PMID- 8550716
TI  - [Chronic osteomyelitis caused by Klebsiella pneumoniae with a 50 year course.
      Medicosurgical management].
AB  - The 50-year clinical course of a case of osteomyelitis of the left tibia is
      reported. Surgical specimens were positive for Klebsiella pneumoniae allowing
      treatment with certriaxone and ciprofloxacine. After antibiotic therapy, regional
      skin expansion was possible with excision and simultaneous closure of a wide area
      of damaged skin resulting from the long-term infection.

PMID- 8550717
TI  - [Intraoperative parathormone assay. The value of assessment of primary
      hyperparathyroidism in surgery].
AB  - Peroperative assay of intact parathormone has been proposed to improve the
      surgical results, either by confirming cure peroperatively or to indicate the
      need for further search in case of persistent pathological secretion. Between
      October 1992 and July 1994 parathormone was assay peroperatively during 136
      operations for primary hyperparathyroidism in 135 patients. Seven samples were
      made for each patient in the operating theatre: at intubation, at skin incision
      (ti), at ablation of the pathological gland, then 15 (t15), 30 (t30) and 60 (t60)
      minutes later. All samples were assayed with the rapid technique and controlled
      the next day with the standard method. The correlation coefficient between the
      two methods was 0.97. Comparing the drop in intact parathormone levels between
      cured patients and those with persistent hyperparathyroidism after surgery showed
      statistically significant differences. We retained a dramatic drop in hormone
      level by 80% between t1 and t15 with persistent low levels between t15 and t30
      (ratio t30 over t15 < 1) as the criteria of cure: the drop off between t1 and t15
      is not sufficient to confirm cure. Peroperative assay of intact parathormone can
      be used to demonstrate the presence of remaining pathological parathyroid tissue,
      especially important in case of highly ectopic localizations. This assay
      technique is not particularly well adapted to routine parathyroid surgery for
      primary hyperthyroidism but has been reserved for cases planned for limited
      dissection (operations conducted under local anaesthesia and reoperations).

PMID- 8550718
TI  - [Kidney traumatism in general surgery (65 cases)].
AB  - From September 1989 to September 1994, 65 patients, 15 females and 50 males, with
      a mean age of 32 +/- 14 years were admitted in the emergency unit for renal
      trauma. In 38.5% of cases multiple trauma was present. Lesional mechanism was
      most frequently contusions (49.2%) and deceleration injuries (43.1%). Gross
      hematuria or microscopic hematuria were presents in 72.3% of cases. The
      sensibility of systematic abdominal echography was 100% in case of perirenal
      hematoma and 65% in case of parenchymatous lesions. Only 23 patients were
      operated (35.3%) because of low blood pressure. None secondary operation was
      necessary in abstention group. Global mortality was 7.7%. Postoperative morbidity
      was 20% and specific morbidity in abstention group was 10.7%.

PMID- 8550719
TI  - [Rupture of a hydatid cyst of the liver into the peritoneal cavity. Value of
      computed tomography].
AB  - The authors report one case of a intraperitoneal rupture of an hydatic cyst. The
      diagnosis of rupture was performed pre-operatively by tomodensitometry which has
      demonstrated the rupture and an intraperitoneal epanchement.

PMID- 8550720
TI  - [Motor deficit complicating an isolated aneurysm of the internal iliac artery].
AB  - A 70-year-old man was admitted to the orthopaedic ward for severe sciatic pain
      and motor deficit. Diagnosis of a unique aneurysm of the right medial iliac
      artery and compression of the neighbouring elements was based on CT scan,
      echography and angiography imaging. This observation emphasizes the importance of
      a through physical examination. Unique aneurysm of the medial iliac artery is
      rarely observed. Effective treatment and satisfactory results can be obtained
      with simple ligature.

PMID- 8550721
TI  - [Retro-cecal hernia].

PMID- 8550722
TI  - The relation between index-finger extension and the acoustic quality of cooing in
      three-month-old infants.
AB  - Fourteen full-term, healthy, three-month-old infants were observed during a total
      of 15 minutes spontaneous face-to-face interaction with their mothers. Facial and
      manual actions, gaze direction and vocalizations were coded. The infants' cooing
      vocalizations were categorized into syllabic and vocalic sounds. Index-finger
      extension occurred frequently in sequence with syllabic sounds, which are speech
      like vocalizations, but rarely occurred in sequence with vocalic sounds. No other
      categories of nonvocal behaviours showed such a relationship. In a subsequent
      experiment, the infants experienced either conversational turn-taking or random
      responsiveness from their mothers. In the turn-taking condition, the infants
      produced a higher ratio of syllabic to vocalic sounds, and a higher frequency of
      index-finger extension. These results suggest a strong connection between speech
      and the pointing gesture long before the infant can actually talk.

PMID- 8550723
TI  - A longitudinal study of infant vocalizations during mother-infant games.
AB  - This study explored the development of verbal behaviours of infants during two
      mother-infant games. Twenty-five infants were videotaped as they played peek-a
      boo and ball with their mothers at 0;6, 0;9, 1;0, 1;3, 1;6, and 2;0. The
      frequencies of eight categories of vocal/verbal behaviours were analysed as they
      evolved over time in both games. Despite differences in the structure and level
      of difficulty of peek-a-boo and ball, the development of these behaviours proved
      to be similar in the two games. One category, PRIMITIVE VOCALIZATIONS, which did
      not change in frequency over time, was seen to have a pragmatic rather than a
      linguistic function. Another category, PRELEXICAL COMMENT, demonstrated an early
      capacity for conveying topic and comment together in the form of speech sounds
      combined with an attention-getting gesture well before the emergence of multiple
      word utterances. The vocal behaviours produced during games were compared with
      the results of language tests administered during the experimental sessions.
      Strong correlations were found between the results of these two measures of
      language. The predictive nature of vocal behaviours during games is discussed.

PMID- 8550724
TI  - Phonetic and phonological contrasts in the acquisition of voicing: voice onset
      time production in Hindi and English.
AB  - The present study examines adult and child word-initial voice onset time
      productions in English and Hindi (10 adults and 20 children in each language) to
      determine the age of acquisition of the phonemic voice contrast. Cross-linguistic
      differences in patterns of acquisition were found, but these need not be traced
      to the different phonological systems per se. An examination of the data
      indicates that the best predictor of age of voice contrast acquisition across
      languages is one which rests on the actual acoustic differences between members
      of phonologically contrastive pairs. In general it was found that the larger the
      post-release voice onset time differences between pair members in the adult
      model, the earlier the contrast is reliably produced by child language learners.

PMID- 8550725
TI  - Phonological awareness in young second language learners.
AB  - English-speaking children (N = 91) who were attending French schools (bilingual
      group) were given a battery of phonological awareness tests in kindergarten and
      in grade I. At the time of kindergarten testing the mean age of the children was
      5:9. Their performance was compared to age-matched English-speaking children (N =
      72) attending English schools (monolingual group). The bilingual children showed
      heightened levels of phonological awareness skills in kindergarten in the area of
      onset-rime awareness. By grade I, the pattern of group differences was more
      complex. The monolingual and bilingual children performed similarly on onset-rime
      segmentation tasks. The monolingual children had higher phoneme awareness scores
      than their French-schooled peers; this result is interpreted to reflect the role
      of literacy instruction on phoneme awareness development. In comparison, the
      bilingual children had higher syllable segmentation scores than their monolingual
      peers. This result is interperted to reflect the role of second language input on
      phonological awareness.

PMID- 8550726
TI  - Early lexical development: the contribution of parental labelling and infants'
      categorization abilities.
AB  - In the present longitudinal study, we examined changes in parental labelling and
      infants' categorization skills as potential predictors of vocabulary composition,
      the age of the naming explosion, and the acquisition of subordinate labels.
      Sixteen French- and English-speaking parent-child dyads were videotaped during a
      20-minute free-play session every month beginning when the child was 1;0 and
      ending at 2;0. The children received object-manipulation tasks every three months
      and their vocabulary growth was recorded. Parental labelling practices were
      assessed monthly using a picture-book reading task. Both parental labelling and
      children's categorization skills predicted the content of children's lexicon,
      with children with more names in their vocabulary having better categorization
      skills. Furthermore, the naming explosion was found to coincide with improvement
      of categorization skills. These findings suggest that the influence of each
      factor varies as a function of the stage and aspect of lexical development
      considered.

PMID- 8550727
TI  - Cross-language synonyms in the lexicons of bilingual infants: one language or
      two?
AB  - This study tests the widely-cited claim from Volterra & Taeschner (1978), which
      is reinforced by Clark's PRINCIPLE OF CONTRAST (1987), that young simultaneous
      bilingual children reject cross-language synonyms in their earliest lexicons. The
      rejection of translation equivalents is taken by Volterra & Taeschner as support
      for the idea that the bilingual child possesses a single-language system which
      includes elements from both languages. We examine first the accuracy of the
      empirical claim and then its adequacy as support for the argument that bilingual
      children do not have independent lexical systems in each language. The
      vocabularies of 27 developing bilinguals were recorded at varying intervals
      between ages 0;8 and 2;6 using the MacArthur CDI, a standardized parent report
      form in English and Spanish. The two single-language vocabularies of each
      bilingual child were compared to determine how many pairs of translation
      equivalents (TEs) were reported for each child at different stages of
      development. TEs were observed for all children but one, with an average of 30%
      of all words coded in the two languages, both at early stages (in vocabularies of
      2-12 words) and later (up to 500 words). Thus, Volterra & Taeschner's empirical
      claim was not upheld. Further, the number of TEs in the bilinguals' two lexicons
      was shown to be similar to the number of lexical items which co-occurred in the
      monolingual lexicons of two different children, as observed in 34 random pairings
      for between-child comparisons. It remains to be shown, therefore, that the
      bilinguals' lexicons are not composed of two independent systems at a very early
      age. Furthermore, the results appear to rule out the operation of a strong
      principle of contrast across languages in early bilingualism.

PMID- 8550728
TI  - The bilingual lexicon: implications for studies of language choice.
AB  - Lexical gaps in vocabulary development have been acknowledged as a reason for
      language mixing in young bilingual children. In spite of this, most studies do
      not take into account whether young bilinguals have the lexical resources to make
      a choice between their two languages. Inferences are nevertheless still being
      made about whether or not young bilinguals differentiate between their two
      languages based on language choice. It is widely believed, however, that young
      bilinguals do not have the resources to make lexical choices at a pre-syntactic
      stage of development before age two. A bilingual case study of an infant
      acquiring Spanish and English from birth to age 1;10 is used to address this
      issue. Daily diary records and weekly video recordings in the two language
      contexts are used to construct the child's lexicon and to establish that
      translation equivalents that make possible language choice are available from the
      beginning of speech. The results are used to discuss the importance of
      translation equivalents in the bilingual lexicon for viable interpretations of
      language choice.

PMID- 8550729
TI  - Relative clauses are barriers to wh-movement for young children.
AB  - Two studies are described which investigate preschool children's sensitivity to
      relative clauses as barriers to the movement of wh-questions. The children were
      presented with short stories followed by questions in which the wh-word had two
      possible sites of interpretation, the ungrammatical option being inside a
      relative clause. A cross-sectional study with 23 children aged 3;1 to 6;1, and a
      longitudinal study over the course of one year with 12 children aged 3;1 to 4;1
      at the start, found young children refused to extract wh-questions from the
      ungrammatical site inside a relative clause. This confirms other findings that
      children's early grammars are sensitive to universal constraints on movement. In
      addition, the children differentiated between wh-complements and relative clauses
      in their tendency to mistakenly answer the medial wh-complementizer but not the
      wh-relative pronoun. Explanations for the latter are framed in terms of
      children's initial assumptions about the attachment of complements.

PMID- 8550730
TI  - The use of props in a syntactic awareness task.
AB  - The study investigated the effects of using props to illustrate the meaning of
      sentences in a syntactic awareness task in which subjects were required to
      correct ungrammatical sentences. Forty preschool children (aged 4; 11 to 5; 11)
      were asked to correct 20 sentences, 10 of which were illustrated using props, and
      10 of which were not. Children scored significantly higher in the props condition
      though the proportion of meaning-changing errors to total errors was not
      significantly lower in this condition. It is argued that the use of props, by
      providing contextual support, reduces the processing capacity required to
      complete the task.

PMID- 8550731
TI  - Rice balls and bear hunts: Japanese and North American family narrative patterns.
AB  - In past research, the form of Japanese children's personal narratives was found
      to be distinctly different from that of English-speaking children. Despite follow
      up questions that encouraged them to talk about one personal narrative at length,
      Japanese children spoke succinctly about collections of experiences rather than
      elaborating on any one experience in particular (Minami & McCabe, 1991).
      Conversations between mothers and children in the two cultures were examined in
      order partly to account for the way in which cultural narrative style is
      transmitted to children. Comparison of mothers from the two cultures yielded the
      following salient contrasts: (1) In comparison to the North American mothers, the
      Japanese mothers requested proportionately less description from their children.
      (2) Both in terms of frequency and proportion, the Japanese mothers gave less
      evaluation and showed more verbal attention to children than did North American
      mothers. (3) Japanese mothers pay verbal attention more frequently to boys than
      to girls. In addition, at five years, Japanese children produce 1.22 utterances
      per turn on average, while North American children produce 2.00 utterances per
      turn, a significant difference. Thus, by frequently showing verbal attention to
      their children's narrative contributions, Japanese mothers not only support their
      children's talk about the past but also make sure that it begins to take the
      shape of narration valued in their culture. The production of short narratives in
      Japan is understood and valued differently from such production in North America.

PMID- 8550732
TI  - Children's overregularization of English plurals: a quantitative analysis.
AB  - This paper brings a quantitative study of children's noun plural
      overregularizations (foots, mans) to bear on recent comparisons of connectionist
      and symbolic models of language. The speech of 10 English-speaking children (aged
      1;3 to 5;2) from the CHILDES database (MacWhinney & Snow, 1985, 1990) were
      analysed. The rate of noun overregularization is low, mean = 8.5%, demonstrating
      that children prefer correct to overregularized forms. Rates of noun
      overregularization are not significantly different from their rates of past tense
      overregularization, and noun plurals, like verb past tenses, follow a U-shaped
      developmental curve in which correct irregulars precede the first overregularized
      forms. These facts suggest that plural and past tense overregularizations are
      caused by similar underlying processes. The results pose challenges to
      connectionist models, but are consistent with Marcus et al.'s (1992) blocking-and
      retrieval-failure model in which regulars are generated by a default rule while
      irregulars are retrieved from the lexicon.

PMID- 8550733
TI  - Early lexical acquisition and the vocabulary spurt: a response to Goldfield &
      Reznick.
AB  - Vocabulary development of three children (aged 1;6-1;8 at the start of the study)
      who had not begun to evidence a vocabulary spurt even though their productive
      vocabularies already included well over 50 words was followed to determine if
      these children eventually would have a vocabulary spurt. All three children
      evidenced a spurt, beginning at a mean productive vocabulary size of 112 words.
      The vocabulary spurt occurred at about the same time as the children first
      demonstrated the ability to sort objects exhaustively and to fast map new object
      names. Results are discussed in the context of Goldfield & Reznick's (1990;
      Reznick & Goldfield, 1992) argument that a substantial proportion of children
      never evidence a vocabulary spurt.

PMID- 8550734
TI  - Clinical review 76: The nature of osteoporosis.

PMID- 8550735
TI  - Infradian rhythms in urinary growth hormone excretion.
AB  - All studies of urinary GH excretion in normal and disordered growth have revealed
      marked day to day (infradian) variation. We used serial overnight urinary GH
      estimations as an indirect measure of endogenous GH secretion in eight normal
      prepubertal children (aged 3.6-7.3 yr) over 90-365 days to determine whether
      longer term rhythms in GH output could exist. This study constitutes a first step
      in examining the potential relationship between GH excretion and growth. Urinary
      GH was measured by immunoradiometric assay after dialysis, expressed as the total
      amount excreted (nanograms per night) or as the GH/creatinine ratio (nanograms
      per mmol), and assessed by pulse counting techniques and time-series analysis.
      Variability in urinary GH excretion (median coefficient of variation, 46%) was
      significantly greater than creatinine (median coefficient of variation, 25%; P =
      0.003). Additionally, there was marked month by month variation in baseline
      urinary GH in all children. High frequency pulses of urinary GH were defined in
      all children, with periods between 3-5 days. In the two children followed for 7
      months or more, time-series analysis was also undertaken on urinary GH data
      divided into weekly series. This revealed significant rhythms present at 2.6 and
      4.1 weeks. There were, therefore, three components to urinary GH excretion: long
      term basal fluctuation (over months), short term pulses (over days), and
      intermediate rhythms (over weeks). Further work is required to establish the
      relationship between these patterns of GH excretion and short term growth.

PMID- 8550736
TI  - Effects of thrombin on steroid-modulated cultured endometrial stromal cell
      fibrinolytic potential.
AB  - By virtue of their unique chronic expression of tissue factor, the primary
      initiator of hemostasis, decidualized endometrial stromal cells are capable of
      significant thrombin generation after vascular disruption. In addition to its
      potent procoagulant effects, thrombin modifies endothelial and glomerular cell
      fibrinolytic activity. Therefore, we evaluated whether thrombin affected the
      expression of endometrial stromal cell urokinase-type (uPA) and tissue-type (tPA)
      plasminogen activators and their primary inhibitor, type 1 plasminogen activator
      inhibitor (PAI-1), and whether ovarian steroids modulated putative thrombin
      effects. Confluent stromal cell cultures were incubated in a defined medium
      containing vehicle control, 10(-8) mol/L estradiol (E2), 10(-7) mol/L
      medroxyprogesterone acetate (MPA), or E2 plus MPA for 4 days. The medium was then
      collected and exchanged for medium containing the corresponding steroids with or
      without thrombin and the specific thrombin inhibitor, D-phenyl-alanyl-propyl
      arginine-chloromethyl ketone, for an additional 24 h. The conditioned medium was
      then collected and analyzed for immunoreactive (ir) uPA, tPA, and PAI-1 by enzyme
      linked immunosorbent assay and for PA activity by chromogenic assay, whereas
      Northern analysis of the cells was employed to evaluate the expression of
      thrombin receptor, uPA, tPA, and PAI-1 messenger ribonucleic acid (mRNA) species.
      The latter studies revealed that confluent cultures incubated in defined medium
      expressed the 3.45-kilobase thrombin receptor message. Steady state levels of
      thrombin receptor mRNA were unaffected by exogenous steroids. Thrombin added in
      the absence of exogenous steroids elevated concentrations of ir tPA, uPA, and PAI
      1 compared with control cultures. Conversely, in the absence of added thrombin,
      MPA added alone or together with E2 inhibited levels of ir tPA and uPA while
      stimulating PAI-1 levels despite the lack of a response to E2 alone.
      Interestingly, thrombin counteracted this progestin inhibition of tPA and uPA
      expression and augmented the progestin-enhanced expression of PAI-1. Northern
      analysis revealed that steady state levels of tPA and uPA mRNA were also enhanced
      by thrombin in both control and steroid-containing cultures. Net PA activity
      reflects the balance between PA and PAI-1. In the absence of thrombin, there is
      virtually no detectable tPA activity and minimal uPA activity in progestin
      exposed cultures. However, thrombin elicited significant increases in tPA and uPA
      activity in control and E2-treated cultures. Despite the molar excess of PAI-1 in
      MPA-treated and E2- plus MPA-treated cultures, thrombin reversed progestin
      inhibition of PA activity. Predictably, the addition of D-phenyl-alanyl-propyl
      arginine-chloromethyl ketone, blocked the effects of thrombin on PAI-1, tPA, and
      uPA protein and mRNA expression and PA activity. In summary, thrombin enhances
      endometrial stromal cell fibrinolytic and extracellular matrix-degrading protease
      activity in vitro. Such processes occurring in vivo would probably play a role in
      menstruation and abnormal uterine bleeding.

PMID- 8550737
TI  - Permissive role of polyamines in the cooperative action of estrogens and insulin
      or insulin-like growth factor I on human breast cancer cell growth.
AB  - Polyamines have been proposed as specific mediators of estrogen action in breast
      cancer cells, but their exact role in this process is still controversial. As
      estrogens cooperatively interact with peptide growth factors in several hormonal
      responses, the involvement of polyamines in the synergistic effect of 17 beta
      estradiol (E2) and insulin or insulin-like-growth factor I (IGF-I) on cell
      growth, polyamine pools, specific gene induction, and cell cycle progression was
      examined in estrogen-responsive MCF-7 and ZR-75-1 human breast cancer cells.
      Spermidine depletion induced by the ornithine decarboxylase inhibitor, alpha
      difluoromethylornithine (DFMO), resulted in complete cytostasis and loss of
      mitogenic response to either E2 or insulin (or IGF-I). In contrast, a steroidal
      antiestrogen blocked the mitogenic effect of E2, but only partly interfered with
      the synergistic stimulation of estrogen action by insulin. Whereas antiestrogen
      resistant growth in insulin-treated cells was halted by DFMO, the antiestrogen
      did not further inhibit growth upon prior polyamine depletion. E2 and either IGF
      I or insulin induced early increases in putrescine and spermidine, but not
      spermine, contents in both MCF-7 and ZR-75-1 cells. Moreover, spermidine
      depletion and decarboxylated S-adenosylmethionine accumulation induced by DFMO
      required prior mitogenic stimulation by E2 and/or IGF-I. The antiestrogen alone
      had only a limited effect on polyamine and nucleoside pools. DFMO did not
      interfere with the coordinate induction of the estrogen- and growth factor
      inducible pS2 messenger ribonucleic acid by E2 and insulin even after a 5-day
      treatment with the drug. On the other hand, DFMO depressed the cycling fraction
      of E2/IGF-I-stimulated MCF-7 cell population far more dramatically than the
      antiestrogen and to less than that noted in mitogen-deprived cells. However, in
      ZR-75-1 cells, which have a much lower spermidine/spermine ratio than MCF-7
      cells, specific inhibition of spermine synthase selectively antagonized the
      effect of E2 compared with that of insulin. These data indicate that spermidine
      has a permissive role for macromolecular synthesis and cell cycle traverse, but
      does not qualify as a limiting factor in estrogen receptor-mediated events per se
      in breast cancer cells. Moreover, polyamine depletion is an efficient
      complementary strategy to block the mitogenic action of peptide growth factors,
      which is only partly antagonized by antiestrogens.

PMID- 8550738
TI  - Nelson's syndrome associated with a somatic frame shift mutation in the
      glucocorticoid receptor gene.
AB  - Nelson's syndrome is the appearance and/or progression of ACTH-secreting
      pituitary macroadenomas in patients who had previously undergone bilateral
      adrenalectomy for Cushing's disease. Extremely high plasma ACTH levels and
      aggressive neoplastic growth might be explained by the lack of appropriate
      glucocorticoid negative feedback due to defective glucocorticoid signal
      transduction. To study the glucocorticoid receptor (GR) gene in Nelson's
      syndrome, DNA was extracted from pituitary adenomas and leukocytes of four
      patients with this condition and amplified by PCR for direct sequence analysis.
      In one of the tumors, a heterozygous mutation, consisting of an insertion of a
      thymine between complementary DNA nucleotides 1188 and 1189, was found in exon 2.
      This frame-shift mutation led to premature termination at amino acid residue 366
      of the wild-type coding sequence, excluding the expression of a functioning
      receptor protein from the defective allele. The mutation was not detected in the
      sequence of the GR gene in the patient's leukocyte DNA, indicating a somatic
      origin. By lowering the receptor number in tumorous cells, this defect might have
      caused local resistance to negative glucocorticoid feedback similar to that
      caused by the presence of a null allele in a kindred with the generalized
      glucocorticoid resistance syndrome. P53 protein accumulation, previously reported
      in 60% of corticotropinomas, could not be detected in any of the four pituitary
      tumors examined by immunohistochemistry. We suggest that a somatic GR defect
      might have played a pathophysiological role in the tumorigenesis of the
      corticotropinoma bearing this mutation.

PMID- 8550739
TI  - Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3
      deficiency.
AB  - Autosomal recessive mutations in the 17 beta-hydroxysteroid dehydrogenase 3 gene
      impair the formation of testosterone in the fetal testis and give rise to genetic
      males with female external genitalia. Such individuals are usually raised as
      females, but virilize at the time of expected puberty as the result of increases
      in serum testosterone. Here we describe mutations in 12 additional
      subjects/families with this disorder. The 14 mutations characterized to date
      include 10 missense mutations, 3 splice junction abnormalities, and 1 small
      deletion that results in a frame shift. Three of these mutations have occurred in
      more than 1 family. Complementary DNAs incorporating 9 of the 10 missense
      mutations have been constructed and expressed in reporter cells; 8 of the 9
      missense mutations cause almost complete loss of enzymatic activity. In 2
      subjects with loss of function, missense mutations testosterone levels in
      testicular venous blood were very low. Considered together, these findings
      strongly suggest that the common mechanism for testosterone formation in
      postpubertal subjects with this disorder is the conversion of circulating
      androstenedione to testosterone by one or more of the unaffected 17 beta
      hydroxysteroid dehydrogenase isoenzymes.

PMID- 8550740
TI  - Amniotic fluid insulin and C peptide levels in diabetic and nondiabetic women
      during early pregnancy.
AB  - Thanks to the widespread use of amniocentesis, glucose, insulin, and C peptide
      have often been measured in amniotic fluid (AF) during late gestation, but little
      is known about their concentrations during early pregnancy. To better understand
      early fetal beta-cell function under normal conditions and in the presence of
      maternal diabetes, we measured glucose, insulin, and C peptide in the AF
      collected during weeks 15-22 in 77 healthy and 9 diabetic women undergoing
      amniocentesis for clinical indications and compared the results with those
      obtained during late pregnancy (weeks 34-36). The AF C peptide concentration was
      higher in diabetic women (102 +/- 53 vs. 38 +/- 2 pmol/L), in the women with a
      family history of diabetes (41 +/- 6 vs. 35 +/- 2 pmol/L), after the 19th week of
      gestation (46 +/- 5 vs. 35 +/- 2 pmol/L; in the presence of lower glucose
      concentrations), and in the presence of maternal plasma glucose levels greater
      than 5.56 mmol/L (42 +/- 3.5 vs. 34 +/- 2 pmol/L). The comparison between early
      and late gestation showed decreasing glucose and increasing C peptide
      concentrations in both healthy and diabetic women (in the latter, C peptide
      values were always 3 times higher), whereas the insulin concentration was
      increased in late gestation only in diabetic women. The AF C peptide/insulin
      molar ratio increased throughout pregnancy in both healthy (from 0.97 +/- 0.06 to
      4.3 +/- 1.2) and diabetic (from 2.9 +/- 1.1 to 13.2 +/- 1.6) women. These
      parallel changes suggest that the fetal clearance and/or degradation of insulin
      and C peptide may greatly change during both normal and diabetic gestation.

PMID- 8550741
TI  - Genetic influence on bone turnover in postmenopausal twins.
AB  - Postmenopausal bone mass is determined by both peak bone mass and subsequent bone
      loss. Previous studies have shown that peak bone mass is under genetic influence
      mediated partly by factors affecting bone formation. The rate of bone loss
      increases markedly after the menopause, but is highly variable from subject to
      subject. The aims of this study were to determine whether postmenopausal bone
      turnover was under genetic control, which should be linked to the genetic
      influence on the rate of postmenopausal bone loss. A classical twin study was
      performed that compared the intraclass correlations in monozygotic (MZ) twins
      with those in dizygotic (DZ) twins, with any difference assumed to be due to
      genetic factors. Markers of bone formation and resorption were measured in 240
      untreated postmenopausal twins, aged 45-69 yr, on the average 12.3 yr (SD, 6.0)
      postmenopause, including 61 MZ pairs and 59 DZ pairs. The intraclass correlation
      coefficient of MZ twin pairs, rMZ (95% confidence interval), for 2 specific
      markers of bone formation, serum osteocalcin and bone-specific alkaline
      phosphatase, were higher than the corresponding rDZ [0.67 (range, 0.59-0.75) vs.
      0.48 (range, 0.35-0.61; P = 0.06) for osteocalcin and 0.53 (range, 0.41-0.65) vs.
      0.21 (range, 0.01-0.41; P = 0.02) for bone-specific alkaline phosphatase]. For
      serum propeptide of type I collagen, a type I collagen synthesis marker that
      exhibits only a slight increase after menopause, a high proportion of its
      variance was explained by genetic factors [rMZ = 0.82 (0.77-0.87), rDZ = 0.33
      (0.16-0.50); P < 0.001]. The correlations for bone resorption measured by three
      distinct urinary markers, total deoxypyridinoline and two cross-linked type I
      collagen peptides (CrossLaps and NTX), that increase markedly after menopause
      were higher in MZ than in DZ pairs, but the difference reached significance only
      for NTX (P = 0.03). For urinary free dexoypyridinoline, a marker reflecting bone
      collagen degradation that increases moderately after menopause, the proportion of
      the variance explained by genetic factors was highly significant (P = 0.002). In
      conclusion, our data indicate that a proportion of the variance in postmenopausal
      levels of both bone formation and resorption markers are explained by genetic
      factors, but this contribution was clearly significant only for markers that do
      not change markedly at the menopause. These data suggest that the contribution of
      genetic factors to overall postmenopausal bone turnover and possibly bone loss is
      likely to be small.

PMID- 8550742
TI  - Familial pheochromocytoma associated with a novel mutation in the von Hippel
      Lindau gene.
AB  - We report a three generation, 25 member kindred with familial pheochromocytoma.
      Seven subjects of generations I and II had pheochromocytoma, in five of the
      seven, the tumors were bilateral, and in two of the seven, the tumors were both
      adrenal and extraadrenal. One patient also had a carotid body chemodectoma, and
      one patient had a malignant adrenal tumor and abdominal paraganglioma. In the
      patient with the chemodectoma, a cerebellar hemangioblastoma became manifest 25
      yr after his initial diagnosis with pheochromocytoma, leading only then to a
      clinical diagnosis of von Hippel-Lindau disease (VHL). A mutational analysis of
      the VHL gene revealed a novel nucleotide 709 G-->T transversion present in all
      affected subjects and in four presymptomatic children. In familial
      pheochromocytoma the diagnosis of VHL should be considered, even when the formal
      criteria for diagnosis of the syndrome are lacking.

PMID- 8550743
TI  - Pregnancy-induced Cushing's syndrome in multiple pregnancies.

PMID- 8550744
TI  - Identification and characterization of insulin-like growth factors (IGFs), IGF
      binding proteins (IGFBPs), and IGFBP proteases in human synovial fluid.
AB  - The insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) in human
      synovial fluid play an important role in maintaining articular cartilage
      metabolism. In this study we measured the concentrations of IGF-I, IGF-II, and
      IGFBP-3 in normal human synovial fluid by RIA and characterized the IGFBPs by
      Western ligand blot (WLB), Western immunoblot, and immunoprecipitation. We also
      extended the study and compared normal synovial fluid to synovial fluids from
      patients with osteoarthritis (OA) and rheumatoid arthritis (RA). The
      concentrations of IGF-I, IGF-II, and IGFBP-3 in normal synovial fluid were 19 +/-
      3 (mean +/- SE), 194 +/- 14, and 349 +/- 65 ng/mL, respectively. In synovial
      fluid of patients with OA, IGF-I levels were elevated, whereas IGF-II was
      decreased, and the IGFBP-3 level was similar to the control value. In patients
      with RA, both IGF-I and IGFBP-3 were elevated, whereas IGF-II remained unchanged.
      WLB and immunoprecipitation of normal synovial fluid revealed IGFBP-1 (26-29
      kDa), IGFBP-2 (32 kDa), IGFBP-3 (42- to 39-kDa doublet), and IGFBP-4 (24 kDa);
      the IGFBP-3 doublet was very faint. In RA synovial fluid, all IGFBPs were
      dramatically increased, whereas little change was seen in the synovial fluid of
      OA. Western immunoblot against IGFBP-3 revealed a prominent 30-kDa immunoreactive
      fragment of IGFBP-3 in synovial fluids of normal adults as well as in those of RA
      and OA patients. This was concurrent with detectable IGFBP-3 protease activity,
      which was characterized to be of the metallo- and serine protease family. Thus,
      in normal synovial fluid, there is a balance of circulating IGF, IGFBP, and
      proteases to modulate the bioactivity of IGF. In pathological states, the
      increased IGF-I concentrations were accompanied by an increase in IGFBP-I
      concentrations were accompanied by an increase in IGFBP-3 levels in synovial
      fluid. These findings suggest that alteration of the IGF and IGFBP axis in
      pathological states may be important for understanding the underlying
      pathophysiology of disordered articular growth and metabolism.

PMID- 8550745
TI  - Changes in plasma phosphate levels influence insulin sensitivity under euglycemic
      conditions.
AB  - The euglycemic clamp technique is a useful tool to evaluate insulin-mediated
      glucose uptake. The plasma phosphate concentration decreases during euglycemic
      clamp studies. Because insulin-dependent glucose uptake is closely related to
      phosphate uptake, we investigated whether modulation of plasma phosphate levels
      in the range observed during clamp studies influences insulin sensitivity. We
      studied 11 healthy (phosphate-replete) male volunteers (mean age, 27.5 +/- 1.8
      yr;, mean body mass index, 23.9 +/- 1.6 kg/m2) in a double blind placebo
      controlled cross-over study. The volunteers received in random order on two
      occasions either an infusion of sodium chloride (sham infusion) or an infusion of
      sodium phosphate. Insulin sensitivity was assessed under euglycemic conditions
      (clamp technique). The mean plasma phosphate concentration decreased with sham
      infusion from 1.09 +/- 0.17 to 0.64 +/- 0.13 mmol/L, whereas it increased with
      phosphate infusion from 1.06 +/- 0.19 to 1.32 +/- 0.13 mmol/L. In all volunteers
      except one the glucose disposal rate (M-value) was higher after phosphate
      infusion (mean M-value, 10.4 +/- 1.5 mg/kg.min) than that after sham infusion
      (mean M-value, 9.4 +/- 1.5 mg/kg.min; P < 0.01, by Wilcoxon's test for paired
      samples). There were no significant differences in mean plasma glucose, sodium,
      insulin, or arterialized standard bicarbonate levels with the two infusion
      protocols. Mean plasma calcium, albumin-corrected calcium, and potassium levels,
      however, were all significantly (P < 0.05) lower after phosphate infusion than
      after sham infusion. The mean PTH level decreased with sham infusion from 28 +/-
      9 to 20 +/- 6 ng/L, whereas it increased with phosphate infusion from 26 +/- 9 to
      36 +/- 8 ng/L, whereas it increased with phosphate infusion from 26 +/- 9 to 36
      +/- 8 ng/L. The difference between the two infusion protocols was statistically
      significant (P < 0.01). The data presented illustrate that plasma phosphate (and
      calcium) levels may be confounders that should be at least monitored, and
      possibly controlled for, when performing euglycemic clamp studies.

PMID- 8550746
TI  - Sequential changes in insulin-like growth factor I (IGF-I) and IGF-binding
      proteins in children with end-stage liver disease before and after successful
      orthotopic liver transplantation.
AB  - Pediatric end-stage liver disease (ESLD) leads to poor linear growth and wasting.
      After orthotopic liver transplantation (OLT), catch-up growth occurs
      unpredictably and with a delay. The bulk of circulating insulin-like growth
      factor I (IGF-I) and its major circulating binding protein, IGF-binding protein-3
      (IGFBP-3), is derived from the liver. We hypothesized that growth failure in
      ESLD, both before and after OLT, may result from abnormalities in the IGF-IGFBP
      axis. Serum IGF-I, IGFBP-1, and insulin were measured by RIA, and IGFBP-3 was
      determined by immunoradiometric assay in 26 children with ESLD (mean of 3.7
      samples pre-OLT and 4.2 samples post-OLT per patient) and 30 age-matched
      controls. In addition, serum IGFBPs were visualized by Western ligand blotting.
      IGFBP-3 and IGFBP-2 were also observed by immunoblotting with specific antisera.
      IGFBP-3 protease activity was determined by protease gels using recombinant human
      IGFBP-3 label as substrate. Anthropometric measurements were performed according
      to standard techniques. Pre-OLT, IGF-I (32.7 +/- 4.8 micrograms/L), and IGFBP-3
      (1.11 +/- 0.10 mg/L) were significantly lower than control values [IGF-I, 168.3
      +/- 16.5 micrograms/L (P = 0.0001); IGFBP-3, 2.57 +/- 0.17 mg/L (P = 0.0001)].
      Post-OLT, IGF-I (179.2 +/- 19.7 micrograms/L; P = NS) rose to control levels,
      whereas IGFBP-3 (3.49 +/- 0.14 mg/L; P = 0.002) became significantly greater than
      the control value. IGFBP-1 was significantly higher pre-OLT (78.9 +/- 9.6
      micrograms/L; P = 0.0001) than post-OLT (45.7 +/- 6.9 micrograms/L), and both
      were significantly higher than control values (18.5 +/- 2.5 micrograms/L; P =
      0.0001 vs. pre-OLT and P = 0.0002 vs. post-OLT). There was a trend toward higher
      insulin levels both pre-OLT (15.5 +/- 1.8 mU/L) and post-OLT (12.5 +/- 1.4 mU/L)
      compared with control values (9.7 +/- 1.1 mU/L; P = 0.06 vs. pre-OLT). IGFBP-1
      was negatively correlated with serum insulin post-OLT (P = 0.008), but there was
      no correlation pre-OLT. Western ligand blotting confirmed the changes in IGFBP-3
      pre- and post-OLT. Immunoblotting demonstrated a reduction in all mol wt forms of
      IGFVBP-3 pre-OLT. Protease assays demonstrated the appearance of IGFBP-3
      proteolysis only at a time coincidental with the operative stress of OLT;
      overall, there was no difference in protease activity pre- and post-OLT. IGFBP-2
      was unchanged post-OLT compared with pre-OLT, although levels were higher than
      control values. Mid-upper arm circumference and triceps skin fold thickness SD
      score 3 months post-OLT and weight SD score 1 yr post-OLT were significantly
      higher than those at OLT. In conclusion, IGF-I and IGFBP-3 are reduced, and IGFBP
      1 and IGFBP-2 are increased in children with ESLD. After OLT, IGF-I levels return
      to normal, but marked abnormalities in IGFBPs remain. These changes may help to
      explain at least in part the growth failure seen in pediatric ESLD both before
      and after successful OLT.

PMID- 8550747
TI  - Pituitary adenylate-cyclase activating peptide enhances aldosterone secretion of
      human adrenal gland: evidence for an indirect mechanism, probably involving the
      local release of catecholamines.
AB  - Evidence is accumulating that the adrenal medulla exerts a paracrine control on
      the secretory activity of the cortex by releasing catecholamines and several
      regulatory peptides. Pituitary adenylate-cyclase activating peptide (PACAP) is
      contained in the adrenal medulla of several mammalian species and in human
      pheochromocytomas. Thus, we investigated whether PACAP exerts a modulatory action
      on steroid secretion by the human adrenal cortex in vitro. Adrenal slices
      (including both capsule and medulla) and dispersed adrenocortical cells (obtained
      from the gland tail deprived of medulla) were employed. Both adrenal preparations
      secreted aldosterone (ALDO) and cortisol in response to 10 nmol/L ACTH. PACAP (10
      nmol/L) was found to enhance basal ALDO production by adrenal slices, but not by
      dispersed cells. PACAP was ineffective on cortisol secretion of both
      preparations. Adrenal slices displayed a marked ALDO, but not cortisol, secretory
      response to 100 nmol/L isoprenaline or noradrenaline. l-Alprenolol (1 mumol/L), a
      specific beta-adrenoceptor antagonist, completely suppressed the ALDO response to
      both beta-adrenoceptor agonists and 10 nmol/L PACAP, without per se altering
      basal ALDO output by adrenal slices. PACAP (10 nmol/L) induced a net rise in
      catecholamine release by adrenal slices. Taken together, our present findings
      suggest that PACAP indirectly stimulates ALDO secretion by the human adrenal
      cortex, probably by eliciting the local release of catecholamines by medullary
      chromaffin cells that are also scattered in the cortical tissue, especially the
      zona glomerulosa.

PMID- 8550748
TI  - Aromatase expression in endometriosis.
AB  - The conversion of C19 steroids to estrogens occurs in a number of tissues, such
      as the ovary and placenta, and is catalyzed by aromatase P450 (P450arom; the
      product of the CYP19 gene). P450arom expression has also been detected in a
      number of uterine tumors, such as leiomyomas and endometrial cancer. On the other
      hand, P450arom expression was undetectable in normal endometrial and myometrial
      tissues. The present study was conducted to determine the presence or absence of
      aromatase expression in peritoneal endometriotic implants and in the eutopic
      endometrium of women with endometriosis. Endometriotic implants in pelvic
      peritoneum (n = 17; e.g. posterior culdesac, bladder, and anterior culdesac) and
      eutopic endometrial curettings (n = 11) of 14 patients with histologically
      documented pelvic endometriosis were obtained at the time of laparoscopy or
      laparotomy. Pelvic peritoneal biopsies distal to endometriotic implants as well
      as normal endometrial tissues (n = 7) from disease-free women were used as
      negative controls. We used competitive RT-PCR technology employing an internal
      standard to amplify P450arom transcripts in total ribonucleic acid (RNA) isolated
      from these tissues. P450arom transcripts were detected in all endometriotic
      implants and in all eutopic endometrial tissues from patients with endometriosis.
      P450arom messenger RNA species were not detectable in endometrial tissues from
      disease-free women or in endometriosis-free peritoneal tissues. The highest
      levels of transcripts were detected in an endometriotic implant that involved the
      full thickness of the anterior abdominal wall. The P450arom transcript level
      within the core of this endometriotic mass was 4-fold higher than that in the
      surrounding adipose tissue. It has been shown recently that aromatase expression
      in various human tissues is regulated by the use of tissue-specific promoters via
      alternative splicing. To analyze promoter usage, we amplified by RT-PCR the most
      likely promoter-specific untranslated 5'-termini of P450arom transcripts in 2
      endometriotic implants. It appears that these endometriotic implants use both the
      adipose-type promoter I.4 and gonadal-type promoter II for aromatase expression.
      The use of promoter I.4 for aromatase expression in adipose tissue has been
      recently observed to be regulated by members of the interleukin-6 (IL-6) cytokine
      family. Based on these findings, we examined by RT-PCR, IL-6 and IL-11 messenger
      RNA expression in 5 endometriotic tissues and 1 eutopic endometrial sample from a
      patient with endometriosis. We detected IL-6 and IL-11 transcripts in all
      endometriotic tissues and in the eutopic endometrial tissue sample studied. Our
      findings indicate that both eutopic endometrial tissues and endometriotic
      implants from patients with endometriosis are biochemically different from normal
      endometrial tissues of disease-free women. The presence of aromatase expression
      in eutopic endometrial tissues from patients with endometriosis may be related to
      the capability of implantation of these tissues on peritoneal surfaces.
      Furthermore, the possibility of estrogen production in these implants may serve
      to promote their growth. Increased IL-6 and IL-11 expression in these tissues
      suggests that P450arom expression in endometriosis may be regulated in part by
      these cytokines.

PMID- 8550749
TI  - Plasma adrenomedullin concentration in patients with heart failure.
AB  - We measured plasma concentrations of adrenomedullin (AM), a novel bioactive
      peptide with potent vasodilator activity, in 21 patients with chronic congestive
      heart failure due to various heart diseases and compared them to levels in age-
      and sex-matched healthy subjects to examine the pathophysiological role of plasma
      AM in heart failure. In addition, the relationship between plasma AM and other
      hormones known to control the cardiovascular system was examined in these
      patients. The plasma AM level in the patients with heart failure was
      significantly (P < 0.01) higher than that in the control subjects (mean +/- SEM,
      2.94 +/- 0.15 fmol/mL; n = 16), with a significantly (P < 0.05) higher
      concentration in patients in class III or IV (11.82 +/- 1.81 fmol/mL; n = 5) of
      the New York Heart Association functional classification than in those in class I
      or II (8.74 +/- 0.44 fmol/mL; n = 16). There were no significant correlations
      between plasma AM and catecholamine levels, whereas the plasma AM level was
      significantly correlated with the concentrations of plasma atrial natriuretic
      peptide (r = 0.58; P < 0.01), brain natriuretic peptide (r = 0.47; P < 0.05), and
      PRA (r = 0.77; P < 0.01) in the patients. Thus, the plasma AM concentration
      increased in proportion to the severity of heart failure along with the hormones
      known to modulate the development of congestive heart failure. The present
      findings suggest a possible role for AM as a circulating hormone participating in
      the defense mechanism against further deterioration of congestive heart failure
      in patients with heart disease.

PMID- 8550750
TI  - Short-term neuroendocrine effects of a large oral dose of monosodium glutamate in
      fasting male subjects.
AB  - Fasting male subjects received each of four treatments on different days: a large
      oral dose of monosodium L-glutamate (MSG; 12.7 g), the MSG vehicle, an iv
      injection of TRH, or a high protein meal. Blood samples were drawn via an
      indwelling venous line before and at 20-min intervals after each treatment for 4
      h. Plasma glutamate levels rose 11-fold within 1 h of MSG ingestion, but did not
      change appreciably with any of the other treatments. Plasma PRL levels rose 10
      fold after TRH infusion and 2-fold after the protein meal, but did not rise
      significantly after MSG ingestion. No effects resulted from any of the treatments
      on plasma LH, FSH, testosterone, GH, or cortisol concentrations. Plasma levels of
      TSH, T4, and T3 showed minimal changes after any of the treatments except TRH;
      TRH elevated plasma TSH and T3 levels. Self-rating instruments of mood and side
      effects revealed no treatment-related effects on mood or physical state for up to
      48 h after each treatment. Together, these results suggest that acute
      pharmacological elevations of plasma glutamate levels in adult men produce
      minimal, if any, effects on hypothalamic or pituitary function.

PMID- 8550751
TI  - A novel point mutation in the translation initiation codon of the pre-pro
      vasopressin-neurophysin II gene: cosegregation with morphological abnormalities
      and clinical symptoms in autosomal dominant neurohypophyseal diabetes insipidus.
AB  - Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare variant
      of idiopathic central diabetes insipidus. Several different mutations in the
      human vasopressin-neurophysin II (AVP-NP II) gene have been described. We studied
      nine family members from three generations of an ADNDI pedigree at the clinical,
      morphological, and molecular levels. AVP concentrations were measured during
      diagnostic fluid restriction tests. Coronal and sagittal high resolution T1
      weighted images of the pituitary were obtained from affected and healthy family
      members. PCR was used to amplify the AVP-NP II precursor gene, and PCR products
      were directly sequenced. Under maximal osmotic stimulation, AVP serum levels were
      close to or below the detection limit in affected individuals. Magnetic resonance
      imaging studies revealed the characteristic hyperintense ("bright spot")
      appearance of the posterior pituitary in two healthy family members. This signal
      was absent in all four ADNDI patients examined. The coding sequences of AVP and
      its carrier protein, neurophysin II, were normal in all family members examined.
      Affected individuals showed a novel single base deletion (G 227) in the
      translation initiation codon of the AVP-NP II signal peptide on one allele. The
      mutation in the AVP-NP II leader sequence appears to be responsible for the
      disease in this kindred, possibly by interfering with protein translocation. The
      absence of the hyperintense posterior pituitary signal in affected individuals
      could reflect deficient posterior pituitary function.

PMID- 8550752
TI  - Parathyroid hormone (PTH)-related protein(1-36) is equipotent to PTH(1-34) in
      humans.
AB  - Humoral hypercalcemia of malignancy (HHM) results from the production of PTH
      related protein (PTHrP) by human tumors. One previous study has reported the
      results of human (h) PTHrP(1-34) infusion into humans. In that report, hPTHrP(1
      34) was found to be qualitatively similar to but 3- to 10-fold less potent than
      hPTH(1-34). Because hPTHrP(1-36) and not hPTH(1-34) is likely to be the actual
      amino-terminal secretory form of PTHrP, and because this previously reported lack
      of potency was unexpected, we repeated these studies using hPTHrP(1-36) and
      compared the results with those obtained with hPTH(1-34). Healthy subjects (n =
      30) were infused over 6 h with either vehicle alone, hPTH(1-34) at a dose of 8
      pmol/kg.h, or hPTHrP(1-36) at doses of 8 or 80 pmol/kg.h. Both hPTH(1-34) and
      hPTHrP(1-36) caused an increase in serum ionized calcium, a decrease in serum
      phosphorus, an increase in the fractional excretion of phosphorus, a decrease in
      the tubular maximum for phosphorus, an increase in nephrogenous cAMP excretion,
      and suppression of endogenous PTH(1-84). Unlike events observed in HHM, hPTHrP(1
      36) induced an increase in plasma 1,25-dihydroxyvitamin D2. In addition,
      fractional excretion of calcium was reduced by both hPTH(1-34) and hPTHrP(1-36).
      In their actions on serum calcium, renal calcium and phosphorus handling, and
      nephrogenous cAMP excretion, hPTHrP(1-36) and hPTH(1-34) appeared equivalent in
      potency. These studies indicate that short-term infusion of hPTHrP(1-36) into
      humans reproduces most but not all of the features of HHM. In contrast to the
      reported findings with hPTHrP(1-34), we found the potency of hPTHrP(1-36) to be
      comparable with that of hPTH(1-34) in vivo in humans. In addition, unlike the
      situation in HHM, hPTHrP(1-36) produces an increment in plasma 1,25
      dihydroxyvitamin D2. Finally, hPTHrP(1-36) has been shown for the first time to
      have anticalciuric effects in humans. This would suggest that, in addition to
      osteoclastic bone resorption, tubular reabsorbtion of calcium by hPTHrP may
      contribute to the hypercalcemia in patients with HHM.

PMID- 8550753
TI  - Glucose homeostasis during spontaneous labor in normal human pregnancy.
AB  - Using stable isotope, glucose turnover was measured in six normal pregnant women
      during the various stages of labor; during the latent (A1) and active (A2) phases
      of cervical dilatation, during fetal expulsion (B), and during placental
      expulsion (C). These data were compared to measurements made in five postpartum
      women. Pancreatic hormones and cortisol were also measured. In four other normal
      women undergoing spontaneous labor, catecholamines and free fatty acids were
      measured. Plasma glucose increased throughout labor from 4.0 +/- 0.2 (A1) to 5.5
      +/- 0.5 mmol/L (C) (P < 0.01), compared to 4.7 +/- 0.1 in the postpartum women.
      Glucose utilization and production were increased throughout labor at 33.4 +/-
      3.1 and 32.8 +/- 3.1 mumol/kg min, respectively, compared to 8.2 +/- 0.9 in
      postpartum women. Glucose metabolic clearance was also increased to 7.5 +/- 0.8
      mL/kg.min compared to that in nonpregnant women (1.8 +/- 0.3). Plasma insulin
      remained at 59 +/- 5 pmol/L during stages A1, A2, and B, but increased to 115 +/-
      15 pmol/L during stage C. Plasma glucagon was increased throughout labor at 127
      +/- 7 pg/mL, compared to 90 +/- 4 pg/mL in control postpartum women. Plasma
      cortisol increased during labor from 921 +/- 136 to 2018 +/- 160 nmol/L, compared
      to 645 +/- 355 during the postpartum period. Epinephrine and norepinephrine also
      increased during labor from 218 +/- 132 pmol/L and 1.09 +/- 0.16 nmol/L to 1119
      +/- 158 and 3.61 +/- 1.04, respectively. It is concluded that labor is associated
      with a marked increase in glucose utilization and production. These findings
      suggest that muscle contraction (uterus and skeletal) independent of insulin is a
      major regulator of glucose utilization during labor. Furthermore, the increase in
      hepatic glucose production could be favored by an increase in glucagon,
      catecholamines, and cortisol.

PMID- 8550754
TI  - More basic isoforms of serum gonadotropins during gonadotropin-releasing hormone
      agonist therapy in pubertal children.
AB  - An acute challenge of exogenous GnRH elicits rapidly increased serum gonadotropin
      levels with qualitative changes to more basic isoforms of both FSH and LH.
      Chronic GnRH agonist therapy suppresses endogenous gonadotropins, and the serum
      levels of FSH and LH are low and fairly constant. A possible qualitative change
      in the gonadotropins during GnRH agonist therapy was investigated by
      determination of the median charge of the gonadotropin isoforms before and during
      therapy in 18 pubertal children. Two different GnRH agonists were studied:
      buserelin, given intranasally or as a sc implant for 1.5-34 months to five girls,
      aged 7-10 yr, and for 5-6 months to two boys, aged 11-13 yr; and triptorelin,
      administered as a depot preparation for 3-6 months to four girls, aged 9-12.5 yr,
      and for 1-24 months to seven boys, aged 10.5-12 yr. FSH and LH in serum and
      eluates after electrophoresis in 0.10% agarose suspension were measured with
      sandwich fluoroimmunoassays. The mean serum FSH and LH levels decreased
      significantly (P < 0.05) in girls during triptorelin therapy, whereas only the
      FSH level decreased (P < 0.05) in the boys. There were no significant (P > 0.05)
      changes in serum gonadotropin levels during buserelin therapy. All of the
      children had more basic serum isoforms of LH, and all but one had more basic
      forms of FSH during the GnRH agonist treatments. In a girl who had more basic
      gonadotropin isoforms after treatment with triptorelin for 2 and 6 months, a GnRH
      challenge elicited the release of still more basic isoforms. The changes in mean
      median charge to more basic gonadotropin isoforms were highly significant for
      both busereline (P < 0.01) and triptorelin (P < 0.001) treatment. An increased (P
      < 0.001) degree of charge heterogeneity was observed for FSH after triptorelin
      therapy. These findings show that there is a qualitative change in the isoforms
      of both FSH and LH in serum during GnRH agonist therapy in pubertal children. The
      changes in charge to more basic gonadotropin isoforms most likely reflect a
      direct effect at the pituitary level, leading to the synthesis and/or selective
      release of less sialylated and sulfated isoforms of the gonadotropins. The
      observed qualitative changes in the gonadotropin isoforms in these pubertal
      children may be part of the clinical effects of GnRH agonist therapy, leading to
      an arrest or regression of puberty.

PMID- 8550755
TI  - Multifactorial control of the elimination kinetics of unbound (free) growth
      hormone (GH) in the human: regulation by age, adiposity, renal function, and
      steady state concentrations of GH in plasma.
AB  - To evaluate the principal determinants of the MCR and plasma t1/2 of unbound
      (free) GH in man, we performed steady state infusions of 3 doses of recombinant
      human GH during pharmacological suppression (iv octreotide) of endogenous GH
      secretion in 24 healthy adults and 12 patients (6 adults and 6 children) with
      chronic renal failure (CRF). Free plasma GH was calculated from total plasma GH
      (measured by immunoradiometric assay) and GH-binding protein activity
      (radioligand assay). The MCR of free GH was determined from free plasma GH and
      the rate of recombinant human GH infusion. The t1/2 of free plasma GH, and the
      concentration and the in vivo dissociation constant (Kd) of GH-binding protein
      (GHBP) were estimated by dynamic modeling of the postinfusion total plasma GH
      concentration decay curves. The MCR of free GH decreased and the plasma GH t1/2
      increased significantly with increasing plasma GH concentrations. The MCR of free
      GH over its physiological concentration range was positively correlated with the
      body mass index as a measure of relative obesity and negatively related to age,
      but only at supraphysiological GH concentrations. In the adult patients with CRF,
      the MCR of free GH was decreased at each infusion rate by 25-38%, and the t1/2
      was increased by 80-170%. Children with CRF showed a significantly lower MCR and
      higher t1/2 of plasma free GH than adult patients. Modeling and direct
      measurements of the off-rate of GH from its high affinity GHBP indicated normal
      dissociation rate constants but decreased molar concentrations of the GHBP in
      uremic plasma. We conclude that the rate of elimination of free GH from plasma in
      man is controlled by 1) plasma total free GH concentrations, 2) relative obesity,
      and 3) renal function within the physiological GH concentration range, whereas 4)
      age is a negative predictor of MCR only at supraphysiological GH concentrations.

PMID- 8550756
TI  - Outcome of severe congenital hypothyroidism: closing the developmental gap with
      early high dose levothyroxine treatment.
AB  - We have previously reported that despite neonatal screening, children with severe
      congenital hypothyroidism treated at 5 weeks of age with 6 micrograms/kg.day
      levothyroxine have clinically significant intellectual impairment, whereas those
      with the moderate form of the disease are indistinguishable from controls. The
      developmental outcome of children with severe congenital hypothyroidism treated
      earlier with higher initial doses of levothyroxine remained to be determined. In
      the present study, 45 infants with permanent congenital hypothyroidism detected
      by neonatal screening are described. For the group, the median age at starting
      treatment was 14 days, and the median initial dose of levothyroxine was 11.6
      micrograms/kg.day. Based on the area of their knee epiphyses at diagnosis, the
      patients were divided into 2 subgroups: severe (< 0.05 cm2; n = 10) and moderate
      (> or = 0.05 cm2; n = 35). The psychomotor development of 8 patients in each
      subgroup, matched for the socioeducational level of their families, was assessed
      at 18 months. Mean plasma free T4 levels were supraphysiological during the first
      few months of life, but mean plasma T3 levels remained within the normal range,
      and there were no signs or symptoms of hyperthyroidism. The mean plasma TSH
      concentration was less than 4.5 mIU/L 4 weeks after starting treatment. Bone
      maturation remained delayed at 12 months in the severe cases and was not unduly
      advanced in the moderate cases. The mean (+/- SD) developmental quotients at 18
      months were similar in severe and moderate cases (107 +/- 10 and 110 +/- 5,
      respectively). We conclude that with earlier treatment and a higher initial dose
      of levothyroxine, the early developmental outcome of infants with severe
      congenital hypothyroidism is now indistinguishable from that of infants with the
      moderate form of the disease who were used as controls.

PMID- 8550757
TI  - Changes in corticosteroid sensitivity of peripheral blood lymphocytes after
      strenuous exercise in humans.
AB  - Although plasma corticosteroid concentrations can be measured accurately, the
      biological effect on the target tissue is uncertain. The availability of an
      accurate measure of corticosteroid sensitivity would potentially clarify the
      putative roles of endogenous glucocorticoids in illnesses such as inflammatory
      disease and obesity and allow evaluation of an additional regulatory level of
      glucocorticoid action. To measure corticosteroid sensitivity, we developed an
      assay based on the inhibition by dexamethasone (Dex) of lipopolysaccharide (LPS)
      induced Interleukin-6 (IL-6) production and release in whole unseparated blood in
      vitro. LPS induced a dose-dependent increase in IL-6 concentrations up to 34 +/-
      6.6 ng/mL, reaching plateau levels after 8 h, whereas Dex dose dependently
      inhibited LPS-induced IL-6 production. Involvement of the glucocorticoid receptor
      in this response was supported by abrogation of Dex (10(-7) mol/L) inhibition of
      IL-6 production by the glucocorticoid receptor antagonist RU 38486. To determine
      whether corticosteroid sensitivity is a dynamic phenomenon, we subjected healthy
      males to a graded quantifiable exercise associated with increases in plasma ACTH
      and cortisol. Before exercise, 3 x 10(-8) mol/L Dex inhibited LPS-induced IL-6
      production in vitro; after exercise, 3 x 10(-8) and 10(-7) mol/L Dex were unable
      to inhibit IL-6 production. We conclude that Dex suppression of LPS-induced IL-6
      production is an effective means of determining corticosteroid sensitivity, and
      that corticosteroid sensitivity in human subjects is a dynamic, rather than a
      static, phenomenon.

PMID- 8550758
TI  - Partial androgen insensitivity caused by an androgen receptor mutation at amino
      acid 907 (Gly-->Arg) that results in decreased ligand binding affinity and
      reduced androgen receptor messenger ribonucleic acid levels.
AB  - Androgen insensitivity is an X-linked disorder of sexual differentiation
      resulting from mutations in the androgen receptor (AR) gene. In this paper, we
      report the clinical phenotype and molecular analysis of two siblings with severe
      partial androgen insensitivity due to a novel mutation in the ligand-binding
      domain of the AR gene. Binding studies using cultured genital skin fibroblasts
      demonstrated reduced AR affinity and binding capacity. Nucleotide sequence
      analysis of the AR gene of both siblings revealed a point mutation causing a
      glycine to arginine amino acid substitution at position 907 within a conserved
      region of the ligand-binding domain. A silent guanine to adenine substitution was
      also identified in the protein-coding region of exon 1. Using an expression
      vector in which the identified mutation was recreated by site-directed
      mutagenesis, the mutant receptor was found to have a reduced binding affinity (Kd
      = 3.06 nmol/L) for mibolerone compared with that of normal AR (Kd = 1.71 nmol/L)
      when expressed in COS-7 cells. In cotransfection experiments using CV-1 cells and
      a mouse mammary tumor virus-chloramphenicol acetyltransferase reporter system,
      the concentration of dihydrotestosterone required to induce half-maximal
      chloramphenicol acetyltransferase gene expression was 50-fold higher in cells
      transfected with the mutant AR complementary DNA than in cells transfected with
      normal AR complementary DNA. AR messenger ribonucleic acid levels in genital skin
      fibroblasts determined by both competitive PCR amplification and ribonuclease
      protection assay were decreased compared with normal values. Our studies
      demonstrate the importance of this region of the AR gene in normal AR function
      and AR gene expression.

PMID- 8550759
TI  - Uptake and metabolism of 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine by
      human liver-derived cells: HepG2 cells as a model for thyroid hormone handling by
      human liver.
AB  - The uptake and metabolism of T3 and rT3 was studied in human liver-derived HepG2
      cells. The results showed a saturable, time-dependent, and ouabain-sensitive
      increase in nuclear bound T3. The effects of ouabain (0.5 mmol/L) and unlabeled
      T3 (10 nmol/L and 10 mumol/L) were much more pronounced at the nuclear level,
      suggesting the presence of a nonspecific component in total cellular binding.
      Nuclear binding of rT3 remained below the detection limit in all experiments.
      Comparison of rT3 metabolism in HepG2 cells and primary cultures of rat
      hepatocytes showed an approximately 10-fold lower iodide production in HepG2
      cells. Iodide production was decreased in the presence of ouabain and almost
      absent in the presence of propylthiouracil (100 mumol/L). Our data confirmed the
      presence of a carrier-mediated uptake system for both T3 and rT3. Metabolism data
      indicated functional type I deiodinase activity in HepG2 cells, the presence of
      glucuronidating enzymes, and the absence of thyroid hormone sulfotransferase
      activity. Based on these data, we propose that HepG2 cells provide an appropriate
      model for thyroid hormone handling by human liver. In addition, we suggest that
      in human liver sulfation of thyroid hormone, and therefore deiodination of T3 is
      of only minor importance.

PMID- 8550760
TI  - The use of recombinant human thyrotropin produced by Chinese hamster ovary cells
      for the preparation of immunoassay reagents.
AB  - Recombinant human TSH (rec-hTSH; Thyrogen, lot M-17073) obtained from transformed
      Chinese hamster ovary cells was tested for both radioiodination and preparation
      of a secondary standard used in RIA and immunoradiometric assay (IRMA) for
      routine clinical investigation. Results were compared to those obtained with high
      quality pituitary TSH (pit-hTSH; Dr. P. Torjesen, Oslo, Norway; and NIDDK,
      Rockville, MD), traditionally used in these assays. After extensive
      characterization and testing, it was found that [125I]rec-hTSH matched all
      binding and chromatographic criteria usually obtained with [125I]pit-hTSH,
      including Stokes' radius, labeling, and storage stability, and did not introduce
      any significant bias when used in the measurement of unknown serum samples. A
      preparation of rec-hTSH was calibrated against a local secondary standard as well
      as against two well known international reference preparations (NIDDK hTSH RP-1
      and WHO International Reference Preparation 80/558) by IRMA and RIA. In the RIA,
      NIDDK anti-hTSH-3 polyclonal antibody was used, whereas in the IRMA, two
      commercial preparations were used: a monoclonal antibody as the detecting
      antibody, and a polyclonal antibody as the capture antibody. In both assays, the
      recombinant standard preparation yielded good fit displacement curves, showing
      significant parallelism compared to pit-hTSH and therefore allowing an unbiased
      measurement of unknown serum samples. The specific activity of the rec-hTSH
      preparation calibrated against the WHO International Reference Preparation was
      7.7 IU/mg protein when measured by IRMA and 7.1 IU/mg when measured by RIA. In
      conclusion, these results indicate for the first time that rec-hTSH can fully
      replace pit-hTSH as both standard and tracer in diagnostic in vitro systems such
      as RIA and IRMA, suggesting that other recombinant glycosylated hormones might
      also serve for immunoassay reagent preparation.

PMID- 8550761
TI  - Human ovarian tumor cells: a potential model for thecal cell steroidogenesis.
AB  - Ovarian thecal cell production of C19 steroids (i.e. dehydroepiandrosterone,
      androstenedione, and testosterone) is necessary to provide substrate for
      granulosa cell biosynthesis of estrogen; however, excessive production of C19
      steroids can lead to disorders associated with androgen excess. Because of
      difficulties in obtaining adequate numbers of thecal cells, the biomolecular
      regulation of C19 steroid production and expression of steroidogenic enzymes is
      not well defined. We have overcome this obstacle by developing a highly
      dependable and unique human ovarian thecal-like tumor (HOTT) cell culture model
      system from an ovarian tumor found to produce excessive amounts of C19 steroids.
      Aliquots of freshly dispersed tumor cells were frozen for future use. Once placed
      in monolayer culture, HOTT cells proliferated and could be maintained for
      extended periods. Acutely, cultured HOTT cells increased progesterone and cAMP
      production in response to 2 h of forskolin treatment. These cells were, however,
      unresponsive to treatment with LH. Steroid hormone production continued in cells
      that were maintained in culture for up to 2 months. Analysis of the steroids
      produced by HOTT cells was accomplished using RIA and high performance liquid
      chromatography. Under basal conditions, HOTT cells produced mainly 17 alpha
      hydroxyprogesterone and progesterone. Treatment with forskolin or dibutyryl cAMP
      (dbcAMP) increased the production of progesterone and 17 alpha
      hydroxyprogesterone as well as C19 steroids. Treatment of monolayer cultures of
      HOTT cells with forskolin (0.01 to 20 mumol/L) or dbcAMP (0.01 to 1 mmol/L) for
      48 h increased the production of androstenedione (8- to 15-fold) and progesterone
      (2- to 5-fold). In HOTT cells chronically treated with forskolin or dbcAMP (up to
      72 h), progesterone production was observed to plateau, although the amount of
      androstenedione continued to increase. The enzymatic activities of both 3 beta
      hydroxysteroid dehydrogenase (6-fold), and 17 alpha-hydroxylase P450 (P450c17; 9
      fold) were also increased by activation of the protein kinase A messenger
      pathway. Treatment of HOTT cells with forskolin caused a time-dependent induction
      of the messenger RNAs for cholesterol side-chain cleavage P450, 3 beta
      hydroxysteroid dehydrogenase, and P450c17. No changes in steroidogenic enzyme
      expression were observed following treatment with LH. In conclusion, these data
      demonstrate that certain ovarian tumor cells may serve well as appropriate models
      to study the molecular mechanisms regulating human ovarian thecal cell C19
      steroidogenesis and the expression of steroid-metabolizing enzymes.

PMID- 8550762
TI  - Mutation R96W in cytochrome P450c17 gene causes combined 17 alpha-hydroxylase/17
      20-lyase deficiency in two French Canadian patients.
AB  - Congenital adrenal hyperplasia (CAH) is the most frequent cause of adrenal
      insufficiency and ambiguous genitalia in newborn children. In contrast to CAH
      caused by 21 alpha-hydroxylase and 11 beta-hydroxylase deficiencies, which
      impairs steroid formation in the adrenal exclusively, 17 alpha-hydroxylase/17,20
      lyase deficiency impairs steroid biosynthesis in the adrenals and gonads. The
      sequence of CYP17 gene was determined by direct sequencing of asymmetric PCR
      products in two French-Canadian 46,XY pseudohermaphrodite siblings suffering from
      combined 17 alpha-hydroxylase/17,20-lyase deficiency. The two patients are
      homozygous for the novel missense mutation R96W caused by a C to T transition
      converting codon Arg96 (CGG) into a Trp (TGG) in exon 1. The both parents are
      heterozygous for this missense mutation. We assessed the effect of the R96W
      mutation on 17 alpha-hydroxylase/17,20-lyase activity by analysis of mutant
      enzyme, generated by site-directed mutagenesis, expressed in COS-1 cells. The
      presence of R96W substitution almost completely abolished the activity of the
      mutant protein. The present findings provide a molecular explanation for the
      signs and symptoms of combined 17 alpha-hydroxylase/17,20-lyase deficiency in
      these two patients and provide useful information on the structure-activity
      relationships of the P450c17, enzyme.

PMID- 8550763
TI  - Calcium deficiency in fluoride-treated osteoporotic patients despite calcium
      supplementation.
AB  - To test the hypothesis that the osteogenic response to fluoride can increase the
      skeletal requirement for calcium, resulting in a general state of calcium
      deficiency and secondary hyperparathyroidism, we assessed calcium deficiency,
      spinal bone density, by quantitative computed tomography, and serum PTH in three
      groups of osteoporotic subjects. Two of the three groups had been treated with
      fluoride and calcium (at least 1500 mg/day) for 32 +/- 19 months. Group 1
      consisted of 16 fluoride-treated subjects who had shown rapid increases in spinal
      bone density (+ 3.8 +/- 2.6 mg/cm2 month), group II consisted of 10 fluoride
      treated subjects who had shown decreases or only slow increases in spinal bone
      density (-0.05 +/- 0.6 mg/cm3 month), and group III consisted of 10 age-matched
      untreated osteoporotic controls. Calcium deficiency was assessed by measurement
      of calcium retention after calcium infusion. The results of our studies showed
      that 1) 94% of the subjects in Group I were calcium deficient compared with only
      30% in groups II and III (P < 0.01 for each); 2) the subjects in group I retained
      more calcium (79%) than the subjects in group II (60%, P < 0.001) or the subjects
      in group III (64%, P < 0.005); 3) calcium retention was proportional to serum PTH
      (r = 0.37, n = 36, P < 0.03); and 4) calcium retention was proportional to the
      (previous) fluoride-dependent increase in quantitative computed tomography spinal
      bone density (in groups I and II, r = 0.48, n = 26, P < 0.02). To test the
      hypothesis that the calcium deficiency and the secondary hyperparathyroidism that
      were associated with the positive response to fluoride would respond to
      concomitant calcitriol treatment, a subgroup of 7 calcium-deficient subjects were
      selected from group I and treated with calcitriol (plus fluoride and calcium) for
      an average of 7 months. The calcitriol therapy reduced the calcium deficit in all
      7 subjects, decreasing calcium retention from 80% to 62% (P < 0.02), and
      decreasing PTH from 50 to 28 pg/mL (P < 0.02). Together, these data indicate that
      fluoride-treated osteoporotic subjects may develop calcium deficiency in
      proportion to the effect of fluoride to increase bone formation, and this calcium
      deficit is responsive to calcitriol therapy.

PMID- 8550764
TI  - Insulin-like growth factor (IGF) I and II, IGF-binding proteins, and IGF-binding
      protein proteases are produced by theca and stroma of normal and polycystic human
      ovaries.
AB  - There is increasing evidence for an important regulatory role for the insulin
      like growth factor (IGF) system in the human ovary. IGF-I and -II and IGF-binding
      proteins (IGFBPs)-1 to -4 have been identified by analysis of follicular fluid
      and granulosa cell-conditioned medium and by in situ hybridization and Northern
      and dot blot analyses of ovarian tissues. It has been suggested that
      abnormalities of intraovarian IGF-I or IGFBPs may play a part in the pathogenesis
      of polycystic ovary syndrome. The aim of this study was to identify production of
      IGF-I and -II and IGFBP-1 to -4 by unstimulated normal and polycystic ovaries.
      IGF-I and -II were measured by RIA after acid-gel exclusion chromatography in
      medium conditioned by incubation for 48 h with granulosa cells or explants of
      theca or stroma. Both IGF-I and -II were present in the low nanograms per mL
      range in theca- and stroma-conditioned medium (T+SCM). IGFBPs in T+SCM were
      initially analyzed by Western ligand blotting, which revealed that low mol wt
      IGFBPs were predominant, especially IGFBP-2 (35 kDa). There was a band
      corresponding to 26 kDa with smaller amounts of a 31-kDa band, but only a trace
      of IGFBP-3 (44 and 40 kDa, confirmed by immunoblot). We found no consistent
      differences between normal and polycystic ovary syndrome ovaries, and although
      there was a trend toward increased IGFBP accumulation in response to LH, this was
      not consistent. We were unable to detect IGFs or IGFBPs by Western ligand
      blotting in granulosa cell-conditioned medium. In further studies we attempted to
      measure IGFBP-3 by RIA using two different antisera (alpha-BP-3gl and 1287-2-14)
      that detect different epitopes of IGFBP-3 and allow the presence of proteolytic
      activity to be demonstrated. Results obtained using alpha-BP-3gl were lower than
      those using 1287-2-14, suggesting proteolysis of IGFBP-3 in the medium. There was
      no evidence of proteolysis of serum IGFBP-3 after incubation with conditioned
      medium, but in contrast, radiolabeled [125I]IGFBP-3 was cleaved after incubation
      with T+SCM. Immunoblotting revealed intact IGFBP-2 (35 kDa) and bands of various
      sizes between 16-33 kDa. Immunoreactive fragments of IGFBP-3 between 13-40 kDa
      were seen. In conclusion, T+SCM contained IGF-I and -II. IGFBP-2 and -4 were the
      predominant species of IGFBP in T+SCM. T+SCM also contained significant protease
      activity directed toward IGFBP-2 and -3. Proteolytic activity may be an important
      mechanism by which bioactive IGFs are made available to these tissues.

PMID- 8550765
TI  - The potential for serious consequences from misinterpreting normal responses to
      the rapid adrenocorticotropin test.
AB  - Despite unequivocal published evidence that patients with subnormal hypothalamic
      pituitary-adrenal (HPA) function may respond normally to ACTH, such normal
      results are still considered reliable indications of unimpaired HPA function.
      This view was tested in four patients with clinical features suggesting
      corticotropin deficiency, in whom cosyntropin (0.25 mg, i.v.) raised serum
      cortisol above 560 nmol/L (20 micrograms/dL) at 1 h. All four patients had
      subnormal responses to metyrapone and excellent persistent improvement during
      subsequent glucocorticoid therapy. Serum cortisol concentrations 1 h after
      cosyntropin treatment in these patients closely resembled cortisol concentrations
      1 h after uncomplicated cholecystectomy in six other patients. However, the rapid
      ACTH test in the patients with hypopituitarism failed to indicate whether more
      prolonged stimulation by ACTH or their endogenous stress would stimulate the
      normal continuing rise in serum cortisol, which reached 1358 +/- 170 nmol/L (+/-
      SE) 5 h after the incision in the cholecystectomized patients. As the three
      hypocorticotropic patients who were recognizably stressed had unstressed serum
      cortisol levels despite persistent adrenocortical reserve (shown by their ACTH
      responses) and recovered during glucocorticoid therapy, the ACTH test, if
      interpreted to indicate normal HPA function, would probably have had disastrous
      consequences. We conclude that a normal response to the rapid ACTH test can be
      dangerously misleading, particularly in incomplete ACTH deficiency states.

PMID- 8550766
TI  - A new compound heterozygous frameshift mutation in the type II 3 beta
      hydroxysteroid dehydrogenase (3 beta-HSD) gene causes salt-wasting 3 beta-HSD
      deficiency congenital adrenal hyperplasia.
AB  - We report a new compound heterozygous frameshift mutation in the type II 3 beta
      hydroxysteroid dehydrogenase (3 beta-HSD) gene in a Pakistanian female child with
      the salt-wasting form of 3 beta-HSD deficiency congenital adrenal hyperplasia.
      The child, born with clitoral enlargement, manifesting salt-wasting adrenal
      crisis, and public hair growth during infancy, was treated with hormonal
      replacement therapy. The etiology of her congenital adrenal hyperplasia, however,
      was not defined. Two of her siblings, as well as one paternal cousin with
      ambiguous genitalia and palpable gonads and another paternal cousin with normal
      female genitalia, had symptoms of adrenal crisis and died during early infancy.
      Thus, although the family history suggested possible 3 beta-HSD deficiency
      disorder, suppressed adrenal function caused by excess glucocorticoid therapy in
      this child at 7 yr of age did not allow hormonal diagnosis. To confirm 3 beta-HSD
      deficiency, we sequenced the type II 3 beta-HSD gene in the patient, her family,
      and the parents of her decreased paternal cousins. The type II 3 beta-HSD gene
      region of a putative promoter, exons I, II, III, and IV, and exon-intron
      boundaries were amplified by PCR and sequenced in all subjects. The DNA sequence
      of the child revealed a single nucleotide deletion at codon 318 [ACA (Thr)-->AA]
      in exon IV in one allele, and two nucleotide deletions at codon 273 [AAA(Lys)-
      >A] in exon IV in the other allele. The remaining gene sequences were normal. The
      codon 318 mutation was found in one allele from the father, brother, and parents
      of the deceased paternal cousins. The codon 273 mutation was found in one allele
      of the mother and a sister. These findings confirmed inherited 3 beta-HSD
      deficiency in the child caused by the compound heterozygous type II 3 beta-HSD
      gene mutation. Both codon 273 and 318 mutations yielding frameshift and premature
      stop codons at codons 279 and 367, respectively, are predicted to result in an
      altered and truncated type II 3 beta-HSD protein, thereby causing salt-wasting 3
      beta-HSD deficiency in the patient. The type II 3 beta-HSD gene findings and
      clinical history of her family members suggest that the patient's deceased
      siblings were likely affected males with the same compound heterozygous mutations
      of the gene as in the proband, whereas the deceased cousins were likely affected
      with the homozygous codon 318 mutation in the gene.

PMID- 8550767
TI  - Long-term effects on testicular function of high-dose testosterone treatment for
      excessively tall stature.
AB  - High-dose testosterone treatment is applied during puberty to reduce the
      predicted adult height in excessively tall boys. To date it has remained unclear
      whether this therapy produces any long-term effects on reproductive functions of
      the patients. To clarify this question, we performed a follow-up study in 47 tall
      men, determining seminal and hormonal parameters 10.6 +/- 2.5 years (mean +/- SD)
      after cessation of therapy. The tall men treated were compared with 123 normal
      men attending the Institute of Reproductive Medicine as volunteers for various
      clinical studies. Clinical examination revealed a significantly higher prevalence
      of varicoceles and history of maldescended testes in the testosterone-treated
      tall men compared with the controls. Semen analysis revealed significantly lower
      progressive motility in the tall men compared with the normal men (49.2 +/- 13.4
      vs. 54.3 +/- 12.8%). A nonsignificant tendency towards lower sperm concentration
      (43.8 +/- 35.4 vs. 57.8 +/- 45.6 mL/mL), lower total sperm count (184.4 +/- 158.0
      vs. 225.4 +/- 277.5 mL/ejaculate), and reduced normal sperm morphology (27.6 +/-
      12.5 vs. 30.9 +/- 13.1%) was evident in the testosterone-treated tall men.
      Although there was no difference in testicular volume and FSH between the groups,
      testosterone was lower in the testosterone-treated tall men (19.9 +/- 7.4 vs.
      23.9 +/- 7.0 nmol/L). Statistical analysis of the subgroups of testosterone
      treated tall men and control men without varicocele and cryptorchidism revealed
      no differences in any ejaculate parameter. The small difference in semen
      variables may be explained by a higher prevalence of varicocele and maldescended
      testes in the testosterone-treated tall men.

PMID- 8550768
TI  - Modulation by insulin of follicle-stimulating hormone and luteinizing hormone
      actions in human granulosa cells of normal and polycystic ovaries.
AB  - Anovulation in polycystic ovary syndrome (PCOS) is associated with
      hyperinsulinemia and insulin resistance, but it has been unclear whether the
      ovary is insulin resistant in women with PCOS. The aims of this study were,
      firstly, to determine whether human granulosa cells respond to physiological
      concentrations of insulin and, secondly, to investigate insulin and gonadotropin
      interactions in vitro in granulosa cells obtained from normal (N) and polycystic
      ovaries (PCO). Granulosa cells were incubated with insulin with or without
      gonadotropins for 48 h. Insulin augmented not only basal production of estradiol
      and progesterone, but also LH-stimulated steroid accumulation in granulosa cell
      cultures from N and PCO. Insulin enhanced FSH-stimulated progesterone production
      by granulosa cells from N and PCO, but the effect on FSH-stimulated estradiol
      production was variable, ranging from no effect for granulosa cells from N to
      synergistic for granulosa cells from PCO of anovulatory subjects. Preincubation
      with insulin for 48 h increased subsequent basal and LH-induced, but not FSH
      stimulated, steroid production. These data demonstrate that granulosa cells from
      PCO respond to insulin despite the association, in vivo, of PCOS with peripheral
      insulin resistance. Insulin preincubation enhances the subsequent response of
      human granulosa cells to LH. We propose that in anovulatory women with PCOS,
      elevated levels of insulin interacting with LH may contribute to the mechanism of
      anovulation.

PMID- 8550769
TI  - Growth hormone (GH) secretory dynamics in a case of acromegalic gigantism
      associated with hyperprolactinemia: nonpulsatile secretion of GH may induce
      elevated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 levels.
AB  - We describe a case of pituitary gigantism with low levels of growth hormone (GH),
      elevated insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 (IGF-BP
      3). The patient had characteristic clinical features of gigantism and acromegaly.
      The basal serum GH levels ranged from 1.2-1.9 micrograms/L, which were considered
      to be within normal limits. Serum GH response to either insulin-induced
      hypoglycemia or GH-releasing hormone was blunted. Frequent blood samplings during
      daytime and at night showed nonpulsatile GH secretion. Serum prolactin, IGF-I and
      IGF-binding protein-3 levels were elevated. After unsuccessful surgery,
      bromocryptine treatment normalized serum prolactin without affecting serum GH and
      IGF-I levels. Combined administration of octreotide and bromocryptine reduced
      serum GH and IGF-I levels. GH bioactivity as measured by Nb2 cell proliferation
      assay was within reference range. In the present case, nonpulsatile GH secretion
      and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-I and IGF
      BP-3 and cause clinical acromegalic gigantism.

PMID- 8550770
TI  - Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis.
AB  - Although a growing body of evidence supports that alkali therapy in diabetic
      ketoacidosis (DKA) might be counterproductive, our knowledge about the
      consequences of this treatment on ketone metabolism is limited. Consequently, we
      performed clinical and animal studies to further examine this topic. The clinical
      studies assessed seven patients with DKA treated with continuous insulin infusion
      at a low dosage. Three of them also received sodium bicarbonate (NaHCO3), whereas
      the remaining four acted as controls. The group receiving NaHCO3 showed a 6-h
      delay in the improvement of ketosis as compared with controls. In addition, there
      was an increase in acetoacetate (AcAc) levels during alkali administration,
      followed by an increase in 3-hydroxybutyrate (3-OHB) level after its completion.
      Significant differences were not found between groups in the response of plasma
      glucose to the overall therapy. The animal study examined the effects of a NaHCO3
      rich perfusate on the hepatic production of ketones with the in situ rat-liver
      preparation. Alkali loading resulted in an immediate increase in the AcAc level
      followed by increases in both the 3-OHB level and the 3-OHB/AcAc ratio after its
      completion. Hepatic ketogenesis increased even further, to about twice the basal
      level, after termination of the NaHCO3 loading. This investigation confirms that
      alkali administration augments ketone production and unravels an effect of
      bicarbonate infusion that promotes a selective build up of AcAc in body fluids.
      The data support that alkali therapy in DKA has nonsaltuary effects in the
      metabolism and plasma levels of ketones.

PMID- 8550771
TI  - Differential effects of short-term fasting on pulsatile thyrotropin,
      gonadotropin, and alpha-subunit secretion in healthy men--a clinical research
      center study.
AB  - In healthy subjects, short term fasting suppresses the hypothalamic-pituitary
      thyroid and hypothalamic-pituitary-gonadal (HPG) axes, with decreased serum
      levels of TSH and LH. However, effects of fasting on pulsatile release of TSH,
      LH, FSH, and alpha-subunit are less clear. Eleven healthy young men each
      underwent two 2-day studies: a baseline study during normal caloric intake and a
      fasting study during 56 h of caloric deprivation. During the final 24 h of each
      study, blood samples were drawn every 15 min for measurement of serum TSH, LH,
      FSH, and alpha-subunit pulses. Fifty-six hours of fasting caused a 50%
      suppression of mean TSH levels and TSH pulse amplitude, without altering TSH
      pulse frequency. Nocturnal TSH pulse amplitude decreased by 60%, with abolition
      of the usual nocturnal TSH surge. Fasting suppressed mean LH levels and LH pulse
      amplitude by 30%, without affecting LH pulse frequency. In contrast, mean FSH
      levels only decreased by 13%, without changes in FSH pulse parameters, whereas
      mean alpha-subunit levels and pulse amplitude decreased by 20%. These data show
      that short term fasting has a greater suppressive effect on the hypothalamic
      pituitary-thyroid axis than on the HPG axis. Within the HPG axis, FSH is more
      resistant to fasting-induced suppression than LH, implying discordant regulation
      of the two gonadotropins during nutritional deprivation. alpha-Subunit
      suppression during fasting appears to parallel that seen for LH.

PMID- 8550772
TI  - Gene conversion in the CYP11B2 gene encoding P450c11AS is associated with, but
      does not cause, the syndrome of corticosterone methyloxidase II deficiency.
AB  - Cytochrome P450c11AS (aldosterone synthase) has 11 beta-hydroxylase, 18
      hydroxylase, and 18-oxidase activities and is expressed solely in the adrenal
      zona glomerulosa. Corticosterone methyloxidase II (CMOII) deficiency denotes a
      rare disorder of adrenal steroidogenesis in which only the 18-oxidase activity of
      P450c11AS is disrupted, while the 11 beta-hydroxylase and 18-hydroxylase
      activities persist. Such patients have elevated serum concentrations of
      corticosterone and 18-hydroxycorticosterone and very low or unmeasurable
      concentrations of aldosterone, often resulting in a clinical salt-losing crisis
      in infancy. One pair of point mutations, Arg181-->Trp and Val386-->Ala, has been
      previously characterized to cause this disorder in an inbred Iranian Jewish
      population. We have sought mutations causing CMOII deficiency in outbred
      populations. In three of four unrelated P450c11AS alleles from two unrelated
      patients with CMOII deficiency, we found a gene conversion event in which exons 3
      and 4 of the CYP11B2 gene encoding P450c11AS were changed to the sequence of the
      nearby CYP11B1 gene, which encodes the related enzyme P450c11 beta. This
      conversion resulted in a mutant P450c11AS protein carrying three changes: Asp141-
      >Glu, Lys151-->Asn, and Ile246-->Thr. We built seven vectors expressing P450c11AS
      carrying each mutation singly, each of the three possible pairs of mutations, and
      the triple mutation as found in the proband. The activities of both the normal
      P450c11AS and the various mutants in transfected nonsteroidogenic COS-1 cells
      were very low, but their activities in steroidogenic MA-10 and JEG-3 cells were
      10- to 20-fold higher. In these systems all of the mutants retained normal 18
      oxidase activity, indicating that the detected gene conversion event is
      associated with but does not cause CMOII deficiency. None of the four CYP11B2
      alleles in these two patients bore other identifiable mutations. These patients
      might have mutations in the promoters or other noncoding regions, or mutations in
      genes other than CYP11B2 may cause the syndrome of CMOII deficiency.

PMID- 8550773
TI  - Gastric emptying, glucose responses, and insulin secretion after a liquid test
      meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2
      (noninsulin-dependent) diabetic patients.
AB  - The aim of the study was to investigate whether inhibition of gastric emptying of
      meals plays a role in the mechanism of the blood glucose-lowering action of
      glucagon-like peptide-1-(7-36) amide [GLP-1-(7-36) amide] in type 2 diabetes.
      Eight poorly controlled type 2 diabetic patients (age, 58 +/- 6 yr; body mass
      index, 30.0 +/- 5.2 kg/m2; hemoglobin A1c, 10.5 +/- 1.2%) were studied in the
      fasting state (plasma glucose, 11.1 +/- 1.1 mmol/L). A liquid meal of 400 mL
      containing 8% amino acids and 50 g sucrose (327 Kcal) was administered at time
      zero by a nasogastric tube. Gastric volume was determined by a dye dilution
      technique using phenol red. In randomized order, GLP-1-(7-36) amide (1.2
      pmol/kg.min; Saxon Biochemicals) or placebo (0.9% NaCl with 1% human serum
      albumin) was infused between -30 and 240 min. In the control experiment, gastric
      emptying was completed within 120 min, and plasma glucose, insulin, C-peptide,
      GLP-1-(7-36) amide, and glucagon concentrations transiently increased. With
      exogenous GLP-1-(7-36) amide (plasma level, approximately 70 pmol/L), gastric
      volume remained constant over the period it was measured (120 min; P < 0.0001 vs.
      placebo), and plasma glucose fell to normal fasting values (5.4 +/- 0.7 mmol/L)
      within 3-4 h, whereas insulin was stimulated in most, but not all, patients, and
      glucagon remained at the basal level or was slightly suppressed. In conclusion,
      GLP-1-(7-36) amide inhibits gastric emptying in type 2 diabetic patients.
      Together with the stimulation of insulin and the inhibition of glucagon
      secretion, this effect probably contributes to the blood glucose-lowering action
      of GLP-1-(7-36) amide in type 2-diabetic patients when studied after meal
      ingestion. At the degree observed, inhibition of gastric emptying, however, must
      be overcome by tachyphylaxis, reduction in dose, or pharmacological interventions
      so as not to interfere with the therapeutic use of GLP-1-(7-36) amide in type 2
      diabetic patients.

PMID- 8550774
TI  - Current trends in the management of well differentiated papillary thyroid
      carcinoma.
AB  - Clinical members of the American Thyroid Association were surveyed in regard to
      their diagnostic assessment, treatment, and long term assessment of
      differentiated papillary thyroid carcinoma. For a 39-yr-old female with a 2-cm
      solitary nodule and no history of radiation (index patient), respondents were
      asked to provide their preferences for diagnostic evaluation, treatment assuming
      a papillary carcinoma was focal, and follow-up. Of 408 surveys mailed, 233
      (57.1%) were analyzed. Diagnostic studies included thyroid scan (56%), fine
      needle aspiration (96%), total serum T4 (49%), and third generation TSH (56%).
      Treatment included surgery (99%), with 86% preferring near-total/total
      thyroidectomy. After surgery, 61% recommended 131I ablation; long term therapy
      using L-T4 alone was recommended by 97%, with most preferring suppression to a
      target TSH level of less than 0.01 microIU/mL (22%), 0.01-0.05 (38%), or 0.06
      0.50 (32%). For variations from the index patient, respondents' treatment were
      not different for a history of radiation, age of either 16 or 60 yr, nodule size
      of 1.5 cm, male sex, the presence of less than 1-cm multiple foci in the
      contralateral lobe, or capsular invasion of the nodule. Treatment and follow-up
      did change if there was blood vessel invasion or distant metastasis. In summary,
      our survey indicated consensus on diagnostic assessment of the index patient by
      fine needle aspiration and management by surgery and 131I therapy. However,
      management varied widely for the ablative dose of 131I, the target TSH level
      after ablation, and the frequency and type of follow up.

PMID- 8550775
TI  - Localization and regulation of corticotropin receptor expression in the
      midgestation human fetal adrenal cortex: implications for in utero homeostasis.
AB  - Developmental changes in the responsiveness of the fetal adrenals to
      corticotropin (ACTH) play an important role in the regulation of the fetal
      hypothalamic-pituitary-adrenal axis. Responsiveness of adrenal cortical cells to
      ACTH is dependent on the extent of ACTH receptor expression. Therefore, we
      examined the localization and regulation of ACTH receptor expression in the
      midgestation (16-24 weeks) human fetal adrenal cortex. In situ hybridization
      analysis was used to localize messenger RNA (mRNA) encoding the ACTH receptor in
      sections of human fetal adrenal glands. Messenger RNA encoding the ACTH receptor
      was localized in cells from all cortical zones; abundance was higher in
      definitive zone than in fetal zone cells and was least abundant in the more
      central portions of the cortex. Regulation of ACTH receptor expression was
      studied using Northern blot analysis of total RNA extracted from primary cultures
      of fetal and definitive zone cells. Two major (1.5 and 3.5 kilobases) and, upon
      stimulation with ACTH, 3 minor (4.0, 6.0 and 10.0 kb) ACTH receptor mRNA
      transcripts were detected in RNA from fetal and definitive zone cells. In both
      cell types, ACTH-(1-24) increased the abundance of mRNA encoding the ACTH
      receptor 10- to 20-fold compared with untreated cells. The effects of ACTH-(1-24)
      on ACTH receptor expression in fetal zone cells were time- and dose-dependent.
      The ED50 for the stimulation of ACTH receptor expression by ACTH-(1-24) was 1-10
      pM, and maximal response to 0.1 nm ACTH-(1-24) was detected after 12-16 h. Eight
      bromoadenosine cAMP and forskolin also stimulated ACTH receptor expression in
      fetal zone cells and closely mimicked the effects of ACTH-(1-24). In contrast,
      stimulation of protein kinase C with 12-O-tetradecanoyl phorbol 13-acetate had no
      effect on ACTH receptor expression. Changes in ACTH receptor expression in
      response to ACTH-(1-24), cAMP and forskolin were paralleled by changes in
      expression of the P450 cholesterol side chain cleavage (P450scc) enzyme. These
      data demonstrate that expression of the ACTH receptor by the human fetal adrenal
      cortex is up-regulated by its own ligand and that this effect is mediated by a
      cAMP-dependent mechanism. In addition, the coordinate stimulation of ACTH
      receptor and P450scc expression by ACTH indicates that the gene for the ACTH
      receptor is one of a specific cohort of genes regulated by ACTH that are required
      to facilitate fetal adrenal cortical response to ACTH. ACTH regulation of its own
      receptor may represent a mechanism by which fetal adrenal responsiveness to ACTH
      is maintained and possibly enhanced during fetal development.

PMID- 8550776
TI  - The accuracy of parathyroid gland localization in primary hyperparathyroidism
      using sestamibi radionuclide imaging.
AB  - Primary hyperparathyroidism is a common condition due to either a parathyroid
      adenoma or, less commonly, parathyroid hyperplasia, whose treatment is
      essentially surgical. We have, therefore, assessed the accuracy of Tc-99m
      pertechnetate/Tc-99m sestamibi (methoxy-isobutyl isonitrile) imaging in the
      localization of adenomas and hyperplastic parathyroids. The clinical records of
      all patients who had Tc-99m pertechnetate/Tc-99m sestamibi imaging and
      parathyroid surgery at this hospital were reviewed. The technique used involves
      standard subtraction methodology with the addition of a novel change detection
      algorithm to optimize localization. Of 46 patients scanned in 48 patient
      episodes, 36 patients had adenomas; 28 (78%) were accurately localized to the
      correct quadrant, and 4 were correctly lateralized. Two patients with parathyroid
      carcinomas had their metastases correctly localized. Thus, in 34 of 38 (89.5%) of
      the scans, adenomas or carcinomas were able to be anatomically localized. Six
      patients presented with hyperplasia; 5 were diagnosed by sestamibi scans, and 3
      of these accurately localized all hyperplastic glands. Four additional patients
      had known hyperplasia, of which 2 were rendered normocalcemic after removal of
      their sestamibi-positive glands; the other 2 had small second glands detected
      only at surgery. In patients with unknown pathology, imaging suggested that 6
      patients had hyperplasia; this was correct in 5 cases (83%). Nine of the 12 scans
      in patients who had had previous parathyroid surgery accurately localized the
      tumors, 7 in the neck and 2 outside. We suggest that sestamibi imaging can help
      to distinguish hyperplasia from adenomatous disease; when imaging is required, we
      recommend it as the imaging modality of choice in all patients with primary
      hyperparathyroidism, especially in reoperated patients.

PMID- 8550777
TI  - Vascular endothelial growth factor localization in human ovary and fallopian
      tubes: possible role in reproductive function and ovarian cyst formation.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also
      increases vascular permeability. We hypothesized that VEGF plays a role in the
      regulation of cyclic ovarian angiogenesis in women, and that its ability to
      increase vascular permeability may be an important factor in the production of
      fallopian tube effluent and fluid formation in ovarian cysts. To examine these
      hypotheses, we assessed VEGF expression in ovaries and fallopian tubes from
      premenopausal (n = 10) and postmenopausal (n = 4) women. Immunohistochemical
      analysis for VEGF was performed using a rabbit polyclonal antibody directed
      against human VEGF. In normal ovaries from premenopausal women, VEGF within
      healthy follicles was localized to the thecal cell layer, with minimal VEGF
      peptide detected in the granulosa cell layer. VEGF was not expressed in atretic
      follicles or a degenerating corpus luteum. However, intense VEGF immunostaining
      was observed within the highly vascularized corpora lutea in all specimens
      examined. In normal ovaries from postmenopausal women, VEGF was detected only in
      epithelial inclusion cysts and a serous cystadenoma. In specimens from both pre-
      and postmenopausal women, the luminal epithelium of the fallopian tube as well as
      smooth muscle cells and pericytes lining small and large blood vessels within the
      tube and hilum of the ovary exhibited specific staining for VEGF. Based on these
      data, we suggest that during reproductive life, VEGF plays a role in the growth
      and maintenance of the ovarian follicle and corpus luteum by mediating
      angiogenesis. In addition, VEGF within the fallopian tube luminal epithelium may
      increase vascular permeability and modulate tubal luminal secretions. Similarly,
      VEGF in the epithelial lining of benign ovarian neoplasms may contribute to fluid
      formation in ovarian cysts.

PMID- 8550778
TI  - Expression and function of thyroid hormone receptor variants in normal and
      chronically diseased human liver.
AB  - As the liver represents a major target organ for thyroid hormone action, we
      compared the expression of thyroid hormone receptor (TR) alpha and beta variants
      in normal human liver and liver affected by primary biliary cirrhosis, sclerosing
      cholangitis, cryptogenic cirrhosis, and alcoholic cirrhosis (n = 6 in each
      group). Western blot analysis using specific polyclonal antibodies to alpha 1 or
      beta 1 TRs or to the related non-T3-binding c-erbA alpha 2 variant revealed
      abundant expression of TRs in normal and diseased liver, with no difference in
      size or abundance of TR proteins. Immunocytochemistry likewise revealed abundant
      nuclear expression of TR proteins in normal and diseased liver, with similar
      patterns and intensity of staining. Despite abundant TR protein expression,
      Northern blot hybridization of polyadenylated ribonucleic acid (RNA; 10
      micrograms) to TR complementary DNAs revealed only a weak signal for c-erbA alpha
      2 messenger RNA (mRNA). Comparison of the level of expression of the thyroid
      hormone-regulated mRNAs encoding T4-binding globulin, sex hormone-binding
      globulin, cortisol-binding globulin, and transthyretin in normal and diseased
      tissue revealed no significant difference, suggesting that hepatocellular
      expression of these mRNAs is maintained in chronic liver disease despite a marked
      reduction in circulating T3 concentrations.

PMID- 8550779
TI  - Evidence for numerous brown adipocytes lacking functional beta 3-adrenoceptors in
      fat pads from nonhuman primates.
AB  - Brown adipose tissue (BAT) is involved in the control of energy balance and has
      been demonstrated to be activated through beta 3-adrenoceptor (beta 3-AR)
      occupation in rodents. The ability to specifically activate energy expenditure
      via this receptor is of great interest for the treatment of obesity.
      Nevertheless, the extent of BAT and the presence of a functional beta 3-AR in
      humans are now debated, and this situation is difficult to clarify for evident
      practical and ethical reasons. We investigated the occurrence of brown adipocytes
      in fat deposits of prepubertal baboons using antibodies raised against uncoupling
      protein (UCP) in Western blotting and immunocytology experiments. UCP was
      detected in all types of fat pads studied and was revealed in multilocular cells.
      Pericardiac and axillary adipose tissues displayed large amounts of UCP and can
      be assimilated to typical BAT. Most of the other pads looked like white adipose
      tissue, but exhibited areas with clusters of brown adipocytes and, thus, can be
      assimilated to the convertible adipose tissue as previously described in rodents.
      The presence of beta 3-ARs was evaluated by both beta 2-agonist-stimulated
      lipolysis and messenger ribonucleic acid (mRNA) expression studies. There was no
      significant lipolytic effect of any of the beta 3-AR agonists tested (SR 58611A,
      BRL 37344, CGP 12177, or CL 316243) in either white or brown tissues. PCR
      analysis demonstrated that beta 3-AR mRNA expression is not related to the UCP
      content of fat pads and that beta 3-AR expression is low. This study demonstrates
      the presence of great proportions of brown adipocytes in adipose tissue and the
      heterogeneity of the fat pads in baboons. The lack of a metabolic effect of beta
      3-agonists combined with the weak expression of beta 3-AR mRNAs raise the
      question of the role of beta 3-ARs in adipose tissues of primates.

PMID- 8550780
TI  - Comparison of the effects of estrogen alone and estrogen plus androgen on
      biochemical markers of bone formation and resorption in postmenopausal women.
AB  - The present study was undertaken to determine whether the addition of an androgen
      to estrogen therapy in postmenopausal women would alter the skeletal response as
      determined by measurements of markers of bone formation and resorption.
      Postmenopausal women were treated for 9 weeks with either a combination of 1.25
      mg esterified estrogen and 2.5 mg methyltestosterone (E+A) or 1.25 mg conjugated
      equine estrogen (CEE). Both groups showed a similar decrease in urinary excretion
      of the bone resorption markers, deoxypyridinoline, pyridinoline, and
      hydroxyproline. Patients treated with CEE showed decreases in the serum markers
      of bone formation, bone-specific alkaline phosphatase, osteocalcin, and C
      terminal procollagen peptide. In contrast, subjects treated with E+A showed
      increases in these markers of bone formation. CEE increased, and E+A decreased
      serum levels of sex hormone-binding globulin as well as triglycerides and high
      density lipoprotein levels. Only CEE significantly reduced low density
      lipoproteins. Both regimens were effective in reducing postmenopausal somatic
      symptoms, but only E+A had a significant effect on psychological symptoms. We
      conclude that short term administration of androgen with estrogen may reverse the
      inhibitory effects of estrogen on bone formation. Long term studies are needed to
      determine the relative benefits and risks of the combination of estrogen and
      androgen and whether this results in greater increases in bone mass and strength.

PMID- 8550781
TI  - Defective organification of iodide causing congenital goitrous hypothyroidism.
AB  - A 26-yr-old Japanese woman with congenital goitrous hypo-thyroidism and
      sensorineural deafness underwent a thyroidectomy. Examination of the thyroid
      gland revealed characteristic features of multinodular goiter. The T3 and T4
      content in thyroglobulin (Tg) were 0.03 and 0.02 mol/mol Tg, respectively. Iodide
      incorporation into Tg, using slices of the thyroid tissue, revealed that iodide
      organification of thyroid tissue from our patient was markedly lower than that of
      normal controls. Then, guaiacol and iodide oxidation activities of thyroid
      peroxidase (TPO) in our patient's thyroid tissue were lower than those of normal
      controls (guaiacol assay: 1.92 vs. 30.0 +/- 5.7 mGU/mg protein; iodide assay: 1.1
      vs. 6.6 +/- 2.8 mIU/mg protein). Lineweaver-Burk plot analysis of the oxidation
      rates of guaiacol and iodide indicated that this patient's TPO had a defect in
      the binding of guaiacol and iodide, but the coupling activity of the patient's
      TPO was not decreased compared with those of two normal thyroids. In this case
      and in control subjects, Nothern gel analysis of TPO messenger RNA from
      unstimulated and TSH-stimulated thyroid cells revealed a 3.2 kilobase species in
      the former and four distinct messenger RNA species of 4.0, 3.2, 2.1, and 1.7
      kilobases in the latter. Western blot analysis of TPOs obtained from this patient
      and from control subjects identified the same 107 kDa protein, using
      antimicrosomal antibody-positive serum. We analyzed the coding sequence in the
      patient's TPO gene by using polymerase chain reaction technique. A single point
      mutation of G-->C at 1265 base pair was detected only in the TPO gene, but this
      point mutation does not alter the amino acid residue. It is possible that
      posttranslational modification such as abnormal glycosylation may occur in the
      TPO molecules. Furthermore, it is possible that there are differences in the
      tertiary structures of the TPO molecules between our patient and normal subjects.
      The above abnormalities of TPO molecules may play an important role in our
      patient's dyshormonogenesis.

PMID- 8550782
TI  - Immunohistochemical localization of steroid 5 alpha-reductase 2 in the human male
      fetal reproductive tract and adult prostate.
AB  - The activity of the type 2 isozyme of steroid 5 alpha-reductase is crucial for
      normal development of the external genitalia and prostate in human males. We used
      immunohistochemistry to localize type 2 isozyme expression in the human male
      fetal reproductive tract and adult prostate. In fetal tissue, the stroma of the
      seminal vesicles, corpus cavernosum, corpus spongiosum, dorsal vein complex,
      scrotal skin, and prostate expressed the enzyme. In addition, the epithelial
      cells of the fetal urethra and proximal prostatic ducts stained positively. The
      type 2 isozyme could not be detected in epithelial cells of the fetal prostatic
      acini, seminal vesicles, prostatic utricle, ejaculatory ducts, epididymides, and
      Cowper's glands. Adult prostate specimens were derived from transurethral
      prostatectomies performed for benign prostatic hyperplasia. Enzyme expression in
      these benign prostatic hyperplasia samples localized to the stroma and epithelial
      cells of the urethra and proximal ducts. No staining was detected in the acinar
      (luminal and basal) epithelial cells. Double staining with an antismooth muscle
      actin antibody localized type 2 isozyme expression to the stromal fibroblast
      cells of the prostate. Double staining with an androgen receptor antibody
      localized AR expression to the acinar epithelial cells and stromal fibroblasts.
      These data indicate that 5 alpha-reductase type 2 is expressed throughout the
      developing male genitourinary tract and functions as both an autocrine and a
      paracrine mediator of growth and differentiation.

PMID- 8550783
TI  - Expression of prohormone convertase, PC2, in adrenocorticotropin-producing thymic
      carcinoid with elevated plasma corticotropin-releasing hormone.
AB  - An autopsy case of ACTH-producing thymic carcinoid with Cushing's syndrome is
      reported. The patient was a 63-yr-old man with multiple bone metastases from an
      undetermined primary site. Hyperpigmentation was observed at the terminal stage.
      The plasma levels of ACTH, cortisol, chromogranin A, and urinary 17-hydroxy
      corticosteroids were extremely high, and ectopic ACTH-producing neuroendocrine
      tumor was diagnosed. In addition, plasma CRH was high. Autopsy revealed that the
      patient had primary thymic carcinoid with extensive metastases. Remarkable
      hyperplasia of the adrenal cortexes and Crooke's hyaline degeneration of the
      pituitary gland were consistent with Cushing's syndrome by ectopic ACTH
      production. There were multiple CRH-producing cells without degenerative changes
      in the hypothalamus. The tumor cells were immunoreactive to ACTH, CRH, and the
      cleavage enzyme PC2. POMC messenger ribonucleic acid and PC2 messenger
      ribonucleic acid were detected in the tumor cells by an in situ hybridization
      method. Expression of PC2 was considered to induce hyperpigmentation by producing
      alpha MSH. Despite hypercortisolism and ectopic production of CRH by the tumor
      cells, hypothalamic CRH cells were not atrophic. This case is a good example to
      demonstrate the correlation between CRH and the hypothalamo-pituitary-adrenal
      axis as well as hyperpigmentation in Cushing's syndrome.

PMID- 8550784
TI  - The human prolactin receptor in the fetal membranes, decidua, and placenta.
AB  - Human PRL is synthesized and secreted by the maternal decidua, but not by the
      chorionic cytotrophoblast of the chorion laeve or the placenta. The sites of
      action for decidual PRL are currently unknown. Accordingly, Northern analysis and
      in situ hybridization histochemistry have been used respectively to quantitate
      and localize the expression of the PRL receptor (PRL-R) gene within the uterus
      during the peripartal period. Immunocytochemistry and Western blot analysis using
      an anti-PRL-R antibody (U5) localized the translated protein at the cellular
      level in the same tissues. As judged by the level of expression of the PRL-R gene
      and its translated products, the chorionic cytotrophoblast has been shown to be a
      primary site of action. Novel sites were also shown in the decidua, placental
      trophoblast, and amniotic epithelium. In situ hybridization was not obtained in
      the latter despite positive Northern analysis and immunostaining. Western
      analyses with an antibody (U5) to the extracellular domain of the rat PRL-R
      detected six major molecular species of 95, 85, 63, less than 63, more than 30,
      and 30 kDa in cytosol from separated amnion, chorion, and decidua. The two bands
      at 95 and 85 kDa were approximate values only and represent the mature
      glycosylated forms of the human PRL-R. The other four major bands were partial
      degradation products from the PRL-R, showing tissue-specific processing and
      patient to patient variation related to the spectrum of proteases present in
      these tissues. The 63- and 30-kDa PRL-R-related proteins were detected in both
      the cytosol and medium from amnion, chorion, and decidua and were also present in
      amniotic fluid. The 30-kDa species was equal in size to a recently reported PRL
      binding protein in human milk. The release of these two PRL-R-related proteins
      into amniotic fluid suggests possible functions as binding and or/PRL transport
      proteins in these tissues. The more than 30-kDa species was detected in high
      amounts in both cytosol and medium from the decidua, but was absent from amniotic
      fluid. Further work is required to clarify the structural relationships and
      potential functions of these immunologically PRL-R-related proteins. This study
      shows that the PRL-R is widely expressed by both fetal and maternal tissues in
      late pregnancy. Its increased expression during labor and delivery in the
      chorion, decidua, and placenta supports an autocrine/paracrine role for decidual
      PRL in the peripartum.

PMID- 8550785
TI  - Metastatic papillary thyroid carcinoma to lung diagnosed by bronchoalveolar
      lavage.
AB  - The diagnosis of papillary carcinoma of the thyroid metastatic to the lung
      frequently requires a battery of noninvasive tests. Occasionally, invasive
      procedures such as open lung biopsy, transthoracic needle biopsy, and
      transbronchial lung biopsy are employed to confirm the diagnosis. A 31-yr-old
      woman with papillary thyroid carcinoma treated previously by a near-total
      thyroidectomy and 131I ablation presented to our clinic with shortness of breath
      and a clear chest roentgenogram. A post-131I treatment whole body scan revealed
      widespread 131I pulmonary uptake, and the presence of papillary thyroid cancer
      was confirmed by bronchoalveolar lavage. We conclude that bronchoalveolar lavage
      should be considered when tissue confirmation of metastatic papillary carcinoma
      to the lung is needed. During the evaluation and follow-up of this patient, we
      were able to determine that metastatic papillary carcinoma to the lung may cause
      a methacholine bronchoprovocation test to be falsely positive for asthma.

PMID- 8550786
TI  - Insulin-like growth factor-binding protein-2 and -3 expression in benign human
      prostate epithelium, prostate intraepithelial neoplasia, and adenocarcinoma of
      the prostate.
AB  - Insulin-like growth factor (IGF)-binding proteins (IGFBPs) modulate the activity
      of IGFs. In vitro human prostate epithelial cells secrete IGFBP-2 and -3. In vivo
      IGFBP-2 is increased, and IGFBP-3 is decreased in the serum of patients with
      prostate cancer. Immunohistochemistry and in situ hybridization were performed to
      compare the expression of IGFBP-2 and -3 in vivo in prostate tissue containing
      benign epithelium, high grade prostate intraepithelial neoplasia (PIN), and
      adenocarcinoma. Immunoreactivity and messenger ribonucleic acid (mRNA)
      hybridization signals for IGFBP-2 and -3 were localized to epithelial cells.
      IGFBP-2 immunostaining intensity was significantly increased in PIN regions
      compared to that in normal epithelium and was further increased in malignant
      cells. IGFBP-2 mRNA was also significantly increased in PIN and cancer cells.
      IGFBP-3 immunoreactivity was significantly increased in PIN regions compared to
      normal epithelium; however, IGFBP-3 protein was significantly decreased in
      malignant cells. IGFBP-3 mRNA remained virtually unchanged in benign epithelium,
      PIN, and adenocarcinoma cells. These results demonstrate that increased IGFBP-2
      protein in PIN and malignant cells is probably due to increased mRNA expression.
      However, levels of IGFBP-3 protein may be due to pre- and/or posttranslational
      mechanisms, including proteolysis. The changes in IGFBP-2 and -3 protein levels
      in prostatic tissue are in agreement with serum changes reported in patients with
      prostate cancer.

PMID- 8550787
TI  - Lack of effect of recombinant human growth hormone (GH) on muscle morphology and
      GH-insulin-like growth factor expression in resistance-trained elderly men.
AB  - Vastus lateralis muscle samples were obtained by needle biopsy from 18 healthy
      elderly men (65-82 yr) participating in a double blind, placebo (PL)-controlled
      trial of recombinant human GH (rhGH) and exercise and assessed for muscle
      morphology and skeletal muscle tissue expression of GH and insulin-like growth
      factors (IGFs). Subjects initially underwent progressive resistance training for
      14 weeks and were then randomized to receive either rhGH (0.02 mg/kg BW.day, sc)
      or PL while undertaking a further 10 weeks of training. Muscle samples were
      obtained at baseline and at 14 and 24 weeks. The mean (+/- SEM) cross-sectional
      areas of type I and II fibers were similar (type I, 3891 +/- 167 microns2; type
      II, 3985 +/- 200 microns2) at baseline and increased (P < 0.01) by 16.2 +/- 4.1%
      and 11.8 +/- 3.8%, respectively, after the initial 14-week training period. After
      treatment (weeks 14-24), two-way repeated measures ANOVA revealed a main effect
      of time for type I (P < 0.01) and type II fibers (P < 0.05), but no group effect
      or interaction. The increase in cross-sectional area for the PL group was
      significant (P = 0.01) for type I (11.5 +/- 3.6%) and approached significance (P
      = 0.06) for type II fibers (11.1 +/- 5.6%). For rhGH, the change in type I (6.3
      +/- 5.9%) and II (7.1 +/- 5.2%) fiber area was not significant. No apparent
      change in tissue GH receptor, IGF-I, IGF-I receptor, IGF-II, or IGF-II receptor
      messenger ribonucleic acids occurred as a result of exercise after the 14-week
      pretreatment period or after treatment with rhGH or PL. These results indicate
      that rhGH administration in exercising elderly men does not augment muscle fiber
      hypertrophy or tissue GH-IGF expression and suggests that deficits in the GH-IGF
      I axis with aging do not inhibit the skeletal muscle tissue response to training.

PMID- 8550788
TI  - Reduced preovulatory granulosa cell steroidogenesis in women with endometriosis.
AB  - To examine the cause of altered follicular fluid steroid levels and lower in
      vitro fertilization rate observed in infertile women with minor endometriosis, we
      have compared the production of estradiol (aromatase activity) and progesterone
      of freshly isolated granulosa cells (3h. incubation) from such women and a
      control group with tubal or unexplained infertility, having IVF during
      unstimulated or gonadotropin-stimulated cycles. As previously observed, mature
      oocytes from women with endometriosis had a reduced fertilization and cleavage
      rate in vitro in unstimulated cycles (19/37[51%] vs. 69/94[73%], p < 0.05) and
      stimulated cycles (20/37[57%] vs. 32/39[82%], p < 0.01). Median [95%CI] basal
      aromatase activity was lower in endometriosis compared with control in
      unstimulated cycles (2.84[2.03-3.49] pmol E2/10(3) cells/3h, n = 31 vs. 3.63[2.72
      3.49], n = 55, p = 0.057) and stimulated cycles (0.31[0.16-0.50], n = 14 vs.
      0.99[0.70-1.52], n = 20, p < 0.001). Progesterone production followed a similar
      pattern in unstimulated (0.56[0.50-0.89] pmol/10(3) cells/3h, n = 29 vs.
      1.23[0.69-1.54], n = 52,) and stimulated (0.37[0.20-0.73], n = 16 vs. 0.95[0.72
      1.17], n = 21) cycles (p < 0.05). Addition of FSH, LH or hCG (30ng/mL) to the
      incubation medium enhanced progesterone production 2 to 3-fold, but had no effect
      on aromatase activity. Our results indicate a defect in granulosa cell
      steroidogenesis associated with endometriosis, which could affect oocyte function
      and explain the reduction in fertilizing capacity and subsequent competence of
      the corpus luteum, and the associated subfertility.

PMID- 8550789
TI  - RET mutation screening in sporadic pheochromocytoma.

PMID- 8550790
TI  - Ectopic nonfunctioning pituitary adenoma in the sphenoid sinus.

PMID- 8550791
TI  - Effects of estrogen therapy on whole body proteins.

PMID- 8550792
TI  - Effects of growth hormone and insulin-like growth factor I in men with idiopathic
      osteoporosis.
AB  - Injections with growth hormone (GH) or insulin-like growth factor I (IGF-I) have
      been proposed for anabolic therapy in osteoporosis. In a cross-over study, 12 men
      with idiopathic osteoporosis received daily subcutaneous injections of GH (2
      IU/m2) or IGF-I (80 micrograms/kg) for 7 days with 12 weeks of wash-out. Serum
      levels of procollagen type I increased by 29% following treatment with GH (P <
      0.001) and by 43% with IGF-I (P < 0.001 compared with pretreatment levels; P <
      0.05 compared with GH injections), whereas both treatments rendered a 20%
      increase in osteocalcin concentrations (P < 0.001), indicating enhanced bone
      formation. There was also evidence of stimulated bone resorption, as the urinary
      levels of deoxypyridinoline increased by 44% following GH injections (P < 0.001)
      and by 29% following IGF-I (P < 0.001), and there were 28% higher serum
      concentrations of IGF-I after GH than after IGF-I injections. Although markers of
      bone metabolism increased under both treatments, comparison of the treatments
      suggests that IGF-I enhanced formation of collagen type I more than did GH.
      Furthermore, the stimulation of bone resorption was detected as soon as 4 days
      after the initiation of GH injections. Some of the differences might be dose
      dependent, but could also indicate separate mechanisms at the cellular level.

PMID- 8550793
TI  - Angiotensin II receptor characteristics and subtype expression in uterine
      arteries and myometrium during pregnancy.
AB  - The uteroplacental vasculature is less sensitive to angiotensin II (ANG II)
      induced vasoconstriction than the systemic vasculature. Although the mechanism(s)
      responsible is unclear, uterine arteries (Ua) may demonstrate ANG II receptor (AT
      receptors) down-regulation or expression of AT2 receptors, which do not mediate
      vasoconstriction. We determined AT receptor binding characteristics and subtype
      expression in Ua from normotensive pregnant (n = 14; 38 +/- 0.5 weeks gestation)
      and nonpregnant (n = 28) women. Comparative studies were performed with
      myometrium, a nonvascular smooth muscle. We measured binding density (Bmax) and
      affinity (Kd) in plasma membrane preparations employing radioligand binding.
      Receptor subtypes were assessed by inhibiting [125I]ANG II binding with specific
      antagonists. During pregnancy, the Ua Bmax and Kd were unchanged (P > 0.1; 221 +/
      36 vs. 159 +/- 27 fmol/mg protein and 0.8 +/- 0.1 vs. 0.9 +/- 0.1 nmol/L,
      respectively). However, myometrial Bmax decreased 92% (580 +/- 129 vs. 44 +/- 7
      fmol/mg protein; P < 0.001), and Kd rose 4-fold (1.5 +/- 0.4 to 6.0 +/- 0.6
      nmol/L; P < 0.001). AT1/AT2 expression averaged 15%/85% in Ua from nonpregnant
      and pregnant women, whereas in myometrium, values were 10%/90% and 60%/40%,
      respectively. In myometrium from laboring women (n = 8), force (1.38 +/- 0.14 to
      1.59 +/- 0.12 x 10(4) N/m2; P < 0.04) and contractile frequency (0.038 +/- 0.05
      to 0.116 +/- 0.014 contractions/min; P < 0.001) increased with 10(-5) mol/L ANG
      II and were abolished by AT1 receptor inhibition. Myometrium from nonpregnant
      women (n = 3) was unresponsive, and AT2 inhibition did not alter responses. In
      nonpregnant women, AT2 receptors predominate in Ua and myometrium. Although Ua AT
      receptors are unaltered during pregnancy, myometrial Bmax decreases, reflecting
      decreases in the expression of AT2 >> AT1 receptors and differential receptor
      regulation.

PMID- 8550794
TI  - Dehydroepiandrosterone, dehydroepiandrosterone sulfate, obesity, waist-hip ratio,
      and noninsulin-dependent diabetes in postmenopausal women: the Rancho Bernardo
      Study.
AB  - Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) levels
      were determined in morning specimens from 659 fasting postmenopausal women who
      were not using estrogen therapy or antidiabetic medication. All women had
      concurrent oral glucose tolerance tests and measurements of body mass index (BMI)
      and waist-hip ratio (WHR). DHEA levels were weakly and inversely associated with
      BMI but not with WHR or glucose tolerance status. DHEAS levels were not
      associated with BMI but were positively associated with WHR, diabetes, and
      impaired glucose tolerance. In analyses adjusted for or stratified by WHR, the
      DHEAS association with abnormal carbohydrate tolerance was reduced but still
      independent of fat distribution. Because this was a cross-sectional study, it was
      not possible to determine whether DHEAS levels were raised by central obesity or
      vice versa. At a minimum, these data strongly suggest that the positive
      association of DHEAS with both central obesity and abnormal glucose tolerance
      does not support the thesis that DHEAS protect against diabetes or obesity in
      older women as had been suggested by animal studies.

PMID- 8550795
TI  - Thyroid cancer and the Chernobyl accident.

PMID- 8550796
TI  - Androgens regulate circulating levels of insulin-like growth factor (IGF)-I and
      IGF binding protein-3 during puberty in male baboons.
AB  - To examine the role of androgens in initiating the pubertal rise in circulating
      insulin-like factor-I (IGF-I) levels, a longitudinal study of puberty in 13 male
      hamadryas baboons was conducted over 3 yr. The five control baboons commenced
      puberty (initial testicular enlargement) at a mean +/- SE age of 4.2 +/- 0.4 yr.
      Another eight baboons were castrated prepubertally; of those four received
      testosterone pellets (dose equivalent: 12.5-50 mg every 6 weeks) implanted se
      from the time of puberty. Body weight, crown-rump length, and limb length
      measurements, synchronized to pubertal onset, suggest that a pubertal growth
      spurt occurs in male baboons. Control baboons had a marked rise (4- to 5-fold; P
      < 0.0001) in circulating IGF-I levels; maximum IGF-I levels (168 +/- 9 nmol/L)
      were reached 42 months after the onset of puberty (mean chronological age 7.5
      yr). Castrated baboons had no significant rise in IGF-I levels, however,
      administration of testosterone resulted in a close approximation of the normal
      pubertal rise in IGF-I (maximum values 140 +/- 8 nmol/L), confirmed by comparison
      of fitted sigmoid curves (r2 > 0.99; chronological age ED50 controls, 4.4 +/- 0.1
      yr and castrate + testosterone, 4.3 +/- 0.1 yr). Serum IGF binding protein-3
      levels paralleled the rise in IGF-I consistent with a common regulatory
      mechanism. In another study, castration of four sexually mature male baboons aged
      11.12 +/- 1.16 yr had no effect on serum IGF-I levels (P = 0.5). This indicates
      that androgens are the predominant determinant of circulating IGF-I in the male
      baboon, and that this is an uniquely pubertal phenomenon.

PMID- 8550797
TI  - Inhibition of lipopolysaccharide-induced monocyte interleukin-1 receptor
      antagonist synthesis by cortisol: involvement of the mineralocorticoid receptor.
AB  - Glucocorticoids, as a part of their physiological role in the control of
      inflammatory and immune processes, suppress the expression of interleukin-1 (IL
      1) and other cytokines. Human monocyte IL-1 receptor antagonist (IL-1ra)
      messenger ribonucleic acid (mRNA) expression and protein secretion are inhibited
      by dexamethasone. We have now further studied the regulation of IL-1ra by the
      major physiological human glucocorticoid, cortisol. We found that cortisol
      incubation induced a decrease in IL-1ra mRNA expression and a significant
      inhibition of IL-1ra protein secretion in cell cultures of human peripheral
      monocytes stimulated with the bacterial endotoxin lipopolysaccharide (LPS). Oral
      administration of 276 mumol cortisol to normal subjects also decreased LPS
      induced IL-1ra synthesis in cultured monocytes. By coincubating the monocytes
      with either the mineralocorticoid antagonist spironolactone or the glucocorticoid
      receptor antagonist RU 38486, the in vitro cortisol-induced inhibition of LPS
      stimulated IL-1ra secretion was partially reversed. The mineralocorticoid
      aldosterone exerted a significant decrease in LPS-induced monocyte IL-1ra
      secretion in vitro, which was blocked by coincubation with spironolactone. In
      addition, the expression of mineralocorticoid receptor mRNA in human monocytes
      was observed by PCR of reversed transcribed RNA. Our results further indicate
      that corticosteroids physiologically control the IL-1/IL-1ra system during
      inflammatory or immune processes. Moreover, we provide evidence that, in addition
      to a glucocorticoid receptor-mediated effect, the mineralocorticoid receptor is
      involved in the inhibition of monocyte IL-1ra secretion by cortisol.

PMID- 8550798
TI  - Gonadotropin-releasing hormone messenger RNA expression in gonadotroph tumors and
      normal human pituitary.
AB  - Gonadotroph tumors predominantly secrete FSH or free gonadotropin hormone
      subunits and rarely LH. In contrast to normal gonadotrophs, a subset of tumors
      synthesize FSH beta-subunit (SU) in excess of alpha-SU, and the cause of
      gonadotropin hormone-SU biosynthetic defects in these tumors is unknown.
      Gonadotropin-releasing hormone (GnRH) is known to modify gonadotropin hormone-SU
      biosynthesis and secretion and may be an important determinant of gonadotroph
      tumor hormone regulation. Data in experimental animals have demonstrated that
      endogenous expression of GnRH may occur in the pituitary. We therefore determined
      whether 1) the GnRH gene is expressed in gonadotroph tumors and normal
      pituitaries using reverse transcriptase (RT)-PCR; 2) the GnRH receptor gene is co
      expressed in gonadotroph tumors; 3) an alternative upstream transcriptional start
      site on the GnRH gene is utilized; and 4) media from primary cultures of
      gonadotroph tumors have detectable GnRH immunoreactivity by RIA. GnRH messenger
      RNA (mRNA) was detected in 10/10 gonadotroph tumors, eight of which expressed
      GnRH-Receptor mRNA. Both mRNAs were detected in all normal pituitaries studied (n
      = 6). Six of 10 gonadotroph tumors and 3/6 normal pituitaries had GnRH
      transcripts derived from the upstream transcriptional start site (5'GnRH). GnRH
      immunoreactivity was detected in overnight media from 3/3 primary gonadotroph
      tumor cultures (range: 1.89-5.86pg/mL; limit of detection (LD) = < 1.58pg/mL) but
      was not detectable in control media. This is the first study to demonstrate
      endogenous GnRH gene expression in human pituitary adenomas and normal human
      pituitary tissue. The presence of both GnRH and GnRH-Rc suggest that GnRH may be
      a paracrine/autocrine regulator of cell function in the pituitary and may affect
      gonadotroph tumor hormone phenotype.

PMID- 8550799
TI  - Assessment of growth hormone (GH) secretion in men with adult-onset GH deficiency
      compared with that in normal men--a clinical research center study.
AB  - It is not known how patients who acquire GH deficiency (GHD) in adulthood differ
      in measures of GH secretion from normal adults. To characterize measures of GH
      secretion in such patients compared to those in normal subjects, we studied 23
      men (median age, 51 yr; range, 32-62 yr) with adult-onset pituitary disease,
      defined as GH-deficient based on having no detectable GH response to two
      pharmacological agents, and 17 normal men. Patients less than 50 yr old received
      insulin (0.1 U/kg, i.v.) and clonidine (0.15 mg, orally), whereas those 50 yr of
      age or older as well as normal controls received arginine (30 g, i.v.) and
      clonidine. Patients were compared to normal men by investigating GH sampling
      every 10 min for 24 h and serum levels of insulin-like growth factor I (IGF-I),
      IGF-binding protein 2 (IGFBP-2), IGFBP-3, and GH-binding protein. Frequent venous
      sampling of GH was analyzed in terms of mean 24-h levels, pooled 24-h GH, mean
      levels over the 12 h between 2000-0800 h (mean overnight GH level), and pulse
      analysis (pulses per 24 h and pulse amplitude) by the Pulsar computer program.
      Although there were significant differences between the two groups for almost all
      measures of GH secretion, overlap between the groups was always present. GH
      levels measured using a highly sensitive chemiluminescence assay on 24-h pools
      derived from frequent sampling displayed the least overlap between the two
      groups, as only 2 of 17 normal controls overlapped with the GHD patients. The
      pooled 24-h GH level using this technique was significantly lower in patients
      with GHD than in controls (0.117 +/- 0.021 vs. 0.861 +/- 0.098 micrograms/L; P <
      0.0001). In the analysis of frequent GH sampling using a standard
      immunoradiometric assay, mean overnight GH levels provided the best separation
      between the two groups, as all 23 patients had values of 0.6 microgram/L or less,
      and 13 of 17 normal controls had values greater than 0.6 microgram/L. The mean
      overnight GH level in patients was 0.6 +/- 0.0 microgram/L compared to 1.0 +/-
      0.1 microgram/L in controls (P < 0.0001). The mean 24-h GH level in patients was
      0.5 +/- 0.0 microgram/L compared to 0.8 +/- 0.1 microgram/L in normal controls (P
      < 0.0001). GH pulse frequency and pulse amplitude were also reduced in patients
      with GHD compared to those in normal controls [1.7 +/- 0.5 vs. 5.1 +/- 0.5
      pulses/24 h (P < 0.0001) and 0.6 +/- 0.1 vs. 2.8 +/- 0.4 microgram/L (P <
      0.0001), respectively]. The mean serum IGF-I level was significantly lower in
      patients with GHD than in normal controls (106.7 +/- 8.0 vs. 218.7 +/- 16.7
      microgram/L; P < 0.0001). Three of 23 patients overlapped with control values.
      Mean serum levels of IGFBP-3 and the serum IGF-I/IGFBP-2 ratio were also
      significantly lower in patients than in controls, but values overlapped
      substantially. We conclude that overlap occurs on measures of GH secretion
      between normal men and men identified as GH deficient despite a stringent
      definition of GHD. The best separation was obtained using pooled 24-h GH levels
      determined by a highly sensitive chemiluminescence assay.

PMID- 8550800
TI  - Thyroid lesions in children and adolescents after the Chernobyl disaster:
      implications for the study of radiation tumorigenesis.
AB  - Eight years after the Chernobyl nuclear accident, the most obvious effect is
      manifested by an increase in the prevalence of thyroid gland diseases in the
      exposed children and adolescents. In this study, we describe a comparative
      analysis of epidemiological, clinical, and morphological features of 92 malignant
      and 59 benign thyroid lesions from patients 5-18 yr of age exposed to radiation
      in Belarus as a result of the Chernobyl disaster. All of them were operated at
      the same institution during the period from September 1991 through December 1992.
      The highest number of patients that subsequently developed thyroid carcinomas was
      in the group that was less that 1 yr of age at the time of Chernobyl, and this
      number decreased progressively through age 12 yr. Conversely, none of the
      patients with benign lesions only was less than 2 yr old at the time of the
      accident, and an exposure age of 5-6 yr was a threshold separating significant
      prevalence of malignant tumors in younger children from the more frequent benign
      lesions in older patients (P < 0.001). Fifty-two percent of children with
      carcinomas and only 24% with benign lesions (P < 0.005) were residents of the
      Gomel region, which is the most contaminated in Belarus. The morphology of
      thyroid tissue adjacent to carcinomas showed a high prevalence of multinodular
      and diffuse changes, but not of adenomas or solitary adenomatoid nodules. There
      was a high prevalence of focal micropapillary hyperplasia with graded degrees of
      severity, which we hypothesize may correspond to precursors for papillary thyroid
      carcinoma in post-Chernobyl radiation-associated tumors.

PMID- 8550801
TI  - 1 alpha, 25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531)
      modulation of insulin-like growth factor-binding protein-3 and induction of
      differentiation and growth arrest in a human osteosarcoma cell line.
AB  - 1 alpha,25-Dihydroxycholecalciferol [1,25-(OH)2D3] is a potent differentiating
      agent in a variety of tumor cell lines. However, the induction of severe
      hypercalcemia has limited its clinical use. Several analogs have been synthesized
      that retain the antiproliferative differentiating effects of 1,25-(OH)2D3, but do
      not have the calcitropic effect of the parent compound. One such analog, 1
      alpha,25(OH)2-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531), can
      induce differentiation in HL-60 cells and does not induce hypercalcemia in animal
      models. We, therefore, evaluated the effect of Ro24-5531 on a human osteosarcoma
      cell line, MG-63. Compared with 1,25-(OH)2D3, the analog Ro24-5531 is 10-100
      times more potent as an inhibitor of MG-63 cell proliferation, as determined by
      [3H]thymidine incorporation and/or 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. The inhibition in cell growth is accompanied
      by a decrease in the expression of p34cdc2 (> 4-fold), a protein critically
      involved in cell cycle regulation. Ro24-5531 treatment of MG-63, at a
      concentration of 10(-8) mol/L, induced expression of the bone differentiation
      markers biglycan and osteocalcin, as determined by Northern analysis. These data
      suggest that Ro24-5531 treatment induces growth arrest coupled with
      differentiation. To begin to evaluate the mechanisms by which Ro24-5531 may exert
      an effect, we evaluated the effect of Ro24-5531 on components of the insulin-like
      growth factor I (IGF-I) signaling pathway, an important regulator of normal bone
      growth and differentiation. The expression of IGF-binding protein (IGFBP), IGFBP
      3 messenger ribonucleic acid, and protein levels are increased 20-fold after 72 h
      of treatment with Ro24-5531 and are associated with a marked increase in
      detectable binding of ligand to binding protein, as measured by RRA. These data
      suggest an association between Ro24-5531-induced growth arrest and increased
      expression of IGFBP-3.

PMID- 8550802
TI  - [Reconstructive surgery using the flaps pedicled by rectus abdominis muscle or
      deep inferior epigastric artery].

PMID- 8550803
TI  - [Long-term results in valve replacement with Bjork-Shiley prosthesis. Analysis of
      life expectancy by relative survival rate].
AB  - Using the U.S. STS guidelines, I analyzed the results of 389 patients who
      underwent Bjork-Shiley valve (BS valve) replacement at Nippon Medical School over
      the past 15 years. In addition, I calculated their relative survival rates using
      the Japanese Abridged Life Table and objectively determined the treatment effects
      by taking into account the patients' postoperative life expectancy. There were
      201 male and 188 female patients, whose mean age at the time of surgery was 52 +/
      12 years. Of these, 151 patients underwent aortic valve replacement (AVR); 185
      had mitral valve replacement (MVR); and 53, aortic and mitral valve replacement
      (DVR). Convexo-Concave models (CC models) were used in 94 patients, and Monosrut
      models (MS models) in 295. Their cumulative follow-up was 2006 patient-years and
      their average observation period was 5.2 +/- 3.6 years (complete follow-up in 98%
      of cases). A total of 32 patients suffered an early death, while 36 suffered a
      late death. At 10 years after surgery, the actual survival rates were 80.3% for
      patients who underwent AVR; 81.9% for MVR; and 70.7% for DVR, indicating no
      significant differences among the three groups (NS). Meanwhile, the relative
      survival rates at 10 years after surgery were 88.6% for patients who underwent
      AVR; 88.2% for MVR; and 75.4% for DVR, indicating that AVR was superior to DVR (p
      < 0.001), with MVR rated between the two. No significant differences were seen
      among the three groups with respect to the occurrence rate of valve-related
      complications. The most frequent complications' thromboembolism occurred at a
      rate of 2.29%/patient-years overall. Strut fractures occurred in two patients
      using the CC models (0.25%/patient-years), but there were no strut fractures
      among those using the MS models. While the effect of atrial fibrillation on the
      subjects' life prognoses was unclear (NS), patients often developed complications
      related to artificial valves (p < 0.025), and their life prognoses were inferior
      to those of patients with sinus rhythm. Survivors reported marked improvements in
      their quality of life, and their late survival rates were satisfactory. However,
      their life expectancy was inferior to that of the normal population.

PMID- 8550804
TI  - [Analysis of duodenal bile acids in patients with colorectal tumors and control
      subjects].
AB  - Bile acids are believed to play a role in the etiology of colorectal cancer. To
      investigate a possible relationship between bile acids and colorectal tumors,
      duodenal bile acids were analyzed in 18 patients with colorectal adenomas, 18
      patients with colorectal carcinoma and 18 control subjects. Using high
      performance liquid chromatography and immobilized 3 alpha-hydroxysteroid
      dehydrogenase in column form, significant increases in the proportion of
      chenodeoxycholic acid and significant decreases in the proportion of deoxycholic
      acid and lithocholic acid were found in the bile of patients with colorectal
      adenoma or carcinoma compared with the control subjects. The data support the
      concept that bile acids have a role to play in the development of large bowel
      tumors.

PMID- 8550805
TI  - [The influence of methionine and its metabolites on the progression of
      atherosclerosis in rabbits].
AB  - The effects of a high level of methionine on the changes of lipid and amino acid
      metabolism were investigated. Eighteen New Zealand White rabbits were divided
      into three groups; a methionine group, which was fed a diet supplemented with 3%
      D, L-methionine, a Cholesterol+Methionine group, which was fed a 3% D, L
      methionine and a 0.2% cholesterol diet, and a Cholesterol group which was fed a
      0.2% cholesterol diet for 22 weeks. The plasma triglyceride, cholesterol,
      homocysteine, cysteine and serum SO4(2-) levels were measured and compared. On
      the first and the final day of the experiment, lipid peroxide levels in blood
      samples were also measured. We found that the Methionine group and the
      Cholesterol+Methionine group showed elevated levels of plasma triglyceride,
      cholesterol, homocysteine, cysteine, serum SO4(2-) and lipid peroxide compared
      with the Cholesterol group. More prominent fat deposits in the aorta were
      observed in the Methionine group and the Cholesterol+Methionine group than in the
      Cholesterol group. Our results indicated that the interaction of cholesterol with
      methionine or its derivatives plays a role in the progression of atherosclerosis.

PMID- 8550806
TI  - [Regional cerebral blood flow in status epileptics measured by single photon
      emission computed tomography (SPECT)].
AB  - Status epileptics (SE) due to a cerebral vascular accident can cause a change for
      the worse in the quality of life of patients. We have performed single photon
      emission computed tomography (SPECT) with 99mTc-hexamethylpropylene amineoxim (HM
      PAO) to evaluate regional cerebral blood flow (rCBF) in SE caused by a cerebral
      vascular accident. In addition, we have discussed the neurophysiology of SE based
      on the SPECT findings. A total of sixteen patients (5 males and 11 females,
      average age; 78.2 years old) with SE who were suffering from prolonged
      consciousness disturbance were investigated. When SPECT was performed in the
      ictal state, there was a remarkable increase in Radio Isotope (RI) uptake at the
      focus which correlated well with EEG findings. However, in other cortical
      regions, basal ganglia and thalamus, there was a relatively demonstrated decrease
      in RI uptake compared with that of the focus. Additionally in the interictal
      state, we found a decrease in RI uptake in the epileptic foci and normal recovery
      of the RI uptake level in other cerebral regions. We speculate that these
      characteristic patterns of cerebral blood flow distribution shown by SPECT scans
      in the ictal state reflect the state of consciousness disturbance due to SE. In
      general, in the elderly, it is difficult to make a differential diagnosis between
      prolonged consciousness disturbance due to nonconvulsive SE and other diseases
      such as cardiovascular, dehydration, metabolic disorder, etc. Nevertheless,
      nonconvulsive SE causes diffuse cell loss and irreversible brain damage.
      Therefore the elderly who have suffered from prolonged consciousness disturbance
      due to SE need an exact diagnosis and immediate medical treatment. When we
      diagnose a nonconvulsive SE, the characteristic findings of SPECT scans in the
      ictal state are very clear and useful. In conclusion, SPECT is a very simple and
      non-invasive method that demonstrates abnormalities of brain function exactly.
      Therefore, we should perform not only EEG but also SPECT scans when making a
      diagnosis of SE.

PMID- 8550807
TI  - The kinetics of ACTH expression in rat leukocyte subpopulations.
AB  - The pro-opiomelanocortin (POMC) gene encodes a family of peptides originally
      identified in the pituitary gland. An important POMC-derived peptide hormone,
      corticotropin (ACTH), is also produced by leukocytes and modulates in vitro
      immune functions. The present investigation was undertaken to determine the
      kinetics and cellular distribution of ACTH immunoreactivity (ACTH-ir) in vitro in
      rat splenic leukocyte subpopulations. Cells were cultured with Concanavalin A
      (ConA), lipopolysaccharide (LPS), or media alone. ACTH-ir was identified with a
      specific antiserum raised against ACTH 1-24. Double indirect-immunofluorescence
      was done at 0, 21, and 48 h for B, t-helper (Th), and T-cytotoxic (CTL) cells.
      Initial kinetic studies demonstrated peak ACTH-ir in all cell types at 18-21 h
      for both ConA and LPS treatments. A few leukocytes (1-2%) expressed ACTH-ir at 0
      h and these were found to be macrophages (MO). Lymphocyte ACTH-ir is 0% at 0 h
      and rises to 90 +/- 5% and 75 +/- 6% at 21 h with ConA and LPS, respectively.
      This sharply contrasts with 9 +/- 4% of each cell type positive in media alone at
      21 h. The percent immunoreactivity among the three lymphocyte subpopulations did
      not significantly differ at any single treatment at a single time point. However,
      there were significant differences in the intensity levels among the
      subpopulations. At 48 h of ConA or LPS treatment only 10 +/- 4% of B, Th and Tc
      were positive, while none were positive in media alone. Stimulated peritoneal MO
      also increase positivity for ACTH-ir (85 +/- 5%). These results indicate that rat
      splenic B, CTL, and Th lymphocytes can be immunologically stimulated to express
      the peptide hormone ACTH and that basal ACTH expression in macrophages is
      distinct from that in lymphocytes. Thus, lymphocyte-derived ACTH may be a
      paracrine or autocrine regulator of immune function.

PMID- 8550808
TI  - Interleukin-6 mRNA expression by cortical neurons in culture: evidence for
      neuronal sources of interleukin-6 production in the brain.
AB  - In this study, we investigated the capacity of murine cortical neurons to express
      interleukin-6 (IL-6) mRNA and protein in culture. Using in situ hybridization
      techniques, IL-6 mRNA was localized to neuronal cells in these cultures.
      Moreover, IL-6 mRNA expression as measured by in situ and PCR was shown to be
      upregulated by the proinflammatory cytokines interleukin-1 beta (IL-1 beta) and
      tumor necrosis factor-alpha (TNF-alpha). This was consistent with the dose and
      time-dependent increases in IL-6 secreted protein observed from cultures
      stimulated with IL-1 beta and TNF-alpha. Taken together, the data suggest that
      neurons are capable of participating more directly in the CNS cytokine network
      than previously thought and may play an important role in the inflammatory
      response activities in the brain.

PMID- 8550809
TI  - Selective effect of methoxyindoles on the lymphocyte proliferation and melatonin
      binding to activated human lymphoid cells.
AB  - Three pineal methoxyindoles (melatonin (Mel), 5-methoxytryptamine (5-MTA) and 5
      methoxytryptophol (5-MTO)) were studied for their ability to influence the
      proliferative response of human peripheral blood lymphocytes (PBL) and tonsillar
      lymphocytes (TL) following activation with concanavalin A (ConA) in vitro. The
      ConA-stimulated DNA synthesis was affected in a different dose-dependent mode by
      the methoxyindoles tested. Melatonin and 5-MTO inhibited and 5-MTA increased the
      ConA-induced [3H]thymidine incorporation in PBL and TL. The initial screening for
      2-[125I]iodomelatonin binding using a single point assay revealed significantly
      increased specific binding to PBL and TL after 72-h stimulation with ConA as
      compared to the non-activated cell cultures. Coincubation of separate lymphocyte
      cultures with ConA and Mel or 5-MTO resulted in inhibition of the specific 2
      [125I]iodomelatonin binding (85% and 74%, respectively). The specific binding
      determined in the presence of 5-MTA did not differ from control values. Series of
      saturation and competition experiments were performed to examine the binding
      characteristics of ConA-stimulated lymphocytes for 2-[125I]iodomelatonin. The
      radioligand labelled binding sites of high affinity (Kd = 0.14 +/- 0.03 nM) and
      low capacity (Bmax = 6.8 +/- 1.5 fM/mg protein). Competitive studies with a
      variety of indoles determined the following order of relative potency for
      inhibition of 2-[125I]iodomelatonin binding in TL: 2-iodomelatonin > melatonin >
      > 5-methoxytryptophol. 5-Methoxytryptamine did not show displacement potency for
      the labelled ligand. Collectively, our data suggest that pineal hormones might be
      directly involved in the regulation of the T-lymphoproliferative response of
      human lymphoid cells. We show the availability of melatonin receptors, which seem
      to be an intrinsic characteristic of activated human lymphocyte populations.
      While the effects of Mel and 5-MTO can be linked to the binding sites described,
      it is unlikely that serotonin agonists like 5-MTA may act through the same sites
      to influence the mitogen-stimulated lymphocyte proliferation.

PMID- 8550810
TI  - The immune profile of multiple sclerosis: T-lymphocyte effects predominate over
      all other factors in cyclophosphamide-treated patients.
AB  - It is widely believed that multiple sclerosis is a T-cell mediated autoimmune
      disease associated with abnormalities in immunoregulation. This large,
      prospective study evaluated the lymphocyte immunophenotypic profile of 246 MS
      patients, divided clinically into a remitting/relapsing group (n = 176) and a
      progressive group (n = 70), and compared their results to those of 117 healthy
      controls. All patients were found to have significantly elevated percentage and
      absolute numbers of IL2R+CD3+ cells as well as depressed percentages of
      CD45RA+CD4+ cells. However, when the factor of treatment with cyclophosphamide
      (CY) versus no treatment or treatment with other agents was used to group
      patients, dramatic declines in both percentages and absolute numbers of
      CD45RA+CD4+ cells were discovered. These declines were associated specifically
      with CY and and could be explained by this factor independent of the clinical
      state of the patient. The effects were seen in patients undergoing current
      treatment or in those exposed to CY in the near or remote past. These findings
      highlight the confounding effect of specific treatments on the immune profile of
      MS patients groups and suggest that there may be important implications for
      cellular function and clinical outcome in these and other patient groups.

PMID- 8550811
TI  - Tumor necrosis factor alpha-308 alleles in multiple sclerosis and optic neuritis.
AB  - Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, is believed
      to play an important role in multiple sclerosis (MS) pathogenesis. A bi-allelic
      polymorphism in the TNF-alpha promoter region (TNF alpha-308), has been reported
      to influence levels of TNF-alpha production. In the present study, we
      investigated the TNF alpha-308 polymorphism in 93 patients with MS, 17 patients
      with optic neuritis (ON) and 95 healthy individuals using an allele-specific PCR
      technique. Allelic genotype was compared with TNF-alpha mRNA expression levels
      and HLA class II phenotypes. No significant difference regarding the TNF alpha
      308 polymorphism was observed between MS patients and controls. Specifically, the
      less common allele, TNF2, which is associated with higher expression levels of
      TNF-alpha, was somewhat less frequent among MS patients. In fact, analysis of 19
      patients homozygous for the MS associated HLA-DR-DQ haplotype HLA-Dw2 showed that
      this haplotype does not carry the TNF2 allele. In addition, in 47 patients, the
      TNF-alpha alleles did not correlate with expression levels measured as numbers of
      TNF-alpha expressing cells. Thus, we found no evidence for an important role of
      TNF alpha-308 polymorphism for genetic susceptibility to MS.

PMID- 8550812
TI  - T cell antigenic and neuritogenic activity of recombinant human peripheral myelin
      P2 protein.
AB  - The major neuritogenic protein of peripheral nerve myelin is the P2 protein.
      Human P2 is a candidate autoantigen in inflammatory demyelinating diseases of the
      peripheral nervous system. Since human P2 is not readily available, we produced
      full-length recombinant human P2 protein (rhP2) in Escherichia coli. RhP2 was
      recognized by neuritogenic rat T cell lines and induced experimental autoimmune
      neuritis in Lewis rats. Production of rhP2 allowed the generation of human T cell
      lines reactive to the autologous protein. Studies of human T cell autoreactivity
      as well as efforts to use hP2 as a tolerogen will be facilitated by the large
      scale expression of rhP2.

PMID- 8550813
TI  - Interferon regulatory factor-2 physically interacts with NF-kappa B in vitro and
      inhibits NF-kappa B induction of major histocompatibility class I and beta 2
      microglobulin gene expression in transfected human neuroblastoma cells.
AB  - Most neural cells constitutively lack major histocompatibility complex (MHC)
      class I and beta 2-microglobulin gene expression. Cytokines and viruses may,
      however, induce expression of these genes in some neural cells, and this
      correlates with factor binding to the NF-kappa B and interferon stimulated
      response elements of these genes. Here, we demonstrate that NF-kappa B is capable
      of inducing MHC class I and beta 2-microglobulin gene expression when transiently
      co-transfected into CHP-126 neuroblastomas, and that IRF-2 represses this
      induction. Interferon regulatory factor-2 (IRF-2) repression of MHC class I and
      beta 2-microglobulin gene expression in CHP-126 neuroblastomas may demonstrate a
      mechanism by which virus persists in neural cells. We show here that IRF-2
      physically interacts in vitro with NF-kappa B. This interaction may contribute to
      the repression of the expression of these genes. Our demonstration that IRF
      family members, in addition to IRF-2, physically interact in vitro with NF-kappa
      B (p50 and p65), provides a general mechanism by which these transcription
      factors may, in concert, regulate the expression of a variety of genes involved
      in immune responses in the brain.

PMID- 8550814
TI  - Mouse microglial cell lines differing in constitutive and interferon-gamma
      inducible antigen-presenting activities for naive and memory CD4+ and CD8+ T
      cells.
AB  - We developed a panel of non-virus transformed cell lines derived from individual
      microglial precursors residing in the brains of normal mice. These colony
      stimulating factor-1-dependent cell lines are B7-1+ (CD80), Mac-1+, Mac-2+, Mac
      3+, CD45+, MHC class I+, colony stimulating factor-1 receptor+, and they ingest
      antibody-coated particles. However, the cell lines differ in their expression of
      B7-2 (CD86), F4/80, Ly-6C and MHC class II molecules. They also differ in their
      ability to constitutively process and present antigens to naive CD4+ and CD8+ T
      cells, memory CD4+ and CD8+, and in the manner by which interferon gamma
      modulates their antigen-presenting activities. These cell lines should be
      valuable as models for studies on the immunobiology of the microglia.

PMID- 8550815
TI  - Effect of prolonged exposure to morphine on responsiveness of human and
      invertebrate immunocytes to stimulatory molecules.
AB  - This study deals with a novel role of morphine in the modulation of cellular
      responsiveness to immunostimulatory substances that, at first glance, appears to
      be in contrast to the well documented immunoinhibitory short-term effects of
      opiate alkaloids on cells simultaneously exposed to stimulatory molecules.
      Vertebrate and invertebrate immunocytes pre-exposed to morphine (10(-6) M) in
      vitro for at least 24 h prior to the administration of lipopolysaccharide (LPS;
      1.0 micrograms/ml) or other immunoactivating substances have revealed a distinct
      enhancement of their responsiveness to these signals, e.g. monocytes exposed to
      LPS alone resulted in 21% activation, whereas the morphine pretreated level was
      at 40% (P < 0.01). Prolonged pretreatment with morphine of naive human monocytes
      had the same effect on their sensitivity to plasma from patients having undergone
      cardiopulmonary bypass (CPB) operations followed by a diffuse inflammatory
      response. These results suggest that endogenous opiates may participate, in more
      than one way, in re-establishing an organism's readiness to meet a new demand on
      its immune system. Additional support for the concept of a role of endogenous
      opiates in immunomodulation was obtained by the results of in vivo tests with
      experimentally induced stress in Mytilus. Following their stress-induced
      stimulation, these animals' immunocytes could be shown to become exposed for some
      time to a measurable rise in endogenous morphine-like material (9 pmol/ml
      increasing to 59). These immunocytes, like those preincubated with exogenous
      morphine, displayed a heightened sensitivity to stimulation by LPS (control 21.3
      +/- 3.1% activation compared to 47.2 +/- 5.1) when the morphine levels dropped.
      The mechanism of this enhancement of responsiveness to immunostimulation
      following the prolonged exposure of immunocytes to morphine, and its relationship
      with the known short-term immunoinhibitory opiate effects on the immune system,
      remains to be ascertained.

PMID- 8550816
TI  - Effects of short-term dexamethasone treatment during pregnancy on the development
      of the immune system and the hypothalamo-pituitary adrenal axis in the rat.
AB  - The effects of glucocorticoid (GC) treatment on the mature immune and
      neuroendocrine system are known to be reversible. However, prenatal GC exposure
      may have irreversible consequences on the development of the newborn. In this
      study, possible long-lasting effects of short-term prenatal GC treatment were
      examined on the developing thymus, spleen and hypothalamo-pituitary adrenal axis
      (HPA axis). Female rats were given dexamethasone (DEX, 400 micrograms, i.p.) on
      day 17 and 19 of pregnancy and offspring was studied at several time intervals (1
      20 days) after birth, for examination of thymus, spleen, hypothalamus and blood
      plasma. Examination of thymus and spleen revealed that prenatal exposure to DEX
      resulted in decreased T cell numbers in thymus and spleen on day 1 after birth.
      Thymus regeneration after DEX exposure both during pregnancy and in adult life
      was completed after 24 days. However, the kinetics of regeneration of the thymi
      after prenatal DEX exposure were different from that seen after DEX in adult
      life. Whereas DEX treatment during pregnancy resulted in an increased ratio of
      CD4+/CD8- thymocytes over CD4-/CD8+ thymocytes compared to control groups on day
      7 and day 20 after birth (time X treatment interaction; P < 0.05), DEX treatment
      in adult life did not change this ratio. T cell numbers in the spleen were
      significantly decreased at all neonatal ages studied. Regarding the hypothalamus,
      prenatal exposure to DEX altered the pattern of neonatal changes in peptide
      expression in corticotropin-releasing hormone neurons, with a selective reduction
      in CRH storage in the median eminence (7 and 9 days after birth) and an increase
      in AVP storage (9 and 20 days after birth). The ratio of AVP over CRH was
      significantly increased at all developmental ages studied. No effects were seen
      on basal ACTH and corticosterone levels in plasma. In conclusion, the kinetics of
      thymus regeneration after DEX exposure during pregnancy were different from that
      seen after DEX exposure in adult life. Prenatal DEX exposure also seemed to delay
      the migration of T cells into the spleen. Furthermore, prenatal DEX treatment
      exerted major effects on hypothalamic CRH neurons that maintained for at least 20
      days after birth, which points towards an enhanced stress responsiveness of the
      HPA axis in later life.

PMID- 8550817
TI  - Protracted, relapsing and demyelinating experimental autoimmune encephalomyelitis
      in DA rats immunized with syngeneic spinal cord and incomplete Freund's adjuvant.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis
      (MS). However, MS is a chronic, relapsing and demyelinating disease, whereas EAE
      in rats is typically a brief and monophasic disorder showing little
      demyelination. We demonstrate here that DA rats develop severe, protracted and
      relapsing EAE (SPR-EAE) after a subcutaneous immunization at the tail base with
      syngeneic spinal cord and incomplete Freund's adjuvant (IFA). The neurological
      deficits were accompanied by demyelinating inflammatory lesions in the spinal
      cord, with infiltrating T lymphocytes and perivascular deposition of
      immunoglobulins and complement. The induction of SPR-EAE was associated with
      humoral autoreactivity to myelin oligodendrocyte glycoprotein (MOG) and cellular
      autoreactivity to the rat myelin basic protein (MBP) peptides 69-87 and 87-101.
      These two peptides, as well as whole rat MBP, were encephalitogenic. In
      conclusion, we believe that the presently described demyelinating SPR-EAE
      represents a useful model for MS.

PMID- 8550818
TI  - Stimulation of the sphingomyelin pathway induces interleukin-6 gene expression in
      human astrocytoma cells.
AB  - Interleukin-6 (IL-6) has previously been shown to participate in
      neurodegenerative processes including Alzheimer's disease. However, the
      mechanisms leading to increased IL-6 expression in the brain remain largely
      unknown. We have studied the effects of synthetic ceramides and sphingomyelinase
      as possible regulators of IL-6 gene expression in a human astrocytoma cell line.
      The synthetic ceramides C2- and C6-ceramide as well as the enzyme
      sphingomyelinase were able to induce IL-6 gene transcription and protein
      synthesis in a dose-dependent manner with maximal IL-6 mRNA levels being reached
      after 4 h of ceramide treatment. We propose that the sphingomyelin pathway is
      part of the signal transduction cascade leading to IL-6 gene expression in
      astrocytes, and that this pathway may be involved in IL-6-mediated
      neurodegenerative processes.

PMID- 8550819
TI  - The times they are still a'changing: keeping up with the times.

PMID- 8550821
TI  - IgG antiendothelial cell autoantibodies from scleroderma patients induce
      leukocyte adhesion to human vascular endothelial cells in vitro. Induction of
      adhesion molecule expression and involvement of endothelium-derived cytokines.
AB  - IgG autoantibodies that bind human endothelial cells (AECA) were detected by
      ELISA in 30 of 42 samples of sera from patients with scleroderma. Pretreatment of
      human umbilical vein endothelial cells with AECA-positive scleroderma sera, or
      IgG purified from these sera, led to a dose- and time-dependent increase in the
      ability of the cells to bind human U937 monocytic cells. Threshold-active IgG
      concentrations were 1-10 micrograms/ml; effects were significant after 3 h and
      maximal after 6-12 h. IgG from AECA-negative sera or normal sera were without
      effect. Increased adhesion of U937 cells was accompanied by increased expression
      of endothelial intercellular adhesion molecule-1, vascular cell adhesion molecule
      1, and E-selectin. Transfer of endothelial cell-conditioned media after
      pretreatment with AECA and immunodepletion of IgG demonstrated the presence of
      transferable activity that mimicked the effects of AECA. Treatment with
      neutralizing anticytokine antibodies indicated that IL-1, generated by the
      endothelial cells in response to AECA, was involved in the upregulation of
      adhesion molecules and U937 cell adhesion. We conclude that AECA can play a
      pathogenic role in scleroderma by activating endothelial cells, in part due to
      autocrine or paracrine actions of IL-1.

PMID- 8550820
TI  - Increased delta aminolevulinic acid and decreased pineal melatonin production. A
      common event in acute porphyria studies in the rat.
AB  - Tryptophan (TRP) is the precursor of melatonin, the primary secretory product of
      the pineal gland. Hepatic heme deficiency decreases the activity of liver
      tryptophan pyrrolase, leading to increased plasma TRP and serotonin. As a
      paradox, patients with attacks of acute intermittent porphyria (AIP), exhibit low
      nocturnal plasma melatonin levels. This study using a rat experimental model was
      designed to produce a pattern of TRP and melatonin production similar to that in
      AIP patients. Pineal melatonin production was measured in response to: (a) a heme
      synthesis inhibitor, succinylacetone, (b) a heme precursor, delta-aminolevulinic
      acid (Ala), (c) a structural analogue of Ala, gamma-aminobutyric acid. Studies
      were performed in intact rats, perifused pineal glands, and pinealocyte cultures.
      Ala, succinylacetone, and gamma-aminobutyric acid significantly decreased plasma
      melatonin levels independently of blood TRP concentration. In the pineal gland,
      the key enzyme activities of melatonin synthesis were unchanged for hydroxyindole
      O-methyltransferase and decreased for N-acetyltransferase. Our results strongly
      suggest that Ala overproduced by the liver acts by mimicking the effect of gamma
      aminobutyric acid on pineal melatonin in AIP. They also support the view that Ala
      acts as a toxic element in the pathophysiology of AIP.

PMID- 8550822
TI  - Role of angiotensin II in dietary modulation of rat late distal tubule
      bicarbonate flux in vivo.
AB  - We have reported that overnight fasting stimulates bicarbonate reabsorption
      (JtCo2) in rat distal tubules. The present in vivo microperfusion studies
      evaluated the hypothesis that endogenous angiotensin II (AII) mediates this
      response. Rat late distal (LD) tubules were perfused at 8 nl/min in vivo with a
      hypotonic solution containing 28 mM bicarbonate. In overnight-fasted rats, LD
      JtCO2 was significantly higher than in normally fed rats (50 +/- 4 vs. 16 +/- 6
      pmol/min.mm, P < 0.05). When overnight-fasted rats were salt-loaded, JtCO2 fell
      significantly (38 +/- 3 pmol/min.mm, P < 0.05). Conversely, in fed rats ingesting
      a zero-salt diet, JtCO2 increased three-fold (45 +/- 5 pmol/min.mm, P < 0.05).
      Enalaprilat infusion (0.25 micrograms/kg body wt, intravenously), in these zero
      salt and overnight-fasted rats, reduced LD JtCO2 values to normal. Further,
      infusion of losartan (5 mg/kg body wt, intravenously), the specific AII AT1
      receptor blocker, reduced JtCO2 in overnight-fasted rats by two-thirds (16 +/- 4
      pmol/min.mm, P < 0.05). Finally, we perfused 10(-11) M AII intraluminally with
      and without 10(-6) M losartan: AII increased JtCO2 to 45 +/- 6 pmol/min.mm, equal
      to the zero-salt flux. This was completely abrogated by simultaneous losartan
      perfusion. Therefore, these results suggest that AII is an in vivo stimulator of
      late distal tubule bicarbonate reabsorption.

PMID- 8550823
TI  - Direct assessment of liver glycogen storage by 13C nuclear magnetic resonance
      spectroscopy and regulation of glucose homeostasis after a mixed meal in normal
      subjects.
AB  - Despite extensive recent studies, understanding of the normal postprandial
      processes underlying immediate storage of substrate and maintenance of glucose
      homeostasis in humans after a mixed meal has been incomplete. The present study
      applied 13C nuclear magnetic resonance spectroscopy to measure sequential changes
      in hepatic glycogen concentration, a novel tracer approach to measure
      postprandial suppression of hepatic glucose output, and acetaminophen to trace
      the pathways of hepatic glycogen synthesis to elucidate the homeostatic
      adaptation to the fed state in healthy human subjects. After the liquid mixed
      meal, liver glycogen concentration rose from 207 +/- 22 to 316 +/- 19 mmol/liter
      at an average rate of 0.34 mmol/liter per min and peaked at 318 +/- 31 min,
      falling rapidly thereafter (0.26 mmol/liter per min). The mean increment at peak
      represented net glycogen synthesis of 28.3 +/- 3.7 g (approximately 19% of meal
      carbohydrate content). The contribution of the direct pathway to overall glycogen
      synthesis was 46 +/- 5 and 68 +/- 8% between 2 and 4 and 4 and 6 h, respectively.
      Hepatic glucose output was completely suppressed within 30 min of the meal. It
      increased steadily from 60 to 255 min from 0.31 +/- 32 to 0.49 +/- 18 mg/kg per
      min then rapidly returned towards basal levels (1.90 +/- 0.04 mg/kg per min).
      This pattern of change mirrored precisely the plasma glucagon/insulin ratio.
      These data provide for the first time a comprehensive picture of normal
      carbohydrate metabolism in humans after ingestion of a mixed meal.

PMID- 8550824
TI  - Elimination of the action of glucagon-like peptide 1 causes an impairment of
      glucose tolerance after nutrient ingestion by healthy baboons.
AB  - Glucagon-like peptide 1 (GLP-1) is an insulinotropic hormone released after
      nutrient ingestion which is known to augment insulin secretion, inhibit glucagon
      release, and promote insulin-independent glucose disposition. To determine the
      overall effect of GLP-1 on glucose disposition after a meal we studied a group of
      healthy, conscious baboons before and after intragastric glucose administration
      during infusions of saline, and two treatments to eliminate the action of GLP-1:
      (a) exendin-[9-39] (Ex-9), a peptide receptor antagonist of GLP-1; or (b) an anti
      GLP-1 mAb. Fasting concentrations of glucose were higher during infusion of Ex-9
      than during saline (4.44 +/- 0.05 vs. 4.16 +/- 0.05 mM, P < 0.01), coincident
      with an elevation in the levels of circulating glucagon (96 +/- 10 vs. 59 +/- 3
      ng/liter, P < 0.02). The postprandial glycemic excursions during administration
      of Ex-9 and mAb were greater than during the control studies (Ex-9 13.7 +/- 2.0
      vs. saline 10.0 +/- 0.8 mM, P = 0.07; and mAb 13.6 +/- 1.2 vs. saline 10.6 +/-
      0.9 mM, P = 0.044). The increments in insulin levels throughout the absorption of
      the glucose meal were not different for the experimental and control conditions,
      but the insulin response in the first 30 min after the glucose meal was
      diminished significantly during treatment with Ex-9 (Ex-9 761 +/- 139 vs. saline
      1,089 +/- 166 pM, P = 0.044) and was delayed in three of the four animals given
      the neutralizing antibody (mAb 946 +/- 262 vs. saline 1,146 +/- 340 pM). Thus,
      elimination of the action of GLP-1 impaired the disposition of an intragastric
      glucose meal and this was at least partly attributable to diminished early
      insulin release. In addition to these postprandial effects, the concurrent
      elevation in fasting glucose and glucagon during GLP-1 antagonism suggests that
      GLP-1 may have a tonic inhibitory effect on glucagon output. These findings
      demonstrate the important role of GLP-1 in the assimilation of glucose absorbed
      from the gut.

PMID- 8550826
TI  - Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and
      postmenopausal women.
AB  - Although bone loss around the time of menopause is driven by estrogen deficiency,
      the roles of estrogens and androgens in the preservation of skeletal mass at
      other stages of life are less well understood. To address this issue we studied
      231 women between the ages of 32 and 77 with multiple measurements of sex
      steroids and bone mass over a period of 2-8 yr. In all women bone mass was
      negatively associated with concentrations of sex-hormone binding globulin, and
      positively associated with weight. Bone loss occurred from all skeletal sites in
      peri- and postmenopausal women, but premenopausal women lost bone only from the
      hip (-0.3%/yr) and had positive rates of change in the radius and spine. Bone
      loss was significantly associated with lower androgen concentrations in
      premenopausal women, and with lower estrogens and androgens in peri- and
      postmenopausal women. Sex steroids are important for the maintenance of skeletal
      integrity before menopause, and for as long as 20-25 yr afterwards.

PMID- 8550825
TI  - G-protein coupled and tyrosine kinase receptors: evidence that activation of the
      insulin-like growth factor I receptor is required for thrombin-induced
      mitogenesis of rat aortic smooth muscle cells.
AB  - IGF I is an ubiquitous peptide that activates a membrane tyrosine kinase receptor
      and has autocrine/paracrine effects on vascular smooth muscle cells. Thrombin
      activates a G-protein coupled receptor and is also a mitogen for vascular smooth
      muscle cells. To assess the potential role of IGF I as a mediator of thrombin's
      effects, we characterized expression of IGF I and of its receptor on vascular
      smooth muscle cells exposed to thrombin. Thrombin dose-dependently decreased IGF
      I mRNA levels and caused a delayed decrease in IGF I secretion from vascular
      smooth muscle cells. This effect was mimicked by the hexapeptide SF-FLRN (that
      functions as a tethered ligand) and was inhibited by hirudin. In contrast,
      thrombin doubled IGF I receptor density on vascular smooth muscle cells, without
      altering binding affinity (Kd). An anti-IGF I antiserum markedly reduced thrombin
      induced DNA synthesis, whereas nonimmune serum and an anti-fibroblast growth
      factor antibody were without effect. Cell counts confirmed these results.
      Downregulation of IGF I receptors by antisense phosphorothioate oligonucleotides
      likewise markedly inhibited thrombin-induced DNA synthesis. These data
      demonstrate that a functional IGF I-IGF I receptor pathway is essential for
      thrombin-induced mitogenic signaling and support the concept of cross talk
      between G-protein coupled and tyrosine kinase receptors.

PMID- 8550827
TI  - Induction of cyclin A gene expression by homocysteine in vascular smooth muscle
      cells.
AB  - Homocysteine is an important and independent risk factor for arteriosclerosis. We
      showed previously that homocysteine stimulates vascular smooth muscle cell
      proliferation, a hallmark of arteriosclerosis. We show here that homocysteine and
      serum increased DNA synthesis synergistically in both human and rat aortic smooth
      muscle cells (RASMCs). Treatment of quiescent RASMCs with 1 mM homocysteine or 2%
      calf serum for 36 h increased cyclin A mRNA levels by 8- and 14-fold,
      respectively, whereas homocysteine plus serum increased cyclin A mRNA levels by
      40-fold, indicating a synergistic induction of cyclin A mRNA. Homocysteine did
      not increase the half-life of cyclin A mRNA (2.9 h), but it did increase the
      transcriptional rate of the cyclin A gene in nuclear run-on experiments. The
      positive effect of homocysteine on cyclin A gene transcription was confirmed by
      our finding that homocysteine increased cyclin A promoter activity and ATF
      binding protein levels in RASMCs. Finally, 1 mM homocysteine increased cyclin A
      protein levels and cyclin A-associated kinase activity by threefold. This
      homocysteine-induced expression lesions by promoting proliferation of vascular
      smooth muscle cells.

PMID- 8550828
TI  - Profound induction of hepatic cholesteryl ester transfer protein transgene
      expression in apolipoprotein E and low density lipoprotein receptor gene knockout
      mice. A novel mechanism signals changes in plasma cholesterol levels.
AB  - The plasma cholesteryl ester transfer protein (CETP) mediates the transfer of
      cholesteryl esters from HDL to other lipoproteins and is a key regulated
      component of reverse cholesterol transport. Dietary hypercholesterolemia results
      in increased hepatic CETP gene transcription and higher plasma CETP levels. To
      investigate the mechanisms by which the liver senses hypercholesterolemia, mice
      containing a natural flanking region CETP transgene (NFR-CETP transgene) were
      bred with apo E or LDL receptor gene knockout mice (E0 or LDLr0 mice). Compared
      to NFR-CETP transgenic (Tg) mice with intact apo E genes, in NFR-CETP Tg/E0 mice
      there was an eightfold induction of plasma CETP levels and a parallel increase in
      hepatic CETP mRNA levels. Other sterol-responsive genes (LDL receptor and
      hydroxymethyl glutaryl CoA reductase) also showed evidence of altered regulation
      with decreased abundance of their mRNAs in the E0 background. A similar induction
      of plasma CETP and hepatic CETP mRNA levels resulted from breeding the NFR-CETP
      transgene into the LDL receptor gene knockout background. When placed on a high
      cholesterol diet, there was a further increase in CETP levels in both E0 and
      LDLr0 backgrounds. In CETP Tg, CETP Tg/E0, and CETP Tg/LDLr0 mice on different
      diets, plasma CETP and CETP mRNA levels were highly correlated with plasma
      cholesterol levels. The results indicate that hepatic CETP gene expression is
      driven by a mechanism which senses changes in plasma cholesterol levels
      independent of apo E and LDL receptors. Hepatic sterol-sensitive genes have
      mechanisms to sense hypercholesterolemia that do not require classical receptor
      mediated lipoprotein uptake.

PMID- 8550829
TI  - Involvement of wound-associated factors in rat brain astrocyte migratory response
      to axonal injury: in vitro simulation.
AB  - The poor ability of mammalian central nervous system (CNS) axons to regenerate
      has been attributed, in part, to astrocyte behavior after axonal injury. This
      behavior is manifested by the limited ability of astrocytes to migrate and thus
      repopulate the injury site. Here, the migratory behavior of astrocytes in
      response to injury of CNS axons in vivo was simulated in vitro using a scratch
      wounded astrocytic monolayer and soluble substances derived from injured rat
      optic nerves. The soluble substances, applied to the scratch-wounded astrocytes,
      blocked their migration whereas some known wound-associated factors such as
      transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor
      (bFGF), epidermal growth factor (EGF), transforming growth factor-alpha (TGF
      alpha), and heparin-binding epidermal growth factor in combination with insulin
      like growth factor-1 (HB-EGF + IGF-1) stimulated intensive migration with
      consequent closure of the wound. Migration was not dominated by proliferating
      cells. Both bFGF and HB-EGF + IGF-1, but not TGF-beta 1, could overcome the
      blocking effect of the optic nerve-derived substances on astrocyte migration. The
      induced migration appeared to involve proteoglycans. It is suggestive that
      appropriate choice of growth factors at the appropriate postinjury period may
      compensate for the endogenous deficiency in glial supportive factors and/or
      presence of glial inhibitory factors in the CNS.

PMID- 8550830
TI  - Inhibition of cyclic 3'-5'-guanosine monophosphate-specific phosphodiesterase
      selectively vasodilates the pulmonary circulation in chronically hypoxic rats.
AB  - While it is known that nitric oxide (NO) is an important modulator of tone in the
      hypertensive pulmonary circulation, the roles of cyclic 3'-5'-guanosine
      monophosphate (cGMP) and cGMP-phosphodiesterase (PDE) are uncertain. We found
      that isolated lung perfusate levels of cGMP were over ninefold elevated in
      hypertensive vs. normotensive control rats. 98-100% of lung cGMP hydrolytic
      activity was cGMP-specific PDE5, with no significant decrease in PDE activity in
      hypertensive lungs, suggesting that the elevation in cGMP was due to accelerated
      production rather than reduced degradation. In pulmonary hypertensive rat lungs,
      in vitro, cGMP-PDE inhibition by E4021[1-(6-chloro-4-(3,4-methylbenzyl) amino
      quinazolin-2-yl)piperdine-4-carboxylate], increased perfusate cGMP threefold,
      reduced hypoxic vasoconstriction by 58 +/- 2%, and reduced baseline pulmonary
      artery pressure by 37 +/- 5%. In conscious, pulmonary hypertensive rats,
      intravenous administration of E4021 reduced hypoxic vasoconstriction by 68 +/-
      8%, pulmonary artery pressure by 12.6 +/- 3.7% and total pulmonary resistance by
      13.1 +/- 6.4%, with no significant effect on cardiac output, systemic pressure,
      and resistance. Comparison of E4021 to inhaled nitric oxide demonstrated that
      cGMP-PDE inhibition was as selective and as effective as inhaled NO.

PMID- 8550831
TI  - Mechanism of impaired glucose-potentiated insulin secretion in diabetic 90%
      pancreatectomy rats. Study using glucagonlike peptide-1 (7-37).
AB  - Chronic hyperglycemia causes a near-total disappearance of glucose-induced
      insulin secretion. To determine if glucose potentiation of nonglucose
      secretagogues is impaired, insulin responses to 10(-9) M glucagonlike peptide-1
      (GLP-1) (7-37) were measured at 2.8, 8.3, and 16.7 mM glucose with the in vitro
      perfused pancreas in rats 4-6 wk after 90% pancreatectomy (Px) and sham-operated
      controls. In the controls, insulin output to GLP-1 was > 100-fold greater at 16.7
      mM glucose versus 2.8 mM glucose. In contrast, the increase was less than
      threefold in Px, reaching an insulin response at 16.7 mM glucose that was 10 +/-
      2% of the controls, well below the predicted 35-40% fractional beta-cell mass in
      these rats. Px and control rats then underwent a 40-h fast followed by pancreas
      perfusion using a protocol of 20 min at 16.7 mM glucose followed by 15 min at
      16.7 mM glucose/10(-9) M GLP-1. In control rats, fasting suppressed insulin
      release to high glucose (by 90%) and to GLP-1 (by 60%) without changing the
      pancreatic insulin content. In contrast, in Px the insulin response to GLP-1
      tripled in association with a threefold increase of the insulin content, both now
      being twice normal when stratified for the fractional beta-cell mass. The
      mechanism of the increased pancreas insulin content was investigated by assessing
      islet glucose metabolism and proinsulin biosynthesis. In controls with fasting,
      both fell 30-50%. In Px, the degree of suppression with fasting was similar, but
      the attained levels both exceeded those of the controls because of higher
      baseline (nonfasted) values. In summary, chronic hyperglycemia is associated with
      a fasting-induced paradoxical increase in glucose-potentiated insulin secretion.
      In Px rats, the mechanism is an increase in the beta-cell insulin stores, which
      suggests a causative role for a lowered beta-cell insulin content in the impaired
      glucose-potentiation of insulin secretion.

PMID- 8550832
TI  - Heparin-binding secretory transforming gene (hst) facilitates rat lactotrope cell
      tumorigenesis and induces prolactin gene transcription.
AB  - We have shown previously that human prolactinomas express transforming sequences
      of the heparin-binding secretory transforming gene (hst) which encodes fibroblast
      growth factor-4 (FGF-4). To elucidate the role of hst in pituitary tumorigenesis
      we treated primary rat pituitary and pituitary tumor cell cultures with
      recombinant FGF-4 and also stably transfected pituitary cell lines with full
      length human hst cDNA. Transfectants were screened for hst mRNA expression and
      FGF-4 production. FGF-4 (0.1-50 ng/ml) caused a dose-dependent 2.5-fold increase
      of prolactin (PRL) secretion (P < 0.001) in GH4 cells and up to 60% (P < 0.05) in
      primary cultures, while decreasing growth hormone release (P < 0.001). GH4 hst
      transfectants displayed markedly enhanced basal PRL secretion (threefold, P <
      0.001) and also proliferated faster (P < 0.001). FGF-4 treatment of wild-type GH4
      cells, transiently transfected with an expression construct (rPRL.luc) containing
      a luciferase reporter driven by the rPRL promoter, resulted in a dose-dependent
      increase of up to 3.3-fold in PRL transcriptional activity. Tumors derived from
      in vivo subcutaneous injection of GH4 hst-transfected cells strongly expressing
      FGF-4 grew more aggressively as assessed by histologic invasiveness and
      proliferating cell nuclear antigen staining (P < 0.01). The results indicate that
      hst overexpression mediates lactotrope tumor growth and potently stimulates PRL
      synthesis. Thus, hst may directly facilitate prolactinoma development via
      paracrine or autocrine action of its secreted protein, FGF-4.

PMID- 8550834
TI  - Molecular medicine in genetically engineered animals: series introduction.

PMID- 8550833
TI  - A single strand conformation polymorphism study of CD40 ligand. Efficient
      mutation analysis and carrier detection for X-linked hyper IgM syndrome.
AB  - Mutations in the gene for CD40 ligand are responsible for the X-linked form of
      hyper IgM syndrome. However, no clinical or laboratory findings that reliably
      distinguish X-linked disease from other forms of hyper IgM syndrome have been
      reported, nor are there tests available that can be used to confidently provide
      carrier detection. To identify efficiently mutations in the gene for CD40 ligand,
      eight pairs of PCR primers that could be used to screen genomic DNA by single
      strand conformation polymorphism (SSCP) were designed. 11 different mutations
      were found in DNA from all 13 patients whose activated T cells failed to bind a
      recombinant CD40 construct. The exact nature of four of these mutations, a
      deletion and three splice defects, could not be determined by cDNA sequencing. In
      addition, SSCP analysis permitted rapid carrier detection in two families in whom
      the source of the mutation was most likely a male with gonadal chimerism who
      passed the disorder on to some but not all of his daughters. These studies
      document the utility of SSCP analysis for both mutation detection and carrier
      detection in X-linked hyper IgM syndrome.

PMID- 8550835
TI  - Maternal vasoactive intestinal peptide and the regulation of embryonic growth in
      the rodent.
AB  - Vasoactive intestinal peptide (VIP) has been shown to regulate early
      postimplantation growth in rodents through central nervous system receptors.
      However, the source of VIP mediating these effects is unknown. Although VIP
      binding sites are present prenatally, VIP mRNA was not detected in the rat
      central nervous system before birth and was detected in the periphery only during
      the last third of pregnancy. In the present study, the embryonic day (E11) rat
      embryo/trophoblast was shown to have four times the VIP concentration of the E17
      fetus and to have VIP receptors in the central nervous system. However, no VIP
      mRNA was detected in the E11 rat embryo or embryonic membranes by in situ
      hybridization or reverse transcriptase-PCR. RIA of rat maternal serum revealed a
      peak in VIP concentration at days E10-E12 of pregnancy, with VIP rising to levels
      6-10-fold higher than during the final third of pregnancy. After intravenous
      administration of radiolabeled VIP to pregnant female mice, undegraded VIP was
      found in the E10 embryo. These results suggest that maternal tissues may provide
      neuroendocrine support for embryonic growth through a surge of VIP during early
      postimplantation development in the rodent.

PMID- 8550836
TI  - Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery
      occlusion. Role of neutrophil adhesion in the pathogenesis of stroke.
AB  - Acute neutrophil (PMN) recruitment to postischemic cardiac or pulmonary tissue
      has deleterious effects in the early reperfusion period, but the mechanisms and
      effects of neutrophil influx in the pathogenesis of evolving stroke remain
      controversial. To investigate whether PMNs contribute to adverse neurologic
      sequelae and mortality after stroke, and to study the potential role of the
      leukocyte adhesion molecule intercellular adhesion molecule-1 (ICAM-1) in the
      pathogenesis of stroke, we used a murine model of transient focal cerebral
      ischemia consisting of intraluminal middle cerebral artery occlusion for 45 min
      followed by 22 h of reperfusion. PMN accumulation, monitored by deposition of
      111In-labeled PMNs in postischemic cerebral tissue, was increased 2.5-fold in the
      ipsilateral (infarcted) hemisphere compared with the contralateral (noninfarcted)
      hemisphere (P < 0.01). Mice immunodepleted of neutrophils before surgery
      demonstrated a 3.0-fold reduction in infarct volumes (P < 0.001), based on
      triphenyltetrazolium chloride staining of serial cerebral sections, improved
      ipsilateral cortical cerebral blood flow (measured by laser Doppler), and reduced
      neurological deficit compared with controls. In wild-type mice subjected to 45
      min of ischemia followed by 22 h of reperfusion, ICAM-1 mRNA was increased in the
      ipsilateral hemisphere, with immunohistochemistry localizing increased ICAM-1
      expression on cerebral microvascular endothelium. The role of ICAM-1 expression
      in stroke was investigated in homozygous null ICAM-1 mice (ICAM-1 -/-) in
      comparison with wild-type controls (ICAM-1 +/+). ICAM-1 -/- mice demonstrated a
      3.7-fold reduction in infarct volume (P < 0.005), a 35% increase in survival (P <
      0.05), and reduced neurologic deficit compared with ICAM-1 +/+ controls. Cerebral
      blood flow to the infarcted hemisphere was 3.1-fold greater in ICAM-1 -/- mice
      compared with ICAM-1 +/+ controls (P < 0.01), suggesting an important role for
      ICAM-1 in the genesis of postischemic cerebral no-reflow. Because PMN-depleted
      and ICAM-1-deficient mice are relatively resistant to cerebral ischemia
      reperfusion injury, these studies suggest an important role for ICAM-1-mediated
      PMN adhesion in the pathophysiology of evolving stroke.

PMID- 8550837
TI  - Allogeneic hematolymphoid microchimerism and prevention of autoimmune disease in
      the rat. A relationship between allo- and autoimmunity.
AB  - Conventional allogeneic bone marrow transplantation after myeloablation can
      prevent experimental autoimmunity and has been proposed as treatment for humans.
      However, trace populations of donor hematolymphoid cells persisting in solid
      organ allograft recipients have been associated in some circumstances with
      therapeutic effects similar to replacement of the entire bone marrow. We
      therefore examined whether inducing hematolymphoid microchimerism without
      myeloablation could confer the ability to resist mercuric chloride (HgCl2)
      induced autoimmunity. Brown-Norway (BN) rats were pretreated with a syngeneic or
      allogeneic bone marrow infusion under transient FK506 immunosuppression before
      receiving HgCl2. They were compared with BN rats receiving either no pretreatment
      (naive) or FK506 alone. Administration of HgCl2 to naive BN rats induced marked
      autoantibody production, systemic vasculitis and lymphocytic infiltration of the
      kidneys, liver and skin in all of the animals and a 47% mortality. In contrast,
      BN rats pretreated with HgCl2-resistant allogeneic Lewis bone marrow and
      transient FK506 showed less clinical disease and were completely protected from
      mortality. More specifically, IgG anti-laminin autoantibody production was
      decreased by 40% (P < 0.05), and there was less histopathological tissue injury
      (P < 0.005), less in vitro autoreactivity (P < 0.05), less of an increase in
      class II MHC expression on B cells (P < 0.01), and 22% less weight loss (P <
      0.01), compared with controls. Protection from the experimental autoimmunity was
      associated with signs of low grade activation of the BN immune system, which
      included: increased numbers of circulating B and activated T cells before
      administration of HgCl2, and less autoreactivity and spontaneous proliferation in
      vitro after HgCl2.

PMID- 8550838
TI  - Vitamin C improves endothelium-dependent vasodilation in patients with non
      insulin-dependent diabetes mellitus.
AB  - Endothelium-dependent vasodilation is impaired in humans with diabetes mellitus.
      Inactivation of endothelium-derived nitric oxide by oxygen-derived free radicals
      contributes to abnormal vascular reactivity in experimental models of diabetes.
      To determine whether this observation is relevant to humans, we tested the
      hypothesis that the antioxidant, vitamin C, could improve endothelium-dependent
      vasodilation in forearm resistance vessels of patients with non-insulin-dependent
      diabetes mellitus. We studied 10 diabetic subjects and 10 age-matched,
      nondiabetic control subjects. Forearm blood flow was determined by venous
      occlusion plethysmography. Endothelium-dependent vasodilation was assessed by
      intraarterial infusion of methacholine (0.3-10 micrograms/min). Endothelium
      independent vasodilation was measured by intraarterial infusion of nitroprusside
      (0.3-10 micrograms/min) and verapamil (10-300 micrograms/min). Forearm blood flow
      dose-response curves were determined for each drug before and during concomitant
      intraarterial administration of vitamin C (24 mg/min). In diabetic subjects,
      endothelium-dependent vasodilation to methacholine was augmented by simultaneous
      infusion of vitamin C (P = 0.002); in contrast, endothelium-independent
      vasodilation to nitroprusside and to verapamil were not affected by concomitant
      infusion of vitamin C (P = 0.9 and P = 0.4, respectively). In nondiabetic
      subjects, vitamin C administration did not alter endothelium-dependent
      vasodilation (P = 0.8). We conclude that endothelial dysfunction in forearm
      resistance vessels of patients with non-insulin-dependent diabetes mellitus can
      be improved by administration of the antioxidant, vitamin C. These findings
      support the hypothesis that nitric oxide inactivation by oxygen-derived free
      radicals contributes to abnormal vascular reactivity in diabetes.

PMID- 8550839
TI  - Transient introduction of a foreign gene into healing rat patellar ligament.
AB  - We investigated the in vivo introduction of a reporter gene into healing rat
      patellar ligaments using the hemagglutinating virus of Japan (HVJ)-liposome
      mediated gene transfer method. The mid-portion of the medial half of the patellar
      ligament was cut transversely with a scalpel in 14-wk-old male Wistar rats. A HVJ
      liposome suspension containing beta-galactosidase (beta-gal) cDNA was injected
      directly into the injured site and pooled in the fascial pocket covering the
      injured site 3 d postoperatively. Thereafter, beta-gal-labeled cells were
      observed in the wound site accounting for 3% of the wound cells on the first day,
      2% on the third, 7% on the seventh, 6% on the 14th, 2% on the 28th, and 0.2% on
      the 56th day after injection. The beta-gal-labeled cells were initially localized
      in and adjacent to the wound site, but they were observed spreading into the
      ligament substance away from the wound on the seventh day after injection. On day
      28, beta-gal-labeled cells were observed throughout the length of the ligament
      substance. With double-labeling for marker antigens for monocyte/macrophage (ED
      1) and for collagen I aminopropeptide (pN collagen I), it was revealed that
      fibroblastic (pN collagen I-positive) cells accounted for 63% and
      monocyte/macrophage lineage cells for 32% of the beta-gal-labeled cells in the
      day 7 wound. On day 28, they formed 58 and 35% of the beta-gal-labeled cells in
      the wound, respectively. Thus, we succeeded in introducing the beta-gal gene into
      healing rat patellar ligament. Moreover, labeling of the transfected cells made
      it possible to identify a biological event, namely that the cells in and around
      the wound site infiltrate into the uninjured ligament substance and come to
      populate the whole length of the ligament substance as repair progresses. These
      results suggest that ligament healing may involve not only the repair of the
      wound site itself but also extensive cellular infiltration of ligament substance
      adjacent to the wound.

PMID- 8550840
TI  - Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or
      overexpress the murine plasminogen activator inhibitor-1 gene.
AB  - Impaired fibrinolytic activity within the lung is a common manifestation of acute
      and chronic inflammatory lung diseases. Because the fibrinolytic system is active
      during repair processes that restore injured tissues to normal, reduced
      fibrinolytic activity may contribute to the subsequent development of pulmonary
      fibrosis. To examine the relationship between the fibrinolytic system and
      pulmonary fibrosis, lung inflammation was induced by bleomycin in transgenic mice
      that either overexpressed or were completely deficient in murine plasminogen
      activator inhibitor-1 (PAI-1). 2 wk after 0.075 U of bleomycin, the lungs of
      transgenic mice overexpressing PAI-1 contained significantly more hydroxyproline
      (118 +/- 8 micrograms) than littermate controls (70.5 +/- 8 micrograms, P <
      0.005). 3 wk after administration of a higher dose of bleomycin (0.15 U), the
      lung hydroxyproline content of mice completely deficient in PAI-1 (49 +/- 8
      micrograms) was not significantly different (P = 0.63) than that of control
      animals receiving saline (37 +/- 1 micrograms), while hydroxyproline content was
      significantly increased in heterozygote (77 +/- 12 micrograms, P = 0.06) and wild
      type (124 +/- 19 micrograms, P < 0.001) littermates. These data demonstrate a
      direct correlation between the genetically determined level of PAI-1 expression
      and the extent of collagen accumulation that follows inflammatory lung injury.
      These results strongly support the hypothesis that alterations in fibrinolytic
      activity influence the extent of pulmonary fibrosis that occurs after
      inflammatory injury.

PMID- 8550841
TI  - Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy. Soluble
      receptor for advanced glycation end products blocks hyperpermeability in diabetic
      rats.
AB  - Dysfunctional endothelium is associated with and, likely, predates clinical
      complications of diabetes mellitus, by promoting increased vascular permeability
      and thrombogenicity. Irreversible advanced glycation end products (AGEs),
      resulting from nonenzymatic glycation and oxidation of proteins or lipids, are
      found in plasma, vessel wall, and tissues and have been linked to the development
      of diabetic complications. The principal means through which AGEs exert their
      cellular effects is via specific cellular receptors, one of which, receptor for
      AGE (RAGE), is expressed by endothelium. We report that blockade of RAGE inhibits
      AGE-induced impairment of endothelial barrier function, and reverse, in large
      part, the early vascular hyperpermeability observed in diabetic rats. Inhibition
      of AGE- and diabetes-mediated hyperpermeability by antioxidants, both in vitro
      and in vivo, suggested the central role of AGE-RAGE-induced oxidant stress in the
      development of hyperpermeability. Taken together, these data support the concept
      that ligation of AGEs by endothelial RAGE induces cellular dysfunction, at least
      in part by an oxidant-sensitive mechanism, contributing to vascular
      hyperpermeability in diabetes, and that RAGE is central to this pathologic
      process.

PMID- 8550842
TI  - Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic
      systems in interleukin 6 transgenic mice.
AB  - The muscles of IL-6 transgenic mice suffer from atrophy. Experiments were carried
      out on these transgenic mice to elucidate activation of proteolytic systems in
      the gastrocnemius muscles and blockage of this activation by treatment with the
      anti-mouse IL-6 receptor (mIL-6R) antibody. Muscle atrophy observed in 16-wk-old
      transgenic mice was completely blocked by treatment with the mIL-6R antibody. In
      association with muscle atrophy, enzymatic activities and mRNA levels of
      cathepsins (B and L) and mRNA levels of ubiquitins (poly- and mono-ubiquitins)
      increased, whereas the mRNA level of muscle-specific calpain (calpain 3)
      decreased. All these changes were completely eliminated by treatment with the mIL
      6R antibody. This IL-6 receptor antibody could, therefore, be effective against
      muscle wasting in sepsis and cancer cachexia, where IL-6 plays an important role.

PMID- 8550843
TI  - The potent anti-Staphylococcus aureus activity of a sterile rabbit inflammatory
      fluid is due to a 14-kD phospholipase A2.
AB  - The cell-free fluid (ascitic fluid, AF) of a sterile inflammatory peritoneal
      exudate elicited in rabbits is potently bactericidal for complement-resistant
      gram-negative as well as gram-positive bacterial species. This activity is absent
      in plasma. We now show that essentially all activity in AF against Staphylococcus
      aureus is attributable to a group II 14-kD phospholipase A2 (PLA2), previously
      purified from AF in this laboratory. Antistaphylococcal activity of purified PLA2
      and of whole AF containing a corresponding amount of PLA2 was comparable and
      blocked by anti-AF-PLA2 serum. At concentrations present in AF (approximately 10
      nM), AF PLA2 kills > 2 logs of 10(6) S. aureus/ml, including methicillin
      resistant clinical isolates, and other species of gram-positive bacteria. Human
      group II PLA2 displays similar bactericidal activity toward S. aureus (LD90
      approximately 1-5 nM), whereas 14-kD PLA2 from pig pancreas and snake venom are
      inactive even at micromolar doses. Bacterial killing by PLA2 requires Ca2+ and
      catalytic activity and is accompanied by bacterial phospholipolysis and
      disruption of the bacterial cell membrane and cell wall. These findings reveal
      that group II extracellular PLA2, the function of which at inflammatory sites has
      been unclear, is an extraordinarily potent endogenous antibiotic against S.
      aureus and other gram-positive bacteria.

PMID- 8550844
TI  - Human diabetes associated with defects in nuclear regulatory proteins for the
      insulin receptor gene.
AB  - The control of gene transcription is mediated by sequence-specific DNA-binding
      proteins (trans-acting factors) that bind to upstream regulatory elements (cis
      elements). We have previously identified two DNA-binding proteins that
      specifically interact with two unique AT-rich sequences of the 5' regulatory
      region of the insulin receptor gene which have in vivo promoter activity. Herein
      we have investigated the expression of these DNA-binding proteins in cells from
      two unrelated patients with insulin resistance and non-insulin-dependent diabetes
      mellitus. In these patients, the insulin receptor gene was normal. In EBV
      transformed lymphoblasts from both patients, insulin receptor mRNA levels and
      insulin receptor expression were decreased. The expression of nuclear-binding
      proteins for the 5' regulatory region of the insulin receptor gene was markedly
      reduced, and this defect paralleled the decrease in insulin receptor protein
      expression. These studies indicate that DNA-binding proteins to the regulatory
      region of the insulin receptor gene are important for expression of the insulin
      receptor. Further, they suggest that in affected individuals, defects in the
      expression of these proteins may cause decreased insulin receptor expression and
      insulin resistance.

PMID- 8550845
TI  - Na+/myo-inositol transport is regulated by basolateral tonicity in Madin-Darby
      canine kidney cells.
AB  - We investigated the effects of change in basolateral osmolality on Na(+)
      dependent myo-inositol uptake in Madin-Darby canine kidney cells to test our
      hypothesis that the Na+/myo-inositol transporter (SMIT), an osmolyte transporter,
      is mainly regulated by osmolality on the basolateral surface. A significant
      osmotic gradient between both sides of the epithelium persisted at least 10 h
      after basolateral osmolality was increased. [3H]myo-inositol uptake increased in
      a basolateral osmolality-dependent manner. The magnitude of the increase is
      comparable to that for making both sides hypertonic. Apical hypertonicity also
      increased the uptake on the basal side, but the magnitude of the increase was
      significantly smaller than the basolateral or both sides hypertonicity. Betaine
      gamma-amino-n-butyric acid transporter activity, measured by [3H]gamma-amino-n
      butyric uptake, showed a pattern similar to SMIT activity in response to
      basolateral hypertonicity. The most plausible explanation for the polarized
      effect of hypertonicity is that the basal membrane is much more water permeable
      than the apical membrane. These results seem to be consistent with the
      localization and regulation of the SMIT in vivo.

PMID- 8550846
TI  - Red cell membrane remodeling in sickle cell anemia. Sequestration of membrane
      lipids and proteins in Heinz bodies.
AB  - In red cells from patients with sickle cell anemia, hemoglobin S denatures and
      forms Heinz bodies. Binding of Heinz bodies to the inner surface of the sickle
      cell membrane promotes clustering and colocalization of the membrane protein band
      3, outer surface-bound autologous IgG and, to some extent, the membrane proteins
      glycophorin and ankyrin. Loss of transbilayer lipid asymmetry is also found in
      certain populations of sickle red cells. The lateral distribution of sickle cell
      membrane lipids has not been examined, however. In this report, we examine by
      fluorescence microscopy the incorporation and distribution of the fluorescent
      phospholipid analogues 7-nitro-2,1,3-benzoxadiazol-4-yl (NBD)-phosphatidylserine
      and NBD-phosphatidylcholine in sickle red cells. Both phospholipid analogues are
      observed to accumulate prominently at sites of Heinz bodies. Accumulation at
      sites of Heinz bodies is also shown by 1,'1-dihexadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate, a fluorescent lipid analogue that
      readily crosses membranes, but not by fluorescein-phosphatidylethanolamine, an
      analogue that is localized to the outer leaflet of the membrane. Double labeling
      and confocal microscopy techniques show that NBD-lipids, band 3 protein, protein
      4.1, ankyrin, and spectrin are all sequestered within sickle red cells and
      colocalized at sites of Heinz bodies. We propose that Heinz bodies provide a
      hydrophobic surface on which sickle red cell membrane lipids and proteins are
      sequestered.

PMID- 8550847
TI  - Gene modification via "plug and socket" gene targeting.

PMID- 8550848
TI  - Distribution and regulation of plasminogen activator inhibitor-1 in murine
      adipose tissue in vivo. Induction by tumor necrosis factor-alpha and
      lipopolysaccharide.
AB  - Although elevated plasma plasminogen activator inhibitor 1 (PAI-1) is associated
      with obesity, very little is known about its tissue or cellular origin, or about
      the events that lead to increased PAI-1 levels under obese conditions. Since TNF
      alpha is increased in rodents both during obesity and in response to endotoxin
      treatment, we examined the effects of these agents on PAI-1 gene expression in
      the adipose tissue of CB6 mice. In untreated mice, PAI-1 mRNA was detected in
      both mature adipocytes and in stromal vascular cells. Both TNF-alpha and
      endotoxin significantly increased PAI-1 mRNA in the adipose tissue, peaking at 3
      8 h. In situ hybridization analysis of adipose tissue from untreated mice
      revealed a weak signal for PAI-1 mRNA only in the smooth muscle cells within the
      vascular wall. In contrast, after endotoxin or TNF-alpha treatment, PAI-1 mRNA
      also was detected in adipocytes and in adventitial cells of vessels. Endotoxin
      also induced PAI-1 in endothelial cells, while TNF-alpha additionally induced it
      in smooth muscle cells. Mature 3T3-L1 adipocytes in culture also expressed PAI-1
      mRNA, and its rate of synthesis was also upregulated by TNF-alpha. These studies
      suggest that the adipose tissue itself may be an important contributor to the
      elevated PAI-1 levels observed in the plasma under obese conditions.

PMID- 8550849
TI  - Functional magnetic resonance imaging reveals brain regions mediating the
      response to resistive expiratory loads in humans.
AB  - Obstructive lung disease is the most common form of respiratory disturbance.
      However, the location of brain structures underlying the ventilatory response to
      resistive expiratory loads is unknown in humans. To study this issue, midsagittal
      magnetic resonance images were acquired in eight healthy volunteers before and
      after application of a moderate resistive expiratory load (30 cmH2O/liter/s),
      using functional magnetic resonance imaging (fMRI) strategies (1.5-T magnetic
      resonance; repetition time: 72 ms; echo time: 45 ms; flip angle: 30 degrees;
      field of view: 26 cm; slice thickness: 5 mm; 128 x 256 x 1 number of
      excitations). Digital image subtractions and region of interest analyses revealed
      significant increases in fMRI signal intensity in discrete areas of the ventral
      medulla, ventral and dorsal pontomedullary structures, basal forebrain, and
      cerebellum. Upon load withdrawal, a rapid fMRI signal off-transient occurred in
      all activated sites. Application of an identical load immediately after recovery
      from the initial stimulus resulted in smaller signal increases (P < 0.02).
      Prolongation of load duration was associated with progressive fMRI signal
      decrease across activated regions. In three additional subjects, the threshold
      for significant MRI signal increases was established at expiratory loads > or =
      15 cmH2O/liter/s and was dose dependent with increasing loads. We conclude that
      resistive expiratory loads > or = 15 cmH2O/liter/s elicit regional activation of
      discrete brain locations in humans.

PMID- 8550850
TI  - Modulation of L-selectin ligand expression during an immune response accompanying
      tumorigenesis in transgenic mice.
AB  - Immune surveillance depends on lymphocyte access to tissue. Lymphocytes emigrate
      from blood when adhesion receptors such as L-selectin and the alpha 4 beta 7
      integrin on these cells bind to ligands expressed on venular endothelium. Among
      transgenic mouse lines expressing an oncoprotein (Tag) in islet beta cells, some
      recognize Tag as nonself. In these mice, Tag expression elicits both beta cell
      hyperplasia with subsequent progression to tumors and lymphocytic infiltration.
      Endothelial ligands for L-selectin and alpha 4 beta 7 were upregulated in
      infiltrated islets in these transgenic mice. These ligands were not expressed in
      tumors, which were devoid of lymphocytic infiltration. In contrast, the adhesion
      molecules PECAM-1, ICAM-1, and VCAM-1 were expressed on endothelium in both
      noninfiltrated tumors and infiltrated islets. Thus, upregulation of expression of
      endothelial ligands for L-selectin and alpha 4 beta 7 may contribute to
      autoimmune infiltration. Repression of expression of these same ligands may be
      involved in the failure of tumor immunity.

PMID- 8550851
TI  - Digoxin reduces beta-adrenergic contractile response in rabbit hearts. Ca(2+)
      dependent inhibition of adenylyl cyclase activity via Na+/Ca2+ exchange.
AB  - Whereas mobilization of intracellular Ca2+ stimulates neuronal adenylyl cyclase
      via Ca2+/calmodulin, mobilized Ca2+ directly inhibits adenylyl cyclase in other
      tissues. To determine the physiologic role of the Ca(2+)-dependent interaction
      between Na+/Ca2+ exchange and beta-adrenergic signal transduction in the intact
      heart, digoxin (0.3 mg/kg) was administered intravenously in rabbits. 30 min
      after the administration, digoxin impaired the peak left ventricular dP/dt
      response to dobutamine infusions by up to 38% as compared with control rabbits.
      This impairment was not caused by changes in either beta-adrenergic receptor
      number or in the functional activity of stimulatory guanine nucleotide-binding
      protein. It was associated with 33-36% reductions in basal and stimulated
      adenylyl cyclase activities. Animals treated with calcium gluconate (20 mg/kg/min
      for 30 min) also demonstrated similar reductions in adenylyl cyclase activities.
      In addition, increasing the free Ca2+ concentration progressively inhibited
      adenylyl cyclase activity in the control, digoxin-treated, and calcium gluconate
      treated sarcolemma preparations in vitro. Moreover, digoxin and calcium gluconate
      pretreatment blunted the increase in cAMP in myocardial tissue after dobutamine
      infusion in vivo. Thus, digoxin rapidly reduces beta-adrenergic contractile
      response in rabbit hearts. This reduction may reflect an inhibition of adenylyl
      cyclase by Ca2+ mobilized via Na+/Ca2+ exchange.

PMID- 8550852
TI  - Prolonged postprandial responses of lipids and apolipoproteins in triglyceride
      rich lipoproteins of individuals expressing an apolipoprotein epsilon 4 allele.
AB  - The postprandial responses of apo B48, B100, E and lipids in triglyceride-rich
      lipoproteins (TRL) to a meal containing one-third of daily energy (39% fat
      calories) were compared in normolipidemic young men with apo E3/3 and apo E4/3
      phenotypes. After the two groups consumed a diet rich in polyunsaturated fat for
      15-29 d, their postabsorptive concentrations of TRL triglycerides, apo B48, and
      apo B100 were virtually identical, but their postprandial responses differed. In
      both groups, TRL apo B48 increased at 3 h but returned to postabsorptive values
      at 6 h only in the apo E3/3 group; in the apo E4/3 group the concentration of apo
      B48 at 6 h was 80% higher than postabsorptive values. TRL apo B100 also increased
      at 3 h in the two groups and fell to post-absorptive values at 6 h in the apo
      E3/3 group but remained 51% higher than postabsorptive concentrations in the apo
      E4/3 group; this response was closely coupled to that of TRL cholesterol and apo
      E. These observations suggest that clearance of intestinal and hepatogenous TRL
      remnants is impaired in young men with an apo E4/3 phenotype.

PMID- 8550853
TI  - Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of
      antileukemic effects in vivo. A rationale for high-dose methotrexate.
AB  - Methotrexate (MTX) is one of the most widely used drugs for the treatment of
      childhood acute lymphoblastic leukemia (ALL) and is commonly given in high doses.
      However, the rationale for high-dose MTX (HDMTX) has been challenged recently. To
      determine whether higher MTX polyglutamate (MTXPG) concentrations in ALL blasts
      translate into greater antileukemic effects, 150 children with newly diagnosed
      ALL were randomized to initial treatment with either HDMTX (1,000 mg/m2
      intravenously over 24 h) or lower-dose MTX (30 mg/m2 by mouth every 6 h x 6). ALL
      blasts accumulated higher concentrations of MTXPG and long-chain MTXPG (MTXPGLC)
      after HDMTX (P < 0.00001). Of 101 patients evaluable for peripheral blast
      cytoreduction, MTXPG concentrations were higher in patients whose blast count
      decreased within 24 h (P = 0.005) and in those who had no detectable circulating
      blasts within 4 days (P = 0.004). The extent of inhibition of de novo purine
      synthesis in ALL blasts was significantly related to the blast concentration of
      MTXPGLC (IC95% = 483 pmol/10(9) blasts). The percentage of patients with 44-h
      MTXPGLC exceeding the IC95% was greater after HDMTX (81%) than LDMTX (46%, P <
      0.0001). These data indicate that higher blast concentrations of MTXPG are
      associated with greater antileukemic effects, establishing a strong rationale for
      HD-MTX in the treatment of childhood ALL.

PMID- 8550854
TI  - Comparison of the time courses of insulin and the portal signal on hepatic
      glucose and glycogen metabolism in the conscious dog.
AB  - To investigate the temporal response of the liver to insulin and portal glucose
      delivery, somatostatin was infused into four groups of 42-h-fasted, conscious
      dogs (n = 6/group), basal insulin and glucagon were replaced intraportally, and
      hyperglycemia was created via a peripheral glucose infusion for 90 min (period
      1). This was followed by a 240-min experimental period (period 2) in which
      hyperglycemia was matched to period 1 and either no changes were made (CON), a
      fourfold rise in insulin was created (INS), a portion of the glucose (22.4
      mumol.kg-1.min-1) was infused via the portal vein (Po), or a fourfold rise in
      insulin was created in combination with portal glucose infusion (INSPo). Arterial
      insulin levels were similar in all groups during period 1 (approximately 45 pM)
      and were 45 +/- 9, 154 +/- 20, 43 +/- 7, and 128 +/- 14 pM during period 2 in
      CON, INS, Po, and INSPo, respectively. The hepatic glucose load was similar
      between periods and among groups (approximately 278 mumol.kg-1.min-1). Net
      hepatic glucose output was similar among groups during period 1 (approximately
      0.1 mumol.kg-1.min-1) and did not change significantly in CON during period 2. In
      INS net hepatic glucose uptake (NHGU; mumol.kg-1.min-1) was -3.8 +/- 3.3 at 15
      min of period 2 and did not reach a maximum (-15.9 +/- 6.6) until 90 min. In
      contrast, NHGU reached a maximum of -13.0 +/- 3.7 in Po after only 15 min of
      period 2. In INSPo, NHGU reached a maximum (-23.6 +/- 3.5) at 60 min. Liver
      glycogen accumulation during period 2 was 21 +/- 10, 84 +/- 17, 65 +/- 16, and
      134 +/- 17 mumol/gram in CON, INS, Po, and INSPo, respectively. The increment
      (period 1 to period 2) in the active form of liver glycogen synthase was 0.7 +/-
      0.4, 6.5 +/- 1.2, 2.8 +/- 1.0, and 8.5 +/- 1.3% in CON, INS, Po, and INSPo,
      respectively. Thus, in contrast to insulin, the portal signal rapidly activates
      NHGU. In addition, the portal signal independent of a rise in insulin, can cause
      glycogen accumulation in the liver.

PMID- 8550855
TI  - Gastric emptying and release of incretin hormones after glucose ingestion in
      humans.
AB  - This study investigated in eight healthy male volunteers (a) the gastric emptying
      pattern of 50 and 100 grams of glucose; (b) its relation to the phase of
      interdigestive motility (phase I or II) existing when glucose was ingested; and
      (c) the interplay between gastric emptying or duodenal perfusion of glucose (1.1
      and 2.2 kcal/min; identical total glucose loads as orally given) and release of
      glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1(7
      36)amide (GLP-1), C-peptide, insulin, and plasma glucose. The phase of
      interdigestive motility existing at the time of glucose ingestion did not affect
      gastric emptying or any metabolic parameter. Gastric emptying of glucose
      displayed a power exponential pattern with a short initial lag period. Duodenal
      delivery of glucose was not constant but exponentially declined over time.
      Increasing the glucose load reduced the rate of gastric emptying by 27.5% (P <
      0.05) but increased the fractional duodenal delivery of glucose. Both glucose
      loads induced a fed motor pattern which was terminated by an antral phase III
      when approximately 95% of the meal had emptied. Plasma GLP-1 rose from basal
      levels of approximately 1 pmol/liter of peaks of 3.2 +/- 0.6 pmol/liter with 50
      grams of glucose and of 7.2 +/- 1.6 pmol/liter with 100 grams of glucose. These
      peaks occurred 20 min after glucose intake irrespective of the load. A duodenal
      delivery of glucose exceeding 1.4 kcal/min was required to maintain GLP-1 release
      in contrast to ongoing GIP release with negligibly low emptying of glucose. Oral
      administration of glucose yielded higher GLP-1 and insulin releases but an equal
      GIP release compared with the isocaloric duodenal perfusion. We conclude that (a)
      gastric emptying of glucose displays a power exponential pattern with duodenal
      delivery exponentially declining over time and (b) a threshold rate of gastric
      emptying of glucose must be exceeded to release GLP-1, whereas GIP release is not
      controlled by gastric emptying.

PMID- 8550856
TI  - Intrasulcular laser Doppler readings before and after root planing.
AB  - A reproducible and sensitive laser Doppler periodontal probe has recently been
      developed for intrasulcular measurement of gingival blood flow. The specific aims
      of this investigation were to determine the relation between intrasulcular laser
      Doppler readings (LDR) and traditional diagnostic criteria as well as to evaluate
      the response to root planning in terms of LDR and traditional criteria. LDR and
      clinical measurements (bleeding on probing (BOP), probing depth (PD) and clinical
      attachment loss (CAL) were obtained from 2 healthy and 2 diseased sites in 30
      systemically healthy adult volunteers with localized moderate to advanced
      periodontitis. All 30 subjects were re-examined 1 month following root planing
      while 10 subjects were re-examined at approximately 1 year after treatment.
      Subject-adjusted correlations between pretreatment LDR and PD as well as LDR and
      CAL were 0.74 and 0.71, respectively. 1 month following root planing, the
      diseased sites had undergone a significant reduction in LDR and PD with an
      accompanying gain in CAL. Prior to treatment, 95 of 120 sites (79%) agreed on an
      ordinal classification (high, low) for LDR and BOP. Mantel-Haenszel common odds
      ratios for agreement between LDR and BOP were 9.6 pre-treatment and 4.3 one month
      after treatment. A slight rebound of all measurements was noted in a group of 10
      subjects followed for 1 year. It was concluded that the laser Doppler periodontal
      probe is an unbiased non-invasive method of monitoring the response to
      periodontal therapy.

PMID- 8550857
TI  - Efficacy on supragingival plaque control of cetylpyridinium chloride in a slow
      release dosage form.
AB  - To evaluate the relative efficacy of a non-degradable osmotic slow-release dosage
      form containing 6.6 mg cetylpyridinium chloride (MOTS [Mucosal Oral Therapeutic
      System] CPC) to inhibit new plaque formation and gingivitis, a single-blind,
      randomised, parallel group pilot study was set up. 52 healthy volunteers were
      assigned to receive one of the following treatments for 18 days of non-brushing:
      holding 1 MOTS CPC 2 x daily for 2 h intra-orally, or rinsing 30 s with 15 ml
      Peridex 2 x daily, or dissolve Cepacol (each 1.6 mg CPC) lozenges 2 x daily
      unsupervised. Before the test period, the subjects received a thorough tooth
      cleaning followed by tooth polishing 1 x a week for 3 weeks to achieve clinical
      gingival health. After the start of therapy, the subjects were examined at day 4,
      7 (+/- 2), 14 (+/- 2) and 18 (2 +/-). Relative efficacy was assessed by the
      modified Navy plaque index, the Quigley and Hein index, the planimetric plaque
      index, as well as the papillary marginal gingival index. There was an increase in
      both plaque formation and gingivitis over the 18 +/- 2 day period of nonbrushing
      for all subjects in the study. Peridex was the most effective in inhibiting
      plaque and gingivitis formation over that period of time. There was no difference
      between MOTS CPC and Cepacol at any time point in plaque accumulation and
      gingivitis intensity. Peridex was considered more convenient than MOTS CPC.
      Cepacol resulted in more staining at 18 days than MOTS CPC and Peridex.

PMID- 8550858
TI  - The effect of a commercially available triclosan-containing toothpaste compared
      to a sodium-fluoride-containing toothpaste and a chlorhexidine rinse on 4-day
      plaque regrowth.
AB  - Many compounds could be added to toothpaste to assist plaque inhibition, but
      ionic interactions can cause formulation difficulties. Moreover, the actual
      chemical action of a plaque inhibitory agent added to a toothpaste is difficult
      to assess when the product is used in the conventional manner, i.e., in addition
      to toothbrushing. The non-ionic antimicrobial triclosan has been incorporated in
      toothpastes and shown to have variable plaque inhibitory activity both alone and
      in conjunction with certain polymers or metal ions. Little is known of the
      efficacy of triclosan toothpastes compared to conventional fluoride toothpastes.
      The aim of this study was to compare a commercially available toothpaste
      containing 0.3% triclosan/co-polymer with a sodium fluoride toothpaste for
      chemical plaque inhibitory effects over a 4-day period. The study was designed to
      stratify the relative efficacy plaque inhibitory action of the products,
      comparisons were made with a positive control, chlorhexidine rinse and a negative
      control, saline. The study design was a randomised single blind crossover design
      balanced for first-order carryover. A total of 18 healthy, dentate volunteers
      participated in the study. On day 1 of each period the volunteers suspended
      toothcleaning and rinsed 2 x daily with the allocated mouthrinse or toothpaste
      slurry. On day 5, the plaque on the teeth was disclosed and scored by index and
      area. Increasing plaque scores were in the order chlorhexidine, triclosan
      toothpaste, fluoride toothpaste, and saline. Chlorhexidine was significantly more
      effective than all the other agents tested, and both toothpaste preparations were
      significantly better than the saline rinse. There was no significant difference
      between the two toothpaste rinses. Consistent with other studies the triclosan
      toothpaste offers only moderate plaque inhibitory properties when compared to a
      conventional toothpaste.

PMID- 8550859
TI  - Radiographic alveolar bone loss from posterior teeth in young adults over a 4
      year period.
AB  - The objective of this study was to determine alveolar bone loss from premolar and
      molar teeth in young adults over a 4-year period between the ages of 15-16 years
      and 19-20 years. Pairs of posterior bitewing radiographs from 382 subjects aged
      15-16 years were examined and the height of the alveolar bone adjacent to mesial
      and distal tooth surfaces recorded. Repeat radiographs of the same individuals
      taken 4 years later were then examined and the height of the alveolar bone
      remeasured. Change in bone height over the study period was computed for
      individual sites. Clinical data for the cohort were also obtained at both
      examinations and included plaque score, bleeding on probing and probing depth. Of
      the 3314 sites, 16.7% exhibited bone gain, 4.5% exhibited no change whilst 78.8%
      demonstrated bone loss. The overall mean bone loss for all sites combined was
      0.407 mm. Bone loss than 0.5 mm was found in 36% of sites, bone loss between 0.5
      and 0.99 mm in 33% of sites whilst only 0.5% of sites had bone loss greater than
      2 mm. Only one site had bone loss greater than 3 mm. Bone loss was affected
      significantly by subject (p < 0.001) and by site (p < 0.05) but there was no
      significant effect for tooth type, whether the surface was mesial or distal or
      between quadrants. There was significantly more bone loss from around maxillary
      teeth than mandibular (p < 0.05). There were no significant associations between
      bone loss and plaque score, bleeding on probing, pocket depth, gender or social
      class.

PMID- 8550861
TI  - Periodontal bone loss of teeth with metal posts. A radiographic study.
AB  - Periodontal bone loss was compared in teeth with metal posts and contralateral
      teeth without metal posts by means of intraoral radiographs. 250 subjects with a
      high standard of dental awareness and a great number of teeth retained were
      included in the study. The periodontal bone loss was calculated from the ratio of
      the distance from bone margin to apex (bone height) and the distance from crown
      tip to apex (tooth length). Intra-individual differences between experimental and
      control teeth were statistically analyzed with the Student paired t-test. 96
      subjects (38%) had > or = 1 teeth with root posts. In all, 172 teeth with posts
      were found, i.e., on average 1.8 teeth per subject. The means +/- SEM of the
      ratio bone height to tooth length in experimental and control teeth were 0.52 +/-
      0.007 and 0.56 +/- 0.006, respectively. The difference was statistically highly
      significant (P < 0.001). Statistically significant differences were found for
      incisors, premolars and molars. Regression analysis indicated more severe bone
      loss for teeth with longer posts. The results suggest that the periodontal bone
      support of teeth with metal posts is inferior to that of teeth without metal
      posts.

PMID- 8550860
TI  - Antibody responses to suspected periodontal pathogens in elderly subjects with
      periodontal disease.
AB  - Little is known about the relationship of aging to periodontal disease. The
      immune response undergoes aging-related changes resulting in loss of functional
      capacity. The aim of this study was to investigate the relationship between
      levels of serum IgG antibodies against suspected periodontal pathogenic
      microorganisms to the presence or absence of periodontal disease in an elderly
      (65-75 yrs) population. From this study, we obtained information concerning: (1)
      the ability to differentiate elderly individuals without disease from those with
      disease by their levels of antibodies against periodontal pathogens and (2) which
      periodontal pathogen(s) triggered those responses. IgG anti- Porphyromonas
      gingivalis (strains W83 and 381) levels in the serum of elderly patients with
      severe periodontal disease were the only antibody responses measured which were
      elevated compared to the elderly control group of subjects with no periodontal
      disease. Anti- Prevotella intermedia IgG levels in both elderly patient groups
      were depressed compared to anti- P. intermedia levels in the young normal control
      subjects. Serum IgG antibody levels to six other plaque microorganisms did not
      differentiate between diseased and normal, elderly or young subjects. This data
      suggested that P. gingivalis was associated with periodontal disease in this
      elderly group of individuals and that those elderly individuals were able to
      respond with a normal IgG immune response.

PMID- 8550862
TI  - Putative periodontal pathogens colonizing oral mucous membranes in denture
      wearing subjects with a past history of periodontitis.
AB  - The prevalence of selected putative periodontal pathogens colonizing oral mucous
      membranes was investigated in 26 denture-wearing subjects with a history of
      periodontitis. The microbiota of the oral cavity of these subjects was examined
      on average 9.3 years after extraction (range: 1-40 years). Samples were taken
      from several locations on the oral mucous membranes, from saliva and from plaque
      attached to the upper and lower denture. Actinobacillus actinomycetemcomitans was
      not detected in any of the 26 edentulous subjects. Porphyromonas gingivalis was
      detected in 2 subjects (proportion of cultivable flora: 0.002% and 12.5%).
      Prevotella intermedia was recovered from 7 subjects with a mean proportion of
      0.5% (range < 0.001%-6.3%). Analysis showed that subjects harbouring P.
      intermedia were wearing full dentures for a longer period of time (mean: 20.2
      years) than subjects in which P. intermedia could not be detected (mean: 6.6
      years). This result suggests that the absence of P. intermedia shortly after
      extraction may reflect only a temporary event. Other Prevotella species were
      found in 22 subjects, constituting < 2% of the total cultivable flora (range
      0.01%-10.5%). In conclusion, the low prevalence of P. gingivalis and the absence
      of A. actinomycetemcomitans, suggest that the oral cavity of edentulous subjects
      may not be regarded as a habitat for these species. The preferable habitat of the
      Prevotella spp. seems to be the oral mucous membranes, possibly with the
      exception of P. intermedia.

PMID- 8550863
TI  - Response to intracrevicular controlled delivery of 25% tetracycline from
      poly(lactide/glycolide) film strips in SPT patients.
AB  - Controlled local delivery of antibiotics has been shown to reduce
      periodontopathic micro-organisms with minimal side-effects. Clinical studies in
      our laboratory have shown that 25% tetracycline HCl delivered from poly(D,L
      lactide/glycolide) film strips (25 TTC-PLGA) released therapeutic concentrations
      of tetracycline for 10 days. The present pilot study compared the intracrevicular
      delivery of 25% tetracycline HCl incorporated in these biodegradable film strips
      to scaling and root planing (SRP) in 10 adult periodontitis patients, who in
      spite of therapy and regular supportive periodontal treatment (SPT), continued to
      possess 5 bleeding periodontal pockets at least 5 mm deep. Sites were randomly
      selected to receive the following treatments: (1) 25 TTC-PLGA, (2) control strips
      without TTC (PLGA), (3) SRP, and (4) untreated control. Film-strip retention was
      augmented with a suture/cement technique, followed by strip removal after 2
      weeks. Clinical parameters and subgingival bacterial morphotypes (darkfield
      analysis) were evaluated over time (0, 2.4, 8, 12, 26 weeks). Results indicated
      that, compared to baseline, 25 TTC-PLGA film strips caused significant (p < or =
      0.01): (1) probing depth reduction for 26 weeks, (2) a clinical attachment level
      gain for 12 weeks, (3) lower %s of spirochetes for 4 weeks and motile rods for 8
      weeks (p < or = 0.05), and (4) an accompanying increase in cocci for 4 weeks. In
      the scaled and root planed sites, probing depth was the only finding that
      demonstrated a significant change from baseline (p < or = 0.01). Controls and
      PLGA showed isolated reductions in probing depth and % of motile organisms. From
      these findings, applications of intracrevicular 25 TTC-PLGA, when compared to
      scaling and root planing, appears to have an enhanced antibacterial effect and a
      similar clinical effect in SPT patients. The results of this study indicate
      further investigation of 25 TTC-PLGA film strips should be undertaken using more
      subjects and sophisticated microbiological and clinical measurements.

PMID- 8550864
TI  - Removal of hard tooth structure by ROOTSHAPE root planing files used with a
      modified EVA contra-angle.
AB  - The results of numerous recent investigations indicate that root contamination
      with bacteria and endotoxins is limited to the root surface only. Therefore,
      methods on root surfaces instrumentation that preserve root substance should be
      focused on. Newly available instruments or treatment systems should be evaluated
      for their root substance-removing potential. The devices for root planing
      presented here comprised specific files (Rootshape) (with diamond-coating on
      their convex working surfaces used in conjunction with a water-spray-cooled
      contra-angle head transforming rotational movements into translatory
      oscillations. The substance-removal potential of rigid and flexible files with
      diamond coatings of 2-4, 15, 25 and 40 microns compared with that of regular hand
      curettes, was evaluated under various working forces. The results demonstrated,
      that depending on the grit size of the diamond coating, the Rootshape files
      removed less and in no instance greater amounts of root surface substance than
      did hand instruments.

PMID- 8550865
TI  - Clinical evaluation of natural coral and porous hydroxyapatite implants in
      periodontal bone lesions: results of a 1-year follow-up.
AB  - This study examines the suitability of 2 bone graft substitutes, natural coral
      skeleton (NCS) and porous hydroxyapatite (PHA) for treating periodontal bone
      defects in human subjects, and compares them to debridement alone (DEBR). A total
      of 30 sites in 10 patients were treated. Measurements were made before treatment
      and during surgical reexamination 12 months after treatment on lesions filled
      with NCS (10 sites), PHA (10 sites), or DEBR (10 sites). There was no significant
      difference in the use of NCS or PHA for 1, 2 wall, or combined defects for the
      group of parameters measured in this study (clinical probing depth, clinical
      attachment, gingival recession, bone fill, % bone fill, and crest remodelling).
      Statistical analysis (Wilcoxon non-parametric test for paired values and ANOVA
      for repeated measurements) revealed the beneficial effects of using each the
      biomaterials (57.4% for NCS, 58.1% for PHA, p < 0.86) as opposed to simple
      debridement (22.2%; p < 0.002; p < 0.004).

PMID- 8550866
TI  - The subgingival microflora and gingival crevicular fluid cytokines in refractory
      periodontitis.
AB  - Refractory periodontitis manifests as a rapid, unrelenting, progressive loss of
      attachment despite the type and frequency of therapy. This study examined
      possible relationships between cytokine levels in gingival crevicular fluid
      (GCF), occurrence of specific periodontopathic microflora, and disease activity
      in patients with refractory periodontitis. Refractory periodontitis patients (7
      male and 3 female) were selected on the basis of history and longitudinal
      clinical observations. In each patient, 2 teeth with pocket depths greater than 6
      mm were selected and individual acrylic stents were fabricated with reference
      grooves for each site. The sites were examined at both baseline and 3 months
      later. The pattern and amount of alveolar bone resorption were assayed by
      quantitative digital subtraction radiography. Pocket depth and attachment loss
      were measured with a Florida Probe. The gingival index was measured at 4 sites
      around each sample tooth. Sites were divided into active sites (> or = 2.1 mm
      loss of attachment in 3 months) or inactive sites (< or = 2.0 mm loss of
      attachment in 3 months). The distribution and prevalence of the predominant
      microflora in active and inactive sites were compared using anaerobic culture and
      indirect immunofluorescence. Interleukin-1 beta, 2, 4, 6 and tumor necrosis
      factor-alpha (TNF-alpha) levels in gingival crevicular fluid (GCF) were
      quantified by ELISA. Prevotella intermedia and Eikenella corrodens significantly
      decreased in inactive sites but remained the same in active sites after 3 months.
      The active sites revealed significantly higher GCF levels of IL-2 and IL-6 than
      inactive sites at both baseline and at 3 months. IL-1 beta was also significantly
      greater in active sites than in inactive sites at 3 months. Alveolar bone loss in
      active sites correlated with increased GCF levels of IL-1 beta and IL-2. These
      results suggest that GCF levels of IL-1 beta, IL-2 and IL-6 and P. intermedia and
      E. corrodens in subgingival plaque may serve as possible indicators of disease
      activity in refractory periodontitis.

PMID- 8550867
TI  - The prevalence of grandmothers as primary caregivers in a poor pediatric
      population.
AB  - In the wake of the HIV/AIDS and crack cocaine epidemics, poor urban communities
      face growing numbers of older adults, largely grandmothers, who have become
      surrogate parents to children orphaned by these epidemics. This study is the
      first in the United States to determine the prevalence of older surrogate parents
      among families registered at pediatric clinics. The three clinics selected were
      in low income neighborhoods of New York City with a high incidence of female
      HIV/AIDS and substance abuse. Using a 50% random sample of 1,375 records of
      registered families, data were obtained on the number and ages of relatives
      serving as surrogate parents. In 11% of these 1,375 families with children 12
      years and under a parent was not the caregiver. In 8% the caregiver was a
      grandmother. Forty-seven percent of these women were 55 years or older, 25% were
      60 years or older and 8% were 70 years or older. Most of these women were caring
      for more than one child. Ten percent of the total of 2,445 children, 12 years and
      under, lived in non-parent headed families. Eight percent lived with a
      grandmother, 1% with other parental generation relatives and 1% in foster care.
      Given the stresses associated with caregiving in late life and the greater risk
      of poor health among low income African-American and Hispanic elderly, older
      surrogate parents from these communities are a potentially high health risk
      population whose own needs may go unrecognized and unattended. The young ages of
      the children suggest that many grandparents may continue to be caregivers as they
      reach their sixties, seventies and even eighties. Clinical and longitudinal data
      are needed to determine how prolonged surrogate parenting in late life affects
      the health of older caregivers and the children in their care. Coordination
      between health and social services for the elderly and for children are needed to
      promote effective programs for these families.

PMID- 8550868
TI  - Herbal knowledge on Nicaragua's Atlantic Coast: consensus within diversity.
AB  - This article examines knowledge of medicinal plants, both among the people of
      Nicaragua's Atlantic Coast and among the scientific community. Data collected
      during an 809-household, five-community survey in 1990 and a ten-community
      botanical collection in 1991 are used to estimate the distribution of medicinal
      plant knowledge among the region's six ethnic groups. The list of 162 plants
      identified during this project is compared with other research results to provide
      the reader with a framework for understanding the distribution of medicinal plant
      knowledge. While a few plants are widely thought to have medicinal properties,
      the majority of identifications come from only one or two informants,
      demonstrating a pattern of consensus within diversity. Discussion focuses on the
      impact of methodology on the gathering of data, on the distribution and
      durability of medicinal plant knowledge, and on the proprietary nature of such
      knowledge.

PMID- 8550869
TI  - A comparison of health status between rural and urban adults.
AB  - The objective of the study was to examine and compare health status between rural
      and urban adults. The data are from a 1993 statewide probability-based telephone
      survey of adult Kentuckians (n = 662). Metropolitan Statistical Area (MSA)
      residents (n = 264) and nonMSA residents (n = 398) were compared using the
      Medical Outcomes Study, Short Form Health Survey (SF-20). Self-perceived urban (n
      = 406) and rural (n = 256) residents were also compared. Additional analyses were
      stratified by the age categories of 18-44, 45-64, and > or = 65 years of age. Few
      differences in health status existed between rural and urban adults. However,
      rural elders (> or = 65 years) had significantly poorer health status than urban
      elders. After controlling for demographic variables in multiple regressions,
      rural elders had significantly poorer functioning (all p < .05) than urban elders
      as measured by the SF-20 subscales of a) physical functioning, b) role
      functioning, c) social functioning, d) general mental health, and e) general
      health perceptions. No differences between rural and urban residents were noted
      for the pain subscale. Although the health status of rural and urban adults is
      generally similar, the rural elderly have significantly worse health status than
      their urban counterparts.

PMID- 8550870
TI  - The relationship of water sources and other determinants to prevalence of
      intestinal protozoal infections in a rural community of Saudi Arabia.
AB  - A study was carried out in a rural area of Asir region in Southwest of Saudi
      Arabia where information on the types of domestic water supply and
      sociodemography in relation to intestinal protozoal infections were obtained from
      1417 inhabitants (81.4% of the total) of nine villages. Stool samples were
      collected from the study population and examined for intestinal parasites.
      Overall, the prevalence rates of infection with the common water-borne parasites,
      Giardia lamblia and Entamoeba histolytica were 18.9% and 9.2% respectively, which
      were high compared to other endemic areas of the Kingdom. The sociodemographic
      factors including age, sex, degree of education, intrafamilial clustering and
      crowding index were found to be non significant determinants of both protozoal
      infections. The source of domestic water was the sole factor significantly
      associated with the high prevalence rates of infection in the community. This
      relationship was confirmed by multiple logistic regression analysis. A
      significantly high risk of contracting the infection with both parasites was
      observed among individuals who drank jar water (OR = 2.973, 95%CI:1.515-4.402 and
      OR = 2.831, 95%CI:1.414-3.915, for G. lamblia and E. histolytica respectively) or
      well water (OR = 2.153, 95%CI:1.211-3.913 and OR = 2.117, 95%CI:1.341-3.715, for
      G. lamblia and E. histolytica respectively). Those who used desalinated water for
      drinking seems to have the lowest degree of exposure to the risk of infection (OR
      = 0.689, 95%CI:0.501-0.849 and OR = 0.793, 95% CI:0.518-0.912, for G. lamblia and
      E. histolytica respectively). The results indicate that the use of improved water
      supply, including protection of community wells and domestic storage tanks,
      together with mandatory inspection measures during transportation and
      distribution of commercial water should reduce the rate of infection with the two
      protozoal parasites in this rural community.

PMID- 8550871
TI  - Where have all the autopsies gone? A proposal for a centralized autopsy service.
AB  - A litany of reasons have been advanced to account for the decrease in hospital
      autopsy rates. Increased attention has recently been centered on the difficulty
      hospital and medical examiner morgues are encountering in controlling infectious
      disease and attempting to comply with federal and state environmental regulatory
      agencies. The problem has been highlighted by autopsy examinations upon increased
      numbers of immuno-compromised patients harboring both the HIV and secondary drug
      resistant tuberculosis organisms. These developments occur at a time when there
      are budgetary restraints on hospitals and medical examiners' offices facing large
      expenditures involving morgue reconstruction to comply with ventilatory and
      infection control procedures mandated by state and federal agencies. Challenging,
      also, are the liability aspects, as patients and staff are potentially exposed to
      a variety of infectious agents. A possible solution is presented involving
      central off-hospital site facilities to which hospital autopsies can be funneled.
      A community morgue meeting the strict standards of infection control would allow
      economy of scale from daily use with a full time support staff trained in the
      protocol of infectious disease control.

PMID- 8550872
TI  - Morphology of thalamocortical neurons projecting to the primary somatosensory
      cortex and their relationship to spinothalamic terminals in the squirrel monkey.
AB  - This study examined the morphology of thalamocortical neurons projecting to the
      primary somatosensory cortex (SI; hand region of areas 3a, 3b, 1, and 2) and
      their relationship to the spinothalamic (STT) terminals in the squirrel monkey.
      Retrogradely labeled thalamocortical neurons were intracellularly filled with
      Lucifer yellow (LY), and the STT terminals were anterogradely labeled with
      biotinylated dextran. Both filled neurons and labeled terminals were
      differentially visualized in the same field by a dual immunocytochemical staining
      method. SI-projecting neurons appeared at the light level to be in contact with
      STT terminal boutons in the ventroposterior lateral (VPL), ventroposterior
      inferior (VPI), and centrolateral (CL) nuclei and the posterior complex (PO). The
      analyses of the neuronal morphology revealed that somatic and dendritic
      morphologies of SI-projecting neurons in these thalamic nuclei, as well as in the
      anterior pulvinlar (Pulo), centromedial (CM), and ventrolateral (VL) nuclei, were
      generally comparable with some exceptions: VL neurons had the largest soma sizes,
      the most primary dendrites, and the longest total dendritic length among all
      neurons studied; VPI neurons had the smallest soma sizes; VPL SI-projecting
      neurons were different from those in VPI in their soma sizes, shape factors, and
      orientations; in VPL the cells projecting to the superficial layers of SI were
      smaller than those projecting to the deeper layers, but in VPI the two groups of
      neurons were similar in soma sizes. In general, the SI-projecting neurons in VPL,
      VPI, and CL were similar in their dendritic morphologies and branching patterns,
      and varied from those in Pulo, PO, CM, and VL.

PMID- 8550873
TI  - Morphological diversity and glutamate immunoreactivity of retinal terminals in
      the suprachiasmatic nucleus of the cat.
AB  - Although the cat visual system has been the subject of intensive investigation,
      little attention has been given to the morphological features of ganglion cell
      projections to the suprachiasmatic nucleus. The present study has utilized
      anterograde transport of horseradish peroxidase and wheat germ agglutinin
      conjugated horseradish peroxidase to label ganglion cell terminals in the cat
      suprachiasmatic nucleus. Visualization of the reaction product was facilitated
      through the use of gold-substituted silver intensification. Ganglion cell
      terminals were found to be morphologically diverse, making both asymmetric and
      symmetric contacts with postsynaptic processes. Synaptic vesicles were either
      scattered or densely packed, sometimes forming paracrystalline arrays. In
      contrast to other retinorecipient areas in which ganglion cell terminals have
      been characterized by the presence of lightly staining mitochondria, many of the
      retinal terminals in the suprachiasmatic nucleus were seen to contain darkly
      stained mitochondria. Postembedding antiglutamate immunocytochemistry was used to
      evaluate the level of endogenous glutamate in these ganglion cell terminals.
      Although morphologically diverse, all of the retinal terminals in the
      suprachiasmatic nucleus were glutamate positive, consistent with the postulated
      role of glutamate as the neurotransmitter of retinal ganglion cells.

PMID- 8550874
TI  - Two rules for callosal connectivity in striate cortex of the rat.
AB  - In the rat, callosal cells occupy lateral as well as medial portions of striate
      cortex. In the region of the border between areas 17 and 18, which contains a
      representation of the vertical meridian of the visual field, cells projecting
      through the corpus callosum are concentrated throughout the depth of the cortex.
      In contrast, in medial portion of striate cortex, where peripheral portions of
      the visual field are represented, callosal cells are preferentially found in
      infragranular layers. These differences in topography and laminar distribution
      suggest that these callosal regions, referred to as medial and lateral callosal
      regions in the present study, subserve different functions. We explored this
      possibility by analyzing the patterns of callosal linkages in these two callosal
      regions. We charted the location of retrogradely labeled cells within striate
      cortex of one hemisphere after placing restricted injections of one or more
      fluorescent tracers into selected sites in the contralateral striate cortex. We
      found the medial and lateral callosal regions have distinctly different
      topographic organizations. Injections into medial striate cortex of one
      hemisphere produced labeled cells predominantly in mirror-symmetric loci in
      medial portions of contralateral striate cortex. The arrangement of these
      connections suggests that they mediate direct interactions between cortical
      regions representing visual fields located symmetrically on opposite sides of the
      vertical meridian of the visual field. In contrast, the mapping in the lateral
      callosal region is reversed: injections into the 17/18a border produced labeled
      fields located medial to the contralateral 17/18a border, while injections
      slightly medial to the 17/18a border produced labeled fields located at the
      contralateral 17/18a border.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8550875
TI  - Effects of neonatal enucleation on the organization of callosal linkages in
      striate cortex of the rat.
AB  - Lewis and Olavarria ([1995] J. Comp. Neurol. 361:119-137) showed that the
      mediolateral organization of callosal linkages differs markedly between medial
      and lateral regions of striate cortex in the rat. Thus, callosal fibers
      originating from medial regions of striate cortex interconnect loci that are
      mirror-symmetric with respect to the midsagittal plane. In contrast, fibers from
      lateral regions of striate cortex show a reversed pattern of connections: tracer
      injections into the 17/18a border produce retrograde cell labeling in regions
      medial to the contralateral 17/18a border, whereas injections placed somewhat
      medial to the 17/18a border label cells located at the contralateral 17/18a
      border. Based on the interpretation that callosal fibers from lateral striate
      cortex connect retinotopically corresponding loci (Lewis and Olavarria [1995] J.
      Comp. Neurol. 361:119-137) we propose here that the development of the reversed
      pattern of connections in lateral portions of striate cortex is guided by
      activity-dependent cues originating from spontaneously active ganglion cells in
      temporal retina. In the present study we have attempted to falsify this
      hypothesis by investigating the effects of neonatal bilateral enucleation on the
      organization of callosal linkages in striate cortex of the rat. Once enucleated
      rats reached adulthood, we studied the mediolateral organization of callosal
      connections by placing small injections of different fluorescent tracers into
      different loci within medial and lateral striate cortex. The analysis of the
      distribution of retrogradely labeled callosal cells indicated that connections
      from lateral portions of striate cortex were no longer organized in a reversed
      fashion, rather, they resembled the mirror image pattern normally found in the
      medial callosal region, i.e., injections at the 17/18a border produced labeled
      cells at the opposite 17/18a border, whereas injections into slightly more medial
      regions produced labeled cells in the opposite, mirror-symmetric location. In
      addition, we found that enucleation does not alter the organization of callosal
      linkages in medial portions of striate cortex. Thus, by showing that enucleation
      significantly changes the pattern of connections from lateral portions of striate
      cortex, the present study does not falsify, but rather strengthens the hypothesis
      that interhemispheric correlated activity driven from the temporal retinal
      crescent guides the normal development of reversed callosal linkages in lateral
      portions of rat striate cortex. Furthermore, the present study shows that, in the
      absence of the eyes, the pattern of callosal linkages in lateral portions of
      striate cortex resembles the mirror image pattern normally found only in medial
      striate cortex.

PMID- 8550876
TI  - Development of neuropeptide Y immunoreactive amacrine and ganglion cells in the
      pre- and postnatal cat retina.
AB  - In the adult cat, neuropeptide Y (NPY) immunoreactivity (IR) is found within a
      subgroup of gamma-type ganglion cells and a large group of regularly arrayed
      amacrine cells. To examine the development of these two cell groups, we charted
      the appearance and maturation of neuropeptide Y immunoreactivity in the pre- and
      post-natal cat retina. Neuropeptide Y immunoreactivity is first observed at the
      central retina within the ganglion cell layer on embryonic day 46, and
      immunoreactivity within amacrine cells of the inner plexiform layer is present by
      E50. The number of immunoreactive profiles reaches the adult level in the
      amacrine population first (around P7), while the ganglion cell population shows a
      protracted development, with new cells being added until the third postnatal
      week. NPY-immunoreactive profiles in the ganglion cell layer were confirmed to be
      ganglion cells by retrograde labeling in both pre- and post-natal animals. Thus,
      neuropeptide Y-immunoreactive ganglion cells and amacrine cells attain their
      mature state with very different timecourses, although both cell groups initially
      follow a central to peripheral pattern of development. Interestingly, NPY
      expression within the ganglion cell population is temporally correlated with
      retinal synaptogenesis in the inner plexiform layer. As in the adult cat, NPY
      immunoreactive ganglion cells never show a regular distribution during
      development, while NPY-IR amacrine cells are always distributed regularly even at
      the earliest ages. The prenatal presence of a regular distribution of NPY-IR
      amacrine cells suggests that these cells may participate in establishing the
      ganglion cell mosaics that appear during postnatal development.

PMID- 8550877
TI  - Central projections of the antennal cold receptor neurons and hygroreceptor
      neurons of the cockroach Periplaneta americana.
AB  - The central projections of the cold receptor axons were examined by filling two
      types of cold receptive sensilla with cobalt lysine--a cold and hygroreceptive
      (C/H) sensillum and a cold receptive and olfactory (C/O) sensillum--on the
      antennae of the cockroach, Periplaneta americana L. When the dye filled a single
      C/H sensillum, four axons were stained. Three of these axons terminate in the
      ipsilateral antennal lobe, while the other branches in the ipsilateral dorsal
      lobe. One of the branches passed through the tritocerebrum to terminate in the
      suboesophageal ganglion, while the other branches end in the lobe. When a single
      C/O sensillum is dye filled, all axons of the four receptor neurons terminate
      exclusively in the ipsilateral antennal lobe. One axon from the C/H sensillum and
      one axon from the C/O sensillum terminate in a particular glomerulus in the
      ventroposterior region of the antennal lobe. Each of these axons also has a tuft
      in separate glomeruli situated just dorsal to the glomerulus in which both axons
      terminate. This set of three glomeruli have indistinct boundaries and appear to
      form a complex of glomeruli similar to the macroglomerular complex of male moths.
      Assuming modality-specific convergence of antennal afferents, these axons appear
      to belong to the cold receptor neurons, and the set of glomeruli appear to
      function in cold reception. Two other neurons stained from C/H sensilla always
      terminate in the glom-eruli distinct from the set of glomeruli mentioned earlier.
      These neurons are assigned to the pair of hygroreceptor neurons, and their
      glomeruli are thought to function in hygroreception.

PMID- 8550878
TI  - Development of calretinin immunoreactivity in the neocortex of the rat.
AB  - The prenatal and postnatal development of calretinin (CR)-containing elements in
      the neocortex of the rat was analyzed using immunohistochemistry. CR
      immunoreactivity in the cortical anlage appeared early at embryonic day 14 (E14),
      with CR-positive neurons located in the primitive plexiform layer and in the
      emerging subplate and marginal zones. At later prenatal and early postnatal
      stages, these two layers showed the highest CR immunostaining in the cortex, and
      large numbers of cell bodies and fibers were immunostained. From postnatal day 3
      (P3) onwards, CR immunostaining disappeared progressively from the subplate-layer
      VIb and the marginal zone-layer I, so that very few cells remained stained in
      these layers in the adult. In the cortical plate and prospective layers VIa to II
      III, CR-positive neurons were seen at prenatal stages, their numbers increasing
      markedly during the first postnatal week. Most neurons showed undifferentiated
      nonpyramidal shapes, and matured during the second and third postnatal weeks,
      when the adult pattern of CR immunostaining was achieved. In addition, some
      pyramidal-like neurons in the infragranular layers and in layer II-III
      transiently expressed CR during the postnatal period, most notably between P3 and
      P12. Colocalization experiments performed at P0-P3 with antibodies against the
      neurotransmitter gamma-aminobutyric acid (GABA) showed that most nonpyramidal CR
      positive neurons in the derivates of the cortical plate were also GABAergic
      during development. In contrast, large numbers of CR-containing neurons in the
      subplate and marginal zone were GABA-negative. The present results show that in
      addition to recording the early development of a subset of nonpyramidal neurons,
      CR is transiently expressed in certain GABA-negative populations of the subplate
      and marginal zone, and most likely in pyramidal neurons.

PMID- 8550879
TI  - Immunocytochemical study of choline acetyltransferase in Drosophila melanogaster:
      an analysis of cis-regulatory regions controlling expression in the brain of cDNA
      transformed flies.
AB  - We have analyzed the cis-regulatory regions in the 5' flanking DNA of the
      Drosophila melanogaster choline acetyltransferase (ChAT; E.C. 2.3.1.6) gene by
      using germline transformants. These transformants are carrying wild-type ChAT
      cDNA fused to different lengths of 5' flanking sequence of the ChAT gene.
      Appropriate genetic crosses were used to introduce the transgene into animals
      with a presumptive null genetic background for endogenous ChAT. Expression of
      ChAT protein could thus be attributed exclusively to the transgene. Using a
      monoclonal antibody against Drosophila ChAT, we have investigated the spatial
      distribution of transgenic ChAT and compared it to the normal distribution of
      ChAT protein in wild-type animals. The brains of 7.4 kb cDNA transformants showed
      a ChAT expression pattern similar to that of wild-type animals in the first- and
      second-order sensory neuropil but reduced expression in other highly ordered
      neuropil. Several lines that were transformed with 1.2 kb or 0.8 kb of 5'
      flanking DNA demonstrated relatively normal expression in sensory neuropil. In
      addition, these lines also showed ectopic expression in higher order neuropil. In
      the optic lobe, the expression pattern directed by 7.4 kb of 5' flanking DNA was
      very similar to that of wild-type ChAT expression. In contrast, 1.2 kb or 0.8 kb
      transformants showed reduced levels of expression and a more limited pattern of
      distribution in the optic lobe. Our results suggest that the 5' flanking DNA of
      the ChAT gene can be divided into several separable positive and negative
      regulatory regions, which define various subsets of cholinergic neurons in the
      nervous system.

PMID- 8550880
TI  - Anatomical basis for interactions of enkephalins with other transmitters in the
      CNS of a snail.
AB  - Immunocytochemical techniques for double staining were employed to investigate
      the morphological basis for interactions between enkephalins and other
      neuroactive compounds in the behavior of the gastropod mollusc Cepaea nemoralis.
      Coexistence of each of the two enkephalins with FMRFamide, serotonin or GABA-like
      immunoreactivity was found in certain neurons in cerebral, parietal, and pedal
      ganglia. Tyrosine hydroxylase-immunoreactive neurons were occasionally seen in
      close apposition to, but never colocalized with, the enkephalins. A comparison
      between these anatomical observations and previous behavioral studies suggests
      that in gastropod molluscs cotransmission of enkephalins with classical
      transmitters may, at least partly, reflect synergism of these substances in the
      control of definite behavioral programs.

PMID- 8550881
TI  - Vasopressin and galanin mRNAs coexist in the nucleus of the horizontal diagonal
      band: a novel site of vasopressin gene expression.
AB  - Vasopressin (VP) neurons have been identified in several brain regions where VP
      has been hypothesized to act as a neurotransmitter or neuromodulator. In many
      sites, VP is colocalized with the neuropeptide galanin (GAL). Here, using single
      in situ hybridization histochemistry, we have identified a novel group of neurons
      within the nucleus of the horizontal diagonal band of Broca (HDB) that express
      the VP gene and have assessed the distribution of these cells in adult male and
      female rats (90 days old, n = 7/group). VP mRNA-expressing neurons were scattered
      throughout the rostrocaudal extent of the HDB, and the number of VP neurons
      detected unilaterally ranged from 1 to 17 cells per 20 microns section. Using
      double in situ hybridization histochemistry on alternate sections, we have
      assessed the number of cells expressing VP and/or GAL mRNA in the diagonal band
      and have determined the extent of their colocalization. Approximately 50% of all
      VP-expressing neurons in the HDB coexpressed GAL mRNA, and 33% of GAL-expressing
      neurons in this region coexpressed VP mRNA. No sex differences were detected in
      the number of neurons expressing either VP or GAL mRNA or in the incidence of
      coexpression of VP and GAL mRNAs in this region. VP neurons in the HDB exhibited
      a low level of expression, and cellular VP mRNA content did not differ between
      male and female rats. However, sex differences were present in the bed nucleus of
      the stria terminalis (BNST) of these same rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8550882
TI  - Dopamine receptor mRNA expression patterns by opioid peptide cells in the nucleus
      accumbens of the rat: a double in situ hybridization study.
AB  - Colocalization of proenkephalin and prodynorphin mRNAs with each other as well as
      with D1, D2, and D3 dopamine receptor mRNAs was analyzed in the nucleus accumbens
      of the rat. Distinct combinations were detected in the rostral pole, core, and
      shell subdivisions of the nucleus accumbens. Proenkephalin and prodynorphin mRNAs
      were principally localized in separate cells in the core. All detectable
      prodynorphin cells in the core expressed D1 mRNA but not D2 mRNA. Conversely,
      approximately 95% of the proenkephalin-positive cells in this region expressed D2
      mRNA but not D1 mRNA. This pattern was identical to that observed in the caudate
      putamen. In the rostral pole and the shell, embedded in a background of this
      "typical" colocalization pattern, clusters of cells expressing a distinct
      configuration were found. In these clusters, proenkephalin-positive cells
      expressed both prodynorphin and D1 mRNAs, but they did not express D2 mRNA. D3
      and prodynorphin mRNAs were colocalized in "limbic" striatal areas, including the
      ventromedial caudate putamen, the rostral pole, and the medial shell. In
      contrast, D3 mRNA was not detected in any proenkephalin-positive cells. Together
      with the prodynorphin/D1 data, this suggests that a subset of prodynorphin cells
      expresses both D1 and D3 mRNAs. It is concluded that 1) clusters of cells that
      coexpress proenkephalin, prodynorphin, and D1 mRNAs overlap extensively with
      previously defined cytoarchitectural cell clusters in the nucleus accumbens and
      2) a subset of the prodynorphin cells in the ventromedial caudate putamen and the
      nucleus accumbens contains both D1 and D3 mRNAs.

PMID- 8550883
TI  - Topographical organization in the early postnatal corticopontine projection: a
      carbocyanine dye and 3-D computer reconstruction study in the rat.
AB  - We have explored basic rules guiding the early development of topographically
      organized projections, employing the rat corticopontine projection as a model
      system. Using anterograde in vivo tracing with 1,1',dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate (DiI), we studied the distribution of
      labelled fibers in the pontine nuclei in relation to cortical site of origin
      during the first postnatal week. Labelled corticopontine fibers enter the pontine
      nuclei in distinct, sharply defined zones. The putative terminal fibers typically
      occupy lamella-like subspaces. Related to changes in cortical site of origin, we
      describe mediolateral, internal to external, and caudorostral distribution
      gradients in the pontine nuclei. Fibers originating in the anterolateral cortex
      occupy an internal central core, while implantations at increasing distance from
      the anterolateral cortex produce 1) more externally located lamellae, and 2) a
      caudal to rostral shift in fiber location. Previous investigations have shown
      that pontocerebellar neurons migrate into the ventral pons in a temporal sequence
      (Altman and Bayer [1987] J. Comp. Neurol. 257:529). The earliest arriving neurons
      occupy the central core and later arriving neurons settle in more externally and
      rostrally located subspaces. We hypothesize that the earliest arriving
      corticopontine fibers grow into the then only available zone of pontocerebellar
      neurons (central core), attracted by a diffusible chemotropic cue. Later arriving
      fibers grow into correspondingly later and more externally and rostrally located
      contingents of pontocerebellar neurons. Thus, we propose that the topographical
      organization in the early postnatal corticopontine projection is determined by
      simple temporal and spatial gradients operative within source (cerebral cortex)
      and target region (pontine nuclei).

PMID- 8550884
TI  - Periventricular morphology in the diencephalon of antarctic notothenioid
      teleosts.
AB  - We have examined the subependymal region of the diencephalic third ventricle in
      notothenioid perciforms and report a pattern of neuropil expansions that appears
      to be phyletically derived for notothenioids and their outgroups but that is
      otherwise unique among vertebrates. We recognize five types of expansions based
      on their composition (from less dense neuropil to sacs) and width or protrusion
      into the third ventricle. In the species with the most elaborate morphology,
      Trematomus bernacchii, bilateral subependymal expansions fuse along the midline
      to form a single sac within the ventricular cavity. The extent of these
      expansions loosely corresponds with phyletic position but also (and perhaps more
      importantly) is correlated with the habitation of cold water (r2 = 0.48; P =
      0.012). Furthermore, subependymal expansion type is positively correlated with
      the maximum size of the soma of neurons in two hypothalamic nuclei, the
      preopticus magnocellularis (r2 = 0.54; P = 0.006) and the lateralis tuberis (r2 =
      0.40; P = 0.038). These nuclei project to the pituitary and contain cerebrospinal
      fluid-contacting neurons. In considering the functional consequences of this
      morphology, we cannot dismiss the possibility that these structures form a
      specialized enteroceptive system tied to the monitoring of cerebrospinal and
      extracellular fluid components, including antifreeze glycopeptides and inorganic
      ions.

PMID- 8550885
TI  - Use and abuse of fractal theory in neuroscience.

PMID- 8550886
TI  - Distribution of non-NMDA glutamate receptor mRNAs in the developing rat cochlea.
AB  - In situ hybridization was used to document the distribution of mRNA encoding six
      subunit isoforms of non-N-methyl D-aspartic acid (NMDA) glutamate receptors
      (GluR1, GluR2, GluR3, GluR4, GluR5 and GluR6) in the inner ears of embryonic,
      postnatal and adult rats. GluR2 and GluR3 expression in the spiral ganglion
      appeared well before birth, and reached adult levels several days before the
      onset of function in the cochlea. In the spiral limbus, expression of GluR2 and
      GluR3 mRNA reached very high levels at around the time of birth, then declined
      after a few days. Low levels of GluR1, GluR4 and GluR6 expression were detected
      in various tissues of the cochlea during development. In the adult cochlea, GluR
      expression was limited to GluR2 and GluR3 mRNAs in the spiral ganglion neurons
      and GluR2 mRNA in fibrocytes of the spiral limbus, a non-neural tissue. The
      ontogenetic expression of additional GluR subunit genes and their appearance in
      different cochlear tissues could reflect different roles for these genes during
      development, or less precise regulation of gene expression within the GluR
      family. In particular, the very high levels of GluR gene expression in the spiral
      limbus during the perinatal period support a non-neural function, perhaps as cell
      surface receptors during tissue differentiation.

PMID- 8550887
TI  - Patterns of convergence and segregation in the medial nucleus accumbens of the
      rat: relationships of prefrontal cortical, midline thalamic, and basal amygdaloid
      afferents.
AB  - In the rat, fibers from the prelimbic cortex terminate in the medial nucleus
      accumbens. Anterior paraventricular thalamic and parvicellular basal amygdaloid
      fibers reached both the prelimbic cortex and the medial nucleus accumbens. All
      three afferent systems have an inhomogenous distribution within the nucleus
      accumbens, and whether or not these projections actually reach the same areas is
      unknown. Our aim was to evaluate the relationships of the three afferents with
      respect to the shell, the core, and the cell clusters of the nucleus accumbens.
      Double anterograde tracing and single anterograde tracing combined with
      immunohistochemistry for calbindin (D28k) or Nissl stain was used. Following
      tracer injections in the prelimbic cortex and the anterior paraventricular
      thalamus, a complementary (i.e., nonoverlapping) pattern of fibers was found in
      the shell. Thus, afferents from the prelimbic cortex are associated with cell
      clusters, whereas those from the anterior paraventricular thalamus avoid these
      cells but are affiliated with regions exhibiting weak homogeneous calbindin
      immunoreactivity. In the calbindin-poor patches of the core, the situation is
      reversed as both sets of fibers overlap. In cases with injections in the
      prelimbic cortex and the parvicellular basal amygdala, a pattern of overlap was
      seen in the shell and core. Thus, the fibers in the shell were found together in
      association with cell clusters, whereas regions of weak homogeneous calbindin
      immunoreactivity were avoided. In the core, overlap was seen in the patch
      compartment. Finally, with parvicellular basal amygdala/paraventricular thalamus
      injections, a complementary fiber organization was present in the shell, but
      overlap was prominent in the patches of the core. The results demonstrate that
      the relationships of prelimbic cortical, paraventricular thalamic, and
      parvicellular basal amygdaloid afferents in the nucleus accumbens vary according
      to their compartmental (immunohistochemical and cellular) affiliation.
      Compartmentalization is therefore a possible anatomical substrate for
      condensation or segregation of neuronal signals passing through the nucleus
      accumbens.

PMID- 8550888
TI  - Presence or absence of TrkA protein distinguishes subsets of small sensory
      neurons with unique cytochemical characteristics and dorsal horn projections.
AB  - Investigations into the biological actions of nerve growth factor (NGF) have
      shown that dorsal root ganglion (DRG) neurons subserving nociception require NGF
      for survival and maintenance of phenotype. This discovery suggests that the
      signaling NGF receptor, TrkA, can be used as a marker for nociceptive neurons. In
      this study, we have used antibodies to TrkA, in conjunction with cell biological
      markers that show a restricted distribution in the DRG, to further characterize
      subsets of DRG neurons that are dependent upon NGF. Staining for TrkA labeled
      small and medium-sized neurons that composed 47% of all neurons in thoracic
      ganglia. Double-labeling with antibodies to the high molecular weight
      neurofilament protein (NFH), a marker for neurons with myelinated axons,
      demonstrated that TrkA staining is found in only a small subset of myelinated
      neurons. Surprisingly, many DRG neurons were not labeled by either TrkA or NFH.
      These neurons had small soma areas, contained the intermediate filament protein
      peripherin, and were labeled by the lectin BSI, identifying them as neurons
      likely to have unmyelinated axons. In addition, small TrkA-negative neurons were
      extensively labeled by antibodies to the intermediate filament protein alpha
      internexin, the delta isoform of protein kinase C, and by the BSI isolectin BSI
      B4. In order to assess the potential functions of TrkA-negative small neurons, we
      examined their projections to the dorsal horn of the spinal cord. TrkA
      immunoreactivity in the spinal cord was restricted to lamina I and the outer
      region of lamina II (IIo), similar to staining for calcitonin gene-related
      peptide. In contrast, the central projections of TrkA-negative neurons, as
      visualized by BSI-B4 staining, were particularly dense in lamina IIi. Our results
      suggest that TrkA-expressing and non-TrkA-expressing small neurons compose
      functionally distinct populations of DRG neurons.

PMID- 8550889
TI  - Glutamatergic and GABAergic input to rat spinothalamic tract cells in the
      superficial dorsal horn.
AB  - The distribution of synaptic terminals onto spinothalamic tract cells (types I
      and II) of the superficial dorsal horn was determined with special reference to
      the amino acid transmitters glutamate and gamma-aminobutyric acid. Fifteen
      spinothalamic cells retrogradely labeled from the thalamus with the
      neuroanatomical tracer wheatgerm agglutinin conjugated to horseradish peroxidase
      were sectioned for electron microscopy. Serial sections from several levels
      through each cell were immunostained for glutamate and gamma-aminobutyric acid
      using a postembedding immunogold technique. Perimeter measurements of
      spinothalamic cell somata and dendrites and the lengths of apposition for all
      terminal profiles in contact with the spinothalamic cells were obtained from
      electron micrographs using a digitizing tablet. These data were used to determine
      the density of terminals on the soma and dendrites. In addition, the terminal
      population on these cells was categorized by transmitter content (glutamate,
      gamma-aminobutyric acid, or unlabeled). The results demonstrate that terminal
      density increased on dendrites relative to their distance from the soma.
      Glutamatergic and GABAergic input composed 37% and 20% of the terminal
      population, respectively, and these percentages remained uniform for the soma and
      dendrites. There were no significant differences among the 15 cells analyzed for
      this study. The results, therefore, suggest that both type I and type II STT
      cells of the superficial DH have similar synaptic organizations.

PMID- 8550890
TI  - Morphogenetic reorganization of the brain during embryogenesis in the
      grasshopper.
AB  - We have studied the morphogenetic reorganization that occurs in the grasshopper
      brain during embryogenesis. We find that morphogenetic movements occur at three
      organizational levels during brain development. First, the entire developing
      brain changes its orientation with respect to the segmental chain of ventral
      ganglia. A 90 degrees shift in the attitude of the brain neuraxis occurs during
      embryogenesis due to a gradual upward movement of the cerebral structures in the
      head. Second, the clusters of proliferating neuroblasts and progeny that generate
      the neuroarchitecture of the mature brain move relative to one another and to
      nonneural structures such as the stomodeum. This is especially pronounced for the
      pars intercerebralis and for the tritocerebrum, as shown by annulin and engrailed
      immunoreactivity. Third, individual neuroblasts within a given proliferative
      cluster undergo positional reorganization during embryogenesis. Identified
      neuroblasts of the tritocerebrum and the pars intercerebralis are displaced
      within the brain. We conclude that the transformation of the simple sheet-like
      structure of the early embryonic brain into the highly differentiated structure
      of the mature brain involves a series of morphogenetic movements that occur in
      virtually all parts of the brain.

PMID- 8550891
TI  - "Satellite cells" and nerve terminals in the crayfish opener muscle visualized
      with fluorescent dyes.
AB  - Nerve terminals and associated cells on the muscle's surface were visualized in
      the crayfish opener muscle with several fluorescent dyes in conjunction with
      confocal microscopy and conventional fluorescence microscopy. The nerve terminals
      of the excitatory and inhibitory axons were best seen with 4-diethylaminostyryl-N
      methylpyridinium iodide (4-Di-2-Asp). This dye is selectively accumulated in
      mitochondria, which are numerous both in the axons and in synapse-bearing
      terminal varicosities. Muscle nuclei were also clearly visualized, because they
      excluded 4-Di-2-Asp but were stained by acridine orange (AO). A positive
      attraction between muscle nuclei and nerve terminals was evident by visual
      inspection and was confirmed by spatial statistics. Additional flat cells on the
      muscle's surface appeared as bright rings with elongated processes that were
      often close to or overlapped nearby nerve terminals. The structure of these cells
      was established by electron microscopy after labeling them with fluorescent
      polystyrene beads, which could be found over structures on the muscle surface in
      sections of embedded specimens. The flat surface cells were distinct from
      peripheral glial cells closely associated with axons and nerve terminals.
      Nevertheless, spatial statistics showed that the surface cells were grouped near
      nerve terminals. They occupied a small fraction of the muscle cell's surface.
      Their functional role has not been determined in crustacean muscles.

PMID- 8550892
TI  - Plasticity of mature sensory cerebrovascular axons following intracranial
      infusion of nerve growth factor.
AB  - Mature perivascular sympathetic axons associated with the intradural segment of
      the internal carotid artery (ICA) of the adult rat respond by sprouting following
      a two week infusion of nerve growth factor (NGF) into the lateral ventricle of
      the brain. Because nonsympathetic axons such as those comprising the sensory and
      parasympathetic population have been shown to respond to NGF, the present study
      was carried out to determine whether mature sensory axons respond to in vivo NGF
      infusion and whether competitive interactions between the innervating populations
      might affect the responsiveness of these axons to NGF. Standard electron
      microscopic techniques as well as calcitonin-gene-related peptide (CGRP)
      immunohistochemistry at the light microscopic level were used to examine the
      effects of intracerebroventricular NGF infusion on mature perivascular fibers
      with and without prior sympathetic denervation (i.e., bilateral superior cervical
      ganglionectomy). Following NGF infusion, CGRP-immunoreactive fibers appeared
      thicker and more numerous in the longitudinal plane when compared with vehicle
      controls. However, at the ultrastructural level, a significant increase in the
      total number of axons was not observed, although there was an increase in the
      number of large granular vesicles, suggesting that the CGRP fibers responded to
      exogenous NGF with an increase in neurotransmitter content, but not by sprouting.
      Sympathetic denervation, on the other hand, resulted in a significant increase in
      the number of fibers passing in the circumferential plane. The most dramatic
      change in CGRP immunoreactivity was observed following combined sympathetic
      denervation and subsequent NGF infusion, where, in addition to the presence of
      thicker immunoreactive fibers, a significant increase in the perivascular density
      of immunoreactive fibers associated with the intradural blood vessels was
      observed. These findings suggest that exogenous NGF has different effects on
      mature sympathetic and nonsympathetic fibers that innervate intradural blood
      vessels. The former exhibit robust sprouting, whereas the latter do not sprout in
      response to NGF but show evidence for increased neuropeptide content. In
      addition, the heightened response by sensory axons following denervation and
      subsequent NGF infusion provides support for the idea that sensory and
      sympathetic axons normally compete for target space and/or target-derived
      neurotrophic factors.

PMID- 8550893
TI  - Immunocytochemical identification of cone bipolar cells in the rat retina.
AB  - We studied the morphology of bipolar cells in fixed vertical tissue sections of
      the rat retina by injecting the cells with Lucifer Yellow and neurobiotin. In
      addition to the rod bipolar cell, nine different putative cone bipolar cell types
      were distinguished according to the position of their somata in the inner nuclear
      layer and the branching pattern and stratification level of their axon terminals
      in the inner plexiform layer. Some of these bipolar cell populations were labeled
      immunocytochemically in vertical and horizontal sections using antibodies against
      the calcium-binding protein recoverin, the glutamate transporter GLT-1, the alpha
      isoform of the protein kinase C, and the Purkinje cell marker L7. These
      immunocytochemically labeled cell types were characterized in terms of cell
      density and distribution. We found that rod bipolar cells and GLT-1-positive cone
      bipolar cells occur at higher densities in a small region located in the upper
      central retina. This area probably corresponds to the central area, which is the
      region of highest ganglion cell density. A second peak of rod bipolar cell
      density in the lower temporal periphery matches the retinal area of binocular
      overlap. The population densities of the immunocytochemically characterized
      bipolar cells indicate that at least 50% of all bipolar cells are cone bipolar
      cells. The variety and total number of cone bipolar cells is surprising because
      the retina of the rat contains 99% rods. Our findings suggest that cone bipolar
      cells may play a more important role in the visual system of the rat than
      previously thought.

PMID- 8550894
TI  - Retinal neurons and vessels are not fractal but space-filling.
AB  - Many branched patterns in nature are hypothesized to be fractal, i.e.,
      statistically self-similar across a range of scales. We tested this hypothesis on
      the two-dimensional arbors of retinal neurons and blood vessels. First, we
      measured fractalness on synthetic fractal and nonfractal patterns. The synthetic
      fractal patterns exhibited self-similarity over a decade of scale, but the
      nonfractal "controls" showed hardly any self-similarity. Neuronal and vascular
      patterns showed no greater self-similarity than the controls. Second, we
      manipulated a synthetic fractal pattern to remove its self-similarity and found
      this to be reflected in a loss of measured fractalness. The same manipulation of
      the nonfractal control and also of the neural and vascular patterns did not alter
      their measured fractalness. Third, we "grew" patterns of branched line segments
      according to a variety of nonfractal algorithms. These patterns were, if anything
      slightly more fractal than the neural and vascular patterns. We conclude that the
      biological patterns studied here are not fractal. Finally, we measured extended
      versions of these patterns: a contiguous array of homotypic neuron arbors and a
      vascular pattern with a high degree of total detail. These patterns showed a
      "fractal dimension" of 2, which implies that down to some cut-off scale they fill
      space completely. Thus, neural and vascular patterns might best be described as
      quasi-regular lattices.

PMID- 8550895
TI  - The glutamate-enriched cortical and thalamic input to neurons in the subthalamic
      nucleus of the rat: convergence with GABA-positive terminals.
AB  - Neurons of the subthalamic nucleus play a key role in the normal physiology and
      the pathophysiology of the basal ganglia. In order to understand better how the
      activity of subthalamic neurons and hence the output of the basal ganglia are
      controlled, we have reexamined the topography and examined in detail the
      synaptology and neurochemical nature of the two major excitatory projections to
      the subthalamic nucleus, that from the cortex and from the parafascicular nucleus
      of the thalamus. The approach was to use anterograde neuronal tracing and
      postembedding immunocytochemistry for amino acid transmitters. In confirmation of
      previous findings the cortical and thalamic projections were topographically
      organized, although the topography was more finely organized, and the projections
      more extensive, than previously demonstrated. Cortical and thalamic terminals
      made asymmetrical synaptic contacts with the dendrites and spines of subthalamic
      neurons. The thalamic terminals contacted larger postsynaptic targets, and
      therefore presumably more proximal regions of subthalamic neurons, than did the
      cortical terminals. Quantitative analysis of the postembedding immunolabelled
      sections revealed that the cortical and thalamic terminals were significantly
      enriched in glutamate-immunoreactivity when compared to identified gamma
      aminobutyric acid (GABA)-positive terminals, supporting physiological studies
      that suggest that these projections use glutamate as their neurotransmitter. In
      addition a small population of nonanterogradely labelled terminals that formed
      asymmetrical synapses and were immunopositive for GABA were identified. A larger
      population of terminals that formed symmetrical synapses were also immunopositive
      for GABA and were probably derived from the globus pallidus. The latter type of
      terminal was found to make convergent synaptic input with cortical or thalamic
      terminals on the dendrites and spines of subthalamic neurons, indicating that the
      "indirect pathways" by which information flows through the basal ganglia converge
      at the level of individual neurons in the subthalamic nucleus.

PMID- 8550896
TI  - Inositol 1,4,5-trisphosphate receptor localization in the brain of a weakly
      electric fish (Apteronotus leptorhynchus) with emphasis on the electrosensory
      system.
AB  - Inositol 1,4,5-trisphosphate is a widespread intracellular second messenger that
      mobilizes intracellular Ca2+ stores. The inositol 1,4,5-trisphosphate receptor
      involved is associated with the endoplasmic reticulum in neurons. In mammalian
      brain, inositol 1,4,5-trisphosphate receptor-containing neurons are found in many
      diverse regions, with cerebellar Purkinje cells containing the highest density of
      these receptors. We used immunohistochemical methods to identify the distribution
      of inositol 1,4,5-trisphosphate receptor-containing neurons in the brain of the
      weakly electric fish and Western blotting to confirm that a protein similar to
      the inositol 1,4,5-trisphosphate receptor of mammalian brain was recognized in
      the fish brain. In the telencephelon, the dorsal forebrain regions had low
      amounts of inositol 1,4,5-trisphosphate receptor. In the diencephalon, only the
      nucleus tuberis posterior was moderately immunoreactive. In the mesencephalon,
      only the optic tectum contained cells with intense immunoreactivity, similar to
      our findings for the ryanodine receptor (G.K.H. Zupanc, J.A. Airey, L. Maler, J.
      Sutko, and M.H. Ellisman, 1992, J. Comp. Neurol. 325:135-151), which also
      mobilizes intracellular calcium. In the rhombencephalon, a subset of the
      pyramidal cells of the electrosensory lateral line lobe contained inositol 1,4,5
      trisphosphate receptor. These cells have been shown to contain ryanodine receptor
      (Zupanc et al., 1992). However, unlike the ryanodine receptor, the distribution
      of inositol 1,4,5-trisphosphate receptor in these cells is constrained to the
      soma and proximal dendrites. This compartmentalization may indicate the limit of
      the range of second-messenger action. Other regions containing immunoreactive
      cells were the nucleus praeminentialis dorsalis (multipolar and boundary cells),
      nucleus medialis and crista cerebellaris, and the cerebellum, whose Purkinje
      cells were the most intensely labeled. The functional implications of inositol
      1,4,5-trisphosphate receptor localization in the electrosensory lateral line lobe
      are discussed.

PMID- 8550897
TI  - Nitric oxide synthase in tiger salamander retina.
AB  - Previous studies have indicated that nitric oxide, a labile freely diffusible
      biological messenger synthesized by nitric oxide synthase, may modulate light
      transduction and signal transmission in the retina. In the present work, the
      large size of retinal cells in tiger salamander (Ambystoma tigrinum) allowed the
      utilization of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase
      histochemistry and nitric oxide synthase immunocytochemistry to delineate the
      cell-specific intracellular localization of nitric oxide synthase. NADPH
      diaphorase activity was highly concentrated in the outer retina, in rod and cone
      inner segment ellipsoids, and between and adjacent to the photoreceptor cell
      bodies in the outer nuclear layer. Examination of enzymatically isolated retinal
      cells indicated that outer nuclear layer NADPH-diaphorase activity was localized
      to the distal processes of the retinal glial (Muller) cells and to putative
      bipolar cell Landolt clubs. Less intense NADPH-diaphorase activity was seen in
      the photoreceptor inner segment myoid region, in a small number of inner nuclear
      layer cells, in cap-like configurations at the distal poles of cells in the
      ganglion cell layer and surrounding ganglion cell layer somata, and in punctate
      form within both plexiform layers, the pigment epithelium, and the optic nerve.
      Nitric oxide synthase-like immunoreactivity was similarly localized, but was also
      concentrated along a thin sublamina centered within the inner plexiform layer.
      The potential for nitric oxide generation at multiple retinal sites suggests that
      this molecule may play a number of roles in the processing of visual information
      in the retina.

PMID- 8550898
TI  - The rod pathway of the macaque monkey retina: identification of AII-amacrine
      cells with antibodies against calretinin.
AB  - AII-amacrine cells were characterized from Golgi-stained sections and wholemounts
      of the macaque monkey retina. Similar to other mammalian retinae, they are narrow
      field, bistratified amacrine cells with lobular appendages in the outer half of
      the inner plexiform layer (IPL) and a bushy, smoother dendritic tree in the inner
      half. AII cells of the monkey retina were stained immunocytochemically with
      antibodies against the calcium-binding protein calretinin. Their retinal mosaic
      was elaborated, and their density distribution across the retina was measured.
      Convergence within the rod pathway was calculated. Electron microscopy of
      calretinin-immunolabelled sections was used to study the synaptic connections of
      the AII cells. They receive a major input from rod bipolar cells, and their
      output is largely onto cone bipolar cells. Thus, the rod pathway of the primate
      retina follows the general mammalian scheme as it is known from the cat, the
      rabbit, and the rat retina. The spatial sampling properties of macaque AII
      amacrine cells are discussed and related to human scotopic visual acuity.

PMID- 8550899
TI  - Expression of transforming growth factor-alpha-like messenger ribonucleic acid
      transcripts in the bovine mammary gland.
AB  - The objective of this study was to evaluate the expression of mRNA for
      transforming growth factor-alpha in the bovine mammary gland. Total RNA from 23
      cows at various stages of development was isolated from mammary parenchyma and
      subjected to Northern blot analysis using human transforming growth factor-alpha
      32P-labeled deoxycytosine triphosphate cDNA probe. When blots were washed through
      1x sodium chloride and sodium citrate plus 1% SDS at 60 degrees C, a 4.8-kb band
      was observed in all RNA samples. When stringency was increased to .1x, mRNA
      transcripts were observed only for cows at d 233, 240, and 244 of gestation.
      After the high stringency washes, major bands were observed at 7.4 and 3.3 kb and
      minor bands on d 233 at 5.4, 2.3, and 1.6 kb. No additional transcripts were
      detected in RNA from mammary glands of nonpregnant cows during involution,
      lactating cows, or estrogen-treated heifers. These data indicate that transcripts
      similar to transforming growth factor-alpha are present in the bovine mammary
      gland. The expression pattern could represent alternatively spliced transcripts
      that were produced during an important period of mammary development prior to
      parturition.

PMID- 8550900
TI  - Metabolic status and interval to first ovulation in postpartum dairy cows.
AB  - For 21 postpartum dairy cows studied during the period of negative energy
      balance, the rate of muscle protein degradation, gluconeogenic changes,
      circulating large neutral AA, and plasma IGF-I were measured to investigate their
      possible association with the duration of anovulation and LH secretions. Cows
      that ovulated (n = 17) were energetically deficient at first ovulation but were
      approaching a balanced state. The dynamic changes in energy balance, but not the
      mean energy balance or the extent of BW loss, were correlated with days to first
      ovulation. Variations in energy balance were explained largely by variations in
      energy intake. Increased mobilization of body protein was indicated by higher
      concentrations of 3-methylhistidine during the first 3 wk postpartum and was not
      correlated with duration of postpartum anovulation. Plasma aspartate transaminase
      decreased significantly, and the proportion of Tyr to total large neutral AA
      significantly increased in the 12 d prior to first ovulation; both were
      correlated with LH secretion. Plasma IGF-I did not correlate with days to first
      ovulation, but correlated with LH pulse frequency. These findings indicate that
      decreased gluconeogenesis from AA is associated with duration of recovery and
      that Tyr may participate in metabolic signaling to the hypothalamus-hypophyseal
      axis controlling ovarian function in the postpartum dairy cow.

PMID- 8550901
TI  - Extension of corpus luteum lifespan and reduction of uterine secretion of
      prostaglandin F2 alpha of cows in response to recombinant interferon-tau.
AB  - Two experiments tested the effect of recombinant ovine and bovine interferon-tau
      on corpus luteum lifespan, interestrous interval, and oxytocin-induced uterine
      secretion of prostaglandin F2 alpha. Cows received intrauterine injections of 100
      micrograms of recombinant ovine interferon-tau plus 1.4 mg of BSA or of 1.5 mg of
      BSA alone in Experiment 1 and 200 micrograms of recombinant bovine interferon-tau
      plus 1.3 mg of BSA or 1.5 mg of BSA alone in Experiment 2. Twice daily injections
      (0700 and 1900 h) were split evenly between the uterine horns from d 14 to 24 of
      the experimental estrous cycle via an AI pipette in Experiment 1 and via
      intrauterine catheters in Experiment 2. On d 17, cows were injected with 100 IU
      of oxytocin, and plasma was collected for analysis of 13,14-dihydro-15-keto
      prostaglandinF2 alpha. Recombinant ovine interferon-tau extended the lifespan of
      the corpus luteum (27.5 vs. 19.2 d) and interestrous interval (30.5 vs. 20.6 d)
      and abolished the oxytocin-induced increase in 13,14-dihydro-15-keto
      prostaglandinF2 alpha, which peaked at 30 min for the BSA control group (210.8
      pg/ml). Recombinant bovine interferon-tau also extended the lifespan of the
      corpus luteum (29.0 vs. 21.4 d) and interestrous interval (31.5 vs. 22.6 d) and
      abolished the oxytocin-induced increase in 13,14-dihydro-15-keto-prostaglandin F2
      alpha, which peaked at 30 min for the BSA control group (205.6 pg/ml). In
      conclusion, recombinant ovine interferon-tau and recombinant bovine interferon
      tau were effective antiluteolytic agents in cattle.

PMID- 8550902
TI  - Efficacy of a Propionibacterium acnes immunostimulant for treatment of chronic
      Staphylococcus aureus mastitis.
AB  - This study determined the efficacy of treatment of chronic Staphylococcus aureus
      IMI of lactating dairy cows with a biological response modifier consisting of a
      killed preparation of Propionibacterium acnes. Fifty-one lactating dairy cows
      with chronic S. aureus IMI on two commercial dairies were enrolled in a
      controlled, randomized field trial. Twenty-four cows received 1 ml of the
      immunostimulant twice weekly for 4 wk, and the remainder of the cows served as
      untreated controls. Quarter milk samples were collected for SCC from all cows at
      3 and 6 wk after initiation of treatment and for culture at 6 wk after initiation
      of treatment. If samples were negative for S. aureus at 6 wk, cows were sampled
      again for culture 1 wk later for 2 successive d before being considered cured.
      For the cows treated with immunostimulant, 16.7% (36.7% of infected quarters)
      were cured of S. aureus IMI; for the untreated group, 11.1% of cows (32.2% of
      quarters) were cured. The difference was not statistically significant.
      Immunostimulant treatment had no effect on quarter SCC in infected quarters
      overall, but, in those quarters that were cured of S. aureus infection, quarter
      SCC of treated cows tended to be lower than SCC of control cows.

PMID- 8550903
TI  - Differences in bovine lymphocyte antigen associations between immune
      responsiveness and risk of disease following intramammary infection with
      Staphylococcus aureus.
AB  - This study evaluated the relationships between immune response, disease
      resistance, and bovine leukocyte antigens, BoLA, in Holstein cows following
      intramammary challenge with Staphylococcus aureus. This investigation was to
      determine whether immune responsiveness differed between these cows and whether
      differences were related to expression of class I BoLA antigens, which might
      explain the increased resistance or susceptibility to S. aureus mastitis.
      Antibody responses to S. aureus in milk and serum, total IgG1 in milk, and
      blastogenic responses with and without concanavalin A were evaluated. The CA42
      allele, previously associated with increased risk of infection, was relatively
      uninformative for the immune response parameters examined. Other alleles, such as
      W3, were associated with higher milk antibody responses to S. aureus and higher
      milk IgG1 postchallenge. Alleles W7, W4, and W26 were associated with lower milk
      IgG1 and lower antibody titers in serum postchallenge. The association reported
      between allele CA42 and increased risk of S. aureus mastitis did not relate to
      lower antibody or blastogenic responses by these cows; however, indicators of
      innate resistance were not examined. In addition, the different associations
      detected between milk and serum emphasize the importance of considering mucosal
      immunity and unique immunological compartments when searching for relevant
      genetic markers of disease resistance.

PMID- 8550904
TI  - Energy intake and gross efficiency comparisons from calorimetric and field data
      on the same lactating cows.
AB  - Field estimates on gross efficiency were obtained from intake and production data
      on 30 pluriparous Holsteins cows during wk 5, 7, 9, 11, 13, and 15 postpartum.
      Energy intake and efficiency from the energy chamber on the same cows were
      measured during wk 6, 10, and 14 postpartum. Measures of gross efficiency were
      expressed in terms of the utilization of metabolizable energy or net energy for
      lactation and maintenance. Within corresponding postpartum periods, chamber
      measures and field estimates were compared by canonical correlation analysis. All
      estimates from field data of energy and gross efficiencies closely approximated
      measures of the same traits from energy chamber data. Variation among cows in
      traits of energy partition and gross efficiency was similar for field estimates
      and energy chamber measures. Correlations were > .66 between field estimates and
      chamber measures on observations of maintenance energy and milk energy. Field
      estimates and chamber measurements of metabolizable energy and net energy had
      correlations of .76 and .70, respectively.

PMID- 8550905
TI  - Growth and accretion of energy and protein in the gravid uterus during late
      pregnancy in Holstein cows.
AB  - Multiparous Holstein cows (n = 18) were bred artificially to the same bull and
      then slaughtered at times ranging from 190 to 270 d postconception to assess
      accretion of energy, protein, fat, and ash by the conceptus. Wet weights, dry
      weights, and concentrations of energy, CP, crude fat, and ash were obtained for
      the following: fetus, combined amniotic and allantoic fluids, fetal membranes,
      cotyledons, caruncles, and uterine tissues. Rates of accumulation of these
      components in the gravid uterus (sum of all uterine contents) and fetus were
      described by linear or quadratic equations. Estimated rates of accretion of
      energy in the gravid uterus (i.e., conceptus) increased from 567 kcal/d at 190 d
      of gestation to 821 kcal/d at 270 d of gestation; corresponding rates of
      accretion of CP were 62 and 117 g/d. These daily rates represent net energy and
      protein requirements for conceptus growth during late pregnancy in mature
      Holstein cows. Conversion of predicted net energy to metabolizable energy
      requirements for conceptus growth, using the accepted efficiency factor of .14,
      yielded estimates that were consistent with current NRC recommendations.
      Factorial estimation of absorbed protein requirements is hampered by lack of
      precise information on the efficiency with which absorbed AA are deposited in
      conceptus tissues.

PMID- 8550906
TI  - Observations on determination of dysprosium in labeled digesta samples by near
      infrared spectroscopy.
AB  - The objective of this work was to determine whether the Dy content of ruminal
      digesta samples labeled by pulse-dosing intra-ruminally with Dy-labeled forages
      could be determined by near infrared reflectance spectroscopy. Ruminal grab
      samples were obtained from four steers. Equal numbers of alfalfa and orchardgrass
      samples were collected at 17 times (0 to 165 h) after dosing and analyzed (total
      of 272 samples). Dysprosium was determined by direct current plasma emission
      spectrometry. Spectra were obtained by scanning ground samples on a scanning
      monochromator. Calibrations for Dy (0 to 349.5 ppm; mean = 44.5 ppm) were carried
      out using both stepwise and partial least square regressions. Wavelength
      selections using stepwise regression included characteristic Dy wavelengths and
      resulted in R2 and standard error of analysis of approximately .9 and > or = 20
      ppm, respectively. Partial least squares regressions, although more robust, were
      not significantly better. Sample ashing to increase relative Dy concentrations
      did not improve the results. Further investigations indicated that interference
      by Co marker, also present in the samples, was a problem. Although near infrared
      reflectance spectroscopy is capable of determining Dy in labeled forages, further
      work is needed to increase its accuracy.

PMID- 8550907
TI  - Brown midrib sorghum silage for midlactation dairy cows.
AB  - Brown midrib sorghum silage was compared with alfalfa, corn, and normal sorghum
      silages for its effect on performance, ruminal metabolism, and digestive kinetics
      of Holstein dairy cows in midlactation. Twelve cows averaging 90 +/- 5 DIM were
      assigned to one of four diets in replicated 4 x 4 Latin squares with 4-wk
      periods. Additionally, 3 ruminally fistulated cows (95 +/- 20 DIM) were assigned
      to the same diets in a 3 x 4 Youden square for measurement of ruminal
      characteristics. Diets were fed as isonitrogenous TMR that contained 65% silage
      (DM basis). The DMI was greater for the corn and brown midrib sorghum (4% of
      BW/d) than for the alfalfa and normal sorghum diets (3.4% of BW/d). The brown
      midrib sorghum supported FCM production that was similar to that of cows on corn
      and alfalfa diets (25.8 kg/d), but cows fed normal sorghum produced less milk and
      fewer milk components. Source of silage had no effect on eating time, but
      rumination was least for the alfalfa diet. Ruminal pH and ammonia concentrations
      were similar for all diets. Total VFA concentrations were greatest for the corn
      and brown midrib sorghum diets. The brown midrib sorghum had greater in situ
      extent of ruminal NDF digestion than did the normal sorghum, which agreed with in
      vitro data. The brown midrib sorghum used in this experiment supported FCM
      production similar to the corn and alfalfa silages commonly fed to dairy cows in
      midlactation.

PMID- 8550908
TI  - Ruminal fermentation and passage of nutrients to the duodenum of lactating cows
      fed mixtures of corn and barley.
AB  - Five Holstein cows were used in a 5 x 5 Latin square design and fed diets
      containing five different ratios of starch from ground shelled corn and steam
      rolled barley. The DMI decreased and both the proportions of OM and starch
      digested in the rumen increased as barley starch increased in the diet. Corn and
      barley starches fed in a ratio of 75:25 maximized the proportions of ADF and NDF
      digested in the rumen. Replacement of 25% of the corn starch with barley starch
      resulted in the largest increase in the molar percentage of propionate and the
      largest decrease in the molar percentage of acetate in ruminal fluid. Passage of
      NAN to the duodenum was not affected by treatment; however, the percentage of
      nonammonia nonmicrobial N in NAN decreased as barley starch increased. Passage of
      AA to the duodenum was largest when corn and barley starches were fed in ratios
      of 100: 0 and 0:100 because of the influence of DMI and microbial protein
      synthesis. Production of Milk, CP, and SNF was similar when cows were fed diets
      containing corn and barley starches in ratios of 100:0, 75:25, and 50:50 but was
      decreased when the ratios were 25:75 and 0:100. Increased production responses of
      cows when diets contained larger amounts of starch from ground shelled corn were
      probably due to increased DMI.

PMID- 8550909
TI  - Effects of ruminal versus duodenal dosing of fish meal on ruminal fermentation
      and milk composition.
AB  - Three midlactation Holstein cows with ruminal and duodenal cannulas were used in
      a 3 x 3 Latin square design to determine whether ruminal or postruminal
      alterations in metabolism were responsible for the changes in milk composition
      that frequently are associated with dietary fish meal. Cows were offered a diet
      of 60:40 forage to concentrate (aliquots at 6-h intervals) that was supplemented
      with isonitrogenous amounts of soybean meal (1.3 kg of DM/d) dosed into the rumen
      or fish meal (1.0 kg DM/d) dosed either into the rumen or into the duodenum. The
      DMI, ruminal NDF digestion, and flows of total N and microbial N to the duodenum
      decreased for cows receiving fish meal. Dietary N flow increased when fish meal
      was dosed into the rumen. Total concentration of ruminal VFA was greater for cows
      receiving the soybean meal treatment; however, treatment had no effect on the
      ratio of ruminal acetate plus butyrate to propionate. Milk and FCM yields were
      unaffected by treatment, but milk fat content decreased, and milk protein content
      increased when cows were supplemented with fish meal. The difference in mammary
      arteriovenous glucose difference decreased when cows were dosed with fish meal.
      Changes in plasma NEFA and triglycerides were small and inconsistent. Results
      from this experiment suggest that effects of fish meal on milk composition are
      due to postruminal alterations in metabolism.

PMID- 8550910
TI  - Milk fat depression, the glucogenic theory, and trans-C18:1 fatty acids.
AB  - Metabolic and endocrinological characteristics were compared for cows that
      differed in the extent of milk fat depression. Forty-one multiparous Holstein
      cows were fed control (40% concentrate and 60% forage) and high concentrate (80%
      concentrate and 20% forage) diets in a doubale-reversal design. Cows showing one
      or more percentage units of depression in milk fat were arbitrarily classified as
      responders (n = 26); those remaining were classified as nonresponders (n = 15).
      Compared with nonresponders, responders had greater increases in DMI, estimated
      NEL intake and balance, BW, milk yield, protein and lactose yields in milk,
      weight percentage of trans-C18:1 fatty acids in milk, and concentrations of
      triiodothyronine and thyroxine in serum when switched from the control diet to
      the 80% concentrate diet. Lack of an increase in concentrations of glucose and
      insulin in serum of cows with the greatest decline in percentage of milk fat
      casts doubt on the ability of the glucogenic theory to explain milk fat
      depression completely.

PMID- 8550911
TI  - Supplemental niacin and heat-treated whole soybeans for Jersey cows during early
      lactation.
AB  - Fifty-six multiparous Jersey cows were used in a replicated trial to investigate
      the effect of supplemental niacin and heat-treated whole soybeans on milk
      production and composition. Dietary treatments included 0 or 6 g/d of
      supplemental niacin beginning 21 d prior to expected parturition and raw or heat
      treated whole soybeans fed at 10% of the dietary DM beginning immediately after
      parturition. Data were collected for 18 wk following a 2-wk postpartum period
      during which cows were adjusted to experimental diets and allowed to recover from
      parturition. Based on index values for protein dispersibility, heat-treated
      soybeans were marginally heated in yr 1 (12.1) and underheated in yr 2 (17.9).
      Intake of DM from corn silage plus concentrate, alfalfa hay, or soybeans averaged
      15.5, 1.5, and 1.7 kg/d, respectively, and was not different because of niacin
      supplementation or form of soybean. Percentage of milk fat was highest when raw
      soybeans plus niacin were fed and lowest for heat-treated soybeans plus niacin.
      No difference was observed in milk production, milk percentage, or milk protein,
      lactose, and SNF. No advantage was observed from less than optimally heated whole
      soybeans or supplemental niacin in diets for Jersey cows during early lactation.

PMID- 8550912
TI  - The effects of changing ration ingredients on acid-base status, renal function,
      and macromineral metabolism.
AB  - Ten Holstein and 2 Ayrshire cows were used in a switchback design to compare
      diets based on alfalfa haylage and corn silage. Both diets had a similar cation
      anion difference and contained 1% NaHCO3. Dietary treatment did not affect DMI,
      DM digestibility, milk production, or milk composition. Intake, absorption, and
      urinary excretion of N were significantly increased by the ration based on
      haylage, but the overall balance remained unaffected. Cows consuming haylage
      absorbed and excreted significantly more water than did cows consuming corn
      silage and consequently had significantly larger urine volumes. Blood volume was
      increased by the ration based on haylage. Intakes of Mg, K, Cl, and S differed
      between diets, but only K balance was increased by the diet based on haylage. The
      fractional excretion of K, Cl, and S in urine was increased by the diet based on
      haylage, demonstrating that the kidneys responded to the increased intakes by
      diminishing the reabsorption or by increasing the secretion of these minerals.
      Acid-base parameters for blood, urine, and milk were unaffected by dietary
      treatment. A diet based on alfalfa haylage, compared with a diet based on corn
      silage with similar cation-anion difference, resulted in different water and
      mineral metabolism but did not affect the acid-base status of cows in early
      lactation.

PMID- 8550913
TI  - Effect of processing sorghum grain on dairy calf performance.
AB  - Two trials evaluated the effect of sorghum grain processing on dairy calf
      performance. In trial 1, Holstein calves (n = 76; .5 to 8 wk of age) were fed one
      of three calf starters that contained either raw, roasted (exit temperature of
      135 degrees C), or conglomerated sorghum grain. The conglomeration process
      consisted of grinding the grain, adding water, pelleting the mixture, and then
      roasting it. Raw and roasted sorghum grains were ground through a 3.2-mm screen
      and then included in complete pelleted starters; conglomerated sorghum grain
      pellets were mixed with the other pelleted ingredients of the starter. Processing
      did not enhance calf performance or affect selected ruminal and blood
      metabolites. In trial 2, roasted and conglomerated sorghum grains were ground
      through a 3.2-mm screen, and each was included in a pelleted starter fed for ad
      libitum intake to Holstein calves (n = 48) from .5 to 8 wk of age. Calf
      performance was not affected by method of grain processing, and ruminal and blood
      metabolites were similar; however, 22% of calves on the conglomerated sorghum
      grain starter bloated during the postweaning period, which probably resulted in
      reduced feed intake from wk 6 to 8. Measures to prevent bloat may be necessary to
      realize a potential benefit of conglomerating sorghum grain for calves.

PMID- 8550914
TI  - Associations between casein haplotypes and milk yield traits.
AB  - The genotyping of 13 sires and 250 of their sons for casein polymorphisms
      revealed 10 different haplotypes for Norwegian Cattle. Associations between
      haplotypes and yields of protein, milk, and fat were studied using a
      granddaughter design. Three subsets of data containing families with haplotypes
      1, 5, and 10 were analyzed independently and denoted by analyses 1, 5, and 10,
      respectively. In addition, all sire families of all haplotypes were pooled and
      analyzed in analysis T. No associations were found between haplotypes and traits
      for milk yield in analyses 1, 10, and T. However, the null hypothesis of an equal
      effect within sire of bulls was rejected in analysis 5 for yields of protein and
      milk. The increase in protein yield associated with haplotype 5 ranged from 2.52
      to 14.58 kg (from .09 to .51 phenotypic standard deviations). These results may
      indicate the presence of at least one quantitative trait locus in the region of
      the casein genes that affects protein yield of Norwegian Cattle. The findings
      were confirmed with a new analysis of two large sire families segregating
      haplotype 5 (analysis 5N).

PMID- 8550915
TI  - Accuracy of predicting genetic merit from pedigree information for bulls entering
      stud sampling programs.
AB  - Four sources of pedigree information were used to determine the most accurate
      prediction of daughter yield deviation and PTA milk, fat, and protein for AI
      sampled bulls (birth years from 1984 to 1986). Pedigree sources compared were
      parent average, pedigree index, PTA of sire, and PTA of sire and dam. Bulls were
      included only if they did not have a USDA evaluation in July 1989, so that a
      parent average was nearly uninfluenced by daughters of the bull. When pedigree
      estimates from immediately prior to first evaluation were used, parent average
      was a better predictor than pedigree index. Inclusion of PTA of dam with PTA of
      sire was more accurate than PTA of sire alone for predicting each trait and
      resulted in R2 comparable with parent average. Predictability of daughter yield
      deviation from parent average for each trait improved over time as the amount of
      daughter information increased. Regression coefficients and R2 increased
      considerably for parent average and PTA of dam but not for pedigree index or PTA
      of sire when evaluations of young bulls began influencing estimates for their
      ancestors. Parent average was always a better predictor than pedigree index.
      Although animal model evaluations of cows have improved predictive value,
      regression coefficients for all pedigree sources were less than theoretically
      expected.

PMID- 8550916
TI  - Survey of dairy managers in the Pacific Northwest identifying factors associated
      with teat chapping.
AB  - Telephone interviews were conducted to evaluate the association of teat chapping
      with combinations of premilking and postmilking teat disinfectants (predip and
      postdip), other management practices, and climatic conditions. Holstein dairies
      (n = 100) in the DHIA SCC program were randomly selected from three northwest
      regions. During nonwinter seasons, herd managers using an iodophor dip without
      skin conditioner both premilking and postmilking were 9.7 times more likely to
      report chapping than were those using iodophor with conditioner. The herd
      managers least likely to report chapping problems were those using conditioner in
      both the predip and postdip. Use of conditioner in postdip only was associated
      with intermediate frequency of reported chapping. No conditioner in either predip
      or postdip was associated with the greatest frequency of reported chapping. Herd
      managers using a different germicide in the predip and postdip reported more
      chapping than herd managers using the same germicide. The frequency of chapping
      was highest during winter in all regions, and the percentage of herd managers
      reporting chapping within a region was associated with the temperature extremes
      of the region. For seasons other than winter, characteristics of predip and
      postdip combinations and parlor exit or barn design were the management factors
      that best described an association with reported chapping.

PMID- 8550917
TI  - Segregation or use of separate milking units for cows infected with
      Staphylococcus aureus: effects on prevalence of infection and bulk tank somatic
      cell count.
AB  - Dairy herds (n = 76) with an initial prevalence of Staphylococcus aureus IMI > or
      = 10% were included in this study. Criteria were that herds did not change teat
      dipping or dry cow treatment practices, did not segregate cows that were positive
      for S. aureus at the initial visit, and did not cull > 50% of cows found to be
      positive on the initial visit. During a follow-up period (6 to 24 mo),
      segregation or separate milking of cows that were positive for S. aureus reduced
      prevalence from 29.5 to 16.3% and bulk tank SCC from 600,000 to 345,000/ml.
      Prevalence of S. aureus mastitis was unchanged for herds that did not segregate
      cows with S. aureus, 22.5 to 20.2%, and the reduction in SCC from 698,000 to
      484,000 for nonsegregated herds was also smaller. Segregation of cows that were
      known to be positive for S. aureus is an effective mastitis control practice.

PMID- 8550918
TI  - Financial analysis of alternative treatments for clinical mastitis associated
      with environmental pathogens.
AB  - For two large California dairy herds with twice daily milking, 171 infected
      quarters of lactating cows with mild clinical mastitis were randomly assigned to
      one of three treatment groups. Group A (50 cows) was treated with 62.5 mg of
      intramammary amoxicillin every 12 h for three milkings. Group C (50 cows) was
      treated with 200 mg of intramammary cephapirin every 12 h for two milkings. Group
      O (71 cows) was treated with 100 U of intramuscular oxytocin every 12 h for three
      milkings. Clinical cure rates did not differ among treatment groups. The cost per
      episode of clinical mastitis was higher ($54.47) for group C than for groups A
      ($38.53) or O ($34.88). Group O had a higher incidence of relapse (41%), and a
      greater percentage of group O cows (65%) experienced an additional mastitic event
      in the enrolled lactation than did cows in groups A and C. Treatment had no
      effect on the mean number of nonsalable milkings (24.7) associated with mastitis
      in the lactation interval subsequent to enrollment on the trial. Twenty-two
      percent of the cows accrued more than 30 nonsalable milkings and produced 55% of
      the total nonsalable milkings associated with mastitis. There was no treatment
      effect on total milk production, fat production, or time to removal of the
      enrolled cows from the herd.

PMID- 8550919
TI  - A rhetoric of concern.

PMID- 8550920
TI  - The impacted maxillary canine: I. Review of concepts.
AB  - This first of the two papers dealing with impaction of the maxillary canines
      explores the etiology of the most frequently encountered and treated dental
      impactions. Developmental events believed to play a significant role in the
      etiology of impactions, together with diagnostic methods of localization, as well
      as the available preventive measures are reviewed. Our second paper deals with
      the clinical management of the maxillary impacted canines.

PMID- 8550921
TI  - The impacted maxillary canine: II. Clinical approaches and solutions.

PMID- 8550922
TI  - Sealant status and factors associated with sealant presence among children in
      Milwaukee, WI.
AB  - To determine the percent of school-children aged 6-14 years with sealants placed
      in their permanent molars in the City of Milwaukee. 2) To describe factors
      associated with sealant presence among these children. 3) To describe
      differences, if any, among ethnic majority and minority groups. Twelve public
      schools agreed to participate in this project. After consent forms were obtained,
      1,234 dental exams were performed. A 15-item pretested questionnaire was given to
      each child to take home for the parent(s) to complete. Response rate was 60
      percent (N = 742). Data were analyzed using frequencies and Chi-Square tests (P
      value < 0.05). Only 9.6 percent of the sample had sealants on their permanent
      molars. Variables that were found associated with children more likely to have
      sealants included: gender (female children more likely than males); children with
      a recent dental exam; children having a regular dentist; parents having heard
      about sealants before this study; parents' correct knowledge regarding the
      purpose of sealants; higher level of parents' education; higher parents' total
      annual income; ethnicity (Caucasian children more likely than Hispanic, African
      American, American Indian, or Asian children); and age (children in the older
      group, 10-14 years, more likely than children in the younger group, 6-9 years).
      Percent of school-children with sealants on their permanent molars in the city of
      Milwaukee is low. Efforts are needed to increase the knowledge of sealants by the
      general public as well as to promote sealant use by dentists in both private
      practice and public health programs, especially for minority children.

PMID- 8550923
TI  - Partial pulpotomy: another treatment option for cariously exposed permanent
      molars.

PMID- 8550924
TI  - Toothbrushing ability is related to age in children.
AB  - Methods to assess toothbrushing ability vary. The purpose of this study was to
      determine whether age could be a predictor for toothbrushing ability in children.
      This study evaluated the brushing patterns of 122 children utilizing the
      horizontal scrub technique. The results obtained suggest that a child's age is a
      reasonable predictor for toothbrushing ability.

PMID- 8550925
TI  - Incidence of dental caries in children with acute lymphoblastic leukemia is
      related to the therapy used.
AB  - Dental caries is an infectious disease and it may be harmful for children
      suffering from leukemia. DMFS, DMFT scores of forty-five children with acute
      lymphoblastic leukemia (ALL) were significantly higher than in healthy age-and
      sex-matched controls after cessation of therapy. The children with CNS
      irradiation had higher DMFT (7.13 than children with only chemotherapy (3.4) and
      the controls (1.8). Lifelong caries incidence showed that children with ALL had
      2.7 new caries lesions per year during the therapy compared to the 1.1 (p < 0.05)
      new lesions in controls. More detailed analysis of permanent anterior teeth at
      the age of twelve years showed that all patient groups had more filled anterior
      teeth than controls (p < 0.001); and children with bone marrow transplantation
      had significantly more fillings than the other two groups.

PMID- 8550926
TI  - Anterior tooth trauma in eleven-year-old South African children.
AB  - Little new evidence on the prevalence of injury to the anterior teeth of children
      has been reported in the past five years and, in South Africa, trauma to the
      teeth of children in different ethnic groups has not been compared respectively.
      The purpose of this investigation was to determine the prevalence of dental
      trauma using well-defined criteria and to sample a specific age-group. Five
      regions were chosen and 1035 children in the eleven-year age-group were examined.
      No statistical significance was found between the ethnic groups related to the
      amount of injury sustained. For all groups, boys received more injuries than
      girls. The most common injury was fracture of the enamel of the maxillary central
      incisor. With 15 percent of the children receiving some level of trauma by age
      eleven years, this is one of the main dental treatment needs for South African
      children.

PMID- 8550927
TI  - Pediatric dental practice: the number of your employees is increasing.
AB  - Dental practice arrangements are changing. There are proportionately fewer solo
      practices and increasing numbers of practices with many more employees. A review
      is provided of this evolving world of dentistry-including pediatric dental
      practice.

PMID- 8550928
TI  - Accessory jaw and mouth: report of case.
AB  - A rare case of teratoma, presented with a double mandible and double mouth,
      mucous secretions and two teeth erupting in the accessory mouth. There are
      numerous supernumerary teeth in the main body of the mandible, and geminated
      primary teeth in the mandibular arch. There was a history of cleft palate.

PMID- 8550929
TI  - Mercury hypersensitivity from amalgam: report of case.
AB  - Mercury hypersensitivity is an allergic response mediated by the immune system.
      allergic reactions to mercury and other constituents of amalgam have been
      documented, but are very rare. The common symptoms are dermatitis, eczema,
      urticaria, erythema, edema and itching, occurring primarily on the face, neck,
      limbs and upper torso. In this paper an interesting case of mercury
      hypersensitivity is investigated and discussed.

PMID- 8550930
TI  - Acoustic properties of selected bovine tissues in the frequency range 20-200 MHz.
AB  - The acoustic properties of freshly excised bovine liver, heart muscle, and fat
      are characterized in the frequency range 20-200 MHz by the bioultrasonic
      spectroscopy system using an ultrasonic transmission comparison method.
      Significant differences are obtained in the attenuation coefficient, velocity,
      impedance, and density among these tissues. Measurements of aqueous solutions of
      bovine hemoglobin are also reported in order to compare the contribution of the
      protein content to the acoustic properties. The differences among the acoustic
      properties of liver and heart muscle can be described in terms of their protein
      contents and other molecular constituents.

PMID- 8550931
TI  - On a fractal packing approach for understanding ultrasonic backscattering from
      blood.
AB  - A new theoretical model is proposed to explain the change in the backscattered
      Doppler power with flow conditions. It defines a fractional packing dimension to
      represent the manner in which red blood cells are packed and this in turn is
      related to the variance of the scatterer number density. An explicit expression
      for the packing factor in terms of the integral of the pair correlation function
      is presented. Comparison of published experimental results for the backscattered
      power versus hematocrit with the theoretical model suggests that turbulence
      reduces the packing dimension. This reduction reflects a modification of the pair
      correlation function caused by changes in the flow field.

PMID- 8550932
TI  - Wave space resolution in ultrasonic scattering measurements.
AB  - The spatial-frequency spectra of the spatial properties of a scattering medium
      can be determined from measurements of scattering over a number of angles or
      frequencies. In such measurements, the spatial localization associated with
      transducer beam patterns and time gates causes an uncertainty in the measured
      spatial-frequency domain properties of the scatterer. This uncertainty is
      analyzed using an analytic and computational model in which system effects are
      represented by a spatial-frequency domain function. Wave space resolution in a
      particular direction is shown to be inversely proportional to the spatial
      frequency spread of the system function in that direction. In the backscatter
      case, wave space resolution is limited in the direction of the scattering vector
      by a convolution of the emitted pulse and the detector time gate, and resolution
      in the lateral direction depends mainly on the transducer aperture, increasing
      approximately in proportion to the aperture diameter. In the case of backscatter
      measurements, smooth aperture apodization improves lateral resolution somewhat
      but has little effect on resolution in the direction of the scattering vector.
      For angular scattering measurements, resolution in all directions depends on both
      the aperture size and (for sufficiently short time gates) on the time gates
      employed. Illustration of the practical importance of wave space resolution is
      provided using analysis of two previously published tissue characterization
      experiments.

PMID- 8550933
TI  - Mechanically coupled ears for directional hearing in the parasitoid fly Ormia
      ochracea.
AB  - An analysis is presented of the mechanical response to a sound field of the ears
      of the parasitoid fly Ormia ochracea. This animal shows a remarkable ability to
      detect the direction of an incident sound stimulus even though its acoustic
      sensory organs are in very close proximity to each other. This close proximity
      causes the arrival times of the sound pressures at the two ears to be less than 1
      to 2 microseconds depending on the direction of propagation of the sound wave.
      The small differences in these two pressures must be processed by the animal in
      order to determine the incident direction of the sound. In this fly, the ears are
      so close together that they are actually joined by a cuticular structure which
      couples their motion mechanically and subsequently magnifies interaural
      differences. The use of a cuticular structure as a means to couple the ears to
      achieve directional sensitivity is novel and has not been reported in previous
      studies of directional hearing. An analytical model of the mechanical response of
      the ear to a sound stimulus is proposed which supports the claim that mechanical
      interaural coupling is the key to this animal's ability to localize sound
      sources. Predicted results for sound fields having a range of incident directions
      are presented and are found to agree very well with measurements.

PMID- 8550934
TI  - The perceptual representation of voice gender.
AB  - The perceptual representation of voice gender was examined with two experimental
      paradigms: identification/discrimination and selective adaptation. The results
      from the identification and discrimination of a synthetic male-female voice
      continuum indicated that voice gender perception was not categorical. In
      addition, results from selective adaptation experiments with natural and
      synthetic voice stimuli indicated that the perceptual representation of voice
      adapted is an auditory-based representation. Overall, these findings suggest that
      the perceptual representation of voice gender is auditory based and is
      qualitatively different from the representation of phonetic information.

PMID- 8550935
TI  - Phonemic resetting versus postural adjustments in the speech of cochlear implant
      users: an exploration of voice-onset time.
AB  - Voice-onset time (VOT) was measured in plosive-initial syllables uttered by five
      cochlear implant users prior to and repeatedly at intervals after activation of
      their speech processors. In "short-term" experiments, the elicitation set was
      read after the subject's processor has been off for 24 h, then turned on them off
      again. Four out of five implant users increased voiceless and/or voiced VOTc (VOT
      corrected for changes in syllable duration) from preimplant baselines to final
      recordings made 1-3 years later. Measured acoustic correlates of speech "posture"
      (average SPL, F0, and low-frequency spectral slope) changed concurrently. Results
      in the short-term study were largely consistent with the long term. Significant
      multiple regressions relating changes in VOTc to accompanying changes in postural
      correlates were found in both studies. This outcome is consistent with hypotheses
      that predict changes in both VOTc and in postural correlates with the restoration
      of some hearing and that allow for linkages between the two. Some of the reliable
      VOTc increases obtained over the long term that were not correlated with postural
      changes may have been caused directly by auditory validation of
      articulatory/acoustic relations that underlie synergisms for phoneme production.

PMID- 8550936
TI  - A head and transducer support system for making ultrasound images of tongue/jaw
      movement.
AB  - A head and transducer support system (HATS) was developed for use in ultrasound
      imaging of tongue movement. Ultrasound is an imaging technique that captures
      tongue motion during speech and thus has great appeal as a tool for speech
      research. However, because ultrasound systems are designed for clinical use, the
      transducer is hand-held and it is almost impossible to hold it completely steady
      under the chin when collecting tongue data. A system was needed to fix the head
      and support the transducer under the chin in a known position without disturbing
      speech. The HATS system was designed, constructed, and modified to provide valid,
      reliable tongue movement data by (1) immobilizing the head and (2) positioning
      the ultrasound transducer in a known relationship to the head.

PMID- 8550937
TI  - Growth of low-pass masking of pure tones and speech for hearing-impaired and
      normal-hearing listeners.
AB  - Tonal thresholds and consonant recognition were measured in low-pass maskers as a
      function of masker bandwidth and spectrum level. Thresholds and consonant
      recognition scores were obtained for normal-hearing subjects, and for pairs of
      normal-hearing subjects (who listened in threshold-equating background noise) and
      hearing-impaired subjects. Consonant-recognition scores were compared to scores
      predicted by a modified articulation index. Mean thresholds measured in low-pass
      maskers were higher for hearing-impaired than for normal-hearing subjects for
      signal frequencies above the masker. Slopes of functions relating thresholds for
      signals above the masker to masker spectrum level were not significantly
      different between hearing-impaired and normal-hearing subjects listening in
      spectrally shaped broadband noise (SSBB), but were shallower than slopes of
      masking functions for normal-hearing subjects listening without SSBB. Slopes of
      masking functions for signals within the masker were equivalent for all subjects.
      Slopes of functions relating consonant recognition to masker spectrum level were
      similar within subject pairs, whereas, in some cases, slopes of functions
      relating consonant recognition to speech level were shallower for hearing
      impaired subjects than for their normal-hearing counterparts. Although greater
      improvement in consonant recognition with speech level was predicted for hearing
      impaired than for normal-hearing subjects, on average, less improvement with
      speech level was observed. Shallower slopes of functions relating score to speech
      level observed for some hearing-impaired listeners may result from more shallow
      growth of speech sensation levels in spectral regions above the low-pass masker.

PMID- 8550938
TI  - On measuring psychometric functions: a comparison of the constant-stimulus and
      adaptive up-down methods.
AB  - Psychometric functions were obtained using the conventional constant-stimulus
      method and an adaptive up-down method, for both computer-simulated and human
      observers. Except when the stimuli are closely placed, psychometric functions
      obtained with the adaptive method are as accurate as those obtained with the
      constant-stimulus method. Empirically, the adaptive method has some potential
      advantages owing to its ability to automatically concentrate the trials within
      the dynamic range of the psychometric function. It needs no pilot measurements
      for setting the signals as required by the constant-stimulus method. Furthermore,
      following a marked change in the underlying psychometric function, the
      distribution of the trials is automatically readjusted. Thus, on the basis of
      empirical considerations, the adaptive method is a better choice than the
      constant-stimulus method for measuring psychometric functions.

PMID- 8550939
TI  - Age effects on duration discrimination with simple and complex stimuli.
AB  - This study examined age-related changes in temporal processing by measuring DLs
      for signal duration using simple and complex stimuli. Previous research has shown
      that elderly listeners exhibit difficulty discriminating duration changes in
      simple sounds, suggesting the possibility of age-related changes in central
      timing mechanisms. The present experiments examined the interactive effects of
      aging, hearing loss, and stimulus complexity on duration discrimination. Four
      groups participated: young and elderly listeners with normal hearing, and young
      and elderly listeners with hearing loss. Duration DLs were measured for 250-ms
      tone bursts and for silent gaps between tone bursts that were presented either in
      isolation or embedded as target stimuli within tonal sequences. The tone
      sequences were composed of five sequential 250-ms components. Stimulus complexity
      was varied by changing the sequential order of tone frequencies and the location
      of an embedded target component across listening conditions. Analyses of results
      revealed the following: Elderly listeners performed more poorly than younger
      listeners in nearly all stimulus conditions, the effects of stimulus complexity
      on discrimination were greatest among elderly listeners, and hearing loss had no
      systematic effect on discrimination performance.

PMID- 8550940
TI  - Lateralization of comodulated complex waveforms.
AB  - This study examines the ability to lateralize a complex signal characterized by
      correlated temporal activity across widely separated frequency regions. The high
      frequency complex consisted of two narrow-band stimuli. The two stimuli had
      common interaural delays but different carriers centered on nonoverlapping
      critical bands. Two basic conditions were examined: The narrow-band stimuli had
      temporal envelopes which were (1) identical or (2) different. In the first
      experiment, narrow bands of noise were used which either had identical temporal
      envelopes (comodulated) or statistically independent envelopes (CFs = 2550 and
      3350 Hz). In the second experiment, two sinusoidally amplitude-modulated (SAM)
      tones were used whose modulators either had the same starting phase or a
      different starting phase (CFs = 2550 and 4000 Hz). Results of the first
      experiment showed that for bandwidths narrower than 300 Hz, comodulated bands
      produced significantly lower interaural-delay thresholds compared to independent
      bands. Results of the second experiment showed that when the two SAM tones (100
      Hz modulation rate) had the same modulator starting phase, interaural-delay
      thresholds were lowest.

PMID- 8550941
TI  - Villchur revisited: another look at automatic gain control simulation of
      recruiting hearing loss.
AB  - An algorithm to simulate the effects of sensorineural hearing impairment on
      speech reception was investigated. Like that described by Villchur [J. Acoust.
      Soc. Am. 62, 665-674 (1977)], this simulation employs automatic gain control in
      independent frequency bands to reproduce the elevated audibility thresholds and
      loudness recruitment that are characteristic of this type of loss. In the present
      implementation, band gains are controlled in an effort to simulate loudness
      recruitment directly, using recruitment functions that depend only on the
      magnitude of hearing loss in the band. In a preliminary evaluation, two normal
      hearing subjects listened to the simulation matched to hearing losses studied
      previously [Zurek and Delhorne, J. Acoust. Soc. Am. 82, 1548-1559 (1987)] with
      noise-masking simulations. This evaluation indicated that the present automatic
      gain control simulation yielded scores roughly similar to those of both the
      hearing-impaired listeners and the masked-normal listeners. In the more-detailed
      evaluation, the performance of three listeners with severe sensorineural hearing
      loss on several speech intelligibility tests was compared to that of normal
      hearing subjects listening to the output of the simulation. These tests included
      consonant-vowel syllable identification and sentence keyword identification for
      several combinations of speech-to-noise ratio, frequency-gain characteristic, and
      overall level. Generally, the simulation algorithm reproduced speech
      intelligibility well, though there was a clear trend for the simulation to result
      in better intelligibility than observed for impaired listeners when high
      frequency emphasis placed more of the speech spectrum above threshold at higher
      frequencies. Also, the hearing-impaired listener with the greatest loss showed
      the largest discrepancies with the simulation. Overall, however, the simulation
      provides a very good approximation to speech reception by hearing-impaired
      listeners. The results of this study, together with previous studies of noise
      making simulation, suggest that threshold elevation and recruitment, which are
      necessary features of a simulation of cochlear hearing loss, can also be largely
      sufficient for simulating the speech-reception performance of listeners with
      moderate to severe hearing impairments.

PMID- 8550942
TI  - Effect of release time in compression hearing aids: paired-comparison judgments
      of quality.
AB  - Paired-comparison judgments of quality were obtained from 20 hearing-impaired
      listeners for speech processed through simulated compression hearing aids varying
      in release time (60, 200, 1000 ms) at three different compression ratios (1.5, 2,
      3:1) and for three different background noises (ventilation, apartment,
      cafeteria). Analysis revealed that the main effect of release time did not have a
      significant effect on perceived quality. The interaction between release time and
      noise type was found to be significant. While no significant difference in
      preference for release times was evident for the ventilation noise, the longer
      release times (200 and 1000 ms) were preferred for the higher level noises
      (apartment noise, cafeteria noise). Post hoc testing revealed that the mean
      preference scores for the 200- and 1000-ms release time were significantly
      greater than that of the 60-ms release time with the competing cafeteria noise (p
      < 0.05). Analysis of individual subject data revealed statistically significant
      preferences that differed from the group mean, suggesting that individualized
      fitting of this parameter of a compression hearing aid might be warranted.

PMID- 8550943
TI  - Vibrotactile forward masking: effects of the amplitude and duration of the
      masking stimulus.
AB  - Tactile thresholds for detecting a 50-ms signal presented 25 ms after the
      termination of a masking stimulus increased as a function of the amplitude level
      and duration of the masking stimulus. The effects were similar in both the P and
      NP I channels measured at 250 and 20 Hz, respectively. It was concluded that the
      increased masking caused by increasing the duration of the masking stimulus
      resulted from processes other than or in addition to temporal integration--the
      latter being a characteristic of the P, but not the NP I, channel. The slopes of
      the masking functions, in which threshold shifts were plotted as a function of
      masking-stimulus sensation level, were consistently greater for 20-Hz than for
      the 250-Hz stimuli, suggesting that masking efficiency is greater in the NP I
      than in the P channel.

PMID- 8550944
TI  - Some temporal parameters in vibrotactile forward masking.
AB  - Tactile thresholds for detecting a 250-Hz signal of variable duration presented
      at variable times after the termination of a 250-Hz 700-ms masking stimulus were
      measured. It was found that the threshold shift resulting from the presentation
      of the masking stimulus declined as functions of the duration of the signal and
      the duration of the time interval between the masking stimulus and signal. Both
      of these effects were found to be attributable to an increase in the time
      interval between the offset of the masking stimulus and the offset of the signal.

PMID- 8550945
TI  - Effects of ear-canal standing waves on measurements of distortion-product
      otoacoustic emissions.
AB  - At frequencies above 3 kHz, standing waves in the ear canal complicate
      calibration of stimulus sound-pressure levels (SPLs) for measurements of
      distortion-product otoacoustic emissions (DPOAEs). In the literature, two
      stimulus-presentation strategies have been used for DPOAE measurements. In the
      "in-the-ear adjustment" strategy, the voltage command to the speakers is adjusted
      to maintain a constant stimulus SPL across frequency at the DPOAE-measurement
      microphone. In the "iso-voltage" strategy, the voltage presented to the speakers
      is held constant across frequency, on the basis of the assumption that the
      frequency response of the speakers is approximately flat at the eardrum in the
      average human ear canal. Because of standing-wave effects, there are large,
      systematic but idiosyncratic differences of stimulus SPL between the two
      strategies. DPOAE-versus-frequency functions ("DPOAE audiograms") obtained using
      both stimulus-presentation strategies in the same ears are presented. The
      differences of stimulus SPL between the two strategies, and the associated
      differences of DPOAE amplitude, are described and quantified. Around frequencies
      of standing-wave minima at the DPOAE probe, the in-the-ear adjustment strategy
      resulted in smaller DPOAEs at high L1 = L2, but much larger DPOAEs at low L1 =
      L2, than did the iso-voltage strategy. For any L1, the DPOAE-amplitude
      differences between the two strategies varied systematically with L1-L2. At the
      stimulus levels used to construct previously published population norms for
      clinical applications (i.e., L1 > or = 65 dB SPL), there are only small
      differences of mean DPOAE amplitudes, and of the standard deviations of these
      means, between the two strategies.

PMID- 8550946
TI  - Distortion-product otoacoustic emissions in Mongolian gerbils with resistance to
      noise-induced hearing loss.
AB  - Distortion-product otoacoustic emissions (DPOAEs) and the endocochlear potential
      (EP) were recorded in adult Mongolian gerbils exposed to noise for either 1 or 12
      days. The exposure was an octave band of noise centered at 4 kHz at 80 dB SPL
      with a duty cycle of 6 h on, 18 h off. A previous study showed that a single such
      exposure causes 20-50 dB of temporary threshold shift (TTS) in the neural
      response at 4-8 kHz, but that the TTS is reduced to less than 10 dB following 12
      daily exposures [Boettcher, J. Acoust. Soc. Am. 94, 3207-3214 (1993)]. This
      reduction in TTS is commonly referred to as resistance to noise-induced hearing
      loss (NIHL). To further analyze whether resistance to NIHL is caused by changes
      in the outer hair cell (OHC) system or the lateral wall system (or both), DPOAEs
      and EPs were measured in the exposed ears. The amplitudes of DPOAEs were
      significantly reduced in the frequency region from 4 to 10 kHz in subjects
      exposed to noise for 1 day, but were relatively normal in subjects exposed for 12
      days. DPOAE amplitudes from frequency regions below the spectrum of the exposure
      were similar across the exposure and control groups except at the low-frequency
      edge of the noise where DPOAE amplitudes were consistently higher than normal in
      the exposed animals. The EP values in both exposure groups were not reduced from
      normal, unexposed levels. Thus there was no causal relationship between changes
      in the EP and the reduction of the DPOAE amplitudes. These data suggest that the
      development of resistance to noise is related to an initial depression of OHC
      activity followed by a recovery of activity to a stable level, despite an ongoing
      exposure.

PMID- 8550947
TI  - Rate representation and discriminability of second formant frequencies for
      /epsilon/-like steady-state vowels in cat auditory nerve.
AB  - Alternate forms of the steady-state vowel /epsilon/ with second formant peaks
      located at 1400, 1500, 1700, and 2000 Hz were used to study the representation
      and discrimination of second formant frequencies at the level of the auditory
      nerve. Recordings from large populations of auditory nerve fibers in response to
      these stimuli were used to create rate-place plots, which show second formant
      peaks that resembled the stimulus spectra. Measures of the peak amplitude
      decreased as sound level was increased and as second formant frequency was
      lowered. Representation of the spectra was degraded at the higher sound level
      because of saturation and two-tone suppressive effects. However, formant peaks
      were clearly represented in plots of rate differences between two vowels. Such
      plots resemble the ratio of the magnitudes of the two vowel spectra. The results
      suggest that information concerning the position of formant peaks is present in
      the average discharge rate of the auditory nerve. A measure of discriminability,
      d', between vowel pairs was also calculated. Second formants differing by 125-240
      hz can be discriminated using the rate responses of individual fibers that are
      optimally placed on the basilar membrane; the estimated second formant jnd for
      the whole auditory nerve is approximately 1 Hz.

PMID- 8550948
TI  - Analog neural network-based helicopter gearbox health monitoring system.
AB  - The development of a reliable helicopter gearbox health monitoring system (HMS)
      has been the subject of considerable research over the past 15 years. The
      deployment of such a system could lead to a significant saving in lives and
      vehicles as well as dramatically reduce the cost of helicopter maintenance.
      Recent research results indicate that a neural network-based system could provide
      a viable solution to the problem. This paper presents two neural network-based
      realizations of an HMS system. A hybrid (digital/analog) neural system is
      proposed as an extremely accurate off-line monitoring tool used to reduce
      helicopter gearbox maintenance costs. In addition, an all analog neural network
      is proposed as a real-time helicopter gearbox fault monitor that can exploit the
      ability of an analog neural network to directly compute the discrete Fourier
      transform (DFT) as a sum of weighted samples. Hardware performance results are
      obtained using the Integrated Neural Computing Architecture (INCA/1) analog
      neural network platform that was designed and developed at The Charles Stark
      Draper Laboratory. The results indicate that it is possible to achieve a 100%
      fault detection rate with 0% false alarm rate by performing a DFT directly on the
      first layer of INCA/1 followed by a small-size two-layer feed-forward neural
      network and a simple post-processing majority voting stage.

PMID- 8550949
TI  - An interferometric technique for B/A measurement.
AB  - An isentropic phase method is described for measuring in vitro the acoustic
      nonlinearity parameter B/A of several aqueous buffers, protein solutions, lipid
      oils, and emulsions. The technique relies upon the use of an acoustic
      interferometer to measure the small changes in sound speed that accompany a rapid
      hydrostatic pressure change of between one and two atmospheres. Average
      accuracies of 0.85% are attainable with this method.

PMID- 8550950
TI  - Measurements of harmonic generation in a focused finite-amplitude sound beam.
AB  - Measurements of harmonic generation in the sound field radiated by a focused
      circular piston source are compared with numerical calculations based on the
      nonlinear parabolic wave equation. The large dynamic range and high spatial
      resolution of the measurements enable precise comparisons to be made with the
      theoretical predictions.

PMID- 8550951
TI  - Complex and rapid-cycling in bipolar children and adolescents: a preliminary
      study.
AB  - 26 subjects aged 7-18 years were studied. Diagnoses of bipolar disorders were
      established using the Kiddie-Schedule for Affective Disorders and Schizophrenia
      Present Episode Version-1986 modified for DSM-III-R criteria and for rating the
      number and duration of manic and hypomanic episodes. Complex cycling patterns
      were observed. These included numerous brief episodes suggesting continuous rapid
      cycling in 80.8% of cases. Mean age of onset was early (8.5 +/- 4.4 years).
      Psychotic phenomena, suicidality, hyperactivity and 'mixed mania' were highly
      prevalent. Data in this report provide support for complex and rapid-cycling
      patterns in childhood onset bipolar disorder.

PMID- 8550952
TI  - Personality pathology among married adults with bipolar disorder.
AB  - The comorbidity of DSM-III-R axis II personality disorders in patients with
      bipolar disorder has received less attention than for unipolar depression perhaps
      because of the potential confounding of state vs. trait qualities. The current
      study took steps to separate pathological traits of personality from behaviors
      evidenced during discrete affective episodes in a sample of married, outpatient
      bipolar patients. Data indicated that 22% of our patients met criteria for a
      categorical diagnosis of personality disorder. Axis II pathology as represented
      by both categorical and dimensional scores was associated with increased
      psychiatric symptoms during subsequent treatment and poorer social adjustment.

PMID- 8550953
TI  - GABA and mood disorders: a brief review and hypothesis.
AB  - Considerable evidence implicates the neurotransmitter gamma-aminobutyric acid
      (GABA) in the biochemical pathophysiology of mood disorders. Animal models of
      depression show regional brain GABA deficits and GABA agonists have
      antidepressant activity in these models. Somatic treatments for depression and
      mania upregulate the GABAB receptor, similar to the effect of GABA agonists.
      Clinical data indicate that decreased GABA function accompanies depressed or
      manic mood states. GABA agonists are effective antidepressant and antimanic
      agents. Low GABA levels are found in brain, cerebrospinal fluid and plasma of
      patients with depression and in plasma of patients with mania. Plasma GABA
      levels, which reflect brain GABA, are not normalized with treatment and clinical
      remission in depression, suggesting low GABA is not a marker for mood state. Some
      somatic treatments, including valproic acid and electroconvulsive shock, reduced
      plasma GABA and response to these correlates with higher levels of baseline
      plasma GABA. From these data, a GABA hypothesis for mood disorders is formulated.
      Low GABA function is proposed to be an inherited biological marker of
      vulnerability for development of mood disorders. Environmental factors, including
      stress and excessive alcohol use, may increase GABA, causing symptoms of
      depression or mania. Treatment, or the passage of time, then returns GABA to its
      presymptomatic baseline as the symptoms remit. This hypothesis, applicable to a
      subset of mood disordered persons, is testable.

PMID- 8550954
TI  - Contrasting neuroendocrine responses in depression and chronic fatigue syndrome.
AB  - Hypothalamic-pituitary-adrenal (HPA) axis and central 5-HT function were compared
      in chronic fatigue syndrome (CFS), depression and healthy states. 10 patients
      with CFS and 15 patients with major depression were matched for age, weight, sex
      and menstrual cycle with 25 healthy controls. Baseline-circulating cortisol
      levels were highest in the depressed, lowest in the CFS and intermediate between
      the two in the control group (P = 0.01). Prolactin responses to the selective 5
      HT-releasing agent d-fenfluramine were lowest in the depressed, highest in the
      CFS and intermediate between both in the healthy group (P = 0.01). Matched pair
      analysis confirmed higher prolactin responses in CFS patients than controls (P =
      0.05) and lower responses in depressed patients than controls (P = 0.003). There
      were strong inverse correlations between prolactin and cortisol responses and
      baseline cortisol values. These data confirm that depression is associated with
      hypercotisolaemia and reduced central 5-HT neurotransmission and suggest that CFS
      may be associated with hypocortisolaemia and increased 5-HT function. The
      opposing responses in CFS and depression may be related to reversed patterns of
      behavioural dysfunction seen in these conditions. These findings attest to
      biological distinctions between these disorders.

PMID- 8550955
TI  - An augmented escape of androstenedione from suppression by dexamethasone in
      melancholia: relationships to intact ACTH and cortisol nonsuppression.
AB  - To further examine the association between basal and postdexamethasone (DST)
      pituitary and adrenal activity in depression, the authors measured intact
      adrenocorticotropic hormone (ACTH), androstenedione and cortisol, both in
      baseline and post-DST conditions, in 63 depressed subjects (14 minor, 33 simple
      major and 16 melancholic subjects). It was found that post-DST androstenedione,
      cortisol and ACTH values were significantly higher in melancholic than in minor
      depressed subjects. There were highly significant correlations between plasma
      androstenedione and ACTH both in baseline and post-DST conditions. The
      significant intercategory differences in post-DST androstenedione were determined
      by differences in post-DST ACTH. Basal and post-DST androstenedione values were
      significantly higher in men than in women and both values were significantly and
      negatively related to age. There were highly significant, positive relationships
      between cortisol and ACTH and between cortisol and androstenedione both in
      baseline and post-DST conditions. The results corroborate our hypotheses that, in
      depression, pituitary (ACTH) and adrenal (cortisol and androstenedione) hormonal
      secretion are tightly coupled in post-DST conditions and that the augmented
      escape of ACTH-target hormones in melancholia is, in part, related to that of
      pituitary ACTH.

PMID- 8550956
TI  - Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble
      interleukin-2 and transferrin receptor in major depression.
AB  - Recently, it was found that major depression may be accompanied by significant
      changes in cell-mediated and humoral immunity. The purpose of this study was to
      investigate the plasma concentrations of interleukin (IL)-6, soluble IL-6
      receptor (sIL-6R), sIL-2R and transferrin receptor (TfR) in patients with major
      depression in an acute phase of illness, in remission and during antidepressive
      treatment. Plasma concentrations of IL-6, sIL-6R, sIL-2R and TfR were
      significantly higher in major depressed subjects than in healthy controls. In
      major depressed subjects, but not in normal controls, there were significant
      positive correlations between the plasma concentrations of IL-6 and sIL-6R, IL-6
      and sIL-2R, IL-6 and TfR, and between sIL-2R and TfR. Subchronic treatment with
      antidepressive drugs, such as fluoxetine or tricyclic antidepressants, did not
      significantly affect plasma IL-6, sIL-6R, sIL-2R or TfR. The latter did not
      significantly differ between major depressed patients in an acute phase of
      illness or in complete clinical remission. It is suggested that: (1) a
      coordinated and upregulated production of IL-6, sIL-6R, sIL-2R and TfR may
      constitute a trait marker of major depression; and that (2) an upregulated
      production of IL-6 may represent a contributing factor to the various immune
      disorders encountered in major depression and maybe to the pathophysiology or
      pathogenesis of that illness.

PMID- 8550957
TI  - Analysis of the terms used by general practitioners to characterize patients
      considered by them as depressed. A prospective study on 682 patients.
AB  - The aim of the study was to investigate the terms used by general practitioners
      (GPs) to describe the patients considered by them to be depressed. 682 patients
      were diagnosed as depressed by 79 GPs selected at random in four regions of
      France. The frequency of the diagnosis of depression made by GPs in the total
      patient population was 3.6-5%. The GPs were asked to describe the main symptoms
      of these patients on a plain chart. The percentage of use of each term was
      calculated in each region. In all the regions, the most frequent symptoms were
      insomnia (31.8%), fatigue (29.9%) and anxiety (24.6%). The results suggest that
      the three main terms used by GPs to describe depression differ from those used by
      psychiatrists.

PMID- 8550958
TI  - The prevalence of depression in a cohort of the very elderly.
AB  - In a community study of 1173 very elderly (> or = 77 years) subjects, a screening
      interview was followed by a CAMDEX diagnostic interview in a subsample of 461.
      The estimated prevalence of DSM-III-R major depressive disorder in the community
      sampled was 2.4% (95% CI 0.9%, 4.0%). Using CAMDEX criteria, the prevalence of
      depressive illness was 3.0% (95% CI 0.7%, 5.3%). 10% of those who had a
      diagnostic interview were rated as having depressive symptoms of mild or moderate
      severity. Of these, approximately 1/3 met diagnostic criteria for major
      depressive disorder. The significance of these findings and the possible need for
      wider criteria for depression in the elderly are discussed.

PMID- 8550959
TI  - American College of Cardiology 45th annual scientific session. Orlando, Florida,
      March 24-27, 1996. Abstracts.

PMID- 8550960
TI  - 52nd Annual meeting of the American Academy of Allergy, Asthma and Immunology
      (AAAAI). New Orleans, Louisiana, March 15-20, 1996. Abstracts.

PMID- 8550961
TI  - From strategic planning to TQM: a complete management approach.
AB  - Organizations can no longer rely on a single management solution as they respond
      to a complex world. Biomedical communications managers need to employ a variety
      of management tools as they cope with a rapidly changing landscape and an
      increasing set of business pressures. This article describes two management
      strategies, strategic planning and total quality management, which can be used to
      achieve success in the 21st century.

PMID- 8550962
TI  - Production planning for operating room videography.
AB  - Successful video coverage of the surgical event involves careful planning in the
      preproduction stages. Prior knowledge of the intended audience enables the video
      producer to employ the tools and techniques that obtain the most appropriate
      visual perspective of the operative anatomy. Additionally, familiarity with the
      salient steps of the operation allows the production team to anticipate the moves
      of the surgical staff, so that important events are not missed. The video crew
      must also evaluate the operating room environment and the traffic patterns of the
      surgical team, so that there is no compromise to the quality of patient care.

PMID- 8550963
TI  - The Internet and World Wide Web explained.
AB  - Most people have by now heard of the Internet. Its presence is advertised via
      newspapers, magazines, television and radio. The Internet offers exciting new
      opportunities for information exchange and medical photographers and illustrators
      should be exploiting the potential of these services. This article seeks to
      explain what the Internet is and how the World Wide Web makes access to the
      Internet comparatively simple. It also attempts to demystify the jargon and
      explain how you can connect to the services on offer.

PMID- 8550964
TI  - Design standards for computer-generated teaching slides.
AB  - This article looks at the increasing use of the computer-generated teaching slide
      in a large teaching hospital, where the medical illustration department provides
      a bureau service for output. Lack of understanding by clients of basic design
      principles can present a number of problems. A study was undertaken on the slide
      making habits of professional healthcare educators and, from the information
      gathered, common problems were identified and a multifaceted approach to
      improving the design capability of clients was adopted.

PMID- 8550965
TI  - Design for slides.
AB  - The basic principles of design for projection slides are discussed, with
      particular reference to the impact of the personal computer and commercial
      presentation software on the material that is destined to end up on the screen at
      meetings and in seminar rooms. While modern software can be a boon to the
      presenter, allowing simple creation of slides, it can also encourage some of the
      worst excesses. The keynote of the design of slides for educational purposes
      should be simplicity, and ways of achieving simple but effective results are
      described.

PMID- 8550966
TI  - [Consensus Conference on Induced Labor. Paris, November 29-30, 1995].

PMID- 8550967
TI  - [Recommendations for clinical practice or consensus conferences?].

PMID- 8550968
TI  - [Advantages and disadvantages of induced labor without medical indication: the
      viewpoint of the epidemiologist].

PMID- 8550969
TI  - [Induced labor without medical indications: the viewpoint of women. Bibliographic
      review].

PMID- 8550970
TI  - [What are the medico-legal implications of induced labor?].

PMID- 8550971
TI  - [Induced labor by pharmacological methods. Advantages and disadvantages].

PMID- 8550972
TI  - [Strategies for induction of labor].

PMID- 8550973
TI  - [Indications for pregnancy termination in cases of pre-eclampsia, hypertension,
      intrauterine growth retardation, liver and heart disease].

PMID- 8550974
TI  - [What is the role of induced delivery in France and the world?].

PMID- 8550975
TI  - [Is induced labor justified in diabetes, macrosomia and prolonged pregnancy?].

PMID- 8550976
TI  - [Induced delivery in premature rupture of membranes].

PMID- 8550977
TI  - [Induced delivery in fetal malformations].

PMID- 8550978
TI  - [Is induced labor justified in cases of scarred uterus, breech presentation and
      multiple pregnancy?].

PMID- 8550979
TI  - [The epidemiologists' point of view on medical indications for induced labor].

PMID- 8550980
TI  - [Advantages and disadvantages of induced labor without medical indications: the
      viewpoint of the obstetrician in hospital practice].

PMID- 8550981
TI  - [Advantages and disadvantages of induced labor without medical indication: the
      viewpoint of obstetricians in private practice].

PMID- 8550982
TI  - [Induced labor by mechanical methods. Advantages and disadvantages].

PMID- 8550983
TI  - [Advantages and disadvantages of induced labor without medical indications: the
      viewpoint of the midwife].

PMID- 8550984
TI  - [Advantages and disadvantages of induced labor without medical indications: the
      viewpoint of the pediatrician].

PMID- 8550985
TI  - [Advantages and disadvantages of induced labor without medical indications: the
      viewpoint of the anesthesiologist].

PMID- 8550986
TI  - Acute sporadic hepatitis E virus infection in southern China.
AB  - BACKGROUND/AIMS: The hepatitis E virus is responsible for epidemic and sporadic
      hepatitis in northwestern China, but its role as a cause of acute sporadic
      hepatitis in southern China has not been reported. METHODS: We applied the most
      practical current methods for diagnosis of hepatitis E virus infection, IgM and
      IgG anti-HEV detection by enzyme linked immunosorbent assay, to investigate the
      prevalence of hepatitis E virus infection among acute sporadic hepatitis.
      RESULTS: Anti-HEV IgM was found in 1 of 26 (3.8%), 4 of 20 (20.0%), 4 of 19
      (21.1%), and 51 of 142 (35.9%), with acute hepatitis A, B, C and non-ABC,
      respectively. Anti-HEV IgM was not detectable in healthy subjects, while IgG anti
      HEV was found in 14 of 77 healthy subjects (18.2%) and was long-lasting. Ninety
      one cases without any evidence of hepatitis A, B or C infections and anti-HEV IgM
      were tentatively classified as non-A, B, C, D, E (non-ABCDE) hepatitis. By
      comparison with non-ABCDE, cases with hepatitis E were more frequently icteric
      and exhibited higher alanine aminotransferase levels (92.2% vs. 45.1%, 770 iu/l
      vs 377 iu/l, respectively, p < 0.005). Chronic cases were not observed in
      hepatitis E virus infections. However, 14 of 91 (15.4%) cases with non-ABCDE
      developed to chronicity (p < 0.005). CONCLUSIONS: Hepatitis E virus infection is
      sporadic as well as endemic in southern China. Only IgM anti-HEV but not IgG anti
      HEV can be used as an appropriate marker of acute hepatitis E virus infection.
      Superinfection of hepatitis E virus with other types of hepatitis viruses is
      frequent in this area. While the disease was associated with more severe clinical
      manifestations, patients usually recovered completely.

PMID- 8550987
TI  - Comparative analysis of two assays for genotyping hepatitis C virus based on
      genotype-specific primers or probes.
AB  - BACKGROUND/AIMS: The importance of determining the hepatitis C virus genotype has
      increased since several authors have described a good correlation between
      hepatitis C virus genotype and response to interferon treatment or to disease
      severity. It is thus of particular importance to develop reliable assays for
      hepatitis C virus genotyping. METHODS: We have comparatively analyzed hepatitis C
      virus genotypes of 208 French and Italian chronically infected patients using
      genotype-specific primers polymerase chain reaction in the capsid region and a
      genotype-specific probe-based assay in the 5' untranslated region (LiPA).
      RESULTS: We found a good concordance between the two assays for the prevalent
      genotypes in our regions (145/174). The nucleotide sequences in the 5'UTR and
      capsid domain were investigated to determine the molecular basis of some
      discordant results. This analysis showed that the genotype-specific probe-based
      assay gave more consistent results, probably because this technique is based on
      several probes distributed along the 5'UTR to reveal each genotype. In contrast,
      the low variability of 5'UTR did not always permit classification of the
      hepatitis C virus genotype 1 subtypes. We also found some problems, using
      genotype-specific primers polymerase chain reaction, for less represented
      genotypes; in particular, in the presence of type 2a/III we obtained more
      discordant results. This observation is of importance in view of the potential
      association of this genotype with mild liver disease and a good response to
      interferon-a treatment.

PMID- 8550988
TI  - The effect of nitric oxide synthase inhibition on portal pressure and azygos
      blood flow in patients with cirrhosis.
AB  - It has been proposed that the hyperdynamic circulation found in cirrhosis is
      mediated by nitric oxide released through the induction of nitric oxide synthase.
      To investigate this the effect of the nitric oxide synthase inhibitor, NG
      monomethyl-L-arginine (L-NMMA), was studied upon the portal circulation. After a
      30-min infusion of 3 mg/kg of L-NMMA there was a significant fall in heart rate
      from 83.2 +/- 4.4 to 74.2 +/- 3.9 bpm (p = 0.005), and a significant rise in mean
      arterial pressure from 91.6 +/- 2.2 to 103.7 +/- 3.2 mmHg, p = 0.004). There was,
      however, no change in hepatic venous pressure gradient (16.7 +/- 1.5 to 16.1 +/-
      1.7 mmHg, p = 0.477) nor in azygos venous blood flow (366 +/- 126 to 368 +/- 145
      ml/min, p = 0.683). On subgroups analysis by Child-Pugh grade, significant
      changes occurred in heart rate and mean arterial pressure only in grade A and B
      patients (p = 0.0061 and p = 0.0068, respectively). Regional peripheral blood
      flow was studied using hand thermography. All patients who had an isothermic
      hands (relatively cold fingers compared to palmar temperature) at the start of
      the study developed an isothermic pattern after the L-NMMA infusion. This study
      demonstrates a significant systemic effect of nitric oxide synthase inhibition in
      patients with cirrhosis but no effect upon the portal or portosystemic collateral
      circulations at this dose.

PMID- 8550989
TI  - The difference in liver pathology between sporadic and familial forms of
      porphyria cutanea tarda: the role of iron.
AB  - Porphyria cutanea tarda is a disorder of porphyrin metabolism, of which familial
      and sporadic forms have been described. Factors such as iron seem necessary for
      porphyria cutanea tarda to become clinically manifest. To study the relationship
      between iron and uroporphyrins in hepatocytes of patients with porphyria cutanea
      tarda, a morphological and morphometrical study was performed in 13 liver
      biopsies of patients with porphyria cutanea tarda (eight with sporadic porphyria
      cutanea tarda and five with familial porphyria cutanea tarda). In addition,
      possible differences in clinical and biochemical features and in
      histopathological findings between patients with sporadic porphyria cutanea tarda
      and familial porphyria cutanea tarda were investigated. Familial porphyria
      cutanea tarda patients presented at a younger age than sporadic porphyria cutanea
      tarda patients (42.4 +/- 5.3 vs. 57.3 +/- 8.6 years). Biochemical features were
      not different between sporadic porphyria cutanea tarda and familial porphyria
      cutanea tarda patients. Uroporphyrin crystals and a variable degree of liver
      siderosis were detected in the biopsies of all 13 patients. Uroporphyrin crystals
      were often found close to ferritin-like iron deposits. The morphometrical
      analysis showed that an increased mean area fraction of ferritin iron was
      associated with an increased mean area fraction of uroporphyrin crystals in
      hepatocytes of sporadic porphyria cutanea tarda and familial porphyria cutanea
      tarda patients. Moreover, the amount of uroporphyrin crystals was significantly
      higher in livers of familial porphyria cutanea tarda than sporadic porphyria
      cutanea tarda patients. These findings are consistent with the hypothesis that
      uroporphyria is precipitated by an iron-dependent process.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8550990
TI  - Phenocopies of poor metabolizers of omeprazole caused by liver disease and drug
      treatment.
AB  - BACKGROUND/AIMS: The kinetics of omeprazole and its primary metabolites 5'
      hydroxyomeprazole and omeprazole sulfone were studied in healthy volunteers to
      evaluate omeprazole as a probe drug for the S-mephenytoin hydroxylase (CYP2C19)
      polymorphism. The plasma metabolic ratio obtained from the concentrations of
      omeprazole plus omeprazole sulfone over 5'-hydroxyomeprazole was investigated.
      METHODS: The time course of the omeprazole metabolic ratio was studied in 14
      extensive metabolizers, one intermediate, and five poor metabolizers of CYP2C19
      after a 1-week administration of 40 mg/d omeprazole. The ratio was then
      determined in 187 randomly selected Caucasian hospital patients and analyzed
      according to liver disease and co-medication. RESULTS: Between 1 and 4 h after
      omeprazole intake, the volunteers phenotyped by the urinary S/R-mephenytoin ratio
      were reliably identified as extensive metabolizers and poor metabolizers by an
      omeprazole metabolic ratio-antimode of 12. This antimode remained valid in eight
      extensive metabolizers and one poor metabolizer, who were re-investigated with 60
      mg omeprazole b.i.d. for one week. Among 30 patients without concomitant drug
      intake, only one poor metabolizer (3.3%) was identified by both the S/R
      mephenytoin ratio and omeprazole metabolic ratio. However, 30 of 47 patients with
      liver disease and 20 of 110 co-medicated patients without liver disease had a
      ratio > 12. This highly exceeded the poor metabolizer frequency of 3-4% in
      Caucasians. CONCLUSIONS: Like other phenotypic tests, the omeprazole metabolic
      ratio appears to reflect CYP2C19 genotype reliably only in individuals without
      liver disease or co-medication. The omeprazole metabolic ratio may serve the
      double purpose of phenotyping for CYP2C19 and to individualize dosing in
      omeprazole-treated patients.

PMID- 8550991
TI  - Focal destructive cholangiopathy associated with amoxycillin/clavulanic acid
      (Augmentin).
AB  - Amoxycillin/clavulanic acid (Augmentin) has been widely used as a broad spectrum
      antibiotic since its introduction in 1981, since which time a number of reports
      of adverse hepatic reaction to the drug combination have been published. This
      paper describes five patients presenting with cholestatic illness within 8 weeks
      of a course of amoxycillin/clavulanic acid. The clinical picture indicated a
      direct link between the illness and the drug combination. Hepatic histology
      revealed a distinctive focal destructive cholangiopathy in all five patients,
      which has not previously been reported. Two also showed a granulomatous reaction,
      which has only previously been reported in one patient. Parallels are drawn with
      other diseases displaying bile duct destruction, and it is suggested that
      immunologically mediated drug-induced biliary damage may be involved. One of the
      five patients developed chronic liver disease with persistence of cholestatic
      liver biochemical tests, which has not previously been reported. The severity of
      the reaction and its prolonged course merit wider recognition of the possible
      adverse hepatic reaction to amoxycillin/clavulanic acid.

PMID- 8550992
TI  - Biliary secretion of bile acids and lipids in primary sclerosing cholangitis.
      Influence of cholestasis and effect of ursodeoxycholic acid treatment.
AB  - In patients with primary sclerosing cholangitis cholestasis is a prominent
      feature of the disease. We studied the effect of cholestasis and of
      ursodeoxycholic acid treatment on the biliary secretion of bile acids and lipids
      in ten patients with primary sclerosing cholangitis. Ursodeoxycholic acid
      treatment for 3 months led to an increase in the biliary secretion rates of total
      bile acids from 0.91 mmol/h to 1.47 mmol/h, mainly due to an increase in
      urosodeoxycholic acid, which represented 31% of biliary bile acids. With
      increasing cholestasis, the biliary enrichment of the bile acid pool with
      urosodeoxycholic acid decreased. Biliary output of endogenous bile acids on
      average was unchanged, but in patients with cholestasis and diminished output
      before treatment, it increased after ursodeoxycholic acid. Phospholipid secretion
      increased from 0.26 mmol/h to 0.43 mmol/h without correlation to the degree of
      cholestasis. Biliary cholesterol secretion on average was unchanged after
      ursodeoxycholic acid (0.1 versus 0.09 mmol/h) but, in patients with cholestasis
      and diminished output before treatment, it increased after ursodeoxycholic acid.
      The decreasing enrichment of the bile acid pool with ursodeoxycholic acid with
      increasing cholestasis may be related to its slight effect in advanced disease.
      The increase in biliary phospholipid secretion may represent another mechanism of
      action of urosodeoxycholic acid responsible for its beneficial effect in
      cholestatic liver disease.

PMID- 8550993
TI  - Mitochondrial respiratory chain defect: a new etiology for neonatal cholestasis
      and early liver insufficiency.
AB  - Two siblings presented with neonatal cholestasis and early liver insufficiency.
      The older was admitted for end-stage cirrhosis with severe hypoglycemia and had
      long-term successful liver transplant at the age of 15 months. The second child
      presented a similar neonatal history of cholestasis, hypoglycemia,
      hyperlactacidemia, liver insufficiency and progressive cirrhosis. Extensive work
      up excluded all known causes of neonatal cholestasis. Gluconeogenesis was found
      normal following alanine and fructose infusion. Repeated hypoglycemia with early
      post-prandial hyperlactacidemia led us to investigate the mitochondrial
      respiratory chain enzyme activities. Selective defects of complexes I, III and
      IV, coded by mitochondrial DNA, were detected in liver tissue of this patient and
      on preserved frozen tissue from his sibling, whilst normal activities were found
      in liver tissue samples from control patients with end-stage liver diseases. No
      extrahepatic manifestations were found. We conclude that liver deficiency of
      mitochondrial respiratory chain enzymes may cause liver disease in neonates,
      associated with hypoglycemia and post-prandial hyperlactacidemia. The disease is
      cured by liver transplantation.

PMID- 8550994
TI  - Interleukin-6 production by human liver (myo)fibroblasts in culture. Evidence for
      a regulatory role of LPS, IL-1 beta and TNF alpha.
AB  - BACKGROUND/AIMS: Interleukin-6 is a major trigger for the synthesis of acute
      phase proteins by liver parenchymal cells. Acute phase proteins may contribute to
      the regulation of liver fibrosis by inhibition of proteases (e.g. collagenase)
      and by binding of cytokines. Since liver (myo)fibroblasts play an important role
      in the production of extracellular matrix in fibrotic livers, a study was
      undertaken into whether these cells are able to synthesize interleukin-6, which
      would give them the opportunity to contribute to regulation of synthesis of acute
      phase proteins by neighbouring parenchymal cells. METHODS: In the present study
      we investigated interleukin-6 production by two cell types obtained from human
      liver tissue: human fat-storing cells obtained from 5-15% Percoll fractions,
      which transformed in culture into myofibroblasts co-expressing alpha-smooth
      muscle actin and vimentin (VA cells) and fibroblasts obtained from 30-40% Percoll
      fractions which express vimentin only (V vells). Interleukin-6 production was
      measured in culture media of these cells using an enzyme-linked immunosorbent
      assay after incubation with lipopolysaccharide, and mediators like interleukin-1
      beta, tumor necrosis factor-alpha, transforming growth factor-beta and interferon
      gamma, known to be present in elevated concentrations in fibrotic livers.
      RESULTS: Unstimulated human liver (myo)fibroblasts produced considerable amounts
      of interleukin-6 (287 ng/mg cellular protein (VA cells), and 54 ng/mg cellular
      protein (V cells), within 48 h). Biological activity of these high concentrations
      of interleukin-6 measured in the enzyme-linked immuno-sorbent assay was confirmed
      in the B9-bioassay for interleukin-6 and by stimulation of alpha 2-macroglobulin
      production in rat liver parenchymal cell cultures. Lipopolysaccharide,
      interleukin-1 beta and tumor necrosis factor-alpha were potent stimulators of
      basal interleukin-6 production by VA and V cells, 1 microgram/ml
      lipopolysaccharide enhanced basal interleukin-6 production 3-fold within 48 h.
      100 U/ml interleukin-1 beta and 1000 U/ml tumor necrosis factor-alpha each
      stimulated basal interleukin-6 production by VA cells 2-5 fold, whereas V cells
      were stimulated 10-25 fold. These effects were specific since the stimulation by
      lipopolysaccharide was completely inhibited by polymyxin B and the enhancing
      effects of interleukin-1 beta and tumor necrosis factor-alpha were neutralized by
      specific antibodies. Transforming growth factor-beta and interferon gamma did not
      influence interleukin-6 synthesis by either cell type in culture. CONCLUSIONS:
      These results indicate that transformed fat-storing cells (VA cells) and
      fibroblasts (V cells) may function as a local source of interleukin-6 in the
      human liver. Since interleukin-6 plays a key role in the regulation of the
      production of acute phase proteins by liver parenchymal cells, we hypothesize
      that human liver (myo)fibroblasts may stimulate local production of acute phase
      proteins in the fibrotic liver, thus contributing to local regulation of
      inflammatory and fibrogenic reactions.

PMID- 8550995
TI  - Collagen synthesis by human liver (myo)fibroblasts in culture: evidence for a
      regulatory role of IL-1 beta, IL-4, TGF beta and IFN gamma.
AB  - BACKGROUND/AIMS: Different cytokines have been described in fibrotic livers,
      including interleukin-1, interleukin-4 and interferon gamma, which are capable of
      regulating collagen production in human skin and lung fibroblasts. METHODS: To
      investigate possible involvement of interleukin-1, interleukin-4 and interferon
      gamma in the regulation of collagen production in human liver fibrosis, we
      studied the effects of these cytokines on collagen synthesis by nonparenchymal
      human liver cells in vitro. The effects of interleukin-1, interleukin-4 and
      interferon gamma were compared with the effect of transforming growth factor
      beta, a well-known stimulator of collagen synthesis in liver fibrosis. Using a
      Percoll gradient we isolated two types of fibroblast-like cells from human liver
      tissue: fat-storing cells, which transformed in culture into myofibroblasts co
      expressing vimentin and alpha-smooth muscle actin (VA-cells), and fibroblasts
      expressing vimentin only (V-cells). Production of collagen was measured in
      confluent cell cultures by incorporation of 3H-proline into collagenase
      degradable proteins. RESULTS: The cytokines studied had comparable effects on
      collagen synthesis in confluent cultures of VA-cells obtained from three
      different human livers and in confluent cultures of V-cells. Interleukin-1 beta
      and interleukin-4 enhanced collagen synthesis dose-dependently. 100 U/ml
      interleukin-1 beta stimulated collagen synthesis up to 174 +/- 25% (mean +/- sd,
      VA-cells) and 140 +/- 7% (V-cells) of control values. 1000 U/ml interleukin-4
      enhanced collagen formation up to 195 +/- 58% (mean +/- sd, VA-cells) and 153 +/-
      4% (V-cells) of control values after 48 h. These values were comparable to the
      stimulatory effects induced by transforming growth factor-beta (235 +/- 33% (mean
      +/- sd, VA-cells) and 150 +/- 18% of control values (V-cells) after incubation
      with 10 ng/ml transforming growth factor-beta for 48 h). Interferon gamma reduced
      both basal (36 +/- 29% (mean +/- sd) of control values in VA-cells, and 59 +/- 9%
      in V-cells) and transforming growth factor-beta induced collagen synthesis.
      CONCLUSIONS: These results indicate that in addition to the well-known role of
      transformed fat-storing cells (VA-cells) in collagen synthesis, fibroblasts (V
      cells) may contribute to collagen production in human liver tissue. Moreover,
      these data demonstrate that in addition to the extensively documented collagen
      inducing mediator transforming growth factor-beta, other cytokines present in
      fibrotic liver tissue like interleukin-1 beta and interleukin-4 may contribute to
      the enhanced synthesis of collagen, whereas interferon gamma may reduce collagen
      formation during liver fibrosis in man.

PMID- 8550996
TI  - Acinar and cellular distribution and mRNA expression of the epidermal growth
      factor receptor are changed during liver regeneration.
AB  - The epidermal growth factor receptor shows acinar heterogeneity with a portal-to
      central concentration gradient. Immunohistochemical analysis showed that the
      strong cytoplasmic staining for epidermal growth factor receptor found in normal
      hepatocytes disappears over time after partial hepatectomy or sham operation,
      however, with different time courses. Four hours after surgery, 84.3 +/- 3.5%
      (mean +/- SD) of the hepatocytes in animals after sham operation showed strong
      cytoplasmic staining vs. 21.8 +/- 19.0% in animals after partial hepatectomy.
      After 12 h, the cytoplasmic staining in animals after sham operation was further
      reduced to 39.0 +/- 22.6% vs. 20.0 +/- 5.5% in animals after partial hepatectomy.
      At the same time point, we found staining for the epidermal growth factor
      receptor in nuclei of 21.8 +/- 14.8% and 3.0 +/- 3.9% of the hepatocytes in
      animals after partial hepatectomy and animals after sham operation, respectively.
      Northern blot analysis revealed comparable changes in expression of the epidermal
      growth factor receptor mRNA in animals after partial hepatectomy and in animals
      after sham operation. No changes were evident in animals after sham operation,
      however, if the abdominal incisions were shortened. This suggests that at least
      part of the changes found in animals with sham operation are due to acute phase
      events and/or surgical stress. In conclusion, partial hepatectomy induces changes
      in the intracellular and acinar fate of the epidermal growth factor receptor,
      drives the receptor to the nuclei, and affects the expression of the epidermal
      growth factor receptor mRNA.

PMID- 8550997
TI  - Basic fibroblast growth factor is hepatotropic for rat liver in regeneration.
AB  - A role for fibroblast growth factor in liver regeneration has recently been
      suggested. In this study we followed the intravenous delivery of recombinant
      human [125I]basic fibroblast growth factor to the liver of rats following 68%
      partial hepatectomy. The concentration of [125I]basic fibroblast growth factor
      was higher in the liver (mean +/- SD, 6.8 +/- 0.89% of injected dose) and the
      kidney (6.7 +/- 0.2%) of sham-operated rats than in the spleen (2.8 +/- 0.45%).
      It increased threefold in the liver only, soon after 68% partial hepatectomy
      (20.3 +/- 5.3%, p < 0.001), and remained high for the first 24 h. We also studied
      the effect of basic fibroblast growth factor injection on the rate of
      [3H]thymidine incorporation into liver DNA in rats subjected to either 21% or 68%
      partial hepatectomy. A significant increase was seen after intramesenteric
      injection of 500 ng basic fibroblast growth factor into rats subjected to 21%
      partial hepatectomy (23.5 +/- 7.3 cpm/micrograms DNA) compared to saline-injected
      rats (14.5 +/- 6.4 cpm/micrograms DNA, p = 0.034). A dose of 5000-25,000 ng
      injected into a peripheral vein resulted in higher thymidine incorporation than
      in saline-injected control rats (36.9 +/- 12.7 and 9.7 +/- 6.1 cpm/micrograms
      DNA, respectively; p < 0.0001). No significant effect was seen after 68% partial
      hepatectomy. Autoradiography showed that the hepatocytes were the predominant
      labelled cells early after hepatectomy and basic fibroblast growth factor
      injection. We conclude that basic fibroblast growth factor uptake by the liver is
      increased after 68% partial hepatectomy and that basic fibroblast growth factor
      is mitogenic to liver parenchymal cells early after 21% partial hepatectomy.

PMID- 8550998
TI  - In vivo amino acid fluxes in regenerating liver after two-thirds hepatectomy in
      the rat.
AB  - BACKGROUND/AIMS: Recent reports in the literature suggest that liver cell
      swelling following amino acid influx exerts anabolic and anti-catabolic effects.
      We have tested the possibility that rapid liver growth after partial hepatectomy
      is promoted by an increased amino acid-influx and that this is associated with an
      increased hepatic water content and a decreased rate of proteolysis. METHODS: Two
      thirds hepatectomy was performed in rats. Plasma liver flow and amino acid fluxes
      were measured after 24 or 48 h. RESULTS: Plasma liver flow was increased 24 and
      48 h after partial hepatectomy or sham-operation in pair-fed animals. At these
      time points, in both groups there was a specific two- to threefold increased net
      hepatic uptake of the amino acids alanine and glycine, both being transported by
      the sodium-coupled amino acid transport system A/ASC. No changes in uptake of
      system N transported amino acids were observed. Both in partially hepatectomized
      and sham-operated pair-fed animals, the hepatic uptake of alanine and glycine was
      accompanied by a minor increase in tissue water (from 68 to 70%). Proteolysis,
      measured by leucine efflux, was only reduced in regenerating livers. CONCLUSIONS:
      We conclude that cell swelling is not an important factor in the stimulation of
      net protein synthesis during liver regeneration.

PMID- 8550999
TI  - The role of increased nitric oxide in the vascular hyporeactivity to
      noradrenaline in long-term portal vein ligated rats.
AB  - To test the possible role of nitric oxide production in long-term portal vein
      ligation in the rat, where the hyperdynamic circulation was reported to be
      absent, in vivo experiments on isolated thoracic aortic rings from partial portal
      vein ligated or sham-operated rats were performed, 6 months postoperatively. The
      concentration-response curves to noradrenaline of both intact and endothelium
      denuded rings from portal hypertensive rats were significantly shifted to the
      right as compared to those from sham-operated animals. In intact rings, addition
      of NG-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, resulted
      in a significant shift of the curves to the left in sham-operated and portal vein
      ligated rats. In endothelium-denuded rings, addition of NG-nitro-L-arginine
      resulted in a significant shift of the curves to the left in portal vein ligated
      but not in sham-operated animals. After blockade of the nitric oxide biosynthesis
      with NG-nitro-L-arginine, the negative logarithm of the concentration of
      nonadrenaline causing half-maximal response did not significantly differ any more
      between portal vein ligated and sham-operated rats; in endothelium-denuded rings
      hyporeactivity to noradrenaline persisted in portal vein ligated rats. Only in
      the intact rings did NG-nitro-L-arginine significantly increase the maximal
      contractions. No differences were demonstrated in endothelium-dependent
      relaxations to acetylcholine between sham-operated and portal hypertensive
      animals. From these results, it can be concluded that in vitro aortic
      hyporeactivity to noradrenaline is still present in long-term portal vein ligated
      rats, and that it results at least partially from activation of the L-arginine:
      nitric oxide pathway in the aortic vascular wall.

PMID- 8551000
TI  - Fulminant hepatitis due to Epstein-Barr virus infection.
AB  - Epstein-Barr virus infection is a benign disease, which may occasionally be
      fatal, particularly in children. Epstein-Barr virus infection is rare in elderly
      subjects and appears to have a self-limited course. An unusual case of fulminant
      hepatitis due to primary Epstein-Barr virus infection in a 62-year-old male 18
      days after a cardiosurgical operation and blood transfusions is described in the
      present paper. Post-mortem examination of the liver showed massive hepatic
      necrosis. The etiology was established by increase in IgM antibodies to Epstein
      Barr virus (titer 1:3.120) in serum and by cellular expression of Epstein-Barr
      virus DNA in liver tissue.

PMID- 8551001
TI  - Azathioprine-induced myelosuppression due to thiopurine methyltransferase
      deficiency in a patient with autoimmune hepatitis.
AB  - Azathioprine can cause severe myelosuppression. The inherited activity of the
      enzyme thiopurine methyltransferase has been recently recognised as a major
      factor in the susceptibility to myelosuppression. Thiopurine methyltransferase
      deficiency occurs at a frequency of one in 300 and is associated with profound
      myelosuppression after a short course of azathioprine. Very low thiopurine
      methyltransferase activity represents the TPMTL/TPMTL genotype, and can be
      detected before therapy with azathioprine is started. We describe the first
      documented case of azathioprine-induced severe myelosuppression due to thiopurine
      methyltransferase deficiency in autoimmune liver disease. The azathioprine dose
      was low (1 mg/kg) and pancytopenia occurred after 56 days therapy. It would be
      advisable to measure thiopurine methyltransferase activity before patients with
      autoimmune hepatitis are exposed to azathioprine.

PMID- 8551002
TI  - Nitric oxide and portal hypertension.

PMID- 8551003
TI  - Are asymptomatic blood donors with indeterminate results on RIBA 3 really able to
      transmit HCV infection?

PMID- 8551004
TI  - Association of splenic vein obstruction and coeliac disease in an Indian patient.

PMID- 8551005
TI  - Detection of hepatitis B virus markers in corneal buttons.

PMID- 8551006
TI  - Adjuvant therapy for interferon-resistant patients: do cyclooxygenase inhibitors
      have any role? A pilot study.

PMID- 8551007
TI  - Role of reactive metabolites in drug-induced hepatitis.

PMID- 8551008
TI  - Cirrhosis: ascites and hepatorenal syndrome. Recent advances in pathogenesis.

PMID- 8551009
TI  - Malnutrition in cirrhosis.

PMID- 8551010
TI  - Portal hypertension: diagnosis and treatment.

PMID- 8551011
TI  - Current concepts in diagnosis and therapy of pediatric liver diseases.

PMID- 8551012
TI  - Histopathological diagnosis and terminology of chronic hepatitis.

PMID- 8551013
TI  - Liver allograft rejection--current concepts on diagnosis and treatment.

PMID- 8551014
TI  - Alcoholic liver disease: pathobiological aspects.

PMID- 8551015
TI  - On the early history of male hysteria and psychic trauma. Charcot's influence on
      Freudian thought.
AB  - This paper discusses the influence of Jean-Martin Charcot's views on Sigmund
      Freud's early theory of hysteria and the notion of psychical trauma. We consider
      the early history of both psychical trauma and male hysteria, for in Charcot's
      view traumatic hysteria and male hysteria are identical. Freud's two 1886
      lectures on male hysteria, delivered after his return from Paris, are crucial to
      the subject because they present Freud's first impressions of Charcot and his
      teaching. Some of the ideas presented in the two lectures foreshadow Freud's
      later generalization of the etiological role of trauma and his theory of the role
      of psychical trauma in the genesis of hysteria; that is, each hysterical symptom
      is due to a psychical trauma reviving an earlier traumatic event--the so-called
      principle of deferred action (Nachtraglichkeit). Several arguments substantiate
      the thesis that Freud's notion of psychical (sexual) trauma was developed in
      reference to Charcot's notion of traumatic hysteria, and that the early
      psychoanalytic theory of psychical trauma is clearly indebted to Freud's
      encounter with Charcot's male traumatic hysterical patients. The discussed
      Freudian development points out the major role of (physical) traumata in
      eliciting psychopathological pictures and in this way is of definite historical
      relevance for the present-day discussion on the traumatic nature of the so-called
      multiple personality syndrome and other dissociative disorders, and post
      traumatic stress disorders.

PMID- 8551016
TI  - Bacterial contaminated breast milk and necrotizing enterocolitis in preterm
      twins.
AB  - A pair of preterm twins developed fatal necrotizing enterocolitis (NEC) in
      association with Staphylococcus epidermidis septicaemia after receiving
      contaminated expressed breast milk (EBM). S. epidermidis NEC can be associated
      with severe bowel inflammation, high morbidity and mortality. Breast milk is the
      most suitable nutrient for preterm infants but EBM should undergo regular
      screening for bacterial overgrowth. We urge caution before administering EBM
      found to be heavily contaminated with S. epidermidis to preterm infants.

PMID- 8551018
TI  - Epidemiological analysis of strains of methicillin-resistant Staphylococcus
      aureus (MRSA) infection in the nursery; prognosis of MRSA carrier infants.
AB  - Forty-five neonates who carried methicillin-resistant Staphylococcus aureus
      (MRSA) were studied. Retrospective molecular analysis using pulsed-field gel
      electrophoresis showed three separate MRSA epidemics in the nursery. Strains of
      MRSA isolated from the neonates were also isolated from the hospital environment
      and health care providers. Clinical manifestations included skin pustules (eight
      patients), conjunctivitis (four patients), or other minor infections (two
      patients). No neonate developed systemic infection. The prevalence of MRSA
      decreased with age. At one year, three (14.3%) of 21 infants that had carried
      MRSA at six days remained carriers and only two (1.1%) of 180 infants in a
      control 'S. aureus-negative at six days' group carried MRSA.

PMID- 8551017
TI  - Molecular epidemiology of Staphylococcus epidermidis blood isolates from neonatal
      intensive care unit patients.
AB  - Twelve episodes of Staphylococcus epidermidis bacteraemia occurred within three
      months in a neonatal intensive care unit. Plasmid profiles and Southern blot
      hybridization with five different probes were used to determine whether an
      endemic strain of S. epidermidis could be identified among the contemporary
      isolates. It was concluded that this methodology was satisfactory for
      differentiation between isolates of coagulase-negative staphylococci: fifteen
      isolates were divided in eight groups indicating that there was no single endemic
      strain causing the outbreak.

PMID- 8551019
TI  - Labile antibiotic resistance in Staphylococcus aureus.
AB  - Twenty-two isolates of Staphylococcus aureus, recovered from patients over a
      period of about one year, exhibited low level resistance to mupirocin, developed
      a salmon pink colour on culture and 21 had the same phage-type. However the
      plasmid profiles and associated antibiotic resistances differed. Digestion of
      cellular DNA with SmaI showed that two isolates from a single patient had a
      markedly different pattern to the remainder, and that six others differed by one
      band, though these formed groups of one and five isolates. This episode
      apparently represents a small outbreak of colonization or infection, which would
      have been missed but for the unusual pigmentation of the isolates recovered, and
      illustrates the difficulties of relying on a single typing system.

PMID- 8551020
TI  - Occupational risk of hepatitis B and C infections in Saudi medical staff.
AB  - The prevalence of markers for hepatitis B virus (HBV) and hepatitis C virus (HCV)
      was studied among final year medical students and the medical staff at two
      university teaching hospitals in Saudi Arabia. At King Khalid University Hospital
      (KKUH) in Riyadh, evidence of exposure to HBV in the male medical staff (42.9%)
      was significantly greater than among medical students (25.3% males, 19.3%
      females; P = 0.0041) or the controls (28.6% males, 17.1% females; P = 0.0095). At
      King Fahad University Hospital (KFUH) in Al-Khobar, although the prevalence of
      exposure in the medical staff (28.3%) was higher than that in the controls
      (18.5%) the difference was not statistically significant (P > 0.05) and this
      could be due to the small numbers tested (46 physicians, 54 controls). Regarding
      exposure to HCV there was no significant difference in markers of the virus among
      the three categories investigated (1.7% in the controls, 2.6% in medical students
      and 1.9% in the medical staff). The low risk of transmission in the medical staff
      could be due to the small amount of the virus in the blood of HCV carriers. It
      can be concluded from the study that, in contrast to HCV, the occupational risk
      of HBV infection is high among Saudi physicians and hence HBV vaccination to
      unexposed medical staff is the only way for effective prevention of infection.

PMID- 8551021
TI  - An analysis of the trends in the use of antifungal drugs and fungal isolates in a
      UK University Hospital.

PMID- 8551022
TI  - Quality of water in washer-disinfectors.

PMID- 8551023
TI  - Theatre air and operating conditions.

PMID- 8551024
TI  - Guidelines for the establishment and operation of human milk banks in the UK.

PMID- 8551025
TI  - The Lowbury Lecture. The economics of nosocomial infections.
AB  - A simple model of the costs and benefits of an infection control programme is
      presented. Liberal costs and conservative benefits were assumed. The concepts of
      crude and attributable mortality were applied to examine the cost per life year
      saved if a minority of infection-related deaths were prevented. An effective
      infection control programme is one of the most cost-beneficial medical
      interventions available in modern public health.

PMID- 8551026
TI  - Decreased transmission of Enterobacteriaceae with extended-spectrum beta
      lactamases in an intensive care unit by nursing reorganization.
AB  - In our gastrointestinal surgical intensive care unit (SICU), the large number of
      patients with multiple enterostomies enhances the risk of nosocomial transmission
      of gut extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) by
      health care workers. A control study performed in our SICU from June-August 1992
      showed an ESBLE gut colonization rate of 70%. To reduce this rate, nursing
      procedures were intensified or modified, particularly handwashing, single-use
      equipment and waste control. To test the efficiency of these procedures, 64
      patients hospitalized for more than two days from September 1992-March 1993 were
      screened for gut acquisition of ESBLE. Rectal samples were taken within 48 h
      after admission and then weekly. After nursing reorganization, the ESBLE
      colonization rate dropped significantly to 40% (P < 0.001). Twenty patients
      (31.7%) acquired a gut ESBLE, after a mean of 24.3 +/- 13.7 days. Each patient
      was colonized with one, two or three ESBLE (Klebsiella pneumoniae, Escherichia
      coli and Enterobacter aerogenes). Baseline characteristics of the 20 colonized
      and 39 non-colonized patients showed no significant difference (Student's t-test,
      P > 0.05). The nursing workload, estimated as a omega index, was greater in the
      colonized group (P < 0.001). These findings show that strict observance of
      nursing procedures can significantly reduce ESBLE acquisition in a high-risk
      surgical unit.

PMID- 8551027
TI  - Pyrolysis mass spectrometry of cephalosporin-resistant Enterobacter cloacae.
AB  - Thirteen clinical and four environmental isolates of third-generation
      cephalosporin-resistant Enterobacter cloacae (CREC) together with single isolates
      from the hands of a nurse and from a blood gas analyser were associated with two
      clusters of nosocomial infection. With an unrelated CREC isolate they had been
      typed by serotype, biotype, ribotype and phage-type and were examined by
      pyrolysis mass spectrometry (PYMS) as described here. PYMS data yielded two
      clusters, major and minor. All except one isolate in the major cluster
      corresponded to type group identity (serotype 07, biotype 62, ribotype D) which
      had caused neonatal sepsis and colonization. Multivariate analysis showed a
      homogeneous group consisting of this strain plus two outliers. The minor cluster
      included four different strains, one of which, serotype 03, biotype 62, ribotype
      C had caused excoriation of the buttocks and colonization.

PMID- 8551028
TI  - Cleavable CD40Ig fusion proteins and the binding to sgp39.
AB  - Recombinant immunoglobulin (Ig) fusion proteins of cell surface and intracellular
      proteins have wide applications. For example, fusion proteins have been used in
      the isolation, identification and study of ligands and the effects of binding or
      blocking a receptor-ligand pair, either in vivo or in vitro. For some
      applications, removal of the immunoglobulin Fc region is advantageous. We have
      developed two vectors for the expression of Ig fusion proteins that contain
      recognition sequences for protease cleavage using thrombin. In one vector, the
      sequence encoding the thrombin cleavage site is located at the junction of the
      DNA fragment encoding the protein or protein fragment to be studied and the hinge
      and constant regions of the immunoglobulin, allowing the generation of a
      monomeric form of the protein of interest. In the second vector, the sequence
      encoding the thrombin cleavage site is located between the sequences encoding the
      hinge and constant regions of the immunoglobulin, allowing for the generation of
      covalent dimers of the recombinant protein without the constant Fc domains. We
      have used these vectors to produce the constructs encoding two forms of the
      extracellular domain of CD40, CD40ThrIg and CD40HinThrIg, allowing production of
      a monomeric and dimeric form of recombinant CD40. Cleavage is efficient and
      complete. Following cleavage, there was no detectable binding of the monomeric
      form of CD40 to a soluble form of gp39, the ligand of CD40, while the dimeric
      form was able to bind. These vectors have been constructed to allow facile
      substitution with other sequences to generate cleavable forms of other proteins
      of interest.

PMID- 8551029
TI  - Detection of intracytoplasmic cytokine using flow cytometry and directly
      conjugated anti-cytokine antibodies.
AB  - Recently, there have been several reports demonstrating improvements in the flow
      cytometric detection of intracellular cytokines. These advances, although
      significant, have not yielded techniques that have easily been translated into
      broad use. To address this issue, we have coupled a fixation and permeabilization
      method with the use of directly labelled monoclonal anti-cytokine antibodies,
      providing both improved signal and simpler staining. The kinetics of in situ
      cytokine production in both CD4 and CD8 cells are shown for IL-2, IL-4, IL-5 and
      IFN-gamma. Based on these data, 6 h was chosen for optimal detection of this
      combination of cytokines. We show the specificity of this technique by blocking
      cytokine staining using a molar excess of recombinant cytokine. Additionally,
      unlabelled anti-cytokine antibodies are demonstrated to block specific staining
      of labelled antibody, providing an objective means to place statistical markers.
      Using such controls, we routinely detected as few as 0.1% false positive cells,
      allowing the flow cytometric detection of IL-5, which is below the threshold of
      detection of published methods. To further prove the specificity of staining, we
      stained using two anti-IL-5 mAbs known to recognize different epitopes and
      demonstrate that the same cells stain with both antibodies. Without
      permeabilization we could detect a fraction of cells with low intensity staining
      for cytokine. This staining was further examined using differential two color
      staining for intracellular and extracellular cytokine, clearly demonstrating no
      cells staining exclusively for extracellular cytokine, confirming a lack of
      passive transfer of cytokine to nearby cells. We show that cytokine flow
      cytometry is useful in examining the increased IL-5 production characteristic of
      eosinophilic states and that IL-5 production is limited to the CD27 negative
      subpopulation. These data illustrate the unique capability of cytokine flow
      cytometry to correlate cytokine expression with cell surface phenotype without
      cell separation. In summary, using directly conjugated anti-cytokine antibodies,
      cytokine flow cytometry becomes a specific and versatile technique for the
      assessment of complex cytokine production phenotypes in fresh ex vivo T cell
      subpopulations.

PMID- 8551030
TI  - Influence of specimen age and anticoagulant on flow cytometric evaluation of
      granulocyte oxidative burst generation.
AB  - The oxidative burst generation capacity of granulocytes can be reliably detected
      by a flow cytometric procedure using lysed whole blood, dihydrorhodamine 123
      (DHR), and phorbol myristate acetate (PMA). This assay is used to detect chronic
      granulomatous disease (CGD) and the CGD carrier state. To assess the feasibility
      of performing this assay in a reference laboratory setting, we investigated the
      influence of anticoagulant and specimen age on flow cytometric detection of
      granulocyte oxidative burst generation. Peripheral blood from 20 healthy controls
      was collected in acid citrate dextrose (ACD), ethylenediaminetetraacetate (EDTA),
      or sodium heparin (HEP) and held at room temperature. At 4, 24, 48, 72, and 96 h
      after collection, red cells were lysed, the white cells loaded with DHR, and then
      activated by PMA. Granulocyte-associated fluorescence, indicative of oxidative
      burst generation, was assessed by flow cytometry. Blood in any of the three
      anticoagulants tested gave reliable results (> 90% of granulocytes positive for
      fluorescence) at 4 h after collection; at 24 h after collection, HEP and ACD
      specimens performed slightly better than EDTA specimens. At later time points,
      HEP proved superior to ACD and EDTA for maintaining granulocyte oxidative burst
      capacity. As a demonstration of the practical utility of the assay, both CGD and
      the CGD carrier state were accurately detected using heparinized blood specimens
      analyzed 72 h after collection. These results show that heparinized blood
      specimens up to 72 h old can be used to reliably assess granulocyte oxidative
      burst generation.

PMID- 8551031
TI  - Stable transfection of cloned murine T helper cells.
AB  - Here we describe a protocol for the stable transfection of murine T helper (Th)
      cells and long term culture of the resulting transfectants. The electroporation
      protocol was established for the murine Th2 clone L1/1 by testing different
      parameters determining the electric field (capacitance, voltage, single or twin
      pulse) as well as the activation status of the cells. The transfected T cells
      were genetically altered by stable integration of the neomycin resistance gene,
      encoded in the vector pM5neo, into the genome. For selection and long term
      culture of stable transfectants a scheme combining selection with the antibiotic
      neomycin (G-418, Geneticin) and repeated stimulation with antigen presenting
      cells (APC) and antigen was established. This protocol should also be applicable
      to other antigen reactive T cells. The resistance of the T cells to neomycin
      correlated directly with expression of the transferred neomycin resistance gene
      as demonstrated by mRNA analysis. Applying periodic reselection with neomycin the
      transfected Th2 cells were found to be stable for more than 18 months in culture
      and displayed an unaltered antigen recognition and lymphokine production pattern
      as compared with the untransfected L1/1 Th2 cells.

PMID- 8551032
TI  - Internalization of human macrophage surface antigens induced by monoclonal
      antibodies.
AB  - Drugs intended to be endocytosed by macrophages may be transported by MAbs
      directed against these cells. Twenty MAbs were investigated for this purpose. The
      binding of these MAbs to macrophages obtained from a 7 day culture of blood
      monocytes showed that anti-CD11b and anti-CD14 recognized the highest number of
      cell surface antigen sites. Further assays determined that anti-CD63, Mo5 and
      anti-CD33 were the MAbs that induced the strongest modulation of the
      corresponding antigens, the highest rate being with anti-CD63. Endocytosis of
      antigen-antibody complexes was evidenced by the presence of MAbs in the
      cytoplasm. Anti-CD63 MAbs induced the highest internalization in this assay. For
      most MAbs, however, the density of antigen sites and the intensity of antigen
      modulation were not predictive of the amount of MAb detected in the cytoplasm.

PMID- 8551033
TI  - Purification and immunocharacterization of human brain glutamine synthetase and
      its detection in cerebrospinal fluid and serum by a sandwich enzyme immunoassay.
AB  - A modified procedure employing a single chromatographic step to purify glutamine
      synthetase from human brain is described. The enzyme was characterized by native,
      denaturing, and two-dimensional gel electrophoresis and immunoblotting. Yield and
      purity were assessed by enzyme activity assay and a newly developed sandwich
      enzyme immunoassay using a mouse monoclonal antibody against native sheep brain
      glutamine synthetase. The immunoassay detected glutamine synthetase protein in
      samples where the enzyme had been inactivated by repeated cycles of freezing and
      thawing, and in serum and cerebrospinal fluid where glutamine synthetase was
      undetectable by the enzyme activity assay. Native glutamine synthetase from human
      brain occurred as an octamer with an estimated molecular weight of 360-400 kDa.
      Under reducing and denaturing conditions, the enzyme dissociated into monomeric
      subunits with an estimated molecular weight of 44 kDa. The monomers were
      recognized by the monoclonal antibody on immunoblots but not in the sandwich
      enzyme immunoassay, suggesting that the antigenic site occurs once on each
      subunit. Both human and sheep brain glutamine synthetases were composed of three
      and four different types of subunits with isoelectric points ranging from 7.0-7.2
      and 6.8-7.0, respectively.

PMID- 8551034
TI  - Establishment of dengue virus-specific human CD4+ T lymphocyte clones from
      Percoll-purified T lymphoblasts by stimulation with monoclonal antibody to CD3.

PMID- 8551035
TI  - Major histocompatibility complex class I binding glycopeptides for the estimation
      of 'empty' class I molecules.
AB  - Different forms of major histocompatibility complex (MHC) class I heavy chains
      are known to be expressed on the cell surface, including molecules which are
      functionally 'empty'. Direct peptide binding to cells is obvious during
      sensitization of target cells in vitro for cytotoxic T lymphocyte killing and
      'empty' MHC-I molecules are comparatively abundant on TAP-1/2 peptide transporter
      mutant cells. In the present work we have estimated the fraction of 'empty' MHC
      class I molecules using glycosylated peptides and cellular staining with
      carbohydrate specific monoclonal antibodies. Synthetic Db and Kb binding peptides
      were coupled at different positions with different di- or trisaccharides, using
      different spacing between the carbohydrate and the peptide backbone. Binding of
      sugar specific mAbs was compared in ELISA and cellular assays. An optimal Db
      binding glycopeptide was used for comparative staining with anti-Db and anti
      carbohydrate monoclonal antibodies to estimate fractions of 'empty' molecules on
      different T lymphoid cells. On activated normal T cells, a large fraction of Db
      molecules were found to be 'empty'. The functional role of such 'empty' MHC class
      I molecules on T cells is presently unclear. However, on antigen presenting cells
      they might participate in the antigen presentation process.

PMID- 8551036
TI  - Quantification of natural antibody producing B cells in rats by an improved
      ELISPOT technique using the polyvinylidene difluoride membrane as the solid
      support.
AB  - We describe here a new type of solid support for the ELISPOT assay, the PVDF
      membrane. In parallel tests, spot yields on this membrane were superior to those
      obtained with the frequently used nitrocellulose (NC) membrane, coated with the
      same rat anti-IgM and anti-IgG antibodies, incubated with the same rat spleen
      cell suspensions, and developed with the same combination of AP-labeled
      conjugates and substrate. We therefore used the PVDF membrane, coated with anti
      rat IgM and IgG antibodies, ssDNA or bromelain-treated mouse erythrocytes
      (BrMRBC) (exposing phosphatidylcholine (PC) as major autoantigen) to develop
      ELISPOT assays for the quantification of isotype-specific natural antibody
      secreting cells (ASC) in rats. We confirmed the isotype specificity of the
      binding of the anti-rat IgM and anti-rat IgG coating antibodies and conjugates
      with the secreted rat antibodies in this assay, and, by inhibition of spot
      formation with soluble antigen, their specificity for ssDNA and BrMRBC. An in
      house 18-well culture device for the easy manufacture of PVDF-lined culture wells
      greatly facilitated coating, blocking, and washing procedures, as compared to the
      original method in 24 well culture plates. This simple, fast, specific and
      sensitive ELISPOT assay was used to make an inventory of the numbers of natural
      splenic ASC in Wistar and Fischer rats.

PMID- 8551037
TI  - Mouse ear spleen grafts: a model for intrasplenic immunization with minute
      amounts of antigen.
AB  - The production of monoclonal antibodies to protein antigens which can only be
      obtained in tiny amounts has been a major task, since classical in vivo
      immunization procedures are not always efficient. In order to circumvent this
      problem, two methods have been developed: (1) in vitro immunization, in which the
      immunogen is presented directly to spleen cell cultures; (2) intrasplenic
      immunization, a technique in which the immunogen is deposited in the spleen
      tissue. The latter approach requires less laboratory work and the risk of
      contamination, often a problem with in vitro cultures (Nilsson and Larsson,
      Immunol. Today (1990) 11, 10), is greatly reduced. Here, we describe a novel
      method of grafting neonatal spleens in the pinna of the mouse ear. Histological
      and functional studies show that these spleen grafts have white and red pulp and
      contain normal percentages of functional T and B cells. The results indicate that
      this procedure is extremely efficient in priming mice for a secondary humoral
      immune response, since very small amounts of soluble antigen (ovalbumin) were
      required. The data are discussed in terms of the advantages of this new technique
      over current procedures for intrasplenic immunization.

PMID- 8551038
TI  - Generation of type VIII collagen-specific antibodies.
AB  - We generated a specific polyclonal antibody against the alpha 1 chain of type
      VIII collagen. The antibody detects type VIII collagen and is definitely free of
      crossreactivities with the closely related type X collagen. The antibody was
      generated against a dodecamer peptide chosen to satisfy the following
      requirements: (a) maximal homology between collagen type VIII molecules from
      different species; (b) maximal antigenicity as predicted by algorithms from Emini
      et al. (J. Virol. (1985) 55, 836). Hoop and Woods (Proc. Natl. Acad. Sci. USA
      (1981) 78, 3824), and Karplus and Schulz (Naturwissenschaften (1985) 72, 212);
      and (c) maximal specificity, i.e. absence of this sequence in all other proteins
      known so far. All three requirements were satisfied for a sequence fragment of 12
      amino acids (100-111) in the alpha 1(VIII) NC2 domain. This peptide was produced
      synthetically. Polyclonal antibodies were raised in rabbits and affinity purified
      on a peptide column. The antibody was tested in a quantitative EIA, immunoblots
      and in immunocytochemistry and found to be well-suited for all three types of
      application. The antibody did not crossreact with type X collagen and other
      extracellular matrix molecules in the EIA. In immunoblots of affinity-purified
      extracts of the Descemet membrane, a major source of type VIII collagen, the
      antibody detected several known forms of type VIII collagen. In
      immunocytochemistry the antibody stained endothelial and astrocytoma cells in
      monolayer cultures, and cells and extracellular matrix in cryosections of the
      human Ewing sarcoma, arterial vessels and chicken embryonic heart, whereas the
      chicken tibiotarsus remained negative. This distribution of immunoreactivity
      corresponds to the distribution of type VIII but not that of type X collagen. In
      conclusion this antibody may serve as a highly specific and sensitive tool for
      investigating the appearance and regulation of type VIII collagen.

PMID- 8551039
TI  - Binding of autoreactive mouse anti-type II collagen antibodies derived from the
      primary and the secondary immune response investigated with the biosensor
      technique.
AB  - The reactivity of autoantibodies to type II collagen, secreted by B cells
      isolated from the primary and the secondary immune response to rat type II
      collagen in DBA/1 mice, was investigated using BIAcore 2000 instrumentation.
      Assays were performed on both collagen and antibody surfaces. These assays
      demonstrated a 100-fold difference in affinity between primary and secondary
      immune response antibodies. The difference in affinity was almost entirely due to
      differences in the dissociation rate constant. Somatic mutations in secondary
      clones were in one case associated with a 3-4-fold difference in affinity and in
      another case appeared to be without any effect on the binding activity.

PMID- 8551040
TI  - Production and characterization of a monoclonal antibody against Schistosoma
      japonicum glutathione S-transferase.
AB  - Schistosoma japonicum glutathione S-transferase (GST), expressed from a pGEX
      plasmid, was isolated from Escherichia coli cells and used to immunize mice in
      order to generate specific anti-GST monoclonal antibodies. Using a modified
      immunization and fusion procedure, one stable hybridoma clone secreting an anti
      GST antibody (alpha GST-1) was obtained. Milligram quantities of this antibody
      were produced in vitro in a miniPERM bioreactor and subsequently purified by
      protein G affinity chromatography. The characteristics of this antibody were
      investigated by enzyme-linked immunosorbent assays and immunoblotting
      experiments. The alpha GST-1 antibody was found to react specifically with GST
      and GST fusion proteins and demonstrated no reactivity with normal E. coli
      proteins. This monoclonal antibody should be a valuable reagent for tracing the
      production of GST fusion proteins and possibly for affinity purification of GST
      fusion proteins.

PMID- 8551041
TI  - Carboxyfluorescein diacetate labeling does not affect adhesion molecule
      expression or function in human neutrophils or eosinophils.
AB  - Fluorescently labeled leukocytes are commonly used in in vitro and in vivo
      experimental systems. However, the effects of fluorescent labeling on the
      expression and function of leukocyte adhesion molecules has not been examined in
      part because the extreme intensity of fluorescence tends to obscure signals from
      other fluorochromes used for dual color analysis. We have utilized a novel
      technique involving a 7-amino-4-methylcoumarin-3-acetic acid (AMCA) fluorophore
      conjugated F(ab')2 fragment excitable in the ultraviolet wavelength range (350
      450 nm) and dual-laser flow cytometry to determine if labeling of human
      neutrophils and eosinophils with the fluorescent dye 5-(6)-carboxyfluorescein
      diacetate (CFDA) alters surface expression of the primary leukocyte adhesion
      molecules involved in leukocyte-endothelial interactions. Simultaneously,
      adhesion molecule function was assessed by comparing the ability of CFDA-labeled
      vs. control cells to adhere to cultured human umbilical vein endothelial cells
      (HUVEC) and purified immobilized adhesion molecules. Isolated human eosinophils
      and neutrophils were fluorescently labeled by incubation with CFDA. Flow
      cytometric comparisons of labeled and unlabeled cells demonstrated that
      fluorescence labeling of neutrophils and eosinophils with CFDA did not alter
      basal surface expression of the beta 2 integrins (i.e., CD11a CD11b or, CD18).
      Stimulation of neutrophils with fMLP and eosinophils with PMA resulted in
      increased surface expression of CD11b and CD18 which was not altered by CFDA
      labeling. Likewise, CFDA labeling of neutrophils and eosinophils did not
      significantly alter their integrin-dependent adhesion to activated HUVEC under
      static or rotational conditions. Similarly, adhesion to immobilized recombinant E
      and P-selectin was unaltered. These data demonstrate that fluorescent labeling
      of human neutrophils and eosinophils with CFDA does not alter surface expression
      or function of several adhesion molecules necessary for leukocyte-endothelial
      interactions. The use of CFDA-labeled cells in experiments employing intravital
      microscopy should therefore provide valid information on adhesion molecule
      function in vivo.

PMID- 8551042
TI  - Solid phase synthesis of bifunctional antibodies.
AB  - Bifunctional antibodies were prepared using the principle of solid-phase
      synthesis. The two Fab' fragments were chemically linked together via a
      bismaleimide crosslinking reagent. The F(ab')2 fragments from intact IgG were
      prepared using an immobilized pepsin column. Goat, mouse and human antibodies
      were digested completely within 4 h. The F(ab')2 fragments thus produced did not
      contain any IgG impurities. The Fab' fragments were produced by reducing the
      inter-heavy chain disulfide bonds using 2-mercaptoethylamine. The use of the
      solid-phase reactor in the preparation of the bifunctional antibodies eliminated
      many of the time-consuming separation steps between the fragmentation and
      conjugation steps. This procedure facilitates the automation of the bifunctional
      antibody preparation and the rapid optimization of reaction conditions.

PMID- 8551043
TI  - Detection of secreted and intracellular annexin II by a radioimmunoassay.
AB  - A simple radioimmunoassay for detection of secreted and intracellular annexin II
      in human cells is presented. Annexin II is a multifunctional protein in human
      cells and may have a role in several types of cancers. No enzymatic activity has
      been associated with the protein, thus making its detection difficult. Using
      purified annexin II from human placenta, we have developed a sensitive
      radioimmunoassay protocol. A linear response was observed up to a concentration
      of 0.5 microgram purified protein in the assay. Using this radioimmunoassay
      protocol, annexin II can be detected in undiluted clinical human samples such as
      bronchoalveolar lavages and various tissue extracts. We demonstrate the
      applicability of this technique to measure intracellular annexin II in extracts
      of a human adenocarcinoma cell line (HeLa) and secreted annexin II from
      bronchoalveolar lavage fluid from a human patient. Using HeLa cell extracts and
      BAL, we observed a linear response with up to 10 micrograms total protein in the
      assay. We further demonstrate the applicability of this technique to measure
      differences in intracellular and secreted annexin II in the human pancreatic
      adenocarcinoma cell lines CD-11, CD-18 and Capan-2. While CD-11 and CD-18 do not
      secrete annexin II, the cell line Capan-2 secretes high levels of the protein.

PMID- 8551044
TI  - Characterization of transendothelial chemotaxis of T lymphocytes.
AB  - We have adapted a chemotaxis assay using human umbilical vein endothelial cell
      (HUVEC) monolayers on microporous membranes for studying lymphocyte
      transendothelial chemotaxis in vitro. Supernatants of peripheral blood
      mononuclear cells stimulated with phytohemagglutinin (PHA) were identified as an
      excellent source of lymphocyte chemoattractant activity. The activity in PHA
      supernatant typically caused 2-6% of peripheral blood lymphocytes (PBL) to
      transmigrate compared to 0.1-0.3% to media control. Checkerboard analysis
      demonstrated that transmigration was directional and not attributable to random
      locomotion. Purified T lymphocytes also underwent transendothelial chemotaxis to
      PHA supernatant. Using monoclonal antibodies to several human adhesion receptors,
      we found that the interaction between LFA-1 and ICAM-1/ICAM-2 was more important
      for transendothelial lymphocyte chemotaxis than the interaction between VLA-4 and
      VCAM-1. A monoclonal antibody to the beta 1 integrin subunit inhibited chemotaxis
      more than antibodies to the VLA alpha 2, alpha 3, alpha 4, or alpha 5 subunits.
      The transendothelial assay was used to guide purification of the lymphocyte
      chemoattractant activity, which we reported previously to be monocyte
      chemoattractant protein-1 (MCP-1) (Carr et al., Proc. Natl. Acad. Sci. USA (1994)
      91, 3652). The adhesion molecules required for chemotaxis to MCP-1 were similar
      to those with PHA supernatant. The use of HUVEC in the assay enhances the signal
      to-background ratio of chemotaxis and provides a model that is physiologically
      relevant to lymphocyte emigration from the bloodstream into sites of
      inflammation.

PMID- 8551045
TI  - Anti-Thomsen-Friedenreich (T) antibody and its application to human breast
      carcinoma: where are we after 20 years?

PMID- 8551046
TI  - Anti-Thomsen-Friedenreich (T) antibody-based ELISA and its application to human
      breast carcinoma detection.
AB  - An anti-Thomsen-Friedenreich (T) antibody-based enzyme-linked immunosorbent assay
      (ELISA) with high efficacy in human breast carcinoma detection is described.
      Immunoreactive T epitopes occur in approximately 90% of all carcinomata; all
      humans have anti-T antibodies, naturally occurring anti-carcinoma antibodies,
      induced by their own intestinal flora. Carcinoma patients, but not control
      subjects, show alterations of serum anti-T hemagglutinin levels. Human anti-T
      antibodies are predominantly IgM. In the protocol presented here, anti-T IgM
      antibodies are quantitated by ELISA using Immulon 2 wells coated with human blood
      group O erythrocyte-derived T antigen as solid phase; in addition, total IgM in
      each serum is quantitated by ELISA in parallel with the anti-T IgM. Inter-assay
      coefficient of variation was 2% for both ELISAs. Although anti-T IgM values alone
      distinguish between carcinoma patients and control subjects, use of the quotient,
      QMe, which also considers total IgM, increases this distinction. For a given
      serum, QMe was obtained by the formula: QMe = (100 x (anti-T IgM)2/total IgM).
      Sera of 242 subjects, 117 breast carcinoma patients, 36 benign breast disease
      patients and 89 healthy persons were analyzed. QMe identified 88% of the breast
      carcinoma patients: it all six (100%) in situ, 11/13 (85%) Stage I, 48/58 (83%)
      Stage II and III and 38/40 (95%) Stage IV patients. Sera from 83% of the 36
      benign breast disease patients were negative, i.e. within normal range; five of
      the six positive sera originated from patients with increased long-term risk of
      breast carcinoma, while sera from 11 other patients with increased carcinoma risk
      were negative. Overall, 90% of the 125 non-carcinoma control subjects were
      negative by both anti-T IgM and QMe. In preliminary studies, the ELISA protocol
      detected 11/14 (79%) patients with carcinomata other than those of the breast.
      The identification of all six in situ breast carcinoma patients by QMe points to
      its usefulness in carcinoma detection, especially early.

PMID- 8551047
TI  - Detection of intracellular HIV-1 Rev protein by flow cytometry.
AB  - The Rev trans-activator protein plays a pivotal role in human immunodeficiency
      virus type 1 (HIV-1) replication by allowing expression of the viral structural
      proteins. We have developed a protocol to quantitatively assay intracellular
      steady state levels of Rev Ag (Rev wild type and RevM10 proteins) by flow
      cytometry. Three fixation and permeabilization techniques were compared. These
      protocols varied in the magnitude of the signal which could be detected, and in
      the ability to distinguish between Rev Ag positive and negative populations. This
      technology is applicable to a variety transduced or transfected cell types
      (species, lineage), and for cell lines and primary cells acutely infected with
      HIV-1. The assay is therefore a valuable tool both to analyze Rev protein
      expression levels in HIV-infected cells and to optimize delivery of the dominant
      negative RevM10 gene for clinical gene therapy applications. In addition, a
      second, independent intracellular protein (HIV-Tat) has been detected using the
      same approach.

PMID- 8551048
TI  - Direct calibration ELISA: a rapid method for the simplified determination of
      association constants of unlabeled biological molecules.
AB  - We present a novel method for the rapid determination of association constants.
      The method is based on the direct calibration of an enzyme-linked immunosorbent
      assay (dcELISA) and does not require any external calibration. It combines
      kinetic and equilibrium binding experiments and can be performed on a single
      microtiter plate. The absorbance data are evaluated by several linearized plots
      without the need for sophisticated computations. The dcELISA has been used to
      analyze the binding of a monoclonal antibody, OKT9, to its cognate antigen, the
      human transferrin receptor, and yielded an association constant of Ka = 2.2 x
      10(9) l/mol and a complex formation rate constant of kc = 2.7 x 10(-4) s-1. A 26%
      larger association constant was obtained with a radioimmunoassay (RIA)-based
      Scatchard analysis using 125I-labeled OKT9. By quantifying the binding of the
      same iodinated antibody with the dcELISA we were able to verify that the
      iodination modifies the binding properties of the antibody. The dcELISA thus
      appears to be superior to all methods requiring covalent modifications. In
      principle, the direct calibration method can also be combined with all other
      solid phase assays. It should thus expand their scope in quantifying the binding
      properties of biologically important molecules.

PMID- 8551049
TI  - Mammalian cell fusion in an electroporation device.
AB  - We and others have been interested in the phenomenon of gene 'extinction' in
      somatic cell hybrids, reasoning that the study of this process is likely to
      reveal underlying mechanisms responsible for limiting the expression of
      specialized genes only to appropriate cell types. In the course of our studies in
      this area, we have developed a simple and economical method of fusing mammalian
      cells, using an electroporation device. In fusions between murine myeloma and T
      lymphoma lines, hybrid cell recoveries were typically one per 10(5) [corrected]
      input myeloma cells. Because of our interest in the regulation of immunoglobulin
      heavy chain (IgH) gene expression, we analyzed the hybrids for both IgH gene
      composition and expression. The hybrid lines were phenotypically
      indistinguishable from those generated by the more conventional, polyethylene
      glycol (PEG)-induced fusion protocol. There was a notable increase, however, in
      the number of hybrids that retained IgH-encoding chromosomes from both parental
      lines.

PMID- 8551050
TI  - A simplified method for the coordinate examination of apoptosis and surface
      phenotype of murine lymphocytes.
AB  - Murine lymphocytes readily undergo spontaneous and glucocortocoid-induced
      apoptosis in vitro. It has been previously demonstrated that during apoptosis,
      many cell types including lymphocytes, enzymatically cleave their DNA, thus
      demonstrating a sub-G0 DNA peak when stained with propidium iodide and analyzed
      by flow cytometry. In a mixed population, it is often desirable to phenotypically
      identify distinct populations or subsets undergoing apoptosis, thus requiring
      multiparameter analysis of surface phenotype and DNA content. Paraformaldehyde
      fixation procedures, although common for surface evaluation, have not been
      extensively used in methods quantifying apoptosis. To measure apoptosis in a
      mixed lymphocyte population, we evaluated a gentle detergent permeabilization and
      paraformaldehyde fixation procedure combined with propidium iodide (PI) DNA
      staining, adapted from existing methods for cell cycle studies. With this method
      and rigorous gating techniques which we defined, we detected both apoptotic and
      debris fractions within the sub-G0 cell cycle region of a glucocortocoid-treated
      murine lymphocyte cell line. Using this cell line, WEHI 231.7, as a lymphocyte
      model, we developed a logical gating strategy to exclude debris from analysis. We
      further demonstrated that apoptosis in freshly isolated murine lymphocytes
      detected with paraformaldehyde fixation and PI staining was quantitatively
      comparable to PI staining with ethanol fixation, or nick translation labeling of
      DNA strand breaks (TUNEL). Finally, using fresh murine spleen cells, we
      demonstrated that paraformaldehyde fixation preserves surface protein staining,
      allowing multiparameter analysis of immunophenotype and apoptotic or cell cycle
      status in a mixed lymphocyte population. Thus, this method offers an inexpensive
      and technically simple alternative for assessing apoptosis and surface phenotype.

PMID- 8551051
TI  - A new method for the determination of the ABO blood type of semen by
      immunoblotting using anti-ABH antibodies following immunoprecipitation.
AB  - A new method that enables the ABO blood type of semen to be determined by
      identifying the molecular weight of a blood group substance (BGS) has been
      developed. In order to produce an antibody against a BGS (p84) detected on the
      sperm plasma membrand (SPM), p84 was purified from seminal plasma, injected into
      a rabbit. When seminal plasma was immunoprecipitated with the anti-p84 antibody,
      SDS-PAGE analysis of the immune complex yielded three specific polypeptides with
      molecular masses of 84, 51 and 25 kDa. The first of these polypeptides, p84,
      showed ABH antigenic activity when subjected to immunoblotting. The 51 and 25 kDa
      proteins corresponded to rabbit IgG heavy and light chains, respectively. Using
      this method, ABH antigenic activity of a band with a molecular mass of 84 kDa was
      detected in 25 seminal plasma samples by immunoblotting. When serial two-fold
      dilutions of seminal plasma were analyzed using this method, clear immunoreactive
      84 kDa bands were observed up to 60-fold dilution. When seminal plasma was mixed
      with vaginal fluid at varying ratios, ABH antigenic activity of 84 kDa
      immunoreactive bands could be detected until the seminal plasma: vaginal fluid
      mixture reached a ratio of 1:20. These results suggest that this method will be
      applicable to the analysis of forensic samples of semen contaminated by vaginal
      fluid, such as those obtained from victims of sexual assault.

PMID- 8551052
TI  - Development of a mucosal challenge test for leprosy using leprosin A.
AB  - There is little information about the mucosal immune response in leprosy. We have
      developed a nasal provocation test with leprosin A which will be used to
      investigate mucosal immunity to Mycobacterium leprae. Initial studies were
      performed with increasing doses of leprosin A (1.0 pg/ml-10 micrograms/ml) to
      determine the optimal safe dose of leprosin A. Anti-M. leprae IgA antibody and
      normal IgA concentrations were measured in the saliva of leprosy contacts and
      controls before and after instillation of leprosin A. Nasal leprosin A was well
      tolerated up to a concentration of 10 micrograms/ml without side effects. None of
      the six subjects who had not been exposed to leprosy had salivary IgA against
      whole M. leprae, whereas IgA was detected from 64 h to 140 h following
      instillation of leprosin A in all of the leprosy hospital workers and in 15 out
      of 18 healthy household contacts tested. There was no correlation between serum
      and salivary anti-M. leprae IgA levels before and after testing. Salivary IgA
      anti-lipoarabinomannan responses were seen in 12 out of 20 household contacts.
      Normal salivary IgA concentrations varied from 8 to 240 mg/l. The leprosin A
      nasal provocation test appears to be a safe method for the investigation of the
      role of mucosal immunity in the pathogenesis of leprosy.

PMID- 8551053
TI  - A method for rapid and complete substitution of the circulating erythrocytes in
      SCID mice with bovine erythrocytes and use of the substituted mice for bovine
      hemoprotozoa infections.
AB  - We have previously developed an in vivo experimental system for a bovine
      hemoprotozoan parasite, in which SCID mice were periodically transfused with
      bovine red blood cells (Bo-RBCs), followed by infection with the parasite. The
      SCID mice prepared by the original method, however, had both mouse and bovine
      RBCs in the circulation, and their proportion always fluctuated significantly. In
      the present study, we aimed to deplete the mouse RBCs circulating in SCID mice
      and, thereby, to create SCID mice having complete Bo-RBC substitution. An anti
      erythropoietin rabbit serum, an anti-mouse RBC rabbit serum and 23 monoclonal
      anti-mouse RBC rat antibodies were prepared for this purpose. They were examined,
      after administration into SCID mice, for their ability to decrease hematocrit
      value and also for any other adverse effect. A monoclonal antibody, clone 2E11,
      was found to have potent ability to induce clearance of the mouse RBCs in SCID
      mice without causing toxic effects. SCID mice receiving this antibody together
      with periodic transfusion of Bo-RBCs had their circulating RBCs completely
      substituted with Bo-RBCs. Infection of Bo-RBC-SCID mice with bovine hemoprotozoan
      parasites demonstrated that elimination of the mouse RBCs from Bo-RBC-SCID mice
      resulted in augmentation of parasite growth.

PMID- 8551054
TI  - Immunohistochemical staining of metastatic ductal carcinomas of the breast by
      monoclonal antibodies used in imaging and therapy: A comparative study.
AB  - Five monoclonal antibodies (MoAbs)(L6, 170H.82, 155, BrE-3 and BR96), most of
      which have been previously shown to target breast cancer and not normal tissues
      by immunoscintigraphic imaging, were evaluated for their frequency and pattern
      and immunohistochemical staining in 67 to 116 metastatic lesions from patients
      with ductal carcinoma of the breast. Immunoperoxidase staining in 75% or more of
      the cells occurred in 56/116 (48%) for L6, 44/89 (49%) for Br, -96, 58/102 (57%)
      for 155, 62/99 (84%) for 170H.82, and 65.67 (97%) for BrE-3. With the first three
      MoAbs, an additional 6-10% of the tumors showed staining in 50-75% of tumor
      cells. These results illustrate that most patients with metastatic ductal
      carcinoma have cancer tissue in which a high percent of cells will react to
      several of these selected MoAbs that target different epitopes. The high
      expression of the MoAb targets throughout the tumor tissue makes these antibodies
      potential candidates to carry immunologically directed radioimmunotherapy and is
      an aid in selecting patients for treatment.

PMID- 8551055
TI  - Epidermal growth factor receptor in human breast cancer comparison with steroid
      receptors and other prognostic factors.
AB  - The relationship between epidermal growth factor receptor (EGFR) status and
      various prognostic factors was investigated in 70 human breast cancer specimens.
      Epidermal growth factor receptor was determined by radioligand binding assay,
      standardized by the EORTC Receptor Study Group, using hydroxyapatite to separate
      receptor-bound and free ligand. The percentage of EGFR positivity was 80% when
      the cutoff was set at 5 fmol/mg of membrane protein; this percentage was among
      the highest hitherto reported. Regression analysis of EGFR versus ER and PR
      levels confirmed an inverse relationship between EGFR and ER (p = 0.022) as well
      as between EGFR and PR (p = 0.024). Univariate analysis of the EGFR data
      stratified according to steroid hormone receptor status showed EGFR to be
      negatively associated with ER and PR. No association was found between EGFR and
      menopausal status, axillary lymph node involvement, tumor size, and
      differentiation grade. A direct association between EGFR status and Ki-67
      positive cell rate could be demonstrated.

PMID- 8551056
TI  - Steroid receptors in pleural effusions of advanced breast cancer patients.
AB  - The steroid receptor content in breast carcinoma correlates with the
      responsiveness of malignant cells to endocrine manipulation. Although the steroid
      receptor status of the primary tumor is mostly used to select systemic therapy,
      it was suggested that steroid receptor content should be evaluated in metastatic
      lesions whenever possible. In this study the estrogen and progesterone receptor
      content was determined biochemically in 38 pleural effusions from advanced breast
      cancer patients. In 17/38 patients the steroid receptor status was assessed twice
      during the course of the disease - at diagnosis in the primary tumor/lymph nodes,
      and subsequently in metastatic pleural effusion fluid. A trend towards lower
      receptor values in pleural fluids was evident. There was no correlation between
      pleural steroid receptor content and pleural response to endocrine or
      chemo/endocrine therapy, indicating that the usefulness of effusional steroid
      receptors for therapy planning of advanced breast cancer could not be confirmed
      in this study.

PMID- 8551057
TI  - Clinical utility of hyaluronic acid values in serum and bronchoalveolar lavage
      fluid as tumor marker for bronchogenic carcinoma.
AB  - Various authors have proposed the use of hyaluronic acid (HA) as a tumor marker.
      In order to analyze its usefulness as a marker in bronchogenic carcinoma, the
      most common carcinoma in men, we determined the HA values in serum and
      bronchoalveolar lavage fluid (BAL). We performed prospective studies on two
      groups of patients: 81 diagnosed as having bronchial carcinoma and 34 with benign
      respiratory diseases. HA values were higher in patients with cancer than in those
      with benign diseases (serum: 79.8 ng/ml vs 63.7 ng/ml; BAL: 927 ng/mg vs 522
      ng/mg). Also, the percentage of patients with levels exceeding the established
      cutoff was greater in the group with cancer than in the group with benign disease
      (serum: 24.6 vs 17.6; BAL: 25.3 vs 3). Statistically significant differences in
      these percentages were found in BAL (p<0.01). Patients with extended small cell
      carcinoma had higher HA values (p =0.04) than those with limited disease, and the
      percentage of patients with abnormal HA values was larger in the group with
      extended disease than in the group with limited disease (p = 0.004). The serial
      determinations of HA values in serum reflected the clinical evolution after
      treatment in 73% of the small cell carcinomas. Most of the patients with benign
      diseases whose HA values exceeded the cutoff level suffered from acute infectious
      dis-eases. Once these cases were excluded, the specificity of HA value
      determination in the diagnosis of carcinoma was very high (serum 96%, BAL 100%).
      The determination of HA levels in serum or BAL did not have any prognostic value
      in this study. We conclude that the HA levels in serum and BAL could be of
      interest as a tumor marker, especially in patients with small cell carcinoma.

PMID- 8551058
TI  - Evaluation of the serum markers CEA, NSE, TPS and CYFRA 21.1 in lung cancer.
AB  - We investigated the role of tumor markers CEA, NSE, TPS and CYFRA 21.1 in lung
      cancer diagnosis and staging in 169 patients with histologically confirmed lung
      cancer (43 SCLC and 126 NSCLC). In SCLC patients NSE and CYFRA 21.1 showed the
      highest sensitivity and their combination improve significantly the diagnostic
      sensitivity and accuracy. In NSCLC patients CYFRA 21.1 showed the highest
      sensitivity and global accuracy and no markers association was as effective as
      CYFRA 21.1 alone. Based on data from our study it can be concluded that in
      patients with suspected lung cancer the serum NSE and CYFRA 21.1 assay is a
      suitable association to confirm the clinical hypothesis. NSE in SCLC and CYFRA
      21.1 in NSCLC are useful in the evaluation of disease extent and successive
      treatment planning.

PMID- 8551059
TI  - Determination of tissue polypeptide-specific antigen in pleural fluid and serum
      from patients with pleural effusion.
AB  - As a tool for differentiating malignant and benign pleural effusions, we
      evaluated the diagnostic value of the assay of tissue polypeptide-specific
      antigen (TPS) in pleural fluid and serum, and of the pleural fluid TPS/serum TPS
      ratio in patients with pleural effusion. We studied prospectively 147 consecutive
      patients who had pleural effusions: 43 malignant pleural effusions and 104 benign
      pleural effusions. TPS levels were measured by RIA. The sensitivity and
      specificity of these measurements were: TPS in pleural fluid (cutoff 20,000 U/L):
      0.21 and 0.98; TPS in serum (cutoff 300 U/L); 0.31 and 0.96; pleural fluid
      TPS/serum TPS ratio (cutoff 1200): 0.07 and 0.99. All these values enhanced the
      sensitivity of cytologic analysis of pleural fluid. However, we conclude that TPS
      assay in pleural fluid and serum, and the pleural fluid TPS/serum TPS ratio have
      limited diagnostic value in patients with pleural effusion.

PMID- 8551060
TI  - Development of a new Prolifigen TPA IRMA assay using monoclonal anti-cytokeratin
      antibodies.
AB  - A new immunoassay for TPA determination has been developed in which
      anticytokeratin monoclonal antibodies are used. A three-Mab combination with
      different anticytokeratin antibody specificities has been selected to mimic the
      complex pattern found for the polyclonal anti-TPA antibody. The accuracy of the
      assay is good, as judged from analytical-recovery experiments, analysis of
      quality-assessment samples and comparison with the polyclonal Prolifigen TPA
      IRMA. No significant interferences or cross-reactivities have been identified.
      The lower limit of detection of the assay (mean + 3 SD of the zero standard) is
      below 15 U/L and the imprecision in low, giving a working range of 15-4000 U/L.
      The improved handling of the assay, including a single incubation step of 2 hours
      with shaking at room temperature, results in a narrower normal distribution,
      thereby giving a better separation of normal and pathological samples.

PMID- 8551061
TI  - Evaluation of lipid-bound sialic acid (LSA) as a tumor marker.
AB  - The objective of this study is the evaluation of serum levels of lipid-bound
      sialic acid (LSA) as a of marker cancer. This is a case-control study, and the
      levels of LSA were determined with blinded duplicates of cases and controls.
      Histologic verification of all cancer cases was used to confirm the diagnosis.
      The study included 135 patients with cancer (breast carcinoma, head and neck
      squamous cell carcinoma, lung cancer and gastrointestinal cancer) and 95 controls
      (57 normal subjects and 38 with chronic non-malignant diseases). Marker
      determination was done by the spectrophotometric procedure of Katopodis with
      resorcinol. The mean LSA level in the 57 healthy individuals was 15.09 mg/dl(95%
      C.I., 13.51-16.67), in the entire control group of 95 non-tumoral individuals it
      was 19.21 mg/dl (17.18-21.24), and in the 135 cancer patients it was 26.64 mg/dl
      (24.42-28.87). There was a statistically significant difference between patients
      with chronic non-tumoral diseases and healthy individuals (p < 0.001) and also
      between cancer patients and healthy individuals (p > 0.001), but not between
      cancer patients and patients with chronic non-tumoral diseases (p> 0.05). The
      mean LSA serum values related to tumor site were (mg/dl): breast cancer, 21.49;
      gastrointestinal tumors, 28.45; head and neck cancer, 28.61 and lung cancer,
      32.54. The means according to clinical stage were: complete remission, 18.50
      significantly higher than the healthy controls (p< 0.05); local disease, 23.50 (p
      < 0.01); locoregional disease, (p < 0.05); local disease, 23.50 (p < 0.01);
      locoregional disease, 27.21 (p < 0.001); metastatic disease, 34.49 (p < 0.001),
      and relapses, 20.87 (p< 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8551062
TI  - CA125 Serum levels in tubercolosis patients.

PMID- 8551063
TI  - Reliability of prostate-specific antigen evaluation according to age-specific
      range.

PMID- 8551065
TI  - Stimulation of soluble interleukin-2 release by tumor necrosis factor-alpha in
      cancer patients.

PMID- 8551064
TI  - TPS cytosolic levels in non-malignant breast diseases.

PMID- 8551066
TI  - [Evaluation of surgical procedures based on the types of hypertrophied
      obstructive cardiomyopathy].
AB  - The surgical procedures were reviewed based on the types of hypertrophied
      obstructive cardiomyopathy in 20 patients. The patients were classified in three
      groups: (1) Asymmetric septal hypertrophy (ASH), (2) Atypical or diffuse
      concentric hypertrophy (DIF), (3) Mid ventricular obstructive hypertrophy (MID).
      Among 11 patients with ASH, the ventricular septal myotomy (My) or the myotomy
      myectomy (Mye) were performed in 9 patients and MVR was performed in 2 patients.
      Among 6 patients with DIF, My or Mye were performed in 4 and MVR was performed in
      2. All three patients with MID were treated with MVR. The intraventricular
      systolic pressure gradient greater than 40 mmHg was still existent
      postoperatively in one ASH patient on whom Mye was performed and in 3 DIF
      patients on whom My or Mye were performed. The four patients had III degree
      mitral regurgitation preoperatively and were successfully treated. The
      postoperative NYHA functional class became II or less in all patients. For ASH,
      the My was effective in 9 patients except one earlier patient. For DIF, further
      consideration of surgical procedure might be required. For MID, a MVR is
      recommended.

PMID- 8551067
TI  - [Surgical treatment for Stanford type A acute aortic dissection].
AB  - From March 1983 to September 1994, 53 consecutive patients underwent an emergency
      operation for type A acute aortic dissection. Eighteen patients before 1988
      (Group I) underwent simple ascending aortic replacement (n = 13) and composite
      graft replacement (n = 5) by conventional method. Thirty-five patients after 1989
      (Group II) underwent extended ascending aortic replacement (n = 17), hemiarch
      replacement (n = 6), total arch replacement (n = 8) and composite graft
      replacement (n = 4) using a brief period of circulatory arrest. The overall
      hospital mortality rate was 36.8% in Group I and 25.7% in Group II. The survivals
      after initial operation was 47% at 10 years (Kaplan-Meier) and the event free
      rate was 78% at ten years, respectively. Computed tomographic scanning and
      aortogram demonstrated the patent false lumen in 20 patients (64.5%) at the
      descending thoracic aorta. In conclusion, extended ascending aortic replacement
      is the useful operative technique to perform accurate resection of intimal
      disruption and clamp-site aorta because the replacement of the entry site could
      reduce the risk of operative mortality and reoperation. Total arch replacement is
      not necessarily required, if the entry is properly resected by extended ascending
      aortic replacement or hemiarch replacement. Close follow-up must be considered at
      the patients with patent false lumen, especially in patient with Marfan's
      syndrome.

PMID- 8551068
TI  - [Prolonged preservation due to acceleration of anaerobic glycolysis with
      histidine buffered cardioplegia in canine heart].
AB  - Myocardial preservation has centered around the deep hypothermia with metabolic
      arrest to save energy loss. We evaluated the efficacy of histidine buffered
      cardioplegia containing 100 mM histidine formulated to promote anaeraboic energy
      production in a blood perfused canine heart subjected to 24 hours or 30 hours
      ischemia. The hearts were flushed with 100 mM histidine containing buffered
      solution (HBS) in one group and a second group and University Wisconsin solution
      (UWS) in a third group. The hearts were preserved at 4 degrees C for 24 hours in
      one and third group, and for 30 hours in a second group, then reperfused with
      autologous blood in an isolated heart perfusion apparatus. Standardized stroke
      volume, ejection fraction, developed pressure and end-systolic elastance were
      measured at 2 hours after reperfusion and compared with control non-preserved
      hearts. Better recovery of cardiac performance was attained in the hearts
      preserved with histidine containing cardioplegia for 24 hours or 30 hours than
      that in UW group. Although cardiac performances in the hearts preserved with
      histidine cardioplegia for 30 hours was worse than that in 24 hours preserved
      heart for 24 hour, those were comparable if low dose or high dose cathecolamine
      was given. We concluded that the histidine containing cardioplegia provides
      effective preservation of the canine heart with superior recovery of pump
      performance after 24 hours or 30 hours of preservation by buffering proton and
      lactate to promote anaerobic glycolysis.

PMID- 8551069
TI  - [Management of patients with closing aortic dissection].
AB  - Acute aortic dissection is a catastrophic event requiring immediate diagnosis and
      definitive treatment, while the clinical characteristics of closing aortic
      dissection are not well known. From Jan. 1991 through Dec. 1994 a total of 24
      patients with closing aortic dissection (CAD) was managed at our institution.
      There were 19 men and 5 women, ranging in age from 49 to 74 years with a mean of
      65 years. All patients presented with a sudden onset of severe chest and back
      pain. Twenty patients had a history of hypertension with a wide mediastinal
      silhouette on chest X-ray. The diagnosis of CAD was established by contrast
      computed tomographic (CT) scans in all patients with no evidence of patent false
      lumen. The descending thoracic aorta was involved in 17 patients and the
      ascending in 5. Conservative medical management was initially attempted for all.
      Seven patients (Stanford type A/B: 2/5) ultimately required surgical
      intervention, and 2 patients died. The follow-up was 100% complete with a mean
      term of 14.6 months. The overall survival rate was 74% at 3 years after the
      initial presentation. Based on our clinical experience, all patients with CAD
      need careful antihypertensive therapy and frequent follow-up studies to assess
      the aorta.

PMID- 8551070
TI  - [Cerebral infarction after the cardiovascular operation].
AB  - From January, 1990 through July 1994, 615 adult patients were undergone
      cardiovascular operation under the cardiopulmonary bypass. Sixteen patients were
      suffered perioperative cerebral infarction. The etiology of the cerebral
      infarction was evaluated on the pre and postoperative brain CT findings by the
      neurologists. In the 283 coronary artery bypass operations, 4 patients suffered
      watershed infarction (WS) and 4 cerebral embolism. In the 252 valve operations,
      one WS and one embolism. In the 80 thoracic aortic operations, 5 WS and one
      embolism, respectively. The risk factors of WS were the elderly, emergency, the
      longer operative period, and the longer cardiopulmonary bypass period. The risk
      factor of the embolism were male, preoperative cerebral infarction, the calcified
      finding of the ascending aorta by the chest CT. It is important to take
      preventive strategies against the watershed infarction.

PMID- 8551071
TI  - [Influence of warm ischemia and reperfusion on no-derived cyclic GMP release in
      the perfused rabbit lung].
AB  - To elucidate the vascular endothelial function at pulmonary ischemia and
      reperfusion, cyclic GMP (cGMP) release in lung perfusate at reperfusion after
      ischemia was examined as a marker of nitric oxide (NO) release from the
      endothelium in an in situ perfused rabbit lung. The lung was perfused from the
      pulmonary artery with Krebs-Henselite buffer and cGMP in the lung effluent from
      the left ventricle was assayed in a time-dependent manner. The inhibition of cGMP
      release by NG-nitro-L-arginine methyl ester and the reversal of the effect by L
      arginine indicated that cGMP released into the perfusate was elicited by NO from
      the endothelium. There was a significant decrease in cGMP release during
      reperfusion after warm ischemia (30 min and 60 min) compared with the immediately
      perfusion without intervening ischemia. These data suggest that NO release is
      impaired by the endothelial dysfunction at reperfusion after warm ischemia in the
      perfused rabbit lung and the biochemical studies of the perfusate is useful in
      assessing the vascular endothelial function.

PMID- 8551072
TI  - [A comparison of changes of cerebrovascular oxygen saturation in retrograde and
      selective cerebral perfusion during aortic arch surgery].
AB  - To evaluate the effect of retrograde cerebral perfusion (RCP) and selective
      cerebral perfusion (SCP) on brain protection, changes of cerebrovascular oxygen
      saturation (rSO2) were studied in 14 patients with aortic arch reconstruction
      during the procedure. The rSO2 was monitored with spectroscopy instrument (Invos
      3100, Somanetics). The mean value of rSO2 measured just before cardiopulmonary
      bypass was 65.9 +/- 6.2% in 7 patients with RCP, and was 64.9 +/- 4.7% in 7
      patients with SCP. The value of rSO2 during core cooling of cardiopulmonary
      bypass was increased step by step. Although RCP time with a mean of 38.9 +/- 9.7
      min was statistically shorter than SCP time (80.7 +/- 45.1 min), the mean value
      of rSO2 during cerebral protection in RCP group was decreased from 80.3 +/- 8.1%
      to 63.4 +/- 10.2%, lowest 46% with a ratio of 21.1%. In contrast, the mean value
      of rSO2 in SCP group was well maintained from 79.9 +/- 6.5 to 75.6 +/- 6.8%,
      lowest 63% with a ratio of 5.4%. Although no neurological deficits were
      recognized after operation in both groups, rSO2 in SCP group was sustained above
      the control value (65% just before cardiopulmonary bypass) but rSO2 in RCP group
      was decreased below the control value after 35 min. So we conclude that with
      regard to brain protection assessed from rSO2 measured by Invos 3100 cerebral
      oximeter, there is no time limitation of SCP during the procedure but RCP had a
      limit of the duration.

PMID- 8551073
TI  - [Immunohistochemical study of transforming growth factor-beta and central
      fibrosis in T1 adenocarcinoma of the lung].
AB  - Transforming growth factor-beta (TGF-beta) is known as the growth factor that
      stimulates the multiplication and accumulation of extracellular matrix. Recently,
      TGF-beta also has been found to have the ability to control the growth and
      metastatic potential of cancer cells. It is known that central fibrosis
      frequently occurs in pulmonary adenocarcinoma and the prognosis becomes poorer as
      fibrosis become more hyalinized. To estimate the role of TGF-beta in the
      formation of central fibrosis in pulmonary adenocarcinoma and its influence on
      the prognosis of patients with pulmonary adenocarcinoma, we performed an
      immunohistochemical study of TGF-beta in 51 cases of T1 pulmonary adenocarcinoma.
      Positive stain for TGF-beta was shown in 31 cases, and negative stain was shown
      in 20 cases. In patients with Stage I, T1 pulmonary adenocarcinoma, the post
      operative survival curve was compared between positive and negative cases of TGF
      beta, and the result showed a tendency toward poorer prognosis in positive cases
      of TGF-beta. Twenty-four of 51 cases of T1 pulmonary adenocarcinoma had central
      fibrosis. Twenty of 24 cases with central fibrosis showed positive stain for TGF
      beta. It was proven that the appearance of central fibrosis was significantly
      related to positive stain for TGF-beta in T1 pulmonary adenocarcinoma. According
      to these results, it is suggested that TGF-beta plays some role in the formation
      of central fibrosis in pulmonary adenocarcinoma and TGF-beta is possibly a
      prognostic factor for patients with pulmonary adenocarcinoma.

PMID- 8551074
TI  - [Correlation between pulmonary vascular changes and hemodynamic parameters during
      exercise before and after mitral valve surgery].
AB  - Sixteen cases with mitral valvular disease were studied with regard to the
      correlation between pathological changes in the pulmonary vasculature and
      pulmonary hemodynamics during exercise before and after surgery. In muscular
      pulmonary arteries obtained by open lung biopsy, medial wall thickness (MWT) was
      13.8 +/- 3.2% and intimal thickness (IT) was 37.3 +/- 13.5%. MWT was correlated
      with IT (r = 0.60, p < 0.05). Wall thickness in pulmonary veins was 8.21 +/-
      1.8%. Preoperative mean pulmonary arterial pressure (MPAP) during exercise was
      45.9 +/- 9.4 mmHg, and decreased significantly to 38.1 +/- 11.3 mmHg
      postoperatively. However, in 4 patients, MPAP during exercise increased after
      surgery. Pulmonary vascular resistance (PVR) during exercise was unchanged before
      and after surgery (2.74 +/- 1.90 U.M2-->2.69 +/- 1.3 U.M2). MWT was significantly
      correlated with preoperative MPAP at rest only. In patients showing an increase
      of MPAP during exercise postoperatively, mean MWT was 16.2% and mean IT was
      47.4%. In conclusion our data suggest that postoperative pulmonary hemodynamics
      does not improve in patients whose MWT exceeds 15% and IT exceeds 40% and that
      irreversibility may be due to pulmonary vascular lesions.

PMID- 8551075
TI  - [Selection of the surgical methods and surgical outcome of the distal arch
      aneurysm].
AB  - Between January, 1985, and December, 1993, 20 patients (18 males, 2 females;
      median age 65 years) underwent repair of aneurysms of the distal arch. fourteen
      patients had sacciform aneurysms and 6 patients had fusiform aneurysms. The
      approaching methods to the aneurysms were left thoracotomy in 3 patients and
      median sternotomy in 17 patients, including the so-called "door open method" in 2
      patients. The supportive methods during surgery were left heart bypass using a
      centrifugal pump in 3 patients cardiopulmonary bypass with selective cerebral
      perfusion in 11 patients, and cardiopulmonary bypass with retrograde cerebral
      perfusion in 6 patients. The operative methods were patch closure in 4 patients,
      graft replacement using the inclusion technique in 13 patients, and total arch
      replacement using the exclusion technique in 3 patients. One patient who
      underwent left heart bypass died intraoperatively from intractable bleeding, one
      who had undergone selective cerebral perfusion died postoperatively of rupture of
      the distal anastomosis and two patients, who were supported with retrograde
      cerebral perfusion, died postoperatively because of perioperative myocardial
      infarction or rupture of the dissection arising from the aneurysm. There were
      three cases with cerebral complications postoperatively. These three patients
      were supported with selective cerebral perfusion. Graft exclusion technique using
      a prosthetic graft with three branches under the retrograde cerebral perfusion
      shortened cardiopulmonary bypass time and heart and brain ischemic time, so that
      this technique might reduce cerebral complications and should be a promising
      surgical treatment for the distal arch aneurysm.

PMID- 8551076
TI  - [A case of so-called carcinosarcoma of the esophagus].
AB  - So-called carcinosarcoma of the esophagus is rare malignant tumors composed of
      carcinoma and sarcomataous components. We described a case of so-called
      carcinosarcoma and reviewed some literature. A 67-year-old man visited our
      hospital because of difficulty in swallowing, general fatigue, and sore throat.
      Barium swallow esophagogram showed a large polypoid lesion in the middle, lower
      thoracic esophagus. Endoscopy also demonstrated a pedunculated polypoid tumor.
      Histological examination of the biopsy specimen revealed malignant findings.
      Thoracic esophagectomy with cervical, thoracic, abdominal dissection was
      performed. A polypoid tumor, 10.5 x 5.2 x 3.5 cm in size, was removed. In the
      polypoid lesion, spindle-shaped cells made interlacing bundles similar to sarcoma
      and surrounded nests of squamous cell carcinoma. Near the pedicle, squamous cell
      carcinoma invaded muscularis mocosae. And lymph node metastasis was detected.
      Epitherial membrane antigen (EMA) was detected in some parts of the polypoid
      lesion. So according to Guide Lines for Clinical and Pathological Studies on
      Carcinoma of the Esophagus, this case was diagnosed as so called carcinosarcoma.

PMID- 8551077
TI  - [A case of esophageal cancer required jejunal reconstruction because of a gastric
      ulcer scar].
AB  - Recently, with increase of number of esophagectomy for esophageal cancer, the
      cases having the lesion in the organs for esophageal substitute have been
      increasing. The case of esophageal cancer, required reconstruction using the
      pedicled jejunum, because of impaired submucosal blood perfusion of the stomach
      caused by a ulcer scar, was reported. The patient was a 72-year-old female, with
      the ulcerative and infiltrative cancer lesion in the anterior wall of the mid
      thoracic esophagus. Barium swallow revealed shortening of the lesser curvature
      and indentation of the greater curvature of the stomach. Endoscopy showed the
      lesion occupying anterior two thirds of the esophageal wall circumferentialy from
      30 to 34 cm from the incisor tooth. The lineal scar of ulcer on the lesser
      curvature of the body of the stomach was also found. Following esophagectomy
      through right thoracotomy, the stomach was mobilized for reconstruction by
      dividing left gastric artery and short gastric artery, but the stomach oral to
      the ulcer scar became ischemic and bleeding was not found at the tip of the
      stomach. Therefore, reconstruction was performed using the pedicled jejunum
      through antesternal route. The gastric cardia is rich in the vascular network in
      the submucosal layer. The ulcer or ulcer scar of this region can cause ischemia
      in the tip of the gastric tube for esophageal substitute. Care should be taken to
      detect the ulcer lesion at the stomach preoperatively. In the case with the ulcer
      lesion blood supply to the tip of the gastric tube should be critically
      evaluated.

PMID- 8551078
TI  - [Surgery of thoracoabdominal aortic aneurysm associated with coronary artery
      disease].
AB  - A 67-year-old man underwent combined surgery for thoracoabdominal aortic aneurysm
      and coronary artery disease. Preoperative computed tomographic scan and
      aortography showed a large aneurysm in diameter of 7 cm locating from lower half
      of the descending thoracic aorta to just above the celiac artery. Coronary
      arteriography revealed severe stenosis (99%) of the proximal left anterior
      descending artery (LAD). The patient was operated on in October 1994, via a
      thoracoabdominal approach by entering the thorax in the 8th intercostal space and
      the retroperitoneal space through a paramedian incision after division of the
      costal arch. An additional standard thoracotomy was performed in the 5th
      intercostal space, through which a left internal thoracic artery (LITA) was
      mobilized. After the proximal descending thoracic aorta as well as the right
      femoral artery was cannulated for arterial perfusion, and the main pulmonary
      artery as well as the right femoral vein for venous return, total cardiopulmonary
      bypass was established and a LITA graft was anastomosed to the LAD under
      cardioplegic arrest. Thereafter the aneurysm was replaced with an 18 mm dacron
      prosthesis while the LITA graft and coronary arteries were reperfused and cardiac
      beating was resumed. His postoperative course was uncomplicated. Postoperative
      angiography demonstrated satisfactory repair of the aorta and a fully patent LITA
      graft.

PMID- 8551079
TI  - [The internal thoracic artery of poor quality: was cardiac massage a cause of ITA
      stenosis?].
AB  - The case of stenotic left internal thoracic artery (LITA), with a very rare and
      interesting histological findings is reported. The patient, a 65-year-old man,
      fell into shock, due to acute myocardial infarction and received cardiopulmonary
      resuscitation at home immediately. Three months later, patient underwent coronary
      artery bypass grafting. The LITA was dissected from the chest wall with a tissue
      pedicle by usual manner. However, it was abandoned to use for grafting, because
      of extremely poor blood flow even after balloon dilatation was noticed.
      Histological study revealed a significant granulation of LITA media, led to
      severe stenosis of LITA lumen on it's portion. On other side, either proximal and
      distal portion of LITA remained intact. It seems that this unusual histological
      change of LITA media developed after LITA over stretching due to cardiac massage
      during cardiopulmonary resuscitation. If patient, scheduled for coronary bypass
      surgery, has in a personal history the presence of cardiac massage, traffic
      accident, some contact sport or any other chest trauma, it is recommended to
      perform LITA angiography preoperatively, if an intention to use the LITA for
      coronary artery bypass grafting exists.

PMID- 8551080
TI  - [Dissection of the pseudointima followed by lethal obstruction of the prosthetic
      graft--a case report].
AB  - One-year-old boy who previously had modified Van Praagh procedure for
      interruption of the aortic arch (Celoria-Patton type A) and double inlet left
      ventricle with ventriculoarterial discordance was admitted for progressive
      cyanosis. He underwent reconstruction of the left pulmonary artery and additional
      left common carotid-left pulmonary artery shunt. During this procedure, severe
      hypotension of the lower extremities and heart failure occurred for unknown
      cause. He died on the 7 postoperative day for lung bleeding with disseminated
      intravascular coagulopathy. Autopsy revealed dissection of the pseudointima and
      obstruction of the prosthetic graft (interposed between the main pulmonary artery
      and the descending aorta). This complication seems very rare but a great care
      should be taken when a prosthetic graft is manipulated later.

PMID- 8551081
TI  - [Preoperative plasmapheresis for lung cancer with multiple myeloma].
AB  - A 66-old-male admitted to our hospital was diagnosed multiple myeloma (IgA kappa
      type, Durie & Salmon stage IIIA) and squamous cell lung cancer (c-T2N0M0 stage
      I). The function of platelets was within a normal range (11.7 x 10(4)/mm3 and the
      bleeding time of two minutes), but the function of coagulation was reduced
      (prothrombin time, 13.1 seconds; activating prothrombin time, 45.1 seconds; and
      antithrombin III, 65%). The hyperviscosity syndrome was anticipated because of
      high IgA M protein (6,551 mg/dl). Plasmapheresis with 800 ml of fresh frozen
      plasma was performed before the left lower pulmonary lobectomy and R1 lymph node
      dissection. Then the function of coagulation was improved (prothrombin time, 12.6
      seconds; activating prothrombin time, 31.3 seconds; and antithrombin III, 75%).
      IgA M protein was also decreased to 4,696 mg/dl. Postoperative bleeding
      necessitated a second thoracotomy. The cause of postoperative bleeding was the
      ablasion of the pleural adhesion due to tuberculous pleuritis as well as bleeding
      tendency of multiple myeloma. The plasmapheresis performed in this case did not
      fully improve the bleeding tendency. Cases of cancer complicated with multiple
      myeloma have been increasing and if an operation is needed, plasmapheresis should
      be considered. The indication and the extent of hematologic restoration to be
      achieved should be further investigated.

PMID- 8551082
TI  - [Successful surgical treatment in a case of type IIIb acute aortic dissection
      complicated with acute myocardial infarction].
AB  - The patient was a 48-year-old man who was brought to our hospital complaining of
      chest pain, paresthesia of the lower extremities, and pain in the lumbar region.
      At first, acute myocardial infarction was diagnosed, but transthoracic
      echocardiogram revealed an intimal flap in the ascending aorta. The presence of
      an intimal tear below the left subclavian artery was confirmed by intraoperative
      transesophageal echocardiogram, and a diagnosis of myocardial infarction
      accompanying type IIIb aortic dissection with retrograde extension to the
      ascending aorta was made. Coronary artery bypass grafting to segment #2 using a
      section of saphenous vein and total aortic arch replacement with "elephant trunk"
      technique, which concurrently served as a means of amputated stump plasty, was
      performed. The cerebral circulation was preserved by retrograde cerebral
      circulation. The post operative progress was good, and thrombo-occlusion of the
      false lumens of the proximal descending aorta was verified. Type IIIb aortic
      dissection complicated with myocardial infarction is rare, but examination with
      both transthoracic and transesophageal echocardiograms were useful for the
      morphological diagnosis and for determining the surgical technique for the
      dissection.

PMID- 8551083
TI  - [A case report on a reconstructive operation of a traumatic tricuspid
      regurgitation with a congenital defect of the left pericardium].
AB  - We reported a successful tricuspid valve replacement in a 58-years old man, who
      had easy fatiguability after 14 years of a blunt chest trauma. The preoperative
      examination revealed a marked cardiomegaly with deformation of both ventricles
      and grade 4 tricuspid regurgitation caused by the prolapse of the anterior
      leaflet. The operative inspection revealed a left pericardial defect with a
      diameter of 10 cm and a torn anterior papillary muscle. Since a usual plastic
      procedure did not improve the regurgitation, a Carpentier-Edward bioprosthetic
      valve was implanted in the supra annular position. Atrioventricular conduction
      was preserved. The tricuspid valve was not resected to preserve the ventricular
      function. The patient recovered his own activity.

PMID- 8551084
TI  - [A successful palliative arterial switch operation with arch repair for tricuspid
      atresia with ventriculoarterial discordance, subaortic stenosis, coarctation, and
      aortic arch hypoplasia].
AB  - A successful palliative arterial switch operation with arch repair in a 30-day
      old infant with tricuspid atresia, ventriculoarterial discordance, subaortic
      stenosis, coarctation of the aorta, and aortic arch hypoplasia is reported. A
      concomitant Blalock-Taussig shunt was required because of insufficient pulmonary
      blood flow through the restrictive bulboventricular foramen. Postoperative
      arterial oxygen saturation was maintained around 90% and the pressure gradient
      between the left ventricle and the pulmonary artery was 45 mmHg according to a
      Doppler echocardiogram. The infant becomes free of subaortic stenosis and is
      awaiting the subsequent Fontan operation. This alternative palliative operation
      for neonates and early infants with double inlet ventricle, subaortic stenosis,
      and arch hypoplasia offers some advantages on the Fontan operation for avoiding
      pulmonary arterial distortion and subaortic stenosis followed by ventricular
      hypertrophy.

PMID- 8551085
TI  - [A successful surgical replacement for mitral regurgitation after cardiac arrest
      due to widely ruptured chordae tendineae].
AB  - A 47-year-old woman, who has mitral regurgitation previously diagnosed in another
      hospital, was transferred to our intensive care unit for acute congestive heart
      failure. Just after admission, her respiratory state became worse and she
      suddenly fell into cardiac arrest. Five minutes later she recovered through
      cardiopulmonary resuscitation. The pulmonary artery pressure, however, which
      reached 85/43 mmHg with a Swan-Ganz catheter, had been exceeding systemic
      pressure. On echocardiography ruptured chordae tendineae of the mitral anterior
      leaflet was most suspected. Five days after the intensive treatment with a use of
      IABP, we operated upon her. On the operative findings most rough zone chordae of
      both leaflets including two strut chordae were ruptured with severe prolapsing.
      Thus we chose prosthetic valve replacement rather than mitral valve repair. We
      replaced the mitral valve with a Carbomedix 25 mm. Postoperatively the mean
      pulmonary artery pressure remained still high as 40 mmHg. With a continuous
      intravenous administration of prostaglandin E1, the pulmonary artery pressure
      became lower gradually. The patient was able to wean from respirator on the 18th
      postoperative day. The patient was discharged on the 49th postoperative day. The
      mitral valve removed at operation showed myxomatous degeneration and idiopathic
      ruptured chordae tendineae on the pathological examination. In summary a 47-year
      old woman underwent mitral valve replacement 5 days after cardiac arrest from
      acute severe mitral regurgitation due to widely ruptured chordae tendineae of
      both leaflets. She survived the operation and got well. The mitral valve showed
      myxomatous degeneration on pathological examination.

PMID- 8551086
TI  - [Development and progression of pyogenic spondylitis in a canine experimental
      model].
AB  - An experimental model was prepared to investigate the process of inflammation in
      pyogenic spondylitis. Forty-seven mongrel dogs were used, involving 24 mature and
      23 immature dogs. Under intravenous pentobarbital anaesthesia, the lumbar
      vertebral bodies were approached posterolaterally and inoculated using a small
      piece of gauze soaked in a staphylococcus aureus suspension. Roentgenographic and
      histological examinations were regularly performed for 24 weeks after the
      inoculation. Histologically, acute inflammation started within 1 or 2 weeks, and
      subsided by 5 or 6 weeks in both the mature and immature dogs. In 55% of the
      dogs, the inflammation was confined within the vertebral body, in 10% it invaded
      into the intervertebral disc, and in 35% inflammation invaded into the anterior
      longitudinal ligament. In the immature dogs, thickening of the trabeculae and the
      anterior cortex was observed around the inflammatory focus more often than in the
      mature dogs. The epiphyseal line acted as a barrier against invasion by the
      inflammation in the immature dogs. However, direct invasion of the inflammatory
      process into the disc could have occurred through the vascular buds which were
      the terminal branches of the metaphyseal artery close to the disc in both the
      mature and immature dogs. In contrast to the results reported by Ohno who
      inoculated the lumbar discs of mongrel dogs with staphylococcus aureus, in the
      present study, the disc space remained intact and was replaced by fibrous tissue.
      Consequently, it was concluded that pyogenic spondylitis should be defined as a
      different clinical entity from discitis.

PMID- 8551087
TI  - [Nerve sutures and nerve grafts for repairing a gap in peripheral nerve injury:
      an experimental study].
AB  - An experimental study was performed using the canine sciatic nerve in order to
      compare the efficacies of a vascularized trunk graft (VTG), a free trunk graft
      (FTG), a vascularized cable graft (VCG), a free cable graft (FCG) and a two stage
      procedure (TSP) for the repair of a peripheral nerve defect. Both a 4 cm, and a 5
      cm nerve defect was repaired using each method, and also a 6 cm defect, using VCG
      and FCG. After 24 weeks, the intraneural blood flow (IBF) was measured in the 4
      cm defect group, and the recovery of nerve regeneration and muscle reinnervation
      were evaluated by motor nerve conduction velocity, wet muscle weight, and
      histological examinations of the nerve and the muscles. VTG and VCG both
      demonstrated superior IBF. The IBF after TSP was less than after VTG and VCG but
      greater than after FTG and FCG. In the 4 cm defect group, VTG showed the most
      favorable recovery in both the axonal regeneration and muscle reinnervation and
      was followed by VCG. Although the recovery after FTG, FCG and TSP appeared to be
      worse than after VTG and VCG, there was no significant difference. In the 5 cm
      defect group, VTG showed the most favorable recovery followed by VCG and FCG. For
      axonal regeneration, FTG was significantly worse than VTG, VCG and FCG. TSP was
      worst within the 5 cm defect group for muscular reinnervation, although it showed
      somewhat better axonal regeneration than FTG. In the 6 cm defect group, no
      significant difference was found between VCG and FCG for the axonal regeneration.
      Clinically, TSP is used for repairing a short nerve defect just beyond the
      critical distance that cannot be overcome by a primary end-to-end suture. Nerve
      grafting, other than FTG, appeared to be the most reliable method of bridging a
      long nerve defect, and FCG might be the most practical method.

PMID- 8551088
TI  - [Effect of intermittent administration of human PTH on experimental osteopenia in
      adult rat: a histomorphometric study of both trabecular and cortical bone of the
      vertebrae].
AB  - Both the cancellous and the cortical envelopes of the vertebral bone of
      osteopenic rats were histomorphometrically evaluated to elucidate the effect of
      an intermittent administration of h-PTH (1-34) on bone remodeling. Seven-eight
      month-old female Wistar rats were used, and osteopenia was produced by
      ovariectomy, by prednisolone administration, or by streptozotocin-induced
      diabetes mellitus. The rats were divided into 10 groups; as base line control
      rats, vehicle administered rats, and h-PTH administered rats for each of the
      three kinds of osteopenia, and sham operated rats. Vehicle or h-PTH was
      administered subcutaneously six times a week from the 9th to the 12th week of the
      experiment. The dosage of h-PTH was 6.0 micrograms/kg. Ovariectomy developed a
      high turn-over osteopenia, and prednisolone administration and diabetes mellitus
      caused a low turn-over osteopenia. All 3 kinds of osteopenia showed similar
      changes in histomorphometric parameters after h-PTH treatment. In the cancellous
      envelope, the bone volume increased significantly in all groups. The trabecular
      thickness, osteoid surface, mineralizing surface, mineral apposition rate, and
      the bone formation rate increased in all groups after the treatment with h-PTH.
      The eroded surface significantly decreased except in the diabetes mellitus rats.
      In the endocortical envelope, the osteoid surface, mineralizing surface and the
      mineral apposition rate increased in all groups. The eroded surface significantly
      decreased in all groups after the treatment with h-PTH. The cortical thickness
      significantly increased except in the ovariectomized rats. The results of the
      present study suggested that an intermittent administration of h-PTH stimulated
      bone formation without increasing bone resorption in all three kinds of
      osteopenia induced by ovariectomy, corticosteroid, or diabetes mellitus.

PMID- 8551089
TI  - [Bone formation and mechanical properties of the cancellous bone defect site
      filled with hydroxyapatite granules].
AB  - We investigated the co-relationships of the granule size of hydroxyapatite with
      the amount of new bone formation and with mechanical properties at the bone
      defect site filled with hydroxyapatite granules. In this experimental study,
      cylindrical bone defects 6.4 mm in diameter and about 1 cm in depth were prepared
      in the bilateral femoral condyles and in the tibial condyles of large albino
      rabbits (body weight 5.1-7.3 kg), filled with three types of hydroxyapatite
      granules 0.3-0.6 mm, 0.6-1.0 mm, and 1.0-2.0 mm in diameter, and examined after
      2, 4, and 8 weeks after sacrificing the animals. Two animals (4 limbs) each were
      examined for the same granule size and the same period after filling.
      Undecalcified sections of the tibia at the defect site were examined
      histologically, and the volume and surface of hydroxyapatite, the volume of new
      bone, the surface of the new bone in contact with hydroxyapatite, and the percent
      of this surface relative to the entire surface of hydroxyapatite were determined.
      Columnar specimens 6.0 mm in diameter and 5.0 mm in length were prepared from the
      defect sites of the femur, compressed at a deformation rate of 2.4 mm/min, and
      the failure stress, stiffness, and energy absorption were calculated from the
      load-deformation curve. The normal cancellous bone from 2 unoperated animals (4
      limbs) and bone defect sites not filled with hydroxyapatite granules of 2 animals
      (4 limbs) were examined as controls. A greater amount of new bone was formed as
      the granule size was smaller. After 8 weeks, the failure stress and energy
      absorption were higher as the granule size was smaller, and the mechanical
      properties of the bone defect sites filled with 0.3-0.6 mm granules were similar
      to those of normal cancellous bone.

PMID- 8551090
TI  - [Efferent spinal evoked potentials by transcranial magnetic stimulation in dog].
AB  - We have investigated the utility of transcranial magnetic stimulation for spinal
      cord monitoring, experimentally in dog. Experiment 1. Spinal cord potentials
      evoked by transcranial magnetic stimulation (TCMS) were recorded in the epidural
      space, using a bipolar mapping spinal electrode, and compared with potentials by
      transcranial electrical stimulation (TCES). Experiment 2. The effect of lateral
      compression on the spinal cord was observed, recording from 3 bipolar electrodes
      attached to the bilateral and dorsal midline epidural space. Experiment 3. The
      potentials evoked by TCMS were compared with the afferent potentials evoked by
      spinal electrical stimulation after lateral compression of the spinal cord.
      Efferent spinal cord potentials evoked by TCMS consisted of a 1 st component of
      high amplitude and short latency and a later polyphasic component with prolonged
      latency. The 1 st component was stable, and not affected by intravenous
      anesthesia. The potentials evoked by TCMS were similar to the potentials evoked
      by mild TCES, and the mean latency of the 1 st component by TCMS was very similar
      to that by mild TCES. After releasing the lateral compression, the amplitude
      recorded from the contralateral side of the spinal cord showed better recovery
      than that from the compression side. In experiment 3, for both potentials after
      good recovery, the latency was almost completely normalized, but the amplitude
      gradually decreased after two days. When there was relatively good recovery in
      the potentials by magnetic stimulation, the hind limbs resumed normal function.
      However when there was poor recovery in the potentials, the hind limbs showed a
      poor functional recovery. From these findings, we concluded that the potentials
      evoked by TCMS seem to reflect the function of the posterolateral portion of the
      spinal cord. These potentials were therefore a good indicator for monitoring the
      motor function of the spinal cord.

PMID- 8551091
TI  - [Effect of human PTH on steroid-induced osteopenia: a histomorphometric study of
      decalcified and undecalcified trabecular bone sections in rat].
AB  - Serum and urine chemical analyses were combined with a bone histomorphometrical
      study of rat metaphyses to evaluate the osteogenetic effect of intermittent
      administration of human parathyroid hormone (h-PTH) on steroid-induced
      osteopenia. Seven-month-old female Wistar rats were divided into the following 4
      groups: (1) a control group: age-matched and untreated; (2) a baseline control
      group (BL group): given 2.5 mg/kg prednisolone subcutaneously 6 times/week for 8
      weeks, at the end of which the animals were sacrificed; (3) a PTH group: in the
      9th week of continuous steroid administration, 6.0 micrograms/kg h-PTH was added
      to the regimen; and the animals were sacrificed in the 12th week; (4) a vehicle
      group, as a control for the h-PTH group: only the vehicle was administered
      instead of PTH. At the necropsy at the end of the experiment, both tibias were
      collected. The undecalcified sections were stained by Villanueva bone stain and
      labelled with tetracycline, and the decalcified sections were stained by TRAP,
      and examined histomorphometrically. Serum Ca and P were not changed by any
      treatment. Serum 1,25 (OH)2D3 values were significantly increased in rats treated
      with h-PTH. There was no significant change in urinary Ca, P, or hydroxyproline
      excretion in any group. Histomorphometrically, the parameters related to bone
      formation--osteoid surface, mineralized surface and bone formation rate--were all
      reduced in the BL group and in the vehicle group. The bone volume was
      significantly lower in these group than in controls. The PTH group, on the other
      hand, showed increases in the osteoid surface, mineral apposition rate, and bone
      formation rate and the bone volume was significantly higher than in controls. The
      PTH group showed no increases in the osteoclast number or in the osteoclast
      surface. These results suggested that intermittent administration of h-PTH
      activated bone formation only, and increased bone volume.

PMID- 8551092
TI  - [Somatosensory evoked potentials for the diagnosis of carpal tunnel syndrome].
AB  - The middle latency somatosensory evoked potential (SEP), in particular the N60 of
      median nerve SEP, can be recorded in patients with severe peripheral neuropathy
      even in the absence of a recordable compound muscle action potential (CMAP).
      However, clinical utilization of N60 is hampered by its inter-trial variabilities
      that depend on the level of consciousness, habituation, stimulus rate and/or
      other unknown factors. We have now obtained a stable N60 SEP when the subject
      stays awake and alert using a slow stimulus rate. We have applied this method to
      17 hands of 15 patients with severe carpal tunnel syndrome (CaTS) whose CMAP were
      not recordable. The stimuli were applied to two sites: one was 2 cm proximal to
      the distal crease at the wrist and the other was on the middle finger. SEP were
      recorded from a central electrode contralateral to the side of stimulation and
      referenced to the bilateral ear. In normal subjects, the estimated conduction
      velocities between the distal crease and the middle finger measured by the N60
      latency difference ranged from 45.1 to 89.2 m/sec with a mean velocity of 67.4 +/
      13.0 m/sec. In 12 CaTS hands, the stimulation of the fingers resulted in a
      significantly delayed N60 (8 hands) or no response (4 hands). The estimated
      conduction velocity in CaTS ranged from 9.3 to 21.2 m/sec with mean velocity of
      15.6 +/- 4.2 m/sec. In order to localize the point of maximal conduction delay in
      the CaTS, a further 17 hands were examined by stimulation of the median nerve at
      multiple sites across the carpal tunnel.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8551093
TI  - [A comparative study between magnetic resonance imaging and histological findings
      of bone and soft tissue tumors].
AB  - Diagnostic methodology for bone and soft tissue tumors has made great strides
      recently through the development of magnetic resonance imaging (MRI). Here we
      report a comparative assessment of the histological findings of bone and soft
      tissue tumors with MRI from 212 cases. The accuracy of a qualitative diagnosis
      was observed in a solitary bone cyst, enchondroma, giant cell tumor,
      chondrosarcoma, lipoma, hemangioma, neurinoma, and in a synovial cyst. However,
      the qualitative diagnosis of a malignant tumor was difficult because of the
      variety of the intratumoral histological changes. An enhanced-image using Gd-DTPA
      was useful for differentiation of the viable region in the internal area of a
      tumor, discrimination of the rective zone of an edema or assessing vascularity,
      and for discrimination between a cyst and a solid tumor. Based on comparison with
      findings from the excised specimen, it was found that histological changes such
      as calcification, fibrosis, hemorrhaging and necrosis, and the presence or
      absence of a tumor capsule had been reflected accurately on MR images. However,
      infiltration of the tumor into the bone cortex and into the articular cartilage
      were found frequently to be false-positive on MRI. Although problems remained to
      be solved regarding the evaluation of the presence or absence of tumor
      infiltration into adjacent tissue, the depiction of periosteal reaction, and
      regarding differentiation from inflammatory disease, MRI was a very useful
      information source for operative planning because it could evaluate the
      relationship between the tumor and adjacent blood vessels or nerves, the effect
      of preoperative therapy, and effectively discriminate between benign and
      malignant tumors.

PMID- 8551094
TI  - [Trunk deformity in scoliosis studied by surface measurement].
AB  - Ihe three-dimensional back surface shape of 504 patients with untreated
      idiopathic scoliosis was studied using moire topography. A new system for the
      quantitative analysis of moire pictures was developed with the aid of a still
      video photo system and microcomputer system. With these systems, the outcome of
      the analysis can be obtained immediately at the clinical scene. Using a
      positioning device that restrained the movement of the patient's pelvis at the
      time of taking the moire picture, the reproducibility error was very small. The
      relationship of the parameters from the surface measurements with the
      radiographic appearance was then examined. The hump sum (HS), that is the sum
      total of the hump indices on three levels of the back was used as an index that
      represented the severity of the trunk deformity. It was possible to estimate
      objectively from HS, the correction in trunk deformity obtained after treatment.
      There was a relatively weak but statistically significant number of cases in
      which the degree of hump and that of the lateral curvature did not agree. Those
      within the range of one standard deviation from the regression line were defined
      as the standard rotation group, and those out of this range as the nonstandard
      rotation group. In the standard rotation group, the progression in curvature
      could be detected by moire analysis so that exposure to radiation could be
      reduced. In the nonstandard rotation group, radiographic examination remained
      necessary, although the magnitude of the trunk deformity itself could be
      estimated more accurately by HS. The discrepancy between the HS and the Cobb
      angle suggested that scoliosis and rib deformity were independent from each
      other, and therefore they should be evaluated separately.

PMID- 8551095
TI  - [Mechanism of the radiolucence around the implant after hip prosthetic
      replacement].
AB  - After hip prosthetic replacement, a progressive enlargement in the radiolucent
      area has often been observed around the implant, leading to loosening of the
      prosthesis. The purpose of this study was to investigate the mechanism of the
      radiolucent area formation. Radiolucent areas can be classified into either
      linear type or the erosive type, and these two types were compared histologically
      and biochemically. Interface membranes were obtained from patients at the time of
      surgery for revision of either cemented THA or cementless bipolar endprosthetic
      replacement. Histological specimens were stained by H.E., tartrate-resistant acid
      phosphate, and by the immunohistochemical reagents anti-macrophage antibody (CD
      68), anti-T-lymphocyte (CD 3, CD 4, CD 8, CD 43), anti-interleukin-1 beta
      polyclonal antibody, anti-interleukin-6 polyclonal antibody, and anti-tumor
      necrosis factor-alpha polyclonal antibody. Biochemically, interleukin-1 beta, IL
      6, IL-8, TNF-alpha were assayed by ELISA in the supernatant of homogenized
      samples and in organ culture media. Prostaglandin E2 was assayed by
      radioimmunoassay. The interfaces of the erosive type contained more debris
      (cement, high density polyethylene and metal), macrophages and multinucleated
      giant cells than the linear type. The interfaces of the linear type showed mainly
      fibrosis and necrosis. The levels of IL-6 and IL-8 in the homogenates and culture
      media from the erosive type were significantly higher than those from the linear
      type. We concluded that the bone resorption around the implant after hip
      prosthetic replacement occurred by two different pathways. One pathway involved
      the stimulation of macrophages by various debris and micromovement to form
      foreign body granulomas, which produced cytokines, prostaglandin E2 and
      metalloproteinase to resorb bone. The erosive type would arise from this pathway.
      The other possible mechanism involved a biomechanically unstable implant which
      caused bone necrosis probably by mechanical stress. The linear type may arise
      from this pathway.

PMID- 8551096
TI  - [An anatomical study on the interosseous membrane of the forearm].
AB  - The anatomy of the interosseous membrane (IOM) was studied in 117 forearms from
      sixty cadavers (average age; 73 years old) for the purpose of optimizing the
      osteotomy portion in forearm lengthening, or in osteotomy for an old Monteggia
      fracture. The morphological anatomy of the interosseous membrane, and its
      relation anatomically to the surrounding structures were investigated. A total of
      68.4% of the IOM was classified as Type 1a or 1 b, in which one cord-like portion
      was observed. The accessory cord-like portion was found in 57.8% of the forearms.
      The cord-like portion was attached at a position of 39.6-54.8% from the distal
      end of the radial bone and at 21.9-42.1% from the distal end of the ulnar bone
      (average rate per forearm length). The accessory cord-like portion was attached
      at a position of 48.9-53.3% from the distal end of the radial bone and at 56.9
      61.8% from the distal end of the ulnar bone. From there results, the optimal
      portion for osteotomy in forearm lengthening and in old Monteggia fracture was
      determined to minimize the anatomical and functional damage to the forearm.

PMID- 8551097
TI  - [The medial epicondyle of the humerus, an anatomical study].
AB  - A large variation in the shape of the medial epicondyle is encountered. This
      study was performed to investigate any role of the shape of medial humeral
      epicondyle in the etiology of osteoarthritis in the elbow, which can lead to
      cubital tunnel syndrome. A total of 71 humerus from 36 cadaveric specimens (mean
      age 75, ranging from 52 to 93) were used to study the morphological
      characterization of the medial humeral epicondyle. The specimens were divided
      into four types according to the index of medial epicondylar breadth and medial
      epicondylar length. A correlation was found between the angle of inclination of
      the sulcus nervi ulnaris and osteophyte formation in the medial epicondyle. This
      finding suggested that Type 2 (wider type) and 3 (longer type) might each
      contribute to the onset of osteoarthritis, resulting in cubital tunnel syndrome.
      However, we found some cases of Type 1 (wider and longer type) with a large angle
      and only minor osteophyte formation, suggesting that a large inclination angle of
      the sulcus nervi ulnaris alone was not an independent factor in osteophyte
      formation. Moreover from our results of measuring the distance between the tip of
      the medial epicondyle and the medial edge of the anterior medial collateral
      ligament origin, we concluded that medial epicondylectomy (King's method) without
      damaging this ligament should be performed at a point approximately 20% of the
      overall width of the medial epicondyle from the tip of the medial epicondyle.

PMID- 8551098
TI  - [Intradiscal injection of hypertonic saline, phenol-glycerin and osmic acid for
      the treatment of lumbar disc herniation: an experimental study].
AB  - The present study was designed to investigate the possible clinical application
      of hypertonic saline (HS), phenol in glycerin (PHG) and osmic acid (OSA) for
      intradiscal therapy. MATERIALS & METHODS: HS in several concentrations, 10% PHG
      and 4% OSA were separately injected into the lumbar intervertebral discs of 60
      Japanese white rabbits. Additionally, these substances were placed directly on
      the dura of the spinal cord of 48 guinea pigs. The animals were sacrificed
      periodically and were submitted to histological examination using light
      microscopy. RESULTS: HS caused localized necrosis of the nucleus pulposus cells
      in a concentration-related fashion. Some discs decreased their height. With time,
      all the discs generally regained their normal histology. Following administration
      of 10% PHG, the area of necrosis of the nucleus pulposus cells was more extensive
      than that by HS, but the regenerative or reparative reaction was not so brisk.
      Examination of the discs treated with 4% OSA demonstrated severe changes in the
      nucleus pulposus and the inner annulus fibrosus with resultant disc-space
      narrowing. The reparative tissue seen after injection of OSA was fibrocartilage
      in nature. No histological change was seen in the surrounding tissue including
      the neural tissue following administration of any of the substances. DISCUSSION:
      Chymopapain is the substance most frequently used for clinical chemonucleolysis.
      The major clinical complication with chymopapain has been anaphylaxis. The
      present substances have been used in other clinical applications without reports
      of anaphylaxis. In this report, HS was shown to hold the potential for reducing
      intradiscal pressure without induction of scar tissue or significant loss of disc
      function. PHG and OSA caused considerable but circumscribed histological damage
      to the disc tissue, but had no such effect on the neural tissues. These data
      suggested that HS, PHG and OSA may have clinical applications as agents in
      intradiscal therapy.

PMID- 8551099
TI  - [A chronic spinal cord compression model in a rat with a 354A tumor].
AB  - A posterior spinal cord compression model was produced in a rat with a 354 A
      tumor. Here we report the compression process using MRI (at 2.11 tesla), the
      progression of paralysis in the posterior limbs, the pathological changes in the
      neural tissues, and the spinal evoked potentials (SpEPs). A relatively flat
      spinal cord compression model was established by the interposition of free fatty
      tissue between the tumor and dura mater. The anteroposterior diameter of the
      compressed cord (AP), the width of the compressed cord (W), the cross-sectional
      areas of the spine (A), the mean of the anteroposterior diameters of the cord at
      the levels of the adjacent cephalic and caudal vertebral bodies (AP), and the
      mean of the cross-sectional areas of the cord at the levels of the adjacent
      cephalic and caudal vertebral bodies (A) were measured on axial views from MRI.
      Paralysis of the posterior limbs occurred in this model when A/A became less than
      60%, AP/AP became less than 35% and AP/W became less than 20%. Pathological
      changes became apparent in the neural tissues when A/A became less than 50-60%,
      AP/AP became less than 25-30% and AP/W became less than 15%. Polyphasic wave
      forms were noted when A/A became less than 60%, AP/AP became less than 35% and
      AP/W became less than 20%. When the A/A became less than 40%, the
      histopathological changes became marked. SpEPs could no longer be detected at
      this degree of compression, indicating that all neural conduction had been
      blocked.

PMID- 8551100
TI  - [Effect of h-PTH on bone and bone marrow tissue in experimental osteopenia in
      rat].
AB  - We have evaluated changes in bone volume, bone marrow tissue, and the density of
      osteoclasts caused by intermittent administration of human parathyroid hormone (h
      PTH) to experimental osteopenia induced in rat by ovariectomy (OVX) or by
      diabetes mellitus (use of streptozotocin: STZ). A bone and marrow
      histomorphometric study was performed on HE-stained and tartrate-resistant acid
      phosphatase-stained (TRAP-stain) tibial bone sections. Retired Wistar rats, 7-8
      months old, were used. They were separated into the following nine groups; sham
      operated, base line control, vehicle administered, low or high dosage h-PTH
      administered OVX and STZ groups. 6.0 micrograms/kg/day of h-PTH (1-34) as a low
      dosage, and 60.0 micrograms/kg/day as a high dosage, was injected subcutaneously
      six times a week for 4 weeks from 9 weeks after ovariectomy or injection of
      streptozotocin. The bone volume decreased in both the OVX and STZ groups, while
      the fat tissue volume increased in the bone marrow in the OVX groups to
      compensate for this decrease, and the foamy marrow tissue volume increased in the
      STZ groups. The bone volume and the mean trabecular thickness in both the OVX and
      STZ groups increased by the intermittent administration of h-PTH, while the TRAP
      positive trabecular surface and the number of osteoclasts decreased. There was no
      significantly different bone changes between the low and high dosage groups. It
      is thought that the TRAP positive trabecular surface represented not only the
      active bone resorption surface but also the related contiguous uneroded surface.

PMID- 8551101
TI  - 0.3 keV carbon K ultrasoft X-rays are four times more effective than gamma-rays
      when inducing oncogenic cell transformation at low doses.
AB  - Oncogenic transformation and inactivation were investigated in C3H10T1/2 mouse
      embryo fibroblasts exposed to proton-induced 0.28 keV carbon K (CK)
      characteristic X-rays and 60Co gamma-rays as reference radiation at high dose
      rate (2-3 and 0.7 Gy/min respectively). Both oncogenic cell transformation and
      cell inactivation followed a linear-quadratic relationship with dose. At low
      doses where the linear component dominates CK ultrasoft X-rays were more
      effective, by a factor of 4, at inducing oncogenic cell transformation and cell
      inactivation compared with 60Co gamma-rays. For both endpoints the RBE of CK
      ultrasoft X-rays gradually decreased with increasing dose mainly due to the
      greater quadratic component for 60Co gamma-rays compared with CK ultrasoft X
      rays. Our experimental data are in agreement with the hypothesis that single DNA
      double-strand breaks (dsbs), which are induced by 0.28-keV ultrasoft CK X-rays,
      may lead to oncogenic cell transformation. With increasing absorbed dose, i.e.
      with decreasing mean distance between dsbs induced by 0.28-keV ultrasoft X-rays,
      oncogenic cell transformation and cell inactivation may also be induced by
      interaction between those dsbs.

PMID- 8551102
TI  - Enzymatic release of 5-formyluracil by mammalian liver extracts from DNA
      irradiated with ionizing radiation.
AB  - To identify a repair enzyme for 5-formyluracil (5-FU) caused by ionizing
      radiation in DNA, we used a radiolabelled product-release assay for this thymine
      damaged substrate. Double-stranded poly(dA-dT)-poly(dA-dT) was radiolabelled by
      nick translation with [2-14C]-thymidine triphosphate. The DNA was irradiated with
      X-rays and incubated with cell extract from mouse liver. Radiolabelled products
      released from the irradiated DNA into an ethanol-soluble fraction were analysed
      by reversed-phase hplc. Released 5-FU was detected as a free base during reaction
      with the cell extract. 5-Formyl-2'-deoxyuridine was not detected in the ethanol
      supernatant. Boiling the extract at 97 degrees C for 15 min completely abolished
      its ability to release 5-FU. Similar enzymatic activity was observed with rat
      liver extract. These results demonstrated that mammalian cells have enzymatic
      activity to release 5-FU from DNA.

PMID- 8551103
TI  - Irradiation-enhanced binding of carboplatin to DNA.
AB  - Carboplatin (3.6 mM) and salmon sperm DNA (3 micrograms), either double-stranded
      (dsDNA) or denatured single-stranded) (ssDNA), were irradiated (100 Gy) under
      hypoxic or oxic conditions. The drug and DNA were mixed either before, during, or
      after irradiation, and platinum binding to DNA was measured using atomic
      absorption spectrometry. Irradiation significantly increased the binding of
      carboplatin to dsDNA under hypoxic conditions, but did not increase the binding
      of carboplatin to ssDNA under similar hypoxic conditions. Irradiation did not
      result in an increased dsDNA-platinum binding under oxic conditions. When
      carboplatin was added to dsDNA immediately following irradiation of dsDNA, no
      increase in platinum binding was observed. When carboplatin and dsDNA were
      irradiated simultaneously but separately and then mixed there appears to be a
      slight increase in platinum binding, but it was not significant. Tetra
      ammineplatinum (II) chloride, a non-cytotoxic platinum compound, did not show an
      increase in platinum-DNA binding following irradiation under hypoxic conditions.
      The results suggest that radiation-enhanced carboplatin binding to DNA might be
      at least partly responsible for radiosensitization by carboplatin, especially in
      a cell line sensitive to carboplatin.

PMID- 8551105
TI  - RBE of fast neutrons for apoptosis in mouse thymocytes.
AB  - We compared apoptosis in mouse thymocytes following exposure to low doses of high
      linear energy transfer (LET), 62.5-MeV (p-->Be+) fast neutrons and low LET, 4-MeV
      photons by flow cytometric analysis of hypodiploid cells. The incidence of
      apoptotic cell death rose steeply at very low radiation doses reaching a plateau
      of 3 Gy. Both the time course and the radiation dose-response curves were similar
      for high and low LET radiation modalities. The relative biological effectiveness
      (RBE) of 1.0 for apoptosis in the mouse thymocyte system contrasts with the much
      higher value typically seen in many classical systems of clonogenic cell survival
      and tissue response. This difference suggests that while radiation-induced
      apoptosis may contribute significantly to loss of susceptible cells at doses of <
      or = 2 Gy, it appears to have a questionable role in determining the relative
      intrinsic radiosensitivity of mammalian cells to high and low LET irradiation at
      clinically relevant levels of cell kill.

PMID- 8551104
TI  - Radiosensitivity and effects of repair inhibitors for X-ray-induced chromosomal
      damage in mouse zygotes in S and G2 phases.
AB  - The potentiation effects of arabinofuranosyl cytosine (ara-C), hydroxyurea, 3
      aminobenzamide, and caffeine on the yield of chromosome aberrations were examined
      at the first-cleavage metaphase in mouse zygotes irradiated with X-rays in S and
      G2 phases (7.5 and 12 h after insemination respectively) in vitro. Potentiation
      effects were found in both S and G2 for all chemicals except ara-C. Caffeine
      completely released G2 arrest, which was not overcome by any other chemicals, and
      enhanced chromosome aberrations most effectively. Caffeine enhanced chromosome
      aberrations more in G2 irradiation than in S irradiation, and the frequency of
      chromatid-type aberrations was remarkably enhanced in G2 irradiation. The results
      in this study demonstrated an existence of two types of caffeine effects in the
      mouse zygotes irradiated in S and G2; a cancellation of G2 arrest and direct
      inhibition of DNA repair pathways. The chromosomal damage induced in G2 was
      effectively repaired by a repair pathway, which is affected by caffeine, on the
      other hand, the progression of cell cycle, not repair inhibition, was a major
      factor of caffeine effect on the yield of chromosome aberrations in S
      irradiation.

PMID- 8551106
TI  - Prediction of the initial slope of the acute clonogenic survival curve by the
      post-irradiation behaviour of cytochalasin-induced polykaryons.
AB  - We have investigated the behaviour of 11 lines of cultured cells in a survival
      assay whose endpoint is the ability of cells to become polyploid when incubated
      in the presence of cytochalasin B (CB). Single cells were induced by CB to form
      polykaryons after irradiation, and, by analogy with the colony-forming assay, the
      survival of polykaryon-forming units (PFUs) was defined as the fraction of cells
      able to achieve a given DNA content (at least 16C in most experiments). There was
      a radiation dose-dependent reduction in PFU survival, which, following the
      appearance of cells containing at least 16C DNA, was not markedly dependent upon
      the sampling time. In all cases, PFUs appeared to be more radioresistant than
      clonogens, especially at high dose. In 9/11 lines the PFU dose-response curves
      were exponential, while in two there was a pronounced curvature (quadratic
      parameter). There was a highly significant positive correlation between PFU
      response and the corresponding clonogenic initial slope. We suggest that in
      polykaryons the opportunity for the mechanical loss of DNA fragments may be
      reduced because the cells do not divide, and therefore that DNA damage resulting
      from chromosome aberrations may be less important in PFUs than in clonogens.
      Consequently, PFUs may express lesions not directly associated with mechanical
      gene loss. This assay may yield an alternative estimate for the clonogenic
      initial slope, and could be of use where colony-forming assays fail due to
      incomplete cell monodispersion.

PMID- 8551107
TI  - Variation in radiosensitivity due to cell age and split-dose recovery in
      polykaryons induced by cytochalasin.
AB  - We have investigated the properties of an in vitro cell survival assay that uses
      as its endpoint the ability to form polyploid cells (polykaryons) in the presence
      of cytochalasin B (CB). The criterion for survival is that a polykaryon-forming
      unit (PFU) must reach the arbitrary DNA content of at least 16C. The age
      dependence of PFU sensitivity to 137Cs irradiation was determined using V79-379A
      cells synchronized at mitosis. Cells assayed as PFUs demonstrated much less
      variation in radiosensitivity with age than did clonogens, but the changes in
      curve shape were qualitatively similar. In both assays mitotic cells yielded an
      exponential survival curve while that obtained at 5 h (mid-late S) had a marked
      quadratic component. Owing to the small overall variation in PFU survival with
      age, at doses greater than about 25 Gy the surviving fraction at 5 h was lower
      than in mitosis. In both V79-379A and HeLa S3 cells, PFUs demonstrated a capacity
      for split-dose recovery and yielded recovery ratios at 2.6 at 50 Gy in V79 and
      1.5 at 20 Gy in HeLa. Since these ratios were much lower than in clonogens at the
      same dose, we suggest that this is consistent with an association that we have
      previously demonstrated between PFU response and the clonogenic initial slope. In
      an attempt to clarify the DNA lesions to which PFUs may be sensitive, we
      determined PFU response following exposure to 254-nm UV irradiation. In contrast
      with ionizing radiation, PFU response to UV was very similar to that of
      clonogens. This suggests that following UV exposure the absence of cytokinesis in
      polykaryons may confer less protection than in the case of ionizing radiation,
      possibly due to fundamental differences in the spectrum of DNA lesions produced.

PMID- 8551108
TI  - Distribution of 210Pb at endosteal surfaces of bone from Canadian Arctic caribou.
AB  - Alpha particle energy spectra were measured at femoral endosteal surfaces of
      Canadian Arctic caribou (Rangifer tarandus) to assess the profile of
      concentration with depth of 210Po supported by 210Pb. Femur samples from five
      caribou all showed a pronounced superficial concentration of 210Po, in a layer
      1.9 - 6.4 microns thick. Within this layer 210Po was concentrated 1.5 - 10 times
      with respect to diffuse volume-distributed 210Po. This result is consistent with
      an earlier study of 210Po at human cranial bone surfaces, which showed 210Po to
      be concentrated about four times in a surface layer <3 microns thick. However,
      the present results have higher precision than the human bone data due to the
      much greater concentration of 210Pb and 210Po in caribou bone. The validity of
      using 210Po as a marker of 210Pb, and the in vivo 210Po/210Pb ratio are
      discussed. As a result of the measured endosteal superficial concentration of
      210Po in caribou, the alpha particle dose was calculated to be enhanced by a
      factor of 1.06 - 1.96 (mean 1.48) for bone lining cells, and of 1.08 - 2.39 (mean
      1.69) for soft tissue above the bone surface, assuming equilibrium between 210Pb
      and 210Po. It is suggested that an additional longer-lived compartment for bone
      surface lead could be incorporated into bio-kinetic models for lead.

PMID- 8551109
TI  - Efficacy of 3,4,3-LIHOPO for enhancing the excretion of plutonium from rat after
      simulated wound contamination as a tributyl-n-phosphate complex.
AB  - The siderophone analogue 3,4,3-LIHOPO, referred to hereafter as LIHOPO, has been
      examined for its ability to remove 238Pu in a tributyl-n-phosphate (TBP) complex
      from rat after intramuscular (i.m.) or subcutaneous (s.c.) contamination. The
      chelating agent was administered at a dosage of 30 mumol.kg-1, 30 min after the
      contamination, either by intravenous (i.v.) or local injection. By day 7 after
      exposure, local (i.m.) administration of LIHOPO reduced the amounts of i.m.
      injected 238Pu in the would site, skeleton and liver to 75, 20 and 25%
      respectively of those in untreated animals. At the i.m. Pu would site, local
      treatment was superior to i.v. treatment; both ligands were equally effective. At
      the s.c. Pu would site, local and systemic treatments were equally effective and
      LIHOPO was superior to DTPA. After translocation, LIHOPO was the most effective
      treatment for enhancing Pu excretion, whatever the route of contamination and
      treatment: the administration of LIHOPO and DTPA reduced whole-body Pu retention
      by a factor of 1.8 and 1.4 respectively. All these results are encouraging for
      the use of LIHOPO in the future but more studies are needed, concerning both the
      toxicity of the compound and its use in man.

PMID- 8551110
TI  - Fat cells in red bone marrow of human rib: their size and spatial distribution
      with respect to the radon-derived dose to the haemopoietic tissue.
AB  - Samples of human rib were collected at autopsy and 20 were selected for marrow
      fat cell measurement, representing an age range of 16-96 years. The mean diameter
      of fat cells in red bone marrow of human rib was found to increase from around 48
      microns at ages 16-29 years to around 65 microns at ages 82-96 years. There was a
      greater number of fat cells of smaller size range in younger ages compared with
      that in older ones. The maximum size of fat cells was found to be 102 microns.
      Calculated radon-derived doses to haemopoietic tissue ranged from 60 to 162
      microSv y-1 at average UK exposures of 20 Bq m-3. It was concluded that the bone
      marrow fat fraction is the important parameter as far as alpha-radiation dose
      from radon in fat is concerned. This updates the theoretical estimates of dose
      carried out by Richardson et al. (1991).

PMID- 8551111
TI  - Long-term effects on tumour incidence and survival from 241Am exposure of the
      BALB/c mouse in utero and during adulthood.
AB  - BALB/c mice were given 100, 500 or 1500 Bq/g 241Am at day 14 of pregnancy. The
      offspring were separated from the mothers at birth and followed until death. In
      addition, adult females and one group of males were also studied for the effects
      of 241Am following treatment with 45-213 Bq/g. Adults treated with 241Am showed
      significantly shortened survival and increased incidence of osteosarcoma (to 40 -
      50%). The data also suggest that the female mouse is more susceptible to
      induction of osteosarcoma than the male. There was also a significant increase in
      osteosarcoma, all bone tumours, all sarcomas, and all leukaemias in the offspring
      from the contaminated mothers, although this appeared to occur independently of
      dose. Calculations of the number of osteosarcomas induced per Gy varied for
      contamination of adult mice between 0.2 and 0.01 and for the offspring between 6
      and 0.6. Thus, offspring seemed to be about 10 times more at risk if
      osteosarcomas induced per mouse Gy are compared. Surprisingly, offspring from
      mothers treated with 241Am displayed a longer survival time than controls,
      possibly due to fewer deterministic lung diseases appearing early in life.

PMID- 8551112
TI  - Increased c-fos expression associated with hyperthermia-induced apoptosis of a
      Burkitt lymphoma cell line.
AB  - Hyperthermia (42 - 44 degrees C for 30 min to 1 h) can induce apoptosis in a
      variety of cell types and tumour cell lines. This process is usually, but not
      invariably unaffected by RNA and protein synthesis inhibition. C-fos expression
      has been implicated in the regulation of apoptosis occurring under diverse
      circumstances. By heating the Burkitt lymphoma cell line, BM 13674, for 43
      degrees C for 30 min, approximately 60% of cells underwent apoptosis within 6h of
      treatment. Co-ordinate with the massive induction of apoptosis, a 10-fold
      increase in the steady state c-fos mRNA expression occurred.

PMID- 8551113
TI  - Human natural killer cytotoxic activity is not affected by in vitro exposure to
      50-Hz sinusoidal magnetic fields.
AB  - Epidemiological studies have suggested, but not demonstrated, a role of exposure
      to 50/60-Hz magnetic fields in increasing cancer risk in man (workers and the
      general population). A possible target of magnetic fields is the immune system.
      In particular, it is known that an important defence against cancer is
      represented by natural killer (NK) cells capable of killing cancer cell targets.
      To test this hypothesis, human NK cells, stimulated or not with
      phytohaemagglutinin or interleukin 2, were exposed to 50-Hz sinusoidal magnetic
      fields before or during the cytotoxicity test, and then mixed with a variety of
      target cancer cell lines (Daudi, Raji, U937, H14, IGROV, SW626, K562, HL60). The
      experiments were performed in two laboratories (Rome and Modena) by means of two
      different exposure systems. The results of both laboratories suggest that 50-Hz
      sinusoidal magnetic fields with flux densities up to 10 mT do not affect the
      cytotoxic activity of human NK cells.

PMID- 8551114
TI  - Evolution of quality of life assessment in head and neck cancer.
AB  - Quality of life assessment as part of clinical practice in head and neck oncology
      began over 40 years ago. Early studies were narrative and cross-sectional; these
      were followed, at first, by simple quantitative measures of various parameters
      and later by longitudinal studies of greater complexity. More recently quality of
      life has been employed in a randomized clinical trial of head and neck cancer.
      Quality of life has evolved to become a standard means of assessing clinical
      outcomes, and an accepted end point measurement in clinical trials, to be
      considered alongside survivorship and side effects/complications.

PMID- 8551115
TI  - Can ear irrigation cause rupture of the normal tympanic membrane?: an
      experimental study in man.
AB  - Rupture of the tympanic membrane (TM) during ear irrigation is a rare but unhappy
      event. In this study the maximum overpressures obtained in the deep part of the
      external auditory meatus (EAM) during ear irrigation were measured postmortem in
      20 cadavers. The highest pressures were obtained in normal- or wide-dimension
      EAMs when a metal syringe was used. With this device, the median maximum
      overpressure was 240 mmHg (range 200-300 mmHg). Experiments with simulation of an
      obturating wax plug did not increase the maximum overpressure. Compared with the
      lowest overpressures which can rupture TMs the pressures measured in this study
      were insufficient to rupture normal TMs but sufficient to rupture atrophic TMs
      with the lowest tensile strength. This finding may have medicolegal implications.

PMID- 8551117
TI  - Bone pate repair of the eroded incus--five years on.
AB  - Seventy-four patients undergoing bone pate repair of the long process of the
      incus as part of a tympanoplasty are presented. Mean follow-up time was 66 months
      (range 12-143 months). Hearing results are averaged over the frequencies 500,
      1000, 2000 and 4000 Hz. Thirty-two per cent of the patients had hearing
      thresholds better than 30 dB pre-operatively. A significant improvement in
      hearing was seen (p < 0.001). The data were also analysed to assess the effect of
      the pre-operative state of the tympanic membrane on the final result. The pre
      operative condition of the tympanic membrane was either perforated (35 ears) or
      atrophic (33 ears). Six tympanic membranes were intact but these were excluded
      from the final results. No difference in hearing result was found between
      patients who had an ossicular repair in combination with either a perforated
      tympanic membrane repair or an atrophic membrane repair. Average hearing gain in
      the perforated group was 13 dB, in the atrophic group 9 dB and in the intact
      group 7 dB.

PMID- 8551116
TI  - Comparison of the repair of permanent tympanic membrane perforations by
      hydrocolloidal dressing and paper patch.
AB  - Thirty consecutive patients with permanent perforations of their tympanic
      membranes (TM) present from 2.5 to 50 years (mean 18.7 years) were admitted to a
      prospective study using two alternative methods of dressings for closure of the
      perforations. An adhesive-coated hydrocolloid material was compared with a
      conventional dressing of vaseline impregnated rice paper patch after de
      epithelialization of the perforation border. Nine of the permanent TM
      perforations (30 per cent), five with the hydrocolloidal dressing and four with
      the rice paper patch had healed when followed-up after one year. The size of
      eight of the central perforations that had healed was equal to or less than 25
      per cent of the TM. Also one perforation with a size of 65 per cent had healed.
      Seven perforations were located in the posterior part of the TM: four in the
      posterior-superior quadrant, one in the inferior quadrant, one had engulfed the
      posterior half of the TM and one included the anterior-inferior quadrant. Only
      two perforations out of 14, with a size of 25 per cent or less, located in the
      anterior-inferior quadrant, healed. No significant difference was demonstrated
      between the two types of dressings. Both groups noted an immediate improvement in
      hearing of 10.8 and 9.3 dB, respectively, after application of the dressing. The
      study demonstrates that application of an occlusive dressing or paper patch in 30
      per cent of patients can promote the healing of long-standing perforations. The
      chances for healing are better if the perforation is located in the posterior
      part of the TM. This simple technique immediately improved hearing and should be
      tried before a patient is referred for myringoplasty surgery.

PMID- 8551118
TI  - Localization of active otosclerotic foci by tympano-cochlear scintigraphy (TCS)
      using correlative imaging.
AB  - High-resolution, tympano-cochlear scintigraphy (TCS) is a useful tool for
      visualizing changes in labyrinthine bone metabolism in active otosclerosis in
      vivo. But until now, the activity patterns have mostly been rather imprecisely
      ascribed to the labyrinthine structures; more exactly by means of high-resolution
      CT (HR-CT). Experimental studies on TCS using a human temporal bone model
      revealed that correlative imaging of X-ray photographs and the scintigrams or
      superimposition with masks of the temporal bone drawn from the X-rays can
      facilitate the localization of small foci of about 0.5-1 mm. Clinical
      applications of the visualization technique, combining functional with structural
      images, confirmed the benefit of this method, improving the accuracy in detection
      and localization of focal activity enrichment of the petrous bone in cases of
      active otosclerosis by means of TCS.

PMID- 8551119
TI  - Charing Cross CT protocol for endoscopic sinus surgery.
AB  - The Charing Cross computerized tomography protocol for imaging the paranasal
      sinuses uses 2 mm thick slices with table increments of 8 mm: 10 to 12 coronal
      and two axial images are produced. These provide the necessary information for
      diagnosis of chronic rhinosinusitis and safe endoscopic sinus surgery. The
      technique is quicker and cheaper than previously described protocols and exposes
      the lens of the eye to less radiation.

PMID- 8551120
TI  - Intracranial complications of sinusitis: the need for aggressive management.
AB  - Sinus-induced intracranial sepsis can represent a genuine medical and surgical
      emergency. We review 12 cases presenting to our hospitals over a five-year
      period. Nine were male and three were female with an age range of 16 to 74 years
      (mean 35.5 years). Four patients had their sinusitis diagnosed prior to admission
      and eight did not. Nine patients had bilateral sinus disease, the most common
      sinus involved was the frontal followed by the ethmoid, maxillary and sphenoid.
      Neurosurgical drainage was via a craniotomy in seven cases and burr hole in
      three. Nine patients underwent sinus surgery and three did not. Of the nine who
      had sinus surgery three had frontal drainage, four fronto-ethmoidal and two trans
      sphenoidal drainage. The most common organism was Streptococcus milleri. Our
      series confirms that sinus-induced intracranial sepsis is a serious problem
      needing early diagnosis and aggressive treatment. We would recommend a high index
      of suspicion of sinusitis in patients with intracranial infection.

PMID- 8551121
TI  - Analysis of recurrence after surgical treatment of advanced laryngeal carcinoma.
AB  - The pattern of recurrences after surgical treatment of 276 patients with stage T3
      and T4 laryngeal carcinoma was reviewed. Nodal recurrence was the commonest site
      and occurred mainly in patients with supraglottic and transglottic carcinoma.
      Distant metastasis was the second commonest site of recurrence, and the most
      distant metastases developed without locoregional recurrence. Local recurrence
      alone was uncommon in patients treated with primary surgery.

PMID- 8551122
TI  - Provox valve use for post-laryngectomy voice rehabilitation.
AB  - The Provox voice prosthesis has been used in our department since September 1992
      for post-laryngectomy voice rehabilitation. This prosthesis is an indwelling low
      resistance tracheoesophageal valve. The cohort consisted of 28 laryngectomes with
      a mean follow-up time of 352 days. The average valve life before failure was 148
      days. Speech intelligibility of 85 per cent was achieved for complete sentences.
      No major surgical problems were associated with the valve insertion or its use.
      Replacement of the prosthesis as an outpatient procedure was accomplished without
      difficulty.

PMID- 8551123
TI  - Treatment of head and neck cancer with photodynamic therapy: results after one
      year.
AB  - Photodynamic therapy (PDT) is a new and promising treatment modality for the
      treatment of malignant disease. This paper reports the preliminary experience of
      our group in the use of this therapy for the treatment of tumours arising in the
      head and neck. The majority of treatments in these cases have used a second
      generation systemic photosensitizer, meta-tetrahydroxyphenylchlorin (m-THPC). Two
      other cases were treated with either Photofrin 2 (a first generation systemic
      sensitizer) or with the topical photosensitizer, delta-aminolaevulinic acid
      (delta-ALA). The initial results have been encouraging with good clinical
      responses evident in patients presenting with a variety of differing tumour
      types. We feel there is now sufficient evident of the efficacy of this treatment
      to warrant a multicentre prospective study into the treatment of early head and
      neck cancer with PDT.

PMID- 8551124
TI  - Flexible endoscopic tracheo-oesophageal puncture under local anaesthetic.
AB  - Blom-Singer valve prosthesis is an increasingly popular technique for voice
      rehabilitation in alaryngeal patients. Although primary voice puncture is being
      practised, the creation of the tracheo-oesophageal fistula is performed in the
      majority of patients as a secondary procedure. We describe a technique of
      secondary tracheo-oesophageal puncture using the flexible endoscope which can be
      performed under local anaesthetic and sedation. The technique overcomes the
      difficulty of passing a rigid oesophagoscope or forceps to the level of the
      tracheostome in a scarred and irradiated neck. The new technique also obviates
      the need for general anaesthesia. We have successfully used the technique in
      three patients.

PMID- 8551125
TI  - Two cases of otolaryngeal tuberculosis in a Danish married couple.

PMID- 8551126
TI  - Complicated suppurative otitis media in a Greek diver due to a marine halophilic
      Vibrio sp.
AB  - Halophilic vibrios are distinct from non-cholera vibrios and have been recognized
      increasingly as potentially pathogenic bacteria in extraintestinal infections. A
      case of suppurative chronic otitis media in a Greek diver with Vibrio
      alginolyticus recovered from an ear drainage culture, is reported. The patient
      received appropriate antimicrobial therapy and her hearing improved significantly
      after a tympanoplasty type I was performed. The association of halophilic Vibrio
      spp. infections with prolonged seawater contact, particularly in subtropical
      climates, is discussed. In swimmers with extensive exposure to salt water,
      individual preventive measures and aetiological treatment of ear infections seems
      to be required in order to reduce the severity of possible Vibrio spp. ear
      infections.

PMID- 8551127
TI  - An unusual case of deafness with speech impairment: lesson in diagnosis and
      management.
AB  - Hearing impairment can be the cause of significant disability and handicap. This
      medico-legal case demonstrates the need for accurate assessment of both the
      severity and type of hearing loss if the best clinical management is to be
      provided. In particular, the case identifies the critical role of additional,
      objective auditory testing when pure tone audiometry, which depends on the
      subjective response of the individual, is inconsistent or indicates severe
      hearing impairment.

PMID- 8551128
TI  - VIIIth cranial nerve involvement in sarcoidosis.
AB  - Hearing loss and vertigo are uncommon but well-recognized complications of
      neurosarcoidosis. Until recently the site of the lesion has been debatable and
      the efficacy of steroids commonly prescribed for this type of hearing loss has
      been said to be doubtful. A case is presented of sarcoidosis-induced hearing loss
      in which bilateral VIIIth nerve lesions were demonstrable by MRI with gadolinium
      enhancement. Treatment with high-dose steroids and azathioprine produced a
      symptomatic improvement and virtual resolution of the lesions.

PMID- 8551129
TI  - Latex-induced allergic rhinitis in a laboratory nurse.
AB  - A case of occupational rhinitis in association with natural rubber latex
      hypersensitivity is presented. In the nasal provocation test for natural rubber
      latex glove powder the nurse experienced rhinorrhoea. A significant increase in
      the amount of nasal secretion and mucosal oedema could be detected. The patient
      also showed a positive skin prick test to natural rubber latex allergens, and an
      elevated natural rubber specific IgE level in her serum. This, to our knowledge,
      has not been previously reported in the literature.

PMID- 8551130
TI  - Air gun pellets in the sinuses.
AB  - Three cases of penetrating sinus injuries due to air gun pellets are presented in
      order to illustrate the potentially serious consequences of air gun injuries.
      Primary surgery was performed in all cases. The clinical presentation, methods of
      accurate pre-operative localization and surgery are discussed.

PMID- 8551131
TI  - Osteogenic sarcoma of sphenoid bone: an extended lateral skull base approach.
AB  - Osteogenic sarcoma involving the sphenoid bone is an extremely rare condition.
      The rarity of the disease and the close proximity of the sphenoid bone to the
      various important intracranial structures poses a real challenge in diagnosis and
      surgical management of these lesions. An extended lateral craniofacial resection
      by a multidisciplinary approach was carried out in one such case to attempt en
      bloc resection. This case is presented and also a review of the relevant
      literature.

PMID- 8551132
TI  - Paradoxical vocal fold movement: a case report.
AB  - Paradoxical vocal fold movement leads to marked inspiratory stridor with
      adduction of the vocal folds on inspiration. A patient is presented who
      illustrates some of the difficulties in diagnosis and management. A range of
      treatments were tried including tracheostomy, laser arytenoidectomy and vocal
      fold lateralization.

PMID- 8551133
TI  - Right vocal fold paralysis as a result of central venous catheterization.
AB  - Invasive peri- and post-operative monitoring is being increasingly utilized, and
      a corresponding increase of concomitant complications are becoming apparent. Two
      cases of complete right vocal fold paralysis are reported as a possible
      complication of right central venous catheterization. The underlying aetiology of
      this complication is presumed to be either direct trauma at the time of
      introduction of the central venous catheter, or by thrombosis and fibrosis around
      the recurrent laryngeal or vagus nerve. It is suggested that multiple attempts at
      cannulation and leaving the central line in situ for long periods increases the
      risk of this complication. When the integrity of the left recurrent laryngeal
      nerve or vagus is jeopardized or must be sacrificed during surgery, it is
      suggested that ipsilateral central lines are inserted to minimize the risk of
      bilateral vocal fold paralysis. Cases of vocal fold paralysis secondary to
      central line insertion should be followed expectantly and surgical intervention
      only be considered after 12 months review.

PMID- 8551134
TI  - Highly aggressive behaviour of occult papillary thyroid carcinoma.
AB  - Occult papillary thyroid carcinoma is generally associated with an excellent
      prognosis. Distant metastasis of this tumour is extremely rare. A case of occult
      papillary thyroid carcinoma with metastases to the lungs, cervical lymph nodes,
      skeleton, and the brain is reported. The tumour expressed itself in extremely
      aggressive clinical behaviour and responded only partially to aggressive therapy.
      The controversial methods of treatment for occult papillary thyroid carcinoma are
      also discussed.

PMID- 8551135
TI  - Acute Sjogren-like syndrome as the first manifestation of a generalized CMV
      infection in a patient with AIDS.
AB  - We report the first case of generalized cytomegalovirus (CMV) disease in an AIDS
      patient who presented with an acute Sjogren-like syndrome and was diagnosed by
      parotid gland biopsy. All symptoms disappeared after a few days of intravenous
      ganciclovir therapy.

PMID- 8551136
TI  - Magnetic resonance imaging after frontal sinus surgery with fat obliteration.
AB  - The obliteration of the frontal sinus via an osteoplastic approach is performed
      with the aim of achieving a permanent 'switching off' by final and conclusive
      clearing out. For this, freshly harvested abdominal fat has shown itself to be
      the best clinically. It is possible to demonstrate the vitality of fat
      transplanted into the frontal sinus without an operation, i.e. by a macroscopical
      and histological examination using magnetic resonance imaging (MRI). The magnetic
      resonance examinations were carried out on a supraconductive 0.5 T Magnet
      (Gyroscan T.S.II, Philips Medicine Systems, Eindhoven, Netherlands) with a
      quadrature (square) head spool. We produced T1-weighted spin echo images (TR: 450
      550 ms; TE: 20-25 ms), T2-weighted fast spin echo images or in double-echo
      technique in transverse orientation (Turbo SE or TR: 2000-2500 ms; TE: 50-90 ms)
      and short tau inversion recovery (STIR) sequences for fat suppression (TJ: 140
      ms; TR: 1400 ms; TE: 30 ms). The fat implanted into the frontal sinus of 11
      patients aged 22-65 years, having undergone an osteoplastic frontal sinus
      operation with obliteration, was examined post-operatively by MRI. Objectives
      were the time-dependent distribution of portions of vital fatty or connective
      tissue, the eventual development of necroses or cysts as well as recurrences,
      inflammatory complications or re-epithelization of the frontal sinus four to 24
      months post-operatively. In only six out of 11 cases was vital fatty tissue
      found. Fatty necrosis occurred five times, whereas in four cases a transformation
      into granulation tissue and in one case into connective tissue could be seen. All
      11 patients were complaint-free. Long-term observations are needed to see if
      differences in the recurrence rate of frontal sinus disease are dependent on
      whether the implanted fat remains vital or necrosed and transformed.

PMID- 8551137
TI  - Giant cell reparative granuloma of the cricoid cartilage.
AB  - Giant cell reparative granuloma (GCRG) is an uncommon benign lesion which has
      been reported at several sites in the head and neck. We present a case of a GCRG
      of the cricoid cartilage not previously described in the literature. It must be
      differentiated from the brown tumour of hyperparathyroidism and true giant cell
      tumours of bone. These were excluded on clinical, biochemical, radiological and
      histological grounds. The lesion responded well to surgical debulking and
      curettage and the patient remained disease-free 15 months after treatment.

PMID- 8551138
TI  - Papillary carcinoma arising in a thyroglossal duct cyst: a case report and
      literature review.
AB  - Papillary carcinoma arising in a thyroglossal duct cyst is a rare finding. Less
      than 100 cases have been reported in the English literature. In most cases the
      diagnosis is only established after excision of a clinically benign thyroglossal
      duct cyst. The aetiology of such tumours is unclear but de novo origin and spread
      from a primary thyroid gland tumour has been suggested. This has important
      implications for therapeutic approaches. A further case of thyroglossal duct
      carcinoma is presented and the management is discussed on the basis of the
      current rationale for treatment of thyroid cancer.

PMID- 8551139
TI  - Thyroid metastasis from nasopharyngeal carcinoma: a case report.

PMID- 8551140
TI  - The diagnosis of inflammatory sinonasal disease.

PMID- 8551141
TI  - Time to think about nurses in ENT.

PMID- 8551142
TI  - The clinical significance of the communicating branches of the somatic sensory
      supply of the middle and external ear.
AB  - The sensory supply of the middle and external ear is complicated by multiple
      neural communications. The anatomy of these communications and their clinical
      significance will be described in this paper.

PMID- 8551143
TI  - Comparison of the proteins of middle ear effusion with human mast cell proteins.
AB  - In order to clarify the role of mast cells in the aetiology of secretory otitis
      media (SOM), we compared the protein components of middle ear effusion (MEE) with
      human mast cells using acrylamide gradient gel electrophoresis and
      electrofocusing methods. This first direct comparison between the proteins of MEE
      and human mast cells has been made possible by a method developed in our
      laboratory for cultivation of human mast cells in tissue culture. On
      electrophoresis, we found that out of 12 bands of MEE proteins that were
      different from the serum, seven (58 per cent) had a similar electrophoretic
      migration rate (Rx) to mast cells. On electrofocusing, three of the four bands of
      MEE had a similar Rx to the mast cells. We have shown that proteins of mast cells
      and MEE had similar Rxs. Therefore, our study supports previous studies which
      suggests that mast cells play an important role in the aetiology of SOM.

PMID- 8551144
TI  - Long-term ventilation of the middle ear using a tympanotomy technique.
AB  - The technique of long-term middle ear ventilation using a tympanotomy technique
      is presented. This has proved successful in the management of persistent middle
      ear effusion despite numerous previous short- and intermediate-term tympanic
      membrane ventilation tubes. The technique is particularly appropriate in the
      presence of severe tympanosclerosis as a result of previous tympanostomy tubes,
      posterior tympanic membrane collapse and adhesion, and atelectasis.

PMID- 8551145
TI  - Tympanic neurectomy in the management of parotid sialectasis.
AB  - The term sialectasis refers to dilation of the salivary ducts. Parotid
      sialectasis presents itself as recurrent painful swellings during mastication
      and/or swallowing. Our results with 10 cases treated by tympanic neurectomy over
      a period of nine years, from 1983 to 1992, were encouraging as seven cases had
      improvement of their symptoms. Anatomy of the tympanic plexus and surgical
      procedure are discussed as well as a review of the literature. We recommend
      extensive interruption of the secreto-motor nerve fibers by thoroughly drilling
      into the hypotympanum and below the basal turn of the cochlea. We also recommend
      that this be carried out by an experienced otologist to avoid possible
      complications.

PMID- 8551146
TI  - Antimicrobial management of chronic sinusitis in children.
AB  - This study retrospectively investigated the microbiology and management of 40
      children who suffered from chronic sinusitis. The sinuses infected were the
      maxillary (15 cases), ethmoid (13), and frontal (seven). Pansinusitis was present
      in five patients. All aspirates were cultured for aerobic and anaerobic bacteria.
      A total of 121 isolates (97 anaerobic and 24 aerobic) were recovered. Anaerobes
      were recovered from all 37 culture-positive specimens, and in 14 cases (38 per
      cent) they were mixed with aerobes. Twenty-three beta-lactamase-producing
      bacteria were isolated from 16 (43 per cent) patients. The 15 patients who
      received clindamycin had the most rapid response to therapy and a change of
      therapy and surgical drainage was required in one case. Of the 16 patients who
      received amoxycillin or ampicillin, 16 responded to therapy, six needed a change
      of therapy, including four who also had surgical drainage. Of the six who were
      treated with erythromycin, three needed antibiotic change, two with surgical
      drainage. Of the three that received cefaclor, two were cured, and one had an
      antibiotic change. Resistant organisms were recovered in all the cases that
      required therapeutic change. These findings support the important role of
      anaerobic bacteria in the polymicrobial cause of chronic sinusitis in children,
      and the superiority of therapy effective against these organisms.

PMID- 8551147
TI  - Sleep nasendoscopy: what benefit to the management of snorers?
AB  - It has been proposed that sleep nasendoscopy (SN) will improve the success rate
      of the uvulopalatopharyngoplasty operation by identifying those patients with
      palatal snoring. The aim of this study was to test the efficacy of SN in the
      management of snorers who do not have obstructive sleep apnoea. This study
      compared a group of 26 snorers managed without SN (group A) to a group of 27
      snorers managed with SN (group B). The post-operative results of group A were 61
      per cent cured, 27 per cent better and 8 per cent unchanged. Group B results were
      76 per cent cured, 19 per cent better and 5 per cent unchanged. However, if
      patients with only palatal snoring had surgery, the results for group B would
      have been 94 per cent cured, 6 per cent better and 0 per cent unchanged (95 per
      cent C.I. of difference +0.14, +0.54, p = 0.017). The results confirm the
      predictive power of SN in identifying success following
      uvulopalatopharyngoplasty. A simple grading system is suggested to aid in
      treatment planning. Patients are divided into three categories on SN: palatal
      snorers, mixed snorers and non-palatal (tongue base) snorers. It is proposed that
      uvulopalatopharyngoplasty may cure palatal snorers but mixed snorers will need
      additional therapies to eliminate their snoring although
      uvulopalatopharyngoplasty may improve the symptoms.

PMID- 8551148
TI  - Would day-case adult tonsillectomy be safe?
AB  - Day-case surgery is increasing to improve health care efficiency. Adult
      tonsillectomy is performed on an inpatient basis in the UK because of safety
      concerns regarding primary haemorrhage. This study aims to investigate the likely
      safety of day-case tonsillectomy in adults, by defining the incidence and timing
      of primary haemorrhage and therefore to establish a safe time period for same-day
      discharge. Prospectively recorded data on 2,157 adult tonsillectomies over a five
      year period were reviewed. Serious primary haemorrhage was uncommon (0.8 per
      cent). The 95 per cent reference range of time to primary haemorrhage was within
      0 to 6.8 hours of surgery and the 95 per cent confidence interval (C.I.) of its
      upper limit was 5.2 to 8.4 hours. The results compare favourably with the UK
      inpatient and US adult day-case literature. We conclude that day-case
      tonsillectomy would probably be safe in adults if the patients are discharged
      after 8.4 hours.

PMID- 8551149
TI  - Pharyngeal trauma in children--accidental and otherwise.
AB  - Pharyngeal perforation is an uncommon injury in children. Most reported cases to
      date have been secondary to instrumentation or penetrating wounds. Laceration to
      the pharyngeal wall may introduce air, secretions and bacteria into the
      parapharyngeal space and mediastinum and consequently has potentially life
      threatening sequelae. The management of these injuries is controversial. We
      present a series of four children who suffered pharyngeal trauma, accidentally
      and otherwise, and discuss their management. We recommend a high index of
      suspicion of pharyngeal injury in all cases of oropharyngeal trauma and overnight
      admission to hospital for observation until an accurate diagnosis has been
      established. Non-accidental injury of the child must be seriously considered in
      all cases.

PMID- 8551150
TI  - Management of carotid artery exposure with pectoralis major myofascial flap
      transfer and split-thickness skin coverage.
AB  - The risk for post-operative exposure of the carotid artery due to skin flap
      necrosis after major head and neck surgery is increased after previous radiation
      and in severely malnourished patients. Eight patients are described who presented
      with an (imminent) carotid exposure one to eight weeks after surgery. Pectoralis
      major myofascial flap transfer with split thickness skin graft coverage was used
      for protection of the carotid artery. All cases were managed successfully and
      healed primarily in two to four weeks with acceptable cosmesis. We advocate
      immediate treatment in the event of an exposed carotid (or imminent exposure) by
      a pectoralis major myofascial flap with split-thickness skin grafting.

PMID- 8551151
TI  - Measurement of small tissue volumes using Holden's apparatus.
AB  - A reproducible method for the estimation of volumes of small tissue samples was
      needed to allow comparison of the biological activity of tissue explants and to
      relate symptom improvement to procedures such as adenoidectomy or polypectomy.
      Holden's apparatus, which utilizes fluid displacement between two chambers, was
      compared to displacement in a 20 ml syringe. Two observers made four readings
      each on 20 tissue samples (range 0.37 to 4.70 ml) using both methods for
      comparison. A two-way analysis of variance for replicated data gave an F ratio of
      0.6885 (df = 19; p > 0.8) for Holden's apparatus, and an F ratio of 1.4307 (df =
      19; p > 0.1) for the 20 ml syringe. The standard error of the mean for repeated
      readings on the same sample by an observer was 0.001 ml for Holden's apparatus
      and 0.014 ml for the syringe method. For accurate estimation of small tissue
      volumes within 0.01 ml we recommend Holden's apparatus.

PMID- 8551152
TI  - How we do it: use of a venous cannulation needle for endoscopic Teflon injection
      to the vocal folds.
AB  - Since its introduction in the 1960's the injection of Teflon into a paralysed
      vocal fold has become a standard treatment in laryngology. Although in recent
      years alternative treatments have been suggested, such as the injection of
      collagen or autogenous fat (Mikaelian et al., 1991), re-innervation procedures
      and thyroplasty (Crumley, 1990), the use of Teflon is still widespread (Rontal
      and Rontal, 1991; Dedo, 1992). Various instruments have been developed for the
      application of Teflon paste and these take the form of a gun-like syringe with a
      ratchet mechanism. For a number of years we have injected Teflon using a needle
      marketed for internal jugular vein cannulation along with a plastic 1 ml syringe
      thus making substantial savings to our department in terms of both time and cost.

PMID- 8551153
TI  - Unilateral hearing loss due to a rhabdomyoma in a six-year-old child.
AB  - A case report of a six-year-old child is presented, who had had a unilateral
      sensorineural hearing loss for several years. Because of impairment in the ABR as
      well as in the caloric testing a MRI and CT scan were performed. A 17 mm tumour
      in the cerebellopontine angle (CPA) was detected, which after suboccipital
      surgery proved to be a rhabdomyoma. This tumour has not been described before in
      the CPA. Unilateral sensorineural hearing loss should, at all ages, be an
      indication for further (radiodiagnostic) investigations.

PMID- 8551154
TI  - Leiomyomatous hamartoma of the posterior tongue: a case report.
AB  - A case of a rare leiomyomatous hamartoma arising in the posterior tongue of a
      sixteen-month-old male is reported. There has been no recurrence following simple
      excision and presenting symptoms of choking on swallowing have resolved. Most
      other leiomyomatous hamartomas in the upper aerodigestive tract have been
      reported in Japanese patients and have involved the maxillary gingiva and hard
      palate.

PMID- 8551155
TI  - Endobronchial tuberculosis masquerading as foreign body aspiration.
AB  - Endobronchial tuberculosis is a rare manifestation of pulmonary mycobacterial
      disease. We present a case in which an endobronchial tuberculous granuloma
      resulted in acute respiratory distress simulating foreign body aspiration.

PMID- 8551156
TI  - Dysphonia as an atypical presentation of gastro-oesophageal reflux.
AB  - We present three cases of dysphonia in which gastro-oesophageal reflux (GOR)
      appeared to be a precipitating factor. In all cases reflux was clinically occult.
      We discuss the theory and implications of GOR presenting atypically with
      laryngeal symptoms, and outline our current approach to laryngeal symptoms of
      clinically evident or occult GOR.

PMID- 8551157
TI  - Stridor in patients with HIV infection.
AB  - The immunodeficiency which results from HIV infection is associated with a range
      of opportunistic infections and tumors which may present with the symptoms of
      upper airways disease. This paper presents three cases of stridor from different
      causes in patients with HIV infection, all of whom recovered following treatment.
      The management of this problem requires consideration of the likely aetiology
      which, in those with advanced immunodeficiency, includes bacterial and fungal
      laryngitis and epiglottitis as well as rapidly growing laryngeal tumours.
      Recommendations for the treatment of those with HIV infection who present with
      severe or rapid-onset stridor should include a combination of aggressive airway
      intervention and broad-spectrum antibacterial and antifungal agents. Laryngeal
      biopsy for histology and culture is particularly important for those patients who
      fail to respond to the aforementioned treatment.

PMID- 8551158
TI  - Medullary carcinoma of the thyroid metastatic to the temporal bone.
AB  - We report a case of proven thyroid medullary carcinoma, metastatic to the
      temporal bone. Review of the otolaryngology literature demonstrates that this is
      the first such report. The patient presented with symptoms, physical examination,
      and imaging studies suggestive of a glomus jugulare tumour. The pre-operative
      diagnosis of metastatic thyroid medullary carcinoma, however, was made, based on
      a history of medullary carcinoma of the thyroid with previous metastases as well
      as an elevation in calcitonin levels. Histological examination of the surgical
      specimen confirmed the diagnosis.

PMID- 8551159
TI  - Occult thyroid carcinoma presenting as a parapharyngeal mass.
AB  - This report describes a 47-year-old male who had an occult papillary carcinoma of
      the thyroid present as a nodal involvement of the parapharyngeal space, in the
      retrostyloid compartment. To the best of our knowledge, this is an extremely rare
      condition.

PMID- 8551160
TI  - Synovial sarcoma of the pharynx.
AB  - Synovial sarcoma is rarely seen in the head and neck region. A case of synovial
      sarcoma of the pharynx in a child is presented.

PMID- 8551161
TI  - A tumour derived from Ebner's glands: microcystic adnexal carcinoma of the
      tongue.
AB  - Microcystic adnexal carcinoma (MAC) is known as an infiltrating but non
      metastasizing tumour of the skin, that derives from sweat glands or follicular
      epithelium. We report on a rare case of MAC of the tongue. The patient had
      noticed the tumour for two years with slowly increasing dysphagia but no other
      symptoms of an oropharynx carcinoma. Histological and immunohistochemical
      analyses showed a similarity between the tumour derived from Ebner's glands of
      the tongue and MAC of the sweat glands.

PMID- 8551162
TI  - Pharyngo-oesophageal fistula following iatrogenic perforation of a pharyngeal
      pouch.
AB  - A unique, previously undescribed case of iatrogenic perforation of a pharyngeal
      pouch which resulted in pharyngo-oesophageal fistulation is described. The
      correct management of such complications is discussed.

PMID- 8551163
TI  - The clunking neck.
AB  - A patient complaining of pain and noise on turning her neck was diagnosed as
      having a large greater cornua of the hyoid bone. Excision of the greater cornua
      relieved the symptoms.

PMID- 8551165
TI  - Orbital and skin metastases in a polymorphous low grade adenocarcinoma of the
      salivary gland.
AB  - We report the previously undocumented development of an orbital metastasis and
      skin metastases in a patient with polymorphous low grade adenocarcinoma (PLGA) 15
      years after initial presentation. The clinical course, treatment and changing
      histological features are discussed.

PMID- 8551164
TI  - Removal of superglue from the external ear using acetone: case report and
      literature review.
AB  - The ability of superglue preparations (cyanoacrylate) to bond instantly to skin
      as well as inanimate objects presents a special problem when instilled into the
      external ear canal. We present two cases of patients who had it successfully
      removed under the microscope with the help of acetone BP to debond it from the
      skin, without any damage to the meatus or the tympanic membrane. The third
      patient had the superglue removed without the help of acetone but sustained
      damage to the tympanic membrane. A literature review of similar cases is
      included.

PMID- 8551166
TI  - Multiple oncocytic cysts of the larynx.
AB  - Oncocytic metaplasia in laryngeal epithelium is uncommon. Oncocytes have been
      described in the lining of laryngeal cysts and such cysts have been reported in
      the literature under a variety of names. There is an ongoing debate about the
      exact nature of 'oncocytic cysts', which tend to be solitary. An unusual case of
      multiple oncocytic cysts of the larynx is described. The pathology and treatment
      are discussed.

PMID- 8551167
TI  - The reliability of acoustic rhinometry.

PMID- 8551168
TI  - KTP/532 laser tonsillectomy--a potential day-case procedure.

PMID- 8551170
TI  - Ischemia monitoring with on-line vectorcardiography compared with results from a
      predischarge exercise test in patients with acute ischemic heart disease.
AB  - Information from 24-hour monitoring with on-line vectorcardiography, starting
      immediately after admission, was compared with results from a predischarge
      exercise test 3-13 days after admission. A total of 169 patients with acute
      myocardial infarction and 73 patients with unstable angina pectoris were
      investigated. Patients were followed for 487 +/- 135 days. During the follow-up
      period, 19 patients (8%) died from cardiac causes and 34 (14%) were hospitalized
      for a myocardial infarction. The QRS vector difference (QRS-VD), ST change vector
      magnitude (STC-VM), ST vector magnitude (ST-VM), and ST vector leads X, Y, Z were
      monitored. Patients with ST depression on the exercise test showed higher
      occurrence of transient, supposedly ischemic, episodes of QRS-VD, STC-VM, and ST
      VM than patients without ST depression. The sensitivity and specificity of
      identifying patients with ST depression at the exercise test were respectively,
      71 and 47% for QRS-VD episodes, 58 and 56% for ST-VM episodes, and 55 and 65% for
      STC-VM episodes. The maximum ST depression at the exercise test was related to
      the maximum ST depression in vector lead X (r = .44, P < .001) and the number of
      STC-VM (r = .40, P < .001), ST-VM (r = .37, P < .001), and QRS-VD (r = .33, P <
      .001) episodes on the VCG. In multivariate analysis, maximum ST depression in
      vector lead X and STC-VM episodes were the best determinants for ST depression at
      the exercise test. In a Cox regression model, the optimal combination of exercise
      test data in patients who died from cardiac causes exhibited a global chi-square
      value of 20.0. The combination of these data and the number of STC-VM episodes
      increased the global chi-square value to 30.6. This study indicates that in
      patients with acute ischemic heart disease, early continuous vectorcardiographic
      monitoring may predict the results from a predischarge exercise test and also
      contributes independent prognostic information beyond that of exercise test data.

PMID- 8551169
TI  - Unexplained gradual-onset Q wave patterns. A case series from the Framingham
      Study.
AB  - Original cohort members of the Framingham Study were studied to determine
      prognosis associated with unexplained (gradual-onset) Q wave patterns detected on
      routine electrocardiograms (ECGs). Biennial ECGs were obtained on subjects
      beginning in 1948. The index ECG was read independently and then serially in
      relation to all previous tracings for evidence of myocardial infarction.
      Proportional hazards modeling was used to assess the risk for outcomes in those
      with unexplained (gradual-onset) Q wave patterns compared with subjects with
      unrecognized myocardial infarcts (abrupt-onset Q waves) and compared with
      referent subjects. Unexplained Q wave patterns developed in 53 men and 39 women.
      Subjects with unexplained Q wave patterns had less than 40% of the risk for
      myocardial infarction or coronary death as compared with those with unrecognized
      myocardial infarction after adjusting for risk factors (hazard ratio, 0.38; 95%
      confidence interval, 0.19, 0.78; P = .008) and a trend toward a lower risk for
      overall mortality (adjusted hazard ratio, 0.73; 95% confidence interval, 0.46,
      1.16; P = .18). Risks for myocardial infarction or coronary death and overall
      mortality were similar in subjects with unexplained Q wave patterns and referent
      subjects in the fully adjusted models. Detection of prominent Q waves on an ECG
      requires comparison with prior tracings to differentiate the unexplained Q wave
      pattern from the unrecognized infarct, conditions that have significantly
      different prognostic implications.

PMID- 8551171
TI  - Comparison of digitized ECGs simultaneously recorded with CR and V leads.
AB  - Evidence is presented that electrocardiograms recorded with bipolar chest-right
      arm (CR) leads are diagnostically similar to electrocardiograms recorded with
      unipolar V leads. Electrocardiograms were simultaneously recorded with CR and V
      leads on six chest sites in 45 cardiac patients and submitted, unmarked, for
      evaluation, by four cardiologists. In spite of relatively small differences in
      the amplitudes of P, Q, R, S, and T waveforms, the diagnosis based on tracings
      recorded with CR leads was similar to the diagnosis based on tracings recorded
      with V leads in nearly 90% of patients. Because CR leads are set up with only two
      electrodes, one on the right arm and one on the chest, their use in cardiac
      emergencies saves time and simplifies the recording technique. This investigation
      is part of a project aimed at developing a portable electrocardiograph for use
      outside the hospital or clinic.

PMID- 8551172
TI  - Premature atrial beat eliciting atrial fibrillation after coronary artery bypass
      grafting.
AB  - Of patients undergoing coronary artery bypass grafting 30% develop atrial
      fibrillation (AF) or flutter. To determine if AF is initiated from the right or
      left atrium, atrial electrograms were continuously recorded in patients
      undergoing this procedure. In addition, to study whether the prematurity index of
      premature atrial contractions (PACs) eliciting AF differs from PACs not provoking
      AF, the distribution of prematurity indices was evaluated from R-R interval
      analysis. The right and left atrial recording electrodes were first activated by
      the ectopic beat provoking AF in six and eight patients, respectively. The
      prematurity index of the PAC eliciting AF was located in the middle (in half of
      the patients) or to the left of the median distribution of prematurity indices.
      The variability in activation of the atrial electrodes suggests that the PAC
      provoking AF can have its origin in the right, the septal, or the left region of
      the atrium. The initiation of AF depends on the prematurity index of the PAC.

PMID- 8551173
TI  - Ethanol intake, plasma catecholamine levels, and ST-segment changes without
      myocardial injury in rats with short-term ethanol consumption.
AB  - The authors studied the effect of short-term ethanol consumption on the ST
      segment and the association between ST-segment changes and the amount of daily
      ethanol intake and levels of plasma catecholamines. The study used 63 rats
      (control group n = 20, study group n = 43). The rats in the study group were
      exposed for 6 days to progressively larger doses of ethanol followed by 15 days
      of continuous exposure to ethanol. At baseline an electrocardiogram (ECG) was
      recorded, and on day 25 the ECG was repeated and plasma catecholamine levels were
      measured. The animals' hearts were removed and processed for histologic study.
      Repolarization abnormalities were observed in 68% of the ethanol-consuming rats.
      Two factors differentiated the subgroup of ethanol-consuming rats with ST-segment
      changes from the subgroup without ST-segment changes: amount of daily ethanol
      intake (0.0077 +/- 0.02 mL/g/d vs 0.0058 +/- 0.019 mL/g/d) and plasma epinephrine
      levels (3,881 +/- 733 pg/mL vs 1,478 +/- 406 pg/mL). No myocardial damage was
      detected. Our results suggest that in ethanol-consuming rats, high-volume daily
      ethanol intake and increased plasma catecholamines may mediate changes in the ST
      segment.

PMID- 8551174
TI  - Exaggerated atrial repolarization waves as a predictor of false positive exercise
      tests in an unselected population.
AB  - The authors previously postulated that a markedly downsloping PR-segment might be
      a marker for exaggerated atrial repolarization waves and demonstrated PR-segment
      appearance to be an independent predictor of a false positive exercise test. This
      study was conducted to determine the sensitivity, specificity, and predictive
      value of markedly downsloping PR-segments for predicting false positive exercise
      tests. The study group consisted of 82 consecutive patients with a positive
      exercise test (> or = 1.0 mm horizontal ST depression) and a normal resting
      electrocardiogram. Tests were predicted to be false positive based on previously
      defined criteria: (1) markedly downsloping PR-segments in two or more of leads
      II, III, and aVF and (2) exercise duration 4 minutes or longer. Patients were
      then classified according to available clinical information (coronary angiography
      and radionuclide stress testing) into true positive (due to myocardial ischemia,
      n = 62) and false positive (n = 20) groups. The sensitivity, specificity, and
      predictive value of the PR-segment/exercise duration criterion for predicting a
      false positive test were 70, 74, and 47%, respectively. Patients with false
      positive tests also had higher heart rates (158 +/- 16 vs 136 +/- 20 beats/min, P
      < .001) and less frequent chest pain (15 vs 46%, P = .017) during the exercise
      test. Patients with false positive exercise tests can be recognized by the
      achievement of a high peak exercise heart rate, the absence of exercise-induced
      chest pain, and the appearance of markedly downsloping PR-segments in the
      inferior leads.

PMID- 8551175
TI  - Transient disappearance of complete right bundle branch block during exercise in
      a patient with old inferior wall myocardial infarction.
AB  - To date, there has been no report of temporary disappearance of right bundle
      branch block (RBBB) during exercise. A patient with old infero-posterior
      myocardial infarction is described in whom complete RBBB disappeared transiently
      during treadmill exercise testing. No chest pain or significant ST-T changes
      occurred during and after the exercise periods. Any of the following mechanisms
      could have been involved: (1) the patient's complete RBBB might have been
      bradycardia-dependent, (2) an exercise-induced increase of sympathetic tone might
      have produced a temporary improvement of the conduction disturbances, or (3) the
      exercise might have elicited conduction disturbances in the main left bundle
      branch, which could have concealed a conduction delay in the main trunk of the
      right bundle branch.

PMID- 8551176
TI  - Septic cardiomyopathy as a cause of long QT syndrome.
AB  - A 63-year-old woman admitted with 2:1 infranodal atrioventricular block
      subsequently developed ventricular dysfunction incident to septic syndrome.
      Concomitant changes included an abnormally prolonged QTc interval (600 ms) and
      the occurrence of torsade de pointes. Restoration of a normal QTc interval and
      cessation of torsade de pointes was coincident with return of normal ventricular
      function and remission of sepsis. This report supports the view that sepsis
      induced cardiomyopathy is another cause of the long QT syndrome.

PMID- 8551177
TI  - Electropharmacological actions of propofol on calcium current in guinea-pig
      ventricular myocytes.
AB  - Propofol, a widely-used intravenous anesthetic, causes bradycardia, depression in
      contractility and hypotension. The cellular mechanisms responsible for these
      cardiac toxicity remain unclear. In this study, we examined the cellular
      electropharmacological actions of propofol on calcium current in guinea-pig
      heart. Single ventricular myocytes were freshly isolated from guinea-pig using
      modified enzymatic method. Whole-cell voltage-clamp technique was applied with
      one suction pipette. Transmembrane L-type calcium current (ICa(L)) was separated
      from other ionic currents by voltage-control, ionic channel blockers and ion
      substitution methods. Our results show that propofol decreased ICa(L) in a
      concentration-dependent manner (KD = 54.2 microM). Slope conductance of current
      voltage relation was decreased by 56 microM propofol. Propofol did not affect the
      steady-state activation curve, but shifted the inactivation curve to
      hyperpolarizing direction. Recovery from inactivation was slowed down by
      propofol. Marked resting block and use-dependent block were noted. In conclusion,
      our results indicate that propofol inhibits cardiac L-type calcium current mainly
      by shifting inactivation curve and retarding the recovery from inactivation.

PMID- 8551178
TI  - Selected short papers from the XXIInd International Congress on
      Electrocardiology. Building Bridges in Electrocardiology. Nijmegen, The
      Netherlands, June 25-29, 1995.

PMID- 8551179
TI  - Clinical applications of BSM.
AB  - Body surface mapping (BSM) has now become a feasible clinical technique,
      providing useful information applicable to the diagnosis of cardiac arrhythmias
      and their treatment by surgical and endocardial catheter ablation. In WPW
      patients, validation of preexcitation patterns has been obtained by computer
      simulation and by direct epicardial mapping at surgery. BSM pacemapping has
      subsequently been developed to be used during radiofrequency catheter ablation.
      This method has been evaluated prospectively and its predictive accuracy
      assessed. The recognition of two distinct BSM patterns in idiopathic ventricular
      tachycardia, has led to the application of successful pacemapping for
      radiofrequency catheter ablation. The use of a realistic tri-dimensional heart
      torso computer model has shown that specific sites of endocardial stimulation are
      related to distinct thoracic map patterns.

PMID- 8551180
TI  - On the potential of the Wilson central terminal with respect to an ideal
      reference for unipolar electrocardiography.
AB  - Body surface potential mapping was performed in 60 clinical cases and an ideal 0
      potential was calculated in each case at 2msec intervals, which corresponds to
      the potential at infinity. Maximal deviation of the Wilson terminal voltage the
      ideal potential was 0.14mv on the average. Time course of potential variations of
      the central terminal was in proportion to the measured surface potentials. The
      lead vector of Wilson terminal was determined for each case, with a method to
      make a minimal difference between calculate and observed Wilson terminal voltage.
      The lead vector was directed superiorly and posteriorly with the magnitude of 24%
      of that of lead I on the average.

PMID- 8551181
TI  - Differences in the effect of acute ischemia on late potentials in susceptible and
      resistant dogs for sudden cardiac death.
AB  - The low predictive value of the signal averaged ECG (SAECG) at rest may be due to
      the absence of any physiological perturbation. This study assessed changes of
      late potentials (LP) in the SAECG due to acute ischemia in five susceptible (S)
      and five resistant (R) dogs for sudden cardiac death. SAECGs were measured at
      rest prior to and during the last 3 min of 4 min transient occlusion of the left
      circumflex artery (CAO). At rest no significant differences were seen in the QRS
      duration (QRSD), the low amplitude signal duration (LAS40) and the root mean
      square voltage (RMS20) between S and R dogs. However, acute ischemia caused
      significant increases in QRSD and LAS40, but only in the S dogs. These results
      indicate differences in the ischemic modulation of the arrhythmogenic substrate
      in S and R group. Analysis of LP during acute ischemia may provide an important
      increase in the positive predictive value of the SAECG.

PMID- 8551182
TI  - Single beat late potentials extracted from the matrix of surface
      electrocardiograms.

PMID- 8551183
TI  - A theorem concerning myocardial activation imaging.
AB  - We present a theorem which is the basis of a new approach to imaging ventricular
      surface activation. Application of the theorem in realistic simulations and with
      human data is presented elsewhere in this conference.

PMID- 8551184
TI  - Lead system transformation for pooling of body surface map data: a surface
      Laplacian approach.
AB  - In this paper, a method is described to transform Body Surface Map (BSM) data
      from one lead system to that of another. This enables pooling of BSM data between
      different centres. The transformation tool is based upon Laplacian interpolation.
      It is evaluated by inspecting transformations from lead systems having few leads
      to one having many leads.

PMID- 8551185
TI  - Comparison of body surface potential maps simulated with isotropic and
      anisotropic computer heart models.
AB  - Simulated body surface potential maps (SBSPM) with isotropic and anisotropic
      heart models were compared to investigate the effect of myocardial anisotropy on
      body surface electrocardiograms at a whole heart level. Rotative fiber
      orientations of total 90 degrees was incorporated into an isotropic heart model.
      The anisotropy of conduction velocity and intracellular electric conductivity was
      included in the simulation. SBSPM based on epicardial, intramural, and
      endocardial stimulation show high correlation with fiber orientations. On the
      other hand, the anisotropy cannot be distinguished from the SBSPM in the
      simulation of normal heart model.

PMID- 8551186
TI  - Frank electrocardiograms.
AB  - Frank electrocardiograms were recorded in 426 schoolchildren (225 girls, 201
      boys) aged 10 to 14 years, planar vectorcardiograms projected onto the horizontal
      and left sagittal planes were constructed. Spatial magnitude of instantaneous QRS
      vector end-points in 10 ms intervals of QRS duration, and of maximum QRS vector,
      as well as X, Y, Z coordinates of instantaneous QRS vector end-points in 10 ms
      intervals of QRS duration, and of the maximum QRS vector were analyzed in
      relation to weight, height and BMI. The initial part of VCG loop was not
      influenced by age and anthropometric parameters, respectively. The spatial QRS
      vector magnitude at the 30 ms of QRS decreased significantly with age and height.
      From the 40 ms of QRS duration the VCG parameters were significantly related to
      anthropometric parameters. Vectorcardiographic parameters were more influenced by
      the anthropometric parameters then by age.

PMID- 8551187
TI  - A method to reduce the effect of electrode position variations on automated ECG
      interpretation.
AB  - To reduce the effect of electrode position variations on the diagnostic
      interpretation of an ECG, ECG and VCG interpretations were combined. The
      reduction was assessed by generating ECGs with displaced electrodes for a group
      of subjects using Body Surface Potential Maps (BSPMs). VCGs were reconstructed
      from the ECGs. The group consisted of normals, cases with myocardial infarction
      (MI), and with left ventricular hypertrophy (LVH). The effects of four types of
      electrode position changes were assessed for the diagnostic categories MI and
      LVH. The combined interpretation proved to be less sensitive to large changes
      than either the ECG or the VCG interpretation alone. The number of small changes
      increased for the combined interpretation. The combined interpretation showed
      higher agreement with a human expert than the ECG interpretation alone.

PMID- 8551188
TI  - Electrophysiological properties of two distinct populations of myocytes isolated
      from the rabbit atrioventricular node.

PMID- 8551189
TI  - Electric instability after myocardial infarction displayed in body surface
      potential maps.
AB  - A longitudinal study during the first year after myocardial infarction (MI) was
      performed in 12 patients (pts) to evaluate the reversibility of the electric
      heart field changes occurring during the acute phase by means of body surface
      potential mapping (BSPM). Using correlation coefficients we showed that the
      inversion of electric processes in myocardial depolarization and/or
      repolarization during acute phase of MI displays irreversible damage of the
      myocardium that means high risk for the pt and that the healing of infarcted
      heart is not completed within 6 months after MI at least from the electrical
      point of view.

PMID- 8551190
TI  - Development of linear and non-linear properties of heart rate control during
      quiet and active sleep in healthy infants.
AB  - In this study it is analyzed by linear and non-linear methods, how the control of
      instantaneous heart rate (IHR) develops in infants in quiet and active sleep. Ten
      healthy and term newborns were studied during their first half year of life. Low
      (LF) and high frequency power (HF) of the spectrum, and the largest Lyapunov
      exponent (LLE) were calculated from IHR. By means of the surrogate-data-test,
      significance of LLE with respect to linear correlated gaussian noise was
      verified. Significant differences were determined between the original and the
      surrogate data sets (p < 0.001) assuming non-linear properties. LF, HF, LLE have
      irregular developmental patterns during the first month, whereby LLE has a
      distinct low value on the 21st day. HF significantly increases between the second
      and sixth month in quiet sleep, whereas for LF and LLE no significant
      correlations were found, neither for quiet nor active sleep. Using linear and non
      linear methods, the study shows that the system controlling heart rate pass
      through mainly two different developmental periods: a period of adaptation in the
      first four weeks, where parameters distinctly vary, followed by a period with
      clear developmental courses, lasting till the sixth month.

PMID- 8551191
TI  - Pigeons' preference for variable-interval water reinforcement under widely varied
      water budgets.
AB  - Water budget of pigeons was varied to assess the dependence of risk-sensitive
      preferences upon economic context such as has been reported for energy-budget
      manipulations with small animals in behavioral ecology research. Fixed- and
      variable-interval terminal-link water schedules reinforced choice between equal
      variable-interval initial-link schedules arranged on two pecking keys. While
      keeping a severely restrictive budget the same across three phases of the
      experiment, a contrasting distinct ample budget was arranged in each. To mimic
      typical methods in behavioral ecology studies, in each ample budget a more than
      three-fold increase in amount of water per reinforcer presentation was instituted
      simultaneously with significantly increased overall access to water. Total choice
      response rates plummeted in the ample budgets, and body weights either increased
      significantly or remained unchanged in different phases as expected by the nature
      of the different manipulations. Clear preferences for the variable-interval
      schedule were found throughout the experiment, except for rare instances of key
      bias. The results agree with similar operant food-reinforcement studies and
      extend conditions under which risk preference apparently does not depend upon
      economic context.

PMID- 8551192
TI  - Behavioral economics of concurrent ethanol-sucrose and sucrose reinforcement in
      the rat: effects of altering variable-ratio requirements.
AB  - These experiments examined the own-price and cross-price elasticities of a drug
      (ethanol mixed with 10% sucrose) and a nondrug (10% sucrose) reinforcer. Rats
      were presented with ethanol-sucrose and sucrose, both available on concurrent
      independent variable-ratio (VR) 8 schedules of reinforcement. In Experiment 1,
      the variable ratio for the ethanol mix was systematically raised to 10, 12, 14,
      16, 20, and 30, while the variable ratio for sucrose remained at 8. Five of the 6
      rats increased ethanol-reinforced responding at some of the increments and
      defended baseline levels of ethanol intake. However, the rats eventually ceased
      ethanol-reinforced responding at the highest variable ratios. Sucrose-reinforced
      responding was not systematically affected by the changes in variable ratio for
      ethanol mix. In Experiment 2, the variable ratio for sucrose was systematically
      increased while the ethanol-sucrose response requirement remained constant. The
      rats decreased sucrose-reinforced responding and increased ethanol-sucrose
      reinforced responding, resulting in a two- to 10-fold increase in ethanol intake.
      Experiment 3 examined the substitutability of qualitatively identical
      reinforcers: 10% sucrose versus 10% sucrose. Increases in variable-ratio
      requirements at the preferred lever resulted in a switch in lever preference.
      Experiment 4 examined whether 10% ethanol mix substituted for 5% ethanol mix,
      with increasing variable-ratio requirements of the 5% ethanol. All rats
      eventually responded predominantly for the 10% ethanol mix, but total amount of
      ethanol consumed per session did not systematically change. In Experiment 5, the
      variable-ratio requirements for both ethanol and sucrose were simultaneously
      raised to VR 120; 7 of 8 rats increased ethanol-reinforced responding while
      decreasing sucrose-reinforced responding. These data suggest that, within this
      ethanol-induction procedure and within certain parameters, demand for ethanol
      sucrose was relatively inelastic, and sucrose consumption was independent of
      ethanol-sucrose consumption. Demand for sucrose, on the other hand, was
      relatively elastic, and ethanol-sucrose readily substituted for it. The results
      are discussed in terms of applying a behavioral economic approach to
      relationships between drug and nondrug reinforcers.

PMID- 8551193
TI  - Unit-price analysis of opioid consumption by monkeys responding under a
      progressive-ratio schedule of drug injection.
AB  - Several reports have indicated that drug consumption in self-administration
      procedures is a function of the ratio of the instrumental requirement to the dose
      of drug, a quantity termed unit price. We evaluated three predictions from this
      unit-price model in a reanalysis of data on opioid self-administration in rhesus
      monkeys responding under a progressive-ratio schedule (Hoffmeister, 1979). We
      evaluated whether consumption was inversely related to unit price, and compared
      the goodness of fit of an equation devised by Hursh, Raslear, Shurtleff, Bauman,
      and Simmons (1988) to that of a linear model predicting consumption as a function
      of dose. We also tested whether consumption was constant when the same unit price
      was comprised of different combinations of dose and instrumental requirement.
      Consumption declined overall as unit price increased. The equation devised by
      Hursh et al. and the linear model based on dose fit the data equally well. Drug
      consumption was not uniform at a given unit price. The analyses suggest limits on
      the unit-price model as a characterization of drug consumption.

PMID- 8551194
TI  - Normalized demand for drugs and other reinforcers.
AB  - The concepts of behavioral economics have proven to be useful for understanding
      the environmental control of overall levels of responding for a variety of
      commodities, including reinforcement by drug self-administration. These general
      concepts have implications for the assessment of abuse liability and drug abuse
      intervention and the formulation of public policy on drug abuse. An essential
      requirement is the ability to compare the demand for different drugs directly in
      order to assess relative abuse liability, and to compare demand for the same drug
      under different environmental and biological interventions to assess their
      ability to reduce demand. Until now, such comparisons were hampered by the
      confounding effect of varying drug doses and potencies that prevent quantitative
      comparisons of demand elasticity--sensitivity of consumption and responding to
      the constraint of price (effort). In this paper we describe a procedure to
      normalize demand-curve analysis that permits dose- and potency-independent
      comparisons of demand across drugs. The procedure is shown to be effective for
      comparing drug demand within and across the drug classes. The technique permits a
      quantitative ordering of demand that is consistent with the peak levels of
      responding maintained by the drugs. The same technique is generalized for the
      comparison of other types of reinforcers under different biological conditions.

PMID- 8551195
TI  - Behavioral economics without anomalies.
AB  - Behavioral economics is often conceived as the study of anomalies superimposed on
      a rational system. As research has progressed, anomalies have multiplied until
      little is left of rationality. Another conception of behavioral economics is
      based on the axiom that value is always maximized. It incorporates so-called
      anomalies either as conflicts between temporal patterns of behavior and the
      individual acts comprising those patterns or as outcomes of nonexponential time
      discounting. This second conception of behavioral economics is both empirically
      based and internally consistent.

PMID- 8551196
TI  - Platelet activation mechanisms and markers in arterial thrombosis.

PMID- 8551197
TI  - Atrial fibrillation--new aspects on mechanism and treatment.
AB  - During recent years, the exploration of different aspects of atrial fibrillation
      (AF) has become increasingly interesting. Thus, knowledge about basic underlying
      mechanisms, consequences and different modes of treatment has rapidly expanded.
      At a meeting in Lund, Sweden, in 1993, scientists within different fields of AF
      research gathered for the exchange of information. This paper is a short summary
      of some topics discussed at the Lund meeting and some suggestions as to how
      further research in this field may help to improve our understanding of this
      arrhythmia and the treatment of patients suffering from it. Underlying
      pathoelectrophysiological mechanisms in AF have been explored in experimental
      models in animals and by direct recordings of different atrial myocardial
      electrophysiological variables both in the catheter laboratory and during open
      heart surgery in man. Some findings illustrate possible generalized atrial
      myocardial mechanisms, whilst other findings clearly indicate the possibility of
      localized pathoelectrophysiological mechanisms. The generally accepted hypothesis
      that AF is perpetuated by multiple re-entry mechanisms is, thus, both verified
      and modified by recent studies. In addition to subjective symptoms and well
      identified thromboembolic consequences, accumulating evidence tells us that AF
      may precipitate a myocardial dysfunction which may be misinterpreted as an
      underlying factor initiating the arrhythmia. Today's treatment of AF includes
      several newer antiarrhythmic drugs, different ablation techniques, the
      application of different electrical devices as well as different surgical
      methods. New, improved and simplified methods are expected. Atrial fibrillation
      is the single most important supraventricular arrhythmia needing substantial
      further exploration of mechanisms, consequences and treatment. The Lund symposium
      contributed to this process by defining the state of knowledge in 1993 and
      outlining the need for the years to come.

PMID- 8551198
TI  - Continuous vectorcardiographic changes in relation to scintigraphic signs of
      reperfusion in patients with acute myocardial infarction receiving thrombolytic
      therapy.
AB  - OBJECTIVES: Changes in the electrical activity of the heart reflecting the
      infarct process can be recorded by continuous vector-ECG, a method which is now
      clinically available for cardiac supervision. Shifts of the ST-segment and QRS
      vector reflect ischaemia and necrosis of the myocardium. Continuous vector-ECG
      changes were evaluated against myocardial scintigraphy in 18 patients with acute
      myocardial infarction treated with streptokinase in order to study the impact of
      improved myocardial perfusion. DESIGN: Myocardial perfusion was analysed with
      99Tcm-Sestamibi (Cardiolite, DuPont Scandinavia AB, Kista, Sweden) single photon
      emission computerized tomography (SPECT). Registrations were performed before and
      after thrombolysis in order to estimate the amount of myocardium with impaired
      perfusion initially (threatened myocardium) and the degree of perfusion
      improvement in this myocardial area. X, Y, Z vectors were registered continuously
      by Frank leads (Ortivus Medical, Taby, Sweden). QRS-vector difference, and the
      time to plateau phase and the ST-vector magnitude were used as a measurement of
      ischaemia and size of the myocardial infarction. RESULTS: In seven out of 11
      patients treated within 3 h of onset of symptoms, an improvement in myocardial
      perfusion in the initially hypoperfused areas was achieved in contrast to none of
      the seven patients treated > 3 h after onset of pain (P < 0.05). In the whole
      patient material, there was a negative correlation between the time to plateau
      level for the QRS-vector and the improvement in myocardial perfusion (r = -0.53,
      P < 0.05). Among patients treated within 3 h, there was a negative correlation
      between the plateau level for the QRS-vector magnitude compared to the
      improvement in myocardial perfusion (r = -0.61, P < 0.05) and a negative
      correlation between the plateau level and the myocardial perfusion level after
      therapy (r = -0.69, P < 0.05). In these patients, there were also negative
      correlations between the maximal ST-vector magnitude and the myocardial perfusion
      both before and after thrombolysis (r = -0.81, P < 0.05 and r = -61, P < 0.05,
      respectively). CONCLUSION: Patients with marked improvement in myocardial
      perfusion indicating successful thrombolysis reach their plateau levels of the
      QRS-change faster and have lower total QRS-vector differences than patients
      without successful thrombolysis as reflected by myocardial scintigraphy. Patients
      with a high ST-vector magnitude have low perfusion levels both before and after
      therapy indicating a pronounced ischaemic damage of the myocardium. Thus, VCG
      changes reflect impairment in myocardial perfusion during acute myocardial
      infarction.

PMID- 8551199
TI  - Screening for diabetic retinopathy in South Africa with 60 degrees retinal colour
      photography.
AB  - OBJECTIVES: Comparison of 60 degrees mydriatic retinal photography, in screening
      for diabetic retinopathy, with diabetes clinic doctors, formal ophthalmological
      assessment, and with one or two 45 degrees fields. DESIGN: Consecutive subjects
      screened by clinicians and photography, and selected eyes evaluated by an
      ophthalmologist. Randomized photographs assessed through one or two 45 degrees
      fields (by masking the slides), and at 60 degrees. SETTING: The first 663
      patients attending for routine clinic visits and screened for retinopathy. MAIN
      OUTCOME MEASURES: The relative diagnostic sensitivity of screening methods, the
      utility of screening one eye only, and the costs of photographic screening.
      RESULTS: Compared to an ophthalmologist's assessment, retinal photography had a
      sensitivity of 93% and a specificity of 89% for any retinopathy, and 100 and 75%,
      respectively, for severe retinopathy. Photography detected 28% more retinopathy
      (16% severe) than the clinicians. Compared to a 60 degrees field, one 45 degrees
      field missed 31%, and 2 x 45 degrees fields 11% of retinopathy. Of 57 patients
      with retinopathy meeting referral criteria, 31 pairs of eyes had substantially
      discordant scores. The cost of diagnosis in a patient requiring referral to
      ophthalmologist was about US $37.00. CONCLUSIONS: 60 degrees retinal photography
      compares well with an ophthalmologists screening, and is better than clinical and
      one to two 45 degrees field assessments. Both retinae should be screened. This
      method is cost-effective in our hands.

PMID- 8551200
TI  - Association between plasma renin activity and metabolic cardiovascular risk
      factors in essential hypertension.
AB  - OBJECTIVES: To study the relationships between plasma renin activity and
      metabolic cardiovascular risk factors in patients with essential hypertension.
      SUBJECTS AND DESIGN: Patients with uncomplicated essential hypertension (n = 36)
      with a diastolic blood pressure of 95-115 mmHg were studied. Assessment of plasma
      renin activity (PRA) related to urinary sodium excretion was used to define
      subgroups with high (n = 12), medium (n = 16) and low renin profiles (n = 8).
      MAIN OUTCOME MEASURES: Fasting plasma lipid levels were determined. Glucose,
      insulin and C-peptide responses to standard oral glucose tolerance test (OGTT)
      were measured. RESULTS: Patients with high PRA had higher levels of plasma
      cholesterol (6.13 +/- 0.81 versus 4.67 +/- 0.7 mmol L-1, P < 0.05) and
      triglycerides (2.14 +/- 0.18 versus 0.98 +/- 0.13 mmol L-1, P < 0.05), than the
      low PRA group. HDL-cholesterol levels were lower in the high renin group than in
      the low renin group (1.05 +/- 0.04 versus 1.26 +/- 0.09 mmol L-1, P < 0.05).
      Insulin and C-peptide sums were higher in high PRA group (33.8 +/- 1.2 versus
      25.1 +/- 0.9 and 2.6 +/- 0.3 versus 1.9 +/- 0.4 ng L-1, P < 0.05), than in the
      low PRA group. CONCLUSIONS: Essential hypertensive patients with a high renin
      profile display more pronounced dyslipidaemia and higher levels of plasma insulin
      than patients with a low renin profile. This may be one explanation for higher
      incidence of cardiovascular disease previously reported in high PRA group.

PMID- 8551201
TI  - Increased incidence of thyrotoxicosis in Malmo during the years 1988-1990 as
      compared to the years 1970-1974.
AB  - OBJECTIVE AND DESIGN: To compare the total and age-specific incidence of
      thyrotoxicosis, as well as the incidence of the individual types of
      thyrotoxicosis [i.e. thyrotoxicosis of Graves' type (GD), toxic nodular goitre
      (TNG) and solitary toxic adenoma (STA)] in Malmo during the years 1988-1990 to
      those of a previous study in 1970-1974. SETTING: The town of Malmo in southern
      Sweden. SUBJECTS: All patients from the Malmo population treated for
      thyrotoxicosis (GD, TNG and STA) for the first time during the 3-year period 1988
      1990 were included. RESULTS: Overall, 299 (263 females and 36 males) new cases of
      thyrotoxicosis were diagnosed in 1988-1990, corresponding to a mean annual
      incidence of thyrotoxicosis of 43.0 per 100,000 inhabitants. The incidence of GD
      was 22.3, of TNG 16.0 and of STA 4.8 per 100,000 per year. Comparing age- and sex
      standardized incidences to the results in 1970-1974, there was a significant
      increase (P < 0.001) in the mean annual incidence of thyrotoxicosis in the total
      material as well as in TNG. In addition, there was an increase in GD in females
      younger than 50 years (P < 0.01), whereas in TNG/STA, an increase was seen in
      females of 50 years or older (P < 0.001). The incidence figures in males were not
      significantly changed. There was a higher proportion of smokers in females with
      GD compared to females with TNG (P < 0.001) and STA (P < 0.05). CONCLUSIONS: The
      total incidence of thyrotoxicosis, as well as the incidence of GD in females
      younger than 50 years and the incidence of TNG/STA in females of 50 years or
      older, has increased in Malmo during the period from 1970 to 1990. The increase
      was probably caused by several factors such as more sensitive diagnostic tools
      and GD changes in smoking habits, but additional unknown factors might also be of
      importance.

PMID- 8551202
TI  - Islet cell and glutamic acid decarboxylase antibodies in hyperthyroid patients:
      at diagnosis and following treatment.
AB  - OBJECTIVES: To study the frequency of islet cell (ICA) and glutamic acid
      decarboxylase (GAD-Ab) antibodies in patients with hyperthyroidism of different
      types at diagnosis before treatment and in the euthyroid state following
      treatment. SETTING: Department of Endocrinology, Malmo University Hospital,
      Malmo, Sweden. SUBJECTS AND DESIGN: Blood samples were collected at diagnosis
      from 129 hyperthyroid patients, and about 6 months later, from 78 of the patients
      (euthyroid state). Ninety-two patients had Graves' disease (69 females and 23
      males, median age 49 years, range 17-85 years), and 37 patients had toxic nodular
      goitre/solitary toxic adenoma (34 females and three males, median age 69 years,
      range 24-86 years). INTERVENTIONS: Most patients were treated by radioactive
      iodine following the first blood sample. MAIN OUTCOME MEASURES: ICA and GAD-Ab in
      serum. RESULTS: At diagnosis of Graves' disease, ICA were detected in two out of
      92 (2.2%) patients, two out of 85 (2.4%) without diabetes mellitus and in the
      euthyroid state in one patient. None of the patients with toxic nodular
      goitre/solitary toxic adenoma had detectable ICA. At diagnosis of Graves'
      disease, GAD65-Ab as well as GAD67-Ab were detected in 11 out of 85 (13%)
      patients without diabetes. As many as six out of 11 GAD67-Ab-positive patients
      were GAD65-Ab negative. In the euthyroid state, GAD65-Ab were found in six out of
      51 (12%) and GAD67-Ab in eight out of 51 (16%) of the non-diabetic Graves'
      disease patients. The frequencies of GAD65-Ab and GAD67-Ab in toxic nodular
      goitre/solitary toxic adenoma, diabetes excluded, were 3 and 0%, respectively, in
      the hyperthyroid state. CONCLUSION: The frequency of ICA in patients with
      hyperthyroidism is not increased as compared to the background population. GAD-Ab
      seems to be associated with Graves' disease and not with hyperthyroidism. The
      presence of GAD67-Ab in GAD65-Ab negative sera from patients with Graves' disease
      indicates autoreactivity against a specific GAD67 epitope.

PMID- 8551203
TI  - Predictors of enhanced well-being after coronary artery bypass surgery.
AB  - OBJECTIVES: To assess patients' perception of the therapeutic outcome after
      coronary artery bypass surgery, and to find predictors for increased well-being.
      DESIGN: Self-administered questionnaires (Family APGAR and GHQ-30) were completed
      on admission and at the follow-up after 12 months, together with functional
      classification according to the NYHA index. SETTING: Ulleval University Hospital,
      Oslo, Norway, 1990-1992. SUBJECTS: Two hundred and thirteen patients with stable
      angina admitted for elective coronary artery bypass surgery. INTERVENTION:
      Elective coronary artery bypass surgery. MAIN OUTCOME MEASURES: Improved physical
      and psychosocial functioning after one year. RESULTS: One hundred and ninety
      seven (92%) patients improved their NYHA class, while it remained stable or
      declined in 16 (8%) patients. Significantly fewer patients with mental distress
      were found at the follow-up than at the baseline examination (49 patients [23%]
      versus 80 patients [38%], respectively, P < 0.0001). One hundred and forty-six
      patients (69%) reported enhanced psychosocial well-being, while it was reduced (n
      = 60) or unchanged (n = 7) in 67 patients (31%). Predictors for improved
      psychosocial well-being following coronary artery bypass surgery were mental
      distress before surgery (odds ratio 2.8) and being a male patient (odds ratio
      2.8). CONCLUSIONS: The majority of the patients reported significant improvement
      in their physical and psychosocial functioning one year after coronary artery
      bypass surgery. Mental distress and male sex were significant predictors of
      enhanced well-being. Questionnaires on psychosocial well-being such as the GHQ-30
      may, in addition to health status measurements, offer additional useful
      information when coronary artery bypass surgery is considered.

PMID- 8551204
TI  - Lusoria dysphagia in a patient with retroperitoneal fibrosis and Riedel's
      thyroiditis.
AB  - The case history of a 68-year-old woman with progressive dysphagia caused by
      extrinsic compression of the oesophagus by an aberrant right subclavian artery or
      arteria lusoria is presented. Previous history mentioned a Riedel's thyroiditis,
      idiopathic retroperitoneal fibrosis and an aortic sclerosis. The authors want to
      report the case because it is an example of an association between lusoria
      dysphagia and retroperitoneal fibrosis, the connective tissue disease responsible
      for Riedel's thyroiditis, and perhaps, aortic sclerosis. This is the first report
      of this particular association.

PMID- 8551205
TI  - Aplastic anaemia with a trilineage response to erythropoietin therapy.
AB  - An 89-year-old man with a severe aplastic anaemia is described. The patient was
      proven to be cortico-steroid and cyclosporin resistant, but had a trilineage
      response during subsequent treatment with recombinant human erythropoietin.

PMID- 8551206
TI  - Psycho-neuro-immune-endocrine system: a three-phase-old response.

PMID- 8551207
TI  - Familial neurosarcoidosis.

PMID- 8551208
TI  - Iron deficiency in adolescent boys.

PMID- 8551209
TI  - Further exploration of human neonatal chromatic-achromatic discrimination.
AB  - Newborn (n = 140) and 1-month-old (n = 120) human infants were habituated to
      achromatic ("white") squares of varying luminance (.35 to 1.16 log cd/m2) and
      then tested for recovery of habituation with chromatic stimuli from particular
      spectral locations. Results showed that newborns appear to discriminate 32
      degrees yellow-green (dominant lambda = 565 nm) from white, but not 16 degrees or
      32 degrees blue (450 nm), 16 degrees blue-green (493 nm), 16 degrees or 32
      degrees yellow-green (572 nm), or 16 degrees purple from white. Performance of 1
      month-olds was marginally better than that of newborns. Combined with our
      previous results with the habituation method, these data imply that newborns show
      little ability to make any chromatic-achromatic discriminations when stimulus
      size is smaller than 8 degrees, and that even with very large stimuli (e.g. 32
      degrees) performance is relatively poor in the blue and yellow-green spectral
      regions. Although several models were considered, these limitations in the short-
      and mid-wavelength regions may best be accounted for by the argument that young
      infants possess general rather than selective immaturities or inefficiencies
      within their chromatic mechanisms.

PMID- 8551210
TI  - A production task evaluation of individual differences in mental addition skill
      development: internal and external validation of chronometric models.
AB  - A production task paradigm for obtaining reaction times to mental addition
      stimuli was used for internal and external validation of chronometric models of
      mental addition processing. The first analysis explored the internal validity of
      extant chronometric models and found that three models, (a) a tabular memory
      network retrieval strategy (PRODUCT), (b) a nontabular memory network retrieval
      strategy (ERROR RATE), and (c) a computational strategy (MIN), were able to
      encompass individual differences in strategy choice for 155 individuals from
      Grades 2 to 8 and 111 college students. Patterns of convergent and discriminant
      validity for these models were also demonstrated. The second analysis explored
      the external validity of relations among (a) two traditionally measured factor
      analytic dimensions of ability, Numerical Facility and Perceptual Speed; (b) two
      information processing dimensions presumed to underlie mental addition. Addition
      Efficiency and Speediness; and (c) a digit-span measure of Short-Term Memory. We
      specified a series of two-group (grade school and college) structural equation
      models to represent the relations among all measures and showed that individual
      differences in the apparently calculative processes that underlie the
      traditionally defined ability dimension of Numerical Facility are highly related
      to individual differences in Addition Efficiency and Speediness of information
      processing.

PMID- 8551211
TI  - The effects of task comprehension on preschoolers' and adults' categorization
      choices.
AB  - In experimental tasks in which subjects sort sets of objects with conflicting
      appearances and taxonomic relations, preschoolers often have been found to
      categorize according to appearance. The procedures used in past studies, however,
      may have biased preschoolers to attend to appearance instead of taxonomic
      relations. This possibility was examined in two experiments. In Experiment 1,
      children's preference for taxonomic- or appearance-based sorting was affected by
      both the training and the instructions they received. Adults in Experiment 1 were
      affected by instructions, but not by training. In Experiment 2 preschoolers
      sorted above chance according to the criterion for which they received training
      and instruction (taxonomic relations or appearance). Consistency data, children's
      justifications, and spontaneous labeling support the conclusions that training
      and instructions have a significant effect on children's preference to sort
      according to taxonomic relations or appearance, and that both criteria can be
      used systematically by children as young as four. Implications for task
      comprehension, flexibility, methodology, and education are discussed.

PMID- 8551212
TI  - Sorting out the cytokines of asthma.

PMID- 8551213
TI  - Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine
      model of acute airway hyperreactivity.
AB  - Reversible airway hyperreactivity underlies the pathophysiology of asthma, yet
      the precise mediators of the response remain unclear. Human studies have
      correlated aberrant activation of T helper (Th) 2-like effector systems in the
      airways with disease. A murine model of airway hyperreactivity in response to
      acetylcholine was established using mice immunized with ovalbumin and challenged
      with aerosolized antigen. No airway hyperractivity occurred in severe combined
      immunodeficient mice. Identically immunized BALB/c mice developed an influx of
      cells, with a predominance of eosinophils and CD4+ T cells, into the lungs and
      bronchoalveolar lavage fluid at the time that substantial changes in airway
      pressure and resistance were quantitated. Challenged animals developed marked
      increases in Th2 cytokine production, eosinophil influx, and serum immunoglobulin
      E levels. Neutralization of interleukin (IL) 4 using monoclonal antibodies
      administered during the period of systemic immunization abrogated airway
      hyperractivity but had little effect on the influx of eosinophils. Administration
      of anti-IL-4 only during the period of the aerosol challenge did not affect the
      subsequent response to acetylcholine. Finally, administration of anti-IL-5
      antibodies at levels that suppressed eosinophils to < 1% of recruited cells had
      no effect on the subsequent airway responses. BALB/c mice had significantly
      greater airway responses than C57BL/6 mice, consistent with enhanced IL-4
      responses to antigen in BALB/c mice. Taken together, these data implicate IL-4
      generated during the period of lymphocyte priming with antigen in establishing
      the cascade of responses required to generate airway hyperractivity to inhaled
      antigen. No role for IL-5 or eosinophils could be demonstrated.

PMID- 8551214
TI  - Evidence for a conformational change in a class II major histocompatibility
      complex molecule occurring in the same pH range where antigen binding is
      enhanced.
AB  - Many class II histocompatibility complex molecules bind antigenic peptides
      optimally at low pH, consistent with their exposure to antigen in acidic
      endosomal compartments. While it has been suggested that a partially unfolded
      state serves as an intermediate involved in peptide binding, very little evidence
      for such a state has been obtained. In this report, we show that the murine class
      II molecule IE becomes increasingly less stable to sodium dodecyl sulfate-induced
      dissociation since the pH is decreased in the same range that enhances antigenic
      peptide binding. Furthermore, at mildly acidic pH levels, IEk binds the
      fluorescent dye 1-anilino-naphthalene-8-sulfonic acid (ANS), a probe for exposed
      nonpolar sites in proteins, suggesting that protonation produces a molten globule
      like state. The association of IEk with a single high-affinity peptide had only a
      small effect in these two assays, indicating that the changes that occur are
      distal to the peptide-binding groove. Circular dichroism analysis shows that a pH
      shift from neutral to mildly acidic pH causes subtle changes in the environment
      of aromatic residues but does not grossly disrupt the secondary structure of IEk.
      We propose a model in which perturbations in interdomain contacts outside the
      peptide-binding domain of IEk occur at acidic pH, producing a partially unfolded
      state that facilitates optimal antigen binding.

PMID- 8551215
TI  - A structural transition in class II major histocompatibility complex proteins at
      mildly acidic pH.
AB  - Peptide binding by class II major histocompatibility complex proteins is
      generally enhanced at low pH in the range of hydrogen ion concentrations found in
      the endosomal compartments of antigen-presenting cells. We and others have
      proposed that class II molecules undergo a reversible conformational change at
      low pH that is associated with enhanced peptide loading. However, no one has
      previously provided direct evidence for a structural change in class II proteins
      in the mildly acidic pH conditions in which enhanced peptide binding is observed.
      In this study, susceptibility to denaturation induced by sodium dodecyl sulfate
      (SDS) detergent or heat was used to probe the conformation of class II at
      different hydrogen ion concentrations. Class II molecules became sensitive to
      denaturation at pH 5.5-6.5 depending on the allele and experimental conditions.
      The observed structural transition was fully reversible if acidic pH was
      neutralized before exposure to SDS or heat. Experiments with the environment
      sensitive fluorescent probe ANS (8-anilino-1-naphthalene-sulfonic acid) provided
      further evidence for a reversible structural transition at mildly acidic pH
      associated with an increase in exposed hydrophobicity in class II molecules. IAd
      conformation was found to change at a higher pH than IEd, IEk, or IAk, which
      correlates with the different pH optimal for peptide binding by these molecules.
      We conclude that pH regulates peptide binding by influencing the structure of
      class II molecules.

PMID- 8551216
TI  - Activation and negative selection of functionally distinct subsets of antibody
      secreting cells by influenza hemagglutinin as a viral and a neo-self antigen.
AB  - We have compared transgenic mice that express the influenza virus PR8
      hemagglutinin (PR8 HA) as a membrane-bound neo-self antigen (HA104 mice) with
      nontransgenic (non-Tg) mice for their ability to generate HA-specific B cell
      responses after primary immunization with PR8 virus. HA-specific, IgM-secreting B
      cells were induced with similar frequencies in HA104 and non-Tg mice. In
      addition, a B cell clonotype (C4) that is characteristic of anti-HA immune
      responses of BALB/c mice was identified among HA-specific IgM hybridomas from
      HA104 mice. A subset of HA-specific, IgG-secreting B cells that arises rapidly
      after primary virus immunization in non-Tg mice, however, was substantially
      reduced in HA104 mice. Likewise, a B cell clonotype (C12) that dominates HA
      specific IgG hybridomas generated after primary immunization of non-Tg mice was
      present at greatly reduced frequencies among hybridomas from HA104 mice. Because
      HA-specific, IgG-secreting B cells were generated by HA104 mice in response to a
      mutant HA containing an amino acid interchange in a B cell antigenic site, we
      conclude that these PR8 HA-specific, IgG-secreting B cells are negatively
      selected in HA104 mice as a result of their specificity for the neo-self PR8 HA.
      The findings demonstrate that HA-specific B cells that display distinct
      phenotypic potentials in non-Tg mice also differ in their susceptibility to
      negative selection from the primary B cell repertoire of HA104 mice: a subset of
      B cells that undergo rapid differentiation to become HA-specific IgG antibody
      secreting cells (ASC) after activation in non-Tg mice is negatively selected in
      HA104 mice. By contrast, a subset that gives rise to HA-specific, IgM-secreting
      ASC persists in the primary repertoire of HA104 mice and can be activated by
      virus immunization.

PMID- 8551217
TI  - Lipoxin A4 and B4 are potent stimuli for human monocyte migration and adhesion:
      selective inactivation by dehydrogenation and reduction.
AB  - Monocyte recruitment and adherence are important events in inflammatory and
      vascular diseases. Here, we evaluated the actions of lipoxin A4 (LXA4) and LXB4,
      a series of lipoxygenase products from arachidonic acid generated by cell-cell
      interactions, on human monocytes. LXA4 and LXB4 (10(-7) M) each increased
      monocyte migration in chamber chemotaxis assays and, in migration under agarose,
      exhibited chemotactic indices similar to those of the chemotactic peptide formyl
      methionyl-leucyl-phenylalanine at 10(-10)-10(-8) M and to the chemokine
      macrophage inflammatory protein-1 alpha (MIP-1 alpha) at 10(-8)-10(-7) M with a
      rank order of potency: Monocyte chemotactic protein-1 alpha > LXA4 approximately
      LXB4 approximately MIP-1 alpha. Lipoxins also stimulated monocyte adherence to
      laminin. In addition, human monocytes rapidly transformed LXA4 and LXB4 to
      several metabolites. LXB4 (> 80%) was converted within 30 s to new products, in a
      trend similar to that of LXA4. The novel monocyte-derived LXB4 products were
      identified as 5-oxo-6,7-dihydro-LXB4 and 6,7-dihydro-LXB4, indicating a role for
      site-selective dehydrogenation and reduction. Unlike monocytes, intact
      polymorphonuclear leukocytes (PMN) did not metabolize LXA4 in significant
      quantities, and only approximately 12% of exogenous LXB4 was omega-oxidized to 20
      OH-LXB4 and 20-COOH-LXB4 by PMN. To determine if lipoxin conversion altered
      bioactivity, we evaluated the actions of these metabolites on monocytes. Each of
      the novel products of LXA4 and LXB4 from monocytes, namely oxo- and
      dihydrolipoxins, were essentially inactive in stimulating monocyte adherence. In
      contrast, the omega-oxidation products of LXB4 isolated from PMN were equipotent
      with LXB4 for monocyte adherence. Dehydrogenation of LXA4 in monocytes appears to
      be carried out by a 15-hydroxyprostaglandin dehydrogenase, which is present in
      human monocytes as determined by reverse transcription PCR and Western blots.
      Together, these results provide the first evidence that LXA4 and LXB4 are both
      potent stimulants for migration and adherence of human monocytes. Moreover, they
      underscore the importance of the major route of lipoxin metabolism in leukocytes,
      namely, the rapid dehydrogenation and inactivation carried out by monocytes.

PMID- 8551218
TI  - The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic
      cells.
AB  - Interleukin (IL) 12 is a proinflammatory cytokine produced by phagocytic cells, B
      cells, and other antigen-presenting cells that modulates adaptive immune
      responses by favoring the generation of T helper type 1 cells. IL-12 mediates
      some of its physiological activities by acting as a potent inducer of interferon
      (IFN) gamma production by T and natural killer cells. IFN-gamma enhances the
      ability of the phagocytic cells to produce IL-12 and other proinflammatory
      cytokines. Thus, IL-12-induced IFN-gamma acts in a positive feedback loop that
      represents an important amplifying mechanism in the inflammatory response to
      infections. We show here that IFN-gamma enhances IL-12 production mostly by
      priming phagocytic cells for lipopolysaccharide (LPS)-induced transcription of
      the IL-12 p40 gene, which encodes the heavy chain of the IL-12 heterodimer;
      furthermore, IFN-gamma directly induces transcription of the IL-12 p35 gene,
      which encodes the light chain of IL-12, and has at least an additive effect with
      LPS stimulation in inducing its transcription. The priming effect of IFN-gamma on
      the LPS-induced p40 gene transcription requires preincubation of the cells with
      IFN-gamma for at least 8 h to obtain a maximal effect. The priming effect of IFN
      gamma for IL-12 production is predominantly at the transcriptional level for both
      the p40 and the p35 gene, and no evidence for a major role of posttranscriptional
      or translational mechanisms was found. A 3.3-kb human IL-12 p40 promoter
      construct transfected into cell lines recapitulated the tissue specificity of the
      endogenous gene, being silent in two human T cell lines, constitutively active in
      two human Epstein-Barr virus-positive B lymphoblastoid cell lines, and LPS
      inducible in the human THP-1 and mouse RAW264.7 monocytic cell lines. Because the
      RAW264.7 cell line is easily transfectable and regulates the endogenous IL-12 p40
      gene in response to IFN-gamma or LPS similarly to human monocytes, it was used
      for analysis of the regulation of the cloned human IL-12 p40 promoter. A
      requirement for the region between -222 and -204 in both LPS responsiveness and
      IFN-gamma priming was established. This region contains an ets consensus sequence
      that was shown to mediate activation of the promoter by IFN-gamma and LPS, as
      well as by a cotransfected ets-2. The -222 construct was also regulated in a
      tissue-specific manner. Two other elements, IRF-1 located at -730 to -719, and NF
      IL6 at -520 to -512, were also studied by deletion analysis, which did not result
      in decreased response to IFN-gamma and LPS stimulation.

PMID- 8551219
TI  - A novel function of CD40: induction of cell death in transformed cells.
AB  - CD40 is known as an important T-B cell interaction molecule which rescues B
      lymphocytes from undergoing apoptosis. Like other receptors of the tumor necrosis
      factor (TNF) receptor gene family, CD40 is expressed on cells of different tissue
      origins including some transformed cells. In contrast to its well-studied effects
      on B cells, the biological functions of CD40 in non-immune cells remain largely
      unknown. Here we show that CD40 ligation induces apoptotic cell death in
      transformed cells of mesenchymal and epithelial origin. This CD40-mediated cell
      death seems to use a preformed signaling pathway since it occurs even when
      protein synthesis is blocked. Notably, the CD40 cytoplasmic domain shares a
      structural homology with the recently defined "death domains" of the 55-kD TNF
      receptor (p55TNFR) and Fas. Despite these structural similarities, differences
      are seen in the way phorbol myristate acetate, interleukin 1, TNF, and various
      metabolic inhibitors influence the cellular responsiveness to CD40, p55TNFR, and
      Fas-mediated killing. Our study indicates that CD40 induces cell death by a
      distinct mechanism.

PMID- 8551220
TI  - The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic
      domain of CD2.
AB  - CD2, a cell surface glycoprotein expressed on T cells and natural killer cells,
      can couple to signaling pathways that result in T cell proliferation. An Src-like
      protein tyrosine kinase, p56lck, coprecipitates with CD2, and perturbation of CD2
      by monoclonal antibodies results in an increase in the activity of p56lck,
      suggesting that an interaction with p56lck contributes to CD2-mediated signaling.
      Herein, we investigate the mechanism by which CD2 associates with p56lck. We
      demonstrate that CD2 and p56lck associate when coexpressed in nonlymphoid cells,
      that this association requires the cytoplasmic domain of CD2, and that the SH3
      domain of p56lck mediates its interactions with CD2. Using truncation mutants of
      CD2, we identify two regions in the cytoplasmic domain of CD2 involved in binding
      p56lck. Each region contains a proline-rich sequence that, in the form of a
      synthetic peptide, directly binds p56lck. Thus, proline-rich sequences in the
      cytoplasmic domain of CD2 allow this transmembrane receptor to bind to the SH3
      domain of p56lck.

PMID- 8551221
TI  - CD16-mediated p21ras activation is associated with Shc and p36 tyrosine
      phosphorylation and their binding with Grb2 in human natural killer cells.
AB  - The Src homology (SH) 2/SH3 domain-containing protein Grb2 and the oncoprotein
      Shc have been implicated in a highly conserved mechanism that regulates p21ras
      activation. We investigated the involvement of these adaptor proteins in the
      signaling pathway induced by CD16 or interleukin (IL) 2R triggering in human
      natural killer (NK) cells. Both p46 and p52 forms of Shc were rapidly and
      transiently tyrosine phosphorylated upon CD16 or IL-2 stimulation with different
      kinetics. Shc immunoprecipitates from lysates of CD16- or IL-2-stimulated NK
      cells contained Grb2 and an unidentified 145-kD tyrosine phosphoprotein. Grb2
      immunoprecipitates from anti-CD16-stimulated NK cells contained not only Shc, but
      also a 36-kD tyrosine phosphoprotein (p36). The interaction between Grb2 and Shc
      or p36 occurred via the Grb2SH2 domain as indicated by in vitro binding assays
      using a bacteriologically synthesized glutathione S-transferase-Grb2SH2 fusion
      protein. We also present evidence that p21ras is activated by CD16 and IL-2R
      cross-linking. Accumulation of guanosine triphosphate-bound Ras was detected
      within 1 minute and occurred with kinetics similar to inductive protein tyrosine
      phosphorylation and Grb2 association of Shc and p36 adaptor proteins.

PMID- 8551222
TI  - A subpopulation of B220+ cells in murine bone marrow does not express CD19 and
      contains natural killer cell progenitors.
AB  - Bone marrow of both normal and rearrangement-deficient mice contains a small
      population of B220(CD45R)+ cells, which do not express the B lineage marker CD19.
      Instead, part of this population coexpresses the surface marker CD43 and lacks or
      expresses very low levels of heat stable antigen (HSA) and BP-1, thus
      representing a part of Hardy's fraction A (B220(+)-CD43+HSA-, BP-1-) of B lineage
      development. However, some 20-40% of these B220(+)-CD19- cells also coexpress the
      NK1.1 surface molecule and do not express genes like VpreB or B29 restricted to
      the B cell lineage. These cells respond to recombinant interleukin 2 in vitro,
      and develop into killer cells that can lyse the prototypic NK target tumor cell,
      YAC-1, as well as syngeneic normal lipopolysaccharide or concanavalin A blasts,
      providing they lack the surface expression of major histocompatibility complex
      class I molecules. The implications of these findings for studies on B
      lymphopoiesis are discussed. It is suggested that the CD19-specific monoclonal
      antibody is more reliable, as in humans, than B220(CD45R) to detect B lineage
      cells in mice.

PMID- 8551223
TI  - Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and
      lung damage in a mouse asthma model.
AB  - Airways inflammation is thought to play a central role in the pathogenesis of
      asthma. However, the precise role that individual inflammatory cells and
      mediators play in the development of airways hyperreactivity and the
      morphological changes of the lung during allergic pulmonary inflammation is
      unknown. In this investigation we have used a mouse model of allergic pulmonary
      inflammation and interleukin (IL) 5-deficient mice to establish the essential
      role of this cytokine and eosinophils in the initiation of aeroallergen-induced
      lung damage and the development of airways hyperreactivity. Sensitization and
      aerosol challenge of mice with ovalbumin results in airways eosinophilia and
      extensive lung damage analogous to that seen in asthma. Aeroallergen-challenged
      mice also display airways hyperreactivity to beta-methacholine. In IL-5-deficient
      mice, the eosinophilia, lung damage, and airways hyperreactivity normally
      resulting from aeroallergen challenge were abolished. Reconstitution of IL-5
      production with recombinant vaccinia viruses engineered to express this factor
      completely restored aeroallergen-induced eosinophilia and airways dysfunction.
      These results indicate that IL-5 and eosinophils are central mediators in the
      pathogenesis of allergic lung disease.

PMID- 8551224
TI  - Ig-specific T cell receptor-transgenic T cells are not deleted in the thymus and
      are functional in vivo.
AB  - The mechanisms that induce T cell tolerance to circulating self-proteins are
      still controversial, and both the deletion and selection of autoreactive T cells
      have been observed in the thymus of transgenic mouse models. To address the
      question of the induction of tolerance to circulating self-constituents, a T cell
      receptor-transgenic mouse specific for the serum protein immunoglobulin (Ig)
      gamma and (IgG2ab) was generated. The choice of an allotype-specific T cell also
      allowed the generation of transgenic control mice not expressing the self
      antigen. It was found that the transgenic T cells were not deleted in the thymus,
      did not become tolerant in the periphery, and regulated the function of gamma 2ab
      positive B cells as shown by the lack of IgG2ab protein in the serum of the
      transgenic mice. In spite of this activity in vivo, the transgenic T cells did
      not proliferate in vitro in response to the allotype-specific peptide.
      Interestingly, antigen-specific T cell proliferation could be restored if the
      transgenic mice were previously challenged to induce IgG2ab responses. After this
      challenge, IgG2ab protein in the serum of the transgenic mice could be partially
      restored, although still remaining much lower than in control mice. In addition,
      there was a dramatic increase in serum IgE levels, suggesting that newly
      generated gamma 2ab-secreting B cells can be induced to switch to IgE in the
      presence of allotype-specific T cells. These results indicate that Ig-specific T
      cells may represent a late-acting form of T cell help for the regulation of the
      IgG2a-to-IgE class switch.

PMID- 8551225
TI  - Cellular targets of infection and route of viral dissemination after an
      intravaginal inoculation of simian immunodeficiency virus into rhesus macaques.
AB  - We used the simian immunodeficiency virus (SIV)/rhesus macaque model to study
      events that underlie sexual transmission of human immunodeficiency virus type 1
      (HIV-1). Four female rhesus macaques were inoculated intravaginally with
      SIVmac251, and then killed 2, 5, 7, and 9 d later. A technique that detected
      polymerase chain reaction-amplified SIV in situ showed that the first cellular
      targets for SIV were in the lamina propria of the cervicovaginal mucosa,
      immediately subjacent to the epithelium. Phenotypic and localization studies
      demonstrated that many of the infected cells were likely to be dendritic cells.
      Within 2 d of inoculation, infected cells were identified in the paracortex and
      subcapsular sinus of the draining internal iliac lymph nodes. Subsequently,
      systemic dissemination of SIV was rapid, since culturable virus was detectable in
      the blood by day 5. From these results, we present a model for mucosal
      transmission of SIV and HIV-1.

PMID- 8551226
TI  - Bcl-2+ tonsillar plasma cells are rescued from apoptosis by bone marrow
      fibroblasts.
AB  - Plasma cells represent the final stage of B lymphocyte differentiation. Most
      plasma cells in secondary lymphoid tissues live for a few days, whereas those in
      the lamina propria of mucosa and in bone marrow live for several weeks. To
      investigate the regulation of human plasma cell survival, plasma cells were
      isolated from tonsils according to high CD38 and low CD20 expression. Tonsillar
      plasma cells express CD9, CD19, CD24, CD37, CD40, CD74, and HLA-DR, but not CD10,
      HLA-DQ, CD28, CD56, and Fas/CD95. Although plasma cells express intracytoplasmic
      Bcl-2, they undergo swift apoptosis in vitro and do not respond to CD40
      triggering. Bone marrow fibroblasts and rheumatoid synoviocytes, however,
      prevented plasma cells from undergoing apoptosis in a contact-dependent fashion.
      These data indicate that fibroblasts may form a microenvironment favorable for
      plasma cell survival under normal and pathological conditions.

PMID- 8551227
TI  - Distinct populations of dendritic cells are present in the subepithelial dome and
      T cell regions of the murine Peyer's patch.
AB  - Despite the fact that the Peyer's patch (PP) is the primary site for antigen
      uptake in the intestine, the cellular basis of antigen handling after transport
      into the PP is poorly understood. We performed immunohistology of murine PPs
      using the dendritic cell (DC)-reactive monoclonal antibodies N418, NLDC-145,
      M342, and 2A1, as well as antibodies to other T cell, B cell, and macrophage
      markers. N418+, 2A1+, NLDC-145-, M342- cells form a dense layer of cells in the
      subepithelial dome (SED), just beneath the follicle epithelium, and are scattered
      throughout the follicle, sparing the germinal center. In contrast, N418+, 2A1+,
      NLDC-145+, and M342+ DCs are present in the interfollicular T cell regions (IFR).
      CD3+ and CD4+, but no CD8+ T cells were present in the SED and the follicle,
      including the germinal center, while CD3+, CD4+, and CD8+ T cells were present in
      the IFR. B cells and macrophages were poorly represented in the SED as no B220+
      cells, only few Mac-1lo cells, and no F4/80+ cells were present at this site. In
      contrast, Mac-1hi cells were found in the IFR and lamina propria of intestinal
      villi, while F4/80+ cells were found only in the latter. In further phenotypic
      studies, we analyzed surface molecules of PP and spleen DCs by flow cytometry and
      found that these cells had similar fluorescence profiles when stained with N418,
      NLDC-145, and 33D1 DC-reactive antibodies, and antibodies to the costimulatory
      molecules B7-1 (1G10) and B7-2 (GL1). In contrast, PP DCs expressed 5-10-fold
      higher levels of major histocompatibility complex class II antigens (IEk) than
      spleen DCs. Finally, in functional studies, we demonstrated that both PP and
      spleen DCs process soluble protein antigens during overnight culture and induce
      similar levels of proliferation in CD3+ T cells, and CD4+/Mel 14hi T cells from T
      cell receptor transgenic mice. The in vivo relevance of such presentation was
      shown by the fact that PP DCs isolated from Balb/c mice after being fed ovalbumin
      stimulated proliferation in ovalbumin T cell receptor T cells. Taken together,
      our data suggest that DCs in the SED of the PP are uniquely positioned for the
      processing of antigens passed into the PP from the overlying M cell, and that PP
      DCs are effective at processing and presenting oral antigens to naive T cells.

PMID- 8551228
TI  - The extracellular domain of CD45 controls association with the CD4-T cell
      receptor complex and the response to antigen-specific stimulation.
AB  - The CD45 tyrosine phosphatase plays an important role in regulating T lymphocyte
      activation, but the function of the different isoforms of CD45 is not known. T
      cell transfectants have been prepared that express individual CD45 isoforms in
      cells with a well-defined T cell receptor (TCR) from the D10 T helper 2 clone. We
      find that cells bearing low molecular weight CD45 isoforms are far more efficient
      in responding to stimulation with peptide and antigen-presenting cells compared
      with cells bearing high molecular weight CD45 isoforms. One hypothesis for the
      preferential activation of cells that express low molecular weight CD45 isoforms
      is that they interact with other cell surface antigens important in TCR
      signaling, altering their phosphorylation status and affecting the character of
      the signal transduction pathway. In this report, using cells expressing single
      isoforms, we demonstrate that low molecular weight isoforms of CD45
      preferentially associate with CD4 and the TCR complex compared with high
      molecular weight isoforms. The molecular basis for this interaction was further
      examined using a glycosyl phosphatidyl inositol (GPI)-linked form of CD45Null
      (lacking tyrosine phosphatase domains), which preferentially associated with CD4
      compared with GPI-linked CD45ABC, and cytoplasmic tail mutants of CD4, which
      retained the ability to coassociate. Using this panel of transfectants, it is
      clear that the interaction between CD4 and CD45 does not require the cytoplasmic
      domains of CD45, but is dependent on the specific external domain of the various
      isoforms: low molecular weight species were more likely to associate with the CD4
      TCR complex than the higher molecular weight isoforms, and their ability to
      coassociate correlated with the magnitude of the response to specific antigen.

PMID- 8551229
TI  - Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo:
      exploration of the paradox of the early immune response to outer surface proteins
      A and C in Lyme disease.
AB  - The outer surface proteins (Osps) of Borrelia burgdorferi, the etiologic agent of
      Lyme disease, are principle targets of protective immune responses against this
      organism. Whereas most North American strains of B. burgdorferi in culture
      express an abundant amount of Osp A, antibodies to this protein are either absent
      or only weakly detected in the sera of naturally infected patients or
      experimentally infected mice. In contrast, Osp C, which has variable expression
      on cultured organisms; elicits an early, strong humoral response. To examine this
      paradox, we have studied the in vivo adaptation of a cloned population of B.
      burgdorferi strain N40 during the early course of experimental murine
      borreliosis. As in human disease, antibodies to Osp A were only weakly present in
      the early immune repertoire after murine inoculation with low dose (10(3))
      spirochetes. In contrast, antibodies to Osp C were prominent, even though on
      cultured spirochetes Osp C mRNA and protein expression could not be detected by
      reverse transcription polymerase chain reaction (RT-PCR) or indirect
      immunofluorescence, respectively. These observations led us to investigate the
      expression of Osp A and Osp C in vivo. By direct fluorescent staining of
      uncultured spirochetes ex vivo and by PCR amplification of spirochetal mRNA, we
      show that Osp C is indeed expressed by some spirochetes after infection in the
      mouse. Spirochetes expressing Osp A could also be detected within the first 2 wk
      of infection, but not at 30 d. Osp A mRNA, although present at day 14 of
      infection, could not be amplified by RT-PCR at day 30, suggesting that the
      expression of this Osp is transient. This further implies that the late burst in
      Osp A antibodies in both mice and humans may be anamnestic. These results
      indicate that either Osp C is upregulated on spirochetes after infection, or Osp
      C-expressing spirochetes expand preferentially over those expressing Osp A during
      infection. These results have important implications for vaccine design and offer
      one explanation for the failure of Osp A antibodies to eradicate spirochetes from
      the infected host.

PMID- 8551230
TI  - HLA-DQ8 transgenic mice are highly susceptible to collagen-induced arthritis: a
      novel model for human polyarthritis.
AB  - Genetic studies have indicated that susceptibility to rheumatoid arthritis (RA)
      maps to the HLA-DR locus of the major histocompatibility complex. Strong linkage
      disequilibrium between certain HLA-DQ genes and HLA-DR genes associated with RA,
      however, suggests that HLA-DQ molecules may also play a role in RA
      susceptibility. To examine the role of HLA-DQ molecules in arthritis, we
      generated transgenic mice expressing the DQA1*0301 and DQB1*0302 genes from an RA
      predisposing haplotype (DQ8/DR4Dw4). The transgenes were introduced into mouse
      class II-deficient H-2Ab0 mice, and their susceptibility to experimental collagen
      induced arthritis was evaluated. The HLA-DQ8+,H-2Ab0 mice displayed good
      expression of the DQ8 molecule, while no surface expression of endogenous murine
      class II molecules could be detected. The DQ8 molecule also induced the selection
      of CD4+ T cells expressing a normal repertoire of V beta T cell receptors.
      Immunization of HLA-DQ8+,H-2Ab0 mice with bovine type II collagen (CII) induced a
      strong antibody response that was cross-reactive to homologous mouse CII. Also,
      in vitro proliferative responses against bovine CII, which were blocked in the
      presence of an antibody specific for HLA-DQ and mouse CD4, were detected.
      Finally, a severe polyarthritis developed in a majority of HLA-DQ8+,H-2Ab0 mice,
      which was indistinguishable from the disease observed in arthritis susceptible
      B10.T(6R) (H-2Aq) controls. In contrast, HLA-DQ8-,H-2Ab0 fullsibs did not
      generate CII antibody and were completely resistant to arthritis. Therefore,
      these results strongly suggest that HLA-DQ8 molecules contribute to genetic
      susceptibility to arthritis and also establish a novel animal model for the study
      of human arthritis.

PMID- 8551231
TI  - Borrelia burgdorferi OspA is an arthropod-specific transmission-blocking Lyme
      disease vaccine.
AB  - Borrelia burgdorferi, the spirochetal agent of Lyme disease, is transmitted by
      Ixodes ticks. A vaccine based on B. burgdorferi outer surface protein (Osp) A
      protects mice from spirochete infection. Here we report on the expression of OspA
      on spirochetes inside engorging ticks and relate OspA expression to
      antispirochetal immunity. Spirochetes in the gut of unfed nymphal ticks were
      stained by an OspA antibody, whereas in feeding ticks, the majority of
      spirochetes in the gut and salivary glands did not stain with the antibody. Thus,
      OspA was not expressed on most spirochetes during transmission from the vector to
      the vertebrate host. To examine the mechanism of protection afforded by OspA
      antibody, mice were passively immunized with OspA antibody at different times
      relative to tick attachment. When OspA antibody was administered to mice before
      or at the time of tick attachment, spirochetal development events in the vector,
      such as growth and salivary gland invasion, were blocked and the mice were
      protected from B. burgdorferi infection. When OspA antibody was administered to
      mice 48 h after tick attachment, spirochetes persisted in the nymphs and the mice
      were not protected despite the presence of circulating antibodies in the host as
      well as in the tick blood meal. Thus, OspA immunity appears to be effective only
      during a narrow window time at the beginning of the blood meal when antibodies
      bind to OspA-expressing spirochetes in the tick gut and block transmission from
      the vector to the host.

PMID- 8551232
TI  - An essential role for macrophage migration inhibitory factor in the tuberculin
      delayed-type hypersensitivity reaction.
AB  - 30 years ago, investigations into the molecular basis of the delayed-type
      hypersensitivity reaction (DTH) provided evidence for the first lymphokine
      activity: a lymphocyte-derived mediator called macrophage migration inhibitory
      factor (MIF), which inhibited the random migration of peritoneal macrophages.
      Despite the long-standing association of MIF with the DTH reaction and the
      cloning of a human protein with macrophage migration inhibitory activity, the
      precise role of MIF in this classic cell-mediated immune response has remained
      undefined. This situation has been further complicated by the fact that two other
      cytokines, interferon gamma and IL-4, similarly inhibit macrophage migration and
      by the identification of mitogenic contaminants in some preparations of cloned
      human MIF. Using recently developed molecular probes for mouse MIF, we have
      examined the role of this protein in a classical model of DTH, the tuberculin
      reaction in mice. Both MIF messenger RNA and protein were expressed prominently
      in DTH lesions, as assessed by reverse transcription polymerase chain reaction,
      in situ hybridization, and immunostaining with anti-MIF antibody. The predominant
      cellular origin of MIF appeared to be the monocyte/macrophage, a cell type
      identified recently to be a major source of MIF release in vivo. The
      administration of neutralizing anti-MIF antibodies to mice inhibited
      significantly the development of DTH, thus affirming the central role of MIF in
      this classic immunological response.

PMID- 8551233
TI  - Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective
      tumor immunity.
AB  - Cytotoxic T lymphocytes (CTLs) are a critical component of the immune response to
      tumors. Tumor-derived peptide antigens targeted by CTLs are being defined for
      several human tumors and are potential immunogens for the induction of specific
      antitumor immunity. Dendritic cells (DC) are potent antigen-presenting cells
      (APCs) capable of priming CTL responses in vivo. Here we show that major
      histocompatibility complex class I-presented peptide antigen pulsed onto
      dendritic APCs induces protective immunity to lethal challenge by a tumor
      transfected with the antigen gene. The immunity is antigen specific, requiring
      expression of the antigen gene by the tumor target, and is eliminated by in vivo
      depletion of CD8+ T cells. Furthermore, mice that have rejected the transfected
      tumor are protected from subsequent challenge with the untransfected parent
      tumor. These results suggest that immunization strategies using antigen-pulsed DC
      may be useful for inducing tumor-specific immune responses.

PMID- 8551234
TI  - Regulation of T cell receptor delta gene rearrangement by c-Myb.
AB  - Developmental activation of VDJ recombination at the T cell receptor (TCR) delta
      locus is controlled by an intronic transcriptional enhancer (E delta).
      Transcriptional activation by E delta is dependent on c-Myb. To determine whether
      c-Myb plays a role in the activation of TCR-delta gene rearrangement, we compared
      VDJ recombination in transgenic mice carrying two versions of a human TCR-delta
      gene minilocus recombination substrate. One includes a wild-type E delta, whereas
      the other carries an E delta with a mutation that abrogates c-Myb binding. We
      demonstrate that an intact Myb binding site is necessary for efficient
      rearrangement of the minilocus substrate, suggesting that c-Myb plays a crucial
      role in activating VDJ recombination at the endogenous TCR-delta locus.

PMID- 8551235
TI  - HCC-1, a novel chemokine from human plasma.
AB  - A novel CC chemokine, HCC-1, was isolated from the hemofiltrate of patients with
      chronic renal failure. HCC-1 has a relative molecular mass of 8,673 and consists
      of 74 amino acids including four cysteines linked to disulfide bonds. HCC-1 cDNA
      was cloned from human bone marrow and shown to code for the mature protein plus a
      putative 19-residue leader sequence. Mature HCC-1 has sequence identity of 46%
      with macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, and 29-37%
      with the other human CC chemokines. Unlike MIP-1 alpha and the other CC
      chemokines, HCC-1 is expressed constitutively in several normal tissues (spleen,
      liver, skeletal and heart muscle, gut, and bone marrow), and is present at high
      concentrations (1-80 nM) in plasma. HCC-1 has weak activities on human monocytes
      and acts via receptors that also recognize MIP-1 alpha. It induced intracellular
      Ca2+ changes and enzyme release, but no chemotaxis, at concentrations of 100
      1,000 nM, and was inactive on T lymphocytes, neutrophils, and eosinophil
      leukocytes. In addition, HCC-1 enhanced the proliferation of CD34+ myeloid
      progenitor cells. It was as effective as MIP-1 alpha, but about 100-fold less
      potent.

PMID- 8551236
TI  - Association of tyrosine protein kinase Zap-70 with the protooncogene product
      p120c-cbl in T lymphocytes.
AB  - Accumulating data show that the tyrosine protein kinase Zap-70 plays an essential
      role in T cell receptor-mediated signal transduction. However, the model of
      action, as well as the physiologically relevant substrates of Zap-70, have not
      been determined. We have attempted to identify a 120-kD tyrosine-phosphorylated
      protein (p120) that associates with Zap-70 in activated T lymphocytes. The
      results of our analyses showed that p120 is largely encoded by the c-cbl
      protooncogene. Furthermore, the association of Zap-70 with c-Cbl was shown to be
      induced by T cell receptor stimulation, implying that it required
      posttranslational modification of one or both of these products. FynT, but not
      Lck, also associated with c-Cbl in activated T cells. Finally, using a
      heterologous system, it was demonstrated that the ability of Zap-70 to cause
      tyrosine phosphorylation of p120c-cbl was dependent on Lck- or FynT-mediated
      signals. As c-Cbl can associate with several other signaling molecules, it may
      couple Zap-70 to downstream effectors during T cell activation.

PMID- 8551237
TI  - Efficient destruction of human immunodeficiency virus in human serum by
      inhibiting the protective action of complement factor H and decay accelerating
      factor (DAF, CD55).
AB  - Activation of the human complement system leads to complement deposition on human
      immunodeficiency virus (HIV) and HIV-infected cells without causing efficient
      complement-mediated lysis. Even in the presence of HIV-specific antibodies, only
      a few particles are destroyed, demonstrating that HIV is intrinsically resistant
      to human complement. Here we report that, in addition to decay accelerating
      factor (DAF) being partially responsible, human complement factor H (CFH), a
      humoral negative regulator of complement activation, is most critical for this
      resistance. In the presence of HIV-specific antibodies, sera devoid of CFH (total
      genetic deficiency or normal human serum depleted of CFH by affinity
      chromatography) lysed free virus and HIV-infected but not uninfected cells. In
      the presence of CFH, lysis of HIV was only obtained when binding of CFH to gp41
      was inhibited by a monoclonal antibody against a main CFH-binding site in gp41.
      Since CFH is an abundant protein in serum, and high local concentration of CFH
      can be obtained at the surface of HIV as the result of specific interactions of
      CFH with the HIV envelope, it is proposed that the resistance of HIV and HIV
      infected cells against complement-mediated lysis in vivo is dependent on DAF and
      CFH and can be overcome by suppressing this protection. Neutralization of HIV may
      be achieved by antibodies against DAF and, more importantly, antibodies against
      CFH-binding sites on HIV envelope proteins.

PMID- 8551238
TI  - Interleukin (IL)-6 gene expression in the central nervous system is necessary for
      fever response to lipopolysaccharide or IL-1 beta: a study on IL-6-deficient
      mice.
AB  - Interleukin (IL)-6, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) are
      considered to act as endogenous pyrogens. Because of the complex pattern of cross
      inductions between these cytokines, the relative role of the central and
      peripheral production of these cytokines in eliciting the fever response has not
      yet been clarified. The purpose of this study was to determine the role of IL-6
      in the fever response by making use of mice carrying a null mutation in the IL-6
      gene. The intraperitoneal injections of lipopolysaccharide (LPS) (50
      micrograms/kg) and recombinant murine (rm) IL-1 beta (10 micrograms/kg),
      respectively, failed to evoke fever response in IL-6-deficient mice, whereas the
      same doses of LPS and rmIL-1 beta caused fever response in wild-type mice. The
      fever response could be induced in the IL-6-deficient mice by
      intracerebroventricular injection of recombinant human (rh) IL-6 (500 ng/mouse),
      whereas intracerebroventricular injection of rmIL-1 beta (100 ng/mouse) failed to
      produce fever response in the IL-6-deficient mice. These results suggest that
      central IL-6 is a necessary component of the fever response to both endogenous
      (IL-1 beta) and exogenous (LPS) pyrogens in mice and that IL-6 acts downstream
      from both peripheral and central IL-1 beta.

PMID- 8551239
TI  - Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T
      lymphocytes against tumor antigen in vivo.
AB  - The priming of an immune response against a major histocompatibility complex
      class I-restricted antigen expressed by nonhematopoietic cells involves the
      transfer of that antigen to a host bone marrow-derived antigen presenting cell
      (APC) for presentation to CD8+ T lymphocytes. Dendritic cells (DC), as bone
      marrow-derived APC, are first candidates for presentation of tumor-associated
      antigens (TAA). The aim of this study was to see whether DC are able to prime in
      vivo antigen-specific cytotoxic T lymphocytes after exposure to a soluble protein
      antigen in vitro. Lacking a well-defined murine TAA, we took advantage of beta
      galactosidase (beta-gal)-transduced tumor cell lines as a model in which beta-gal
      operationally functions as TAA. For in vivo priming both a DC line, transduced or
      not transduced with the gene coding for murine GM-CSF, and fresh bone marrow
      derived DC (bm-DC), loaded in vitro with soluble beta-gal, were used. Priming
      with either granulocyte macrophage colony-stimulating factor-transduced DC line
      or fresh bm-DC but not with untransduced DC line generated CTL able to lyse beta
      gal-transfected target cells. Furthermore, GM-CSF was necessary for the DC line
      to efficiently present soluble beta-gal as an H-2Ld-restricted peptide to a beta
      gal-specific CTL clone. Data also show that a long-lasting immunity against tumor
      challenge can be induced using beta-gal-pulsed bm-DC as vaccine. These results
      indicate that effector cells can be recruited and activated in vivo by antigen
      pulsed DC, providing an efficient immune reaction against tumors.

PMID- 8551240
TI  - Variation of gonococcal lipooligosaccharide structure is due to alterations in
      poly-G tracts in lgt genes encoding glycosyl transferases.
AB  - The lipooligosaccharide (LOS) expressed by gonococci spontaneously varies its
      structure at high frequency, but the underlying genetic mechanism has not been
      described. We have previously reported that the genes encoding the glycosyl
      transferases responsible for the biosynthesis of the variable alpha chain of the
      LOS of Neisseria gonorrhoeae are located in a locus containing five genes, lgtA,
      lgtB, lgtC, lgtD, and lgtE. Sequence analysis showed that lgtA, lgtC, and lgtD
      contained poly-G tracts within the coding frames, leading to the hypothesis that
      shifts in the number of guanosine residues in the poly-G tracts might be
      responsible for the high frequency variation in structure of gonococcal LOS. We
      now provide experimental evidence confirming this hypothesis.

PMID- 8551241
TI  - Immunoglobulin-mediated signal transduction in B cells from CD45-deficient mice.
AB  - CD45 expression is essential for immunoglobulin (Ig)-mediated B cell activation.
      Treatments with either anti-Ig or anti-CD45 suggest that CD45 may facilitate
      early signaling events such as calcium mobilization, and phosphoinositide
      hydrolyis as well as later events leading to transcription of genes such as c
      myc. To examine the role of CD45 more extensively, CD45-deficient mice were
      generated by disruption of exon 6. Although normal numbers of B cells were found
      in peripheral lymphoid tissues, CD45-deficient cells failed to proliferate upon
      IgM crosslinking. In the present study, we demonstrate that the fraction of high
      buoyant density B cells is reduced while low buoyant density cells are increased.
      Moreover, there is a significant decline in the number of splenic B cells of the
      mature IgDhi, IgMlo phenotype. Although both the basal and anti-Ig-induced levels
      of phosphorylation of Ig-alpha and phospholipase C gamma 2 are indistinguishable
      from that observed in CD45+ control B cells, a major distinction was found in
      Ca2+ mobilization. While anti-Ig-induced mobilization of intracellular Ca2+
      stores was normal, influx from extracellular sources was abrogated. This finding
      reveals a novel pathway of regulating B cell responses mediated by CD45.

PMID- 8551242
TI  - HIV-induced apoptosis requires the CD4 receptor cytoplasmic tail and is
      accelerated by interaction of CD4 with p56lck.
AB  - The roles of the CD4 receptor and the src kinase p56lck were examined in the
      process of HIV-induced apoptosis of CD4+ T lymphocytes. The presence of the CD4
      cytoplasmic tail was found to be essential in delivering an apoptotic signal, and
      interaction of CD4 with p56lck potentiated HIV-induced apoptosis. Apoptosis, but
      not HIV replication, was abrogated by deleting the NH2-terminal intracytoplasmic
      tail of CD4, or by mutating the two critical cysteines in this tail that are
      responsible for CD4-p56lck interaction. Introduction of p56lck in C8166-45 or MT
      2 cells, CD4+ T cell lines deficient for this protein, greatly increased HIV
      induced apoptosis and syncytium formation. The ability of p56lck to deliver an
      apoptotic signal did not depend on its kinase function, since a kinase-deficient
      mutant was as effective as its normal counterpart in inducing apoptosis,
      suggesting that p56lck may act as an adapter to anchor other proteins to
      transduce the death signal.

PMID- 8551243
TI  - Transgenic mice expressing the human high-affinity immunoglobulin (Ig) E receptor
      alpha chain respond to human IgE in mast cell degranulation and in allergic
      reactions.
AB  - The high-affinity receptor for immunoglobulin (Ig) E (Fc epsilon RI) on mast
      cells and basophils plays a key role in IgE-mediated allergies. Fc epsilon RI is
      composed of one alpha, one beta, and two gamma chains, which are all required for
      cell surface expression of Fc epsilon RI, but only the alpha chain is involved in
      the binding to IgE. Fc epsilon RI-IgE interaction is highly species specific, and
      rodent Fc epsilon RI does not bind human IgE. To obtain a "humanized" animal
      model that responds to human IgE in allergic reactions, transgenic mice
      expressing the human Fc epsilon RI alpha chain were generated. The human Fc
      epsilon RI alpha chain gene with a 1.3-kb promoter region as a transgene was
      found to be sufficient for mast cell-specific transcription. Cell surface
      expression of the human Fc epsilon RI alpha chain was indicated by the specific
      binding of human IgE to mast cells from transgenic mice in flow cytometric
      analyses. Expression of the transgenic Fc epsilon RI on bone marrow-derived mast
      cells was 4.7 x 10(4)/cell, and the human IgE-binding affinity was Kd = 6.4 nM in
      receptor-binding studies using 125I-IgE. The transgenic human Fc epsilon RI alpha
      chain was complexed with the mouse beta and gamma chains in immunoprecipitation
      studies. Cross-linking of the transgenic Fc epsilon RI with human IgE and
      antigens led to mast cell activation as indicated by enhanced tyrosine
      phosphorylation of the Fc epsilon RI beta and gamma chains and other cellular
      proteins. Mast cell degranulation in transgenic mice could be triggered by human
      IgE and antigens, as demonstrated by beta-hexosaminidase release in vitro and
      passive cutaneous anaphylaxis in vivo. The results demonstrate that the human Fc
      epsilon RI alpha chain alone not only confers the specificity in human IgE
      binding, but also can reconstitute a functional receptor by coupling with the
      mouse beta and gamma chains to trigger mast cell activation and degranulation in
      a whole animal system. These transgenic mice "humanized" in IgE-mediated
      allergies may be valuable for development of therapeutic agents that target the
      binding of IgE to its receptor.

PMID- 8551244
TI  - Absence of trauma-induced leukocyte rolling in mice deficient in both P-selectin
      and intercellular adhesion molecule 1.
AB  - Leukocyte recruitment during inflammation is achieved through a multistep
      paradigm that includes margination, selectin-mediated rolling, beta 2 integrin
      mediated firm adhesion, emigration, and migration into the site of inflammation.
      We have used the mouse cremaster muscle as a model of trauma- and cytokine
      induced inflammation to study the possible role of intercellular adhesion
      molecule (ICAM) 1 in leukocyte rolling using gene-targeted mice deficient in ICAM
      1, P-selectin, and a combination of P-selectin and ICAM-1. Rolling flux and
      average leukocyte rolling velocity in ICAM-1-deficient mice was not different
      from wild-type mice, but P-selectin/ICAM-1-deficient mice showed a total absence
      of rolling for at least 2 h after surgical trauma. Rolling in both wild-type and
      ICAM-1-deficient mice 60-120 min after trauma was significantly inhibited by a P
      selectin monoclonal antibody (mAb) (RB40.34). In contrast, an mAb (KAT-1)
      blocking ICAM-1 binding to leukocyte function-associated antigen 1 did not block
      residual rolling in P-selectin-deficient mice. TNF-alpha induced leukocyte
      rolling in P-selectin/ICAM-1-deficient mice, but the rolling flux fraction was
      significantly lower than in TNF-alpha-treated ICAM-1-deficient mice. Leukocyte
      rolling in P-selectin/ICAM-1-deficient mice treated with TNF-alpha for 3 h was
      completely blocked by an E-selectin mAb (9A9E3), and partially by an L-selectin
      mAb (MEL-14). This clearly demonstrates E-selectin-dependent rolling in vivo.
      Leukocyte rolling velocities were significantly reduced after TNF-alpha treatment
      and were similar in wild-type and gene-targeted strains. We conclude that the
      residual trauma-induced leukocyte rolling seen in P-selectin-deficient mice is
      completely abolished by concomitant ICAM-1 deficiency. This severe defect in
      leukocyte rolling may explain the absence of leukocyte recruitment into the
      inflamed peritoneal cavity of P-selectin/ICAM-1-deficient mice at early time
      points (< or = 4 h).

PMID- 8551245
TI  - CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid
      onset of diabetes in NOD mice in the absence of CD4 cells.
AB  - T cells play an important role in the pathogenesis of diabetes in the nonobese
      diabetic (NOD) mouse. CD8 cytotoxic T cell lines and clones were generated from
      the lymphocytic infiltrate in the islets of Langerhans of young (7-wk-old). NOD
      mice by growing them on (NOD x B6-RIP-B7-1)F1 islets. These cells proliferate
      specifically to NOD islets and kill NOD islets in vitro. The cells are restricted
      by H-2Kd, and all bear T cell antigen receptor encoded by V beta 6. When these
      CD8 T cell lines and clones are adoptively transferred to irradiated female NOD,
      young NOD-SCID, and CB17-SCID mice, diabetes occurs very rapidly, within 10 d of
      transfer and without CD4 T cells.

PMID- 8551246
TI  - Dendritic cells as adjuvants for class I major histocompatibility complex
      restricted antitumor immunity.

PMID- 8551247
TI  - CD40 and B cell antigen receptor dual triggering of resting B lymphocytes turns
      on a partial germinal center phenotype.
AB  - Phenotypic alterations occur when resting human B lymphocytes become germinal
      center (GC) cells. These include the induction of surface CD38, CD95 (FAS/APO-1),
      and carboxy-peptidase-M (CPM), a recently described GC marker. However, the
      factors that govern the in vivo induction of these surface molecules on B cells
      remain unknown. Here, we purified resting (CD38-) human B lymphocytes from
      tonsils in an attempt to establish culture conditions resulting in the induction
      of these three GC markers. We show that interferon (IFN) alpha or IFN-gamma, as
      well as antibodies against the B cell antigen receptor (BCR), could induce CD38
      on resting B lymphocytes, a phenomenon further enhanced by CD40 stimulation.
      Concomitantly, CD95 was upregulated by CD40 ligation and, to a lesser extent, by
      IFN-gamma. By contrast, CPM expression could be upregulated only through BCR
      triggering. This CPM induction was specifically enhanced by CD19 or CD40
      ligation. CD40 + BCR stimulation of resting B cells with CD40 ligand-transfected
      fibroblastic cells in the presence of cross-linked anti-BCR monoclonal antibodies
      resulted in the coexpression of CD38, CD95, and CPM. As GC cells, these cells
      also expressed CD71, CD80 (B7.1), and CD86 (B7.2), but not CD24. However, CD10+
      or CD44- B cells could not be detected in these culture conditions, suggesting
      that yet other signals are required for the induction of these GC markers.
      Consistent with a GC phenotype, CD40 + BCR-stimulated cells exhibited reduced
      viability when cultured for 20 h in the absence of stimulus. These results first
      demonstrate that cotriggering of resting B cells through BCR and CD40 induces
      both phenotypic and functional GC features. They also show that IFN and CD19
      triggering of resting B cells specifically modulate the expression of GC markers.

PMID- 8551248
TI  - Therapy of murine tumors with tumor peptide-pulsed dendritic cells: dependence on
      T cells, B7 costimulation, and T helper cell 1-associated cytokines.
AB  - Antigen presentation by host dendritic cells (DC) is critical for the initiation
      of adaptive immune responses. We have previously demonstrated in immunogenic
      murine tumor models that bone marrow (BM)-derived DC pulsed ex vivo with
      synthetic tumor-associated peptides, naturally expressed by tumor cells, serve as
      effective antitumor vaccines, protecting animals against an otherwise lethal
      tumor challenge (Mayordomo, J.I., T. Zorina, W.J. Storkus, C. Celluzzi, L.D.
      Falo, C.J. Melief, T. Ildstad, W.M. Kast, A.B. DeLeo, and M.T. Lotze. 1995.
      Nature Med. 1:1297-1302). However, T cell-defined epitopes have not been
      identified for most human cancers. To explore the utility of this approach in the
      treatment of tumors expressing as yet uncharacterized epitopes, syngeneic
      granulocyte/macrophage colony-stimulating factor-stimulated and BM-derived DC,
      pulsed with unfractionated acid-eluted tumor peptides (Storkus, W.J., H.J. Zeh
      III, R.D. Salter, and M.T. Lotze. 1993. J. Immunother. 14:94-103) were used to
      treat mice bearing spontaneous, established tumors. The adoptive transfer of 5 x
      10(5) tumor peptide-pulsed DC dramatically suppressed the growth of weakly
      immunogenic tumors in day 4 to day 8 established MCA205 (H-2b) and TS/A (H-2d)
      tumor models, when applied in three biweekly intravenous injections. Using the
      immunogenic C3 (H-2b) tumor model in B6 mice, tumor peptide-pulsed DC therapy
      resulted in the erradication of established d14 tumors and long-term survival in
      100% of treated animals. The DC-driven antitumor immune response was primarily
      cell mediated since the transfer of spleen cells, but not sera, from immunized
      mice efficiently protected sublethally irradiated naive mice against a subsequent
      tumor challenge. Furthermore, depletion of either CD4+ or CD8+ T cells from tumor
      bearing mice before therapy totally suppressed the therapeutic efficacy of DC
      pulsed with tumor-derived peptides. Costimulation of the host cell-mediated
      antitumor immunity was critical since inoculation of the chimeric fusion protein
      CTLA4-Ig virtually abrogated the therapeutic effects of peptide-pulsed DC in
      vivo. The analysis of the cytokine pattern in the draining lymph nodes and
      spleens of tumor-bearing mice immunized with DC pulsed with tumor-eluted peptides
      revealed a marked upregulation of interleukin (IL) 4 and interferon (IFN) gamma
      production, as compared with mice immunized with DC alone or DC pulsed with
      irrelevant peptides. DC-induced antitumor effects were completely blocked by
      coadministration of neutralizing monoclonal antibody directed against T helper
      cell 1-associated cytokines (such as IL-12, tumor necrosis factor alpha, IFN
      gamma), and eventually, but not initially, blocked by anti-mIL-4 mAb. Based on
      these results, we believe that DC pulsed with acid-eluted peptides derived from
      autologous tumors represents a novel approach to the treatment of established,
      weakly immunogenic tumors, and serves as a basis for designing clinical trials in
      cancer patients.

PMID- 8551249
TI  - Inhibition of purified CD34+ hematopoietic progenitor cells by human
      immunodeficiency virus 1 or gp120 mediated by endogenous transforming growth
      factor beta 1.
AB  - Human CD34+ hematopoietic progenitor cells, stringently purified from the
      peripheral blood of 20 normal donors, showed an impaired survival and clonogenic
      capacity after exposure to either heat-inactivated human immunodeficiency virus
      (HIV) 1 (strain IIIB) or cross-linked envelope gp120. Cell cycle analysis,
      performed at different times in serum-free liquid culture, showed an accumulation
      in G0/G1 in HIV-1- or gp120-treated cells and a progressive increase of cells
      with subdiploid DNA content, characteristic of apoptosis. In blocking experiments
      with anti-transforming growth factor (TGF) beta 1 neutralizing serum or TGF-beta
      1 oligonucleotides, we demonstrated that the HIV-1- or gp120-mediated suppression
      of CD34+ cell growth was almost entirely due to an upregulation of endogenous TGF
      beta 1 produced by purified hematopoietic progenitors. Moreover, by using a
      sensitive assay on the CCL64 cell line, increased levels of bioactive TGF-beta 1
      were recovered in the culture supernatant of HIV-1/gp120-treated CD34+ cells.
      Anti-TGF-beta 1 neutralizing serum or TGF-beta 1 oligonucleotides were also
      effective in inducing a significant increase of the plating efficiency of CD34+
      cells, purified from the peripheral blood of three HIV-1-seropositive
      individuals, suggesting that a similar mechanism may be also operative in vivo.
      The relevance of these findings to a better understanding of the pathogenesis of
      HIV-1-related cytopenias is discussed.

PMID- 8551250
TI  - Relative frequency of human rotavirus VP4 (P) genotypes recovered over a ten-year
      period from South African children with diarrhea.
AB  - The relative frequency and distribution of the VP4 (P) genotypes of 227 human
      rotavirus field strains were investigated in South Africa. The stool samples were
      collected between 1984-1993 from infants and young children with diarrhea at Ga
      Rankuwa Hospital, Pretoria, South Africa. The RNA was extracted from stools, heat
      denatured, and dot blotted onto nylon membranes. The blots were hybridized to PCR
      generated, 32P radio-labelled VP4-specific probes (corresponding to the
      hyperdivergent region of the VP4 gene) of the following human rotavirus VP4
      genotypes: P4, P6, P8, P9, P10, and P12. Of the 157 rotavirus strains typed by
      the probes, the P8 genotype was identified most frequently in 63.7% (n = 100) of
      the samples. The P4 and P6 genotypes were detected less frequently in 22.3% (n =
      35) and 8.3% (n = 13) of the samples, respectively. Five cases of dual infection
      between P8 and P4 genotypes occurred, indicating the potential for reassortment
      between members of different rotavirus genogroups. The P9 genotype could not be
      confirmed in 3 cases (1.9%), while the P10 genotype was not observed at all,
      indicating the scarcity or absence of these VP4 genotypes in this region.
      Interestingly, we identified the newly-described P12 VP4 genotype in 6 cases
      (3.8%), suggesting a wide geographical distribution. Furthermore, several samples
      with sufficient RNA by gel electrophoresis remained untyped by the probes used in
      this study, and may represent putative "new" human VP4 genotype(s).

PMID- 8551251
TI  - HTLV infection among Italian intravenous drug users and North African subjects
      detected by the polymerase chain reaction and serological methods.
AB  - Six hundred intravenous drug users (IVDUs) and two hundred North Africans were
      screened for human T-cell leukemia virus (HTLV) antibodies using several
      serological methods. Eighteen of the eighty-two HTLV-seropositive individuals
      were also tested by the polymerase chain reaction-DNA enzyme immunoassay (PCR
      DEIA), a non-isotopic method of immunoenzymatic detection of the amplified DNA.
      Of these eighteen subjects, eight IVDUs were found to be HTLV-II-positive by the
      PCR-DEIA, whereas all of the eighteen subjects were negative for HTLV-I. Western
      blot (WB) confirmed six of the eight HTLV-positive subjects, while the results of
      the remaining two were indeterminate. The results confirmed the PCR-DEIA as a
      rapid and an efficient method of discriminating between HTLV-I and HTLV-II
      infection, whereas serological tests, including the WB, have limitations in terms
      of specificity and sensitivity. Moreover, this study showed a higher frequency of
      HTLV seroreactivity in the Italian IVDU population than in previous studies and
      confirmed that HTLV-II is more frequent than HTLV-I in this population.

PMID- 8551252
TI  - Human herpesvirus-6: a survey of presence and distribution of genomic sequences
      in normal brain and neuroglial tumors.
AB  - In an attempt to study the frequency and distribution of human herpesvirus-6 (HHV
      6) infection both in normal and neoplastic brain tissues in vivo, polymerase
      chain reaction was used to look for HHV-6 genomes: 1) in samples, obtained at
      necropsy, from different regions of the brain of immunocompetent adult subjects
      and of patients who died of AIDS; 2) in the surgical biopsies of a well
      characterized series of primary brain tumors of neuroglial origin. HHV-6-specific
      sequences were identified in six of nine brain samples from immunocompetent
      subjects, and in four of seven brain samples from AIDS patients. Viral sequences
      were identified in the specimens derived either from the grey (frontal cortex and
      basal ganglia) or from the periventricular white matter. HHV-6 DNA was found only
      in 6 of the 37 primary brain tumor biopsies examined. This study provides for the
      first time molecular evidence of a wide distribution of HHV-6 infection in the
      brain tissues of a high proportion of subjects, both in normal and in impaired
      immunity. In this large series of tumor biopsies the presence of HHV-6 genomic
      sequences is a rare phenomenon, arguing against a major role of this herpesvirus
      in the pathogenesis of primary brain tumors of neuroglial origin in
      immunocompetent subjects.

PMID- 8551253
TI  - Hepatitis C virus RNA in peripheral blood mononuclear cells: relation with
      response to interferon treatment.
AB  - The polymerase chain reaction (PCR) was used to investigate the presence of
      positive and negative hepatitis C virus (HCV) RNA strands in serum and peripheral
      blood mononuclear cells (PBMC) of 20 patients with histologically proven HCV
      related chronic liver disease. All patients completed a course of interferon
      (IFN) treatment (6 MU of IFN-alpha 2b three times a week for 24 weeks) and were
      followed-up for 12 months after treatment was discontinued. Pre-treatment, end
      treatment and 6-month follow-up serum and PBMC samples were examined. At
      enrollment, the positive strand of HCV-RNA was detected in serum of 18 patients
      (90%), the negative strand in none. Positive-stranded HCV-RNA was detected in
      PBMC of 15 patients (75%), 13 of whom also had detectable levels of negative
      stranded HCV-RNA in PBMC. By the end of the treatment, 12 patients (60%) were
      responders. The pre-treatment HCV infection of PBMC, indicated by the presence of
      both RNA strands, was found in 8 (66.7%) responders compared to 5 (62.5%) non
      responders (P = n.s.). End-treatment loss of PBMC HCV-RNA correlated
      significantly with the response since it occurred in all responders compared to 2
      non-responders (P = 0.02). However, end-treatment-negative serum and PBMC HCV-RNA
      did not predict the occurrence of a sustained response, which was observed at
      month 12 in 5 of 12 responders (P = n.s.). On the other hand, the persistent
      absence of HCV RNA in serum and PBMC at the end of the 6-month follow-up was
      significantly associated with the occurrence of a sustained response (P <
      0.0001).

PMID- 8551254
TI  - Use of the polymerase chain reaction to detect genomes of human immunodeficiency
      virus and cytomegalovirus in post-mortem tissues.
AB  - The polymerase chain reaction (PCR) was used to amplify a 149 base-pair region of
      the cytomegalovirus (CMV) genome and a 551 base-pair region of the HIV-1 proviral
      long terminal repeat (LTR) present in DNA extracted from post-mortem tissue.
      Multiple tissues (n = 116) obtained from 16 patients which were subjected to PCR
      were also subjected to cell culture and histopathological analyses. One hundred
      and seven samples (92%) contained CMV DNA and 66/116 (57%) contained HIV proviral
      DNA at a level of > or = 10 genomes. Both viruses were detected in 60/116 (51.7%)
      of samples, with co-infection most frequent in the lung (69%). Cell culture for
      CMV detected 9.3% of the PCR-positive samples, whilst histology identified CMV
      inclusions in 15.9% of samples, all of which were CMV PCR-positive. CMV was most
      frequently detected in adrenal and lung tissues by histology. These results show
      that co-infection with CMV and HIV is a common occurrence in organs from AIDS
      patients and provide further evidence for a role of cytomegalovirus in the
      pathogenesis of AIDS.

PMID- 8551255
TI  - Comparison of two immunoassay procedures for detecting enterovirus IgM.
AB  - Enteroviruses cause significant illness in man but viral diagnosis is
      problematic. Enterovirus-specific IgM tests have been developed but due to the
      difficulties of obtaining reliable control sera the interpretation of assay data
      remains mainly arbitrary and empirical. The present study was undertaken to
      assess the reliability of such assays by comparing two tests performed
      independently in two different laboratories: a mu-capture radioimmunoassay
      (MACRIA) which utilizes 35S-labelled Coxsackie virus antigens and an enzyme
      immunoassay (EIA). A feature of the MACRIA was that sera were tested in one large
      batch whereas the EIA was in routine use in a reference laboratory. The MACRIA
      was easy to perform but more suitable for research investigations than routine
      diagnostic use. Similar results were detected in the majority of sera tested in
      the two assays with 85% concordance achieved on testing 120 sera. Of the 18
      discrepant results, 11 were positive by EIA only and 7 by MACRIA only. 89-95%
      concordance was obtained on testing sera against individual Coxsackie B1-5
      serotypes, moreover 52% of the sera positive in MACRIA were reactive against only
      one viral antigen and the results on certain of the more strongly reactive sera
      suggested the existence of a measure of type specificity in the MACRIA test.
      Qualitative differences between the two tests highlighted problems of
      interpretation in the absence of a gold standard and cautioned against sole
      reliance on serology for diagnosis of enteroviral infections.

PMID- 8551256
TI  - Rapid genotyping of hepatitis C virus RNA-isolates obtained from patients
      residing in western Europe.
AB  - Two rapid genotyping methods for hepatitis C virus (HCV), the line probe assay
      (Inno-LiPA) and the subtype-specific core amplification system [Okamoto et al.,
      (1992b) Journal of General Virology 73:673-679], were applied to 58 HCV isolates
      which were typed as type 1 (n = 37) and type 2 (n = 21) by sequence analysis of
      the 5' untranslated region (5'UTR). The line probe assay targets the 5'UTR and
      recognized 12 subtype 1a, 25 subtype 1b, 18 subtype 2a, 2 subtype 2b and 1
      subtype 2d in accordance with sequence analysis of this region. Subtype-specific
      core amplification revealed 7 discrepancies among the 37 type 1 isolates when
      compared to LiPA. A different subtype was observed in 3 isolates (1a versus 1b),
      2 isolates remained untyped and 2 isolates showed a coinfection of subtype 1a and
      1b. The first 5 discrepancies were confirmed by sequence analysis of the core
      region whereas the coinfection could not be confirmed. Of the 21 type 2 isolates
      only one could be typed by subtype-specific core amplification. HCV RNA was
      detected in all 21 cases after the general first round of polymerase chain
      reaction (PCR). Direct sequencing of the core region indicated sequence variation
      as a source of failure. It is concluded that LiPA results are conclusive for
      typing of HCV. However, LiPA is hampered occasionally for subtyping by lack of
      subtype-specific sequence variation in 5'UTR. Subtyping results by subtype
      specific core amplification were accurate. However, it seems that this assay is
      not suitable for the identification of genotype 2 isolates that circulate in
      patients living in Western Europe.

PMID- 8551257
TI  - Rapid and sensitive streptavidin-biotin amplified fluorogenic enzyme-linked
      immunosorbent-assay for direct detection and identification of dengue viral
      antigens in serum.
AB  - Each of the four serotypes of dengue viruses is responsible for a spectrum of
      illnesses that range from nonspecific febrile syndrome with good prognosis to
      dengue haemorrhagic fever or dengue shock syndrome. Definite diagnosis of dengue
      is provided by the detection of virus in acute-phase sera of patients. Virus
      isolation can be accomplished with mosquito cell lines or mosquito inoculations.
      However, these methods are time consuming and labour intensive. The reverse
      transcriptase polymerase chain reaction (RT-PCR) provides a potential means of
      rapid diagnosis but requires specialised facilities and equipment and is
      expensive. Therefore a rapid, simple, sensitive, and economical method for direct
      detection of viral antigens in viraemic sera is needed for clinical and
      epidemiological investigations. An amplified fluorogenic enzyme-linked
      immunosorbent assay (F-ELISA) is described for the detection and identification
      of dengue-3 viruses in serum specimens. This assay utilizes biotinylated mouse
      IgG antibody directed against dengue antigens captured by anti-dengue monoclonal
      antibody coated onto polystyrene microplate wells. It takes advantage of the high
      affinity of biotin for the multivalent binding sites of streptavidin-labelled
      beta-galactosidase, and combines the amplification effect of biotin-streptavidin
      interaction with the high sensitivity of fluorogenic detection methods. Following
      optimisation of the procedure by reducing non-specific binding of proteins and
      enhancing the specific binding of antigens, F-ELISA was tested on 259 sera
      submitted routinely to our laboratory for confirmation of dengue diagnosis. The
      sensitivity of the F-ELISA was 90%, the specificity was 99% and the agreement
      rate was 98% between F-ELISA and virus isolation results.

PMID- 8551258
TI  - Guinea pig and human cytomegaloviruses do not share cross-reactive neutralizing
      epitopes.
AB  - Human (HCMV) and guinea pig (gpCMV) cytomegaloviruses share biological
      similarities and DNA sequence homologies. Therefore, human and guinea pig sera
      were tested for cross-reactive antibodies. In eight human sere (four HCMV
      seropositive and four HCMV-seronegative), low levels of neutralizing activity
      against gpCMV were not associated with antibodies to HCMV. The convalescent sera
      of one of three humans infected with either HCMV Towne vaccine or wild-type HCMV
      developed a fourfold increase in neutralizing titers to gpCMV after infection,
      but none of seven guinea pigs immunized with either HCMV Towne or purified HCMV
      gB developed neutralizing activity against gpCMV. Guinea pigs immunized with
      gpCMV did not develop antibodies to HCMV or human gB. Neither gpCMV, HCMV Towne
      stain or purified HCMV gB induced cross-reactive antibodies against the
      heterologous virus as detected by enzyme immunoassay. Our results indicate that
      gpCMV and HCMV share a very limited number, if any, of cross-reactive
      neutralizing epitopes.

PMID- 8551259
TI  - Antibody prevalence and immunoglobulin IgG subclass pattern to Norwalk virus in
      Sweden.
AB  - The antibody prevalence in Sweden to Norwalk virus (NV) was investigated using a
      baculovirus expressed capsid antigen. One hundred thirty-two serum samples were
      examined for IgA, total IgG and IgG subclass antibodies to Norwalk virus. In
      young children, NV IgG antibody prevalence was higher than the IgA prevalence,
      whereas no difference was found in individuals older than 21 years. The IgG
      antibody prevalence was 50% in children below 5 years of age and increased to >
      80% in individuals older than 10 years of age. To examine the IgG antibody
      response in more detail, IgG subclass patterns were characterized. IgG 1
      predominated in all age groups. IgG 4, usually detected after repeated exposure
      to antigen, was the second most prevalent subclass, but was only found in
      individuals older than 21 years of age. IgG 3 subclass antibodies were found in
      13% and IgG 2 in 3% of the sera examined. IgG 3 subclass antibodies have been
      recognized as a marker for recent or ongoing viral infections.

PMID- 8551260
TI  - Hepatitis C virus infection of mononuclear cells from peripheral blood and liver
      infiltrates in chronically infected patients.
AB  - The mechanisms underlying chronicity of hepatitis C virus (HCV) infection are
      poorly understood, but the importance of impaired viral clearance by the immune
      system has been suggested. The prevalence of HCV infection of peripheral blood
      mononuclear cells (PBMC) was in investigated in 34 persistently infected patients
      with anti-HCV (7 with liver cirrhosis, 10 with chronic active hepatitis, 5 with
      chronic persistent hepatitis, 4 with chronic lobular hepatitis, and 8 healthy
      carriers) by polymerase chain reaction (PCR). HCV infection of 116 T cell clones
      derived from liver infiltrating mononuclear cells obtained from 3 patients with
      chronic liver disease was examined using the same methods. HCV genomic sequences
      were found in fresh, unstimulated PBMC from 20 patients with cirrhosis, and
      chronic active and persistent hepatitis, but in none of the healthy carriers and
      only in mitogen-activated cells from 1 out of 4 patients with autoresolving
      chronic lobular hepatitis. Active PBMC infection was confirmed by identification
      of anti-genomic HCV sequences in the majority of HCV RNA-positive cells (fresh or
      mitogen-stimulated). A high percentage of T cell clones obtained from liver
      infiltrates were found to be infected by HCV. These findings suggest that HCV
      infection of lymphatic cells plays a role in the pathogenesis of chronically
      evolving liver damage. PBMC may represent a reservoir for latent infection and a
      site for viral multiplication.

PMID- 8551261
TI  - Serial quantitation of HPV-16 in the smears of women with mild and moderate
      dyskaryosis.
AB  - The aim of this study was to examine the efficacy of semi-quantitative polymerase
      chain reaction (PCR) testing in cervical smears as an adjunct to cytological
      surveillance in a cohort of women with mild or moderate dyskaryosis. The study
      population comprised a group of 62 women who underwent twelve months of
      cytological and colposcopic surveillance as part of a larger randomised
      prospective study of women with mild and moderate dyskaryosis. Semi-quantitative
      PCR for HPV-16 DNA was carried out on the initial and twelve month study smears
      before a large loop excision of the transformation zone (LLETZ) was carried out.
      Smears from a control population which comprised 167 women without a history of
      abnormal cervical cytology who were attending family planning and general
      practitioner clinics for routine cervical smears were tested similarly. The
      presence of high or intermediate levels of HPV-16 DNA on both the initial and
      twelve month study smear was positively associated with the identification of
      cervical intraepithelial neoplasia (CIN) grades II or III in the LLETZ specimen
      (P = 0.01). While the combination of HPV-16 DNA testing with cytology on a repeat
      cervical smear improved the selection of women with underlying CIN II/III, there
      was still a false negative rate of 53%. Twenty-nine women had 'low risk' levels
      of HPV-16 DNA and mild dyskaryosis or less on both repeat smears indicating
      suitability for surveillance, but in fact 34% of them had CIN II/III. This study
      supports the finding reported previously of an association between high and
      intermediate levels of HPV-16 DNA and CIN II/III.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8551262
TI  - Human herpesvirus type 7 in blood donors: detection by the polymerase chain
      reaction.
AB  - In order to evaluate the prevalence of human herpesvirus type 7 (HHV-7) in adult
      blood donors oral lavage fluid, buffy coat, and urine samples from 112 persons
      were examined by the polymerase chain reaction (PCR) at one time point. In
      addition, 11 donors were studied longitudinally over 11 weeks. When the results
      of the initial and the longitudinal study were combined HHV-7 DNA was found in
      samples from 109 of 112 (97.3%) adult blood donors. On the basis of different
      sensitivity levels of the first and the nested PCR differences were detected in
      the viral DNA load in the samples. It was found that lavage fluid regularly
      carried significantly higher DNA concentrations than buffy coat. Out of 112
      donors, 102 (91.1%) and 8 (7.1%) were positive in the first, less sensitive PCR
      in lavage fluid and buffy coat, respectively (P < .0001). After nested PCR, 107
      (95.5%) and 74 (66.1%) were positive in lavage fluid and buffy coat, respectively
      (P < .0001). Urine samples were found positive only sporadically. The
      longitudinal study showed that the oral lavage fluid of most of the donors
      consistently carried HHV-7 over up to 53 weeks, whereas buffy coat samples were
      positive less often. In conclusion, HHV-7 is found frequently in adult blood
      donors in the oral lavage fluid and buffy coat, which are, therefore, potential
      sources of HHV-7 transmission.

PMID- 8551263
TI  - Quantitation of human cytomegalovirus genomes in the brain of AIDS patients.
AB  - Human cytomegalovirus (HCMV) is one of the major pathogens causing neurologic
      disease in the immunocompromised host. A competitive nested polymerase chain
      reaction (PCR) was used to determine DNA load, distribution, and sequence
      variability of HCMV genomes in the brain of AIDS patients with and without HCMV
      encephalitis confirmed by histology and immunocytochemistry. By quantitative PCR,
      HCMV genomes were found to be distributed diffusely in the central nervous system
      (CNS) of all five patients with histologically proven HCMV encephalitis, but also
      in the brain of five of eight AIDS patients without neuropathological evidence of
      HCMV encephalitis. The viral DNA load in cases with HCMV encephalitis was
      increased 10- to 1,000-fold as compared to patients without evidence of
      encephalitis. A viral load above 6,000 copies HCMV/10(6) copies beta-globin was
      found to be highly suggestive for HCMV encephalitis. Characterization of PCR
      products by temperature gradient gel electrophoresis (TGGE) and direct sequencing
      allowed us to detect a sequence variability of the amplified fragment of HCMV
      glycoprotein B (gB) among different patients, but also among different HCMV foci
      within the same patient. Furthermore, two of five AIDS patients with HCMV
      encephalitis most likely experienced double infections with different HCMV
      strains. The experimental procedure described in this study should also be
      applicable to the detection of significant HCMV DNA levels in biopsy samples.

PMID- 8551264
TI  - Seroepidemiology of Inoue-Melnick virus in the general population of Buffalo, New
      York.
AB  - The prevalence of antibodies to Inoue-Melnick virus (IMV) types 1 and 2 in the
      general population of Buffalo, New York, was studied. Serum specimens were
      collected from blood donors, and pediatric sera were provided from the Buffalo
      Children's Hospital. Neutralizing antibody titers against IMV were measured with
      established procedures. Very high prevalence of antibodies to both IMV types 1
      and 2 were found in sera from children of Buffalo, especially in the age group 15
      19 years (nearly 100%). The antibody positivity gradually decreased with
      advancing age, except for the groups of age 60 and older. This is in sharp
      contrast to a previous report examining sera from the people of Osaka, Japan, in
      which IMV antibody was not found in children under 10 years of age. In the group
      of teenagers in Buffalo, with high geometric mean antibody titers, an association
      with any disease was not found. The peculiar distribution of antibodies to IMV
      was considered to be possibly related to the high incidence of multiple sclerosis
      (MS) in the Buffalo area, in contrast to the data from Osaka, Japan, which is a
      low incidence area for MS.

PMID- 8551265
TI  - Serum anti-p24 antibody concentration has a predictive value on the decrease of
      CD4 lymphocyte count higher than acid-dissociated p24 antigen.
AB  - We studied the prognostic value on the decrease of CD4 lymphocyte count of anti
      p24 antibody (ab) titer and compared this value with that of polyclonal and
      monoclonal p24 (ag) titer before and after immune complex dissociation (ICD); 53
      human immunodeficiency virus (HIV)-infected patients having CD4+ counts above
      400/mm3 when first examined were followed up over a 3-year period including at
      least four visits; HIV disease progressors (n = 18) were defined as having CD4+
      counts below 200/mm3 and non-progressors (n = 35) as having CD4+ counts still
      above 400/mm3 at the end of follow-up. Sera were collected at each visit and
      assayed for p24 ag with and without ICD and for anti-p24 ab titer. The mean anti
      p24 ab titer of progressors and of non-progressors at entry was significantly
      different. A threshold of anti-p24 ab titer indicating a HIV progression was
      determined at 1/300. The proportion of individuals with an anti-p24 ab titer
      lower than 1/300 at least once during the study period was 34% in non-progressors
      and 94% in progressors. The difference between progressors and non-progressors at
      entry was significant with monoclonal p24 ag without ICD and more significant
      with monoclonal p24 ag after ICD. The marker having the highest predictive value
      was the anti-p24 ab titer, then monoclonal p24 ag with ICD, then polyclonal p24
      ag with ICD. Anti-p24 ab is an earlier and stronger marker of the decrease of CD4
      lymphocyte count than p24 ag even after ICD.

PMID- 8551266
TI  - Comparison of human immunodeficiency virus biological phenotypes isolated from
      cerebrospinal fluid and peripheral blood.
AB  - Quantitative human immunodeficiency virus (HIV) cultures were carried out on
      cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs), and plasma
      from patients with HIV in order to compare the infectious HIV load. The HIV
      strains isolated were studied for syncytium-inducing (SI) capacity, using the MT
      2 cell line, in order to compare the HIV strain phenotype of blood and CSF
      isolates. Forty-two patients with HIV-1 infection were enrolled in the study, 33
      of whom had neurological symptoms and 9 of whom were without neurological
      symptoms. HIV was isolated from 16 (38%) of the 42 CSF cultures, with a low mean
      titer of 6.3 +/- 3.4 tissue-culture-infective doses (TCID) per milliliter.
      Patients with HIV-positive CSF culture had a viral load in PBMCs of 40.5 +/- 15.5
      TCID per 10(6) PBMC and in plasma of 104.7 +/- 9.3 per milliliter. Two (15%) of
      the 13 CSF isolates were SI strains, compared to 17 (56.6%) of the 30 PBMC
      isolates and 13 (54%) of the 24 plasma isolates (P < 0.05). Five of the nine
      patients from whom CSF and blood strains were obtained had the same viral
      biological phenotype. This study suggests that different HIV variants may be
      found in different body fluids and/or cells.

PMID- 8551267
TI  - Genomic characterization of hepatitis C virus isolates from Argentina.
AB  - Thirty-three Argentinian patients infected with hepatitis C virus (HCV) were
      studied for viral genotyping. The patients included 10 hemophiliac and 4
      polytransfused children and 19 adults: 3 polytransfused, 7 dialyzed and 9
      sporadic cases. Core-based genotyping permitted the classification of 31 samples.
      Genotypes II, I and V were the most frequent: 21 (63.6%), 16 (48.4%) and 10
      (30.3%) of the 33 patients, respectively. Only one polytransfused patient carried
      genotype IV. Genotype II was detected in 7 out of 9 sporadic cases. Thirteen
      patients (39.3%) were coinfected with two genotypes, and 2 others were coinfected
      with three genotypes. The remaining 2 samples which could not be typed were
      characterized following the restriction fragment length polymorphism (RFLP)
      method, and were classified as type 1. One of these had two consecutive
      transitional mutations in the 5' untranslated region (5' UTR).

PMID- 8551268
TI  - Deletion in the L1 open reading frame of human papillomavirus type 6a genomes
      associated with recurrent laryngeal papilloma.
AB  - Human papillomavirus (HPV) type 6a genomes with a large deletion in their L1 open
      reading frames (ORF) were found in two of five recurrent cases of laryngeal
      papilloma. One of these mutant HPVs had a 186 base pair (bp) deletion near the N
      terminus end of the L1 ORF, which encodes a major capsid protein. The other had a
      454 bp deletion at the C-terminus end of L1 at which is located a nuclear
      localising signal (NLS). No other large deletion or insertion was found in the
      remaining regions of all five HPV6a genomes. The laryngeal papillomas which
      harboured the mutant viruses showed typical hyperplasia and pathological changes
      as observed in tumours induced by the wild-type virus. The biological
      significance of the two large deletions in the late region of HPV6a associated
      with laryngeal papilloma is discussed.

PMID- 8551269
TI  - Large-scale study suggests no direct link between human herpesvirus-6 and primary
      Sjogren's syndrome.
AB  - The aim of this study was to evaluate the role of human herpesvirus-6 (HHV-6) in
      the development of primary Sjogren's syndrome (PSS). Serum HHV-6 antibody levels,
      as measured by immunofluorescence assay (IFA) and the prevalence of HHV-6 DNA in
      peripheral blood mononuclear cells (PBMCs) determined by polymerase chain
      reaction (PCR), were studied in 49 PSS patients and 50 control subjects, all in
      patients in the University Hospital Internal Medicine ward, Limoges, France. In
      addition, portions of labial salivary gland were obtained from 34 patients and 15
      controls, the presence of viral DNA being detected by the same PCR technique. The
      results were then compared with clinical observations of systemic disease
      manifestations in patients and a histological study of salivary gland
      involvement. No significant difference in HHV-6 seroprevalence was found between
      control subjects (50.0%) and patients (63.3%) nor was there any statistically
      significant difference between patient and control groups for total viral DNA in
      PBMCs (22.4%, 12.0%) and salivary glands (8.8%, 6.6%). Analysis of clinical and
      histological data revealed no detectable correlation between disease severity and
      viral involvement. Tests for HHV-6A and HHV-6B proved positive in patient and
      control groups, HHV-6B being the most frequently encountered type in both groups.
      In conclusion, the results of this large-scale trial does not confirm the
      suspected direct role of HHV-6 in the etiology of PSS.

PMID- 8551270
TI  - Probable implication of mutations of the X open reading frame in the onset of
      fulminant hepatitis B.
AB  - A pathogenic role of precore-defective mutation in the onset of fulminant
      hepatitis B has been suggested. However, precore-defective mutants do not always
      cause fulminant hepatitis B and are not always isolated from affected patients.
      These findings strongly suggest the presence of some additional important
      mutations outside the precore region in fulminant hepatitis. In the present
      investigation an attempt was made to sequence the X open reading frame of
      hepatitis B virus DNA isolated from seven patients with fulminant hepatitis B and
      five patients with acute hepatitis B. The latter were used as controls. Since the
      X open reading frame encodes the X protein and contains the core
      promoter/enhancer II complex, some critical mutations may enhance or disrupt the
      replication and expression of hepatitis B virus DNA leading to fulminant
      hepatitis. A C-to-T substitution was found at nucleotide (nt) 1655, an A-to-T
      substitution at nt 1764 and a G-to-A substitution at nt 1766 in 4, 5 and 5
      patients, respectively, out of the seven with fulminant hepatitis. These
      substitutions were not recognized in the patients with acute hepatitis. These
      mutations might change the function of the X protein and core promoter/enhancer
      II complex. It is suggested, therefore, that these mutations, as well as the
      precore-defective mutation, may play an important role in the pathogenesis of
      fulminant hepatitis.

PMID- 8551271
TI  - Perinatal infection and persistence of human papillomavirus types 16 and 18 in
      infants.
AB  - Perinatal transmission of genital human papillomaviruses (HPVs), including HPV-16
      and -18 which are associated with anogenital carcinomas have been described
      previously [Pakarian et al. (1994): British Journal of Obstetrics and Gynaecology
      101:514-517; Kaye et al. (1994) Journal of Medical Virology 44:415-421]. A study
      was undertaken to investigate whether HPV-16 and -18 DNA in infants contaminated
      at delivery persists until they are 6 months of age. Of 61 pregnant women
      recruited, 42 (68.8%) were HPV-16 and 13 (21.3%) were HPV-18 DNA positive. At 24
      hr there were transmission rates from HPV DNA positive mothers to their infants
      of about 73% (HPV-16: 69%; HPV-18: 76.9%). Ten mothers who were both HPV-16 and 
      18 DNA positive produced six (60%) infants who were also doubly positive at 24
      hr. HPV DNA persisted to 6 weeks in 79.5% (HPV-16: 84%; HPV-18: 75%) of those
      infants who were positive at birth. At 6 months of age, persistent HPV-16 DNA was
      detected in 83.3% of cases, but HPV-18 DNA persistence at this time was 20%. To
      extend these observations over a greater age range of children HPV-16 L1 and L2
      proteins were expressed in insect cells via recombinant baculoviruses and sera
      from 229 children were examined to determine at what age IgM antibodies to HPV
      were acquired. There was a bimodal distribution of IgM seropositivity which
      peaked between 2 and 5 and 13 and 16 years of age, suggesting that two distinct
      modes of transmission may occur. The observation that infection with high cancer
      risk genital HPVs may occur in early life and persist is of considerable
      importance for HPV vaccine strategies.

PMID- 8551272
TI  - PCR detection of JC virus DNA in brain tissue from patients with and without
      progressive multifocal leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of
      the central nervous system, which is thought to be a result of the reactivation
      of JC virus (JCV), a human polyomavirus. The disease occurs in individuals with
      immunosuppression and in recent years there has been an increase in PML cases due
      to AIDS. A nested polymerase chain reaction (n-PCR) was employed to detect JCV
      and BK virus (BKV) DNA in brain tissue collected postmortem from 28 AIDS patients
      with PML and from 13 patients without PML, but with other diagnoses, including
      solid tumors, Alzheimer's disease, thromboembolism, myocardial infarction and
      acute cerebrovascular diseases. All 28 brain specimens from the patients with PML
      were positive for JCV DNA when tested by n-PCR and three of the latter were also
      positive for BKV DNA. These results were confirmed by an enzyme restriction
      analysis and a DNA hybridization assay. Interestingly, in this study, JCV DNA was
      also found in 6 brain tissue specimens from 4 subjects with diseases unrelated to
      PML or AIDS. All the brain specimens from the control group were negative for BKV
      DNA. The results confirm that the n-PCR is a useful tool for PML diagnosis. The
      presence of JCV DNA in the brain tissue of patients without PML is particularly
      important since it indicates that JCV could be latent in the brains of
      immunocompetent individuals. Moreover, detection of simultaneous presence of JCV
      and BKV in the brain tissue of the patients with PML demonstrates that BKV may
      also infect the human brain without causing any apparent neurological disease.

PMID- 8551273
TI  - Quantitation of anti-hepatitic C virus antibodies in interferon-treated patients
      by S29-1/S4 ELISA.
AB  - In 23 patients with chronic hepatitis C who have undergone interferon (IFN)
      treatment, quantitation of anti-hepatitis C virus IgG antibodies by a second
      generation assay S29-1/S4 ELISA [Sato et al. (1993): Microbiology and Immunology
      37: 295-304]. (anti-S29-1/S4) was compared with that of anti-HCV core IgG
      antibodies (C22-3, anticore) and the presence of viral RNA confirmed by the
      reverse transcription-nested polymerase chain reaction (RT-nested PCR). In 12
      complete responders with loss of HCV-RNA and normal alanine aminotransferase
      (ALT) levels at 6 months after therapy, IgG antibodies quantified by a second
      generation assay have decreased significantly at the end of treatment (P < 0.05).
      Further significant reduction of anti-S29-1/S4 titers was observed at 6 months
      after therapy (P < 0.01) as well as anti-core antibodies (P < 0.01). On the other
      hand, in 11 non-responders with persistent or intermittent viremia at 6 months
      after therapy, no significant change in the level of anti-S29-1/S4 titers was
      observed, whereas anti-core titers have decreased at the end of therapy (P <
      0.01). In contrast, both levels of anti-S29-1/S4 and anti-core have increased at
      6 months after treatment (P < 0.05). It is concluded that, although it appears
      difficult to monitor the effect of virus clearance during IFN therapy, changes in
      anti-S29-1/S4 titers after IFN treatment correlate with virus clearance and with
      anti-core titers.

PMID- 8551274
TI  - Hepatitis C virus infection in an HIV-positive population in Normandy:
      antibodies, HCV RNA and genotype prevalence.
AB  - The prevalence and the characteristics of hepatitis C virus infection (HCV) in
      161 HIV-positive patients were studied. HCV seroprevalence was determined by
      enzyme immunoassay and recombinant immunoblot assay (RIBA). Two different reverse
      transcriptase polymerase chain reaction (RT-PCR) methods were also used to test
      the HCV-seropositive samples and 50 EIA-negative sera used as controls. The RNA
      HCV-positive sera were genotyped by the LiPA procedure. Associations of HCV
      status with demographic characteristics and risk factors were assessed by chi 2
      and Fisher's exact tests. The seroprevalence of HCV was 34.2% with a significant
      difference between blood and sexual exposure risk groups (60.6% vs. 13.6%,
      respectively; P < 0.0001). Thirty-six of the 55 anti-HCV-positive sera were also
      positive for HCV RNA, and PCR detected HCV RNA in 8 HCV-seronegative patients.
      Various RIBA profiles were found and all sera were positive for antibodies to the
      c33 protein. A proportion of sera had elevated levels of transaminase activity
      (37.2%), and abnormal liver function as associated with HCV infection. Forty-two
      samples were genotyped and five genotypes and subtypes of the HCV virus were
      detected. Genotype 1a was the most frequent in this cohort, although genotype 1b
      is generally more common in France. The majority (94.1%) of the patients with
      genotype 1a had a history of blood exposure, which may account for the
      difference.

PMID- 8551275
TI  - Double resistance to ganciclovir and foscarnet of four human cytomegalovirus
      strains recovered from AIDS patients.
AB  - Four human cytomegalovirus (HCMV) isolates from four different AIDS patients
      treated with both ganciclovir and foscarnet and not responding clinically to
      antiviral treatment, were studied in order to verify the occurrence of double
      resistance to both drugs, and to define whether single or multiple HCMV strains
      could be responsible for the double resistance. Peripheral blood leukocytes
      (PBL), the relevant conventional viral isolates, and plaque-purified strains from
      all four patients were examined by antiviral drug susceptibility testing by an
      immediate-early antigen plaque reduction assay and by restriction fragment length
      polymorphism (RFLP) analysis using polymerase chain reaction (PCR)-amplified
      multiple genome regions and endonucleases. All four HCMV strains had a high level
      of resistance to both ganciclovir and foscarnet. A single HCMV strain was shown
      to be responsible for the dual resistance in each patient. HCMV strain identity
      and uniqueness were shown for each of the four patients in blood samples, viral
      isolates, and plaque-purified strains. In addition, in two patients the same
      single HCMV strain shifted progressively from drug sensitivity to ganciclovir and
      then to ganciclovir-foscarnet resistance. These findings document that resistance
      to both ganciclovir and foscarnet of HCMV strains recovered from blood of AIDS
      patients represents an emerging problem. Although it is known that multiple HCMV
      strains may cocirculate in the blood of AIDS patients, single strains appear to
      be responsible for the dual resistance. Molecular mechanisms responsible for the
      double resistance of the four reported strains are under study.

PMID- 8551276
TI  - Quantitative measurement of HBeAg in chronic hepatitis B: a comparison between a
      radioimmunoassay, a fluorescence ELISA and a chemiluminescence ELISA.
AB  - The presence of the hepatitis B e antigen (HBeAg) in peripheral blood of chronic
      hepatitis B patients is a widely accepted marker of active replication of the
      hepatitis B virus. HBeAg determination during interferon therapy is a useful
      guide for the therapeutic regimen. The aim of the study was to compare the
      suitability of an HBeAg radioimmunoassay (RIA, Abbott Laboratories, North
      Chicago, IL, USA), the IMx-HBeAg assay (IMx, Abbott Laboratories) and the
      HBeAg/anti-HBe Amerlite assay (Amerlite, Johnson & Johnson Clinical Diagnostics,
      Cardiff, UK) for semiquantitative monitoring of HBeAg during therapy. HBeAg
      levels in serum samples obtained before and during interferon therapy were
      measured using an in-house standard calibrated against the Paul Ehrlich Institute
      HBeAg reference preparation (PEI standard). When serial dilutions of pretreatment
      serum samples were assayed by the three methods, radioimmunoassay was found to be
      highly sensitive although it had a very limited working range (0.5 to 12 PEI
      U/ml). A broader linear working range was observed for Amerlite (0.5 to 50 PEI
      U/ml) and the IMx assay (0.5 to 100 PEI U/ml). The intra-assay and interassay
      variations did not differ significantly. Since the IMx assay was less susceptible
      to sample variation and had a broad working range, semiquantitative measurement
      of HBeAg in one diluted and one undiluted sample by this assay may justifiably be
      introduced as routine procedure. Routine semiquantitative HBeAg measurement may
      improve individual dose adjustments and thus the success of interferon therapy.

PMID- 8551278
TI  - Pathogenesis of hepatitis A in orally inoculated owl monkeys (Aotus trivirgatus).
AB  - The pathogenesis of hepatitis A virus (HAV) infection was studied in owl monkeys
      following oral administration of the wild-type HM-175 strain of HAV. Stools were
      collected daily and blood and pharyngeal swabs twice weekly for viral isolation,
      and animals were necropsied at various intervals after inoculation. Organs were
      examined for the presence of virus by isolation in cell culture and for viral
      antigens by immunofluorescence. Monkeys excreted HAV in the stools for 1-4 days
      after inoculation, presumably due to the residual unabsorbed inoculum. No virus
      was found in stools for the next 2-3 days. HAV re-appeared on days 4-7 and then
      persisted through day 39. Viremia occurred on the 10th day and continued until
      day 35. Virus was isolated occasionally from throat swabs 1 or 2 weeks after it
      was detected in stools and blood, and there was no evidence that HAV replicated
      in the pharyngeal tissues. Animals acquired anti-HAV antibody by the 4th week,
      and alanine aminotransferase (ALT) was elevated 5-5.5 weeks after inoculation.
      HAV was isolated from liver 5 days after inoculation; however, viral antigens
      were first detected in Kupffer cells of the liver at 14 days and in hepatocytes
      at 21 days. HAV antigen was detected in epithelial cells of the intestinal crypts
      and in the cells of the lamina propria of the small intestine 3 days
      postinoculation and thereafter until the 5th week, suggesting that these cells
      might represent an additional site of HAV replication.

PMID- 8551277
TI  - Experimental myocarditis induced by two different coxsackievirus B3 variants:
      aspects of pathogenesis and comparison of diagnostic methods.
AB  - The ability of two coxsackievirus B3 (CBV3) variants to induce myocarditis in
      BALB/c mice was studied and plaque-forming assay, polymerase chain reaction
      (PCR), in situ hybridization, and immunohistochemistry were compared for
      detecting viruses and viral components in the myocardium. The virological
      findings were related to histopathologic and ultrastructural changes in the
      myocardium. CBV3-W induced severe myocarditis characterized by massive myocyte
      necrosis. Widely distributed myocyte damage clearly preceded modest inflammatory
      infiltrates in the myocardium. In contrast, CBV3-M1 induced mild myocardial
      injury. Both variants caused fulminant pancreatitis with nearly complete necrosis
      of the exocrine pancreas. CBV3 RNA was identified by PCR in the myocardium of
      CBV3-W-infected mice until the end of the follow-up period of 14 days. Moreover,
      semiquantitative results were obtained when the PCR/hybridization results were
      analyzed by a phosphor imaging system. Immunohistochemistry and in situ
      hybridization from formaldehyde-fixed, paraffin-embedded specimens were highly
      similar in detecting viral components during the early stages of the myocardial
      injury. The results indicate that: (i) direct viral damage plays an essential
      role in acute murine CBV3-induced myocarditis, (ii) PCR appears a useful and
      sensitive diagnostic method in acute myocarditis, and (iii) immunohistochemistry
      as a specific and relatively rapid method might be practicable also in studying
      the early stages of acute myocarditis from archival clinical material.

PMID- 8551279
TI  - Comparison of monoclonal antibodies for immunostaining in the cytomegalovirus
      shell vial assay on 4,388 specimens.
AB  - The shell vial assay is a sensitive, rapid test for the detection of
      cytomegalovirus (CMV) in a variety of specimens. The sensitivity of this assay is
      dependent on a number of factors including the antibodies used for
      immunostaining. Monoclonal antibodies to the CMV major immediate-early antigen
      (p72) from Chemicon (MAB810) and Dupont (NEA-9221) were assessed side by side in
      duplicate vials on 4,388 specimens from a patient population consisting of > 90%
      organ transplant recipients. A total of 240 specimens (5.5%) were CMV positive in
      either one or both vials. Positivity rates were variable across different
      specimen types but highest (12.9%) in urine specimens. Of the positive specimens,
      175 (72.9%) tested positive in both vials, 43 (17.9%) tested positive in the
      Chemicon-stained vial only, and 22 (9.2%) tested positive in the Dupont-stained
      vial only (P < 0.01, McNemar's chi-square test). This gave an overall positivity
      rate of 5.0% for Chemicon antibodies and 4.5% for Dupont. There was no difference
      in the fluorescent focus counts produced by the two antibody sets. It is
      concluded that use of the Chemicon antibodies provides increased sensitivity of
      detection of CMV in the shell vial assay above that afforded by the Dupont
      antibody.

PMID- 8551280
TI  - Tumor necrosis factor-alpha and interferon-gamma inhibit synergistically viral
      replication in hepatitis B virus-replicating cells.
AB  - The effects of tumor necrosis factor-alpha and/or interferon-gamma on the
      replication of hepatitis B virus were examined using HB611 cells. These cells
      were derived from human hepatoblastoma cells, Huh6, by integrating hepatitis B
      virus DNA, and produce hepatitis B virus continuously. Each of the cytokines
      inhibited hepatitis B virus replication in the cells assessed as the amount of
      episomal hepatitis B virus DNA, without a decrease in cell viability. When the
      two cytokines were administered together, the inhibitory effect became greater.
      Incubation of the cells with 1,000 U/ml tumor necrosis factor-alpha decreased HBV
      DNA replicative intermediates by 55%, and that with 1,000 U/ml interferon-gamma
      decreased these by 51%. Furthermore, incubation with 1,000 U/ml tumor necrosis
      factor-alpha and 1,000 U/ml interferon-gamma in combination decreased HBV DNA
      replicative intermediates by 71%. In contrast, the amount of hepatitis B virus
      RNA and secretion of hepatitis B e antigen were not apparently reduced by the
      cytokines, and 2',5'-oligoadenylate synthetase activity was not detected in the
      supernatant. These results suggest that tumor necrosis factor-alpha and
      interferon-gamma inhibit hepatitis B virus replication by blocking some step in
      reverse transcription and that the 2',5'-oligoadenylate synthetase is not
      involved in the mechanism underlying the inhibition by these two cytokines.

PMID- 8551281
TI  - Biological phenotypes of HIV-1 subtypes A and B strains of diverse origins.
AB  - The identification of specific biologic phenotypic traits that can be correlated
      with different HIV-1 genetic subtypes was sought. The genetic subtypes were
      determined by either sequencing (Cameroonian strains, n = 18) or by the
      heteroduplex mobility assay (HMA) (Belgian strains, n = 21 and Ivorian strains, n
      = 25). Seventeen (81%) of the 21 Belgian isolates belonged to subtype B and 4
      (17%) were subtype A strains. Subtype A variants were predominant in the two
      African countries studied; 11 (61%) of 18 strains from Cameroon and 23 (92%) of
      25 strains from the Ivory Coast. Of the 64 isolates, 38 (58%) and 19 (29%)
      belonged to subtypes A and B, respectively. No significant difference was
      observed for biological phenotypes (slow/low and rapid/high) of both genetic
      subtypes. In symptomatic individuals, however, a significantly higher number of
      subtype B isolates were of rapid/high phenotype, compared with subtype A (5 of
      10; 50%) vs. 2 of 22; 9%), respectively; X2 = 6.7, P = 0.02). The findings
      suggest that overall HIV-1 isolates belonging to genetic subtype B are not
      distinguishable from subtype A variants on the basis of their biological
      phenotypes. Syncytium-inducing variants were less prevalent regardless of the
      geographic origin of the isolates.

PMID- 8551282
TI  - Significance of anti-hepatitis C virus core IgM antibodies in patients with
      chronic hepatitis C.
AB  - Antihepatitis C virus (HCV) IgM antibodies were found in patients with both acute
      and chronic hepatitis C. The aims of the study were to determine the
      significance, in terms of liver disease and virological parameters, of anti-HCV
      core IgM antibodies in the serum of patients with chronic hepatitis C, and the
      possible relationship between the presence of these antibodies before treatment
      and biochemical and virological responses to interferon therapy. Sixty-one
      patients with chronic hepatitis C were studied. Tests for serum anti-HCV core IgM
      antibodies were carried out before treatment. The patients received 3 mega units
      of interferon alpha-2a subcutaneously thrice weekly for at least 3 months (6
      months when alanine aminotransferase activity was normal at month 3). A
      biochemical response to interferon therapy was defined as normal alanine
      aminotransferase activity at the end of treatment (month 6: biochemical response)
      and 6 months later (month 12: sustained biochemical response). A sustained
      virological response was defined as serum HCV RNA negativity by a polymerase
      chain reaction-based detection method (PCR) in patients with normal alanine
      aminotransferase at month 12. Anti-HCV core IgM antibodies were detected in 28 of
      the 61 patients (46%). The prevalence of these antibodies was significantly
      higher in patients infected with HCV genotype 1 (including subtypes 1a and 1b)
      than in patients infected with other genotypes (including 2a and 3a) (57% vs.
      17%; P < 0.01). No significant difference was found between IgM-positive and IgM
      negative patients as regards the mean age, sex ratio, serum alanine
      aminotransferase and gamma-glutamyl transpeptidase activities, the prevalence of
      cirrhosis in liver biopsy specimens, detection of HCV RNA by PCR, and
      quantitation by branched DNA assay. At month 6 of interferon therapy, normal
      alanine aminotransferase activity was significantly more frequent in IgM-negative
      than in IgM-positive patients (52% vs. 21%, respectively; P < 0.02). At month 12,
      normal alanine aminotransferase activity and PCR negativity were significantly
      more frequent in IgM-negative than in IgM-positive patients (18% vs. 0%, P <
      0.04). It is concluded that anti-HCV core IgM antibodies in serum are
      significantly more frequent in patients infected by HCV type 1 than by other
      types. This suggests that their overall prevalence in patients with chronic
      hepatitis C in industrialized countries, where HCV type 1 accounts for the
      majority of infections, would be of the order of 50%, that anti-HCV core IgM
      antibodies are not associated with characteristic features of liver disease, and
      that their presence before treatment is associated with a failure of interferon
      alpha therapy to clear the virus.

PMID- 8551284
TI  - Dependent personality disorder. Age, sex, and axis I comorbidity.
AB  - In the present report, we analyzed the age, sex, and axis I comorbidity of a
      large sample of patients with dependent personality disorder, and compared the
      findings with those obtained in patients with other personality disorders. The
      sample consisted of 3640 consecutive hospital admissions with a DSM-III axis II
      diagnosis. Of the 342 patients with a dependent diagnosis, 51.2% were over 40
      years of age, compared with only 25.7% of the remaining patients with a
      personality disorder. The dependent sample was 69.6% female compared with 58.6%
      of those with other types of personality disorders. In general, dependent
      patients were more likely to have major depression and bipolar disorder than
      those with other personality disorders. Dysthymia and anxiety disorders occurred
      no more often than they did in the other personality disorders, as a whole. The
      rate of alcohol use disorders was lower than that observed in any other
      personality disorder except schizotypal. The rate of drug use disorders was
      intermediate between the lowest and highest rates in the other personality
      disorders.

PMID- 8551283
TI  - Short-term stability of HIV provirus levels in the peripheral blood of HIV
      infected individuals.
AB  - Changes in viral load have been reported to reflect disease progression or
      response to therapy; however, the stability of HIV DNA levels in HIV-infected
      individuals has not been extensively studied. Cellular HIV DNA levels in infected
      individuals were evaluated over a short time period to determine degree of
      variability as well as any correlation with other measurements of virus load or
      immune status. Peripheral blood mononuclear cells (PBMC) were obtained several
      times over 1 month from 32 asymptomatic or symptomatic non-AIDS, HIV-infected
      individuals currently on AZT therapy. PCR amplification of the HIV gag region was
      performed with DNA from PBMC lysates and the PCR amplified products quantitated
      by liquid phase hybridization. HIV DNA levels in the majority of the patients
      were relatively stable, with 26 of 32 persons having less than threefold change.
      Changes over the study period were both positive and negative, and the median
      change in HIV DNA levels was 68.6%. These changes were found to positively
      correlate with fluctuations in plasma p24 levels. In contrast, no correlations
      were found with other measurements of immune system activity, including changes
      in CD4 number, CD4 percent, and beta 2-microglobulin when compared with provirus
      changes. This study shows that levels of HIV DNA can be relatively stable over
      short periods in most non-AIDS, HIV-infected persons.

PMID- 8551285
TI  - The morbidity of DSM-III-R dependent personality disorder.
AB  - Dependent personality has long been discussed by clinicians, and by empirical
      researchers more recently. Little empirical evidence so far has been presented as
      the type and degree of disability with which it is associated. This report
      provides some empirical data in that regard. To examine this question, those with
      and without DSM-III-R dependent personality were compared in male veterans drawn
      from an outpatient psychiatry clinic (dependent and nondependent groups).
      Standardized interview assessments were used to determine axes I and II disorders
      and family history. The dependent personality disorder group had significantly
      lower socioeconomic status and poorer functioning in the family/home sphere. They
      had significantly more social phobia, borderline traits, and histrionic traits.
      In relatives, there was significantly more generalized anxiety disorder, simple
      phobia, drug abuse, and dramatic personality disorder cluster. There are clearly
      documentable vulnerabilities and morbidities associated with dependent
      personality disorder.

PMID- 8551286
TI  - Adolescent psychopathology as a function of informant and risk status.
AB  - Adolescents selected for delinquency risk in a community study, their parents,
      and teachers completed versions of the Child Behavior Checklist, with the raw
      scores representing the adolescents' level of psychopathology. All three
      informants rated high risk adolescents as showing higher levels of delinquency as
      well as other forms of psychopathology, particularly anxiety, aggression, social
      problems, thought problems, and, to a slightly less consistent extent, withdrawn
      behavior. In addition, compared with parents and adolescents, teachers rated
      psychopathology in African-American adolescents higher than that in Anglo
      American adolescents. The results are analyzed using knowledge drawn from social
      and child psychiatry.

PMID- 8551287
TI  - Perceptions of social pathology in the neighborhood and the etiology of narcotic
      addiction. A retrospective study.
AB  - In this study, we examined whether differential perceptions of poor urban
      neighborhoods may contribute to narcotic addiction in individuals who grow up in
      these neighborhoods. Three groups of adult males provided retrospective
      perceptions of the neighborhoods where they lived at ages 12 to 14. The groups,
      matched on neighborhood, age, and race, were: narcotic addicts, peer controls--a
      never-addicted control sample of age-11 associates of the addicts, and community
      controls--a never-addicted control sample of age-11 peers who did not associate
      with the addicts. Results suggested clear group differences in perceptions of
      neighborhood deviance, with addicts perceiving the greatest and community
      controls the least amount of deviance. However, within groups, subjects who lived
      in more socially deviant areas, as determined by official records, tended to view
      their neighborhoods as more deviant than did subjects who lived in less deviant
      neighborhoods.

PMID- 8551288
TI  - Predicting the DSM-V.
AB  - Using regression estimates based upon data about past editions of the DSM, we
      predict various features of the DSM-V. Included in these predictions are the date
      of publication, number of pages, total number of categories, number of categories
      defined using diagnostic criteria, total number of diagnostic criteria, color of
      the manual, who will be in charge of the task force that creates the DSM-V, and
      revenues generated by the DSM-V. This article ends with comments on the changes
      in the editions of the DSMs and an analogy to the Sorcerer's Apprentice.

PMID- 8551289
TI  - Prevalence of psychiatric disorders in medical inpatients.
AB  - The aim of the present study was to determine the prevalence of psychiatric
      disorders in acutely ill medical inpatients. A total of 313 consecutively
      admitted patients were interviewed using a semistructured psychiatric interview.
      Diagnoses were made according to DSM-IV diagnostic criteria during two time
      periods, the 7 days following admission and the month prior to admission. The
      results showed that 85 patients (27.2%) received a DSM-IV diagnosis, with several
      patients having comorbid diagnoses. Major depressive disorder was present in 16
      patients (5.1%), most of whom also had major depressive disorder in the month
      prior to admission. This prevalence rate is above that of the general population
      (1.2% to 2.8%), but less than that reported in most previous studies (20% to
      40%). Forty-three patients (13.7%) had an adjustment disorder, 18 patients (5.8%)
      had an anxiety disorder, and 17 patients (5.4%) had either alcohol dependence or
      abuse. Nurses were more proficient than medical staff at identifying patients who
      had received a DSM-IV diagnosis, recognizing 61% of cases compared with 41% for
      medical staff.

PMID- 8551290
TI  - Differences in dissociative experiences between survivors of childhood incest and
      survivors of assault in adulthood.

PMID- 8551291
TI  - A quasi-experimental comparison of the effectiveness of 6- versus 12-hour per
      week outpatient treatments for cocaine dependence.

PMID- 8551292
TI  - Cognitive performance in seasonal affective disorder: pattern recognition and the
      Stroop task.

PMID- 8551293
TI  - Musical hallucinations: interplay of degenerative brain disease, psychosis, and
      culture in a Chinese woman.

PMID- 8551294
TI  - Agoraphobia without panic: case illustrations of an overlooked syndrome.

PMID- 8551295
TI  - The dependent personality and interpersonal problems.
AB  - At the core of the dependent personality disorder lies an excessive reliance on
      other people for support, direction, and nurturance. However, because of their
      interpersonal style, many patients high in dependency have difficulties
      establishing and maintaining close interpersonal relationships. The present study
      examined interpersonal problems related to the dependent personality disorder.
      The relationships between dependency and interpersonal problems were examined in
      43 adult psychiatric inpatients and 66 nonpatient adults. All subjects were
      assessed for social functioning in terms of social behaviors typically displayed,
      density of their social networks, and subjective feelings of loneliness. Using
      correlations and multiple regression analyses, results showed that dependency was
      closely related to social behavior and quality of social networks for both
      psychiatric inpatients and nonpatient controls. Pearson correlations showed the
      dependent personality style was related to negative and disruptive interpersonal
      behaviors. Also, measures of social functioning were related to feelings of
      loneliness and depression. Finally, interpersonal dependency was strongly related
      to both depressive symptoms and depressive attitudes, especially in the
      psychiatric inpatients. The present findings demonstrate the importance of
      interpersonal dependency as related to interpersonal problems.

PMID- 8551296
TI  - Effect of wind velocity on suction trap catches of some Florida mosquitoes.
AB  - The correlations between wind velocity and suction trap catches of mosquitoes
      when taken at 15-min intervals during the night were studied at 2 locations.
      Although normal mosquito flight speeds are approximately 1 m/sec, trap catches
      were reduced about 50% by winds of 0.5 m/sec and 75% at 1.0 m/sec. Trap catches
      were inversely related to winds of all velocities and even the lightest winds
      reduced trap catches. No evidence was found for a threshold below which wind
      velocity had no effect.

PMID- 8551297
TI  - Mosquito productivity and surveillance for St. Louis encephalitis virus in
      Chicago during 1993.
AB  - The City of Chicago's Department of Health monitors weekly deposition of egg
      rafts of Culex species, prevalence of St. Louis encephalitis (SLE) virus-specific
      antibodies in feral birds, and prevalence of the virus in mosquito pools. The
      total number of Culex egg rafts collected in 1993 (4,623) was 2-fold greater than
      for the 1992 mosquito season. Virtually all of the early summer egg rafts were
      identified as Culex restuans. After the week of July 18, Culex pipiens accounted
      for 20-70% of the total rafts collected weekly. The prevalences for SLE viral
      antibodies (avian) and RNA (mosquitoes) were 0.2% and 0.02%, respectively. Both
      values were about 25-fold less than normally occur in epidemic years. It is
      important for practical considerations to continue this surveillance in order to
      recommend time- and site-specific mosquito abatement.

PMID- 8551298
TI  - Isolation of the insecticidal components of Tagetes minuta (Compositae) against
      mosquito larvae and adults.
AB  - Application of Tagetes minuta floral extract to silica gel column chromatography
      produced 2 fractions with the hydrogenate part 20-30 times more toxic to larvae
      and 12-13 times more toxic to adults of Aedes aegypti and Anopheles stephensi,
      respectively, than the oxygenate part. Further fractionation by column
      chromatography of the hydrogenate fraction produced 4 thiophenes, 5-(but-3-ene-1
      ynyl)-2,2'-bithiophene, 5-(but-3-ene-1-ynyl)-5'-methyl-2,2'-bithiophene,
      2,2',5',2"-terthiophene, and 5-methyl-2,2',5',2"-terthiophene. These compounds in
      Tagetes minuta are largely responsible for the toxicity exhibited against the
      tested mosquitoes.

PMID- 8551299
TI  - Efficacy of a 1:1 and 1:5 mixture of technical permethrin and piperonyl butoxide
      against Anopheles quadrimaculatus and Psorophora columbiae.
AB  - Anopheles quadrimaculatus and Psorophora columbiae adults were treated with a 1:1
      and 1:5 mixture of technical permethrin and piperonyl butoxide. These mixtures
      (0.00075 lb AI/acre) at 100, 200, and 300 ft. downwind of application killed a
      similar (P < or = 0.05) percentage of Ps. columbiae ranging from 45.1 to 68.8%
      and 85.7 to 100.0% after 1 and 24 h posttreatment, respectively. Similar results
      were obtained at 1 and 24 h posttreatment against An. quadrimaculatus (0.00075 lb
      AI/acre) where percentage mortality ranged from 42 to 62% and 63 to 78% after 1
      and 24 h posttreatment, respectively. At 24 h posttreatment, significantly more
      mortality (P < or = 0.05) occurred in An. quadrimaculatus than in Ps. columbiae
      for both the 1:1 and 1:5 formulations above, except at 100 ft. downwind. A higher
      dosage against An. quadrimaculatus (0.001 lb AI/acre) resulted in a higher mean
      mortality at 1 h posttreatment (45.1-79.1%) and 24 h posttreatment (59.2-86.0%)
      than at the lower dosage. A 25% increase in permethrin (0.001 lb AI/acre) vs. a
      400% increase in piperonyl butoxide alone gave increases in mortality of 30.4%
      vs. 8.6%, respectively.

PMID- 8551300
TI  - Characterization of resistance to organophosphate, carbamate, and pyrethroid
      insecticides in field populations of Aedes aegypti from Venezuela.
AB  - Resistance to the organophosphates (OP) temephos, malathion, and pirimiphos
      methyl, and the carbamate propoxur was found to be low (< 5-fold) in 3 Aedes
      aegypti populations collected from Falcon and Aragua states of Venezuela.
      Resistance to chlorpyrifos (OP), permethrin, and lambda-cyhalothrin (pyrethroids)
      was moderate (7-fold) in both populations. Mechanisms of resistance were
      investigated with the synergists piperonyl butoxide (mixed function oxidase
      inhibitor) and S, S, S-tributyl phosphorothioate (DEF, an esterase inhibitor).
      Nonspecific esterase and oxidase enzymes played a significant role in OP and
      carbamate resistance, respectively. Resistance to pyrethroid insecticides was not
      affected by DEF or piperonyl butoxide. This suggested the presence of another
      mechanism such as altered target site sensitivity (kdr). Biochemical tests showed
      significantly greater amounts of esterase activity in field strains, whereas
      insensitive acetylcholinesterase was not involved in either OP or carbamate
      resistance. These results must be considered in future control programs for Ae.
      aegypti, because OPs and pyrethroids are currently used in vector control in most
      countries of Central and South America.

PMID- 8551301
TI  - Metaphase karyotypes of Anopheles of Thailand and Southeast Asia: IV. The
      Barbirostris and Umbrosus species Groups, subgenus Anopheles (Diptera:
      Culicidae).
AB  - Metaphase karyotypes of 2 and 3 species of the Umbrosus and the Barbirostris
      Groups, respectively, of the subgenus Anopheles occurring in Thailand and
      Indonesia show inter- and intraspecific differences with respect to the amount
      and distribution of constitutive heterochromatin in the sex chromosomes and/or
      autosomes. Four forms of metaphase karyotypes have been recognized in the wild
      samples of Anopheles barbirostris based on differences in size and shape of X and
      Y chromosomes. It is not known whether forms A, B, and C of the metaphase
      karyotype of An. barbirostris found in Thailand represent inter- or intraspecific
      differences. However, form D, which occurs only in Indonesia, may represent a
      mitotic karyotype of a distinct species closely related to An. barbirostris.
      Anopheles campestris and An. barbumbrosus are each readily separated from An.
      barbirostris by mitotic chromosomes. Anopheles umbrosus and An. letifer of the
      Umbrosus Group also exhibit heterochromatin variation in the X chromosomes. These
      2 species can be readily distinguished by the gross morphology of mitotic
      karyotypes, particularly the X and Y chromosomes.

PMID- 8551302
TI  - Role of larval cadavers in recycling processes of Bacillus sphaericus.
AB  - The influence of larval cadavers of Culex pipiens on recycling processes of
      Bacillus sphaericus was investigated by bioassays and spore counts in the
      laboratory. Studies conducted with 3 different B. sphaericus concentrations
      (0.005, 0.01, 0.05 mg B. sphaericus/liter) indicated that the presence of
      cadavers in the water contributed to the maintenance of toxic levels of B.
      sphaericus. Larval cadavers seem to contain all the nutrients necessary both for
      vegetative multiplication and for toxin synthesis associated with the sporulation
      process. Bioassays of B. sphaericus revealed that the mortality of Culex pipiens
      remained on a high level over a period of 26 days when larval cadavers were added
      every second day to the test vessels. This result was supported by a sharp
      increase in spore density when cadavers were added at the same interval. The test
      series showed B. sphaericus recycles in intact cadavers of Culex pipiens, whereas
      this phenomenon could not be observed when crushed cadavers were used in the
      trials. Therefore, our results demonstrated that for successful recycling
      processes it seems of crucial importance that infected cadavers remain intact at
      least for a certain time and also that the dosage of the applied B. sphaericus
      plays a major role in recycling processes whereas larval density is only of minor
      importance to these processes.

PMID- 8551303
TI  - Cold storage effects on egg hatch in laboratory-reared Culicoides variipennis
      sonorensis (Diptera: Ceratopogonidae).
AB  - The effects of cold storage (5 degrees C) on the hatching rates of laboratory
      reared Culicoides variipennis sonorensis eggs were examined. Mortality increased
      with storage time. Average maximum embryo survivorship for 4 trials was 55.0 +/-
      4.2 (+/- SEM) days. Alternating daily cycles of high and then low mean hatching
      rates occurred and possibly were due to location differences in temperature
      within the temperature-controlled rearing system. During cold storage at 5
      degrees C, C. v. sonorensis eggs may be kept for ca. 28 days with an anticipated
      hatching rate of about 50%.

PMID- 8551304
TI  - Probing and gorging responses of three mosquito species to a membrane feeding
      system at a range of temperatures.
AB  - Membrane feeding of 3 mosquito species, Aedes aegypti, Anopheles stephensi, and
      Anopheles arabiensis, with formulated protein meals was carried out at a range of
      temperatures. The response was evaluated in terms of probing after 5 min,
      engorgement after 90 min, and 50% feeding time. Aedes aegypti showed a
      satisfactory feeding response across the complete temperature range investigated,
      28-40 degrees C, although engorgement was significantly faster between 36 and 40
      degrees C. Anopheles stephensi fed best between 32 and 40 degrees C. Anopheles
      arabiensis showed a poor probing and feeding response at all temperatures,
      although the best responses were recorded at 38-40 degrees C.

PMID- 8551305
TI  - Mosquito vector control and biology in Latin America--a fifth symposium.
      Portland, Oregon, March 1995. Abstracts.

PMID- 8551306
TI  - Field overwinter survivorship of Aedes albopictus eggs in Japan.
AB  - The overwintering ability of eggs of 3 temperate and 2 tropical strains of Aedes
      albopictus was assessed at 5 field sites during winter 1991-92 and 4 field sites
      during winter 1992-93 in Japan. Nagasaki, the warmest site, is the only site at
      which tropical Ae. albopictus could possibly become established. The eggs of
      temperate Ae. albopictus can survive less than half of the winters in Sapporo.
      Temperate Ae. albopictus can survive at least some of the winters at Bijo Daira,
      Kitakami, Nagasaki, Tokyo, and Toyama.

PMID- 8551307
TI  - Residual activity of three slow-release temephos formulations against Aedes
      aegypti larvae.
AB  - Residual effectiveness of plaster matrix formulations of temephos and temephos
      plus an emulsifier (Atlox 3409F) were evaluated against Aedes aegypti larvae
      during an 8-wk period. Formulations of 2% and 5% (AI) Atlox with 5% (AI) temephos
      yielded 100% larval mortality for 8 wk. A 5% temephos formulation without the
      addition of the emulsifier produced 100% larval mortality through only 1 wk.

PMID- 8551308
TI  - Estimating the gonotrophic cycle and survivorship of Simulium ochraceum (Diptera:
      Simuliidae) during routine vector surveillance in southern Mexico.
AB  - The gonotrophic cycle, survivorship, and daily parity rate of Simulium ochraceum
      were estimated from specimens collected during routine vector surveillance in
      southern Mexico, using a vertical (time-specific) method. Series of sequential
      data analysis on parity of the entomological data obtained in February 1994
      showed the highest significant (P < 0.05 alpha) correlation indices (r = 0.63 and
      r = 0.67) for a 4-day time lag, indicating that the mean gonotrophic cycle length
      corresponded to 4 days. Daily survival rate was estimated to be 0.80, the
      survival to infective age (12 days) to be 6.9%, and the daily parity rate to be
      0.41. These estimations are in accordance with those previously obtained by
      others from mark-release-recapture experiments (horizontal method) in Guatemala.

PMID- 8551309
TI  - Detoxifying esterases in Culex pipiens quinquefasciatus from the Caribbean
      countries.
AB  - Several over-produced esterases confer resistance to organophosphorus
      insecticides in the Culex pipiens complex. We describe their distribution in
      islands and countries of the Caribbean region based on new collections and
      previous studies, and discuss the need to: 1) undertake DNA studies to correctly
      identify the esterase B alleles that are amplified in different regions, and 2)
      investigate the variability among gene copies within each amplification system in
      order to fully understand their origin and their evolution through time.

PMID- 8551310
TI  - Occurrence of Culex (Melanoconion) erraticus (Diptera: Culicidae) in California.
AB  - Culex erraticus is added to the 52 currently recognized mosquito species from
      California. Four females and one male were collected in a CO2 trap on August 29,
      1994, at the Imperial Wildlife Refuge, Wister Unit, Imperial County, CA.
      Additional specimens were collected on October 24, and larval habitats were
      located on October 31, 1994. Possible routes of introduction are discussed.

PMID- 8551311
TI  - Evaluation of enemas for exposing Aedes aegypti to suspensions of dengue-2 virus.
AB  - To determine if enemas could be used to simulate oral exposure of Aedes aegypti
      to dengue-2 virus, we compared infection rates of mosquitoes administered an
      enema of a blood suspension containing dengue-2 virus to infection rates in
      mosquitoes that imbibed the same suspension from a drop of blood. In 1 of 4
      experiments infection rates were significantly different. More importantly,
      during 2 of the 4 trials, 100% of the mosquitoes in the enema treatment group
      were infected. We speculate that the capillary tube used to administer the enemas
      abraded the hindgut of mosquitoes in the groups with 100% infection rates and,
      therefore, virus was inoculated directly into the mosquitoes' hemocoel. We
      conclude that the method we used for administering enemas cannot be used to
      simulate oral exposure of Ae. aegypti to dengue-2 virus.

PMID- 8551312
TI  - Failure of immune sera to neutralize dengue-2 virus in intrathoracically
      inoculated Aedes aegypti.
AB  - Aedes aegypti became infected when inoculated with a mixture of dengue-2 virus
      and anti-dengue-2 antibodies, but not when they were exposed to the same mixture
      per os. This phenomenon merits more detailed investigation. Understanding why
      this difference in mosquito infection rate occurs may lead to improved dengue
      virus assays or provide insights into the nature of dengue virus-antibody
      interactions.

PMID- 8551313
TI  - Notes on the biology of Orthopodomyia in Illinois.
AB  - The principal habitats of immature Orthopodomyia alba and Orthopodomyia signifera
      are tree holes, though they are occasionally encountered in artificial
      containers. We collected 929 Or. alba and 17 Or. signifera from 2 plastic trash
      cans, 2 scrap tires, and a tree hole. All collections were made in an urban
      residential area in central Illinois.

PMID- 8551314
TI  - Proportionality between light trap catches and biting densities of malaria
      vectors.

PMID- 8551315
TI  - Early-onset encephalomyopathy associated with tissue-specific mitochondrial DNA
      depletion: a morphological, biochemical and molecular-genetic study.
AB  - A male infant, born from consanguineous parents, suffered from birth with a
      progressive neuromuscular disorder characterized by psychomotor delay, hypotonia,
      muscle weakness and wasting, deep-tendon areflexia and spastic posture. High
      levels of lactic acid in blood and cerebrospinal fluid suggested a mitochondrial
      respiratory chain defect. Muscle biopsy revealed ragged-red and cytochrome c
      oxidase-negative fibres, lipid accumulation and dystrophic changes. Multiple
      defects of respiratory complexes were detected in muscle homogenate, but cultured
      fibroblasts, myoblasts and myotubes were normal. Southern blot analysis showed
      markedly reduced levels of mitochondrial DNA (mtDNA) in muscle, while
      lymphocytes, fibroblasts and muscle precursor cells were normal. Neither
      depletion of mtDNA nor abnormalities of the respiratory complexes were observed
      in innervated muscle fibres cultured for as long as 4 months. No mutations were
      observed in two candidate nuclear genes, mtTFA and mtSSB, retro-transcribed,
      amplified and sequenced from the proband's mRNA. Sequence analysis of the mtDNA D
      loop and of the origin of replication of the mtDNA light strand failed to
      identify potentially pathogenic mutations of these replicative elements in the
      proband's muscle mtDNA. Our findings indicate that mtDNA depletion is due to a
      nuclear encoded gene and suggest that the abnormality underlying defective mtDNA
      propagation must occur after muscle differentiation in vivo.

PMID- 8551316
TI  - Visual assessment of medial temporal lobe atrophy on magnetic resonance imaging:
      interobserver reliability.
AB  - We conducted an interobserver study to assess agreement on visual rating of
      medial temporal lobe atrophy on coronal T1-weighted MRI. A total of 100 studies
      of elderly individuals, using two different MRI techniques (spin echo and
      inversion recovery sequences), were analysed by four raters (three neurologists
      and one neuroradiologist) using a five-point rating scale. Complete agreement was
      found in 37% of the total sample. Interobserver agreement as expressed by kappa
      values was 0.44 (95% CI = 0.34-0.54) and 0.51 (95% CI = 0.41-0.61) for the two
      techniques. After dichotomizing medial temporal lobe atrophy into present or
      absent, a post hoc analysis revealed higher complete agreement (70%), with kappa
      values of 0.59 (95% CI = 0.51-0.67) and 0.62 (95% CI = 0.48-0.075), for the two
      techniques (all four raters). From this study we conclude that visual rating of
      medial temporal lobe atrophy on MRI in the coronal plane yields fair to good
      agreement among observers. We recommend this type of visual rating for use in
      clinical settings when a quick judgement on the presence of medial temporal lobe
      atrophy is needed.

PMID- 8551317
TI  - Propofol analgesia in central pain: preliminary clinical observations.
AB  - Propofol, an intravenous general anaesthetic, has been reported to relieve some
      forms of pruritus at subhypnotic doses. We assessed its effectiveness in 32
      patients with several kinds of non-malignant chronic pain, in a placebo
      controlled, double-blind study. We found that central pain, but not neuropathic
      pain, is at least partially controlled by propofol at subhypnotic doses, without
      major side-effects. In particular, allodynia associated with central, but no
      neuropathic, pain has been completely controlled. Propofol analgesia leads to
      renormalization of brain metabolism as seen on single photon emission computed
      tomography. We conclude that propofol may help in the diagnosis of central pain,
      particularly in unclear cases, and also in treatment. Possible mechanisms of
      action are discussed.

PMID- 8551318
TI  - Unimanual motor learning impaired by frontomedial and insular lesions in man.
AB  - We correlated impaired unimanual motor learning with the lesion site in 53
      patients with chronic lesions predominantly of the frontal lobe. The lesions were
      assessed using computed tomography (CT), then transferred to standard templates
      of nine slices parallel to the canthomeatal plane and digitized with a raster
      matrix of 3 mm by 3 mm width. The learning task was to track a moving target on a
      computer screen with a dot guided by the preferred hand, while the horizontal
      coupling between hand movement and screen was inverted. The mean tracking error
      was recorded over eight successive trials of 80s duration. If the mean error of
      the last three trials was not lower than that of the first three trials, impaired
      motor learning was assumed. We correlated performance and lesion with a
      contingency table analysis for each raster element. Impaired motor learning was
      associated with a lesion within the supplementary motor area and adjacent
      anterior cingulate, and within the anterior insular region. Our results indicate
      that these regions are critical for motor learning and functional plasticity in
      man. Our data support activation patterns obtained with positron emission
      tomography.

PMID- 8551319
TI  - The contribution of single photon emission tomography to the clinical
      differentiation of degenerative cortical brain disorders.
AB  - The accurate clinical diagnosis of degenerative cortical brain disorders is a
      necessary prerequisite for patient management and the critical evaluation of new
      treatments. This study has evaluated the ability of single photon emission
      tomography (SPET) to differentiate between Alzheimer's disease (AD) and different
      forms of non-Alzheimer lobar atrophy (LA), using a multi-purpose system in
      widespread routine clinical use. 99mTc-HMPAO SPET was carried out in patients
      with AD and three clinical syndromes associated with LA: frontotemporal dementia
      (FTD), progressive non-fluent aphasia (PA) and semantic dementia (SD). Principal
      component (PC) analysis was performed on regional cerebral blood flow (rCBF) data
      and inter-group comparisons were performed for PC scores using multiple t-tests.
      Three PCs explained 86.5% of the variation in rCBF values between individual
      patients and normal controls. The first PC reflected the average rCBF value and
      separated patient groups from normal controls but failed to distinguish between
      patient groups. The second PC reflected anterior-posterior asymmetry and
      separated AD from all three forms of LA. This PC also separated FTD and SD from
      controls but failed to distinguish between FTD, PA and SD. The third PC reflected
      left-right asymmetry and separated PA from all other groups. 99mTc-HMPAO SPET is
      able to differentiate between degenerative cortical brain disorders in a simple
      and physiological meaningful way, thereby showing considerable potential as a
      routine tool in the clinical evaluation and differentiation of AD and LA.

PMID- 8551320
TI  - The Rivermead Post Concussion Symptoms Questionnaire: a measure of symptoms
      commonly experienced after head injury and its reliability.
AB  - After head injuries, particularly mild or moderate ones, a range of post
      concussion symptoms (PCS) are often reported by patients. Such symptoms may
      significantly affect patients' psychosocial functioning. To date, no measure of
      the severity of PCS has been developed. This study presents the Rivermead Post
      Concussion Symptoms Questionnaire (RPQ) as such a measure, derived from published
      material, and investigates its reliability. The RPQ's reliability was
      investigated under two experimental conditions. Study 1 examined its test-retest
      reliability when used as a self-report questionnaire at 7-10 days after injury.
      Forty-one head-injured patients completed an RPQ at 7-10 days following their
      head injury and again approximately 24 h later. Study 2 examined the
      questionnaire's inter-rater reliability when used as a measure administered by
      two separate investigators. Forty-six head-injured patients had an RPQ
      administered by an investigator at 6 months after injury. A second investigator
      readministered the questionnaire approximately 7 days later. Spearman rank
      correlation coefficients were calculated for ratings on the total symptom scores,
      and for individual items. High reliability was found for the total PCS scores
      under both experimental conditions (Rs = + 0.91 in study 1 and Rs = + 0.87 in
      study 2). Good reliability was also found for individual PCS items generally,
      although with some variation between different symptoms. The results are
      discussed in relation to the major difficulties involved when looking for
      appropriate experimental criteria against which measures of PCS can be validated.

PMID- 8551321
TI  - Intrathecal synthesis of IgG in benign intracranial hypertension: a re
      examination.
AB  - In a previous retrospective study, 4 of 9 patients with benign intracranial
      hypertension were unexpectedly positive for intrathecal synthesis of
      immunoglobulin (Ig) G by quantitative measurement (log IgG index). This was
      remarkable as the only disease among many studied that showed such a discrepancy.
      A further study was done, now prospectively. Log IgG index values were elevated
      in 2 of the 11 new cases. As before, qualitative measurement (isoelectric
      focusing) gave uniformly negative results. Five of the 6 instances where the log
      IgG index was elevated could be accounted for, in fact, by abnormal values of
      constituent variables other than cerebrospinal fluid IgG. Quantitative tests for
      intrathecal synthesis of IgG can give misleading results on their own.
      Immunological mechanisms most probably are not involved in the pathogenesis of
      benign intracranial hypertension.

PMID- 8551322
TI  - Repetition and the arcuate fasciculus.
AB  - According to the traditional model of language organization, repetition deficits
      arise following damage to the arcuate fasciculus of the dominant hemisphere
      (conduction aphasia). Conduction aphasia may result from lesions that spare the
      arcuate fasciculus. However, these patients have atypical language organization.
      We describe a man with normal language architecture who underwent a resection of
      the anterior portion of his arcuate fasciculus and retained his ability to repeat
      words and sentences. We propose that the arcuate fasciculus is not necessary for
      speech repetition by the lexical route.

PMID- 8551323
TI  - Anti-beta-tubulin antibodies have no diagnostic value in patients with chronic
      inflammatory demyelinating polyneuropathy.
AB  - High-titre anti-beta-tubulin antibodies were recently reported to occur in over
      50% of sera from patients with chronic inflammatory demyelinating polyneuropathy
      (CIDP). It was concluded that these antibodies may help to distinguish CIDP from
      other neuropathies and that they are diagnostically useful. To verify these
      findings, we studied sera of 43 CIDP patients, only 3 of whom had anti-beta
      tubulin antibodies. The differences between the results obtained cannot fully be
      explained by differences between patients or antigens but may be explained by the
      use of different techniques (Western blot versus ELISA). We used Western blot,
      which is less sensitive but far more specific, to detect these antibodies. The
      findings of our study did not confirm the high frequency of selective high-titre
      anti-beta-tubulin antibodies in CIDP patients. Therefore we conclude that binding
      to beta-tubulin by Western blot cannot serve as a marker of CIDP.

PMID- 8551324
TI  - Neuroborreliosis as a cause of respiratory failure.
AB  - We report three cases of neuroborreliosis presenting with acute respiratory
      impairment. All the patients had encephalopathy and focal neurological signs with
      brain stem abnormalities in two. All three patients had respiratory arrest
      associated with progressive nocturnal hypoventilation or prolonged central
      apnoea. Tracheostomy and prolonged periods of ventilatory support were necessary
      in all cases and weaning was complicated by residual central respiratory
      disturbances. These cases emphasise that Borrelia infection should be considered
      in the differential diagnosis of unexplained respiratory failure.

PMID- 8551325
TI  - Head tremor due to bilateral thalamic and midbrain infarction.

PMID- 8551326
TI  - Lhermitte's sign in pseudotumour cerebri.

PMID- 8551327
TI  - Presynaptic facilitation revisited: state and time dependence.
AB  - The mechanisms underlying short-term presynaptic facilitation, the enhancement of
      transmitter release from sensory neurons in Aplysia, induced by serotonin (5-HT),
      can be divided into two categories: (1) changes in ionic conductances leading to
      spike broadening and enhancement of Ca2+ influx; and (2) actions on the machinery
      for transmitter release that are independent of spike broadening and the
      resulting increases in Ca2+ influx. Spike broadening and the associated
      enhancement of excitability are induced by the modulation of K+ conductances in
      the sensory neuron. The cellular mechanisms that contribute to the enhancement of
      release that is independent of spike broadening are not known and may involve
      vesicle mobilization or other steps in exocytotic release. These two facilitatory
      actions of 5-HT are mediated by at least two second-messenger-activated protein
      kinase systems, protein kinase A (PKA) and protein kinase C (PKC). These two
      second-messenger cascades overlap in their contributions to synaptic
      facilitation. However, their relative contributions to enhancement of transmitter
      release are not simply synergistic but are state- and time-dependent. The state
      dependence is a reflection of the synapse's previous history of activity. When
      the synapse is rested (and not depressed), a brief pulse of 5-HT (lasting from 10
      sec to 5 min) produces its actions primarily through PKA via both spike
      broadening-dependent and -independent mechanisms. The broadening primarily
      involves the modulation of a voltage-dependent K+ current, IKV, with a small
      contribution by a voltage-independent K+ current, IKS. By contrast, the
      enhancement of excitability is mediated primarily by the modulation of IKS. As
      the synapse becomes depressed with repeated activity, the contribution of PKC
      becomes progressively more important. As is the case with PKA, PKC produces its
      action both by broadening the spike via modulation of IKV and by a spike
      broadening-independent mechanism. In addition to being state-dependent, the
      mechanisms of facilitation are time-dependent. There are differences in the
      response to 5-HT when it is given briefly to produce short-term facilitation or
      when the exposure is prolonged. When exposure is brief (< or = 5 min), PKA
      dominates. When exposure is prolonged (10-20 min), PKC becomes dominant as it is
      with depressed synapses. Thus, synaptic plasticity appears to be expressed in
      several overlapping time domains, and the transition between very short-term
      facilitation and various intermediate duration phases seems to involve
      interactive processes between the kinases.

PMID- 8551328
TI  - The dopamine transporter is localized to dendritic and axonal plasma membranes of
      nigrostriatal dopaminergic neurons.
AB  - Nigrostriatal dopaminergic neurons play an essential role in the central
      regulation of motor functions. These functions are initiated through the release
      of dopamine from axon terminals in the striatum or from dendrites in the
      substantia nigra (SN) and are terminated by the reuptake of dopamine by the
      sodium- and chloride-dependent dopamine transporter (DAT). DAT also can transport
      dopamine neurotoxins and has been implicated in the selective vulnerability of
      nigrostriatal dopaminergic neurons in major models of Parkinson's disease. We
      have used electron microscopic immunocytochemistry with an N-terminal domain anti
      peptide antibody to examine the subcellular distribution of DAT in the rat SN and
      dorsolateral striatum. In the SN, immunogold labeling for DAT was localized to
      cytoplasmic surfaces of plasma membranes and smooth endoplasmic reticulum of
      dendrites and dendritic spines, few of which contained synaptic vesicles.
      Neuronal perikarya in the SN contained immunogold-labeled pleomorphic electron
      lucent tubulovesicles but showed immunolabeling of plasma membranes only rarely.
      Axon terminals in the striatum contained extensive immunogold labeling of
      cytoplasmic surfaces of plasma membranes near aggregates of synaptic vesicles and
      less frequent labeling of intervaricose segments of plasma membrane or small
      electron-lucent vesicles. In sections dually labeled for DAT and the
      catecholamine-synthesizing enzyme tyrosine hydroxylase, both markers were
      colocalized in most profiles in the SN and striatum. These findings support the
      proposed topological model for DAT and suggest that this transporter is
      strategically located to facilitate uptake of dopamine and neurotoxins into
      distal dendritic and axonal processes of nigrostriatal dopaminergic neurons.

PMID- 8551329
TI  - A novel neuronal P2x ATP receptor ion channel with widespread distribution in the
      brain.
AB  - There is strong evidence that ATP acts as an excitatory neurotransmitter in the
      periphery, yet little is known about fast central ATP-mediated transmission. We
      report here the molecular cloning of a novel neuronal ionotropic ATP receptor of
      the P2x subtype (P2x3) isolated from rat brain. This central P2x channel subunit
      has significant amino acid homology with two recently cloned ATP-gated channels
      from rat smooth muscle (47%) and pheochromocytoma PC12 cells (37%). P2x3 receptor
      contains the characteristic 10 conserved cysteines of ATP-gated channels, a
      putative extracellular region homologous to the Walker type A motif found in
      various nucleotide-binding proteins, and two potential sites for phosphorylation
      by protein kinase C. Homomeric receptor P2x3 channels expressed in Xenopus
      oocytes produce rapid cation-selective purinergic currents that are potentiated
      by zinc ions and reversibly blocked by the P2x antagonists suramin, Reactive Blue
      2, and pyridoxalphosphate-6-axophenyl-2U,4U-disulfonic acid. P2x3-receptor
      subunit mRNA is found in the Purkinje cells and the granule cells of the
      cerebellum as well as in CA3 pyramidal cells of the hippocampus that are
      innervated by zinc-rich axon terminals of mossy fibers. Our results suggest that
      fast excitatory synaptic transmission mediated by zinc-sensitive ATP-gated
      channels is widespread in mammalian brain.

PMID- 8551330
TI  - Fractional calcium current through neuronal AMPA-receptor channels with a low
      calcium permeability.
AB  - The Ca(2+)-permeation properties of AMPA-receptor (AMPA-R) channels in Purkinje
      neurons in rat cerebellar slices were studied using a combination of whole-cell
      patch-clamp recordings, Fura-2 fluorometry, and single-cell reverse-transcription
      (RT)-PCR. Several lines of evidence indicate that Purkinje neurons, at both early
      and late stages of postnatal development, express exclusively AMPA-R channels
      with a low Ca2+ permeability. First, no Ca2+ signal was detected during
      application of either AMPA or kainate to Purkinje neurons loaded with the Ca2+
      indicator Fura-2 AM. In contrast, kainate application induced large Ca2+
      transients in Bergmann glia cells. Second, in ion substitution experiments, when
      Ca2+ is the only extracellular permeant cation, the reversal potential
      corresponds to that expected for AMPA-R channels with a low permeability for
      Ca2+. Third, using a fluorometric flux-measurement approach (Schneggenburger et
      al., 1993a), we found that the Ca2+ fraction of the total cation current through
      AMPA-R channels is approximately 0.6%. This value is approximately sixfold lower
      than that found for recombinant AMPA-R lacking the AMPA-R subunit GluR2.
      Furthermore, single-cell RT-PCR experiments revealed the presence of the AMPA-R
      subunits GluR1, GluR2, and GluR3 in Purkinje neurons in cerebellar slices at
      developmental stages corresponding to those studied electrophysiologically. The
      expression of GluR2 in all cells tested (n = 14) is consistent with the subunit
      composition predicted from studies of recombinant AMPA-R channels with a low
      permeability for Ca2+ (Burnashev et al., 1992b). In conclusion, this study
      establishes that cerebellar Purkinje neurons at all postnatal developmental
      stages possess AMPA-R channels with a low permeability for Ca2+.

PMID- 8551331
TI  - Molecular and developmental characterization of novel cDNAs of the myelin
      associated/oligodendrocytic basic protein.
AB  - Several novel myelin-associated/oligodendrocytic basic protein (MOBP) isoforms
      were identified in this study by cDNA cloning. They are small, highly basic
      polypeptides comprising 69, 81, and 99 amino acids (8.2, 9.7, and 11.7 kDa,
      respectively) and show no significant homology with described proteins or domain
      structures. All (as yet) identified MOBP isoforms are identical in amino acids 1
      68 but differ in the length and polarity of the C-terminal region. One isoform,
      designated MOBP81, was shown to be expressed abundantly during development.
      Interestingly, MOBP81 has a significant clustering of positively charged residues
      at positions 69-81, a feature that also has been observed for myelin basic
      protein (MBP) and Po. As demonstrated by in situ hybridization, MOBP gene
      expression occurs during development of the rat optic nerve later than that of
      MBP and proteolipid protein and coincides exactly with the beginning of myelin
      compaction. The 2.6 kb MOBP81-A transcript is localized in the processes of
      oligodendrocytes, whereas the 3.8 kb MOBP81-B transcript is restricted to the
      perinuclear region. Therefore, MOBP81-A and related mRNAs seem to be transported
      to the periphery of the oligodendrocytes, as is known for the transcripts of the
      MBP gene. The late developmental expression of the MOBP gene suggests that the
      MOBP proteins act at the late steps of myelin formation, possibly in myelin
      compaction and in the maintenance of the myelin sheath.

PMID- 8551332
TI  - Regulatory differences in the stress response of hippocampal neurons and glial
      cells after heat shock.
AB  - During periods of stress, cells depend on a transient, highly conserved, and
      regulated response to maintain homeostasis. This "heat shock response" is
      mediated transcriptionally by a multigene family of heat shock factors (HSF). The
      presence of multiple HSF suggests that activation of a given HSF is stress
      specific. Using Western blot analysis, we have demonstrated the inability of
      primary cultured rat hippocampal neurons to induce a heat shock response after
      hyperthermia. In contrast, secondary cultured rat glial cells demonstrated a
      robust response. Examination of whole-cell extracts from the two cell types with
      gel shift mobility analysis and Western blot analysis revealed that although
      glial cells express HSF1 and HSF2, hippocampal neurons only express HSF2.
      Incubation of whole-cell extracts with monoclonal antisera raised against HSF1
      and HSF2 before gel shift mobility analysis demonstrated HSF1 DNA-binding
      activity in glial cells and HSF2 DNA-binding activity in neurons. HSF1 has been
      shown to be the principal mediator of heat-induced heat shock gene expression.
      These results suggest that the deficient heat shock response of hippocampal
      neurons at this developmental stage is attributable to a lack of HSF1 expression.
      Furthermore, these results suggest that considerations of selective neuronal
      vulnerability to environmental stress should include the principal mediators of
      the stress response, the HSF.

PMID- 8551333
TI  - Overexpression of Bcl-2 with herpes simplex virus vectors protects CNS neurons
      against neurological insults in vitro and in vivo.
AB  - Previous studies have demonstrated that overexpression of the proto-oncogene bcl
      2 can protect neuron and neuron-like cell lines from growth factor deprivation,
      calcium ionophores, glutamate excitotoxicity, hypoglycemia, free radicals, and
      lipid peroxidation. To determine whether Bcl-2 exhibits a similar protective
      effect in CNS neurons, we generated defective herpes simplex virus (HSV) vectors
      capable of overexpressing Bcl-2 in primary cultures and in the intact brain.
      Infection of hippocampal cultures with Bcl-2 vectors enhanced neuron survivorship
      after exposure to adriamycin, a potent oxygen radical generator. Furthermore,
      dichlorofluorescein measurements indicated that there was a significant reduction
      in the accumulation of oxygen radicals associated with this insult. Bcl-2 vectors
      also enhanced survival in cultured neurons after exposure to glutamate and
      hypoglycemia. Most significantly, the in vivo delivery of the vector protected
      neurons against adriamycin toxicity in the dorsal horn of the dentate gyrus and
      focal ischemia in the striatum.

PMID- 8551334
TI  - Increased antioxidant enzyme activity in amyloid beta protein-resistant cells.
AB  - Clones of the rat pheochromocytoma cell line PC12 were selected for their
      resistance to amyloid beta protein (A beta). These A beta-resistant cells also
      survive higher concentrations of exogenously applied peroxides than the parent
      cells. A beta triggers intracellular H2O2 accumulation in the parent PC12 cells
      but not in the A beta-resistant cells. The absence of H2O2 accumulation in A beta
      resistant cells is not attributable to differences in A beta binding to the cell
      surface. However, the mRNA and protein levels of catalase and glutathione
      peroxidase, as well as the corresponding enzyme activities, are highly elevated
      in A beta-resistant clones. These activities correlate well with the increased
      resistance of cells to A beta or peroxides. Finally, cells transfected with
      catalase and glutathione peroxidase are also more resistant to A beta toxicity.
      These results indicate that increased antioxidant enzyme activities in A beta
      resistant cells account for at least part of their resistance to A beta and
      substantiate further the role of H2O2 in A beta toxicity.

PMID- 8551335
TI  - Developmental expression and functional characterization of the potassium-channel
      subunit Kv3.1b in parvalbumin-containing interneurons of the rat hippocampus.
AB  - The expression of the voltage-gated K(+)-channel subunit Kv3.1b in the developing
      hippocampus was determined by immunoblot and immunohistochemical techniques.
      Kv3.1b protein was detected first at postnatal day (P) 8. The Kv3.1b
      immunopositive cell number per tissue section reached a maximum at P14 and was
      maintained through P40. In contrast, the Kv3.1b protein content of isolated
      membrane vesicles in immunoblots progressively increased through P40, suggesting
      an increase in Kv3.1b content per cell throughout this time period. Kv3.1b
      protein was expressed selectively in the somata, proximal dendrites, and axons of
      cells lying within or near the pyramidal cell layer, consistent with their being
      GABAergic inhibitory interneurons. Kv3.1b was present in approximately 80% of
      parvalbumin-positive interneurons. The developmental onset of Kv3.1b and
      parvalbumin immunoreactivity was identical. In contrast, Kv3.1b was mostly absent
      from the subset of somatostatin-positive inhibitory interneurons.
      Electrophysiological recordings were made from stratum pyramidale interneurons in
      which morphology and Kv3.1b-positive immunoreactivity were confirmed post hoc.
      Outward currents had voltage-dependent and biophysical properties resembling
      those of channels formed by Kv3.1b. The current blocked by low concentrations of
      4-aminopyridine (4-AP) showed marked inactivation, suggesting that Kv3.1b may
      coassemble with other members of the Kv3 subfamily. In current-clamp recordings,
      concentrations of 4-AP that blocked the current through Kv3.1b channels allowed
      us tentatively to assign a role to Kv3.1b-containing channels in action-potential
      repolarization. These data demonstrate that Kv3.1b is regulated developmentally
      in a specific subpopulation of hippocampal interneurons and that channels
      containing this subunit may be a major determinant in imparting "fast-spiking"
      characteristics to these and other cells throughout the central nervous system
      containing the Kv3.1b subunit.

PMID- 8551337
TI  - Microtubule assembly and turnover in growing axons.
AB  - We have shown previously that axonal microtubules (MTs) are composite, consisting
      of two distinct domains that differ in their content of tyrosinated alpha-tubulin
      (tyr-tub). One domain is poor in tyr-tub and is situated at the minus end of the
      MT. The other domain is rich in tyr-tub and extends from the plus end of the tyr
      tub-poor domain to the end of the MT. We have proposed that the spatial variation
      in the relative content of tyr-tub along individual MTs reflects corresponding
      variations in their dynamic properties. The present experiments have tested this
      hypothesis directly by microinjecting biotin-labeled tubulin (Bt-tub) into
      cultured sympathetic neurons and then quantifying the appearance of Bt-tub in the
      tyr-tub-rich and tyr-tub-poor polymer of the axon. Bt-tub appeared in axonal MTs
      with a half-life (t1/2) of approximately 2.2 hr. This time course reflected an
      average of two distinct components corresponding to the tyr-tub-rich and tyr-tub
      poor polymer that had apparent t1/2 values of approximately 1.3 and 3.3 hr,
      respectively. In individual MTs, Bt-tub first appeared in the tyr-tub-rich domain
      and then only later appeared in the tyr-tub-poor domain. Also, the appearance of
      Bt-tub in the tyr-tub-rich polymer typically began precisely at its origin from
      the tyr-tub-poor domain, indicating that the tyr-tub-poor polymer is assembly
      competent and nucleates the assembly of tyr-tub-rich polymer locally within the
      axon. The stability properties of axonal MTs are discussed in terms of organizing
      MT assembly locally in the axon and generating long MTs for growing long axons.

PMID- 8551336
TI  - Developmental regulation of the toxin sensitivity of Ca(2+)-permeable AMPA
      receptors in cortical glia.
AB  - We examined the properties of glutamate agonist-induced Ca2+ fluxes in cultured
      CG-4 and O-2A progenitor cells from rat cortex. Kainate-induced Ca2+ fluxes in
      these cells were found to be attributable to the activation of AMPA receptors.
      Thus, these fluxes were enhanced by cyclothiazide but not by concanavalin A and
      were blocked completely by GYKI-53655. We simultaneously examined kainate-induced
      Ca2+ entry and Na+ currents in these cells under voltage-clamp conditions. Both
      of these parameters were blocked by Joro spider toxin (JSTx) in undifferentiated
      cells. However, neither JSTx nor Argiotoxin 636 effectively blocked either
      parameter in cells differentiated into type II astrocytes. This change in toxin
      sensitivity occurred slowly over a period of several days. Similar results were
      obtained in Ca(2+)-imaging studies. When cells were differentiated into
      oligodendrocytes, they showed an intermediate sensitivity to block by JSTx as
      assessed using imaging and voltage-clamp studies. Analysis of the expression of
      AMPA-receptor subunits showed an increase in the concentration of glutamate
      receptor-2 (GluR2) in CG-4 cells as they differentiated into type II astrocytes
      and oligodendrocytes. These results demonstrate that the AMPA receptors in cells
      of the O-2A lineage flux appreciable amounts of Ca2+ but may contain variable
      amounts of edited GluR2 subunits.

PMID- 8551338
TI  - Mechanisms of secondary injury to spinal cord axons in vitro: role of Na+, Na(+)
      K(+)-ATPase, the Na(+)-H+ exchanger, and the Na(+)-Ca2+ exchanger.
AB  - There is evidence that intracellular Na+ entry potentiates hypoxic-ischemic cell
      death by causing cytotoxic cell edema, intracellular acidosis, and gating of Ca2+
      entry by reverse activation of the Na(+)-Ca2+ exchanger. In this study, we
      examined the role of Na+ in mediating traumatic injury to spinal cord axons.
      Dorsal column segments from adult rats (n = 87) were isolated and maintained in
      an in vitro recording chamber while being superfused with oxygenated Ringer's
      solution (95% O2/5% CO2, 25 degrees C). Selected experiments (n = 10) also were
      done at 33 degrees C. Compound action potentials (CAP) were recorded from
      microelectrodes. Injury was performed by compression of the dorsal column segment
      for 15 sec with a modified aneurysm clip exerting a closing force of 2 gm. With
      injury, the CAP decreased to 72.1 +/- 9.6% of baseline values. Removal of
      extracellular Na+ and replacement with the impermeant cation N-methyl-D-glucamine
      enhanced recovery of the CAP to 98.3 +/- 18.3% (p < 0.05) of baseline. The Na+
      channel blockers tetrodotoxin and procaine also improved recovery of the CAP to
      96.3 +/- 23.7% (p < 0.05) and 82.8 +/- 4.6% (p < 0.05) of baseline values,
      respectively. In contrast, increasing Na+ permeability with veratridine resulted
      in greater attenuation of CAP amplitude after 1 hr of trauma (60.1 +/- 8.4%, p <
      0.05). Similarly, prevention of extrusion of Na+ from the intracellular
      compartment by inhibiting the Na(+)-K(+)-ATPase pump with ouabain resulted in
      greater attenuation of CAP amplitude at 1 hr after trauma (56.7 +/- 3.6%, p <
      0.05). The Na(+)-H+ exchange blockers amiloride (100 microM) and harmaline (100
      microM) significantly improved recovery after injury to 89.6 +/- 17.0% (p < 0.05)
      and 85.7 +/- 7.2% (p < 0.05) of baseline, respectively. However, administration
      of the Na(+)-Ca2+ exchange blockers benzamil (100 or 500 microM) and bepridil (50
      microM) was ineffective. In summary, reduction of extracellular Na+ confers
      neuroprotection after spinal cord injury in vitro. Intracellular sodium rises
      appear to be mediated by voltage-gated Na+ channels. Blockade of the Na(+)-H+
      exchanger also is neuroprotective, possibly by reducing intracellular acidosis.
      Furthermore, prevention of extrusion of intracellular Na+ by the Na(+)-K(+)
      ATPase pump exacerbates the effects of compression trauma. However, reverse
      operation of the Na(+)-Ca2+ exchanger does not explain the injurious effects of
      Na+ in traumatically injured CNS white matter.

PMID- 8551340
TI  - Recovery phase of the murine rod photoresponse reconstructed from
      electroretinographic recordings.
AB  - The activation and recovery phases of the murine rod photo-response were
      determined from corneal electroretinograms (ERGs) obtained in response to pairs
      of full-field flashes producing 50-10(5) photoisomerized rhodopsins (R*) per rod.
      The a-wave component of the ERG in response to the initial flash provided a well
      established measure of the activation phase of the rod response. The amplitude of
      the a-wave response to an intense second flash (45,000 R*) delivered 0.2-5
      seconds (s) after the first flash was used to reconstruct the recovery phase of
      the response. For 160-3000 R* rod-1, recovery curves were isomorphic, translating
      on the time axis such that each e-fold increase in R* produced an incremental
      recovery delay of tau c = 210 +/- 50 ms (mean +/- SD). For initial flashes
      producing > 3000 R*, recovery curves lost their initial isomorphism and half
      times had intensity dependence exceeding 1 s per e-fold increase in R*. We
      conclude that for flashes producing < 3000 R*, the effective lifetime of these R*
      is not > 210 ms. Two extant and non-mutually exclusive hypotheses are discussed
      that can account for the sharp increase in recovery times from flashes producing
      > 3000 R*. They are as follows: (1) approximately 0.03% of R* have a lifetime
      exceeding 1 s; and (2) the gamma subunit of phosphodiesterase (PDE gamma) serves
      as a GTPase-activating factor, and 3000 R* produce sufficient activated G-protein
      (G*) to exceed the total quantity of PDE gamma subunits such that excess G* must
      wait for unoccupied PDE gamma to inactivate via GTP hydrolysis.

PMID- 8551339
TI  - Kinetics of stimulus-coupled secretion in dialyzed bovine chromaffin cells in
      response to trains of depolarizing pulses.
AB  - Stimulus-secretion coupling in bovine chromaffin cells was investigated with
      whole-cell patch-clamp recordings and capacitance detection techniques to monitor
      exocytosis in response to trains of depolarizing pulses. Two kinetically discrete
      modes of exocytotic responses were observed. In one mode, the first
      depolarization of a train elicited a large increase in membrane capacitance (Cm;
      mean approximately 70 fF). This secretory mode was characterized by small Ca2+
      requirements, relative insensitivity to the pipette Ca2+ chelator concentration,
      and rapid depletion of the secretory response. This mode of stimulus-secretion
      coupling was labile and was seen only in response to the first and, occasionally,
      the second stimulus train of whole-cell recordings. The second type of exocytotic
      response persisted for the remainder of the whole-cell recordings and consisted
      of two distinct phases. During the earliest pulses of a stimulus train, Ca2+
      entry did not evoke Cm increases. Instead, Cm responses were elicited by later
      pulses, despite diminished Ca2+ entry per pulse caused by Ca2+ channel
      inactivation. The secretory phase was initiated after a specific "threshold"
      amount of Ca2+ had entered the cell, which was determined by the concentration,
      but not the binding kinetics, of the Ca2+ chelator in the pipette. In both the
      early and the secretory phases, the response of the cell was proportional to
      cumulative Ca2+ entry, regardless of current amplitude, pulse duration, or number
      of pulses. Threshold-type secretory kinetics has been described previously in
      peptide-secreting neurohypophysial (NHP) nerve terminals (Seward et al., 1995).
      Secretory kinetics with minimal Ca2+ requirements has not been observed in that
      preparation. Chromaffin cells appear to possess a broader repertoire of stimulus
      secretion coupling modes than NHP terminals.

PMID- 8551341
TI  - Excitatory actions of norepinephrine on multiple classes of hippocampal CA1
      interneurons.
AB  - Norepinephrine (NE) causes an increase in the frequency of inhibitory
      postsynaptic potentials in CA1 pyramidal neurons in vitro. The possibility that
      this increase in tonic inhibition is caused by an excitatory effect on inhibitory
      interneurons was investigated through whole-cell recordings from pyramidal cells
      and both whole-cell and cell-attached patch recordings from visualized
      interneurons in acute slices of rat hippocampus. Adrenergic agonists caused a
      large increase in the frequency and amplitude of spontaneous IPSCs recorded from
      pyramidal cells in the presence of ionotropic glutamate receptor blockers, but
      they had no effect on either the frequency or the amplitude of action potential
      independent miniature IPSCs recorded in tetrodotoxin. This effect was mediated
      primarily by an alpha adrenoceptor, although a slight beta adrenoceptor-dependent
      increase in IPSCs was also observed. NE caused interneurons located in all strata
      to depolarize and begin firing action potentials. Many of these cells had axons
      that ramified throughout the stratum pyramidale, suggesting that they are
      responsible for the IPSCs observed in pyramidal neurons. This depolarization was
      also mediated by an alpha adrenoceptor and was blocked by a selective alpha 1-
      but not a selective alpha 2-adrenoceptor antagonist. However, a slight beta
      adrenoceptor-dependent depolarization was detected in those interneurons that
      displayed time-dependent inward rectification. In the presence of a beta
      antagonist, NE induced an inward current that reversed near the predicted K+
      equilibrium potential and was not affected by changes in intracellular Cl-
      concentration. In the presence of an alpha 1 antagonist, NE induced an inwardly
      rectifying current at potentials negative to approximately -70 mV that did not
      reverse (between -130 and -60 mV), characteristics similar to the
      hyperpolarization-activated current (lh). However, the depolarizing action of NE
      is attributable primarily to the alpha 1 adrenoceptor-mediated decrease in K+
      conductance and not the beta adrenoceptor-dependent increase in lh. These results
      provide evidence that NE increases action potential-dependent IPSCs in pyramidal
      neurons by depolarizing surrounding inhibitory interneurons. This potent
      excitatory action of NE on multiple classes of hippocampal interneurons may
      contribute to the NE-induced decrease in the spontaneous activity of pyramidal
      neurons and the antiepileptic effects of NE observed in vivo.

PMID- 8551342
TI  - A slowly inactivating potassium current in CA3 pyramidal cells of rat hippocampus
      in vitro.
AB  - The time- and voltage-dependent properties of a slowly inactivating K+ current
      were investigated by using the single-electrode current- and voltage-clamp
      recording technique in CA3 hippocampal cells of organotypic slice cultures. After
      a period of prolonged hyperpolarization, the onset of action-potential discharge
      in response to depolarizing current injection was delayed by several seconds. The
      conductances underlying this delay were identified in voltage-clamp recordings. A
      biphasically decaying outward current was evoked when the membrane potential was
      stepped back to -60 mV after a 30 sec period of hyperpolarization. The fast
      component was identified as the previously described D-current and was blocked by
      100 microM 4-aminopyridine (4-AP). The slow component, which we refer to as
      IK(slow), appeared to be mediated by K+ ions, because its reversal potential
      shifted in a Nernstian manner with changes in extracellular K+ concentration. It
      decayed with a time constant of 7.5 sec and required a hyperpolarizing prepulse
      below -95 mV for 5.5 sec for 50% recovery from inactivation. IK(slow) was found
      to be voltage-dependent, with 50% activation occurring at -65 mV and 50% steady
      state inactivation occurring at -84 mV. It displayed minimal or no sensitivity to
      the K(+)-channel blockers 4-AP (0.1-5 mM), Cs+ (1 mM), tetraethylammonium (10-50
      mM), Ba2+ (1 mM), dendrotoxin-alpha (5-10 microM), charybdotoxin (0.5-2.5
      microM), or glibenclamide (5-10 microM) and was not affected by preventing
      increases in intracellular Ca2+ concentration with Ca2+ chelators. IK(slow) was
      reduced by activation of metabotropic glutamatergic and cholinergic receptors. In
      summary, the biophysical characteristics of IK(slow) suggest a role in
      determining discharge onset after a period of membrane hyperpolarization, and its
      modulation by G-protein-coupled receptors reveals an additional function for
      these receptors in the control of cellular excitability.

PMID- 8551343
TI  - Estradiol reduces calcium currents in rat neostriatal neurons via a membrane
      receptor.
AB  - Until recently, steroid hormones were believed to act only on cells containing
      intracellular receptors. However, recent evidence suggests that steroids have
      specific and rapid effects at the cellular membrane. Using whole-cell patch-clamp
      techniques, 17 beta-estradiol was found to reduce Ba2+ entry reversibly via Ca2+
      channels in acutely dissociated and cultured neostriatal neurons. The effects
      were sex-specific, i.e., the reduction of Ba2+ currents was greater in neurons
      taken from female rats. 17 beta-Estradiol primarily targeted L-type currents, and
      their inhibition was detected reliably within seconds of administration. The
      maximum reduction by 17 beta-estradiol occurred at picomolar concentrations. 17
      beta-Estradiol conjugated to bovine serum albumin also reduced Ba2+ currents,
      suggesting that the effect occurs at the membrane surface. Dialysis with GTP
      gamma S prevented reversal of the modulation, suggesting that 17 beta-estradiol
      acts via G-protein activation. 17 alpha-Estradiol also reduced Ba2+ currents but
      was significantly less effective than 17 beta-estradiol. Estriol and 4
      hydroxyestradiol were found to reduce Ba2+ currents with similar efficacy to 17
      beta-estradiol, whereas estrone and 2-methoxyestriol were less effective.
      Tamoxifen also reduced Ba2+ currents but did not occlude the effect of 17 beta
      estradiol. These results suggest that at physiological concentrations, 17 beta
      estradiol can have immediate actions on neostriatal neurons via nongenomic
      signaling pathways.

PMID- 8551344
TI  - The role of adenosine A2a receptors in regulating GABAergic synaptic transmission
      in striatal medium spiny neurons.
AB  - We demonstrated an adenosine A2a receptor-mediated disinhibition of medium spiny
      projection neurons using intracellular recording and the whole-cell patch-clamp
      recording applied to these cells, visually identified in thin rat striatal
      slices. The A2a receptor agonist 2-[p-(2-carboxyethyl) phenylethylamino]-5'-N-
      ethylcarboxamido adenosine (CGS-21680; 0.3-10 microM) suppressed GABAergic
      synaptic transmission onto these cells in a manner inhibited by the A2a receptor
      selective antagonist (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine
      (0.1-1.0 microM). The A1 receptor antagonists had no effect on the CGS-21680
      induced suppression. Analysis of spontaneous miniature inhibitory synaptic
      currents indicated that suppression of intrastriatal GABAergic synaptic
      transmission was attributable to presynaptic, but not postsynaptic, A2a
      receptors. Therefore, the A2a receptor may regulate striatal output activity by
      relieving GABA-mediated inhibition of the medium spiny projection neurons, which
      explains the ability of purinergic agents to affect motor control.

PMID- 8551345
TI  - Specificity of sympathetic preganglionic projections in the chick is influenced
      by the somitic mesoderm.
AB  - It has been shown that the development of segmentally specific sympathetic
      preganglionic projections in the chick is influenced by the tissue environment
      along the pathway of the preganglionic axons. The cellular origin of this
      influence, however, is not known. In the present study, transplantation of quail
      somites into chick hosts showed that the cells in the local environment of the
      sympathetic trunk are derived from the somite. Surgical manipulations of chick
      somites then were performed to investigate whether somites play a role in the
      establishment of preganglionic projection patterns. When cervical somites were
      transplanted to the thoracic region, preganglionic neurons adjacent to the
      transplanted somites projected aberrantly. In addition, when somites were
      removed, the pattern of preganglionic axonal projections to their target ganglia
      was altered. These results indicate that the specificity of sympathetic
      preganglionic projections is influenced by the somitic mesoderm.

PMID- 8551346
TI  - Immunohistochemical localization of ciliary neurotrophic factor receptor alpha
      expression in the rat nervous system.
AB  - Ciliary neurotrophic factor receptor alpha (CNTFR alpha) is essential for normal
      embryonic development and may be involved in postnatal and adult neuronal
      maintenance. In addition, a rapidly growing body of evidence suggests that CNTFR
      alpha serves as a site of action for future growth factor therapeutics capable of
      treating a wide variety of disorders resulting from neuronal loss. We raised two
      polyclonal, anti-CNTFR alpha antisera against synthetic peptides corresponding to
      independent regions of rat CNTFR alpha. Western blot and immunohistochemical
      analyses indicated that affinity-purified preparations of both antisera
      specifically recognize CNTFR alpha. In the adult brain, the highest levels of
      CNTFR alpha immunoreactivity were found in the perikarya, dendrites and,
      occasionally, the axons of several distinct classes of neurons including
      hippocampal formation neurons, some sensory neurons, and many neurons involved in
      motor control. CNTFR alpha immunoreactivity also was concentrated in the
      following: perikarya, dendrites, and axons of ventral horn motor neurons in adult
      spinal cord; perikarya and axons of adult dorsal root ganglion neurons; and axons
      in adult peripheral nerve. In embryonic tissue, the highest levels of CNTFR alpha
      immunoreactivity were observed in differentiating neurons and their processes.
      Therefore, the present data suggest that CNTFR alpha serves several diverse
      functions in adulthood and during development.

PMID- 8551347
TI  - Neuronal activity differentially regulates NMDA receptor subunit expression in
      cerebellar granule cells.
AB  - Reverse-transcription PCR assays were used to measure levels of NMDA receptor
      (NR) subunit mRNAs encoding splice variants of NR1 (NR1a, -exon 5; NR1b, +exon 5)
      and the major NR2 subunits (NR2A, NR2B, and NR2C) in dissociated cerebellar
      granule cell cultures. Cultures chronically exposed to 25 mM KCl or 100 microM
      NMDA/15 mM KCl, which promote survival by stimulating Ca2+ influx through voltage
      sensitive Ca2+ channels or NRs, were compared with 5 mM KCl culture conditions,
      which results in limited cell survival attributable to a lower level of NR
      stimulation by ambient glutamate. In situ granule-cell maturation is associated
      with downregulation of NR2B and increases both of NR2A and NR2C and in the ratio
      of NR1b/NR1a mRNAs. In culture, 25 mM KCl or NMDA rapidly induced NR2A and
      downregulated NR2B, followed by gradual induction of NR2C. In 5 mM KCl, a
      similar, rapid increase in NR2A was observed, but disappearance of NR2B occurred
      over a longer time course. By 9-12 d in vitro in 5 mM KCl, the relative
      proportions of all three NR2 mRNAs in surviving cells were not significantly
      different from cells cultured in 25 mM KCl. NR1a mRNA predominated at every stage
      of culture in 25 mM KCl or NMDA, however, whereas gradual induction of the mature
      form NR1b was observed in 5 mM KCl. Although using high potassium- or NMDA
      containing media enhanced granule cell survival, it did not reproduce the pattern
      of expression of NR mRNAs observed in situ, whereas this pattern was observed in
      granule cells surviving in 5 mM KCl.

PMID- 8551348
TI  - Selective failure of brain-derived neurotrophic factor mRNA expression in the
      cerebellum of stargazer, a mutant mouse with ataxia.
AB  - In search of the possible involvement of neurotrophic factors in inherited
      neurological disease, we examined brain-derived neurotrophic factor (BDNF), nerve
      growth factor (NGF), and neurotrophin-3 (NT-3) mRNA expression patterns in the
      ataxic mutant mouse stargazer (stg). Using in situ hybridization, we found a
      selective and near total reduction in BDNF mRNA in the cerebellar granule cell
      layer. NT-3 or NGF mRNA expression in the cerebellum was normal. Northern blot
      analysis demonstrated a 70% reduction in BDNF mRNA in the whole cerebellum. BDNF
      mRNA levels in other mutant brain regions were unchanged. Absence of BDNF mRNA in
      granule cells was observed at postnatal age (P15), coincident with the onset of
      ataxia, and expression levels failed to follow the developmental increase found
      in the wild type at later ages (P20 and P30). Despite the severe BDNF reduction,
      in situ hybridization patterns for both the full-length and the truncated BDNF
      TrkB receptor mRNA were unaltered. No major cytoarchitectural abnormalities were
      apparent in the stg/stg cerebellum. BDNF expression in a related ataxic mutant,
      tottering, was unaltered. These data show that BDNF can be regulated selectively
      in distinct brain regions, possibly by differential activation of its multiple
      promoters. Absence of cerebellar granule cell BDNF mRNA in stg/stg mice
      demonstrates that sustained expression of this neurotrophin is not required for
      cell survival in the developing cerebellar cortex. Our data, in contrast, suggest
      a role of BDNF in maturation of specific cerebellar neurons and pathways. Early
      failure of cerebellar BDNF expression may be related to the ataxic phenotype in
      stg mice.

PMID- 8551349
TI  - Regeneration of sensory cells after laser ablation in the lateral line system:
      hair cell lineage and macrophage behavior revealed by time-lapse video
      microscopy.
AB  - The regeneration of sensory hair cells in lateral line neuromasts of axolotls was
      investigated via nearly continuous time-lapse microscopic observation after all
      preexisting hair cells were killed by a laser microbeam. The laser treatments
      left neuromasts with one resident cell type, which was supporting cells. Over the
      course of 1 week, replacement hair cells arose either directly via
      differentiation of cells present in the epithelium from the beginning of the time
      lapse period or via the development of cells produced after one or two divisions
      of supporting cells. All of the cell divisions that produced hair cells were
      asymmetrical. During the first hour after the treatment, macrophages and smaller
      leukocytes were attracted to the laser-treated neuromasts. The smaller leukocytes
      returned to control levels 48-60 hr after the treatment, whereas macrophages
      remained active there throughout the period of hair cell replacement. Macrophage
      incidence peaked 36-48 hr after the laser treatment. Macrophages phagocytosed
      damaged hair cells and supporting cells, as well as new cells and preexisting
      cells without recognizable damage. The results provide direct evidence of hair
      cells arising as progeny produced from the divisions of supporting cells,
      evidence of hair cells and supporting cells arising from the same cell division,
      evidence relating to the timing of hair cell differentiation, and indirect
      evidence pertaining to proposals that hair cells sometimes arise via conversion
      of cells without an intervening division. The results also suggest that
      macrophages may influence early stages in the process of hair cell regeneration.

PMID- 8551350
TI  - Developmental expression and biochemical analysis of conulin, a protein secreted
      from a subset of neuronal growth cones.
AB  - In this report, we analyze the developmental pattern of expression of a new
      grasshopper protein, Conulin, using the monoclonal antibody 7D2 on whole-mount
      embryos and dissociated neurons. We also have examined its biochemical properties
      by immunoblot analysis. Conulin is a protein expressed by a subset of neurons in
      the grasshopper embryo. The monoclonal antibody 7D2 recognizes Conulin as an M(r)
      190 x 10(3) protein that is found in both the soluble and membrane-bound
      fractions of embryonic proteins. The membrane association is disrupted by
      alkaline pH and high ionic strength. Conulin first is expressed and stored in
      vesicles inside the cell bodies and axons of central and peripheral neurons.
      Later, Conulin is detected on the cell surface, but exclusively in the central
      nervous system neuropil. This expression is confined to a subset of nerve growth
      cones. Conulin is detected on growth cones only after pioneer neurons have
      outlined the axonal scaffold. Immunocytochemistry on cultured embryonic neurons
      demonstrates that the neurons have the autonomous ability to target Conulin to
      the growth cones. The protein is secreted but remains transiently associated with
      the growth cone plasma membrane. The discovery of Conulin confirms the existence
      of proteins specific for the nerve growth cone. Its transitory presence during
      axonogenesis in only a subset of follower growth cones suggests that Conulin is
      involved in guidance through selective fasciculation with pre-existing axons
      within the ganglionic neuropil.

PMID- 8551351
TI  - Brain-derived neurotrophic factor promotes the differentiation of various
      hippocampal nonpyramidal neurons, including Cajal-Retzius cells, in organotypic
      slice cultures.
AB  - Brain-derived neurotrophic factor (BDNF) is widely expressed in the central
      nervous system, where its function is poorly understood. The aim of this study
      was to investigate the effects of BDNF on the differentiation of hippocampal
      nonpyramidal neurons using organotypic slice cultures prepared from postnatal
      rats. The application of BDNF induced an increase in immunostaining for the
      microtubule-associated protein (MAP)-2 in non-pyramidal neurons of the stratum
      oriens. BDNF promotes the elongation of the dendrites of these neurons, as
      demonstrated by analysis after biocytin labeling. Calbindin-D- and calretinin
      containing subgroups of nonpyramidal cells in the stratum oriens were responsive
      to BDNF but not to nerve growth factor, as shown by an increase in the number of
      neurons immunostained for these proteins. BDNF also induced an increase in
      neuropeptide Y immunostaining of stratum oriens neurons. In contrast, BDNF had no
      effect on parvalbumin immunostaining, despite the fact that these cells express
      the BDNF receptor trkB. In addition, BDNF increased calretinin immunoreactivity
      in Cajal-Retzius cells situated around the hippocampal fissure. The Cajal-Retzius
      neurons persisted in slices beyond the time at which they degenerate in vivo.
      However, BDNF is not required for the survival of these cells, because they also
      persisted in slices from BDNF knock-out mice. The present results indicate that
      BDNF exerts an effect on the morphology of stratum oriens nonpyramidal cells and
      their calcium-binding protein levels. BDNF also regulates the calretinin content
      of Cajal-Retzius cells but is not necessary for their survival.

PMID- 8551352
TI  - Identification and molecular characterization of Unc-33-like phosphoprotein
      (Ulip), a putative mammalian homolog of the axonal guidance-associated unc-33
      gene product.
AB  - The control of neuritic extension and guidance is critical for the development,
      maturation, and regeneration of functional neuronal circuits. We identified a
      neuronal 64-85 kDa phosphoprotein, the expression of which in mouse brain is
      regulated during development, reaching a peak at approximately 5 d postnatal,
      when maturation of neurons and synaptic connections is highly active. The amino
      acid sequence of the mouse protein deduced from its cloned cDNA reveals
      similarities with that of the neuritic outgrowth- and guidance-related product of
      the unc-33 gene in Caenorhabditis elegans. The regulation of its phosphorylation
      in response to nerve growth factor, as well as its localization in neurites and
      growth cones and at the neuromuscular junction, further indicates that Ulip (for
      Unc-33-like phosphoprotein) is not only a structural but likely is also a
      functional mammalian homolog of Unc-33, potentially involved in the control of
      neuritic outgrowth and axonal guidance.

PMID- 8551353
TI  - Cell-specific differential expression of Na(+)-channel beta 1-subunit mRNA in the
      olfactory system during postnatal development and after denervation.
AB  - Activity-dependent mechanisms have been implicated in olfactory system
      development but, although such activity requires ion channels, few reports have
      described their expression in the olfactory system. We investigated the
      developmental and denervation-induced regulation of the Na(+)-channel beta 1
      subunit (Na beta 1) in rat olfactory bulb (OB) and piriform cortex (PC). In situ
      hybridization shows that Na beta 1 mRNA expression is upregulated
      developmentally, but with different time courses in mitral, tufted, and pyramidal
      cells. In mitral cells, label was detected at postnatal day 4 (P4) and gradually
      increased to P14. Tufted cells were devoid of Na beta 1 mRNA before P14, when
      most cells expressed adult levels. In pyramidal cells of PC, Na beta 1 expression
      was not detectable clearly until P14, with maximal expression at P28. To examine
      the regulation of Na beta 1 mRNA, we surgically deafferented the OB at P30 and
      compared the effects on Na beta 1 with those for Na(+)-channel alpha-subunit (Na
      alpha) mRNAs. Within 5 d of surgery, the Na beta 1 and Na alpha II signals within
      tufted cells disappeared almost completely. Na beta 1 and Na alpha II expression
      was decreased in mitral cells to low-to-moderate levels. In pyramidal cells, Na
      beta 1 mRNA expression was decreased moderately without significant changes in Na
      alpha II mRNA. Deafferentation had no detectable effects on Na alpha I or III
      mRNAs in either OB or PC. These data indicate that Na beta 1 mRNA is expressed
      differentially in subpopulations of cells in the olfactory system during
      development and after deafferentation and suggest that the expression of Na beta
      1 is regulated independently of Na alpha mRNAs via cell-specific and pathway
      specific mechanisms.

PMID- 8551354
TI  - Modulation of dopamine efflux in the nucleus accumbens after cholinergic
      stimulation of the ventral tegmental area in intact, pedunculopontine tegmental
      nucleus-lesioned, and laterodorsal tegmental nucleus-lesioned rats.
AB  - Microinjections of the cholinergic receptor agonist nicotine and the
      cholinesterase inhibitor neostigmine were made into the ventral tegmental area
      (VTA) of urethane-anesthetized rats, and dopamine (DA) efflux in the nucleus
      accumbens was measured using in vivo chronoamperometry. Dose-dependent increases
      in the chronoamperometric signals corresponding to increased DA efflux were
      observed in the nucleus accumbens of normal intact rats after cholinergic
      stimulation of the VTA. The source of the cholinergic input to the VTA was
      investigated by making excitotoxic lesions in either the laterodorsal tegmental
      nucleus (LDTg) or the pedunculopontine tegmental nucleus (PPTg). Compared with
      sham-operated control animals, which showed the same response as intact,
      nonlesioned rats, ibotenate lesions of the LDTg attenuated the stimulatory
      effects of intra-VTA neostigmine on DA efflux in the nucleus accumbens. In
      contrast, rats with ibotenate lesions of the PPTg showed normal nucleus accumbens
      DA eflux after intra-VTA injections of neostigmine. Such lesions in the PPTg
      attenuate DA efflux in the caudate-putamen stimulated by injections of
      neostigmine into the substantia nigra pars compacta (SNc). The present data show
      that cholinergic neurons in the LDTg, but not the PPTg, regulate the activity of
      DA-containing neurons in the VTA, which complements previous data showing that
      cholinergic neurons in the PPTg regulate DA-containing neurons in the SNc.

PMID- 8551355
TI  - Characterization of a descending system that enables crossed group II inhibitory
      reflex pathways in the cat spinal cord.
AB  - In the cat, stimulation of group II afferents from hindlimb muscles evokes
      different crossed reflex actions depending on the integrity of the spinal cord:
      with the cord intact, extensor motoneurons are inhibited by activation of
      contralateral group II afferents; after spinal transection, the same stimuli
      excite these neurons (crossed extension reflex). We have investigated the
      mechanisms underlying this descending control. To delimit the descending pathway,
      the effects of funicular lesions of the thoracic cord on the crossed actions on
      motoneurons were examined. Bilateral lesions of the dorsolateral funiculi
      abolished the crossed IPSPs as effectively as complete spinal section. If either
      dorsolateral funiculus was spared, the IPSPs remained. To examine whether
      serotonergic fibers were involved, the effects of agents selective for 5
      hydroxytryptamine (5-HT)1A receptors were examined. After abolishing the crossed
      IPSPs by spinal transection, systemic administration of the 5-HT1A receptor
      agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 0.1
      1.3 mg/kg, i.v.) restored the crossed inhibition. This effect was antagonized by
      the selective 5-HT1A receptor antagonist WAY-100135 (0.7-3.7 mg/kg, i.v.). The
      simplest explanation of these findings is that a serotonergic pathway, descending
      via the dorsolateral funiculi and acting via 5-HT1A receptors, is involved: with
      the spinal cord intact, the pathway would be tonically active and thus enable the
      crossed inhibition. This raises the possibility that a serotonergic pathway is
      involved in the selection of specific spinal reflex patterns via 5-HT1A
      receptors.

PMID- 8551356
TI  - Spinal cord NMDA receptors modulate peripheral immune responses and spinal cord c
      fos expression after immune challenge in rats subjected to unilateral
      mononeuropathy.
AB  - To characterize further the neural involvement in local immune reactions, we
      evaluated the effect of intrathecal NMDA-receptor blocker dizocilpine maleate (MK
      801) on the peripheral immune response itself and on spinal cord c-fos expression
      induced by the delayed-type hypersensitivity (DTH) response. Immune challenge
      took place in the hind paw ipsilateral or contralateral to an injured sciatic
      nerve in both previously sensitized and immune-naive animals. An enhanced immune
      response was observed bilaterally in the hind paws of animals subjected to
      unilateral mononeuropathy compared with sham-operated controls. In contrast, no
      such enhancement was observed when neuropathic animals were challenged in the
      front paws. The increased DTH response was blocked successfully by the
      intrathecal administration of an analgesic dose of MK-801. Compared with sham
      operated animals, animals subjected to unilateral mononeuropathy showed both a
      differential distribution and an increase in the number of c-fos-labeled neurons
      in the dorsal horn of the L3-L5 spinal cord segments after immune challenge. This
      was observed irrespective of whether the challenge took place ipsilateral or
      contralateral to the injured nerve. In addition to reversing the changes in
      immune response, intrathecal administration of MK-801 reversed the pattern of c
      fos immunoreactivity in the spinal cord after immune challenge in neuropathic
      animals. These data suggest that select groups of spinal cord neurons participate
      in enhancing the peripheral immune response to a specific antigen in neuropathic
      animals and that this enhancement involves central NMDA receptors.

PMID- 8551357
TI  - Cholinergic regulation of the suprachiasmatic nucleus circadian rhythm via a
      muscarinic mechanism at night.
AB  - In mammals, the suprachiasmatic nucleus (SCN) is responsible for the generation
      of most circadian rhythms and for their entrainment to environmental cues.
      Carbachol, an agonist of acetylcholine (ACh), has been shown to shift the phase
      of circadian rhythms in rodents when injected intracerebroventricularly. However,
      the site and receptor type mediating this action have been unknown. In the
      present experiments, we used the hypothalamic brain-slice technique to study the
      regulation of the SCN circadian rhythm of neuronal firing rate by cholinergic
      agonists and to identify the receptor subtypes involved. We found that the phase
      of the oscillation in SCN neuronal activity was reset by a 5 min treatment with a
      carbachol microdrop (1 microliter, 100 microM), but only when applied during the
      subjective night, with the largest phase shift (+ 6 hr) elicited during the
      middle of the subjective night. This effect also was produced by ACh and two
      muscarinic receptor (mAChR) agonists, muscarine and McN-A-343 (M1-selective), but
      not by nicotine. Furthermore, the effect of carbachol was blocked by the mAChR
      antagonist atropine (0.1 microM), not by two nicotinic antagonists, dihydro-beta
      erythroidine (10 microM) and d-tubocurarine (10 microM). The M1-selective mAChR
      antagonist pirenzepine completely blocked the carbachol effect at 1 microM,
      whereas an M3-selective antagonist, 4,2-(4,4'-diacetoxydiphenylmethyl)pyridine,
      partially blocked the effect at the same concentration. These results demonstrate
      that carbachol acts directly on the SCN to reset the phase of its firing rhythm
      during the subjective night via an M1-like mAChR.

PMID- 8551358
TI  - Simultaneously recorded single units in the frontal cortex go through sequences
      of discrete and stable states in monkeys performing a delayed localization task.
AB  - To test whether spiking activity of six to eight simultaneously recorded neurons
      in the frontal cortex of a monkey can be characterized by a sequence of discrete
      and stable states, neuronal activity is analyzed by a hidden Markov model (HMM).
      Using the HMM method, we are able to detect distinct states of neuronal activity
      within which firing rates are approximately stationary. Transitions between
      states, as expressed by concomitant changes in the firing rates of several units,
      occur quite abruptly. The significance and consistency of the states are
      confirmed by comparison with simulated data. The detected states are specific to
      a monkey's response in a delayed localization task, allowing correct prediction
      of the response in approximately 90% of the trials. Similar predictive power is
      achieved by a model based simply on the response histograms (PSTH) of the units.
      The two models reach this predictive ability with different time courses: the
      PSTH model gains predictive power with a higher rate in the first second of the
      delay, and the HMM gains predictive power with higher rate in the next 3 sec. In
      this later period, conventional methods such as the PSTH cannot detect any firing
      rate modulations, but the HMM successfully captures transitions between distinct
      states that are specific to the monkey's behavioral response and occur at highly
      variable times from trial to trial. Our results suggest that neuronal activity in
      this later period is described best as transitions among distinct states that may
      reflect discrete steps in the monkey's mental processes.

PMID- 8551359
TI  - Functional organization of a neural map in the cricket cercal sensory system.
AB  - Directionally selective mechanosensory afferents in the cricket cercal sensory
      system form a map of air current direction in the terminal abdominal ganglion.
      The global organization of this map was revealed by studying the anatomical
      relationships between an ensemble of sensory afferents that represented the
      entire range of receptor hair directional sensitivities on the sensory
      epithelium. The shapes and three-dimensional positions of the terminal
      arborizations of these cells were highly conserved across animals. Afferents with
      similar directional sensitivities arborized near each other within the map, and
      their terminal arborizations showed significant anatomical overlap. There was a
      clear global organization pattern of afferents within the map: they were
      organized into a spiral shape, with stimulus direction mapped continuously around
      the spiral. These results demonstrate that this map is not formed via a direct
      point-to-point topographic projection from the sensory epithelium to the CNS.
      Rather, the continuous representation of air current direction is synthesized
      within the CNS via an anatomical reorganization of the afferent terminal arbors.
      The arbors are reorganized according to a functional property that is independent
      of the location of the mechanoreceptor in the epithelium. The ensemble data were
      used to derive predictions of the patterns of steady-state excitation throughout
      the map for different directional stimuli. These images represent quantitative
      and testable predictions of functional characteristics of the entire neural map.

PMID- 8551360
TI  - Use-dependent alterations of movement representations in primary motor cortex of
      adult squirrel monkeys.
AB  - This study was undertaken to document plastic changes in the functional
      topography of primary motor cortex (M1) that are generated in motor skill
      learning in the normal, intact primate. Intracortical microstimulation mapping
      techniques were used to derive detailed maps of the representation of movements
      in the distal forelimb zone of M1 of squirrel monkeys, before and after
      behavioral training on two different tasks that differentially encouraged
      specific sets of forelimb movements. After training on a small-object retrieval
      task, which required skilled use of the digits, their evoked-movement digit
      representations expanded, whereas their evoked-movement wrist/forearm
      representational zones contracted. These changes were progressive and reversible.
      In a second motor skill exercise, a monkey pronated and supinated the forearm in
      a key (eyebolt)-turning task. In this case, the representation of the forearm
      expanded, whereas the digit representational zones contracted. These results show
      that M1 is alterable by use throughout the life of an animal. These studies also
      revealed that after digit training there was an areal expansion of dual-response
      representations, that is, cortical sectors over which stimulation produced
      movements about two or more joints. Movement combinations that were used more
      frequently after training were selectively magnified in their cortical
      representations. This close correspondence between changes in behavioral
      performance and electrophysiologically defined motor representations indicates
      that a neurophysiological correlate of a motor skill resides in M1 for at least
      several days after acquisition. The finding that cocontracting muscles in the
      behavior come to be represented together in the cortex argues that, as in sensory
      cortices, temporal correlations drive emergent changes in distributed motor
      cortex representations.

PMID- 8551361
TI  - A positron emission tomography study of the short-term maintenance of verbal
      information.
AB  - Positron emission tomography (PET) was used to investigate the functional brain
      anatomy associated with the short-term maintenance of linguistic information.
      Subjects were asked to retain five related words, unrelated words, or pseudowords
      silently for the duration of a 40 sec PET scan. When brain activity during these
      short-term maintenance tasks was compared with a visual fixation control task,
      increases were found bilaterally in the dorsolateral prefrontal cortex and
      cerebellum, and medially in the supplementary motor area. Furthermore, effects of
      stimulus condition and recall performance were found in the left frontal
      operculum. To investigate the role of articulatory systems in the maintenance of
      verbal information, regional activation was compared across the maintenance tasks
      and a covert articulation task (silent counting). The cerebellum was active in
      both task conditions, whereas activation in prefrontal regions was specific to
      the maintenance condition. Conversely, greater activation was found in a left
      middle insular region in the silent counting than in the maintenance tasks. Based
      on converging results in this and previous studies, dorsolateral prefrontal
      cortical areas appear to contribute to the maintenance of both verbal and
      nonverbal information, whereas left frontal opercular regions appear to be
      involved specifically in the rehearsal of verbal material. Contrary to results
      found in other studies of working memory, activation was not found in the
      inferior parietal cortex, suggesting that this area is involved in aspects of
      stimulus encoding and retrieval, which were minimized in the present study.

PMID- 8551362
TI  - Binding of hippocampal CA1 neural activity to multiple reference frames in a
      landmark-based navigation task.
AB  - The behavioral correlates of rat hippocampal CA1 cells were examined in a spatial
      navigation task in which two cylindrical landmarks predicted the location of
      food. The landmarks were maintained at a constant distance from each other but
      were moved from trial to trial within a large arena surrounded by static
      background cues. On each trial, the rats were released from a box to which they
      returned for additional food after locating the goal. The box also was located
      variably from trial to trial and was moved to a new location while the animals
      were searching for the goal site. The discharge characteristics of multiple,
      simultaneously recorded cells were examined with respect to the landmarks, the
      static background cues, and the box in which each trial started and ended. Three
      clear categories of cells were observed: (1) cells with location-specific firing
      (place cells); (2) goal/landmark-related cells that fired in the vicinity of the
      goal or landmarks, regardless of their location in the arena; and (3) box-related
      cells that fired either when the rat was in the box or as it was leaving or
      entering the box, regardless of its location in the arena. Disjunctive cells with
      separate firing fields in more than one reference frame also were observed. These
      results suggest that in this task a subpopulation of hippocampal cells encodes
      location in the fixed spatial frame, whereas other subpopulations encode location
      with respect to different reference frames associated with the task-relevant,
      mobile objects.

PMID- 8551363
TI  - Neonatal deprivation of maternal touch may suppress ornithine decarboxylase via
      downregulation of the proto-oncogenes c-myc and max.
AB  - Previously, we have shown that short-term (1 hr) separation of neonatal rats from
      their mother (MS) suppresses basal ornithine decarboxylase (ODC) synthesis and
      tissue ODC response to trophic factors. This effect in the pup is caused by
      absence of maternal tactile stimulation (touch) but not from lack of maternal
      nutrients (food). This study was performed to examine in 10-d-old rats whether
      maternal touch deprivation affects expression of certain hepatic proto-oncogenes,
      the protein products of which are known to interact with the regulatory region of
      the ODC gene. Prolactin (PRL) injected subcutaneously increased hepatic ODC
      activity as well as mRNA levels of ODC and the proto-oncogenes c-fos, c-jun,
      junB, junD, c-myc, and max. MS significantly suppressed PRL-induced increases in
      ODC enzyme activity and c-myc, max, and ODC mRNAs but had little effect on
      expression of the other proto-oncogenes. PRL-induced stimulation of ODC, c-myc,
      and max mRNAs also was depressed in neonates placed with an anesthetized
      lactating dam (touch-deprived) but not in pups placed with nipple-ligated dams
      (food-deprived). Furthermore, unlike its effect on preweanling-age pups (< 20 d
      old), MS did not alter expression of either ODC or c-myc mRNAs in 25-d-old pups
      acutely separated from their mother. These findings indicate that suppression of
      ODC gene transcription in the neonatal pup during MS may be mediated by
      downregulation of the ODC gene transactivator proto-oncogenes c-myc and max. They
      are also consistent with our previous observation that lack of maternal touch,
      but not maternal milk, initiates the physiological alterations induced by MS.

PMID- 8551364
TI  - Interactions between the neural networks for escape and swimming in goldfish.
AB  - Interactions between neural networks for different motor behaviors occur
      frequently in nature; however, there are few vertebrate models for studying these
      interactions. One potentially useful model involves the interactions between
      escape and swimming behaviors in fish. Fish can produce escape bends while
      swimming, using some of the same axial muscles for both behaviors. Here we study
      the interactions between escape and swimming in a paralyzed goldfish preparation
      in which we can activate the networks for both behaviors. Fictive swimming was
      elicited by electrical stimulation in the midbrain locomotor region. During the
      swimming, we fired a single action potential in the reticulospinal Mauthner (M)
      cell, which initiates the escape behavior (Zottoli, 1977). Firing the M cell
      overrode the swimming motor output to produce an output appropriate for escape
      regardless of the phase of swimming at which it was fired. The M cell also could
      reset the swimming rhythm dramatically in a way that led to a smooth transition
      from an escape bend to one side into subsequent swimming. Both the override and
      reset supported predictions based on previous studies of the organization of the
      M-cell network. They apparently allow for a well coordinated motor output when a
      fish must produce an escape while swimming. The potent effects of one action
      potential in a single, identifiable reticulospinal neuron make this an attractive
      model system for future studies of the cellular basis of interactions between
      descending pathways and spinal rhythm-generating networks.

PMID- 8551365
TI  - Factors regulating the reversibility of long-term potentiation.
AB  - Theta burst stimulation (TBS) produces an extremely stable form of long-term
      potentiation (LTP). In contrast, a brief episode of single-pulse stimulation at
      theta frequency [theta pulse stimulation (TPS)] has been demonstrated to reverse
      LTP in area CA1 of slices and freely moving animals without causing depression
      when administered to nonpotentiated pathways. The present in vitro studies
      confirm these results and establish that the susceptibility of LTP to reversal
      and the degree of depotentiation are time-dependent. Specifically, a 1 min train
      of TPS delivered 30 sec after LTP induction produced an almost complete and
      lasting depotentiation but had increasingly less impact at longer delays and
      virtually no effect at 30 min. Increasing the duration of TPS did not cause more
      depotentiation. However, pharmacological facilitation of AMPA receptor-mediated
      currents significantly enhanced the strength of the reversal process and allowed
      TPS to produce robust depotentiation up to 30 min after LTP induction. The
      reversal effect was selective to potentiated synapses receiving TPS, was
      reversible, and was not blocked by NMDA receptor antagonism. Additional
      experiments indicated that AMPA receptor facilitation promotes depotentiation by
      enhancing an active process triggered by TPS that reverses expression without
      extending the time course of consolidation. These results suggest that the
      mechanisms responsible for LTP reversal are linked to the amplitude and/or
      duration of fast excitatory currents mediated by synaptic AMPA receptors and are
      effective up to the completion of LTP stabilization.

PMID- 8551366
TI  - Receptive-field plasticity in the adult auditory cortex induced by Hebbian
      covariance.
AB  - The goal of this experiment was to evaluate the role of cellular interactions
      postulated by the Hebbian, or covariance, hypothesis in the induction of
      receptive-field (RF) plasticity in the adult auditory cortex (ACx). This was
      accomplished by determining whether a "covariance treatment" (see below) was
      sufficient to induce RF plasticity without behavioral experiences that normally
      induce such plasticity. During the covariance treatment (conducted in urethane
      anesthetized adult guinea pigs), one tone was paired with excitatory
      juxtacellular current, applied to a single postsynaptic cell in the primary ACx.
      Excitatory current increased postsynaptic discharge, thereby increasing
      covariance between activity of the postsynaptic cell and its afferents that were
      activated by the tone. In alternation, within the same cell a second, different
      tone was paired with inhibitory juxtacellular current, decreasing covariance
      between the postsynaptic cell and afferents activated by the second tone. After
      treatment, responses to tones associated with increased covariance strengthened
      significantly relative to tones associated with decreased covariance, as
      predicted by the Hebbian hypothesis. This occurred in 7 of 22 (32%) cells
      undergoing 120 pairing trials, but in only 4 of 38 (11%) cells undergoing 60
      trials. Fewer than 5% of cells showed significant effects opposite those
      predicted by the hypothesis. Significant plasticity lasted > or = 15 min.
      Probability of plasticity was significantly higher when the cortical
      electroencephalogram was nonsynchronized during treatment (5/9 cells) than when
      synchronized (2/13 cells). These findings support the role of presynaptic
      postsynaptic covariance processes in the induction of adult neocortical RF
      plasticity and suggest that factors associated with cortical state "gate" such
      plasticity.

PMID- 8551367
TI  - Follow-up home care.

PMID- 8551368
TI  - Development and implementation of a perinatal education consortium.
AB  - The North Puget Sound Perinatal Education Consortium provides a collaborative
      framework for planning, implementing, and evaluating a basic orientation program
      for newly hired and cross-trained perinatal nurses. The program currently
      provides 9 days of prenatal, labor and delivery, mother-infant couplet, and
      neonatal didactic orientation at no cost to registrants from participating
      hospitals. Consortium hospitals supply instruction time and additional services
      to support this high-quality, regional, perinatal orientation program.

PMID- 8551369
TI  - Adolescent parenting: outcomes and maternal perceptions.
AB  - OBJECTIVE: To describe selected outcomes and maternal perceptions of adolescent
      parenting. DESIGN: Qualitative and quantitative methods, interview, and two
      standardized instruments were combined in this follow-up study of adolescents who
      received perinatal services between 1985 and 1988. SETTING: Data were collected
      in the mothers' homes. PARTICIPANTS: Mothers who were randomly selected for an
      earlier chart outcome audit (N = 98) and could be located (n = 19). MAIN OUTCOME
      MEASURES: Subsequent pregnancies; school completion; children's development,
      indicated by the Developmental Profile II (DPII); parental attitudes, indicated
      by the Adult-Adolescent Parenting Inventory (AAPI); and maternal perceptions.
      RESULTS: Responses revealed irregular use of contraceptives as one reason for the
      initial pregnancy and for subsequent unplanned pregnancies. Sixteen mothers
      completed high school, and 18 intend to complete postsecondary programs. The DPII
      indicated age-appropriate development of the children. AAPI scores for 84% of the
      mothers indicated nonnurturing attitudes. Mothers described family support,
      motherhood, and their children. CONCLUSIONS: Research is needed with larger
      samples and to test interventions to promote regular use of contraception.
      Findings support the need for research-based programs to educate and promote the
      development of adolescent mothers and their children.

PMID- 8551370
TI  - Tympanic versus rectal thermometry in pregnant women.
AB  - OBJECTIVE: To assess the accuracy of the tympanic membrane thermometer for use
      with pregnant women. DESIGN: Cross-sectional descriptive study. SETTING: A major
      medical center in the midwestern United States. PARTICIPANTS: Thirty-three
      hospitalized, afebrile pregnant women. MAIN OUTCOME MEASURES: Tympanic membrane
      thermometers and glass mercury thermometers were used to measure body temperature
      at the ear and rectum, respectively. The results were compared using two
      statistical methods: the Pearson correlation coefficient and a new technique
      suggested by Bland and Altman (1986). RESULTS: Auditory canal temperature
      measured by a tympanic membrane thermometer correlated with rectal temperature as
      measured by a glass mercury thermometer (r = 0.38, p = 0.01). Thus, the tympanic
      membrane thermometer is acceptable for monitoring the body temperature of
      pregnant women. However, the device's estimation of rectal temperature is not
      clinically reliable. CONCLUSIONS: Tympanic membrane thermometers, when applied
      with direct measures, are acceptable for use with pregnant women. It is not
      recommended that the rectal estimate mode be used with pregnant women.

PMID- 8551371
TI  - Pathogenesis of sepsis with central venous catheter use: alternate locus-related
      versus central venous catheter-related sepsis.
AB  - OBJECTIVE: To review literature identifying a central venous catheter (CVC) as
      either a primary or a secondary source of sepsis. DATA SOURCES: Studies of CVC
      use in adults, children, and infants from 1968 to 1994. STUDY SELECTION:
      Selection of 10 studies was based on documented distinction between CVC-related
      and alternate infectious locus-related sepsis. DATA EXTRACTION: Abstracted from
      each study were either total sepsis or colonization rates, as well as the
      percentages of infection related to the CVC and to alternate infectious loci.
      DATA SYNTHESIS: Percentages of alternate-locus-related sepsis can be two to four
      times greater than percentages of CVC-related sepsis. CONCLUSIONS: The potential
      exists for the development of alternate-locus-related sepsis in patients with
      CVCs. Surveillance measures should reflect this potential.

PMID- 8551372
TI  - Common genitourinary infections.
AB  - Vulvovaginal pain, itching, and burning are a triad of symptoms for which women
      frequently seek health care. Often accompanied by vaginal discharge and dysuria,
      these symptoms account for as many as 5 million office visits a year. Proper
      assessment and management of these symptoms by nurses, nurse practitioners, and
      nurse midwives can help to substantially improve a woman's quality of life and
      help prevent long-term problems. Several differing syndromes or infections can be
      the cause of these symptoms. The most common causes are discussed, and a plan for
      management and prevention is presented.

PMID- 8551373
TI  - Sexually transmitted diseases: current and emerging concerns.
AB  - Sexually transmitted diseases (STDs) are epidemic today, with the highest
      prevalence being among adolescents and young adults. If any decrease in incidence
      is to occur, nurses must make a determined effort to identify at-risk individuals
      and groups and empower them through teaching and counseling about strategies of
      primary and secondary prevention. Current and emerging concerns that make
      prevention of STDs difficult include such problems as the huge reservoir of
      infected individuals with no symptoms, the synergy between STDs and human
      immunodeficiency virus infections, and the particular vulnerability of women to
      STDs based on their biology. A holistic approach to care that is sensitive to the
      age, race, culture, and core group characteristics is essential for effective
      prevention efforts.

PMID- 8551374
TI  - Pelvic inflammatory disease: clinical overview.
AB  - Acute pelvic inflammatory disease (PID) adversely affects the health of 1 million
      American women annually. The best understood etiologic organisms are Chlamydia
      trachomatis and Neisseria gonorrhea; however, information regarding the
      contributions of facultative and causative anaerobes continues to emerge. Chronic
      PID presents a diagnostic and management challenge to health care providers.
      Because of morbidity and sequelae the importance of early detection of, and
      intervention for, upper tract pelvic infections cannot be overemphasized. Nursing
      interventions in PID prevention, early assessment, accurate diagnosis, and
      thorough treatment can have a positive impact on women's health.

PMID- 8551375
TI  - Genitourinary infection in older women.
AB  - As they age, women become increasingly susceptible to all infectious processes.
      Compounding increased susceptibility are the aging process and chronic and
      coexisting diseases that can mask or confound an infectious process. Infections
      in older women may present atypically, which hinders diagnosis and treatment. The
      presentation, treatment, and nursing care involved in treating elderly women with
      urinary tract infections and vulvovaginitis are discussed.

PMID- 8551376
TI  - Women at risk for infection: the woman who is chemically dependent.
AB  - Chemical dependency is recognized as an important threat to women's physical and
      emotional well-being. The drug-seeking lifestyle, debilitating effects of drug
      use, and chosen method of administration place women who are chemically dependent
      at increased risk for a variety of infections and other physical and psychologic
      complications. The desire to obtain the drug of choice often overrules the desire
      to maintain self-protective and health-promoting activities. Health care
      professionals are challenged to provide education regarding the potential effects
      of chemical dependency, treatment opportunities, and self-protection strategies
      to assist women in making appropriate health-related decisions. Understanding
      chemical dependency from a women's health perspective promotes the development of
      innovative gender-specific prevention and intervention strategies. This article
      provides an overview of chemical dependency's unique risks and effects on women's
      health and explores strategies for providing relevant information to facilitate
      empowered decision making in this population.

PMID- 8551377
TI  - [Immunohistochemical study on temporal bone of autopsy cases with Mycobacterium
      leprae infection].
AB  - Three temporal bones were obtained en bloc from autopsy cases with lepromatous
      leprosy from the middle cranial fossa side after removing the brain. After
      fixation with 10% formalin followed by sufficient decalcification, the specimens
      were embedded in paraffin en bloc and cut serially to stain every 10th section
      with hematoxylin and eosin (H&E) for anatomical orientation. An
      immunohistochemical study with anti-neurofilament, anti-MBP (myelin basic
      protein), anti-BCG (Bacillus Calmette-Gue'rin) and anti-PGL (Mycobacterium leprae
      specific antiphenolic glycolipid-I) antibodies were performed to vestibular,
      cochlear and facial nerves, respectively, on the basis of anatomical orientation
      of the adjacent H&E sections. In one of three cases, positive staining by anti
      PGL antibodies was recognized only in the facial nerve both in its internal
      auditory meatal and tympanic portions. However, even in this case, no neural
      damage was observed either by anti-neurofilament nor anti-MBP stainings. This
      finding supports the possibility of central neural infection by Mycobacterium
      leprae.

PMID- 8551379
TI  - [Analysis of the breakage process during the measurement of the mechanical
      strength of guinea pig tympanic membranes].
AB  - We analyzed the breakage process of the tympanic membrane in relation to the
      material mechanics, using the microtesting system which we have reported
      previously. 111 fresh tympanic membranes from 56 guinea pigs were used. We
      calculated the stress-strain curve from the load-displacement curve which was
      obtained in this experiment. In addition, we observed the morphological changes
      during the breakage process of the tympanic membrane using optical microscope and
      scanning electron microscope (SEM). We observed multiple notches (small peaks) on
      the stress-strain curve. The first notch was considered to correspond to the
      elastic limit of the tympanic membrane. This first notch appeared at the point
      when the stress was 4.86 MPa and the strain was 0.10. Comparing the stress-strain
      curve to morphological changes, this notch in the stress-strain curve appeared
      when the stress suddenly decreased due to a slit on the tympanic membrane. The
      elastic modulus of the fresh tympanic membrane of guinea pigs was calculated as
      5.71 x 10(-2)mN/microns 2. The maximal stress was 18.5 MPa and this value
      represented the maximal strength of the radial fiber bundles. From these results,
      we can speculate that from a mechanical point of view, the tympanic membrane of
      the guinea pig is a combined material consisting of the radial fiber bundles and
      circular fibers and that at the site of mechanical injury both fibers
      strengthened their interactions with each other.

PMID- 8551378
TI  - [Study on middle ear ventilation using positional tympanometry--post
      mastoidectomy ear].
AB  - The middle ear is a cavity surrounded by solid bone, lined with mucosa with a
      lumen filled with gas. To examine this unique ventilation system under
      atmospheric pressure, the middle ear pressure of 50 normal ears was previously
      examined. Positional tympanometry, whereby the middle ear pressure is increased
      as the subject assumes the lateral position under atmospheric pressure was used.
      As a result, (1) The middle ear pressure was elevated by the change from the
      sitting position to the lateral position. Venous pressure was regarded as
      causative factor of this pressure elevation. (2) The elevation of the middle ear
      pressure in the lateral position suggested gas production from the mastoid cells
      of the middle ear. In this study, a proportion of the mastoid cells were removed
      to resect a tumor of the internal acoustic meatus in conjunction with resection
      of an acoustic tumor. After resection the area was filled with fascia and fatty
      tissue. The middle ear pressure of each subject was monitored to determine the
      effect of a decrease in the mastoid cell volume on middle ear pressure. The
      results were continuously recorded every 12 seconds for the lower ear when the
      subjects were in the lateral position. The following results were obtained. (1)
      The elevation of the middle ear pressure due to positional change among subjects
      which had had acoustic tumors resected was noticeably greater than the elevation
      in normal ears. This is thought to have been the result of an elevation in
      cerebrospinal fluid pressure attributable to positional change, along with an
      elevation in intravenous pressure. (2) We made comparisons of increases in middle
      ear pressure 10 minutes after assuming the lateral position in 14 ears after
      acoustic tumor resection and in 21 normal ears. No noticeable differences were
      found in the middle ear pressure increases between the two groups despite the
      fact that the volume of the mastoid cells in the group that had tumors resected
      had been greatly reduced.

PMID- 8551380
TI  - [Three cases of postoperative laryngopharyngeal edema following nonsimultaneous
      bilateral radical neck dissection].
AB  - Three cases of postoperative laryngopharyngeal edema following nonsimultaneous
      radical neck dissection are presented. Case 1 was a 65-year-old male with tongue
      cancer and left cervical lymph node metastases. Hemiglossectomy, reconstruction
      of the floor of the mouth with a free rectus abdominis flap, and left radical
      neck dissection had been performed. Postoperatively, the tongue and left upper
      neck were irradiated. Seven months later, right cervical lymph node metastases
      were observed. Right radical neck dissection was performed, and immediately after
      extubation, upper airway stenosis due to severe laryngopharyngeal edema occurred.
      Emergent tracheostomy saved his life. Case 2 was a 55-year-old female with tongue
      cancer and right cervical lymph node metastases. Radium needles had been
      implanted in the tongue, and right radical neck dissection was performed. Three
      months later, left cervical lymph node metastases were found. Left radical neck
      dissection was performed and, as in Case 1, upper airway stenosis revealed
      immediately after extubation. Since the situation was anticipated, an immediate
      tracheostomy was done. Case 3 was a 43-year-old male with laryngeal cancer and
      left cervical lymph node metastasis. Irradiation of the larynx and the bilateral
      upper neck followed by left radical neck dissection and partial
      laryngohypopharyngectomy had been performed. Five years later, right cervical
      lymph node metastasis was observed. Right radical neck dissection was performed,
      and laryngoscopic examination before extubation revealed severe laryngopharyngeal
      edema. In this case, tracheostomy was performed before extubation. To our
      knowledge, there have been only five cases of postoperative laryngopharyngeal
      edema, following nonsimultaneous radical neck dissection, reported in the
      literature.

PMID- 8551382
TI  - The p53 tumour suppressor gene and tumour prognosis: is there a relationship?

PMID- 8551381
TI  - [Changes in hearing features according to days from onset of sudden deafness].
AB  - We analyzed 746 patients with idiopathic sudden hearing loss who visited our
      clinic within 16 days after the onset. Patients were divided into 10 groups
      according to the number of days between the initial visit and the onset. Initial
      hearing levels, audiometric types and hearing recoveries were investigated in
      these groups to estimate the natural history of sudden deafness. The results were
      as follows: 1) There were no significant differences among the 10 groups
      regarding the averaged five-frequency hearing levels of initial audiograms. 2)
      Regarding the audiometric types of the initial audiograms, flat and upward slope
      types were frequently seen in the groups who visited us within 6 days. In
      contrast, the population of down slope types gradually increased in the groups
      presenting after 7 days. In the ultimate audiograms, flat and down slope types
      were frequently seen in all groups. 3) There were significant differences among
      the 10 groups regarding the averaged five-frequency improvement (one-way analysis
      of variance, p < 0.01). After 9 days, hearing recovery became less likely.

PMID- 8551383
TI  - Expression of p53 protein has no independent prognostic value in breast cancer.
AB  - A series of 392 female breast carcinomas was analysed immunohistochemically for
      expression of p53 protein with special emphasis on the role of p53 as an
      independent prognostic factor. Altogether, 54.8 per cent of the carcinomas
      expressed p53 protein, with the mean [standard error (SE)] fraction of positive
      nuclei being 17.1 per cent (1.2 per cent). Expression of p53 protein was
      independent of tumour metastasis at diagnosis, axillary lymph node status, tumour
      diameter, histological type, tubule formation, proportion of intraductal growth,
      margin formation, necrosis, DNA ploidy, and S-phase fraction. A high fraction of
      p53-positive nuclei was significantly related to patient age under 70 years, high
      grade, severe nuclear pleomorphism, dense infiltration of tumour by lymphocytes,
      high mitotic index, and high apoptotic index (for all, P < 0.05). Impaired
      survival probability in the entire cohort (P = 0.05) and in the axillary lymph
      node-positive (ANP) tumours (P = 0.015) was associated with a fraction of p53
      positive nuclei less than 25 per cent, while in the axillary lymph node-negative
      (ANN) tumours, expression of p53 had no prognostic value. In multivariate
      analysis, independent prognostic predictors included axillary lymph node status,
      tumour diameter, and mitotic index. In the ANN tumours, tumour diameter, fraction
      of p53-positive nuclei, and tumour grade were independent prognostic factors,
      whereas in the ANP tumours, diameter and mitotic index were the two independent
      prognostic factors. The results suggest that abnormal expression of p53 protein
      is only a weak independent prognostic factor in female breast cancer.

PMID- 8551384
TI  - In situ detection of Epstein-Barr virus in non-small cell lung carcinomas.
AB  - Epstein-Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma and
      lymphoepithelioma-like carcinomas (LELC) of foregut-derived organs. Recently this
      group of EBV-associated carcinomas has been expanded by the identification of the
      virus in conventional adenocarcinomas of the stomach. In situ hybridization (ISH)
      using a sensitive digoxigenin-labelled EBER RNA probe was performed on 167
      consecutive unselected primary non-small cell lung carcinomas, to determine the
      frequency of EBV association in these tumours. Nine cases (5.4 per cent) showed
      strong EBER signals in the tumour cell nuclei. By immunohistochemistry, four of
      the EBER-positive tumours showed patchy expression of the viral latent membrane
      protein (LMP-1) and none showed any expression of the EBV nuclear antigen 2
      (EBNA2). Morphologically, all the positive tumours were LELC, whereas no
      conventional type of non-small cell lung carcinoma showed EBV association. The
      LELC presented a morphological spectrum from undifferentiated to squamoid or
      glandular differentiation. The patients showed a male to female ratio of 8:1. The
      mean age at presentation was 48 years. Smoking was not a risk factor. All
      patients were alive at follow-up periods of 23-52 months. Southern blot analysis
      performed on eight of the nine positive tumours showed a clonal episomal form of
      EBV, suggesting the clonal expansion of an infected tumour cell early in
      oncogenesis. These characteristics of the EBV-associated lung tumours justify
      their consideration as a distinct clinicopathological entity.

PMID- 8551385
TI  - Nuclear and cytoplasmic bcl-2 expression in endometrial hyperplasia and
      adenocarcinoma.
AB  - The bcl-2 proto-oncogene, which inhibits programmed cell death (apoptosis), has
      recently been found to be cyclically expressed in human endometrium. In order to
      investigate its role in endometrial hyperplasia and neoplasia, bcl-2 expression
      was studied in 25 cases of endometrial carcinoma and 20 cases of endometrial
      hyperplasia (eight simple, two complex, and ten atypical hyperplasias). Uniform
      intense cytoplasmic bcl-2 expression was found in all cases of non-atypical
      hyperplasia, and less strong positivity in eight out of ten cases of atypical
      hyperplasia. In well-differentiated carcinomas, nine out of ten showed weak to
      moderate bcl-2 expression, whereas six out of seven poorly differentiated
      carcinomas were bcl-2-negative. Moderately differentiated tumours were an
      intermediate group, with six out of eight being positive. Widespread localization
      of bcl-2 protein to the chromosomes of dividing cells was also demonstrated,
      regardless of cytoplasmic bcl-2 expression, with rare staining of interphase
      nuclei. Our findings suggest a role for bcl-2 in the natural history of
      endometrial neoplasia and studies are needed to determine its usefulness as a
      prognostic marker. The finding of bcl-2 localization to chromosomes has important
      implications for its mode and site of action.

PMID- 8551386
TI  - Expression of bcl-2 oncoprotein in renal cell tumours.
AB  - Expression of bcl-2 is associated with inhibition of apoptosis and extension of
      cell survival. The importance of apoptosis in relation to the development and
      progression of renal cell neoplasia remains undefined so far. In order to
      determine the expression of bcl-2 oncoprotein in normal and neoplastic renal
      cells, 37 renal tumours were investigated by immunolabelling, including 13 clear
      cell carcinomas, ten tubulopapillary carcinomas, four chromophobic renal cell
      carcinomas, and ten oncocytomas. Twenty-six samples of adjacent normal renal
      tissue served as controls. bcl-2 expression was correlated with cell
      proliferation activity as estimated by Ki67 antigen expression, and p53 protein
      expression in the tumour samples. The results demonstrate that in the normal
      kidney, positive bcl-2 immunostaining was present in glomerular parietal
      epithelial cells, in distal tubular cells, and in sparse proximal tubule cells.
      Renal cell tumours showed heterogeneous bcl-2 expression according to the tumour
      cell type. While the majority of carcinomas of clear cell type were usually
      negative or contained sparsely distributed positive cells, all tubulopapillary
      carcinomas were consistently positive for bcl-2. In oncocytomas and chromophobic
      carcinomas, there was a low percentage of bcl-2 immunoreactive tumour cells; some
      nuclear bcl-2 positivity was detected in one chromophobic tumour. These findings
      indicate variable bcl-2 oncoprotein expression in different types of renal cell
      tumours, with the highest level of expression in tubulopapillary carcinomas. No
      clear relationship was found between nuclear grade, cell proliferation activity,
      and level of bcl-2 expression. p53 protein was detected in only one
      tubulopapillary carcinoma.

PMID- 8551387
TI  - Differential expression of the c-kit proto-oncogene in germ cell tumours.
AB  - The c-kit proto-oncogene product and its ligand stem cell factor play an
      important role in haematopoiesis, spermatogenesis, and melanogenesis. Using an
      anti-c-kit antiserum raised against a synthetic peptide, we studied the
      immunohistochemical expression of the c-kit gene product in 60 germ cell tumours
      (GCTs) (53 testicular, 7 extragonadal), derived from primary GCTs in 45 cases and
      metastatic tumours in 15 cases. Twenty-eight out of 28 seminomas showed c-kit
      membranous staining in the majority of cells. A similar pattern of expression was
      seen in intratubular germ cell neoplasia. Nine out of 29 (32 per cent) non
      seminomas displayed cytoplasmic, but not membranous, c-kit immunoreactivity in
      occasional cells. In three mixed GCTs, c-kit expression was limited to the
      seminoma component. In normal testis, c-kit expression was observed in some basal
      tubular cells, corresponding to undifferentiated spermatogonia. These results
      suggest a role for c-kit in the oncogenesis of GCT, where down-regulation of c
      kit might be a critical step during progression from seminomas to non-seminomas.
      Immunohistochemical analysis of c-kit should be considered as a diagnostic aid
      for GCT and in particular may be helpful in the identification of certain
      extragonadal seminomas.

PMID- 8551388
TI  - Expression of vascular endothelial growth factor in renal vascular disease and
      renal allografts.
AB  - Vascular endothelial growth factor (VEGF) is a dimeric glycoprotein that exerts a
      proliferative effect specifically on endothelial cells. VEGF can increase
      vascular permeability and collagenase activity, is chemotactic for monocytes, and
      may dilate blood vessels. It can be induced by phorbol ester and cAMP in both
      mesenchymal and epithelial cells. In vitro cell culture experiments suggest that
      VEGF is upregulated by oxygen deprivation. In this study we tested whether in
      vivo acute and/or chronic reduction of renal blood flow by vascular obstruction
      would result in increased expression of VEGF mRNA and protein. Three normal
      kidneys, five human kidneys with narrowing of preglomerular vessels by vascular
      rejection or by vasculitis, and eight kidneys with nephrosclerosis and/or
      diabetic nephropathy were examined. In situ hybridization with 35S-labelled
      riboprobes showed a pronounced expression of VEGF mRNA in acutely hypoxic
      proximal and distal tubules of both the cortex and medulla; VEGF protein was
      demonstrated in the epithelia of these tubules by immunohistochemistry. In
      kidneys with chronically reduced blood flow, the majority of atrophic tubules
      were negative for VEGF mRNA and protein, although interstitial cells expressed
      VEGF mRNA. In arcuate arteries showing intimal and adventitial fibrosis, some
      medial smooth muscle cells were positive for VEGF mRNA. In glomeruli with
      segmental sclerosis, viable podocytes showed a prominent signal for VEGF mRNA.
      Mesangial cells did not express VEGF in the cases studied. It is possible that
      hypoxia itself led to the upregulation of VEGF in tubular epithelia and vascular
      smooth muscle cells. The vasodilatory and permeability-promoting effects of the
      endothelial growth factor produced by damaged tubular epithelia may constitute a
      mechanism to alleviate a decrease in blood flow and substrate availability and to
      re-establish vascular integrity.

PMID- 8551389
TI  - Role of endothelial cells in the development of glomerular lesions of
      mesangiocapillary glomerulonephritis.
AB  - The histological and ultrastructural changes of mesangiocapillary
      glomerulonephritis (MCGN) are not unique to this entity: splitting of basement
      membrane (BM) is seen in a number of conditions with an altered coagulation
      pattern. The distribution of endothelial cells in the glomerular capillaries in
      five cases of MCGN was studied by light and electron microscopy and
      immunocytochemistry; endothelial cells were stained with peroxidase or FITC
      conjugated antibodies against Factor VIII-related antigen or CD34 antigen and
      observed with conventional light/immunofluorescence microscopy and confocal laser
      scanning microscopy for three-dimensional reconstruction. Electron microscopy was
      performed with colloidal gold labelling. Endothelial cells were shown to be
      present within the duplicated basement membranes of capillaries and continuity
      was demonstrated with endothelial cells lining the capillary lumina. These
      results suggest that endothelial cells as well as mesangial cells can participate
      in the formation of the characteristic double contour of capillary walls in MCGN,
      especially in the early stages. There are some similarities to the changes seen
      in larger arteries as a consequence of thrombotic disease.

PMID- 8551390
TI  - Quantitation and prognostic value of breast cancer angiogenesis: comparison of
      microvessel density, Chalkley count, and computer image analysis.
AB  - In some studies of breast cancer, quantitation of immunohistochemically
      highlighted microvessel 'hot spots' has been shown to be a powerful prognostic
      tool. However, the antibody used, the number and size of the 'hot spots'
      assessed, and the stratification of patients into high and low vascular groups
      vary between studies. Furthermore, little is known about the relationship between
      microvessel density and other vascular parameters. These uncertainties and the
      laborious nature of the technique make it unsuitable for diagnostic practice.
      Both manual and computerized image analysis techniques were used in this study to
      examine the relationship between microvessel density and the vascular parameters
      in different sized microscopic fields in a pilot series of 30 invasive breast
      carcinomas. Automated pixel analysis of immunohistochemical staining, Chalkley
      point counting, and observer subjective vascular grading were also assessed as
      more rapid methods of measuring tumour vascularity. A Chalkley count was also
      performed on a further 211 invasive breast carcinomas. Significant correlations
      were observed between manual microvessel density and luminal perimeter (r = 0.6,
      P = 0.0004), luminal area (r = 0.56, P = 0.002), and microvessel number (r =
      0.57, P = 0.0009) by computerized analysis. There were also significant
      correlations between the microscopic hot spots of 0.155 mm2 and 0.848 mm2 for
      microvessel number (r = 0.81, P < 0.00005), luminal perimeter (r = 0.78, P <
      0.00005), and luminal area (r = 0.65, P = 0.0001). In addition, a significant
      correlation was observed between microvessel density and both subjective vascular
      grade (P = 0.002) and Chalkley count (P = 0.0001). A significant reduction in
      overall survival was observed between patients stratified by Chalkley count in
      both a univariate (P = 0.02) and a multivariate (P = 0.05) analysis in the 211
      invasive breast carcinomas. These findings show that Chalkley counting is a rapid
      method of quantifying tumour angiogenesis and gives independent prognostic
      information which might be useful in diagnostic practice.

PMID- 8551391
TI  - A cautionary note regarding the application of Ki-67 antibodies to paraffin
      embedded breast cancers.
AB  - Immunocytochemical studies examining the Ki-67 proliferation marker in paraffin
      embedded material have recently been made possible by the availability of several
      antibodies, notably MIB-1, which are readily applicable to microwaved sections.
      Using breast cancer material, the present study examines correlations shown by
      these new paraffin assays and also by PCNA (proliferating cell nuclear antigen),
      an existing marker of proliferation, with the established Ki-67 cryosection
      assay. Paraffin sections were microwaved prior to incubation with Ki-67 or MIB-1
      antibodies. Signal detection was carried out with a biotinylated secondary
      antibody, peroxidase-conjugated streptavidin, and DAB/H2O2 chromogen. The results
      suggest that caution is required when studying proliferation in paraffin-embedded
      breast cancers by immunostaining using Ki-67 antibodies. Nuclear staining in wax
      sections (Ki-Par, MIB-1, PCNA) greatly exceeded that in cryosections (Ki-Froz)
      and thus correlations were notably absent between Ki-Par or PCNA immunostaining
      and the routine Ki-Froz assay. Immunostaining with MIB-1 or PCNA may, however, be
      useful to assess proliferation if cut-offs are applied to eliminate weak
      immunostaining associated with wax sections. Thus, an approximately linear
      relationship was seen between MIB-1/Ki-Froz, which was improved if only
      moderately or moderately/strongly MIB-1-positive cells were scored. Similarly, a
      significant correlation was also revealed between PCNA/Ki-Froz if such a cut-off
      was applied.

PMID- 8551392
TI  - Vascular networks within the stroma of human long-term bone marrow cultures.
AB  - The formation of branching and anastomosing vascular structures has been
      demonstrated within the stromal layers of human long-term bone marrow cultures
      (LTBMCs). Such organized vascular structures have not been described previously
      and may be of functional importance, as adherent granulocyte-predominant
      haemopoietic foci were more numerous in their interstices and margins than
      elsewhere in the stromal layers. Mature granulocytes were seen within vascular
      lumina in a few instances, possibly indicating an attempt to recapitulate the
      normal process of egress of neutrophils from bone marrow into the circulation.
      Immunostaining showed that the vascular structures expressed CD31, CD34, and
      CD105 (endoglin), which were not expressed by stromal fibroblastic cells.
      Collagen IV and laminin, expressed throughout the stroma, were present in
      increased amounts where vascular arrays were seen. In contrast, von Willebrand
      factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1) were expressed
      equally by the vascular arrays and by stromal fibroblastic cells. Neither the
      arrays nor the general stroma expressed intercellular adhesion molecule-1 (ICAM
      1), ICAM-2, ICAM-3, or endothelial leukocyte adhesion molecule-1 (ELAM-1).

PMID- 8551393
TI  - Cytogenetic and pathogenic effects of long and short amosite asbestos.
AB  - This study utilized two samples of amosite asbestos which differ in their length,
      but not in their diameter and which have been shown previously to have very
      different abilities to cause pathology in rats exposed by instillation or
      inhalation. The activity of these amosite samples in causing chromosomal
      aberrations in Chinese hamster ovary cells in culture was examined, along with
      the effect of the glutathione (GSH) synthesis-inhibiting agent buthionine
      sulphoximine. The incidence of chromosomal aberrations in cells treated with the
      short fibre sample was similar to control levels; the long amosite sample caused
      significantly more chromosomal aberrations than the short fibre sample. When
      cells were treated with buthionine sulphoximine to decrease the levels of
      intracellular glutathione, the incidence of chromosomal aberrations was increased
      in the control cells, but also on treatment with both short and long amosite, the
      long sample again being considerably more active than the short. The
      pathogenicity of the long amosite may result from the ability of the fibres to
      cause chromosome damage, while the enhancement of this damage caused by
      decreasing intracellular glutathione suggests that the asbestos fibres may impose
      an oxidant stress on the cells which contributes to these aberrations.

PMID- 8551394
TI  - Thymic epithelial neoplasms in transgenic mice expressing SV40 T antigen under
      the control of an erythroid-specific enhancer.
AB  - The beta-globin locus control region is known to be a powerful erythroid-specific
      enhancer. In an attempt to produce immortalized erythroid percursor cells,
      transgenic mice have been generated with the simian virus (SV) 40 T antigen gene
      under the control of the locus control region. As previously reported, transgenic
      mice did not develop erythroleukaemia, but rather succumbed to insulinomas and
      poorly differentiated rhabdomyosarcomas. This paper describes additional mice
      containing this transgene that developed thymomas of the mixed
      epithelial/lymphocytic type, in which only the epithelial component expressed the
      T antigen. Epithelial cell lines have been established from these tumours. This
      system may be useful in future studies on the pathogenesis of thymomas and the
      function of thymic epithelial cells.

PMID- 8551395
TI  - Inhibition of gastric cell proliferation by acetaldehyde.
AB  - Helicobacter pylori possesses alcohol dehydrogenase activity and is capable of
      producing acetaldehyde from ethanol in vitro. Acetaldehyde is a toxic and
      reactive compound and has been shown to inhibit the proliferation of many
      different cell lines in vitro. To study the effects of acetaldehyde on the
      proliferation of gastric epithelial cells in vivo, we employed an
      immunohistochemical method after labelling proliferating cells with 5'-bromo-2'
      deoxyuridine in rats receiving acetaldehyde intragastrically. Chronic (16 weeks)
      exposure of gastric mucosa to acetaldehyde given to rats in their drinking water
      in concentrations of 10 or 20 mM resulted in significant (P < 0.05) inhibition of
      gastric epithelial cell proliferation, expressed as 332 +/- 36, 348 +/- 8, and
      695 +/- 15 proliferating cells per ten high-power (x 400) fields in the groups
      drinking 10 mM acetaldehyde, 20 mM acetaldehyde, and in controls respectively. In
      an acute study, significant inhibition of proliferation was observed after as few
      as 4 days of exposure to acetaldehyde, but only when a higher dose (50 mM) of
      acetaldehyde was given (438 +/- 44 versus 615 +/- 19 in controls, P < 0.05). The
      inhibition of gastric cell renewal by acetaldehyde may play a role in the
      pathogenesis of ethanol- and/or H. pylori-associated gastric diseases by
      inhibiting normal gastric mucosal protection and repair.

PMID- 8551396
TI  - Protein extraction and western blotting from methacarn-fixed tissue.
AB  - Polyacrylamide gel electrophoresis (PAGE) of proteins with subsequent western
      blotting has become a routine technique for the analysis of proteins from both
      cultured cells and fresh whole tissue. We have developed a method to extract
      proteins from methacarn-fixed tissue which renders them suitable for SDS-PAGE and
      western blotting. With a panel of antibodies to specific intermediate filaments,
      transforming growth factor-alpha (TGF-alpha), and albumin, immunohistochemistry
      was performed in parallel with western blotting on sections cut from methacarn
      fixed samples of normal rat liver and liver from rats treated under a regime
      which induces oval cell proliferation. Immunohistochemistry enabled the
      determination of changes in tissue distribution and abundance of the target
      proteins, which was mirrored by the corresponding western blot data. This
      technique can be especially effective when used in conjunction with
      immunohistochemistry. Tissue samples are easy to prepare, avoiding the
      precautions which need to be taken when handling fresh tissue (Abstract: J Pathol
      1994; 173S: No. 41).

PMID- 8551397
TI  - Pediatric echocardiography: current role and a review of technical advances.
AB  - Advances in echocardiography have enhanced our diagnostic imaging capabilities
      for congenital heart defects. In addition to improved resolution of two
      dimensional images, cardiac hemodynamic assessment is possible with the use of
      Doppler, color Doppler, and stress echocardiography. Transesophageal
      echocardiography has allowed intraoperative assessment of cardiac repairs, and
      fetal echocardiography has allowed development of the field of fetal cardiology.
      The developing areas of intravascular ultrasonography and three-dimensional
      echocardiography show promise for the future. Echocardiography continues to
      revolutionize our ability to diagnose congenital heart defects accurately.

PMID- 8551398
TI  - Invasive Haemophilus influenzae type b infection in a child with familial
      deficiency of the beta subunit of the eighth component of complement.
AB  - A child who had had meningitis caused by Haemophilus influenzae type b, and then
      had meningococcal meningitis, was found to have familial deficiency of the beta
      subunit of the eighth component of complement. The child had not received the H.
      influenzae type b vaccine. If this deficiency is discovered, we recommend that
      family members be screened, regardless of their health status.

PMID- 8551399
TI  - Genotype-dependent variability in flow cytometric evaluation of reduced
      nicotinamide adenine dinucleotide phosphate oxidase function in patients with
      chronic granulomatous disease.
AB  - We studied phagocyte reduced nicotinamide adenine dinucleotide phosphate function
      to evaluate production of reactive oxygen species in both X-linked and autosomal
      forms of chronic granulomatous disease. We found a consistent and significant
      difference between the activated granulocyte response of the X-linked (gp91
      phagocyte oxidase) form of chronic granulomatous disease (n = 18) and that of the
      most common autosomal recessive (p47-phagocyte oxidase) form of the disease (n =
      17). The data indicate that mutations in the p47-phagocyte oxidase component of
      the reduced nicotinamide adenine dinucleotide phosphate oxidase component do not
      completely prevent oxidation despite severe defects in superoxide generation.

PMID- 8551400
TI  - Predictors of early childhood outcome in candidates for extracorporeal membrane
      oxygenation.
AB  - OBJECTIVE: To examine the effect of neonatal risk factors and treatment strategy
      on pulmonary, growth, and neurodevelopmental outcome of candidates for
      extracorporeal membrane oxygenation (ECMO). DESIGN: We prospectively assessed
      growth and neurodevelopmental outcome in a cohort of 190 neonates who had severe
      respiratory failure, no major congenital anomalies, and met institutional
      criteria for the use of ECMO. The relationships among perinatal risk factors,
      neonatal outcome, postnatal growth, and neurodevelopmental outcome were studied
      by univariate and multivariate analyses. RESULTS: Compared with 52 infants
      successfully treated with conventional or high-frequency ventilation, the 138
      ECMO survivors were more mature, had earlier, more severe pulmonary disease, and
      were more likely to have meconium aspiration. The ECMO survivors had
      significantly fewer ventilator days (9 vs 11), hospital days (23 vs 29), and less
      (12% vs 25%) chronic lung disease (CLD). At 12 to 30 months, mean developmental
      scores of ECMO survivors were similar to those of infants who survived without
      ECMO. Infants with CLD had significantly lower motor scores (86 +/- 23 vs 100 +/-
      19) and were more likely to have cerebral palsy (27% vs 6%) than those without
      CLD. The risk of adverse neurodevelopmental outcome was independently increased
      by CLD (odds ratio, 2.4; confidence interval, 1.2 to 4.6) and moderate or severe
      neonatal neuroimaging abnormalities (odds ratio, 6.4; confidence interval, 1.9 to
      21.9). CONCLUSIONS: Neonatal ECMO candidates treated with ECMO did as well or
      better than neonates whose conditions were managed with alternate treatment
      strategies. Adverse neurodevelopmental outcome was predicted by moderate or
      severe neonatal neuroimaging abnormalities and CLD, not by treatment with ECMO.

PMID- 8551401
TI  - Production of pulmonary vasodilation by tolazoline, independent of nitric oxide
      production in neonatal lambs.
AB  - OBJECTIVE: To determine whether tolazoline reduces pulmonary vascular resistance
      (PVR) by means of endogenous nitric oxide production. DESIGN: Thirty newborn
      lambs (2 to 7 days of age) were anesthetized with pentobarbital, and their lungs
      were ventilated through an endotracheal tube. Intravascular catheters were placed
      in the left ventricle, descending aorta, right atrium, and pulmonary artery for
      continuous monitoring of intravascular pressures. Cardiac output was measured
      with radiolabeled microspheres. Arterial carbon dioxide pressure and pH were
      maintained in a normal range throughout the experiments. Animals were randomly
      assigned to the following groups: group 1, lungs ventilated with a hypoxic gas
      mixture and administered tolazoline; group 2, given N omega-nitro-L-arginine (L
      NA) (5 mg/min intravenously for 60 minutes) and tolazoline; group 3, given L-NA
      with hypoxia and tolazoline. Acetylcholine (0.5 microgram/kg) was injected into
      the right atrium to assess pulmonary nitric oxide synthase activity before and
      after the L-NA infusion. Data were analyzed by analysis of variance. RESULTS: L
      NA inhibited the acetylcholine-induced reduction in mean pulmonary artery
      pressure (MPAP) by more than 75%. Hypoxia and L-NA increased both MPAP and PVR.
      Tolazoline produced immediate reductions in both MPAP and PVR in all three groups
      (group 1, 27% +/- 3% and 50% +/- 5%; group 2, 34% +/- 5% and 50% +/- 6%; and
      group 3, 31% +/- 4% and 46% +/- 5%, respectively). CONCLUSIONS: These results
      suggest that tolazoline produces vasodilation independent of nitric oxide
      production. Understanding the mechanism by which tolazoline produces pulmonary
      vasodilation may provide insight into the clinical use of this drug and
      information regarding other potential endogenous mediators of pulmonary vasomotor
      tone in the neonate.

PMID- 8551402
TI  - Lumbar puncture in the evaluation of possible asymptomatic congenital syphilis in
      neonates.
AB  - OBJECTIVE: To evaluate the usefulness of lumbar puncture (LP) in the initial
      evaluation of symptom-free infants for congenital syphilis. STUDY DESIGN: We
      retrospectively studied infants who had successful LPs and were born to untreated
      or inadequately treated seropositive women between 1990 and 1993 in two hospitals
      in Washington, D.C. We identified 329 such symptom-free infants (syphilis group).
      The cerebrospinal fluid (CSF) VDRL was reactive in two (0.6%) infants. The CSF
      leukocyte and protein concentrations of these infants were compared with those in
      84 symptom-free control infants who were born to seronegative women and who had
      LPs performed in 1993 to rule out sepsis because of associated risk factors.
      Control infants had negative results for bacterial cultures (CSF and blood) and
      bacterial antigen tests (CSF and urine). RESULTS: Thirty control subjects and 67
      infants in the syphilis group had traumatic taps (CSF erythrocytes > 500 x
      10(6)/L), and hence were excluded from the analysis of cell count and proteins.
      Birth weights and gestational ages were similar in both groups. The CSF leukocyte
      and protein values were similar in the syphilis group and in control infants:
      mean CSF leukocytes 7.7 x 10(6)/L (mean 7.7/mm3, range 0 to 57/mm3, SD 8.8)
      versus 6.9 x 10(6)/L (mean 6.9/mm3, range 0 to 31/mm3, SD 7), p = 0.5, and mean
      protein concentration 981 mg/L (range 270 to 2280 mg/L, SD 376) versus 936 mg/L
      (range 360 to 1750 mg/L, SD 368), p = 0.96, respectively. The combination of CSF
      leukocyte values > 5 x 10(6)/L (> 5/mm3) or protein values > 400 mg/L (> 40
      mg/dl) was found in 97.8% of the infants in the syphilis group, compared with
      95.3% of the control group. CONCLUSION: Because of the low yield of reactive CSF
      VDRL and the similar CSF leukocyte and protein values in the syphilis group and
      the control infants, the role of routine LP in the initial evaluation of symptom
      free infants for congenital syphilis should be reconsidered.

PMID- 8551403
TI  - Effect of parenteral amino acids on leucine and urea kinetics in preterm infants.
AB  - OBJECTIVE: To examine the effect of two commonly used parenteral alimentation
      amino acid mixtures on whole-body leucine and urea kinetics. METHODS: Ten stable
      preterm infants were studied during the first 4 weeks after birth. Six infants
      received a mixture containing higher branched-chain amino acids, lower glycine
      plus added dicarboxylic acids formulation (Trophamine), and four received a
      standard amino acid mixture (Aminosyn). Whole-body protein turnover was measured
      with (1-13C)leucine tracer, and the rate of oxidation of protein was calculated
      by quantifying the appearance of carbon 13 from leucine in carbon dioxide as well
      as from rates of urea synthesis estimated by using (15N2)urea tracer. Energy
      consumption and substrate oxidation were quantified by indirect respiratory
      calorimetry. Infants were given similar quantities of energy (approximately 61
      kcal/kg per day), glucose (approximately 10.7 mg/kg per minute) and protein
      (approximately 2.1 gm/kg per day). RESULTS: There was no significant difference
      in the rate of appearance of leucine in the two groups. However, the fraction of
      leucine oxidized (p = 0.002) and total rte of oxidation of leucine was higher in
      the Trophamine group. Thus additional branched-chain amino acids resulted in an
      increased contribution of C-1 of leucine to expired CO2. The rate of urea N
      synthesis was also similar in the two groups (Trophamine: 2.92 +/- 0.87 mg N/kg
      per hour; Aminosyn: 2.70 +/- 1.18 mg N/kg per hour). CONCLUSIONS: Although the
      use of Trophamine normalizes the blood amino acid pattern, it does not appear to
      improve nitrogen/protein kinetics. Furthermore, the additional branched-chain
      amino acids are disposed of by increased oxidation.

PMID- 8551404
TI  - A two-year follow-up of neonates with presumed sepsis treated with recombinant
      human granulocyte colony-stimulating factor during the first week of life.
AB  - We have previously reported that recombinant human granulocyte colony-stimulating
      factor was well tolerated and resulted in sustained neutrophilia and improvement
      of neutrophil functions in newborn infants with presumed sepsis. We now report a
      2-year follow-up on 21 of the initial cohort of 28 patients. Treatment with
      recombinant human granulocyte colony-stimulating factor in neonates with presumed
      sepsis was not associated with any long-term adverse hematologic, immunologic, or
      developmental effects.

PMID- 8551405
TI  - Neonatal thrombocytopenia caused by passive transfer of anti-PLA1 antibody by
      blood transfusion.
AB  - A premature male infant with hyaline membrane disease received a 34 ml
      transfusion of packed erythrocytes from a CPDA1 blood unit on day 2 with no
      adverse consequences. On day 34 he was given a transfusion, and the platelet
      count decreased. Intravenous immune globulin therapy was initiated and the
      platelet count steadily increased. Human leukocyte (HLA) antigen and platelet
      antibody testing showed that the thrombocytopenia was due to passive transfer of
      platelet-specific antibody from the blood donor.

PMID- 8551406
TI  - Treatment of hemangiomas of infants with high doses of prednisone.
AB  - OBJECTIVE: We reviewed our experience with the use of oral corticosteroid therapy
      in treating hemangiomas of infants to determine the optimal effective dose. STUDY
      DESIGN: During a 24-year period, 60 infants with hemangiomas were treated with an
      initial dose of either 3 or 5 mg/kg per day of orally administered prednisone for
      a period ranging from 6 to 12 weeks. Involution of the hemangioma and re-growth.
      were monitored. RESULTS: Overall, excellent and rapid results were achieved in
      68% of infants and good results occurred in 25%. In 7% treatment was deemed to
      have failed. Forty-seven of 60 patients received one course of therapy, 8
      received 2 courses, and 5 required 3 courses. An initial dose of 5 mg/kg per day
      oral prednisone therapy was more effective than 3 mg/kg per day. Side effects
      were not serious and resolved after discontinuation of therapy. CONCLUSIONS: High
      oral doses of corticosteroids (5 mg/kg per day prednisone) provide an effective,
      rapid, and safe modality of treatment of hemangiomas of infants. We recommend
      that treatment continue for 6 to 8 weeks, and in more severe cases for as long as
      12 weeks.

PMID- 8551407
TI  - Treatment of immune globulin-resistant Kawasaki disease with pulsed doses of
      corticosteroids.
AB  - We describe four children with Kawasaki disease resistant to treatment with
      intravenously administered immune globulin who were treated with high doses of
      methylprednisolone. All four patients apparently responded with normalization of
      symptoms, and none had significant progression of coronary artery abnormalities
      or adverse events. We recommend pulse methylprednisolone therapy (30 mg/kg per
      day) during a 1- to 3-day period for patients with Kawasaki disease who do not
      respond to intravenous immune globulin therapy or who have recrudescent disease
      after adequate therapy.

PMID- 8551408
TI  - Liver biopsy findings in patients with juvenile rheumatoid arthritis receiving
      long-term, weekly methotrexate therapy.
AB  - We performed percutaneous liver biopsy in nine children who had received a weekly
      dose of methotrexate, 10 mg/m2 per week, for at least 3 years to address the
      concern about subclinical liver toxicity from single, weekly, low-dose
      methotrexate therapy for juvenile rheumatoid arthritis. No patient had clinical
      or biochemical evidence of liver injury. All biopsy results were interpreted as
      normal. These results suggest that the recommendations of the American College of
      Rheumatology for adults receiving single weekly methotrexate therapy for
      rheumatoid arthritis can be extended to children.

PMID- 8551409
TI  - Routine diagnostic imaging for childhood urinary tract infections: a systematic
      overview.
AB  - OBJECTIVE: To assess the quality of the evidence on which current recommendations
      for routine diagnostic imaging for childhood urinary tract infection are based.
      METHODS: A systematic overview of the literature using the MEDLINE database (1966
      to October 1994), article bibliographies, and a manual search of current
      publications using Current Contents, was undertaken. Preset criteria were used to
      categorize study sample and design, and interrater reliability was assessed with
      a random sample. RESULTS: A total of 434 publications were evaluated, and 63
      studies met the criteria for inclusion. There was 100% interrater agreement on
      inclusion eligibility and design classification. No controlled trials or analytic
      studies evaluating routine diagnostic imaging were found. All 63 studies were
      descriptive, and only 10 were prospective. None of the studies provided evidence
      of the impact of routine imaging on the development of renal scars and clinical
      outcomes in children with their first urinary tract infection. CONCLUSION:
      Methodologically sound, prospective studies are needed to assess whether children
      with their first urinary tract infection who have routine diagnostic imaging are
      better off than children who have imaging for specific indications. We conclude
      that the current recommendations are not based on firm evidence.

PMID- 8551410
TI  - Production of interleukin-5 and the suppressive effect of cyclosporin A in
      childhood severe atopic dermatitis.
AB  - A child with severe atopic dermatitis had marked improvement with oral
      cyclosporin A (CyA) therapy. The function of activated T lymphocytes and serum
      interleukin-5 concentrations were reduced. The expression and production of
      interleukin-5 were high, but were suppressed during CyA therapy and by CyA in
      vitro. Oral CyA therapy may be useful for severe atopic dermatitis.

PMID- 8551411
TI  - Sidney Farber (1903-1973).

PMID- 8551412
TI  - Hemolysis after treatment with ceftriaxone.

PMID- 8551413
TI  - Furosemide-associated fever.

PMID- 8551414
TI  - Nutrition via gastrostomy tube in children with cancer.

PMID- 8551415
TI  - Efficacy of the Flutter device for airway mucus clearance in patients with cystic
      fibrosis.

PMID- 8551416
TI  - Precocious puberty, growth hormone deficiency, and neurofibromatosis.

PMID- 8551417
TI  - Effect of circumcision on incidence of urinary tract infection in preschool boys.
AB  - OBJECTIVE: To determine whether circumcision decreases the risk of symptomatic
      urinary tract infection (UTI) in boys less than 5 years of age. STUDY DESIGN: A
      case-control study (1993 to 1995) in the setting of a large ambulatory pediatric
      service. Case subjects and control subjects were drawn from the same population.
      One hundred forty-four boys less than 5 years of age (median age, 5.8 months) who
      had a microbiologically proven symptomatic UTI (case subjects), were compared
      with 742 boys (median age, 21.0 months) who did not have a UTI (control
      subjects). The proportion of case and control subjects who were circumcised in
      each group was compared with the use of the chi-square test, with the strength of
      association between circumcision and UTI expressed in terms of an odds ratio. To
      determine whether age was a confounder or an effect-modifier, we stratified the
      groups by age (< 1 year; > or = 1 year) and analyzed by the method of Mantel
      Haenszel. RESULTS: Of the 144 preschool boys with UTI, 2 (1.4%) were circumcised,
      compared with 47 (6.3%) of the 742 control subjects (chi-square value = 5.6; p =
      0.02; odds ratio, 0.21; 95% confidence intervals, 0.06 to 0.76). There was no
      evidence that age was a confounder or modified the protective effect of
      circumcision on the development of UTI (Mantel-Haenszel chi-square value = 6.0; p
      = 0.01; combined odds ratio, 0.18; 95% confidence intervals, 0.05 to 0.71;
      Breslow-Day test of homogeneity chi-square value = 0.6; p = 0.4). CONCLUSIONS:
      Circumcision decreases the risk of symptomatic UTI in preschool boys. The
      protective effect is independent of age.

PMID- 8551418
TI  - Bone density in children and adolescents with cystic fibrosis.
AB  - OBJECTIVE: To assess bone mineralization in children and adolescents with cystic
      fibrosis. DESIGN: A cross-sectional, observational study of bone mineral density
      (BMD) in the lumbar vertebrae and the proximal femur of 62 patients aged 4.9 to
      17.8 years (mean, 10.7 years). The age-normalized BMD findings (z scores) were
      correlated with multiple variables, including measures of pulmonary disease,
      nutritional status and growth, genotype, calcium intake, and serum 25
      hydroxyvitamin D and 1,25-dihydroxyvitamin D levels. RESULTS: The mean BMD z
      score was -1.03 +/- 0.14 (+/- SE) in the lumbar vertebrae and -0.71 +/- 0.17 in
      the proximal femur. The BMD in this age range declined relative to normal values
      at a rapid rate of roughly 1 SD every 6 to 8 years. The BMD z scores correlated
      well with multiple measures of disease severity, particularly weight and forced
      expiratory volume in 1 second. CONCLUSIONS: Significant osteoporosis in adults
      with CF results at least in part from a failure to accumulate bone mineral at a
      normal rate during skeletal growth and development. The cause of this is likely
      multifactorial. With increasing longevity, the skeletal consequences of CF become
      an important consideration.

PMID- 8551419
TI  - Variability in duration of stay in pediatric intensive care units: a
      multiinstitutional study.
AB  - OBJECTIVE: Development of a statistical model to predict length of stay (LOS) in
      a pediatric intensive care unit (PICU) that adjusts for patient-related risk
      factors at admission. DESIGN: Randomized selection of sites by cluster sampling
      from a 1989 national survey of all hospitals with PICUs, stratified for four
      quality-of-care factors into 16 clusters (size, presence of an intensive care
      specialist, medical school affiliation, coordination of care). The data
      collection was prospective in the selected units. PATIENTS: 5415 consecutive
      medical, surgical, or emergency admissions to 16 PICUs. MEASUREMENTS: Patients:
      Pediatric Risk of Mortality (PRISM) score for the initial 24 hours, admission
      diagnosis classified into system and cause of the primary dysfunction, operative
      status, preadmission care, critical care modalities required during the first 24
      hours, age, sex, PICU length of stay, and outcome. PICU sites: admission volume,
      coordination of care, presence of an intensivist, presence of residents, and
      number of pediatric ICU and pediatric hospital beds. METHODS: Log-logistic
      regression analysis of LOS on patient-related and institution-related factors.
      RESULTS: Significant (p < 0.05) patient-related predictors of LOS included PRISM,
      10 diagnostic groups, 3 preadmission factors (operative status,
      inpatient/outpatient, previous PICU admission), and first-day use of mechanical
      ventilation. The ratio of observed to predicted LOS varied among PICUs from 0.83
      to 1.25, with three PICUs displaying significantly (p < 0.05) shorter and three
      PICUs longer LOS. The PICU factors associated (p < 0.05) with shorter (5% to 11%)
      LOS were presence of an intensivist, presence of residents, and coordination of
      care, whereas an increased ratio of PICU to hospital beds was associated with
      longer (p < 0.05) LOS. Medical school affiliation, admission volume, number of
      pediatric hospital beds, and PICU mortality rates did not have statistically
      significant effects on LOS when adjusted for patient conditions. CONCLUSIONS: The
      predictor can be used to adjust LOS in PICUs for patient-related risk factors,
      enabling the comparison of resource utilization among different institutions.
      Organizational factors known to foster team-oriented care are associated with
      shorter LOS, whereas increased relative PICU size may pose an incentive to keep
      PICU beds occupied longer.

PMID- 8551420
TI  - A double-blind clinical trial comparing World Health Organization oral
      rehydration solution with a reduced osmolarity solution containing equal amounts
      of sodium and glucose.
AB  - OBJECTIVE: To compare the safety and efficacy of an oral rehydration solution
      (ORS) containing 75 mmol/L of sodium and glucose each with the standard World
      Health Organization (WHO) ORS among Egyptian children with acute diarrhea.
      METHODS: One hundred ninety boys, aged 1 to 24 months, who were admitted to the
      hospital with acute diarrhea and signs of dehydration were randomly assigned to
      receive either standard ORS (311 mmol/L) or a reduced osmolarity ORS (245
      mmol/L). Intake and output were measured every 3 hours. RESULTS: In the group
      treated with reduced osmolarity ORS, the mean stool output during the rehydration
      phase was 36% lower (95% confidence interval, 1%, 100%) than in those treated
      with WHO ORS. The relative risk of vomiting during the rehydration phase was
      significantly lower in children treated with reduced osmolarity ORS (relative
      risk, 2.4; 95% confidence interval, 1.2, 4.8). During the maintenance phase,
      stool output, mean intake of food and ORS, duration of diarrhea, and weight gain
      were similar in the treatment groups. The relative risk of treatment failure
      (need for unscheduled administration of intravenous fluids) was significantly
      increased in children receiving standard WHO ORS (relative risk, 7.9; 95%
      confidence interval, 1.1, 60.9). The mean serum sodium concentration at 24 hours
      was significantly lower in children receiving the reduced osmolarity ORS solution
      (134 +/- 6 mEq/L) than in children receiving the standard WHO ORS (138 +/- 7
      mEq/L) (p < 0.001). The relative risk of the development or worsening of
      hyponatremia was not increased in children given the reduced osmolarity ORS, and
      urine output was similar in the treatment groups. CONCLUSION: The reduced
      osmolarity ORS has beneficial effects on the clinical course of acute diarrhea in
      children by reducing stool output, and the proportion of children with vomiting
      during the rehydration phase, and by reducing the need for supplemental
      intravenous therapy. These results provide support for the use of a reduced
      osmolarity ORS in children with acute noncholera diarrhea.

PMID- 8551421
TI  - Frequent recurrence and persistence of varicella-zoster virus infections in
      children infected with human immunodeficiency virus type 1.
AB  - OBJECTIVE: To examine complications and treatment of varicella-zoster virus (VZV)
      infections in children infected with human immunodeficiency virus type 1 (HIV-1).
      METHODS: Cases of VZV infection were identified retrospectively by reports to the
      department of health services and review of medical charts. The CD4+ cell counts
      were correlated with severity and frequency of VZV episodes. RESULTS: We
      identified 117 episodes of VZV infection in 73 HIV-1-infected children between
      Aug. 21, 1986, and Dec. 1, 1993. The most common complications were recurrence
      and persistence; 38 children (53%) had 69 recurrent episodes of VZV infection.
      The majority of children (61%) had zoster during the first recurrent episode, and
      32% had a disseminated eruption typical of varicella. There was a strong
      association between an increasing number of episodes of VZV infection and low
      CD4+ cell count (p = 0.0008). In a subgroup followed for at least 2 years after
      their primary varicella episode, 10 of 22 children had a recurrence. Persistence
      of VZV infection was documented in 10 of 73 children, whereas other complications
      were rare. Thirty-three children (45%) were hospitalized and received acyclovir
      intravenously. CONCLUSION: Primary, recurrent, and persistent VZV infections are
      a frequent cause of morbidity and hospitalization for HIV-1-infected children.
      Studies of improved preventive and therapeutic agents are urgently needed in this
      population.

PMID- 8551422
TI  - Natural history of somatic growth in infants born to women infected by human
      immunodeficiency virus. Women and Infants Transmission Study Group.
AB  - OBJECTIVE: To evaluate the nature and magnitude of the effect of congenitally or
      perinatally acquired human immunodeficiency virus (HIV) infection on somatic
      growth from birth through 18 months of age. STUDY DESIGN: Anthropometry was
      performed serially in 282 term infants born to HIV-infected women in a
      multicenter prospective natural history cohort study. Repeated measures analysis
      was used to compare z-score anthropometric indexes of weight-for-age, length-for
      age, weight-for-length, and head circumference-for-age between infected and
      uninfected infants, with adjustment for covariates including infant gender;
      maternal education; prenatal alcohol, tobacco, and/or illicit drug exposure; and
      mean prenatal CD4+ T-lymphocyte count. A separate repeated measures model was
      used to assess the effect of infant zidovudine treatment on growth. RESULTS:
      Infants infected with HIV were an estimated average 0.28 kg lighter and 1.64 cm
      shorter than uninfected infants at birth, were 0.71 kg lighter and 2.25 cm
      shorter by 18 months of age, and had a sustained estimated average decrement of
      0.70 to 0.75 cm in head circumference. Patterns of growth were similar in male
      and female infants. Infected infants had a progressive decrement in body mass
      index from birth through 6 months of age. Infection with HIV was associated with
      significant decrements across all standardized growth outcome measures after
      adjustment for covariates. Mean z scores were lower for weight by 0.612 (p <
      0.001), for length by 0.735 (p < 0.001), for weight-for-length by 0.255 (p =
      0.02), and for head circumference by 0.563 (p < 0.001) SD units compared with
      uninfected infants. Zidovudine treatment was not associated with improved growth.
      CONCLUSION: The effect of congenitally or perinatally acquired HIV infection on
      infant growth is one of early and progressive decrements in attained linear
      growth and growth in mass, early and sustained decrements in head growth, and
      marked early decrements in body mass index.

PMID- 8551423
TI  - Thyroid abnormalities in children infected with human immunodeficiency virus.
AB  - OBJECTIVE: To study thyroid function in children infected with human
      immunodeficiency virus (HIV) and determine whether there are correlates of
      thyroid dysfunction with disease progression. STUDY DESIGN: Total and free
      thyroxine, triiodothyronine, reverse triiodothyronine, thyrotropin, and thyroxine
      binding globulin (TBG) were measured in 167 children with HIV infection (age, 1
      to 19 years; mean, 9.15 years). SETTING: Pediatric Branch, National Cancer
      Institute. RESULTS: Free thyroxine was at or below the lower limit of normal
      (normal, 1.0 to 1.9 ng/dl) in 18% of the children; thyrotropin and TBG levels
      were above the normal range in 31% and 30%, respectively. There was an inverse
      correlation between CD4+ cell count and thyrotropin, and between CD4+ cell count
      and TBG. No correlation was found between thyroid function and other disease
      symptoms or medications. CONCLUSION: These findings indicate that thyroid
      abnormalities occur more frequently in children with HIV infection than was
      previously reported, have a different profile from the thyroid abnormalities
      associated with other chronic disease conditions, and correlate with disease
      progression.

PMID- 8551424
TI  - Mortality rates for patients with a history of Kawasaki disease in Japan.
      Kawasaki Disease Follow-up Group.
AB  - OBJECTIVE: To determine whether the mortality rate of patients with a history of
      Kawasaki disease is higher than that of the general population. DESIGN: In a
      cohort study, 6585 patients with Kawasaki disease were observed from the first
      medical encounter because of the disease through the end of 1992, or until death.
      Standardized mortality ratios (SMRs) with 95% confidence intervals (CI) were
      calculated with vital statistics data of Japan for the control. RESULTS: Of 6585
      patients who met the eligibility criteria, 6550 (99.5%) were followed through
      either the end of the study or the date of death. Nineteen patients (14 male
      subjects) died during the study period; an overall SMR of 1.56 (955 CI, 0.94 to
      2.43) was calculated for the entire study period. The SMR was 1.78 (95% CI, 0.97
      to 2.99) for male subjects and 1.16 (95% CI, 0.38 to 2.71) for female subjects.
      During the acute phase of the disease (the first 2 months after onset), the SMR
      was higher, particularly in male subjects (SMR, 10.12; 95% CI, 3.72 to 22.07).
      After the acute phase, however, both boys and girls had low SMRs. Nine of the 19
      deaths were caused by Kawasaki disease; there were 2 deaths as a result of
      congenital anomalies of the circulatory system and 2 subjects died of malignant
      neoplasms of lymphatic or hematopoietic tissues. CONCLUSIONS: Although the
      mortality rate among those with a history of Kawasaki disease was elevated in
      Japan, many of the deaths that caused the elevation occurred during the acute
      phase of the disease. The mortality rate was not increased after the acute phase
      of the disease.

PMID- 8551426
TI  - A prevalent mutation for galactosemia among black Americans.
AB  - OBJECTIVE: To define the mutation causing galactosemia in patients of black
      American origin who have no galactose-1-phosphate uridyltransferase (GALT)
      activity in erythrocytes but good clinical outcome. METHODS: We discovered a
      mutation caused by a C-->T transition at base-pair 1158 of the GALT gene that
      results in a serine-to-leucine substitution at codon 135 (S135L). We developed a
      method with which to screen populations for its prevalence. We compared galactose
      1-phosphate uridyltransferase among erythrocytes, leukocytes, and transformed
      lymphoblasts, as well as total body oxidation of D-(13C)-galactose to 13CO2 among
      three genotypes for GALT (S135L/S135L, Q188R/Q188R, and Normal/Normal). RESULTS:
      We found a 48% prevalence of the S135L mutation among 17 black American patients
      with classic galactosemia and a 1% prevalence in a population of 50 black
      Americans without galactosemia. The S135L mutation was not found in 84 white
      patients with G/G galactosemia nor in 87 white control subjects without
      galactosemia. We found normal whole body oxidation of D-(13C)-galactose by the
      patient homozygous for S135L and various degrees of enzyme impairment among
      different tissues. CONCLUSIONS: The S135L mutation in the GALT gene is a
      prevalent cause of galactosemia among black patients. Because GALT activity
      varies in different tissues of patients homozygous for S135L, they may have a
      better clinical outcome than patients who are homozygous for Q188R when both are
      treated from infancy.

PMID- 8551425
TI  - Stress and incidence of bleeding in children and adolescents with hemophilia.
AB  - OBJECTIVE: To examine the relationship of stress and incidence of bleeding in
      boys with hemophilia. STUDY DESIGN: We conducted a 6-month longitudinal study of
      97 subjects (ages 4 to 16 years) from six hemophilia centers. Diaries recorded
      bleeding episodes (including site and history of previous trauma) and both child
      and parent daily stress. Parent and child stressful life event measures were
      obtained monthly. Socioeconomic data and clotting factor level were determined at
      enrollment. Logistic regression models examined the influence of recent stress on
      likelihood of bleeding on each day, controlling for factor level and
      socioeconomic data. We also determined associations of aggregated previous
      month's events with bleeding likelihood in the succeeding month. RESULTS: Fifty
      eight percent of study participants had severe hemophilia. The sample population
      averaged nine bleeding episodes per 6 months; of these; two thirds of bleeding
      incidents occurred into joints and 44% after injury. Factor level strongly
      predicted bleeding incidence (p < 0.0001). Increased parent stress was associated
      with increased bleeding in general (odds ratio = 1.37, p < 0.003) and with injury
      (odds ratio = 1.65, p < 0.001), but not bleeding into joints. Similar findings
      followed parent reports of positive life events. Increased parent negative life
      events in 1 month were associated with increased bleeding in the succeeding month
      (p < 0.05). CONCLUSION: Short- and long-term parental stress may lead to
      increased bleeding incidence in hemophilia, although factor level much more
      strongly predicts bleeding.

PMID- 8551428
TI  - Practicing refractive surgery with Food and Drug Administration restraints.

PMID- 8551429
TI  - Arcuate keratotomy for cataract surgery and astigmatism.

PMID- 8551427
TI  - Pneumococcal polysaccharide vaccine in children with chronic renal disease: a
      prospective study of antibody response and duration.
AB  - We studied the antibody response to pneumococcal serotypes 3 and 14 after
      pneumococcal polysaccharide vaccine was administered to 41 children with renal
      disease. One month after vaccination, 76% and 61% of patients achieved at least a
      twofold titer rise to serotypes 3 and 14, respectively; this finding was
      comparable to historic control values. One year after vaccination, the majority
      of patients retained protective antibody levels. Achieving a titer > or = 1.0
      microgram/ml IgG at 1 month was highly predictive of retaining a protective
      antibody level > or = 0.15 microgram/ml at 1 year.

PMID- 8551430
TI  - Wedge resection to treat ectatic dystrophies.

PMID- 8551431
TI  - Descemet's detachment repair.

PMID- 8551432
TI  - Vancomycin-resistant enterococci.

PMID- 8551433
TI  - Consultation section. Cataract surgery.

PMID- 8551434
TI  - Nonpenetrating trabeculectomy with placement of a collagen drainage device.
AB  - Since the advent of trabeculectomy with antimetabolite therapy, there have been
      few changes in the surgical management of glaucoma. This is the first report of a
      new technique, nonpenetrating trabeculectomy with placement of a collagen
      drainage device. The procedure facilitates aqueous drainage without entering the
      human eye. Meticulous surgical dissection of the trabecular meshwork is required
      with creation of an external filtration tract and subscleral positioning of a
      collagen device to facilitate aqueous drainage. With this procedure, the surgeon
      can avoid common complications of glaucoma surgery such as synechias,
      overfiltration, hypotony, intraocular infection, uveal prolapse, and failed
      surgical blebs. The procedure and device have been used extensively in Russia.

PMID- 8551435
TI  - Capsulotomy for phacoemulsification in hypermature cataracts.
AB  - We describe a modified surgical technique of anterior capsulotomy and
      phacoemulsification for use in hypermature cataracts. Surgical steps included
      inferior linear capsulotomy with aspiration of milky cortex, inflation of the
      capsular sac with viscoelastic, a reverse triangular anterior capsulotomy with
      Vannas scissors, and in-the-bag bimanual sculpting of the nucleus. An oval 5 mm x
      6 mm posterior chamber intraocular lens was used with single horizontal or no
      stitch wound closure. The technique was used successfully in 20 cases of
      hypermature cataract. The mean time required to perform phacoemulsification was
      3.46 minutes (range 1.2 to 6.3 minutes), with a standard deviation of 1.29.
      Visual acuity on the first postoperative day ranged from 20/20 to 20/60 (median
      20/40). At one week, the mean astigmatism was 1.01 diopters (range 0.25 to 2.75
      diopters). The mean endothelial cell loss was 13% (range 3.6% to 26.0%). Based on
      our results, the modified phacoemulsification technique merits consideration for
      use in hypermature cataracts.

PMID- 8551436
TI  - Intraoperative semiquantitative keratometry using the keratoscopic astigmatic
      ruler.
AB  - Intraoperative keratometry enables the surgeon to set an appropriate amount of
      corneal astigmatism with the suture tension. Errors in estimating or measuring
      the astigmatism can occur with hand-held keratometers because the distance an
      object is held from an astigmatic cornea influences the shape of the elliptical
      image. Thus hand-held instruments should be held at a calibrated distance. We
      have designed a new hand-held keratometer, the keratoscopic astigmatic ruler, to
      assess the magnitude of corneal astigmatism. It consists of a rack of elliptical
      keratoscopic lenses corresponding to increasing magnitudes of astigmatism and is
      made from inexpensive autoclavable injection-molded plastic. The ruler's
      keratoscopic lenses refract light, creating a real aerial image above the cornea
      that produces a bright and easily determined corneal reflection. The ruler
      incorporates a sight to allow the user to hold the ruler at the correct distance.

PMID- 8551437
TI  - Healing of reopened-and-sutured radial keratotomy wounds.
AB  - We designed a study to evaluate healing in reopened-and-sutured (RAS) keratotomy
      wounds to determine the efficacy of reoperations in treating radial keratotomy
      overcorrections. Using light and transmission electron microscopy, we compared
      stromal scar tissue organization (transverse fibroblast orientation and collagen
      fiber continuity across the wound) in RAS wounds and in sutured and unsutured
      control wounds in 18 monkey eyes one to nine weeks after surgery. Wound healing
      morphology of RAS wounds varied with the interval between reoperation and
      termination of the experiment. Scar tissue organization was sagittal at one week
      postoperatively, transverse in the anterior and mid regions after four weeks, and
      transverse over the entire wound after nine weeks. Sutured wounds showed a
      similar pattern of healing, although transverse scar tissue organization was
      restricted to the anterior and mid regions in the late healing phases. In
      contrast, unsutured wounds showed a temporary, transverse scar tissue
      organization over the entire wound depth at two to four weeks and a progressive
      reorientation of the mid and posterior scar tissue sagittal to the wound at later
      intervals. The results suggest that reopening and suturing keratotomy incisions
      to treat radial keratotomy overcorrections may be effective through a myopic
      shift induced by sutured wound apposition and long-term wound remodeling,
      contraction, or both.

PMID- 8551438
TI  - Intraoperative corneal pachymetry in eyes having radial keratotomy.
AB  - We prospectively studied 45 eyes that had radial keratotomy for correction of
      myopia to determine whether significant changes in corneal thickness occurred
      during the surgical procedure and which paracentral corneal region was the
      thinnest consistently. We used a standard bidirectional technique with a diamond
      knife. The inferotemporal paracentral region was the thinnest most frequently
      (38% of eyes) both pre-incision and post-incision. However, each of the other
      paracentral regions measured the thinnest in a smaller percentage of eyes:
      temporal (28% pre-incision and post-incision); inferior (19% pre-incision, 21%
      post-incision); nasal (11% pre-incision, 9% post-incision); superior (4% pre
      incision and post-incision). A statistically significant reduction in corneal
      thickness occurred intraoperatively in all regions.

PMID- 8551439
TI  - Photorefractive keratectomy in pediatric patients.
AB  - This article reports the results of photorefractive keratectomy in nine patients
      between 10 and 15 years of age who were treated for the following refractive
      errors: unilateral myopia, post intraocular lens myopia, and unequal
      hypermetropia with amblyopia. Visual acuity improved and spectacle correction
      decreased in all patients. There was significant visual improvement with pleoptic
      treatment in one amblyopic hypermetropic patient.

PMID- 8551440
TI  - Multizone/multipass photorefractive keratectomy: six month results.
AB  - A multizone/multipass photorefractive keratectomy (MP-PRK) technique was used to
      treat 315 eyes with the 193 nm VISX 20/20 excimer laser. Algorithms were
      developed to treat the full range of myopia, including 170 low myopic eyes (-1.0
      to -6.0 diopters [D]), 105 moderately myopic eyes (-6.0 to -10.0 D), and 40
      highly myopic eyes (-10.0 to -27.0 D). Preoperative mean myopia was -6.69 D;
      astigmatism equal to or greater than -0.5 D (mean -1.18 D) was present in 193
      eyes. At one month postoperatively, most eyes were slightly hyperopic (mean +0.8
      D); this regressed to a mean of -0.16 D. At six months, 95.5% of low myopes,
      84.8% of moderate myopes, and 59.5% of high myopes were within 1.0 D of
      emmetropia; 78.4% of high myopes were within 2.0 D of the intended correction.
      There was no loss of 20/40 best corrected visual acuity (BCVA) at six months; a
      significant gain in 20/25 BCVA was seen in the moderate and high myopia groups (P
      < .05). At six months, uncorrected visual acuity was 20/25 in 89.4% of low
      myopes, 75.0% of moderate myopes, and 25.7% of high myopes. Mean haze value was
      0.48 at one month and was not significantly different among the three groups
      (0.44, 0.52, 0.51, respectively). A control group treated with the one-pass
      multizone technique had a significantly higher amount of haze: 1.05 (P < .01).
      The data presented compare favorably with those obtained from other centers.
      Based on these results, we believe that MP-PRK is a safe, reliable technique to
      correct most low, moderate, and high myopia.

PMID- 8551442
TI  - Intraocular pressure response to combined phacoemulsification and trabeculotomy
      ab externo versus phacoemulsification alone in primary open-angle glaucoma.
AB  - We investigated trabeculotomy ab externo as a means of optimizing intraocular
      pressure (IOP) control in glaucoma patients having phacoemulsification and
      implantation of an intraocular lens (IOL). A prospective, randomized, controlled
      study was performed to evaluate the effect on IOP and the incidence of
      complications associated with combined phacoemulsification and trabeculotomy ab
      externo. The study group had the combined procedure, while the control group had
      only phacoemulsification with IOL implantation. A total of 106 patients were
      randomized, and the IOP for each group was compared at 3, 6, 12, and 24 months.
      At two years, the mean IOP reduction was 6.1 mm Hg in the study group and 3.8 mm
      Hg in the control group (P = .001). There were no complications in the control
      group. Two complications (2/53 or 3.8%) occurred in the study group: a small tear
      in Descemet's membrane and a postoperative microhyphema. There was no increase in
      medication in either the study or control group. Combined phacoemulsification and
      trabeculotomy ab externo represents an option to lower IOP and potentially reduce
      the need for pressure-lowering medications in patients with primary open-angle
      glaucoma and visually significant cataracts.

PMID- 8551441
TI  - Clinical results of excimer laser photorefractive keratectomy: a multicenter
      study of 265 eyes.
AB  - Efficacy, predictability, and safety of excimer laser photorefractive keratectomy
      were evaluated at centers in Paris and Brest, France. Photoablation was performed
      with the VISX laser on 265 eyes (151 at the Paris center and 114 at the Brest
      center). The eyes were clinically and statistically evaluated over a six month
      follow-up. Initial myopia ranged from -0.7 to -19.4 diopters (D) (mean spherical
      equivalent [SE] -5.9 D) in the Paris center and from -0.9 to -14.5 D (SE -4.5 D)
      in the Brest center. At both centers, the mean uncorrected visual acuity was
      worse than 20/200; over 90% of cases in each center had a best uncorrected visual
      acuity of 20/100 or worse. Results are reported globally and for subgroups of
      myopia: Group A, SE better than or equal to -3.0 D; Group B, SE worse than -3.0 D
      and better than or equal to -7.0 D; Group C, SE worse than -7.0 D. Uncorrected
      visual acuity was significantly improved in the patients followed for six months;
      64% of Paris cases and 62% of Brest cases obtained an uncorrected visual acuity
      of 20/40 or better. Predictability of the treatment was good; 67% of Paris eyes
      and 74% of Brest eyes were less than 1.0 D from the intended correction after six
      months. The data suggest that the initial myopia affected the efficacy and
      predictability of the treatment; results in the mild to moderate myopia eyes were
      significantly better than results in the severe myopia eyes. One case of visual
      acuity regression (less than one line) was observed in the two groups. This was
      associated with corneal haze of moderate intensity.

PMID- 8551443
TI  - Complications and results of phacoemulsification performed by residents.
AB  - The use of phacoemulsification by ophthalmic surgeons has increased markedly over
      the past five years. Previous studies have reported relatively high rates of
      vitreous loss by residents learning phacoemulsification. We retrospectively
      analyzed the complications and results in 300 cases of phacoemulsification with
      intraocular lens implantation performed by residents. The first 40 cases done by
      four residents in their second year of training were compared with approximately
      the last 40 cases done by each resident at the end of the third year. The overall
      rate of surgical complications was 6.3%, and the total rate of vitreous loss was
      3.3%. The rate of surgical complications during the initial surgeries in the
      second year of residency was 9.3%; it was 3.3% by the end of the third year. The
      rate of vitreous loss was 5.3% in the second year and 1.3% during the third year.
      Postoperatively, 90.6% of all eyes had a final best corrected visual acuity of
      20/40 or better (95% excluding patients with pre-existing ocular disease). With
      proper training and supervision, the rate of surgical complications for residents
      learning phacoemulsification is acceptably low when compared with the rate of
      extracapsular cataract extraction.

PMID- 8551444
TI  - Drop, then decide approach to topical anesthesia.
AB  - I developed an approach to topical anesthesia--drop, then decide--with the goal
      of increasing the percentage of patients able to have topical anesthesia for
      anterior segment surgery. This study comprised 150 consecutive surgeries
      performed using the technique, including cataract extraction with intraocular
      lens (IOL) implantation, trabeculectomy, combined procedures, and McCannel
      suturing. Six patients also had anterior vitrectomy. Patients were not
      preselected. All cases were initiated with topical anesthesia and supplemented
      with at least mild intravenous sedation by an anesthesiologist. The decision on
      whether to use anesthetic blocks was made after evaluating patient response early
      in the surgery. The approach had an overall success rate (no regional block
      needed) of 89.3%; 92.0% of the cataract/IOL implantation cases were successful.
      Most patients reported they were comfortable throughout the procedure. The
      success rate was high among patients who may be considered poor candidates for
      topical anesthesia; younger patients had more difficulty. This approach allows
      more patients to benefit from the advantages of topical anesthesia over other
      techniques.

PMID- 8551445
TI  - Topical anesthesia for phacoemulsification: initial 20-case series with one month
      follow-up.
AB  - We report the results of our initial 20 phacoemulsification cases performed using
      topical anesthesia. The preferred topical regimen consisted of preservative-free
      0.75% bupivacaine. Intravenous sedation was provided primarily with fentanyl and
      midazolam. Phacoemulsification was performed through a scleral tunnel incision,
      and a one-piece poly(methyl methacrylate) or three-piece silicone intraocular
      lens was implanted. There were no complications with the anesthetic technique.
      One day postoperatively, 69% of patients with a desired refractive error within
      0.75 diopters of emmetropia had an uncorrected visual acuity of 20/40 or better.
      At one month, all patients had a best corrected acuity of 20/30 or better, and
      60%, 20/20 or better. Eighteen patients reported complete intraoperative comfort,
      and 17 reported complete postoperative comfort. Seven of the 10 patients who had
      had previous peribulbar anesthesia preferred topical. All 10 "first eye" patients
      said they would choose topical anesthesia for future surgery. With appropriate
      case selection, topical anesthesia for phacoemulsification surgery can be used
      with excellent intraoperative and postoperative results.

PMID- 8551446
TI  - Intraocular pressure seven years after extracapsular cataract extraction and
      sulcus implantation of a posterior chamber intraocular lens.
AB  - Seven years after extracapsular cataract extraction (ECCE) and sulcus
      implantation of a posterior chamber intraocular lens, we measured the intraocular
      pressure (IOP) in 28 eyes of 28 patients. The results were compared with the
      preoperative IOP and with the postoperative IOP at four months and 2 1/2 years.
      The mean IOP value seven years after surgery was 1.3 mm Hg lower than the
      preoperative mean value. No significant difference was found among the values at
      four months, 2 1/2 years, and seven years. One patient experienced a marked rise
      in IOP between 2 1/2 years and seven years and was excluded from the
      calculations. However, we could not tell whether it was a consequence of the
      cataract surgery. In this study, we found that IOP stabilized at a postoperative
      level that was significantly lower than the preoperative value and has remained
      there for seven years.

PMID- 8551447
TI  - Intraocular lens removal from eyes with chronic low-grade endophthalmitis.
AB  - Intraocular lenses (IOLs) were removed from 11 eyes with chronic low-grade
      endophthalmitis after cataract extraction to restore useful vision and prevent
      recurrence. One anterior chamber lens, one iris-supported lens, and nine
      posterior chamber lenses were removed. In the eyes with posterior chamber lenses,
      the posterior capsule was intact; total (n = 7) or partial (n = 2) capsulectomy
      was performed in these eyes. Aqueous humor specimens obtained at surgery were
      positive for bacteria in five eyes, but scanning electron microscopy showed
      bacteria on all removed IOLs and capsular bags. Final best corrected visual
      acuity was 20/40 or better in seven eyes. Reduced visual acuity, between 20/50
      and 20/400 in three eyes and counting fingers in one eye, was related to retinal
      detachment (n = 2) and age-related macular degeneration (n = 2). Transient
      hyphema was seen in one eye. With a mean follow-up of 21 months (range 10 to 31
      months), no recurrence of inflammation was observed. The results show that
      negative cultures do not preclude a bacterial cause for infection and that
      primary IOL removal with partial or total capsulectomy provides a surgical
      approach to the treatment of chronic low-grade endophthalmitis not responsive to
      medical therapy.

PMID- 8551448
TI  - Moisture droplet formation on the posterior surface of intraocular lenses during
      fluid/air exchange.
AB  - We investigated the conditions under which moisture droplets would form on
      intraocular lens (IOL) posterior surfaces during fluid/air exchange procedures in
      rabbits implanted with silicone or poly(methyl methacrylate) (PMMA) IOLs.
      Moisture droplets did not form when the posterior capsule was intact, regardless
      of IOL material or infusion fluid temperature. If a capsular tear was present,
      droplets formed with both IOL materials when balanced salt solution (BSS) at
      ambient temperature was used as the infusion fluid. This effect was significantly
      more pronounced with silicone IOLs, resulting in an immediate loss of
      visualization of the fundus. In these cases, visualization was quickly restored
      by applying a viscoelastic to the posterior IOL surface.

PMID- 8551449
TI  - Spherical aberration and glare disability with intraocular lenses of different
      optical design.
AB  - We implanted several kinds of intraocular lenses (IOLs), calculated the spherical
      aberration using a computed ray-tracing system, and investigated the correlation
      between glare disability and spherical aberration and the difference in glare
      disability among the different IOL types. Type A IOLs (convex-plano), except for
      those with high power, had the smallest spherical aberration. Type B IOLs
      (biconvex, anterior more curved) had the smallest spherical aberration at high
      power. Type D IOLs (biconvex, posterior more curved) had the largest spherical
      aberration. The correlation between glare disability and spherical aberration was
      statistically significant for types A, B and C (equiconvex) IOLs. There was no
      correlation between glare disability and spherical aberration for Type D IOLs,
      although they showed the smallest glare disability of the four types. These
      results indicate that the spherical aberration of an IOL, which is calculated by
      an optical design program, may be a good criterion for selecting an IOL design.

PMID- 8551450
TI  - Effect of intraocular lens design on posterior capsule opacification after
      continuous curvilinear capsulorhexis.
AB  - We compared the effect of biconvex and convex-plano (posterior plano) intraocular
      lenses on posterior capsule opacification (PCO) following continuous curvilinear
      capsulorhexis (CCC) in 212 eyes. During the three years following surgery, the
      cumulative frequency of neodymium:YAG laser posterior capsulotomy, calculated
      with the Kaplan-Meier method, was significantly higher in patients in the
      biconvex group (32.5% by the third year) than in those in the convex-plano group
      (5.9% by the third year) (P < .05, Wilcoxon's test; P < .01, Cox-Mantel's test).
      Measured with the tracing method, the area within a 5 mm diameter central circle
      that developed Elschnig pearls was 2.93 +/- 4.91 mm2 in the biconvex group and
      1.66 +/- 2.37 mm2 in the convex-plano group. In the study, PCO was less severe in
      the convex-plano group than in the biconvex group following CCC. These results
      are contrary to those reported previously in patients with can-opener
      capsulotomy.

PMID- 8551451
TI  - Corneal endothelial cell loss caused by detached opacified anterior lens capsule
      in the anterior chamber.
AB  - From 1984 to 1986, we performed cataract surgery through a 1.5 mm anterior
      capsule hole in 77 eyes. The hole was enlarged to 6.0 mm by a slit incision, and
      an intraocular lens was implanted into an almost completely intact capsular bag.
      Twelve (16%) eyes developed severe postoperative anterior capsule opacification.
      The opacified central anterior capsule, approximately 5 mm in diameter, was
      detached by can-opener anterior capsulotomy using a neodymium:YAG laser and fell
      into the inferior anterior chamber. Inferior corneal endothelial cell loss
      occurred in nine of the 12 eyes within 20 months after detachment; in six of the
      nine, inferior corneal endothelial cell density decreased 50% more than central
      cornea cell density. This method will be unsuitable for treating the extensive
      anterior capsule opacification that will occur when endocapsular cataract surgery
      that retains most of the lens capsule is widely performed in the future.

PMID- 8551452
TI  - Effect of cataract surgery on aqueous turnover and blood-aqueous barrier.
AB  - We evaluated changes in aqueous outflow and blood-aqueous barrier (BAB)
      disruption after cataract surgery in two randomly selected groups of eyes. In one
      group, a high-viscosity viscoelastic was used for intraocular lens (IOL)
      implantation; in the other, a low-viscosity viscoelastic. Fluorophotometry was
      used to evaluate aqueous humor dynamics five to seven hours after IOL
      implantation. Aqueous outflow after IOL implantation in operated eyes was nearly
      twice that in the fellow eyes, which served as controls. Mean protein
      concentration in the anterior chamber was also elevated in operated eyes.
      However, postoperative aqueous outflow did not differ significantly between the
      two groups. The substantial increase in aqueous outflow observed postoperatively
      and the increase in aqueous humor protein concentration were closely related to
      BAB disruption. These results suggest that BAB disruption may be a main cause of
      the transient high intraocular pressure observed after IOL implantation in both
      groups.

PMID- 8551453
TI  - Healon GV versus Healon in demanding cataract surgery.
AB  - This study compared how well two sodium hyaluronate viscoelastics maintained the
      anterior chamber during cataract surgery in eyes at risk for high vitreous
      pressure. Patients were divided into two groups based on the sodium hyaluronate
      used: Healon or Healon GV. Qualitative data were obtained with a digital slide
      gauge attached to the operating microscope. After capsulorhexis, mean anterior
      chamber depth (distance of the corneal apex to the iris plane) was significantly
      greater in the Healon GV group (P = .0012). Subjective intraoperative evaluation
      by surgeons also favored Healon GV. There was no difference between the groups in
      postoperative inflammation, corneal edema, intraocular pressure, or visual
      acuity. Therefore, although the two viscoelastics are equally safe, Healon GV
      maintains the anterior chamber better during cataract surgery.

PMID- 8551454
TI  - Management of Descemet's membrane detachment.
AB  - Detachment of Descemet's membrane is a rare but serious complication of cataract
      surgery. Most surgeons attempt to reposition the membrane by injecting air, slow
      reabsorbing gases, or viscoelastic substances into the anterior chamber. We
      describe five cases of subtotal detachment without rolled scroll. These cases
      recovered spontaneously after two to three months. We believe that conservative
      treatment in such cases is indicated and has a good chance of favorable outcome.

PMID- 8551455
TI  - The categorization of thought disorder.
AB  - We describe the development of a new system for categorizing thought disorder. In
      the development phase (Study 1), we examined the degree to which speech samples
      and definitions of thought disorder subtypes taken from: (1) the Scale for the
      Assessment of Thought, Language, and Communication (TLC); (2) the Thought
      Disorder Index (TDI); and (3) the Assessment of Bizarre-Idiosyncratic Thinking
      (BIT), reflected disturbances in form versus disturbances in content. Ratings
      were provided by naive judges, experienced clinicians, and linguistic experts.
      The results contributed to the development of a new system dividing thought
      disorder into disturbances in (1) fluency, (2) discourse coherence, (3) content,
      and (4) social convention. In the validation phase (Study 2), 21 schizophrenic
      and 19 manic subjects were interviewed, interpreted proverbs, and responded to
      Rorschach cards. Subjects' speech was rated using the TLC, TDI, and BIT. We also
      measured hallucinations, delusions, and digit span performance. The results of
      Study 2 provided evidence supporting the validity of our new categorization
      system.

PMID- 8551456
TI  - The effectiveness of community water fluoridation: beyond dummy variables for
      fluoride exposure.

PMID- 8551457
TI  - ["Brief Communications" feature in the Journal of Public Health Dentistry].

PMID- 8551458
TI  - Factors affecting self-ratings of oral health.
AB  - OBJECTIVES: The purpose of this study is to determine the relationship of self
      rated oral health to a comprehensive battery of clinical, sociodemographic,
      physical health, and mental health measures in a well-elderly urban population.
      METHODS: Results are based on telephone interviews and clinical assessments of
      550 subjects over 65 years of age participating in a Los Angeles-based Medicare
      project during 1990. Subjects were mostly female, white (89%), with above-average
      income. RESULTS: Findings show that: (1) the DMF measure is not as strongly
      related to self-rated oral health as was a single measure of missing teeth; (2)
      the major predictors of self-rated oral health were "worry about teeth" and
      "appearance of teeth" followed by total missing teeth, race, education, and
      depression scores; and (3) self-rated general health is related to self-rated
      oral health. CONCLUSION: Self-rated oral health may be, for older adults, a
      better measure of "health" than of "morbidity".

PMID- 8551459
TI  - Differences between racial groups in the impact of oral disorders among older
      adults in North Carolina.
AB  - OBJECTIVES: This study investigated variations in impact of oral disorders
      between older black adults and older white adults living in North Carolina.
      METHODS: Using the Oral Health Impact Profile (OHIP) questionnaire, 440
      participants aged 70 and older provided data on their perceptions of the impact
      of oral disease on aspects of their lives during the previous 12 months. RESULTS:
      For 22 of the 49 items queried in the OHIP questionnaire, older blacks reported
      more frequent impact than older whites (P < .05). For none of the OHIP items did
      whites report more frequent impact. The impacts reported were diverse and
      included items reflecting pain, physical disability, psychological disability,
      and social disability. When the number of items occurring fairly often or very
      often were summed for dentate participants, blacks reported more items than did
      whites (3.7 vs 1.1, P < .0001). This difference decreased to 2.7 vs 2.0 (P <
      .346) after controlling statistically for greater mean periodontal pocket depth,
      more unreplaced missing teeth, and more episodic dental visits among blacks.
      CONCLUSIONS: Older dentate blacks reported more impact from oral problems than
      older dentate whites. The differences in reported impact likely are linked to
      differences in oral status and dental visit history between these two racial
      groups in North Carolina.

PMID- 8551460
TI  - Dental care satisfaction: the reliability and validity of the DSQ in a low-income
      population.
AB  - OBJECTIVES: Studies examining satisfaction with dental health care among the poor
      are quite rare. This study was done to confirm the internal structure and
      reliability of the Dental Satisfaction Questionnaire (DSQ), a measure of dental
      care satisfaction, among a low-income population, and provide normative data
      regarding dental satisfaction among low-income people. METHODS: Subjects were 895
      mothers of school-aged children who were administered the DSQ as part of a larger
      study of dental utilization and dental fears in Seattle. RESULTS: Factor analysis
      largely confirmed the factor structure of the DSQ. Results also suggested
      subjects in this sample were less satisfied with pain management than nonpoor
      people. Self-reported dental health and dental appearance were associated with
      satisfaction with pain management, quality of care, access to care, and overall
      satisfaction. Race/ethnicity, education level, marital status, nation of origin,
      and type of insurance predicted differences in satisfaction with pain management
      and access. CONCLUSIONS: Barriers to dental care and quality of care among low
      income populations are discussed. Uses and research with the DSQ are suggested.

PMID- 8551461
TI  - Associations between exposure to fluoridated drinking water and dental caries
      experience among children in two Australian states.
AB  - OBJECTIVES: This study assessed associations between exposure to fluoride in
      water and dental caries experience among children in two Australian states.
      METHODS: Cross-sectional data were obtained from 9,690 South Australian children
      aged 5-15 years and 10,195 Queensland children aged 5-12 years. School dental
      service practitioners recorded DMFS and dmfs data. A questionnaire to parents
      gained information about residential history that was used to calculate
      children's percent of lifetime exposed to fluoridated water. RESULTS: Greater
      exposure to fluoride in water was associated with lower dmfs and DMFS in both
      states (P < .01), although in South Australia the effect for DMFS was
      statistically significant only after controlling for extent of unknown
      fluoridation exposure and for fluoride supplements. Caries-fluoridation
      associations were stronger for dmfs compared with DMFS and for Queensland (5% of
      population fluoridated) compared with South Australia (70% of population
      fluoridated). Effects for DMFS persisted after controlling for socioeconomic
      factors. CONCLUSIONS: Fluoridation was associated with lower caries experience.
      The weaker association with DMFS in South Australia may be due to less caries and
      more fissure sealants in that state, and is consistent with a "diffusion" effect,
      whereby a high proportion of the population exposed to fluoridation diminishes
      differences among exposure groups.

PMID- 8551462
TI  - Treatment and posttreatment effects of fluoride mouthrinsing after 17 years.
AB  - OBJECTIVES: This study assessed the treatment and posttreatment effects of a
      school-based, fluoride mouthrinse regimen. METHODS: Children in a nonfluoridated
      community in Japan participated in a daily rinse program using a 0.05 percent NaF
      solution in nursery and primary schools, and a weekly rinse with 0.2 percent NaF
      in junior high school. Students were examined at least annually for dental caries
      and dental treatment was provided in a public dental clinic through the ninth
      grade. Incipient carious lesions with no cavitation were not restored. RESULTS:
      The percent of children in grades one through nine (6-14 years of age) with
      caries-free permanent teeth increased from 13.4 percent in 1974 to 73.0 percent
      in 1991, while the mean DMFT decreased by 86 percent during this period. For 12
      year-olds, mean DMFT scores declined to about one tooth per child after 1982. For
      adults 20 years of age, there was a 64 percent difference in DMFS between the
      treatment group who started the rinse regimen at 4 years of age and continued for
      11 years, and the controls who lived in different districts and did not
      participate in a fluoride rinse regimen. CONCLUSIONS: Children who began rinsing
      at 4 or 5 years of age benefited the most from the program. The program was
      inexpensive, simple to implement and well accepted by families and teachers. The
      conservative treatment policy in the public clinic likely contributed to the
      benefits derived by participants.

PMID- 8551463
TI  - Dental caries-reducing effects of a milk fluoridation project in Bulgaria.
AB  - OBJECTIVES: The aim of the present study was to investigate the effects of a
      community-based milk fluoridation project on dental caries. METHODS: Fluoridated
      milk was provided to about one-half of kindergarten and other schoolchildren in
      Asenovgrad, a town in the southern part of Bulgaria. The estimated daily milk
      consumption was 200 ml containing 1 mg of fluoride (approximately 5 ppm F). Cross
      sectional samples of 6 1/2-year-olds in Asenovgrad and Panaguriche (a nearby town
      selected as the reference community) were examined at the start of the study in
      1988 and after three years. Additional cross-sectional samples of 7 1/2-year-olds
      in Asenovgrad who were and were not drinking fluoridated milk were examined at
      baseline and at three years to provided an internal control group. Samples of 6
      1/2 and 8 1/2-year-olds from Asenovgrad and Karlovo were examined in 1993 to
      provide for five-year follow-up comparisons. RESULTS: In 6 1/2-year-old children
      who had consumed fluoridated milk for three years, there was a decrease in the
      mean dmft per child of 40 percent and in the mean DMFT of 89 percent compared to
      children examined at baseline. Children in Asenovgrad who were 4 1/2 years old at
      the start of the study and had been drinking fluoridated milk for three years had
      on average 44 percent fewer dmft and 83 percent fewer DMFT at 7 1/2 years of age
      than those not drinking fluoridated milk. After five years the dmft index was 40
      percent less and the DMFT index 79 percent less in those children who had
      participated in the full five years of the program compared to the control group.
      CONCLUSIONS: Results seem to confirm the caries-reducing effects of milk
      fluoridation found in previous studies. Unexpected large caries reductions
      obtained in this nonexperimental study, however, probably cannot be attributed to
      the fluoridation of milk alone. The mere introduction of the project might have
      led to other changes affecting dental caries, such as improved oral hygiene and
      better dietary habits.

PMID- 8551464
TI  - Refining the estimate of the critical period for susceptibility to enamel
      fluorosis in human maxillary central incisors.
AB  - PURPOSE: The purpose of this study was to determine an improved estimate of the
      critical period for susceptibility to fluorosis in human maxillary central
      incisors. METHODS: The fluorosis score, S, of the incisal (I), middle (M), and
      cervical (C) third divisions on the labial surface of right maxillary central
      incisors of subjects (a representative sample of 1,085 Hong Kong Chinese children
      aged 7 to 12 years surveyed in 1986) was determined according to the
      Chronological Fluorosis Assessment (CFA) Index. Subject data were grouped by
      month of birth relative to June 1978, when the designated concentration for
      waterborne fluoride in the community water supply was reduced from 1.0 to 0.7
      mg/L. The analytical task was one of finding the correlation maximum in a system
      of 12 variates and adjustable parameters including the waterborne fluoride
      concentration, [F-], and the fluorosis score. RESULTS: The main findings were:
      (1) the peak correlation of S vs [F-] for the male incisal third centered at 17.5
      months after birth; (2) and six months later for females; (3) the correlation of
      S with [F-] is maximized for S(M) following S(I) by two months, and S(C)
      following S(M) by a further two months for both males and females; and (4) the
      critical period for exposure to fluoride is of about four months' duration for
      each third. CONCLUSIONS: The maxillary central incisor, as a whole, appears most
      at risk to fluorosis from dietary fluoride between age 15 and 24 months for males
      and between 21 and 30 months for females.

PMID- 8551466
TI  - Modification of the Miya hook in vaginal colpopexy.
AB  - OBJECTIVE: To evaluate a modification of the Miya hook in performing vaginal
      sacrospinous ligament fixation. STUDY DESIGN: The modification was performed in
      over 50 patients. It involves placing the needle through the ligament unloaded;
      then the hook is back-threaded with the appropriate suture. The hook is then
      withdrawn, bringing the suture with it. RESULTS: There were no complications as a
      result of this modification. The technique was faster, used fewer instruments and
      obviated fraying of the suture. It could also be adapted when retrieving the
      suture when the classic technique proved difficult. CONCLUSION: The ease of this
      modification should promote the use of this instrument in performing vaginal
      sacrospinous ligament fixation.

PMID- 8551465
TI  - Relative contribution of caries and periodontal disease in adult tooth loss for
      an HMO dental population.
AB  - OBJECTIVES: This study examined the reasons for tooth loss in an adult population
      with dental insurance. METHODS: Computerized records were used to identify Kaiser
      Permanente Dental Care patients aged 40-69 years who had an extraction during
      1992 (n = 1,877). A random sample of 839 dental charts were reviewed. RESULTS:
      Slightly more than 51 percent of the teeth were extracted for periodontal
      disease, 35.4 percent for caries, 9.5 percent for a combination of the two, and
      3.5 percent for other reasons. When considering patients as the unit of analysis,
      58.4 percent of the patients had an extraction for caries, 39.9 percent for
      periodontal disease, 5.0 percent for both, and 2.6 percent for other reasons.
      CONCLUSIONS: In this population both caries and periodontal disease play a role
      in tooth loss. For this reason, prevention programs focusing on the prevention of
      both disease processes should be developed for adults.

PMID- 8551467
TI  - Hysteroscopically detected asymptomatic mullerian anomalies. Prevalence and
      reproductive implications.
AB  - OBJECTIVE: To assess the prevalence of uterine anomalies and relative
      reproductive function in 322 women with abnormal uterine bleeding (AUB) evaluated
      by diagnostic hysteroscopy. STUDY DESIGN: Uterine contours were classified as
      septate/bicornuate, arcuate or normal on the basis of hysteroscopy. A complete
      medical history was obtained from all the subjects; it included a questionnaire
      on menstrual characteristics, reproductive history and pregnancy outcome.
      Cumulative birth rates, frequency of spontaneous abortion, preterm delivery,
      malpresentation and mode of delivery in patients with normal and abnormal uteri
      were compared using life table analysis, the log-rank test and chi 2 analysis.
      RESULTS: Arcuate, septate/bicornuate and unicornuate uteri were observed in 6.5%,
      3.7% and 0.3% of women, respectively. Although 24-month pregnancy rates and
      monthly fecundability rates were similar in women with and without mullerian
      anomalies, the 36-month cumulative live birth rate was significantly lower in
      women with a septate/bicornuate uterus. Overall, women with uterine malformations
      showed a significantly higher miscarriage rate (P < .05) and a significantly
      lower term delivery rate (P < .05) than women with a normal-shaped uterus.
      CONCLUSION: Diagnostic hysteroscopy in women with AUB detected a 10% prevalence
      of uterine anomalies, which were associated with a significantly higher incidence
      of spontaneous abortion and lower cumulative live birth rates.

PMID- 8551468
TI  - First-trimester pancreatitis. Maternal and neonatal outcome.
AB  - OBJECTIVE: To determine the incidence and maternal-fetal outcome of first
      trimester pancreatitis at one institution. STUDY DESIGN: A retrospective study of
      pancreatitis presenting during the first trimester of pregnancy over a 10-year
      period at Magee Womens Hospital. RESULTS: There were 11 cases, for an incidence
      of 0.1/1,000 live births. There was no maternal mortality. Three patients elected
      voluntary termination, and eight pregnancies proceeded to term. All delivered at
      > or = 35 weeks. The mean gestational age was 38.9 +/- 2.1 weeks (mean +/- SD),
      and mean birth weight was 3,103 +/- 641 g. There were no adverse neonatal
      outcomes, although one patient had a fetus with severe intrauterine growth
      retardation. Maternal morbidity and complications were due mainly to gallstone
      pancreatitis, which was the most commonly identified cause of pancreatitis, and
      three patients underwent cholecystectomy during pregnancy or the puerperium. No
      first-trimester pregnancy terminations were performed for medical indications.
      Pancreatitis tended to recur during the examined pregnancy (mean number of
      admissions, 2.27 +/- 2.1). CONCLUSION: Patients should be advised of the
      relapsing nature of pancreatitis that presents during the first trimester.
      However, there is a good prognosis for pregnancy outcome.

PMID- 8551469
TI  - Fetal acoustic stimulation as an adjunct to external cephalic version.
AB  - OBJECTIVE: To evaluate fetal acoustic stimulation (FAS) as an adjunct to external
      cephalic version in a midline fetal spine presentation. STUDY DESIGN: Breech
      presentation in a woman presenting for attempted version at 37 weeks' gestation
      with a fetus in a midline position and the spine anterior is difficult to convert
      to a vertex. An evaluation of FAS to assist in repositioning the fetus in a more
      spine lateral position was carried out. Patients with a failed version attempt
      and a midline breech presentation were enrolled in the study. The patient served
      as her own control. If that attempt failed, an electrolarynx device was used to
      produce a one- to three-second stimulus, and then another version attempt was
      made. RESULTS: Sixteen patients were enrolled. Prior to FAS, 0/16 fetuses were
      successfully turned. FAS altered the position in 100% of patients from spine
      midline to lateral. After FAS, 15/16 (94%) were successfully converted to vertex
      presentation. The one patient whose fetus failed to convert also failed her
      second version attempt (P < .0005). CONCLUSION: FAS may improve the opportunity
      for successful external cephalic version in the properly selected candidate with
      a fetus in a midline position with the spine anterior.

PMID- 8551470
TI  - Continence mechanism after colpo-needle suspension for stress urinary
      incontinence.
AB  - OBJECTIVE: To determine the mechanism by which continence is restored following
      the colpo-needle suspension procedure. STUDY DESIGN: During 1990-1991, 37 women
      underwent colpo-needle suspension for stress urinary incontinence. Urodynamic
      investigation was performed preoperatively and 6-12 months postoperatively, and
      the results of these tests were compared in order to define the changes that
      might be responsible for the restoration of continence. RESULTS: In comparing the
      preoperative and postoperative cystometric and uroflowmetric measurements, we
      found no significant differences in the values for bladder capacity, residual
      volume pressure rise on filling or standing, maximal urethral voiding pressure or
      peak flow rates. The urethral pressure profiles at rest did not result in
      statistically significant differences regarding urethral length or urethral
      pressure. The only such differences postoperatively were elevation of pressure.
      Transmission ratios on coughing and in the proximal half of the urethra were Q1,
      100.3 (P < .001), and Q2, 100.4 (P < .002), respectively. CONCLUSION:
      Colposuspension appears to correct genuine stress incontinence by repositioning
      the proximal urethra in the intraabdominal pressure zone, causing restoration of
      positive pressure transmission to the proximal urethra.

PMID- 8551471
TI  - hRLX-1. In vitro response of human and pig myometrium.
AB  - OBJECTIVE: To study the effect of synthetic h RLX-1 peptide on human and porcine
      myometrium in vitro in comparison to the effect of h RLX-2 peptide. STUDY DESIGN:
      Myometrial strips from humans and pigs in late pregnancy were allowed to
      spontaneously contract in an organ bath. Muscle activity was recorded
      isometrically in response to varying doses of h RLX-1. RESULTS: Synthetic h RLX-1
      peptide at 0.13 micrograms/mL caused sustained and complete inhibition of
      pregnant pig myometrial contractility, comparable to that produced by the h RLX-2
      peptide, showing, for the first time, its biologic activity in this system.
      However, a range of concentrations of h RLX-1 peptide (0.07-7.32 micrograms/mL)
      had no effect on human myometrial contractions in vitro, whereas h RLX-2 peptide
      had some, albeit minimal, activity in this system. CONCLUSION: This result shows
      that h RLX-1 peptide does not appear to be an inhibitor of human myometrial
      activity and that although the pig myometrial relaxin receptor does not appear to
      distinguish between the two human relaxins, the human relaxin receptor might.
      Thus, the control of spontaneous myometrial activity during pregnancy in the
      human appears to be different from that in other species.

PMID- 8551472
TI  - Effect of labor analgesia with nalbuphine hydrochloride on fetal response to
      vibroacoustic stimulation.
AB  - OBJECTIVE: To evaluate the effect of labor analgesia with nalbuphine
      hydrochloride on the fetal response to vibroacoustic stimulation. STUDY DESIGN:
      The response to fetal acoustic stimulation (FAS) was recorded in 27 laboring
      patients before analgesia. After analgesia with 5 mg nalbuphine hydrochloride
      administered subcutaneously, the response to FAS was again recorded. RESULTS: No
      ominous fetal heart rate (FHR) patterns were observed. FAS reliably increased FHR
      baseline and long-term FHR variability and produced FHR accelerations. Nalbuphine
      hydrochloride analgesia did not produce a significant decrease in long-term FHR
      variability or alter FHR baseline but did reduce the number of FHR accelerations
      recorded. CONCLUSION: FAS-induced FHR accelerations did not differ from those
      observed before analgesia. Analgesia with low doses of nalbuphine did not alter
      fetal response to FAS, which therefore offers a means of assessing fetal well
      being even in the narcotized fetus.

PMID- 8551473
TI  - Conservative management of ovarian hyperstimulation syndrome.
AB  - OBJECTIVE: To evaluate the performance of a conservative treatment protocol for
      ovarian hyperstimulation syndrome (OHSS) that utilized low-dose dopamine, volume
      expanders and diuretics. STUDY DESIGN: Prospective, open trial. RESULTS: Thirteen
      patients met the criteria for diagnosis of severe OHSS during the study period.
      Two of these were in vitro fertilization (IVF) patients who did not undergo
      transfer and so were excluded from analysis. Of the remaining 11, 10 (91%) were
      pregnant. The average time for resolution of the OHSS and discharge from the
      hospital was 6 days (range, 2-11). Compared to levels at admission, there was no
      significant difference in those of sodium, potassium or creatinine after
      resolution of the syndrome. Hemoglobin and hematocrit, however, were
      significantly reduced (P < .03). There were no cases of adult respiratory
      distress syndrome or thrombosis. No pregnancies were interrupted. CONCLUSION:
      Conservative treatment of OHSS is an acceptable form of management. Risky and
      invasive therapies, such as paracentesis, are not warranted.

PMID- 8551474
TI  - Leuprolide acetate for inducing ovulation in women undergoing ovarian
      stimulation.
AB  - OBJECTIVE: To determine whether leuprolide acetate (LA), given subcutaneously at
      the time of follicular maturity in stimulated cycles, can result in ovulation and
      in vivo fertilization. STUDY DESIGN: Sixty-seven women underwent 91 cycles of
      ovarian stimulation (OS) and received a single subcutaneous injection of 1 mg of
      LA when follicular maturity was reached. Only clomiphene citrate (CC) was used
      for 15 cycles, CC/FSH for 66 cycles and human menopausal gonadotropin only for 10
      cycles. Thirty-four cycles were in oligoovulatory women. Eighty-two cycles were
      combined with intra-uterine insemination. RESULTS: Viable pregnancies occurred in
      21/91 cycles (23%). Forty-two women testing with home urinary luteinizing hormone
      (LH) kits noted a surge. Seventy-one or 71 cycles demonstrated a biphasic curve.
      Sixty-eight of 75 cycles demonstrated follicular collapse (91%). Six women had
      serum LH levels of 12 +/- 4, 136 +/- 22 and 17 +/- 3 mIU/mL before and 12 and 36
      hours after LA, respectively. CONCLUSION: LA successfully induced ovulation,
      fertilization and luteinization in women receiving OS. The pituitary LH response
      to LA appeared to be normal in women having OS. The pregnancy rate was similar to
      that generally observed with human chorionic gonadotropin (hCG). A large,
      prospective, randomized study may be warranted to compare LA to hCG since the
      subcutaneous route of LA administration and potential for reduced
      hyperstimulation could be significant advantages, making OS more practical and
      safe.

PMID- 8551475
TI  - Comparing fetal pulse oximetry with scalp pH.
AB  - OBJECTIVE: To determine whether pulse oximetry has the potential to replace scalp
      blood pH sampling in infants with abnormal cardiotocographs. STUDY DESIGN: The
      average scalp oximetry reading in labor recorded with an experimental N400 system
      was compared with fetal scalp blood pH. RESULTS: The average oximetry readings
      were unrelated to the pH of aerobically sampled fetal scalp blood. There was no
      subgroup of acidemic infants with a low oximetry reading. CONCLUSION: Pulse
      oximetry readings with present technology do not reflect scalp pH. The equipment
      is improving, but at this time pulse oximetry is not a simple alternative for
      scalp capillary blood sampling.

PMID- 8551476
TI  - Amnioinfusion for preventing puerperal infection. A prospective study.
AB  - OBJECTIVE: To evaluate the hypothesis that irrigation of the uterine cavity by
      amnioinfusion in women with membranes ruptured for greater than six hours would
      decrease maternal puerperal infection. STUDY DESIGN: We designed a prospective
      study at three teaching institutions. Sixty-eight women were randomized to
      receive either amnioinfusion or routine care. Amnioinfusion was through
      preexisting internal uterine pressure catheters with a 300-500-mL bolus and a 125
      150 mL/h constant drip. Chorioamnionitis and endometritis were evaluated as the
      outcome variables. RESULTS: Women from the amnioinfusion group, n = 36, and the
      control group, n = 32, had similar times in labor (mean 4 hours), times of
      ruptured membranes (mean 18 hours), vaginal examinations (mean 7), gestational
      age (mean 40 weeks), types of anesthesia and methods of delivery. Women who
      received amnioinfusion had significantly less puerperal infection, 9/36, as
      compared to women in the control group, 16/32 (P < .033, relative risk = .5,
      confidence interval .26-.94). There were no cases of neonatal sepsis in either
      group, and there were no complications from the amnioinfusions. CONCLUSION: In
      this study of women at high risk for puerperal infection, amnioinfusion was an
      inexpensive and safe technique for reducing the incidence of infection.

PMID- 8551477
TI  - Romano-Ward syndrome diagnosed as moderate fetal bradycardia. A case report.
AB  - BACKGROUND: Romano-Ward syndrome is a rare, autosomal-dominant cardiac conduction
      defect associated with syncope and life-threatening ventricular arrhythmia in
      children and adults. CASE: A fetus was noted to have moderate fetal bradycardia
      in the antenatal period. When studied postnatally, the child was found to have
      Romano-Ward syndrome. CONCLUSION: This is the first reported case of Romano-Ward
      syndrome diagnosed prenatally as fetal bradycardia. This report confirms that
      moderate fetal bradycardia does not indicate fetal distress, but it does indicate
      that fetuses should be studied for cardiac conduction defects in the neonatal
      period.

PMID- 8551478
TI  - A simple technique for anticipating and managing secondary puncture site
      hemorrhage during laparoscopic surgery. A report of two cases.
AB  - BACKGROUND: Clinically significant hemorrhage from secondary port sites at
      laparoscopy is an uncommon but serious complication and can go unrecognized
      intraoperatively. CASES: A 28-year-old woman undergoing operative laparoscopy
      sustained abdominal wall vessel injury and required a blood transfusion. A second
      patient received the same injury but, when the author's technique was used, had
      minimal blood loss and a benign postoperative course. With this technique, a
      blunt instrument is placed through the sheath and into the peritoneal cavity
      before any secondary port is removed. The sheath is withdrawn, only the probe is
      kept in the abdomen, and then hemorrhage usually becomes evident. CONCLUSION: A
      new technique aids the diagnosis of occult abdominal vessel injury and allows
      rapid recanalization of the secondary trocar sheath paths.

PMID- 8551479
TI  - Placental abruption in association with advanced abdominal pregnancy. A case
      report.
AB  - BACKGROUND: Recognition of advanced abdominal pregnancy and care of the patient
      afflicted with it may present formidable challenges. Aside from the difficulty of
      diagnosing the problem and thereby delaying necessary intervention, management
      can be difficult at best, even when the condition is relatively uncomplicated.
      When it is compounded by a life-threatening complication, such as uncontrollable
      hemorrhage, it challenges the skills of the most experienced obstetrician and the
      resources of the best-equipped facility and its personnel. CASE: Partial
      placental separation was encountered at surgery; it progressed intraoperatively
      despite the care taken to avoid disturbing the placental implantation site.
      Severe hemorrhage was controlled by a combination of aortic compression, packing
      and use of large "liver" sutures incorporating the uterine wall for tamponade of
      the principal placental implantation site, on the mesentery. CONCLUSION: It is
      important to be prepared to deal with the complication of intense intraabdominal
      bleeding in the course of intraoperative management of abdominal pregnancy.

PMID- 8551480
TI  - Postoperative rupture of a hepatic artery aneurysm. A case report.
AB  - BACKGROUND: Hepatic artery aneurysm is a rare finding, and its unsuspected
      rupture in the postoperative period can present a confusing clinical picture.
      CASE: A patient underwent vaginal surgery for complete procidentia and on
      postoperative day 1 developed hemorrhagic shock. Emergency exploratory laparotomy
      revealed a ruptured left hepatic artery aneurysm. CONCLUSION: Hepatic artery
      aneurysms are rare, and when they rupture, prompt diagnosis and therapy are
      essential to survival.

PMID- 8551481
TI  - Vincristine for refractory autoimmune thrombocytopenic purpura in pregnancy. A
      case report.
AB  - BACKGROUND: Autoimmune thrombocytopenic purpura is a common disease during
      pregnancy. Newborns of affected mothers commonly develop thrombocytopenia.
      Standard therapy consists of corticosteroids, hyperimmune gamma globulin and
      splenectomy. CASE: Severe autoimmune thrombocytopenic purpura was diagnosed in a
      22-year-old woman, gravida 2, para 1, at 28 weeks' gestation. A sufficient
      response was obtained after vincristine was added to the treatment with
      corticosteroids, hyperimmune gamma globulin and danazole. A male infant weighing
      2,545 g was delivered by cesarean section at 33.5 weeks' gestation. There were no
      maternal or fetal complications except for severe newborn thrombocytopenia, which
      resolved with medical therapy. CONCLUSION: Vincristine has been used in all
      trimesters of pregnancy, with favorable outcomes in most cases. This is the first
      reported case of successful vincristine treatment for autoimmune thrombocytopenic
      purpura in pregnancy. Vincristine, when carefully used, offers an option for
      unusually refractory cases of autoimmune thrombocytopenic purpura before
      delivery.

PMID- 8551482
TI  - Conserving fertility with early management of cervical pregnancy. A case report.
AB  - BACKGROUND: Cervical pregnancy can be a life-threatening entity, with the
      diagnosis often made on the hysterectomy specimen. A case of distal ectopic
      pregnancy involved the endocervical canal, and prompt diagnosis and treatment
      allowed the preservation of fertility. CASE: The patient presented at six weeks'
      gestation with vaginal bleeding. Serial ultrasound examinations revealed a viable
      pregnancy and ultimately suggested placental implantation within the endocervical
      canal. Curettage was performed using cervical stay sutures at the three and nine
      o'clock positions, with minimal bleeding and no postoperative morbidity. One year
      after the procedure the patient had a spontaneous delivery of a full-term male
      following an unremarkable prenatal course. CONCLUSION: Improvements in sonography
      and serum testing have allowed earlier diagnosis and hence greater success with
      conservative management of cervical pregnancy.

PMID- 8551483
TI  - Poisoning with anti-hypertensive drugs: angiotensin converting enzyme inhibitors.
AB  - The increase in the popularity of ACE inhibitors in the treatment of hypertension
      has resulted in increased use and availability of such drugs. For the majority of
      patients the effects from poisoning or overdosage are mild and close observation
      may be all that is required. When symptoms and signs are more profound hospital
      admission is indicated. Severe hypotension may require intravenous fluids and
      inotropic support.

PMID- 8551484
TI  - End-organ damage in essential hypertension in the elderly.
AB  - To elucidate the characteristics of end-organ damage in essential hypertension in
      the elderly, the progression of end-organ damage, with respect to deterioration
      of renal function and changes in the optic fundi, were compared between young and
      elderly essential hypertensive patients with the same left ventricular mass index
      (LVMI). Forty five elderly hypertensive patients (age > or = 65 years) were
      matched with 40 young patients (age < or = 55 years) for sex and LVMI. All
      studies were performed under hospitalisation to uniform the background of diet
      and daily activity. Compared with young hypertensive patients, elderly patients
      were characterised to have advanced end-organ damage. In young patients, the
      levels of progression of end-organ damage were significantly correlated with each
      other, while in elderly patients no relation was observed. In young patients,
      LVMI was significantly correlated with urinary and plasma noradrenaline, PRA and
      24 h blood pressure. In elderly patients, LVMI correlated only with 24 h systolic
      blood pressure.

PMID- 8551485
TI  - Hypertension in the elderly: 24 h ambulatory blood pressure results from a
      placebo-controlled trial.
AB  - Calcium channel blockers are increasingly used to treat hypertension in elderly
      patients. To assess the effects of low-dose, long-acting verapamil on blood
      pressure (BP) and quality of life (QOL) in elderly patients, verapamil 120-240 mg
      of placebo was given once daily for 8 weeks to 76 patients aged > or = 60 years.
      After a 4-week placebo wash-out period, patients with a sitting DBP of 95-110 mm
      Hg and a mean daytime (6 am to 6 pm) ambulatory DBP > or = 90 mm Hg were entered
      into the study. Twenty four-hour BP monitoring as well as QOL self-assessment and
      digit span testing of cognitive function were performed at the end of the placebo
      wash-out and double-blind treatment periods. Patients treated with verapamil
      showed a significant decrease in mean whole-day BP, while those treated with
      placebo showed a small increase in BP. Treatment differences between the two
      groups in SBP and DBP were each statistically significant (P < 0.01). Significant
      differences were also seen when the 24 h period was divided into daytime and
      night-time readings. Both QOL and digit span testing scores were unchanged from
      baseline for verapamil-treated patients and were not different from the placebo
      treated group. The results of this study demonstrate consistent and significant
      decreases in BP throughout the 24 h period with no adverse effects on QOL or
      cognitive function this this formulation of verapamil in elderly hypertensive
      patients.

PMID- 8551486
TI  - White coat effect in treated hypertensive patients: sex differences.
AB  - Ambulatory blood pressure recordings were performed in patients receiving anti
      hypertensive therapy to determine the prevalence of a white coat effect and to
      evaluate the importance of the sex of the patients with higher office vs.
      ambulatory blood pressure (BP) readings. A white coat effect (office--ambulatory
      BP > or = 20/10 mm Hg) was present in 106 of 152 treated hypertensive patients
      who had a mean office BP (mm Hg) of 174 +/- 2/94 +/- 1 compared with a mean awake
      ambulatory BP of 137 +/- 2/81 +/- 1 (P < 0.001). A severe white coat effect
      (office--ambulatory BP > or = 40/20 mm Hg) was observed in 49 of 152 patients
      with office BP (183 +/- 3/96 +/- 2) being higher (P < 0.001) than mean awake
      ambulatory BP (134 +/- 2/77 +/- 1). A white coat effect was present in 70 of 87
      women but only in 36 of 65 men (P < 0.001). Similarly, a severe white coat effect
      was seen in 41 of 87 women but only in 8 of 65 men (P < 0.001). Female sex and
      office SBP were significantly (P < 0.001) correlated with the presence of a white
      coat or severe white coat effect. Thus, female patients with treated hypertension
      are more likely than men to have a white coat component to their high office BP
      readings. These sex differences in white coat effect should be considered in
      future studies involving patients with hypertension based on high office
      readings.

PMID- 8551487
TI  - Time course of regression of vascular structural changes and its relation to
      cytosolic free calcium in hypertensives after nilvadipine treatment.
AB  - The objective of this study was to assess the regression of vascular structural
      changes seen in essential hypertension after long-term monotherapy with a calcium
      antagonist and to clarify the relations to cytosolic free calcium and
      neurohumoral factors. Blood pressure, minimal vascular resistance (MVR) by strain
      gauge plethysmography, cytosolic free calcium in platelets ([Ca2+]i) by Quin 2
      method, plasma renin activity (PRA) and plasma aldosterone concentration (PAC),
      plasma noradrenaline (PNA) and parathyroid hormone (PTH) were measured in 14
      essential hypertensives during a placebo period and 2 and 6 months after anti
      hypertensive treatment with nilvadipine. Blood pressure decreased from 174 +/-
      10/104 +/- 8 mm Hg during the placebo period to 154 +/- 13/93 +/- 14 mm Hg 2
      weeks after nilvadipine, and the hypotensive effects were found throughout the 6
      month period. Although increased MVR seen in hypertensives did not change after 2
      months (from 2.1 +/- 0.7 to 1.9 +/- 0.6 mm Hg/ml/min per 100 ml tissue (PRU),
      NS), MVR decreased significantly at 6 months (1.6 +/- 0.4, PRU, P < 0.05).
      Elevated [Ca2+]i seen in hypertensives during the placebo period decreased
      significantly 2 months after nilvadipine treatment (156 +/- 26 and 140 +/- 27 nM,
      P < 0.01). The changes in MVR were associated with those in [Ca2+]i 6 months
      after nilvadipine (r = 0.56, P < 0.05). However, the changes in MVR did not
      correlate with those in PRA, PAC, PNA or PTH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8551488
TI  - 'Captopril test', with blood pressure and peripheral renin as response variables
      in hypertensive patients with suspected renal artery stenosis.
AB  - In forty six hypertensive patients in whom a high level of clinical suspicion for
      renovascular hypertension was present on the basis of clinical clues, a captopril
      test was performed with either 25 mg of captopril or placebo on 2 separate days
      to determine prospectively the value of the captopril test. Blood pressure (BP)
      and peripheral renin were used as response variables. All patients had
      discontinued their anti-hypertensive medication and were not salt depleted. In
      all patients selective renal angiography was performed irrespective of the
      results of the captopril test. Twenty patients proved to have uni- or bilateral
      renal artery stenosis (RAS) giving a prevalence of 43%. After the placebo and
      after captopril there were no significant changes (absolute or proportional) in
      BP values between patients with essential hypertension or RAS, either for all
      measurements or if only the fall in BP was taken into account. The receiver
      operator characteristic curves of both baseline and post-captopril peripheral
      renin levels indicate that the captopril test does not discriminate appropriately
      between patients with essential hypertension and RAS. Therefore, we would not
      advise the use of the captopril test as a screening test for RAS in hypertensive
      patients in whom a high level of clinical suspicion for RAS is already present.

PMID- 8551489
TI  - Basal and stimulated platelet calcium and sodium in hypertensive versus
      normotensive black people.
AB  - To examine further the potential role of intracellular cations in hypertension a
      nested case-control study was carried out in conjunction with a population-based
      survey. Based on a house-to-house sampling scheme, 43 hypertensive and 56
      normotensive black residents of Maywood, IL, were recruited. Free cytosolic
      calcium (Cai) and intracellular stores of calcium after stimulation with
      ionomycin were determined in platelets with the fluoroprobe Indo-I; intracellular
      sodium (Nai) measured at rest and after incubation with ouabain was estimated
      with SBFI. Cell sodium content was also assayed in erythrocytes. Resting Cai and
      Nai were not different in hypertensives compared with normotensives, although
      ionomycin-stimulated levels of Cai were correlated with systolic blood pressure
      (r = 0.3; P = 0.04). A consistent set of inter-relations among the various cation
      parameters was observed, lending support to the hypothesis that the cellular
      metabolism of sodium and calcium may be linked in the pathophysiological pathway
      to hypertension.

PMID- 8551490
TI  - In vivo and in vitro studies of the role of HDL in platelet activation in
      normotensive and hypertensive subjects.
AB  - The influence of high density lipoproteins (HDL) on platelet function were
      examined in vivo and in vitro. Intraplatelet, ionised calcium concentrations
      ([Ca2+]i) were measured using the fluorescent dye Quin-2. In vitro, platelet
      responses to AVP were measured in the presence or absence of HDL. Pre-treating
      platelets from normal volunteers with HDL in vitro lowered the [Ca2+]i response
      to AVP but did not significantly affect basal values. In vivo, plasma lipoprotein
      profiles in normotensive (13 men, 17 women) and hypertensive (13 men, 11 women)
      subjects were compared with basal and AVP-stimulated platelet [Ca2+]i values.
      Plasma [HDL] were not related to basal or stimulated [Ca2+]i. Plasma cholesterol
      concentrations were higher in the hypertensive patients largely because low
      density lipoprotein [LDL] were raised in male hypertensive patients. Plasma [LDL]
      and total plasma cholesterol correlated negatively with basal [Ca2+]i (but not
      with AVP-stimulated values) only in this subgroup. In hypertensive patients, AVP
      stimulated [Ca2+]i (but not basal values) were lower than normotensive controls.
      From in vitro studies, it may be concluded that the anti-atherogenic properties
      of HDL might be mediated by inhibition of platelet reactivity. However, ex vivo a
      negative influence of LDL on basal (not stimulated) [Ca2+]i appears to be
      paramount.

PMID- 8551491
TI  - Is insulin resistance a predictor of the blood pressure response to anti
      hypertensive treatment?
AB  - It is a general impression that the blood pressure (BP) response during
      monotherapy in hypertensive subjects is highly variable. As decreased insulin
      sensitivity is a frequent finding in hypertensive patients, the following study
      was performed to evaluate if the degree of insulin sensitivity could predict the
      BP response to different types of anti-hypertensive treatments. Insulin
      sensitivity was evaluated by the hyperinsulinaemic euglycaemic clamp technique
      before initiation of treatment with beta-adrenergic blockers (n = 181), thiazide
      diuretics (n = 60), ACE inhibitors (n = 73), non-dihydropyridine calcium
      antagonists (n = 38), dihydropyridine calcium antagonists (n = 26) or alpha-1
      antagonists (n = 39) over periods of 3-6 months in hypertensive patients. The
      proportion of poor responders, defined as a reduction in the diastolic blood
      pressure (DBP) of < 3 mm Hg ranged between 8% and 30% in the different groups
      despite similar pretreatment DBPs (100-102 mm Hg). A decreased pretreatment
      insulin sensitivity was related to a poor DBP treatment response in the thiazide
      treated group only (r = -0.33, P < 0.05). In this group also obesity, as
      evaluated by body mass index (BMI), was associated with a poor BP response (r =
      0.28, P < 0.05), while obesity was a predictor of a favourable reduction in DBP
      in the group treated with non-dihydropyridine calcium antagonists (r = -0.34, P <
      0.05). These associations were still significant when pretreatment DBP was taken
      into account in multiple regression analysis. Neither age nor sex were found to
      be significant predictors of BP response in any of the treatment groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8551492
TI  - Randomised, double-blind, parallel study of the anti-hypertensive efficacy and
      safety of losartan potassium compared with felodipine ER in elderly patients with
      mild to moderate hypertension.
AB  - This study investigated the anti-hypertensive efficacy and tolerability of once
      daily losartan potassium (50 mg titrated to 100 mg), an angiotensin II receptor
      antagonist, compared with once daily felodipine extended release (ER) (5 mg
      titrated to 10 mg), a calcium channel blocker, after 12 weeks of therapy in
      elderly hypertensive patients. Following a 4-week, single-blind, placebo baseline
      period, qualifying patients were randomly allocated to 12 weeks of double-blind
      treatment with losartan potassium or felodipine ER. After 6 weeks, patients with
      a 24 h post-dose sitting diastolic blood pressure > or = 90 mm Hg had their dose
      doubled for the remaining 6 weeks. At 6 weeks, there was a greater BP response
      for felodipine ER than losartan potassium in elderly patients with mild to
      moderate hypertension. However, after 12 weeks of therapy, losartan potassium
      reduced BP as effectively as felodipine ER with no differences in mean BP
      reduction or anti-hypertensive response category between treatment groups. In
      this study, both treatments were well tolerated; felodipine ER was associated
      with a numerically higher incidence of headache and oedema while the incidence of
      asthenia was numerically higher in losartan-treated patients.

PMID- 8551493
TI  - Effect of long-term celiprolol therapy on haemostasis in essential hypertension.
AB  - Undesirable changes of haemostasis induced by some anti-hypertensive drugs can
      encourage the acceleration of atherogenesis. Therefore, the changes of
      haemostasis parameters in 22 patients with essential hypertension under long-term
      celiprolol therapy (> 2 months) were of interest. In the placebo group of 15
      essentially hypertensive patients there were no significant changes in platelet
      activity. On the other hand, the therapeutic dose of celiprolol was shown to
      reduce total platelet aggregation, without any harmful effects on fibrinolytic
      activity and coagulation inhibitors such as protein C and antithrombin III. The
      metabolic neutrality of celiprolol accompanied by the proven platelet-inhibitory
      tendency is desirable in the new approach to hypertension treatment. Potentially
      anti-thrombotic or at least neutral prothrombotic properties of celiprolol may be
      important in terms of the favourable role of anti-hypertensive drugs in
      cardiovascular morbidity.

PMID- 8551494
TI  - Statement on ambulatory blood pressure monitoring by the German Hypertension
      League. Blood pressure measurement section of the Deutsche Liga zur Bekampfung
      des hohen Blutdruckes e.V. (German Hypertension League).
AB  - Blood pressure (BP) variation is particularly pronounced in those who suffer from
      hypertension. Single measurements should therefore be regarded as no more than
      'snapshots' out of a large number of BP values occurring during the course of a
      day. Indirect ambulatory blood pressure monitoring (ABPM), a method which is
      becoming increasingly common, provides the best information on daily BP using
      automatic measuring and recording equipment. This results in improved diagnosis,
      better treatment indications and better evaluation of the outcome of treatment
      and of prognosis. Compared with ABPM occasional BP measurement by the GP
      overestimates the diagnosis of hypertension and underestimates the
      antihypertensive effect of drugs. ABPM allows the following to be picked up:
      average BP level; circadian BP rhythm; increases in BP which occur only at the
      doctor's office (white coat hypertension); absence of, or reduced, fall in BP
      during sleep; unusual rises or falls in BP; side-effects of anti-hypertensive
      treatment thought to be dependent on the BP level. ABPM is especially suitable
      for evaluating the success of treatment and provides real information on the
      effectiveness of medication. ABPM has a closer correlation with left ventricular
      hypertrophy and with other cardiovascular complications than do BP measurements
      by the GP. There is now a sufficient body of evidence available to support the
      observation that there is a higher rate of organ damage in cases where no night
      time fall in BP occurs than might be expected from the average daily values. The
      acceptance of ABPM can now be termed good to very good.

PMID- 8551495
TI  - Accuracy of an oscillometric automatic blood pressure device: the Omron HEM403C.

PMID- 8551496
TI  - Accuracy of an automatic blood pressure device: the Omron HEM403C.

PMID- 8551497
TI  - Physiological age of ixodid ticks: aspects of its determination and application.
AB  - This review analyzes 30 yr of data concerning physiological age of ixodid ticks.
      The level and state of nutritional reserves in unfed ticks has been proposed as
      an index of tick physiological age. The dynamics of the use of these substances
      reflect tick aging. Thus, physiological age of ixodid ticks is determined by
      estimating the irreversible changes caused by natural vital activity in the body
      of unfed ticks, which inevitably raises the probability of tick death. The 4 age
      groups used in most studies correspond to different periods in the life of unfed
      ticks: the postmolting development, the commencement of active life (= questing
      activity), the midperiod of active life, and the final period of active life. The
      aging of adult ixodid ticks has been studied in natural populations and
      laboratory colonies of different species belonging to several genera. The
      dynamics of age composition through the activity season observed in adult Ixodes
      persulcatus, I. ricinus, and Dermacentor reticulatus from field populations
      correlated well with the known data on the life history of these species.
      Physiological age was successfully used as an indicator of the patterns of tick
      activization (= beginning of questing activity). Tick susceptibility to
      acaricides was shown to increase with tick aging. The success of maintenance,
      reproduction, and transmission of pathogens was found to be strongly influenced
      by tick physiological age. The physiological age can provide information about
      the present physiological status of an individual tick or a group of ticks and,
      on this basis, predictions can be made (for example, life expectancy, degree of
      response to certain factors). The physiological age does not give reliable
      information about the past life of ticks, in particular their calendar age. In
      this respect, the meaning of the physiological age of ixodid ticks corresponds to
      the biological (physiological, functional) age of animals, as used in
      gerontology, and differs from the physiological age of mosquitoes and other
      bloodsucking dipterans. Balashov's histological method of tick age determination
      successfully used by many authors, remains the most appropriate, until now.
      However, there is ample room for further advancement of methodologies of tick age
      assessment. The future methods should be based on the quantitative estimation of
      a number of characters (test-battery) related to different organs or systems.

PMID- 8551498
TI  - General framework for comparative quantitative studies on transmission of tick
      borne diseases using Lyme borreliosis in Europe as an example.
AB  - Models of tick-borne diseases must take account of the particular biological
      features of ticks that contrast with those of insect vectors. A general framework
      is proposed that identifies the parameters of the transmission dynamics of tick
      borne diseases to allow a quantitative assessment of the relative contributions
      of different host species and alternative transmission routes to the basic
      reproductive number, Ro, of such diseases. Taking the particular case of the
      transmission of the Lyme borreliosis spirochaete, Borrelia burgdorferi, by Ixodes
      ticks in Europe, and using the best, albeit still inadequate, estimates of the
      parameter values and a set of empirical data from Thetford Forest, England, we
      show that squirrels and the transovarial transmission route make quantitatively
      very significant contributions to Ro. This approach highlights the urgent need
      for more robust estimates of certain crucial parameter values, particularly the
      coefficients of transmission between ticks and vertebrates, before we can
      progress to full models that incorporate seasonality and heterogeneity among host
      populations for the natural dynamics of transmission of borreliosis and other
      tick-borne diseases.

PMID- 8551499
TI  - Characterization of the Culex pipiens complex (Diptera: Culicidae) in Madagascar.
AB  - Morphological analysis of phallosome and multilocus electrophoresis were used to
      characterize populations of the Culex pipiens L. complex from Madagascar. Samples
      phenotypically and genetically corresponding to Cx. p. quinquefasciatus Say were
      found on the east and west coasts, whereas, on the high plateau, 1 sample was
      composed mostly of phenotypical Cx. p. pipiens L., genetically introgressed with
      quinquefasciatus at some loci (Hbdh, Aat-2, and Hk-1). A hybrid zone between the
      2 taxa was detected on the plateau on a genetic basis, whereas at the
      morphological level a predominance of Cx. p. quinquefasciatus specimens and
      deficit of intermediates was observed. Accordingly, morphological analysis failed
      to describe satisfactorily the hybridization phenomena. Despite the high level of
      gene exchange, a complete mixing of the 2 gene pools apparently does not occur,
      possibly because of differential selective pressures in the climatically
      heterogeneous environment of the Madagascar plateau.

PMID- 8551500
TI  - Prevalence of rickettsia-like organisms and spotted fever group rickettsiae in
      ticks (Acari: Ixodidae) from Zimbabwe.
AB  - The prevalence of rickettsia-like organisms in ticks from Zimbabwe was determined
      using the hemolymph test. Amblyomma hebraeum had the highest prevalence of
      rickettsia-like organisms. Other species with rickettsia-like organisms included
      Amblyomma sparsum, Amblyomma variegatum, Hyalomma marginatum rufipes,
      Ripicephalus simus, Haemaphysalis leachi, Amblyomma rhinocerotis, and Hyalomma
      truncatum. Ticks with no demonstrable rickettsia-like organisms infection were
      Boophilus decoloratus, Haemaphysalis spinulosa, Rhipicephalus appendiculatus,
      Rhipicephalus evertsi evertsi, and Rhipicephalus sanguineus. Polymerase chain
      reaction followed by restriction fragment-length polymorphism analysis on samples
      of hemolymph-positive ticks showed the agent of African tick-bite fever to be
      present in A. hebraeum, Rickettsia conorii to be present in Rhipicephalus simus
      and Haemaphysalis leachi, and a spotted fever group rickettsia similar to that in
      Hyalomma marginatum marginatum ticks from Morocco and Portugal to be present in
      Hyalomma marginatum rufipes.

PMID- 8551501
TI  - Establishment and characterization of three cell lines from Aedes triseriatus
      (Diptera: Culicidae).
AB  - Three cell lines (A.t. GRIP-1, 2, and 3) were established from Aedes triseriatus
      (Say) embryonated eggs or neonate larvae and their morphology, growth, karyotype,
      and isozyme pattern were studied. The isozyme alleles observed in the 3 cell
      lines also were found in adults of the original mosquito colony. Each cell line
      differed in enzymatic, morphological, and karyotypical patterns. La Crosse
      encephalitis (LAC) and snowshoe hare (SSH) viruses, members of the California
      encephalitis virus group, were able to replicate in these 3 cell lines.
      Furthermore, these cell lines, especially A.t. GRIP-1, were more sensitive than
      the Aedes aegypti (L.) (ATC 10) cell line for detection of small amounts of delta
      endotoxin of Bacillus thuringiensis serovar. israelensis (de Barjac).

PMID- 8551502
TI  - Effects of constant temperatures on oviposition and immature development of
      Simulium bidentatum (Diptera: Simuliidae), a vector of bovine Onchocerca
      (Nematoda: Onchocercidae) in central Kyushu, Japan.
AB  - Laboratory developmental studies were carried out on Simulium bidentatum
      (Shiraki) under constant air and water temperatures (7, 10, 13, 16, 19, 22, 25,
      and 28 degrees C). The median time required for female flies to complete oocyte
      maturation after blood feeding decreased from 8 to 1.5 d and the median time from
      blood feeding to oviposition decreased from 16 to 3 d as air temperature
      increased from 7 to 28 degrees C. Air temperatures from 16 to 22 degrees C were
      most suitable for oviposition. An average of 61.4% of eggs hatched. Egg
      developmental period decreased from 17 to 4.5 d when water temperature increased
      from 7 to 19 degrees C and decreased to 3.5 d when water temperature was between
      22 and 28 degrees C. Larval and pupal development occurred at water temperatures
      > or = 13 degrees C, but was most successful from 16 to 22 degrees C. Seven (in
      16 lots) or 6 instars (in 1 lot) were indicated by using the Dyar rule. We
      conclude that S. bidentatum is adapted to moderate weather conditions in spring
      and autumn and that approximately 7 generations of this species occur per year in
      Oita, Japan.

PMID- 8551503
TI  - Infestation of rodents with larval Ixodes ricinus (Acari: Ixodidae) is an
      important factor in the transmission cycle of Borrelia burgdorferi s.l. in German
      woodlands.
AB  - The ecology of Borrelia burgdorferi Johnson et al. s.l. was investigated from
      1987 to 1993 in a preserved woodland in western Germany near Bonn. In selected
      biotopes, host-seeking Ixodes ricinus L. were regularly collected by blanket
      dragging in 1987, 1988, and 1989 and screened for infection with B. burgdorferi.
      Rodents were trapped monthly between April and October in 1988, 1990, 1991, and
      in the winter of 1992-1993, examined for antibodies to B. burgdorferi s.l., and
      inspected for feeding ticks. Ticks collected from rodents were screened for
      spirochete infection. High numbers of host-seeking nymphs were consistently
      collected within a biotope characterized by humid and acid soils. The mean number
      of ticks was significantly lower in biotopes with permeable soils. All small
      mammals captured belonged to the species Apodemus flavicollis Melchior, A.
      sylvaticus L., and Clethrionomys glareolus Schreber. Of 11,680 ticks obtained
      from rodents, 11,674 were I. ricinus, with 97.9% of the ticks being larvae, 2.0%
      nymphs, and 0.1% females. Mean numbers of feeding ticks ranged from 3.4 to 117
      larvae per rodent and from 0.0 to 0.64 nymph per rodent, respectively. High
      levels of larval infestation on rodents were recorded in the same biotope where
      high numbers of host-seeking nymphs were present. Members of the genus Apodemus
      were more heavily infested with I. ricinus larvae than C. glareolus. The mean
      infection prevalence in host-seeking ticks was found to be 1% for larvae, 5% for
      nymphs, and 10-20% for adults. The infection prevalence in host-seeking nymphs
      ranged from 1.1 to 15.4% according to the particular biotope. The values for
      specific infectivity for the Apodemus populations were positively correlated with
      the mean larval infestation, but not with nymphal infestation. The respective
      estimates for C. glareolus were much higher than those for Apodemus spp. in
      biotopes with low tick densities. However, specific infectivity of C. glareolus
      was substantially reduced at sites with high tick abundances. In biotopes with
      high numbers of infected I. ricinus, significantly more rodents were found to
      have antibodies to B. burgdorferi than in biotopes with low abundances of ticks.
      The data show that C. glareolus plays a different role as reservoir host species
      compared with the 2 Apodemus species. This and previous studies suggest that the
      degree of infestation with larval I. ricinus differentially modulates infectivity
      of host species for ticks. We conclude that immune processes in natural reservoir
      hosts induced by B. burgdorferi or I. ricinus bites (or both) are important
      regulatory factors in the transmission cycle(s) of B. burgdorferi.

PMID- 8551504
TI  - Laboratory transmission of Sindbis virus by Aedes albopictus, Ae. aegypti, and
      Culex pipiens (Diptera: Culicidae).
AB  - The susceptibility of Aedes albopictus (Skuse) for Sindbis (SIN) virus was
      examined in the laboratory. Ae. albopictus, Ae. aegypti (L.), and Culex pipiens
      (L.) became infected with and subsequently transmitted SIN virus by bite to
      chicks after feeding on viremic 1-d-old chicks. After ingesting 10(5.3) plaque
      forming units (PFU)/ml, Ae. albopictus had the highest transmission rate (30%) of
      the 3 species. Transmission by Ae. aegypti was less efficient (7%), whereas none
      of the Cx. pipiens transmitted virus. Transmission rates were higher for Ae.
      albopictus (53%) and Cx. pipiens (37%) when they fed on chicks with a viremia of
      10(8.4) PFU/ml. Ae. aegypti was not tested at this dose. Based on these studies,
      the increased geographic distribution of Ae. albopictus, and its opportunistic
      feeding behavior, this species should be considered as a potential bridge vector
      of SIN virus.

PMID- 8551505
TI  - Species composition of sand flies and population dynamics of Phlebotomus papatasi
      (Diptera: Psychodidae) in the southern Jordan Valley, an endemic focus of
      cutaneous leishmaniasis.
AB  - The species composition of sand flies and the seasonality of Phlebotomus papatasi
      Scopoli were studied in the southern Jordan Valley from May to November 1992
      using CDC light traps. Eleven species of sand flies were recorded, including P.
      kazeruni Theodor & Mesghali and P. tobbi Adler & Theodor, which are new records
      for the study area, and Sergentomyia squamipleuris Newstead, which is reported
      for the first time from Jordan. P. papatasi was the most abundant Phlebotomus
      species collected from domestic habitats as well as Psammomys obesus Cretzschmar
      burrows, comprising 89.4 and 99.5% of the total Phlebotomus catches,
      respectively. The catch of P. papatasi in CDC light traps was compared among
      domestic habitats, P. obesus burrows in an agriculturally modified semiarid rural
      habitat, and P. obesus burrows in a natural semiarid rural habitat. Peak P.
      papatasi abundance occurred in September and October and then declined sharply by
      late November. The abundance and temporal association of P. papatasi activity
      with the prevalence of cutaneous leishmaniasis in the study area pointed to the
      significance of this sand fly in the transmission of the parasite.

PMID- 8551506
TI  - Multivariate morphometric discrimination of nymphal and adult forms of the
      blacklegged tick (Acari: Ixodidae), a principal vector of the agent of Lyme
      disease in eastern North America.
AB  - A morphological study of postlarval stages of the blacklegged tick, Ixodes
      scapularis Say, was conducted to examine congruence between northern (formerly I.
      dammini Spielman, Clifford, Piesman & Corwin) and southern morphotypes. The
      character set totaled 17 for females, 25 for males, and 28 for nymphs.
      Populations from 6 geographic areas, F1 progeny from reciprocal crosses between
      I. scapularis from Massachusetts and Georgia, and I. pacificus Cooley & Kohls
      from California were measured. Characters, except cornua length in nymphs, were
      positively correlated with PC1, indicating it was a general-size eigenvector.
      Characters used previously by others to distinguish northern and southern forms
      had a highly positive allometric relationship to general size. In canonical
      variate analysis (CVA) of nymphs, canonical score 1 (CAN1) discriminated I.
      pacificus from all other groups, canonical score 2 (CAN2) discriminated the
      remaining groups in a pattern that correlated with latitude, and canonical score
      3 (CAN3) separated the western (Minnesota and Missouri) from the eastern groups.
      Size-free CVA indicated that north-south discrimination was size dependent, but
      that variation between Missouri and all other groups was not size related.
      Mahalanobis distances between groups within stages were significant with the
      exception of the 2 groups of female progeny of reciprocal crosses (Massachusetts
      x Georgia). Analysis of variance and Student-Newman-Keuls tests revealed that
      each geographic population differed from all other groups in at least 1 nymphal
      character. Nymphs from northern areas (Minnesota, Massachusetts, Maryland)
      differed from those from southern areas (Missouri, North Carolina, Georgia) in
      characters associated with the basis capitulum (longer intercornua and
      interauricular distances, basis capituli, and hypostome internal files, larger
      auriculae, but shorter cornua). Western populations (Minnesota, Missouri)
      differed from eastern populations in idiosomal characters (broader scutum, larger
      coxae III and IV). Frequency polygons of characters with the greatest differences
      indicated that data are continuous and geographic variation is overlapping. Thus,
      the data support the previous contention of conspecificity of I. scapularis and
      I. dammini. I. scapularis appears to be a polytypic species with a widespread
      geographic distribution exhibiting north-south and east-west morphological clines
      in eastern North America.

PMID- 8551507
TI  - Seasonal development of Leptotrombidium akamushi (Acari: Trombiculidae) under
      field temperatures.
AB  - Engorged larvae of Leptotrombidium akamushi (Brumpt), a vector of scrub typhus,
      were reared in small plastic containers placed on the ground and fed fresh eggs
      of the collembolan Sinella curviseta Brook. Engorged larvae obtained in October
      developed into deutonymphs through protonymphs approximately 1 mo before winter
      and became dormant in the cold winter season (approximately 3 mo). Most
      deutonymphs developed into tritonymphs in April and adults in May. Females began
      laying eggs in mid-June and the numbers of unfed larvae showed a peak in August.
      The mites reared from July rapidly developed into adults by August, and laid eggs
      in September. Larvae were most abundant in October, and adults became dormant in
      the winter. The same adults laid eggs from early May to late June and, upon
      hatching, the larval population peaked in early July of the 2nd summer. Most
      larvae died before the 2nd winter. Eggs hatched approximately 3 wk after
      oviposition and longevity of unfed larvae was 2 mo. Because of this very short
      incubation period, L. akamushi larvae occur in the summer, whereas L. pallidum
      Nagayo, Miyagawa, Mitamura & Tamiya, and L. scutellare Nagayo, Miyagawa,
      Mitamura, Tamiya & Tenjin occur in the autumn, although 3 species lay eggs from
      May to August.

PMID- 8551508
TI  - Parasitism of Aedes aegypti and Ae. albopictus (Diptera: Culicidae) by
      Ascogregarina spp. (Apicomplexa: Lecudinidae) in Florida.
AB  - Aedes aegypti (L.) and Ae. albopictus (Skuse) from 40 sites in 17 counties of
      Florida were surveyed for gregarine parasites during the spring and autumn of
      1993 and in July 1994. Larvae collected from containers (mainly tires) were
      dissected to determine the number of gregarine trophozoites present.
      Ascogregarina spp. were found at 70% of the sites and occurred as frequently in
      Ae. aegypti populations as in Ae. albopictus. Within sites, parasite
      distributions were highly variable and aggregated in host populations. Parasite
      loads ranged from 1 to 486 trophozoites per host. Mean parasite load was
      significantly higher in Ae. aegypti larvae (52.5 per host) than in Ae. albopictus
      (33.5 per host). Parasite prevalence was significantly higher in Ae. aegypti
      populations that were not sympatric with Ae. albopictus compared with allopatric
      Ae. albopictus or sympatric populations of either species. In sympatric
      populations, Ae. aegypti tended to have equal or higher parasite prevalence than
      the cohabiting Ae. albopictus. Ascogregarina taiwanensis (Lien & Levine)
      prevalence in Ae. albopictus was significantly higher in areas where these hosts
      have been present for at least 3 yr. These data contribute to the hypothesis that
      parasite-mediated competition may be a factor in the apparent displacement of Ae.
      aegypti by Ae. albopictus in Florida.

PMID- 8551509
TI  - Determining the duration of Ixodes scapularis (Acari: Ixodidae) attachment to
      tick-bite victims.
AB  - The duration of tick attachment is one factor associated with risk for human
      infection caused by several tick-borne pathogens. We measured tick engorgement
      indices at known time intervals after tick attachment and used these indices to
      determine the length of time that ticks were attached to tick-bite victims in
      selected Rhode Island and Pennsylvania communities where the agents of Lyme
      disease and human babesiosis occur. The total body length and width as well as
      the length and width of the scutum were measured on nymphal and adult female
      Ixodes scapularis Say removed from laboratory animals at 0, 12, 24, 36, 48, 60,
      and 72 h after their attachment. Three engorgement indices were calculated at
      each time interval. In addition, engorgement indices measurements were recorded
      for 504 ticks submitted to a commercial laboratory for pathogen detection testing
      between 1990 and 1992. No detectable change was observed in the average
      engorgement indices for either nymphal or adult ticks between 0 and 24 h of
      attachment using any of the engorgement indices. After 24 h of tick attachment,
      all engorgement indices continuously increased: average indices for nymphs
      attached 36, 48, and 60 h were significantly different from those attached < or =
      24 h and from each other. Similarly, average engorgement indices for adult ticks
      attached < or = 36 h were significantly different from those attached for 48 h or
      more. More than 60% of tick-bite victims removed adult ticks by 36 h of
      attachment, but only 10% found and removed the smaller nymphal ticks within the
      first 24 h of tick feeding. The duration of tick attachment may serve as a useful
      predictor of risk for acquiring various infections, such as Lyme disease and
      babesiosis, transmitted by I. scapularis. Regression equations developed herein
      correlate tick engorgement indices with duration of feeding. A table containing
      specific engorgement index prediction intervals calculated for both nymphs and
      adults will allow the practitioner or clinical laboratory to use easily measured
      tick engorgement indices to predict transmission risk by determining the duration
      of feeding by individual ticks.

PMID- 8551510
TI  - Application of desiccant and insecticidal soap treatments to control Ixodes
      scapularis (Acari: Ixodidae) nymphs and adults in a hyperendemic woodland site.
AB  - The desiccant Drione (1% pyrethrin) and Safer's insecticidal soap (0.2%
      pyrethrin) formulated with and without isopropyl alcohol (ROH) were field tested
      against nymphal and adult populations of Ixodes scapularis Say in a hyperendemic
      woodlot in Westchester County, New York. Drione, insecticidal soap, and
      insecticidal soap with ROH provided equivalent levels of control for nymphs and
      adults. Compared with untreated plots, nymphal populations were significantly
      reduced 1 (93.3-100%) and 2 (66.4-85.7%) wk following treatment, and adult
      populations were significantly reduced 1 wk (53.5-62.9%) following treatment.
      Factors possibly contributing to the moderate and shorter period of adult control
      are discussed. Drione and insecticidal soap are effective alternatives to
      residual insecticides and could be an important component of an integrated tick
      management program on residential properties in areas where Lyme disease is
      endemic. Both products lack residual activity and would require repeated
      applications to maintain sufficient levels of control throughout the tick season.

PMID- 8551511
TI  - Polymerase chain reaction-based method for the detection of canine heartworm
      (Filarioidea: Onchocercidae) in mosquitoes (Diptera: Culicidae) and vertebrate
      hosts.
AB  - A polymerase chain reaction (PCR)-based test was developed to aid in
      identification of Dirofilaria sp. and for use in surveys for infected vectors of
      Dirofilaria immitis (Leidy). A set of PCR primers was designed based on the DNA
      sequence of a D. immitis surface antigen gene. The predicted product was a 378
      base-pair DNA fragment. The target fragment was amplified from free D. immitis
      larvae (both L3 and microfilariae), individual infected mosquitoes, pools of 30
      mosquitoes (including a single infected mosquito), infected mosquitoes stored
      desiccated at room temperature for 7 mo, and whole blood from a dog infected with
      D. immitis. These primers did not amplify a homologous fragment from a mermithid
      or from 4 other species of filarioid nematodes (including 1 other Dirofilaria
      species). Third-stage larvae from field-collected mosquitoes also were tested.
      Field-collected L3, identified tentatively as D. immitis, were confirmed by PCR.
      There was no amplification using the PCR test for L3 identified tentatively as
      Dirofilaria sp. (possibly D. tenuis Chandler). These data provide a strong
      indication of the specificity of these primers. The potential utility of this
      technique for detecting the presence of D. immitis in field populations of
      mosquitoes is discussed.

PMID- 8551512
TI  - Field evaluation of deet and a piperidine repellent (AI3-37220) against Amblyomma
      americanum (Acari: Ixodidae).
AB  - Repellent efficacy of deet (N,N-diethyl-3-methylbenzamide) and a piperidine, AI3
      37220, was evaluated topically on human volunteers against lone star tick,
      Amblyomma americanum (L.), nymphs and adults in the field. AI3-37220, at 0.5
      mg/cm2, provided > 90% repellency against adult and nymphal ticks over a 6-h test
      period and showed significantly better repellent efficacy than deet. Deet, at the
      same concentration, provided 85% repellency at 0 h and deteriorated to 55%
      repellency at 6 h.

PMID- 8551513
TI  - Ixodes scapularis (Acari: Ixodidae) at the edge of its range in southern
      Wisconsin.
AB  - This study examined the density and distribution of the blacklegged tick, Ixodes
      scapularis Say, at the edge of its range in southern Wisconsin in 1988 and 1989.
      The study area encompassed sites with ticks at densities ranging from the highest
      recorded in the state to no ticks detected, as known from previous surveys of
      white-tailed deer, Odocoileus virginianus Zimmerman, infestation. Ticks were
      collected from trapped mice, Peromyscus spp., and hunter-killed white-tailed
      deer. A sharp west-to-east decline in I. scapularis density was identified based
      on deer infestation rates. At the edge of the ticks range in southern Wisconsin,
      I. scapularis infestation of Peromyscus Gloger was 1-2 orders of magnitude less
      than in the middle of the range. In this study, white-tailed deer were more
      effective than mice for sampling ticks at low density, as is expected given the
      home range of the hosts and the spatial pattern of ticks. This data set is a
      baseline for judging changes in the distribution and density of I. scapularis in
      southern Wisconsin.

PMID- 8551514
TI  - Assessment of plant tissue feeding by sand flies (Diptera: Psychodidae) and
      mosquitoes (Diptera: Culicidae).
AB  - Plant tissue feeding by Culex pipiens molestus (Forskal) was determined by
      identification of plant residues, differentially stained with Calcofluor, in
      dissected mosquito guts. Such residues were found in 42.3% of 286 field-caught
      mosquitoes. A method for determination of plant tissue feeding from specific
      sources is described. Before feeding branches were suffused with Calcofluor stain
      which binds to plant cell walls; stained residues of this tissue in the insect
      gut are indicative of feeding. Laboratory experiments with Phlebotomus papatasi
      (Scopoli) and C. p. molestus verified that feeding on labeled and untreated
      branches was similar. These experiments quantified the frequency of feeding by
      sand flies on 15 plant species and by the mosquitoes on 6 plant species. Labeled
      branches of plants that were fed upon frequently in the laboratory were used as
      baits in field tests. In the laboratory, the percentage of P. papatasi feeding on
      Prosopis farcta (Macbride) was 75.8% and on Ricinus communis (L.) 67.2%, whereas
      29.4 and 17.9% of the sand flies caught in the field near labeled plants were
      marked, respectively. Similarly, 84.8% of the C. p. molestus fed on Ochradenus
      baccatus (Delile) in the laboratory and 11.0% of the mosquitoes caught near
      labeled baits were marked. These experiments show that plant tissue is common in
      the diet of C. p. molestus in the Jordan Valley, and that the plants tested in
      the field are natural sources of this diet for either sand flies or mosquitoes.

PMID- 8551515
TI  - Description of the egg of Aedeomyia squamipennis (Diptera: Culicidae).
AB  - The egg of Aedeomyia squamipennis (Lynch Arribalzaga) is described with the aid
      of scanning electron micrographs. This study allows separation of the eggs of Ad.
      squamipennis from the eggs of other mosquitoes inhabiting similar aquatic
      vegetation.

PMID- 8551516
TI  - Hypopi (Acari: Hypoderatidae) of the wood stork (Aves: Ciconiiformes;
      Ciconiidae).
AB  - A new species is described and additional host records are presented for 2 other
      species of deutonymphs of the family Hypoderatidae from the subcutaneous adipose
      tissues of the wood stork, Mycteria americana L. Phalacrodectes (Phalacrodectes)
      mycteria n. sp. appears to share affinities with species from both pelicaniform
      and ciconiiform hosts, but it most closely resembles P. (P.) punctatissimus
      (Cerny) Pence & Courtney from pelicans in idiosomal chaetotaxy, cuticular
      sclerotization, and posteriorly divergent, widely separated genital openings. The
      new species differs from this and other species of the genus by its small size,
      the degree of separation of the genital openings with papillae, no secondary
      sclerotization in the perigenital area or surrounding the genital openings, and
      the long filiform setae s and w on genu III. There was a mixed infection of
      Neottialges kutzeri Fain and N. mycteriae Pence in all of 7 wood storks examined
      from Florida and Georgia; P. (P.) mycteria was found in 4 of these hosts. This is
      the 7th species described as a deutonymph in the genus Phalacrodectes. The
      apparent close affinity of P. (P.) mycteria with P. (P.) punctatissimus and
      allied species from pelicaniform versus ciconiiform birds appears to be
      inconsistent with the established host-parasite relationships based on classical
      avian taxonomic relationships. However, this apparent affinity may be more
      reflective of the close relationships between the families of pelicans, ibises
      and spoonbills, and storks as recently proposed by DNA-DNA hybridization studies.

PMID- 8551517
TI  - Pathogenicity of Steinernema carpocapsae and S. glaseri (Nematoda:
      Steinernematidae) to Ixodes scapularis (Acari: Ixodidae).
AB  - The entomopathogenic nematodes Steinernema carpocapsae (Weiser) and S. glaseri
      (Steiner) are pathogenic to engorged adult, blacklegged ticks, Ixodes scapularis
      (Say), but not to unfed females, engorged nymphs, or engorged larvae. Nematodes
      apparently enter the tick through the genital pore, thus precluding infection of
      immature ticks. The timing of tick mortality, and overall mortality after 17 d,
      did not differ between infections by S. carpocapsae and S. glaseri. These
      nematodes typically do not complete their life cycles or produce infective
      juveniles in I. scapularis. However, both species successfully produced infective
      juveniles when the tick body was slit before nematode infection. Mortality of
      engorged I. scapularis females infected by S. carpocapsae was greater than
      uninfected controls, but did not vary significantly with nematode concentration
      (50-3,000 infective juveniles per 5-cm-diameter petri dish). The LC50 was 347.8
      infective juveniles per petri dish (5 ticks per dish). Hatched egg masses of
      infected ticks weighed less than those of uninfected controls. Mortality of
      infected ticks was greatest between 20 and 30 degrees C, and was lower at 15
      degrees C.

PMID- 8551518
TI  - Cloning, sequencing, and characterization of a complementary DNA from Haematobia
      irritans irritans (Diptera: Muscidae) that shares significant homology to a yeast
      ATPase.
AB  - A study of the molecular genetics of the horn fly, Haematobia irritans irritans
      (L.), has resulted in the isolation and sequencing of a 2316-bp complementary DNA
      (cDNA) clone, HFN2b. An open reading frame was found, the deduced 464 amino acid
      sequence of which encodes a protein with 40% identity to AFG1, a member of a
      yeast family of ATPases; it contains an ATP- or GTP-binding P-loop motif.
      Northern and Southern blot analyses do not reveal significant differences in the
      expression of the gene homologous to HFN2b when comparing laboratory-reared horn
      flies that are susceptible or resistant to pyrethroid insecticides.

PMID- 8551519
TI  - Dynamic behaviour of the head-tail junction of myosin.
AB  - It has generally been supposed that flexibility in the head-tail junction of
      myosin is provided by free rotation around the bonds of the polypeptide backbone
      of a few amino acid residues, but direct evidence for this is lacking. Here it is
      shown that the binding of an antibody in this region reveals a novel structure in
      which the bases of the heads are separated by 10 nm, with concomitant 9 nm
      shortening of the tail and movement of the sites of sharp bends in the tail a
      similar distance towards the heads. These results suggest that the junction is a
      dynamic structure in which between 60 and 130 residues of the coiled coil can
      separate to allow the heads to move apart. They suggest a site for the series
      elastic element of the cross-bridge, and have implications for the interactions
      of the two heads with actin subunits in the thin filaments, and the mechanism of
      movement of other two-headed motor proteins, such as kinesins.

PMID- 8551520
TI  - An unusually long-lived antisense RNA in plasmid copy number control: in vivo
      RNAs encoded by the streptococcal plasmid pIP501.
AB  - The main regulator of pIP501 replication is an antisense RNA (RNAIII) that
      induces transcriptional attenuation of the essential RNAII. Previous studies
      identified the termination point in vivo and demonstrated attenuation in vitro.
      This in vivo analysis confirms the appearance of attenuated RNAII dependent on
      RNAIII. Half-lives and intracellular levels of RNAII and RNAIII were determined:
      in a Bacillus subtilis cell harboring a wild-type pIP501 plasmid, approximately
      50 molecules RNAII and 1000 to 2000 molecules of RNAIII were measured,
      respectively. The half-life of RNAII was in the range of that of other target
      RNAs, whereas that of RNAIII (approximately 30 minutes) was unusually long,
      representing a so far unprecedented case of a metabolically stable antisense RNA
      regulating plasmid copy number. Long antisense RNA half-life is predicted to
      yield sluggish control and instability of maintenance. We propose a model for how
      plasmid pIP501 may avoid this problem by using both the repressor CopR and the
      antisense RNAIII for control. Four stem-loop mutants of RNAII/RNAIII with
      elevated copy numbers were characterized for in vitro antisense/target RNA
      binding, RNAIII half-life, incompatibility, and attenuation in vivo. Two classes
      were found: interaction mutants and half-life mutants. The former suggest a key
      function for loop LIII of RNAIII as recognition loop in the primary steps of
      RNAII/RNAIII interaction.

PMID- 8551521
TI  - Three-dimensional structure of glutathione S-transferase from Arabidopsis
      thaliana at 2.2 A resolution: structural characterization of herbicide
      conjugating plant glutathione S-transferases and a novel active site
      architecture.
AB  - Glutathione S-transferases (GST) are a family of multifunctional enzymes involved
      in the metabolization of a broad variety of xenobiotics and reactive endogenous
      compounds. The interest in plant glutathione S-transferases may be attributed to
      their agronomic value, since it has been demonstrated that glutathione
      conjugation for a variety of herbicides is the major resistance and selectivity
      factor in plants. The three-dimensional structure of glutathione S-transferase
      from the plant Arabidopsis thaliana has been solved by multiple isomorphous
      replacement and multiwavelength anomalous dispersion techniques at 3 A resolution
      and refined to a final crystallographic R-factor of 17.5% using data from 8 to
      2.2 A resolution. The enzyme forms a dimer of two identical subunits each
      consisting of 211 residues. Each subunit is characterized by the GST-typical
      modular structure with two spatially distinct domains. Domain I consists of a
      central four-stranded beta-sheet flanked on one side by two alpha-helices and on
      the other side by an irregular segment containing three short 3(10)-helices,
      while domain II is entirely helical. The dimeric molecule is globular with a
      prominent large cavity formed between the two subunits. The active site is
      located in a cleft situated between domains I and II and each subunit binds two
      molecules of a competitive inhibitor S-hexylglutathione. Both hexyl moieties are
      oriented parallel and fill the H-subsite of the enzyme's active site. The
      glutathione peptide of one inhibitor, termed productive binding, occupies the G
      subsite with multiple interactions similar to those observed for other
      glutathione S-transferases, while the glutathione backbone of the second
      inhibitor, termed unproductive binding, exhibits only weak interactions mediated
      by two polar contacts. A most striking difference from the mammalian glutathione
      S-transferases, which share a conserved catalytic tyrosine residue, is the lack
      of this tyrosine in the active site of the plant glutathione S-transferase.

PMID- 8551522
TI  - The crystal structure of ribonuclease Rh from Rhizopus niveus at 2.0 A
      resolution.
AB  - The three-dimensional structure of ribonuclease Rh (RNase Rh), a new class of
      microbial ribonuclease from Rhizopus niveus, has been determined at 2.0 A
      resolution. The overall structure of RNase Rh is completely different from those
      of other previously studied RNases, such as RNase A from bovine pancreas and
      RNase T1 from Aspergillus oryzae. In the structure of RNase Rh, two histidine
      residues (His46 and His109) and one glutamic acid residue (Glu105), which were
      predicted to be critical to the activity from the chemical modification and
      mutagenesis experiments, are found to be located close together, constructing the
      active site. The indole ring of Trp49 plays an important role in preserving the
      active site structure by its stacking interactions with the imidazole ring of His
      109, and by hydrogen bonding with the carboxyl group of Glu105. There exists a
      hydrophobic pocket around the active site, which contains the aromatic side-chain
      of Trp49 and Tyr57. The results of mutagenesis studies suggest that this pocket
      is the base binding site of the substrate.

PMID- 8551523
TI  - Inhibition and catalytic mechanism of HIV-1 aspartic protease.
AB  - The structure of the HIV-1 protease in complex with a pseudo-C2 symmetric
      inhibitor, which contains a central difluoroketone motif, has been determined
      with X-ray diffraction data extending to 1.7 A resolution. The electron density
      map clearly indicates that the inhibitor is bound in a symmetric fashion as the
      hydrated, or gemdiol, form of the difluoroketone. Refinement of the complex
      reveals a unique, and almost symmetric, set of interactions between the geminal
      hydroxyl groups, the geminal fluorine atoms, and the active-site aspartate
      residues. Several hydrogen bonding patterns are consistent with that
      conformation. The lowest energy hydrogen disposition, as determined by
      semiempirical energy calculations, shows only one active site aspartate
      protonated. A comparison between the corresponding dihedral angles of the
      difluorodiol core and those of a hydrated peptide bond analog, calculated ab
      initio, shows that the inhibitor core is a mimic of a hydrated peptide bond in a
      gauche conformation. The feasibility of an anti-gauche transition for a peptide
      bond after hydration is verified by extensive molecular dynamics simulations. The
      simulations suggest that rotation about the C-N scissile bond would readily occur
      after hydration and would be driven by the optimization of the interactions of
      peptide side-chains with the enzyme. These results, together with the
      characterization of a transition state leading to bond breakage via a concerted
      exchange of two protons, suggest a proteolysis mechanism whereby only one active
      site aspartate is initially protonated. The steps of this mechanism are:
      asymmetric binding of the substrate; hydration of the peptidic carbonyl by an
      active site water; proton translocation between the active site aspartate
      residues simultaneously with carbonyl hydration; optimization of the binding of
      the entire substrate facilitated by the flexible structure of the hydrated
      peptide bond, which, in turn, forces the hydrated peptide bond to assume a gauche
      conformation; simultaneous proton exchange whereby one hydroxyl donates a proton
      to the charged aspartate, and, at the same time, the nitrogen lone pair accepts a
      proton from the other aspartate; and, bond breakage and regeneration of the
      initial protonation state of the aspartate residues.

PMID- 8551524
TI  - Evaluation of the severity of Helicobacter pylori infection with urease test: its
      correlation with histopathology and bacterial density.
AB  - In 69 patients, the severity of Helicobactor pylori (H. pylori) infection was
      evaluated by bacterial density of tissue implants and inflammatory responses by
      histology. The specimens were taken from gastric angle and antrum (greater and
      lesser curvature sides) by gastroduodenal endoscopy. In urease test, the severity
      was measured in 3 grades according to color change of the agar: those change are
      within 30 minutes (grade 3), 30 minutes to 3 hours (grade 2), and 3 to 6 hours
      (grade 1), respectively; while the grade 0 indicated no color change occurring 6
      hours after tissue inoculation. The severity of infection was assessed according
      to the bacterial density under high power microscopic fields (Gram's stain).
      Grade 0 indicated no bacterium seen; grade 1, only 1 to 10 bacteria at all
      fields; grade 2, 1 to 3 bacteria in each high power field; and grade 3 was 4
      bacteria or more on average in each high power field. The degree of inflammatory
      response was evaluated by inflammatory cell infiltration (H & E stain) and
      classified into grade 0, 1 and 2, which indicated the inflammatory cell
      infiltration below 50%, between 50% and 75%, and above 75%, respectively. There
      are no positive relationships among urease test reaction time, bacterial density
      grading and degrees of inflammatory cell infiltration. Clinically, the reaction
      time of urease test cannot reflect the severity of H. pylori infection semi
      quantitatively, either in terms of bacterial density or cellular inflammatory
      response.

PMID- 8551525
TI  - Recent experience of penile fracture (1989-1993).
AB  - Penile fracture is an uncommon injury in the genitourinary organ which occurs
      following a blunt injury on the rigid penis. Penile fracture with urethral injury
      is even rarer. A total of 11 new patients with penile fracture were treated at
      our institution from 1989 to 1993. All of these injuries occurred during sexual
      intercourse and received immediate surgical repair to preserve the sexual
      function. Only one patient with complete transection of the urethra received end
      to-end anastomosis of the urethra. Unfortunately, he suffered from urethral
      cutaneous fistula ten days later. Suprapubic urinary diversion was performed in 3
      patients with partial urethral tearing, and they enjoyed satisfactory outcomes
      during the limited follow-up. Immediate surgical repair of tunica albuginea is
      recommended for preserving penile function. If associated with partial urethral
      tear, suprapubic urinary diversion is sufficient to treat urethral lesions.

PMID- 8551526
TI  - Comparison of serum CA15-3 and CEA in breast cancer.
AB  - The monoclonal antibodies CA15-3 were developed against the two antigens 115D8 of
      the human milk fat globule membrane and DF3 of breast cancer. CA15-3 was assayed
      radioimmunologically and CEA was analysed using the enzyme immunoassay. Normal
      control was achieved in 32 healthy women, the mean values for CA15-3 were 11.5 +/
      3.0 u/ml, range from 7.9 to 16.9 u/ml. We compared serum levels of CA15-3 and
      CEA in 121 patients with histologically proved breast carcinoma. CA15-3 levels
      above 25 u/ml and CEA levels above 5 ng/ml were considered positive values. 31 of
      121 patients studied had elevated CA15-3 levels (sensitivity: 25.6%) and 21 of
      121 patients had positive CEA levels (sensitivity 17.4%). 92 of the breast cancer
      patients (76%) did not have metastatic disease. In this group CA15-3 sensitivity
      was 7.6%, while CEA sensitivity was 6.5%. Mean values were 15.1 +/- 6.6 u/ml for
      CA15-3 and 1.78 +/- 2.47 ng/ml for CEA. 29 patients (24%) had metastatic disease.
      In this group, CA15-3 sensitivity was 82.8% and CEA sensitivity was 51.7% (P <
      0.05). Mean values for CA15-3 were 147.5 +/- 175.9 u/ml and 16.9 +/- 24.0 ng/ml
      of CEA. With regard to the correlation of two tumor markers with clinical course
      patients had significantly higher levels of CA15-3 than of CEA in metastatic
      breast cancer. This result suggests CA15-3 to be the more sensitive and more
      specific of the two for metastatic breast cancer detection and monitoring.

PMID- 8551527
TI  - Arthroscopic debridement for osteoarthritis of the knee: a seven years follow-up
      study.
AB  - We reviewed 32 knees with osteoarthritis of the knee treated by either
      arthroscopic debridement in association with drilling the subchondral bone or
      arthroscopic debridement alone and followed for 2.5 to 11 years. Eighteen knees
      had arthroscopic debridement and drilling the subchondral bone, and 14 knees had
      arthroscopic debridement alone. In the group treated with arthroscopic
      debridement and drilling the subchondral bone, 55.6% had good to excellent
      results, 22.2% had fair results, and 22.2% had poor results. In the group that
      had arthroscopic debridement alone, 57.2% had good to excellent results, 35.7%
      had fair results, and 7.1% had poor results. There was better relief of pain in
      the group with arthroscopic debridement alone.

PMID- 8551528
TI  - A clinical analysis of necrotizing fasciitis: a review of 54 cases.
AB  - Necrotizing fasciitis is a severe and sometimes life-threatening soft tissue
      infection that is characterized by rapidly widespreading necrosis of fascia and
      subcutaneous tissue. Fifty-four cases of necrotizing fasciitis were reviewed over
      a 5-year period. Among them, 25 patients (46%) had diabetes mellitus. The
      majority of the wound bacterial cultures (71%) yielded a mixed growing. There
      were negative cultures in six patients, and single organism growth in 14 patients
      (29%). The predominant organisms growth were Streptococci, Staphylococci, and
      Escherichia coli. The overall mortality rate was 22% (12/54). Death was caused by
      systemic septic complications in these patients. All 12 mortalities resulted from
      delayed debridement (averaging 25 days after initial symptoms appeared). Our
      study indicates that the early recognition and prompt debridement of all necrotic
      tissue is essential for reducing the mortality rates of this potentially lethal
      condition.

PMID- 8551529
TI  - A study of different postures on isometric lifting strength in normal college
      students.
AB  - The purpose of this study was to describe norms of isometric lifting strength for
      normal college students and to investigate the effects of gender, body weight,
      height, and upper and lower limb length on lifting strength. Three types of
      lifting (i.e., arm, back, and leg lifting) were measured in a sample of 104
      college students aged between 18 and 26 years. A Force Evaluation and Testing
      System (FET 5000) was used for strength measurements with three standard lifting
      positions. The average of three trials for each lifting strength test was used as
      the subject's test score. The results showed that the highest mean lifting
      strength was recorded for leg lifting in both males and females. Both groups also
      had the lowest score in arm lifting. Of the total sample, there was a difference
      of strength of nearly three- times between leg and arm lifting. Males were
      stronger than females in all lifting patterns. In addition, lifting strengths
      were significantly affected by such variables as sex, weight and height. Body
      weight was an effective predictor of arm lifting strength, and height an
      effective predictor of leg lifting strength. Finally, we found that strength in
      one position had positive relations with strength in other positions. These
      findings and the establishment of data base can in future provide therapists with
      an objective evaluation regarding lifting strength of individuals for clinical
      use.

PMID- 8551530
TI  - [Risk factors related to alcohol use among adolescents of fathers with
      alcoholism].
AB  - The purposes of this study were: 1) to investigate the risk factors related to
      alcohol use among adolescents of fathers with alcoholism. 2) to compare their
      drinking behaviors with the adolescents whose fathers were non-alcoholics. Sixty
      one adolescents, including 29 males and 32 females, aged from 12 to 22 whose
      fathers were alcoholics formed the case group. 122 age and sex matched
      adolescents in a ratio of 1:2 whose fathers were non-alcoholics were recruited as
      the comparison group (normal/control). Data were collected by interview during
      home visits or by mailing questionnaires to patients. The prevalence rates of
      drinking, smoking and betel-nut chewing among the adolescents of fathers with
      alcoholism were 67.2%, 19.7%, 18%. There was no significant difference in
      drinking behavior between the two groups. Beer was the most popular drink in
      adolescents' drinking habits. The most popular motivation of drinking was the
      peer pressure by friends. The significant risk factors of alcohol use among the
      adolescents included male poor mental health status adolescents with behavioral
      problems and alcohol use amongst classmates or friends.

PMID- 8551531
TI  - [Effect of early intervention on the interaction of developmentally delayed
      infants and their mothers].
AB  - The purpose of this study was (1) to examine the interaction patterns of mothers
      and their developmentally delayed infants during free play and instructional
      episodes; (2) to investigate the influence of an early intervention program on
      the interaction patterns of mothers and their developmentally delayed infants;
      and (3) to investigate to what extent the maternal perceptions and expectations,
      perceived stress and involving motivation were associated with maternal behavior
      while interacting with their developmentally delayed infants. The participants of
      this study were twenty-one developmentally delayed infants and their mothers.
      Each mother-child dyad was videotaped in a laboratory playroom for 10-minutes of
      free play and a 5-minute instructional session. Mental and psychomotor
      development of the child were measured by Bayley scale. The perception of child
      development, expectation, and the stress of mothers were measured by a self
      report questionnaire which was designed by a researcher in this study. The
      mothers' motivation of involvement was evaluated by teachers. On year after early
      intervention, it was found that (1) developmentally delayed infants increased
      locomotion, (2) mothers demonstrated more positive emotional expression during
      mother-child interaction, and (3) the score of HOME, mother's involvement, and
      the quality of mother-child interaction which was evaluated by teachers were
      significantly increased. Furthermore, the differences between situations
      indicated that the developmentally delayed infants were more toy-oriented during
      play than instruction. The mothers tended to be more helpful in attitude while
      they instructed their children. The mother's perception of child development and
      stress were found to be the critical factors affecting maternal teaching,
      controlling, and caring behavior.

PMID- 8551532
TI  - Effect of neuromuscular activity on the response to botulinum toxin injections in
      spasmodic dysphonia.
AB  - Spasmodic dysphonia (SD), a neurologic disorder characterized by involuntary
      vocal spasms during speech, has been effectively treated by injections of
      botulinum toxin (BT) into the laryngeal muscles. The aim of the present study was
      to determine if the therapeutic response to BT is enhanced by immediate and
      continuous activation of the injected muscles. Twenty SD patients were randomized
      into two groups following bilateral injections: vocal rest for 30 minutes and
      continuous vocalization for 30 minutes. Evaluations consisted of voice ratings by
      expert observers, acoustic measurements using computer analyses, and laryngeal
      aerodynamic measurements. The findings suggest that vocal rest, rather than
      vocalization, produces a superior and longer lasting response in SD patients
      receiving BT injections. It is recommended that SD patients refrain from post
      injection vocalization to maximize the therapeutic effects of BT.

PMID- 8551533
TI  - Long-term effects of neuromuscular rehabilitation of chronic facial paralysis.
AB  - Although chronic facial dysfunction can be improved with neuromuscular
      biofeedback therapy, it is uncertain whether this improvement is maintained after
      such therapy ends, or whether post-therapy, home exercise programs optimize this
      improvement. We aimed to clarify these issues. Post-therapy facial function, in
      38 previously treated patients, was blindly assessed using the House grading
      system, 1 to 41 months after ending therapy. Results were compared with pre
      therapy function. It was found that post-therapy function was better than pre
      therapy function in most patients (40%), it was worse in some (26%), and was
      unchanged in the rest. This surprising result occurred because, although most
      patients who recently stopped therapy (1 to 6 mo) had improved significantly, the
      longer other patients were out of therapy, the more they had tended to
      deteriorate, particularly those who had been practicing. Results suggested that
      unsupervised, post-therapy, home exercise programs may be detrimental, and that
      new post-therapy programs may be required to maintain the benefits of regular
      therapy.

PMID- 8551534
TI  - Effect of age and training schedules on balance improvement exercises using
      visual biofeedback.
AB  - There has been a growing popularity and success rate of balance rehabilitation
      programs, and this success is paralleled by the growth of technology, making
      available instruments that provide objective, quantitative, and immediate
      results. The Balance Master is such a commercially available instrument,
      consisting of a dual-force platform connected to a micro-computer that provides
      visual feedback of the centre of gravity (COG) in relation to the theoretical
      limits of stability. Spontaneous body sway can be measured in a static central
      position, or in peripheral positions around the limits of stability (peripheral
      sway area). The trajectory between targets can also be analyzed in terms of time
      (transition time) and accuracy (path error) of transition, which gives a
      quantitative measure of dynamic movement of the COG. This study examined the
      practice effect that occurs while using this instrument over repeated sessions
      for two schedules of training (daily and weekly) and over two age groups (20-35
      years, and 60-75 years). Each group completed a series of postural exercises,
      with an assessment of static and dynamic postural variables before and after
      training, and at approximately 3 and 6 weeks post-training. Spontaneous body sway
      was measured with eyes open, eyes closed, and with visual feedback of the COG. No
      significant changes were observed in these variables as measured over the four
      standard assessment occasions. Peripheral sway area and path error decreased
      significantly for both the daily and weekly training groups from pre- to post
      training, and these skills were retained over both retention tests, whereas the
      tendency toward decreasing transition time was not significant.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8551535
TI  - Effect of Lactobacillus acidophilus on antibiotic-associated gastrointestinal
      morbidity: a prospective randomized trial.
AB  - Oral antibiotic therapy can alter the gastrointestinal microflora and result in
      troublesome gastrointestinal complaints. Patients who have experience with broad
      spectrum antibiotics may be reluctant to start or to comply with antibiotic
      therapy due to the associated discomfort. In the field of otolaryngology, oral
      antibiotic therapy is commonplace, and patient intolerance of a particular
      antibiotic may result in compromise to a less effective choice. Yogurt, which
      contains Lactobacillus acidophilus, is often recommended by practitioners to help
      reduce the side effects of oral antibiotic therapy. We wanted to objectively
      evaluate the effect of orally administered L. acidophilus on the gastrointestinal
      side effects of oral broad-spectrum antibiotic therapy. Twenty-seven outpatients,
      10 years of age or older, with ear, sinus, or throat infections, in whom
      amoxicillin/clavulanate was felt to be the antibiotic of choice, were randomly
      assigned to amoxicillin/clavulanate only, or amoxicillin/clavulanate and
      Lactobacillus treatment groups. Each patient was advised by the nursing staff to
      consume a well-balanced diet, and a detailed explanation of the medication
      schedule was given. A questionnaire was given to each patient at the conclusion
      of therapy. The data were analyzed using Spearman's rank-order correlations.
      Concomitant therapy of L. acidophilus with amoxicillin/clavulanate was associated
      with a significant decrease in patient complaints of gastrointestinal side
      effects and yeast superinfection. Almost all patients (89%) reported resolution
      of infection during the course of therapy. We believe that use of L. acidophilus
      is warranted in patients on broad-spectrum antibiotic therapy with
      gastrointestinal complaints.

PMID- 8551536
TI  - Adult-acquired laryngeal stenosis: a study of prognostic factors.
AB  - We reviewed cases of adult-acquired laryngeal stenosis treated at the Health
      Sciences Centre in Winnipeg, Manitoba, over a 15-year period. We studied the
      influence of various factors on the final outcome including age, sex, etiology,
      associated conditions, length and diameter of the stenotic segment, as well as
      its anatomic site. We found a total of 32 patients ranging in age from 16 to 73
      years. Fifty-five percent were caused by intubation and 16% by external trauma.
      Other causes included inflammatory diseases, irradiation, and burns. The
      subglottis was involved in 82% of the total number of cases reviewed. We studied
      the probability of decanulation over time by using the Kaplan-Meier survival
      curves. We then identified the independent factors affecting the probability and
      time of decanulation by using the Cox Proportional Hazards model. External trauma
      was found to have the best outcome when compared to other etiologies. The
      anatomic site of stenosis and its length were independent determinants of
      outcome, while its diameter was not. Involvement of the glottis in subglottic
      stenosis led to a significantly poorer outcome. We recommend the use of the
      length and site of stenosis as primary prognostic factors in the assessment of
      acquired laryngeal stenosis in the adult population.

PMID- 8551537
TI  - Intrathoracic pressure variations in obese habitual snorers.
AB  - Six obese patients with complaints of snoring and daytime fatigue were monitored
      with polysomnography (PSG) and continuous recording of esophageal pressure (Pes)
      during 1 night. Nonapneic episodes in different sleep stages, with and without
      snoring, were selected and analysed. Peak to peak pressure was found to be
      significantly increased during snoring in sleep stages 2 and 3/4 with blood gas
      variations within the limits of normal unobstructed breathing, indicating
      increased respiratory effort. The present investigation supports the assumption
      that daytime tiredness in nonapneic patients can be linked to increased
      respiratory effort during sleep and that continuous esophageal pressure measuring
      may contribute to assessment of this condition.

PMID- 8551538
TI  - Mechanisms of resistance of human tumours to anticancer drugs of the platinum
      family: a review.
AB  - The introduction of cisplatin and its less toxic analog carboplatin into
      anticancer chemotherapy regimens has greatly improved the initial response rate
      of various solid tumours, including squamous cell carcinoma of the head and neck.
      However, relapse of a drug-resistant tumour occurs with a high frequency, and
      remains the greatest impediment to successful chemotherapy treatment. Studies of
      cultured, drug-selected, resistant cell lines from numerous laboratories have
      suggested a variety of potential mechanisms of resistance, the most common of
      which are (1) reduced intracellular accumulation of drug, (2) enhanced removal of
      platinum adducts from DNA, (3) increased cellular glutathione, and (4) increased
      cellular metallothionein. This article describes the contribution of each of
      these mechanisms at a molecular level. By identifying markers or assays for each
      of these phenotypes, the importance of each as a mechanism of resistance in
      patient tumours can be ascertained. Then, methods of circumventing resistance can
      be utilized, with the intent of improving the success of platinum chemotherapy
      against squamous cell carcinoma in the head and neck.

PMID- 8551539
TI  - Simple sublingual ranulas: pathogenesis and management.
AB  - Simple ranulas in the floor of the mouth usually reflect a mucus escape reaction
      that develops after disruption of sublingual gland elements. As such, they
      comprise an accumulation of mucus within connective tissue and lack an epithelial
      lining. Simple ranulas should be distinguished from cervical, or plunging,
      ranulas. Recommended treatments for simple ranulas usually involve excision of
      the ipsilateral sublingual gland, "marsupialization," or simple excision of the
      cyst. Alternatively, the ranula can be treated with the placement of a silk
      suture or seton into the dome of the cyst. Four cases using this technique are
      reported.

PMID- 8551540
TI  - Unilateral supraglottitis in adults: fact or fiction.
AB  - Supraglottitis and epiglottitis have been described for many years by various
      authors. Haemophilus influenzae type b is the primary cause of childhood
      epiglottitis, which classically appears between the ages of 2 and 4 years. Onset
      is usually acute and the presentation can be dramatic with drooling, high
      temperatures, and stridor. Compared to childhood supraglottitis, adult
      supraglottitis usually pursues a more indolent course with no significant airway
      compromise and no identifiable pathogen. Rarely, adult supraglottitis can
      resemble its childhood counterpart with acute respiratory compromise secondary to
      H. influenzae infection. Although most incidences of adult supraglottitis are
      infectious in origin and involve the entire supraglottitis and epiglottis, we
      present two cases of unilateral supraglottitis caused by inhalation of a hot wire
      screen used as a filter for smoking crack cocaine.

PMID- 8551541
TI  - Eosinophilic granuloma presenting as chronic otitis media: pitfalls in the
      diagnosis of aural polyps in children.
AB  - The case of a 7-year-old boy with multifocal eosinophilic granuloma, initially
      presumed to be chronic otitis media, is presented. A review of other similar
      cases in the literature reveals that a delay in diagnosis is not uncommon, and a
      high index of suspicion is necessary to avoid an unfavourable outcome. Early in
      the evaluation of an aural polyp, sufficient biopsies should be performed and
      computerized tomography scanning should be considered.

PMID- 8551542
TI  - Vestibular function pre- and post-cochlear implantation.

PMID- 8551543
TI  - Development of hydrosalpinx during ovulation induction.
AB  - We have observed that hydrosalpinx develops in some patients undergoing ovulation
      induction as part of in vitro fertilization-embryo transfer and gamete
      intrafallopian transfer programs. Increased tubal secretions due to multihormonal
      stimulation causes a blocked tube to distend by the time of oocyte harvest. In a
      subset of women, hydrosalpinx was not identified on initial pelvic sonograms.
      Hydrosalpinx became apparent during serial sonography to monitor follicular
      development. We performed a retrospective chart review of these cases in order to
      confirm this finding with hysterosalpingography or laparoscopy. Nine of 316 women
      developed unilateral (eight cases) or bilateral hydrosalpinx (one case) during
      stimulation. Recognition of this sonographic finding is important to the
      referring physician because it has important therapeutic and outcome
      implications.

PMID- 8551544
TI  - Transvaginal visualization of the cervix after instillation of water in the
      vaginal canal.

PMID- 8551545
TI  - Popliteal vein compression due to popliteal artery aneurysm: effects of aneurysm
      size.
AB  - Unlike the venous compression associated with larger popliteal artery aneurysms,
      which frequently is associated with deep vein thrombosis, the venous compression
      caused by the moderate sized (greater than 2 cm and less than 3 cm) aneurysms in
      the reported cases is not associated with thrombosis. The extrinsic compressive
      effect of these moderate sized popliteal artery aneurysms on the adjacent vein is
      shown to vary with the patient's leg position. Three of the four patients with
      unilateral leg swelling discussed here had bilateral popliteal artery aneurysms.
      In these cases, the contralateral leg had a small popliteal aneurysm (less than 2
      cm) and no leg swelling was present. The cases suggest that popliteal artery
      aneurysm size is an important factor in determining the type of venous
      obstruction that results from the extrinsic compression of the ipsilateral
      popliteal vein. The described phenomenon of a popliteal artery aneurysm having
      the effect of restricting flow in the ipsilateral popliteal vein must be included
      as a differential diagnosis among the causes of unilateral leg swelling in the
      absence of deep vein thrombosis.

PMID- 8551546
TI  - Ease and accuracy of evaluation of fetal hands during obstetrical
      ultrasonography: a prospective study.
AB  - Hand malformations characterize many congenital syndromes, including mendelian
      disorders, skeletal dysplasias, and karyotype abnormalities. Although
      identification of a hand anomaly alters obstetrical management, evaluation of the
      fetal hands is not included in current ultrasonographic guidelines. We
      prospectively studied the utility of allotting up to 5 min to examine fetal hands
      during obstetrical ultrasonography. Both hands were visualized in 87% of patients
      (188 of 215). Eight hand abnormalities were present at delivery. Six had been
      identified antenatally, four during the study with ultrasonography. There were no
      false positives. Four fetuses with hand malformations were aneuploid. Fetal hands
      should be examined during a comprehensive obstetrical sonographic evaluation,
      especially when risk factors for aneuploidy are present.

PMID- 8551547
TI  - Ultrasonographic demonstration of normal axillary lymph nodes: a learning curve.
AB  - High frequency transducers with near field resolution allow visualization of
      superficial structures in the axilla, such as the lymph nodes, which could not be
      visualized with older equipment. We have been able to observe normal axillary
      nodes in 61.5% of 26 women who had histologic correlation of normal lymph nodes
      at axillary dissection. We studied 663 women with a clinically palpable breast
      lump using breast and axillary ultrasonography. They were divided into four
      groups. The first group consisted of all women who had undergone surgery and had
      histologic correlation of axillary nodes. The second, third, and fourth groups
      were made up of three consecutive series of 221 women examined. Women from group
      one were included in groups two, three, and four. A steep learning curve of 7.1
      to 41.9 to 64.7% was observed in the detection of normal axillary nodes,
      suggesting that these appearances can be recognized easily.

PMID- 8551548
TI  - Normal interval fetal growth rates based on obstetrical ultrasonographic
      measurements.
AB  - Analyzing fetal interval growth may improve detection of growth abnormalities.
      This study establishes normal limits for growth rates of fetal biparietal
      diameter, abdominal diameter, abdominal circumference, and femur length. Fetal
      measurements were obtained during 1450 obstetrical sonographic examinations in
      510 patients with normal-weight term deliveries. Using a random-effects model for
      longitudinal data, cubic curves of size versus mean gestational age were fitted
      using a restricted maximum likelihood technique. Quadratic growth rate curves
      were then calculated as derivatives of the fitted curves. The growth rate
      equations are as follows: Biparietal diameter growth rate = 2.59 + 0.127 (MGA) -
      0.000447 (MGA)2; abdominal diameter growth rate = 3.61 + 0.0325 (MGA) - 0.0017
      (MGA)2; abdominal circumference growth rate = 11.3 + 0.102 (MGA) - 0.00534
      (MGA)2; and femur length growth rate = 5.49 - 0.17 (MGA) + 0.00181 (MGA)2. Rates
      are expressed in mm/wk and mean gestational age in wk. Because standard
      deviations depend on the time interval between examinations, separate growth rate
      tables are provided for intervals of 4, 6, 8, and > or = 10 weeks.

PMID- 8551549
TI  - Power Doppler sonography enhances visualization of orbital vessels.
AB  - Our study was intended to determine whether power Doppler sonography can be
      considered superior to color Doppler technique in depiction of normal orbital
      vasculature. Ten healthy volunteers (20 eyes) were examined with a 10 MHz linear
      probe; each orbital vessel was recorded with both color and power Doppler
      methods; the images were reviewed independently by all the observers, who agreed
      that power Doppler clearly is superior to color Doppler technique for evaluation
      of the anatomy of orbital arteries and veins.

PMID- 8551550
TI  - Ovarian dysgerminoma: color Doppler ultrasonographic findings and comparison with
      CT and MR imaging findings.
AB  - We describe three cases of ovarian dysgerminoma in which color Doppler sonography
      demonstrated multilobulated solid ovarian masses with prominent flow signal in
      the fibrovascular septa. This color Doppler sonographic finding of fibrovascular
      septa correlated well with the computed tomographic, magnetic resonance imaging,
      and pathologic findings, and it may suggest the diagnosis of ovarian
      dysgerminoma.

PMID- 8551551
TI  - Prenatal sonographic findings of agenesis of the right and left portal veins and
      associated intrahepatic portosystemic shunts.

PMID- 8551552
TI  - Pseudodissection of the abdominal aorta on color Doppler imaging.

PMID- 8551553
TI  - Transcapsular arterial collateralization of a liver allograft after hepatic
      artery occlusion in an adult: color Doppler ultrasonographic diagnosis.

PMID- 8551554
TI  - Prenatal diagnosis of orofaciodigital syndrome: Mohr type.

PMID- 8551555
TI  - Separate origins of the left internal and external carotid arteries directly from
      the aortic arch: duplex sonographic findings.

PMID- 8551556
TI  - Complete intrauterine resolution of fetal congenital cystic adenomatoid
      malformation of the lung type III.

PMID- 8551557
TI  - Portal venous Doppler findings in a bone marrow transplant patient with cardiac
      tamponade.

PMID- 8551558
TI  - Ras complements the carboxyl terminus of v-Abl protein in lymphoid
      transformation.
AB  - Abelson murine leukemia virus (Ab-MLV) mutants expressing v-Abl proteins lacking
      the carboxyl terminus are compromised in the ability to transform lymphoid but
      not NIH 3T3 cells. This feature correlates with the presence of low levels of
      phosphotyrosine in lymphoid cells infected with carboxyl-terminal truncation
      mutants. In contrast, high levels of phosphotyrosine are observed in NIH 3T3
      cells infected with wild-type and mutant Ab-MLV. Two downstream targets affected
      in lymphoid transformants are the GTPase-activating protein and GTPase-activating
      protein-associated protein p62, molecules which are heavily tyrosine
      phosphorylated in lymphoid cells transformed by wild-type Ab-MLV but not carboxyl
      terminal truncation mutants of Ab-MLV. This difference suggested that signaling
      mediated via the Ras pathway may be compromised in lymphoid cells expressing the
      carboxyl-terminal truncation mutants. Consistent with this idea, expression of v
      Ha-ras complemented these mutants in primary bone marrow transformation assays
      and increased transformation frequencies obtained with the Ab-MLV mutants 8- to
      20-fold. These data suggest that a biologically important link exists between the
      carboxyl terminus of v-Abl protein and the Ras pathway. Signals transmitted via
      this connection may enhance those mediated via other regions of the v-Abl protein
      and facilitate transformation of primary, nonimmortalized cells such as pre-B
      lymphocytes.

PMID- 8551559
TI  - Evidence for a second function of the MA sequence in the Rous sarcoma virus Gag
      protein.
AB  - During retrovirus assembly, Gag proteins bind to the inner leaflet of the plasma
      membrane to initiate the budding process. The molecular basis of this protein
      lipid interaction is poorly understood. For the human, immunodeficiency virus
      type 1 Gag protein, we recently reported that the membrane-binding domain resides
      within the N-terminal 31 amino acids and consists of two components: myristate
      and a cluster of basic residues, which together promote membrane binding in vitro
      and budding in vivo (W. Zhou, L. J. Parent, J. W. Wills, and M. D. Resh, J.
      Virol. 68:2556-2569, 1994). The positively charged residues associate
      electrostatically with acidic phospholipids to stabilize membrane binding, while
      myristate provides membrane-binding energy via hydrophobic interactions. Here we
      demonstrate that the human immunodeficiency virus type 1 Gag membrane-binding
      domain can fully replace the membrane-targeting function of the N-terminal 100
      residues of the non-myristylated Rous sarcoma virus (RSV) Gag protein. To further
      explore the importance of myristate and basic residues in membrane binding, we
      developed a gain-of-function assay whereby budding was restored to defective
      mutants of RSV Gag. Detailed mutational analysis revealed that the position,
      number, and context of charged residues are crucial to budding. Myristate
      provides additional membrane-binding energy, which is critical when a Gag protein
      is near the threshold of stable membrane association. Finally, viruses with
      altered matrix (MA) proteins that are noninfectious, even though they produce
      particles with high efficiency, were identified. Thus, we present the first
      evidence that the RSV MA sequence plays two distinct roles, membrane binding
      during particle assembly and a second, as yet undefined function required for
      viral infectivity.

PMID- 8551560
TI  - Role of the karyopherin pathway in human immunodeficiency virus type 1 nuclear
      import.
AB  - The interaction of the human immunodeficiency virus type 1 (HIV-1) nucleoprotein
      complex with the cell nuclear import machinery is necessary for viral replication
      in macrophages and for the establishment of infection in quiescent T lymphocytes.
      The karyophilic properties of two viral proteins, matrix (MA) and Vpr, are keys
      to this process. Here, we show that an early step of HIV-1 nuclear import is the
      recognition of the MA nuclear localization signal (NLS) by Rch1, a member of the
      karyopherin-alpha family. Furthermore, we demonstrate that an N-terminally
      truncated form of Rch1 which binds MA but fails to localize to the nucleus
      efficiently blocks MA- but not Vpr-mediated HIV-1 nuclear import.
      Correspondingly, NLS peptide inhibits the nuclear migration of MA but not that of
      Vpr and prevents the infection of terminally differentiated macrophages by vpr
      defective virus but not wild-type virus. These results are consistent with a
      model in which Rch1 or another member of the karyopherin-alpha family, through
      the recognition of the MA NLS, participates in docking the HIV-1 nucleoprotein
      complex at the nuclear pore. In addition, our data suggest that Vpr governs HIV-1
      nuclear import through a distinct pathway.

PMID- 8551561
TI  - The human foamy virus pol gene is expressed as a Pro-Pol polyprotein and not as a
      Gag-Pol fusion protein.
AB  - It has been reported recently that the human foamy virus (HFV) Pol polyprotein of
      120 kDa is synthesized in the absence of the active HFV aspartic protease. To
      gain more information on how the 120-kDa Pro-Pol protein is synthesized, mutant
      HFV genomes were constructed and the resulting proviruses were analyzed with
      respect to HFV pol expression and infectivity. HFV proviruses that contain
      termination codons in the nucleocapsid domain of gag and thus lack a gag-pol
      overlap region assumed to be required for translational frameshifting,
      nevertheless expressed the 120-kDa Pro-Pol precursor, the 80-kDa reverse
      transcriptase/RNase H, and a 40-kDa integrase in amounts similar to those
      observed for wild-type genomes. Since a Gag-independent expression of authentic
      Pol proteins was detectable in cells transfected with eukaryotic HFV pol
      expression plasmids, the data indicate that the HFV Pol precursor of 120 kDa is
      expressed independently of Gag by a mechanism that does not rely on ribosomal
      frameshifting, since the postulated HFV Gag-Pol protein of 190 kDa was not
      detectable under the conditions used. Furthermore, replacement of the Met residue
      by Thr at position 9 in pol within the gag-pol overlap region resulted in
      strongly reduced HFV Pol polyprotein expression and infectivity of the resulting
      proviruses. This Met residue of pol conserved in foamy virus sequences is the
      likely candidate for translational initiation of the 120-kDa Pro-Pol polyprotein.
      trans complementation of the HFV mutant with the Met-to-Thr substitution in the
      pol gene by a eukaryotic plasmid that expressed the HFV Pro-Pol protein resulted
      in partial recovery of infectivity. When HFV pol was fused in frame to gag, an
      engineered 190-kDa Gag-Pol fusion protein was formed and the enzymatic activity
      of the HFV protease was partially retained. The results imply that HFV is the
      first retrovirus that expresses a Pol polyprotein without formation of a Gag-Pol
      fusion protein.

PMID- 8551562
TI  - Mutations within the 5' nontranslated RNA of cell culture-adapted hepatitis A
      virus which enhance cap-independent translation in cultured African green monkey
      kidney cells.
AB  - Mutations in the 5' nontranslated RNA (5'NTR) of an attenuated, cell culture
      adapted hepatitis A virus (HAV), HM175/P16, enhance growth in cultured African
      green monkey kidney (BS-C-1) cells but not in fetal rhesus monkey kidney (FRhK-4)
      cells (S. P. Day, P. Murphy, E. A. Brown, and S. M. Lemon, J. Virol. 66: 6533
      6540, 1992). To determine whether these mutations enhance cap-independent
      translation directed by the HAV internal ribosomal entry site (IRES), we compared
      the translational activities of the 5'NTRs of wild-type and HM175/P16 viruses in
      two stably transformed cell lines (BT7-H and FRhK-T7) which constitutively
      express cytoplasmic bacteriophage T7 RNA polymerase and which are derived from BS
      C-1 and FRhK-4 cells, respectively. Translational activity was assessed by
      monitoring expression of a reporter protein, chloramphenicol acetyltransferase
      (CAT), following transfection with plasmid DNAs containing bicistronic T7
      transcriptional units of the form luciferase-5'NTR-CAT. In both cell types,
      transcripts containing the 5'NTR of HM175/P16 expressed CAT at levels that were
      50- to 100-fold lower than transcripts containing the IRES elements of Sabin type
      1 poliovirus or encephalomyocarditis virus, confirming the low activity of the
      HAV IRES. However, in BT7-H cells, transcripts containing the 5'NTR of wild-type
      virus. This translational enhancement was due to additive effects of a UU
      deletion at nucleotides 203 and 204 and a U-to-G substitution at nucleotide 687
      of HM175/P16. These mutations did not enhance translation in FRhK-T7 or Huh-T7
      cells (a T7 polymerase-expressing cell line derived from human hepatoblastoma
      cells) or in vitro in rabbit reticulocyte lysates. These results demonstrate that
      mutations in the 5'NTR of a cell culture-adapted HAV enhance viral replication by
      facilitating cap-independent translation in a cell-type-specific fashion and
      support the concept that picornaviral host range is determined in part by
      differences in cellular translation initiation factors.

PMID- 8551563
TI  - Role of protein kinase A and the serine-rich region of herpes simplex virus type
      1 ICP4 in viral replication.
AB  - Efficient expression of herpes simplex virus genes requires the synthesis of
      functional ICP4, a nuclear phosphoprotein that contains a prominent serine-rich
      region between amino acids 142 and 210. Residues in this region not only are
      potential sites for phosphorylation but also are involved in the functions of
      ICP4. By comparing the growth of a virus in which this region is deleted (d8-10)
      with wild-type virus (KOS) in PC12 cells or PC12 cells that are deficient in
      cyclic AMP-dependent protein kinase (PKA), two observations were made: (i) the
      growth of wild-type virus was impaired by 1 to 2 orders of magnitude in the PKA
      deficient cells, indicating the involvement of PKA in the growth cycle of herpes
      simplex virus type 1, and (ii) while the growth of d8-10 was impaired by almost 2
      orders of magnitude in wild-type cells, it was not further impaired (as was that
      of wild-type virus) in PKA-deficient cells, implicating the region deleted in d8
      10 as a possible target for cellular PKA. In trigeminal'ganglia of mice, the d8
      10 mutant virus grew poorly; however, it established latency in nearly 90% of
      ganglia tested. Studies of the phosphorylation of wild-type and d8-10 ICP4
      proteins revealed that the serine-rich region is a major determinant for
      phosphorylation of ICP4 in vivo and that the phosphorylation state could change
      as a function of the PKA activity. Consistent with this observation, the serine
      rich region of ICP4 was shown to be a target for PKA in vitro. While intact ICP4
      was readily phosphorylated by ICP4 in vitro, the d8-10 mutant ICP4 was not.
      Moreover, a synthethic peptide representing a sequence in the serine tract that
      is predicted to be a substrate for PKA was phosphorylated by PKA in vitro, having
      a Km within the physiological range. These data suggest that PKA plays a role in
      viral growth through phosphorylation of one or more sites on the ICP4 molecule.

PMID- 8551564
TI  - Analysis of phosphorylation sites of herpes simplex virus type 1 ICP4.
AB  - The herpes simplex virus ICP4 protein is required for induction of early and late
      viral gene transcription as well as for repression of expression of its own gene
      and several other viral genes. Several electrophoretic forms of ICP4 have been
      observed, and phosphorylation is thought to contribute to this heterogeneity and
      possibly to the multiple functions of ICP4. To define the complexity of the
      site(s) of phosphorylation of ICP4 and to initiate mapping of this site(s), we
      have performed two-dimensional phosphopeptide mapping of wild-type and mutant
      forms of ICP4 labeled in infected cells or in vitro. Wild-type ICP4 labeled in
      infected cells shows a complex pattern of phosphopeptides, and smaller mutant
      forms of ICP4 show progressively fewer phosphopeptides, arguing that multiple
      sites on ICP4 are phosphorylated. The serine-rich region of ICP4, residues 175 to
      198, was shown to be a site for phosphorylation. Furthermore, the serine-rich
      region itself or the phosphorylation of this region increases phosphorylation of
      all phosphopeptides. A mutant ICP4 molecule lacking the serine-rich region showed
      low levels of phosphorylation by protein kinase A or protein kinase C in vitro.
      These results suggest that there may be a sequential phosphorylation of ICP4,
      with phosphorylation of the serine-rich region stimulating phosphorylation of the
      rest of the molecule. In addition, purified ICP4 showed an associated kinase
      activity or an autophosphorylation activity with properties different from those
      of protein kinase A or protein kinase C.

PMID- 8551565
TI  - CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes after
      immunization and show diminished resistance to subsequent virus challenge.
AB  - Although primary antiviral CD8+ cytotoxic T lymphocytes (CTL) can be induced in
      mice depleted of CD4+ T cells, the role of CD4+ T lymphocytes in the generation
      and maintenance of antiviral memory CTL is uncertain. This question, and the
      consequences upon vaccine-mediated protection, were investigated in transgenic
      CD4 knockout (CD4ko) mice, which lack CD4+ T lymphocytes. Infection of
      immunocompetent C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV), or
      with recombinant vaccinia viruses bearing appropriate LCMV sequences, induces
      long-lasting protective immunity, mediated mainly by antiviral CD8+ CTL. Here we
      report two important findings. First, LCMV-specific CD8+ memory CTL are
      maintained at considerably lower levels in CD4ko mice than in normal C57BL/6J
      mice; we demonstrate a reduction in precursor CTL evident as soon as 30 days
      postimmunization and declining, by day 120, to levels 1 to 2 log units below
      those in normal mice. Thus, CD4+ T cells appear to be important to the generation
      and maintenance of their CD8+ counterparts. Second, this reduction has an
      important biological consequence; compared with immunocompetent mice, CD4ko mice
      immunized with vaccinia virus recombinants expressing nucleoprotein or
      glycoprotein of LCMV are less effectively protected from subsequent LCMV
      challenge. Thus, this study underscores the potential importance of CD4+ T
      lymphocytes in generation of appropriate levels of CD(8+)-cell-mediated
      immunoprotective memory and has implications for vaccine efficacy in individuals
      with immune defects in which CD4 levels may be reduced, such as AIDS.

PMID- 8551566
TI  - Substitution of a single amino acid residue is sufficient to allow the human
      amphotropic murine leukemia virus receptor to also function as a gibbon ape
      leukemia virus receptor.
AB  - We have previously reported the unique properties of a receptor for amphotropic
      murine leukemia viruses (A-MuLVs) expressed on Chinese hamster E36 cells (C.A.
      Wilson, K.B. Farrell, and M.V. Eiden, J. Virol. 68:7697-7703, 1994). This
      receptor, HaPiT2 (formerly designated EAR), in contrast to the human form of the
      A-MuLV receptor (PiT2), functions as a receptor not only for A-MuLVs but also for
      gibbon ape leukemia virus (GALV). Comparison of the deduced amino acid sequences
      of the HaPiT2 and PiT2 proteins suggested that differences in the amino acid
      composition of the extracellular region(s) of the hamster and human proteins
      account for their functional differences. We substituted extracellular regions of
      HaPiT2 for those of PiT2 to map the region of the HaPiT2 protein required for
      GALV receptor function. Only those PiT2-HaPiT2 chimeric receptors containing the
      fourth and fifth extracellular regions of HaPiT2 functioned as GALV receptors. We
      have now determined that the substitution of a single amino acid residue,
      glutamic acid, for the lysine residue at position 522 in the fourth extracellular
      region of the PiT2 protein is sufficient to render PiT2 functional as a GALV
      receptor.

PMID- 8551567
TI  - Multidrug-resistant human immunodeficiency virus type 1 strains resulting from
      combination antiretroviral therapy.
AB  - Multidrug-resistant human immunodeficiency virus type 1 (HIV-1) strains with
      reverse transcriptase (RT) mutations at codons A62-->V, V75-->I, F77-->L, F116-
      >Y, and Q151-->M have been reported in patients receiving combination therapy
      with zidovudine (AZT) and didanosine (ddI). Infectious clones with each mutation
      alone, all five mutations together, and various combinations of mutations were
      created by site-directed mutagenesis. Mutation Q151-->M conferred partial
      resistance to AZT, ddI, zalcitibine, and stavudine, whereas a combination of four
      mutations conferred increased resistance to AZT, ddI, zalcitibine, and stavudine.
      The positions of residues 75, 77, and 151 in the three-dimensional crystal
      structure of HIV-1 RT suggest that these residues may affect the ability of the
      enzyme to discriminate between deoxynucleoside triphosphates and nucleoside
      analog RT inhibitors. Replication experiments showed that clones with mutation
      F77-->L but without V75-->I (HIV-1(77), HIV-1(77,151), and HIV-1(77,116,151) had
      attenuated growth compared with that of the original HIV-1NL4-3 strain and
      strains containing mutations at both positions 75 and 77 (HIV-1(75,77,151) and
      HIV-1(75,77,116,15)). Sequence analysis of viral RNA and proviral DNA from
      several patients indicated that RT mutations developed in a sequential and
      cumulative pattern over the course of a 2- to 4-year observation period. The
      present results suggest that drug resistance and viral replicative capacity both
      may play a role in selection of HIV-1 RT mutations.

PMID- 8551568
TI  - Identification and characterization of the bovine herpesvirus 1 UL7 gene and gene
      product which are not essential for virus replication in cell culture.
AB  - The UL7 gene of bovine herpesvirus 1 (BHV-1) strain Schonboken was found at a
      position and in a context predicted from the gene order in the prototype
      alphaherpesvirus herpes simplex virus type 1. The gene and flanking regions were
      sequenced, the UL7 RNA and protein were characterized, and 98.3% of the UL7 open
      reading frame was deleted from the viral genome without destroying productive
      virus replication. Concomitant deletion of nine 3' codons from the BHV-1 UL6 ORF
      and 77 amino acids from the carboxy terminus of the predicted BHV-1 UL8 protein
      demonstrated that these domains are also not essential for function of the
      respective proteins. The UL7 open reading frame encodes a protein of 300 amino
      acids with a calculated molecular mass of 32 kDa. Comparison with UL7 homologs of
      other alphaherpesviruses revealed a high degree of homology, the most prominent
      being to the predicted UL7 polypeptide of varicella-zoster virus, with 43.3%
      identical amino acids. A monospecific anti-UL7 serum identified the 33-kDa
      (apparent-molecular-mass) UL7 polypeptide which is translated from an early
      expressed 1.7-kb RNA. The UL7 protein was localized in the cytoplasm of infected
      cells and could not be detected in purified virions. In summary, we describe the
      first identification of an alphaherpesviral UL7-encoded polypeptide and
      demonstrate that the UL7 protein is not essential for replication of BHV-1 in
      cell culture.

PMID- 8551569
TI  - Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on
      the gp120 glycoprotein of human immunodeficiency virus type 1.
AB  - We have isolated and characterized human monoclonal antibody 2G12 to the gp120
      surface glycoprotein of human immunodeficiency virus type 1 (HIV-1). This
      antibody potently and broadly neutralizes primary and T-cell line-adapted clade B
      strains of HIV-1 in a peripheral blood mononuclear cell-based assay and inhibits
      syncytium formation in the AA-2 cell line. Furthermore, 2G12 possesses
      neutralizing activity against strains from clade A but not from clade E.
      Complement- and antibody-dependent cellular cytotoxicity-activating functions of
      2G12 were also defined. The gp120 epitope recognized by 2G12 was found to be
      distinctive; binding of 2G12 to LAI recombinant gp120 was abolished by amino acid
      substitutions removing N-linked carbohydrates in the C2, C3, V4, and C4 regions
      of gp120. This gp120 mutant recognition pattern has not previously been observed,
      indicating that the 2G12 epitope is unusual. consistent with this, antibodies
      able to block 2G12 binding to recombinant gp120 were not detected in significant
      quantities in 16 HIV-positive human serum samples.

PMID- 8551570
TI  - Circulating immunoglobulin G can play a critical role in clearance of intestinal
      reovirus infection.
AB  - Reoviruses are encapsidated double-stranded RNA viruses that cause systemic
      disease in mice after peroral (p.o.) inoculation and primary replication in the
      intestine. In this study, we define components of the immune system involved in
      the clearing of reovirus from the proximal small intestine. The intestines of
      immunocompetent adult CB17, 129, and C57BL/6 mice were cleared of reovirus
      serotype 3 clone 9 (T3C9) within 7 days of p.o. inoculation. Antigen-specific
      lymphocytes were important for the clearance of intestinal infection, since
      severe combined immunodeficient (SCID) mice failed to clear T3C9 infection. To
      define specific immune components required for intestinal clearance, reovirus
      infection of mice with null mutations in the immunoglobulin M (IgM) transmembrane
      exon (MuMT; B cell and antibody deficient) or beta 2 microglobulin gene (beta 2-/
      ; CD8 deficient) was evaluated. beta 2-/- mice cleared reovirus infection with
      normal kinetics, while MuMT mice showed delayed clearance of T3C9 7 to 11 days
      after p.o. inoculation. Adoptive transfer of splenic lymphocytes from reovirus
      immune CB17 mice inhibited growth of T3C9 in CB17 SCID mouse intestine 11 days
      after p.o. inoculation. The efficiency of viral clearance by adoptively
      transferred cells was significantly diminished by depletion of B cells prior to
      adoptive transfer. Results in SCID and MuMT mice demonstrate an important role
      for B cells or IgG in clearance of reovirus from the intestines. Polyclonal
      reovirus-immune rabbit serum, protein A-purified immune IgG, and murine
      monoclonal IgG2a antibody specific for reovirus outer capsid protein sigma 3
      administered intraperitoneally all normalized clearance of reovirus from
      intestinal tissue in MuMT mice. This result demonstrates an IgA-independent role
      for IgG in the clearance of intestinal virus infection. Polyclonal reovirus
      immune serum also significantly decreased reovirus titers in the intestines of
      SCID mice, demonstrating a T-cell-independent role for antibody in the clearance
      of intestinal reovirus infection. B cells and circulating IgG play an important
      role in the clearance of reovirus from intestines, suggesting that IgG may play a
      more prominent functional role at mucosal sites of primary viral replication than
      was previously supposed.

PMID- 8551571
TI  - The bovine papillomavirus type 1 E2 transactivator and repressor proteins use
      different nuclear localization signals.
AB  - The E2 gene of bovine papillomavirus type 1 encodes at least three nuclear
      phosphoproteins that regulate viral transcription and DNA replication. All three
      proteins have a common C-terminal domain that has DNA-binding and dimerization
      activities. A basic region in this domain forms an alpha helix which makes direct
      contact with the DNA target. In this study, it is shown that in addition to its
      role in DNA binding, this basic region functions as a nuclear localization signal
      both in the E2 DNA-binding domain and in a heterologous protein. Deletion of this
      signal sequence resulted in increased accumulation of the E2 transactivator and
      repressor proteins in the cytoplasm, but nuclear localization was not eliminated.
      In the full-length transactivator protein, another signal, present in the N
      terminal transactivation domain, is used for transport to the nucleus, and the C
      terminal nuclear localization signal(s) are masked. The use of different nuclear
      localization signals could potentially allow differential regulation of the
      subcellular localization of the E2 transactivator and repressor proteins at some
      stage in the viral life cycle.

PMID- 8551572
TI  - Marek's disease virus (MDV) ICP4, pp38, and meq genes are involved in the
      maintenance of transformation of MDCC-MSB1 MDV-transformed lymphoblastoid cells.
AB  - An antisense strategy has been used to identify genes important for the
      maintenance of transformation of MDCC-MSB1 (MSB1) Marek's disease virus
      transformed lymphoblastoid cells. Oligodeoxynucleotides antisense to the
      predicted translation initiation regions of ICP4 and pp38 mRNAs inhibited
      proliferation of MSB1 cells but not MDCC-CU91 (CU91) reticuloendotheliosis virus
      transformed cells. Control oligodeoxynucleotides having the same base composition
      but a different sequence did not inhibit MSB1 cell proliferation. In addition,
      ICP4 and pp38 antisense oligodeoxynucleotides resulted in 77- and 100-fold
      reductions in colony formation by MSB1 cells in soft agar, respectively. To
      extend and corroborate these results, a novel system based on efficiently
      regulated expression of eukaryotic genes by a chimeric mammalian transactivator,
      LAP267 (S. B. Baim, M. A. Labow, A. J. Levine, and T. Shenk, Proc. Natl. Acad.
      Sci. USA 88:5072-5076, 1991), was used. MSB1-derived stably transfected cell
      lines in which RNA antisense to Marek's disease virus ICP4, pp38, or meq could be
      induced by treatment of the cells with isopropyl-beta-D-thiogalactopyranoside
      (IPTG) were constructed. Control cell lines in which expression of ICP4 sense or
      pUC19 sequences could be induced by IPTG were also constructed. Induction of the
      cell lines indicated that ICP4 antisense RNA, but not ICP4 sense RNA or pUC19
      RNA, inhibited proliferation of MSB1 cells. Induction of ICP4, meq, or pp38
      antisense RNAs, but not ICP4 sense or pUC19 RNAs, had a dramatic effect on
      relative colony formation by MSB1 cells in soft agar. These results indicate that
      ICP4, pp38, and Meq are all involved in the maintenance of transformation of MSB1
      cells.

PMID- 8551573
TI  - Rolling circle DNA replication by extracts of herpes simplex virus type 1
      infected human cells.
AB  - Whole-cell extracts of herpes simplex virus type 1-infected human cells (293
      cells) can promote the rolling circle replication of circular duplex DNA
      molecules. The products of the reaction are longer than monomer unit length and
      are the result of semiconservative DNA replication by the following criteria: (i)
      resistance to DpnI and susceptibility to MboI restriction enzymes, (ii) shift in
      density on a CsCl gradient of the products synthesized in the presence of bromo
      dUTP to a position on the gradient consistent with those of molecules composed
      mainly of one parental DNA strand and one newly synthesized DNA strand, and (iii)
      the appearance in the electron microscope of molecules consisting of duplex
      circles with multiunit linear appendages, a characteristic of a rolling circle
      mode of DNA replication. The reaction requires ATP and is dependent on herpes
      simplex virus type 1-encoded DNA polymerase.

PMID- 8551574
TI  - Transcriptional repression of specific host genes by the mycovirus Cryphonectria
      hypovirus 1.
AB  - The hypovirus CHV1, which infects the plant-pathogenic fungus Cryphonectria
      parasitica, causes a distinct range of symptoms in its host that include reduced
      virulence expression, reduced sporulation, and reduced pigmentation. The virus,
      however, has little or no effect on fungal growth in culture. The visual symptoms
      are associated with reduced accumulation of a small number of host mRNAs and
      proteins. Four of the host genes encoding these down-regulated mRNAs have been
      characterized; they include two genes encoding a fungal sex pheromone (Vir1 and
      Vir2), a gene encoding an extracellular laccase (Lac1), and a gene encoding a
      cell wall hydrophobin (Crp). Expression of most other host proteins appears to be
      unaffected by the virus. These four genes can serve as reporter genes in studies
      of the effect of the virus on host gene expression. It is hypothesized that the
      four genes are coordinately down-regulated by the virus and probably are
      associated in a regulatory cascade. This hypothesis was tested by measuring the
      relative transcription rate of each gene in virus-infected and uninfected
      isogenic strains of the fungus by using nuclear run-on assays. The effects of the
      virus on transcription of these genes generally mirrored the observed effects of
      the virus on relative accumulation of the mRNAs of each gene. Although repressed
      transcription cannot account for all of the effects of the virus on mRNA
      accumulation of these four reporter genes, it is the predominant effect.

PMID- 8551575
TI  - A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus
      infection in B lymphocytes.
AB  - We have isolated a cDNA encoding a novel hematopoietin receptor family member
      related to the p40 subunit of interleukin-12 and to the ciliary neurotrophic
      factor receptor, whose expression is induced in B lymphocytes by Epstein-Barr
      virus (EBV) infection. This gene, which we have designated EBV-induced gene 3
      (EBI3), encodes a 34-kDa glycoprotein which lacks a membrane-anchoring motif and
      is secreted. Despite the absence of a membrane-anchoring motif and of cysteines
      likely to mediate covalent linkage to an integral membrane protein, EBI3 is also
      present on the plasma membrane of EBV-transformed B lymphocytes and of
      transfected cells. Most newly synthesized EBI3 is retained in the endoplasmic
      reticulum in an endoglycosidase H-sensitive form associated with the molecular
      chaperone calnexin and with a novel 60-kDa protein. EBI3 is expressed in vivo by
      scattered cells in interfollicular zones of tonsil tissue, by cells associated
      with sinusoids in perifollicular areas of spleen tissue, and at very high levels
      by placental syncytiotrophoblasts. EBI3 expression in vitro is induced in EBV
      negative cell lines by expression of the EBV latent infection membrane protein-1
      and in peripheral blood mononuclear cells by pokeweed mitogen stimulation. EBI3
      maps to chromosome 19p13.2/3, near genes encoding the erythropoietin receptor and
      the cytokine receptor-associated kinase, Tyk2. EBI3 synthesis by trophoblasts and
      by EBV-transformed cells and similarities to interleukin-12 p40 are compatible
      with a role for EBI3 in regulating cell-mediated immune responses.

PMID- 8551576
TI  - Apparent uncoupling of oncogenicity from fibroblast transformation and apoptosis
      in a mutant myc gene transduced by feline leukemia virus.
AB  - The T17 v-myc oncogene was transduced by feline leukemia virus in a spontaneous
      feline T-cell lymphosarcoma. Molecular cloning and sequencing of the v-myc gene
      revealed several unique mutations, including a large deletion affecting amino
      acids 49 to 124 and a 3-bp insertion within the basic DNA binding domain which
      converts Leu-362 to Phe-Arg. The T17 lymphoma cell line was found to express a
      truncated 50-kDa Myc protein at exceptionally high levels, while the endogenous c
      myc gene was not detectably expressed. These observations suggest that the mutant
      Myc product expresses an oncogenic function in T cells. Further evidence that the
      T17 mutant gene retains oncogenic potential was provided by its detection in
      clonally integrated proviruses in secondary tumors induced by feline leukemia
      virus T17, where no reversion mutations were found in any of three tumors
      examined. However, the mutant T17 v-myc gene did not induce transformation in a
      chicken embryo fibroblast assay, in contrast to wild-type feline c-myc, which
      conferred higher growth rates on the chicken fibroblasts, along with altered
      morphology and the ability to form foci in soft agar. Chicken cells over
      expressing feline c-myc died by apoptosis when cultured with low serum
      concentrations, while the T17 mutant had no discernible effect. These results
      suggest that the leukemogenic potential of Myc can be uncoupled from its ability
      to cause transformation in fibroblasts. A possible explanation for this apparent
      paradox is that developing T cells are acutely sensitive to a subset of Myc
      functions which are insufficient for fibroblast transformation.

PMID- 8551577
TI  - SR protein splicing factors interact with the Rous sarcoma virus negative
      regulator of splicing element.
AB  - Retroviral replication requires that a portion of the primary transcripts
      generated from proviral DNA be spliced to serve as mRNA for the envelope protein
      and in Rous sarcoma virus as src mRNA. However, a substantial amount of full
      length RNA must be maintained in an unspliced form, as the unspliced RNA serves
      both as mRNA for structural proteins and virion-associated enzymatic proteins and
      as genomic RNA for progeny virions. The extent of viral RNA splicing must be
      finely controlled, since only a narrow range in the ratio of unspliced RNA to
      spliced RNA is tolerated for optimal replication. A number of cis-acting
      sequences within the RNA of Rous sarcoma virus play a role in preserving a large
      pool of unspliced RNA. One such sequence, the negative regulator of splicing
      (NRS), is of interest because it blocks splicing but is not located near any of
      the splice junctions. To better understand how this novel element blocks splicing
      at a distance, we set out to identify host cell factors that interact
      specifically with this inhibitory sequence. In this study, proteins from nuclear
      extracts with molecular masses of 26, 36, 44, and 55 kDa were shown by UV cross
      linking assays to bind the NRS preferentially. One of them, p55, was also
      detected in a specific complex with SR protein electrophoretic mobility shift
      assay. All but p55 have biochemical properties consistent with SR protein
      splicing factors, and some, but not all, of the total SR proteins purified from
      HeLa cells cross-link specifically to the NRS. The strongest cross-linking SR
      protein is SRp30a/b, which is composed of the splicing factors SF2/ASF and SC35.
      The NRS specifically binds bacterially expressed SF2/ASF, whereas nonfunctional
      mutants do not. Data indicating that the 36-kDa protein which cross-links in
      nuclear extracts is SF2/ASF are presented. The data indicate that factors
      normally required for RNA splicing may be exploited by retroviruses to block
      splicing.

PMID- 8551578
TI  - Mosquito homolog of the La autoantigen binds to Sindbis virus RNA.
AB  - We have isolated a 50-kDa mosquito protein that binds with high affinity to a
      riboprobe representing the 3' end of the minus strand of Sindbis virus RNA. The
      isolated protein has been used to obtain cDNA clones encoding this protein that
      have been sequenced and used to express the protein in large amounts. Sequence
      comparisons make clear that this protein is the mosquito homolog of the La
      autoantigen. The N-terminal half of the protein shares considerable sequence
      identity with the human La protein, the rat La protein, and the recently
      identified Drosophila melanogaster homolog. There is one stretch of 100 amino
      acids in the N-terminal domain in which 48 residues are identical in all four
      proteins. In contrast, the C-terminal domain of the mosquito protein shares
      little identity with any of the other three proteins. We have also shown that the
      mosquito protein, the human protein, and a putative chicken homolog of the La
      protein cross-react immunologically and, thus, all share antigenic epitopes. The
      mosquito La protein is primarily nuclear in location, but significant amounts are
      present in the cytoplasm, as is the case for the La proteins of other species.
      The equilibrium constant for the binding of the expressed mosquito La protein to
      the Sindbis virus riboprobe is 15.4 nM, and thus the affinity of binding is high
      enough to be physiologically relevant. Furthermore, the conservation of this
      protein in the animal kingdom may be significant, because Sindbis virus utilizes
      mosquitoes, birds, and mammals as hosts. We propose that the interactions we
      observe between the La protein and toes, birds, and mammals as hosts. We propose
      that the interactions we observe between the La protein and a putative promoter
      in the Sindbis virus genome are significant for Sindbis virus RNA replication.

PMID- 8551579
TI  - Translation of Sindbis virus mRNA: analysis of sequences downstream of the
      initiating AUG codon that enhance translation.
AB  - Alphaviruses, particularly Sinbis virus and Semliki Forest virus, are proving to
      be useful vectors for the expression of heterologous genes. In infected cells,
      these self-replicating vectors (replicons) transcribe a subgenomic mRNA that
      codes for a heterologous protein instead of the structural proteins. We reported
      recently that translation of the reporter gene lacZ is enhanced 10-fold when the
      coding sequences of this gene are fused downstream of and in frame with the 5'
      half of the capsid gene (I. Frolov and S. Schlesinger, J. Virol. 68:8111-8117,
      1994). The enhancing sequences, located downstream of the AUG codon that
      initiates translation of the capsid protein, have a predicted hairpin structure.
      We have mutated this region by making changes in the codons which do not affect
      the protein sequence but should destabilize the putative hairpin structure. These
      changes caused a decrease in the accumulation of the capsid-beta-galactosidase
      fusion protein. When these alterations were inserted into the capsid gene in the
      context of the intact Sindbis virus genome, they led to a decrease in the rate of
      virus formation but did not affect the final yield. We also altered the original
      sequence to one that has 12 contiguous G.C base pairs and should form a stable
      hairpin. The new sequence was essentially as effective as the original had been
      in enhancement of translation and in the rate of virus formation. The position of
      the predicted hairpin structure is important for its function; an insertion of 9
      nucleotides or a deletion of 9 nucleotides decreased the level of translation.
      The insertion of a hairpin structure at a particular location downstream of the
      initiating AUG appears to be a way that alphaviruses have evolved to enhance
      translation of their mRNA, and, as a consequence, they produce high levels of the
      structural proteins which are needed for virus assembly. This high level of
      translation requires an intracellular environment in which host cell protein
      synthesis is inhibited.

PMID- 8551581
TI  - Interaction between T antigen and TEA domain of the factor TEF-1 derepresses
      simian virus 40 late promoter in vitro: identification of T-antigen domains
      important for transcription control.
AB  - The large tumor antigen (TAg) of simian virus 40 regulates transcription of the
      viral genes. The early promoter is repressed when TAg binds to the origin and DNA
      replication begins, whereas the late promoter is activated by TAg through both
      replication-dependent and -independent mechanisms. Previously it was shown that
      activation is diminished when a site in the viral enhancer to which the factor
      TEF-1 binds is disrupted. We show here that the NH2-terminal region of TAg binds
      to the TEA domain of TEF-1, a DNA binding domain also found in the Drosophila
      scalloped and the Saccharomyces cerevisiae TEC1 proteins. The interaction
      inhibits DNA binding by TEF-1 and activates transcription in vitro from a subset
      of naturally occurring late start sites. These sites are also activated by
      mutations in the DNA motifs to which TEF-1 binds. Therefore, TEF-1 appears to
      function as a repressor of late transcription, and its involvement in the early
      to-late shift in viral transcription is discussed. The mutation of Ser-189 in
      TAg, which reduces transformation efficiency in certain assays, disrupts the
      interaction with TEF-1. Thus, TEF-1 might also regulate genes involved in growth
      control.

PMID- 8551580
TI  - The major transcriptional transactivation domain of simian virus 40 large T
      antigen associates nonconcurrently with multiple components of the
      transcriptional preinitiation complex.
AB  - Simian virus 40 (SV40) large T antigen (Tag) is a promiscuous transcriptional
      transactivator; however, its mechanism of transactivation remains unknown. Recent
      studies have suggested the possible involvement of protein-protein interactions
      with TBP, the TATA box-binding protein of TFIID, and TEF-1, an enhancer-binding
      factor. We show here that (i) the Tag domain containing amino acids 133 to 249
      directly interacts with the general transcription factor TFIIB, the activator
      protein Sp1, and the 140-kDa subunit of RNA polymerase II, as well as with TBP
      and TEF-1; (ii) these interactions can also occur when these transcription
      factors are present in their functional states in cellular extracts; (iii)
      binding of Tag to TBP is eliminated by preincubation of TBP either at 48 degrees
      C or with the adenovirus 13S E1a protein; (iv) this domain of Tag cannot bind
      concurrently to more than one of these transcription factors; and (v) the
      substitution of Tag amino acid residues 173 and 174 inactivates the ability of
      this Tag domain both to associate with any of these transcription factors and to
      transactivate the SV40 late promoter. Thus, we conclude that SV40 Tag probably
      does not transactivate via the concurrent interaction with multiple components of
      the preinitiation complex. Rather, we hypothesize that transactivation by Tag may
      primarily occur by removing or preventing the binding of factors that inhibit the
      formation of preinitiation complexes.

PMID- 8551582
TI  - Replication properties of dUTPase-deficient mutants of caprine and ovine
      lentiviruses.
AB  - The virion-associated dUTPase activities of caprine arthritis-encephalitis virus
      (CAEV) and visna virus were determined by using an assay which measure the actual
      ability of the dUTPase to prevent the dUTP misincorporations into cDNA during
      reverse transcription. We showed that the CAEV molecular clone from the Cork
      isolate was dUTPase defective as a result of a single amino acid substitution.
      Using this point mutant and deletion mutants of CAEV as well as a deletion mutant
      of visna virus, we demonstrated that dUTPase-deficient viruses replicate
      similarly to wild-type viruses in dividing cells but show delayed replication in
      nondividing primary macrophages.

PMID- 8551583
TI  - Interactions between the two surface proteins of rotavirus may alter the receptor
      binding specificity of the virus.
AB  - The infection of target cells by most animal rotavirus strains requires the
      presence of sialic acids (SAs) on the cell surface. We recently isolated variants
      from simian rotavirus RRV whose infectivity is no longer dependent on SAs and
      showed that the mutant phenotype segregates with the gene coding for VP4, one of
      the two surface proteins of rotaviruses (the other one being VP7). The nucleotide
      sequence of the VP4 gene of four independently isolated variants showed three
      amino acid changes, at positions 37 (Leu to Pro), 187 (Lys to Arg), and 267 (Tyr
      to Cys), in all mutant VP4 proteins compared with RRV VP4. The characterization
      of revertant viruses from two independent mutants showed that the arginine
      residue at position 187 changed back to lysine, indicating that this amino acid
      is involved in the determination of the mutant phenotype. Surprisingly, sequence
      analysis of reassortant virus DS1XRRV, which depends on SAs to infect the cell,
      showed that its VP4 gene is identical to the VP4 gene of the variants. Since the
      only difference between DS1XRRV and the RRV variants is the parental origin of
      the VP7 gene (human rotavirus DS1 in the reassortant), these findings suggest
      that the receptor-binding specificity of rotaviruses, via VP4, may be influenced
      by the associated VP7 protein.

PMID- 8551585
TI  - Cooperative assembly of EBNA1 on the Epstein-Barr virus latent origin of
      replication.
AB  - The EBNA1 protein of Epstein-Barr virus (EBV) activates DNA replication by
      binding to multiple copies of its 18-bp recognition sequence present in the
      Epstein-Barr virus latent origin of DNA replication, oriP. Using electrophoretic
      mobility shift assays, we have localized the minimal DNA binding domain of EBNA1
      to between amino acids 470 and 607. We have also demonstrated that EBNA1
      assembles cooperatively on the dyad symmetry subelement of oriP and that this
      cooperative interaction is mediated by residues within the minimal DNA binding
      and dimerization domain of EBNA1.

PMID- 8551584
TI  - The M1 gene is associated with differences in the temperature optimum of the
      transcriptase activity in reovirus core particles.
AB  - The reovirus core is a multienzyme complex that contains five different
      structural proteins and 10 segments of double-stranded RNA. The core is
      responsible for transcribing mRNA from the enclosed double-stranded RNA. The
      reovirus transcriptase has an unusual temperature profile, with optimum
      transcription occurring at approximately 50 degrees C and little activity
      occurring below 30 or above 60 degrees C. Purified reovirus serotype 1 Lang (T1L)
      cores transcribed most efficiently at 48 degrees C. The transcriptase temperature
      optimum of purified reovirus serotype 3 Dearing (T3D) cores was 52 degrees C. In
      addition, T1L cores produced more mRNA per particle than did T3D cores at their
      respective temperature optima. Core particles were purified from T1L x T3D
      reassortants and were used to map these differences. The M1 gene, which encodes
      minor core protein mu 2, was uniquely associated with the difference in
      temperature optimum of transcription (P = 0.0003). The L1 gene, which encodes
      minor core protein lambda 3 (previously implicated as the RNA polymerase), and
      the M1 gene were associated with the difference in absolute amounts of transcript
      produced (P = 0.01 and P = 0.0002, respectively). These data suggest that minor
      core protein mu 2 also plays a role in reovirus transcription.

PMID- 8551586
TI  - Mutational analysis of influenza B virus RNA transcription in vitro.
AB  - The roles of the 3'- and 5'-terminal nucleotides and the panhandle structure of
      influenza B virus virion RNA were analyzed in vitro by transcription of model RNA
      templates with influenza B virus RNA polymerase. The results suggest that the
      stability of the panhandle and breathing of the extreme ends of the panhandle are
      important factors for efficient transcription. Influenza B virus polymerase
      appears to be more tolerant of mutations in the panhandle structure than
      influenza A virus polymerase. This is consistent with the greater degree of
      heterogeneity observed naturally in the 3'-terminal nucleotides of the virion RNA
      of influenza B virus than in influenza A virus.

PMID- 8551587
TI  - The UL49.5 gene of pseudorabies virus codes for an O-glycosylated structural
      protein of the viral envelope.
AB  - Sequence analysis of BamHI fragment 1 of the pseudorabies virus (PrV) genome
      identified a novel PrV gene located upstream of the UL50 gene encoding PrV
      dUTPase. The deduced protein product displayed homology to the product of the
      herpes simplex virus type 1 UL49.5 protein. The predicted PrV UL49.5 protein
      consists of 98 amino acids with a calculated molecular mass of 10,155 Da. It
      contains putative signal peptide and transmembrane domains but lacks a consensus
      sequence for N glycosylation. PrV UL49.5 was expressed as a fusion protein with
      glutathione S-transferase in Escherichia coli, and a rabbit antiserum was
      generated. In Western blots (immunoblots) of purified virions, the antiserum
      detected a protein with an apparent molecular mass of 14 kDa. After fractionation
      of the virions, the 14-kDa protein was detected in the envelope fraction.
      Localization of the UL49.5 protein in the viral envelope was confirmed by
      immunoelectron microscopy. The treatment of purified virions with glycosidases
      led to a reduction of the apparent molecular mass in Western blots by
      approximately 2 kDa following digestion with neuraminidase and O-glycosidase. Our
      results demonstrate that the PrV UL49.5 protein is an O-glycosylated structural
      component of the viral envelope. It represents the 10th PrV glycoprotein
      described. According to the unified nomenclature for alphaherpesvirus
      glycoproteins, we propose to designate it glycoprotein N (gN).

PMID- 8551588
TI  - Identification and characterization of pseudorabies virus dUTPase.
AB  - Sequence analysis within the long segment of the pseudorabies virus (PrV) genome
      identified an open reading frame of 804 bp whose deduced protein product of 268
      amino acids exhibited homology to dUTPases of other herpesviruses. The gene was
      designated UL50 because of its colinearity with the homologous gene of herpes
      simplex virus type 1. An antiserum raised against a bacterially expressed
      fragment of PrV UL50 specifically detected a 33-kDa protein in lysates of
      infected cells, which is in agreement with the predicted molecular mass of the
      PrV UL50 protein. A UL50-negative PrV mutant (PrV UL50-) was constructed by the
      insertion of a beta-galactosidase expression cassette into the UL50 coding
      sequence. A corresponding rescuant (PrV UL50resc) was also isolated. The
      interruption of the UL50 gene led to the disappearance of the 33-kDa protein,
      whereas restoration of UL50 gene expression restored detection of the 33-kDa
      protein. Enzyme activity assays confirmed that UL50 of PrV codes for a dUTPase
      which copurifies with nuclei of infected cells. PrV UL50- replicated with an only
      slightly reduced efficiency in epithelial cells in culture compared with that of
      its parental wild-type virus strain. Our results thus demonstrate that UL50 of
      PrV encodes a protein of 33 kDa with dUTPase activity which copurifies with
      nuclei of infected cells and is dispensable for replication in cultured
      epithelial cells.

PMID- 8551589
TI  - Major histocompatibility complex class II I-E-independent transmission of C3H
      mouse mammary tumor virus.
AB  - C57BL/6 mice are resistant to C3H mouse mammary tumor virus (MMTV)-induced
      mammary tumorigenesis and lack major histocompatibility complex class II I-E
      molecules that are essential for presentation of C3H superantigen to T cells. T
      cells are needed for transmission of milk-borne MMTV from the gut to the mammary
      gland. In this report, we show that infectious C3H MMTV is produced by C57BL/6
      mice that nurse on C3H mothers but that virus production in the mammary gland is
      delayed compared with that in I-E+ mouse strains.

PMID- 8551590
TI  - Productive persistent infection of hematopoietic cells by human foamy virus.
AB  - Human foamy virus can establish persistent infections in human hematopoietic cell
      lines, such as H92.1.7 (erythroblastoid cells), Jurkat (CD4+ T cells), and U937
      (myeloid-monocytic cells). The infection is characterized by constant production
      of infectious viruses (for > 2 1/2 years) with no cytopathic effects on the host
      cells. Electron microscopy of the infected cells showed a viral morphology
      similar to that observed for particles produced after acute infection. We have
      detected, in addition to the full-length form of bel1, a previously described
      deletion in the bel1 gene of the proviral DNA in these cells. RNA containing this
      301-bp deletion, which mapped to the splice donor and acceptor sites of the
      intron of the bet gene, was also found in encapsidated virion RNA. However, the
      presence of this defective provirus harboring the deletion in bel1 does not
      prevent productive persistence in these chronically infected cells, since the
      virus titer does not decrease during cultivation.

PMID- 8551591
TI  - Effect of E2 envelope glycoprotein cytoplasmic domain mutations on Sindbis virus
      pathogenesis.
AB  - The cytoplasmic domain of the E2 envelope glycoprotein is important in Sindbis
      virus assembly, but little is known about its role in the pathogenesis of Sindbis
      virus encephalitis. To investigate its role in viral pathogenesis, we constructed
      six recombinant viruses containing site mutations in the E2 cytoplasmic domain,
      using the neurovirulent background strain, TE12. Our findings demonstrate that
      the E2 cytoplasmic domain is a determinant of Sindbis virus growth and
      neurovirulence in suckling mice as well as persistent infection in weanling scid
      mice. They also suggest that the tyrosine, serine, or threonine residues are not
      essential for replication in mouse brain or anti-E2 monoclonal antibody-mediated
      restriction of Sindbis virus replication.

PMID- 8551592
TI  - Processing of rabbit hemorrhagic disease virus polyprotein.
AB  - Expression of rabbit hemorrhagic disease virus (RHDV) cDNAs in vitro with rabbit
      reticulocyte lysates and in Escherichia coli have been used to study the
      proteolytic processing of RHDV polyprotein encoded by ORF1. An epitope tag was
      used for monitoring the gene products by a specific antibody. We have identified
      four gene products with molecular masses of 80, 43, 73, and 60 kDa, from the
      amino to the carboxy terminus of the polyprotein. The amino-terminal sequences of
      the 43- and 73-kDa products were determined and indicated that RHDV 3C proteinase
      cleaved Glu-Gly peptide bonds.

PMID- 8551593
TI  - Homomeric interactions between transmembrane proteins of Moloney murine leukemia
      virus.
AB  - We have studied homomeric interactions between transmembrane proteins (TM) of the
      Moloney murine leukemia virus envelope using the Saccharomyces cerevisiae two
      hybrid system. TM interacts strongly with itself but not with various control
      proteins. Deletional and mutational analyses indicated that the putative leucine
      zipper motif in the extracellular domain of TM is essential and sufficient to
      mediate the binding. The first three repeats of the leucine zipper-like motif are
      the most important in mediating the interaction. The TM-TM interaction detected
      in this system may play a role in several stages of viral replication.

PMID- 8551594
TI  - Reactivation of thymidine kinase-defective herpes simplex virus is enhanced by
      nucleoside.
AB  - Herpes simplex virus (HSV) mutants defective for thymidine kinase expression (TK
      ) have been reported to establish latent infection of sensory ganglia of mice, in
      that HSV latency-associated transcript is expressed, but to be defective for
      reactivation. In the present study, the mechanism of defective reactivation by TK
      HSV was investigated. Latent infection established by each of three reactivation
      defective HSV type 1 mutants was studied. Reactivation in explant culture was
      markedly enhanced by the addition of thymidine (dTdR) to the explant culture
      medium. Without added dTdR, reactivation occurred in 0 of 32 ganglia, while when
      dTdR (200 microM) was present, reactivation occurred in 32 of 37 ganglia (86%).
      Reactivation was minimal or did not occur after treatment with other nucleosides;
      specificity for dTdR would suggest the importance of dTdR nucleotide levels
      rather than more general nucleotide pool imbalance. Enhanced reactivation by dTdR
      was dose dependent and was blocked by acyclovir. While some degree of inhibition
      of TK- HSV by acyclovir may be expected, the complete block of dTdR-enhanced
      reactivation was unexpected. This result may suggest that HSV is particularly
      vulnerable during initial reactivation events. The mechanism of dTdR-enhanced
      reactivation of TK- HSV was further evaluated during in vivo infection by TK-
      HSV. For mice infected with TK- HSV, virus was undetectable in ganglia 3 days
      later. However, for mice infected with TK- HSV and treated with dTdR, virus was
      readily detected (2.8 x 10(3) PFU per ganglion). This result suggested that in
      vivo treatment with dTdR enhanced replication of TK- HSV in ganglion neurons. In
      turn, this suggests that in latently infected ganglia, dTdR-enhanced reactivation
      of TK- HSV occurred as a result of viral replication in neurons following initial
      reactivation events.

PMID- 8551595
TI  - Protective antibody therapy is associated with reduced chemokine transcripts in
      herpes simplex virus type 1 corneal infection.
AB  - Herpes simplex virus type 1 (HSV-1) infection on the murine cornea induces an
      intense inflammatory response which can lead to blindness. This disease, known as
      herpes stromal keratitis, can be prevented by the timely passive transfer of
      monoclonal antibody specific for viral glycoprotein D (gD). Precisely how
      antibody treatment prevents excessive corneal inflammation is not known. In this
      study we investigated whether chemokine mRNA expression is inhibited by antibody
      treatment. Total cellular RNAs isolated from normal corneas and at various times
      after virus infection were analyzed via reverse transcription-PCR for mRNA coding
      for seven different chemokines. Constitutive levels of IP-10, KC, MIP-2, MCP-1,
      MIP-1 beta, and RANTES mRNA were detected in uninfected corneas of BALB/c mice.
      When the cornea was mechanically traumatized, message for all six chemokines was
      transiently elevated above constitutive levels. In contrast, HSV-1 infection
      resulted in prolonged enhanced chemokine message expression. The kinetics of mRNA
      accumulation was distinctive for each chemokine analyzed. MIP-1 alpha message,
      not detected constitutively, was not evident until day 7 postinfection.
      Administration of anti-HSV gD monoclonal antibody 1 day after infection was
      associated with reduced message for MIP-2, MCP-1, MIP-1 alpha, and MIP-1 beta. IP
      10, KC, and RANTES messages were not altered. Collectively, our results suggest
      that anti-gD treatment may protect, at least in part, by inhibiting production of
      chemokines believed to promote inflammation.

PMID- 8551596
TI  - Nuclear preservation and cytoplasmic degradation of human immunodeficiency virus
      type 1 Rev protein.
AB  - Rev, a major regulatory protein of human immunodeficiency virus type 1, has been
      demonstrated to shuttle between the nucleus and cytoplasm of infected cells. The
      fate of the Rev protein in living cells was evaluated by pulse-chase experiments
      using a transient Rev expression system. Sixteen hours after chasing with
      unlabelled amino acids, 45% of the labelled Rev was still present, which clearly
      indicates a long half-life of Rev in living cells. A Rev mutant which is
      deficient in the ability to migrate from the nucleus to the cytoplasm was
      degraded more slowly than the wild-type Rev protein. As well, another Rev mutant
      protein, which lacks a functional nucleolar targeting signal (NOS) and is unable
      to enter the cell nucleus, was rapidly degraded and undetectable 16 h after
      chasing. Nuclear-nucleolar targeting properties provided by a divergent NOS from
      a related retrovirus, which was used to substitute for the NOS of Rev, increased
      the intracellular half-life of this Rev mutant. Moreover, coexpression of an
      intracellular anti-Rev single-chain antibody (SFv), which has been shown to
      interfere with the nuclear translocation of Rev, accelerated the degradation of
      the wild-type Rev protein. Differential degradation of Rev in the nucleus and
      cytoplasm may play a critical role in determining and maintaining different
      stages of human immunodeficiency virus type 1 infection, in conjunction with the
      shuttling properties of the Rev protein.

PMID- 8551597
TI  - Immune CD4+ T cells promote the clearance of influenza virus from major
      histocompatibility complex class II -/- respiratory epithelium.
AB  - The experiments described establish that CD4+ T-cell-dependent effector
      mechanisms can eliminate an H3N2 influenza A virus from lung cells that are
      unable to express class II major histocompatibility complex (MHC) glycoproteins.
      Radiation chimeras were made by using CD4+ T cells and bone marrow from CD8
      depleted, MHC class II +/+ mice and irradiated (950 rads) MHC class II -/-
      recipients. The influenza virus-specific CD4+ T-cell responses in these +/+-->-/-
      mice were not obviously different from those in the +/+-->+/+ controls: the
      cytokine profiles, the spectra of plasma cells producing the various
      immunoglobulin isotypes, and the frequencies of virus-specific CD4+ T cells were
      similar for the two groups. Expression of class II MHC glycoproteins on
      stimulator cells, B lymphocytes, and monocytes/macrophages is apparently
      sufficient for CD4+ T cells to terminate influenza virus infection of MHC class
      II -/- respiratory epithelium. A possible explanation is that the local spread of
      this lytic virus in the lung is limited by cytokines and/or antibody.

PMID- 8551598
TI  - Immune system-dependent and -independent replication of the scrapie agent.
AB  - Using the severe combined immunodeficiency (SCID) mouse model, we investigated
      the requirement of the immune system for the development of scrapie after
      peripheral inoculation. A total of 33% of SCID mice, all but one immunologically
      reconstituted SCID mice (93%), and all CB17 control mice developed the disease.
      PrPres was detectable in the brains of all diseased animals and in the spleens of
      reconstituted SCID and CB17 control mice but not of the diseased non
      immunologically reconstituted SCID mice. The immune system appears to be a
      primary target in the pathogenesis of scrapie, but direct spread to the central
      nervous system from the peritoneum via visceral nerve fibers can probably also
      occur.

PMID- 8551599
TI  - Infection of primary human fetal astrocytes by human herpesvirus 6.
AB  - Human herpesvirus 6 (HHV-6) is a lymphotropic betaherpesvirus which productively
      infects human CD4+ T cells and monocytes. HHV-6 is the etiologic agent for
      exanthem subitum (roseola), and it is well-known that central nervous system
      complications occur frequently during the course of HHV-6-associated disease. In
      addition, HHV-6 has been associated with encephalitis or encephalopathy. However,
      very little is known about its tropism for neural cells. There are reports that
      HHV-6 may infect some glial cell lines, but whether it can infect any primary
      neural cells is not known. Our studies show that both HHV-6A (GS) and HHV-6B (Z
      29) can infect highly purified primary fetal astrocytes in vitro. Infected cells
      showed cytopathic effects, forming giant syncytia. In dual immunofluorescence
      assays, the infected cells were detected by antibodies against the HHV-6 p41
      nuclear antigen and glial fibrillary acidic protein, indicating that the infected
      cells are indeed astrocytes. PCR and Northern (RNA) blot analyses also confirmed
      that the astrocytes are infected by HHV-6. The progeny virus did not alter its
      host range and could reinfect T cells as well as primary astrocytes. These
      findings suggest that infection of primary human astrocytes may play a role in
      the neuropathogenesis of HHV-6.

PMID- 8551600
TI  - Human immunodeficiency virus type 1 tropism for T-lymphoid cell lines: role of
      the V3 loop and C4 envelope determinants.

PMID- 8551601
TI  - Cooperative effects of the human immunodeficiency virus type 1 envelope variable
      loops V1 and V3 in mediating infectivity for T cells.
AB  - Insertion of T-cell line-tropic V3 and V4 loops from the HXB2 strain into the
      macrophage-tropic YU-2 envelope resulted in a virus with delayed infectivity for
      HUT78 and Jurkat cells compared with HXB2. Sequence analysis of viral DNA derived
      from long-term cultures of Jurkat cells revealed a specific mutation that changed
      a highly conserved Asn residue in the V1 loop of Env to an Asp residue (N-136-
      >D). Introduction of this mutation into clones containing a T-cell line-tropic V3
      loop, either with or without a T-cell line-tropic V4 loop, resulted in viruses
      that replicated to high levels in Jurkat cells and peripheral blood lymphocytes.
      The Env proteins from these constructs were expressed with the vaccinia virus/T7
      hybrid system and were found to be translated, processed, and cleaved and to bind
      to soluble CD4 similar to the wild-type HXB2 and YU-2 Env proteins. Env-mediated
      fusion with HeLa T4+ cells, however, was regulated by both the altered V1 loop
      and T-cell line-tropic V3 loop. These results suggest that subsequent to the
      initial gp120-CD4 binding event, a functional interaction can occur between the
      altered V1 loop and T-cell line-tropic V3 loop that results in infection of
      Jurkat cells and peripheral blood lymphocytes.

PMID- 8551602
TI  - Analysis of a nuclear localization signal of simian virus 40 major capsid protein
      Vp1.
AB  - The nuclear localization signal of the major structural protein, Vp1, of simian
      virus 40 was further defined by mutagenesis. The targeting activity was examined
      in cells microinjected with SV-Vp1 variant viral DNAs bearing either an
      initiation codon mutation of the agnoprotein or mutations in the Vp1 coding
      sequence or microinjected with pSG5-Vp1 and pSG5-Vp1 mutant DNAs in which Vp1 or
      mutant Vp1 is expressed from simian virus 40 early promoter. The Vp1 nuclear
      localization signal functioned autonomously without agno-protein once the Vp1
      protein was synthesized in the cytoplasm. The targeting activity was localized to
      the amino-terminal 19 residues. While replacement of cysteine 10 with glycine,
      alanine, or serine did not affect the activity, replacement of arginine 6 with
      glycine caused the cytoplasmic phenotype. When multiple mutations were introduced
      among residue 5, 6, 7, 16, 17, or 19, the targeting activity was found to reside
      in two clusters of basic residues, a cluster of lysine 5, arginine 6, and lysine
      7 and a cluster of lysine 16, lysine 17, and lysine 19. The clusters are
      independently important for nuclear localization activity.

PMID- 8551603
TI  - Mutational analysis of human papillomavirus type 16 E6 demonstrates that p53
      degradation is necessary for immortalization of mammary epithelial cells.
AB  - We have previously demonstrated that normal human mammary epithelial cells (MECs)
      are efficiently immortalized by human papillomavirus type 16 (HPV16) E6. HPV16 E6
      binds to and induces p53 degradation in vitro and induces a marked reduction of
      p53 protein in MECs. Low-risk HPV6 E6 is defective for p53 binding and
      degradation in vitro but immortalized MECs at low efficiency. The HPV6 E6
      immortalized MECs had markedly reduced levels of p53. To directly investigate
      whether the ability of HPV16 E6 to stimulate p53 degradation is required for E6
      induced immortalization, a series of HPV16 E6 mutants were analyzed for the
      ability to bind and degrade p53 in vitro, induce a reduction in p53 levels in
      vivo, and immortalize MECs. We observed that one set of mutants efficiently
      immortalized MECs, caused a reduction in p53 levels in vivo, and degraded p53 in
      vitro. Other mutants immortalized MECs with low efficiency and either induced p53
      degradation at low levels or were unable to induce p53 degradation in vitro;
      however, all of the immortal clones displayed low levels of p53. A third class of
      mutants did not immortalize MECs and failed to induce a reduction in p53 levels
      in vivo or degrade p53 in vitro. These results demonstrate that a reduction in
      p53 protein levels due to enhanced degradation is essential for MEC
      immortalization by HPV16 E6.

PMID- 8551604
TI  - The molecular target of bicyclams, potent inhibitors of human immunodeficiency
      virus replication.
AB  - Bicyclams are a novel class of antiviral compounds which act as potent and
      selective inhibitors of the replication of human immunodeficiency virus type 1
      (HIV-1) and HIV-2. They block an early step in the viral life cycle following
      adsorption to the CD4 receptor and preceding reverse transcription. To identify
      the molecular target of these compounds, we genetically analyzed variants of the
      HIV-1 molecular clone NL4-3, which developed resistance against two structurally
      related bicyclams, JM2763 and the more potent SID791. The resistant strains were
      obtained after long-term passaging in MT-4 cells in the presence of progressively
      increasing compound concentrations. Recombinants between selected genes of the
      resistant strains and the parental NL4-3 provirus were generated by adapting the
      marker rescue technique to MT-4 cells. The bicyclam-resistant phenotype was
      rescued by transferring the envelope gp120 gene of bicyclam-resistant virus into
      the NL4-3 parental genetic background. In the gp120 genes of the resistant
      strains, we identified several mutations leading to amino acid substitutions in
      the V3 loop. Furthermore, two substitutions of highly conserved amino acids in
      close proximity to the disulfide bridges of the V3 and V4 loops were found in
      both SID791- and JM2763-resistant strains. Additional mutations in regions
      encoding V3, C4, V5, and C5 were present in SID791-resistant viruses.
      Recombination experiments with overlapping parts of the envelope gene indicated
      that most, if not all, of the mutations were necessary to develop the fully
      SID791 resistant phenotype. The mutations in the C-terminal part of gp120
      downstream of the V3 loop sequence conferred partial resistance to JM2763 but did
      not significantly decrease susceptibility to SID791. The genetic data and the
      biological properties of the resistant viruses point to inhibition of entry and
      fusion as the mode of action of the HIV-inhibitory bicyclams. A possible
      mechanism of binding of bicyclams to gp120 leading to inhibition of unfolding of
      gp120 and its shedding from the gp41 fusion domain is discussed.

PMID- 8551605
TI  - Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA
      glycosylase DNA repair enzyme.
AB  - The role of the accessory gene product Vpr during human immunodeficiency virus
      type 1 infection remains unclear. We have used the yeast two-hybrid system to
      identify cellular proteins that interact with Vpr and could be involved in its
      function. A cDNA clone which encodes the human uracil DNA glycosylase (UNG), a
      DNA repair enzyme involved in removal of uracil in DNA, has been isolated.
      Interaction between Vpr and UNG has been demonstrated by in vitro protein-protein
      binding assays using translated, radiolabeled Vpr and UNG recombinant proteins
      expressed as a glutathione S-transferase fusion protein. Conversely, purified UNG
      has been demonstrated to interact with Vpr recombinant protein expressed as a
      glutathione S-transferase fusion protein. Coimmunoprecipitation experiments
      confirmed that Vpr and UNG are associated within cells expressing Vpr. By using a
      panel of C- and N-terminally deleted Vpr mutants, we have determined that the
      core protein of Vpr, spanning amino acids 15 to 77, is involved in the
      interaction with UNG. We also demonstrate by in vitro experiments that the
      enzymatic activity of UNG is retained upon interaction with Vpr.

PMID- 8551606
TI  - A 5'-proximal RNA sequence of murine coronavirus as a potential initiation site
      for genomic-length mRNA transcription.
AB  - Coronavirus transcription is a discontinuous process, involving interactions
      between a trans-acting leader and the intergenic transcription initiation
      sequences. A 9-nucleotide (nt) sequence (UUUAUAAAC), which is located immediately
      downstream of the leader at the 5' terminus of the mouse hepatitis virus (MHV)
      genomic RNA, contains a sequence resembling the consensus intergenic sequence
      (UCUAAAC). It has been shown previously that the presence of the 9-nt sequence
      facilitates leader RNA switching and may enhance subgenomic mRNA transcription.
      It is unclear how the 9-nt sequence exerts these functions. In this study, we
      inserted the 9-nt sequence into a defective interfering (DI) RNA reporter system
      and demonstrated that mRNA transcription could be initiated from the 9-nt
      sequence almost as efficiently as from the intergenic sequence between genes 6
      and 7. Sequence analysis of the mRNAs showed that the 9-nt sequence served as a
      site of fusion between the leaders and mRNA. The transcription initiation
      function of the 9-nt sequence could not be substituted by other 5'-terminal
      sequences. When the entire 5'-terminal sequence, including four copies of the
      UCUAA sequence plus the 9-nt sequence, was present, transcription could be
      initiated from any of the UCUAA copies or the 9-nt sequence, resulting in
      different copy numbers of the UCUAA sequence and the deletion of the 9-nt
      sequence in some mRNAs. All of these heterogeneous RNA species were also detected
      from the 5'-terminal region of the viral genomic-length RNA in MHV-infected
      cells. These results thus suggest tha the heterogeneity of the copy number of
      UCUAA sequences at the 5' end, the deletion of the 9-nt sequence in viral and DI
      RNAs, and the leader RNA switching are the results of transcriptional initiation
      from the 9-nt site. They also show that an mRNA species (mRNA 1) that lacks the 9
      nt sequence can be synthesized during MHV infection. Therefore, MHV genomic RNA
      replication and mRNA 1 transcription may be distinguishable.

PMID- 8551607
TI  - Effects of 3'-deoxynucleoside 5'-triphosphate concentrations on chain termination
      by nucleoside analogs during human immunodeficiency virus type 1 reverse
      transcription of minus-strand strong-stop DNA.
AB  - We have compared the effects of nucleoside analogs in quiescent and
      phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC)
      exposed to human immunodeficiency virus type 1 (HIV-1) with those of their
      triphosphorylated derivatives in cell-free HIV-1 reverse transcription assays. We
      observed a substantial decrease in synthesis of early minus-strand proviral DNA
      products in HIV-1-infected, quiescent PBMC exposed to each of 3'-azido-3'
      deoxythymidine (AZT), 2',3'-dideoxyinosine (ddI), and 2',3'-dideoxy-3'
      thiacytidine (3TC), in comparison with nontreated, infected controls. In
      contrast, no such diminution was observed when PHA-stimulated, HIV-1-infected
      PBMC were treated with the same drugs. This result was attributed to previously
      reported findings that PHA-stimulated PBMC possessed larger deoxynucleoside
      triphosphate (dNTP) pools than quiescent cells did. To further investigate this
      subject, a cell-free HIV-1 reverse transcription reaction involving HIV-1 RNA
      genomic template, recombinant purified HIV-1 reverse transcriptase, all four
      dNTPs and either tRNA3Lys or a deoxyoligonucleotide as primer was used to monitor
      chain termi-nation mediated by 2',3'-dideoxynucleoside triphosphates (ddNTPs)
      during synthesis of minus-strand strong-stop DNA. Augmented chain termination was
      observed with decreasing concentrations of both ddNTP and dNTP when the ratio of
      dNTP to ddNTP was fixed. We also found that both the number and strength of
      reverse transcription pause sites were increased at low concentrations of dNTPs
      and when a deoxyoligonucleotide primer was used in place of the cognate primer,
      tRNA3Lys. Preferential incorporation of ddATP was observed dur-ing reverse
      transcription opposite a distinct pause site in a short synthetic RNA template.
      These results con-firm the notion that the antiviral activities of ddNTP are
      dependent on both cellular dNTP pools and the state of cellular activation.
      Pausing of HIV-1 reverse transcriptase during reverse transcription, altered by
      dNTP concentrations, may be a mechanism that controls the position and extent of
      incorporation of nucleoside analogs.

PMID- 8551608
TI  - Human immunodeficiency virus type 1 integrase mutants retain in vitro integrase
      activity yet fail to integrate viral DNA efficiently during infection.
AB  - The viral integrase (IN) protein is the only viral protein known to be required
      for integration of the human immunodeficiency virus type 1 (HIV-1) genome into
      the host cell DNA, a step in the viral life cycle that is essential for viral
      replication. To better understand the relationship between in vitro IN activity
      and IN-mediated integration of viral DNA in an infected cell, we characterized
      the effects of 13 IN mutations on viral replication in cultured cells. Using HIV
      1 genomes that express the hygromycin resistance gene and do not express the HIV
      1 env gene, we generated stocks of pseudotype virus coated with the murine
      leukemia virus amphotropic envelope glycoprotein, containing either wild-type or
      mutant HIV-1 IN. All mutants produced normal amounts of physical particles, as
      measured by reverse transcriptase activity and capsid protein (p24)
      concentration, but they formed three groups based on infectious titer and
      synthesis of viral DNA. Changes at the three highly conserved acidic residues in
      the IN core domain (D-64, D-116, and E-152) impair provirus formation without
      affecting viral DNA synthesis or the accumulation of viral DNA in the nucleus of
      the infected cell, a phenotype predicted by each mutant's lack of in vitro
      integrase activity. Mutations at positions N-120, R-199, and W-235 minimally
      affect in vitro integrase activity, but infectious titers are severely reduced,
      despite normal synthesis of viral DNA, implying a defect during integration in
      vivo. Mutations in the zinc binding region (H12C, H16V, and H16C), S81R, and a
      deletion of residues 32 through 275 yield noninfectious particles that synthesize
      little or no viral DNA following infection, despite wild-type levels of reverse
      transcriptase activity and viral RNA in the particles. The two latter classes of
      mutants suggest that IN can affect DNA synthesis or integration during infection
      in ways that are not appreciated from currently used assays in vitro.

PMID- 8551609
TI  - Random removal of inserts from an RNA genome: selection against single-stranded
      RNA.
AB  - We have monitored the evolution of insertions in two MS2 RNA regions of known
      secondary structure where coding pressure is negligible or absent. Base changes
      and shortening of the inserts proceed until the excessive nucleotides can be
      accommodated in the original structure. The stems of hairpins can be dramatically
      extended but the loops cannot, revealing natural selection against single
      stranded RNA. The 3' end of the MS2 A-protein gene forms a small hairpin with an
      XbaI sequence in the loop. This site was used to insert XbaI fragments of various
      sizes. Phages produced by these MS2 cDNA clones were not wild type, nor had they
      retained the full insert. Instead, every revertant phage had trimmed the insert
      in a different way to leave a four- to seven-membered loop to the now extended
      stem. Similar results were obtained with inserts in the 5' untranslated region.
      The great number of different revertants obtained from a single starting mutant
      as well as sequence inspection of the crossover points suggest that the removal
      of redundant RNA occurs randomly. The only common feature among all revertants
      appears the potential to form a hairpin with a short loop, suggesting that single
      stranded RNA negatively affects the viability of the phage. To test this
      hypothesis, we introduced XbaI fragments of 34 nucleotides that could form either
      a long stem with a small loop or a short stem with a large loop (26 nucleotides).
      The base-paired inserts were perfectly maintained for many generations, whereas
      the unpaired versions were quickly trimmed back to reduce the size of the loop.
      These data confirm that single-stranded RNA adversely affects phage fitness and
      is strongly selected against. The repair of the RNA genome that we describe here
      appears as the result of random recombination. Of the plethora of recombinants,
      only those able to adopt a base-paired structure survive. The frequency with
      which our inserts are removed seems higher than measured by others for small
      inserts in a reading frame in Q beta RNA. To account for this higher frequency,
      we suggest models in which the single-stranded nature of our inserts induces
      random recombination at the site of the insertion.

PMID- 8551610
TI  - In vivo assay of p53 function in homologous recombination between simian virus 40
      chromosomes.
AB  - To investigate a possible role of p53 in DNA exchange mechanisms, we have
      developed a model system which allows us to quantify homologous recombination
      rates in eukaryotic cells. We generated two types of simian virus 40 (SV40) whose
      genomes were mutated in such a way that upon double infection of monkey cells,
      virus particles can be released only after interchromosomal exchange of genetic
      material. This test system allowed us to determine recombination rates in the
      order of 10(-4) to 10(-6) for chromatin-associated SV40 genomes. To study the
      role of p53-T-antigen (T-Ag) complexes in this process, we designed viral test
      genomes with an additional mutation leading to a single amino acid exchange in T
      Ag (D402H) and specifically blocking T-Ag-p53 interactions. Analysis of primary
      rhesus monkey cells endogenously expressing wild-type p53 showed a decreased
      recombination rate upon loss of efficient T-Ag-p53 complex formation. However,
      cells expressing mutant p53 (LLC-MK2 cells), the introduction of mutant T-Ag did
      not affect the DNA exchange rates. Our data are interpreted to indicate an
      inhibitory role of wild-type p53 in recombination. In agreement with this
      hypothesis, p53-T-Ag complex formation alleviates the inhibitory effect of wild
      type p53.

PMID- 8551611
TI  - The block of adipocyte differentiation by a C-terminally truncated, but not by
      full-length, simian virus 40 large tumor antigen is dependent on an intact
      retinoblastoma susceptibility protein family binding domain.
AB  - Simian virus 40 (SV40) can promote cell transformation and suppress
      differentiation. It does this partly by targeting tumor suppressors such as p53
      and members of the retinoblastoma susceptibility protein (Rb) family. This work
      concentrates on mechanisms by which SV40 large tumor antigen (SVLT) suppresses
      adipocyte differentiation. We created cell lines derived from murine 3T3-L1
      preadipocytes expressing different versions of SV40 early-region sequences. SVLT
      expressing cells failed to exhibit adipocyte morphology, to induce
      glycerophosphate dehydrogenase activity, and to induce differentiation-dependent
      mRNA for adipocyte P2. SVLT alone was sufficient, in the absence of SV40 small
      tumor antigen, to inhibit differentiation. A truncated SVLT containing only the N
      terminal 121 amino acids (SVLT1-121) blocked differentiation, thus mapping at
      least one differentiation blocking function to the N-terminal region. K1 (Glu-107
      ->Lys) point mutants of SVLT, which are unable to bind to the Rb protein family
      or induce neoplastic transformation, are defective for blocking differentiation
      in the case of SVLT1-121 but retain the ability to block differentiation in the
      case of full-length SVLT. This finding demonstrates that Rb family proteins are
      important in regulating adipocyte differentiation but that other functions of
      full-length SVLT can block adipocyte differentiation independently of RB family
      binding and transformation.

PMID- 8551612
TI  - Humoral response to oligomeric human immunodeficiency virus type 1 envelope
      protein.
AB  - The humoral immune response to human immunodeficiency virus type 1 (HIV-1) is
      often studied by using monomeric or denatured envelope proteins (Env). However,
      native HIV-1 Env complexes that maintain quaternary structure elicit immune
      responses that are qualitatively distinct from those seen with monomeric or
      denatured Env. To more accurately assess the levels and types of antibodies
      elicited by HIV-1 infection, we developed an antigen capture enzyme-linked
      immunosorbent assay using a soluble, oligomeric form of HIV-1IIIB Env (gp140)
      that contains gp120 and the gp41 ectodomain. The gp140, captured by various
      monoclonal antibodies (MAbs), retained its native oligomeric structure: it bound
      CD4 and was recognized by MAbs to conformational epitopes in gp120 and gp41,
      including oligomer-specific epitopes in gp41. We compared the reactivities of
      clade B and clade E serum samples to captured Env preparations and found that
      while both reacted equally well with oligomeric gp140, clade B seras reacted more
      strongly with monomeric gp120 than did clade E samples. However, these
      differences were minimized when gp120 was captured by a V3 loop MAb, which may
      lead to increased exposure of the CD4 binding site. We also measured the ability
      of serum samples to block binding of MAbs to epitopes in gp120 and gp41. Clade B
      serum samples consistently blocked binding of oligomer-dependent MAbs to gp41
      and, to a slightly lesser extent, MAbs to the CD4 binding site in gp120. Clade E
      serum samples showed equivalent or greater blocking of oligomer-dependent gp41
      antibodies and considerably less blocking of CD4-binding-site MAbs. Finally, we
      found that < 5% of the antibodies in clade B sera bound to epitopes present only
      in monomeric gp120, 30% bound to epitopes present in both monomeric gp120 and
      oligomeric gp140, and 70% bound to epitopes present in oligomeric gp140, which
      includes gp41. Thus, captured oligomeric Env closely reflects the antigenic
      characteristics of Env protein on the surface of virions and infected cells,
      retains highly conserved epitopes that are recognized by antibodies raised
      against different clades, and makes it possible to detect a much greater fraction
      of total anti-HIV-1 Env activity in sera than does native monomeric gp120.

PMID- 8551613
TI  - Infectious RNA transcribed from an engineered full-length cDNA template of the
      genome of a pestivirus.
AB  - Infectious RNA was transcribed for the first time from a full-length cDNA
      template of the plus-strand RNA genome of a pestivirus. The genome of the C
      strain, which is a vaccine strain of classical swine fever virus, was sequenced
      and used to synthesize the template. The cDNA sequence of the C strain was found
      to be 12,311 nucleotides in length and contained one large open reading frame
      encoding a polyprotein of 3,898 amino acids. Although there were mostly only
      small differences between the sequence of the C strain and the published
      sequences of strains Alfort and Brescia, there was one notable insertion of 13
      nucleotides, TTTTCTTTTTTTT, in the 3' noncoding region of the C strain.
      Furthermore, we showed that the sequences at the 5' and 3' termini of the C
      strain are highly conserved among pestiviruses. We found that the infectivity of
      the in vitro transcripts of DNA copies pPRKflc-113 and pPRKflc-133 depended on
      the correctness of the nucleotide sequence. The in vitro transcripts of pPRKflc
      133 were infectious, whereas those of pPRKflc-113 were not. In fact, only 5 amino
      acids among the complete amino acid sequence determined this difference in
      infectivity. However, virus FLc-133, which was generated from pPRKflc-133, cannot
      be differentiated from native C-strain virus. Therefore, we exchanged the region
      encoding the antigenic N-terminal half of envelope protein E2 in pPRKflc-133 with
      the equivalent region of strain Brescia. The resulting hybrid virus, FLc-h6,
      could be differentiated from the C strain and from FLc-133 with monoclonal
      antibodies directed against envelope proteins Erns and E2 of strain Brescia and
      the C strain. To be suitable for further vaccine development, viruses generated
      from pPRKflc-133 should grow at least as well as native C-strain virus. In fact,
      we found that FLc-133, hybrid virus FLc-h6, and the C strain grew equally well.
      We concluded that pPRKflc-133 is an excellent tool for developing a classical
      swine fever marker vaccine and may prove valuable for studying the replication,
      virulence, cell and host tropism, and pathogenesis of classical swine fever
      virus.

PMID- 8551614
TI  - Mutations of basic amino acids of NCp7 of human immunodeficiency virus type 1
      affect RNA binding in vitro.
AB  - The nucleocapsid (NC) protein of human immunodeficiency virus type 1 is required
      for packaging of viral RNA and for virion assembly. It contains two clusters of
      basic amino acids, consisting of five and four amino acid residues, flanking the
      first of its two zinc fingers. These amino acid residues have been mutagenized to
      neutral ones individually, as well as in various combinations, by site-directed
      mutagenesis. Wild-type NCp7 and the mutant proteins were expressed as recombinant
      proteins in Escherichia coli, with six histidines as tags at their amino termini
      in order to allow efficient purification. The purified proteins were analyzed for
      RNA binding in vitro with human immunodeficiency virus type 1 5' leader RNA
      transcribed in vitro. Assays comprised Northwestern blots at various salt
      concentrations and filter binding tests which allowed determination of the
      dissociation constants of the various mutants. The results indicated that
      mutations of the amino acid R-7 and of R-32 and K-33 were more critical for RNA
      binding than other mutations. Mutation of the other amino acid residues reduced
      the binding affinity in proportion to the number of mutations. Mutation of seven
      of the nine basic amino acid residues reduced the binding of RNA by 50- to 90
      fold.

PMID- 8551615
TI  - Hepatitis C virus glycoprotein folding: disulfide bond formation and association
      with calnexin.
AB  - The hepatitis C virus (HCV) glycoproteins (E1 and E2) are released from the
      polyprotein by signal peptidase-mediated cleavage and interact to form a
      heterodimer. Since properly folded subunits are usually required for specific
      recognition and stable oligomer formation, the rate of stable E1E2 complex
      formation, which is low, may be limited by the rate of HCV E1 and/or E2 folding.
      In this study, the folding of the HCV E1 and E2 glycoproteins was monitored by
      observing the kinetics of intramolecular disulfide bond formation. The
      association/dissociation of E1 and E2 with calnexin was also examined, since this
      molecular chaperone appears to play a major role in quality control via retention
      of incompletely folded or misfolded proteins in the endoplasmic reticulum. Our
      results indicate that the disulfide-dependent folding of E2 occurs rapidly and
      appears to be complete upon cleavage of the precursor E2-NS2. In contrast,
      folding of E1 is slow (> 1 h), suggesting that this step may be rate limiting for
      E1E2 oligomerization. Both HCV glycoproteins associated rapidly with calnexin,
      but dissociation was slow, consistent with the slow folding and assembly of E1E2
      glycoprotein complexes. These results suggest a role for prolonged association
      with calnexin in the folding and assembly of HCV glycoprotein heterodimer
      complexes.

PMID- 8551616
TI  - Resistance of herpes simplex virus type 1 to peptidomimetic ribonucleotide
      reductase inhibitors: selection and characterization of mutant isolates.
AB  - Herpes simplex virus (HSV) encodes its own ribonucleotide reductase (RR), which
      provides the high levels of deoxynucleoside triphosphates required for viral DNA
      replication in infected cells. HSV RR is composed of two distinct subunits, R1
      and R2, whose association is required for enzymatic activity. Peptidomimetic
      inhibitors that mimic the C-terminal amino acids of R2 inhibit HSV RR by
      preventing the association of R1 and R2. These compounds are candidate antiviral
      therapeutic agents. Here we describe the in vitro selection of HSV type 1 KOS
      variants with three- to ninefold-decreased sensitivity to the RR inhibitor BILD
      733. The resistant isolates have growth properties in vitro similar to those of
      wild-type KOS but are more sensitive to acyclovir, possibly as a consequence of
      functional impairment of their RRs. A single amino acid substitution in R1 (Ala
      1091 to Ser) was associated with threefold resistance to BILD 733, whereas an
      additional substitution (Pro-1090 to Leu) was required for higher levels of
      resistance. These mutations were reintroduced into HSV type 1 KOS and shown to be
      sufficient to confer the resistance phenotype. Studies in vitro with RRs isolated
      from cells infected with these mutant viruses demonstrated that these RRs bind
      BILD 733 more weakly than the wild-type enzyme and are also functionally
      impaired, exhibiting an elevated dissociation constant (Kd) for R1-R2 subunit
      association and/or reduced activity (kcat). This work provides evidence that the
      C-terminal end of HSV R1 (residues 1090 and 1091) is involved in R2 binding
      interactions and demonstrates that resistance to subunit association inhibitors
      may be associated with compromised activity of the target enzyme.

PMID- 8551617
TI  - Vaccinia virion protein I8R has both DNA and RNA helicase activities:
      implications for vaccinia virus transcription.
AB  - A nucleic acid-dependent ATPase was purified from vaccinia virions and shown to
      have both DNA:DNA and RNA:RNA helicase activities. This is only the third
      helicase to be identified that can unwind both DNA and RNA duplexes. The DNA
      helicase activity copurified with nucleoside triphosphate phosphohydrolase II
      (NPHII), an RNA helicase encoded by gene I8R (S. Shuman, Proc. Natl. Acad. Sci.
      USA 89:10935-10939, 1992). Immunodepletion with two antisera to NPHII and
      analysis of recombinant NPHII protein (C. H. Gross and S. Shuman, J. Virol.
      69:4727-4736, 1995) confirmed that the DNA helicase activity was encoded by the
      I8R gene. The I8R DNA helicase unwound DNA in a 3'-to-5' direction only, unwound
      duplexes of 35 bp but not 45 bp, and could be stimulated to unwind longer
      duplexes by the Escherichia coli single-stranded DNA-binding protein. DNA
      helicase activity was not stimulated by salt and was sensitive to 100 mM NaCl or
      KCl. The I8R protein has amino acid similarity to human RNA helicase A and to
      nuclear DNA helicase II, a bovine DNA and RNA helicase. On the basis of the
      phenotype of I8R temperature-sensitive mutants, it was suggested that the I8R
      protein is not required for DNA replication but might aid in the extrusion of
      early mRNA from the virus core. The DNA helicase activity of the I8R protein
      allows another interpretation of the mutant phenotype, namely, that the I8R DNA
      helicase activity is required for initiation of early transcription from within
      vaccinia virions.

PMID- 8551618
TI  - Identification of protein regions involved in the interaction of human
      respiratory syncytial virus phosphoprotein and nucleoprotein: significance for
      nucleocapsid assembly and formation of cytoplasmic inclusions.
AB  - We have reported previously that the nucleoprotein (N), the phosphoprotein (P),
      and the 22-kDa protein of human respiratory syncytial virus (HRSV) are components
      of the cytoplasmic inclusion bodies observed in HEp-2-infected cells. In
      addition, coexpression of N and P was sufficient to induce the formation of N-P
      complexes detectable by either coimmunoprecipitation with anti-P antibodies or
      generation of cytoplasmic inclusions. We now report the identification of protein
      regions required for these interactions. Deletion mutant analysis of the P
      protein gene indicated that its C-terminal end was essential for interacting with
      N. This conclusion was strengthened by the finding that an anti-P monoclonal
      antibody (021/12P), reacting with a 21-residue P protein C-terminal peptide,
      apparently displaced N from N-P complexes. The same effect was observed with high
      concentrations of the C-terminal peptide. However, sequence requirements for the
      P protein C-terminal end were not absolute, and mutants with the substitution Ser
      237-->Ala or Ser-237-->Thr were as efficient as the wild type in interacting with
      N. In addition, P and N proteins from strains of different HRSV antigenic groups,
      with sequence differences in the P protein C-terminal end, were able to
      coimmunoprecipitate and formed cytoplasmic inclusions. Deletion mutant analysis
      of the N gene indicated that large segments of this polypeptide were required for
      interacting with P. The relevance of these interactions for HRSV is discussed in
      comparison with those of analogous proteins from related viruses.

PMID- 8551619
TI  - The two biological activities of human immunodeficiency virus type 1 Vpu protein
      involve two separable structural domains.
AB  - The human immunodeficiency virus type 1 (HIV-1) Vpu protein is an integral
      membrane phosphoprotein that induces CD4 degradation in the endoplasmic reticulum
      and enhances virus release from the cell surface. CD4 degradation is specific,
      requires phosphorylation of Vpu, and involves the interaction between Vpu and the
      CD4 cytoplasmic domain. In contrast, regulation of virus release is less specific
      and not restricted to HIV-1 and may be mechanistically-distinct from CD4
      degradation. We show here that a mutant of Vpu, Vpu35, lacking most of its
      cytoplasmic domain has residual biological activity for virus release but is
      unable to induce CD4 degradation. This finding suggests that the N terminus of
      Vpu encoding the transmembrane (TM) anchor represents an active domain important
      for the regulation of virus release but not CD4 degradation. To better define the
      functions of Vpu's TM anchor and cytoplasmic domain, we designed a mutant, VpuRD,
      containing a scrambled TM sequence with a conserved amino acid composition and
      alpha-helical structure. The resulting protein was integrated normally into
      membranes, was able to form homo-oligomers, and exhibited expression levels,
      protein stability, and subcellular localization similar to those of wild-type
      Vpu. Moreover, VpuRD was capable of binding to CD4 and to induce CD4 degradation
      with wild-type efficiency, confirming proper membrane topology and indicating
      that the alteration of the Vpu TM domain did not interfere with this function of
      Vpu. However, VpuRD was unable to enhance the release of virus particles from
      infected or transfected cells, and virus encoding VpuRD had replication
      characteristics in T cells indistinguishable from those of a Vpu-deficient HIV-1
      isolate. Mutation of the phosphorylation sites in VpuRD resulted in a protein
      which was unable to perform either function of Vpu. The results of our
      experiments suggest that the two biological activities of Vpu operate via two
      distinct molecular mechanisms and involve two different structural domains of the
      Vpu protein.

PMID- 8551620
TI  - The envelope glycoprotein of human immunodeficiency virus type 2 enhances viral
      particle release: a Vpu-like factor?
AB  - The Vpu protein is a human immunodeficiency virus type 1 (HIV-1)-specific
      accessory protein that is required for the efficient release of viral particles
      from infected cells. Even though HIV-2 does not encode Vpu, we found that this
      virus is nevertheless capable of efficiently releasing virus particles. In fact,
      the rate of virus release from HeLa cells transfected with a full-length
      molecular clone of HIV-2, ROD10, was comparable to that observed for the vpu+ HIV
      1 NL4-3 isolate and was not further enhanced by expression of Vpu in trans.
      However, consistent with previous observations showing that HIV-2 particle
      release is Vpu responsive in the context of HIV-1/HIV-2 chimeric constructs;
      exchanging the gag-pol region of NL4-3 with the corresponding region from pROD10
      rendered the resulting chimeric virus Vpu responsive. Our finding that the
      responsiveness of HIV-2 particle release to Vpu is context dependent suggested
      the presence of a Vpu-like factor(s) encoded by HIV-2. Using chimeric proviruses
      encoding HIV-2 gag and pol in the context of the HIV-1 provirus that were
      coexpressed with subgenomic HIV-2 constructs, we found that the HIV-2 envelope
      glycoprotein had the ability to enhance HIV-2 particle release with an efficiency
      comparable to that of the HIV-1 Vpu protein. Conversely, inactivation of the HIV
      2 env gene in the original ROD10 clone resulted in a decrease in the rate of
      viral particle release to a level that was comparable to that of Vpu-deficient
      HIV-1 isolates. Providing the wild-type envelope in trans rescued the particle
      release defect of the ROD10 envelope mutant. Thus, unlike HIV-1, which encodes
      two separate proteins to regulate virus release or to mediate viral entry, the
      HIV-2 Env protein has evolved to perform both functions.

PMID- 8551621
TI  - Genetic basis for resistance to polytropic murine leukemia viruses in the wild
      mouse species Mus castaneus.
AB  - Cultured cells derived from the wild mouse species Mus castaneus were found to be
      uniquely resistant to exogenous infection by polytropic mink cell focus-forming
      (MCF) murine leukemia viruses (MuLVs). This MCF MuLV resistance is inherited as a
      genetically recessive trait in the progeny of F1 crosses between M. castaneus and
      MCF MuLV-susceptible laboratory mice. Examination of the progeny of backcrosses
      demonstrated that susceptibility is inherited as a single gene which maps to
      chromosome 1. The map location of this gene places it at or near the locus Rmc1,
      the gene encoding the receptor for MCF/xenotropic MuLVs, suggesting that
      resistance is mediated by the M. castaneus allele of this receptor.

PMID- 8551622
TI  - Efficient transactivation of the minute virus of mice P38 promoter requires
      upstream binding of NS1.
AB  - The P38 promoter of the autonomous parvovirus minute virus of mice is strongly
      transactivated by the nonstructural protein NS1, a sequence-specific DNA-binding
      protein. In the context of the complete viral genome, the only unique cis-acting
      signals required for P38 transactivation by NS1 are the proximal Sp1 site and the
      TATA element. In the absence of additional upstream sequences, a dependence upon
      the NS1 binding site within the transactivation response region is observed.
      Addition of synthetic NS1 binding sites to transactivation response region
      deletion mutants can restore the ability of NS1 to transactivate P38, and NS1
      transactivation has been directly correlated to its ability to bind upstream of
      the P38 promoter.

PMID- 8551623
TI  - Analysis of the T-cell receptor repertoire of human T-cell leukemia virus type 1
      (HTLV-1) Tax-specific CD8+ cytotoxic T lymphocytes from patients with HTLV-1
      associated disease: evidence for oligoclonal expansion.
AB  - Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP) is a chronic, progressive neurological disease
      characterized by marked degeneration of the spinal cord and the presence of
      antibodies against HTLV-1. Patients with HAM/TSP, but not asymptomatic carriers,
      show very high precursor frequencies of HTLV-1-specific CD8+ T cells in
      peripheral blood and cerebrospinal fluid, suggestive of a role of these T cells
      in the pathogenesis of the disease. In HLA-A2+ HAM/TSP patients, HTLV-1-specific
      T cells were demonstrated to be directed predominantly against one HTLV-1
      epitope, namely, Tax11-19. In the present study, we analyzed HLA-A2-restricted
      HTLV-1 Tax11-19-specific cytotoxic T cells from three patients with HAM/TSP. An
      analysis of the T-cell receptor (TCR) repertoire of these cells revealed an
      absence of restricted variable (V) region usage. Different combinations of TCR V
      alpha and V beta genes were utilized between, but also within, the individual
      patients for the recognition of Tax11-19. Sequence analysis of the TCR showed
      evidence for an oligoclonal expansion of few founder T cells in each patient.
      Apparent structural motifs were identified for the CDR3 regions of the TCR beta
      chains. One T-cell clone could be detected within the same patient over a period
      of 3 years. We suggest that these in vivo clonally expanded T cells might play a
      role in the pathogenesis of HAM/TSP and provide information on HTLV-1-specific
      TCR which may elucidate the nature of the T cells that infiltrate the central
      nervous system in HAM/TSP patients.

PMID- 8551625
TI  - Human adenovirus type 9 E4 open reading frame 1 encodes a cytoplasmic
      transforming protein capable of increasing the oncogenicity of CREF cells.
AB  - The induction of estrogen-dependent rat mammary tumors by human adenovirus type 9
      (Ad9) requires the Ad9 E4 open reading frame 1 (9ORF1) protein, which alone can
      transform that rat embryo fibroblast cell line CREF in vitro. In the present
      study, independent pools of both 9ORF1-expressing and control CREF cells were
      generated by selection with G418 and compared with respect to transformed
      properties. Indirect immunofluorescence analyses revealed that more than 99% of
      the cells that made up the 9ORF1-transfected pools expressed 9ORF1 protein and,
      together with confocal laser scanning microscopy, indicated that this E4 protein
      was located predominantly within the cytoplasm of cells. With regard to
      transformation, cells of the 9ORF1-expressing pools differed from those of
      control pools by forming foci, displaying morphological alterations, growing more
      efficiently in soft agar, and reaching higher saturation densities. Following
      injection into immunocompetent syngeneic rats, the 9ORF1-expressing pool cells
      exhibited greatly enhanced oncogenicity compared with control pool cells. These
      results show that 9ORF1 protein (i) localizes predominantly within the cytoplasm,
      (ii) confers multiple general transformed characteristics to CREF cells in vitro,
      and (iii) increases the tumorigenic properties of these cells in vivo.

PMID- 8551624
TI  - The relationship between capsid protein (VP2) sequence and pathogenicity of
      Aleutian mink disease parvovirus (ADV): a possible role for raccoons in the
      transmission of ADV infections.
AB  - Aleutian mink disease parvovirus (ADV) DNA was identified by PCR in samples from
      mink and raccoons on commercial ranches during an outbreak of Aleutian disease
      (AD). Comparison of DNA sequences of the hypervariable portion of VP2, the major
      capsid protein of ADV, indicated that both mink and raccoons were infected by a
      new isolate of ADV, designated ADV-TR. Because the capsid proteins of other
      parvoviruses play a prominent role in the determination of viral pathogenicity
      and host range, we decided to examine the relationship between the capsid protein
      sequences and pathogenicity of ADV. Comparison of the ADV-TR hypervariable region
      sequence with sequences of other isolates of ADV revealed that ADV-TR was 94 to
      100% related to the nonpathogenic type 1 ADV-G at both the DNA and amino acid
      levels but less than 90% related to other pathogenic ADVs like the type 2 ADV
      Utah, the type 3 ADV-ZK8, or ADV-Pullman. This finding indicated that a virus
      with a type 1 hypervariable region could be pathogenic. To perform a more
      comprehensive analysis, the complete VP2 sequence of ADV-TR was obtained and
      compared with that of the 647-amino-acid VP2 of ADV-G and the corresponding VP2
      sequences of the pathogenic ADV-Utah, ADV-Pullman, and ADV-ZK8. Although the
      hypervariable region amino acid sequence of ADV-TR was identical to that of ADV
      G, there were 12 amino acid differences between ADV-G and ADV-TR. Each of these
      differences was at a position where other pathogenic isolates also differed from
      ADV-G. Thus, although ADV-TR had the hypervariable sequence of the nonpathogenic
      type 1 ADV-G, the remainder of the VP2 sequence resembled sequences of other
      pathogenic ADVs. Under experimental conditions, ADV-TR and ADV-Utah were highly
      pathogenic and induced typical AD in trios of both Aleutian and non-Aleutian
      mink, whereas ADV-Pullman was pathogenic only for Aleutian mink and ADV-G was
      noninfectious. Trios of raccoons experimentally inoculated with ADV-TR and ADV
      Utah all became infected with ADV, but only a single ADV-Pullman-inoculated
      raccoon showed evidence of infection. Furthermore, none of the ADV isolates
      induced pathological findings of AD in raccoons. Finally, when a preparation of
      ADV-TR prepared from infected raccoon lymph nodes was inoculated into mink and
      raccoons, typical AD was induced in Aleutian and non-Aleutian mink, but raccoons
      failed to show serological or pathological evidence of infection. These results
      indicated that raccoons can become infected with ADV and may have a role in the
      transmission of virus to mink but that raccoon-to-raccoon transmission of ADV is
      unlikely.

PMID- 8551626
TI  - The cytoplasmic tail of influenza A virus neuraminidase (NA) affects NA
      incorporation into virions, virion morphology, and virulence in mice but is not
      essential for virus replication.
AB  - In this study, we investigated the role of the conserved neuraminidase (NA)
      cytoplasmic tail residues in influenza virus replication. Mutants of influenza A
      virus (A/WSN/33 [H1N1]) with deletions of the NA cytoplasmic tail region were
      generated by reverse genetics. The resulting viruses, designated NOTAIL, contain
      only the initiating methionine of the conserved six amino-terminal residues. The
      mutant viruses grew much less readily and produced smaller plaques than did the
      wild-type virus. Despite similar levels of NA cell surface expression by the
      NOTAIL mutants and wild-type virus, incorporation of mutant NA molecules into
      virions was decreased by 86%. This reduction resulted in less NA activity per
      virion, leading to the formation of large aggregates of progeny mutant virions on
      the surface of infected cells. A NOTAIL virus containing an additional mutation
      (Ser-12 to Pro) in the transmembrane domain incorporated three times more NA
      molecules into virions than did the NOTAIL parent but approximately half of the
      amount incorporated by the wild-type virus. However, aggregation of the progeny
      virions still occurred at the cell surface. All NOTAIL viruses were attenuated in
      mice. We conclude that the cytoplasmic tail of NA is not absolutely essential for
      virus replication but exerts important effects on the incorporation of NA into
      virions and thus on the aggregation and virulence of progeny virus. In addition,
      the relative abundance of long filamentous particles formed by the NOTAIL
      mutants, compared with the largely spherical wild-type particles, indicates a
      role for the NA cytoplasmic tail in virion morphogenesis.

PMID- 8551627
TI  - trans-acting proteins involved in RNA encapsidation and viral assembly in human
      immunodeficiency virus type 1.
AB  - The human immunodeficiency virus type 1 gag gene product Pr55gag self-assembles
      when expressed on its own in a variety of eukaryotic systems. Assembly in T
      lymphocytes has not previously been studied, nor is it clear whether Pr55gag
      particles can package genomic RNA or if the Gag-Pol polyprotein is required. We
      have used a series of constructs that express Gag or Gag-Pol proteins with or
      without the viral protease in transient transfections in COS-1 cells and also
      expressed stably in CD4+ T cells to study this. Deletion of the p6 domain at the
      C terminus of protease-negative Pr55gag did not abolish particle release, while
      truncation of the nucleocapsid protein reduced it significantly, particularly in
      lymphocytes. Gag-Pol polyprotein was released from T cells in the absence of
      Pr55gag but did not encapsidate RNA. Pr55gag encapsidated human immunodeficiency
      virus type 1 RNA whether expressed in a protease-positive or protease-negative
      context. p6 was dispensable for RNA encapsidation. Marked differences in the
      level of RNA export were noted between the different cell lines.

PMID- 8551628
TI  - An array of murine leukemia virus-related elements is transmitted and expressed
      in a primate recipient of retroviral gene transfer.
AB  - Direct RNA-PCR analyses of T-cell lymphomas that developed in rhesus macaques
      during a gene transfer experiment revealed the presence of several different
      recombinant murine leukemia viruses (MuLV). Most prominent was the expected MuLV
      recombinant, designated MoLTRAmphoenv in which the amphotropic env of the helper
      packaging virus was joined to the long terminal repeat (LTR) of the Moloney MuLV
      derived vector. This retrovirus does not exist in nature. An additional copy of
      the core enhancer acquired from the vector LTR may have augmented the replicative
      properties of MoLTRAmphoenv MuLV in several different rhesus cell types compared
      with the prototype amphotropic MuLV4070A. Unexpectedly, at least two types of
      mink cell focus-forming MuLV elements, arising from endogenous retroviral
      sequences expressed in the murine packaging cell line, were also transmitted and
      highly expressed in one of the macaques. Furthermore, murine virus-like VL-30
      sequences were detected in the rhesus lymphomas, but these were not transcribed
      into RNA. The unanticipated presence of an array of MuLV-related structures in a
      primate gene transfer recipient demands ever-vigilant scrutiny for the existence
      of transmissible retroviral elements and replication-competent viruses possessing
      altered tropic or growth properties in packaging cells producing retroviral
      vectors.

PMID- 8551629
TI  - Neutrophil-mediated suppression of virus replication after herpes simplex virus
      type 1 infection of the murine cornea.
AB  - Herpes simplex virus type 1 (HSV-1) infection of the murine cornea induces the
      rapid infiltration of neutrophils. We investigated whether these cells could
      influence virus replication. BALB/c mice treated with monoclonal antibody (MAb)
      RB6-8C5 experienced a profound depletion of neutrophils in the bloodstream,
      spleen, and cornea. In these animals, virus titers in the eye were significantly
      higher than those in the immunoglobulin G-treated controls at 3 days
      postinfection. By day 9, virus was no longer detectable in the controls, whereas
      titers of 10(3) to 10(6) PFU were still present in the neutrophil-depleted hosts.
      Furthermore, virus spread more readily to the skin and brains of MAb RB6-8C5
      treated animals, rendering them significantly more susceptible to HSV-1-induced
      blepharitis and encephalitis. Only 25% of the treated animals survived, whereas
      all of the controls lived. Although MAb RB6-8C5 treatment did not alter the CD4+
      T-cell, B-cell, natural killer cell, or macrophage populations, the CD8+ T-cell
      population was partially reduced. Therefore, the experiments were repeated in
      severe combined immunodeficiency mice, which lack CD8+ T cells. Again virus
      growth was found to be significantly elevated in the eyes, trigeminal ganglia,
      and brains of the MAb RB6-8C5-treated hosts. These results strongly indicate that
      in both immunocompetent and immunodeficient mice, neutrophils play a significant
      role in helping to control the replication and spread of HSV-1 after corneal
      infection.

PMID- 8551630
TI  - Overexpression of the vaccinia virus A38L integral membrane protein promotes Ca2+
      influx into infected cells.
AB  - The vaccinia virus Western Reserve A38L protein is a hydrophobic integral
      membrane glycoprotein with amino acid similarity to mammalian integrin-associated
      protein. The protein has an N-terminal immunoglobulin superfamily domain,
      followed by five membrane-spanning domains and a short cytoplasmic tail. Deletion
      of the protein reduces virus plaque size but does not affect virus virulence (J.
      E. Parkinson, C. M. Sanderson, and G. L. Smith, Virology, in press). In this
      study, we have used a recombinant vaccinia virus in which the A38L gene may be
      inducibly overexpressed by addition of isopropyl-beta-D-thiogalactopyranoside
      (IPTG), to demonstrate that overexpression of the vaccinia virus A38L gene
      produces drastic changes in the morphology, permeability, and adhesion of
      infected cells. In particular, A38L overexpression caused swelling of cells,
      marginalization of nuclear chromatin, and vacuolization of the endoplasmic
      reticulum, features characteristic of cell necrosis. By 18 h postinfection, cells
      become permeable and lytic as defined by the free entry of propidium iodide and
      loss of the cytoplasmic enzyme lactate dehydrogenase. Chelation of extracellular
      Ca2+ 22 h postinfection inhibited further release of lactate dehydrogenase,
      showing that Ca2+ influx was required for A38L-induced lysis. Direct measurement
      of 45Ca2+ influx showed that the rate of Ca2+ uptake was directly related to the
      period of A38L induction. The A38L protein, therefore, promotes the formation of
      pores within the plasma membrane of cells, and these pores facilitate Ca2+ entry
      and induce necrosis. Addition of rifampin inhibited virus assembly but not the
      ability of A38L to induce necrosis, indicating that pore formation is independent
      of viral morphogenesis. Finally, overexpression of the A38L protein resulted in a
      reduced plaque size and a threefold decrease in production of infective particles
      in vitro. The A38L protein represents the first example of a virus protein which
      directly or indirectly promotes the influx of extracellular Ca2+.

PMID- 8551631
TI  - Inhibition of bunyaviruses, phleboviruses, and hantaviruses by human MxA protein.
AB  - Viruses of the Bunyaviridae family cause a variety of diseases ranging from
      uncomplicated fever to potentially lethal encephalitis and hemorrhagic fever.
      Little is known about the factors determining pathogenicity in the vertebrate
      host. Interferons have been reported to be inhibitory, but their mode of action
      against members of the Bunyaviridae has not yet been elucidated. The interferon
      induced MxA protein encoded on human chromosome 21 is a large GTPase with
      antiviral activity against distinct negative-strand RNA viruses, notably
      influenza viruses. Here we show that MxA inhibits representative members of the
      Bunyaviridae family by interacting with an early step of virus replication. When
      constitutively expressed in stably transfected Vero cells, MxA prevented the
      accumulation of viral transcripts and proteins of Hantaan virus (genus
      Hantavirus). Other members of the family such as La Crosse virus (genus
      Bunyavirus) and Rift Valley fever virus and sandfly fever virus (both genus
      Phlebovirus) were likewise inhibited, and virus titers were reduced up to 10(4)
      fold. Our data indicate that humans have evolved a mechanism of controlling these
      viruses irrespective of differences in viral coding strategies.

PMID- 8551632
TI  - PCR-in situ hybridization detection of human T-cell lymphotropic virus type 1
      (HTLV-1) tax proviral DNA in peripheral blood lymphocytes of patients with HTLV-1
      associated neurologic disease.
AB  - PCR-in situ hybridization (PCR-ISH) was developed and utilized to determine the
      distribution of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA
      in peripheral blood lymphocytes (PBL) from patients with HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). PCR-ISH of HTLV-1 tax DNA in
      PBL from patients with HAM/TSP revealed that 1 in 5,000 to 1 in 10,000 PBL
      contained virus. PCR-ISH was sensitive, because a positive signal was
      consistently demonstrated from the HTLV-1-infected cell lines HUT-102 (which
      contains four to six copies of HTLV-1 proviral DNA per cell) and MT-1 (which
      contains one to three copies of HTLV-1 proviral DNA per cell). Also,
      intracellular amplification by PCR-ISH significantly increased sensitivity
      compared with conventional ISH and was shown to be specific for HTLV-1 tax DNA.
      These results are in contrast to solution-phase PCR amplification in which
      greater than 1% of cells were estimated to be infected. The discordance between
      these results is discussed and may indicate that more than one copy of HTLV-1 tax
      proviral DNA is present in an individual PBL.

PMID- 8551633
TI  - Vaccinia virions lacking core protein VP8 are deficient in early transcription.
AB  - When synthesis of the 25-kDa vaccinia virus core protein VP8 is repressed, mature
      virus particles of normal appearance are produced to approximately 80% of wild
      type levels but these particles are over 100-fold less infectious than wild-type
      particles (D. Wilcock and G. L. Smith, Virology 202:294-304, 1994). Here we show
      that virions which lack VP8 can bind to and enter cells but the levels of steady
      state RNA are greatly reduced in comparison with those for wild-type infections.
      In vitro assays using permeabilized virions demonstrated that VP8-deficient
      virions had drastically reduced rates of transcription (RNA synthesis was
      decreased by 80 to 96%) and that the extrusion of RNA transcripts from these
      virions was also decreased. Low concentrations of sodium deoxycholate extracted
      proteins more efficiently from VP8-deficient virions than from wild-type virions.
      The increased fragility of VP8-deficient virions and their slower RNA extrusion
      rates suggest that VP8 may be required for the correct formation of the core.
      Virions which lack VP8 were shown to contain a full complement of transcription
      enzymes, and soluble extracts from these virions were active in transcription
      assays using either single-stranded M13 DNA or exogenous plasmid template
      containing a vaccinia virus early promoter. Thus, the defect in transcription is
      due not to a lack of specific transcriptional enzymes within virions but rather
      to the inability of these enzymes to efficiently transcribe the DNA genome
      packaged within VP8-deficient virions. These results suggest that VP8 is required
      for the correct packaging of the viral DNA genome and/or for the efficient
      transcription of packaged virion DNA, which has a higher degree of structural
      complexity than plasmid templates. Possible roles for VP8 in these processes are
      discussed.

PMID- 8551634
TI  - The human immunodeficiency virus type 1 5' packaging signal structure affects
      translation but does not function as an internal ribosome entry site structure.
AB  - The role of the RNA secondary structure in the 5' packaging signal region of
      human immunodeficiency virus type 1 (HIV-1) in initiating translation of gag mRNA
      has been investigated both in vitro and in the presence of cellular cofactors in
      vivo. Heat denaturation of the structure and mutagenic deletion both lead to an
      increase in levels of translated products, indicating that the structure is a
      significant inhibitor of translation. The proximity of the gag AUG to the
      packaging signal structure suggested that it might function as an internal
      ribosome entry site. However, in both a cell-free system and eukaryotic cells,
      translation will initiate at a novel upstream initiation codon introduced within
      the 5' noncoding region. This codon is utilized exclusively, resulting in gag
      protein products with an extra 11 amino acids at the amino terminus, which, when
      expressed in T lymphocytes, are confined intracellularly, probably because of the
      lack of an N-terminal glycine myristoylation signal. Deletion of the secondary
      structure abolishes gag production even in the presence of tat and rev in trans.
      Using dicistronic constructs containing the HIV-1 5' leader cloned between two
      heterologous open reading frames, we were unable to detect any significant
      expression of the second open reading frame that would have been supportive of an
      internal ribosome entry site mechanism. Using mutant proviruses either lacking
      the entire packaging signal structure region or containing the introduced
      upstream initiation codon in long-term replication studies, we were unable to
      detect reverse transcriptase activity in culture supernatants. The 5' packaging
      signal structure of HIV-1 does not serve as an internal ribosome entry site. The
      translation of gag is consistent with ribosomal scanning. However, the packaging
      signal structure causes significant translational inhibition.

PMID- 8551635
TI  - Events in the endoplasmic reticulum abrogate the temperature sensitivity of
      Sindbis virus mutant ts23.
AB  - Temperature-sensitive mutations in proteins produced at or heated to a
      nonpermissive temperature render the proteins defective in some aspect of their
      maturation into functional entities. The characterization of temperature
      sensitive mutations in model proteins, such as virus membrane proteins, has
      allowed the elucidation of critical events in the maturation of virus membranes
      as well as in the intracellular folding, processing, and transport of membrane
      proteins in general. We have used a transport-defective, temperature-sensitive
      mutant of Sindbis virus, ts23, which has two amino acid changes in the envelope
      protein E1, to further examine requirements placed upon the glycoproteins for
      their export to the plasma membrane. Pulse-chase experiments in which we utilized
      the transport inhibitors monensin and brefeldin A allowed us to synthesize and
      assemble the glycoproteins of ts23 into export-competent heterodimers at the
      permissive temperature while concurrently blocking their export to the cell
      surface. After removal of the inhibitors and a shift to the nonpermissive
      temperature, we assayed for protein transport, cell-cell fusion, and infectious
      particle production. Taken together, the data show that the irreversible loss of
      the temperature-sensitive phenotype of ts23 can be correlated with the folding of
      E1 and the formation of export-competent PE2-E1 heterodimers in the endoplasmic
      reticulum. Furthermore, we have found that E1 pairs with PE2 to form the
      heterodimer prior to the completion of E1 folding.

PMID- 8551636
TI  - Immunization with viruslike particles induces long-term protection of rabbits
      against challenge with cottontail rabbit papillomavirus.
AB  - Rabbits were immunized with recombinant baculovirus-produced virus-like particles
      (VLPs) of cottontail rabbit papillomavirus (CRPV) to determine whether these
      antigens could induce long-term protection against experimental challenge with
      CRPV. Infectious CRPV and human papillomavirus type 11 L1 VLPs were used as
      positive and negative control immunogens, respectively. Three groups of immunized
      animals were challenged with 10-fold serial dilutions of infectious CRPV at 2
      weeks, 6 months, and 12 months after immunizations. Antibody titers in serum
      reached 1:10,000 immediately after the final booster immunization and then
      decayed to 1:150 at 6 months and 1:100 at 12 months in unchallenged rabbits.
      Serum neutralization titers followed similar kinetics. Papillomas grew on control
      immunized rabbits at sites challenged with 10(-1) (100% of sites), 10(-2) (96% of
      sites), 10(-3) (63% of sites), and 10(-4) (13% of sites) dilutions of virus. At 2
      weeks after CRPV L1 VLP immunizations, the rabbits were completely protected
      against virus challenge. At both 6 and 12 months after CRPV L1 VLP immunizations,
      strong protection was also observed. In the last two groups, three of seven
      rabbits were completely protected and only 4 of 14 or 29% of sites challenged
      with 10(-1 dilution of virus grew papillomas. Papillomas growing at these four
      sites were also reduced in size (3.5 +/- 0.7 mm) at 50 days postchallenge
      compared with sites challenged with 10(-1) dilution on control-immunized rabbits
      (13.2 +/- 4.2 mm). The results demonstrate that strong and long-lasting
      protection against experimental challenge with papillomaviruses can be achieved
      with VLP immunogens.

PMID- 8551637
TI  - Construction of a type 1 human immunodeficiency virus that maintains a primer
      binding site complementary to tRNA(His).
AB  - The initiation of human immunodeficiency virus type 1 reverse transcription
      occurs by extension of a tRNA(Lys3) primer bound near the 5' end of the viral RNA
      genome which is designated the primer binding site (PBS). Sequences within the
      viral genome upstream of the PBS which are complementary to the anticodon loop
      (USUU) and the T psi C loop and arm (AGGGTm psi) of tRNA(Lys3) are postulated to
      play a role in maintaining the selective use of tRNA(Lys3) in reverse
      transcription. To investigate this possibility, proviral genomes which contain a
      PBS complementary to the 3'-terminal 18 nucleotides of tRNA(His) [pHXB2(His)] as
      well as sequences upstream of this PBS which are complementary to either the
      anticodon loop [CCACAA; pHXB2(His-AC)] or T psi C loop [GACCGAGG; pHXB2(His-T psi
      C)] of tRNA(His) were constructed. Infectious virus was recovered upon
      transfection into COS-1 cells of pHXB2(His), pHXB2(His-AC), or pHXB2(His-T psi
      C). The appearance of infectious virus after cocultivation with SupT1 cells was
      delayed for the proviruses containing a PBS complementary to tRNA(His) compared
      with that obtained by transfection of the wild-type provirus [pHXB2(WT)].
      However, by several passages in SupT1 cells, the mutant viruses demonstrated
      replication kinetics similar to those of the wild-type virus. A DNA sequence
      analysis of the PBS region from integrated proviruses revealed that by day 15 of
      culture, the PBS of viruses derived from pHXB2(His) and pHXB2(His-T psi C)
      reverted back to the wild-type PBS complementary to tRNA(Lys3). In contrast,
      viruses derived from pHXB2(His-AC) maintained a PBS complementary to tRNA(His)
      for over 4 months in culture encompassing 12 serial passages. This study, then,
      is the first report of a stable human immunodeficiency virus type 1 which
      utilizes an alternative tRNA primer and suggests that interactions between the
      primer tRNA anticodon loop and viral sequences upstream of the PBS contribute to
      the specificity of the tRNA primer used in reverse transcription.

PMID- 8551638
TI  - The spontaneous reactivation function of the herpes simplex virus type 1 LAT gene
      resides completely within the first 1.5 kilobases of the 8.3-kilobase primary
      transcript.
AB  - The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) gene
      is essential for efficient spontaneous reactivation of HSV-1 from latency. We
      report here that although the LAT gene is 8.3 kb in length, the first 1.5 kb of
      the LAT gene alone is sufficient for wild-type levels of spontaneous
      reactivation. We began with a LAT deletion mutant of HSV-1 strain McKrae in which
      the LAT promoter and the first 1.6 kb of the 5' end of the LAT gene had been
      deleted from both copies of LAT (one in each viral long repeat). As we previously
      reported, this mutant (dLAT2903) was significantly impaired for spontaneous
      reactivation (G. C. Perng, E. C. Dunkel, P. A. Geary, S. M. Slanina, H. Ghiasi,
      R. Kaiwar, A. B. Nesburn, and S. L. Wechsler, J. Virol. 68:8045-8055, 1994). We
      then inserted the LAT promoter and the first 1.5 kb of the LAT gene into a
      location in the unique long region of dLAT2903 far removed from the normal
      location of LAT in the long repeats. This resulted in a virus (LAT15a) whose
      capacity for transcribing LAT RNA was limited to the first 1.5 kb of the 8.3-kb
      LAT primary transcript. Rabbits were ocularly infected with this mutant, and
      spontaneous reactivation was measured in comparison to those of the original LAT
      negative mutant and its marker-rescued (wild-type) virus, dLAT2903R. LAT15a had
      an in vivo spontaneous reactivation rate of 12%, compared with a rate of 11% for
      the marker-rescued virus and 0% for the LAT-negative virus. Southern analysis
      confirmed that the spontaneously reactivated LAT15a virus retained the original
      deletions in both copies of LAT and the 1.5-kb LAT insertion in the unique long
      region. Thus, insertion of the first 1.5 kb of LAT (and its promoter) at a site
      distant from the normal LAT location appeared to completely restore in vivo
      spontaneous reactivation to wild-type levels, despite the remaining inability of
      the original LAT genes to transcribe any LAT RNA. The function of LAT involved in
      efficient spontaneous reactivation therefore appeared to map completely within
      the first 1.5 kb of the LAT gene.

PMID- 8551639
TI  - Recovery and characterization of a replicase complex in rotavirus-infected cells
      by using a monoclonal antibody against NSP2.
AB  - Replication of the rotavirus genome involves two steps: (i) transcription and
      extrusion of transcripts and (ii) minus-strand RNA synthesis in viral complexes
      containing plus-strand RNA. In this study, we showed evidence for the importance
      of the viral nonstructural protein of rotavirus, NSP2, in the replication of
      viral RNAs. RNA-binding properties of NSP2 were tested by UV cross-linking in
      vivo (in rotavirus-infected MA104 cells and recombinant baculovirus-expressing
      NSP2-infected Sf9 cells). In rotavirus-infected cells, NSP2 is bound to the 11
      double-stranded RNA genomic segments of rotavirus. Quantitative analysis (using
      hydrolysis by RNase A) is consistent with NSP2 being directly bound to partially
      replicated viral RNA. Using various monoclonal antibodies and specific antisera
      against the structural (VP1, VP2, and VP6) and nonstructural (NSP1, NSP2, NSP3,
      and NSP5) proteins, we developed a solid-phase assay for the viral replicase. In
      this test, we recovered a viral RNA-protein complex with replicase activity only
      with a monoclonal antibody directed against NSP2. Our results indicated that
      these viral complexes contain the structural proteins VP1, VP2, and VP6 and the
      nonstructural protein NSP2. Our results show that NSP2 is closely associated in
      vivo with the viral replicase.

PMID- 8551640
TI  - Identification of an essential region for internal initiation of translation in
      the aphthovirus internal ribosome entry site and implications for viral
      evolution.
AB  - Translation of aphthovirus RNA is initiated at an internal ribosome entry site
      (IRES) element, preceding the first functional AUG initiation codon. The effect
      of mutations at the base of domain 3 of the aphthovirus IRES on translation
      activity has been analyzed by site-directed mutagenesis and expression of
      bicistronic RNAs in transfected cells. The results have shown that the enhanced
      IRES activity associated with a single pyrimidine transition fixed in a
      persistent aphthovirus variant (E. Martinez-Salas, J. C. Saiz, M. Davila, G. J.
      Belsham, and E. Domingo, J. Virol. 67:3748-3755, 1993) is base specific.
      Mutations predicted to destabilize the base of domain 3 were detrimental to IRES
      function, but subsequent restoration of the RNA structure gave rise to fully
      competent IRES. In contrast, single or multiple mutations that did not affect
      predicted helical structures modified the relative efficiency of translation by
      at most 10-fold, suggesting that primary sequence also plays a role in IRES
      activity. A correlation between the energy of stabilization of the IRES structure
      and the efficiency of translation has been noted. None of the 15 mutations
      studied reached a level of initiation of translation comparable to that of the
      IRES from the persistent variant. The results indicate a critical participation
      of the base of domain 3 in the activity of the aphthovirus IRES, with a strong
      effect of secondary or higher-order structures and minor effects of primary
      structure.

PMID- 8551642
TI  - Catch-up growth in children with chronic renal failure treated with long-term
      enteral nutrition.
AB  - Growth retardation commonly complicates chronic renal failure in children.
      Although the etiology of this growth impairment is multifactorial, inadequate
      nutrition is considered an important cause in infants and young children. An
      "aggressive" nutritional approach has been repeatedly suggested in children with
      early onset chronic renal failure and poor feeding habits, but the possibility of
      inducing catch-up growth by energy supplementation is still controversial. The
      nutritional effects of a long-term, home-based enteral feeding program were
      studied in two infants and three children with moderate to severe chronic renal
      failure and impaired growth associated with persistent anorexia. In all patients,
      renal failure had developed during the first year of life due to congenital
      diseases. Enteral feeding was performed at home, during the night, through a
      silicone rubber nasogastric tube. The treatment lasted for 1 year. The energy
      intake ranged between 101% and 116% of the recommended dietary allowance (RDA),
      and the protein intake between 96% and 113% of the RDA in all patients but one,
      in whom proteins were restricted to 75% of the RDA. All children showed a
      substantial improvement in deviation score for both weight (mean increase +1.76),
      height (mean increase +1.52) and in the general metabolic condition, irrespective
      of age, severity of osteodystrophy, or degree of renal failure. The treatment was
      well tolerated and, apart from a few episodes of vomiting, no complications arose
      during the treatment. Tube feeding may be an effective therapeutic option for
      overcoming malnutrition when chronic renal failure is associated with persistent
      anorexia. In infants and young children, growth retardation can be opposed and
      catch-up growth obtained.

PMID- 8551641
TI  - Alteration of cell cycle kinase complexes in human papillomavirus E6- and E7
      expressing fibroblasts precedes neoplastic transformation.
AB  - Expression of viral oncoproteins results in the loss of cell cycle checkpoint
      control and the accumulation of chromosomal abnormalities. Expression of both
      human papillomavirus type 16 oncoproteins, E6 and E7, in normal human fibroblasts
      completely dissociates p21 and proliferating cell nuclear antigen from the
      quarternary cyclin-cyclin-dependent kinase (CDK) complexes present in normal
      cells, causes disruption of the cyclin D-CDK4 complex and replacement with a CDK4
      p16 complex, and leaves binary complexes of cyclin B1-CDC2 and cyclin A-CDK2
      intact. These results are identical to those observed in fully transformed cells.
      The expression of the individual oncoproteins dramatically affects the
      association of proliferating cell nuclear antigen into the complexes while
      leaving the total cellular levels unaltered. Expression of low-risk human
      papillomavirus has no effect on cyclin complexes. These findings provide evidence
      for the gross alteration of cyclin-CDK complexes in preneoplastic cells and links
      this alteration to the loss of genomic stability.

PMID- 8551643
TI  - Localization of rat small intestine glutamine synthetase using immunofluorescence
      and in situ hybridization.
AB  - Glutamine is an important energy source for small intestinal epithelial
      enterocytes and serves as a key precursor for de novo synthesis of purines and
      pyrimidines in these rapidly dividing cells. Although glutamine synthetase (GS)
      is known to be the major enzyme of glutamine biosynthesis, the precise
      localization of this enzyme in the small intestine is not known. Because
      glutamine is an important precursor for nucleic acids biosynthesis, we
      hypothesized that GS is preferentially expressed in the crypt region, which
      contains the rapidly proliferating cells in the small intestine. Accordingly,
      immunofluorescence with a specific polyclonal antibody and in situ hybridization
      using a riboprobe were performed to localize GS protein and mRNA, respectively,
      in adult rats. Both GS protein and GS mRNA were detected primarily in the crypt
      region. This finding suggests that GS is located in the region with the highest
      nucleotide synthesis and cell proliferation. This finding is in support of the
      use of parenteral glutamine in patients with severe mucosal injury affecting the
      crypts.

PMID- 8551644
TI  - Effects of deoxycholic acid and butyrate on mucosal prostaglandin E2 release and
      cell proliferation in the human sigmoid colon.
AB  - BACKGROUND: A high-fat, low-fiber diet resulting in increased excretion of fecal
      secondary bile acids is regarded as a major risk factor for colon cancer.
      Incubation of human colonic biopsies with the secondary bile acid deoxycholic
      acid (DCA) leads to hyperproliferation with expansion of the proliferative zone,
      ie, a biomarker of increased cancer risk. Antiproliferative effects on various
      colon cancer cell lines, however, were reported for butyrate (BUT), a
      fermentation product of dietary fiber. METHODS: In the following in vitro study
      we incubated biopsies from the normal sigmoid colon of 12 patients (age 55.8 +/-
      3.6 years) with 5 microM DCA or a combination of 5 microM DCA plus 10 mM BUT
      (DCA/BUT) and determined epithelial proliferation by bromodeoxyuridine
      immunohistochemistry. As a possible mediator for the DCA effects on colonic cell
      proliferation, mucosal prostaglandin E2 (PGE2) release into the incubation medium
      was measured by 125I-PGE2 radioimmunoassay. RESULTS: Incubation with DCA alone
      revealed a significantly higher labeling index for the whole crypt (.17 vs .11, p
      < .01) and for the upper 40% of the crypt (.05 vs .01, p < .01) compared with
      DCA/BUT. Mucosal PGE2 release during DCA/BUT incubation showed a trend toward
      lower values compared with DCA incubation (357.07 vs 434.29 pg/mg per hour; p =
      .07). CONCLUSION: The results indicate a normalization of DCA-induced
      hyperproliferation of colonic epithelium by butyrate that is not clearly mediated
      by PGE2. Considering that nutrition affects the luminal concentrations of DCA and
      butyrate, our findings may have implications for colonic carcinogenesis.

PMID- 8551645
TI  - Interrelation of intracellular proteases with total parenteral nutrition-induced
      gut mucosal atrophy and increase of mucosal macromolecular transmission in rats.
AB  - Total parenteral nutrition (TPN) is known to induce mucosal atrophy and to
      increase macromolecular transmission of the small intestine. The potential
      participation of various proteases in that process was investigated. Male Wistar
      rats were randomly divided into two groups: the TPN group (n = 11) received a
      standard TPN (250 kcal/kg per day, 1.78 g nitrogen/kg per day) and the FED group
      (n = 10) received a standard rat food for 1 week. This was followed by an
      examination of gut macromolecular transmission of fluorescein isothiocyanate
      dextran 70,000 (FITC-dextran) after intragastric injection and of the activities
      of gut mucosal cathepsins B, H, and L and of proteasome. Mucosal wet weight and
      protein content decreased significantly by TPN for 1 week. In both groups, the
      activities of all proteases in the ileum were significantly greater than in the
      jejunum. In the TPN group, cathepsin L and H activities in the ileum, and
      cathepsin B activity in both the jejunum and the ileum, were greater than those
      in the FED group. The portal concentration of FITC-dextran was higher than
      arterial and venous concentrations in the both groups. In the TPN group, the
      portal FITC-dextran concentration increased significantly compared with the FED
      group. In conclusion, active proteolysis is not associated with TPN-induced
      mucosal atrophy. Cathepsins activities in the ileum increase as a result of TPN.
      Interrelationship is implicated between increase of lysosomal protease activity
      and the deterioration of the intestinal barrier function, which permits
      macromolecular transmission.

PMID- 8551646
TI  - Malabsorption and villous atrophy in patients receiving enteral feeding.
AB  - BACKGROUND: The purpose of this study was to assess the structure and function of
      the small intestine before and after enteral feeding given via a percutaneous
      feeding gastrostomy (PEG). It is not known whether this method of feeding
      provides a good luminal drive to the small intestine. METHODS: Studies were
      performed of patients at the time of PEG placement, in a cross-sectional group
      after a period of feeding and in a smaller longitudinal subgroup. Enteral feeds
      were adjusted in volume and caloric content for each patient. Duodenal biopsies
      were taken during endoscopy for quantitative morphometry, and lactulose-rhamnose
      permeability tests were performed during the next day. Duodenal fluid was
      cultured quantitatively in the first study, and disaccharidases determined in the
      second study. RESULTS: The first study of 15 patients, who had enteral feeding
      for a median (range) period of 13 (8 to 104) weeks, showed partial villous
      atrophy with normal crypt length, no increase in duodenal bacteriology, and
      abnormal lactulose-rhamnose sugar permeability due to rhamnose malabsorption.
      These changes were also present in 38 similar patients before enteral feeding. A
      second study before enteral feeding showed lowered maltase activity (24
      patients), and similar intestinal permeability findings (22 patients). Twelve of
      these patients were followed longitudinally for 3 months of enteral feeding that
      maintained but did not improve nutrition, as assessed by body mass index and mid
      arm muscle circumference, and there was no change in duodenal morphometry (11
      patients), rhamnose malabsorption (4 patients), or disaccharidases (11 patients).
      CONCLUSIONS: These studies suggest villous atrophy was not due to an inflammatory
      enteropathy but resulted from a poor luminal "drive" associated with the enteral
      feeding. Enteral feeding maintained but did not improve nutrition status.

PMID- 8551647
TI  - Prevention of fatty liver and maintenance of systemic valine depletion using a
      newly developed dual infusion system.
AB  - BACKGROUND: Valine-depleted amino acid imbalance, while having a suppressive
      effect on tumor growth, may induce fatty liver. METHODS: We administered a valine
      depleted total parenteral nutrition (TPN) solution by the central venous route to
      non-tumor-bearing rats and examined the time course of the development of fatty
      liver. In an attempt to prevent this condition, we administered a continuous
      infusion of low concentrations of valine via the portal vein simultaneously with
      administration of central venous valine-depleted nutrition for 4 days. RESULTS: A
      marked accumulation of triglyceride was observed in the liver on day 4 of the
      administration of valine-depleted nutrition. It is speculated that such
      accumulation is the cause of fatty liver. The level of valine in the peripheral
      blood began to decrease soon after administration was begun and resulted in a
      state of systemic valine deficiency. Rats given 25% or more of the valine
      concentration in the standard TPN solution via the portal vein simultaneously
      with the administration of central venous valine-depleted nutrition, had a
      triglyceride level similar to that of the control group. The group given 50% or
      less of the valine concentration had a level of valine in the peripheral blood as
      low as that of the valine-depleted group, indicating the maintenance of a valine
      deficient state. CONCLUSION: Administration of low concentrations of valine via
      the portal vein simultaneous with central venous administration of valine
      depleted TPN solution may prevent fatty liver.

PMID- 8551648
TI  - Effect of enteral and parenteral nutrition on amino acid levels in cancer
      patients.
AB  - BACKGROUND: The syndrome of cancer cachexia can have a significant impact on
      response to therapy as well as on survival in cancer patients. Therapies directed
      at metabolic perturbations in cachectic patients are dependent on nutritional
      repletion and maintenance of adequate amino acid substrate levels. This study
      compares the ability of oral feeding, enteral nutrition, and total parenteral
      nutrition to alter plasma amino acid levels in cancer patients. METHODS: Patients
      with esophageal cancer were stratified by weight loss. Patients with < 20% weight
      loss were randomized to continue an ad libitum oral diet (group I) or to receive
      total parenteral nutrition (group II) for 2 weeks; patients with > 20% weight
      loss were randomized to receive either enteral nutrition (group III) or total
      parenteral nutrition (group IV) for 2 weeks. Plasma amino acid levels were
      measured before the study and again after 2 weeks of nutrition support. RESULTS:
      Before therapy, there was no difference between the groups in total or essential
      amino acid levels; however, patients in all groups had significantly lower total
      amino acid levels compared with those of normal controls. After 2 weeks of
      treatment, patients in group I and III showed no difference in individual,
      essential, or total amino acid levels. However, patients in groups II and IV
      showed significant increases in a number of individual amino acids as well as in
      essential and total amino acid levels after 2 weeks of TPN. CONCLUSIONS: Patients
      with esophageal cancer demonstrated significant alterations in amino acid
      profiles compared with those of normal controls. Total parenteral nutrition was
      superior to ad libitum oral feeding and jejunostomy feeding in repleting plasma
      amino acid levels.

PMID- 8551649
TI  - Comparative evaluation of the quantitative utilization of parenterally and
      enterally administered leucine and L-[1-13C,15N]leucine within the whole body and
      the splanchnic region.
AB  - BACKGROUND: The purpose of this study was to quantify the kinetic aspects of
      leucine metabolism in the whole body and within the splanchnic region when an
      amino acid mixture is administered by the enteral route as compared with
      administration by the parenteral route. METHODS: Seven chronically catheterized
      dogs were studied during an intragastric infusion of L-[1-13C,15N]leucine with
      0.24 g of complete amino acid mixture (kg-1.h-1) for 6 hours. The results are
      compared with those previously reported for nine dogs studied under essentially
      identical experimental conditions except that the tracer and amino acid mixtures
      were given by vein. RESULTS: At the whole body level, the various parameters of
      leucine metabolism (flux, oxidation, and disappearance into and release from
      proteins) were not significantly different among animals that were infused
      enterally and those that were infused parenterally. Leucine metabolism within the
      splanchnic region and gut was more extensive for enteral administration than for
      parenteral administration. For the splanchnic region, 31.4%, 27.9%, and 6.0% of
      enterally administered leucine was used for protein synthesis, deamination, and
      oxidization, respectively, compared with respective mean values of 19.5% (p <
      .001), 13.4% (p < .001), and 4.1% (p < .05) for parenterally administered
      leucine. For liver, 4.8% of enterally administered leucine was oxidized compared
      with 2.3% (p < .001) of parenterally administered leucine. These findings are
      qualitatively similar to those reported previously by us when comparing enteral
      and parenteral amino acid intakes but with an IV tracer infusion. CONCLUSION:
      Enteral administration seems to be more effective than an acute parenteral
      feeding regimen, at least in maintaining leucine (protein) balance in gut
      tissues.

PMID- 8551650
TI  - Influence of casein and casein hydrolysate diets on nutritional recovery of
      starved rats.
AB  - BACKGROUND: The aim of this study was to compare the effects of two diets, which
      differed in their protein source (casein and casein hydrolysate), on the
      nutritional recovery and intestinal repair of undernourished rats at weaning
      after a 3-day fasting period. Profound alterations in gut structure and signs of
      malnutrition appeared after the starvation period. METHODS: The casein
      hydrolysate was prepared by enzymatic hydrolysis and ultrafiltration. Rats were
      refed the casein-based or the casein hydrolysate-based diet for 96 hours. Normal
      fed male Wistar rats at weaning were given the casein diet for 7 days and were
      used as controls. Liver acetylcholinesterase, glutamate dehydrogenase activities,
      serum amino acid profiles, jejunal oligosaccharidases, alkaline phosphatase, and
      leucine aminopeptidase activities were studied. Intestinal permeability to intact
      proteins was also tested by using ovalbumin and measuring its concentration in
      serum. RESULTS: Intestinal and liver enzyme activities and serum amino acid
      profiles reached normal values after 96 hours of refeeding, regardless of the
      diet used. Glutamate dehydrogenase activity remained higher in both diet groups.
      Intestinal permeability to ovalbumin remained significantly increased only in the
      group refed the casein diet. CONCLUSIONS: Our results show that 4 days of
      refeeding are sufficient for complete intestinal recovery after fasting, provided
      the dietary protein source is a casein hydrolysate. We suggest that patients with
      malnutrition or malabsorption syndrome should be fed formula composed of
      enzymatic protein hydrolysates (because of their low antigenicity) rather than
      enteral formulas composed of intact proteins.

PMID- 8551651
TI  - Tissue manganese concentrations and antioxidant enzyme activities in rats given
      total parenteral nutrition with and without supplemental manganese.
AB  - BACKGROUND: Manganese is an essential but potentially toxic mineral. Parenteral
      administration of manganese via total parenteral nutrition (TPN) bypasses
      homeostatic mechanisms (intestinal absorption and presystemic hepatic
      elimination). Our objective in this study was to determine the effect of
      supplemental manganese in TPN solutions on manganese status in a rat model.
      METHODS: Male Sprague-Dawley rats underwent jugular catheterization and were
      given 61.0 +/- 0.4 g/d TPN solution providing 0.5 +/- 0.2 nmol manganese/g (Mn-;
      n = 6) or 16 +/- 3 nmol manganese/g (Mn+; n = 7) for 7 days. Reference rats (RF;
      n = 8) were fed a purified diet containing 1.3 mmol manganese/g. RESULTS: Liver
      manganese decreased in both TPN groups, but tibia, spleen, and pancreas manganese
      concentrations were greater in Mn+ rats than in Mn- or RF rats. Although no
      treatment differences were seen in heart or liver manganese superoxide dismutase
      activity, heart copper-zinc superoxide dismutase activity was lower in the Mn+
      rats than in Mn- or RF rats (p < .05). Glutathione peroxidase activity was
      depressed in livers of both Mn- and Mn+ rats relative to RF rats (p < .0001),
      which was not due to selenium deficiency. CONCLUSIONS: Supplemental parenteral
      manganese is taken up to a greater extent by peripheral tissues than the liver.
      In this first report of antioxidant enzyme activities in animals maintained with
      TPN, we found that TPN as well as supplemental manganese can influence
      antioxidant enzyme activities. We conclude that it is generally unnecessary and
      potentially toxic to supplement TPN solutions with manganese during short-term
      usage.

PMID- 8551652
TI  - Metabolic effects of arginine in a healthy elderly population.
AB  - Recently there has been much interest in the use of arginine to stimulate immune
      responses and to promote wound healing. In the present study, the effect of an
      oral supplementation with arginine on the metabolism of 45 healthy, nonsmoking,
      elderly volunteers was investigated. Subjects were divided into two groups that
      received either arginine aspartate (17 g free arginine) (n = 30) or a placebo (n
      = 15). The supplements were taken for a period of 14 days. Dietary intake of food
      was not controlled. Blood chemistry, lipid profiles, and as an index of
      nutritional status, serum insulin-like growth factor-1 levels and nitrogen
      balance were compared before and after supplementation. Two weeks of arginine
      supplementation led to a significant elevation of serum insulin-like growth
      factor concentrations and an improved and positive nitrogen balance (2.0 +/- 0.41
      g N) when compared with controls (0.11 +/- 0.47 g N; p = 0.0114). In addition the
      arginine-supplemented group demonstrated a decreased total serum cholesterol with
      a reduction in the low-density lipoprotein but not the high-density lipoprotein
      fraction resulting in a increase in the ratio of low- to high-density lipoprotein
      fraction. No adverse effects were observed at this dosage of arginine. The data
      suggest that oral arginine supplementation may be used safely in elderly humans.

PMID- 8551653
TI  - Altered mental function during intravenous infusion of recombinant human insulin
      like growth factor 1.
AB  - Recombinant human insulin-like growth factor-1 (rhIGF-1) is currently used
      experimentally to treat patients with insulin-resistant diabetes mellitus,
      impaired growth, protein malnutrition, and osteoporosis. We report here the case
      of a marked transient alteration in consciousness in a healthy 22-year-old man
      who was given an IV infusion of a relatively low dose of rhIGF-1 for 1 hour. This
      individual developed the sudden onset of dizziness, nausea, coldness, air hunger,
      and pallor. He became unresponsive to simple questions and experienced
      diaphoresis, a feeling of warmth, and paresthesias. Although there was a mild
      fall in heart rate and blood pressure, these hemodynamic effects did not appear
      sufficient to cause the altered mentation. There were no changes in serum
      glucose, phosphorus, or potassium that could seem to account for these events.
      This individual recovered completely several minutes after stopping the rhIGF-1
      infusion.

PMID- 8551654
TI  - Nitric oxide, sepsis, and arginine metabolism.
AB  - Nitric oxide is one of the most versatile molecules produced by mammalian cells.
      Its role in sepsis and inflammation has been the subject of intense investigation
      since its discovery as a cell product in 1987. The role of arginine in sepsis and
      trauma has also received considerable attention, but most of the earlier studies
      on arginine preceded the studies on nitric oxide and the discovery that arginine
      serves as the nitrogen donor for nitric oxide synthesis. This review will explore
      the role that nitric oxide plays in sepsis and the effects of arginine metabolism
      on nitric oxide synthesis.

PMID- 8551655
TI  - Percutaneous endoscopic gastrojejunostomy: a dual center safety and efficacy
      trial.
AB  - Although jejunal tube placement through a percutaneous endoscopic gastrostomy
      (PEG) has not been proven to be preferable to PEG feeding, it would be
      theoretically advantageous for those patients prone to gastrointestinal
      aspiration. However, reliable placement of a small bowel feeding tube through a
      PEG has been technically difficult. We have previously reported successful
      placement of a percutaneous endoscopic gastrojejunostomy (PEG/J) with minimal
      complications. These results are in contrast to other series that report
      technical difficulty, frequent tube dysfunction and gastric aspiration. We
      describe an over-the-wire PEG/J technique performed by multiple operators at two
      medical centers. Gastrostomy tube placement was successful in 94% of patients.
      Initial placement of the jejunal tube was successful in 88% of patients. Second
      attempts were 100% successful. The average procedure time was 36 minutes. The
      distal duodenal and jejunal placement of the jejunal tube resulted in no episodes
      of gastroduodenal reflux. Complications included jejunal tube migration (6%),
      clogging (18%), and unintentional removal (11%). The majority of patients were
      ultimately converted to either oral or intragastric feedings. We conclude that
      the PEG/J system is a reliable, reproducible method of small bowel feeding and is
      associated with no episodes of tube feeding reflux when the jejunal tube is
      positioned in the distal duodenum or beyond. Furthermore, it provides a temporary
      nutritional bridge for those patients who are later transitioned to either PEG or
      oral feeding.

PMID- 8551656
TI  - Intraoperative placement of the nasoenteric feeding tube: a practical
      alternative?
AB  - BACKGROUND: The provision of early postoperative enteral feeding may be enhanced
      by the placement of enteral feeding access during celiotomy, but surgeons are
      often reluctant to pursue this option because of the extra effort required.
      METHODS: We conducted a retrospective review of our 2-year experience with 60
      sequential intraoperative nasoenteric feeding-tube placements and included data
      on demographics, diagnosis, surgery, type of feeding tube, formula, tolerance,
      and complications. Our surgeons placed intraoperative nasoenteric feeding tubes
      at their discretion in a variety of subjects who were undergoing elective or
      urgent celiotomies. RESULTS: The surgeries largely involved the upper
      gastrointestinal tract, and feeding-tube placements were readily accomplished.
      The majority of patients received enteral feedings within 3 postoperative days
      and achieved feeding rates of 50 mL/h or greater. The average duration of feeding
      tube use was 1 week, accounting for 399 feeding days overall. There were no
      serious complications attributable to feeding-tube placement or use, but
      inadvertent tube removal by patients or staff was a limitation. CONCLUSIONS:
      Intraoperative placement of the nasoenteric feeding tube may be a reasonable
      option for treating the surgical patient at nutritional risk who faces a limited
      course of impaired oral intake postoperatively.

PMID- 8551657
TI  - Artificial nutrition support terminology.

PMID- 8551658
TI  - Total parenteral nutrition catheters.

PMID- 8551659
TI  - Don't malnourish the obese!

PMID- 8551660
TI  - Modification of chemo-radiosensitivity of a human lung cancer cell line by
      introduction of the glutathione S-transferase pi gene.
AB  - Recent studies have suggested that glutathione S-transferase pi (GST-pi) may play
      a role in determining tumor sensitivities to cytotoxic drugs. In order to better
      understand the role of this enzyme in chemo- and/or radioresistance of lung
      cancer cells, we examined whether introduction of GST-pi cDNA into a chemo- and
      radiosensitive lung cancer cell line altered its sensitivities to various
      chemotherapeutic agents and/or ionizing radiation, which are often used in the
      management of lung cancers. Modestly increased resistance of the GST-pi
      transfectants preferentially to sublethal damage caused by ionizing radiation as
      well as to adriamycin (ADM) was observed. In contrast, resistances to cisplatin
      (CDDP), etoposide (VP-16), irinotecan hydrochloride (CPT-11) and paclitaxel were
      virtually unaltered. These results suggest that GST-pi may not play a major role
      in chemo- and radioresistance of lung cancers, although it could afford selective
      and limited protection against ADM- and ionizing radiation-induced damage.

PMID- 8551661
TI  - Relationship of esophageal dysplasia to associated head and neck cancer in
      patients with esophageal carcinoma.
AB  - To investigate the relationship between esophageal dysplasia and the development
      of both esophageal cancer (EC) and head and neck cancer (HNC), a
      clinicopathological study was performed in 113 patients with EC who underwent
      esophagectomy without any preoperative treatment. The incidence of dysplastic
      lesions in the resected esophagus was determined by a whole-organ stepwise
      cutting method. Synchronous or metachronous primary HNC was present in 25
      patients, all of whom were male (Group A) and absent in both 70 male patients
      (Group B) and 18 female patients. A total of 628 dysplastic lesions were found in
      79 patients; 67 of them were graded as carcinoma in situ (CIS) in 26 patients, 44
      as severe dysplasia (SD) in 16 patients, 182 as moderate dysplasia (MOD) in 59
      patients, and 335 as mild dysplasia (MID) in 58 patients. The incidence of CIS,
      SD and MOD was low in females, slightly increased in Group B, and markedly
      increased in Group A, and the differences between Group A and Group B and between
      Group A and females were statistically significant. There was a sex difference in
      smoking and alcohol consumption, only a few smokers or drinkers being female,
      whereas there was no significant difference between Groups A and B in smoking and
      alcohol consumption. CIS, SD or MOD in the esophagus appear to be closely related
      to both EC and HNC, and patients with EC associated with CIS, SD or MOD are at
      increased risk of developing HNC.

PMID- 8551662
TI  - Serum cytokine level fluctuations in chemotherapy-induced myelosuppression.
AB  - We have reported that serum granulocyte colony-stimulating factor (G-CSF) and
      interleukin-6 (IL-6) levels rise in patients with chemotherapy-induced
      myelosuppression. The aim of the present study was to determine whether other
      cytokines that function at different hematopoietic stages also fluctuate during
      chemotherapy-induced myelosuppression and whether the extent of cytokine level
      fluctuations correlate with myelosuppression severity. Fifteen patients
      participated in the study. Serum levels of stem cell factor (SCF), interleukin
      (IL)-1 alpha, IL-6, IL-3, granulocyte-macrophage CSF (GM-CSF) and G-CSF were
      analyzed before chemotherapy and during the myelosuppressive stage and
      correlations between cytokine levels and myelosuppression severity were examined.
      The results showed that both serum G-CSF and IL-6 levels rose in patients with
      chemotherapy-induced myelosuppression. The prechemotherapy serum G-CSF and IL-6
      levels correlated well with their respective elevated levels during the
      myelosuppressive stage. The myelosuppression severity also correlated well with
      the extent of serum G-CSF level elevation. The serum IL-6 and G-CSF levels during
      the myelosuppressive stage correlated significantly. Serum SCF levels did not
      fluctuate significantly during myelosuppression, and IL-1, IL-3 and GM-CSF were
      rarely detected in serum even after chemotherapy. In the present study, the roles
      of IL-1 alpha, SCF, IL-3 and GM-CSF chemotherapy-induced myelosuppression were
      not clear.

PMID- 8551663
TI  - Histologic growth patterns of metastatic carcinomas of the liver.
AB  - One hundred autopsied livers containing metastatic cancers were studied
      pathologically. Macroscopically, the cancers were of the multinodular type in
      65.0% of cases, massive type in 17.0% and portal tract type in 8.0%. Among liver
      metastases from colon and lung cancers, most cases showed predominantly
      intraparenchymal growth (92.3% and 87.5%, respectively). In contrast, among liver
      metastases from gallbladder/bile duct cancer, intraparenchymal growth was less
      frequent (35.7%). With regard to the histologic growth pattern at the boundary of
      the liver metastases, in micrometastases less than 1 mm in diameter a replacement
      growth pattern was predominant among metastases from lung, colon and pancreas
      cancers (69.7%, 79.3% and 66.7%, respectively), whereas a sinusoidal growth
      pattern was predominant in those from gastric and gallbladder/bile duct cancers
      (48.5% and 66.7%). Among macrometastases of the liver over 20 mm in diameter, an
      expansive growth pattern was predominant, irrespective of the cancer primary
      site. Thus metastatic liver cancers showed changes in growth patterns according
      to the size of the metastatic tumors.

PMID- 8551664
TI  - Diagnostic utility of endoscopic ultrasonography for preoperative rectal cancer
      staging estimation.
AB  - The preoperative staging accuracy of endoscopic ultrasonography (EUS) was
      assessed in 38 rectal cancer patients who underwent rectal EUS and curative
      surgery from July 1992 to September 1994. We used a GF-UM20 instrument with both
      12- and 7.5-MHz transducers. Compared with the histological findings, the
      diagnostic accuracy rate for EUS was 76% (29/38) for the invasion depth and 85%
      (sensitivity) and 72% (specificity) for level one lymph node metastasis,
      resulting in an overall preoperative staging accuracy of 74% (28/38). The
      diagnostic accuracy of invasion depth was poor (only 45%: 5/11) in cases shown
      histologically to be a1 (tumor invasion through muscularis propria into parietal
      fat), but ranged from 90 to 100% when the a1 cases were excluded. The diagnostic
      accuracy for level one lymph node metastasis was proportional to the nodal size.
      The size of lymph nodes that had been diagnosed as metastatic and non-metastatic
      (P < 0.05) differed significantly. Eighteen (86%) of the 21 metastatic nodes with
      histologically massive invasion were detected preoperatively by EUS. Eight of the
      11 undetected metastatic nodes were either less than 4 mm in diameter or showed
      only slight invasion. Most (81%) of the level one metastatic nodes larger than 5
      mm were found. The worst preoperative staging diagnostic accuracy was for stage
      II cases (63%: 5/8), and in four of the 10 misdiagnosed cases, the stage was
      underestimated due to slight nodal invasion or skip metastasis (2 cases each).
      Although it was difficult to diagnose nodal metastasis correctly in these cases,
      preoperative staging using EUS was considered useful for diagnosing almost 80% of
      our rectal cancer cases.

PMID- 8551665
TI  - An early phase II study of etoposide (VP-16) in advanced gastric cancer.
AB  - An early phase II study was conducted to evaluate the anti-tumor effects and
      toxicity of etoposide in patients with unresectable or relapsed advanced gastric
      cancer. From April 1991 to December 1992, 13 patients were enrolled into this
      study; one was subsequently considered ineligible. Before enrollment, all the
      patients had been treated with chemotherapy which did not include etoposide.
      Etoposide (100 mg/m2/day) was administered as an intravenous infusion over 120
      min for five consecutive days and was repeated every four weeks. Seven patients
      received one course of this therapy and the remaining five received two. No
      patient showed a complete or a partial response. No change and progressive
      disease were observed in three and nine patients, respectively. The clinical
      toxicities (grade 3-4; WHO) of leukocytopenia, anemia and alopecia occurred in
      50, 42, and 42% of the patients, respectively. We conclude that this dose of
      etoposide administered according to the present schedule is ineffective in
      previously treated patients with advanced gastric cancer.

PMID- 8551666
TI  - Dose-response relationship between coffee and the risk of pancreas cancer.
AB  - A case-control study was conducted and previous epidemiological data were
      reviewed in order to investigate the dose-response relationship between coffee
      and the risk of pancreas cancer. The case-control study was community-based and
      was carried out in Hokkaido, Japan, employing 141 patients with pancreas cancer
      and 282 controls (two for each case) matched for sex, age and place of residence.
      The dose-response relationship between coffee (cups/day) and the relative risk of
      this disease formed a U-shaped curve. The lowest relative risks (0.18 for male
      and 0.53 for female) were found among "occasional" drinkers. Epidemiological
      articles published between 1981 and 1993 were selected from Index Medicus using
      the two key words "coffee" and "pancreas cancer". In many of the previous case
      control studies the curve of the dose-response relationship was also U-shaped,
      when the relative risks were calculated specifically using four or five levels of
      coffee dose. The nadirs of the relative risks, most of which ranged from 0.5 to
      0.7, were found most frequently at small doses (1-2 or 3-4 cups/day). The results
      of meta-analysis of these studies formed a U-shaped curve. Studies of other types
      showed almost the same results. Thus it appears that small amounts of coffee
      might prevent pancreas cancer, whereas large amounts might cause the disease.

PMID- 8551667
TI  - Acromegaly caused by growth hormone-relating hormone in a patient with multiple
      endocrine neoplasia type I.
AB  - A 51-year-old Caucasian man with multiple endocrine neoplasia (MEN) type I
      syndrome presented with clinical features of acromegaly. Exploration of the
      pituitary gland only revealed somatotrophic hyperplasia and his plasma growth
      hormone (GH) levels remained elevated. Production of growth hormone-releasing
      hormone (GHRH) by an ectopic tumor was suspected and, after additional
      investigations, a large pancreatic tumor was detected and removed. As the
      pancreatic tail contained multiple (occult) adenomas, lifelong follow-up was
      considered necessary. The patient has been recurrence-free for 10 years. All 19
      living relatives of this patient were analysed for endocrine disorders related to
      MEN I syndrome. A brother was found to suffer from peptic ulcer disease caused by
      hyperparathyroidism and, during screening for other organ involvement associated
      with the MEN I syndrome, two tumors were found, one (4 cm) in the pancreatic tail
      region and one in the right adrenal gland. To date, six other family members have
      been found to suffer or have suffered from hyperparathyroidism and in a male
      subject, a prolactinoma and hyperparathyroidism were detected.

PMID- 8551668
TI  - Endobronchial lipoma: a report of three cases.
AB  - Although lipomas are common benign neoplasms of soft tissue, endobronchial lipoma
      is rare. We have treated three patients with endobronchial lipoma over the five
      years. In two of them lesions were located in segmental or subsegmental bronchi
      and produced no symptoms. There are very few such cases reported in the English
      medical literature. In the first case, pneumonectomy was performed because of
      destruction of the lung due to recurrent pneumonia. The second case had no
      symptoms and the tumor was located at the bifurcation of right B4a and B4b. A
      right middle lobectomy was performed, because the distal end of the tumor could
      not be visualized by fiberoptic bronchoscopy. In the third case, which was a case
      of lung cancer, an endobronchial lipoma was found during fiberoptic bronchoscopy,
      and was completely removed endoscopically. Due to their benign nature,
      endobronchial lipomas should be initially treated with endoscopic surgery or
      endoscopic laser vaporization. Nevertheless, if the tumor is large and dumbbell
      shaped on tomography or CT, endoscopic procedures are not appropriate.
      Furthermore, if destructive pulmonary change due to the tumor is severe, the
      remaining peripheral lung will not recover after endoscopic procedures, even if
      they are removed successfully. When the biopsy specimen is too small to allow
      evaluation of the whole tumor, surgical resection should also be considered for
      definitive diagnosis.

PMID- 8551669
TI  - Circulating parathyroid hormone-related protein (109-141) in malignancy
      associated hypercalcemia.
AB  - For differential diagnosis between hypercalcemia-induced bone metastasis and
      humoral hypercalcemia of malignancy (HHM), serum parathyroid hormone-related
      protein (PTHrP) concentrations were measured in normal subjects and patients with
      malignancy-associated hypercalcemia according to the presence or absence of bone
      metastasis, using a new sensitive PTHrP(109-141) radioimmunoassay system. The
      serum PTHrP(109-141) levels in all of 14 patients without bone metastasis were
      significantly higher than those in normal subjects. However, in four patients
      with hypercalcemia associated with bone metastasis the levels were nearly the
      same as those in normal subjects. The time course in two hypercalcemic patients
      with esophageal carcinoma revealed that serum PTHrP(109-141) levels were elevated
      before hypercalcemia developed and that changes in PTHrP(109-141) and corrected
      serum calcium levels were significantly correlated. These findings suggest that
      determination of serum PTHrP(109-141) may be clinically important not only for
      differential diagnosis of HHM but also as a useful predictive marker of
      hypercalcemia.

PMID- 8551670
TI  - [Effects of lifestyle on health status].
AB  - We followed up 2,148 male and female workers for 6 years and assessed the
      relationship between lifestyle and physical health status. The physical health
      status was significantly higher in the group with a good lifestyle than in the
      group with a poor lifestyle. When we analyzed the effects of lifestyle on chronic
      diseases using multiple logistic regression, the incidence of gastric and
      duodenal ulcers and cardiovascular diseases was several times higher in the group
      with a poor lifestyle than in the group with a good lifestyle. We also introduced
      several biological markers, including natural killer (NK) cell activity and
      chromosome alterations such as sister chromatid exchanges, chromosome aberrations
      and micronucleus formation, to predict the participants' future health status.
      All these markers were significantly correlated with lifestyle. Our findings
      indicate that lifestyle is the most important environmental factor which
      quantitatively affects the development of adult diseases and the changes of
      biological markers.

PMID- 8551671
TI  - [The screening of hepatitis virus and its efficacy].
AB  - 1. Infection of hepatitis A virus (HAV) was prevented with hepatitis A vaccine.
      High risk groups of HAV infection should be inoculated this vaccine because
      Japanese peoples less than 40 years old didn't have immunity for HAV. 2.
      Infection of hepatitis E virus (HEV) was scarcely observed in Japan. 3. Infection
      of hepatitis B virus (HBV) by blood transfusion was eradicated after the
      screening with anti-HBc antibody for blood donors. And maternal transmissions of
      HBV and infections of HBV in hospital were protected by HB-globulin and hepatitis
      B vaccine. 4. Infection of hepatitis D virus (HDV) was protected by HB-globulin
      and hepatitis B vaccine. 5. Infection of hepatitis C virus (HCV) by blood
      transfusion markedly decreased after the screening with anti-HCV for blood
      donors. We can't prevent a maternal transmission of HCV but its frequency is low
      (about 10%). And acute hepatitis C due to an infection of HCV in hospital can be
      prevented by the treatment with interferon in the Workmen's Accident Compensation
      Insurance.

PMID- 8551672
TI  - [Postgravid health care and laboratory tests].
AB  - Various diseases often occur after delivery but the systemic examinations have
      not been studied before. Thyroid dysfunction frequently (4.4%) occurs after
      delivery through an immune rebound mechanism. If postpartum women complain of the
      symptoms caused by thyrotoxicosis (palpitation, weight loss, increased sweating,
      finger tremor, fatigue) or hypothyroidism (edema, cold intolerance, hoarseness,
      sleepiness, fatigue), it is essential to examine thyroid hormones, thyroid
      stimulating hormone, anti-thyroid microsomal antibody (MCHA) and anti-TSH
      receptor antibody. To predict who will develop postpartum thyroid dysfunction,
      the measurement of MCHA during pregnancy is useful because 62% of the subjects
      with positive MCHA show thyroid dysfunction after delivery. The individuals at
      high risk of postpartum onset of Graves' thyrotoxicosis can be found early in
      their pregnancy by the detection of thyroid stimulating antibody (TSAb). Other
      autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus,
      autoimmune hypophysitis and so on, also could develop after delivery. These
      findings indicate that laboratory tests in the postpartum period are essential to
      diagnose postpartum onset of autoimmune diseases and the measurement of
      autoantibodies in early pregnancy is useful for prediction of their onset in the
      postpartum period.

PMID- 8551673
TI  - [Echocardiographic examinations for mass-screening of cardiovascular
      abnormalities].
AB  - We evaluated the echocardiographic techniques for detecting left ventricular
      hypertrophy, mitral valve prolapse, and underlying abnormalities of nonspecific T
      wave changes on electrocardiograms during mass-screening medical examinations.
      The sensitivity and specificity of the electrocardiographic voltage criteria of
      Sokolow et al. for detecting left ventricular hypertrophy determined from the
      actual left ventricular wall thickness measured by echocardiograms in 759 young
      men, were only 61% and 54%, respectively. The diagnosis of left ventricular
      hypertrophy should be based on echocardiographic measurements even during mass
      screening medical examinations. Mitral valve prolapse was detected in 25 (1.2%)
      of 2016 young healthy subjects. The mitral valve prolapse may not be a rare
      abnormality even in apparently normal subjects. Of 5217 consecutive subjects who
      underwent mass-screening medical examinations, 56 subjects had a mild T wave
      abnormality which was not explained by any of ischemic heart disease,
      hypertension, valvular heart disease, cardiomyopathy, and other systemic
      abnormalities. Careful echocardiographic examinations revealed regional or mild
      left ventricular hypertrophic lesions in 31 (55%) of these 56 subjects. We
      conclude that echocardiographic techniques are useful for detecting left
      ventricular hypertrophy and mitral valve prolapse and for elucidating the
      underlying abnormalities of nonspecific T wave changes during mass-screening
      medical examinations.

PMID- 8551674
TI  - [Recent progress in the diagnosis of thyroid diseases].
AB  - The diagnosis of thyroid diseases is mainly divided into three categories:
      morphological, functional and etiological diagnoses. Great progress has recently
      been seen in each field. For example, in the functional diagnosis, improvement of
      sensitivities and development of non-radioimmunoassays have been achieved in the
      measurement of hormone level. Especially, improvement of thyrotropin (TSH)
      measurement has greatly contributed to precise evaluation of thyroid function. In
      the etiological diagnosis, marked improvements have been made by genetic
      analyses. Mutations of genes of hormones, their receptors and other proteins
      related to thyroid function have been revealed as causes of various thyroid
      disorders, such as cretinism, hyperthyroidism and tumors. Immunological analyses
      also showed significant progress, i.e., improvement of anti-thyroglobulin and
      anti-thyroid peroxidase antibody measurements. It is also necessary for all three
      diagnostical approaches to be improved concomitantly in the future.

PMID- 8551675
TI  - [Progress in the diagnosis of endocrine and metabolic disorders: hyperlipidemia].
AB  - Hyperlipidemia is one of the risk factors for coronary atherosclerosis and the
      establishment of its simple etiological diagnosis is crucial. Hyperlipidemia can
      be classified into primary and secondary hyperlipidemia. Primary hyperlipidemia
      includes familial lipoprotein lipase (LPL) deficiency, familial
      hypercholesterolemia (FH), familial type III hyperlipidemia, and familial
      combined hyperlipidemia. Many genetic mutations have been identified in patients
      with familial LPL deficiency and FH. An ELISA kit has been established to
      determine LPL mass levels, using monoclonal antibodies against LPL. FH is a
      deficiency of LDL receptor and is characterized by marked hypercholesterolemia
      and Achilles tendon xanthomas. It can be diagnosed by an LDL receptor assay,
      using 125I-LDL in skin fibroblasts. However, the diagnosis can be made easily by
      measuring the uptake of DiI-LDL by peripheral lymphocytes. Familial type III
      hyperlipidemia is a genetic disorder characterized by the presence of a broad
      beta pattern in lipoprotein electrophoresis and is based upon the abnormality of
      apo E isoform (apo E2/2). Apo E4 has been shown to be associated with late-onset
      Alzheimer's disease. Cholesteryl ester transfer protein (CETP) deficiency is
      characterized by a marked hyperalphalipoproteinemia and various abnormalities in
      the size and composition of LDL and HDL. Two common mutations in the CETP
      deficiency have been identified; an intron 14 splicing defect and D442: G
      missense mutation. These mutations account for at least one half of hyper-HDL
      cholesterolemia in the Japanese. We have recently identified an area (Omagari
      City, Akita) where the frequency of heterozygotes for the intron 14 splicing
      defect is approximately 28% of the general population.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8551677
TI  - [Evaluation of multiple Pseudomonas aeruginosa strains with different
      characteristics in clinical specimens; combined results from serotyping, drug
      susceptibility and enzyme production].
AB  - Multiple Pseudomonas aeruginosa strains with different characteristics are
      occasionally isolated from a clinical specimen. Therefore, more than five
      isolated colonies of P. aeruginosa obtained at random from each clinical specimen
      (47 sputa, 18 urine, 10 pus and 8 others). These were investigated for serotype,
      drug susceptibility to eight antimicrobial agents and productivity of enzymes,
      such as protease and elastase. The specimens with multiple serotype colonies were
      shown in 17% of the sputa, 11% of the urine and 10% of the pus. 45.7% of the
      specimens with single serotype colonies exhibited more than two different
      patterns of enzyme productivity and so did 47.1% different patterns of drug
      susceptibility. Single serotype strains of P. aeruginosa with different
      characteristics of these tests were demonstrated in 81.3% of the urine, 73.6% of
      the sputum, 50.0% of the pus and 66.7% of others. We conclude that it is
      important to recognize the possible existence of multiple P. aeruginosa strains
      with different patterns of the enzyme productivity and drug susceptibility,
      regardless of single serotype, in clinical specimens.

PMID- 8551676
TI  - [Role of renin angiotensin system in the vasopressor mechanisms of hypertension-
      gene analyses and tissue renin angiotensin system].
AB  - The renin angiotensin system is one of the most important humoral factors
      underlying the mechanism of hypertension. The genes constituting the renin
      angiotensin system have been expected to be candidates for essential
      hypertension. DNA polymorphisms of angiotensinogen and angiotensin II type 1
      receptor genes are reported to be significantly related with the incidence of
      human hypertension, but further investigation is needed to clarify the
      relationship between the genes of the renin angiotensin system and hypertension.
      The renin angiotensin system exists not only in circulating blood, but also in
      extrarenal organs and tissues. Tissue renin angiotensin systems in the brain,
      blood vessels, and adrenal glands are considered to play important roles in the
      pressor mechanisms in low renin as well as high renin hypertension. Gene
      expressions of the constituents of the tissue renin angiotensin system are
      affected in part by circulating angiotensin II, but they are regulated mostly by
      their own specific control mechanisms in each organ and tissue. In future,
      laboratory tests in clinical medicine may be necessary to determine the DNA
      polymorphisms and tissue gene expression of renin angiotensin system, in deciding
      the diagnosis, prognosis and therapy of hypertension.

PMID- 8551678
TI  - [O-serotypes, biotypes and antimicrobial susceptibilities of Serratia marcescens
      isolates from clinical specimens: 4th report].
AB  - The clinical isolates of Serratia marcescens in The Showa University Fujigaoka
      Hospital in the period V during the 3 years from 1991 April to 1994 March were
      epidemiologically investigated by determining O-antigens, biotypes and
      antimicrobial susceptibilities. The isolates were collected, while the
      consumption of beta-lactam antibiotics, new quinolones, and aminoglycosides in
      the hospital had not changed significantly since 1991. The urease positive O3
      strains were predominantly isolated in the period II to IV during the 9 years and
      3 months from 1982 January to 1991 April and were more resistant to third
      generation cephalosporins and the other drugs such as new quinolones and
      aminoglycosides than the other O-serotype strains. However, the urease negative
      O14 strains, unlike such O3 strains, were predominantly isolated in the period V
      and were more resistant to the above mentioned drugs than the other O-serotype
      strains, indicating that they had higher resistance rates for carbenicillin,
      latamoxef, ceftizoxime, cefoperazone, cefpirome, tobramycin, dibekacin,
      gentamicin and fosfomycin than the O3 strains in the period IV during the two
      years and three months from 1989 January to 1991 March. The hospital wards in
      which the O14 strains were mainly isolated were the departments of urology,
      general surgery, orthopedic surgery, haematology, and internal secretion and
      kidney medicines, corresponding to those in which the isolation number of the O3
      strains decreased in the period V. These findings suggest that S. marcescens
      resident in the hospital inherits multiple drug resistance by changing the
      biotype and O-serotype.

PMID- 8551679
TI  - [Improved method for detection and subtyping of HCV.RNA by nested polymerase
      chain reaction].
AB  - Amplification of hepatitis C virus RNA (HCV.RNA) by the reverse transcription
      nested polymerase chain reaction (RT-nested PCR) has been successfully applied to
      the detection for HCV.RNA in blood and its subtyping. Primers in the 5'-noncoding
      region (5'-NC) for detecting HCV.RNA and type-specific primers in the core region
      for subtyping HCV were used in this study. When 20 cycles of amplification with
      outer primers and another 20 cycles with inner primers were employed, good
      results were obtained in both specificity and sensitivity of nested PCR,
      especially by a single tube method. Of 755 subjects suspected of being infected
      with HCV, HCV.RNA was detectable in 488 (80.3%) of 608 subjects who were positive
      for HCV antibody and in 70 (47.6%) of 147 subjects who were negative; the total
      detection ratio was 73.9%. The distributions of HCV subtypes, designated as I,
      II, III, IV and mixed type (II+III, II+IV and III+IV), were 0, 85.0, 6.1, 4.8 and
      4.0% respectively. Additionally, sensitivity in subtyping HCV.RNA was more
      improved by a single tube method. Using two primer sets (A:#32/#48 and B:
      #33/#48) prepared within the 5'-NC region, it was shown that the positivity of
      HCV.RNA was increased. Of 315 subjects, 232 (73.2%) were positive for HCV.RNA
      with both of A and B primer sets, and 20 or 22 were positive with either A or B
      primer set, thus indicating that a combination of these two primer sets increased
      the detection ratio of HCV.RNA approximately to 80%.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8551680
TI  - [Specific quantification of gamma-seminoprotein-alpha 1 antichymotrypsin complex
      in serum by monoclonal antibody-based enzyme immunoassay].
AB  - Gamma-seminoprotein (gamma-Sm) is one of the serine proteinases in seminal
      plasma, and is well known as a tumor marker of prostate cancer. In the blood, a
      major portion of gamma-Sm combines with alpha 1 antichymotrypsin (ACT), a serine
      proteinase inhibitor. We developed a sensitive enzyme immunoassay (EIA) for the
      gamma-Sm-ACT complex using two different monoclonal antibodies (MoAbs). One MoAb,
      prepared against gamma-Sm, is used for the capture, and the other, prepared
      against ACT, is conjugated with horseradish peroxidase and used for detection.
      The detectable range of this assay in clinical applications was from 0.2 to 50
      units/ml. The intra-assay coefficients of variation (CV%) obtained from ten
      repeated assays of three sera were 3.6 to 5.5%. The mean gamma-Sm-ACT complex
      concentration in the sera of normal individuals was determined to be 0.86 +/-
      0.11 units/ml for males (n = 50) and 0.11 +/- 0.08 units/ml for females (n = 54).
      There was no significant increase in the level of the complex with increasing age
      in males. The ratio of the gamma-Sm-ACT complex to free gamma-Sm tended to be
      significantly higher in patients with prostate cancer than in those with benign
      prostatic hyperplasia.

PMID- 8551681
TI  - [Remnant-like particles-cholesterol (RLP-C) assay and its clinical application to
      lipid tests in a postprandial as well as fasting state].
AB  - It was during the past few years that postprandial hyperlipidemia is believed to
      be more closely related to a risk for coronary artery disease. However, the high
      variability in the postprandial triglyceride (TG) levels could have made
      overlooked such diagnostic value in estimating an individual's risk for coronary
      artery disease. To minimize the impact of such variability, the remnant
      lipoproteins, TG-rich lipoproteins, might be measured in cholesterol using
      remnant-like particles (RLP-C) assay as a more reliable marker. In place of the
      previous cholesterol reagent (CHOD-Iodine) in RLP-C assay, the RLP-C assay was
      improved by employing a new cholesterol reagent (POD-EMSE). The correlation
      between these two assays was high (r = 0.978). The variations in RLP-C levels in
      healthy normolipidemic subjects was within 7.5mg/dl in a day. In oral-fat loading
      test, the variations of RLP-C levels in healthy subjects were also within
      7.5mg/dl. However, patients with coronary artery disease showed much higher
      levels (over 7.5mg/dl) of RLP-C during the test. In conclusion the RLP-C assay
      can be used for the measurement of remnant lipoproteins in serum prepared from
      the fasting as well as postprandial states for predicting subjects who may be at
      risk of coronary artery disease.

PMID- 8551682
TI  - [Recovered state of iron in female blood donors--after taking an iron
      supplement].
AB  - An iron supplement was given to female blood donors to prevent iron deficiency
      after blood donation. The levels of items related to red blood cells and serum
      ferritin (S-Fer) among 17 iron-takers and 31 non-iron-takers were analyzed
      continuously. In most of the non-iron-takers, the S-Fer levels did not recover
      within four weeks after the donation of 200ml or 400ml of blood. In the
      approximately half of the donors, hemoglobin (Hb) levels did not recover either.
      However, in 59% of those taking iron supplements three times the amount of iron
      lost by donation, the levels of Hb and S-Fer recovered within two weeks. In the
      remaining 41%, the Hb levels recovered within four weeks by taking the iron
      supplement. Four weeks after blood donation, the incidence of iron deficiency
      anemia among the non-iron-takers increased from 13% to 23% and the incidence of
      latent iron deficiency among the non-iron-takers increased from 32% to 42%.
      However, the incidence of iron deficiency anemia among the iron-takers remained
      0% and the incidence of latent iron deficiency among the iron-takers decreased
      from 12% to 6%.

PMID- 8551684
TI  - [42nd meeting of the Japanese Society of Clinical Pathology. Utsunomia City,
      Japan. October 16-18, 1995. Abstracts].

PMID- 8551683
TI  - [Hand-mirror cells acute lymphoblastic leukemia (L3)].
AB  - To our knowledge, this report represents the first confirmed case in Japan of a
      15-year-old boy with acute lymphoblastic leukemia (ALL).L3 with hand-mirror cells
      (HMC) in the bone marrow. HMC lymphoid leukemia is an unusual variant of ALL in
      which the bone marrow lymphoblasts manifest distinctive hand-mirror morphologic
      features. HMC lymphoblast is characterized by an asymmetric foot-like cytoplasmic
      process that extends from the portion of the cell, thus giving it the light
      microscopic appearance responsible for its name. Besides ALL, HMC has been
      reported in acute myeloblastic leukemia (AML), blastic crisis of chronic
      myelogenous leukemia, non-Hodgkin's lymphoma, and infectious mononucleosis. HMC
      has been reported to be prevalent in ALL.L1 and L2 as compared with L3.

PMID- 8551685
TI  - [Clinical and physiological studies on senile tremor].
AB  - We examined 6 male and 10 female patients with senile tremor which started at 60
      years of age or older. The patients' age on examination ranged from 66 to 82
      years (mean: 73.4; SD: 5.4 years). The surface electromyogram (EMG) was recorded
      from the bilateral biceps brachii, triceps brachii, forearm flexor and forearm
      extensor muscles. The frequency of the tremor was counted and patterns of
      grouping discharges were analysed. The effect of mechanical perturbation to the
      affected muscle on tremor rhythm was also examined. The same investigations were
      performed in 15 male and 7 female patients with essential tremor with onset age
      before 60 years as control patients. The mean frequency was 6.2 Hz (SD: 1.3 Hz)
      in senile tremor and 7.3 Hz (SD: 1.5 Hz) in essential tremor. There was a
      significant difference between the two groups. The mean frequency in control
      patients whose age on examination was 60 years or over was, however, 6.0 Hz (SD:
      0.8 Hz), and there was no difference from the mean frequency in senile tremor.
      The frequency in both groups was inversely correlated to the patient's age on
      examination. The antagonist muscles were reciprocally discharged in 15 patients
      in the senile tremor group and in 7 in the controls. Mechanical perturbation of
      the affected muscle re-set the tremor rhythm in all patients examined. Thus,
      senile tremor had characteristics resembling tremor in the control patients,
      suggesting that senile tremor may be a subtype of essential tremor.

PMID- 8551686
TI  - [Visual event-related potentials and reaction time in Parkinson's disease].
AB  - Visual event-related potentials (ERPs) and reaction times in 29 patients with
      nondemented Parkinson's disease and 19 age-equivalent normal control subjects
      were measured during the physical and semantic discrimination tasks. The
      components of the NA, N2 and P3 and simple and choice reaction times were
      observed in both kinds of discrimination tasks. There were no significant
      differences in either the latency or amplitude of the ERP components (NA, N2 and
      P3) between the Parkinson's disease patients and normal subjects during the
      physical discrimination tasks, but the patients had significantly prolonged
      choice reaction time compared with the normal controls. During the semantic
      discrimination tasks, the N2 and P3 latencies and choice reaction time in
      patients with Parkinson's disease were significantly longer than those of the
      normal controls, although there were no differences in NA latency between the two
      groups. There were no significant differences in any of the amplitudes between
      these groups. These results suggest that motor preparation is delayed in patients
      with nondemented Parkinson's disease, although the stimulus evaluation process is
      largely preserved during the physical discrimination tasks. The results obtained
      from the semantic discrimination tasks are interpreted as electrophysiological
      signs of disturbance in stimulus classification and attention process in
      Parkinson's disease. From the automatic/controlled processes, the present results
      suggest that the automatic processing stage associated with NA may be less
      impaired than the attention-controlled processing reflected by N2 in patients
      with Parkinson's disease.

PMID- 8551687
TI  - [Osteoporosis and fractures in Parkinson's disease].
AB  - We investigated osteoporosis and fractures in Parkinson's disease in stage II to
      V according to Hoehn and Yahr's disability scale. The bone mineral density (BMD)
      of the lumbar spine was measured in 82 patients (24 males and 58 females) and in
      99 age-matched controls (28 males and 71 females) using dual energy X-ray
      absorptiometry, and compression fractures of the vertebrae were assessed on X-ray
      films. BMD decreased with age in females and was lower in females 60 years of age
      or over than in males at the same age. BMD in the female patients was
      significantly lower than in the female controls. The female patients in stage III
      to V had lower BMD than those in stage II. Both male and female patients with a
      body mass index (BMI) below 21 showed a lower BMD than those with a BMI of 21 or
      more. Five male (20.8%) and 37 female (63.8%) patients were diagnosed as
      osteoporosis. In particular 77.8% of the females aged 60 years or older had
      osteoporosis. Thirty-three patients (7 males and 26 females) had experienced
      fractures or were found to have vertebral compression fractures on X-ray films.
      These results suggested that osteoporosis and fractures are common in female
      patients with Parkinson's disease and that prevention of fractures must be
      important especially for patients with osteoporosis.

PMID- 8551688
TI  - [Clinical features of acute pulmonary embolism in the elderly].
AB  - The clinical features of acute pulmonary embolism were evaluated and compared
      between Group A with 38 cases > 65 years old and Group B with 73 cases < 65 years
      old. The mortality rate was 58% (22/38) in Group A and 23% (17/73) in Group B (p
      < 0.01). However the size of the obstructive pulmonary vascular bed showed no
      significant difference in both groups. In group A dyspnea was the most common
      symptom in 27 of 31 (87%), in comparison with group B [45 of 66 (68%), p < 0.05].
      In group B, dyspnea and other symptoms appeared abruptly in 44 of 57 (77%),
      compared with 19 of 36 (53%) in group A (p < 0.02). ECG abnormalities including
      tachycardia, right bundle branch block and clockwise rotation as well as
      hypoxemia were present more predominantly in group A. The presentation of
      pulmonary embolism is variable in the elderly, as in any age group. Many autopsy
      studies showed a significant rise in incidence of pulmonary embolism in higher
      age groups. We must keep in mind the characteristics of clinical features in
      pulmonary embolism in the elderly.

PMID- 8551689
TI  - [Case-card survey on hypotensive treatment in elderly in three different types of
      medical facilities].
AB  - A case-card survey was carried out to understand trends of hypotensive treatment
      in elderly in comparison with non-elderly subjects. Data were obtained from 2,897
      cases including 1,422 elderly (> or = 65 years old) and 1,475 non-elderly
      hypertensives (< 65 years old) collected from Sapporo Medical University Hospital
      and related medical facilities. In the total group of 2,879 cases, frequencies of
      use of hypotensive drugs were as follows: Ca antagonists, 76.3%, beta-blockers,
      31.4%; ACE-inhibitors, 25.1%; diuretics, 18.1; alpha 1-blockers, 10.5%; potassium
      sparing diuretics, 8.8%. In the elderly group, beta-blockers and ACE-inhibitors
      were used less frequently than in non-elderly hypertensives. On the contrary,
      diuretics were administered more frequently in elderly than in non-elderly
      subjects. Comparing the usage of hypotonics among different types of medical
      facilities, higher frequencies of use of beta-blockers and diuretics were
      observed in the university hospital than in general hospitals and private
      hospitals or clinics. ACE-inhibitors were used less frequently in private
      facilities than in the university hospital and general hospital. In summary, Ca
      antagonists were used most frequently in both non-elderly and elderly subjects,
      and in all three different types of medical facilities. Other hypotonics were
      used differently according to patients age. There was differences in the usage of
      drugs apart from Ca antagonists among the three different types of medical
      facilities.

PMID- 8551690
TI  - [Epidemiological study of the prognosis and relevant factors of demented
      patients].
AB  - One hundred twenty patients diagnosed as having dementia at the Center for
      Elderly Dementia in Hyogo College of Medicine, were recruited for this study to
      investigate the factors related to the prognosis of dementia. Patients were
      classified into the following two groups: those staying at home (group 1); those
      who died at home (group 2). The proportion of various dementias was almost equal
      in each group: vascular dementia, 30%; senile dementia of Alzheimer's type, 40%;
      mixed dementia, 20%; Alzheimer's disease, 10%. The average duration of disease in
      the two groups were not significantly different. The average age of onset in
      group 2 was higher than that in group 1. The rate of those with severe dementia
      was higher in group 2 than group 1. Those in group 2 scored less on the Mini
      Mental State examination than those in group 1. Symptoms of dementia were
      assessed by the modified GBS-scale. In group 2, patients scored higher in
      impaired intellectual and motor functions. The CT findings suggested cortical
      atrophy, ventricular enlargement and periventricular lucency more often in group
      2 than in group 1. Laboratory findings revealed that decrease in red blood cell
      count, hemoglobin, hematocrit and serum protein were more apparent in group 2
      than group 1. It was considered that impaired motor functions, cortical atrophy,
      white matter lesions, anemia and malnutrition enhanced the probability of death.
      The study has confirmed that the prognosis of dementia is not only related to
      intellectual impairment but also deteriorated physical conditions such as motor
      dysfunction, anemia and malnutrition.

PMID- 8551691
TI  - [Changes in the level of endothelin-1 with aging].
AB  - Endothelin-1 (ET-1) is a potent and long-lasting vasoconstrictor peptide. In
      order to clarify the changes in the level of ET-1 with aging, we measured the ET
      1 level in plasma by radioimmunoassay and used 74 healthy subjects including 61
      males and 13 females, aged from 30 to 69, who were admitted in the health check
      center of Ashikaga Red Cross Hospital. None of them had risk factors related to
      hypertension, obesity, diabetes mellitus or cardiovascular disease. In the male
      group, the relationship between the level of ET-1 (Y) and age (X) was obtained as
      follows: Y = 0.08857 X +0.06363. The correlation between them was significant
      (gamma = 0.65894, p < 0.05). In the female group also, the increased level of ET
      1 (Y) with age (X) showed an excellent linear relationship (Y = 0.163091 X -4.23,
      gamma = 0.762, p < 0.002). These studies demonstrated that the level of ET-1
      increased in relation to aging and the increased ET-1 production with aging may
      be consistent with deterioration of endothelial function.

PMID- 8551693
TI  - [37th Annual meeting of the Japan Geriatrics Society. Osaka, Japan. October 18
      20, 1995. Abstracts].

PMID- 8551692
TI  - [A case of pulmonary infiltration with eosinophilia (PIE) syndrome associated
      with syndrome of inappropriate secretion of ADH (SIADH) in the elderly patient].
AB  - A 76-year-old woman was admitted to our hospital because of productive cough,
      fever and anorexia in January 1995. She had suffered from bronchial asthma for 25
      years. From 1983, exacerbation of PIE was recorded three times, on which
      occasions prednisolone and antibiotics were quite effective. On admission, marked
      leukocytosis (28,000/microliters) and eosinophilia (18,000/microliters) were
      found. However, plasma IgE level was normal, and specific antigen for
      eosinophilia was not detected by RAST or the skin allergic reaction test. Chest X
      ray film and CT scan revealed extensive bilateral pulmonary infiltration.
      Increase in eosinophils (33%) was demonstrated in bronchoalveolar lavage.
      Furthermore, biopsy specimen of the affected lung revealed diffuse infiltration
      of eosinophils into alveolar septa. On the basis of these findings, the patient
      was diagnosed as chronic eosinophilic pneumonia (PIE syndrome). Hyponatremia (117
      mEq/l) was persistent after the hydration with normal saline. Plasma ADH was not
      suppressed (2.29 pg/ml) in spite of hypoosmolality of plasma. Laboratory
      examination showed that renal, adrenal and thyroid function as well as plasma
      renin activity were normal. Taking these findings together, she was diagnosed as
      having SIADH. Treatment with prednisolone improved not only the PIE syndrome but
      also SIADH.

PMID- 8551694
TI  - [HLA-DQB2 genotypes analyzed by PCR/SSCP method].
AB  - When the PCR products amplified by the primers prepared at the 11th HLA Workshop
      (DQBAMP-A, DQBAMP-B) were analyzed directly by the SSCP method, one or two pairs
      of characteristic bands were detected other than those attributed to DQB1, and a
      total of three kind of paired bands were detected. To confirm that these bands
      were allelic genes of DQB2, the corresponding bands were isolated by cloning, and
      their base sequences were determined. The base sequence of one of them was in
      agreement with that of DX beta, which has already been described, and the
      characteristic 3-base defect was noted by comparison with the base sequence of
      DQB1. The same 3-base defect was noted also in the other two kinds. One-base
      substitution was present in each of the three kinds of base sequence, and they
      were confirmed to be allelic genes of DQB2. In DQB1 typing by the PCR/SSCP method
      of Carrington et al., treatment with the restriction enzyme Alu 1 is needed to
      eliminate DQB2. However, the use of this enzyme was theoretically demonstrated to
      be inappropriate, because it degraded the DQB1*0401 gene.

PMID- 8551695
TI  - Characterization of the 84-kDa protein with ABH activity in human seminal plasma.
AB  - In order to identify the blood group substance detected on the sperm plasma
      membrane (SPM), a plasma membrane preparation was obtained from the sperm soluble
      protein and then injected into a rabbit to produce an anti-SPM antibody. An anti
      SPM antibody-binding affinity column specifically bound 6 polypeptides with
      molecular masses of 135 kDa, 84 kDa, 78 kDa, 67 kDa, 54 kDa and 20 kDa from
      seminal plasma. Among these polypeptides, the 84-kDa protein (p 84) showed ABH
      antigenic activity upon immunoblotting. When viable, motile sperm were incubated
      at 37 degrees C in the culture medium, they became capacitated and p 84 was
      released into the medium from the sperm surface after 3 h of incubation,
      indicating that p 84 is a sperm-coating antigen. Immunoblotting of sexual glands
      revealed that this protein is originated from the seminal vesicle. Its
      immunological properties were similar to those of lactoferrin. When seminal
      plasma was immunoprecipitated with anti-human lactoferrin antiserum, the
      immunoprecipitates contained both p 84 and ABH antigenic activity. The amino acid
      sequence of the N-terminus of p 84 was determined to be: G-R-?-R-?-S-V-Q-W-?-A-V
      S-Q-P-E-A-D-K-?-F-Q-W-Q-R-N-M-R-K-V-R-G-P-?-V or P-S?-?-I. Although this sequence
      is highly homologous to lactoferrin, the 18th residue is different (p 84, D;
      lactoferrin, T). These data suggest that p 84 is the protein which has not been
      identified and bears the ABH antigen. A sandwich ELISA using anti-SPM antibody
      was able to bind p 84 and allowed determination of the ABO blood type of semen
      and saliva, but detected no ABH antigenic activity in breast milk, vaginal fluid,
      erythrocytes, serum or urine. These results suggest that p 84 is the best
      candidate for ABO blood typing of semen when contaminating vaginal fluid is
      present.

PMID- 8551696
TI  - Estimation of age from soft X-ray findings of Japanese pubic symphysis based on a
      image processing.
AB  - A method for estimating the age at death through the image processing of soft X
      ray pictures of pubic symphysis is reported. The collected 533 materials were
      sliced at the thickness of 5 mm. Prior to the image processing, subjective
      assessment was made on the five indices of gross morphological findings. The
      pictures showed roughening and darkening tendencies with age and two indices for
      image processing were introduced. Applying the natural logarithm to data obtained
      by the image processing and making regression analysis. two kinds of age
      estimation equations were derived in the form of; Y = -39.91 lnX + 189.63 and the
      estimated age Y was proportional to natural logarithm of measured indices X. The
      age estimation equations showed accuracies of 70% or more for the age range of +/
      5 years and 100% for +/- 8 years. The accuracy was satisfactory for age
      estimation in the field of person appraisal in legal medicine.

PMID- 8551697
TI  - PCR amplification of D2S44 (YNH24) alleles.
AB  - We have successfully amplified D2S44 (YNH24) alleles by a method for long
      distance PCR using a special polymerase enhancer, Taq Extender PCR Additive. The
      alleles amplified from DNA samples of 58 Japanese subjects ranged from 0.42 to
      3.5 kb and were 1.5 kb shorter than those detected by Southern blotting of Hinf I
      digested genomic DNAs. Although alleles longer than 3 kb were barely visible by
      ethidium bromide staining, we were able to visualize them clearly with SYBR GREEN
      I NUCLEIC ACIC GEL STAIN. PCR amplification of D2S44 alleles is much simpler than
      their restriction fragment length polymorphism (RFLP) analysis; therefore, our
      procedure is well-suited for use in medicolegal practice. With minor
      modifications, the method described here should be applicable to other loci of
      variable number of tandem repeats (VNTRs) that have been analyzed by Southern
      blotting.

PMID- 8551698
TI  - [An autopsy case of a pacemaker implanted patient].
AB  - A pacemaker implanted patient (female, 78 years old) was found dead in her bed
      and judicially autopsied. Before postmortem inspection the pacemaker was removed
      by a doctor. We report the problems in such as the doctor's treatment,
      additionally accommodation of medical examiners and police, and determination of
      a cause of death in autopsy.

PMID- 8551699
TI  - Identification of human skeletal remains with a mandibular static bone cavity by
      comparison between ante- and post-mortem dental orthopantomograms: a case report.
AB  - We report a case of human skeletal remains in which a mandibular static bone
      cavity noted in a dental orthopantomogram assisted the positive identification.
      Unknown totally skeletonized human remains were found on a bushy slope of a hill.
      In the pockets of the clothing, there were a wooden seal, on which a family name
      was inscribed, and two cigarette lighters bearing the name of a bank. The body
      was identified as a male, about 50 years old. The estimated time elapsed since
      death was about six months to one year. No evidence of trauma was found in the
      clothing and the bones. The possible cause of death was due to poisoning from
      ingestion of bromvalerylurea (hypnotics). From the family name inscribed on the
      seal and the name of a bank on the cigarette lighters, the police investigation
      caught a missing man of 46 years old, who had last been seen alive about 6 months
      before. A dental orthopantomogram taken about 2 years before his disappearance
      was available for comparison. Eighteen days after recovery positive
      identification was practically accomplished based on unique features of the
      dental findings and a fairly rare, mandibular static bone cavity (a kind of bone
      cysts) by a X-ray comparison.

PMID- 8551700
TI  - [38th Annual meeting of the Japanese Society of Nephrology. Tokyo, Japan.
      November 26-28, 1995. Abstracts].

PMID- 8551701
TI  - [Role of glycosaminoglycans relating to formation of urolithiasis].

PMID- 8551702
TI  - [A single session of transurethral balloon laser thermotherapy for benign
      prostatic hyperplasia].
AB  - BACKGROUND: The objective of this study is to evaluate the efficiency of a new
      method of transurethral balloon laser thermotherapy (TUBAL-T) using prostalase in
      patients with benign prostatic hyperplasia. METHODS: From September 1993 to March
      1994, 21 men were treated with a single session of TUBAL-T for the relief of
      bladder outlet obstruction secondary to benign prostatic hyperplasia. Thirteen of
      them had hormonal therapy before TUBAL-T and have no mediation after treatment
      (group A). Eight men had no hormonal therapy before and after TUBAL-T (group B).
      The clinical efficacy of this modality was evaluated by analysing the subjective
      and objective responses following the treatment. The laser balloon, equipped with
      a cooling system for preservation of urethral mucosa, delivers a Nd:YAG laser
      into the prostate. Treatment was performed by using a laser powder of 30 to 50
      watts for 40 minutes. At 3 months after treatment, the clinical efficacy was
      evaluated by subjective symptom score, and residual urine volume, uroflowmetry
      and prostatic volume by transrectal ultrasound as objective data. RESULTS: In
      group A, subjective symptom scores decreased by an average of 72.8%, the average
      uroflow rates and the peak uroflow rates increased by an average of 44% and
      45.9%, the post-void residual urine volume rates decreased by an average of 58.4%
      and ultrasonography showed that the prostatic volume decreased in 8 men but
      increased in 5 men. In group B, symptom score decreased by an average of 85.1%,
      the average uroflow rates and the peak uroflow rates increased by an average of
      46.2%, the post-void residual urine volume rates decreased by average of 83.4%
      and ultrasonography showed that the prostatic volume decreased by an average of
      35.6%. CONCLUSION: During the treatment and follow-up period, no adverse effect
      was detected. These results suggest that TUBAL-T for the relief of bladder outlet
      obstruction secondary to BPH is a useful therapy.

PMID- 8551703
TI  - [Assessment of separate renal function with Doppler ultrasound measurement].
AB  - BACKGROUND: To evaluate measurement of separate renal function with Doppler
      ultrasound, renal blood flow velocity of interlobar and segmental arteries was
      examined with color Doppler echography. METHODS: Maximum blood flow velocity,
      minimum blood flow velocity, mean blood flow velocity, acceleration, resistive
      index, and pulsatility index were used as parameters of blood flow. RESULTS: In
      71 patients who had undergone unilateral nephrectomy (group 1), interlobar
      arterial minimal blood flow velocity correlated with creatinine clearance (r =
      0.59) and 15 min. PSP value (r = 0.47). In 43 patients whose separate renal
      functions were different each other (group 2), the separate Ccr calculated from
      radioisotope renogram, correlated with interlobar arterial minimal blood flow
      velocity (r = 0.75). As far as unilateral renal blood flow velocity showed the
      same value, Ccr in group 1 was larger than in one kidney of group 2. This would
      be account for the fact that the volume of unilateral renal parenchyma which was
      measured by CT scan was larger in group 1 than in one kidney of group 2. In
      addition, the left to right ratio of Ccr was similar to that of interlobar
      arterial minimal blood flow velocity. Interlobar arterial minimal blood flow
      velocity has been decreasing along with aging in cases with normal kidneys.
      CONCLUSION: Color Doppler echography is a useful technique for estimating
      separate renal function.

PMID- 8551704
TI  - [Laparoscopic radical nephrectomy. Analysis of 10 cases and preliminary report of
      retroperitoneal approach].
AB  - PURPOSE: To examine the efficacy of laparoscopic radical nephrectomy (LPRNX) for
      patients with small renal cell carcinoma, the clinical result of 10 patients
      treated with this procedure was analysed. MATERIALS: Ten patients with renal cell
      carcinoma measuring diameter less than 5 cm were treated by LPRNX between July
      1992 and October 1994. Four cases had T1N0M0 disease and 6 had T2N0M0 disease. Of
      the 10 patients, seven had right sided tumor and three had left sided tumor.
      METHOD: Trans-abdominal approach was employed for the initial 8 cases.
      Retroperitoneal approach was applied for the last 2 cases. Five trocars were
      placed through lateral abdominal wall. Intraperitoneal or retroperitoneal cavity
      was insffulated with CO2 at 12 mmHg. A kidney was dissected endoscopically with
      Gerota's fascia, peri renal fatty tissue and adrenal gland as en bloc fashion. It
      was trapped into the laparoscopy sack and pulled out of the body through a 4 to 5
      cm incision without morcellation. RESULTS: Average operation time was 331 minutes
      and average bleeding was 380 ml. All the kidneys were removed by endoscopic
      technique. As major complications, we experienced a cases of splenic injury and a
      cases of adrenal injury. The bleeding of both cases was successfully managed by
      endoscopical procedure, however, transfusion was needed for the last case.
      Pathological examination of specimens revealed renal cell carcinoma in all ten
      cases. Average hospital stay after surgery was 10.6 days and average duration to
      the convalescence was 20 days. There was no episode of recurrence in all 10
      patients for 2 to 29 months (Mean: 15.2 months) followed up period. CONCLUSION:
      Although further technical progress was expected, LPRNX is a potential operative
      procedure that realizes minimally invasive therapy for the patients with small
      volume of renal cell carcinoma.

PMID- 8551705
TI  - [Transrectal ultrasound guided biopsies in 266 patients].
AB  - BACKGROUND: The objective of this study is to evaluate the diagnostic utility of
      digital rectal examination (DRE), prostate specific antigen (PSA) and transrectal
      ultrasonography (TRUS) for prostate cancer. METHODS: On 266 patients
      ultrasonography guided transrectal biopsies were performed using the automatic
      biopsy gun fitted with an 18 gauge biopsy needle. RESULTS: There was no major
      complication. Cancers were found in 52 patients (19.5%), and 16 of them were not
      identified by echography. Among 67 hypoechoic areas detected by echography, 36
      (53.7%) were found to be cancer. The positive predictive value of DRE was 52.1%
      and that of PSA and TRUS were 24.4% and 53.7%, especially the rate increased to
      93.7% by combining of these three techniques. CONCLUSION: These results suggest
      that the use of DRE, PSA in conjunction with TRUS enhances early detection of
      prostate cancer.

PMID- 8551706
TI  - [Use of semirigid ureteroscopes for treatment of ureteral calculi].
AB  - BACKGROUND: The objective of this study is to evaluate the efficacy of
      ureteroscopic lithotripsy as the treatment of ureteral stones in the recent era
      by comparing the result using a semirigid ureteroscope with the result using a
      conventional ureteroscope. METHODS: Between 1991 and 1994, 136 patients with
      ureteral calculi underwent transurethral ureteroscopic lithotripsy in our
      hospital. From July 1991 to March 1993, 14F rigid ureteroscope with the rod lens
      system was used for 82 patients (group 1), whereas from April 1993 to July 1994
      either a 9.5F or 7F semirigid fiberoptic ureteroscope was used for 54 patients
      (group 2). Insertion of ureteroscopes was performed under continuous irrigation
      of saline without mechanical dilation of the ureteral orifice in both groups.
      RESULTS: The rates of complete removal of stone at the first trial were 56.1% in
      group 1 and 72.2% in group 2 with the overall complete removal rate of 62.5%. The
      complete removal rates of stones in the upper, middle and lower ureters were
      18.2%, 54.8% and 72.4% in group 1 and 14.3%, 72.7% and 88.0% in group 2,
      respectively. The major reasons for unsuccessful treatments was upward migration
      of stones during the procedure. As intraoperative complications, ureteral
      disruption occurred in 1 case in group 1, and ureteral perforation in 5 patients
      in group 1 (6.1%) and 2 in group 2 (3.8%). Acute bacterial infection with
      prolonged fever was observed in 3 patients in group 1 and in none in group 2.
      CONCLUSION: From these results, the new semirigid ureteroscope with fiberoptic
      imaging bundles made the transurethral lithotripsy a safer and more efficient
      procedure for the treatment of ureteral calculi especially those in the lower
      ureters.

PMID- 8551707
TI  - [Clinicopathological study of incidental renal cell carcinoma].
AB  - BACKGROUND: The objective of this study is to evaluate the clinicopathological
      features of incidental renal cell carcinoma, compared with non-incidental
      carcinoma. METHODS: Between July 1st, 1984 and June 30, 1994, 87 renal cell
      carcinoma patients were treated at our hospital; 56 had non-incidental renal cell
      carcinoma and 31 had incidental carcinoma. The clinicopathological features were
      examined. RESULTS: The incidence of incidental cancer ranges from 0 to 66%, and
      the incidence has increased in recent years. The median value of maximal tumor
      size was 4.0cm (1.5 approximately 8.0cm) for incidental cancer, and 8.0cm (3.0
      approximately 16cm) for incidental cancer, and 8.0cm (3.0 approximately 16cm) for
      non-incidental cancer, i.e., the incidental cancer was significantly smaller than
      the non-incidental one (p < 0.001). The pathological stage of the resected non
      incidental renal cell carcinoma (n = 47) was pT1, pT2, pT3 and pT4 in 0, 23, 21
      and 3 patients, respectively. For the resected incidental renal cell carcinoma (n
      = 31) 3, 26, 2 and 0 patients showed pathological stages pT1, pT2, pT3 and pT4,
      respectively; the pathological stage of incidental renal cell carcinoma was
      significantly lower than that of non-incidental carcinoma (p < 0.001). Eighteen
      and 29 resected non-incidental renal cell carcinoma were grades 1 and 2,
      respectively, whereas 17 and 14 resected incidental renal cell carcinomas were in
      grades 1 and 2, respectively. Vascular invasion by tumor cells was shown in 31
      (66.0%) and 8 (25.8%) patients with non-incidental and incidental renal cell
      carcinomas, respectively; the incidence of vascular invasion in incidental cancer
      being significantly lower than in non-incidental cancer (p < 0.001). The
      performance status and general condition in patients with incidental renal cell
      carcinoma were superior to those in patients with the non-incidental cancer. The
      1, 3 and 5-year survival rate of all 87 renal cell carcinoma patients was 81, 62
      and 57%, respectively. These rates for patients with non-incidental renal cell
      carcinoma were 72, 48 and 41%, respectively, and those for incidental cancer
      patients were 100%. The survival of patients with incidental renal cell carcinoma
      was significantly better than that of non-incidental carcinoma patients (p <
      0.005). CONCLUSION: Our results suggest that the detection of incidental renal
      cell carcinoma will increase, and that the prognosis for renal cell carcinoma
      will improve. However, even in incidental renal cell carcinoma, careful long-term
      follow up may be necessary, since some tumors are comparatively large and exhibit
      vascular invasion.

PMID- 8551708
TI  - [Participation of atrial natriuretic peptide (hANP) levels and arginine
      vasopressin (AVP) in aged persons with nocturia].
AB  - BACKGROUND: The associations of human atrial natriuretic peptide (hANP) and
      arginine vasopressin (AVP) with nocturia in two groups of elderly individuals
      were investigated. METHODS: Plasma hANP and AVP levels were determined at 8:00,
      14:00, 20:00, 2:00 and 8:00 (2nd day) in 15 healthy younger elderly individuals
      and 30 elderly individuals who showed no abnormal physical findings. Urine
      volume, urinary Na and K levels, and urinary osomotic pressure were also
      determined every 6 hours at the above-mentioned times. The maximum diameter of
      the inferior vena cava (IVC) in the inferior portion of the confluence of the
      hepatic veins was determined at 14:00, 20:00 and 2:00 in 11 younger elderly
      individuals and 17 elderly individuals. RESULTS: The mean hANP level was
      significantly higher in the elderly group than in the younger elderly group, and
      the mean AVP level was significantly higher in the younger elderly group than in
      the elderly group. There were no significant differences in diurnal variation in
      hANP between daytime and night among the younger elderly individuals, but the
      hANP level was significantly increased during the night in the elderly
      individuals. The AVP level was significantly higher at night than during the
      daytime in the younger elderly individuals, while it was significantly decreased
      at night in the elderly individuals. Although there was no marked diurnal
      variation in the IVC in any of the younger elderly individuals, IVC diameter was
      significantly increased at night in the elderly individuals. Urine volume was
      high during the daytime in the younger elderly group, and increased during the
      night in the elderly group. CONCLUSIONS: The increase in body fluid and elevation
      of hANP over the time between evening and night, and the decrease in AVP
      accompanying these increases were considered to lead to the increase in urine
      volume during the night, and this increase is considered to be a factor in
      nocturia.

PMID- 8551709
TI  - [Effects of castration on apoptosis and transforming growth factor-beta 1 mRNA in
      the neonatal mouse seminal vesicles].
AB  - BACKGROUND: In the adult male rat prostate, castration induces apoptosis of
      epithelial cells concomitant with the increase in transforming growth factor-beta
      1 (TGF-beta 1). In the present study, we investigated the effects of castration
      on apoptosis and TGF-beta 1 mRNA in neonatal mouse seminal vesicles. METHODS: 5
      day-old BALB/c mice were castrated by Pfeifer's method. We estimated the weight,
      3H-thymidine uptake by whole seminal vesicles, the amount of TGF-beta 1 mRNA by
      RT-PCR method, and the apoptotic index of both epithelium and mesenchyme.
      RESULTS: The castration of 5-day-old neonatal mice resulted in much less weight
      of seminal vesicles and DNA synthesis estimated by 3H-thymidine uptake by whole
      seminal vesicles compared to intact neonatal mice, indicating that the growth of
      neonatal mouse seminal vesicles depends on androgens secreted by the testis. The
      amount of TGF-beta 1 mRNA estimated by RT-PCR method increased 4 days after
      castration at 5 days of age. However, the castration did not induce apoptosis in
      the seminal vesicles. CONCLUSION: The present study indicates that castration of
      neonatal mice does not induce apoptosis in the seminal vesicles, although it does
      a transient increase in TGF-beta 1 mRNA in the seminal vesicles.

PMID- 8551710
TI  - [Effects of androgen regulation system on bladder carcinogenesis in male mice].
AB  - PURPOSE: In several previous reports, it has been suggested that the androgen
      system is related to bladder carcinogenesis. In this study, to understand the
      mechanism underlying this relationship, we administered a LH-RH agonist depot
      (Leuprolide depot), a pure-antiandrogen (flutamide) or a 5 alpha-reductase
      inhibitor (finasteride) to the mice in the promotion state of bladder
      carcinogenesis by N-butul-N-(4-hydroxybutyl) nitrosamine (BBN). MATERIALS AND
      METHODS: 177 C3H/He male mice were divided into 7 groups. All mice were treated
      with 0.05% BBN for 10 weeks and were maintained over the subsequent 12 weeks with
      the following treatments. Group 1 was a control group; in group 2, castration was
      performed at the 11th week; in group 3, finasteride was administered starting the
      11th week; in group 4, a LH-RH agonist depot was administered starting the 11th
      week; in group 5, flutamide was administered starting the 11th week; in group 6,
      both finasteride and a LH-RH agonist depot were administered simultaneously
      starting the 11th week; and in group 7, both flutamide and a LH-RH agonist depot
      were administered simultaneously starting the 11th week. RESULTS AND CONCLUSIONS:
      (1) We confirmed that castration significantly suppressed bladder carcinogenesis.
      (2) Finasteride or flutamide administration as monotherapy had no effect on the
      results; however, the dosages of these drugs may have been too low, so we are
      planning a study with higher doses. (3) Conversely, the LH-RH agonist depot
      significantly promoted bladder carcinogenesis, we believe that the high levels of
      testosterone immediately after the administration were responsible for this
      promotion. (4) Simultaneous administration of flutamide suppressed this LH-RH
      induced promotion of carcinogenesis.

PMID- 8551711
TI  - [Characterization of prostate cancer, benign prostatic hyperplasia and normal
      prostates using endorectal 1H magnetic resonance spectroscopy].
AB  - BACKGROUND: We evaluate the usefulness of 1H endorectal resonance spectroscopy to
      characterize prostate pathology. METHODS: With an endorectal surface coil we have
      studied 20 individuals with normal (1), benign hyperplastic (9) and malignant
      (10) prostates. RESULTS: The major findings of our studies were that the patients
      with cancer have a significantly lower citrate-to-choline ratio (cit/cho) and
      creatin-to-choline ratio (cre/cho) than the patients with BPH (p < 0.05). There
      is well correlation between cit/cho and gland-to-stroma ratio of the BPH tissue
      as well as histological grade of the cancer tissue. 1H spectroscopy offers the
      advantages of differential diagnosis between benign and malignant prostates. We,
      however, failed to demonstrate cancer in 2 cases; the lesion was too small in one
      case, and out of the region of interest in the other. It is necessary that the
      foci in the prostate is at least 1.5 X 1.5 X 1.5 cm3 of the volume in order to
      obtain genuine spectrogram of carcinoma. CONCLUSION: Endorectal 1H magnetic
      resonance spectroscopy can characterize metabolic differences between the normal
      and malignant prostate.

PMID- 8551712
TI  - [Bladder cancer in spinal cord injury patient. A case report].
AB  - A case of bladder cancer following spinal cord injury is reported. A 57-year-old
      male with L1 incomplete paraplegia was referred to our hospital under the
      diagnosis of bladder tumor with gross hematuria in November, 1994. Radical
      cystectomy, rt nephroureterectomy (nonfunctioning kidney) and lt
      ureterocutaneostomy were carried. Histopathological study revealed squamous cell
      carcinoma (well differentiation) and transitional cell carcinoma (G3), stage
      pT3b. He has been doing well without recurrence for 4 months after operation.

PMID- 8551714
TI  - [Mechanism of bacterial regrowth at the sites of infection in Mycobacterium avium
      complex-infected mice during treatment with chemotherapeutic agents].
AB  - Although various antimicrobial drugs show appreciable bactericidal activity in
      the early phase (2 to 4 weeks after infection) of Mycobacterium avium complex
      (MAC) infections in mice, no drug, as far as we know, can continue to exert the
      growth inhibiting activity against the bacteria at the site of infection in the
      progressed stage. Here, we studied the mechanisms of the bacterial regrowth which
      usually starts around 2-4 weeks after infection. First, the changes in the level
      of TNF-alpha, IFN-gamma, IL-6 and IL-10 in the lungs and spleen during the course
      of MAC infections was examined. Tissue levels of TNF-alpha and IL-10 increased
      around weeks 2 to 4, then rapidly decreased thereafter, and returned to the
      normal levels by week 8, while levels of IFN-gamma and IL-6 remained very low
      throughout the observation period. In this experiment, the bacterial CFUs rapidly
      decreased during the first 2 weeks of the treatment with a rifamycin derivative,
      KRM-1648, and thereafter the regrowth of the organisms was observed even in mice
      treated continuously with KRM-1648, although the rate of bacterial growth in the
      treated mice was much lower than in untreated control mice. Second, effect of
      either anti-TGF-beta or anti-IL-10 antibody on intracellular growth of MAC in
      human monocytes cultured in vitro in the medium with or without addition of TNF
      alpha or IFN-gamma were examined. Anti-TGF-beta and anti-IL-10 antibodies
      potently reduced the bacterial growth in monocytes. Effects of TNF-alpha and IFN
      gamma in reducing the bacterial growth was potentiated by the addition of either
      anti-TGF-beta or anti-IL-10 antibody. Third, anti-IL-10 antibody augmented to
      some extent the chemotherapeutic efficacy of KRM-1648 against MAC infection, when
      the drug was given to mice at weeks 2 and 4 after infection. From these results,
      it is suggested that IL-10 derived from MAC-infected macrophages in response to
      stimulation with some bacterial components, such as lipoarabinomannan, might
      downregulate the antimicrobial function of host macrophages against MAC.

PMID- 8551713
TI  - [A case of retroperitoneal dedifferentiated liposarcoma with tumor thrombus in
      the inferior vena cava].
AB  - We experienced a case of retroperitoneal dedifferentiated liposarcoma with tumor
      thrombus in the inferior vena cava. A 45-year-old man was pointed out a
      retroperitoneal mass on ultrasound examination. He was referred to the Department
      of Urology, Tochigi Cancer Center for critical evaluation. Image diagnostic
      procedures showed a retroperitoneal mass surrounded by loose tissue and large
      thrombus in the inferior vena cava. The tumor was removed surgically with right
      lobe of the liver and segment of the inferior vena cava. Histological examination
      revealed the tumor composed of the peripheral well differentiated liposarcoma and
      the central dedifferentiated liposarcoma. Characteristic radiological findings of
      retroperitoneal liposarcoma with dedifferentiation could be pointed out.

PMID- 8551715
TI  - [Comparison of the clinical features of smear-positive and culture-positive
      tuberculous patients with smear-negative and culture-positive patients in an
      education hospital].
AB  - The clinical features of 27 smear-positive and culture-positive tuberculous
      patients (Group 1) were compared with those of 39 smear-negative and culture
      positive patients (Group 2) experienced in our hospital. The proportion of the
      patients who have underlying diseases was lower in Group 1 than Group 2. Ninety
      five % of the patients in Group 1 showed positive PPD skin reaction in comparison
      with 73% of the patients in Group 2. In most of the patients in Group 1, the
      chest X-ray findings were typical ones for pulmonary tuberculosis, but 36% of the
      patients in Group 2 showed atypical X-ray findings. Final diagnosis was more
      difficult for the patients in Group 2 than Group 1. Almost all patients in Group
      1 could be diagnosed within a few days and were referred to a tuberculosis
      hospital for the treatment of tuberculosis. On the contrary, by the patients in
      Group 2, the final diagnosis was delayed more than one month until the results of
      culture was available. Also, many patients in this group had underlying disease
      and only 8 patients could be transferred to a tuberculosis hospital.

PMID- 8551716
TI  - [Studies on the method to quantify PPD and its adsorption onto glass-surface].
AB  - The potency of PPD is very stable when kept as a lyophilized preparation or as a
      solution of high concentrations, but, as is well known, when diluted to the
      practical concentrations such as used in skin-testing for human, its potency
      diminishes rather rapidly. It has been considered that such decrease in potency
      is not due to denaturation of PPD, but due to its adsorption onto the surface of
      glass- or plastic-container. The adsorption of PPD had been studied by several
      authors with radiolabeled PPD or by the potency test in experimental animals or
      human. However, either method is not satisfactory because they are not
      quantitative and reproducible. Consequently, we developed a new method basing on
      ELISA to measure such low concentrations of PPD as used in skin-testing in human.
      Using this new method, we analyzed the adsorption of PPD onto glass-surface. The
      major characteristics of the PPD adsorption revealed by the present studies are
      as follows; (1) The adsorption of PPD takes place very rapidly immediately after
      the distribution of PPD solution to a new container and then proceeds in slower
      rates. (2). The rate of adsorption is influenced by both temperature and
      concentration of PPD solution. The rates of adsorption are almost the same at -80
      degrees C and at 6 degrees C, much higher at 22 degrees C and further higher at
      37 degrees C at any concentration tested. At -80 degrees C and 6 degrees C, there
      is no difference among the adsorption rates at three different concentrations,
      but at 22 degrees C and 37 degrees C, the rate of adsorption at the lowest
      concentration (0.25 microgram/ml) is much higher than those at higher
      concentrations. (3) The amounts of PPD adsorbed are determined by the surface
      area of glass in contact with PPD solution. (4) The larger the volume of PPD
      solution distributed, the bigger the absolute amount of PPD adsorbed, but the
      smaller the rate of adsorption. (5) So-called "volume effects" are evidenced.
      Commercially available Japanese PPD preparations have been produced and adjusted
      their potency taking such adsorption phenomena into consideration. But, if undue
      adsorption is induced by unappropriate handling and/or usage, the potency might
      be diminished. Especially, the single-dose preparation may be affected most
      strongly by so-called "volume-effects". Standard handling and usage recommended
      by the manufacturer are strictly required.

PMID- 8551717
TI  - [Tuberculosis among immigrants in Japan--epidemiological, clinical and
      sociological features, and the future of control].
AB  - Case of tuberculosis among immigrants in Japan have been increasing recently as
      the entry of the foreigners increases. The 1993 national survey showed that the
      number of the newly registered tuberculosis patients among immigrants (new
      comers) was 593 (1.2% of total patients) in 1992. Though their proportion among
      all patients is still yet small, immigrant cases show remarkable disparity in
      geographical and age distribution. Immigrant patients present various challenges
      in the control of tuberculosis, with higher rates of defaulter in treatment and
      drug resistance. This study analysed the characteristics of the problems with
      various data and made recommendations for the future control programme.
      Epidemiologically, the mean tuberculosis incidence during the period from 1987 to
      1992 was estimated for the population of each country of origin. The rate for the
      whole immigrants was between 58.1 and 76.7 per 100,000, which was 2 to 5 times of
      the rate (i.e. 39) for Japan in 1992. The trend of the incidence after the
      arrival in Japan by year cohort was also estimated. It was found that the shorter
      the stay, the higher the incidence. Future estimate of tuberculosis incidence in
      immigrants was made based on the assumptions of the population in and out flows.
      In 2005, the number of new immigrant patients will be between 1169 and 846,
      representing 3.4% to 2.5% of all tuberculosis patients expected a decade hence.
      By reviewing the clinical data and chest radiogrphy of 157 immigrant patients
      currently diagnosed in Tokyo area, the attack timing of the disease for each
      patient was estimated. Nearly half the patients who would be diagnosed later was
      estimated to have some abnormal shadows on chest radiography before arrival in
      Japan, while the other half or at least 30% developed tuberculosis after arrival.
      These indicate the importance and the limitations of screening by chest
      radiography at the early stage of arrival. The clinical status and treatment
      compliance were better among the legal immigrants such as Japanese language
      school students that the over-stay (illegal) immigrants. The extra-pulmonary
      cases consisted only 7% of the total disease, which was similar to the whole
      patients in Japan. The perception and knowledge about tuberculosis and
      tuberculosis services among immigrants was found some different from those among
      Japanese. With the data analysed above and the information on the policy and
      guidelines in other countries, it is recommended that guidelines for improved
      Case-finding and treatment of tuberculosis among immigrants need to be developed
      in Japan, and pilot trials at local level should be instituted. For surveillance
      for tuberculosis in immigrants a standardized information system must be
      developed.

PMID- 8551718
TI  - [Assessing & nursing fetal well-being].

PMID- 8551719
TI  - [Assessment of fetal maturity and genetic disorder].

PMID- 8551720
TI  - [Obstetrical ultrasonography for fetal assessment].

PMID- 8551721
TI  - [A case study of menopausal syndrome].

PMID- 8551722
TI  - [Phenomenological approach to self regulation related to health of patients with
      adult disease].

PMID- 8551723
TI  - [The effects of human potential seminar on the level of self-actualization and
      self-identity in nursing students].

PMID- 8551724
TI  - [A study on improvement of dental health services in school].

PMID- 8551725
TI  - [A study of factors influencing turnover solution in hospital nurses].

PMID- 8551726
TI  - [UN Fourth World Conference on Women].

PMID- 8551728
TI  - [A study for enhancing the image of medical services in a hospital].
AB  - The purpose of this study was to investigate client's satisfaction and to promote
      the image of medical services in the hospital. It is important to identify how
      client is satisfy with the medical services for the image of hospital. The study
      was done on population group of 334 patients and their families who had been
      admitted to the hospital in Seoul from July 15 to July 31, 1995. Data was
      collected by questionnaires on all steps of the research. Subjects were
      instructed to rate the 5 point likert type scale on items. 328 questionnaires
      returned and were used for this analysis. The results were summarised as follows:
      1. The characteristics of the subjects were as follows: the age group of 20-39
      years was 61.0%. For academic background, 51.2% were graduated from high school
      and 28.7% were graduated from College. 2. The average scores for the services
      rendered were as follows: a) Satisfaction on nursing services 3.75 b)
      Satisfaction on kindness of hospital workers 3.55 c) Satisfaction on medical
      services 3.36 d) Satisfaction on environmental elements 3.19 e) Satisfaction on
      diet for the patients 3.18 3. The lowest score of client's satisfaction on each
      area shown in this study is as follows: a) Doctors explain result of tests and
      patient's home management 3.23 b) Nurses are eager to resolve client's problem
      3.47 c) In environmental elements, toilets, room temperature, diet, store 2.81
      2.91.

PMID- 8551727
TI  - [A study on menopausal symptoms and health needs among middle aged women].
AB  - During the middle age of a woman's life cycle, several health changes and
      problems occur. Therefore, middle aged women must manage their health and
      maintain quality life by coping with bodily changes. However, today there is not
      enough research and health programs for middle aged women. Data from the study
      will be used for health promotion program development of middle aged women. Data
      was collected from January 21 to 24, 1995 by telephone interview. Four hundred
      middle aged women between 40 and 59 years old and living in Chon Ju City were
      interviewed. The results of this study were as follow: 1. Frequency rate of
      menopausal symptoms was 38.4%. The most serious menopausal symptom was
      psychosomatic symptom. Mean score orders of experienced symptoms were back pain,
      joint pain (1.80), nervousness (1.80), general weakness (1.67). 2. The most
      important problems as perceived by the clients were children (45.8%), health
      (24.0%) and economics (7.8%). The most serious health problems were concerning
      the muscle-skeletal system (45%) such as arthritis, spinal disk problems and
      osteoporosis. Adult diseases (14.5%) such as hypertension and diabetes were also
      health concerns. Health management activities reported were exercise (22.5%),
      social activity (12%) and inactivity (53%). 33% of clients were interested in
      health groups and they wanted a program of health education, exercise and social
      activity to be provided. 3. General characteristic variables were significantly
      related to the level of menopausal symptoms as follows: age (t = -2.06, p =
      0.040), status of marriage (t = -3.56, p = 0.000), educational level (F = 4.35, p
      = 0.05) and menopausal status (t = 4.37, p = 0.000).

PMID- 8551729
TI  - Clinical significance of cathepsin D assay in breast cancer tissues.
AB  - Cathepsin D was assayed in 74 primary breast cancer specimens by enzyme
      immunoassay (EIA) and immunohistochemical assay (ICA). Of the 74 specimens, 38
      (51.4%) were scored positive by ICA, and 25 (33.8%) were scored positive by EIA.
      The coincidence rate between ICA and EIA was 71.6% (53/74). There was no
      significant correlation between cathepsin D and menopausal status, tumor size,
      number size, number of metastatic lymph nodes, histological type of the tumor, or
      steroid receptor status. Cathepsin D status designated by EIA or ICA predicted
      neither disease-free survival (DFS) nor overall survival (OAS). Subject analysis
      with estrogen receptor, menopausal, and lymph node status revealed no association
      between cathepsin D and DFS or OAS. Therefore, cathepsin D is not an independent
      prognostic factor in breast cancer.

PMID- 8551730
TI  - Prognostic evaluation of lymphadenectomy for epithelial ovarian cancer.
AB  - Between 1989 and 1991, 150 patients with ovarian cancer were treated with
      chemotherapy, including cisplatin, in the Tokai Ovarian Tumor Study Group. Of
      these patients, 25 underwent cytoreductive surgery with lymphadenectomy,
      including removal of either pelvic or para-aortic lymph nodes, and 36 underwent
      both lymphadenectomies. A significant difference was observed between survival
      curves of the groups with positive and negative lymph nodes, respectively (P =
      0.0049). The overall survival was longer in the lymphadenectomy group than in the
      nonlymphadenectomy group (P = 0.0842), and a significantly longer survival time
      was noted for stage III patients who underwent lymphadenectomy compared with
      those who did not (P = 0.0185). Multivariate analysis demonstrated that
      lymphadenectomy is a positive prognostic factor. The authors conclude that both
      pelvic and para-aortic lymph nodes should be resected to improve survival as well
      as to assess exact staging in patients with ovarian cancer.

PMID- 8551731
TI  - Benign salivary gland tumors: a cytogenetic study of 21 cases.
AB  - Cytogenic findings of 21 benign salivary gland tumors, including 14 pleomorphic
      adenomas, 5 Warthin's tumors, 1 myoepithelioma, and 1 cystadenoma, are reported.
      The present study confirms that pleomorphic adenomas characteristically have
      highly specific rearrangements involving only a few chromosome regions (3p21,
      8q12 and 12q13-15) which suggests their specific role in the mixed tumor genesis.
      Warthin's tumors also show non-random numerical and structural alterations that
      were concurrent in one of the cases studied. To our knowledge no cytogenetic data
      are available in myoepitheliomas and cystadenomas. The former reveals a normal
      karyotype and the latter shows only clonal numerical alterations (gain of
      chromosomes 2 and 18).

PMID- 8551732
TI  - Antitumor activity of cis-diamminedichloroplatinum (II) depends on its time x
      concentration product against human gastric cancer cell lines in vitro.
AB  - A pharmacodynamic study of cisplatin (DDP) was conducted using the gastric cancer
      cell lines MKN-45 and MKN-74 in vitro. Ten thousand tumor cells were incubated
      with 0.4-500 micrograms/ml DDP for 1-25 h, followed by recovery culture for a
      further 48 h. At the end of incubation, cell viability was detected by the MTT
      end-point, and the inhibition rate was compared in relation to the incubation
      time, DDP concentration, and the time X concentration product (area under the
      curve in vitro: AUC vitro). In both of the cell lines, the IC50 and IC90 values
      decreased as the exposure time increased, going a linear curve with a slope of
      almost -1, and showing a typical log-log AUC vitro-dependent curve. These results
      indicate that the antitumor activity of DDP is dependent on its AUC vitro,
      suggesting the clinical usefulness of this drug when administered daily in small
      divided doses.

PMID- 8551733
TI  - Adjuvant six cycles of high-dose adriamycin, cyclophosphamide, methotrexate, 5
      fluorouracil (ACMF) vs. 12 cycles of low-dose ACMF with tamoxifen for
      premenopausal, node-positive breast cancer patients: results of a prospective
      randomized study.
AB  - A prospective randomized study was conducted to compare the adjuvant efficacy of
      six cycles of high-dose ACMF (Adriamycin, ADM; cyclophosphamide, CPA;
      methotrexate, MTX; 5-fluorouracil, 5-FU) with that of 12 cycles of low-dose ACMF
      in premenopausal, node-positive breast cancer patients. The six-cycle ACMF group
      (93 patients) received, intravenously (i.v.), 130 mg/m2 CPA, 26 mg/m2 MTX, and
      600 mg/m2 5FU on days 1 and 8, and 26 mg/m2 ADM on day 1 of each cycle. The 12
      cycle ACMF group (97 patients) received i.v. 65 mg/m2 CPA, 13 mg/m2 MTX, and 300
      mg/m2 5-FU on days 1 and 8, and 13 mg/m2 ADM on day 1 of each cycle. These
      treatments were repeated every 4 weeks, and all the patients took tamoxifen (30
      mg/day) for 2 years. The background factors of the two groups were comparable.
      There were non-significant trends toward better disease-free and overall survival
      rates in the high-dose, six-cycle ACMF group. Both treatments were well
      tolerated, but more patients in the low-dose, 12 cycle group refused to continue
      to receive chemotherapy. These data suggest that escalating doses of ACMF over a
      shorter period, even with doses within the conventional range, are superior to
      low-dose prolonged therapy.

PMID- 8551734
TI  - Surgical treatment of non-small cell lung cancer in patients older than seventy
      years.
AB  - Surgical treatment of non-small cell lung cancer has been reported to be
      associated with increased mortality, especially when pneumonectomy has been
      employed. A 9-year review of 81 patients treated surgically, with a policy of
      avoiding pneumonectomy and using internal radiation and wedge excisions rather
      than lobectomy among patients with impaired reserve, resulted in an operative
      mortality of 4.9% compared with an overall mortality of 2.1%. Three of the four
      deaths were among patients older than 80 3/17 (17.6%) years so that mortality of
      patients 70 < age < 80 was not significantly different from overall mortality.
      Two of the four deaths were related to pulmonary emboli but there have been no
      such deaths since routine use of mini-heparin was initiated in 1990. Five-year
      survival was 42% overall, 65% for stage 1, and 24% for stages II-IIIB. We
      conclude that surgical treatment of patients 70 < age < 80 may be accomplished
      with similar mortality and survival as the overall population. Heparin
      prophylaxis may be especially important among patients older than 80 years.

PMID- 8551736
TI  - Intraoperative brachytherapy using Gelfoam radioactive plaque implants for
      resected stage III non-small cell lung cancer with positive margin: a pilot
      study.
AB  - Complete surgical resection of stage III non-small cell lung cancer (NSCLC) is at
      times impossible. Adjuvant radiation therapy is required to sterilize the
      residual tumor. This study is to investigate the safety, reproducibility, and
      effectiveness of intraoperative I-125 or Pd-103 Gelfoam plaque implant technique
      as an adjuvant treatment for resected stage III NSCLC with positive surgical
      margin. Between 1989 and 1993, 12 patients with stage III NSCLC received
      intraoperative lung implant with radioactive I-125 or Pd-103 pellets. All 12
      patients underwent tumor resection, but either gross or microscopic positive
      margin was found during operation. Radioactive I-125 or Pd-103 seeds were
      embedded in the Gelfoam plaque. After surgical resection was completed, the
      radioactive Gelfoam plaque was secured onto the tumor bed either by clips or
      suture. Either preoperative or postoperative external beam radiation of 45-60 Gy
      was given to all of the 12 patients. Four patients received chemotherapy. No
      patient has developed any early or late complications attributable to implant
      procedure or radiation. The local control rate at last follow-up is 82%. The 2
      year overall and cause-specific survival rates are 45% and 56%, respectively. The
      intraoperative Gelfoam I-125 or Pd-103 planar implant technique is a safe,
      reproducible, and effective technique of treatment for stage III NSCLC with a
      positive surgical margin. Encouraging local control and survival are achieved in
      patients treated with this technique. This technique will compliment standard
      adjuvant treatments to further improve local control in resected state III lung
      cancer.

PMID- 8551735
TI  - Ewing's sarcoma of bone: oncologic and functional results.
AB  - This paper describes 29 patients with Ewing's sarcoma of bone treated between
      1975 and 1990 at the University of Nijmegen Hospital, Nijmegen, The Netherlands.
      Osteomyelitis was the primary diagnosis in 24%. Treatment consisted of
      chemotherapy in combination with surgery and/or radiotherapy. Nine patients
      received radiotherapy only; five of them died of disease. Five patients underwent
      an intralesional excision; four of them died of disease. Twelve patients
      underwent a wide excision; there is no evidence of disease in any of them. Three
      patients underwent a radical disarticulation; all died of disease. The disease
      free survival at 1.5 years was 66%. This figure at 5 years was 55%. After wide
      excision and reconstruction in tumors of expendable, femoral or radial bones good
      functional results were obtained in all cases.

PMID- 8551737
TI  - Intrapleural chemotherapy for patients with incompletely resected malignant
      mesothelioma: the UCLA experience.
AB  - From 1986 to 1993, 15 patients with malignant pleural mesothelioma were treated
      by pleurectomy/decortication and intrapleural cisplatin (100 mg/m2) and cytosine
      arabinoside (1,200 mg). All patients were without known extrathoracic disease and
      had a mean age of 63 +/- 7.9 years (range 51-78); 13 were male. Histologic
      subtype of disease were epithelial (47%), sarcomatoid (27%), and mixed-biphasic
      (27%). The major morbidity and mortality rates were 13% and 0%, respectively. The
      mean length of hospital stay was 6.5 +/- 2.1 days. Postoperatively, adjuvant
      chemotherapy and radiation therapy were given to 46% and 73% of the patients
      respectively. Median survival from date of treatment was 11.5 months. Those
      patients with an epithelial histologic subtype experienced significantly improved
      survival compared to those of sarcomatoid subtype (P = 0.024). Whether adjuvant
      chemotherapy or radiation therapy were given had no significant effect on
      survival. These data suggest that although this treatment regimen can be
      administered with very limited morbidity and no mortality, the role of this
      approach in the treatment of malignant pleural mesothelioma appears limited and
      cannot currently be recommended.

PMID- 8551738
TI  - Malignant tumors metastatic to the ovaries.
AB  - One hundred sixty-eight patients treated at Hacettepe Hospital between 1969-1993
      with metastatic ovarian tumors constituted 21.5% of all malignant ovarian
      neoplasms. Primary tumors were endometrial (51), breast (27), colorectal (18),
      and stomach cancer (17), lymphoma (14), sarcoma of the uterus (13), undetermined
      (11), tumors of the appendix (6) and ileum (4), carcinoma of the cervix (4), and
      gestational trophoblastic neoplasia (3). Overall 5-year and median survivals were
      20.0% and 26.8% months, respectively. While worse prognoses were seen in gastric
      cancer and undetermined tumors followed by colorectal cancer, best survival
      figures were observed in endometrial cancer patients. A trend toward a better
      survival was seen with the advancement of the operation from bilateral
      salpingooophorectomy, and/or biopsy to total abdominal hysterectomy, bilateral
      salpingooophorectomy, total omentectomy, pelvic and paraaortic lymphadenectomy
      with debulking. Multivariate analysis identified the primary site, grade,
      laterality of involvement, type of surgery and adjuvant therapy status as
      significant prognostic parameters. Maximal surgical effort followed by adjuvant
      therapy might at least have some short term survival benefit in certain types
      metastatic to the ovaries.

PMID- 8551739
TI  - Synchronous cancers of the esophagus and the ampulla of Vater after distal
      gastrectomy: successful removal of the esophagus, gastric remnant, duodenum, and
      pancreatic head.
AB  - A case of synchronous squamous cell carcinoma of the esophagus and adenocarcinoma
      of the ampulla of Vater after previous gastrectomy is presented. The coexistence
      of these two lesions has never been reported in the English literature. We
      performed a subtotal esophagectomy, total residual gastrectomy, and
      pancreaticoduodenectomy with lymph node dissection in a one-stage procedure. An
      operation of this magnitude could be safely performed with attention to
      meticulous surgical technique and intensive postoperative care. Histological
      examination of the ampulla lesion showed adenocarcinoma with Paneth-cell
      differentiation. This is a rare lesion, and a review of the literature revealed
      only one other case. Neoplastic Paneth cells were also found in lymph node
      metastasis that originated from the ampulla tumor. This case confirms that cells
      with Paneth-cell differentiation can be a significant component in invasive
      carcinoma.

PMID- 8551740
TI  - Thyroid carcinoma metastasized to the sternum: resection of the sternum and
      reconstruction with acrylic resin.
AB  - Recently we resected and reconstructed the sternum in two female patients with
      thyroid carcinoma metastatic to the sternum. Histological diagnosis of the
      metastatic lesion was follicular carcinoma in the first case and papillary
      carcinoma in the second case. Reconstruction of the sternum was accomplished by
      using an acrylic resin plate alone in the first case and an acrylic resin plate
      sandwiched between layers of Marlex mesh (Marlex sandwich procedure) in the
      second case. In the first case the acrylic resin plate was directly fixed to the
      ribs with metallic wires, most of which snapped off later, and a small amount of
      exudate accumulated around the plate for a short period of time. In contrast, the
      postoperative course in the second case was uneventful and the Marlex sandwich
      procedure seemed superior in the chest wall reconstruction following resection of
      the sternum.

PMID- 8551741
TI  - New bedside test to assess feasibility of primary closure after mastectomy for
      locally advanced breast cancer.

PMID- 8551742
TI  - A theoretical analysis of intracellular oxygen diffusion.
AB  - Oxygen diffusion rates within cells may be heterogeneous, with more rapid
      diffusion occurring along intracellular pathways of high oxygen solubility, such
      as mitochondria. Recent experimental data indicate that tissue oxygen
      permeability rises sharply in a temperature range associated with phase
      transitions in lipid membranes suggesting that membranes may function as oxygen
      "pathway". The experimental data have been analyzed using theoretical models of
      diffusion in two-phase media. By assuming muscles to be composed entirely of
      aqueous cytosol and lipids, cytosolic permeability was determined as a function
      of temperature by matching the experimental values of tissue permeability with
      those of model predictions using in vitro values of lipid permeability. Cytosolic
      permeability ranged from 50% of water permeability (low temperature) to 90% of
      water permeability (high temperature) and its temperature dependence was
      distinctly different from that of water. An upper bound for cytosolic
      permeability was calculated using a physiologic value for protein volume
      fraction, and lipid permeability was obtained using this cytosolic permeability.
      A model with a parallel arrangement of lipid and cytosol yielded a value of lipid
      permeability that was 71% higher than the in vitro value. Intracellular
      permeabilities calculated from tissue permeability values were found to be
      inconsistent with experimentally reported values for rat cardiac myocytes.
      Comparison of three different muscles exhibited the same trend of higher
      permeability with higher lipid content. It is concluded that both lipid and
      cytosol permeabilities and, hence, tissue permeabilities are different among
      different muscles and one should exercise caution when data from one muscle is
      used to calculate or extrapolate values in other muscles. It is conceivable that
      muscles with very high mitochondrial content, such as diaphragm and cardiac
      muscles may exhibit an oxygen permeability which is significantly higher than
      commonly accepted values. These results warrant additional measurements of tissue
      oxygen permeability at 37 degrees C, especially for oxidative muscles with high
      lipid content.

PMID- 8551743
TI  - Models of tumor-host interaction as competing populations: implications for tumor
      biology and treatment.
AB  - Population ecology mathematical models examine tumors not as an isolated
      collection of transformed individuals but as part of a dynamic society of
      interacting malignant and normal cells. This approach investigates the mechanisms
      by which a small clone of neoplastic cells is able to replace the much larger and
      previously stable population of normal cells, despite the numerical advantage of
      the latter and the inhibitory effects of the host response. The models define a
      sequence of different stable equilibria with critical mathematical parameters
      which control the outcome of different stages of the neoplasm-host competition-
      parameters which can be correlated with cellular physiologic properties. When
      neoplasm is viewed as a network of interacting tumor and normal populations, a
      unifying hypothesis can be developed that allows the diverse but inconsistent
      properties of transformed cells to be understood according to their specific
      contributions to tumorigenesis within this network. It predicts general sequences
      of genetic changes necessary for tumor survival and invasion and demonstrates
      that apparently disparate properties found in different tumor models can be
      functionally equivalent. The paper proposes novel modes of therapy requiring
      classification and treatment of tumors according to the strategies they employ,
      rather than the traditional criteria of cell type and organ of origin.

PMID- 8551744
TI  - Conditions for soft selection favoring the evolution of hybrid inviability.
AB  - Hybrid inviability per se is not generally considered adaptive; it is believed to
      evolve as a pleiotropic consequence of other genetic changes, either adaptive or
      neutral, between diverging populations. However, given the pre-existence of
      hybrid sterility, there are circumstances under which hybrid inviability may be
      directly selected. In this report, we model the evolution of hybrid inviability
      in the context of within-family density-dependent selection (soft selection).
      This paper shows that under certain conditions, an allele causing hybrid
      inviability can increase when rare, despite also decreasing viability in
      conspecifics. These conditions depend upon the strength of density effects within
      families and upon the frequency of matings with heterospecifics. It is found
      that, under the most favorable conditions (strong soft selection and frequent
      hybridization), the inviability allele can invade when its deleterious effect on
      the hybrid viability exceeds four times its deleterious effects on conspecific
      heterozygotes. The conditions for fixation of the allele are also investigated
      and the circumstances under which this process might operate in natural
      populations are discussed. The conclusion is that the most restrictive condition
      is that for this process to evolve, there must be little opportunity for
      postzygotic reproductive isolation to evolve.

PMID- 8551745
TI  - The structural stability of a three-species food chain model.
AB  - A three-species food-chain model which was previously shown to exhibit chaotic
      dynamics was revisited. By exploring the sensitivity of that result this study
      found that complex behavior depended on the functional form chosen to model the
      interaction between the two highest species in the food chain. Two separate
      scenarios were explored: the gradual addition of refugia modeling the escape from
      predation at low prey densities; and the gradual addition of predator
      interference modeling territorial behavior. The addition of even a small amount
      of refugia provided a stabilizing influence as the chaotic dynamics collapsed to
      stable limit cycles. The results of adding interference to the model were more
      complex. Although the numerical simulations indicated that a low level of
      interference provided a stabilizing influence, the analytical results suggest
      that complex dynamics are possible for a range of parameter values that are
      biologically relevant. The sensitivity of the stability profile to functional
      changes in the model suggests two important ecological motivations for structural
      stability analysis. First, in ecological systems, environmental fluctuations
      cause continuous changes in the functional relationships between and within
      species, resulting in potential changes in the complexity of the dynamics over
      time. Second, slight changes in ecological structure may cause significant
      bifurcations; however, most ecological data are inadequate to distinguish such
      phenomena.

PMID- 8551746
TI  - A mathematical model for biopanning (affinity selection) using peptide libraries
      on filamentous phage.
AB  - A mathematical model is presented for the process of selection of peptides for
      binding to a target. The affinity enrichment process commonly known as biopanning
      relies on subjecting a library of peptides on filamentous phage to a selection
      for binding to the target immobilized on solid support or in solution. The model
      is an implementation of the mass-action law to the diverse population of
      macromolecular assemblies. An analytical solution is presented for the enrichment
      process. Most parameters in the enrichment formula can be easily determined
      experimentally. Two examples corresponding to biopanning with epitope libraries
      and antibody libraries are given. The model allows for an estimation of the
      contribution of equilibrium and dissociative biopanning to the overall
      enrichment. The model can be a tool in the evaluation of the role of different
      biopanning parameters. Its implementation in a spreadsheet makes it possible to
      perform a computer simulation of a biopanning experiment.

PMID- 8551747
TI  - Error propagation in reproduction of diploid organisms. A case study on single
      peaked landscapes.
AB  - Two versions of the diploid selection mutation equation as adapted to sequence
      space are studied. Focussing on diploid generalizations of the well-established
      single peaked landscape, quantitative effects of dominance on error thresholds in
      infinite populations are found, as well as unexpected qualitative features like
      multiple equilibria. Analogues of these phenomena are also recovered in
      stochastic versions for finite populations.

PMID- 8551748
TI  - A mechanism for induction of the SOS response in E. coli: insights into the
      regulation of reversible protein polymerization in vivo.
AB  - During normal DNA replication, RecA, the principal recombinational repair enzyme
      of E. coli, cannot assemble its filament on SSB-bound single-stranded DNA at the
      replication forks. This behavior is paralleled in vitro, where at low Mg2+
      concentrations RecA can not polymerize on SSB-bound single-stranded DNA.
      Inhibition of DNA replication in vivo renders RecA able to polymerize on SSB
      bound single-stranded DNA and to activate the SOS response. Although the
      mechanism of SOS induction is still obscure, abundant in vitro observations
      indicate that RecA filament formation on SSB-bound single-stranded DNA is
      facilitated at elevated concentrations of ATP, Mg2+ and spermidine. It is
      proposed here that inhibition of DNA synthesis in vivo leads to a similar
      accumulation of ATP and its counter-ions, Mg2+ and spermidine, resulting
      ultimately in SOS induction. When DNA synthesis is restored, the concentration of
      ATP, Mg2+ and spermidine returns to normal levels, favoring RecA
      depolymerization. On the basis of the known structure of RecA, a mechanism for
      reversible RecA polymerization is presented. In a RecA polymer, the monomers are
      known to interact with each other primarily through hydrophobic, oppositely
      charged surfaces. In conditions suboptimal for polymerization, these hydrophobic
      surfaces of the monomers are possibly masked by electrostatic interactions with
      other, oppositely charged domains of the monomers. There are known
      recombinational repair proteins whose specific functions are likely to assist in
      RecA polymerization or depolymerization. Features of reversible polymerization of
      eukaryotic proteins tubulin and actin are consistent with the possibility that
      RecA exploits a general principle for the regulation of reversible protein
      polymerization.

PMID- 8551749
TI  - Mathematical modeling of the loss of telomere sequences.
AB  - hortening of telomeres is one of the supposed mechanisms of cellular aging and
      death. An important question related to this so-called "end-replication"
      hypothesis is whether it can explain in quantitative detail the dynamic of cell
      sensescence in vitro and in vivo. A natural way to answer this question is to use
      mathematical modeling. In this paper, the models were successfully fitted to data
      on cultured fibroblasts from two different sources assuming that after reaching
      the Hayflick checkpoint on a single chromosome cells cease to proliferate. The
      main conclusion is that the end-replication hypothesis provides an explanation
      for the cell aging process which is quantitatively consistent with the data. As a
      secondary outcome, estimates were obtained of the rate of shortening of telomeres
      and several interesting mathematical results for branching processes with
      infinite type spaces arise.

PMID- 8551750
TI  - Uniqueness and multiplicity of steady states in monocyclic enzyme cascades: a
      graph-theoretic analysis.
AB  - Monocyclic enzyme cascades are important regulators of biochemical reactions in
      living cells. The reaction network may have either one steady state or many,
      depending on its structure. The occurrence of multiple steady states has
      important biological implications. A simple graph-theoretic method has been
      applied to five reaction mechanisms--which together cover many common monocyclic
      cascades--to determine which mechanisms generate just one steady state and which
      ones allow more than one state. It is shown that an unstable steady state in a
      multiplicity region can be usefully exploited and that in some cases transitions
      may occur between uniqueness and multiplicity regions. The possible effects of
      such transitions are discussed.

PMID- 8551751
TI  - Can tetraplex recombination models explain observations in induced mitotic gene
      conversion?
AB  - Induced mitotic gene conversion studies on the CYC1 gene of yeast have shown that
      the actual base pair changes, the types of changes (base substitution, deletion
      or addition) and the distances between mutations all affect gene conversion
      yields. In crosses between mutations less than four bases apart, gene conversion
      rates are as low as back mutation rates. The same mutants crossed to alleles more
      than five bases away may recombine 50-fold more. In crosses between mutations
      five or more base pairs apart, recombination rates varying by up to ten-fold are
      observed when comparing mutations at the same codon sites. The actual mutations
      in crosses affect recombination rates at these distances. The data rules out
      models in which mutants are repaired independently. Models with large gaps at the
      initiation site are ruled out if the mutants are within the gap. Recombination
      models are favoured in which both mutations can interact at a distance to affect
      the probability of recombination; such interactions may reflect the geometry of
      the recombinational junctions. The specific interactions proposed are that the
      actual mutations, and residual mismatches arising on excision resynthesis, affect
      both the further migration of the recombinational junction, and the probability
      that excision-repair will detect and correct residual mismatches. Junction models
      in which interactions are expected include those composed of base tetraplexes.
      The data is interpreted in terms of these models. Meiotic recombination data is
      consistent with these models.

PMID- 8551752
TI  - Was it an ancient gene codifying for a hairpin RNA that, by means of direct
      duplication, gave rise to the primitive tRNA molecule?
AB  - Some sequences of transfer RNAs (tRNAs) which are believed to possess many of the
      characteristics of the ancestral sequence of this molecule are constructed.
      Analysis of these ancestral sequences seems to indicate that: (i) self-alignment
      of these sequences makes it possible for the 3'-half of the reconstructed
      molecule to display a significant similarity to the 5'-half, thus indicating that
      the two halves of tRNA might be paralogous, and (ii) the 5'-half of the ancestral
      tRNA can reconstruct an almost perfect hairpin structure. These observations give
      weight to the hypothesis suggesting that the primitive tRNA molecule may have
      originated through direct duplication of an ancient gene codifying for a hairpin
      structure.

PMID- 8551753
TI  - Surface-bound heparin fails to reduce thrombin formation during clinical
      cardiopulmonary bypass.
AB  - The hypothesis that heparin-coated perfusion circuits reduce thrombin formation
      and activity; fibrinolysis; and platelet, complement, and neutrophil activation
      was tested in 20 consecutive, randomized adults who had cardiopulmonary bypass.
      Twenty identical perfusion systems were used; in 10, all blood-contacting
      surfaces were coated with partially degraded heparin (Carmeda process; Medtronic
      Cardiopulmonary, Anaheim, Calif.). All patients received a 300 U/kg dose of
      heparin. Activated clotting times were maintained longer than 400 seconds.
      Cardiopulmonary bypass lasted 36 to 244 minutes. Blood samples for platelet
      count, platelet response to adenosine diphosphate, plasma beta-thromboglobulin,
      inactivated complement 3b, neutrophil elastase, fibrinopeptide A, prothrombin
      fragment F1.2, thrombin-antithrombin complex, tissue plasminogen activator,
      plasminogen activator inhibitor-1, plasmin alpha 2-antiplasmin complex, and D
      dimer were obtained at these times: after heparin was given, 5 and 30 minutes
      after cardiopulmonary bypass was started, within 5 minutes after bypass was
      stopped, and 15 minutes after protamine was given. After cardiopulmonary bypass,
      tubing segments were analyzed for surface-adsorbed anti-thrombin, fibrinogen,
      factor XII, and von Willebrand factor by radioimmunoassay. Heparin-coated
      circuits significantly (p < 0.001) reduced platelet adhesion and maintained
      platelet sensitivity to adenosine diphosphate (p = 0.015), but did not reduce
      release of beta-thromboglobulin. There were no significant differences between
      groups at any time for fibrinopeptide A, prothrombin fragment F1.2, or thrombin
      antithrombin complex or in the markers for fibrinolysis: D-dimer, tissue
      plasminogen activator, plasminogen activator inhibitor-1, and alpha 2-antiplasmin
      complex. In both groups, concentrations of prothrombin fragment F1.2 and thrombin
      antithrombin complex increased progressively and significantly during
      cardiopulmonary bypass and after protamine was given. Concentrations of D-dimer,
      alpha 2-antiplasmin complex, and plasminogen activator inhibitor-1 also increased
      significantly during bypass in both groups. Fibrinopeptide A levels did not
      increase during bypass but in both groups increased significantly after protamine
      was given. No significant differences were observed between groups for levels of
      inactivated complement 3b or neutrophil elastase. Radioimmunoassay showed a
      significant increase in surface-adsorbed antithrombin on coated circuits but no
      significant differences between groups for other proteins. We conclude that
      heparin-coated circuits used with standard doses of systemic heparin reduce
      platelet adhesion and improve platelet function but do not produce a meaningful
      anticoagulant effect during clinical cardiopulmonary bypass. The data do not
      support the practice of reducing systemic heparin doses during cardiac operations
      with heparin-coated extracorporeal perfusion circuitry.

PMID- 8551754
TI  - Objective assessment of gastroesophageal reflux after short esophagomyotomy for
      achalasia with the use of manometry and pH monitoring.
AB  - The role of an antireflux procedure as an adjunct to esophagomyotomy for
      achalasia remains a subject of controversy. Little objective documentation exists
      of this operation's effect on sphincteric competence and the degree of
      postoperative gastroesophageal reflux. This report of esophageal manometry and 24
      hour pH monitoring on 14 patients with esophageal achalasia whom we had
      previously treated by a short esophagomyotomy without an antireflux procedure
      provides such documentation. Esophagomyotomy reduced lower esophageal sphincter
      pressure by 12% to 71% (mean 41%) from a preoperative mean of 26.7 mm Hg to a
      postoperative mean of 14.6 mm Hg. The number of postoperative episodes of acid
      reflux per patient in 24 hours was fewer than 29 (normal < 49) in 13 patients,
      with a median of 12 episodes for the entire group. Esophageal acid exposure,
      measured as percentage of total time with pH less than 4.0 (normal < 4.5%), was
      below 4.5% in 10 patients, six of whom had values less than 1%. Among the four
      patients with values greater than 4.5%, only one had a temporal correlation of
      symptoms with an episode of acid reflux. Multivariate analysis showed that
      esophageal acid exposure time correlated only with the level of residual lower
      esophageal sphincter pressure during the relaxation phase of deglutition. A
      pressure less than 8 mm Hg was predictive of normal acid contact time (p <
      0.001). Mean lower esophageal sphincter pressure, percent reduction in lower
      esophageal sphincter amplitude, postoperative vector volume, and length of the
      lower esophageal sphincter did not significantly correlate with amount of
      esophageal acid exposure. We conclude that a short esophagomyotomy without an
      antireflux procedure results in a competent lower esophageal sphincter in most
      patients. Increased esophageal acid exposure, when it occurs, is due to slow
      clearance of esophageal acid from relatively few reflux episodes and is more
      likely to occur when there is a high residual pressure during deglutition after
      myotomy. These findings suggest that the addition of an antireflux procedure to a
      short esophagomyotomy would not be expected to improve clinical results.

PMID- 8551755
TI  - Delayed primary repair of intrathoracic esophageal perforation: is it safe?
AB  - The management of intrathoracic esophageal perforation with delayed diagnosis is
      a subject of controversy. Because of the obvious advantages of primary repair as
      a simple single-stage operation, this technique was preferentially used to treat
      18 of 22 consecutive patients with esophageal perforation. These patients were
      stratified into three groups according to the time interval between perforation
      and repair: group A, less than 6 hours, five patients (28%); group B, 6 to 24
      hours, six patients (33%); and group C, more than 24 hours, seven patients (39%).
      Group A patients were older (p < 0.05) and group B had fewer iatrogenic
      perforations (B, 17%; A, 80%; C, 57%, p < 0.1). Additional tissue was used to
      buttress the repair site in all three groups (A, 3/5 patients, 60%; B, 4/6
      patients, 67%; C, 6/7 patients, 86%; p = not significant). In seven patients
      (39%), a fundic wrap was used to reinforce the site of primary repair. The
      outcomes of the three groups were analyzed. Group A had the lowest proportion of
      postoperative leaks (A, 0/4 patients, 0%; B, 4/6 patients, 67%; C, 5/6 patients,
      83%; p < 0.05) and postoperative morbidity (A, 2/5 patients, 40%; B, 6/6
      patients, 100%; C, 6/7 patients, 86%; p < 0.1). However the increased incidence
      of leak and morbidity did not lead to an increase in mortality. One death
      occurred in each group, with an overall mortality of 17% (A, 1/5 patients, 20%;
      B, 1/6 patients, 17%; C, 1/7 patients, 14%; p = not significant). We conclude
      that in the era of advanced intensive care capabilities, primary repair of
      intrathoracic esophageal perforation can be safely accomplished in most patients
      regardless of the time interval between perforation and operation. Leakage at the
      suture site is common unless primary repair is carried out without delay.
      Postoperative leakage, however, is usually inconsequential and does not
      necessarily result in an adverse outcome.

PMID- 8551756
TI  - Assessment of preoperative accelerated radiotherapy and chemotherapy in stage
      IIIA (N2) non-small-cell lung cancer.
AB  - Forty patients with N2 non-small-cell lung cancer (stage IIIA), as determined by
      mediastinoscopy, were entered into a preoperative neoadjuvant study of
      chemotherapy (platinum, 5-fluorouracil, vinblastine) and accelerated radiotherapy
      (150 cGy twice per day for 7 days) for two cycles. Surgical resection was then
      performed and followed up with an additional cycle of chemotherapy and
      radiotherapy. All patients completed preoperative therapy. A major clinical
      response was seen in 87% of patients. Thirty-five patients underwent resection
      (one preoperative death, one refused operation, one had deterioration of
      pulmonary function, and two had pleural metastases). Operative mortality rate was
      5.7% (2/35). Sixty percent of patients had no complications. Major complications
      included pulmonary emboli (three), pneumonia (two), and myocardial infarction
      (one). Down-staging was seen in 46% of patients, with two patients (5.7%) having
      no evidence of tumor in the specimen, five patients having sterilization of all
      lymph nodes, and nine patients having sterilization of mediastinal nodes but
      positive N1 nodes. Median survival of 40 patients was 28 months, with a projected
      5-year survival of 43%. Patients with downstaged disease had statistically
      significant improved survival compared with patients whose disease was not
      downstaged.

PMID- 8551757
TI  - Miniature axial flow pump for ventricular assistance in children and small
      adults.
AB  - We investigated the efficacy of the Jarvik 2000 intraventricular assist device
      (Jarvik Research, Inc., New York, N.Y.) in an ovine model. The device is an axial
      flow pump measuring 1.8 cm in diameter by 5 cm long, has a displacement volume of
      12 ml, and can deliver flow from 2 to 7 L/min. Seven devices were implanted
      through a left thoracotomy into the left ventricle with an outflow graft to the
      descending aorta. Animals were treated with warfarin sodium and aspirin to
      maintain prothrombin times approximately 1.5 times control. Animals were followed
      up for 3 to 123 days. Two animals died of operative complications at days 3 and
      5. One device failed at 58 days because of thrombus formation at the inflow side
      of the impeller. The remaining four animals were killed at days 19, 42, 42, and
      123, respectively, because of broken electric power cables. Hematocrit values
      rose significantly higher than preoperative levels (22.8% +/- 3.8% to 30.5% +/-
      3.4%); premortem elevations of values higher than baseline values of plasma free
      hemoglobin (10.4 +/- 7.8 mg/dl to 17.1 +/- 7.4 mg/dl) and lactate dehydrogenase
      (391.5 +/- 113.7 units/L to 771.2 +/- 370.8 units/L) were statistically
      insignificant. Serum creatinine and bilirubin levels were normal. No end-organ
      dysfunction arising from long-term support was evident clinically or at
      postmortem examination, nor was there any evidence of embolism or damage to
      intracardiac structures. We found the Jarvik 2000 intraventricular assist device
      to be easily implantable, safe, nonhemolytic, and able to provide physiologic
      flow with power requirements under 10 watts.

PMID- 8551758
TI  - Thymic neuroendocrine carcinoma (carcinoid): a clinicopathologic study of
      fourteen cases.
AB  - The medical records and histologic documents of 14 patients treated at our
      institution for a thymic carcinoid tumor were reviewed. There were 3 women and 11
      men with an age range from 35 to 71 years. One patient had a multiple endocrine
      neoplasia syndrome; another had a neurofibromatosis. Twelve tumors were revealed
      by local symptoms and two were asymptomatic. One patient had Cushing's syndrome
      that appeared secondarily and was related to metastases. Tumors ranged from 6 to
      20 cm and had the characteristic histologic appearance of atypical carcinoid
      tumor. Immunohistochemical evaluations were done. Tumors were positive for
      cytokeratin (92%), neuroendocrine markers (100%), and p53 oncoprotein (29%). S
      100 protein antibody revealed numerous sustentacular cells in one case. Overall
      survival was 46% and 31% at 3 and 5 years, respectively. However, all patients
      died of the disease within 109 months as a result of local progression (n = 5),
      local relapse (n = 3), distant metastases (n = 8), or a combination of these
      reasons. Median survival was 71, 30, and 5 months for patients who had total
      resection (n = 4), partial resection (n = 5), or simple biopsy (n = 4),
      respectively (p = 0.023). In conclusion, thymic carcinoid tumors can be
      considered thymic neuroendocrine carcinomas because of their malignant behavior
      and histologic appearance of atypical carcinoid tumors. Complete surgical
      resection offers the best hope for long-term survival.

PMID- 8551759
TI  - Stapler design and strictures at the esophagogastric anastomosis.
AB  - An apparent reduction in the rate of benign anastomotic stricture after stapled
      esophagogastrectomy prompted us to review the results obtained with different
      stapling devices since 1988. We present a retrospective review of 125 consecutive
      patients undergoing esophageal resection for malignancy with stapled
      intrathoracic anastomoses. Benign anastomotic stricture was deemed present when a
      patient required endoscopic dilatation to treat postoperative dysphagia. We found
      no difference in risk factors not related to stapler size (tumor histologic
      characteristics, adjuvant therapy) between patients with stricture and patients
      without stricture. Event-free survival was compared for different stapler
      diameters as well as for different stapler designs. We found that staplers of
      smaller diameter were associated with significantly more strictures (p < 0.005).
      In a comparison of different designs of 25 mm stapler, the newer CDH device
      (Ethicon Ltd., Edinburgh, United Kingdom) was associated with a similar stricture
      rate to that associated with other designs (ILP [Ethicon] and EEA [Autosuture
      Company Division, United States Surgical Corp., Norwalk, Conn.]). For a given
      stapler diameter, it appears that different stapler designs have no effect on
      stricture rate.

PMID- 8551760
TI  - pH-stat cooling improves cerebral metabolic recovery after circulatory arrest in
      a piglet model of aortopulmonary collaterals.
AB  - Cardiopulmonary bypass with deep hypothermic circulatory arrest increases the
      risk of neurologic injury in patients with aortopulmonary collaterals.
      Experimental studies have demonstrated that such collaterals decrease the rate of
      cerebral cooling before arrest and cerebral metabolic recovery after circulatory
      arrest. Use of pH-stat blood gas management has been shown to increase cerebral
      blood flow during cooling. The current study was designed to test whether cooling
      with pH-stat blood gas management can decrease the cerebral metabolic impact of
      aortopulmonary collaterals. Twenty 4- to 6-week-old piglets underwent placement
      of a shunt between the left subclavian artery and main pulmonary artery. In
      control animals (n = 10) the shunts were immediately ligated, whereas in the
      shunt animals (n = 10) the shunts were left patent. All animals were supported
      with cardiopulmonary bypass, cooled to 18 degrees C by means of either alpha-stat
      (five control and five shunt animals) or pH-stat (five control and five shunt
      animals) blood gas management, subjected to circulatory arrest for 90 minutes,
      and rewarmed to 37 degrees C. The cerebral metabolic rate of oxygen consumption
      (a marker for neurologic function) was significantly lower after circulatory
      arrest in the shunt animals cooled with alpha-stat blood gas management than in
      the control animals subjected to alpha-stat management (1.2 +/- 0.2 vs 2.3 +/-
      0.2 ml oxygen per 100 gm/min, p < 0.05). By contrast, there was no difference
      between the pH-stat shunt animals and either control group (2.1 +/- 0.2 vs 2.3 +/
      0.2 [alpha-stat] and 2.0 +/- 0.3 [pH-stat] ml oxygen per 100 gm/min, p = not
      significant). pH-Stat cooling protected the brain from shunt-related injury. When
      circulatory arrest is used in the presence of aortopulmonary collaterals, the use
      of pH-stat blood gas management during cooling results in better cerebral
      protection than alpha-stat blood gas management.

PMID- 8551761
TI  - Aortoventriculoplasty with the pulmonary autograft: the "Ross-Konno" procedure.
AB  - BACKGROUND: For patients with complex left ventricular outflow tract obstruction,
      including hypoplastic aortic anulus with or without severe diffuse subaortic
      stenosis, various aortoventriculoplasty procedures (e.g., Konno procedure and its
      modifications; extended aortic allograft root replacement) are important
      management options. In younger patients, however, reoperation for valve
      replacement is inevitably required, and anticoagulation issues pose additional
      problems. The pulmonary autograft provides a promising option for aortic valve
      replacement as part of the aortoventriculoplasty procedure in children. Long-term
      follow up shows that the pulmonary autograft functions well as the systemic
      arterial (neoaortic) valve and that valve growth occurs. METHODS: Between July
      1993 and May 1995, 11 patients 4 days to 17 years old (median 12 months)
      underwent aortoventriculoplasty with pulmonary autograft (Ross-Konno procedure).
      The diagnoses were aortic stenosis with or without subaortic stenosis (n = 8),
      Shone complex (n = 2), and interrupted aortic arch with subaortic stenosis (n =
      1). On average, 1.9 previous interventions had been performed per patient,
      including a previous Konno procedure in one patient. The aortic root was replaced
      with a pulmonary autograft valve. The left ventricular outflow tract was enlarged
      with a Dacron polyester fabric patch in two patients, with an allograft aortic
      patch in two patients and a right ventricular infundibular free wall muscular
      extension harvested in continuity with the autograft in seven patients. RESULTS:
      Intraoperative transesophageal echocardiographic assessment revealed mild aortic
      insufficiency in one patient. One patient had a residual left ventricular outflow
      tract gradient of 15 mm Hg. Significant complications were cardiac tamponade from
      bleeding (n = 1) and complete heart block necessitating a permanent pacemaker (n
      = 1). Follow-up ranged from 2 weeks to 16 months. To date, there have been no
      late deaths or reoperations. Follow-up echocardiography revealed mild autograft
      insufficiency in one patient and a 16 mm Hg residual left ventricular outflow
      tract gradient in one patient. CONCLUSIONS: Initial experience suggests that
      aortoventriculoplasty with the pulmonary autograft is an excellent alternative
      for young patients with complex left ventricular outflow tract obstruction.
      Because the pulmonary autograft has been shown to grow after implantation,
      reoperation on the left ventricular outflow tract is likely to be avoided.

PMID- 8551762
TI  - Decision making for the surgical management of aortic coarctation associated with
      ventricular septal defect.
AB  - Coarctation of the aorta and associated ventricular septal defect may be repaired
      simultaneously or by initial coarctation repair with or without banding of the
      pulmonary artery. The question is whether specific preoperative criteria can
      enable the surgeon to choose the optimal surgical management. Between 1980 and
      1993, 80 infants younger than 3 months with coarctation and ventricular septal
      defect were treated surgically. In 64 infants (multistage group), simple
      coarctation repair was performed through a posterolateral approach, with
      concomitant banding of the pulmonary artery in 10 infants. Twenty ventricular
      septal defects were closed as a secondary procedure and four were closed as a
      tertiary procedure. Sixteen infants (single-stage group) underwent one-stage
      repair through an anterior midline approach. The total in-hospital mortality rate
      was 7.5%. Freedom from recoarctation after 5 years was 91.3% in the multistage
      group versus 60.0% in the single-stage group (p = 0.018). Freedom from secondary
      ventricular septal defect treatment in the multistage group after 5 years was
      40.7%, versus 100% in the single-stage group (p = 0.016). Thirty-seven
      ventricular septal defects (47.8%) closed spontaneously. In particular, the
      preoperative left-to-right shunt and extension of the perimembranous VSD into the
      inlet or outlet were risk factors for the need for eventual surgical ventricular
      septal defect closure after initial coarctation repair. On the basis of these two
      risk factors, the probability of the need for eventual surgical treatment of
      ventricular septal defect after initial coarctation repair can be calculated.
      This policy offers a well-considered choice between single-stage and multistage
      repair, weighing the risk of secondary ventricular septal defect treatment versus
      the risk of recoarctation. Finally, the number of surgical procedures per infant
      will be as low as possible.

PMID- 8551763
TI  - Augmentation of pulmonary blood flow with an axillary arteriovenous fistula after
      a cavopulmonary shunt.
AB  - Of 320 children with cyanotic congenital heart malformations who had previously
      undergone cavopulmonary shunt operations, 11 had increasing cyanosis and exercise
      intolerance and were considered unsuitable for definitive repair, a Fontan
      procedure, or other palliation. Eight had a previous Glenn shunt and three had a
      previous bidirectional cavopulmonary connection. To augment pulmonary blood flow,
      10 patients underwent creation of an ipsilateral axillary arteriovenous fistula.
      Mean oxygen saturations were 80% +/- 2% before operation, 85% +/- 2% immediately
      after operation, and 84% +/- 3% at a mean follow-up interval of 7.4 years (range
      0.1 to 15.5 years). Mean hemoglobin values were 202 +/- 10 gm/L before operation,
      177 +/- 10 gm/L after operation, and 191 +/- 14 gm/L at latest review. The only
      complication was mild swelling of the arm distal to the fistula in one patient.
      All patients reported improvement in exercise tolerance. Eight patients have
      continued evidence of fistula patency. Development of ipsilateral pulmonary
      arteriovenous fistulas has not been observed in any patient. Creation of an
      axillary arteriovenous fistula to augment pulmonary blood flow after a
      cavopulmonary shunt provides useful palliation for complex cyanotic heart disease
      when other options are limited. Such additional sources of pulmonary blood flow
      may influence the development of pulmonary arteriovenous fistulas.

PMID- 8551764
TI  - Expanding indications for pediatric coronary artery bypass.
AB  - Pediatric coronary artery bypass has been done mostly for ischemic complications
      of Kawasaki disease. We reviewed our clinical experience between 1987 and 1994
      with internal thoracic artery-coronary artery bypass in one infant and five
      children for varying indications. Indications for coronary bypass included
      Kawasaki disease (2), congenital left main coronary ostial stenosis, iatrogenic
      coronary cameral fistula, anomalous origin of the left coronary artery from the
      pulmonary artery, and single coronary artery traversing between the great
      arteries in a patient after cardiac transplantation. An additional cohort of 34
      control patients of various ages and weights (1 day to 16.1 years, 2.6 kg to 62
      kg) had angiographic measurements of the right coronary, left coronary, and left
      internal thoracic arteries with respect to the feasibility of performing coronary
      artery bypass. All six patients survived internal thoracic artery-left anterior
      descending coronary artery bypass without evidence of perioperative myocardial
      infarction. Postoperative angiographic studies in five and color Doppler
      echocardiography in one showed graft patency. Retrospective angiographic
      measurements in the 34 control patients showed that internal thoracic and
      coronary arteries are proportionately quite large in neonates and infants
      compared with those in older children and adolescents. Internal thoracic artery
      coronary artery bypass should be considered for the expanding indications
      presented herein and when emergency intraoperative life-threatening situations
      present themselves. Long-term patency and reoperation rates have yet to be
      determined.

PMID- 8551765
TI  - The effect of basic fibroblast growth factor on the blood flow and morphologic
      features of a latissimus dorsi cardiomyoplasty.
AB  - Previous studies designed to determine whether latissimus cardiomyoplasty could
      be used to revascularize ischemic myocardium showed that after operation the
      latissimus was ischemic and had severely deteriorated. This study was undertaken
      to determine whether basic fibroblast growth factor, a potent angiogenic peptide,
      would improve the vascularity of the latissimus and enhance collateral formation
      between the muscle of the cardiomyoplasty and ischemic myocardium. In goats,
      myocardial ischemia was induced with an ameroid constrictor and cardiomyoplasty
      performed. The latissimus was continuously stimulated electrically at 2 Hz for 6
      weeks and given four weekly bolus injections of human recombinant basic
      fibroblast growth factor (80 micrograms infused into the left subclavian artery).
      In eight animals, rates of regional blood flow were measured and both the heart
      and latissimus were evaluated histochemically. The latissimus blood flow rate was
      0.114 +/- 0.029 ml/gm per minute, which was three times greater than that of
      historical controls (chronically stimulated latissimus cardiomyoplasty without
      basic fibroblast growth factor treatment; 0.042 +/- 0.007 ml/gm per minute, p <
      0.05). Associated with the improved blood flow, there was significantly less
      evidence of skeletal muscle fiber dropout and muscle fibrosis in the animals
      treated with basic fibroblast growth factor. Latissimus-derived collateral flow
      to ischemic myocardium developed in five of the eight goats and averaged 0.288 +/
      0.075 ml/gm per minute. This flow was 42.8% +/- 15.7% (n = 5) of the flow
      required by normal myocardium (which was 0.728 +/- 0.095 ml/gm per minute). This
      value for latissimus-derived collateral blood flow was almost twice that of the
      historical controls (24.0% +/- 3.9%), but the increase did not achieve
      statistical significance (p = 0.08). These results hold the promise that basic
      fibroblast growth factor treatment might enhance the formation of extramyocardial
      collaterals to the heart and improve skeletal muscle function.

PMID- 8551766
TI  - Pulmonary vasomotor dysfunction is produced with chronically high pulmonary blood
      flow.
AB  - This study examined the hypothesis that chronic high pulmonary blood flow
      produces dysfunction of the mechanisms of pulmonary vasorelaxation. A 3:1 left-to
      right shunt was created in dogs by bilateral femoral artery-femoral vein shunts
      with use of 6 mm polytetrafluoroethylene grafts. Isolated pulmonary artery rings
      were studied at the following times: 3 days (n = 2), 2 weeks (n = 4), and 5
      months (n = 6). Control animals had no shunt. The following mechanisms of
      pulmonary vasorelaxation were studied in isolated pulmonary artery rings (4 rings
      from each dog): (1) endothelium-dependent cyclic guanosine monophosphate-mediated
      relaxation (response to acetylcholine), (2) endothelium-independent cyclic
      guanosine monophosphate-mediated relaxation (response to sodium nitroprusside),
      and (3) beta-adrenergic cyclic adenosine monophosphate-mediated relaxation
      (response to isoproterenol). Statistical analysis was done by analysis of
      variance. This model of high pulmonary flow did not produce an increase in
      pulmonary arterial pressure or transpulmonary gradient. However, chronic high
      pulmonary flow produced progressive dysfunction of all three of these mechanisms
      of pulmonary vasorelaxation. By 5 months of high pulmonary flow, acetylcholine
      produced only 36% +/- 6% relaxation versus 95% +/- 5% in control animals (p <
      0.05). Likewise, sodium nitroprusside produced only 69% +/- 6% relaxation versus
      100% in control animals (p < 0.05). Finally, isoproterenol produced only 55% +/-
      5% relaxation versus 94% +/- 6% in control animals (p < 0.05). We conclude that
      dysfunction of the mechanisms of pulmonary vasorelaxation may contribute to
      exaggerated perioperative pulmonary vasoconstriction in the setting of chronic
      high pulmonary blood flow.

PMID- 8551767
TI  - Surgical treatment of prosthetic valve endocarditis.
AB  - From 1975 through 1992, we reoperated on 146 patients for the treatment of
      prosthetic valve endocarditis. Prosthetic valve endocarditis was considered to be
      early (< 1 year after operation) in 46 cases and active in 103 cases. The extent
      of the infection was prosthesis only in 66 patients, anulus in 46, and cardiac
      invasion in 34. Surgical techniques evolved in the direction of increasingly
      radical debridement of infected tissue and reconstruction with biologic
      materials. All patients were treated with prolonged postoperative antibiotic
      therapy. There were 19 (13%) in-hospital deaths. Univariate analyses demonstrated
      trends toward increasing risk for patients with active endocarditis and extension
      of infection beyond the prosthesis; however, the only variables with a
      significant (p < 0.05) association with increased in-hospital mortality confirmed
      with multivariate testing were impaired left ventricular function, preoperative
      heart block, coronary artery disease, and culture of organisms from the surgical
      specimen. During the study period, mortality decreased from 20% (1975 to 1984) to
      10% (1984 to 1992). For hospital survivors the mean length of stay was 25 days.
      Follow-up (mean interval 62 months) documented a late survival of 82% at 5
      postoperative years and 60% at 10 years. Older age was the only factor associated
      (p = 0.006) with late death. Nineteen patients needed at least one further
      operation; reoperation-free survival was 75% at 5 and 50% at 10 postoperative
      years. Fever in the immediate preoperative period was the only factor associated
      with decreased late reoperation-free survival (p = 0.032). Prosthetic valve
      endocarditis remains a serious complication of valve replacement, but the in
      hospital mortality of reoperations for prosthetic valve endocarditis has
      declined. With extensive debridement of infected tissue and postoperative
      antibiotic therapy, the extent and activity of prosthetic valve endocarditis does
      not appear to have a major impact on late outcome, and the majority of patients
      with this complication survive for 10 years after the operation.

PMID- 8551768
TI  - Repair of chordae tendineae for rheumatic mitral valve disease. A twenty-year
      experience.
AB  - Sixty-two patients with rheumatic mitral valve disease (mean age 42.2 +/- 10.2
      years) underwent repair of chordae tendineae between June 1974 and May 1994.
      Chordal shortening was done in 38 patients, fenestration in 17, resection of
      secondary chordae in 3, replacement in 2, and transposition in 2. In 41 patients,
      mitral commissurotomy was also done. Ring annuloplasty was done in all patients.
      The mean follow-up was 10.2 years (range 2 months to 20 years). The completeness
      of follow-up during the closing interval (January to July 1994) was 100%.
      Hospital mortality occurred in four patients (6.5%) and nine patients died during
      the late follow-up. The actuarial survival curve at 20 years was 65.8% +/- 10%.
      Six patients with mitral valve dysfunction (restenosis 4, insufficiency 2) and
      one with aortic valve dysfunction (structural deterioration of bioprosthesis)
      underwent reoperation. The actuarial curve of freedom from reoperation at 20
      years for mitral valve dysfunction was 73.1% +/- 10.5%. In the 49 surviving
      patients, a Doppler echographic study during the closing interval showed a mean
      mitral valve area of 1.9 +/- 0.3 cm2. In the 43 patients with a repaired native
      valve, absent or trivial mitral regurgitation was documented in 35 and mild or
      moderate regurgitation in 8. In conclusion, repair of chordae tendineae in
      rheumatic mitral valve disease when feasible is a stable and safe procedure with
      a low prevalence of reoperation. However, the type of reconstructive operation
      and experience of the surgical team are major considerations in successful repair
      of the mitral valve.

PMID- 8551769
TI  - Effects of storage temperature and fetal calf serum on the endothelium of porcine
      aortic valves.
AB  - Endothelial integrity and function may be an important determinant for long-term
      success of allograft heart valves. To determine the optimal storage temperatures
      for preservation of long-term endothelial function in porcine aortic valves,
      different storage temperatures and times were investigated. Fresh valves were
      either (1) stored at 4 degrees C, with or without 10% fetal calf serum
      supplement, for 1, 2, 4, 7, 14, 21, or 28 days; (2) cryopreserved for 2, 4, or 8
      weeks at -80 degrees C or -170 degrees C; (3) cryopreserved in long-term storage
      (as long as 1 year), with or without fetal calf serum, at -170 degrees C.
      Viability of endothelial cells was assessed through measurement of the production
      of prostacyclin in basal and bradykinin-stimulated conditions, during in vitro
      incubation of the valve cusps at 37 degrees C. Endothelial morphologic variations
      in valves stored at 4 degrees C were evaluated by scanning electron microscopy.
      With storage at 4 degrees C, after 4 days the valves already produced
      significantly less (p < 0.05) prostacyclin than fresh preparations in both basal
      (0.21 +/- 0.04 versus 3.56 +/- 0.03 ng.ml-1.cm-2) and stimulated conditions (4.17
      +/- 0.36 vs 24.23 +/- 1.83). Morphologic changes could not yet be distinguished
      with scanning electron microscopy at that time. When the storage period was
      extended, the levels of prostacyclin further diminished; after 14 days,
      prostacyclin release could no longer be detected. In cryopreserved valves,
      prostacyclin production was similar for as long as 2 weeks of storage either at 
      80 degrees C or at -170 degrees C in basal (2.69 +/- 0.63 vs 2.93 +/- 0.51) and
      stimulated (16.43 +/- 3.19 vs 16.50 +/- 2.57, = 6) conditions. After 8 weeks, no
      prostacyclin release could be detected in valves stored at -80 degrees C. After 6
      months storage at -170 degrees C, the prostacyclin production was significantly
      (p < 0.05) reduced compared with fresh valves; it then remained constant for as
      long as 1 year. The valves stored with fetal calf serum produced significantly (p
      < 0.05) less prostacyclin than did those without fetal calf serum. For longer
      cryopreserved banking, we recommend storing heart valves at -170 degrees C
      instead of at -80 degrees C to maintain viability of endothelial cells. Fetal
      calf serum would harm endothelial viability during long-term cryopreservation.

PMID- 8551770
TI  - Atrial compartment surgery for chronic atrial fibrillation associated with
      congenital heart defects.
AB  - In three adult patients, two with atrial septal defect and one with Ebstein's
      anomaly, chronic atrial fibrillation was documented for 13, 21, and 3 years,
      respectively. Atrial compartment surgery was performed for ablation of the atrial
      fibrillation concomitant with repair of the cardiac defects. The operation was
      performed with traditional cardiopulmonary bypass and crystalloid cardioplegia
      myocardial protection. A U-shaped incision was made in the right atrium: a
      longitudinal incision 1 cm lateral and parallel to the sulcus terminalis,
      extending along the borders of the atrial septum to 3 cm (upper margin) and 1 cm
      (lower margin) distant to the tricuspid anulus. Cryolesions of the atrial isthmus
      between the upper incision margin and the tricuspid valve anulus were created at 
      60 degrees C for 180 seconds at a time. After the operation, all three patients
      had restored and maintained normal sinus rhythm during follow-up periods of 32,
      16, and 3 months. Doppler echocardiography detected the recovery of atrial
      contractility in all three patients. Atrial compartment surgery is a simple and
      effective method for elimination of chronic atrial fibrillation associated with
      congenital heart defects.

PMID- 8551771
TI  - Aging reduces postischemic recovery of coronary endothelial function.
AB  - The aging process is known to be associated with profound changes in the heart.
      To determine whether resistance of coronary endothelial and vascular smooth
      muscle function to ischemia may be related to age, four groups of rats (n = 6 in
      each group) of different ages (1, 5, 15, and 26 months) were subjected to
      cardioplegic arrest for 4 hours at 4 degrees C. The postischemic basal release of
      nitric oxide by endothelium, as assessed by the percentage loss of coronary flow
      in response to 0.5 mmol/L L-monomethylarginine, an inhibitor of nitric oxide
      synthase, was as follows: (mean +/- standard error of the mean): 87.1% +/- 1.7%,
      81.2% +/- 2.3%, 79.6% +/- 1.9%, and 74.9% +/- 2.4% in groups 1, 2, 3, and 4,
      respectively. Stimulated release of nitric oxide, as assessed by percentage
      increase of coronary flow to 10(-5) mmol/L 5-hydroxytryptamine, an endothelium
      dependent vasodilator, was as follows (mean +/- standard error of the mean):
      88.3% +/- 1.5%, 83.4% +/- 2.4%, 71.1% +/- 2.7%, and 63.1% +/- 3.3% in groups 1,
      2, 3, and 4, respectively. Significant differences were found between each group
      (p < 0.05) for both basal and stimulated release of nitric oxide. Vascular smooth
      muscle function, as assessed by the percentage increase in coronary flow in
      response to glyceryl trinitrate, an endothelium-independent vasodilator, was
      (mean +/- standard error of the mean): 96.7% +/- 2.1%, 92.3% +/- 5.2%, 92.9% +/-
      5.0%, and 98.1% +/- 2.4% in groups 1, 2, 3, and 4 respectively. No significant
      difference was found between groups (p = not significant). In a protocol
      mimicking conditions for transplantation, the postischemic recovery of the basal
      and stimulated release of nitric oxide, but not vascular smooth muscle function,
      diminished with age.

PMID- 8551772
TI  - Cardiac gene transfer by intracoronary infusion of adenovirus vector-mediated
      reporter gene in the transplanted mouse heart.
AB  - This study introduces a model for intracoronary gene transfer in murine cardiac
      isografts using adenovirus vectors. This approach may offer an opportunity to
      modulate alloreactivity after cardiac transplantation. Donor hearts were infected
      via the coronary arteries with a volume of 10(9) plaque-forming units per
      milliliter of a recombinant adenovirus containing the beta-galactosidase-encoding
      gene (Ad.CMVLacZ). In a control group, 200 microliters of normal saline solution
      was infused. The grafts were stored in 4 degrees C cold saline solution for 15
      minutes, then transplanted heterotopically into syngeneic hosts (B10.BR). The
      grafts were harvested at 3, 7, 15, or 30 days (n = 5 for each group) after
      transplantation, and beta-galactosidase activity was assessed by histochemical
      staining (X-gal). All grafts were functioning when harvested. X-gal staining
      pattern was nonuniform with positive staining appearing in epicardial,
      myocardial, and endocardial cells, as well as in the vessel walls. The cells
      permissive to infection consisted predominantly of myocardial cells. The mean
      total numbers of beta-gal-positive staining cells per slice were 68.7 +/- 27.3 in
      the 3-day group, 330.4 +/- 53.8 in the 7-day group, 151.3 +/- 48.0 in the 15-day
      group, and 39.9 +/- 10.8 in the 30-day group, thus peaking in the 7-day group (p
      < 0.05). Control isografts (n = 5), retrieved at day 30, revealed no staining
      activity. In conclusion, our model demonstrates that intracoronary gene transfer
      to the transplanted murine cardiac grafts is feasible at the time of harvest.
      Adenovirus-mediated gene transfer produces widespread gene expression which,
      though perhaps transient, does not adversely affect myocardial structure or
      function. This technology may allow modification of graft immunogenicity in the
      future through the production of therapeutic proteins sufficient to modulate
      local immune responses.

PMID- 8551773
TI  - Increased levels of endothelin-1 in bronchoalveolar lavage fluid of patients with
      lung allografts.
AB  - The aim of the present study was to determine levels of endothelin-1 in
      bronchoalveolar lavage fluid and in plasma in patients with lung and heart-lung
      allografts. The aim was based on the hypothesis that levels of endothelin-1 are
      elevated in the bronchoalveolar lavage fluid of patients with lung allografts.
      Patients (n = 23) undergoing heart-lung (n = 8), single-lung (n = 10), or
      bilateral lung (n = 5) transplantation were included in the study. In patients
      with single-lung allografts, endothelin-1 levels were analyzed in bronchoalveolar
      lavage fluid from both the transplanted and the nontransplanted, native lung. The
      level of endothelin-1 was also analyzed in bronchoalveolar lavage fluid from 12
      patients who did not undergo transplantation. Transbronchial biopsies and
      bronchoalveolar lavage were done routinely or when clinically indicated on 64
      different occasions, between 2 and 104 weeks after transplantation. The level of
      endothelin-1 was measured in bronchoalveolar lavage fluid and plasma by
      radioimmunoassay. Immunoreactive endothelin-1 was detectable in bronchoalveolar
      lavage fluid from all patients. The concentration of endothelin-1 in
      bronchoalveolar lavage fluid from transplanted lungs (2.94 +/- 0.30 pg/ml, n =
      64) was significantly higher compared with that in bronchoalveolar lavage fluid
      from patients without allografts (0.86 +/- 0.20 pg/ml, n = 12, p < 0.01). In
      patients who received single-lung transplantation because of emphysema, the level
      of endothelin-1 in bronchoalveolar lavage fluid from the transplanted lung was
      significantly greater than that from the native lung (5.61 +/- 1.9 versus 0.39 +/
      0.05 pg/ml, p < 0.05). Concentrations of endothelin-1 in bronchoalveolar lavage
      fluid did not correlate with grade of rejection, infection, or time after
      transplant. Plasma levels of endothelin-1 were unchanged with pulmonary
      rejection. These results indicate that endothelin-1 is released into bronchi of
      transplanted human lungs. The release is not associated with rejection or
      infection. Because of its potent mitogenic properties, endothelin-1 may have a
      potential impact in the development of posttransplant complications such as
      bronchiolitis obliterans.

PMID- 8551775
TI  - Cerebral hyperthermia during cardiopulmonary bypass in adults.

PMID- 8551774
TI  - delta Opioid extends hypothermic preservation time of the lung.
AB  - To test the hypothesis that a delta opioid, DADLE ([D-Ala2, D-Leu5]-enkephalin),
      could protect tissue from ischemic damage during hypothermic lung preservation,
      we studied three groups of rats. In group 1 (n = 8), lung function was studied
      immediately after harvesting. In group 2 (n = 8), the lung was flushed with 4
      degrees C Euro-Collins solution and preserved for 24 hours. In group 3 (n = 8),
      the lung was flushed with 4 degrees C Euro-Collins solution plus DADLE (1 mg/kg)
      and preserved for 24 hours. Lung function was studied by using a living rat
      perfusion model. Venous blood from the host rat perfused the pulmonary artery of
      the isolated lung. Blood from the isolated lung was returned to the carotid
      artery of the host rat with a roller pump. Severe pulmonary edema, hemorrhage,
      and occlusive pulmonary artery resistance occurred in group 2 within 30 minutes
      of perfusion. Perfusion studies were carried out for more than 60 minutes in
      groups 1 and 3. Pulmonary blood flow was lower in group 2 than in either group 1
      or group 3. Pulmonary vascular resistance was much higher in group 2 than in
      groups 1 and 3 (p < 0.05). Airway pressure and airway resistance were much higher
      in group 2 than in groups 1 and 3 (p < 0.05). Airway resistance was also higher
      in group 3 than in group 1 after 20 minutes of perfusion (p < 0.05). Oxygen
      tensions from the pulmonary vein of the isolated lung in group 2 were lower than
      those in groups 1 and 3 (p < 0.05). Alveolar-arterial oxygen difference was much
      higher in group 2 than in groups 1 and 3 (p < 0.05). Lung tissue wet/dry weight
      ratio after perfusion was much higher in group 2 than in groups 1 and 3. The
      results clearly show, for the first time, that DADLE can effectively enhance
      hypothermic lung preservation in rats.

PMID- 8551776
TI  - Retrograde perfusion through the superior vena cava perfuses the brain in human
      beings.

PMID- 8551777
TI  - Retransfusion of thoracic wound blood during heart surgery obscures
      biocompatibility of the extracorporeal circuit.

PMID- 8551778
TI  - Successful repair of postinfarction left ventricular free wall rupture: new
      strategy with hypothermic percutaneous cardiopulmonary bypass.

PMID- 8551779
TI  - Valvular (external hinge) leakage of the CarboMedics mitral valve.

PMID- 8551780
TI  - Video-assisted observation in mitral valve surgery.

PMID- 8551781
TI  - Transvalvular technique for implantation of a mitral valve homograft.

PMID- 8551782
TI  - Hazards of administering blood cardioplegic solution directly into the heart:
      cardioplegic solutions are not equal.

PMID- 8551783
TI  - Nitric oxide: unjustified credit?

PMID- 8551784
TI  - Valved atrial septal patch.

PMID- 8551785
TI  - Monofilament polypropylene sutures in aortic valve replacement.

PMID- 8551787
TI  - Retrograde brain perfusion beyond the venous values. Hemodynamics and
      intracellular pH mapping.
AB  - Twenty-one dogs (group 1) had retrograde brain perfusion for 90 minutes through
      the sagittal sinus and superior vena cava with pressure-regulated cardiopulmonary
      bypass, and 10 dogs (group 2) had 60 minutes of circulatory arrest with an
      additional 30-minute evaluation of brain slices, both at 20 degrees C. In group
      1, cerebral blood flow determined by laser flowmetry was 8.98 +/- 2.02 ml/100
      gm/min with a driving pressure of 29.69 +/- 9.92 mm Hg during the retrograde
      perfusion, whereas it was 0.85 ml/100 gm/min during solitary perfusion through
      the superior vena cava. Retrograde cerebral vascular resistance was slightly
      higher than the antegrade resistance. Neutral red stain was given
      intraperitoneally as an intracellular pH indicator. Regional intracellular pH was
      calculated from photoabsorption at 440 and 535 nm with the use of color
      transparency photographs of the brain and spinal cord slices taken after
      retrograde cerebral perfusion in group 1 and after circulatory arrest in group 2.
      The pH mapping showed that the retrograde brain perfusion maintained the pH
      within 6.77 to 7.14, whereas the cerebral pH decreased to 6.24 to 6.43 at 60
      minutes of circulatory arrest and further decreased to 5.81 to 6.22 at 90
      minutes. The pH after the retrograde brain perfusion was significantly higher
      than the pH after circulatory arrest in the entire brain and the spinal cord. We
      conclude that the brain is protected when perfused retrogradely beyond the venous
      valves with a driving pressure above 20 mm Hg.

PMID- 8551786
TI  - Attenuation of cardiopulmonary bypass-derived inflammatory reactions reduces
      myocardial reperfusion injury in cardiac operations.
AB  - In cardiac operations endopeptidase (protease) inhibitor may be beneficial in
      reducing myocardial injury when administered in the cardiopulmonary bypass prime.
      Nafamostat mesilate was evaluated in 20 patients who underwent coronary artery
      bypass grafting. The patients were divided into a control group (n = 10) and a
      nafamostat group (n = 10). Nafamostat (2 mg/kg per hour) was continuously given
      during cardiopulmonary bypass in the nafamostat group. The age, number of grafts,
      cardiopulmonary bypass time, and aortic crossclamp time were similar between
      groups. In the control group, neither tumor necrosis factor-alpha nor interleukin
      1 levels showed any significant change during cardiopulmonary bypass, whereas
      interleukin-6 and interleukin-8 levels, percent expression of adhesion molecule
      (CD18) on neutrophils, and CH50 assay results increased significantly during
      cardiopulmonary bypass. As compared with the control group, the nafamostat group
      showed significantly lower levels of interleukin-6 (123 +/- 57 versus 40 +/- 22
      pg/ml, respectively) and interleukin-8 (96 +/- 13 versus 66 +/- 14 pg/ml,
      respectively). The nafamostat group showed a significantly lower difference of
      CH50 assay results and malondialdehyde levels between coronary sinus blood and
      arterial blood and peak values of creatine kinase MB (43 +/- 12 IU/L versus 19 +/
      6 IU/L) during the postoperative course compared with findings in the control
      group. These results demonstrated that inflammatory reactions induced by
      cardiopulmonary bypass had adverse effects on myocardial recovery after aortic
      crossclamping and that nafamostat mesilate given during cardiopulmonary bypass
      appeared to reduce myocardial reperfusion injury by attenuating such inflammatory
      reactions. Attenuation of inflammatory reactions of cardiopulmonary bypass should
      be considered in the strategy of myocardial protection.

PMID- 8551788
TI  - Leukocyte and platelet depletion with a blood cell separator: effects on lung
      injury after cardiac surgery with cardiopulmonary bypass.
AB  - This study was undertaken to assess the effects of leukocyte and platelet
      depletion on postoperative lung injury in 42 patients who underwent heart
      operations. Blood was serially sampled before, during, and after cardiopulmonary
      bypass, and leukocyte count, platelet count, and thromboxane B2 6-keto-PGF1
      alpha, leukocyte elastase, thrombin-antithrombin III complex, and D-dimer levels
      were determined. Postoperative respiratory function was assessed based on
      analyses of oxygenation and carbon dioxide elimination. Leukocyte and platelet
      depletion was performed in 21 patients (experimental group) but not in another
      (control group). In the experimental group, leukocytes and platelets were removed
      continuously by means of the blood cell separator CS-3000, beginning immediately
      after the start of the operation and ending 1 hour after the release of aortic
      occlusion. Leukocyte elastase, thromboxane B2, ratio of thromboxane B2 to 6-keto
      PGF1 alpha, thrombin-antithrombin III complex, and D-dimer were significantly
      lower in the experimental group than in the control group. Of the various indexes
      of oxygenation, arterial oxygen tension was significantly higher in the
      experimental group and the alveolar-arterial oxygen pressure difference and
      respiratory index were significantly lower in the experimental group. The
      positive end-expiratory pressure needed to achieve an appropriate arterial oxygen
      tension was significantly lower in the experimental group. The elimination of
      carbon dioxide was lower in the experimental group. Depletion of leukocytes and
      platelets reduced respiratory dysfunction after heart operations with
      cardiopulmonary bypass. It was particularly effective in patients with a low
      preoperative oxygenation capacity and in those for whom an extended period of
      cardiopulmonary bypass was required.

PMID- 8551789
TI  - A valveless high stroke volume counterpulsation device restores hemodynamics in
      patients with congestive heart failure and intractable cardiogenic shock awaiting
      heart transplantation.
AB  - The paraaortic counterpulsation device is a round pumping chamber with one
      valveless opening 20 mm in diameter and a 100 ml stroke volume. The paraaortic
      counterpulsation device was implanted on the ascending aorta of three male
      patients with intractable cardiogenic shock. Patients were assisted for 4 hours
      and 8 and 54 days, respectively; the first patient died as a result of
      nonresponding peripheral vasodilation and the other two died of septic shock. The
      two patients who were assisted for 8 and 54 days were conscious and able to
      function in a limited manner during the mechanical assistance. Discontinuation of
      the mechanical support for a few seconds was followed by low systolic arterial
      pressure (30 to 60 mm Hg) and syncopal episodes. Biochemical tests and autopsy
      results in these patients showed no evidence of blood cell destruction, thrombus
      formation, brain infarction, or other distal emboli. In conclusion, satisfactory
      hemodynamic effects, excellent biocompatibility, and simplicity of the
      implantation procedure in these patients encourage the use of the paraaortic
      counterpulsation device as a bridge to heart transplantation.

PMID- 8551790
TI  - Bypass conduit vessel wall biology substantially influences downstream myocardial
      contractile response to injury from ischemia and reperfusion.
AB  - Coronary vascular intraluminal release of endogenous endothelium-derived
      substances, such as prostacyclin, may affect downstream cardiac myocyte
      contractile function. With a "chronic" canine model of endothelialized and
      deendothelialized internal thoracic artery coronary grafts, we tested the
      hypothesis that higher basal release of endothelium-derived prostacyclin in
      internal thoracic artery bypass conduit effluent accelerates functional recovery
      of postischemic stunned myocardium in the intact circulation. Eleven dogs
      underwent left internal thoracic artery-left circumflex artery bypass, and the
      proximal circumflex artery was then ligated. Internal thoracic artery conduit
      endothelium was denuded by balloon catheter in five dogs before grafting and left
      intact in six dogs. After 7 days, awake dogs were studied to measure myocardial
      segment length in the circumflex region with ultrasonic dimension transducers,
      left ventricular pressure with micromanometers, and circumflex artery flow with
      an ultrasonic flow probe. Regional contractile function was quantified by the
      area beneath the linear preload recruitable stroke work relationship at baseline
      and at intervals after a 15-minute circumflex graft occlusion followed by 3 hours
      of reperfusion. Heart rate, left ventricular peak pressure, left ventricular end
      diastolic pressure, left ventricular peak first derivative of pressure (dP/dt),
      and circumflex flow were similar (all p not significant) in endothelialized and
      nonendothelialized dogs during ischemia and reperfusion. Ischemia reduced the
      preload recruitable stroke work relationship to 44% +/- 35% of control values (p
      < 0.01) in endothelialized dogs and to 47% +/- 18% of control values in
      nonendothelialized dogs (p < 0.01) at 15 minutes of reperfusion, indicating a
      similar (p not significant) initial degree of injury. During 3 hours of
      reperfusion, the preload recruitable stroke work relationship returned to 51% +/-
      17% of control values in endothelialized dogs but to only 35% +/- 20% of control
      values in nonendothelialized dogs (p < 0.02). Basal intraluminal release of
      endogenous prostanoids in excised internal thoracic artery conduits was
      subsequently quantified by ex vivo bioassay of vasoactive properties of conduit
      effluent on normal coronary artery smooth muscle. Endothelialized conduits
      induced greater smooth muscle relaxation than did nonendothelialized conduits
      (67% vs 23%), and this increased relaxation by endothelialized conduits was
      eliminated by indomethacin, a blocker of prostanoid synthesis. These data
      indicate that coronary bypass conduit endothelium-derived substances, such as
      prostacyclin, significantly influence downstream myocardial contractile response
      to ischemia and reperfusion, independent of alterations in coronary flow in the
      intact circulation.

PMID- 8551791
TI  - Improvement in functional recovery of the isolated guinea pig heart after
      hyperkalemic reperfusion with adenosine.
AB  - The aim of this study was to examine the effect of initial hyperkalemic
      reperfusion (HKR), with and without added adenosine, on coronary flow, myocardial
      function, and endothelium-dependent and endothelium-independent coronary vascular
      function. Cardioplegic arrest was induced in 40 isolated guinea pig hearts by
      infusing oxygenated cardioplegic (high in potassium ion) Krebs solution for 5
      minutes. Hearts were then stored at room temperature for 3.5 hours. On
      reperfusion, hearts were divided into four groups of 10 hearts each: control,
      reperfusion with regular Krebs solution (4.6 mmol/L potassium chloride); base
      hyperkalemic reperfusion, initial reperfusion with 37 degrees C oxygenated,
      cardioplegic Krebs solution for 5 minutes; hyperkalemic reperfusion with addition
      of 1 mmol/L adenosine during HKR; and hyperkalemic reperfusion with addition of 5
      mmol/L adenosine. Coronary reserve (adenosine bolus 2 mmol/L) and responses to
      acetylcholine (1 mumol/L) and nitroprusside (100 mumol/L) were examined before
      and after ischemia and reperfusion. Flow did not return to preischemic values in
      any group after reperfusion. Adenosine treatment during initial reperfusion
      increased coronary flow (percentage of baseline +/- standard error of the mean)
      from 57% +/- 4% in control and 45% +/- 3% in hearts with hyperkalemic reperfusion
      to 79% +/- 3% and 83% +/- 5% in hearts with hyperkalemic reperfusion also treated
      with, respectively, 1 mmol/L adenosine and 5 mmol/L adenosine (p < 0.05). At 30
      and 60 minutes of reperfusion, however, flow remained elevated only in the group
      treated with 5 mmol/L adenosine. Coronary reserve and responses to acetylcholine
      and nitroprusside were equivalently depressed in all groups after reperfusion.
      Recovery of left ventricular systolic and diastolic function was improved in all
      groups after hyperkalemic reperfusion (54% +/- 4% of preischemic value) compared
      with control (39% +/- 3%), and recovery was further enhanced in the group treated
      with 5 mmol/L adenosine (60% +/- 4%). In this ex vivo model, hyperkalemic
      reperfusion improved myocardial function after cardioplegic arrest and the
      addition of 5 mmol/L adenosine improved coronary flow. Adenosine may counteract
      the potassium chloride-induced vasoconstriction that occurs during hyperkalemic
      reperfusion and may thus improve coronary flow and myocardial function.
      Postischemic depression of endothelium-dependent or endothelium-independent
      vascular functions, however, was not alleviated by hyperkalemic reperfusion with
      or without adenosine.

PMID- 8551792
TI  - Tumors of the esophagogastric junction. Long-term survival in relation to the
      pattern of lymph node metastasis and a critical analysis of the accuracy or
      inaccuracy of pTNM classification.
AB  - From 1983 to 1989, 95 patients with carcinoma of the esophagogastric junction
      underwent resection. Overall hospital mortality rate was 6.2% (6/95). Actuarial
      survival analysis showed 5- and 10-year survivals of 33% and 31%, respectively.
      Five- and 10-year survivals of patients according to TNM stages were as follows:
      stage I (n = 13), 90% at both 5 and 10 years; stage II (n = 13), 70% at both
      intervals; stage III (n = 28), 28% at both intervals; and stage IV (n = 40), 11%
      and 8%, respectively. For patients with undiseased nodes (n = 26), 5- and 10-year
      survivals were 72% and 72%, compared with 18% and 16% for patients with diseased
      nodes (n = 68; p < 0.005). In patients who had involvement of both the abdominal
      and thoracic lymph nodes (n = 28), 5- and 10-year survivals were 13% and 13%,
      compared with 26% and 26% if metastases were confined to the abdomen (n = 37; p >
      0.05). Grouping patients with diseased intrathoracic nodes together with patients
      with N2 abdominal nodes showed survivals of 14% at both 5 and 10 years. When
      tumors were staged as an esophageal carcinoma, classification of individual
      patients changed, as did the 5- and 10-year survivals. Five- and 10-year
      survivals were as follows: stage I (n = 8), 100% for both 5 and 10 years; stage
      II (n = 18), 68% for both 5 and 10 years; stage III (n = 27), 37% for both 5 and
      10 years; and stage IV (n = 41), 10% for 5 years and 6% for 10 years. These data
      indicate that tumors of the esophagogastric junction tend to spread to both
      abdominal and thoracic nodes. However, reasonably good 5- and 10-year survivals
      can be obtained even in patients with nodal metastases in both areas. We suggest
      that N2 labeling be included for thoracic node metastases instead of the actual
      M+Ly label, because the N2 label better reflects the potential for curative
      surgery. Finally, staging tumors as gastric or esophageal carcinoma makes no
      significant difference in survival analysis, which raises the question whether
      these tumors behave more like esophageal carcinoma than gastric carcinoma.

PMID- 8551793
TI  - Predictors of survival in malignant tumors of the sternum.
AB  - From 1930 to 1994, 54 patients with primary malignant tumors of the sternum were
      seen. Fifty patients were first seen with a mass, and one half of them also had
      pain in the sternal region. Two patients had no symptoms at presentation. Among
      39 solid tumors were 26 chondrosarcomas, 10 osteosarcomas, 1 fibrosarcoma, 1
      angiosarcoma, and 1 malignant fibrous histiocytoma. Of these, 25 were low-grade
      and 14 were high-grade tumors. Among 15 small cell tumors were 8 plasmacytomas, 6
      malignant lymphomas, and 1 Ewing's sarcoma. Partial or subtotal sternectomy was
      done in 37 patients and total sternectomy in 3. Of the remaining 14 patients, 3
      had local excision; 10 had external radiation or chemotherapy without operation,
      or both; and 1 had no treatment. All but one patient treated by wide resection (N
      = 40) had some form of skeletal reconstruction of the chest wall defect. Thirty
      one (78%) underwent repair with Marlex mesh, and in 25 this was combined with
      methyl methacrylate. The skin edges were closed per primum in 32 patients; 8
      required muscle, omentum, or skin flaps. Resection in chondrosarcomas yielded a 5
      year survival (Kaplan-Meier) of 80% (median follow-up, 17 years). The 5-year
      survival in osteosarcomas was 14%. Resection was curative in 64% of low-grade
      sarcomas but in only 7% of high-grade sarcomas. In small cell tumors, resection
      and radiation were helpful for local control; all failures were a result of
      distant metastases. We conclude that primary sarcomas of the sternum though
      uncommon are potentially curable by wide surgical excision. With rigid prostheses
      to repair the skeletal defects, the surgical complication rates are low. Overall
      survival after complete surgical resection is related to tumor histologic type
      and grade.

PMID- 8551794
TI  - The water-insoluble camptothecin analogues: promising drugs for the effective
      treatment of haematological malignancies.
AB  - After failing to exhibit benefits in clinical studies with cancer patients in the
      early 1970s, camptothecin (CPT) and its water-insoluble analogues are re-emerging
      as promising drugs with multiple actions in the treatment of human haematological
      malignancies. CPT analogues interfere with the mechanism of action of the nuclear
      enzyme topoisomerase I, while the cells progress through the S-phase of the cell
      cycle and this results in cell death by apoptosis. Modulations of topoisomerase I
      phosphorylation may indirectly modulate the cytotoxic activity of CPT analogues.
      In vitro, CPT analogues have exhibited increased or unaltered killing activity
      against leukaemia cells resistant to epipodophyllotoxins, anthracyclines,
      anthracenediones, and Vinca alkaloids, while development of resistance to CPT
      analogues renders leukaemia and lymphoma cells more sensitive to topoisomerase II
      directed drugs, inducers of cell differentiation, and immunotoxins. Oral
      administration of the CPT analogues has circumvented the inconvenience of
      solubility of these drugs. Metabolic conversion of the CPT analogue 9-nitro-CPT
      to equally or more potent 9-amino-CPT practically makes unnecessary treatment of
      the patient with 9-amino-CPT, which, in addition, is costlier to prepare than 9
      nitro-CPT. Considering the therapeutic, economic and handling viewpoints, the
      overall conclusion is that the water-insoluble CPT analogues are very promising
      antileukaemia/antilymphoma agents that warrant further preclinical and clinical
      studies.

PMID- 8551795
TI  - Selective inhibitors of 5-lipoxygenase reduce CML blast cell proliferation and
      induce limited differentiation and apoptosis.
AB  - Inhibitors of the arachidonic acid metabolizing enzyme, 5-lipoxygenase, reduce
      the rate of proliferation of chronic myelogenous leukemia blast cells. The
      inhibitory agents studied were ETYA, A63162 and SC41661A. These reagents induced
      differentiation of cultured chronic myelogenous leukemia cells from blast to
      promyelocytic morphology. Promyelocytic cells then underwent apoptosis, which was
      identified by nuclear and cytoplasmic morphological features and by DNA
      laddering. Proliferation of monoblastoid U937 and myelomonocytic HL60 cell lines,
      known to contain 5-lipoxygenase and synthesize leukotrienes, was reduced by these
      inhibitors. U937 cells cultured with ETYA, A63162 or SC41661A for 48 h exhibited
      apoptosis as assessed by DNA laddering and morphology. Characteristic
      ultrastructural changes of apoptosis were seen at 120 h. MK886, an inhibitor of 5
      lipoxygenase with a mechanism of action distinct from oxidation/reduction
      reagents, at 20-40 microM also inhibited CML and U937 cell proliferation and
      induced apoptosis, as shown by DNA laddering and ultrastructure.

PMID- 8551796
TI  - Potentiation of tumor necrosis factor-mediated cytotoxicity on human myeloid cell
      lines: effects of interferons versus dimethylsulphoxide.
AB  - After prolonged incubation times of 72 h IFN alpha 2a and IFN beta 1
      significantly reduced cell growth in the myelomonocytic U937 and THP1 cell lines.
      IFN gamma showed only slight growth inhibitory activities. IFN activities were
      potentiated by the highly polar differentiation inducer dimethylsulphoxide, which
      is similar to our previous study on tumor necrosis factor (TNF). However, in
      contrast with TNF, none of the interferon types induced cell cytotoxicity or DNA
      fragmentation. Like DMSO, all interferons potentiated TNF-induced cytotoxicity,
      IFN beta 1 and IFN gamma being the most potent in this respect. When applied
      together, DMSO and IFN gamma enhanced TNF-mediated cell lysis in either an
      additive (in the case of U937, THP1, HL60 cells) or a synergistic (in the case of
      KG1) manner, suggesting that the mechanisms of the potentiating activity of DMSO
      and IFN gamma are different. The potential role of the simultaneous use of DMSO
      related molecules, and TNF and/or IFN in leukemic cancer chemotherapy is
      discussed.

PMID- 8551797
TI  - Aberrant progenitors common to megakaryocytic and myeloid cells in a Down's
      infant with transient abnormal myelopoiesis.
AB  - Phenotypic characteristics of blasts were studied in a Down's infant with
      transient abnormal myelopoiesis (TAM). Two major subpopulations were identified:
      (1) CD33+CD42b+ cells with platelet peroxidase activity, the commitment of which
      to megakaryocytic lineage was supported by an increased expression of GATA-1
      mRNA; (2) CD33+CD34+CD7+CD4+ cells with immature ultrastructure, which could be
      either immature megakaryocytic or myeloid cells with aberrant differentiation.
      Mixed colonies containing megakaryocytes and monocyte/macrophages in the
      peripheral blood suggested the presence of progenitors common to these
      subpopulations. These results may indicate that subpopulations of blasts with
      phenotypic diversity could be derived from aberrant common progenitors to
      megakaryocytic and myeloid lineages in this patient.

PMID- 8551798
TI  - Establishment and characterization of a villous lymphoma cell line from splenic B
      cell lymphoma.
AB  - A new B-cell line (VL51) with cytoplasmic villi was established from a female
      patient with splenic lymphoma with circulating villous lymphocytes (SLVL). The
      patient exhibited a clinical picture characteristic of SLVL, including massive
      enlargement of the spleen. Tartrate-resistant acid phosphatase (TRAP)-negative
      villous lymphocytes were seen in the peripheral blood, bone marrow (BM) and both
      red and white pulps of the spleen. Monoclonality of the VL51 cell line was
      confirmed by clonal genotype abnormalities in the immunoglobulin heavy chain
      (IgH) gene and the T-cell receptor beta (TCR beta) gene. Evidence for commitment
      of phenotype of the VL51 cell line to the B lineage was also shown by the
      immunophenotype, including expression of CD10, CD19, CD20 and surface
      immunoglobins. The VL51 cells were positive for Epstein-Barr virus nuclear
      antigen (EBNA). The VL51 cell line is the first SLVL cell line to be established,
      and it is expected to be useful in clarifying the leukemogenesis of SLVL.

PMID- 8551799
TI  - Beta-tubulin and P-glycoprotein: major determinants of vincristine accumulation
      in B-CLL cells.
AB  - Vincristine (VCR) accumulation in chronic lymphatic leukemia of B-cell origin (B
      CLL) has recently been shown not to be inversely correlated to P-glycoprotein
      (PGP) levels. Therefore, we studied, in addition to PGP expression and
      accumulation of VCR, the cellular beta-tubulin content in quiescent and rhIL-2
      activated B-CLL cells. VCR mediates cytotoxicity by binding to tubulin.
      Constitutive beta-tubulin levels in B-CLL cells varied considerably. Upon
      activation with rhIL-2, beta-tubulin expression increased significantly.
      Therefore, tubulin levels could be correlated over a wide range to VCR
      accumulation. When the PGP-mediated drug efflux was blocked by verapamil (VRP),
      tubulin levels correlated linearly to VCR accumulation. All B-CLL cases expressed
      PGP at different levels. There was no linear correlation between PGP expression
      and VCR accumulation. A modulation factor m was defined as a quotient of VCR
      accumulation in the presence and absence of VRP to define the extent by which VRP
      inhibited a steady-state accumulation of VCR. The factor allowed discrimination
      between B-CLLs expressing low versus high PGP, irrespective of the levels of
      tubulin. However, PGP and beta-tubulin levels together were predictive for VCR
      accumulation in steady state. There was no uniform-accumulation defect for VCR in
      B-cell CLL because beta-tubulin and PGP were expressed independently. Non PGP
      mediated VCR transport seems to play a minor role in B-cell CLL. Leukemia
      associated varying of cytoskeletal organization in B-cell CLL might be one reason
      for the diverse cellular responses to receptor-mediated signals.

PMID- 8551800
TI  - Differential effect of heat shock on RNA metabolism in human Burkitt's lymphoma B
      cell lines.
AB  - Thermal stress induces expression of a family of heat shock proteins which may
      regulate the synthesis of various cellular genes. We investigated the effect of
      heat shock on polyadenylation in Epstein-Barr Virus (EBV) negative and EBV
      transformed human Burkitt's lymphoma (BL) B-cell lines. Incubation of the BL B
      cell line P3HR-1, carrying the defective EBV genome [EBV nuclear antigen-2 gene
      deletion] at 46 degrees C for 15 min increased nuclear poly(A) polymerase (PAP)
      activity. Thereafter, enzymatic activity declined and at 60 min it was reduced to
      about 50% of that observed in cells incubated at 37 degrees C. In contrast, no
      significant increase in PAP activity was observed at 15 min or thereafter in an
      EBV- BL cell line, ST-486, in response to elevated temperature. Furthermore, no
      heat shock mediated change in nuclear poly(A)-specific endonuclease activity was
      observed in either P3HR-1 or ST-486 cells suggesting a specific effect on PAP
      activity. However, thermal stress dependent increase in c-myc expression was
      detected only in P3HR-I cells. These results suggest an association between EBV
      transformation and enhanced expression of c-myc and PAP activity. To further
      determine the role of EBV, and EBV- BL cell line, BL-30, and BL-30 cells infected
      in vitro with a wild type strain of EBV, BL-30/B95-8, were investigated. BL-30/B
      95-8, unlike the parental BL-30 cells, exhibited c-myc and PAP gene upregulation
      at 15 min but were downregulated at 60 min following exposure of cells to
      elevated temperatures. These results suggest that infection of human B-cells with
      EBV is associated with their ability to respond to thermal stress by increased
      PAP activity which may stabilize mRNA through enhanced polyadenylation.

PMID- 8551801
TI  - Myelomonocytic antigens in B-cell chronic lymphocytic leukemia.
AB  - The clinical significance of myelomonocytic (MyMo) antigens in B-cell chronic
      lymphocytic leukemia (B-CLL) is unclear. We have analyzed the expression of MyMo
      antigens (CD13, CD14 (LeuM3, My4, Mo2), CD15, CD11b, CD11c, CD33 and CD68) on B
      lymphocytes (CD19+) in 105 B-CLL patients and in 35 controls. A double direct
      staining technique and flow cytometric analysis was performed. The expression of
      MyMo antigens on the control group did not exceed 4% B-lymphocytes. A MyMo
      antigen was considered as positive when present in > or = 10% of B-lymphocytes.
      Among the B-CLL patients, 28 (26.7%) were positive for CD11c, 21 (20.0%) for
      CD11b, nine (8.6%) for CD15, five (4.8%) for CD13, two (1.9%) for Mo2, and one
      (1.0%) for My4. No patient was positive for LeuM3, CD33 or CD68. CD11c was more
      frequently expressed in patients with a short lymphocyte doubling time (< 12
      months) (P = 0.05) and CD11b in the group with a higher number of lymphoid areas
      involved (P = 0.02). No correlation was found between lymphoid morphology and
      MyMo antigen expression. Fourteen of the 80 patients at risk subsequently
      progressed to a more advanced stage. Multivariate analysis identified hemoglobin
      (P = 0.004) and CD11b positivity (P = 0.009) as independent variables for disease
      progression. Fifteen patients died during evolution. Seven out of the 21 CD11b
      positive patients and eight of the 84 CD11b negative patients died (LR: P = 0.02,
      BG: P = 0.05). In the multivariate analysis, only CD11b positivity (> or = 10%)
      added prognostic value to clinical stages.

PMID- 8551802
TI  - Comparison of the induction of apoptosis in human leukemic cell lines by 2',2'
      difluorodeoxycytidine (gemcitabine) and cytosine arabinoside.
AB  - The induction of DNA fragmentation by cytosine arabinoside (araC) and 2',2'
      difluorodeoxycytidine (dFdC, gemcitabine) was compared in human leukemic cell
      lines. For both araC and dFdC this process was time- and concentration-dependent
      and resulted in loss of clonogenic survival of HL-60 myeloid leukemic cells.
      There was a marked difference in the potency between these two analogs in
      inducing apoptosis. A 6 h exposure to 5 microM araC was required to produce DNA
      laddering in HL-60 cells, whereas dFdC at a concentration 100-fold less (0.05
      microM) was sufficient to produce similar results. Pre-incubation of HL-60 cells
      with staurosporine, a non-specific protein kinase C inhibitor, increased the
      level of apoptosis induced by a 3 h exposure to araC or dFdC, suggesting the
      possible involvement of this family of enzymes in this process. Also, dFdC was
      able to increase the expression of both c-jun and c-fos in Molt-3 leukemic cells
      with a concentration known to induce apoptosis in this cell line.

PMID- 8551803
TI  - Chromosomal translocations in two feline T-cell lymphomas.
AB  - Two feline malignant lymphoma cell lines, FT-1 and FT-G, established from cats
      naturally infected with the feline leukemia virus were analyzed for chromosomal
      aberrations. Both FT-1 and FT-G cells had a modal number of 38 which is the
      normal diploid (2n) chromosome number of the domestic cat. G-banding-analysis
      showed that FT-1 had a translocation involving the short arms of chromosome A2
      and D3--t (A2;D3) (p-;p+), and FT-G had a translocation involving the short arms
      of chromosomes A2 and B2--t (A2;B2) (p-;p+). Our data suggest that the
      chromosomal translocations were closely associated with the tumorigenesis in
      malignant lymphoma in cats.

PMID- 8551804
TI  - Prognostic value of early response to chemotherapy assessed by the day 15 bone
      marrow aspiration in adult acute lymphoblastic leukemia: a prospective analysis
      of 437 cases and its application for designing induction chemotherapy trials.
AB  - The early response to induction chemotherapy assessed by the percentage of
      residual blast cells in the D15 bone marrow aspiration was prospectively
      evaluated in 437 patients included in the same multicentric trial of newly
      diagnosed adult acute lymphoblastic leukemia (LALA87). Among them, 286 patients
      (65.4%) had < or = 5% residual blasts and their complete remission (CR) rate at
      D28 was 91% while the CR rate at D28 was only 34% for the 151 patients (34.6%)
      with more than 5% blasts at D15 of the induction chemotherapy. The persistence of
      more than 5% of blasts was associated with a significantly worse overall survival
      (P < 0.0001) and worse disease-free survival (P = 0.02). These data are used as a
      support for simulating different strategies in order to improve CR rates in
      future clinical trials. Results are consistent with the fact that D15 marrow
      evaluation might be a relevant test allowing an early intensification of a
      subgroup of patients predicted to fail with conventional induction chemotherapy.

PMID- 8551805
TI  - Mutations of the p53 gene in myelodysplastic syndrome and overt leukemia.
AB  - We analysed p53 mutations in 24 patients with myelodysplastic syndrome (MDS) and
      overt acute myeloid leukaemia after a period of MDS, using polymerase chain
      reaction-single strand conformation polymorphism analysis. In exons 5 to 8,
      mobility shifts were detected in five of the 24 patients. Sequence analysis was
      subsequently performed, and four missense mutations (16.7%) and one silent
      nucleotide substitution were identified. Patients harbouring mutations were
      characterized as having advanced disease. Loss of the wild type allele was
      observed in three of the four patients with missense mutations. No mobility
      shifts of the N-ras or FMS gene were detected in these four patients. We next
      analysed the correlation of the p53 mutations with the progression of MDS in
      three patients. The mutation was accompanied by the progression in two of the
      three patients. These findings suggest that mutations of the p53 gene are
      associated with progression in some cases of MDS, while being compatible with
      stable disease or clonal evolution in others.

PMID- 8551806
TI  - Immunological subtypes of childhood acute lymphoblastic leukemia in Bulgaria.
AB  - With regards to the geographical variation in acute lymphoblastic leukemia (ALL)
      distribution, we present data from the immunophenotyping of 171 newly diagnosed
      cases of childhood ALL in Bulgaria during a 4 year period (1990-1994). On the
      basis of 17 phenotypic markers the distribution of immunological subtypes was as
      follows: AUL 4%; Pro-B ALL 13%; common ALL 42%; Pre-B ALL 11%; B-ALL 1%; T-ALL
      28% and unclassified 2%. Most of the cases were between 2 and 5 years of age.
      Common ALL was predominant (53%) in this age group. The male:female ratio was
      1.7:1. The frequency of T-ALL (28%) was significantly higher (P < 0.01; t = 3.49)
      in comparison to that reported for the U.S.A. and West European countries (mean
      13%). It was close to the frequency reported by some authors for France (20%),
      Greece (26%) and south Italy (28.1%). These countries and Bulgaria might form an
      environmental area with a moderate frequency of T-ALL.

PMID- 8551807
TI  - p16INK4 gene deletions in childhood acute lymphoblastic leukemias.

PMID- 8551808
TI  - Physician satisfaction with human immunodeficiency virus type 1 and hepatitis B
      virus testing in San Diego County.
AB  - Physician satisfaction with the laboratory testing process is one indicator of
      the physician's perception of the quality of laboratory testing and the
      effectiveness of the communication of the laboratory results. This study compares
      the level of satisfaction of physicians reporting their experience with human
      immunodeficiency virus type 1 (HIV-1) testing with the satisfaction levels of
      those physicians reporting their experience with hepatitis B virus (HBV) testing.
      By mail, 6,570 licensed San Diego County physicians were surveyed. Among those
      who tested for HIV-1 or HBV, their satisfaction with four different HIV-1 or HBV
      testing parameters was assessed: 1) specimen submission process, 2) test
      accuracy, 3) clarity of test report, and 4) turnaround time. Overall, physician
      satisfaction with both HIV-1 and HBV testing was high, particularly for test
      accuracy (means of 2.79 and 2.84, respectively on a 3-point scale), although
      slightly lower for turnaround time (means of 2.40 and 2.43, respectively). Mean
      satisfaction with the specimen submission process and test accuracy were higher
      for physicians who ordered HBV tests than for those who ordered HIV-1 tests.
      Satisfaction with the four HIV-1 testing process parameters varied significantly
      by physician specialty, practice type, and type of laboratory used. For HBV
      testing, significant differences were observed only for turnaround time. For both
      HIV-1 and HBV testing, those who received a final interpretation of laboratory
      results were more satisfied with test report clarity than those who did not.
      Although physician satisfaction with HIV-1 and HBV testing is high, this study
      identifies the least satisfied groups and specific areas in the testing process
      than may need improvement.

PMID- 8551809
TI  - Severity measurement methods and judging hospital death rates for pneumonia.
AB  - Payers and policymakers are increasingly examining hospital mortality rates as
      indicators of hospital quality. To be meaningful, these death rates must be
      adjusted for patient severity. This research examined whether judgments about an
      individual hospital's risk-adjusted mortality is affected by the severity
      adjustment method. Data came from 105 acute care hospitals nationwide that use
      the Medis-Groups severity measure. The study population was 18,016 adults
      hospitalized in 1991 for pneumonia. Multivariable logistic models to predict in
      hospital death were computed separately for 14 severity methods, controlling for
      patient age, sex, and diagnosis-related group (DRG). For each hospital, observed
      to-expected death rates and z scores were calculated for each severity method.
      The overall in-hospital death rate was 9.6%. Unadjusted mortality rates for the
      105 hospitals ranged from 1.4% to 19.6%. After adjusting for age, sex, DRG, and
      severity, 73 facilities had observed mortality rates that did not differ
      significantly from expected rates according to all 14 severity methods; two had
      rates significantly higher than expected for all 14 severity methods. For 30
      hospitals, observed mortality rates differed significantly from expected rates
      when judged by one or more but not all 14 severity methods. Kappa analysis showed
      fair to excellent agreement between severity methods. The 14 severity methods
      agreed about relative hospital performance more often than expected by chance,
      but perceptions of individual hospitals' mortality rates varied using different
      severity adjustment methods for almost one third of facilities. Judgments about
      individual hospital performance using different severity adjustment approaches
      may reach different conclusions.

PMID- 8551810
TI  - Determinants of rural hospital conversion. A model of profound organizational
      change.
AB  - One widely discussed response to the severe problems faced by many rural
      hospitals is to convert them into organizations that provide health services
      other than general, acute inpatient care. This study identifies conversions that
      occurred nationally from 1984 to 1991. The study also empirically examines the
      determinants of conversion, using rural hospitals that did not convert (between
      1984 and 1991) as a comparison group. The authors examine a set of factors that
      makes radical organizational change necessary (eg, poor performance) and reduces
      resistance to such change (eg, proximity to other hospitals). Results from
      discrete-time logistic regression show that converters are more likely than
      nonconverters to: have poor performance and fewer beds; be located very near to
      or very distant from similar hospitals; operate in larger communities; devote
      more of their care to areas other than acute inpatient care; and be members of
      multihospital systems. Converters also are less likely to be government owned.
      The need for future research on the effects of conversion is discussed.

PMID- 8551811
TI  - Health values of patients infected with human immunodeficiency virus.
      Relationship to mental health and physical functioning.
AB  - To assess the health values of patients infected with human immunodeficiency
      virus (HIV) and examine the relationships between their health values and health
      status at two points in time, the authors sought to determine whether patients'
      physical and mental health statuses were good predictors of how they valued their
      current state of health. One hundred thirty-nine patients with various stages of
      HIV infection were interviewed in a prospective cohort study based in a primary
      care practice of a community-based teaching hospital. Patients were interviewed
      twice at 6-month intervals using three health value measures--the time trade off,
      rating scale, and Quality of Well-being Scale--and three health status measures:
      the 18-item Mental Health Inventory, the Dyspnea-Fatigue Index, and the Medical
      Outcomes Study SF-36 Health Survey. The health status of HIV-infected patients
      was compromised and, with the exception of mental health, generally was worse
      among patients with more advanced HIV-infection. Rating scale and Quality of Well
      being Scale scores were related inversely to disease stage, but time-trade off
      scores generally were higher regardless of disease stage. Health value measures
      showed moderate relationships with measures of physical functioning (r = 0.34
      0.68) but only a fair relationship with mental health (r = 0.00-0.48). The health
      status of HIV-infected patients who remained asymptomatic or remained symptomatic
      but without developing acquired immunodeficiency syndrome (AIDS) changed little
      over 6 months, whereas the health status of patients with AIDS and of patients
      manifesting progression of HIV-infection deteriorated over time. In contrast,
      health values, particularly time-tradeoff scores, remained stable even in the
      face of changes in health status and disease progression. With the exception of
      mental health, the impact of HIV infection on health status tends to parallel the
      clinical stage of disease. Health values of HIV-infected patients, however,
      generally are high and correlate better with physical functioning than with
      mental health.

PMID- 8551812
TI  - Predictors of hepatitis B vaccine acceptance in health care workers.
AB  - This article examines the relative importance of occupational, epidemiologic, and
      attitudinal factors in hepatitis B vaccine acceptance. A stratified random sample
      of 1,018 health care workers at risk for occupational blood exposure at our
      university hospital were contacted in 1992 and 919 (90%) participated. Potential
      reasons for vaccine acceptance or refusal were evaluated with factor analysis.
      Logistic regression models were calibrated on a stratified random subsample to
      identify independent predictors of initiating and completing the series, then
      validated on the remaining subjects. Fifty-four percent (482 of 898) of
      previously nonimmune workers had completed the series, while 70% (626) had
      received one or more doses. Hepatitis B vaccine acceptance was related strongly
      to social influence (physicians, supervisors, role models, friends, and spouse)
      and knowledge of the disease and vaccine, whereas refusal was primarily related
      to concern about vaccine side effects and problems with vaccine access.
      Independent predictors of initiating the vaccine series included younger age
      (odds ratio [OR] 0.98 per year, 95% confidence interval [CI95] 0.96-0.997),
      occupation (housestaff: OR 2.9, CI95 1.1-7.9; nurses: OR 2.1, CI95 1.0-4.3 versus
      housekeepers), increased blood exposure frequency (OR 2.4, CI95 1.6-3.5 for 1-6
      versus 0 exposures in past year), and increased frequency of recent influenza
      vaccination (OR 3.3, CI95 2.0-5.3 for 1 versus 0 doses in prior 3 years).
      Occupation (increased acceptance among housestaff, nurses, nursing assistants,
      laboratory technicians), increased frequency of blood exposure, and recent
      influenza vaccination also were predictors of series completion. Factors such as
      occupation, blood exposure frequency and acceptance of other preventive services
      may help identify health care worker groups with low vaccine acceptance most
      likely to benefit from targeted vaccine delivery. Hepatitis B vaccine should be
      offered routinely during evaluation for occupational blood exposure. Future
      vaccine implementation efforts should emphasize the involvement of physicians and
      supervisors and education about occupational disease risk, liability, and the
      safety of the vaccine.

PMID- 8551813
TI  - Can comorbidity be measured by questionnaire rather than medical record review?
AB  - Comorbidity generally is measured by medical record abstraction, which is
      expensive and often impractical. The aim of this study was to assess the
      reproducibility and validity of a comorbidity questionnaire. The authors
      developed a brief comorbidity questionnaire that included items corresponding to
      each element of the medical record-based Charlson index. The questionnaire was
      administered to 170 inpatients. Charlson scores were abstracted from these
      patients' medical records. We assessed test-retest reliability of the
      questionnaire and the Charlson index, the correlation between the questionnaire
      and the Charlson index, and correlations between each comorbidity measure and
      indicators of health resource utilization including medication use,
      hospitalizations in the past year, and hospital charges. Test-retest reliability,
      assessed with the intraclass correlation coefficient, was 0.91 for the
      questionnaire and 0.92 for the chart-based Charlson index. The Spearman
      correlation between these two measures was 0.63. The correlation between
      comorbidity measures was weaker in less educated patients. Correlations with
      indicators of resource utilization were similar for the two comorbidity
      instruments. The authors found that a questionnaire version of the Charlson index
      is reproducible, valid, and offers practical advantages over medical record-based
      assessments.

PMID- 8551814
TI  - Overutilization of acute-care beds in Veterans Affairs hospitals.
AB  - The authors tested the hypothesis that the Department of Veterans Affairs (VA)
      hospitals would have substantial overutilization of acute care beds and services
      because of policies that emphasize inpatient care over ambulatory care. Reviewers
      from 24 randomly selected VA hospitals applied the InterQual ISD* (Intensity,
      Severity, Discharge) criteria for appropriateness concurrently to a random sample
      of 2,432 admissions to acute medical, surgical, and psychiatry services.
      Reliability of hospital reviewers in applying the ISD* criteria was tested by
      comparing their reviews with those of a small group of expert reviewers. Validity
      of the ISD* criteria was tested by comparing the assessments of master reviewers
      with the implicit judgments of panels of nine physicians. The physician panels
      validated the ISD* admission criteria for medicine and surgery (74% agreement
      with master reviewers, kappa > 0.4), whereas the psychiatry criteria were not
      validated (66% agreement, kappa 0.29). Hospital reviewers reliably used all three
      criteria sets (> 83% agreement with master reviewers, kappa > 0.6). Rates of
      nonacute admissions to acute medical and surgical services were > 38% as
      determined by the hospital and master reviewers and by the physician panels.
      Nonacute rates of continued stay were > 32% for both medicine and surgery
      services. Similar rates of nonacute admissions and continued stay were found for
      all 24 hospitals. Reasons for nonacute admissions and continued stay included
      lack of an ambulatory care alternative, conservative physician practices, delays
      in discharge planning, and social factors such as homelessness and long travel
      distances to the hospital. Using criteria that the authors showed to be reliable
      and valid, substantial overutilization of acute medicine and surgical beds was
      found in a representative sample of VA hospitals. Correcting this situation will
      require changes in physician practice patterns, development of ambulatory care
      alternatives to inpatient care, and modification of current VA policies
      determining eligibility for care.

PMID- 8551815
TI  - Monkeying with humankind.

PMID- 8551816
TI  - Redefining the unacceptable.

PMID- 8551817
TI  - A not-so-sensible drinks policy.

PMID- 8551818
TI  - Medical management of unstable angina.

PMID- 8551819
TI  - Genetic testing, common diseases, and health service provision.

PMID- 8551820
TI  - Cholesterol, diastolic blood pressure, and stroke: 13,000 strokes in 450,000
      people in 45 prospective cohorts. Prospective studies collaboration.
AB  - Individual studies of stroke have not clearly answered two questions: on the
      relation, if any, between total blood cholesterol and stroke; and on how the
      strength of the relation between diastolic blood pressure and stroke varies with
      age. The associations of blood cholesterol and diastolic blood pressure with
      subsequent stroke rates were investigated by review of 45 prospective
      observational cohorts involving 450,000 individuals with 5-30 years of follow-up
      (mean 16 years, total 7.3 million person-years of observation), during which
      13,397 participants were recorded as having had a stroke. Most of these were
      fatal strokes in studies that recorded only mortality and not incidence, but
      about one-quarter were from studies that recorded both fatal and non-fatal
      strokes. After standardization for age, there was no association between blood
      cholesterol and stroke except, perhaps, in those under 45 years of age when
      screened. This lack of association was not influenced by adjustment for sex,
      diastolic blood pressure, history of coronary disease, or ethnicity (Asian or non
      Asian). However, because the types of the strokes were not centrally available,
      the lack of any overall relation might conceal a positive association with
      ischaemic stroke together with a negative association with haemorrhagic stroke.
      When the highest and the lowest of the six blood pressure categories were
      compared, the difference in usual diastolic blood pressure was 27 mm Hg (102 vs
      75 mm Hg), and there was a fivefold difference in stroke risk. This fivefold
      difference was seen both in those with a pre-existing history of coronary heart
      disease and in those without it. The proportional difference in stroke risk,
      however, was more extreme in middle than in old age. Among those aged < 45, 45
      64, and 65+ when screened, the differences in the relative risks of stroke
      (between the highest diastolic blood pressure category and a combination of the
      lowest two categories) were tenfold, fivefold, and twofold, respectively.
      However, because the absolute stroke risks are greater in old age, the absolute
      differences in the annual stroke rates showed an opposite pattern, being 2, 5,
      and 8 per thousand, respectively. This suggests that the effects of therapeutic
      blood pressure reductions should be assessed separately in middle age and in old
      age.

PMID- 8551821
TI  - Randomised, double-blind trial of intravenous diltiazem versus glyceryl
      trinitrate for unstable angina pectoris.
AB  - The effect of dihydropyridines in patients with unstable angina is discouraging.
      To find out the effect of the non-dihydropyridine-like calcium-channel blocker
      diltiazem, a randomised, double-blind trial was conducted comparing diltiazem
      with glyceryl trinitrate, both given intravenously, in 129 patients with unstable
      angina. The endpoints were refractory angina or myocardial infarction,
      individually and as a composite endpoint. Refractory angina alone or together
      with myocardial infarction occurred significantly less commonly in the diltiazem
      group. While patients were on the trial drugs the numbers with refractory angina
      were 6 (10%) in the diltiazem group versus 17 (28%) in the glyceryl trinitrate
      group (relative risk 0.36, p = 0.02), and the numbers with refractory angina and
      myocardial infarction were 9 (15%) versus 23 (38%) (relative risk 0.40, p =
      0.007). Over 48 h the number were: refractory angina 8 (13%) versus 18 (30%),
      relative risk 0.45, p = 0.03, and refractory angina and myocardial infarction 12
      (20.0%) versus 25 (41%), relative risk 0.49, p = 0.02. Patients in the diltiazem
      group had better (p < 0.05) event-free survival while taking the drugs. Heart
      rate pressure product was reduced significantly only by diltiazem (p < 0.05). The
      incidence of bradyarrhythmias did not differ significantly. Atrioventricular
      conduction disturbances occurred in 5 (8%) patients in the diltiazem group but
      were not seen in the glyceryl trinitrate group (p = 0.03). These disturbances
      could be reversed by decreasing the dose of the drug or withdrawing it. No
      temporary pacemakers were required. Headache requiring an analgesic or dose
      adjustment occurred significantly less in the diltiazem group: 3 (5%) versus 15
      (25%), relative risk 0.20 (p < 0.004). These results indicate that intravenous
      diltiazem, compared with intravenous glyceryl trinitrate, significantly reduces
      ischaemic events and can be used safely in patients with unstable angina.

PMID- 8551822
TI  - Mortality of cadaveric kidney transplantation versus combined kidney-pancreas
      transplantation in diabetic patients.
AB  - In the United States diabetes in now the principle cause of end-stage renal
      disease. For diabetic patients undergoing cadaveric kidney transplantation, a
      combined kidney-pancreas (KP) transplant is often recommended because this option
      is perceived to carry no additional risk. However, most transplant centres have
      restricted KP transplantation to patients with few diabetic complications and no
      coronary artery disease. We compared survival rates after KP transplantation with
      those after kidney transplantation alone in clinically similar though non
      randomised patient groups. In 173 consecutive diabetic renal transplant
      candidates, 3-year patient survival in 54 KP recipients was 68%, versus 90% in 46
      patients who received a cadaveric kidney alone (p = 0.01). The remaining patients
      had a living-related-donor kidney transplant, either alone (65) or followed 4-20
      months later by a pancreas transplant (8), with survival similar to that with a
      cadaveric kidney. Independent variables associated with early death were age,
      history of congestive heart failure, and pancreas transplantation. A serious
      complication of pancreas transplantation was infection, or which 14 of 54
      recipients required pancreatectomy; KP recipients had a higher death rate from
      infection in the first 12 months (p = 0.034). In view of the excess mortality
      associated with KP transplantation, we suggest that the combined operation should
      be reserved for young patients with no history of congestive heart failure, or
      for patients in whom hyperglycaemia is life-threatening. A randomised trial is
      needed to compare the long-term outcomes of these procedures.

PMID- 8551823
TI  - Breast cancer imaging with radiolabelled peptide from complementarity-determining
      region of antitumour antibody.
AB  - Specific tumour imaging with radiolabelled monoclonal antibodies has been
      extensively investigated. Although some success has been reported, there are many
      limitations due to the slow kinetics, poor extravasation, catabolism by the
      reticuloendothelial system, and non-specific uptake of macromolecules such as
      antibodies. We have tried to overcome some of the problems associated with
      monoclonal antibodies while retaining their specificity by using an antibody
      derived synthetic peptide. A synthetic pentadecapeptide (alpha M2) derived from
      the third heavy-chain complementarity-determining region (CDR-3H) of a tumour
      associated monoclonal antibody was produced and shown to retain its specificity
      against the pan-carcinoma cell-surface antigen, polymorphic epithelial mucin,
      detected by the parent antibody. The peptide was radiolabelled with technetium
      99m and injected intravenously to image malignant lesions in 26 women with
      primary, recurrent, or metastatic breast cancer. Visualisation of breast tumours
      and their metastases was obtained shortly after administration of alpha M2, and
      was optimum by 3 h. Overall, 57 (77%) of 74 sites were visualised. Successful
      imaging was achieved in 14 of 15 primary tumour sites and all of eight local
      recurrences. Five of six metastases in the opposite breast, eight of 15
      metastatic axillary lymph nodes, and all of six metastatic supraclavicular lymph
      nodes were imaged. Metastatic sites in the lungs, mediastinum, chest wall, and
      liver were poorly visualised because of background cardiac blood pool. alpha M2
      detected small lesions ( < 2 cm) as efficiently as larger ones. The peptide was
      rapidly (3 h) cleared from the circulation. No acute or chronic adverse reactions
      due to the alpha M2 were observed. Specific tumour targeting with the
      radiolabelled anticancer peptide alpha M2 offers new opportunities for breast
      cancer imaging and possibly therapy.

PMID- 8551824
TI  - Prospective randomised study of effect of octreotide on rebleeding from
      oesophageal varices after endoscopic ligation.
AB  - Up to a third of patients have early rebleeding from oesophageal varices after
      endoscopic variceal ligation. Octreotide infusion is effective for control of
      variceal bleeding. We investigated the efficacy of octreotide infusion as an
      adjunct to endoscopic variceal ligation to prevent early rebleeding from varices.
      100 consecutive patients admitted with endoscopically confirmed oesophageal
      varices and active bleeding or signs of recent haemorrhage were randomly assigned
      endoscopic variceal ligation alone or octreotide (50 micrograms intravenous bolus
      injection followed by intravenous infusion at 50 micrograms per h for 5 days)
      plus endoscopic variceal ligation. Three patients in each group were excluded.
      Bleeding was controlled in 44 of 47 patients who received variceal ligation alone
      and in 45 of 47 who received combined treatment (p = 1.0). Recurrent bleeding was
      documented in 18 (38% [24-52]) patients who received variceal ligation alone and
      in four (9% [3-21] who received combined treatment (p = 0.0007). The relative
      risk of rebleeding was lower (0.22 [0.08-0.60]) in the combined therapy group.
      Ten patients in the variceal ligation group and one in the combined therapy group
      required balloon tamponade for massive haematesis and haemodynamic instability (p
      = 0.0039). The in-hospital and 30-day mortality rates were higher in the variceal
      ligation group than in the combined therapy group (19 vs 9% and 23 vs 11%), but
      the differences did not reach significance. The relative risks of in-hospital
      (0.5 [0.04=5.3]) and 30-day (0.45 [0.17-1.2]) mortality were lower in the
      combined therapy group. Octreotide significantly reduces recurrent bleeding and
      the need for balloon tamponade in patients with variceal haemorrhage treated by
      endoscopic variceal ligation.

PMID- 8551825
TI  - Transmission of Ebola virus (Zaire strain) to uninfected control monkeys in a
      biocontainment laboratory.
AB  - Secondary transmission of Ebola virus infection in humans is known to be caused
      by direct contact with infected patients or body fluids. We report transmission
      of Ebola virus (Zaire strain) to two of three control rhesus monkeys (Macaca
      mulatta) that did not have direct contact with experimentally inoculated monkeys
      held in the same room. The two control monkeys died from Ebola virus infections
      at 10 and 11 days after the last experimentally inoculated monkey had died. The
      most likely route of infection of the control monkeys was aerosol, oral or
      conjunctival exposure to virus-laden droplets secreted or excreted from the
      experimentally inoculated monkeys. These observations suggest approaches to the
      study of routes of transmission to and among humans.

PMID- 8551826
TI  - Natural history of untreated cytomegalovirus retinitis.
AB  - Cytomegalovirus infection is common in patients with AIDS, and often causes
      retinitis. Treatment is rarely curative, but the progression of retinitis is
      delayed. The untreated course of cytomegalovirus retinitis in AIDS is unknown. We
      report a 35-year-old man with retinitis who refused treatment. Retinitis resulted
      in blindness within 6 months. Measurement of cytomegalovirus genomes showed an
      increasing viral load in blood and urine.

PMID- 8551827
TI  - A 3-month-old girl with fever and respiratory distress.

PMID- 8551828
TI  - Acute bacterial meningitis.

PMID- 8551829
TI  - Media wars.

PMID- 8551830
TI  - Masaccio's cripple: a neurological syndrome. Its art, medicine, and values.

PMID- 8551831
TI  - Now show me your tongue: a taste of medicine in China.

PMID- 8551832
TI  - New tobacco wars reach China.

PMID- 8551833
TI  - Minamata disease redress settled.

PMID- 8551834
TI  - Alcohol-free pastis and hypokalaemia.

PMID- 8551835
TI  - Breast cancer and very-low-dose X-rays.

PMID- 8551836
TI  - HRT and breast cancer.

PMID- 8551837
TI  - Spina bifida, 677T-->C mutation, and role of folate.

PMID- 8551838
TI  - Phaehyphomycosis caused by Veronea bothryosa.

PMID- 8551839
TI  - False-memory syndrome.

PMID- 8551840
TI  - Low vaginal pH and urinary-tract infection.

PMID- 8551841
TI  - False memory syndrome.

PMID- 8551842
TI  - Necrobacillosis: are we missing the early stages of this life-threatening
      infection?

PMID- 8551843
TI  - Nematodes in stools.

PMID- 8551844
TI  - Systolic propulsion of the eyeballs in tricuspid regurgitation.

PMID- 8551845
TI  - Monitoring of cyanocobalamin and hydroxocobalamin during treatment of cyanide
      intoxication.

PMID- 8551846
TI  - Salmon, ventilation, and mycotoxin inhalation.

PMID- 8551847
TI  - Streptococcus suis as threat to pig-farmers and abattoir workers.

PMID- 8551848
TI  - Decriminalisation of cannabis.

PMID- 8551849
TI  - Decriminalisation of cannabis.

PMID- 8551850
TI  - Decriminalisation of cannabis.

PMID- 8551851
TI  - Decriminalisation of cannabis.

PMID- 8551852
TI  - Decriminalisation of cannabis.

PMID- 8551854
TI  - Decriminalisation of cannabis.

PMID- 8551853
TI  - Decriminalisation of cannabis.

PMID- 8551855
TI  - Decriminalisation of cannabis.

PMID- 8551856
TI  - Placebo and EU guidelines.

PMID- 8551857
TI  - Prescribing costs in general practice fundholding.

PMID- 8551859
TI  - Release of Syrian doctors.

PMID- 8551858
TI  - Maternal health and the World Bank.

PMID- 8551860
TI  - Neural networks.

PMID- 8551861
TI  - Neural networks.

PMID- 8551862
TI  - SMN gene deletions in adult-onset spinal muscular atrophy.

PMID- 8551863
TI  - Melanin, melanocytes, and melanoma.

PMID- 8551864
TI  - Influenza types and patient population.

PMID- 8551865
TI  - Breastfeeding as prophylaxis against atopic disease.

PMID- 8551866
TI  - Fatal air embolism resulting from gastroscopy.

PMID- 8551867
TI  - Do serum antibodies to heat-shock protein 65 relate to age or stroke?

PMID- 8551868
TI  - Absence of herpesvirus-like DNA sequences in skin cancers of non-immunosuppressed
      patients.

PMID- 8551869
TI  - Feverish granny syndrome.

PMID- 8551871
TI  - Index volume 346. July-December 1995.

PMID- 8551870
TI  - Gourmet lunches boost staff morale.

PMID- 8551872
TI  - Walking on the moon.

PMID- 8551873
TI  - Reflections on the Seven Countries Study.

PMID- 8551874
TI  - Gestational diabetes and beyond.

PMID- 8551875
TI  - Acellular pertussis vaccines: new vaccines for an old disease.

PMID- 8551876
TI  - Water channels in health and disease.

PMID- 8551877
TI  - Medicines mismatch.

PMID- 8551878
TI  - Detection of virus in vertically exposed HIV-antibody-negative children.
AB  - BACKGROUND: HIV-infected mothers can transmit their infection to their children
      in utero or at delivery (vertical transmission). There have been cases of
      children who were reported as acquiring infection vertically and later clearing
      the infection. We report the frequency of this phenomenon in a European cohort
      study. METHODS: In four centres of the European Collaborative Study of children
      born to HIV-infected mothers, 299 children became HIV-antibody-negative and 264
      of these had been followed up with virus culture and PCR for viral DNA at least
      once. FINDINGS: Nine of the 264 children were positive by virus culture or PCR,
      and subsequently seroreverted. Two of the nine tested virus-positive after they
      became antibody-negative. Six cases were virus-positive early in life and became
      negative thereafter, which is consistent with clearance of infection. The pattern
      was less clear in the other three. The nine cases had had their last virus test
      at age 16-101 months. All nine children had been bottlefed only. Eight had been
      delivered vaginally. The children had no HIV-related symptoms and received no
      anti-HIV treatments. Based on only those children who had two or more positive
      virological tests, we estimate that 2.7% (6/219) cleared or "tolerated" the
      virus. INTERPRETATION: The detection of virus or viral DNA in "uninfected"
      children born to HIV-infected mothers was rare and was not associated with
      clinical disease or immunological abnormalities. The timing of samples will
      affect the documentation of clearance since, in uninfected children of HIV
      positive mothers who cleared the virus, viraemia was intermittent. Current
      paediatric opinion is to inform parents of children who serorevert that the child
      is not HIV-infected.

PMID- 8551879
TI  - Long-term follow-up of patients with Crohn's disease treated with azathioprine or
      6-mercaptopurine.
AB  - BACKGROUND: Crohn's ulcerative gastrointestinal disease is presently managed
      through a variety of medical interventions, including-according to severity of
      illness-anti-inflammatory, immunosuppressive, and corticosteroid agents; and with
      remedial surgery to correct anatomical abnormalities caused by disease processes.
      The immunosuppressant azathioprine (or its metabolite, 6-mercaptopurine) is
      considered an efficient maintenance therapy for Crohn's, but there is always
      concern about bone-marrow suppression, liver damage, and other adverse effects.
      For how long persons with this disease should be given these drugs has not been
      determined. METHODS: Patients who were treated with azathioprine or 6
      mercaptopurine for more than 6 months, and who were in prolonged clinical
      remission (> 6 months without steroids) were followed. The time-to-relapse was
      analysed in those on treatment, in those who stopped treatment for reasons other
      than a relapse, and in the whole sample, taking into account that they could be
      treated with the drugs or not, as a function of time. The influence of
      concomitant variables on time-to-relapse rate was examined using the Cox
      proportional hazard model. FINDINGS: In the 157 patients who continued to take
      the therapy, cumulative probabilities of relapse at 1 and 5 years were 11% and
      32% respectively. Female gender, younger age, and a time for achieving remission
      more than 6 months were associated with a higher risk of relapse. In 42 patients
      who stopped therapy, probabilities of relapse at 1 and 5 years were 38% and 75%,
      respectively. Male gender, younger age and duration of remission less than 4
      years were associated with a higher risk of relapse. After 4 years of remission
      on these drugs, the risk of relapse appeared to be similar, whether the therapy
      was maintained or stopped. INTERPRETATION: Taking into account the potential
      risks of long-term immunosuppressive therapy, the usefulness of maintaining
      azathioprine or 6-mercaptopurine in patients who have been in remission for more
      than 4 years is questionable.

PMID- 8551880
TI  - Chronic granulomatous disease in adults.
AB  - BACKGROUND: Chronic granulomatous disease (CGD), an inherited disorder of
      granulocyte function caused by failure of intracellular superoxide production,
      normally presents in the first years of life with severe recurrent bacterial and
      fungal infections. METHODS: From the files of two children's hospitals we
      identified 11 CGD patients who were remarkable for an unusually late diagnosis,
      at 13-43 years of age. Their clinical and laboratory features were examined.
      FINDINGS: The first clinical manifestation occurred at a median age of 3.6 years
      but CGD was not diagnosed until a median age of 22 years. Pneumonias and
      abscesses caused by Staphylococcus aureus and Aspergillus species were the most
      frequent infections. Granulomas, often leading to chronic complications, occurred
      in 7 of the patients. With 1.1 severe infections in 100 patient months, the 11
      patients had a lower frequency of severe infections than patients with classic
      CGD; however, such infections could be equally life-threatening. 8 of the
      patients had X-linked CGD with small but detectable quantities of cytochrome
      b558, normally absent in X-linked CGD; and 3 had autosomal-recessive CGD. 9
      patients had residual production of reactive oxygen metabolites, a feature that
      could explain the low incidence of infections. INTERPRETATION: CGD in adults may
      be more common than previously assumed. In view of the possibility of timely
      treatment, infection prophylaxis, and genetic counselling for affected families,
      CGD should be excluded in any patient with unexplained infections or granulomas.

PMID- 8551881
TI  - Clinical algorithm for treatment of Plasmodium falciparum malaria in children.
AB  - BACKGROUND: Identification of children who need antimalarial treatment is
      difficult in settings where confirmatory laboratory testing is not available, as
      in much of sub-Saharan Africa. The current national policy in Malawi is to treat
      all children with fever, usually defined as the mother's report of fever in the
      child, for presumed malaria. To assess this policy and to find out whether a
      better clinical case definition could be devised, we studied acutely ill children
      presenting to two hospital outpatient departments in Malawi. METHODS: The parent
      or guardian of each enrolled child (n = 1124) was asked a standard series of
      questions about the symptoms and duration of the child's illness. Each child was
      examined, axillary and rectal temperatures and blood haemoglobin concentrations
      were measured, and a giemsastained thick smear was examined for malaria
      parasites. Logistic regression procedures were used to identify clinical
      predictors of parasitaemia. FINDINGS: High temperature (37.7 degrees C or above),
      nailbed pallor, enlarged spleen, and being seen at one of the clinics rather than
      the other were associated with an increased risk of malaria parasitaemia in
      univariate analyses. A revised malaria case definition of rectal temperature of
      37.7 degrees C or higher, splenomegaly, or nailbed pallor was 85% sensitive in
      identifying parasitaemic children and 41% specific; the corresponding sensitivity
      and specificity for the nationally recommended definition that equates mother's
      history of fever with malaria were 93% and 21%. The revised case definition had
      89% sensitivity in identifying parasitaemic children with haemoglobin
      concentration below 80 g/L and 89% sensitivity in identifying children with
      parasite density greater than 10,000/microL, characteristics that indicate a
      clear need for antimalarial treatment. INTERPRETATION: These results suggest that
      better clinical definitions are feasible, that splenomegaly and pallor are
      helpful in identifying children with malaria, and that much overtreatment of
      children without parasitaemia could be avoided.

PMID- 8551882
TI  - Long-term diabetogenic effect of single pregnancy in women with previous
      gestational diabetes mellitus.
AB  - BACKGROUND: Pregnancy is associated with marked insulin resistance that seems to
      have little, if any, impact on the long-term risk of non-insulin-dependent
      diabetes mellitus (NIDDM) in the general population. The aim of this study was to
      test whether pregnancy would alter the risk of NIDDM among women with a high
      prevalence of pancreatic beta-cell dysfunction, as indicated by a history of
      gestational diabetes mellitus. METHODS: The cohort consisted of 666 Latino women
      with gestational diabetes attending a high-risk family planning clinic. They were
      followed up for up to 7.5 years, during which time they were weighed and
      underwent an oral glucose-tolerance test annually. The effect of an additional
      pregnancy, and of other risk factors for diabetes, was examined. FINDINGS: 87
      (13%) of the women completed an additional pregnancy. 80 of those women did not
      have NIDDM immediately after the additional pregnancy and their subsequent annual
      incidence rate of NIDDM was 30.9% (95% CI 12.7-49.1), more than 2.5 times the
      annual incidence rate of NIDDM in the cohort overall (11.9%; 95% CI 10.0-13.8).
      Proportional hazards regression analysis using the presence or absence of an
      additional pregnancy as a time-dependent variable confirmed that an additional
      pregnancy increased the rate ratio of NIDDM to 3.34 (95% CI 1.80-6.19), compared
      with women without an additional pregnancy after adjustment for other potential
      diabetes risk factors during the index pregnancy (antepartum oral glucose
      tolerance, highest fasting glucose, gestational age at diagnosis of gestational
      diabetes) and during follow-up (postpartum body mass index [BMI], and glucose
      tolerance, weight change, breast feeding, and months of contraceptive use).
      Weight gain also was independently associated with an increased risk of NIDDM;
      the rate ratio was 1.95 (95% CI 1.63-2.33) for each 10 lb (4.5 kg) gained during
      follow-up after adjustment for the additional pregnancy and the other potential
      risk factors. INTERPRETATION: The study showed that a single pregnancy,
      independent of the well-known effect of weight gain, accelerated the development
      of NIDDM in a group of women with a high prevalence of pancreatic beta-cell
      dysfunction. This finding implies that episodes of insulin resistance may
      contribute to the decline in beta-cell function that leads to NIDDM in many high
      risk individuals.

PMID- 8551883
TI  - Preliminary description of focal segmental glomerulosclerosis in patients with
      renovascular disease.
AB  - BACKGROUND: Primary and secondary forms of focal segmental glomerulosclerosis
      (FSGS) are common causes of glomerular proteinuria. Secondary forms of FSGS seem
      to be the result of adaptive changes that follow a reduction in renal mass. We
      saw an elderly patient with severe bilateral renal vascular disease (RVD) who had
      FSGS on percutaneous biopsy. To find out whether elderly patients with
      atherosclerotic RVD are predisposed to the development of FSGS, we reviewed all
      cases of FSGS at our institution between 1990 and 1995. METHODS: We identified 59
      cases of biopsy-proven FSGS and examined clinical, histological, and radiographic
      records. FINDINGS: Of the 59 patients, 24 were older than 50 years; eight of
      these had RVD. No patient under the age of 50 had RVD. Seven of the eight
      patients with RVD and FSGS had substantial proteinuria at presentation. All had
      typical glomerular lesions with focal segmental tuft collapse and synechiae;
      other glomeruli were hypertrophic. All patients showed further decline in renal
      function on follow-up. INTERPRETATION: The association of FSGS and RVD may
      represent an under-recognised aetiology of significant proteinuria in elderly
      patients.

PMID- 8551884
TI  - Comparison of 99mTc infecton imaging with radiolabelled white-cell imaging in the
      evaluation of bacterial infection.
AB  - BACKGROUND: Bacterial infection can pose a substantial diagnostic dilemma.
      Techniques involving radiolabelled leucocytes can pinpoint the site of
      inflammation. However, previous radiolabelling techniques have failed to
      distinguish between bacterial-mediated infection and non-bacterial inflammation.
      To overcome this difficulty, we have studied a radiopharmaceutical, technetium
      99m (99mTc) Infecton, which is based on the antibiotic ciprofloxacin. METHODS: We
      used this agent to image bacterial infection in 56 patients (one twice) with
      known or suspected sites of infection. We then compared the imaging results of
      these patients with those from a radiolabelled leucocyte study. FINDINGS: The
      concordance rate was 68% (39 out of 57 images). In 18 discordant results 99mTc
      Infecton was correctly positive in 8 out of 9 positive studies and correctly
      negative in 4 out of 9 negative studies. 4 out of 5 of the falsely negative
      studies were in patients who had taken antibiotics for over 7 days. We found that
      99mTc Infecton gave better imaging results than radiolabelled leucocytes.
      Comparison between 99mTc Infecton and leucocyte imaging gave sensitivities of 84%
      and 81%, and specificities of 96% and 77%, respectively. INTERPRETATION: We
      believe that the specificity 99mTc Infecton confers for bacterial infection and
      its ease of administration are the main advantages of this new agent.

PMID- 8551885
TI  - Dementia in a 58-year-old woman.

PMID- 8551886
TI  - Myths about the treatment of addiction.

PMID- 8551887
TI  - How to deal with regression to the mean in intervention studies.

PMID- 8551888
TI  - Medical evacuation from Mostar.

PMID- 8551889
TI  - Beta-carotene takes a collective beating.

PMID- 8551890
TI  - Preparing for battle against vancomycin resistance.

PMID- 8551891
TI  - Safety of modern oral contraceptives.

PMID- 8551892
TI  - Safety of modern oral contraceptives.

PMID- 8551893
TI  - Safety of modern oral contraceptives. The International Committee for Research in
      Reproduction.

PMID- 8551894
TI  - Safety of modern oral contraceptives.

PMID- 8551895
TI  - Safety of modern oral contraceptives.

PMID- 8551896
TI  - Safety of modern oral contraceptives.

PMID- 8551897
TI  - Activated protein C resistance in childhood stroke.

PMID- 8551898
TI  - Does surgery disseminate or accelerate cancer?

PMID- 8551899
TI  - Safety of modern oral contraceptives.

PMID- 8551900
TI  - Abnormal lipid profiles on fibrate derivatives.

PMID- 8551901
TI  - Sickle cell pain crisis.

PMID- 8551902
TI  - Treatment of hypertrophic cardiomyopathy.

PMID- 8551903
TI  - Sickle cell pain crisis.

PMID- 8551904
TI  - Sickle cell pain crisis.

PMID- 8551905
TI  - Sickle cell pain crisis.

PMID- 8551906
TI  - Crohn's disease, measles, and measles vaccination: a case-control failure.

PMID- 8551907
TI  - Sickle cell pain crisis.

PMID- 8551908
TI  - Left anterior small thoracotomy (LAST) for coronary artery revascularisation.

PMID- 8551909
TI  - Dopamine receptors in schizophrenia.

PMID- 8551910
TI  - HIV co-infection with a currently non-pathogenic flagellate.

PMID- 8551911
TI  - Pseudomonas aeruginosa exotoxin A antibodies in rapidly deteriorating chronic leg
      ulcers.

PMID- 8551912
TI  - Case reports.

PMID- 8551913
TI  - Costing of antiepileptic drugs.

PMID- 8551914
TI  - Inquiring into sex.

PMID- 8551915
TI  - Influence of necropsy on clinical practice.

PMID- 8551916
TI  - Little arrows.

PMID- 8551917
TI  - Coeliac disease and follicular gastritis.

PMID- 8551918
TI  - Prevention of cytomegalovirus disease in transplant recipients.

PMID- 8551919
TI  - IgG ELISA antibodies and detection of Helicobacter pylori in elderly patients.

PMID- 8551920
TI  - IgG ELISA antibodies and detection of Helicobacter pylori in elderly patients.
      Italian Helicobacter pylori Study Group.

PMID- 8551921
TI  - Serum gastrin and secretin test in Zollinger-Ellison syndrome.

PMID- 8551922
TI  - Snoring--a common cause of voiding disturbance in elderly men.

PMID- 8551923
TI  - Angioplasty versus bypass surgery.

PMID- 8551924
TI  - Angioplasty versus bypass surgery.

PMID- 8551925
TI  - Glycosylated haemoglobin and transient erythroblastopenia of childhood.

PMID- 8551926
TI  - Undefined high-power fields.

PMID- 8551927
TI  - "Are you playing evidence-based medicine games with our daughter?".

PMID- 8551928
TI  - Too many haematologists on one aeroplane.

PMID- 8551929
TI  - Infant feeding: preventing the pitfalls.

PMID- 8551930
TI  - The need for security with computerized records.

PMID- 8551931
TI  - Therapeutic implications of recent advances in cystic fibrosis.

PMID- 8551932
TI  - A structured intervention improves breastfeeding success for ill or preterm
      infants.

PMID- 8551933
TI  - When women decide not to breastfeed.

PMID- 8551934
TI  - A developmental approach to weaning.

PMID- 8551935
TI  - Grandparents as primary caregivers.

PMID- 8551936
TI  - How can a nurse care for me?

PMID- 8551937
TI  - Solve the puzzle of pediatric cardiopulmonary failure.

PMID- 8551938
TI  - Maintaining an ethical stand without jeopardizing your job.

PMID- 8551939
TI  - Using the telephone in patient and family teaching.

PMID- 8551940
TI  - Prenatal and postnatal: use of corticosteroids.

PMID- 8551941
TI  - Adhesins of Escherichia coli associated with extra-intestinal pathogenicity
      confer binding to colonic epithelial cells.
AB  - Escherichia coli adhesins are virulence factors in intestinal and extra
      intestinal infections, but their role in normal intestinal colonization has not
      been defined. We investigated the intestinal adherence of E. coli with Dr
      hemagglutinin, S fimbriae, CFA/I or CFA/II, using freshly isolated ileal or
      colonic enterocytes and cells from the human colonic cell line HT-29. E. coli
      with S-fimbrial adhesins (Sfa I or Sfa II), P or type 1 fimbriae, adhered in a
      non-polarized manner, and in similar numbers to colonic and ileal enterocytes. S
      fimbriae of the variety Sfa II (originating from a meningitis isolate), mediated
      a stronger binding than Sfa I (of uropathogenic origin). Strains expressing Dr
      hemagglutinin adhered preferentially to the brush borders, slightly better to
      colonic than ileal enterocytes. Strains expressing CFA/I or II adhered to colonic
      and ileal enterocytes, although brush border adherence was predominantly observed
      with ileal cells. Binding to HT-29 cells paralleled binding to colonic
      enterocytes for all adhesin specificities except CFA/I. The results suggest that
      Dr hemagglutinin, P-, type 1- and S-fimbrial adhesins mediate binding to both
      colonic and ileal enterocytes. These specificities may contribute to the
      establishment of E. coli in the intestinal microflora, which precedes their
      spread to extra-intestinal sites.

PMID- 8551942
TI  - Plasmid coding for drug resistance and invasion of epithelial cells in
      enteropathogenic Escherichia coli 0111:H.
AB  - Enteropathogenic Escherichia coli (EPEC) can adhere to, invade and multiply in
      human epithelial cells. To define the elements required for bacterial invasion,
      we isolated from an 0111:H- EPEC a 6.6 kb plasmid that is capable of conferring
      to an avirulent, non-adherent E. coli K12 strain (DK1) the capacity to invade
      epithelial cells. With this system a dissociation was possible between bacterial
      invasion and adherence to epithelial cells. Bacteria containing this plasmid
      synthesise a protein of 32 kDa (pl 4.93) which seemed to be required for cell
      invasion. The results provide a new basis for strategies to prevent EPEC
      infections.

PMID- 8551943
TI  - Phase-shift of polysaccharide capsule expression in group B streptococci, type
      III.
AB  - The type-specific polysaccharide capsule is an important virulence determinant in
      group B streptococci (GBS). The previously described inverse relationship between
      the buoyant density of a GBS-isolate and the capsular thickness was used to
      assess the frequencies of polysaccharide capsular phase-shift in clinical GBS,
      type III strains. Shift from intermediate density (ID) of parental strains, to
      high density (HD), i.e. shift from intermediate capsule thickness to poor
      encapsulation, was found to range from 1.2 x 10(-3) to 4.8 x 10(-6). Shift from
      ID to low density (LD), i.e. shift to abundant encapsulation, ranged from 1.9 x
      10(-4) to 1.1 x 10(-7). Shifts were reversible in all cases, either directly (HD-
      >LD or vice versa) or through intermediate forms. Reversion frequencies were in
      some isolates as high as 10(-1). Phase-shift frequencies differed more than a
      thousand-fold between compared strains. Differences in phenotypic shift between
      strains were validated using flow cytometry. Possible modulation of capsule
      expression by changes in culture conditions was assessed. Variation of
      temperature, oxygen-tension, and presence of human serum did not affect capsule
      expression. However, growth at pH below 5.5 decreased the amount of capsule bound
      native type III polysaccharide, probably through phenotypic modification rather
      than genetic shift. IS861, an insertion sequence which has been proposed a
      regulatory function on the GBS capsule expression, was found in multiple copies
      in the isolates investigated. No differences in copy number or location of IS861
      between the differently encapsulated phenotypes were found.

PMID- 8551944
TI  - Vaccination of mice with attenuated mutants of Listeria monocytogenes:
      requirement for induction of macrophage la expression.
AB  - Isogenic mutant strains of Listeria monocytogenes demonstrating graded
      attenuation in mice were used to analyse the correlation between bacterial
      virulence, ability to induce class II MHC (la) molecules in antigen presenting
      cells and ability to vaccinate against secondary infection. The mutants used
      differed only in the amino acid sequence of the thiol-activated hemolysin,
      Listeriolysin O (LLO). The results indicate that L. monocytogenes mutants of
      reduced virulence have the potential to act as vaccines only if they are
      sufficiently persistent to induce la expression in antigen presenting cells. The
      findings also suggest that specific mutagenesis of virulence factors, including
      LLO, could provide an approach for creating Listeria monocytogenes strains with
      potential for use as attenuated live vaccines.

PMID- 8551945
TI  - The Neisseria meningitidis outer membrane protein P1 produced in Bacillus
      subtilis and reconstituted into phospholipid vesicles elicits antibodies to
      native P1 epitopes.
AB  - Class 1 outer membrane protein (P1) of Neisseria meningitidis group B is
      considered a promising vaccine candidate because P1 subtype-specific antibodies
      have been shown to be protective in an animal model. We have previously described
      the production of P1 in the Gram-positive Bacillus subtilis as intracellular
      inclusion bodies, from which the protein (BacP1) is easily purified (Nurminen et
      al., Mol. Microbiol., 1992, 2499-2506). We show here that the purified BacP1 can
      be reconstituted into phospholipid vesicles with the formation of the native
      immunodominant surface epitopes. The detergent-solubilized, completely denatured
      BacP1 was fused with phospholipid-detergent micelles during detergent removal by
      dialysis or gel filtration to yield protein-lipid vesicles (liposomes). When mice
      were immunized with these liposomes, they produced high titers of antibodies
      reacting in a P1 subtype-specific manner with meningococcal cells indicating the
      presence of conformation-dependent P1-specific epitopes in the liposomes. The
      results suggest that a vaccine candidate for meningococcal disease could be
      developed from the BacP1-liposomes. They furthermore demonstrate the feasibility
      of refolding a denatured outer membrane protein, which has never been exposed to
      lipopolysaccharide, into a native-like conformation.

PMID- 8551947
TI  - Inter-relation of sylvatic and domestic transmission of Trypanosoma cruzi in
      areas with and without domestic vectorial transmission in Minas Gerais, Brazil.
AB  - During the period 1980-1986, we captured triatomine bugs and mammalian reservoir
      hosts from sylvatic and domestic situations in different municipalities of the
      State of Minas Gerais. Trypanosoma cruzi was isolated from captured bugs, mammals
      and patients. After cultivation in LIT medium, the electrophoretic enzyme
      profiles were determined. We obtained a total of 32 parasite isolates from
      regions with active domestic transmission, and 24 isolates from areas under
      control. For the first areas the results suggest introduction of T. cruzi from
      sylvatic habitats, through incursion of infected opossums and/or sylvatic T.
      sordida, which appears to have given rise to at least one acute human infection.
      Of particular interest is the finding of sylvatic opossums and a T. sordida nymph
      infected with ZB, that could indicate return of parasites from chronic human
      infections to sylvatic transmission cycles. For the areas under control we also
      interpret the results as interaction between sylvatic and domestic cycles of
      transmission, here through the invasion of houses by bugs carrying the Z1
      zymodeme from the sylvatic environment. The Multivariate Correspondence Analysis
      gives a spatial description between the different parasite isolates and confirms
      the existence of a bridge in the opposite direction in the region with active
      vectorial transmission including the exporting of Z2 through the peridomestic
      environment into the sylvatic cycle. For the other areas this bridge corresponds
      especially to Panstrongylus megistus, importing Z1 into the domestic environment.

PMID- 8551946
TI  - A possible correlation between the host genetic background in the epidemiology of
      hepatitis B virus in the Amazon region of Brazil.
AB  - The Amazon region of Brazil is an area of great interest because of the large
      distribution of hepatitis B virus in specific Western areas. Seven urban
      communities and 24 Indian groups were visited in a total of 4,244 persons. Each
      individual was interviewed in order to obtain demographic and familial
      information. Whole blood was collected for serology and genetic determinations.
      Eleven genetic markers and three HBV markers were tested. Among the most relevant
      results it was possible to show that (i) there was a large variation of previous
      exposure to HBV in both urban and non-urban groups ranging from 0 to 59.2%; (ii)
      there was a different pattern of epidemiological distribution of HBV that was
      present even among a same linguistic Indian group, with mixed patterns of
      correlation between HBsAg and anti-HBs and (iii) the prevalence of HBV markers
      (HBsAg and anti-HBs) were significantly higher (P = 0.0001) among the Indian
      population (18.8%) than the urban groups (12.5%). It is possible that the host
      genetic background could influence and modulate the replication of the virus in
      order to generate HB carrier state.

PMID- 8551948
TI  - Presence of Aeromonas trota in aquatic environment.

PMID- 8551949
TI  - Schistosomiasis in a low prevalence area: incomplete urbanization increasing risk
      of infection in Paracambi, RJ, Brazil.
AB  - The risk of schistosomiasis infection and heavy infection in the locality of
      Sabugo was evaluated in relation to housing in areas with different urbanization
      development and to residential supply with snail-infested water. Critical
      sanitary conditions were found in areas of incomplete urbanization, where healthy
      water supply sources were scarce, and draining of sewage, without previous
      treatment, was made directly to the water-bodies used for domestic and leisure
      activities, despite being Biomphalaria tenagophila snail breeding-places. Stool
      examinations (Kato-Katz and Lutz methods) showed prevalence of 2.9% mean
      intensity of 79 eggs per gram of stool and 47% of positive cases presenting
      intense infection. The use of snail-contaminated water for domestic purposes was
      considered a risk factor for infection. It is concluded that incomplete
      urbanization would facilitate transmission, probably enhancing the intensity of
      infection and that a low prevalence could hide a highly focal transmission. The
      relevance of these facts upon the efficiency of epidemiologic study methods and
      disease control planning are then discussed.

PMID- 8551950
TI  - Longitudinal study of circadian rhythms in the cercarial emergence of Schistosoma
      mansoni from Biomphalaria glabrata.

PMID- 8551951
TI  - Antibody isotypes, including IgG subclasses, in Ecuadorian patients with
      pulmonary paragonimiasis.
AB  - An ELISA test was developed to detect Paragonimus-specific antibodies, including
      IgG subclasses, using P. mexicanus crude water-soluble antigens. The test was
      standardized to detect antibodies in sera of Ecuadorian patients with pulmonary
      paragonimiasis and negative controls from the endemic area. The detected mean
      levels of IgG (0.753, SEM: 0.074) and IgM (0.303, SEM: 0.033) were significantly
      elevated (P < 0.05). Within the IgG subclasses, IgG4 showed the highest detected
      mean level (0.365, SEM: 0.116) and the other three subclasses showed considerably
      lower mean levels (IgG1, 0.186 SEM: 0.06; IgG2, 0.046 SEM: 0.01; IgG3, 0.123 SEM:
      0.047). The number of P. mexicanus eggs found in sputum of infected individuals
      showed a positive correlation with the level of antibodies detected for IgM, IgG
      and its subclasses (P < 0.001). The relevance of these findings in Ecuadorian
      patients suffering from pulmonary paragonimiasis is discussed.

PMID- 8551952
TI  - Characterization of T cell clones from chagasic patients: predominance of CD8
      surface phenotype in clones from patients with pathology.
AB  - Human Chagas' disease, caused by the protozoan Trypanosoma cruzi, is associated
      with pathological processes whose mechanisms are not known. To address this
      question, T cell lines were developed from chronic chagasic patients peripheral
      blood mononuclear cells (PBMC) and cloned. These T cell clones (TCC) were
      analyzed phenotypically with monoclonal antibodies by the use of a fluorescence
      microscope. The surface phenotype of the TCC from the asymptomatic patient were
      predominantly CD4 positive (86%). On the contrary, the surface phenotype CD8 was
      predominant in the TCC from the patients suffering from cardiomegaly with right
      bundle branch block (83%), bradycardia with megacolon (75%) and bradycardia
      (75%). Future studies will be developed in order to identify the antigens
      eliciting these T cell subpopulations.

PMID- 8551953
TI  - Schistosoma mansoni: reinfections and concomitant immunity in mice. Importance of
      perfusion time after challenge infection for evaluation of immunoprotection.
AB  - The concomitant immunity in the presence of repeated infections (with 15
      cercariae) was studied in mice sacrificed on the 20th day after each infection.
      The comparison of the averages of immature worms, recovered from mice submitted
      to reinfection, with those of their respective controls (previously uninfected)
      showed a significantly lower worm recovery rate in the animals with previous
      infections (concomitant immunity). However, statistically significant differences
      could not be detected among the various groups of animals, when the mice that
      accumulated worms in this mature stage were perfused. The theoretical projection
      based on the accumulation of young worms which developed to adult ones indicates
      a lower recovery rate of adult worms in the animals with concomitant immunity,
      but this projection was not corroborated by the experimental data. The visceral
      hemodynamic alterations that occurred in reinfections due to the pathogeny,
      favouring recirculation of the recent arriving worms to the portal system, could
      explain the lower recovery rate of immature worms, which could remain in other
      organs on the occasion of perfusion of the portal system. These results suggest
      that special care should be taken when one wants to investigate concomitant
      immunity in mice based on the distinction of the immature worms from challenge
      infection and the mature ones from primary infection.

PMID- 8551954
TI  - Prevalence of antibodies to potential malaria vaccine antigens in an endemic area
      of the State of Rondonia (Brazil).

PMID- 8551955
TI  - Detection of anti-Schistosoma antibodies in oral fluids.

PMID- 8551956
TI  - Hemagglutinating and fusogenic activities of Newcastle disease virus: studies on
      receptor binding specificity and pH-induced conformational changes.
AB  - Vaccinal and wild strains of Newcastle Disease virus (NDV) were analyzed for cell
      receptor binding and fusogenic biological properties associated with their HN
      (hemagglutinin-neuraminidase) and F (fusion protein) surface structures
      respectively. The evaluation of the biological activities of HN and F was carried
      out respectively by determination of hemagglutinating titers and hemolysis
      percentages, using erythrocytes from various animal origins at different pH
      values. Significant differences in hemagglutination titers for some strains of
      NDV were detected, when interacting with goose, sheep, guinea-pig and human "O"
      group erythrocytes at neutral pH. Diversity of hemolysis percentages was observed
      between different NDV strains at acid pH. These analysis were developed to
      evaluate particular aspects of the actual influence of the receptor specificity
      and pH on the receptor binding and fusogenic processes of Newcastle Disease
      viruses.

PMID- 8551957
TI  - Parasitism of adipocytes by Trypanosoma cruzi.

PMID- 8551958
TI  - Absence of antibody-dependent enhancement (ADE) of viral infectivity in the
      epidemic neuropathy in Cuba.

PMID- 8551959
TI  - A randomized trial of amphotericin B alone or in combination with itraconazole in
      the treatment of mucocutaneous leishmaniasis.
AB  - A randomized trial of amphotericin B (AB) alone and in combination with oral
      itraconazole (IZ) is carried out in two groups of 10 mucocutaneous leishmaniasis
      patients from Bolivia and Peru. AB+IZ combination is no better than AB
      monotherapy, as far as efficacy and tolerability are concerned. No antagonism was
      detected.

PMID- 8551960
TI  - Penicillin tolerance among beta-hemolytic streptococci and production of the
      group carbohydrates, hemolysins, hyaluronidases and deoxyribonucleases.
AB  - Penicillin tolerance among 67 strains of beta-hemolytic streptococci was examined
      by determining the ratio of the minimal bactericidal concentration to the minimal
      inhibitory concentration as 32 or greater. Tolerance was demonstrated in 15 group
      A strains and in 11.7, and 4 of groups B, C and G, respectively. Thereafter the
      effects of a subminimal inhibitory concentration (1/2 MIC) of penicillin on the
      bacterial products of four tolerant and four nontolerant strains (two of each
      Lancefield group) were analyzed and compared. The antibiotic caused a marked
      increase in the expression of the group carbohydrates for strains of group B.
      Penicillin was found to reduce the cell-bound hemolysin activities of the four
      tolerant strains and to increase the activity of the other (free) form of
      nontolerant groups A, C and G hemolysins. Penicillin caused an increase in the
      extracellular hyaluronidase activities of one group A and groups B, C and G
      streptococci. With added antibiotic the production of deoxyribonuclease by
      tolerant groups A, C and G was greatly enhanced and that of the group B
      streptococcus was arrested.

PMID- 8551961
TI  - Repeated focal mollusciciding for snail control in a sugar-cane area of northeast
      Brazil.

PMID- 8551962
TI  - Meetings on vaccine studies towards the control of leishmaniasis. UNDP/World
      Bank/WHO Special Program for Research and Training in Tropical Diseases (TDR)
      February 13-22 and April 4-5, 1995.

PMID- 8551963
TI  - Capitation contracts: why take the risk?
AB  - There is no such thing as a simple acceptance of a capitation contract. There are
      at least four crucial considerations a physician should make before entering into
      such a contract. This article reviews those considerations and other pertinent
      issues.

PMID- 8551964
TI  - Establishing a group practice: here are some reasons why you should consider it.

PMID- 8551965
TI  - The evolution of the Michigan AIDS Fund.

PMID- 8551966
TI  - Immunizing Michigan's children: what went wrong and what can be done to improve
      Michigan's pitiful record?
AB  - "New National Survey: MICHIGAN HAS LOWEST IMMUNIZATION RATE OF ALL 50 STATES FOR
      1994." This headline, which appeared in bold letters, was the lead story in the
      August 25, 1995 edition of The New York Times. In the days following, news media
      around the state highlighted results of the federal Centers for Disease Control
      report that found only 61 percent of Michigan two-year-olds fully immunized,
      while nationally 75 percent of children ages 19-35 months have shots up-to-date.
      In Detroit, the lowest ranked city in the nation, numbers were worse, with just
      half fully immunized by age two. The Ann Arbor News called Michigan's record
      "pitiful," stating, "Our children are too valuable for Michigan to rank last in
      immunization." The Detroit Free Press called the CDC results "a source of shame."
      Noting substantial increases in Michigan's vaccination rate the past four years,
      editorial writers added, "But last is still last."

PMID- 8551967
TI  - Optimum culture conditions for production of exfoliative toxin by Staphylococcus
      hyicus.
AB  - Optimum culture conditions for the production of exfoliative toxin by
      Staphylococcus hyicus (shET) were examined. High shET activity was obtained from
      the culture filtrate of HI and TY broth inoculated with S. hyicus. The pH in
      these two media ranged from 7 to 8.5 during bacterial culture, while the lowest
      pH in TS and BHI broth was less than 6. shET activity in the culture filtrate
      from TY broth inoculated with 10(7) CFU of S. hyicus per ml was higher than that
      in TY broth inoculated with 10(6) and 10(8) CFU of bacteria per ml. When shET
      activity in the culture filtrate was measured under various shaking conditions,
      the culture filtrate shaken at 75 oscillations per min had the highest shET
      activity of the five shaking conditions. shET activity of the culture filtrate of
      TY broth to which protease inhibitor had been added was the same as that of TY
      broth without inhibitor. shET activity in a shaking culture in an Erlenmeyer
      flask was also the same as that in sac culture and that in shaking culture using
      a shaking (Sakaguchi) flask. shET activity in TY broth supplemented with 100 mM
      glucose was significantly lower than that in TY broth without glucose. Based on
      the above results, the optimum culture conditions for the production of shET were
      as follows: inoculation of 3 x 10(9) CFU of S. hyicus strain P-1 into 300 ml of
      TY broth in a 2,000-ml Erlenmeyer flask, and incubation at 37 C with shaking at
      75 oscillations per min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8551968
TI  - Rapid identification by polymerase chain reaction of staphylococcal exfoliative
      toxin serotype A and B genes.
AB  - A new system was designed to detect staphylococcal exfoliative toxin A (ETA) and
      B (ETB) genes by the polymerase chain reaction (PCR). The primer pairs for the
      ETA gene (eta) were 20 and 20-mer, and its PCR product was a 741-bp eta fragment,
      while the primer pairs for the ETB gene (etb) were also 20 and 20-mer, and its
      PCR product was a 629-bp etb fragment. When these primers were simultaneously
      used in the PCR, the two types of ET were clearly detected as two bands in an ETA
      and ETB double-producer using only one colony within 3 hr. We examined 66 strains
      of Staphylococcus aureus isolated from patients with staphylococcal scalded skin
      syndrome (SSSS) and compared the results obtained by ELISA and PCR. The same
      results were obtained for 56 of the strains, i.e., 30 strains were ETA producers,
      20 strains were ETB producers, and 6 strains were double-producers. However,
      positive results were obtained for 5 of the 10 non-ET-producing strains. Two of
      these strains were judged by PCR as ETA producers and three as ETB producers.
      Thus, PCR is very sensitive and rapid in detecting ETA and ETB gene fragments in
      colonies isolated from patients with SSSS.

PMID- 8551969
TI  - Characterization of the dextranase gene (dex) of Streptococcus mutans and its
      recombinant product in an Escherichia coli host.
AB  - The gene (dex), which encodes the Streptococcus mutans dextranase (Dex), was
      cloned in Escherichia coli. The E. coli host harboring a recombinant plasmid
      (pSD2) containing an 8-kb BamHI insert produced a Dex protein of 133 kDa as well
      as smaller enzymes of 118, 104, and 88 kDa. The Dex produced by the recombinant
      E. coli was apparently located in the cytoplasmic fraction, not in the
      periplasmic nor the extracellular fractions. Subcloning and deletion analysis of
      pSD2 showed that the structural gene of Dex was encoded by a 4-kb BamHI-SalI
      fragment. The fragment also contained the dex promoter which was effective in the
      E. coli cell.

PMID- 8551970
TI  - Metastasis-promoting activity of a novel molecule, Ag 243-5, derived from
      mycoplasma, and the complete nucleotide sequence.
AB  - We found that mycoplasma-infected cells have a higher ability to metastasize in
      vivo than non-mycoplasma-infected cells. To investigate this phenomenon, we
      obtained a monoclonal antibody, MAb 243-5, by immunization with Mycoplasma
      arginini-infected RPMI 4788 cells. This MAb recognized a mycoplasmal protein with
      an MW of 47 kDa and completely inhibited the experimental metastasis of M.
      arginini-infected RPMI 4788 cells using a nude mouse model. Using this MAb, we
      purified a molecule called Ag 243-5 and determined the N-terminal amino acid
      sequence and clarified the entire nucleotide sequence of the Ag 243-5 gene. PCR
      analysis showed the existence of a homologous gene in Mycoplasma hyorhinis. Four
      sequential injections of Ag 243-5 (30 micrograms/shot) promoted the experimental
      metastasis of non-mycoplasma-infected RPMI 4788 cells more than 10-fold using a
      nude mouse model. Ag 243-5 also promoted the experimental metastasis of the non
      mycoplasma-infected mouse colon cancer cell line colon 26. This metastasis
      promoting effect was neutralized by MAb 243-5.

PMID- 8551971
TI  - Distribution of virulence factors in Escherichia coli isolated from urine of
      cystitis patients.
AB  - The distribution of 7 urovirulence factors, such as type 1 pilus (pil), pilus
      associated with pyelonephritis (pap), S fimbriae (sfa), afimbrial adhesin I
      (afaI), hemolysin (hly), aerobactin (aer) and cytotoxic necrotizing factor 1
      (cnf1) was examined by a DNA colony hybridization test among 194 Escherichia coli
      strains isolated from the urine of cystitis patients and in 80 strains isolated
      from the stool specimens of healthy adults. All virulence factors examined,
      except pil, were significantly more frequently detected among the cystitis
      isolates than among the fecal isolates. When individual virulence factors were
      analyzed against the others, an association was discernible which was not
      apparent when all 7 virulence factors were considered collectively. There was an
      apparent correlation between the genotypes and serotypes of the E. coli strains
      from the cystitis patients. From the data presented, it was proposed that genetic
      detection of virulence factors would be useful for rapid diagnosis of cystitis,
      especially in patients without severe pyuria or bacteriuria.

PMID- 8551972
TI  - Suppression of anti-Candida activity of murine neutrophils by progesterone in
      vitro: a possible mechanism in pregnant women's vulnerability to vaginal
      candidiasis.
AB  - Sex steroid hormones were examined for their effect on mycelial growth of Candida
      albicans, and the inhibitory activity of casein-induced murine peritoneal
      neutrophils against mycelial growth of C. albicans was examined in vitro using a
      crystal violet staining method or a [3H]glucose incorporation method. Four
      steroid hormones, danazol, estradiol, estriol and testosterone had no effect on
      mycelial growth of C. albicans, but progesterone appeared to convert the growth
      form of C. albicans from hyphal to yeast. Danazol (10(-6) M) and progesterone
      (10(-5) M) suppressed anti-Candida activity of neutrophils of non-treated mice,
      while testosterone, estradiol, and estriol did not. The anti-Candida activity of
      neutrophils of estradiol-pretreated mice was clearly suppressed by progesterone
      even at 10(-6) M which corresponded to its plasma concentration in pregnant women
      in the third trimester. The physiological significance of this suppressive effect
      of progesterone was discussed in relation to the vulnerability of pregnant women
      to vaginal candidiasis.

PMID- 8551973
TI  - Production of tumor necrosis factor-alpha in granulocytopenic mice with pulmonary
      candidiasis and its modification with granulocyte colony-stimulating factor.
AB  - In the present study, a lethal model of pulmonary candidiasis was established
      using granulocytopenic mice with cyclophosphamide. These mice started to die 1
      day after infection and had all died within the next 48 hr. The counts of live C.
      albicans in the lung gradually increased with time, while the organisms were
      quickly eliminated in the normal mice. From the histology and measurements on
      bronchoalveolar lavage fluid (BALF), polymorphonuclear cells (PMN) response was
      almost zero up to 24 hr; and then a weak but significant response was observed at
      48 hr, while a marked accumulation of PMN was detected from as early as 6 hr in
      normal mice. In contrast, macrophages had accumulated in BALF by 48 hr in
      granulocytopenic mice, but not in normal mice. Both in serum and BALF, a
      considerable level of tumor necrosis factor-alpha (TNF-alpha) was detected from 6
      hr, peaking at 24 to 48 hr, while in normal mice the quantity was under the
      detection limit in serum and very low in BALF. The effects of administering
      granulocyte colony-stimulating factor (G-CSF) on these parameters were next
      examined. G-CSF significantly prolonged the survival time of granulocytopenic
      mice, promoted the clearance of organisms through increasing the counts of PMN in
      the lung, and strongly inhibited the production of TNF-alpha both in BALF and
      serum. These results suggest that this cytokine does not protect them, but plays
      some role in their death due to candidial infection in granulocytopenic mice.

PMID- 8551974
TI  - Prevalence of antibodies to Borrelia spirochetes among wild small rodents in
      central and western Japan.
AB  - Field rodents serve as a reservoir for Lyme disease spirochetes. To evaluate the
      antibody responses of rodents against different Borrelia species in relation to
      fauna of vector ticks feeding on them, we examined 272 sera of wild rodents,
      Apodemus speciosus, A. argenteus, and Eothenomys smithii, obtained in 27
      locations in central and western Japan from 1981 to 1994. As to prevalences by
      rodent species using immunoperoxidase test, A. speciosus, A. argenteus and E.
      smithii showed 29.4%, 11.6% and 30.8% reactivity to Borrelia japonica, 10.7%,
      7.2% and 3.8% to B. afzelii, 0.6%, 1.4% and 0% to B. garinii, and 14.7%, 7.2% and
      11.5% to an unknown Borrelia species designated as It type, respectively. Each
      antibody to B. japonica, B. afzelii and B. sp. It type was detected widely both
      in central and western Japan, but the antibody to B. garinii was scarcely
      detectable in any area and rodent species examined. Apodemus mice in high
      mountain altitudes tend to have antibody to B. afzelii or B. japonica, and those
      in lower altitudes tend to have B. japonica or B. sp. It type. All 13 Apodemus
      mice from which B. japonica or B. sp. It type were isolated showed higher titers
      of antibodies to each homologous Borrelia species. The present results indicate
      that these antibody prevalences among rodents may be associated with dominant
      Ixodes ovatus and sporadic I. persulcatus on the mainland of Japan, and that
      Apodemus mice may not be an efficient reservoir for B. garinii. Such a serosurvey
      is a useful measure to evaluate the natural distribution of the pathogen.

PMID- 8551975
TI  - Salt-induced L-forms of Staphylococcus aureus.
AB  - When growing cultures of a salt-sensitive strain of Staphylococcus aureus were
      inoculated on nutrient agar containing 0.8 M NaCl and 0.5% bovine serum albumin,
      typical colonies of L-form developed extensively after 2 days of incubation at 30
      C. Incubation of growing cultures with lipoteichoic acid, sodium polyanethole
      sulfonate and subtilisin resulted in inhibition of L-form induction.

PMID- 8551976
TI  - Nucleotide sequence analysis of recent epidemic strains of enterovirus 70.
AB  - Nucleotide sequences of the genome of enterovirus 70 (EV70) isolated in Osaka in
      1993 were determined, and compared with those of the past epidemic strains.
      Nucleotide substitution rates in 332 bp, 174 bp, and 178 bp of the genes encoding
      viral protein (VP)1, VP2, or VP3 were 9.0, 7.5, and 5.6% between Kumoi-2/93 and
      J670/71, respectively. Likewise, the putative amino acid substitution rates were
      1.8, 0, and 0%. It seems that the epidemic strains of EV70 in Japan have been
      evolving at a constant high nucleotide substitution rate but almost all the
      substitutions were synonymous.

PMID- 8551977
TI  - Isolation of cytopathic small round virus (Aichi virus) from Pakistani children
      and Japanese travelers from Southeast Asia.
AB  - Aichi virus was isolated in Vero cells from 5 (2.3%) of 222 Pakistani children
      with gastroenteritis but none was found in 91 healthy children. Aichi virus was
      also isolated from 5 (0.7%) of 722 Japanese travelers returned from tours to
      Southeast Asian countries and complained of gastrointestinal symptoms at the
      quarantine station of Nagoya International Airport in Japan. Of 5 Japanese
      travelers, 3 were returning from Indonesia, and 2 from Thailand or Malaysia.
      These results indicate that Aichi virus or a similar agent is endemic in
      Southeast Asian countries and is a cause of gastrointestinal symptoms in children
      in these areas or in Japanese travelers who visit there.

PMID- 8551978
TI  - New drugs for osteoporosis.

PMID- 8551979
TI  - Valacyclovir.

PMID- 8551980
TI  - Computer-aided detection of mammographic microcalcifications: pattern recognition
      with an artificial neural network.
AB  - We are developing a computer program for automated detection of clustered
      microcalcifications on mammograms. In this study, we investigated the
      effectiveness of a signal classifier based on a convolution neural network (CNN)
      approach for improvement of the accuracy of the detection program. Fifty-two
      mammograms with clustered microcalcifications were selected from patient files.
      The clusters on the mammograms were ranked by experienced mammographers and
      divided into an obvious group, an average group, and a subtle group. The average
      and subtle groups were combined and randomly divided into two sets, each of which
      was used as training or test set alternately. The obvious group served as an
      additional independent test set. Regions of interest (ROIs) containing potential
      individual microcalcifications were first located on each mammogram by the
      automated detection program. The ROIs from one set of the mammograms were used to
      train CNNs of different configurations with a back-propagation method. The
      generalization capability of the trained CNNs was then examined by their accuracy
      of classifying the ROIs from the other set and from the obvious group. The
      classification accuracy of the CNNs for the ROIs was evaluated by receiver
      operating characteristic (ROC) analysis. It was found that CNNs of many different
      configurations can reach approximately the same performance level, with the area
      under the ROC curve (Az) of 0.9. We incorporated a trained CNN into the detection
      program and evaluated the improvement of the detection accuracy by the CNN using
      free response ROC analysis. Our results indicated that, over a wide range of true
      positive (TP) cluster detection rate, the CNN classifier could reduce the number
      of false-positive (FP) clusters per image by more than 70%. For the obvious
      cases, at a TP rate of 100%, the FP rate reduced from 0.35 cluster per image to
      0.1 cluster per image. For the average and subtle cases, the detection accuracy
      improved from a TP rate of 87% at an FP rate of four clusters per image to a TP
      rate of 90% at an FP rate of 1.5 clusters per image.

PMID- 8551981
TI  - Analysis of spiculation in the computerized classification of mammographic
      masses.
AB  - Spiculation is a primary sign of malignancy for masses detected by mammography.
      In this study, we developed a technique that analyzes patterns and quantifies the
      degree of spiculation present. Our current approach involves (1) automatic lesion
      extraction using region growing and (2) feature extraction using radial edge
      gradient analysis. Two spiculation measures are obtained from an analysis of
      radial edge gradients. These measures are evaluated in four different
      neighborhoods about the extracted mammographic mass. The performance of each of
      the two measures of spiculation was tested on a database of 95 mammographic
      masses using ROC analysis that evaluates their individual ability to determine
      the likelihood of malignancy of a mass. The dependence of the performance of
      these measures on the choice of neighborhood was analyzed. We have found that it
      is only necessary to accurately extract an approximate outline of a mass lesion
      for the purposes of this analysis since the choice of a neighborhood that
      accommodates the thin spicules at the margin allows for the assessment of margin
      spiculation with the radial edge-gradient analysis technique. The two measures
      performed at their highest level when the surrounding periphery of the extracted
      region is used for feature extraction, yielding Az values of 0.83 and 0.85,
      respectively, for the determination of malignancy. These are similar to that
      achieved when a radiologist's ratings of spiculation (Az = 0.85) are used alone.
      The maximum value of one of the two spiculation measures (FWHM) from the four
      neighborhoods yielded an Az of 0.88 in the classification of mammographic mass
      lesions.

PMID- 8551982
TI  - DQE(f) of four generations of computed radiography acquisition devices.
AB  - Measurements were made of the MTF(f), NPS(f), and DQE(f) of four generations of
      computed radiography (CR) imaging plates and three generations of CR image
      readers. The MTF generally showed only a minor change between generations of
      plates and readers, but the DQE(f) has improved substantially from a very early
      plate/reader combination to a more recent one. The DQE in the more recent
      plate/reader combination is 1.3X greater at low frequencies and about 3X greater
      at high frequencies than the much earlier versions. Thus there has been
      substantial improvement in the imaging performance obtainable with CR since some
      of the early observer studies which indicated poorer performance with CR than
      with screen-film.

PMID- 8551983
TI  - X-ray imaging using amorphous selenium: feasibility of a flat panel self-scanned
      detector for digital radiology.
AB  - We investigate a concept for making a large area, flat-panel detector for digital
      radiology. It employs an x-ray sensitive photoconductor to convert incident x
      radiation to a charge image which is then electronically read out with a large
      area integrated circuit. The large area integrated circuit, also called an active
      matrix, consists of a two-dimensional array of thin film transistors (TFTs). The
      potential advantages of the flat-panel detector for digital radiography include:
      instantaneous digital radiographs without operator intervention; compact size
      approaching that of a screen-film cassette and thus compatibility with existing x
      ray equipment; high quantum efficiency combined with high resolution. Its
      potential advantages over the x-ray image intensifier (XRII)/video systems for
      fluoroscopy include: compactness; geometric accuracy; high resolution, and
      absence of veiling glare. The feasibility of the detector for digital radiology
      was investigated using the properties of a particular photoconductor (amorphous
      selenium) and active matrix array (with cadmium selenide TFTs). The results
      showed that it can potentially satisfy the detector design requirements for
      radiography (e.g., chest radiography and mammography). For fluoroscopy, the
      images can be obtained in real-time but the detector is not quantum noise limited
      below the mean exposure rate typically used in fluoroscopy. Possible improvements
      in x-ray sensitivity and noise performance for the application in fluoroscopy are
      discussed.

PMID- 8551984
TI  - Photoacoustic ultrasound (PAUS)--reconstruction tomography.
AB  - The theoretical underpinnings of photoacoustic ultrasound (PAUS) reconstruction
      tomography are presented. A formal relationship between PAUS signals and the
      heterogeneous distribution of optical absorption within the object being
      investigated is developed. Based on this theory, a reconstruction approach,
      analogous to that used in x-ray computed tomography, is suggested. Initial
      experimental results suggest that this approach produces "reasonable"
      reconstructions for absorbers distributed within a narrow plane embedded within a
      highly scattering medium.

PMID- 8551985
TI  - Quantitation of organ symmetry by diagnostic ultrasonic imaging: a group
      theoretical approach.
AB  - A method based on group theory is proposed to quantify the shape of an organ. It
      is proposed that a complex shape is characterized by a basic set of symmetry
      operations involving rotation about the center axis. Based on this concept,
      partial symmetry elements (PSE) were determined by stepwise rotation of the
      images and measurement of overlap area between the original and rotated images.
      These measurements were used to define a symmetry index (SI) and to "decompose"
      the complex shape into simpler shapes with regular geometry such as a circle, an
      ellipse, an equilateral triangle, a square, etc. Computer simulations and two
      dimensional (2-D) ultrasonic images of the prostate were used to demonstrate the
      feasibility of the method. The method was also applied to a series of clinical
      ultrasonic cardiac images to determine the dynamic shape changes in left
      ventricle (LV) of a normal heart and an heart with infarction. The results of
      this study show that SI increased with an increase in the symmetry of the
      simulation models and the prostate. Cross-sectional images of prostate with
      triangular and ellipsoidal shapes exhibited larger proportion of three-fold and
      two-fold symmetries, respectively. Symmetry index of the LV changed during the
      cardiac cycle and exhibited a loop-like structure when plotted as a function of
      size. Quantitative measurements of SI indicated that the left ventricular chamber
      is rounder during the diastolic phase of the cardiac cycle. The loop-like
      structure was considerably reduced in the heart with infarction. Also, larger
      distortions in cardiac shape were observed over cardiac cycle in the heart with
      infarction, as compared to the normal heart. In conclusion, it is feasible to
      quantitatively characterize 2-D shapes of the organs by symmetry operations based
      on group theoretical analysis.

PMID- 8551986
TI  - On the correction for radioactive decay in pharmacokinetic modeling.
AB  - The question of how to include radioactive decay during biological modeling with
      first-order differential equations was considered. Modeling may involve either
      experimental data y(t) or decay-corrected data z(t) [identical to exp(lambda
      t)y(t) where lambda is the decay constant] for each compartment. It is sometimes
      assumed that the latter are solutions to corresponding purely pharmacokinetic
      models (no decay). We primarily compared the two analyses in the case where the
      model did not require simultaneous consideration of both labeled and unlabeled
      material. A general theorem was found which limits the use of decay-corrected
      data to pharmacokinetic models containing linear, homogeneous differential
      equations. By way of verification, an example of this model type was analyzed for
      a chimeric monoclonal antibody biodistribution in man. Even in this case,
      statistically significant differences between the two solutions showed that one
      may find different model parameters depending upon which data set (y or z) was
      analyzed. For other mathematical forms, the analyst must include the physical
      decay in all relevant compartments. By analyzing an open, quadratic model,
      effects of not including decay were seen to be maximized if the biological rate
      constant was > or = lambda, the physical decay constant. Finally, using
      monoclonal antibody-antigen reactions, similar discrepancies between the z
      functions and the pharmacokinetic variables were demonstrated. This result was
      found to persist even if competitive molecules were included. We conclude that
      decay-corrected data may be shown, but should not be entered into the modeling
      equations unless the latter are of the linear, homogeneous form.

PMID- 8551987
TI  - A transmission-map-based scatter correction technique for SPECT in inhomogeneous
      media.
AB  - In this paper a method of modeling the distribution of scattered events in
      emission projection data is developed and applied. This method is based on the
      use of a transmission map to define the inhomogeneous scattering object. The key
      point is the use of the set of line integrals calculated as part of the
      attenuation correction technique, as the basis of a model of the distribution of
      scattered events. The probability of a photon being scattered through a given
      angle and being detected in the emission energy window is approximated using a
      Gaussian function. The parameters of this Gaussian are determined using Monte
      Carlo generated parallel-beam scatter line spread functions from a nonuniformly
      attenuating phantom. The model is incorporated into a two-dimensional projector
      backprojector and used with the Expectation-Maximization-Maximum-Likelihood
      algorithm for the reconstruction of fan-beam phantom data. The correction is
      shown to perform well for a phantom that varies slowly in the axial direction.
      For the more clinically realistic situation of a torso phantom, the method
      produces improvements in terms of blood pool to myocardium contrast, but does not
      restore the contrast to the level exhibited in a reconstruction from "scatter
      free" data.

PMID- 8551988
TI  - Improved conjugate view quantitation of I-131 by subtraction of scatter and
      septal penetration events with a triple energy window method.
AB  - The majority of radiation absorbed dose estimates for radioimmunotherapy (RIT)
      with I-131 labeled antibodies have been calculated based on in vivo quantitation
      of activity using the conjugate view approach with planar Anger camera images.
      Scatter and septal penetration events contributed by a small fraction of high
      energy photons emitted by I-131 with an energy exceeding 600 KeV lead to a
      significant degradation of I-131 images acquired with an Anger camera, which
      blurs the images of uptake sites and complicates the definition of background
      regions. The objective of this study was to evaluate a triple energy window (TEW)
      subtraction method that has been used to remove these interfering events from I
      131 images. In the method, a primary photopeak image for I-131 is obtained after
      sequential subtraction of septal penetration and scatter events by using scatter
      multipliers derived from a photopeak window and two adjacent scatter window
      images. Qualitative improvement in image contrast was demonstrated with this
      technique, together with more accurate and reproducible quantitation for I-131 in
      the organs of an abdominal phantom. This TEW scatter subtraction method can be
      used to provide more precise dosimetry estimates for radionuclide therapy and RIT
      with I-131.

PMID- 8551989
TI  - Correcting for rf inhomogeneities in multiecho pulse sequence MRI dosimetry.
AB  - The growing interest in using MRI to measure distributions of dose in specialized
      materials has prompted the need to improve existing methods for measuring NMR
      relaxation rates throughout large volume phantoms. The change in transverse
      relaxation rate (R2) has proven to be a more sensitive measure of dose than
      longitudinal relaxation rate (R1) in some materials; however, the accuracy of R2
      measurements is limited by the presence of artifacts resulting from imperfect MRI
      tip angles throughout large phantoms. A novel echo quotient technique allowing
      accurate measurement of changes in R2 (delta R2) in regions of imperfect tip
      angle is presented. Application of this technique to the measurement of a
      dynamically wedged photon beam dose distribution demonstrates the improved
      accuracy of the echo quotient technique compared with other methods. Agreement of
      the MRI data with film and ion chamber data is within 2.5% throughout the volume
      of interest, indicating the potential for delta R2 MRI dosimetry to become a
      clinically useful tool.

PMID- 8551990
TI  - Optimization of MR pulse sequences for Bayesian image segmentation.
AB  - A method for optimizing MR imaging pulse sequence parameters in a statistical
      framework is presented. Parameters are defined to be optimal when the resulting
      scalar images yield optimal image segmentations using Bayesian pixel
      classification. Thus, Bayes risk is used as the objective function to minimize.
      Approximations are made to give a tractable solution in a four-step procedure. A
      sample calculation is carried out to determine the optimal TR and flip angle for
      scalar SPGR imaging of the brain. Overall, this paper gives a new approach to
      optimize MRI pulse sequences for the specific objective of improved image
      segmentation.

PMID- 8551991
TI  - Calculation of x-ray spectra for radiosurgical beams.
AB  - As conformal radiosurgery using micromultileaf collimators gains feasibility,
      dose calculation algorithms based on Monte Carlo or convolution techniques may
      become necessary. These require radiosurgical x-ray spectra. The most accurate
      method currently available to estimate clinical radiosurgery spectra is the Monte
      Carlo method. In this study the EGS4 Monte Carlo system was used to simulate the
      thick target of a 6 MV linear accelerator used for radiosurgery in our center.
      The calculated spectrum was attenuated through any significant mass thickness of
      material downstream from the target. The attenuated thick-target spectral
      distributions calculated both with and without the flattening filter were
      compared to the attenuated, thin target spectrum based on the small angle Schiff
      analytical spectrum calculated for the same target and attenuator material, as
      well as with a published spectrum from a full Monte Carlo simulation of a
      treatment head with a flattener in place. The Schiff spectrum neglects
      contributions from lower-energy scattered electrons that significantly degrade
      the quality of the beam. The flattener is removed from our accelerator during
      radiosurgery to increase the dose rate to approximately 750 cGy/min for a 10 x 10
      cm2 field at the depth of dose maximum. This leaves a substantial fluence of
      photons below 1 MeV that are not observed in published spectra calculated for
      accelerators with flattening filters. Removal of the flattening filter has a
      measurable effect on the central axis depth dose, reducing the percentage dose at
      10 cm depth from 59.2% to 54.3% for a 10 mm diam field. Radiosurgical off-axis
      ratios and percentage depth dose distributions calculated from these spectra with
      the EGS4 Monte Carlo code were compared to measured data. Measured and calculated
      dose distributions both with and without flattener were in good agreement. The
      dose distributions were found to be insensitive to the differences in the various
      calculated spectral distributions. Thus, although the attenuated Schiff spectrum
      is significantly harder than the clinical beam, it is adequate for dose
      calculations of radiosurgical beams.

PMID- 8551992
TI  - Deconvolution of detector size effect for small field measurement.
AB  - Parametrization of the small fields employed in stereotactic applications is a
      painstaking process involving extensive film dosimetry to achieve acceptable beam
      edge definition. Use of cylindrical or spherical detectors for profile
      measurements would simplify data acquisition but add a volume averaging artifact
      to beam edge definition. We demonstrate a simple approach to unfolding the
      chamber size artifact from measured small beam profiles using typical cylindrical
      chambers. In comparison with film measurements we have found good agreement when
      the detector response function is deconvoluted from the measured profiles,
      although the amount of correction needed is fairly minimal for the detectors
      studied.

PMID- 8551993
TI  - Electron-beam characteristics at extended treatment distances.
AB  - A uniform dose to the target site is required with a knowledge of delivered dose,
      central axis depth dose, and beam flatness for successful electron treatment at
      an extended source to surface distance (SSD). The central axis depth dose is
      shown to be nearly independent of moderate changes in the treatment distance. The
      delivered dose at a point could be calculated with the concept of virtual source
      position and an inverse square correction. In an extended SSD treatment,
      underdosage of the lateral tissue may occur due to reduced beam flatness. To
      study the changes in beam characteristics, the depth dose and beam flatness were
      measured at different SSDs for clinically used field sizes [(3 x 3)-(15 x 15)
      cm2] and beam energies ranging from 6 to 20 MeV. Our results indicate that the
      changes in depth dose are minimal except in the buildup region for most energies.
      In general, the surface dose is decreased (< or = 10%) as the SSD is increased
      moderately. Beam flatness was measured in terms of target coverage factor (TCF)
      defined as the ratio of the width of a specified isodose line to the geometrical
      field width. It was observed that the loss in beam flatness is significant for
      smaller fields, higher isodose lines, and lower energies. Variations in SSD have
      a minimal effect on the relative changes in beam flatness for field sizes greater
      than 8 x 8 cm2. The lateral loss of beam uniformity could be estimated by various
      parameters, such as the full width at half maximum, the homogeneity index, the
      uniformity index, and the TCF; however, TCF is a simpler parameter to use
      clinically. The beam characteristics (depth dose and TCF) at extended treatment
      distances are presented for electron beams.

PMID- 8551994
TI  - Depth dose flattening of electron beams using a wire mesh bolus.
AB  - A common problem with low-energy electron beams (< 15 MeV) is their low surface
      dose when the incident electrons are monodirectional. This makes it difficult to
      deliver a uniform dose to tumor with any precision, limiting the clinical
      usefulness of such beams. A practical method is presented for greatly increasing
      the tissue depth enclosed by the 95% isodose region, while delivering the entire
      dose in a single uninterrupted treatment. Beam modification is achieved by
      placing a wire mesh of high atomic number (Z) on the treatment surface throughout
      the treatment. Electron beams of energies 6, 9, and 13 MeV are modified to
      produce a near uniform dose from the surface to the original depth of maximum,
      approximately doubling the depth enclosed by the 95% isodose. These beams have a
      step-function-like depth dose and can be arranged to deliver a constant dose to
      tumor located at varying depths while simultaneously sparing deeper tissues which
      are also located at varying depths. A single mesh design was found to be suitable
      for all energies.

PMID- 8551995
TI  - Calculation of dose distributions in the vicinity of high-Z interfaces for photon
      beams.
AB  - In the vicinity of interfaces between materials of different atomic number Z,
      extremes in absorbed dose occur for high-energy photon irradiations. The spatial
      extension of the effects is within the range of 1 cm, which may not be ignorable
      from the radiobiological point of view. At the front side of a high-Z slab a
      maximum is observed, whereas at the exit side a small buildup zone of the dose
      occurs, e.g., for a 5 MV beam, in front of a water/iron interface, the
      enhancement is about 30% of that to the homogeneous medium. The reduction at the
      back of the iron slab is about 16% for this energy, but vanishes with increasing
      energy. For high-energy photons this effect is mainly caused by the strong atomic
      number dependence of the scattering power for secondary electrons. The amount and
      extent of the scattering effects have been measured for aluminum and for iron
      slabs embedded in water or PMMA. The experimental data are in good agreement with
      Monte Carlo calculated values. Therefore the data form a reliable base to test
      the performance of commonly used treatment planning algorithms. The convolution
      or superposition method is used to calculate dose distributions. To account for
      the Z dependence of the scattering and the stopping power of the secondary
      electrons, corrections are applied to the energy deposition kernels. The boundary
      crossing of energy deposition kernels can be treated only in an approximate
      manner. However, the algorithm developed improves the accuracy of the dose
      calculation in the vicinity of interfaces significantly.

PMID- 8551996
TI  - Radiation protection requirements for medical x-ray film.
AB  - Previous darkroom shielding requirements for medical x-ray film-assumed that the
      film should not be exposed to diagnostic x-ray radiation levels greater than 2
      microGy (0.2 mR) for the life of the film. Modern medical x-ray films are much
      less sensitive to ionizing radiation, with most films showing at least an order
      of magnitude less sensitivity than previously assumed. Conversely, these same
      films when loaded in cassettes using modern intensifying screens exhibit an order
      of magnitude greater sensitivity when these cassettes are exposed to ionizing
      radiation. These data suggest that protection of modern medical x-ray film,
      stored in a darkroom, may require less shielding than previously assumed.
      Conversely, film loaded in a cassette will require greater shielding.

PMID- 8551997
TI  - Comment on "Characterization of vertebral strength using digital radiographic
      analysis of bone structure" [Med. Phys. 22, 611-615 (1995)].

PMID- 8551998
TI  - Magnetic resonance imaging and spectroscopy in fetal ethanol exposed Macaca
      nemestrina.
AB  - Magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H
      MRS) offer noninvasive ways to observe structural and biochemical changes which
      might serve as valuable diagnostic markers for detecting brain damage from
      prenatal ethanol teratogenesis. Cranial MR imaging and spectroscopy were
      performed on 20 nonhuman primates (Macaca nemestrina) with known prenatal ethanol
      exposures and well-documented cognitive and behavioral levels of performance. The
      choline: creatine ratio detected by 1H-MRS in the brain increased significantly
      with increasing duration of in utero ethanol exposure. These signal alterations
      occurred in the absence of gross structural brain anomalies (detectable by MRI)
      and were significantly correlated with alcohol-related cognitive and behavioral
      dysfunction. These observations are consistent with reports of elevated choline:
      creatine ratios associated with various neurologic insults and disease states.
      The association observed between brain choline:creatine ratios and in utero
      ethanol exposure suggest a role for 1H-MRS in elucidating mechanisms of ethanol
      teratogenicity.

PMID- 8551999
TI  - Behavioral and neurochemical effects of chronic methylenedioxymethamphetamine
      (MDMA) treatment in rhesus monkeys.
AB  - Effects of chronic treatment with the putative serotonergic neurotoxicant MDMA
      were assessed in rhesus macaques using behavior in an operant test battery (OTB)
      designed to model aspects of time estimation, short-term memory, motivation,
      learning, and color and position discrimination. After an initial acute dose
      response assessment, escalating doses of MDMA (0.10-20.0 mg/kg, im, twice daily,
      for 14 consecutive days at each dose) were administered, followed by three
      additional acute dose-response assessments. In general, tolerance to MDMA's acute
      effects was evident in all OTB tasks by the second week of repeated exposure to
      each individual MDMA dose and as doses escalated. Baseline OTB performance after
      chronic treatment was not significantly altered. Residual behavioral tolerance to
      MDMA's acute effects, however, was evident in all OTB tasks but was least
      pronounced in the motivation task. Monkeys were sacrificed (21 months after
      chronic treatment) and brains were dissected into several regions for
      neurochemical analyses. Serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA),
      dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid
      (HVA) were analyzed via HPLC. Although MDMA-treated monkeys tended to have lower
      5-HT concentrations in the frontal cortex, chronic MDMA treatment had no
      significant effects on 5-HT concentrations in any brain area sampled. Hippocampal
      5-HIAA concentration, 5-HT uptake sites, and turnover of 5-HT of MDMA-treated
      monkeys were significantly lower than control values. DA concentrations in the CN
      of MDMA-treated monkeys were significantly greater than control values. No
      significant effects on DA concentrations were noted in any other brain area
      sampled. The absence of significant decreases in 5-HT and the general increase in
      DA concentrations are dissimilar to neurochemical effects reported after a short
      course of MDMA treatment at relatively high doses. These data suggest that
      chronic administration of gradually increasing doses of MDMA results in long
      lasting tolerance to the drugs acute effects on the complex brain functions
      modeled in the OTB. It is uncertain, however, if such tolerance is related to the
      observed decreases in uptake sites and turnover of 5-HT in the hippocampus of
      these monkeys.

PMID- 8552000
TI  - Prenatal ethanol exposure in rats: long-lasting effects on learning.
AB  - Pregnant Sprague-Dawley rats were fed a liquid diet containing either 0% (group
      C), 18% (group L), or 36% (group H) ethanol-derived calories (EDC) from
      gestational day 1 to 20. Male offspring were assessed under a conditioned taste
      aversion paradigm (PND 35-45), in a complex maze (PND 68-80), and for operant
      behavior (temporal response differentiation and motivation to work for food, PND
      140-198). Although conditioned taste aversion was fully acquired by all groups,
      retention of the conditioned taste aversion response was impaired in group H
      animals. Importantly, deficits in the acquisition of timing behavior were found
      in group H (group L not tested), confirming that this operant task is quite
      sensitive in detecting prenatal drug effects and demonstrating that neurological
      effects of prenatal ethanol exposure persist into late adulthood.

PMID- 8552001
TI  - Adult reactivity in rats exposed to cocaine during two early postnatal periods.
AB  - This study investigated whether exposure to cocaine during two periods of
      postnatal development affects the acoustic startle response (ASR) in adulthood.
      Female rats received 50 mg/kg/day cocaine HCl or vehicle SC during either
      postnatal days 1-10 or 11-20. At 60-65 days of age, subjects were ASR tested for
      30 min on 2 consecutive days. Overall, ASR was increased on day 1 compared to day
      2. Also comparisons between groups within each session and injection schedule
      showed that subjects exposed to cocaine during postnatal days 1-10 exhibited
      increased ASR amplitude on the second day of testing compared to controls. No
      group differences in response latency were observed. Therefore, these data
      indicate that, for female rats, cocaine alters the development of the pathways
      involved in modification of the acoustic startle response in a way consistent
      with a disruption of long-term habituation, but that the critical period for this
      disruption in females is postnatal days 1-10 and not 11-20.

PMID- 8552002
TI  - Comparative effects of prenatal cocaine, alcohol, and undernutrition on
      maternal/fetal toxicity and fetal body composition in the Sprague-Dawley rat with
      observations on strain-dependent differences.
AB  - Pregnant rats received either 20, 30, 40, or 50 mg/kg cocaine HCl (SC) twice
      daily from gestation days 7 through 19. Pair-fed and untreated control groups and
      a group receiving 3.0 g/kg alcohol (PO) twice daily served as comparison groups.
      Females were sacrificed on gestation day 20 and the fetuses examined. Maternal
      weight gain and food consumption showed dose-dependent decreases. Maternal water
      consumption, by contrast, was significantly increased in the cocaine-treated
      animals and may reflect a diuretic effect. The maternal mortality rates in
      Sprague-Dawley rats were less than in two strains of Long-Evans rats, suggesting
      important strain-dependent differences in susceptibility to cocaine toxicity.
      Cocaine caused a significant dose-dependent decrease in fetal weights. Physical
      anomalies in the cocaine-exposed and alcohol-exposed fetuses included occasional
      hemorrhaging, edema, anophthalmia, and limb reduction. Despite increased maternal
      water consumption by cocaine-treated dams, there were no increases in fetal body
      water content. There were, however, significant decreases in fetal body fat
      content in the pair-fed, alcohol-treated, and two highest cocaine-treated groups.

PMID- 8552003
TI  - Prenatal cocaine exposure affects social behavior in Sprague-Dawley rats.
AB  - Children prenatally exposed to cocaine are reported to exhibit inappropriate
      social behavior, including aggression. We have recently observed a similar
      phenomenon in rats prenatally exposed to cocaine. Pregnant females were injected
      twice daily with 15 mg/kg cocaine hydrochloride or saline on gestation days 1-20.
      Offspring were tested for social behavior towards two unfamiliar, untreated rats
      of the same age and sex. Cocaine-treated males (90 PND) took longer to
      reciprocate contact and cocaine-treated females (60 PND) spent more time rough
      grooming unfamiliar females. Male cocaine offspring (180 PND) tested for
      aggression exhibited an increased frequency and duration and decreased latency to
      chase an intruder. ACTH was lower in cocaine-treated males (150-180 PND)
      following plus-maze exposure or exposure to an unfamiliar male. Our data indicate
      that prenatal cocaine treatment in rats increases fear or aggression responses,
      dependent on sex and stimulus situation.

PMID- 8552004
TI  - Acute gestational cocaine exposure alone or in combination with low-dose ethanol
      does not influence prenatal mortality or fetal weight in mice.
AB  - The teratogenic effects of cocaine and ethanol were investigated using an acute
      treatment model of C57BL/6J mice treated on gestation day 15 (GD15) with
      evaluation on GD17. Females were intubated once with a subteratogenic dose of
      ethanol (0 or 4 g/kg) and injected subcutaneously twice, 1 h apart, with equal
      doses of cocaine HCl (0 or 60 mg/kg), for a final daily dose of 120 mg/kg. The
      first cocaine injection followed ethanol by 10 min. Blood ethanol levels (BEL)
      and plasma cocaine levels were determined, and pair-feeding was employed. The
      results revealed no group differences on pregnancy outcome. That is, maternal
      weight gain, total number of implants, prenatal mortality, and fetal body weight
      were not statistically different. No significant differences in BEL or plasma
      cocaine levels were found among the various treatment groups. These results
      suggest that, under these conditions, relatively high levels of cocaine (120
      mg/kg, SC), given alone or in combination with subteratogenic doses of ethanol
      late in pregnancy, are not teratogenic in mice.

PMID- 8552005
TI  - Behavioral teratology and dominant lethal evaluation of nitrous oxide exposure in
      rats.
AB  - Epidemiological studies have suggested that spontaneous abortion may be increased
      in medical personnel following the sort of chronic low-level exposure to the
      anesthetic gas nitrous oxide (N2O) seen in surgical or dental operatories. These
      results are supported by some, but not all, animal studies, and results are less
      well established at low exposure levels. Behavioral effects in exposed animal
      offspring have also been observed, but again not in all studies. To further
      examine this problem, we conducted the present experiments. Adult male or female
      rats were exposed to trace concentrations of N2O (0%, 0.1%, 0.5%, or 1.0% in air)
      for 6 h daily either throughout gestation (females) or for 9 weeks (males).
      Offspring from treated adults were subjected to an extensive behavioral test
      battery. There were no clear dose-response effects on any of eight behavioural
      tests for any offspring. Maternal and offspring weights were normal from
      conception through adulthood. Additionally, we studied effects of N2O on male
      fertility by mating treated males with untreated females and examining uterine
      contents. There was no evidence for a substantial decline in fertility of exposed
      males, although there was a small dose-related trend for resorptions to increase
      and live births to decrease with increasing paternal N2O exposure. There results
      suggest that there is little alteration in male or female fertility following
      chronic exposure to low levels of N2O. There are also no significant long-term
      behavioral alterations in offspring exposed gestationally to trace levels of N2O
      via dam or sire.

PMID- 8552006
TI  - The effects of cocaine exposure prior to and during pregnancy in rats fed low or
      adequate protein diets.
AB  - Sprague-Dawley rats were fed a diet of low protein content (6% casein), an
      isocaloric diet of adequate protein content (25% casein), or a laboratory chow
      diet for 5 weeks prior to mating and throughout pregnancy. Within each diet
      group, rats received either cocaine (30 mg/kg IP two times per week prior to
      mating and 30 mg/kg or 40 mg/kg SC daily from days 3 to 18 of pregnancy) or
      saline injections. Cocaine produced a greater reduction in food intake during
      pregnancy in the malnourished group compared with the other two diet groups. The
      effect of cocaine on food intake was minimal in chow-fed rats. Weight gain in
      pregnancy was reduced by cocaine in a dose-dependent manner, and by malnutrition.
      Both prenatal cocaine and malnutrition impaired skeletal maturation of the pups,
      but there was no additive effect of the two insults on this measure. Litter size
      was significantly reduced by the 40 mg/kg, but not by the 30 mg/kg dose of
      cocaine across all diet groups. Consequently, the 40 mg/kg dose of cocaine proved
      to be fetotoxic in this model. Birth weight was significantly reduced by prenatal
      malnutrition but not by prenatal cocaine. Gestation length was unaffected by
      either insult. Hence, the ability to detect a diet x drug interaction was
      dependent upon the variable being measured.

PMID- 8552007
TI  - Prenatal cocaine but not prenatal malnutrition affects foster mother-pup
      interactions in rats.
AB  - The separate and combined effects of prenatal cocaine exposure and malnutrition
      on mother-pup interactions in rats were assessed daily from postnatal day 2 to
      day 21. Sprague-Dawley dams were fed a diet of low protein content (6% casein),
      an isocaloric diet of adequate protein content (25% casein, control), or a
      laboratory chow diet prior to mating and throughout pregnancy. Within each diet
      group, rats received either cocaine injections (30 mg/kg IP two times per week
      prior to mating and then 30 mg/kg SC daily from days 3 to 18 of pregnancy) or
      saline injections. Litters were fostered on the day of birth to control mothers
      (i.e., nondrug-exposed dams fed the control or chow diet). Foster mothers fed the
      25% casein diet showed increased contact with cocaine-exposed pups compared with
      nondrug-exposed pups in the second postnatal week but lower levels as the pups
      approached weaning. Passive nursing was increased in dams caring for prenatally
      malnourished, cocaine-exposed pups compared with those caring for similar pups
      with no drug exposure. Chow-fed mothers did not differ in their behavior towards
      pups with or without prenatal cocaine treatment. Prenatal cocaine and
      malnutrition independently compromised birth weight and various reflexive
      milestones but the attainment of physical milestones was affected only by
      prenatal cocaine. There were no additive effects of the two prenatal insults on
      any measure of mother-pup interaction or pup development.

PMID- 8552008
TI  - HIV/AIDS and nutrition in the 1990s.

PMID- 8552009
TI  - A review of mechanisms of wasting in HIV disease.
AB  - According to estimates, between 50% to 90% of patients infected with the Human
      Immunodeficiency Virus (HIV) will experience some form of malnutrition. The
      degree and types of malnutrition are attributed to alterations in nutrient
      intake, absorption, and metabolism. Causes for each of these changes are complex
      and multifactorial. Research on treatment modalities generally concentrates on a
      single mechanism and reports varying degrees of short-term benefit. Appetite
      stimulation along with special diets, oral supplements, and nonvolitional enteral
      or parenteral nutrient provision may improve nutrient intake and body weight.
      Therapies aimed at the rehabilitation and improvement of the pool of functioning
      protein stores, such as alteration of inflammatory response, restoration of
      hormonal balance, and exercise are under investigation. Longer term studies will
      allow researchers to observe effects of therapies on overall body functions. With
      the development of clinical standards of care, the maintenance and restoration of
      nutritional status is emerging as the foundation for HIV disease management.

PMID- 8552010
TI  - Body composition and nutrition support in pediatrics: what to defend and how soon
      to begin.
AB  - Specialized nutrition support is initiated during hospital care on the assumption
      that sparing the mobilization of body energy reserves is advantageous to
      recovery. The combined effects of disease and undernutrition on body cell mass,
      organ function, immune responsiveness, and wound healing are well documented in
      adults. Children cannot survive a fast as long as adults because of their lesser
      stores of energy substrates relative to the rate of energy expenditure. The
      present contribution attempts to estimate the rates of compositional losses for
      infants and prepubertal children on the basis of available data and reasonable
      metabolic assumptions. The lesson that emerges from this exercise is one of a
      very critical need for the early initiation of nutrition support for infants and
      children. The analysis suggests that an acute risk of protein depletion exists
      for children of all ages. Especially for infants, the empirical wisdom that "the
      absence of evidence is not evidence of absence" should be invoked to support
      early nutrition intervention. This work is submitted for critical review and
      revision to establish a consensus on the timeline of pediatric morbidity or
      mortality from semistarvation or starvation.

PMID- 8552011
TI  - Treatment of anorexia nervosa with total parenteral nutrition.
AB  - Recently, there has been a resurgence of interest and ideas regarding refeeding
      in anorexia nervosa. Given the severe morbidity, a subpopulation that appears
      refractory to treatment, and the very high mortality in an otherwise healthy
      young population, research studies are needed to define optimal treatment
      regimens. The authors describe their experience with total parenteral nutrition
      in the treatment of anorexia nervosa.

PMID- 8552012
TI  - The prevalence of nausea and vomiting in pediatric patients receiving home
      parenteral nutrition.
AB  - We have observed that many home parenteral nutrition (HPN) recipients experience
      nausea, vomiting, or both during cyclic parenteral nutrition infusions. The
      current investigation was performed to determine the prevalence and course of
      these symptoms and effectiveness of therapeutic maneuvers. Eighty-nine recipients
      of HPN were contacted and 53 families (60%) responded. Thirty-five patients (66%)
      reported complaints of nausea, vomiting, or both associated with their HPN
      infusion. Patients with cancer (82%) or cystic fibrosis (83%) reported symptoms
      at similar rates, while patients with gastrointestinal disease (46%) reported
      symptoms less often (p < .05, chi-square). Within each diagnostic group,
      prevalence of symptoms did not vary with age. The majority of patients were
      symptomatic in the morning when being weaned or soon after completing the HPN
      infusion. Response rates to a variety of therapies were also similar. In
      conclusion, nausea and vomiting associated with cyclicHPN infusions appear to be
      common. The precipitating events and efficacy of interventions await
      identification and prospective evaluation.

PMID- 8552013
TI  - Glucose metabolism in the neonate: the short and sweet of it.
AB  - Many patients the neonatal nurse cares for daily have the potential for abnormal
      blood glucose levels. Recognizing infants at risk can facilitate timely and
      appropriate interventions. The quality of the information received from tests and
      observation depends on decisions made by the nurse. Therefore, knowledge of
      glucose kinetics and monitoring techniques is essential.

PMID- 8552014
TI  - The utility of a bilateral breast pumping system for mothers of premature
      infants.
AB  - Mothers of premature infants have difficulty maintaining their milk supply as a
      result of the separation that occurs between the mother and the baby. The
      hypothesis in the present investigation is that use of a bilateral (simultaneous)
      breast pumping system will increase the volume of milk expressed in these
      mothers. Thirty-two breastfeeding mothers of premature infants were randomly
      assigned to either the control (single) or the experimental (bilateral) breast
      pump group. Mothers pumped at least four times a day. Data collection included a
      daily milk production log, weekly serum prolactin levels, and a weekly State
      Trait Anxiety Inventory (STAI). Participation lasted from four to six weeks. Data
      analysis included average STAI scores; average prolactin levels; and weekly
      averages for number of pumping sessions, hours of pumping, and milk production in
      milliliters. The two groups did not differ on several demographic
      characteristics, STAI scores, prolactin levels, number of pumping sessions per
      week, or weekly milk production. The amount of time spent pumping, however, was
      statistically less for mothers who used the bilateral pump (7.6 +/- 3.0
      hours/week) versus those who used the single pump (11.1 +/- 3.1 hours/week) (p =
      .003). Although use of either the single pump or the bilateral electric pump
      resulted in similar milk production, the bilateral pump significantly reduced the
      time invested in pumping. Health professionals should advocate use of the
      bilateral pump for mothers of premature infants. Additional studies are needed to
      determine strategies for increasing milk production in this population.

PMID- 8552015
TI  - Recent advances in home infant apnea monitoring.
AB  - Appropriate and effective nursing intervention is an essential element in
      determining how the family responds to the monitor in the home. Accurate
      assessment of the family system and dynamics provides the basis for a plan of
      care. The family's and infant's specific needs must be addressed. Careful
      implementation of the plan allows for changes and unexpected outcomes. Frequent
      evaluation of monitoring is necessary to determine if a change in the plan of
      care is needed. Recent changes in home apnea monitoring technology are rapidly
      altering the care of infants at risk for apnea and SIDS. The advent of the
      documented or recording monitor has the potential to demystify the events
      occurring while the infant is being monitored. Parents can get answers about
      their infant as quickly as a telephone call. The clinician can differentiate
      between a true and a false alarm and reassure the parents accordingly.
      Documenting false events and shallow-breathing alarms will potentially reduce the
      duration of monitoring, decreasing costs to the entire health care system.
      Documented monitoring is a valuable tool for nurses. For the staff nurse,
      clinical observation can be validated through trending and print out of events
      can be done at the bedside. For the advanced practice nurse, management of care
      can become more efficient through remote monitoring via modem. Patient teaching
      can be followed with immediate feedback. Monitors may assist in allaying anxiety
      in families who have lost children to SIDS or had an unexpected death in a
      previous sibling. Families may feel less anxious about having an "at risk" child
      in the home if the events are continuously being recorded. Length of hospital
      stay may decrease initially, with fewer rehospitalizations. Nursing research in
      these areas is necessary. Evaluating events occurring in the home may also help
      shed light on the enigma of SIDS. Several SIDS deaths have been recorded on
      documented monitors. If we can pinpoint exactly what takes place prior to and
      immediately after a SIDS episode, the enigma that has had physicians puzzled for
      so long may finally begin to unravel.

PMID- 8552016
TI  - Current Canadian neonatal research: memories of a gentle presence.

PMID- 8552017
TI  - Are cover gowns necessary in the NICU for parents and visitors?

PMID- 8552018
TI  - Congenital anomalies of the gastrointestinal tract, Part I: The stomach.

PMID- 8552019
TI  - Parental perceptions of infant transfer from an NICU to a community nursery:
      implications for research and practice.

PMID- 8552020
TI  - Gentamicin.

PMID- 8552021
TI  - Nitric oxide therapy for persistent pulmonary hypertension of the newborn.
AB  - Nitric oxide has recently been introduced to the world of neonatal pulmonary
      medicine. The discovery of endogenous nitric oxide production has stimulated
      extensive research into vascular biology to find the relation of nitric oxide to
      the transition of circulatory patterns at birth. Persistent pulmonary
      hypertension of the newborn (PPHN) has long been recognized as a neonatal
      complication to a variety of disorders. Traditional treatments for PPHN have been
      associated with adverse effects. Nitric oxide is considered the only selective
      pulmonary vasodilator to date. Nitric oxide therapy does not produce systemic
      hypotension, often associated with the use of intravenous vasodilators. This new
      therapy may possibly reduce or eliminate the need for invasive life-saving
      procedures such as extracorporeal membrane oxygenation. This article discusses in
      great detail nitric oxide chemistry and physiology and the procedure for nitric
      oxide delivery by inhalation and reviews the results of recent research.

PMID- 8552022
TI  - Surveillance for injuries and illnesses and rapid health-needs assessment
      following Hurricanes Marilyn and Opal, September-October 1995.
AB  - Hurricanes rated a category three or greater (on a scale of one to five) strike
      the United States or its territories approximately once every 1.5 years (1). In
      1995, both a category two and category three hurricane struck the United States
      within 18 days, causing approximately 40 deaths (2). This report summarizes the
      surveillance for injuries and illnesses and a rapid health-needs assessment
      conducted after the storms.

PMID- 8552023
TI  - Occupational blood lead survey--Armenia, 1991 and 1993.
AB  - The risk for lead exposure and lead poisoning is a persistent problem for some
      workers (1) and is an important issue in both industrialized and developing
      countries (2). In Armenia, where lead is used widely in industry (3), the
      Armenian Engineers and Scientists of America, Inc. (AESA), and the United
      Armenian Fund (UAF)* initiated a program in 1991 to use blood lead determinations
      to investigate lead exposures, identify industries and circumstances associated
      with lead hazards, and define specific jobs characterized by excessive exposures
      that increase the risk for lead poisoning of workers. In 1991, team investigators
      surveyed four factories that use lead; in 1993, one of the factories was
      resurveyed. Because the capacity of laboratories in Armenia to reliably determine
      blood lead levels (BLLs) is limited, blood specimens were transported to the
      United States for lead testing. This report presents the findings of both surveys
      and establishes the feasibility of sample collection at remote sites for
      transport to laboratories equipped and certified to process lead specimens.

PMID- 8552024
TI  - Progress toward elimination of neonatal tetanus--Egypt, 1988-1994.
AB  - Neonatal tetanus (NT) is a leading cause of neonatal mortality in many parts of
      the world and, of vaccine-preventable diseases, is second only to measles
      worldwide as a cause of childhood mortality (1). In Egypt, although tetanus
      toxoid (TT) vaccination for pregnant women was introduced in 1973, a nationwide
      survey in 1986 estimated that the NT mortality risk was seven per 1000 live
      births (2); in 1987, only 9% of pregnant women received at least two doses of TT
      (TT2+) through the routine vaccination program. Consequently, in 1988, the
      Ministry of Health initiated an aggressive NT elimination program; this program
      included 1) annual nationwide TT vaccination campaigns during 1988-1993 targeting
      pregnant women, and 2) supplementary campaigns during 1992-1994 targeting all
      women of childbearing age in districts where NT rates were highest. This report
      describes efforts to eliminate NT in Egypt that resulted in an 85% decline in
      reported cases during 1988-1994.

PMID- 8552025
TI  - Overexpression of the RNR1 gene rescues Saccharomyces cerevisiae mutants in the
      mitochondrial DNA polymerase-encoding MIP1 gene.
AB  - A multicopy suppressor gene which rescues the temperature-sensitive growth defect
      of Saccharomyces cerevisiae mutants in the mitochondrial DNA (mtDNA) polymerase
      encoding MIP1 gene has been isolated and identified as the RNR1 gene. This gene,
      whose transcript is cell cycle-regulated and mainly expressed at the G1 to S
      phase transition, encodes the large subunit of ribonucleotide reductase. This
      enzyme catalyses a limiting step in the production of deoxynucleotides needed for
      DNA synthesis. The presence of a high copy number of the RNR1 gene also decreases
      the accumulation of rho- mutants observed in diploids that harbour a single copy
      of the MIP1 gene. In cell cycle-synchronised cells, the presence of a high copy
      number of RNR1 does not modify its cell cycle transcription regulation and
      increases its transcript level by a factor of 10 throughout the cell cycle. Our
      results show that an increased supply of dNTPs in mitochondria can stimulate the
      mtDNA polymerase activity and indicate that the dNTP concentration may be rate
      limiting for the replication of mtDNA.

PMID- 8552026
TI  - Ti plasmid-encoded octopine and nopaline catabolism in Agrobacterium:
      specificities of the LysR-type regulators OccR and NocR, and protein-induced DNA
      bending.
AB  - The occ and noc regions in octopine and nopaline Ti plasmids, respectively, are
      responsible for the catabolism of octopine and nopaline in Agrobacterium. The
      functions are activated in the presence of the opines by OccR and NocR, two
      related regulatory proteins, and the promoters contain common sequence motifs. We
      have investigated heterologous interactions between the regulators and the
      promoters. Previous experiments using all possible heterologous combinations of
      opines, regulators, and promoters in vivo had demonstrated that only the
      combination of nopaline, NocR, and the occ promoter led to limited promoter
      activation. We now show that OccR and NocR bind to the heterologous promoters in
      vitro and in vivo. The weak or non-existent promoter activation actually observed
      could be explained by the assumption that OccR and NocR use different activation
      mechanisms; we investigated protein-induced DNA bending because of reports that
      the two regulators differ in this respect. Analysis with a bending vector showed
      that both OccR and NocR induced a DNA bend that is relaxed in the presence of the
      respective opine. The data suggest that subtle differences in regulator/promoter
      interactions are responsible for the inactivity of the heterologous combinations.
      Investigations with a chimeric NocR/OccR protein indicated that it induced a DNA
      bend in both promoters. No opine-induced relaxation was detectable with the
      hybrid, and the inducible promoter was not activated. These findings suggest that
      bend relaxation may be an integral part of promoter activation.

PMID- 8552027
TI  - H-protein of glycine decarboxylase is encoded by multigene families in Flaveria
      pringlei and F. cronquistii (Asteraceae).
AB  - In Flaveria pringlei and F. cronquistii unlike other plants, H-protein of the
      glycine cleavage system is encoded by small multigene families. From leaf cDNA
      libraries and by reverse transcription of mRNA with subsequent polymerase chain
      reaction (PCR) amplification, we have obtained three different H-protein cDNA
      clones from each species. The relative levels of total H-protein mRNA, as well as
      of different H-protein transcripts, have been determined in leaves, stems, and
      roots of F. pringlei. Stems, with a total of 22% relative to leaves, contain
      substantial amounts of H-protein transcripts. The corresponding level in roots is
      relatively low (2.3% relative to leaves) but easily detectable. One of the
      transcripts occurs only in leaves (HFP20) and another one (HFP13) is present
      exclusively in photosynthesizing organs. Only one of the H-protein transcripts
      (HFP4) was found in all three organs, in leaves, stems, and roots of F. pringlei.

PMID- 8552028
TI  - Structural and functional analysis of the fixLJ genes of Rhizobium leguminosarum
      biovar phaseoli CNPAF512.
AB  - The fixLJ genes of Rhizobium leguminosarum biovar phaseoli CNPAF512 were
      identified by DNA hybridization of a genomic library with an internal fragment of
      the Rhizobium meliloti fixJ gene. The nucleotide sequence was determined and the
      corresponding amino acid sequence was aligned with the amino acid sequences of
      the FixL proteins of R. meliloti, Bradyrhizobium japonicum and Azorhizobium
      caulinodans. While the FixJ protein and the carboxy-terminal part of the FixL
      protein are highly homologous to the other FixL and FixJ proteins, the homology
      in the central heme-binding, oxygen-sensing domain and in the amino-terminal
      domain of FixL is very low. The R. leguminosarum bv. phaseoli FixL protein does
      not contain the heme-binding motif defined for the previously described FixL
      proteins. R. leguminosarum bv. phaseoli fixLJ and fixJ mutants were constructed.
      These mutants can still fix nitrogen, albeit at a reduced level. Expression
      analysis of nifA-gusA and nifH-gusA fusions in the constructed mutants revealed
      that the R. leguminosarum bv. phaseoli fixLJ genes are involved in microaerobic
      nifH expression but not in nifA expression.

PMID- 8552029
TI  - Direct isolation of cDNA sequences from specific chromosomal regions of the
      tomato genome by the differential display technique.
AB  - The differential display technique was originally developed for the isolation of
      differentially expressed genes from eukaryotic tissues. We have adapted this
      technique for the isolation of cDNA markers from specific regions of the tomato
      genome. For this purpose, differential display was performed on RNA extracted
      from leaf tissue of nearly isogenic lines for the Tm-2a gene of tomato. On
      average, one out of 20 primer combinations resulted in a polymorphism at the cDNA
      level. When used as hybridization probes, all of these cDNA fragments were single
      or low copy and all of them were polymorphic on Southern hybridizations using DNA
      from the isogenic lines. Genetic mapping revealed in each case at least one locus
      in the introgressed segment on chromosome 9 of tomato. Thus, this technique might
      provide a way for the direct isolation of transcribed sequences from specific
      regions of any animal or plant genome for which such lines exist.

PMID- 8552030
TI  - Recombination between heterologous linear and circular mitochondrial plasmids in
      the fungus Neurospora.
AB  - A strain of Neurospora intermedia from China contains five prominent extragenomic
      mitochondrial plasmids: three linear elements called zhisi plasmids, and two
      circular plasmids, Harbin-1 and -2. In one subculture, levels of four plasmids
      (all three zhisis and Harbin-1) fell to undetectable values and two novel linear
      plasmids appeared, Harbin-L and -L2, as well as a new small circular plasmid,
      Harbin-0.9. Cross-hybridization of restriction fragments and DNA sequencing
      showed that the Harbin-L plasmid was composed of parts of the circular Harbin-1
      plasmid and of one of the linear zhisi plasmids. A model is presented in which
      the Harbin-1 and zhisi plasmids are present within the same mitochondrion, and
      crossovers at two separate 7 bp sites of sequence identity effectively insert
      part of the circular Harbin-1 DNA into a zhisi linear plasmid, simultaneously
      deleting part of the zhisi element. The small plasmid Harbin-0.9 is a fragment of
      the Har-1 plasmid, and seems to be another product of the recombination process
      that created Har-L. Recombination of this type could have contributed to the wide
      array of mitochondrial plasmids found in natural populations of Neurospora.

PMID- 8552031
TI  - Marker rescue from the Nicotiana tabacum plastid genome using a
      plastid/Escherichia coli shuttle vector.
AB  - We recently reported an 868-bp plastid DNA minicircle, NICE1, that formed during
      transformation in a transplastomic Nicotiana tabacum line. Shuttle plasmids
      containing NICE1 sequences were maintained extrachromosomally in plastids and
      shown to undergo recombination with NICE1 sequences on the plastid genome. To
      prove the general utility of the shuttle plasmids, we tested whether plastid
      genes outside the NICE1 region could be rescued in Escherichia coli. The NICE1
      based rescue plasmid, pNICER1, carries NICE1 sequences for maintenance in
      plastids, the ColE1 ori for maintenance in E. coli and a spectinomycin resistance
      gene (aadA) for selection in both systems. In addition, pNICER1 carries a
      defective kanamycin resistance gene, kan*, to target the rescue of a functional
      kanamycin resistance gene, kan, from the recipient plastid genome. pNICER1 was
      introduced into plastids where recombination could occur between the homologous
      kan/kan* sequences, and subsequently rescued in E. coli to recover the products
      of recombination. Based on the expression of kanamycin resistance in E. coli and
      the analysis of three restriction fragment polymorphisms, recombinant kan genes
      were recovered at a high frequency. Efficient rescue of kan from the plastid
      genome in E. coli indicates that NICE1-based plasmids are suitable for rescuing
      mutations from any part of the plastid genome, expanding the repertoire of
      genetic tools available for plastid biology.

PMID- 8552032
TI  - Structural and functional analysis of the single-strand origin of replication
      from the lactococcal plasmid pWV01.
AB  - The single-strand origin (SSO) of the rolling-circle (RC), broad-host-range
      lactococcal plasmid pWVO1 was functionally characterized. The activity of this
      SSO in the conversion of single-stranded DNA to double-stranded DNA was tested
      both in vivo and in vitro. In addition, the effect of this SSO on plasmid
      maintenance was determined. The functional pWVO1 SSO comprises a 250 bp region,
      containing two inverted repeats (IRs). The activity of each IR was tested,
      separately and in combination, in a plasmid derivative that was otherwise
      completely devoid of structures that might function as SSO. One of the IRs (IR I)
      showed some homology with other previously described SSOs of the SSOA type, as
      well as with the conversion signal of the Escherichia coli phage phi X174. This
      IR was shown to have a partial, RNA polymerase-independent activity in
      complementary strand synthesis, both in vivo and in vitro. The second IR, which
      had no activity of its own, was required for full SSO activity, both in vivo and
      in vitro. The conversion of single-stranded DNA to the double-stranded form by
      the complete SSO was only partly sensitive to inhibition by rifampicin,
      indicating the existence of an RNA polymerase-independent pathway for this event.
      The results suggest that the pWVO1 SSO can be activated by two different routes:
      an RNA polymerase-dependent one (requiring the entire SSO), and an RNA polymerase
      independent one (requiring only IR I).

PMID- 8552033
TI  - Artificial antisense RNA regulation of YBR1012 (YBR136w), an essential gene from
      Saccharomyces cerevisiae which is important for progression through G1/S.
AB  - YBR1012 (YBR136w) is an essential gene from Saccharomyces cerevisiae identified
      during the systematic sequencing of part of the right arm of chromosome II. We
      previously constructed a conditional allele of YBR1012 based on antisense RNA, by
      inserting a small fragment of this gene downstream from the inducible UASGAL10
      CYC1 promoter. Several other antisense RNA constructions have since been made and
      their activity tested. The response of the system appears to be very delicate, as
      the presence or absence of 13 nucleotides of polylinker in the 300 nucleotide
      antisense transcript can dramatically modify its effectiveness. The most
      effective antisense RNA construction was used in flow cytometry studies to
      investigate the role of ybr1012p. The results show that during the antisense RNA
      block some 80% of the cells are arrested with their DNA unreplicated, suggesting
      that Ybr1012p is needed for progression through G1 or early S phase.

PMID- 8552034
TI  - A chlorophyll synthetase gene from Arabidopsis thaliana.
AB  - During the course of an Arabidopsis thaliana genome sequencing project, we
      identified a gene, G4, with a derived amino acid sequence showing homology to the
      product of the Rhodobacter capsulatus bchG locus which is involved in the
      esterification of bacteriochlorophyllide with geranylgeraniol. The relationship
      between this gene and bchG was confirmed by the isolation and analysis of a
      corresponding full-length cDNA. Comparison of genomic and cDNA sequences
      indicated that the gene is made up of 14 exons, some of them being very short.
      Southern and Northern analyses showed that this sequence represents a single-copy
      gene and its transcript is detected only in green or greening tissues. Both
      homologies and expression data suggest that this gene encodes a chlorophyll
      synthetase, one of the last enzymes of chlorophyll biosynthesis, and thus
      represents a new example of a nuclear gene encoding an enzyme of this pathway in
      higher plants.

PMID- 8552035
TI  - Combined mapping of AFLP and RFLP markers in barley.
AB  - AFLP marker technology allows efficient DNA fingerprinting and the analysis of
      large numbers of polymorphic restriction fragments on polyacrylamide gels. Using
      the doubled haploids from the F1 of the cross Proctor x Nudinka, 118 AFLP markers
      were mapped onto a barley (Hordeum vulgare L.) RFLP map, also including five
      microsatellite and four protein marker loci. The AFLP markers mapped to all parts
      of the barley chromosomes and filled in the gaps on barley chromosomes 2L, 4L and
      6 in which no RFLP loci had been mapped. Interestingly, the AFLP markers seldom
      interrupted RFLP clusters, but grouped next to them. The combined map covers 1873
      cM, with a total of 282 markers. The merging of AFLP and RFLP markers increased
      the total map length; 402 cM were added to the map at the tips of chromosomes or
      in regions corresponding to earlier gaps. Another 375 cM resulted from mapping
      AFLP markers near to RFLP clusters or in between non-clustered RFLP markers.

PMID- 8552036
TI  - A high-resolution map of the vicinity of the R1 locus on chromosome V of potato
      based on RFLP and AFLP markers.
AB  - The R1 allele confers on potato a race-specific resistance to Phytophthora
      infestans. The corresponding genetic locus maps on chromosome V in a region in
      which several other resistance genes are also located. As part of a strategy for
      cloning R1, a high-resolution genetic map was constructed for the segment of
      chromosome V that is bordered by the RFLP loci GP21 and GP179 and includes the R1
      locus. Bulked segregant analysis and markers based on amplified fragment length
      polymorphisms (AFLP markers) were used to select molecular markers closely linked
      to R1. Twenty-nine of approximately 3200 informative AFLP loci displayed linkage
      to the R1 locus. Based on the genotypic analysis of 461 gametes, eight loci
      mapped within the GP21-GP179 interval. Two of those could not be separated from
      R1 by recombination. For genotyping large numbers of plants with respect to the
      flanking markers GP21 and GP179 PCR based assays were also developed which
      allowed marker-assisted selection of plants with genotypes Rr and rr and of
      recombinant plants.

PMID- 8552037
TI  - The genomic instability of yeast cdc6-1/cdc6-1 mutants involves chromosome
      structure and recombination.
AB  - When diploid cells of Saccharomyces cerevisiae homozygous for the temperature
      sensitive cell division cycle mutation cdc6-1 are grown at a semipermissive
      temperature they exhibit elevated genomic instability, as indicated by enhanced
      mitotic gene conversion, mitotic intergenic recombination, chromosomal loss,
      chromosomal gain, and chromosomal rearrangements. Employing quantitative Southern
      analysis of chromosomes separated by transverse alternating field gel
      electrophoresis (TAFE), we have demonstrated that 2N-1 cells monosomic for
      chromosome VII, owing to the cdc6-1 defect, show slow growth and subsequently
      yield 2N variants that grow at a normal rate in association with restitution of
      disomy for chromosome VII. Analysis of TAFE gels also demonstrates that cdc6
      1/cdc6-1 diploids give rise to aberrant chromosomes of novel lengths. We propose
      an explanation for the genomic instability induced by the cdc6-1 mutation, which
      suggests that hyper-recombination, chromosomal loss, chromosomal gain and
      chromosomal rearrangements reflect aberrant mitotic division by cdc6-1/cdc6-1
      cells containing chromosomes that have not replicated fully.

PMID- 8552038
TI  - Marker enrichment and high-resolution map of the segment of potato chromosome VII
      harbouring the nematode resistance gene Gro1.
AB  - The dominant allele Gro1 confers on potato resistance to the root cyst nematode
      Globodera rostochiensis. The Gro1 locus has been mapped to chromosome VII on the
      genetic map of potato, using RFLP markers. This makes possible the cloning of
      Gro1 based on its map position. As part of this strategy we have constructed a
      high-resolution genetic map of the chromosome segment surrounding Gro1, based on
      RFLP, RAPD and AFLP markers. RAPD and AFLP markers closely linked to Gro1 were
      selected by bulked segregant analysis and mapped relative to the Gro1 locus in a
      segregating population of 1105 plants. Three RFLP and one RAPD marker were found
      to be inseparable from the Gro1 locus. Two AFLP markers were identified that
      flanked Gro1 at genetic distances of 0.6 cM and 0.8 cM, respectively. A genetic
      distance of 1 cM in the Gro1 region corresponds to a physical distance of ca. 100
      kb as estimated by long-range restriction analysis. Marker-assisted selection for
      nematode resistance was accomplished in the course of constructing the high
      resolution map. Plants carrying the resistance allele Gro1 could be distinguished
      from susceptible plants by marker assays based on the polymerase chain reaction
      (PCR).

PMID- 8552039
TI  - Analysis of splice donor and acceptor site function in a transposable gene trap
      derived from the maize element Activator.
AB  - Gene trap vectors have been used in insertional mutagenesis in animal systems to
      clone genes with interesting patterns of expression. These vectors are designed
      to allow the expression of a reporter gene when the vector inserts into a
      transcribed region. In this paper we examine alternative splicing events that
      result in the expression of a GUS reporter gene carried on a Ds element which has
      been designed as a gene trap vector for plants. We have developed a rapid and
      reliable method based on PCR to study such events. Many splice donor sites were
      observed in the 3' Ac border. The relative frequency of utilisation of certain
      splice donor and acceptor sites differed between tobacco and Arabidopsis. A
      higher stringency of splicing was observed in Arabidopsis.

PMID- 8552040
TI  - Novel GUS expression patterns following transposition of an enhancer trap Ds
      element in Arabidopsis.
AB  - Enhancer trap derivatives of the maize Dissociation (Ds) transposon were
      introduced into Arabidopsis thaliana. The enhancer trap Ds was so designed that
      upon transposition to sites containing regulatory sequences in adjacent genomic
      DNA, transcription of a Ds-borne beta-glucuronidase (GUS) gene would be
      activated. Sixty percent of all transposition events were associated with GUS
      expression patterns including one linked to a mutant phenotype. Patterns of GUS
      expression were found in various organs and were stably inheritable in the F4 and
      F5 progenies. These results demonstrate the potential value of the technique as a
      means for detection of developmentally regulated genes and analysis of their
      function. The enhancer trap construct used in our experiments, as well as the
      seeds of primary transformants are publicly available.

PMID- 8552041
TI  - Modulation of bleomycin-induced mitotic recombination in yeast by the aminothiols
      cysteamine and WR-1065.
AB  - The cancer chemotherapy drug bleomycin (BLM) is a potent inducer of genetic
      damage in a wide variety of assays. The radioprotectors cysteamine (CSM) and WR
      1065 have been shown in previous studies to potentiate the induction of
      micronuclei and chromosome aberrations by BLM in Go human lymphocytes. By
      contrast, WR-1065 is reported to reduce the induction of hprt mutations by BLM in
      Chinese hamster cells. To elucidate the basis for these interactions, we examined
      the effects of CSM and WR-1065 on the induction of mitotic gene conversion by BLM
      in the yeast Saccharomyces cerevisiae. Treatment with BLM causes a dose-dependent
      increase in the frequency of mitotic gene conversion and gene mutations. Unlike
      its potentiation of BLM in Go lymphocytes, WR-1065 protected against the
      recombinagenicity of BLM in yeast. CSM was also strongly-antirecombinagenic
      under, some conditions, but the nature of the interaction depended strongly on
      the treatment conditions. Under hypoxic conditions, cysteamine protected against
      BLM, but under oxygen-rich conditions CSM potentiated the genetic activity of
      BLM. The protective effect of aminothiols against BLM may be ascribed to the
      depletion of oxygen required for the activation of BLM and the processing of BLM
      induced damage. Aminothiols may potentiate the effect of BLM by acting as an
      electron source for the activation of BLM and/or by causing conformational
      alterations that make DNA more accessible to BLM. The results indicate that
      aminothiols have a strong modulating influence on the genotoxicity of BLM in
      yeast as they do in other genetic assays. Moreover, the modulation differs
      markedly depending on physiological conditions. Thus, yeast assays help to
      explain why aminothiols have been observed to potentiate BLM in some genetic
      systems and to protect against it in others.

PMID- 8552042
TI  - Gene silencing in transgenic tobacco hybrids: frequency of the event and
      visualization of somatic inactivation pattern.
AB  - We have investigated the stability of the expression of different T-DNA-borne
      genes in hybrid tobacco lines. These lines were constructed to rescue rolC
      induced male sterility in kanamycin-resistant P35s-rolC transgenic tobacco plants
      by expression of rolC antisense genes. Using five different tester lines, a total
      of 158 hybrids was obtained. We observed inactivation of transgene expression in
      20% of the F1 progeny and in 35% of the backcrossed F2 progeny, as indicated by
      the loss of kanamycin resistance. In 3% of all crosses complete loss of
      antibiotic resistance was noted, while in most affected hybrid progeny only part
      of the population became kanamycin sensitive. Single genes could be selectively
      inactivated on T-DNAs harboring several genes. Gene inactivation was not
      restricted to one of the two T-DNAs examined. Somatic silencing, visualized by a
      cell-specific 35SGUSINT marker gene, occurred in a random fashion or exhibited an
      inherited specific pattern. The type of somatic silencing pattern observed
      indicated developmental control of the process. Two phenotypic classes could be
      distinguished with respect to frequency and timing of the inactivation process.
      Rapid gene inactivation, occurring within a few weeks after germination of hybrid
      seedlings, was characterized by complete methylation of restriction sites in the
      promoter of the silenced gene, resetting of gene expression during meiosis,
      heredity of the developmentally controlled program of gene silencing in
      subsequent generations, and rapid reactivation of gene expression after genetic
      separation of the different T-DNAs. In contrast, a slow type of gene inactivation
      was of a more stochastic nature and was recognized only in hybrids of the
      backcrossed F2 generation. In this case the degree of promoter methylation, which
      could extend beyond the T-DNA borders, was not correlated with the reduction in
      steady-state poly(A)+ mRNA levels, the silenced state was transmitted through
      meiosis and reactivation lasted several generations. The implications of the
      observations for our understanding of the gene inactivation process are
      discussed.

PMID- 8552043
TI  - Fission yeast sta mutations that stabilize an unstable minichromosome are novel
      cdc2-interacting suppressors and are involved in regulation of spindle dynamics.
AB  - Cytological observations have shown that the presence of unstable minichromosomes
      can delay progression through the early stages of mitosis in fission yeast
      (Schizosaccharomyces pombe), suggesting that such minichromosomes may provide a
      useful tool for examining the system that regulates the coordinated segregation
      of chromosomes. One such unstable minichromosome is a large circular
      minichromosome. We previously showed that the mitotic instability of this
      minichromosome is probably due to the frequent occurrence of catenated forms of
      DNA after replication. To identify genes involved in the regulation of chromosome
      behavior in mitosis, we isolated mutants which stabilized this minichromosome.
      Three loci (sta1, sta2, and sta3) were identified. Two of them were found to be
      suppressors of temperature-sensitive mutations in cdc2, which encodes the
      catalytic subunit of muturation promoting factor (MPF). They show no linkage to,
      and are thus different from, suc1, and cdc13, previously identified as genes that
      interact with cdc2. The other mutation mapped to a gene previously identified as
      being required for the correct formation of the mitotic spindle. Data provided in
      this study suggest that the sta genes are involved in the regulation of spindle
      dynamics to ensure proper chromosome segregation during mitosis.

PMID- 8552044
TI  - Insertion of a novel transposable element in the tyrosinase gene is responsible
      for an albino mutation in the medaka fish, Oryzias latipes.
AB  - In the medaka fish (Oryzias latipes) many mutants for body color have been
      isolated. A typical example is the recessive oculocutaneous albino mutant i,
      which has amelanotic skin and red-colored eyes with no tyrosinase activity. To
      cast light on the molecular basis of the albino mechanism, we performed Southern
      blot analysis of genomic DNA from the mutant with an authentic tyrosinase gene
      probe; the results demonstrate that an extra 1.9 kb fragment is present inside
      the first exon. The insertion is responsible for the oculocutaneous albinism.
      About 80 copies of this fragment are present in the genomes of albino-i and wild
      type fish; these repeated sequences are here designated Tol1 elements and the
      particular element found in the tyrosinase gene of albino-i is denoted Tol1-tyr.
      The nucleotide sequence of Tol1-tyr shows that the fragment (i) carries terminal
      inverted repeats of 14 bp, and (ii) is flanked by duplicated 8 bp segments of the
      host chromosome. These are properties of DNA-mediated transposable elements.
      Comparison of the nucleotide sequence of Tol1-tyr with other sequences in DNA
      databases, with special attention to sequences of transposable elements known to
      date, did not reveal any similarity. Thus, Tol1 constitutes a hitherto unknown
      family of DNA transposable elements.

PMID- 8552045
TI  - Structure and distribution of specific cis-elements for transcriptional
      regulation of PHO84 in Saccharomyces cerevisiae.
AB  - Transcription of the PHO84 gene encoding a Pi transporter in Saccharomyces
      cerevisiae is regulated by the Pi concentration in the medium. The promoter
      region of PHO84 bears five copies of the motif 5'-CACGT(G/T)-3', a candidate for
      the upstream activation site (UAS) that binds the transcriptional activator
      protein of the phosphatase regulon, Pho4p. These motifs are found at nucleotides 
      880 (site A), -587 (B), -436 (C), -414 (D), and -262 (E) relative to the putative
      ATG codon of PHO84. The Pho4p binds to all five 6-bp motifs with various
      affinities. Deletion analysis of the PHO84 promoter using a PHO84-lacZ fusion
      gene and base substitutions in the 6-bp motif revealed that two copies of the 6
      bp motif, either C or D, and E, are necessary and sufficient for full regulation
      of the PHO84 gene. Results of expression studies with a CYC1-lacZ fusion gene
      with various 36-bp oligonucleotides including the 30-bp sequences around site D
      or E, or with modified sequences, inserted in the CYC1 promoter region indicated
      that the 6-bps motif flanked by a thymine nucleotide at its 5' end is much less
      effective as a UAS site for Pho4p in vivo than other versions. Thus, the
      consensus sequences for phosphatase regulation are 5'-GCACGTGGG-3' and 5'
      GCACGTTTT-3' which differ from the binding sequences for the Cpflp protein
      required for transcription of the genes in methionine biosynthesis and for
      centromere function. However, Pho4p binding in vitro was unaffected by
      modification of the 5' or 3' flanking sites of the 6-bp motif, while modification
      inside the 6-bp motif affected it severely. The UAS function of the GCACGTTTT
      motif with respect to the Pi signal depends on its orientation in the promoter
      sequence.

PMID- 8552046
TI  - Molecular dissection of the flagellum-specific anti-sigma factor, FlgM, of
      Salmonella typhimurium.
AB  - In the flagellar regulon of Salmonella typhimurium, the flagellar operons are
      divided into three classes, 1, 2 and 3, with respect to transcriptional
      hierarchy. Class 3 operons are controlled positively by FliA, a flagellum
      specific sigma factor, and negatively by FlgM, an anti-sigma factor which binds
      to FliA and inhibits its activity. The sequential expression of flagellar operons
      is coupled to the assembly process of flagellar structures. This coupling is
      achieved by the fact that FlgM is exported out of the cell through the flagellar
      structures that are formed by the functions of the class 1 and 2 genes.
      Therefore, FlgM has a dual function: it can bind to FliA and is capable of being
      exported through the flagellar structure. In this study, using a set of deletion
      mutants of flgM in high-expression plasmids, we demonstrated that polypeptides
      containing the C-terminal portion of FlgM could inhibit the FliA-dependent
      transcription of the class 3 genes. Loss of amino acids near the N-terminus
      eliminated the export of the protein, while loss of C-terminal amino acids did
      not affect this function. These results indicate that the domain essential for
      export lies in the N-terminal region and that for FliA-binding in the C-terminal
      region.

PMID- 8552047
TI  - Mapping of linear epitopes recognized by monoclonal antibodies with gene-fragment
      phage display libraries.
AB  - Epitope mapping with mono- or polyclonal antibodies has so far been done either
      by dissecting the antigens into overlapping polypeptides in the form of
      recombinantly expressed fusion proteins, or by synthesizing overlapping short
      peptides, or by a combination of both methods. Here, we report an alternative
      method which involves the generation of random gene fragments of approximately 50
      200 bp in length and cloning these into the 5' terminus of the protein III gene
      of fd phages. Selection for phages that bind a given monoclonal antibody and
      sequencing the DNA inserts of immunopositive phages yields derived amino acid
      sequences containing the desired epitope. A monoclonal antibody (mAb 215)
      directed against the largest subunit of Drosophila RNA polymerase II (RPB215) was
      used to map the corresponding epitope in a fUSE5 phage display library made of
      random DNA fragments from plasmid DNA containing the entire gene. After a single
      round of panning with this phage library, bacterial colonies were obtained which
      produced fd phages displaying the mAb 215 epitope. Sequencing of single-stranded
      phage DNA from a number of positive colonies (recognized by the antibody on
      colony immunoblots) resulted in overlapping sequences all containing the 15mer
      epitope determined by mapping with synthetic peptides. Similarly, we have
      localized the epitopes recognized by a mouse monoclonal antibody directed against
      the human p53 protein, and by a mouse monoclonal antibody directed against the
      human cytokeratin 19 protein. Identification of positive colonies after the
      panning procedure depends on the detection system used (colony immunoblot or
      ELISA) and there appear to be some restrictions to the use of linker-encoded
      amino acids for optimal presentation of epitopes. A comparison with epitope
      mapping by synthetic peptides shows that the phage display method allows one to
      map linear epitopes down to a size only slightly larger than the true epitope. In
      general, our phage display method is faster, easier, and cheaper than the
      construction of overlapping fusion proteins or the use of synthetic peptides,
      especially in cases where the antigen is a large polypeptide such as the 215 kDa
      subunit of eukaryotic RNA polymerase II.

PMID- 8552048
TI  - The isolation of Ant1, a transposable element from Aspergillus niger.
AB  - A transposable element has been isolated from the industrially important fungus
      Aspergillus niger (strain N402). The element was identified as an insertion
      sequence within the coding region of the nitrate reductase gene. It had inserted
      at a TA site and appeared to have duplicated the target site upon insertion. The
      isolated element was found to be 4798 bp in length and contained 37-bp inverted,
      imperfect, terminal repeats (ITRs). The sequence of the central region of the
      element revealed an open reading frame (designated ORF1) which showed similarity,
      at the amino acid level, to the transposase of the Tc1/mariner class of DNA
      transposons. Another sequence within the central region of the element showed
      similarity to the 3' coding and downstream untranslated region of the amyA gene
      of A. niger. Sequence homology and structural features indicate that this
      element, which has been named Ant1 (A. niger transposon 1), is related to the
      Tc1/mariner group of DNA transposons. Ant1 is apparently present as a single copy
      in strain N402 of A. niger.

PMID- 8552049
TI  - Identification and expression of the Neurospora crassa mei-3 gene which encodes a
      protein homologous to Rad51 of Saccharomyces cerevisiae.
AB  - The mei-3 gene of Neurospora crassa encodes a homolog of the Escherichia coli
      RecA and Saccharomyces cerevisiae Rad51 proteins, which are required for
      recombination and repair of DNA double-strand breaks. To determine the molecular
      function of MEI3 protein, anti-MEI3 antibody was prepared and used in Western
      blot analysis. The antibody cross-reacted only with crude extracts prepared from
      perithecia, the fruiting bodies of Neurospora. The molecular weight of the MEI3
      protein was estimated to be 38 kDa. Transformation experiments showed that a DNA
      fragment longer than previously reported was needed to complement the mei-3
      mutation. On sequencing cDNA and genomic DNA, one open reading frame (ORF) was
      found, which consists of three exons interrupted by two small introns. This ORF
      encoded a MEI3 protein of 353 amino acids, and the inferred MW of 38 kDa is in
      good agreement with the results from Western blot analysis. Comparisons of MEI3
      with other Rad51 homologs indicated that MEI3 protein contains the two conserved
      core domains (I and II) generally observed in Rad51 homologs in eukaryotes.
      Northern blot analysis showed that expression of mei-3 was raised remarkably
      after UV-irradiation or methyl methanesulfonate (MMS)-treatment. The transcript
      size was 1.6 kb and this was also larger than was reported previously.

PMID- 8552050
TI  - Identification of a centromeric activity in the autonomously replicating TRA
      region allows improvement of the host-vector system for Candida maltosa.
AB  - A centromeric activity was identified in the previously isolated 3.8 kb DNA
      fragment that carries an autonomously replicating sequence (ARS) from the yeast
      Candida maltosa. Plasmids bearing duplicated copies of the centromeric DNA
      (dicentric plasmids) were physically unstable and structural rearrangements of
      the dicentric plasmids occurred frequently in the transformed cells. The
      centromeric DNA activity was dissociated from the ARS, which is 0.2 kb in size,
      and was delimited to a fragment at least 325 bp in length. The centromeric DNA
      region included the consensus sequences of CDEI (centromeric DNA element I) and
      an AT-rich CDEII-like region of Saccharomyces cerevisiae but had no homology to
      the functionally critical CDEIII consensus. A plasmid bearing the whole 3.8 kb
      fragment was present in 1-2 copies per cell and was maintained stably even under
      non-selective culture conditions, while a plasmid having only the 0.2 kb ARS was
      unstable and accumulated to high copy numbers. The high-copy-number plasmid
      allowed us to overexpress a gene to a high level, which had never been attained
      before, under the control of both constitutive and inducible promoters in C.
      maltosa.

PMID- 8552052
TI  - [The Russian human genome program].

PMID- 8552051
TI  - Functional analysis by site-directed mutagenesis of individual amino acid
      residues in the flavin domain of Neurospora crassa nitrate reductase.
AB  - Nitrate reductase of Neurospora crassa is a complex multi-redox protein composed
      of two identical subunits, each of which contains three distinct domains, an
      amino-terminal domain that contains a molybdopterin cofactor, a central heme
      containing domain, and a carboxy-terminal domain which binds a flavin and a
      pyridine nucleotide cofactor. The flavin domain of nitrate reductase appears to
      have structural and functional similarity to ferredoxin NADPH reductase (FNR).
      Using the crystal structure of FNR and amino acid identities in numerous nitrate
      reductases as guides, site-directed mutagenesis was used to replace specific
      amino acids suspected to be involved in the binding of the flavin or pyridine
      nucleotide cofactors and thus important for the catalytic function of the flavin
      domain. Each mutant flavin domain protein was expressed in Escherichia coli and
      analyzed for NADPH: ferricyanide reductase activity. The effect of each amino
      acid substitution upon the activity of the complete nitrate reductase reaction
      was also examined by transforming each manipulated gene into a nit-3- null mutant
      of N. crassa. Our results identify amino acid residues which are critical for
      function of the flavin domain of nitrate reductase and appear to be important for
      the binding of the flavin or the pyridine nucleotide cofactors.

PMID- 8552053
TI  - [An excess of eukaryotic genes is lessened as a result of splicing].
AB  - Statistical features of nucleotide sequences are analyzed for the redundancy of
      their sites, introns vs. exons. In human genes with known exon-intron structure,
      the introns were found to be more redundant than the exons. The redundancy was
      defined as the minimal length of a nucleotide sequence not repeated within a
      gene. Mechanisms alternating exon-intron statistical pattern are discussed.

PMID- 8552054
TI  - [Cloning and expression of the Bacillus stearothermophilus neutral proteinase
      gene in Bacillus subtilis cells].
AB  - Gene of thermostable Bacillus stearothermophilus metalloprotease was cloned and
      expressed in mesophilic Bacillus subtilis cells. It was demonstrated that this
      gene is closely related by its restriction map to B. stearothermophilus T
      metalloprotease gene cloned earlier. Thermostability level and thermal optimum of
      activity of metalloprotease, the product of cloned gene expression, were
      estimated.

PMID- 8552055
TI  - [Features of the primary structure of DNA from the synaptonemal complex of the
      golden hamster].
AB  - DNA of golden hamster synaptonemal complex (SC) was cloned and partially
      sequenced. Computer analysis was performed to compare the SC DNA sequences for
      different families of eukaryotic genomic DNA. SC DNA is homologous to LINE family
      and in contrast to genomic DNA is enriched with alternative (GT/CA)n sequences
      and palindromes. By its ability to form potential hairpin loops, SC DNA is
      similar to nuclear matrix-associated regions of DNA (MARs) and differs
      considerably from DNA of microsatellite loci. It is noteworthy that SC DNA, which
      is supposed to be involved in meiotic recombination, and DNA of immunoglobulin
      genes, involved in somatic recombination, are both enriched with palindromes. The
      discovered peculiarities of the structure of hamster SC DNA allow us to join it
      with rat SC DNA into a special family of rodent genomic DNA sequences.

PMID- 8552056
TI  - [Conserved regions of potential ORF1 protein products of mobile elements and
      retroviral proteins, encoded by the gag gene].
AB  - Computer search for homology regions of retroelement ORF1 protein products and
      retroviral gag-encoded proteins was performed using nucleotide and protein
      sequences of 113 retrotransposons, conservative domains were found in amino acid
      sequences encoded by viral gene gag: 22 and 17 amino acid residues in capsid and
      nucleocapsid proteins, respectively. Similar regions were found in potential
      protein products of ORF1. Another conservative region was revealed by multiple
      alignment in amino acid sequences of potential protein products of ORF1 of mobile
      elements and in p19 matrix protein of some retroviruses; this region is different
      in mobile elements from different classes, but within each class it shows high
      similarity. The secondary structure of this region is an alpha-helix.

PMID- 8552057
TI  - [Detection and analysis of Tetrahymena pyriformis 26S ribosomal DNA domain
      sequences, differing in degree of evolutionary conservation].
AB  - Domains of different evolutionary conservatism were defined in the 26S rDNA
      sequence of T. pyriformis. The fragment of studied DNA (1212 bp) showing high
      evolutionary conservatism was cloned. It was shown this fragment of DNA may be
      used to a probe for blot-hybridization analysis of the structure of rDNA from
      various taxa, protists to mammals. Superconservative and hypervariable domains
      were defined. The first are good for the primers for PCR analysis of rDNA from
      various taxa, the second--for species specific primers.

PMID- 8552058
TI  - [Modification of DNA with 4-aminooxybutylamine as a method for obtaining highly
      sensitive hybridization probes. Mapping of the gene for human chorionic
      somatomammotropin hormone].
AB  - A new method for preparation of highly sensitive nonradioactive probes for dot,
      dot-blot and in situ hybridization was developed. The method is based on chemical
      modification (transamination) of cytosine residues with 4-aminooxybutylamine
      following by coupling biotin or fluorescein to aliphatic aminogroups introduced
      into DNA. Such a probe have been used for detection of gene encoding chorionic
      somatomammotropin hormone (hCS) in genomic blot hybridization. The gene hCS was
      mapped using isotopic and nonisotopic in situ hybridization on human chromosome
      17.

PMID- 8552059
TI  - [Organization of ribosomal DNA from the phytoflagellates Astasia longa and
      Euglena gracilis: comparison of the structure of 19S and 28S rRNA genes].
AB  - Restriction maps of Astasia longa and Euglena gracilis var. bacillaris were built
      and localization of 5.8S, 19S and 28S rRNA genes was established on them by blot
      hybridization method. In the A. longa and E. gracilis plasmid rDNA three
      intergeneous regions were found, two of which were intergeneous transcribed
      spacers flanking 5.8S RNA gene, and the third region seems to be an untranscribed
      spacer. Localization of 9 primers from E. gracilis was established on A. longa
      19S rRNA gene by PCR; it was similar to E. gracilis. Using amplified A. longa 19S
      rRNA gene (2300 bp) we have determined the sequence of its 3'-region, which
      showed 87% homology with the same region of E. gracilis. Using plasmid pA1 S3-H1
      containing S3-H1 fragment of A. longa rDNA the sequence of 28S rRNA gene 3'
      region was determined. This sequence includes regions homologous to corresponding
      regions of E. gracilis Z: 6 nucleotides of 12/13 internal spacer, complete 13/14
      internal spacer (86 bp), genes for 13th and 14th 28S rRNA components (56 and 86
      bp) with approximately 90% of homology with E. gracilis Z, and fragment of
      untranscribed spacer (136 bp) with approximately 70% homology. It was shown that
      28S rRNA genes of A. longa and E. gracilis have similar structure. Our data allow
      to conclude that these phytoflagellats are closely related.

PMID- 8552060
TI  - [Molecular phylogeny of Turbellaria, based on data from comparing the nucleotide
      sequences of 18S ribosomal RNA genes].
AB  - Polymerase chain reaction and direct sequencing of the 5'-end region of the 18S
      ribosomal RNA gene were used to infer phylogenetic relationship among
      turbellarian flatworms from Lake Baikal. Representatives of 5 orders (Tricladida-
      10 spp., Lecithoepitheliata--5 spp., Prolecithophora--3 spp., Proseriata and
      Kalyptorhynchia one for each) were studied; nucleotide sequence of more than 340
      nucleotides was determined for each species. Consensus sequence for each order
      having more than one representative species was determined. Distance matrix and
      maximum parsimony approaches were applied to infer phylogenies. Bootstrap
      procedure was used to estimate confidence limits, at the 100% level by
      bootstrapping, the group of three orders: Kalyptorhynchia, Proseriata and
      Lecithoepitheliata was found to be monophyletic. However, subsets inside the
      group had no significant support to be preferred or rejected. Our data do not
      support traditional systematics which joins two suborders Tricladida and
      Proseriata into the single order Seriata, and also do not support comparative
      anatomical data which show close relationship of Lecithoepitheliata and lower
      Prolecithophora.

PMID- 8552061
TI  - [Interaction of DNA with calcium ions by a vibrational spectroscopy].
AB  - DNA complexes with Ca2+ ions formed in films at various relative humidities were
      studied by IR-spectroscopy for molar concentration ratio of calcium ions and DNA
      phosphate groups [Ca2+]/[P] = 0.4-20. It is shown that the transition of DNA
      complexed with Ca2+ ions into B-form occurs at higher average numbers (n) of
      water molecules absorbed per nucleotide: n > 18 at the ratio [Ca2+]/[P] = 10, n >
      24 at [Ca2+]/[P] = 20 and n > 12 in the absence of Ca2+ ions. This shows stronger
      binding of water molecules in the hydrate shell of DNA-Ca2+ if compared with free
      DNA. The results confirm a model proposed earlier. Ca2+ ions interact with
      phosphate oxygens of DNA and with N(7) nitrogens of guanine forming chelated
      complexes.

PMID- 8552062
TI  - [Interaction of DNA molecules with divalent platinum coordination complexes. II.
      Effect of the nature and location of ligands in the first platinum coordination
      sphere].
AB  - The interaction of DNA molecule with some coordination compounds of the divalent
      platinum: cis-DDP, trans-DDP, [(NH3)4Pt]Cl2 and K2PtCl4 was studied. It was shown
      that the transition of the cis-DDP, trans-DDP, and [PtCl4]2- to aquo-complexes is
      necessary for their binding with DNA in solution. It was shown that the labile
      chloride groups are responsible for the formation of the energetically strong
      binding. The distance between chloride groups in cis-DDP is optimal for
      incorporation of two groups of DNA bases into the first coordination sphere of
      platinum. The complexes are also stabilized with phosphate in the external
      coordination sphere of platinum. The sterical non-conformity between the DNA
      structure and positions of chloride groups and the orientation of the amino
      groups in trans-DDP are the main obstructions for the formation of bidentate DNA
      trans-DDP complexes. The existence of more than two vacant positions for binding
      with DNA in [PtCl4]2- does not stabilise the complex. The compound [(NH3)4Pt]Cl2
      cannot produce coordination bonds with DNA, because its first coordination sphere
      is completed with amino groups; it interacts with DNA, forming principally
      different complexes.

PMID- 8552063
TI  - [The effect of phalloidin on stability of F- and G-actin].
AB  - Intrinsic tryptophan fluorescence and fluorescence of a hydrophobic probe bis-ANS
      were used to study the effect of phalloidin, a bicyclic heptapeptide toxin, on
      stability of monomeric (G) and polymeric (F) actin. It was found that bis-ANS
      fluorescence is sensitive to the actin polymerization process. Phalloidin in
      concentrations from 1 to 2 molecules per 1 actin molecule shifts the thermally
      induced unfolding transition in F-actin toward about 15 degrees C higher
      temperatures. The stabilizing effect of phalloidin is even more evident in the
      case of urea denaturation of F-actin. Moreover, phalloidin stabilizes against
      denaturing by not only F-actin, but G-actin as well, showing direct stabilizing
      interactions between phalloidin and G-actin.

PMID- 8552064
TI  - [Structure-activity relationships in multienzyme complexes].
AB  - Structures and molecular kinetic models of function of 2-oxo acid dehydrogenase
      complexes were analyzed. It was suggested that identical protein subunits in the
      multienzyme complexes as in the structure capable of self-assembly have identical
      contacts with the neighbors and identical environment. By sharing the enzyme
      aggregate subunits into distinct conformational classes the peripheral components
      were demonstrated to be arranged on the core so that the entire complex would
      have a definite symmetry. The number of the conformational classes is specified
      by the architecture of the core and considerations of symmetry. The results have
      allowed us to consider the mechanisms of functioning of the complexes. Specific
      examples are discussed.

PMID- 8552065
TI  - [Functional activity of T-, B-lymphocytes, and macrophages during suppression of
      expression of the env gene from an endogenous retrovirus genome].
AB  - Incubation of murine spleen cells with antisense oligonucleotide complementary to
      initiation site of this gene highly increased RNA synthesis relative to the
      normal T- and B-lymphocytes from spleen. In macrophages, inhibition of gene env
      expression stimulated phagocytosis and IL-1 production. Under these conditions,
      the level of expression of proviral envelope transmembrane p15E protein, which in
      infectious type C retroviruses is known to be immunosuppressive, decreased in
      spleen cells. Antisense oligonucleotide stimulatory effect on murine spleen cell
      RNA synthesis is presumably related to the reduced production of endogenous p15E.

PMID- 8552066
TI  - [Study of plant lectins from Viscum album using monoclonal antibodies].
AB  - Monoclonal antibodies (monAT) against both native (TA5, TB12) and denatured
      (TB33, TB35) plant toxin ML1 from Viscum album have been obtained. The
      interaction of monAT against native toxin with its isoforms ML2 and ML3 was
      investigated. It was shown that monAT TA5 to A-chain of ML1 toxin cross-reacted
      with ML2 and ML3 isoforms. TA5 did not inhibit enzyme activity of A-chain in cell
      free rabbit reticulocyte system. It was shown that monAT TB12 reacted with
      galactose-binding site of B-subunit. Both monAT had no cross-reactions with plant
      toxin ricin. The binding constants for TA5 with ML1, ML2, ML3 respectively were
      4.3.10(7) M-1, 1.2.10(7) M-1, and 0.3.10(7) M-1. The binding constants for TB12
      were 2.10(7) M-1 with ML1 toxin, and more than 10(6) M-1 with ML2 and ML3. The
      nature of heterogeneity in ML toxin family is discussed. Test-systems for ML1
      determination in different V. album extracts are suggested.

PMID- 8552067
TI  - [Surface localization of amino acids in influenza virus hemagglutinin during
      functional transformation of virions by acidic pH].
AB  - Tritium planigraphy method was used to study the surface amino acids in influenza
      virus hemagglutinin (HA) at the functional transformation of virions by acidic
      pH. Influenza viruses undergo this transformation when virions penetrate a target
      cell. The mild bombardment of a whole virion by hot tritium atoms labels the
      surface-exposed HA amino acids without disturbing virion structure and
      infectivity. A comparison of the values of specific radioactivity of the HA
      subunits (HA1 and HA2) and analysis of the label distribution in individual amino
      acids in control (pH 7.4) and experimental (pH 5.0) viral samples has shown that:
      (i) The accessibility of a hemagglutinin molecule for tritium labeling is
      decreased at acidic pH; (ii) Compactization of apical HA1 hemagglutinin subunit
      increases at acidic pH; (iii) The HA1 compactization increases the exposition of
      the basal HA2 hemagglutinin subunit; (iv) The fusion peptide of the HA2 subunit
      (the N-terminal part) is not accessible for tritium label after the acidic
      exposition of virions. These data are in an agreement with the hypothesis that
      hemagglutinin fusion peptide is exposed only while contacting the target cell
      membrane at acidic pH.

PMID- 8552068
TI  - [Analysis and interaction of myosin active centers during a mechanochemical
      cycle].
AB  - A model of myosin complex with two active sites is considered. Each of the sites
      is supposed to pass through four states during a cycle of ATP hydrolysis. The
      model describes the distribution of the complex between states and the ATP
      hydrolysis rate as dependent on ATP concentration and reaction constants. Some of
      the constants were determined experimentally [6], but these values reproduce
      experimental curves [5] only with the assumption of cooperativity. If the first
      site is bind to actin, the rate of binding for the second one is shown to
      increase tenfold. If one of the sites is bind to actin by a "pulling" bridge, and
      the second site is in "rigor" state, then the ATP binding for the second site is
      about ten times faster. The transition into the rigor state proceeds much faster
      if both sites form pulling bridges. The rate of binding to actin is the same for
      one and for two sites.

PMID- 8552069
TI  - [Internal initiation of translation in eukaryotes. Chemical probing of the
      encephalomyocarditis virus RNA IRES-element in the 48S preinitiation complex].
AB  - Using in vitro T7 polymerase system, the transcript containing the IRES-element
      (nts 315-833), and the initial part of the coding sequence of
      encephalomyocarditis virus (EMCV) RNA (nts 834-1155) was prepared. Its complex
      with the 40S ribosomal subunit (48S preinitiation complex) was then isolated by
      sucrose gradient sedimentation from ascites carcinoma Krebs2 cell extracts after
      preincubation with the transcript. The complex was treated with dimethylsulphate
      (DMS), a common reagent for chemical probing of A and C residues in single
      stranded RNA regions. The modified nucleotides were identified by primer
      extension inhibition analysis in reverse transcription reaction. The pattern of
      modification of the 48S complex was compared with that for the corresponding free
      mRNP. Multiple protection of A residues against DMS modification was found in the
      domains of the IRES-element proximal to the initiation AUG codon (nt 834-836).
      The mechanism of internal translational initiation of EMCV RNA and other
      picornaviral RNAs is discussed.

PMID- 8552070
TI  - [New nucleotide inhibitors of human DNA polymerase alpha].
AB  - 2'-Deoxythymidine 5'-triphosphate and 2'-deoxyadenosine 5'-triphosphate analogs
      containing a methylene group between the alpha phosphorus and 5' oxygen were
      synthesized. The substrate properties of these compounds toward some mammalian
      DNA polymerases and retroviral reverse transcriptases were evaluated using a
      system containing phage M13mp10 DNA, a synthetic oligonucleotide, and the enzyme.
      The compounds containing a hydroxyl at the 3' position were incorporated into the
      DNA chain by DNA polymerase alpha and terminal deoxynucleotidyl transferase, but
      were not recognized by retroviral reverse transcriptases and mammalian DNA
      polymerases epsilon and beta. The selectivity of the compounds synthesized was
      capitalized on during simultaneous isolation of DNA polymerases alpha and epsilon
      from human placenta. A methylene group was also introduced into the acyclovir
      molecule. It was shown that this modification inactivates furanose-related
      nucleotide analogs, but has a minor effect on the substrate properties of acyclic
      nucleotide analogs.

PMID- 8552071
TI  - Tumor necrosis factor alpha gene regulation in activated T cells involves ATF
      2/Jun and NFATp.
AB  - The human tumor necrosis factor alpha (TNF-alpha) gene is one of the earliest
      genes expressed upon the activation of a T or B cell through its antigen
      receptor. Previous experiments have demonstrated that in stimulated T cells, a
      TNF-alpha promoter element, kappa 3, which binds NFATp, is required for the
      cyclosporin A-sensitive transcriptional activation of the gene. Here, we
      demonstrate that a cyclic AMP response element (CRE), which lies immediately
      upstream of the kappa 3 site, is also required for induction of TNF-alpha gene
      transcription in T cells stimulated by calcium ionophore or T-cell receptor
      ligands. The CRE binds ATF-2 and Jun proteins in association with NFATp bound to
      kappa 3. These proteins bind noncooperatively in vitro; however, the
      transcriptional activity of the CRE/kappa 3 composite site is dramatically higher
      than the activity of the kappa 3 site alone, indicating that the two sites
      cooperate in vivo. This study is the first demonstration of a role for ATF-2 in
      TNF-alpha gene transcription and of a functional interaction between ATF-2/Jun
      and NFATp. This novel pairing of NFATp with ATF-2/Jun may account for the
      specific and immediate pattern of TNF-alpha gene transcription in stimulated T
      cells.

PMID- 8552072
TI  - Repression of beta interferon gene expression in virus-infected cells is
      correlated with a poly(A) tail elongation.
AB  - Expression of beta interferon (IFN-beta) is transiently induced when Namalwa B
      cells (Burkitt lymphoma cell line) are infected by Sendai virus. In this study,
      we found that an elongation of the IFN-beta mRNA could be detected in virus
      infected cells and that such a modification was not observed when the IFN-beta
      transcript was induced by a nonviral agent, poly(I-C). Treatment of the cells
      with a transcriptional inhibitor (actinomycin D or 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole) resulted in further elongation of the transcript.
      Characterization of the elongated IFN-beta transcript by primer extension and
      RNase H treatment showed that the modification was a result of an elongated
      poly(A) tail of up to 400 nucleotides. We conclude that the poly(A) tail
      elongation of the IFN-beta transcript is associated with the viral infection.
      Furthermore, the presence of the elongated IFN-beta transcript correlated with a
      decrease of IFN-beta protein in the medium and in cell extracts. Sucrose gradient
      analysis of cytoplasmic extracts showed that IFN-beta transcripts with elongated
      poly(A) tails were found in the nonpolysomal fractions, whereas the shorter
      transcripts could be detected in both polysomal and nonpolysomal fractions. A
      longer form of the IFN-beta mRNA was also found in the nonpolysomal fractions of
      cells not treated with transcriptional inhibitors. Thus, the observed regulation
      of IFN-beta mRNA is not entirely dependent on the inhibition of transcription. To
      our knowledge, this study provides the first example of a poly(A) tail elongation
      in somatic cells that negatively influences gene expression in vivo.

PMID- 8552073
TI  - Mutational analysis of the Saccharomyces cerevisiae ABD1 gene: cap
      methyltransferase activity is essential for cell growth.
AB  - RNA (guanine-7-)-methyltransferase is the enzyme responsible for methylating the
      5' cap structure of eukaryotic mRNA. The Saccharomyces cerevisiae enzyme is a 436
      amino-acid protein encoded by the essential ABD1 gene. In this study, deletion
      and point mutations in ABD1 were tested for the ability to support growth of an
      abd1 null strain. Elimination of 109 amino acids from the N terminus had no
      effect on cell viability, whereas a more extensive N-terminal deletion of 155
      residues was lethal, as was a C-terminal deletion of 55 amino acids. Alanine
      substitution mutations were introduced at eight conserved residues within a 206
      amino-acid region of similarity between ABD1 and the methyltransferase domain of
      the vaccinia virus capping enzyme. ABD1 alleles H253A (encoding a substitution of
      alanine for histidine at position 253), T282A, E287A, E361A, and Y362A were
      viable, whereas G174A, D178A, and Y254A were either lethal or severely defective
      for growth. Alanine-substituted and amino-truncated ABD1 proteins were expressed
      in bacteria, purified, and tested for cap methyltransferase activity in vitro.
      Mutations that were viable in yeast cells had either no effect or only a moderate
      effect on the specific methyltransferase activity of the mutated ABD1 protein,
      whereas mutations that were deleterious in vivo yielded proteins that were
      catalytically defective in vitro. These findings substantiate for the first time
      the long-held presumption that cap methylation is an essential function in
      eukaryotic cells.

PMID- 8552074
TI  - Transcriptional down regulation of the nov proto-oncogene in fibroblasts
      transformed by p60v-src.
AB  - We have sought to identify genes whose expression is altered as a consequence of
      transformation by p60v-src. Using the mRNA differential display method, we have
      identified the nov proto-oncogene as one gene that is down regulated in chicken
      embryo fibroblasts (CEFs) transformed by p60v-src. nov transcripts were also
      found to be present at only very low levels in proliferating CEFs in comparison
      with quiescent CEFs. Serum stimulation of quiescent CEFs also resulted in a
      decline in the steady-state level of nov transcripts. Taken together, these
      findings suggest that the nov gene is expressed only in quiescent fibroblasts and
      that its down regulation may contribute to cellular transformation by the v-src
      oncogene. Down regulation of the nov gene appears to occur at both the
      transcriptional and posttranscriptional levels. Results obtained from experiments
      with a protein kinase inhibitor suggest that protein kinase C may be a key
      downstream effector in mediating the down regulation of nov transcripts in
      response to activation of p60src or serum stimulation. In addition, we found that
      transcription of an unknown gene is required for the decline in the steady-state
      level of nov transcripts in response to serum stimulation.

PMID- 8552075
TI  - Wild-type p53 induces diverse effects in 32D cells expressing different
      oncogenes.
AB  - Expression of exogenous wild-type (wt) p53 in different leukemia cell lines can
      induce growth arrest, apoptotic cell death, or cell differentiation. The
      hematopoietic cell lines that have been used so far to study wt p53 functions
      have in common the characteristic of not expressing endogenous p53. However, the
      mechanisms involved in the transformation of these cells are different, and the
      cells are at different stages of tumor progression. It can be postulated that
      each type of neoplastic cell offers a particular environment in which p53 might
      generate different effects. To test this hypothesis, we introduced individual
      oncogenes into untransformed, interleukin-3 (IL-3)-dependent myeloid precursor
      32D cells to have a single transforming agent at a time. The effects induced by
      wt p53 overexpression were subsequently evaluated in each oncogene-expressing 32D
      derivative. We found that in not fully transformed, v-ras-expressing 32D cells,
      as already shown for the parental 32D cells, overexpression of the wt p53 gene
      caused no phenotypic changes and no reduction of the proliferative rate as long
      as the cells were maintained in their normal culture conditions (presence of IL-3
      and serum). An accelerated rate of apoptosis was observed after IL-3 withdrawal.
      In contrast, in transformed, IL-3-independent 32D cells, wt p53 overexpression
      induced different effects. The v-abl-transformed cells manifested a reduction in
      growth rate, while the v-src-transformed cells underwent monocytic
      differentiation. These results show that the phenotype effects of wt p53
      action(s) can vary as a function of the cellular environment.

PMID- 8552076
TI  - Double mutants of Saccharomyces cerevisiae with alterations in global genome and
      transcription-coupled repair.
AB  - The nucleotide excision repair (NER) pathway is thought to consist of two
      subpathways: transcription-coupled repair, limited to the transcribed strand of
      active genes, and global genome repair for nontranscribed DNA strands. Recently
      we cloned the RAD26 gene, the Saccharomyces cerevisiae homolog of human
      CSB/ERCC6, a gene involved in transcription-coupled repair and the disorder
      Cockayne syndrome. This paper describes the analysis of yeast double mutants
      selectively affected in each NER subpathway. Although rad26 disruption mutants
      are defective in transcription-coupled repair, they are not UV sensitive.
      However, double mutants of RAD26 with the global genome repair determinants RAD7
      and RAD16 appeared more UV sensitive than the single rad7 or rad16 mutants but
      not as sensitive as completely NER-deficient mutants. These findings unmask a
      role of RAD26 and transcription-coupled repair in UV survival, indicate that
      transcription-coupled repair and global genome repair are partially overlapping,
      and provide evidence for a residual NER modality in the double mutants. Analysis
      of dimer removal from the active RPB2 gene in the rad7/16 rad26 double mutants
      revealed (i) a contribution of the global genome repair factors Rad7p and Rad16p
      to repair of the transcribed strand, confirming the partial overlap between both
      NER subpathways, and (ii) residual repair specifically of the transcribed strand.
      To investigate the transcription dependence of this repair activity, strand
      specific repair of the inducible GAL7 gene was investigated. The template strand
      of this gene was repaired only under induced conditions, pointing to a role for
      transcription in the residual repair in the double mutants and suggesting that
      transcription-coupled repair can to some extent operate independently from
      Rad26p. Our findings also indicate locus heterogeneity for the dependence of
      transcription-coupled repair on RAD26.

PMID- 8552077
TI  - The major histocompatibility complex class II Ea promoter requires TFIID binding
      to an initiator sequence.
AB  - The major histocompatibility complex (MHC) class II Ea promoter is dependent on
      the presence of conserved upstream X and Y boxes and of initiator (Inr)
      sequences. In vitro transcription analysis of the Inr region with linker-scanning
      mutants pinpoints a functionally essential element that shows homology to the
      terminal deoxynucleotidyltransferase (TdT) Inr; contrary to the TdT Inr and other
      Inrs identified so far, the key sequence, between positions +5 and +12, is
      located within a transcribed area. Swapping the TdT sequence into the
      corresponding Ea position leads to a fivefold increase in transcription rate,
      without altering start site selection. Inr-binding proteins LBP-1/CP2 and TIP--a
      TdT Inr-binding protein unrelated to YY1--recognize the Ea Inr; they interact
      with overlapping yet distinct sequences around the Cap site, but their binding
      does not coincide with Ea Inr activity. A good correlation is, rather, found with
      binding of immunopurified holo-TFIID to this element. TFIID interacts both with
      Ea TATA-like and Inr sequences, but only the latter is functionally relevant.
      Unlike TBP, TFIID binds in the absence of TFIIA, indicating a stabilizing role
      for TBP-associated factors in Ea promoter recognition. Sequence comparison with
      other mouse and human MHC class II promoters suggests a common mechanism of start
      site(s) selection for the MHC class II gene family.

PMID- 8552078
TI  - Distinct cis-acting elements mediate clock, light, and developmental regulation
      of the Neurospora crassa eas (ccg-2) gene.
AB  - The Neurospora crassa eas (ccg-2) gene, which encodes a fungal hydrophobin, is
      transcriptionally regulated by the circadian clock. In addition, eas (ccg-2) is
      positively regulated by light and transcripts accumulate during asexual
      development. To sort out the basis of this complex regulation, deletion analyses
      of the eas (ccg-2) promoter were carried out to localize the cis-acting elements
      mediating clock, light, and developmental control. The primary sequence
      determinants of a positive activating clock element (ACE) were found to reside in
      a 45-bp region, just upstream from the TATA box. Using a novel unregulated
      promoter/reporter system developed for this study, we show that a 68-bp sequence
      encompassing the ACE is sufficient to confer clock regulation on the eas (ccg-2)
      gene. Electrophoretic mobility shift assays using the ACE reveal factors present
      in N. crassa protein extracts that recognize and bind specifically to DNA
      containing this element. Separate regions of the eas (ccg-2) promoter involved in
      light induction and developmental control are identified and shown not to be
      required for clock-regulated expression of eas (ccg-2). The distinct nature of
      the ACE validates its use as a tool for the identification of upstream regulatory
      factors involved in clock control of gene expression.

PMID- 8552079
TI  - Gene targeting of a plasmid-borne sequence to a double-strand DNA break in
      Drosophila melanogaster.
AB  - We report an efficient and specific gene targeting method for transforming the
      germ line of Drosophila melanogaster. The targeting occurs during the repair of a
      double-strand DNA break that is induced at the white locus by the excision of a P
      transposable element. The break is repaired when homologous sequence is copied
      from a plasmid injected into the Drosophila embryo. The procedure efficiently
      integrates DNA into the targeted locus of the Drosophila genome. Heterologous
      sequence of up to 13 kbp in length can be inserted, permitting the intergration
      of entire genes into a common genomic site for further study.

PMID- 8552080
TI  - A point mutation in the extracellular domain activates LET-23, the Caenorhabditis
      elegans epidermal growth factor receptor homolog.
AB  - The let-23 gene encodes a Caenorhabditis elegans homolog of the epidermal growth
      factor receptor (EGFR) necessary for vulval development. We have characterized a
      mutation of let-23 that activates the receptor and downstream signal
      transduction, leading to excess vulval differentiation. This mutation alters a
      conserved cysteine residue in the extracellular domain and is the first such
      point mutation in the EGFR subfamily of tyrosine kinases. Mutation of a different
      cysteine in the same subdomain causes a strong loss-of-function phenotype,
      suggesting that cysteines in this region are important for function and
      nonequivalent. Vulval precursor cells can generate either of two subsets of
      vulval cells (distinct fates) in response to sa62 activity. The fates produced
      depended on the copy number of the mutation, suggesting that quantitative
      differences in receptor activity influence the decision between these two fates.

PMID- 8552081
TI  - Ras-mediated phosphorylation of a conserved threonine residue enhances the
      transactivation activities of c-Ets1 and c-Ets2.
AB  - The Ras oncogene products regulate the expression of genes in transformed cells,
      and members of the Ets family of transcription factors have been implicated in
      this process. To determine which Ets factors are the targets of Ras signaling
      pathways, the abilities of several Ets factors to activate Ras-responsive
      enhancer (RRE) reporters in the presence of oncogenic Ras were examined. In
      transient transfection assay, reporters containing RREs composed of Ets-AP-1
      binding sites could be activated 30-fold in NIH 3T3 fibroblasts and 80-fold in
      the macrophage-like line RAW264 by the combination of Ets1 or Ets2 and Ras but
      not by several other Ets factors that were tested in the assay. Ets2 and Ras also
      superactivated an RRE composed of Ets-Ets binding sites, but the Ets-responsive
      promoter of the c-fms gene was not superactivated. Mutation of a threonine
      residue to alanine in the conserved amino-terminal regions of Ets1 and Ets2
      (threonine 38 and threonine 72, respectively) abrogated the ability of each of
      these proteins to superactivate reporter gene expression. Phosphoamino acid
      analysis of radiolabeled Ets2 revealed that Ras induced normally absent threonine
      specific phosphorylation of the protein. The Ras-dependent increase in threonine
      phosphorylation was not observed in Ets2 proteins that had the conserved
      threonine 72 residue mutated to alanine or serine. These data indicate that Ets1
      and Ets2 are specific nuclear targets of Ras signaling events and that
      phosphorylation of a conserved threonine residue is a necessary molecular
      component of Ras-mediated activation of these transcription factors.

PMID- 8552082
TI  - A conserved proline-rich region of the Saccharomyces cerevisiae cyclase
      associated protein binds SH3 domains and modulates cytoskeletal localization.
AB  - Saccharomyces cerevisiae cyclase-associated protein (CAP or Srv2p) is
      multifunctional. The N-terminal third of CAP binds to adenylyl cyclase and has
      been implicated in adenylyl cyclase activation in vivo. The widely conserved C
      terminal domain of CAP binds to monomeric actin and serves an important
      cytoskeletal regulatory function in vivo. In addition, all CAP homologs contain a
      centrally located proline-rich region which has no previously identified
      function. Recently, SH3 (Src homology 3) domains were shown to bind to proline
      rich regions of proteins. Here we report that the proline-rich region of CAP is
      recognized by the SH3 domains of several proteins, including the yeast actin
      associated protein Abp1p. Immunolocalization experiments demonstrate that CAP
      colocalizes with cortical actin-containing structures in vivo and that a region
      of CAP containing the SH3 domain binding site is required for this localization.
      We also demonstrate that the SH3 domain of yeast Abp1p and that of the yeast RAS
      protein guanine nucleotide exchange factor Cdc25p complex with adenylyl cyclase
      in vitro. Interestingly, the binding of the Cdc25p SH3 domain is not mediated by
      CAP and therefore may involve direct binding to adenylyl cyclase or to an
      unidentified protein which complexes with adenylyl cyclase. We also found that
      CAP homologous from Schizosaccharomyces pombe and humans bind SH3 domains. The
      human protein binds most strongly to the SH3 domain from the abl proto-oncogene.
      These observations identify CAP as an SH3 domain-binding protein and suggest that
      CAP mediates interactions between SH3 domain proteins and monomeric actin.

PMID- 8552083
TI  - The species-specific RNA polymerase I transcription factor SL-1 binds to upstream
      binding factor.
AB  - Transcription of the 45S rRNA genes is carried out by RNA polymerase I and at
      least two trans-acting factors, upstream binding factor (UBF) and SL-1. We have
      examined the hypothesis that SL-1 and UBF interact. Coimmunoprecipitation studies
      using an antibody to UBF demonstrated that TATA-binding protein, a subunit of SL
      1, associates with UBF in the absence of DNA. Inclusion of the detergents sodium
      dodecyl sulfate and deoxycholate disrupted this interaction. In addition,
      partially purified UBF from rat cell nuclear extracts and partially purified SL-1
      from human cells coimmunoprecipitated with the anti-UBF antibody after mixing,
      indicating that the UBF-SL-1 complex can re-form. Treatment of UBF-depleted
      extracts with the anti-UBF antibody depleted the extracts of SL-1 activity only
      if UBF was added to the extract prior to the immunodepletion reaction.
      Furthermore, SL-1 activity could be recovered in the immunoprecipitate.
      Interestingly, these immunoprecipitates did not contain RNA polymerase I, as a
      monospecific antibody to the 194-kDa subunit of RNA polymerase I failed to detect
      that subunit in the immunoprecipitates. Treatment of N1S1 cell extracts with the
      anti-UBF antibody depleted the extracts of SL-1 activity but not TFIIIB activity,
      suggesting that the binding of UBF to SL-1 is specific and not solely mediated by
      an interaction between UBF and TATA-binding protein, which is also a component of
      TFIIIB. These data provide evidence that UBF and SL-1 interact.

PMID- 8552084
TI  - Nucleus-encoded histone H1-like proteins are associated with kinetoplast DNA in
      the trypanosomatid Crithidia fasciculata.
AB  - Kinetoplast DNA (kDNA), the mitochondrial DNA of trypanosomatids, consists of
      thousands of minicircles and 20 to 30 maxicircles catenated into a single large
      network and exists in the cell as a highly organized compact disc structure. To
      investigate the role of kinetoplast-associated proteins in organizing and
      condensing kDNA networks into this disc structure, we have cloned three genes
      encoding kinetoplast-associated proteins. The KAP2, KAP3, and KAP4 genes encode
      proteins p18, p17, and p16, respectively. These proteins are small basic proteins
      rich in lysine and alanine residues and contain 9-amino-acid cleavable
      presequences. Proteins p17 and p18 are closely related to each other, with 48%
      identical residues and carboxyl tails containing almost exclusively lysine,
      alanine, and serine or threonine residues. These proteins have been expressed as
      Met-His6-tagged recombinant proteins and purified by metal chelate
      chromatography. Each of the recombinant proteins is capable of compacting kDNA
      networks in vitro and was shown to bind preferentially to a specific fragment of
      minicircle DNA. Expression of each of these proteins in an Escherichia coli
      mutant lacking the HU protein rescued a defect in chromosome condensation and
      segregation in the mutant cells and restored a near-normal morphological
      appearance. Proteins p16, p17, and p18 have been localized within the cell by
      immunofluorescence methods and appear to be present throughout the kDNA. Electron
      microscopic immunolocalization of p16 shows that p16 is present both within the
      kDNA disc and in the mitochondrial matrix at opposite edges of the kDNA disc. Our
      results suggest that nucleus-encoded H1-like proteins may be involved in the
      organization and segregation of kDNA networks in trypanosomatids.

PMID- 8552085
TI  - Insulin stimulation of a MEK-dependent but ERK-independent SOS protein kinase.
AB  - The Ras guanylnucleotide exchange protein SOS undergoes feedback phosphorylation
      and dissociation from Grb2 following insulin receptor kinase activation of Ras.
      To determine the serine/threonine kinase(s) responsible for SOS phosphorylation
      in vivo, we assessed the role of mitogen-activated, extracellular-signal
      regulated protein kinase kinase (MEK), extracellular-signal-regulated protein
      kinase (ERK), and the c-JUN protein kinase (JNK) in this phosphorylation event.
      Expression of a dominant-interfering MEK mutant, in which lysine 97 was replaced
      with arginine (MEK/K97R), resulted in an inhibition of insulin-stimulated SOS and
      ERK phosphorylation, whereas expression of a constitutively active MEK mutant, in
      which serines 218 and 222 were replaced with glutamic acid (MEK/EE), induced
      basal phosphorylation of both SOS and ERK. Although expression of the mitogen
      activated protein kinase-specific phosphatase (MKP-1) completely inhibited the
      insulin stimulation of ERK activity both in vitro and in vivo, SOS
      phosphorylation and the dissociation of the Grb2-SOS complex were unaffected. In
      addition, insulin did not activate the related protein kinase JNK, demonstrating
      the specificity of insulin for the ERK pathway. The insulin-stimulated and MKP-1
      insensitive SOS-phosphorylating activity was reconstituted in whole-cell extracts
      and did not bind to a MonoQ anion-exchange column. In contrast, ERK1/2 protein
      was retained by the MonoQ column, eluted with approximately 200 mM NaCl, and was
      MKP-1 sensitive. Although MEK also does not bind to MonoQ, immunodepletion
      analysis demonstrated that MEK is not the insulin-stimulated SOS-phosphorylating
      activity. Together, these data demonstrate that at least one of the kinases
      responsible for SOS phosphorylation and functional dissociation of the Grb2-SOS
      complex is an ERK-independent but MEK-dependent insulin-stimulated protein
      kinase.

PMID- 8552086
TI  - A composite element binding the vitamin D receptor, retinoid X receptor alpha,
      and a member of the CTF/NF-1 family of transcription factors mediates the vitamin
      D responsiveness of the c-fos promoter.
AB  - The hormonal form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 [1,25- (OH)2D3],
      transiently stimulates the transcription of the c-fos proto-oncogene in
      osteoblastic cells. We have identified and characterized a vitamin D response
      element (VDRE) in the promoter of c-fos. The 1,25-(OH)2D3-responsive region was
      delineated between residues -178 and -144 upstream of the c-fos transcription
      start site. A mutation that inhibited binding to the sequence concomitantly
      abolished 1,25-(OH)2D3-induced transcriptional responsiveness; similarly, cloning
      to the site upstream of a heterologous promoter conferred copy-number-dependent
      vitamin D responsiveness to a reporter gene, demonstrating that we have
      identified a functional response element. The structure of the c-fos VDRE was
      found to be unusual. Mutational analysis revealed that the c-fos VDRE does not
      conform to the direct repeat configuration in which hexameric core-binding sites
      are spaced by a few nucleotide residues. In contrast, the entire 36-bp sequence
      was essential for binding. We identified the vitamin D receptor and the retinoid
      X receptor alpha as components of the complex that bound the c-fos VDRE. However,
      our results also show that a putative CCAAT-binding transcription factor/nuclear
      factor 1 (CTF/NF-1) family member bound the response element in conjunction with
      the nuclear hormone receptors. The expression of this CTF/NF-1 family member
      appeared restricted to bone cells. These data hint at new molecular mechanisms of
      action for vitamin D.

PMID- 8552087
TI  - Identification of human proteins functionally conserved with the yeast putative
      adaptors ADA2 and GCN5.
AB  - Transcriptional adaptor proteins are required for full function of higher
      eukaryotic acidic activators in the yeast Saccharomyces cerevisiae, suggesting
      that this pathway of activation is evolutionarily conserved. Consistent with this
      view, we have identified possible human homologs of yeast ADA2 (yADA2) and yeast
      GCN5 (yGCN5), components of a putative adaptor complex. While there is overall
      sequence similarity between the yeast and human proteins, perhaps more
      significant is conservation of key sequence features with other known adaptors.
      We show several functional similarities between the human and yeast adaptors.
      First, as shown for yADA2 and yGCN5, human ADA2 (hADA2) and human GCN5 (hGCN5)
      interacted in vivo in a yeast two-hybrid assay. Moreover, hGCN5 interacted with
      yADA2 in this assay, suggesting that the human proteins form similar complexes.
      Second, both yADA2 and hADA2 contain cryptic activation domains. Third, hGCN5 and
      yGCN5 had similar stabilizing effects on yADA2 in vivo. Furthermore, the region
      of yADA2 that interacted with yGCN5 mapped to the amino terminus of yADA2, which
      is highly conserved in hADA2. Most striking, is the behavior of the human
      proteins in human cells. First, GAL4-hADA2 activated transcription in HeLa cells,
      and second, either hADA2 or hGCN5 augmented GAL4-VP16 activation. These data
      indicated that the human proteins correspond to functional homologs of the yeast
      adaptors, suggesting that these cofactors play a key role in transcriptional
      activation.

PMID- 8552088
TI  - Coding sequence-dependent ribosomal arrest at termination of translation.
AB  - A remarkably high percentage of proto-oncogene, growth factor, cellular receptor,
      and viral transcript leaders contain short upstream open reading frames (uORFs),
      yet the significance and regulatory effects of these uORFs have not been well
      characterized. In the case of the human cytomegalovirus gpUL4 (gp48) transcript,
      the second of three uORFs (uORF2) inhibits translation of the downstream cistron
      by a process that depends on the uORF2 amino acid coding information. To
      investigate the mechanism underlying this unusual regulatory element, we adapted
      the toeprinting (or reverse transcriptase extension inhibition) assay for use in
      detecting positions of ribosomal stalling on gp48 transcripts. Using a cell-free
      translation system, we demonstrate that ribosomes arrest at the termination codon
      of uORF2 by a uORF2 coding sequence-dependent mechanism. Further, the sequence
      requirements for ribosomal stalling are the same as for inhibition of downstream
      translation. We also provide evidence for ribosomal stalling in vivo, on the
      natural viral mRNA. These data support the hypothesis that the inhibition of
      downstream translation results from uORF2 peptide-dependent ribosomal arrest at
      termination and suggest that translation termination may be a regulatory step in
      expression of some eukaryotic genes.

PMID- 8552089
TI  - T-cell receptor alpha locus V(D)J recombination by-products are abundant in
      thymocytes and mature T cells.
AB  - In addition to the assembled coding regions of immunoglobulin and T-cell receptor
      (TCR) genes, the V(D)J recombination reaction can in principle generate three
      types of by-products in normal developing lymphocytes: broken DNA molecules that
      terminate in a recombination signal sequence or a coding region (termed signal or
      coding end molecules, respectively) and DNA molecules containing fused
      recombination signal sequences (termed reciprocal products). Using a quantitative
      Southern blot analysis of the murine TCR alpha locus, we demonstrate that
      substantial amounts of signal end molecules and reciprocal products, but not
      coding end molecules, exist in thymocytes, while peripheral T cells contain
      substantial amounts of reciprocal products. At the 5' end of the J alpha locus,
      20% of thymus DNA exists as signal end molecules. An additional 30 to 40% of the
      TCR alpha/delta locus exists as remarkably stable reciprocal products throughout
      T-cell development, with the consequence that the TCR C delta region is
      substantially retained in alpha beta committed T cells. The disappearance of the
      broken DNA molecules occurs in the same developmental transition as termination
      of expression of the recombination activating genes, RAG-1 and RAG-2. These
      findings raise important questions concerning the mechanism of V(D)J
      recombination and the maintenance of genome integrity during lymphoid
      development.

PMID- 8552090
TI  - An intestine-specific homeobox gene regulates proliferation and differentiation.
AB  - Precise regulation of cellular proliferation, differentiation, and senescence
      results in the continuous renewal of the intestinal epithelium with maintenance
      of a highly ordered tissue architecture. Here we show that an intestine-specific
      homeobox gene, Cdx2, is a transcription factor that regulates both proliferation
      and differentiation in intestinal epithelial cells. Conditional expression of
      Cdx2 in IEC-6 cells, an undifferentiated intestinal cell line, led to arrest of
      proliferation for several days followed by a period of growth resulting in
      multicellular structures containing a well-formed columnar layer of cells. The
      columnar cells had multiple morphological characteristics of intestinal
      epithelial cells. Enterocyte-like cells were polarized with tight junctions,
      lateral membrane interdigitations, and well-organized microvilli with associated
      glycocalyx located at the apical pole. Remarkably, there were also cells with a
      goblet cell-like ultrastructure, suggesting that two of the four intestinal
      epithelial cell lineages may arise from IEC-6 cells. Molecular evidence for
      differentiation was shown by demonstrating that cells expressing high levels of
      Cdx2 expressed sucrase-isomaltase, an enterocyte-specific gene which is a well
      defined target for the Cdx2 protein. Taken together, our data suggest that Cdx2
      may play a role in directing early processes in intestinal cell morphogenesis and
      in the maintenance of the differentiated phenotype by supporting transcription of
      differentiated gene products. We propose that Cdx2 is part of a regulatory
      network that orchestrates a developmental program of proliferation,
      morphogenesis, and gene expression in the intestinal epithelium.

PMID- 8552091
TI  - BETA3, a novel helix-loop-helix protein, can act as a negative regulator of BETA2
      and MyoD-responsive genes.
AB  - Using degenerate PCR cloning we have identified a novel basic helix-loop-helix
      (bHLH) transcription factor, BETA3, from a hamster insulin tumor (HIT) cell cDNA
      library. Sequence analysis revealed that this factor belongs to the class B bHLH
      family and has the highest degree of homology with another bHLH transcription
      factor recently isolated in our laboratory, BETA2 (neuroD) (J. E. Lee, S. M.
      Hollenberg, L. Snider, D. L. Turner, N. Lipnick, and H. Weintraub, Science
      268:836-844, 1995; F. J. Naya, C. M. M. Stellrecht, and M.-J. Tsai, Genes Dev.
      8:1009-1019, 1995). BETA2 is a brain- and pancreatic-islet-specific bHLH
      transcription factor and is largely responsible for the tissue-specific
      expression of the insulin gene. BETA3 was found to be tissue restricted, with the
      highest levels of expression in HIT, lung, kidney, and brain cells. Surprisingly,
      despite the homology between BETA2 and BETA3 and its intact basic region, BETA3
      is unable to bind the insulin E box in bandshift analysis as a homodimer or as a
      heterodimer with the class A bHLH factors E12, E47, or BETA1. Instead, BETA3
      inhibited both the E47 homodimer and the E47/BETA2 heterodimer binding to the
      insulin E box. In addition, BETA3 greatly repressed the BETA2/E47 induction of
      the insulin enhancer in HIT cells as well as the MyoD/E47 induction of a muscle
      specific E box in the myoblast cell line C2C12. In contrast, expression of BETA3
      had no significant effect on the GAL4-VP16 transcriptional activity.
      Immunoprecipitation analysis demonstrates that the mechanism of repression is via
      direct protein-protein interaction, presumably by heterodimerization between
      BETA3 and class A bHLH factors.

PMID- 8552092
TI  - Protein-DNA interactions at the major and minor promoters of the divergently
      transcribed dhfr and rep3 genes during the Chinese hamster ovary cell cycle.
AB  - In mammals, two TATA-less bidirectional promoters regulate expression of the
      divergently transcribed dihydrofolate reductase (dhfr) and rep3 genes. In CHOC
      400 cells, dhfr mRNA levels increase about fourfold during the G1-to-S phase
      transition of the cell cycle, whereas the levels of rep3 transcripts vary less
      than twofold during this time. To assess the role of DNA-binding proteins in
      transcriptional regulation of the dhfr and rep3 genes, the major and minor dhfr
      rep3 promoter regions were analyzed by high-resolution genomic footprinting
      during the cell cycle. At the major dhfr promoter, prominent DNase I footprints
      over four upstream Sp1 binding sites did not vary throughout G1 and entry into
      the S phase. Genomic footprinting revealed that a protein is constitutively bound
      to the overlapping E2F sites throughout the G1-to-S phase transition, an
      interaction that is most evident on the transcribed template strand. On the
      nontranscribed strand, multiple changes in the DNase I cleavage pattern are
      observed during transit through G1 and entry into the S phase. By using gel
      mobility shift assays and a series of sequence-specific probes, two different
      species of E2F were shown to interact with the dhfr promoter during the cell
      cycle. The DNA binding activity of one E2F species, which preferentially
      recognizes the sequence TTTGGCGC, did not vary significantly during the cell
      cycle. The DNA binding activity of the second E2F species, which preferentially
      recognizes the sequence TTTCGCGC, increased during the G1-to-S phase transition.
      Together, these results indicate that Sp1 and the species of E2F that binds
      TTTGGCGC participate in the formation of a basal transcription complex, while the
      species of E2F that binds TTTCGCGC regulates dhfr gene expression during the G1
      to-S phase transition. At the minor promoter, DNase I footprints at a consensus c
      Myc binding site and three Sp1 binding sites showed little variation during the
      G1-to-S phase transition. In addition to protein binding at sequences known to be
      involved in the regulation of transcription, genomic footprinting of the entire
      promoter region also showed that a protein factor is constitutively bound to the
      first intron of the rep3 gene.

PMID- 8552093
TI  - GTPase-deficient G alpha 16 and G alpha q induce PC12 cell differentiation and
      persistent activation of cJun NH2-terminal kinases.
AB  - Persistent stimulation of specific protein kinase pathways has been proposed as a
      key feature of receptor tyrosine kinases and intracellular oncoproteins that
      signal neuronal differentiation of rat pheochromocytoma (PC12) cells. Among the
      protein serine/threonine kinases identified to date, the p42/44 mitogen-activated
      protein (MAP) kinases have been highlighted for their potential role in
      signalling PC12 cell differentiation. We report here that retrovirus-mediated
      expression of GTPase-deficient, constitutively active forms of the heterotrimeric
      Gq family members, G alpha qQ209L and G alpha 16Q212L, in PC12 cells induces
      neuronal differentiation as indicated by neurite outgrowth and the increased
      expression of voltage-dependent sodium channels. Differentiation was not observed
      after cellular expression of GTPase-deficient forms of alpha i2 or alpha 0,
      indicating selectivity for the Gq family of G proteins. As predicted,
      overexpression of alpha qQ209L and alpha 16Q212L constitutively elevated basal
      phospholipase C activity approximately 10-fold in PC12 cells. Significantly,
      little or no p42/44 MAP kinase activity was detected in PC12 cells differentiated
      with alpha 16Q212L or alpha qQ209L, although these proteins were strongly
      activated following expression of constitutively active cRaf-1. Rather, a
      persistent threefold activation of the cJun NH2-terminal kinases (JNKs) was
      observed in PC12 cells expressing alpha qQ209L and alpha 16Q212L. This level of
      JNK activation was similar to that achieved with nerve growth factor, a strong
      inducer of PC12 cell differentiation. Supportive of a role for JNK activation in
      PC12 cell differentiation, retrovirus-mediated overexpression of cJun, a JNK
      target, in PC12 cells induced neurite outgrowth. The results define a p42/44 MAP
      kinase-independent mechanism for differentiation of PC12 cells and suggest that
      persistent activation of the JNK members of the proline-directed protein kinase
      family by GTPase-deficient G alpha q and G alpha 16 subunits is sufficient to
      induce differentiation of PC12 cells.

PMID- 8552094
TI  - Mechanism of MAT alpha donor preference during mating-type switching of
      Saccharomyces cerevisiae.
AB  - During homothallic switching of the mating-type (MAT) gene in Saccharomyces
      cerevisiae, a- or alpha-specific sequences are replaced by opposite mating-type
      sequences copied from one of two silent donor loci, HML alpha or HMRa. The two
      donors lie at opposite ends of chromosome III, approximately 190 and 90 kb,
      respectively, from MAT. MAT alpha cells preferentially recombine with HMR, while
      MATa cells select HML. The mechanisms of donor selection are different for the
      two mating types. MATa cells, deleted for the preferred HML gene, efficiently use
      HMR as a donor. However, in MAT alpha cells, HML is not an efficient donor when
      HMR is deleted; consequently, approximately one-third of HO HML alpha MAT alpha
      hmr delta cells die because they fail to repair the HO endonuclease-induced
      double-strand break at MAT. MAT alpha donor preference depends not on the
      sequence differences between HML and HMR or their surrounding regions but on
      their chromosomal locations. Cloned HMR donors placed at three other locations to
      the left of MAT, on either side of the centromere, all fail to act as efficient
      donors. When the donor is placed 37 kb to the left of MAT, its proximity
      overcomes normal donor preference, but this position is again inefficiently used
      when additional DNA is inserted in between the donor and MAT to increase the
      distance to 62 kb. Donors placed to the right of MAT are efficiently recruited,
      and in fact a donor situated 16 kb proximal to HMR is used in preference to HMR.
      The cis-acting chromosomal determinants of MAT alpha preference are not
      influenced by the chromosomal orientation of MAT or by sequences as far as 6 kb
      from HMR. These data argue that there is an alpha-specific mechanism to inhibit
      the use of donors to the left of MAT alpha, causing the cell to recombine most
      often with donors to the right of MAT alpha.

PMID- 8552095
TI  - Paf1p, an RNA polymerase II-associated factor in Saccharomyces cerevisiae, may
      have both positive and negative roles in transcription.
AB  - Regulated transcription initiation requires, in addition to RNA polymerase II and
      the general transcription factors, accessory factors termed mediators or
      adapters. We have used affinity chromatography to identify a collection of
      factors that associate with Saccharomyces cerevisiae RNA polymerase II (P. A.
      Wade, W. Werel, R. C. Fentzke, N. E. Thompson, J. F. Leykam, R. R. Burgess, J. A.
      Jaehning, and Z. F. Burton, submitted for publication). Here we report
      identification and characterization of a gene encoding one of these factors, PAF1
      (for RNA polymerase-associated factor 1). PAF1 encodes a novel, highly charged
      protein of 445 amino acids. Disruption of PAF1 in S. cerevisiae leads to
      pleiotropic phenotypic traits, including slow growth, temperature sensitivity,
      and abnormal cell morphology. Consistent with a possible role in transcription,
      Paf1p is localized to the nucleus. By comparing the abundances of many yeast
      transcripts in isogenic wild-type and paf1 mutant strains, we have identified
      genes whose expression is affected by PAF1. In particular, disruption of PAF1
      decreases the induction of the galactose-regulated genes three- to fivefold. In
      contrast, the transcript level of MAK16, an essential gene involved in cell cycle
      regulation, is greatly increased in the paf1 mutant strain. Paf1p may therefore
      be required for both positive and negative regulation of subsets of yeast genes.
      Like Paf1p, the GAL11 gene product is found associated with RNA polymerase II and
      is required for regulated expression of many yeast genes including those
      controlled by galactose. We have found that a gal11 paf1 double mutant has a much
      more severe growth defect than either of the single mutants, indicating that
      these two proteins may function in parallel pathways to communicate signals from
      regulatory factors to RNA polymerase II.

PMID- 8552096
TI  - Identification of a positive regulator of the cell cycle ubiquitin-conjugating
      enzyme Cdc34 (Ubc3).
AB  - The Cdc34 (Ubc3) ubiquitin-conjugating enzyme from Saccharomyces cerevisiae plays
      an essential role in the progression of cells from the G1 to S phase of the cell
      division cycle. Using a high-copy suppression strategy, we have identified a
      yeast gene (UBS1) whose elevated expression suppresses the conditional cell cycle
      defects associated with cdc34 mutations. The UBS1 gene encodes a 32.2-kDa protein
      of previously unknown function and is identical in sequence to a genomic open
      reading frame on chromosome II (GenBank accession number Z36034). Several lines
      of evidence described here indicate that Ubs1 functions as a general positive
      regulator of Cdc34 activity. First, overexpression of UBS1 suppresses not only
      the cell proliferation and morphological defects associated with cdc34 mutants
      but also the inability of cdc34 mutant cells to degrade the general amino acid
      biosynthesis transcriptional regulator, Gcn4. Second, deletion of the UBS1 gene
      profoundly accentuates the cell cycle defect when placed in combination with a
      cdc34 temperature-sensitive allele. Finally, a comparison of the Ubs1 and Cdc34
      polypeptide sequences reveals two noncontiguous regions of similarity, which,
      when projected onto the three-dimensional structure of a ubiquitin-conjugating
      enzyme, define a single region situated on its surface. While cdc34 mutations
      corresponding to substitutions outside this region are suppressed by UBS1
      overexpression, Ubs1 fails to suppress amino acid substitutions made within this
      region. Taken together with other findings, the allele specificity exhibited by
      UBS1 expression suggests that Ubs1 regulates Cdc34 by interaction or
      modification.

PMID- 8552097
TI  - E2F-1 blocks terminal differentiation and causes proliferation in transgenic
      megakaryocytes.
AB  - The transcription factor E2F-1 plays a central role in the cell cycle through its
      ability to activate genes involved in cell division. E2F-1 activity is regulated
      by a number of proteins, including the retinoblastoma susceptibility gene
      product, cyclin-dependent kinases, and their inhibitors, proteins that have been
      implicated in the control of certain developmental processes. To investigate a
      potential role of E2F-1 in differentiation, we assayed the ability of
      megakaryocytes to form platelets in an in vivo transgenic model. E2F-1 expression
      in megakaryocytes blocked differentiation during maturation, resulting in severe
      thrombocytopenia. Ultrastructural analysis of megakaryocytes revealed abnormal
      development characterized by hyperdemarcation of cytoplasmic membranes and
      reduced numbers of alpha granules. Administration of megakaryocyte growth and
      development factor or interleukin 6 could not overcome the differentiation block.
      Additionally, E2F-1 caused massive megakaryocyte accumulation in both normal and
      ectopic sites, first evident in E15 embryonic liver. Furthermore, significant
      apoptosis was observed in transgenic megakaryocytes. These data indicate that E2F
      1 can prevent terminal differentiation, probably through its cell cycle
      stimulatory activity.

PMID- 8552098
TI  - Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding
      protein via a direct mechanism.
AB  - We have characterized a phosphoserine binding domain in the coactivator CREB
      binding protein (CBP) which interacts with the protein kinase A-phosphorylated,
      and hence activated, form of the cyclic AMP-responsive factor CREB. The CREB
      binding domain, referred to as KIX, is alpha helical and binds to an unstructured
      kinase-inducible domain in CREB following phosphorylation of CREB at Ser-133.
      Phospho-Ser-133 forms direct contacts with residues in KIX, and these contacts
      are further stabilized by hydrophobic residues in the kinase-inducible domain
      which flank phospho-Ser-133. Like the src homology 2 (SH2) domains which bind
      phosphotyrosine-containing peptides, phosphoserine 133 appears to coordinate with
      a single arginine residue (Arg-600) in KIX which is conserved in the CBP-related
      protein P300. Since mutagenesis of Arg-600 to Gln severely reduces CREB-CBP
      complex formation, our results demonstrate that, as in the case of tyrosine
      kinase pathways, signal transduction through serine/threonine kinase pathways may
      also require protein interaction motifs which are capable of recognizing
      phosphorylated amino acids.

PMID- 8552099
TI  - Schizosaccharomyces pombe pcr1+ encodes a CREB/ATF protein involved in regulation
      of gene expression for sexual development.
AB  - The Schizosaccharomyces pombe pcr1 gene encodes a bZIP protein that apparently
      belongs to the cyclic AMP response element (CRE)-binding protein/activating
      transcription factor family. The deduced pcr1 gene product consists of 171 amino
      acid residues and is most similar to the mammalian CRE-BP1. A glutathione S
      transferase-Pcr1 fusion protein produced in Escherichia coli was able to bind
      specifically to the CRE motif in vitro. Analysis with anti-Pcr1 serum suggested
      that Pcr1 is included in the major CRE-binding factors present in the S. pombe
      cell extract. Disruption of the pcr1 gene was not lethal, but the disruptant
      showed cold-sensitive growth on rich medium. The disruptant was also inefficient
      in mating and sporulation, though it was not completely sterile. Expression of
      the ste11 gene, which encodes a key transcription factor for sexual development,
      was greatly reduced in the disruptant, and overexpression of ste11+ suppressed
      the deficiency of the pcr1 disruptant in sexual development. It has been shown
      that expression of ste11 is negatively regulated by cyclic AMP-dependent protein
      kinase (PKA) and that the loss of PKA activity results in ectopic sexual
      development. Disruption of pcr1 blocked ectopic sexual development. Furthermore,
      disruption of pcr1 reduced expression of fbp1, a glucose-repressible gene
      negatively regulated by PKA. These results suggest that Pcr1 is a putative
      transcriptional regulator whose activity may be controlled by PKA. Alternatively,
      its activity may be independent of PKA, and full induction of ste11 and fbp1
      expression requires the function of Pcr1 in addition to elimination of the
      repression by PKA.

PMID- 8552100
TI  - Cell-type-specific expression of the platelet-derived growth factor alpha
      receptor: a role for GATA-binding protein.
AB  - Platelet-derived growth factor alpha receptor (PDGF alpha R) is a transmembrane
      tyrosine kinase receptor for all three existing PDGF isoforms, AA, AB, and BB.
      Transcripts of PDGF alpha R are detected as early as in fertilized mouse eggs and
      throughout adulthood in a time- and space-specific manner, thereby suggesting an
      important role of PDGFs in mammalian development. In this study, we have
      investigated the mechanism involved in cell-type-specific PDGF alpha R gene
      expression during early embryonic development. Using F9 embryonic carcinoma cells
      as an in vitro study model, we identified a differentiation-dependent enhancer
      element within the PDGF alpha R promoter that controlled receptor expression
      during parietal endoderm cell differentiation induced by retinoic acid and
      dibutyryl cyclic AMP treatment. The differentiation-dependent enhancer element
      sequence bore no resemblance to consensus DNA-binding sites of either the
      retinoic acid receptor family or the cyclic AMP-responsive element-binding
      protein family. It was composed of two identical 12-bp direct repeats separated
      by a 17-bp insert sequence enriched in C and A nucleotides. Although only a
      single repeat was needed to form specific DNA-protein complexes with factors
      present in F9 parietal endoderm cell extracts, both repeats together were
      necessary to display cell-type-specific enhancing activity. Mutational analysis
      revealed that the protein-binding sites within the repeat sequences were
      identical to GATA-binding sites. In this study, we provided evidence to suggest
      that a member of the GATA transcription factor family (GATA-4) is responsible for
      parietal endoderm-specific PDGF alpha R expression.

PMID- 8552102
TI  - International Classification of Diseases, tenth revision: neurological adaptation
      (ICD-10 NA): extrapyramidal and movement disorders.
AB  - A classification of diseases is important in epidemiologic studies, indexing of
      clinical disorders, communication, and education. Since the 10th revision of the
      International Classification of Diseases (ICD-10) in 1992, a specialty-based
      neurological adaptation (ICD-10NA) has been developed to reflect the specific
      needs of individual subspecialties. Although the revision was constrained by the
      need to maintain compatibility with previous classifications, the new ICD-10NA of
      Extrapyramidal and Movement Disorders aims to provide an updated and
      comprehensive categorization of movement disorders.

PMID- 8552101
TI  - Autoactivation by a Candida glabrata copper metalloregulatory transcription
      factor requires critical minor groove interactions.
AB  - Rapid transcriptional autoactivation of the Candida glabrata AMT1 copper
      metalloregulatory transcription factor gene is essential for survival in the
      presence of high extracellular copper concentrations. Analysis of the
      interactions between purified recombinant AMT1 protein and the AMT1 promoter
      metal regulatory element was carried out by a combination of missing-nucleoside
      analysis, ethylation interference, site-directed mutagenesis, and quantitative in
      vitro DNA binding studies. The results of these experiments demonstrate that
      monomeric AMT1 binds the metal regulatory element with very high affinity and
      utilizes critical contacts in both the major and minor grooves. A single
      adenosine residue in the minor groove, conserved in all known yeast Cu
      metalloregulatory transcription factor DNA binding sites, plays a critical role
      in both AMT1 DNA binding in vitro and Cu-responsive AMT1 gene transcription in
      vivo. Furthermore, a mutation in the AMT1 Cu-activated DNA binding domain which
      converts a single arginine, found in a conserved minor groove binding domain, to
      lysine markedly reduces AMT1 DNA binding affinity in vitro and results in a
      severe defect in the ability of C. glabrata cells to mount a protective response
      against Cu toxicity.

PMID- 8552103
TI  - The epidemiology of Parkinson's disease in the county of Rogaland, Norway.
AB  - The objective of this investigation was to clarify the epidemiology of idiopathic
      Parkinson's disease (PD) in the county of Rogaland, Norway. Total case
      ascertainment and a high diagnostic accuracy were attempted through a detailed
      community study and the use of a new clinical diagnostic classification. The
      study population comprised 220,858 inhabitants, and a total of nearly 400
      patients was interviewed and examined by a neurologist. On prevalence day,
      January 1, 1993, 245 patients were included in the study. The diagnostic
      classification revealed 135 patients with clinically definite, 74 with probable,
      and 36 with possible PD. The crude prevalence rate was shown to be 110.9 per
      100,000 inhabitants. The total age-adjusted prevalence was calculated to be 102.4
      per 100,000 and to 120.9 per 100,000 men and 89.8 per 100,000 women. Among the
      245 patients, 28 patients had a tremor-dominant disease, 50 patients an akinetic
      dominant disease, and 167 patients a mixed clinical pattern of PD. Age-adjusted
      prevalence figures were slightly higher for rural compared to urban areas. About
      50% of the PD patients were in need of public help, 15% had complaints about pain
      related to their parkinsonism, and after approximately 6 years of levodopa
      treatment, 20% were suffering from clinical fluctuations. The study showed that
      40% of the patients had some degree of thought disorder. The prevalence figures
      for PD in this study are slightly lower than those reported from most previous
      prevalence studies with a comparable study design for case finding. This may be
      due to a careful diagnostic evaluation with the use of specified diagnostic
      criteria, excluding patients with other parkinsonian syndromes.

PMID- 8552104
TI  - Striated anal sphincter denervation in patients with progressive supranuclear
      palsy.
AB  - Anal sphincter electromyography may contribute to the differential diagnosis
      between Parkinson's disease (PD) and other parkinsonisms featuring autonomic
      dysfunction, such as multiple system atrophy (MSA). Although patients with
      progressive supranuclear palsy (PSP) do not normally exhibit clinical signs of
      autonomic dysfunction, a few may be first seen with urinary and fecal
      incontinence. We performed an electromyographic study of the anal sphincter in 12
      patients with clinical criteria of probable or definite PSP, two of them with
      clinical manifestations of vesical and anal sphincter dysfunction. The results
      have been compared with those obtained from six patients with PD and six patients
      with MSA. An abnormal anal sphincter examination was present in five of 12 PSP
      patients (41.6%). The abnormal motor units of these patients were
      indistinguishable from those observed in patients with MSA. Patients with MSA had
      the largest, and patients with PD had the lowest, proportion of abnormal motor
      units. We conclude that some patients with PSP may have electromyographic signs
      of denervation in the anal sphincter, which make them indistinguishable by using
      this test alone from patients with MSA.

PMID- 8552105
TI  - Reciprocal inhibition in writer's cramp.
AB  - We studied the inhibition of median H-reflexes by conditioning stimuli on the
      radial nerve in 13 patients with writer's cramp, eight of the simple type and
      five of the dystonic type, and in 14 normal volunteers. The patients and controls
      were right-handed, and their right arms were studied. Asymptomatic left arms were
      also studied in nine of 13 patients. In the control group we identified three
      periods of inhibition, with maximum peaks at conditioning-test intervals of 0 ms
      (41 +/- 17%), 20 ms (40 +/- 13%), and 100 ms (36 +/- 20%). In the patient group,
      the amplitudes of inhibition of these three periods in both arms were
      significantly less than those in the control group. However, there were no
      significant differences in the amplitudes of inhibition of these three periods
      between symptomatic and asymptomatic arms. There were also no significant
      differences between simple and dystonic writer's cramps. Our results indicate
      that the attenuation of reciprocal inhibition was present not only in symptomatic
      arms but also in asymptomatic arms of patients with writer's cramp. The defect of
      reciprocal inhibition in the asymptomatic hand has never been documented. We
      suggest that the preexistent electrophysiological abnormality may provide an
      explanation for the development of hand cramp after shifted writing.

PMID- 8552106
TI  - Speech dysfunction in early Parkinson's disease.
AB  - The purpose of this study is to determine if subjects in the early stages of
      untreated Parkinson's disease (PD) or PD treated with deprenyl alone suffer from
      motor speech abnormalities. Speech defects are common in advanced PD, including
      disturbances of respiration, phonation, and articulation. We studied 12 subjects
      with early PD (Hoehn and Yahr stage < or = 2, mean duration disease 3.2 years)
      who were not taking symptomatic therapy and tested them under two conditions: on
      and off deprenyl. None of the subjects was depressed or demented (Mini Mental
      Status mean 29.9/30; Hamilton Depression Rating mean 2.7/52). All functioned
      independently (Schwab and England Activities of Daily Living mean 93.1/100).
      Acoustic and speech productions were assessed using the DSP Sona-Graph 5500 and
      an evaluation of dysarthria. All 12 had at least two characteristics of
      dysarthria on examination, although 8 were not aware of it. Vocal tremor was
      identified on narrow band spectrogram for four subjects. Deprenyl did not have a
      consistent effect on speech. Ten subjects had no detectable change in speech on
      deprenyl, one was worse, and one was improved.

PMID- 8552107
TI  - No evidence for systemic oxidant stress in Parkinson's or Alzheimer's disease.
AB  - Oxidant stress secondary to dopamine metabolism has been proposed as a pathogenic
      factor in the development of Parkinson's disease. Biochemical abnormalities
      extending beyond the central nervous system have been identified in patients with
      this condition. Previous investigators have found abnormally elevated
      concentrations of the lipid peroxidation product, malondialdehyde, in the plasma
      and serum of patients with Parkinson's disease. We attempted to replicate these
      findings but controlled for other factors that could influence malondialdehyde
      levels. We detected no significant elevations in mean serum malondialdehyde
      concentrations in either levodopa-treated or untreated patients with Parkinson's
      disease, compared to normal controls; similarly, no elevation was found in a
      group of patients with dementia of Alzheimer's type. On the other hand, a group
      of subjects with diabetes mellitus but no neurodegenerative disease had
      significantly elevated mean serum malondialdehyde levels, consistent with
      previous studies of diabetic patients. Autoxidation is one of the two major
      routes by which dopamine and dopa metabolism may generate oxygen free radicals.
      We analyzed the autoxidation product of dopa, 5-S-cysteinyl-dopa, in the plasma
      of these same groups of patients with neurodegenerative disease and normal
      controls; no significant differences were identified. Serum concentrations of two
      other antioxidant substances, alpha-tocopherol and uric acid, were also
      statistically similar in these groups. In conclusion, analysis of several blood
      products relevant to oxidant stress, including malondialdehyde, 5-S-cysteinyl
      dopa, alpha-tocopherol, and uric acid, failed to distinguish patients with
      Parkinson's disease or dementia of Alzheimer's type from controls.

PMID- 8552108
TI  - Botulinum toxin: influence on respiratory heart rate variation.
AB  - Remote adverse effects of local intramuscular botulinum toxin were investigated
      in a prospective follow-up study. Twenty-six patients with spasmodic torticollis
      were examined (18 women, eight men, 45 +/- 13 years). Respiratory heart rate
      variation (HRV) was investigated by a computerized method. Different parameters
      were recorded (beats per minute, coefficient of variation, root mean square
      successive difference (RMSSD), spectral analysis, difference and quotient between
      maximum and minimum RR intervals, mean circular resultant). After one
      intramuscular injection of 12.5 ng botulinum toxin (Porton Products Ltd.,
      England), no significant influence on HRV was seen. After the second injection, a
      significant attenuation was seen of four parameters (coefficient of variation,
      Rmax - Rmin, Rmax divided by Rmin, mean circular resultant) that lasted up to
      several months. No clinically manifest remote side effects and no cardiac
      arrhythmia were seen for several months of botulinum toxin treatment. Our
      investigation proves an effect of local intramuscular botulinum toxin on
      autonomic cardiac innervation.

PMID- 8552109
TI  - Long latency postural reflexes are under supraspinal dopaminergic control.
AB  - Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior
      muscles induced by "toe-up" rotational perturbations is abnormal in standing
      patients with Parkinson's disease. To investigate the contribution of
      dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients
      with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic
      neuroleptic medication (7 with mild parkinsonism), 8 patients with young-onset
      Parkinson's disease, and 4 patients with MPTP-induced parkinsonism. Results were
      compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial
      (predictable) perturbations of 4 degrees amplitude, (b) 10 serial (predictable)
      perturbations of 10 degrees amplitude, and (c) 20 randomly mixed (unpredictable)
      perturbations of either 4 or 10 degrees amplitude. In normal subjects, LL reflex
      amplitudes were adapted to match predictable variations in stimulus size, whereas
      under unpredictable conditions a "default" response emerged that anticipated the
      10 degrees perturbation. LL reflex scaling under predictable conditions was
      intact in patients with neuroleptic-induced parkinsonism and young-onset
      Parkinson's disease, but the large default LL response under unpredictable
      conditions was absent. In patients with MPTP-induced parkinsonism, LL reflex
      scaling was absent during both predictable and unpredictable conditions. We
      conclude that abnormal scaling of posturally stabilizing LL reflexes is related
      to decreased supraspinal dopaminergic influence.

PMID- 8552110
TI  - Ball experiments in 32 acute akinetic catatonic patients: deficits of internal
      initiation and generation of movements.
AB  - We undertook ball experiments in 32 akinetic catatonic patients in order to
      determine specific functional deficits in the motor system in akinetic catatonia.
      Standardized ball experiments (catching, throwing, stopping, kicking) were
      conducted in 32 acute akinetic catatonic patients (23 without neuroleptics on
      admission), diagnosed according to Lohr, Rosebush, and the Diagnostic and
      Statistical Manual of Mental Disorders (3rd ed, revised) on days 0 and 21.
      Additionally, associated psychopathology was evaluated using different scales on
      days 0 and 21: the Global Assessment Scale, the Brief Psychiatric Rating Scale,
      the Hamilton-Anxiety Scale, the scale for the assessment of negative symptoms
      (SANS), and the Simpson scale for extrapyramidal side effects (SEPS).
      Significantly more patients were able to perform more externally guided tasks
      (catching, stopping) than internally guided tasks (throwing, kicking). Patients
      showed significantly more posturing and awkward movements on day 0 than on day
      21. There was a significantly positive correlation between hypokinetic
      extrapyramidal features (SEPS) and negative symptoms with their cognitive
      alterations (SANS) on day 0. The findings suggest a deficit of internal
      initiation, as in parkinsonism, as well as a dysfunction in the generation of
      voluntary movements in akinetic catatonia. We assume an underactivity in the
      dorsolateral prefrontal cortex and the supplementary motor area with consecutive
      down-regulation of the cortical-striatal-thalamic circuit, the "motor loop," in
      catatonia.

PMID- 8552111
TI  - Neurological Wilson's disease studied with magnetic resonance imaging and with
      positron emission tomography using dopaminergic markers.
AB  - Four patients with neurological Wilson's disease were investigated using magnetic
      resonance imaging (MRI) and positron emission tomography (PET). All patients had
      dystonia as their major clinical manifestation but also had dysarthria and at the
      presentation of the disease had choreoathetoid movements in at least one limb. A
      multitracer approach with PET was used to visualize various aspects of
      dopaminergic function; [11C]-(+)-nomifensine (NMF), [11C]raclopride (RAC) and
      [11C]-L-DOPA (one patient). Correlation analysis of RAC and NMF binding as well
      as putamen/caudate uptake ratios showed corresponding reductions. The patient
      investigated with [11C]-L-DOPA had a normal striatal uptake. Generally,
      structural changes as shown by MRI corresponded to reductions both in NMF and RAC
      binding. There was no evident correspondence between PET findings and the
      severity of clinical symptoms seen in the individual patient. In two patients
      with discrete neurological impairment at the time of investigation, PET showed
      serious presynaptic dopaminergic lesions in the putamen. Our data suggest that
      the striatal degeneration seen in Wilson's disease comprises a complex pathology
      involving both afferent and efferent projections. The discrete neurological
      impairment seen in some patients with gross striatal pathology might be due to
      concomitant lesions in functionally counteracting basal ganglia circuits.

PMID- 8552112
TI  - Long-term tolerability and efficacy of cabergoline, a new long-acting dopamine
      agonist, in Parkinson's disease.
AB  - Motor fluctuations constitute a severe complication of chronic levodopa therapy.
      The addition of dopamine agonists may partially alleviate these responses;
      however, due to the short half-life of these drugs, several daily doses are
      required. Cabergoline is a new dopamine agonist with a long half-life and can be
      given in a single daily dose. Seventeen patients with severe fluctuations were
      treated with cabergoline, seven of them for > 1 year (up to 39 months). The motor
      status ameliorated and the percentage of "off" hours significantly decreased in
      the first year and did not increase significantly later during long-term follow
      up. Cabergoline is a promising treatment for parkinsonian patients with motor
      fluctuations.

PMID- 8552113
TI  - Epidemiology and outcome of cervical dystonia (spasmodic torticollis) in
      Rochester, Minnesota.
AB  - The natural history of cervical dystonia (spasmodic torticollis) was investigated
      in a population-based study in Rochester, Minnesota. Eleven new cases were
      identified with onset during the 20-year period 1960-1979. The overall incidence
      rate was 1.2 per 100,000 person-years (95% confidence interval 0.5-1.9) with a
      female:male ratio of age-adjusted incidence rates of 3.6:1. A unitary etiology
      was not apparent: injury antedated onset in four of the 11 patients, whereas six
      had documented thyroid disease and four had diabetes. A family history of
      movement disorder was recorded for only one subject. Only one of the cases would
      have been classified as moderate in severity; the others were mild. In follow-up
      through 1993, progressive disability was noted in only two patients, and two
      others went into remission. Three cases of intracranial aneurysm were confirmed,
      two of which produced fatal subarachnoid hemorrahage. A third death was due to
      amyotrophic lateral sclerosis.

PMID- 8552114
TI  - Effects of selective serotonergic ligands on posthypoxic audiogenic myoclonus.
AB  - Male Sprague-Dawley rats underwent cardiac arrest and resuscitation, subsequently
      exhibiting posthypoxic myoclonus. The audiogenic posthypoxic myoclonus in these
      animals could be attenuated with the following drugs: 5-hydroxytryptophan (5-HTP,
      serotonin [5-HT] precursor), N-(3-trifluoro-methylphenyl)piperazine hydrochloride
      (TFMPP, 5-HT1B/1C/2 agonist), (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrobromide
      (DOI, 5-HT2 agonist), and 1-(m-chlorophenyl)-biguanide hydrochloride (m-CPBG, 5
      HT3 agonist). In contrast, the following drugs were ineffective: (+/-)-8-hydroxy
      dipropylaminotetralin hydrobromide (8-OH-DPAT, 5-HT1A agonist), buspirone
      hydrochloride (5-HT1A agonist), 7-trifluoromethyl-4(4-methyl-l-piperazinyl)
      pyrrolo[1,2- a]quinoxaline maleate (CGS 12066B, 5-HT1B agonist), ketanserin
      tartrate (5-HT2 antagonist), methysergide maleate (5-HT2 antagonist), fluoxetine
      (5-HT uptake blocker), and saline (vehicle). The data suggest that enhancement of
      serotonergic activity, particularly through 5-HT2 and 5-HT3 receptors, have
      therapeutic potential for the treatment of posthypoxic myoclonus.

PMID- 8552115
TI  - Role of peripheral inputs in cerebellar tremor.
AB  - Tremors reflected in the handwriting in nine right-handed male patients with
      right-sided cerebellar lesions were studied by reversibly blocking peripheral
      inputs from the hand. Blocking was achieved by applying a sphygmomanometer cuff
      over the mid-arm and increasing the pressure up to 200 mm Hg. Evoked potentials
      from the ulnar nerve and handwriting were monitored in each subject at periodic
      intervals. Improvement in writing was noticed in 3-5 min in different subjects
      that coincided with partial reduction of the amplitude of the neurograms. This
      reduction is consistent with dissociate conduction in a small population of large
      medullated fibers. On releasing the cuff, the neurograms returned to their normal
      height within the same time frame of 3-5 min, and the handwriting deteriorated
      with return of tremor. No change in the handwriting of the volunteers was
      observed at any stage. The ages of the volunteers ranged from 25 to 48 years and
      those of the patients from 28 to 56 years. The duration of illness of the
      patients ranged from 1 to 8 years.

PMID- 8552116
TI  - The movement-related cortical potential is abnormal in patients with idiopathic
      torsion dystonia.
AB  - Voluntary movements, such as the self-paced finger extension task used in the
      present experiments, are preceded by a slowly rising negative
      electroencephalographic potential [the movement-related cortical potential
      (MRCP)]. The early NS1 component of the potential was no different in patients
      with primary dystonia affecting the arm (n = 6) compared with matched controls.
      In contrast, the peak amplitude of the MRCP was smaller in the patients, despite
      the fact that the movements made by the two groups were very similar; it was of
      equal size over both left and right hemispheres, rather than being larger on the
      side contralateral to the movement. These results are similar to those observed
      by others in patients with symptomatic dystonia secondary to lesions of the basal
      ganglia or their output pathways and may reflect abnormal basal ganglia input to
      motor areas of cortex before the onset of a self-paced movement.

PMID- 8552117
TI  - Toward a better definition of the restless legs syndrome. The International
      Restless Legs Syndrome Study Group.
AB  - A large International Restless Legs Syndrome (RLS) Study Group has been formed.
      As its first task, the group has taken upon itself the role of defining the
      clinical features of the RLS. As minimal criteria for diagnosis, the group
      proposes the following four features: (a) desire to move the extremities, often
      associated with paresthesias/dysesthesias; (b) motor restlessness; (c) worsening
      of symptoms at rest with at least temporary relief by activity, and (d) worsening
      of symptoms in the evening or night. Other features commonly seen in RLS include
      sleep disturbance, periodic limb movements in sleep and similar involuntary
      movements while awake, a normal neurological examination in the idiopathic form,
      a tendency for the symptoms to be worse in middle to older age, and, in some
      cases, a family history suggestive of an autosomal dominant mode of inheritance.

PMID- 8552118
TI  - Screening Parkinson's disease: a validated questionnaire of high specificity and
      sensitivity.
AB  - A questionnaire designed to screen Parkinson's disease (PD) in literate
      populations has been developed. It consists of nine questions, self-administered
      at medical facilities or by mail, and a scale of weights for ascribing scores to
      specific questions when the answer is positive. The questions were chosen to be
      symptom specific for PD and the weights were determined from answers provided by
      37 PD patients in a neurological outpatient clinic. The questionnaire sensitivity
      was tested on a different PD population from the same outpatient clinic--50
      individuals--and the specificity on a group of 100 ophthalmological patients. The
      sensitivity was 100% and the specificity was 100%. Three individuals who screened
      positive among the 100 ophthalmological patients were assessed and given a new
      diagnosis of PD. This questionnaire therefore constitutes an instrument that
      should prove valuable as the first stage of a door-to-door survey. It has high
      sensitivity and specificity.

PMID- 8552119
TI  - Anorectal function in fluctuating (on-off) Parkinson's disease: evaluation by
      combined anorectal manometry and electromyography.
AB  - Anorectal dysfunction and constipation are well recognized in Parkinson's disease
      and may reflect the direct involvement of the gastrointestinal tract by the
      primary Parkinson's disease process. We hypothesized, therefore, that anorectal
      function would alter in parallel with fluctuations in motor function related to
      on- and off-periods in Parkinson's disease, and employed combined anorectal
      manometry and electromyography to investigate anorectal function during both on-
      and off-periods in patients with Parkinson's disease. Manometric recordings
      revealed a deterioration in voluntary sphincter squeeze during off-periods
      (squeeze index, on versus off, mean +/- SEM: 46.4 +/- 11.1 versus 29.6 +/- 7.9 mm
      Hg, p < 0.05); correspondingly, simultaneous electromyographic (EMG) recordings
      showed poor recruitment of external anal sphincter and puborectalis muscles
      during off-periods. A hypercontractile ("paradoxical") rectosphincteric reflex
      response occurred during both on- and off-periods, and was associated with an
      increase in EMG activity in the external sphincter and/or the puborectalis
      muscle. These changes in manometric and EMG parameters paralleled changes in
      overall motor function. These findings provide further support for the
      involvement of the pelvic floor musculature in the Parkinson's disease process
      and also provide EMG correlates for some of the manometric abnormalities
      described in Parkinson's disease.

PMID- 8552120
TI  - Postural finger tremor exhibited by Parkinson patients and age-matched subjects.
AB  - Physiological correlates of postural tremor of the finger seen in Parkinson's
      disease patients are different from those seen in age-matched control subjects. A
      significant correlation between the spectral peak of acceleration and the
      spectral peak of rectified electromyographic activity from the muscle responsible
      for finger extension was found in Parkinson's disease patients. This correlation
      was not seen in age-matched control subjects. Any neural drive imposed on the
      motoneuron pool from supraspinal levels would enhance the electromyographic
      activity. Likewise, any feedback effects via spinal stretch reflexes or
      supraspinal stretch responses would be mediated through the motoneuron pool and
      electromyographic activity. The results of this research support the theory that
      Parkinson tremor is a centrally driven rhythm that may be influenced by feedback
      effects, whereas physiological tremor is due to a complex interaction of central,
      feedback, and mechanical effects.

PMID- 8552121
TI  - A clinical and pharmacokinetic case study of an interaction of levodopa and
      antituberculous therapy in Parkinson's disease.
AB  - We studied the relationship between levodopa response and antituberculous
      treatment in a patient with idiopathic Parkinson's disease whose parkinsonism
      deteriorated when treatment with rifampicin and isoniazid (Rifinah) for pulmonary
      tuberculosis was started. A levodopa challenge test with regular recording of
      motor function was performed during, and again after stopping, antituberculous
      treatment. Plasma levodopa and levodopa metabolite pharmacokinetic profiles were
      determined using standard techniques. "On" period duration was 75% longer after
      antituberculous treatment had been stopped. These clinical findings correlated
      with a 37% increase in area under the concentration versus time curve (AUC), a
      103% increase in apparent elimination half-life (t1/2), a 41% increase in time to
      maximum concentration (Tmax), and a 33% decrease in maximum concentration (Cmax)
      of levodopa. A concurrent increase in plasma 3-O-methyldopa (3-OMD) and a
      decrease in plasma 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid
      (HVA), the three major metabolites of levodopa, suggests an inhibition of the
      enzyme dopa decarboxylase, probably by isoniazid.

PMID- 8552122
TI  - A "combined" levodopa test as a useful method for evaluating the efficacy of
      dopamine agonists: application to pergolide and bromocriptine.
AB  - The efficacy of pergolide as adjunct to levodopa therapy was compared to that of
      bromocriptine in 12 parkinsonian patients with fluctuating motor disability and
      levodopa-induced dyskinesias (mean age of onset, 50.6 +/- 8 years; Hoehn and Yahr
      stage between II and IV; mean basal UPDRS motor score, 30.6 +/- 8.6), in a double
      blind crossover study. After an 8-day habituation to each agonist, an acute
      challenge of a supraliminal dose of levodopa ("levodopa test") was performed in
      association with either 1 mg pergolide or 10 mg bromocriptine. The delay to onset
      and the duration of therapeutic benefit, the percentage improvement in motor
      disability, and the severity of onset and peak-dose dyskinesias were evaluated.
      Both agonists significantly increased the duration of therapeutic benefit, but
      pergolide more so than bromocriptine (p = 0.02). Pergolide also tended to reduce
      the severity of dyskinesias and was globally perceived by the patients to be more
      efficacious than bromocriptine on parkinsonian symptoms and fluctuations. This
      study illustrated the usefulness of the "levodopa test" in evaluating,
      objectively, the effects of dopamine agonists.

PMID- 8552123
TI  - Bilateral subthalamic nucleus stimulation for severe Parkinson's disease.
AB  - Subthalamic nucleus (STN) lesions or high-frequency stimulations could improve
      parkinsonian symptoms in monkeys treated by MPTP. We have applied the procedure
      of chronic stimulation to the STN in severely disabled parkinsonian patients.
      This article presents the case of the first patient operated on bilaterally.
      Bilateral STN stimulation has greatly improved akinesia and rigidity. The benefit
      was maintained < or = 15 months after surgery. Unilateral stimulation induced
      motor effects mainly in contralateral limbs. Further studies are needed to
      evaluate the value of this procedure in the treatment of Parkinson's disease.

PMID- 8552124
TI  - Intrathecal baclofen for motor disorders.
AB  - To test the efficacy of intrathecal baclofen in various movement disorders, 18
      patients with dystonia, head trauma, cerebral palsy, rigidity, or painful spasms
      underwent a trial of intrathecal baclofen. Ten went on to permanent implantation
      with an infusion pump to provide long-term treatment. Patients with a component
      of spasticity, painful spasms, or focal dystonias did best, and no response was
      seen in patients with rigidity due to anoxic encephalopathy. A videotape of
      responses is provided.

PMID- 8552125
TI  - Are death certificates reliable to estimate the incidence of Parkinson's disease?

PMID- 8552126
TI  - Fentanyl-induced dyskinesias.

PMID- 8552127
TI  - Botulinum toxin A is effective in treating trismus associated with postradiation
      myokymia and muscle spasm.

PMID- 8552128
TI  - Temporary worsening of parkinsonism in a patient with Parkinson's disease after
      treatment with paclitaxel for a metastatic grade IV adenocarcinoma.

PMID- 8552129
TI  - Sertraline-induced exacerbation of tics in Tourette's syndrome.

PMID- 8552130
TI  - Treatment of superficial siderosis of the central nervous system.

PMID- 8552131
TI  - Apraxia of lid opening.

PMID- 8552132
TI  - Genotoxic effects produced by capsaicin in mouse during subchronic treatment.
AB  - Capsaicin is the chemical responsible for the pungent, hot properties of
      Capsicum, a vegetable widely consumed in the diet of many countries in the world.
      In this work, the genotoxic capacity of capsaicin was studied in mouse during a
      32-day treatment. We used the dosages of 1.46 and 1.94 mg/kg given by the i.p.
      route. Each week, the frequency of micronucleated normochromatic erythrocytes (MN
      NE) and the ratio polychromatic/normochromatic erythrocytes (PE/NE) were scored.
      At the end of the experiment we also scored the frequency of sister chromatid
      exchanges (SCE). The results in the MN-NE analysis showed a genotoxic response
      with 1.94 mg/kg starting from day 16, while the 1.46 mg/kg dose produced a
      significant increase of MN-NE only at the 32nd day. The ratio PE/NE was only
      affected at the 32nd day with the high dose. Concerning the SCE frequency, the
      genotoxic effect was only observed with the highest dose. These results indicated
      that capsaicin is a genotoxicant, and due to the probable relation between an
      excessive consumption of Capsacum and an increase in gastric cancer, it is
      suggested that its consumption could be moderated until a definitive risk for
      humans is established.

PMID- 8552133
TI  - Genotoxic evaluation of three heterocyclic N-methylcarbamate pesticides using the
      mouse bone marrow micronucleus assay and the Saccharomyces cerevisiae strains D7
      and D61.M.
AB  - The carbamate insecticides benfuracarb, carbosulfan and furathiocarb were
      investigated in the mouse bone marrow micronucleus assay to establish whether
      they show cytogenetic activity in vivo. Two doses of each substance were
      administered intraperitoneally to NMRI mice. All of the three substances led to a
      positive micronucleus response in polychromatic erythrocytes of the bone marrow
      at different expression times. While furathiocarb and carbosulfan showed similar
      patterns of the time-dependence of the micronucleus formation with maximum values
      after 72 h, benfuracarb exhibited a different behaviour with the maximum increase
      taking place within 24 h after substance application. In furathiocarb-treated
      animals the ratio of normochromatic to polychromatic erythrocytes showed a dose
      and time depending increase with the highest value obtained after 72 h in animals
      treated with the upper dose. The two yeast test systems Saccharomyces cerevisiae
      strains D7 and D61.M were applied in order to evaluate the genetic endpoints gene
      mutation, gene conversion and aneuploidy induction. None of the three
      insecticides had an influence on the frequencies of gene conversion and reverse
      mutation in the yeast S. cerevisiae D7 when tested with and without metabolic
      activation. In strain D61.M however benfuracarb and furathiocarb led to an
      increase of chromosome loss in the presence of the S9 metabolizing system.

PMID- 8552134
TI  - Inhibitory effect of hemin, chlorophyllin and related pyrrole pigments on the
      mutagenicity of benzo[a]pyrene and its metabolites.
AB  - Hemin and chlorophyllin are known to inhibit strongly the mutagenicity of
      benzo[a]pyrene in the Salmonella assay. To further investigate this phenomenon, a
      series of these pyrrole pigments including pure samples of Cu- and Fe-chlorins
      were tested for their potency to inhibit the mutagenicity of benzo[a]pyrene and
      its metabolites, benzo[a]pyrene-7,8-diol, benzo[a]pyrene-4,5-epoxide, and
      benzo[a]pyrene-7,8-diol-9,10-epoxide. Hemin was the most potent among the
      pigments tested for these inhibitions. Both hemin and Cu-chlorin accelerated
      efficiently the degradation of benzo[a]pyrene-7,8-diol-9,10-epoxide, and this
      acceleration seemed to be the predominant mechanism by which these pigments
      inhibit the overall mutagenicity of benzo[a]pyrene in Salmonella. Based on
      spectroscopic evidence, we speculate that a complex formation between hemin and
      benzo[a]pyrene-7,8-diol-9,10-epoxide takes place and that this complexing is the
      cause of the accelerated degradation.

PMID- 8552135
TI  - A miniaturized Ames mutagenicity assay employing bioluminescent strains of
      Salmonella typhimurium.
AB  - Increased awareness of the role of environmental factors in carcinogenesis has
      led to an emphasis on preventing or minimizing exposure to genotoxicants. This is
      presently promoting the development of simple, rapid, cost-effective mutagenicity
      screening assays. We have developed a test system based on the well-known
      Salmonella mutagenicity assay. The lux genes, which permit cells to emit light
      through bioluminescence, were introduced into Salmonella typhimurium strain TA98.
      These bacteria were exposed for 48 h to chemicals or complex mixtures in 48-well
      microplates containing an appropriate liquid medium. Cells were subsequently
      centrifuged and resuspended in buffer. The final postexposure revertant biomass
      was then estimated using a microluminometer. Replication trials confirmed
      methodological reproducibility. Clear dose-response relationships were obtained
      with the direct frameshift mutagens 4NQO and 2NF. Mutagenicity threshold effect
      concentrations found for these compounds were comparable to those reported in the
      literature. Industrial effluents and environmental extracts (effluents, suspended
      solids) were also tested and results compared well with those of the SOS
      Chromotest. While further validation of this new adaptation of the Ames test will
      be required, it appears at this time that it could be well suited for routine
      screening of xenobiotics and environmental samples.

PMID- 8552136
TI  - In vivo radioprotection with garlic extract.
AB  - Garlic extract was evaluated in the mouse bone marrow micronucleus test for its
      possible protective effects against gamma-radiation-induced chromosomal damage.
      Together with this, biochemical assays were carried out to determine the changes
      in sulfhydryl content and glutathione S-transferase activities. Three doses of
      freshly prepared garlic extract (125, 250 and 500 mg/kg b.w.) were orally
      administered for 5 consecutive days, and the animals were irradiated 2 h after
      the final feeding. The results of the micronucleus test demonstrated that pre
      treatment with garlic extract can lead to significant dose-related reductions in
      the frequencies of gamma-radiation-induced (2 Gy) micronucleated polychromatic
      erythrocytes. The anticlastogenic effect of garlic extract was observed against
      lower radiation doses of 0.5 and 1 Gy, but not 0.25 Gy. Significant increases in
      the sulfhydryl content and glutathione S-transferase activity were observed after
      either pre-treatment with garlic extract or irradiation. However, the irradiated
      garlic-extract pre-treated animals showed a significant reduction in sulfhydryl
      content and glutathione S-transferase activities.

PMID- 8552137
TI  - Mutagenicity of soy sauce treated with nitrite in the presence of ethanol or
      alcoholic beverages.
AB  - The mutagenicity induced by soy sauce after reaction with 50 mM nitrite at pH 3,
      37 degrees C, for 60 min in the presence of 1.25-10% ethanol was reduced in
      proportion to the ethanol concentration. The mutagenicity of soy sauce treated
      with nitrite was also reduced in the presence of commercial alcoholic beverages,
      Japanese sake, wine, 'shochu', whiskey and brandy, but not beer, in proportion to
      the concentration. The mutagenicity of nitrite-treated tyramine, which is a major
      precursor of a mutagen in soy sauce treated with nitrite, was strongly reduced in
      the presence of ethanol, n-propanol or isopropanol and more strongly reduced in
      the presence of methanol, but was increased twofold in the presence of the sugars
      glucose or sucrose. The reduction of the mutagenicity of nitrite-treated tyramine
      required simultaneous treatment of tyramine with ethanol and nitrite. The
      mutagenicity of tyramine treated with nitrite was clearly reduced in the presence
      of shochu and whiskey, similarly to ethanol. Analysis by high-performance liquid
      chromatography revealed that the reduction of the mutagenicity of nitrite-treated
      tyramine in the presence of ethanol resulted from the reduced production of
      mutagenic 3-diazotyramine from tyramine.

PMID- 8552138
TI  - Dominant lethal and heritable translocation tests with chlorambucil and melphalan
      in male mice.
AB  - Chemicals used in the treatment of cancer include several that are potent
      mutagens in a range of in vitro and in vivo assays. For some, genetic effects
      have also been demonstrated in humans, detected as chromosomal aberrations in
      peripheral lymphocytes. Because (1) many of these agents are confirmed mutagens,
      (2) humans are exposed to them in relatively high doses, and (3) an increasing
      number of early cancer victims are surviving to reproductive age, it is important
      that information be available on the genetic and reproductive hazards associated
      with exposure to these agents. Chlorambucil and melphalan are structurally
      related chemicals that are included in our efforts to identify and assess such
      hazards among cancer chemotherapy agents. To date, both have been reported to
      induce specific locus mutations in germ cells of male mice (Russell et al., 1989;
      Russel et al., 1992b) and melphalan is one of very few chemicals shown to induce
      such mutations in spermatogonial stem cells. More recently, both chemicals were
      found to have strong reproductive effects in female mice (Bishop and Generoso,
      1995, in preparation). In the present studies, these chemicals were tested for
      the induction of dominant lethal mutations and heritable translocations in male
      mice. Both chemicals were found to have reproductive effects attributable to
      cytotoxicity in specific male germ cell stages and to induce dominant lethal
      mutations and heritable translocations in postmeiotic germ cells, particularly in
      mid to early stage spermatids. Thus, relatively extensive data are now available
      for assessing the genetic and reproductive hazards that may result from
      therapeutic exposures to these chemicals.

PMID- 8552139
TI  - DNA adducts and P450 induction in human, rat and avian liver cells after exposure
      to polychlorobiphenyls.
AB  - Polychlorinated biphenyls (PCBs) are industrial chemicals which have been
      detected in fish, birds and humans. They are known to exert marked effects on the
      liver. They induce hepatocellular carcinoma in rats and birds, and are suspected
      of being carcinogenic to humans. To better understand the genotoxic effects of
      PCBs, we used 32P-postlabelling to investigate DNA adduct formation, after
      exposure to PCBs (Aroclor 1254 and 3,3',4,4'-tetrachlorobiphenyl), in primary
      cultures of fetal hepatocytes from two animal species and in a human cell line
      (Hep G2). We also studied the induction of 7-ethoxyresorufin-O-deethylase (EROD)
      in these PCB-treated cells. The three cell types used are known to express
      different cytochrome P450 families. The aim was to see whether a correlation
      could be established between EROD activity (a CYP1A1-related activity) and DNA
      adduct formation. DNA adducts were found in all three models after exposure to 50
      microM 3,3',4,4'-tetrachlorobiphenyl. The number of adducts was higher in quail
      hepatocytes (37 adducts per 10(9) nucleotides) than in rat hepatocytes or Hep G2
      cells (20 adducts per 10(9) nucleotides in both cases). The major adduct was the
      same in all three cell types, but some adducts were found in only one or two
      species. These inter-species differences probably reflect metabolic differences
      leading to different ultimate carcinogens. Exposure to Aroclor 1254 failed to
      produce significant levels of DNA adducts, suggesting that pre-treated cells are
      required to magnify Aroclor 1254 metabolism. No correlation was found between
      adduct formation and the level of EROD induction.

PMID- 8552140
TI  - Ethanol-induced single-strand DNA breaks in rat brain cells.
AB  - Male Sprague-Dawley rats were intubated with 4 g/kg body weight of ethanol (in a
      20%, v/v, water solution). Brain cells were analyzed for single-strand DNA breaks
      at various post-ethanol administration time points using an alkaline microgel
      electrophoresis assay. Results showed a significant increase in single-strand DNA
      breaks in brain cells that peaked at approx. 4 h and returned to control level
      within 6 h after ethanol administration.

PMID- 8552141
TI  - Comparison of the microgel electrophoresis assay and other assays for
      genotoxicity in the detection of DNA damage.
AB  - Genotoxic agents can be detected by measuring DNA damage which result in the
      migration of DNA from single cells in agarose, using an electrophoretic field
      under alkaline conditions. The alkaline microgel electrophoresis technique was
      compared with in vitro structural chromosomal aberration (SCA) and mutation
      assays using V79 Chinese hamster lung cells and in vivo assays such as the bone
      marrow micronucleus assay in mice and a hepatocyte DNA repair assay in rats.
      Genotoxicants tested were those routinely used as positive control compounds in
      the various assays. In vitro assays included liver S9 for metabolic activation of
      cyclophosphamide (CP) for the SCA assay and benzo[a]pyrene (BP) for the mutation
      assay. A highly significant increase in DNA migration was induced by these agents
      under circumstances where a significant increase in DNA damage was detected using
      other endpoints. The alkaline microgel electrophoresis assay thus demonstrated
      the ability to detect DNA damage coinciding with the induction of DNA damage
      detected in these other assays for genotoxicity.

PMID- 8552142
TI  - Sudden cardiac death triggered by an earthquake.
AB  - BACKGROUND: The earthquake that struck the Los Angeles area at 4:31 a.m. on
      January 17, 1994, was one of the strongest earthquakes ever recorded in a major
      city in North America. Once the life-threatening situation was over, the
      Northridge earthquake, so called because its epicenter was near Northridge,
      California, just north of Los Angeles, provided investigators an unusual
      opportunity to examine the relation between emotional stress and sudden cardiac
      death. METHODS: We reviewed the records of the Department of Coroner of Los
      Angeles County for the week before the earthquake, the day of the earthquake, the
      six days after the earthquake, and corresponding control periods in 1991, 1992,
      and 1993. RESULTS: On the day of the earthquake, there was a sharp increase in
      the number of sudden deaths from cardiac causes that were related to
      atherosclerotic cardiovascular disease, from a daily average (+/- SD) of 4.6 +/-
      2.1 in the preceding week to 24 on the day of the earthquake (z = 4.41, P <
      0.001). Sixteen victims of sudden death had symptoms, usually chest pain, or died
      within the first hour after the initial tremor. Only three sudden deaths occurred
      during or immediately after unusual physical exertion. During the six days after
      the earthquake, the number of sudden deaths declined to below the base-line
      value, to an average of 2.7 +/- 1.2 per day. CONCLUSIONS: The Northridge
      earthquake was a significant trigger of sudden death due to cardiac causes,
      independently of physical exertion. This finding, along with the unusually low
      incidence of such deaths in the week after the earthquake, suggests that
      emotional stress may precipitate cardiac events in people who are predisposed to
      such events.

PMID- 8552143
TI  - The intensity of hemodialysis and the response to erythropoietin in patients with
      end-stage renal disease.
AB  - BACKGROUND: Anemia (characterized by a hematocrit of 30 percent or lower)
      persists in 40 to 60 percent of patients treated for end-stage renal disease with
      maintenance hemodialysis, despite concomitant erythropoietin (epoetin) therapy.
      We tested the hypothesis that inadequate dialysis is a key reason for the
      insufficient response to erythropoietin in patients with end-stage renal disease
      who are receiving hemodialysis. METHODS: We prospectively studied 135 randomly
      selected patients undergoing hemodialysis who had been receiving intravenous
      erythropoietin for at least four months. The adequacy of dialysis was assessed by
      measuring the percent reduction in the blood urea nitrogen concentration and the
      serum albumin concentration. The hematocrit was measured weekly for four weeks,
      transferrin saturation was measured, and coexisting illnesses were documented. To
      determine the effect of an increased level of dialysis on the hematocrit, the
      thrice-weekly schedule of dialysis was increased to raise the mean urea-reduction
      value from 60.7 to 72 percent for six weeks in 20 consecutive patients whose base
      line urea-reduction value was less than 65 percent. The change in the hematocrit
      in these patients was compared with that observed in the next 20 patients who had
      an equivalent base-line urea-reduction value but whose level of dialysis was not
      altered. RESULTS: The mean hematocrit of the entire group was 29.2 +/- 4 percent,
      and the mean thrice-weekly dose of erythropoietin was 59 +/- 29 U per kilogram of
      body weight. The mean serum albumin concentration was 3.8 +/- 0.4 g per
      deciliter, the mean urea-reduction value was 62 +/- 4.8 percent, and the mean
      transferrin saturation was 20 +/- 9 percent. Multiple regression analysis
      revealed direct correlations between the hematocrit and the serum albumin
      concentration (P = 0.009) and between the hematocrit and the urea-reduction value
      (P = 0.012) after adjustment for other factors. A logistic-regression analysis
      indicated that an 11 percent increase in the urea-reduction value doubled the
      odds that a patient would have a hematocrit above 30 percent. After six weeks of
      increased intensity of dialysis in 20 patients with base-line urea-reduction
      values of less than 65 percent, the mean (+/- SE) hematocrit rose from 28.4 +/-
      0.78 percent to 32.3 +/- 0.71 percent (P = 0.002); there was no significant
      change in a control group of 20 patients with equivalent base-line urea-reduction
      values in whom the dialysis level was not altered (28.2 +/- 0.84 percent to 26.3
      +/- 0.85 percent; P = 0.175). CONCLUSIONS: In patients with end-stage renal
      disease, inadequate hemodialysis is associated with a suboptimal response to
      erythropoietin therapy. Increasing the intensity of dialysis in patients with
      anemia who are receiving inadequate dialysis results in a significant increase in
      the hematocrit.

PMID- 8552144
TI  - Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of
      progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS.
AB  - BACKGROUND: Clinical trials of antiretroviral drugs can take years to complete
      because the outcomes measured are progression to the acquired immunodeficiency
      syndrome (AIDS) or death. Trials could be accelerated by the use of end points
      such as changes in CD4+ lymphocyte counts and plasma levels of human
      immunodeficiency virus type 1 (HIV-1) RNA and beta 2-microglobulin, but there is
      uncertainty about whether these surrogate measures are valid predictors of
      disease progression. METHODS: We analyzed data from the Veterans Affairs
      Cooperative Study on AIDS, which compared immediate with deferred zidovudine
      therapy. Patients' plasma levels of HIV-1 RNA and beta 2-microglobulin were
      measured in stored plasma. RESULTS: Among the 129 patients in the immediate
      treatment group, 34 had disease that progressed to AIDS, as compared with 57 of
      the 141 patients in the deferred-treatment group (P = 0.03). Progression to AIDS
      correlated strongly with base-line CD4+ lymphocyte counts (P = 0.001) and plasma
      levels of HIV-1 RNA (P < 0.001), but not with base-line levels of beta 2
      microglobulin (P = 0.14). A decrease of at least 75 percent in the plasma level
      of HIV-1 RNA over the first six months of zidovudine therapy accounted for 59
      percent of the benefit of treatment, defined as the absence of progression to
      AIDS (95 percent confidence interval, 13 to 112 percent). Plasma beta 2
      microglobulin levels and CD4+ lymphocyte counts explained less of the effect of
      treatment. A 75 percent decrease in the plasma HIV-1 RNA level plus a 10 percent
      increase in the CD4+ lymphocyte count could explain 79 percent of the treatment
      effect (95 percent confidence interval, 27 to 145 percent). CONCLUSIONS:
      Treatment-induced changes in the plasma HIV-1 RNA level and the CD4+ lymphocyte
      count, taken together, are valid predictors of the clinical progression of HIV
      related disease and can be used to assess the efficacy of zidovudine and possibly
      other antiretroviral drugs as well.

PMID- 8552145
TI  - Brief report: short stature caused by a mutant growth hormone.

PMID- 8552146
TI  - Images in clinical medicine. Seasonal hemolysis due to cold-agglutinin syndrome.

PMID- 8552147
TI  - A medical disaster response to reduce immediate mortality after an earthquake.

PMID- 8552148
TI  - The management of gout.
AB  - We now have sufficient knowledge to be able to identify the factors contributing
      to hyperuricemia in most patients with gout. Some of these factors, such as
      obesity, a high-purine diet, regular alcohol consumption, and diuretic therapy,
      may be correctable. In patients with persistent hyperuricemia, regular medication
      should lower the serum urate concentration to an optimal level. The continuing
      challenge is to educate patients about correctable factors and the importance of
      regular medication and ensure their compliance so that attacks of gout do not
      recur.

PMID- 8552149
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 5-1996. A 25-year-old man with hemopericardium, bilateral
      hemothorax, and hemoptysis after chest trauma.

PMID- 8552150
TI  - Triggering of sudden death--lessons from an earthquake.

PMID- 8552151
TI  - Anemia, dialysis, and dollars.

PMID- 8552152
TI  - Short stature due to genetic defects affecting growth hormone activity.

PMID- 8552153
TI  - Presidential health.

PMID- 8552154
TI  - Presidential health.

PMID- 8552155
TI  - Presidential health.

PMID- 8552156
TI  - Presidential health.

PMID- 8552157
TI  - Presidential health.

PMID- 8552158
TI  - Familial melanoma and pancreatic cancer. Ligurian Skin Tumor Study Group.

PMID- 8552159
TI  - Familial melanoma and pancreatic cancer.

PMID- 8552160
TI  - Familial melanoma and pancreatic cancer.

PMID- 8552161
TI  - Chronic lymphocytic leukemia.

PMID- 8552162
TI  - Chronic lymphocytic leukemia.

PMID- 8552163
TI  - Association of interleukin-6 and hypoaldosteronism in patients with cancer.

PMID- 8552164
TI  - Treatment of Helicobacter pylori infection in peptic ulcer disease.

PMID- 8552165
TI  - Chemical keratoconjunctivitis from a "foam party".

PMID- 8552166
TI  - Budget politics jeopardizes US drugs credit.

PMID- 8552167
TI  - International papers register decline.

PMID- 8552168
TI  - Bioethics panels may be threat to public debate on research.

PMID- 8552169
TI  - Confidentiality of referees.

PMID- 8552170
TI  - Family likeness.

PMID- 8552171
TI  - The enemy of science is within.

PMID- 8552172
TI  - The enemy of science is within.

PMID- 8552173
TI  - The enemy of science is within.

PMID- 8552174
TI  - The enemy of science is within.

PMID- 8552175
TI  - Biological anthropology.

PMID- 8552176
TI  - Write to reply.

PMID- 8552177
TI  - Austrian science.

PMID- 8552178
TI  - Ethics of genomic patenting.

PMID- 8552179
TI  - Melatonin hype hard to swallow.
AB  - Melatonin is being touted as the latest cure-all. But in their eagerness to
      explain to the public the possible health benefits of this natural hormone, the
      mass media as well as some scientists have misrepresented the scientific data.

PMID- 8552180
TI  - The G-protein nanomachine.

PMID- 8552181
TI  - Taxonomy. Where do rabbits and kin fit in?

PMID- 8552182
TI  - Photobiology. Wrinkles waiting for GoDoT.

PMID- 8552183
TI  - Lateral proton diffusion.

PMID- 8552184
TI  - The 2.0 A crystal structure of a heterotrimeric G protein.
AB  - The structure of a heterotrimeric G protein reveals the mechanism of the
      nucleotide-dependent engagement of the alpha and beta gamma subunits that
      regulates their interaction with receptor and effector molecules. The interaction
      involves two distinct interfaces and dramatically alters the conformation of the
      alpha but not of the beta gamma subunits. The location of the known sites for
      post-translational modification and receptor coupling suggest a plausible
      orientation with respect to the membrane surface and an activated heptahelical
      receptor.

PMID- 8552185
TI  - Cationic cyclopropanation by antibody catalysis.
AB  - Reactions involving highly reactive carbocations play a central role in many
      important chemical processes, such as cyclization reactions. However, the
      potential for controlling the pathways of such reactions to obtain energetically
      disfavoured (but desirable) products has been hard to realize because of the
      difficulties inherent in controlling the conformation and chemical environment of
      the carbocation intermediates. Antibody catalysts, with their high specificity
      and binding energies, can provide the degree of conformational and chemical
      control necessary for directing such reactions. Here we show how antibody
      catalysis can guide cationic cyclization reactions selectively to form products
      (in high yield) that would otherwise be highly disfavoured. Most notable is the
      formation of a strained bicyclic compound containing a rare cyclopropane group.
      To explain our results, we propose a common reaction scheme in which the key step
      is the formation of a highly reactive protonated cyclopropane intermediate;
      subtle structural modifications to the substrate (the compound on which the
      catalytic antibody acts) lead to dramatic differences in the structure of the
      final product.

PMID- 8552186
TI  - Phylogenetic position of the order Lagomorpha (rabbits, hares and allies)
AB  - Ever since they have been classified as ruminants in the Old Testament (Leviticus
      11:6, Deuteronomy 14:7) and equated with hyraxes in the vulgate Latin
      translation, rabbits and their relatives (order Lagomorpha) have frequently
      experienced radical changes in taxonomic rank. By using 91 orthologous protein
      sequences, we have attempted to answer the classical question "What, if anything,
      is a rabbit?". Here we show that Lagomorpha is significantly more closely related
      to Primates and Scandentia (tree shrews) than it is to rodents. This newly
      determined phylogenetic position invalidates the superordinal taxon Glires
      (Lagomorpha + Rodentia), and indicates that the morphological 'synapomorphies'
      previously used to cluster rodents and lagomorphs into Glires, may actually
      represent symplesiomorphies or homoplasies that are of no phylogenetic value.
      This raises the possibility that the ancestral eutherian morphotype may have
      possessed many rodent-like morphological characters.

PMID- 8552187
TI  - Molecular basis of sun-induced premature skin ageing and retinoid antagonism.
AB  - Damage to skin collagen and elastin (extracellular matrix) is the hallmark of
      long-term exposure to solar ultraviolet irradiation, and is believed to be
      responsible for the wrinkled appearance of sun-exposed skin. We report here that
      matrix-degrading metalloproteinase messenger RNAs, proteins and activities are
      induced in human skin in vivo within hours of exposure to ultraviolet-B
      irradiation (UVB). Induction of metalloproteinase proteins and activities
      occurred at UVB doses well below those that cause skin reddening. Within minutes,
      low-dose UVB upregulated the transcription factors AP-1 and NF-kappa B, which are
      known to be stimulators of metalloproteinase genes. All-trans retinoic acid,
      which transrepresses AP-1 (ref. 8), applied before irradiation with UVB,
      substantially reduced AP-1 and metalloproteinase induction. We propose that
      elevated metalloproteinases, resulting from activation of AP-1 and NF-kappa B by
      low-dose solar irradiation, degrade collagen and elastin in skin. Such damage, if
      imperfectly repaired, would result in solar scars, which through accumulation
      from a lifetime of repeated low-dose sunlight exposure could cause premature skin
      ageing (photoageing).

PMID- 8552188
TI  - Normal host prion protein necessary for scrapie-induced neurotoxicity.
AB  - Accumulation of the prion protein PrPSc, a pathological and protease-resistant
      isoform of the normal host protein PrPC, is a feature of prion disease such as
      scrapie. It is still unknown whether scrapie pathology comes about by
      neurotoxicity of PrPSc, acute depletion of PrPC, or some other mechanism. Here we
      investigate this question by grafting neural tissue overexpressing PrPC into the
      brain of PrP-deficient mice which are scrapie-resistant and do not propagate
      infectivity. After intracerebral inoculation with scrapie prions, the grafts
      accumulated high levels of PrPSc and infectivity and developed the severe
      histopathological changes characteristic of scrapie. Moreover, substantial
      amounts of graft-derived PrPSc migrated into the host brain. Even 16 months after
      inoculation no pathological changes were seen in PrP-deficient tissue, not even
      in the immediate vicinity of the grafts. Therefore, in addition to being
      resistant to scrapie infection, brain tissue devoid of PrPC is not damaged by
      exogenous PrPSc.

PMID- 8552189
TI  - Treatment of experimental encephalomyelitis with a peptide analogue of myelin
      basic protein.
AB  - Following induction of experimental encephalomyelitis with a T-cell clone, L10C1,
      that is specific for the myelin basic protein epitope p87-99, the inflammatory
      infiltrate in the central nervous system contains a diverse collection of T cells
      with heterogeneous receptors. We show here that when clone L10C1 is tolerized in
      vivo with an analogue of p87-99, established paralysis is reversed, inflammatory
      infiltrates regress, and the heterogeneous T-cell infiltrate disappears from the
      brain, with only the T-cell clones that incited disease remaining in the original
      lesions. We found that antibody raised against interleukin-4 reversed the
      tolerance induced by the altered peptide ligand. Treatment with this altered
      peptide ligand selectively silences pathogenic T cells and actively signals for
      the efflux of other T cells recruited to the site of disease as a result of the
      production of interleukin-4 and the reduction of tumour-necrosis factor-alpha in
      the lesion.

PMID- 8552190
TI  - Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice.
AB  - Despite its widespread distribution on both lymphoid and myeloid cells, the
      biological role of the low-affinity immunoglobulin-G receptor, Fc gamma RII, is
      not fully understood. Defects in this receptor or its signalling pathway in B
      cells result in perturbations in immune-complex-mediated feedback inhibition of
      antibody production. We now report that Fc gamma RII-deficient animals display
      elevated immunoglobulin levels in response to both thymus-dependent and thymus
      independent antigens. Additionally, the effector arm of the allergic response is
      perturbed in these mice. Mast cells from Fc gamma RII-/- are highly sensitive to
      IgG-triggered degranulation, in contrast to their wild-type counterparts. Fc
      gamma RII-deficient mice demonstrate an enhanced passive cutaneous analphylaxis
      reaction, the result of a decreased threshold for mast-cell activation by Fc
      gamma RIII cross-linking. These results demonstrate that Fc gamma RII acts as a
      general negative regulator of immune-complex-triggered activation in vivo for
      both the afferent and efferent limbs of the immune response. Exploiting this
      property offers new therapeutic opportunities for the treatment of allergic and
      autoimmune disorders.

PMID- 8552191
TI  - Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP
      genes.
AB  - Dysregulation of apoptosis can result in inappropriate suppression of cell death,
      as occurs in the development of some cancers, or in failure to control the extent
      of cell death, as is believed to occur in acquired immunodeficiency and certain
      neurodegenerative disorders, such as spinal muscular atrophy (SMA). Recently, we
      isolated a candidate gene, encoding neuronal apoptosis inhibitor protein (NAIP),
      for SMA. This gene is homologous to two baculovirus inhibitor of apoptosis
      proteins (Cp-IAP and Op-IAP) and is partly deleted in individuals with type I
      SMA. A second SMA candidate gene encoding survival motor neuron (SMN), which is
      contiguous with the NAIP locus on 5q13.1, was also reported. Here we demonstrate
      a NAIP-mediated inhibition of apoptosis induced by a variety of signals, and have
      identified three additional human complementary DNAs and a Drosophila
      melanogaster sequence that are also homologous to the baculovirus IAPs. The four
      open reading frames (ORFs) possess three baculoviral inhibition of apoptosis
      protein repeat (BIR) domains and a carboxy-terminal RING zinc-finger. The human
      iap genes have a distinct but overlapping pattern of expression in fetal and
      adult tissues. These proteins significantly increase the number of known
      apoptotic suppressors.

PMID- 8552192
TI  - A presynaptic inositol-5-phosphatase.
AB  - Synaptojanin is a nerve terminal protein of relative molecular mass 145,000 which
      appears to participate with dynamin in synaptic vesicle recycling. The central
      region of synaptojanin defines it as a member of the inositol-5-phosphatase
      family, which includes the product of the gene that is defective in the
      oculocerebrorenal syndrome of Lowe. Synaptojanin has 5-phosphatase activity and
      its amino-terminal domain is homologous with the yeast protein Sac1 (Rsd1), which
      is genetically implicated in phospholipid metabolism and in the function of the
      actin cytoskeleton. The carboxy terminus, which is of different lengths in adult
      and developing neurons owing to the alternative use of two termination sites, is
      proline-rich, consistent with the reported interaction of synaptojanin with the
      SH3 domains of Grb2 (refs 1, 2). Synaptojanin is the only other major brain
      protein besides dynamin that binds the SH3 domain of amphiphysin, a presynaptic
      protein with a putative function in endocytosis. Our results suggest a link
      between phosphoinositide metabolism and synaptic vesicle recycling.

PMID- 8552193
TI  - Role for a Xenopus Orc2-related protein in controlling DNA replication.
AB  - The six-subunit origin recognition complex (ORC) is essential for the initiation
      of DNA replication at specific origins in the budding yeast Saccharomyces
      cerevisiae. An important issue is whether DNA replication in higher eukaryotes,
      in which the characteristics of replication origins are poorly defined, occurs by
      an ORC-dependent mechanism. We have identified a Xenopus laevis Orc2-related
      protein (XORC2) by its ability to rescue a mitotic-catastrophe mutant of the
      fission yeast Schizosaccharomyces pombe. We show that immunodepletion of XORC2
      from Xenopus egg extracts abolishes the replication of chromosomal DNA but not
      elongation synthesis on a single-stranded DNA template. Indirect
      immunofluorescence indicates that XORC2 binds to chromatin well before the
      commencement of DNA synthesis, and even under conditions that prevent the
      association of replication licensing factor(s) with the DNA. These findings
      suggest that Orc2 plays an important role at an early step of chromosomal
      replication in animal cells.

PMID- 8552194
TI  - Interaction of Cdc2 and Cdc18 with a fission yeast ORC2-like protein.
AB  - In fission yeast, Cdc2 kinase has both positive and negative roles in regulating
      DNA replication, being first necessary for the transition from G1 to S phase and
      later required to prevent the re-initiation of DNA replication during G2. We
      report here that Cdc2 interacts with Orp2, a protein similar to the Orc2
      replication factor subunit of Saccharomyces cerevisiae origin recognition complex
      (ORC). ORC binds chromosomal origins and is essential for chromosomal replication
      initiation. Fission yeast Orp2 is required for DNA replication and interacts with
      the rate-limiting replication activator Cdc18. Cells lacking Orp2 undergo
      aberrant mitosis, indicating that Orp2 is involved in generating a checkpoint
      signal. These findings suggest that ORC functions are conserved among eukaryotes
      and provide evidence that Cdc2 controls DNA replication initiation by acting
      directly at chromosomal origins.

PMID- 8552195
TI  - Calcium oscillations in mammalian eggs triggered by a soluble sperm protein.
AB  - At fertilization in mammals, the sperm induces a characteristic series of Ca2+
      oscillations in the egg which serve as the essential trigger for egg activation
      and early development of the embryo. It is not known how the sperm initiates this
      fundamental process, however, nor has any pathway linking sperm-egg membrane
      receptor binding with intracellular Ca2+ release been demonstrated.
      Microinjection of sperm extracts into mammalian eggs elicits Ca2+ oscillations
      identical to those occurring at fertilization, which suggests that sperm may
      introduce a Ca2+ oscillation-inducing factor into the egg on gamete membrane
      fusion. Here we identify a soluble sperm protein that exhibits Ca2+ oscillation
      inducing ('oscillogen') activity in eggs. Sperm oscillogen exists as an oligomer
      with a subunit of M(r) 33K and a specific intracellular localization at the
      equatorial segment of the sperm head. Cloning of the 33K oscillogen complementary
      DNA indicates similarity with a hexose phosphate isomerase found in prokaryotes.
      This sperm-derived oscillogen, termed oscillin, may represent the physiological
      trigger for development in mammals.

PMID- 8552196
TI  - Crystal structure of a G-protein beta gamma dimer at 2.1A resolution.
AB  - Many signalling cascades use seven-helical transmembrane receptors coupled to
      heterotrimeric G proteins (G alpha beta gamma) to convert extracellular signals
      into intracellular responses. Upon nucleotide exchange catalysed by activated
      receptors, heterotrimers dissociate into GTP-bound G alpha subunits and G beta
      gamma dimers, either of which can modulate many downstream effectors. Here we use
      multiwavelength anomalous diffraction data to solve the crystal structure of the
      beta gamma dimer of the G protein transducin. The beta-subunit is primarily a
      seven-bladed beta-propeller that is partially encircled by an extended gamma
      subunit. The beta-propeller, which contains seven structurally similar WD
      repeats, defines the stereochemistry of the WD repeat and the probable
      architecture of all WD-repeat-containing domains. The structure details
      interactions between G protein beta- and gamma-subunits and highlights regions
      implicated in effector modulation for the conserved family of G protein beta
      gamma dimers.

PMID- 8552197
TI  - Gene therapy for cancer (present status).
AB  - The present status of cancer gene therapy is reviewed here in short. Two of the
      main gene therapy strategies for the treatment of cancer are discussed. The first
      main strategy is direct gene therapy which involves insertion of a functioning
      tumor suppressor gene or suppression of expression of a known oncogene. The
      second main strategy is indirect gene therapy which involves the insertion of a
      gene that modifies the cell to be more immunogenic for the host. The main
      clinical gene therapy trials are reviewed in their present state, including the
      replacement of defective tumor suppressor genes, the insertion of suicide or
      sensitivity genes, the insertion of prodrug-activating genes, and the use of
      virally directed enzyme prodrug therapies. Other topics discussed are the
      protection of stem cells from toxic effects of chemotherapy and new directions
      for gene therapy of neoplastic disease.

PMID- 8552198
TI  - Galectin-3, a laminin binding protein, fails to modulate adhesion of human
      melanoma cells to laminin.
AB  - Galectin-3 is a laminin binding protein which expression is altered in a variety
      of human carcinomas including colon, breast and endometrium. In these tumors, we
      consistently observed a down regulation of galectin-3 expression related to
      increased aggressiveness. Galectin-3 belongs to a family of galactose-binding
      lectins and binds laminin through its numerous poly-N-acetyllactosamine chains.
      To date, the exact role of galectin-3 in the complex interactions between cancer
      cells and laminin has not been clearly defined. Adhesion of melanoma cells to
      laminin is a critical event during tumor invasion and metastasis. In this study,
      we explore the possibility that galectin-3 could modulate attachment of two human
      melanoma cell lines to laminin. A2058 and A375 melanoma cell expressed galectin-3
      on their surface as demonstrated by immunofluorescence, and attached to laminin
      in an in vitro assay. We demonstrate that neither recombinant galectin-3 nor an
      affinity purified antigalectin-3 antiserum altered adhesion of A2058 or A375
      melanoma cells to laminin. Our data strongly suggest that galectin-3 is not a key
      element in adhesion of the melanoma cells to laminin. These results are not
      surprising in light of the observation that galectin-3 expression is down
      regulated in cancer and that increased adhesion to laminin is a constant feature
      of invasive cancer cells.

PMID- 8552199
TI  - Immune phenotype and some enzyme patterns in phorbol ester-induced chronic
      lymphocytic leukemia cells.
AB  - Leukemic cells from 10 patients with B-chronic lymphocytic leukemia (B-CLL) were
      isolated and cultured in the presence of 12-0-tetradecanoylphorbol 13-acetate
      (TPA) at a concentration of 8 x 10(-7) mol for 72 hours. Cells were analyzed
      before cultivation and after 72 h of cultivation with and without TPA for changes
      in surface membrane (Sm) and cytoplasmic (cyt) markers expression, presence of
      receptor for mouse rosette forming cells (MRFC) and some enzyme profiles. All B
      CLL cases studied showed typical B-cell phenotype. TPA treatment induced hairy
      cell leukemia (HCL) characteristics, given by the membrane CD22 and CD25
      expression and TRAP positivity in the majority of the cases tested. Cells had
      hairy cell-like morphology with more intensive cytoplasmic immunoglobulin (CIg)
      fluorescence staining, absent receptor for MRFC and increased activity of purine
      nucleosidephosphorylase. In common these changes indicate that TPA can induce
      hairy cell characteristics on B-CLL cells in vitro suggesting the more mature
      differentiation stage of HCL compared with CLL. Furthermore, we originally
      demonstrated that the CD22, present in the cell membrane after TPA, could be
      detected in the majority of unaffected B-CLL cells in their cytoplasm. From the
      technical point of view some intracellular CD markers and Igs of B-CLL cells in
      viable cells in suspension assayed by flow cytometry are described in this study.

PMID- 8552200
TI  - Human hematopoietic cell lines: a model system for study of minimal residual
      disease detection technique in acute leukemia.
AB  - Double immunofluorescence studies using both surface and cytoplasmic antigens
      were performed on cells of some human hematopoietic lines. We tested several
      permeabilization protocols in order to optimize, improve and simplify flow
      cytometric assay to detect the combinations of two markers present in one cell
      which could be regarded as leukemia-related markers. It was found, that buffered
      formaldehyde-acetone (BFA) fixation renders the cell membrane permeable without
      destroying surface antigens so that intracellular and cell surface markers could
      be measured simultaneously by flow cytometry. Cell lines used for the experiments
      reported here included MOLT4 T cell line, mature B cell lines DAUDI and U-266,
      and early B cell line REH-6. Results from our studies demonstrated, that in the
      absence of CD3 antigen on the surface membrane of viable MOLT4 blast cells,
      double labeling of fixed, permeabilized cells revealed 97% mCD7+, cCD3+ double
      positive cells. Two color staining with anti-CD19 and anti-CD22 monoclonal
      antibodies (MoAbs) in DAUDI cells showed, that larger part of cCD22+ cells
      expressed mCD19 antigen. CD22 antigen was absent on DAUDI cell membrane. Of great
      interest was the finding, that the marker detected by anti-CD19 MoAb which was
      absent on the membrane of U-266 cells was detected in their cytoplasm. Double
      staining of these cells revealed, that the number of mCD22+, cCD19+ double
      positive cells was 80%. Cytoplasmic CD22 antigen along with surface membrane CD19
      was used to define early B cell line REH-6 as well. Our results demonstrate
      majority of double positive cells among tested population (mCD19+, cCD22+). To
      our knowledge the presence of cytoplasmic IgM detectable by flow cytometry in REH
      6 cells, which could be so regarded as a precise and adequate counterpart to pre
      B acute leukemia cell phenotype in children, is an original finding.
      Immunological typing plays an important part in the multiple marker analysis of
      hematopoietic malignancies. Through these surface and cytoplasmic marker
      combinations minor neoplastic cell populations could be detected. Human
      hematopoietic cell lines could serve as a reliable model system for monitoring
      minimal residual disease in acute leukemia patients.

PMID- 8552201
TI  - p53 expression in breast cancer related to prognostic factors.
AB  - In this article the results of molecular marker p53 examinations were presented
      in relation to the following established breast cancer prognostic factors: age,
      histologic type, histologic grade, lymph node involvement, tumor size as well as
      estrogen a progesterone receptor status. Twenty one percent of these primary
      breast cancer specimens exhibited the overexpression of p53 protein. Significant
      associations were found between p53 overexpression and younger age, high
      histologic grade and low content of estrogen and progesterone receptors.
      Identification of p53-positive breast carcinomas potentially represents a
      clinically useful indicator of breast cancer aggressiveness.

PMID- 8552202
TI  - DNA index as prognostic factor in breast cancer.
AB  - Enzymatically dissociated cells exhibited growth in most cases while mechanically
      dissociated cells did not grow in short term cultures and were not suitable for
      cytometric study. Breast cancer cells obtained by enzymatic dissociation were
      examined for DNA content and S-phase fraction. The most of the primary and
      metastatic breast cancer cells were aneuploid. The 74% rate of invasive and 62%
      of primary breast cancers had aneuploid (> G0/G1) DNA content, 22% of metastatic
      breast cancer cells and 37% of primary tumors cells were DNA diploid or near
      diploid tumor stemlines. The means of DNA diploid and near diploid tumor cells
      were higher in primary tumors. DNA index was higher in more aggressive and
      metastatic tumors. S-phase fractions were higher in cells of metastatic tumors
      than those in primary tumors. Nuclear DNA content and S-phase fraction can be
      considered a valuable prognostic indicators in breast cancer.

PMID- 8552203
TI  - Micronucleus assay in three transplantable mouse tumors.
AB  - The cytokinesis-block micronucleus (MN) assay was performed in three mouse
      tumors: two sarcomas (SaL, MCA) and Lewis lung carcinoma (LLC). To determine the
      optimal culture durations and cytochalasin B (cyt-B) concentrations to yield the
      highest proportion of binucleate cells (BC) for each tumor, the influence of the
      cyt-B concentration (1, 2 and 3 micrograms/ml) and culture duration (24-96) were
      studied. The amount of BC and the MN frequency was investigated for the different
      radiation doses (0-4 Gy). Dose response curves were constructed using the optimal
      culture duration and cyt-B concentration for each tumor. This was 24 h of
      incubation for MCA and 48 h for SaL and LLC and 2 micrograms/ml of cyt-B. The
      tumors examined differ in the mean number of spontaneously (0 Gy) occurring MN in
      binucleate cells. These were 0.008, 0.022 and 0.044 for MCA, SaL and LLC,
      respectively. The MN frequency increased with radiation dose. LLC was found to be
      the most radiosensitive, while MCA proved to be the least radiosensitive tumor.
      The average number of MN/BC at 2 Gy of irradiation (after subtraction of the
      value at 0 Gy) ranged from 0.05 to 0.36. The highest mean value -0.36 was shown
      in LLC, the middle-0.20 in SaL, and the lowest-0.05 in MCA tumor. After higher
      doses of irradiation numerous BC with two and more MN were found in LLC tumor,
      while they were not frequently observed in MCA tumor. We did not observe an
      increase in the MN frequency with culture duration or proliferation rate of the
      tumor cells. MCA has the shortest potential doubling time (Tpot) and had the
      lowest MN frequency from three examined tumors. The MN assay has promise to be a
      rapid predictive assay of radiosensitivity.

PMID- 8552204
TI  - Phorbol ester (TPA)-induced differential modulation of cell surface antigens in
      human pluripotential leukemia (K-562) cell line: effects of protein kinase
      inhibitors with broad- and PKC selective inhibitory activity.
AB  - Phorbol ester (TPA)-induced increase in cell surface expression of adhesion
      structures, i.e. intercellular adhesion molecule-1 (ICAM-1, CD54), beta 2
      integrin LFA-1 (CD11a), complement-regulatory cell membrane protein-protein
      (CD59) and leukocyte common antigen (CD45) in human erythroid/myeloid leukemia
      cell line K-562 was inhibited by staurosporine, an inhibitor with broad, non
      selective protein kinase inhibitory profile, but not by CGP 41,251, a benzoylated
      staurosporine derivative with the selective protein kinase C (PKC) inhibitory
      activity. Neither staurosporine nor CGP 41,251 modulated TPA-induced down
      regulation of transferrin receptor (CD71). These data suggest that phorbol ester
      induced cell surface antigen modulations in K-562 cells are predominantly
      mediated by PKC-independent signalling pathways.

PMID- 8552206
TI  - Assessment of antimutagenic effects of stobadine dihydrochloride on MNNG-induced
      mutations in Chinese hamster cells V79.
AB  - Mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and antimutagenic
      effect of antioxidant stobadine (STB) were investigated by so called HGPRT/V79
      system. Cells were treated by STB before, during and after MNNG-treatment. Our
      results showed that the highest antimutagenic effect of STB was observed if the
      drug was given as a pretreatment before exposure of cells to MNNG. This effect
      was not concentration-dependent within the framework of 1.5-9 mmol. All other
      combinations of MNNG- and STB-treatment led to the weaker but statistically
      significant decrease of 6-TGr mutations. Inhibition of proteosynthesis induced by
      methylxanthine pentoxifylline in the time of pre-MNNG-treatment removed
      completely antimutagenic effects of STB. In addition to mutagenicity assays,
      cytotoxicity of STB and combined effects of MNNG and STB were studied. Trypan
      blue exclusion and growth activity of influenced cells showed that the
      application of STB (1.5 mmol) before or after MNNG (0.5 microgram/ml) treatment
      had a similar toxic effect as MNNG alone. Application of STB during MNNG
      treatment or pretreatment of cells with STB followed by combined treatment of
      cells by STB+MNNG statistically significantly decreased viability of cells. There
      are probably no relationships between the antimutagenic and the toxic effects of
      combined influence of STB and MNNG on V79 cells.

PMID- 8552205
TI  - In vitro antileukemic activity and chemical transformation of the 5'-chloro-5'
      deoxy derivative of cyclocytidine.
AB  - Hydrochloride of 5'-chloro-5'-deoxy-cyclocytidine (Cl-cC) is an analogue of
      cyclocytine hydrochloride (cC), a prodrug of the compound with the strong
      antileukemic activity arabinosylcytosine (araC). This paper is devoted to the
      study of its cytotoxic activity in vitro and to the effect of acid and alkaline
      conditions and temperature on its stability. Cl-cC inhibits not only the growth
      of L1210 leukemia cells in vitro and the DNA synthesis (IC50 = 0.09 mumol/l) but,
      at the same time, it has a weak effect on RNA synthesis (IC50 > 250 mumol/l) and
      no effect on proteosynthesis. In alkaline conditions Cl-cC is transformed to 5'
      chloro-araC and 2',5'-anhydro-araC but is more stable in acid solutions.

PMID- 8552207
TI  - Increased antioxidant enzyme activities in the colorectal adenoma and carcinoma.
AB  - Most colon carcinomas are preceded by an adenomatous polyp--adenoma-carcinoma
      sequence. Active oxygen species (AOS) can play a role in the pathogenesis of this
      process. Antioxidant enzymes (AE) are the primary defense against the deleterious
      effect of AOS. Activities of AE in 56 individuals with colorectal adenoma (CA),
      29 individuals with colorectal carcinoma (CC) and in 24 control subjects were
      examined. Biopsy specimens from the non-neoplastic colonic mucosa and from the CA
      and CC were taken during colonoscopy for histological and enzymological analysis.
      Activities of following AE were estimated: CuZn-superoxide dismutase (CuZn-SOD),
      catalase (CAT) and glutathione peroxidase (GPx). It was found that individuals
      with CA and CC were characterized by: (1) increased activities of CAT and GPx in
      non-neoplastic mucosa, that persisted in some of the patients even after removal
      of tumors; (2) increased activities of CuZn-SOD, CAT and PGx in CA and CC
      tissues. It can be inferred that the accumulation of peroxides in the non
      neoplastic colonic mucosa induced higher activities of CAT and GPx. The reasons
      of high activities of all AE in the tissues of CA and CC and their relation to
      carcinogenesis are not clear and require further studies.

PMID- 8552208
TI  - Comparison between serum levels of carcinoembryonic antigen, sialic acid and
      phosphohexose isomerase in lung cancer.
AB  - The identification and application of quantifiable tumor markers as adjuncts to
      clinical care is a story of both success and failure. The present study compared
      serum levels of carcinoembryonic antigen (CEA) with total sialic acid/total
      protein (TSA/TP) ratio and phosphohexose isomerase (PHI) in 192 untreated lung
      cancer patients as well as 80 age and sex matched controls (44 non-smokers and 36
      smokers). CEA values were significantly raised (p < 0.001) in smokers as compared
      to the non-smokers; whereas, TSA/TP and PHI values were comparable between the
      two groups of the controls. All the biomarkers were significantly elevated (p <
      0.001) in untreated lung cancer patients as compared to the controls. Receiver
      operating characteristic curve analysis revealed higher sensitivities of TSA/TP
      and PHI as compared to CEA at different specificity levels between 60% and 95%.
      Mean values of CEA, TSA/TP and PHI were higher in non-responders compared to the
      responders. The results indicate that TSA/TP and PHI are superior tumor markers
      than CEA for lung cancer patients.

PMID- 8552209
TI  - Cancer, cardiovascular mortality, and diet in Italy and the Czech Republic.
AB  - A descriptive study aimed at comparing mortality and dietary patterns in Italy
      and the Czech Republic was conducted in the period 1970-1990. Mortality from all
      causes, all cancers, selected site specific cancers and cardiovascular diseases
      were found to be generally higher in the Czech Republic than in Italy. The North
      South gradients observed within Italy have diminished in the course of the last
      twenty years, mostly due to a less contained decrease of the mortality from
      cardiovascular diseases and to a marked increase in cancer mortality for Southern
      regions compared to Central and Northern regions. The mediterranean diet with
      many health promoting, possibly protective components, mostly of vegetable
      origin, is consumed in most parts of Italy, particularly in the South. In
      contrast, a Central European diet abounding in animal products and lacking in
      fresh fruit and vegetables is generally followed in the Czech Republic. These
      differences in diet may play a role in the origin of the observed differences in
      mortality patterns. Some factors other than diet, such as smoking habits, alcohol
      consumption, endogenous factors, and occupation, that are not considered here,
      are known to be involved in the causation of some types of cancer. The results of
      this study are compatible with the hypothesis of a relevant role played by
      dietary and other life-style habits in the etiopathogenesis of neoplastic and
      cardiovascular diseases.

PMID- 8552210
TI  - Smoking habit and benign breast disease.
AB  - The possible association between cigarette smoking and the risk of benign breast
      disease (BBD) was assessed in a case-control study conducted in Gdansk, Poland,
      between 1990 and 1994. The study compared 160 women with newly diagnosed BBD
      admitted to the Gdansk Cancer Outpatients Clinic and 160 controls, women from
      outpatients clinics at the Medical University of Gdansk. There was no convincing
      evidence of an association, either positive or negative, between various
      indicators of smoking habit (smoking status, number of cigarettes smoked per day,
      duration of smoking) and the risk of BBD. Slightly lower relative risks (RRs) of
      BBD in ex-smokers of 10 or more cigarettes per day (RR = 0.9; 95% confidence
      interval, CI: 0.4-2.2), and with duration of smoking > or = 20 years (RR = 0.8;
      95% CI: 0.1-3.4), were also observed in current smokers (RR = 0.8; 95% CI: 0.4
      1.5), and (RR = 0.8; 95% CI: 0.1-3.4), but these findings were not statistically
      significant.

PMID- 8552211
TI  - Carbohydrate-deficient glycoprotein syndrome--a fourth subtype.
AB  - Two infants are described, who, we suggest, represent a fourth subtype of
      carbohydrate-deficient glycoprotein (CDG) syndrome. Both patients showed
      microcephaly and severe epilepsy with absent psychomotor development and similar
      minor dysmorphic features. There were no signs of liver dysfunction. Several
      glycoproteins in blood, including transferrin, alpha 1-antitrypsin, antithrombin
      and thyroxine-binding globulin, demonstrated abnormal isoforms suggesting a
      partial deficiency of mainly one or two sialic acid residues. Both the clinical
      picture and the glycoprotein abnormalities were different from previously defined
      types of CDG syndrome.

PMID- 8552212
TI  - Variable clinical and biochemical presentation of seven Spanish cases with
      glutaryl-CoA-dehydrogenase deficiency.
AB  - In this report, we describe seven new patients with a severe deficiency of
      glutaryl-CoA dehydrogenase in cultured skin fibroblasts. Three of the patients
      studied excreted high levels of glutaric acid. The remaining four patients
      presented a lack of significant glutaric aciduria. However, glutaric acid was
      found in increased levels in CSF. In both groups of patients, the urine glutaric
      acid levels were not related to their metabolic condition at the time of
      sampling. Hypocarnitinemia was a common finding. Some patients also showed
      defects on respiratory chain complexes in muscle biopsy. Only one patient has a
      normal psychomotor development. The other six patients are severely handicapped
      despite the attempts of different therapies. In patients with progressive
      neurological deterioration with dystonia and cerebellar signs associated with
      temporal lobe atrophy and bilateral basal ganglia damage on MRI, a glutaric
      aciduria type I (GA I) should always be investigated. The presence of glutaric
      acid in body fluids, especially in CSF, as well as plasma carnitine levels,
      should be determined. These procedures can lead to the diagnosis of glutaric
      aciduria type I.

PMID- 8552213
TI  - Proton magnetic resonance spectroscopic imaging in neonatal stroke.
AB  - To study cerebral metabolism in neonates after unilateral cerebral infarcts 4
      neonates (3 full-terms, one preterm with a gestational age of 35 weeks) with
      unilateral cerebral infarcts were examined at 7 to 49 days of postnatal age,
      using proton magnetic resonance spectroscopic imaging (1H-MRSI). Three neonates
      had infarcts of the left middle cerebral artery (MCA), one had a right posterior
      cerebral artery infarct and a more localized anterior lesion. Examinations were
      repeated in the three fullterm infants aged 2-3 months. Lactate resonances, which
      are not present in normal brain after term age, were demonstrated in two patients
      tested at 7 and 10 days of age respectively, and in one of them lactate was still
      present at two months. In all four neonates a decrease of the N
      acetylaspartate/choline (NAA/Cho) ratio was seen within the area of infarction.
      Repeated MRS of two infants at three months showed an increase in NAA/Cho ratios
      in all brain areas, but values remained below normal in the infarcts. In the
      third infant a further decrease in the NAA/Cho ratio was demonstrated in the area
      of infarction at two months. The NAA/Cho ratios in the surrounding and
      contralateral brain tissue were normal in all infants. All three infants with a
      MCA infarct developed a hemiplegia. The aforementioned metabolic alterations in
      neonates with cerebral infarcts, demonstrated using 1H-MRSI, were found to be
      confined to the area of infarction and abnormalities persisted beyond the
      neonatal period.

PMID- 8552214
TI  - Botulinum toxin in the treatment of cerebral palsy.
AB  - This paper reports the results of botulinum toxin A treatment in 13 children with
      cerebral palsy. All patients except one exhibited dynamic deformities in one hand
      or foot and changes in muscle tone of corticospinal and extrapyramidal origin.
      The primary purpose of the treatment was to improve the impaired skilled
      movements which resulted from dystonic limb posture and were the most disabling
      symptoms in the group studied. The study showed that the botulinum toxin
      treatment produced a significant improvement in functional disability in terms of
      amelioration of skilled hand movements and foot posture (p < 0.01). The
      injections took effect a few days after dystonic muscle infiltration, and the
      mean duration of improvement was 3.1 months (2.0-4.0 months). Side effects were
      negligible and transient; transitory muscle weakness was the most frequent.
      Botulinum toxin A provides a safe and effective adjuvant treatment of dystonic
      skilled movements and gait disorders in children with cerebral palsy.

PMID- 8552215
TI  - Vigabatrin in childhood epilepsy: a 5-year follow-up study.
AB  - In an retrospective uncontrolled long-term study in 30 children with intractable
      epilepsy, it was found that treatment with vigabatrin resulted in a seizure
      reduction of more than 50% at 1-year follow-up in 40% of the children. The
      responders were all children with partial seizures. Side effects were mild and
      did not lead to discontinuation of the drug. Increased numbers of seizures were
      seen in three cases. A moderate weight increase was seen in 27% of the children.
      At 5-year follow-up 7 children (23%) still maintained a seizure reduction of more
      than 50%. Trials of monotherapy in three seizure-free patients were unsuccessful.
      No further side effects were observed. A study of evoked potentials in 12
      children showed no alteration in latency and amplitudes of VEP following
      treatment with vigabatrin. Our results show that in children vigabatrin seems to
      have a stable effect even though a few children may experience a breakthrough of
      seizures. The presented results together with previous reports on MRI-scans seem
      to indicate that even in children with a still maturing CNS vigabatrin is a safe
      drug.

PMID- 8552216
TI  - Clinical results of early orthopaedic management in Duchenne muscular dystrophy.
AB  - Although the primary defect of Duchenne muscular dystrophy has been found, there
      is no causal treatment to alter the natural course of this disease. Based on the
      recommendations by Glorion and Rideau with early treatment of contractures of the
      hips and the lower limbs we performed a modified release of the spina muscles,
      resection of tensor fasciae latae muscle and a lengthening of the tendo calcaneus
      in 32 patients. The mean age of DMD patients at time of operation was 6.1 years.
      The mean follow-up was 3.4 years. All children underwent mobilisation the day
      after surgery. Complete correction of all contractures was immediately achieved
      after operation and kept in all but two cases up to the follow-up examination
      after 3.4 years. No loss of ambulation was observed. Our results demonstrate that
      early selective surgery in DMD patients just at or better before the onset of
      contractures without performing an additional aponeurectomy of the iliotibial
      band and percutaneous tenotomy of the hamstrings according to the original
      Glorion-Rideau technique safely prevents severe contractures and thereby delays
      the progression of scoliosis.

PMID- 8552217
TI  - Oxyradical damage and mitochondrial enzyme activities in the mdx mouse.
AB  - A number of studies have already been undertaken to investigate involvement of
      oxyradicals in muscle diseases by means of measurements of oxyradical protective
      enzymes. We investigated o-tyrosine, which is a biomarker for OH radical damage
      in vivo, in 10 mdx and 10 control mice. We also measured mitochondrial enzymes in
      muscle homogenates of 10 mdx and 10 control mice. Mdx mice had significantly
      elevated values for o-tyrosine, succinat-phenacinmetosulfat oxidoreductase. NADH
      O2 oxidoreductase and cytochrome C oxidoreductase. Our findings confirm the
      suggestion that elevated oxyradical production occurs in muscular dystrophies
      with lack of dystrophin. Furthermore, our results demonstrate that OH radical
      damage does not impair mitochondrial enzyme activities in the mdx mouse.

PMID- 8552218
TI  - Primary hypogonadism in females with infantile onset spinocerebellar ataxia.
AB  - We recently described an infantile onset spinocerebellar ataxia (IOSCA) in 19
      Finnish patients. The classification of hereditary ataxias of unknown etiology is
      difficult because of the heterogeneity of these diseases. The clinical course of
      IOSCA is homogeneous. Ataxia, muscle hypotonia, athetosis, and loss of deep
      tendon reflexes in the legs appeared around the age of 1 year. Ophthalmoplegia
      and deafness were found by school-age, and sensory axonal neuropathy and optic
      atrophy by adolescence. An acute crisis with epilepsy was a late manifestation.
      The female patients had hypogonadism. In order to define the type of hypogonadism
      and to exclude other endocrine defects we measured serum concentrations of SHBG,
      DHEAS, prolactine, testosterone/estradiol, FSH and LH in postpubertal patients.
      ACTH, hCG and GnRH tests were performed to both pre- and postpubertal patients.
      Growth was analysed, and the brain and pituitary region were examined with
      magnetic resonance imaging (MRI). The estradiol values were low and FSH and LH
      values were high in the female patients, which indicates that the hypogonadism
      was of the hypergonadotropic type. The growth of the female patients was steady
      without a significant pubertal growth acceleration. The growth and pubertal
      development of the male patients were normal. The adrenal cortical and thyroidea
      functions were normal in all patients.

PMID- 8552219
TI  - Cured of acute lymphoblastic leukaemia but lost for words.
AB  - A thirteen-year-old boy with nominal aphasia caused by simple partial status
      epilepticus is described. The aphasia disappeared with intravenous diazepam and
      has improved on oral carbamazepine. His epilepsy is probably secondary to the
      cranial irradiation and intrathecal methotrexate that he received as treatment
      for his Acute Lymphoblastic Leukaemia at the age of nine.

PMID- 8552220
TI  - Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO
      syndrome) in two Japanese siblings.
AB  - We report on two Japanese siblings (one female and one male) with PEHO syndrome
      (progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy). They
      showed profound generalized hypotonia early in infancy and developed infantile
      spasms with hypsarrhythmia within the first year of life. Abnormal eye movement
      and visual failure with optic atrophy were also observed early in infancy.
      Psychomotor development was arrested and serial neuroradiological studies showed
      slight progressive brain atrophy, dominantly of the brainstem. This is the first
      case report of PEHO syndrome, other than those dealing with the Finnish
      population.

PMID- 8552221
TI  - Mid-portion agenesis of corpus callosum in a presumed Baller-Gerold syndrome.
AB  - We report an association of trigonocephaly and thumb hypoplasia in a 6.5-year-old
      boy, diagnosed as Baller-Gerold syndrome. In addition to craniosynostosis and
      radial limb defect, which are constant in this syndrome, our patient presents two
      unusual features: the first is an epidermal nevus and the second is an agenesis
      of the middle portion of corpus callosum. This unique type of callosal agenesis
      in the context of a polymalformative disorder supports the hypothesis that
      partial agenesis of corpus callosum may be due to an event occurring before the
      12th week gestation with continued development of the midline structures.

PMID- 8552222
TI  - Painful torticollis with tongue atrophy--a different neck-tongue syndrome.
AB  - Two children were referred with neck pain, torticollis, dysarthria, and atrophy
      of the tongue. The erythrocyte sedimentation rate was markedly elevated in both
      cases. Radiologic appearances were similar. In both cases the cervical spine was
      stable. Computerised tomography showed soft-tissue swelling surrounding the
      odontoid process and distorting the theca. Magnetic resonance imaging showed
      gadolinium enhancement of the soft tissue overlying the clivus and around the
      odontoid, impinging on the medulla and high cervical cord. Biopsy in the second
      case was not diagnostic. Steroids led to a dramatic and sustained improvement in
      symptoms and a marked decrease in soft tissue mass. The history, elevated
      inflammatory indices, radiologic appearance and response to steroids, are
      consistent with an inflammatory process.

PMID- 8552223
TI  - Diaphragmatic paresis in newborns due to phrenic nerve injury.
AB  - Phrenic nerve lesions as a result of birth trauma have been reported as a cause
      of acute respiratory distress infrequently. We report recent diagnostic and
      therapeutic experiences in four newborns with birth-traumatic phrenic nerve
      injury: one bilaterally, and three unilaterally, all right-sided. In each case,
      mechanical ventilation was required for at least 16 days. Ultrasound examination
      of the diaphragm and phrenic nerve conduction studies turned out to be the
      diagnostic methods of choice. Spontaneous recovery occurred in two children and
      two became asymptomatic after operative treatment. One improved after plication
      of diaphragm and one after autologous nerve transplantation.

PMID- 8552224
TI  - Contingent and non-contingent auditory cueing in Parkinson's disease.
AB  - Parkinson's disease (PD) patients and their normal controls performed two
      experiments involving a sequential movement task, depressing a series of buttons
      at choice points along a response board. Visual or auditory cues were presented
      prior to each move according to various contingencies. PD, a disorder
      characterised by degeneration of the basal ganglia (BG), typically manifests with
      poor execution of motor sequences. We found that external cueing facilitated
      motor sequencing in PD patients. In particular, auditory cues which occurred late
      in the movement cycle maximally facilitated switching between subcomponents of a
      sequence. Based on physiological findings reported in the primate literature
      [Brotchie et al., Brain 114, 1685-1702, 1978; Schultz and Romo, Exp. Brain Res.
      1, 363-384, 1992], it is suggested that external cues enhance performance by
      replacing defective, internally generated cues (discharges) of the BG. This has
      implications for the use of physical training strategies in the treatment of PD.

PMID- 8552225
TI  - Asymmetries in the covert orienting of visual spatial attention in schizophrenia.
AB  - The presence of attentional asymmetries in patients with schizophrenia was
      investigated with particular emphasis on the effects of stage of disease,
      medication status and clinical symptom severity. A modified version of Posner's
      covert orienting of visual attention task (COVAT) which included both spatial and
      non-spatial cues was administered to six volunteer samples of subjects which
      consisted of (i) 15 unmedicated and acutely psychotic male subjects with
      schizophrenia, (ii) 15 male subjects with schizophrenia who had been receiving
      medication for 14-21 days, (iii) 10 chronic male schizophrenic subjects who had
      been receiving medication for at least two years, (iv) 10 acutely psychotic male
      subjects with non-schizophrenic psychoses, (v) 15 subjects with unilateral brain
      frontal lobe (n = 6) or parietal lobe (n = 9) lesions, (vi) and 15 male control
      subjects. Measures of saccadic and pursuit eye movements were also obtained from
      unmedicated and recently medicated subjects with schizophrenia. COVAT attentional
      asymmetries were present in unmedicated subjects with schizophrenia for the 150
      msec stimulus onset asynchrony (SOA). These asymmetries arose because reaction
      times (RTs) to right visual field targets were significantly slower than RTs to
      left visual field targets when targets followed invalid spatial or non-spatial
      cues. These asymmetries were qualitatively similar to those found in the patients
      with unilateral parietal lobe lesions. Attentional asymmetries partially resolved
      with brief periods of medication and completely resolved with long periods of
      medication. No asymmetries were found in controls nor in unmedicated subjects
      without schizophrenia. No asymmetries of ocular motor function were found. In
      schizophrenia, attentional asymmetries may reflect a deficit in the disengagement
      of visual attention from the right visual field and appear to be a stage marker
      for the disease. However this attentional deficit is dynamic and may reflect
      disruption to the neurocognitive network controlling attention at the level of
      the anterior cingulate cortex.

PMID- 8552226
TI  - The emergence of the capacity to name left visual field stimuli in a callosotomy
      patient: implications for functional plasticity.
AB  - Callosotomized patient J.W. has a well-documented history of right hemisphere
      language abilities, including an auditory and visual lexical-semantic system with
      limited phonology and syntax. However, J.W. has not previously exhibited the
      ability to name stimuli presented to the left visual field (LVF). We report the
      emergence of this ability. Experiments were conducted in which pictures and text
      were presented to the subject's LVF using retinal stabilization techniques to
      ensure lateralization. J.W. was able to correctly name approximately one-quarter
      of these stimuli under a variety of presentation conditions. The newly developed
      ability to respond verbally to complex LVF stimuli can be the result of (1)
      enhanced inter-hemispheric transfer of information via sub-cortical pathways, (2)
      sophisticated cross cueing strategies, or (3) control of motor speech in the
      right hemisphere. Although it appears that the first two mechanisms make a
      contribution to J.W.'s LVF naming performance, accuracy for unpredictable
      stimulus sets and the error patterns require acknowledgement that control of
      motor speech is now available to the right hemisphere.

PMID- 8552227
TI  - Response selection deficits in frontal excisions.
AB  - We compared the performance of patients with frontal excisions, patients with
      temporal excisions and controls in tasks involving speeded choice responses in
      which a number of variables were manipulated including: perceptual difficulty,
      stimulus and response set-size, associative complexity, and spatial stimulus
      response compatibility. Response times were sensitive to all manipulations but
      did not show any group differences. The error rates of the three groups were
      equally affected by perceptual difficulty and response set-size but frontals were
      preferentially affected by spatial S-R compatibility, associative complexity, and
      the number of stimuli per response. The results are consistent with a basic
      deficit in response selection processes which could underly many problems
      produced by frontal lesions.

PMID- 8552228
TI  - The method of vanishing cues: an evaluation of its effectiveness in teaching
      memory-impaired individuals.
AB  - The method of vanishing cues and a standard rote learning method were used to
      teach a group of memory-impaired individuals a small computer vocabulary.
      Learning was observed using both teaching methods but no advantage was found for
      either one. A second experiment was carried out where modifications were made to
      the vanishing cues procedure in order to facilitate the use of implicit memory.
      Retention was significantly better following study with rote learning than with
      the modified vanishing cues procedure. A theoretical interpretation of these
      results and the reason for the failure to replicate previous findings is given.

PMID- 8552229
TI  - Aphasic naming: what matters?
AB  - This paper investigates the factors which affect naming performance for two
      groups of aphasic subjects. The effects of word age-of-acquisition, operativity,
      frequency, familiarity, imageability, concreteness, length and the visual
      complexity of the stimulus picture were examined. In contrast to previous
      studies, we found remarkably small effects of word frequency on naming
      performance; these studies, we argue, have failed to control sufficiently for the
      effects of variables which intercorrelate with frequency. However, many patients
      were significantly affected by age-of-acquisition even when any effects of
      frequency and familiarity had been accounted for. Operativity, imageability and
      word length were also predictive of naming performance for some of the patients
      investigated, unlike visual complexity. The applicability of conclusions drawn
      from groups of aphasics is again thrown into doubt, as these two groups showed
      different patterns of predictor variables, and the variables affecting the
      performance of individuals could be different from those affecting the group.

PMID- 8552230
TI  - Impaired use of organizational strategies in free recall following frontal lobe
      damage.
AB  - Free recall, use of organizational strategies, and interference effects were
      assessed in patients with frontal lobe lesions and control subjects. In three
      experiments, patients with frontal lobe lesions exhibited impaired free recall
      and reduced use of organizational strategies in tests of memory. Reduced use of
      strategies was observed on tests of recall of unrelated items, as measured by
      subjective organization, and on tests of recall of related items, as measured by
      both category clustering and subjective organization. Frontal patients benefited
      from strategy instruction at either study or test, suggesting that both encoding
      and retrieval processes are impaired by frontal lobe damage. These findings
      indicate that the free recall impairments exhibited by patients with frontal lobe
      lesions may be caused at least in part by deficits in the use of organizational
      strategies. In addition, when first-list learning was matched for patients and
      control subjects, patients with frontal lobe lesions exhibited relatively
      increased sensitivity to proactive interference during second-list learning.

PMID- 8552231
TI  - Decreased synaptophysin in the medial temporal lobe in schizophrenia demonstrated
      using immunoautoradiography.
AB  - Synaptic alterations have been suggested, largely on theoretical grounds, to
      occur in the brain in schizophrenia. The messenger RNA encoding synaptophysin, a
      presynaptic terminal protein, is reduced in the medial temporal lobe in the
      disease, but immunocytochemical and immunoblotting data have not produced clear
      evidence for a loss of the encoded protein. Here we have used
      immunoautoradiography with an antisynaptophysin monoclonal antibody and a 35S
      labelled secondary antibody in medial temporal lobe sections from 11
      schizophrenics and 14 matched controls. In the schizophrenic cases there was an
      overall loss of synaptophysin (P < 0.02). Analysis by subfield showed significant
      reductions in the right dentate gyrus molecular layer, subiculum and
      parahippocampal gyrus, with similar trends in most other subfields. These data
      confirm that synaptophysin expression is decreased within the medial temporal
      lobe in schizophrenia. In the respect that synaptophysin is a marker of synaptic
      density, our findings suggest that reduced synaptic density may be a feature of
      the molecular neuropathology of the disease.

PMID- 8552232
TI  - Enhancement of morphine analgesia by the GABAB agonist baclofen.
AB  - Opioid-GABAergic interactions for the treatment of post-operative pain were
      investigated in two double-blind, placebo-controlled experiments. We first
      studied the effect of pre-operatively administered baclofen, a GABAB receptor
      agonist, on the analgesia produced by intravenously administered morphine, a
      predominantly mu-opioid analgesic. In a separate trial, we studied the effect of
      baclofen on the analgesia produced by pentazocine, a predominantly kappa-opioid
      analgesic. While baclofen alone did not affect the level of post-operative pain,
      morphine analgesia was significantly enhanced by baclofen compared to placebo. In
      contrast, baclofen did not affect the level of pentazocine analgesia: however,
      females receiving pentazocine showed significantly greater analgesia than males.

PMID- 8552233
TI  - N-methyl-D-aspartate receptor-mediated calcium accumulation in neocortical
      neurons.
AB  - Calcium imaging and patch-clamp recording techniques were used to investigate the
      relationship between membrane properties and intracellular calcium changes in
      response to the excitatory amino acid neurotransmitter glutamate. Application of
      glutamate to cultured neocortical neurons produced concentration-dependent
      increases in intracellular calcium, membrane depolarization and transmembrane
      current. At a low concentration (3 microM), glutamate induced only a small
      depolarization (< 10 mV), yet produced a substantial increase in intracellular
      calcium. The calcium increase was observed in the presence of extracellular
      magnesium, was dependent on extracellular calcium, was blocked by an N-methyl-D
      aspartate receptor antagonist, and was not affected by manipulation of
      intracellular calcium stores. This low concentration of glutamate also induced
      membrane currents that exhibited an N-methyl-D-aspartate-like unconventional
      voltage dependence. When glutamate was increased to a concentration known to
      produce excitotoxicity (500 microM), large depolarizations and membrane currents
      were induced, which rapidly reversed following prolonged glutamate applications.
      Changes in intracellular calcium in response to 500 microM glutamate had both
      voltage-sensitive and -insensitive components, and consistently remained elevated
      following removal of glutamate. These results indicate that low concentrations of
      glutamate can preferentially activate N-methyl-D-aspartate receptors, leading to
      increases in intracellular calcium. Functionally this may be involved in N-methyl
      D-aspartate receptor responses to ambient extracellular glutamate. In addition, N
      methyl-D-aspartate receptor-mediated calcium influx and subsequent depolarization
      induced by high glutamate concentrations can produce alterations in intracellular
      calcium homeostasis, which may play an important role in excitotoxicity.

PMID- 8552234
TI  - Potentiation of N-methyl-D-aspartate-receptor-mediated currents detected using
      the excised patch technique in the hippocampal dentate gyrus.
AB  - The excised patch mode of the patch-clamp technique has been used to record
      isolated patch N-methyl-D-aspartate-receptor-mediated currents (patch NMDA
      receptor-currents) evoked by electrical stimulation in the dentate gyrus of the
      hippocampal slice. The patch NMDA-receptor-currents were recorded by placing a
      patch of membrane isolated from the cell body in the inner molecular layer of the
      dentate gyrus and applying stimulation to the proximal commissural/associational
      pathway. The patch NMDA-receptor-currents, recorded at +40 mV in the presence of
      AMPA-receptor and GABAA-receptor antagonists, consisted of two to six summated
      unitary openings of NMDA-receptor channels, lasting several hundred milliseconds.
      Tetanic pathway stimulation evoked a rapid increase in the amplitude of the patch
      NMDA-receptor-currents which lasted for a period of at least 20 min following the
      tetanus. The study suggests that the potentiation of the patch NMDA-receptor
      currents is due to either an increase in transmitter release, or alternatively,
      to the release of an extracellular messenger which directly enhances NMDA
      receptor responsiveness.

PMID- 8552235
TI  - The activity of hippocampal interneurons and pyramidal cells during the response
      of the hippocampus to repeated auditory stimuli.
AB  - Interneurons and pyramidal cells were identified electrophysiologically in the
      hippocampus of anesthetized rats. Paired tones were presented 500 ms apart, and
      the resulting neuronal response was compared to differences in the amplitude of
      an auditory evoked potential (N40) elicited by each of the tones. Generally, the
      N40 elicited in response to the second tone is less than the response to the
      first. Pyramidal cells exhibited their most pronounced activation within 40 ms
      after the first tone. The post-stimulus discharge activation of interneurons was
      less than the pyramidal cells, but activation of different interneurons occurred
      at various times throughout the interval between the two tones. The presence or
      absence of suppression of N40 amplitude in the paired stimulus paradigm
      correlated with differences in the auditory response of both the interneurons and
      pyramidal cells. The activity of interneurons in relationship to gating of
      hippocampal auditory response is discussed.

PMID- 8552236
TI  - Synaptic expression of the high-affinity kainate receptor subunit KA2 in
      hippocampal cultures.
AB  - Non-N-methyl-D-aspartate glutamate receptors are responsible for fast excitatory
      neurotransmission in the mammalian CNS. These receptors are rapidly activated and
      desensitized in the presence of glutamate, and are often further subdivided into
      alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid and kainate receptors
      based on their selective agonists. Non-NMDA glutamate receptors are composed of
      multiple subunits which recently have been cloned, and studies on the recombinant
      glutamate receptors have helped clarify the distinctions between AMPA and kainate
      preferring glutamate receptors. Although the subunits which make up both AMPA and
      kainate receptors have a widespread distribution, most currents recorded in vivo
      are characteristic of recombinant AMPA receptors. To help clarify the functional
      role of high-affinity kainate receptors, we have characterized the expression of
      a high-affinity kainate receptor subunit, KA2, in cultured hippocampal neurons.
      Using immunocytochemistry, we found that KA2 was expressed in hippocampal neurons
      at all times during the development of the cells in culture, and the subunit was
      enriched in dendritic spines after about 14 days. The subcellular distribution of
      KA2 paralleled that of the AMPA receptor subunit GluR1, with the AMPA and kainate
      subunits being colocalized at all times in culture. The enriched KA2
      immunoreactivity co-localized with the synaptic vesicle protein synaptophysin at
      the resolution of light microscopy, indicating synaptic localization of KA2.
      Although the kainate subunit KA2 co-localized with the AMPA subunit GluR1, co
      immunoprecipitation experiments demonstrated a direct interaction between the
      AMPA receptor subunits GluR1 and GluR2/3, but not between GluR1 and the kainate
      subunits GluR6/7 or KA2. We therefore, conclude that both AMPA and kainate
      receptor subunits are enriched in the same dendritic spines, yet do not combine
      to form receptor complexes.

PMID- 8552237
TI  - Hyperthermia depletes adenosine triphosphate and decreases glutamate uptake in
      rat hippocampal slices.
AB  - The central nervous system is especially vulnerable to hyperthermia-induced
      dysfunction, yet the mechanism for this susceptibility is poorly understood. High
      levels of adenosine triphosphate are necessary to maintain normal re-uptake of
      glutamate and aspartate, the major excitatory amino acids, by excitatory amino
      acid co-transporters. We hypothesized that excitotoxic neurotransmitters
      accumulate extracellularly when hyperthermia depletes adenosine triphosphate,
      leading to decreased uptake or release of excitatory amino acids by these co
      transporters. Incubation of hippocampal slices at 42 degrees C, a temperature
      that results in coma in vivo, reduced adenosine triphosphate to 70% of control
      values and decreased uptake of the transportable excitatory amino acid analogue,
      D,L threo-beta-hydroxyaspartate, to 50% of control values. The degree of
      adenosine triphosphate depletion induced by hyperthermia was highly correlated
      with decreases in excitatory amino acid uptake. Severe adenosine triphosphate
      depletion (< or = 20% of control) induced by hyperthermia in combination with
      metabolic insults was highly correlated with the release of endogenous glutamate
      and aspartate. Preloading slices with excitatory amino acid analogues potentiated
      hyperthermia-induced alterations of excitatory amino acid transport, strongly
      suggesting that the hyperthermia-induced changes were largely due to altered
      excitatory amino acid co-transporter activity. Immunocytochemical studies
      suggested glutamate-like immunoreactivity was lost from axonal terminals during
      hyperthermia in a similar manner to losses induced by metabolic toxins.
      Hyperthermia due to infectious diseases or heat stroke my induce disorientation
      and coma. These dysfunctions may be due, in part, to altered excitatory amino
      acid transport induced by adenosine triphosphate depletion.

PMID- 8552238
TI  - Selective laser-activated lesioning of prelabeled fetal hippocampal grafts by
      intracellular photolytic chromophore.
AB  - Selective removal of grafted tissue is critical to assess the functional role of
      that tissue in the host, yet is technically difficult for well-dispersed neural
      grafts. We labeled fetal hippocampal cells with both a nuclear marker (5'
      bromodeoxyuridine) and a cytoplasmic marker (latex microspheres) before grafting
      into normal adult hippocampus. A nontoxic chromophore, chlorin e6, was conjugated
      on to the surface of latex microspheres of the treatment group. Chlorin e6
      produces cytotoxic singlet oxygen only during photoactivation. Grafted animals
      received transcranial exposure to various intensities of near-infrared laser
      light. Following laser exposure, grafts were observed in all groups except in
      transplants prelabeled with chlorin e6 latex microspheres. An optimal laser
      exposure of 50-100 J/cm2 (4-8 min) was found to selectively remove only the
      chlorin e6-containing grafted cells. With increasing doses of laser illumination,
      non-specific lesions of the host tissue surrounding the graft were induced.
      Quantitative graft analysis, in the absence of laser exposure, indicated that the
      survival of grafted cells was similar between control transplants labeled with
      latex microspheres alone and grafts labeled with latex microspheres plus chlorin
      e6. This is further evidence that chlorin e6 by itself was not toxic without
      laser exposure. The results clearly demonstrate that singlet oxygen-induced cell
      photolysis can result in selective, non-invasive removal of dispersed grafted
      cells located in adult hippocampus. This technique may facilitate defining
      specific mechanisms of action of grafted cells which mediate functional recovery
      in different host conditions.

PMID- 8552239
TI  - Effects of lesions of prefrontal cortex, amygdala, or fornix on behavioral
      sensitization to amphetamine: comparison with N-methyl-D-aspartate antagonists.
AB  - Behavioral sensitization to amphetamine involves the mesoaccumbens dopamine
      system and is accompanied by cellular changes in this system. Excitatory amino
      acid antagonists, when co-administered with amphetamine, prevent both behavioral
      sensitization and associated changes in the mesoaccumbens dopamine system. This
      suggests that excitatory amino acid-dependent events are critical to the
      initiation of sensitization. This study sought to identify excitatory amino acid
      projections required for sensitization, focusing on projections to the nucleus
      accumbens or ventral tegmental area. The major excitatory projections to the
      nucleus accumbens originate in the prefrontal cortex, amygdala and hippocampus.
      The prefrontal cortex and amygdala also send excitatory projections to the
      ventral tegmental area. Ibotenic acid lesions of the prefrontal cortex or
      amygdala and electrolytic lesions of the fornix were performed in rats. After one
      week of recovery, rats were treated with water or 2.5 mg/kg amphetamine for six
      days and challenged with amphetamine on day 8. Activity was tested in photobeam
      cages on days 1 and 8. On day 1, control and sham-lesioned rats exhibited
      stereotyped behaviors followed by a period of post-stereotypy locomotion. On day
      8, sensitization was evident as an enhancement of both stereotypy and post
      stereotypy locomotion. Co-administration of N-methyl-D-aspartate antagonists [MK
      801 (dizocilpine maleate) or CGS 19755] with amphetamine prevented the
      development of sensitization of both stereotypy and post-stereotypy locomotion.
      Neither antagonist, however, prevented the expression of sensitization. None of
      the lesions completely mimicked these effects of N-methyl-D-aspartate
      antagonists. Lesions of hippocampal projections traveling in the fornix produced
      a general disinhibition of locomotor activity, but did not prevent sensitization
      of either stereotypy or post-stereotypy locomotion. Lesions of the prefrontal
      cortex failed to prevent sensitization of stereotypy was obtained following
      repeated amphetamine administration. However, like prefrontal cortical lesions,
      amygdala lesions prevented sensitization of post-stereotypy locomotion. When
      interpreted in the light of previous studies demonstrating the importance of the
      ventral tegmental area in the initiation of sensitization, the present results
      suggest a likely role for neuronal circuits involving the prefrontal cortex,
      amygdala and ventral tegmental area in the development of sensitization of post
      stereotypy locomotion following repeated amphetamine administration. Such
      circuits may initiate sensitization through a mechanism involving excitatory
      amino acid regulation of the activity of mesoaccumbens dopamine neurons. Parallel
      circuits, involving other brain regions, may similarly contribute to
      sensitization of stereotyped behaviors.

PMID- 8552240
TI  - Repeated amphetamine administration induces a prolonged augmentation of
      phosphorylated cyclase response element-binding protein and Fos-related antigen
      immunoreactivity in rat striatum.
AB  - Semi-quantitative immunocytochemistry was used to investigate the levels of
      cyclase response element-binding protein, phosphorylated cyclase response element
      binding protein, Fos and Fos-related antigen immunoreactivity in the striatum of
      rats after acute or repeated amphetamine administration. Rats were perfused 20
      min (phosphorylated cyclase response element-binding protein) or 2 h (cyclase
      response element-binding protein, phosphorylated cyclase response element-binding
      protein, Fos, Fos-related antigen) after a single injection (5 mg/kg, i.p.) or
      five daily injections of amphetamine. The latency to onset of stereotypical
      behaviors was significantly reduced in rats exposed to repeated amphetamine as
      compared to acute amphetamine, indicating development of behavioral
      sensitization. Cyclase response element-binding protein immunoreactivity was not
      altered in the dorsal or ventral striatum following acute or repeated
      amphetamine. Phosphorylated cyclase response element-binding protein
      immunoreactivity was significantly induced 20 min, but not 2 h, following acute
      amphetamine, whereas a significant induction of phosphorylated cyclase response
      element-binding protein immunoreactivity was found 20 min and 2 h after repeated
      amphetamine in the dorsal striatum only. Fos immunoreactivity was significantly
      induced in the dorsal striatum following acute and repeated amphetamine. Fos
      immunoreactivity in the core of the nucleus accumbens was significantly increased
      following repeated amphetamine only. Acute amphetamine induced, and repeated
      amphetamine further augmented, Fos-related antigen immunoreactivity in the dorsal
      striatum, while not affecting Fos-related antigen immunoreactivity in the nucleus
      accumbens. These data demonstrate that repeated amphetamine administration
      results in a prolonged induction of phosphorylated cyclase response element
      binding protein and Fos-related antigen immunoreactivity in the dorsal striatum,
      indicating that alterations in striatal gene expression associated with the
      development of behavioral sensitization may be mediated, in part, by these
      transcription factors.

PMID- 8552241
TI  - Hypotensive stress retards associative learning in rabbits.
AB  - This study examined the effects of hypotensive stress on classical conditioning
      of the rabbit's nictitating membrane response. Hypotension, consisting of an
      approximately 45% decrease in blood pressure, was maintained for 30 min by the
      i.v. infusion of sodium nitroprusside. Twenty minutes later animals were exposed
      to a conditioning session consisting of 60 pairings of a 200 ms tone conditioned
      stimulus with a 100 ms airpuff unconditioned stimulus directed at the cornea.
      This procedure was repeated for four consecutive days. Animals exposed to the
      hypotensive stress demonstrated a significantly retarded acquisition of
      conditioned responses as measured by their frequency and onset latency as well as
      by an increase in the number of trials required to reach acquisition criteria of
      five and 10 consecutive conditioned responses as compared with controls. A
      separate group of animals received a nitroprusside infusion one day after the
      acquisition of conditioned responses to the tone conditioned stimulus. These
      animals demonstrated a normal retention of conditioned responses and a normal
      response to varying intensities of the conditioned stimulus. Hypotensive stress
      also had no effect on the frequency and topography of the unconditioned response.
      It was concluded that a decrease in blood pressure can serve as a physiological
      stressor. One of the reactions to this stress consists of a retardation in the
      formation of associations during a learning task, without any decrease in the
      ability to retrieve previously learned material.

PMID- 8552242
TI  - Electrophysiological differences between Purkinje cells in organotypic and
      granuloprival cerebellar cultures.
AB  - Organotypic cerebellar cultures derived from newborn mice were exposed to
      cytosine arabinoside for the first five days in vitro to destroy granule cells
      and functionally compromise glia. Such granuloprival cultures undergo a circuit
      reorganization featured by Purkinje cells sprouting recurrent axon collaterals
      that hyperinnervate other Purkinje cells. Intracellular recordings were used to
      compare the electrophysiological properties of Purkinje cells in granuloprival
      cultures to those of Purkinje cells in standard cultures. Purkinje cells in
      granuloprival cultures have similar membrane potentials to those of Purkinje
      cells in standard cultures, but have a lower input resistance. A reduced input
      resistance could affect the effectiveness of inhibitory synaptic input.
      Intracellular recordings from Purkinje cells of standard cerebellar cultures
      between 13 and 21 days in vitro exhibit spike activity consisting of a mixture of
      complex and simple spikes. The complex spikes contain a fast rising action
      potential followed by a depolarizing potential on which a plateau and several
      spike-like components are superimposed. This type of activity has been observed
      in mature Purkinje cells in vivo and in vitro. By contrast, at resting membrane
      potential Purkinje cells in granuloprival cultures have simple spike activity
      reminiscent of the type of activity seen in immature Purkinje cells, while at
      hyperpolarized potentials they generate complex spikes. These observations
      indicate differences in the expression of intrinsic electrophysiological
      properties underlying complex spike generation between Purkinje cells of
      organotypic and granuloprival cerebellar cultures. Our results illustrate the
      considerable plasticity of Purkinje cells in the presence of altered neuronal
      circuitry. In the absence of normal excitatory input, their spontaneous activity
      is regulated by intrinsic membrane properties.

PMID- 8552243
TI  - Excitatory amino acid-induced currents in rat septal cholinergic neurons in
      culture.
AB  - Whole-cell voltage-clamp recordings were used to study excitatory amino acid
      induced currents in neurons isolated from the septum of fetal rat brains. The
      neurons were cultured for more than four weeks on a feeder layer composed of
      glial cells obtained from the septal region. Septal neurons were either fusiform,
      triangular or multipolar and 83% of cells showed acetylcholinesterase activity. L
      Glutamate, kainate, quisqualate and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA) applied by local perfusion produced inward currents
      (Iglu, Ikai, Iquis and IAMPA, respectively) at -44mV which increased in amplitude
      with increasing concentration of agonist; they desensitized when induced at
      higher concentrations except for the Ikai. The EC50s for the peak Ikai and
      sustained Iglu, Iquis and IAMPA were 55, 13, 0.39 and 3.5 microM, respectively. 6
      Cyano-7-nitroquinoxaline-2,3-dione (CNQX) depressed Ikai and IAMPA evoked at a
      concentration of 10 microM (IC50s: 0.58 and 0.84 microM, respectively). Schild
      analysis for the CNQX action on Ikai gave a dissociation constant of 0.27 microM
      for CNQX. n-Methyl-D-aspartate (NMDA) (with glycine, 3 microM) produced an inward
      current (INMDA) at -44 mV whose peak amplitude enhanced with increased
      concentrations (EC50 = 32 microM). INMDA was potentiated by glycine (EC50 = 0.15
      microM) and inhibited by D-2-amino-5-phosphovalerate (IC50 = 9.9 microM for INMDA
      evoked at a concentration of 50 microM). MK-801 (0.1-10 microM) inhibited INMDA
      in a dose- and use-dependent manner. INMDA was (0.1-10 microM) inhibited INMDA in
      a dose- and use-dependent manner. INMDA was potentiated by spermine (EC50 = 247
      microM; 91% increase at 1mM) in a manner independent of holding potential (VH).
      INMDA was inhibited by Mg2+ and Zn2+ (IC50 = 673 and 39 microM, respectively, at 
      44 mV) in a manner dependent on VH; the magnitudes of a depolarization required
      for an e-fold increase in their IC50s in a range of -64 to -24 mV were 16 and 22
      mV, respectively. The action of Zn2+ was independent of VH > -24 mV. Current
      voltage relations for Ikai, Iquis and IAMPA exhibited outward rectification,
      while that of INMDA showed a region of negative conductance at VH < -30 mV, which
      disappeared in a Mg(2+)-free solution. Reversal potentials for Ikai, Iquis, IAMPA
      and INMDA were close to 0 mV, indicating the involvement of non-specific cation
      channels. Increasing extracellular Ca2+ concentration from 2.4 to 30 mM did not
      affect the Ikai and Iquis, reversal potential showing negligible Ca2+ component,
      but shifted INMDA reversal potential to a more positive potential, yielding a
      ratio of Ca2+ permeability to that of monovalent cation to be 13. Cholinergic
      septal neurons in culture express non-NMDA-(AMPA/kainate-) and NMDA-type of
      glutamate receptor channels. Their properties were quantitatively similar to
      those of glutamate receptor channels on other types of neurons in the brain
      except for the actions of endogenous neuromodulators (Mg2+, Zn2+ and spermine) on
      NMDA receptor channels. It is suggested that NMDA receptor channels on different
      types of neurons may play a distinct role depending on a difference in the
      actions of these neuromodulators.

PMID- 8552244
TI  - Cholinergic nucleus basalis neurons are excited by histamine in vitro.
AB  - Considerable evidence has shown that both cholinergic and histaminergic neurons
      in the brain may act to facilitate processes of cortical activation that occur
      during wakefulness. In the present study, the potential influence of
      histaminergic neurons upon cholinergic neurons of the basal forebrain was
      investigated in guinea-pig basal forebrain slices. We found that
      electrophysiologically identified and immunohistochemically verified cholinergic
      neurons of the nucleus basalis were depolarized and excited by histamine, as
      manifested by an increase in tonic firing. The depolarization was associated with
      an increase in membrane input resistance. The effect of histamine persisted in
      the presence of either tetrodotoxin or a high-magnesium/low-calcium solution,
      indicating that it is postsynaptic. By a process of elimination, the
      participation in this response of the three described histamine receptors was
      examined. Involvement of H3 receptors was excluded on the basis that the H3
      agonist (R)-alpha-methyl-histamine had no direct effect, and the H3 antagonist,
      thioperamide, did not block the effect of histamine. In contrast, the presence of
      a small response to impromidine, a selective agonist of H2 receptors, and the
      partial block of the response to histamine by the H2 receptor antagonist,
      cimetidine, indicated the participation of H2 receptors. Finally, the complete
      elimination of histamine's effect occurred when low doses of the H1 antagonist,
      mepyramine, were added to the H2 antagonist, cimetidine, indicating the
      involvement and predominance of H1 receptors in the response. Our data thus
      suggest that histamine excites nucleus basalis cholinergic neurons by a
      concomitant activation of H1 and H2 receptors. Histaminergic tuberomammillary
      neurons may accordingly facilitate tonic firing of cholinergic neurons during
      wakefulness. Cholinergic basalis neurons could thus act in tandem with
      histaminergic neurons during periods of arousal to collectively promote
      widespread cortical activation.

PMID- 8552245
TI  - Putative cholinergic neurons of the pedunculopontine tegmental nucleus projecting
      to the superior colliculus consist of sensory responsive and unresponsive
      populations which are functionally distinct from other mesopontine neurons.
AB  - We examined the sensory properties of putative cholinergic neurons of the
      pedunculopontine tegmental nucleus projecting to the superior colliculus.
      Projection neurons were identified by antidromic activation from the
      contralateral posterior superior colliculus; stimulation of the anterior half was
      essentially ineffective. Identified neurons fell into two groups, one with a
      somatosensory input (39%) and one without a sensory input. Somatosensory
      responsive projection neurons were low threshold and rapidly adapting. Receptive
      fields were contralateral (94%) and predominantly orofacial (57%). Sensory
      responsive and unresponsive projection neurons were intermingled within the
      pedunculopontine tegmental nucleus as identified histologically by reduced
      nicotinamide adenine dinucleotide phosphate diaphorase or acetylcholinesterase.
      The properties of neurons outside the nucleus differed significantly. They could
      not be activated antidromically from the superior colliculus; many had ipsi- or
      bilateral receptive fields (75%) and wide dynamic range or nociceptive response
      patterns (52%). The presence of two functionally distinct groups of projection
      neurons implies a dual or more complex modulation of tectal neurons by the
      pedunculopontine tegmental nucleus. The pedunculopontine tegmental nucleus has
      been implicated in a multiplicity of behaviors and, in particular, in rapid eye
      movement sleep and alerting or arousal functions. By virtue of its many
      connections with the basal ganglia, limbic system and reticular structures, the
      projection to the superior colliculus of two distinct groups may provide an
      important differentiating element of the tectal organization of orienting and
      spatial cognitive behavior.

PMID- 8552246
TI  - Sexual dimorphism and sex steroid modulation of glial fibrillary acidic protein
      messenger RNA and immunoreactivity levels in the rat hypothalamus.
AB  - By using the techniques of in situ hybridization histochemistry and
      immunocytochemistry, we have found that both glial fibrillary acidic protein
      messenger RNA levels and glial fibrillary acidic protein immunoreactive surface
      density in the arcuate nucleus and median eminence are modulated by both the
      neonatal and adult sex steroid environments. No effect was seen on the number of
      immunoreactive glia. Intact adult males had significantly higher glial fibrillary
      acidic protein messenger RNA levels and glial fibrillary acidic protein
      immunoreactive surface density than females. Both adult and neonatal castration
      of male animals significantly reduced glial fibrillary acidic protein messenger
      RNA levels and glial fibrillary acidic protein immunoreactive surface density.
      Neonatal and adult testosterone treatment increased both of these parameters in
      both sexes; however, there was no additive effect of the steroid treatments.
      Glial cells are involved in the proliferation, survival, migration and maturation
      of neurons, as well as in the modulation of synaptic connectivity, and therefore
      it follows that hormonal modulation of glia may mediate some of the known steroid
      effects on neurons. The data reported here show that astroglia are significantly
      influenced by both the neonatal and adult sex steroid environments and suggest
      that some of the steroid effects on neurons during both of these developmental
      periods may be mediated, at least in part, through modulation of glial cells.

PMID- 8552247
TI  - Neurotensin in the lateral hypothalamic area: origin and function.
AB  - The origin of neurotensin in the lateral hypothalamus was investigated by means
      of fluorescent retrograde tract tracing and neurotensin-like immunoreactivity.
      Following fluorescent retrograde tract tracing with FluoroGold combined with
      neurotensin immunohistochemistry in the rat brain, numerous neurotensin
      immunoreactive neurons with projections to the posterior lateral hypothalamic
      area were identified in the central nucleus of the amygdala, perifornical area
      and the parabrachial nucleus. Fewer numbers of neurotensin-positive neurons with
      projections to the lateral hypothalamic area were observed in the bed nucleus of
      the stria terminalis, lateral septal nucleus, medial preoptic area, peri- and
      paraventricular nuclei of the hypothalamus, anterior lateral hypothalamic area
      and dorsal raphe nucleus. In addition, the role of neurotensin in the modulation
      of autonomic regulatory input from the insula was investigated. The lateral
      hypothalamic area was surveyed for single units responding to electrical
      stimulation (500-900 microA, 0.5 Hz) of sites in the insular cortex from which
      cardiovascular pressor or depressor responses could be elicited. These units were
      tested for the influence of neurotensin on responses to stimulation of the
      insular cortex. Of 60 spontaneously firing neurons, 27 units responded to
      electrical stimulation of cardiovascular sites in the insula. Of the units
      responding to stimulation of cardiovascular sites in the insula, 14 units showed
      excitation only, 10 units showed excitation followed by inhibition and three
      units showed inhibition. Iontophoresis of 0.1-1.0 mM neurotensin (25-100 nA, pH
      5.0-6.0) potentiated six of the excitatory responses and showed no effect on the
      inhibitory responses. In addition, nine neurons showed an increase in spontaneous
      activity with iontophoresis of neurotensin. Of these neurons, three were excited
      by insular stimulation and six did not respond. These findings indicate the
      likely origin of neurotensin in the lateral hypothalamic area and demonstrate
      that neurotensin has a role in the modulation of some of the cardiovascular
      regulatory input from the insular cortex.

PMID- 8552248
TI  - Distribution of NADPH-diaphorase staining and light-induced Fos expression in the
      rat suprachiasmatic nucleus region supports a role for nitric oxide in the
      circadian system.
AB  - Nitric oxide serves as a messenger molecule in some neuronal systems that use
      glutamate as a transmitter and it has been shown that glutamate mediates the
      transmission of photic signals by retinal ganglion cell axons terminating in the
      hypothalamic suprachiasmatic nucleus, site of the circadian pacemaker in rodents.
      Recent experiments have demonstrated that pharmacological treatments which block
      nitric oxide synthesis by nitric oxide synthase prevent glutamate-induced phase
      shifts of the cell firing rhythm in suprachiasmatic nucleus slice preparation in
      vitro; similar treatments were found to inhibit light transmission to the
      suprachiasmatic nucleus as well as light-induced phase shifts in activity rhythms
      in vivo, implicating nitric oxide in circadian light signalling in vivo. There is
      limited information, however, about the presence and function of nitric oxide
      synthase-containing neurons within retinorecipient regions of the rodent
      suprachiasmatic nucleus. In the present study we used NADPH-diaphorase
      histochemistry and immunostaining for the nuclear phosphoprotein Fos to assess
      the co-distribution of nitric oxide synthase-containing neurons and light
      responsive cells in the rat suprachiasmatic nucleus region. A strong convergence
      between NADPH-diaphorase-stained cell bodies and fibres and cells that expressed
      Fos in response to photic stimulation was noted in the anterior periventricular
      nucleus, suprachiasmatic preoptic nucleus, retrochiasmatic area, the inter
      suprachiasmatic nucleus region, and the dorsal aspect of the optic chiasm, below
      the suprachiasmatic nucleus. A similar convergence between NADPH-diaphorase
      stained fibres and Fos-immunoreactive cells was noted inside the suprachiasmatic
      nucleus, but the number of NADPH-diaphorase-stained elements found in this region
      was substantially low compared with that found in retinorecipient regions
      bordering the nucleus. In many cases both inside and outside the suprachiasmatic
      nucleus, the Fos-immunoreactive cells appeared to make direct contact with NADPH
      diaphorase-stained cells or fibres, but no co-localization of Fos
      immunoreactivity and NADPH-diaphorase histochemical activity within individual
      cells was detected. Extensive co-distribution of NADPH-diaphorase-stained cells
      and fibres and cells that express Fos in response to photic stimulation in the
      suprachiasmatic nucleus region is in line with the hypothesis that nitric oxide
      participates in the mechanism mediating circadian light signalling in the
      suprachiasmatic nucleus. However, lack of co-localization of the two markers to
      individual cells rules out the possibility that retinorecipient cells in the
      suprachiasmatic region synthesize and release nitric oxide when photically
      activated. Instead, the results support the possibility that photic stimulation
      triggers nitric oxide synthesis in nitric oxide synthase-containing neurons
      located near the photically-activated cells.

PMID- 8552249
TI  - The reaction of Helix photosensitive neurons to light and cyclic GMP.
AB  - The effect of light and cyclic nucleotides (cGMP and cAMP) on a group of
      identified photosensitive neurons in Helix pomatia left parietal ganglion was
      examined. The onset of light induces in these cells a slow inward current shift
      associated with decrement of slope conductance. The reversal potential (Erev) of
      the light induced current (IL) and its changes due to altered extracellular
      concentration of potassium support the assumption that (IL) is due to suppression
      of K+ conductance. Elevation of intracellular concentration of cyclic GMP by
      adding 8-bromo-cGMP into the bathing solution or by injecting the nucleotide into
      the cell mimics, in all cases, the effect of light: it produces an inward current
      accompanied by decrement of slope conductance. The effect of elevation of cAMP
      was inconsistent. The I-V relations of IL and IcGMP follow a similar course and
      have a common Erev. The assumption that 3',5'-cyclic GMP is increased by light is
      also supported by comparing the effect of light and the cyclic nucleotide on the
      action potential. Both light and 8-bromo-cGMP broaden the action potential by
      increasing the voltage-dependent Ca2+ current.

PMID- 8552250
TI  - Intra-amygdaloid projections of the basolateral and basomedial nuclei in the cat:
      Phaseolus vulgaris-leucoagglutinin anterograde tracing at the light and electron
      microscopic level.
AB  - The amygdaloid complex plays an essential role in auditory fear conditioning of
      the Pavlovian type. The available evidence suggests that the lateral nucleus is
      the input station of the amygdala for auditory conditioned stimuli, whereas the
      central medial nucleus is the output for conditioned fear responses. However, the
      intrinsic pathway transmitting auditory information about the conditioned
      stimulus from the lateral to the central medial nuclei is unknown as there are no
      direct projections between these nuclei. The present study was undertaken to
      determine if the main intra-amygdaloid targets of the lateral nucleus, namely the
      basomedial and basolateral nuclei, project to the central medial nucleus. To this
      end, iontophoretic injections of the anterograde tracer Phaseolus vulgaris
      leucoagglutinin were performed in these nuclei. To rule out the possibility that
      the anterograde labeling reflected passing fibers merging with the major fiber
      bundles that course in and around the central medial nucleus, labeled terminals
      and varicosities were observed in the electron microscope. It was determined that
      the basolateral and basomedial nuclei have partially overlapping intraamygdaloid
      targets. They both project to the central medial nucleus, nucleus of the lateral
      olfactory tract and peri-amygdaloid cortex, but have limited projections to each
      other. Small Phaseolus vulgaris-leucoagglutinin injections in both nuclei gave
      rise to prominent intranuclear projections but only the basomedial nucleus was
      found to project to the lateral and anterior cortical nuclei. At the electron
      microscopic level, all labeled axon terminals and varicosities formed asymmetric
      synapses (n = 245) with dendritic spines (83%) or with dendritic shafts (17%).
      This is the first unambiguous demonstration that the basolateral and basomedial
      nuclei project to the central medial nucleus. Since these nuclei constitute the
      main intra-amygdaloid targets of the lateral nucleus, they represent likely
      candidates for the transmission of auditory conditioned stimuli to the central
      medial nucleus in auditory fear conditioning.

PMID- 8552251
TI  - The importance of calmodulin in the accessory olfactory bulb in the formation of
      an olfactory memory in mice.
AB  - Female mice form an olfactory memory to the pheromones of the mating male, during
      a critical period after mating. Failure to form this memory results in the male
      being treated as strange, and hence, his pheromones block pregnancy. Previous
      studies have shown that formation of this memory is dependent on synaptic
      mechanisms in the accessory olfactory bulb. A number of studies have pointed to
      calmodulin as a critical mediator of synaptic plasticity. In this study we have
      examined the effects of local infusions of drugs which block calmodulin-regulated
      processes, into the accessory olfactory bulb on the formation of this memory.
      Infusions of the calmodulin antagonist calmidazolium during the critical period
      prevented memory formation. However, the specific inhibitor of calcium/calmodulin
      dependent protein kinase II, KN-62, or the selective inhibitor of
      calcium/calmodulin-dependent protein phosphatase 2B (calcineurin), FK506, was
      without effect on memory formation at any of the doses used. Instead of
      preventing memory formation, FK506 permitted the formation of a non-selective
      memory to strange male pheromones in the presence of mating, although FK506 alone
      could not induce a memory without the occurrence of mating. These results suggest
      that calmodulin in the accessory olfactory bulb is important in the formation of
      the olfactory memory to male pheromones. However, memory formation may be
      independent of calmodulin-kinase II. Calcineurin may play a role in processes
      antagonizing memory formation.

PMID- 8552252
TI  - Prevention of ischemia/reperfusion-induced alterations in synaptosomal membrane
      associated proteins and lipids by N-tert-butyl-alpha-phenylnitrone and
      difluoromethylornithine.
AB  - Previous studies in our laboratory demonstrated the alteration in the physical
      state of synaptosomal membrane lipids and proteins in ischemia/reperfusion injury
      using selective spin labels and electron paramagnetic resonance spectroscopy
      [Hall et al. (1995) Neuroscience 61, 84-89]. Since many investigations have
      provided evidence for free radical generation during ischemia/reperfusion injury,
      we investigated whether a free radical scavenger would prevent the membrane
      damage, in gerbils. Further, experiments to determine if a secondary effect of
      polyamine generation at 14 h reperfusion could be blocked by this free radical
      scavenger or by an inhibitor of ornithine decarboxylase were also carried out.
      The alterations in synaptosomal membrane integrity observed during
      ischemia/reperfusion injury were selectively neutralized by treatment with the
      free radical spin trap N-tert-butyl-alpha-phenylnitrone or an inhibitor of
      ornithine decarboxylase, difluoromethylornithine. Administration of N-tert-butyl
      alpha-phenylnitrone prior to ischemia totally abrogated both lipid and protein
      alterations observed at 1 and 14 h reperfusion. Pretreatment with
      difluoromethylornithine neutralized only the 14 h change in lipid label motion.
      Treatment with N-tert-butyl-alpha-phenylnitrone at 6 h post ischemia showed only
      a slight attenuation of the 14 h lipid effect and no change in the protein
      effect. Difluoromethylornithine treatment at 6 h post ischemia negated the 14 h
      ischemia/reperfusion injury-induced lipid effect and had no effect on the protein
      change. These data support previous suggestions that free radicals and polyamines
      play a critical role in neuronal damage and cell loss following
      ischemia/reperfusion injury and that the polyamine effect is dependent upon free
      radical generation during ischemia/reperfusion injury.

PMID- 8552253
TI  - Barosensitive neurons in the rostral ventrolateral medulla of the rat in vivo:
      morphological properties and relationship to C1 adrenergic neurons.
AB  - The aim of this study, conducted in anaesthetized rats, was to examine the
      morphology of barosensitive neurons in the rostral ventrolateral medulla and
      their immunoreactivity for a catecholamine synthesizing enzyme, tyrosine
      hydroxylase. Thirty neurons displaying inhibitory postsynaptic potentials
      following stimulation of the aortic depressor nerve were intracellularly labelled
      with Lucifer Yellow or Neurobiotin. Some of these neurons could be excited
      antidromically from the second thoracic segment of the spinal cord, with
      conduction velocities of spinal axons ranging from 1.9 to 7.2 m/s. The filled
      somas were found immediately caudal to the facial nucleus and ventral or
      ventromedial to compact formation of the nucleus ambiguus. Some dendrites reached
      the ventral medullary surface. Axons usually projected dorsomedially and then
      made a sharp rostral and/or caudal turn. The caudally projecting axon could, in
      some cases, be followed to the first cervical segment of the spinal cord. Seven
      cells issued fine axon collaterals on the ipsilateral side. These were identified
      mainly in two areas: in the rostral ventrolateral medulla (or immediately
      dorsomedial to that region), and within the dorsal vagal complex. Seven of 27
      examined cells (26%) were tyrosine hydroxylase-immunoreactive and were classified
      as C1 adrenergic neurons. No clear relationship was found between the presence or
      absence of adrenergic phenotype and the morphology of filled cells. However, the
      amplitude of aortic nerve-evoked inhibitory postsynaptic potentials was
      significantly larger in tyrosine hydroxylase-positive neurons. Possible reasons
      for the low percentage of barosensitive cells with tyrosine hydroxylase
      immunoreactivity found in this study, in comparison with previously published
      estimates, are discussed. This is the first study describing the morphology of
      neurons in this part of the medulla identified as barosensitive in vivo, and
      directly demonstrating adrenergic phenotype in a subset of these neurons.

PMID- 8552254
TI  - Directional regrowth of lesioned corticospinal tract axons in adult rat spinal
      cord.
AB  - During central nervous system development, gradients of diffusible molecules play
      an important role in the attraction of outgrowing axons. A diffusible tropic
      factor released by the cervical spinal gray matter attracts outgrowing
      corticospinal tract axons, as shown by in vitro collagen co-culture studies
      [Joosten E. A. J. et al. (1994) Neuroscience 59, 33-41]. Here we study the
      effects of local application of timed cervical spinal gray matter extracts on
      regrowth of injured corticospinal tract axons in the adult rat spinal cord. For
      local application of target-derived extracts at the site of lesion we used rat
      tail collagen type 1 as a matrix. Ingrowth of anterogradely labelled
      corticospinal tract axons into the collagen was studied four weeks after the
      spinal cord injury. No ingrowth of labelled corticospinal tract axons can be
      observed in the control experiment when collagen only was applied into the lesion
      gap. Furthermore, we found that local application of an extract derived from four
      day, but not from one-day or 16-day-old, cervical spinal cord gray matter directs
      a substantial amount of the lesioned adult corticospinal tract axons into the
      collagen implant. We conclude that directional regrowth of injured corticospinal
      tract axons in the adult rat spinal cord is possible by local application of
      timed target-derived extracts. In this respect spatiotemporal aspects are of the
      utmost importance.

PMID- 8552255
TI  - Diversity of voltage-gated calcium currents in large diameter embryonic mouse
      sensory neurons.
AB  - Voltage-gated Ca2+ currents were investigated in a subpopulation of dorsal root
      ganglion neurons (large diameter, neurofilament-positive) acutely isolated from
      13-day-old mouse embryos and recorded using the whole-cell patch-clamp technique.
      Low- and high-voltage-activated calcium currents were recorded. These currents
      could be identified and separated by their distinct (i) threshold of activation,
      (ii) ability to run-up during the early phase of recording and (iii) decay
      kinetics using Ba2+ instead of Ca2+ as the charge carrier. Among high-voltage
      activated currents, L-, N- and P-type Ca2+ currents were identified by their
      sensitivity to, respectively, the dihydropyridine agonist Bay K 8644 (5 microM)
      and antagonist nitrendipine (3 microM), omega-conotoxin GVIA (3 microM) and omega
      agatoxin IVA (30 nM). In the combined presence of nitrendipine (3 microM), omega
      conotoxin GVIA (3 microM) and omega-agatoxin IVA (30 nM), two additional high
      voltage-activated components were detected. One, blocked by 500 nM omega
      conotoxin MVIIC and 1 microM omega-agatoxin IVA, had properties similar to those
      of the Q-type Ca2+ current first reported in cerebellar granule cells. The other,
      defined by its resistance to saturating concentrations of all the blockers
      mentioned above applied in combination, resembles the R-type Ca2+ current also
      described in cerebellar granule cells. In conclusion, embryonic sensory neurons
      appear to express a large repertoire of voltage-activated Ca2+ currents with
      distinct pharmacological properties. This diversity suggests a great variety of
      pathways for Ca2+ signaling which may support different functions during
      development.

PMID- 8552256
TI  - Neuronal tachykinin NK2 receptors mediate release of non-adrenergic non
      cholinergic inhibitory transmitters in the circular muscle of guinea-pig colon.
AB  - The aims of this study were: (i) verify the usefulness of the recently described
      non-peptide antagonist, SR 142801, for blocking tachykinin NK3 receptors in the
      circular muscle of the guinea-pig colon and (ii) after occlusion of NK3 receptors
      by SR 142801, test the hypothesis that tachykinins may activate non-adrenergic
      non-cholinergic inhibitory neurons via non-NK3 receptors. In sucrose gap, we
      found that SR 142801 (0.1 microM) time-dependently inhibited the senktide-induced
      atropine (1 microM)-sensitive depolarization, action potentials and contractions
      of circular muscle of guinea-pig colon without affecting the cholinergic
      excitatory junction potential and contraction produced by single pulse electrical
      field stimulation. Likewise, SR 142801 (0.1 microM) time-dependently inhibited
      the senktide-induced non-adrenergic non-cholinergic hyperpolarization and
      relaxation of the circular muscle, without affecting the non-adrenergic non
      cholinergic inhibitory junction potentials and relaxation produced by single
      pulse electrical field stimulation. Therefore, SR 142801 is a suitable tool to
      occlude neuronal NK3 receptors in guinea-pig colon. In the presence of SR 142801
      (0.1 microM), atropine (1 microM), guanethidine (3 microM), indomethacin (3
      microM) and nifedipine (1 microM) superfusion with neurokinin A (0.3 microM)
      produced depolarization on which a series of inhibitory junction potentials were
      superimposed. The incidence, number and amplitude of the inhibitory junction
      potentials evoked by neurokinin A was partly reduced by pretreatment with either
      apamin (0.1 microM) or L-nitroarginine (30 microM) and was totally blocked by
      pretreatment with apamin plus L-nitroarginine or by tetrodotoxin (1 microM). None
      of these treatments affected the depolarization and contraction produced by
      neurokinin A. The NK1 receptor selective antagonist, GR 82,334 (3 microM), did
      not affect the responses to neurokinin A, which were abolished by the NK2
      receptor-selective antagonist GR 94,800 (0.1 microM). Substance P (0.3 microM)
      produced a large depolarization of the membrane but was poorly effective in
      producing superimposed inhibitory junction potentials. The NK1 receptor-selective
      agonist [Sar9]substance P sulfone (0.3 microM) produced large depolarization
      without inducing superimposed inhibitory junction potentials, while the NK2
      receptor-selective synthetic agonist [beta-Ala8]neurokinin A(4-10) (0.3 microM)
      produced depolarization and superimposed inhibitory junction potentials. We
      conclude that neurokinin A, in addition to direct excitation and contraction of
      circular muscle activates, via neuronal NK2 receptors, inhibitory non-adrenergic
      non-cholinergic motorneurons. Thus, neuronal NK2 receptors should be considered
      as targets for endogenous tachykinins in enteric circuitries leading to
      descending relaxation in guinea-pig colon.

PMID- 8552257
TI  - Lack of evidence for P2X-purinoceptor involvement in fast synaptic responses in
      intact sympathetic ganglia isolated from guinea-pigs.
AB  - Recordings were made from neurons in intact pre- and paravertebral guinea-pig
      sympathetic ganglia using intracellular microelectrodes. Fast excitatory synaptic
      responses were evoked by stimulation of preganglionic and peripheral nerve
      trunks. Suramin (0.1-1 mM) did not affect passive or active membrane properties,
      nor the amplitude or decay time-course of either synaptic potentials or synaptic
      currents. Synaptic responses were reversibly reduced in amplitude by
      hexamethonium (98.7 +/- 0.8%, 50-1000 microM) and d-tubocurarine (95.3 +/- 2.6%,
      10-280 microM). ATP (0.5-1 mM) and alpha,beta-methylene ATP (1-40 microM) applied
      in the bathing solution produced no significant changes in resting membrane
      potential or input resistance. Prolonged application (up to 25 min) of either
      compound was also without effect on synaptic responses. These substances also did
      not affect ganglion cells axotomized one to five days in vivo. These data suggest
      that activation of P2X-purinoceptors is not involved in the generation of fast
      excitatory synaptic responses in intact guinea-pig sympathetic ganglia. It
      appears that dissociation of these neurons must markedly increase their
      sensitivity to purine nucleotides.

PMID- 8552258
TI  - The effect of somatosensory stimulation on second-order and efferent vestibular
      neurons in the decerebrate decerebellate guinea-pig.
AB  - The extracellularly recorded activity of medial vestibular nucleus neurons and
      efferent vestibular neurons was analysed in the decerebrate decerebellate guinea
      pig. Neurons were identified by means of electrical stimulation of the anterior
      semicircular canal. Thirty-six neurons were monosynaptically activated during
      semicircular canal stimulation. These cells were regarded as second-order
      vestibular neurons. Thirty neurons were antidromically activated and therefore
      identified as efferent vestibular neurons. Both types of neurons investigated had
      spontaneous impulse activity. All neurons responded to sinusoidal roll tilt. All
      the second-order vestibular neurons were excited during ipsilateral tilt and
      inhibited by contralateral tilt. Eighteen efferent vestibular neurons also showed
      this pattern, while the remaining 12 were excited by contralateral tilt and
      inhibited by ipsilateral tilt. Some neurons responded to passive forelimb
      extension or pressure of the forelimb plantar surface; none of the neurons
      responded to passive forelimb flexion or light plantar touch. Eleven second-order
      neurons (30%) were excited by somatosensory stimuli, seven (20%) were inhibited
      and 18 (50%) showed no response. Twenty efferent neurons (67%) were excited by
      somatosensory stimuli, none were inhibited and 10 (33%) showed no response. The
      responses of vestibular neurons to somatosensory stimulation are discussed with
      respect to their importance in vestibulospinal control during locomotion.

PMID- 8552259
TI  - The primary afferent pathway of extraocular muscle proprioception in the pigeon.
AB  - Recent physiological experiments in our laboratory suggest that extraocular
      muscle proprioceptive signals are involved in oculomotor control in the pigeon
      [e.g., Knox and Donaldson (1993) Proc. R. Soc. Lond. B 253, 77-82]; the present
      results provide information about the primary afferent pathway involved in these
      actions. In other physiological experiments [Hayman et al. (1993) Proc. R. Soc.
      Lond. B 254, 115-122] we have shown that extraocular muscle afferent signals
      modify vestibularly driven neck reflexes in the pigeon; the present results
      suggest an anatomical substrate for these effects. The localization of the cell
      bodies and of the central terminations of afferent fibres from the extraocular
      muscles of the pigeon was examined using transport of horseradish peroxidase. The
      results showed that primary afferent cell somata subserving extraocular muscle
      proprioception are located within the ipsilateral trigeminal ganglion. The
      presence of heavily labelled brainstem neurons reported in a previous study [Eden
      et al. (1982) Brain Res. 237, 15-21] was confirmed; however, these cells were
      shown to be accessory abducens motoneurons innervating the quadratus muscle, and
      presumably the pyramidalis muscle also, and not proprioceptive afferent somata as
      had been suggested. The central projections of extraocular muscle afferent
      neurons were found consistently in a restricted area of the external cuneate
      nucleus. This is in contrast to findings in a number of mammals in which the
      terminal label has been seen to cluster in portions of the spinal trigeminal
      nucleus. The presence of a lateral trigeminal tract in the pigeon, through which
      the afferent axons course, which terminates exclusively in the ventral portion of
      the external cuneate nucleus may explain this finding.

PMID- 8552260
TI  - Inflammation modulates the contribution of receptor-subtypes to bradykinin
      induced hyperalgesia in the rat.
AB  - While B2 receptors mediate pain and hyperalgesia induced by bradykinin, in normal
      rats, recent reports indicate that, in the setting of inflammation, B1 receptors
      also mediate pain and hyperalgesia. Since bradykinin-induced hyperalgesia in
      normal rats is mediated by prostaglandins released from the postganglionic
      sympathetic neurons, we have evaluated the contribution of the sympathetic
      nervous system to the hyperalgesia induced by bradykinin, a preferential B2
      receptor agonist, and des-Arg9-bradykinin, a major metabolite of bradykinin and a
      selective B1-receptor agonist. Mechanical hyperalgesia was quantified by the
      Randall-Selitto paw-withdrawal method. Inflammation was induced by injecting
      Complete Freund's Adjuvant into the left hindpaw of the rat and testing
      mechanical nociceptive threshold in the right hindpaw after injecting B1 or B2
      agonists and/or antagonists. Sympathectomy was achieved by surgically removing
      sympathetic ganglia L1-L4. Rats were used 48 h post-adjuvant injection. In the
      normal rat, intradermal injection of bradykinin but not des-Arg9-bradykinin, into
      the dorsal surface of the hindpaw, produced a dose-dependent decrease in
      mechanical nociceptive threshold. NPC 17731, a B2-receptor antagonist, but not
      des-Arg9-[Leu8]-bradykinin, a B1-receptor antagonist, almost completely inhibited
      the decrease in mechanical threshold, suggesting that bradykinin hyperalgesia in
      the normal rat hindpaw was mediated by B2 receptors. In rats whose left paws were
      treated, 48 h earlier, with adjuvant, intradermal injection of bradykinin or des
      Arg9-bradykinin, into the right paw produced dose-dependent hyperalgesia.
      Bradykinin hyperalgesia was partially inhibited by NPC 17731, and the residual
      part by des-Arg9,[Leu8]-bradykinin. des-Arg9-bradykinin hyperalgesia was
      inhibited by des-Arg9,[Leu8]-bradykinin but not by NPC17731. These results
      suggest that in the setting of inflammation, bradykinin hyperalgesia was mediated
      by both B1 and B2 receptors, and that des-Arg9-bradykinin hyperalgesia was
      mediated by the B1 receptor. Forty-eight hours after injection of complete
      Freund's adjuvant, in sympathectomized rats, bradykinin or des-Arg9-bradykinin
      failed to produce hyperalgesia, suggesting that intact sympathetic postganglionic
      neurons are required for the hyperalgesia produced by these agents in this model.
      These results are consistent with the suggestions that B2 receptors mediate
      bradykinin-induced cutaneous hyperalgesia in the normal rat hindpaw. The
      hyperalgesia induced by bradykinin, 48 h post injection of complete Freund's
      adjuvant is mediated by both B1 and B2 receptors, that by des-Arg9-bradykinin is
      mediated by B1 receptors. The hyperalgesia induced by both agents is dependent on
      the presence of intact sympathetic postganglionic neurons.

PMID- 8552261
TI  - [Importance of ischemic heart disease in patients with carotid arteriosclerosis
      and lower extremity arteriopathy. Results of a prospective study].
AB  - OBJECTIVES: Myocardial ischemia (MI) is a frequent cause of morbility and
      mortality in patients with carotid atherosclerosis (CA) independently of the
      symptomatology. The objective of our study was the identification of MI through
      clinical-history or as revealed by the stress test. METHODS: The study considered
      a consecutive series of patients with significant CA (stenosis > or = 50%),
      studied with echo-B mode and Doppler velocity scans chosen from all patients in
      the diagnostic vascular cerebral laboratory, between May 1992 and January 1994,
      for a non invasive study of neck arteries. The protocol of the multidisciplinary
      study included: history of risk factors (RF); neurologic evaluation; peripheral
      vascular evaluation with Doppler velocity scans; cardiac evaluation, and patients
      without clinical history of MI underwent a maximal stress test (ST). If there was
      bilateral carotid occlusion or non-evaluated ST the patients underwent echo
      stress with dipyridamole (ED) or myocardial scintigraphy stress test (MS);
      haematologic tests, CT in patients with symptoms of cerebral ischemia;
      arteriography of epi-aortic arteries in patients with indication for carotid
      enderterectomy. RESULTS: 133 patients were studied (age 48-80). Neurologic
      symptoms were present in 67.67%; of the RF, smoke was present in 62.48%, blood
      hypertension (BH) in 58.64% and family history in 36.84%. The MI was affirmed in
      64 patients (48.12%): in 41 with clinical history, in 23 with ST. Of the 92
      patients without clinical history: 4 with bilateral carotid occlusion underwent
      ED; 3 did not undergo ST, 85 underwent ST with negative results in 50, positive
      in 21, non-evaluated in 14 who underwent ED or MS with positive results of MI in
      2. In 25% (23/92) ST revealed MI without previous history. CONCLUSIONS: The
      patients with CA have high incidence of MI and of peripheral artery disease
      (PAD), in MI could be studied by ST. Age, smoke, BH, contribute substantially to
      the development of CA. PAD develops similarly to CA. MI is distributed
      independently of the severity of CA. A patient with CA, whatever his
      presentation, must be studied to reveal an eventual, latent or silent MI. It is
      this, in fact, which heavily conditions the prognosis.

PMID- 8552262
TI  - [Ultrasonic evaluation of early atherosclerotic damage in patients with type 1
      diabetes mellitus].
AB  - The aim of this study was to evaluate the influence of metabolic control on the
      development of atherosclerotic lesions in type 1 insulin-dependent diabetic
      patients (IDDM). MATERIALS AND METHODS: Twenty-eight well controlled IDDM
      patients, without known risk factors or clinical evidence of cardiovascular
      disease, together with 28 age-matched healthy controls spontaneously underwent
      high-resolution echographic evaluation of carotid femoral arteries. A global
      score of atherosclerotic damage as been assigned to the four investigated vessels
      on the basis of 1-6 scale, which takes into account most important ultrasound
      atherosclerotic lesion found in every artery. RESULTS: Diabetic and healthy
      controls differed significantly as regard to medio-intimal carotid thickness (p <
      0.001), but were similar as for score of atherosclerotic damage. CONCLUSIONS: Our
      results suggest that, in spite of a carotid wall medio-intimal thickness more
      pronounced in IDDM patients, well controlled IDDM is associated with
      atherosclerotic damage almost identical to that of healthy age-matched controls.

PMID- 8552263
TI  - [Reliability of clinical parameters in the diagnosis of pulmonary thromboembolism
      at an emergency department].
AB  - BACKGROUND: Pulmonary thromboembolism (PTE) mortality rate is four times greater
      among non-diagnosed than among diagnosed and hence suitably treated patients.
      Diagnosis, however, may be difficult due to the aspecific and polymorphic
      clinical picture of the disease. OBJECTIVE: We made a comparison between two
      groups of patients with PTE. In the first group the diagnosis was immediately
      suspected, in the second group it was delayed. The aim of our work was to
      identify any clinical or laboratory feature which may be helpful (singularly or
      jointly considered) to immediately recognize PTE in the Emergency Department.
      MATERIALS AND METHODS: 62 patients with PTE were studied retrospectively in 5
      consecutive years. They came to E.D. because of symptoms and signs of
      cardiorespiratory failure. Pulmonary embolism was demonstrated in 60 cases by
      high probability pulmonary scan; in 2 cases (who suddenly died after the first
      visit) by autopsy. They were divided in two groups according to the first
      provisional diagnosis made after the first visit: group A (n 33 = 53.2%) with
      assumed pulmonary embolism; group B (n 29 = 46.8%) with other diagnosis. History,
      clinical findings, ECG, chest X-ray, blood gas analysis and routine laboratory
      tests were then compared between group A and group B patients. RESULTS: No
      differences were observed between diagnosed and non-diagnosed patients, except
      for a significantly higher rate of clinically overt deep venous thrombosis in
      group A. Three main clinical pictures were detected among our patients: 1
      circulatory collapse syndrome: n = 20 (32.3%), of whom 8 in group A and 12 in
      group B (p = n.s.); 2-pulmonary infarction syndrome: n = 12 (19.4%), of whom 5 in
      group A and 7 in group B (p = n.s.); 3-uncomplicated embolism syndrome: n = 30
      (48.4%), of whom 20 in group A and 10 in group B (p = n.s.). CONCLUSIONS: In our
      study, history and signs of deep vein thrombosis were the only clues
      significantly more represented in early diagnosed cases. The possibility of
      thromboembolic accident should never be dismissed, even despite lack of a proven
      emboligenous cause in patients with unexplained chest pain or cardiorespiratory
      failure.

PMID- 8552264
TI  - [Anastomotic pseudoaneurysm, true para-anastomotic aneurysm and recurrent
      aneurysm following surgery for abdominal aortic aneurysm. Is a unifying theory
      possible?].
AB  - BACKGROUND. Recurrent aneurysms (RA) and true para-anastomotic aneurysms (TPA)
      are currently reported as anecdotal findings during occasional follow-up of
      subjects previously operated for abdominal aortic aneurysm (AAA). In several
      instances concomitant false anastomotic aneurysms (FAA) are found, not
      attributable to infection nor to suture or graft degradation. PURPOSE. To discuss
      the possibility that RA of inborn arteries, TPA, and non infectious FAA, when
      concomitantly present in the same subject, may reflect a peculiar late
      presentation of multiarterial aneurysmal disease. MATERIAL. Three cases of
      occasionally discovered concomitant RA, TPA, and FAA in subjects previously
      operated for AAA are reported. The finding of new aneurysms and FAA in subjects
      previously operated for AAA may be theoretically justified by the currently
      recognized pathogenetic mechanisms, molecular, enzymatic or genetically
      determined, implicated in the formation of AAA. This points out the need for a
      correct surgical management of AAAs and for accurate accomplishment of follow-up
      programmes supported by ultrasound echography of graft-arterial anastomoses and
      of the arteries at risk of aneurysmal disease.

PMID- 8552265
TI  - Aneurysmal form of aortoarteritis with aberrant right subclavian artery:
      diagnosis by Magnetic Resonance Angiography.
AB  - Magnetic Resonance Angiography is rapidly advancing as an important imaging
      modality for vascular disorders. With increasing experience, it bids fair to
      replace catheter angiography as the diagnostic procedure of choice in select
      clinical conditions. We report a case of aneurysmal aortoarteritis with renal
      failure, in which magnetic resonance angiography proved to be a valuable
      substitute for conventional studies. In addition, the right subclavian artery had
      an aberrant origin, an unusual association.

PMID- 8552266
TI  - [Cardiac effects of carbamazepine therapy].
AB  - The authors describe the case of an epileptic patient in chronic therapy with
      carbamazepine, and with plasma concentration of the drug in therapeutical range,
      who suffers from persistent sinus tachycardia. At the present time the
      observations available in the literature on cardiac toxicity of carbamazepina
      concern the appearance of sinus tachycardia as consequence of overdose and of
      blocks of conduction in elderly with carbamazepine in therapeutical range.

PMID- 8552267
TI  - [An unusual case of "catecholamine necrosis" caused by accidental digitalis
      poisoning].
AB  - Toxic manifestations of digitalis are one of the most prevalent adverse drug
      reactions encountered in clinical practice. The estimated incidence is about 20%
      in hospitalized patients in the USA. The authors describe a rare case of
      myocardial "catecholamine necrosis" (anteroseptal myocardial infarction) during
      accidental digitalis intoxication. A male patient, 75 years old, suffering from
      cirrhosis and ascites, take on by mistake a tablet of digoxin 0.25 mg. four times
      at day for eleven days. He hadn't heart disease in the past. At the eleventh day
      the patient showed a deep tiredness and so he was submitted to a clinical
      examination and electrocardiogram. The ECG demonstrated an anteroseptal
      myocardial infarction in the second-third electrical stage. The patient was
      hospitalized. The successive examination revealed: very high plasma digitalis
      concentrations; an increase of the serum levels of CPK and LDH; a significant
      increase of plasmatic and urinary catecholamine levels which return to normal
      values after fifteen days; apical akinesia at the echocardiographic examination;
      no signs of residual myocardial ischemia to the echo-dypiridamole stress test;
      normal coronary artery to the coronary arteriography and absence of coronary
      artery spasm to the ergonovine test. Furthermore the abdominal echography and the
      abdominal computerized tomography didn't reveal surrenal disease but showed an
      important liver disease. The patient was free from other cardiac events in the
      follow-up. Generally, during the digitalis intoxication we observe various rhythm
      and conduction disturbances. Instead in this case no serious arrhythmias were
      registered and the main expression of the drug toxicity was an anteroseptal
      myocardial infarction with undamaged coronary artery. Also the usual extracardiac
      symptoms and signs of the digitalis intoxication were absent in this case. All
      these observations can be explained with the pathological increase of the
      cathecholamine levels, indirectly induced by digitalis; with the direct toxic
      effect of the drug at the myocardic level; with the contemporary absence of ionic
      disturbances; with the concomitant liver disease. The direct toxic effect of the
      digitalis produced an increase in calcium ions availability for the
      electromechanical coupling and an increase of the intramyocardial pressure; the
      increase of the adrenergic activity determined contemporary an increase in the
      oxygen consumption of the myocardial cells, a rise of vascular tone and coronary
      artery tone and a reduction of the duration of the diastole. All these factors
      provoked a "primary and secondary" ischemia which evolved toward a real
      "cathecholamine necrosis" and produced a myocardial infarction. This hypothesis
      explains the myocardial infarction in absence of injury at the coronary
      arteriography and without coronary spasm at the ergonovine test; moreover it
      explains the transient increase in cathecholamine plasma levels observed in the
      acute phases an normalized after fifteen days. The "cathecholamine necrosis" is
      an anatomical definition, nevertheless in our opinion it gives account of the
      rare clinical situation observed.

PMID- 8552268
TI  - [Comparison of metabolic and hemodynamic effects of hydrochlorothiazide in
      monotherapy and in association with lisinopril. An Italian multicenter study].
AB  - The aim of this study was to evaluate the metabolic effects of the treatment with
      hydrochlorothiazide 25 mg/die monotherapy and with the association of lisinopril
      20 mg + HCT2 12.5 mg/die in patients with mild to moderate arterial hypertension,
      in addition to antihypertensive efficacy and tolerability. For this aim 669
      hypertensive patients have been randomized in a double blind, parallel study to
      the monotherapy or to the association. The follow-up was of 12 weeks, after a run
      in wash-out period of 3-4 weeks. Seated blood pressure and heart rate were
      measured in all 4 outpatients visit and blood was withdrawn for serum
      electrolytes, glycemia, serum creatinine, uric acid and lipoprotein profile. 338
      patients were randomized to the association and 331 to monotherapy with a slight
      prevalence of women. Mean age (58 +/- 9 and 56 +/- 10 years), pretreatment seated
      blood pressure (165 +/- 14/102 +/- 5 and 166 +/- 15/105 +/- 5 mmHg) and heart
      rate (77 +/- 9 heart/min in both group) were similar in the two groups. Seated
      blood pressure was significantly reduced in both groups (-22.8/-16.8 mmHg in the
      association group and -18.8/-13.4 mmHg in the monotherapy group), however the
      blood pressure reduction in patients treated with the association was slightly,
      but significantly, greater. Lipid profile, blood glucose, serum potassium and
      creatinine and uric acid were slightly worsened in the monotherapy group, while
      there were no changes or a mild improvement in patients treated with the
      combination of diuretic and the ACE-inhibitor. In conclusion the association
      lisinopril 20 mg+hydrochlorothiazide 12.5 mg/die causes a blood pressure
      reduction slightly, but significantly, greater than with a higher dose of the
      diuretic monotherapy, without any negative interference on lipid profile, blood
      glucose and serum potassium.

PMID- 8552269
TI  - [Nationwide drug surveillance project on slow-release nicardipine in the short
      term therapy of light/moderate arterial hypertension].
AB  - This trial was designed to confirm the hypotensive action and safety of slow
      release nicardipine, as a single drug or together with other hypotensive drugs,
      for the short-term treatment of mild-to-moderate hypertension, on a large case
      list of patients in 57 centers throughout Italy. A total of 1011 patients (502 M,
      509 F) were admitted, mean age 58.6 +/- 9.1 years (range 25-87), mean weight 72.7
      +/- 11.1 kg (range 43-128), with essential (972 cases) or secondary hypertension
      (39 cases). Nicardipine was given orally at a mean daily dosage of 80 mg (range
      40-120), for four weeks. Clinically and statistically significant reductions in
      systolic and diastolic BP were observed at the end of treatment, with no
      noteworthy changes in heart rate. Nicardipine single-drug therapy restored normal
      blood pressure in 79.7% of patients with essential hypertension, and in 72.0% of
      those with secondary hypertension; nicardipine associated with other hypotensive
      agents achieved normal blood pressure in respectively 65.9% and 42.9%. Blood
      pressure returned to normal in 77.3% of patients with essential hypertension aged
      65 years or under, and in 66.9% of those over 65 years old. These figures were
      respectively 70.8% and 46.7% for patients with secondary hypertension. The
      treatment was very well tolerated by 86.2% of patients; 140 (13.8%) presented
      adverse reactions, requiring dose reductions in 12, and discontinuation of
      treatment only in 24 cases. Five patients taking nicardipine together with
      another drug presented adverse reactions. These results confirm that slow-release
      nicardipine is effective and extremely well tolerated in the treatment of mild-to
      moderate essential or secondary hypertension, in adults and the elderly.

PMID- 8552270
TI  - Increased cortical nuclear factor-kappa B (NF-kappa B) DNA binding activity after
      traumatic brain injury in rats.
AB  - Nuclear factor-kappa B (NF-kappa B) DNA binding factor is an inducible
      transcription factor that responds to various cellular signals. Levels of
      cortical NF-kappa B DNA binding activity were measured in a controlled lateral
      cortical impact model of traumatic brain injury (TBI) in rats. Using
      electrophoretic mobility shift assays (EMSAs), we found that NF-kappa B DNA
      binding activity in cerebral cortex ipsilateral to the injury site increased at
      1, 3, 5 and 7 days after injury. Binding activity peaked at 3 days after injury
      and subsided by 10 days after injury. These data indicate that TBI produces
      transient increases in NF-kappa B DNA binding activity. Further insights into the
      role of NF-kappa B in TBI may provide new therapeutic opportunities for head
      trauma.

PMID- 8552271
TI  - Chronic ethanol administration decreases brain-derived neurotrophic factor gene
      expression in the rat hippocampus.
AB  - We have previously demonstrated that chronic ethanol consumption decreases
      neurotrophic activity in hippocampal extracts, as assessed by a chick dorsal root
      ganglia bioassay, but has no effect on hippocampal NGF mRNA or NGF protein
      levels. We presently report that hippocampal mRNAs encoding neurotrophin-3 and
      basic fibroblast growth factor are also unaffected. However, in contrast, brain
      derived neurotrophic factor mRNA is reliably decreased, thereby suggesting that
      ethanol-induced damage of the septohippocampal system may at least partially
      result from an ethanol-induced decrease in hippocampal brain-derived neurotrophic
      factor expression.

PMID- 8552272
TI  - Clomethiazole protects the brain in transient forebrain ischemia when used up to
      4 h after the insult.
AB  - Brief periods of forebrain ischemia result in consistent damage in the
      hippocampus in gerbils. This damage can be attenuated by free radical scavengers,
      glutamate antagonists and GABA agonists. Most of the work with cerebral
      protection has been done with agents infused prior to the insult. In this
      experiment we tested clomethiazole, a GABA agonist, as a neuroprotective agent 1
      and 4 h after a 5 min ischemic insult (bilateral carotid occlusion) in gerbils.
      Damage was assessed using silver staining techniques at 7 days after the insult.
      There were 10 animals in each group. Clomethiazole was given subcutaneously at a
      dose of 100 mg/kg. Compared to controls, there was significant protection in the
      CA1 (P < 0.01) and CA4 (P < 0.01) regions of the hippocampus at 1 and 4 h after
      the ischemic insult. GABAergic agents may play an important role in neuronal
      protection when used after ischemic insults.

PMID- 8552273
TI  - Serotonergic cells in nucleus raphe pallidus provide tonic drive to posterior
      cricoarytenoid motoneurons via 5-hydroxytryptamine2 receptors in cats.
AB  - Microinjection of serotonin and 5-hydroxytryptamine2 (5-HT2) agonist 1-(2,5
      dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in nucleus ambiguus caused
      excitation of posterior cricoarytenoid (PCA) muscles of the larynx in
      anesthetized, spontaneously breathing cats. Intravenous administration of 5-HT2
      antagonist ketanserin produced complete block of excitatory effect of DOM
      injection. Electrical stimulation of nucleus raphe pallidus caused excitation of
      PCA activity, that was blocked by pretreatment of ketanserin. These results
      indicate that serotonergic cells in the raphe pallidus provide tonic drive to
      medullary PCA motoneurons through 5-HT2 receptors.

PMID- 8552274
TI  - Synaptic organization and ultrastructural features of the substance P-receptor
      like immunoreactive neurons in the nucleus intermediolateralis of rats.
AB  - Synaptic and ultrastructural organization in the intermediolateral nucleus (IML)
      of rat were investigated with electron microscopy combined with pre-embedding
      immunohistochemistry for substance P (SP)-receptor (SPr). SPr immunoreactivity in
      IML was found in the vicinity of the cellular membrane of the perikarya and
      dendritic profiles of the small sized neurons, ranging from 15 to 25 microns in
      length. A SPr-immunoreactive (SPr-ir) soma had symmetric or asymmetric synaptic
      contacts with three to five unlabeled axon terminals. Two different types of axon
      terminals made synapses on the SPr soma, one contained 20-30 nm pleomorphic
      vesicles and large dense cored vesicles and the other contained clear pleomorphic
      vesicles of 30-50 nm in size. Occasionally, SPr-ir dendrites are very closely
      apposed to the blood capillary. Our present results suggested the possibility
      that the IML SPr-ir neurons might be activated by several kinds of synaptic
      inputs and SP provided from blood flow.

PMID- 8552275
TI  - Differential regulation of C3 gene expression in human astroglioma cells by
      interferon-gamma and interleukin-1 beta.
AB  - In this report, we examined interferon-gamma (IFN-gamma) and interleukin-1 beta
      (IL-1 beta)-mediated regulation of the expression of C3, the third component of
      complement, in a human astroglioma cell line. Interleukin-1 beta induced C3
      protein expression ten-fold more rapidly than IFN-gamma. De novo protein
      synthesis was required for IFN-gamma to stimulate C3 expression, while
      cycloheximide and IL-1 beta treatment of cells markedly increased C3 expression.
      Actinomycin D, inhibited C3 gene induction by IFN-gamma and IL-1 beta suggesting
      that these cytokines act, in part, at the transcriptional level to enhance C3
      expression. Understanding cytokine-mediated regulation of complement gene
      expression in the astrocyte is important in defining the role of these molecules
      in CNS inflammation and autoimmune diseases.

PMID- 8552276
TI  - Increasing background inspiratory resistance changes somatosensory sensations in
      healthy man.
AB  - The central purpose of the study was to investigate if increasing background
      inspiratory resistance, a circumstance which activated afferents from the lungs
      and respiratory muscles, modified somatosensory and/or auditory sensations in
      healthy individuals. Estimation of mechanical stimulations applied on the middle
      finger (somatosensory sensation) and unilateral sound-pressure stimulations
      (auditory sensation) was based on the computation of Stevens' power function psi
      = k.phi n, where psi is the estimate and phi is either the somatosensory stimuli
      or sound-pressures. This was studied during eupnoeic unloaded ventilation then
      during a 10-min period of loaded breathing followed by a 10-min recovery period.
      Loaded breathing significantly lowered the estimate of somatosensory stimuli
      (decreased n coefficient). This effect persisted during the two first minutes of
      recovery period. By contrast, loaded breathing did not modify the perception of
      auditory stimulus. As somesthetic and respiratory afferents, but not auditory
      afferents, project on the same area in the sensory cortex we suggest the
      existence of central interactions which could explain observations of the
      difficulties to execute accurate tasks in patients suffering from obstructive
      lung disease independently from the alterations in their arterial blood gases.

PMID- 8552277
TI  - Hypoxemia does not affect the strength of the inspiration-inhibiting Breuer
      Hering reflex.
AB  - Several studies were focused on the consequences of reduced PaO2 (hypoxemia) on
      the Breuer-Hering inspiration-inhibiting vagal reflex. However, these data are
      often contradictory and do not allow us to decide whether hypoxemia interacts
      with the central integration of pulmonary vagal afferents and/or exerts
      peripheral influence on pulmonary stretch receptor (PSR) activity. The present
      study was performed in anesthetized rabbits breathing different gas mixtures
      containing O2, N2 and CO2. Intravenous injection of bicarbonates and CO2 addition
      in the inspired mixture maintained pHa and PaCO2 within their physiological
      ranges. The Breuer-Hering reflex, assessed from the changes in diaphragmatic EMG
      activity, was elicited either by inflating the lungs at different volumes above
      the functional residual capacity (PSR activation) or by direct electrical
      stimulation of vagal afferents (central stimulation). Hypoxemia never
      significantly modified the strength of the reflex or its threshold. Thus, acute
      hypoxemia present at high altitude does not seem to modify the key role played by
      PSR afferents in the ventilatory control.

PMID- 8552278
TI  - Open-loop and closed-loop postural control mechanisms in Parkinson's disease:
      increased mediolateral activity during quiet standing.
AB  - Stabilogram-diffusion analysis was used to gain insights into how idiopathic
      Parkinson's disease (IPD) affects the postural control mechanisms involved in
      maintaining erect stance. Twenty-two subjects with IPD and twenty-four healthy
      elderly subjects were studied under eyes-open, quiet-standing conditions. The
      postural control mechanisms in the parkinsonian subjects, compared to the healthy
      elderly, were characterized by an increase in the effective stochastic activity
      in the mediolateral direction. Mediolateral posturographic measures were also
      associated with a history of falls and poor performance on clinical measures of
      balance. It is hypothesized that the increase in mediolateral activity in
      subjects with IPD may reflect an attempt to maintain potentially stabilizing
      movements during quiet standing in the face of impaired movement in the
      anteroposterior direction. This study supports the notion that mediolateral
      instability is an important posturographic marker of functional balance
      impairment in the elderly.

PMID- 8552279
TI  - Pain-related cerebral potentials in patients with frontal or parietal lobe
      lesions.
AB  - The present study investigated the processing of painful electrical stimuli in
      patients with unilateral frontal or parietal lobe damage and matched control
      subjects. Patients with frontal lesions showed increased pain thresholds when the
      stimuli were administered contralateral to the lesion. While the peak-to-peak
      amplitudes of the N150/P250 components of the somatosensory potentials increased
      linearly with stimulus intensity in the control subjects, the responses in the
      frontal group did not change significantly between stimulation at pain and
      tolerance threshold. There was no evidence for altered pain processing in
      patients with parietal lobe lesions. The findings of the present study support
      the hypothesis of an involvement of the frontal cortex in pain perception in
      humans.

PMID- 8552280
TI  - Muscarinic depression of excitatory synaptic transmission mediated by the
      presynaptic M3 receptors in the rat neostriatum.
AB  - The effect of carbachol on the excitatory synaptic transmission was studied in
      rat neostriatal neurons using intracellular and whole-cell voltage clamp
      recording methods. Depolarizing excitatory postsynaptic potentials (EPSPs) were
      evoked by cortical stimulation. Superfusion of carbachol (0.01-3 microM)
      reversibly decreases the EPSP amplitude in a concentration-dependent manner and
      with an estimated IC50 of 0.3 microM. While, neither the N-methyl-D-aspartate
      (NMDA, 100 microM)- nor (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic
      acid (AMPA, 100 microM)-induced response was affected by carbachol (0.1 microM).
      In addition, the inhibitory effect induced by carbachol at a low concentration of
      0.1 microM was attenuated by 4-diphenylacetoxy-N,N-methyl-piperidine (4-DAMP), a
      selective M3 muscarinic receptor antagonist. However, other muscarinic subtype
      (M1 or M2) antagonists could also block the inhibitory effect by carbachol 0.1
      microM. The rank order of antagonist potency was: 4-DAMP (M3 antagonist) >
      methoctramine (M2 antagonist) > pirenzepine (M1 antagonist). Based on these
      findings, we conclude that carbachol at a low concentration (< or = 0.1 microM)
      reduced the excitatory response of neostriatal neurons following cortical
      stimulation via presynaptic M3 muscarinic receptors located on the terminals of
      corticostriatal neurons.

PMID- 8552281
TI  - Neurogenesis is absent in the brains of adult honey bees and does not explain
      behavioral neuroplasticity.
AB  - The mushroom bodies, the insect brain structures most often associated with
      learning, exhibit structural plasticity during adult behavioral development in
      honey bees. We have investigated whether adult neurogenesis contributes to the
      plasticity of the mushroom bodies by labeling the DNA of replicating cells with 5
      bromo-2'-deoxyuridine (BrdU). Immunocytochemical analysis of brain sections from
      bees fed or injected with BrdU as well as from bees treated in vitro with BrdU
      revealed no labeled neuronal nuclei, regardless of age or behavioral status of
      the worker bee (1-day old, nurse, or forager). Our results demonstrate that
      neurogenesis in the adult bee brain is a rare event, if it occurs at all.
      Therefore, the structural changes observed in the bee brain during adult
      behavioral development must be explained by developmental processes other than
      neurogenesis.

PMID- 8552282
TI  - Glycogen synthase kinase-3 beta phosphorylates tau protein at multiple sites in
      intact cells.
AB  - Hyperphosphorylated tau protein is the major constituent of the paired helical
      filament (PHF), the major fibrous component of the neurofibrillary lesions of
      Alzheimer's disease (AD). Hyperphosphorylation of tau is believed to be the
      critical event that leads to filament assembly. Identification of the responsible
      protein kinases is therefore a key step towards an understanding of the
      pathogenesis of AD. Mitogen-activated protein kinase, glycogen synthase kinase-3
      (GSK3) and neuronal cdc2-like kinase have been shown to phosphorylate tau protein
      in vitro at a number of sites that are phosphorylated in PHFs. In this study, we
      report that transient transfection of human GSK3 beta into Chinese hamster ovary
      cells stably transfected with individual human tau isoforms leads to
      hyperphosphorylation of tau at all the sites investigated with phosphorylation
      dependent anti-tau antibodies. Thus, GSK3 beta is a protein kinase that
      phosphorylates tau protein in intact cells.

PMID- 8552283
TI  - Comparison of [125I]iodomelatonin binding sites in infant cerebellum of sudden
      infant death syndrome and non-sudden infant death syndrome.
AB  - [125I]Iodomelatonin bindings sites in human infant cerebellum were studied by
      radioligand receptor binding assay and in vitro quantitative autoradiography. The
      binding sites characterized in membrane preparations revealed saturable,
      reversible and highly specific binding sites with a Kd value of 21.2 +/- 8.33 pM
      and a Bmax value of 2.02 +/- 0.52 fmol/mg protein. 10 microM of GTP gamma S
      significantly reduced the binding capacity, suggesting the possible G-protein
      coupling of the binding sites. Autoradiographic study showed that the labelling
      was mainly located in the cerebellar cortex. On comparison of the binding
      parameters from cerebellum of sudden infant death syndrome (SIDS) and non-SIDS
      infants, no significant change in binding capacity and binding affinity was
      detected. These findings suggest that the binding sites in cerebellum may not be
      related to the etiology of SIDS.

PMID- 8552284
TI  - Time course of neurofilament protein loss following depolarization-induced injury
      in CNS culture.
AB  - In septo-hippocampal cell cultures, brief potassium depolarization produces
      calcium-dependent decreases in neurofilament proteins and loss of fine neuritic
      processes within 24 h. It is not known whether neurons later exhibit delayed
      degeneration and die, live with enduring neurofilament loss, or restore
      neurofilament protein levels. Therefore, we exposed septohippocampal cultures to
      6 min potassium depolarization (60 mM) with 2.8-11.8 mM extracellular Ca2+ and
      evaluated immunoreactivity for low, medium and heavy neurofilament proteins,
      neuronal number, and neuronal morphology for 10 days. Neuronal number remained
      unchanged; neurofilament protein levels recovered to between 31% and 99% of
      control levels, and fine neuritic processes reappeared.

PMID- 8552285
TI  - Whole-cell analysis of NGK2 (mKv3.1a) K+ channels stably expressed in mouse
      fibroblast cells.
AB  - NGK2 (mKv3.1a) K+ channel cDNA was introduced into mouse B82 fibroblast cells to
      express in a mammalian system. The NGK2 current in the stably transformed
      fibroblast cells exhibited a high threshold for activation and slow decay with
      two components. The data suggest that the NGK2 channel may contribute to slowly
      inactivating K+ currents observed in excitable and inexcitable cells.

PMID- 8552286
TI  - Detection of hydroxyl radicals in rat striatum during transient focal cerebral
      ischemia: possible implication in tissue damage.
AB  - As increasing arguments suggest that the reperfusion phase following an ischemic
      insult may aggravate tissue injury by yielding hydroxyl radicals ('OH), we
      examined whether these oxyradicals are generated in rat striatum during transient
      focal cerebral ischemia. .OH were detected in dialysate samples by intrastriatal
      microdialysis coupled with the technique of salicylate hydroxylation. Ischemia
      was achieved by tandem occlusion of the left middle cerebral artery and common
      carotid arteries (45 min) followed by reperfusion. An .OH formation occurred both
      during ischemia and early reperfusion. Additionally, the volume of the striatal
      infarct induced by ischemia correlated positively with the amount of .OH produced
      during ischemia and reperfusion. Taken together, these results provide evidence
      of the formation of cytotoxic .OH in rat striatum which might participate in the
      ischemic injury of this structure.

PMID- 8552287
TI  - Na+,K(+)-ATPase activities are increased in brain in both congenital and acquired
      hyperammonemic syndromes.
AB  - Activities of Na+,K(+)-ATPase were measured in brain regions of experimental
      animals with either congenital or acquired hyperammonemia. In the sparse-fur
      (spf) mutant mouse, with a genetic X-linked deficiency of ornithine
      transcarbamylase, an animal model of congenital hyperammonemia, Na+,K(+)-ATPase
      was increased in frontal cortex (by 57%, P < 0.001), cerebellum (by 61%, P <
      0.001), brainstem (by 71%, P < 0.001) and striatum (by 48%, P < 0.01). Four weeks
      following portacaval anastomosis in the rat, Na+,K(+)-ATPase activities were
      increased in cerebellum and striatum (by 19%, P < 0.01) and in brainstem (by 28%,
      P < 0.01). Stimulation of Na+,K(+)-ATPase and the subsequent alteration of
      neuronal excitability could contribute to the CNS dysfunction characteristic of
      chronic hyperammonemic syndromes.

PMID- 8552288
TI  - Characterization of an ultraviolet photoreception mechanism in the retina of an
      amphibian, the axolotl (Ambystoma mexicanum).
AB  - Spectral sensitivity measurements from the retina of the Mexican salamander
      Ambystoma mexicanum (the 'axolotl') were used to provide evidence for and to
      characterize an amphibian ultraviolet-sensitive photoreception mechanism.
      Electroretinograms (transretinal voltage responses) were recorded from open eye
      cup preparations to analyze the spectral sensitivity of the retina. Both dark
      adapted and white light-adapted preparations exhibited a peak in sensitivity
      between 360-370 nm. Under selective chromatic adaptation with long-wavelength
      light the eye cups continued to exhibit a peak sensitivity around 360 nm. These
      data confirm the presence of ultraviolet-sensitive cones in the retina of
      Ambystoma salamanders. The possible relevance of these results to the development
      and behavior of this group of salamanders is briefly discussed.

PMID- 8552289
TI  - Choline substitution for sodium triggers glutamate and adenosine release from rat
      hippocampal slices.
AB  - Substituting choline for sodium resulted in an extracellularly recorded transient
      depolarization and increased efflux of glutamate and adenosine from rat
      hippocampal slices. The depolarization was blocked by a combination of NMDA and
      non-NMDA antagonists, MK-801 (10 microM) and 6,7-dinitroquinoxaline-2,3-dione
      (DNQX, 50 microM). Adenosine release was blocked by MK-801 alone. These data
      suggest that glutamate released as a result of the sodium removal acts at NMDA
      and non-NMDA glutamate receptors to trigger the depolarization and acts at NMDA
      receptors to trigger adenosine release.

PMID- 8552290
TI  - A new metric for analyzing single-trial event-related potentials (ERPs):
      application to human visual P300 delta response.
AB  - Visual P300 responses were recorded by using checkerboard-type stimuli. (1) High
      amplitude P300-delta responses were visible even in single trial event-related
      potentials (ERPs). (2) The algorithm based on the 'delta response metric'
      provides an efficient selection criterion for evaluation of P300 single trials in
      ERP ensembles. (3) The 'universal' character of the P300-delta response
      demonstrated in this report may open new avenues for the understanding of
      functional ERP components.

PMID- 8552291
TI  - Peripherally injected scopolamine differentially modulates acetylcholine release
      in vivo in the young and aged rats.
AB  - The effect of intraperitoneal administration of scopolamine (1 mg/kg) on
      acetylcholine (ACh) release in vivo in 3- and 24-month-old freely behaving rats
      was investigated in the cerebral cortex, hippocampus and striatum by means of
      transverse microdialysis. In the parietal cortex, the increase in ACh release
      after scopolamine administration was significantly greater in the old than in the
      young rats, reaching a maximum increase of about 600 and 300% in the old and
      young animals, respectively. In the hippocampus, scopolamine caused a larger
      increase in ACh release in the young (+900%) than in the old rats (+600%). In the
      striatum of aged rats, a 40% increase occurred only at 40 min after scopolamine
      administration while in the striatum of young animals the increase lasted for at
      least 2 h, reaching a maximum of about 100%. These findings demonstrate that the
      modulation of ACh release in vivo is affected in a different manner in the
      cerebral cortex than in the hippocampus and striatum by aging.

PMID- 8552292
TI  - Fibroblast growth factor (FGF)-2 sense and antisense mRNA and FGF receptor type 1
      mRNA are present in the embryonic and adult rat nervous system: specific
      detection by nuclease protection assay.
AB  - In the present study, we attempted to clarify the controversial question whether
      basic fibroblast growth factor (bFGF, FGF-2) mRNA is present or absent in the
      embryonic central nervous system (CNS). For this purpose we analyzed the
      expression of the FGF-2 mRNA in the embryonic and adult forebrain, brainstem, and
      spinal cord using the highly specific ribonuclease protection assay. Using this
      method we were able to detect FGF-2 mRNA in the rat CNS of embryonic day (E) 16
      and 17, however, at lower levels compared to adult FGF-2 mRNA levels. In
      addition, we show that a FGF-2 antisense transcript is expressed in embryonic CNS
      tissue. Furthermore, using this method, we demonstrate FGF receptor 1 mRNA in the
      rat embryonic and adult CNS. The presence of FGF-2 and FGF receptor 1 suggests a
      physiological role for this growth factor during the development of the embryonic
      CNS.

PMID- 8552293
TI  - Brain-derived peptides regulate the steady state levels and increase stability of
      the blood-brain barrier GLUT1 glucose transporter mRNA.
AB  - The blood-brain barrier (BBB) GLUT1 glucose transporter gene expression is known
      to be regulated by putative brain trophic factors. Therefore, the present study
      investigated the effect of a brain-derived peptide rich preparation containing a
      neurotrophic factor-like action [Cerebrolysin (Cl), EBEWE, Austria]. In cultures
      of brain capillary endothelial cells, Cl induced a transient increase in the
      abundance of BBB-GLUT1 relative to actin measured by reverse transcription
      polymerase chain reaction during the first 2 h of incubation, whereas a
      significant reduction in the GLUT1 transcript was observed at 20 and 48 h. In
      addition, Cl abolished the fall in GLUT1 levels induced by actinomycin D. The
      present data suggest that brain-derived factors in Cl are able to modulate the
      expression of the BBB-GLUT1 gene increasing the BBB-GLUT1 transcript stability.

PMID- 8552294
TI  - Acidic fibroblast growth factor prevents post-axotomy neuronal death of the
      newborn rat facial nerve.
AB  - The death of facial motoneurons after axotomy provides a useful tool for studying
      neurotrophic factors which could prevent motoneuron loss in vivo. The right
      facial nerve trunk before the postauricular nerve branching of newborn rats was
      transected at its extracranial exit, and topically treated, at the axotomy site,
      with either a vehicle solution containing agarose or sucralfate, or acidic
      fibroblast growth factor (aFGF). Acidic FGF treatment increased the survival of
      the facial motoneurons from 18% to 70%. These results suggest that aFGF is a
      neurotrophic factor for motoneurons in vivo and that this growth factor may
      provide a new basis for the development of treatments to prevent the loss of
      damaged motoneurons.

PMID- 8552295
TI  - The expression of ornithine decarboxylase antizyme mRNA and protein in rat
      motoneurons.
AB  - The distribution of ornithine decarboxylase antizyme messenger ribonucleic acid
      (AZ mRNA) and AZ-like immunoreactivity (LI) was studied in the brainstem and
      spinal cord motoneurons and in the extraocular and triceps surae muscles of rat.
      In situ hybridization showed AZ mRNA in the gray matter of the spinal cord at
      different levels of spinal cord with highest AZ mRNA levels in the ventral horn
      of the spinal cord. No apparent changes in AZ mRNA contents were seen after
      unilateral transection of the sciatic nerve in lumbar motoneurons. AZ
      immunoreactive (IR) motoneurons were observed in the nucleus of the VI cranial
      nerve and in the ventral horn of the spinal cord. These motoneurons also showed
      ornithine decarboxylase (ODC)-LI. Subcellularly, AZ-LI was observed both in the
      nuclei and cytoplasm of labeled motoneurons. Heavily stained AZ-IR nerve fibers
      and myoneural junctions were observed among muscle fibers in different muscles.
      In addition, the nuclei of muscle fibers showed AZ-LI.

PMID- 8552296
TI  - Nitric oxide synthase inhibitor blocks acetylcholine induced increase in brain
      blood flow in rainbow trout.
AB  - Nitric oxide (NO) dependent regulation of blood flow has hitherto not been
      demonstrated in rainbow trout or other salmonid fish. Through in vivo
      observations of the brain surface (optic lobes) of rainbow trout (Oncorhynchus
      mykiss) with epi-illumination microscopy, we show that application of
      acetylcholine (ACh) to the brain surface induces an increase in cerebral blood
      flow velocity that can be completely blocked by the NO synthase inhibitor NG
      nitro-L-arginine. Also sodium nitroprusside, which decomposes to form NO,
      stimulated cerebral blood flow velocity. The results indicate that NO is a
      vasodilator in rainbow trout brain, mediating the effect of ACh.

PMID- 8552297
TI  - Modulation of hippocampal ACh release by chronic nicergoline treatment in freely
      moving young and aged rats.
AB  - The effects of nicergoline on basal and K(+)-stimulated release of ACh in the
      hippocampus of 3- and 19-month old rats has been studied by microdialysis. A
      significant decrease of basal ACh release (59%) was found in aged vehicle treated
      rats in comparison to young rats. High-K+ (100 mM) in the perfusate strongly
      increased the release of ACh by up to 6-fold over the baseline of both young and
      aged rats. Chronic oral administration of nicergoline to aged rats (5 mg/kg
      b.i.d. for 6 weeks) significantly reversed (93%) the age-related decrease of
      basal release of ACh, leaving the increase due to K+ depolarization unchanged. In
      young animals, nicergoline did not affect the basal output of ACh, but enhanced
      the K(+)-evoked release of ACh by 39%. Results from this study demonstrate that
      nicergoline treatment increases the ability of hippocampal cholinergic terminals
      to release ACh, and suggest that this drug can reset the cholinergic impairement
      associated with aging.

PMID- 8552298
TI  - Effects of nitric oxide on sympathetic baroreflex transmission in the nucleus
      tractus solitarii and caudal ventrolateral medulla in cats.
AB  - We have previously shown that nitric oxide (NO) attenuates baseline sympathetic
      tone in the rostral ventrolateral medulla (RVLM), while having no effects on
      baroreflex transmission in this region in cats. In the present study, we tested
      the effects of microinjections (500 nl) of NG-nitro-L-arginine (L-NNA, 0.3 mM) or
      the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 10 microM) in the nucleus
      tractus solitarii (NTS) and in the caudal ventrolateral medulla (CVLM) which are
      the two other relays of the sympathetic baroreflex within the brainstem. Neither
      L-NNA nor SNAP significantly changed the length of inhibition of renal
      sympathetic nerve activity (SNA) evoked by electrical stimulation of the
      ipsilateral carotid sinus nerve. In contrast, glutamate (1 mM) in the NTS
      markedly increased baroreflex inhibition of SNA and the glutamate receptor
      antagonist kynurenate (5 mM) in the CVLM significantly decreased baroreflex
      transmission in the same experiments. These results suggest that sympathetic
      baroreflex function is preserved during both impaired endogenous synthesis and
      excess exogenous supply of NO in the brainstem.

PMID- 8552299
TI  - Recombinant acetylcholinesterase has behavioural effects in the rat substantia
      nigra not attributable to its enzymatic activity.
AB  - An unexplained action of acetylcholinesterase (AChE) has previously been
      demonstrated on motor behaviour in the substantia nigra: a single infusion of the
      protein induced long-term circling behaviour, reflecting sustained increased
      activity of the nigro-striatal pathway. In this study, a highly purified form of
      AChE was infused and the long-term behavioural effects were still observed. In
      addition, recombinant human AChE produced a similar response, suggesting that
      AChE itself, and not a contaminant, was responsible for these behavioural
      actions. Butyrylcholinesterase, which also hydrolyses acetylcholine, was without
      effect. Hence AChE is not exerting these actions by potentiating the
      neurotransmitter acetylcholine, but via some cholinergic-independent mechanism.

PMID- 8552300
TI  - (RS)-alpha-Methyl-4-carboxyphenylglycine inhibits long-term potentiation only
      following the application of low frequency stimulation in the rat dentate gyrus
      in vitro.
AB  - The effect of the metabotropic glutamate receptor (mGluR) antagonist (RS)-alpha
      methyl-4-carboxyphenylglycine (MCPG) was investigated on the induction of long
      term potentiation (LTP) of alpha-amino-3-hydroxy-5- methyl-4-isoxazoleproprionate
      receptor-mediated excitatory postsynaptic currents (epscs) recorded from dentate
      granule cells in response to presynaptic stimulation of the
      associational/commissural pathway of the rat dentate gyrus in vitro. MCPG (500
      microM, 60 min) did not inhibit the induction of LTP of epscs induced by high
      frequency stimulation (HFS) at sites which had received only test stimulation
      (0.05/s) preceding the HFS. MCPG did, however, block the induction of LTP of
      epscs elicited by HFS if the HFS was preceded by the induction of long-term
      depression elicited by low frequency stimulation (5 Hz for 3 min). After such low
      frequency stimulation, HFS induced only a short-term potentiation lasting up to a
      maximum of 10 min in the presence of MCPG.

PMID- 8552301
TI  - Sulfonated dyes attenuate the toxic effects of beta-amyloid in a structure
      specific fashion.
AB  - We recently reported that several sulfate-containing glycosaminoglycans, a class
      of compounds associated with the beta-amyloid plaques of Alzheimer's disease,
      attenuate the toxic effects of beta-amyloid fragments beta 25-35 and beta 1-40.
      The amyloid-binding sulfonated dye Congo Red was shown to have a similar effect.
      Using two clonal cell lines, we now demonstrate that several sulfonated dyes
      attenuate beta-amyloid toxicity and that the protective effect appears specific
      for compounds whose sulfonate groups can interact with the beta-pleated structure
      of aggregated amyloid. These results suggest that by binding beta-amyloid these
      compounds may prevent toxic interactions of the peptide with cells.

PMID- 8552302
TI  - Neurotoxic mechanisms of transactivating protein Tat of Maedi-Visna virus.
AB  - Infection by lentiviruses such as human immunodeficiency virus (HIV) and Maedi
      Visna virus (MVV) is associated with neurodegenerative disorders. We have
      investigated the neurotoxic mechanisms of a synthetic peptide of transactivating
      protein tat of MVV in striatal neuronal cultures. Tat peptide (but not control
      peptide) caused neuronal death, without affecting glial viability, in a time- and
      dose-dependent manner. Significant neuronal death was not observed until 6-8 h
      after tat peptide application (2.35-2350 nM), whereas half maximal and maximal
      cell death was observed after 12 and 24 h respectively. Tat peptide neurotoxicity
      could be partially inhibited by blockade of either N-methyl-D-aspartate (NMDA)-
      or non-NMDA receptors, suggesting that excessive neuroexcitation by glutamate or
      its analogues may contribute to tat-neurotoxicity. Furthermore, when both these
      glutamate receptor subtypes were blocked simultaneously, an increased degree of
      neuroprotection was observed. Finally, tat peptide toxicity was also reduced by
      blockade of L-type calcium channels. Calcium imaging revealed that intracellular
      calcium increases slowly upon tat application, predominantly due to entry of
      extracellular calcium. These results indicate that cellular calcium entry through
      voltage-gated calcium channels following activation of both NMDA and non-NMDA
      receptors, and subsequent accumulation of intracellular calcium may contribute to
      the neuronal death induced by tat protein.

PMID- 8552303
TI  - Evidence for the role of protein kinase C in astrocyte-induced proliferation of
      rat cerebromicrovascular endothelial cells.
AB  - The proliferation of cerebral endothelial cells is a crucial step in neural
      angiogenesis and is a process responsive to changes in the surrounding
      environment. Serum-free medium conditioned by rat cortical astrocytes was found
      to accelerate DNA synthesis, induce transient activation of protein kinase C
      (PKC), and increase the endogenous phosphorylation of the PKC-specific substrate,
      the 85 kDa MARCKS protein, in rat cerebromicrovascular endothelial cells (RCEC).
      The stimulatory factor(s) in astrocyte conditioned media (ACM) were heat- and
      trypsin-sensitive and found to have an apparent molecular weight greater than 10
      kDa. The potent PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA), also
      stimulated RCEC proliferation, whereas the inhibition of PKC by staurosporine
      caused a concomitant loss in ACM-induced PKC translocation, MARCKS protein
      phosphorylation and DNA synthesis. These findings implicate PKC activation as a
      critical early event in cerebral endothelial cell proliferation triggered by
      astrocyte-derived mitogen(s).

PMID- 8552304
TI  - Compartmental organization of calretinin in the rat striatum.
AB  - The present study examined the compartmental distribution of a calcium-binding
      protein, calretinin, in the rat striatum. Calretinin-immunoreactive cells were
      homogeneously scattered throughout the striatum, but calretinin-immunoreactive
      fibers were clustered as patches in the medial, central and ventral caudoputamen
      and in the lateral nucleus accumbens. These patches corresponded to striosomes,
      identified by immunostaining for calbindin-D28 K in adjacent sections. In the
      medial nucleus accumbens, calretinin-immunoreactive fibers showed diffuse
      distribution with occasional islands of calretinin-poor zones. These islands
      contained tightly packed, Nissl-stained cells, which have been previously shown
      to correspond to mu-opiate receptor-rich patches. Calretinin-positive fibers fill
      striosomes/patches in the caudoputamen and in the lateral nucleus accumbens and
      avoid them in the medial nucleus accumbens.

PMID- 8552305
TI  - cGMP-dependent protein kinase inhibitor blocks light-induced phase advances of
      circadian rhythms in vivo.
AB  - The suprachiasmatic nucleus (SCN) contains the primary mammalian circadian clock.
      Light synchronizes these circadian rhythms through a mechanism involving the
      release of excitatory amino acids (EAA) and synthesis of nitric oxide (NO) in the
      SCN. In the current study, we investigated whether cGMP-mediated activation of
      cGMP-dependent protein kinase (PKG) is associated with light-induced phase shifts
      of the circadian oscillator. Local administration of the specific PKG inhibitor,
      KT-5823, significantly attenuated light-induced advances in the phase of activity
      rhythms when administered during late subjective night (CT 19). Similar treatment
      at CT 14 had no significant effect on light-induced phase delays. These results
      are the first to implicate PKG in the biochemical pathway(s) responsible for
      photic phase advances, and suggest a divergence in biochemical pathways involved
      in photic phase shifts.

PMID- 8552306
TI  - Differences of somatostatin mRNA in the rat suprachiasmatic nucleus under light
      dark and constant dark conditions: an analysis by in situ hybridization.
AB  - Daily profiles of somatostatin mRNA expression were investigated in the rat
      suprachiasmatic nucleus (SCN) by semiquantitative in situ hybridization
      histochemistry. Under 12 h light/12 h dark conditions, somatostatin mRNA signals
      were higher during the day time (Zeitgeber time (ZT) 1) than during the night
      time (ZT 16). This day-night difference was still maintained in constant darkness
      where the somatostatin mRNA was higher in the subjective day (circadian time (CT)
      1) than in the subjective night (CT 16). Together with previous Northern blot
      hybridization studies, the present observation suggests that the level of
      somatostatin mRNA in SCN neurons is controlled by the circadian clock,
      independent of photic environment.

PMID- 8552307
TI  - Central administration of saikosaponin-d increases corticotropin-releasing factor
      mRNA levels in the rat hypothalamus.
AB  - Saiko agents, Chinese herbal drugs, stimulate corticotropin-releasing factor
      (CRF) release from the hypothalamus, adrenocorticotropin (ACTH) secretion and
      proopiomelanocortin (the precursor for ACTH) gene expression in the anterior
      pituitary. In the present study, the effect of intracerebroventricular injection
      of saikosaponin (SS)-a and -d, two of the main components of saiko agents, on
      hypothalamic CRF gene expression was examined in pentobarbital-anesthetized rats.
      Administration of SS-d, 0.2-2.0 micrograms/kg body wt, increased plasma ACTH
      levels, proopiomelanocortin mRNA levels in the anterior pituitary and the CRF
      mRNA level in the hypothalamus in a dose-dependent manner, whereas SS-a failed to
      have an affect on these levels. These findings indicate that SS-d stimulates both
      CRF gene expression and CRF release, which in turn increases ACTH release and
      proopiomelanocortin gene expression in the anterior pituitary. Therefore, SS-d is
      believed to have an important role both in saiko agent-induced CRF release and
      CRF gene expression in the hypothalamus.

PMID- 8552308
TI  - Enhanced hippocampal theta EEG during whole body rotations in awake restrained
      rats.
AB  - Hippocampal slow wave activity in the theta band was studied in awake restrained
      rats as they were rotated in the horizontal plane both in light and in darkness.
      Monopolar recordings were made with an insulated silver wire (200 microns
      diameter) implanted in the dentate gyrus with reference to the occipital bone.
      Fast Fourier transforms were made of data recorded when the rat was either
      rotated passively or remained immobile. The power in the 6-9 Hz frequency band
      ('type I' theta) was significantly increased during rotations. The same results
      were obtained in experiments performed in the light or in complete darkness.
      These results provide evidence for a role of inertial (possibly, vestibular)
      information in hippocampal spatial representations.

PMID- 8552309
TI  - Apoptosis of neurons in the vestibular nuclei of adult mice results from
      prolonged change in the external environment.
AB  - Pharmacological manipulations which result in abnormal levels of excitatory amino
      acid (EAA) mediated neurotransmission can result in neuronal apoptosis. We
      accordingly hypothesised that manipulations of the external environment which
      induce prolonged EAA-mediated transmission in sensory neurons may also induce
      apoptosis. This hypothesis was tested by placing groups of adult mice, housed in
      their home cage, on a turntable which slowly rotated (0.8 rev./min). This non
      invasive manipulation will have resulted in abnormal discharge patterns in the
      vestibular nuclei. Significantly greater levels of neuronal apoptosis were seen
      in the vestibular complex after rotation for 48 h compared with non-rotated
      controls. This finding was also predicted independently from a computational
      approach.

PMID- 8552310
TI  - Expression of the exon 1A-containing PMP22 transcript is altered in the trembler
      mouse.
AB  - The trembler mouse suffers from a dominantly inherited mutation of the peripheral
      myelin protein 22 (PMP22) gene which results in an abnormal myelination of its
      peripheral nervous system. The recent identification of two different PMP22 mRNA
      differing in their 5' non-translated region led us to monitor their respective
      levels of expression in the trembler peripheral nervous system (PNS) during the
      myelination period. We showed that the steady-state levels of the exon 1A
      containing transcript, which is thought to be involved in the myelination
      process, were greatly reduced in heterozygous and homozygous trembler mice when
      compared to the normal animals. Such a difference was not observed for the exon
      1B-containing transcript. Therefore, our results support the idea that the two
      alternatively used promoters of the PMP22 gene are under different regulation
      control, and that the up-regulation of the exon 1A-transcript is necessary for
      the normal myelination of the mouse PNS.

PMID- 8552311
TI  - Impaired release of cholecystokinin (CCK) from synaptosomes in old rats.
AB  - Cholecystokinin (CCK) is an abundant neurotransmitter peptide in the brain. CCK
      release from synaptosomes obtained from the cerebral cortex, the level of CCK
      mRNA and the tissue concentration of CCK were examined in young and old rats. CCK
      release stimulated by KCl was attenuated in old rats but that stimulated by
      calcium ionophore was comparable in animals at both ages. The CCK mRNA level in
      the cerebral cortex was decreased significantly in old rats despite the
      significant increase in CCK content. These results suggested that aging impaired
      CCK release, resulting in tissue accumulation and a decrease in the synthesis of
      CCK (the level of CCK mRNA).

PMID- 8552312
TI  - Differential expression of glial fibrillary acidic protein (GFAP) in the retinae
      and visual cortices of rats with experimental renal hypertension.
AB  - To examine the expression of the GFAP protein in the retina and visual cortex
      under normal and pathological conditions, hypertension was induced in adult male
      Sprague-Dawley rats by applying silver clips onto renal arteries and the change
      in GFAP expression was followed by Western blotting and immunocytochemical
      staining. One week after operation when the induced hypertension was at the
      initial stage, GFAP expression in the retina was reduced to half of the sham
      control. By 4 weeks, when consistent hypertension was developed, a further
      decrease in the level of GFAP expression in the retina to one third of the sham
      control was observed. Immunocytochemical staining showed that the number of GFAP
      positive cells in the nerve fiber layer of the retina of the hypertensive rat was
      reduced to less than one third of the sham control. However, similar changes in
      GFAP expression in the visual cortex of hypertensive rats were not observed. This
      study represents the first report to date on GFAP expression in the retina and
      visual cortex and includes discussion of the possible mechanisms through which
      GFAP expression is mediated.

PMID- 8552313
TI  - Non-dominant dorsal-prefrontal activation during chess problem solution evidenced
      by single photon emission computerized tomography (SPECT).
AB  - Expert chess players can recall meaningful chess positions with extraordinary
      precision in comparison with inexperienced players. We hypothesized, therefore,
      that their mental performance during chess deliberation could be an appropriate
      target for single photon emission computerized tomography (SPECT) studies. We
      studied cerebral activation with 1110 MBq 99mTc-Bicisate SPECT in five expert
      male chess players during mental solution of a complex chess problem. Region of
      interest (ROI) analysis, in comparison with average weighted cerebellar counts,
      showed activation by 10% or more, of the non dominant prefrontal area (right in
      four dominant right handed players, left in one dominant left handed player) and
      by 2-6% in the non-dominant middle temporal areas. Maximum variability of ROI
      analysis versus cerebellar counts in test/retest evaluation is in our laboratory,
      as in others, 1.5%. Our results are in agreement with neuropsychological studies
      suggesting that the non-dominant hemisphere is specialized for chess skill, and
      show that non-dominant prefrontal and temporal lobe activation during chess
      deliberation can be detected by SPECT.

PMID- 8552314
TI  - Tenascin is present in human muscle spindles and neuromuscular junctions.
AB  - We used immunocytochemistry to investigate the presence of tenascin, an
      extracellular matrix glycoprotein with very restricted tissue distribution, in
      human skeletal muscle. Tenascin was found in a short segment of the muscle
      spindle fibres, in the equatorial region where the sensory endings are found, and
      in the outer layers of the spindle capsule. Tenascin was also found in the
      neuromuscular junctions of the extrafusal fibres. The close spatial relationship
      between tenascin and both sensory and motor nerve endings shown here suggests
      that this glycoprotein is of functional importance in adult nerve-muscle contacts
      in human skeletal muscle.

PMID- 8552315
TI  - Regulatory mechanism of calcium efflux from cultured bovine adrenal chromaffin
      cells induced by extracellular ATP.
AB  - The effect of adenosine-5'-triphosphate (ATP) on Ca2+ efflux from cultured bovine
      adrenal chromaffin cells was examined. ATP stimulated the efflux of 45Ca2+ from
      the cells in a concentration-dependent manner (0.01-1 mM). The 45Ca2+ efflux from
      the cells was also stimulated by adenosine-5'-O-(3-thiotriphosphate) (ATP-gamma
      s), alpha beta-methylene-ATP and adenosine-5'-diphosphate (ADP), but was not by
      adenosine-5'-monophosphate (AMP) and adenosine. The ATP-stimulated 45Ca2+ efflux
      was not affected by deprivation of the extracellular Ca2+ and Mg2+, but was
      dependent on the extracellular Na+ concentrations. ATP increased the influx of
      22Na+ into the cells. These results indicate that ATP stimulates extracellular
      Na(+)-dependent 45Ca2+ efflux from cultured bovine adrenal chromaffin cells,
      probably through its stimulatory effect on membrane Na+/Ca2+ exchange.

PMID- 8552316
TI  - Caprylic acid, a medium chain saturated fatty acid, inhibits the sodium inward
      current in neuroglioma (NG108-15) cells.
AB  - The effects of caprylic acid (CA) on ionic currents were investigated, using the
      whole-cell patch-clamp technique, in differentiated neuroglioma cells. External
      application of CA reduced the peak amplitude of the inward Na+ current, while
      outward currents were not affected. CA (1 and 5 mM) reversibly attenuated the
      peak of the inward Na+ current by 21% (n = 26) and 46% (n = 31), respectively.
      The inactivation curve in the presence of CA was shifted by 8 mV toward
      hyperpolarized potentials, with half-inactivation voltage being -47.9 and -55.9
      before and after external application of CA (5 mM), respectively. This shift was
      readily reversed after 5 min wash. The slope remained unchanged (-8.4 and -8.8
      mV, respectively, n = 4). The activation process was unaffected (CA 5 mM, n = 8).
      Under current-clamp conditions, CA 5 mM (but not 1 mM) reversibly reduced the
      amplitude, and the slope of the rising phase of the action potential. These
      results agree with the fact that free fatty acids can modulate the activity of
      ion channels by mechanisms which do not involve enzymatic or membrane disruptive
      pathways.

PMID- 8552317
TI  - Detection of apoptosis in murine scrapie.
AB  - In order to determine whether apoptosis contributes to the neuronal loss in
      scrapie, in situ end labeling was applied on brains of mice showing clinical
      signs of the disease. Positively labeled, apoptotic neurons were observed in the
      cerebellum, cerebral cortex and hippocampus, areas known to show characteristic
      scrapie-related vacuolation, and were absent in the brains of control mice. We
      conclude that apoptosis plays a role in the neuronal loss that occurs in scrapie.
      The importance of apoptosis as a predominant cell death mechanism in scrapie,
      however, remains to be determined.

PMID- 8552318
TI  - Effects of the pyrethroid insecticide, deltamethrin, on respiratory modulated
      hypoglossal motoneurons in a brain stem slice from newborn mice.
AB  - We have studied the action of deltamethrin on respiratory modulated hypoglossal
      motoneurons in a brain stem slice from newborn mice. Deltamethrin depolarized the
      hypoglossal motoneurons, increased the background synaptic noise and reduced the
      frequency and amplitude of current elicited action potentials. Deltamethrin
      transiently increased the frequency of the respiratory rhythm. Inspiratory
      potentials in hypoglossal motoneurons were decreased in amplitude and increased
      in duration. In conclusion, deltamethrin perturbs the respiratory output from the
      hypoglossal nucleus through postsynaptic actions on hypoglossal motoneurons and
      by affecting the inspiratory synaptic drive.

PMID- 8552319
TI  - Modulation of N-methyl-D-aspartate receptor activity by oxidative stress
      conditions in chick retinal cells.
AB  - The effect of oxidative stress, induced by ascorbate (1.5 mM)/Fe2+ (7.5 microM),
      on the cellular responses to N-methyl-D-aspartate (NMDA) receptor activation was
      evaluated by measuring the release of [3H]GABA induced by NMDA from cultured
      retina cells. In retina cells submitted to oxidative stress the [3H]GABA release
      evoked by NMDA, in a medium containing physiological concentrations of Mg2+ (1.6
      mM) and K+ (4 mM), was significantly higher than in control cells. The [3H]GABA
      release evoked by NMDA was potentiated by glycine and was abolished by MK-801,
      suggesting that the [3H]GABA release was due to NMDA receptor activation. The
      increased effect of NMDA in peroxidized cells was significantly reduced by TTX,
      suggesting that the higher cellular responses to the activation of NMDA receptors
      are due to a hyperexcitability of retina cells submitted to oxidative stress. No
      significant differences were found between the average resting membrane potential
      of control and peroxidized cells. However, membrane potential is more tightly
      regulated by K(+)-channels sensitive to 4-aminopyridine (100 microM), alpha
      dendrotoxin (100 nM) and gamma-dendrotoxin (100 nM) under oxidative stress.

PMID- 8552320
TI  - Transient postnatal thyroxine treatment leads to an increased number of
      cholinergic neurons in the medial septum and to a higher density of cholinergic
      fibers in hippocampal CA3 in rats.
AB  - Newborn male pups of Sprague-Dawley rats received daily injections of buffered L
      thyroxine or saline during the first 12 days postnatally. At the age of 12 weeks,
      the number of immunocytochemically labeled cholinergic neuronal profiles in the
      medial septum/diagonal band (MS/vDB) was counted, and the density of
      acetylcholinesterase (AChE)-positive fibers in four hippocampal subregions was
      measured. Thyroxine-treated rats had more ChAT-positive neuronal profiles in the
      MS/vDB and a higher density of AChE-positive fibers in hippocampal CA3 as
      compared to controls. From this study it is concluded that transient postnatal
      hyperthyroidism leads to an increased cholinergic innervation of hippocampal CA3.

PMID- 8552321
TI  - Glutamate stimulation of arcuate nucleus inhibits responses of subfornical organ
      neurons to plasma hypernatremia and angiotensin II.
AB  - Experiments were done in urethane anesthetized rats to investigate the effect of
      glutamate (Glu) stimulation of arcuate nucleus of the hypothalamus (Arc) on the
      discharge rate of subfornical organ (SFO) neurons during changes in plasma sodium
      concentration and angiotensin II (ANG II) levels. Extracellular recordings were
      made from 67 histologically verified single neurons within SFO. Of these, 17
      (25.4%) were excited by intracarotid infusion of hypertonic NaCl and 21 (31.3%)
      by intracarotid ANG II infusion. Five (29.4%) of the units excited by hypertonic
      NaCl were also excited by Glu stimulation of Arc. Similarly, seven (33.3%) of the
      units excited by ANG II were also excited by Arc stimulation. Additionally, four
      (19.0%) of the units excited by ANG II were inhibited by Glu stimulation of Arc.
      The remaining SFO units did not alter their discharge rate to activation of Arc
      neurons. The response of units to hypertonic NaCl or to ANG II was attenuated
      during simultaneous activation of Arc. These data suggest that Arc may be
      involved in modulating the activity of SFO neurons that function in the detection
      of blood-borne signals from the depletion of intra- and extracellular fluid
      volumes.

PMID- 8552322
TI  - Adenosine activates the potassium channel via a P2 purinoceptor but not via an
      adenosine receptor in cultured rat superior colliculus neurons.
AB  - The effect of adenosine on superior colliculus neurons was examined by whole-cell
      patch clamp recording. Adenosine elicited whole-cell potassium currents. A
      selective A1 or A2a adenosine receptor agonist induced no current and
      furthermore, adenosine-evoked currents were not inhibited by selective A1 or A2a
      adenosine receptor antagonists or a non-selective adenosine receptor (P1
      purinoceptor) antagonist, indicating that the currents are not mediated by
      adenosine receptors. In contrast, P2 purinoceptor agonists, such as 2-methylthio
      ATP (2-MeSATP), ATP, ADP, and AMP, produced similar potassium currents, whereas
      alpha,beta-methylene ATP, beta,gamma-metylene ATP, or UTP had no response. The
      order of their potencies for the current amplitudes was 2-MeSATP > ADP >
      adenosine > ATP >> AMP and this order corresponds to that for the P2Y
      purinoceptor. These results, thus, suggest that adenosine exerts an inhibitory
      effect at the postsynaptic site by activating the potassium channel via a P2Y
      purinoceptor in superior colliculus neurons.

PMID- 8552323
TI  - The effect of N-acetylaspartate on the intracellular free calcium concentration
      in NTera2-neurons.
AB  - We have studied the effect of relatively high concentrations of extracellular N
      acetylaspartate (NAA) on the intracellular free calcium concentration [Ca2+]i in
      NTera2-neurons. While low concentrations of extracellular NAA (0.1, 1 mM) had no
      effect on the [Ca2+]i, high concentrations of extracellular NAA (3, 10 mM)
      elicited sharp and statistically significant elevations of [Ca2+]i. Different
      classes of antagonists of the N-methyl-D-aspartate (NMDA) receptor abolished the
      NAA induced elevations of the [Ca2+]i, indicating the involvement of the NMDA
      receptor in NAA-induced elevations of [Ca2+]i.

PMID- 8552324
TI  - Regeneration of olfactory sensory neurons and reconnection in the aging hamster
      central nervous system.
AB  - Olfactory neuron recovery and axon growth was studied in 12-24 month old hamsters
      after unilateral olfactory nerve transection. At recovery times ranging from 4 to
      126 days olfactory nerve regeneration and axon reconnection to the olfactory bulb
      were examined by anterograde horseradish peroxidase (HRP) neurohistochemistry and
      electron microscopy. Nerve transection produced immediate retrograde neuron
      degeneration and there was no HRP reaction product in the bulb at 4 days post
      transection. By day 35, centrally growing olfactory axons had reached the bulb.
      Axons formed glomeruli smaller than those in the unoperated control bulb and they
      were not always confined to the glomerular layer of the bulb. Some animals showed
      robust fiber growth with axon fascicles penetrating the different layers of the
      bulb and forming ectopic glomeruli along their path. Second order bulb neurons
      contained wheat germ agglutinin HRP reaction product, indicating that
      transneuronal transport had occurred. Electron microscopy confirmed transneuronal
      transport between olfactory axons and second order bulbar neurons. These results
      show that the capacity for olfactory neuron recovery and reconnection persists in
      the hamster well into old age.

PMID- 8552325
TI  - Fetal mesencephalic grafts decrease the rate of dopamine uptake in the non
      lesioned striatum of unilaterally 6-OHDA lesioned rats: an in vivo voltammetric
      study.
AB  - In the present study the influence of intraventricular fetal mesencephalic grafts
      on the elimination rate of extracellular dopamine (DA) in the non-lesioned
      striatum of previously unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats was
      investigated. The elimination of DA was measured after electrical stimulation of
      the medial forebrain bundle in vivo before and after treatment with the high
      affinity uptake inhibitor GBR 12909 (20 mg/kg i.p.) using fast cyclic voltammetry
      (FCV). Rotational behavior induced by amphetamine (AMPH, 2 mg/kg i.p.) and
      tyrosine hydroxylase (TH) immunohistochemistry were used to prove the functional
      recovery and the ingrowth of the graft, respectively. After grafting, the number
      of rotations was decreased and TH-positive cells and fibers were found in the
      grafted striatum. Voltammetric measurements with the aid of a kinetic model
      revealed a smaller rate constant for the in vivo elimination of extracellular DA
      in the non-lesioned striatum of grafted rats compared to that of non-grafted
      controls. This effect was abolished after treatment with GBR 12909. Our results
      will be discussed in relation to the method used and according to recent
      investigations of the specific [3H]DA uptake into striatal synaptosomes in vitro.
      Based on these data we conclude that grafts, placed to the lesioned striatum,
      reduce the DA uptake rate in the non-lesioned striatum due to the reduction of
      the number of functional DA transporters.

PMID- 8552326
TI  - Inflating an indwelling urinary catheter balloon.

PMID- 8552327
TI  - How to safely handle linen.

PMID- 8552328
TI  - Self-test. Handling pediatric emergencies.

PMID- 8552329
TI  - Antibiotic therapy at home. What your patient needs to know.

PMID- 8552330
TI  - Understanding how aging affects wound healing.

PMID- 8552331
TI  - Sotalol. New weapon against ventricular arrhythmias.

PMID- 8552332
TI  - Helping patients with lung injury.

PMID- 8552333
TI  - 30 minutes with Mary.

PMID- 8552334
TI  - Using life lessons to improve patient teaching.

PMID- 8552335
TI  - Actionstat. Methemoglobinemia.

PMID- 8552336
TI  - Managing heart failure: a blueprint for success.

PMID- 8552337
TI  - Oxygen therapy: giving your patient breathing room.

PMID- 8552338
TI  - Surviving a merger. How not to come apart when two hospitals come together.

PMID- 8552339
TI  - Emma benefited from the kindness of strangers.

PMID- 8552340
TI  - When a patient gives you a present.

PMID- 8552342
TI  - New drugs.

PMID- 8552341
TI  - A (TENS)tion!

PMID- 8552343
TI  - Preventing withdrawal syndrome.

PMID- 8552344
TI  - Five keys to succeeding in a new job.

PMID- 8552345
TI  - A sign of victory.

PMID- 8552346
TI  - Is that HMO federally qualified?
AB  - Most HMOs want to be federally qualified, partly because employers prefer to
      contract with managed care plans meeting federal standards. Federal qualification
      is also the first prerequisite for Medicare contracting. This article provides an
      overview of how an HMO becomes federally qualified.

PMID- 8552347
TI  - Clinical assessment algorithm: subacute care admission decisions.
AB  - When using an algorithm to make subacute care admission decisions, the staff's
      uncertainty concerning required resources to meet the patient's needs as well as
      the anxiety about financial loss are alleviated. A system defining levels of care
      and scope of practice based on the patient's acuity is described.

PMID- 8552348
TI  - Legal issues in long-term care--Part I.
AB  - As nurses move from subacute settings to long-term care, they should understand
      that the standard of care applied to the analysis of malpractice cases may be
      different. The definition of malpractice remains the same, the application of the
      standard is unique to the circumstances and the setting.

PMID- 8552349
TI  - The good news about nursing data systems.
AB  - Advances in the areas of nursing data systems now make it possible to better
      define and describe nursing language. This in turn clarifies what nursing
      contributes to the patient's wellness and to the organization's bottom-line.

PMID- 8552350
TI  - Technology assessment: analytical product research.
AB  - In this series on health technology assessment, not only will technology design,
      scientifically validated therapeutic efficacy and relative cost efficiency be
      evaluated, but also the medical ethical challenges of technology introduction
      will be explored. Ideally, these considerations can form the foundation for a
      technology assessment team's discussions.

PMID- 8552351
TI  - The AONE update. Transitions for the future.
AB  - Many AONE members are working beyond the traditional hospital setting, developing
      care networks that encompass community clinics, schools, homes and long-term care
      facilities. These nurses see opportunity in change and are defining new roles and
      meeting new challenges.

PMID- 8552352
TI  - How nurses perceive medication errors.
AB  - It is widely believed that the number of medication errors reported at each
      hospital represents only the tip of the iceberg. The reported data rarely address
      issues beyond the number of incidents that occur. A study conducted at an urban
      community hospital found that medication errors are under-reported and that
      nurses view medication errors as multiple cause incidents.

PMID- 8552353
TI  - A comprehensive quality management approach.
AB  - Value analysis and shared governance are two management concepts relatively new
      to the health care industry. Operating together, they complement each other and
      can result in a comprehensive "quality management" plan. An example of this model
      in a purchasing decision illustrates the benefits that can result from use of
      this collaborative, multidisciplinary approach.

PMID- 8552354
TI  - Revised orientation program for ambulatory care.
AB  - This article describes the revisions made to an orientation program based on the
      introduction of a new organizational culture, expanded classes and a customized
      focus by means of a preceptor program.

PMID- 8552355
TI  - The unit nurse executive: a changing perspective.
AB  - A study describes the perception of unit nurse managers (head nurses/nurse
      executives) as to what constituted their role functions, activities and
      responsibilities. Four major components were used to clarify this description:
      administration, clinical practice, education and research.

PMID- 8552356
TI  - Actualizing empowerment: a case in point.
AB  - A three-hour "think tank" session and continual revision have led to a creative
      reorganization of admissions procedures that successfully addressed a growing
      problem of "boarders." This has resulted in providing more comprehensive patient
      care, increased satisfaction for both family and caregivers and significant cost
      reductions.

PMID- 8552357
TI  - Moving beyond a project's implementation phase.
AB  - Often, much time is spent planning a project's stages. While essential, this
      emphasis often leaves little energy for the implementation phase. Following three
      detailed stages helps illustrate points, defuse conflict and find common ground.

PMID- 8552358
TI  - Coordinating preoperative outpatient testing.
AB  - A lack of a centralized system was causing high outpatient cancellation rates and
      significant delays. As a result, an Operating Room Tracking Committee created
      scheduling and outpatient coordinator positions to provide a centralized,
      coordinated approach to preoperative outpatient processing.

PMID- 8552359
TI  - Nurse practitioner Medicare reimbursement goes to President.
AB  - After months of negotiations, the budget reconciliation package was passed on
      November 17, 1995. Details of Medicare and Medicaid changes and how these will
      affect nurse practitioners follow.

PMID- 8552360
TI  - Emergency medical services need not resuscitate.
AB  - Florida finds a practical solution for a vexing problem: a new form enables
      terminally ill patients and/or their legal designates to assure that EMTs respect
      their right to refuse resuscitation.

PMID- 8552361
TI  - Success with self-containment.

PMID- 8552362
TI  - Nurses' attitudes and concerns about couplet care.

PMID- 8552363
TI  - Nurses' attitudes about floating.

PMID- 8552364
TI  - What everybody knows...

PMID- 8552365
TI  - Retinal vascular changes during aging in Wistar Kyoto rats. Application of
      corrosion cast and scanning electron microscopy.
AB  - Retinal vasculature changes during aging in normal Wistar Kyoto rats maintained
      to longevity without known diseases were studied by corrosion casts and scanning
      electron microscopy (SEM). Six-month-old rat retina showed regular running and
      arrangement of retinal blood vessels. In 18-month-old rats, a definite
      morphological change was moderate tortuosity of the vessels, especially at the
      posterior pole of the retina. In 24-month-old rats, the retinal arteries and
      veins were very tortuous and narrow, and their calibers were irregular. In some
      animals occlusion of the veins and localized constriction of the arteries and
      veins were evident in the vascular casts. Neither arteriovenous crossing defects
      nor microaneurysms were seen. Retinal capillaries showed marked changes:
      localized narrowing, constriction, bead-like features, caliber irregularity and
      occlusion. The corrosion cast method with SEM can demonstrate the details of the
      capillary networks in the rat retina. The findings demonstrated appear to be
      related to aging.

PMID- 8552366
TI  - A rapid method for isolation of retinal pigment epithelial cells from rat
      eyeballs.
AB  - A new, simple method for isolating retinal pigment epithelial (RPE) cells from
      rat eyeballs was developed: incubation of the eyeballs in 0.1% proteinase K
      solution. This method yielded an average of 4 x 10(4) viable RPE cells from each
      Sprague-Dawley rat eyeball in 1 h. These RPE cells were hexagonal and had
      cytokeratin in their cytoplasm and numerous microvilli on their surface, similar
      to RPE cells evaluated in vivo. The results of this study thus show that our
      method for incubating eyeballs in proteinase K can provide good-quality RPE cells
      in sufficient quantities for study in a short time.

PMID- 8552367
TI  - Structure and regional water content of bovine, porcine, and human lenses
      examined with proton nuclear magnetic resonance imaging.
AB  - A proton nuclear magnetic resonance instrument with a 7-tesla field was used for
      nuclear magnetic resonance imaging (NMRI) to study bovine, porcine, and human
      lenses. The NMRI images show detailed changes in the water for normal and
      diseased tissues. The alterations in the nucleus and the cortex in relation to
      the health of the tissue are clearly illustrated.

PMID- 8552368
TI  - Distribution of membrane phospholipids in the rabbit uvea.
AB  - BACKGROUND AND AIMS: Since the uveal tract becomes involved in inflammatory
      disorders, which are known to affect lipid metabolism, we studied normal membrane
      phospholipids (PLs) in order to (1) determine baseline PL profiles of the iris,
      ciliary body, and choroid, and (2) compare and contrast PL profiles of the uveal
      tissues. METHODS: Iris, ciliary body and choroid tissues were isolated from
      rabbit eyes (n = 30) and extracted with chloroform-methanol using a modified
      Folch procedure. Quantitative tissue PL profiles were obtained using 31P nuclear
      magnetic resonance. RESULTS: Fourteen PLs were detected and quantitated in all
      three uveal tissues among which was one unidentified PL at -0.17 ppm. The five
      major PLs in the iris, ciliary body and choroid, respectively, have the following
      PL composition (mole percent of total phosphorus): ethanolamine plasmalogen
      14.58, 15.07, 16.52; phosphatidylethanolamine 13.10, 12.40, 9.23;
      phosphatidylserine 11.24, 10.27, 12.13; sphingomyelin (SM) 11.10, 11.97, 18.21;
      and phosphatidylcholine (PC) 36.61, 36.70, 29.88. Additionally, lysophosphatidic
      acid, phosphatidic acid, lysophosphatidylcholine, phosphatidylinositol, and PC
      plasmalogen or alkacyl PC were detected in all tissues.
      Sphingosylphosphorylcholine also was detected in the ciliary body and choroid.
      Lysophosphatidylethanolamine was detected in the choroid. In addition, 42 PL
      metabolic indexes were calculated from these data, which permitted pathway
      specific lipid analyses. CONCLUSION: This study establishes baseline PL profiles
      of the uveal tract tissues and will permit comparisons with tissues from eyes
      with inflammatory disorders. The PL concentrations in conjunction with the
      indexes demonstrate that overall the choroid has membranes that are less
      permeable to ion translocation than either the iris or the ciliary body, although
      there are compensatory concentration changes between the SM and PC components
      among these three tissues.

PMID- 8552369
TI  - Ultrastructural studies on the corneal superficial epithelium of rats by in vivo
      cryofixation with freeze substitution.
AB  - The method of in vivo cryofixation with freeze substitution (VC-FS) was used to
      examine the natural ultrastructure of the corneal superficial epithelium under
      the transmission electron microscope, and the results have been compared with the
      conventional method. With the VC-FS method, the ultrastructure down to 8 microns
      in depth was well preserved in the specimen. There was a layer of homogeneous
      material thought to be tear film on the corneal surface. Except for the
      intercellular spaces presenting under the first and sometimes also the second
      layers of the epithelial cells, other adjacent cells were in close contact
      without any spaces between them or between the desmosomes. In contrast, when
      using the conventional method, intercellular spaces were found between adjacent
      cells in all the layers of epithelium, and no tear film remained on the corneal
      surface. VC-FS is considered to be a better way to preserve the structure of
      tissue in its natural state than the conventional method and to be a useful
      method for the morphological study of the corneal epithelium and the tear film.
      Intercellular spaces, a kind of artifact, can be reduced by this method.

PMID- 8552370
TI  - Evidence of constriction of optic nerve axons at the lamina cribrosa in the
      normotensive eye in humans and other mammals.
AB  - The ultrastructure of optic nerve axons was examined in several mammals (human,
      cat, rat, sheep, ox, pig, guinea pig, rabbit). Human material was obtained from
      normotensive, glaucoma-free eyes and from eyes with a history of glaucoma and
      raised intra-ocular pressure (IOP). We describe accumulations of organelles
      (principally mitochondria) in optic nerve axons where they traverse the lamina
      cribrosa. Accumulations were most prominent in unmyelinated lengths of axons
      close to lamellae of the lamina cribrosa. Comparable accumulations were not
      apparent in axons in the retina or optic nerve, suggesting that axoplasmic flow
      is constricted at the lamina cribrosa. Accumulations were observed both centrally
      and peripherally to the lamellae, suggesting that flow is constricted in both
      ortho- and anterograde directions. Accumulations of organelles were more marked
      in unmyelinated axons than in adjacent, myelinated axons. In the rabbit, in which
      most axons are myelinated as they traverse the optic nerve head, organelle
      accumulations were observed only in a sparse population of unmyelinated axons. In
      human eyes with a history of raised IOP and glaucoma, the accumulations were
      abnormally large and frequent and in many axons showed dense-body and fibrillar
      changes not seen in normotensive eyes. It is suggested that chronic, partial
      constriction of axoplasmic flow is present at the lamina cribrosa of normotensive
      eyes in a wide range of mammals, including humans, that the constriction results
      from the pressure gradient across the lamina cribrosa and that the constriction
      may be a factor in the many cases of primary glaucoma in which IOP is not raised.

PMID- 8552371
TI  - Detection of varicella-zoster virus genome having a PstI site in the ocular
      sample from a patient with acute retinal necrosis.
AB  - We detected the virus genome in ocular samples from a 65-year-old woman with
      clinically diagnosed acute retinal necrosis using DNA amplification. She
      exhibited occlusive retinal vasculitis, confluent necrotizing retinitis, mainly
      peripheral, and iridocyclitis. For DNA amplification, we used recently published
      primers specific for varicella-zoster virus (VZV) and herpes simplex virus. Using
      VZV primers, we detected the VZV genome in the aqueous humor, but not in the
      vitreous, by amplifying a DNA fragment 642 base pairs in length. HSV DNA was not
      detected. After detecting the VZV genome, PstI restriction endonuclease was used
      because an epidemiological study found that about 25% of the VZV strains in Japan
      carry a mutation lacking a PstI recognition site. The VZV genome from the patient
      had a PstI cleavage pattern, while the positive control had a VZV genome that
      carried a PstI-site-less mutation. We considered our patient with acute retinal
      necrosis to be infected with VZV having a PstI site.

PMID- 8552372
TI  - [The Austrian Nursing Society keeps fighting for schooling].

PMID- 8552373
TI  - [Problems with addiction in the work place].

PMID- 8552374
TI  - [The day clinic as a bridge to the outside].

PMID- 8552375
TI  - [Anorexia nervosa--working with patients with eating disorders].

PMID- 8552376
TI  - [Importance of family cooperation in psychiatric nursing].

PMID- 8552377
TI  - [Hospital financing according to performance. Effect of a diagnosis-related
      accounting system on nursing in the U.S.A].

PMID- 8552378
TI  - Transducers of life and death: TNF receptor superfamily and associated proteins.
AB  - Signal transduction pathways which are initiated by members of the TNF
      superfamily utilize receptors which are devoid of intrinsic catalytic activity.
      Isolation and characterization of death domain (TNF-RI, Fas, TRADD, FADD/MORT-1,
      RIP) and TRAF domain-containing proteins (TRAF-1, TRAF-2, TRAF-3) have partially
      bridged a large molecular gap within one of several signaling pathways which
      originate at the plasma membrane and terminate in the nucleus. The ability of
      these two protein families to selectively dimerize and bind to related receptors
      allows them to govern diverse cellular responses which culminate in cellular
      proliferation, differentiation, effector functions, and apoptosis.

PMID- 8552379
TI  - Adenovirus-mediated p16/CDKN2 gene transfer induces growth arrest and modifies
      the transformed phenotype of glioma cells.
AB  - The p16 (MTS1/CDKN2) gene localized at the 9p21 chromosomal region encodes for a
      cell cycle inhibitor protein and is altered in many human cancers. The frequency
      of p16 alterations in gliomas exceeds 50%. To restore the missing wild-type p16
      gene efficiently in glioma cells an adenovirus vector carrying the full length
      coding sequence of the wild-type p16 cDNA, Ad5RSV-p16, was constructed. Three
      human glioma cell lines, U251 MG, U-87 MG and D54 MG, that did not express
      endogenous p16/CDKN2 gene and were easily infected with adenovirus vectors were
      selected for these experiments. Introduction of the Ad5RSV-p16 in these malignant
      glioma cell lines directed the biosynthesis of functional p16 protein in the
      majority of the exposed cells, significantly inhibited cell growth, influenced
      cell morphology and modified the transformed phenotype of cells including the
      ability to form colonies in soft agar. Flow cytometric studies revealed that the
      majority of the Ad5RSV-p16 infected glioma cells were arrested in the G0-G1
      phases of the cell cycle. These results suggest that p16/CDKN2 inactivation is a
      significant factor in the genesis and progression of gliomas and that the
      restoration of the wild-type p16 protein could have clinical and therapeutic
      utility.

PMID- 8552380
TI  - Interaction of ETS-1 and ERGB/FLI-1 proteins with DNA is modulated by spacing
      between multiple binding sites as well as phosphorylation.
AB  - ETS is a family of transcription factors that contain a highly conserved ETS DNA
      binding domain. Various members of the ETS family are expressed in cells of
      hematopoietic lineage. ETS-1, ETS-2 and ERGB/FLI-1 are expressed at high levels
      in T-lymphocytes. HIV-1 infects T-cells and it has been shown that its LTR
      contains binding sites for various transcription factors. In this study we show
      that the HIV-1 core enhancer is directly regulated by ERGB/FLI-1 protein
      positively, as well as, negatively, depending upon the presence or absence of
      accessory factors in different cell types. In addition, we show that the ETS-1
      transactivation activity is enhanced upon dephosphorylation of the Calmodulin
      dependent Protein Kinase II phosphorylation site located in exon VII. Finally, we
      demonstrate that the spacing between the two EBS cores in palindromic or direct
      repeat sites play a crucial role in binding of ETS proteins to DNA.

PMID- 8552381
TI  - Thyroid pathologies in transgenic mice expressing a human activated Ras gene
      driven by a thyroglobulin promoter.
AB  - Four transgenic mice carrying the human activated c-Ha-Ras gene, the expression
      of which was driven into the thyroid gland by a bovine thyroglobulin promoter,
      have been produced. The M1 and M2 mice developed papillary thyroid carcinomas and
      the M2 mouse also developed a lung carcinoma, however none of them transmitted
      the transgene. Both the M3 and the M4 mice gave rise to transgenic lines. M3
      progeny mice develop a goitre with morphological aspects of hyperplasia as well
      as a thymus hyperplasia. M4 developed a papillary thyroid carcinoma and a lung
      carcinoma. Lung tumors but not thyroid tumors were observed in M4 adult
      transgenic progeny. In this M4 line, thyroid dysgenesis leading to growth
      retardation and premature death was observed upon serial backcross that enhanced
      the DBA/2J genetic background. The development of thyroid tumors in M1, M2, M4
      transgenic mice demonstrates the oncogenic potential of activated Ras gene in the
      thyroid gland. The M4 line raises interesting questions relative to the
      interference between the Ras-mediated signal transduction pathway and thyroid
      morphogenesis.

PMID- 8552382
TI  - Restoration of alpha v beta 5 integrin expression in neoplastic keratinocytes
      results in increased capacity for terminal differentiation and suppression of
      anchorage-independent growth.
AB  - Loss of expression of specific integrins is a feature of poorly differentiated
      oral squamous cell carcinomas (SCCs) and cell lines derived from them. In order
      to test whether there is a direct link between loss of integrins and abnormal
      keratinocyte growth and differentiation, we 'repaired' an SCC line, H357, by
      transfection of its missing integrin subunit, alpha v. We analysed seven
      independent alpha v-expressing clones and compared them with four empty vector
      controls and with the parental cell line. alpha v was expressed on the cell
      surface as a functional alpha v beta 5 heterodimer. The parental cells expressed
      beta 5 mRNA and introduction of alpha v had no effect on beta 5 mRNA levels nor
      on cell surface levels of any other integrins examined. Introduction of alpha v
      had no consistent effect on the growth rate of cells on tissue culture plastic.
      However, anchorage-independent growth was strongly suppressed and the alpha v
      transfectants showed an increased capacity for terminal differentiation, as
      assayed by expression of involucrin. These results are consistent with the known
      role of integrins in regulating keratinocyte terminal differentiation and suggest
      that integrin loss may be directly responsible for the abnormal behaviour of
      keratinocytes in a subset of oral SCCs.

PMID- 8552383
TI  - Regulation of the cell cycle machinery by oncogenic ras.
AB  - The ras proto-oncogene has been implicated during the formation of tumors in vivo
      as well as the transformation of cell lines in culture. Conditional expression of
      an activated ras mutant in Balb/c-3T3 fibroblasts failed to stimulate S phase
      entry in the absence of plasma-derived progression factors, but did shorten the
      G1 interval from 12 to 6 h and abrogate the normal proliferative requirement for
      platelet-derived growth factor. Ras-dependent alteration of the 3T3 cell cycle
      was accompanied by a dramatic increase in the expression of the G1 regulatory
      protein, cyclin D1, while expression of cyclin E and cyclin A proteins were only
      weakly induced. Cyclin/cdk complexes assembled in response to ectopic ras
      expression in the absence of growth factor stimulation bound the cdk inhibitory
      factor, Kip1, and were inactive. However, plasma-stimulated regulatory pathways
      functioned co-operatively with the oncogenic ras molecule to decrease Kip1
      levels, induce the kinase activities associated with cyclins D, E and A, and
      trigger the initiation of DNA replication. Our results suggest that a ras
      activated signal transduction pathway may link environmental mitogenic stimuli to
      the cell cycle machinery via modulation of G1 cyclin expression.

PMID- 8552384
TI  - Isolation and cloning of JTAP-1: a cathepsin like gene upregulated in response to
      V-Jun induced cell transformation.
AB  - The oncogenic potential of Jun in chicken embryo fibroblasts (CEF) varies
      depending on its structure. V-Jun, which has a number of structural differences
      from c-Jun is highly transforming and tumorigenic. C-Jun however, is only weakly
      transforming and is not tumorigenic. We have used this difference in oncogenic
      potential between v-Jun and c-Jun to screen for downstream target genes
      associated with the v-Jun induced transformed phenotype. We describe here the
      identification, cloning and characterization of one of these genes, JTAP-1. JTAP
      1 is consistently overexpressed 7 to 10-fold in CEF transformed by v-Jun compared
      with c-Jun overexpressing or normal CEF. This pattern of expression suggests that
      JTAP-1 is associated with the transformed phenotype. DNA and amino acid homology
      search analysis revealed that JTAP-1 shares a high degree of similarity with over
      100 cysteine proteases from a variety of species and is likely the chicken
      homolog of cathepsin O. Analysis of expression of JTAP-1 in CEF overexpressing
      other oncogenes including v-Ha-ras, v-Src, c-Fos, and Myc revealed that it's
      overexpression is unique to v-Jun transformed cells. Thus, JTAP-1 is likely a
      specific target of v-Jun overexpression and not simply a consequence of cell
      transformation.

PMID- 8552385
TI  - The first exon of Ad12 E1A excluding the transactivation domain mediates
      differential binding of COUP-TF and NF-kappa B to the MHC class I enhancer in
      transformed cells.
AB  - The major histocompatibility complex class I enhancer is the target for
      adenovirus-12 E1A-mediated down-regulation of class I transcription. In Ad12
      transformed rodent cells, the class I enhancer is down-regulated through
      increased binding of the repressor COUP-TF to the R2 element and decreased
      binding of the activator NF-kappa B (p50/p65) to the R1 element. The reduced
      surface levels of class I antigens contribute to the tumorigenic potential of
      Ad12 transformed cells by favoring their immunoescape from cytotoxic T
      lymphocytes. Previous studies using transformed cells containing hybrid Ad5/Ad12
      E1A (plus Ad12 E1B) genes have indicated that sequences within the first exon of
      the 266R Ad12 E1A gene are required for class I down-regulation and
      tumorigenesis. In this study we demonstrate that these same sequences, which
      exclude the Ad12 CR3 transactivation domain, are also required for increased COUP
      TF binding to the R2 element and decreased NF-kappa B binding to the R1 element
      of the class I enhancer. We further show that diminished NF-kappa B binding is
      not due to a lack of NF-kappa B1-p50 in the nuclei of Ad12 transformed rat cells.

PMID- 8552386
TI  - Evidence for the involvement of the Wnt 2 gene in human colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most frequent cancers in humans. It
      develops via a multistage process involving alterations of both protooncogenes
      and tumor suppressor genes. In the present report we determined the level of
      expression of several Wnt genes in CRC by RT-PCR and direct sequencing. While Wnt
      1 was not detectably expressed in any colonic tissues, Wnt-5a gene was
      efficiently expressed both in nontumorous as well as in colonic tumor tissues. In
      contrast, the Wnt-2 gene, which was expressed at low levels in normal colon,
      exhibited overexpression in all tumor tissue samples at the different Dukes'
      stages of CRC progression, including premalignant polyps and liver metastases.
      Overexpression of the Wnt-2 gene occurred also in other digestive neoplasms such
      as gastric and esophageal carcinomas, as well as in diverticulitis associated
      with stenosis or pseudo-tumor.

PMID- 8552387
TI  - The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22)
      chromosome translocation, encodes a constitutive transcriptional activator.
AB  - Molecular characterization of malignant melanoma of soft parts or soft tissue
      clear cell sarcoma which shares t(12;22) chromosome translocation revealed fusion
      of EWS with a transcriptional factor gene ATF-1. The EWS gene, which encodes an
      RNA binding protein, was also shown to be involved in Ewing sarcoma, related
      primitive neuroectodermal tumors and desmoplastic small round cell tumors. In
      order to understand the functional role of EWS-ATF-1 chimeric protein in human
      solid tumors, we have cloned the aberrant human ATF-1 (EWS-ATF-1) cDNA and
      studied its DNA binding, transcriptional activation properties and compared with
      normal ATF-1 protein. Our results demonstrate that EWS-ATF-1 binds weakly to DNA
      in vitro but functions as an efficient constitutive transcriptional activator
      unlike the normal ATF-1 which needs to be induced with cAMP. Deletion analysis
      revealed that EWS-fusion domain functions as a regulatory domain for the
      transcriptional activation properties of EWS-ATF-1 chimeric protein. Deletion of
      leucine zipper domain results in a loss of transcriptional activation of EWS-ATF
      1 chimeric protein suggesting that protein-protein interaction play a role in the
      transcriptional activation properties of EWS-ATF-1. We demonstrate that EWS
      fusion domain negatively regulates the DNA binding activity of EWS-ATF-1 chimeric
      protein. Therefore replacement of part of the amino-terminal kinase regulatory
      domain of ATF-1 protein with EWS regulatory domain results in an altered DNA
      binding, protein-protein interactions and transcriptional activation properties
      of EWS-ATF-1 causing deregulated gene expression which may be responsible for the
      genesis of t(12;22) chromosome translocation-bearing human solid tumors.
      Targeting the transcriptional cofactors (CBP, etc) by EWS-fusion proteins could
      be one of the mechanisms of activation of EWS-fusion proteins in human neoplasia.

PMID- 8552388
TI  - Overexpression of the Ras-related TC21/R-Ras2 protein may contribute to the
      development of human breast cancers.
AB  - Although experimental studies suggest that aberrant Ras function can promote the
      malignant progression of human breast epithelial cells, the occurrence of mutated
      ras genes in breast tumors is infrequent. One possible explanation for this
      apparent paradox is that aberrant function of the Ras-related protein TC21/R
      Ras2, which causes malignant transformation of NIH 3T3 cells via upregulation of
      the Ras signal transduction pathway, may contribute to breast tumor development
      in the absence of Ras mutations. To address this possibility, we utilized two
      complementary approaches. First, we determined that aberrant TC21 function caused
      transformation of the MCF-10A human breast epithelial cell line. TC21-transformed
      MCF-10A cells exhibited altered cellular morphology associated with a disruption
      of cell-cell adherens junctions, formed colonies in soft agar, and showed
      enhanced motility in vitro. These alterations were similar to, but more dramatic
      than, those observed with oncogenic Ras-transformed MCF-10A cells. Furthermore,
      overexpression of normal TC21, but not Ras, also caused transformation of these
      cells. Second, we observed that TC21 protein expression was greatly elevated in 7
      of 9 breast tumor lines when compared to untransformed MCF-10A cells. Taken
      together, these results support the possibility that overexpression of TC21 may
      contribute to aberrant growth properties of breast carcinoma cells.

PMID- 8552389
TI  - Cyclin D1 and p21/waf1 are both involved in p53 growth suppression.
AB  - Overexpression of the wild type p53 gene in normal and transformed cells induces
      G1 arrest of cellular proliferation. In cell lines carrying the valine 135
      temperature-sensitive p53 mutant gene, restoration of wild type p53 protein
      conformation at the permissive temperature causes an increase in the levels of
      cyclin D1, as well as the cyclin/cdk inhibitor p21/waf1. Accumulation of cyclin
      D1 is the result both of (post)transcriptional and post-translational regulatory
      mechanisms. Ablation of cyclin D1 induction by antisense cDNA microinjection
      significantly delays the onset of growth arrest, indicating that increased cyclin
      D1 levels likely contribute to wild type p53 G1 arrest. Whereas antisense
      ablation of either cyclin D1 or p21/waf1 can delay the onset of p53-induced
      growth arrest, ablation of neither is able to overcome a pre-existing p53-induced
      G1 block. In summary, the accumulated evidence indicate that induction of both
      cyclin D1 and p21/waf1 are involved in establishing the p53-mediated growth
      arrest in murine cell lines expressing temperature sensitive p53 protein.

PMID- 8552390
TI  - Gamma-radiation induces upregulation of Bax protein and apoptosis in
      radiosensitive cells in vivo.
AB  - Lymphoid cells and small intestinal epithelial (SIE) cells are among the most
      radiosensitive in the body. The factors that account for the differential
      sensitivity to gamma-radiation among different tissue-types remain poorly
      understood, but can only partly be explained by differences in rates of cell
      proliferation. Here we demonstrate that exposure of mice to 800 cGy of gamma
      radiation results in rapid elevations in the levels of the Bax protein, a pro
      apoptotic member of the Bcl-2 protein family, in lymphoid cells and SIEs. gamma
      Radiation-induced increase in Bax protein were evident within 2 h and persisted
      for at least 24 h, as determined by immunoblotting and immunohistochemical
      assays. Increases in Bax were followed by massive apoptosis in lymphoid organs
      and in the small intestinal crypts, as determined by morphological criteria and
      in situ end-labeling of fragmented nuclear DNA by terminal deoxynucleotidyl
      transferase (TUNEL method). Radiation did not induce elevations in Bax or
      apoptosis in radioresistant tissues such as heart, skeletal muscle, brain,
      kidney, liver, lung, vascular smooth muscle and connective tissue. The findings
      suggest that Bax may be one of the mediators of radiation-induced apoptosis in
      vivo.

PMID- 8552391
TI  - DNA-binding by oncoprotein E2a-Pbx1 is important for blocking differentiation but
      dispensable for fibroblast transformation.
AB  - The t(1;19) chromosomal translocation of pediatric pre-B cell lymphoblastic
      leukemia produces the E2A-PBX1 oncogene, which can transform fibroblasts, induce
      acute myeloid leukemia and T cell lymphomas in mice, and immortalize factor
      dependent myeloid progenitors in cultured marrow. The homeodomain of Pbx1 binds
      ATCAATCAA, and while Pbx1 does not activate transcription through this motif, E2A
      Pbx1 induces constitutive transactivation. Here, we investigate whether DNA
      binding by Pbx1 or transcriptional activation by E2A are essential for the
      transforming abilities of E2A-Pbx1. Elimination of DNA-binding in E2A-Pbx1 by
      point mutations in the Pbx1 homeodomain or by large deletions that removed the
      Pbx1 homeodomain and carboxyl terminus did not alter ability of E2A-Pbx1 to
      induce focus-formation in fibroblast, even though these mutations completely
      eliminated its ability to activate transcription through the PRS. These same DNA
      binding mutations, however, severely impaired or eliminated the ability of E2A
      Pbx1 to immortalize factor-dependent myeloid progenitors in marrow cultures.
      Elimination of the first transcriptional activation domain of E2A abolished both
      fibroblast and myeloid transforming activities while elimination of the second
      altered neither of these activities. We conclude that DNA-binding is important
      for the ability of E2A-Pbx1 to disrupt differentiation, as evidenced in
      myeloblast immortalization, but dispensable for its ability to induce focus
      formation, and that the aminoterminal domain of E2A, which strongly activates
      transcription, is essential for both transforming activities.

PMID- 8552392
TI  - A cellular protein activates the sequence-specific DNA-binding of p53 by
      interacting with the central conserved region.
AB  - Mutational inactivation of the p53 gene product is one of the most common genetic
      aberations so far identified in human cancers. The p53 protein suppresses the
      transformed phenotype by transactivation or repression of genes involved in cell
      growth control. Missense mutations in the p53 protein coding sequence observed in
      human cancers are clustered within a central conserved (conformational) domain
      spanning amino acid residues 100-300 of a total of 393. Using the conformational
      domain of p53 fused with protein A, we have shown that the p53 conformational
      domain possesses Zn+2-dependent, sequence-specific DNA-binding activity. In
      addition to binding DNA, this domain interacts with at least five cellular
      proteins ranging in sizes from 30K to 90K M(r) and with the SV40 large T antigen
      viral oncoprotein. We investigated these cellular proteins for their modulatory
      effects on the sequence-specific DNA binding activity of full-length wild-type
      p53. A mixture of p53 conformational domain-binding proteins in bulk enhanced the
      DNA-binding activity of p53 greater than two-fold. Selective elution of the p53
      binding proteins from the p53 hybrid protein by using a sequential step-wise NaCl
      gradient implicated one protein of 35K M(r) as contributing to a greater than
      four-fold activation of p53 DNA-binding activity. A p53 conformational domain
      protein containing a tumor-derived mutation at amino acid 175 failed to associate
      with the 35K M(r) protein. We propose that proteins interacting with the
      conformational domain of wild type p53 regulate the DNA-binding activity of p53,
      thus providing a biochemical basis for the alterations in its function induced by
      point mutations.

PMID- 8552393
TI  - Differential cell death in immortalized and non-immortalized cells at confluency.
AB  - Rat embryo fibroblast cells that have been immortalized by viral transfection
      have an altered cell cycle control. These cells have been observed to die via an
      apoptotic death when grown to confluency which, in at least one of the cell line
      pairs studied, was independent of the presence of wildtype or mutant p53. This
      confluency-dependent apoptotic cell death was observed in thirteen of fourteen
      rodent and human cell lines tested. In contrast, primary rodent and human cell
      strains (fibroblasts) entered a quiescent G1/G0 state at confluency. Two weeks
      later, these non-immortalized cells underwent necrosis, not apoptosis. As the
      medium was not replenished during this two week period, cell necrosis was
      probably due to deprivation of nutrients and growth factors. These results
      indicate that mechanisms of cell death may differ between transformed and non
      transformed cells under physiological stressed situations, such as high cell
      density. It may be possible to exploit these differences to increase the efficacy
      of chemotherapeutic compounds towards neoplastic cells.

PMID- 8552394
TI  - Expression of the bZIP transcription factor gene Nrl in the developing nervous
      system.
AB  - Proteins of the Maf/Nrl subfamily of bZIP transcription factors are involved in
      the regulation of tissue-specific gene expression. The Nrl gene, initially
      identified from a subtracted retinal library, is expressed in all cell layers of
      the adult retina, including photoreceptors. The Nrl protein has high sequence
      homology with Maf proteins, binds to an AP-1 like sequence element, and in
      photoreceptors appears to be involved in regulating the expression of rhodopsin.
      In the present study, we investigated the expression of Nrl in the developing and
      adult mouse using in situ hybridization and RT-PCR. We demonstrate that beginning
      at embryonic day 12.5 Nrl is expressed throughout the developing central and
      peripheral nervous system, with the exception of the nasal epithelium. The
      spatial pattern of hybridization suggests that Nrl is transcribed in post
      mitotic, differentiating neurons, the developing cephalic mesenchyme and lens.
      Nrl expression is downregulated postnatally in the brain, and becomes restricted
      to neocortex and brainstem in the adult. High levels of Nrl transcripts, however,
      persist in the mature photoreceptors and other retinal neurons. Our studies
      suggest a role for the Nrl protein in neuronal differentiation and in mature
      neurons of the adult retina.

PMID- 8552395
TI  - Identification of domains required for transcriptional activation and protein
      dimerization in the human papillomavirus type-16 E7 protein.
AB  - To analyse the potential of the E7 oncogene of HPV-16 to activate transcription,
      we constructed hybrid proteins containing various portions of the HPV-16 E7
      protein fused to the DNA binding region of the bacterial LexA repressor. We found
      that full length HPV-16 E7 is capable to mediate activation of two different
      reporter genes, which carry LexA binding sites in their promoters. In contrast,
      E7 from HPV-11, a low-risk type papillomavirus, was unable to activate
      transcription, when analysed in the same assay. Mutations in the transforming
      domains of HPV-16 E7 did not affect the ability of the protein to activate
      transcription, indicating that it represents a novel function of the oncoprotein,
      which is not sensitive to any known inactivating mutations. Analysis of E7
      subdomains revealed that the N-terminal part of HPV-16 E7 retains the capacity to
      activate transcription. A second trans-activation domain is located in the C
      terminal part of E7; however, in the context of the full length E7 protein this
      activity is blocked by an adjacent domain. These results reveal a second pathway
      for transcriptional activation by HPV-16 E7, independent of its interaction with
      pRB-E2F complexes. Using the E7-LexA hybrid proteins, it is shown that E7 can
      form homodimers and this property involves a zinc finger structure in the C
      terminal part of the protein, partially overlapping with the domain that
      negatively regulates transcriptional activation by E7.

PMID- 8552396
TI  - Amplification and expression of EMS-1 (cortactin) in head and neck squamous cell
      carcinoma cell lines.
AB  - Amplification of chromosome 11q13 DNA sequences is detected in approximately 30%
      of primary head and neck squamous cell carcinomas (HNSCC). The amplified region
      includes genes for cyclin D1, hst-1, int-2, and more recently, ems-1. Ems-1
      encodes an 80/85kd cytoskeletal associated protein termed cortactin, which has
      been shown to bind F-actin and is a pp60src substrate. We investigated 16 HNSCC
      cell lines for ems-1 DNA amplification and gene expression by western blotting
      and immunofluorescence using mAb 4F11. Amplification of ems-1 DNA was detected in
      8/16 (50%) cell lines and was related directly to over-expression of cortactin by
      western blotting and immunofluorescence. Western blotting detected both forms of
      cortactin, p80 and p85, at equal intensity. Immunofluorescent staining revealed
      low levels of cortactin localized to the cytoplasm and surface membrane in normal
      bronchial epithelial cells and tumor cell cultures with single copy ems-1 DNA. In
      contrast, tumor cell cultures with ems-1 DNA amplification demonstrated intense,
      homogeneous cortactin cytoplasmic staining. These results suggest that
      overexpression of p80/85 may be a useful marker to identify 11q13 amplification,
      a molecular alteration correlated with the presence of lymph node metastasis in
      head and neck cancer.

PMID- 8552397
TI  - Expression of TrkC in favorable human neuroblastomas.
AB  - Human neuroblastomas have been found to express the neurotrophin receptors TrkA
      and TrkB. Expression of TrkA correlates with favorable outcome, while expression
      of full-length TrkB is associated with unfavorable, more aggressive, N-myc
      amplified tumors. In this study we have determined the expression of TrkC in
      neuroblastoma primary tumors and cell lines. Using probes for the extracellular
      domain and the tyrosine kinase domain of human TrkC, we found by Northern
      analysis that TrkC mRNA is expressed in 14 of 55 (25%) tumors from a
      representative panel of neuroblastomas. A 14 kb transcript was detected by both
      probes, indicating that it would encode the full-length TrkC protein. A
      significant association was found between TrkC mRNA expression detected by
      Northern analysis and lower stage tumors [stage 1, 2, 4S, 11 of 30 (37%); vs
      stage 3, 4, 3 of 25 (12%), chi2 = 4.4, P < 0.04]. Only one of eight primary
      tumors with N-myc amplification had detectable TrkC mRNA expression and none of
      the eight neuroblastoma cell lines expressed TrkC by Northern analysis. Our
      results suggest that TrkC is involved in the biology of favorable neuroblastomas.

PMID- 8552398
TI  - Loss of Rb and Myc activation co-operate to suppress cyclin D1 and contribute to
      transformation.
AB  - Cyclin D1 can bind and phosphorylate the product (pRb) of the retinoblastoma gene
      (RB-1) and recent evidence suggests pRb, in turn, may regulate cyclin D1 protein
      expression. In transformed cell lines, loss of pRb activity strongly correlates
      with a decrease in cyclin D1 protein expression, and conversely, introduction of
      pRb can induce cyclin D1 promoter activity. We show here that pRb does not
      regulate cyclin D1 directly as basal and serum-stimulated levels of cyclin D1
      protein and kinase activity are similar in wildtype and pRb-deficient primary
      mouse embryonic fibroblasts (MEFs). These observations suggest that the
      suppression of cyclin D1 in pRb-minus tumour cell lines requires both loss of pRb
      and at least one additional genetic event. We have determined that constitutive,
      ectopic Myc expression in pRb-deficient, but not wildtype, MEFs suppresses cyclin
      D1 protein expression and kinase activity. Regulation is evident at either the
      level of RNA or protein expression. Phenotypically, pRb-deficient MEFs
      consistently exhibited a delayed growth response in comparison to wildtype MEFs.
      This growth delay is abrogated in pRb-deficient MEFs which are expressing ectopic
      Myc protein, coincident with the loss of cyclin D1 protein expression. Moreover,
      these cells exhibit an increased proliferative capacity, and they no longer show
      contact inhibition. Our results support a cross-regulatory mechanism between Myc,
      pRb and cyclin D1 and suggest a novel role for cyclin D1 in tumorigenesis.

PMID- 8552399
TI  - Transactivation activity of Maf nuclear oncoprotein is modulated by Jun, Fos and
      small Maf proteins.
AB  - The v-maf oncogene encodes a nuclear bZip protein which specifically recognizes
      relatively long palindromic sequences related to an AP-1 site. In this study, we
      investigated the relationship of transactivation and transformation activity of
      Maf. The amino-terminal two thirds of the molecule were dispensable for its DNA
      binding activity but conferred its transactivation potential. Transactivation
      activities of a set of deletion mutants correlated well with their cell
      transforming abilities. However, a point mutant associated with enhanced
      oncogenic activity was not more effective in transactivation than the wild type,
      suggesting that some other function(s) of Maf is also important for its
      transforming ability. We also examined the effect of other bZip proteins on the
      transactivation activity of Maf. Three small Maf family proteins (MafK, MafF and
      MafG), which are missing the transactivation domain of v-Maf, competitively
      inhibited transactivation by Maf. Co-expression of Jun or Fos also affected the
      transactivation potential of Maf by forming Maf/Jun or Maf/Fos heterodimers of
      distinct DNA-binding specificities. In addition to these factors, we noticed the
      presence of a strong endogenous transactivating activity associated with a
      sequence related to an NF-E2 site rather than the typical AP-1 site in fibroblast
      cells. These results indicate that AP-1 site-like cis-regulatory elements of
      eukaryotic genes are regulated by multiple sets of bZip dimers with different DNA
      binding and transactivation properties.

PMID- 8552400
TI  - Mutations of the p16 gene in gliomas.
AB  - In the present study we investigated the frequency of p16 gene exon 2 mutations
      in 35 malignant gliomas, using either direct sequencing of the PCR products or
      cloning into the pCRII vector and sequencing of the cloned PCR products. No
      mutations were detected during direct sequencing of the PCR products. However,
      after sequencing of individual clones, we found multiple mutations in 5 tumors
      involving codons 73(GCC to ACC, Ala to Thr), 76 (GCC to GTC, Ala to Val), 85(GCT
      to ACT, Ala to Thr), 98(CAC to TAC, His to Tyr), 102 (GCG to GTG, Ala to Val),
      106 (GTG to ATG, Val to Met), 107 (CGC to TGC, Arg to Cys), 127 (GCA to GTA, Ala
      to Val), 128 (CGG to TGG, Arg to Trp) and 136 (GGC to GAC, Gly to Asp). Mutations
      were found only in glioblastomas and were either C to T or G to A transitions.
      Each mutation was detected in a small percentage of tumor cells (1.3-22%) using
      individual colony sequencing and southern hybridization with mutant
      oligonucleotides, consistent with the heterogenous cell population of
      glioblastomas. The presence of p16 gene mutations only in glioblastomas suggests
      that they are late events in glioma development.

PMID- 8552401
TI  - Regulation of cyclin and cyclin-dependent kinase gene expression during lens
      differentiation requires the retinoblastoma protein.
AB  - The retinoblastoma protein (pRb) functions as a negative regulator of the cell
      cycle and is essential to maintain certain cell types in a post-mitotic state
      during terminal differentiation. In the ocular lens, inactivation of this protein
      is sufficient to cause lens fiber cells, which are normally post-mitotic, to
      enter the cell cycle. The current studies address whether regulation of the cell
      cycle during lens fiber differentiation in normal lenses or in lenses in which
      pRB has been inactivated is accompanied by changes in expression of cyclin and
      cyclin-dependent kinase genes. In the normal lens, our experiments using in-situ
      hybridization reveal that the expression of cyclin A, cyclin B1, cdc2 and cdk2 is
      restricted to the proliferative epithelial cells, with no expression in the
      differentiating fiber cells. Cyclins D1 and D2 and cdk4 show a less restrictive
      pattern and are expressed in some of the post-mitotic cells. Lenses from RB
      deficient embryos, in contrast, show inappropriate expression in the fiber cells
      of cyclins A, B1 and E, as well as cdc2 and cdk2. The lens fiber cells in these
      embryos express protein markers for differentiation, such as beta- and gamma
      crystallins, even though the cells do not withdraw from the cell cycle. These
      results indicate that the regulated expression of multiple cell cycle regulatory
      genes during lens fiber cell differentiation requires the presence of pRb.

PMID- 8552402
TI  - Nerve growth factor induces a multimeric TrkA receptor complex in neuronal cells
      that includes Crk, SHC and PLC-gamma 1 but excludes P130CAS.
AB  - Binding of nerve growth factor (NGF) to the TrkA receptor results in
      homodimerization, and activation of the intrinsic tyrosine kinase activity of the
      receptor, leading to multiple phosphorylations. We investigated the in vivo
      formation and composition of the receptor complex induced by NGF in a central
      nervous system-derived cell line (B104-neo), transfected with the human cDNA for
      TrkA. Using receptor-activated immunoprecipitation followed by analysis of the
      immune complexes by SDS-PAGE and immunoblotting, we show that NGF induces the
      association of TrkA with c-Crk-II in a multimeric complex that also includes SHC
      and PLC-gamma 1. While the tyrosine phosphorylation of TrkA, SHC and PLC-gamma 1
      increased with time in the presence of NGF and was inhibited by the tyrosine
      kinase inhibitor K252a, the state of tyrosine phosphorylation of c-Crk-II did not
      appear to change with NGF treatment. Immunodepletion studies demonstrated that
      the interaction of c-Crk-II with TrkA not only occurs indirectly through the SHC
      proteins, but may also involve another mode of binding. Furthermore, we show that
      c-Crk-II is associated with tyrosine phosphorylated p130CAS in unstimulated cells
      and that NGF treatment results in the de-association of p130CAS/c-Crk-II complex
      in the absence of an apparent change in the tyrosine phosphorylation of p130CAS.
      These results clearly implicate c-Crk-II in the NGF signaling pathway and support
      the concept that more than one signaling molecule known to participate in the
      activation of Ras associates with TrkA upon NGF treatment.

PMID- 8552403
TI  - Biochemical and biological consequences of changing the specificity of p21ras
      from guanosine to xanthosine nucleotides.
AB  - The D119N mutation of p21ras was prepared by site-directed mutagenesis. Its
      nucleotide binding properties were investigated using fluorescently labelled
      guanosine and xanthosine nucleotides. Its affinity for guanosine nucleotides is
      severely reduced, with a concomitant increase in the affinity for xanthosine
      nucleotides, which leads to an almost complete reversal of base specificity. The
      protein is a GTPase as well as a XTPase and the hydrolysis reaction can be
      efficiently stimulated by GAP. Dissociation of XDP from the mutant is stimulated
      by the guanine nucleotide exchange factor Cdc25Mm in a similar manner to that of
      GDP from wildtype. The interaction of the mutant with the effector domain of c
      Raf kinase or Ral-GEF is normal. In microinjection experiments in PC12 and NIH3T3
      cells the protein behaves as an oncogenic mutant due to its high dissociation
      rate for GDP. However, when the protein is loaded with XDP before microinjection
      the onset of the oncogenic signal can be efficiently retarded. Thus, the protein
      behaves initially as wildtype and later as an oncogenic protein.

PMID- 8552404
TI  - Allelic deletion mapping on chromosome 5 in human carcinomas.
AB  - We analysed allelic deletions on chromosome 5 in microdissected human non-small
      cell lung cancers. Thirty-four primary squamous cell carcinomas, 15 primary
      adenocarcinomas and five regional lymph node metastases were investigated for
      loss of heterozygosity (LOH) in chromosomal region 5p15-q21. The sites analysed
      included the APC tumor suppressor gene at 5q21, five polymorphic microsatellite
      markers and the putative tumor suppressor locus del-27, that was assigned to
      chromosomal region 5p13-12 by fluorescence in situ hybridization (FISH) analysis.
      Allelic deletions encompassed larger genomic regions more often in squamous cell
      carcinomas than in adenocarcinomas. The del-27 amd APC regions were identified as
      two distinct regions with the highest LOH frequencies within 5p15-q21. In
      squamous cell carcinomas LOH frequencies were 73% at the del-27 and 70% at the
      APC locus. In adenocarcinomas LOH at the del-27 and APC loci occurred in 38% of
      the informative cases. Allelic deletion of the APC gene and at the del-27 locus
      was also detected in the metastases. The results suggest involvement of at least
      two tumor suppressor genes on chromosome 5 in lung tumorigenesis.

PMID- 8552405
TI  - The effects of H2 and non-H2 genes on the survival of Onchocerca lienalis
      microfilariae in the mouse.
AB  - The effect of H2 and non-H2 genes in a mouse model of protective immunity against
      Onchocerca lienalis microfilariae have been investigated. Non-H2 effects were
      determined using CBA, BALB/c, B10, SJL and TO strains. All were permissive for
      establishment of a primary infection with microfilariae, although significant
      differences in parasite recoveries were evident amongst the various strains. The
      effect of H2 genes upon a primary infection was investigated using H2 congenic
      B10 and BALB strains, B10, B10.S, B10.BR, B10.D2/n, BALB/c, BALB.B, and BALB.K.
      Significant H2 effects were seen among the relatively weak responder B10 strains,
      but were not present among the relatively strong responder BALB strains. These
      results support a dominant effect of non-H2 genes following primary exposure to
      microfilariae, and a 'fine tuning' effect of H2 genes that is apparent only in
      weaker responding strains. Upon reinfection of all the strains investigated, a
      gradation of protection was detected that appeared to be exclusively dependent
      upon H2.

PMID- 8552406
TI  - Immunogens containing sequences from antigen Pf332 induce Plasmodium falciparum
      reactive antibodies which inhibit parasite growth but not cytoadherence.
AB  - Immunogens based upon sequences from the P. falciparum asexual blood stage
      antigen Pf332 were assessed for their capacity to induce antibodies inhibiting
      parasite growth or cytoadherence of infected erythrocytes in vitro. Selection of
      the Pf332 sequences was based on their reactivity with the human monoclonal
      antibody (MoAb) 33G2 which inhibits parasite growth as well as cytoadherence in
      vitro. Octameric multiple antigen peptides (MAP) were assembled based upon either
      a trimer of the minimal epitope recognized by the MoAb, VTEEI, or a Pf332
      sequence including that motif, SVTEEIAEEDK. A dimer of SVTEEIAEEDK was also
      expressed in Escherichia coli, genetically fused to ZZ, two IgG-binding domains
      of staphylococcal protein A. Rabbit antibodies elicited by the immunogens reacted
      with Pf332 in immunofluorescence and in ELISA with Pf332 peptides which were also
      recognized by MoAb 33G2. The MAP with branched (VTEEI)3 peptide induced the
      highest titres of P. falciparum-reactive antibodies. In contrast to MoAB 33G2,
      none of the polyclonal Pf332 reactive sera cross-reacted with repeat sequences of
      the malaria antigen Pf155/RESA. The polyclonal Pf332-reactive antibodies
      inhibited parasite growth efficiently but had no or very low inhibitory effect in
      a cytoadherence assay. Thus, while Pf332 may be an important target for parasite
      neutralizing antibodies its involvement in cytoadherence is unclear.

PMID- 8552407
TI  - Heat shock proteins of Toxoplasma gondii.
AB  - We have investigated heat shock protein (HSP) expression in mouse-virulent and 
      avirulent strains of Toxoplasma gondii by performing Western blot analysis using
      a monoclonal antibody against HSP65 of Mycobacterium bovis and a polyclonal
      antiserum against HSP70 of Plasmodium falciparum as primary antibodies. We
      initially observed that murine macrophages express HSP65 when infected with
      either virulent or avirulent strains, a result which contradicts previous
      reports. Differential HSP expression consistent which virulence was observed
      between strains, with high levels of a 70kDa HSP (HSP70) only detected in
      virulent strains in vivo. This protein was not observed in virulent strains in
      the immunocompromised mouse or in vitro, suggesting induction by immunological
      stress. This protein was only poorly expressed in avirulent strains. A 65kDa
      protein was observed in all strains in vivo and in vitro, suggesting a shared
      epitope with HSP70. These results are consistent with the hypothesis that the
      induced expression of HSP70 in virulent strains of T. gondii by immunological
      stresses may provide protection for these strains against cell damage associated
      with invasion of the host, allowing the virulent strains to persist as
      tachyzoites without the requirement for the encystation observed in avirulent
      strains.

PMID- 8552408
TI  - Anti-fecundity immunity induced in pigs vaccinated with recombinant Schistosoma
      japonicum 26kDa glutathione-S-transferase.
AB  - We have recently reported (Liu et al. 1995) that immunization of mice with
      recombinant 26kDa GST (reSjc26GST) induces a pronounced anti-fecundity effect
      after experimental infection with Chinese Schistosoma japonicum. A similar
      vaccination trial was thus carried out on pigs, important reservoirs for
      schistosomiasis japonica, using purified, reSjc26GST and reSjp26GST from
      Schistosoma japonicum with alum as adjuvant; in general, similar results were
      obtained with the two sources of recombinant 26kDa GST. Some protection in terms
      of worm reduction, significant with males, against challenge infection was
      observed in vaccinated pigs. Moreover, prior to challenge, levels of specific
      anti-re26GST antibodies in the vaccinated pigs were significantly higher than in
      non-vaccinated pigs as determined by GST-ELISA. The most striking feature of the
      vaccine trial was the significant reduction in the number of eggs, especially
      mature eggs, in the livers of vaccinated animals. The results indicate that
      immunization with recombinant Sj26GST can provide some reduction in worm burden
      following exposure of pigs to reinfection with S. japonicum. In addition,
      reSj26GST can induce an anti-fecundity effect, thereby reducing pathology,
      coupled with a delay or interruption of the development of immature to mature
      eggs in the liver. As a consequence, vaccination with Sj26GST would also prove
      useful in affecting the transmission of schistosomiasis japonica.

PMID- 8552409
TI  - Vaccination of patas monkeys experimentally infected with Schistosoma haematobium
      using a recombinant glutathione S-transferase cloned from S. mansoni.
AB  - The capacity of a recombinant glutathione S-transferase from Schistosoma mansoni
      (rSm28GST) to vaccinate primates (Erythrocebus patas) against a heterologous
      infection with Schistosoma haematobium has been tested. Two injections of the
      purified molecule with Muramyl-Di-Peptide (MDP) as adjuvant resulted in a high
      level antibody response in the five immunized animals and in a significant
      reduction in worm fecundity compared to the controls which received adjuvant
      alone. Mean levels of daily egg excretion in urine an faeces were reduced by
      respectively 55% and 74% although perfusion revealed that worm burdens were
      similar in both groups. The protective effect was long lasting since it was
      maintained up to the end of the experiment, 42 weeks after infection. Hatching
      rates and the numbers of intra-uterine eggs were also significantly affected by
      the vaccination. Tissue eggs were also drastically diminished in the urogenital
      system (-80%) but the reduction was not statistically significant. One animal was
      not protected by the immunization. There was a good correlation between
      parasitological data and the intensity of bladder lesions assessed by microscopic
      examination. Polypoid formations together with an intense exudation of the lamina
      propria were frequently seen in the controls but rarely in the vaccinated group
      where formation of scar tissue was predominant. These results underline the
      vaccine potential of the recombinant Sm28GST as a possible valuable prophylactic
      tool for the control of egg-induced pathology and transmission of African
      schistosomes.

PMID- 8552410
TI  - Isotype-specific characterization of antibody responses to Onchocerca volvulus in
      putatively immune individuals.
AB  - Isotype/subclass-specific antibody responses to adult Onchocerca volvulus extract
      (OvAg) were assessed by both ELISA and immunoblotting for a group of putatively
      immune individuals (PIs, n = 29) from a hyperendemic area in Ecuador and for a
      group of infected individuals (INFs, n = 470) from the same regions. As a group,
      the PIs have been previously shown to possess lower levels of OvAg specific IgG1,
      IgG2, IgG3 and IgG4 than INF's but semi-quantitative analysis revealed that the
      relative proportions of these subclasses differs between the two groups. The IgG
      of the PI group contained a higher proportion of IgG3 and a lower proportion of
      IgG4 than the INF group. The frequency distribution of IgG3 responses was similar
      for the PI and INF groups. The frequency distributions for IgG1, IgG4 and IgE
      were significantly different between the PI and INF groups. A subgroup of the PIs
      were identified from frequency distributions and multivariate plots of individual
      isotype responses as having antibody responses (mainly IgG4) possibly indicative
      of cryptic infection. High IgE responses were exclusive to INF individuals, and a
      rare response type of high IgG3 with negligible levels of other
      isotypes/subclasses was seen only in the PI group. However, the majority of the
      PIs had negligible responses for all antibody classes. Immunoblots demonstrated
      no obvious differences in qualitative recognition between the PIs and INFs.

PMID- 8552411
TI  - NK and LAK functions in human chronic Chagas disease.
AB  - Natural killer (NK) and lymphokine activated killer (LAK) functions were measured
      in 40 patients with chronic Chagas disease divided into
      asymptomatic/indeterminate (18) and symptomatic forms (22) and in 24 healthy
      controls. A chromium release assay was used employing K562 or P815 cell lines as
      targets. There was no difference in either NK or LAK activity between the three
      groups. A small number of patients in each group showed results above or below
      the normal range for controls. However, there was no correlation between NK and
      LAK values in the same individual. In conclusion, NK immunosuppression associated
      with human chronic Chagas disease.

PMID- 8552412
TI  - Susceptibility to Plasmodium berghei infection in rats is modulated by the acute
      phase response.
AB  - Brown Norway (BN) and Sprague Dawley (SD) rats are known to differ in their
      susceptibility to infection with sporozoites of Plasmodium berghei, as measured
      by the density of liver schizonts. Because of the known inhibitory effect of non
      specific immunomodulators on schizont development, we compared some aspects of
      the acute phase response in these two rat strains. LPS induced IL-6 production
      was measured in supernatants of spleen cells and peritoneal macrophages of both
      strains. SD rats, which are the least susceptible to P. berghei sporozoites,
      showed significantly higher IL-6 production by macrophages from both sources.
      When LPS was administered in vivo, SD rats also had a significantly higher IL-6
      response. Hepatocytes from both strains were cultured in the presence of IL-6.
      After three days of culture, alpha 2-Macroglobulin concentrations in the
      supernatants of SD hepatocytes were much higher than those from BN rats. Kupffer
      cell depletion in both BN and SD rats was correlated with a significant increase
      in liver schizont density, but did not abrogate the difference in susceptibility.
      From these results we conclude that the higher cytokine production capacity of SD
      rats compared to BN rats, may contribute to the difference in susceptibility to
      P. berghei sporozoites between these strains, but that other yet unknown factors
      are also involved.

PMID- 8552413
TI  - Specific IgG1 and IgG2 antibody responses of dogs to Leishmania infantum and
      other parasites.
AB  - Sera from dogs naturally infected with Leishmania infantum were analysed for the
      IgG subclass specificity of their antibody response by ELISA. Dogs infected with
      L. infantum produced both IgG1 and IgG2 antibodies with IgG2 being associated
      with asymptomatic infections and IgG1 being associated with disease (symptomatic
      dogs, non- or low-responsive to chemotherapy). The differential responses of IgG1
      and IgG2 serum antibodies in asymptomatic and symptomatic dogs may indicate a
      dichotomous immune response to infection with L. infantum. To confirm this, on a
      broader scale, sera from dogs naturally exposed to an asymptomatic protozoan
      infection, Toxoplasma gondii, were also analysed as were sera from dogs exposed
      to the helminths, Dirofilaria immitis and Toxocara canis. Antibodies specific for
      T. gondii antigen detected in sera from 17 dogs were of the IgG2 subclass only.
      Both IgG1 and IgG2 antibodies to D. immitis and T. canis were present in the sera
      of naturally infected dogs but IgG1 appeared to be the predominant subclass.
      Furthermore, in dogs experimentally infected with T. canis, selective regulation
      of IgG2 and IgG1 responses was apparent since production of the two subclasses
      occurred at different times following infection, with IgG2 levels declining as
      IgG1 levels rose. Thus, the analysis of IgG subsets in parasitized dogs provides
      evidence of a dichotomous response to infection: IgG2 is associated with
      asymptomatic protozoan infections and IgG1 is associated with helminth infections
      and disease caused by protozoan infection.

PMID- 8552414
TI  - Resolution of cryptosporidial infection in mice correlates with parasite-specific
      lymphocyte proliferation associated with both Th1 and Th2 cytokine secretion.
AB  - This study was designed to investigate and characterize T-cell responses which
      lead to elimination of a primary infection of Cryptosporidium muris in BALB/c
      mice. The proliferative response of spleen cells to parasite antigen was measured
      by uptake of 3H-thymidine and, in parallel, supernatants were removed from cells
      to measure levels of IFN-gamma, TNF, IL-2 and IL-4 by ELISA. Oocyst excretion in
      faeces was first detected on day 10 post infection (p.i.); the level of shedding
      subsequently increased until day 14 and then declined until no oocysts were
      detected by day 25. The proliferative response of spleen cells from infected
      animals was similar to control levels up to day 14 p.i. but increased
      significantly on day 21 and was even greater on day 26. IFN-gamma and IL-2 were
      detected initially on day 14 p.i. and significantly higher concentrations were
      found on days 21 and 26. IL-4 secretion was also detected, but not until day 21
      p.i., and production of TNF was not found at any time. Depletion of T-cells or
      CD4+ cells from spleen cells cultured with antigen resulted in a significant
      decrease in the levels of cytokine detected. These results indicated, therefore,
      that in BALB/c mice there was a correlation between the development of immunity
      to C. muris infection and both a parasite antigen-specific proliferative response
      and Th1 and Th2 cytokine production by spleen cells.

PMID- 8552415
TI  - Cellular and humoral immune responses to recombinant antigens in sheep infected
      with Toxoplasma gondii.
AB  - Immune responses to recombinant fragments of the Toxoplasma gondii antigens ROP2
      and GRA2 were investigated in sheep naturally and experimentally infected with T.
      gondii oocysts. Specific serum antibodies to C-terminal fragments were detected
      by ELISA. Cell-mediated responses in peripheral blood mononuclear cells were
      demonstrated by proliferation and interferon-gamma production following in vitro
      stimulation with the ROP2 fragment. This data indicates the presence of epitopes
      for sheep B cells in the recombinant GRA2 fragment and for both B and T cells in
      the ROP2 fragment.

PMID- 8552416
TI  - Protective immunity against malaria: cellular changes in the liver vary according
      to the method of immunization.
AB  - Characterization of cells present in the extravascular compartment of murine
      liver was performed after different immunization procedures against the malaria
      parasite Plasmodium yoelii. Mice were immunized with live or irradiated
      sporozoites or with parasitized erythrocytes. Whatever the immunization protocol
      used, the mice were protected against a sporozoite challenge but each
      immunization procedure induced a specific profile of cell types. Immunization
      with irradiated sporozoite induce a significant increase in CD8+ lymphocytes,
      parasitized erythrocytes stimulates production of monocytes/macrophages and CD8+
      lymphocytes while, after live sporozoites immunization, polymorphonuclear cells,
      macrophages/monocytes, B cells and a range of T cell subsets were increased in
      number.

PMID- 8552417
TI  - Effect of testosterone on the mucosal defence against intestinal helminths in
      Indian soft-furred rats, Millardia meltada with reference to goblet and mast cell
      responses.
AB  - Effects of testosterone on the mucosal defence mechanisms against intestinal
      helminths were examined in Millardia meltada. When female M. meltada were treated
      with testosterone at the pharmacological dose, Nippostrongylus brasiliensis
      infection persisted for over seven weeks with prominent biphasic pattern of
      faecal egg production, whereas almost complete expulsion was observed by two
      weeks in untreated controls. In spite of a biphasic pattern of faecal egg
      production, the worm burden of testosterone-treated animals remained constant up
      to three weeks and then slowly decreased by seven weeks. To see whether or not
      this delayed expulsion in testosterone treated animals was due to altered
      cellular responses of the intestinal mucosa, goblet and mast cell responses were
      examined histologically. At two weeks post-infection, goblet cell responses at
      the infected site were significantly lower in testosterone-treated animals than
      in controls. In contrast mast cell hyperplasia was comparable between
      testosterone-treated and control animals. When Strongyloides venezuelensis, in
      which expulsion is dependent on mucosal mast cells, were infected concurrently
      with N. brasiliensis, testosterone-treated animals could expel S. venezuelensis
      worms by Day 18, but failed to expel N. brasiliensis. Histologically, mast cell
      hyperplasia was associated with expulsion of S. venezulensis, while goblet cell
      responses were suppressed. From these results, testosterone seems to suppress
      proliferation/function of goblet cells but does not affect mast cells of M.
      meltada.

PMID- 8552418
TI  - Reduced amount of intestinal mucus by treatment with anti-CD4 antibody interferes
      with the spontaneous cure of Nippostrongylus brasiliensis-infection in mice.
AB  - Mechanism of spontaneous cure was studied in mice infected with mouse-nonadaptive
      Nippostrongylus brasiliensis. Adult BALB/c mice were cured spontaneously of
      infection with this strain of N. brasiliensis by Day 7 post-infection. Expulsion
      of intestinal worms was delayed dose-dependently by a treatment with anti-CD4
      antibody. However, the treatment had no significant effect on larval recovery
      from the lungs. Treatment of mice with anti-IL-5 antibody suppressed intestinal
      tissue eosinophilia induced by the infection, but did not affect intestinal worm
      recovery. Antigen specific IgE antibody was not detected in the sera obtained
      from Days 5 to 15. Therefore, IL-5 and specific IgE antibody are probably not
      important in the spontaneous cure. Treatment of mice with anti-CD4 antibody had
      no significant effect on number of intestinal goblet cells or on expression of
      terminal sugars of goblet cell mucins. However, histological and quantitative
      analyses revealed that significantly less intestinal mucus was released in anti
      CD4 antibody treated mice than in control mice. These results suggest that CD4+
      lymphocytes control the amount of intestinal mucus and consequently the reduced
      mucus interferes with the spontaneous cure. Quantity of mucus released in the
      intestinal lumen may have an essential role in the spontaneous cure of N.
      brasiliensis-infection of mice.

PMID- 8552420
TI  - Headaches and the primary care pediatrician.

PMID- 8552419
TI  - Assessment of the role of the humoral response to Plasmodium falciparum MSP2
      compared to RESA and SPf66 in protecting Papua New Guinean children from clinical
      malaria.
AB  - The prevalence and concentration of naturally acquired humoral response (IgG) to
      merozoite surface protein 2 (MSP2), RESA, SPf66 and crude schizont extract were
      measured in a population living in a malaria highly endemic area of Papua New
      Guinea. A prospective longitudinal study in 0.5-15 year old children was
      conducted for one year in order to examine the relationship between the humoral
      response to these antigens and subsequent susceptibility to clinical malaria
      using a series of clinical definitions. The prevalence and concentration of
      antibodies to all antigens increased with age. Such correlation with age was most
      marked for MSP2 recombinant proteins. When age and previous exposure were
      controlled for, only antibody levels to MSP2 recombinant proteins (3D7 and d3D7)
      and to RESA predicted a reduction in incidence rate of episodes of clinical
      malaria. Our results support the inclusion of the recombinant proteins of the 3D7
      allelic family of merozoite surface antigen 2 and RESA into a subunit vaccine
      against malaria.

PMID- 8552421
TI  - Comprehensive evaluation and treatment of recurrent pediatric headache.
AB  - Continuity of care with a clinician who has established a therapeutic alliance is
      the most important aspect of recurrent pediatric headache management. The
      provider should assume a concerned and supportive manner that promotes self
      esteem and self-mastery and control. Patient and family efforts to reduce
      functional disability and return to normal activities should be strongly
      reinforced. Treatment regimens should be reviewed for side effects, compliance,
      and perceived efficacy. Behavioral techniques should be reviewed in detail with
      opportunities for the clinician to "trouble shoot" any difficulties encountered
      by the patient. Periods of potentially increased stress (eg, transitions or loss)
      should be anticipated and managed prospectively. The clinician should
      periodically reassess possible psychosocial issues and make appropriate mental
      health referrals. In the long run, regular follow-up by the primary care
      clinician remains the most important factor in the successful management of
      recurrent pediatric headache.

PMID- 8552422
TI  - Pathophysiology of recurrent headaches in children and adolescents.
AB  - The classification and pathophysiology of headache syndromes in children and
      adolescents is reviewed. The most important issues are classifying the headache
      type and determining the etiology of the child's headache. This is best
      accomplished with a thorough history and physical examination, coupled with
      selected laboratory tests. The pathophysiology of the underlying headache as
      reviewed usually will allow the choice of appropriate treatment modalities.

PMID- 8552423
TI  - Psychosocial factors in recurrent pediatric headache.

PMID- 8552424
TI  - Pharmacologic treatment of recurrent pediatric headache.

PMID- 8552425
TI  - Behavioral treatment of pediatric headache.

PMID- 8552426
TI  - Complex behavior of simple repeats: the fragile X syndrome.
AB  - The fragile X syndrome of mental retardation is one of the most common genetic
      diseases. The mutation causing this disease was the first of a new class of
      mutations involving repeat sequences disturbing gene function. Fragile X
      mutations consist of an expansion of a CGG trinucleotide repeat in the FMR1 gene,
      which is inactivated as a result of this expansion. The lack of FMR1 protein is
      believed to be responsible for the mental retardation. The mechanism and the
      timing of the repeat amplification are still not known. Characterization of the
      repeat has clarified the genetics of fragile X syndrome, and has given tools to
      establish the diagnosis and to determine carrier status.

PMID- 8552427
TI  - Reduced cyclic AMP production in fragile X syndrome: cytogenetic and molecular
      correlations.
AB  - The cAMP cascade is an intracellular signal transduction system thought to be
      important for neuronal regulation and information storage. cAMP production is
      reduced in platelets from patients with fragile X syndrome. In the present study
      we assayed cAMP metabolism, Xq27.3 fragile site percentages, size of
      amplification mutation in fragile X mental retardation-1 gene (FMR-1), and FMR-1
      mRNA levels in 21 lymphoblastoid cell lines (LCL) from fragile X patients. cAMP
      production was diminished in fragile X LCL relative to controls (n = 20) when
      cells were assayed in prostaglandin E1 (74%, p < 0.02) and in forskolin (64%, p <
      0.1) although the difference was statistically significant only in prostaglandin
      E1. The length of the FMR-1 amplification mutation correlated with measures of
      cAMP production which were unassociated with receptor activation (r = -0.53, p =
      0.02, and r = -0.48, p = 0.03, for unstimulated and forskolin-stimulated cAMP
      production, respectively). In fragile X LCL, fragile site percentages did not
      correlate with any measure of cAMP production. All fragile X LCL showed absence
      of FMR-1 mRNA. These data suggest that diminished cAMP production in fragile X
      tissues may be linked to the fragile X amplification mutation, either as a result
      of influences of the mutation on FMR-1 expression or on transcription of other
      genes downstream from FMR-1.

PMID- 8552428
TI  - Experimental neuronal injury in the newborn lamb: a comparison of N-methyl-D
      aspartic acid receptor blockade and nitric oxide synthesis inhibition on lesion
      size and cerebral hyperemia.
AB  - The purpose of this study was to compare the effects of dizocilipine maleate (MK
      801) and NG-nitro-L-arginine methyl ester (L-NAME) on focal excitotoxic brain
      injury and associated hemodynamic response in the newborn lamb. A 27 gauge needle
      was placed into the right striatum in 28 anesthetized newborn lambs. Seven
      animals were placed in each group. A negative control group received 0.2 mL of
      buffered saline, a positive control group received 5 mumol of N-methyl-D-aspartic
      acid (NMDA) alone, and two groups received NMDA and pretreatment with L-NAME.
      Ultrasound images and cerebral blood flow determinations (microspheres) were
      obtained before, and at 20, 40, and 60 min after, intrastrial injection. Three
      animals in each group underwent histopathologic evaluation. Sonographic lesions
      were visible immediately after intracerebral injection. Saline injection resulted
      in small lesions (mean volume; 13.6 +/- 5 mm3) without hyperemia. NMDA alone
      resulted in larger lesions (92.9 +/- 24 mm3) and hyperemia to both hemispheres,
      whereas pretreatment with MK-801 reduced lesion size (11.7 +/- 6 mm3) and
      completely ablated cerebral hyperemia. Pretreatment with L-NAME showed no effect
      on lesion size (69.9 +/- 20 mm3) and hyperemia only in the ipsilateral
      hemisphere. Sonographic lesions correlated well with gross and histopathologic
      appearance. We concluded that NMDA-induced focal brain injury and associated
      hyperemia in the newborn lamb appear to be specific NMDA receptor-mediated
      events. NO production probably does not play a major part in NMDA-induced
      neonatal neuronal injury, and may be only partly responsible for regional
      hyperemia during NMDA injection.

PMID- 8552429
TI  - L-NAME reduces infarct volume in a filament model of transient middle cerebral
      artery occlusion in the rat pup.
AB  - The importance of nitric oxide (NO) during focal cerebral ischemia remains
      controversial as studies have suggested both a neurotoxic and neuroprotective
      role. In the 7 d old rat pup, NG-nitro-L-arginine, a nitric oxide synthase
      inhibitor, reduced infarct volume in a model of unilateral carotid ligation with
      2.5 h exposure to 8% O2. The current study examined whether NO is neurotoxic in a
      filament model of transient middle cerebral artery occlusion (MCAO) in the 14-18
      d-old rat pup. We developed a reproducible filament model of transient MCAO in 14
      18-d-old spontaneously hypertensive rats (35 g) by passing a no. 6-0 (0.07-mm)
      nylon filament via the carotid artery to occlude the middle cerebral artery for 4
      h under normoxic conditions. After filament removal and reperfusion for 24 h, we
      determined infarct volume using the mitochondrial stain 2,3,5
      triphenyltetrazolium chloride. NO synthesis was inhibited using NG-nitro-L
      arginine methyl ester (L-NAME) at a dose of 3 mg/kg, intraperitoneally, 1 h
      before MCAO. We measured infarct volume in control (n = 7) and L-NAME (n = 7)
      groups. L-NAME reduced infarct volume by 55% (p < 0.01). In the control group,
      infarct volume (180 +/- 29 mm3) averaged 49 +/- 7% of the left hemisphere (359 +/
      16 mm3). In the L-NAME-treated group, infarct volume (77 +/- 19 mm3) was 22 +/-
      5% of the left hemispheric volume (344 +/- 2 mm3). These findings support earlier
      studies that used models of neonatal hypoxic-ischemic brain injury and suggest a
      neurotoxic role of NO. They extend these observations by demonstrating a
      significant reduction in infarct volume in a stroke model in the immature rat
      pup.

PMID- 8552430
TI  - The dynamics of brain concentrations of phenylalanine and its clinical
      significance in patients with phenylketonuria determined by in vivo 1H magnetic
      resonance spectroscopy.
AB  - Cerebral concentrations of phenylalanine (PHE) were measured by means of
      quantitative in vivo 1H MR spectroscopy in 8 adult patients treated early for
      phenylketonuria type I. A 1.5-Tesla routine magnetic resonance scanner,
      localization sequence with short echo time (20 ms), and a fully automated data
      processing scheme were used. Baseline plasma PHE concentrations were 1.04 (0.70
      1.39) mmol/L PHE with concurrent brain PHE concentrations of 0.27 (0.13-0.41)
      mmol/kg of wet weight resulting in a plasma/brain ratio of 4.12. Plasma and brain
      concentrations correlated significantly (Kendall tau b = 0.91, p < 0.01). During
      an oral load with a single dose of 100 mg L-PHE per kg of body weight in four
      patients, plasma levels steeply increased. Concurrent brain PHE increase was less
      steep, was significantly delayed, and still continued up to 20 h postload.
      Despite the proven rise in plasma and brain concentrations of PHE,
      neuropsychologic examinations revealed no impairment of attentional and fine
      motor abilities from preload up to 20 h postload.

PMID- 8552431
TI  - The effect of rapid thoracoabdominal compressions on intracranial pressure in
      newborn lambs.
AB  - Measurements of forced expiratory flow in infants can be obtained with the rapid
      thoracoabdominal compression (RTC) technique. To assess the transmission of the
      chest wall compression pressure into the cerebrum, we have performed intracranial
      pressure (ICP) measurements during RTCs in newborn lambs. Thirteen lambs were
      studied during the first 8 d of life. An epidural pressure transducer was
      implanted under general anesthesia. Respiratory measurements were performed under
      sedation with ketamine. RTCs were induced through an inflatable jacket wrapped
      around the lamb's trunk. RTCs were started with a pressure of 30 cm H2O. The
      compression pressure was increased in steps of 20 cm H2O up to 250 cm H2O. Flow
      and volume were determined with a pneumotachograph attached to a face mask.
      Transpulmonary pressure (Ptp) was measured with an esophageal balloon placed in
      the lower esophagus. RTCs resulted in proportional increases of Ptp and ICP. ICP
      was lower or equal to Ptp in all measurements. No changes in baseline ICP
      occurred throughout the study period. The maximal ICP observed during RTCs was
      within the range of pressures observed during crying in newborn infants. These
      data suggest that the RTC technique can be considered safe even at high
      compression pressures.

PMID- 8552432
TI  - Surfactant protein B in human fetal lung: developmental and glucocorticoid
      regulation.
AB  - Pulmonary surfactant protein B (SP-B) enhances phospholipid film formation in
      vitro and is essential for normal surfactant function in vivo. We examined human
      fetal lung before and during explant culture for content and cellular
      localization of SP-B mRNA and protein. SP-B mRNA was low in preculture specimens
      (18-20 wk) but hybridization signal increased over epithelial cells during
      culture and was enhanced by dexamethasone treatment (10 nM). SP-B
      immunofluorescence was very low in preculture specimens, increased during
      culture, and was uniformly intense in epithelial cells of dexamethasone-treated
      tissue. With a newly developed immunoassay, SP-B protein was undetectable in
      preculture lung (< 2% of adult), appeared during culture (26% of adult), and was
      further increased approximately 3-fold by dexamethasone treatment (86% of adult);
      lung tissue of two newborn infants contained 7-9-fold more SP-B than is found in
      the adult. Using Western blot with enhanced chemiluminescence, mature SP-B was
      undetectable in 16-wk specimens but was present in 19-24-wk preculture tissue at
      0.2-2.9% of the adult level. By comparison, SP-B mRNA content is 14 and 50% of
      adult level in 19- and 24-wk lung tissue, respectively; levels increase 3-fold
      during culture and a further 3-fold with dexamethasone. Based on these observed
      differences between mRNA and protein content, we conclude that basal SP-B gene
      expression in epithelial cells of human fetal lung is regulated primarily at the
      level of translation or protein stability, whereas glucocorticoids act
      transcriptionally. We speculate that SP-B protein accumulates only as type II
      cells differentiate and acquire lamellar bodies for processing and storage of SP
      B.

PMID- 8552433
TI  - Prenatal dexamethasone and exogenous surfactant therapy: surface activity and
      surfactant components in airway specimens.
AB  - To explain some of the effects of prenatal glucocorticoid treatment on lung
      function, surfactant parameters in the airway specimens of ventilator-dependent
      preterm infants were analyzed. In this double-blind study, the mothers of these
      infants had received dexamethasone (DEX) or placebo prenatally. Human surfactant
      was given for the treatment of moderate to severe respiratory distress syndrome.
      Seventy-six preterm infants with mean gestational age of 29 wk and mean birth
      weight of 1137 g were studied. The concentrations of surfactant components in
      epithelial lining fluid (ELF) were analyzed, and the surface activity was
      measured using a pulsating bubble method. Prenatal DEX treatment increased the
      responsiveness to exogenous surfactant and decreased the severity of respiratory
      failure during the first day of life. The treatment had no effect on the
      concentrations of surfactant phospholipids that were generally high. Prenatal DEX
      treatment increased the association between phospholipid concentration in ELF and
      the degree of respiratory failure. Prenatal DEX improved the surface activity of
      surfactant isolated from airway specimens and tended to increase the ratio of
      surfactant protein A to phosphatidylcholine among recipients of exogenous
      surfactant. A subgroup of infants, offspring of mothers with severe hypertension
      had an abnormally low concentration of surfactant protein A and a poor outcome,
      despite prenatal DEX treatment or surfactant substitution. Prenatal DEX decreased
      the concentration of nonsedimentable proteins in ELF and decreased the inhibition
      of surface activity by these proteins. Our results indicate that improved
      surfactant function during the first day of life explains some of the beneficial
      pulmonary effects of prenatal glucocorticoid treatment in preterm infants who are
      ventilator-dependent.

PMID- 8552434
TI  - The effect of high dose antenatal vitamin E on hypoxia-induced changes in newborn
      rats.
AB  - The protective effects of high dose antenatal vitamin E on hypoxemia in newborn
      rats were investigated. The subjects were 1-d-old Wistar rats weighing 5-6 g
      which were born to mothers weighing 245-250 g. Three groups of rat pups, each
      consisting of eight newborn rats, were used: nontreated control group, hypoxic
      group, and vitamin E group. The mothers of pups in the last group were given
      vitamin E (2000 mg/kg/d) antenatally on 3 consecutive days. Hypoxia was induced
      by breathing of a mixture of 8% oxygen and 92% nitrogen for 3 h. Then pups were
      allowed to inhale normal atmospheric air for 30 min. All rats were killed on the
      first day of life after the procedure of hypoxia and reoxygenation. The brains,
      lungs, livers, intestines, and kidneys were studied biochemically and
      histopathologically. The hypoxia-induced biochemical changes were determined by
      measuring lipid peroxidation and myeloperoxidase activity. Vitamin E effectively
      inhibited hypoxia-induced lipid peroxidation in liver and intestines, and
      decreased the levels of thiobarbituric acid-reactive substances in brain. In
      agreement with lipid peroxidation, tissue associated myeloperoxidase activity was
      increased in liver, intestines, and kidneys, but not in brain and lungs, of the
      hypoxic group. Histopathologic changes in intestines were epithelial separation
      and submucosal polymorphonuclear leukocyte infiltration. In the liver, leukocyte
      infiltration was observed only near the portal areas. These changes were not
      observed in the vitamin E group. It was concluded that high doses of antenatal
      vitamin E may protect the newborn rat pups against hypoxia-induced tissue injury.

PMID- 8552435
TI  - Lung hypoplasia can be reversed by short-term obstruction of the trachea in fetal
      sheep.
AB  - Our aim was to determine whether an existing lung growth deficit could be
      reversed, in utero, by short-term (6 d) obstruction of the fetal trachea.
      Chronically catheterized fetal sheep (term approximately 145 d) were divided into
      four groups: 1) no treatment (control); 2) continuous lung liquid drainage to
      induce lung hypoplasia (105-134 d, drain); 3) lung liquid drainage to induce lung
      hypoplasia (105-128 d), followed by restoration of tracheal flow (128-134 d,
      drain and reconnect); and 4) lung liquid drainage to induce lung hypoplasia (105
      128 d), followed by tracheal occlusion to accelerate lung growth (128-134 d,
      drain and obstruct). Lung liquid volumes and secretion rates were measured on d
      125, 130, and 134 of gestation and postmortem data collected on d 135. Compared
      with controls, continuous lung liquid drainage (drain) significantly reduced wet
      lung weights (34.3 +/- 2.6 g/kg versus 13.3 +/- 1.4 g/kg) and total lung DNA
      contents (177 +/- 11 mg/kg versus 94 +/- 7 mg/kg). Reestablishing tracheal flow
      for 6 d (drain and reconnect) increased fetal lung wet weights (19.2 +/- 1.6
      g/kg), but not total DNA contents (106 +/- 9 mg/kg), compared with lung liquid
      drained fetuses (drain). After 6 d of tracheal obstruction (drain and obstruct)
      lung liquid volumes, wet lung weights, and total protein contents (weight, 28.6
      +/- 2.8 g/kg; protein, 1376 +/- 97 mg/kg) were similar to control values (weight,
      34.3 +/- 2.6 g/kg; protein, 1506 +/- 123 mg/kg); lung DNA contents were less than
      control but greater than values from lung liquid drained fetuses (drain and
      obstruct, 140 +/- 9 mg/kg versus drain, 94 +/- 7 mg/kg). We conclude that
      obstruction of the trachea can reverse an existing fetal lung growth deficit in
      approximately 6 d, whereas merely restoring tracheal continuity does not increase
      fetal lung growth.

PMID- 8552436
TI  - Smooth muscle myosin heavy chain isoforms are developmentally regulated in male
      fetal and neonatal sheep.
AB  - Adult vascular smooth muscle expresses 204-kD (SM1) and 200-kD (SM2) myosin heavy
      chain (MHC) isoforms. Fetal vascular smooth muscle expresses another 200-kD
      isoform, MHC-B, that appears to be developmentally regulated. The ontogeny of
      expression of these MHC isoforms in vascular and nonvascular smooth muscles is
      not fully understood and may differ. In the present report we examined the
      ontogeny of these isoforms in aortic and bladder smooth muscle from male fetal (n
      = 12, 119-140-d gestation; term 145 +/- 5 d) and neonatal (n = 12, 1-33 d) sheep.
      Tissues were analyzed for total and soluble protein contents. Actin, MHC, and MHC
      isoforms were analyzed by SDS-PAGE using 3-20% and 4% polyacrylamide gels,
      respectively. The expression of the adult and fetal 200-kD MHC isoforms were
      determined by Western analysis. Between 119 d gestation and 33 d neonatal, age
      dependent increases (p < 0.02) occurred in bladder actin (16 +/- 0.8 versus 22 +/
      1.4 micrograms/mg of wet weight), MHC (6.5 +/- 0.2 versus 9.7 +/- 1.1) and both
      soluble (71 +/- 2.9 versus 92 +/- 6.3) and total protein (78 +/- 3.9 versus 103
      +/- 5.5). Aortic smooth muscle actin (8.5 +/- 0.7 versus 17 +/- 1.1), MHC (3.1 +/
      0.4 versus 5.2 +/- 0.5), and soluble (44 +/- 2.3 versus 61 +/- 3.0) and total
      protein (87 +/- 5.8 versus 108 +/- 3.2) also increased (p < 0.01). Aortic SM1
      increased (r = 0.79, p < 0.001) during this time, whereas expression of the 200
      kD MHC fell (r = -0.79, p < 0.001). In contrast, bladder SM1 fell (r = -0.88, p <
      0.001) as the 200-kD MHC rose (r = 0.88, p < 0.001). The type of 200-kD MHC
      isoform expressed also differed between tissue types; bladder expressed SM2 and
      little or no MHC-B throughout this phase of development, whereas fetal aorta
      appeared to express primarily MHC-B, which decreased as adult SM2 expression rose
      after birth. Expression of smooth muscle proteins and MHC isoforms are
      developmentally regulated and tissue-dependent, the latter perhaps reflecting
      developmental differences in organ growth and/or function.

PMID- 8552437
TI  - Effect of an interleukin-1 receptor antagonist on the hemodynamic manifestations
      of group B streptococcal sepsis.
AB  - IL-1 is purported to be a proximal mediator in the cascade leading to septic
      shock. To characterize its hemodynamic effects and to ascertain whether its
      blockade would ameliorate the deleterious consequences of sepsis, an IL-1
      receptor antagonist (IL-1ra) was administered to 16 anesthetized, mechanically
      ventilated piglets that received a continuous infusion of group B streptococci
      (GBS) (7.5 x 10(7) colony-forming units/kg/min). Systemic (Psa), pulmonary artery
      (Ppa), and wedge (Pwp) pressures and cardiac output were measured pre-GBS and
      every 30 min during GBS infusion. After 15 min of bacterial infusion the control
      group received normal saline, whereas the treatment group received a bolus of IL
      1ra (40 mg/kg) followed by a continuous infusion of IL-1ra (60
      micrograms/kg/min). In comparing IL-1ra-treated animals with controls from the 15
      min GBS baseline to the succeeding septic study period (45-120 min), the
      following treatment effects were noted (120-min values shown): mean Psa remained
      elevated in treatment compared with control animals (12.7 +/- 2.5 versus 9 +/-
      3.5 kPa; p < 0.001) as did CO (0.21 +/- 0.07 versus 0.13 +/- 0.08 L/min/kg; p <
      0.001). Pwp decreased in the treatment compared to the control group over the
      study period (1 +/- 0.3 versus 1.6 +/- 0.7 kPa; p < 0.02). Mean Ppa and mean Pra
      were not different between groups over time. Median length of survival was
      significantly longer (p = 0.04) in treated (226 min) compared with control
      animals (150 min). These data suggest that IL-1 plays an important role in GBS
      sepsis and septic shock, and that IL-1ra may in part ameliorate the
      cardiovascular alterations associated with GBS sepsis in the neonate.

PMID- 8552438
TI  - Postnatal cardiovascular and metabolic responses to a single intramuscular dose
      of betamethasone in fetal sheep born prematurely by cesarean section.
AB  - Although the benefits of antenatal hormone treatment are well accepted, most
      studies have reported only pulmonary effects. There is evidence of beneficial
      cardiovascular and metabolic effects in studies using chronically catheterized
      animals; however because of the route of administration, the results are not
      directly applicable to clinical strategies. We previously demonstrated
      significant pulmonary effects in animals treated antenatally with a single,
      direct fetal, intramuscular injection of glucocorticoids. This study was
      performed to determine the effects of a single fetal injection of betamethasone
      (BETA) alone or in combination with thyroxine (T4) on cardiovascular and
      metabolic responses after preterm birth. Hemodynamic and metabolic responses at
      birth were determined in fetuses (126-d gestation; term = 150 d) treated with
      ultrasound-guided intramuscular injections of 0.5 mg/kg BETA (n = 7), BETA plus
      60 g/kg T4 (n = 7), or saline (SAL, n = 9). After 48 h, lambs were delivered by
      cesarean section and studied for 3 h. BETA treatment increased mean arterial
      blood pressure [56 +/- 6 (SEM) versus 42 +/- 3 mm Hg], heart rate (152 +/- 5
      versus 123 +/- 4 beats/min), and cardiac output (467 +/- 17 versus 349 +/- 36
      mL/min/kg) versus SAL. Responses of BETA+T4-treated animals were not different
      from animals treated with BETA alone. Glucose and FFA were similar among all
      groups. The increase in catecholamine levels normally seen at birth was
      significantly attenuated in both the BETA and BETA+T4-treated animals. A single,
      intramuscular injection of glucocorticoids 48 h before delivery improves
      cardiovascular responses to preterm birth. This effect is not augmented by
      concomitant administration of T4.

PMID- 8552439
TI  - Bone marrow fibroblasts from children with aplastic anemia exhibit reduced
      interleukin-6 production in response to cytokines and viral challenge.
AB  - Defects of the bone marrow microenvironment have been implicated in the
      pathogenesis of aplastic anemia (AA). We examined granulocyte/macrophage colony
      stimulating factor (GM-CSF) and IL-6 production in bone marrow fibroblasts from
      five children with AA in response to cytokines and viral challenge with
      cytomegalovirus (CMV). Cytokine-stimulated IL-6 production in patients'
      fibroblasts was significantly reduced, whereas GM-CSF production was found to be
      comparable to normal controls. Also, CMV-mediated stimulation of IL-6 production
      was significantly lower in bone marrow fibroblasts from patients with AA. During
      the late phase of CMV-infection, IL-6 production was suppressed in CMV-infected
      fibroblasts from patients with AA with 90% inhibition of IL-6 protein production
      and marked reduction in IL-6 mRNA accumulation. Defective IL-6 production in bone
      marrow fibroblasts might contribute to hematopoietic suppression in some patients
      with AA.

PMID- 8552440
TI  - Role of endogenous atrial natriuretic peptide in chronic anemia in the ovine
      fetus: effects of a non-peptide antagonist for atrial natriuretic peptide
      receptor.
AB  - Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated
      with increased fetal diuresis and natriuresis. To determine the role of atrial
      natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we
      studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate
      cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented
      unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic
      hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d
      of hemorrhage ANP concentrations increased (45 +/- 7 to 234 +/- 15 fmol/mL).
      Hematocrit and arterial blood oxygen content were significantly lower in the
      anemic compared with the nonanemic fetuses (13.8 +/- 0.7 versus 34.6 +/- 2.3% and
      0.7 +/- 0.1 versus 2.6 +/- 0.2 mmol/L). Before HS urine flow rate, urinary sodium
      excretion, fractional excretion of sodium, and renal blood flow were increased in
      the anemic fetuses, and the extracellular fluid volume (inulin space) was
      increased (674 +/- 94 versus 497 +/- 71 mL/kg). However, GFR was not different
      between the groups. HS caused a significant increase in the central venous
      pressure of the anemic fetuses (0.49 +/- 0.03 to 0.70 +/- 0.05 kPa). Urinary
      excretion of cGMP was considered to be a marker of endogenous ANP renal effect
      and was measured before and after a single bolus of HS (5.2 +/- 0.30 mg/kg). HS
      decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and
      nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and
      anemic fetuses (0.48 +/- 0.13 to 0.25 +/- 0.06 and 1.30 +/- 0.66 +/- 0.06
      mL/min). Sodium excretion decreased in both groups after HS (19 +/- 5 to 9 +/- 2
      and 83 +/- 16 to 39 +/- 5 mumol/min). GFR decreased after HS (3.0 +/- 0.8 to 2.4
      +/- 0.5 and 3.6 +/- 0.3 to 2.6 +/- 0.2 mL/min. Fraction excretion of sodium also
      decreased in both groups after HS (4.6 +/- 2.7 to 2.7 +/- 0.5 and 16.1 +/- 2.4 to
      11 +/- 1.6). Percent decreases in urine flow, sodium excretion, GFR, and
      fractional excretion of sodium observed in the anemic fetuses were not
      statistically different from the nonanemic fetuses. Urine flow and sodium
      excretion did not decrease to control levels after HS, suggesting that factors in
      addition to ANP contribute to the natriuresis seen with chronic anemia. After HS
      a transient increase in renal blood flow was observed in the nonanemic fetuses.
      An immediate and sustained further increase in renal blood flow was observed in
      the anemic fetuses (336 +/- 37 to 436 +/- 58 mL/min/100 g of kidney). Decreasing
      GFR and increasing renal blood flow suggests HS may alter the renal
      microcirculation by reversing ANP-induced constriction of the glomerular efferent
      arteriole. We conclude that sustained increases of the central venous pressure
      suggest that ANP inhibition results in decreased fluid movement into perivascular
      tissue. Endogenous ANP may help to maintain basal renal function in the normal
      fetal kidney and participates in the renal adaptation to chronic fetal anemia.
      ANP may promote urine flow and sodium excretion by its effects on both the renal
      microcirculation and the sodium reabsorptive capacity of the nephron.

PMID- 8552441
TI  - Effects of recombinant human erythropoietin on fetal and adult hemoglobin in
      preterm infants.
AB  - In the present study we assess the effect of recombinant human erythropoietin (r
      HuEpo) upon levels of fetal Hb (HbF) and adult Hb (HbA) in preterm infants.
      Twenty-eight "healthy," appropriate for gestational age infants with birth
      weights 900-1400 g entered the study at 3 wk of age. Fourteen infants were
      randomized to receive r-HuEpo, and 14 infants served as controls. Four controls
      and six r-HuEpo treated infants had been transfused before study start, whereas
      four control infants were transfused in the course of the study. The untransfused
      infants showed a high HbF/Hb ratio during the study with only a weak tendency to
      decline toward the expected time of delivery. The total Hb mass increased (p <
      0.05) more in the r-HuEpo-treated infants than in the untreated, whereas the rise
      in HbF mass was similar in the two groups. After each transfusion, the HbF/Hb
      ratio reverted gradually to the ratio expected at the infant's postconceptional
      age. There was no difference in the production rate of HbF between r-HuEpo
      treated infants and controls. The present data indicate that the HbF/HbA ratio in
      preterm infants is subject to the same programmed mechanisms which govern
      intrauterine erythropoiesis until term and that exogenous r-HuEpo does not
      influence this pattern significantly.

PMID- 8552442
TI  - Growth in full-term small-for-gestational-age infants: from birth to final
      height.
AB  - Intrauterine growth retardation, or being small for gestational age (SGA), has a
      life-long impact on a fetus's potential for development and survival. The
      incidence and relative risk of short stature in children born SGA were studied
      using a Swedish healthy full-term (37-43 wk of gestation) singleton birth cohort
      (n = 3650) from Goteborg, followed from birth to final height at about 18 y of
      age. Most infants, defined as SGA on the basis of a birth length less than -2
      standard deviation scores (SDS) below the mean (SGAL infants), showed catch-up
      growth during the first 6 mo after birth, and by 1 y only 13.4% of the SGAL
      infants were below -2 SDS in height. This percentage decreased further during
      childhood to reach a value of 7.9% at 18 y of age. Although most SGAL infants
      have catch-up growth in early life, those who do not constitute 21% of short,
      prepubertal children. At 18 y of age, 22% of the total short population were
      short at birth (< -2 SDS), whereas when birth weight was used to define SGA, only
      14% of the 18-y-old short population were light at birth. SGAL infants were found
      to have a 7-fold higher risk for short final stature (relative risk, 7.1; 95%
      confidence interval, 3.7-13.6) in comparison with the non-SGAL group. In a
      multiple linear regression analysis, both birth length and mid-parental height
      were found to be significantly related to the magnitude of catch-up growth from
      birth to 18 y of age. Neither the length of gestation nor birth weight showed
      such a relationship. It is concluded that the vast majority (> 86%) of "healthy"
      full-term singleton SGAL infants will achieve catch-up in height during the first
      6-12 mo of life, and that this is almost independent of whether birth weight or
      birth length is used to define SGA. Of the remaining, non-catch-up SGA infants,
      about 50% remain short in final height, and thus constitute a high risk group for
      persistent short stature.

PMID- 8552443
TI  - Low vitamin B6 status associated with slow growth in healthy breast-fed infants.
AB  - To evaluate the effect of vitamin B6 status on infant growth, we studied
      longitudinally anthropometry and the erythrocyte parameters that reflect long
      term vitamin B6 status [erythrocyte pyridoxal 5'-phosphate concentration (EPLP),
      erythrocyte aspartate transaminase basal activity (EAST0), and its activation co
      efficient (alpha EAST)] in 44 infants. The infants were exclusively breast-fed
      for 6 mo, given additional solids according a uniform schedule from 6-9 mo, and
      formula after 9 mo, if needed. In seven of these infants, a low vitamin B6 status
      (EPLP < 10th, and EAST0 > 10th or alpha EAST > 90th percentile for these values
      in reference infants) was observed between 4 and 6 mo of age. These seven infants
      showed slower length velocity (0.30 +/- 0.05 versus 0.40 +/- 0.02 mm/d, p < or =
      0.02) and deeper fall in length-for-age (-0.69 +/- 0.20 versus -0.25 +/- 0.07 SD
      score, p < or = 0.03) from 6 to 9 mo of age than the similarly fed infants with
      higher vitamin B6 status. Preceding vitamin B6 status remained a significant
      explanatory factor for length velocity and change in length-for-age in addition
      to preceding and concomitant weight velocity, when sex, birth size, preceding
      length gain, and mid-parent height were taken into account. Change in weight-for
      age alone explained 16% and 18% and, together with vitamin B6 status, 23 and 27%
      of the variation in length velocity and in change in length-for-age,
      respectively. Thus, in healthy breast-fed infants, according to our results, low
      vitamin B6 status is associated with reversibly reduced gain in length.

PMID- 8552444
TI  - Long-term alterations in growth hormone and insulin secretion after temporary
      dietary protein restriction in early life in the rat.
AB  - Protein malnutrition early in life stunts subsequent physical growth in both
      humans and rats, but the mechanism(s) is unknown. To test the hypothesis that
      temporary early life dietary protein restriction produces long-term alterations
      in the growth hormone (GH) neuroendocrine axis, we examined the effects of 3 wk
      of exposure to dietary protein restriction in male rats postweaning (3-6 wk of
      age) on spontaneous and GH-releasing factor (GRF)-stimulated GH secretion at 12
      wk of age. In comparison to rats weaned onto a normal diet (23% protein), rats
      weaned onto a low (4%) protein diet failed to catch up growth when transferred to
      the normal diet between 6 and 12 wk of age. Spontaneous 6-h GH secretory profiles
      of adult rats fed the low protein diet early in life showed a 41% reduction in
      mean GH peak amplitude and a significant suppression in overall mean 6-h plasma
      GH concentrations (37.5 +/- 4.5 versus 56.9 +/- 5.9 micrograms/L; p < 0.02). The
      magnitude of the GH response to 1 microgram of rat GRF(1-29)NH2 i.v. challenge
      was augmented during the GH trough period in these rats (165.7 +/- 30.4 versus
      43.9 +/- 17.6 micrograms/L; p < 0.01). Although basal plasma IGF-I levels and
      glucose tolerance of protein-deprived rats were normal at 12 wk of age, the
      insulin response to ip glucose was severely blunted [insulin integrated area
      under the curve: 303.0 +/- 32.7 versus 778.3 +/- 105.0 pmol/L/75 min; p < 0.01].
      These results demonstrate that temporary protein malnutrition early in life 1)
      blunts spontaneous pulsatile GH secretion, 2) augments GH responsiveness to GRF
      challenge, and 3) reduces the insulin secretory response to glucose in adulthood.
      Our findings suggest that dietary protein in early life is an important
      determinant for CNS control of GH secretion as well as for the development of
      pancreatic beta-cell sensitivity to glucose. Such alterations in the GH
      neuroendocrine axis, together with the subnormal insulin secretion, likely
      contribute to the lack of catch-up growth in this model.

PMID- 8552445
TI  - Glucose suppression of insulin secretion in chronically hyperglycemic fetal
      sheep.
AB  - Previous observations in fetal sheep indicate that glucose may inhibit as well as
      enhance insulin secretion. To study conditions involved in inhibition of insulin
      secretion, we compared changes in plasma insulin concentration in response to
      acute increases in glucose and arginine concentrations in a group of normal, late
      gestation fetal sheep (euglycemic controls, EC) and a comparable group made
      chronically hyperglycemic by constant maternal glucose infusion (hyperglycemics,
      HG). After 7-10 d of maternal and fetal hyperglycemia, fetal glucose
      concentrations (G) were significantly increased in the HG group (0.98 +/- 0.07 mM
      EC, 2.00 +/- 0.11 mM HG, p < 0.001) but fetal plasma insulin concentrations (I)
      were not significantly different (57 +/- 7 pM EC, 71 +/- 9 pM HG, p = 0.2).
      Furthermore, the I/G ratio was significantly decreased in the HG group (60 +/- 9
      EC, 40 +/- 4 HG, p = 0.03) and during a hyperglycemic glucose clamp (delta G
      approximately equal to 1.4 mM), glucose-stimulated increase in steady state I was
      less in the HG than in the EC fetuses (mean delta I/delta G = 106 +/- 15 EC, 61
      +/- 10 HG, p = 0.01). An arginine infusion at the end of the clamp produced
      similar increases in I in the EC and HG groups (delta I = 824 +/- 116 pM EC, 906
      +/- 131 pM HG, p = 0.45). There were no differences between groups for blood
      oxygen saturation and content, pH, or lactate concentration. After 14-17 d of
      hyperglycemia, glucose-stimulated increase in I was even more reduced in the HG
      fetuses than observed at 7-10 d. Decreased insulin response to arginine also was
      present, although pancreatic insulin concentration was not decreased. Glucose
      stimulated increase in I returned to normal after 7 d of no glucose infusion and
      euglycemia. These data indicate that glucose-stimulated insulin secretion is
      reversibly decreased by marked, chronic hyperglycemia. Because pharmacologic
      inhibitors of insulin secretion (e.g. streptozotocin or alloxan) were not used,
      and oxygenation, pH, and lactate values were similar between the two groups, this
      decrease of insulin secretion appears to be glucose-specific, although mechanisms
      involved can include both glucose and amino acid (arginine) stimulation
      processes. Such decrease in fetal insulin secretion may limit the rate of fetal
      glucose utilization during chronic hyperglycemia and thereby modulate the rate of
      fetal growth.

PMID- 8552446
TI  - Comparison of growth hormone and insulin-like growth factor-I regulation of
      estradiol and progesterone production in human luteinized granulosa cells.
AB  - Growth hormone (GH) appears to affect the timing of puberty in children. The
      effects of GH on puberty may be related to direct GH action on ovarian function
      or may be mediated by IGF-I. To determine the likelihood that GH has direct
      effects on ovarian function, we compared the ability of GH and IGF-I to increase
      luteinized granulosa cell steroidogenesis in the absence and presence of
      gonadotropins. Cells were obtained from women undergoing in vitro fertilization
      for tubal disorders or male factor infertility and were placed in static culture.
      GH alone failed to alter progesterone or estradiol accumulation in the medium of
      cultured luteinized granulosa cells. IGF-I produced no increase in progesterone
      accumulation but increased estradiol accumulation 5.6-fold compared with cells
      treated with vehicle. The combination of GH and FSH produced an 0.83-fold
      increase in estradiol accumulation, whereas the combination of IGF-I and FSH
      resulted in a 2.9-fold increase in estradiol accumulation above FSH alone. Thus
      the direct effects of GH on granulosa cell steroid synthesis are modest compared
      with those of IGF-I. If GH has an effect on ovarian development at puberty, it is
      likely to be mediated by a GH-induced increase in circulating IGF-I.

PMID- 8552447
TI  - Perinatal nitric oxide synthase inhibition retards neonatal growth by inducing
      hypertrophic pyloric stenosis in rats.
AB  - Administration of the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine
      methyl ester (L-NAME) during pregnancy has been shown to compromise fetal growth.
      This study was designed to determine whether aminoguanidine, a predominate
      inhibitor of inducible NOS, affects fetal outcome. In addition, we extended the
      prenatal administration of L-NAME into the postnatal period (14 d) to determine
      whether neonatal growth and maturation were also affected. L-NAME, but not
      aminoguanidine, compromises fetal and placental growth. When compared with
      control 14-d-old pups, postnatal L-NAME compromised neonatal growth, whether it
      was given directly (intraperitoneally) (39.7 +/- 1.1 versus 24.1 +/- 1.0 g) or
      indirectly (38.6 +/- 0.5 versus 22.2 +/- 1.2 g) via maternal breast milk.
      Neonatal growth retardation was asymmetric, with brain sparing, suggesting a
      nutritional origin. L-NAME administration resulted in growth retardation that
      extended into adulthood, without evidence of catch-up growth. Treated neonates
      displayed the hallmarks of hypertrophic pyloric stenosis. Significant increases
      in stomach weight/pup weight (9.9 +/- 0.3 versus 8.2 +/- 0.4 x 10(3)) and stomach
      volume/pup weight (12.0 +/- 0.6 versus 9.4 +/- 0.6 mL/100 g) with a concomitant
      decrease in small intestine weight/length (2.10 +/- 0.08 versus 3.18 +/- 0.13
      g/100 cm) was noted in treated versus control pups (p < 0.05). Muscularis
      hypertrophy at the pyloric sphincter in the L-NAME-treated pups was noted by
      histology. Blood pressure was elevated in the L-NAME-treated pups (93 +/- 6
      versus 60 +/- 5 mm Hg in control pups, p < 0.05). These findings are consistent
      with inhibition of neuronal and endothelial NOS activity. We conclude that NO,
      formed via the constitutive isoforms of NOS, is a critical determinant of fetal
      and neonatal growth and maturation.

PMID- 8552448
TI  - Pathways of serine and glycine metabolism in primary culture of ovine fetal
      hepatocytes.
AB  - Previous in vivo studies in the ovine fetus have demonstrated net serine
      production by the fetal liver, a pattern not seen in the adult sheep. The goal of
      this study was to determine the major metabolic pathways responsible for fetal
      hepatic serine production by using stable isotope methodology in primary culture
      of late gestation ovine fetal hepatocytes. Specifically selected tracers of
      glycine were added to individual cultures, with production of labeled serine
      determined after 24 h of incubation. When [1-13C1]glycine or [2-13C1]glycine was
      used as the initial tracer, serine enrichment at 24 h indicated that
      approximately 30% of serine production comes from glycine. Quantitative
      comparison of serine enrichment from these two tracers suggests that serine
      synthesis from glycine occurs via the combined action of the glycine cleavage
      enzyme system (GCE) and serine hydroxymethyltransferase (SHMT). Using [1,2
      13C2(15)N1]glycine as the tracer, there was no significant increase in M + 2
      glycine in the medium over 24 h, suggesting no reversible transamination of
      glycine, and therefore no significant movement of glycine through the glyoxalate
      pathway. These data demonstrate that in primary culture of fetal ovine
      hepatocytes, approximately 30% of serine biosynthesis is derived from glycine,
      primarily via the combined action of GCE and SHMT.

PMID- 8552449
TI  - Flow-induced dilation in newborn intestine.
AB  - The goal of these experiments was to determine the presence and mechanistic basis
      of flow-induced dilation in mesenteric artery from 3-d-old swine. In the first
      experiment, in vitro gut loops were perfused from a blood-filled reservoir under
      controlled-flow conditions, and flow was progressively increased from
      approximately 40% to approximately 170% in six increments by manipulation of pump
      speed. Under control conditions, vascular resistance significantly decreased
      after each step increase in flow rate. NG-Monomethyl-L-arginine (LNMMA; 10(-4)
      M), an arginine analog that blocks nitric oxide production, eliminated this flow
      induced dilation, but only for the step increases in flow at rates above the
      baseline flow rate. For step increases below the baseline rate, LNMMA caused a
      simple parallel shift of the resistance-flow rate curve upward. Phenylephrine
      (10(-6) M), an alpha 1-agonist which has no effect on nitric oxide production or
      half-life, did not eliminate flow-induced dilation, but instead caused a simple
      parallel shift of the resistance-flow rate curve upward across the entire range
      of flows studied. In the second experiment, a 3-cm segment of mesenteric artery
      was perfused with Krebs buffer at two flow rates: 10 and 25 mL/min. The effluent
      from the mesenteric artery segment was suffused onto a deendothelialized,
      phenylephrine-precontracted ring of swine carotid artery; relaxation of this
      bioassay vessel served as an index of release of relaxing factors from the
      mesenteric artery segment. Under control conditions, increase in the mesenteric
      artery flow rate caused a 60% relaxation of the bioassay vessel. This effect was
      eliminated by the addition of LNMMA to the buffer (10(-4) M), but not by the
      addition of indomethacin (10(-5) M). Flow-induced dilation occurs in the
      mesenteric artery of 3-d-old swine. This vascular phenomenon appears to be
      mediated by nitric oxide, but only at flows above the baseline flow rate. The
      mechanism(s) responsible for this phenomenon at lower flow rates is not clear.

PMID- 8552450
TI  - Adhesion of human neuroblasts to HIV-1 tat.
AB  - Several neuropathologic findings in infants and children with human
      immunodeficiency virus type-1 (HIV-1) infection are different from those observed
      in adults, probably related to the fact that the retroviral infection occurs in
      the setting of neuro-development. This report describes the interaction and
      biologic activity of tat, the HIV-1 trans-activating protein on human
      neuroblasts. Two human neuroblastoma cell lines, LAN-5 and GI-CA-N, have been
      studied for their capability to adhere to tat (full recombinant protein) and to
      two different peptide residues of it. Both cells adhere to tat and tat46-60 basic
      domain, although not to tat65-80 residue, which contains the RGD (arginine
      glycine-aspartic acid) motif. Adhesion to collagen I was inhibited by
      preincubating GI-CA-N cells with tat,46-60 although not with tat,65-80 indicating
      the capability of the basic residue to interfere with collagen I-induced cellular
      adhesion. The expression of 200-kD neurofilaments induced by collagen I was not
      induced by tat,46-60 indicating that neural differentiation along the same
      pathway is not mimicked by this peptide. Neuroblast cell proliferation was not
      affected by adhesion to tat46-60 nor to tat.65-80 GI-CA-N cells are not
      permissive to HIV-1 infection. However, proviral DNA was documented in the cell
      lysate for 14 consecutive in vitro passages, whereas HIV-1 transcription was
      never detectable. This would exclude the possibility that tat would be transduced
      by these cells. GI-CA-N stained negative for CD4, although positive for Gal-C,
      which may explain HIV-1 entry. Results show that immature human neural cells
      interact with tat protein and/or its basic residue in vitro. A mechanism similar
      to that herein described would possibly be active in vivo, which may help in
      clarifying the pathogenic mechanisms of neurologic dysfunction and destruction of
      the CNS observed in infants infected with HIV-1.

PMID- 8552451
TI  - Tumor markers CA 125 and CA 19-9 in cord blood and during infancy: developmental
      changes and use in pediatric germ cell tumors.
AB  - Tumor markers CA 125 and CA 19-9 are elevated in a variety of malignancies in
      adult patients, but only little is known of their biology during gestation or
      infancy. We have addressed the developmental pattern of these carbohydrate
      antigens in pediatric patients by measuring their serum levels in 133 cord blood
      samples from the second through third trimester of gestation and in 39 infants
      aged less than 1.5 y. The serum concentrations of both markers revealed
      developmental changes, the levels being higher at earlier gestation (wk 24
      through 37) than at term or during infancy. The clinical value of the markers was
      evaluated by monitoring 26 children with germ cell tumors; 14 benign and 2
      immature teratomas, and 11 malignant germ cell tumors. Patients with immature
      sacrococcygeal teratomas showed constant and prolonged elevations of serum CA 125
      and CA 19-9. In contrast, all but two children with mature teratomas had normal
      marker levels; these two patients with abnormally high serum CA 125 and CA 19-9
      values for the first 4 postoperative weeks had a benign ovarian and ventricular
      teratoma, respectively. Of the 11 children with malignant germ cell tumors, serum
      CA 125 or CA 19-9 concentration was elevated in four patients at diagnosis and
      declined to normal within 2 wk after institution of therapy. Malignant recurrence
      in two patients was not associated with a reelevation of the CA 125 level. Taken
      together, our results demonstrate a developmentally regulated pattern of serum CA
      125 and CA 19-9. The carbohydrate markers were usually inferior to alpha
      fetoprotein in monitoring of germ cell tumors, but may be a useful adjunct in the
      follow-up of immature teratomas.

PMID- 8552452
TI  - Late effects among long-term survivors of childhood acute leukemia in The
      Netherlands: a Dutch Childhood Leukemia Study Group Report.
AB  - Late events and side effects are reported in 392 children cured of leukemia. They
      originated from 1193 consecutively newly diagnosed children between 1972 and
      1982, in first continuous complete remission for at least 6 y after diagnosis,
      and were treated according to Dutch Childhood Leukemia Study Group protocols
      (70%) or institutional protocols (30%), all including cranial irradiation for CNS
      prophylaxis. Data on late events (relapses, death in complete remission, and
      second malignancies) were collected prospectively after treatment; late side
      effects were retrospectively collected by a questionnaire, completed by the
      responsible pediatrician. The event-free survival of the 6-y survivors at 15 y
      after diagnosis was 92% (+/- 2%). Eight late relapses and nine second
      malignancies were diagnosed, two children died in first complete remission of
      late toxicity of treatment, and one child died in a car accident. The most
      important long-term side effects reported were learning disabilities (50%), short
      stature, obesity, and delayed pubertal development. No increase in the incidence
      of cardiovascular, pulmonary, urogenital, or gastrointestinal tract diseases or
      an increased vulnerability of the musculoskeletal system was found. However,
      prolonged follow-up is necessary to study the full-scale late effects of
      cytostatic treatment and radiotherapy administered during childhood.

PMID- 8552453
TI  - The effect of asphyxia on the pharmacokinetics of ceftazidime in the term
      newborn.
AB  - The multiple-dose pharmacokinetics of ceftazidime (CAZ) (administered twice daily
      in a 50 mg/kg of body weight i.v. dose) were studied in 10 severely asphyxiated
      term infants with suspected septicemia on d 3 of life. Nine term infants with
      suspected septicemia but without asphyxia served as controls. Blood samples were
      collected from an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an i.v.
      bolus injection. A high performance liquid chromatography method was used to
      determine CAZ concentrations from serum. CAZ pharmacokinetics followed a one
      compartment open model. The GFRs of all infants were simultaneously studied by
      means of the 24-h continuous inulin infusion technique. Elimination serum half
      life (5.86 +/- 1.13 h versus 3.85 +/- 0.40 h) and serum trough concentrations (46
      +/- 14 mg/L versus 23 +/- 7 mg/L) of CAZ were significantly (p < 0.001) increased
      in the asphyxiated newborn, whereas total body clearance of CAZ (128.4 +/- 25.1
      mL/h versus 205.7 +/- 55.4 mL/h), CAZ clearance per kg (40.9 +/- 6.1 mL/h/kg
      versus 60.8 +/- 8.3 mL/h/kg), and the GFR expressed in mL/min (3.14 +/- 0.43
      versus 4.73 +/- 0.89) were significantly (p < 0.001) decreased in the asphyxiated
      newborn. We conclude that twice daily administration of 50 mg/kg of body weight
      CAZ given to asphyxiated term newborns in the first days of life results in
      significantly higher serum trough levels in comparison with control infants. The
      impaired CAZ clearance is a result of a significantly decreased GFR.

PMID- 8552454
TI  - Genetic markers on chromosome 19p and prenatal diagnosis of HLA class II
      deficient combined immunodeficiency.
AB  - HLA class II-deficient combined immunodeficiency (CID) is an inherited disease
      characterized by a total lack of HLA class II gene expression, due to a
      regulatory defect affecting these genes. In the family investigated the disease
      phenotype occurs parallel to an abnormal structural feature of the CD23 antigen.
      We sequenced parts of the FCER2 gene coding for CD23 and found a restriction
      fragment length polymorphism (RFLP) that cosegregates with the disease. Analysis
      of recombinant haplotypes by microsatellites mapping to the chromosomal region
      19p13.3 suggests that the disease locus maps between FCER2 and the microsatellite
      marker D19S424, probably close to D19S216 and D19S177. These data may offer the
      possibility of a rapid and early prenatal diagnosis of a subgroup of patients
      with HLA class II-deficient CID.

PMID- 8552455
TI  - The effect of curvature on visual interpolation.
AB  - The effect of curvature on visual interpolation in partly occluded figures was
      examined. In experiments 1 and 2, the shape of a visually interpolated contour
      was measured by using a partially occluded triangle or a partially occluded
      circle as the target figure. The targets were cut off at both sides, with varying
      width from trial to trial. In experiment 1, the peak height, which was supposed
      to represent the shape of the interpolated contour, was measured for each target
      for each size of the visible part. A significant effect of curvature, as the
      difference in the peak height between the targets, was found when the width of
      the visible part was 10 to 20 min. The effect became stronger linearly with
      increasing length of the visible contour (the buildup effect). The effective
      curvature thus appeared to be measured along the visible contour in terms of the
      change of orientation. In experiment 2, the scale invariance of the buildup
      effect was examined with varying observation distance. It was found that the
      effect remained the same across scale if the effect was described in terms of
      visual angle of the visible arc, but not in terms of the proportion of the
      visible part to the whole figure. This suggests that the effect is derived from
      the visible contour, but not from the likelihood of the estimated shape of the
      partly occluded figure. It has been concluded that the curvature induces curved
      interpolation and that the curvature of the visible contour is measured along the
      contour as the change of orientation.

PMID- 8552456
TI  - Amodal completion and vernier acuity: evidence of 'top-but-not-very-far-down'
      processes?
AB  - Vernier thresholds were measured by means of a forced-choice paradigm for
      physically separated bars that were perceived either as separate or as amodally
      completed behind an occluder. The finding that thresholds were not reduced
      (improved) with amodal completion argues against an early neural code for amodal
      completion that is equivalent to physical completion of the vernier bars (ie
      neural propagation/interpolation) and limits the stage at which amodal
      representations could arise via bottom-up processes to neural sites located
      centrally with respect to those involved in position coding. An alternative
      explanation is also considered, that this result reflects the activity of top
      down processes that mediate amodal completion by imposing grouping/organizational
      constraints upon earlier representations of position. In support of this
      proposition it was found that when tested by means of a non-forced-choice
      paradigm without feedback, observers demonstrated a reduced tendency to report
      the presence of a vernier offset when the bars were perceived as amodally
      completed (ie a shift in response bias occurred). This separability of vernier
      acuity and response bias suggests the existence of 'top-but-not-very-far-down'
      grouping processes whose influence does not extend to early representations of
      relative position.

PMID- 8552457
TI  - Production and interpretation of pictures of houses by blind people.
AB  - Subjects were exposed to a three-dimensional model of a house and were asked to
      draw it using a raised-line drawing kit. Independent groups of ten each of
      sighted controls, early-blind, and late-blind subjects were told to identify the
      vantage point of tangible pictures of the model, including side views, 'bird's
      eye' views from above, and views involving linear perspective. The ease or
      difficulty of picture interpretation depended upon the nature of the tangible
      drawing, with much better performance being recorded for side views. Performance
      was poor for foreshortened 3/4 views. Early-blind subjects were particularly
      unlikely to recognize views from above. In a control experiment with blindfolded
      sighted subjects the influence of prior information was examined: some subjects
      were told that the drawings could consist of side view or bird's-eye, top view,
      or 3/4 view drawings. This experiment showed that performance can be greatly
      improved through prior information about the nature of the tangible pictures.

PMID- 8552458
TI  - Factors influencing the accuracy of age estimates of unfamiliar faces.
AB  - Factors affecting the accuracy with which adults could assess the age of
      unfamiliar male faces aged between 5 and 70 years were examined. In the first
      experiment twenty-five 'young' adult subjects, aged 16-25, and twenty-five 'old'
      adults, aged 51-60, were used. Each subject saw five versions of three different
      faces: these consisted of an original version of each face and four manipulated
      versions of it. The manipulations consisted of mirror reversal, pseudo-cardioidal
      strain, thresholding, and elimination of all but the internal features of the
      face. The second experiment was similar except that a between-subjects design was
      used: each subject saw three faces for each age category of target face, but was
      exposed to only a single type of manipulation (plus a set of 'original' faces
      which were identical for all groups, so that the comparability of the different
      groups in age estimation could be checked). Results from both experiments were
      similar. Age estimates for unmanipulated 'original' faces were highly accurate,
      although subjects were most accurate with target faces that were within their own
      age range. Results for the manipulated faces implied that the importance of
      cardioidal strain as a necessary and sufficient cue to age may have been
      overestimated in previous reports: subjects' age estimates were accurate when
      cardioidal strain was absent from the stimulus, and poor when cardioidal strain
      was the only cue available.

PMID- 8552459
TI  - Is the richness of our visual world an illusion? Transsaccadic memory for complex
      scenes.
AB  - Our construction of a stable visual world, despite the presence of saccades, is
      discussed. A computer-graphics method was used to explore transsaccadic memory
      for complex images. Images of real-life scenes were presented under four
      conditions: they stayed still or moved in an unpredictable direction (forcing an
      eye movement), while simultaneously changing or staying the same. Changes were
      the appearance, disappearance, or rotation of an object in the scene. Subjects
      detected the changes easily when the image did not move but when it moved their
      performance fell to chance. A grey-out period was introduced to mimic that which
      occurs during a saccade. This also reduced performance but not to chance levels.
      These results reveal the poverty of transsaccadic memory for real-life complex
      scenes. They are discussed with respect to Dennett's view that much less
      information is available in vision than our subjective impression leads us to
      believe. Our stable visual world may be constructed out of a brief retinal image
      and a very sketchy, higher-level representation along with a pop-out mechanism to
      redirect attention. The richness of our visual world is, to this extent, an
      illusion.

PMID- 8552461
TI  - Why isn't sociology a science?

PMID- 8552460
TI  - Temporal competition between odorants: effect of different time intervals on the
      perception of monorhinic and dichorhinic binary mixtures.
AB  - Backward masking and its possible connection with the perception of odour
      mixtures has been investigated. Temporal competition between odorants in a binary
      mixture was tested by artificially creating a delay between one odour (the
      target) and a second, stronger, odour (the mask) during a single natural sniff.
      To test the influence of central versus peripheral competition, the same mixture
      was presented either monorhinically or dichorhinically. The delay (100 to 400 ms)
      did not influence intensity perception, indicating that intensities are
      integrated during the sniff irrespective of the temporal arrangement. In
      contrast, the number of qualities perceived was influenced by the delay: delays
      of 200 to 400 ms gave significant increases in the frequency of detection of a
      mixture, whereas synchronous mixtures favoured the perception of a single odour.
      Masking was also significantly stronger in dichorhinic mixtures. These effects
      are discussed in terms of retroactive masking which seems to be enhanced by
      dichorhinic mixtures, suggesting that masking has an important central component.

PMID- 8552462
TI  - The perceptual flattening of three-dimensional scenes enclosed by a frame.
AB  - The effects of a visible frame around a three-dimensional scene on perceived
      depth within the scene was investigated in three experiments. In experiment 1
      subjects judged the slant of an object that had been rotated about a vertical
      axis. Judged slant was reduced when the frame was illuminated. In experiments 2
      and 3 subjects judged the shape (width-to-height ratio) of the object. The object
      was judged to be narrower when the frame was illuminated (experiment 2) or when a
      frame was added to the scene in an illuminated room (experiment 3). These results
      demonstrate that the presence of a frame around a three-dimensional scene serves
      as a flatness cue, reducing perceived depth within the scene.

PMID- 8552463
TI  - What hinders accurate depiction of projective shape?
AB  - Adult subjects drew the visual projection of two models. One model was a
      trapezoid placed in the frontoparallel plane. The other was a tilted rectangle
      which displayed the same projective shape on a frontoparallel plane as the
      trapezoid. The drawing conditions were varied in two ways: the model remained
      available for inspection during the drawing task or it was masked after initial
      inspection; the subjects drew on paper placed flat on the table or on a vertical
      glass pane placed in front of the model (ie on a da Vinci window). The results
      were that (i) the projective shape of the frontoparallel trapezoid was reproduced
      accurately whereas that of the tilted rectangle was systemically distorted in the
      direction of its actual physical dimensions; (ii) when subjects drew on paper,
      the presence or absence of a view of the model made no difference to the amount
      of distortion; (iii) drawing on a da Vinci window improved accuracy even when the
      model was hidden. These findings provide information about the relative roles of
      object-centred knowledge, perceptual abilities, and depiction skills in drawing
      performance.

PMID- 8552464
TI  - Families' perspectives of clozapine treatment.
AB  - PROBLEM: How do family members perceive their loved one's clozapine treatment and
      what recommendations do they put forth for other families, clients, and health
      professionals. METHODS: An exploratory descriptive design was used. A convenience
      sample of 10 families from the "Alliance for the Mentally Ill" responded in an
      audiotaped personal interview to eight items on an interview guide. Data were
      analyzed by the double-coding qualitative method. FINDINGS: Family members have
      specific concerns about their loved one's clozapine treatment. CONCLUSION:
      Forming an alliance with family members of clients receiving clozapine will
      encourage optimal treatment effectiveness.

PMID- 8552465
TI  - The therapeutic use of dolls.
AB  - TOPIC: Using dolls as therapy in a psychogeriatric unit. PURPOSE: To acquaint
      nurses with this therapeutic modality. SOURCE: The Dolls Project. CONCLUSION:
      Dolls can be used therapeutically to awaken pleasurable affective responses in
      the older psychiatric client.

PMID- 8552466
TI  - The bruises that don't show.

PMID- 8552467
TI  - Postscript: on carrying and being carried.

PMID- 8552469
TI  - The PPC nurse-therapists directory.

PMID- 8552468
TI  - The degrading of America: violence toward women.

PMID- 8552470
TI  - Healing the wounds of war: the Vietnam veteran after Operation Desert Storm.
AB  - TOPIC: How Operation Desert Storm, and the positive response of the public to
      this crisis, seemed to stimulate and heighten unresolved feelings for many
      Vietnam veterans. PURPOSE: To show that understanding the lived experiences of
      Vietnam veterans, at time when men and women returning from Operation Desert
      Storm were welcomed back by their country, would allow for the development of
      more effective treatment approaches in working with Vietnam veterans. METHODS:
      Personal interviews, during and immediately following Operation Desert Storm,
      with 12 men who served in Vietnam. FINDINGS: Themes identified and described by
      Vietnam veterans included repressed fear, shame, isolation and loneliness,
      disillusionment, permanence of memories, and acceptance. CONCLUSION: Further
      exploration and analysis of these themes is recommended.

PMID- 8552471
TI  - Understanding the rapist's mind.
AB  - TOPIC: The motivations and psychology of the rapist. PURPOSE: To provide a
      framework of sexual perversions so that the motives and psychology of rapists can
      be better understood. SOURCE: Analytic literature. CONCLUSION: Unconscious
      motives leading to rape appear related to issues of control, power, and
      dominance.

PMID- 8552472
TI  - Nursing: the career of a lifetime.

PMID- 8552473
TI  - Professional development. Trauma: revision notes [continuing education credit].

PMID- 8552474
TI  - Unequal treatment. Interview by David Payne.

PMID- 8552475
TI  - Cry pay rise.

PMID- 8552476
TI  - Fractured service.

PMID- 8552477
TI  - Mixing company.

PMID- 8552478
TI  - Moving closer.

PMID- 8552479
TI  - The nursing management of dyspnoea in palliative care.

PMID- 8552480
TI  - Support for carers of people with learning disabilities.
AB  - The current rhetoric associated with the provision of community care might lead
      some to conclude that services for people with a learning disability and their
      families has improved significantly. However, a recent interview with a mother
      who has a young son with a profound learning disability and associated
      behavioural problems, questions such assumptions.

PMID- 8552481
TI  - What do nurses want from social workers?
AB  - This study is based on a series of interviews with 45 senior nurses and outlines
      their perceptions about, and expectations of, social workers. The study found
      that nurses want social workers to provide a range of practical services for
      patients and to act as a bridge with the community, making use of their unique
      position to move between health and social services. They want a mutually
      satisfying professional working relationship with social workers based on trust,
      confidence and reliability. And they want them to fulfill their statutory
      responsibilities with expertise.

PMID- 8552482
TI  - Resuscitation decisions--when should we talk to patients?
AB  - This paper attempts to summarise the results of recent British studies in the
      area of resuscitation decisions, and to explain the ethical and legal framework
      for the use of 'do not resuscitate' decisions and to give clear guidance about
      involving patients and relatives.

PMID- 8552483
TI  - No time for kid gloves.

PMID- 8552484
TI  - A creditable experience.

PMID- 8552485
TI  - Mind the gap.

PMID- 8552486
TI  - Infection control. When winter makes you sick.

PMID- 8552487
TI  - Infection control. Personal contacts.

PMID- 8552488
TI  - Call for HIV therapy cash.

PMID- 8552489
TI  - Professional development. Digestive tract cancers: knowledge for practice
      (continuing education credit).

PMID- 8552490
TI  - How nurses cope with exposure to HIV infections.

PMID- 8552491
TI  - On the rocks.

PMID- 8552492
TI  - Catalyst for courage. Interview by David Payne.

PMID- 8552493
TI  - Plagued by prejudice.

PMID- 8552494
TI  - No way out.

PMID- 8552495
TI  - Human rights. Right to fight.

PMID- 8552496
TI  - Human rights. Everybody's business.

PMID- 8552497
TI  - The screening imperative for ophthalmic care in diabetes.
AB  - In the light of the prevalence of diabetes mellitus there is a need for its
      inclusion in future health targeting and also for a national screening programme
      to detect diabetic eye disease. Screening will enable early treatment, contribute
      to reduced demands on resources and influence positively the lowering of the
      incidence of new blindness.

PMID- 8552498
TI  - The levels of pain experienced with lower limb fractures.
AB  - This paper gives an overview of a small study of practice in Coventry and
      Warwickshire Hospital. The study set out to discover how long male patients
      experienced unrelieved pain following admission to hospital with fractures to
      their lower limbs.

PMID- 8552499
TI  - The management of childhood asthma through care pathways.
AB  - The incidence of childhood asthma is on the increase with mounting pressure on
      health professionals caring for these children. Any attempt to develop services
      for children with asthma must address the problem of coordinating care between
      hospitals, GPs and community nurses, and should include the issue of parental
      involvement. This paper describes how a care pathway is used as a tool to promote
      partnerships of care between hospital, community and the family, and to
      coordinate the service.

PMID- 8552500
TI  - A comparison of factor VIII infusion methods.
AB  - This paper describes a case study approach to evaluating practice. It compares
      two different methods of factor VIII infusion for a patient with haemophilia who
      underwent two orthopaedic operations.

PMID- 8552501
TI  - A study of the use of tape-recorded handovers.
AB  - The handover of information between shifts is often a time-consuming activity. It
      can involve all available staff from both shifts being absent from the ward for a
      substantial period of time. At a time when cost-effectiveness is an issue, many
      managers are looking at the value for money that the handover period provides.
      This paper describes an attempt by Trinity Hospic in Clapham actively to examine
      the cost in time and money that handover incurred, together with an examination
      of the quality of staff-to-staff reporting using tape-recorded handovers.

PMID- 8552502
TI  - Diabetes: dietary management.

PMID- 8552503
TI  - Rough justice.

PMID- 8552504
TI  - Services do need specialists.

PMID- 8552505
TI  - Learning disabilities. Marriage of convenience.

PMID- 8552506
TI  - Learning disabilities. Foundation course.

PMID- 8552507
TI  - Learning disabilities. Twice the practitioner.

PMID- 8552508
TI  - Warning on infection risk to patients with HIV.

PMID- 8552509
TI  - Manpower concerns in cardiac electrophysiology and pacing.

PMID- 8552510
TI  - The evolution of platelet aggregability in patients undergoing catheter ablation
      for supraventricular tachycardia with radiofrequency energy: the role of
      antiplatelet therapy.
AB  - Forty-two consecutive patients were checked for profiles of platelet
      aggregability before, during, and 10 and 30 minutes after catheter ablation. They
      were randomized into Group A (n = 20) who accepted intravenous aspirin (in 0.015
      g/kg body weight) and Group P (n = 22) who accepted only placebo treatment. Blood
      samples were drawn from ascending aorta (Ao) and main pulmonary artery (MPA)
      simultaneously at each time period. In Group P, the EC50 of substrate induced
      platelet aggregability decreases significantly during (for ADP, from 1.72 to 0.78
      mumol/L for samples from Ao, P < 0.0001; and from 1.68 to 0.69 mumol/L for MPA, P
      < 0.0001; for collagen, from 2.26 to 1.34 micrograms/mL for Ao, P < 0.005, and
      from 2.40 to 1.64 micrograms/mL, P < 0.0001) and 10 minutes after successful
      ablation (for ADP, to 0.70 mumol/L for Ao, P < 0.000, and to 0.61 mumol/L for
      MPA, P < 0.0001; for collagen, to 1.54 micrograms/mL for Ao, P < 0.01, and to
      1.63 micrograms/mL, P < 0.0001), and then returned to baseline levels 30 minutes
      later (all P = NS) compared with comparative baseline levels. The levels of
      thromboxane B2 (TXB2) had the similar evolution. The evolution of platelet
      aggregability profiles was not associated with total energy dose, duration of
      energy application, duration of procedure, impedance, and ablation site. However,
      there were moderate positive correlations between the TXB2 levels and tip
      temperatures (r = 0.56, P < 0.05 for Ao and r = 0.65, P < 0.01 for MPA). These
      results suggest that increased platelet aggregability can occur during and 10
      minutes after radiofrequency current ablation and antiplatelet therapy can
      maintain "flat" response of platelet aggregability to radiofrequency energy,
      which may provide possible benefits in preventing the occurrence of the
      complication.

PMID- 8552511
TI  - Reproducibility of time and frequency domain analysis of heart rate variability
      in patients with chronic stable angina.
AB  - Before heart rate variability (HRV) can be used to investigate the effects of
      drugs or other clinical interventions in chronic stable angina, it is important
      to establish the stability and reproducibility of HRV indices over time. HRV
      analysis was performed on two consecutive 24-hour ambulatory ECG recordings in 19
      patients with chronic stable angina. Time-domain analysis included average heart
      rate, variance, SDNN, SDANN5, ASDNN5 and PNN50. The power spectral analysis was
      computed using fast Fourier transformation for the total power (0.003 and 0.40
      Hz), low frequency (0.04-0.15 Hz), and high frequency (0.15-0.40 Hz) bands. No
      statistically significant differences in the time or frequency domains were found
      between the two ambulatory ECG recordings. HRV indices in the time and frequency
      domains are consistent and reproducible in patients with chronic stable angina.
      Thus, cardiac autonomic tone can be evaluated using HRV analyses, and any
      significant changes that occur after medical therapy or other clinical
      interventions can be ascribed to the intervention rather than the lability of
      cardiac autonomic tone.

PMID- 8552512
TI  - Bipolar transvenous defibrillation: efficacy of two different positions of the
      anode.
AB  - For most nonthoracotomy defibrillation lead systems, the transvenous anode can
      positioned independently of the right ventricular (RV) cathode. Usually a
      vertical position in the superior vena cava (SVC) is chosen. However, it is
      unknown if this position yields the optimal defibrillation threshold (DFT).
      Therefore, in 15 patients undergoing defibrillator implantation the SVC position
      was compared in a crossover study design with a horizontal position in the left
      brachiocephalic vein (BCV). Mean DFT was not different for SVC and BCV (19.2 +/-
      9.6 J vs 18.5 +/- 9.1 J) but DFT of individual patients differed by up to 12
      joules. A positive correlation between impedance and DFT in the BCV position (r =
      0.6; P < or = 0.05) indicated that the improved geometry of the defibrillation
      field with the BCV position is opposed by a higher impedance found for this
      position (63 +/- 15 omega vs 52 +/- 7 omega). Thus, defibrillation is not
      improved in general although individual patients might benefit.

PMID- 8552513
TI  - Thermistor guided radiofrequency ablation of atrial insertion sites in patients
      with accessory pathways.
AB  - Radiofrequency ablation has gained acceptance in the treatment of patients with
      symptomatic Wolff-Parkinson-White syndrome. The purpose of this study was to
      characterize the relation between temperature and other electroconductive
      parameters in patients undergoing atrial insertion accessory pathway ablation
      utilizing a thermistor equipped catheter. The mean temperature and power at sites
      of atrial insertion ablation are lower than has been previously associated with
      creation of radiofrequency lesions in the ventricle. While high cavitary blood
      flow in the atrium may result in cooling, the thinner atrial tissue may require
      less energy to achieve adequate heating than ventricular myocardium.

PMID- 8552514
TI  - Influence of malpositioned transvenous leads on defibrillation efficacy with and
      without a subcutaneous array electrode.
AB  - Some patients cannot receive a transvenous lead system because of high
      defibrillation thresholds (DFTs). We hypothesized that a right ventricular (RV)
      catheter electrode not extending as far as possible into the RV apex could cause
      high DFTs. Recently, a subcutaneous array (SQA) electrode has been shown to lower
      DFTs substantially. We compared the influence of a malpositioned RV catheter
      electrode on defibrillation efficacy for endocardial lead systems with and
      without a SQA. In eight anesthetized pigs, defibrillation catheters were placed
      in the RV apex and near the junction of the superior vena cava (SVC) and right
      atrium. SQA, formed by three elements, each 20 cm in length, was placed in the
      left thorax. DFTs were determined for a biphasic waveform using an up/down
      protocol with the RV catheter at the apex and with it repositioned 1-cm and 2-cm
      proximal to the apex. The mean DFT energies for the configurations with a SQA
      were less than those without a SQA for every catheter position. The placement of
      the RV catheter away from the apex caused an increase in defibrillation energy
      for the configurations without a SQA (apex: 17.1 +/- 3.8 J [mean +/- SD]; 1 cm:
      20.1 +/- 4.6 J; 2 cm: 27.6 +/- 9.5 J; P < 0.05), but not for the configurations
      with a SQA (apex: 12.2 +/- 2.2 J; 1 cm: 12.3 +/- 2.9 J; 2 cm: 12.1 +/- 0.9 J: P =
      NS). These results suggest that a malpositioned RV catheter electrode, at the
      time of implantation or by late dislodgment, significantly elevates DFTs for a
      total endocardial system but not for a system that includes a SQA.

PMID- 8552515
TI  - Estimation of temperature during radiofrequency catheter ablation using impedance
      measurements.
AB  - Temperature monitoring during radiofrequency catheter ablation is useful but
      requires specialized equipment that is not generally available. Previous studies
      have shown that impedance characteristically decreases as the result of heating
      at the electrode-tissue interface. The purpose of the current study was to
      determine if impedance changes during radiofrequency current application could be
      used to estimate endocardial temperature in patients undergoing catheter
      ablation. Data from 43 patients treated with a thermistor ablation catheter were
      retrospectively analyzed. The slope of the initial 2 seconds of the impedance
      curve and subsequent changes in impedance were incorporated into an equation for
      estimation of temperature in real-time. The accuracy of this equation was
      assessed by prospectively comparing the calculated and measured temperatures in
      19 patients. Of the 88% of energy applications that were suitable for analysis,
      the average difference between calculated and measured temperatures was 5.2 +/-
      5.6 degrees C. The average error was < 10 degrees C in 89% of applications. The
      results of this study suggest that impedance measurements can be used to quantify
      tissue temperature in real-time during radiofrequency catheter ablation. This
      method is sufficiently accurate to allow titration of power output to produce
      temperatures in the useful range (50-80 degrees C) while avoiding excessive
      heating (> 90 degrees C).

PMID- 8552516
TI  - Electrophysiological effects of MS-551 in humans: a class III antiarrhythmic
      agent.
AB  - To investigate the clinical effects of MS-551, a Class III antiarrhythmic agent,
      11 patients underwent electrophysiological study. MS-551 was given intravenously
      as an initial dose of 0.2 or 0.3 mg/kg for 5 minutes followed by the continuous
      infusion at 0.2 or 0.3 mg/kg for 30 minutes, respectively, in all patients. The
      rate corrected QT interval increased significantly from 3 minutes after the
      beginning of MS-551 infusion. The sinus heart rate decreased significantly by 8%
      at 10 minutes after the drug administration (P < 0.025). Mean PR and QRS
      intervals, and blood pressure were not significantly affected by the drug. Mean
      PA, AH, and HV intervals during sinus rhythm were also not affected. The
      effective refractory periods (ERPs) of the atrium and ventricle were
      significantly prolonged by 13% from 202 +/- 24 ms to 231 +/- 26 ms (P < 0.0005),
      and by 7% from 238 +/- 11 ms to 257 +/- 13 ms (P < 0.002), respectively, by MS
      551. The ERP of the atrioventricular node and sinoatrial nodal recovery time were
      not changed significantly by the drug. This is a report of the effects of MS-551
      in humans. This agent could be useful for treatment of tachyarrhythmias by
      prolongation of ERPs of the atrium and ventricle without significant variations
      of blood pressure and intracardiac conduction times. It is noteworthy that MS-551
      slightly but significantly decreased heart rate.

PMID- 8552517
TI  - Adverse pacemaker hemodynamics evaluated by pulmonary venous flow monitoring.
AB  - The pacemaker syndrome refers to symptoms and signs in the pacemaker patient
      caused by an inadequate timing of atrial and ventricular contractions. The lack
      of normal atrioventricular synchrony may result in a decreased cardiac output and
      venous cannon A waves. The objective of this study was to define the left atrial
      and pulmonary venous flow response to ventricular pacing in a group of 14
      unselected consecutive patients with total heart block and sinus rhythm.
      Pulmonary venous flow was assessed by transesophageal pulsed Doppler
      echocardiography in the VVI and DDD pacing modes. An inappropriate atrial timing
      caused a marked augmentation of the normally small pulmonary venous z wave in all
      patients ("negative atrial kick," peak z wave in DDD pacing 14.5 +/- 4.6 cm/s,
      VVI pacing 51.8 +/- 15.0 cm/s). Restoration of AV synchrony (DDD pacing, AV
      interval 100 ms) abolished these "cannon z waves" in all patients, and a normal
      pattern of pulmonary venous flow was achieved. Abnormal pulmonary venous flow
      characteristics were observed in 2 of 14 patients during DDD pacing with short AV
      intervals (100 ms). The Doppler pattern was similar to the findings seen in VVI
      pacing. Assessment of pulmonary venous flow by transesophageal pulsed Doppler
      echocardiography may provide a simple, sensitive, and relatively noninvasive
      technique to evaluate patients with suspected pacing induced adverse
      hemodynamics.

PMID- 8552518
TI  - Efficacy of antitachycardia pacing in patients presenting with cardiac arrest.
AB  - The efficacy of antitachycardia pacing (ATP) incorporated into implantable
      cardioverter defibrillators (ICDs) was assessed in 29 consecutive survivors of
      cardiac arrest, not attributable to acute myocardial infarction, ischemia, or
      drug and electrolyte effects. The cohort included 25 men and 4 women with a mean
      age of 65 years and a mean left ventricular ejection fraction of 29%. Seventeen
      patients had coronary artery disease, 11 had nonischemic dilated cardiomyopathy,
      and 1 had long QT syndrome. Programmed stimulation yielded monomorphic
      ventricular tachycardia (VT) in 17 patients, polymorphic VT in 6, and no
      inducible VT in 6. During a mean follow-up of 22 months, a total of 91 episodes
      of monomorphic VT occurred, 73 of which were successfully pace terminated (83%).
      Monomorphic VT amenable to pace termination recurred only in the group that had
      this arrhythmia inducible. The recurrent arrhythmias in the 12 patients having
      either no inducible VT or polymorphic VT were all rapid VTs, having a cycle
      length < 220 ms; and therefore, not amenable to pace termination. These results
      suggest that ATP incorporated into ICDs is useful in survivors of cardiac arrest
      and may significantly reduce the number of shocks that these patients would
      otherwise receive. Programmed stimulation may also help to define those patients
      who would receive the maximum benefit from ATP.

PMID- 8552519
TI  - Use of double ventricular extrastimulation to determine the preexcitation index
      in atrioventricular nodal reentrant tachycardia.
AB  - The ability of single paced ventricular beats during tachycardia to penetrate the
      tachycardia circuit and reset the subsequent atrial depolarization (atrial
      preexcitation), enabling calculation of the "preexcitation index," can be helpful
      in analyzing supraventricular tachycardias. However, the ventricular refractory
      period often prevents ventricular capture of beats with the necessary prematurity
      to demonstrate atrial preexcitation, particularly in atrioventricular nodal
      reentrant tachycardia (AVNRT). We hypothesized that the use of double premature
      stimuli could overcome this limitation. In 25 consecutive patients with either
      AVNRT or atrioventricular reciprocating tachycardia (AVRT) we attempted to
      demonstrate atrial preexcitation with single and double ventricular extrastimuli.
      Whereas atrial preexcitation with a single extrastimulus could only be achieved
      in 3 of 11 patients with AVNRT, all but 1 patient demonstrated atrial
      preexcitation with the use of double ventricular extrastimuli. On the other hand,
      in all but 1 patient with AVRT, atrial preexcitation could be achieved with
      single and double extrastimuli. A formula was derived for obtaining a
      preexcitation index with double extrastimuli and shown to correspond closely with
      the preexcitation index obtained with a single extrastimulus in the 16 patients
      in whom atrial preexcitation could be achieved with single and double
      extrastimuli. Thus, this technique significantly enhances the ability to achieve
      atrial preexcitation and to calculate the preexcitation index in patients with
      AVNRT, and thus may be useful in deciphering tachycardia mechanism in some
      patients, as well as being a useful technique in studying the
      electrophysiological properties of the antegrade and retrograde limbs of AVNRT.

PMID- 8552520
TI  - Incidence of ICD lead related complications during long-term follow-up:
      comparison of epicardial and endocardial electrode systems.
AB  - The aim of this study was to evaluate the long-term stability of epicardial and
      endocardial lead systems for third-generation cardioverter defibrillators (ICDs)
      and to assess the usefulness of diagnostic tools. One hundred forty patients with
      61 epicardial (43.6%) and 79 nonthoracotomy systems (56.4%) were followed for 25
      +/- 19 months. A total of 18 (12.9%) lead related complications were documented.
      Complications of epicardial systems were detected in 10 patients (16.4%) during a
      follow-up time of 36 +/- 8 months: crinkling of patch electrodes in 6 patients
      (9.8%), insulation breakage of sensing electrodes in 2 patients (3.3%), and
      adapter defect in 2 patients (3.3%). Eight of the patients (10.1%) with
      transvenous-subcutaneous systems had lead related complications during a 13 +/- 6
      months follow-up: fracture of the subcutaneous patch lead in 2 patients (2.5%),
      dislodgement of the right ventricular lead in 2 patients (2.5%), dislodgement of
      the superior vena cava lead in 2 patients (2.5%), insulation breakage of sensing
      electrodes in 1 patient (1.3%), and connector defect in 1 patient (1.3%). There
      was no significant difference in the incidence of lead related complications
      between epicardial and endocardial systems (P > 0.05). Fractures, dislodgements,
      and crinklings were documented within the first 8 +/- 5 months by regular chest X
      ray. Defects of insulation, adapter, or connector were detected 22 +/- 10 months
      after implantation and were associated with delivery of multiple inappropriate
      ICD therapies. An operative lead revision was indicated for 4 epicardial (6.6%)
      and 6 endocardial (7.6%) lead systems. CONCLUSIONS: Endocardial lead systems
      offer a similar long-term stability as compared to epicardial lead systems. Chest
      X ray is the most useful tool to detect lead fracture, dislodgment, and patch
      crinkling. Marker recordings or real-time electrograms have not been helpful in
      this series to identify patients with suspected lead defects prior to the
      experience of inappropriate ICD discharges.

PMID- 8552521
TI  - Anatomical findings in patients having had a chronically indwelling coronary
      sinus defibrillation lead.
AB  - The purpose of this report is to review the gross and histological cardiac
      anatomical findings in patients with chronically indwelling coronary sinus leads
      at the time of autopsy or cardiac transplantation. Transvenous cardioverter
      defibrillators offer effective protection against sudden death. The use of a
      coronary sinus electrode has been shown in some patients to decrease the
      defibrillation threshold. The anatomical consequences of chronically indwelling
      coronary sinus cardioversion/defibrillation electrodes in patients having
      transvenous implantable cardioverter defibrillators is unknown. The hearts of
      seven patients with chronically indwelling coronary sinus electrodes were
      evaluated following autopsy (n = 2) or cardiac transplantation (n = 5). The
      coronary sinus electrode in each case was a 6.5 French silicone lead with a 5-cm
      long defibrillation coil (Medtronic CS lead model 6933) that was positioned as
      distally as possible within the coronary sinus at the time of implantable
      cardioverter defibrillator surgery. The seven hearts examined were derived from
      patients whose age ranged between 49 and 69 (mean 56 +/- 7 years). Six had
      coronary artery disease and one had idiopathic dilated cardiomyopathy. The time
      from implant to death or cardiac transplantation was 8 +/- 6 months, range 1-18
      months. In all seven patients, there was no evidence of any significant damage
      from the presence of the coronary sinus lead. The only finding in each case was
      the scattered presence of a thin white fibrous sheath over the lead that
      intermittently adhered to the coronary sinus endothelium and, in the two patients
      transplanted 1-3 months after implantable cardioverter defibrillator insertion, a
      mild inflammation reaction adjacent to the leads in the coronary sinus
      endothelium. There was no evidence of coronary sinus occlusion, adjacent coronary
      artery injury, coronary sinus perforation, coronary sinus burn, or myocardial
      injury adjacent to the lead. Cause of death was due to end-stage congestive heart
      failure and thrombotic stroke, respectively, in the two patients examined at
      autopsy. Coronary sinus defibrillation leads can be used safely without harmful
      anatomical effect.

PMID- 8552522
TI  - Impedance to defibrillation countershock: does an optimal impedance exist?
AB  - Defibrillation is thought to occur because of changes in the transmembrane
      potential that are caused by current flow through the heart tissue. Impedance to
      electric countershock is an important parameter because it is determined by the
      magnitude and distribution of the current that flows for a specific shock
      voltage. The impedance is comprised of resistive contributions from: (1) extra
      tissue sources, which include the defibrillator, leads, and electrodes; (2)
      tissue sources, which include intracardiac and extra-cardiac tissue; and (3) the
      interface between electrode and tissue. Tissue sources dominate the impedance and
      probably contribute to the wide range of impedance values presented to the
      defibrillation pulse. Because impedance is not constant within or between
      subjects, defibrillators must be designed to accommodate these differences
      without compromising patient safety or therapeutic efficacy. Experimental
      investigations in animals and humans suggest that impedance changes at several
      different time scales ranging from milliseconds to years. These alterations are
      believed to be a result of both electrochemical and physiological mechanisms. It
      is commonly thought that impedance is optimized when it has been decreased to a
      minimum, since this allows the most current flow for a given voltage shock.
      However, if the impedance is lowered by changing the location or size of the
      electrodes in such a way that current flow is decreased in part of the heart even
      though current flow is increased elsewhere, then the total voltage, current, and
      energy needed for defibrillation may increase, not decrease, even though
      impedance is decreased. A simple boundary element computer model suggests that
      the most even distribution of current flow through the heart is achieved for
      those electrode locations in which the impedance across the heart is at or near
      the maximum cardiac impedance for any location of these particular electrodes.
      Thus, the optimum shock impedance is achieved when impedance is minimized for
      extra-tissue and extra-cardiac tissue sources and is at or near a maximum for
      intracardiac tissue sources.

PMID- 8552523
TI  - Three cardiology journals on CD-ROM.

PMID- 8552524
TI  - Enough already? The training of new EP and pacing physicians.

PMID- 8552525
TI  - Incessant ventricular tachycardia associated with congestive heart failure.

PMID- 8552526
TI  - Instantaneous lead entrapment: an unusual complication of nonthoracotomy
      implantation of an endocardial defibrillation lead.
AB  - Nonthoracotomy implantation of implantable cardioverter defibrillators is
      performed with transvenous leads that are similar to pacemaker leads and are
      subject to the same potential problems. We report an unusual complication of lead
      placement in which an electrode immediately became entrapped in the superior rim
      of the tricuspid valve, resisting all efforts at removal.

PMID- 8552527
TI  - Successful long-term ventricular pacing via the coronary sinus after the Fontan
      operation.
AB  - A man with double inlet left ventricle and severe subpulmonary stenosis underwent
      a Fontan operation at the age of 29 years. Eight years later he developed atrial
      flutter with complete heart block. To avoid a further thoracotomy, a unipolar
      carbon tipped electrode was placed into the posterior cardiac vein via the
      coronary sinus. More than 8 years after implantation of the original lead, and
      after two generator changes, telemetric thresholds remain between 1.8-2.1 volts.
      Percutaneous transvenous ventricular pacing via the coronary sinus can produce an
      excellent long-term result and should be the initial approach of choice after a
      Fontan-type operation.

PMID- 8552528
TI  - Wide complex tachycardia due to automaticity in an accessory pathway.
AB  - Patients with the Wolff-Parkinson-White (WPW) syndrome have preexcited
      tachycardia as the result of atrial arrhythmias or antidromic reentry. This
      article describes a patient with persistent wide complex tachycardia due to
      abnormal automaticity in the accessory pathway. Radiofrequency catheter ablation
      resulted in simultaneous elimination of accessory pathway conduction and
      automaticity. Accessory pathway automaticity may be an infrequent cause of
      preexcited tachycardia in patients with the WPW syndrome.

PMID- 8552529
TI  - The cost of the illness that defies.

PMID- 8552530
TI  - A virus view of the human condition.

PMID- 8552531
TI  - A bacterial pathogen's view of the human condition.

PMID- 8552532
TI  - Anorexia nervosa--diagnosis, aetiology, and treatment.
AB  - The aetiology, assessment and treatment of anorexia nervosa are reviewed in the
      light of the classical accounts of Morton, Lasegue and Gull. The core symptoms
      are deliberate weight loss, disturbed body image and amenorrhoea, and
      complications may include cardiac failure, electrolyte disturbances, hypothermia
      and osteoporosis. Common clinical findings are described. Disturbed brain
      serotonin activity is implicated in the aetiology of anorexia nervosa, but there
      is little support for the use of pharmacological treatments. Psychological
      theories of aetiology are discussed with reference to Bruch, Crisp, Palazzoli and
      Minuchin: the common theme is the reaction of the patient and her family to the
      physical and social changes of puberty. Individual and/or family psychotherapy is
      seen as central to the treatment of anorexia nervosa, and the relevant clinical
      research is reviewed. The roles of general practitioners, general psychiatrists
      and eating disorder specialists are discussed in the light of recent consensus
      treatment guidelines.

PMID- 8552533
TI  - Martorell's ulcer.
AB  - This paper reports a rare form of ulceration of the lower leg and, as a result of
      subsequent investigations and literature review, readdresses a recent debate
      regarding the legitimate classification of these ulcers as a separate disease
      entity.

PMID- 8552534
TI  - The investigation of a patient with unexpected venous thrombosis.
AB  - Over recent years a number of hereditary and acquired defects of the
      circulation's natural anticoagulant mechanisms have been characterised and shown
      to predispose affected individuals to thrombosis. It is important to attempt to
      diagnose a thrombophilia state in patients with a thrombotic tendency in order to
      provide appropriate management, especially during at-risk situations, both for
      themselves and asymptomatic relatives identified through family studies. This
      review defines the patients who should be investigated for an underlying
      thrombophilia state and describes the hereditary and acquired disorders which
      should be screened for within an investigation profile. The recently identified
      factor V Leiden mutation which appears to be the most common hereditary cause of
      a thrombotic tendency is described in detail and descriptions of the more
      established thrombophilia states are included. Although the factor V Leiden
      mutation accounts for a significant proportion of cases fulfilling the criteria
      for thrombophilia screening, a predisposing cause for thrombosis remains
      unidentifiable in a large number of patients making it likely that over the years
      to come new thrombophilia states will continue to be identified.

PMID- 8552536
TI  - The clinical skills unit.
AB  - Clinical skills units offer exciting and innovative ways of learning about
      clinical skills. Links between theoretical knowledge and clinical practice are
      appropriate for both undergraduate and postgraduate training. Students and
      doctors can practice and acquire technical and examination skills in a
      standardised and protected environment without being concerned about the distress
      such learning may cause real patients. Models and simulators used in skills units
      are being developed to keep pace with demand, with a corresponding increase in
      standards of quality and durability. As undergraduate medical courses respond to
      the demands of modern clinical practice the use of such facilities will increase.
      This paper describes the functions of skills units and provides practical
      examples of educational strategies in use.

PMID- 8552535
TI  - What should I do about my patient's gall stones?
AB  - The problem of benign biliary disease is one that causes significant morbidity
      and social economic strain in the western world. The classical treatment,
      cholecystectomy, has been challenged by various medical and surgical techniques
      in a seemingly random nature. The development of the treatment of gall stone
      disease is reviewed by analysis of published studies over the last 20 years. The
      advantages and disadvantages are discussed as an overview and summary of the
      current management of gall stone disease in the light of our knowledge of its
      malignant potential.

PMID- 8552537
TI  - Developing comprehensive stroke services: an evidence-based approach.
AB  - The recent interest in the development of services for stroke patients reflects
      an increasing optimism about stroke management and the recognition that properly
      organised care can improve outcomes after stroke. A comprehensive stroke service
      should provide early assessment and investigation of stroke disease in both in
      patient and out-patient settings, acute care for stroke in-patients to manage
      their medical and surgical problems, and rehabilitation for patients with
      persisting functional problems. Other components may include out-patient, day
      hospital or domiciliary rehabilitation facilities and continuing care and support
      facilities for patients discharged from hospital. This article discusses the
      evidence to support different components of a comprehensive stroke service and
      emphasises the need for flexible approaches to different local conditions.

PMID- 8552538
TI  - An audit of echocardiograms in acute left ventricular failure.
AB  - All patients with heart failure should have an echocardiogram to establish a
      diagnosis, both to aid treatment as well as for prognostic reasons. An audit of
      100 case notes of patients admitted with acute left ventricular failure over a 12
      month period found that 26 patients had not had an echocardiogram. Of the 74 who
      did have an echocardiogram 68 patients had reduced systolic function (mean
      ejection fraction 42%). Almost all (93%) were commenced on an angiotension
      converting enzyme (ACE) inhibitor. Those who did not receive an ACE inhibitor had
      no contraindications to these drugs. Seventeen patients had a confirmed
      myocardial infarction. Of these, 11 had an echocardiogram and 10 were discharged
      home on an ACE inhibitor. Despite appropriate indications some patients are
      deprived of echocardiography as well as the benefits of ACE inhibitors.

PMID- 8552539
TI  - Cutaneous metastases of lung cancer.
AB  - The reported incidence of skin metastases from lung cancer varies from 2.8-7.5%.
      In the present study 8.7% of patients had skin metastases, with head and neck
      being the most common sites, nodular lesions the most common, and adenocarcinoma
      the most frequent histology. Although most patients develop these lesions during
      the course of a known progressive disease, they may be the presenting
      manifestation of a primary tumour in the lung. The occurrence of skin lesions in
      lung cancer announces an ominous prognosis. The response to chemotherapy is poor,
      possibly due to poor blood supply to the skin; monitoring response to
      chemotherapy, however, is easier when such lesions are present.

PMID- 8552540
TI  - Medullary carcinoma of the thyroid metastatic to breast.
AB  - Medullary carcinoma of the thyroid commonly spreads to the lymphatics and later
      on in the disease process, to distant sites such as lung, liver and bone. Spread
      to the breast is rare (only two previous reported cases) and presents a major
      diagnostic dilemma. We report a case of metastatic medullary carcinoma of the
      thyroid which presented as a primary breast nodule with ipsilateral axillary
      lymphadenopathy. Clearly it was important to distinguish this tumour from a
      breast primary as each are managed differently. Both cytological and radiological
      investigations were inconclusive but excision biopsy was diagnostic.

PMID- 8552541
TI  - Bacterial meningitis after MMR immunisation.
AB  - Two children developed bacterial meningitis within five days of measles-mumps
      rubella (MMR) immunisation. Diagnosis was delayed because symptoms were
      attributed to the vaccine, although both had a raised C-reactive protein. Fever
      or rash within five days of MMR vaccination are unlikely to be due to the vaccine
      and a raised C-reactive protein suggests bacterial infection.

PMID- 8552542
TI  - Neuropathic urinary retention in the absence of neurological signs.
AB  - We present two cases of painless urinary retention secondary to central
      intervertebral disc prolapse. In neither case were there signs or symptoms
      suggesting an underlying neurological insult. Both patients voided spontaneously
      following neurosurgical intervention. The classical features of acute cauda
      equina compression may be absent in patients with central lumbar disc protrusion.
      Painless urinary retention may be the only physical sign.

PMID- 8552543
TI  - Actinomycosis presenting as carcinoma.
AB  - Actinomycosis is rare compared to carcinoma, but the two conditions can present
      with very similar clinical pictures. Two cases of actinomycosis are reported, one
      thoracic and one pelvic-abdominal which presented as carcinoma and proceeded to
      surgery without a histological diagnosis having been established.

PMID- 8552544
TI  - Diagnostic and management problems in a complex case of connective tissue
      disease.
AB  - A 28-year-old Nigerian woman presented with persistent pyrexia, marked pruritus,
      eosinophilia, myalgias, flitting arthralgias, serositis and massive splenomegaly.
      Intensive investigation for an infective or neoplastic aetiology proved negative.
      Empirical treatment for helminthic infections and tuberculosis was unhelpful.
      Although there were no specific clues to suggest an underlying connective tissue
      disease, a trial of steriods and azathioprine was introduced, with no obvious
      response. Her condition deteriorated to a point where it was decided that
      intravenous immunosuppressive therapy was needed and subsequently, her condition
      improved remarkably. This patient illustrates the problems in the diagnosis and
      management of complex disorders, particularly when classical tests for connective
      tissue diseases are absent. Also, we would like to report that marked pruritus
      can be associated with connective tissue disease.

PMID- 8552546
TI  - Shadowy dilemma.

PMID- 8552545
TI  - Massive reversible pulmonary cysts in a patient with AIDS.
AB  - We report the case of a patient with AIDS who presented with bilateral, massive
      pulmonary cystic disease and pneumothorax presumably caused by Pneumocystis
      carinii which responded to treatment with cotrimoxazole. Follow-up with
      sequential chest X-rays and computed tomography scans showed a progressive
      improvement in the lung cysts which had resolved almost completely 11 months
      later. Several theories have been proposed to explain the cavitary lesions in
      this infection. The course observed in our patient suggests that a non
      destructive mechanism was responsible for his lung cysts.

PMID- 8552547
TI  - Agranulocytosis in a drug addict with recurrent Staphylococcus aureus
      septicaemia.

PMID- 8552548
TI  - Intestinal obstruction in an elderly man.

PMID- 8552549
TI  - A seizure and odd behaviour in a 79-year-old man.

PMID- 8552550
TI  - Chronic diarrhoea associated with Septata intestinalis.

PMID- 8552551
TI  - Transient ischaemic attack, infectious meningitis, or neurosarcoidosis?

PMID- 8552552
TI  - Glucose-6-phosphate dehydrogenase deficiency.

PMID- 8552553
TI  - Prevalence of diabetes in elderly patients with pacemakers.

PMID- 8552554
TI  - Gallstone ileus: an old role for abdominal 'hand' scanning.

PMID- 8552555
TI  - Medicines in the mall.

PMID- 8552556
TI  - A frequent attender.

PMID- 8552557
TI  - Successful strategies for preventing osteoporosis.

PMID- 8552558
TI  - Surgery for urinary tract stone disease.

PMID- 8552559
TI  - Demonstrating your consulting skills.

PMID- 8552560
TI  - Identifying the causes of syncope and palpitations.

PMID- 8552561
TI  - Hypertension: targets for treatment.

PMID- 8552562
TI  - A practical guide to thrombolysis.

PMID- 8552563
TI  - Does counselling for angina and hypertension work?

PMID- 8552564
TI  - Options for managing atrial fibrillation.

PMID- 8552565
TI  - [Selection of optimal conditions for synthesis of protein A-laccase conjugates
      and their use in different variants of immunoenzyme analysis].
AB  - A study to determine optimal molar ratios of Protein A to laccase for the
      synthesis of their conjugate by periodate method is presented. No loss of
      enzymatic or immunological activity of the conjugate developed was observed
      during 6 month. The conjugate could be effectively used in various techniques of
      enzyme immunoassay (competitive or sandwich techniques, dot immunoblotting) for
      immunoglobulin G. The detection limits of the assays for immunoglobulins were
      better than 1 ng/ml.

PMID- 8552566
TI  - "Post-Toronto" reflections on the state of academic surgical pathology.

PMID- 8552567
TI  - B-cell lymphoproliferative disorder complicated by a natural killer cell
      lymphoproliferative disorder of granular lymphocytes associated with T-cell gene
      rearrangement: case report and review of the literature.
AB  - We report an unusual case of natural killer cell lymphoproliferative disorder of
      granular lymphocytes associated with a T-cell receptor (TCR)-beta gene
      rearrangement. The patient developed the disorder 1 month after cessation of
      fludarabine therapy for a B-cell lymphoproliferative disorder. The B-cell
      lymphoproliferative disorder was no longer detectable when the natural killer
      cell lymphoproliferative disorder persisted. Review of the literature reveals
      only one reported case of natural killer cell lymphoproliferative disorder of
      granular lymphocytes associated with a TCR-delta gene rearrangement.

PMID- 8552568
TI  - An unclassified cerebral small cell tumor in a patient with human T-cell
      lymphotropic virus type 1-induced primary extranodal lymphoma.
AB  - We describe an autopsy case of a thalamic tumor in a patient with human T-cell
      lymphotropic virus type 1 (HTLV-1)-induced extranodal lymphoma of the skull.
      Neither brain tumors associated with adult T-cell leukemia nor HTLV-1-induced
      extranodal lymphoma of bone have previously been reported. The tumor, which
      resembled an oligodendroglioma or dysembryoplastic neuroepithelial tumor, was
      composed of medium-sized cells with dark, round-to-polygonal nuclei and a
      mucinous matrix that formed pericellular lakes. Tumor cells were immunoreactive
      with S-100 protein and neuron-specific enolase but not with glial fibrillary acid
      protein, synaptophysin, or vimentin. Tumor cells had prominent rough endoplasmic
      reticulum and free ribosomes with short processes, compatible with an
      oligodendroglial or small neuronal nature. Many atypical lymphocytes had
      infiltrated the leptomeningeal space, subependymal zone along the ventricular
      walls, fornices, corpus callosum, and right frontal lobe. Multinucleated or
      bizarre astrocytes and macrophages were found exclusively in the right frontal
      white matter. The coexistence of this unclassified peculiar brain tumor with
      bizarre astrocytosis suggests a cytopathic effect of HTLV-1 on human glioneuronal
      cells.

PMID- 8552569
TI  - Development of extrasalivary gland lymphoma in myoepithelial sialadenitis.
AB  - Myoepithelial sialadenitis of the salivary gland is associated with an increased
      risk of lymphoma, but criteria that predict its development have not been clearly
      defined. We attempted to identify morphologic and immunologic features that
      correlated with the presence of extrasalivary lymphoma in patients with
      myoepithelial sialadenitis. Twenty-five patients (20 women, 5 men; median age, 56
      yr) were studied with clinical follow-up in 22 patients; 19 were followed for 3
      or more yr (median, 8.0 yr overall). Immunostains were done on paraffin sections
      in 28 of 31 specimens (22 of 25 patients) using antibodies to immunoglobulin
      light chains, CD20, CD45RO, CD3, and CD43. Morphologic features studied included
      density of infiltrate, lymphoepithelial lesions, follicle atypia, and pattern of
      monocytoid B-cells. Twenty-four of 25 patients had dense lymphoid infiltrates
      expanding and effacing salivary gland architecture with lymphoepithelial lesions
      and epimyoepithelial islands; all but one of these cases showed monocytoid B
      cells in and around ducts, whereas six also had interconnecting broad strands of
      these cells. One case showed predominantly follicular hyperplasia. Two cases
      contained follicles with large atypical cells. Plasma cells were monotypic in
      four patients (18%) and polytypic in 18 (82%); in 18 of 28 specimens (64%) from
      15 of 22 patients (68%), monocytoid B-cells coexpressed CD20 and CD43. Seven
      patients developed extrasalivary lymphoma, one before and six after the diagnosis
      of myoepithelial sialadenitis (median, 30.5 mo). Monotypic immunoglobulin in
      plasma cells correlated with past or subsequent extrasalivary lymphoma (P <
      0.005); broad strands of monocytoid B-cells correlated with both monotypic plasma
      cells (P < 0.005) and extrasalivary lymphoma (P < 0.02).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8552570
TI  - Simultaneous development of two different B-cell lymphomas in a patient with
      acquired immune deficiency syndrome evidenced by molecular analysis.
AB  - We report a case of a man positive for the human immunodeficiency virus who
      rapidly died of lymphoma with cerebral, lung, and pericardic involvement. After
      autopsy, histopathological study of the different tumor sites showed the same
      morphological feature of immunoblastic lymphoma, with large areas of necrosis. In
      situ hybridization showed monotypic kappa light chain mRNA within lung lymphoma
      cells and monotypic lambda light chain mRNA within cerebral lymphoma cells.
      Polymerase chain reaction analysis showed two different immunoglobulin heavy
      chain gene rearrangements for lung and cerebral lymphoma. Here the simultaneous
      association of two malignant lymphomas derived from different B-cell clones
      indicates that molecular analysis of different tumor sites can distinguish
      between dissemination of the same lymphoma and simultaneous proliferation of
      different malignant B-cell clones.

PMID- 8552571
TI  - An analysis of prognostic features in infiltrating lobular carcinoma of the
      breast.
AB  - To establish prognostically useful pathologic features for infiltrating lobular
      carcinoma, histologic pattern, nuclear Grade 1 or 2, lymphatic invasion, the
      presence and extent of lobular carcinoma in situ, estrogen and progesterone
      receptor status, axillary lymph node status, tumor size, and pathologic stage
      were assessed as prognostic variables in 92 cases of infiltrating lobular
      carcinoma. Clinical follow-up was obtained (mean duration, 5.2 yr), and patients
      were classified as alive with no evidence of disease, alive with disease, or dead
      of disease. Recurrence (alive with disease and dead of disease) was associated
      with axillary lymph node metastases (P = 0.04), tumors measuring > 1.0 cm (P =
      0.008), and pathologic Stage III/IV disease (P = 0.033). Survival (no evidence of
      disease and alive with disease) was associated with Stage I/II disease (P =
      0.003). Statistically insignificant associations with disease recurrence or
      survival follow: infiltrative pattern (classical, alveolar, solid, mixed),
      nuclear grade, lymphatic vessel invasion, presence of lobular carcinoma in situ,
      extent of lobular carcinoma in situ (< 25% or > or = 25%), and hormone receptor
      status. Many of the prognostic features used in ductal carcinoma do not appear to
      be applicable to infiltrating lobular carcinoma. However, tumor size, axillary
      node status, and pathologic stage are prognostically useful in infiltrating
      lobular carcinoma.

PMID- 8552572
TI  - Abnormalities of p53 and p110RB tumor suppressor gene expression in human soft
      tissue tumors: correlations with cell proliferation and tumor grade.
AB  - The authors tested the hypothesis that alterations in tumor suppressor gene
      expression play a role in tumorigenesis of human soft tissue tumors through
      alterations in control of cell proliferation. Using a set of 66 soft tissue
      tumors, including benign tumors and all three grades of sarcomas, expression of
      the p53 and p110RB tumor suppressor gene products were localized using sensitive
      immunocytochemistry techniques. The hypothesis that alterations in tumor
      suppressor gene expression was related to cell proliferation was tested by
      simultaneously demonstrating the expression of the proliferating cell nuclear
      antigen in methacarn-fixed, paraffin-embedded tissue sections of the same tumors.
      Twenty-two of 66 (33%) and 35 of 68 (53%) tumors demonstrated any degree of p53
      overexpression or loss of p110RB, respectively. A strong correlation between
      increasing tumor grade and both p53 overexpression (P = 0.006) and loss of p110RB
      (P = 0.003) was found. Although there was a correlation between increasing
      proliferating cell nuclear antigen index and overexpression of p53 (P = 0.04), no
      correlations were found between cell proliferation indices and loss of p110RB (P
      = 0.19). Finally, there was a significant correlation between the presence of
      immunocytochemically detectable p53 overexpression and detectable p110RB loss (P
      = 0.02). These studies suggest that although alterations in p110RB may play a
      role in soft tissue sarcoma tumorigenesis and be related to p53 dysfunction,
      p110RB may act through mechanisms other than direct loss of cell proliferation
      control.

PMID- 8552573
TI  - Multiparameter digital image analysis of biliary, ampullary, and pancreatic
      adenocarcinomas.
AB  - Periampullary adenocarcinomas arise from pancreatic, biliary, or ampullary ductal
      epithelium. Their origin is difficult or impossible to discern by routine light
      microscopy of cytologic or small biopsy specimens. We used image analysis to
      describe the morphologic features of Feulgen-stained nuclei of biliary and
      ampullary adenocarcinomas and to compare these findings with those of pancreatic
      ductal adenocarcinomas. Surgically resected cases of ampullary adenocarcinoma (n
      = 7) and cholangiocarcinoma (n = 26) were selected on the basis of available
      formalin-fixed, paraffin-embedded tissue and diagnostic clinical data.
      Disaggregated nuclei were stained by the Feulgen reaction and analyzed using a
      digital image processor. Data from 15 morphonuclear parameters were assessed and
      compared with the results from the morphonuclear analysis of 22 pancreatic ductal
      adenocarcinomas. Multivariate analysis with canonical transformation of the data
      defined the ampullary adenocarcinomas and cholangiocarcinomas as occupying
      similar factorial distributions, whereas the pancreatic carcinomas were separate
      and distinct. Monovariate analysis identified seven parameters distinguishing
      pancreatic carcinoma from both ampullary carcinoma and cholangiocarcinoma, with P
      values < or = 0.001 and two others having P values < or = 0.01. Adenocarcinomas
      of ampullary or bile duct origin possess similar morphonuclear features described
      by image analysis. Image analysis provides a mechanism to discriminate
      adenocarcinomas arising from the bile ducts or ampulla from those arising in the
      pancreas.

PMID- 8552574
TI  - Role of Epstein-Barr virus in pleural lymphomagenesis.
AB  - Longstanding inflammation in chronic pyothorax (CP) plays a role in the
      development of pleural lymphoma; therefore, in 1987, the term pyothorax
      associated lymphoma (PAL) was proposed. A recent study showed in the tumor cells
      of a limited number of patients, the presence of the Epstein-Barr virus (EBV)
      genome together with the expression of latent infection genes in the tumor cells
      of PAL. The purpose of the present study is to evaluate an association of EBV
      with PAL in a large number of patients. In addition, the presence of the EBV
      genome was examined in cases with CP without PAL. Histologic, immunohistochemical
      studies, and analyses by polymerase chain reaction (PCR) and in situ
      hybridization method for EBV were performed on 34 PAL and 16 CP collected by
      nationwide study. Median age of the patients in both diseases was approximately
      70 years with a marked preponderance in men. Mean duration of CP in patients with
      CP alone and with CP complicated with PAL was 33 and 37 years, respectively.
      Histologically all PAL were non-Hodgkin's lymphoma, with immunoblastic type being
      the most common. Immunohistochemistry revealed 28 of 34 PAL to be B-cell type.
      Combined PCR, in situ hybridization method, and immunohistochemistry showed that
      the EBV genome was detected in lymphoma cells in 85% of PAL with almost constant
      expression of latent membrane protein-1. The EBV genome was detected by PCR in
      only one of 16 CP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8552575
TI  - Ber-EP4 immunoreactivity in normal skin and cutaneous neoplasms.
AB  - Ber-EP4 is an antibody raised against a cell membrane glycoprotein of, as yet,
      unknown function. In the skin, the ability to distinguish basal cell carcinoma
      from squamous cell carcinoma has been emphasized. Immunoreactivity in apocrine
      and eccrine secretory coil epithelium, Merkel cell carcinoma, and cutaneous mixed
      tumor has been reported. Having observed more widespread staining than previously
      reported, we sought to characterize further Ber-EP4 immunoreactivity by examining
      76 formalin-fixed and paraffin-embedded proliferative epithelial skin lesions, 2
      sections of fetal skin with developing adnexa, and frozen sections of skin from
      Mohs surgery procedures, using hematoxylin and eosin and Ber-EP4 immunostaining.
      In paraffin-embedded skin, matrical and outer sheath epithelium of vellus anagen
      follicles, inferior segment epithelium of vellus telogen follicles, and secretory
      coils of sweat glands stain with Ber-EP4, but anagen terminal follicle epithelium
      and eccrine and apocrine sweat ducts are negative. On frozen section, additional
      staining of eccrine ducts and cells in the outer sheath and matrix of the
      inferior segment of terminal follicles is noted. Basaloid epithelium of
      trichoepitheliomas, follicular induction over dermatofibromas, mammary Paget's
      disease, and selected other neoplasms showing eccrine or apocrine differentiation
      stain with Ber-EP4. These data indicate that in addition to basal cell carcinoma,
      Ber-EP4 staining may be seen in a variety of proliferative epidermal and adnexal
      lesions.

PMID- 8552576
TI  - Rare earth (cerium oxide) pneumoconiosis: analytical scanning electron microscopy
      and literature review.
AB  - Rare earth pneumoconiosis is an uncommonly reported disease caused by the
      inhalation of dust containing lanthanides, also known as rare earth metals, which
      are common industrial materials. The pathologic manifestations and natural
      history of this disorder are incompletely understood. We describe a male patient
      with a 35-year history of optical lens grinding, an occupation associated with
      exposure to cerium oxide, a rare earth metal-containing compound. The patient
      presented with progressive dyspnea and an interstitial pattern on chest X-ray;
      open lung biopsy showed interstitial fibrosis histologically indistinguishable
      from usual interstitial pneumonitis. However, scanning electron microscopy with
      energy-dispersive X-ray analysis demonstrated numerous particulate deposits in
      the lung, of which the majority contained the rare earth metal cerium alone or in
      combination with other elements. Our case is one of the first to describe rare
      earth pneumoconiosis associated with pulmonary fibrosis in the occupational
      setting of optical lens manufacture. Besides reinforcing the contention that rare
      earth metals are potentially harmful, our case suggests that such agents may be
      causally related to the development of pulmonary fibrosis.

PMID- 8552577
TI  - bcl-2 protein expression in the Barrett's metaplasia-dysplasia-carcinoma
      sequence.
AB  - The bcl-2 proto-oncogene encodes a protein that blocks programmed cell death
      (apoptosis). Although bcl-2 has been shown to be involved in the development of
      follicular lymphoma via a chromosomal translocation t(14;18), little is known
      about its function in non-hematolymphoid neoplasms. The bcl-2 protein is normally
      expressed in the regenerative crypt compartment of the colon, small intestine,
      and stomach, and has been found to be abnormally overexpressed as an early event
      in the dysplasia-carcinoma sequences of both ulcerative colitis-related and
      gastric neoplasias. This study was undertaken to evaluate the role of bcl-2 in
      the Barrett's metaplasia-dysplasia-carcinoma sequence. Thirty-six esophageal
      resection specimens were studied, using a monoclonal antibody to the bcl-2
      protein on fixed paraffin-embedded specimens. Barrett's mucosa was present in
      each specimen: low-grade dysplasia in 35, high-grade dysplasia in 34,
      intramucosal carcinoma (IMC) in 23, and submucosal carcinoma in 13. In addition,
      a section of the gastric resection margin was evaluated for bcl-2
      immunoreactivity in each case. In all cases, the regenerative compartment of the
      gastric mucosa in the resection margins stained for bcl-2; however, no
      immunoreactivity was seen in any of the cases of Barrett's mucosa with or without
      dysplasia or carcinoma. We conclude that, in contrast to its role in gastric
      neoplasia, bcl-2 alterations are not an important molecular marker in the
      neoplastic progression of Barrett's mucosa.

PMID- 8552578
TI  - Brief report: detection of high-molecular-weight cytokeratins in neoplastic and
      non-neoplastic thyroid tumors using microwave antigen retrieval.
AB  - Previous studies have demonstrated the utility of immunohistochemical staining
      for high-molecular-weight cytokeratins in the distinction of papillary carcinoma
      from other neoplasms of the thyroid, however, this technique was reliable only
      when applied to frozen tissues. Our objective in this study was to evaluate the
      use of this antibody in diagnostic thyroid pathology using paraffin-embedded
      materials with microwave antigen retrieval. We studied 89 thyroid tumors
      including 45 papillary carcinomas, 28 nodular hyperplasias, 10 follicular
      adenomas, and 6 follicular carcinomas. Moderate-to-strong diffuse staining was
      confined to papillary carcinoma, whereas follicular neoplasms and hyperplastic
      nodules were either negative or showed focal staining. These results confirm the
      utility of high-molecular-weight cytokeratins immunostaining in diagnostic
      thyroid pathology, and obviate the need for frozen material to apply this method.
      As paraffin-embedded tissues are more readily available, we recommend the use of
      high-molecular-weight cytokeratins with microwave antigen retrieval in cases in
      which it is difficult to distinguish papillary carcinoma from other thyroid
      tumors.

PMID- 8552579
TI  - Emphysema: concepts under change--a pathologist's perspective.
AB  - The diagnosis of pulmonary emphysema is often neither as obvious nor as easy as
      is generally assumed. In this review, the methodologies are discussed by which
      emphysema can be accurately diagnosed. The classification of emphysema is
      outlined, with the salient gross and microscopic features listed.

PMID- 8552580
TI  - Transformation of ovarian dysgerminoma to yolk sac tumor: evidence for a
      histogenetic continuum.
AB  - Dysgerminoma has traditionally been considered an end-stage neoplasm without
      potential for further differentiation. Although there have been several reports
      of transformation of testicular seminoma to yolk sac tumor, a similar event has
      not been previously reported in dysgerminoma of the ovary. Three cases of ovarian
      germ cell tumor (two pure dysgerminomas and one mixed germ cell tumor with
      dysgerminoma and yolk sac components) that revealed histologic changes compatible
      with early transformation to yolk sac tumor are described. In general, the areas
      of transformation were located at the periphery of the tumor lobules which
      otherwise had features of typical dysgerminoma. They were characterized by the
      presence of microcysts and small glandular structures, which though not readily
      identified on H&E became more evident with stains for keratins, alpha
      fetoprotein, and blood group-related antigen. The small size and focal nature of
      change, and the apparent transition favor the interpretation that this change
      represents transformation rather than admixture of two germ cell components. The
      relationship of dysgerminoma to the solid variant of yolk sac tumor is discussed
      and an alternate histogenetic scheme in which dysgerminoma represents the stage
      of earliest differentiation from which other non dysgerminomatous tumors may
      arise is presented. Although previously proposed for testicular germ cell
      neoplasia, this scheme has not yet been applied to their ovarian counterparts.

PMID- 8552581
TI  - Correspondence re: Ivan Damjanov. Saxon genitive of eponyms. Mod Pathol 8:343,
      1995.

PMID- 8552582
TI  - Binding in the growth hormone receptor complex.
AB  - Binding reactions between human growth hormone (hGH) and its receptor provide a
      detailed account of how a polypeptide hormone activates its receptor and more
      generally how proteins interact. Through high-resolution structural and
      functional studies it is seen that hGH uses two different sites (site 1 and site
      2) to bind two identical receptor molecules. This sequential dimerization
      reaction activates the receptor, presumably by bringing the intracellular domains
      into close proximity so they may activate cytosolic components. As a consequence
      of this mechanism it is possible to build antagonists to the receptor by
      introducing mutations in hGH that block binding at site 2 and to build even more
      potent antagonists by combining these with mutants that enhance binding at site
      1. Alanine-scanning mutagenesis of all contact residues at the site 1 interface
      shows that only a small and complementary set of side chains clustered near the
      center of the interface affects binding. The most important contacts are
      hydrophobic, and these are surrounded by polar and charged interactions of lesser
      importance. Kinetic analysis shows for the most part that the important side
      chains function to maintain the complex, not to guide the hormone to the
      receptor. Hormone-induced homodimerization or heterodimerization reactions are
      turning out to be pervasive mechanisms for signal transduction. Moreover, the
      molecular recognition principles seen in the hGH-receptor complex are likely to
      generalize to other protein-protein complexes.

PMID- 8552583
TI  - Receptor-mediated gene transfer into macrophages.
AB  - Gene transfer systems targeting various receptors have been developed to
      introduce functional genes into cells in culture and into intact animals. A
      synthetic molecular conjugate, consisting of mannosylated polylysine that
      exploits endocytosis via the macrophage mannose receptor, was constructed and
      complexed to expression plasmids containing either the Photinus pyralis
      luciferase or Escherichia coli beta-galactosidase (lacZ) reporter genes. The DNA
      complexes were used to transfect murine macrophages isolated from peritoneal
      exudates in vitro. Luciferase and beta-galactosidase activity was found in
      transfected cells in culture, whereas complexes consisting of an irrelevant
      plasmid bound to mannosylated polylysine or the expression plasmid bound to
      galactosylated polylysine resulted in no detectable transgene expression. Gene
      transfer was inhibited by the addition of excess mannosylated bovine serum
      albumin to the culture medium before transfection. Reporter genes were also
      transferred into macrophages residing in the spleen and liver of adult animals
      using this system. Luciferase activity was maximal at 4 days after transfection
      and decreased to lower levels by 16 days. Transgene expression conformed to the
      distribution of cells that had nonspecific esterase, a cytochemical marker for
      macrophages. Thus, this system can be used to introduce functional genes into
      macrophages and may be an approach to the treatment of storage diseases that
      affect the reticuloendothelial system.

PMID- 8552584
TI  - A two-subunit type I DNA topoisomerase (reverse gyrase) from an extreme
      hyperthermophile.
AB  - A recently described reverse gyrase from the hyperthermophilic methanogen
      Methanopyrus kandleri is the only known example of a heterodimeric type I
      topoisomerase. The enzyme is made up of a 42-kDa subunit which covalently
      interacts with DNA (RgyA) and a 138-kDa subunit which binds ATP (RgyB). We have
      now cloned and sequenced the genes for both subunits of this enzyme.
      Surprisingly, the universally conserved type I topoisomerase domain [Lima, C. D.,
      Wang, J. C. & Mondragon, A. (1994) Nature (London) 367, 138-146] which has been
      found as a contiguous polypeptide in the prokaryotes and eukaryotes is shared
      between the protomers. The subdomain with the active-site tyrosine is entirely
      within RgyA, whereas the subdomain implicated in noncovalent binding of the
      cleaved DNA strand is contained entirely in RgyB. The appearance of this unique
      structure in a highly conserved enzyme family supports the hypothesis that the
      methanogens branched from other prokaryotes and eukaryotes very early in
      evolution.

PMID- 8552585
TI  - Vpr protein of human immunodeficiency virus type 1 forms cation-selective
      channels in planar lipid bilayers.
AB  - A small (96-aa) protein, virus protein R (Vpr), of human immunodeficiency virus
      type 1 contains one hydrophobic segment that could form a membrane-spanning
      helix. Recombinant Vpr, expressed in Escherichia coli and purified by affinity
      chromatography, formed ion channels in planar lipid bilayers when it was added to
      the cis chamber and when the trans chamber was held at a negative potential. The
      channels were more permeable to Na+ than to Cl- ions and were inhibited when the
      trans potential was made positive. Similar channel activity was caused by Vpr
      that had a truncated C terminus, but the potential dependence of channel activity
      was no longer seen. Antibody raised to a peptide mimicking part of the C terminus
      of Vpr (AbC) inhibited channel activity when added to the trans chamber but had
      no effect when added to the cis chamber. Antibody to the N terminus of Vpr (AbN)
      increased channel activity when added to the cis chamber but had no effect when
      added to the trans chamber. The effects of potential and antibodies on channel
      activity are consistent with a model in which the positive C-terminal end of
      dipolar Vpr is induced to traverse the bilayer membrane when the opposite (trans)
      side of the membrane is at a negative potential. The C terminus of Vpr would then
      be available for interaction with AbC in the trans chamber, and the N terminus
      would be available for interaction with AbN in the cis chamber. The ability of
      Vpr to form ion channels in vitro suggests that channel formation by Vpr in vivo
      is possible and may be important in the life cycle of human immunodeficiency
      virus type 1 and/or may cause changes in cells that contribute to AIDS-related
      pathologies.

PMID- 8552586
TI  - The human thyrotropin receptor: a heptahelical receptor capable of stimulating
      members of all four G protein families.
AB  - Thyrotropin is the primary hormone that, via one heptahelical receptor, regulates
      thyroid cell functions such as secretion, specific gene expression, and growth.
      In human thyroid, thyrotropin receptor activation leads to stimulation of the
      adenylyl cyclase and phospholipase C cascades. However, the G proteins involved
      in thyrotropin receptor action have been only partially defined. In membranes of
      human thyroid gland, we immunologically identified alpha subunits of the G
      proteins Gs short, Gs long, Gi1, Gi2, Gi3, G(o) (Go2 and another form of Go,
      presumably Go1), Gq, G11, G12, and G13. Activation of the thyrotropin (TSH)
      receptor by bovine TSH led to increased incorporation of the photoreactive GTP
      analogue [alpha-32P]GTP azidoanilide into immunoprecipitated alpha subunits of
      all G proteins detected in thyroid membranes. This effect was receptor-dependent
      and not due to direct G protein stimulation because it was mimicked by TSH
      receptor-stimulating antibodies of patients suffering from Grave disease and was
      abolished by a receptor-blocking antiserum from a patient with autoimmune
      hypothyroidism. The TSH-induced activation of individual G proteins occurred with
      EC50 values of 5-50 milliunits/ml, indicating that the activated TSH receptor
      coupled with similar potency to different G proteins. When human thyroid slices
      were pretreated with pertussis toxin, the TSH receptor-mediated accumulation of
      cAMP increased by approximately 35% with TSH at 1 milliunits/ml, indicating that
      the TSH receptor coupled to Gs and G(i). Taken together, these findings show
      that, at least in human thyroid membranes, in which the protein is expressed at
      its physiological levels, the TSH receptor resembles a naturally occurring
      example of a general G protein-activating receptor.

PMID- 8552587
TI  - Influence of alkyltransferase activity and chromosomal locus on mutational
      hotspots in Chinese hamster ovary cells.
AB  - High-density mutational spectra have been established for exon 3 of the gene
      encoding adenine phosphoribosyltransferase (APRT) of the Chinese hamster ovary
      (CHO) cell line derivative D422 and closely related and/or modified lines by
      using the mutagen ethyl methanesulfonate (EMS). The total number of selectable
      sites (GC-->AT transitions yielding a selectable APRT- phenotype) was estimated
      at 31 based on our own accumulated data base of 136 sequenced exon 3 mutations
      and on literature reports. D422 and two other APRT hemizygous lines each yielded
      very similar spectra and showed two populations of mutable sites: (i) 24
      "baseline" sites that followed the Poisson distribution and therefore were
      equally susceptible to mutation and (ii) two hotspots, one comprising a cluster
      at nucleotides 1293-1309 and the other at nucleotide 1365. Collectively, the
      latter sites were about 10-fold more frequently mutated than the others. CHO
      cells are mer- as they lack the repair enzyme O6-methylguanidine
      methyltransferase (EC 2.1.1.63). In modified repair-proficient CHO cells, the
      distribution of mutations among all of the 31 sites was random, with only 3 of
      the 19 GC-->AT transitions in the above hotspots. To determine whether the
      distribution was locus-dependent, two independent lines carrying single copies of
      transfected APRT genes were generated from a derivative of D422 carrying a
      deletion in the endogenous APRT gene. Nucleotides 1293-1309 were again no longer
      preferentially mutated, but the site at nucleotide 1365 was still a hotspot. We
      conclude that mutational spectra in mer- cells are at least in part locus
      dependent and that some sequences are particularly susceptible to EMS mutagenesis
      and perhaps also to methyltransferase repair.

PMID- 8552588
TI  - Integration of complete transferred DNA units is dependent on the activity of
      virulence E2 protein of Agrobacterium tumefaciens.
AB  - Agrobacterium tumefaciens transfers transferred DNA (T-DNA), a single-stranded
      segment of its tumor-inducing (Ti) plasmid, to the plant cell nucleus. The Ti
      plasmid-encoded virulence E2 (VirE2) protein expressed in the bacterium has
      single-stranded DNA (ssDNA)-binding properties and has been reported to act in
      the plant cell. This protein is thought to exert its influence on transfer
      efficiency by coating and accompanying the single-stranded T-DNA (ss-T-DNA) to
      the plant cell genome. Here, we analyze different putative roles of the VirE2
      protein in the plant cell. In the absence of VirE2 protein, mainly truncated
      versions of the T-DNA are integrated. We infer that VirE2 protects the ss-T-DNA
      against nucleolytic attack during the transfer process and that it is interacting
      with the ss-T-DNA on its way to the plant cell nucleus. Furthermore, the VirE2
      protein was found not to be involved in directing the ss-T-DNA to the plant cell
      nucleus in a manner dependent on a nuclear localization signal, a function which
      is carried by the NLS of VirD2. In addition, the efficiency of T-DNA integration
      into the plant genome was found to be VirE2 independent. We conclude that the
      VirE2 protein of A. tumefaciens is required to preserve the integrity of the T
      DNA but does not contribute to the efficiency of the integration step per se.

PMID- 8552589
TI  - Principles of protein-protein interactions.
AB  - This review examines protein complexes in the Brookhaven Protein Databank to gain
      a better understanding of the principles governing the interactions involved in
      protein-protein recognition. The factors that influence the formation of protein
      protein complexes are explored in four different types of protein-protein
      complexes--homodimeric proteins, heterodimeric proteins, enzyme-inhibitor
      complexes, and antibody-protein complexes. The comparison between the complexes
      highlights differences that reflect their biological roles.

PMID- 8552590
TI  - Identification, sequence, and expression of caveolin-2 defines a caveolin gene
      family.
AB  - Caveolin, a 21- to 24-kDa integral membrane protein, is a principal component of
      caveolae membranes. Caveolin interacts directly with heterotrimeric guanine
      nucleotide binding proteins (G proteins) and can functionally regulate their
      activity. Here, an approximately 20-kDa caveolin-related protein, caveolin-2, was
      identified through microsequencing of adipocyte-derived caveolin-enriched
      membranes; caveolin was retermed caveolin-1. Caveolins 1 and 2 are similar in
      most respects. mRNAs for both caveolin-1 and caveolin-2 are most abundantly
      expressed in white adipose tissue and are induced during adipocyte
      differentiation. Caveolin-2 colocalizes with caveolin-1, indicating that caveolin
      2 also localizes to caveolae. However, caveolin-1 and caveolin-2 differ in their
      functional interactions with heterotrimeric G proteins, possibly explaining why
      caveolin-1 and -2 are coexpressed within a single cell.

PMID- 8552591
TI  - Molecular cloning of mesothelin, a differentiation antigen present on
      mesothelium, mesotheliomas, and ovarian cancers.
AB  - Monoclonal antibody MAb K1 recognizes a 40-kDa glycoprotein present on the
      surface of mesothelial cells, mesotheliomas, and ovarian cancers. We have used
      MAb K1 to isolate a 2138-bp cDNA that encodes this antigen. The cDNA has an 1884
      bp open reading frame encoding a 69-kDa protein. When the cDNA was transfected
      into COS and NIH 3T3 cells, the antigen was found on the cell surface and could
      be released by treatment with phosphatidylinositol-specific phospholipase C. The
      69-kDa precursor is processed to the 40-kDa form. The protein has been named
      mesothelin because it is made by mesothelial cells. Mesothelin may play a role in
      cellular adhesion.

PMID- 8552592
TI  - Cytoplasmic dynein is associated with slow axonal transport.
AB  - Neuronal function is dependent on the transport of materials from the cell body
      to the synapse via anterograde axonal transport. Anterograde axonal transport
      consists of several components that differ in both rate and protein composition.
      In fast transport, membranous organelles are moved along microtubules by the
      motor protein kinesin. The cytoskeleton and the cytomatrix proteins move in the
      two components of slow transport. While the mechanisms underlying slow transport
      are unknown, it has been hypothesized that the movement of microtubules in slow
      transport is generated by sliding. To determine whether dynein, a motor protein
      that causes microtubule sliding in flagella, may play a role in slow axonal
      transport, we identified the transport rate components with which cytoplasmic
      dynein is associated in rat optic nerve. Nearly 80% of the anterogradely moving
      dynein was associated with slow transport, whereas only approximately 15% of the
      dynein was associated with the membranous organelles of anterograde fast axonal
      transport. A segmental analysis of the transport of dynein through contiguous
      regions of the optic nerve and tract showed that dynein is associated with the
      microfilaments and other proteins of slow component b. Dynein from this transport
      component has the capacity to bind microtubules in vitro. These results are
      consistent with the hypothesis that cytoplasmic dynein generates the movement of
      microtubules in slow axonal transport. A model is presented to illustrate how
      dynein attached to the slow component b complex of proteins is appropriately
      positioned to generate force of the correct polarity to slide microtubules down
      the axon.

PMID- 8552593
TI  - Embryonic stem cells express multiple Eph-subfamily receptor tyrosine kinases.
AB  - Eph and its homologues form the largest subfamily of receptor tyrosine kinases.
      Normal expression patterns of this subfamily indicate roles in differentiation
      and development, whereas their overexpression has been linked to oncogenesis.
      This study investigated the potential role of Eph-related molecules during very
      early embryonic development by examining their expression in embryonic stem (ES)
      cells and embryoid bodies differentiated from ES cells in vitro. By use of a
      strategy based on reverse transcriptase-mediated PCR, nine clones containing Eph
      subfamily sequence were isolated from ES cells. Of these, eight were almost
      identical to one of four previously identified molecules (Sek, Nuk, Eck, and
      Mek4). However, one clone contained sequence from a novel Eph-subfamily member,
      which was termed embryonic stem-cell kinase or Esk. Northern analysis showed
      expression of Esk in ES cells, embryoid bodies, day 12 mouse embryos, and some
      tissues of the adult animal. Levels of expression were similar in ES cells and
      embryoid bodies. By comparison, Mek4 showed no significant transcription in the
      ES cell cultures by Northern analysis, whereas Eck displayed stronger signals in
      ES cells than in the embryoid bodies. These results suggest that Eph-subfamily
      molecules may play roles during the earliest phases of embryogenesis.
      Furthermore, the relative importance of different members of this subfamily
      appears to change as development proceeds.

PMID- 8552594
TI  - Platelet-derived growth factor activates protein kinase C epsilon through
      redundant and independent signaling pathways involving phospholipase C gamma or
      phosphatidylinositol 3-kinase.
AB  - Protein kinase C (PKC), a major cellular receptor for tumor-promoting phorbol
      esters and diacylglycerols (DGs), appears to be involved in a variety of cellular
      functions, although its activation mechanism in vivo is not yet fully understood.
      To evaluate the signaling pathways involved in the activation of PKC epsilon upon
      stimulation by platelet-derived growth factor (PDGF) receptor (PDGFR), we used a
      series of PDGFR "add-back" mutants. Activation of a PDGFR mutant (Y40/51) that
      binds and activates phosphatidylinositol 3-kinase (PI 3-kinase) caused
      translocation of PKC epsilon from the cytosol to the membrane in response to
      PDGF. A PDGFR mutant (Y1021) that binds and activates phospholipase C gamma (PLC
      gamma), but not PI 3-kinase, also caused the PDGF-dependent translocation of PKC
      epsilon. The translocation of PKC epsilon upon stimulation of PDGFR (Y40/51) was
      inhibited by wortmannin, an inhibitor of PI 3-kinase. Activation of PKC epsilon
      was further confirmed in terms of PKC epsilon-dependent expression of a phorbol
      12-tetradecanoate 13-acetate response element (TRE)-luciferase reporter. Further,
      purified PKC epsilon was activated in vitro by either DG or synthetic
      phosphatidylinositol 3,4,5-trisphosphate. These results clearly demonstrate that
      PKC epsilon is activated through redundant and independent signaling pathways
      which most likely involve PLC gamma or PI 3-kinase in vivo and that PKC epsilon
      is one of the downstream mediators of PI 3-kinase whose downstream targets remain
      to be identified.

PMID- 8552595
TI  - Angiotensin II type 2 receptor mediates programmed cell death.
AB  - The function of the recently discovered angiotensin II type 2 (AT2) receptor
      remains elusive. This receptor is expressed abundantly in fetus, but scantily in
      adult tissues except brain, adrenal medulla, and atretic ovary. In this study, we
      demonstrated that this receptor mediates programmed cell death (apoptosis). We
      observed this effect in PC12W cells (rat pheochromocytoma cell line) and R3T3
      cells (mouse fibroblast cell line), which express abundant AT2 receptor but not
      AT1 receptor. The cellular mechanism appears to involve the dephosphorylation of
      mitogen-activated protein kinase (MAP kinase). Vanadate, a protein-tyrosine
      phosphatase inhibitor, attenuated the dephosphorylation of MAP kinases by the AT2
      receptor and restored the apoptotic changes. Antisense oligonucleotide to MAP
      kinase phosphatase 1 inhibited the AT2 receptor-mediated MAP kinase
      dephosphorylation and blocked the AT2 receptor-mediated apoptosis. These results
      suggest that protein-tyrosine-phosphatase, including MAP kinase phosphatase 1
      activated by the AT2 receptor, is involved in apoptosis. We hypothesize that this
      apoptotic function of the AT2 receptor may play an important role in
      developmental biology and pathophysiology.

PMID- 8552596
TI  - HLA-G expression during preimplantation human embryo development.
AB  - HLA-G is a nonclassical class I major histocompatibility complex molecule with a
      restricted pattern of expression that includes the placental extravillus
      cytotrophoblast cells in direct contact with maternal tissues. Circumstantial
      evidence suggests that HLA-G may play a role in protection of the semiallogeneic
      human fetus. We examined whether HLA-G is expressed during the critical period of
      preimplantation human development and whether expression of this molecule could
      be correlated with the cleavage rate of embryos. Using reverse transcription PCR
      on surplus human embryos and unfertilized oocytes from patients undergoing in
      vitro fertilization we detected HLA-G heavy chain mRNA in 40% of 148 of
      blastocysts tested. The presence of HLA-G mRNA was also detected in unfertilized
      oocytes and in early embryos, but not in control cumulus oophorus cells. beta 2
      Microglobulin mRNA was also found in those embryos expressing HLA-G. In
      concordance with our mRNA data, a similar proportion of embryos stained positive
      for HLA-G utilizing a specific monoclonal antibody. Interestingly, expression of
      HLA-G mRNA was associated with an increased cleavage rate, as compared to embryos
      lacking HLA-G transcript. Thus, HLA-G could be a functional homologue of the
      mouse Qa-2 antigen, which has been implicated in differences in the rate of
      preimplantation embryo development. To our knowledge, the presence of HLA-G mRNA
      and protein in human preimplantation embryos and oocytes has not been reported
      previously. The correlation of HLA-G mRNA expression with cleavage rate suggests
      that this molecule may play an important role in human pre-embryo development.

PMID- 8552597
TI  - Evidence that two present-day components needed for the genetic code appeared
      after nucleated cells separated from eubacteria.
AB  - The trinucleotide/amino acid relationships of the present-day genetic code are
      established by the amino-acylation reactions of tRNA synthetases, whereby each of
      20 specific amino acids is attached to its cognate tRNAs, which bear anticodon
      trinucleotides. Because of its universality, the appearance of the modern genetic
      code is thought to predate the separation of prokaryotic and eukaryotic organisms
      in the universal phylogenetic tree. In the light of new sequence information, we
      present here a phylogenetic analysis that shows an unusual picture for tyrosyl-
      and tryptophanyl-tRNA synthetases. Ij particular, the eukaryotic tyrosyl- and
      tryptophanyl-tRNA synthetases are more related to each other than to their
      respective prokaryotic counterparts. In contrast, each of the other 18 eukaryotic
      synthetases is more related to its prokaryotic counterpart than to any eukaryotic
      synthetase specific for a different amino acid. Our results raise the possibility
      that present day tyrosyl- and tryptophanyl-tRNA synthetases appeared after the
      separation of nucleated cells from eubacteria. The results have implications for
      the development of the genetic code.

PMID- 8552598
TI  - Structural variation of the pseudoautosomal region between and within inbred
      mouse strains.
AB  - The pseudoautosomal region (PAR) is a segment of shared homology between the sex
      chromosomes. Here we report additional probes for this region of the mouse
      genome. Genetic and fluorescence in situ hybridization analyses indicate that one
      probe, PAR-4, hybridizes to the pseudoautosomal telomere and a minor locus at the
      telomere of chromosome 9 and that a PCR assay based on the PAR-4 sequence
      amplifies only the pseudoautosomal locus (DXYHgu1). The region detected by PAR-4
      is structurally unstable; it shows polymorphism both between mouse strains and
      between animals of the same inbred strain, which implies an unusually high
      mutation rate. Variation occurs in the region adjacent to a (TTAGGG)n array. Two
      pseudoautosomal probes can also hybridize to the distal telomeres of chromosomes
      9 and 13, and all three telomeres contain DXYMov15. The similarity between these
      telomeres may reflect ancestral telomere-telomere exchange.

PMID- 8552599
TI  - Mutagenic specificity of solar UV light in nucleotide excision repair-deficient
      rodent cells.
AB  - To investigate the role of nucleotide excision repair (NER) in the cellular
      processing of carcinogenic DNA photoproducts induced by defined, environmentally
      relevant portions of the solar wavelength spectrum, we have determined the
      mutagenic specificity of simulated sunlight (310-1100 nm), UVA (350-400 nm), and
      UVB (290-320 nm), as well as of the "nonsolar" model mutagen 254-nm UVC, at the
      adenine phosphoribosyltransferase (aprt) locus in NER-deficient (ERCC1) Chinese
      hamster ovary (CHO) cells. The frequency distributions of mutational classes
      induced by UVB and by simulated sunlight in repair-deficient CHO cells were
      virtually identical, each showing a marked increase in tandem CC-->TT transitions
      relative to NER-proficient cells. A striking increase in CC-->TT events was also
      previously documented for mutated p53 tumor-suppressor genes from nonmelanoma
      tumors of NER-deficient, skin cancer-prone xeroderma pigmentosum patients,
      compared to normal individuals. The data therefore indicate that the aprt gene in
      NER-deficient cultured rodent cells irradiated with artificial solar light
      generates the same distinctive "fingerprint" for sunlight mutagenesis as the p53
      locus in NER-deficient humans exposed to natural sunlight in vivo. Moreover, in
      strong contrast to the situation for repair-component CHO cells, where a
      significant role for UVA was previously noted, the mutagenic specificity of
      simulated sunlight in NER-deficient CHO cells and of natural sunlight in humans
      afflicted with xeroderma pigmentosum can be entirely accounted for by the UVB
      portion of the solar wavelength spectrum.

PMID- 8552600
TI  - Molecular phylogeny of the extinct ground sloth Mylodon darwinii.
AB  - DNA was extracted from the remains of 35 ground sloths from various parts of
      North and South America. Two specimens of Mylodon darwinii, a species that went
      extinct at the end of the last glaciation, yielded amplifiable DNA. However, of
      the total DNA extracted, only approximately 1/1000 originated from the sloth,
      whereas a substantial part of the remainder was of bacterial and fungal origin.
      In spite of this, > 1100 bp of sloth mitochondrial rDNA sequences could be
      reconstructed from short amplification products. Phylogenetic analyses using
      homologous sequences from all extant edentate groups suggest that Mylodon
      darwinii was more closely related to the two-toed than the three-toed sloths and,
      thus, that an arboreal life-style has evolved at least twice among sloths. The
      divergence of Mylodon and the two-toed sloth furthermore allows a date for the
      radiation of armadillos, anteaters, and sloths to be estimated. This result shows
      that the edentates differ from other mammalian orders in that they contain
      lineages that diverged before the end of the Cretaceous Period.

PMID- 8552601
TI  - Cloning and characterization of ERG25, the Saccharomyces cerevisiae gene encoding
      C-4 sterol methyl oxidase.
AB  - We have cloned the Saccharomyces cerevisiae C-4 sterol methyl oxidase ERG25 gene.
      The sterol methyl oxidase performs the first of three enzymic steps required to
      remove the two C-4 methyl groups leading to cholesterol (animal), ergosterol
      (fungal), and stigmasterol (plant) biosynthesis. An ergosterol auxotroph, erg25,
      which fails to demethylate and concomitantly accumulates 4,4-dimethylzy-mosterol,
      was isolated after mutagenesis. A complementing clone consisting of a 1.35-kb Dra
      I fragment encoded a 309-amino acid polypeptide (calculated molecular mass, 36.48
      kDa). The amino acid sequence shows a C-terminal endoplasmic reticulum retrieval
      signal KKXX and three histidine-rich clusters found in eukaryotic membrane
      desaturases and in a bacterial alkane hydroxylase and xylene monooxygenase. The
      sterol profile of an ERG25 disruptant was consistent with the erg25 allele
      obtained by mutagenesis.

PMID- 8552602
TI  - The basic motif-leucine zipper transcription factor Nrl can positively regulate
      rhodopsin gene expression.
AB  - The retinal protein Nrl belongs to a distinct subfamily of basic motif-leucine
      zipper DNA-binding proteins and has been shown to bind extended AP-1-like
      sequence elements as a homo- or heterodimer. Here, we demonstrate that Nrl can
      positively regulate the expression of the photoreceptor cell-specific gene
      rhodopsin. Electrophoretic mobility-shift analysis reveals that a protein(s) in
      nuclear extracts from bovine retina and the Y79 human retinoblastoma cell line
      binds to a conserved Nrl response element (NRE) in the upstream promoter region
      of the rhodopsin gene. Nrl or an antigenically similar protein is shown to be
      part of the bound protein complex by supershift experiments using Nrl-specific
      antiserum. Cotransfection studies using an Nrl-expression plasmid and a
      luciferase reporter gene demonstrate that interaction of the Nrl protein with the
      -61 to -84 region of the rhodopsin promoter (which includes the NRE) stimulates
      expression of the reporter gene in CV-1 monkey kidney cells. This Nrl-mediated
      transactivation is specifically inhibited by coexpression of a naturally
      occurring truncated form of Nrl (dominant negative effect). Involvement of Nrl in
      photoreceptor gene regulation and its continued high levels of expression in the
      adult retina suggest that Nrl plays a significant role in controlling retinal
      function.

PMID- 8552603
TI  - A pre-Columbian Y chromosome-specific transition and its implications for human
      evolutionary history.
AB  - A polymorphic C-->T transition located on the human Y chromosome was found by the
      systematic comparative sequencing of Y-specific sequence-tagged sites by
      denaturing high-performance liquid chromatography. The results of genotyping
      representative global indigenous populations indicate that the locus is
      polymorphic exclusively within the Western Hemisphere. The pre-Columbian T allele
      occurs at > 90% frequency within the native South and Central American
      populations examined, while its occurrence in North America is approximately 50%.
      Concomitant genotyping at the polymorphic tetranucleotide microsatellite DYS19
      locus revealed that the C-->T mutation displayed significant linkage
      disequilibrium with the 186-bp allele. The data suggest a single origin of
      linguistically diverse native Americans with subsequent haplotype differentiation
      within radiating indigenous populations as well as post-Columbian European and
      African gene flow. The mutation may have originated either in North America at a
      very early time during the expansion or before it, in the ancestral population(s)
      from which all Americans may have originated. The analysis of linkage of the
      DYS199 and the DYS19 tetranucleotide loci suggests that the C-->T mutation may
      have occurred around 30,000 years ago. We estimate the nucleotide diversity over
      4.2 kb of the nonrecombining portion of the Y chromosome to be 0.00014. compared
      to autosomes, the majority of variation is due to the smaller effective
      population size of the Y chromosome rather than selective sweeps. There begins to
      emerge a pattern of pronounced geographical localization of Y-specific nucleotide
      substitution polymorphisms.

PMID- 8552604
TI  - The estrogen receptor locus is associated with a major gene influencing litter
      size in pigs.
AB  - Identification of individual major genes affecting quantitative traits in
      livestock species has been limited to date. By using a candidate gene approach
      and a divergent breed cross involving the Chinese Meishan pig, we have shown that
      a specific allele of the estrogen receptor (ER) locus is associated with
      increased litter size. Female pigs from synthetic lines with a 50% Meishan
      background that were homozygous for this beneficial allele produced 2.3 more pigs
      in first parities and 1.5 more pigs averaged over all parities than females from
      the same synthetic lines and homozygous for the undesirable allele. This
      beneficial ER allele was also found in pigs with Large White breed ancestory.
      Analysis of females with Large White breed background showed an advantage for
      females homozygous for the beneficial allele as compared to females homozygous
      for the other allele of more than 1 total pig born. Analyses of growth
      performance test records detected no significant unfavorable associations of the
      beneficial allele with growth and developmental traits. Mapping of the ER gene
      demonstrated that the closest known genes or markers were 3 centimorgans from ER.
      To our knowledge, one of these, superoxide dismutase gene (SOD2), was mapped for
      the first time in the pig. Analysis of ER and these linked markers indicated that
      ER is the best predictor of litter size differences. Introgression of the
      beneficial allele into commercial pig breeding lines, in which the allele was not
      present, and marker-assisted selection for the beneficial allele in lines with
      Meishan and Large White background have begun.

PMID- 8552605
TI  - Increasing DNA repair methyltransferase levels via bone marrow stem cell
      transduction rescues mice from the toxic effects of 1,3-bis(2-chloroethyl)-1
      nitrosourea, a chemotherapeutic alkylating agent.
AB  - The chloroethylnitrosourea (CNU) alkylating agents are commonly used for cancer
      chemotherapy, but their usefulness is limited by severe bone marrow toxicity that
      causes the cumulative depletion of all hematopoietic lineages (pancytopenia).
      Bone marrow CNU sensitivity is probably due to the inefficient repair of CNU
      induced DNA damage; relative to other tissues, bone marrow cells express
      extremely low levels of the O6-methylguanine DNA methyltransferase (MGMT) protein
      that repairs cytotoxic O6-chloroethylguanine DNA lesions. Using a simplified
      recombinant retroviral vector expressing the human MGMT gene under control of the
      phosphoglycerate kinase promoter (PGK-MGMT) we increased the capacity of murine
      bone marrow-derived cells to repair CNU-induced DNA damage. Stable reconstitution
      of mouse bone marrow with genetically modified, MGMT-expressing hematopoietic
      stem cells conferred considerable resistance to the cytotoxic effects of 1,3
      bis(2-chloroethyl)-1-nitrosourea (BCNU), a CNU commonly used for chemotherapy.
      Bone marrow harvested from mice transplanted with PGK-MGMT-transduced cells
      showed extensive in vitro BCNU resistance. Moreover, MGMT expression in mouse
      bone marrow conferred in vivo resistance to BCNU-induced pancytopenia and
      significantly reduced BCNU-induced mortality due to bone marrow hypoplasia. These
      data demonstrate that increased DNA alkylation repair in primitive hematopoietic
      stem cells confers multilineage protection from the myelosuppressive effects of
      BCNU and suggest a possible approach to protecting cancer patients from CNU
      chemotherapy-related toxicity.

PMID- 8552606
TI  - Protein-protein interactions in the rigor actomyosin complex.
AB  - Since it has not been possible to crystallize the actomyosin complex, the x-ray
      structures of the individual proteins together with data obtained by fiber
      diffraction and electron microscopy have been used to build detailed models of
      filamentous actin (f-actin) and the actomyosin rigor complex. In the f-actin
      model, a single monomer uses 10 surface loops and two alpha-helices to make
      sometimes complicated interactions with its four neighbors. In the myosin
      molecule, both the essential and regulatory light chains show considerable
      structural homology to calmodulin. General principles are evident in their mode
      of attachment to the target alpha-helix of the myosin heavy chain. The essential
      light chain also makes contacts with other parts of the heavy chain and with the
      regulatory light chain. The actomyosin rigor interface is extensive, involving
      interaction of a single myosin head with regions on two adjacent actin monomers.
      A number of hydrophobic residues on the apposing faces of actin and myosin
      contribute to the main binding site. This site is flanked on three sides by
      charged myosin surface loops that form predominantly ionic interactions with
      adjacent regions of actin. Hydrogen bonding is likely to play a significant role
      in actin-actin and actin-myosin interactions since many of the contacts involve
      loops. The model building approach used with actomyosin is applicable to other
      multicomponent assemblies of biological interest and is a powerful method for
      revealing molecular interactions and providing insights into the mode of action
      of the assemblies.

PMID- 8552607
TI  - Immunoregulatory properties of ISG15, an interferon-induced cytokine.
AB  - ISG15 is a 15-kDa protein of unique primary amino acid sequence, which is
      transcriptionally regulated by interferon (IFN) alpha and IFN-beta. Because it is
      synthesized in many cell types and secreted from human monocytes and lymphocytes,
      we postulated that ISG15 might act to modulate immune cell function. ISG15
      stimulated B-depleted lymphocyte proliferation in a dose-dependent manner with
      significant proliferation induced by amounts of ISG15 as low as 1 ng/ml (58 pM).
      Maximal stimulation of [3H]thymidine incorporation by B-depleted lymphocytes
      occurred at 6-7 days. Immunophenotyping of ISG15-treated B-depleted lymphocyte
      cultures indicated a 26-fold expansion of natural killer (NK) cells (CD56+). In
      cytotoxicity assays, ISG15 was a potent inducer of cytolytic activity directed
      against both K562 (100 lytic units per 10(6) cells) and Daudi (80 lytic units per
      10(6) cells) tumor cell targets, indicating that ISG15 enhanced lymphokine
      activated killer-like activity. ISG15-induced NK cell proliferation required
      coculturing of T and NK cells, suggesting that soluble factor(s) were required.
      Measurement of ISG15-treated cell culture supernatants for cytokines indicated
      production of IFN-gamma (> 700 units/ml). No interleukin 2 or interleukin 12 was
      detected. IFN-gamma itself failed to stimulate lymphocyte proliferation and
      lymphokine-activated killer cell activation. Further, induced expression of IFN
      gamma mRNA was detected by reverse transcription-PCR in T lymphocytes after ISG15
      treatment but not in NK cells. Enhancement of NK cell proliferation, augmentation
      of non-major histocompatibility complex-restricted cytotoxicity, and induction of
      IFN-gamma from T cells identify ISG15 as a member of the cytokine cascade and
      suggest that it may be responsible for amplifying and directing some of the
      immunomodulatory effects of IFN-alpha or IFN-beta.

PMID- 8552608
TI  - Development and characterization of a rodent model of immune-mediated
      cholangitis.
AB  - The cholangiopathies are a group of hepatobiliary diseases in which intrahepatic
      bile duct epithelial cells, or cholangiocytes, are the target for a variety of
      destructive processes, including immune-mediated damage. We tested the hypothesis
      that cholangitis could be induced in rodents by immunization with highly purified
      cholangiocytes. Inbred Wistar rats were immunized with purified hyperplastic
      cholangiocytes isolated after bile duct ligation from either syngeneic Wistar or
      allogeneic Fischer 344 rats; control rats were immunized with bovine serum
      albumin (BSA) or hepatocytes. After immunization with cholangiocytes, recipient
      animals developed histologic evidence of nonsuppurative cholangitis without
      inflammation in other organs; groups immunized with BSA or hepatocytes showed no
      cholangitis. Immunohistochemical studies revealed that portal tract infiltrates
      around bile ducts consisted of CD3-positive lymphocytes, some of which expressed
      major histocompatibility complex class II antigen; B cells and exogenous
      monocytes/macrophages were essentially absent. Transfer of unfractionated ConA
      stimulated spleen cells from cholangiocyte-immunized (but not BSA-immunized) rats
      into recipients also caused nonsuppurative cholangitis. Moreover, these
      splenocytes from cholangiocyte-immunized (but not BSA-immunized) rats were
      cytotoxic in vitro for cultured rodent cholangiocytes; no cytotoxicity was
      observed against a rat hepatocyte cell line. Also, a specific antibody response
      in sera of cholangiocyte-immunized rats was demonstrated by immunoblots against
      cholangiocyte proteins. Finally, cholangiograms in cholangiocyte-immunized rats
      showed distortion and tortuosity of the entire intrahepatic biliary ductal
      system. This unique rodent model of experimental cholangitis demonstrates the
      importance of immune mechanisms in the pathogenesis of cholangitis and will prove
      useful in exploring the mechanisms by which the immune system targets and damages
      cholangiocytes.

PMID- 8552609
TI  - Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of
      patients with rheumatoid arthritis.
AB  - In patients with rheumatoid arthritis the synovial membrane of the affected joint
      is infiltrated with lymphoid cells which may be arranged in structures resembling
      germinal centers. We have directly isolated such infiltrates to determine whether
      B-cell clones within them are selected and expanded in a process analogous to
      that which normally takes place in the germinal centers in secondary lymphoid
      organs. The data suggest that an antigen-driven process leads to the accumulation
      of B cells in the synovial membrane. The finding of identical sequences in
      consecutive sections suggests that under conditions of chronic stimulation,
      memory B cells may enter a stage of differentiation in which they proliferate
      without further accumulation of somatic mutations. Further we see intraclonal
      diversity which underlines the germinal center-like character of these
      infiltrates and demonstrates that a microenvironment is built up in this
      nonlymphoid tissue which supports antigen-dependent differentiation of B cells.
      This is the first demonstration, to our knowledge, of a germinal center-like
      reaction outside lymphoid tissue.

PMID- 8552612
TI  - Expression of a single-chain HLA class I molecule in a human cell line:
      presentation of exogenous peptide and processed antigen to cytotoxic T
      lymphocytes.
AB  - We have synthesized a recombinant gene encoding a single-chain HLA-A2/beta 2
      microglobulin (beta 2m) molecule by linking beta 2m through its carboxyl terminus
      via a short peptide spacer to HLA-A2 (A*0201). This gene has been expressed in
      the beta 2m-deficient colorectal tumor cell line DLD-1. Transfection of this cell
      with the single-chain construct was associated with conformationally correct cell
      surface expression of a class I molecule of appropriate molecular mass. The
      single-chain HLA class I molecule presented either exogenously added peptide or
      (after interferon-gamma treatment) endogenously processed antigen to an influenza
      A matrix-specific, HLA-A2-restricted cytotoxic T-lymphocyte line. The need for
      interferon gamma for the processing and presentation of endogenous antigen
      suggests that DLD-1 has an antigen-processing defect that can be up-regulated, a
      feature that may be found in other carcinomas. Our data indicate that single
      chain HLA class I constructs can form functional class I molecules capable of
      presenting endogenously processed antigens. Such molecules should be of use for
      functional studies, as well as providing potential anticancer immunotherapeutic
      agents or vaccines.

PMID- 8552611
TI  - The molecular role of the common gamma c subunit in signal transduction reveals
      functional asymmetry within multimeric cytokine receptor complexes.
AB  - The specific signal transduction function of the gamma c subunit in the
      interleukin (IL) 2, IL-4, IL-7, IL-9, and IL-15 receptor complexes remains
      undefined. The present structure-function analyses demonstrated that the entire
      cytoplasmic tail of gamma c could be functionally replaced in the IL-2 receptor
      (IL-2R) signaling complex by a severely truncated erythropoietin receptor
      cytoplasmic domain lacking tyrosine residues. Heterodimerization of IL-2R beta
      with either gamma c or the truncated erythropoietin receptor chain led to an
      array of specific signals normally derived from the native IL-2R despite the
      substitution of Janus kinase JAK2 for JAK3 in the receptor complex. These
      findings thus suggest a model in which the gamma c subunit serves as a common and
      generic "trigger" chain by providing a nonspecific Janus kinase for signaling
      program initiation, while signal specificity is determined by the unique "driver"
      subunit in each of the gamma c- containing receptor complexes. Furthermore, these
      results may have important functional implications for the asymmetric design of
      many cytokine receptor complexes and the evolutionary design of receptor
      subfamilies that share common trigger or driver subunits.

PMID- 8552610
TI  - Potent immunogenicity of the B subunits of Escherichia coli heat-labile
      enterotoxin: receptor binding is essential and induces differential modulation of
      lymphocyte subsets.
AB  - The importance of receptor binding in the potent immunogenicity of Escherichia
      coli heat-labile enterotoxin B subunit (EtxB) was tested by comparing its
      immunogical properties with those of a receptor binding mutant, EtxB(G33D).
      Subcutaneous immunization of EtxB(G33D) resulted in 160-fold reduction in
      antibody titer compared with wild-type EtxB, whereas its oral delivery failed to
      provoke any detectable secretory or serum anti-B subunit responses. Moreover, the
      two proteins induced strikingly different effects on lymphocyte cultures in
      vitro. EtxB, in comparison with EtxB(G33D), caused an increase in the proportion
      of B cells, many of which were activated (CD25+); the complete depletion of CD8+
      T cells; an increase in the activation of CD4+ T cells; and an increase in
      interleukin 2 and a decrease in interferon gamma. These data indicate that EtxB
      exerts profound effects on immune cells, suggesting that its potent
      immunogenicity is dependent not only on efficient receptor-mediated uptake, but
      also on direct receptor-mediated immunomodulation of lymphocyte subsets.

PMID- 8552614
TI  - Loss of high-affinity prostacyclin receptors in platelets and the lack of
      prostaglandin-induced inhibition of platelet-stimulated thrombin generation in
      subjects with spinal cord injury.
AB  - Coronary artery disease is a leading cause of death in individuals with chronic
      spinal cord injury (SCI). However, platelets of those with SCI (n = 30) showed
      neither increased aggregation nor resistance to the antiaggregatory effects of
      prostacyclin when compared with normal controls (n = 30). Prostanoid-induced cAMP
      synthesis was similar in both groups. In contrast, prostacyclin, which completely
      inhibited the platelet-stimulated thrombin generation in normal controls, failed
      to do so in those with SCI. Scatchard analysis of the binding of
      [3H]prostaglandin E1, used as a prostacyclin receptor probe, showed the presence
      of one high-affinity (Kd1 = 8.11 +/- 2.80 nM; n1 = 172 +/- 32 sites per cell) and
      one low-affinity (Kd2 = 1.01 +/- 0.3 microM; n2 = 1772 +/- 226 sites per cell)
      prostacyclin receptor in normal platelets. In contrast, the same analysis in
      subjects with SCI showed significant loss (P < 0.001) of high-affinity receptor
      sites (Kd1 = 6.34 +/- 1.91 nM; n1 = 43 +/- 10 sites per cell) with no significant
      change in the low affinity-receptors (Kd2 = 1.22 +/- 0.23; n2 = 1820 +/- 421).
      Treatment of these platelets with insulin, which has been demonstrated to restore
      both of the high- and low-affinity prostaglandin receptor numbers to within
      normal ranges in coronary artery disease, increased high-affinity receptor
      numbers and restored the prostacyclin effect on thrombin generation. These
      results demonstrate that the loss of the inhibitory effect of prostacyclin on the
      stimulation of thrombin generation was due to the loss of platelet high-affinity
      prostanoid receptors, which may contribute to atherogenesis in individuals with
      chronic SCI.

PMID- 8552613
TI  - Truncation of the class II beta-chain cytoplasmic domain influences the level of
      class II/invariant chain-derived peptide complexes.
AB  - Previous studies have established that antigen presenting cells (APC) expressing
      major histocompatibility complex class II beta chains with truncated cytoplasmic
      domains are impaired in their capacity to activate T cells. While it had been
      widely accepted that this impairment is due to a defect in class II cytoplasmic
      domain-dependent signal transduction, we recently generated transgenic mice
      expressing only truncated class II beta chains, and functional analyses of APC
      from these mice revealed signaling-independent defects in antigen presentation.
      Here, we demonstrate that T cells primed on such transgenic APC respond better to
      stimulation by APC expressing truncated beta chains than by wild-type APC. This
      finding suggests that APC expressing truncated class II beta chains are not
      inherently defective in their antigen presenting capacity but, rather, may differ
      from wild-type APC in the peptide antigens that they present. Indeed, analysis of
      the peptides bound to class II molecules isolated from normal and transgenic
      spleen cells revealed clear differences. Most notably, the level of class II
      associated invariant chain-derived peptides (CLIP) is significantly reduced in
      cells expressing only truncated beta chains. Prior studies have established that
      CLIP and antigenic peptides compete for binding to class II molecules. Thus, our
      results suggest that the cytoplasmic domain of the class II beta chain affects
      antigen presentation by influencing the level of CLIP/class II complexes.

PMID- 8552615
TI  - Isolation and characterization of a cell surface albumin-binding protein from
      vascular endothelial cells.
AB  - Albumin-binding proteins identified in vascular endothelial cells have been
      postulated to contribute to the transport of albumin via a process involving
      transcytosis. In the present study, we have purified and characterized a 57- to
      60-kDa (gp60) putative albumin-binding protein from bovine pulmonary microvessel
      endothelial cells. The endothelial cell membranes were isolated from cultured
      cells by differential centrifugation and solubilized with sodium cholate and
      urea. The solubilized extract was concentrated after dialysis by ethanol
      precipitation and reextracted with Triton X-100, and the resulting extract was
      subjected to DEAE-cellulose column chromatography. Proteins eluted from this
      column were further separated using preparative sodium dodecyl
      sulfate/polyacrylamide gel electrophoresis and used for immunizing rabbits.
      Fluorescence-activated cell sorter analysis using the anti-gp60 antibodies
      demonstrated the expression of gp60 on the endothelial cell surface. Affinity
      purified anti-gp60 antibodies inhibited approximately 90% of the specific binding
      of 125I-labeled albumin to bovine pulmonary microvessel endothelial cell surface.
      The anti-gp60 antibodies reacted with gp60 from bovine pulmonary artery, bovine
      pulmonary microvessel, human umbilical vein, and rat lung endothelial cell
      membranes. Bovine anti-gp60 antibodies also reacted with bovine secreted protein,
      acidic and rich in cysteine (SPARC). However, bovine SPARC NH2-terminal sequence
      (1-56 residues) antibodies did not react with gp60, indicating that the
      endothelial cell-surface-associated albumin-binding protein gp60 was different
      from the secreted albumin-binding protein SPARC. We conclude that the endothelial
      cell-surface-associated gp60 mediates the specific binding of native albumin to
      endothelial cells and thus may regulate the uptake of albumin and its
      transcytosis.

PMID- 8552616
TI  - Molecular mechanisms of dexamethasone inhibition of nitric oxide synthase
      expression in interleukin 1 beta-stimulated mesangial cells: evidence for the
      involvement of transcriptional and posttranscriptional regulation.
AB  - Inducible nitric oxide synthase (iNOS; EC 1.14.13.39) is expressed in rat
      glomerular mesangial cells upon exposure to the inflammatory cytokine interleukin
      1 beta (IL-1 beta). We have reported that nanomolar concentrations of
      dexamethasone suppress IL-1 beta-induced iNOS protein expression and production
      of nitrite, the stable end product of NO formation, without affecting IL-1 beta
      triggered increase in iNOS mRNA levels. We now have studied the mechanisms by
      which dexamethasone suppresses IL-1 beta-stimulated iNOS expression in mesangial
      cells. Surprisingly, nuclear run-on transcription experiments demonstrate that
      dexamethasone markedly attenuates IL-1 beta-induced iNOS gene transcription.
      However, this is counteracted by a prolongation of the half-life of iNOS mRNA
      from 1 h to 2.5 h by dexamethasone. Moreover, dexamethasone drastically reduces
      the amount of iNOS protein by reduction of iNOS mRNA translation and increased
      degradation of iNOS protein. These results indicate that glucocorticoids act at
      multiple levels to regulate iNOS expression, thus providing important insights
      into the treatment of inflammatory diseases.

PMID- 8552617
TI  - Enterococcus faecalis pheromone binding protein, PrgZ, recruits a chromosomal
      oligopeptide permease system to import sex pheromone cCF10 for induction of
      conjugation.
AB  - Conjugative transfer of the plasmid pCF10 by Enterococcus faecalis donor cells
      occurs in response to a peptide sex pheromone, cCF10, secreted by recipients. The
      plasmid-encoded cCF10 binding protein, PrgZ, is similar in sequence to binding
      proteins (OppAs) encoded by oligopeptide permease (opp) operons. Mutation of prgZ
      decreased the sensitivity of donor cells to pheromone, whereas inactivation of
      the chromosomal E. faecalis opp operon abolished response at physiological
      concentrations of pheromone. Affinity chromatography experiments demonstrated the
      interaction of the pheromone with several putative intracellular regulatory
      molecules, including an RNA molecule required for positive regulation of
      conjugation functions. These data suggest that processing of the pheromone signal
      involves recruitment of a chromosomal Opp system by PrgZ and that signaling
      occurs by direct interaction of internalized pheromone with intracellular
      effectors.

PMID- 8552618
TI  - Induction of the WAF1/CIP1 protein and apoptosis in human T-cell leukemia virus
      type I-transformed lymphocytes after treatment with adriamycin by using a p53
      independent pathway.
AB  - The WAF1/CIP1 protein has been identified as a downstream mediator of the tumor
      suppressor p53 in regulating cell cycle progression through a G1-phase check
      point. Recent work has implicated the functional status of p53 as a critical
      determinant in the apoptotic response of certain cell lines to DNA damaging
      agents. By using human T-cell leukemia virus type I-transformed lymphoid cell
      lines that differ in their level and function of wild-type p53, we investigated
      the induction of WAF1/CIP1 and apoptosis after exposure to Adriamycin, a
      genotoxic agent. We found that regardless of the p53 status in these cell lines,
      WAF1/CIP1 RNA was rapidly induced in response to Adriamycin treatment. An
      elevated level of WAF1/CIP1 protein was observed as well. Additionally, we
      demonstrated that apoptosis was induced in all cell lines analyzed despite some
      having functionally inactive p53 protein. Our data suggest that a p53-independent
      pathway may play a role in the apoptotic response observed in some cell lines
      after exposure to DNA damaging agents.

PMID- 8552620
TI  - Functional implications of protein-protein interactions in icosahedral viruses.
AB  - Biological processes often require that a single gene product participate in
      multiple types of molecular interactions. Viruses with quasiequivalent capsids
      provide an excellent paradigm for studying such phenomena because identical
      protein subunits are found in different structural environments. Differences in
      subunit joints may be controlled by protein segments, duplex or single-stranded
      RNA, metal ions, or some combination of these. Each of the virus groups examined
      display a distinctive mechanism for switching interface interactions,
      illustrating the magnitude of options that are likely to be found in other
      biological systems. In addition to determining capsid morphology, assembly
      controls the timing of autocatalytic maturation cleavage of the viral subunits
      that is required for infectivity in picorna-, noda-, and tetraviruses. The
      mechanism of assembly-dependent cleavage is conserved in noda- and tetraviruses,
      although the quaternary structures of the capsids are different as are the
      molecular switches that control subunit interfaces. The function of the cleavage
      in picorna-, noda-, and tetraviruses is probably to release polypeptides that
      participate in membrane translocation of RNA.

PMID- 8552619
TI  - A Schistosoma mansoni fatty acid-binding protein, Sm14, is the potential basis of
      a dual-purpose anti-helminth vaccine.
AB  - Molecular cloning of components of protective antigenic preparations has
      suggested that related parasite fatty acid-binding proteins could form the basis
      of the protective immune crossreactivity between the parasitic trematode worms
      Fasciola hepatica and Schistosoma mansoni. Molecular models of the two parasite
      proteins showed that both molecules adopt the same basic three-dimensional
      structure, consisting of a barrel-shaped molecule formed by 10 antiparallel beta
      pleated strands joined by short loops, and revealed the likely presence of
      crossreactive, discontinuous epitopes principally derived from amino acids in the
      C-terminal portions of the molecules. A recombinant form of the S. mansoni
      antigen, rSm14, protected outbred Swiss mice by up to 67% against challenge with
      S. mansoni cercariae in the absence of adjuvant and without provoking any
      observable autoimmune response. The same antigen also provided complete
      protection against challenge with F. hepatica metacercariae in the same animal
      model. The results suggest that it may be possible to produce a single vaccine
      that would be effective against at least two parasites, F. hepatica and S.
      mansoni, of veterinary and human importance, respectively.

PMID- 8552621
TI  - Early p53 alterations in mouse skin carcinogenesis by UVB radiation:
      immunohistochemical detection of mutant p53 protein in clusters of preneoplastic
      epidermal cells.
AB  - High levels of the p53 protein are immunohistochemically detectable in a majority
      of human nonmelanoma skin cancers and UVB-induced murine skin tumors. These
      increased protein levels are often associated with mutations in the conserved
      domains of the p53 gene. To investigate the timing of the p53 alterations in the
      process of UVB carcinogenesis, we used a well defined murine model (SKH:HR1
      hairless mice) in which the time that tumors appear is predictable from the UVB
      exposures. The mice were subjected to a series of daily UVB exposures, either for
      17 days or for 30 days, which would cause skin tumors to appear around 80 or 30
      weeks, respectively. In the epidermis of these mice, we detected clusters of
      cells showing a strong immunostaining of the p53 protein, as measured with the CM
      5 polyclonal antiserum. This cannot be explained by transient accumulation of the
      normal p53 protein as a physiological response to UVB-induced DNA damage. In
      single exposure experiments the observed transient CM-5 immunoreactivity lasted
      for only 3 days and was not clustered, whereas these clusters were still
      detectable as long as 56 days after 17 days of UVB exposure. In addition,
      approximately 70% of these patches reacted with the mutant-specific monoclonal
      antibody PAb240, whereas transiently induced p53-positive cells did not. In line
      with indicative human data, these experimental results in the hairless mouse
      model unambiguously demonstrate that constitutive p53 alterations are causally
      related to chronic UVB exposure and that they are a very early event in the
      induction of skin cancer by UVB radiation.

PMID- 8552622
TI  - The lpf fimbrial operon mediates adhesion of Salmonella typhimurium to murine
      Peyer's patches.
AB  - We investigated the role of the Salmonella typhimurium fimbrial operon formed by
      the genes lpfABCDE in infection of mice. A mutant in lpfC, the gene encoding the
      fimbrial outer membrane usher, had an approximately 5-fold increased 50% lethal
      dose when administered orally to mice. When mice were infected with a mixture of
      the lpfC mutant and isogenic wild-type S. typhimurium, the lpfC mutant was
      recovered in lower numbers from Peyer's patches, mesenteric lymph nodes, liver,
      and spleen. In an organ culture model using murine intestinal loops, lpfC mutants
      were shown to be associated in lower numbers than wild-type bacteria with Peyer's
      patches but not with villous intestine. The defect of the lpfC mutant in adhesion
      to Peyer's patches could be complemented by introducing lpfABCDE on a cosmid.
      Similarly, heterologous expression of the Salmonella lpf operon in Escherichia
      coli resulted in an increased adhesion to histological thin sections of Peyer's
      patch lymph follicles. Electron microscopic analysis of histological sections
      taken from Peyer's patches after intragastric infection of mice showed that, in
      contrast to the S. typhimurium wild type, the isogenic lpfC mutant did not
      destroy M cells of the follicle-associated epithelium. These data show that the
      Salmonella lpf operon is involved in adhesion to murine Peyer's patches.

PMID- 8552623
TI  - Expression cloning and functional characterization of the kidney cortex high
      affinity proton-coupled peptide transporter.
AB  - The presence of a proton-coupled electrogenic high-affinity peptide transporter
      in the apical membrane of tubular cells has been demonstrated by microperfusion
      studies and by use of brush border membrane vesicles. The transporter mediates
      tubular uptake of filtered di- and tripeptides and aminocephalosporin
      antibiotics. We have used expression cloning in Xenopus laevis oocytes for
      identification and characterization of the renal high-affinity peptide
      transporter. Injection of poly(A)+ RNA isolated from rabbit kidney cortex into
      oocytes resulted in expression of a pH-dependent transport activity for the
      aminocephalosporin antibiotic cefadroxil. After size fractionation of poly(A)+
      RNA the transport activity was identified in the 3.0- to 5.0-kb fractions, which
      were used for construction of a cDNA library. The library was screened for
      expression of cefadroxil transport after injection of complementary RNA
      synthesized in vitro from different pools of clones. A single clone (rPepT2) was
      isolated that stimulated cefadroxil uptake into oocytes approximately 70-fold at
      a pH of 6.0. Kinetic analysis of cefadroxil uptake expressed by the transporter's
      complementary RNA showed a single saturable high-affinity transport system shared
      by dipeptides, tripeptides, and selected amino-beta-lactam antibiotics.
      Electrophysiological studies established that the transport activity is
      electrogenic and affected by membrane potential. Sequencing of the cDNA predicts
      a protein of 729 amino acids with 12 membrane-spanning domains. Although there is
      a significant amino acid sequence identity (47%) to the recently cloned peptide
      transporters from rabbit and human small intestine, the renal transporter shows
      distinct structural and functional differences.

PMID- 8552624
TI  - Reversible visual hemineglect.
AB  - We have identified a limited region in the posterior, but not anterior, half of
      the cat's middle suprasylvian region which, when cooled and inactivated
      unilaterally, results in a profound visual neglect of stimuli introduced into the
      contracooled hemifield. The severity of the deficit matches that induced by
      unilateral cooling of the superior colliculus. The cortical region is located at
      the temporo-occipito-parietal junction and is believed to be equivalent to a
      region centered on or close to the area V5 complex of primates.

PMID- 8552625
TI  - cAMP compartmentation is responsible for a local activation of cardiac Ca2+
      channels by beta-adrenergic agonists.
AB  - The role of cAMP subcellular compartmentation in the progress of beta-adrenergic
      stimulation of cardiac L-type calcium current (ICa) was investigated by using a
      method based on the use of whole-cell patch-clamp recording and a double
      capillary for extracellular microperfusion. Frog ventricular cells were sealed at
      both ends to two patch-clamp pipettes and positioned approximately halfway
      between the mouths of two capillaries that were separated by a 5-micron thin
      wall. ICa could be inhibited in one half or the other by omitting Ca2+ from one
      solution or the other. Exposing half of the cell to a saturating concentration of
      isoprenaline (ISO, 1 microM) produced a nonmaximal increase in ICa (347 +/- 70%;
      n = 4) since a subsequent application of ISO to the other part induced an
      additional effect of nearly similar amplitude to reach a 673 +/- 130% increase.
      However, half-cell exposure to forskolin (FSK, 30 microM) induced a maximal
      stimulation of ICa (561 +/- 55%; n = 4). This effect was not the result of
      adenylyl cyclase activation due to FSK diffusion in the nonexposed part of the
      cell. To determine the distant effects of ISO and FSK on ICa, the drugs were
      applied in a zero-Ca solution. Adding Ca2+ to the drug-containing solutions
      allowed us to record the local effect of the drugs. Dose-response curves for the
      local and distant effects of ISO and FSK on ICa were used as an index of cAMP
      concentration changes near the sarcolemma. We found that ISO induced a 40-fold,
      but FSK induced only a 4-fold, higher cAMP concentration close to the Ca2+
      channels, in the part of the cell exposed to the drugs, than it did in the rest
      of the cell. cAMP compartmentation was greatly reduced after inhibition of
      phosphodiesterase activity with 3-isobutyl-methylxanthine, suggesting the
      colocalization of enzymes involved in the cAMP cascade. We conclude that beta
      adrenergic receptors are functionally coupled to nearby Ca2+ channels via local
      elevations of cAMP.

PMID- 8552626
TI  - Structure of the sodium channel pore revealed by serial cysteine mutagenesis.
AB  - The pores of voltage-gated cation channels are formed by four intramembrane
      segments that impart selectivity and conductance. Remarkably little is known
      about the higher order structure of these critical pore-lining or P segments.
      Serial cysteine mutagenesis reveals a pattern of side-chain accessibility that
      contradicts currently favored structural models based on alpha-helices or beta
      strands. Like the active sites of many enzymes of known structure, the sodium
      channel pore consists of irregular loop regions.

PMID- 8552627
TI  - Purification and characterization of a guanine nucleotide-exchange protein for
      ADP-ribosylation factor from spleen cytosol.
AB  - ADP-ribosylation factors (ARFs) are 20-kDa guanine nucleotide-binding proteins
      and are active in the GTP-bound state and inactive with GDP bound. ARF-GTP has a
      critical role in vesicular transport in several cellular compartments. Conversion
      of ARF-GDP to ARF-GTP is promoted by a guanine nucleotide-exchange protein (GEP).
      We earlier reported the isolation from bovine brain cytosol of a 700-kDa protein
      complex containing GEP activity that was inhibited by brefeldin A (BFA). Partial
      purification yielded an approximately 60-kDa BFA-insensitive GEP that enhanced
      binding of ARF1 and ARF3 to Golgi membranes. GEP has now been purified
      extensively from rat spleen cytosol in a BFA-insensitive, approximately 55-kDa
      form. It activated class I ARFs (ARFs 1 and 3) that were N-terminally
      myristoylated, but not nonmyristoylated ARFs from class-I, II, or III. GEP
      activity required MgCl2. In the presence of 0.6-0.8 mM MgCl2 and 1 mM EDTA,
      binding of guanosine 5'-[gamma[35S]thio]triphosphate ([35S]GTP gamma S) by ARF1
      and ARF3 was equally high without and with GEP. At higher Mg2+ concentrations,
      binding without GEP was much lower; with 2-5 mM MgCl2, GEP-stimulated binding was
      maximal. The rate of GDP binding was much less than that of GTP gamma S with and
      without GEP. Phospholipids were necessary for GEP activity; phosphatidylinositol
      was more effective than phosphatidylserine, and phosphatidic acid was less so.
      Other phospholipids tested were ineffective. Maximal effects required
      approximately 200 microM phospholipid, with half-maximal activation at 15-20
      microM. Release of bound [35S]GTP gamma S from ARF3 required the presence of both
      GEP and unlabeled GTP or GTP gamma S; GDP was much less effective. This
      characterization of the striking effects of Mg2+ concentration and specific
      phospholipids on the purified BFA-insensitive ARF GEP should facilitate
      experiments to define its function in vesicular transport.

PMID- 8552628
TI  - Antibodies against specific extracellular epitopes of the glucagon receptor block
      glucagon binding.
AB  - Polyclonal antibodies were prepared against synthetic peptides corresponding to
      four different extramembrane segments of the rat glucagon receptor. The
      antibodies bound specifically to native glucagon receptor as judged by
      immunofluorescence microscopy of cultured cells expressing a synthetic gene for
      the receptor. Antibodies to peptides designated PR-15 and DK-12 were directed
      against amino acid residues 103-117 and 126-137, respectively, of the
      extracellular N-terminal tail. Antibody to peptide KD-14 was directed against
      residues 206-219 of the first extracellular loop, and antibody to peptide ST-18,
      against the intracellular C-terminal tail, residues 468-485. The DK-12 and KD-14
      antibodies, but not the PR-15 and ST-18 antibodies, could effectively block
      binding of 125I-labeled glucagon to its receptor in liver membranes. Incubation
      of these antibodies with rat liver membranes resulted in both a decrease in the
      maximal hormonal binding capacity and an apparent decrease in glucagon affinity
      for its receptor. These effects were abolished in the presence of excess specific
      peptide antigen. In addition, DK-12 and KD-14 antibodies, but not PR-15 and ST-18
      antibodies, interfered with glucagon-induced adenylyl cyclase activation in rat
      liver membranes and behaved as functional glucagon antagonists. These results
      demonstrate that DK-12 and KD-14 antibodies are pharmacologically active glucagon
      antagonists and strongly suggest that residues 126-137 of the N-terminal tail and
      residues 206-219 of the first extracellular loop contain determinants of ligand
      binding and may comprise the primary ligand-binding site on the glucagon
      receptor.

PMID- 8552629
TI  - Estrogens increase the expression of fibulin-1, an extracellular matrix protein
      secreted by human ovarian cancer cells.
AB  - Ovarian cancers have a high ability to invade the peritoneal cavity and some are
      stimulated by estrogens. In an attempt to understand the mode of action of
      estrogens on these cancer cells and to develop new markers, we have characterized
      estrogen-regulated proteins. This study was aimed at identifying a protein
      secreted by ovarian cancer cells whose level was increased by estradiol [Galtier
      Dereure, F., Capony, F., Maudelonde, T. & Rochefort, H. (1992) J. Clin.
      Endocrinol. Metab. 75, 1497-1502]. By using microprotein sequencing, the 110-kDa
      protein was identified as fibulin-1, a protein of the extracellular matrix that
      binds to fibronectin, laminin, and nidogen. The amount of immunoprecipitated
      fibulin-1 secreted into the medium and present in the cell extract was increased
      up to 10-fold by estradiol in three estrogen-responsive ovarian cancer cell
      lines. By immunohistochemistry fibulin-1 was located in the stroma of several
      ovarian cancers and cysts. The findings highlight a potential role for fibulin-1
      in the spread of ovarian cancer in the peritoneal cavity and/or in distal
      metastases.

PMID- 8552630
TI  - Conscious recollection and the human hippocampal formation: evidence from
      positron emission tomography.
AB  - We used positron emission tomography (PET) to examine the role of the hippocampal
      formation in implicit and explicit memory. Human volunteers studied a list of
      familiar words, and then they either provided the first word that came to mind in
      response to three-letter cues (implicit memory) or tried to recall studied words
      in response to the same cues (explicit memory). There was no evidence of
      hippocampal activation in association with implicit memory. However, priming
      effects on the implicit memory test were associated with decreased activity in
      extrastriate visual cortex. On the explicit memory test, subjects recalled many
      target words in one condition and recalled few words in a second condition,
      despite trying to remember them. Comparisons between the two conditions showed
      that blood-flow increases in the hippocampal formation are specifically
      associated with the conscious recollection of studied words, whereas blood-flow
      increases in frontal regions are associated with efforts to retrieve target
      words. Our results help to clarify some puzzles concerning the role of the
      hippocampal formation in human memory.

PMID- 8552631
TI  - The transcriptional transactivator of simian foamy virus 1 binds to a DNA target
      element in the viral internal promoter.
AB  - The transcriptional transactivator (Tas) of simian foamy virus type 1 strongly
      augments gene expression directed by both the promoter in the viral long terminal
      repeat and the newly discovered internal promoter located within the env gene. A
      region of 121 bp, located immediately 5' to the TATA box in the internal
      promoter, is required for transactivation by Tas. The present study aimed to
      identify the precise Tas-responsive target(s) in this region and to determine the
      role of Tas in transcriptional regulation. By analysis of both clustered-site
      mutations and hybrid promoters in transient expression assays in murine and
      simian cells, two separate sequence elements within this 121-bp region were shown
      to be Tas-dependent transcriptional enhancers. These targets, each < 30 bp in
      length and displaying no apparent sequence homology one to the other, are
      designated the promoter-proximal and promoter-distal elements. By means of the
      gel electrophoresis mobility-shift assays, using purified glutathione S
      transferase-Tas fusion protein expressed in Escherichia coli, the target proximal
      to the TATA box exhibited strong binding to glutathione S-transferase-Tas,
      whereas the distal element appears not to bind. In addition, footprint analysis
      revealed that 26 bp in the promoter proximal element was protected by glutathione
      S-transferase-Tas from DNase I. We propose a model for transactivation of the
      simian foamy virus type 1 internal promoter in which Tas interacts directly with
      the proximal target element positioned immediately 5' to the TATA box. In this
      model, Tas attached to this element is presumed to interact with a component(s)
      of the cellular RNA polymerase II initiation complex and thereby enhance
      transcription directed by the viral internal promoter.

PMID- 8552632
TI  - A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to
      dynamin in nerve terminals.
AB  - Amphiphysin, a major autoantigen in paraneoplastic Stiff-Man syndrome, is an SH3
      domain-containing neuronal protein, concentrated in nerve terminals. Here, we
      demonstrate a specific, SH3 domain-mediated, interaction between amphiphysin and
      dynamin by gel overlay and affinity chromatography. In addition, we show that the
      two proteins are colocalized in nerve terminals and are coprecipitated from brain
      extracts consistent with their interactions in situ. We also report that a region
      of amphiphysin distinct from its SH3 domain mediates its binding to the alpha c
      subunit of AP2 adaptin, which is also concentrated in nerve terminals. These
      findings support a role of amphiphysin in synaptic vesicle endocytosis.

PMID- 8552633
TI  - Control of cell division in Escherichia coli: regulation of transcription of
      ftsQA involves both rpoS and SdiA-mediated autoinduction.
AB  - The conditioning of culture medium by the production of growth-regulatory
      substances is a well-established phenomenon with eukaryotic cells. It has
      recently been shown that many prokaryotes are also capable of modulating growth,
      and in some cases sensing cell density, by production of extracellular signaling
      molecules, thereby allowing single celled prokaryotes to function in some
      respects as multicellular organisms. As Escherichia coli shifts from exponential
      growth to stationary growth, many changes occur, including cell division leading
      to formation of short minicells and expression of numerous genes not expressed in
      exponential phase. An understanding of the coordination between the morphological
      changes associated with cell division and the physiological and metabolic changes
      is of fundamental importance to understanding regulation of the prokaryotic cell
      cycle. The ftsQA genes, which encode functions required for cell division in E.
      coli, are regulated by promoters P1 and P2, located upstream of the ftsQ gene.
      The P1 promoter is rpoS-stimulated and the second, P2, is regulated by a member
      of the LuxR subfamily of transcriptional activators, SdiA, exhibiting features
      characteristic of an autoinduction (quorum sensing) mechanism. The activity of
      SdiA is potentiated by N-acyl-homoserine lactones, which are the autoinducers of
      luciferase synthesis in luminous marine bacteria as well as of pathogenesis
      functions in several pathogenic bacteria. A compound(s) produced by E. coli
      itself during growth in Luria Broth stimulates transcription from P2 in an SdiA
      dependent process. Another substance(s) enhances transcription of rpoS and
      (perhaps indirectly) of ftsQA via promoter P1. It appears that this bimodal
      control mechanism may comprise a fail-safe system, such that transcription of the
      ftsQA genes may be properly regulated under a variety of different environmental
      and physiological conditions.

PMID- 8552634
TI  - Selective pressure of a quinoxaline nonnucleoside inhibitor of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1
      replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu
      74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants.
AB  - The quinoxaline nonnucleoside RT inhibitor (NNRTI) (S)-4-isopropoxycarbonyl-6
      methoxy-3-(methylthiomethyl)-3,4- dihydroquinoxaline-2(1H)-thione (HBY 097) was
      used to select for drug-resistant HIV-1 variants in vitro. The viruses first
      developed mutations affecting the NNRTI-binding pocket, and five of six strains
      displayed the RT G190-->E substitution, which is characteristic for HIV-1
      resistance against quinoxalines. In one variant, a new mutant (G190-->Q) most
      likely evolved from preexisting G190-->E mutants. The negative charge introduced
      by the G190-->E substitution was maintained at that site of the pocket by
      simultaneous selection for V179-->D together with G190-->Q. After continued
      exposure to the drug, mutations at positions so far known to be specific for
      resistance against nucleoside RT inhibitors (NRTIs) (L74-->V/I and V75-->L/I)
      were consistently detected in all cultures. The inhibitory activities of the
      cellular conversion product of 2',3'-dideoxyinosine (ddI, didanosine), 2',3'
      dideoxyadenosine (ddA) and of 2',3'-didehydro-3'-deoxythymidine (d4T, stavudine)
      against these late-passage viruses were shown to be enhanced with the L74-->V/I
      RT mutant virus as compared with the wild-type (wt) HIV-1MN isolate. Clonal
      analysis proved linkage of the codon 74 and codon 75 mutations to the NNRTI
      specific mutations in all RT gene fragments. The nonnucleoside- and nucleoside
      resistance mutation sites are separated by approximately 35 A. We propose that
      the two sites "communicate" through the template-primer which is situated in the
      DNA-binding cleft between these two sites. Quinoxalines cause high selective
      pressure on HIV-1 replication in vitro; however, the implication of these
      findings for the treatment of HIV-1 infection has yet to be determined.

PMID- 8552635
TI  - Bacteriophage lambda N protein alone can induce transcription antitermination in
      vitro.
AB  - Specific and processive antitermination by bacteriophage lambda N protein in vivo
      and in vitro requires the participation of a large number of Escherichia coli
      proteins (Nus factors), as well as an RNA hairpin (boxB) within the nut site of
      the nascent transcript. In this study we show that efficient, though
      nonprocessive, antitermination can be induced by large concentrations of N alone,
      even in the absence of a nut site. By adding back individual components of the
      system, we also show that N with nut+ nascent RNA is much more effective in
      antitermination than is N alone. This effect is abolished if N is competed away
      from the nut+ RNA by adding, in trans, an excess of boxB RNA. The addition of
      NusA makes antitermination by the N-nut+ complex yet more effective. This NusA
      dependent increase in antitermination is lost when delta nut transcripts are
      used. These results suggest the formation of a specific boxB RNA-N-NusA complex
      within the transcription complex. By assuming an equilibrium model, we estimate a
      binding constant of 5 x 10(6) M-1 for the interaction of N alone with the
      transcription complex. This value can be used to estimate a characteristic
      dissociation time of N from the complex that is comparable to the dwell time of
      the complex at an average template position, thus explaining the nonprocessivity
      of the antitermination effect induced by N alone. On this basis, the effective
      dissociation rate of N should be approximately 1000-fold slower from the
      minimally processive (100-600 bp) N-NusA-nut+ transcription complex and
      approximately 10(5)-fold slower from the maximally processive (thousands of base
      pairs) complex containing all of the components of the in vivo N-dependent
      antitermination system.

PMID- 8552636
TI  - Importance of the carboxyl-terminal domain of enzyme I of the Escherichia coli
      phosphoenolpyruvate: sugar phosphotransferase system for phosphoryl donor
      specificity.
AB  - The first protein component of the Escherichia coli phosphoenolpyruvate: sugar
      phosphotransferase system (PTS) is the 64-kDa protein enzyme I (EI), which can be
      phosphorylated by phosphoenolpyruvate (PEP) and carry out phosphotransfer to the
      acceptor heat-stable protein (HPr). The isolated amino-terminal domain (EIN) of
      E. coli EI is no longer phosphorylated by PEP but retains the ability to
      participate in reversible phosphotransfer to HPr. An expression vector was
      constructed for the production of large amounts of EIN, and conditions were
      developed for maximal expression of the protein. A three-column procedure is
      described for purification to homogeneity of EIN; a 500-ml culture yields
      approximately 80 mg of pure protein in about a 75% yield. Intact E. coli EI is
      effective in phosphotransfer from PEP to HPr from E. coli but not to the HPrs
      from Bacillus subtilis or Mycoplasma capricolum. Phosphotransfer from EI to
      enzyme IIAglc (EIIAglc) from E. coli or M. capricolum requires the intermediacy
      of HPr. The phosphorylated form of EIN is capable of more general
      phosphotransfer; it will effect phosphotransfer to HPrs from E. coli, B.
      subtilis, and M. capricolum as well as to EIAglc from E. coli. These studies
      demonstrate that the carboxyl-terminal domain of EI confers on the protein the
      capability to accept a phosphoryl group from PEP as well as a discriminator
      function that allows the intact protein to promote effective phosphoryl transfer
      only to E. coli HPr.

PMID- 8552637
TI  - An inhibitor of p34cdc2/cyclin B that regulates the G2/M transition in Xenopus
      extracts.
AB  - The activity of maturation-promoting factor (MPF), a protein kinase complex
      composed of p34cdc2 and cyclin B, is undetectable during interphase but rises
      abruptly at the G2/M transition to induce mitosis. After the synthesis of cyclin
      B, the suppression of MPF activity before mitosis has been attributed to the
      phosphorylation of p34cdc2 on sites (threonine-14 and tyrosine-15) that inhibit
      its catalytic activity. We previously showed that the activity of the mitotic
      p34cdc2/cyclin B complex is rapidly suppressed when added to interphase Xenopus
      extracts that lack endogenous cyclin B. Here we show that a mutant of p34cdc2
      that cannot be inhibited by phosphorylation (threonine-14-->alanine, tyrosine-15-
      >phenylalanine) is also susceptible to inactivation, demonstrating that
      inhibitory mechanisms independent of threonine-14 and tyrosine-15 phosphorylation
      must exist. We have partially characterized this inhibitory pathway as one
      involving a reversible binding inhibitor of p34cdc2/cyclin B that is tightly
      associated with cell membranes. Kinetic analysis suggests that this inhibitor, in
      conjunction with the kinases that mediate the inhibitory phosphorylations on
      p34cdc2, maintains the interphase state in Xenopus; it may play an important role
      in the exact timing of the G2/M transition.

PMID- 8552638
TI  - Cloning and expression of a gene encoding an integrin-like protein in Candida
      albicans.
AB  - The existence of integrin-like proteins in Candida albicans has been postulated
      because monoclonal antibodies to the leukocyte integrins alpha M and alpha X bind
      to blastospores and germ tubes, recognize a candidal surface protein of
      approximately 185 kDa, and inhibit candidal adhesion to human epithelium. The
      gene alpha INT1 was isolated from a library of C. albicans genomic DNA by
      screening with a cDNA probe from the transmembrane domain of human alpha M. The
      predicted polypeptide (alpha Int1p) of 188 kDa contains several motifs common to
      alpha M and alpha X: a putative I domain, two EF-hand divalent cation-binding
      sites, a transmembrane domain, and a cytoplasmic tail with a single tyrosine
      residue. An internal RGD tripeptide is also present. Binding of anti-peptide
      antibodies raised to potential extracellular domains of alpha Int1p confirms
      surface localization in C. albicans blastopores. By Southern blotting, alpha INT1
      is unique to C. albicans. Expression of alpha INT1 under control of a galactose
      inducible promoter led to the production of germ tubes in haploid Saccharomyces
      cerevisiae and in the corresponding ste12 mutant. Germ tubes were not observed in
      haploid yeast transformed with vector alone, in transformants expressing a
      galactose-inducible gene from Chlamydomonas, or in transformants grown in the
      presence of glucose or raffinose. Transformants producing alpha Int1p bound an
      anti-alpha M monoclonal antibody and exhibited enhanced aggregation. Studies of
      alpha Int1p reveal novel roles for primitive integrin-like proteins in adhesion
      and in STE12-independent morphogenesis.

PMID- 8552640
TI  - Phosphorylation-dependent human immunodeficiency virus type 1 infection and
      nuclear targeting of viral DNA.
AB  - In the replication of human immunodeficiency virus type 1 (HIV-1), gag MA
      (matrix), a major structural protein of the virus, carries out opposing targeting
      functions. During virus assembly, gag MA is cotranslationally myristoylated, a
      modification required for membrane targeting of gag polyproteins. During virus
      infection, however, gag MA, by virtue of a nuclear targeting signal at its N
      terminus, facilitates the nuclear localization of viral DNA and establishment of
      the provirus. We now show that phosphorylation of gag MA on tyrosine and serine
      prior to and during virus infection facilitates its dissociation from the
      membrane, thus allowing it to translocate to the nucleus. Inhibition of gag MA
      phosphorylation either on tyrosine or on serine prevents gag MA-mediated nuclear
      targeting of viral nucleic acids and impairs virus infectivity. The requirement
      for gag MA phosphorylation in virus infection is underscored by our finding that
      a serine/threonine kinase is associated with virions of HIV-1. These results
      reveal a novel level of regulation of primate lentivirus infectivity.

PMID- 8552639
TI  - Efflux pump of the proton antiporter family confers low-level fluoroquinolone
      resistance in Mycobacterium smegmatis.
AB  - Due to the resurgence of tuberculosis and the emergence of multidrug-resistant
      strains, fluoroquinolones (FQ) are being used in selected tuberculosis patients,
      but FQ-resistant strains of Mycobacterium tuberculosis have rapidly begun to
      appear. The mechanisms involved in FQ resistance need to be elucidated if the
      effectiveness of this class of antibiotics is to be improved and prolonged. By
      using the rapid-growing Mycobacterium smegmatis as a model genetic system, a gene
      was selected that confers low-level FQ resistance when present on a multicopy
      plasmid. This gene, lfrA, encodes a putative membrane efflux pump of the major
      facilitator family, which appears to recognize the hydrophilic FQ, ethidium
      bromide, acridine, and some quaternary ammonium compounds. It is homologous to
      qacA from Staphylococcus aureus, tcmA, of Streptomyces glaucescens, and actII and
      mmr, both from Streptomyces coelicoler. Increased expression of lfrA augments the
      appearance of subsequent mutations to higher-level FQ resistance.

PMID- 8552641
TI  - Bathorhodopsin structure in the room-temperature rhodopsin photosequence:
      picosecond time-resolved coherent anti-Stokes Raman scattering.
AB  - Structural changes in the retinal chromophore during the formation of the
      bathorhodopsin intermediate (bathoRT) in the room-temperature rhodopsin (RhRT)
      photosequence (i.e., vision) are examined using picosecond time-resolved coherent
      anti-Stokes Raman scattering. Specifically, the retinal structure assignable to
      bathoRT following 8-ps excitation of RhRT is measured via vibrational Raman
      spectroscopy at a 200-ps time delay where the only intermediate present is
      bathoRT. Significant differences are observed between the C=C stretching
      frequencies of the retinal chromophore at low temperature where bathorhodopsin is
      stabilized and at room temperature where bathorhodopsin is a transient species in
      the RhRT photosequence. These vibrational data are discussed in terms of the
      formation of bathoRT, an important step in the energy storage/transduction
      mechanism of RhRT.

PMID- 8552642
TI  - Phase separation in aqueous solutions of lens gamma-crystallins: special role of
      gamma s.
AB  - We have studied liquid-liquid phase separation in aqueous ternary solutions of
      calf lens gamma-crystallin proteins. Specifically, we have examined two ternary
      systems containing gamma s--namely, gamma IVa with gamma s in water and gamma II
      with gamma s in water. For each system, the phase-separation temperatures (Tph
      (phi)) alpha as a function of the overall protein volume fraction phi at various
      fixed compositions alpha (the "cloud-point curves") were measured. For the gamma
      IVa, gamma s, and water ternary solution, a binodal curve composed of pairs of
      coexisting points, (phi I, alpha 1) and (phi II, alpha II), at a fixed
      temperature (20 degrees C) was also determined. We observe that on the cloud
      point curve the critical point is at a higher volume fraction than the maximum
      phase-separation temperature point. We also find that typically the difference in
      composition between the coexisting phases is at least as significant as the
      difference in volume fraction. We show that the asymmetric shape of the cloud
      point curve is a consequence of this significant composition difference. Our
      observation that the phase-separation temperature of the mixtures in the high
      volume fraction region is strongly suppressed suggests that gamma s-crystallin
      may play an important role in maintaining the transparency of the lens.

PMID- 8552643
TI  - Inhibition of human immunodeficiency virus type 1 and vaccinia virus infection by
      a dominant negative factor of the interferon regulatory factor family expressed
      in monocytic cells.
AB  - ICSBP is a member of the interferon (IFN) regulatory factor (IRF) family that
      regulates expression of type I interferon (IFN) and IFN-regulated genes. To study
      the role of the IRF family in viral infection, a cDNA for the DNA-binding domain
      (DBD) of ICSBP was stably transfected into U937 human monocytic cells. Clones
      that expressed DBD exhibited a dominant negative phenotype and did not elicit
      antiviral activity against vesicular stomatitis virus (VSV) infection upon IFN
      treatment. Most notably, cells expressing DBD were refractory to infection by
      vaccinia virus (VV) and human immunodeficiency virus type 1 (HIV-1). The
      inhibition of VV infection was attributed to defective virion assembly, and that
      of HIV-1 to low CD4 expression and inhibition of viral transcription in DBD
      clones. HIV-1 and VV were found to have sequences in their regulatory regions
      similar to the IFN-stimulated response element (ISRE) to which IRF family
      proteins bind. Accordingly, these viral sequences and a cellular ISRE bound a
      shared factor(s) expressed in U937 cells. These observations suggest a novel host
      virus relationship in which the productive infection of some viruses is regulated
      by the IRF-dependent transcription pathway through the ISRE.

PMID- 8552644
TI  - Oral tolerance in myelin basic protein T-cell receptor transgenic mice:
      suppression of autoimmune encephalomyelitis and dose-dependent induction of
      regulatory cells.
AB  - Orally administered antigens induce a state of immunologic hyporesponsiveness
      termed oral tolerance. Different mechanisms are involved in mediating oral
      tolerance depending on the dose fed. Low doses of antigen generate cytokine
      secreting regulatory cells, whereas high doses induce anergy or deletion. We used
      mice transgenic for a T-cell receptor (TCR) derived from an encephalitogenic T
      cell clone specific for the acetylated N-terminal peptide of myelin basic protein
      (MBP) Ac-1-11 plus I-Au to test whether a regulatory T cell could be generated
      from the same precursor cell as that of an encephalitogenic Th1 cell and whether
      the induction was dose dependent. The MBP TCR transgenic mice primarily have T
      cells of a precursor phenotype that produce interleukin 2 (IL-2) with little
      interferon gamma (IFN-gamma), IL-4, or transforming growth factor beta (TGF
      beta). We fed transgenic animals a low-dose (1 mg x 5) or high-dose (25 mg x 1)
      regimen of mouse MBP and without further immunization spleen cells were tested
      for cytokine production. Low-dose feeding induced prominent secretion of IL-4, IL
      10, and TGF-beta, whereas minimal secretion of these cytokines was observed with
      high-dose feeding. Little or no change was seen in proliferation or IL-2/IFN
      gamma secretion in fed animals irrespective of the dose. To demonstrate in vivo
      functional activity of the cytokine-secreting cells generated by oral antigen,
      spleen cells from low-dose-fed animals were adoptively transferred into naive
      (PLJ x SJL)F1 mice that were then immunized for the development of experimental
      autoimmune encephalomyelitis (EAE). Marked suppression of EAE was observed when T
      cells were transferred from MBP-fed transgenic animals but not from animals that
      were not fed. In contrast to oral tolerization, s.c. immunization of transgenic
      animals with MBP in complete Freund's adjuvant induced IFN-gamma-secreting Th1
      cells in vitro and experimental encephalomyelitis in vivo. Despite the large
      number of cells reactive to MBP in the transgenic animals, EAE was also
      suppressed by low-dose feeding of MBP prior to immunization. These results
      demonstrate that MBP-specific T cells can differentiate in vivo into
      encephalitogenic or regulatory T cells depending upon the context by which they
      are exposed to antigen.

PMID- 8552645
TI  - Molecular cloning of a protein kinase whose phosphorylation is regulated by
      genetic adhesion during Chlamydomonas fertilization.
AB  - Fertilization in Chlamydomonas is initiated by adhesive interactions between
      gametes of opposite mating types through flagellar glycoproteins called
      agglutinins. Interactions between these cell adhesion molecules signal for the
      activation of adenylyl cyclase through an interplay of protein kinases and
      ultimately result in formation of a diploid zygote. One of the early events
      during adhesion-induced signal transduction is the rapid inactivation of a
      flagellar protein kinase that phosphorylates a 48-kDa protein in the flagella. We
      report the biochemical and molecular characterization of the 48-kDa protein.
      Experiments using a bacterially expressed fusion protein show that the 48-kDa
      protein is capable of autophosphorylation on serine and tyrosine and
      phosphorylation of bovine beta-casein on serine, confirming that the 48-kDa
      protein itself has protein kinase activity. This protein kinase exhibits limited
      homology to members of the eukaryotic protein kinase superfamily and may be an
      important element in a signaling pathway in fertilization.

PMID- 8552646
TI  - X-ray structure of a vanadium-containing enzyme: chloroperoxidase from the fungus
      Curvularia inaequalis.
AB  - The chloroperoxidase (EC 1.11.1.-) from the fungus Curvularia inaequalis belongs
      to a class of vanadium enzymes that oxidize halides in the presence of hydrogen
      peroxide to the corresponding hypohalous acids. The 2.1 A crystal structure (R =
      20%) of an azide chloroperoxidase complex reveals the geometry of the catalytic
      vanadium center. Azide coordinates directly to the metal center, resulting in a
      structure with azide, three nonprotein oxygens, and a histidine as ligands. In
      the native state vanadium will be bound as hydrogen vanadate(V) in a trigonal
      bipyramidal coordination with the metal coordinated to three oxygens in the
      equatorial plane, to the OH group at one apical position, and to the epsilon 2
      nitrogen of a histidine at the other apical position. The protein fold is mainly
      alpha-helical with two four-helix bundles as main structural motifs and an
      overall structure different from other structures. The helices pack together to a
      compact molecule, which explains the high stability of the protein. An amino acid
      sequence comparison with vanadium-containing bromoperoxidase from the seaweed
      Ascophyllum nodosum shows high similarities in the regions of the metal binding
      site, with all hydrogen vanadate(V) interacting residues conserved except for
      lysine-353, which is an asparagine.

PMID- 8552647
TI  - Smoothness within ruggedness: the role of neutrality in adaptation.
AB  - RNA secondary structure folding algorithms predict the existence of connected
      networks of RNA sequences with identical structure. On such networks, evolving
      populations split into subpopulations, which diffuse independently in sequence
      space. This demands a distinction between two mutation thresholds: one at which
      genotypic information is lost and one at which phenotypic information is lost. In
      between, diffusion enables the search of vast areas in genotype space while still
      preserving the dominant phenotype. By this dynamic the success of phenotypic
      adaptation becomes much less sensitive to the initial conditions in genotype
      space.

PMID- 8552648
TI  - Suppression of experimental arthritis by gene transfer of interleukin 1 receptor
      antagonist cDNA.
AB  - Restoration of the impaired balance between pro- and antiinflammatory cytokines
      should provide effective treatment of rheumatoid arthritis. Gene therapy has been
      proposed as an approach for delivery of therapeutic proteins to arthritic joints.
      Here, we examined the efficacy of antiinflammatory gene therapy in bacterial cell
      wall-induced arthritis in rats. Human secreted interleukin 1 receptor antagonist
      (sIL-1ra) was expressed in joints of rats with recurrent bacterial cell wall
      induced arthritis by using ex vivo gene transfer. To achieve this, primary
      synoviocytes were transduced in culture with a retroviral vector carrying the sIL
      1ra cDNA. Transduced cells were engrafted in ankle joints of animals prior to
      reactivation of arthritis. Animals in control groups were engrafted with
      synoviocytes transduced with lacZ and neo marker genes. Cells continued to
      express transferred genes for at least 9 days after engraftment. We found that
      gene transfer of sIL-1ra significantly suppressed the severity of recurrence of
      arthritis, as assessed by measuring joint swelling and by the gross-observation
      score, and attenuated but did not abolish erosion of cartilage and bone. The
      effect of intraarticularly expressed sIL-1ra was essentially local, as there was
      no significant difference in severity of recurrence between unengrafted
      contralateral joints in control and experimental groups. We estimate that locally
      expressed sIL-1ra was about four orders of magnitude more therapeutically
      efficient than systemically administered recombinant sIL-1ra protein. These
      findings provide experimental evidence for the feasibility of antiinflammatory
      gene therapy for arthritis.

PMID- 8552649
TI  - Targeted disruption of gp130, a common signal transducer for the interleukin 6
      family of cytokines, leads to myocardial and hematological disorders.
AB  - gp130 is a ubiquitously expressed signal-transducing receptor component shared by
      interleukin 6, interleukin 11, leukemia inhibitory factor, oncostatin M, ciliary
      neurotrophic factor, and cardiotrophin 1. To investigate physiological roles of
      gp130 and to examine pathological consequences of a lack of gp130, mice deficient
      for gp130 have been prepared. Embryos homozygous for the gp130 mutation
      progressively die between 12.5 days postcoitum and term. On 16.5 days postcoitum
      and later, they show hypoplastic ventricular myocardium without septal and
      trabecular defect. The subcellular ultrastructures in gp130-/- cardiomyocytes
      appear normal. The mutant embryos have greatly reduced numbers of pluripotential
      and committed hematopoietic progenitors in the liver and differentiated lineages
      such as T cells in the thymus. Some gp130-/- embryos show anemia due to impaired
      development of erythroid lineage cells. These results indicate that gp130 plays a
      crucial role in myocardial development and hematopoiesis during embryogenesis.

PMID- 8552650
TI  - Isolation of an ovine pulmonary surfactant-associated anionic peptide
      bactericidal for Pasteurella haemolytica.
AB  - Ovine pulmonary surfactant is bactericidal for Pasteurella haemolytica when
      surfactant and bacteria mixtures are incubated with normal ovine serum. To
      isolate this component, surfactant (1 mg/ml) was centrifuged at 100,000 x gav,
      and the supernatant was fractionated by HPLC. Fractions were eluted with
      acetonitrile (10-100%)/0.1% trifluoracetic acid and tested for bactericidal
      activity. Amino acid and sequence analysis of three bactericidal fractions showed
      that fraction 2 contained H-GDDDDDD-OH, fraction 3 contained H-DDDDDDD-OH, and
      fraction 6 contained H-GADDDDD-OH. Peptides in 0.14 M NaCl/10 microM ZnCl2 (zinc
      saline solution) induced killing of P. haemolytica and other bacteria comparable
      to defensins and beta-defensins [minimal bactericidal concentration (MBC)50
      range, 0.01-0.06 mM] but not in 0.14 M NaCl/10 mM sodium phosphate buffer, pH
      7.2/0.5 mM CaCl2/0.15 mM MgCl2 (MBC50 range, 2.8-11.5 mM). Bactericidal activity
      resided in the core aspartate hexapeptide homopolymeric region, and MBC50 values
      of aspartate dipeptide-to-heptapeptide homopolymers were inversely proportional
      to the number of aspartate residues in the peptide. P. haemolytica incubated with
      H-DDDDDD-OH in zinc saline solution was killed within 30 min. Ultrastructurally,
      cells contained flocculated intracellular constituents. In contrast to cationic
      defensins and beta-defensins, surfactant-associated anionic peptides are smaller
      in size, opposite in charge, and are bactericidal in zinc saline solution. They
      are members of another class of peptide antibiotics containing aspartate, which
      when present in pulmonary secretions may help clear bacteria as a part of the
      innate pulmonary defense system.

PMID- 8552651
TI  - Codon repeats in genes associated with human diseases: fewer repeats in the genes
      of nonhuman primates and nucleotide substitutions concentrated at the sites of
      reiteration.
AB  - Five human diseases are due to an excessive number of CAG repeats in the coding
      regions of five different genes. We have analyzed the repeat regions in four of
      these genes from nonhuman primates, which are not known to suffer from the
      diseases. These primates have CAG repeats at the same sites as in human alleles,
      and there is similar polymorphism of repeat number, but this number is smaller
      than in the human genes. In some of the genes, the segment of poly(CAG) has
      expanded in nonhuman primates, but the process has advanced further in the human
      lineage than in other primate lineages, thereby predisposing to diseases of CAG
      reiteration. Adjacent to stretches of homogeneous present-day codon repeats,
      previously existing codons of the same kind have undergone nucleotide
      substitutions with high frequency. Where these lead to amino acid substitutions,
      the effect will be to reduce the length of the original homopolymeric stretch in
      the protein.

PMID- 8552652
TI  - Single neuron control over a complex motor program.
AB  - While there are many instances of single neurons that can drive rhythmic stimulus
      elicited motor programs, such neurons have seldom been found to be necessary for
      motor program function. In the isolated central nervous system of the marine
      mollusc Tritonia diomedea, brief stimulation (1 sec) of a peripheral nerve
      activates an interneuronal central pattern generator that produces the long
      lasting (approximately 30-60 sec) motor program underlying the animal's rhythmic
      escape swim. Here, we identify a single interneuron, DRI (for dorsal ramp
      interneuron), that (i) conveys the sensory information from this stimulus to the
      swim central pattern generator, (ii) elicits the swim motor program when driven
      with intracellular stimulation, and (iii) blocks the depolarizing "ramp" input to
      the central pattern generator, and consequently the motor program itself, when
      hyperpolarized during the nerve stimulus. Because most of the sensory information
      appears to be funneled through this one neuron as it enters the pattern
      generator, DRI presents a striking example of single neuron control over a
      complex motor circuit.

PMID- 8552654
TI  - The peptide binding site of the substance P (NK-1) receptor localized by a
      photoreactive analogue of substance P: presence of a disulfide bond.
AB  - Substance P (SP) is a neuropeptide that mediates multiple physiological responses
      including transmission of painful stimuli and inflammation via an interaction
      with a receptor of known primary sequence. To identify the regions of the SP
      receptor, also termed the NK-1 receptor, involved in peptide recognition, we are
      using analogues of SP containing the photoreactive amino acid p-benzoyl-L
      phenylalanine (Bpa). In the present study, we used radioiodinated Bpa8-SP to
      covalently label with high efficiency the rat SP receptor expressed in a
      transfected mammalian cell line. To identify the amino acid residue that serves
      as the site of covalent attachment, a membrane preparation of labeled receptor
      was subjected to partial enzymatic cleavage by trypsin. A major digestion product
      of 22 kDa was identified. Upon reduction with 2-mercaptoethanol the mass of this
      product decreased to 14 kDa. The 22-kDa tryptic fragment was purified in
      excellent yield by preparative SDS/PAGE under nonreducing conditions. Subcleavage
      with Staphylococcus aureus V8 protease and endoproteinase ArgC yielded fragments
      of 8.2 and 9.0 kDa, respectively. Upon reductive cleavage, the V8 protease
      fragment decreased to 3.0 kDa while the endoproteinase ArgC fragment decreased to
      3.2 kDa. Taking into consideration enzyme specificity, molecular size,
      determination of the presence or absence of N-glycosylation sites, and
      recognition by antibodies to specific sequences of the SP receptor, the V8
      protease fragment is Thr-173 to Glu-183, while the endoproteinase ArgC fragment
      is Val-178 to Arg-190. These two fragments share the common sequence Val-Val-Cys
      Met-Ile-Glu (residues 178-183). The site of covalent attachment of radioiodinated
      Bpa8-SP is thus restricted to a residue within this overlap sequence. The data
      presented here also establish that the cysteine residue in this sequence Cys-180,
      which is positioned in the middle of the second extracellular loop, participates
      in a disulfide bond that links the first and second extracellular loops of the
      receptor.

PMID- 8552655
TI  - Structure-activity relationships derived by machine learning: the use of atoms
      and their bond connectivities to predict mutagenicity by inductive logic
      programming.
AB  - We present a general approach to forming structure-activity relationships (SARs).
      This approach is based on representing chemical structure by atoms and their bond
      connectivities in combination with the inductive logic programming (ILP)
      algorithm PROGOL. Existing SAR methods describe chemical structure by using
      attributes which are general properties of an object. It is not possible to map
      chemical structure directly to attribute-based descriptions, as such descriptions
      have no internal organization. A more natural and general way to describe
      chemical structure is to use a relational description, where the internal
      construction of the description maps that of the object described. Our atom and
      bond connectivities representation is a relational description. ILP algorithms
      can form SARs with relational descriptions. We have tested the relational
      approach by investigating the SARs of 230 aromatic and heteroaromatic nitro
      compounds. These compounds had been split previously into two subsets, 188
      compounds that were amenable to regression and 42 that were not. For the 188
      compounds, a SAR was found that was as accurate as the best statistical or neural
      network-generated SARs. The PROGOL SAR has the advantages that it did not need
      the use of any indicator variables handcrafted by an expert, and the generated
      rules were easily comprehensible. For the 42 compounds, PROGOL formed a SAR that
      was significantly (P < 0.025) more accurate than linear regression, quadratic
      regression, and back-propagation. This SAR is based on an automatically generated
      structural alert for mutagenicity.

PMID- 8552653
TI  - Neuroprotective strategy for Alzheimer disease: intranasal administration of a
      fatty neuropeptide.
AB  - Neurodegenerative diseases, in which neuronal cell disintegrate, bring about
      deteriorations in cognitive functions as is evidenced in millions of Alzheimer
      patients. A major neuropeptide, vasoactive intestinal peptide (VIP), has been
      shown to be neuroprotective and to play an important role in the acquisition of
      learning and memory. A potent lipophilic analogue to VIP now has been
      synthesized, [stearyl-norleucine17]VIP ([St-Nle17]VIP), that exhibited
      neuroprotection in model systems related to Alzheimer disease. The beta-amyloid
      peptide is a major component of the cerebral amyloid plaque in Alzheimer disease
      and has been shown to be neurotoxic. We have found a 70% loss in the number of
      neurons in rat cerebral cortical cultures treated with the beta-amyloid peptide
      (amino acids 25-35) in comparison to controls. This cell death was completely
      prevented by cotreatment with 0.1 pM [St-Nle17]VIP. Furthermore, characteristic
      deficiencies in Alzheimer disease result from death of cholinergic neurons. Rats
      treated with a cholinergic blocker (ethylcholine aziridium) have been used as a
      model for cholinergic deficits. St-Nle-VIP injected intracerebroventricularly or
      delivered intranasally prevented impairments in spatial learning and memory
      associated with cholinergic blockade. These studies suggest both an unusual
      therapeutic strategy for treatment of Alzheimer deficiencies and a means for
      noninvasive peptide administration to the brain.

PMID- 8552656
TI  - Determining RNA solution structure by segmental isotopic labeling and NMR:
      application to Caenorhabditis elegans spliced leader RNA 1.
AB  - Recent developments in multidimensional heteronuclear NMR spectroscopy and large
      scale synthesis of uniformly 13C- and 15N-labeled oligonucleotides have greatly
      improved the prospects for determination of the solution structure of RNA.
      However, there are circumstances in which it may be advantageous to label only a
      segment of the entire RNA chain. For example, in a larger RNA molecule the
      structural question of interest may reside in a localized domain. Labeling only
      the corresponding nucleotides simplifies the spectrum and resonance assignments
      because one can filter proton spectra for coupling to 13C and 15N. Another
      example is in resolving alternative secondary structure models that are
      indistinguishable in imino proton connectivities. Here we report a general method
      for enzymatic synthesis of quantities of segmentally labeled RNA molecules
      required for NMR spectroscopy. We use the method to distinguish definitively two
      competing secondary structure models for the 5' half of Caenorhabditis elegans
      spliced leader RNA by comparison of the two-dimensional [15N] 1H heteronuclear
      multiple quantum correlation spectrum of the uniformly labeled sample with that
      of a segmentally labeled sample. The method requires relatively small samples;
      solutions in the 200-300 microM concentration range, with a total of 30 nmol or
      approximately 40 micrograms of RNA in approximately 150 microliters, give strong
      NMR signals in a short accumulation time. The method can be adapted to label an
      internal segment of a larger RNA chain for study of localized structural
      problems. This definitive approach provides an alternative to the more common
      enzymatic and chemical footprinting methods for determination of RNA secondary
      structure.

PMID- 8552657
TI  - Myosin dynamics in live Dictyostelium cells.
AB  - Conventional myosin plays a key role in the cytoskeletal reorganization necessary
      for cytokinesis, migration, and morphological changes associated with development
      in nonmuscle cells. We have made a fusion between the green fluorescent protein
      (GFP) and the Dictyostelium discoideum myosin heavy chain (GFP-myosin). The
      unique Dictyostelium system allows us to test the GFP-tagged myosin for activity
      both in vivo and in vitro. Expression of GFP-myosin rescues all myosin null cell
      defects. Additionally, GFP-myosin purified from these cells exhibits the same
      ATPase activities and in vitro motility as wild-type myosin. GFP-myosin is
      concentrated in the cleavage furrow during cytokinesis and in the posterior
      cortex of migrating cells. Surprisingly, GFP-myosin concentration increases
      transiently in the tips of retracting pseudopods. Contrary to previous thinking,
      this suggests that conventional myosin may play an important role in the dynamics
      of pseudopods as well as filopodia, lamellipodia, and other cellular protrusions.

PMID- 8552658
TI  - The Drosophila melanogaster dodo (dod) gene, conserved in humans, is functionally
      interchangeable with the ESS1 cell division gene of Saccharomyces cerevisiae.
AB  - We have sequenced the region of DNA adjacent to and including the flightless
      (fli) gene of Drosophila melanogaster and molecularly characterized four
      transcription units within it, which we have named tweety (twe), flightless
      (fli), dodo (dod), and penguin (pen). We have performed deletion and transgenic
      analysis to determine the consequences of the quadruple gene removal. Only the
      flightless gene is vital to the organism; the simultaneous absence of the other
      three allows the overriding majority of individuals to develop to adulthood and
      to fly normally. These gene deletion results are evaluated in the context of the
      redundancy and degeneracy inherent in many genetic networks. Our cDNA analyses
      and data-base searches reveal that the predicted dodo protein has homologs in
      other eukaryotes and that it is made up of two different domains. The first,
      designated WW, is involved in protein-protein interactions and is found in
      functionally diverse proteins including human dystrophin. The second is involved
      in accelerating protein folding and unfolding and is found in Escherichia coli in
      a new family of peptidylprolyl cis-trans isomerases (PPIases; EC 5.2.1.8). In
      eukaryotes, PPIases occur in the nucleus and the cytoplasm and can form stable
      associations with transcription factors, receptors, and kinases. Given this
      particular combination of domains, the dodo protein may well participate in a
      multisubunit complex involved in the folding and activation of signaling
      molecules. When we expressed the dodo gene product in Saccharomyces cerevisiae,
      it rescued the lethal phenotype of the ESS1 cell division gene.

PMID- 8552659
TI  - Monoclonal antibodies inhibit in vitro fibrillar aggregation of the Alzheimer
      beta-amyloid peptide.
AB  - The beta-amyloid peptide, the hallmark of Alzheimer disease, forms fibrillar
      toxic aggregates in brain tissue that can be dissolved only by strong denaturing
      agents. To study beta-amyloid formation and its inhibition, we prepared immune
      complexes with two monoclonal antibodies (mAbs), AMY-33 and 6F/3D, raised against
      beta-amyloid fragments spanning amino acid residues 1-28 and 8-17 of the beta
      amyloid peptide chain, respectively. In vitro aggregation of beta-amyloid peptide
      was induced by incubation for 3 h at 37 degrees C and monitored by ELISA,
      negative staining electron microscopy, and fluorimetric studies. We found that
      the mAs prevent the aggregation of beta-amyloid peptide and that the inhibitory
      effect appears to be related to the localization of the antibody-binding sites
      and the nature of the aggregating agents. Preparation of mAbs against
      "aggregating epitopes," defined as sequences related to the sites where protein
      aggregation is initiated, may lead to the understanding and prevention of protein
      aggregation. The results of this study may provide a foundation for using mAbs in
      vivo to prevent the beta-amyloid peptide aggregation that is associated with
      Alzheimer disease.

PMID- 8552660
TI  - Differential toxicity of mitomycin C and porfiromycin to aerobic and hypoxic
      Chinese hamster ovary cells overexpressing human NADPH:cytochrome c (P-450)
      reductase.
AB  - Purified NADPH:cytochrome c (P-450) reductase (FpT; NADPH-ferrihemoprotein
      oxidoreductase, EC 1.6.2.4) can reductively activate mitomycin antibiotics
      through a one-electron reduction to species that alkylate DNA. To assess the
      involvement of FpT in the intracellular activation of the mitomycins,
      transfectants overexpressing a human FpT cDNA were established from a Chinese
      hamster ovary cell line deficient in dihydrofolate reductase (CHO-K1/dhfr-). The
      parental cell line was equisensitive to the cytotoxic action of mitomycin C under
      oxygenated and hypoxic conditions. In contrast, porfiromycin was considerably
      less cytotoxic to wild-type parental cells than was mitomycin C in air and
      markedly more cytotoxic under hypoxia. Two FpT-transfected clones were selected
      that expressed 19- and 27-fold more FpT activity than the parental line. Levels
      of other oxidoreductases implicated in the activation of the mitomycins were
      unchanged. Significant increases in sensitivity to mitomycin C and porfiromycin
      in the two FpT-transfected clones were seen under both oxygenated and hypoxic
      conditions, with the increases in toxicity being greater under hypoxia than in
      air. These findings demonstrate that FpT can bioreductively activate the
      mitomycins in living cells and implicate FpT in the differential aerobic/hypoxic
      toxicity of the mitomycins.

PMID- 8552661
TI  - Construction and characterization of an azurin analog for the purple copper site
      in cytochrome c oxidase.
AB  - A protein analog of a purple copper center has been constructed from a
      recombinant blue copper protein (Pseudomonas aeruginosa azurin) by replacing the
      loop containing the three ligands to the blue copper center with the
      corresponding loop of the CuA center in cytochrome c oxidase (COX) from
      Paracoccus denitrificans. The electronic absorption in the UV and visible region
      (UV-vis) and electron paramagnetic resonance (EPR) spectra of this analog are
      remarkably similar to those of the native CuA center in COX from Paracoccus
      denitrificans. The above spectra can be obtained upon addition of a mixture of
      Cu2+ and Cu+. Addition of Cu2+ only results in a UV-vis spectrum consisting of
      absorptions from both a purple copper center and a blue copper center. This
      spectrum can be converted to the spectrum of a pure purple copper by a prolonged
      incubation in the air, or by addition of excess ascorbate. The azurin mutant
      reported here is an example of an engineered purple copper center with the
      A480/A530 ratio greater than 1 and with no detectable hyperfines, similar to
      those of the CuA sites in COX of bovine heart and of Paracoccus denitrificans.

PMID- 8552662
TI  - Retinoblastoma protein directly interacts with and activates the transcription
      factor NF-IL6.
AB  - The biological function of the retinoblastoma protein (RB) in the cell division
      cycle has been extensively documented, but its apparent role in differentiation
      remains largely unexplored. To investigate how RB is involved in differentiation,
      the U937 large-cell lymphoma line was induced to differentiate along a
      monocyte/macrophage lineage. During differentiation RB was found to interact
      directly through its simian virus 40 large tumor antigen (T antigen)-binding
      domain with NF-IL6, a member of the CAAT/enhancer-binding protein (C/EBP) family
      of transcription factors. NF-IL6 utilizes two distinct regions to bind to the
      hypophosphorylated form of RB in vitro and in cells. Wild-type but not mutant RB
      enhanced both binding activity of NF-IL6 to its cognate DNA sequences in vitro
      and promoter transactivation by NF-IL6 in cells. These findings indicate a novel
      biochemical function of RB: it activates, by an apparent chaperone-like activity,
      specific transcription factors important for differentiation. This contrasts with
      its sequestration and inactivation of other transcription factors, such as E2F-1,
      which promote progression of the cell cycle. Such disparate mechanisms may help
      to explain the dual role of RB in cell differentiation and the cell division
      cycle.

PMID- 8552663
TI  - Selective repression of transcriptional activators by Pbx1 does not require the
      homeodomain.
AB  - PBX1 is a homeobox-containing gene identified as the chromosome 1 participant of
      the t(1;19) chromosomal translocation of childhood pre-B-cell acute lymphoblastic
      leukemia. This translocation produces a fusion gene encoding the chimeric
      oncoprotein E2A-Pbx1, which can induce both acute myeloid and T-lymphoid leukemia
      in mice. The binding of Pbx1 to DNA is weak; however, both Pbx1 and E2A-Pbx1
      exhibit tight binding to specific DNA motifs in conjunction with certain other
      homeodomain proteins, and E2A-Pbx1 activates transcription through these motifs,
      whereas Pbx1 does not. In this report, we investigate potential transcriptional
      functions of Pbx1, using transient expression assays. While no segments of Pbx1
      activated transcription, an internal domain of Pbx1 repressed transcription
      induced by the activation domain of Sp1, but not by the activation domains of
      VP16 or p53. This Pbx1 domain, which lies upstream of the homeodomain and is
      highly conserved among Pbx proteins, is thus predicted to bind a specific
      transcription factor. Surprisingly, the repression activity of Pbx1 did not
      require homeodomain-dependent DNA binding. Thus, Pbx1 may be able to alter gene
      transcription by both DNA-binding-dependent and DNA-binding-independent
      mechanisms.

PMID- 8552664
TI  - Activation of single whisker barrel in rat brain localized by functional magnetic
      resonance imaging.
AB  - The previously established cortical representation of rat whiskers in layer IV of
      the cortex contains distinct cylindrical columns of cellular aggregates, which
      are termed barrels and correlate in a one-to-one relation to whiskers on the
      contralateral rat face. In the present study, functional magnetic resonance
      imaging (fMRI) of the rat brain was used to map whisker barrel activation during
      mechanical up-down movement (+/- 2.5 mm amplitude at 8 Hz) of single/multiple
      whisker(s). Multislice gradient echo fMRI experiments were performed at 7 T with
      in-plane image resolution of 220 x 220 microns, slice thickness of 1 mm, and echo
      time of 16 ms. Highly significant (P < 0.001) and localized contralateral regions
      of activation were observed upon stimulation of single/multiple whisker(s). In
      all experiments (n = 10), the locations of activation relative to bregma and
      midline were highly correlated with the neuroanatomical position of the
      corresponding whisker barrels, and the results were reproducible intra- and
      interanimal. Our results indicate that fMRI based on blood oxygenation level
      dependent image contrast has the sensitivity to depict activation of a single
      whisker barrel in the rat brain. This noninvasive technique will supplement
      existing methods in the study of rat barrel cortex and should be particularly
      useful for the long-term investigations of central nervous system in the same
      animal.

PMID- 8552665
TI  - Gain of chromosome 3q defines the transition from severe dysplasia to invasive
      carcinoma of the uterine cervix.
AB  - We have chosen tumors of the uterine cervix as a model system to identify
      chromosomal aberrations that occur during carcinogenesis. A phenotype/genotype
      correlation was established in defined regions of archived, formalin-fixed, and
      hematoxylin/eosin-stained tissue sections that were dissected from normal
      cervical epithelium (n = 3), from mild (n = 4), moderate (n = 6), and severe
      dysplasias/carcinomas in situ (CIS) (n = 13), and from invasive carcinomas (n =
      10) and investigated by comparative genomic hybridization. The same tissues were
      analyzed for DNA ploidy, proliferative activity, and the presence of human
      papillomavirus (HPV) sequences. The results show that an increase in
      proliferative activity and tetraploidization had occurred already in mildly
      dysplastic lesions. No recurrent chromosomal aberrations were observed in DNA
      extracted from normal epithelium or from mild and moderate dysplasias, indicating
      that the tetraploidization precedes the loss or gain of specific chromosomes. A
      gain of chromosome 3q became visible in one of the severe dysplasias/CIS.
      Notably, chromosome 3q was overrepresented in 90% of the carcinomas and was also
      found to have undergone a high-level copy-number increase (amplification). We
      therefore conclude that the gain of chromosome 3q that occurs in HPV16-infected,
      aneuploid cells represents a pivotal genetic aberration at the transition from
      severe dysplasia/CIS to invasive cervical carcinoma.

PMID- 8552666
TI  - Longevity and the genetic determination of collagen glycoxidation kinetics in
      mammalian senescence.
AB  - A fundamental question in the basic biology of aging is whether there is a
      universal aging process. If indeed such a process exists, one would expect that
      it develops at a higher rate in short- versus long-lived species. We have
      quantitated pentosidine, a marker of glycoxidative stress in skin collagen from
      eight mammalian species as a function of age. A curvilinear increase was modeled
      for all species, and the rate of increase correlated inversely with maximum life
      span. Dietary restriction, a potent intervention associated with increased life
      span, markedly inhibited glycoxidation rate in the rodent. On the assumption that
      collagen turnover rate is primarily influenced by the crosslinking due to
      glycoxidation, these results suggest that there is a progressive age-related
      deterioration of the process that controls the collagen glycoxidation rate. Thus,
      the ability to withstand damage due to glycoxidation and the Maillard reaction
      may be under genetic control.

PMID- 8552667
TI  - Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon
      precursors in human infants.
AB  - It is becoming clear that an adequate level of long-chain highly unsaturated
      fatty acids in the nervous system is required for optimal function and
      development; however, the ability of infants to biosynthesize long-chain fatty
      acids is unknown. This study explores the capacity of human infants to convert 18
      carbon essential fatty acids to their elongated and desaturated forms, in vivo. A
      newly developed gas chromatography/negative chemical ionization/mass spectrometry
      method employing 2H-labeled essential fatty acids allowed assessment of this in
      vivo conversion with very high sensitivity and selectivity. Our results
      demonstrate that human infants have the capacity to convert dietary essential
      fatty acids administered enterally as 2H-labeled ethyl esters to their longer
      chain derivatives, transport them to plasma, and incorporate them into membrane
      lipids. The in vivo conversion of linoleic acid (18:2n6) to arachidonic acid
      (20:4n6) is demonstrated in human beings. All elongases/desaturases necessary for
      the conversion of linolenic acid (18:3n3) to docosahexaenoic acid (22:6n3) are
      also active in the first week after birth. Although the absolute amounts of n-3
      fatty acid metabolites accumulated in plasma are greater than those of the n-6
      family, estimates of the endogenous pools of 18:2n6 and 18:3n3 indicate that n-6
      fatty acid conversion rates are greater than those of the n-3 family. While these
      data clearly demonstrate the capability of infants to biosynthesize 22:6n3, a
      lipid that is required for optimal neural development, the amounts produced in
      vivo from 18:3n3 may be inadequate to support the 22:6n3 level observed in breast
      fed infants.

PMID- 8552668
TI  - Specific cloning of human DNA as yeast artificial chromosomes by transformation
      associated recombination.
AB  - DNA molecules undergoing transformation into yeast are highly recombinogenic,
      even when diverged. We reasoned that transformation-associated recombination
      (TAR) could be employed to clone large DNAs containing repeat sequences, thereby
      eliminating the need for in vitro enzymatic reactions such as restriction and
      ligation and reducing the amount of DNA handling. Gently isolated human DNA was
      transformed directly into yeast spheroplasts along with two genetically marked
      (M1 and M2) linearized vectors that contained a human Alu sequence at one end and
      a telomere sequence at the other end (Alu-CEN-M1-TEL and Alu-M2-TEL). Nearly all
      the M1-selected transformants had yeast artificial chromosomes (YACs) containing
      human DNA inserts that varied in size from 70 kb to > 600 kb. Approximately half
      of these had also acquired the unselected M2 marker. The mitotic segregational
      stability of YACs generated from one (M1) or two (M1 and M2) vector(s) was
      comparable, suggesting de novo generation of telomeric ends. Since no YACs were
      isolated when rodent DNAs or a vector lacking an Alu sequence was used, the YACs
      were most likely the consequence of TAR between the repeat elements on the
      vector(s) and the human DNA. Using the BLUR13 Alu-containing vector, we
      demonstrated that human DNA could be efficiently cloned from mouse cells that
      contained a single human chromosome 16. The distribution of cloned DNAs on
      chromosome 16 was determined by fluorescence in situ hybridization. We propose
      that TAR cloning can provide an efficient means for generating YACs from specific
      chromosomes and subchromosome fragments and that TAR cloning may be useful for
      isolating families of genes and specific genes from total genome DNA.

PMID- 8552669
TI  - Cloning and characterization of a binding subunit of the interleukin 13 receptor
      that is also a component of the interleukin 4 receptor.
AB  - Interleukins 4 (IL-4) and 13 (IL-13) have been found previously to share receptor
      components on some cells, as revealed by receptor cross-competition studies. In
      the present study, the cloning is described of murine NR4, a previously
      unrecognized receptor identified on the basis of sequence similarity with members
      of the hemopoietin receptor family. mRNA encoding NR4 was found in a wide range
      of murine cells and tissues. By using transient expression in COS-7 cells, NR4
      was found to encode the IL-13 receptor alpha chain, a low-affinity receptor
      capable of binding IL-13 but not IL-4 or interleukins 2, -7, -9, or -15. Stable
      expression of the IL-13 receptor alpha chain (NR4) in CTLL-2 cells resulted in
      the generation of high-affinity IL-13 receptors capable of transducing a
      proliferative signal in response to IL-13 and, moreover, led to competitive cross
      reactivity in the binding of IL-4 and IL-13. These results suggest that the IL-13
      receptor alpha chain (NR4) is the primary binding subunit of the IL-13 receptor
      and may also be a component of IL-4 receptors.

PMID- 8552670
TI  - Identification, purification, and molecular cloning of autonomously replicating
      sequence-binding protein 1 from fission yeast Schizosaccharomyces pombe.
AB  - Autonomously replicating sequence (ARS) elements of the fission yeast
      Schizosaccharomyces pombe contain multiple imperfect copies of the consensus
      sequence reported by Maundrell et al. [Maundrell K., Hutchison, A. & Shall, S.
      (1988) EMBO J. 7, 2203-2209]. When cell free extracts of S. pombe were incubated
      with a dimer or tetramer of an oligonucleotide containing the ARS consensus
      sequence, several complexes were detected using a gel mobility-shift assay. The
      proteins forming these complexes also bind ars3002, which is the most active
      origin in the ura4 region of chromosome III of S. pombe. One protein, partly
      responsible for the binding activity observed with crude extracts, was purified
      to near homogeneity. It is a 60-kDa protein and was named ARS-binding protein 1
      (Abp1). Abp1 preferentially binds to multiple sites in ARS 3002 and to the DNA
      polymer poly[d(A.T)]. The cloning and sequence of the gene coding for Abp1
      revealed that it encodes a protein of 59.8 kDa (522 amino acids). Abp1 has
      significant homology (25% identity, 50% similarity) to the N-terminal region
      (approximately 300 amino acids) of the human and mouse centromere DNA-binding
      protein CENP-B. Because centromeres of S. pombe contain a high density of ARS
      elements, Abp1 may play a role connecting DNA replication and chromosome
      segregation.

PMID- 8552671
TI  - In vitro activation of the interferon-induced, double-stranded RNA-dependent
      protein kinase PKR by RNA from the 3' untranslated regions of human alpha
      tropomyosin.
AB  - The cellular kinase known as PKR (protein kinase RNA-activated) is induced by
      interferon and activated by RNA. PKR is known to have antiviral properties due to
      its role in translational control. Active PKR phosphorylates eukaryotic
      initiation factor 2 alpha and leads to inhibition of translation, including viral
      translation. PKR is also known to function as a tumor suppressor, presumably by
      limiting the rate of tumor-cell translation and growth. Recent research has shown
      that RNA from the 3' untranslated region (3'UTR) of human alpha-tropomyosin has
      tumor-suppressor properties in vivo [Rastinejad, F., Conboy, M. J., Rando, T. A.
      & Blau, H. M. (1993) Cell 75, 1107-1117]. Here we report that purified RNA from
      the 3'UTR of human alpha-tropomyosin can inhibit in vitro translation in a manner
      consistent with activation of PKR. Inhibition of translation by tropomyosin 3'UTR
      RNA was observed in a rabbit reticulocyte lysate system, which is known to
      contain endogenous PKR but was not seen in wheat germ lysate, which is not
      responsive to a known activator of PKR. A control RNA purified in the same manner
      as the 3'UTR RNA did not inhibit translation in either system. The inhibition of
      translation observed in reticulocyte lysates was prevented by the addition of
      adenovirus virus-associated RNA1 (VA RNAI), an inhibitor of PKR activation.
      Tropomyosin 3'UTR RNA was bound by immunoprecipitated PKR and activated the
      enzyme in an in vitro kinase assay. These data suggest that activation of PKR
      could be the mechanism by which tropomyosin 3'UTR RNA exerts its tumor
      suppression activity in vivo.

PMID- 8552672
TI  - Inhibition of Plasmodium falciparum malaria using antisense
      oligodeoxynucleotides.
AB  - We studied inhibition of growth of the malaria parasite Plasmodium falciparum in
      in vitro culture using antisense (AS) oligodeoxynucleotides (ODNs) against
      different target genes. W2 and W2mef strains of drug-resistant parasites were
      exposed to AS ODNs over 48 hr, and growth was determined by microscopic
      examination and [3H]hypoxanthine incorporation. At ODN concentrations of 1
      microM, phosphorothioate (PS) ODNs inhibited growth in a target-independent
      manner. However, between 0.5 and 0.005 microM, ODNs against dihydrofolate
      reductase, dihydropteroate synthetase, ribonucleotide reductase, the schizont
      multigene family, and erythrocyte binding antigen EBA175 significantly inhibited
      growth compared with a PS AS ODN against human immunodeficiency virus, two AS
      ODNs containing eight mismatches, or the sense strand controls (P < 0.0001). The
      IC50 was approximately 0.05 microM, whereas that for non-sequence-specific
      controls was 15-fold higher. PS AS ODNs against DNA polymerase alpha showed less
      activity than that for other targets, whereas a single AS ODN against triose
      phosphate isomerase did not differ significantly from controls. We conclude that
      at concentrations below 0.5 microM, PS AS ODNs targeted against several malarial
      genes significantly inhibit growth of drug-resistant parasites in a nucleotide
      sequence-dependent manner. This technology represents an alternative method for
      identifying malarial genes as potential drug targets.

PMID- 8552673
TI  - Bacterial cell division protein FtsZ assembles into protofilament sheets and
      minirings, structural homologs of tubulin polymers.
AB  - The bacterial cell division protein FtsZ is a homolog of tubulin, but it has not
      been determined whether FtsZ polymers are structurally related to the microtubule
      lattice. In the present study, we have obtained high-resolution electron
      micrographs of two FtsZ polymers that show remarkable similarity to tubulin
      polymers. The first is a two-dimensional sheet of protofilaments with a lattice
      very similar to that of the microtubule wall. The second is a miniring,
      consisting of a single protofilament in a sharply curved, planar conformation.
      FtsZ minirings are very similar to tubulin rings that are formed upon disassembly
      of microtubules but are about half the diameter. This suggests that the curved
      conformation occurs at every FtsZ subunit, but in tubulin rings the conformation
      occurs at either beta- or alpha-tubulin subunits but not both. We conclude that
      the functional polymer of FtsZ in bacterial cell division is a long thin sheet of
      protofilaments. There is sufficient FtsZ in Escherichia coli to form a
      protofilament that encircles the cell 20 times. The similarity of polymers formed
      by FtsZ and tubulin implies that the protofilament sheet is an ancient
      cytoskeletal system, originally functioning in bacterial cell division and later
      modified to make microtubules.

PMID- 8552674
TI  - Hydrated myoglobin's anharmonic fluctuations are not primarily due to dihedral
      transitions.
AB  - To characterize the functionally important anharmonic motions of proteins,
      simulations of carboxymyoglobin (MbCO) dynamics have been performed during which
      dihedral transitions were prohibited. Comparison of torsionally restrained and
      unrestrained protein dynamics simulated at three levels of hydration and at
      temperatures ranging from 100 to 400 K suggests that hydration "catalyzes"
      protein mobility by facilitating collective anharmonic motions that do not
      require dihedral transitions. When dihedral transitions were prohibited,
      dehydrated MbCO, to a good approximation, exhibited only harmonic fluctuations,
      whereas hydrated MbCO exhibited both harmonic and anharmonic motions. The
      fluctuation of helix centers of mass also remained highly anharmonic in the
      torsionally restrained hydrated system. Atomic mean-square fluctuation at 300 K
      was reduced upon prohibition of dihedral transitions by only 28% and 10% for MbCO
      hydrated by 350 and 3830 water molecules, respectively.

PMID- 8552675
TI  - A mean field model of ligand-protein interactions: implications for the
      structural assessment of human immunodeficiency virus type 1 protease complexes
      and receptor-specific binding.
AB  - We propose a general mean field model of ligand-protein interactions to determine
      the thermodynamic equilibrium of a system at finite temperature. The method is
      employed in structural assessments of two human immuno-deficiency virus type 1
      protease complexes where the gross effects of protein flexibility are
      incorporated by utilizing a data base of crystal structures. Analysis of the
      energy spectra for these complexes has revealed that structural and thermo
      dynamic aspects of molecular recognition can be rationalized on the basis of the
      extent of frustration in the binding energy landscape. In particular, the
      relationship between receptor-specific binding of these ligands to human
      immunodeficiency virus type 1 protease and a minimal frustration principle is
      analyzed.

PMID- 8552676
TI  - High-level production of recombinant human lysosomal acid alpha-glucosidase in
      Chinese hamster ovary cells which targets to heart muscle and corrects glycogen
      accumulation in fibroblasts from patients with Pompe disease.
AB  - Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency
      of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme. We constructed
      a plasmid containing a 5'-shortened human acid alpha-glucosidase cDNA driven by
      the cytomegalovirus promoter, as well as the aminoglycoside phosphotransferase
      and dihydrofolate reductase genes. Following transfection in dihydrofolate
      reductase-deficient Chinese hamster ovary cells, selection with Geneticin, and
      amplification with methotrexate, a cell line producing high levels of the alpha
      glucosidase was established. In 48 hr, the cells cultured in Iscove's medium with
      5 mM butyrate secreted 110-kDa precursor enzyme that accumulated to 91
      micrograms.ml-1 in the medium (activity, > 22.6 mumol.hr-1.ml-1). This enzyme has
      a pH optimum similar to that of the mature form, but a lower Vmax and Km for 4
      methylumbelliferyl-alpha-D-glucoside. It is efficiently taken up by fibroblasts
      from Pompe patients, restoring normal levels of acid alpha-glucosidase and
      glycogen. The uptake is blocked by mannose 6-phosphate. Following intravenous
      injection, high enzyme levels are seen in heart and liver. An efficient
      production system now exists for recombinant human acid alpha-glucosidase
      targeted to heart and capable of correcting fibroblasts from patients with Pompe
      disease.

PMID- 8552677
TI  - Interactions of protein antigens with antibodies.
AB  - There are now several crystal structures of antibody Fab fragments complexed to
      their protein antigens. These include Fab complexes with lysozyme, two Fab
      complexes with influenza virus neuraminidase, and three Fab complexes with their
      anti-idiotype Fabs. The pattern of binding that emerges is similar to that found
      with other protein-protein interactions, with good shape complementarity between
      the interacting surfaces and reasonable juxtapositions of polar residues so as to
      permit hydrogen-bond formation. Water molecules have been observed in cavities
      within the interface and on the periphery, where they often form bridging
      hydrogen bonds between antibody and antigen. For the most part the antigen is
      bound in the middle of the antibody combining site with most of the six
      complementarity-determining residues involved in binding. For the most studied
      antigen, lysozyme, the epitopes for four antibodies occupy approximately 45% of
      the accessible surface area. Some conformational changes have been observed to
      accompany binding in both the antibody and the antigen, although most of the
      information on conformational change in the latter comes from studies of
      complexes with small antigens.

PMID- 8552678
TI  - Binding of the sigma 70 protein to the core subunits of Escherichia coli RNA
      polymerase, studied by iron-EDTA protein footprinting.
AB  - We have used a nonspecific protein cleaving reagent to map the interactions
      between subunits of the multisubunit enzyme RNA polymerase (Escherichia coli). We
      developed suitable conditions for using an untethered Fe-EDTA reagent, which does
      not bind significantly to proteins. Comparison of the cleaved fragments of the
      subunits from the core enzyme (alpha 2 beta beta') and the holoenzyme (core+sigma
      70) shows that absence of the sigma 70 subunit is associated with the appearance
      of several cleavage sites on the subunits beta (within 10 residues of sequence
      positions 745, 764, 795, and 812) and beta' (within 10 residues of sequence
      positions 581, 613, and 728). A cleavage site near beta residue 604 is present in
      the holoenzyme but absent in the core, demonstrating that a conformational change
      occurs when sigma 70 binds. No differences are observed for the alpha subunit.

PMID- 8552679
TI  - Cold shock induces a major ribosomal-associated protein that unwinds double
      stranded RNA in Escherichia coli.
AB  - A 70-kDa protein was specifically induced in Escherichia coli when the culture
      temperature was shifted from 37 to 15 degrees C. The protein was identified to be
      the product of the deaD gene (reassigned csdA) encoding a DEAD-box protein.
      Furthermore, after the shift from 37 to 15 degrees C, CsdA was exclusively
      localized in the ribosomal fraction and became a major ribosomal-associated
      protein in cells grown at 15 degrees C. The csdA deletion significantly impaired
      cell growth and the synthesis of a number of proteins, specifically the
      derepression of heat-shock proteins, at low temperature. Purified CsdA was found
      to unwind double-stranded RNA in the absence of ATP. Therefore, the requirement
      for CsdA in derepression of heat-shock protein synthesis is a cold shock-induced
      function possibly mediated by destabilization of secondary structures previously
      identified in the rpoH mRNA.

PMID- 8552680
TI  - Transcription elongation factor of respiratory syncytial virus, a nonsegmented
      negative-strand RNA virus.
AB  - RNA synthesis by the paramyxovirus respiratory syncytial virus, a ubiquitous
      human pathogen, was found to be more complex than previously appreciated for the
      nonsegmented negative-strand RNA viruses. Intracellular RNA replication of a
      plasmid-encoded "minigenome" analog of viral genomic RNA was directed by
      coexpression of the N, P, and L proteins. But, under these conditions, the
      greater part of mRNA synthesis terminated prematurely. This difference in
      processivity between the replicase and the transcriptase was unanticipated
      because the two enzymes ostensively shared the same protein subunits and
      template. Coexpression of the M2 gene at a low level of input plasmid resulted in
      the efficient production of full-length mRNA and, in the case of a dicistronic
      minigenome, sequential transcription. At a higher level, coexpression of the M2
      gene inhibited transcription and RNA replication. The M2 mRNA contains two
      overlapping translational open reading frames (ORFs), which were segregated for
      further analysis. Expression of the upstream ORF1, which encoded the previously
      described 22-kDa M2 protein, was associated with transcription elongation. A
      model involving this protein in the balance between transcription and replication
      is proposed. ORF2, which lacks an assigned protein, was associated with
      inhibition of RNA synthesis. We propose that this activity renders nucleocapsids
      synthetically quiescent prior to incorporation into virions.

PMID- 8552681
TI  - DNA-protein binding assays from a single sea urchin egg: a high-sensitivity
      capillary electrophoresis method.
AB  - A capillary electrophoresis method has been developed to study DNA-protein
      complexes by mobility-shift assay. This method is at least 100 times more
      sensitive than conventional gel mobility-shift procedures. Key features of the
      technique include the use of a neutral coated capillary, a small amount of linear
      polymer in the separation medium, and use of covalently dye-labeled DNA probes
      that can be detected with a commercially available laser-induced fluorescence
      monitor. The capillary method provides quantitative data in runs requiring < 20
      min, from which dissociation constants are readily determined. As a test case we
      studied interactions of a developmentally important sea urchin embryo
      transcription factor, SpP3A2. As little as 2-10 x 10(6) molecules of specific
      SpP3A2-oligonucleotide complex were reproducibly detected, using recombinant
      SpP3A2, crude nuclear extract, egg lysates, and even a single sea urchin egg
      lysed within the capillary column.

PMID- 8552682
TI  - Yeast actin: polymerization kinetic studies of wild type and a poorly
      polymerizing mutant.
AB  - Wild-type actin and a mutant actin were isolated from yeast (Saccharomyces
      cerevisiae) and the polymerization properties were examined at pH 8.0 and 20
      degrees C. The polymerization reaction was followed either by an increase in
      pyrene-labeled actin fluorescence or by a decrease in intrinsic fluorescence in
      the absence of pyrene-labeled actin. While similar to the properties of skeletal
      muscle actin, there are several important differences between the wild-type yeast
      and muscle actins. First, yeast actin polymerizes more rapidly than muscle actin
      under the same experimental conditions. The difference in rates may result from a
      difference in the steps involving formation of the nucleating species. Second, as
      measured with pyrene-labeled yeast actin, but not with intrinsic fluorescence,
      there is an overshoot in the fluorescence that has not been observed with
      skeletal muscle actin under the same conditions. Third, in order to simulate the
      polymerization process of wild-type yeast actin it is necessary to assume some
      fragmentation of the filaments. Finally, gelsolin inhibits polymerization of
      yeast actin but is known to accelerate the polymerization of muscle actin. A
      mutant actin (R177A/D179A) has also been isolated and studied. The mutations are
      at a region of contact between monomers across the long axis of the actin
      filament. This mutant polymerizes more slowly than wild type and filaments do not
      appear to fragment during polymerization. Elongation rates of the wild type and
      the mutant differ by only about 3-fold, and the slower polymerization of the
      mutant appears to result primarily from poorer nucleation.

PMID- 8552684
TI  - Forcing the market.

PMID- 8552685
TI  - The asthma specialist and patient education.
AB  - Despite the availability of effective treatments, morbidity and mortality in
      asthma are increasing. Patient education is essential if adverse factors in the
      control of asthma are to be overcome. Standard information and education given to
      patients in a respiratory clinic is insufficient. A formal asthma education
      programme delivered by an asthma nurse specialist improves patients'
      understanding of asthma and their inhaler technique.

PMID- 8552683
TI  - Association with capsid proteins promotes nuclear targeting of simian virus 40
      DNA.
AB  - All animal DNA viruses except pox virus utilize the cell nucleus as the site for
      virus reproduction. Yet, a critical viral infection process, nuclear targeting of
      the viral genome, is poorly understood. The role of capsid proteins in nuclear
      targeting of simian virus 40 (SV40) DNA, which is assessed by the nuclear
      accumulation of large tumor (T) antigen, the initial sign of the infectious
      process, was tested by two independent approaches: antibody interception
      experiments and reconstitution experiments. When antibody against viral capsid
      protein Vp1 or Vp3 was introduced into the cytoplasm, the nuclear accumulation of
      T antigen was not observed in cells either infected or cytoplasmically injected
      with virion. Nuclearly introduced anti-Vp3 IgG also showed the inhibitory effect.
      In the reconstitution experiments, SV40 DNA was allowed to interact with protein
      components of the virus, either empty particles or histones, and the resulting
      complexes were tested for the capability of protein components to target the DNA
      to the nucleus from cytoplasm as effectively as the targeting of DNA in the
      mature virion. In cells injected with empty particle-DNA, but not in
      minichromosome-injected cells, T antigen was observed as effectively as in SV40
      injected cells. These results demonstrate that SV40 capsid proteins can
      facilitate transport of SV40 DNA into the nucleus and indicate that Vp3, one of
      the capsid proteins, accompanies SV40 DNA as it enters the nucleus during virus
      infection.

PMID- 8552686
TI  - The changing pattern of employment in nursing.
AB  - A competitive and changing society places pressure on employers. Increasing
      flexibility, as well as added value, is expected from employees. Nurses need a
      strategy to survive, plus a wide range of skills.

PMID- 8552687
TI  - Teaching older patients about their medication.
AB  - Many elderly people have difficulty in taking their drugs correctly after
      discharge home from hospital. Individualised teaching can improve their
      compliance and quality of life.

PMID- 8552689
TI  - Skin cancer.

PMID- 8552688
TI  - The reliability of pressure sore risk-assessment tools.
AB  - Regular use of a risk-assessment tool may help increase and maintain staff
      awareness of pressure sore risk. All staff need to be educated in the use of the
      selected tool, to ensure reliability between users. A tool's threshold score
      should not be presumed appropriate in all patient areas. Care should be taken
      when using these scores to allocate preventive resources.

PMID- 8552690
TI  - Using a profile to develop a career plan.
AB  - A PREP profile records information that can help you to plan for the future.
      These sections of the profile will contain personal plans which do not have to be
      shown to others. The Rational Model of career planning provides a simple four
      stage structure to analyse career choices.

PMID- 8552691
TI  - Acne vulgaris.

PMID- 8552692
TI  - Management of breast disease in Asian women.
AB  - Breast cancer is the most common cause of death in women aged 35-55 years. Both
      Asian and European women would prefer a female physician to carry out
      examinations. Knowledge of breast cancer remains low among women from ethnic
      minorities. Communication and counselling services for Asian women need to be
      improved.

PMID- 8552693
TI  - Protein and energy food supplements.
AB  - Nurses must ensure that they are knowledgeable about nutrition--or the
      responsibility will be passed to untrained staff. There is a wide choice of food
      supplements, enabling cost-effective choices to be made.

PMID- 8552694
TI  - Using humour as an educational technique.
AB  - Humour can be constructive or destructive, so needs to be used selectively and
      sensitively. Teachers require training to acquire the appropriate level of self
      awareness, knowledge and skills. Educational humour needs monitoring and
      evaluation.

PMID- 8552695
TI  - Data collection using a palm-top computer.
AB  - Palm-top computers can be ideal for collecting nursing research data in the ward
      or community. The hand-held computer has several programs and special features
      that could be useful to the nurse researcher. The palm-top's limitations, as well
      as its advantages, must be considered in the light of the particular research
      project planned.

PMID- 8552696
TI  - Quality specifications and standard-setting for stoma care patients.
AB  - Quality specifications can be used as an information resource by purchasers of
      health care. The nature of service provision and nursing care can be positively
      influenced by the formalisation of standards and quality specifications. Auditing
      is essential in the ongoing evaluation of a quality system.

PMID- 8552697
TI  - The role of the nurse as the patient's advocate.
AB  - Advocacy is part of the nurse's role. Advocacy does not necessarily require
      confrontation. Nurses should not confuse acting in what they believe to be the
      patient's best interests with acting as a true patient advocate.

PMID- 8552698
TI  - A non-pharmacological approach to pain relief.
AB  - Effective pain management programmes must acknowledge the subjective nature of
      pain. Non-pharmacological pain management can be as effective, on occasions, as
      pharmacological pain management. Stress and anxiety evoke a similar physiological
      response to acute pain, highlighting the need for efficient cognitive management
      programmes.

PMID- 8552699
TI  - Surgical intervention for the repair of exomphalos.
AB  - Exomphalos carries a 67% chance of other serious defects, 37% of which are life
      threatening. Diagnosis in utero means parents can be counselled and offered
      choices of treatment. Parents need long-term support if their baby has a syndrome
      or other abnormalities. Babies that survive do well and most lead normal lives.

PMID- 8552700
TI  - Using massage in the relief of lymphoedema.
AB  - Lymphoedema of the arm is a complication of treatment for breast cancer. The
      condition often causes discomfort, reduced movement and changes in body image.
      Massage is one of the cornerstones of treatment. Aromatherapy massage is
      relaxing, increases patient comfort and promotes a therapeutic relationship
      between nurse and patient.

PMID- 8552701
TI  - Thrombolytic therapy.

PMID- 8552702
TI  - Reflective intuition: defining A&E nursing.
AB  - A&E nurses may develop intuitive feelings about the condition of their patients.
      A&E nurses are practising reflective intuition, based on experience. Recognition
      of this skill could raise the professional status of nursing.

PMID- 8552703
TI  - Insulin pens for the management of diabetes.
AB  - People with diabetes are faced with many choices as treatment and techniques
      improve. The nurse's role centres on education and empowerment. Insulin pens can
      provide increased independence and control for many people with diabetes.

PMID- 8552704
TI  - Infection control and urine drainage bag design.
AB  - Catheterisation carries a significant risk of infection. Catheter and drainage
      system design should reduce this risk. No one system will suit all users; new
      designs need extensive trials in use.

PMID- 8552705
TI  - The named nurse in the coronary care setting.
AB  - The named nurse concept was implemented almost overnight. Primary nursing ensures
      that each patient has a nurse who retains overall responsibility for that
      patient's nursing care.

PMID- 8552706
TI  - Using profiles in job and appraisal interviews.
AB  - Profiles provide the information needed to negotiate support for further training
      and development at appraisal. They should form the basis of a CV or job
      application. Selected sections from a profile may be presented at an appraisal or
      job interview.

PMID- 8552707
TI  - Protocols for the care of external fixator pin sites.
AB  - Pin site care methods used in the UK are based on doctor/nurse preference rather
      than research. There is a diversity of opinion regarding the best method of pin
      site care, and no standardised classification of pin site problems. There is a
      need for further research, either a multi-centre trial or in units with a high
      volume of work.

PMID- 8552708
TI  - The rising popularity of complementary therapies.
AB  - The range of complementary therapies available has increased. The treatments
      offered may improve the 'whole' person but not the 'part' which is diseased.
      Inquiry into the length and type of training of therapists is needed to ensure
      ethical practice. Recognition of the usefulness of some complementary therapies
      by orthodox medical practitioners is slowly increasing. Caution should continue
      to be exercised.

PMID- 8552709
TI  - Expression of functional oat phytochrome A in transgenic rice.
AB  - To investigate the biological functions of phytochromes in monocots, we
      generated, by electric discharge particle bombardment, transgenic rice (Oryza
      sativa cv Gulfmont) that constitutively expresses the oat phytochrome A
      apoprotein. The introduced 124-kD polypeptide bound chromophore and assembled
      into a red- and far-red-light-photoreversible chromoprotein with absorbance
      spectra indistinguishable from those of phytochrome purified from etiolated oats.
      Transgenic lines expressed up to 3 and 4 times more spectrophotometrically
      detectable phytochrome than wild-type plants in etiolated and green seedlings,
      respectively. Upon photo-conversion to the far-red-absorbing form of phytochrome,
      oat phytochrome A was degraded in etiolated seedlings with kinetics similar to
      those of endogenous rice phytochromes (half-life approximately 20 min). Although
      plants overexpressing phytochrome A were phenotypically indistinguishable from
      wild-type plants when grown under high-fluence white light, they were more
      sensitive as etiolated seedlings to light pulses that established very low
      phytochrome equilibria. This indicates that the introduced oat phytochrome A was
      biologically active. Thus, rice ectopically expressing PHY genes may offer a
      useful model to help understand the physiological functions of the various
      phytochrome isoforms in monocotyledonous plants.

PMID- 8552710
TI  - Overexpression of glutathione reductase but not glutathione synthetase leads to
      increases in antioxidant capacity and resistance to photoinhibition in poplar
      trees.
AB  - A poplar hybrid, Populus tremula x Populus alba, was transformed with the
      bacterial genes for either glutathione reductase (GR) (gor) or glutathione
      synthetase (GS) (gshII). When the gor gene was targeted to the chloroplasts, leaf
      GR activities were up to 1000 times greater than in all other lines. In contrast,
      targeting to the cytosol resulted in 2 to 10 times the GR activity. GR mRNA,
      protein, and activity levels suggest that bacterial GR is more stable in the
      chloroplast. When the gshII gene was expressed in the cytosol, GS activities were
      up to 100 times greater than in other lines. Overexpression of GR or GS in the
      cytosol had no effect on glutathione levels, but chloroplastic-GR expression
      caused a doubling of leaf glutathione and an increase in reduction state. The
      high-chloroplastic-GR expressors showed increased resistance to photoinhibition.
      The herbicide methyl viologen inhibited CO2 assimilation in all lines, but the
      increased leaf levels of glutathione and ascorbate in the high-chloroplastic-GR
      expressors persisted despite this treatment. These results suggest that
      overexpression of GR in the chloroplast increases the antioxidant capacity of the
      leaves and that this improves the capacity to withstand oxidative stress.

PMID- 8552712
TI  - The electronic Plant Gene Register.

PMID- 8552711
TI  - Multiple genes, tissue specificity, and expression-dependent modulationcontribute
      to the functional diversity of potassium channels in Arabidopsis thaliana.
AB  - K+ channels play diverse roles in mediating K+ transport and in modulating the
      membrane potential in higher plant cells during growth and development. Some of
      the diversity in K+ channel functions may arise from the regulated expression of
      multiple genes encoding different K+ channel polypeptides. Here we report the
      isolation of a novel Arabidopsis thaliana cDNA (AKT2) that is highly homologous
      to the two previously identified K+ channel genes, KAT1 and AKT1. This cDNA
      mapped to the center of chromosome 4 by restriction fragment length polymorphism
      analysis and was highly expressed in leaves, whereas AKT1 was mainly expressed in
      roots. In addition, we show that diversity in K+ channel function may be
      attributable to differences in expression levels. Increasing KAT1 expression in
      Xenopus oocytes by polyadenylation of the KAT1 mRNA increased the current
      amplitude and led to higher levels of KAT1 protein, as assayed in western blots.
      The increase in KAT1 expression in oocytes produced shifts in the threshold
      potential for activation to more positive membrane potentials and decreased half
      activation times. These results suggest that different levels of expression and
      tissue-specific expression of different K+ channel isoforms can contribute to the
      functional diversity of plant K+ channels. The identification of a highly
      expressed, leaf-specific K+ channel homolog in plants should allow further
      molecular characterization of K+ channel functions for physiological K+ transport
      processes in leaves.

PMID- 8552713
TI  - Identification and characterization of a phloem-specific beta-amylase.
AB  - A monoclonal antibody, RS 5, was raised by injecting sieve elements isolated from
      tissue cultures of Streptanthus tortuosus (Brassicacae) into BALB/c mice and
      screening resultant hybridoma supernatants for the labeling of phloem using
      immunofluorescence microscopy. The RS 5 monoclonal antibody identifies a 57-kD
      protein on immunoblots, which is present in phloem-forming tissue cultures of S.
      tortuosus but is absent in cultures that lack phloem. Purified 57-kD protein of
      S. tortuosus is demonstrated to be a phloem-specific beta-amylase. Partial
      peptide sequences of the 57-kD protein of S. tortuosus are shown to be 96%
      identical with the corresponding portions of a deduced sequence reported for a
      major form of beta-amylase in Arabidopsis thaliana. The RS 5 antibody cross
      reacts with the major form of A. thaliana beta-amylase on immunoblots, and the
      antibody also binds to the sieve elements of A. thaliana using immunofluorescence
      microscopy. The results suggest that the major form of A. thaliana beta-amylase
      is a phloem-specific enzyme.

PMID- 8552714
TI  - Formation of the ferritin iron mineral occurs in plastids.
AB  - Ferritin in plants is a nuclear-encoded, multisubunit protein found in plastids;
      an N-terminal transit peptide targets the protein to the plastid, but the site
      for formation of the ferritin Fe mineral is unknown. In biology, ferritin is
      required to concentrate Fe to levels needed by cells (approximately 10(-7) M),
      far above the solubility of the free ion (10(-18) M); the protein directs the
      reversible phase transition of the hydrated metal ion in solution to hydrated Fe
      oxo mineral. Low phosphate characterizes the solid-phase Fe mineral in the center
      of ferritin of the cytosolic animal ferritin, but high phosphate is the hallmark
      of Fe mineral in prokaryotic ferritin and plant (pea [Pisum sativum L.] seed)
      ferritin. Earlier studies using x-ray absorption spectroscopy showed that high
      concentrations of phosphate present during ferritin mineralization in vivo
      altered the local structure of Fe in the ferritin mineral so that it mimicked the
      prokaryotic type, whether the protein was from animals or bacteria. The use of x
      ray absorption spectroscopy to analyze the Fe environment in pea-seed ferritin
      now shows that the natural ferritin mineral in plants has an Fe-P interaction at
      3.26A, similar to that of bacterial ferritin; phosphate also prevented formation
      of the longer Fe-Fe interactions at 3.5A found in animal ferritins or in pea-seed
      ferritin reconstituted without phosphate. Such results indicate that ferritin
      mineralization occurs in the plastid, where the phosphate content is higher; a
      corollary is the existence of a plastid Fe uptake system to allow the
      concentration of Fe in the ferritin mineral.

PMID- 8552715
TI  - An Arabidopsis thaliana thionin gene is inducible via a signal transduction
      pathway different from that for pathogenesis-related proteins.
AB  - Two cDNAs encoding thionin preproteins have been isolated from Arabidopsis
      thaliana. The corresponding genes have been designated Thi2.1 and Thi2.2.
      Southern blot analysis suggests that A. thaliana most probably contains single
      genes for both thionins. Thi2.2 transcripts have a low basal level in seedlings
      and show circadian variation. Thi2.2 transcripts were also detected in rosette
      leaves. No potent elicitors have been found for the Thi2.2 gene. Transcripts of
      the Thi2.1 gene are not detectable in seedlings but are present in rosette leaves
      and at a very high level in flowers and in siliques. The expression of the Thi2.1
      gene is highly inducible in seedlings by pathogens, silver nitrate, and methyl
      jasmonate, but not by salicylate, indicating that the gene is induced by a signal
      transduction pathway that is at least partly different from that for the
      pathogenesis-related proteins.

PMID- 8552716
TI  - A structural model for the mechanisms of elicitor release from fungal cell walls
      by plant beta-1,3-endoglucanase.
AB  - The release of elicitor-active carbohydrates from fungal cell walls by beta-1,3
      endoglucanase contained in host tissues has been implicated as one of the
      earliest processes in the interaction between soybean (Glycine max) and the
      fungal pathogen Phytophthora megasperma f. sp. glycinea leading to host defense
      responses such as phytoalexin production. The present study was conducted to
      evaluate the primary structure of the glucanase-released elicitor (RE). Gel
      filtration chromatography of carbohydrates released from mycelial walls by
      purified soybean beta-1,3-endoglucanase resolved them into the four fractions
      (elicitor-active RE-I, -II, and -III and elicitor-inactive RE-IV). Sugar
      composition analysis indicated that all of the fractions were composed almost
      entirely of glucose. 1H- and 13C-nuclear magnetic resonance analysis indicated
      the presence of both beta-1,3- and beta-1,6-linkages for the elicitor-active RE
      I, -II, and -III fractions and only beta-1,3 linkage for the elicitor-inactive RE
      IV fraction. Methylation analysis and degradation studies employing beta-1,3-endo
      and beta-1,3-exoglucanase further suggested that the basic structure of elicitor
      active RE consists of beta-1,6-linked glucan backbone chains of various lengths
      with frequent side branches composed of beta-1,3-linked one or two glucose
      moieties. From these structural analyses of RE, a structural model of how RE is
      originally present in fungal cell walls and released by host beta-1,3
      endoglucanase is also proposed.

PMID- 8552717
TI  - Molecular cloning and characterization of a soluble inorganic pyrophosphatase in
      potato.
AB  - A cDNA clone encoding a soluble inorganic pyrophosphatase (EC 3.6.1.1) of potato
      (Solanum tuberosum L.) was isolated by screening a developing tuber library with
      a heterologous probe. The central domain of the encoded polypeptide is nearly
      identical at the sequence level with its Arabidopsis homolog (J.J. Kieber and
      E.R. Signer [1991] Plant Mol Biol 16: 345-348). Computer-assisted analysis of the
      potato, Arabidopsis, and Escherichia coli soluble pyrophosphatases indicated a
      remarkably conserved organization of the hydrophobic protein domains. The
      enzymatic function of the potato protein could be deduced from the presence of
      amino acid residues highly conserved in soluble pyrophosphatases and was
      confirmed by its capacity to complement a thermosensitive pyrophosphatase
      mutation in E. coli. The potato polypeptide was purified from complemented
      bacterial cells and its pyrophosphatase activity was shown to be strictly
      dependent on Mg2+ and strongly inhibited by Ca2+. The subcellular location of the
      potato pyrophosphatase is unknown. Structure analysis of the N-terminal protein
      domain failed to recognize typical transit peptides and the calculated molecular
      mass of the polypeptide (24 kD) is significantly inferior to the values reported
      for the plastidic (alkaline) or mitochondrial pyrophosphatases in plants (28-42
      kD). Two unlinked loci could be mapped by restriction fragment length
      polymorphism analysis in the potato genome using the full-length cDNA as probe.

PMID- 8552718
TI  - Copper-sensitive mutant of Arabidopsis thaliana.
AB  - A Cu-sensitive mutant, cup1-1, of Arabidopsis thaliana has a pattern of heavy
      metal sensitivity different from that of the cad1 and cad2 mutants, which are
      deficient in phytochelatin biosynthesis. The latter are significantly sensitive
      to Cd and Hg and only slightly sensitive to Cu, whereas the cup1-1 mutant is
      significantly sensitive to Cu, slightly sensitive to Cd, and not more sensitive
      to Hg, compared to the wild type. Genetic analysis has shown that the sensitive
      phenotype is recessive to the wild type and segregates as a single Mendelian
      locus, which has been mapped to chromosome 1. Genetic and biochemical studies
      demonstrate that the cup1-1 mutant is not affected in phytochelatin biosynthesis
      or function. The sensitive phenotype of the cup1-1 mutant is associated with, and
      probably due to, increased accumulation of higher levels of Cd and Cu compared
      with the wild type. Consistent with this, a Cu-inducible, root-specific
      metallothionein gene, MT2a, is expressed in cup1-1 roots under conditions in
      which it is not expressed in the wild type. Undifferentiated cup1-1 callus tissue
      did not show the Cu-sensitive phenotype, suggesting that the mutant phenotype, in
      contrast to cad1 and cad2, is not expressed at the cellular level.

PMID- 8552719
TI  - Antifreeze proteins in winter rye are similar to pathogenesis-related proteins.
AB  - The ability to control extracellular ice formation during freezing is critical to
      the survival of freezing-tolerant plants. Antifreeze proteins, which are proteins
      that have the ability to retard ice crystal growth, were recently identified as
      the most abundant apoplastic proteins in cold-acclimated winter rye (Secale
      cereale L.) leaves. In the experiments reported here, amino-terminal sequence
      comparisons, immuno-cross-reactions, and enzyme activity assays all indicated
      that these antifreeze proteins are similar to members of three classes of
      pathogenesis-related proteins, namely, endochitinases, endo-beta-1,3-glucanases,
      and thaumatin-like proteins. Apoplastic endochitinases and endo-beta-1,3
      glucanases that were induced by pathogens in freezing-sensitive tobacco did not
      exhibit antifreeze activity. Our findings suggest that subtle structural
      differences may have evolved in the pathogenesis-related proteins that accumulate
      at cold temperatures in winter rye to confer upon these proteins the ability to
      bind to ice.

PMID- 8552720
TI  - A new 1-aminocyclopropane-1-carboxylic acid-conjugating activity in tomato fruit.
AB  - A new conjugate, 1-(gamma-L-glutamylamino)cyclopropane-1-carboxylic acid (GACC),
      of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) is
      identified. The only previously identified conjugate of ACC is 1
      (malonylamino)cyclopropane-1-carboxylic acid (MACC). GACC, not MACC, was the
      major conjugate formed by crude protein extracts of tomato (Lycopersicon
      esculentum Mill cv Ailsa Craig) fruit pericarp and seeds incubated with [14C]ACC.
      GACC was resolved from [14C]ACC and [14C]MACC by reversed-phase C18 thin-layer
      chromatography and subsequently detected and quantified using a radioisotope
      imaging system. Proteins precipitated from crude extracts failed to catalyze
      formation of GACC unless the supernatant was added back. Reduced glutathione, but
      not other reducing agents, replaced the crude supernatant. When [35S
      cysteine]glutathione and [3H-2-glycine]glutathione were used as substrates,
      neither radiolabeled glycine nor cysteine from the glutathione tripeptide was
      incorporated into GACC. Oxidized glutathione, S-substituted glutathione, and di-
      and tripeptides having an N-terminal gamma-L-glutamic acid, but lacking cysteine
      and glycine, also served as substrates for GACC formation. Peptides lacking the N
      terminal gamma-L-glutamic acid did not serve as substrates. Acid hydrolysis of
      GACC yielded ACC, suggesting that GACC is an amide-linked conjugate of ACC. Taken
      together, these results indicate that GACC is 1-(gamma-glutamylamino)cyclopropane
      1-carboxylic acid and that its formation is catalyzed by a gamma
      glutamyltranspeptidase. Gas chromatography-mass spectrometry analysis of the N
      acetyl dimethyl ester of GACC confirmed this structure.

PMID- 8552721
TI  - Comparison of metallothionein gene expression and nonprotein thiols in ten
      Arabidopsis ecotypes. Correlation with copper tolerance.
AB  - Seedlings of 10 Arabidopsis ecotypes were compared with respect to copper
      tolerance, expression of two metallothionein genes (MT1 and MT2), and nonprotein
      thiol levels. MT1 was uniformly expressed in all treatments, and MT2 was copper
      inducible in all 10 ecotypes. MT1 and MT2 mRNA levels were compared with various
      growth parameters for the 10 ecotypes in the presence of 40 microM Cu2+. The best
      correlation (R = 0.99) was obtained between MT2 mRNA and the rate of root
      extension. MT2 mRNA levels also paralleled the recovery phase following
      inhibition by copper. Induction of MT2 mRNA was initiated at copper
      concentrations below the threshold for growth inhibition. In cross-induction
      experiments, Ag+, Cd2+, Zn2+, Ni2+, and heat shock all induced significant levels
      of MT2 gene expression, whereas Al3+ and salicylic acid did not. The correlation
      between copper tolerance and nonprotein thiol levels in the 10 ecotypes was not
      statistically significant. However, 2 ecotypes, Ws and Enkheim, previously shown
      to exhibit an acclimation response, had the highest levels of nonprotein thiols.
      We conclude that MT2 gene expression may be the primary determinant of ecotypic
      differences in the copper tolerance of nonpretreated Arabidopsis seedlings.

PMID- 8552722
TI  - Evidence that spinach leaves express calreticulin but not calsequestrin.
AB  - The presence of either calreticulin (CR) or calsequestrin (CS-like proteins in
      spinach (Spinacia oleracea L.) leaves has been previously described. Here we
      report the purification from spinach leaves of two highly acidic (isoelectric
      point 5.2) Ca(2+)-binding proteins of 56 and 54 kD by means of DEAE-cellulose
      chromatography followed by phenyl-Sepharose chromatography in the presence of
      Zn(2+) (i.e., under experimental conditions that allowed the purification of CR
      from human liver). On the other hand, we failed to identify any protein sharing
      with animal CS the ability to bind to phenyl-Sepharose in the absence of Ca(2+).
      Based on the N-terminal amino acid sequence, the 56- and 54-kD spinach Ca(2+)
      binding proteins were identified as two distinct isoforms of CR. Therefore, we
      conclude that CR, and not CS, is expressed in spinach leaves. The 56-kD spinach
      CR isoform was found to be glycosylated, as judged by ligand blot techniques with
      concanavalin A and affinity chromatography with concanavalin A-Sepharose.
      Furthermore, the 56-kD CR was found to differ from rabbit liver CR in amino acid
      sequence, peptide mapping after partial digestion with Staphylococcus aureus V8
      protease, pH-dependent shift of electrophoretic mobility, and immunological cross
      reactivity with an antiserum raised to spinach CR, indicating a low degree of
      structural homology with animal CRs.

PMID- 8552724
TI  - [Toward independence of the mentally disabled and encouragement of their social
      participation--establishment of a basic law for their aid and user movements].

PMID- 8552723
TI  - Cloning of a coconut endosperm cDNA encoding a 1-acyl-sn-glycerol-3-phosphate
      acyltransferase that accepts medium-chain-length substrates.
AB  - Immature coconut (Cocos nucifera) endosperm contains a 1-acyl-sn-glycerol-3
      phosphate acyltransferase (LPAAT) activity that shows a preference for medium
      chain-length fatty acyl-coenzyme A substrates (H.M. Davies, D.J. Hawkins, J.S.
      Nelsen [1995] Phytochemistry 39:989-996). Beginning with solubilized membrane
      preparations, we have used chromatographic separations to identify a polypeptide
      with an apparent molecular mass of 29 kD, whose presence in various column
      fractions correlates with the acyltransferase activity detected in those same
      fractions. Amino acid sequence data obtained from several peptides generated from
      this protein were used to isolate a full-length clone from a coconut endosperm
      cDNA library. Clone pCGN5503 contains a 1325-bp cDNA insert with an open reading
      frame encoding a 308-amino acid protein with a calculated molecular mass of 34.8
      kD. Comparison of the deduced amino acid sequence of pCGN5503 to sequences in the
      data banks revealed significant homology to other putative LPAAT sequences.
      Expression of the coconut cDNA in Escherichia coli conferred upon those cells a
      novel LPAAT activity whose substrate activity profile matched that of the coconut
      enzyme.

PMID- 8552725
TI  - [Analytic study on EEG features of aging with/without psychiatric disorders:
      focussing at the alterations in the EEGs of the healthy, depressive and demented
      elderlies].
AB  - The EEG alterations attributed to senescence are the complex result of functional
      as well as organic factors, such as normal physiological aging, pathological
      process which results in cognitive deterioration, and/or psychological phenomena
      including depression. The aim of this study is to clarify which factors influence
      which EEG features and to evaluate the relationship between the clinical and
      electrophysiological indices. For simplicity, this study focused on the major
      three factors that are important in dealing with senescence; 1) normal,
      physiological aging; 2) dementia; 3) depression. A total of 191 subjects
      participated in this study. The subject groups were classified into 9 groups
      based on their age and pathology. Two healthy elderly groups (N = 60; between the
      ages of 60 and 80 years; subclassified according to their social activity), a
      healthy young volunteers' group (N = 30; between the ages of 20 and 39), a
      healthy middle-aged volunteers' group (N = 30; between the ages of 40 and 59),
      four subject groups of dementia of Alzheimer's type [DAT] classified according to
      the severity of dementia (total number of subjects = 44), depressive elderly
      subjects (N = 12), and one group of subjects who are older than 80 years (N =
      15). The depressive subjects were diagnosed as major depression with their main
      symptom being psychomotor retardation which resembles the clinical picture of
      early dementia. The EEGs change with age. This well-approved fact is also
      confirmed in this study based on ANOVA. Within the same age groups, there were
      little differences in EEGs regardless of the quality of their social activities.
      More slow activity, more 20-32Hz fast activity, and less 13.5-20.0Hz beta
      activity were seen in the socially-inactive group than in the socially-active
      group (multiple range test based on Tukey's method). The fact that no tendency of
      increases in slow and fast activities accompanied by a decrease of alpha activity
      were seen in the socially-active group suggest that having such tendency in their
      EEG features may be indicative of underlying pathological process that are
      qualitatively different from normal physiological aging. The moderate grade of
      those change may not yet cause clinical impairment noticeable as dementia, but
      appear as less social activity. The EEGs of depressed elderly differed from the
      socially-inactive elderly as well as the mild dementia particularly in beta
      frequency bands. There were no significant differences between the socially
      inactive elderly and the mild dementia. The tendency of an increase of slow
      activity and a decrease of alpha activity was seen as the clinical severity of
      dementia increases. However, these changes reached at the statistically
      significant level only in the extremely demented subject group. To extract the
      feature indices of the EEGs, PCA was applied. Five principal components were
      descriptive of 88% of the data. The EEG features summarized by these components
      could differentiate the socially-active elderly and the socially-inactive
      elderly, and the depressed group was distinctively differed from other groups.
      Interestingly PCA showed the similarity between the socially-inactive elderly and
      the mild dementia, and the similarity between the middle-aged and the young
      volunteers. Except for the extreme dementia, subgroups of DAT patients according
      to the clinical severity did not show distinctive differences in EEG features.
      The correlation among the EEG derivations was investigated using cluster
      analysis. The result indicated that the interhemispheric electrophysiological
      correlation diminishes along with the advancement of the pathological process of
      the brain. This study indicated that the EEG indices derived from the
      multivariate analyses are more informative in regard to the relationship among
      EEG variables as well as these spatial relationship than evaluating the changes
      in each frequency band alone.

PMID- 8552726
TI  - [A study on the difference between clinical and neuropathological diagnoses of
      age-related dementing illnesses; correlations with Hachinski's ischemic score].
AB  - In this study, clinical diagnosis and results of neuropathological examination
      were analyzed on 55 demented patients serially autopsied in a geriatric hospital.
      Based on clinical observations including Hachinski's ischemic score and CT scan,
      30 cases were diagnosed as vascular dementia (VD), 16 cases as Alzheimer-type
      dementia (ATD), 6 as mixed-type dementia (MD), and 5 as other types of dementias.
      On the results of neuropathological examination, 25 cases were diagnosed as ATD,
      19 cases as VD, 5 as diffuse Lewy body disease (DLBD), 4 as MD, and 2 as other
      types of dementias. The accuracy of the clinical diagnosis for ATD was 78.6%, and
      that for VD was 53.3%. Thus, misdiagnosis was more frequent on VD. Clinically, VD
      cases were rarely misdiagnosed as ATD, while ATD or MD cases were more frequently
      misdiagnosed as VD. Therefore, it is suggested that VD is overdiagnosed. One of
      the reasons is that risk factors of cerebrovascular disorders increase and
      Hachinski's ischemic score also becomes higher with the age of the patients. ATD
      is clinically diagnosed only after excluding other dementing illnesses. More
      detailed analysis of clinical features including cognitive function and brain
      images is required for more accurate clinical diagnosis of age-related dementing
      illnesses. Also in our series, DLBD was the second most frequent degenerative
      dementia following ATD, although all DLBD cases were clinically misdiagnosed as
      ATD or VD.

PMID- 8552727
TI  - [Two cases of depressive disorder after pacemaker implantation].
AB  - We report 2 patients who showed psychological symptoms after pacemaker
      implantation. Pacemaker syndrome was excluded, and a diagnosis of depressive
      disorder not otherwise specified was made in both patients. Patient 1 complained
      of discomfort early after pacemaker implantation but became unaware of the
      pacemaker after 1 year. However, after 3 years, lack of activity, general
      fatigue, and unaccountable sensations developed. These symptoms improved with
      symbiosis with the pacemaker. Patient 2 developed many complications after
      pacemaker implantation. Therefore, he was markedly aware of the pacemaker as not
      self and wanted to remove it. One month after implantation, unaccountable
      sensations and irritations began to occur. He did not return to work, and the
      symptoms improved with progression of "mourning for the loss of the perfection of
      the own body". In both patients, their symptoms improved after "acceptance that
      their own body depended on the pacemaker" and "symbiosis with the pacemaker as
      not-self", not complete integration of the pacemaker. Therefore, the
      psychological process after pacemaker implantation consisted of the establishment
      of "mourning for the loss of the perfection of the own body" and "symbiosis with
      not-self". In these patients, this process was impaired, causing depressive
      symptoms. This process resembled the integration process in patients undergoing
      dialysis or renal transplantation. As, compared with renal transplantation, it is
      more difficult to integrate the pacemaker to the own body, so, it seems better to
      aim for "symbiosis with the pacemaker" to promote the adjustment process. To
      promote the adjustment process and decrease depression, support after
      understanding of this psychological process is needed.

PMID- 8552728
TI  - [Expressed emotion and six-month treatment of outcome of depressive outpatients
      with mood disorder].
AB  - The relationship of the Expressed Emotion (EE) and the outcome of 45 major
      depressive outpatients with DSM-II-R Mood Disorder was investigated for 6 month
      prospectively. In the non-remission group (n = 19, 42.2%), past history of major
      depressive episode was significantly high (p < .01), and there were more high-EE
      relatives (p < .05) than in the remission group (n = 26). Including borderline-EE
      (b-EE) as high-EE, the patients in the non-remission group were also more likely
      to live with high-EE relatives (p < .01) than those in the remission group. On
      the EE profile rated by the Five Minute Speech Sample, high-EE was 13.3% (n = 6).
      In the high-EE relatives, 3 were rated as emotional over-involvement (EOI), 2
      were Critical, and 1 was EOI and Critical. All of b-EE, (15.6%; n = 7) were rated
      as the b-Critical. On the Critical subscale, the rate of non-remission increased
      gradually in the response of the level of criticism (from pure low-EE, b
      Critical, and to Critical). With the Hayashi's second method of quantification,
      the level of criticism and past history of depression correlated with six month
      outcome. These results might indicate the problem of vicious circle around the
      recurence, criticism of families, and relapse or prolongation of the episode in
      depression. It was also suggested that a careful psychoeducational family
      approach focusing to reduce the negative escalation for patients and their
      families would contribute to the treatment for mood disorder.

PMID- 8552729
TI  - [An autopsy case of corticobasal degeneration clinically misdiagnosed as Pick's
      disease].
AB  - We report a 69-year-old woman who was clinically diagnosed as having a frontal
      lobe-type of Pick's disease. The initial symptoms were personality changes and
      problematic behaviors. The patient showed intellectual decline, "stehende
      Redensarten" and abnormal attitude in interpersonal situations such as
      inattentiveness and indifference in the course of the disease. Brain CT revealed
      a marked atrophy of the frontal lobes. In the terminal stage the patient had
      severe dementia, mutism, parkinsonism and cervical dystonia. Neuropathologically,
      there was a marked atrophy of the frontal lobes. The superior frontal gyrus was
      most severely atrophic. Histological study revealed mild to moderate loss of
      neurons, hyperplasia of protoplasmic astrocytes and many balooned neurons in the
      deep layers of the atrophied cerebral cortex. Severe neuronal loss was even seen
      only in a part of the superior frontal gyrus. The cerebral white manner showed
      marked diffuse fibrillary gliosis. There was neuronal loss with gliosis in the
      thalamus, lentiform nucleus, subthalamic nucleus, substantia nigra and inferior
      olivary nucleus. Marked gliosis was seen in the midbrain and pontine tegmentum.
      Sections from several levels of the spinal cord also showed marked gliosis of the
      gray matter. Antibodies against human tau stained massive argyrophilic thread
      like structures and oligodendroglial microtubular masses in the affected lesions.
      Neurofibrillary tangles were localized in the hippocampus and parahippocampal
      region. Neither Pick's body nor senile plaque were observed. Corticobasal
      degeneration (CBD) is a neurodegenerative disease initially presenting with
      unilateral motor disturbances. Typical initial symptoms are rigidity, akinesia
      and apraxia of an affected arm. The clinical phenotype might depend upon the
      affected areas of the cerebral cortex. Our patient initially exhibited
      personality changes and was clinically diagnosed as having Pick's disease.
      Although our case had unusual distribution pattern of the cerebral atrophy, it
      was pathologically diagnosed as CBD. The review of the literature suggests the
      presence of clinical varieties in CBD.

PMID- 8552730
TI  - Psychobiologic reactivity to stress and childhood respiratory illnesses: results
      of two prospective studies.
AB  - Psychological stress is thought to undermine host resistance to infection through
      neuroendocrine-mediated changes in immune competence. Associations between stress
      and infection have been modest in magnitude, however, suggesting individual
      variability in stress response. We therefore studied environmental stressors,
      psychobiologic reactivity to stress, and respiratory illness incidence in two
      studies of 236 preschool children. In Study 1, 137 3- to 5-year-old children from
      four childcare centers underwent a laboratory-based assessment of cardiovascular
      reactivity (changes in heart rate and mean arterial pressure) during a series of
      developmentally challenging tasks. Environmental stress was evaluated with two
      measures of stressors in the childcare setting. The incidence of respiratory
      illnesses was ascertained over 6 months using weekly respiratory tract
      examinations by a nurse. In Study 2, 99 5-year-old children were assessed for
      immune reactivity (changes in CD4+, CD8+, and CD19+ cell numbers, lymphocyte
      mitogenesis, and antibody response to pneumococcal vaccine) during the normative
      stressor of entering school. Blood for immune measures was sampled 1 week before
      and after kindergarten entry. Environmental stress was indexed with parent
      reports of family stressors, and a 12-week respiratory illness incidence was
      measured with biweekly, parent-completed symptom checklists. The two studies
      produced remarkably similar findings. Although environmental stress was not
      independently associated with respiratory illnesses in either study, the
      incidence of illness was related to an interaction between child care stress and
      mean arterial pressure reactivity (beta = .35, p < .05) in Study 1 and to an
      interaction between stressful life events and CD19+ reactivity (beta = .51, p <
      .05) in Study 2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8552731
TI  - Stress, reactivity, and disease.
AB  - In summary, this work is an ambitious attempt to address some key issues in
      regard to the clinical importance of reactivity. The authors should be
      complimented for their efforts in addressing these issues, especially in small
      children. However, it is necessary to view their data in light of both the
      studies' strengths and weaknesses and to evaluate the implications of the work in
      light of existing theory and evidence. From this perspective, we think the work
      provokes interesting ways to think about reactivity. However, it leaves to
      subsequent research the task of systematically addressing the many issues that it
      raises.

PMID- 8552732
TI  - Depressive symptomatology and hypertension-associated morbidity and mortality in
      older adults.
AB  - This study determines, in a population of older adults with diagnosed
      hypertension, the concurrent association between depressive symptomatology and
      blood pressure control and the longitudinal association between depressive
      symptomatology and blood pressure control, stroke, and cardiovascular-related
      mortality. Data are from the East Boston, Massachusetts; New Haven, Connecticut;
      and Iowa sites of the Established Populations for Epidemiologic Studies of the
      Elderly, conducted between 1982 and 1988. Age-adjusted site-and gender-specific
      analyses were conducted, unadjusted and adjusted for baseline health status.
      There was no consistent association, cross-sectionally or longitudinally, between
      depressive symptoms and blood pressure control. Rates of stroke were 2.3 to 2.7
      times higher in most subgroups with high depressive symptomatology in contrast to
      their nondepressed counterparts. Rates of cardiovascular disease-related death
      were also elevated in most subgroups, achieving statistical significance in women
      from New Haven and Iowa. This study presents evidence that high depressive
      symptoms in older adults with diagnosed hypertension may place them at increased
      risk of stroke and possibly cardiovascular-related death relative to other
      elderly persons with diagnosed hypertension. Because the rate of stroke in this
      subpopulation was exceptionally high, further evaluation of the role of
      depressive symptoms in the progression of hypertensive disease seems warranted.

PMID- 8552733
TI  - The role of depression in hypertension-related mortality.

PMID- 8552734
TI  - Depressive symptoms associated with symptoms of the temporomandibular joint pain
      and dysfunction syndrome.
AB  - This paper discusses the findings in the 1012 55-year-old inhabitants of Oulu (a
      medium-sized Finnish town), 780 of whom (77%) were examined. The purpose was to
      determine the possible associations between depressive symptoms and subjective
      and clinical symptoms of the temporomandibular joint pain and dysfunction
      syndrome (PDS). The PDS symptoms were determined using Helkimo's Clinical
      Dysfunction Index. Depressive symptoms in 768 subjects were determined using
      Zung's self-rating depression scale. The prevalences of high rates of depressive
      symptoms, subjective symptoms of PDS, and clinical symptoms of PDS in the
      population were 12.2%, 12.0%, and 4.9%, respectively. Subjective symptoms of PDS
      were more common in depressed dentate men and women than in nondepressed dentate
      men and women. There was a significantly higher prevalence of subjective symptoms
      of PDS in depressed edentulous women than in nondepressed edentulous women. There
      were significantly more moderate or severe clinical symptoms of PDS in depressed
      dentate women than in nondepressed dentate women. A similar trend was seen in
      dentate men. An integrated approach is of crucial importance in the diagnosis and
      treatment of depression and the temporomandibular joint pain and dysfunction
      syndrome.

PMID- 8552735
TI  - Perimenstrual depression: its relationship to pain, bleeding, and previous
      history of depression.
AB  - Daily ratings of depression, pain, and menstrual blood loss, as well as past
      history of treated depression, were analyzed in 210 women attending a
      Premenstrual Syndrome Clinic. Severity and duration of perimenstrual depression
      was strongly associated with the severity of premenstrual and menstrual pain,
      raising the possibility of a causal relationship. It is not yet clear whether the
      occurrence of depression alters a woman's perception of pain, pain aggravates a
      tendency to perimenstrual depression, or some common factor aggravates both. A
      relationship between depression and subjective ratings of blood loss was also
      observed but was less marked than the relationship with pain. Both relationships
      had been reported in an earlier study using retrospective ratings. A relationship
      between past history of treated depression and severity and timing of current
      perimenstrual depression, observed previously, was not found in this study. This
      discrepancy was not due to differences between retrospective and prospective
      methods of assessment, but may have partly resulted from differences in the
      reporting of premenstrual pain in the two studies. Further studies of this
      association should control for the confounding effect of pain.

PMID- 8552736
TI  - Personality factors in women with premenstrual syndrome.
AB  - The recently developed Tridimensional Personality Questionnaire (TPQ) was used to
      examine personality correlates in women diagnosed with premenstrual syndrome
      (PMS). The hypotheses were that the TPQ scores, specifically harm avoidance (HA),
      would be higher in PMS subjects than in the general population but lower than in
      depressed populations because major mood disorder is an exclusion from the PMS
      diagnosis; harm avoidance would have the strongest association with PMS, but
      other TPQ factors might characterize nondysphoric subgroups in the PMS
      population. The sample included 157 women who sought medical treatment and met
      clearly defined criteria for PMS. Two comparison groups of age-matched women with
      major depression (MDD, N = 20) and premenstrual exacerbation of major depression
      (MDD + PMS, N = 24) were also evaluated. TPQ scores were significantly higher for
      PMS subjects on all three dimensions compared with external normative TPQ data.
      The TPQ dimensions of HA and novelty seeking (NS) were modestly correlated with
      the premenstrual symptom scores. The HA dimension correlated with premenstrual
      depression and physical aches; high NS scores correlated with premenstrual food
      cravings, headache, and mood swings. As hypothesized, the HA scores were
      significantly higher in the comparison groups diagnosed with major depression;
      the NS and reward dependence (RD) dimensions did not differ between the PMS and
      MDD groups. PMS was associated with only modest nonnormative personality
      correlates, as assessed by the TPQ. Elevations of the HA and NS dimensions were
      associated with a tendency for the PMS to present with specific symptom patterns:
      depressive symptoms for the HA factor and food cravings and mood swings for the
      NS factor. Further research employing other assessment methods is needed to
      confirm these findings.

PMID- 8552737
TI  - Effect of chronic stress associated with unemployment on salivary cortisol:
      overall cortisol levels, diurnal rhythm, and acute stress reactivity.
AB  - This study examined the effect of chronic stress associated with unemployment on
      the magnitude of salivary cortisol excretion, on the diurnal rhythm of cortisol,
      and on cortisol reactivity to acute naturalistic stressors using Experience
      Sampling Methodology (ESM). Employed (N = 60) and unemployed (N = 60) subjects
      were studied for 2 days. Subjects were beeped 6 times per day by a preprogrammed
      wristwatch to assess acute stressors; 25 minutes after each ESM-beep, subjects
      were beeped a second time for saliva samples. The groups did not differ in their
      overall cortisol excretion or in cortisol reactivity to acute daily stressors.
      Compared to employed subjects, unemployed subjects had a diurnal pattern of
      cortisol excretion with relatively higher morning and lower evening levels.
      Subjects' daily activities and their locations were associated with diurnal
      rhythm differences.

PMID- 8552738
TI  - Persistent high cortisol responses to repeated psychological stress in a
      subpopulation of healthy men.
AB  - The present study tested the hypothesis that some subjects may not readily show
      habituation of adrenocortical stress responses to repeated psychological stress.
      Twenty healthy male subjects were each exposed five times to the same, brief
      psychosocial stressor (public speaking and mental arithmetic in front of an
      audience) with one stress session per day. Salivary cortisol levels were assessed
      as an index of adrenocortical stress responses. For the total group, cortisol
      levels were significantly elevated on each of the 5 days. The mean response
      decreased from day 1 to day 2; however, no further attenuation could be observed
      on the remaining days. Cluster analysis revealed two groups of subjects who
      showed completely different response kinetics. In the first group (N = 13),
      termed "low responders," cortisol levels were elevated on day 1 only. Day 2 to 5
      cortisol levels were unaltered. In contrast, subjects in the second group ("high
      responders") displayed large increases to each of the five experimental
      treatments. This group had no significant response decrement from day 1 to day 2
      to 4 and only a marginal response difference between day 1 and day 5.
      Discriminant analysis revealed that a combination of five personality scales plus
      the scores on a symptoms checklist significantly discriminated between high and
      low responders. With this discriminant function, all 20 subjects were correctly
      classified to the two groups. These results are discussed with a focus on the
      possible impact of adrenocortical response types on health and disease.

PMID- 8552739
TI  - Sensory focus as therapeutic treatments for acute pain.
AB  - This study examined the hypothesis that instructing patients to focus on their
      sensations (sensory focus) during root canal therapy reduces painful response.
      Before dental treatment, patients were randomly assigned to one of four
      audiotaped conditions: sensory focus with and without procedural information,
      procedural information, or no-intervention. Patients were categorized as to how
      much control they desired and felt. The "high desire for control/low felt
      control" subgroup's sensory pain intensity scores in the sensory focus condition
      were significantly lower than the "high desire for control/low felt control"
      subgroup's sensory intensity scores in the no-intervention comparison condition.
      This was true immediately after treatment (F(1,303) = 13.37; p < or = .001) and 1
      week after treatment (F(1,303) = 14.30; p < or = .001). Immediately after
      treatment, the high desire for control/low felt control subgroup in the
      sensory/procedural condition was significantly lower on sensory pain intensity
      scores than the high desire/low felt subgroup in the no-intervention condition
      (F(1,303) = 3.75; p < or = .001). This difference was not observed on the 1-week
      recall of pain. Adding procedural information to the instructions to focus on
      sensation did not increase the pain-reducing effects. Results extend prior
      findings that sensory focus significantly reduces sensory pain intensity only
      among patients who are classified as having a high desire for control and low
      perceived control. These results are congruent with theoretical arguments that
      coping preferences moderate the reaction of patients to various therapeutic
      strategies.

PMID- 8552740
TI  - Decreased bone mineral density in medicated psychiatric patients.
AB  - Osteoporosis is a common problem in postmenopausal women. It has been linked to
      estrogen deficiency, other neuroendocrine processes such as hypercortisolemia and
      male hypogonadism, nutritional deficiencies, and other mechanisms. Some of these
      changes have been also reported in male and female patients with mental
      disorders, especially those receiving psychotropic medications. Therefore, bone
      mineral density was measured by dual-photon absorptiometry in the lumbar spine
      and in the femoral neck of 33 female and 35 male consenting psychiatric
      inpatients admitted consecutively. Patients were diagnosed as having major
      depressive disorder (N = 21), schizophrenia (N = 33), schizoaffective disorder (N
      = 7), mania (N = 2), and adjustment disorder (N = 5). Plasma levels of prolactin,
      estrogen, cortisol, and testosterone were also measured in a subgroup of these
      patients. It is reported that female patients, but especially male patients, had
      a highly significant decrease in bone mineral density when compared with age- and
      sex-matched normal data. It is suggested that psychiatric patients treated with
      antidepressants or neuroleptics might have decreased bone mineral density than is
      normal for their age and sex, and may be at an increased risk for fractures.
      These results may be related to low levels of gonadal hormones, especially in
      male subjects. Data should be confirmed with a larger number of patients with and
      without medications to distinguish between diagnosis-related and treatment
      related effects.

PMID- 8552741
TI  - Conditioning allergic skin responses in humans: a controlled trial.
AB  - Classical conditioning of immune responsiveness has been extensively investigated
      in animals, but few successful studies have been reported with humans. We report
      the results of a study in which an attempt was made to demonstrate conditioned
      alteration to an allergic skin test response in humans. For 8 of 10 trials,
      allergic skin tests were administered to one forearm of volunteer subjects, and
      saline was administered to the other forearm. For the other two trials, the test
      substances were covertly switched between arms, but no changes in response
      resulted from this maneuver that could be ascribed to conditioning.

PMID- 8552742
TI  - Family history of hypertension influences neurobehavioral function in
      hypertensive patients.
AB  - This study examined the influence of family history of hypertension on
      neurobehavioral performance. Sixty-two hypertensive men and women who reported a
      family history of hypertension (+FH) were compared with 28 hypertensive
      individuals without a family history (-FH) and 32 normotensive control subjects.
      A neurocognitive test battery that included tests of information processing,
      verbal memory, and figural memory was administered individually to each patient.
      Results showed that +FH, compared with -FH and normotensive control subjects, was
      associated with poorer performance on three tests of attention and short-term
      memory (Sternberg reaction time, Trails B, and Digit Span). There were no
      differences between the groups on tests of either verbal or figural memory. Other
      variables, including gender, ethnicity, age, years of education, blood pressure,
      state anxiety, depression, and Type A behavior did not account for these results.
      In addition, +FH hypertensive subjects reported greater levels of state anxiety
      and depression compared with -FH hypertensive subjects and normotensive control
      subjects. The findings suggest a genetic link to impaired cognitive abilities, as
      observed among hypertensive patients relative to their normotensive counterparts.

PMID- 8552743
TI  - Improved hypertension control after disclosure of decades-old trauma.
AB  - This report presents the case of a 49-year-old woman who had been treated
      unsuccessfully for 6 years for longstanding severe and refractory essential
      hypertension. Although she reported no extraordinary stress or distress, her
      disclosure of a 3-decade-old rape and the experiencing of previously repressed
      and unconfided emotions related to it were followed by a dramatic and sustained
      improvement in her blood pressure. This case suggests that repressed emotions,
      which patients cannot report, may contribute substantially to the development of
      essential hypertension, even when they are related to decades-old events. More
      attention to repressed emotions, and better means of studying them, are needed
      before the mystery of the links between psychological factors and essential
      hypertension is unraveled.

PMID- 8552744
TI  - Rise in the number of asthma fatalities are poor patient education, lack of
      compliance, and underlying psychological disturbances.

PMID- 8552745
TI  - Contradictions in British vaccine policy on hepatitis B.
AB  - A vaccine for hepatitis B became available in the UK from 1982, but it did not
      solve the public health dilemmas presented by the disease. In the decade that
      followed, epidemiologically important groups such as intravenous drug users and
      gay men were not targetted, while the groups of health workers at the centre of
      policy concern received little vaccine. This paper draws on models of diffusion,
      the pattern of the disease, and previous policies on screening, to explain the
      restricted vaccine policy which was a field for contention through the 1980s and
      into the 1990s.

PMID- 8552746
TI  - [Child vaccination and its representations in Iran today: from Teheran to
      Hassanabad].
AB  - The reception of child immunization in Iran today can be explained by the
      conjunction of several factors. Firstly, the Pasteur Institute of Teheran
      (established in 1921) initiated the vaccine transfer, while the successive public
      health policies developed and systematized it. Since the Islamic Revolution, the
      application of the Expanded Program of Immunization has allowed the Islamic
      Republic of Iran to reach the fourth world-wide rank for immunisation of child
      populations. The socio-cultural appropriation of the technique can also be
      explained by its integration into the popular preventive practices (such as magic
      and religious rituals) as well as a specific treatment of the
      collective/individual question. This paper describes some results of a
      qualitative anthropological research conducted in Teheran and the rural district
      of Hassanabad (near Isfahan) between 1991 and 1992.

PMID- 8552747
TI  - Strategies of research for a vaccine against AIDS.
AB  - Retroviruses replicate by inserting their proviral DNA into host cell
      chromosomes, usually in cells of the immune system. Nevertheless, an efficacious
      and safe subunit recombinant vaccine has been prepared against the feline
      leukemia retrovirus of cats. Because of high rates of morbidity and mortality,
      particularly in the developing world, the development of a vaccine against human
      immunodeficiency virus type I (HIV-I) has become very important. The very high
      rate of mutation or variation of lentiviruses, such as HIV-I, makes a vaccine
      against this virus particularly difficult. Active research must be encouraged to
      design a modified envelope vaccine molecule of gp120 subtype E or C for trials in
      appropriate developing country settings.

PMID- 8552748
TI  - [Clinical experimentation with HIV vaccines: scientific and ethical dilemmas].
AB  - Developing a vaccine against HIV is one of the greatest challenges the scientific
      community faces today. Several vaccine candidates have undergone preliminary
      safety and immunogenicity studies in humans. Research teams are ready to test
      these vaccines in the field, yet the scientific community is divided as to
      whether efficacy trial should begin. This paper addresses the complex scientific
      and ethical issues raised by clinical trials. Considering the pressure to act
      rapidly to solve the crisis, scientists need to hold to the fundamental
      principles that guide decisions in biomedical research: respect for persons,
      beneficence and justice. Because these studies need to enroll a large number of
      subjects, prospective vaccines will need to be tested in developing, as well as
      industrial countries. The international community needs to work to ensure that
      the populations that accept the risk of the research receive the full benefit of
      that research and, that the vaccine proven successful, be made accessible and
      affordable to people in less economically developed situation.

PMID- 8552749
TI  - [Education or constraint: measles vaccination in France during the belle epoque].
AB  - The dreadful nature of the epidemic of 1870 explains why smallpox, not cholera,
      played a central role in the French public health regulations. And yet, France
      went it alone on the matter. The rules required isolation for the contagious sick
      and mandatory notification of the disease almost everywhere, nevertheless France
      relied only on persuasion. True, the public health law of 1902 provided the State
      with new weapons. But would such a mandatory decree be sufficient to awake
      popular opinion? There was no resistance to the law, like in England or Germany.
      However, the new regulations took several decades to be enforced, if only because
      of the poor state of the sanitary administration. Smallpox vaccination was
      eventually implemented when the authorities discovered that proximity and easier
      accessibility to services and facilities are of primary importance for patients.

PMID- 8552750
TI  - [Historical development of vaccines. Introduction: Hazards and rationality in the
      vaccinal approach].
AB  - The aim of this paper is to introduce the one hundred years of vaccination that
      has passed since Louis Pasteur first coined this generic term. According to the
      late Jonas Salk, vaccinology is a science encompassing all aspects of vaccine
      from its conception in the laboratory to its production by companies and its
      application and distribution in the field. In this historical survey I explore
      how vaccination never consisted of a simple and uniform application of a rational
      model, but rather diverged along various pathways, several of which were
      discarded in retrospect as being hazardous, and I analyse the ongoing interplay
      between rational and inventive thinking.

PMID- 8552751
TI  - [Smallpox control in Indochina: variolation vs vaccination?].
AB  - To the technical and administrative difficulties encountered by the propagation
      of Jennerian vaccination among Indochinese populations since the beginning of
      French colonization, was opposed the will to impose a western prophylactic
      method. This led to some aberrations, such as attempts of compulsive mass
      vaccination with an ineffective and/or unsafe product. There was also an inherent
      contradiction between the French medical service's proclaimed wish to apply
      vaccination to the entire Indochinese population and its suspicious attitude
      concerning the know-how of local practitioners. But the important small-pox
      endemicity in Indochina also made this tropical area a great ground for
      experience because it led to advances in vaccine production methods, e.g., from
      buffaloes, and even in the 'science of immunization'.

PMID- 8552752
TI  - Between bacteriology and virology: the development of typhus vaccines between the
      First and Second World Wars.
AB  - This paper provides an overview of the development of typhus vaccines between the
      first and second world wars. It is shown that there was a shift in the
      classification of the causal Rickettsiae from being classed as bacteria to being
      conceptualised as a type of virus. This 'paradigm switch' stimulated interest in
      the possibility of producing an effective medicine.

PMID- 8552753
TI  - Poliovaccines: lessons learnt and forgotten.
AB  - At the beginning of the twentieth century, poliomyelitis presented a scientific
      and medical challenge of a complexity similar to that of AIDS now. Research on
      polio, mainly in the US, gradually became focussed to solving basic questions,
      but was held up by the lack of suitable laboratory techniques. The financing of
      the research and the wide range of basic topics funded were the model for later
      medical science. The problem of polio, at least in the wealthier temperate
      countries, has been solved by the use of vaccines. Many fundamental questions
      about the mechanism of the disease remained unsolved and this lack of knowledge
      has contributed to many unfortunate accidents. The history of polio has many
      lessons for AIDS researchers.

PMID- 8552754
TI  - Nurse's role in hospital compliance with EMTALA.

PMID- 8552755
TI  - Does the "continuous treatment" doctrine apply to hospitals? Case in point:
      Horton v. Carolina Medicorp, Inc. 460 S.E. 2d 567--NC (1995).

PMID- 8552756
TI  - Legal case briefs for nurses. IL: insults exchanged--pt. attempts to leave:
      restraint proper under "necessity" doctrine; LA: workers' comp claim for on-job
      injury: "pre-existing condition" defense by employer.

PMID- 8552757
TI  - Nurses fail to "go over doctor's head": death results. Case in point: Strubhart
      v. Perry Mem. Hosp. Trus 903 P. 2d 263--OK (a995).

PMID- 8552758
TI  - [Penicillium ulaiense Hsieh, Su & Tzean, a post-harvest pathogen of citrus fruits
      in northeastern Argentina].
AB  - Fungi were isolated from the surface of decaying citrus fruits and their
      pathogenicity was determined. A few rotten fruits presented coremia of
      Penicillium ulaiense Hsieh, Su & Tzean, a new postharvest pathogen in Latin
      America. Penicillium digitatum (89 strains). Penicillium italicum (28). P.
      ulaiense (12) and Geotrichum candidum (11) were isolated from 129 samples of
      citrus fruits.

PMID- 8552759
TI  - [Evaluation of selective culture media for the isolation of Salmonella from
      poultry].
AB  - Rambach agar, xylose-lysine-deoxycholate agar (XLD) with different concentrations
      of Tergitol 4 or 7 ethyl-2 methyl-4 undecanol hydrogen sulphate, sodium salt
      (XLDT4), Salmonella-Shigella agar (SS) and bismuth sulfite agar according to
      Wilson-Blair (BS) were evaluated using Salmonella spp. serovars and other
      bacterial species from the intestinal flora of poultry. Growth of the most common
      Salmonella serovars isolated from chickens in our country were evaluated using a
      viable counting technique on the different selective media and these results were
      compared with those obtained on Columbia base (ABC) agar plus 7% bovine blood
      (Table 1). Samples from Salmonella experimentally inoculated chickens were also
      examined. Results showed that Rambach, SS and XLD or XLDT4 were all satisfactory
      for isolation of Salmonella. Bismuth Sulfite agar was too inhibitory for bacteria
      important in veterinary practice. The characteristic colonies of Salmonella and
      other common fecal contaminant bacteria growing on SS, Rambach, XLDT4 and SB are
      shown in Table 2. Addition of tergitol or novobiocin to XLD agar did not
      completely inhibit the growth of all Proteus spp. strains examined. None of the
      Proteus spp. strains able to multiply on SS, XLD or XLDT4 agar grew on the
      commercial Rambach agar. Several different contaminant bacterial species produced
      Salmonella-like colonies on Rambach, SS, XLD and XLDT4 agars. Because these
      contaminant bacterial species are different it is advisable to improve the
      diagnosis by culturing samples on SS, XLD or XLDT4 agar and also simultaneously
      on Rambach agar.

PMID- 8552760
TI  - [Development of Iodophanus carneus under different types of light].
AB  - Development of Iodophanus carneus was conditioned by light. Hyphal growth was
      photoinhibited. Light wavelength increases carotene contents being blue and near
      ultraviolet light the most effective. For ascocarp induction or inhibition, the
      most effective wavelengths were blue. The possible role of flavins is discussed.

PMID- 8552761
TI  - [In vitro sensitivity tests for yeasts: evaluation of a micromethod].
AB  - A microdilution antifungal susceptibility test for yeasts was evaluated, based on
      the macro broth dilution method standardized by the National Committee for
      Clinical Laboratory Standards (NCCLS) Subcommittee on Antifungal Susceptibility
      Testing. Both methods were compared using six reference strains with different
      patterns of susceptibility to the following antifungal drugs: amphotericin B
      (AMB), flucytosine (5FC), fluconazole (FCZ), itraconazole (ITZ), ketoconazole
      (KTZ) and miconazole (MCZ). Minimal inhibitory concentration (MIC) results
      obtained by both methods differed only in 1 or 2 dilutions. Microdilution MIC's
      determined as visual endpoints and as quantitative measurement of 80% inhibition
      of relative growth showed a significant correlation (p < 0.001) for AMB, 5FC,
      FCZ, MCZ and ITZ, conversely no correlation (p = 1.00) for KTZ was observed as
      determined with 47 local isolates of Candida albicans.

PMID- 8552762
TI  - [Determination of the antiviral activity of a naturally occurring sulfated
      xylomannan under various experimental conditions].
AB  - The effects of different experimental conditions on the antiviral activity of the
      sulphated xylomannan F6, isolated from the red seaweed Nothogenia fastigiata,
      against the replication of herpes simplex virus type 1 and 2 (HSV-1 and HSV-2)
      were studied. The compound was equally effective against several strains of HSV-1
      (F, KOS, B-2006 and Field) and HSV-2 (G) in different cell lines (Vero, HEp-2 and
      BHK-21). Furthermore, the antiviral activity of F6 was independent of the method
      employed to determine the 50% inhibitory concentration (IC50) (virus yield or
      plaque reduction tests). The value of the IC50 against HSV-1 was not
      significantly affected by the initial virus concentration since a variation in
      the multiplicity of infection from 0.0001 to 0.1 UFP/cell only increased twofold
      the IC50 from 0.61 to 1.35 micrograms/ml, respectively. The potent inhibitory
      effect of F6 against high doses of HSV-1 represents a significant advantage for
      this sulphated polysaccharide with respect to other compounds only active against
      low viral inocula.

PMID- 8552763
TI  - [Growth and survival of Azospirillum in roots and maize rhizospheres with
      different levels of acidity].
AB  - An experiment was carried out in order to evaluate the effect of pH on
      Azospirillum sp. growth and survival in maize rhizosphere. Sterilized maize seeds
      were sown in a perlite substratum with addition of a nutritive medium. The pots
      were buffered at two different pHs: 5.8 (group one) and 7.0 (group two). Each
      group was divided in two treatments: inoculated with Azospirillum sp. Az-39 and
      non-inoculated. Experimental pots were incubated at 20 degrees C with a 14 hour
      photoperiod. Growth of non-inoculated roots was negligible. Inoculated roots
      showed a better response at pH 5.8 than at 7.0. Several accompanying bacteria
      were found. Azospirillum grew in both groups with a low penetration into roots. A
      set of nutritive relationships among microorganisms and maize roots was observed;
      Xanthomonas is a maize pathogenic bacteria, and it is a NO3- consumer, and uses
      this anion as hydrogen acceptor. The Gram (-) Diplococcus is a nitrate producer .
      Cytophaga and Flavobacterium are related with roots decomposition. It is
      concluded that Azospirillum improves the root growth, mainly at pH 5.8.

PMID- 8552764
TI  - Neuropeptide converting and processing enzymes in the spinal cord and
      cerebrospinal fluid.

PMID- 8552765
TI  - Inactivation of neuropeptides.

PMID- 8552766
TI  - Spinal cord tachykinins in the micturition reflex.

PMID- 8552767
TI  - Neuropeptides in morphologically and functionally identified primary afferent
      neurons in dorsal root ganglia: substance P, CGRP and somatostatin.

PMID- 8552768
TI  - Electrophysiology of neuropeptides in the sensory spinal cord.

PMID- 8552769
TI  - Release of neuropeptides in the spinal cord.

PMID- 8552770
TI  - The peptidergic innervation of spinal motoneurons via the bulbospinal 5
      hydroxytryptamine pathway.

PMID- 8552771
TI  - Interaction of neuropeptides and excitatory amino acids in the rat superficial
      spinal dorsal horn.

PMID- 8552772
TI  - Peptidergic afferents: physiological aspects.

PMID- 8552773
TI  - Neuropeptides and spinal cord reflexes.

PMID- 8552774
TI  - Proto-oncogenes: basic concepts and stimulation induced changes in the spinal
      cord.

PMID- 8552775
TI  - Immediate early genes (IEGs) encoding for inducible transcription factors (ITFs)
      and neuropeptides in the nervous system: functional network for long-term
      plasticity and pain.

PMID- 8552776
TI  - Peptides in motoneurons.

PMID- 8552777
TI  - Neuropeptides in neuroblastomas and ganglioneuromas.

PMID- 8552778
TI  - Effects of ankle joint inflammation on the proportion of calcitonin gene-related
      peptide (CGRP)-immunopositive perikarya in dorsal root ganglia.

PMID- 8552779
TI  - Regulation of spinal neuropeptide genes in a rat model of peripheral inflammation
      and hyperalgesia.

PMID- 8552780
TI  - Prostaglandin-induced neuropeptide release from spinal cord.
AB  - The studies reviewed in this chapter present a convincing argument that
      prostaglandins have direct actions at the level of the spinal cord to enhance
      nociception. Furthermore, an increasing body of evidence supports the hypothesis
      that one important site of action of these eicosanoids is the terminals of
      sensory neurons. Studies performed in our laboratory add to this evidence by
      demonstrating that relatively large concentrations of prostaglandins increase SP
      release, whereas lower amounts augment the capsaicin-stimulated release of both
      SP and CGRP from rat spinal cord slices. In neuronal cultures of rat dorsal root
      ganglia, prostaglandins also facilitate the evoked release of SP and CGRP,
      indicating a direct action of these autocoids on sensory neurons. Based on these
      studies, it is interesting to speculate that the actions of prostaglandins on
      peptide release are one mechanism to account for hyperalgesia produced by these
      eicosanoids. In addition, by a sustained action, prostaglandins may contribute to
      the enhanced excitability of sensory neurons during inflammation. Indeed, our
      observations that intrathecal Ketorolac abolished the elevation in SP release
      during inflammation support this possibility. Whether the effect of the NSAID are
      caused by the inhibition of prostaglandin synthesis in the spinal cord are yet to
      be determined. Further work is necessary to establish a role for prostaglandins
      in the adaptive changes of nociceptive neurons that occur in chronic pain states
      and in inflammation. In addition, the cellular mechanisms underlying the effects
      of prostaglandins on sensory neurons are yet to be elucidated.

PMID- 8552781
TI  - The opioid receptor antagonist naloxone influences the pathophysiology of spinal
      cord injury.

PMID- 8552782
TI  - Influence of dynorphin A antibodies on the formation of edema and cell changes in
      spinal cord trauma.

PMID- 8552783
TI  - Organization of peptidergic neurons in the dorsal horn of the spinal cord:
      anatomical and functional correlates.

PMID- 8552784
TI  - Peptidergic neurons in the vertebrate spinal cord: evolutionary trends.

PMID- 8552785
TI  - Opioid receptors in the superficial layers of the rat spinal cord: functional
      implications in pain processing.

PMID- 8552786
TI  - Tachykinin receptors in the spinal cord.
AB  - In summary, all three tachykinin receptors appear to be important modulators of
      physiological systems in the spinal cord. However, although there is a good deal
      of data concerning binding characteristics in peripheral tissues, work done in
      the spinal cord is scanty, leading to a number of unanswered questions. Firstly,
      Lui et al. (1993) have suggested a discrepancy between the location of SP binding
      sites and SP containing terminals. This might explain the conflicting evidence on
      the role of NK1 receptors in the dorsal horn. Furthermore, evidence that NK2
      receptors are involved in nociception is increasing, however binding sites for
      these receptors in the spinal cord have not been demonstrated. This appears to be
      due to the difficulty in locating an ideal receptor specific ligand. The role of
      NK2 receptors in autonomic function is also unclear, perhaps for the same reason.
      Finally, there is evidence indicating that NK3 binding sites are increased
      following transection of the LIV-VI dorsal roots, however, studies on the effects
      of inflammation have not been done, as they have with the NK1 and NK2 receptors.
      All of these and many more unanswered questions require further investigation.

PMID- 8552787
TI  - Calcium channel antagonists in the treatment of coronary artery disease:
      fundamental pharmacological properties relevant to clinical use.
AB  - Calcium channel antagonists are a diverse group of drugs with clinical
      antianginal and antihypertensive properties. They have as a common property the
      capacity to lessen the rate of calcium ion entry through a specific type of
      calcium channel, namely the voltage-gated L-type channel. They do not bind to all
      the pore molecules; therefore, there is still some residual entry of calcium
      ions. Variables determining the clinical efficacy of the different drugs include
      the binding sites involved, the tissue specificity of the drug, the duration of
      action, and (closely related) the degree of counter-regulatory neurohumoral
      activation. Inhibitory effects on the calcium channels of vascular smooth muscle
      explain the antihypertensive effect and the reduction of afterload, one of the
      antianginal mechanisms common to all of the drugs. In general, the
      dihydropyridines, such as nifedipine, are more vascular-selective than the non
      dihydropyridines, such as verapamil and diltiazem. The latter owe part of their
      antianginal activity to more prominent effects on the calcium channels in the
      sinoatrial node (decreased heart rate) and the myocardium (negative inotropic
      effect). In addition, calcium channel antagonists are coronary artery
      vasodilators. Whether the latter effect confers on these drugs any specific
      advantage in the therapy of anginal syndromes is controversial.

PMID- 8552788
TI  - Calcium channel antagonists in the management of anginal syndromes: changing
      concepts in relation to the role of coronary vasospasm.
AB  - Despite the increasing evidence that alterations in coronary vascular tone can
      and do occur in patients with anginal syndromes, only in a minority of such
      patients with Prinzmetal's angina is there decisive evidence that the coronary
      vasodilation induced by calcium channel antagonists (CCAs) plays a specific
      therapeutic role. CCAs may also give therapeutic benefit in a number of
      conditions in which coronary vasoconstriction may contribute to ischemia, such as
      hyperventilation, cold-induced angina, or silent ischemia not caused by an
      increase in heart rate. Thus, the decision of whether or not to use CCAs in
      angina syndromes will often have to be made on grounds other than what appears to
      be a minor role of vasospasm in the overall spectrum of angina. There are
      preliminary indications that the long-term prognosis may be different among
      different categories of CCAs.

PMID- 8552789
TI  - Transesophageal echocardiography in critical care units: Henry Ford Hospital
      experience and review of the literature.
AB  - Transthoracic echocardiography is of limited value in intensive care units
      primarily because of mechanical ventilators, surgical wounds, and the inability
      to position the patient to his left side. Imaging from the transesophageal window
      overcomes these problems, resulting in good-quality study in these patients
      subsets. We performed both transthoracic and transesophageal echocardiography
      with color-flow Doppler tests in 121 patients in various critical care units. The
      transesophageal ultrasound test was valuable in identifying patients with
      suspected left-sided native and prosthetic valve vegetations, prosthetic mitral
      but not aortic valve regurgitation, native mitral and aortic valve pathoogy, and
      aortic dissection and in determining cardiac etiology of systemic emboli,
      hypotension, hypoxia, and heart failure. Based on transesophageal
      echocardiographic findings, additional information was provided in 38 (32%)
      patients, resulting in appropriate surgery in 22 instances. In conclusion,
      transesophageal echocardiography is a useful tool in evaluating critically ill
      patients.

PMID- 8552790
TI  - Thyroid hormone therapy in cardiovascular disease.
AB  - The relationship between thyroid disease states and cardiovascular hemodynamics
      is well recognized. Although the long-term effects of thyroid hormone are thought
      to result from changes in myocardial gene expression, attention has recently
      focused on acute, non-nuclear-mediated actions of L-triidothyronine (T3), the
      biologically active form of the hormone. Various lines of evidence have
      documented that T3 can act as a vasodilator and inotrope. With this recognition
      have come novel treatment strategies targeted at specific clinical conditions
      including heart failure and cardiac surgery that are associated with impaired
      cardiovascular performance and low serum T3 levels. An understanding of the
      mechanisms of action of thyroid hormone on the heart and peripheral vasculature
      is essential for the rational implementation of thyroid hormone as a therapeutic
      agent. As outlined in this review, initial clinical experience suggests that the
      ability of thyroid hormone to increase cardiac output and to lower systemic
      vascular resistance may provide a novel treatment option for physicians caring
      for patients with cardiovascular illness.

PMID- 8552791
TI  - Antithrombotic therapy in atrial fibrillation: a review of randomized trials with
      special reference to the Stroke Prevention in Atrial Fibrillation II (SPAF II)
      Trial.
AB  - Nonvalvular atrial fibrillation is common and is associated with a high risk of
      system embolism. Recently, several large randomized trials have been completed
      that have established the efficacy of antithrombotic therapy for both primary and
      secondary prevention of systemic thromboembolism with an acceptable rate of
      bleeding complications in these patients. This section of clinical trials review
      summarizes data from all published randomized trials of antithrombotic therapy in
      atrial fibrillation. The efficacy of aspirin versus warfarin is analyzed. The
      role of clinical and echo-cardiographic findings to stratify patients is also
      highlighted. The Stroke Prevention in Atrial Fibrillation II trial is discussed
      in detail.

PMID- 8552792
TI  - [Role of signal transduction mechanisms in light-induced entrainment of
      biological clocks].

PMID- 8552793
TI  - [Sidedness of biomembrane: asymmetrical distribution and flip-flop of
      phospholipids across lipid bilayer].

PMID- 8552794
TI  - [COP-coated vesicles in intracellular protein transport].

PMID- 8552795
TI  - [Structural and functional analysis of sialyltransferases: the dawn of new age
      for glycobiology].

PMID- 8552797
TI  - Behind the scenes.

PMID- 8552796
TI  - [Measurements of density and partial specific volume].

PMID- 8552798
TI  - A strategy to promote research-based nursing care: effects on childbirth
      outcomes.
AB  - Studies at area hospitals revealed many gaps between research evidence and
      intrapartum nursing practices. A randomized controlled trial involving 20
      hospitals was used to evaluate the effectiveness of a marketing strategy to
      promote research-based nursing care. It was hypothesized that the strategy would
      result in lower rates of epidural analgesia, through increasing the amount of
      support nurses provided to their patients. Other outcomes included rates of
      narcotic analgesia, episiotomy, and operative delivery. The marketing strategy
      was unsuccessful in improving intrapartum nursing care. Much more research is
      needed about the factors that facilitate improvements in nursing practice.

PMID- 8552799
TI  - The worksite environment as a cue to smoking reduction.
AB  - With a modified version of the Health Belief Model as the conceptual framework,
      the hypothesis that exposure to a worksite health-promoting environment acted as
      a cue to smoking reduction among 310 smokers was tested with a quasi-experimental
      design. Using path analysis (LISREL), the total effects on posttest smoking were
      decomposed. Results showed exposure to the health-promoting environment had
      statistically significant direct and indirect effects on posttest smoking. The
      indirect effect was through the posttest perceived barriers variable. The LISREL
      model explained 74% of the variance in smoking reduction and fit the data
      satisfactorily. The importance of developing the worksite as a health-promoting
      force is discussed.

PMID- 8552800
TI  - Coping with radiation therapy: optimism and the effect of preparatory
      interventions.
AB  - To test the hypotheses that pessimists might benefit from concrete objective
      information based on self-regulation theory and that optimists might benefit from
      instruction in self-care and coping based on self-care theory, 62 patients
      receiving radiation therapy (RT) for prostate cancer were studied. The two
      experimental and control intervention messages were given three times during RT.
      Mood and disruption of activities were assessed three times during and three
      times after RT. The self-care instruction had no effects on either outcome. The
      prediction from self-regulation theory was supported, in part, with concrete
      objective information having a positive effect on mood among pessimistic
      patients. Concrete objective information resulted in less recreation and pastime
      disruption in both optimistic and pessimistic patients at the times they
      experienced the most RT side effects.

PMID- 8552801
TI  - Sexual assault history and limitations in physical functioning in two general
      population samples.
AB  - The purpose of this study was to evaluate the functional impact of sexual assault
      history in two general population surveys (pooled N = 6,024). Sexual assault was
      associated with functional impairment regardless of gender, ethnicity, and study
      site. Repeated assaults, spousal assaults, physically threatening assaults, and
      those resulting in intercourse or sexual disturbances were most strongly related
      to impairment. The greater numbers of severe physical symptoms experienced by
      sexually assaulted persons accounted for their poorer functioning. Depression did
      not account for this association despite its mediating role. Physical symptoms
      and depression had similar relationships to functioning for assaulted and
      nonassaulted persons.

PMID- 8552802
TI  - Relationship between gastrointestinal and dysmenorrheic symptoms at menses.
AB  - The relationship between gastrointestinal (GI) symptoms and uterine cramping pain
      at menses, controlling for affective states and prostaglandin synthesis inhibitor
      use, was examined. A total of 53 women completed a daily diary of symptoms, stool
      characteristics, and medication use for three consecutive menstrual cycles. There
      were significant across-women and within-woman relationships between stomach
      pain, nausea, and uterine cramping pain, but not between cramping pain and
      constipation, diarrhea, or stool characteristics. These results support the
      presence of a similar mechanism in the generation of distressing GI symptoms and
      uterine cramping pain at menses.

PMID- 8552803
TI  - Women's work environment and health: clerical workers in Brazil.
AB  - Although women are participating more in the formal workforce, the majority are
      employed primarily in low-income and low-status occupations. While work roles may
      provide women with some rewards, employment may also create many stressful
      demands on their daily lives. As part of an international study, 60 female
      Brazilian clerical workers responded to a self-administered questionnaire
      describing what they liked, disliked, and found stressful about the structural,
      physical, and social aspects of their work environment. Participants also
      identified strategies they used to cope with stress in the work environment.
      Dimensions of healthy environments identified in the data included utility,
      challenge, participation, safety, pleasing workplace, valuation, clarity of
      roles, and empowerment. Unhealthy environments were characterized by hazards,
      bureaucracy, devaluation, and economic constraints. Participants described their
      concerns about the effect of the environment on their physical and mental health,
      but tended to adopt a passive, resigned coping style rather than a proactive
      approach to co-creating a healthier work environment. The results and their
      relationship to healthy work environments are discussed within the context of the
      larger sociopolitical environment of Brazil.

PMID- 8552804
TI  - Effects of work stressors and work climate on long-term care staff's job morale
      and functioning.
AB  - Relationships between work stressors and work climate, and job morale and
      functioning were examined. Initial and 8-month follow-up data were obtained from
      405 staff in 14 long-term care facilities. Relationship and workload stressors
      were related to less job satisfaction and intent to stay in the job, and more job
      related distress, depression, and physical symptoms. Patient care task stressors
      were associated with better outcomes. More positive work climates were linked to
      higher job morale. Initial work stressors predicted poorer functioning, and
      coworker cohesion predicted more intent to stay in the job at follow-up.

PMID- 8552805
TI  - An application of hierarchical linear models to longitudinal studies.
AB  - Nursing researchers are increasingly interested in studying changes in patients'
      outcomes, such as physiologic and psychological status, across time. The most
      frequently used approaches, univariate repeated measures, multivariate repeated
      measures, and pre- and posttest differences, have restrictive assumptions and
      unrealistic data requirements. Therefore, a more flexible approach is needed.
      Hierarchical linear models (HLM) can be used to solve these problems. The
      advantages of HLM are (a) it describes each individual's growth trajectory and
      its relationship with initial status, (b) it is not restricted by unrealistic
      assumptions, (c) if solves the commonly observed problems of missing data, (d) it
      does not require fixed time intervals, and (e) it provides more precise
      estimation.

PMID- 8552806
TI  - Re: Therapeutic touch...

PMID- 8552807
TI  - Re: Cole and Slocumb's response to "AIDS, nurses' intentions, and the
      interpretation of findings".

PMID- 8552808
TI  - [Medals that tell the history of Italian radiology].

PMID- 8552809
TI  - [Color Doppler ultrasonography of the scrotum].

PMID- 8552810
TI  - [Magnetic resonance in the evaluation of lesions of the posterior tibial
      tendons].
AB  - Posterior tibial tendon (PTT) tears are the most common cause of unilateral
      flatfoot in adults. It is a chronic pathologic condition with a degenerative
      inflammatory character which usually affects middle-aged or elderly women, with
      no history of trauma. PTT tears occur more rarely in young patients, after an
      acute traumatic event. Clinically, PTT tears present with pain along the tendon,
      increased by weight bearing, swelling and functional limitation. PTT tears are
      surgically classified in three types: with tendon hypertrophy, with tendon
      atrophy and with complete tendon tear. The three different anatomicosurgical
      patterns require different therapeutic approaches. This work was aimed at
      investigating MR capabilities in recognizing the direct and indirect signs of PTT
      tears, assessing MR sensitivity in different types of tears. Fourteen patients
      with clinically suspected PTT tears and 10 control patients underwent MRI of the
      ankle (0.5 T, GE Vectra) following a study protocol including SE T1-weighted and
      FSE T2-weighted scans acquired on the axial and sagittal planes. In all patients,
      the transverse diameter, the shape and the section surface of the lesions were
      calculated on the axial planes at different levels; all these parameters were
      compared with those of the adjacent tendons, i.e., flexor longus ditae and flexor
      hallucis. Moreover, the probable presence was investigated of intratendineous
      signal intensity changes, of peritendineous synovial fluid and of indirect signs
      of PTT tear, i.e., the lack of longitudinal talonavicular alignment and the
      bulging of the medial navicular tubercle. According to MR results, the 14
      patients were subdivided into 8 patients with type-I tears, 2 with type-II tears
      and 4 patients with type-III tears. The measures of healthy and injured tendons
      were in substantial agreement: in fewer cases, agreement was found also between
      symptomatic and control patients with intratendineous signal changes. Thus, the
      specificity of the two parameters was reduced. Finally, such indirect signs of
      PTT tear as a hypertrophic navicular tubercle and the lack of longitudinal
      talonavicular alignment exhibited good specificity, but sensitivity was barely
      sufficient. MR diagnoses were confirmed at surgery in 6 patients with type-II and
      type-III tears. In conclusion, MRI appears to be a suitable modality for
      recognizing and classifying PTT tears and a useful tool for the treatment and
      follow-up of these patients.

PMID- 8552811
TI  - [Medial luxation of the long head of the brachial biceps. Magnetic resonance
      imaging].
AB  - The medial intraarticular dislocation of the biceps tendon of the shoulder is a
      rare pathologic condition and its diagnosis before surgery is very important to
      properly repair the tears of rotator cuff tendons, the rotator cuff being nearly
      always involved. We report our experience in 8 patients (1.8%) with biceps tendon
      dislocation observed in a series of 432 patients submitted to MR studies to
      address several diagnostic issues. The MR patterns of biceps tendon dislocation
      and the related physiopathologic mechanisms are discussed. The MR images were
      retrospectively reviewed by two of the authors and dislocations were diagnosed in
      a subgroup of 34 patients (7.8%), associated with full-thickness tears of the
      tendon of supraspinatus muscle; all patients also presented a full-thickness tear
      of the subscapularis tendon. A dislocated biceps tendon can follow a variety of
      courses depending on the pattern of subscapularis tendon tear. We always found a
      complete dislocation of the biceps tendon; other dislocation patterns reported in
      the literature, and particularly oblique and superficial dislocations, were never
      observed in our series. Dislocation is visible on axial images, where the tendon
      appears completely displaced from the bicipital groove, but also sagittal and
      coronal images can depict the more medial position of the tendon. In our patients
      this abnormality was correctly identified in 4 patients during the first
      observation and in the extant patients during the retrospective review. The
      dislocation of the biceps tendon of the shoulder was frequently associated with a
      complete tear of the supraspinatus tendon (23.5%). All patients exhibited severe
      joint effusion and in two patients the dislodged tendon was also inflamed.

PMID- 8552812
TI  - [Clinical usefulness of a computerized tomography study of morphology of the
      femoral canal in patients candidates for hip prosthesis].
AB  - In the last few years hip arthroplasty has been increasingly used and both
      metaphysis and diaphysis of the proximal femur are studied preoperatively for
      best compliance between prosthesis and bone. Indeed, the best results can be
      obtained by reducing the risk of stem end mobilization, which means to choose the
      prosthesis fitting the femoral canal best and to limit the use of cement
      prostheses, which are at high risk of mobilization in time, to advanced
      osteoporosis patients. We used a simple and repeatable CT technique to study
      femoral canal structure and size. After accurately positioning the patients
      inside the gantry, we acquired some axial scans at scheduled levels referring to
      the horizontal midline of the lesser trochanter. The axial scans were acquired 2
      cm above and 5 and 10 cm below the horizontal midline in 105 patients.
      Measurements were bilateral in 13 patients. Finally, the results were compared
      with the surgical outcome. Femoral canal cross-diameters and cortical bone width
      varied greatly, which variations were confirmed in bilateral measurements and in
      the same patient between the two femurs. Femoral canal structure, which can be
      remodelled, influences the choice of the stem and thus the amount of cement. We
      believe this method to be fundamental for correct surgical planning and for best
      treatment outcome.

PMID- 8552813
TI  - [Combined diagnosis of breast cancer recurrences after conservative treatment.
      Critical review of 143 consecutive cases].
AB  - The diagnostic features are reported of 143 consecutive patients with breast
      cancer intramammary recurrences observed after conservative treatment, 1984 to
      1994. Disease-free interval after surgery was 3.7 years on the average, being
      longer for the patients receiving postoperative breast irradiation (3.9 vs 3.1
      years). The conserved breast was followed-up on a regular basis with palpation
      and mammography, whereas US and cytology were used only in selected suspicious
      cases. Palpation, mammography, cytology or US suspected the recurrence in 75, 64,
      81 and 77% of cases, respectively. Mammographic false negatives were not
      explained by breast parenchymal density (Wolfe's pattern) or by breast
      irradiation, but were likely to be ascribed to the masking effect of surgical
      scars and distortion. Most failures at cytology were caused by inadequate
      sampling: when sampling was adequate, cytology exhibited the highest sensitivity
      (97%). In all, combined palpation + mammography, palpation + cytology and
      palpation + mammography + cytology diagnosed correctly 97, 98 and 100% of cases,
      respectively. Palpation should be always combined with mammography in the follow
      up of the conserved breast, but US and aspiration cytology should be performed in
      case of any clinico-radiologic abnormality carrying even a minimal risk of
      recurrence.

PMID- 8552814
TI  - [Magnetic resonance and computerized tomography of posterior cranial fossa tumors
      in childhood. Differential diagnosis and assessment of lesion extent].
AB  - In the last thirty years much progress has been made in the treatment of brain
      tumors in children, thanks to modern diagnostic imaging techniques, together with
      neurosurgery and radiotherapy, for the diagnosis and follow-up of these lesions.
      MRI and paramagnetic contrast agents have revolutionized the imaging of
      intracranial conditions, especially in the posterior cranial fossa. The
      superiority of MRI over CT is well known and reported in the literature, but the
      adequacy of the two methods has rarely been compared. Therefore, this study was
      aimed at assessing and quantitating the accuracy of MRI and CT relative to two
      essential parameters: preoperative "histologic" diagnosis and local and distant
      intracranial tumor extent. In 52 selected patients the final histologic diagnosis
      was cerebellar medulloblastoma in 20 cases, cerebellar astrocytoma in 12 cases,
      brain stem glioma in 12 cases and ependymoma in 8 cases. CT allowed the correct
      diagnosis to be made in 25 patients (48%), with questionable findings in 21
      patients (40%) and 6 misdiagnoses (12%). MRI allowed the correct diagnosis to be
      made in 43 patients (83%), with questionable findings in 9 patients (17%) and no
      misdiagnoses. MRI depicted local and distant tumor spread in 34 patients while CT
      showed it in 22 patients only. The analysis of the results confirmed the
      superiority of MRI over CT, relative to the parameters considered, i.e. histology
      and the assessment of tumor spread. In the clinical suspicion of brain tumors of
      the posterior cranial fossa in children, MRI--if available--should be the
      examination of choice if the patient's clinical status does not prevent its use.
      CT should be used only in emergency cases (acute intracranial hypertension) to
      identify hydrocephalus and intratumoral hemorrhages. Unenhanced CT also yields
      useful pieces of information for lesion "histology" and may be used to integrate
      MR findings in selected cases.

PMID- 8552815
TI  - [Comparison of computerized tomography and magnetic resonance in staging of T and
      N parameters in head and neck neoplasms].
AB  - January 1990, through January 1994, eighty untreated patients with head and neck
      cancer were consecutively submitted to CT and MRI of the head and neck before
      surgery. CT and MR findings were then compared to operative histologic findings.
      Forty-eight of 52 T4 cases at CT were confirmed at surgery (89%), 7 of 13 T3
      cases at CT were also confirmed (54%), as well as 8 of 15 T2 cases (53%). CT
      understaged 13 cases (6 T3 and 7 T2), which surgery staged as T4, CT overstaged 4
      cases as T4, which were 2 pT2 and 2 pT3 at histology. All the 54 cases MRI staged
      as T4 were confirmed at surgery (100%), 3 of 12 MRI staged as T3 were pT4 at
      surgery (25%) and, finally, 4 of 14 cases MRI staged as T2 were pT4 at histology
      (28%). Only one case staged as pT4 at surgery and CT had been staged as T3 by MRI
      because the latter method had failed to depict hyoid involvement. On the other
      hand, in 6 cases MRI correctly modified CT staging. Overall CT accuracy was 79%
      and MR accuracy 91%. CT sensitivity was 70% versus 75% with MRI, specificity was
      80% versus 78%, respectively, and overall accuracy 75% versus 76%. Only in two
      patients MRI correctly modified CT staging (N1 at surgery). Our results confirm
      various advantages of MRI over CT in the assessment of tumor mass ("T"
      parameter), mainly in T2 and T3 cases, because MRI yields higher soft tissue
      contrast resolution and has multiplanar capabilities. CT was superior to MRI only
      in the assessment of bone involvement. This study also confirmed similar CT and
      MR capabilities in detecting lymph node tumor spread. Finally, MRI did not allow
      earlier detection of micrometastases than CT.

PMID- 8552816
TI  - [Imaging of the thymus gland in myasthenia gravis (computerized tomography and
      magnetic resonance)].
AB  - Since thymectomy is nearly always indicated as a possible treatment of myasthenia
      gravis, we examined with Magnetic Resonance (MRI) and Computed Tomography (CT) 22
      patients (21-62 years old) to identify the best methodological approach. MR
      images were obtained with a 1.5 T superconducting unit with slice thickness
      ranging from 6 to 8 mm and an interslice gap of 0.6 and 0.8 mm. Spin-echo images
      were acquired with repetition time (TR) < 700 ms and echo time (TE) of 20 ms and
      T2-weighted images with TR > 1800 ms and TE of 80 ms. The sections were obtained,
      with cardiac gating, on transverse and sagittal planes. CT was performed with
      contiguous 5-mm slice thickness, after intravenous bolus injection of contrast
      medium. All the patients underwent surgery of anterior mediastinum and histologic
      diagnosis was made. Both CT and MRI correctly identified the patterns of normal
      thymus or hyperplasia not associated with gland enlargement, the only two cases
      of hyperplasia with thymic enlargement and clearly demonstrated thymomas. MRI
      appears to be more accurate in the evaluation of the relationship between thymus
      and contiguous structures. If pericardial infiltration is suspected, sagittal MR
      scans yield accurate information on tumor spread. We recommend MRI of anterior
      mediastinum to rule out the presence of a thymoma and the possible involvement of
      contiguous structures.

PMID- 8552817
TI  - [Evaluation of total and inflated lung volumes by a quantitative study using
      computerized tomography in patients with acute noncardiogenic pulmonary edema
      (ARDS)].
AB  - Our study was aimed at developing a method to assess lung volumes and relative
      percentages of well-inflated lung parenchyma in Adult Respiratory Distress
      Syndrome (ARDS) patients by processing conventional CT examinations of the lung
      and at investigating the prognostic value of CT findings. Fourteen patients (5
      women and 9 men, age range: 35-79 years) admitted to the intensive care unit
      January, 1992, to June, 1994, because of severe ARDS, and with lung injury scores
      exceeding 2.5, were submitted to CT. A homologous group of 14 patients matched
      for sex and age and with normal lungs was examined as a control group to
      investigate the accuracy of our method. Two examinations were obtained in 7 of 14
      ARDS patients; the trend of lung volumes and of the relative rates of well
      inflated parenchyma could thus be calculated. During the examination, we
      maintained in all ARDS patients the same ventilatory pattern used in the
      intensive care unit. Consequently, in 18/21 examinations scans and respiratory
      phases were not correlated. In the control group no statistically significant
      differences were observed between the scans obtained with (inspiratory apnea) and
      without coordination with the respiratory phase. As for lung volumes, our results
      in normal subjects showed a good correlation with normal spirometric data. In
      ARDS patients lung volumes, although reduced, did not correlate with prognosis.
      As for the percentage of well-inflated parenchyma in ARDS patients, we observed a
      good correlation with prognosis in the patients submitted to two examinations
      and, in all patients, a good correlation with D(A-a)O2 index (p < 0.05),
      PaO2/FiO2 index (p < 0.005) and with the rate of arteriovenous shunt (p < 0.001).
      In conclusion, our results show that CT of the lung is a reliable and repeatable
      method for the functional assessment of the lung in ARDS patients.

PMID- 8552818
TI  - [Radiography and computerized tomography of the thorax in lung small cell tumors.
      Diagnostic possibilities].
AB  - Small cell lung cancer (SCLC) is a highly malignant tumor which is nearly always
      metastatic at diagnosis and generally staged as a localized or diffuse disease.
      The authors compared the capabilities and the advantages of CT with those of
      chest films in the diagnosis, staging and follow-up of this type of cancer in 54
      patients (52 men and 2 women, mean age: 62 years, range: 45 to 79 years). All the
      patients were submitted to the same examinations 3 months (18 patients), 6 months
      (6 patients), 9 months (6 patients) and 12 months (2 patients) after
      radiochemotherapy. Median survival time was 13 months (range: 6-20 months). On
      staging, radiography showed mediastinal masses (63%), bronchial narrowing (57%),
      hilar masses (45%), atelectasis (37%), pleural effusion (29%), pericardial
      thickening and/or effusion (22%), multiple (20%) or single (16%) peripheral
      masses and tracheal narrowing (2%). CT was more sensitive, chiefly in depicting
      mediastinal masses (34 cases demonstrated by CT vs 12 by chest films), bronchial
      narrowing (38 vs 0) and pericardial involvement (12 vs 0); after CT, 12 patients
      with localized disease on chest films were diagnosed as having diffuse disease.
      Complete response after therapy, i.e., the total disappearance of all signs and
      symptoms of disease for 30 days at least, was depicted by CT in 16 patients and
      by chest films in 9 patients. Partial response-i.e., disease decrease by 50% or
      more, with no new lesions, for 30 days at least--was depicted by CT in 16
      patients and by chest films in 4 patients. Finally, no response or disease
      progression was depicted by CT in 10 patients and by chest films in 9 patients.
      To conclude, the presence of mediastinal and hilar masses, with bronchial
      narrowing, atelectasis, pleural/pericardial involvement, sometimes with a
      peripheral mass, are strongly suggestive of small cell lung cancer. CT was more
      sensitive than chest films in the staging of localized and diffuse disease, but
      it failed nevertheless to improve significantly the diagnosis, prognosis and
      follow-up of SCLC relative to chest films (p = 0.34).

PMID- 8552819
TI  - [Congenital anomalies of the inferior vena cava: role of imaging].
AB  - In recent years, clinics and radiology of congenital anomalies of the inferior
      vena cava have increased in importance in planning abdominal surgery, liver or
      kidney transplantation, or new interventional or diagnostic procedures such as
      the positioning of inferior vena cava filters to prevent pulmonary embolism,
      varicocel sclerotherapy and renal venous sampling. In the past, the radiologic
      assessment of these rare anomalies was performed only with angiography, which
      remains the most accurate diagnostic method. Today, besides angiography, less
      invasive examinations can be performed, e.g., US, CT and MRI, with MRA. In the
      last two years, 5 patients with inferior vena cava anomalies were examined: 3 had
      double inferior vena cava and 2 azygos continuation. All of them were submitted
      to US, CT, MRI and MRA and 3 patients underwent also angiography, two of them
      with double puncture. US can suggest the diagnosis but may be limited by
      technical factors and in the assessment of the whole inferior vena cava. Enhanced
      CT can depict anomaly extent, but uses contrast agents and ionizing radiations.
      Angiography better depicts craniocaudal spread and collateral networks but is an
      invasive procedure and sometimes needs a double puncture (double inferior vena
      cava). MRI, with MRA, yields the same information as the other modalities, but
      without contrast agents or ionizing radiations. The development of velocity
      encoded sequences will probably make this technique the method of choice in the
      study of inferior vena cava anomalies. Our study was aimed at reviewing the
      embryo-genesis of inferior vena cava anomalies and to assess the relative
      importance of different diagnostic procedures in the diagnosis and staging of
      these anomalies.

PMID- 8552820
TI  - [Magnetic resonance with endorectal coil in the locoregional staging of rectal
      carcinoma].
AB  - The accurate locoregional staging of rectal cancer is important in choosing and
      planning therapy. The diagnostic contribution of endorectal ultrasonography and
      of Computed Tomography is well known because both methods have been widely used
      in the last ten years. More recently, Magnetic Resonance Imaging (MRI) has been
      introduced in the preoperative staging of rectal cancer: most interestingly, in
      the last three years endorectal surface coils have become available as a clinical
      device. February through November, 1994, twenty patients affected with rectal
      carcinoma were examined with endorectal MRI. In order to assess their accuracy,
      MR staging results were compared with pathologic findings. MRI was performed with
      an 0.5 T system equipped with an endorectal surface coil. In all cases T2
      weighted turbo spin-echo sequences were performed on axial and sagittal or
      coronal planes. Rectal wall layers were reliably demonstrated in all patients.
      The comparison with pathologic findings showed 78.9% MR accuracy in assessing
      tumor infiltration depth. In addition, the study of perirectal lymph nodes showed
      83.2% MR sensitivity and 53.8% MR specificity. The high resolution images
      obtained using endorectal surface coils and the well-known panoramic capabilities
      of this method reveal MR potentials in rectal carcinoma staging.

PMID- 8552821
TI  - [Magnetic resonance cholangiopancreatography. A new method of noninvasive
      biliopancreatic diagnosis].
AB  - Magnetic Resonance cholangiopancreatography (MRCP) is a new noninvasive imaging
      technique for the visualization of the biliary ducts with cholangiographic images
      similar to those obtained with ERCP and PTC, but with no contrast agent
      injection. In this paper, we report on our preliminary experience with a mild
      field strength magnet (0.5T) and TSE sequences, acquired with respiratory
      compensation. The images were compared with ERCP images to compare diagnostic
      quality. Eighteen patients were examined: the biliary tract was dilated because
      of chronic pancreatitis in 3 patients, because of choledochal stones in 9, of
      carcinoma of the pancreatic head in 4, of lymphadenopathy in one patient. A
      patient submitted to choledochoduodenostomy and waiting for cholecystectomy was
      also examined. MRCP was performed with a superconductive magnet at 0.5T.
      Volumetric images on coronal planes were acquired; a T2-weighted TSE sequence (TR
      = 5000, TE = 244, Nex = 4, ETL = 45; acquisition time = 14 min 10 s) with
      respiratory compensation was also performed. The images were reconstructed on
      coronal planes at different angles with the MIP algorithm. All patients were then
      submitted to ERCP and one to PTC. In all patients, the intrahepatic biliary
      tracts, hepatic ducts and choledochus were completely demonstrated, with very
      good image quality in 16 cases and good in 2. The Wirsung duct was always
      visualized in all the 9 patients with mild to severe dilation. In conclusion,
      MRCP can be considered a valuable alternative to diagnostic ERCP. Further studies
      are necessary for better assessment of the potential advantages and pitfalls of
      this technique.

PMID- 8552822
TI  - Comparison of preoperative imaging techniques (thallium technetium scan and
      ultrasonography) and intraoperative staining (with methylene blue) in localizing
      the parathyroid glands.
AB  - We carried out a prospective study to compare the predictive value of
      preoperative thallium technetium scan, ultrasound (US) and intraoperative
      staining of the parathyroid glands (with methylene blue) in patients with
      parathyroid adenoma, parathyroid hyperplasia, thyroid carcinoma and
      thyrotoxicosis, in the Istanbul School of Medicine, Department of General
      Surgery. Methylene blue was given at a dose of 5 mg/kg/body weight in a 500 ml 5%
      Dextrose +0.9% saline solution 1 hour before surgery. All adenomas (10 patients),
      hyperplastic parathyroid glands (12 patients) and 45 of 52 suppressed glands
      (82%) were stained. In patients with thyroid carcinoma (7) and thyrotoxicosis
      (5), 42 of 48 normal parathyroid glands (87%) were stained. There were no
      maneuver-related complications. Thallium technetium scan (TT) accurately
      identified 10 of 10 (100%) parathyroid adenomas and 13 of 26 (50%) hyperplastic
      parathyroid glands. US successfully localized 10 of 10 (100%) adenomas and 18 of
      26 (66%) hyperplastic glands. Neither technique was successful in identifying
      normal glands. The intraoperative identification of the parathyroid glands with
      methylene blue was found to be an effective, safe and cost-effective technique
      which helps the surgeon in the dissection and shows abnormal parathyroid glands
      more accurately than preoperative imaging techniques.

PMID- 8552823
TI  - [Bulky mediastinal lymphomas: role of magnetic resonance and SPECT-Ga-67 in the
      evaluation of residual masses].
AB  - A residual mediastinal mass is a common finding during and/or after treatment for
      bulky mediastinal lymphoma and represents a difficult diagnostic problem. For
      correct therapy modulation, fibrosis must be distinguished from active disease.
      To assess diagnostic imaging potentials in the characterization of residual
      masses, 41 patients with bulky mediastinal lymphoma were examined with CT, MRI
      and Ga67-SPET; 92 examinations were performed for each technique: 14 before
      treatment, 42 during and after chemotherapy, 13 after radiotherapy and 23 six
      months after the end of treatment. CT provides useful pieces of information on
      tumor size but fails to depict tissue changes: therefore, only MR and SPET
      results were considered and compared with clinico-biological and follow-up
      findings. MRI and SPET were often in agreement with each other (78/92 cases) and
      with clinical data (98.7%); each examination yielded only one false positive. In
      case of disagreement (14/92 patients), MRI yielded more false-positive findings
      because it failed to differentiate neoplastic tissue from treatment-related
      conditions, i.e., granulation tissue, inflammation, necrosis, early fibrosis. In
      contrast, negative MR results were more reliable, MR negative predictive value
      being 100%. Ga67-SPET exhibited high sensitivity (97.1%) and specificity (91.2%),
      with fewer false positives than MRI (5 vs. 10). In conclusion, both examinations
      were accurate in the characterization of residual mediastinal masses during and
      after therapy, but MRI had higher sensitivity and Ga67-SPET higher specificity.
      Therefore, the authors acknowledge the complementary role of these two techniques
      and the necessity of an integrated approach, i.e., combined MRI and Ga67-SPET or
      CT and Ga67-SPET.

PMID- 8552824
TI  - [Treatment of superior vena cava syndrome by metal stents. Preliminary
      experience].
AB  - This study was aimed at verifying the feasibility of stent placement in superior
      vena cava syndrome (SVCS). From April, 1993, to February 1995, fifteen patients
      (12 men, 3 women, age range: 48-72 years, average age: 58 years), were treated
      for malignant stenoses involving superior vena cava in 9 cases, right innominate
      vein in 3, left innominate vein in 2 and subclavian veins in 1. All patients had
      been submitted to CT angiography and digital venography to assess side, length
      and type of the stenosis. In 6 patients locoregional fibrinolysis (with
      urokinase) was performed. The stenosis was successfully dilated by balloon
      catheter and the stent was finally removed. Subclavian and innominate veins
      stenoses were treated with Wallstent, using brachial approach, while stenoses of
      superior vena cava required transfemoral catheterization for Gianturco-Rosch "Z"
      stent placement. A control venogram was performed after stenting, with the
      evaluation of pre/post stent pressure gradient, and later at 1, 3 and 6 months.
      The stents were positioned in all patients with immediate technical success; no
      major complications occurred. Two recurrences were successfully resolved.
      Radiation and/or medical therapy without vascular disobstruction showed worse
      results in the treatment of superior vena cava syndrome. The percutaneous
      placement of self-expandable stents should be not only the therapeutic
      alternative to surgery but the method of choice in these pathologic conditions.

PMID- 8552825
TI  - [Therapy of malignant hepatic tumors using percutaneous hot saline injections.
      Feasibility study and preliminary results].
AB  - PURPOSE: To investigate the feasibility and the results of percutaneous hot
      saline injection therapy (PSIT) of liver tumors. MATERIAL AND METHODS: Eight
      patients with hepatocellular carcinoma (11 nodules), 1 with cholangiocarcinoma
      and 1 with a metastasis from colon cancer underwent PSIT. The patients were
      selected according to variable criteria; thus, each patient was considered apart.
      A boiling saline solution was injected into the hepatic lesions through a needle
      like those commonly used for percutaneous ethanol injection (PEI). The results
      were assessed with US, CT, angiography, the measurement of tumor marker levels,
      the histopathologic examination of needle biopsy material, resected specimens,
      explanted liver material and follow-up. RESULTS: PSIT was more easily performed
      and altogether better accepted than PEI; in particular, pain immediately
      regressed upon infusion interruption. For this reason and for the atoxicity of
      the injected liquid, relatively large lesions could be treated with a greater
      volume per session and fewer sessions than with PEI. Treatment outcome was
      positive in all patients, except for the cholangiocarcinoma patient who required
      surgery. The only major complication was moderate peritoneal bleeding in a
      patient with severe coagulopathy. CONCLUSION: PSIT can be considered a useful
      tool for the local treatment of hepatic tumors. Its systematic use to treat
      hepatocellular carcinoma must be proceeded by further comparative studies with
      PEI.

PMID- 8552826
TI  - [Use of CT-guided metal wires in pre-thoracoscopic localization of peripheral
      pulmonary nodules].
AB  - The recent developments in thoracic surgery have broadened the application
      spectrum of thoracoscopy. Video-assisted thoracoscopic lung resection is now
      available both to diagnose and to treat peripheral pulmonary nodules. A major
      factor limiting the success of thoracoscopic lung resection is the difficult
      localization of the pulmonary nodule. When lesions are very small and deep inside
      the lung, their preoperative detection may be difficult. This study was aimed at
      investigating the effectiveness of hookwires for CT-guided localization of
      peripheral pulmonary lesions requiring thoracoscopic resection. In 12 patients 12
      nodules, previously detected with chest radiography, were localized with
      hookwires under CT guidance. Ten of 12 patients underwent thoracoscopic resection
      for diagnostic purposes, while the extant two patients underwent therapeutic
      wedge resection. In all patients prethoracoscopic hookwire positioning was
      successful. In 11 of 12 patients the lesion was accurately localized, while in
      the extant patient the wire tip was inserted deeper than the nodule. In 3
      patients the wire was dislodged before surgery: in all of them a small hemorrhage
      developed on the visceral pleura and wedge resection was likewise possible. Four
      patients had a small pneumothorax which was not treated before surgery. In
      conclusion, percutaneous hookwire localization of peripheral lung lesions is an
      easy and efficacious technique and promotes thoracoscopy as a less invasive
      alternative to thoracotomy.

PMID- 8552827
TI  - [Ethical and legal considerations on informed consent in radiotherapy].

PMID- 8552828
TI  - [Esthetic results of the conservative treatment in breast carcinoma].
AB  - To assess the factors affecting cosmetic results after conservative breast cancer
      treatment, the findings of 164 patients submitted to conservative surgery plus
      radiotherapy 1988 to 1992, were reviewed. Surgery, except for one wider excision,
      consisted in quadrantectomy; the whole breast was given 50 Gy with telecobalt
      therapy and the 10-Gy boost on the surgical bed was administered with a Roentgen
      therapy unit. In 119 patients hormone therapy and/or chemotherapy were combined.
      The middle and median follow-up rates were 43.2 and 38 months, respectively.
      Outcomes were graded as excellent, satisfactory and poor (on the basis of
      asymmetry, volume loss and nipple retraction) and correlated with the Stepwise
      Logistic Regression method with patients' age, tumor size and site, combined
      chemotherapy and/or hormone therapy, surgical technique (axillary "en bloc"
      dissection) and surgery department. Lower external quadrant site, surgery
      department and some combined treatments (CMF and anthracycline plus Tamoxifen)
      bore a major influence on prognosis. Lower external quadrant site as a factor
      influencing treatment outcome is not reported in similar literature studies.
      Different treatment results in different surgery departments are certainly not
      related to different surgical techniques. The influence of combined adjuvant
      treatments on cosmetic results, related to the interaction with radiation damage
      repair, may worsen the cosmetic result, which is one of the main goals of
      conservative treatment. We hope that the whole treatment course (surgery,
      irradiation, medical treatment) can be customized to lesion characteristics and
      to patient's needs.

PMID- 8552829
TI  - [Symptomatic os odontoideum in a patient with Down's syndrome. A case report and
      review of the literature].

PMID- 8552830
TI  - [Echographic and magnetic resonance aspects in a case of bacterial myositis in
      AIDS].

PMID- 8552831
TI  - [Myositis ossificans circumscripta: computerized tomography and magnetic
      resonance findings].

PMID- 8552832
TI  - [Anomalous presentation of 2 cases of pulmonary carcinoma: obstructive jaundice
      and pancreatitis caused by pancreatic metastasis].

PMID- 8552833
TI  - [Azygos continuation of the inferior vena cava. A case report].

PMID- 8552834
TI  - [Intestinal invagination in adults. Apropos of 2 cases].

PMID- 8552835
TI  - [Leiomyoma of the jejunum. The role of selective angiography. A case report].

PMID- 8552836
TI  - [Breast juvenile fibroadenoma with myxoid features appearing after liver
      transplantation. A case].

PMID- 8552837
TI  - [Polyps of the posterior urethra in children. A case report and a proposal of a
      new diagnostic algorithm].

PMID- 8552838
TI  - [Echography and magnetic resonance using gadolinium in a case of benign
      schwannoma of the sciatic popliteal nerve].

PMID- 8552839
TI  - [Congenital rubella: a case of particular radiological value].

PMID- 8552840
TI  - [Post-traumatic hemorrhage of the right adrenal gland with late clinical onset. A
      case report].

PMID- 8552841
TI  - [Influence of environmental factors on the size of Musca domestica L. (Diptera:
      Muscidae)].
AB  - The nature and the magnitude of variability in 13 wing morphological characters
      of Musca domestica and the influence of environmental factors that could
      contribute to the occurrence of these variations were studied. Size and sexual
      dimorphism accounted for most of the total variation (83.7%). Variability caused
      by shape, which has a large genetic background, represents only 6.5% of the total
      variability. Males are usually smaller than females and both vary in a similar
      way throughout the year. Larval rearing density explains 93% of size changes.

PMID- 8552843
TI  - Sensitivity of animal-derived Trypanozoon stocks from sleeping sickness endemic
      foci of Nigeria to trypanocides and human plasma.
AB  - Twelve Trypanozoon stocks isolated from semi-nomadic cattle in known sleeping
      sickness foci of central and northern Nigeria were studied in terms of
      susceptibility to two trypanocides, diminazene aceturate (Berenil) and
      isometamidium chloride (Samorin) and human plasma. In infected small ruminants,
      three of the stocks were resistant to diminazene aceturate at does of 7.0 -14.0
      mg/kg body weight (b.w.) while isometamidium chloride at doses of 1.0 mg/kg b.w.
      or higher failed to effect parasitological cure of infections with two of the
      diminazene-resistant stocks. The two isometamidium-resistant stocks were also
      consistently resistant to the trypanolytic action of human plasma. It is
      suggested that cattle are reservoirs of Trypanosoma brucei subspecies potentially
      infective to man and resistant to the therapeutic action of the known sanative
      pair (diminazene and isometamidium).

PMID- 8552842
TI  - [Main infectious agents involved in the etiology of lung diseases of small
      ruminants in northern Cameroon].
AB  - Between 1990 and 1992, 91 necropsies of small ruminants affected with pulmonary
      illness led to the isolation of the following strains of Mycoplasma (M.): M.
      mycoides subsp. mycoides LC, M. ovipneumoniae, M. agalactiae, M. sp. type D2 and
      M. arginini. Eleven Pasteurella multocida strains (serotypes A1, A3, A5, A7 and
      D2) and 11 Pasteurella haemolytica strains (serotypes 1, 2, 3, 6, 7, 8 and 9)
      were isolated. Corynebacterium pseudotuberculosis, Actinomyces pyogenes,
      Staphylococcus sp., Streptococcus sp., Bacillus sp. and Mycobacterium sp. were
      also isolated. Thirty-two antibiograms were performed on Pasteurella,
      Corynebacterium pseudotuberculosis and Actinomyces pyogenes strains. Eighty eight
      p. cent were sensitive to penicillin G and oxytetracycline, and 84% to
      chloramphenicol; 50% were not sensitive to spiramycin and 47% to streptomycin.
      One Capripoxvirus strain was isolated on sheep. Pest of small ruminants (PPR)
      virus was detected by immunocapture ELISA test performed on some lung samples.
      Two serological surveys, one for contagious caprine pleuropneumonia (898 goats),
      between 1991 and 1993, and one for PPR (902 sheep and goats) in 1993, were
      conducted in the North and Far North provinces. No antibody against contagious
      caprine pleuropneumonia was detected. Among the animals in the sample, PPR
      prevalence was 64 +/- 7% in the Far North province and 14 +/- 3% in the North
      province. Concerning control measures, a vaccination campaign against small
      ruminant pasteurellosis appears to be hardly feasible because of the antigenic
      diversity of the isolated Pasteurella strains. PPR is endemic especially in the
      Far North province. The efficiency of a vaccination campaign against PPR must be
      estimated with a field survey.

PMID- 8552844
TI  - [Trypanosoma congolese in different species of horse flies (Diptera: Tabanidae)
      in Burkina Faso].
AB  - Four out of six Azawak zebu bulls raised in northern Burkina Faso were found to
      be infected with trypanosomes, including Trypanosoma congolense, six months after
      they had been transferred, uninfected, to the CIRDES experimental farm at
      Banankeledaga (Southwest Burkina Faso). Entomological surveys are carried out
      regularly in the area around this farm but, in one year, only 10 tsetse flies
      were captured, none of which showed infection in the midgut. However, a large
      number of tabanids were captured in the Glossina traps and dissection of some of
      them showed the presence of trypanosomes in their midgut. DNA amplification with
      the polymerase chain reaction (PCR) technique showed that the trypanosomes found
      in two tabanids belonged to the savannah type of T. congolense.

PMID- 8552845
TI  - The gastro-intestinal helminth infections of domestic fowl in Dschang, western
      Cameroon.
AB  - Three hundred and fifty one chickens purchased from the Dschang animal market
      were examined for gastro-intestinal helminths. Ten species were found with the
      following prevalences: Heterakis brevispiculum (59.3%), Ascaridia galli (51.6%),
      Hymenolepis carioca (48.4%), Dispharynx spiralis (20.8%), Tetrameres americana
      (17.1%), Amoebotaenia cuneata (15.1%), Raillietina tetragona (14.5%), Syngamus
      trachea (13.7%), Hymenolepis cantaniana (5.7%) and Capillaria contorta (2.0%).
      Infections were predominantly mixed (93.5%). The infection rates were not
      influenced by host sex except for A. galli which was more prevalent in cocks.
      Older chickens showed some resistance to A. cuneata and S. trachea. Parasite
      prevalence and/or worm burdens were generally higher during the rainy season
      (April to October).

PMID- 8552846
TI  - [Improving the salivation technic in the tsetse fly for the detection of
      infective metatripanosomes: study of the effect of biologic and non-biologic
      factors in the probing behavior of the tsetse fly].
AB  - The probing and salivation behaviour on a warm slide of three tsetse fly species
      or subspecies (glossina morsitans morsitans, Glossina palpalis gambiensis,
      Glossina tachinoides) was examined with respect to various parameters (species,
      sex, age, starvation period, trypanosome infection, quality of support). Each fly
      was given the opportunity to probe the warm slide (38 degrees C) for 5 minutes
      (we mean by probing an attempt to touch the glass slide by the proboscis in a
      biting position). G.m morsitans is by far the most efficient at probing (70.50%)
      when compared with G. tachinoides (50.50%) and G. palpalis gambiensis (45.80%).
      Globally, males (61.30%) are more active than females (52%) and those of the
      morsitans group are more active than those of the palpalis group. Teneral flies
      probe more easily than non-teneral flies, with an increased advantage in G. m.
      morsitans. The starvation period increases the probing behaviour, but at 48 h. G.
      m. morsitans probed as much as G. palpalis gambiensis and G. tachinoides at 72 h.
      The males of G. m. morsitans and G. palpalis gambiensis are more precocious than
      females, but the inverse is observed in G. tachinoides. Infection by T.
      congolense (EATRO 325 strain) does not affect the probing behaviour of males of
      all 3 species but seems to lower that of females in the palpalis group. Addition
      of a drop of PSG or blood improves the probing behaviour of infected G. m.
      morsitans females (the only ones tested). The results are discussed in relation
      to biological data and knowledge of the receptor systems of tsetse flies.

PMID- 8552847
TI  - [Control by traps of Glossina fuscipes fuscipes for protecting livestock in
      Central African Republic. IV. Entomological, parasitological and zootechnical
      impact].
AB  - Neighteen Mbororo zebu herds were monitored to evaluate the impact of a trapping
      campaign against Glossina fuscipes fuscipes restricted to the watering places.
      This programme is part of the strategy of an integrated campaign against bovine
      trypanosomoses in the Central African Republic. Trapping reduces the densities of
      G. f. fuscipes and causes trypanosome prevalence to fall. These effects are shown
      by the improved hematocrit values and the reduced number of trypanocidal
      treatments administered. The impact on productivity is more difficult to assess
      over a short period; nevertheless, it seems clear from the parameters calculated.

PMID- 8552849
TI  - ["Health in France": the merits of one report].

PMID- 8552848
TI  - [Standardization and evaluation of a manual salivation method for the detection
      of Trypanosoma infection in the tsetse fly (Diptera: Glossinidae)].
AB  - Two methods of salivation of tsetse flies, namely manual salivation and method of
      Bruce et al. were simultaneously evaluated on 1,702 male uninfected Glossina
      palpalis palpalis (Zaire), G. palpalis gambiensis (Bobo-Dioulasso), G. p.
      gambiensis (Maisons-Alfort) et G. morsitans morsitans (Mall) fasted for 23, 48
      and 72 hours. The risk of salivation was 0.66 by the manual method and 0.01 by
      the method of Bruce et al. The manual salivation method was standardised on 79
      male G. m. morsitans (Mall) infected with Trypanosoma congolense IL 1180. By this
      method, 70.88% of flies carrying mature and/or immature infection were
      identified. A clear difference was observed in the proportion of tsetse flies
      which salivated after 72 hours and those which salivated after 48 and 24 hours of
      fasting.

PMID- 8552850
TI  - [Monitoring neurotoxic effects among laboratory personnel working with organic
      solvents].
AB  - The relationship between organic solvent exposure and central nervous disorders
      make early detection of neurophysiologic et neuropsychologic alterations in
      organic solvent exposed workers a priority. Moreover, the variability in the
      frequency of exposure and the numerous organic solvents encountered in scientific
      laboratories render the environmental and biological measurements used in medical
      surveys almost impossible. The present study was undertaken to appreciate the
      potential neurotoxic effects of organic solvents handling in laboratory
      employees. Neurophysiological and neuropsychological tests batteries were used
      with each worker and data were adjusted for potential confounding factors (age
      and education level). A Principal Components Analysis were performed to reduce
      the information and the first five factors corresponded to: mood states, speed
      coding, contrast vision in high frequencies, manual dexterity and contrast vision
      in low frequencies. These five factors were compared between the daily
      manipulators of at least one solvent (n = 75) and the non or occasional solvent
      users (n = 35). The results from this study showed that subjects directly in
      contact with solvents had a poorer mood state than those who were not or rarely
      exposed (p < 0.01) and that independently of the "work activity". Mood state
      impairment in chronic solvent exposed workers has been shown by many authors,
      with or without psychomotor alteration, and may reflect possible over-exposure.
      Detection of this instability may lead to early neurophysiologic alteration in
      exposed workers and permit health services to intervene before the development of
      irreversible effects.

PMID- 8552851
TI  - Disagreement between hospital medical records and a structured patient interview
      on the type and date of the first symptom in cancers of the digestive tract.
AB  - Medical records have often been found to be less reliable than interviews to
      patients when data on the initial signs and symptoms of cancer, and the out-of
      hospital diagnostic process are sought; in spite of this, a large body of
      research on "diagnostic delay" in cancer is based on clinical records. As part of
      a study on delay in neoplasms of the digestive tract we analyzed the agreement on
      the type and date of the initial symptom between hospital records and a
      structured personal interview. Records were abstracted for a random sample (N =
      60) of 183 patients interviewed. Concordance on the date of the first symptom was
      deemed to exist if the difference was +/- 30 days. The Kappa index (kappa) and
      the overall proportion of agreement (with its corresponding 95% confidence
      interval) were used. Medical records and structured personal interviews were
      concordant on the type of the first neoplastic symptom in only 61% of cases
      (kappa = 0.50): 67% in esophagus cancer (kappa = 0.49), 60% in stomach cancer
      (kappa = 0.52), and 61% in colorectal cancer (kappa = 0.50). Records
      underestimated the occurrence of anorexia as first symptom and overestimated
      weight loss and dysphagia. Only 56% of cases were date-concordant, the agreement
      being lower in colorectal cancer (46%) than in esophageal (67%) and stomach
      cancer (75%). Records indicated the first symptom to have occurred at a later
      date than interviews in 33% of cases; overall, a study based on hospital records
      would have underestimated the symptom to diagnosis interval by 2.2 months per
      patient. Only 40% of cases were totally (symptom and date) concordant. Marked
      discrepancies may exist between the information contained in medical records and
      what patients report during a structured interview. The quality of medical
      records data on the duration and nature of cancer symptoms should be assessed
      before its use in etiologic and evaluative research.

PMID- 8552852
TI  - Education program for general practitioners on breast and cervical cancer
      screening: a randomized trial. PRE.SA.GF Collaborative Group.
AB  - This study was aimed at evaluating the effects of an education program for
      general practitioners on their prescribing behaviour for cervical and breast
      cancer screening tests, and assessing the feasibility of general practitioners
      participation in screening programs. All three cytology laboratories and 19 of
      the 20 radiologists in one administrative region ("Haute-Savoie") in France
      agreed to participate. The 278 general practices in this region were randomly
      assigned to either the intervention group (a one-day seminar on screening for
      breast cancer and cervical cancer) or the control group (n for both = 139). The
      prescriptions of tests for the following year were noted from the laboratories'
      and radiologists' records. No significant differences were observed between the
      intervention group and the control group for the number of mammographies
      prescribed with a mean of 19.3 and 15.2 per practice, respectively. However,
      significantly more mammographies were prescribed in women aged over 50 by the
      intervention group (p = 0.038). Inversely, fewer smear tests were prescribed in
      the intervention group (mean per practice: 40.5 and 46.1, respectively). A
      significantly higher number of practices in the intervention group did not
      prescribe any smear tests (p = 0.007). This study suggests that it is possible to
      influence general practitioners' participation in screening programs, but that
      the messages should be carefully presented, since negative effects are possible.

PMID- 8552853
TI  - [Life style and health behavior of southern European and North African immigrants
      in France].
AB  - Using data from a French national survey, preventive and dietary habits, alcohol
      and smoking consumption of three groups of migrants (Italy, Spain and Portugal,
      Maghreb) were compared to those of French nationals. Odds ratios were estimated
      using a logistic regression, after adjustment by age, socio-professional group
      and place of residence. Differences in attitude were observed, in particular:
      lower primary and secondary practice of prevention; lower consumption of meat and
      dairy products and higher consumption of starchy food and dried vegetables; lower
      consumption of alcohol and higher tobacco intake among Maghrebian migrants. The
      observed differences were interpreted in the light of other available data in
      France. They confirm notably imported dietary habits and a weaker perception of
      preventive messages, as shown in other studies.

PMID- 8552854
TI  - [Death due to drug addiction in Ile-de-France].
AB  - The aim of a cooperative study, carried out by the Paris Forensic Medicine
      Institute and the French National Institute of Health and Medical Research
      (INSERM SC8) was to assess the number of drug addiction-related deaths occurring
      in the Paris region in 1990. There were 253 deaths including 92 in Paris and 161
      in Paris suburbs. A large percentage of these deaths were not recorded in the
      National death statistics registry (only 36% of all the deaths and only 24% of
      the Paris deaths had been registered). The overall drug addiction mortality in
      the Paris region is 29.4 per million inhabitants and is highest among the 25-29
      year age group. Rates decrease rapidly after 30 years of age and are extremely
      low after 40. Mortality is highest in unmarried men and in the inactive
      population with a wide variability according to site of residence. Rates are much
      higher in Paris than in the suburbs. For the 20-29 year population in Paris, drug
      addiction has an important impact on the mortality figures for the general
      population, causing 12% of all deaths. It is the third cause of death after AIDS
      and suicide.

PMID- 8552855
TI  - [QALYS or not QALYS: that is the question?].
AB  - The article discusses the proposal of some health economists to use the "cost per
      QALY (quality-adjusted-life year)" ratio as an universal indicator for economic
      assessment of medical interventions, in the so-called "cost-utility" analyses.
      Authors argue that QALYs are not a straightforward application of expected
      utility theory, which is the standard economic model of individual behaviours
      toward risk and uncertainty. Indeed, QALYs are compatible with economic utility
      theory only if individuals' preferences regarding health states satisfy certain
      very restrictive properties: utility independence between length of life and
      quality of life, constancy of the proportional trade-off between quality of life
      and length of life, risk neutrality towards health states, constancy through time
      of the utility associated with each health state. Aggregation of individual QALYs
      to obtain an indicator for patient groups at the societal level also raises
      complex equity problems. Last but not least, from the epistemological point of
      view, QALYs are based on the hypothesis that health interventions only affect the
      health of the individual and not any other aspects of his well-being. The authors
      conclude that the "cost per QALY" approach should be abandoned in order to avoid
      ambiguities that could impede the development of health economics in the medical
      field.

PMID- 8552856
TI  - [Uncertainty, expertise and decision making: the lessons from the Montchanin
      landfill].
AB  - Three epidemiological studies were conducted at the urgent request of the
      administrative authority of the French department of Saone-et-Loire, in order to
      assess the health impact of volatile emissions from an industrial wastes dump
      situated in the vicinity of dwellings in the city of Montchanin, France (6,000
      inhabitants). These studies were implemented in the context of deep concern
      within the local population. Two dealt with the diagnosed morbidity before
      (retrospective follow-up study), or after (case-control study) the closure of the
      site. The third one dealt with mortality, for several causes of death liable to
      be related to the gazes emitted by the landfill (SMR analysis). Due to the small
      size of the population, these studies had limited statistical power. Despite
      these uncertainties, the authors claim that the decision to close the site was
      based on sound health considerations and recommend that the site be cleaned up.
      This experience illustrates the usefulness and the limitations of field
      epidemiological evaluations of environmental nuisances.

PMID- 8552857
TI  - [POLAIR: software and methodological guide for the epidemiological investigation
      of a point source atmospheric pollution].
AB  - The POLAIR software is designed to guide the user along a methodological approach
      to assess the health consequences of an accidental or chronic point source
      atmospheric pollution. This article presents the two components of the software,
      i.e. the gaussian modelization of the pollution contour lines on the territory
      around the emission source that allows to calculate an exposure index for every
      individual with a space-time ponderation factor, and the implementation, by using
      the EPI-INFO software, of a case-control or historical cohort epidemiological
      study among the population living in the vicinity of the source. Standardized
      questionnaires for the collection of data in the field are proposed, and the
      steps of the data analysis are commented upon, on the basis of an illustrative
      example.

PMID- 8552858
TI  - What's in a name? Names, definitions, descriptions, and diagnostic criteria of
      diseases, with emphasis on chronic obstructive pulmonary disease.

PMID- 8552859
TI  - Interpretation of extravascular thermal volume of the lung in patients with
      chronic pulmonary diseases.
AB  - To understand the significance of measured extravascular thermal volume of the
      lung (ETVL) in chronic pulmonary diseases, we measured ETVL using the double
      indicator dilution technique in 17 emphysematous patients and 15 patients with
      pulmonary fibrosis. The level of ETVL in emphysema is significantly correlated
      with parameters reflecting the severity of the disease, including FEV1.0% (r =
      0.54, p < 0.05), DLCO/VA (r = 0.54, p < 0.05), PaO2 (r = 0.61, p < 0.01), and
      mean pulmonary artery pressure (r = -0.61, p < 0.01). In pulmonary fibrosis, a
      significant inverse correlation was found between ETVL and PaO2 (r = -0.64, p <
      0.02), DLCO/VA (r = -0.58, p < 0.05), and %VC (r = -0.61, p < 0.02). The mean
      level of ETVL in both groups of patients was lower than previously reported
      normal values. These results suggest that ETVL may reflect the decrease in
      pulmonary vasculature in emphysematous patients, while it may signify a decrease
      of pulmonary vasculature and increased volume of pulmonary interstitial tissue
      surrounding the pulmonary vasculature in pulmonary fibrosis. We conclude that
      ETVL may represent a good estimate of the condition of the pulmonary vasculature
      and interstitial tissue volume in patients with chronic pulmonary diseases.

PMID- 8552860
TI  - Effect of low-dose endotoxin on pulmonary vascular permeability following acute
      hemorrhagic shock.
AB  - The purpose of the current study was to determine the effect of low-dose
      Escherichia coli lipopolysaccharide (LPS) on pulmonary vascular permeability when
      administered after hemorrhagic shock (40% of baseline cardiac output) followed by
      resuscitation. Animals were monitored for 3-4 h after LPS infusion. Thirty
      minutes prior to termination of the experiment, 3 mCi of 125I-human serum albumin
      was injected intravenously to calculate a permeability index from the left lung
      lavage and plasma 125I ratios. The two control groups were (1) shock only (no
      LPS, n = 4), and (2) LPS only (no shock, n = 8). The permeability index for the
      shock-only group was 0.0015 +/- 0.0007 (mean +/- SE) and that for the LPS-only
      group was 0.0035 +/- 0.0014. The permeability index for the experimental group
      (shock followed by LPS, n = 10) was 0.0071 +/- 0.0030 (p > 0.05). Similarly,
      there was no difference in the wet-to-dry ratios between the three groups. The
      shock+LPS group required more intravenous fluids to maintain mean arterial blood
      pressure at control values than the LPS-only group (p < 0.003). We conclude that
      hemorrhagic shock and resuscitation do not lead to an acute increased
      permeability of the lung when it is subsequently challenged by a low dose of
      bacterial LPS.

PMID- 8552862
TI  - Increased carcinoembryonic antigen concentrations in sera and bronchoalveolar
      lavage fluids of patients with pulmonary alveolar proteinosis.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare disease in which alveoli are
      filled with lipoproteinaceous materials. We measured carcinoembryonic antigen
      (CEA) concentrations in bronchoalveolar lavage (BAL) fluids and sera from
      patients with PAP and from healthy volunteers (HV). Significantly increased CEA
      values were found in BAL fluids and sera from patients with PAP compared with
      those from HV. BAL fluid CEA values significantly correlated to serum CEA values
      in patients with PAP. Serum CEA values significantly correlated to serum lactate
      dehydrogenase activity and alveolar-arterial PO2 difference values in patients
      with PAP. Successive measurements of serum CEA showed that serum CEA values
      reflect the disease activity of PAP. The determination of serum CEA is useful for
      evaluating disease severity of PAP.

PMID- 8552861
TI  - Quantification of fibronectin in bronchoalveolar lavage fluid and in lung
      parenchyma: differences between smokers and non-smokers.
AB  - Fibronectin (FN) is a glycoprotein present in the epithelial surface of airways
      and in the interstitial parenchyma of the lung. The aim of this study was to
      quantify the amount of FN in human lung parenchyma, and to investigate possible
      differences between smokers and non-smokers, both in lung parenchyma and in
      bronchoalveolar lavage (BAL) fluid. BAL fluid was recovered in 21 individuals.
      Quantification of FN in BAL was done by a non-competitive ELISA. Twenty-six lung
      parenchyma samples were also obtained from lung resections. FN was extracted with
      urea and heparin. Quantification of FN in lung parenchyma was determined by a
      competitive ELISA. The mean +/- SD FN content in BAL fluid from smokers was 1.59
      +/- 1.65 micrograms/mg total protein and 0.53 +/- 0.26 in non-smokers (p < 0.05).
      However, the amount of FN/ml BAL fluid was not statistically different between
      smokers (0.15 +/- 0.13 micrograms/ml) and non-smokers (0.106 +/- 0.07). The mean
      extractable FN in human lung tissue was 38.6 micrograms/g wet weight (31.7-45.5,
      95% mean confidence interval) with no statistical difference between smokers and
      non-smokers. We conclude that in smokers, FN accounts for a higher proportion of
      the total protein in BAL fluid, and that there were no differences in FN content
      in lung parenchyma between smokers and non-smokers.

PMID- 8552863
TI  - Methacholine-induced histamine liberation during airway challenge tests in
      Ascaris skin-sensitive sheep.
AB  - The interaction of vagal neuronal and pharmacological mediator mechanisms on the
      airway-constrictory responses obtained from challenges with aerosolized
      methacholine (MCH) before and after bilateral vagotomy and in combination with
      electrical stimulation of the peripheral ends of the cut vagal nerves was
      investigated in anesthetized Ascaris allergen skin-sensitive sheep. Inhalation of
      aerosols of 2 and 5% MCH for 2 min in a control group of 10 sheep resulted in
      airway muscle constriction indicated by an increase in dynamic elastance (Edyn)
      (+70 and +256% of the basic value) or inspiratory airway resistance (RI) (+45 and
      +155%) and was associated with a significant rise in plasma histamine
      concentration (HiPl) from 0.2 +/- 0.2 to 0.9 +/- 1.1 and 1.5 +/- 1.2 ng/ml,
      respectively. Respiratory and cardiovascular responses to MCH were reproducible
      after 90 min of recovery. A second group of another 6 intact sheep showed similar
      alterations of respiratory mechanical parameters and HiPl after MCH challenges.
      After bilateral vagotomy, Edyn and RI increased after 2 and 5% MCH inhalation
      only by 15-30% of the control responses with intact vagi. The diminished airway
      constriction was associated with similar changes in HiP1 as observed with intact
      vagi. Inspite of severe cardiovascular responses, the most effective electrical
      stimulation of the peripheral ends of the vagal nerves resulted in an increase in
      Edyn or RI by only 40-50% of the basic value. In a tracheal segment beneath the
      cuff of the endotracheal tube isometric pressure effectively increased by almost
      500% of the basic value. Vagus nerve stimulation was found without detectable
      changes in HiPl. Stimulation of the central ends of the vagal nerves did not
      induce airway constriction or alterations in HiPl. The combination of electrical
      vagus nerve stimulation and MCH inhalation resulted in a more than additive
      increase in Edyn and RI, but the airway responses did not reach the same level of
      obstruction after challenge with 5% MCH as observed with intact vagi. Electrical
      stimulation of the efferent vagi failed to stimulate spontaneous vagal nerve
      activity at higher levels of airway muscle responses. The results demonstrate
      that vagal neuronal mechanisms interact with local mediator liberation in acute
      airway obstruction. Airway challenge tests using cholinergic substances liberate
      histamine from inflammatory cells in the lungs of Ascaris skin-sensitive sheep.

PMID- 8552864
TI  - Prevalence of pneumonia due to Legionella pneumophila and Mycoplasma pneumoniae
      in a population admitted to a department of internal medicine.
AB  - We studied 177 patients with pneumonia admitted to an internal medicine
      department over a period of 3 years to determine the incidence of two emerging
      pathogens, Legionella pneumophila and Mycoplasma pneumoniae. Clinical,
      radiological and laboratory tests were performed and included blood cultures,
      serology, gram staining and sputum cultures. L. pneumophila was the agent
      involved in 9 patients (5.1%) and M. pneumoniae in 12 (6.8%). These prevalences
      were about in the middle of the range of previously published figures. Legionella
      pneumonia is a rare illness, which even in the absence of suggestive clinical
      signs must be considered because of its possibly serious course and to allow
      appropriate therapeutic decisions to be made.

PMID- 8552865
TI  - Incidence of tuberculosis in Greek armed forces from 1965-1993.
AB  - Studies investigating the epidemiology of tuberculosis in Greece are lacking.
      Tuberculosis (TB) continues to be a public health problem and its dimensions are
      not clearly defined. The aim of this study was to estimate the incidence of
      pulmonary and pleural TB in each of the three branches of military personnel
      serving in the Greek armed forces, during the period 1965-1993. All military
      personnel with confirmed pulmonary or pleural TB during the period 1965-1993 were
      studied retrospectively. The age of the patients ranged from 18-45 years. A
      significant number of TB patients were detected by the regular chest radiography
      screening using mass miniature radiography during enrollment. The diagnosis of TB
      was made both by clinical and paraclinical examinations, such as history,
      symptoms, physical examination, tuberculin skin reactivity, chest X-ray and/or
      computed tomography of the thorax, bronchoscopy, microbiological examination of
      specimens (sputum, washings, bronchoalveolar lavage) as well as histological and
      bacteriological examination of the biopsies. We found that during the period
      studied, 4,628 patients were hospitalised for TB, 3,588 for pulmonary TB, and
      1,040 for TB pleuritis (3,781 in the army, 445 in the navy and 402 in the air
      force). In 1965, the incidence (per 100,000) of TB (pulmonary and pleural) in the
      army was 60, in the navy 50, and in the air force 30. This incidence increased
      gradually from 1965 to 1980, followed by a decrease, since BCG vaccination became
      obligatory in 1980; values in 1993 were 18 in the army, 25 in the navy, and 15 in
      the air force. These figures are significantly higher than those reported for the
      civilian population, probably due to underreporting in the latter. Our results
      suggest that the incidence of TB in the Greek armed forces, although still high,
      is declining steadily. Strengthening of the anti-TB campaign is indicated.

PMID- 8552866
TI  - Pulmonary aspergillosis: early diagnosis improves survival.
AB  - Bronchoscopy obtaining bronchoalveolar lavage (BAL) fluid and bronchial
      secretions (BS) and/or high-resolution computed tomography (CT) of the lungs were
      performed in 33 patients with pulmonary aspergillosis from 1987 to 1992. The
      sensitivity of BAL fluid or BS for detecting histologically proven fungal disease
      was 33 and 50%, respectively, whereas positive serologies were only documented in
      8% of the cases. CT scans contributed to the early diagnosis of opportunistic
      fungal pneumonia: characteristic CT signs were found in 16 of 19 episodes. The
      more frequent use of bronchoscopy and CT scans between 1990 and 1992 compared to
      1987-1989 for the differential diagnosis of new pulmonary infiltrates resulted in
      earlier appropriate treatment. The average introduction of intravenous (i.v.)
      antifungal therapy after the onset of pneumonia was shifted from 12 to 7 days (p
      < 0.05). The timely implementation of i.v. antimycotic therapy had a significant
      impact on survival. Initiation of antifungal treatment later than 10 days after
      the onset of pneumonia resulted in a mortality of 90%, as opposed to 41% with an
      earlier start of antimycotics (p < 0.01). The earlier use of appropriate
      antifungal therapy in the second treatment period improved survival from 33 to
      50% (NS). Bronchoscopy and high-resolution CT scans are mutually complementary
      diagnostic tools and should be performed as early as possible in the course of
      pneumonia for patients at high risk for aspergillosis.

PMID- 8552867
TI  - Monitoring of nocturnal oxygen desaturation using pulse oximeter and apnomonitor
      in patients with chronic pulmonary disease.
AB  - The relationship between the degree of nocturnal oxygen desaturation (NOD) and
      pulmonary hemodynamics, pulmonary function tests, and resting awake blood gases
      was evaluated in patients with chronic pulmonary diseases (CPD). The severity of
      NOD correlated with the degree of impairment of pulmonary hemodynamics, but not
      with pulmonary function tests or resting awake blood gases. NOD was markedly
      alleviated by oxygen inhalation in CPD patients who did not develop sleep apnea.

PMID- 8552868
TI  - Adult onset of nemaline myopathy presenting as respiratory insufficiency.
AB  - A 49-year-old woman was admitted to the hospital for hypercapnia. Pulmonary
      function testing showed small lung volumes without parenchymal lung disease.
      Muscle enzyme levels were normal and the EMG was nonspecific. Finally, muscle
      biopsy revealed abundant nemaline bodies characteristic of nemaline myopathy.
      Nasal intermittent pressure ventilation was started with a preset pressure
      ventilator during sleeping hours with a good response.

PMID- 8552869
TI  - Obstructive sleep hypopnea syndrome in a patient with Marfan syndrome treated
      with oxygen therapy.
AB  - A patient with Marfan's syndrome and obstructive sleep hypopnea syndrome is
      reported. She had complained about insomnia, tiredness and hypersomnolence
      lasting 2 years. A complete nightly polysomnography revealed 94 obstructive
      hypopneas (the hypopnea index was 12.85) and no obstructive apneas. Presumably an
      increased laxity of the pharyngeal wall was responsible for the phenomenon. A
      therapy with CPAP was started, but was not tolerated by the patient. Oxygen
      therapy on the other hand turned out to be effective and well tolerated.

PMID- 8552870
TI  - DNA analysis of bronchoalveolar lavage in the diagnosis of pulmonary lymphoma.
AB  - Lung lymphomas frequently present a diagnostic challenge. The diagnosis of
      malignant lymphoma is possible when lymphocyte subpopulations show aneuploidy or
      a definable monoclonal surface marker or both. We present a case of lymphoma of
      the lung in which DNA analysis of bronchoalveolar lavage fluid was the first
      successful method in the time course of diagnosis.

PMID- 8552871
TI  - Serotypes of Pasteurella multocida and Pasteurella haemolytica isolated from
      pneumonic lesions in cattle and sheep from Mexico.
AB  - A total of 13,000 pairs of lungs were examined at Mexico's City abbatoir, where
      8,000 corresponded to sheep and 5,000 to cattle. From those, 224 pneumonic
      lesions were observed, obtaining 97 positive isolates, which yielded 112 strains
      of Pasteurella sp. Forty isolates were identified as P. haemolytica and 72 as P.
      multocida. One-hundred percent of P. haemolytica belonged to biotype A. Serotypes
      were determined by indirect haemagglutination. P. multocida isolates were
      classified according to the acriflavine and hyaluronidase techniques, 61%
      belonged to type A, 25% to type D and 14% were untypified. Somatic serotypes were
      determined by gel immunodiffusion; serotype 3 was more frequent, in sheep 72% and
      in cattle 77%.

PMID- 8552872
TI  - [Recovery of Staphylococcus aureus after acid damage].
AB  - The growth behavior of S. aureus in fresh cheese (Minas and Mozzarella) during
      their shelf life was studied in this research. The possibility of injury to this
      microorganism caused by increasing acidity was also investigated. Raw milk was
      inoculated with S. aureus FRIA-100 with approximately 10(6) cells/ml and cheese
      production was carried out according to normal procedures. They were stored at 7
      degrees C during 40 days for Minas cheese and during 60 days for Mozzarella
      cheese. At 2 to 3 days intervals the following analyses were performed: acidity,
      pH, S. aureus count on Baird-Parker agar by traditional methods and by the method
      recommended by the American Public Health Association, to count repair of injured
      cells. We were certain of the presence of injured S. aureus when acidity was in
      the range of 0.7 to 0.8% expressed as lactic acid and when the count was 1.3 log
      higher.

PMID- 8552873
TI  - [Hematologic changes associated with infection of mice by Cryptococcus
      neoformans].
AB  - The pathogenicity of the L, P and E strains of C. neoformans was studied in 3-5
      weeks old CD1 male mice. Cell suspensions containing the most (L), and the least
      (E) pathogenic strains were inoculated intracerebrally (IC), and
      intraperitoneally (IP). After 14 days total and differential counts were made for
      erythrocytes, leukocytes and platelets, yeasts from infected organs were
      recovered in Sabouraud Dextrose Agar (SDA). The capsular material from C.
      neoformans was used to stimulate in vivo and in vitro platelet production. Mice
      inoculated with the L strain, showed increase of neutrophils and platelets,
      decrease of lymphocytes, the yeast was recovered from spleen, liver and lungs and
      from brain of mice injected by the IC route. In contrast, strain E produced an
      increase of neutrophils, reduction of lymphocytes, and was only isolated from the
      brain of mice inoculated IC. The capsular material stimulated the production and
      maturation of megakaryocytes only in vitro. The development of the infection and
      the yeast dissemination were associated with increases in the number of
      platelets, probably as a result of the stimulant effect of the capsular material
      on the maturation of megakaryocytes.

PMID- 8552874
TI  - [Induction of polyvalent immunity against Actinobacillus pleuropneumoniae in an
      experimental rat model].
AB  - Using an experimental model of passive immunity in the rat, the immunizing effect
      of live cells of Actinobacillus pleuropneumoniae serotypes 1, 3, 5, 7, 9 and 12
      was tested against a challenge with serotype 1. It was observed that serotypes 5,
      7 and 9 induced polyvalent immunity. Additionally, agglutinating antibodies to
      the homologous and heterologous serotype were titrated in the sera of immunized
      mothers; the results indicated that groups immunized with serotypes 5, 7 and 9
      had higher titers against serotype 1.

PMID- 8552875
TI  - Induction of humoral immune response to Salmonella typhimurium in mouse Peyer's
      patches.
AB  - The mechanisms of immune response generation and regulation at the intestinal
      level are not well known, mainly due to the lack of suitable and reproducible
      methods to measure local immune responses. The Cunningham direct and indirect
      hemolytic plaque assay for the quantification of antibody producing cells against
      Salmonella in Peyer's patches of mice orally infected with Salmonella typhimurium
      was used. After infection IgM and IgG producing cells were determined on days 6,
      9, 12 and 19. Specific antibody producing cells appeared after bacterial invasion
      of Peyer's patches, nine days after infection. At this time, there were more
      antibody producing cells in the distal part of the intestine, which correlated
      with a higher infection of these Peyer's patches as detected by bacterial
      culture. After day nine, the number of plaque forming cells was similar in both
      parts of the intestine. The peak of response was on day 12 and diminished on day
      19. The number of IgM and IgG producing cells was similar in all days analyzed.
      Histological analysis of Peyer's patches of infected mice showed inflammation
      with disorganization and tumefaction.

PMID- 8552876
TI  - Antibody response to Mycobacterium tuberculosis antigens in children with
      pulmonary tuberculosis and in BCG vaccinated non tuberculous pediatric patients.
AB  - In this work we look for the antibody response to M. tuberculosis antigens in 38
      children with pulmonary tuberculosis: 18 bacteriologically and 20 clinically
      diagnosed as compared to the response of 52 children with other respiratory
      illnesses in which tuberculosis was definitively ruled out. In this control group
      24 had been BCG vaccinated and 28 had not. Antibodies were detected by ELISA and
      immunoblot using a crude extract of M. tuberculosis as antigen. All 38
      tuberculous diagnosed children tested positive, by ELISA, to the bacterial
      extract as did previously vaccinated controls (18/24), while all 28 non
      vaccinated controls gave negative results (sensitivity = 1.0, specificity =
      0.68). By Western blot, tuberculous patients recognized a 12 kDa protein that was
      not recognized by the control vaccinated group. This partially purified protein
      which was used in an ELISA resulted positive in all 18 bacteriologically, in
      17/20 clinically diagnosed patients, and in only 6/24 vaccinated controls.
      Specificity increased to 0.86, with a sensitivity of 0.93.

PMID- 8552877
TI  - [Fasciolinip-1: experimental fasciolicidal activity in sheep].
AB  - The aim of the present study was to evaluate the flukicide efficacy of the 2
      amino-5(6)-chloro-1-methoxycarbonylbenzimidazole (II), named Fasciolinip-1,
      against eight and twelve-week old flukes in sheep. In a first experiment 35 young
      sheep were infected each with 300 metacercariae of Fasciola hepatica. Eight weeks
      postinfection five groups of seven animals each were treated as follows: Groups
      1, 2 and 3 were given 2.5, 5 and 10 mg/kg of Fasciolinip-1. Groups 4 and 5
      remained as non-treated and vehicle controls, respectively. In a second study, 32
      sheep were infected each with 150 metacercariae. Twelve weeks postinfection, the
      animals were divided into 4 groups of 8 sheep each. Groups 1, 2 and 3 were
      treated orally with 5, 10 and 15 mg/kg of Fasciolinip-1, respectively. Group 4
      remained as non-treated control. Fifteen days after treatment, all sheep from
      both experiments were killed to collect the flukes present in liver. Results
      indicated efficacies of 19.1%, 49.6% and 65.2% for groups 1, 2 and 3 of the first
      study and 48.3%, 64.8 and 90.6% for sheep of the second experiment, respectively.
      It was concluded that Fasciolinip-1 removed 8-week old flukes in limited numbers
      and 12-week old flukes in 90.6% when used at 15 mg/kg body weight.

PMID- 8552878
TI  - [Evaluation of chemotherapeutic agents against cichlidogyriasis in tilapia
      (Oreochromis hornorum) in Mexico].
AB  - To evaluate the efficacy of seven compounds against the cichlidogyriasis of
      tilapia fish (Oreochromis hornorum), two experiments were carried out. In one,
      160 naturally infected fish with a mean burden of 33.4 parasites/animal were
      used. In another, 1600 fish with a burden of 49.9 parasites/fish were used. Fish
      were randomly divided into eight equal groups and received three treatments as
      submersion baths: methylene blue, malachite green, potassium permanganate, sodium
      chloride, formaldehyde, copper sulfate and triclorfon, and a non-treated control.
      Five days after the last treatment, all fish were killed and dissected to
      quantify the remaining parasites. All data were submitted to an ANOVA analysis.
      All groups compared to the control showed statistical difference (P < 0.01), with
      better efficacy at higher doses. Sodium chloride, potassium permanganate and
      triclorfon are highly efficient in the control of cichlidogyriasis of tilapia
      fish, but care should be taken with the toxicity of the two first compounds.

PMID- 8552879
TI  - [Frequency of isolation of Ureaplasma urealyticum in an open population from
      southern Mexico City].
AB  - Vaginal cultures for Ureaplasma urealyticum and confidential questionnaires were
      obtained from women with signs and symptoms of vaginitis who consulted a
      physician at a Primary Health Center, Tlalpan, D.F., Mexico. In all 220 women
      were studied, 50 (22.7%) of whom were colonized with Ureaplasma urealyticum,
      statistical analysis (X2) showed there was no association between colonization
      with Ureaplasma urealyticum, and age, pregnancy, and other but there was
      association between colonization with Ureaplasma urealyticum and the number of
      pregnancies and no birth control method use.

PMID- 8552880
TI  - [Leptospirosis in animal reproduction: III. Role of the hardjo serovar in bovine
      leptospirosis in Rio de Janeiro, Brazil].
AB  - Four hundred and five serum samples were drawn from cows with reproductive
      problems which were not vaccinated against leptospirosis from 21 dairy farms.
      Three distinct geographic regions were determined and the farms were also
      classified considering the production system, based on technological,
      zootechnical and sanitary resources. A total of 277 positive reactions were
      observed, corresponding to 68.39% of the samples. The predominant serovar was
      hardjo, reactive on 85 samples (20.98%), predominant on nine farms and observed
      on 17 farms (80.95%). It was observed the predominance of hardjo in all studied
      regions and on properties classified as type "A" (22 samples) and type "B" (49
      samples). The role of this serovar on bovine leptospirosis in Brazil compared
      with other countries is discussed.

PMID- 8552881
TI  - [Effect of carbaryl and lead on phenols, chlorophyll and proteins of the
      microalga Ankistrodesmus falcatus].
AB  - Considering that Ankistrodesmus falcatus is very sensitive to different
      pollutants, in this work the effect of lead, carbaryl and a mixture of both
      pollutants on protein, chlorophyll and phenols concentration in this microalga
      have been studied. At different lots of Ankistrodesmus falcatus in the middle of
      the log growth phase, different concentrations of lead, carbaryl and a mixture of
      both pollutants were added, during 24, 48 and 72 h. Chlorophyll, proteins and
      phenols concentration was measured. The results show that the mixture of lead
      carbaryl produces a major toxic effect than the xenobiotics by themselves, so it
      has been suggested that to establish permissible limits it is necessary to
      consider the synergism presented in simultaneous exposure to both xenobiotics. It
      is suggested to use phenols determination as a primary indicator of environmental
      impact in an aquatic ecosystem.

PMID- 8552882
TI  - Effects of night work on the cognitive function in young and elderly subjects
      with specific reference to the auditory P300.
AB  - To estimate the effects of night work on the human cognitive function, P300 event
      related potentials (ERPs) evoked with an auditory "oddball" paradigm were
      recorded for 17 nurses (mean age 27.4 +/- 6.1 years; range 21-41 years) for 3
      epochs; after a night of work, after a day of work and on a holiday, and for 12
      elderly security guards (mean age 62.8 +/- 2.2 years; range 60-67 years) for 2
      epochs; after a night of work and on a holiday. The Stress Arousal Check List
      (SACL) was used for all the subjects just prior to the P300 ERP recording to
      determine the extent of stress and the arousal grades. Fourteen of the nurses
      were in their twenties (mean age 24.9 +/- 2.6 years; range 21-29 years), and 3
      (39.0 +/- 2.6) were older (36, 40 and 41 years). The 14 nurses were classed as
      the young group. All the security guards were classed as the elderly group. In
      the young group, the stress grade scores increased significantly (P < 0.05) and
      the arousal grades decreased significantly (P < 0.01) after night work as
      compared to the holiday values. Although statistically not significant, the
      amplitude of the P300 component tended to decrease after night work, whereas the
      latency was very stable for these 2 epochs. The P300 latencies of the 3 older
      nurses were as stable as those of the young group, but their amplitudes were
      significantly reduced after night work as compared with the holiday amplitudes (P
      < 0.05). In contrast, the 12 elderly security guards showed no statistically
      significant changes in the scores for the stress and arousal grades between the 2
      epochs, after night work and holiday. Latency prolongation however, was
      statistically significant (P < 0.01) after night work. The P300 amplitudes for
      many of the elderly security guards also tended to decrease after night work, but
      were not statistically significant. The P300 amplitude is considered to reflect
      the amount of attentional resources and the latency to reflect the time needed
      for the cognitive process, indicating that the elderly security guards
      experiences slowing of the cognitive process in night work. Our results suggest
      that the effect of night work on the cognitive function is greater for elderly
      than for young workers. We conclude that P300 can be used to evaluate changes in
      the human cognitive function produced by night or rotating shift work and that
      the results provide useful information with which to plan shift schedules on the
      basis of worker age.

PMID- 8552883
TI  - [Measurement of airborne fumes in welding factories].
AB  - Concentrations and size distributions of airborne welding fumes in work
      environments were measured. Samples were collected from 20 workplaces in 13
      companies. In all workplaces, the stationary samplings including A-sampling and B
      sampling and the personal sampling were carried out simultaneously. The fume
      concentration in the stationary sampling was measured with a digital dust
      monitor. A low volume air sampler and an Anderson cascade impactor was also used
      to determine the conversion factor of the values obtained by the digital dust
      monitor and the size distributions of the fumes. The personal exposure levels
      were measured with a TR sampler and a personal cascade impactor. The
      concentrations by the personal sampling (average: 11.3mg/m3) were much higher
      than those by the A-sampling (average: 0.4mg/m3 and range: 0.15-0.64mg/m3) but
      lower than those by the B-sampling (average: 46.8mg/m3, range: 0.66-152.8mg/m3).
      The mass median aerodynamic diameter (MMAD) of the stationary and the personal
      samplings were 2.41 microns and 0.80 microns, respectively. Fumes were observed
      under a scanning electron microscope. Most of the fume particles were sphere in
      shape but smaller fumes were aggregated and formed larger secondary particles.

PMID- 8552884
TI  - [Study of diffusion phenomenon using an experimental magnetic resonance system
      (SIS 200/400) for small animals--reliability and apparent diffusion coefficient
      of normal animals].
AB  - We have developed a magnetic resonance (MR) spin echo method to obtain diffusion
      weighted imaging using motion probing gradient (MPG) pulses in orthogonal
      direction before and after a 180 degree pulse. Phantom models containing water,
      acetone, cupric sulfate and agar, and normal brains of Wistar rats and puppies
      were examined. MRI was performed using a SISCO SIS 200/400 MRI/MRS experimental
      system for small animals (4.7 tesla, 400 mm bore). The apparent diffusion
      coefficient (ADC) values, given in mm2/sec, were 2.19 +/- 0.02 x 10(-3) in water,
      4.51 +/- 0.18 x 10(-3) in acetone, and the ADC of water was independent on
      longitudinal (T1) or transverse (T2) relaxation time. Time-dependent ADC changes
      were not demonstrated, however position-dependent ADC changes were significant.
      It is therefore important to set the sample at the same position for repeated MRI
      studies and for the evaluation of the time course of experimental studies. Mean
      ADC values of rat brains were 0.65 x 10(-3) for cortex, 0.69 x 10(-3) for caudate
      putamen, 0.69 x 10(-3) (perpendicular to axon) for corpus callosum, 1.11 x 10(-3)
      (parallel to axon) for optic nerve, and 1.38 x 10(-3) (parallel to axon) for
      trigeminal nerve. Those of puppies were 1.14-1.42 x 10(-3) for gray matter, 1.17
      (parallel to axon) and 0.89 (perpendicular to axon) x 10(-3) for white matter,
      1.66 (parallel to axon) and 0.57 (perpendicular to axon) x 10(-3) for internal
      capsule, and 0.91-0.95 x 10(-3) for thalamus. On the in vivo ADC maps, white
      matter tracts successfully showed anisotropic diffusion. This technique has
      promising implications for the evaluation of the time course of cerebral damage
      and degenerative changes.

PMID- 8552885
TI  - [Application of molecular biology to occupational health field--the frequency of
      gene polymorphism of cytochrome P450 1A1 and glutathione S-transferase M1 in
      patients with lung, oral and urothelial cancer].
AB  - A polymorphism in exon 7 of the cytochrome P450 1A1 (CYP1A1) and A homozygous
      gene deletion at the glutathione S-transferase M1 (GSTM1) locus of genomic DNA
      isolated from peripheral blood were investigated for its relationship with lung,
      oral and urothelial cancer using the polymerase chain reaction (PCR) technique.
      As for the CYP 1A1 Val/Val genotype, 5 of 88 healthy controls (5.6%), 1 of 33
      lung cancer patients (3.0%, P > 0.05, odds ratio 0.52, 95% confidence interval
      0.21-17.3 with Ile/Ile Ile/Val type as base line), 4 of 32 oral cancer patients
      (12.4% P > 0.05, odds ratio, 2.37, 95% confidence interval 0.60-9.30) and 4 of 85
      urothelial cancer patients (4.8% P > 0.05], odds ratio, 0.82, 95% confidence
      interval 0.21-3.16) were CYP 1A1 Val/Val types. The frequency of GSTM1 deletion
      genotype was 39.8% in the healthy controls and 45.5%, 50.0% and 61.2% in lung
      cancer, oral cancer and urothelial cancer patients, respectively. The frequency
      of GSTM deletion genotype was statistically increased in urothelial cancer
      patients (P < 0.05, odds ratio 2.38, 95% confidence interval 1.28-4.34). The odds
      ratio of combined genotypes of CYP1A1 Val/Val and GSTM1 deletion was 1.42 (95%
      confidence interval 0.12-16.8), 3.64 (95% confidence interval 0.47-27.9), 1.02
      (95% confidence interval 0.14-7.53) in lung cancer, oral cancer and urothelial
      cancer patients, respectively. Thus, the GSTM1 deletion genotype as a host factor
      predisposing to urothelial cancer was proved in this study.

PMID- 8552886
TI  - [An AHP analysis on factors associated with the career choice of medical students
      of UOEH].
AB  - In order to clarify factors associated with the career choice of medical students
      of UOEH, an AHP (Analytic Hierarchy Process) analysis was employed for 4th year
      medical students in 1994 (86 students). As factors associated with career choice,
      the following three factors were evaluated as important in the following order;
      'work worth engaging in', 'income', and 'identity as a medical doctor'. For these
      three major factors, the surgeon was evaluated as the most favorable, followed by
      the physician, the clinician of other sectors (ORL, ophthalmology, etc), the
      occupational physician, researcher, and medical doctors in the administration.
      When comparing students who wanted to be clinicians and those who wanted to be
      occupational physicians, the latter group attached more importance to 'stability'
      and 'scholarship'. Finally, the present AHP analyses clarified that students
      prefer to become clinicians regardless of their expressed preference for a future
      career. This fact has created for us an educational problem to be discussed in
      future curriculum meetings of UOEH.

PMID- 8552887
TI  - Practical methodology of meta-analyses (overviews) using updated individual
      patient data. Cochrane Working Group.
AB  - Meta-analyses using updated individual patient data may provide the most reliable
      means of combining data from similar randomized controlled trials. The benefits
      of this approach to systematic reviews are described. Guidance, based on the
      experience of several groups who have undertaken such projects, is given. This
      includes practical advice on initiating and maintaining collaboration, the time
      and resources required to undertake these usually international projects and
      methods of data checking and validation. Example proforma are included.

PMID- 8552888
TI  - The design and analysis of randomized trials with recurrent events.
AB  - This paper describes a method for planning the duration of a randomized parallel
      group study in which the response of interest is a potentially recurrent event.
      At the design stage we assume patients accrue at a constant rate, we model events
      via a homogeneous Poisson process, and we utilize an independent exponential
      censoring mechanism to reflect loss to follow-up. We derive the appropriate study
      duration to ensure satisfaction of power requirements for the effect size of
      interest under a Poisson regression model. An application to a kidney transplant
      study illustrates the potential savings of the Poisson-based design relative to a
      design based on the time to the first event. Revised design criteria are also
      derived to accommodate overdispersed Poisson count data. We examine the frequency
      properties of two non-parametric tests recently proposed by Lawless and Nadeau
      for trials based on the above design criteria. In simulation studies involving
      homogeneous and non-homogeneous Poisson processes they performed well with
      respect to their type I error rate and power. Results from supplementary
      simulation studies indicate that these tests are also robust to extra-Poisson
      variation and to clustering in the event times, making these tests attractive in
      their generality. We illustrate both tests by application to data from a
      completed kidney transplant study.

PMID- 8552889
TI  - An application of decision theory to patient screening for an autologous tumour
      vaccine trial.
AB  - Patients are eligible for accrual onto a phase I autologous tumour vaccine
      clinical trial if their resected and dissociated tumour achieves a minimum viable
      cell count. Because tumour pre-processing and cell count determination are
      expensive, there has been developed a screening procedure based on tumour mass to
      screen out those tumours unlikely to yield sufficient viable cells. If theta is
      the ratio of the expected benefit of an accrual onto the study to the cost of
      tumour pre-processing and cell counting, then we maximize long-run benefit by pre
      processing and counting only those tumours whose masses exceed a cutoff mc, such
      that Pr(sufficient tumour cells masses = mc) = 1/theta. We derive algorithms for
      estimating mc and evaluate them under a variety of assumptions concerning the
      cell count/mass relationship. These include explicit equations for mc under
      parametric assumptions as well as more general algorithms based on non-parametric
      smoothing techniques. We show that when theta deviates substantially from 2,
      these methods outperform simple inverse interpolation.

PMID- 8552890
TI  - Two-sample rank tests for acceleration in cure models.
AB  - I derive the locally most powerful rank tests for acceleration against semi
      parametric alternatives when some patients are cured of the disease. I consider
      some particular classes of alternatives and present simulation results to verify
      the validity of the proposed tests. Real data from clinical trials for childhood
      leukaemia illustrate the proposed tests.

PMID- 8552891
TI  - The restricted cubic spline as baseline hazard in the proportional hazards model
      with step function time-dependent covariables.
AB  - We incorporate a cubic spline function where the tails are linearly constrained,
      as the baseline hazard, into the proportional hazards model. We show estimation
      of covariable coefficients and survival probabilities with this model to be as
      efficient statistically as with the Cox proportional hazards model when
      covariables are fixed. Examples show that the inclusion of time-dependent
      covariables defined as step functions into the restricted cubic spline
      proportional hazards model reduces computation time by a factor of 213 over the
      Cox model. Advantages of the spline model also include flexibility of the hazard,
      smooth survival curves, and confidence limits for the survival and hazard
      estimates when there are time-dependent covariables present.

PMID- 8552892
TI  - Standardized estimates from categorical regression models.
AB  - We consider the problem of interpreting categorical regression models, such as
      the polytomous logistic model, the continuation-ratio model, the stereotype
      model, and the cumulative-odds model. We present a method to convert categorical
      regression coefficients into estimates of standardized fitted probabilities,
      probability differences and probability ratios. We use a delta-method approach to
      estimate standard errors. We then present a small simulation study to compare
      different transforms for setting confidence limits, and provide an illustration
      of our approach in an observational study of drug therapy of polymyositis.

PMID- 8552893
TI  - Exact logistic regression: theory and examples.
AB  - We provide an alternative to the maximum likelihood method for making inferences
      about the parameters of the logistic regression model. The method is based
      appropriate permutational distributions of sufficient statistics. It is useful
      for analysing small or unbalanced binary data with covariates. It also applies to
      small-sample clustered binary data. We illustrate the method by analysing several
      biomedical data sets.

PMID- 8552894
TI  - Confidence interval estimates of an index of quality performance based on
      logistic regression models.
AB  - This paper considers an index of hospital quality performance defined as the
      ratio of the observed number deaths to the number predicted by a fitted logistic
      regression model. We study tests and confidence intervals under two different
      scenarios depending on the availability of an estimate of the covariance matrix
      of the coefficients from the fitted logistic regression model. We propose
      parametric as well as bootstrap-based confidence intervals. We apply the methods
      to an analysis of the performance of 27 intensive care units.

PMID- 8552895
TI  - Prediction and decision making using Bayesian hierarchical models.
AB  - This paper uses Bayesian hierarchical models to analyse multi-centre clinical
      trial data where the outcome variable of interest is continuous, but not normally
      distributed, and where censoring has occurred. The goal of such an analysis is
      the same as for any subgroup analysis, to provide survival estimates for specific
      subgroups as well as for the population and to provide estimates of the degree of
      heterogeneity between subgroups. An analysis of the Collaborative Study of Long
      Term Maintenance Drug Therapy in Recurrent Affective Illness, a multi-centre
      clinical trial funded by the National Institute for Mental Health's Pharmacologic
      Research Branch, serves to illustrate the proposed methodology. A feature of this
      data set is that one treatment group was withdrawn from medication at the time of
      randomization. The paper contains comparison of models, one that accounts for the
      drug washout period through the use of a changepoint model as well as a
      comparison of results across several choices of prior parameter values. In
      addition, the paper considers sensitivity to model choice and priors in a
      decision theory context.

PMID- 8552896
TI  - Modelling mortality and morbidity of newborns.
AB  - Data of 10,514 singleton births collected over a ten year period at a single
      hospital are analysed and models linking birthweight and gestational age with
      mortality and morbidity defined by low Apgar scores are constructed and compared.
      Based on these models, charts of mortality and morbidity are drawn and compared
      with common charts of birthweight centiles. Classification rules for newborns at
      risk are defined by iso-mortality contours, marginal birthweight centiles, and
      birthweight centiles adjusted by gestational age, respectively, and compared
      using receiver operating characteristic (ROC) curves. The results suggest that,
      as far as neonatal mortality is concerned, classification rules based on simple
      marginal birthweight centiles perform almost as well as iso-mortality contours
      and considerably better than birthweight centiles adjusted for gestational age.

PMID- 8552897
TI  - Longitudinal models for analysis of respiratory function.
AB  - We compare the results of fitting three longitudinal models, two autoregressive
      models (the serial correlation model and a damped autoregressive model) and a
      compound symmetry model, to data on a cohort of 1154 adult men in Boston. The
      serial correlation model assumes that the error terms are autocorrelated with
      correlation of the form lambda t for visits t years apart while the damped
      autoregressive assumes that the correlation between error terms of observations t
      years apart is of the form lambda t theta. The compound symmetry model assumes
      that the errors are correlated, with the same correlation regardless of how far
      apart observations are in time. These three models are all related in that the
      serial correlation and compound symmetry models are particular cases of the
      damped autoregressive models (that is, theta = 1 corresponds to the serial
      correlation model and theta = 0 corresponds to the compound symmetry model). For
      current smokers, the damped autoregressive model provided a significantly better
      fit than either of the other two models (p < 0.001); for never smokers the damped
      autoregressive and compound symmetry models were almost identical with both
      providing a significantly better fit than the serial correlation model (p <
      0.001).

PMID- 8552898
TI  - A statistic for comparing two correlated markers which are prognostic for time to
      an event.
AB  - A proliferation of biologic markers has led to increased interest in methods for
      comparing the prognostic value of markers in predicting time to recurrence of or
      death from disease. This paper proposes a nonparametric test statistic for
      comparing two continuous markers when the outcome of interest is time to an event
      and the outcome is subject to right censoring. Results from Monte Carlo studies
      show that the new testing procedure is reliable for practical use. We present an
      example in which we use the statistic successfully in a colon cancer study to
      select between two potentially useful markers.

PMID- 8552899
TI  - A simulation study used to design the sequential monitoring plan for a clinical
      trial.
AB  - In designing a sequential monitoring plan for the AVID (Antiarrhythmics Versus
      Implantable Defibrillators) study, a multi-centred clinical trial, we completed a
      simulation study to help ourselves and the Data Safety Monitoring Board
      understand the implications of various monitoring plans. In particular, we
      compared three test statistics and three use functions. Simulation was based on
      approximate trial parameters and two plausible but distinct alternative
      hypotheses. The power to detect a difference between the two treatment arms was
      computed as a function of time. The simulated results illuminate several of the
      important statistical and ethical issues involved in selecting a sequential
      monitoring plan and illustrate how one can use simulations to design a clinical
      trial.

PMID- 8552900
TI  - Re-evaluating design specifications of longitudinal clinical trials without
      unblinding when the key response is rate of change.
AB  - The design of clinical trials often requires knowledge of quantities such as
      between- and within subject variances about which only imprecise information
      exists. To provide assurance that the study has the desired power to detect a
      minimum clinically meaningful difference between treatment groups. Gould, Gould
      and Shih, and Shih have recommended obtaining relevant information from the trial
      at an interim stage without unblinding. Wittes and Brittain provided a similar
      recommendation, but viewed the portion up to the interim stage as an (internal)
      pilot study and required unblinding. This paper considers the problem of re
      evaluating the design specifications in longitudinal clinical trials when the key
      response is the rate of change (slope). The proposed method aims to re-evaluate
      the sample size and study duration in a way that maintains the trial's blinding,
      using an EM algorithm. Simulation results show that the effect on type I error
      rate in negligible, but the potential gain in power can be substantial. The
      procedure is simple to use in practice, as it does not unblind patients'
      treatment identifications, and, since it does not unveil the relative efficacy of
      treatments, it fulfils the requirement of a valid 'administrative' (interim)
      analysis.

PMID- 8552901
TI  - Designing a cost-effective clinical trial.
AB  - Researchers and administrators must decide which clinical trials are worth doing
      and how many subjects are needed for a trial. We calculated sample size
      considering the costs of implementing the results of the trial and the trial
      costs using (1) Neyman-Pearson methods and (2) a Bayesian cost-benefit method. We
      illustrate these methods in a clinical trial sponsored by the National Institutes
      of Health that compares two levels of blood urea nitrogen clearance by
      haemodialysis for patients with end-stage renal disease. When applied to
      evaluations of research proposals, these methods may help researchers to decide
      whether to begin a study, and, if so, how many subjects to enrol in it. These
      methods should be especially useful for large studies intended to inform health
      policy.

PMID- 8552902
TI  - Exact power computation for dose-response studies.
AB  - The toxicity of an agent or the therapeutic effect of a drug may be assessed by a
      dose-response study. We present a method for computing the exact power of exact
      and large sample statistical tests employed for binary response data from such a
      study. This method, based on recursive polynomial multiplications, enables fast
      computation of exact power for studies with up to a moderately large sample size.
      We demonstrate the efficiency of our method using three examples. The method is
      suitable for the design and power analysis of dose-response studies in which the
      usual asymptotic approximations are suspect.

PMID- 8552903
TI  - Sample size determination for comparing more than two survival distributions.
AB  - We examine the asymptotic properties of the Tarone and Ware and Harrington and
      Fleming classes of test statistics under alternative hypotheses when there are
      comparisons between more than two survival distributions in the presence of
      arbitrary right censoring. When we assume equal censoring distributions across
      treatment groups and proportional hazards, we derive the sample size formula for
      testing the equality of k > or = 2 survival distributions using the logrank test.
      This work extends Schoenfeld's derivation for comparing two survival
      distributions and also generalizes the results of Makuch and Simon. We also
      derive the sample size formula for testing monotone dose-response using Tarone's
      trend test. We then investigate the practicality of the formula in various
      situations by presenting empirical power with use of Monte Carlo simulations. In
      addition, with stratification present, we derive the sample size formula for the
      stratified logrank test, which is an extension of Palta and Amini.

PMID- 8552904
TI  - In defence of analysis of covariance: a reply to Chambless and Roeback.

PMID- 8552905
TI  - Modelling covariate effects in observer agreement studies: the case of nominal
      scale agreement.

PMID- 8552906
TI  - [Chronic lumbago: health insurance stakes].

PMID- 8552907
TI  - [Disabling chronic lumbago: avoidable or unavoidable?].

PMID- 8552908
TI  - [Psychosocial aspects of chronic lumbago: the physicians and patients' behavior].

PMID- 8552909
TI  - [Disabling chronic lumbago: should one be concerned about the couple and the
      family?].

PMID- 8552910
TI  - [Economics and chronic lumbago. Role of the medical consultant].

PMID- 8552911
TI  - [Disabled insurance payments: when and how to have recourse to it?].

PMID- 8552912
TI  - [Impact of HMOs on costs and quality of care].

PMID- 8552913
TI  - [Apropos of the project to liberalize the abortion law in Spain].

PMID- 8552914
TI  - [Acalculous cholecystitis in Schoenlein-Henoch syndrome. Apropos of a case].
AB  - We describe the case of a 51 year-old man affected of relapsing bouts of
      abdominal pain and hematuria, who began acutely with pain in the right upper
      quadrant, fever, hematuria, arthralgias and purpura on the lower extremities;
      ultrasonography revealed the existence of acalculous cholecystitis. The lack of
      response to intravenous antibiotherapy and the clinical association of
      cholecystitis to the renal, cutaneous and articular manifestations, oriented to
      the diagnosis of Schoenlein-Henoch vasculitis; thereafter, the response to
      steroids was successful and immediate. The etiologic diagnosis of this case of
      acalculous cholecystitis based on clinical aspects, avoid the surgical therapy
      and the possible morbidity that this procedure can produce.

PMID- 8552915
TI  - [Normal values for basal serum gastrin with and without stimulation].
AB  - In the present work we report a study of the basal gastrin serum levels and
      stimulated serum gastrin levels after an hyperproteic meal, in a group of 20
      healthy volunteers, with neither actual nor previous digestive symptoms. 60% were
      males, with a mean age of 35, 7 years, the highest percentage (40%) belonging to
      the fourth decade of life. The procedure used to determine serum gastrin levels
      is described. The mean value of the 3 samples obtained in basal conditions was of
      51.01 pg/ml. The mean value of the 6 samples obtained after the stimulation meal
      was of 73.4 pg/ml. The results obtained in this study are discussed and compared
      with the ones of the reviewed literature.

PMID- 8552916
TI  - [Effects of exercise in the elderly with chronic renal failure].
AB  - The population studied in this paper is composed of 10 patients under
      hemodialysis, who have underwent a general exploration, a stress test, a
      spirometry, an analytic control and assessment of exercise their psychological
      situation, before and after the programme. At the end of the training programme
      there is an important increase in the SVC and the FVC, as well as the power and
      time of the stress test. The psychological state improves as well as the anaemia.

PMID- 8552917
TI  - [Stable isotopes in biomedical diagnosis and research].
AB  - Atoms that are chemically identical but that differed slightly in weight due to
      the number of nuclear neutrons are called isotopes stables, meaning that do not
      degrade spontaneously. Mass spectrometry is the analytical technique to evaluate
      the enrichment on these isotopes with a variety of applications in the clinical
      diagnosis of pathological processes and the quantitation of metabolic events such
      as bacterial growth (Helicobacter pylorii), Phenylketonuria, lactose intolerance,
      liver and pancreatic function, body composition and energy expenditure,
      cholesterogenesis, glucose utilization, etc. in an easy, non-invasive and
      specific way as mass spectrometers develop.

PMID- 8552918
TI  - [Update on familial Mediterranean fever].

PMID- 8552919
TI  - [Nabumetone].

PMID- 8552920
TI  - [How can we help children during the terminal phase?].
AB  - Children with terminal illness make a deep impression on everybody around them.
      They need help in communication, respect and a lot of affection. There are
      different ways to help them to overcome their problems. The family requires
      support in the different phases of adaptation to the illness and in the
      bereavement period. We emphasize the role of the carer.

PMID- 8552921
TI  - Sleep rhythmicity in premature infants: implications for development status.
AB  - Ultradian and diurnal rhythms in premature infants were investigated by assessing
      cyclicity of quiet sleep (QS) and the diurnal distribution of this cyclicity. The
      sleep of 49 preterm infants was recorded in the hospital for three successive 24
      hour periods at 36 weeks conceptional age (CA), and 42 of the infants were
      recorded in the home for two 24-hour periods when they were 6 months old. Sleep
      was recorded nonintrusively by means of the motility monitoring system, which
      does not require instrumentation of the subject. Cyclicity was assessed using a
      procedure that permits assessment of significance as well as degree of cyclicity.
      Twenty of the 49 infants at the preterm age and 37 of the 42 infants at 6 months
      had sleep episodes with significant cyclicity. Mean cyclicity scores increased
      from 0.61 to 0.81 over age, but the cycle length of approximately 60 minutes did
      not change. There was no evidence for individual consistency across the two ages
      in any of the sleep or cyclicity measures. Evidence for diurnal differences was
      present from the preterm period. At both ages, there were far more analyzable
      sleep episodes and higher cyclicity at night. At the preterm period, cyclicity
      measures were negatively related to indices of advanced perinatal status as well
      as 6-month mental scores; at 6 months, the cyclicity measures were positively
      related to perinatal measures as well as mental scores. These results indicate
      the necessity for different interpretations of periodicity at the preterm and
      later age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8552922
TI  - Postnatal adaptation of brain function in full-term neonates as assessed by EEG
      sleep analyses.
AB  - Differences in electroencephalographic (EEG) sleep between preterm and full-term
      neonatal cohorts at matched postconceptional ages have been previously presented
      by our study group. These differences may have occurred, however, because of
      postnatal brain adaptation of the full-term infant after a more recent delivery.
      EEG sleep analyses, therefore, were performed on only the full-term cohort to
      determine if EEG sleep measures changed over the first three days after birth,
      which might account for the differences with the preterm group. Twelve full-term
      infants studied on the first day of life were compared with 17 full-term infants
      who were studied on days of life 2 and 3. Using multivariate analysis of variance
      (MANOVA), comparisons were performed among 13 EEG sleep measures. No EEG sleep
      differences were seen between full-term children born by Cesarean section versus
      those born by vaginal presentation. No statistical differences were noted between
      day 1 compared to days 2 and 3 with respect to 10 measures concerning sleep
      architecture, phasic, continuity, spectral EEG, and autonomic features. In three
      EEG sleep measures, changes occurred between days 1 and 2-3, but two of the three
      measures were in a direction that strengthen our claim that differences exist
      between preterm and full-term cohorts: more body movements and lower percentages
      of quiet sleep were noted for full-term infants on days 2-3. EEG sleep
      differences between preterm and full-term infants at matched postconceptional
      term ages are more likely to be due to conditions associated with prematurity
      rather than postnatal brain adaptation in the full-term group who experienced a
      more recent delivery.

PMID- 8552923
TI  - Prolactin and rapid eye movement sleep regulation.
AB  - During the past few years data have accumulated suggesting the involvement of
      prolactin (PRL) in rapid eye movement sleep (REMS) regulation. Pituitary PRL
      secretion seems to be, at least in part, sleep-dependent. PRL is also found in
      the central nervous system. PRL-containing neurons in the hypothalamus project to
      various structures in the brain. Systemic injection of PRL promotes REMS in rats,
      cats and rabbits. Intracerebroventricular injection of PRL enhances REMS in rats.
      Stimulation of endogenous PRL secretion by vasoactive intestinal peptide (VIP)
      also promotes REMS. Immunoneutralization of blood-borne PRL slightly reduces
      REMS. Various observations (hypoprolactinemic and hyperprolactinemic rats)
      indicate that PRL may act on REMS via modulating the diurnal rhythms of REMS. It
      is likely that hypothalamic PRL is more important for sleep regulation than
      circulating PRL. Hypothalamic PRL is likely involved in the mediation of the REMS
      promoting activity of VIP. We conclude that PRL has a role in REMS regulation.

PMID- 8552924
TI  - Temporal relationship between prolactin secretion and slow-wave electroencephalic
      activity during sleep.
AB  - It is well established that plasma prolactin (PRL) concentrations exhibit a sleep
      dependent pattern, with the highest levels occurring during sleep and the lowest
      during waking. Still, controversy exists concerning an association between rapid
      eye movement (REM) and non-REM sleep cycles and plasma PRL pulses. These studies
      were all based on conventional scoring of sleep stages. In the present study,
      plasma PRL concentrations were analyzed at 10-minute intervals in 10 subjects
      during the night when sleeping. PRL secretory rates were calculated by a
      deconvolution procedure. Spectral parameters of sleep electroencephalographic
      (EEG) recordings were analyzed together with PRL secretion using cross
      correlation. Slow-wave activity of the EEG and PRL secretion ran parallel in all
      individuals. Conversely, alpha and beta bands and the EEG mean frequency were
      inversely proportional to PRL secretion. In 9 of the 10 subjects studied, PRL
      secretion was concomitant with delta waves or lagged behind by 10-20 minutes,
      depending on subjects, with maximum cross-correlation coefficients ranging
      between 0.40 and 0.67. This temporal relationship between PRL secretion and delta
      waves was further assessed by a pulse-by-pulse analysis based on the calculation
      of probability levels after computer simulations. Nine of the 10 subjects
      displayed significant concomitance between delta wave activity and PRL secretory
      oscillations. These results demonstrate that PRL secretion during sleep is
      coupled to delta waves in young healthy men.

PMID- 8552925
TI  - Comparative effect of night and daytime sleep on the 24-hour cortisol secretory
      profile.
AB  - To determine whether cortisol secretion interacts with daytime sleep in a similar
      manner to that reported for night sleep, 14 healthy young men were studied during
      two 24-hour cycles. During one cycle they slept during the night, during the
      other the sleep period was delayed by 8 hours. Secretory rates were calculated by
      a deconvolution procedure from plasma cortisol, measured at 10-minute intervals.
      The amount of cortisol secreted during night sleep was lower than during the
      corresponding period of sleep deprivation (12.7 +/- 1.1 vs. 16.3 +/- 1.6 mg; p <
      0.05), but daytime sleep beginning at the habitual time of morning awakening
      failed to inhibit cortisol secretion significantly. There was no difference
      between the amount of cortisol secreted from 0700 to 1500 hours in sleeping
      subjects and in subjects who were awake during the same period of time (24.2 +/-
      1.5 vs. 22.5 +/- 1.4 mg). Even if the comparison between sleeping and waking
      subjects was restricted to the period 0700-1100 hours or 0700-0900 hours, no
      significant difference was found. Neither secretory pulse amplitude nor frequency
      differed significantly in either period. However, detailed analysis of the
      secretory rates in day sleepers demonstrated a transient decrease in cortisol
      secretion at about the time of sleep onset, which began 10 minutes before and
      lasted 20 minutes after falling asleep. Spontaneous or provoked awakenings had a
      determining influence on the secretory profiles. Ten to 20 minutes after
      awakening from either night or day sleep cortisol secretion increased
      significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8552926
TI  - Age and gender affect different characteristics of slow waves in the sleep EEG.
AB  - Low-frequency EEG was analyzed quantitatively during 2 nights in 40 females and
      34 males aged 26 to 101 years. Analyses were based on Rechtschaffen and Kales
      NREM sleep stages, on absolute low-frequency amplitude (i.e. power in the range
      of 0.2-2.0 Hz) and on low-frequency continuity. The latter parameter describes
      how much (0-100%) of the current slow-wave activity is continued in the near
      future EEG. Such continuation can occur through closed loops in the underlying
      neuronal network and cells. These loops are slow, thus corresponding to slow-wave
      frequencies, and can consist of electrophysiological, chemical and/or other
      pathways. The continuity percentage then monitors the relative activity of these
      loops. It does not depend directly on absolute EEG amplitudes. All analyzed
      parameters, including amplitude-independent continuity, decreased substantially
      and significantly with increasing age. The amplitudes of low-frequency EEG in
      females were significantly and substantially (40%) larger than those in males.
      However, the amplitude-independent continuity percentage did not differ between
      the genders. These findings support the notion that gender-related anatomical
      differences have a general effect on EEG amplitude, including during slow-wave
      sleep. Aging, however, specifically affects the neurophysiological slow-wave
      generating mechanism.

PMID- 8552927
TI  - The reliability of visual scoring of alpha EEG activity during sleep.
AB  - The reliability of visual scoring of alpha electroencephalogram activity in
      nonrapid eye movement sleep was evaluated. Three trained scorers independently,
      on two occasions, assessed one record from each of 10 patients. In addition to
      standard sleep staging of the records, alpha activity was scored using three
      methods: a) while the record was being scored, an assessment of alpha activity
      during the preceding stage was made at each stage change; b) after the record was
      scored a single global rating of alpha was made; and c) each 20-second epoch of
      the record was rated on the amount of alpha present. Relative and absolute
      generalizability coefficients in excess of 0.810 and 0.698, respectively, were
      obtained. However, the results also indicated that careful attention to
      methodological factors is critical in ensuring satisfactory standards of
      reliability.

PMID- 8552928
TI  - Localized and lateralized cerebral glucose metabolism associated with eye
      movements during REM sleep and wakefulness: a positron emission tomography (PET)
      study.
AB  - In order to study the neural substrate for eye movements during rapid eye
      movement (REM) sleep, we analyzed the positron emission tomography
      (18Fluorodeoxyglucose positron emission tomography) scan data obtained from
      normal subjects. Eye movement data were available on nine subjects studied during
      nighttime REM sleep and six control subjects studied during waking as they
      periodically moved their eyes. The number of eye movements during REM sleep was
      positively correlated with glucose metabolic rate in the areas corresponding to
      (a) the saccadic eye movement system (frontal eye field and dorsolateral
      prefrontal cortex, statistically significant only on the right side), (b) the
      midline attentional system (cingulate and medial frontal cortex, precuneus) and
      (c) the parietal visual spatial attentional system (bilateral superior parietal
      lobules, right inferior parietal lobule); and negatively correlated with relative
      metabolic rate in the left inferior parietal lobule. Positive correlations
      between waking eye movements and metabolic rate were observed in the same areas
      except inferior parietal lobule. Our results show that the same cortical areas
      are involved in eye movements in both REM sleep and wakefulness and suggest that
      REM sleep eye movements are saccadic scans of targets in the dream scene. Our
      data also suggest right hemispheric specialization in saccadic eye movement
      control and reciprocal inhibition in the contralateral homologous area during
      higher cortical functioning.

PMID- 8552929
TI  - 24-Hour metabolic rate in insomniacs and matched normal sleepers.
AB  - Groups of 10 objectively defined insomniacs and age-, sex- and weight-matched
      normal sleepers were evaluated on sleep, performance, mood, personality and
      metabolic measures over a 36-hour sleep laboratory stay. Insomniacs were defined
      to have increased wake time during the night but also had decreased stage 2 and
      rapid eye movement sleep. As expected insomniacs reported increased confusion,
      tension and depression and decreased vigor on the profile of mood states mood
      scale throughout the evaluation period as compared to the normals. Insomniacs
      also had decreased memory ability on the short-term memory test and the MAST.
      These performance and mood differences were not secondary to sleepiness because
      the insomniacs also had significantly increased multiple sleep latency test
      (MSLT) values throughout the evaluation period. In conjunction with the
      consistent mood, performance and MSLT differences during the day and the sleep
      differences at night, whole body VO2, measured at intervals across the day and
      throughout one night of sleep, was consistently elevated at all measurement
      points in the insomniacs as compared to the normals. The nocturnal increase in
      metabolic rate remained even after metabolic values from periods during the night
      containing wake time or arousals were eliminated from the data set. It was
      concluded that patients who report chronic insomnia may suffer from a more
      general disorder of hyperarousal (as measured here by a 24-hour increase in
      metabolic rate) that may be responsible for both the daytime symptoms and the
      nocturnal poor sleep. Future studies need to explore 24-hour insomnia treatment
      strategies that decrease hyperarousal.

PMID- 8552930
TI  - Prevalence of sleep disturbances among young adults in three European countries.
AB  - The aim of this investigation was to study the geographic variation in sleep
      complaints and to identify risk factors for sleep disturbances in three European
      countries: Iceland (Reykjavik), Sweden (Uppsala and Goteborg) and Belgium
      (Antwerp). The study involved a random population of 2,202 subjects (age 20-45
      years) who participated in the European Community Respiratory Health Survey. The
      subjects answered a questionnaire on sleep disturbances. Participants in Iceland
      and Sweden also estimated their sleep habits and sleep times during a period of 1
      week in a sleep diary. Habitual (> or = 3/week) difficulties inducing sleep (DIS)
      were reported by 6-9% and early morning awakenings by 5-6% of the subjects. The
      estimated number of awakenings and the prevalence of nightmares was significantly
      lower in Reykjavik. Participants in Reykjavik went to bed at night and woke in
      the morning approximately 1 hour later than participants at the Swedish centers
      (p < 0.001). Symptoms of gastroesophageal reflux (GER) were associated with DIS
      (odds ratio [OR] = 2.7), nightmares (OR = 4.4), longer sleep latency and frequent
      nocturnal awakenings. Smoking correlated positively to DIS (OR = 1.8) and
      estimated sleep latency. We conclude that the prevalence of DIS was fairly
      similar at these four European centers but that there was a variation in the
      prevalence of nightmares and nocturnal awakenings. The significant correlation
      between reported GER and subjective quality of sleep should be followed up in
      studies using objective measurements.

PMID- 8552931
TI  - Melatonin replacement therapy of elderly insomniacs.
AB  - Changes in sleep-wake patterns are among the hallmarks of biological aging.
      Previously, we reported that impaired melatonin secretion is associated with
      sleep disorders in old age. In this study we investigated the effects of
      melatonin replacement therapy on melatonin-deficient elderly insomniacs. The
      study comprised a running-in, no-treatment period and four experimental periods.
      During the second, third and fourth periods, subjects were administered tablets
      for 7 consecutive days, 2 hours before desired bedtime. The tablets were either 2
      mg melatonin administered as sustained-release or fast-release formulations, or
      an identical-looking placebo. The fifth period, which concluded the study, was a
      2-month period of daily administration of 1 mg sustained-release melatonin 2
      hours before desired bedtime. During each of these five experimental periods,
      sleep-wake patterns were monitored by wrist-worn actigraphs. Analysis of the
      first three 1-week periods revealed that a 1-week treatment with 2 mg sustained
      release melatonin was effective for sleep maintenance (i.e. sleep efficiency and
      activity level) of elderly insomniacs, while sleep initiation was improved by the
      fast-release melatonin treatment. Sleep maintenance and initiation were further
      improved following the 2-month 1-mg sustained-release melatonin treatment,
      indicating that tolerance had not developed. After cessation of treatment, sleep
      quality deteriorated. Our findings suggest that for melatonin-deficient elderly
      insomniacs, melatonin replacement therapy may be beneficial in the initiation and
      maintenance of sleep.

PMID- 8552932
TI  - A familial awake movement disorder mimicking restless legs in a sleep apnea
      patient.
AB  - We report on a patient with sleep apnea and an unusual familial movement
      disorder. The movements were present only during wakefulness and nocturnal
      arousals caused by disordered breathing. A 27-year-old obese man was referred
      with sleep onset insomnia, symptoms suggesting restless legs syndrome, daytime
      sleepiness, loud snoring and awakening with choking sensations. He was proven to
      have obstructive sleep apnea (apnea hypopnea index = 60.6). He also had a daytime
      movement disorder that was characterized by almost continuous stereotypic tapping
      of one or both legs. The movements were suppressible and not associated with any
      unpleasant or abnormal leg sensation. Virtually identical movements were present
      in three generations of his family. The severity of the movements did not worsen
      late in the day or with supine posturing. The nocturnal movements, consisting of
      a visible shaking of one or both legs, occurred only during arousals secondary to
      the apnea, had a mean duration of 5.7 +/- 3.0 (standard deviation) seconds and
      could not be defined as periodic limb movements in sleep (PLMS). Successful
      treatment of apnea by nasal continuous positive airway pressure dramatically
      reduced the movements during sleep (from 88.2 to 1.9 per hour). The clinical
      significance and the mechanism of this movement disorder is unknown. We discuss
      the features inconsistent with restless legs syndrome and consider other possible
      phenomenology, including akathisia. We conclude that this patient may have a
      previously unreported familial movement disorder and in addition developed the
      sleep apnea syndrome related to obesity.

PMID- 8552933
TI  - Elimination of a rhythmic movement disorder with hypnosis--a case report.
AB  - The following describes a case of rhythmic movement disorder successfully treated
      with hypnosis. Hypnosis and its use in sleep disorders are discussed, and it is
      hypothesized that hypnosis is an effective intervention in disorders that occur
      at the interface between waking and sleep.

PMID- 8552934
TI  - Bibliography of recent literature in sleep research.

PMID- 8552935
TI  - [Education as a process for change in organizations and in people].

PMID- 8552936
TI  - [Psycho-physical evaluation of the elderly. The scales used].

PMID- 8552937
TI  - [A typical cervical vertebra].

PMID- 8552938
TI  - [The helping relation in hospital admission].

PMID- 8552939
TI  - [Preventive measures. Dental care for pregnant women].

PMID- 8552940
TI  - [Fenny Boerema, expert in haptonomy. Haptonomy is the science of touch].

PMID- 8552941
TI  - [Health psychology in the new curriculum for the nursing diploma].

PMID- 8552942
TI  - [Cranio-encephalic injuries. A comparative study].

PMID- 8552943
TI  - [Treatment of varicose ulcers in nursing practice].

PMID- 8552944
TI  - [Surgical flaps to cover injured legs].

PMID- 8552945
TI  - [Localization of infectious foci. More efficient by leukocyte marking].

PMID- 8552946
TI  - [Manual cardiac compressor. An apparatus for the active compression-decompression
      in cardiopulmonary resuscitation].

PMID- 8552947
TI  - Ethics in action. The surgeon chooses not to come to the hospital.

PMID- 8552948
TI  - Restoring electrolyte balance. Sodium & chloride.

PMID- 8552949
TI  - New trends in thrombolytic therapy.

PMID- 8552950
TI  - We don't chase down doctors anymore.

PMID- 8552951
TI  - This dementia patient can be helped.

PMID- 8552952
TI  - Patient-centered care?

PMID- 8552954
TI  - Where the nurse can really work up a sweat.

PMID- 8552953
TI  - Radiation therapy: protecting your patient's skin.

PMID- 8552955
TI  - If equipment causes injury.

PMID- 8552956
TI  - A serious side effect for a commonly prescribed antibiotic.

PMID- 8552957
TI  - Living wills: not just for the elderly.

PMID- 8552958
TI  - [Prof. Dr. Hab. Maksyn Nikonorowin the memory of his colleagues].

PMID- 8552959
TI  - [The main ecological hazards of food. 1990].

PMID- 8552960
TI  - [Maksym Nikonorow--10th anniversary of death].

PMID- 8552961
TI  - Evaluation of food safety.
AB  - In evaluation of food safety, microbiological and physico-chemical requirements
      are taken into consideration. Food safety assurance is carried out attained by
      toxicological evaluation of substances present in food, determination of its
      acceptable (ADI) or tolerable (PTWI or PMTDI) levels for human and adequate legal
      regulations.

PMID- 8552962
TI  - [Content of lead, cadmium, mercury, zinc and copper in fruit from various regions
      of Poland].
AB  - The content of lead, cadmium, mercury, zinc and copper was determined in various
      species of fruit gathered in Poland in the period 1989-1991. Samples for the
      determinations were taken from regions not directly exposed to air pollution from
      industrial plants and traffic. The content of Pb, Cd, Zn and Cu was determined
      after dry mineralization (at about 400 degrees C) by the flame ASA technique: Cu
      and Zn were determined directly in mineralizate solution, Pb and Cd after
      extraction of their complexes with APDC; Hg after wet mineralization by flameless
      ASA "cold vapour" method. About 10000 samples of fruit and about 300 samples of
      soil from the sites where the fruit was collected were investigated. The highest
      lead levels were found in strawberries, raspberries and currants (about 0.1 mg/kg
      on average), cadmium in raspberries and strawberries (mean 0.02 mg/kg). Mercury,
      zinc and copper levels were low. The levels of all these metals were lowest in
      apples and pears (Pb-mean 0.010-0.089 mg/kg, Cd mean 0.001-0.006 mg/kg, Cd mean
      0.001-0.006 mg/kg). The content of metals in fruit, but ever more in soil, from
      highly industrialized areas was significantly higher. The authors suggest
      lowering in the Polish legislation of the maximal acceptable lead concentration
      in all types of fruit down to 0.20 mg/kg, and cadmium to 0.03 mg/kg for all types
      of berries and 0.02 mg/kg for the remaining fruit types.

PMID- 8552963
TI  - [Residues of antibiotics and other inhibitory substances in milk].
AB  - The aim of the study was determination of the contamination of raw milk, milk for
      consumption and powdered milk with antibiotics and inhibitory substances. The
      study was carried out in the years 1990-1993 with the assistance of the Province
      Sanitary-Epidemiological Stations using methods agreeing with the Polish Norms
      91/A-86033: the enzymatic test Penzym, the microbiological tests S.STD Polulest
      and the plate method. In all, 16334 samples were tested. Depending on the method
      used the number of positive samples was: in raw milk: from 13.1 to 22.4% in milk
      for consumption: from 10.5 to 19.5% in powdered milk: from 12.9 to 18.2%. These
      results point out that the health quality of milk is insufficient, both milk for
      processing and milk in the market failing to meet the standards. The source of
      the seem to be inadequate hygienic conditions during milking and, especially,
      failure to meet the necessary requirements for keeping the time period during
      which milk is not suitable for consumption after treatment with antibiotics.

PMID- 8552964
TI  - [Level of histamine and tyramine in ripening cheeses].
AB  - Histamine poisoning is a foodborne chemical intoxication resulting from the
      ingestion of food products containing high levels of histamine. Historically,
      histamine poisoning has been attributed to the consumption of fish species
      belonging to the Scomberesocidae and Scombridae families and other sea fish, but
      histamine poisoning outbreaks may occur after the consumption of cheese, or other
      types of fermented foods. Also tyramine has been proved as a cause of adverse
      reactions, involving headache, hypertensive crisis and interactions with
      antidepressive drugs, which were observed after consumption of ripening cheeses.
      The formation of high levels of histamine and tyramine in foods is directly
      correlated to the level of microorganisms, possessing the enzymes: histidine and
      tyrozyne decarboxylases, and also with the concentration of histidine and
      tyrosine free substrate. Proteolysis, which takes place during ripening of
      cheeses may play role in the release of free histidine and tyrosine. This study
      reports on the levels of histamine and tyramine in ripening cheeses taken from
      Polish food market. 43 samples of soft and hard cheeses were investigated.
      Histamine was measured according to the AOAC fluorometric method. Tyramine was
      measured after column separation and purification, according to the
      spectrofluorometric technique with 1-nitroso-2-ortophtalate aldehyde, according
      to Carou with couple of modifications by authors. Histamine levels ranged from 0
      to 157 mg/kg and tyramine levels ranged from 3.8 to 575 mg/kg. The very high
      levels of histamine and tyramine in many samples of cheeses support the opinion,
      that sometimes the storage temperature has not been sufficient to stop bacterial
      multiplication and in consequence enzymatic activity of decarboxylases of native
      amino acids--precursors of biogenic amines in ripening cheeses.

PMID- 8552965
TI  - [Microbiological quality of food].
AB  - The per cent values are reported of the samples of certain food products taken in
      1982-1994 for evaluation of their compliance with the present standards of
      microbiological quality which failed to meet these standards. The data on the
      contamination of food products and the incidence of food poisonings are regarded
      as disquieting. Although some improvement has been achieved in recent years, the
      present situation indicates that no further improvement has been noted and even
      some deterioration of the microbiological quality of food products has occurred.

PMID- 8552966
TI  - [Nitrilotriacetic acid (NTA)--properties, distribution and behavior in the
      environment. I. Chemical and toxicological properties of NTA].
AB  - The reason of the interest shown in the properties of NTA is the possibility of
      its use for the replacement of polyphosphates in washing powders which are the
      cause of water eutrophization. In the light of literature data the chemical
      properties of NTA and the conditions influencing the course of the reaction of
      complex formation with metal ions in aqueous solutions are discussed Equilibrium
      constants of these reactions are presented, with diagrams obtained in computer
      assisted analysis of the conditions of equilibrium of NTA reaction with metal
      ions in the solutions occurring in physiological conditions and in the
      environment. On the basis of the opinions of expert committees the toxicity of
      NTA for mammalian organisms are described. It has been shown that NTA has no
      teratogenic or mutagenic action, however, in 2-year observations of mice and rats
      the intake of NTA produced lesions of uroepithelium with development of tumours.
      This effect of NTA has been demonstrated to be closely connected with its
      property of complex formation with metal ions. Experiments are described in which
      confirmation was obtained of the hypothesis that pathological lesions of renal
      tabules are caused by accumulation of zinc and bladder tumours are caused by
      binding by NTA of calcium from epithelial cells.

PMID- 8552967
TI  - [Formaldehyde determination in shampoos, bath preparations and dish washing
      liquids by colorimetric methods].
AB  - In the years 1992-1993 in cooperation with Province Sanitary-Epidemiological
      Stations 2415 samples of shampoos and bath preparations for adults and children
      as well as of dish washing liquids, imported and produced in Poland, were
      analysed. The colorimetric method either with the chromotropic acid or
      acetylacetone was used. Among polish preparations, only in 6% samples of cosmetic
      products for children the level of formaldehyde exceeded permitted level of 50
      mg/kg. In all cosmetic products for adults as well as in all samples of dish
      washing liquids the content of formaldehyde was below permitted level 500 mg/kg.
      Among imported products, 40% of samples of cosmetics for children, 3%--for adults
      and 2% of dish washing liquids revealed formaldehyde level above permitted
      values. It is advisable to determine periodically formaldehyde content in
      particular cosmetic products, such as shampoos and bath preparations, mainly used
      by children.

PMID- 8552968
TI  - [A method for determining global migration into model fluids from plastic
      packaging materials, in accordance with recommendations of the EWG commission].
AB  - Samples of polypropylene, polyethylene, polystyrene foils, softened polyvinyl
      chloride foils and laminates, in which polyethylene or EVA copolymer or SULRYN
      ionomer formed the inner layer were subjected to tests for determination of the
      global migration to aqueous fluids using model methods: chamber test, bag test,
      immersion test and lining test. The tested materials comprised 37 samples of
      packaging materials. The tested samples were not exceeding the range of permitted
      global migration into aqueous model fluids as recommended by the EEC directives.
      The obtained results fell significantly below the accepted limit of 10 mg/dm2.

PMID- 8552969
TI  - [Abiotic and biotic transformation of persistent organochlorine compounds in the
      environment].
AB  - The presence of persistent organochlorine compounds in the environment is defined
      as being of anthropogenic origin. They are the result of intentional production
      (pesticides, solvents, dielectric and hydraulic fluids, flame retardants etc.) as
      well as they are produced as unintentional by-products from many processes
      (incineration, pulp and paper production, use and production of chlorinated
      aromatic chemicals and PVC). Nowadays, they are recognized as one of the major
      classes of the contaminants in the environment because of their wide distribution
      and a high capacity to bioaccumulate in organisms--especially in higher levels of
      the trophic food chain. They have been also claimed to cause adverse effects on
      organisms and human. In the paper, the main classes of chlorinated hydrocarbons
      are presented, including pesticides, polychlorinated biphenyls and dioxins. The
      proposed degradative pathways--abiotic (photolysis, hydrolysis) as well as biotic
      (biotransformation by microorganisms and higher organisms, including human) are
      reviewed on the basis of current literature.

PMID- 8552970
TI  - [Laboratory examination of the effectiveness of new biological preparations for
      reducing populations of cockroaches (Blattella germanica L.)].
AB  - The usefulness of new commercial products of biological origin (Biobit, Novo
      Skeetal and Novodor) was tested in cockroaches (Blattella germanica L.) control.
      Biobit proved to be the most effective in reduction of cockroaches population.
      Its higher activity against cockroaches was observed in all concentrations
      tested. Females were more sensitive for all tested products than males.

PMID- 8552971
TI  - [The influence of load size on the result of ethylene oxide gas sterilization].
AB  - The purpose of the study was establishing whether the size of the load--that is
      the degree of filling of sterilizer chamber with medical instruments--could have
      an effect on the time needed for eradication of all microorganisms subjected to
      the action of ethylene oxide. The test organism used was the strain of Bacillus
      subtilis var. niger ATTC 9372. Tests were prepared with about 3.6 x 10(6) spores
      per one test. The tested samples were exposed to ethylene oxide at concentration
      of 750 mg/l, at 50-80 degrees C, at 40% humidity during 30, 60, 120, 180, 240 and
      300 minutes in three variants: in empty sterilizer chamber im chamber loaded with
      plastic objects (polyethylene and polypropylene)--600 g weight in chamber with
      similar load weighing 1200 g. The obtained results showed that the degree of
      filling of sterilizer chamber influenced the efficiency of gas sterilization with
      ethylene oxide. The effectiveness of each sterilization process with ethylene
      oxide should be controlled using biological indicators.

PMID- 8552972
TI  - [Determination of the acoustic climate inside elementary schools].
AB  - The evaluation of acoustic conditions in four elementary schools showed high
      levels of noise inside schools, especially in corridors. It refers mainly public
      schools, which generally are overcrowded. During breaks the most frequent noise
      level is 86 dB but in some parts of corridors approaches values 95-98 dB. During
      lessons the noise in corridors decreases to about 64 dB. However during physical
      exercises which take place in corridors the noise level in corridors increases up
      to 75-80 dB. In public schools the noise levels in corridors both during lessons
      and breaks are higher about 12 dB than in private schools. However during lessons
      in classrooms those differences are quite lower. The noise level during lessons
      depends mainly on number of pupils, subject of the lesson, year of schooling and
      period of duration of the lesson. Considerable growth of noise occurs in classes
      above 20 pupils and at initial and final period of the lesson. The most
      favourable acoustic conditions are in classes below 15 pupils but in classes
      above 20 pupils the noise levels increase average about 4 dB. In spite of common
      opinion the noise level is lower in classes with younger children than in classes
      with older children. In older classes the noise is higher average about 3 dB. The
      noise in classroom depends also on manner of teaching and type of tasks performed
      by schoolchildren. The work in group is noisiest (average more 8 dB than during
      lectures). It refers especially to gymnastics lessons during group games. In this
      case the noise levels usually are above 90 dB. However it was not observed
      significant differences in daily or weekly distribution of the noise level during
      lessons. Resultant daily noise exposure of schoolchildren during their school
      time is 80 dB (or sometimes 85 dB) in public schools and 72 dB in private
      schools. Average noise exposure in public schools approaches critical values
      accepted for hearing protection for adolescents during apprenticeship.

PMID- 8552973
TI  - Development of a short scale for self-assessment of experiences of hearing loss.
      The hearing coping assessment.
AB  - A short scale for self-assessment of experiences of hearing impairment--the
      Hearing Coping Assessment (HCA) was developed and administered to 114 consecutive
      hearing-impaired patients at a Swedish hearing centre. The scale was evaluated in
      terms of descriptive statistics, reliability, principal components analysis, and
      validity. The results showed high internal consistency, high split-half
      correlation, and high item-total correlations. Significant correlations were
      found between the HCA questionnaire and measures of optimism, depressive
      syndrome, and audiogram (PTA). The principal component analysis showed two
      meaningful factors. The first mainly represents disability, and the second
      emotional reactions due to hearing loss. Aspects of handicap were present in both
      factors. The subjects in this study were no less optimistic nor did they show
      more signs of depressive syndrome than comparable norm groups. Still, optimists
      reported fewer hearing problems as measured by the HCA. The HCA is proposed as a
      suitable assessment scale in studies on the effects of counselling.

PMID- 8552974
TI  - Clinical application of distorted speech audiometry.
AB  - The clinical validity of four different low-redundant speech tests was calculated
      using four groups of 83 patients with retrocochlear or central auditory lesions.
      The speech tests used were: interrupted speech (7 or 10 interruptions/s) time
      compressed speech and filtered speech. A comparison between patients and age
      matched normal-hearing controls showed that the patients had significantly lower
      speech recognition score. The best sensitivity ratings of the tests were between
      47% and 80%, the highest in patients with cerebellopontine angle tumours and
      temporal lobe lesions, and the lowest in vascular brainstem lesions. The speech
      tests with the highest sensitivity were 7 interruptions/s and time-compressed
      speech.

PMID- 8552975
TI  - Calibration of ipsilateral stimulus transducer for acoustic reflex measurements.
AB  - Pure-tone Reference Equivalent Threshold Sound Pressure Level (RETSPL) of the
      ipsilateral stimulus receiver for acoustic reflex measurements on Madsen
      Electronics type Zodiac 901 impedance audiometer is provided. The results,
      obtained from 20 normal-hearing subjects, are achieved by comparing hearing
      threshold levels measured using a TDH 39 telephone (calibrated to ISO 389) with
      thresholds recorded using the ipsilateral stimulus insert phone. The calibration
      is referenced to an IEC-711 ear simulator and comprises the following
      frequencies: 125, 250, 500, 750, 1000, 1500, 2000, 3000, 4000, 6000, 8000 Hz.

PMID- 8552976
TI  - Effect of contralateral white noise masking on the mismatch negativity.
AB  - Mismatch negativity (MMN), an auditive event-related potential (ERP) component,
      evoked by deviant stimuli in a homogeneous stream of standard stimuli was studied
      in a unilateral stimulation and contralateral white noise masking condition.
      Eleven subjects (Ss) with normal hearing (aged 20-35 years) were examined using
      sine tone stimuli (70 dB HL, interstimulus interval 300 ms, duration 40 ms with 5
      ms rise and fall times). Three blocks of standard (std)/deviant (dev) series of
      stimuli were used: std 500/dev 600 Hz, std 2000/dev 1900 Hz, and std 2000/dev
      1600 Hz. The first block was repeated for another group of 11 Ss with normal
      hearing (aged 17-27 years). The MMN was analysed from the difference curves
      recorded at Fz, Cz and Pz. The stimuli were delivered unilaterally, either with
      or without 50 dB effective masking level white noise to the contralateral ear.
      The MMN amplitude attenuated significantly when contralateral masking was used.
      In addition, there was interaction between noise masking and the stimulated ear.
      The MMN latencies were not affected by white noise masking.

PMID- 8552977
TI  - Consonant perception with linear and compression amplification.
AB  - The consonant perception of 15 subjects with mild to moderate sensorineural
      hearing loss was evaluated using linear amplification and two different types of
      compression amplification. A specially modified hearing aid was used which
      allowed for variation of the amplifier input/output function in three steps, such
      that the compression ratio could be set to 1 (linear), 1.3 or 1.8. The Nonsense
      Syllable Test (NST) was recorded through the aid in quiet and in two different
      noise conditions (four-talker babble and a background noise with sharp
      intermittent sounds), and replayed to the listeners through headphones. No
      differences in consonant perception were found between the different types of
      amplification in the quiet condition. In the babble condition, consonant
      perception was significantly better with linear amplification than with either
      form of compression. In the sharp noise condition, there was no difference in
      performance between linear amplification and compression amplification with the
      ratio of 1.8. Consonant perception was adversely affected, however, by the
      compression and amplification with the ratio of 1.3 in this condition. Overall
      NST results and results for particular classes of consonants are discussed.

PMID- 8552978
TI  - Auditory brainstem response to bone-conducted clicks in adults and infants with
      normal hearing and conductive hearing loss.
AB  - Knowledge concerning auditory brainstem response (ABR) by bone conduction (BC) is
      limited, and occasionally controversial. The present study was aimed at further
      elaboration of this issue. The research population consisted of 107 subjects.
      Four groups were investigated: group 1, normal-hearing adults aged 20-37 years;
      group 2, 10 children aged 5.6-8.4 years, with confirmed middle ear effusion
      (MEE); groups 3 and 4, 22 infants, matched by pairs, aged 5-18 months, 11 with
      normal otoscopy and 11 with suspected MEE. Comparison between ABR by AC and BC
      for all four groups is discussed. We observed that the AC-ABR threshold of group
      2 was statistically significantly elevated compared to group 1. The same tendency
      was observed for group 4 compared to group 3. In AC ABR, the mean latency of wave
      V was significantly prolonged, compared to that of BC ABR in children with
      confirmed MEE, and infants with suspected MEE. We strongly suggest that by
      combining AC and BC ABR, more information concerning cochlear reserve status can
      be obtained in infants and young children who are difficult to test, or wherever
      a behavioral audiogram cannot be achieved.

PMID- 8552979
TI  - Speechreading instruction for hard-of-hearing adults. Effects of training face-to
      face and with a video programme.
AB  - The effects of speechreading instruction were studied using a structurally
      planned training programme in two types of situations: in a face-to-face
      situation and by using videotapes viewed at home. Instruction was given only
      visually. Three speechreading tests were selected to monitor the efficacy of
      training: CID sentences. Helen questions and the tracking method. Two of the
      tests (CID and Helen) showed significant improvement in all three groups training
      speechreading. The tracking method, however, did not prove to be a reliable
      method for assessing the performance of a large group of subjects. The
      performances of the face-to-face groups and the video group did not differ
      significantly. The present study showed that training speechreading is
      advantageous and confirmed the effectiveness of tutored self-instruction at home.

PMID- 8552980
TI  - Ipsilateral acoustic reflex thresholds at varying click rates in humans.
AB  - The effects of the click repetition rates on the ipsilateral acoustic reflex
      thresholds were investigated in 17 normal female subjects (total 34 ears) within
      the age-range of 20 to 26 years. The acoustic reflexes were elicited in response
      to condensation clicks (100 microseconds duration) at repetition rates of 50,
      100, 150, 200, 250 and 300/sec. The probe tone frequency was 226 Hz and the
      intensity was 85dB SPL. The thresholds improved significantly with increase in
      the repetition rates. The mean threshold advantage was 11.2dB with an increase in
      the rate from 50 to 100/sec, it was 7.8dB when the rate was increased from 100 to
      200/sec and was further reduced to 2.6dB when the rate was increased from 200 to
      300/sec. These findings are discussed with reference to the temporal and the
      spatial summation and facilitation. Possible clinical implications of the
      findings are presented.

PMID- 8552981
TI  - High expression of membrane cofactor protein of complement (CD46) in human
      leukaemia cell lines: implication of an alternatively spliced form containing the
      STA domain in CD46 up-regulation.
AB  - Human membrane cofactor protein (MCP, CD46) is a receptor for the measles virus
      and serves as a complement regulator which protects host cells from autologous
      complement attack. MCP is highly polymorphic due to a variety of mRNA splice
      products. The levels of MCP expression on T and myeloid cell lines are usually
      two-eightfold higher than those on their normal counterparts, whereas Burkitt's
      lymphoma B cell lines express less MCP than B cell lineages carrying no EB virus.
      The molecule has a Ser/Thr-rich (ST) domain adjacent to the functional domain,
      namely short consensus repeats (SCR). The ST domain and a cytoplasmic tail (CYT)
      contribute to the MCP polymorphism. The ST domain is encoded by three exons (A, B
      and C) and major ST isoforms are STABC, STBC and STC. The authors investigated
      the relationship between the expression levels and isoform usage of MCP by flow
      cytometry using specific antibodies against STA and STC, by reverse transcriptase
      polymerase chain reaction (RT-PCR) with size markers for each splice variant, and
      by RT-PCR/Southern blotting using a specific probe for STA. The results were (1)
      the profiles of mean shifts of myeloid and T cell lines were STC < STA on flow
      cytometry while those of B cell lines and normal blood cells were STA < STC; (2)
      all cell lines tested by RT-PCR expressed the messages for the isoforms
      STBC/CYT1, STC/CYT1, STBC/CYT2, and STC/CYT2. The band for STABC/CYT2 overlapped
      that for STC/CYT1, and the band for STABC/CYT1 was marginal in all cell lines
      examined; (3) semi-quantitative analysis of the STABC isoforms by Southern
      blotting indicated the presence of high levels of the STABC messages in myeloid
      and T-cell lines in comparison with B lymphoid cells and normal leucocytes. Thus,
      the quantity of MCP expressed parallels the STABC message level, which is up
      regulated in T and myeloid leukaemia cell lines.

PMID- 8552982
TI  - Specific interferon-gamma producing CD4+ and CD8+ T cells after autologous EBV-B
      stimulation: the necessity of restimulation.
AB  - The response of T cells to produce interferon-gamma, to proliferate and to become
      cytotoxic after specific stimulation with low dose (2%) autologous EBV-B cells
      was investigated in 15 EBV seropositive and five seronegative patients. A
      significantly higher number of interferon-gamma producing cells (56 +/- 24 per
      10(5) T cells) were found in a spot ELISA in EBV positive than in EBV negative
      patients (7 +/- 2 spots, P < 0.01) and it was only found with restimulation after
      5-12 days of primary culture. No correlation was found between the extent of
      interferon-gamma production, cytotoxicity or proliferation. Specificity of EBV
      induced interferon-gamma production was demonstrated by comparison of the
      response to allogeneic EBV-B cells or IL-2 in the restimulation phase. The
      response was stronger in CD8+ T cells than in CD4+ T cells and could be blocked
      in the restimulation phase with HLA class I and class II antiserum, respectively.

PMID- 8552983
TI  - Differential patterns of T-cell receptor BV-specific activation of T cells by
      gp120 from different HIV strains.
AB  - Studies by several groups have suggested that HIV infection in vivo results in a
      BV-specific alteration of the TCR repertoire and that this might play a role in
      the pathogenesis of AIDS. Our earlier studies demonstrated that both a crude
      extract of HIV451 as well as purified gp 160 from HIV451 could specifically
      activate, in vitro, T cells expressing a common set of TCRBV segments (TCRBV3,
      12, 14, 15, and sometimes BV17 and 20) in individuals of disparate HLA type.
      Furthermore, purified gp120 from HIV451 was shown to have a similar ability to
      activate T cells, although with a slightly different TCRBV-specific pattern. In
      order to determine whether gp120 from other HIV strains could similarly activate
      T cells in a TCRBV-specific pattern, PBMC from HIV seronegative individuals of
      disparate HLA type were stimulated with gp120 from three strains of HIV (451,
      IIIB, and MN). The authors found that gp120 from all three strains activate T
      cells bearing TCRBV2 and BV3 in nearly every individual. T cells expressing other
      BV segments are also activated, but this is more variable and appears to be
      unique to each individual. Furthermore, gp120(451) and gp120 from HIVIIIB and
      HIVMN differ in their ability to activate T cells expressing these other TCRBV
      segments. These observations suggest that variation in the structure of gp120 and
      in the genetic and/or environmental background of the individual play an
      important role in determining which TCRBV segments are 'triggered' by gp120.
      Furthermore, these observations may have important implications for the rate of
      disease progression in HIV-infected individuals.

PMID- 8552984
TI  - Engraftment and humoral immunity in SCID and RAG-2-deficient mice transplanted
      with human peripheral blood lymphocytes.
AB  - SCID and RAG-2 deficient mice were transplanted intraperitoneally with human
      peripheral blood lymphocytes (hu-PBL-SCID and hu-PBL-RAG mice). Seven days after
      transplantation the mice were immunized with a pneumococcal polysaccharide
      vaccine. Flow cytometry analysis of cells from the peritoneal cavity and the
      spleen after 8-10 weeks revealed that human cells had more limited engraftment in
      RAG than in SCID recipient mice, and that more human cells were found in the
      spleen than in the peritoneal cavity. Functionality of the human cells recovered
      from these two locations was explored by the counting of human immunoglobulin
      secreting cells (hu-ISC). A total of 83% of the hu-PBL-SCID mice and 29% of the
      hu-PBL-RAG mice had detectable hu-ISC in the peritoneal cavity and/or the spleen.
      The kinetic profiles of human immunoglobulins in the mouse sera during the
      experiment showed donor dependency. More than 90% of the hu-PBL-SCID mice had
      detectable levels of human IgG, IgM and IgA, while 78% had detectable levels of
      IgE, whereas detectable levels of IgG, IgM, IgA and IgE were measured in 37%,
      64%, 68% and 23% of the hu-PBL-RAG mice, respectively. Forty-seven per cent of
      immunized hu-PBL-SCID mice showed a human antipneumococcal IgG level that was
      significantly above the background level in non-immunized mice, while none of the
      hu-PBL-RAG mice produced any detectable levels of human antipneumococcal IgG. In
      short, human PBL showed a better engraftment and a better antibody response when
      transplanted into SCID mice than into RAG mice.

PMID- 8552985
TI  - The antibody response to secondary immunization with pneumococcal polysaccharides
      in mice.
AB  - The benefit of re-immunization with pneumococcal polysaccharide vaccine is an
      important question in clinical practice. In an experimental model, BALB/c and
      CBA/J mice were re-immunized s.c. with a 23-valent pneumococcal polysaccharide
      vaccine at various time intervals after a first immunization with the same
      vaccine. The antibody response after the secondary immunization showed similar
      kinetics as after primary immunization, and was mainly an IgM antibody response.
      Re-immunization at 28 days or earlier induced a decrease in the serum antibody
      levels to the vaccine. Reimmunization at 120 days or later induced higher
      antibody levels than after the first immunization. Significant increases in
      antibody levels to serotypes 1, 4, 7F and 19F out of six serotypes tested were
      observed. In CBA/J mice, but not in BALB/c mice, the dose used for primary
      immunization appeared to influence the magnitude of the antibody response to
      secondary immunization. Our results indicate that the time interval between
      primary and secondary immunization is an important determinant with regard to the
      magnitude of the antibody response to re-immunization with pneumococcal
      polysaccharide vaccine.

PMID- 8552986
TI  - Adhesion of Plasmodium falciparum-infected erythrocytes to human cells and
      secretion of cytokines (IL-1-beta, IL-1RA, IL-6, IL-8, IL-10, TGF beta, TNF
      alpha, G-CSF, GM-CSF.
AB  - The scientific interest in the physical interaction of Plasmodium falciparum
      infected erythrocytes with host cells stems from the suggestion that excessive
      binding in the microvasculature leads to severe malaria. The authors studied,
      therefore, two parasites for their ability to adhere to normal human cells and to
      induce cytokine production, one parasite lacking a binding capacity (DD2) and one
      which adhered to CD36+ transfected CHO cells (MCAMP). The MCAMP parasites readily
      bound to platelets and erythrocytes and to monocytes, polymorphonuclear
      granulocytes and EBV-transformed B cells as seen by light and electron
      microscopy. Platelets were frequently attached in large numbers to the infected
      erythrocyte surface and groups of infected erythrocytes were sometimes held
      together by several platelets. Nine out of 17 cytokines tested were found to be
      secreted into the culture supernatants after 35 h of co-cultures containing
      monocytes or unfractionated peripheral blood mononuclear cells (PBMC) and
      parasites (IL-1RA, IL-6, IL-8, IL-10, TGF beta, TNF alpha, G-CSF, IL-1-beta, and
      GM-CSF). Three additional cytokines were also present in low levels (< 200 pg/ml,
      IL-2, IL-4, IFN gamma) in the culture supernatants after incubation of the cells
      for 4 days. TNF alpha, IL-RA, and IL-8 were secreted from polymorphonuclear
      granulocytes, LGLs and T cells. Platelets and, to a lesser degree, monocytes and
      T cells secreted large amounts of TGF beta (10-30 ng/ml). Cytokines may
      participate in the pathogenesis but also the suppression of immune responses seen
      during acute malarial infections.

PMID- 8552987
TI  - Schistosoma mansoni in the baboon: modulation of pathology after vaccination with
      polyclonal anti-idiotypic antibodies.
AB  - Vaccination of five baboons with an anti-idiotypic vaccine to irradiated
      Schistosoma mansoni cercariae resulted in nearly 19% protection compared to 39%
      protection conferred to five baboons vaccinated with an irradiated vaccine.
      Vaccination with the anti-idiotypic antibodies resulted in a significant
      reduction of pathology and granuloma size following challenge with live
      unattenuated cercariae. Results presented in this work are considered highly
      significant because the anti-idiotypic vaccine markedly influenced
      schistosomiasis morbidity which is the main consideration in this disease.

PMID- 8552988
TI  - Immunoparasitological studies of Trypanosoma cruzi low virulence clones from
      Panama: humoral immune responses and antigenic cross-reactions with Trypanosoma
      rangeli in experimentally infected mice.
AB  - The kinetics of humoral immune responses were investigated in mice experimentally
      infected with five clones of Trypanosoma cruzi isolated from different sources in
      Panama. Sera were collected at different timepoints post-infection. ELISA and IHA
      tests were used to detect antibodies against T. cruzi epimastigote antigens. The
      levels of T. cruzi specific antibodies increased during the course of infection;
      at day 90 post-infection the range was between 1:5120 and 1:10240. A high
      correlation was evident between ELISA and IHA results. Western blots revealed
      that these antibodies recognized polypeptides of 81, 76 and 71 KDa during the
      first weeks and 81, 76, 71, 50, 40, 28 and 12 KDa after 30-50 days. Only minor
      differences in antigen recognition patterns were demonstrated, suggesting that
      the major antigens may be represented in all clones. T. rangeli antigens were
      also recognized by T. cruzi seropositive sera. However, an ELISA test using
      antigens isolated from a genomic expression library of T. cruzi revealed that a
      hyperimmune rabbit serum against T. rangeli was unable to recognize the repeat
      sequence of SAPA (Shed Acute Phase Antigen) peptides but did recognize a number
      of other T. cruzi synthetic peptide antigens. The importance of these findings,
      in the context of Chagas' disease, is discussed.

PMID- 8552989
TI  - Preferential positive selection of T lymphocytes which express two different TCR
      alpha chains, an endogenous and a transgenic.
AB  - A hallmark of positive selection in T-cell receptor (TCR)-transgenic mice is a
      strong skewing towards the CD4+ or the CD8+ subset, depending on the class II or
      I restriction of the TCR, respectively. However, previous experiments in TCR
      transgenic mice specific for an Ig light chain (lambda 2(315)/I-Ed class II
      molecule did not fit into this scheme because the authors observed an anomalous
      skewing towards CD8. In this paper the authors show that endogenous TCR alpha
      chains are expressed on > 90% of CD4+ and CD8+ cells in this particular
      transgenic strain, even on a selecting H-2d haplotype. Endogenous TCR alpha
      chains are first detected when double-positive thymocytes down-regulate either
      CD4 or CD8. Endogenous V alpha seems to influence generation of T-cell subsets
      because CD4+ and CD8+ cells express different frequencies of endogenous V alpha 2
      and V alpha 8. In the absence of endogenous TCR alpha chains in recombination
      deficient TCR-transgenic severe combined immunodeficiency (SCID) mice, a strong
      skewing towards CD4+ T cells is seen, but such mice are severely T-cell
      deficient. As an explanation for these results, the authors suggest that the
      transgenic TCR has a too low affinity for efficient positive selection,
      therefore, TCR alpha gene rearrangements proceed. Endogenous TCR alpha paired
      with transgenic TCR beta could bind to class I or class II molecules, enhance
      positive selection and thereby production of CD4+ or CD8+ cells. Most of the
      'mismatched' CD8+ cells are lambda 2(315)-specific and I-Ed class II restricted,
      and may function as idiotype-specific suppressors of B cells. These results may
      help explain the origin of dual TCR alpha T cells. Furthermore, the authors
      suggest that T cells 'mismatched' for co-receptor/TCR MHC-specificity may be
      enriched among dual TCR alpha T cells.

PMID- 8552990
TI  - Human intestinal B-cell blasts and plasma cells express the mucosal homing
      receptor integrin alpha 4 beta 7.
AB  - Interactions between homing receptors on circulating leucocytes and endothelial
      addressins regulate tissue-specific cellular extravasation. Although integrin
      alpha 4 beta 7 appears to be the main receptor for gut-homing T lymphocytes, less
      is known about molecules mediating mucosal B cell homing. Expression of integrin
      alpha 4 beta 7 on B lymphocytes, B cell blasts, and plasma cells in human gut
      associated lymphoid tissue (GALT; the Peyer's patches and appendix) and lamina
      propria was studied by multi-colour immunofluorescence applied on cryosections.
      Isolated mononuclear cells from the same tissue compartments were examined by
      flow cytometry and compared with peripheral blood B cells. Integrin alpha 4 beta
      7 was expressed by IgA+ B cell blasts and plasma cells (CD38high) in the lamina
      propria, B cell blasts in GALT, and sIgD+ B lymphocytes in peripheral blood. In
      contrast, GALT sIgD+ B lymphocytes were negative or only weakly positive for
      alpha 4 beta 7. These results suggested that B lymphocytes down-regulate alpha 4
      beta 7 upon extravasation in GALT but up-regulate this integrin after antigen
      priming. Thus, alpha 4 beta 7 may be a homing receptor also for B cell blasts
      extravasating in the gut lamina propria, where this integrin is maintained on
      plasma cells, perhaps as a local retention factor.

PMID- 8552991
TI  - In vitro stimulation with glutamic acid decarboxylase (GAD65) leads to an
      oligoclonal response of peripheral T-cells in an IDDM patient.
AB  - The enzyme glutamic acid decarboxylase (GAD65) is a major autoantigen in insulin
      dependent diabetes mellitus (IDDM). To study T-cell reactivity towards GAD,
      peripheral blood leucocytes from seven patients with IDDM and five control
      subjects were stimulated in vitro with recombinant GAD. All diabetics studied
      were heterozygous for diabetes-associated HLA alleles, i.e. HLA-DRB1*03,*04-DQB1
      *0302,*0201. A single IDDM subject (no. GAD65.05) revealed a strong response
      against GAD65. After stimulation, his T-cell receptor beta (TCRBV) usage was
      found to be oligoclonal. The sequence analysis of the putative peptide binding
      region of the T-cell receptor (CDR3 region) of 37 GAD-reactive T-cell clones
      revealed no common CDR3 motif. The stimulation of GAD-reactive T-cells could be
      inhibited with anti-class II monoclonal antibodies, indicating a class II
      restricted T-cell response. In addition, GAD65-responsive T-cells revealed a Th1
      cytokine response pattern. The author's data suggest that GAD-reactive T-cells of
      Th1 phenotype can be obtained after in vitro stimulation of peripheral blood
      leucocytes from an HLA-DRB1*03/*04 heterozygous IDDM patient. The lack of a
      common CDR3 motif suggests the absence of an immunodominant T-cell epitope in
      that patient, or may indicate receptor repertoire spreading of peripheral T
      lymphocytes.

PMID- 8552992
TI  - C3 is activated in hereditary angioedema, and C1/C1-inhibitor complexes rise
      during physical stress in untreated patients.
AB  - Seven patients with hereditary angioedema (HAE) were studied to understand
      further how physical exercise may induce attacks. The most pronounced differences
      between patients and controls, however, were independent of the controlled
      bicycle run (mean values in patients/ controls); C4(g/L): 0.12/0.28 (P = 0.0122);
      C4bc (AU/ml): 137.0/18.0 (P = 0.0002); C4d (mg/mL): 5.03/2.35 (P = 0.0004); C3bc
      (AU/ml): 8.4/6.3 (P = 0.0049); C3a (AU/ml): 11.1/5.6 (P = 0.0102). The ratio C4bc
      to C4 was 1141 versus 64. Consequently, a substantial part of the low amount of
      C4 left in HAE patients consists of activation products, and the authors show for
      the first time that a mild but significant activation of C3 occurs in HAE. The
      two HAE patients treated with danazol had values of C1-INH function and antigen,
      C4, and C2 in-between those of normal and untreated patients, and lower levels of
      split products from C4 and high molecular weight kininogen than untreated
      patients. As a result of the exercise, fibrinolysis increased significantly in
      both patients and controls, while C1/C1-INH complexes rose significantly only in
      the five HAE patients without treatment when compared to the seven controls (P =
      0.0089). This study thus suggests that complement activation is enhanced in
      untreated HAE patients following physical stress.

PMID- 8552993
TI  - Tenidap, but not nonsteroidal anti-inflammatory drugs, inhibits T-cell
      proliferation and cytokine induction.
AB  - T-lymphocytes are involved in the inflammatory response that occurs in affected
      joints of patients with rheumatoid arthritis (RA). Some second-line disease
      modifying anti-rheumatic drugs used in the treatment of patients with RA are
      known to block T-cell activation. The present study assessed whether tenidap, an
      investigational anti-rheumatic drug, affects in vitro T-cell responses such as
      proliferation and cytokine production. It was found that tenidap, in contrast to
      several nonsteroidal anti-inflammatory drugs, inhibits anti-CD3 or IL-2 driven
      proliferative responses of cloned human T-cells. Furthermore, tenidap was found
      to inhibit IFN-gamma production as well as the induction of mRNA encoding IFN
      gamma or TNF-alpha. The results indicate that tenidap may exert at least part of
      its anti-inflammatory activity via inhibition of T-cell function and cytokine
      production.

PMID- 8552994
TI  - Lyme neuroborreliosis: evidence for persistent up-regulation of Borrelia
      burgdorferi-reactive cells secreting interferon-gamma.
AB  - The T-cell response to the aetiologic pathogen Borrelia (B.) burgdorferi in
      patients with Lyme neuroborreliosis (LN) and in control patients with other
      neurological diseases was examined by enumerating B. burgdorferi-reactive T cells
      secreting interferon-gamma (IFN-gamma) with an ELIspot assay. LN patients had
      elevated numbers of B. burgdorferi-reactive IFN-gamma secreting cells in blood
      and approximately 20-fold enriched in the cerebrospinal fluid (CSF). A positive
      correlation existed in CSF between B. burgdorferi-reactive IFN-gamma secreting
      cells and B cells secreting anti-B. burgdorferi IgG antibodies. The up-regulation
      of antigen-specific IFN-gamma secreting cells persisted in peripheral blood up to
      at least 9 months and in the CSF for at least 4 months after termination of
      treatment with antibiotics, when the patients were mostly free from clinical
      signs and symptoms due to LN. How IFN-gamma interplays with other cytokines and
      influences the pathogenesis of LN remains to be studied.

PMID- 8552995
TI  - Lipopolysaccharide effectively up-regulates B7-1 (CD80) expression and
      costimulatory function of human monocytes.
AB  - The influence of lipopolysaccharide (LPS) and various cytokines on the expression
      of the costimulatory molecule B7-1 and intercellular adhesion molecule-1 (ICAM
      1), lymphocyte function associated antigen-3 (LFA-3) and human histocompatibility
      leucocyte antigen-DR (HLA-DR) on human monocytes and their effect on the
      costimulatory function was investigated. Freshly isolated human monocytes
      constitutively express ICAM-1, LFA-3 and HLA-DR, but no B7-1. B7-1 expression was
      up-regulated by LPS and, to a lesser extent, by interferon-gamma (IFN-gamma). The
      other stimuli tested, including IFN-alpha, granulocyte-macrophage colony
      stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha) and GM
      CSF+TNF-alpha, did not influence expression of B7-1 on monocytes. ICAM-1 and HLA
      DR were up-regulated by IFN-gamma and LPS; LFA-3 expression was not influenced.
      LPS also effectively enhanced costimulatory function of monocytes as determined
      in the tetanustoxoid (TT) assay. Blocking of B7 by CTLA-4Ig inhibited the LPS
      induced enhancement of costimulatory function almost completely. Our results
      indicate that the LPS-mediated up-regulation of the costimulatory function of
      human monocytes is mediated by B7. This mechanism may be important for host
      defence against Gram-negative bacteria.

PMID- 8552996
TI  - Ethics in research.

PMID- 8552997
TI  - Ethical aspects of prevention.
AB  - Within the very large area of ethical concerns, the following issues are
      considered in this paper: (i) intellectual and career-oriented ambition, combined
      with the pressure that the competition for funds exerts, may push certain
      scientists to make dubious compromises with their conscience; (ii) exaggerated
      priority is sometimes given to the smooth running of a trial, even at the cost of
      ignoring some ethical requirements; (iii) it is questionable whether preventive
      intervention can adequately and systematically replace primary prevention based
      on the cessation of exposure to carcinogens; (iv) it is of the utmost importance
      to ensure that preventive treatment that is to be administered for long periods
      has no adverse effects or that the benefits by far outweigh the possible risks;
      (v) the informed consent of participants to the trials is essential and it should
      be obtained on the basis of correct, complete and clear information; (vi) a
      different type of informed consent is that of all citizens with regard to risks
      to which they may be exposed voluntarily or involuntarily; (vii) there is no
      justification for, and it is profoundly unethical to omit, delay, or hide
      information that may be relevant to the protection of health. Four examples were
      chosen to illustrate the preceding points.

PMID- 8552998
TI  - Cancer risk for European asphalt workers.
AB  - OBJECTIVES: The feasibility of a European epidemiologic study of cancer risk
      among asphalt workers was examined in Western Europe. The study was motivated by
      occupational and public health concern about possible health risk from exposure
      to bitumen fumes. METHODS: Information on the accessibility and quality of
      epidemiologic resources, retrospective worker records, mortality and cancer
      incidence records, and exposures was requested from research institutes and road
      paving and asphalt mixing companies in 15 European countries. RESULTS: Research
      institutes and asphalt companies in 12 countries responded. It was found that at
      least 44 companies in seven countries can be included in a retrospective
      mortality study of a minimum of 32,000 employees with 356,000 person-years (over
      100 lung cancers). Coal tar will be an important confounder for these data. The
      power of a cohort study of workers who have never worked with tar-containing
      materials remains insufficient. Even in an ambispective study extending to the
      year 2005, the expected lung cancer deaths in a tar-free cohort would be only
      four. CONCLUSIONS: The results suggest that a case-referent study of lung cancer,
      nested in an international cohort of asphalt workers, represents the design of
      choice, conditionally on the possibility of assessing relevant individual life
      time exposures. A cross-sectional determination of relevant biomarkers of
      exposure such as adducts in lymphocytes or the presence of metabolites of
      polycyclic aromatic compounds in urine in a group of workers exposed to bitumen
      fumes will provide further relevant information.

PMID- 8552999
TI  - Occupational and environmental mesotheliomas due to crocidolite mining activities
      in Wittenoom, Western Australia.
AB  - OBJECTIVES: The aim of the study was to review existing cases, calculate rates,
      and predict future numbers of occupational and environmental mesotheliomas from
      Wittenoom. METHODS: On the basis of information contained in occupational and
      environmental histories, Wittenoom cases were extracted from national records
      collected since 1979. Occupational and residential population estimates were
      obtained from company and government records. The proportional latency method was
      used to predict the numbers of mesotheliomas prior to and after the data
      collection phase. Airborne fiber monitoring was used to calculate risk due to
      current levels of contamination in the mine and town environments. RESULTS:
      During 1979-1994, Wittenoom cases (N = 176) comprised approximately 6% of the
      mesothelioma cases recorded in Australia. Of these 122 were employed directly in
      the mining and milling activities, another 18 were involved in the transport of
      raw fiber or tailings, and 34 were town residents or visitors. Due to past
      exposures, additional occupational (N = 301) and environmental (N = 83) cases can
      be expected. Dependent on residential time, existing levels of contamination may
      result in a risk of between < 1 to 57 per million of the population. CONCLUSIONS:
      Latency effects will result in considerable numbers of mesotheliomas appearing
      over the next 10-20 years in Wittenoom. The cessation of mining activities and
      major clean up of the town will result in reduced mesothelioma cases.

PMID- 8553000
TI  - Performance of odds ratios obtained with a job-exposure matrix and individual
      exposure assessment with special reference to misclassification errors.
AB  - OBJECTIVES: Individual assessment of exposure by experts and the use of a job
      exposure matrix are the two main methods of evaluating past occupational
      exposures in community-based case-referent studies. The objective of this study
      was to compare the performance of the estimations of the odds ratio in the two
      methods. This paper focuses on job-exposure matrices whose entries consist of
      proportions of persons exposed. METHODS: Simulations were used to compare the
      variances of the estimations of the odds ratios obtained with the two methods and
      to study the consequences with respect to bias and the precision of the odds
      ratios estimated for misclassifications of exposure produced by either the
      experts or the matrix. RESULTS: When there was no misclassification, the results
      showed that the precision obtained with the job-exposure matrix was about three
      times less than that achieved by experts in a large range of practical
      situations. However, when potential errors of exposure assessment were taken into
      account, the simulations suggested that the test of the hypothesis OR = 1 against
      the alternative OR not equal to 1 when exposure was assessed with an unbiased job
      exposure matrix had a statistical power close to that obtained when exposure was
      assessed by an expert with high sensibility and specificity. CONCLUSIONS: The
      evaluation of exposure with an unbiased job-exposure matrix in studies of the
      association between exposure and disease had a statistical power close to that
      expected in practice with a good expert in the large range of practical
      situations which were investigated.

PMID- 8553001
TI  - Male-mediated risk of spontaneous abortion with reference to stainless steel
      welding.
AB  - OBJECTIVES: It was hypothesized that the welding of stainless steel involves a
      risk of male-mediated developmental toxicity because of exposure to mutagenic
      substances, including hexavalent chromium. The purpose of the present study was
      to corroborate or refute earlier findings that spouses of stainless steel welders
      have an increased risk of spontaneous abortion. METHODS: The occurrence of
      spontaneous abortion among 2520 pregnancies of spouses of 1715 married metal
      workers from 1977 through 1987 was examined. Occupational histories were
      collected with a postal questionnaire in a previous study. Information on
      children born live, spontaneous abortion, and induced abortion was obtained from
      national medical registers. RESULTS: The proportion of spontaneous abortions was
      not increased for pregnancies at risk from stainless steel welding when compared
      with pregnancies not at risk (odds ratio 0.78, 95% confidence interval 0.55-1.1).
      The risk estimate was robust to adjustment for potential confounding effects of
      maternal age and parity and male smoking and alcohol consumption. CONCLUSIONS:
      This study does not corroborate earlier findings that spouses of stainless steel
      welders have increased risk of spontaneous abortion. A reanalysis indicated that
      earlier findings were probably biased because the job exposure of male metal
      workers is apparently modified by the outcome of their partners' first pregnancy.

PMID- 8553002
TI  - Perinatal outcome among the offspring of employees and people living around a
      Swedish smelter.
AB  - OBJECTIVE: The purpose of this study was to determine if emissions from a smelter
      affect the birthweight of offspring and increase the risk of prenatal death.
      METHODS: A historical cohort was formed from registers of birth and employees
      from 1961 to 1991. Comparisons of birthweight and perinatal deaths between
      children born to smelter employees or children born to women living around the
      smelter and those of a reference population were performed. To study reproductive
      effects before 1961, a case-referent study was performed with cases of
      stillbirths from 1937-1961 in one parish. RESULTS: No differences in birthweight
      were found between the children born to employees or to people living near the
      smelter and those in the reference group. An increased risk of perinatal death
      among children born to women in the exposed group was seen during the period 1966
      1970. However, for the rest of the observation period, 1961-1990, this higher
      risk was not apparent. CONCLUSIONS: For the last 20 years emissions from the
      smelter had not affected the birthweight and the risk of perinatal death among
      the offspring of parents living near the smelter or those employed at the
      smelter.

PMID- 8553003
TI  - Frequency of sister chromatid exchange and hematological effects in pesticide
      exposed greenhouse sprayers.
AB  - OBJECTIVES: A cross-sectional study was conducted to investigate whether exposure
      to pesticides in greenhouses causes hemato- or genotoxic damage in sprayers.
      METHODS: The frequency of sister chromatid exchange (SCE) in cultured lymphocytes
      and the number of blood erythrocytes, leucocytes, and thrombocytes were studied
      among 134 greenhouse sprayers exposed to a complex mixture of almost 50
      insecticides, fungicides, and growth regulators and among 157 referents. RESULTS:
      The hematological profiles did not differ between the exposed and unexposed
      groups. The SCE frequency was elevated in nonsmoking, but not in currently
      smoking sprayers when compared with the referents. There was a slight tendency
      towards an increased SCE frequency with decreasing degree of protection during
      pesticide applications. The frequency of pesticide applications, lifetime
      pesticide exposure, and in-season plasma-cholinesterase inhibition (as an
      estimate of current exposure to organophosphates and carbamates) did not
      influence the SCE frequency or any of the hematological parameters. CONCLUSIONS:
      The present results suggest a genotoxic effect from combined subtoxic
      occupational pesticide exposure, whereas no hematogenic effects could be observed
      at the current exposure level.

PMID- 8553004
TI  - Scleroderma and occupational exposure.
AB  - OBJECTIVES: A case-referent study was conducted in the province of Trento, Italy,
      to investigate the possible association between occupational exposure and
      scleroderma (systemic and localized variants). METHODS: Twenty-one cases of
      scleroderma were ascertained from the computerized admission files of all of the
      local hospitals from 1976 to 1991. For each case, two age- and gender-matched
      referents were selected that were discharged from the hospital on the same day as
      the case. The subjects were interviewed with a structured questionnaire which
      included items for personal, work, and medical history. Exposure to organic
      solvents, other selected chemicals, silica dust, and hand-arm vibration was
      carefully investigated. RESULTS: A significant association was found between
      exposure to organic solvents (aromatic hydrocarbons) and scleroderma [odds ratio
      (OR) 9.28, 95% confidence interval (95% CI) 1.08-243.8]. For the men, the OR for
      exposure to silica was 5.20 (95% CI 0.48-74.1), whereas for the women it was 2.11
      (95% CI 0.20-22.0) for exposure to other selected chemicals. CONCLUSIONS: The
      results of this case-referent study are consistent with those of previous case
      reports on the important role of occupation in the etiology of scleroderma. In
      particular, our findings confirm that exposure to organic solvents and silica is
      associated with this rare connective tissue disease.

PMID- 8553005
TI  - Primary liver cancer and renal cell carcinoma in laundry and dry-cleaning workers
      in Denmark.
AB  - OBJECTIVES: Previous studies have shown an excess risk of primary liver cancer
      among women working in laundries and dry-cleaning shops in Denmark at the time of
      the census in 1970. During the period 1970-1987, 14 cases of primary liver cancer
      were observed (standardized mortality ratio 2.7, 95% confidence interval 1.5
      4.5). A nested case-referent study was undertaken in order to classify laundry
      workers and dry-cleaning workers separately. According to hints in the
      literature, renal-cell carcinomas were also included in this analysis. METHODS:
      Original census forms from 1970 were retrieved from the Danish National Record
      Office for the 17 cases with primary liver cancer and the 16 cases with renal
      cell carcinoma and five matched referents per case. RESULTS: All of the 17
      patients with primary liver cancer worked in laundries in 1970, whereas only 74%
      of the referents worked in laundries. Neither was the risk of renal-cell
      carcinoma associated with dry-cleaning work (relative risk 0.7, 95% CI 0.2-2.6).
      CONCLUSIONS: The excess risk of primary liver cancer observed for women working
      in laundries and dry-cleaning shops in Denmark is not likely to be explained by
      exposure to dry-cleaning solvents. Excessive alcohol consumption is not a likely
      explanation either, and the excess risk therefore remains unexplained.

PMID- 8553006
TI  - Lead intoxication caused by skeletal disease.
AB  - BACKGROUND: Inorganic lead is accumulated in the skeleton, which harbors more
      than 90% of the body burden of lead. If rapidly mobilized, this pool may
      constitute a health risk. However, clear evidence of this theory has been
      lacking. HISTORY: A previously healthy 36-year-old Swedish man with more than 10
      years of work-related lead exposure developed headache, musculoskeletal pain, and
      paresthesia of both arms. Two months after the cessation of exposure, the lead
      level in his blood (B-Pb) was 5.5 mumol.l-1, and treatment with chelating agents
      was started. Shortly after the treatment period, he had an accident causing a
      fracture of the right collum femoris. The B-Pb was fairly stable around 1.5
      mumol.l-1 for about two years after the end of exposure (95th percentile 0.6
      mumol.l-1 for occupationally unexposed Swedish men). The examination showed that
      the patient had high skeletal turnover and clearly reduced bone density, as well
      as signs of tubular dysfunction. He was given the diagnosis idiopathic
      osteoporosis. His moderately raised bone lead concentration (about 20
      micrograms.g wet weight-1; normal level in Sweden 4 micrograms.g-1) can only
      partly explain the raised B-Pb, remaining for years after the cessation of
      exposure. Instead, the main explanation is probably the increased skeletal
      turnover. CONCLUSIONS: A combination of a moderately increased bone lead pool and
      skeletal disease seems to increase the risk for lead poisoning.

PMID- 8553007
TI  - Pleural mesothelioma in oil refinery workers.

PMID- 8553008
TI  - Dry cleaning, some solvents used in dry cleaning and other industrial chemicals.
      IARC meeting, Lyon, 7-14 February 1995.

PMID- 8553009
TI  - Etiology of calcium oxalate nephrolithiasis in rats. I. Can this be a model for
      human stone formation?
AB  - Crystal retention is studied in a rat-model system as a possible mechanism for
      the etiology of human nephrolithiasis. A crystal-inducing diet (CID) of ethylene
      glycol plus NH4Cl in their drinking-water is offered to healthy rats to generate
      intratubular crystals. Subsequently, the fate of retained crystals is
      investigated by allowing the rats a tissue recovery/crystalluria phase for three,
      five and ten days, respectively, on normal drinking water. The process of
      exotubulosis is observed in cortex and medulla of aldehyde-fixed kidneys after
      three days recovery. After five days, crystals are predominantly seen there in
      the interstitium. After ten days, cortex and medulla are virtually free of
      crystals. However, in the papillary regions after five and ten days recovery,
      three types of calcium oxalate monohydrate (COM) crystals are present: (1) free
      in the calycine space, (2) sub-epithelially located surrounded by interstitial
      cells within, and (3) covered by macrophage-like cells, outside the original
      papillary surface. After a CID plus three days recovery, a further thirty-seven
      days extra oxalate challenge with solely 0.3 vol% ethylene glycol induced
      intratubular and interstitial oxalate crystals. In the papillary region, large
      sub-epithelial crystals are seen. However, no crystals are seen in kidneys from
      rats given solely (0.5 or 0.8 vol.%) ethylene glycol for thirty days. An oxalate
      re-challenge retards crystal removal.

PMID- 8553010
TI  - Etiology of calcium oxalate nephrolithiasis in rats. II. The role of the papilla
      in stone formation.
AB  - In kidneys of healthy rats submitted to a crystal-inducing diet (CID) with
      ethylene glycol (EG) and NH4Cl, the fate of retained crystals in the papillar
      region is studied during a recovery period of one, five or ten days, as model
      system for human nephrolithiasis. Scanning electron microscopy (SEM) shows, at
      papillary tips bulging into the calycine space, crystal masses covered either by
      the epithelium or a thin fibrous veil, or by unidentified mobile cuboidal cells.
      After CID plus one or five days recovery, small sub-epithelial swellings are seen
      of large sub-epithelial crystals at or around the papillary tip. After CID plus
      ten days, massive sub-surface crystal-containing micrometer-sized stones are seen
      in which the presence of calcium is confirmed by X-ray microanalysis. The
      papillary tip of rats after a re-challenge with an oxalate load from 0.1 vol% EG
      for twelve or forty-two days shows minor lesions. But a re-challenge with 0.3
      vol% EG for thirty-seven days induces large sub-epithelial papillary millimeter
      sized stones. The Von Kossa section staining converts the crystals into a black
      precipitate, but large peri-tubular or peri-vascular calcium deposits are absent.
      A new hypothesis about the etiology of an inductive calcium oxalate monohydrate
      nephrolithiasis is formulated which differs from the one proposed by Randall
      based on his deductive human kidney studies.

PMID- 8553011
TI  - Controlling influence of phosphocitrate in vitro and in vivo on calcium oxalate
      crystal formation and growth.
AB  - Calcium oxalate (CaOx) crystallization in the presence of phosphocitrate (PC) was
      studied by both in vitro and in vivo techniques. Crystals of the monohydrate
      (COM) and the dihydrate (COD) forms were generated under controlled conditions in
      a silica gel matrix. Our data indicated only COD crystals formed when PC was
      present, inferring that the COD to COM transformation was being impeded. COD
      crystals were smaller in size than controls and there was evidence of
      interpenetral twinning. An in vivo study using a rat bladder implant model noted
      similar findings. Scanning electron microscopy (SEM) revealed that implants
      recovered from PC treated rats had primarily COD crystals deposited, whereas both
      the surface and inner layers of encrusted implants from normal rats contained
      predominantly COM crystals. Infrared (IR) analysis confirmed the visual findings
      indicating quantitatively that there was a higher proportion of COD present on
      the implants recovered from the treated rats than in the controls. It is
      concluded that although total CaOx crystallization cannot be eliminated by PC,
      its action could assist in reducing the harmful nature of such crystallites in
      the urine.

PMID- 8553012
TI  - Effect of sodium saccharin on the neonatal rat bladder.
AB  - In a two-generation bioassay, high doses of dietary sodium saccharin (NaSac)
      produce bladder carcinoma in rats, whereas acid saccharin (HSac) does not effect
      the urothelium. NaSac and HSac administered as 5% of the diet to F0 Sprague
      Dawley (SD) and F344 rats, continued through to the weaned male rats for ten
      additional weeks. Control 3H-thymidine labeling index (LI) was high prior to and
      at birth (approximately 11%), declining rapidly by weaning (to < 0.2). Neither
      NaSac nor HSac increased proliferation through 7 days of age. NaSac increased the
      proliferation rate at later times, whereas HSac did not. The LI decreased to
      control levels in NaSac-fed rats switched to control diet after weaning and
      increased in control-fed rats switched to NaSac after birth or weaning. In a
      second experiment, 5% NaSac did not affect urothelial morphology of SD rats
      through 7 days. By 21 days post-birth, urothelial hyperplasia occurred in NaSac
      fed rat. The LI in treated versus control was similar through gestation, with a
      slight difference by 7 days. LI was significantly different by 21 days post
      birth, but was similar between males and females. These results provide
      additional evidence for the increased cell proliferative effects of NaSac during
      the neonatal period, but not during gestation.

PMID- 8553013
TI  - Three-dimensional configuration of crypts of different types of colorectal
      adenomas.
AB  - The three-dimensional configuration of isolated crypts of normal human colonic
      mucosa and colorectal adenomas was examined by scanning electron microscopy. For
      isolation of the crypts, the digestion method with HC1 was used for formalin
      fixed tissues, and the separation method with ethylenediaminetetraacetic acid
      (EDTA) following ultrasonication was applied to fresh tissues. In a comparative
      study, the NaOH cell-maceration method, which visualized the sub-basal laminal
      collagen sheath, was applied. The isolated crypts from the normal colon were
      visualized as a single straight tubule resembling a test tube. Most isolated
      crypts of the tubular adenomas were visualized as elongated fan-like structures
      with several protuberances and a few short branchings. Their average length was
      more than twice that of the normal colonic mucosa crypts. Most crypts of the
      villous adenomas were visualized as slender tubules without protuberances and
      short branchings, and their average length was three times that of the tubular
      adenoma crypts. Most crypts of the tubulovillous adenomas were long and
      triangular with several longitudinal folds and protuberances, and the average
      length was about three times that of the tubular adenoma crypts.

PMID- 8553014
TI  - Scanning electron microscopy and transmission electron microscopy aspects of
      synergistic antitumor activity of vitamin C - vitamin K3 combinations against
      human prostatic carcinoma cells.
AB  - A MTT/formazan assay was used to evaluate the antitumor activity of vitamin C
      (Vit C), vitamin K3 (Vit K3), or vitamin C:vitamin K3 combinations against a
      human prostatic carcinoma cell line (DU145). Both Vit C and Vit K3 alone
      exhibited antitumor activity, but only at elevated doses. When Vit C and Vit K3
      were combined at a C:K3 ratio of 100:1 and administered to the carcinoma cells,
      the 50% cytotoxic concentrations (CD50) of the vitamins decreased 10- to 60-fold.
      Subsequently, the DU145 cells were examined with transmission and scanning
      electron microscopy (TEM and SEM) following a 1 hour treatment with Vit C, Vit
      K3, or Vit C/K3 combined at their 50% cytotoxic dose. Our morphological data
      suggest that vitamin treatment with individual vitamins affects the cytoskeleton,
      the mitochondria, and other membranous components of the cell. Treatment with the
      vitamin combination appears to potentiate the effects of the individual vitamin
      treatment. Specifically, there are abundant necrotic cells. The surviving cells
      display morphological defects characteristic of cell injury.

PMID- 8553015
TI  - Cell surface changes of hemopoietic cells during normal and leukemic
      differentiation: an immuno-scanning electron microscopy study.
AB  - Hemopoietic cells display a wide range of cell surface antigens which are either
      lineage specific or acquired during differentiation. Monoclonal antibodies can be
      used, in conjunction with colloidal gold markers, to identify under the scanning
      electron microscopy (SEM) at the single cell level, specific lineage or
      maturation stages in the hemopoietic bone marrow. Normal bone marrow cells,
      either gradient separated or purified by immuno-magnetic methods and leukemic
      cell samples, which can be considered as "frozen" stages of hemopoietic
      differentiation, have been studied with this method. Typical cell surface
      morphologies, which characterize immature progenitor cells and cells committed or
      differentiated towards the lymphoid, myeloid, erythroid and megakaryocytic
      lineage have been identified. Correlations between cell surface features and some
      hemopoietic cells functions have been attempted on the basis of these findings.

PMID- 8553016
TI  - Ultrastructure of dentin matrix in heritable dentin defects.
AB  - Heritable dentin defects form a group of diseases which exclusively affect dentin
      among the various dental tissues. While one type is associated with the
      generalized connective tissue disorder, osteogenesis imperfecta, other types
      occur as single traits. The clinical manifestations of the dentin defects vary
      from insignificant to severe enough to cause aesthetical and functional failure
      of the teeth. Scanning and transmission electron microscopic studies, reviewed in
      this paper, have markedly clarified the ultrastructure of the aberrant dentin
      matrix. Both similar and different changes seem to occur in the various forms of
      heritable dentin defects. Abnormalities in the appearance and organization
      pattern of collagen fibers in the defective dentin partly resemble those observed
      in skin in generalized connective tissue diseases. The similarity of
      ultrastructural findings in dentin defects, which are currently classified as
      distinct entities, and even in diseases affecting other tissues, could be related
      to the complicated interactions between the extracellular matrix macromolecules.
      Thus, many of the changes observed may be secondary in nature. Ultrastructural
      studies can help us to understand the pathogenesis of the different types of
      heritable dentin defects as well as aid in diagnostics and classification of
      these diseases.

PMID- 8553017
TI  - High resolution electron microscopy of enamel crystallites demineralized by
      initial dental caries.
AB  - Acids produced by various oral bacteria cause mineral loss and crystallite
      dissolution during the development of enamel caries. In order to demonstrate this
      phenomenon, the initial disappearance of lattice fringes and the formation of a
      central perforation in crystallites were examined by high resolution electron
      microscopy (HREM) in initial enamel caries without macroscopic tissue evidence of
      destruction. Ultrathin sections were also examined by selected area electron
      diffraction to reveal the mineral phase of the surface layer in carious enamel. A
      marked variation in the dissolution pattern was disclosed in the initial carious
      lesions. HREM revealed that disappearance of the lattice fringes from the lateral
      portion of the crystallites was predominant in the superficial layer covering the
      lesion, while central perforation of crystallites mainly occurred in the
      subsurface prismatic region. The beginning of the central dissolution occurred at
      the dislocated area where lattice striations appeared to be disordered. Selected
      area electron diffraction of the gradually demineralized enamel revealed a
      pattern consistent with hydroxyapatite (OH-AP) or fluorapatite (F-AP) mineral.
      These findings suggest that the susceptibility to caries of enamel crystallites
      is spatially and temporally different during the progression of the caries.
      Furthermore, the formation of central perforations and the consequent easy
      intracrystalline diffusion of acids might induce rapid crystallite dissolution.

PMID- 8553018
TI  - Comparison of cell sediment and surface grown "test plaque" using scanning
      electron microscopy.
AB  - Scanning electron microscopy was used to compare the morphology, integrity and
      distribution of bacterial cells in a test plaque grown on the surface of enamel
      with that of the cell sediment plaque routinely used in a short-term intraoral
      caries model. Cultures of S. mutans IB-1600 or S. sobrinus 6715-13 were grown in
      complex media supplemented with either 2.0% sucrose (glucan plaque) or 0.2%
      glucose (non-glucan plaque). Cell sediment (CS) plaque was prepared by
      centrifuging the cultures after incubation, recovering the cell sediment, and
      spreading it on Metricel membrane filter paper. Surface grown (SG) plaque was
      prepared by suspending saliva-coated bovine enamel in the culture medium,
      incubating, and recovering the enamel assembly with bacterial accumulations. Cell
      morphology and integrity, as well as the appearance of glucan-like material
      produced by the cells, was similar in both CS and SG test plaques. The cell
      distribution however, varied in the SG plaque from extremes of all cells to all
      glucan, whereas the cell sediment plaque was more uniform in cell distribution. A
      highly standardized test plaque minimizes variability in the intraoral caries
      model. These findings support the contention that the bacterial cells in a cell
      sediment plaque are similar in morphology, integrity and glucan production to
      surface grown plaque, and have the added advantage of uniform distribution, which
      makes the cell sediment plaque more appropriate for intraoral caries model
      studies.

PMID- 8553019
TI  - Early elemental and ionic changes in cultured cells after stimulation with
      epidermal growth factor.
AB  - Stimulation of A431 cells (a human vulval epidermal cell line) with 50 ng/ml of
      epidermal growth factor (EGF) in the presence of 1.7 mM extracellular calcium
      produced a sharp and sustained rise in intracellular ionic Ca2+, increased
      elemental Na, decreased K and a rise in Ca. In the absence of extracellular
      calcium, the initial Ca2+ rise remained but the sustained elevation of
      intracellular Ca2+ was abolished, Na and K fluxes were variable and the Ca did
      not change. Increased Na and decreased K was marked at 2 minutes and returned to
      the control value after 60 minutes. The increase in Ca was an early event. Cells
      stimulated with EGF showed a pronounced morphological disruption, especially the
      mitochondria. The response of NR6/SA3 and NR6/DC7 cells (genetically engineered
      rodent fibroblast cell lines) to EGF stimulation was higher than that of the A431
      cells, as was the resting cytoplasmic Ca2+. Untreated NR6/SA3 and NR6/DC7 cells
      possessed an increased Na/K ratio when compared with A431 cells.

PMID- 8553020
TI  - Gold, electron microscopy, and cancer therapy.
AB  - Radioactive gold has properties suitable for radiotherapy and can provide lethal
      irradiation to cells. If the gold is conjugated to a targeting molecule, such as
      an antibody, it may be possible to specifically deliver the dose to tumor cells.
      Various gold particles are possible candidates and include gold colloids with
      adsorption of antibodies or gold clusters with covalent attachment. Different
      sizes of gold particles are available and some may be preferred for certain
      situations. Problems with intravenous injection and in vivo delivery are
      numerous, and a more tractable application is the direct instillation into the
      urinary bladder of radiogold immunoconjugates to treat superficial bladder
      carcinoma. Preliminary studies indicate the feasibility of this approach.

PMID- 8553021
TI  - The effects of diethyldithiocarbamate (DDC) on the astrocytic cytoskeleton.
AB  - The dithiocarbamates are a group of compounds that are used extensively in
      industry, agriculture and medicine. Exposure to these compounds has caused
      deleterious effects to both the central and peripheral nervous systems. Cultured
      rat hippocampal astroglia treated with 35 micrograms/ml diethyldithiocarbamate
      (DDC) in media were studied for alterations to the cytoskeleton. Examination by
      both immunohistochemistry and scanning electron microscopy revealed disruption of
      the cytoskeletal elements. This occurred in a progressive time-dependent manner.
      Electrophoretic patterns demonstrated two cytoskeletal protein alterations. The
      microtubular protein, beta-tubulin, appeared to have an altered mobility while
      the major intermediate filament protein, glial fibrillary acidic protein (GFAP),
      was decreased. The cytoskeleton appears to be an important cellular target for
      injury by DDC exposure. This study has demonstrated that DDC induces alterations
      in the architecture of the cytoskeleton of astroglia and suggests that these
      changes involve microtubular and intermediate filament proteins.

PMID- 8553022
TI  - Semiquantitative analysis by scanning electron microscopy of cochlear hair cell
      damage by ototoxic drugs.
AB  - The ototoxicity of cisplatin and carboplatin in the organ of Corti of the guinea
      pig was evaluated semiquantitatively. Damage of the stereocilia of outer hair
      cells (OHCs) observed by scanning electron microscopy (SEM) was classified into
      normal, grade 1 (10-50% loss of stereocilia), grade 2 (less than 50% remaining
      stereocilia), or grade 3 (missing stereocilia). The OHCs observed by light
      microscopy (LM) were classified as remaining or missing cells. Fifty OHCs of each
      row in the middle part of each turn of the cochlea were counted (a total of 150
      cells per turn). Guinea pigs were administered 5 mg/kg of cisplatin or 50 mg/kg
      of carboplatin intraperitoneally for three consecutive days. In groups 1 and 2,
      in which both cochlea were fixed in 2.5% glutaraldehyde and 1% osmium tetroxide
      (OsO4) and observed by SEM, the percentages of damage of the OHC stereocilia were
      similar in each cochlear turn bilaterally. In group 3, the right cochleae were
      fixed in OsO4 and observed by phase contrast microscopy as surface preparations.
      Left cochleae were submitted for SEM observation. Missing and grade 3 cells were
      observed at similar percentages in each row of each turn. In group 4, succinate
      dehydrogenase staining was performed in the right cochleae and observed by LM.
      The degree of damage in the right cochleae was compared with that of the left
      cochleae which was observed by SEM. On average, the mean numbers of missing cells
      and cells showing grade 3 damage were similar in each row of each turn. From
      these similarities of evaluation of ototoxicity at LM and SEM levels, it was
      concluded that semiquantitative analysis by SEM only is appropriate for the
      assessment of ototoxicity.

PMID- 8553023
TI  - Scanning electron microscopic observation of dark cells after streptomycin
      perfusion of the vestibule in guinea pigs.
AB  - Hearing has been stabilized in the majority of patients studied in the treatment
      of Meniere's disease with streptomycin. This observation suggests that effects of
      streptomycin may ameliorate endolymphatic hydrops, possibly by attenuating the
      activity of secretory tissue. The purpose of this study is to observe the dark
      cells of the utricle in guinea pigs after streptomycin perfusion of the
      vestibule. Twelve pigmented guinea pigs weighing 250-350 grams were used in this
      study. The vestibules in five guinea pigs were perfused monolaterally with 150
      micrograms of streptomycin in artificial perilymph and, in seven, the vestibules
      were perfused only with artificial perilymph as a control group. Specimens were
      processed for observation with a scanning electron microscope. After streptomycin
      perfusion, the margin of the dark cells became indistinct. The luminal surface of
      the cells bulged out like a dome. The microvilli decreased or were absent, and
      some debris was deposited on the surface. In four of the five animals, the
      luminal membrane of the dark cell ruptured. The cytoplasm and organelle extruded
      into the endolymphatic space. After the cellular debris moved out into the
      endolymph, either a vanished cell or a nucleus in an empty nest was observed.
      These cells appeared damaged and destroyed. The results indicate that the dark
      cells in the membranous wall of the utricle were affected by streptomycin. The
      results lead to the assumption that streptomycin may reduce the volume of
      endolymph by damaging the dark cells of the utricle.

PMID- 8553024
TI  - Vitamin E deficiency as a model of precocious brain aging: assessment by X-ray
      microanalysis and morphometry.
AB  - Vitamin E (alpha-tocopherol) is a known biological antioxidant able to quench the
      lipid peroxidation chain and to protect the cellular structures (e.g., plasma
      membranes) from the attack of free radicals which are reported to play a primary
      role in aging. To assess whether the absence of alpha-tocopherol from the diet of
      young laboratory animals may be considered a reliable model of precocious brain
      aging, intracellular ionic content of brain cortex pyramidal cells,
      ultrastructural features of synaptic contact zones, synaptic mitochondria and
      perykarial mitochondria positive to the succinic dehydrogenase (SDH)
      histochemical reaction with copper ferrocyanide have been investigated by X-ray
      microanalysis and computer-assisted morphometry in young, adult, old and 11-month
      old vitamin E deficient rats. Our data document significant alterations of
      intracellular ionic content, synaptic contact areas and synaptic and perykarial
      mitochondria in aging. Vitamin E deficiency caused similar alterations in adult
      animals. Taking into account the known role of alpha-tocopherol in protecting the
      cellular membrane structure, we support that the common process underlying the
      changes found in aging and vitamin E deficiency is an excessive deterioration of
      the neuronal membrane.

PMID- 8553025
TI  - Gold coating of respiratory cilia for scanning electron microscopy.
AB  - The optimal thickness of gold coating of cilia for scanning electron microscopy
      was studied using respiratory mucosa obtained from pigs. We tested 8 different
      coating times, from 10 seconds to 4 minutes, which resulted in gold layer
      thicknesses varying from 16 +/- 1 nm to 100 +/- 3 nm. The thickness of the gold
      layer with a coating time of 60 seconds and voltage of 2.5 kV was 43 +/- 5 nm.
      This thickness of gold layer gave good image quality without causing any electric
      charging. With thinner gold films, the amount of electric charging increased.
      When the coating time was longer, the gold layer was thicker but image quality
      did not improve. The thicknesses of the gold layers were measured using
      transmission electron microscopy (TEM).

PMID- 8553026
TI  - "Technical improvements in corrosion casting of small specimens: a study on
      mesonephric tubules and vessels of chicken embryos".

PMID- 8553027
TI  - A new scanning electron microscopy approach to the quantification of bone mineral
      distribution: backscattered electron image grey-levels correlated to calcium K
      alpha-line intensities.
AB  - The introduction of backscattered electron (BSE) imaging in scanning electron
      microscopy (SEM) has led to new possibilities for the evaluation of mineral
      distributions in bone on a microscopic level. The different grey-levels seen in
      the BSE-images can be used as a measure for the local mineral content of bone. In
      order to calibrate these BSE-grey-levels (BSE-GL) and correlate them to mineral
      contents, various attempts, using reference samples with known weighted mean
      atomic number and/or using simulated bone tissues with known hydroxyapatite
      concentrations, have been made. In contrast, a new approach is presented here
      based on measurements of the X-ray intensities of the calcium K alpha-line on
      selected areas of real bone samples; the measured intensities are then related to
      the corresponding BSE-GL. A linear positive correlation between weight percent
      (wt%) calcium and BSE-GL was found. When the BSE-mode is standardized using
      carbon and aluminum as references, the different mineral contents in bone samples
      can be recorded as BSE-GL, calibrated to wt% of calcium or hydroxyapatite (HA),
      respectively. The resulting mineral concentration histograms have a dynamic range
      from 0 to 89 wt% HA and have a binwidth resolution of 0.45 wt% HA. The presented
      modifications of the BSE method strongly enhance its feasibility in the field of
      bone research and its application as a special diagnostic tool for bone diseases.

PMID- 8553028
TI  - Experimental calcium oxalate nephrolithiasis and the formation of human urinary
      stones.
AB  - Calcium oxalate nephrolithiasis in rats requires induction of hyperoxaluria which
      results in increased urinary calcium oxalate supersaturation. As a result of low
      to mild chronic hyperoxaluria, calcium oxalate crystals deposit first in the
      papillary collecting ducts. Crystal deposition in the kidneys is preceded by
      calcium oxalate crystalluria and starts with the retention of aggregated calcium
      oxalate crystals in the renal tubules. Retained crystals move from the tubules to
      the interstitium, and in the process, become anchored to the tubular basement
      membrane. Crystal aggregates present in the superficial peripheral collecting
      ducts of the renal papillae ulcerate through to the papillary surface and grow
      into the stones.

PMID- 8553029
TI  - [Clinical manifestations and course of cytomegalovirus colitis in AIDS patients].
AB  - The clinical findings and course in 10 HIV-positive patients with cytomegalovirus
      (CMV) colitis were analyzed. Homosexuality was the main risk factor for HIV
      infection. All patients had markedly reduced CD4 counts (mean 25 x 10(9)/l).
      Symptoms at presentation were chronic diarrhea, weight loss, fever and abdominal
      pain. One of the patients had an abdominal mass in the ileocecal region due to
      inflammation as the leading symptom. Endoscopically the colitis was more often
      segmental than diffuse. In 2 out of 9 patients who underwent colonoscopy, only
      the right hemicolon was affected. Concurrent intestinal infections with up to 4
      different pathogens were found in 7 patients. 5 patients had chorioretinitis as
      an extraintestinal CMV symptom (2 before, 3 after the occurrence of CMV-colitis).
      In only one patient was there a partial response of CMV-colitis to therapy with
      ganciclovir and foscarnet. Even under therapy CMV colitis was complicated in 2
      patients by perforation and inflammatory stenosis respectively. Both needed
      surgical treatment. Most of the patients died of generalized CMV infection or
      wasting syndrome.

PMID- 8553030
TI  - [Initial clinical results with a novel implantable cardioverter-defibrillator: a
      prospective evaluation in 3 Swiss university hospitals].
AB  - The most important technical improvements of implantable cardioverter
      defibrillators (ICD) of the latest generation comprise more sophisticated
      antitachycardia pacing options, stored intracardiac electrograms and biphasic
      shock capabilities which virtually always allow ICD implantation without
      thoracotomy. The present study summarizes the first clinical experience with
      these new devices. In 37 consecutive symptomatic (near sudden death 17, syncope
      16, pre-syncope 4) patients aged 56 +/- 10 years with refractory ventricular
      arrhythmias (presenting arrhythmia: ventricular fibrillation 14, ventricular
      tachycardia 22, not documented 1), an ICD (Jewel PCD 7219, Medtronic) was
      implanted. Coronary artery disease was present in 21, dilated cardiomyopathy in
      5, valvular heart disease in 2 and various conditions in 8 patients; the mean
      left ventricular ejection fraction was 43 +/- 18%. In 29 patients (78%), the ICD
      was inserted in a pectoral and in 8 (22%) in an abdominal position. A non
      thoracotomy lead (NTL) configuration was successfully implanted in 36/37 patients
      (97%) (purely transvenous systems in 30, in combination with subcutaneous patch
      electrode in 6). Surgical complications comprised one pneumothorax, one
      hemorrhage and one death due to sepsis; during a mean follow-up of 5 +/- 3
      months, another patient died of heart failure and 2 revisions (5.4%) for lead
      problems (1 connector, 1 SQ-patch) became necessary. In 23/37 patients (62%), the
      ICD was activated after 74 +/- 89 days post implant. 22 of these 23 patients
      (96%) received one or more appropriate shocks (9 +/- 22 shocks per patient). The
      actuarial survival was 95% at 6 months. In the present study, an ICD of the
      newest generation was successfully implanted without thoracotomy in > or = 97%
      and with purely transvenous systems in > or = 84%. Compared to older systems,
      this has made the implantation procedure remarkably easier and will most likely
      lead to a further reduction in mortality and morbidity. Despite the relatively
      short follow-up, the high incidence of appropriate ICD utilization underscores
      the high recurrence rate of arrhythmias in this population and suggests that the
      ICD may be very effective in preventing unnecessary rehospitalizations.

PMID- 8553031
TI  - [Exposure to solvents in scleroderma: disseminated circumscribed scleroderma
      (morphea) in a painter exposed to perchloroethylene].
AB  - We report on a 45-year-old painter who developed morphea-like scleroderma. He had
      been exposed to perchlorethylene for one year while operating a metal degreaser;
      the perchlorethylene concentration in the workplace ranged between 10 and 25 ppm.
      Whereas systemic scleroderma has frequently been attributed to solvent exposure
      in the past, this is only the third description of a morphea-like scleroderma
      suspected to be related to occupational contact with organic solvents.

PMID- 8553032
TI  - [Diffuse alopecia as side effect of mesalazine therapy in Crohn's disease].
AB  - Within the scope of the participation at the VI. European Crohn's Disease Study
      we observed under therapy with 4 g/day Mesalazine (Pentasa) a strong diffuse hair
      loss on two female patients which disappeared again after discontinuation of
      therapy. A repeated positive exposure in both patients confirmed the causality.
      One patient had thereafter a recurrence of Crohn's disease so she was given a
      reduced dose of Mesalazine (2 g/d). The hair loss began again but on an
      acceptable level for the patient. Thus, it looks like a dose-dependent side
      effect as it is known in the medical literature. These are so far the first two
      cases of hair loss in connection with Pentasa recorded by the Swiss Drug
      Monitoring Center. In the medical literature there are reports about this side
      effect from all producers known in Switzerland (Asacol, Pentasa, Salofalk), which
      suggests a Mesalazine specific side-effect. Since recently higher doses of
      Mesalazine (2-4 g/d) are used in Crohn's disease, a reversible and probably dose
      dependent hair loss must be expected in 1-2% of these patients.

PMID- 8553033
TI  - [Concerning: Scientific raisins from 125 years SMW (Schweiz Med Wochenschr 1995;
      125: 1697-1701)].

PMID- 8553034
TI  - [Scientific raisins from 125 years SMW (Swiss Medical Weekly). Familial colon
      carcinoma. A pedigree from canton Aargau. 1926].

PMID- 8553035
TI  - [Farewell and departure].

PMID- 8553036
TI  - [The orodental situation of aged patients hospitalized at the Hopital de
      Geriatrie of Geneva].
AB  - The purpose of the present study was to identify the major oral and dental
      problems and treatment needs among 216 patients who had been consecutively
      hospitalized at Hopital de Geriatrie de Geneve. The patients were interviewed and
      examined during the week following their hospitalization. There were 150 women
      (73.6%) and 57 men with a mean age of 84 years. Of these 44.4% were completely
      edentulous. The patients with remaining teeth had on average 11 teeth, of which
      24.1% showed active caries. Active root caries was observed in 54.2% of the
      patients with natural teeth. Of the remaining teeth 27.4% were crowned and three
      quarters of these had poorly adapted margins. Removable dentures were observed in
      81% of the patients. Of the complete dentures 18.5% were poorly adapted and 30.3%
      of the removable partial dentures were unstable. Denture stomatitis was observed
      among 20.5% of the denture wearers. It appears from this study that elderly
      patients have many oral, dental and prosthetic problems and that their treatment
      needs are generally important. In order to improve the situation it seems
      necessary to introduce dental care programs for homebound and institutionalized
      elderly patients.

PMID- 8553037
TI  - [The dental status of schoolchildren from abroad in Canton Zurich 1992 to 1994].
AB  - Between 1992 and 1994 DMF-experience was determined in several hundred
      schoolchildren from the City of Zurich and 16 small communities distributed over
      the whole Canton. Immigrants were distinguished from permanently resident
      children with respect to their length of residence. Children who had arrived
      after the age of 5 or 6 (kindergarten-age) showed higher caries prevalence; e.g.,
      at the age of 12, 2.00 (16 communities) and 3.14 (City of Zurich) as compared to
      1.13 and 1.24 DMFT. Children in special classes for learning German, who had
      arrived from former Yugoslavia the year before, had 3.64 DMFT at the age of 12.
      All the children, whether Swiss nationals or non-citizens, who were integrated
      into the school dental service of the City, had satisfactory treatment levels. In
      contrast, recent immigrants from former Yugoslavia had about half of their
      diseased teeth unfilled and often badly destroyed. Therefore, fortnightly tooth
      brushings were introduced as a first measure to lower caries activity.

PMID- 8553038
TI  - [Mercury release from separated amalgam after the use of different
      disinfectants].
AB  - Set amalgam, annealed for twelve days, was cut with water cooling and sucked into
      eight dental units (Systematica 1062 T), equipped with an amalgam separator
      (Multisystem Type 1). Disinfection of the suction devices was performed with
      seven commonly used disinfectants according to the manufacturer's guidelines.
      Rinsing with water served as a control in the last experimental series. The waste
      water was collected at the beginning of the experiments and after disinfection.
      Repeating the experiments for seven times resulted in 112 specimens that were
      analyzed by atomic absorption spectrophotometry. The use of Green & Clean M2 and
      S & M matic resulted in very low releases of mercury. Disinfection with Alprojet
      D and Alprojet DD M2 was comparable with the control group. The release of
      mercury was significantly increased, if compared to Green & Clean and S & M matic
      (p < or = 0.05). The use of Orotol Ultra, Aseptoclean 2, and Tiutol resulted in
      significantly higher releases of mercury, if compared to all other disinfectants
      (p < or = 0.05). Disinfectants containing oxidizing agents provoke an increasing
      release of mercury, thus accumulating the amounts of mercury in the general
      environment.

PMID- 8553039
TI  - [The diagnosis of bone lesions with conventional x-ray images and with a direct
      digital procedure (RVG). An in-vitro study. RadioVisioGraphy].
AB  - The purpose of this study was to evaluate the possibility to delineate artificial
      osseous lesions with direct digital radiography (DDR) in comparison to
      conventional radiography (Rx). Defined lesions of nine different depths were
      created on ten mandibular segments of pigs. A conventional and a direct digital
      radiography was made of each lesion. 400 pairs of images were evaluated by ten
      dentists on the basis of a 5-point rating scale. The statistical evaluation
      included the interexaminer agreement and ROC-analyses. The mean interexaminer
      agreement was low and not significantly different between the two methods (Rx:
      kappa = 21.87 +/- 5.08; DDR: kappa = 20.25 +/- 3.79; p > 0.05). The ROC-analyses
      showed no significant differences between the two methods for the smallest
      lesions (Rx: 0.72 +/- 0.12; DDR: 0.64 +/- 0.12; p > 0.05). Defects between 0.5 mm
      and 1.0 mm of size were significantly better depicted with conventional
      radiographs (p > 0.05). Lesions from 1.25 to 2.0 mm were statistically not
      significantly different (p > 0.05). The diagnosis of lesions of 1.0 mm diameter
      and less than 1.25 mm depth was better delineated by conventional radiographs
      than by direct digital radiographs. However, proper diagnostic results were only
      achieved in lesions bigger than 2.0 mm. During the time this study was conducted
      many technical improvements were introduced for direct digital equipment with
      higher spatial resolutions. The presented methodology is proposed for the
      examination of the diagnostic properties of new imaging tools in comparison to
      conventional radiography.

PMID- 8553040
TI  - [Resin-bonded bridges. A genuine alternative therapy for private practice or a
      long-term temporary measure?].

PMID- 8553041
TI  - [Crown and laminate preparations. Standard preparations for esthetic ceramic
      crowns and ceramic veneers].

PMID- 8553043
TI  - [A poll conducted in 1994 of dentists].

PMID- 8553042
TI  - [Mechanical and chemical plaque control].

PMID- 8553044
TI  - [The anatomically difficult maxilla--preprosthetic surgery and implantology. The
      working group of maxillofacial surgery of the German Society for Dentistry held
      its 46th congress jointly with the German Society for Implantology from 25 to 27
      May 1995 in Bad Homburg].

PMID- 8553045
TI  - [A reduced life expectancy for dentists?].

PMID- 8553046
TI  - [50 years of the fluoridation of drinking water. A report on the International
      Fluoride Symposium--50 Years of Health, Grand Rapids, USA, 15/16 September 1995].

PMID- 8553047
TI  - [A seminar on office computers: a tool that has become unavoidable. A report on
      the display of office computers of 7 September 1995 in Zurich].

PMID- 8553048
TI  - [HIV infection and AIDS in dentistry. A report on the scientific meeting of 29
      September 1995: continuing education at the Institut de Medecine Dentaire in
      Geneva].

PMID- 8553049
TI  - [100 years of dentistry in Zurich. A report on the celebration on the occasion of
      the centenary of the existence of the Center for Dentistry, Oral Medicine and
      Orthodontics of the University of Zurich (ZZMK) on 28 October 1995].

PMID- 8553050
TI  - Treatment of Aeromonas hydrophila infection in a deep tissue wound.
AB  - We report the case of a young woman who sustained a knee laceration in an
      automobile accident and was subsequently exposed to water. Although properly
      cleansed and closed, her wound became infected and she was initially treated with
      a single-dose parenteral cephalosporin. The infection progressed and cultures
      indicated a polymicrobial infection which included Aeromonas hydrophila.
      Significant tissue damage ensued and a lengthy hospitalization was required.
      Aeromonas, although rarely a cause of infection in otherwise healthy individuals,
      should be suspected in wounds exposed to fresh water.

PMID- 8553052
TI  - Drug misuse as a disease.

PMID- 8553051
TI  - Tobacco use in children--a South Dakota physician's perspective.

PMID- 8553053
TI  - Wild dogs in the Serengeti.

PMID- 8553054
TI  - Resistance to mutagenesis.

PMID- 8553055
TI  - Evidence of early cannibalism.

PMID- 8553056
TI  - Extracellular protein kinases.

PMID- 8553057
TI  - NIH budget trouble for AIDS office?

PMID- 8553058
TI  - AMS adds realism to chemical risk assessment.

PMID- 8553059
TI  - Human genetics. New U.K. committee draws fire.

PMID- 8553060
TI  - Social status sculpts activity of crayfish neurons.

PMID- 8553061
TI  - Choreographing the bacterial cell cycle.

PMID- 8553062
TI  - Life at the top: animals pay the high price of dominance.

PMID- 8553063
TI  - New tumor suppressor found in pancreatic cancer.

PMID- 8553064
TI  - Checkpoints take the next step.

PMID- 8553065
TI  - Cellular microbiology emerging.

PMID- 8553066
TI  - Toward an understanding of the correlates of protective immunity to HIV
      infection.
AB  - Considerable progress has been made recently in understanding the genetic,
      immunologic and virologic factors in human immunodeficiency virus (HIV)-infected
      individuals who either rapidly progress or do not progress to acquired
      immunodeficiency syndrome (AIDS). In addition, detection of HIV-specific immune
      responses in HIV-negative individuals who have been exposed to the virus multiple
      times suggests that natural immune responses to HIV may be protective in rare
      individuals. Understanding the correlates of protective immunity to HIV infection
      is critical to efforts to develop preventive HIV vaccines as well as to determine
      the feasibility of treating HIV infection by boosting immunity to HIV.

PMID- 8553067
TI  - Design of a monomeric 23-residue polypeptide with defined tertiary structure.
AB  - Small proteins or protein domains generally require disulfide bridges or metal
      sites for their stabilization. Here it is shown that the beta beta alpha
      architecture of zinc fingers can be reproduced in a 23-residue polypeptide in the
      absence of metal ions. The sequence was obtained through an iterative design
      process. A key feature of the final design is the incorporation of a type II'
      beta turn to aid in beta-hairpin formation. Nuclear magnetic resonance analysis
      reveals that the alpha helix and beta hairpin are held together by a defined
      hydrophobic core. The availability of this structural template has implications
      for the development of functional polypeptides.

PMID- 8553068
TI  - Assembly of a ribonucleoprotein catalyst by tertiary structure capture.
AB  - CBP2 is an RNA tertiary structure binding protein required for efficient splicing
      of a yeast mitochondrial group I intron. CBP2 must wait for folding of the two
      RNA domains that make up the catalytic core before it can bind. In a subsequent
      step, association of the 5' domain of the RNA is stabilized by additional
      interactions with the protein. Thus, CBP2 functions primarily to capture
      otherwise transient RNA tertiary structures. This simple one-RNA, one-protein
      system has revealed how the kinetic pathway of RNA folding can direct the
      assembly of a specific ribonucleoprotein complex. There are parallels to steps in
      the formation of a much more complex ribonucleoprotein, the 30S ribosomal
      subunit.

PMID- 8553069
TI  - C3d of complement as a molecular adjuvant: bridging innate and acquired immunity.
AB  - An optimal immune response should differentiate between harmful and innocuous
      antigens. Primitive systems of innate immunity, such as the complement system,
      may play a role in this distinction. When activated, the C3 component of
      complement attaches to potential antigens on microorganisms. To determine whether
      this alters acquired immune recognition, mice were immunized with a recombinant
      model antigen, hen egg lysozyme (HEL), fused to murine C3d. HEL bearing two and
      three copies of C3d was 1000- and 10,000-fold more immunogenic, respectively,
      than HEL alone. Thus, C3d is a molecular adjuvant of innate immunity that
      profoundly influences an acquired immune response.

PMID- 8553070
TI  - DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1.
AB  - About 90 percent of human pancreatic carcinomas show allelic loss at chromosome
      18q. To identify candidate tumor suppressor genes on 18q, a panel of pancreatic
      carcinomas were analyzed for convergent sites of homozygous deletion. Twenty-five
      of 84 tumors had homozygous deletions at 18q21.1, a site that excludes DCC (a
      candidate suppressor gene for colorectal cancer) and includes DPC4, a gene
      similar in sequence to a Drosophila melanogaster gene (Mad) implicated in a
      transforming growth factor-beta (TGF-beta)-like signaling pathway. Potentially
      inactivating mutations in DPC4 were identified in six of 27 pancreatic carcinomas
      that did not have homozygous deletions at 18q21.1. These results identify DPC4 as
      a candidate tumor suppressor gene whose inactivation may play a role in
      pancreatic and possibly other human cancers.

PMID- 8553071
TI  - rad-dependent response of the chk1-encoded protein kinase at the DNA damage
      checkpoint.
AB  - Exposure of eukaryotic cells to agents that generate DNA damage results in
      transient arrest of progression through the cell cycle. In fission yeast, the DNA
      damage checkpoint associated with cell cycle arrest before mitosis requires the
      protein kinase p56chk1. DNA damage induced by ultraviolet light, gamma radiation,
      or a DNA-alkylating agent has now been shown to result in phosphorylation of
      p56chk1. This phosphorylation decreased the mobility of p56chk1 on SDS
      polyacrylamide gel electrophoresis and was abolished by a mutation in the p56chk1
      catalytic domain, suggesting that it might represent autophosphorylation.
      Phosphorylation of p56chk1 did not occur when other checkpoint genes were
      inactive. Thus, p56chk1 appears to function downstream of several of the known
      Schizosaccharomyces pombe checkpoint gene products, including that encoded by
      rad3+, a gene with sequence similarity to the ATM gene mutated in patients with
      ataxia telangiectasia. The phosphorylation of p56chk1 provides an assayable
      biochemical response to activation of the DNA damage checkpoint in the G2 phase
      of the cell cycle.

PMID- 8553072
TI  - Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle
      checkpoint pathways.
AB  - Mutants of the Saccharomyces cerevisiae ataxia telangiectasia mutated (ATM)
      homolog MEC1/SAD3/ESR1 were identified that could live only if the RAD53/SAD1
      checkpoint kinase was overproduced. MEC1 and a structurally related gene, TEL1,
      have overlapping functions in response to DNA damage and replication blocks that
      in mutants can be provided by overproduction of RAD53. Both MEC1 and TEL1 were
      found to control phosphorylation of Rad53p in response to DNA damage. These
      results indicate that RAD53 is a signal transducer in the DNA damage and
      replication checkpoint pathways and functions downstream of two members of the
      ATM lipid kinase family. Because several members of this pathway are conserved
      among eukaryotes, it is likely that a RAD53-related kinase will function
      downstream of the human ATM gene product and play an important role in the
      mammalian response to DNA damage.

PMID- 8553073
TI  - Bone morphogenetic protein-1: the type I procollagen C-proteinase.
AB  - Bone morphogenetic proteins (BMPs) are bone-derived factors capable of inducing
      ectopic bone formation. Unlike other BMPs, BMP-1 is not like transforming growth
      factor-beta (TGF-beta), but it is the prototype of a family of putative proteases
      implicated in pattern formation during development in diverse organisms. Although
      some members of this group, such as Drosophila tolloid (TLD), are postulated to
      activate TGF-beta-like proteins, actual substrates are unknown. Procollagen C
      proteinase (PCP) cleaves the COOH-propeptides of procollagens I, II, and III to
      yield the major fibrous components of vertebrate extracellular matrix. Here it is
      shown that BMP-1 and PCP are identical. This demonstration of enzymatic activity
      for a BMP-1/TLD-like protein links an enzyme involved in matrix deposition to
      genes involved in pattern formation.

PMID- 8553074
TI  - Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor
      internalization.
AB  - beta-Arrestins are proteins that bind phosphorylated heterotrimeric GTP-binding
      protein (G protein)-coupled receptors (GPCRs) and contribute to the
      desensitization of GPCRs by uncoupling the signal transduction process.
      Resensitization of GPCR responsiveness involves agonist-mediated receptor
      sequestration. Overexpression of beta-arrestins in human embryonic kidney cells
      rescued the sequestration of beta 2-adrenergic receptor (beta 2AR) mutants
      defective in their ability to sequester, an effect enhanced by simultaneous
      overexpression of beta-adrenergic receptor kinase 1. Wild-type beta 2AR
      sequestration was inhibited by the overexpression of two beta-arrestin mutants.
      These findings suggest that beta-arrestins play an integral role in GPCR
      internalization and thus serve a dual role in the regulation of GPCR function.

PMID- 8553075
TI  - The effect of social experience on serotonergic modulation of the escape circuit
      of crayfish.
AB  - The neuromodulator serotonin has widespread effects in the nervous systems of
      many animals, often influencing aggression and dominance status. In crayfish, the
      effect of serotonin on the neural circuit for tailflip escape behavior was found
      to depend on the animal's social experience. Serotonin reversibly enhanced the
      response to sensory stimuli of the lateral giant (LG) tailflip command neuron in
      socially dominant crayfish, reversibly inhibited it in subordinate animals, and
      persistently enhanced it in socially isolated crayfish. Serotonin receptor
      agonists had opposing effects: A vertebrate serotonin type 1 receptor agonist
      inhibited the LG neurons in dominant and subordinate crayfish and had no effect
      in isolates, whereas a vertebrate serotonin type 2 receptor agonist enhanced the
      LG neurons' responses in all three types of crayfish. The LG neurons appear to
      have at least two populations of serotonin receptors that differ in efficacy in
      dominant, subordinate, and socially isolate crayfish.

PMID- 8553076
TI  - Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy
      model.
AB  - In the kindling model of temporal lobe epilepsy, several physiological indicators
      of inhibition by gamma-aminobutyric acid (GABA) in the hippocampal dentate gyrus
      are consistent with an augmented, rather than a diminished, inhibition. In brain
      slices obtained from epileptic (kindled) rats, the excitatory drive onto
      inhibitory interneurons was increased and was paralleled by a reduction in the
      presynaptic autoinhibition of GABA release. This augmented inhibition was
      sensitive to zinc most likely after a molecular reorganization of GABAA receptor
      subunits. Consequently, during seizures, inhibition by GABA may be diminished by
      the zinc released from aberrantly sprouted mossy fiber terminals of granule
      cells, which are found in many experimental models of epilepsy and in human
      temporal lobe epilepsy.

PMID- 8553077
TI  - Single-agent paclitaxel by 3-hour infusion in the treatment of non-small cell
      lung cancer: links between p53 and K-ras gene status and chemosensitivity.
AB  - Currently available cytotoxic drugs are only moderately active in non-small cell
      lung cancer (NSCLC) and prolong survival only slightly. In two published trials,
      single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was
      reported to have significant activity in NSCLC, with response rates of 21% and
      24%. Treatment-limiting hypersensitivity reactions, however, were noted in a
      phase I trial of paclitaxel given as a 3-hour infusion at doses > or = 190 mg/m2.
      We report the results of a phase II trial of paclitaxel given by 3-hour
      intravenous infusion at 210 mg/m2 every 3 weeks in an outpatient setting. The
      study was conducted simultaneously at three centers and included chemotherapy
      naive patients with unresectable locoregional or metastatic NSCLC. The study
      objectives were to evaluate response rate, the potential link between p53 and K
      ras gene mutations and increased paclitaxel resistance, and toxicity. Sixty-two
      patients were eligible for this study. All patients were premedicated with
      dexamethasone 20 mg given orally or intravenously 12 and 6 hours before
      paclitaxel infusion and cimetidine 300 mg and diphenhydramine 50 mg, both given
      60 minutes prior to initiation of paclitaxel infusion. Of the 62 patients who
      were initially enrolled, 50 (44 men and six women) were evaluable for toxicity at
      interim analysis; 47 of these patients were evaluable for response. Twenty-four
      had squamous cell carcinoma, 20 had adenocarcinoma, and six had undifferentiated
      large cell carcinoma. The median age was 61 years (age range, 36 to 75 years).
      The median Zubrod performance status was 1 (range, 0 to 2). Seventeen (36%)
      patients achieved either partial or complete response. Among 24 patients with
      squamous cell carcinoma, eight (33%; 95% confidence interval, 15% to 61%) had a
      partial response. Seven (41%; 95% confidence interval, 18% to 64%) of 17 patients
      with adenocarcinoma had a partial or complete response. Tissue blocks were
      obtained for analysis of K-ras and p53 gene mutations by means of polymerase
      chain reaction followed by single-strand conformation polymorphism assay. Our
      findings indicate that mutations are associated with a poor clinical course and
      may be prognostic of paclitaxel resistance. Paclitaxel was well tolerated. None
      of the patients experienced allergic reactions. Granulocytopenia was generally
      mild. Therapy was interrupted in only two patients because of the development of
      grade 3 neuropathy. In our experience, paclitaxel is one of the most active
      cytotoxic drugs targeting NSCLC.

PMID- 8553078
TI  - Paclitaxel and simultaneous radiation in the treatment of stage III A/B non-small
      cell lung cancer.
AB  - In a clinical phase II trial, radiotherapy and escalating doses of paclitaxel
      (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) were given concurrently to
      patients with stage IIIA/B non-small cell lung cancer. Radiotherapy was given in
      daily doses of 2 Gy, 5 days a week, in weeks 1 to 3 and 6 to 8 for a total dose
      of 56 Gy. Paclitaxel was given in 3-hour infusions on day 1, also in weeks 1 to 3
      and 6 to 8. The starting dose level was 50 mg/m2; the subsequent dose levels were
      60, 72, 86, and 103 mg/m2. Cohorts of three to six patients were assigned to each
      dose level until intolerable toxicity (eg, World Health Organization grade 3 or 4
      leukopenia) occurred in three of the six patients. Currently, 15 patients have
      entered the study. Twelve patients have finished the treatment protocol and are
      evaluable for toxicity and response. Hematologic toxicity was mild, and even at
      86 mg/m2, the highest evaluable dose level, no severe myelosuppression was
      noticed. The main clinical toxicity was the occurrence of pulmonary infections,
      which were seen in five patients. One of these patients had a Pneumocystis
      carinii infection, but no pathogens were isolated from the four others with
      interstitial infections. Mild to moderate esophagitis was seen in five patients.
      All patients showed a decrease of tumor size. Four patients had a major response
      with nearly complete disappearance of radiologic tumor signs, five patients had a
      partial remission, and three patients experienced a minor response. Thus, the
      overall response rate was 75%. In summary, the maximum tolerated dose of
      paclitaxel has not yet been achieved, the occurrence of pulmonary infections
      represents the major clinical toxicity, and the extremely high response rate
      merits further clinical evaluation of this regimen.

PMID- 8553079
TI  - Single-agent paclitaxel at first relapse following adjuvant chemotherapy for
      breast cancer.
AB  - The efficacy and safety of paclitaxel (Taxol; Bristol-Myers Squibb Company,
      Princeton, NJ) was studied in 27 patients who had relapsed following
      adjuvant/neoadjuvant chemotherapy for breast cancer. Paclitaxel 225 mg/m2 given
      as a 3-hour infusion is an effective regimen in this poor-prognosis population.
      It is well tolerated and can be given in an outpatient setting without routine
      use of granulocyte colony-stimulating factor. It also can be given in repeated
      cycles without excessive dose reductions or delays. An objective response rate of
      54% was obtained. Responses were seen at all disease sites. Future studies must
      explore a paclitaxel-containing combination regimen to improve response rates
      further.

PMID- 8553080
TI  - The role of paclitaxel in the management of coelomic epithelial carcinoma of the
      ovary: a review with emphasis on the Gynecologic Oncology Group experience.
AB  - Coelomic epithelial carcinoma of the ovary, the most common cause of death from
      cancer of the female genital tract in the United States, presents most commonly
      as advanced (stage III or IV) disease. Management consists of aggressive surgical
      cytoreduction followed by combination chemotherapy, until recently, a platinum
      compound plus an alkylating agent. The recent identification of the activity of
      paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) offers the
      potential to improve further the management of patients with advanced disease.
      That this agent might enhance current front-line therapy is supported by its
      unique mechanism of action and by the significant numbers of responses reported
      in patients clinically resistant to the platinum compounds: more than 20% of
      these patients responded to paclitaxel as salvage therapy in four different phase
      II trials. These observations led to a phase I Gynecologic Oncology Group trial
      that showed that paclitaxel 135 mg/m2 over 24 hours followed by cisplatin 75
      mg/m2 could be given every 3 weeks. This group then compared six cycles of the
      identified regimen with six cycles of standard cisplatin/cyclophosphamide
      chemotherapy given every 3 weeks in a phase III trial in 388 previously untreated
      patients with large-volume (residual nodules > 1 cm after surgery) disease. The
      results show the superiority of the paclitaxel/cisplatin regimen: overall
      response rate 77% versus 62%, clinical complete response 54% versus 33%,
      frequency of achieving a grossly disease-free state at second-look laparotomy 40%
      versus 22%, progression-free survival 18 versus 13 months, and overall survival
      38 versus 24 months. Thus, paclitaxel/cisplatin is the new standard of care for
      patients with advanced ovarian carcinoma. Current phase III studies explore
      further the role of paclitaxel in front-line therapy: the relative merits of
      single-agent versus combination chemotherapy, the role of interval surgical
      cytoreduction combined with paclitaxel/cisplatin, the value of carboplatin-based
      versus cisplatin-based combinations with paclitaxel, the significance of the
      paclitaxel infusion length (3 v 24 v 96 hours), and the value of more dose
      intense combinations.

PMID- 8553081
TI  - Pilot study with fixed-dose carboplatin and escalating paclitaxel in advanced
      ovarian cancer.
AB  - A dose-finding study was performed in 27 ovarian cancer patients to define the
      maximum tolerated dose of a 3-hour infusion of paclitaxel (Taxol; Bristol-Myers
      Squibb Company, Princeton, NJ) in combination with a fixed dose of carboplatin.
      The median age of the patients was 55 years (age range, 30 to 74 years), the
      median performance status was 0 (range, 0 to 2), and the sizes of tumors residual
      to first surgery were identified as > or = 1 cm (14 patients) or less than 1 cm
      (13 patients). All patients received carboplatin at a fixed dose of 300 mg/m2
      over 1 hour. Paclitaxel was administered as a 3-hour infusion at five dose
      levels, starting at 150 mg/m2 and increasing in 25 mg/m2 increments to 250 mg/m2.
      In the absence of toxicity, courses were repeated every 4 weeks for a total of
      six cycles. Mild emesis, general alopecia, and moderate myalgias occurred.
      Hypersensitivity and cardiotoxicity were observed in 7.4% and 14.8% of patients,
      respectively. Moderate peripheral neuropathy was experienced by 30% of patients.
      Grade 3 and 4 neutropenia lasted less than 7 days; no patients required
      hospitalization for sepsis or febrile neutropenia, and no supportive treatment
      with granulocyte/granulocyte-macrophage colony-stimulating factor was needed.
      Twenty-one patients were evaluable for response. Overall response rate (complete
      response+partial response) was 81%, and responses were observed at all paclitaxel
      dose levels. The maximum tolerated dose was not achieved. In conclusion, with a
      fixed dose (300 mg/m2) of carboplatin, paclitaxel can be administered by 3-hour
      infusion at 250 mg/m2 with manageable toxicity and no supportive care is needed.

PMID- 8553082
TI  - Clinical phase I study of paclitaxel followed by cisplatin in advanced head and
      neck squamous cell carcinoma.
AB  - We performed a clinical phase I trial of the combination of paclitaxel (Taxol;
      Bristol-Myers Squibb Company, Princeton, NJ) and cisplatin in patients with
      recurrent or metastatic squamous cell carcinoma of the head and neck, using a 3
      hour infusion of paclitaxel followed by a 1-hour infusion of cisplatin. Treatment
      with this combination was repeated every 21 days. Patients who had received prior
      treatment with platinum-containing regimens were excluded. However, patients who
      had received two or fewer courses of radiochemotherapy not including platinum
      compounds were eligible. At present, 21 patients have been entered into this
      ongoing study. Doses ranged from paclitaxel 135 mg/m2 plus cisplatin 75 mg/m2 to
      paclitaxel 250 mg/m2 plus cisplatin 100 mg/m2. The maximum tolerated dose was
      reached at paclitaxel 250 mg/m2 and cisplatin 100 mg/m2. The dose-limiting
      toxicity of this regimen was myelosuppression (leukopenia, granulocytopenia).
      Clinically, neurosensory toxicity was moderate. However, preliminary analyses of
      threshold electrotonus studies indicate the presence of subclinical neurotoxicity
      in most patients. One patient receiving paclitaxel 200 mg/m2 plus cisplatin 100
      mg/m2 developed grade 3 motor neurotoxicity. Profound orthostatic hypotension was
      observed in five patients receiving paclitaxel 200 mg/m2 plus cisplatin 100 mg/m2
      or higher. Neurotoxicity was of delayed onset and slowly reversible, and its
      severity appeared to be dose related. Twelve patients are currently evaluable for
      response. Of these, three partial remissions were observed (6, 6+, and 3+
      months). Five additional patients had stable disease. We conclude that the
      combination of paclitaxel administered as a 3-hour infusion followed by cisplatin
      is an active regimen in advanced head and neck cancer. In addition to
      myelosuppression, orthostatic hypotension may be a potentially significant
      clinical toxicity. Clinical phase II studies have been initiated, using a dose of
      paclitaxel 200 mg/m2 and cisplatin 100 mg/m2.

PMID- 8553083
TI  - Phase I/II study with paclitaxel in combination with weekly high-dose 5
      fluorouracil/folinic acid in the treatment of metastatic breast cancer: an
      interim analysis.
AB  - Phase II study results demonstrating high efficacy and low toxicity for a weekly
      schedule of high-dose 5-fluorouracil/folinic acid (5-FU/FA) in intensively
      pretreated metastatic breast cancer patients prompted the addition of paclitaxel
      (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this regimen in a phase
      I/II trial in outpatients: high-dose 5-FU (24-hour infusion)/FA (2-hour infusion
      preceding 5-FU) is given for 6 weeks (days 1, 8, 15, 22, 29, and 36), with
      paclitaxel (3-hour infusion) administered on days 1 and 22; 2 weeks' rest
      follows. Folinic acid 500 mg/m2 was administered throughout; the respective 5-FU
      doses for dose levels 1 through 3 were 1.5, 1.8, and 2.0 g/m2 with paclitaxel 135
      mg/m2. Dose level 4 (500 mg/m2 FA, 2.0 g/m2 5-FU, and 175 mg/m2 paclitaxel) was
      chosen for phase II evaluation. To date, 46 patients with bidimensionally
      measurable disease (four each at dose levels 1, 2, and 3, and 34 at dose level 4)
      have been entered. The 12 patients treated at dose levels 1 through 3 were
      titrated to level 4 doses when phase II began; 35 patients are evaluable for
      response. The median age is 46 years, and the median number of metastatic sites
      is 2.5. Fourteen patients had received adjuvant chemotherapy, nine chemotherapy
      for metastasis, and 23 chemotherapy both adjuvantly and for metastasis. Of 31
      anthracycline-treated patients, 27 had anthracycline-resistant disease. No dose
      limiting toxicity appeared until dose level 4, when grade 3 or 4 leukopenia and
      diarrhea occurred in 15 and eight, respectively, of 108 cycles. Mild to moderate
      mucositis, hand-foot syndrome, myalgia, and nausea/vomiting occurred in 20% to
      40% of cycles. One (3%) of the 35 patients had a complete response, 18 (51%) had
      partial responses, 14 (40%) had stable disease, and two (6%) had disease
      progression. Eleven (55%) of 20 evaluable patients with anthracycline-resistant
      disease responded (95% confidence interval, 34% to 76%). Median time to maximum
      response was 2 months, and the remission duration was 8+ months. Median survival
      time has not been reached. Paclitaxel and weekly high-dose 5-FU/FA was well
      tolerated and highly effective, even in patients with anthracycline-resistant
      metastatic breast cancer. The regimen can be administered safely to outpatients.

PMID- 8553084
TI  - Essential hypertension: a renal perspective.

PMID- 8553085
TI  - Validating the platelet count.

PMID- 8553086
TI  - The do-not-resuscitate order.

PMID- 8553087
TI  - Comparison of platelet counts in simultaneous venous and capillary blood samples
      using an automated platelet analyser.
AB  - Platelet counts (PC) obtained simultaneously from capillary blood (CB) are
      generally lower than those from venous blood (VB). We quantified this difference
      in 17 patients with low platelet counts (LPC) and 18 healthy volunteers with
      normal platelet counts (NPC). The reproducibility of the counts in these 2 groups
      of subjects was also evaluated. The mean venous platelet count (VPC) and the mean
      capillary platelet count (CPC) were 67 +/- 30 x 10(3)/ul (+/- SD) and 61 +/- 23 x
      10(3)/ul (p = 0.012) in the LPC, and 264 +/- 44 x 10(3)/ul and 234 +/- 45 x
      10(3)/ul (p = 0.00016) in the NPC respectively. The mean difference (d) in the PC
      between VB and CB were 9.4 +/- 13.1 x 10(3)/ul and 19.4 +/- 17.6 x 10(3)/ul in
      the LPC and NPC respectively. The coefficients of variation (CV) of double counts
      for VB and CB were 8.1 +/- 8.3% and 9.8 +/- 8.6% for LPC, and 2.3 +/- 1.6% and
      2.5 +/- 2.2% for NPC respectively. In conclusion, VPC was frequently (82.9% or
      29/35 cases) higher than CPC. In addition, in patients with LPC, the agreement
      between VPC and CPC was poor and the counts were less reproducible.

PMID- 8553089
TI  - Effect of intraperitoneal zinc on the haematological profiles of C57/6J mice.
AB  - Zinc is included in a number of medications and haematotoxic effects due to zinc
      excess have been reported. In this study, the haematological profiles
      (haematocrit, haemoglobin, total white blood cell count, differential white blood
      cell count and platelets) of mice treated with zinc were evaluated.
      Intraperitoneal zinc chloride was administered to C57/6J mice in varying dosages
      from 1.4-14 micrograms/g body weight, four times a week for a period of three
      weeks. Zinc chloride had no effect on the haematological profiles of these mice
      since the blood cell counts of treated mice were not significantly different from
      the controls (p < 0.05), with the exception that at half LD50 of zinc chloride
      (14 micrograms/g body weight) a reactive thrombocytosis resulted. (The platelet
      counts between the control and experimental group of mice were significantly
      different, exceeding 95% confidence limits; p = 0.016). We postulate that the
      specific effect on platelets was due to zinc being a potent inhibitor of phenol
      sulfotransferase (PST), an enzyme which is involved in many metabolic pathways.
      Platelets are a rich source of PST and the thrombocytosis observed was probably a
      compensatory mechanism to raise the levels of PST in the body.

PMID- 8553088
TI  - Do-not-resuscitate orders: towards a policy in Singapore.
AB  - Despite the fact that the pioneers of cardio-pulmonary resuscitation (CPR)
      designed the techniques for victims who were meant to be "salvable", currently
      CPR is largely applied to anyone who collapses, regardless of their underlying
      illness. However, the central fact is that CPR (and all its related complex and
      expensive technology) has a very low success rate (in terms of eventual hospital
      discharge) and the most important determinant of survival has always been the
      nature and stage of the underlying illnesses. All these bespeak of a need to have
      do-not-resuscitate (DNR) orders which will incorporate the pertinent medical,
      ethical, socio-cultural and legal components. In this discussion paper some
      guidelines for DNR orders relevant to Singapore are proposed, the main rationale
      of the guidelines are explained and some challenges and needed changes associated
      with its implementation are addressed.

PMID- 8553090
TI  - Phenomenological differences of delusions between schizophrenic patients of two
      cultures of Malaysia.
AB  - Two hundred and seventy schizophrenia patients were interviewed using the Present
      State Examination to elicit the phenomenological symptoms of the illness.
      Cultural factors and ethnicity were found to be significant variables associated
      with the symptoms. Higher prevalence of religious and other subculturally related
      delusions were common in Kelantan patients. Our general belief that Malaysian
      culture influences symptomatology of mental illness seems to be proven.

PMID- 8553091
TI  - Slow continuous ultrafiltration (SCUF)--the safe and efficient treatment for
      patients with cardiac failure and fluid overload.
AB  - Slow Continuous ultrafiltration (SCUF) was first used in 1980 as an alternative
      mode of fluid removal for patients with oliguric acute renal dysfunction from
      whatever causes. The advantage of this treatment is that haemodynamic parameters
      remain stable in the presence of significant removal of fluid. We are describing
      our experience in 7 patients [age: 57 +/- 9 years; 4 male, 3 female] with cardiac
      failure and fluid overload who had undergone 8 sessions of SCUF. All of them had
      renal impairment and were resistant to diuretics. Blood lines were attached to a
      Kawasumi Renak-E dialyser (Cuprophane membrane) in series using Gambro AK10
      dialysis blood pump. The following parameters were monitored: Blood pump (Qb):
      175 +/- 26 ml/min, time (T): 393 +/- minutes. Venous pressure averaged a55 +/- 24
      mmHg. We achieved ultrafiltration of 2,189 +/- 699 ml/session or 5.5 +/- 1.7
      ml/hr. There was no significant change in blood pressure [systolic pre: 143 +/-
      14, post: 136 +/- 13 mmHg, not significant; diastolic pre: 87 +/- 10, post: 83 +
      10 mmHg, not significant and pulse rate [pre: 87 +/- 9 vs post: 84 +/- 2 per
      minute, not significant. Heparin dosage averaged 274 +/- 26 IU/hr during the
      SCUF. We conclude that SCUF is beneficial to diuretic resistant patients with
      cardiac failure and fluid overload in whom dialysis treatment is not required.

PMID- 8553092
TI  - Acute renal failure in a teaching hospital.
AB  - This was a retrospective study of the clinical course of 164 adult inpatients
      with acute renal failure (ARF) at the Hospital of the University of Science
      Malaysia admitted from June 1986 to May 1990. The mean age was 49.8 +/- 17.2
      years. 33.5%, 54.9% and 11.6% were surgical, medical and obstetrical patients
      respectively. Obstructive uropathy, poor cardiac output or decrease in
      intravascular volume and infection accounted for more than 67% of the cases.
      Acute renal failure was present at admission in 113 (69%) patients. The majority
      of the patients (80%) had nonoliguric acute renal failure with daily output of
      urine of more than 400 ml. Compared with nonoliguric patients, oliguric patients
      had higher mortality (56.3% vs 18.9%, p < 0.01), and needed dialysis more
      frequently (43.8% vs 12.9%, p < 0.01). Early recognition of acute renal failure,
      improvement in early treatment of renal stones and discerning use of nephrotoxic
      drugs could result in decrease in incidence and severity of renal failure.

PMID- 8553093
TI  - Characterisation of Campylobacters from Malaysia.
AB  - Eight-five clinical and 15 poultry isolates of Campylobacter species were
      characterised by biotyping, serotyping and by using a radiolabelled DNA probe. A
      total of 80% of the isolates from both sources were identified as C. jejuni. Also
      amongst the clinical strains were 5 c. jejuni subsp. doylei, 7 C. coli, 3 C. lari
      and 8 were untypable. The similarity in the distribution of C. jejuni in the
      clinical and poultry isolates adds credibility to published reports of chickens
      being the most common source of Campylobacter infections. Although the gold
      standard for identification of C. jejuni is the DNA probe, serotyping is more
      discriminating while biotyping is the most feasible method in most laboratories.

PMID- 8553094
TI  - Poisoning due to common household products.
AB  - From 1988 to 1992, 187 patients were admitted in four general medical wards at
      the Prince of Wales Hospital, Hong Kong with poisoning due to common household
      products. The main agents involved included "Dettol" liquid (46%), cleaning
      products (19%), pesticides (14%), and shampoos (10%). The majority of patients
      had only relatively mild symptoms. Ingestion of Dettol liquid and strong
      corrosives tended to be associated with serious complications and deaths. Two
      patients died after aspiration of Dettol liquid and detergent before and/or
      during gastric lavage. One other patient died after swallowing sulphuric acid. As
      with all poisoning, it is very important that the airway is adequately protected
      before gastric lavage is performed.

PMID- 8553095
TI  - Reference ranges for lymphocyte subsets in a defined Malaysian population.
AB  - The aim of this study was to establish the lymphocyte subset reference ranges in
      a defined Malaysian population as well as to determine inter-racial differences
      for these values. Normal blood obtained from 152 subjects (55.9% Malay, 26.3%
      Chinese and 17.7% Indian) was immunophenotyped. Results obtained (expressed as
      mean +/- SD %), absolute count (x 10(6) cells/mm3) were as follows: CD3:66.5 +/-
      8.6%, 2,066; CD4:33.2 +/- 8.5%, 1,028; CD831.6 +/- 8.9%, 982; CD19:12.0 +/- 0%,
      5,374, and CD56+CD16:20.9 +/- 9%, 1,638. There were no significant differences
      between the percent lymphocyte subsets of the three racial groups. However, the
      absolute number of CD4 cells and CD19 cells in Chinese was significantly lower (p
      < 0.05) compared to the Indian and the Indian and Malay groups respectively.
      Comparison of our results with other reports showed that the percentage of
      Natural Killer cells in this population is higher than that reported for
      Caucasian population.

PMID- 8553096
TI  - Unusual manifestations of Mycoplasma pneumoniae infection in children.
AB  - Mycoplasma pneumoniae infection is no longer a benign condition it was originally
      thought to be. Many extrapulmonary manifestations affecting major organ systems
      like the central nervous system, cardiovascular system, haematological system,
      gastrointestinal system, musculoskeletal system and renal system have been
      described. Early recognition of these manifestations is often difficult and
      serological diagnosis may not be helpful. Three patients with large pleural
      effusions, encephalitis, hemiplegia, hepatitis, autoimmune haemolytic anaemia and
      renal failure are discussed to highlight the many varied presentations associated
      with this infection.

PMID- 8553097
TI  - Serodiagnosis of melioidosis in Malaysia.
AB  - Current diagnosis of melioidosis is based on bacterial culture and/or serology
      which is becoming increasingly useful. An IgM-ELISA using heat-killed whole cells
      of Pseudomonas pseudomallei was developed and compared with an indirect
      haemagglutination technique (IHAT) and an indirect immunofluorescent
      technique(IFAT). The IgM-ELISA using a P:N ratio of > or = 2 had a sensitivity of
      91% and a specificity of 96%. All 3 assays were further used in a
      seroepidemiological survey amongst different groups of patients and healthy
      individuals. It was found that the IFAT performed better than the IHAT, detecting
      antibodies to P. pseudomallei in 6% of diabetics, 5% of pyrexics, 8% of pregnant
      women and 3% of farmers. For the same groups the IgM-ELISA detected antibodies in
      1% of pyrexics, 8% of pregnant women and a further 14% of farmers. The IgM-ELISA
      was found to be sensitive and useful for the serological diagnosis of acute
      melioidosis.

PMID- 8553098
TI  - The association of the amoebic colitis and chronic ulcerative colitis.
AB  - Three patients with idiopathic ulcerative colitis and infection of Entamoeba
      histolytica were reviewed. They represented three different relationships between
      the two conditions, vis asymptomatic carrier, coexisting infection and
      superinfection causing exacerbation of colitis. A two-way relationship between
      amoebic colitis and ulcerative colitis has been discussed and the possible
      mechanisms in the literature have been reviewed. In patients with a short history
      of diarrhoea and in tropical countries where amoebic infection is endemic, it is
      important to role out amoebic colitis before commencing steroid therapy for
      inflammatory disease.

PMID- 8553099
TI  - Colorectal cancer in the young adult.
AB  - Out of 964 patients presenting with primary colorectal cancer (CRC) to the
      Department of Colorectal Surgery, Singapore General Hospital between April 1989
      until December 1992, there were 57 (5.9%) aged 40 years or less. These younger
      patients were significantly more likely to have a family history of cancer,
      particularly CRC; a tumour situated more proximally; and tumours displaying
      certain characteristics histopathologic features. There were no adverse findings
      for clinicopathologic staging at presentation, curative resection rate, and
      systemic recurrence rate within the early follow up period. With proper
      management, the young adult with CRC enjoys the same outlook as his older
      counterpart. But, in view of the likely operation of inherited genetic factors,
      follow up surveillance of the patient and the provision of advice and screening
      are vital elements in optimising outcome. Furthermore, advice and screening
      should be available for first degree relatives as well.

PMID- 8553100
TI  - Oesophageal motility disorders: rapid functional diagnosis using computerised
      radionuclide oesophageal transit study.
AB  - Ten patients presenting with central chest pain and/or dysphagia were diagnosed
      to have oesophageal motility disorders (OMD) with an incoordinate motor function
      using computerised radionuclide oesophageal transit study (RT). The criteria for
      diagnosis of OMD with incoordination using RT were: an 'incoordinate' or 'to and
      fro' pattern characterised by multiple peaks of activity, prolonged total transit
      time or radionuclide bolus through entire length of oesophagus and a significant
      portion of bolus entering the stomach. These features are characteristic but not
      pathognomonic of diffuse oesophageal spasm (DES) as they are also seen in non
      specific motility disorders (NSMD) and occasionally in order oesophageal motility
      disorders. Mechanical obstruction in the oesophagus and coronary artery disease
      were excluded appropriately in these patients. When manometry is not available,
      RT is a sensitive, safe, simple, rapid and non-invasive alternative modality in
      confirming certain oesophageal motility disorders.

PMID- 8553101
TI  - Urinary tract infections.
AB  - Urinary tract infections are common clinical problems which result in significant
      morbidity and even mortality. UTI's can range from minimal disease to life
      threatening sepsis and it is important to differentiate between the former which
      usually involves the lower urinary tract and the latter which invariably involves
      the upper urinary tract. Diagnosis depends on an abnormal urine microscopy and
      demonstration of bacteria in the urine. Pre-therapy urine cultures are not
      mandatory in young women with uncomplicated UTI and many studies support the
      efficacy of short-course therapy in this groups of patients. For other patients,
      microbiological and radiological investigations are required and there is
      insufficient data to support short course therapy in these patients. Treatment
      guidelines are different in special situations such as prostatitis, pregnancy,
      catheter-related infection and recurrent infections.

PMID- 8553102
TI  - Psychiatric disorders in pre-schoolers.
AB  - The psychiatric disorders seen in preschoolers are reviewed. Behaviour problems
      are the most commonly seen. These may be due to reaction to stress, developmental
      problems of attachment and temperamental characteristics such as shyness and
      aggressiveness. Related to behavioural problems are the developmental disorders
      of enuresis, encopresis and constipation. The rate of behaviour problems in
      Singapore was found to be 7% which compares favourably with studies overseas.
      Disorders that have their onset in the preschool period include Attention Deficit
      Hyperactivity Disorder (ADHD) and Pervasive Developmental Disorders. ADHD is
      increasingly important because of the response to Ritalin and pervasive disorders
      because of the recognition that autistic states probably cover a spectrum of
      disorders. Aetiological factors of preschool psychiatric disorders include
      biological and psychosocial contribution. The latter is associated with the
      quality of the home environment and quality of care experienced by the child.
      Assessment methods include the gathering of developmental data such as the IQ and
      appropriate behavioural checklists. Direct observation is increasingly practised.
      Management methods range from drug therapy (mainly in ADHD), to traditional
      psychodynamic, family and behavioural therapy.

PMID- 8553103
TI  - Clinics in diagnostic imaging (4). Renal angiomyolipoma with spontaneous
      perinephric haemorrhage.
AB  - A 69-year-old Chinese woman presented with acute right-sided abdominal pain.
      Intravenous urogram and ultrasound demonstrated a fatty lower renal pole mass
      with a perinephric collection. The diagnosis of renal angiomyolipoma was
      confirmed by computerised tomography. The perinephric haemorrhage resolved with
      conservative treatment. The classification, clinical features and management of
      this entity is discussed. The role of imaging in diagnosis and follow-up of renal
      angiomyolipoma is emphasised.

PMID- 8553104
TI  - ST elevation in inferior leads--ECG localisation of infarct related artery.

PMID- 8553105
TI  - Dopa-responsive dystonia of childhood: a case report.
AB  - A 5-year-old Chinese boy presented with difficulty in walking and weakness of his
      lower limbs for one year, especially towards the evening. Bilateral equinovarus
      posturing of the feet and tremors of the upper limbs were noted on physical
      examination. Dopa-responsive dystonia was diagnosed after a remarkable
      symptomatic response to levodopa. This disorder is reported here to highlight an
      often misdiagnosed condition is children which is important because it is
      treatable. Dopa-responsive dystonia should be considered in the differential
      diagnosis of gait disturbance in children.

PMID- 8553106
TI  - Left ventricular myxoma, adrenal tumour and cutaneous vasculitis--a case report.
AB  - Cardiac myxoma has myriad presentations including cutaneous vasculitis. It has
      also been associated with endocrine neoplasm in Carney's Complex. We report a
      Chinese patient with cutaneous vasculitis and Raynaud's phenomenon suggesting a
      collagen vascular disease. In the course of investigation, echocardiogram showed
      a possible left ventricular myxoma and computed tomography of the abdomen
      demonstrated a left adrenal tumour. Cardiac myxoma should be considered in the
      differential diagnosis of vasculitis.

PMID- 8553107
TI  - Persistence of red cell aplasia despite treatment of malignant thymoma: a case
      report.
AB  - Pure cytopenias are well-recognised associations with malignant thymoma. We
      present a case of pure red-cell aplasia (PRCA) and malignant thymoma where the
      PRCA continued to persist despite computerised tomographic scan evidence of
      regression following radiotherapy and chemotherapy.

PMID- 8553108
TI  - Sclerosing haemangioma of the lung.
AB  - An asymptomatic middle-aged women was investigated for a lung nodule detected on
      routine chest X-ray. Percutaneous needle biopsy revealed it to be a sclerosing
      haemangioma which was subsequently removed by a left lower lobectomy. The
      literature on this uncommon benign lesion is reviewed.

PMID- 8553109
TI  - Single coronary artery: a case report and review of current literature.
AB  - We present a case of a single coronary artery where the right coronary artery
      (RCA) arose from its proximal part. This rare anomaly was detected during
      elective coronary angiography in a patient with suspected coronary artery
      disease. The single coronary artery originated from the left sinus of valsalva,
      giving rise to RCA proximally and distally dividing into left anterior descending
      (LAD), ramus intermedius and left circumflex (LCX) arteries. The anginal symptoms
      in this patient was attributed to a significant stenosis at the proximal LAD
      which was subsequently dilated by coronary angioplasty. To the best of our
      knowledge, this is the first reported case of angioplasty of LAD in an anomalous
      single coronary artery.

PMID- 8553110
TI  - Pecking injury of the eye.

PMID- 8553111
TI  - The location of the cervical nerve roots on the posterior aspect of the cervical
      spine.
AB  - STUDY DESIGN: This study analyzed anatomic parameters between the midpoint of
      cervical vertebral lateral masses as seen on the superficial, posterior aspect of
      the mass and cervical nerve roots. Posterior cervical dissection was performed,
      with the midpoint of the lateral masses kept intact and the nerve roots exposed.
      OBJECTIVE: To quantitatively determine the location of the cervical nerve roots
      and the transverse foramina, indicating vertebral artery placement relative to
      the posterior aspect of the cervical spine. SUMMARY OF BACKGROUND DATA: Posterior
      plate-screw fixation of the cervical spine has been widely used to treat unstable
      fractures of the cervical spine. However, injury to the spinal nerve roots during
      the procedure remains an important concern. No previous anatomic study regarding
      the location of the cervical nerve roots relative to the posterior aspect of the
      cervical spine has been reported. METHODS: Fifteen specimens were obtained for
      study of the cervical spine. Laminectomy and partial removal of the superior and
      inferior articular facets then were performed on C2-C3 through C7-T1 to expose
      the nerve roots and dura. Photographs, containing a reference scale, were taken
      simultaneously perpendicular to the sagittal and transverse planes of the
      specimen. Using enlarged versions of the photographs, independent measurements by
      several observers were taken from the superficial, posterior center of each
      lateral mass to the nerve root superiorly and inferiorly, and to the lateral
      limits of the dura. Vertebrae from an additional 20 spines were examined to
      determine the position of the transverse foramina relative to the lateral mass of
      the vertebrae. RESULTS: The results showed that for C3-C7, the average distance
      from the superficial, posterior center of the lateral mass to the nerve root
      superiorly was 5.7 +/- 1.5 mm. Inferiorly, the average distance was 5.5 +/- 0.8
      mm. The average distance from the lateral mass to the spinal cord dura was 9.2 +/
      1.4 mm, and the average medial angle of the nerve root was 76.3 degrees +/- 4.4
      degrees. For cervical vertebrae C3-C5, the transverse foramina were situated
      medial to the posterior center of the lateral mass. At the C6 level, the
      transverse foramina were situated anterior to the posterior midpoint of the
      lateral mass. CONCLUSION: This study demonstrates that the posterior midpoint of
      the lateral mass is a safe point for initiating screw insertion.

PMID- 8553112
TI  - Application of polyvinyl alcohol hydrogel membrane as anti-adhesive interposition
      after spinal surgery.
AB  - STUDY DESIGN: Three inflammatory and adhesive changes inside the spinal canal
      were analyzed histopathologically in cats. OBJECTIVE: To investigate the
      usefulness of a polyvinyl alcohol hydrogel sheet as an interposition over the
      dura to prevent inflammatory and adhesive reaction after laminectomy. SUMMARY OF
      BACKGROUND DATA: A major concern after laminectomy is scar tissue formation that
      may result in extradural compression or make subsequent surgery to the same area
      difficult and hazardous. METHODS: Wide laminectomy was performed at L5 in 30
      adult cats. The dura was covered with a polyvinyl alcohol hydrogel sheet, free
      fat graft, or without interposition as a control. Animals were killed at 3 or 12
      weeks. RESULTS: In the control group, adhesion of the exposed dura was apparent.
      Thick, fibrous connective tissue was observed between the dura and the
      paravertebral muscles. In the fat graft group, the dura was separated from the
      scar tissue by living grafted fat. However, the dura was adherent to the grafted
      fat and fibroblasts migrated into the interstitial space. In the polyvinyl
      alcohol hydrogel group, only a thin synovium-like layer was formed around the
      polyvinyl alcohol hydrogel sheet. CONCLUSIONS: Polyvinyl alcohol hydrogel is made
      of water and alcohol, and has been shown to be nontoxic to tissues. This is
      permeable to low molecular weight, but impermeable to large cells such as
      fibroblasts. Thus, the polyvinyl alcohol hydrogel sheet prevents migration of
      inflammatory cells and subsequently reduces intraspinal canal scar tissue
      formation and adhesive reaction. Other beneficial properties are extreme
      elasticity and low friction, which eliminate mechanical reaction to the spinal
      cord. The polyvinyl alcohol hydrogel sheet is believed to be useful in
      eliminating scar tissue formation and does not interfere with the dynamic gliding
      movement of the spinal cord and nerve roots.

PMID- 8553113
TI  - 31P nuclear magnetic resonance spectroscopic evidence that canine nucleus
      pulposus and anulus fibrosus cells differ in principal organophosphorus
      biomolecules.
AB  - STUDY DESIGN: 31P Nuclear magnetic resonance spectroscopy was used to compare
      amounts and types of principal organophosphorus biomolecules in canine
      intervertebral disc tissues ex vivo. OBJECTIVE: The goal of this study was to
      compare principal organophosphorus biomolecules in nucleus pulposus, anulus
      fibrosus, and in isolated nucleus pulposus and anulus fibrosus cells. SUMMARY OF
      BACKGROUND DATA: There is no published information on principal organophosphorus
      biomolecules in disc tissues for any animal. METHODS: Canine nucleus pulposus and
      anulus fibrosus were shown by hematoxylin-eosin staining to be healthy tissues
      characteristic of adult dogs. Viable cells liberated from these disc tissues by
      sequential protease digestion were directly visualized by light microscopy of wet
      mounts. 31P nuclear magnetic resonance spectra were recorded at room temperature
      for 12 hours according to conventional published methods. RESULTS: No resonances
      were detected for intact nucleus pulposus and anulus fibrosus tissue. 31P nuclear
      magnetic resonance spectra of viable chondrocyte-like cells from anulus fibrosus
      featured two distinctive resonance peaks consistent with phosphomonoesters and
      phosphodiesters. After undigested anulus fibrosus was removed, no resonances were
      detected. 31P nuclear magnetic resonance spectra of viable chondrocyte-like cells
      from nucleus pulposus before and after removal of undigested tissue featured only
      one resonance peak consistent with phosphodiesters. CONCLUSIONS: A
      phosphomonoester-containing biomolecule is present in healthy canine anulus
      fibrosus tissue but not in nucleus pulposus tissue, nor in nucleus pulposus cells
      or anulus fibrosus cells. A phosphodiester-containing biomolecule is present
      principally in nucleus pulposus cells. This study demonstrated that canine
      chondrocyte-like cells from nucleus pulposus and anulus fibrosus are
      phenotypically distinctive in principal organophosphorus biomolecules.

PMID- 8553114
TI  - Atlanto-occipital hypermobility in subjects with Down's syndrome.
AB  - STUDY DESIGN: The upper cervical spines of 57 subjects with Down's syndrome were
      retrospectively examined, with special attention to atlanto-occipital mobility.
      OBJECTIVE: To examine the magnitude of atlanto-occipital mobility and its
      clinical significance in subjects with Down's syndrome. SUMMARY OF BACKGROUND
      DATA: Atlanto-occipital translation of more than 1 mm in adults implies
      instability. However, the normal value in children with Down's syndrome has not
      been established, and the value in Down's syndrome has not been evaluated based
      on a comparison between subjects with Down's syndrome and control subjects.
      METHODS: Measurements were made by Wiesel and Rothman's method in 38 subjects
      with Down's syndrome and 34 control subjects. RESULTS: Atlanto-occipital
      translation in the Down's syndrome group ranged from 0-6.4 mm (mean, 2.3 mm),
      whereas in the control group it ranged from 0-2.1 mm (mean, 0.61 mm). The
      difference was statistically significant. Of the 38 subjects with Down's
      syndrome, 37 were asymptomatic. CONCLUSION: The magnitude of atlanto-occipital
      translation, as expected, apparently was greater in subjects with Down's syndrome
      than in control subjects. Although the possibility of neurologic complications
      should be considered whenever unusually high atlanto-occipital mobility is seen,
      a majority of the subjects with Down's syndrome were asymptomatic.

PMID- 8553115
TI  - Magnetic resonance imaging of tuberculous spondylitis.
AB  - STUDY DESIGN: This retrospective study analyzed the magnetic resonance imaging
      characteristics of tuberculous spondylitis. OBJECTIVE: To describe the magnetic
      resonance imaging characteristics of tuberculous spondylitis and compare the
      diagnostic yield of magnetic resonance imaging versus other modalities. SUMMARY
      OF BACKGROUND DATA: Tuberculous spondylitis is not an uncommon occurrence with
      extrapulmonary disease. It requires prompt diagnosis and management. In the pre
      magnetic resonance imaging era, computed tomography was used to delineate the
      associated radiologic changes. Data are limited that describe the magnetic
      resonance imaging pattern of tuberculous spondylitis and the effect of post
      contrast enhancement. METHODS: The magnetic resonance imaging characteristics of
      28 vertebrae in 12 patients with tuberculous spondylitis were studied. RESULTS:
      The thoracic spine was the most commonly involved region, with involvement
      occurring in the thoracic spine alone in 12 vertebrae (43%) and with other areas
      of the spine in an additional five (18%). Partial involvement was detected in the
      majority of the vertebral lesions (24; 86%). Magnetic resonance imaging evidence
      of disc space involvement was apparent in only 46% of the lesions. Paraspinal
      abscess and epidural extension were documented by magnetic resonance imaging in
      71% and 61% of lesions, respectively. Decreased signal intensity on T1-weighted
      images was demonstrated in 13 vertebrae (46%), with increased signal intensity on
      T2-weighted images seen only in five (18%). CONCLUSION: Magnetic resonance
      imaging is a useful diagnostic modality for patients with suspected tuberculous
      spondylitis. Partial vertebral involvement and paraspinal and epidural extension
      were delineated. Study of the signal intensity on T1- and T2-weighted images
      revealed a pattern that may be dissimilar to that commonly reported. Post
      contrast enhancement adds more certainty to the diagnosis of tuberculous
      spondylitis.

PMID- 8553116
TI  - Identifiable risk factors for secondary neurologic deterioration in the cervical
      spine-injured patient.
AB  - STUDY DESIGN: This was a retrospective prevalence study. OBJECTIVE: A review of
      structural cervical spine injuries (fracture or dislocation) treated at a
      regional spine injury referral center from 1987 to 1992 was undertaken to
      identify and analyze patients who had secondary neurologic deterioration after
      they had arrived and had primary assessment in stable neurologic condition
      (intact or compromised, but not evolving). SUMMARY OF BACKGROUND DATA: Multiple
      case reports and cohort studies have suggested possible risk factors for late
      neurologic deterioration without probabilities analysis. METHODS: Information was
      obtained retrospectively from clinical records and radiographs. Three-hundred
      twelve cases were reviewed. Thirty-one were excluded and 281 were analyzed.
      RESULTS: An index group of 15 patients (5%) had motor neurologic deterioration
      after primary assessment at the referral center. Control group "A" was composed
      of 70 patients (25%) who had a motor neurologic deficit on admission and did not
      deteriorate. Control group "B" was the balance of 196 patients (70%) with
      structural cervical injuries, but no neurologic compromise. Factors
      distinguishing the index group from control subjects included flexural mechanism
      of injury and chronic multilevel spinal arthritis with ankylosis. All secondary
      deteriorations occurred with the injury level caudad to the fourth cervical
      vertebra. Routine three-view cervical radiographs were relatively insensitive in
      detecting injury in the index group compared with the pooled control subjects.
      Patients' ability to comply with recommended treatment was not a factor in
      secondary deteriorations and there generally was no identifiable precipitant
      event before secondary deterioration. CONCLUSION: Cervical traumatized patients
      with flexural injury or chronic multilevel spinal arthritis with ankylosis are at
      increased risk of having secondary motor neurologic deterioration.

PMID- 8553117
TI  - Are radiologic changes in the thoracic and lumbar spine of adolescents risk
      factors for low back pain in adults? A 25-year prospective cohort study of 640
      school children.
AB  - STUDY DESIGN: This report was based on a 25-year prospective cohort study and
      designed as a self-administered questionnaire with low back pain as the main
      topic. OBJECTIVE: To identify whether radiologic changes in the thoracic and
      lumbar spine and a history of low back pain in the adolescent period represent
      risk factors for low back pain in adults. SUMMARY OF BACKGROUND DATA: Six-hundred
      forty 14-year-old school children were examined with x-rays of the thoracic and
      lumbar spine and registered by the school doctor regarding a history of low back
      pain. METHODS: All of the x-rays and the short journals from the school doctor's
      registration were reviewed. This primary information was the basis of the
      investigation 25 years later. RESULTS: Eleven percent of the cohort had a history
      of low back pain in adolescence, and the results showed an 84% lifetime
      prevalence of low back pain in these subjects as adults and an increased
      frequency of low back pain the last month and week before they answered the
      questionnaire, compared with the rest of the cohort. These problems were
      associated with increased morbidity and decreased working capacity. Thirteen
      percent had radiologic abnormalities, mainly Scheuermann changes, in the thoracic
      and lumbar spine as adolescents, with no positive correlation to low back pain in
      this period. Unlike other reports, our results did not confirm a positive
      correlation between x-ray changes in the lower spine in adolescents and a higher
      prevalence of low back pain in adults. Stepwise logistic regression analyses
      showed that low back pain in the growth period and familial occurrence of back
      disease are important risk factors for low back pain later in life, with an
      observed probability of 88% if both factors are present. CONCLUSION: This study
      suggests that low back pain in the growth period is "a real problem," with a
      trend toward aggravation as time passes. Thus, implementing preventive measures
      in schools may be very important.

PMID- 8553118
TI  - The effects of spinal flexion and extension exercises and their associated
      postures in patients with acute low back pain.
AB  - STUDY DESIGN: A prospective randomized clinical trial compared the effects of
      flexion and extension back exercises and postures among soldiers with acute low
      back pain. OBJECTIVE: To compare the immediate effects of back exercise on
      functional status, spinal mobility, straight leg raising, pain severity, and
      treatment satisfaction, and to determine whether spinal exercise during the acute
      stage of low back pain reduces recurrent episodes of low back pain. SUMMARY OF
      BACKGROUND DATA: Conflicting reports exist concerning the efficacy of spinal
      flexion and extension exercises in patients with low back pain of varying
      duration. Poor study design and lack of functional outcomes characterize many of
      these studies. METHODS: One-hundred-forty-nine subjects with acute low back pain
      received flexion exercise and posture (n = 57), extension exercise and posture (n
      = 62), or no exercise or posture (n = 30) for 8 weeks. Outcomes were assessed 1,
      2, 4 and 8 weeks after treatment onset. A questionnaire assessed the recurrence
      of low back pain 6-12 months after study entry. RESULTS: Flexion and extension
      exercise groups did not differ in any outcome over 8 weeks. After 1 week, both
      exercise groups had reduced disability scores, a higher proportion returning to
      work, and fewer subjects with a positive straight-leg raise compared with the
      control group. There was no difference among groups regarding recurrence of low
      back pain after 6-12 months. CONCLUSIONS: There was no difference for any
      outcomes between the flexion or extension exercise groups. However, either
      exercise was slightly more effective than no exercise when patients with acute
      low back pain were treated.

PMID- 8553119
TI  - Evaluation of lumbar spine fusion. Plain radiographs versus direct surgical
      exploration and observation.
AB  - STUDY DESIGN: In a retrospective study, the incidence of false positive and false
      negative interpretation of x-rays for solid spinal arthrodesis with spinal
      instrumentation was evaluated in 75 patients. OBJECTIVE: To evaluate the accuracy
      of the interpretation of x-rays for diagnosing solid spinal arthrodesis in
      patients with spinal instrumentation. SUMMARY OF BACKGROUND DATA: This
      retrospective study compared spinal fusion, as determined by direct observation
      and radiographic evaluation, in 75 patients with instrumented lumbar fusions
      using multiple devices. The fusions included posterolateral fusions or
      posterolateral with interbody fusions. Autograft, allograft, and a combination of
      these also were used. METHODS: A single blinded examiner reviewed all x-rays
      immediately before the spinal hardware was removed and the fusion mass was
      explored by the surgeon. RESULTS: There was a positive correlation between x-rays
      and the observations at the time of surgery in only 68% of the patients.
      CONCLUSION: This study indicates that the accuracy of x-ray interpretation for
      spinal arthrodesis is only 68%. The L4-L5 level was the most difficult level to
      fuse and the most difficult to interpret using x-rays. Patients with persistent
      back pain, when nonmechanical causes have been ruled out, should be considered
      for surgical exploration of the fusion mass even if x-rays appear to indicate a
      solid fusion.

PMID- 8553120
TI  - Use of sensory-evoked potentials recorded from the human occiput for
      intraoperative physiologic monitoring of the spinal cord.
AB  - STUDY DESIGN: This is a report of a prospective case series. OBJECTIVE: The
      purpose of this study was to determine whether evoked potential activity recorded
      from occipital scalp electrodes in humans is similar to that recorded in animals,
      and to evaluate the independence of this activity from the classical
      somatosensory-evoked potential. SUMMARY OF BACKGROUND DATA: Intraoperative
      somatosensory-evoked potentials can be of limited usefulness in predicting spinal
      cord injury because they are transmitted primarily through the dorsal columns,
      and therefore do not reflect integrity of important ventral pathways. It recently
      has been shown in animal studies that a sensory-evoked potential recorded from
      the cerebellum is mediated via ventral tracts and is useful as an adjunct to the
      somatosensory-evoked potential in spinal cord monitoring. METHODS: Twenty-five
      patients undergoing spinal or posterior fossa surgery were consecutively entered
      into the study. Evoked responses were recorded transcranially from over the
      cerebellar hemispheres and from the vertex. Recordings were made directly from
      the surface of the cerebellar hemispheres in seven of these patients. RESULTS:
      Waveforms could be recorded and reproduced in all but one of the patients. The
      overall appearance of the occipital recordings was similar to the appearance of
      responses obtained in animals. The mean latency of the first negative peak
      recorded from the ipsilateral occiput was 33.0 msec (standard deviation, 3.7
      msec) compared with 52.4 msec (standard deviation, 6.1 msec) for the
      somatosensory-evoked potential. In addition, the amplitude of this response (0.35
      microV; standard deviation, 0.20 microV) was independent of the amplitude of the
      somatosensory-evoked potential (0.76 microV; standard deviation, 0.69 microV). In
      five cases, one evoked potential could be recorded in the absence of the other.
      Recordings from the surface of the cerebellum were of the same morphology, but of
      greater amplitude than the transcranial recordings. CONCLUSION: Evoked responses
      can be reliably recorded from over the occiput and show characteristics
      independent of the classical somatosensory-evoked potential. These responses are
      very similar to the cerebellar-evoked potential recently characterized in animals
      and may provide a method for assessing the physiologic integrity of the ventral
      tracts of the spinal cord in humans.

PMID- 8553121
TI  - Incomplete spondylolysis and healing. A study of ancient Canadian Eskimo
      skeletons.
AB  - STUDY DESIGN: Skeletons of ancient Canadian Eskimos subjected to arctic
      weathering presented an unusual opportunity for direct observation of all stages
      of spondylolysis. OBJECTIVE: To explore early stages of incomplete lysis, a
      phenomenon difficult to observe radiographically. SUMMARY OF BACKGROUND DATA:
      Although lumbar spondylolysis most often appears to be a stress fracture that may
      proceed to complete separation, its early stages have been difficult to
      visualize. METHODS: Vertebrae were examined for even minute lytic defects in the
      general region of pars interarticularis and the results were correlated with age
      at death. RESULTS: Spondylolysis was found in 51 individuals, with 110 separate
      sites (sides) affected. At 34 of these sites, all but two in adolescents or young
      adults, the lysis was incomplete. Incomplete lysis affected the superior margin
      of the neural arch more often than the inferior margin, and the right side more
      often than the left. CONCLUSION: Spondylolysis first became recognizable as
      incomplete stress fractures during adolescence, with most progressing to complete
      lysis in young adulthood. New fractures continued to develop in young adults, but
      most healed by middle adulthood. After 45 years of age, the overall frequency of
      spondylolysis declined, indicating that even complete defects occasionally
      healed.

PMID- 8553122
TI  - Progressive scoliosis in Dubowitz syndrome.
AB  - STUDY DESIGN: This case report describes a 17-year-old male with Dubowitz
      syndrome in whom a progressive left thoracic scoliosis developed that required
      surgical correction. OBJECTIVE: Scoliosis associated with Dubowitz syndrome had
      not been previously described among the orthopedic manifestations of this rare
      syndrome. A review of the literature and the surgical treatment of this patient
      is presented. SUMMARY OF BACKGROUND DATA: Dubowitz syndrome is a rare autosomal
      recessive disorder characterized by microcephaly, craniofacial abnormalities,
      eczematous skin rash, delayed skeletal maturation, and shortness of stature. The
      orthopedic manifestations of this condition primarily involve the hands and feet
      with brachyclinodactyly of the fifth finger and syndactyly of the second and
      third toes. Spinal deformity in these individuals is not well described in the
      literature. METHODS: Over a 2-year period, the patient's scoliosis progressed to
      88 degrees, resulting in severe truncal imbalance without neurologic sequelae. A
      posterior spinal fusion with segment instrumentation alone was used to correct
      the deformity. RESULTS: After surgery, excellent restoration of spine sagittal
      and coronal plane alignment was achieved, resulting in improved sitting and
      standing balance. CONCLUSION: Patients with Dubowitz syndrome may be at risk of
      having a progressive, rigid scoliosis. These individuals may need to be observed
      over a prolonged period for the development of spinal deformity because of the
      potential for extended delay in skeletal maturation.

PMID- 8553123
TI  - Intramedullary spinal cord germinoma.
AB  - STUDY DESIGN: A very rare case of intramedullary spinal cord germinoma is
      described. OBJECTIVE: To increase knowledge about the pathogenesis and treatment
      of intramedullary spinal cord germinoma. SUMMARY OF BACKGROUND DATA: Primary
      intramedullary spinal cord germinoma is very rare and only two cases have been
      previously reported. METHODS: A case of intramedullary spinal cord germinoma with
      complete paraplegia is presented. The diagnosis was determined by biopsy.
      RESULTS: After local irradiation of 46 Gy, the tumor disappeared completely.
      CONCLUSION: Irradiation therapy effectively treated this tumor, as shown
      radiologically, although the patient remained paraplegic.

PMID- 8553124
TI  - Intradural metastasis to the cauda equina from carcinoma of the anus.
AB  - STUDY DESIGN: This is a report of a man with carcinoma of the anus and intradural
      metastasis to the cauda equina. OBJECTIVE: To perform a laminectomy with tumor
      removal for relief of pain. SUMMARY OF BACKGROUND DATA: Only 25 cases of
      intradural spinal metastasis have been reported in the English literature. This
      is the first report of a metastatic case, moving from the carcinoma of the anus
      to the cauda equina. METHODS: Magnetic resonance imaging showed an ill-defined
      mass, with central necrosis, to the cauda equina. The possibility of intradural
      metastasis to the cauda equina was indicated by unique pain symptoms. RESULTS:
      The patient's back pain subsided after total laminectomy of L3-L5 with subtotal
      removal of the tumor. The residual tumor became smaller with postoperative
      radiation. CONCLUSION: Magnetic resonance imaging is a good diagnostic choice in
      this situation. The cause of the metastasis was unclear, but it was presumed to
      have occurred through the perineural lymphatic ducts. Laminectomy with tumor
      removal is feasible for relieving pain and demonstrating pathology.

PMID- 8553125
TI  - Spine update. Functional restoration.
AB  - Therapeutics as diverse as surgery, manipulation, and behavior modification can
      be intended to restore function for people with spinal disorders. However, the
      term "functional restoration" was coined by Tom Mayer and Vert Mooney to specify
      interdisciplinary programmatic care geared toward minimizing disability.
      Functional restoration emphasizes physical and behavioral improvements over pain
      eradication and relies heavily on guidance from repeated quantification of
      function. Unlike a comprehensive review, this report is meant to briefly update
      the reader on selected issues in functional restoration and to suggest directions
      for future developments.

PMID- 8553126
TI  - Historical perspective. Joseph Janse.
AB  - The purpose of this presentation is to acknowledge the pioneering work of a key
      historical figure who contributed to the available knowledge in anatomy and
      biomechanics, developed political and social infrastructure to promote the
      maturation and standardization of chiropractic education, and influenced a
      paradigmatic shift away from a monocausal belief in the origin of disease.
      Literature search and archives retrieval were used. Janse was a man with personal
      intellectual integrity and whose personal commitment was driven by a family
      experience. Evidence shows that Janse took bold initiatives to influence the
      chiropractic profession and give it the opportunity to develop as a legitimate
      healthcare discipline. Janse was a visionary clinical scientist and educator
      whose 38-year tenure as president of a chiropractic college enabled him to
      influence the course and development of his profession.

PMID- 8553127
TI  - Biomechanical testing of the spine. Load-controlled versus displacement
      controlled analysis.
AB  - Mechanical testing of the spine can be carried out in either a load-controlled or
      a displacement-controlled manner. Each method requires certain assumptions and
      offers different advantages. Dr. W. Thomas Edwards believes that displacement
      controlled testing most accurately reflects the in vivo environment, while Drs.
      Vijay Goel, David Wilder, and Malcolm Pope support the use of the load-controlled
      method as most logical and easily standardized.

PMID- 8553128
TI  - Quantitative magnetic resonance imaging of the lumbar spine. Potential for
      investigations of water content and biochemical composition.
AB  - Quantitative magnetic resonance imaging (relaxation time and proton density
      measurements) has gained increasing interest as a noninvasive way to study
      changes in water content and biochemical composition of lumbar intervertebral
      discs and vertebral bodies. This article reviews the current methodological
      problems and the feasibility of quantitative magnetic resonance imaging in the
      lumbar spine for investigations on water content and biological composition. This
      technique does not allow direct quantification of water content. Although
      biochemical variations may sensitively influence relaxation times and proton
      density under in vitro conditions, it is not feasible to obtain sufficiently
      reliable and specific information to monitor biochemical alterations associated
      with lumbar disc pathology in vivo.

PMID- 8553129
TI  - [Value of imaging methods in radiotherapy of invasive breast carcinoma].

PMID- 8553130
TI  - [Analysis of the quality of preoperative diagnosis with magnetic resonance
      imaging of intervertebral disk lesions of the lumbar spine].

PMID- 8553131
TI  - [Modified double contrast examination of the stomach in obese patients after
      vertical gastroplasty].

PMID- 8553132
TI  - [Military roentgenology in former Austria before the First World War].

PMID- 8553133
TI  - Essential drugs list essentials.

PMID- 8553134
TI  - ABC of mandatory health insurance.

PMID- 8553135
TI  - HIV/AIDS testing remains prickly affair.

PMID- 8553136
TI  - Health expenditure and finance in SA.

PMID- 8553137
TI  - Emergency treatment of acute sustained tachyarrhythmias.

PMID- 8553138
TI  - The eclampsia trial--implications for South Africa.

PMID- 8553139
TI  - Highlights of the World Health Assembly, Geneva, 1995.

PMID- 8553140
TI  - Usefulness of cancer registries in epidemiological research and cancer control.
      Advisory Committee, National Cancer Registry.

PMID- 8553141
TI  - A health informatics policy for South Africa?

PMID- 8553142
TI  - Maternal deaths in Bloemfontein, South Africa--1986-1992.
AB  - OBJECTIVE: Determination of the maternal mortality ratio and the main causes of
      maternal death. SETTING: Pelonomi Hospital, a tertiary care and referral hospital
      in Bloemfontein. METHODS: Review of prospectively completed structured
      questionnaires on all maternal deaths from 1986 to 1992. RESULTS: The maternal
      mortality ratio at our institution was 171 per 100 000 live births. Haemorrhage
      (25%), infection (24%) and hypertensive disease (18%) were the most important
      causes of death. Seventy-one per cent were direct obstetric deaths and 23%
      indirect; in the remaining 6%, the cause was uncertain. Of all deaths, 35% were
      considered preventable. CONCLUSIONS: The maternal mortality ratio has decreased
      since our previous report for the period 1980-1985, and haemorrhage has replaced
      infection as the leading cause of death.

PMID- 8553143
TI  - Identification of depression in a rural general practice.
AB  - Major depression is underdiagnosed by general practitioners, but the reasons for
      this are not clear. This study aimed to establish the prevalence of major
      depression and coexisting generalised anxiety disorder in a rural general
      practice in the Orange Free State. It also assessed the predictive value of a
      screening questionnaire for use by general practitioners. The two practitioners
      evaluated 858 patients over a 4-week period. Those who met the screening
      criteria, together with a random sample of 60 patients who did not, were re
      evaluated by a registrar in psychiatry who was unaware of the findings of his
      colleagues. Of the patients studied, 134 (15.6%) had major depression; 59 of
      these (44.0%) also had coexisting generalised anxiety disorder. The general
      practitioners had correctly diagnosed major depression in 32 patients (3.7%)
      before the study started. The screening questionnaire had a 42% chance of
      correctly identifying a patient with depression and a 97% chance of correctly
      identifying a patient who did not have major depression. Both practitioners were
      equally capable at identifying major depression. The study confirmed both the
      high prevalence of depression in a rural general practice and its low
      identification rate. It also showed the advantage of using a screening
      questionnaire to alert practitioners to the possibility of depression in their
      patients.

PMID- 8553144
TI  - [Masked depression].
AB  - Masked depression is a condition in which the classic affective and cognitive
      symptoms of depression are hidden behind a variety of somatic complaints or
      behavioural problems. Patients suffering from masked depression are usually
      incorrectly diagnosed and treated symptomatically with little success. The
      condition is often encountered in the medical literature from the late 1960s to
      the early 1980s, but little has been published about it in recent years. This
      review discusses the changing ideas and approach with regard to masked depression
      and examines whether they are still relevant today. The literature published in
      each of the previous decades is studied and specific attention is given to
      cultural differences in a South African context. Although little has been
      published on masked depression in the past few years, somatic complaints in
      depression are still regularly examined in the literature. A significant number
      of patients with depression are still not correctly diagnosed and masked
      depression therefore remains relevant. Doctors should be aware of the presenting
      complaints in these patients and should understand the reasons for somatisation.

PMID- 8553145
TI  - Utilisation of maternity services by black women in rural and urban areas of the
      Orange Free State.
AB  - An epidemiological survey was undertaken to evaluate the utilisation of maternal
      services for black women in the Orange Free State. Two hundred and forty clusters
      were selected from the rural (farms) and urban (local authorities) black
      population and eight households were interviewed in each cluster. Information was
      gathered from 237 rural women (from 959 households) and 168 urban women (from 926
      households) who had delivered a baby or aborted during the preceding year.
      Antenatal care was received by 71% of the rural women and 87% of the urban women.
      Rural women delivered at home in 60% of cases while 37% delivered in hospitals.
      Only 23% of urban women delivered at home while 67% of their deliveries were
      conducted in hospitals. Nurses supervised deliveries in both instances in more
      than 60% of cases, but in rural areas traditional midwives managed 26% of the
      confinements. The conclusions are that the maternity service was largely provided
      by nurses and was predominantly limited to hospitals and homes. It is recommended
      that the quality of service be upgraded and more emphasis placed on midwife
      obstetric units.

PMID- 8553146
TI  - The effects of buserelin microparticles on ovarian function in healthy women.
AB  - OBJECTIVE: To investigate the tolerance, pharmacokinetics and pharmacodynamics of
      the microparticle formulation of buserelin, when it was administered
      subcutaneously. DESIGN: A single-blind, randomised, parallel-group design was
      used to investigate the duration of suppression of ovarian function associated
      with doses of 1.8 3.6 and 7.2 mg buserelin administered subcutaneously as
      microparticles. SETTING: The study was carried out at the Hoechst Research Centre
      for Clinical Pharmacology, Department of Pharmacology, University of the Orange
      Free State, Bloemfontein. PATIENTS: Thirty-two health premenopausal female
      volunteers aged between 19 and 39 years and weighing between 52 and 85 kg
      completed the study. OUTCOME MEASURES: Serum progesterone and oestradiol
      concentrations were measured twice weekly until normal ovarian function resumed,
      i.e. when serum progesterone concentrations increased to at least 8 nmol/l (a
      sign of ovulation) and oestradiol concentrations increased to values above 300
      pmol/l. Serum and urinary concentrations of buserelin were measured at the same
      times as those of progesterone and oestradiol. RESULTS: Doses of 1.8 3.6 and 7.2
      mg elicited anovulation for mean periods of 52, 77 and 113 days and suppressed
      ovarian production of oestrogen for 19, 38 and 69 days. Resumption of normal
      ovarian function occurred when serum buserelin concentrations decreased to
      between 0.03 and 0.05 microgram/ml. The correlation coefficient between dose and
      duration of anovulation was 0.75; the correlation coefficient between dose and
      duration of suppression of oestrogen production was 0.76. CONCLUSION: Apart from
      minor side-effects such as hot flushes, vaginal spotting and acne, the compound
      was tolerated well. We conclude that a good relationship exists between dose and
      duration of suppression of ovarian function. Doses of 3.6 - 7.2 mg buserelin
      should suppress oestrogen production for approximately 6 - 9 weeks and ovulation
      for 11 - 16 weeks.

PMID- 8553147
TI  - Multiple doses of trandolapril do not affect warfarin pharmacodynamics.
AB  - OBJECTIVE: The effects of multiple doses of trandolapril (a new angiotensin
      converting enzyme inhibitor) on the pharmacodynamics of a single 25 mg dose of
      warfarin were investigated in 19 men. DESIGN: A double-blind, placebo-controlled
      cross-over design was used. The study consisted of two periods of 13 days each,
      during which subjects received either trandolapril 2 mg or placebo once daily
      according to a randomisation plan. Warfarin was given on day 8 of each of these
      periods. SETTING: The study was carried out at the Hoechst Research Centre for
      Clinical Pharmacology, Department of Pharmacology, University of the Orange Free
      State, Bloemfontein. PATIENTS: Nineteen healthy white men aged between 18 and 28
      years and weighing between 65 and 98 kg volunteered for the study. OUTCOME
      MEASURES: Prothrombin time (PT) and coagulation factors II, VII, IX and X were
      measured before and sequentially up to 6 days after warfarin administration.
      Areas under the PT and coagulation factor time curves for warfarin + trandolapril
      were compared with the corresponding areas for warfarin + placebo. The two
      treatment combinations were also compared at each measuring time. RESULTS: The
      point estimate for the ratio of the treatment means of warfarin + trandolapril
      relative to warfarin + placebo for PT was 97% (90% confidence interval: 90%
      103%). The corresponding value for factor VII was 97% (90% confidence interval:
      91%-102%). CONCLUSION: The concomitant administration of trandolapril did not
      affect the pharmacodynamic effects of warfarin.

PMID- 8553148
TI  - Determination of glomerular filtration rate with radionuclide renography and
      direct urinary activity quantitation.
AB  - OBJECTIVE: The direct urinary activity quantitation method is quick
      (approximately 40 minutes), requires only a single blood sample, is performed as
      part of standard renal scanning and shows high accuracy compared with 24-hour
      creatinine clearance. The purpose was to evaluate the practical application and
      accuracy of this technique at our clinic. DESIGN: Direct urinary activity
      quantitation was done in patients scheduled for routine radionuclide renography
      and compared to standard multiple-blood-sample techniques by means of Cr-51-EDTA
      and Tc-99m-DTPA. SETTING: Academic Medical Complex, Department of Nuclear
      Medicine, Universitas Hospital, Bloemfontein. PARTICIPANTS: Fifteen patients
      scheduled for routine radionuclide renography (glomerular filtration rate (GFR)
      determination) were voluntarily enrolled in the study. The GFRs of selected
      patients varied over a wide range. Possible obstructive uropathy was excluded.
      MAIN OUTCOME MEASURES: GFRs obtained by the direct urinary method were compared
      with GFRs determined by multisample Cr-51-EDTA and Tc-99m DTPA. RESULTS: GFRs
      from the direct urinary method compared with multisample Tc-99m-DTPA showed
      differences from -19.85 to 22.95 ml/min with a mean of 0.2 (+/- 12.25) ml/min (r
      = 0.93). When compared with multisample Cr-51 EDTA, differences ranged from 
      34.35 to 21.05 ml/min with a mean of -4.25 (+/- 16.08) ml/min (r = 0.90).
      CONCLUSION: The direct urinary activity technique is CONCLUSION: The direct
      urinary activity technique is easily applied and highly accurate compared with
      previous standardised multisample radionuclide techniques for determination of
      GFR.

PMID- 8553149
TI  - The protection of personal and medical data--a call for confidentiality.
AB  - Personal data and privacy are increasingly being threatened by a boom in
      technological development--the replacement of conventional networks of
      communication with the perfected combination of computer and telecommunications.
      The subsequent high degree of transparency has the potential to damage the
      individual's right to 'informational self-determination'. The most common ways of
      unlawfully entering a computer data system, the reasons why an individual's
      information is treated as confidential and the ethical issues involved,
      international and local statutory instruments that protect such personal
      information, and ways to stop the outflow of personal information are discussed.

PMID- 8553150
TI  - Characterisation of penA and tetM resistance genes of Neisseria gonorrhoeae
      isolated in southern Africa--epidemiological monitoring and resistance
      development.
AB  - OBJECTIVE: To investigate penA and tetM resistance gene variation of Neisseria
      gonorrhoeae in order to define gene types for epidemiological monitoring and
      resistance development. DESIGN: Isolates of N. gonorrhoeae which were susceptible
      and resistant to penicillin and/or tetracycline were selected. Strains comprised
      South African isolates (22 from Bloemfontein, 13 from Transvaal, 20 from the
      Cape) and 15 Botswana and 4 Namibia isolates. The penA genes (2 kb) of all
      strains and tetM genes (765 bp) of 11 high-level tetracycline-resistant strains
      were amplified and restricted with HpaII. RESULTS AND CONCLUSIONS: Twelve
      different HpaII fingerprint patterns were obtained from the 74 isolates analysed
      for penicillin-binding protein (PBP) 2 gene (penA) alterations. Focusing on the
      transpeptidase domain, 25 isolates (3 whole gene patterns, minimal inhibitory
      concentrations (MICs) < or = 0.03-0.125 micrograms/ml) had restriction sites
      equivalent to those previously described for a susceptible strain. Of the
      remaining 9 PBP 2 gene groups, 25 strains fell into a designated group E.
      Penicillin/ penicillin + clavulanic acid MICs determined on these group E
      isolates gave a range of 0.125-2.0 micrograms/ml, although MICs against 4 strains
      were < or = 0.03 micrograms/ml. MICs of penicillin/penicillin + clavulanic acid
      for the 24 isolates that contained altered PBP 2 transpeptidase gene regions not
      designated group E were only < or = 0.03-0.125 micrograms/ml. The lack of a HpaII
      restriction site at nucleotide 1934 in the PBP 2 gene of group E strains was
      indicative of a small terminal region of N. cinerea DNA. This gene block, which
      was found in all the southern African areas studied, appears to predispose
      isolates to increased penicillin resistance. The 25.2 MDa conjugative plasmid
      carrying the tetM resistance determinant was readily demonstrated in 11
      Botswana/Namibia isolates exhibiting high-level resistance to tetracycline (MICs
      > or = 16 micrograms/ml). The tetM gene was shown to be of the American type.

PMID- 8553152
TI  - Recertification for general practitioners.

PMID- 8553151
TI  - Chronic fatigue syndrome. Committee for Science and Education, Medical
      Association of South Africa.
AB  - OBJECTIVE: To acknowledge the clinical syndrome chronic fatigue syndrome (CFS)
      and outline the diagnostic criteria and reasonable management. OUTCOMES: Attempt
      at containment of treatment cost and improvement of the quality of care of
      patients with CFS. EVIDENCE: Delphi-type commentary from 20 expert clinicians and
      appropriate organisations. Limited literature survey. VALUES: To clarify the
      reasonable management of CFS amid conflicting clinical opinion on a condition of
      concern to patients, funders and doctors. An adaptation of an existing guideline
      was sent to organisations and individuals for comment. Comments received were
      included in this guideline where possible. BENEFITS, HARMS AND COSTS. To
      acknowledge a clinical syndrome with a reasonable approach to management
      considering the cost implications. No cost analysis was done. RECOMMENDATIONS: To
      recommend the following: (i) diagnostic criteria for CFS; (ii) potential
      differential diagnoses and possible investigations; and (iii) management
      protocol. VALIDATION: The draft guidelines were subjected to external review by
      individual doctors who are acknowledged CFS treaters, doctor groups and the
      patient support group. There were major disputes about the content, with the
      responses falling into two groups: those who do not believe CFS is a
      distinguishable illness, and those who do. DEVELOPER AND FUNDING: The Committee
      for Science and Education, Medical Association of South Africa. ENDORSEMENTS:
      Medical Association of South Africa and national health care organisations (see
      list at the end of the document).

PMID- 8553153
TI  - Heart transplantation in South Africa--the sad reality.

PMID- 8553154
TI  - Transmyocardial laser revascularisation in South Africa.

PMID- 8553155
TI  - Attack on the private sector--the real reason?

PMID- 8553156
TI  - Muslim customs regarding autopsies.

PMID- 8553157
TI  - Protein energy malnutrition in the Bloemfontein area.

PMID- 8553158
TI  - Addressing oesophageal cancer--masisebenzisane sakhane sinyamezelane!

PMID- 8553159
TI  - Sexually transmitted diseases--time for action.

PMID- 8553160
TI  - Antibodies to HCV and HTLV-I in a group of HIV-seropositive STD patients.

PMID- 8553161
TI  - The use of low-dose acetazolamide to prevent mountain sickness.

PMID- 8553162
TI  - Hepatitis B vaccination.

PMID- 8553163
TI  - Relationships between general practitioners and specialists.

PMID- 8553164
TI  - Alternative medicine--a doctor's perspective.

PMID- 8553165
TI  - Alternative medicine--a doctor's perspective.

PMID- 8553166
TI  - Bowing out but standing tall: Jan van der Merwe. Interview by Ina van der Linde.

PMID- 8553167
TI  - [Autotransfusion in sero-positive patients, why not?].

PMID- 8553168
TI  - [Bone marrow transplantation with positive hepatitis B and C virus tests: are we
      incumbent with the law?].

PMID- 8553169
TI  - [Results of a series of 104 consecutive bilateral bone marrow biopsy specimens in
      lymphoproliferative disorders].
AB  - PURPOSE: To establish the incidence of discordance in a series of bilateral bone
      marrow biopsies (b-BMB) in lymphoproliferative disorders and to determine whether
      this might lead to changes in the present treatment of each patient. MATERIAL AND
      METHODS: Between March/1988 and February/1995, 89 patients underwent bilateral
      bone marrow biopsy (104 b-BMB). Seventy-six underwent one b-BMB; 11 two b-BMB and
      2 patients three b-BMB. Sixty-eight b-BMB were done at diagnosis of the disease
      and 36 for reassessment prior to ABMT. The distribution of the b-BMB by diagnosis
      was as follows: 54 non-Hodgkin's lymphoma (NHL) -23 low grade NHL and 31
      intermediate/high grade NHL-, 44 Hodgkin's disease (HD), 4 multiple myeloma (MM),
      1 splenic lymphoma with villous lymphocytes and 1 MM+HD. Specimens were obtained
      under local anaesthesia with a Jamshidi gauge 8 needle. The biopsies were fixed,
      decalcified, embedded in paraffin wax and the section cuts were stained
      (haematoxylin and eosin, Giemsa, Wilder--reticulin--and Masson--collagen--).
      RESULTS: There was discordance in 5 of the 104 b-BMB (4.8%), but only in four of
      them was this related to the presence of bone marrow disease, so that incidence
      falls to 3.8%. Three of them were obtained at diagnosis of the disease (low grade
      NHL, high grade NHL and HD) and one during reassessment before ABMT. On
      considering only the specimens that had bone marrow infiltration (19 cases: 14 at
      diagnosis and 5 in reassessment before ABMT), the absence of concordance in four
      of them implies that if only unilateral biopsy had been carried out, up to 21% of
      the cases might have been missed. In one of these patients (HD) this finding led
      us to replace autologous bone marrow transplantation by autologous peripheral
      stem cell transplantation. CONCLUSION: On the basis of these data, the use of
      bilateral bone marrow biopsy specimens may be justified in lymphoproliferative
      disorders, both at the time of diagnosis and in reassessment prior to ABMT--when
      the bone marrow was initially infiltrated.

PMID- 8553170
TI  - [First evaluation of the Variant haemoglobin analyzer (Bio-Rad)].
AB  - PURPOSE: The analytical performance of the first automated HPLC analyzer of
      haemoglobins A2 and Foetal is presented. RESULTS: The analyzer shows an
      imprecision within-run between 0.66-2.7% and between-run 1.8-6.44. Correlation
      index with manual methods were r = 0.965 (p < 0.005) for Hb A2 and r = 0.999 (p <
      0.0001) for Foetal Hb and the reference values of an adult population were
      established; Hb A2 (1.98-2.94%) and Hb F (0-0.95%). Several chromatograms of
      haemoglobinopathies are presented. CONCLUSIONS: These results validate the method
      to resolve the increased demand of these parameters.

PMID- 8553171
TI  - [Expression of von Willebrand's disease in endothelial cord cell from a type 1
      patient. Discrepancies between clinical manifestations and laboratory tests].
AB  - PURPOSE: The reactivity of subendothelium generated by endothelial cells attained
      from the umbilical cord of a newborn girl from a patient with type I von
      Willebrand's disease was evaluated. MATERIAL AND METHODS: Platelet adhesiveness
      was assessed by means of "ex vivo" blood perfusion systems (shearing coefficients
      from 300 to 1,300 s-1), on umbilical artery subendothelium and over the
      extracellular matrix (ECM) generated by cultured endothelial cells attained from
      the umbilical cord of a newborn baby from a type I von Willebrand mother.
      RESULTS: By means of an ELISA technique, a significant reduction of both the vWF
      secreted into the culture (p < 0.05) and of that associated with ECM (p < 0.05)
      was noticed. The two subendothelial surfaces examined supported a lesser extent
      of platelet adhesion than the control surfaces from healthy individuals in the
      perfusion tests at 1,300 s-1 (p < 0.05). The experimental results did not agree
      with the lack of clinical manifestations and laboratory abnormalities in the
      propositus at age 3. CONCLUSIONS: These findings suggest that the endothelial
      cells cultured from the tissues of a newborn baby from a type I von Willebrand
      woman expressed less vWF, at the same time confirming the importance of vWF bound
      to connective tissue in sustaining platelet adhesion. The data attained here
      illustrate the complex model of inheritance of moderate von Willebrand's disease,
      along with the technical limitations of cell culture studies. Such observations
      must be borne in mind whenever any experimental approach is performed with
      material attained from ill-differentiated tissues such as the umbilical cord
      vein.

PMID- 8553172
TI  - [Relationship between Epstein-Barr virus and lymphoproliferative syndromes in
      patients without immunodeficiency].
AB  - PURPOSE: The relationship between Epstein-Barr virus (EBV) and infectious
      mononucleosis, pharyngeal carcinoma and Burkitt's lymphoma is well known. Further
      relationship seems to exist between EBV and the lymphoproliferative syndromes
      appearing in immunodeficient subjects. The present work is aimed to study the
      possible relationship between the virus and the lymphoproliferative syndromes
      presented by people without any apparent immunodeficiency. PATIENTS AND METHODS:
      The presence of antibodies against different antigens of the virus was analysed.
      Antibodies against the viral capsid antigen were studied along with those against
      the early antigen and the viral core antigen in 55 patients with
      lymphoproliferative syndromes, of whom 38 had non-Hodgkin's lymphoma and 17 had
      acute lymphoblastic leukaemia, and none of them had immunodeficiency. RESULTS:
      Significantly higher geometric means of the titres against capsid antigen and of
      the prevalence of antibodies against early antigen were seen in the patients with
      non-Hodgkin's lymphoma with respect to the control group. On the contrary,
      patients with acute lymphoblastic leukaemia showed lower immunologic response
      than the control group, although the difference was not significant for any of
      the antibodies under study. CONCLUSIONS: The higher immunologic response against
      EBV and its reactivation in non-Hodgkin's lymphoma would suggest that such agent
      could play a role favouring the onset of the disease, if not as a direct
      aetiological factor.

PMID- 8553173
TI  - [Antiphospholipid antibodies in women with habitual abortions. Treatment with
      prednisone and acetylsalicylic acid during pregnancy].
AB  - PURPOSE: To discover the prevalence of antiphospholipid antibodies in women with
      a history of repeated miscarriages. Therapy evaluation of aspirin and prednisone
      to achieve living term foetus from women in whom antiphospholipid antibodies had
      been detected and who had become pregnant again. PATIENTS AND METHODS: 82
      consecutive women with history of at least of two miscarriages, with no live
      foetus in either case. 14 women positive for antiphospholipid antibodies who had
      become pregnant again (group of therapy evaluation), were treated with aspirin
      (125 mg/d) and prednisone (20 mg/d). 60 normal pregnant women (control group).
      Lupus anticoagulant evaluation: APTT tests caolin clotting time and APTT system
      neutralized with platelet phospholipids. Antiphospholipid antibodies: ELISA test.
      RESULTS: 13.4% were positive to antiphospholipid antibodies (ELISA), and 2.4%
      were positive in both positive in both test. Therapy evaluation: 75.5% (11 cases)
      of pregnancies were successful (normal foetus), 14% (2 cases) of fetal losses,
      and 7% (1 case) of foetal malformations (acranius). CONCLUSIONS: In our study the
      antiphospholipid antibodies represent one of the main causes of repeated foetal
      losses. We recommended in cases of infertile women to test for antiphospholipid
      antibodies regularly. We confirm the effectiveness of the therapy (aspirin and
      prednisone) in achieving successful pregnancies in patients with a history of
      infertility.

PMID- 8553175
TI  - [Multicentric Castleman's disease. Current aspects of pathogenesis and
      treatment].

PMID- 8553174
TI  - [Abnormal autonomic cardiovascular responses in patients with sickle cell
      anemia].
AB  - PURPOSE: To evaluate the presence of anomalies of the autonomic reflex
      cardiovascular response in patients with chronic sickle-cell anaemia. PATIENTS
      AND METHODS: The study was extended to 30 patients with sickle-cell anaemia, 10
      patients with iron-lack anaemia and 30 healthy subjects. Age and sex distribution
      was similar in each group. To be included in the study, patients should have had
      no painful crisis or blood transfusion in the 6 months previous to the assay.
      Clinico-laboratory survey, chest x-ray and EKG were performed in every case.
      Blood cell count and abnormal haemoglobin study on cellulose acetate were carried
      out as well. The evaluation of reflex autonomic responses was performed by means
      of active orthostatism, cold pressor test, Valsalva maneuver and urine
      catecholamine output. The statistical analysis was performed with the variance
      analysis (ANOVA) for multiple groups. RESULTS: The following abnormalities were
      found: 12 patients had haemoglobin SS, 8 had haemoglobin SS and F, 3 had
      haemoglobin SC, 2 had haemoglobin S and beta-thalassaemia, and 5 had combined
      haemoglobin SS,F and A2. Systolic pressure and heart frequency in the supine
      position were similar in all groups. Diastolic pressure was lower in the sickle
      cell anaemia group with respect to the normals. Patients with sickle-cell disease
      had lower heart frequency in the active orthostatism test with regard to the
      other groups, along with paradoxal changes in systolic pressure and lesser
      increase of the diastolic pressure. Significantly lower response to the cold
      pressor test was seen in the sickle-cell patients as compared with the iron-lack
      cases and the normal controls. Reduced sympathetic tachycardia was seen with the
      Valsalva maneuver, whereas the bradycardia was similar to the other groups. The
      urine noradrenaline in output was significantly lower in the sickle-cell
      patients, it was normal in the other groups (p < 0.01). CONCLUSION: These results
      suggest a defective sympathetic activity of heart and arteries in patients with
      sickle-cell anaemia.

PMID- 8553176
TI  - [The actual risk of retrovirus transmission from transfusions].

PMID- 8553177
TI  - [Alfa-2a interferon induces molecular remission in post-BMT relapse of chronic
      myelogenous leukaemia. Report of a case with loss of bcr-abl RNA].
AB  - Alpha-interferon (alpha-IFN) has been used in relapsed CML post-BMT, cytogenetic
      responses being attained in a number of cases (33 to 42%). In first chronic phase
      CML patients such cytogenetic response has been correlated with the disappearance
      of the bcr region rearrangement, as seen with Southern-blot, but when RT-PCR is
      used only a small number of patients maintain undetectable traces of the Ph1
      clone. A case of CML in haematological and cytogenetic relapse after BMT is
      reported who showed criteria of "accelerated" phase and, after treatment with
      alpha-IFN achieved haematologic, cytogenetic and molecular remission (Southern
      blot and PCR negative) and disappearance of the abnormal clone with recovery of
      the donor haemopoiesis. The duration of the alpha-IFN cytogenetic response is
      longer than that of BMT (5 vs 3.5 yr), which is noteworthy. Taking the low
      toxicity of alpha-IFN into account, as compared with that of the other choices (a
      second BMT, IL2), this treatment should be offered to all patients with
      cytogenetic relapse after BMT.

PMID- 8553178
TI  - [Adult HTLV-I positive leukemia-lymphoma in Argentina].
AB  - Human T-cell lymphotropic virus type I (HTLV-I) is associated with adult T-cell
      leukaemia/lymphoma (ATLL) and tropical spastic paraparesis (TSP/HAM) in endemic
      and non-endemic areas. Serological studies have shown that HTLV-I is prevalent in
      some Latin American countries such as Brasil, Chile, Colombia, Peru and Uruguay.
      We describe here the clinical and laboratory features of five cases of ATLL
      diagnosed in Argentina. All patients (4 males, 1 female; median age 48.2 years)
      were of caucasian origin; 4 born in Argentina and 1 in Chile. High risk factors
      for HTLV-I infection were not apparent in Argentina patients, whereas the Chilean
      resident, who was a promiscuous heterosexual, travelled through Chile frequently.
      Positive results for antibodies to HTLV-I were detected in all five cases and in
      some of their relatives. This report suggests that HTLV-I infection may be
      endemic in, Argentina where TSP has also been described.

PMID- 8553179
TI  - [Cytogenetic alterations found by chromosome analysis and fish technique in two
      patients with variant chronic lymphocytic leukemia].
AB  - Chromosomal studies in CLL have yielded poorer results than in other blood
      diseases because of the low mitotic index of the B cells. The FISH technique is a
      very useful tool for trisomy 12 detection in interphase nuclei in CLL, although
      this method cannot be a substitutive for conventional cytogenetics. The FISH
      technique was applied in two cases of CLL by means of satellite DNA probing
      specific for chromosome 12 according to the Oncor S 1370-CF kit protocol. Trisomy
      12 was detected, along with other chromosomal abnormalities secondary to this
      trisomy. Both patients had lymphocyte counts lower than 5.0 x 10(9)/L and their
      peripheral blood immunophenotype showed 58% lymphocytes with lambda sIg of medium
      density, co-expressing CD5 and unable to form rosettes with mouse red-cells.
      Patient no. 1 was 46,XY/47,XY + 12/47,XY + 12,5q-, and patient no. 2 was
      46,XX/47,XX + 12,14q-. The presence of secondary anomalies could explain the
      special clinico-haematological picture, characterised by low lymphocytosis and
      presence of irregular nuclei in mature lymphocytes, along with the lack of CD23
      expression and rosette formation with mouse red-cells. FISH technique combined
      with chromosome analysis may prove a useful means for diagnosing and recognising
      variants or specific entities within low-grade lymphoproliferative syndromes.

PMID- 8553181
TI  - [Evaluation of haematologic analyzer Serono System 9020+ in oncohaematologic
      patients].

PMID- 8553180
TI  - [Cytogenetic abnormalities in seven patients with the Sezary syndrome].
AB  - The cytogenetic studies performed on 7 patients diagnosed of Sezary's syndrome
      are reported. The chromosomal study was made after 72 hours of culture of
      phytohaemagglutinin-stimulated peripheral blood. The 7 patients had abnormal
      karyotypes, the numeral alterations involving chromosomes 10 and 13, whereas the
      structural abnormalities affected chromosomes 1, 2, 4, 6 and 14. The large-cell
      variant has been associated with tetraploidy and the small-cell variant with
      diploidy, but this fact was not confirmed in the present series.

PMID- 8553182
TI  - [Anaemia and macroglossia as the first clinical features of multiple myeloma and
      amyloidosis].

PMID- 8553183
TI  - [IgG multiple myeloma of 13 years of development].

PMID- 8553184
TI  - [Seronegative rheumatoid arthritis and neuropathy as paraneoplastic phenomena in
      a case of chronic myelomonocytic leukemia].

PMID- 8553185
TI  - [Prognostic significance of serum immunoglobulins in chronic lymphocytic
      leukemia].

PMID- 8553186
TI  - [Inefficacy of plasma perfusion in thrombotic thrombocytopenic purpura and early
      relapse after plasmapheresis].

PMID- 8553187
TI  - Parent and professional perceptions about stress and coping strategies during a
      child's lengthy hospitalization.
AB  - The two goals of this study were (1) to describe the stressors and coping
      strategies of families whose children with chronic illness require lengthy
      hospitalizations and (2) to compare family reports of stress and coping
      strategies to professionals perceptions of the same. A non-randomized sample of
      13 families (13 mothers and 5 fathers) whose child with chronic illness was
      hospitalized for a minimum of 30 days and 11 professionals who worked with such
      children were interviewed in a semi-structured survey using open-ended questions.
      Key phrases from family interviews were organized into categories of family
      reported stressors and coping strategies. Key phrases from professional
      interviews were categorized into family stressors and descriptions of challenging
      families. Families and professionals reported that personal emotions and
      communication problems were the most predominant stressors.

PMID- 8553188
TI  - Model for management of services to low income pediatric asthma patients.
AB  - The article describes Project Concern, a unique, managed care program of direct
      assistance for low income, pediatric, asthmatic patients. In cooperation with the
      St. Louis Chapter, Asthma and Allergy Foundation of America, the program was
      developed by a hospital social worker in response to a need for cost-effective,
      coordinated care to a high-risk population. As a result of the success of Project
      Concern, it is suggested that this model be used for other chronic illness where
      there is a lack of resources for patients and families who have specialized
      health care needs.

PMID- 8553189
TI  - Families of young technology-dependent children and the social worker.
AB  - Health care social workers are increasingly providing services to young children
      who are technology-dependent through participation on individualized family
      service plan (IFSP) teams, as well as in clinical settings. Such participation
      suggests that new models for assessing the impact of medical technologies on
      family functioning will, of necessity, also begin to emerge. Assessment
      implications from a family systems perspective are presented that may be used to
      guide the development of future assessment strategies for health care social
      workers.

PMID- 8553190
TI  - Social work in pediatric oncology: a family needs assessment.
AB  - When a child is diagnosed with cancer, the family is confronted with meeting both
      the physical and psychosocial needs of the child and maintaining normal family
      functioning. This study assessed the perceived psychosocial needs of 77 families
      who have a child diagnosed with cancer. Preliminary results suggest practical
      application for social work interventions in specific areas such as the
      development of an informal support network, enhancement of communication within
      families concerning the disease, the need for adequate information at various
      stages of the disease, and continued supportive services for the family.

PMID- 8553191
TI  - Home care for children dependent on medical technology: the family perspective.
AB  - Children who are dependent on medical technology present unique challenges to
      families and professionals who attempt to care for them at home. This
      longitudinal, exploratory study examines the placement threatening crises
      experienced over an eighteen-month period by four such families in Minnesota. The
      findings encourage development of a family support model of placement prevention
      for this population, as opposed to a crisis intervention model.

PMID- 8553192
TI  - Respite care for HIV-affected families.
AB  - Anonymous testing of all newborn infants in 1988 revealed that one of every 61
      babies born in New York City was HIV positive (New York City Department of
      Health, 1988). With the availability of new treatment, HIV positive children are
      living longer, often into their school years, and most are able to live at home.
      The majority of children acquire HIV through maternal transmission. Frequently,
      multiple family members are HIV positive. Parents, or other caregivers, are
      overwhelmed by depression, anxiety and grief, and urgently need childcare
      assistance. Finding childcare is difficult since families are often reluctant to
      disclose the AIDS diagnosis to potential childcare workers. This article
      describes an innovative in-home respite care program for parents and caretakers
      of children who are HIV positive. The service is coordinated through a hospital's
      social work and volunteer departments. This article describes strategies to
      recruit, train and supervise volunteers to provide respite care for families with
      HIV positive children.

PMID- 8553193
TI  - Pediatric critical care social work: clinical practice with parents of critically
      ill children.
AB  - Pediatric critical care settings provide medical care to children who have
      serious, often life-threatening illnesses or injuries. The role of social work in
      this setting has expanded significantly, paralleling advances in medical
      technology. The term "critical care" has often been associated with trauma.
      Today, critical care extends beyond the immediate crisis. Technologic advances
      can prolong life and necessitate ongoing medical interventions. These
      interventions create a more hopeful, although fragile life course. Therefore,
      these developments challenge the social worker to operationalize practice and to
      create new models of intervention.

PMID- 8553194
TI  - A model for group intervention with the chronically ill: cystic fibrosis and the
      family.
AB  - Chronic illness in children creates ongoing stresses for patient and family. As
      the illness progresses and the child passes through various developmental
      milestones, the physical and psychological sequelae must be dealt with. This
      article discusses a psychosocial group intervention program developed at a Cystic
      Fibrosis Center in a children's hospital to maximize adaptive and functional
      responses. It also describes the issues and themes which emerge for patients,
      families and staff as current treatment brings chronically ill children into
      adolescence and young adulthood.

PMID- 8553195
TI  - Families helping families: an innovative approach to the provision of respite
      care for families of children with complex medical needs.
AB  - Over the past thirty years, rapid advances in medical technologies have resulted
      in a marked increase in the numbers of children surviving with significant
      medical and developmental difficulties. The general trend in society away from
      institutional care, in conjunction with these technological advances, has
      resulted in the expectation that parents will provide care at home for children
      with significant disabilities, often in the absence of adequate social service
      supports. This article describes a family support project, Families Helping
      Families, which implemented a cost-effective, family-centered approach to the
      provision of respite care for children with complex medical needs. The paper
      presents the role of the social worker in developing and implementing the
      program. Barriers to more widespread implementation of the model, both in the
      state system and within the medical community, are also described.

PMID- 8553196
TI  - Treatment of adolescent substance abusers: issues for practice and research.
AB  - Treatment of adolescent substance abuse poses difficult challenges to social work
      practitioners. Effective intervention requires awareness of assessment and
      treatment approaches and knowledge of individual, peer, and family factors that
      contribute to alcohol or drug use. Social work's emphasis on contextual factors
      in the etiology and maintenance of addictive disorders is an important
      contribution to substance abuse treatment. Practitioners are in an excellent
      position to implement interventions addressing multiple causes of substance
      abuse. This paper discusses the prevalence of alcohol and drug use among
      adolescents in the United States. Assessment issues are identified and promising
      approaches to treating adolescents with substance use problems are noted.
      Implications for social work practice and research are delineated.

PMID- 8553197
TI  - Review of literature on heart transplant recipients' return to work: predictors
      and outcomes.
AB  - The article reviews research on the rate of return to work of heart transplant
      recipients, examines findings associated with return to work and explores the
      implications of those findings for social work research, practice and policy in
      heart transplantation programs. Findings of studies reviewed in the article
      support the conclusion that there are significant sources of variation in
      recipients' return to work other than surgical outcome. Predictors of return to
      work include pre-transplant factors as well as social structural factors.

PMID- 8553198
TI  - Afro-American women living with HIV infection: special therapeutic interventions
      for a growing population.

PMID- 8553199
TI  - Social work research in hospital settings: strategies for implementation.
AB  - In recent years there has been a growing interest among hospital Social Work
      departments, especially those associated with major medical research institutions
      and universities in initiating research which could inform clinical practice. Yet
      little has been written that describes the process required to develop social
      work research within health care agencies and institutions. In this paper we
      discuss some of the challenges social work departments will confront in
      developing a research program, and alternative solutions that might be considered
      in different institutional settings. We identify ways to: (1) select an effective
      model and develop institutional support for social work research; (2) prepare
      clinical staff for interaction with the research effort; (3) consider relevant
      factors in selecting topics for study; (4) identify personnel required for
      specific research functions; and (5) secure outside funding.

PMID- 8553200
TI  - The effects of managed behavioral health care utilization review on hospital
      substance abuse detoxification.
AB  - Four groups drawn from patients in a hospital substance abuse detoxification unit
      were compared to determine if staff training on the basics of managed care would
      impact the length of the hospital stay authorized by private health insurance
      providers. Pre- and post-intervention groups were drawn from patients carrying
      the most frequently used insurance, Blue Cross/Blue Shield (BC/BS) and from
      patients of all other private insurance providers. Results indicate that the most
      frequently used provider was authorizing lengths of stay consistent with those of
      other private providers. However, results also indicated that significantly
      shorter lengths of stay were being authorized by all of the private insurance
      providers during the post-intervention period of the study. This study (1)
      confirms clinical observations showing a trend toward shorter lengths of hospital
      stays for patients with substance use disorders and (2) confirms that these
      decisions are being made primarily by insurance providers.

PMID- 8553201
TI  - Measurement in social work practice.

PMID- 8553202
TI  - Stressors, social support, and adjustment in kidney transplant patients and their
      spouses.
AB  - Kidney transplant patients and their spouses (n = 121 couples) rated their
      overall stress, social support, and adjustment following transplantation.
      Patients experienced significantly more overall stress than did spouses, although
      spouses were equally or more stressed than patients on some issues. Patients and
      spouses did not differ in marital satisfaction, although patients reported
      significantly more depression than did spouses. Overall stress was related to
      lower marital satisfaction and increased depression for both patients and
      spouses. Patients who were experiencing higher stress benefitted more from the
      support they received from their spouses. Spouses who were less stressed offered
      more helpful and less unhelpful support to patients. Implications for social work
      practice are discussed.

PMID- 8553203
TI  - Peritoneal host defenses are less impaired by laparoscopy than by open operation.
AB  - There is a growing body of evidence that laparoscopic surgery is physiologically
      less injurious than open surgery. We hypothesized that the open technique results
      in a greater impairment of peritoneal and systemic defense mechanisms than does
      the laparoscopic technique. Nissen fundoplication, standardized in technique and
      duration, was performed in 16 pigs. The procedure was performed through a
      standard midline incision (OPEN, n = 8) or with laparoscopic technique and CO2
      pneumoperitoneum (LAP, n = 8). The peritoneal cavity was instilled with 400 cc of
      normal saline, either alone (not contamined, n = 8) or containing 10(9) E.
      coli/ml (contaminated, n = 8). Quantitative cultures, cell count, and flow
      cytometry were performed on blood and peritoneal fluid samples obtained at timed
      intervals. We found that host defense processes were better preserved after LAP
      than by OPEN surgery. Peritoneal and systemic monocyte class II antigen
      expression, and serum tumor necrosis factor-alpha activity was greater in the
      OPEN group compared with the LAP group, but peritoneal bacterial clearance was
      more efficient in the LAP group. These data may illustrate a potential benefit of
      laparoscopic surgery in cases of peritoneal contamination.

PMID- 8553204
TI  - Experimental carbon dioxide pulmonary embolization after vena cava laceration
      under pneumoperitoneum.
AB  - The potential for pulmonary embolization following major venous laceration
      occurring during laparoscopic surgery has never been evaluated. Five anesthetized
      dogs were hemodynamically monitored with an arterial line and Swan-Ganz catheter.
      Observation by transesophageal echocardiography (TEE) allowed comparison with
      pulmonary artery pressure (PAP) recording. Under pneumoperitoneum, a 1-cm
      venotomy was performed in the infrarenal vena cava and a total of 11 events were
      evaluated upon unclamping the venotomy. These results were compared with
      intravenous (i.v.) bolus injections of 15 cc of CO2 (15 events) and of 100 cc of
      CO2 (12 events). The animals were maintained euvolemic. In 2 out of the 11 (18%)
      events which followed unclamping the venotomies, a few CO2 bubbles were seen in
      the right heart cavities. However, the quantity of gas was much less important
      than that seen after i.v. injection of 15 cc and 100 cc of CO2. There was no
      significant elevation of the PAP from pre-event values after venotomy or after
      i.v. injection of 15 cc of CO2. However, there was a significant difference (P <
      0.05) when these results were compared to the PAP values recorded after i.v.
      injection of 100 cc of CO2. No dog died after these episodes of embolization.
      Massive i.v. injection of CO2 (> 300 cc) led to appearance of gas bubbles in the
      left heart cavities and death. This experiment suggests that caution should be
      exerted when laparoscopic surgery is performed beside large veins. Nevertheless,
      the observation that no gas embolism occurred in 82% of the cases after
      unclamping venotomies was unexpected. In contrast, many more gas bubbles were
      detected in the right heart after i.v. injection of only 15 cc of CO2. TEE is a
      more sensitive indicator of pulmonary embolization than elevation of PAP.

PMID- 8553205
TI  - Single-stage laparoscopic treatment of gallstones and common bile duct stones in
      120 unselected, consecutive patients.
AB  - Feasibility, success rate, safety, and short-term results of single-stage,
      laparoscopic, transcystic--whenever possible--or choledochotomic treatment of
      gallstones and common bile duct (CBD) stones were evaluated in 120 unselected
      patients. Of 1095 patients who underwent laparoscopic cholecystectomy, 120 had
      ductal stones; among those patients, stones were suspected or proven in 72, 27 of
      whom were referred after failed endoscopic sphincterotomy (ES) performed
      elsewhere; unsuspected CBD stones were discovered in 48. The procedure was
      successful in 116 patients. Four patients required conversion to open surgery.
      The transcystic access was feasible in 77 patients; a choledochotomy was required
      in 39. Incidence of retained CBD stones was 4.3%. Minor complications, major
      complications, and mortality were observed in 6.8%, 1.7%, and 0.8% of patients,
      respectively. Single-stage laparoscopic treatment of gallstones and CBD stones in
      unselected patients is safe and feasible in the majority of cases, with success
      rates and short-term results that are not inferior to reported results of ERCP/ES
      and cholecystectomy.

PMID- 8553206
TI  - Biliary tract complications of laparoscopic cholecystectomy are detected more
      frequently with routine intraoperative cholangiography.
AB  - Controversy over whether intraoperative cholangiography (IOC) should be done
      routinely has intensified since the advent of laparoscopic cholecystectomy (LC).
      As yet, no study has demonstrated a clear benefit to its use, although their have
      been suggestions in the literature that routine use may confer an advantage to
      detection of injuries. One-hundred seventy-seven biliary tract complications
      occurring secondary to LC were identified from the combined data of seven
      institutions. The goal of this retrospective study was to examine the impact of
      IOC on the occurrence, recognition, and correction of such complications. The
      complications identified include 39 cystic duct leaks, 69 major ductal leaks or
      strictures, and 69 major ductal transection or excision injuries. Whether IOC was
      performed was known in 157 (88%) patients with 53 patients definitely having and
      104 not having an IOC. Data concerning IOC were unavailable in 20 cases. More
      injuries were detected intraoperatively in the group having IOC (P < 0.001).
      Conversion of the LC to a laparotomy, often for repair of the injury, occurred
      more commonly in the group having a correctly interpreted IOC (P < 0.001).
      Conversion resulted in detection of injuries sooner, resulting in fewer operative
      procedures to correct the injury (P < 0.001). A transecting injury was prevented
      in at least seven patients when no visualization of the proximal biliary tree was
      documented by IOC. These partial ductal incisions were treated by t-tube
      placement. Incorrect interpretation of the IOC occurred in at least eight
      patients, with no identification of the proximal biliary tree in six.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8553207
TI  - Immediate laparoscopic cholecystectomy as definitive therapy for acute
      cholecystitis.
AB  - The objective of this study was to determine the safety and efficacy of immediate
      laparoscopic cholecystectomy in the management of acute calculous cholecystitis.
      A prospective data collection was performed on all patients admitted to one
      surgical service over a 2-year period. The patients were managed by a uniform
      protocol consisting of (1) preoperative ERCP when common duct stones were
      suspected; (2) operation within 24 h of diagnosis; and (3) selective operative
      cholangiography. Previous surgery was not a contraindication to inclusion. The
      setting was an urban teaching hospital. There were 52 patients, 34 females and 18
      males. Nineteen had undergone previous abdominal surgery. Five patients had
      preoperative ERCP and five had intraoperative cholangiography. The patients
      underwent laparoscopic cholecystectomy 0.8 +/- 0.4 days postadmission. Four
      (7.7%) were converted to open cholecystectomy. Fifty-eight percent had spillage
      of bile and/or stones. Patients went home 2.3 +/- 1.6 days postoperatively. There
      were no deaths and two complications: a subhepatic biloma and a superficial wound
      infection. Follow-up of all patients has revealed no late complications. We
      conclude: (1) Immediate laparoscopic cholecystectomy is safe and effective for
      acute cholecystitis even when complicated by previous surgery, inflammatory
      adhesions, and gangrene. (2) Intraoperative spillage of bile and stones does not
      lead to an increase in early complications. (3) Cholangiography is needed only
      when clinically indicated. (4) Laparoscopic cholecystectomy should be the
      treatment of choice for patients admitted for acute cholecystitis.

PMID- 8553208
TI  - The impact of previous abdominal surgery on outcome following laparoscopic
      cholecystectomy.
AB  - The first 1000 patients undergoing laparoscopic cholecystectomy (LC) at our
      institution were reviewed to investigate the impact of previous abdominal surgery
      on LC. The 454 patients having no previous abdominal surgery (NS) were compared
      to the 541 patients who had previous surgery (PS). PS patients were older, more
      likely to be female, and had a higher ASA risk category. PS patients had a higher
      incidence of wound infection, but in all other parameters of outcome, including
      operative duration and completion, length of hospitalization, and morbidity,
      there were no significant differences between PS and NS. When PS patients with
      previous upper abdominal surgery (PUAS, n = 59) were separately compared to the
      remainder of the entire patient group (NUAS, n = 936), the PUAS group was found
      to be older, to be more likely to be male, and to have a higher ASA risk
      category. PUAS patients had a longer postoperative hospitalization, and an
      increased incidence of intraoperative, postoperative, and total complications,
      readmissions to the hospital, and unrelated deaths. We conclude previous lower
      abdominal surgery has little impact on the outcome of patients undergoing LC
      while previous upper abdominal surgery is associated with increased morbidity.

PMID- 8553209
TI  - Is endoscopic injection hemostasis of bleeding gastrointestinal ulcers obsolete
      in 1995?
AB  - Bleeding non-neoplastic lesions of the upper gastrointestinal tract, not due to
      portal hypertension, are a frequent cause of emergency admission. In the present
      paper we report our retrospective experience in hemostatic injection treatment of
      these lesions. From May 1990 to May 1994, 164 patients were admitted to our
      institution for a bleeding gastrointestinal lesion. In 124 cases an ulcer
      classified according Forrest's criteria was detected. Four patients underwent
      immediate surgery. The second group of 86 patients (FIIa/FIIb/FIII) were treated
      conservatively. The third group of 34 patients (FIa/FIb/FIIa) underwent
      perilesional injection of adrenaline 1:10,000 and polidocanol 1% saline solution
      during endoscopic examination; 29% (25 pts) of the second group re-bled during
      the first 72 h vs 8.8% (3 pts) of the third group. The postoperative morbidity in
      the rebleeding patients was higher in the second group: 38.4% vs 0%. The
      importance of immediate, inexpensive, and simple hemostatic treatment extended to
      Forrest IIa lesions is emphasized.

PMID- 8553210
TI  - Operative enteroscopy. A useful tool in the evaluation and intervention of
      bilioenteric anastomoses.
AB  - Roux-en-Y hepaticojejunostomy is the procedure of choice in the management of
      patients with major bile duct injuries. In instances of anastomotic stricture,
      this anastomosis is inaccessible to conventional endoscopy. A technique is
      described for assessment and intervention of bilioenteric anastomoses that escape
      the reach of conventional endoscopy. Three cases are presented illustrating the
      feasibility of open and laparoscopic-assisted small-bowel endoscopy. All patients
      presented with recurrent cholangitis and had multiple interventions in their
      biliary tree prior to referral. At operation, the limb of jejunum going to the
      bilioenteric anastomosis was identified, an enterotomy was made, and a flexible
      endoscope was passed to evaluate the anastomosis. In two cases the anastomosis
      was revised by endoscopically excising scar tissue. In the third case the
      anastomosis was patent and unnecessary intervention was avoided. There was no
      morbidity or mortality and the patients had complete resolution of their
      symptoms. Operative endoscopy appears to be useful in the evaluation and
      intervention of bilioenteric anastomoses that cannot be evaluated by conventional
      endoscopy.

PMID- 8553211
TI  - Laparoscopy and major retroperitoneal vascular injuries (MRVI).
AB  - Injury to major retroperitoneal vessels is a potential serious complication of
      laparoscopy occurring when the Veress needle or trocar is inserted. This report
      is a review of major retroperitoneal vascular injuries (MRVI) occurring during
      laparoscopy, as these injuries have not been well documented in the literature. A
      retrospective, observational review of general surgical laparoscopy cases was
      conducted over a 3.5-year period in three community, university-affiliated
      hospitals. We identified 4 MRVI in 3591 laparoscopic procedures. These cases were
      critically analyzed and compared. The incidence of MRVI was approximately 0.1%.
      All cases occurred with the closed (blind) insertion technique of Veress needle
      and primary trocar insertion technique with disposable "safety" shield trocars.
      All patients sustaining MRVI had acute hypotension introperatively and
      significant blood loss necessitating postoperative transfusions. Recognition and
      rapid conversion to laparotomy are keys to enhancing outcome. There is
      significant potential for morbidity and mortality with laparoscopic MRVI,
      although each patient in this series was discharged without obvious short-term
      problems. The advantages of an open approach for primary trocar insertion are
      numerous and should alleviate the risk of MRVI associated with general
      laparoscopic surgery.

PMID- 8553212
TI  - Short-term outcome analysis of a randomized study comparing laparoscopic vs open
      colectomy for colon cancer.
AB  - The authors examined the impact of the laparoscopic approach on the early outcome
      of resected colon carcinomas. The role of laparoscopic techniques in the
      treatment of colon carcinomas is questionable. Previous studies have suggested
      technical feasibility of surgical resections of these cancers by laparoscopic
      means and have implied a benefit to laparoscopic technique for patients
      undergoing colorectal resections. A prospective, randomized study was conducted
      comparing laparoscopic assisted colectomy (LAC) open colectomy (OC) for colon
      cancer. We present the preliminary results in relation to the short-term outcome
      and judge the feasibility of the laparoscopic procedure to as a way of performing
      accurate oncologic resection and staging. Benefit has been demonstrated with LAC
      in this setting. Passing flatus, oral intake, and discharge from hospital
      occurred earlier in LAC- than OC-treated patients. The mean operative time was
      significantly longer in the LAC group than in the OC group. The overall morbidity
      was significantly lower in the LAC group. No significant differences were
      observed between both groups in the number of lymph nodes removed or the
      pathological stage following the Astler-Coller modification of the Dukes
      classification. The laparoscopic approach improves the short-term outcome of
      segmental colectomies for colon cancer. However, the further follow-up of these
      patients will allow us to answer in the near future whether or not the LAC may
      influence the long-term outcome.

PMID- 8553213
TI  - Transanal endoscopic microsurgery in large, sessile adenomas of the rectum. A 10
      year experience.
AB  - The clinical and long-term results of 286 cases encountered from 1983 to 1993 in
      our Department of Surgery regarding the local excision of large, sessile rectal
      adenomas (> 2 cm2) by the endoscopic surgical method and the influence of this
      selected series of adenomas on age, sex, size, grade of dysplasia, and
      architecture are subjects of this study. Histologically proven rectal carcinomas
      as well as non-neoplastic polyps were excluded from this trial. Early
      postoperative complications amounted to 3.4%. The 1-year and 5-year recurrence
      rates +/- SE of adenomas were 1.2 +/- 0.7% and 7.0 +/- 1.9%, respectively.
      Remarkably, there was no significant relationship between the histological type
      of the adenoma and the grade of dysplasia nor between the size and grade of
      dysplasia. However, there was a significant relationship between the size and
      histological type of the adenoma (P < 0.01). With the endoscopic minimal-invasive
      system, we are able to achieve a superior rate of recurrence compared to any
      other local treatment as well as a more favorable operative result compared to
      extensive surgical procedures.

PMID- 8553214
TI  - Can the morbidity of esophagectomy be reduced by the thoracoscopic approach?
AB  - Esophagectomies have a high morbidity rate, mainly related to pulmonary
      complications. The aim of this work was to assess whether the thoracoscopic
      approach could reduce this morbidity. We have made a prospective study of the
      results of 29 attempts of esophagectomy using a right thoracoscopic approach.
      There were 20 males and 9 females having an average age of 47. The indication was
      a squamous cell carcinoma in 22 patients, an adenocarcinoma in 1 patient, a
      melanoma in 1 patient, and a caustic stenosis in 5. The whole esophagus was
      mobilized thoracoscopically and the esophagectomy was completed through the
      abdomen. The reconstruction was achieved using a gastric pull-through and a
      cervical anastomosis. There were five failures for the following reasons:
      unresectable carcinoma (one case), large tumor making a thoracoscopic dissection
      unsafe (two cases), and incomplete lung collapse making the exposure of the
      posterior mediastinum difficult (two cases). The average time of the
      thoracoscopic procedure was 135 min. The postoperative course was uneventful in
      all but five patients who had a pulmonary complication: atelectasis (three
      cases), right purulent pleural effusion (one case), acute respiratory disease
      syndrome (one case). The latter complication was lethal. Four out of five
      respiratory complications occurred in patients for whom the dissection was
      considered difficult. Among the other complications, there were five anastomotic
      leakages and three cases of laryngeal nerve palsy. The mortality rate was 3.8%.
      These initial results do not show a real benefit of the thoracoscopic approach
      for esophageal dissection, especially with respect to difficult esophagectomies.
      Further evaluation of the technique is needed.

PMID- 8553215
TI  - Developing a training model for laparoscopic common bile duct surgery.
AB  - Because of the paucity of adequate training models for laparoscopic common bile
      duct exploration, a live porcine training model was developed and evaluated. This
      model requires preliminary laparoscopic ligation of the distal bile duct 7-14
      days prior to utilization. It aids the development of skills for laparoscopic
      common bile duct exploration and should enhance the subsequent performance of
      these procedures.

PMID- 8553216
TI  - A postgraduate teaching course in laparoscopic surgery.
AB  - A teaching course in laparoscopic surgery was addressed to 21 young postgraduates
      as a part of their general surgery program with the aim of making them familiar
      with the basic principles of laparoscopic surgery. The methodology was based on
      tutorial teaching and "learning by problems"; the students worked in little
      groups elaborating check lists, discussing problems, and practising with
      laparoscopic training devices. Theoretical learning, practical abilities, and
      efficacy of tutorial teaching were investigated at the end of the course: the
      participant's understanding of instrument function, mastering of equipment, and
      solutions to clinical problems were good, as were the efficiency and pleasantness
      of the didactic method. Tutorial teaching seems to be a valid model for basic
      training in laparoscopic surgery in a modern medical education program.

PMID- 8553217
TI  - Laparoscopic repair of acute volvulus in a neonate with malrotation.

PMID- 8553218
TI  - Laparoscopic pericystectomy of liver hydatid cyst.
AB  - The following report describes a patient with a hydatid cyst located in segment V
      of the liver which was managed by laparoscopic pericystectomy performed in
      combination with cholecystectomy. Small hydatid cysts can be removed by the
      laparoscopic technique; meticulous resection, without opening the cyst, is
      involved. Compared to the classical approach by laparotomy, this method is less
      traumatic for the patient, it requires a shorter hospital stay, and it is
      followed by faster recovery.

PMID- 8553219
TI  - Unsuspected choledochal cyst during laparoscopic cholecystectomy.
AB  - Cystic dilation of the extrahepatic bile ducts is rarely encountered during
      elective biliary surgery planned for different indications. We report here on a
      patient with unremarkable preoperative workup and normal intraoperative anatomy
      of the cystic pedicle in whom a type I choledochal cyst containing a large stone
      was detected by the combined use of laparoscopic contact ultrasonography and
      intraoperative cholangiography. This case report highlights the importance of
      intraoperative imaging modalities of the ductal system not only in preventing
      iatrogenic injuries and their related complications, but also in detecting
      unsuspected associated biliary pathology which might significantly change the
      course of surgical intervention.

PMID- 8553220
TI  - Laparoscopic resection of a giant omental cyst.
AB  - Omental and mesenteric cysts are uncommon, requiring surgical intervention when
      symptomatic. A report of a giant primary omental cyst successfully treated
      utilizing minimal-access surgical techniques is presented. The laparoscopic
      approach allowed complete, intact excision of the cyst, while decreasing
      operative morbidity and hospital stay.

PMID- 8553221
TI  - Port-site recurrence following video-assisted thoracoscopic surgery.
AB  - Video-assisted thoracoscopic surgery (VATS) is an established modality in the
      management of pleural diseases. We report a case of port-site recurrence
      following management of malignant pleural effusion in an elderly patient with
      extensive pleural metastasis from adenocarcinoma of the lung. Although her
      shortness of breath was relieved following VAT decortication and talc
      insufflation, at 3 months she was found to have a 2.5-cm subcutaneous nodule at
      the camera port site which on biopsy was confirmed to be metastatic in nature.
      Even though the nodule was asymptomatic and the patient prognosis was not
      affected, it is important that both the surgeon and future patients should be
      aware of this potential complication.

PMID- 8553222
TI  - Gasless laparoscopic esophagomyotomy.
AB  - A case of gasless laparoscopic esophagogastric myotomy for achalasia is
      presented. The technical aspects of the technique as well as the benefits of this
      approach are reviewed.

PMID- 8553223
TI  - Avoiding stoma seeding in head and neck cancer patients.

PMID- 8553224
TI  - A laparoscopic technique for lateral oophoropexy to conserve ovarian function
      prior to abdominopelvic irradiation.

PMID- 8553225
TI  - Perforation of the stomach during laparoscopic Nissen fundoplication in a patient
      on chronic corticosteroid therapy.

PMID- 8553226
TI  - Beyond access. Advanced exposure techniques and organ manipulation in
      endosurgery.

PMID- 8553227
TI  - Effect of extraperitoneal carbon dioxide insufflation on intraoperative blood gas
      and hemodynamic changes.
AB  - Carbon dioxide pneumoperitoneum has been shown to produce respiratory and
      hemodynamic changes due to both CO2 absorption and the effects of increased
      intraperitoneal pressure. We have measured the blood gas, end-tidal CO2, and
      hemodynamic changes produced during extraperitoneal CO2 insufflation (n = 22).
      These have been compared with the changes occurring during CO2 pneumoperitoneum
      (n = 11) under standardized anesthetic conditions. The changes observed during
      pneumoperitoneum were consistent with previous descriptions. There was a median
      rise in arterial pCO2 of 1 kPa over the first 15-20 min, followed by a second
      phase of only gradual change. There was also an increase in mean arterial
      pressure of 18 mmHg during the insufflation period. We have found a similar
      magnitude of rise in arterial pCO2 during extraperitoneal insufflation (median
      0.83 kPa), but the rate of rise was significantly slower (P < 0.05). In addition,
      there was no change in the mean arterial pressure during extraperitoneal
      insufflation. Our results suggest that extraperitoneal CO2 insufflation may be
      safer than CO2 pneumoperitoneum in patients with preexisting cardiorespiratory
      disease.

PMID- 8553228
TI  - Hemodynamic and arterial blood gas changes during carbon dioxide and helium
      pneumoperitoneum in pigs.
AB  - The effects of pneumoperitoneum with carbon dioxide and helium on systemic
      hemodynamics and arterial blood gases were investigated in pigs in an attempt to
      clarify the mechanisms by which pneumoperitoneum may induce organ dysfunction. A
      total of 16 anesthetized female pigs underwent pneumoperitoneum with carbon
      dioxide or helium (n = 8 each) in a stepwise fashion to intraabdominal pressures
      of 8, 10, 12, 16, and 20 mmHg. Changes in cardiac output; renal and hepatic blood
      flow; mean arterial, mean pulmonary arterial, mean pulmonary arterial wedge,
      inferior vena caval, and portal venous pressures; and total peripheral resistance
      were measured. Arterial blood samples were obtained at the same time the above
      parameters were determined. Urine volume was measured as an indicator of renal
      function. Pneumoperitoneum with either carbon dioxide or helium significantly
      increased venous pressures and simultaneously decreased cardiac output. These
      changes were associated with decreases in organ blood flow due to increased
      peripheral resistance. Urinary output was reduced to a similar degree in the two
      groups. Blood gas analysis revealed pneumoperitoneum-induced metabolic acidosis
      in both groups, although hypercapnia was observed only in the carbon dioxide
      group. These findings suggest that pneumoperitoneum-related organ dysfunction may
      be due to increased intraperitoneal pressure rather than to hypercapnia.

PMID- 8553229
TI  - Laparoscopic-assisted colectomy. The learning curve.
AB  - One hundred fifty consecutive laparoscopic-assisted colectomies performed by a
      surgical team were analyzed in an attempt to define a learning curve. These
      colectomies performed by the Norfolk Surgical Group over a 24-month period, were
      divided chronologically into six groups of 25 patients each. The groups were then
      compared to determine if any improvement in length of procedure, complication
      rate, conversion rate, or length of stay developed as experience increased. Colon
      cancer and diverticular disease were the most common indications for surgery in
      all groups. Right hemicolectomy, left colectomy, and low anterior resection
      accounted for the majority of procedures in all groups. A significant decrease in
      mean operative time, from 250 min to 156 min over the first 35-50 cases was
      observed before leveling off at approximately 140 min for the remaining group.
      Intraoperative complications were low in all groups (range zero to two) and did
      not show any trend. There was no statistically significant difference in the
      conversion rate (23.3% overall) among the six groups. Length of stay decreased
      from 6 days in the first two groups to 5 days in the last four groups, although
      the difference was not statistically significant. The learning curve for
      laparoscopic-assisted colectomies is longer than appreciated by many surgeons,
      requiring as many as 35-50 procedures to decrease operative time to baseline.
      Complications can be kept at an acceptably low level while on the curve if a
      cautious approach is taken and the surgeon realizes that a prolonged operative
      time is not only acceptable, but appropriate during this long learning process. A
      conversion rate of 20-25% at any phase of the learning process may in fact
      represent a limitation of current technology. When combined with a low
      complication rate it may be the sign of a careful surgeon.

PMID- 8553230
TI  - Video-assisted thoracoscopic management of anterior mediastinal masses.
      Preliminary experience and results.
AB  - The author reports his personal experience on the management of anterior
      mediastinal masses using video-assisted thoracoscopic surgery (VATS) at a single
      institution. From August 1993 to March 1995, 24 patients (14 males and 10 females
      ranging in age from 9 to 76 years old) with anterior mediastinal masses were
      diagnosed or treated by VATS. This consisted of 11 biopsies and 13 resections (11
      thymectomies and 2 thymic cystectomies). Seven biopsies were performed for
      primary histological diagnosis (four non-Hodgkin's lymphoma, two metastatic
      carcinoma, one yolk sac tumor) and four biopsies were performed to detect
      residual tumors following chemotherapy. Complete thymectomy was accomplished in
      all 11 cases by examination of the thymic bed and resected specimen. We have
      reserved this approach for resection of benign masses only. Adequate biopsy for
      histological diagnosis was obtained in all 11 cases to guide further management.
      There was no surgical mortality or intraoperative complications. The median
      postoperative hospital stay for the entire group was 3 days. We conclude that
      VATS for resection or biopsy of an anterior mediastinal mass is technically
      feasible and provides an alternative to the conventional approaches in selected
      patients.

PMID- 8553231
TI  - Laparoscopic preperitoneal colposuspension for stress incontinence in women.
      Technique and results of 37 procedures.
AB  - We present an original laparoscopic technique for treatment of stress urinary
      incontinence in women equivalent to the classical open approach described by
      Burch. This technique is particularly interesting because a wide pneumoretzius
      allows adequate access without being hindered by intestinal loops or the free
      border of the bladder. Suspension is achieved with nonabsorbable mesh bands
      stapled to the vagina and Cooper's ligaments. Seventy nine operations were
      performed at the Department of Gynecology of the University Hospital of Caen,
      France, between 1992 and 1995. The cure rate of the first 37 procedures (with a
      18-42-month-long follow-up) is 86%. Of the patients, 22% had low closure pressure
      and 19% had an unstable bladder. No laparotomy had to be performed.

PMID- 8553232
TI  - Endoscopic ultrasonography in the study of extramucosal swellings in the upper
      digestive tract.
AB  - The authors performed an echoendoscopic examination of 91 patients who, at a
      previous endoscopy, had presented extramucosal swellings in the upper digestive
      tract. On this occasion, the images were suggestive of a leiomyoma in 73 cases, a
      schwannoma in 3, an ectopic pancreas in 1, and a cyst of the gastric wall in 1.
      There was an extrinsic compression of the tract by an adjacent organ in three
      cases and by an adenopathy in two others. In six patients the authors were unable
      to make an echographic identification of the swellings noted upon endoscopy as
      they noted no echographic alteration. The echoendoscopic examination was
      considered normal. Given that most of these patients did not undergo surgery, the
      authors were only able to obtain a histological examination of surgically removed
      tissue in 11. The diagnosis was confirmed in eight cases. In one patient in which
      it proved impossible to pass the endoscope through the stenotic area, the
      histological examination did not confirm the echography: In two others,
      classified as leiomyomas, the histology showed leiomyosarcomas.

PMID- 8553233
TI  - Laparoscopic Thal fundoplication in severely scoliotic children.
AB  - Surgical treatment of gastroesophageal reflux in severely scoliotic children can
      be quite bothersome because sometimes the working space between the subcostal
      margins, iliac crest, and spinal column is very limited; the hiatus lies
      extremely deep away and is frequently rotated, making exposure more difficult.
      The laparoscopic approach could lend the necessary extension to the surgeons'
      hands to reach the deep hiatus. Moreover the entrance of the ports can be
      adjusted to the special requirements dictated by the scoliosis. Between February
      and December 1994 laparoscopic Thal fundoplication was performed in five severely
      scoliotic children; four also had a feeding gastrostomy. There were no
      intraoperative complications. The laparoscopic approach allowed improved
      operative visibility. Mean hospital stay was 3 days. The children displayed no
      symptomatic postoperative gastroesophageal reflux, which was confirmed by 3
      months postoperative pH study. The laparoscopic approach of fundoplication allows
      improved visibility and easier access to the hiatus in severely scoliotic
      patients in comparison to the open approach. Results so far are good.

PMID- 8553234
TI  - Discovery of early gastric remnant carcinoma. Results of a 14-year endoscopic
      screening program.
AB  - Partial gastrectomy for benign ulcer disease has been associated with an
      increased incidence of mucosal dysplasia and invasive adenocarcinoma,
      particularly in patients who are 15-20 years postresection. Using a planned
      protocol of routine endoscopic surveillance with biopsy, 163 patients who were at
      least 10 years postgastrectomy for benign ulcer disease have undergone screening
      flexible esophagogastroduodenoscopy (EGD) between July 1980 and August 1994. The
      completed study group consists of 153 patients who have been examined at least
      yearly over the 14-year period of surveillance. Routine biopsies from various
      areas of the gastric remnant have been interpreted for dysplasia or early gastric
      adenocarcinoma. Patients who evidenced significant dysplasia or adenocarcinoma
      were offered complete gastrectomy during the study. Results of this ongoing 14
      year screening program revealed severe dysplasia of the gastric remnant in 13
      patients (8.4%) with eventual findings of adenocarcinoma in seven of this group
      (54%). These seven patients underwent total gastrectomy with findings of limited
      disease. Six patients continue to be followed with evidence of dysplasia. During
      this 14-year screening program, seven patients undergoing completion gastrectomy
      for early gastric remnant adenocarcinoma continue to be well and free of disease.
      This aggressive screening program supports the concept that neoplastic change in
      the gastric remnant is a function of time from the initial gastric resection.
      Patients identified with early gastric remnant carcinoma benefit by completion
      gastrectomy. In addition, patients harboring dysplasia in the gastric remnant
      should continue to be followed in an aggressive screening protocol utilizing
      random biopsy.

PMID- 8553235
TI  - Thoracoscopic plication of the diaphragm.
AB  - Plication of the diaphragm in symptomatic patients with phrenic nerve paralysis
      provides excellent relief of excertional dyspnea and significantly increases
      arterial oxygen tension, and all lung volumes except residual volume. We report
      diaphragmatic plication using the minimally invasive technique of VATS. This
      procedure provides excellent relief of symptoms with minimal morbidity and short
      hospitalization.

PMID- 8553236
TI  - Unexpected gallbladder cancer and laparoscopic surgery.
AB  - Case histories of three patients who underwent laparoscopic cholecystectomy for
      unexpected gallbladder cancer are reviewed. Port-site recurrence was observed in
      two of them. In one patient whose abdominal wall recurrent tumor was excised, a
      new recurrence developed, but after the reexcision she is symptom-free 10 months
      after the last procedure. The surgeon has to be aware of the fact that the
      survival rate can be doubled in stage pT2 if cholecystectomy is followed by
      extended radical operation. Only gallbladder cancer in stage pT1 does not need
      further procedure, except for excision of port sites. In case of uncertain
      diagnosis preoperative frozen section is recommended. Port-site recurrence does
      not mean an incurable stage of the disease or a sign of diffuse metastases. Even
      after reexcision of abdominal wall metastasis patients might be free from other
      detectable recurrences.

PMID- 8553237
TI  - Surgical endoscopy--outcomes and costs. Introduction.

PMID- 8553238
TI  - Outcomes in medical care--what are they?

PMID- 8553239
TI  - Prospective randomized trials in clinical research.

PMID- 8553240
TI  - Utilization analysis and physician profiling--new paradigm, old paradigm.

PMID- 8553241
TI  - Cost-effectiveness of laparoscopic and mini-cholecystectomy in a prospective
      randomized trial.

PMID- 8553242
TI  - Laparoscopic cholecystectomy. The Maryland experience.

PMID- 8553243
TI  - Laparoscopic cholecystectomy. The Mississippi experience.

PMID- 8553244
TI  - Laparoscopic cholecystectomy in Australia--outcomes and costs.

PMID- 8553245
TI  - ERCP after laparoscopic cholecystectomy.

PMID- 8553246
TI  - Laparoscopic transcystic duct common bile duct exploration--outcome and costs.

PMID- 8553247
TI  - CBD stones--outcomes and costs. Laparoscopic transcystic techniques other than
      choledochoscopy.

PMID- 8553248
TI  - Static cholangiography vs digital fluoroscopy. Intraoperative cholangiography:
      benefit and cost ratio.

PMID- 8553249
TI  - Evaluation of endoscopy in the treatment of rare meningoceles: preliminary
      results.
AB  - BACKGROUND: Endoscopy is used on different occasions-for instance, to open the
      floor of the third ventricule in triventricular hydrocephalus, to open a cyst
      into the cerebrospinal fluid circulation, for biopsy or for partial resection of
      some tumors, or to insert a shunt in hydrocephalus or syringohydromyelia.
      However, the use of endoscopes for evaluating and treating meningoceles remains
      to be assessed. METHODS: Five different kinds of rare meningoceles are presented.
      In each, neuroendoscopy was used as the main tool for exploration and treatment.
      RESULTS: Two sacral meningoceles and one oral cephalocele were cured through a
      keyhole opening under endoscopic control. One posterior sacral meningocele was
      explored and no communication with normal subarachnoid spaces was observed,
      allowing a simple suture of the posterior to the anterior walls. And, last, a
      complex case with three intrasacral meningocles was explored and partially
      treated. CONCLUSIONS: Meningocles with very small communication within the normal
      subarachnoid spaces appeared the most suitable to be cured by an endoscopic
      procedure. In case of a larger communication, the meningocele could be treated,
      or at least the morphology can be better understood, by using a keyhole procedure
      under endoscopic control. In all cases the surgery was of short duration (less
      than 1 hour) and very well tolerated.

PMID- 8553250
TI  - Assessment of delayed cerebral vasospasm using intracisternal echography-
      technical note.
AB  - BACKGROUND: A new technique using intravascular ultrasound has been used for
      diagnosis of coronary artery in order to obtain intravascular echo images. In
      this study, an intracisternally positioned ultrasound catheter was introduced
      obtaining serial echo images of the first segment (MI) of the middle cerebral
      artery in order to detect cerebral vasospasm following subarachnoid hemorrhage
      (SAH). METHODS: Thirteen patients were admitted to Osaka Neurological Institute
      with SAH due to ruptured intracranial aneurysm. All patients underwent surgical
      neck clipping on the day of admission. In each patient, an 8 Fr. ultrasound
      imaging catheter (Cardiovascular Imaging Systems, Inc. (CVIS), Sunnyvale, CA) was
      detained intracisternally adjacent to the M1 segment following neck clipping of
      the aneurysm and placement of cisternal drainage(s) in the prepontine and/or
      distal portion of the Sylvian fissure. In order to detain the mirro device near
      the M1 segment, the tip of a 2.0 cm cisternal drainage tube (SILASCON, E-3L-12,
      Kaneka Medix Co, Osaka, Japan) was attached to the tip of the intravascular
      ultrasound catheter with 3-0 silk suture. The tip was placed in the prechiasmal
      cistern. RESULTS: Angiographic evidence of delayed vasospasm was obtained for
      three (23.1%) of the 13 patients. In one (33.3%) of the three patients who had
      angiographic evidence of vasospasm (25% stenosis), decrease in the inner diameter
      of the M1 segment was detected on the echo images, but in the other two (66.7%),
      no such decrease was noted on echo images. Angiographically identified vasospasm
      in the latter patients was associated with only 10% stenosis. CONCLUSIONS:
      Intracisternally positioned ultrasound catheter can be used for intermittent
      measurement of the diameter of a target artery for detection of cerebral
      vasospasm after SAH.

PMID- 8553251
TI  - Persistent feeding arteries to angiographically completely embolized
      arteriovenous malformation demonstrated by intraoperative color-flow Doppler
      testing: report of two cases.
AB  - Two cases of arteriovenous malformation (AVM) treated preoperatively by
      endovascular embolization that appeared to be completely occluded after
      embolization are presented. Seven and 12 days later, respectively, these patients
      underwent resection of their AVM. At the time of surgery, intraoperative color
      flow Doppler studies revealed persistent feeding arteries to an active residual
      nidus of the AVM. The significance of this finding is presented in light of
      previous published literature.

PMID- 8553252
TI  - Transcranial Doppler analysis of cerebral hemodynamics in primary
      craniosynostosis: study in progress.
AB  - BACKGROUND: Regional elevations in intracranial pressure (ICP) have been
      monitored adjacent to areas of cranial stenosis by some authors [9,19,20];
      however, noninvasive techniques such as transcranial Doppler (TCD) would be
      preferable if increased ICP could be detected just as reliably. METHODS: TCD
      examinations of basal cerebral arteries were performed in 31 children with skull
      deformities. Skull X rays and computed tomography (CT) scans or magnetic
      resonance imaging (MRI) were analyzed for degree of cranial vault abnormality, as
      well as for presence or absence of intracranial pathology. Neurodevelopmental
      examination and clinical signs of increased ICP, if any, were recorded. RESULTS:
      The overall incidence of increased resistivity indices (RI) was 70%. Patients
      with asymmetric skull deformities (plagiocephaly) or sagittal synostosis
      (scaphocephaly) were statistically more prone to exhibit increased RI compared to
      previously reported prevalences. CONCLUSIONS: Because TCD is a convenient, rapid,
      accurate, and noninvasive method by which to gauge ICP, it should be considered
      in the preliminary work-up of a patient with craniosynostosis.

PMID- 8553253
TI  - 99mTc-HMPAO labeled leukocyte SPECT in intracranial lesions.
AB  - BACKGROUND: Scintigraphy with 111In (indium-111)-oxine or 99mTechnetium
      hexamethylpropyleneamine oxime (99mTc-HMPAO) labeled leukocytes has been used to
      differentiate brain abscess from brain tumor. However, there are false positive
      or false negative results from planar scintigraphic images. So a more specific
      and sensitive scintigraphic technique needs to be developed. METHODS: Planar and
      single photon emission computed tomography (SPECT) images were obtained and
      reviewed in 14 patients with intracerebral ring-enhancing lesions on computed
      tomography (CT) or magnetic resonance imaging (MRI). In all patients, diagnosis
      was confirmed by histopathologic examination. The effect of steroids or
      antibiotics on scintigraphic finding was examined. RESULTS: Abscess was confirmed
      in six patients, tumor in six, tuberculoma and cysticercosis in one each,
      respectively. In all the patients with abscess, SPECT showed increased focal
      activity irrespective of steroid or antibiotic therapy. Increased radioactivity,
      which could not be detected on planar images, could be identified in two patients
      with abscess. In three of the six patients with tumor, radiolabeled leukocytes
      did not accumulate in the tumor. In the other three patients with tumor, SPECT
      showed focally increased activity that was less intense than the activity shown
      in the patients with abscess. CONCLUSIONS: 99mTc-HMPAO labeled leukocyte SPECT is
      useful for the differential diagnosis of intracerebral ring-enhancing lesions,
      and the use of steroids or antibiotics does not influence the sensitivity of
      SPECT. Diagnostic sensitivity of scintigraphy with labeled leukocytes could be
      improved by SPECT in addition to planar image.

PMID- 8553254
TI  - Middle cerebral artery endarterectomy: experience with two cases.
AB  - BACKGROUND: Atherosclerotic stenosis of the middle cerebral artery (MCA) is
      uncommon and long-term prognosis is not well defined. Methods of treating
      stenosis of the MCA range from the administration of anticoagulants to
      endarterectomy. METHODS: We present two cases of patients with focal symptomatic
      stenosis of the MCA with evidence of focally decreased cerebral blood flow and
      compromise of cerebral blood flow reserves on xenon-enhanced computed tomography
      (Xe CT) scanning. Endarterectomies were performed after unsuccessful
      anticoagulation therapy. RESULTS: Both patients underwent successful
      endarterectomies of the MCA. Improvement in cerebral blood flow postoperatively
      was documented for both patients. At last follow-up neither patient had
      demonstrated any additional ischemic episodes. CONCLUSIONS: Atherosclerotic
      stenosis of the MCA may be responsible for distal emboli and compromised
      hemodynamics, and endarterectomy of this vessel may provide definitive therapy.

PMID- 8553255
TI  - Rapid spontaneous diminution of cisternal blood on computed tomography in
      patients with subarachnoid hemorrhage.
AB  - BACKGROUND: The purpose of this study is to investigate whether rapid spontaneous
      diminution of cisternal subarachnoid hemorrhage (SAH) alleviates vasospasm in the
      corresponding arterial territory. METHODS: The subjects were 103 patients in whom
      initial computed tomography scans were performed within 24 hours after SAH and
      repeated within 72 hours. We analyzed the effect of diminution of cisternal SAH
      on vasospasm in 16 sites in each patient. Of the total 1642 cisterns. SAH was
      found in 1362 (83%), of which 539 (40%) had a decrease in SAH. The highest
      diminution rate was 64% in quadrigeminal cistern, and the lowest rate was 27% in
      frontal interhemispheric fissure (IHF). In basal frontal IHF, both the incidence
      of diminution of SAH and its degree were significantly lower in patients with
      ruptured anterior cerebral artery aneurysms than in those with other site
      aneurysms, while in suprasellar cisterns, sylvian stems, and sylvian fissures,
      diminution of SAH was not affected by the side of ruptured aneurysms. The
      diminution of SAH in basal frontal IHF and sylvian stems was associated with less
      vasospasm in adjacent arteries. CONCLUSIONS: We concluded that in patients with
      SAH, rapid spontaneous diminution of cisternal blood, which is affected by
      several factors, makes vasospasm in the corresponding arterial territory less
      likely.

PMID- 8553256
TI  - Surgical obliteration for vein of Galen malformation: a case report.
AB  - BACKGROUND: Vein of Galen aneurysm is a relatively rare vascular malformation,
      often resulting in high morbidity or mortality. Outcome is particularly poor in
      the neonatal population. METHODS: We report staged surgical treatment of a vein
      of Galen aneurysm in a neonate who presented in congestive heart failure.
      RESULTS: Cerebral angiography 6 months following staged surgical treatment
      revealed complete obliteration of the aneurysm. The patient tolerated surgery
      well, and at 6 years of age is free of neurologic or cardiovascular impairment.
      CONCLUSIONS: While the endovascular approach is the procedure of first choice,
      aggressive medical management followed by staged surgical clipping of aneurysm
      feeders produced excellent results in this case of neonatal vein of Galen
      aneurysm. Staged surgical obliteration of arterial feeders should be considered
      as a therapy when endovascular methods are unsuccessful in safely curing these
      difficult vascular lesions.

PMID- 8553257
TI  - What's new in pediatric neurosurgery.
AB  - During the past year, there have been some significant papers dealing with
      pediatric neurosurgical problems. These papers deal with arteriovenous
      malformations, spinal cord injury, brain tumors and hydrocephalus. The papers are
      summarized in the following review.

PMID- 8553258
TI  - Clinical significance of admission hyperglycemia and factors related to it in
      patients with acute severe head injury.
AB  - BACKGROUND: Patients in the acute stage after a severe head injury often exhibit
      systemic stress responses. The aim of the present study is to assess in such
      patients the clinical significance of the change of catecholamines (CA) and of
      blood glucose. METHODS: The levels of serum of norepinephrine (NE), epinephrine
      (E), and dopamine (DA) were measured in 48 adults in the first 7 days after a
      severe head injury, and in 35 normal adults as a control group. The blood level
      of glucose at the time of admission was also measured. RESULTS: It was found
      that: (1) The serum CA level was significantly higher in the injured group than
      in controls. (2) The serum NE and E levels were higher in patients with lower
      Glasgow Coma Scores (GCS) and in the group of patients who did not survive. (3)
      The blood glucose level on admission was related both to the serum NE and E
      levels within the first 24 hours after head injury (r = 0.574, p < 0.05 and r =
      0.410 and p < 0.05, respectively) and also the GCS and Glasgow Outcome Score
      (GOS) in these patients. (4) Patients with GCS of 3-4, 5-6, and 7-8 had mean
      glucose levels on admission of 12.805 +/- 3.205 mmol/L (228 +/- 67.23 mg/100 mL),
      9.133 +/- 1.228 mmol/L, (160 +/- 12.28 mg/100 mL) and 6.029 +/- 1.228 mmol/L
      (107.66 +/- 21.9 mg/100 mL), respectively (p < 0.01). (5) Ninety percent of the
      patients with blood glucose levels of 9.6 mmol/L (171.4 mg/100 mL) at admission
      died within the first month; in the patients with lower glucose levels the
      mortality was 15%. CONCLUSIONS: These findings suggest that in the acute stage of
      severe head injury hyperglycemia and elevation of serum levels of CA are common
      components of the stress response, significant indicators of severity, and
      significant predictors of outcome.

PMID- 8553259
TI  - Central nervous system tuberculosis: medical management and surgical indications.
AB  - BACKGROUND: An increase in the incidence of tuberculosis in industrialized
      nations has prompted a need for earlier diagnosis, treatment, and isolation of
      disease. An associated rise in the number of patients with central nervous system
      tuberculosis (CNS TB) has forced neurosurgical services to reevaluate the
      indications for operative intervention. METHODS: Seventeen cases of CNS TB were
      found in a retrospective review of all cases managed on the neurosurgical service
      between 1989 and 1994. These cases included eight with tuberculous meningitis,
      seven cases of supratentorial tuberculomas, and two cases of infratentorial
      tuberculomas. RESULTS: Major permanent neurologic morbidity was seen in one case
      (6%). Five patients (29.4%) died of complications associated with their primary
      disease. Eleven patients (64.6%) had excellent outcomes. All patients in the
      latter group completed an 18-month course of antituberculous therapy.
      Cerebrospinal fluid shunts were necessary in three cases and emergent craniotomy
      was performed in three cases. Only four cases had human immunodeficiency virus
      (HIV) coinfection. CONCLUSION: The neurosurgeon's role in the management of CNS
      TB has once again become more evident. In the present series it is unclear as to
      whether this is due to multiple drug-resistant strains of Mycobacterium
      tuberculosis or HIV coinfection. It is clear, however, that vigilance over
      patient compliance and serial neurologic evaluation will determine the need for
      operative intervention.

PMID- 8553260
TI  - Nonresective treatment of pineoblastoma: a case report.
AB  - BACKGROUND: Stereotactic biopsy followed by cytoreductive surgery and/or
      radiation are the standard treatment for pineoblastoma. We are reporting a
      patient with a relatively large pineoblastoma, who was treated with a combination
      of nonresective treatment modalities. METHOD: The patient is a 20-year-old woman
      who presented with signs and symptoms of raised intracranial pressure. Magnetic
      resonance imaging (MRI) showed a large tumor in the pineal region and
      hydrocephalus. She was emergently treated by placement of a ventriculoperitoneal
      shunt. Three days later she underwent a stereotactic biopsy, which showed the
      tumor to be pineoblastoma. She was then further treated with the following
      treatment modalities: permanent implantation of high activity I125 seeds,
      external radiation, and chemotherapy. RESULTS: At 10 months' follow-up, MRI
      showed complete disappearance of the tumor. At 18 months' follow-up, the patient
      is asymptomatic, neurologically intact, and her MRI scans show no evidence of
      intracranial or intraspinal tumor. CONCLUSIONS: Though the follow-up is
      relatively short, the results of the nonresective approach in this patient have
      been excellent.

PMID- 8553261
TI  - Microsurgical anatomy of the atlantal part of the vertebral artery.
AB  - BACKGROUND: Microanatomy of the vertebral artery has been the subject of multiple
      studies. However, none of them has covered every aspect of microvascular anatomy
      of the atlantal part of the vertebral artery. MATERIALS AND METHODS:
      Microsurgical anatomy of the atlantal part of the vertebral artery was studied in
      14 cadaveric specimens. The artery was dissected using the standard microsurgical
      technique under operative microscope magnification. The atlantal part of the
      vertebral artery was divided into five segments: the foraminal, sagittal,
      transverse, medial condylar, and dural. The length of each segment was measured,
      as was the diameter of the artery. The branches of this part of the artery were
      identified and the distance between the point of dural entry of the artery and
      the midline of the atlanto-occipital dura was measured. Distance between the
      mastoid tip and the artery and the distance between the mastoid tip and the tip
      of C1 transverse process were measured. RESULTS: Results of all measurements are
      summarized in tables and text. We discuss various anomalies, branches, and
      lesions of the vertebral artery and surgical approaches with new methods of
      managing diseases in this area.

PMID- 8553262
TI  - The development of a successful neurosurgical practice.

PMID- 8553263
TI  - Who is going to find out?

PMID- 8553264
TI  - Lung disease induced by drug addiction.

PMID- 8553265
TI  - Nosocomial pneumonia during mechanical ventilation: problems with diagnostic
      criteria.

PMID- 8553266
TI  - Measurement of respiratory muscle strength.

PMID- 8553267
TI  - Induction of macrophage inflammatory protein 2 gene expression by interleukin 1
      beta in rat lung.
AB  - BACKGROUND: Recruitment of inflammatory cells in the lungs may contribute to
      tissue injury as a result of mediators released from these cells. Interleukin 1
      beta (IL-1 beta) is a potent inducer of neutrophil accumulation, a process that
      may require local protein biosynthesis. Macrophage inflammatory protein 2 (MIP-2)
      is a approximately 6 kD heparin binding protein and is a member of the C-X-C
      superfamily that causes significant neutrophil chemotaxis and activation in
      vitro. A study was performed to determine whether IL-1 beta could induce the
      expression of MIP-2 in the lungs of Brown-Norway rats. METHODS: rhIL-1 beta (500
      U) or 0.9% NaCl was injected intratracheally and bronchoalveolar lavage (BAL)
      cells and lung tissues were evaluated for MIP-2 mRNA expression after RNA
      extraction by Northern blot analysis. MIP-2 probe was prepared from cDNA obtained
      by reverse transcriptase-polymerase chain reaction (RT-PCR) of BAL cells obtained
      from a rat treated with lipopolysaccharide. RESULTS: There was no detectable MIP
      2 mRNA in the lungs of control rats but a marked enhancement of the expression at
      four hours with no expression at 12 hours and a slight expression at 24 hours. IL
      1 beta induced a significant influx of neutrophils into BAL fluid with a
      transient increase in macrophages. In situ hybridisation of lungs using MIP-2
      cDNA probe labelled with digoxigenin showed expression of MIP-2 mRNA in airway
      mononuclear cells and airway epithelium at four hours after IL-1 beta; at 24
      hours the signal had nearly gone. CONCLUSION: IL-1 beta induces the expression of
      MIP-2 mRNA in rat lung. MIP-2 may be one chemokine that could contribute to IL-1
      beta induced neutrophil influx.

PMID- 8553268
TI  - Interstitial pneumonitis in patients infected with the human immunodeficiency
      virus.
AB  - BACKGROUND: A study was performed to identify the clinical, radiographic, and
      histopathological features of interstitial pneumonitis in patients infected with
      the human immunodeficiency virus. METHODS: A retrospective review was made of the
      case notes, chest radiographs, and histopathological results of seven HIV-1
      antibody positive patients with symptomatic diffuse pulmonary disease and a
      pathological diagnosis of non-specific interstitial pneumonitis. RESULTS: All
      patients had dyspnoea, with or without cough, and chest radiographs showing
      diffuse infiltrates. The arterial oxygen tension ranged widely from 5.9 to 13.1
      kPa. The initial clinical diagnosis was Pneumocystis carinii pneumonia in most
      cases. The pathological diagnosis was made by transbronchial biopsy in one case
      and by open lung biopsy in six cases. The interstitial pneumonitis consisted of a
      patchy lymphocytic infiltrate composed of B cells in focal aggregates and T cells
      in a more diffuse distribution. The T cell population was a mixture of CD4+ and
      CD8+ cells. The histological findings contrast with the more extensive infiltrate
      of predominantly CD8+ lymphocytes seen in HIV-associated lymphocytic interstitial
      pneumonitis which occurs mainly in children. The condition ran a subacute course.
      Three patients spontaneously improved and three improved with steroid therapy.
      Long term survival was less than three years, the prognosis being determined by
      other infective or neoplastic complications. CONCLUSIONS: Non-specific
      interstitial pneumonitis usually presents with an illness resembling Pneumocystis
      carinii pneumonia but occurs when the CD4 and total lymphocyte counts are still
      preserved. The pneumonitis resolves spontaneously or responds to steroids, and
      does not itself lead directly to the patient's death. It does, however, appear to
      mark a downturn in the course of HIV infection.

PMID- 8553269
TI  - Mycobacterial infection in HIV seropositive and seronegative populations, 1987
      93.
AB  - BACKGROUND: Although the causes of the worldwide resurgence of tuberculosis are
      multifactorial, the HIV epidemic is believed to have had a central role. Control
      is further threatened by the emergence of multidrug-resistant tuberculosis.
      METHODS: A retrospective evaluation was undertaken of trends in pulmonary and
      extrapulmonary culture positive mycobacterial pathology, and the prevalence of
      drug-resistant tuberculosis in both HIV seropositive and, presumptively, HIV
      seronegative patients receiving their clinical care at St Mary's Hospital,
      London. Five hundred and thirty eight patients (188 of whom were known to be HIV
      seropositive) with positive mycobacterial isolates between January 1987 and March
      1993 were identified from laboratory records. These were cross referenced with
      drug surveillance records. RESULTS: Overall, between 1987 and 1992 there was a
      progressive 3.5 fold increase in positive mycobacterial isolates and a 2.5 fold
      increase in patients with proven mycobacterial infection. This increase was
      greater within the HIV seropositive population. A total of 663 positive
      mycobacterial isolates was evaluated; the major pathogen identified was
      Mycobacterium tuberculosis (379 isolates, 57%). Three hundred and fourteen
      patients were diagnosed as having M tuberculosis, 49 of whom were HIV
      seropositive. M tuberculosis was predominantly isolated from the lung. Of 358
      positive cultures for M tuberculosis (68 HIV seropositive, 290 presumptively HIV
      seronegative), only 27 isolates (7.6%), almost exclusively derived from presumed
      HIV seronegative patients, were resistant to either isoniazid, rifampicin, or
      both drugs together. No increases in drug-resistant isolates were observed over
      this period. CONCLUSIONS: There has been a considerable increase in the incidence
      of tuberculosis in both HIV seronegative and seropositive populations during the
      study period. The emergence of drug-resistant tuberculosis was not observed.

PMID- 8553270
TI  - Treatment of malignant obstruction of the superior vena cava with the self
      expanding Wallstent.
AB  - BACKGROUND: Obstruction of the superior vena cava (SVC) in malignant disease can
      cause considerable distress to patients. Symptomatic relief can be achieved by
      the percutaneous implantation of a self-expanding stent (Wallstent) into the
      stenosis. METHODS: Fourteen patients with obstruction of the SVC were treated
      with one to three Wallstent endoprostheses. They suffered from advanced
      bronchogenic carcinoma (n = 12), thyroid carcinoma (n = 1), and breast carcinoma
      (n = 1). The indication for stent placement was symptomatic obstruction of the
      SVC and incurable disease. Stenting was performed for symptom relief, and before,
      during, and after courses of radiotherapy or chemotherapy as needed. RESULTS:
      Twelve patients experienced complete symptomatic relief within two days of stent
      placement. Two patients did not benefit. Three patients not given anticoagulation
      developed stent thrombosis between one week and eight months after initial
      placement, and within one day of endobronchial stent implantation with bronchial
      laser therapy or balloon dilatation in all three. Patency of the SVC was achieved
      again by a repeat procedure. CONCLUSIONS: Stent placement for obstruction of the
      SVC gives rapid symptomatic relief. Subsequent endobronchial stent implantation
      with bronchial laser therapy or balloon dilatation could be a risk for caval
      stent occlusion. Stent thrombosis remains a problem in patients who are not
      anticoagulated.

PMID- 8553271
TI  - In vivo assessment of diaphragm contraction by ultrasound in normal subjects.
AB  - BACKGROUND: Ultrasound allows observation of the thickness of the diaphragm in
      the zone of apposition in vivo during relaxation and maximum inspiratory efforts.
      METHODS: Changes of diaphragm thickness were studied by B mode (two dimensional)
      ultrasound in 13 healthy men aged 29-54 years in the seated position. A high
      resolution 7.5 MHz ultrasound transducer was held perpendicular to the chest wall
      in the line of a right intercostal space between the anteroaxillary and mid
      axillary lines to observe the diaphragm in the zone of apposition 0.5-2 cm below
      the costophrenic angle. The changes of thickness were observed while breath
      holding at total lung capacity (TLC), functional residual capacity (FRC), and
      residual volume (RV). At FRC the thickness while relaxing against a closed
      mouthpiece and during a maximum inspiratory mouth pressure (PImax) manoeuvre was
      recorded. The thickening ratio (TR) was calculated as TR = thickness during PImax
      manoeuvre/thickness while relaxing. RESULTS: Mean (SD) thickness was 4.5 (0.9) mm
      at TLC, 1.7 (0.2) mm at FRC, and 1.6 (0.2) mm at RV. During the PImax manoeuvre
      at FRC mean thickness increased from 1.7 (0.2) mm during relaxation to 4.4 (1.4)
      mm, while mean PImax and TR were -104 (33) cm H2O and 2.6 (0.7), respectively.
      There was a high degree of correlation between TR and the pressure achieved
      during the maximum inspiratory manoeuvre (r = -0.82). CONCLUSIONS: Ultrasound
      provides a non-invasive assessment of diaphragm thickness with change of lung
      volume and during the PImax manoeuvre which should prove useful in assessing
      diaphragm mass and contraction in respiratory and muscle disease.

PMID- 8553272
TI  - Unilateral magnetic stimulation of the phrenic nerve.
AB  - BACKGROUND: Electrical stimulation of the phrenic nerve is a useful non
      volitional method of assessing diaphragm contractility. During the assessment of
      hemidiaphragm contractility with electrical stimulation, low twitch
      transdiaphragmatic pressures may result from difficulty in locating and
      stimulating the phrenic nerve. Cervical magnetic stimulation overcomes some of
      these problems, but this technique may not be absolutely specific and does not
      allow the contractility of one hemidiaphragm to be assessed. This study assesses
      both the best means of producing supramaximal unilateral magnetic phrenic
      stimulation and its reproducibility. This technique is then applied to patients.
      METHODS: The ability of four different magnetic coils to produce unilateral
      phrenic stimulation in five normal subjects was assessed from twitch
      transdiaphragmatic pressure (TwPDI) measurements and diaphragmatic electromyogram
      (EMG) recordings. The results from magnetic stimulation were compared with those
      from electrical stimulation. To determine whether the magnetic field affects the
      contralateral phrenic nerve as well as the intended phrenic nerve, EMG recordings
      from each hemidiaphragm were compared during stimulation on the same side and the
      opposite side relative to the recording electrodes. The EMG recordings were made
      from skin surface electrodes in five normal subjects and from needle electrodes
      placed in the diaphragm during cardiac surgery in six patients. Similarly, the
      direction of hemidiaphragm movement was evaluated by ultrasonography. To
      determine the usefulness of the technique in patients the 43 mm mean diameter
      double coil was used in 54 patients referred for assessment of possible
      respiratory muscle weakness. These results were compared with unilateral
      electrical phrenic stimulation, maximum sniff PDI, and TwPDI during cervical
      magnetic stimulation. RESULTS: In the five normal subjects supramaximal
      stimulation was established for eight out of 10 phrenic nerves with the 43 mm
      double coil. Supramaximal unilateral magnetic stimulation produced a higher TwPDI
      than electrical stimulation (mean (SD) 13.4 (2.5) cm H2O with 35 mm coil; 14.1
      (3.8) cm H2O with 43 mm coil; 10.0 (1.7) cm H2O with electrical stimulation).
      Spread of the magnetic field to the opposite phrenic nerve produced a small
      amplitude contralateral diaphragm EMG measured from skin surface electrodes which
      reached a mean of 15% of the maximum EMG amplitude produced by ipsilateral
      stimulation. Similarly, in six patients with EMG activity recorded directly from
      needle electrodes, the contralateral spread of the magnetic field produced EMG
      activity up to a mean of 3% and a maximum of 6% of that seen with ipsilateral
      stimulation. Unilateral magnetic stimulation of the phrenic nerve was rapidly
      achieved and well tolerated. In the 54 patients unilateral magnetic TwPDI was
      more closely related than unilateral electrical TwPDI to transdiaphragmatic
      pressure produced during maximum sniffs and cervical magnetic stimulation.
      Unilateral magnetic stimulation eliminated the problem of producing a falsely low
      TwPDI because of technical difficulties in locating and adequately stimulating
      the nerve. Eight patients with unilateral phrenic nerve paresis, as indicated by
      a unilaterally elevated hemidiaphragm on a chest radiograph and maximum sniff PDI
      consistent with hemidiaphragm weakness, were all accurately identified by
      unilateral magnetic stimulation. CONCLUSIONS: Unilateral magnetic phrenic nerve
      stimulation is easy to apply and is a reproducible technique in the assessment of
      hemidiaphragm contractility. It is well tolerated and allows hemidiaphragm
      contractility to be rapidly and reliably assessed because precise positioning of
      the coils is not necessary. This may be particularly useful in patients. In
      addition, the anterolateral positioning of the coil allows the use of the magnet
      in the supine patient such as in the operating theatre or intensive care unit.

PMID- 8553273
TI  - Effect of spinal surgery on lung function in Duchenne muscular dystrophy.
AB  - BACKGROUND: The effect on subsequent respiratory function of spinal stabilisation
      for scoliosis in Duchenne muscular dystrophy is unclear. In order to clarify this
      clinical problem, changes in the forced vital capacity of a group of children
      with Duchenne muscular dystrophy who had undergone spinal surgery were measured
      and compared with a group of children with Duchenne muscular dystrophy who had
      not had surgery. METHODS: In this retrospective study 17 boys with Duchenne
      muscular dystrophy who underwent spinal stabilisation at a mean age of 14.9 years
      (surgical group) were compared with 21 boys with Duchenne muscular dystrophy who
      had not had surgery (non-surgical group). The mean (SD) Cobb angle of the
      surgical group at 14.9 years was 57 (16.4) degrees, and of the non-surgical group
      at 15 years was 45 (29.9) degrees. Forced vital capacity expressed as percentage
      predicted (% FVC) was measured in total over a seven year period in the surgical
      group and over 6.5 years in the non-surgical group, and regression equations were
      calculated. Survival curves for both groups were also constructed. RESULTS: No
      difference was found between spinal stabilisation (surgical group) and the non
      surgical group in the rate of deterioration of % FVC which was 3-5% per year.
      There was no difference in survival in either group. CONCLUSIONS: Spinal
      stabilisation in Duchenne muscular dystrophy does not alter the decline in
      pulmonary function, nor does it improve survival.

PMID- 8553274
TI  - Continuous nasal positive airway pressure with a mouth leak: effect on nasal
      mucosal blood flux and nasal geometry.
AB  - BACKGROUND: Obstructive sleep apnoea is a common condition. Treatment with nasal
      continuous positive airway pressure (CPAP), while effective and safe, causes
      nasal congestion and stuffiness in some patients. The hypothesis that this study
      aimed to test was that nasal CPAP with a mouth leak and subsequent unidirectional
      airflow across the nasal mucosa causes an increase in nasal mucosal blood flux
      and a fall in both nasal volume and minimal cross sectional area. A secondary aim
      was to study if this could be prevented by humidifying the air inspired with
      nasal CPAP. METHODS: Nasal CPAP was applied to eight normal subjects who kept
      their mouths open until they had expired 500 litres. The effect of this on nasal
      mucosal blood flux and nasal geometry was studied with and without humidification
      using a laser Doppler blood flowmeter and acoustic rhinometer. In addition, nasal
      mucosal blood flux was measured in four of the eight subjects before and after
      nasal CPAP with the mouth closed. RESULTS: Nasal CPAP using room air with the
      mouth closed did not result in any change in nasal mucosal blood flux; with a
      mouth leak nasal CPAP using room air was associated with a 65% increase in nasal
      mucosal blood flux. There was no change in nasal geometry. Nasal CPAP using
      humidified air with a mouth leak did not cause any change in nasal mucosal blood
      flux or nasal geometry. CONCLUSION: Nasal CPAP used with an open mouth leads to
      an increase in nasal mucosal blood flux. This can be prevented by humidifying the
      air inspired with nasal CPAP.

PMID- 8553275
TI  - Evaluation of the effectiveness of four different inhalers in patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: The percentage of patients inhaling their medication effectively
      varies widely, according to methods of assessment and inhalers used. This study
      was carried out to assess differences among four types of inhalers using inhaler
      specific checklists. METHODS: Inhalation technique was evaluated in adult
      patients with chronic obstructive pulmonary disease (COPD). Inhalers investigated
      were either metered dose inhalers (MDIs) or the dry powder inhalers Turbohaler
      (Turbuhaler), Diskhaler, and Rotahaler. Errors were recorded against inhaler
      specific checklists. From these, scores were derived by dividing the number of
      items correctly completed by the total number of items on the checklist and the
      result was expressed as a percentage. For every inhaler "essential actions" were
      identified and scores on these key manoeuvres were calculated. The percentage of
      patients performing all these essential actions correctly was also calculated.
      Scores were also compared with adjustment for differences in relevant patient
      characteristics. RESULTS: Important differences among inhalers were found. Of 152
      patients with COPD (mean (SD) age 55.1 (8.7) years), those with MDIs performed
      worst, especially when only essential items were considered. Patients with a
      Diskhaler did best, although after correction for patient characteristics the
      differences tended to diminish. Only 60% of patients were able to perform all
      essential inhaler actions satisfactorily. Of those using the Diskhaler, 96% did
      so correctly, while the corresponding figure for those using the MDI was only
      24%. CONCLUSIONS: Many patients with COPD use their inhaler ineffectively. After
      adjusting for patient characteristics, differences among inhalers, although less
      pronounced, persist. Patients using a Diskhaler made fewest errors, while most
      patients using MDIs made crucial mistakes.

PMID- 8553276
TI  - Health effects of an air pollution episode in London, December 1991.
AB  - BACKGROUND: In December 1991 London experienced a unique air pollution episode
      during which concentrations of nitrogen dioxide rose to record levels, associated
      with moderate increases in black smoke. The aim of this study was to investigate
      whether this episode was associated with adverse health effects and whether any
      such effects could be attributed to air pollution. METHODS: The numbers of deaths
      and hospital admissions occurring in Greater London during the week of the
      episode were compared with those predicted using data from the week before the
      episode and from equivalent periods from the previous four years. Relative risks
      (RR) (episode week versus predicted) for adverse health events were estimated
      using log linear modelling and these were compared with estimates from control
      areas which had similar cold weather but without increased air pollution.
      RESULTS: In all age groups mortality was increased for all causes (excluding
      accidents) (relative risk = 1.10) and cardiovascular diseases (1.14); non
      significant increases were observed for all respiratory diseases (1.22),
      obstructive lung diseases (1.23), and respiratory infections (1.23). In the
      elderly (65 + years) the relative risk of hospital admission was increased for
      all respiratory diseases (1.19) and for obstructive lung diseases (1.43), and a
      non-significant increase was observed for ischaemic heart disease (1.04). In
      children (0-14 years) there was no increase in admissions for all respiratory
      diseases and only a small non-significant increase for asthma. When compared with
      control areas the relative risks became non-significant but remained increased.
      CONCLUSIONS: The air pollution episode was associated with an increase in
      mortality and morbidity which was unlikely to be explained by the prevailing
      weather, a coincidental respiratory epidemic, or psychological factors due to
      publicity. Air pollution is a plausible explanation but the relative roles of
      nitrogen dioxide and particulates cannot be distinguished.

PMID- 8553278
TI  - Accuracy of an intelligent CPAP machine with in-built diagnostic abilities in
      detecting apnoeas: a comparison with polysomnography.
AB  - BACKGROUND: In patients with sleep apnoea early diagnostic evaluation and
      treatment may be delayed due to limited access to full polysomnography (PSG). For
      "typical" patients, simplified strategies are needed. A study was performed to
      evaluate the accuracy of a new continuous positive airway pressure (CPAP) device
      with in-built diagnostic abilities (Autoset) in detecting apnoeas. METHODS:
      Twenty seven patients underwent full overnight polysomnography. Data with the
      Autoset were acquired simultaneously. Standard nasal prongs were used. Apnoeas
      were detected by special analysis of the flow signal. As the Autoset derives all
      its data from one signal, careful examination of the raw data is important to
      assess the quality of the flow signal. RESULTS: There was a correlation between
      the apnoea index (AI) assessed by the Autoset (AI-Autoset) and by polysomnography
      AI-PSG (r = 0.85) and between the AI-Autoset and the apnoea/hypopnoea index (AHI)
      during polysomnography (r = 0.87). The Autoset identified patients with an AHI
      PSG of > 20 (a level of respiratory disturbance that would warrant consideration
      for treatment in most centres for sleep disorders) with a sensitivity of 82% and
      a specificity of 90%. CONCLUSIONS: The good correlation between the apnoea index
      measured by the Autoset and by polysomnography, and the high sensitivity in
      detecting patients with an AHI of > 20, may make the Autoset a valuable tool for
      the management of typical patients with sleep apnoea. However, very low values
      for nasal ventilation on the printout raises the suspicion of poor signal quality
      and misleading results.

PMID- 8553277
TI  - Outcome of Burkholderia (Pseudomonas) cepacia colonisation in children with
      cystic fibrosis following a hospital outbreak.
AB  - BACKGROUND: While there are reports on the outcome in adults and teenagers with
      cystic fibrosis of colonisation with Burkholderia (Pseudomonas) cepacia, there is
      little information in children. METHODS: In December 1991 only one of 115
      children with cystic fibrosis attending a paediatric centre was colonised with B
      cepacia. Over the next 12 months there was a rapid increase with 23 (20%)
      becoming colonised; eighteen (79%) of these became colonised in hospital at a
      time that overlapped with the admission of a B cepacia positive child. Three
      different bacteriocin types were isolated, with one type (S22/PO) being present
      in 17 (74%) patients. The outcome for children who became colonised with B
      cepacia was compared with that in 33 children who continued to be colonised with
      Pseudomonas aeruginosa alone. RESULTS: Children colonised with B cepacia were
      older and more poorly nourished than those colonised with P aeruginosa, but did
      not have poorer pulmonary function. After colonisation, the forced expiratory
      volume in one second (FEV1) deteriorated between consecutive annual tests, with
      the average deterioration being greater in those with higher initial levels. Five
      children with B cepacia died from respiratory failure although none showed a
      fulminant deterioration. Introduction of segregation measures within hospital led
      to a dramatic decrease in the number of newly colonised patients. CONCLUSIONS:
      This study provides further evidence for person-to-person spread of B cepacia and
      confirms the effectiveness of simple isolation measures in interrupting spread.
      Colonisation with B cepacia and P aeruginosa in children is associated with a
      more rapid decline in lung function and a significantly increased mortality
      compared with cases colonised with P aeruginosa alone.

PMID- 8553279
TI  - Comparison of polysomnography with ResCare Autoset in the diagnosis of the sleep
      apnoea/hypopnoea syndrome.
AB  - BACKGROUND: Increasing referral numbers make the development of simplified
      accurate methods of diagnosing the sleep apnoea/hypopnoea syndrome highly
      desirable. The accuracy of one such system--the ResCare Autoset--has been
      examined. METHODS: Thirty one consecutive patients assessed by polysomnography
      had simultaneous monitoring of their respiratory pattern using the Autoset
      system. The Autoset detects episodes of flattening of the flow/time profile using
      nasal cannulae. RESULTS: There was a good correlation (r = 0.85) between the
      number of apnoeas+hypopnoeas/hour in bed recorded using polysomnography and the
      Autoset system. The median difference in such events was 3.1 (95% confidence
      interval 8.4 to -1.6)/hour in bed. In two patients the Autoset scored 70
      apnoeas+hypopnoeas/hour in bed compared with 34 apnoeas+hypopnoeas with 35
      arousals/hour in bed by polysomnography; however, this did not alter the
      diagnostic category of either patient. Autoset gave a sensitivity of 100%,
      specificity of 92%, positive predictive value of 92%, and negative predictive
      value of 100%, which was better than oximetry alone. A sleep study using the
      Autoset system costs 14 pounds compared with 126 pounds for polysomnography.
      CONCLUSIONS: The Autoset is clinically useful for diagnosing the sleep
      apnoea/hypopnoea syndrome.

PMID- 8553280
TI  - Sleep-related breathing disorders. 6. Obstructive sleep apnoea syndrome in
      infants and children: established facts and unsettled issues.
AB  - The presence of increased upper airway resistive loads during sleep can now be
      diagnosed by paediatricians. However, diagnostic criteria need to be further
      clarified to allow accurate identification of episodes of partial airway
      obstruction. New technological advances can be expected to help to determine the
      clinical usefulness of ambulatory testing during sleep and thus to establish the
      indications for polysomnographic investigations in the laboratory. A thorough
      investigation of the anatomical abnormalities that contribute to airways
      obstruction is essential for selecting the most appropriate therapy. However, the
      order in which these investigations should be performed remains unclear. The
      diagnostic tools, including questionnaires and sleep testing, and methods aimed
      at investigating pathophysiological mechanisms should be standardised for
      multicentre studies. Familial factors should be taken into account. The best
      strategy for preventing the complications of the OSA syndrome is to identify the
      disorder as early as possible. This requires close cooperation between adult
      physicians and paediatricians called upon to evaluate sleep-related disorders.

PMID- 8553282
TI  - Treatment of adenoviral pneumonitis with intravenous ribavirin and
      immunoglobulin.
AB  - A 67 year old woman developed a severe adenoviral pneumonitis whilst receiving
      immunosuppressive therapy. She showed clinical and radiological evidence of a
      response to treatment with nebulised and intravenous ribavirin and intravenous
      pooled normal human immunoglobulin. To our knowledge this is the first time that
      such a therapeutic approach has been used in the treatment of a condition which
      normally carries a very high mortality.

PMID- 8553281
TI  - Restriction fragment length polymorphism typing of Mycobacterium tuberculosis.

PMID- 8553284
TI  - Commentary: severe varicella/zoster and adenovirus infections in
      immunocompromised patients.

PMID- 8553283
TI  - Fatal varicella zoster infection in a severe steroid dependent asthmatic patient
      receiving methotrexate.
AB  - A case is described of fatal haemorrhagic varicella zoster in a steroid dependent
      asthmatic patient concurrently receiving methotrexate. The future management of
      patients on immunosuppressive steroid sparing drugs is discussed.

PMID- 8553285
TI  - Tuberculosis of the sternum presenting as metastatic disease.
AB  - The case is presented of a 59 year old Saudi Arabian woman with sternal and
      vertebral tuberculous osteomyelitis and a benign breast mass simulating
      metastatic disease. This case illustrates the diagnostic difficulties that may be
      encountered in the diagnosis of tuberculous osteomyelitis.

PMID- 8553286
TI  - Pulmonary benign metastasising leiomyoma: response to treatment with goserelin.
AB  - Benign metastasising leiomyoma is a rare disease occurring predominantly in women
      of childbearing age and is hormonally influenced. The response of the disease to
      the luteinising hormone releasing hormone analogue goserelin is reported.

PMID- 8553287
TI  - HIV related bronchiectasis.

PMID- 8553288
TI  - Beta 2 agonist/antagonist activity of salbutamol.

PMID- 8553289
TI  - AIDS and the lung: update 1995. 1. Pneumocystis carinii pneumonia.

PMID- 8553290
TI  - Paradoxical vocal cord adduction in cystic fibrosis.

PMID- 8553291
TI  - Upper respiratory tract infections and exercise.
AB  - The epidemiological data suggest that endurance athletes are at increased risk
      for upper respiratory tract infections during periods of heavy training and the 1
      2 week period following a marathon or similar event. At present there is no clear
      indication that chronic alterations in immune function explain this increased
      risk. Following acute bouts of prolonged heavy endurance exercise, several
      components of the immune system are suppressed for several hours. This has led to
      the concept of the "open window" theory described as the 1-9 hour period
      following prolonged endurance exercise when host defense is decreased and the
      risk of upper respiratory tract infection is increased.

PMID- 8553292
TI  - Epstein-Barr virus and cryptogenic fibrosing alveolitis.

PMID- 8553293
TI  - Epstein-Barr virus replication within pulmonary epithelial cells in cryptogenic
      fibrosing alveolitis.
AB  - BACKGROUND: Cryptogenic fibrosing alveolitis (synonymous with idiopathic
      pulmonary fibrosis) is a clinically heterogeneous condition in which the
      precipitating factor is unclear. Both environmental and infective factors have
      been implicated. An association between Epstein-Barr virus (EBV) and cryptogenic
      fibrosing alveolitis was suggested over a decade ago by a study based on EBV
      serology, but the significance of this has been unclear. METHODS: Lung tissue
      obtained surgically from patients (n = 20) with cryptogenic fibrosing alveolitis
      was investigated for evidence of EBV replication and compared with lung tissue
      from 21 control patients. Fourteen of the 20 patients had received no specific
      therapy for cryptogenic fibrosing alveolitis at the time of biopsy. Monoclonal
      antibodies directed against the EBV viral antigens, EBV viral capsid antigen
      (VCA) and gp 340/220 antigen, which are expressed during the lytic phase of the
      EBV life cycle, were studied. RESULTS: Fourteen (70%) of the 20 patients with
      cryptogenic fibrosing alveolitis were positive for both EBV VCA and gp 340/220
      compared with two (9%) of the 21 controls. In the patients with cryptogenic
      fibrosing alveolitis viral replication was localised to pulmonary epithelial
      cells using epithelial cell markers, and immunohistochemical analysis confirmed
      the staining to be within type II alveolar cells. CONCLUSIONS: This is the first
      report of in vivo EBV replication within epithelial cells of the lower
      respiratory tract in an immunocompetent human host. Furthermore, this suggests
      that EBV may be an immune trigger or contribute to lung injury in cryptogenic
      fibrosing alveolitis, thus offering a potential new avenue of treatment.

PMID- 8553294
TI  - Pulmonary complications of HIV disease: 10 year retrospective evaluation of
      yields from bronchoalveolar lavage, 1983-93.
AB  - BACKGROUND: Pulmonary disease is a major contributor to morbidity and mortality
      in patients with HIV infection and AIDS. The aim of this study was to describe
      bronchoscopic findings and the spectrum of pulmonary pathogens in HIV
      seropositive patients undergoing investigation of respiratory disease over a 10
      year period in a major UK referral centre. METHODS: Recruitment was procedure
      based with data being captured when bronchoscopy was clinically indicated. Data
      were evaluated from 580 HIV seropositive patients (559 men, age 13-65 years) over
      a 10 year period from June 1983 to March 1993. RESULTS: A total of 947
      bronchoscopies was performed. The most frequent pulmonary pathogen isolated from
      bronchoalveolar lavage (BAL) fluid in 44% of all bronchoscopies was Pneumocystis
      carinii. Of all patients studied, 324 (55%) had at least one cytologically
      confirmed episode of P carinii pneumonia; this was AIDS defining in 219 (38%) of
      patients who underwent bronchoscopy. Between 1987 and 1993 the overall diagnostic
      yield from BAL fluid was 76%; 25% of all bronchoscopies yielded positive
      microbiological results, the most frequent isolates being Staphylococcus aureus,
      Streptococcus pneumoniae, Pseudomonas spp, and Haemophilus influenzae.
      Mycobacteria were identified in 8% of patients; M tuberculosis was the most
      common being identified in 3% of lavage samples and in 4% of patients. No drug
      resistant M tuberculosis was found. Viral isolates (mainly cytomegalovirus) were
      identified in up to 31% of BAL fluid samples. Endobronchial Kaposi's sarcoma was
      seen in 15% of patients at bronchoscopy. CONCLUSIONS: Of the 1956 newly diagnosed
      HIV seropositive patients receiving clinical care at St Mary's Hospital over this
      period, approximately 30% underwent bronchoscopy. Diagnostic rates for P carinii
      pneumonia, endobronchial Kaposi's sarcoma, and bacterial and mycobacterial
      infection have remained largely constant since 1989. Bronchoalveolar lavage
      produces high diagnostic yields generally, and P carinii pneumonia remains a
      common cause of pulmonary disease in these patients.

PMID- 8553295
TI  - Long term effect of erythromycin therapy in patients with chronic Pseudomonas
      aeruginosa infection.
AB  - BACKGROUND: Diffuse panbronchiolitis is a chronic infection of the lower
      respiratory tract common among the Japanese people, with a persistent Pseudomonas
      aeruginosa infection in the late stage and sustained neutrophil retention in the
      airways. The long term effect of erythromycin was examined retrospectively in a
      group of patients with diffuse panbronchiolitis, with and without P aeruginosa
      infection, and the relationship between drug-induced bacterial clearance and
      clinical improvement was investigated. METHODS: The history, daily volume of
      sputum, type of organisms in sputum cultures, pulmonary function tests, arterial
      blood gas tensions, and chest radiographs were compared in 16 patients with
      diffuse panbronchiolitis with P aeruginosa infection and 12 without. The total
      and differential cell counts in the bronchoalveolar lavage (BAL) fluid were
      compared in 14 of the 28 patients (five of whom were infected with P aeruginosa)
      before and after 1-12 months of treatment with erythromycin (600 mg/day). The
      outcome of treatment in patients showing clearance of organisms on repeated
      sputum cultures was compared with that in those demonstrating persistence of
      bacteria in the sputum and patients with normal flora. RESULTS: Erythromycin
      improved respiratory function and arterial blood gas tensions irrespective of the
      presence or absence of P aeruginosa in the sputum. Treatment also resulted in a
      reduction in the BAL fluid total cell count and the percentage of neutrophils in
      both groups of patients. There were no differences between patients in whom the
      bacteria cleared and those with persistent bacteria or patients with a normal
      flora with regard to the degree of improvement of respiratory function, arterial
      blood gas tensions, and BAL fluid cell composition. CONCLUSION: The results
      suggest that the efficacy of erythromycin in diffuse pan-bronchiolitis may be due
      to anti-inflammatory effect, independent of P aeruginosa infection or bacterial
      clearance.

PMID- 8553296
TI  - Diagnostic value of blood cytokine concentrations in acute pneumonia.
AB  - BACKGROUND: The role of cytokines in the pathogenesis of pneumonia is still
      poorly understood. In a previous study the diagnostic value of measuring blood
      concentrations of interleukin 6 and interferon gamma was established. In the
      present study the value of blood concentrations of interleukin 8, granulocyte
      colony stimulating factor, and lactoferrin as markers of bacteraemic pneumonia is
      evaluated. METHODS: The circulating concentrations of interleukin 8 (IL-8),
      granulocyte-colony stimulating factor (G-CSF), and lactoferrin were measured in
      14 patients with bacteraemic pneumococcal pneumonia and 49 patients with atypical
      pneumonia or influenza A infection using enzyme immunoassays. RESULTS: Serum G
      CSF concentrations were higher in the group with bacteraemic pneumococcal
      pneumonia, and G-CSF values correlated with the white blood cell count and levels
      of C-reactive protein (CRP). The levels of IL-8 were higher in the group with
      bacteraemic pneumococcal pneumonia than the groups with Chlamydia pneumonia,
      Legionella pneumonia, or influenza A infection, but there was no difference when
      compared with the group with Mycoplasma pneumonia. A white blood cell count of >
      15 x 10(9)/l was highly suggestive of bacteraemic pneumonia. The concentrations
      of lactoferrin were raised in all groups except those with influenza A infection,
      but no difference was found between the different aetiological groups. A
      correlation was found between lactoferrin and white blood cell counts.
      CONCLUSIONS: Serum G-CSF and IL-8 concentrations are potential markers of
      bacteraemic pneumonia.

PMID- 8553297
TI  - Transthoracic needle biopsy of thoracic tumours by a colour Doppler ultrasound
      puncture guiding device.
AB  - BACKGROUND: Ultrasound guided transthoracic needle aspiration biopsy has recently
      been used to obtain specimens for histological diagnosis of pulmonary and
      mediastinal tumours. Conventional real time, grey scale puncture guiding devices
      cannot differentiate vascular structures, and clear visualisation of the needle
      shaft or tip within a desired target is not always possible. This study describes
      a new built-in colour Doppler ultrasound puncture guiding device and assesses the
      relative safety of transthoracic needle aspiration biopsy of thoracic tumours by
      grey scale or colour Doppler ultrasound guidance. METHODS: Thirty patients with
      radiographic evidence of pulmonary (22 patients) or mediastinal tumours (eight
      patients) underwent ultrasonographic evaluation and transthoracic needle
      aspiration biopsy by using the colour Doppler ultrasound puncture guiding device
      (Aloka UST 5045P-3.5). These tumours were initially examined by grey scale
      ultrasound, and colour Doppler imaging was then used to evaluate the number of
      blood vessels surrounding and within the target tumour and the possibility of
      visualisation of the needle shaft or needle tip during the aspiration biopsy
      procedure. RESULTS: The colour Doppler ultrasound guiding device was far superior
      to the grey scale device for identification of the number of vessels surrounding
      or within the target tumour (83% v 20%) and for visualisation of the needle shaft
      or needle tip (80% v 17%). CONCLUSIONS: By using the colour Doppler ultrasound
      puncture device, vascular structures surrounding or within the target tumour can
      be verified. Visualisation of the needle shaft or tip is also better. Biopsy
      routes can be selected to avoid puncturing vessels. This approach should be
      particularly helpful for guiding biopsies of mediastinal tumours, where
      puncturing the heart or great vessels is a potential complication.

PMID- 8553298
TI  - Excessive thoracic computed tomographic scanning in sarcoidosis.
AB  - BACKGROUND: The clinical value of computed tomographic (CT) scanning of the chest
      in the initial assessment of sarcoidosis was investigated. METHODS: One hundred
      consecutive patients referred to the sarcoidosis outpatient services of the Mount
      Sinai Medical Center, New York from 1990 to 1992 with a presumptive diagnosis of
      sarcoidosis were studied. The diagnosis was subsequently confirmed in all by a
      positive tissue biopsy sample or the Kveim-Siltzbach test. Clinical and
      laboratory data of each patient were reviewed. Chest radiographs were classified
      according to the classical stages of sarcoidosis. Thirty five of the 100 patients
      had a CT scan of the chest performed before presentation. The CT scans were
      compared with the presenting clinical data and standard chest radiographs in
      order to determine if they yielded useful additional information regarding
      diagnosis or treatment. RESULTS: The chest CT scan revealed no additional
      clinically relevant information compared with conventional chest radiographs in
      any of the 35 studies performed. In two patients mediastinal adenopathy was
      detected by CT scan which was not seen on standard radiographs. Two patients
      thought to exhibit hilar adenopathy and pulmonary infiltrations by standard
      radiography had no parenchymal disease on the CT scan. Bilateral parenchymal
      infiltrates were seen in one patient which were interpreted as unilateral
      infiltrates by standard radiographs. The variance between conventional
      radiographs and CT scans in these five patients was not clinically valuable.
      CONCLUSIONS: CT scans of the chest do not add clinically useful information to
      the standard chest radiographs in the initial assessment of sarcoidosis in
      patients presenting with the typical standard radiological patterns. CT scanning
      of the thorax is indicated in patients with proven or suspected sarcoidosis when
      the standard chest radiographs are normal or not typical of sarcoidosis, when
      signs or symptoms of upper airway obstruction are present, when the patient has
      haemoptysis, if there is a suspicion of a complicating second intrathoracic
      disease, or the patient is a candidate for lung transplantation.

PMID- 8553299
TI  - Bronchogenic carcinoma: incidence of metastases to normal sized lymph nodes.
AB  - BACKGROUND: The incidence of metastases to mediastinal lymph nodes was evaluated
      in patients with normal sized mediastinal nodes on the computed tomographic (CT)
      scan who underwent thoracotomy. The use of hilar lymph nodes in predicting
      mediastinal lymph node metastases was also assessed. METHODS: Ninety patients
      with non-small cell lung cancer who later underwent thoracotomy wer prospectively
      examined by CT scanning. Lymph nodes with a short axis diameter of 10 mm or more
      were considered abnormal. RESULTS: Mediastinal lymph node metastases were present
      at thoracotomy in 19 patients (21%). In 14 these lymph node metastases were
      misdiagnosed because the nodes were normal in size on the CT scan. In only one of
      the 19 patients with N2 nodes was an N1 lymph node enlarged, and four of the 19
      patients with N2 nodes had metastases to these mediastinal nodes without N1
      disease ("skipping metastases"). CONCLUSIONS: Metastases in normal sized nodes
      seen on the CT scan are a major problem in staging. Hilar lymph nodes did not
      help to predict reliably the presence or absence of metastases to the mediastinal
      lymph nodes.

PMID- 8553300
TI  - Long term clinical comparison of single versus twice daily administration of
      inhaled budesonide in moderate asthma.
AB  - BACKGROUND: Inhaled steroids are widely used in the treatment of mild to moderate
      asthma. However, long term compliance with inhaled steroids is poor and
      administration of a single daily dose may improve compliance. METHODS: A double
      blind, randomised study was performed to determine whether inhaled steroids given
      once daily at bedtime are as efficacious as a twice daily regimen in the long
      term maintenance of moderate asthmatic patients. Forty adults of mean age 37
      years with moderate asthma (mean (SE) forced expiratory volume in one second
      (FEV1) 73.6 (1.4)% predicted, mean morning peak expiratory flow (PEF) 328 l/min)
      were randomised to receive either a twice daily dose (400 micrograms morning and
      bedtime) of inhaled budesonide (group A) or a once daily dose of 800 micrograms
      (group B) and were followed for a period of 12 months. Asthma symptom scores
      (assessed according to a modified Borg scale), inhaled beta 2 agonist
      consumption, and peak expiratory flow rates were recorded daily. Spirometry and
      airways responsiveness to methacholine (PC20) were measured at the end of each
      period of three months of treatment. RESULTS: There was no difference between the
      two groups at baseline and during the follow up period in the PC20 for
      methacholine. However, a difference was seen between the two groups in the mean
      daily number of beta 2 agonist inhalations (1.4 (0.1) puffs/patient/day in group
      A v 2.3 (0.1) in group B), the PEF variability (episodes of decrease in PEF of >
      20%) (0.22 (0.01) episodes/patient/day in group A v 0.40 (0.02) in group B), and
      for asthma symptom scores (0.30 (0.04) in group A v 0.42 (0.06) in group B) for
      the 12 month period of the study. CONCLUSIONS: Although both regimens provide
      good clinical control, twice daily doses of 400 micrograms inhaled budesonide are
      more effective than a single dose of 800 micrograms at bedtime in the long term
      control of stable moderate asthma.

PMID- 8553301
TI  - Compliance with inhaled asthma medication in preschool children.
AB  - BACKGROUND: Previous studies have shown poor compliance with regular drug therapy
      in children and adults with asthma. In preschool children the parents supervise
      and are responsible for drug administration, but little is known of compliance in
      this group. In addition, there are few data on the patterns of drug use of
      inhaled prophylactic asthma therapy or of the relation between compliance and
      symptom control. A study was undertaken to address these issues with the
      hypothesis that parental supervision would result in good compliance. METHODS:
      The subjects were 29 asthmatic children aged 15 months to five years already
      established on inhaled prophylactic medication delivered through a large volume
      spacer. The prescribed drug regimens varied between subjects. This was an
      observational study using an electronic inhaler timer device to record the date
      and time of each actuation of the aerosol canister. Diary cards were used for
      parallel recording of symptoms and parentally reported compliance with a drug
      regimen. RESULTS: Variable and generally poor compliance was demonstrated with a
      median of 50% of study days with full compliance (subject range 0-94%) and an
      overall median of 77% of prescribed doses of therapy taken during the study
      period. No relation was found between frequency of prescribed regimen and good
      compliance. Day care was associated with poorer compliance. No relation between
      good compliance and low symptom scores was found. CONCLUSION: Compliance with
      inhaled prophylactic therapy is poor in preschool children with asthma whose
      medication is administered under parental supervision.

PMID- 8553302
TI  - Measuring the systemic effects of inhaled beclomethasone: timed morning urine
      collections compared with 24 hour specimens.
AB  - BACKGROUND: Inhaled glucocorticoid therapy has systemic effects including
      hypothalamic-pituitary-adrenal (HPA) suppression. The optimal test for detecting
      these effects has not been defined. METHODS: Timed urine collections and 09.00
      hour plasma cortisol levels were obtained from 12 normal volunteers receiving
      inhaled placebo, beclomethasone (BDP) 800 or 2000 micrograms/day. The 24 hour
      urine samples were collected as follows: first hour after waking (hour 1), the
      next two hours after waking (hours 2 and 3), remainder of day, and overnight,
      with results expressed as urine cortisol/creatinine (UCC) ratios and as hourly
      cortisol output in the timed collections. Twenty four hour urinary cortisol
      excretion was also calculated. Medication was blinded and given in random order
      with a washout period of at least 11 days between each treatment arm. RESULTS:
      None of the UCC ratios changed with BDP 800 micrograms/day. UCC ratios at hour 1,
      hour 2 and 3, and overnight, and 24 hour urinary free cortisol excretion were
      reduced after BDP 2000 micrograms/day, whilst remainder of day UCC ratio and the
      plasma cortisol level did not change significantly. Cortisol output showed
      similar changes. In a follow up study BDP 1400 micrograms/day also reduced UCC
      ratios for the first two hours after waking. CONCLUSIONS: UCC ratios are as
      sensitive as the more cumbersome 24 hour urinary free cortisol excretion, and
      more sensitive than single morning plasma cortisol measurements, in detecting the
      effects of inhaled beclomethasone on the HPA axis.

PMID- 8553303
TI  - Significant differences in flow standardised breath sound spectra in patients
      with chronic obstructive pulmonary disease, stable asthma, and healthy lungs.
AB  - BACKGROUND: Spectral characteristics of breath sounds in asthma and chronic
      obstructive pulmonary disease (COPD) have not previously been compared, although
      the structural differences in these disorders might be reflected in breath
      sounds. METHODS: Flow standardised inspiratory breath sounds in patients with
      COPD (n = 17) and stable asthma (n = 10) with significant airways obstruction and
      in control patients without any respiratory disorders (n = 11) were compared in
      terms of estimates of the power spectrum. Breath sounds were recorded
      simultaneously at the chest and at the trachea. RESULTS: The median frequency
      (F50) of the mean (SD) breath sound spectra recorded at the chest was higher in
      asthmatics (239 (19) Hz) than in both the control patients (206 (14) Hz) and the
      patients with COPD (201 (21) Hz). The total spectral power of breath sounds
      recorded at the chest in terms of root mean square (RMS) was higher in asthmatics
      than in patients with COPD. In patients with COPD the spectral parameters were
      not statistically different from those of control patients. The F50 recorded at
      the trachea in the asthmatics was significantly related to forced expiratory
      volume in one second (FEV1) (r = -0.77), but this was not seen in the other
      groups. CONCLUSIONS: The observed differences in frequency content of breath
      sounds in patients with asthma and COPD may reflect altered sound generation or
      transmission due to structural changes of the bronchi and the surrounding lung
      tissue in these diseases. Spectral analysis of breath sounds may provide a new
      non-invasive method for differential diagnosis of obstructive pulmonary diseases.

PMID- 8553304
TI  - Spectral characteristics of chest wall breath sounds in normal subjects.
AB  - BACKGROUND: This study was carried out to establish a reliable bank of
      information on the spectral characteristics of chest wall breath sounds from
      healthy men and women, both non-smokers and smokers. METHODS: Chest wall breath
      sounds from 272 men and 81 women were measured using contact acoustic sensors,
      amplifiers, and fast Fourier transform (FFT) based spectral analysis software.
      Inspiratory and expiratory sounds were picked up at three standard locations on
      the chest wall during breathing at flows of 1-2 l/s and analysed breath by breath
      in real time. RESULTS: The amplitude spectrum of normal chest wall breath sounds
      has two linear parts in the log-log plane--low and high frequency segments--that
      are best characterised by their corresponding regression lines. Four parameters
      are needed and are sufficient for complete quantitative representation of each of
      the spectra: the slopes of the two regression lines plus the amplitude and
      frequency coordinates of their intersection. The range of slopes of the high
      frequency lines was -12.7 to -15.2 dB/oct during inspiration and -13.4 to -20.3
      dB/oct during expiration. The frequency at which this line crossed the zero dB
      level--that is, the amplitude resolution threshold of the system--was designated
      as the maximal frequency (Fmax) which varied from 736 to 999 Hz during
      inspiration and from 426 to 796 Hz during expiration with higher values in women
      than in men. The mean (SD) regression coefficient of the high frequency line was
      0.89 (0.05). CONCLUSIONS: These data define the boundaries of normal chest wall
      breath sounds and may be used as reference for comparison with abnormal sounds.

PMID- 8553305
TI  - Genetic and clinical features of patients with cystic fibrosis diagnosed after
      the age of 16 years.
AB  - BACKGROUND: Cystic fibrosis is usually diagnosed in childhood, but a number of
      patients are not diagnosed until adulthood. The aim of this study was to
      investigate whether patients diagnosed at an older age had a different genetic
      constitution, manifestations of disease, and prognosis from those diagnosed at an
      early age. METHODS: Clinical data and results of lung function tests and DNA
      analysis of 143 adult patients with cystic fibrosis were entered into a
      computerised database. Patients diagnosed before their 16th birthday (early
      diagnosis, ED) were compared with those diagnosed at 16 years of age or older
      (late diagnosis, LD). RESULTS: Mean age of diagnosis of the ED group was 4.6
      years compared with 27.7 years for the LD group. Mean (SD) percentage predicted
      pulmonary function was better for the LD group than for the ED group: forced
      expiratory volume in one second (FEV1) 72.5 (31.1)% and 52.0 (24.8)%, and forced
      vital capacity (FVC) 89.8 (25.7)% and 71.9 (23.0)%, respectively. Colonisation
      with Pseudomonas aeruginosa was present in 70% of the ED group and 24% of the LD
      group. In the ED group 81% had pancreatic insufficiency compared with only 12% of
      the LD group. None of the LD group was homozygous for delta F508 compared with
      58% of the ED group. In the LD group 72% were compound AF508 heterozygotes and
      28% had two non-delta F508 mutations. CONCLUSIONS: Among this group of 143 adult
      patients with cystic fibrosis late diagnosis is caused mainly by delayed
      expression and mild progression of clinical symptoms. Late diagnosis is
      associated with milder pulmonary disease, less pancreatic insufficiency, and
      different cystic fibrosis mutations. Since mortality in cystic fibrosis depends
      on the progression of pulmonary disease, patients with a late diagnosis have a
      better prognosis than those diagnosed early.

PMID- 8553306
TI  - Randomised trial of corticosteroids in the treatment of tuberculous pleurisy.
AB  - BACKGROUND: Tuberculous pleurisy can result in pleural fibrosis, calcification
      and thickening. To prevent these complications, corticosteroids are frequently
      used in addition to antituberculous drugs; however, new therapeutic regimens can
      control the disease and minimise the sequelae, and there is no convincing
      evidence of the benefit of the use of corticosteroids as adjuvant therapy.
      METHODS: Patients received isoniazid 5 mg/kg and rifampicin 10 mg/kg daily for
      six months. Additionally, they were randomly assigned to a double blind treatment
      with either prednisone (1 mg/kg/day for 15 days and then tapering off) or placebo
      during the first month of treatment. Different clinical, radiological, and
      functional parameters were evaluated to assess the effect of corticosteroids.
      RESULTS: Fifty seven patients received prednisone and 60 placebo. At the end of
      the treatment the clinical outcome, the rate of reabsorption of the pleural
      fluid, the pleural sequelae, as well as lung capacity were similar in both
      groups. CONCLUSIONS: Corticosteroids do not influence the clinical outcome or the
      development of long term pleural sequelae in tuberculous pleurisy.

PMID- 8553307
TI  - Hypoxaemia and release of endothelin-1.
AB  - BACKGROUND: Secretion of the vasoconstrictor peptide endothelin-1 from vascular
      endothelium is increased by various stimuli. Whether hypoxaemia affects plasma
      levels of endothelin-1 in humans is unknown, but this may be important in the
      haemodynamic response to hypoxaemia. The plasma endothelin-1 concentrations in
      hypoxaemic humans has therefore been measured. METHODS: Plasma levels of
      endothelin-1 were measured by specific radioimmunoassay in 10 control subjects at
      rest and following 30 minutes of acute hypoxaemia (SaO2 75-80%) induced by
      breathing a nitrogen/oxygen mixture, and in 10 patients with hypoxaemic cor
      pulmonale. RESULTS: The plasma endothelin-1 concentration in control subjects was
      increased from a mean (SE) of 0.90 (0.11) pmol/l at baseline to 2.34 (0.34)
      pmol/l during hypoxaemia. In patients with cor pulmonale the plasma endothelin-1
      concentration was 2.96 (0.34) pmol/l, raised in comparison with control subjects
      at rest but similar to levels in controls during hypoxaemia. CONCLUSIONS: Plasma
      levels of endothelin-1 were increased by hypoxaemia in humans. The raised levels
      observed in patients with cor pulmonale may largely be attributable to the
      effects of hypoxaemia, although the pathophysiological significance of these
      observations remains to be established.

PMID- 8553309
TI  - Successful extracorporeal membrane oxygenation (ECMO) support for fulminant
      community-acquired pneumococcal pneumonia.
AB  - A case is described of fulminant community-acquired pneumococcal pneumonia in a
      16 year old girl with no previous history of respiratory disease or any
      predisposing factors. She required extracorporeal membrane oxygenation (ECMO)
      until the diagnosis could be made and appropriate antibiotic therapy established.

PMID- 8553308
TI  - Sleep-related breathing disorders. 7. Sleep and breathing problems in general
      medicine.

PMID- 8553310
TI  - Recombinant human DNase in management of lobar atelectasis due to retained
      secretions.
AB  - Recombinant human deoxyribonuclease (rhDNase) is an agent which reduces the
      viscoelasticity of purulent sputum. Two cases are reported in which rhDNase was
      utilised for the management of lobar atelectasis due to retained purulent
      secretions.

PMID- 8553311
TI  - Use of nebulised liposomal amphotericin B in the treatment of Aspergillus
      fumigatus empyema.
AB  - A 28 year old man with asthma, bronchopulmonary aspergillosis, pulmonary
      thromboembolic disease, and pulmonary hypertension developed Aspergillus
      fumigatus empyema complicating a pneumothorax. His condition progressively
      deteriorated despite treatment with intravenous and intrapleural amphotericin B,
      but improved promptly after substituting nebulised liposomal amphotericin B and
      oral itraconazole. This experience suggests that nebulised liposomal amphotericin
      B is well tolerated and merits further assessment in the treatment of pulmonary
      fungal disease.

PMID- 8553312
TI  - Sarcoidosis presenting with chylothorax.
AB  - A patient in whom chylothorax was the presenting feature of sarcoidosis is
      reported. Mediastinal lymphadenopathy was shown by computed tomographic scanning.
      Obstruction of the thoracic duct by enlarged lymph nodes or fibrosis is the
      probable cause of chylothorax in this case. The association of chylothorax and
      sarcoidosis is extremely rare.

PMID- 8553313
TI  - Control and prevention of tuberculosis in the UK.

PMID- 8553315
TI  - [Compulsory blood transfusion].

PMID- 8553314
TI  - Non-invasive mechanical ventilation in acute respiratory failure.

PMID- 8553316
TI  - [Who should conduct abortion counseling?].

PMID- 8553317
TI  - [Who should manage abortion counseling?].

PMID- 8553318
TI  - [On co-authors and pathologists].

PMID- 8553319
TI  - [Failing fight against AIDS].

PMID- 8553320
TI  - [False positive tests for sexually transmitted Chlamydia trachomatis infections].

PMID- 8553321
TI  - [When the patient does not hear].

PMID- 8553322
TI  - [Treatment of hyperlipidemia].

PMID- 8553323
TI  - [Inappropriate public relation drive concerning the treatment of basalioma at the
      Norwegian Radium Hospital].

PMID- 8553324
TI  - [Perinatal committees' obligation to inform].

PMID- 8553325
TI  - [Overuse of albumin].

PMID- 8553326
TI  - [The P-pill controversy--again!].

PMID- 8553327
TI  - [Happy ending... News on telomeres and telomerase].

PMID- 8553328
TI  - [Liver transplantation].

PMID- 8553329
TI  - [Liver transplantation in Norway. Results after 10 years and 114
      transplantations].
AB  - A total of 114 liver transplantations were performed in 106 patients in Norway
      during 1984-1994. Survival after one year was 65% and after three years 57%. The
      most frequent causes of death were infections and rejections. The survival rate
      improved considerably during the period, and after 1990 the 1 year survival was
      70%. Approximately 2/3 of the patients return to work or education. Very few
      patients die later than 12 months after the transplantation. The most frequent
      indications were primary biliary cirrhosis, metabolic liver disease, primary
      sclerosing cholangitis, autoimmune cirrhosis and fulminant liver failure. The
      number of liver transplantations (approximately 4 per million inhabitants) is
      lower in Norway than in the other Nordic countries. The number should be
      increased to 7-8 per million inhabitants.

PMID- 8553330
TI  - [Quality of hemoglobin and glucose analysis in general practice. Results from the
      NOKLUS (Norwegian Health Authority) surveys 1994].
AB  - In 1992 the Norwegian health authorities and the Norwegian Medical Association
      initiated a joint project to secure the quality of laboratory analyses performed
      in primary health care. Two coordinated activities were established: in each of
      the 19 Norwegian counties a medical laboratory adviser was engaged, linked to the
      central clinical chemistry laboratory in that county. These advisers assist
      general practitioners and primary care specialists in securing the quality of
      laboratory procedures performed on their own premises. In addition, a Norwegian
      centre for external quality assurance in primary care (Norwegian abbreviation
      NOKLUS) was established. In 1994 NOKLUS had about 1,600 participants (comprising
      95% of the relevant general and specialist practices). Tolerated limits are based
      on target intervals combined with a percentage tolerated deviation. Fresh
      material is used for haemoglobin, and target values are determined by two
      independent laboratories using the reference method. The article describes the
      results of the surveys of glucose and haemoglobin tests in 1994.

PMID- 8553331
TI  - [Reduced blood utilization in hip arthroplasty. Introduction of a blood
      preservation program].
AB  - In spring 1992 a blood conservation programme was established at Nordland Central
      Hospital with emphasis on indications for blood transfusion and intraoperative
      blood salvage (cell-saver). Medical records from all patients who underwent hip
      arthroplasty during the period 1 June 1991 to 28 February 1994 were examined.
      Mean transfusion of homologous SAGMAN-blood (bank blood) was substantially
      reduced during the period: for total prosthesis (n = 192) from 2.6 to 1.1 units
      per operation (p < 0.0001) and for hemiprosthesis (n = 66) from 3.1 to 0.9 units
      per operation (p = 0.0202). The percentage of patients in each of these two
      groups who did not receive blood transfusion at all increased from 18 to 61 in
      the first group (p < 0.0001) and from 24 to 65 (p = 0.0202) in the second. The
      substantial reduction of bank blood transfusion in this material conforms with
      current international transfusion guidelines. A particular benefit, considering
      the risk of transfusing contagious blood, is the marked increase in the number of
      patients who did not receive any blood product at all.

PMID- 8553332
TI  - [Maternal blood group 0 as a risk factor of neonatal hyperbilirubinemia requiring
      treatment].
AB  - The present prospective study indicates that children of mothers with blood group
      O run a double risk of hyperbilirubinemia requiring treatment as compared to
      children of mothers of blood group A, and 5-10 times increased risk of needing
      exchange transfusion. The most frequent cause of need for exchange transfusion
      was ABO-incompatibility between mother and child. A positive direct antiglobulin
      reaction in an ABO-incompatible child in need of treatment doubles the risk of
      exchange transfusion being required. Blood group O in the mother should be
      considered to be an independent risk factor for the child, and O-pregnant women
      should be ABO-grouped for this reason.

PMID- 8553333
TI  - [Effect of 1-alpha blockader on maximal oxygen consumption and physical endurance
      in hypertensive men].
AB  - The effect of alpha 1 adrenoceptor blockade (doxazosin, 4 mg daily) on maximal
      oxygen uptake (VO2 max) and physical endurance capacity in 16 mildly
      hypertensive, athletic men was investigated in a randomized, placebo-controlled,
      double-blind, two-period of 4 weeks, cross-over study. The maximal work load
      obtained during graded bicycle ergometer exercise and the VO2 max were reduced by
      16 +/- 3 W (mean +/- SE) and 3 +/- 1 ml x kg-1 x min-1 on doxazosin (p < 0.001
      for both), and the running time on 5000 m track increased by 43 +/- 12 sec (p <
      0.05). Thus, alpha 1-blockade moderately reduces VO2 max and physical endurance
      capacity in mildly hypertensive athletic men. However, lower systolic blood
      pressure (9 +/- 4 mm Hg, p < 0.05) immediately after running, and unchanged heart
      rate suggest a safer performance of exercise.

PMID- 8553334
TI  - [Bilateral intra-patellar tendon rupture in a previously healthy woman].
AB  - Bilateral infrapatellar tendon rupture is a relatively rare injury. We describe
      the case of a 32 year old woman who stumbled and sustained a bilateral
      infrapatellar tendon rupture while jogging. In our opinion, this represents an
      unusual mechanism of injury, and we also find it unusual that it was a bilateral
      injury in an otherwise healthy patient. Diagnosis was confirmed by surgical
      exploration eight days after admission to hospital. Despite repeated clinical, X
      ray and ultrasound examinations, the diagnosis was delayed since we initially did
      not consider the trauma adequate to cause such an extensive injury. The diagnosis
      of patella tendon rupture should be based on careful consideration of the history
      of the injury and thorough clinical examination. X-ray and ultrasound can be of
      diagnostic help.

PMID- 8553335
TI  - [Psychiatric group supervision in general practice. A project evaluated by group
      focusing].
AB  - A group supervision project in psychiatry in general practice was established in
      1992. The aims were to increase competence and interest in psychiatry and to
      contribute to a supervision model in psychiatry among general practitioners in a
      sparsely populated area. The group leader, who was a psychiatrist with competence
      in group analysis met with seven physicians for a three hour evening meeting once
      a month over a period of two years. The meetings were structured with a planned
      session at the beginning followed by a more open session. A focus group approach
      was used as the evaluation method. This method showed its usefulness in enabling
      the group to adjust its structure after an evaluation conducted after one year
      had passed and the conclusion at the end of the project period was: Group
      supervision can contribute to increased competence in psychiatry among general
      practitioners. It seems to increase the doctors' confidence and endurance in
      relation to psychiatric problems in family practice and provides an important
      opportunity to share difficult experiences with colleagues.

PMID- 8553336
TI  - [The vomeronasal organ--a rediscovered sensory organ].
AB  - The authors review the function and anatomy of the vomeronasal organ (organ of
      Jacobson), a chemosensory organ situated in the nose. In mammals, stimulation of
      the vomeronasal organ induces sexual behaviour and changes the hormonal status of
      males and females. Impairment of the vomeronasal organ in rats disrupts both the
      females' ultrasound calling during oestrus and their maternal behaviour.
      Stimulation of the vomeronasal organ promotes sexual maturation of juvenile
      females and induces abortion and production of pheromones. Earlier on, the
      vomeronasal organ in man was believed to be present only at the foetal stage; in
      1991 its presence was reestablished in adults. Electrophysiological studies show
      that the vomeronasal organ of man is stimulated by steroids found in human skin.
      The physiological properties of the receptor cells of the vomeronasal organ are
      different from those of the olfactory organ.

PMID- 8553337
TI  - [Transanal endoscopic microsurgery].
AB  - Transanal endoscopic microsurgery was introduced by Buess and co-workers in 1984
      for transanal removal of tumours up to 20 cm above anus. In the present study, 18
      transmural and two mucosal resections were performed for rectal adenomas (16) and
      early rectal cancer (4). Median operation time was 85 minutes (55-140 minutes)
      and the median postoperative stay in hospital was 3 days (1-5). All tumours were
      removed radically and in none was there tumour involvement of the resection
      margin. There were no serious complications. After a median observation time of
      10 months (1-17 months) there have been no recurrences. Functional results are
      excellent; none of the patients have developed incontinence. It is concluded that
      transanal endoscopic microsurgery (TEM) is an adequate method for removal of
      benign rectal tumours and, in selected cases, early rectal cancer.

PMID- 8553338
TI  - [Changing the use of albumin at the Oslo hospital].
AB  - An increasing demand for albumin in Oslo hospitals in the early 1990s instigated
      measures to reduce its use. During the autumn of 1993 a letter was sent to all
      doctors at Ulleval hospital informing them about the lack of documentation that
      albumin supplementation has a positive effect on outcome in critically ill with
      an albumin concentration of more than 20 g/l. In May 1994 the blood bank at
      Ulleval hospital stopped supplying 4% albumin solutions. A 20% reduction in use
      of albumin was observed after the letter of information, followed by a 50%
      reduction after the 4% solution was withdrawn. It is concluded that greater
      awareness of lack of information about the effects of albumin in critically ill
      patients has led to a more restrictive use of albumin. During the same period the
      use of polygeline increased, leading to the assumption that colloids other than
      albumin are being used for volume substitution.

PMID- 8553339
TI  - [Perioperative and postoperative normovolemic anemia. Physiological compensation,
      monitoring and risk evaluation].
AB  - We accept increasingly lower haemoglobin concentrations in order to avoid
      erythrocyte transfusions in surgical patients. Knowledge about the physiological
      adaptation to anaemia, and how this is affected by disease and anaesthesia, are
      necessary in order to foresee when compensation may be inadequate. Only a few
      methods are available at present for monitoring tissue oxygenation i.e. mixed
      venous oxygen saturation, systemic lactacidosis and ECG. In acute haemodilution,
      cardiac output increases by about 30%, mainly because of a drop in peripheral
      resistance. Increased contractility and heart rate may contribute to the
      hyperdynamic circulation and elevate myocardial oxygen demand. In acute anaemia
      the maximal oxygen extraction ratio in humans is approximately 0.5. Erythrocyte
      transfusion carries a small, but not negligible risk of infectious disease
      transmission and immunological incompatibility. Whether allogen transfusions
      increase the rate of postoperative infections and recurrence of cancer is still a
      debated issue. The low rate of complications associated with erythrocyte
      transfusions indicates that the margins of safety should not be too narrow, and
      that the transfusion trigger should be individualized between 5 and 10 g/100 ml.

PMID- 8553340
TI  - [Status of ongoing controlled clinical trials on hypertension].
AB  - Antihypertensive treatment with diuretics and/or beta-blockers lowers stroke and
      coronary heart disease morbidity and mortality. However, although the newer
      antihypertensives induce effective control of blood pressure and regression of
      hypertensive organ damage, it has not been proven whether they reduce mortality.
      Ongoing clinical trials such as STOP II, CAPPP, NORDIL, INSIGHT, ALLHAT and LIFE
      test whether antihypertensive regimens with ACE-inhibitor, calcium-blocker, alpha
      blocker and Angiotensin II-antagonist are equally good or possibly even better
      than diuretics and beta-blockers in preventing cardiovascular complications. The
      HOT trial clarifies how much the diastolic blood pressure should be lowered, and
      whether a small dose of aspirin has a protective effect when combined with
      optimal control of blood pressure. These studies should give better guidelines
      for the treatment of hypertension.

PMID- 8553341
TI  - [Laboratory operations in general practice--where do we stand, concerning quality
      assurance projects?].
AB  - In 1992 a project was started by the Norwegian Medical Association to secure the
      quality of laboratory work performed on physicians' own premises in Norway. The
      project is now well established in all 19 counties and more than 90% of the
      practices participate on a voluntary basis. In each county a central clinical
      chemistry laboratory with a specially engaged laboratory adviser is responsible
      for assisting the general practitioners and specialists with the laboratory work
      performed on their own premises. The assistance includes visits, telephone
      contacts and education courses. An external quality control scheme is carried out
      by a national centre, which distributes samples of unknown concentrations to all
      the participants. The whole project is coordinated by a steering committee, which
      arranges national meetings annually. Working groups have been appointed to
      elucidate more complicated and time-consuming subjects, such as guidelines for
      internal quality control, evaluation of equipment and education programmes. A set
      of written manuals for all kinds of working procedures has recently been prepared
      and adjusted individually to each physician's premises.

PMID- 8553342
TI  - [Increasing use of cesarean section, even in developing countries].
AB  - At Kaziba hospital in rural Zaire, the frequency of deliveries by Caesarean
      section rose from 6.2% in 1971 to 12% in 1992, and the fraction of repeated
      sections rose from 17% to 49%. During the same period, the overall maternal
      mortality decreased from 0.3% to 0.12%, and deaths connected with Caesarean
      section from 3.2% to 0.7%, but still the risk of dying remained 13 times higher
      for births by Caesarean section compared with vaginal deliveries. The frequency
      of vacuum deliveries was halved during the period, and mean birth weight
      decreased by about 100 g. Perinatal mortality remained at about 2%. Among 760
      Caesarean sections performed in the years 1991 and 1992, 93% were emergency
      cases. Spinal anesthesia was used in 97%, and blood transfusion was given to 4%
      of the women. The main indications were mechanical (30%), previous Caesarean
      section (20%), foetal asphyxia (19%), and suspected uterine rupture (10%).
      Uterine rupture was verified in 37 cases (4.9%), of which 27 were Caesarean scar
      ruptures. 259 of the operations were performed by a nurse or a dentist.
      Operations carried out by persons other than physicians were complicated by wound
      infections at a higher rate (20.8%) than those carried out by experienced doctors
      (11.2%). In areas with a poorly developed health system, a high rate of Caesarean
      section represents a hazard to maternal health. The need for knowledge about
      alternative methods like vaginal extraction, symphyseotomy and active management
      of labour is underlined.

PMID- 8553343
TI  - [Is liver transplantation a therapeutic possibility of low priority in Norway?].
AB  - The number of orthotopic liver transplantations per year in Norway is smaller
      than in other countries of Northern Europe. Relatively fewer liver
      transplantations are performed both in the case of accepted indications such as
      primary biliary cirrhosis and acute liver failure, and for more arguable
      indications like post viral cirrhosis and alcoholic liver disease. The authors
      discuss priorities in health care in Norway. The efficacy of liver
      transplantation for selected groups of patients is compared with the efficacy of
      bone marrow transplantation for another selected group of patients. If
      indications and activity of bone marrow transplantation depict the threshold of
      prioritization, then more patients with chronic liver disease should be offered
      liver transplantation as therapy.

PMID- 8553344
TI  - [Calcium antagonists in the treatment of hypertension and heart failure. A
      comment to recently published results of clinical trials].
AB  - Several studies have been published recently on the effect of calcium-antagonists
      in the treatment of hypertension and heart failure. Except for an American case
      control study, in which negative results may have been caused by selection bias,
      other studies show that calcium-antagonists have a positive effect. They appear
      to reduce cardiovascular complications, lower mortality and slow down the
      progression of atherosclerosis. However, large trials of adequate design and
      force are in progress (STOP II, NORDIL, HOT, INSIGHT, ALLHAT). It is hoped that
      the results of these trials will clarify whether calcium-antagonist are warranted
      in the treatment of hypertension and associated cardiovascular disease.

PMID- 8553345
TI  - [Ryegrass cramps in horses].
AB  - CASE STUDY: To elaborate the diagnosis of rye-grass intoxication in a stallion
      demonstrating a neurotoxic syndrome characterized by ataxia and incoordination, a
      number of diagnostic tests were performed. Results of both, blood chemistry and
      haematology gave no indication for organ-specific or systemic lesions. Chemical
      analysis of the hay fed to the horse revealed the presence of the mycotoxin
      lolitrem B in concentrations consistent with those described in sheep and cattle
      with similar symptoms. Thus, it was concluded that the animals demonstrated the
      rye-grass-stagger(RGS)-syndrome.

PMID- 8553346
TI  - [3 cases of an oral eosinophilic granuloma in Siberian huskies].

PMID- 8553347
TI  - [Publication decisions of the Veterinary Disciplinary Tribunal concerning Article
      16, 3rd paragraph, of the Law on Practicing Veterinary Medicine 1990. The
      Veterinary Disciplinary Tribunal].

PMID- 8553348
TI  - [Study on the presence of Borrelia burgdorferi in deer and ticks in 3 areas of
      The Netherlands].

PMID- 8553349
TI  - [Electronic identification companion animals. 'Be sensible and wait!'].

PMID- 8553350
TI  - Frequent hard physical activity lowered serum beta-carotene level in a population
      study of a rural city of Japan.
AB  - To determine the effect of physical activity on serum beta-carotene, we analyzed
      data about life styles including 3-day food records and blood samples collected
      from 57 men and 74 women in a rural city of Japan. Physical activity was asked as
      mean frequency of hard physical activities per week last year. A declining trend
      in serum beta-carotene was observed with increasing frequency of hard physical
      activities in men. In multiple regression analyses, the frequency of hard
      physical activities showed a negative partial correlation coefficient (r = -0.38,
      p = 0.007) with serum beta-carotene in men when controlled by age, BMI (body mass
      index), dietary factors (carotene intake, alcohol consumption and vitamin
      supplements use), smoking status, serum total cholesterol and serum
      triglycerides. These results suggest that frequent hard physical activity
      decreases serum beta-carotene especially in men.

PMID- 8553351
TI  - A radioimmunometric assay for urinary alpha 2-macroglobulin.
AB  - To measure urinary alpha 2-macroglobulin levels, a sensitive radioimmunometric
      assay was established. The least detectable level of this assay was 225 pg/ml. A
      linear correlation between alpha 2-macroglobulin levels and serial dilution of
      urine samples was found. Western blot analysis and study on column chromatography
      revealed that the molecular weight of alpha 2-macroglobulin in urine was
      identical to that of serum alpha 2-macroglobulin. The findings suggested that
      urinary substance detected by the present assay was truly alpha 2-macroglobulin.
      Timed overnight urine samples from 49 diabetic patients with retinopathy and 20
      healthy controls were measured by the present assay. Patients were classified as
      Albustix-negative and Albustix-positive patients. The highest urinary alpha 2
      macroglobulin excretion rates (alpha 2-MER) was found in Albustix-positive
      patients followed by Albustix-negative patients and the healthy controls. In view
      of the fact that the stroke radius of alpha 2-macroglobulin (88A) is larger than
      that of the restrictive pore (56A), the present finding suggests that leakage of
      alpha 2-macroglobulin in urine may be induced by defect of non-discriminatory
      pores in the glomerular basement membrane proposed by Deen and colleagues.

PMID- 8553352
TI  - Development of an apparatus to measure plasma colloid osmotic pressure mounted on
      the extracorporeal hemodialysis circuit.
AB  - We newly developed an apparatus to measure colloid osmotic pressure (COP) of
      blood plasma continuously by hemodialysis (HD) or extracorporeal ultrafiltration
      method (ECUM) without any invasive procedure or blood sampling. The COP value
      measured by this apparatus highly correlated with the COP value calculated from
      the concentration of total protein of blood plasma (TP) sampled simultaneously (y
      = 21.182 + 0.96256x, r2 = 0.911). Measurement of the COP with this apparatus
      seems to be reliable.

PMID- 8553353
TI  - Mild to moderate pulmonary valvular stenosis in infant sometimes improves to the
      condition unnecessary to do PTPV: Doppler echocardiographic observation.
AB  - The purpose of this study is to clarify the natural history of the valvular
      pulmonary stenosis (PS) from the standpoint of the indication for percutaneous
      transvenous pulmonary valvuloplasty (PTPV). We retrospectively analyzed age
      dependent changes of the peak velocity in the pulmonary artery (peak V) using
      Doppler echocardiography (Doppler), and some other echocardiographic and clinical
      findings in 55 children with mild to moderate PS. Groups A, B, and C consisted of
      those who had peak V above 3.54 m/sec, between 3.54 and 2.74 m/sec, and less than
      2.74 m/sec, respectively. Peak V of 42 patients who had the first Doppler study
      before 1 year of age decreased from 2.61 +/- 0.66 to 2.27 +/- 0. 80 m/sec (p <
      0.01). One infant in group A, that initially included 3 children, has improved to
      group B. Among the 15 patients in group B, one patient deteriorated to group A,
      and peak V of 10 infants reduced to less than 2.74 m/sec. In group C, peak V of 2
      infants increased above 2.74 m/sec. Other than age at the first examination, we
      could not find specific indications that could predict the reduction of peak V.
      Mild to moderate PS younger than 1 year of age sometimes markedly improves; the
      invasive procedure of PTPV may not be necessary in non-critical infant patients
      with mild to moderate PS.

PMID- 8553354
TI  - A screening system for antiviral compounds against herpes simplex virus type 1
      using the MTT method with L929 cells.
AB  - We developed the improved MTT assay system for in vitro evaluation of anti-HSV-1
      agents using L929 cells derived from mouse connective tissue. This assay system
      provides results in 4 days using a 96-well microplate. The EC50 values of several
      anti-HSV agents (ACV, BVaraU, and others) were found to be similar to those
      obtained by the plaque reduction method using MRC-5 cells. The present MTT assay
      is rapid, accurate, and may be useful as an automatic screening system for
      evaluation of anti-HSV-1 compounds.

PMID- 8553355
TI  - Cystic adventitial disease of the popliteal artery--a case of young boy.
AB  - Cystic adventitial disease (CAD) of the popliteal artery (PA) is rare but one of
      the well-recognized causes of intermittent claudication. Now more than 200 case
      reports are available in the world, but there are only 6 cases younger than 15
      years old. In this paper, we report a case of 14-year-old boy with CAD of the PA
      found by intermittent claudication. On examination, the pulses were not palpable
      below the right popliteal artery, and the angiography demonstrated about 1.5 cm
      long obstruction of the right PA. We operated a resection of a cyst with artery,
      and replaced the autovein graft (V. saphena magna). Cyst contained mucoid
      degeneration-like ganglion. Two weeks after operation, the angiography showed no
      stenotic lesion, and follow-up at 4 years showed no symptoms.

PMID- 8553356
TI  - A case of glycogen storage disease type III (glycogen debranching enzyme
      deficiency) with liver cirrhosis and hypertrophic cardiomyopathy.
AB  - We present a 26-year-old woman with glycogen storage disease type III
      (debranching enzyme deficiency) complicated with liver cirrhosis and hypertrophic
      cardiomyopathy. Glycogen debranching enzyme has two catalytic sites, oligo-1,4,
      1,4- glucantransferase (EC 2.4.1.25) and amylo-1,6-glucosidase (EC 3.2.1.33).
      Variability in the clinical phenotype could be a function of the involvement of
      one or other catalytic site, or differences in tissue expression of the defective
      enzyme, or both. We hypothesize that some subtypes of glycogen storage disease
      (GSD) type III may cause liver cirrhosis as seen in GSD type IV due to the
      accumulation of glycogen of abnormal structure.

PMID- 8553357
TI  - A case of cutaneous anthrax.
AB  - A 63-year-old man developed black crusts on the parietal scalp that showed mixed
      infections of dermatophytes and Bacillus anthracis on culture. The lesions
      improved with bifonazole, griseofulvin and bacampicillin hydrochloride. Although
      cutaneous anthrax is now a very rare disease, the mortality is high in untreated
      cases. If a patient has black crusts, anthrax should be differentiated firstly.

PMID- 8553358
TI  - Effects of chelating agents on testicular toxicity in mice caused by acute
      exposure to nickel.
AB  - N-Benzyl-D-glucaminedithiocarbamate (BGD), diethyldithiocarbamate (DDTC),
      dihydroxyethyldithiocarbamate (DHED), trans-1,2-cyclohexanediamine N,N,N',N'
      tetraacetic acid (CDTA), and meso-2,3-dimercaptosuccinic acid (DMSA) were studied
      for their protective effects against the testicular toxicity in mice induced by
      acute exposure to nickel (Ni). Mice were injected intraperitoneally with NiCl2 (5
      mgNi/kg) and 30 min or 24 h later, they were injected intraperitoneally with
      chelating agents (400 mumol/kg). Ni injection increased lipid peroxidation and
      concentrations of Ca and Fe in the testes, liver, and kidney, and decreased the
      testicular weight and the fertility rate. At 30 min after Ni treatment, the
      chelating agents other than CDTA effectively depressed Ni concentration in the
      testes. At 24 h after Ni treatment, DMSA, BGD, and DDTC were effective in
      mobilizing Ni from the testes. DMSA, BGD, and CDTA significantly prevented the
      increase in the lipid peroxidation, the increase in the concentrations of Ca and
      Fe in the testes, liver, and kidney, and the decrease in the fertility rate
      caused by Ni injection. Treatment with DMSA or BGD was more effective than that
      with the others in decreasing the testicular Ni concentration, resulting in
      effective protection against Ni-induced testicular damage.

PMID- 8553359
TI  - Selenium distribution and metabolic profile in relation to nutritional selenium
      status in rats.
AB  - The disposition of selenium (Se) was investigated in Wistar rats of various Se
      status after an intravenous injection of 82Se-selenite. Various fractions of
      plasma, urine, and cytosols from liver and kidney were separated by high
      performance liquid chromatography (HPLC), coupled with an inductively coupled
      argon plasma-mass spectrometry (ICP-MS). The technique allowed simultaneous
      differentiation of the fate of injected and endogenous Se, and if it was
      influenced by the previous Se burden in the tissues. A broad Se-peak from plasma
      was resolved in two fractions by assessing the m/z 82/78 ratios. Urinary profiles
      indicated that the metabolism of Se was dose-dependent; monomethylselenol being
      the primary metabolite of Se in untreated animals, whereas noticeable amount of
      trimethylselenonium ion was detected after the injection of 82Se. Liver and
      kidney cytosols contained complex Se-enriched fractions, a positive
      identification of which was not done in this study. In most cases, the enrichment
      of tissue fractions with the stable isotope was altered by the dietary Se levels,
      the isotope nevertheless was exchanged with the endogenous Se in various
      macromolecules to a varying degree.

PMID- 8553360
TI  - Oxidative stress and cytotoxicity of 4-(2-thienyl)butyric acid in isolated rat
      renal proximal tubular and distal tubular cells.
AB  - Relative cytotoxicity and mechanism of action of thiophenes were investigated in
      suspensions of freshly isolated renal proximal tubular (PT) and distal tubular
      (DT) cells using 4-(2-thienyl)butyric acid (TByA) as a model compound. TByA
      produced significantly greater time- and concentration-dependent cytotoxicity, as
      assessed by release of lactate dehydrogenase, in PT cells than in DT cells.
      Greater intracellular accumulation of TByA in PT cells may play a role in the
      enhanced cytotoxicity. Pretreatment of cells with alpha-tocopherol partially
      protected both PT and DT cells from TByA-induced cytotoxicity, suggesting that
      oxidative stress may be involved in the mechanism of action. In contrast,
      pretreatment of cells with SKF-525A, an inhibitor of cytochrome P-450, enhanced
      TByA-induced cytotoxicity in both cell populations, particularly in DT cells.
      Enhanced accumulation of TByA in SKF-525A-pretreated cells and additional
      bioactivation mechanisms may be responsible for the enhancement of cytotoxicity.
      TByA produced GSH oxidation, lipid peroxidation, and inhibition of cellular
      respiration in both cell populations, supporting involvement of oxidative stress
      and mitochondrial dysfunction in cytotoxicity.

PMID- 8553361
TI  - Structure activity relationships in skin sensitization using the murine local
      lymph node assay.
AB  - Murine local lymph assay node data for 106 chemicals are listed. Among these, 73
      are active in the assay indicating their potential as skin sensitizing agents.
      Broad structure activity relationships (SAR) are suggested based on the
      electrophilic theory of skin sensitization suggested by Landsteiner and Jacobs in
      1936, and elaborated by Dupuis and Benezra in 1982. Eight classes of agent are
      discerned; electrophiles, potential electrophiles after metabolism, Michael
      reactive agents, benzoylating agents, ionic chemicals and miscellaneous agents.
      The electrophilic theory cannot at present fully explain the activity of agents
      in the last two classes. That fact will hopefully focus research into their mode
      of action. Some chemicals fit equally into more than one class, and such agents
      are entered into the several classes in order not to bias the analysis. Attention
      is given to why not all chemicals of a class are active in the assay. It is
      concluded that a combination of inappropriate lipophilicity, molecular size and
      metabolic detoxification are responsible for these inactivities. Given a
      sufficient number of analogues tested within each class it should be possible
      eventually to predict with accuracy the skin sensitizing potential of new members
      of the class. However, the present analysis is qualitative, not quantitative.
      Finally, the parallelism between sensitizing potential and mutagenic potential
      for chemicals is explored further.

PMID- 8553362
TI  - No evidence for emergence of autoreactive V beta 6+ T cells in Mls-1a mice
      following exposure to a thymotoxic dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - Tolerance to minor lymphocyte stimulatory-1a (Mls-1a) antigens is associated with
      clonal deletion of cells carrying the T cell receptor variable region V beta 6.
      Thymic epithelial cells may contribute to the intrathymic negative selection of
      potentially autoreactive V beta 6+ cells. Because 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) acts on thymic epithelial cells, we hypothesized that it may
      interfere with intrathymic selection processes. In the present study, this was
      addressed by exposing Mls-1a DBA/2 mice to a single thymotoxic dose of TCDD. The
      emergence of V beta 6+ cells in thymus, spleen, and mesenteric lymph nodes was
      investigated during the subsequent recovery of TCDD-induced thymic atrophy. In
      addition, the extrathymic differentiation of T lymphocytes in the liver was
      studied. TCDD exposure resulted in a severe thymic atrophy, and an increase in
      hepatic mononuclear cells. However, we were not able to demonstrate any emergence
      of potentially autoreactive mature V beta 6+ T cells, that differentiated either
      intrathymically or extrathymically, in TCDD-exposed DBA/2 mice.

PMID- 8553363
TI  - Antioxidant defense in rat brain after chronic treatment with anorectic drugs.
AB  - Mazindol (5-hydroxy-5-p-chlorophenyl-2,3-dihydro-5H-imidazo-2,1-a-isoindole)
      although not chemically related to the phenylethylamine group, shows a
      pharmacological profile similar to that of amphetamines. In rats these anorectic
      drugs enhance dopamine (DA) turnover, which is the mechanism that causes
      anorexia. It has been hypothesized that amphetamine causes a long-lasting
      depletion of DA, a decrease of dopaminergic transport pumps and nerve terminal
      degeneration increasing. These actions provide a cellular environment encouraging
      the autoxidation of DA that may lead to lipid peroxidation and neuronal damage.
      Considering that both drugs may cause neuronal damage by oxidative mechanisms,
      this study was conducted to investigate the action of mazindol and
      methamphetamine on brain cell antioxidant defense system and to investigate
      whether animal age is important in the antioxidant response to chronic anorectic
      administration. The activity of superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GPx), as well as the total glutathione (GSH) content in
      brains of rats, were measured. The animals (2 groups with 5 and 18 months old)
      were treated for 5 months (i.p.) with mazindol (10 mg/kg body weight/day),
      methamphetamine (2.5 mg/kg body weight/day) or saline. The results obtained
      showed no differences between SOD, CAT, GPx activities and GSH content in the
      brain of animals treated with saline compared with both drugs, either in 10-month
      or 23-month groups. On the other hand, brain total GSH content of old animals was
      found to be lower than that from young ones, independent of the treatment. SOD
      activity was found to be increased, CAT unchanged and GPx decreased, in the brain
      of old animals, treated with both drugs or saline. These findings led us to
      conclude that the chronic administration of mazindol and methamphetamine have no
      effects on the antioxidant systems studied either in young (10 months) or in old
      (23 months) rats.

PMID- 8553364
TI  - Inhibition of DNA synthesis in primary rat hepatocyte cultures by malachite
      green: a new liver tumor promoter.
AB  - Malachite green (MG), a triarylmethane dye is highly cytotoxic to mammalian cells
      and also acts as a liver tumour-enhancing agent. In view of its industrial
      importance and possible exposure to individuals, MG may pose a potential
      environmental health hazard. The mechanism(s) by which MG enhances DEN-induced
      liver carcinogenesis is still unknown even though growth modulatory effects
      appear to be important in its action. Therefore, we have studied the effect of MG
      on DNA synthesis in primary cultures of normal adult rat hepatocytes maintained
      under fully defined conditions. The rate of DNA synthesis in both untreated and
      hepatocytes treated with epidermal growth factor (10 ng/ml) were inhibited by MG
      at concentrations of 0.025-0.4 micrograms/ml. These inhibitory effects were
      concomitant with an extensive release of lactate dehydrogenase which began after
      24 h. MG inhibited DNA synthesis when added after only 16 h in hepatocytes either
      primed or not primed with EGF, suggesting that the target site may be other than
      the EGF-receptor or EGF-mediated early events involving signal transduction. The
      present study indicates that cytotoxic and mitoinhibitory properties of MG
      possibly play an important role during tumour promotion.

PMID- 8553365
TI  - Thiols metabolism is altered by the herbicides paraquat, dinoseb and 2,4-D: a
      study in isolated hepatocytes.
AB  - This report is an extension and complement of a previous study reporting the
      effect of three herbicides (paraquat, dinoseb and 2,4-D) on cell viability, GSH
      oxidation, NADH and ATP depletion (Arch. Toxicol. 68:24-31, 1994). Here we report
      additional data and findings aimed at a better understanding of the toxicity
      mechanisms induced by these herbicides. Biochemical mechanisms of cytotoxicity
      induced by the herbicides paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride),
      dinoseb (2-sec-butyl-4,6-dinitrophenol) and 2,4-D (2,4-dichlorophenoxyacetic
      acid) were investigated in freshly isolated rat hepatocytes. Herbicide
      metabolism, especially paraquat and 2,4-D, rapidly depletes GSH and protein
      thiols. Paraquat and 2,4-D (1-10 mM) decrease the GSH/GSSG ratio, promote loss of
      protein thiol contents and induce lipid peroxidation. Dinoseb, the most effective
      cytotoxic compound under study (used in concentrations 1000-fold lower than
      paraquat and 2,4-D), had moderate effects upon the GSH/GSSG ratio and lipid
      peroxidation, causing a depletion of protein thiols of about 20%. The results
      indicate that the herbicides paraquat and 2,4-D are hepatotoxic and may induce
      cell death by decreasing cellular GSH/GSSG ratio and protein thiols, and by
      inducing lipid peroxidation. The cytotoxic action of dinoseb is likely to be
      related with the uncoupling of oxidative phosphorylation in mitochondria.
      Therefore, it is likely that liver damage observed during the first phase of
      herbicide-intoxication is related to these metabolic processes.

PMID- 8553366
TI  - Inhibitory effect of cold stress against acetaminophen-induced hepatic injury in
      B6C3F1 and ICR mice.
AB  - The effect of cold stress (at 0 +/- 1 degree C for 3 h) on acetaminophen-induced
      hepatic injury was investigated in B6C3F1 and ICR mice. When acetaminophen (250
      mg/kg) was injected intraperitoneally in B6C3F1 mice, the plasma GPT activity was
      significantly increased by 93 or 107-fold at 6 h or 24 h after the drug
      injection. However, when B6C3F1 mice were exposed to cold stress, the increase in
      plasma GPT activity induced by acetaminophen was significantly inhibited by 53%
      and 44%, respectively. On the other hand, when acetaminophen at the same dose was
      injected in ICR mice, the activity of plasma GPT was increased by 9-fold at 6 h,
      or 16-fold at 24 h after the drug injection. The increased plasma GPT activity
      elicited a significant inhibition of 35% and 36%, respectively, by the exposure
      to cold stress. These results suggest that acetaminophen-induced hepatic injury
      may be blocked by physical stress in mice.

PMID- 8553367
TI  - Increased oxidant resistance of alveolar epithelial type II cells. Isolated from
      rats following repeated exposure to cadmium aerosols.
AB  - Alveolar epithelial type II cells (AEIIC) were isolated from male Lewis rats
      following repeated in vivo cadmium aerosol exposure and were subsequently
      evaluated for their oxidant resistance in vitro. AEIIC from Cd-adapted animals
      removed a greater proportion of hydrogen peroxide from the extracellular milieu
      and incurred less oxidant-induced cytotoxicity than AEIIC from air controls. This
      altered response to oxidants occurred coincident with changes in cellular
      resistance factors. A two-fold increase in glutathione peroxidase activity and a
      1.5-fold increase in the activities of glutathione reductase and catalase were
      observed in Cd-adapted AEIIC compared to control cells. These cells also
      exhibited a dramatic induction of metallothionein (MT), a thiol-rich protein
      known to scavenge free radicals in vitro. MT concentration increased as a
      function of exposure number. MT was localized within the nucleus and cytoplasm of
      AEIIC by immunocytochemical techniques. MT positive cells showed a wide variation
      of MT content, particularly in the nucleus. The biochemical and physiological
      features of these AEIIC may explain, in part, why animals pretreated with Cd
      aerosols develop cross-tolerance to hyperoxia.

PMID- 8553368
TI  - Inhibition of NAD(H)/NADP(H)--requiring enzymes by aurintricarboxylic acid.
AB  - Aurintricarboxylic acid (ATA), an inhibitor of Ca(2+)-dependent endonuclease
      activity, is often used to implicate a role for increased intracellular calcium
      in mechanistic toxicology studies. We report here on the ability of ATA to
      inhibit the activity of several NAD(H)/NADP(H)-requiring enzymes (purified or
      cellular homogenates), including lactic dehydrogenase, alcohol dehydrogenase,
      cytochrome c reductase, ethoxycoumarin o-dealkylase, isocitric dehydrogenase,
      glutathione reductase and glucose-6-phosphate dehydrogenase. These results were
      compared with the ability of ATA to inhibit micrococcal nuclease and rat liver
      Ca(2+)-dependent endonuclease activity in similar incubations. With the exception
      of alcohol dehydrogenase, ATA was a potent inhibitor of each of the purified
      enzymes, with IC50s ranging from 0.5 to 82 microM. In cell homogenates, however,
      ATA was from 10 to 100-fold less potent at inhibiting these enzymes. When
      exogenous protein was added to purified enzyme incubations, the effect of ATA was
      similarly diminished. Our results demonstrate that ATA inhibits a wide range of
      NAD(H)/NADP(H)-requiring enzymes in in vitro incubations using purified enzymes,
      but that the inhibitory effects are markedly reduced in incubations which more
      closely resemble a cellular milieu.

PMID- 8553369
TI  - Role of intracellular Cd2+ in catecholamine release and lethality in PC12 cells.
AB  - To evaluate the role of intracellular Cd2+ in catecholamine release and lethality
      in rat pheochromocytoma (PC12) cells the following results were obtained: [1] the
      presence of Cd2+ intracellularly was demonstrated with the Cd(2+)-sensitive
      fluorescent dye BTC-5N, [2] Cd2+ entry through Ca(2+)-channels was either blocked
      with nifedipine or diltiazem or increased with Bay K8644, [3] Cd2+ entry through
      voltage sensitive Ca2+ channels was related to dopamine release and cell
      lethality, [4] a calmodulin inhibitor protected against Cd2+ toxicity, and [5]
      extracellular Ca2+ concentration, altered prior to Cd2+ exposure, was inversely
      related to dopamine release by Cd2+. The data indicate intracellular effects of
      Cd2+ rather than cell surface actions are primarily involved in neurotransmitter
      release and lethality by toxic levels of Cd2+ in adrenomedullary cells. To
      evaluate the role of intracellular Cd2+ in catecholamine release and lethality in
      rat pheochromocytoma (PC12) cells the following results were obtained: [1] the
      presence of Cd2+ intracellularly was demonstrated with the Cd(2+)-sensitive
      fluorescent dye BTC-5N, [2] Cd2+ entry through Ca(2+)-channels was either blocked
      with nifedipine or diltiazem or increased with Bay K8644, [3] Cd2+ entry through
      voltage sensitive Ca2+ channels was related to dopamine release and cell
      lethality, [4] a calmodulin inhibitor protected against Cd2+ toxicity, and [5]
      extracellular Ca2+ concentration, altered prior to Cd2+ exposure, was inversely
      related to dopamine release by Cd2+. The data indicate intracellular effects of
      Cd2+ rather than cell surface actions are primarily involved in neurotransmitter
      release and lethality by toxic levels of Cd2+ in adrenomedullary cells.

PMID- 8553370
TI  - Loss of mitochondrial membrane potential is not essential to hepatocyte killing
      by allyl alcohol.
AB  - Allyl alcohol-induced LDH leakage from isolated rat hepatocytes was preceded by a
      decrease in rhodmine 123 retention, signifying a loss of mitochondrial membrane
      potential. Addition of dithiothreitol (DTT) prevented the drop in membrane
      potential and completely prevented cell killing by allyl alcohol. In contrast,
      cyclosporin A and trifluoperazine delayed the loss of membrane potential without
      affecting cytolethality. The results indicate that a drop in mitochondrial
      membrane potential is not essential for allyl alcohol lethality. The
      mitochondrial dysfunction produced by allyl alcohol appears to be the consequence
      of an earlier event in the toxicity that is reversible by DTT.

PMID- 8553371
TI  - 2,4-Dichlorophenoxyacetic acid influx is mediated by an active transport system
      in Chinese hamster ovary cells.
AB  - The influx of 2,4-dichlorophenoxyacetic acid (2,4-D) into Chinese hamster ovary
      (CHO) cells was studied. The cells mainly took up but did not metabolize the
      undissociated form of the herbicide. The uptake of 2,4-D was carried out against
      a concentration gradient and was inhibited by sodium azide and dinitrophenol. The
      results presented here show that the herbicide influx was an active, energy
      dependent process. (Na+ + K+)ATPase does not seem to be involved because ouabain,
      an inhibitor of the enzyme, did not affect the 2,4-D uptake.

PMID- 8553372
TI  - Inhibition of tumor necrosis factor activity fails to restore 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-induced suppression of the antibody response
      to sheep red blood cells.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) immunotoxicity is characterized in
      part by a profound suppression in T cell-dependent antibody production to sheep
      red blood cells (SRBC); however the mechanisms involved in antibody suppression
      are not fully understood. Recent studies from several different laboratories have
      suggested that increased tumor necrosis factor (TNF) activity may mediate some of
      the toxicity associated with TCDD exposure. The current studies were designed to
      evaluate the role TNF plays in TCDD-induced suppression of the antibody response.
      We examined the effects of exogenous TNF alpha and the effects of blocking TNF
      activity with a soluble TNF receptor (rhuTNFR:Fc) on antibody production in
      control and TCDD exposed C57B1/6 mice. Results indicate that under certain
      conditions, increased TNF can suppress antibody production to SRBC, but TNF does
      not appear to mediate TCDD-induced antibody suppression.

PMID- 8553373
TI  - Use of Mishell-Dutton culture for the detection of the immunosuppressive effect
      of iron-containing compounds.
AB  - Mishell-Dutton culture, known as an in vitro model for the evaluation of the
      humoral immune response of mice spleen cells to sheep red blood cells (SRBC), was
      used to study the immunosuppressive effect of iron-containing compounds. This
      response was indicated by the number of antibody forming cell (AFC) per million
      nucleated cells. Ferrous sulfate and ferric citrate (0.1 mM), when continuously
      present in Mishell-Dutton culture, significantly decreased the SRBC AFC response
      by approximately 63% and 86% of the control values, respectively. Ferric citrate,
      preincubated (24 h) with spleen cells and followed by lavage, significantly
      decreased the SRBC AFC response by approximately 54% of the control values.
      Primary and iron-treated coal, in concentrations ranging from 40 micrograms.ml-1
      to 120 micrograms.ml-1, significantly decreased the SRBC AFC response when
      continuously present in Mishell-Dutton culture. Iron-treated coal, suppressed
      this response, in dose-dependent amounts, to a greater extent than did the
      primary coal:73% versus 54% at 120 micrograms.ml-1. We concluded that Mishell
      Dutton culture is suitable for studying the immunotoxicity of iron and these
      results may contribute to explain a decrease of host resistance against parasitic
      and bacterial infection in workers exposed to iron.

PMID- 8553374
TI  - Influence of cadmium ions on endothelin-1 binding and calcium signaling in rat
      glioma C6 cells.
AB  - Cadmium ions did not influence the binding of endothelin-1 (ET-1) to its receptor
      on the surface of rat glioma C6 and rat aorta A10 cells. This was studied (a) by
      the binding of 1251-ET-1 to intact cells in the absence or presence of cadmium
      (Cd2+) and (b) by analysis of the receptor/ET-1 complex after crosslinking with
      disuccinimidyl suberate (DSS) or ethylene glycol-bis-(succinimidyl succinate)
      (EGS) on SDS PAGE. Using Fura-2 and Quin-2 loaded C6 rat glioma cells, it was
      shown that Cd2+ ions strongly interfered with the ET-1 induced Ca(2+)-influx in
      C6 glioma cells (IC50 approximately 10 microM).

PMID- 8553375
TI  - Modulation of protein kinase C by heavy metals.
AB  - Protein kinase C (PKC) regulates a variety of intracellular and extracellular
      signals across the neuronal membrane. PKC requires calcium and phospholipid,
      particularly phosphatidylserine (PS) for its activation. The data indicates that
      mercury (Hg), lead (Pb) and methyl mercury (CH3Hg) in vitro inhibited the PKC
      activity at micromolar concentrations in a concentration-dependent manner with
      IC50 values of 1.5, 2.12 and 0.22 microM, respectively. The IC50 values indicate
      that CH3Hg was more potent in inhibiting the enzyme activity than Hg or Pb. The
      basal PKC activity was also inhibited by Pb or Hg. However, the PS-stimulated PKC
      activity was more sensitive to Pb or Hg than the basal enzyme. The phorbol ester
      binding to PKC was also found to be inhibited by micromolar concentrations of
      these metals in vitro. Hg and CH3Hg were more potent inhibitors of phorbol ester
      binding than Pb. Dithiothreitol (DTT), a dithiol, but not glutathione (GSH) a
      monothiol, protected the activities of both PS-stimulated and basal PKC from
      metal-inhibition in a concentration-dependent manner. The present study suggests
      that the dithiols but not monothiols effectively protect metal-inhibited activity
      of PKC in rat brain.

PMID- 8553376
TI  - Topical exposure to chlordane reduces the contact hypersensitivity response to
      oxazolone in BALB/c mice.
AB  - Previous studies have shown that prenatal exposure to the organochlorine
      pesticide chlordane significantly decreases the ear swelling response to the
      contact allergen oxazolone in BALB/c mice. Alterations of macrophage function in
      the efferent arm of the contact hypersensitivity response have also been
      reported. In the current study, chlordane was applied topically and the effects
      of oxazolone-induced contact hypersensitivity were determined. Initially, the
      reduction in oxazolone-induced ear swelling in topically-exposed female BALB/c
      mice was compared to 30-day-old BALB/c female mice exposed prenatally to
      chlordane. Prenatal chlordane exposure induced a 36% reduction in ear swelling
      compared to a 60% reduction following topical treatment at the challenge phase.
      Topically-applied chlordane also reduced the oxazolone-induced ear swelling by
      40% when applied at sensitization. When applied at both sensitization and
      challenge, ear swelling was reduced by 71%. In a time-course study, it was
      determined that chlordane must be applied at the time of sensitization, challenge
      or both or within 1 h post-challenge to significantly reduce ear swelling. A dose
      response study showed that the lowest concentration of chlordane resulting in a
      significantly reduced ear swelling response was 20 micrograms per ear.

PMID- 8553377
TI  - Comparison of propylene oxide and epichlorohydrin effects in two transformation
      tests (C3H/10T1/2 and SHE cells).
AB  - The neoplastic cell transformation induced by propylene oxide (PO) and
      epichlorohydrin (ECH) was studied in two in vitro assays, mouse embryo
      fibroblasts (C3H/10T1/2) and Syrian hamster embryo (SHE) cells. In C3H/10T1/2
      cells treated with PO (2.5-10 mM), the transformation frequencies were enhanced
      about 2-4 times in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA),
      compared with the transformation frequencies in the absence of TPA. In SHE cells,
      an even higher increase (about 6-9 times) was reached at concentrations of 2.5-20
      mM. The presence of TPA strongly influenced the ability of ECH to induce the
      morphological transformation at low-moderate concentrations (0.25-1 mM). At the
      highest concentrations applied, 1 mM in C3H/10T1/2 cells and 0.5 mM in SHE cells,
      41- and 4-fold increases, respectively, were observed. In C3H/10T1/2 cells, the
      rad-equivalence (rad/mMh) of PO and ECH in the presence of TPA was calculated to
      be 36 +/- 8 and 296 +/- 65 (mean +/- S.E.), respectively.

PMID- 8553378
TI  - Metabolism of amiodarone following intratracheal instillation in hamsters.
AB  - Intratracheal instillation of the antiarrhythmic drug amiodarone (AD) in hamsters
      is an established animal model of AD-induced pulmonary fibrosis. A metabolite of
      AD, desethylamiodarone (dAD), has also been shown to produce pulmonary fibrosis
      in this model. It was previously reported that following intratracheal
      instillation of AD in hamsters, metabolite could not be detected in lung tissue.
      However, in studies in our laboratory dAD was detected following instillation of
      AD. The goal of the present study was to monitor the distribution of AD and dAD
      to lung and liver within 1 h of AD instillation and to investigate the site of AD
      metabolism. Both AD and dAD were detected in the lung and liver within 5 min of
      AD instillation; lung and liver concentrations of AD and dAD were also quantified
      at 30 and 60 min following AD instillation. Incubation of lung and liver
      microsomes with AD showed that the liver is a probable site of AD metabolism
      following the intratracheal administration of AD to hamsters.

PMID- 8553379
TI  - Dose-dependent suppression of toluene metabolism by isopropyl alcohol and methyl
      ethyl ketone after experimental exposure of rats.
AB  - In order to examine possible suppression of toluene metabolism due to coexposure
      to other solvents, female Wistar rats were exposed for 8 h to toluene alone (at
      50 or 100 ppm), or in combination with either methyl ethyl ketone (at 50, 100,
      200 or 400 ppm) or isopropyl alcohol (at 50, 100, 200, 400, 800 or 1600 ppm).
      Urine samples were collected for 24 h after initiation of each exposure, and
      subjected to analysis for two toluene metabolites, hippuric acid and o-cresol,
      both by HPLC. The excretion of hippuric acid, a major metabolite, was not
      modified when the concentrations of methyl ethyl ketone or isopropyl alcohol were
      low, i.e. 100 ppm or below, whereas it was reduced when methyl ethyl ketone or
      isopropyl alcohol concentrations were twice or more times higher than that of
      toluene. There were no changes in any cases in excretion of o-cresol, a minor
      metabolite. The observation after coexposure to methyl ethyl ketone or isopropyl
      alcohol at low concentration is in line with the negative interaction between
      toluene and methyl ethyl ketone as well as between toluene and isopropyl alcohol
      after occupational exposures at low concentrations. Metabolic interaction may
      take place when the exposure intensity is high, as observed in the present study
      and also after experimental exposure of volunteers to toluene and m-xylene, or
      occupational exposure to benzene and toluene.

PMID- 8553380
TI  - Guanidinoacetic acid (GAA) synthesis in rat tubular suspension as a system for
      evaluating gentamicin (GM) nephrotoxicity.
AB  - Since guanidinoacetic acid (GAA), a precursor of creatine, is synthesized mainly
      in the proximal tubule of the kidney where gentamicin (GM) nephrotoxicity often
      occurs, GM-induced renal cell damage was investigated using GAA synthesis in
      tubular suspension as an indicator. Results obtained were as follows: (1) GAA
      synthesis was significantly suppressed with 1 mM GM; (2) GM-induced decrease in
      GAA synthesis was recognized during incubation longer than 15 min; (3) furosemide
      significantly enhanced the suppression of GAA synthesis by GM. The results
      obtained parallel with those in the whole animal thus making GAA synthesis in
      tubular suspension a valid system for evaluating the GM-induced proximal tubular
      damage.

PMID- 8553381
TI  - Developmental exposure to ozone induces subtle changes in swimming navigation of
      adult mice.
AB  - Following exposure to ozone (O3, 0.6 ppm) from the beginning of neonatal life
      until weaning, adult CD-1 mice were tested in swimming navigation, a sensitive
      indicator for hippocampal damage. Control mice received a sham exposure. All mice
      were tested at 12-13 weeks of age for their ability to find a submerged platform
      in a fixed location (acquisition: 18 trials, six trials per day) and for capacity
      to re-orient towards a new platform position (reversal: 12 trials, six trials per
      day). Exposure to O3 did not produce any significant impairment of swimming
      navigation during the acquisition phase while it slightly increased the swimming
      paths during the last day of the reversal phase. Mice exposed to O3 showed a
      slightly but significantly higher swimming speed during all the days, which was
      unrelated to differences in body weight and to navigational performances.
      Moreover, mice exposed to O3 (with the exception of one animal) had a strong
      tendency to make turns to the left while the controls, independent of sex,
      preferred clockwise turns. Data are discussed with respect to possible
      implications with early CNS and immune alteration leading to behavioral
      asymmetries at adulthood.

PMID- 8553382
TI  - Factors that predict the bleeding risk of cerebral arteriovenous malformations.
AB  - BACKGROUND AND PURPOSE: Arteriovenous malformations (AVMs) have an overall 2% to
      4% annual risk of hemorrhage. The purpose of this study was to determine whether
      specific clinical and radiographic factors predispose AVMs to bleed and to
      predict the bleeding risk for individual AVM patients. METHODS: We reviewed the
      clinical histories and cerebral angiograms of 315 AVM patients who underwent
      stereotactic radiosurgery at our center. One half of the patient data (analysis
      cohort) was used to determine risk factors for bleeding and to construct AVM
      hemorrhage risk groups. These risk groups were then tested with the second half
      of the patient data (test cohort). RESULTS: The mean AVM volume was 4.0 +/- 3.4
      mL (approximate maximum diameter of 2 cm). One hundred ninety-six initial
      hemorrhages occurred in 10,348 patient-years for an annual initial bleed rate of
      1.89%; 44 of these 196 patients had a repeat bleed in 591 patient-years for an
      annual rebleed rate of 7.45%. The overall crude annual hemorrhage rate was 2.40%.
      Multivariate analysis revealed three factors associated with hemorrhage: history
      of a prior bleed (relative risk [RR], 9.09; 95% confidence interval [CI], 5.44 to
      15.19; P < .001), a single draining vein (RR, 1.66; 95% CI, 1.13 to 2.38; P <
      .01), and a diffuse AVM morphology (RR, 1.64; 95% CI, 1.12 to 2.46; P < .01).
      Four AVM hemorrhage risk groups were constructed on the basis of the significant
      factors. The annual rate of bleeding was 0.99% for low-risk AVMs, 2.22% for
      intermediate-low-risk AVMs, 3.72% for intermediate-high-risk AVMs, and 8.94% for
      high-risk AVMs. CONCLUSIONS: Analysis of a large group of AVM patients who
      underwent stereotactic radiosurgery demonstrated that small AVMs have an annual
      hemorrhage risk similar to that of the general AVM population. AVM patients have
      a wide variability of bleeding risk that can be predicted from their clinical
      presentation and the angiographic characteristics of the AVM. The management of
      AVM patients should be based not only on the morbidity of the proposed treatment
      but also those factors that predispose individual patients to either a low or
      high hemorrhage risk.

PMID- 8553383
TI  - Is Marfan syndrome associated with symptomatic intracranial aneurysms?
AB  - BACKGROUND AND PURPOSE: Marfan syndrome is a heritable disorder of connective
      tissue caused by a deficiency of the glycoprotein fibrillin. In several
      publications and neurological textbooks, a relationship between Marfan syndrome
      and intracranial aneurysms has been assumed. METHODS: The records of 135 patients
      classified as having Marfan syndrome who visited the Amsterdam Marfan clinic or
      were admitted to the departments of neurology and neurosurgery and the records of
      all patients with a subarachnoid hemorrhage or intracranial aneurysm who visited
      or were admitted to the departments of neurology and neurosurgery between January
      1, 1982, and January 1, 1994, were retrieved. The literature was reviewed
      regarding Marfan syndrome and intracranial aneurysms. RESULTS: No patient
      visiting the Marfan clinic had a symptomatic intracranial aneurysm. No patient
      with Marfan syndrome had been admitted with a ruptured intracranial aneurysm at
      the departments of neurology or neurosurgery in this period, while during that
      period 826 patients with symptomatic intracranial aneurysms had been admitted.
      During follow-up of 129 of the 135 patients with Marfan syndrome (2850
      retrospective patient observation years and 581 prospective patient observation
      years), none presented a symptomatic intracranial aneurysm. The suggested
      relationship between Marfan syndrome and intracranial aneurysms is based mainly
      on 10 case reports. However, the diagnosis of Marfan syndrome is doubtful in
      several of these reports. Several large studies of patients with Marfan syndrome
      did not mention a ruptured intracranial aneurysm as a clinical manifestation.
      CONCLUSIONS: We conclude that there is insufficient evidence to presume a
      relationship between symptomatic intracranial aneurysms and Marfan syndrome on
      the basis of currently available data.

PMID- 8553384
TI  - Comparative study of power-based versus mean frequency-based transcranial color
      coded duplex sonography in normal adults.
AB  - BACKGROUND AND PURPOSE: Power-based transcranial color-coded duplex sonography (p
      TCCD) is a new ultrasonic method that has advantages compared with frequency
      based TCCD (f-TCCD), since it is essentially independent of the angle of
      insonation, not subject to aliasing, and has a better signal-to-noise ratio. The
      purpose of this study was to evaluate the ability of p-TCCD to visualize flow in
      cerebral parenchyma and to compare the advantages, limitations, and reliability
      of velocity measurements of p-TCCD versus f-TCCD in the major basal cerebral
      arteries of normal subjects. METHODS: Two investigators performed 15 p-TCCD and
      15 f-TCCD studies in 30 normal subjects with adequate ultrasonic windows. Each
      investigator did a p-TCCD or f-TCCD study in every patient, and each was blinded
      in every case to the results of the other. Peak systolic (Vs) and end-diastolic
      (Vd) velocities were determined in the anterior, middle, and posterior cerebral,
      basilar, and vertebral arteries. The reliability of p-TCCD velocimetry was
      evaluated by calculating both the correlation coefficient (r) of the difference
      between p-TCCD versus f-TCCD measurements and the coefficient of variation (CV),
      defined as the difference between the mean values for p-TCCD and f-TCCD divided
      by the mean values for f-TCCD measurements, expressed as percent. RESULTS: p-TCCD
      did not display flow in cerebral parenchyma but depicted arteries with a course
      perpendicular to that of the ultrasound beam and showed good reliability of
      velocity measurements in all examined arteries: for Vs, r was .84 to .93 (P <
      .001) and CV was 7.7% to 10.8%; for Vd, r was .87 to .90 (P < .001) and CV was
      10.3% to 13.7%. The lack of directional and velocity information and tissue
      motion artifacts were unimportant limitations in p-TCCD. CONCLUSIONS: Compared
      with f-TCCD, p-TCCD had no important advantages but had several unimportant
      limitations in a study of normal adults with adequate ultrasonic windows.

PMID- 8553385
TI  - Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia
      plus blood flow promotion.
AB  - BACKGROUND AND PURPOSE: In past studies, cerebral outcome after normothermic
      cardiac arrest of 10 or 12.5 minutes in dogs was improved but not normalized by
      resuscitative (postarrest) treatment with either mild hypothermia or hypertension
      plus hemodilution. We hypothesized that a multifaceted combination treatment
      would achieve complete cerebral recovery. METHODS: With our established dog
      outcome model, normothermic ventricular fibrillation of 11 minutes (without blood
      flow) was followed by controlled reperfusion (with brief normothermic
      cardiopulmonary bypass simulating low flow and low PaO2 of external
      cardiopulmonary resuscitation) and defibrillation at < 2 minutes. Controlled
      ventilation was provided to 20 hours and intensive care to 96 hours. Control
      group 1 (n = 8) was kept normothermic (37.5 degrees C), normotensive, and
      hypocapnic throughout. Experimental group 2 (n = 8) received mild resuscitative
      hypothermia (34 degrees C) from about 10 minutes to 12 hours (by external and
      peritoneal cooling) plus cerebral blood flow promotion with induced moderate
      hypertension, mild hemodilution, and normocapnia. RESULTS: All 16 dogs in the
      protocol survived. At 96 hours, all 8 dogs in control group 1 achieved overall
      performance categories 3 (severe disability) or 4 (coma). In group 2, 6 of 8 dogs
      achieved overall performance category 1 (normal); 1 dog achieved category 2
      (moderate disability), and 1 dog achieved category 3 (P < .001). Final
      neurological deficit scores (0% [normal] to 100% [brain death]) at 96 hours were
      38 +/- 10% (22% to 45%) in group 1 versus 8 +/- 9% (0% to 27%) in group 2 (P <
      .001). Total brain histopathologic damage scores were 138 +/- 22 (110 to 176) in
      group 1 versus 43 +/- 9 (32 to 56) in group 2 (P < .001). Regional scores showed
      similar group differences. CONCLUSIONS: After normothermic cardiac arrest of 11
      minutes in dogs, resuscitative mild hypothermia plus cerebral blood flow
      promotion can achieve functional recovery with the least histological brain
      damage yet observed with the same model and comparable insults.

PMID- 8553386
TI  - Amelioration of impaired cerebral metabolism after severe acidotic ischemia by
      tirilazad posttreatment in dogs.
AB  - BACKGROUND AND PURPOSE: Acidosis may contribute to ischemic injury by mobilizing
      iron because the iron chelator deferoxamine improves early metabolic recovery
      from hyperglycermic ischemia. Mobilized iron may then promote oxygen radical
      induced lipid peroxidative injury during reperfusion. We tested the hypothesis
      that administration of the antioxidant tirilazad at the start of reperfusion
      improves early metabolic recovery after severe acidotic ischemia and ameliorates
      depletion of the endogenous antioxidant glutathione. METHODS: In anesthetized
      dogs, arterial glucose concentration was increased to 500 to 600 mg/dL and global
      incomplete cerebral ischemia was produced for 30 minutes by ventricular fluid
      infusion to reduce perfusion pressure to 10 to 12 mm Hg. Metabolic recovery and
      intracellular pH were measured by phosphorus MR spectroscopy. In the first
      experiment, four groups of eight dogs each received either vehicle or 0.25, 1, or
      2.5 mg/kg of tirilizad mesylate at reperfusion. Cerebral blood flow was measured
      with microspheres. In the second experiment, two groups of eight dogs each each
      received either vehicle or 2.5 mg/kg of tirilazad at reperfusion, and cortical
      glutathione was measured at 3 hours of reperfusion. RESULTS: Cerebral blood flow
      decreased to approximately 6 mL/min per 100 g and intracellular pH decreased to
      approximately 5.6 during ischemia in all groups. In the vehicle group, ATP
      recovery was transient and pH remained less than 6.0. Cerebral blood flow, O2
      consumption, and ATP eventually declined to near-zero levels by 3 hours. Recovery
      was improved by tirilazad posttreatment in a dose-dependent fashion. At the
      highest dose, cerebral blood flow and O2 consumption were sustained near
      preischemic levels, and five of eight dogs had recovery of ATP greater than 50%
      and of pH greater than 6.7. Recovery of ATP and phosphocreatine became
      significantly greater than that in the vehicle group by 17 minutes of reperfusion
      despite similar levels of early hyperemia, indicating that the drug was acting
      before the onset of hypoperfusion. Cortical glutathione concentration in the
      vehicle group was 27% less than that in the tirilazad group and 34% less than
      that in nonischemic controls. CONCLUSIONS: Decreased depletion of the endogenous
      antioxidant glutathione is consistent with tirilazad acting as an antioxidant in
      vivo. Improvement in high-energy phosphate recovery 17 minutes after starting
      tirilazad infusion during reperfusion is consistent with an early onset of a
      functionally significant oxygen radical injury. Thus, severe acidosis appears to
      contribute to early ischemic injury through an oxygen radical mechanism
      sufficient to impede metabolic recovery.

PMID- 8553387
TI  - Trauma-induced neurotoxicity in rat hippocampal neurons.
AB  - BACKGROUND AND PURPOSE: We have previously shown that traumatic injury of
      hippocampal cells triggers release of a soluble neurotoxin that can be
      transferred to an uninjured culture. The mechanism of this trauma-induced
      neurotoxicity is independent of glutamate receptor activation. We extended this
      observation to study the mechanism of this neurotoxicity. METHODS: Dissociated
      rat hippocampal neurons were traumatized by disrupting the culture by scratching
      the plate. The toxicity expressed by the injured culture was studied by
      transferring the medium to an uninjured culture and assessing the death rate by
      trypan blue exclusion. RESULTS: This neurotoxin is stable in the medium at room
      temperature for several hours and withstands boiling. The molecular weight is
      between 100 and 500. The release and the effect of this toxin seem to be
      independent of glutamate receptor activation. The toxicity is unaffected by
      removal of extracellular calcium. However, dantrolene dose-dependently blocked
      the toxicity in the recipient culture, suggesting that the release of
      intracellular stores of calcium is involved in the toxic effect. This release of
      calcium is likely to be followed by an activation of nitric oxide synthase
      because competitive nitric oxide synthase inhibitors attenuated this toxicity.
      Consistent with this result, cholecystokinin octapeptide significantly reduced
      cell death when combined with this toxic medium. CONCLUSIONS: Traumatic injury of
      dissociated cells can propagate neurotoxicity in uninjured cells by a soluble
      toxin released into the extracellular space. This toxin causes a rise in
      cytosolic calcium that activates nitric oxide synthase that can be blocked by
      cholecystokinin.

PMID- 8553388
TI  - Effects of cerebral ischemia on N-methyl-D-aspartate and dihydropyridine
      sensitive calcium currents. An electrophysiological study in the rat hippocampus
      in situ.
AB  - BACKGROUND AND PURPOSE: During cerebral ischemia, both promoting and limiting
      factors are present for activation of the N-methyl-D-aspartate (NMDA) receptor
      ion channel and the dihydropyridine (DHP)-sensitive Ca2+ channels. We
      investigated the activity of these channels during ischemia and reperfusion in
      the rat hippocampus in situ. METHODS: Reversible ischemia was induced by
      bilateral carotid artery ligation. NMDA and BAY K8644 were applied by
      iontophoresis or pneumatic ejection, and extracellular field potential and
      resistance changes were recorded from the CA1 region of the rat hippocampus.
      Resting membrane potentials of the CA1 neurons were also recorded. RESULTS: DC
      potential shifts produced by NMDA and BAY K8644 were reduced when ischemia
      depressed the evoked activity more than 50%. They disappeared on total failure of
      synaptic transmission and recovered during reperfusion. When the evoked activity
      was depressed less than 50%, DC shifts were greater than their preischemic
      values; however, BAY K8644-induced potentiation did not reach statistical
      significance. CA1 neurons were depolarized during ischemia. CONCLUSIONS: These
      data suggest that ischemia severe enough to cause transmission failure
      inactivates NMDA and DHP-sensitive Ca2+ currents. During less intense ischemia
      and reperfusion, NMDA and DHP-sensitive Ca2+ channels are functional, and their
      overactivation may lead to neurotoxicity.

PMID- 8553389
TI  - Relationship between the volume of craniotomies for cerebral aneurysm performed
      at New York state hospitals and in-hospital mortality.
AB  - BACKGROUND AND PURPOSE: After a craniotomy for cerebral aneurysm, postoperative
      mortality can be significant. Previous studies have shown that hospitals
      performing frequent high-risk procedures (such as coronary artery bypass) have a
      lower mortality than hospitals where these procedures are performed infrequently.
      METHODS: The Statewide Planning and Research Cooperative System of the New York
      State Department of Health reviewed all discharges in New York State from 1987
      through 1993 for the diagnoses of subarachnoid hemorrhage and/or cerebral
      aneurysm and for patients with the procedure code for craniotomy for ruptured or
      unruptured cerebral aneurysm. In-hospital mortality and length of stay were
      examined in relation to the volume of craniotomies for aneurysm performed at each
      individual hospital. RESULTS: A total of 15,376 discharges for subarachnoid
      hemorrhage and 5638 craniotomies for aneurysm were tabulated in 208 hospitals.
      For all patients who underwent craniotomy for ruptured cerebral aneurysm (n =
      4034), there was a 43% (95% confidence interval, 29% to 57%) reduction in
      mortality rate in hospitals performing more than 30 craniotomies per year for
      cerebral aneurysm compared with hospitals performing less surgery (8.8% versus
      15.5%, P < .0001). For all patients who underwent craniotomy for unruptured
      cerebral aneurysm (n = 1604), there was an identical 43% (95% confidence
      interval, 14% to 73%) reduction in mortality in hospitals performing more than 30
      craniotomies per year for cerebral aneurysm (4.6% versus 8.1%, P = .0087).
      CONCLUSIONS: Hospitals that frequently perform aneurysm operations have lower
      mortality rates for patients undergoing craniotomy for cerebral aneurysm than
      hospitals that perform fewer operations.

PMID- 8553391
TI  - Influence of the intra-aortic balloon pump on the transcranial Doppler flow
      pattern in a brain-dead patient.
AB  - BACKGROUND: Confirmation of clinical brain death with transcranial Doppler (TCD)
      has been described. With the introduction of mechanical assist devices, it is
      important to know how these devices influence TCD measurements. CASE DESCRIPTION:
      A patient who fulfilled the clinical criteria for brain death after cardiac
      arrest is described. An intra-aortic balloon pump (IABP) was necessary to
      maintain hemodynamic stability. A TCD examination was performed as an adjunct to
      the clinical diagnosis of brain death. A pattern of reversal of blood velocity
      typical of brain death was observed. With the IABP functioning, an increase of
      mean forward flow velocity without appreciable increase in the net flow
      velocities was seen. The results of the TCD measurements with the IABP
      functioning are not in concordance with values reported in the literature that
      confirm the clinical diagnosis of brain death. CONCLUSIONS: Application of TCD in
      a patient with an IABP could lead to false interpretation of results if the TCD
      mean velocities are not registered with the IABP on standby or if the net flow
      velocities are not calculated.

PMID- 8553390
TI  - Ischemia reduces CGRP-induced cerebral vascular dilation in piglets.
AB  - BACKGROUND AND PURPOSE: Effects of anoxic stress on cerebrovascular responses to
      calcitonin gene-related peptide (CGRP) have not been examined previously. We
      determined the effects of total global ischemia on cerebral arteriolar responses
      to CGRP in newborn pigs. METHODS: Piglets were anesthetized and ventilated with a
      respirator. Pial arteriolar diameter was determined using a closed cranial window
      and intravital microscopy. Baseline arteriolar diameters ranged from 80 to 100
      microns. Arteriolar responses to 10(-9) and 10(-8) mmol/L CGRP applied topically
      were determined before and 1, 2, and 4 hours after a 10-minute period of total
      global ischemia. Ischemia was caused by increasing intracranial pressure.
      RESULTS: Before ischemia, CGRP dilated arterioles by 14 +/- 2% (n = 6) and 24 +/-
      3% (n = 7) at 10(-9) and 10(-8) mmol/L, respectively. However, after ischemia,
      arteriolar responses to 10(-9) mmol/L CGRP were reduced at 1 hour to 4 +/- 1%, at
      2 hours to 3 +/- 2%, and at 4 hours to 5 +/- 4% (P < .05 for all comparisons).
      Similarly, arteriolar responses to 10(-8) mmol/L CGRP were reduced to 5 +/- 2% at
      1 hour, 5 +/- 2% at 2 hours, and 10 +/- 6% at 4 hours (P < .05 for all
      comparisons). In time control animals, arteriolar responses to CGRP did not
      change over time. In other animals, we examined effects of pretreatment with
      indomethacin (5 mg/kg IV) on ischemia-induced decreases in arteriolar responses
      to CGRP. Indomethacin administration did not preserve arteriolar dilation to CGRP
      at 1 hour after ischemia, but responses were normal at 2 hours. CONCLUSIONS:
      Total global ischemia leads to prolonged attenuated dilator responses of cerebral
      arterioles to CGRP. In addition, indomethacin treatment alters effects of
      ischemia on CGRP-induced dilation.

PMID- 8553392
TI  - Stroke in Williams syndrome.
AB  - BACKGROUND: Williams syndrome is a genetic disorder characterized by a high
      incidence of heart disease, arterial stenosis, and hypertension. Despite these
      features, cerebrovascular accidents have been described only recently and only in
      association with stenoses of the cerebral vasculature. CASE DESCRIPTION: A 19
      year-old girl with Williams syndrome developed an acute-onset hemiparesis. MRI
      demonstrated an infarct involving the internal capsule and putamen. No stenotic
      areas were seen on angiography. CONCLUSIONS: Stroke should be considered as a
      possible consequence of Williams syndrome, even in the absence of stenoses of the
      cerebral vasculature. Comparison of this case with those previously reported in
      the literature emphasizes the multiplicity of features in Williams syndrome that
      can contribute to the risk of stroke.

PMID- 8553393
TI  - Vasospasm/thrombus in cerebral ischemia related to cocaine abuse.

PMID- 8553394
TI  - Improvement following stroke.

PMID- 8553395
TI  - Susac's syndrome: improvement with combined antiplatelet and calcium antagonist
      therapy.

PMID- 8553396
TI  - Nylon monofilament for intraluminal middle cerebral artery occlusion in rats.

PMID- 8553397
TI  - Comparison of rehabilitation practice on hospital wards for stroke patients.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to observe patients on a stroke
      unit and to compare their activity with that of patients on conventional hospital
      wards to identify aspects of rehabilitation practice that might account for
      differences in outcome. METHODS: Stroke patients admitted to the hospital were
      observed on three 8-hour shifts over 3 consecutive days. An observer recorded, at
      10-minute intervals, where patients were, what they were doing, and whether their
      positioning was as recommended by rehabilitation therapists. Patients on a stroke
      unit were compared with those on conventional wards. RESULTS: Stroke unit
      patients spent less time by their beds and more time in other locations on the
      ward (P < .001). There were significant differences in the frequency of behaviors
      observed in the two types of ward (P < .001). Stroke unit patients had
      significantly more interaction with nurses and therapists (P < .001). They were
      also more often in the recommended position (P < .001). CONCLUSIONS: The
      proportion of time in therapeutic activity was low in all locations, with
      patients spending many hours sitting and doing nothing. Despite this, stroke unit
      patients had more therapeutic contact with staff and were more often in the
      recommended position. These two features may account for some of the differences
      in outcome.

PMID- 8553398
TI  - Vascular risk factors and arteriosclerotic disease in idiopathic normal-pressure
      hydrocephalus of the elderly.
AB  - BACKGROUND AND PURPOSE: There is some evidence from previous studies that
      idiopathic normal-pressure hydrocephalus (NPH) of the elderly might be linked to
      vascular leukoencephalopathy. The purpose of this study was to examine the
      prevalence and impact of vascular risk factors and vascular diseases in
      idiopathic NPH compared with a control cohort. METHODS: The prevalence of
      arterial hypertension; diabetes mellitus; hypercholesterolemia; hyperlipidemia;
      smoking; obesity; and cardiac, cerebrovascular, and other arteriosclerotic
      diseases was assessed in 65 patients with idiopathic NPH. The findings were
      compared with those of 70 patients with comparable age distribution. To describe
      the differences of the prevalences of vascular risk factors, odds ratios were
      obtained by univariate and multivariate analyses. RESULTS: The univariate
      analysis revealed significant associations between idiopathic NPH and arterial
      hypertension (prevalence, 54 of 65 [83%]; control group, 25 of 70 [36%]; P <
      .001) and diabetes mellitus (prevalence, 31 of 63 [49%]; control group, 20 of 70
      [29%]; P < .015) but not with other vascular risk factors. After multivariate
      regression analysis, only hypertension remained significantly associated with NPH
      (P < .0001). There was also a significant association between NPH and cardiac (P
      < .001), cerebral arteriosclerotic (P = .007), and other arteriosclerotic
      diseases (P = .001). A positive association was found between the severity of
      clinical symptoms of NPH and the presence of hypertension, especially for gait
      disturbance. The presence of hypertension was not related to the duration of NPH.
      CONCLUSIONS: Our data show a highly significant association between idiopathic
      NPH and arterial hypertension. Arterial hypertension might be involved in the
      pathophysiological mechanisms promoting idiopathic NPH.

PMID- 8553399
TI  - Comparison of different diagnostic criteria for vascular dementia (ADDTC, DSM-IV,
      ICD-10, NINDS-AIREN).
AB  - BACKGROUND AND PURPOSE: Vascular dementia (VD) has been an ill-defined term thus
      far. Recently detailed criteria for the diagnosis of VD have been proposed
      (Alzheimer's Disease Diagnostic and Treatment Centers [ADDTC], 1992; Diagnostic
      and Statistical Manual of Mental Disorders, 4th edition [DSM-IV], 1994;
      International Classification of Diseases, 10th revision [ICD-10], 1992, 1993; and
      National Institute of Neurological Disorders and Stroke-Association
      Internationale pour la Recherche et l'Enseignement en Neurosciences [NINDS
      AIREN], 1993). Until now the clinical feasibility of these diagnostic guidelines
      has not been evaluated. METHODS: This study aimed to compare these criteria in an
      unselected sample of 167 elderly patients (mean age, 72.0 +/- 9.9 years) admitted
      with probable dementia. RESULTS: The number of cases that could be classified as
      VD differed widely between the various diagnostic guidelines. According to DSM-IV
      criteria, 45 cases were diagnosed as VD. Twenty-one cases fulfilled the ICD-10
      research criteria, but only 12 met the NINDS-AIREN criteria for VD. Twenty-three
      cases were classified as ischemic VD as defined by the ADDTC criteria. The
      concordance was very poor since only 5 cases met the criteria for VD of all
      diagnostic guidelines. CONCLUSIONS: Our results show that the classification
      according to different diagnostic guidelines yields rather distinct groups of
      patients. The reasons responsible for these findings are as follows: (1)
      different criteria for dementia, (2) limitation to ischemic VD in the ADDTC
      criteria, (3) no further differentiation of VD into subtypes according to CT or
      MRI findings (DSM-IV), and (4) the multifactorial etiopathology of VD. Major
      diagnostic difficulties ensue from the very frequent cases with white matter
      lesions, since their etiology and classification remain widely unknown.

PMID- 8553400
TI  - Role of insulin resistance associated with compensatory hyperinsulinemia in
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Although insulin resistance and hyperinsulinemia play a
      crucial role in the pathogenesis of atherosclerosis, little is known about their
      roles in ischemic stroke. The purpose of this study was to clarify whether
      insulin resistance and hyperinsulinemia are causative factors in the pathogenesis
      of ischemic stroke. METHODS: Thirty-four consecutive patients with ischemic
      stroke, who were normotensive, nondiabetic, and not obese, were classified into
      three groups--atherothrombotic infarction (n = 16), lacunar infarction (n = 10),
      and cardioembolic infarction (n = 8)--based on clinical findings, brain imaging,
      and cerebral angiography. Both oral glucose tolerance tests and lipid analyses
      were performed. Insulin sensitivity was determined by the steady state plasma
      glucose method with the use of octreotide acetate. Data were compared with those
      of healthy control subjects (n = 15). RESULTS: Steady state plasma glucose levels
      were significantly higher in the atherothrombotic infarction group compared with
      control subjects and the other two stroke groups, indicating the presence of
      insulin resistance in patients with atherothrombotic infarction. In the
      atherothrombotic infarction group, the 2-hour insulin area (area under the plasma
      insulin concentration curve) during a 75-g oral glucose tolerance test was
      significantly increased and dyslipidemic changes (increased triglyceride and
      apolipoprotein B, decreased high-density lipoprotein) were observed, whereas
      these changes were not found in the lacunar infarction and cardioembolic stroke
      groups. CONCLUSIONS: Insulin resistance in association with compensatory
      hyperinsulinemia and dyslipidemia may be an important pathogenetic factor
      underlying the development of atherothrombotic infarction.

PMID- 8553401
TI  - Ischemic stroke in the elderly. Role of the common factor V mutation causing
      resistance to activated protein C.
AB  - BACKGROUND AND PURPOSE: A common missense mutation in coagulation factor V (Arg
      506 Gln) creates phenotypic resistance to the anticoagulant effects of activated
      protein C and predisposes carriers to venous thrombosis. To assess a correlation
      between this common hypercoagulable state and ischemic cerebrovascular disease,
      we have compared the prevalence of this mutation in a group of stroke patients
      with that in several control patient groups. METHODS: The presence of the factor
      V Arg 506 Gln mutation was determined by a direct polymerase chain reaction-based
      assay on peripheral blood leukocytes from 161 elderly patients with acute
      ischemic stroke, 116 elderly patients with stroke risk factors but without acute
      stroke, 54 healthy elderly control subjects, and 287 younger control individuals
      (197 blood donors and 90 neonates). RESULTS: The prevalence of the heterozygous
      Arg 506 Gln factor V mutation was not significantly different in the elderly
      stroke patients (2.5%) compared with either of the age-matched control groups (2%
      to 4%). The prevalence of this mutation was significantly higher in each of two
      younger control groups (approximately 8%) than in the elderly stroke patients
      (2.5%). CONCLUSIONS: The common factor V Arg 506 Gln mutation predisposing to
      venous thrombosis is not a significant genetic risk factor for ischemic stroke in
      the elderly.

PMID- 8553402
TI  - Cerebral oximetry in patients undergoing carotid endarterectomy under regional
      anesthesia.
AB  - BACKGROUND AND PURPOSE: Near-infrared spectroscopy is a technique that can
      potentially monitor changes in cerebral oxygenation. There are at present limited
      clinical data regarding the value of this technology in relating neurological
      outcome to cerebrovascular hemoglobin oxygen saturation (ScO2). This
      investigation reports changes in ScO2 due to carotid cross-clamping during
      carotid endarterectomy in awake patients. METHODS: ScO2 was monitored in 38 adult
      patients undergoing 41 carotid endarterectomies under regional anesthesia.
      Ipsilateral and contralateral hemispheres were monitored simultaneously during 36
      operations, with ipsilateral monitoring alone in the remaining 5 operations.
      RESULTS: No significant difference was detected between ipsilateral and
      contralateral ScO2 during preclamp or postclamp periods. Carotid cross-clamping
      caused a statistically significant (P < .01) decrease in the ipsilateral ScO2,
      which decreased from 71.8 +/- 6.91% to 65.8 +/- 8.2%, while the contralateral
      ScO2 remained stable at 70.5 +/- 7.5% and 70.3 +/- 7.9%. The change in
      ipsilateral ScO2 ranged from +2.6% to -28.6% of the preclamp value. The
      difference between ipsilateral and contralateral ScO2 during cross-clamping was
      statistically significant (P < .001). The duration of cross-clamping was 39 +/-
      11 minutes (range, 18 to 89 minutes). The decrease in ipsilateral ScO2 was highly
      variable from patient to patient and did not correlate with the duration of cross
      clamping. CONCLUSIONS: These results suggest that carotid artery occlusion causes
      a statistically significant but variable decrease in ScO2 in the majority of
      patients. Data in this investigation provide a range of ScO2 values that was not
      associated with a clinically detectable neurological dysfunction.

PMID- 8553403
TI  - Sex-related differences in acetazolamide-induced cerebral vasomotor reactivity.
AB  - BACKGROUND AND PURPOSE: Cerebral vasomotor reactivity can easily be assessed
      reliably by measuring vasodilatory response to acetazolamide by transcranial
      Doppler sonography. The aim of this study was to confirm the hypothesis that
      female sex is associated with an increased cerebrovascular flow reserve. METHODS:
      Blood flow velocity of the middle cerebral artery was measured by transcranial
      Doppler sonography in 36 healthy sex- and age-matched subjects. After the initial
      blood flow velocities were recorded, the subjects received 14.3 mg/kg body wt
      acetazolamide, ie, 1 g/70 kg, intravenously. The measurements were repeatedly
      performed at 5-minute intervals starting 10 minutes after injection and lasting
      for 30 minutes. The highest measured flow velocities were used for further
      analysis. RESULTS: In both groups mean blood flow velocity increased
      significantly after acetazolamide (women, from 60.2 +/- 12.5 to 89.9 +/- 14.4
      cm/s, P < .006; men, from 54.5 +/- 18.8 to 75.7 +/- 24.5 cm/s, P < .02). The
      difference in mean blood flow velocity after acetazolamide between groups of
      women and men was statistically significant (P < .02). CONCLUSIONS: Female
      subjects show an increased vasodilatory response to the acetazolamide test
      compared with men.

PMID- 8553404
TI  - Arterial blood pressure after human cardiac arrest and neurological recovery.
AB  - BACKGROUND AND PURPOSE: In animal cardiac arrest studies, outcome has been
      improved by inducing arterial hypertension early after return of spontaneous
      circulation. The aim of our study was to evaluate whether arterial blood pressure
      within the first minutes and hours after return of spontaneous circulation
      influences neurological recovery in human cardiac arrest survivors. METHODS: Of
      136 retrospectively evaluated patients after sudden cardiac death, two groups
      were defined: group 1, mean arterial blood pressure (MABP) within 5 minutes after
      return of spontaneous circulation above 100 mm Hg; group 2, MABP of 100 mm Hg or
      less. Thereafter MABP was measured every 5 minutes until 2 hours after return of
      spontaneous circulation. The groups were compared in regard to age, sex, in/out
      of hospital, witnessed/not witnessed, first electrocardiographic rhythm, time
      from cardiac arrest to beginning of life support and to return of spontaneous
      circulation, cumulative epinephrine dose administered, and best neurological
      outcome within 6 months. RESULTS: In group 1 (n = 54) good neurological recovery
      was observed in 63% and in group 2 (n = 82) in 55% (chi 2 = 0.87, P = NS). Both
      groups exhibited comparable baseline values except that time intervals from
      beginning of life support to return of spontaneous circulation were shorter in
      group 1. After we controlled for this difference with Spearman's partial rank
      correlation (rs), there was no association between MABP measured within the first
      5 minutes and outcome (rs = -.023; P = NS). Good neurological recovery was
      independently and directly related to MABP measured during 2 hours after return
      of spontaneous circulation (rs = .26; P < .01). CONCLUSIONS: In human cardiac
      arrest survivors, good functional neurological recovery was independently and
      positively associated with arterial blood pressure during the first 2 hours after
      human cardiac arrest but not with hypertensive reperfusion within the first
      minutes after return of spontaneous circulation.

PMID- 8553405
TI  - Predictors of stroke in middle-aged patients with non-insulin-dependent diabetes.
AB  - BACKGROUND AND PURPOSE: The risk of stroke is known to be markedly elevated in
      patients with non-insulin-dependent diabetes mellitus (NIDDM), but the
      information on risk factors predicting stroke events in middle-aged NIDDM
      patients is limited. Therefore, we evaluated the significance of different
      cardiovascular risk factors with respect to the incidence of stroke in middle
      aged NIDDM patients. METHODS: Levels of cardiovascular risk factors were
      determined at baseline in 1059 NIDDM patients (581 men, 478 women) and 1373
      nondiabetic control subjects (638 men, 735 women), aged from 45 to 64 years, in
      eastern and western Finland. These patients were followed up for 7 years with
      respect to stroke events. RESULTS: Altogether, 34 NIDDM patients (13 men, 21
      women) and 5 nondiabetic subjects (4 men, 1 woman) died from stroke, and 125
      NIDDM patients (61 men, 64 women) and 30 (18 men, 12 women) nondiabetic subjects
      had a fatal or nonfatal stroke. The risk of stroke in NIDDM men was about
      threefold and in NIDDM women fivefold higher than that in corresponding
      nondiabetic subjects. Previous history of stroke increased the risk of a new
      stroke event by threefold. Patients with hyperglycemia (plasma glucose > 13.4
      mmol/L) and high hemoglobin A1 (> 10.7%) had about a twofold higher risk of
      stroke than patients with better glycemic control. Low levels of high-density
      lipoprotein cholesterol (< 0.90 mmol/L), high levels of total triglyceride (>
      2.30 mmol/L), and the presence of hypertension were associated with a twofold
      increase in the risk of stroke mortality or morbidity. CONCLUSIONS: Our
      prospective population-based study gives evidence that previous history of
      stroke, hypertension, hyperglycemia, and dyslipidemia are strong predictors of
      stroke in middle-aged patients with NIDDM.

PMID- 8553406
TI  - Risk factors and segment-specific carotid arterial enlargement in the
      Atherosclerosis Risk in Communities (ARIC) cohort.
AB  - BACKGROUND AND PURPOSE: B-mode ultrasound imaging affords the opportunity to
      quantify both intimal-medial thickness (IMT) and lumen diameter of extracranial
      carotid arteries in ambulatory populations. Since the relation of IMT to lumen
      diameter may be complex, we asked whether cardiovascular disease risk factors
      (previously shown to be associated with greater arterial IMT) are related to
      smaller lumen diameters. METHODS: We used B-mode ultrasound to quantify lumen
      diameter, interadventitial diameter, and IMT of the extracranial carotid arteries
      and assessed the relationship of these measures to body mass index, smoking, low
      density lipoprotein (LDL) and high-density lipoprotein cholesterol, hypertension,
      and diabetes in 6088 male and 7493 female participants in the Atherosclerosis
      Risk in Communities (ARIC) cohort. RESULTS: Smoking, hypertension, and LDL
      cholesterol were consistently related to greater IMT in the common and internal
      carotid arteries of men and women, as has been previously reported. In the
      internal carotid artery, smoking, hypertension, and LDL cholesterol were
      consistently related to smaller lumens. In the common carotid artery, body mass
      index, smoking, and hypertension were related to significantly larger, and LDL
      cholesterol to smaller, lumens. Thus, only LDL cholesterol was consistently
      associated with smaller lumens in both the common and internal carotid arteries.
      CONCLUSIONS: Risk factors relate positively to IMT in both the common and
      internal carotid arteries and inversely with lumen diameter in the internal
      carotid artery, in parallel with their relation to clinical events. However,
      their association with lumen diameters of the common carotid artery in population
      based samples is more complex, and in some cases adverse levels of risk factors
      may be associated with larger lumens.

PMID- 8553407
TI  - Hypertension, stroke, and coronary heart disease in relatives of patients with
      subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: First-degree relatives of patients with subarachnoid
      hemorrhage (SAH) have a three to seven times greater risk of SAH than second
      degree relatives and than the general population. If hypertension, which is in
      part genetically determined, contributes to this increased risk, the frequency of
      hypertension and its sequelae would be expected to be higher in first- than in
      second-degree relatives of patients with SAH. METHODS: We compared the reported
      frequency of hypertension, stroke, and coronary heart disease between 1290 first-
      and 3588 second-degree relatives of a prospective series of patients with SAH.
      RESULTS: The relative risk adjusted for age and survival status in first-degree
      relatives was 2.3 (95% confidence interval [CI], 1.9 to 2.9) for hypertension,
      1.8 (95% CI, 1.3 to 2.4) for stroke, and 1.9 (95% CI, 1.5 to 2.3) for coronary
      heart disease. CONCLUSIONS: Hypertension is a familial factor contributing to the
      risk of SAH. Hypertension should be sought and treated in first-degree relatives
      of patients with SAH to reduce the increased risk of cerebrovascular and
      cardiovascular diseases.

PMID- 8553408
TI  - Lubeluzole in acute ischemic stroke. A double-blind, placebo-controlled phase II
      trial. Lubeluzole International Study Group.
AB  - BACKGROUND AND PURPOSE: We aimed to assess the safety and efficacy of lubeluzole
      in patients with a clinical diagnosis of acute (< 6 hours) ischemic stroke in the
      carotid artery territory. METHODS: A randomized, double-blind, placebo-controlled
      multicenter trial was conducted in 232 patients. Because treatment was
      administered within 6 hours and a CT scan was not mandatory before the start of
      treatment, 39 patients with either an intracerebral hemorrhage or ischemic stroke
      in the vertebrobasilar circulation were excluded from the primary efficacy
      analysis as prespecified in the protocol. Of the 193 patients with acute ischemic
      stroke in the carotid artery territory (target population), 61 received placebo,
      66 lubeluzole 7.5 mg over 1 hour followed by 10 mg/d for 5 days, and 66
      lubeluzole 15 mg over 1 hour followed by 20 mg/d for 5 days. RESULTS: The trial,
      initially aimed at a patient inclusion of 270, was terminated prematurely
      according to the advice of the Safety Committee because of an imbalance in
      mortality between the treatment groups. Mortality rates at the final follow-up of
      28 days for placebo, lubeluzole 10 mg/d, and lubeluzole 20 mg/d were,
      respectively, 18%, 6%, and 35% in the target population, results that were
      confirmed in the intent-to-treat population. Multivariate logistic regression
      analysis showed that the lower mortality in the lubeluzole 10 mg/d group was
      significantly in favor of the 10 mg/d treatment (P = .019). The higher mortality
      rate in the 20 mg/d group could be explained, at least in part, by an imbalance
      at randomization that led to a higher number of patients in that group with
      severe ischemic stroke. A total of 26 of 66 patients (39%) who received
      lubeluzole 10 mg/d had a score on the Barthel Index of > 70 at day 28, indicating
      no or mild disability, compared with 21 of 61 (34%) in the placebo group and 19
      of 66 (29%) in the lubeluzole 20 mg/d group (P = NS). CONCLUSIONS: In patients
      with acute ischemic stroke, the dosage regimen of 7.5 mg over 1 hour followed by
      10 mg/d of intravenous lubeluzole is safe and statistically significantly reduced
      mortality. Further clinical trials in a larger number of patients are ongoing to
      confirm efficacy.

PMID- 8553409
TI  - Single-photon emission computed tomography using hexamethylpropyleneamine oxime
      in the prognosis of acute cerebral infarction.
AB  - BACKGROUND AND PURPOSE: The role of single-photon emission CT (SPECT) in the
      prognosis of cerebral infarction is controversial, but most studies report that
      SPECT using a variety of radiopharmaceutical agents gives useful prognostic
      information. Only one study has questioned whether acute perfusion deficits
      independently add to a valid clinical prognostic score. This study was limited to
      middle cerebral artery territory infarcts and was negative. We present data on
      the prognostic utility of SPECT using 99mTc-hexamethylpropyleneamine oxime
      (HMPAO) in cerebral infarction, unselected by site. METHODS: Fifty consecutive
      unselected patients admitted to the hospital with acute cerebral infarction, of
      whom 10 died and 7 withdrew, had SPECT performed serially at onset and at 1 week
      and 3 months after stroke onset using 99mTc-HMPAO and the NOVO 810 dedicated high
      resolution head tomograph. Clinical severity at presentation and outcome was
      measured with the Canadian Neurological Scale and the Barthel Index. Infarct
      volumes were measured from both the SPECT and CT scans. The data for the 43
      subjects who completed the study or died were evaluated to determine the most
      powerful prognostic measures. Predictors were the Canadian Neurological Scale
      score at onset and 1 week, the Barthel Index at 1 week, the CT infarct volume
      typically done between 3 and 7 days after stroke onset, and the infarct volumes
      at the first and second SPECT. Outcome measures were the Canadian Neurological
      Scale score and Barthel Index score at 3 months, scored as zero for those
      patients who died. RESULTS: The clinical prognostic indicators correlated with
      the outcome measures, with coefficients between .617 and .821 (P < .0006 in all
      cases). The Canadian Neurological Scale score measured at 1 week was the best of
      these. Infarct volumes measured from SPECT correlated less well (coefficients
      between -.518 and -.683, P < .0019 in all cases). CT infarct volume was the
      poorest predictor. Although SPECT infarct volumes predicted outcome, they did so
      less well than clinical examination. Spontaneous infarct reperfusion did not
      affect outcome. CONCLUSIONS: Although the measurement of infarct volume on SPECT
      using 99mTc-HMPAO provides a predictor of stroke outcome, it is not a better
      predictor than the Canadian Neurological Scale score.

PMID- 8553410
TI  - Comparison of transcranial Doppler ultrasonography and transesophageal
      echocardiography to monitor emboli during coronary artery bypass surgery.
AB  - BACKGROUND AND PURPOSE: Transcranial Doppler ultrasonography (TCD) is the
      standard technique for monitoring emboli in the cerebral circulation. Embolic
      signals have been detected with the use of this technique in most patients
      undergoing coronary artery bypass surgery. We previously reported that the
      majority of emboli are detected after release of aortic cross-clamps and partial
      occlusion clamps. In this study we compare the intraoperative use of TCD with
      transesophageal echocardiography (TEE) to monitor cerebral emboli. METHODS: We
      simultaneously monitored 20 patients undergoing coronary bypass surgery with TCD
      and TEE. All patients also underwent routine TEE examination of the aorta.
      RESULTS: Embolic signals were detected in all patients by both techniques. Mean
      total number of emboli was 535 +/- 109 by TEE compared with 133 +/- 28 by TCD. We
      found correlation between numbers of emboli detected by the two techniques at
      clamp placement and release (r = .65, P = .002). Clamp placement and release
      accounted for 84% of all emboli by TEE and 83% by TCD. By TEE, large, highly
      echogenic particles were detected after clamp release compared with small, barely
      echodense particles at the onset of bypass. No such distinction was apparent by
      TCD. We found correlation between severity of aortic atheroma and both TEE- (P =
      .003) and TCD-detected (P = .009) emboli. CONCLUSIONS: TEE and TCD can both be
      used to continuously monitor emboli during coronary artery bypass surgery.
      However, TEE is invasive and justified only if it is being performed for
      intraoperative assessment of aortic atheromatosis or cardiac function.

PMID- 8553411
TI  - Sonographic assessment of carotid artery stenosis. Comparison of power Doppler
      imaging and color Doppler flow imaging.
AB  - BACKGROUND AND PURPOSE: Power Doppler imaging (PDI) is a new ultrasound technique
      that, in contrast to color Doppler flow imaging (CDFI), generates intravascular
      color signals from the reflected echo amplitude depending mainly on the density
      of red blood cells. We evaluated the diagnostic significance of PDI compared with
      CDFI for the measurement of carotid stenosis and characterization of plaque
      surface. METHODS: In 25 internal carotid artery stenoses, reduction of the
      intrastenotic lumen contrasted by blood density signals and color Doppler signals
      on longitudinal and transverse views was assessed for correlative evaluation. In
      addition, the peak systolic flow velocity of the Doppler spectrum was correlated
      with PDI and CDFI measurements. RESULTS: PDI provided good visualization of the
      residual lumen in all stenoses, whereas displays on CDFI were inadequate in two
      calcified plaques. PDI revealed two ulcerative stenoses classified as smooth on
      CDFI. The correlation between PDI and CDFI was high for measurement of area
      stenosis (r = .93) and moderate for diameter stenosis (r = .73). Similarly, cross
      sectional reduction on both imaging methods correlated more significantly with
      peak systolic flow velocity than diameter reduction. CONCLUSIONS: This pilot
      study suggests that PDI provides additional information for luminal measurement
      and characterization of plaque surface in complicated high-grade carotid
      stenosis. Because of the absent visualization of hemodynamics, PDI should be used
      in combination with CDFI.

PMID- 8553412
TI  - Cerebrovascular disease assessed by color-flow and power Doppler ultrasonography.
      Comparison with digital subtraction angiography in internal carotid artery
      stenosis.
AB  - BACKGROUND AND PURPOSE: An understanding of carotid atherosclerosis is important
      to further our knowledge regarding the etiology of cerebral ischemia, and
      therefore it is necessary to accurately visualize carotid stenosis. The purpose
      of the present study was to compare different imaging techniques to determine
      their advantages and disadvantages in the diagnosis and quantification of middle-
      and high-grade internal carotid artery stenosis. In particular, we were
      interested in evaluating the effectiveness of the new ultrasound technique power
      Doppler. METHODS: Fifty-four patients with greater than 50% extracranial internal
      carotid artery stenosis, as determined by continuous-wave Doppler, were recruited
      prospectively to serve as subjects. All subjects were examined with color-flow
      Doppler, power Doppler, and digital subtraction angiography to enable
      visualization of carotid stenosis and plaque surface morphology. RESULTS: Thirty
      four middle-grade stenoses (50% to 69%), 32 high-grade stenoses (70% to 99%), and
      7 complete occlusions of the internal carotid artery were diagnosed with the use
      of digital subtraction angiography. Power Doppler visualized stenosis
      significantly more frequently and accurately than color-flow Doppler. Color-flow
      Doppler tended to overestimate and underestimate in patients with both middle-
      and high-grade stenosis. Power Doppler was superior to both color-flow Doppler
      and angiography with regard to differentiation of plaque surface morphology.
      CONCLUSIONS: This study demonstrates that power Doppler is an important,
      noninvasive imaging technique that has several advantages over color-flow Doppler
      in diagnosing carotid artery stenosis and visualizing plaque surface. Power
      Doppler, used in concert with other ultrasound techniques, should enable a more
      accurate detection and treatment of cerebrovascular disease.

PMID- 8553413
TI  - A prospective study of adolescent suicidal behavior following hospitalization.
AB  - Identification of factors associated with adolescent suicidal behavior following
      psychiatric hospitalization would facilitate development of effective aftercare
      interventions. This prospective study identified specific predictors of suicidal
      behavior in 100 adolescents during a 6-month follow-up period. Standardized
      baseline assessments and structured follow-up telephone interviews were conducted
      with adolescents and their guardians. Eighteen percent of adolescents reported
      suicidal behavior during the follow-up period, primarily of low medical lethality
      and minimal or ambivalent suicidal intent. This behavior was associated with
      suicidal thoughts, family dysfunction, and dysthymia. It was not associated with
      initial posthospitalization treatment compliance. Implications of these findings
      are discussed.

PMID- 8553414
TI  - Psychosocial correlates of suicidal ideation in adolescent psychiatric
      inpatients.
AB  - The Beck Scale for Suicide Ideation (BSI) was administered to 121 inpatients
      between 12 and 17 years old who were diagnosed with mixed psychiatric disorders.
      Twelve background and clinical characteristics, previously found to be associated
      with adolescent suicidal ideation, were entered into a multiple regression to
      estimate the BSI scores, along with the Beck Anxiety Inventory, the revised Beck
      Depression Inventory (BDI), the Beck Hopelessness Scale (BHS), and the Youth Self
      Report. The BHS and the BDI were the only two variables that contributed unique
      variance to the explanation of the BSI scores.

PMID- 8553415
TI  - Reasons for living among Chinese adolescents in Hong Kong.
AB  - Two hundred and seventy-nine secondary school students in Hong Kong responded to
      the Chinese version of the Reasons for Living Inventory. The importance of these
      reasons could be adequately described by five dimensions interpreted as Positive
      Values and Self-Efficacy, Optimism, Family Concerns, Concerns for Social
      Disapproval, and Suicidal Fears. These dimensions corresponded closely to the
      original subscales of the inventory. Implications of the importance of gender and
      age group differences in endorsing coping beliefs, rather than fears, in time of
      crisis are discussed.

PMID- 8553416
TI  - Psychosocial correlates of suicide attempts among junior and senior high school
      youth.
AB  - Three groups of junior and senior high schools students (total N = 1050)
      recruited in rural counties of a mid-Atlantic state--those who had made a prior
      suicide attempt, those reporting high levels of depressed mood or suicidal
      ideation, and those who were not depressed or suicidal--were compared with regard
      to their reports of a number of potential risk factors for suicidal behavior.
      Adolescents with a history of a suicide attempt reported more frequent stresses
      related to parents, lack of adult supports outside of the home, police, and
      sexuality (i.e., concerns about pregnancy, pressure to have sex, getting sexually
      transmitted diseases), compared with both depressed/suicide ideators and
      nondepressed adolescents. Suicide attempters were also more likely than the other
      adolescents to report that they were physically hurt by a parent, that they ran
      away from home, that they lived apart from both parents, and that they knew
      someone who had completed suicide. Results are discussed in the context of prior
      studies of adolescent suicidal behavior in community and clinical samples.

PMID- 8553417
TI  - Dimensions of suicide: perceptions of lethality, time, and agony.
AB  - Two hundred ninety-one lay persons and 10 forensic pathologists rated the
      lethality, time, and agony for 28 methods of suicide for 4117 cases of completed
      suicide in Los Angeles County in the period 1988-1991. Whereas pathologists
      provided consistent ratings, lay persons demonstrated extreme variability and a
      tendency to inflate ratings of all three dimensions. Significant gender
      differences emerged, with females rating frequently used suicide methods more
      similarly to pathologists than the males did. Males who suicided used the most
      lethal and quickest methods whereas females selected methods varying in
      lethality, duration, and agony. African Americans were overrepresented in the use
      of the most lethal and quickest methods.

PMID- 8553418
TI  - A method for reporting self-harm according to level of injury and location on the
      body.
AB  - Self-mutilation occurs on a continuum from superficial to severe, yet previous
      studies have not differentiated these acts. This study, conducted over 4 years
      with emotionally disturbed adolescents, presents a method for reporting four
      levels of severity of self-mutilation. A group of 32 subjects inflicted 128 self
      mutilations. Each wound was rated for level of injury and was mapped according to
      the location of the wound on the body. This method for reporting self-mutilation
      was seen as an efficient and reliable procedure for describing the full continuum
      of self-inflicted injuries. The term self-harm was seen as a more accurate and
      useful description of these behaviors.

PMID- 8553419
TI  - Psychological intervention, spontaneous remission, hopelessness, and psychiatric
      disturbance in adolescent parasuicides.
AB  - A study of 40 Indian adolescent parasuicides in South Africa showed that these
      subjects have significantly higher levels of hopelessness and psychiatric
      disturbance than nonsuicidal controls. Approximately half the parasuicides
      received psychological intervention. Posttesting at 6 months revealed that the
      treated subjects improved significantly on measures of hopelessness and
      psychiatric disturbance. The untreated subjects showed no significant reduction
      in hopelessness although they improved significantly on ratings of psychiatric
      disturbance. The results are discussed with possible explanations and
      recommendations.

PMID- 8553420
TI  - Serum lipids in suicide attempters.
AB  - As other studies have shown possible associations of low serum cholesterol
      concentrations as well as serotonin and corticosteroid deviances with suicide or
      depression, the present study was undertaken to investigate the serum lipid
      levels in subgroups of suicide attempters. Serum lipids were determined in 72
      suicide attempters. Cerebrospinal fluid monoamine metabolites and plasma cortisol
      levels were measured, and dexamethasone suppression tests were performed.
      Hopelessness and suicidality were rated by the Hopelessness Scale (HS) and the
      Suicidal Intent Scales (SIS). The mean total serum cholesterol (TSC) level was
      5.0 +/- 1.2 mmol/L. We found no significant correlations between TSC and the
      monoamine metabolites. High-density lipoprotein cholesterol showed positive
      correlations with the dopamine metabolite homovanillic acid (r = 0.39, p = 0.04)
      and the serotonin metabolite 5-hydroxyindoleacetic acid (r = 0.34, p = 0.07). The
      SIS and HS scales did not correlate significantly with serum lipids. "Violent"
      attempters showed somewhat higher serum lipid levels than "nonviolent"
      attempters. We found no significant differences in serum lipid levels between the
      diagnostic subgroups. Hence, we could not find much support for the hypothesis of
      associations between low cholesterol levels and decreased serotonin activity in
      the brain. However, this field merits further investigation.

PMID- 8553421
TI  - Regional analyses of alcohol and suicide in Norway: some empirical
      considerations.
AB  - The association between alcohol consumption and suicide was analyzed on aggregate
      level data from Norway, applying regional units in the analyses. Thereby two
      purposes could be served: to validate previous estimates derived from time series
      analyses, and to assess an empirical indication of alcohol and suicide as
      alternative solutions. The effect of alcohol consumption on suicide rates tended
      to be higher for women than for men, which is contrary to results from time
      series analyses and what might generally be expected. The results are discussed
      with reference to causal mechanisms and alcohol and suicide as alternative
      choices of action, and methodological considerations are outlined.

PMID- 8553422
TI  - Clinicians' attitudes toward no-suicide agreements.
AB  - Though no-suicide agreements are widely used and often recommended for suicidal
      patients, their sparse empirical support leads to questions regarding their use
      with patients of various ages. To answer this question, 46 licensed psychologist
      members of a Southern state psychology association answered questions regarding
      their beliefs and attitudes about no-suicide agreements. Such agreements were
      considered more appropriate for adults or adolescents than children. They were
      judged highly appropriate with moderately suicidal patients and were expected to
      help patients postpone suicide until after a crisis had past and to help reduce
      clinicians' anxiety.

PMID- 8553423
TI  - Diffusion of responsibility in the care of a difficult patient.

PMID- 8553424
TI  - Introduction to supplemental issue: research issues in suicide and sexual
      orientation.

PMID- 8553425
TI  - Models of development: understanding risk in adolescence.
AB  - In this paper, we review developmental models for understanding adolescence as
      they might be applied to emerging sexuality and the challenges and risks that may
      be associated with different sexual orientations and identities. Models have been
      identified as: cumulative events or simultaneous change, accentuation, or
      trajectory models. Inclusion of risk and protective factors and considering the
      extent of balance between these elements of an adolescent's life is also
      discussed in terms of predicting mental health outcomes. These models have been
      particularly useful in the study of the development of psychopathology and
      clearly relate to the broader issue of understanding suicide risk during
      adolescence.

PMID- 8553426
TI  - Sexual orientation and developmental challenges experienced by gay and lesbian
      youths.
AB  - Youths with a homosexual orientation face different developmental challenges
      during adolescence than those faced by heterosexual youths or individuals who
      recognize their homosexual orientation later in life. We discuss the impact of
      "coming out," or defining a homosexual orientation, on the development and
      identity formation of youths who come out during adolescence. The process of
      coming out is presented as entailing four broad dimensions: recognizing oneself
      as lesbian or gay; exploring one's sexual orientation through the gay and lesbian
      community; disclosing one's sexual orientation to others; and becoming more
      comfortable with one's sexual orientation. Some of the major challenges faced by
      these youths are described, and future directions for research efforts are
      discussed.

PMID- 8553427
TI  - Adolescent development and the emergence of sexuality.
AB  - Adolescence is a time of significant opportunity and significant challenge.
      Challenges can be difficult for some adolescents, which may result in problems
      that are expressed as affective disturbances or by the adolescent's participation
      in risk-taking behaviors. This review emphasizes the changes in biopsychosocial
      development during adolescence. We specifically address aspects of individual
      change during the adolescent decade (e.g., biological, cognitive, psychosocial,
      and sexual development) as well as the effects of context on normal development
      and responses to challenges during this period. Predispositions or
      vulnerabilities present prior to a developmental transition may be exacerbated by
      the transition. Adolescents can become healthy adults with the encouragement to
      develop gradually by limiting the simultaneous changes they experience, where
      possible, and by supporting healthy development through developmentally
      appropriate activities and supportive relationships with adults and peers.

PMID- 8553428
TI  - Definition and measurement of sexual orientation.
AB  - Measurement and definition of sexual orientations have increasingly become a
      central focus in both research design and public policy debates. This paper
      reviews major methods, and their theoretical underpinnings, for the definition
      and measurement of sexual orientation, highlighting their limitations and
      pitfalls, both practical and conceptual. The increasing politicization of this
      area is discussed and cautioned against. Recommendations, both general and geared
      toward measurement concerns with adolescent populations, are made. A specific
      measurement strategy, which can be utilized at a number of different levels, is
      detailed.

PMID- 8553429
TI  - Risk factors for adolescent suicide and suicidal behavior: mental and substance
      abuse disorders, family environmental factors, and life stress.
AB  - This review focuses on psychopathologic risk factors for adolescent suicide and
      suicidal behavior, namely, affective, disruptive, substance abuse, psychotic, and
      personality disorders. The interaction of psychopathology with age and gender is
      discussed. The role of family environmental risk factors and stress events in
      suicide and suicidal behavior, both alone, and in interaction with
      psychopathology are reviewed. Research reviewed will include psychological;
      autopsy studies, longitudinal studies examining predictors of suicide, and
      epidemiologic studies of suicide attempts.

PMID- 8553430
TI  - Sexual orientation in adolescents who commit suicide.
AB  - It has been suggested that there is a strong relationship between suicidal
      behavior and homosexuality in adolescence. It has been further suggested that it
      is due to the stigmatization and feelings of isolation that are experienced by
      many gay adolescents. Much of the literature that has given support to these
      hypotheses has been conducted on uncontrolled nonrepresentative samples and its
      generalizability is open to question. An opportunity to examine the relationship
      in an unselected sample arose in a case control, psychological autopsy study of
      120 of 170 consecutive suicides under age 20 and 147 community age, sex, and
      ethnic matched controls living in the Greater New York City area. Homosexuality
      was defined as having had homosexual experiences or having declared a homosexual
      orientation. Three teenagers and no controls met these criteria. The difference
      was not significant. The circumstances of death were examined and are described.
      In no instance did suicide directly follow an episode of stigmatization. All
      three suicides had evidence of significant psychiatric disorder before death. In
      spite of opportunities for biased reporting, it is concluded that this study
      finds no evidence that suicide is a common characteristic of gay youth, or that
      when suicide does occur among gay teenagers, that it is a direct consequence of
      stigmatization or lack of support.

PMID- 8553431
TI  - Suicide and sexual orientation: a critical summary of recent research and
      directions for future research.
AB  - Research on the hypothesized relationship between sexual orientation and suicide
      is limited both in quantity and quality. National or statewide data on the
      frequency and causes of completed suicide in gay and lesbian people in the
      general population, including youth, do not exist. Similarly, national or
      statewide data on the frequency of suicide attempts among the general population
      or among gay and lesbian people, including youth, do not exist. Methodological
      limitations in the small research literature include a lack of consensus on
      definitions for key terms such as suicide attempt and sexual orientation,
      uncertain reliability and validity of measures for these terms, nonrepresentative
      samples, and a lack of appropriate nongay and/or nonclinical control groups for
      making accurate comparisons. These numerous methodological limitations prevent
      accurate conclusions about the role sexual orientation might play in suicidal
      behavior; the limitations also suggest opportunities for future research.
      Furthermore, recent evaluations of some school suicide-awareness programs suggest
      that these programs are ineffective and may actually have unintended negative
      effects. The premature dissemination of unproven programs is unwarranted.

PMID- 8553432
TI  - Recommendations for a research agenda in suicide and sexual orientation. Working
      Groups, Workshop on Suicide and Sexual Orientation.

PMID- 8553433
TI  - [Non-therapeutic medical experiments using mentally incompetent persons are
      legally not permissible, but what now?].

PMID- 8553434
TI  - [Quality of work and absenteeism: lower or higher in elderly workers?].
AB  - Data of the Quality of Life Surveys 1990-1993 (n = 9969) were used to examine if
      and to what extent elderly workers differ from younger workers with regard to
      perceptions of the quality of work, especially the workload, and to the
      percentage absence due to sickness. Adjusted for occupational level, educational
      level and sex, persons aged 60-64 were characterised by either a substantially
      lower or a similarly perceived workload as compared to those aged 55-59.
      Subsequently, adjusted for the occupational level, educational level, sex and
      perceived workload, a substantial lower rate of absenteeism was found for persons
      aged 60-64. To a certain extent comparable results were found in the comparison
      of persons aged 55-59 with those aged 45-54. Based on the low grade of job
      participation of the elderly, it is proposed that these favourable figures
      support the notion of an age-related healthy-worker selection in the Netherlands.

PMID- 8553435
TI  - [Application of the Behavioral Observation Scale Geriatrics in residents of
      nursing homes in Flanders].
AB  - The Dutch Behaviour Observation Scale-Geriatrics (GOS-G) is designed to give a
      detailed description of the functioning of geriatric patients. This article
      reports the psychometric properties of the GOS-G for use in homes for the
      elderly. Analysed were data on 71 residents of 11 homes (they participated in a
      study on withdrawal of benzodiazepines). They were free of serious physical and
      psychological complaints. For 55 persons from 10 different homes the observation
      scale was filled out by two different care takers at three different occasions:
      twice at the start of the study with a time interval of one to three weeks, and
      once more after eight months. Sixteen residents from another rest home were
      evaluated with the GOS-G by two different care takers at one occasion. The
      findings in this selective sample suggest the total scale to be a reliable and
      valid measure of the daily functioning in homes for the elderly. Moreover, the
      total scale appears sensitive to change. The scores on the subscales 'psychotic
      behaviour' and 'disoriented behaviour' were unreliable. Observation of a more
      heterogeneous and larger sample is needed to confirm the usefulness of the GOS-G
      in homes for the elderly.

PMID- 8553436
TI  - [The treatment of chronic atrial fibrillation].
AB  - Atrial fibrillation is a common arrhythmia. It is associated with increased
      morbidity and mortality, in part secondary to an increased rate of
      thromboembolism. Considering the arrhythmia's duration, a chronic and paroxysmal
      type can be recognized. Only the former will be discussed here. Treatment of
      atrial fibrillation should be aimed at restoring sinus rhythm. This may improve
      exercise tolerance and alleviate symptoms. In addition, it may obviate the need
      for antithrombotic therapy. Electrical cardioversion is the method of choice to
      restore sinus rhythm in patients with chronic atrial fibrillation. To prevent
      arrhythmia relapses, anti-arrhythmic drugs are often prescribed. These drugs,
      however, may have serious side effects, e.g. proarrhythmia. The pros and cons of
      antiarrhythmics should therefore be considered seriously before prescribing these
      drugs. An alternative strategy is to optimize ventricular rate response (usually
      pharmacologically) while the patient maintains in atrial fibrillation. To prevent
      thromboembolism, however, the use of antithrombotic is strongly recommended in
      most of these patients.

PMID- 8553437
TI  - [Light therapy can restore a disturbed sleep/wake rhythm in dementia: but what is
      the basis of its efficacy?].
AB  - In dementia short nocturnal sleep length, agitation and naps in the day-time
      suggest a chronobiological disturbance. Bright light therapy seems indicated
      because of its chronobiological activity. However, dementia is accompanied by a
      decrease in volume and number of active cells of the suprachiasmatical nuclei,
      the internal clock. Is the circadian system still functioning then or is it
      irrevocably damaged? The findings concerning the circadian rhythm of several
      physiological functions are not consistent but do not show a weakened rhythm.
      Rest/activity and sleep/wake rhythms, however, are weaker in demented elderly
      than in their peers. All things considered the internal clock is still
      functioning and the Zeitgeber maintain their chronobiological activity. Research
      shows that bright light therapy can restore the sleep/wake rhythm in dementia but
      research does not uncover the working mechanism. Further studies can give clues
      for alternative treatments. If the effect of light therapy is based on its
      Zeitgeber function, other Zeitgeber may be considered as treatments. There is
      some evidence that an increase in social contacts is effective. The efficiency of
      light therapy can also be caused by stimulation in a situation of sensory
      deprivation. There are only anecdotical indications that this stimulus role can
      also be fulfilled by music.

PMID- 8553438
TI  - Women's health in a changing world. A continuous challenge.
AB  - There is reason to pay extra attention to women's health. Not only do
      complications related to reproduction pose risks to women's health;
      environmental, in particular cultural factors do so as well. The combination of
      sexual and economic subordination of women in many societies leads to
      discrimination which has a detrimental effect on the health of women, starting at
      birth. Violence against women has only recently been recognized as a worldwide
      problem. Over the past 20 years research and action at all levels have
      contributed to a better understanding of these problems, and more appropriate
      identification of interventions to tackle them.

PMID- 8553439
TI  - Pseudomonas aeruginosa bacteraemia in Enugu, Nigeria. A review of 24 cases.
AB  - A 4-year study of Pseudomonas aeruginosa bacteraemia was carried out at the
      University of Nigeria Teaching Hospital (UNTH) in Enugu, Nigeria. The average age
      of the patients was 14.7 years. Thirty-three per cent of the patients were
      between 0-6 months of age, with males being in the majority. Underlying
      factors/diseases were present in 70.8% of patients, with prematurity, chronic
      suppurative otitis media and leukaemia being the major ones in infancy and
      childhood and diabetes mellitus, urogenital disorders and head injuries in
      adults. Overall mortality was 50% and highest (16.6%) in the 0-6 months age
      group. Antipseudomonas antibiotics are extremely costly and therefore beyond the
      financial scope of many people in the developing world. In Nigeria
      aminoglycosides are the best affordable antibiotics.

PMID- 8553440
TI  - Measles vaccine effectiveness under field conditions. A case control study in
      Tabora region, Tanzania.
AB  - A case-control study was carried out among 225 cases and 450 controls aged below
      60 months between July and September 1991, with the aim of determining measles
      vaccine effectiveness (VE) under field conditions in Tabora region, Tanzania. VE
      was found to be 84% (95% confidence interval (CI) 61-93%) among children
      vaccinated between 9 and 59 months, and 73% (95% CI: 11-92%) in children
      vaccinated at the age of 6 to 8 months. Loosening the diagnostic criteria and/or
      establishing vaccination status from vaccine registers rather than Road to Health
      cards, lowered vaccine effectiveness results. The protective effectivity among
      children vaccinated from 6 months and above and those vaccinated from 9 months
      and above, was 79% (95% CI: 55-90%) and 84% (95% CI: 61-93%) respectively. A
      relatively higher VE was found in children vaccinated at rural health centres and
      hospitals, 89% (95% CI: 56-97%) compared with dispensaries, 70% (95% CI: 22-88%).
      It is high time for the current age at vaccination to be reviewed in the country.
      It should be noted, however, that the present observations and conclusions are
      based on a study of limited numbers of persons. Repetition at a large scale would
      seem indicated.

PMID- 8553441
TI  - Tropical pyomyositis in Gondar, Ethiopia.
AB  - Seventy-two cases of pyomyositis are reported from the north-western highlands of
      Ethiopia. The majority (76.4%) came from highland areas over 1,800 meters above
      sea level. The clinical picture of the disease was similar to that seen in other
      East African countries. Staphylococcus aureus was recovered from 69 of 72 pus
      cultures. Spontaneous rupture of abscesses was seen in two cases. Four of the
      five deaths were assumed to be due to complications of the pyomyositis. Further
      search into non-altitudinal factors is implicated to get a better insight into
      the nature of the disorder.

PMID- 8553442
TI  - Primary testicular causes of infertility. Do environmental and socio-cultural
      factors have a role?
AB  - A review of 81 cases of testicular biopsies, done as part of the routine
      investigation for oligospermia or azoospermia amongst otherwise healthy Saudi
      males, was carried out at the King Khalid National Guard Hospital, Jeddah. The
      results showed that 42% of cases had normal seminiferous tubules with adequate
      spermatogenesis. When compared with similar series from the literature, the Saudi
      population had a higher rate, 27.2%, of Sertoli-cell-only syndrome, compared to a
      range of 7.9-15% from other series. Hypospermatogenesis, maturation arrest and
      diffuse tubular atrophy with interstitial fibrosis made up 3.7, 8.6 and 16.0%
      respectively. The significance of environmental factors, socio-cultural habits
      and consanguineous marriages as possible influencing factors are highlighted.

PMID- 8553443
TI  - Output of major surgery in developing countries. Towards a quantitative
      evaluation and planning tool.
AB  - As part of a study of surgical operations in a rural African district, different
      quantitative output rates were explored. The aim was to develop methods
      facilitating major surgery output comparison between different hospitals or
      districts and between different points in time at any given hospital or district.
      All major surgical operations performed at hospitals in a Kenyan district during
      12 months in 1990-1991 were listed on record forms including age, sex, and home
      address of patients, and type of operation. Totally 3,415 major operations were
      recorded. We discuss, from a health planning perspective, four possible methods
      of quantifying the major surgery output: a) the annual number of major operations
      per 100 hospital beds; b) the number per 1,000 in-patient admissions; c) the
      number per 10,000 new out-patient consultations; and d) the number per 100,000
      catchment area population. The mean number per 100 beds was 310 (range 452-140);
      the mean number per 1,000 admissions was 69 (range 88-31), the number per 10,000
      new out-patient visits was 90 (range 182-55), and the mean number per 100,000
      catchment area population was 263 for the entire district with a range from 383
      to 119 among the five hospitals. We conclude that option a) and b) are useful and
      implementable, c) is less useful but implementable, and option d) is potentially
      very useful but not easily implementable until a catchment area population
      definition is agreed and applied.

PMID- 8553444
TI  - Cultural bowel patterns and sex difference in sigmoid volvulus morbidity in an
      Ethiopian hospital.
AB  - A qualitative anthropological study in Gondar region, northwestern Ethiopia,
      revealed a very striking difference in cultural patterns of defecation in the two
      sexes which coincided with a high male/female ratio (16.5:1) of sigmoid volvulus
      morbidity in the regional hospital. Adult males show very irregular bowel
      behaviour, with bowel motions varying from zero to four per day. Irregular bowel
      behaviour in males, combined with the population's consumption of high fibre
      diets producing flatus and bulky stools, appears to overload the sigmoid colon,
      which elongates and dilates gradually, and subsequently undergoes volvulus
      occasionally. In women, on the other hand, the custom of limiting defecation to
      dawn and dusk is strictly adhered to and this regularity of bowel movements seems
      to protect them from overloading of the sigmoid colon and its consequences,
      despite their consumption of similar diets. In conclusion, it is believed that
      the high male/female ratio in sigmoid volvulus morbidity in Gondar region appears
      to be connected to gender specific patterns of defecation.

PMID- 8553445
TI  - Sigmoid volvulus among Africans in Durban.
AB  - The pattern of presentation and management of 90 patients treated for sigmoid
      volvulus over a 7-year period was studied. There was a 9:1 male preponderance and
      64% were under 50 years of age. Intestinal obstruction was the presenting feature
      in 84%, while the rest presented with acute abdomen or pain. Unlike other African
      series, this constituted only 8% of intestinal obstruction. Sixty-one per cent
      were managed by sigmoidoscopic decompression and semi-elective sigmoidectomy, and
      30% had an emergency operation. A primary anastomosis was undertaken in 71% while
      others, mainly emergency cases, had a temporary colostomy. There was a 20%
      morbidity and 12% mortality, 80% of which was in the emergency operation group.
      It is concluded that the pattern of sigmoid volvulus among Durban Africans
      differs from that reported in other African countries where young males
      predominate, and from that in Western societies with elderly female
      preponderance. When volvulus necessitates emergency surgery, it carries a
      substantial mortality even in relatively young patients and therefore we advocate
      resection in all patients during the same hospital admission even in those whose
      torsion is easily reduced at sigmoidoscopy lest a recurrence fails to reduce.

PMID- 8553446
TI  - Falciparum malaria presenting as psychosis.
AB  - A 15-year-old male presented on three occasions with fever, aggressive behaviour,
      poor sleep and mixed affective and schizophreniform symptoms in association with
      falciparum malaria. The symptoms resolved promptly following anti-malarial
      treatment. Prophylaxis with proguanil prevented recurrence of the illness.

PMID- 8553447
TI  - Severe myoclonus in a patient recovering from falciparum malaria.
AB  - Isolated myoclonus has rarely been reported as a complication of Plasmodium
      falciparum malaria. We describe the development of chaotic myoclonic jerks in an
      afebrile and conscious patient, the fourth day of treatment with quinine for P.
      falciparum infection. The myoclonus finally resulted in a generalized tonic
      clonic seizure and coma, which resolved without further antimalarial treatment.

PMID- 8553448
TI  - Steroid dependent neurocysticercosis.

PMID- 8553449
TI  - Reversal of amenorrhoea after Mectizan treatment.
AB  - Plausible reversal of secondary amenorrhoea in three women infected with
      onchocerciasis after Mectizan treatment in Imo State, Nigeria, is presented. The
      women aged 30, 28, and 32 years with drastic reduction in mean microfilaria
      scores had reversed amenorrhoea 8, 13 and 10 days post Mectizan treatment,
      respectively. They had typical manifestation of onchocerciasis including nodules,
      pruritic rash, body itching and musculo-skeletal pains. The manifestations eased
      off 4 days post treatment. The plausible link between loss of fertility due to
      premature menopause in women and onchocerciasis is discussed.

PMID- 8553450
TI  - Cryptococcal meningitis and confusional psychosis. A case report and literature
      review.
AB  - A previously healthy and immuno-competent 22-year-old man presented in
      confusional psychosis. Cryptococcal meningitis was later found to be the
      underlying cause as proven by culturing Cryptococcus neoformans serotype A from
      the cerebrospinal fluid. Combined antifungal therapy with amphotericin B and 5
      fluorocytosine resulted in sustained improvement of all mental and physical
      functions. Cryptococcosis has rarely been reported from the Middle East. This
      represents the second case from Kuwait.

PMID- 8553451
TI  - An unusual differential diagnosis of myringitis bullosa haemorrhagica.

PMID- 8553452
TI  - Spontaneous perforation of the bladder. A report of two cases.
AB  - Rupture of the urinary bladder which is not associated with instrumental or
      external trauma is uncommon. Two cases of spontaneous bladder perforation were
      seen in a district general hospital in the Ashanti region, Ghana. Both cases
      presented with the primary clinical picture of an acute abdomen suggestive of a
      ruptured viscus. At laparotomy pin-point perforations of the bladder were found
      to exist. The literature is reviewed with particular reference to the possible
      pathogenesis within a tropical setting.

PMID- 8553453
TI  - More severe disease course and higher mortality in Jamaican patients with lupus
      erythematosus (SLE)

PMID- 8553454
TI  - Visceral leishmaniasis.

PMID- 8553455
TI  - [The clearance function of the bronchial epithelium].
AB  - Modern literature is reviewed in terms of different views on cytological basis of
      clearing function of the bronchial epithelium, on the whole, and of its separate
      parts. Different factors influencing the mucociliary clearance are described. The
      necessity to elaborate some better, more objective methods of clearance
      disturbances diagnosis is emphasized. Principal attention is paid to regenerative
      restorative processes, which normally occur in the bronchial epithelium, and to
      expediency of influencing them.

PMID- 8553456
TI  - [The ultrastructure of the epithelial endocrinocytes of the appendiceal mucosa in
      the human fetus].
AB  - An electron microscope study of the epithelium of vermiform processes of 11-26
      week old human fetuses showed seven types of endocrinocytes differing in
      ultrastructure and dimensions of secretory granules. In addition to the six known
      types of endocrinocytes (EC, D, D1, I, L and P), endocrinocytes of a 7th type
      were discovered which are beyond the International classification of
      endocrinocytes of the gastroenteropancreatic system. The overwhelming majority of
      endocrinocytes of the vermiform process epithelium form EC-cells. Besides, cells
      of a "mixed" type, both exo-endocrine and endo-endocrine cells, were revealed.

PMID- 8553457
TI  - [The rapid assessment of the morphofunctional status of preimplantation mouse
      embryos at the moment of explantation during cultivation and development in
      vitro].

PMID- 8553458
TI  - [The stimulation of pulmonary epithelial regeneration and of the clearance
      function of the mucociliary apparatus by using bemetil].
AB  - A method of stimulation of the bronchial epithelium regeneration and mucociliary
      apparatus function is described. The effect is achieved with the help of
      bemithyl, an agent of the actoprotector group. In combination with
      immunocorrection, this effect is potentiated. The method is quite simple and may
      be extensively used in experimental investigations and clinical practice.

PMID- 8553459
TI  - [The protective effect of the nerve growth factor on sensory neurons in
      organotypic culture under the action of diphtheria toxin].
AB  - Diphtheria toxin (1.10(-1) - 1.10(-6) Lf/ml) was found to inhibit neurite
      extension in chick embryo dorsal root ganglia in vitro. If the nerve growth
      factor (60 ng/ml) was added with the toxin to culture media, the effect of
      diphtheria toxin was seen to decrease and the neurite outgrowth was compared with
      control. Protective effect of nerve growth factor estimated by the influence of
      diphtheria toxin may be used for new principles of diphtheria treatment.

PMID- 8553460
TI  - [The effect of prolactin on DNA synthesis in cultured bovine granulosa cells].
AB  - The influence of bovine prolactin (BPL) on DNA synthesis in cultured cow
      granulosa cells in various media has been studied. BPL exerted a mitogenic effect
      on granulosa cells of follicles 3-5 mm in diameter, with the effect depending on
      hormone concentration in the cultural medium. In the medium with bovine growth
      hormone the maximum effective concentration of BPL was 100 times more than in
      other used media. The degree of BPL influence on granulosa cell proliferation
      depended on the degree of cell differentiation. In cultures of granulosa cells
      taken from follicles 1-2 and 3-5 mm in diameter, while the BPL concentration
      increased from 500 ng/ml to 5 micrograms/ml in the serum free medium, and from 50
      ng/ml to 500 ng/ml in the medium with 5% fetal bovine serum, the stimulation of
      DNA synthesis in cells decreased. The growth-promoting influence of BPL on
      granulosa cells of follicles 6-10 mm in diameter did not depend on its
      concentration in the cultural medium. The maximum mitogenic hormonal effect
      decreased with the growth of a follicle. This fact is in accord with the recent
      notions of a progressive reduction of granulosa cell proliferative activity
      during follicular maturation. The results obtained are discussed in terms of a
      hypothesis that prolactin can influence granulosa cell secretion of a regulator
      of meiosis and folliculogenesis, i.e. an inhibitor of oocyte maturation.

PMID- 8553461
TI  - [A comparative study of the synthesis of membrane hetero-organic antigens of
      kidney origin on tissue slices and isolated cells after a single carcinogenic
      exposure in rats].
AB  - A comparative study was carried out of a single carcinogenic injection of rats
      with a "weak" carcinogen, 4-dimethylaminoazobenzene (DAB), and a "strong"
      carcinogen, N-diethylnitrozamine (DENA). Both carcinogenic agents caused similar
      antigenic rearrangements involving the appearance of membrane hetero-organic
      antigens of kidney origin associated with the Zajdela hepatoma on the hepatocyte
      membrane. The expression of these antigens is longer in DENA carcinogenesis. On
      the sections of embryonic liver (16-18 days) single hepatocytes were discovered
      carrying membrane hetero-organic antigens. No synthesis of these antigens was
      discovered in cells of the definitive liver, but it was seen to resume at early
      stages of carcinogenesis. Quantitative characteristics of synthesis of the
      investigated antigens was done by means of immunocytofluorometric method using
      membranes of isolated hepatoma cells and hepatocytes of rats after a single
      carcinogenic injection and partial hepatectomy.

PMID- 8553462
TI  - [Extracellular DNA in the blood of pregnant women].
AB  - The level of extracellular DNA increases in the blood of women during pregnancy.
      By means of PCR, the full-size Alu repeats were observed among extracellular
      blood DNA repeats of pregnant women. Furthermore, with Tc65 type primer the PCR
      method allowed to observe in the blood DNA fragments flanked by inverted Alu
      repeats (inter Alu repeats). The presence of such a type of inter Alu repeats was
      estimated in the blood of women being in the first trimester of pregnancy only,
      but was not estimated among blood DNA fragments of women of the last trimester of
      pregnancy. It is discussed which types of cells may serve as a source of
      extracellular blood DNA (either trophoblast cells, lymphocytes, or decidual
      cells), the significance of such DNA for pregnancy being appreciated.

PMID- 8553463
TI  - [A disorder in the energy-conversion processes in the liver mitochondria of rats
      under the action of sanguinarin and AFMA].
AB  - Processes of energy transduction were studied in isolated rat liver mitochondria,
      taken as a possible target for DNA intercalators, which differs from a usual one,
      associated with nucleic acid metabolism reactions. In the mitochondrial
      suspension, changes in respiration rates and latent ATPase activity in controlled
      state were defined in addition to a decrease in respiratory control index (V2/V1)
      and P/O ratio under the influence of DNA intercalators, benzophenanthridine
      alkaloid sanguinarine and acridine derivative APhMA. Within the range of examined
      sanguinarine and APhMA concentrations, the increase in respiration rate and
      activation of latent ATPase activity of mitochondrial suspension was first
      determined, with the maxima of these activities at 10(-4) M for both the agents.
      A further increase in sanguinarine and APhMA concentrations caused the inhibition
      of these reactions. Such dose-dependent shapes, with a maximum for the curves of
      mitochondrial respiration rate and ATPase activity "bell-shaped"), are typical
      for the majority of so far known uncouplers of oxidative phosphorylation in
      mitochondria. The fall of V2/V1 and P/O, under the influence of sanguinarine and
      APhMA, evidenced for the inhibition of ATP synthesis in mitochondria. The
      mechanism of uncoupling by sanguinarine and APhMA was supposed to differ from
      that by protonophores. It has been suggested that the uncoupling of oxidative
      phosphorylation by sanguinarine and APhMA was associated with the ability of
      these organic cations to neutralize negative charges near the external side of
      energized internal mitochondrial membranes. Correlation between the capacity for
      DNA intercalation and that for the energy transfer inhibition in mitochondria of
      these two agents is presumably based on the importance of positive charges and
      hydrophobic interactions, both for intercalation into polynucleotide double
      helices and for negative charges neutralization in energized mitochondrial
      membranes. Among DNA intercalators, so far examined, no agent has been
      established, which would not disturb the coupling of respiration and
      phosphorylation in mitochondria. However, there is no strong correlation for the
      agents between the ability to intercalate into DNA double helix and to disturb
      the energy transfer processes in mitochondria. Sanguinarine, which is more
      potent, as a DNA intercalator, than APhMA, is weaker than APhMA as an uncoupler
      of mitochondrial oxidative phosphorylation. For DNA-intercalation, the steric
      conformity between sizes of the intercalator molecule and of DNA base pairs is of
      great importance. On the other hand, for mitochondrial energy transfer
      disturbance, the agent ability to achieve sites of negative charges in the
      energized inner membranes is more significant.

PMID- 8553464
TI  - [Effect of catechins and proanthocyanidins on the initial stage of protein
      biosynthesis].
AB  - Catechins and proanthocyanidins have been studied for their effect on initial
      stage of the protein biosynthesis. It has been found that (+)-catechin in all
      concentrations studied does not influence the intensity of t-RNA aminoacylation
      by 14C-glycine and 14C-arginine. Proanthocyanidins, namely, dimers B-3, B-6 and
      trimer C2 in the concentration of 10(-3) M completely inhibit the initial stage
      of the protein biosynthesis.

PMID- 8553465
TI  - Stoichiometry of pectin and glucose fermentation in Prevotella ruminicola.
AB  - Prevotella ruminicola is an important rumen pectinolytic bacterium. Strain 659
      was grown anaerobically at pH 6.5 and temperature 39 degrees C in LF2 fermenters
      on media containing glucose or pectin (4 g/l) in order to determine its
      fermentation stoichiometry and growth parameters. Both substrates were utilized
      almost completely (> 90%). The growth on pectin was more rapid than on glucose.
      Pectin and glucose differed considerably in composition of fermentation end
      products. Production of acetate was significantly higher when P. ruminicola 659
      was grown on pectin, while production of other metabolites (formate, succinate,
      lactate) was lower than on glucose. Production of dry cell matter was
      significantly higher in cultures supplied with glucose. An increase in dry matter
      and protein yields calculated per carbon was not verified.

PMID- 8553466
TI  - [Structural-functional features of factor VIII (FVIII) and its role in the
      cascade system of blood coagulation].
AB  - Functions and structure of FVIII which is a cofactor in the internal way of blood
      coagulation are described as well as the known activation and inactivation
      mechanisms of FVIII following from its domain structure. The effect exerted by
      the Willibrandt factor (Wf), thrombin, factor X alpha(FX), activated protein
      C(APC) on the FVIII functions and interrelation between internal and external
      ways of blood coagulation in FVIII activation are discussed. The homologous
      structure of factors V and VIII which is a result of their cofactor action is
      described.

PMID- 8553467
TI  - [The amino acid pool of the liver during activation of glutathione synthesis].
AB  - Regularities of formation of a pool of free amino acids and their derivatives in
      the liver of rats were studied during L-2-oxothiazoidin-4-carboxylate-induced
      glutathione synthesis activation. It was shown that an increase in concentrations
      of sulfur-containing (cysteate, cysteine) and branched-chain (valine, isoleucine,
      leucine) amino acids was the most typical change. The correlation and linear
      discriminant analysis of the whole range of the compounds studied in the dynamics
      of the experimental process has proved high informativeness of glycogenic amino
      acid levels, activation of the whole chain of synthesis and degradation of thiol
      containing amino acids as well as determination of the obtained shifts in
      concentrations of reduced glutathione.

PMID- 8553468
TI  - [Kinetic regularities of thermal inactivation of superoxide dismutase].
AB  - An interest to the study of superoxide dismutase (SOD) is growing as it has
      become known that this enzyme may be used as a medical preparation and in the
      biochemical research. The aim of the work presented is to investigate the
      influence of temperature and UV radiation on the structural-functional properties
      of SOD. Copper- and zinc-containing SOD from bovine erythrocytes with the light
      of a DRT-400 lamp (dose of irradiation 1.5 x 10(3) J/m2) through an UFS-1 light
      filter (240-390 nm). The influence of temperature (20-85 degrees C) on the
      functional properties of native and UV modified SOD has been studied. The process
      of thermodenaturation of the enzyme proceeds at least two consecutive stages. SOD
      is stable within the temperature interval 20-70 degrees C. Kinetics of
      thermodenaturation of protein has been studied. It was established that UV light
      increases enzyme thermostability. Changes found in the kinetic characteristics of
      the UV-irradiated SOD are apparently due to its conformational rearrangements.

PMID- 8553469
TI  - [Role of nicotinic acid and its derivatives in disorders of nervous system
      function].
AB  - Participation of nicotinic acid and its derivates in the functioning of nervous
      system is considered basing on the data from literature. It is supposed that the
      favourable therapeutic effects of nicotinamide, nicotinic acid and their active
      biological form--NAD are realized due to the mechanisms of their functioning in
      the nervous system, for treating schizophrenia, epilepsy and other diseases of
      the nervous system.

PMID- 8553470
TI  - [Identification of repetitive sequences and internal symmetry in primary
      structure of yeast GDP-Man:Dol-PP-GlcNAc2 mannosyltransferase].
AB  - Segments of the amino acid sequence containing a large number of internal
      symmetry centres were identified in the primary structure of enzyme GDP-Man:Dol
      PP-GlcNAc2 mannosyltransferase (gene ALG1 product of yeast) by means of a
      comparative analysis of amino acid codon roots (AACR). The highest density of
      symmetric segments was discovered in the AlG1 N-terminal hydrophobic segment
      which is responsible for the enzyme anchoring in the membrane and contains a
      dolichol-binding sequence, and is one of the central (104-195) and C-terminal
      (310-439) segments of ALG1. Amino acid sequences 104-195 and 310-439, on the one
      hand, are structurally similar to carbohydrate-binding proteins (lectins) and so,
      may participate in formation of the catalytic enzyme centre that interacts with
      carbohydrate-containing substrates, GDP-mannose and Dol-PP-GlcNAc2, and, on the
      other hand, they are able to form some alpha-helices. These data agree with the
      supposition about evolutionary conservation of the symmetric structures in
      molecular segments of proteins, which determine their functional activity. The
      graphic method of the AACR sequence analysis suggested by the authors has
      permitted identifying repeating homologous sequences of 18-20 amino acids in the
      enzyme molecule. They are a result of DNA sequence duplication and multiplication
      in evolution. Moreover, two long segments (305-357 and 376-430) possessing (after
      alignment of their amino acid sequences) 21% identical and 64% equifunctional
      amino acid residues were found in the C-terminal region of ALG1. These data,
      probably, testify to duplication of the nucleotide sequence, coding these
      segments.

PMID- 8553471
TI  - [Interactions of various cationic detergents with cholinesterase of horse blood
      serum].
AB  - Cetyltrimethyl ammonium and cetylpyridinium, both being cationic detergents, have
      been studied for their effect on the catalytic activity of horse blood serum
      cholinesterase (BuHChE) in reactions of hydrolysis of carbonic acid esters. It is
      shown that the detergents tested are reversible competitive inhibitors of the
      reaction of butyryl cholinesterase hydrolysis of butyryl choline, a specific
      cationic substrate, but in this case they activate enzymic hydrolysis of alpha
      naphthylacetate, a nonspecific neutral substrate. Values of constants, describing
      enzyme binding with a detergent, are estimated both by the degree of inhibition
      of enzymatic hydrolysis of butyryl choline and by the degree of activation of
      enzymatic hydrolysis of alpha-naphthylacetate and are practically equal. An
      assumption is made that in both cases the same complex of BuHChE with a molecule
      of the detergent is formed. The enzyme, as a constituent of such a complex,
      possesses different substrate specificity as compared with the initial one.

PMID- 8553472
TI  - [Alanine dehydrogenase of the cyanobacterium Plectonema boryanum in the early
      period of cyanophage LPP-3 development].
AB  - It has been studied how reproduction of LPP-3 in Plectonema boryanum cells
      influences the alanine dehydrogenase activity. It has been found that immediately
      after the virus adsorption the enzyme activity falls by 50% and the anabolic
      reaction is blocked. Physicochemical properties of the enzyme vary as well. An
      infected cell has one isoenzyme-octamer with pl 9.1-9.2, pH-optimum by action 9
      10, molecular weight about 27 kDa.

PMID- 8553473
TI  - [Effect of ionizing radiation on membrane transport properties of small
      intestines].
AB  - The data on the effect of total X-ray irradiation (1.0; 2.0; 3.0 Gy) on transport
      of Ca2+ and L-phenylalanine by brush-border (BB) membranes of rat small intestine
      were obtained. The increase of uptake rate for Ca2+ by BB membrane preparations
      together with the enhancement of the process of L-phenylalanine passive diffusion
      and suppression of Na(+)-dependent transport of this amino acid was established.

PMID- 8553474
TI  - [Fibrin fragment beta 15-118. Inhibitory and complex-forming properties].
AB  - Peptide beta 15-118 isolated from desAABB-NDSK preserves fibrin polymerization
      active site "B", inhibits polymerization process at 12 degrees C, eliminates the
      inhibitory properties of plasmin D-D-fragment but does not influence inhibitory
      properties of a D-monomer fragment. Complex formation between peptide beta 15-118
      and both D- and D-D fragments was electrophoretically demonstrated. Peptide beta
      15-118 forms more stable complex with the D-D fragment which does not dissociate
      in the medium of polymerizing fibrin as the complex of the peptide with monomer D
      fragment does. Gel filtration data confirm dimerization of D-monomer fragments
      after their complexing with beta 15-118. This phenomenon suggests that mutual
      affinity of D-domains in fibrin increases after loci interactions of the "B"-"b"
      type.

PMID- 8553475
TI  - [Interaction between bee venom melittin and human blood albumin].
AB  - It is shown that bee venom melittin interacts with human blood albumin at pH 8.0
      8.5 in the presence of NaCl (concentration over 0.1%) and forms a precipitating
      complex (MA), the albumin/melittin ratio being 1:12 for the monomer melittin.
      With a decrease of pH down to 5.3 and salt concentration below the limit
      mentioned, the precipitate is destroyed. The complex is soluble in the distilled
      water. Conditions for carrying the precipitation reaction between albumin and
      melittin in agarose gel are chosen. The titration method has been used to
      determine that melittin is bound up with albumin in the molar ratio (10-12):1 for
      monomeric melittin or 3:1 for tetrameric melittin.

PMID- 8553476
TI  - [Acid-base equilibrium and nitrogen metabolism in rats in a state of artificial
      hibernation].
AB  - Experiments on rats have shown an important role of hypercapnia in the
      development of condition of artificial hibernation in combination with influence
      of hypothermia, hypoxia and hypercapnia. It is proved that the joint action of
      hypothermia, hypoxia and hypercapnia has induced development of respiratory
      acidosis and hibernation in animals, while removal of the hypercapnia effect has
      induced development of acute metabolic acidosis and death of animals. It has been
      found that animals in the state of artificial hibernation have considerable
      changes in concentrations of main electrolytes (Na+, K+, Ca+, Mg2+, phosphates,
      Cl-) and metabolites (NH3, glutamine, urea) in blood as well as in activity of
      enzymes (glutamaldehydrogenase, glutaminase, arginase) in tissues of the liver
      and kidneys.

PMID- 8553477
TI  - [Determination of the general prothrombin level and detection of its functionally
      inactive forms using the enzyme ecamulin purified from Echis multisquamatus
      venom].
AB  - The method for determination of the general prothrombin level and detection of
      its inactive forms (prothrombin-1, decarboxylated prothrombin, etc.) has been
      worked out. Enzyme ecamulin was purified from the venom of Echis multisquamatus.
      Ecamulin test was used for plasma of practically healthy people and patients with
      hypertension. The results obtained proved that this test is informative and
      precise. Comparison of two tests, prothrombin and ecamulin ones, permits
      characterizing the state of blood coagulation and finding functionally inactive
      prothrombin forms which are the markers of some pathological states.

PMID- 8553478
TI  - [Effect of zinc-metallothionein on lipid peroxidation in blood plasma and in
      mouse liver in acute alcoholic intoxication].
AB  - The reduction of malondialdehyde (MDA) content in mouse blood plasma and liver 1h
      1 day after the acute ethanol poisoning (3 g/kg) was discovered. Rat liver zinc
      metallothionein in a dose 2 mg/kg inoculated before the alcohol introduction
      restored the MDA level to norm; at the same time the mixture which modulated this
      protein (albumin, cysteine and zinc) had only the tendency to normalization of
      the MDA level. On the third day after the poisoning in all cases the 2-2.5 times
      increase of the plasma MDA level was shown, but the liver MDA content did not
      change in comparison with the control. The number of the possible explanation of
      reduction of plasma lipid peroxidation level in the early time after the ethanol
      poisoning was proposed (hypoxy, aldehyde dehydrogenase activation etc.). It is
      supposed that zinc-metallothionein influence is connected with its capacity to
      inactivate acetaldehyde.

PMID- 8553479
TI  - [Antioxidant activity of the drug distinol in vitro].
AB  - Distinol, ionol and dimethylsulphoxide were investigated in model reaction of
      thermal oxidation of methyl oleate for their antioxidant activity and for their
      influence on the rate of malonic dialdehyde formation in the liver tissue of
      chicken with E-hypovitaminosis in vitro. It has been found that the level of
      antioxidant activity in the homogeneous system of methyl oleate oxidation permits
      arranging the preparations studied in a series: ionol > distinol >
      dimethylsulphoxide. Distinol inhibits peroxidation of lipids in the liver
      homogenates of chicken most efficiently. Its inhibitory effect is 4.6 times
      higher than that of dimethylsulphoxide and 1.3 times higher than that of ionol.
      No correlation was found between antioxidant activity of distinol in the
      homogeneous model system and its influence on peroxidation of lipids in
      biomembranes.

PMID- 8553480
TI  - [Anti-edematous action of EDTA, its effect on lipid peroxidation intensity and
      various components of the antioxidant system of the lungs in rats exposed to
      NO2].
AB  - It has been studied how preventive administration of EDTA influences toxic NO2-
      induced pulmonary edema and disturbances in antioxidant systems. The compound in
      question, being preventively administered, has exerted a significant antiedematic
      effect as a result of a decrease in lipid peroxidation intensity and protection
      of the most important substrate components of the nonenzymatic antioxidant system
      from the oxidation effect.

PMID- 8553481
TI  - [Gas chromatographic determination of individual high molecular weight fatty
      acids in the composition of lipids].
AB  - A rapid and precise method is suggested for quantitative determination of highly
      molecular fatty acids in a sample either in the esterified (mono-, di- and
      triglycerides, cholesterol ethers, and phospholipids) or in the non-esterified
      state, as well as like salts of fatty acids (soaps). Methyl ethers of fatty acids
      have been obtained by immediate methanolysis of the sample studied. The method
      advantages are both indices of the amount of the internal standard added to the
      sample of concern and possibility to determine highly molecular fatty acids in
      any sample taken either from plants or from animals.

PMID- 8553482
TI  - [Comprehensive laboratory diagnosis of intravascular blood coagulation syndrome
      in late gestosis].
AB  - A chronic form of intravascular blood coagulation (the DIC syndrome) is an
      obligatory pathogenetic mechanism in the organism of pregnant women with late
      gestoses. In order to find the DIC-syndrome and to provide urgent protective
      measures comprehensive laboratory diagnostics of the hemostatic pathologies is
      necessary. Analysis of clinician data has shown an optimal quantity and sequence
      of tests, among which some are traditional and several have been worked out by
      the authors. This approach can be recommended for corresponding medical
      institutions as such that provides obtaining exact and informative data about the
      state of blood coagulation with minimal amounts of human plasma.

PMID- 8553483
TI  - [Manipulation of frozen shoulder?].

PMID- 8553484
TI  - [Frozen shoulder. Arthroscopy and manipulation in general anesthesia, followed by
      early passive mobilization].
AB  - Over a 15 month period 20 patients with 20 arthroscopically verified frozen
      shoulders were treated with manipulation under general anaesthesia and early
      passive motion. The study had a minimum of six months follow-up. The average
      duration of the disease before treatment was eight months. Prior to treatment all
      patients suffered from moderate to severe pain and the average range of motion
      was less than 40% of the normal shoulder. During the follow-up period 55% had
      obtained a normal or almost full range of motion and 75% suffered from only
      slight pain or had no pain at all. Fourteen patients returned to prior work
      within a mean of nine weeks after treatment. We found no relation between the end
      result and the prior pathology. We believe that manipulation with arthroscopy is
      an effective way of shortening the course of an apparently self-limiting disease
      and should be considered when conservative treatment fails.

PMID- 8553485
TI  - [Obstructive sleep apnea syndrome].

PMID- 8553486
TI  - [Progressive myoclonic epilepsy].
AB  - Progressive myoclonic epilepsy (PME) is a syndrome characterized by myoclonias,
      epilepsy, progressive dementia and other neurological deficits. PME may be caused
      by various, rare, incompletely elucidated genetic diseases, and is characterized
      by age at onset, duration, clinical and pathoanatomical abnormalities. There is
      ethnic and geographic variation in the frequency of the syndrome. The diseases
      are frequently autosomal recessive. Research in PME leads to a better
      understanding of the neurobiological processes of epilepsy. PME should be
      considered in cases of severe myoclonic epilepsy, progressive neurological
      disability and poor effect of antiepileptic treatment, and biopsies from skin,
      mucosa or muscle should be performed. Centralization of treatment of these rare
      diseases is recommended.

PMID- 8553487
TI  - [Quality of psychiatric treatment. Determined by patient satisfaction].
AB  - Patient satisfaction with inpatient and outpatient psychiatric treatment in a
      community-oriented care organization was studied. The study included 155
      psychiatric patients, who were invited to participate in a semi-structured
      interview one year following their first admission to a psychiatric hospital. The
      response rate was 65%. The patients were asked to evaluate the treatment provided
      during the first year following the first day of their admission. The level of
      satisfaction varied for different aspects of treatment. It was high with regard
      to global improvement, general satisfaction, and participation of relatives and
      low with regard to the quality of inpatient-care, extent of aftercare,
      coordination between services, information and influence on treatment. In the
      open-ended questions many patients expressed dissatisfaction with the amount of
      time available with the caregivers, especially the doctors. In general,
      satisfaction with specific areas of treatment was related to overall
      satisfaction.

PMID- 8553488
TI  - [Validity of the diagnosis "essential hypertension" in the National Patient
      Registry].
AB  - This study validated hypertension (ICD-8: 401.99) in The National Inpatient
      Register with reference to the use of the diagnosis in the Occupational
      Hospitalization Register. A university hospital and a regional hospital were
      chosen for the evaluation. A sample of case records with the discharge diagnosis
      essential hypertension and additional case records with other diagnoses were re
      coded blindly and independently by two doctors. Cause of admission or admission
      diagnosis was recorded for essential hypertension cases. The agreement with The
      National Inpatient Register ranged from 60 to 40%. About half of the cases with
      the discharge diagnosis "essential hypertension" were admitted to hospital due to
      hypertension, about a quarter due to diagnoses within "other arteriosclerotic
      diseases" (ICD-8: 400, 402-440). The misclassification may lead to an
      underestimation of risks of hypertension in various occupations in the
      Occupational Hospitalization Register or bias the occupational risk pattern of
      essential hypertension to become more alike that of arteriosclerotic diseases.

PMID- 8553489
TI  - [Measurement of the ear temperature at a department of surgery].
AB  - Tympanic measurement of body temperature with FirstTemp tympanic thermometer was
      compared with mercury rectal thermometers in 155 adult patients in a department
      of abdominal surgery. The tympanic thermometer did not correlate well with the
      mercury rectal thermometer with a correlation coefficient of 0.70. The median
      rectal temperature differed from the median tympanic temperature by 0.34 degree
      C, a factor which could be corrected by changing the temperature shown on the
      display from the "oral" mode into the 0.40 degree C higher rectal "mode". Care
      should be taken not to measure the temperature in an ear, on which the patient
      has been lying recently.

PMID- 8553490
TI  - [Brodie abscess. Primarily misinterpreted as traumatic lesion].
AB  - Two case histories are presented. In the first, a 49 year-old man fell on his
      right hip. He was able to walk, but because of pain he came to our emergency
      room. Radiographics gave an impression of an undislocated intertrochanteric
      fracture, scintigraphy confirmed the suspicion. There were no signs of infection.
      On starting osteosynthesis with the drilling of a hole in the lateral cortex,
      discharge of pus was observed and curettage of the abscess cavity was performed.
      In the second, a 21 year-old man hit his right knee against a table. Because of
      pain he was admitted to hospital. Primary signs of a lesion of the lateral
      meniscus were found and arthroscopy was scheduled. When readmitted we found signs
      of an infection and X-ray revealed a Brodie's abscess in the proximal tibia. The
      abscess cavity was opened and curettage was performed. Radiographics,
      scintigraphics, blood parameters and pathological and microbiological
      investigations revealed primary chronic osteomyelitis in both patients.
      Antibiotic therapy was instituted and six weeks after primary operation bone
      transplantation was performed. The further course was uncomplicated.

PMID- 8553491
TI  - [Bacillary angiomatosis, cat-scratch disease and trench fever: are these diseases
      caused by the same bacteria?].

PMID- 8553492
TI  - [Combination therapy of HIV].

PMID- 8553493
TI  - [Unacceptable aggressive marketing].

PMID- 8553494
TI  - Computer analysis of the early diastolic notch in Doppler sonograms of the
      uterine arteries.
AB  - This article describes a set of processing and analysis techniques for automated
      identification and quantification of the early diastolic notch (EDN), a feature
      of Doppler sonograms from the uterine arteries which has been associated with
      adverse pregnancy outcomes such as preeclampsia and intrauterine growth
      retardation. Examples covering different sonogram types are provided to
      illustrate the effectiveness and reproducibility of the processing/analysis
      tools. Also, a receiver-operating characteristic-based evaluation of the EDN
      quantification and pulsatility indexes is presented, which examines the ability
      to predict hypertension and/or intrauterine growth retardation, using a set of
      uterine Doppler sonograms from 92 patients acquired at 18 weeks of gestation. In
      summary, the ROC results confirm the link between the EDN and abnormal pregnancy
      outcomes, and suggest that EDN quantification has a higher diagnostic accuracy
      than the pulsatility index, which characterises the flow waveform in a global
      manner and therefore does not take explicitly into account the localised nature
      of the EDN. Quantification of the EDN at 18 weeks of gestation appears to best
      predict the most severely abnormal pregnancy outcomes.

PMID- 8553495
TI  - Quantification of color Doppler for the evaluation of tissue vascularization.
AB  - Assessment of tissue vascularization with color Doppler (CD) can improve
      differential diagnosis of tumors. Until now, measurement of flow velocities is
      restricted to conventional duplex ultrasound of single vessels or
      semiquantitative scoring of the vessel distribution in CD. We developed a new
      method for quantification of CD data in organs or tumors by statistical image
      analysis. Based on standardized image recording, data is acquired from the video
      output of any ultrasound scanner using a 24-bit color framegrabber in a personal
      computer. The digitized colors are recognized according to their position in the
      CD palette bar resulting in an 8-bit color image (number of identified pixels >
      99.9%). Within the region of interest, statistics of the detected flow patterns
      are calculated. The color pixel density and the mean color value varies between
      recordings of the same image during subsequent systolic peaks with a SD of 10%
      and 2%, respectively, and within different sections of the same organ or tumor
      with 25% and 10-50%. This analysis can be used for comparative or longitudinal
      studies and an objective evaluation of CD in complex vascular formations such as
      tumors. Its diagnostic impact has already been demonstrated in clinical studies.

PMID- 8553496
TI  - Transesophageal color Doppler evaluation of obstructive lesions using the new
      "Quasar" technology.
AB  - Due to the unavoidable problem of aliasing, color flow signals from high blood
      flow velocities cannot be measured directly by conventional color Doppler. A new
      technology termed Quantitative Un-Aliased Speed Algorithm Recognition (Quasar)
      has been developed to overcome this limitation. Employing this technology, we
      used transesophageal color Doppler echocardiography to investigate whether the
      velocities detected by the Quasar would correlate with those obtained by
      continuous-wave Doppler both in vitro and in vivo. In the in vitro study, a 5.0
      MHz transesophageal transducer of a Kontron Sigma 44 color Doppler flow system
      was used. Fourteen different peak velocities calculated and recorded by color
      Doppler-guided continuous-wave Doppler were randomly selected. In the clinical
      study, intraoperative transesophageal echocardiography was performed using the
      same transducer 18 adults (13 aortic valve stenosis, 2 aortic and 2 mitral
      stenosis, 2 hypertrophic obstructive cardiomyopathy and 1 mitral valve stenosis).
      Following each continuous-wave Doppler measurement, the Quasar was activated, and
      a small Quasar marker was placed in the brightest area of the color flow jet to
      obtain the maximum mean velocity readout. The maximum mean velocities measured by
      Quasar closely correlated with maximum peak velocities obtained by color flow
      guided continuous-wave Doppler in both in vitro (0.53 to 1.65 m/s, r = 0.99) and
      in vivo studies (1.50 to 6.01 m/s, r = 0.97). We conclude that the new Quasar
      technology can accurately measure high blood flow velocities during
      transesophageal color Doppler echocardiography. This technique has the potential
      of obviating the need for continuous-wave Doppler.

PMID- 8553497
TI  - Correction of intrinsic spectral broadening errors in Doppler peak velocity
      measurements made with phased sector and linear array transducers.
AB  - Commercial duplex ultrasound systems primarily measure peak velocity of blood
      flow to provide important information in diagnosing vascular disease. However,
      due to errors caused by intrinsic spectral broadening (ISB), the accuracy
      decreases as the Doppler angle increases. In general, vascular technologists and
      surgeons keep the Doppler angle under 60 degrees. Even at 60 degrees, ISB can
      produce an overestimation of peak velocity as high as 40%. This would indicate
      the necessity of reducing the Doppler angle even lower than 60 degrees. Since
      most vessels in the body run parallel with the skin surface any criteria
      requiring a Doppler angle of say 45 degrees or less would be difficult to
      achieve. Using the transverse Doppler equation as a correction for ISB, in
      conjunction with the classical Doppler equation, accurate peak velocity
      measurements were obtained at Doppler angles as high as 80 degrees. Corrections
      were made using both phased sector and linear array transducers for steered and
      unsteered beams. However, for beams steered at large angles, 20 degrees or more,
      corresponding to Doppler angles of < 70 degrees, the transverse Doppler equation
      failed to correct ISB errors in measurements made. This may be due to the
      experimental setup and not due to limitations in the transverse Doppler equation.

PMID- 8553498
TI  - Volume flow estimation using time domain correlation and ultrasonic flowmetry.
AB  - A comparison of two volumetric blood flow measurement techniques, CVI-Q (based on
      time domain correlation) and ultrasonic flowmetry, has been performed in vitro
      and in vivo. A pulsatile flowpump was used to simulate carotid and femoral type
      waveforms which were measured simultaneously using the two methods. Five dogs had
      their common carotid and femoral arteries exposed, and the instantaneous maximum
      volume flow and the mean flow were measured. Each vessel was partially occluded
      halfway through the experiment, simulating a 90% stenosis. In vitro, both
      techniques achieved absolute errors below +/- 5% for flow rates over 100 mL/min,
      but ultrasonic flowmetry had statistically significant larger errors for slower
      flow rates. In vivo correlation coefficients ranging from 0.73 to 0.95 were
      obtained with regression line slopes close to unity. The two techniques were in
      reasonable agreement, but with standard deviations of 20% to 28%. These studies
      indicate that noninvasive CVI-Q measurements of blood flow in the carotid and
      femoral arteries are linear and accurate compared to invasive ultrasonic
      flowmetry.

PMID- 8553499
TI  - A theory to correct the systematic error caused by the imperfectly matched beam
      width to vessel diameter ratio on volumetric flow measurements using ultrasound
      techniques.
AB  - When a multigate procedure is used to measure volumetric flow in vessels, in
      addition to the flow rate result obtained from the conventional velocity profile
      method, a second result from an "average velocity profile method" can be obtained
      simultaneously. The latter method obtains the flow rate from the product of the
      average velocity across the profile and the cross-sectional area of the vessel. A
      theoretical model has been used to study the effect of the beam width to vessel
      diameter ratio (BWR) on these two results, as well as a third flow rate result
      obtained from the uniform insonation method. A theory has been established to
      correct the systematic error caused by the imperfectly matched BWR associated
      with each method. It uses a correction factor and the difference between the
      results from the average velocity profile method and the velocity profile method
      to compensate for the systematic error. The relationship between an optimal
      correction factor and the BWR under different flow conditions has been studied.
      The results using the correction theory in this model show that if the estimated
      BWR is within +/- 0.1 from the actual BWR value, the theoretical error in
      volumetric flow estimation can be limited to within 6.5% for the entire range of
      BWR.

PMID- 8553500
TI  - Ultrasound contrast agents nucleate inertial cavitation in vitro.
AB  - Some ultrasound contrast agents contain stable bodies of gas, and this study was
      undertaken to determine if these agents could provide nuclei for inertial
      cavitation. Inertial cavitation was detected and assessed by the measurement of
      the sonochemical hydrogen peroxide after exposure to 2.17-, 2.95- or 3.8-MHz
      ultrasound. A noncavitating system was obtained by removing cavitation nuclei
      from the rotating tube exposure chambers by vacuum degassing, and from the
      phosphate-buffered saline medium by filtering. Albunex added at 10-2, 10-3 or 10
      4 dilutions, or Levovist added at 2 mg mL-1, 0.2 mg mL-1 or 0.02 mg mL-1 all
      initiated significant H2O2 production for 2.17-MHz ultrasound at 0.41 MPa or
      higher spatial peak pressure amplitude for 5 min exposure gated at 0.25 s on and
      off with 60-rpm rotation. Not rotating the tube virtually eliminated H2O2
      production. For 2.5-min continuous exposure, both agents initiated significant
      H2O2 production for 2.95-MHz exposure at 0.58 MPa or higher, but not for 3.8-MHz
      exposure up to 1.16 MPa. Bubble-based ultrasound contrast agents therefore appear
      to be able to provide nuclei for inertial cavitation in the rotating tube
      exposure system.

PMID- 8553501
TI  - Intestinal hemorrhage from exposure to pulsed ultrasound.
AB  - Threshold exposures for producing intestinal hemorrhage in mice were determined
      using focused sources operating at 0.7, 1.1, 2.4 and 3.6 MHz. The choice of pulse
      length (10 microseconds) and pulse repetition frequency (100 Hz) made the
      exposures diagnostically relevant, while at the same time, minimized possible
      thermal contributions to the mechanism of action of the ultrasound. Each animal
      was irradiated at four to five abdominal sites for 5 min per site. Suprathreshold
      lesions ranged from small petechiae to hemorrhagic regions extending 4 mm or more
      along the intestine, depending upon the exposure levels. Higher frequencies were
      less effective in producing intestinal hemorrhage than lower frequencies.
      Thermocouple measurements of temperature rise in the intestine during ultrasound
      exposure revealed temperature increments between 1 degrees and 2 degrees C at the
      highest exposure levels. The frequency dependence of the production of intestinal
      hemorrhage together with the observed limited heating is consistent with a
      cavitation-related mechanism of action of pulsed ultrasound.

PMID- 8553502
TI  - Hematologic and growth-related effects of frequent prenatal ultrasound exposure
      in the long-tailed macaque (Macaca fascicularis).
AB  - Prior investigations have shown that reduced birth weights and transient
      neutropenias result from frequent exposure of monkey fetuses to ultrasound. To
      further explore these findings, 26 animals were studied (16 exposed, 10 controls;
      "triple mode"; ATL Ultramark 9 with HDI; ISPTAd approximately 645 to 714 mW/cm2).
      Exposures were performed daily for 5 days each week from gestational days (GD) 21
      to 35 (5 min), three times weekly from GD 36 to 60 (5 min), then weekly from GD
      61 to 153 +/- 1 (10 min). Fetal blood samples (FBS) were collected for complete
      blood counts (CBCs), hematopoietic progenitor assay, circulating insulin-like
      growth factors (IGF-I, IGF-II) and binding proteins (IGFBP-3) (GD 120, 140, 153
      +/- 1). Animals were delivered by Cesarean section at term (GD 153 +/- 1), and
      body weights, morphometrics, CBCs, and bone marrow aspirates assessed at delivery
      and postnatally for 3 months. Fetal neutropenias were noted in exposed animals in
      addition to reduced circulating progenitors (colony forming unit-granulocyte
      macrophage [CFU-GM]). Growth of CFU-GM from bone marrow was exuberant at term,
      whereas circulating levels were diminished comparable to prenatal samples.
      Exposed animals were smaller at birth; marked reductions in IGFBP-3 were noted
      prenatally. These data suggest that frequent prenatal ultrasound exposure can
      transiently alter the neutrophil lineage, although these findings may be the
      result of enhanced margination and organ sequestration. Data also suggest that
      transient, altered growth patterns may be due to perturbations of the IGF axis.

PMID- 8553503
TI  - Errors in transrectal ultrasonic planimetry of the prostate: computer simulation
      of volumetric errors applied to a screening population: regarding Bangma et al.
      UMB 21 (1):11-16; 1995.

PMID- 8553504
TI  - Comparison of diastolic filling models and their fit to transmitral Doppler
      contours.
AB  - Anatomic/physiologic and kinematic mathematical models of diastolic filling which
      employ (lumped) parameters of diastolic function have been used to predict or
      characterize transmitral flow. The ability to determine model parameters from
      clinical transmitral flow, the Doppler velocity profile (DVP), is equivalent to
      solving the "inverse problem" of diastole. Systematic model-to-model and model-to
      data comparison has never been carried out, in part due to the requirement that
      DVPs be digitized by hand. We developed, tested and verified a computerized
      method of DVP acquisition and reproduction, and carried out numerical
      determination of model-to-model and model-to-data goodness-of-fit. The
      transmitral flow velocity of two anatomic/physiologic models and one kinematic
      model were compared. Each model's ability to fit computer-acquired and reproduced
      transmitral DVPs was assessed. Results indicate that transmitral flow velocities
      generated by the three models are 'graphically indistinguishable and are able to
      fit the E-wave of clinical DVPs with comparable mean-square errors. Nonunique
      invertibility of the anatomic/physiologic models was verified, i.e., multiple
      sets of model parameters could be found that fit a single DVP with comparable
      mean-square error. The kinematic formulation permitted automated, unique, model
      parameter determination, solving the "inverse problem" for the Doppler E-wave. We
      conclude that automated, quantitative characterization of clinical Doppler E-wave
      contours using this method is feasible. The relation of kinematic parameters to
      physiologic variables is a subject of current investigation.

PMID- 8553505
TI  - [Effectiveness of local magnetic field of the acoustic frequency in the treatment
      of patients with acute inflammatory diseases of the larynx].
AB  - The authors have tried alternative magnetic field of sound frequency in patients
      with acute inflammatory diseases of the larynx. The above modality proved highly
      efficient in view of its bacteriological, immunomodulating and detoxication
      actions at cellular level, which make the method promising in physiotherapy of
      acute inflammation.

PMID- 8553506
TI  - [Skin tumors of the face: experience in contact laser excision].
AB  - A clinical review is provided of 1558 neoplasm cases of facial skin new growth of
      different origin and site. The technique of YAG-Nd laser in contact mode
      application is described. Specific postoperative features are correlated with
      tumor extension, its histological type and site. In all the cases, except skin
      papillomatosis, there were no primary recurrences.

PMID- 8553507
TI  - [Regional metastasis of malignant tumors of the external acoustic meatus and
      middle ear].

PMID- 8553508
TI  - [Functionally sparing surgery in locally spread malignant maxillary tumors and
      the use of local chemotherapy].
AB  - 53 patients underwent functionally sparing operations which imply electrosurgical
      maxillectomy with alveolar process and hard palate left intact as well as eyeball
      preserving resections. At termination of the surgical intervention cyanoacrylate
      glue compounds incorporating cytostatics bleomycin or carminomycin were applied
      to the walls of the postoperative cavity. Maxillary alveolar process and hard
      palate were preserved when the tumor arose from maxillary posterior superior
      segments, ethmoidal labyrinth and upper nasal cavity. In orbital direction of the
      tumor spread the eyeball was spared when the lesion was confined to orbital wall
      and if intraorbital fat was uninvolved. 3-year survival after the above
      operations made up 60.4%. The method is believed oncologically effective and
      functionally, cosmetically sparing.

PMID- 8553509
TI  - [Initial experience in vascular plastic surgery in the surgical treatment of
      metastases of laryngopharyngeal cancer].
AB  - The paper concerns conduction of the internal carotid artery and internal jugular
      vein reconstruction in 3 and 2 patients, respectively, operated for metastases of
      laryngopharyngeal carcinoma. 4 patients are still alive, 1 died on postoperative
      day 6. Bilateral one-stage Crile operation with application of autograft venous
      reconstruction of the internal jugular vein is detailed. Further research in this
      field is necessary.

PMID- 8553510
TI  - [Morphological and biological features of squamous cell carcinoma of the larynx].
AB  - The study of morphological and biological criteria of laryngeal squamous cell
      carcinoma in 81 patients proved essential in the disease prognosis. In grade I
      malignancy 90 +/- 6.7% of patients were 3 years free of recurrences and
      metastases, in grade 11 - 76 +/- 8.6%, in grade III - 50 +/- 15.8%. Aneuploid
      laryngeal tumors produced recurrences 6 times more frequently than diploid ones.
      3-year recurrence--and metastases-free survival was reported in 88.7 +/- 6.3% of
      patients with diploid and 59.3 +/- 7.7%. 7% with aneuploid tumors (p < 0.05).

PMID- 8553511
TI  - [Organ pathology in Wegener's granulomatosis].
AB  - The author examines changes observed in the upper respiratory tract and the ear
      in WG permitting its differentiation from atrophic rhinitis, ozena, malignant
      reticulosis, mycosis, etc. In acute WG one can often find acute otitis media
      complicated by facial nerve paresis. In chronic WG adhesive otitis and
      neurosensory hypoacusis occur more frequently.

PMID- 8553512
TI  - [Main principles of functional intranasal surgery of paranasal sinuses].
AB  - The analysis of complications consequent to 200 endoscopic intranasal operations
      (computed tomography was performed preoperatively in 96 and was not performed in
      104 patients) has shown that the incidence of serious complications in both
      groups was minimal and that of such complications as eyelid hematoma, neuralgia
      and hemorrhage was similar. Complication-safe operative procedure is described.
      It is believed that the absence of computed tomograms should not cause the change
      of functional intranasal surgery for radical surgery by external approach or
      common polypectomy.

PMID- 8553513
TI  - [Possibilities of the use of the sinus catheter IaMIK in rhinology].
AB  - Multifunctional sinus-catheter [symbol: see text] is a helpful modality in
      investigation of affected nasal cavity and paranasal sinuses. It can be used to
      obtain wash-offs from nasal and paranasal mucosa, contrast image of unilateral
      paranasal sinuses, to prepare for operations, to treat acute and chronic nasal
      and paranasal conditions, to stop nasal hemorrhage, to take expertise and
      prognosis of nasal outlet openings patency.

PMID- 8553514
TI  - [Present-day aspects of tonsillar problems].
AB  - The analysis of 1247 case histories of chronic tonsillitis and peritonsillar
      abscesses of tonsillogenic origin has shown that annual number of tonsillectomies
      for chronic tonsillitis is decreasing while the number of patients with
      peritonsillar abscesses is going up. The tendency is explained by several
      factors, among them overestimation of the efficacy reached with conservative
      therapy of chronic tonsillitis. The authors promote wider use of tonsillectomy as
      an effective preventive tool for peritonsillar abscesses. The latter should be
      more frequently managed with abscess tonsillectomy.

PMID- 8553515
TI  - [Clinical features of spastic dysphonia].
AB  - Clinical, neurological, endoscopic, psychological findings, questionnaire data on
      vegetative sphere, diaphragm x-ray, articulation test and Viene test system
      evidence obtained on 25 patients with phonic spasm confirm organic neurological
      nature of spastic dysphonia as focal muscular dystonia. This condition can be
      accompanied with tremor, rotatory, winking and writers' spasms, oromandibular
      dystonia. As indicated by positive treatment outcomes, combined treatment of
      phonic spasm with GABA-ergic drugs of clonazepam (antelepsin) and baclofen,
      orthophonic voice correction, physiotherapy is pathogenetically justified.

PMID- 8553516
TI  - [Treatment of gunshot wounds of the ear].
AB  - Of 20 males and 2 females aged 18-40 wounded in the ear region and admitted to
      ENT hospitals, 68% had fragmentation effects, 32% gun wounds, 83% combined
      injuries. Damage to the temporal bone took place in 66.5%. Foreign body (bullet
      or fragment) was present in half of the cases. Facial paralysis, unilateral
      deafness have developed in 40% and 2/3 of the victims, respectively. Advanced
      otiatric and neurological methods warranted removal of the foreign bodies in all
      the cases, filling of temporal bone defects with island neurovascular flap from
      the musculus nutans and musculus temporalis. Lethal outcome due to
      meningoencephalitis occurred in one case only.

PMID- 8553517
TI  - [Features of rhinologic and otoneurologic symptoms and complications in
      intracranial tumors growing into the nose and paranasal sinuses].
AB  - The authors analyse rhinological and otoneurological symptoms in 50 patients with
      benign craniofacial tumors verified at surgical interventions, computed
      tomography, NMR-tomography. The tumors involved anterior parts of the brain stem,
      nasal cavity and paranasal sinuses, 34 tumors were diagnosed as meningiomas.
      Clinical correlations with tumor histology and topography were noted. Specific
      ENT preoperative, postoperative and long-term complications are described. The
      diagnosis and treatment of the above patients need cooperation with specialists
      of the allied fields: neurosurgeons, neuroroentgenologists, otoneurologists,
      neuro-ophthalmologists.

PMID- 8553518
TI  - [2 cases of follicular and radicular (basic) maxillary cysts with significant
      destruction of bone walls].

PMID- 8553520
TI  - Practical applications of IAH research.

PMID- 8553519
TI  - [Test control in the evaluation of knowledge in otorhinolaryngology].

PMID- 8553521
TI  - International disease surveillance: January to March 1995.

PMID- 8553522
TI  - Development of a diagnostic approach to the identification of rabbit haemorrhagic
      disease.
AB  - Haemagglutination and ELISA tests, and negative contrast electron microscopy,
      have been used to identify rabbit haemorrhagic disease virus in naturally
      occurring cases of the disease and in experimentally infected rabbits in the
      United Kingdom. Haemagglutination tests alone are not satisfactory for the
      diagnosis because non-haemagglutinating isolates of the virus, otherwise
      indistinguishable from others, have been found in some outbreaks.
      Haemagglutination inhibition tests have shown that a proportion of both
      commercial laboratory and wild rabbits in the UK are seropositive to the virus
      although they have not been associated with clinical disease. This observation,
      made previously in other parts of Europe, may indicate the longstanding
      circulation of a related but non-pathogenic strain of virus. Naturally occurring
      antibody appears to afford a high degree of protection against experimental
      challenge with virulent virus.

PMID- 8553523
TI  - Use of ACTH stimulation tests to monitor the treatment of canine
      hyperadrenocorticism.
AB  - The case histories of 60 dogs with hyperadrenocorticism were reviewed. Fifty-four
      of the dogs were treated with mitotane at a mean daily dose rate of 48.8 mg/kg
      (range 25.6 to 84 mg/kg) for between four and 21 days. The mean weekly
      maintenance dose of mitotane was 48.8 mg/kg. An adrenocorticotrophic hormone
      (ACTH) stimulation test was performed before the treatment began, and in 30 cases
      at the end of the induction course, and the response to ACTH was measured at
      regular intervals thereafter. Nine of the treated dogs developed complete
      hypoadrenocorticism during treatment and required permanent mineralocorticoid
      replacement therapy. Twelve of the dogs had normal responses to an ACTH
      stimulation test before treatment, and the diagnosis of hyperadrenocorticism was
      based on the result of a low-dose dexamethasone suppression test. These 12 dogs
      had consistently lower cortisol levels before and after stimulation with ACTH and
      four of them developed complete hypoadrenocorticism. In general the clinical
      signs were well controlled when the cortisol levels were less than 105 nmol/litre
      before and after the stimulation test. Dogs in which the clinical signs recurred
      had cortisol levels between 210 and 580 nmol/litre after the test, a level which
      is within the normal pretreatment range. Twenty-seven of the treated dogs died
      and six of these deaths were attributable directly to the disease or therapy. The
      median survival time of the 54 treated dogs was 30 months; eight dogs died during
      the first 16 weeks of treatment, and the dogs which survived this period had a
      median survival time of 39 months (mean 50 months).

PMID- 8553524
TI  - Serum prolactin concentration in pseudopregnant and normally reproducing goats.
AB  - Previous experiments with bromocriptine suggested that prolactin plays a role in
      the aetiology of pseudopregnancy in goats. Serum prolactin concentration was
      measured in a herd of white Dutch dairy (Saanen) goats when hydrometra (a typical
      characteristic of pseudopregnancy) was diagnosed by ultrasound, during the
      spontaneous development of pseudopregnancy, and in normally reproducing goats
      during the breeding season. In the normally reproducing does the prolactin
      concentration decreased at the beginning of the breeding season. In 12 of 14
      pseudopregnant goats the prolactin concentration was within the range observed in
      the normally reproducing goats on the day that hydrometra was diagnosed. In two
      goats the prolactin concentration was low during the first few weeks of
      pseudopregnancy and in a third it fluctuated. There was no correlation found
      between the concentration of prolactin and the development or the presence of a
      persistent corpus luteum. These results suggest that prolactin does not play a
      crucial role in the aetiology of pseudopregnancy in the goat.

PMID- 8553525
TI  - Canine atopic disease: therapeutic use of an evening primrose oil and fish oil
      combination.

PMID- 8553526
TI  - Cyclosporin-responsive keratoconjunctivitis in the cat and horse.

PMID- 8553527
TI  - Bioavailability of different benzimidazole volume-dose formulations in sheep.

PMID- 8553528
TI  - Serum protein concentrations in clinical cases of ovine paratuberculosis (Johne's
      disease).

PMID- 8553529
TI  - 'Stupid calves'.

PMID- 8553530
TI  - Locums--a concession for the veterinary profession.

PMID- 8553531
TI  - Possible immune deficiency in Fell ponies.

PMID- 8553532
TI  - Computer modeling of prototypic and aberrant nucleocapsids of varicella-zoster
      virus.

PMID- 8553533
TI  - Virus and host-specific adaptations in the BL1 and BR1 genes of bipartite
      geminiviruses.
AB  - The host range of individual geminiviruses may be quite narrow, and closely
      related viruses can exhibit distinct host adaptations. Two such bipartite
      geminiviruses are bean golden mosaic virus (GBMV) and tomato golden mosaic virus
      (TGMV). In both, the BL1 and BR1 genes are required for the spread of virus
      infection in plants. We have investigated the contributions of BL1 and BR1 to
      host-specific phenotypes of BGMV and TGMV by constructing hybrid viruses in which
      these coding regions were exchanged. Hybrids were assayed on bean, a good host
      for BGMV, and Nicotiana benthamiana, a good host for TGMV. A BGMV hybrid having
      TGMV BL1 and BR1 efficiently infected beans, but elicited attenuated symptoms. In
      N. benthamiana, this hybrid had slightly increased virulence and DNA accumulation
      relative to wild-type BGMV. A TGMV hybrid having BGMV BL1 and BR1 was virulent in
      N. benthamiana, but elicited attenuated symptoms. However, this hybrid exhibited
      no gain of function in beans relative to wild-type TGMV. Hybrid viruses with TGMV
      BL1 and BGMV BR1 had severely defective phenotypes in either viral or host
      background. Although exchanging BL1 and BR1 between BGMV and TGMV did not change
      host range, some host adaptation of these genes is suggested. However, virus
      specific compatibility between BL1 and BR1 is of more importance for viability.
      Thus, these gene products may act in concert to potentiate virus movement.

PMID- 8553534
TI  - Tropism of bunyaviruses: evidence for a G1 glycoprotein-mediated entry pathway
      common to the California serogroup.
AB  - The California serogroup is composed of antigenically and biologically related
      viruses within the Bunyavirus genus of the Bunyaviridae. We used a large panel of
      murine cells to study their tissue tropisms and found virtually identical
      patterns of viral replication among all of the members of this serogroup, in
      contrast to other members of the family (Bunyamwera, Cache Valley, and Punta Toro
      viruses). By analyzing the nonpermissive infections with both an RNA dot-blot and
      a virus binding assay, we determined that tropism for cultured cells was
      determined at the level of entry. A truncated soluble form of the La Crosse G1
      glycoprotein (sG1) was expressed in a baculovirus system and, despite slight
      differences in glycosylation, was shown to resemble native G1 by
      immunoprecipitation with six monoclonal antibodies. sG1 bound to permissive but
      not to nonpermissive cell lines, as demonstrated by flow cytometry. The sG1
      effectively blocked infection of permissive cell lines with all of the California
      serogroup viruses, but did not block infection of two other bunyaviruses. These
      results indicate that the California serogroup bunyaviruses share a common
      receptor on vertebrate cells which may differ from the receptor used by other
      Bunyaviridae and demonstrate that the G1 glycoprotein is the virus attachment
      protein. sG1 will be a useful reagent in the search for a putative receptor
      molecule.

PMID- 8553535
TI  - Human papillomavirus type 16 capsid proteins produced from recombinant Semliki
      Forest virus assemble into virus-like particles.
AB  - Several neutralizing sites of the human papillomavirus (HPV) capsid are known to
      be critically dependent on the conformation of the capsid. However, efficient
      production of HPV16 capsids in mammalian cells has been difficult, possibly
      because the HPV genome contains negative regulatory elements. To circumvent these
      problems, we cloned the HPV16 L1 and L2 genes from a healthy HPV16-infected woman
      into a Semliki Forest virus based expression vector (P. Liljestrom and H. Garoff,
      Biotechnology 9, 1356-1361, 1991). Recombinant HPV16 L1- or L2-producing Semliki
      Forest virus was generated and used for infection of mammalian cells. The HPV16
      L1 and L2 proteins were efficiently expressed and the majority of the L1 protein
      self assembled into virus-like particles (VLPs). Coexpression of L1 and L2
      resulted in incorporation of L2 into the VLPs. The particles had a density of
      approximately 1.3 g/ml as determined by density gradient centrifugation.
      Transmission electron microscopy revealed that the particles had a morphology
      similar to native virions. The HPV16 VLPs produced by the Semliki Forest virus
      expression system may be useful as a conformationally correctly assembled target
      for studies of HPV attachment, assembly, serology, or vaccination.

PMID- 8553536
TI  - The adeno-associated virus Rep78 protein is covalently linked to viral DNA in a
      preformed virion.
AB  - Resolution of the covalently closed terminus of adeno-associated Virus (AAV) DNA
      is mediated by viral replication protein Rep78 or Rep68. In vitro studies with
      purified Rep proteins indicate that concurrent with this resolution is a covalent
      attachment of one of the proteins to the 5' end of the viral genome. The in vivo
      existence and fate of the covalently associated Rep protein during the virus life
      cycle has not yet been elucidated. In this report, we use immunoprecipitation
      analyses to demonstrate that the Rep78 protein is covalently attached to viral
      DNA in a preformed virion. The attached Rep78 is susceptible to antibody binding
      and protease digestion, and the DNA linkage is susceptible to nuclease digestion,
      therefore Rep78 is probably located on the outside of the particle. Rep proteins
      are also attached to double-stranded replicative-form monomer (RFM) DNA in
      extracts from AAV and adenovirus coinfected cells. Rep protein attachment to RFM
      and encapsidated AAV DNA suggest that the covalent complex is an intermediate in
      virus assembly. These observations are similar to those noted by others for the
      autonomous parvoviruses and provide additional insights into parvovirus assembly.

PMID- 8553537
TI  - HNF3 binds and activates the second enhancer, ENII, of hepatitis B virus.
AB  - The basic functional unit of hepatitus B virus (HBV) enhancer II (ENII) is
      located within nt 1687-1774, which is defined as the B fragment in our previous
      papers. A major trans-acting factor binding site has been identified within the B
      fragment. The sequence corresponding to this binding site was named B2. In this
      paper, several point mutations were introduced into the B2 subunit by PCR
      mediated site-directed mutagenesis. CAT analysis indicated that the TGTTTGTTT
      motif within the B2 subunit was critical for the activity of ENII. Mutations of
      individual nucleotides within this motif could decrease the activity of ENII.
      Electrophoresis mobility shift assay revealed that the liver-enriched
      transcription factors hepatocyte nuclear factor (HNF) 3 alpha and HNF3 beta bound
      to the B2 subunit specifically and the TGTTTGTTT motif was essential for DNA
      protein interaction. Anti-HNF3 alpha and anti-HNF3 beta antisera could block such
      binding ability. Moreover, HNF3 beta could switch on the activity of ENII in HeLa
      cells and the activity of ENII could be suppressed by antisense HNF3 alpha and
      antisense HNF3 beta mRNA in HepG2 cells. These results prompted the conclusion
      that HNF3 was crucial for the liver-specific activity of ENII, which in turn
      contributed significantly to the liver specificity of HBV.

PMID- 8553538
TI  - Interferon treatment inhibits virus replication in HIV-1- and SIV-infected CD4+ T
      cell lines by distinct mechanisms: evidence for decreased stability and aberrant
      processing of HIV-1 proteins.
AB  - We have examined the effects of interferon (IFN)-alpha/beta on HIV-1 and SIV
      replication in CD4+ T-cell lines. To enable us to examine these effects on a
      single cycle of virus replication, cells were synchronously infected with HIV-1
      LAI or SIV mac251. Cell lines included MT4 cells which were responsive to IFN
      and, as controls, C8166 cells which failed to respond to interferon treatment.
      Similar to previous reports, we found that replication of both HIV-1 and SIV was
      markedly inhibited in responsive MT4 cell lines treated with IFN. No such
      decreases were observed in HIV-1-infected, IFN-treated C8166 cells. Levels of
      both intracellular and extracellular viral antigens decreased in both HIV-1- and
      SIV-infected MT4 cells treated with IFN. Whereas steady state levels of viral
      specific RNAs dramatically declined in SIV-infected cells, no such decrease was
      observed in IFN-treated HIV-1-infected cells. In accordance with these data, the
      rate of viral protein synthesis did not significantly change in HIV-1-infected,
      IFN-treated MT-4 cells. Western blot analysis of extracts prepared from IFN
      treated HIV-1-infected cells revealed a decreased accumulation of most HIV-1
      specific glycoproteins and proteins with the exception of the pr55 gag precursor.
      Pulse-chase experiments confirmed the enhanced stability of pr55 in IFN-treated
      cells, but also unexpectedly demonstrated the accelerated and quantitative
      processing of the p26 precursor (p24 capsid [CA] plus p2) to the final processed
      p24 (CA) polypeptide. These data, taken together, suggest that IFN deregulated
      viral protein processing and caused reduced protein stability in HIV-1-infected
      cells while inhibiting an earlier stage of replication in SIV-infected cells.

PMID- 8553539
TI  - Effector functions of antibody and CD8+ cells in resolution of rotavirus
      infection and protection against reinfection in mice.
AB  - The importance of antibody and CD8+ cells in resolution of murine rotavirus
      (EDIM) infection and protection against reinfection was examined with two strains
      of B-cell-deficient mice. Following inoculation of one strain (JHD), rotavirus
      infection was resolved within days, but when later reinoculated with EDIM, these
      mice again shed rotavirus. Thus, effector mechanisms other than antibody resolved
      viral shedding in JHD mice but were insufficient to prevent reinfection. EDIM
      shedding in another B-cell-deficient mouse strain (microMT) diminished but was
      not fully resolved 93 days after the initial infection, thus demonstrating that
      antibody could also be important in resolution of rotavirus infection. When
      depleted of CD8+ cells by monoclonal antibody treatment before EDIM inoculation,
      JHD mice were unable to resolve shedding. Even though microMT mice did not fully
      resolve their initial infection, depletion of CD8+ cells 49 days after initial
      inoculation resulted in a burst of shedding. Thus, CD8+ cells were involved in
      resolution of the initial EDIM infection in both strains of B-cell-deficient
      mice. Finally, when microMT mice were depleted of CD8+ cells before the initial
      EDIM infection, gradual resolution of rotavirus shedding was still observed,
      suggesting a third effector mechanism was also involved in resolution of
      rotavirus infection in mice.

PMID- 8553541
TI  - Large deletions in the genome of Chlorella virus CVK1.
AB  - Large (30-45 kbp) deletions were induced in the Chlorella virus CVK1 genome by UV
      irradiation. Restriction endonuclease maps of the mutant genomes showed that
      these deletions occurred in a region located from 1.5 kbp to 47 kbp from the left
      DNA end. The nucleotide sequences determined around the deletion boundaries
      indicate that the deletion process took place by both homologous and
      nonhomologous recombinations. In one case, the recombination site was within a
      region of about 600 bp, consisting of 40 tandem repetitions of a 15-bp sequence
      element. The deleted region may contain several multigene families. Northern blot
      analyses with probes including the genes for translational elongation factor 3
      and DNA polymerase showed no discernible aberrancy in the gene expression
      patterns in the mutants. However, at least two protein bands were missing from
      the mutant virions.

PMID- 8553540
TI  - Immune effector mechanisms required for protection to rabies virus.
AB  - Genetically engineered mice with targeted mutations in genes encoding
      immunologically relevant molecules were used to elucidate the role of different
      immune effector mechanisms in protection against a rabies virus (RV) infection.
      In vaccinated animals challenged with a highly virulent strain of RV, antibodies
      were crucial in protection. In naive mice challenged with an attenuated strain of
      the virus that does not cause disease in adult fully immunocompetent mice but
      kills RAG mice that lack functionally active T and B cells, different immune
      effector mechanisms were shown to suffice for protection.

PMID- 8553542
TI  - Large deletions in antigenic variants of the chlorella virus PBCV-1.
AB  - Four spontaneously derived, antigenic variants of chlorella virus PBCV-1
      contained 27- to 37-kb deletions in the left end of the 330-kb genome. Two of the
      mutants, which were serologically identical, had deletions that began from map
      position 4.9 or 16 and ended at position 42.2 kb. In total, the two deleted
      regions encoded 28 putative functional open reading frames (ORFs); these
      deletions probably arose from homologous recombination. The other two mutants,
      which were serologically identical but distinct from the first two mutants,
      lacked the entire left terminal 37 kb of the PBCV-1 genome, including an
      identical 2.2-kb inverted terminal repeat region present at both ends of the wild
      type genome. The deleted left end region was replaced by the transposition of an
      inverted 7.7- or 18.5-kb copy of the right end of the PBCV-1 genome. The region
      deleted in these two viruses encoded 26 single-copy ORFs, of which 23 were common
      to those deleted in the first two mutant viruses. The junctions of the
      deletions/transpositions probably arose from nonhomologous recombination. Taken
      together, the results indicate that 40.1 kb of single-copy DNA encoding 31 ORFs
      at the left end of the genome are unnecessary for PBCV-1 replication in Chlorella
      strain NC64A in the laboratory. The results also indicate that the size of the
      inverted terminal repeat region in this virus can be highly variable and that the
      PBCV-1 DNA packaging process tolerates large changes in genome size.

PMID- 8553543
TI  - GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 and
      vaccinia virus polymerases.
AB  - The glycoprotein gene of Ebola virus contains a translational stop codon in the
      middle, thus preventing synthesis of full-length glycoprotein. Twenty percent of
      the mRNA isolated from Ebola virus-infected cells was shown to be edited,
      containing one additional nontemplate A in a stretch of seven consecutive A
      residues. Only the edited mRNA species encoded full-length glycoprotein, whereas
      the exact copies of the viral template coded for a smaller secreted glycoprotein.
      Expression of the glycoprotein by an in vitro transcription/translation system,
      by the vaccinia virus/T7 polymerase system, and by recombinant vaccinia virus
      revealed that full-length glycoprotein was synthesized not only when the edited
      glycoprotein gene (8A's) was used as a template for T7 and vaccinia virus
      polymerases, but also when the nonedited (genomic) glycoprotein gene was used.
      Analysis of mRNA produced by T7 and vaccinia virus polymerase from the 7A's
      construct revealed that 1-5% contained alterations at the same site that was also
      edited by the Ebola virus polymerase. Our data indicate that the editing site in
      the Ebola virus glycoprotein gene is recognized not only by Ebola virus
      polymerase but also by DNA-dependent RNA polymerases of different origin.

PMID- 8553544
TI  - Genetic determinants of feline leukemia virus-induced multicentric lymphomas.
AB  - Three discrete forms of feline leukemia virus (FeLV)-associated lymphoma have
      been described clinically: (1) thymic, (2) alimentary, and (3) multicentric. The
      most common and best-characterized lymphomas are of T-cell origin, generally
      occurring in the thymus. These tumors typically contain mature T-cells, involve
      the activation of a distinctive set of proto-oncogenes, and contain FeLV
      proviruses whose long terminal repeat (LTR) sequences contain tandemly repeated
      enhancers. Previous studies of a small group of extrathymic, multicentric
      lymphomas implicated a different set of genetic determinants. The present study
      expands those observations by examining the lineage of origin, the involvement of
      proto-oncogenes, and the structure of LTR and env gene sequences in a set of 11
      natural, extrathymic lymphomas of the multicentric type. A pattern of genetic
      events associated with FeLV-positive multicentric lymphomas emerges from this
      analysis that is clearly distinct from the pattern associated with thymic
      lymphomas. The tumors do not contain T-cells or B-cells, as evidenced by the germ
      line organization of TCR beta and IgH loci. Proto-oncogenes strongly implicated
      in T-cell lymphomagenesis are not involved in these tumors. Rather, a distinct
      set of proto-oncogenes may be involved. Most striking is the repeated occurrence
      of an FeLV isolate whose LTR and env gene bear unique sequence elements.

PMID- 8553545
TI  - Avian sarcoma leukemia virus protease linked to the adjacent Gag polyprotein is
      enzymatically active.
AB  - The activity of avian sarcoma leukemia virus (ASLV) protease (PR) prior to its
      release from the precursor protein was determined by introducing mutations at the
      cleavage site between PR and the adjacent upstream nucleocapsid (NC) protein. Gag
      DNA fragments containing these mutations were cloned into expression vectors and
      introduced into Escherichia coli in which the ASLV proteins were expressed. The
      dipeptide NC-PR containing these mutations did not undergo autoprocessing when
      expressed in bacterial cells and the fused proteins were devoid of enzymatic
      activity. However, when the whole Gag polyprotein containing these mutations was
      expressed in bacterial cells, other PR cleavage sites in the viral Gag
      polyprotein underwent normal cleavage, indicating that the release of free PR is
      not a prerequisite for correct processing of the ASLV Gag precursor.

PMID- 8553546
TI  - Influenza A virus-specific H-2d restricted cross-reactive cytotoxic T lymphocyte
      epitope(s) detected in the hemagglutinin HA2 subunit of A/Udorn/72.
AB  - BALB/c mice immunized with a vaccinia virus recombinant expressing the influenza
      A virus (A/Udorn/72; subtype H3) hemagglutinin HA2 (H3HA2) induced a strong CD8+
      cytotoxic T lymphocyte (CTL) response which was H-2d-restricted. Two peptides,
      derived from the primary sequence of the H3HA2 and consistent with the predictive
      motif for Kd-restricted epitopes, were tested for their ability to be presented
      to the CTLs by P815 cells. Peptides corresponding to the amino acids
      93SYNAELLVAL102 and 181GYKDWILWI189 of the HA2 primary sequence sensitized target
      cells for lysis by the HA2-specific CTLs. Secondary in vitro stimulation with
      dendritic cells as a source of antigen presenting cells treated with peptide 93
      102, or infected with recombinant vaccinia virus (HA2-VACC), induced type A cross
      reactive CTLs from A/Udorn/72 immune spleen cells. This CD8+ CTL epitope overlaps
      with an H3HA2 I-Ad-restricted T helper epitope 96-104 recently reported by
      others. The H3HA2 epitope described here is the first CTL epitope in the
      influenza hemagglutinin which is found in all three subtypes of influenza A
      virus.

PMID- 8553547
TI  - Mutational analysis of the murine coronavirus spike protein: effect on cell-to
      cell fusion.
AB  - The spike (S) protein of murine coronavirus strain A59 (MHV-A59) is a type I
      membrane protein that induces membrane fusion. In this study we have analyzed the
      role of two domains in the S protein on fusion. The 180-kDa mature S protein is
      partially cleaved into two 90-kDa subunits during transport to the plasma
      membrane. We have identified several amino acids that are important for cleavage
      of S, and we show that cleavage is not strictly required for fusion. However, the
      level of cleavage seems to influence the fusion kinetics. After introduction of
      an arginine at position P2 to mimick the MHV-JHM cleavage site, full cleavage of
      the spike protein was obtained. Further, we analyzed the effect of mutations in
      the transmembrane (TM) domain of the S protein. Maturation and cell surface
      expression of the mutant proteins were not affected, and all proteins became
      acylated. The mutant in which the predicted transmembrane domain was shortened
      did not induce syncytia. From a group of mutants in which several conserved
      cysteines in the TM domain had been replaced by serines, one was unable to induce
      syncytia, another showed delayed syncytia formation, and the third mutant induced
      syncytia as did the wild-type protein. The potential role of the transmembrane
      domain in fusion is discussed.

PMID- 8553548
TI  - Coding changes in the 3a cell-to-cell movement gene can extend the host range of
      brome mosaic virus systemic infection.
AB  - The M1 and M2 strains of brome mosaic virus (BMV) both systemically infect the
      monocot host barley, but only the M2 strain systemically infects the dicot cowpea
      line TVu-612. We have shown previously that this difference in host range maps
      primarily to RNA3. To further characterize the role of RNA3 in host specificity,
      a series of RNA3 hybrids were tested, in inoculations with M1 RNA1 and RNA2, for
      ability to systemically infect TVu-612 cowpea. Although all hybrids were
      amplified well in cowpea protoplasts and all supported systemic infection in
      barley plants, only those with the 3a cell-to-cell movement gene of BMV-M2
      supported systemic infection of cowpea. The sequences of the M1 and M2 3a
      proteins differ at four positions. Introducing these four coding differences
      individually or in various combinations into M1 RNA3 revealed that all four
      influenced BMV adaptation to cowpea and that these four differences were
      sufficient to account for the difference in ability between M1 and M2 RNA3s to
      support systemic infection of this legume. These coding changes were also
      associated with faster spread of infection in inoculated cowpea leaves,
      suggesting that they influence the ability to systemically infect TVu-612 cowpea
      through effects on the rate of cell-to-cell spread.

PMID- 8553549
TI  - Generation and characterization of an influenza virus neuraminidase variant with
      decreased sensitivity to the neuraminidase-specific inhibitor 4-guanidino
      Neu5Ac2en.
AB  - A variant of the influenza virus NWS/G70C has been generated which has decreased
      sensitivity in vitro to the neuraminidase-specific inhibitor, 4-guanidino
      Neu5Ac2en. The virus is 1000-fold less sensitive to the 4-guanidino-Neu5Ac2en in
      a plaque assay, but only 10-fold less sensitive to 4-amino-Neu5Ac2en. In an
      enzyme inhibition assay 250-fold more drug was needed to achieve inhibition
      comparable to that observed with the parent virus. In contrast to the plaque
      assay, the virus was fully sensitive to 4-amino-Neu5Ac2en in the enzyme
      inhibition assay. Kinetic analysis of 4-guanidino-Neu5Ac2en binding demonstrated
      that the variant no longer exhibited the slow binding characteristic seen with
      the parent and other influenza viruses and inhibition by Neu5Ac2en was also
      decreased. However, binding to 4-amino-Neu5Ac2en remained the same as the parent.
      Sequence analysis of this virus revealed a mutation at a previously conserved
      site in the enzyme active site of the neuraminidase, Glu 119 to Gly.
      Crystallographic analysis of the mutant neuraminidase with and without bound
      inhibitor confirmed this mutation and suggested that the reduced affinity for the
      4-guanidino-Neu5Ac2en derives partly from the loss of a stabilizing interaction
      between the guanidino moiety and the carboxylate at residue 119, and partly from
      alterations to the solvent structure of the active site.

PMID- 8553550
TI  - The nonstructural NSm protein of tomato spotted wilt virus induces tubular
      structures in plant and insect cells.
AB  - The expression and subcellular location of the 33.6-kDa nonstructural protein NSm
      of tomato spotted wilt virus (TSWV) was analyzed in Nicotiana rustica plants and
      protoplasts as a function of time. Immunofluorescent studies in protoplasts
      isolated from TSWV-infected N. rustica leaves showed that this protein could
      first be detected close to the periphery of the cell, near the plasmamembrane,
      and later in tubular structures emerging from the cell surface. In situ, these
      tubules appeared specifically in the plasmodesmata, suggesting their involvement
      in cell-to-cell movement of the virus during systemic infection. In protoplasts
      transfected with an expression vector containing the NSm gene, similar tubules
      were formed, indicating that NSm has the ability to form these structures in the
      absence of other virus-specific components. To test whether plant-specific
      components were involved in tubule formation, the NSm gene was also expressed in
      a heterologous expression system, i.e., insect cells. Spodoptera frugiperda and
      Trichoplusia ni cells were infected with a recombinant baculovirus expressing the
      NSm-gene (AcNPV/NSm). The efficient formation of NSm-containing tubules emerging
      from the surface of both cell types indicate that no plant-specific cell
      structures or proteins are involved in their development.

PMID- 8553551
TI  - Involvement of spicules in the formation of vaccinia virus envelopes elucidated
      by a conditional lethal mutant.
AB  - The envelope of immature vaccinia virions consists of a lipoprotein bilayer upon
      which a precise curvature is imposed by acquisition of an external scaffold of
      spicules. Self-assembly of this tegument was examined employing our ts 6757
      mutant, which induces accumulation of immature envelopes at the restrictive
      temperature. With ts 6757 the envelope bilayers were also assembled into an
      alternative membrane configuration in the form of flexible cylinders or tubes of
      uniform width, lacking the spicule coat. Such tubes became extensions of or were
      continuous with the spherical virion envelopes. The approximately 65 kDa spicule
      protein, L65, product of gene D13L on the HindIII map, generally designated as a
      late protein, was expressed as an early function in presence of hydroxyurea, an
      inhibitor which entirely blocked vaccinia DNA synthesis without stopping assembly
      of immature envelopes. Labeling of thin sections by immunogold for electron
      microscopy demonstrated that L65 is present at the surface of immature virions,
      consistent with the position of spicules on envelopes. Transiency of the spicule
      scaffold was documented by (a) absence of L65 from intracellular mature virions
      (IMV) and (b) rapid turnover of L65 during ts 6757 virus replication at the
      permissive temperature but conservation of this protein at restrictive
      temperature, as demonstrated in pulse-chase experiments. Time-related decrease in
      MW of L65 to a smaller polypeptide is interpreted as evidence suggesting that the
      spicules attached to the envelope are assembled from a higher MW precursor.

PMID- 8553552
TI  - Organization of the vaccinia envelope and relationship to the structure of
      intracellular mature virions.
AB  - Protrusions covering the surface of intracellular mature virions (IMV), termed by
      us surface tubular elements (STE), are released in a quasi-intact form during
      stripping of the envelope. The concentrated, reproducibly isolable STE were shown
      to contain the 58-kDa 4c polypeptide and prominent protein antigens residing at
      the surface of IMV. The major core protein 4b, identified as a minor contaminant
      of STE, presumably became detached along with STE during the shearing off
      process. Antibodies against protein 4b became specifically bound to the surface
      of isolated cores, where a palisade layer of rodlets occurs. The same antibodies
      absorbed onto isolated STE where similar rodlets were evident. Based on the new
      observations we constructed a model of the organization of the IMV envelope and
      its relationship to the core.

PMID- 8553553
TI  - Role of glucocorticoid receptor binding sites in the human immunodeficiency virus
      type 1 long terminal repeat in steroid-mediated suppression of HIV gene
      expression.
AB  - Dexamethasone inhibited human immunodeficiency virus type 1 (HIV-1) long terminal
      repeat (LTR)-directed gene expression in cells of T and B lymphoblastoid
      lineages, but not in monocytic cells. Suppression required an intact
      glucocorticoid receptor (GR), as it was amplified by transfection of lymphocytes
      with a plasmid encoding the human GR and blocked by the receptor antagonist
      RU486. These results were in direct contrast to the effects of dexamethasone on a
      murine leukemia retrovirus promoter where, consistent with the findings of
      others, activation of gene expression was obtained. Potential regions of the HIV
      1 LTR mediating these effects were sought, with sequence homologies predicting
      two new glucocorticoid response element half-sites, GRE-II (nucleotides -6 to -1)
      and GRE-III (+ 15 to + 20), downstream from a previously identified GR DNA
      binding domain, GRE-I (-264 to -259). Mutational analyses documented the loss of
      inhibitory activity attendant on changes in GRE-III and the independence of
      steroid-mediated effects from GRE-I and GRE-II. Consistent with these findings,
      electrophoretic mobility shift assays revealed a difference in binding of
      cellular factors to GRE-III in cells of T and B lymphocyte vs. monocytic
      lineages. Binding sites for the cellular transcription factor leader binding
      protein (LBP-1) were found to overlap with GRE-III, and LBP-1 interacted with
      this element in the HIV LTR only in T and B lymphocytic extracts. We hypothesize
      that GRE-III sequence-specific effects, including modulation of LBP-GR
      interactions, underlie the negative regulatory effect of glucocorticoids on HIV-1
      gene expression, with some specificity for cell type.

PMID- 8553554
TI  - Polymerase activity of in vitro mutated rabies virus L protein.
AB  - The large (L) protein of nonsegmented negative-strand RNA viruses is the
      multifunctional catalytic component of the viral ribonucleoprotein (RNP) complex.
      To address the role of conserved rabies virus (RV) L protein sequences predicted
      to be involved in RNA polymerase activity, a reverse genetics approach was
      applied that allows intracellular reconstitution of transcriptionally active RV
      RNPs from plasmid-encoded proteins. Artificial RV model genomes encoding
      bacterial chloramphenicol acetyltransferase or firefly luciferase was used to
      determine the polymerase activity of a series of 23 RV L proteins mutated in the
      highly conserved C motif of the proposed polymerase module. All constructs with
      mutations of the GDN core sequence of motif C, which is proposed to be a variant
      of the catalytical XDD residues of RNA polymerase and reverse transcriptases,
      failed to express the reporter genes. In addition, the identity of the upstream
      residues AQ was crucial for maintenance of polymerase activity. Several
      conservative and nonconservative mutations introduced into the three amino acids
      QVL located downstream of the GDN core resulted in reduced polymerase activities
      and expression of luciferase in the range 0.4 to 92% compared to the parental L
      protein.

PMID- 8553555
TI  - Identification of immunodominant regions and linear B cell epitopes of the gE
      envelope protein of varicella-zoster virus.
AB  - The envelope proteins of varicella-zoster virus (VZV) are highly immunogenic and
      one of the most abundant is glycoprotein E (gE). However, its immunodominant
      regions and epitopes have not been identified. In this study, using human sera
      from individuals with recent varicella or zoster infections, we have localized
      antigenic sequences of gE using recombinant hybrid Ty-virus-like particles (VLPs)
      carrying overlapping fragments of the gE protein. gE(1-134)-VLPs (particles
      carrying amino acids 1-134 of gE) and, to a lesser extent, gE(101-161)-VLPs were
      found to be the most antigenic when tested by Western blotting and ELISA. Other
      fragments of gE (spanning residues 161-623) showed weak or no antigenicity.
      Pepscan analysis of human sera on overlapping synthetic peptides representing
      residues 1-135 of gE revealed that the most antigenic region was between residues
      50 and 135. Three immunodominant sequences (residues 86-105, 116-135, and, to a
      lesser extent, 56-75) were detected using sera from both varicella and zoster
      patients. All sera from varicella, but not zoster, patients reacted strongly with
      an epitope in peptide 66-85. Other epitopes were recognized weakly by some
      varicella or zoster sera. More sera need to be tested to assess the potential
      disease specificity of these epitopes. The neutralizing monoclonal antibody (MAb)
      IF-B9 reacted with residues 71-90; however, another neutralizing MAb, SG1A, which
      bound to both gE(1-134)-VLPs and gE(101-161)-VLPs did not bind to any peptide.
      The identification of immunodominant sequences of gE will help toward the
      development of a subunit VZV vaccine.

PMID- 8553556
TI  - Development of a sustainable chick cell line infected with Marek's disease virus.
AB  - Marek's disease virus (MDV) is a highly infectious and cell-associated avian
      herpesvirus. Fully productive infections with MDV are restricted to feather
      follicle epithelium of afflicted birds. In culture, MDV infection of primary
      chick (CEF) and duck embryo fibroblast cells is semiproductive. Passage of MDV
      and production of MDV vaccines is limited to these primary cell-associated
      systems. The finite life span of primary avian cell cultures has hampered efforts
      to use positive selection in generation of recombinant MDV and complicates
      studies of temporal gene regulation. In this report, we describe continuous chick
      fibroblast cell lines (MDV OU2.2 and MDV OU2.1) which support MDV replication.
      Southern blot and PCR analyses demonstrate that these cell lines harbor MDV DNA.
      Western blot analyses indicate that MDV OU2.2 cells express at least a limited
      set of viral proteins, pp38 and pp14, similar to that seen in MDV-lymphoblastoid
      cells. Presence of distinct plaques in confluent MDV OU2.2 cell monolayers is
      consistent with cytolytic semiproductive infection, similar to that observed in
      primary CEF. MDV OU2.2 cells are capable of transferring MDV infection to primary
      CEF cultures and inducing clinical signs of Marek's disease in susceptible birds.
      MDV OU2.2 cells have maintained a MDV-positive phenotype for over 16 months of
      active culture. Southern blot hybridization of MDV OU2.2 cell DNA reveals a
      distinct expansion of the MDV BamHI H fragment in a subset of viral genomes
      following long-term cultivation.

PMID- 8553557
TI  - Analysis of the leader and capsid coding regions of persistent and neurovirulent
      strains of Theiler's virus.
AB  - Most strains of Theiler's virus (TMEV) cause a persistent infection of the
      central nervous system of the mouse and a chronic demyelinating disease
      considered a model for multiple sclerosis. Two strains, on the contrary, cause an
      acute encephalitis and kill mice in a matter of days. We sequenced the leader and
      capsid coding region of three persistent (TO4, WW, and Yale) isolates and one
      neurovirulent (FA) isolate of TMEV. We compared these sequences and those already
      published for other isolates (DA, BeAn, GDVII, and Vilyuisk). The results suggest
      that virulent and persistent strains did not evolve as two separate groups, but
      rather that neurovirulent strains arose from a subgroup of persistent strains.
      The sequences of viruses isolated in different geographic areas and at different
      times were highly homologous, a surprising finding for an RNA virus. This
      suggests that severe constraints are imposed on the genome during the viral life
      cycle. The sequences of the TO4 and WW strains were identical, suggesting that
      the latter came from a laboratory contamination. The genomes of all the
      persistent strains sequenced so far contain an alternate open reading frame in
      the L region, which has been shown, in the case of the DA strain, to code for an
      18-kDa protein called "I".

PMID- 8553558
TI  - Canyon rim residues, including antigenic determinants, modulate serotype-specific
      binding of polioviruses to mutants of the poliovirus receptor.
AB  - Several mouse cell lines expressing hybrid human poliovirus receptors (hPVRs)
      bearing mutations in the first immunoglobulin-like domain were previously
      characterized for their defective binding and replication of poliovirus type 1
      Mahoney (G. Bernhardt, J. Harber, A. Zibert, M. DeCrombrugghe, and E. Wimmer,
      Virology, 203, 344-356, 1994). Here we report that these mutant hPVRs were
      utilized to explore differences in the binding behavior of the three serotypes of
      poliovirus. Type 3 polioviruses (both Sabin and the neurovirulent Leon strain)
      clearly bound to the hPVR mutant Q130G/GD, but were incapable of initiating
      infection. Also, binding at 25 degrees of poliovirus types 2 and 3 to cell lines
      expressing the hPVR mutants P84SYS/HPGA, L99GAE/AAAA, and D117F was greater than
      type 1 poliovirus. Further study of the serotype-specific interaction with mutant
      hPVRs was accomplished with antigenic hybrid viruses. Improved binding by
      antigenic hybrid viruses demonstrated that serotype-specific binding to mutant
      hPVRs is, in part, determined by the amino acid sequence of neutralization
      antigenic sites (NAgs) and the probable conformational rearrangement of amino
      acids adjacent to the NAg sites. Finally, site-directed mutants of poliovirus
      were utilized to determine the relative contributions, to hPVR interactions, of
      individual amino acids with solvent accessible side chains in the viral canyon.
      Of the 18 viable virus mutants produced, 3 (D1226A, I1089A, and VPEK1166HPGA)
      expressed impaired replication phenotypes on the mutant hPVR cell lines
      P84SYS/HYSA and D117F. A location at the rim of the poliovirus canyon was
      implicated for the interaction of the amino terminal domain of the poliovirus
      receptor with conserved and serotype-specific viral surface amino acids. The
      possible involvement of elements of neutralization antigenic sites in receptor
      binding may explain, in part, why poliovirus exists in only three serotypes.

PMID- 8553559
TI  - Structural comparison of the plant satellite viruses.
AB  - Detailed structures are now available for three plant satellite viruses,
      satellite tobacco necrosis virus (STNV), satellite tobacco mosaic virus (STMV),
      and satellite panicum mosaic virus (SPMV). It is, therefore, possible to compare
      the tertiary structure of viral protein subunits, their quaternary interactions,
      and the interactions of protein subunits with the RNA genome. This analysis
      indicates that, in spite of common function and preservation of a "jelly-roll"
      motif in the protein monomer, the three viruses are remarkably different. The
      differences include the arrangement of secondary structural elements,
      interactions of adjacent subunits, and the disposition of subunits relative to
      icosahedral symmetry axes. In each of the three viruses, however, the narrow end
      of the jelly roll forms fivefold contacts. The fivefold protein interactions are
      organized about a Ca2+ ion for STNV, an anion for STMV, and, apparently, neither
      of these for SPMV. Low-resolution neutron diffraction studies using H2O/D2O
      solvent contrast variation revealed the general location of the RNA genome within
      the STNV. In the case of SPMV, regions of electron density on the interior of the
      capsid could be assigned to RNA, although it was not possible to model the
      nucleic acid. Only for STMV was nucleic acid visible in election density maps,
      and this was manifested as double-helical RNA segments associated with each coat
      protein dimer. The observations presented here provide no support for any common
      evolutionary relationship.

PMID- 8553560
TI  - Feline leukemia virus variants in experimentally induced thymic lymphosarcomas.
AB  - This study was initiated to evaluate the in vivo infectivity and pathogenicity of
      a group of recombinant feline leukemia viruses (rFeLVs) previously generated by
      in vitro forced recombination between a FeLV subgroup A virus (FeLV-A) and an
      endogenous FeLV (enFeLV) envelope (env) element (Sheets et al., 1992, Virology
      190, 849-855). To determine infectivity of rFeLVs, neonatal cats were inoculated
      with rFeLVs alone or in combination with FeLV-A. The recombinant viruses were
      able to replicate efficiently in vivo only when administered along with FeLV-A.
      Of six co-infected cats, three developed thymic lymphosarcomas, one severe
      aplastic anemia, and two cachexia and depression; all were viremic and
      seroconverted shortly after inoculation. While both virus types were detected in
      virtually all tissues examined from these tumor-bearing cats, there was a
      particularly noteworthy sequence reversion in the rFeLVs. It is known that
      exogenous FeLV isolates carry a conserved neutralizing MGPNL epitope in the
      middle of the surface glycoprotein domain of the env gene. In contrast, the
      parental recombinant viruses used to inoculate these cats harbored the enFeLV
      derived MGPNP sequence at this position. However, all in vivo-propagated
      recombinants displayed the MGPNL sequence, while the env-encoded backbone
      flanking the MGPNL sequence was that of the parental recombinant virus. These
      results suggest that viruses with the MGPNL epitope have an in vivo proliferative
      advantage. The data also provide an explanation for the conservation of this
      epitope in exogenous FeLVs despite the existence of variant forms in enFeLV
      proviral elements with which they can recombine.

PMID- 8553561
TI  - Synthesis of bluetongue virus chimeric VP3 molecules and their interactions with
      VP7 protein to assemble into virus core-like particles.
AB  - Bluetongue virus (BTV) core-like particles (CLPs) are formed in the cytoplasm of
      insect cells when only two major proteins (VP3 and VP7) of the BTV core are
      expressed by baculovirus vectors (T. J. French and P. Roy, 1990, J. Virol. 64,
      1530-1536). We have recently reported that five small internal deletion mutants
      of VP3 form CLPs when provided with unmodified VP7 protein (D1-5; S. Tanaka and
      P. Roy, 1994, J. Virol. 68, 2795-2802). To investigate whether foreign sequences
      can be inserted into VP3 and to determine their effect on CLP formation, three of
      these internal regions (D1, D2, and D5), as well as the carboxy terminus, were
      modified to create unique restriction enzyme sites, thereby replacing VP3 coding
      regions with shorter synthetic sequences. Each modified VP3 gene was used to
      generate baculovirus expression vectors (D1I, D2I, D5I, and VP3C, respectively).
      Other than the D5I mutant, the mutants formed CLPs when expressed in the presence
      of VP7. Subsequently, T7 tag epitopes were inserted into the D1I, D2I, and VP3C
      restriction sites and recombinant baculoviruses were generated to express
      chimeric VP3 proteins (VP3D1IT, VP3D2IT, and VP3CT). Each chimeric protein
      retained the ability to form CLPs when VP7 protein was provided. In another
      construction an immunogenic sequence representing a bovine leukemia virus (BLV)
      glycoprotein peptide was incorporated into the carboxy terminus of VP3 and the
      derived CLPs were used to raise antibodies that reacted with the BLV antigen. The
      results suggest that the VP3 molecule can accommodate foreign sequences at
      certain sites without perturbing their ability to form CLPs with VP7.

PMID- 8553562
TI  - Naturally occurring Sin Nombre virus genetic reassortants.
AB  - Genetic reassortment has been shown to play an important role in the evolution of
      several segmented RNA viruses and in the epidemiology of associated diseases. Sin
      Nombre (SN) virus is the cause of hantavirus pulmonary syndrome throughout the
      western United States. Like other hantaviruses, it possesses a genome consisting
      of three negative-sense RNA segments, S, M, and L. Recent analysis has
      demonstrated the presence of at least three different hantaviruses in Nevada and
      eastern California, including SN, Prospect Hill-like, and El Moro Canyon-like
      viruses. In addition, two distinct lineages of SN virus can be found in
      Peromyscus maniculatus rodents (sometimes in close proximity) trapped at study
      sites in this region. Data obtained by phylogenetic analysis of sequence
      differences detected among the S, M, and L genome segments of these SN viruses
      are consistent with reassortment having taken place between SN virus genetic
      variants. The results suggest that M (and to a lesser extent S or L) genome
      segment flow occurs within SN virus populations in P. maniculatus in this region.
      No reassortment was detected between SN virus and other hantavirus types present
      in the area. This finding suggests that as genetic distance increases, the
      frequency of formation of viable reassortants decreases, or that hantaviruses
      which are primarily maintained in different rodent hosts rarely have the
      opportunity to genetically interact.

PMID- 8553563
TI  - Infectious transcripts of tick-borne encephalitis virus, generated in days by RT
      PCR.
AB  - Construction of infectious clones of flaviviruses can be problematic owing to
      instability, toxicity, and recombination events occurring while cloning cDNA in
      the bacterial vectors. To overcome these difficulties we have devised a rapid and
      simple method for producing an infectious genetically engineered tick-borne
      encephalitis virus in less than 10 days using viral RNA from an unpurified virus
      suspension. The experimental protocol utilized the high fidelity reverse
      transcription-polymerase chain reaction to produce two long (5.7 and 5.2 kb)
      overlapping cDNA segments. To produce full-length cDNA the two overlapping
      segments were either ligated or fused by polymerase chain reaction. The cDNA was
      then transcribed and the derived full-length RNA was injected intracerebrally
      into young mice which reproduced the infectious virus within 8-20 days. To
      differentiate the engineered virus from parent virus, a Sunl restriction site was
      introduced by substituting nucleotides at positions 5688 and 5691 of the viral
      genome. This restriction site was present in the engineered virus recovered from
      infected mice. Antigenic and electrophoretic analysis of the proteins recovered
      from the engineered virus confirmed that it was indistinguishable from parent
      virus. In addition to its applicability as a rapid method of producing infectious
      engineered virus, this protocol offers the opportunity to introduce changes by
      site-directed mutagenesis without needing to clone the viral DNA. The method
      should be applicable to most viruses possessing an infectious RNA molecule and
      reduces the time required to produce a genetically engineered virus from years to
      days. When appropriate, the choice of mice for transfection of RNA has the
      advantage of being extremely simple, very sensitive, and producing high titers of
      stable virus.

PMID- 8553564
TI  - Intermediate forms of glycoconjugates are present in the envelope of herpes
      simplex virions during their transport along the exocytic pathway.
AB  - In cells infected with herpes simplex virus 1, intracellular virions in transit
      along the exocytic pathway carry glycoconjugates that react, in fracture-label
      technique, with helix pomatia lectin. This lectin is specific for unsubstituted N
      acetylgalactosamine, an intermediate sugar added in O-linkage to ser/thr residues
      in cis-Golgi and then substituted with galactose and sialic acid in the trans
      Golgi. Virions in the perinuclear space do not react with helix pomatia lectin.
      In intracellular transport vesicles and vacules, close to the Golgi complex,
      virions are positively labeled by helix pomatia lectin and variably labeled by
      wheat germ agglutinin, a lectin specific for fully mature glycoconjugates.
      Extracellular virions react only with wheat germ agglutinin. The detection of
      glycoconjugates at intermediate steps of maturation, coupled with previous
      results that virions in the perinuclear space carry high mannose oligosaccharides
      (Torrisi et al., J. Virol. 66, 554-561, 1992), favor the view that maturation of
      herpes simplex virion envelope proceeds in a stepwise manner along the exocytic
      pathway. Should transit of virions involve a deenvelopment of enveloped virions
      followed by reenvelopment of naked nucleocapsids, our results rule out
      reenvelopment at trans- or post-Golgi compartments and could be consistent with
      reenvelopment occurring earlier in the exocytic pathway, most likely at the cis
      Golgi.

PMID- 8553565
TI  - In vivo processing of Pr160gag-pol from human immunodeficiency virus type 1 (HIV)
      in acutely infected, cultured human T-lymphocytes.
AB  - The processing of the HIV-1 Pr160gag-pol precursor polyprotein was analyzed in
      freshly HIV-1-infected MT-4 cultured cells. Single intermediates of the
      processing cascade were characterized by immunoblotting using distinct antisera.
      A potent inhibitor of the HIV protease (PR), Ro 31-8959, was employed to block
      cleavage by the mature PR, thus allowing insights into initial stages of the gag
      pol (auto)-catalytical processing. While most known gag-pol cleavages were
      blocked in the presence of the inhibitor, the cleavage site between the gag-NC
      and the pol-p6 domains was still cleaved even in presence of high amounts (1
      microM) of inhibitor, leading to the accumulation of a novel 114-kDa polyprotein
      comprising p6-PR-RT-IN. In the absence of inhibitor no accumulation of p114 was
      observed. In inhibitor-treated, HIV-1-infected cells a p6-PR intermediate was
      also detected, indicating subsequent cleavage of the PR/RT scissile bond. These
      results demonstrate initial cleavage(s) of the gag-pol precursor hydrolyzed by a
      proteolytic activity different from the mature PR and indicate that p114 (p6-PR
      RT-IN) and p6-PR intermediates could play an essential role in the PR activation
      process.

PMID- 8553566
TI  - Preferential initiation at the second AUG of the measles virus F mRNA: a role for
      the long untranslated region.
AB  - In the measles virus fusion (F) mRNA, a 574-bases-long untranslated region (UTR),
      is followed by three clustered AUGs at codon positions 1 (AUG1), 4 (AUG2), and 15
      (AUG3). We established that only translation initiation on AUG1 or AUG2 leads to
      the synthesis of functional F proteins. In the presence of the UTR translation
      initiation occurs almost exclusively at AUG2. In its absence, the ribosomes
      initiate also from AUG1 or AUG3.

PMID- 8553567
TI  - Isolation of cytotoxic T lymphocytes from healthy seropositive individuals
      specific for peptide epitopes from Epstein-Barr virus nuclear antigen 1:
      implications for viral persistence and tumor surveillance.
AB  - The question of whether Epstein-Barr nuclear antigen 1 (EBNA1) includes cytotoxic
      T lymphocyte (CTL) epitopes has generated considerable scientific interest,
      primarily due to its important implications for the overall biology of Epstein
      Barr virus (EBV). Earlier studies have suggested that EBV-associated malignancies
      that express only EBNA1 escape virus-specific immune surveillance since this
      antigen is not a target for CTL recognition. In the present report we have used a
      modified protocol to demonstrate that EBNA1 includes sequences which can be
      recognized by both polyclonal and clonal CTLs. CD4+ CTL clones were isolated from
      a healthy, seropositive donor that recognized the peptide epitope TSLYNLRRGTALA
      from EBNA1 in association with HLA DR1. Interestingly, these CTLs are unable to
      lyse EBV-infected B cells suggesting that EBNA1 may not be endogenously processed
      and/or presented to the host CTL response. Despite recent suggestions that
      glycine-alanine repeat sequences within EBNA1 can inhibit endogenous processing,
      target cells infected with recombinant vaccinia vectors encoding truncated EBNA1
      proteins, without these repeat sequences, were not recognized by this CTL clone.
      Thus it seems that the presence of glycine-alanine repeats is not responsible for
      inhibiting the processing of the class II-restricted epitope defined in this
      study. These results substantiate the view that EBV-infected normal and malignant
      cells, where viral gene expression is limited to EBNA1, can resist CTL-mediated
      immune surveillance in vivo.

PMID- 8553568
TI  - Interaction of host proteins with the plus-strand promoter of brome mosaic virus
      RNA-2.
AB  - The binding of five barley proteins (Mr: 37, 36, 35, 34, and 30 kDa) to the ICR2
      motif present at the 5' end of brome mosaic virus (BMV) RNA-2 was identified
      using UV cross-linking. Evidence that the interaction is specific included the
      observation that these proteins did not recognize a similar-size RNA fragment
      transcribed from a nonviral (beta-glucuronidase) gene, nor did they bind to the
      3' end of the plus strand of RNA-3. Replication-defective BMV RNA-2 mutants
      bearing substitution mutations at nucleotides 9 and 10 of the ICR2 motif were
      used to show that these positions were involved in the interaction of the five
      barley proteins with BMV RNA-2. Surprisingly, the profile of barley proteins
      interacting with the 3' end of the minus strand of RNA-2 was similar to that seen
      for the 5' end of the plus strand. Further, the profile of proteins binding to
      minus-sense probes bearing substitution mutations in the ICR2 region differed
      from that found for the wild-type sequence. These findings support the concept
      that host proteins are involved in genome replication and that their ability to
      interact with both plus and minus strands of the viral RNA is probably involved
      with the initiation of plus-strand synthesis.

PMID- 8553569
TI  - Molecular basis for the resistance of influenza viruses to 4-guanidino-Neu5Ac2en.
AB  - We report the selection and characterization of influenza A/NWS-G70c and
      B/HK/8/73 (HG) viruses which are resistant to the potent influenza neuraminidase
      inhibitor, 4-guanidino-Neu5Ac2en. Viruses were selected which replicated in MDCK
      cells in the presence of 20 micrograms/ml inhibitor. The neuraminidase of
      resistant viruses was > 200-fold more resistant to 4-guanidino-Neu5Ac2en than was
      the neuraminidase of the parent viruses. Although amounts of neuraminidase
      protein were similar in resistant and parent viruses, the enzyme activity of the
      resistant neuraminidase heads was reduced by > 95% for the substrates used.
      Relative to parent viruses, the resistant viruses replicated to equal or greater
      titers in tissue culture and in embryonated chicken eggs. Sequence analysis
      revealed a single nucleotide mutation in the neuraminidase gene of each virus
      resulting in the change of the conserved Glu 119 (which lies in a pocket beneath
      the active site of the enzyme) to Gly thus eliminating an electrostatic
      interaction with the C-4 guanidinium moiety of the inhibitor. Mutations (Asn-
      >Ser) at amino acids 145 and 150 were also found in the hemagglutinin gene of the
      B/HK/8/73 (HG) virus resistant to 4-guanidino-Neu5Ac2en. No changes were found in
      the hemagglutinin gene of the resistant A/NWS-G70c virus.

PMID- 8553570
TI  - The carboxy-terminal domain is essential for stability and not for virion
      incorporation of HIV-1 Vpr into virus particles.
AB  - Vpr is one of the auxiliary gene products encoded by HIV-1 genome. Vpr is a 14
      kDa protein and exhibits several interesting characteristics including
      incorporation into virus particles, oligomerization, localization in the nucleus,
      and positive regulation of virus replication in primary cells. In an effort to
      define the structure-function relationship of Vpr, the role of the C-terminus of
      Vpr was investigated. Site-specific mutagenesis involving deletion, insertion,
      and substitution of residues at the C-terminus was utilized to generate variants
      of Vpr. Mutations introduced at the C-terminus affected properties of Vpr in
      different ways: (i) Vpr containing amino acids 1-72 showed the virion
      incorporation phenotype, indicating that the C-terminus is not essential for this
      function, (ii) the C-terminus contributes to the stability of Vpr, and (iii)
      substitution mutagenesis involving the basic residues showed stability similar to
      that of wild type, indicating the lack of involvement of these residues in this
      biochemical property of Vpr. The data generated in this study and our early
      mutagenic analyses on Vpr suggest that domains noncontiguous in primary sequence
      contribute to the stability of Vpr through overall conformation of the protein.

PMID- 8553571
TI  - Human PKR transfected into murine cells stimulates expression of genes under
      control of the HIV1 or HTLV-I LTR.
AB  - We have analyzed the effect of transfection into murine NIH/3T3 cells of the
      human dsRNA-activated kinase PKR on the expression of the beta-galactosidase
      reporter gene, placed under control of the HIV1 or the HTLV-I LTR. beta
      Galactosidase expression is stimulated when the reporter plasmids are
      cotransfected with wild-type PKR but inhibited when cotransfected with a
      catalytically inactive mutant PKR. In the case of HIV1, beta-galactosidase
      expression was not stimulated when cotransfection was carried out with PKR
      harboring mutations in the dsRNA binding domains, indicating that stimulation
      depends on the classical mode of PKR activation through dsRNA binding. In
      contrast, the dsRNA binding mutants of PKR could still partially stimulate beta
      galactosidase expression from the HTLV-I LTR, suggesting that PKR activation in
      this case may involve different/additional mechanisms. These results show that,
      in addition to the known down-regulation of protein synthesis through elF2
      phosphorylation, PKR can also positively stimulate gene expression in vivo, most
      probably through phosphorylation of a substrate distinct from elF2.

PMID- 8553572
TI  - Cis-acting elements of the encephalomyocarditis virus internal ribosomal entry
      site.
AB  - Translation initiation of encephalomyocarditis virus (EMCV) mRNA occurs by
      ribosomal entry into the 5' untranslated region. Internal ribosome binding to
      EMCV mRNA requires a viral cis-acting element, termed the internal ribosomal
      entry site (IRES), and cellular trans-acting factors. The polypyrimidine tract
      binding protein (PTB) has been identified as one such trans-acting factor
      required for EMCV IRES-dependent translation. Using a dicistronic mRNA and an in
      vitro translation system, we have identified cis-acting elements of the EMCV IRES
      required for IRES-dependent translation. The results identify several regions of
      the IRES that are required for efficient IRES-dependent translation, including
      the PTB binding site. Other regions of the IRES may act only as spacer sequences,
      analogous to the spacer sequences found in rhinovirus and enterovirus IRES
      elements, to link essential regions of the IRES together. The flexibility of one
      region of the EMCV IRES was demonstrated by an insertion of 125 nucleotides that
      had little effect on IRES function while the constraint imposed on another region
      was demonstrated by a 3-nucleotide deletion that nearly abolished IRES-dependent
      translation.

PMID- 8553573
TI  - Sequence variation in the capsid protein genes of human papillomavirus type 16
      and type 31.
AB  - The sequences of the capsid genes of a human papillomavirus type 16 (HPV 16) DNA
      and an HPV 31 DNA were determined. The HPV 16 DNA contained genes coding for the
      most variable HPV 16 capsid proteins yet identified (17 variable amino acids).
      Three of six coding changes in the HPV 31 DNA occurred at positions equivalent to
      ones where variable amino acids in HPV 16 have been observed. Variable amino
      acids in both viruses occurred predominantly in regions which showed amino acid
      variation when closely related types of HPV were compared; thus, most of the
      factors which determined the intratypic variation in the capsid proteins of the
      viruses described here were likely the same as those which determined differences
      between the capsid proteins of different HPV types.

PMID- 8553574
TI  - The African swine fever virus IAP homolog is a late structural polypeptide.
AB  - The analysis of the complete nucleotide sequence of the African swine fever virus
      genome has revealed the existence of a number of genes potentially capable of
      modifying the host's response to the virus infection. In this report, we describe
      the results of the characterization of the A224L gene that encodes a novel member
      of the family of apoptosis inhibitors known as IAP proteins. A224L is expressed
      during the late phase of the infectious cycle, and its polypeptide product is
      assembled into virus particles.

PMID- 8553575
TI  - Epstein-Barr virus nuclear antigen 2-estrogen receptor fusion proteins
      transactivate viral and cellular genes and interact with RBP-J kappa in a
      conditional fashion.
AB  - Epstein-Barr virus nuclear antigen 2 (EBNA2) is a transcriptional activator of
      viral and cellular genes involved in B cell transformation by EBV and is targeted
      to EBV responsive promoters through interaction with cellular DNA binding
      proteins such as RBP-J kappa. To develop a conditional system in which the
      function of EBNA2 can be switched on and off, we have fused the hormone binding
      domain of the estrogen receptor to the N- or C-terminus of EBNA2. Here we show
      that after transient or stable transfer of these chimerical EBNA2 genes into
      human B cell lymphoma lines, transactivation of LMP1, TP1, and TP2 promoter
      constructs, expression of the cell surface markers CD21 and CD23, and binding of
      EBNA2 to its cellular partner RBP-J kappa are dependent on the presence of
      estrogen. The EBNA2 fusion proteins proved to be virtually inactive in the
      absence of hormone.

PMID- 8553576
TI  - Rapid generation of antibodies against the HTLV-II external envelope protein by
      growth of mouse plasmacytomas in SCID mice.
AB  - Recombinant human T-cell leukemia virus type II (HTLV-II) envelope external
      glycoprotein, gp46-II, was expressed using a vaccinia virus vector. A recombinant
      gp46-II fused to an epitope of the influenza virus hemagglutinin, YPYDVPDYA, was
      purified by immunoaffinity chromatography. The purified glycoprotein was used to
      immunize Balb/c mice, and antibodies against gp46-II were detected by Western
      blot analysis and syncytium inhibition assays. We transformed spleen cells from
      the immunized mice by retroviral infection with ABL-MYC (psi 2) and
      intraperitoneally transplanted the infected cells into syngeneic Balb/c and
      severe combined immunodeficient (SCID) mice. The plasmacytomas established
      ascitic tumors that produced antibodies directed against HTLV-II gp46-II. Ascites
      developed more rapidly in SCID mice than in normal syngeneic mice. This procedure
      provides a general means to generate antibodies rapidly.

PMID- 8553577
TI  - Infectious proviral clones of chimpanzee foamy virus (SFVcpz) generated by long
      PCR reveal close functional relatedness to human foamy virus.
AB  - Infectious proviral clones of simian foamy virus isolated from chimpanzee
      (SFVcpz) were generated by long PCR. Two overlapping fragments representing the
      complete provirus were amplified from genomic DNA of infected cells. Four 8.8-kbp
      amplimers extending from base 1 of the provirus into the env gene and five 4.45
      kbp amplimers reaching from env to the end of the 3'-LTR were cloned into pCR II.
      Subsequently, the proviral fragments were combined in a chessboard manner to
      generate 20 plasmids containing full-length proviral DNA. Four plasmids produced
      infectious virus after transfection of susceptible cells. A distinct proviral
      form bearing a deletion in the transactivator gene joining both exons of a second
      regulatory gene present in wild-type foamy virus-infected cells started to emerge
      48 hr after transfection of BHK cells with infectious SFVcpz DNA. This
      observation supports a novel hypothesis to explain establishment of foamy virus
      latency. The transactivator protein Taf of SFVcpz transcomplemented for the
      homologous protein Bel-1 of the unique human foamy virus isolate (HFV) and Bel-1
      exhibited the reciprocal activity, suggesting that HFV could represent a variant
      of chimpanzee foamy virus.

PMID- 8553578
TI  - Phylogenetic analysis of open reading frame 5 of field isolates of equine
      arteritis virus and identification of conserved and nonconserved regions in the
      GL envelope glycoprotein.
AB  - The variation and phylogenetic relationship of open reading frame 5 (ORF5) of 3
      different laboratory strains of the original prototype Bucyrus strain of equine
      arteritis virus (EAV), the modified live virus vaccine (ARVAC, Fort Dodge
      Laboratories), and 18 field isolates of EAV from North America and Europe were
      determined by comparison of their gene sequences. The viruses differed from the
      published sequence by between 3 (99.6% homology) and 94 (87.8%) nucleotides and
      by between 3 (98.8%) and 24 (90.6%) amino acids. The field isolates differed from
      each other by between 2 (99.7%) and 110 (85.7%) nucleotides and by between 1
      (99.6%) and 26 (89.8%) amino acids. Comparison of the nucleotide sequences of
      these viruses indicates that although they are very closely related, the ORF5 of
      each virus is distinct. The ORF5 of EAV encodes the GL envelope glycoprotein
      which expresses the neutralization determinants of the virus. Comparative
      analysis of the deduced amino acid sequence of the GL protein of the viruses
      identified three distinct variable regions (V1 [aa 61-121], V2 [141-178], and V3
      [aa 202-222]), a putative signal sequence (S [aa 1-18]), and four conserved
      regions (C1 [aa 19-60], C2 [aa 122-140], C3 [aa 179-201], and C4 [aa 223-255]).
      Amino acid substitutions in the V1 region of the GL protein of EAV field isolates
      had significant effects on the predicted hydrophobicity and secondary structure
      of the protein, which is potentially important because this region contains a
      major neutralization site. Estimation of genetic distances and phylogenetic tree
      analysis of these viruses identified four distinct groups of EAV isolates,
      including two North American (NA1 and NA2) and two European (E1 and E2) groups.
      The sequence data obtained from individual European and North American isolates
      suggest movement of viruses between the two continents.

PMID- 8553579
TI  - In vitro propagation and production of hepatitis E virus from in vivo-infected
      primary macaque hepatocytes.
AB  - Hepatitis E virus (HEV) is responsible for sporadic cases as well as large
      epidemics of acute viral hepatitis in many developing countries. The nucleotide
      sequence of HEV appears to be unique among known viruses and thus may represent a
      prototype human pathogen in a novel class of single-stranded, positive-sense RNA
      viruses. To facilitate further studies of the biology of HEV, a tissue culture
      system using a serum-free medium formulation has been developed to propagate the
      virus in vitro. Hepatocytes were isolated from livers of cynomolgus macaques
      experimentally infected with a HEV (Burma strain) inoculum and maintained in long
      term cultures. Using a highly strand-specific RT-PCR assay, both the positive
      sense and the negative replicative strands of HEV RNA were detected in these
      hepatocytes throughout the course of the experiments. Positive-strand genomic RNA
      was also detected in the culture medium, suggesting the production and secretion
      of HEV virus particles. The virus particles were successfully concentrated 200
      fold from the medium using ultrafiltration, and they could be observed by
      immunoelectron microscopy using anti-HEV-positive immune serum. These results
      demonstrate the capacity of this hepatocyte culture system to replicate HEV in
      vitro, thus providing an experimental means to study the replicative process of
      the virus.

PMID- 8553580
TI  - Influence of ORF2 on host cell tropism of feline immunodeficiency virus.
AB  - Feline immunodeficiency virus (FIV) is a lentivirus associated with an
      immunodeficiency syndrome of the domestic cat. A short open reading frame (ORF2),
      of unknown function, is present in all FIV isolates. We have investigated the
      role of ORF2 in determining the cell tropism of two infectious molecular clones
      of FIV. FIV-PPR is able to productively infect feline peripheral blood leukocytes
      (PBLs) and a T lymphocyte cell line (MCH5-4), but not a feline astrocyte cell
      line (G355-5) or Crandell feline kidney cells (CrFK). In contrast, FIV-34TF10 is
      able to productively infect G355-5 and CrFK cells, but not PBLs or MCH5-4 cells.
      The major difference in these FIV clones is that ORF2 in FIV-PPR is capable of
      encoding a 79-amino-acid peptide, whereas there is a stop codon in ORF2 after 43
      amino acids in FIV-34TF10. We performed site-directed mutagenesis to change the
      stop codon (TGA) in FIV-34TF10 to a tryptophan (TGG), the amino acid present at
      this location in FIV-PPR. FIV-34TF10 with ORF2 repaired (FIV-ORF2rep)
      productively infected PBLs, MCH5-4 cells, and primary macrophages, as well as
      CrFK and G355-5 cells, indicating that a protein encoded by ORF2 plays a role in
      determining the host cell tropism of FIV. ORF2 contains hydrophobic, acidic, and
      leucine-rich domains similar to those shown to be important for transactivating
      proteins of other lentiviruses. Coexpression of a plasmid expressing the ORF2
      gene product with another construct expressing the chloramphenicol acetyl
      transferase (CAT) gene driven by the FIV LTR, resulted in transactivation of CAT
      expression in both feline and human cells.

PMID- 8553581
TI  - Protection of nude mice by passive immunization with a type-common human
      recombinant monoclonal antibody against HSV.
AB  - Herpes simplex viral disease is an important cause of morbidity and mortality in
      man. Although the development of very effective nucleoside analogs with a high
      therapeutic index has greatly improved the clinical management of herpetic
      infections, the emergence of drug-resistant viral strains has become a cause of
      serious concern both because of its clinical implications and in terms of viral
      ecology. The present report is the first demonstration of the in vivo protective
      activity of a type-common human recombinant monoclonal antibody derived from a
      combinatorial antibody library. Athymic nude mice were infected with HSV type 1
      either intracutaneously in the flank or by corneal scarification. Beside reducing
      morality rates when administered before infection, the antibody dramatically and
      significantly prolonged survival times (P < 0.0001) when administered up to 24 hr
      postinfection, a time when the virus had already reached the peripheral nervous
      system. This suggests that the antibody may act, at least in part, by interfering
      with axonal transport of the virus and/or with viral expression. These results
      indicate that human recombinant antibodies isolated by antigen selection from
      combinatorial libraries can be effective in vivo. Such antibodies could
      complement antiviral chemotherapy and represent valuable tools for the
      prophylaxis of infections by the herpes simplex viruses.

PMID- 8553582
TI  - Priming of measles virus-specific CTL responses after immunization with a CTL
      epitope linked to a fusogenic peptide.
AB  - In this study, the potential of the amino-terminal sequence from the F1
      polypeptide responsible for the fusion of measles virus (MV) with cell membranes
      as a carrier system for a CTL epitope from the MV nucleoprotein was examined. The
      addition of the fusion sequence (FP) at either the amino or the carboxyl terminus
      of the CTL epitope peptide rendered it immunogenic after intraperitoneal
      immunization in mice. The CTLs induced were able to lyse target cells pulsed with
      the peptide or persistently infected with MV. After intranasal administration of
      a FP-CTL chimera with or without cholera toxin B subunit (CTB) as an adjuvant,
      CTL responses to the peptide pulsed and to MV-infected target cells were
      detected. Responses in groups of mice where CTB was used as an adjuvant were
      stronger. However, intranasal administration of the CTL epitope did not induce a
      protective response against intracranial challenge with a neuroadapted strain of
      MV. These findings highlight the potential of fusion sequences as a carrier
      system for CTL epitopes and the potential of the intranasal route for
      administration of synthetic peptides representing MV sequences.

PMID- 8553583
TI  - Myxoma virus M-T7, a secreted homolog of the interferon-gamma receptor, is a
      critical virulence factor for the development of myxomatosis in European rabbits.
AB  - Myxoma virus is a leporipoxvirus of New World rabbits (Sylvilagus sp.) that
      induces a rapidly lethal infection known as myxomatosis in the European rabbit
      (Oryctolagus cuniculus). Like all poxviruses, myxoma virus encodes a plethora of
      proteins to circumvent or inhibit a variety of host antiviral immune mechanisms.
      M-T7, the most abundantly secreted protein of myxoma virus-infected cells, was
      originally identified as an interferon-gamma receptor homolog (Upton, Mossman,
      and McFadden, Science 258, 1369-1372, 1992). Here, we demonstrate that M-T7 is
      dispensable for virus replication in cultured cells but is a critical virulence
      factor for virus pathogenesis in European rabbits. Disruption of both copies of
      the M-T7 gene in myxoma virus was achieved by the deletion of 372 bp of M-T7
      coding sequences, replacement with a selectable marker, p7.5Ecogpt, and selection
      of a recombinant virus (vMyxlac-T7gpt) resistant to mycophenolic acid. vMyxlac
      T7gpt expressed no detectable M-T7 protein and infected cells supernatants were
      devoid of any detectable interferon-gamma binding activities. Immunohistochemical
      staining with anti-beta-galactosidase and anti-CD43 antibodies demonstrated that
      in vMyxlac-T7gpt-infected rabbits the loss of M-T7 not only caused a dramatic
      reduction in disease symptoms and viral dissemination to secondary sites, but
      also dramatically influenced host leukocyte behavior. Notably, primary lesions in
      wild-type virus infections were generally underlayed by large masses of
      inflammatory cells that did not effectively migrate into the dermal sites of
      viral replication, whereas in vMyxlac-T7gpt infections this apparent block to
      leukocyte influx was relieved. A second major phenotypic distinction noted for
      the M-T7 knockout virus was the extensive activation of lymphocytes in secondary
      immune organs, particularly the spleen and lymph nodes, by Day 4 of the
      infection. This is in stark contrast to infection by wild-type myxoma virus,
      which results in relatively little, if any, cellular activation of germinal
      centers of spleen and lymph node by Day 4. We conclude that M-T7 functions early
      in infection to (1) retard inflammatory cell migration into infected tissues and
      (2) disrupt the communication between sentinel immune cells at the site of
      primary virus infection in the subdermis and lymphocytes in the secondary
      lymphoid organs, thereby disabling the host from mounting an effective cellular
      immune response. To summarize, in addition to neutralizing host interferon-gamma
      at infected sites, we propose that M-T7 protein also modifies leukocyte traffic
      in the vicinity of virus lesions, thus effectively severing the link between
      antigen presenting cells of the infected tissue and the effector lymphocytes of
      the peripheral immune organs.

PMID- 8553584
TI  - Mechanism of interferon action. Biochemical and genetic evidence for the
      intermolecular association of the RNA-dependent protein kinase PKR from human
      cells.
AB  - The interferon-inducible protein kinase (PKR) is activated by an RNA-dependent
      autophosphorylation. Structure-function studies of the 551 amino acid PKR kinase
      from human cells have revealed that catalytic-deficient PKR mutants such as PKR(1
      551)K296R display a dominant negative behavior when expressed in transfected
      cells. The potential for PKR to form protein multimers has therefore been
      examined. Three types of studies, including both genetic and biochemical
      analyses, demonstrated that PKR from human cells undergoes an intermolecular
      association that is not dependent upon RNA. First, the intermolecular association
      of PKR in vitro was demonstrated in the context of an enzyme-substrate
      interaction. Purified recombinant histidine-tagged PKR(1-551)K296R mutant protein
      was phosphorylated by purified wild-type PKR; this intermolecular phosphorylation
      of PKR was dependent on double-stranded RNA. At a fixed RNA concentration, high
      concentrations of the HIS-PKR(1-551)K296R mutant both impaired the
      autophosphorylation of wild-type PKR and blocked the trans-phosphorylation of
      itself. Second, the yeast two-hybrid system was used to probe the intermolecular
      association of PKR in vivo. Coexpression of the full-length catalytic-deficient
      phosphotransfer mutant PKR(1-551)K296R as a fusion protein with the Gal4
      activation domain and the Gal4 DNA binding domain resulted in the expression of
      two Gal4-responsive reporter genes, HIS3 and lacZ. The full-length RNA-binding
      deficient PKR(1-551)K64E/K296R double mutant also interacted with PKR(1-551)K296R
      sufficiently to activate Gal4-responsive reporter genes; however, other PKR
      mutants including PKR(1-280)wt and PKR(281-551)K296R as well as p53, RAS, and
      BCL2 did not. Third, both PKR(1-551)K296R and PKR(1-551)K64E/K296R enhanced the
      expression of the reovirus S1 gene and S1/S4 chimeric gene in cotransfected COS
      cells. By contrast, the expression of the reovirus S4 gene was not enhanced by
      cotransfection with either PKR(1-551)K296R or PKR(1-551)K64E/K296R. These results
      indicate that PKR interacts with itself in an intermolecular manner both in vivo
      and in vitro, and that RNA binding is neither necessary nor sufficient for PKR
      multimerization.

PMID- 8553585
TI  - In vitro production of stable Epstein-Barr virus-positive epithelial cell clones
      which resemble the virus:cell interaction observed in nasopharyngeal carcinoma.
AB  - The interaction of Epstein-Barr virus (EBV) with epithelial cells and the
      consequent role of the virus in the aetiology of undifferentiated nasopharyngeal
      carcinoma (NPC) is poorly understood. One important obstacle to work in this area
      has been the lack of an epithelial cell culture system in which EBV is stably
      maintained. Using a previously described approach in which CR2-transfected
      epithelial cells (SVK-CR2) are rendered susceptible to transient EBV infection
      (Li et al., Nature 356, 347, 1992), we now demonstrate that the pattern of EBV
      latent gene transcription in these acutely infected epithelial cells differs from
      that observed in virus-infected primary B cells. In addition, some of these
      epithelial cells spontaneously entered the EBV lytic cycle. By cloning Akata
      virus-infected SVK-CR2 cells we generated two stable lines which remained EBV
      positive for more than 1.5 years at which time further subclones were isolated.
      These cloned lines carry the EBV genome as an episome and exclusively use the FQp
      promoter for driving EBNA1 transcription, display no Cp/Wp promoter activity, and
      express low levels of the LMP mRNAs. Unlike acutely infected SVK-CR2 cells, the
      cloned lines responded poorly to suspension-induced terminal differentiation and
      were impaired in their ability to enter the virus lytic cycle. These results,
      showing similarities between the cloned EBV-positive SVK-CR2 lines and NPC tumour
      cells, suggest that stable maintenance of EBV in epithelial cells may require an
      undifferentiated cellular environment.

PMID- 8553586
TI  - Transmission of HIV-1 from productively infected mature Langerhans cells to
      primary CD4+ T lymphocytes results in altered T cell responses with enhanced
      production of IFN-gamma and IL-10.
AB  - Mature Langerhans cells (mLC), the ex vivo correlates of interdigitating
      dendritic cells (IDC), are susceptible to infection with HIV-1. As IDC are
      important activators of T helper (Th) cells in vivo, we examined the interaction
      of HIV-1-infected mLC with CD4+ T lymphocytes. HIV-1-infected mLC readily formed
      clusters with the T cells and efficiently transmitted HIV-1 to the CD4+ Th cells.
      Formation of syncytia between mLC and T cells was initiated by HIV-1-infected
      mLC. In the clusters of HIV-1-infected mLC and activated T cells a massive HIV-1
      production was observed leading to the subsequent elimination of the activated
      and infected T helper cells. Examination of the cytokine pattern produced during
      interaction of infected mLC with CD4+ T cells revealed an enhanced production of
      IFN-gamma and IL-10 in the cocultures. These results suggest that during antigen
      presentation-driven T cell activation by IDC in the lymphoid tissues, HIV-1
      infected IDC might efficiently transmit the virus to Th cells, leading to altered
      Th cell responses.

PMID- 8553587
TI  - Nucleotide sequence and molecular analysis of the rhesus cytomegalovirus
      immediate-early gene and the UL121-117 open reading frames.
AB  - Cytomegalovirus (CMV) has been isolated from many nonhuman primates, including
      rhesus macaques (Macaca mulatta). To better understand the molecular biology of
      rhesus CMV (RhCMV), a 9.2-kb DNA restriction fragment spanning the immediate
      early (IE) gene has been molecularly cloned and sequenced. Open reading frames
      (ORF) have been identified and transcripts mapped for regions corresponding to
      exons 1, 2, 3, and 4 of the IE1 protein of human CMV (HCMV) and to exons 1, 2, 3,
      and 5 of IE2. The predicted RhCMV IE1 protein was 29 and 40% identical with the
      HCMV and African green monkey (AGM) CMV IE1 proteins, respectively, and the
      predicted RhCMV IE2 protein was 48 and 65% identical with the HCMV and AGM CMV
      IE2 proteins, respectively. Five additional ORF 3' to the RhCMV IE gene were
      identified which contained significant homologies with the HCMV UL121-UL117 ORF.
      The predicted translation products ranged from 29 to 47% identical with, and 52
      to 66% similarity to the corresponding ORF of HCMV. Conservation of nucleic and
      amino acid sequences, and colinearity of genes, between primate CMV genomes
      contribute to a better understanding of primate CMV evolution, regulation, and
      pathogenesis.

PMID- 8553588
TI  - Human papillomavirus E7 oncoproteins bind a single form of cyclin E in a complex
      with cdk2 and p107.
AB  - The E6 and E7 proteins of the high-risk human papillomaviruses (HPVs) act
      coordinately to immortalize human keratinocytes. These viral oncoproteins
      function by binding and altering the activity of cellular proteins which regulate
      cell cycle progression. Among the proteins bound by E7 are the retinoblastoma
      protein, Rb, as well as the related p107 and p130 proteins. In addition, E7 binds
      cyclin A, which regulates transit through the S and G2/M phases of the cell
      cycle. In this study, we demonstrate that HPV 18 E7 also associates with cyclin E
      which controls the G1/S transition. E7/cyclin E complexes were immunoprecipitated
      from E7-expressing cells as well as from cell extracts using GST-E7 fusion
      proteins. E7 was found to complex with a single form of cyclin E, and the binding
      was mediated through p107. Both E7/cyclin E and E7/cyclin A complexes exhibit
      kinase activity through associated cdk2 proteins which can contribute to
      phosphorylation of p107. The association of E7 with proteins which regulate
      transit through the cell cycle may provide an additional mechanism by which
      infection with human papillomaviruses results in cellular hyperproliferation.

PMID- 8553589
TI  - Natural isolates of ECHO virus type 25 with extensive variations in IRES
      sequences and different translational efficiencies.
AB  - The complete nucleotide sequence of the 5'-untranslated region (5'-UTR) of the
      genome of three ECHO virus type 25 strains (the JV4 reference strain and two wild
      isolates) was determined. The 5'-UTR of the two isolates shared 85 and 82%
      nucleotide identity with the reference strain. The overall folding of the
      predicted secondary structure of the ECHO virus 5'-UTRs showed significant
      conservation with that of the poliovirus. Most significant differences were
      observed in specific domains of the predicted IRES of the wild isolates. The
      efficiency with which ECHO virus type 25 5'-UTRs promoted internal initiation of
      translation was examined in an in vitro translation system. At low doses of input
      RNA, all three 5'-UTRs were similarly efficient in promoting internal ribosome
      entry and behaved similarly to the poliovirus IRES in that downstream cistron
      translation was markedly stimulated by the addition of HeLa cell extracts to
      standard reticulocyte lysates. At high RNA doses, the JV4 5'-UTR was much more
      efficient than the other two ECHO virus 5'-UTRs. This difference was much less
      marked when reticulocyte lysates were supplemented with 20% HeLa S-10 extracts,
      which suggests that the two less efficient 5'-UTRs were characterized by a
      reduced binding capacity to at least one factor present in HeLa cells. In MRC5
      cell S-10 extract, internal initiation of translation was stimulated from the
      IRES of all three ECHO strains, the M1262 IRES being the least stimulated.

PMID- 8553590
TI  - SIVsmmPBj14 induces expression of a mucosal integrin on macaque lymphocytes.
AB  - The PBj14 isolate of simian immunodeficiency virus, SIVsmmPBj14, is an acutely
      pathogenic lentivirus that causes severe gastrointestinal disease in macaque
      monkeys. The studies reported here examine the basis for the enteropathic
      phenotype of SIVsmmPBj14, using flow cytometric analysis of cultured macaque
      lymphocytes and immunohistochemical staining of tissue specimens from virus
      infected macaques. The data show that enteropathic molecular clones of
      SIVsmmPBj14 induce expression of the alpha E beta 7 integrin, which is believed
      to mediate mucosal retention of T-cells, whereas molecular clones from
      nonenteropathic derivatives of SIVsmmPBj14 do not do so. Thus, elevated
      expression of alpha E beta 7 may ber responsible, at least in part, for the
      accumulation of abnormally large numbers of T-cells within the intestinal mucosa
      during acute SIVsmmPBj14 infection.

PMID- 8553591
TI  - [Symptomatic and silent myocardial ischemia during drug therapy and after
      aortocoronary bypass].
AB  - In 53 patients with stable angina pectoris 24-hour ambulatory
      electrocardiographic monitoring (Holter) and bicycle ergometry were used before
      and six months after a coronary bypass. The examination before operation was made
      while anti-ischaemic medication was administered, the examination after
      revascularization was done without medication. The patients were divided into
      group A (31 patients where complete revascularization of the myocardium was made)
      and group B (22 patients with incomplete revascularization) and the results were
      compared during medication and after aortocoronary bypass. In patients of group A
      revascularization prolonged significantly the load period during ergometry, as
      compared with medication (from 7.2 +/- 2.2 min. to 9.1 +/- 2.4 min., p < 0.01),
      the depression of the ST segment in lead V5 was reduced (from 1.3 +/- 0.8 mm to
      0.8 +/- 1.0 mm, p < 0.05) and the number of painful episodes during Holter
      monitoring (from 1 +/- 1 to 0, p < 0.01). In patients of group B none these
      parameters improved. Medicamentous treatment eliminated ischaemia during a load
      in 16% of patients in group A, while revascularization did so in 61% (p < 0.01).
      In patients of group B the success rate of medication was 9%, in
      revascularization 14% (p = n.s.). During Holter monitoring after
      revascularization no episodes of ST depressions associated with anginous pain
      were recorded, although the mean number of silent episodes of ST depressions per
      24 hours was 6 +/- 8 in patients of group B and 1 +/- 2 in patients of group A.
      In patients with stable angina pectoris complete revascularization is
      significantly more effective than anti-ischaemic medication as regards tolerance
      of loads and suppression of myocardial ischaemia. Silent myocardial ischaemia is
      frequent after aortocoronary bypasses and its possible occurrence should be taken
      into account, in particular in patients with incomplete revascularization.

PMID- 8553592
TI  - [Spirapril in the therapy of mild and moderately severe hypertension. A Czech and
      Slovak multicenter study].
AB  - A one-year open study was focused on the therapeutic effect and tolerance of
      spirapril in 171 patients with mild to moderate hypertension in 11 centres in the
      Czech and Slovak Republic. The antihypertensive effectiveness was investigated
      after four weeks, after 12 weeks and after 52 weeks. Only the results recorded
      after one year are reported. The study was completed after one year by 139
      patients, incl. 120 (86.3%) with a normal diastolic pressure of 90 mmHg or less.
      The study was not completed by 32 patients (18.8%): because treatment was not
      effective--9.4%, because of undesirable effects--4.7%, 3.5% were eliminated by
      the investigators for various reasons (change of domicile, poor collaboration)
      and 1.2% because the protocol was not respected. According to the analysis
      "intention to treat" the diastolic pressure was normalized by monotherapy with
      spirapril in 25.1% of the baseline group; combination of spirapril with
      bopindolol led to normalization of the pressure in another 38.0% patients and in
      7.0% patients normal diastolic pressure was achieved by a combination of
      spirapril with a hydrochlorothiazide; i.e. a total of 70.1% of the baseline group
      had a normal diastolic pressure after one year of treatment. In another 9.4% of
      the baseline group the diastolic pressure declined by 10 mmHg or more but not to
      normal levels. Thus normalization or effective control of pressure was achieved
      after one year in 79.6% patients according to the analysis "intention to treat".
      The combination of spirapril and bopindolol proved very effective. Patients where
      it was necessary to combine spirapril with bopindolol or hydrochlorothiazide had
      significantly higher baseline readings of blood pressure. During treatment the
      authors did not record in any of the groups a change of lipids, potassium, uric
      acid, the haemogram, liver tests or creatinine. Treatment was well tolerated and
      undesirable effects were rare (most frequent side effects: cough 3.5%, vertigo
      also 3.5%). The results of the study indicate that spirapril is an effective and
      well tolerated ACE inhibitor in the treatment of hypertension and its combination
      with bopindolol is equally suitable as the combination of spirapril with
      hydrochlorothiazide.

PMID- 8553593
TI  - [Determination of dry weight of hemodialyzed patients on the basis of the ratio
      of extracellular fluid volume to total body fluid volume as measured by
      multifrequency impedance].
AB  - Whole body impedometry is relatively new non-invasive method to measure the
      distribution of total body water (TBW) between extra- and intracellular
      compartment (VEC, VIC). Having applied linear regression analysis onto the
      relation of the ratio of the extracellular volume to the volume of total body
      water (VEC/TBW) and the age in a group of healthy individuals very narrow scatter
      from the regression line was found. This line can thus be used as an indicator of
      normohydration status with respect to age. Assuming that the relation of VEC/TBW
      vs. age is the same in dialysed patients and that the state of normohydration
      corresponds to the so called dry weight, the VEC/TBW value can be used as a novel
      indicator of dry weight. Any deviation of the pre-dialysis VEC/TBW value from
      normal could easily be used to establish the desired ultrafiltration and dry
      weight. With regard to the known inaccuracy with which the dry weight is
      determined from purely clinical assessment this approach may lead to substantial
      objectivisation in determination of this principal parameter. It may be
      especially helpful in case of newly admitted patients. The suggested new approach
      to dry weight determination is supported by the finding of statistically
      significant relation between post-dialysis deviation of the VEC/TBW ratio from
      the normal value vs. blood volume reduction at the end of the dialysis session.
      Patients classified at the end of a dialysis session as still overhydrated by
      their VEC/TBW deviation from normal showed little or no reduction in their blood
      volume. An investigation of the Vena Cava Inferior diameter in a subgroup of
      these patients confirmed this finding showing no decrease at the end of dialysis.
      On the contrary, the patients whose post-dialysis VEC/TBW value was normal or
      below normal showed both significant reduction in their blood volume as well as
      decrease in the Vena Cava Inferior diameter.

PMID- 8553594
TI  - [Personal experience with replacement therapy with intravenous gamma globulin].
AB  - Replacement therapy with intravenous immunoglobulin (IVIG) is currently the
      therapy of choice in patients with antibody-formation deficiency. Our 30-month
      experience with IVIG treatment in 8 patients with common variable
      immunodeficiency and in 4 patients with x-linked agammaglobulinemia previously
      treated by intramuscular immunoglobulin or low-dose IVIG is presented. Long-term
      dosage was 400 mg/kg once in 3--4 weeks. Ten patients reported an improvement of
      their health state, especially the signs of their chronic bronchitis improved.
      Compared to 2 cases of pneumonia which occurred within 30 months before IVIG
      therapy had started, no case of pneumonia occurred during IVIG treatment.
      Infusion rate of 4 mg/kg/min was safe enough in 11 of our patients. Serum trough
      IgG level is the most important for laboratory monitoring of the patients under
      IVIG therapy.

PMID- 8553595
TI  - [Rheumatoid pericarditis: correlation with immunologic parameters].
AB  - In 35 patients with rheumatoid pericarditis the laboratory findings were compared
      with those of a group of 65 patients with rheumatoid arthritis without a
      pericardial exudate. The authors assessed the red cell sedimentation rate and
      serum levels of immunoglobulins G, M, A, semiquantitative values of the
      rheumatoid factor, circulating immunocomplexes, C3 and C4 complement components,
      the positivity of antinuclear antibodies and values of C-reactive protein. The
      authors found significantly elevated values of immunoglobulins M in patients with
      rheumatoid arthritis without a pericardial exudate. As regards the other
      investigated parameters the two compared groups did not differ.

PMID- 8553596
TI  - [Evaluation of treatment of anemia with erythropoietin in patients with multiple
      myeloma].
AB  - Multiple myeloma is very frequently associated with anaemia which has the
      character of hypo-proliferative anaemia of chronic diseases. In this type of
      anaemia the erythropoietin formation is frequently inadequate. According to data
      in the literature pharmacological doses of erythropoietin lead to an increase of
      the haemoglobin concentration in blood. Erythropoietin (Eprex Cilag) was
      administered to 11 patients whose haemoglobin concentration was lower than 100
      g/l. The results from 10 patients were finally evaluated. During the first month
      all patients were given erythropoietin - 150 U/kg three times per week. Unless
      during the first month of treatment the haemoglobin concentration increased by 10
      g/l, the dose was doubled to 300 U/kg. In patients where the haemoglobin value
      had risen above 120 g/l, the authors assessed an individual maintenance dose. In
      case three-month erythropoietin treatment did not lead to an increase of
      haemoglobin by 20 g/l as compared with the baseline value, erythropoietin
      administration was discontinued. The haemoglobin concentration increased by 20
      g/l in a total of 8 (80%) of 10 evaluated patients. In all five patients where
      the haemoglobin concentration increased by 20 g/l during the first month, the
      endogenous erythropoietin concentration was less than 60 U/l. In another three
      patients the mentioned therapeutic response was recorded only during the 2nd or
      3rd month of treatment after the erythropoietin dose had been increased. These
      three patients had higher baseline concentrations of endogenous erythropoietin,
      100 to 350 U/l. During treatment no undesirable effects of erythropoietin were
      observed. Erythropoietin is a useful drug for anaemic patients with the diagnosis
      of multiple myeloma. According to the results of the authors work and data in the
      literature it is obvious that in patients with endogenous serum erythropoietin
      below 100 U/l a rapid riae of haemoglobin can be observed already during the
      first month. Patients with a higher baseline concentration of endogenous
      erythropoietin (100 to 500 U/l) respond less frequently to treatment and larger
      doses of erythropoietin must be administered. In patients with an erythropoietin
      value above 500 U/l there is a minimal probability that a response will be
      produced.

PMID- 8553597
TI  - [Hypercirculatory heart failure in a patient with plasmacytic leukemia].
AB  - High cardiac output failure/state (HCOF) is regular feature of some illnesses
      e.g. thiamine deficiency, hyperthyroidism, severe anemia, Paget's disease or
      arteriovenous fistulae. HCOF in multiple myeloma is reported quite rarely. 31
      year-old man was admitted because of fatigue, dyspnea and subfebrilities. Heart
      rate was 116/min, sinus rythm blood pressure 110/60 mmHg. Chest film showed
      cardiomegaly with sings of interstitial pulmonary edema, echocardiography mild
      dilatation of the left ventricle with hyperkinetic wall motion and small
      pericardial effusion. Hemoglobin was 104 g/l, leukocyte count 13.5 x 10(9)/l with
      30% of plasmatic cells. Serum protein electrophoresis demonstrated a monoclonal
      gammapathy, X ray studies of the skelet multiple osteolytic lesions. Diagnosis of
      plasmocytic leukemia-form of multiple myeloma was established and chemotherapy
      (vincristine + adriamycine + dexamethason) was started. Patient cardiac status
      deteriorated. Cardiac catheterisation demonstrated mean righ atrial pressure of
      25 mmHg, mean pulmonary artery pressure of 28 mmHg and pulmonary artery wedge
      pressure of 24 mmHg. Co was 20.0 l/min (C.I. 11.5 l/min/m2). In continuing of
      chemotherapy and symptomatic therapy for heart failure patients status gradually
      improved and complete remission of the myeloma and normalisation of cardiac
      parameters was achieved. Heart failure in multiple myeloma patients has been
      attributed to amyloidosis of myocardium, hyperviscosity syndrome, co-existing CAD
      or anthracycline toxicity. HCOF should be considered in patients with clinical
      evidence of heart failure and normal left ventricular function.

PMID- 8553598
TI  - [Subacute thrombosis of the abdominal aorta with suprarenal involvement and
      successful treatment with pharmacomechanical fibrinolysis].
AB  - In a 43-year-old patient with Ebstein's anomaly and a history of acute myocardial
      infarction by means of duplex ultrasonography and aortography the diagnosis of
      thrombotic occlusion of the a aorta was established, starting above the insertion
      of the renal arteries and reaching as far as the bifurcation of the aorta and the
      common iliac arteries. In the clinical picture dominated complete anuria with
      uraemia and marked hyperkaliaemia as a result of ischaemic affection of the
      extremities due to thrombosis of the aorta; at the onset of hospitalization also
      left ventricular failure with hyperhydration and later also signs of the
      hyperviscous syndrome. The latter developed after repeated haemofiltrations which
      led to a rise of the originally high haemoglobin and haemotocrit values a result
      of a righ-left shunt in Ebstein's anomaly. After improvement of the clinical
      condition local fibrinolytic treatment of the aortal thrombosis with urokinase
      (total dose 2,160,000 u. administered within 24 hours) was provided. The thrombus
      with a total length of 13.5 cm was dissolved except for a residual portion of 10
      mm located in the area of insertion of the right renal artery. After dissolution
      of the thrombus it proved possible to restore the blood flow into the left kidney
      a and lower extremities, but not into the right kidney because of the residual
      thrombus. Seventy-two hours after terminated fibrinolysis - and after 31 days of
      anuria - the diuresis was restored and after a polyuric stage normalization of
      mineral, urea levels was restored and the creatinine value was slightly above the
      upper normal range. Concurrently with fibrinolytic therapy angioplasty of the
      aorta was carried out and a stent was placed on the left iliac artery. The
      clinical condition of the patient was improving, the patient started to mount
      stairs. Death occurred suddenly and the cause was cardiac failure due to very
      serious congenital heart disease.

PMID- 8553599
TI  - [Unusual manifestations of dual atrioventricular nodal conduction].
AB  - In three case reports the unusual patterns of dual atrioventricular nodal
      conduction are shown - intermittent complete block in the fast pathway,
      Wenckebach-type block in the fast pathway, and parallel simultaneous conduction
      through both the nodal pathways with a double ventricular response. The
      importance of these phenomena consists at least in the differential diagnostics.

PMID- 8553600
TI  - [The importance of measuring pulmonary venous flow using doppler
      echocardiography].
AB  - Pulmonary venous flow can be evaluated by means of pulsed Doppler
      echocardiography during transthoracic or even better during transoesophageal
      examination. In the majority a three-peak spectral curve is recorded with the
      highest positive wave during ventricular systole, a lower positive wave during
      ventricular diastole and a negative wave during contraction of the left atrium.
      The author discusses some factors which have an impact on the pulmonary venous
      flow and which must be taken into account for its correct evaluation. With regard
      to clinical importance the author emphasizes in particular the change of venous
      pulmonary flow when the pulmonary pressure in the left ventricle rises. The
      latter may be used for its estimation. The pulmonary venous flow is a useful
      parameter also for quantification of significant mitral regurgitation and the
      differential diagnosis of restrictive cardiomyopathy and constrictive
      pericarditis. With regard to the simple assessment, rapidity of assessment and
      its predictive value it is suited for routine use in the majority of
      echocardiographic laboratories.

PMID- 8553601
TI  - [The role of echocardiography in the diagnosis of infectious endocarditis].
AB  - Echocardiography is irreplaceable in the diagnosis of infectious endocarditis. If
      in easily examined patients transthoracic examination suffices, in all other
      cases transoesophageal echocardiography is essential. It is important to
      emphasize the importance of searching carefully for complications, of assessment
      of the patient's risk and whether it is suitable to repeat the examination during
      treatment.

PMID- 8553602
TI  - [Osteoporosis. 1].
AB  - This article reviews the available data considering the question of pathogenesis
      and diagnostic of osteoporosis. Low bone mass can occur because there is
      insufficient bone deposited in the skeleton during growth, modelling, or because
      bone tissue is subsequently lost, remodelling. Peak bone mass is largely under
      genetic control, adequate nutrition during growth. Bone loss results from
      disturbance of bone remodelling, a continuous preventive maintenance programme in
      the adult skeleton. Bone remodelling is a quantum phenomenon that occurs in
      discrete units in four phases. Calciotropic hormones modulate the bone-cell
      production rate of cytokines and growth factors. Cytokines also locally mediate
      the effects of several hormones on bone cells. Disruption of the remodelling
      cycle at one of several points will lead to bone loss. Osteoporosis is a disease
      characterised by low bone mass per unit volume, microarchitectural deterioration
      of bone tissue leading to enhance bone fragility, and a consequent increase in
      fracture risk.

PMID- 8553603
TI  - [Surgical treatment of war injuries of the colon and rectum].
AB  - The results of retrospective analysis in the treatment of 155 wounded with
      colorectal lesions treated at the Military Medical Academy from July 1991 to
      December 1992 were presented. Primary surgical management was performed in 29
      (18.7%) wounded and the others were transported into this hospital for further
      treatment after primary surgical management in war hospitals in the combat zone.
      Colorectal lesion (42.6%) were mostly inflicted by bullets of various caliber and
      high kinetic energy. Time interval between the wounding and surgery was less than
      6 hours for 38.2% of wounded while 78.6% were operated within 12 hours. Multiple
      or combined colonic or rectal injuries were found in 91.6% of the wounded.
      Different surgical procedures were performed in accordance with the surgical war
      doctrine. Postoperative complications (colorectal cause) were found in 30 (19.3%)
      wounded. Reoperation was performed in 25 (16.1%) wounded and total mortality rate
      was 9.0% (14 wounded).

PMID- 8553604
TI  - [Mortality in esophageal cancer in Belgrade 1975-1989].
AB  - Mortality rate caused by esophageal cancer in Belgrade 1975-1989 was presented.
      During this fifteen-year period the average standardized mortality rate for
      esophageal cancer was 1.7 per 100,000 inhabitants. It was more than three times
      higher in males than in females (2.8:100,000 and 0.8:100,000). Mortality rates
      were age dependent and they were particularly higher in males over 45, so that
      the highest values were recorded in the oldest age group. Mortality rate for
      esophageal cancer during the period 1975-1989 was mildly ascending (y = 1.39 +
      0.04x). According to the standard mortality rate its value for esophageal cancer
      in Belgrade was within the frame of a low risk of dying due to this localization
      of digestive tract malignant neoplasms.

PMID- 8553605
TI  - [Acute renal insufficiency in poststreptococcal glomerulonephritis and its
      significance in evaluation of disease development in adults].
AB  - Importance of ARF occurring in the acute phase of PSGN in the disease evolution
      is still disputable because reported results are varying and even contradictory.
      Examination included 44 patients between 18 and 22 with the acute phase of PSGN.
      The serum creatinine levels over 124 mmol/l were found in 17 patients, while 27
      of them were without ARF in the acute phase of the disease. The aim of the study
      was, after diagnosing APSGN, to form groups of patients according to the ARF
      presence and to examine its influence in the initial phase of PSGN on its
      evolution and prognosis. On the basis of clinical parameters, pH changes, renal
      rebiopsy and ARF associated with the type of evolution, severity of clinical
      presentation and pH changes it was shown that occurrence of ARF in the acute
      phase of PSGN was of no significant importance for clinical presentation of the
      disease, but it could have some influence on the degree of morphologic changes
      found by renal rebiopsy.

PMID- 8553606
TI  - [Blast injuries of the intestines in abdominal injuries].
AB  - Intestinal blast injuries inflicted by explosive devices were found in 410
      wounded hospitalized at the Military Medical Academy. Primary blast perforations
      were found in 7 (1.7%) cases, and they were certain only in cases of the direct
      blast. Examination was directed toward the primary non-penetrating blast injuries
      of intestines not only because of their number 43 (11%), but also because they,
      if untreated, progressed into secondary perforations. Operative treatment of
      primary and secondary perforations was performed in accordance with the existing
      surgical war doctrine. Treatment of the intestinal wall hematoma as primary non
      perforating blast injury included surgical procedure and medication. Secondary
      perforations 11 (3%) developed in untreated primary non-perforating blast
      injuries of intestines. They were treated operatively except in two cases of
      enterocutaneous fistulas where conservative treatment was applied.

PMID- 8553607
TI  - [Serodiagnosis of toxoplasmosis using the IgM immunosorbent agglutination assay].
AB  - Sera of 155 patients were analyzed for toxoplasmosis, using ELISA test for IgM,
      ELISA test for IgG and ISAGA test for IgM. IgM-ISAGA was positive in 92.86% of
      acute cases, and in the group of patients with chronic infection in 6.36% of
      them. Comparing findings of ISAGA test for IgM with ELISA test for IgM obtained
      for all of 155 patients, ISAGA test's for IgM sensitivity was 93.3%, its
      specificity 95.3%, negative predictive value was 99.3%, and its positive
      predictive value was 66.6%.

PMID- 8553608
TI  - [Preparation and testing of buffers for fibrinogen].
AB  - Chloride-citrate-glucose solution was used in fibrinogen preparation for
      intravenous administration. Concentrated hydrochloric acid previously used for
      preparation of buffers for fibrinogen has been replaced by the diluted one
      enabling easier and more precise buffer pH regulation and faster fibrinogen
      dissolution. Procedure for spectrophotometric determination of the total citrate
      ion buffer system, sodium-citrate and citric acid was developed. Obtained results
      were within the prescribed limits but the ones obtained by officinal titration in
      non-aqueous medium were significantly decreased. Glucose was determined before
      sterilization by polymetric, and after sterilization by iodometric procedure.
      Chloride content was determined by coulometric titration and sodium content by
      flame photometry. Used analytic methods are simple and obtained results accurate
      and reproducible.

PMID- 8553609
TI  - [Molecular mechanisms in epilepsy and possibilities of their therapeutic
      correction].

PMID- 8553610
TI  - [Systemic vasculitis].

PMID- 8553611
TI  - [Social rehabilitation in psychiatric patients].

PMID- 8553612
TI  - [Transmission of viral infections through food].

PMID- 8553613
TI  - [Arterial embolism caused by penetration and migration of a bullet through the
      thoracic aorta].

PMID- 8553614
TI  - [Intraosseous schwannoma].

PMID- 8553615
TI  - [Nesidioblastosis of the pancreas as a cause of hyperinsulinemic hypoglycemia in
      adults].

PMID- 8553616
TI  - [Mediator systems in mechanisms of remission of experimental alcoholism and
      relapses of pathological craving for alcohol].

PMID- 8553617
TI  - [Ratio of neuromediator amino acids in a comparative analysis of the stress
      protective effects of delta-sleep inducing peptide and piracetam].
AB  - The GABAergic system was adequate altered after simultaneous use of delta
      sleeping peptide and piracetam in intact animals: gamma-butyric acid was
      accumulated unidirectionally by inhibiting brain glutamate decarboxylase
      activity. Administration of the peptide caused a slight decrease in the levels of
      aspartic acid, while piracetam contributed to a marked accumulation of the amino
      acid. The antistressor and adaptive effects of each drug were augmented if they
      were given simultaneously before acute emotional stress developed in the animals
      during one-hour hypokinesia; these effects were expressed as stabilized balance
      of inhibitory and excitatory neurotransmitter amino acids.

PMID- 8553619
TI  - [Cholesterol turnover in triglyceride transport and effect of probucol].

PMID- 8553618
TI  - [The alpha subunit of glycoprotein hormones as a biochemical marker of pituitary
      tumors].
AB  - Specific radioimmunoassay was developed for detection free glycoprotein hormone
      alpha-subunit (AS), by using AS prepared from highly purified human thyroid
      stimulating hormone (TSH). The assay showed that the basal content of free serum
      AS in the majority of 24 females with hormonally pituitary tumors secreting
      somatotropic hormone (STH, growth hormone), prolactin or either and in 24 females
      with unfunctioning pituitary tumors was significantly higher the mean one in 12
      females matched for the same age who had no endocrine diseases (control). The
      cultured cells of STH- and P-secreting tumors released excessive quantities of
      free AS along with STH and P into the medium with low glycoprotein holo-hormone
      levels. The content of AS changed little in 12 patients with non-functioning
      pituitary tumors despite the greatly increased serum TSH levels in response to
      the hypothalamic stimulator thyroid-releasing hormone. The findings suggest that
      free AS secreted into blood in excess despite hypothalamic control may be
      regarded as a biochemical marker of pituitary tumors.

PMID- 8553620
TI  - [Effect of the tetrapeptide tuftsin on activity of the monoaminergic system of
      the brain in experimental pathology].
AB  - Single administration of the regulating peptide tuftsin Thr- Lys-Pro-Arg (300
      micrograms/kg) was shown to affect the state of the transmitter systems in the
      brain of rats treated with the sedative drug haloperidol in a total dosage of 15
      mg/kg within 30 days. Haloperidol therapy caused reciprocal alterations in the
      activity of monoamine oxidases A and B, in the levels of dopamine, noradrenaline,
      serotonin, and 5-hydroxyindolyl acetic acid, as well as a decrease in the rate of
      depolarization-dependent Ca(2+)-capture in the synaptosomes of the rat brain
      cortex and neostriatum (N. caudatus); under these conditions tuftsin normalized
      the parameters studied to a certain extent, which was more pronounced in N.
      caudatus. The peptide appeared to activate synaptic transfer in the dopaminergic
      nerve endings and to contribute to balance restoration in the neurotransmitter
      systems (particularly in the neostriatum) impaired by abnormalities.

PMID- 8553621
TI  - [Status of bioenergetic processes in brain tissue in dynamics of acute cranio
      cerebral trauma].
AB  - Acute brain injury was simulated in rat experiments. Great changes were revealed
      in carbohydrate and energy metabolism over the course of the posttraumatic
      period. The changes are the most pronounced 1 day after injury and they showed
      deep energy deficiency in brain tissue and precede the development of and greatly
      contribute to the pathogenesis of many posttraumatic disorders, including brain
      edema-swelling.

PMID- 8553622
TI  - [Relationship of free and conjugated forms of catecholamines in depressive
      disorders in psychopathic personalities].
AB  - The study was undertaken to examine the content of free and conjugated forms of
      norepinephrine, dopamine, epinephrine in the daily urine and blood plasma of
      psychopathic patients during varying severity depressive disorders. To isolate
      the conjugated forms, hot acid hydrolysis was applied, catecholamines were
      measured by the procedures based on high performance liquid chromatography with
      electrochemical detection. Patients with the most marked clinical signs of
      depressions were found to have the most profound urinary and blood shortage of
      free forms of dopamine and norepinephrine, as compared with the controls, which
      was associated with the most intensive conjugation of these catecholamines. Thus,
      it may be supposed that disturbances of the catecholamine conjugation systems are
      one of the neurochemical mechanisms underlying the development of affective
      disorders.

PMID- 8553623
TI  - [Disruption of central regulation of reproductive function under the effect of
      unfavorable environmental factors].
AB  - Rat experiments have established that early unfavourable environmental influences
      cause a non-specific response of the central link of reproductive function
      regulation as manifested by the impaired circadian rhythm of gonado releasing
      hormone through the vascular organ of the lamina terminalis. It is suggested that
      this is induced by changes in prolactin production. Under unfavourable
      environmental influences there were insidious changes in the neuroendocrine
      regulation of reproductive function, which emerge with the involvement of
      additional damaging factors or functional tests. They are easily reversible and
      functional, but they may be regarded as the first signs of reproductive
      dysfunction.

PMID- 8553624
TI  - [Effect of estradiol on the rat brain synaptosomal phosphoinositide composition].
AB  - The in vivo action of estradiol was shown to cause changes both in the total
      amount of phosphoinsitides and their individual fractions of rat synaptosomes.
      The maximum elevated levels of phosphoinositides was revealed on 1-hour exposure
      to the hormone. It is suggested the redistribution of phosphoinositides at the
      primary stage (1 hour postinjection) of exposure may rely on the initiation and
      functioning of the phosphoinositide mechanism, the ratio of triphosphoinositide
      to monophosphoinositide may be a peculiar indicator of the status of synaptosomal
      membranes for the functioning of this regulatory system.

PMID- 8553625
TI  - [Effect of captopril and reserpine on the activity of certain neuropeptide
      metabolism enzymes].
AB  - Chronic consumption of the highly specific angiotension-converting enzyme
      inhibitor captopril was found to decrease the activity of the enzyme in the rat
      hypothalamus and striatum and to enhance it in the pituitary and blood serum. The
      agent also increased the activity of carboxypeptidase N in the serum and that of
      carboxypeptidase H in the pituitary. Reserpine, a catecholaminergic blocking
      agent, reduces the pituitary and serum activities of angiotensin-converting
      enzyme and activates soluble carboxypeptidase H in the pituitary and striatum and
      membrane-bound carboxypeptidase in the hypothalamus and striatum. Possible
      mechanisms of action of captopril and reserpine on the activity of the enzymes in
      question, as well as a contribution of these enzymes to their antihypertensive
      effect are discussed in the paper.

PMID- 8553626
TI  - [Dynamics of luminol-dependent chemiluminescence in rat whole blood at different
      oxygen concentrations].
AB  - Chemiluminescence analysis was used to examine the yeast cell-activation of rat
      whole blood neutrophilic leukocytes in rats after their pre-exposure to 3-hour
      hypoxia (9,000 m above sea level) and two-hour hyperoxia (0.3 MPa), as well as
      their resultant effects. The hypoxia was found to cause a significant (42%)
      reduction in the length of the latent period, suggesting that it activates the
      phagocytic activity of neutrophilic leukocytes. At the same time hyperoxia leads
      to a delayed response of competent cells to yeast cell stimulation. On subsequent
      exposure to hypoxia and hyperoxia, drastic inhibition of drastic cellular
      activation occurred, which manifested itself by a 62% increase in the length of
      the latent period and by a 38% rise in the appearance time of luminescence peak.
      Thus, the findings suggest that it is essential to bear in mind the fact that
      phagocytosis can decrease if oxygen is overdosed during hyperbaric oxygenation
      and in hypoxic states.

PMID- 8553627
TI  - [Effect of thiamine and riboflavin derivatives on the activity of xenobiotic
      metabolizing enzyme and on the pharmacologic effect of analgesics].
AB  - Riboflavin deficiency decreases the activity of rat hepatic microsomal enzymes,
      addition of riboflavin and flavin mononucleotide stimulates their activity. At
      the same time thiamine deficiency induces xenobiotic metabolic enzymes and
      excessive addition of thiamine, thiamine diphosphate in particular, suppresses
      their activity. Flavin mononucleotide and thiamine diphosphate considerably
      modify the pharmacological effect of the agents which are actively metabolized by
      the hepatic microsomal system. Thiamine diphosphate enhances the pharmacological
      activities of orthophen, indomethacin, and tramal while flavin mononucleotide
      slightly diminishes them.

PMID- 8553628
TI  - [Regulation by thyroxine of the functional activity of liver and brain
      mitochondria in developing rats and participation of cytoplasmic protein factors
      in this process].
AB  - The physiological (10(-8)M) concentration of free thyroxine (T4) and specific
      thyroxine-binding protein (a thyroxine action modulator-MDT4) was studied for its
      effect on protein synthesis, respiration and oxidative phosphorylation of
      mitochondria in the liver and brain of developing rats. Free T4 was demonstrated
      to affect the studied parameters in the mitochondria of the liver and brain of
      the developing rats very rarely, if at all. In the liver MDT4 stimulated
      mitochondrial functional activity during all the studied developmental periods
      whereas in the brain mitochondria the modulator stimulated the synthesis of
      proteins and phosphorylating respiration only in early postnatal life. In the
      following periods of development there was a modulator-induced decrease in
      protein incorporation of labelled leucine, respiration, and conjugation strength
      of brain mitochondria. The findings suggest that thyroidal hormones ambiguously
      regulate the functional status of mitochondria in the liver and brain of the
      developing rats and the specific hormone-binding protein MDT4 takes an active
      part in this regulation.

PMID- 8553629
TI  - [Use of an activated chemiluminescence method for studying the pharmacologic
      properties of medicinal substances].
AB  - When given to non-inbred male rats during 1, 2, and 3 months, aqueous extract
      from the above-ground Padus Grajana maxim parts was tested for its effects on the
      parameters of chemiluminescence-activated rat serum. The tested agent was found
      to increase he rate of rapid and slow chemiluminescence flashes. The level of
      steady-state glow considerably declined after the agent was given for a month;
      however, its longer use increased the steady-state chemiluminiscence and by the
      end of the 3rd month it was equal to that of control animals. Whether the
      activated chemiluminescence technique can be used to evaluate the effect of
      biologically active substances on cell structures, to refine some aspects of the
      mechanism of action of drugs is discussed on in terms of the findings.

PMID- 8553630
TI  - [Analysis of cytogenetic activity of food dyes].
AB  - The cytogenetic activity of food dyes was examined in the experiments on male
      C57B1/6 mice which were orally given during 5 days the following daily doses:
      Tartrasine (E102), 0.5 and 5.0 mg/kg; Indigo carmine (E132), 1.4 and 14 mg/kg;
      Canset yellow (E110), 0.17 and 1.7 mg/kg; Cochenillerot A (E124), 0.63 and
      6.3mg/kg; Azorubin (E122), 1 and 10 mg/kg and Patentblau V (E131), 0.08 and 0.8
      mg/kg. Five hundred metaphase slides each were analyzed in the control and
      experimental test series. The findings may conclude that the dyes tested within
      the above dose ranges do not induce any increase in the level of cells with
      chromosomal damages in the inbred animals.

PMID- 8553631
TI  - [Characteristics of lipid metabolism in workers of the petrochemical industry].
AB  - The serum levels of lipids and lipoproteins were measured in 501 workers engaged
      in petrochemical industry and 100 control men. Highly elevated cholesterolemia,
      triglycerolemia with decreased serum phospholipid and lipoprotein concentrations
      are strictly characteristic in petrochemical industrial workers. There was a
      clear-cut relation of these changes to the nature of the type of production, age,
      especially to the length of service in petrochemical industry. The findings
      suggest that the nature of a chemical agent, the time of a lesion might play a
      significant role in the development of an atherosclerotic process in workers
      engaged in petrochemical industry.

PMID- 8553632
TI  - [Stress-limiting effect of zantac in duodenal ulcer bleeding].
AB  - Two randomized groups of patients with ulcerative gastroduodenal hemorrhage were
      studied. One group of patients with bleeding-accompanied ulcerative disease of
      the stomach (n = 11) and the duodenum (n = 22) received the routine therapy,
      another group, including those of the same diseases (n = 9 and n = 22,
      respectively) had additionally the histamine H2-receptor blocking agent zontac by
      the following schedule: intravenously, 50 mg thrice a day within the first 3
      days, and orally, 150-mg tablets twice a day within the following 3 weeks. Donors
      (n = 20) served as a control group for the zontac-treated and untreated patients.
      The stress-limiting effect of zontac was evaluated by the physicochemical
      parameters of corticosteroid-binding globulin, serum cortisole and insulin
      concentrations which were measured on days 1, 3, 7, and 14 following the first
      hemorrhage. In the zontac-treated group, the association constant of the blood
      cortisole-corticosteroid-binding globulin increased, while the dissociation
      constant decreased. At the same time the absolute and relative number of sites
      for binding of cortisole by means of corticosteroid-binding globulin also dropped
      to the values seen in the group of donors. Zontac caused a reduction in the
      cortisole/insulin ratio. This all suggests that zontac produces its stress
      limiting effect in patients with ulcerative gastroduodenal hemorrhage. Zontac
      therapy decreased the need for surgical arrest of bleeding by 50% and the average
      day/bed.

PMID- 8553633
TI  - [Search for an endogenous ligand for sigma receptors].
AB  - Whether there is an endogenous ligand for sigma receptors remains unknown. A
      total lipid fraction was isolated from the porcine liver, which was then
      subjected to chromatographic separation, yielding nine chromatographic fractions
      eluated at various chloroform/methanol ratios: each fraction was tested for its
      capacity of inhibiting the binding of (+)-[3H]SKF 10047 to hepatic sigma
      receptors. The chromatographic fraction 7 + 7A (eluated at chloroform/methanol
      ratios of 60:40-10:90) which consisted mainly of phospholipids was found to have
      the highest activity. However, a complex analysis of this fraction revealed no
      relationship of its sigma-inhibiting activity to phospholipids. It is suggested
      that the non-competitive inhibition of (+)-[3H]SKF 10047 binding by the isolated
      active fraction is due to its presence of an endogenous ligand which, interacting
      with sigma-2 receptor, allosterically inhibits the binding of the labelled (+)
      benzomorphan.

PMID- 8553634
TI  - Physician-patient communication in managed care.
AB  - The quality of physician-patient communication affects important health care
      outcomes. Managed care presents a number of challenges to physician-patient
      communication, including shorter visits, decreased continuity, and lower levels
      of trust. Good communication skills can help physicians create and maintain
      healthy relationships with patients in the face of these challenges. We describe
      5 communication dilemmas that are common in managed care and review possible
      solutions suggested by recent literature on physician-patient communication. We
      also describe ways that managed care plans can promote more effective
      communication between physicians and patients.

PMID- 8553635
TI  - Primary care physicians in underserved areas. Family physicians dominate.
AB  - Using the definitions of "medically underserved areas" developed by the
      California Health Manpower Policy Commission and data on physician location
      derived from a survey of California physicians applying for licensure or
      relicensure between 1984 and 1986, we examined the extent to which different
      kinds of primary care physicians located in underserved areas. Among physicians
      completing postgraduate medical education after 1974, board-certified family
      physicians were 3 times more likely to locate in medically underserved rural
      communities than were other primary care physicians. Non-board-certified family
      and general physicians were 1.6 times more likely than other non-board-certified
      primary care physicians to locate in rural underserved areas. Family and general
      practice physicians also showed a slightly greater likelihood than other primary
      care physicians of being located in urban underserved areas.

PMID- 8553636
TI  - A homeless shelter medical clinic organized and staffed by family practice
      residents.
AB  - A medical clinic was organized in a homeless shelter to help address the health
      care needs of the homeless population in a small California city. A second-year
      family practice resident, together with two community nurses and a local family
      practitioner, organized and staffed the clinic. After the first winter of
      operation, family practice residents on their own initiative took over the
      management of the clinic. The clinic serves the needs of the clients in the
      homeless shelter, provides family practice residents an opportunity to work
      independently of the residency program, and offers a sought-after experience in
      caring for the underserved.

PMID- 8553637
TI  - What physicians should know about Africanized honeybees.
AB  - The Africanized honeybee, popularly known as the "killer bee," is already well
      established in Texas and has recently entered California and Arizona. As the
      Africanized honeybee spreads in North America, the medical community must become
      aware of the problems associated with this insect and ensure that sting
      emergencies can be handled quickly and appropriately. The major differences
      between Africanized and European honeybees are that the former are more
      irritable, they swarm more readily and frequently, they defend their hives more
      vehemently, and they sting more collectively. It is not the composition nor the
      volume of an individual bee's venom, but rather the cumulative dose of multiple
      stings that accounts for the morbidity and mortality associated with Africanized
      honeybee-sting incidents. Even nonallergic persons are susceptible to the toxic
      effects of these large combined venom loads. Africanized honeybee-sting victims
      are treated the same as victims of European honeybee stings. Authorities will
      prepare for the bees' arrival by expanding public awareness, teaching risk
      avoidance behavior, providing for the removal of troublesome hives, and
      developing sting treatment protocols that can be initiated rapidly in the field
      or emergency departments. Health care professionals should participate in the
      educational efforts and in the development of needed emergency response protocols
      so that the effects of the Africanized honeybee will be merely a nuisance rather
      than a plague.

PMID- 8553638
TI  - Poisonous snakebite in Utah.
AB  - A retrospective study was done of poisonous snakebite in Utah to determine the
      current epidemiology and scope of treatment, reviewing emergency department logs
      and other sources statewide for a 69-month period. Of 61 cases of poisonous
      snakebite identified, 13 occurred in snake hobbyists or venom laboratory
      personnel and were considered nonaccidental, and 48 were inflicted by native
      noncaptive snakes. These bites were considered accidental, and all were presumed
      to be from rattlesnakes. Nearly three fourths of the victims were male, ranging
      in age from 2 to 56 years (mean, 22 years). Most accidental bites occurred in
      areas of high human populations, during the summer months, in the afternoon or
      evening hours, and during recreational activities. Of the 48 bites, 11 (23%) were
      provoked. Two thirds of bites were on the upper extremities, and a third were on
      the lower extremities. More than half of the victims had no first-aid treatment
      recorded. Of those who did receive first aid, many were subjected to possibly
      harmful treatments, including tourniquets and ice application. The median time to
      a hospital was 68 minutes, with a range of 15 to 440 minutes. Swelling and
      discoloration were the most common signs and pain and paresthesia the most common
      symptoms. Half the bites resulted in minimal or no envenomation, 17 (35%)
      produced moderate envenomation, and 6 (12%) severe envenomation. Most patients
      with moderate or severe envenomation received antivenin, but the dosages given
      were usually less than recommended dosages. Five patients received surgical
      treatment based on clinical findings. One child died in a snake-handling
      incident. Long-term morbidity was unknown due to lack of follow-up. The Utah
      Poison Control Center was poorly utilized as a reporting and informational
      resource.

PMID- 8553639
TI  - Syphilis. A tale of twisted treponemes.
AB  - Despite the widespread availability of effective treatment, the incidence of
      primary and secondary syphilis in the United States is on the rise. In addition,
      syphilis is occurring in a substantial number of patients infected with the human
      immunodeficiency virus (HIV), thus adding to the complexities of diagnosis and
      treatment. Primary syphilis represents a disseminated infection, often
      accompanied by abnormalities of the cerebrospinal fluid, that may pass
      unrecognized and progress to the myriad manifestations of secondary syphilis. The
      diagnosis of syphilis in patients with mucosal or skin lesions may be made by
      darkfield examination; once lesions have resolved, serologic tests are required.
      Patients with latent syphilis may have asymptomatic neurosyphilis and risk
      progression to tertiary disease. The diagnosis of asymptomatic neurosyphilis is
      necessary to determine the optimal treatment of patients with latent disease. The
      diagnosis of active neurosyphilis generally requires an inflammatory
      cerebrospinal fluid profile and a reactive cerebrospinal fluid VDRL test.
      Syphilis is common in HIV-infected patients, who may have an altered antibody
      response to infection and an apparent increased incidence of neurologic
      complications. The preferred treatment at all stages is penicillin, which is also
      the only recommended therapy for neurosyphilis. The optimal treatment of syphilis
      in HIV-infected patients is unknown.

PMID- 8553640
TI  - Health care in correctional facilities.
AB  - More than 1.3 million adults are in correctional facilities, including jails and
      federal and state prisons, in the United States. Health care of the inmates is an
      integral component of correctional management. Health services in correctional
      facilities underwent dramatic improvements during the 1970s. Public policy trends
      beginning in the early 1980s substantially affected the demographics and health
      status of jail and prison populations and threatened earlier gains in the health
      care of inmates. Correctional health services are seldom considered in
      discussions about health policy and health care reform.

PMID- 8553641
TI  - Orthopedic implications of tuberculosis.

PMID- 8553642
TI  - Bone graft substitutes.

PMID- 8553643
TI  - Arthroscopic subacromial decompression for the shoulder impingement syndrome.

PMID- 8553644
TI  - Anterior cruciate ligament repair in children.

PMID- 8553645
TI  - The Ilizarov method.

PMID- 8553646
TI  - Necrotizing soft tissue infections.

PMID- 8553647
TI  - Women's shoe wear and foot disorders.

PMID- 8553648
TI  - Treatment of fractures of the femur in children and adolescents.

PMID- 8553649
TI  - Surgical indications for spinal instrumentation in degenerative diseases.

PMID- 8553650
TI  - Ingestion of poison hemlock (Conium maculatum).

PMID- 8553651
TI  - Multiple organ dysfunction caused by parvovirus B19.

PMID- 8553652
TI  - Hypocalcemia due to avid calcium uptake by osteoblastic metastases of prostate
      cancer.

PMID- 8553655
TI  - [Mites (Cheliceromorpha, Arachnida: Acari) remarks on phylogeny and evolution].

PMID- 8553654
TI  - Modern syphilis--still a shadow on the land.

PMID- 8553656
TI  - [Arachnids as risk factors in occupational exposure].
AB  - Arachnids pose two types of occupational hazard, mainly affecting agricultural
      and forestry workers. The first type is associated with bites of ticks, mites and
      spiders resulting in a local skin inflammation, systemic symptoms due to
      intoxication and the transmission of pathogenic viruses or bacteria, mainly
      caused by tick vectors. The second type is associated with the exposure to
      storage mites which cause asthma and rhinoconjunctivitis in farmers and grain
      workers.

PMID- 8553657
TI  - Present state of research on ticks (Ixodoidea) in the Czech Republic.
AB  - Tick research in the Czech Republic started developing rapidly after World War II
      and was directed to the faunistics and taxonomy, biology, ecology and behaviour,
      physiology and genetics, disease transmission, host-parasite relationships and
      control. Altogether 15 tick species were reported from the territory of the Czech
      Republic. Most studies in biology, ecology and virus transmission were dedicated
      to Ixodes ricinus, but biology and ecology of Dermacentor reticulatus, I. laguri
      and I. hexagonus were also studied. Many studies were done on argasid ticks,
      mostly on pheromonal communication of Argas persicus and immunology of feeding of
      A. polonicus. Population variability of both these species was also studied. The
      present research on ticks is mostly directed to study of interaction among hosts,
      ticks and pathogens on the humoral, cellular and molecular level.

PMID- 8553653
TI  - Osteoarthritis. A continuing challenge.
AB  - Osteoarthritis is a disorder of cartilage that affects almost 85% of the
      population by age 75. A lack of rigorous clinical and radiographic criteria for
      defining the disorder makes precise determination of its prevalence impossible.
      The process of wear and tear explains many manifestations of osteoarthritis, but
      it does not account for some of the clinical findings or the biochemical changes
      in osteoarthritic cartilage. Thus, other factors such as heredity, hormones, and
      diet may play a role. Treatment consists of teaching patients about their
      disease, alleviating pain, and preserving joint function. Nonsteroidal anti
      inflammatory drugs may be no more effective than simple analgesics in relieving
      the pain of this disorder. Moreover, some nonsteroidal anti-inflammatory drugs
      can adversely affect cartilage metabolism, and most are possibly dangerous in
      elderly patients. Drugs that inhibit the production or activity of chondrolytic
      enzymes can slow the degeneration of cartilage in some animals, but their effects
      on humans with osteoarthritis are unproved. The surgical repair of severely
      damaged joints can have gratifying results.

PMID- 8553658
TI  - [Tick fauna (Acari: Ixodida) in Poland].
AB  - 20 valid species of Ixodida (3 Argasidae and 17 Ixodidae) are actually recognized
      as permanently existing in Poland. Cases of transferring 5 other Ixodidae were
      also recorded. Argasidae are nests- and burrows-dwelling species having multi
      host development cycle, they are mainly synanthropic and semisynanthropic,
      nocturnal active, with the peak seasonal activity in the middle of summer. The
      most of Polish Ixodidae species are burrows- and nests-dwelling parasites, more
      common species are out of nest-dwelling, having three-host development cycle;
      they are basically polyxenic, active during the warm season of year, normally
      with two peaks of activity--in spring and at the end of summer, beginning of
      autumn; in most cases live in forests.

PMID- 8553659
TI  - [Teratologic changes complicating taxonomical studies of ticks (Acari: Ixodida)].
AB  - Various kinds of morphological anomalies, i.e. general (the changes in the shape
      and the asymmetry of body, the duplication of body, the nanism, the gigantism and
      the gynandromorphism), and local (oligomely, atrophy, polimely, heterosymely,
      symely, schistomely, ectomely, heteromorphose, disturbances in the structure of
      leg segments, cyclopy) occur in Ixodida. The anomalies within taxonomically
      important structures make the determination of tick species difficult or even
      impossible. Therefore, the anomalies deforming systematic features of different
      instars from Argasidae and Ixodidae families were first of all taken into
      account.

PMID- 8553660
TI  - [The role of ticks occurring in Poland in the epidemiology of transmitted
      diseases].
AB  - This paper is a comprehensive presentation of the role of ticks, especially those
      occurring in Poland, in the epidemiology of arthropod-borne diseases. Following
      paragraphs review briefly principal diseases of viral, rickettsial and bacterial
      etiology with emphasis on natural circulation of pathogens between ticks serving
      as vectors and various vertebrates which function as tick hosts and pathogen
      reservoires. The vertical circulation of pathogens within the ticks population as
      well as modes of transmission of viruses, rickettsiae and bacteria by ticks to
      man are also outlined.

PMID- 8553661
TI  - [Ticks (Ixodidae) in zoonotic propagation of piroplasma Babesia micorti and
      Babesia divergens].
AB  - Recent advance in the knowledge of the role of Ixodidae in the epidemiology of
      human piroplasmosis is reviewed, with special emphasis on Babesia species which
      cause diseases in man. The problem in Europe came to medical attention since 20
      cases have been reported, and most of them due to B. divergens. However, contrary
      to other European countries, the zoonotic reservoir of Babesia spp. in Poland is
      unknown and further research is required to elucidate the importance of Ixodidae
      in the transmission of piroplasms.

PMID- 8553662
TI  - Ecology of Ixodes ricinus immatures on Apodemus agrarius (Muridae) in the lowland
      ecosystems conditions.
AB  - Ecology of Ixodes ricinus collected on black-striped field mouse (Apodemus
      agrarius) was studied in the lowland ecosystems. During the study period (1986
      1991), 1483 specimens of A. agrarius were examined in southern Slovakia and 1319
      larvae and nymphs were collected from hosts. The seasonal pattern--bimodal (peak
      in spring and autumn)--was distinct for larvae. Both prevalence and abundance of
      tick infestation of A. agrarius by nymphs were low. Prevailing material of nymphs
      was collected from May (pooled data from all years) on mature hosts. There were
      significantly higher infestation in mature males than in females as well as
      significantly higher tick infestation of mature hosts than immature ones. Higher
      abundance of tick infestation of A. agrarius in fields is probably influenced by
      great spatial mobility of hosts and by import of ticks from landscape verdure.

PMID- 8553663
TI  - Present state of research on house dust mites (Pyroglyphidae) in the Czech
      Republic.
AB  - Systematic research on house dust mites in the Czech Republic started in the
      early seventies, when mite fauna of human dwellings and distribution of
      pyroglyphid mites were studied. Special attention was paid to old-age-pensioners'
      homes and children's sanatoria. Pyroglyphidae were found also in the city air and
      in the dust of city pavements, especially in localities with high occurrence of
      domestic pigeons. While D. pteronyssinus and D. farinae mostly occurred in
      permanently inhabited flats, Euroglyphus maynei prevailed in recreation houses
      and some hospitals. Autumn increase of population density occurred in both, D.
      pteronyssinus and D. farinae populations, however, the number of protonymphs was
      remarkable higher than that of other developmental stage in D. farinae
      population. Special rearing technique was developed for the mass-culture of mites
      and a Czechoslovak patent was assigned to the technology of allergen preparation
      for the diagnostics and the desensibilization of patients with house-dust
      allergies.

PMID- 8553664
TI  - [Fauna and biology of the Pyroglyphidae of Poland].
AB  - 5 valid species of pyroglyphid mites are actually known in Polish fauna. It
      should be stressed that the knowledge of their occurrence in house-dust, bird
      nests and other habitats is still poor. The most common pyroglyphid house-dust
      mites, Dermatophagoides pteronyssinus, D. farinae and Euroglyphus maynei, were
      found in samples of dust from houses (Warszawa, Bydgoszcz, Upper Silesia),
      hospitals (Katowice, Sosnowiec), libraries (Sosnowiec) and port buildings
      (Gdynia). The both species of the genus Dermatophagoides were also found in house
      dust samples in Poznan and Poznan vicinity, whereas E. maynei and D.
      pteronyssinus--occasionally in stored herbs in Grudziadz. Moreover, Gymnoglyphus
      longior was reported from house-dust (Tarnowskie Gory, Upper Silesia), debris
      from a byre in Lesko and from barn litter in Solarnia near Lubliniec, while
      Hirstia passericola was found in byre debris in Lesko. It seems that D.
      pteronyssinus and D. farinae are common in house-dust all over the country. The
      following pyroglyphid mite species--D. pteronyssinus, H. passericola, G. longior-
      are reported from nests of birds in Poland.

PMID- 8553665
TI  - [Allergy to house dust mites].
AB  - There are presented the etiology and pathogenesis of house dust and house dust
      mite allergy. The house dust mite ecology, physicochemic and immunochemic
      properties of house dust mite allergens, methods of quantitating exposure to
      these allergens; the relationship between level of exposure, sensitization and
      disease, likewise avoidense measures for mite allergens in houses are described.

PMID- 8553666
TI  - Cytoreduction and sequential resection for surgically verified unresectable
      hepatocellular carcinoma: evaluation with analysis of 72 patients.
AB  - The poor prognosis of hepatocellular carcinoma (HCC) was partly a result of the
      majority of unresectable HCCs in clinical patients. Fortunately, with the
      progress of regional cancer therapies and multimodality treatment, some of the
      localized unresectable HCCs were converted to resectable ones. During the period
      1960-1994, 72 of the 663 patients with surgically verified unresectable HCCs have
      been converted to resectable. Successful cytoreduction with median diameter
      reduced from 10 cm to 5 cm was mainly a result of the triple or double
      combination treatment with hepatic artery ligation, hepatic artery cannulation
      with infusion, radioimmunotherapy, and fractionated regional radiotherapy. The
      interval between the first operation and the sequential resection was 5 months.
      The operative mortality was 1.4% for sequential resection, and the 5-year
      survival was 62.1%. Analysis of factor influencing sequential resection rate
      revealed HCCs that were single nodule, well encapsulated, situated at right lobe
      or hepatic hilum, associated with micronodular cirrhosis, and treated with triple
      or double combination modalities had higher sequential resection rate as compared
      to their counterparts. Analysis of factors influencing survival after sequential
      resection revealed that HCCs with a solitary tumor confined in one lobe, without
      tumor embolus, and without residual cancer in specimen of sequential resection,
      had longer survival. It is suggested that localized unresectable, solitary, well
      encapsulated, right lobe or hilar HCC, associated with micronodular cirrhosis,
      will be good candidates for cytoreduction and sequential resection; and HCCs with
      unilateral involvement, without tumor embolus, and with complete necrosis of
      tumor after multimodality treatment favored better prognosis.

PMID- 8553667
TI  - Conversion of unresectable to resectable liver cancer: an approach and follow-up
      study.
AB  - In the last decade, significant improvement has been achieved in the treatment of
      hepatocellular cancer by combining therapies from different disciplines, and
      using effective biologic response modifiers to improve response to existing
      therapy. While operative resection remains the only curative modality, a select
      group of patients with unresectable fibrolamellar or nodular variant, can be
      converted from unresectable status to resectable by combining chemotherapy and
      radiotherapy. We reviewed the recent experience with intra-arterial
      chemotherapies and use of external beam radiotherapy and isotopic immunoglobulin
      directed radiotherapy in the treatment of unresectable hepatocellular cancer.
      While significant tumor response can be achieved with these therapies they are
      short-lived, and long-term survival is poor. When combined with operative
      resection, however, a significant survival advantage is achieved. The expected
      survival of the unresectable patient is then altered from 18 to 24 months for
      chemotherapy or radiation alone, or when used in combination, to 44 months for
      patients converted to resectable status. We conclude that the need for more
      effective chemotherapy is imperative, and the major role for chemotherapy or
      radiotherapy in hepatocellular cancer is to convert an unresectable patient to
      resectable status.

PMID- 8553668
TI  - Transcatheter arterial chemoembolization (TACE) in the treatment of unresectable
      liver cancer.
AB  - Basis, techniques, and recent strategies and results of interventional treatments
      for hepatoma were reviewed. The basic experimental researches indispensable to
      justify clinical technique and dosage have been accomplished. A total of 1310
      unresectable cases underwent transcatheter arterial chemoembolization (TACE)
      and/or related therapies. The related therapies are several modified or
      strengthened TACE such as Lipiodol-TACE and subsegmental TACE. The therapies for
      unembolizable cases are balloon occluded arterial infusion, Lipiodol-SMANCS
      infusion and percutaneous direct injection chemotherapy, that reinforces the
      effect of TACE. As for the resectable cases, postoperative TACE was proved to be
      beneficial because it increased survival rates; however, preoperative TACE was
      not beneficial. The TACE and related interventional radiologic therapies for the
      hepatoma can be an equal or superior therapy by virtue of targeting chemotherapy.

PMID- 8553669
TI  - Intralesional ethanol in the treatment of unresectable liver cancer.
AB  - Percutaneous ethanol injection (PEI) under ultrasonography guidance has been
      widely tried in not advanced hepatocellular carcinoma (HCC). Ten years after the
      introduction of PEI, some conclusions of its indications can be drawn. In our
      series, 210 cirrhotic patients were treated; 141 with multisession PEI in an
      outpatient clinic, 57 with "single session" PEI under general anesthesia, and 12
      with both. The 1-, 3-, and 5-year survival rates (by Kaplan-Meier method) were
      953%, 65%, and 41% for Child class A patients with single HCC < or = 5 cm, and
      88%, 47%, and 33% for patients with multiple HCC up to five lesions < or = 5 cm.
      In these patients the local recurrence rate was 15% and the new lesion rate at
      the 5-year follow-up was 74%. One death due to hemorrhage from esophageal varices
      in a Child class C patient treated by single session PEI occurred. The large
      number of cirrhotic patients demand for effective, safe, repeatable, low-cost
      treatment that can be offered at many centers. PEI meets all these requirements.
      PEI is proposed as the treatment of choice for the mentioned patients, excluding
      candidates for liver transplantation and surgical resection according to the
      predictive adverse factors currently in use. "Single session" technique widened
      the indications of traditional PEI to larger lesions.

PMID- 8553670
TI  - Role of liver transplantation in the treatment of unresectable liver cancer.
AB  - Resection remains the treatment of choice in liver cancer. In order to avoid
      liver transplantation in conventionally unresectable tumors ex-situ ("bench"
      procedure), in-situ and ante-situm resection technique should be preferred
      whenever feasible. Despite the deficiency of donor organs, a single center
      experience with 198 patients reveals that liver transplantation continues its
      role as a therapeutic option for selected patients. At present "favorable"
      indications for transplantation are International Union against Cancer (UICC) -
      stage II hepatocellular carcinoma as well as the subtype fibrolamellar carcinoma,
      uncommon tumors such as epitheloid hemangioendothelioma, hepatoblastoma, and
      liver metastases from neuroendocrine tumors. Due to unsatisfying results,
      intrahepatic bile duct-, stage III and IV hepatocellular carcinoma,
      hemangiosarcoma, and liver metastases from nonendocrine primaries should be
      excluded from liver transplantation alone. For these advanced tumors, especially
      in cases of extrahepatic involvement, a combination of liver transplantation and
      multivisceral resection has been proven feasible. However, a significant
      improvement in patient survival may only be expected only by currently
      investigated multimodality treatment protocols which will require further
      randomized studies.

PMID- 8553671
TI  - Conversion of unresectable to resectable hepatoblastoma and long-term follow-up
      study.
AB  - In children with hepatoblastoma, cure or a prolonged disease-free interval can
      only be accomplished with surgical resection of the primary tumor. Less than 50%
      of children with hepatoblastoma are felt to have resectable tumors at the time of
      diagnosis. Clinical studies have recently focused on the hypothesis that adjuvant
      chemotherapy can convert the unresectable tumor to a tumor that can be resected.
      Short-term outcomes for patients treated with adjuvant chemotherapy and
      subsequent resection are nearly equal to those patients treated with initial
      resection followed by chemotherapy. This study is a review of the current
      literature of the chemotherapeutic conversion of unresectable hepatoblastoma and
      an update on the long-term follow-up of some of these patients.

PMID- 8553672
TI  - Resection of stage III non-small cell lung cancer following induction therapy.
AB  - Approximately 25%-30% of all patients with non-small cell lung cancer (NSCLC)
      present with stage III tumors. Except for specific subsets, these tumors are not
      usually amenable to complete surgical resection and are associated with a 5-year
      survival of 10% or less. Because patients with stage III NSCLC die of distant
      metastases, recent efforts to improve the prognosis of these tumors have focused
      on neoadjuvant therapy using chemotherapy or chemoradiotherapy as induction
      treatment and subsequent surgical resection for local control. Many trial have
      now shown the feasibility of neoadjuvant therapy and suggest that overall
      survival is approximately double that seen after surgical resection or radiation
      alone. Future clinical trials will define whether surgical resection after
      induction therapy provides better local and control and survival than
      chemotherapy and high-dose radiation alone.

PMID- 8553673
TI  - Treatment of unresectable lung cancer with brachytherapy.
AB  - Endobronchial brachytherapy is an evolving treatment modality. Although standard
      clinical indications and dosage schedules have not yet been established, the wide
      range of individual experience overwhelmingly demonstrates its efficacy in
      palliating lung cancer patients who generally have limited treatment options.
      Although the exact complication rate is not known, it appears to be low and the
      potential benefits far outweigh the risks. The role of endobronchial
      brachytherapy for cure is less clear. For most instances "prolonged palliation"
      would be a more suitable term than "cure." Further data is needed to clarify the
      proper place of endobronchial brachytherapy as a boost to external beam radiation
      therapy. The dose, fractionation scheme, and timing relative to external beam
      radiation therapy are based on institutional preference at this time. The
      historical evolution, treatment technique, results, and complications of
      endobronchial brachytherapy are reviewed here.

PMID- 8553676
TI  - Multidisciplinary approach to the treatment of unresectable breast cancer.
AB  - Between January 1960 and December 1990, 163 patients with locally advanced breast
      cancer (LABC) were treated by multidisciplinary treatment regimens. Forty-six
      cases received preoperative intraarterial perfusion of cytotoxic drugs. Fifty
      four cases received preoperative systemic chemotherapy. Forty-one cases received
      preoperative radiotherapy, and twenty-two cases received both radiotherapy and
      chemotherapy. Preoperative systemic chemotherapy gives the best results.
      Postoperative chemotherapy and radiotherapy did not improve the survival rate as
      compared to the control group. The authors suggest that preoperative induction
      chemotherapy be used for LABC patients.

PMID- 8553675
TI  - Angiotensin II (AII) induced hypertension chemotherapy (IHC) for unresectable
      gastric cancer: with reference to resection after down staging.
AB  - Angiotensin II induced hypertension chemotherapy (IHC) is a drug delivery system
      for augmentation of anti-cancer effects on the experimental basis of the
      functional difference of microcirculation between tumor and normal tissue. Blood
      flow in tumor tissue increased selectively when the blood pressure was elevated
      by the infusion of angiotensin II. Two randomized controlled trials (RCT) for
      advanced gastric cancer using AFM regimen; a combination of adriamycin (ADM), 5
      fluorouracil (5-FU), and mitomycin (MMC), showed increased response rate by IHC
      (response rate: IHC/non-IHC; 42.9% vs 10.5% in RCT-1, and 31.3% vs 6.7% in RCT-2,
      respectively). Toxicities were not different statistically between groups. In
      phase II for stage IVB gastric cancer patients (the criteria according to the
      General Rules of the Gastric Cancer Study of Japanese Research Society for
      Gastric Cancer), 5 complete response (CR) and 10 partial response (PR) (58%) were
      observed out of 26 unresectable cases without prior chemotherapy. Moreover, 5 of
      15 responders could received curative gastrectomy and obtained conclusive down
      staging (19%). Here we discuss the role of enhancement of drug delivery for
      cancer chemotherapy on the basis of a series of clinical and experimental
      evidences.

PMID- 8553674
TI  - Comparison of different treatments for unresectable esophageal cancer.
AB  - Many patient with esophageal cancer have advanced disease that in not amenable to
      curative treatment. For these individuals the relief of dysphagia is of utmost
      importance to the quality of their remaining survival time. This article reviews
      and compares the methods of palliation with focus on indications and
      contraindications, advantages as well as disadvantages of each technique, success
      rates, and complications. Tumor characteristics, the physician's experience, the
      institution's capabilities, cost, and patient preference will influence choice of
      palliation. Methods are often complementary rather than competitive.

PMID- 8553677
TI  - Enhancement of biliary carcinogenesis in hamsters by cholecystokinin.
AB  - We recently developed a new model for rapid and reproducible induction of biliary
      carcinoma in hamsters. In the present study, we evaluated the effects of
      cholecystokinin (CCK), which has a trophic action on the gastrointestinal tract
      and on the pancreaticobiliary system, on biliary carcinogenesis in this hamster
      model. Hamsters treated with N-nitrosobis (2-oxopropyl) amine (BOP) were divided
      into four groups: In Group I, hydrolyzed gelatin, a solvent of CCK, was injected
      subcutaneously. In Groups II and III, CCK 2.5 and 25 microgram/kg were
      administered, respectively. In Group IV loxiglumide, a CCK receptor antagonist,
      was administered. CCK significantly promoted the carcinogenetic effect of BOP in
      the intra- and extrahepatic bile ducts but not in the gallbladder or pancreas.
      Loxiglumide exerted an inhibitory effect on carcinogenesis in the intrahepatic
      bile duct.

PMID- 8553678
TI  - Selection criteria for endoscopic retrograde cholangiopancreaticography (ERCP) in
      patients with gallstone disease.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) has been used in patients
      referred to cholecystectomy when clinical information, biochemical values, or
      ultrasonography (clinical characterization) have indicated possible presence of
      common bile duct stones. A retrospective study of 599 patients treated for
      gallstone disease was used to develop a characterization procedure for predicting
      common bile duct stones by a discriminant analysis procedure. The variables
      selected by the analysis as the best combination for CBDS prediction were age
      (years), the values of bilirubin (micromol/l), ALAT (U/l) and gamma GT (U/l). The
      characterization was false positive in 22 cases (3.7%) and false negative in 11
      cases (1.8%), compared to 198 false positive cases (33.1%) and three false
      negative cases (0.5%) by the clinical characterization. A leaving-one-out
      correction did not change the results. In a test set of 157 cholecystectomy
      patients, clinical characterization was false positive in 44.6% of the patients,
      compared to 4.5% false positive results when using the discriminant analysis
      procedure. The discriminant analysis procedure would have missed one patient with
      common bile duct stones. Selection by the discriminant analysis characterization
      procedure seems to reduce the frequency of preoperative ERCP significantly
      without an increase in undetected common bile duct stones.

PMID- 8553679
TI  - Laparoscopic cholecystectomy--can conversion be predicted?
AB  - The possibility of conversion to open cholecystectomy (OC) always exists while
      performing a laparoscopic cholecystectomy (LC). This study has been performed
      with the aim of identifying factors predicting conversion to OC. From October
      1992-April 1994, LC was attempted in 150 patients and conversion to OC was
      required in 29 (19%) patients. Ten preoperative factors were analyzed
      retrospectively to identify parameters significantly correlating with conversion
      to OC. Preoperative factors analyzed were age, sex, duration of symptoms, BMI
      (Body Mass Index), past history of jaundice, previous abdominal surgery,
      associated medical risk factors, palpable lump on clinical examination, USG, and
      OCG findings. Univariate and multiple stepwise regression analysis identified
      male sex, USG finding of contracted/thick-walled gall bladder, and a palpable
      gall bladder lump on examination as significant preoperative factors predicting
      conversion to OC.

PMID- 8553680
TI  - Leukocyte activation by isolated hyperthermic liver and limb perfusion due to
      malignancy.
AB  - Fourteen patients with liver tumor malignancy and sixteen patients with malignant
      melanoma localized to one limb were studied regarding leukocyte activation with
      the release of polymorphonuclear neutrophilic (PMN) elastase and of neopterin and
      formation of cytokines (TNF-alpha and IL-6) during the surgical treatment.
      Patients undergoing liver resection (n = 10), abdominal hysterectomy (n = 10), or
      hip replacement surgery (n = 10) served as control groups. Isolated hyperthermic
      liver perfusion was performed with cytostatic-containing perfusate (melphalan and
      cisplatinum). Patients with recurrent malignant melanoma confined to one limb
      underwent isolated hyperthermic limb perfusion with cytostatic-containing
      perfusate (melphalan). Blood samples for determination of PMN elastase,
      neopterin, TNF-alpha, and IL-6 were drawn from the patients preoperatively, 1
      minute before the start of the perfusion, 60 and 120 minutes after the start of
      the perfusion, and 24 hours postoperatively. Samples from the perfusate were
      drawn 60 minutes after the start of the perfusion. High concentration of plasma
      PMN elastase were found in both patients undergoing liver and limb perfusion and
      in patients undergoing liver resection surgery. Elevated concentrations of IL-6
      were found in the patients undergoing liver perfusion and in patients undergoing
      liver resection. In none of the patients were there increased concentrations of
      neopterin or TNF-alpha. The perfusate contained high concentrations of PMN
      elastase, neopterin, and IL-6. This study also demonstrated that major surgery
      leads to elevated concentrations of PMN elastase and IL-6. An increase of PMN
      elastase and IL-6 was seen in response to perfusion and to surgical trauma.

PMID- 8553682
TI  - Protective effects of Osbeckia octandra against paracetamol-induced liver injury.
AB  - 1. Osbeckia octandra is a plant used in traditional medicine to treat jaundice
      and other liver disorders. In this study, the effects of Osbeckia leaf extract on
      paracetamol-induced liver injury were investigated both in vivo in mice and in
      rat hepatocytes in vitro. 2. Oral administration of Osbeckia extract (330 mg/kg)
      at the same time as paracetamol (450 mg/kg) to mice, resulted in a significant
      protection (p < 0.05) against liver damage, as assessed by improvements in the
      blood Normotest (39.1 +/- 1.9 versus 46.3 +/- 2.0 s), total liver glutathione
      (730 +/- 39 versus 574 +/- 27 micrograms/250 mg liver), plasma aspartate
      aminotransferase level (916 +/- 225 versus 1965 +/- 291 iu/l), and liver
      histopathology at 24 h after paracetamol administration. 3. In experiments to
      assess the direct effects of Osbeckia extract, significant protection was also
      found in freshly isolated rat hepatocytes against damage induced by 185 microM
      2,6-dimethyl N-acetyl p-quinoneimine (2,6-diMeNAPQI, an analogue of NAPQI, the
      toxic metabolite of paracetamol) in vitro. When Osbeckia extract (500
      micrograms/ml) was added to the incubation medium at the same time as 2,6
      diMeNAPQI significant changes in cell viability (78.4 +/- 3.3 versus 47.2 +/-
      5.8% of control, p < 0.001), cell reduced glutathione (GSH) level (35.0 +/- 3.1
      versus 23.8 +/- 1.5%, p = 0.009), and reduced release of lactate dehydrogenase
      (129.9 +/- 6.6 versus 224.6 +/- 12.1%, p < 0.001) were demonstrated after 1 h
      incubation as compared with 2,6-diMeNAPQI alone. 4. Significant protection was
      still obtained against 2,6-diMeNAPQI in vitro when addition of Osbeckia extract
      was delayed by 20 min. These results indicate that Osbeckia extract can protect
      against paracetamol-induced liver injury.

PMID- 8553681
TI  - Long-term changes in bone mass after partial gastrectomy in a well-defined
      population and its relation to tobacco and alcohol consumption.
AB  - We studied the long-term effect of partial gastrectomy on bone metabolism in a
      well defined population of gastrectomized patients compared to an age- and sex
      matched group with unoperated peptic ulcers (controls). We selected 61
      individuals between 61 and 70 years old at the time of investigation who had been
      operated on at the same surgical department an average of 20 years earlier.
      Compared to unoperated ulcer patients, we found reduced bone mass of the distal
      forearm in the operated groups. The serum level of calcidiol was significantly
      reduced in Billroth I (BI) operated women and insignificantly lower in the other
      operated groups. In men, ionized and total calcium was reduced, and 24-hour
      excretion of hydroxyproline in the urine as increased (p < 0.05). Biochemical
      signs of osteomalacia were found in one gastrectomized patient only. There were
      no significant differences between operated and unoperated patients in serum
      levels of alkaline phosphatases, iPTH, calcitriol, or the 24-hour urine
      calcium/creatinine excretion, even though there was a trend toward lower 24-hour
      urine calcium/creatinine ratio and increased levels in iPTH in the operated
      groups. There was no correlation between the daily alcohol consumption or
      cumulative tobacco consumption and bone mineral content in each group.
      Gastrectomized women smoked much more than control women, and smoking may be a
      determinant factor for the bone loss, as it is in healthy persons. Operated
      patients had a lower intake of milk products. All patients were exposed to
      sunlight for more than 3 hours/week. It is suggested that osteopenia after
      gastrectomy might be caused by calcium depletion rather than lack of vitamin D.
      The consumption of tobacco but not of alcohol was connected to bone loss.

PMID- 8553683
TI  - Metabolism of methoxyphenamine and 2-methoxyamphetamine in P4502D6-transfected
      cells and cell preparations.
AB  - 1. Control and P4502D6-transfected human B-lymphoblastoid cell lines (cHol and
      h2D6v2 respectively) were used to study 2D6-mediated metabolism of
      methoxyphenamine (MPA) and 2-methoxyamphetamine (2MA). The main metabolites were
      products of O-dealkylation and aromatic hydroxylation at the 5-position. In
      addition, N-desmethyl-methoxyphenamine (NDMP) was also identified as a minor
      metabolite of MPA in extracts of these cells, confirming previous reports of 2D6
      mediated N-demethylation of MPA. 2. An additional ring-hydroxylated metabolite of
      MPA and 2MA has been tentatively identified as the corresponding 3-hydroxy-2
      methoxy derivative. 3. MPA metabolism in whole cells was time dependent, with
      approximately 30% of the MPA metabolized after 72 h. A 35% conversion of MPA was
      achieved on average with cell lysates. Only 18% 2MA was metabolized. By contrast,
      control cells (cHol) showed no evidence of any MPA or 2MA metabolites even after
      96-h incubation. 4. Continuous presence of haemin/dimethylsulphoxide (DMSO)
      throughout the 4-day incubation with MPA resulted in a shift in the metabolite
      profile towards the production of NDMP at the expense of the other products. 5.
      In summary, h2D6v2 cells, lysates and microsomes can form all metabolites of MPA
      and can be used in drug interaction studies.

PMID- 8553684
TI  - Kinetics of diazepam metabolism in rat hepatic microsomes and hepatocytes and
      their use in predicting in vivo hepatic clearance.
AB  - 1. The rates of diazepam (DZ) metabolism to the primary metabolites 3
      hydroxydiazepam, 4'-hydroxydiazepam and nordiazepam were studied in vitro using
      rat hepatic microsomes and hepatocytes. 4'-hydroxydiazepam had the largest
      intrinsic clearance (Vmax/Km ratio, CL(int)) in both microsomes and hepatocytes
      representing 49 and 70% of total metabolism respectively. Whereas the
      contribution of 3-hydroxydiazepam was similar in both systems (21-24%), the N
      demethylation pathway was greater in microsomes (27%) than hepatocytes (9%). 2.
      The pharmacokinetics of DZ were determined in vivo using the intraportal route to
      avoid blood flow limitations due to the high clearance of DZ. No dose dependency
      was observed in either clearance or steady state volume of distribution, which
      were estimated to be 38 ml/min/SRW (where SRW is a standard rat weight of 250 g)
      and 1.3 L/SRW respectively. Blood binding of DZ was concentration independent,
      the unbound fraction being 0.22. 3. Scaling factors were used to relate the in
      vitro CL(int) to the in vivo unbound clearance. Hepatocytes (123 ml/min/SRW)
      produced a more realistic prediction for the in vivo value (174 ml/min/SRW) than
      microsomes (41 ml/min/SRW). This situation is believed to arise from the
      quantitative differences in the three metabolic pathways in the two in vitro
      systems. It is speculated that end product inhibition is responsible for reduced
      total metabolism in microsomes whereas hepatocytes operate kinetically in a
      manner close to in vivo.

PMID- 8553685
TI  - Determination of P4501A2 activity in human liver microsomes using [3-14C
      methyl]caffeine.
AB  - 1. Caffeine N3-demethylation, the major pathway of caffeine metabolism in man, is
      mediated by P4501A2. The carbon of the methyl group lost during N3-demethylation
      is eliminated as carbon dioxide in vivo, or as formaldehyde and formic acid in
      vitro. 2. A simple and sensitive assay was developed to quantify the
      [14C]formaldehyde/[14C]formic acid produced following incubation of human
      microsomes with [3-14C-methyl]caffeine. This assay, using solid-phase extraction,
      enables quantitation of [14C]formaldehyde/[14C]formic acid with acceptable
      precision (within 5%) and accuracy (within 10%). 3. Typical Km and Vmax for the
      N3-demethylation of caffeine were determined by this assay to be 500 (range 220
      1200) microM, and 250 (range 115-450) pmol.mg protein-1.min-1 respectively. 4.
      The N3-demethylation activity determined in microsomes from a range of human
      livers correlated significantly with other P4501A2 activities (p < 0.001) and was
      inhibited (> 95%) by furafylline. In addition, caffeine N3-demethylation was
      catalysed by microsomes from cell lines transfected with human P4501A2 cDNA. 5.
      This assay, for quantitation of [14C]formaldehyde/[14C]formic acid in human liver
      microsomes, is suitable for use in in vitro drug interaction studies as a probe
      for P4501A2 activity.

PMID- 8553686
TI  - A cytochrome P4502B form is the major bioactivation enzyme for the pyrrolizidine
      alkaloid senecionine in guinea pig.
AB  - 1. We have purified three P450s from the liver of the phenobarbital (PB)-treated
      guinea pig in order to evaluate the role of these enzymes in pyrrolizidine
      alkaloid (PA) metabolism. 2. PB treatment of guinea pig increased the hepatic
      microsomal conversion of the PA senecionine (SN) to the pyrrolic metabolite (+/
      )6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP), an activation
      product, and SN N-oxide, a detoxification product by 224 and 70% respectively. 3.
      Reconstitution of a PB-inducible guinea pig P4502B isoform (M(r) = 57,512 by
      MALDI-TOF mass spectrometry) in a reconstituted system metabolized SN to DHP and
      SN N-oxide at rates of 1.98 and 1.45 min-1 respectively. A second purified guinea
      pig P450, a 2C-type isoform (M(r) = 56,496 by MALDI-TOF mass spectrometry),
      produced SN N-oxide from SN at the rate of 13.3 min-1 but catalyzed little DHP
      formation. The third guinea pig P450, an apparent 3A type (M(r) = 54-56,000 by
      SDS-PAGE), lost its catalytic activity towards SN during the final purification
      process. 4. Immunoinhibition of microsomal SN metabolism by rabbit antibodies
      raised against the guinea pig P4502B, 2C and 3A isoforms indicated that the 2B
      played the most important role (> 70% of the total metabolism) in bioactivation
      of SN in both the untreated or PB-treated guinea pig, whereas 2C and 3A seemed to
      exhibit little (around 13%) PA metabolism. P4502B, along with flavin-containing
      monooxygenase, also contributed to the detoxification of SN in both the untreated
      (34%) and PB-treated (40%) guinea pig. 5. This study suggests that the putative
      P4502B form plays the most important role in SN bioactivation in guinea pig.

PMID- 8553687
TI  - Extrahepatic expression of P450 proteins in insulin-dependent diabetes mellitus.
AB  - 1. Male Wistar rats were rendered diabetic by the administration of a single
      intraperitoneal dose of streptozotocin; the levels of the xenobiotic-inducible
      P450 proteins were determined in the lung and kidney using diagnostic substrates
      and immunoblotting employing polyclonal antibodies. The glutathione conjugation
      system in the cytosol of these tissues was also investigated. 2. The onset of
      insulin-dependent diabetes did not influence the O-dealkylations of
      methoxyresorufin, ethoxyresorufin and pentoxyresorufin in either kidney or lung.
      3. Lauric acid hydroxylase activity, however, was induced in the kidney but no
      activity was detectable in the lung. Immunoblot analysis of kidney microsomes
      using antibodies to P4504A1 revealed the presence of two bands, both of which
      were clearly inducible in diabetes. In pulmonary microsomes a single faint band
      was detected which also appeared to be higher in the diabetic rats. 4. Aniline p
      hydroxylase activity was not detectable in the kidney, but activity was
      measurable in the lung and was suppressed in diabetes. Immunoblot analysis of
      pulmonary microsomes using antibodies to P4502E1 immunodetected a single band
      which was suppressed in diabetes. In the kidney microsomes a single band was also
      detected which was, however, markedly elevated in diabetes. 5. Glutathione S
      transferase activity was modestly higher in the kidney, but not lung, of the
      diabetic animals. Glutathione reductase and total glutathione levels were not
      influenced by the presence of diabetes. 6. It is concluded that streptozotocin
      induced insulin-dependent diabetes modulates extrahepatic P450 proteins, the
      effect being both tissue- and isoform-specific.

PMID- 8553688
TI  - Metabolic pathways of 4-[(3-methoxyphenyl)methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza
      2,6- disilacyclohexane (MPSC) hydrochloride, a silicon-containing xenobiotic, in
      rat, dog, and man.
AB  - 1. The metabolic pathways of Sandoz compound 58-112, 4-[(3-methyoxyphenyl)
      methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza-2,6- disilacyclohexane (MPSC)
      hydrochloride were evaluated in rat, dog, and man after a single oral dose. 2. In
      rat, dog and man the major route of elimination was renal. In the dog, renal
      excretion of unchanged MPSC represented a substantial portion of the dose whereas
      in rat and man MPSC was completely metabolized prior to excretion. 3. In rat and
      man, the major end-product metabolite was 3'-[((hydroxydimethylsilyl)
      methylamino)methyl]-phenol glucuronide; 4-[(3-hydroxyphenyl)-methyl]-2,2,6,6
      tetramethyl-1-oxa-4-aza-2,6- disilacyclohexane and 4-[(4-hydroxy-3-methoxyphenyl)
      methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza-2 ,6- disilacyclohexane and their
      conjugates were also present. In dog, the major end-product metabolites were the
      hippurate of 3-methoxybenzoic acid and 3-hydroxybenzoic acid.

PMID- 8553689
TI  - Metabolites of 2-chlorosyringaldehyde in fish bile: indicator of exposure to
      bleached hardwood effluent.
AB  - 1. 2-Chlorosyringaldehyde (2-CSA) is the major chlorinated phenol produced by the
      100% chlorine dioxide bleaching of eucalypt pulp and is found in other bleached
      hardwood effluents. Almost nothing is known of the environmental or metabolic
      fates of this chemical. 2. Sand flathead (Platycephalus bassensis) was given 2
      CSA by intraperitoneal injection at 0.15, 1.5, 15 and 75 mg/kg doses and, 4 days
      later, bile was collected and solvent extracted before and after enzymatic
      cleavage of conjugates. The acetate derivatives of bile extracts were analysed by
      gas chromatography/mass spectrometry. 3. The major metabolite 4 days after
      administration was the glucuronide or sulphate conjugate of 2-chloro-4-hydroxy
      3,5-dimethoxy-benzylalcohol (2-CB-alcohol). The identity of 2-CB-alcohol was
      confirmed by chemical synthesis. 4. The quantity of 2-CB-alcohol in the bile was
      linearly related to dose of 2-CSA and was detected at all dose levels. Minor
      metabolites identified were conjugated 2-CSA, unchanged 2-CSA and 2-chloro-4
      hydroxy-3,5-dimethoxy-benzoic acid. 5. The amount of 2-CB-alcohol in bile has the
      potential to be a sensitive and specific indicator of fish exposure or bleached
      hardwood effluent.

PMID- 8553690
TI  - Aminopyrine infusion breath test for the determination of changes in P450
      metabolism in vivo.
AB  - 1. An osmotic mini-pump was used to maintain a constant infusion of radiolabelled
      [N-dimethyl-14C] aminopyrine into a rat. After implanting the mini-pump, 14CO2
      expiration rate was constant within 12 h, and this rate was maintained for 192 h.
      2. Treatment with 2-diethylaminoethyl-2,2-diphenylvalerate HCl (SKF 525-A) or
      cimetidine, inhibitors of P450-dependent metabolism, resulted in both dose- and
      time-dependent inhibition of the expiration of 14CO2.

PMID- 8553691
TI  - Metabolism of a novel antiarrhythmic agent, bidisomide, in man: use of high
      resolution mass spectrometry to distinguish desisopropyl bidisomide from
      desacetyl bidisomide.
AB  - 1. Metabolism of bidisomide, a novel antiarrhythmic agent, was studied in man,
      and was not extensive as evidenced by the fact that approximately 60 and 70% of
      the radioactive doses were recovered as the parent drug after i.v. and oral
      administration respectively. 2. The mass spectra of bidisomide metabolites
      indicate that the two major metabolic pathways of bidisomide were hydroxylation
      of the piperidine ring and N-dealkylation. The latter occurred on the side chain
      containing the piperidine ring or the isopropyl group. The N-dealkylated
      metabolite on the side chain containing the piperidine ring was cyclized to
      result in a pyrrolidone metabolite. 3. The N-dealkylated metabolite, desisopropyl
      bidisomide, was identified by comparing its high resolution mass spectrum to that
      of authentic desacetyl bidisomide. 4. In the hydroxylation pathway, both mono-
      and dihydroxylated metabolites of the piperidine ring were observed. The exact
      location of the hydroxyl groups on the piperidine ring was not determined.

PMID- 8553692
TI  - Kinetics and disposition of picumeterol in animals.
AB  - 1. The pharmacokinetics and disposition of picumeterol, a novel beta 2 receptor
      agonist agent, have been studied in the rat and dog following administration by
      inhalation, intravenous and oral routes at various dose levels. 2. Picumeterol
      was found to be transferred across the lung of the rat and dog following
      inhalation dosage. After i.v. dosage picumeterol was eliminated from plasma with
      a half-life of about 1 h in the rat and about 2 h in the dog. Plasma clearance in
      the rat was about twice liver blood flow and the plasma levels of picumeterol
      were low after oral administration. 3. Following instillation of 14C-picumeterol
      to the trachea of isolated respiring rat lung preparations radioactivity was
      transferred from the airways to perfusion media as unchanged drug within 2 min.
      After 2 h perfusion, no metabolites were detected in the recirculation perfusate
      or lung. 4. Picumeterol was extensively metabolized in vivo in the rat (about
      95%) and dog (about 90%) and in vitro in microsomal preparations of rat, dog and
      human liver. O-dealkylation and beta-oxidation are important as routes of
      metabolism. 5. Radioactivity was largely excreted in the urine of the rat and dog
      (> 50% of dose), as metabolites, following i.v. administration. There was some
      excretion of radioactivity in dog bile. Extensive first-pass metabolism was found
      after oral administration in the rat.

PMID- 8553693
TI  - Molecular characterization of the PEL1 gene encoding a putative
      phosphatidylserine synthase.
AB  - In the yeast Saccharomyces cerevisiae the PEL1 gene is essential for the
      viability of rho-/rhoo petite mutants, and its mutation in respiring cells
      results in a pleiotropic phenotype. Results of complementation analysis with
      different subclones of chromosomal DNA and re-sequencing of the YCL4w-YCL3w
      segment of chromsome III demonstrate that the coding region of the PEL1 gene
      corresponds to 1467 bp. The size of the PEL1 transcript in Northern blot analysis
      was estimated to be approximately 1.5 kb. Transcription initiation in wild-type
      cells was found to occur at the position -9 relative to the ATG. The PEL1 gene
      was moderately expressed irrespective of the state of the mitochondrial genome
      and the nature of the carbon sources. Disruption of the PEL1 gene was not lethal
      and resulted in the same phenotype as observed with the pel1 mutant, i.e. the
      cells were not able to survive ethidium bromide mutagenesis, were thermosensitive
      for growth on glucose at 37 degrees C and failed to grow on minimal glycerol
      medium. Although the Pel1 protein exhibits significant similarity to a family of
      phosphatidylserine synthases, the disrupted PEL1 gene was not complemented by the
      multicopy plasmid-borne CHO1 gene encoding an essential yeast phosphatidylserine
      synthase.

PMID- 8553694
TI  - DOGR1 and DOGR2: two genes from Saccharomyces cerevisiae that confer 2
      deoxyglucose resistance when overexpressed.
AB  - Saccharomyces cerevisiae contains two genes (DOGR1 and DOGR2) that are able to
      confer 2-deoxyglucose resistance when they are overexpressed. These genes are
      very similar, sharing 92% identity at the protein level. They code for two
      isoenzymes with 2-deoxyglucose-6 phosphate (2-DOG-6P) phosphatase activity. These
      enzymes have been purified and characterized. DogR1p shows an optimum pH of 6, an
      optimum temperature of 30 degrees C and a KM on 2-DOG-6P of 17 mM. DogR2p shows a
      similar optimum pH, but the optimum temperature is 40 degrees C and it exhibits a
      KM on 2-DOG-6P of 41 mM. Both enzymes require 10 mM-MgCl2 for maximal activity
      and they are inhibited by inorganic phosphate.

PMID- 8553695
TI  - A disruption-replacement approach for the targeted integration of foreign genes
      in Hansenula polymorpha.
AB  - A system has been developed which allows the selection of integrative
      transformants with replacement of the Hansenula polymorpha methanol oxidase gene
      (MOX) with expression cassettes carrying heterologous gene under the control of
      the MOX promoter. The system is convenient for comparison of the expression
      levels of different constructs integrated into the same locus of the H.
      polymorpha genome. This system was used to compare the secretion levels of human
      urinary plasminogen activator, the secretion of which was directed by different
      signal sequences.

PMID- 8553696
TI  - Schizosaccharomyces pombe RNase MRP RNA is homologous to metazoan RNase MRP RNAs
      and may provide clues to interrelationships between RNase MRP and RNase P.
AB  - RNase MRP and RNase P ribonucleoproteins are structurally and functionally
      similar across a large evolutionary distance. To better characterize possible
      complex interrelationships between these two enzymes, we have employed the
      fission yeast Schizosaccharomyces pombe. Unlike Saccharomyces cerevisiae, S.
      pombe is believed to harbour only one genetic locus for the RNA component of
      RNase P and does not contain a known mitochondrially encoded RNase P RNA. We have
      identified the single nuclear gene for the RNA component of RNase MRP in S.
      pombe, mrp-1, by homology to vertebrate RNase MRP RNAs. The mrp-1 gene encodes an
      RNA of maximum mature length 400 nucleotides that shares a high degree of
      identity, in evolutionarily conserved regions, to both vertebrate RNase MRP RNAs
      and S. pombe RNase P RNA. Disruption of mrp-1 in the diploid strain SP826 and
      sporulation of tetrads resulted in a 2 dead:2 viable segregation, consistent with
      the gene being essential. Lethality is rescued by a plasmid-borne copy of mrp-1.
      Partially purified ribonucleoprotein RNase MRP activity correctly and efficiently
      processed all previously characterized heterologous mitochondrial RNA substrates.
      The compact mitochondrial genome of S. pombe contains sequence elements with >
      50% identity to mammalian D-loop CSBI and CSBII elements. The identification of
      mrp-1 in S. pombe should facilitate not only comparisons between the related
      ribonucleoproteins RNase MRP and RNase P, but should also provide an opportunity
      for genetic elucidation of RNase MRP function in a situation reflective of the
      animal kingdom.

PMID- 8553697
TI  - Use of polymerase chain reaction epitope tagging for protein tagging in
      Saccharomyces cerevisiae.
AB  - Epitope tagging is the insertion of a short stretch of amino acids constituting
      an epitope into another protein. Tagged proteins can be identified by Western,
      immunoprecipitation and immunofluorescence assays using pre-existing antibodies.
      We have designed vectors containing the URA3 gene flanked by direct repeats of
      epitope tags. We use the polymerase chain reaction (PCR) to amplify the tag-URA3
      tag cassette such that the ends of the PCR fragments possess homology to the gene
      of interest. In vivo recombination is then used to direct integration of the
      fragment to the location of interest, and transformants are selected by their
      Ura+ phenotype. Finally, selection for Ura- cells on 5-fluoro-orotic acid plates
      yields cells where recombination between the repeated epitopes has 'popped out'
      the URA3 gene, leaving a single copy of the epitope at the desired location. PCR
      epitope tagging (PET) provides a rapid and direct technique for tagging that does
      not require any cloning steps. We have used PET to tag three Saccharomyces
      cerevisiae proteins, Cln1, Sic1 and Est1.

PMID- 8553698
TI  - Precise gene disruption in Saccharomyces cerevisiae by double fusion polymerase
      chain reaction.
AB  - We adapted a fusion polymerase chain reaction (PCR) strategy to synthesize gene
      disruption alleles of any sequenced yeast gene of interest. The first step of the
      construction is to amplify sequences flanking the reading frame we want to
      disrupt and to amplify the selectable marker sequence. Then we fuse the upstream
      fragment to the marker sequence by fusion PCR, isolate this product and fuse it
      to the downstream sequence in a second fusion PCR reaction. The final PCR product
      can then be transformed directly into yeast. This method is rapid, relatively
      inexpensive, offers the freedom to choose from among a variety of selectable
      markers and allows one to construct precise disruptions of any sequenced open
      reading frame in Saccharomyces cerevisiae.

PMID- 8553699
TI  - DNA sequence analysis of a 13 kbp fragment of the left arm of yeast chromosome XV
      containing seven new open reading frames.
AB  - The sequence of a 13 kbp fragment located in the vicinity of the left telomere of
      chromosome XV (cosmid pEOA179) has been determined. Seven new open reading frames
      (ORFs) encoding polypeptides longer than 100 residues have been found (AOB629,
      AOA342, AOC231, AOE555, AOE236, AOA236 and AOE1045). Three of them show no
      identity with proteins deposited in the data banks. ORF AOB629 (629 amino acids)
      has some similarity with previously described ferric reductases from
      Saccharomyces cerevisiae and Schizosaccharomyces pombe. ORF AOA342 encodes a
      polypeptide reminiscent of dihydroflavonol-4-reductases from a number of plant
      species. AOE236 displays a high level of identity when compared with peroxisomal
      membrane proteins previously cloned from the methylotrophic yeast Candida
      boidinii. Finally, AOE1045 encodes a large protein (1045 residues) with some
      identity with a hypothetical 147 kDa protein identified during the sequencing of
      Caenorhabditis elegans chromosome 3.

PMID- 8553700
TI  - Sequence analysis of the ADE2 gene coding for phosphoribosylaminoimidazole
      carboxylase in Schwanniomyces occidentalis.
AB  - We have determined the nucleotide sequence of a 3.3 kb fragment containing the
      gene (ADE2) encoding phosphoribosylaminoimidazole carboxylase (AIRC) from the
      yeast Schwanniomyces occidentalis. Translation of a 1671 bp open reading frame
      predicts a protein of 557 amino acids which has significant homology to AIRC from
      Saccharomyces cerevisiae and Schizosaccharomyces pombe. The 5' untranslated
      region of the S. occidentalis gene contains a sequence corresponding to the
      consensus binding site of the S. cerevisiae transcription regulatory proteins
      GCN4, BAS1 and BAS2.

PMID- 8553701
TI  - Isolation of phosphoribosylpyrophosphate synthetase (PRS1) gene from Candida
      albicans.
AB  - We have isolated a 3.7 kb EcoR1 fragment from a genomic library of Candida
      albicans which displayed a 65% level of identity with the PRS gene family (PRS)
      of Saccharomyces cerevisiae. The PRS gene encodes a phosphoribosylpyrophosphate
      (PRPP) synthetase of S. cerevisiae, which catalyses the synthesis of purines,
      pyrimidines, and amino acids such as histidine and tryptophan. By Northern
      analyses, we observed that the entire 3.7 kb EcoR1 fragment as well as 1.1 kb
      KpnI-SacI internal fragment of the 3.7 kb EcoR1 fragment hybridized to the same
      1.4 kb transcript. An internal 2.6 kb KpnI fragment was subcloned and sequenced.
      A deduced sequence of 321 amino acids representing a polypeptide of 35.2 kDa was
      determined. A FASTA search indicated that the C. albicans PRS (Ca PRS1) had an
      overall homology at the amino acid level of 91% with the S. cerevisiae PRS3.
      Putative transcriptional start and termination sequences as well as a cation
      binding, PRPP synthetase signature sequence were identified. Ca PRS1 was
      localized to chromosome 2 of the C. albicans genome. Low stringency
      hybridizations indicates that the organism may possess multiple PRS genes. The
      function of these genes in nitrogen signaling is discussed.

PMID- 8553702
TI  - Sequence analysis of a 30 kb DNA segment from yeast chromosome XIV carrying a
      ribosomal protein gene cluster, the genes encoding a plasma membrane protein and
      a subunit of replication factor C, and a novel putative serine/threonine protein
      kinase gene.
AB  - We have determined the nucleotide sequence of a 30 kb fragment of chromosome XIV
      of Saccharomyces cerevisiae. The sequence revealed the presence of 19 open
      reading frames (ORFs) longer than 300 bp. NO422 and NO425 correspond to the split
      ribosomal protein genes encoding S16A and rp28, respectively, NO450 displays a
      striking similarity with serine/threonine protein kinase genes, in particular
      with STE20, and therefore may encode a novel member of this protein family. NO453
      is the longest ORF in this DNA segment, having a size of 4908 bp, but its
      function is not yet known. NO530 encodes the plasma membrane protein Mid1p and
      NO533 corresponds to the gene coding for a 40 kDa subunit of replication factor
      C. The remaining ORFs show weak or no homology with proteins in the data bases.

PMID- 8553703
TI  - GUF1, a gene encoding a novel evolutionarily conserved GTPase in budding yeast.
AB  - While sequencing a region of chromosome IV adjacent to the checkpoint gene MEC3,
      we identified a gene we call GUF1 (GTPase of Unknown Function), which predicts a
      586 amino acid GTPase of the elongation factor-type class. The predicted Guf1p
      protein bears striking sequence similarity to both LepA from Escherichia coli
      (43% identical) and LK1236.1 from Caenorhabditis elegans (42% identical).
      Analysis of both a guf1 delta deletion and a putative constitutive-activating
      mutant (GUF1HG) revealed that GUF1 is not essential nor did mutant cells reveal
      any marked phenotype.

PMID- 8553704
TI  - Clone bank of the mitochondrial genome of yeast Hansenula wingei.
AB  - For sequencing, mitochondrial DNA from Hansenula wingei yeast was digested with
      various restriction enzymes and the resultant DNA fragments were cloned into a
      pEMBL phasmid vector. Our clone bank consists of 39 overlapping clones which
      cover the entire 27,694 bp region of the H. wingei mitochondrial genome.

PMID- 8553705
TI  - Current awareness on yeast.

PMID- 8553706
TI  - Characteristics of Staphylococcus aureus strains isolated from bovine mastitic
      milk: bacteriophage and antimicrobial agent susceptibility, and
      enterotoxigenicity.
AB  - Staphylococcus aureus strains isolated from bovine mastitic milk in Trinidad were
      examined for their susceptibility to bacteriophages and antimicrobial agents and
      their ability to produce enterotoxins. Phage 42D was used to screen for bovine
      strains of S. aureus in milk. Of 250 strains tested, 224 (89.6%) were sensitive
      to phages in the international phage set (IPS), 85 (34.0%) were resistant to
      antimicrobial agents and 134 (53.6%) were enterotoxigenic. Strains lysed by
      phages in various groups (mixed) were prevalent, 145 (58.0%), followed by strains
      sensitive to groups III (17.0%) and I (8.8%) phages. A total of 72 (28.8%)
      strains were lysed by phage 42D either alone or with others. Resistance to
      penicillin was most common with 59 (23.6%) strains while 44 (17.6%) and 43
      (17.2%) strains were resistant to ampicillin and triple sulphur respectively.
      Only 3 (1.2%) strains were resistant to methicillin. Prevalence of resistance to
      penicillin (12.5%) amongst phage 42D-sensitive strains was significantly (P < or
      = 0.01; X2) lower than for strains not lysed by phage 42D (28.1%) but strains
      susceptible to phage 42D were significantly (P < or = 0.05; X2) more resistant
      (4.2%) to methicillin than those not lysed by the phage (0.0%). Amongst 134
      enterotoxigenic strains, 32 (23.9%), 77 (57.5%), 67 (50.0%) and 21 (15.7%)
      produced staphylococcal enterotoxins A(SEA), B(SEB), C(SEC) and D(SED)
      respectively either alone or mixed. SEB and SEC were significantly (P < or =
      0.01; X2) more produced than either SEA or SED. Strains lysed by groups IV, i.e.
      42D (62.5%), and III (56.7%) were more enterotoxigenic than those sensitive to
      phages in groups II (45.5%) and non-typable (46.2%) but the differences were not
      statistically significant (P > or = 0.05; X2). Strains lysed by group II phages
      (72.7%) were significantly (P < or = 0.05; X2) more resistant to antimicrobial
      agents than those lysed by phage 42D (18.8%). It was concluded that bovine
      mastitis strains of S. aureus in Trinidad were highly susceptible to
      bacteriophages and antimicrobial agents and enterotoxigenic and less than one
      third may be considered to be bovine strains.

PMID- 8553707
TI  - Lipofuscin pigment in cerebellar Purkinje neurones and choroid plexus epithelial
      cells of macaque monkeys with Plasmodium knowlesi cerebral malaria: an electron
      microscopical observation.
AB  - Experimental infection of rhesus monkeys (Macaca mulatta) with a virulent (W1)
      strain of Plasmodium knowlesi resulted in cerebral malaria. Electron
      microscopical examination of the brain revealed large numbers of intracytoplasmic
      lipofuscin pigment deposits in cerebellar Purkinje neurones and choroid plexus
      epithelium of the lateral ventricle. This lesion may be part of the nervous
      system response to ischaemic hypoxia.

PMID- 8553708
TI  - Isolation and characterization of sialodacryoadenitis virus (coronavirus) from
      rats by established cell line LBC.
AB  - The outbreak of sialoadenitis occurred in a laboratory rat colony and the
      causative agent was isolated from the affected salivary glands of diseased rats
      using the established cell line LBC. The isolate readily multiplied, producing
      clear cytopathic effects with syncytium formation, and it was identified
      virologically and serologically as rat sialodacryoadenitis virus. In attempts to
      isolate the virus by primary rat kidney (PRK) cells and suckling mice as well as
      LBC cells, the LBC cells showed higher susceptibility for the virus growth as
      compared with PRK cells or the brain of suckling mice. The isolation rate of
      virus was 100% (5/5) in LBC, 40% (2/5) in PRK cells and 60% (3/5) in suckling
      mice. After four passages in the LBC cells, the virus did not produce disease in
      adult rats, while the mouse brain-passaged virus did.

PMID- 8553709
TI  - Detection and isolation of bovine immunodeficiency-like virus (BIV) in dairy
      herds of Costa Rica.
AB  - Serological (Western blot) detection of bovine immunodeficiency-like virus (BIV)
      in Holstein dairy herds is reported in Costa Rica for the first time, as well as
      the isolation of the virus, from a seropositive bovine, by cocultivation of
      peripheral blood mononuclear cells (PBMC) with embryonic rabbit epithelial (EREp)
      cells. The isolated strain, BIVCR1, reacted similarly in Western blot as the
      reference strain BIV R29 and is clearly distinguishable from bovine leukaemia
      virus (BLV). The data suggest an association between BIV infections and BLV
      infections, as it has been reported elsewhere. From these results it can be
      concluded that BIV is present in Costa Rica and it is suggested that these viral
      infections will probably follow the epidemiological parameters of BLV infections
      in Costa Rica, reaching high infection rates in dairy herds.

PMID- 8553710
TI  - Characterization of a distinct subpopulation of bovine gamma delta T cells.
AB  - A population of mononuclear cytotoxic cells from peripheral blood leucocytes of
      cattle showed no usual markers of B and T lymphocytes. However, it could be
      allocated to a previously unreported gamma delta T cell compartment. This
      assumption was suggested by: 1. The surface expression of CD3; 2. PCR
      amplification of the C delta TcR gene from cDNA; and 3. The detection of
      peripheral blood precursors expressing the workshop cluster (WC) 1 marker of
      bovine gamma delta T cells. These cells are recognized by murine monoclonal
      antibodies (mAbs) 5D4, 1E7, 6F9 and 8D7, raised in the authors' laboratory. The
      above mAbs also identify distinct groups of cells in thymus, spleen, lymph nodes
      and about 1% of uncultured PBL. The most diffuse infiltration of such cells was
      shown in the small intestine, as both intraepithelial and lamina propria
      lymphocytes. Mucosal homing activity was confirmed by immunoperoxidase staining
      on tongue and pharynx sections of healthy cattle.

PMID- 8553711
TI  - Evaluation of different turkey rhinotracheitis viruses used as antigens for
      serological testing following live vaccination and challenge.
AB  - Two enzyme-linked immunosorbent assays (ELISA) developed in the authors'
      laboratory for turkey rhinotracheitis serological testing, a commercial ELISA
      kit, and two virus-neutralization (VN) assays were compared with respect to the
      efficiency of these assays for serological monitoring in specific-pathogen-free
      (SPF) turkeys inoculated with four pathogenic isolates of turkey rhinotracheitis
      virus, with or without previous live vaccination. Both the live vaccine and the
      different isolates of virus were shown to induce antibody rises, the
      detectability of which varied depending on the ELISA or VN assay used for
      serological testing. The results show that 3 weeks after vaccination with an
      attenuated strain, the choice of an inadequate antigen for serological testing
      may be the cause of an apparent lack of immunogenicity of the vaccine, and that 2
      weeks after challenge, such a choice in ELISA can also hinder the early diagnosis
      of a TRT virus infection in both vaccinated and unvaccinated turkeys.

PMID- 8553712
TI  - Comparative RAPD-PCR analysis of lungworms (Dictyocaulidae) from fallow deer,
      cattle, sheep, and horses.
AB  - Genomic DNA isolated from the four Dictyocaulus species D. viviparus, D. eckerti,
      D. filaria and D. arnfieldi was compared by random amplified polymorphic DNA
      polymerase chain reaction (RAPD)-PCR to get additional information whether
      lungworms from fallow deer belong to a separate species (D. eckerti) or have to
      be regarded as an isolate of D. viviparus in wild ruminants. The resulting
      banding patterns of the electrophoresed PCR products were compared to assess the
      degree of genetic differences between the different lungworms. For the two D.
      viviparus isolates a similarity coefficient of 93.4% was calculated, whereas the
      similarity coefficient of D. viviparus, D. eckerti, D. filaria and D. arnfieldi
      ranged from 12% to 32%. The similarity coefficient of 32% between D. eckerti and
      D. viviparus compared with the intraspecies similarity of 93.4% indicates that D.
      eckerti most likely belongs to a separate species and is not a D. viviparus
      isolate of wild ruminants.

PMID- 8553713
TI  - [The characteristics of the functional activity of the liver cells in rabbits
      with an experimental staphylococcal infection].

PMID- 8553714
TI  - [Pasteur and Russian microbiology].

PMID- 8553715
TI  - [The biography of Pasteur].

PMID- 8553716
TI  - [Immunobiological preparations: their present and future].

PMID- 8553717
TI  - [A comparative study of the DNAse activity of leptospirae on solid nutrient
      media].

PMID- 8553718
TI  - [The anniversary of the Moscow G. N. Gabrichevskii Research Institute of
      Epidemiology and Microbiology].

PMID- 8553719
TI  - [An unusual epidemic outbreak of food poisoning in a children's health-promotion
      camp (epidemiological practice No. 4)].

PMID- 8553720
TI  - [An outbreak of intestinal infection of unestablished etiology in a boarding
      school (epidemiological practice No. 5)].

PMID- 8553721
TI  - [An epidemic outbreak of Sonne dysentery in a children's center (a commentary on
      readers' responses)].

PMID- 8553722
TI  - [The growth dynamics and biosynthetic properties of Haemophilus influenza under
      different cultivation conditions].

PMID- 8553723
TI  - [A diphtheria outbreak at a burn center].

PMID- 8553724
TI  - [Monoclonal antibodies in the differentiation of Pseudomonas mallei and
      Pseudomonas pseudomallei].

PMID- 8553725
TI  - [A new nutrient medium for growing a microbial culture of staphylococci].

PMID- 8553726
TI  - [The acid exopolysaccharide of the causative agent of melioidosis].

PMID- 8553727
TI  - [The presence of Staphylococcus aureus and Staphylococcus epidermidis on the skin
      of patients with atopic and seborrheic dermatitis].

PMID- 8553728
TI  - [The selection of a virulent subpopulation of Escherichia coli during Shigella
      and Salmonella infections in children].

PMID- 8553729
TI  - [The use of silica gel-based ion-exchange sorbents for isolating one of the iron
      dependent proteins of meningococci].

PMID- 8553730
TI  - [The use of a cell immobilization technic for the continuous cultivation of toxin
      forming anaerobes].

PMID- 8553731
TI  - [The effect of pectin on the viability of Vibrio cholerae].

PMID- 8553732
TI  - [The effect of Aspergillus flavus metabolites on the development of experimental
      Klebsiella pneumonia].

PMID- 8553733
TI  - [The characteristics of the epidemic process of hepatitis B in Nizhni Novgorod in
      relation to drug addiction].

PMID- 8553734
TI  - [The systematization of leptospirosis foci].

PMID- 8553735
TI  - [The epidemiological division of Krasnoyarsk Territory into tick-borne
      encephalitis regions].

PMID- 8553736
TI  - [The clinico-epidemiological characteristics of trichinelliasis in Karelia].

PMID- 8553738
TI  - [Cholera as a natural-focus sapronotic infection].

PMID- 8553737
TI  - [The development of semicontinuous processes for the cultivation of Haemophilus
      influenzae b].

PMID- 8553739
TI  - [The epidemiological determinants of the irregular territorial spread of typhoid
      fever].

PMID- 8553740
TI  - [A water-borne outbreak of hepatitis A among students employed in agricultural
      operations on a vegetable-growing farm].

PMID- 8553741
TI  - [The importance of examining donor blood in preventing hepatitis C].

PMID- 8553742
TI  - [The spread of hepatitis B and C markers and the etiological structure of the
      morbidity with acute viral hepatitis of the population in the Kuznetsk Basin and
      northwestern Kazakhstan].

PMID- 8553743
TI  - [Antibodies to the hepatitis C virus in Azerbaijan].

PMID- 8553744
TI  - [The serological diagnosis of hepatitis B and D in patients in a general
      hospital].

PMID- 8553745
TI  - [The anthroponotic nature of the epidemic process in salmonellosis in young
      children].

PMID- 8553746
TI  - [The effect of the antigens and strains of Yersinia pestis with the expression of
      different immunogenicity and virulence determinants on the level of lymphocyte
      blast transformation].

PMID- 8553747
TI  - [An evaluation of the intraspecific marking of Klebsiella pneumoniae in the
      epidemiological analysis of a hospital outbreak].

PMID- 8553748
TI  - [Recurrent epidemics: a formal model of the self-regulation of parasitic
      systems].

PMID- 8553749
TI  - [An experimental study of humoral immunity factors in immunization with a cell
      free staphylococcal vaccine].

PMID- 8553750
TI  - [The chemical and immunochemical characteristics of the antigens of Shigella
      dysenteriae 1 isolated by using hydroxylamine hydrochloride].

PMID- 8553751
TI  - [Changes in 5'-nucleotidase activity in the dynamic formation of whooping cough
      immunity].

PMID- 8553752
TI  - [The antigenic and immunogenic properties of the bivalent strain Shigella
      flexneri-Shigella sonnei 1 No. 200].

PMID- 8553753
TI  - [The epidemiological and immunological efficacy of revaccination against
      diphtheria].

PMID- 8553754
TI  - [Autoimmune reactions in rabbits induced by immunization and hyperimmunization].

PMID- 8553755
TI  - [The determination of the duration of postvaccinal immunity against tularemia].

PMID- 8553756
TI  - [An immunoenzyme method for detecting Brucella antibodies and antigen in the
      blood serum of animal breeders from farms with an unfavorable brucellosis
      situation].

PMID- 8553757
TI  - [The effect on Coxsackie B3 viral infection of these different immunomodifiers:
      pertussis corpuscular vaccine, purified staphylococcal anatoxin and their
      combination].

PMID- 8553758
TI  - [The effect of recombinant alfa-2 interferon (reaferon) on the functional
      activity of natural killers in acute viral hepatitis B].

PMID- 8553759
TI  - [The immunomodulating activity of Shigella dysenteriae 1 strains differing by
      their capacity for invasion and Shiga toxin production].

PMID- 8553761
TI  - [The use of an enzymatic hydrolyzate of Chlorella biomass in media for growing
      eukaryotic cells].

PMID- 8553760
TI  - [The effect of thymoptin in the specific immunotherapy of experimental microbial
      allergy].

PMID- 8553762
TI  - [The interferon-inducing activity of biologically active antidyspeptic
      preparations of the gastrointestinal tract and of the replication dsRNA of
      Escherichia coli phage].

PMID- 8553763
TI  - [The effect of an acellular staphylococcal vaccine on the proliferative activity
      of murine lymphocytes].

PMID- 8553764
TI  - [A morphological analysis of the organs of immunogenesis in mice in the dynamics
      of a Salmonella infection].

PMID- 8553765
TI  - [The accumulation in immune lymphocytes of the RNA sequences complementary to the
      gene controlling the synthesis of the corresponding heterologous antigen].

PMID- 8553767
TI  - [The specific proliferative response of the splenic T-cells in mice with opposite
      sensitivity to staphylococcal infection].

PMID- 8553766
TI  - [The participation of Salmonella lipopolysaccharide in the development of
      immunologic deficiency].

PMID- 8553768
TI  - [Antibodies to organ-nonspecific and organ-specific antigens in the blood sera of
      persons with bronchopulmonary diseases].

PMID- 8553769
TI  - [The use of inbred mice for studying the protective properties of Yersinia pestis
      antigens].

PMID- 8553770
TI  - [The sterilization of Antilympholin by a radiation method combined with
      filtration].

PMID- 8553771
TI  - [A comparative evaluation of the use of bacterial and latex phagocytosis objects
      for the study of the phagocytic activity of peripheral blood neutrophils].

PMID- 8553772
TI  - [The use of a method of television microscopic analysis for the rapid
      demonstration of pathogenetic enterobacteria in milk].

PMID- 8553773
TI  - [The development and testing of a latex agglutination reaction for the rapid
      diagnosis of a staphylococcal infection].

PMID- 8553775
TI  - [A comparative study by immunoblotting of the serological response in white mice
      and guinea pigs inoculated against plague].

PMID- 8553774
TI  - [A rapid method of detecting bacteria in the genus Salmonella].

PMID- 8553776
TI  - [The evaluation of alpha-toxin formation in Staphylococcus aureus with different
      methicillin sensitivities].

PMID- 8553777
TI  - [Experience in using immunoenzyme analysis for assessing the carriage of the
      HBsAg of the hepatitis B virus and the postvaccinal immunity in relation to
      whooping cough, diphtheria and tetanus in the population of the Republic of North
      Ossetia].

PMID- 8553778
TI  - [A rapid method for determining the species attribution of bacteria in the genus
      Salmonella by using the polymerase chain reaction and restriction analysis].

PMID- 8553779
TI  - [The development and evaluation of a leptospiral polyvalent antigenic
      erythrocytic diagnostic agent].

PMID- 8553780
TI  - [Solar geomagnetic activity and the biological properties of Staphylococcus
      aureus].

PMID- 8553781
TI  - [The comparative evaluation of methods for the serological diagnosis of
      glanders].

PMID- 8553782
TI  - [The production of hybridomas producing monoclonal antibodies to the causative
      agent of melioidosis by using antigen-stimulated lymphocytes in an in-vitro
      system].

PMID- 8553783
TI  - [A comparative evaluation of the efficacy of immunological methods of diagnosis
      in allergic states in children].

PMID- 8553784
TI  - [The mechanisms of the damaging action of rotaviruses on the intestinal wall].

PMID- 8553785
TI  - [The seasonal dynamics of the blood serum bactericidal activity in healthy
      persons].

PMID- 8553786
TI  - [A new nutrient medium for isolating representatives of the genus
      Bifidobacterium].

PMID- 8553787
TI  - [Intestinal dysbiosis in the population of the Far North].

PMID- 8553788
TI  - [The use of oligostimulin for correcting the intestinal microflora in rats].

PMID- 8553789
TI  - [The characteristics of the liver subcellular structures in rabbits with an
      experimental staphylococcal infection].

PMID- 8553790
TI  - [Is there Kawasaki disease (syndrome) in our country?].

PMID- 8553791
TI  - [Botulism in the Russian Federation (1988-1992)].

PMID- 8553792
TI  - [Physiopathology of cerebellar symptoms: from Holmes to our times].

PMID- 8553793
TI  - The amyloid peptide precursor in Alzheimer's disease.
AB  - beta A4, an hydrophobic peptide containing from 39 to 43 amino acids, is the
      major constituent of the amyloid core of characteristic lesions of Alzheimer's
      disease (AD) known as senile plaques. By cDNA cloning, it was demonstrated that
      beta A4 is derived from a much larger precursor named the amyloid peptide
      precursor or APP. The isolation of cDNA clones and the characterization of their
      nucleotide sequence has shown that several APP proteins containing from 365 to
      770 amino acids are produced by alternative splicing of a single primary
      transcript. The major APP isoforms contain a large extracellular N-terminal
      domain and a short intracellular C-terminal end. The beta A4 sequence itself is
      contained for 15 amino acids in the transmembrane domain while 28 amino acids are
      protruding into the extracellular space. The gene encoding APP is located on
      human chromosome 21, which is involved in the autosomal dominant inheritance of
      some early onset of familial AD (FAD). In a few families, mutations of the APP
      gene have been described. Although they can explain less than 3% of all FAD
      cases, these mutations clearly demonstrate that APP metabolism is involved in the
      development of AD. The overexpression of APP in several cultured cells allowed to
      characterize two catabolic pathways of the protein. A non amyloidogenic pathway
      precludes formation of beta A4, because APP is cleaved by an alpha-secretase
      within the beta A4 sequence, leading to the extracellular release of a C-terminal
      truncated protein. The amyloidogenic pathway produces soluble extracellular beta
      A4, by cleavage of APP by beta- and gamma-secretases after endocytosis of the
      transmembrane protein. Although soluble beta A4 is non toxic, it becomes very
      neurotoxic as soon as it makes fibrils. It is therefore essential to characterize
      the different factors which favor the organization of beta A4 into fibrils. They
      have to be considered as risk factors for AD, as well as targets for new
      therapies. Another therapeutic approach could consist in developing molecules
      able to inhibit beta A4 production by stimulating the non amyloidogenic pathway
      of APP.

PMID- 8553794
TI  - Cervical dystonia (spasmodic torticollis). Some aspects of the natural history.
AB  - A literature survey was done to outline the natural history of cervical dystonia
      (spasmodic torticollis). The disorder starts between 25 and 60 years with head
      deviation or neck pain. Sometimes, there are personal or familial extrapyramidal
      antecedents (tremor, dystonia). The role of a preceding neck or head trauma is
      unsettled. Often, there is a delay in diagnosis of more than one year. The
      majority of patients show steady progression of their focal dystonia and reach
      maximal disability after five years; neck pain occurring in 70-80% contributes
      significantly to disability. In a third of the cases, there is a progression to
      segmental dystonia. In about 20% of the patients a spontaneous, sustained or
      unsustained remission of the torticollis can be observed; this occurs
      particularly in cases with earlier age of onset. Cervical dystonia has important
      psychosocial consequences: many patients have to withdraw from their job or from
      social activities.

PMID- 8553795
TI  - Chronic intrathecal baclofen in severely disabling spasticity: selection,
      clinical assessment and long-term benefit.
AB  - Flexor and extensor spasms associated with severe spasticity frequently cause
      pain and suffering in neurologically impaired patients, and greatly interfere
      with comfort and activities. When high doses of oral medications are necessary to
      keep the symptoms under control and are poorly tolerated, the long-term spinal
      selective intrathecal infusion of baclofen by means of implanted drug pump and
      catheter is a safe, efficient and reversible alternative to destructive surgical
      procedures. Between September 1991 and March 1995, intrathecal baclofen was
      infused in 18 selected patients out of a series of 42 severely disabled spastic
      cases. We report here our preliminary experience with the criteria of selection,
      the initial intrathecal bolus test and the long-term benefit of the selected
      patients. Our results confirm the dramatic immediate and long-term benefit
      reported in other series. After a period of treatment of 1 to 42 months, 13
      patients had a complete disappearance of their spastic symptoms without any oral
      treatment, one patient kept unchanged clonus despite the use of low-dose oral
      treatment and another one a severe, not improved dysuria although in both of them
      hypertonia and spasms were abolished. Finally, 2 patients had important joint
      stiffness slightly impairing the benefit from the treatment. None of the 18
      patients had central side-effects related to baclofen. With time, a slight
      increase in daily dose (inferior to 10%) was necessary in most patients.

PMID- 8553796
TI  - Dissection of the internal carotid artery: aetiology, symptomatology, clinical
      and neurosonological follow-up, and treatment in 60 consecutive cases.
AB  - We reviewed the medical records of 60 consecutive patients (28 men and 32 women;
      aged from 13 to 63 years) with the diagnosis of dissection of the internal
      carotid artery (ICA), and with available clinical and neurosonological follow-up.
      Ten cases occurred after trauma and 50 cases were spontaneous. Angiographic
      evidence of fibromuscular dysplasia of the ICA was found in 23% of the cases.
      Unilateral headaches or neck pain associated with focal cerebral ischemic
      symptoms or oculosympathetic palsy were the most common findings. Less frequent
      symptoms such as isolated cranial nerve palsies and pulsating bruits were also
      observed. Follow-up ranged from 3 to 144 months (mean, 37.5 months). A favourable
      outcome occurred in 73.7% of the cases with a follow-up of 6 months or more, and
      seemed to depend on the severity of the ischemic cerebral deficit associated with
      the ICA dissection. 68% (41/60 cases) of our patients developed stroke and 18%
      (11/60 cases) experienced a transient ischemic attack, which occurred as the
      initial manifestation of the ICA dissection in 28.8% (15/52 cases) of the cases,
      and with a delay (more than 24 hours) in the other cases. Evidence of
      embolization in the cerebral arteries was found in 36% of the cases with stroke
      (15/41 cases). Anticoagulant therapy, given in 34 of our patients, seems to be
      justified by the fact that a considerable risk exists for cerebral emboli in
      association with ICA dissections; no serious neurological complications were
      observed in our series as a result of this anticoagulant therapy. Doppler
      sonography follow-up diagnosed a recanalization in 67.8% of the stenotic or
      occlusive dissections, most of them being completed within the first 6 months
      (92%). Recurrence of ICA dissection is exceptional but occurred in one of our 60
      cases, 2.5 years after the first event.

PMID- 8553797
TI  - Bromocriptine is ineffective in the treatment of chronic nonfluent aphasia.
AB  - The effect of bromocriptine on chronic nonfluent aphasia was investigated in 4
      patients suffering from a stroke 24 to 35 months before the onset of this study
      (average 29 months). Two patients had Broca, one had global and the other
      transcortical motor aphasia. CT-scans demonstrated anterior-posterior infarctions
      in 3 patients and anterior infarction in one. Bromocriptine was given initially
      at a dosage of 10 mg/day, and of 25 mg/day during the follow ups. By means of
      aphasia tests, bromocriptine was found to be ineffective for the treatment of any
      symptoms of chronic nonfluent aphasia.

PMID- 8553798
TI  - Rapidly developing neurological symptoms in a 40-year-old man with AIDS.

PMID- 8553799
TI  - Reversal of multiple spinal MS lesions at MRI: an uncommon observation.

PMID- 8553800
TI  - [Calcified tuberculous abscess of the psoas muscle. Apropos of a case].

PMID- 8553801
TI  - Seafaring: a risk for seamen's oral health?
AB  - Information about the oral status and dental health behavior and the working
      history of 369 Finnish seamen on different types of ships was gathered by means
      of a questionnaire. A control group of workers on shore was formed for sailors 35
      44 years of age. Removable dentures were worn by 16% of the seamen. Oral
      disorders during the week before the study were reported by one-third. During the
      previous 2 years 14% of the sailors had had at least one episode of oral
      troubles, 15% twice and 9% three or even more times. One-third of seamen with
      oral trouble had needed pain-killing tablets or antibiotics. Sick leave days had
      been needed by 3% of respondents during the previous 2 years because of oral
      disorder (mean length of sick leave period was 1.4 days). The control group
      reported gum bleeding more often than the seafarers. Even though there were no
      signs of poorer dental condition in sailors than in the controls on shore, the
      possibility that the seafaring could constitute a risk for the oral health of
      seamen in other age groups cannot be excluded.

PMID- 8553802
TI  - Edentulousness in Iceland in 1990. A national questionnaire survey.
AB  - Levels of edentulousness were established for seven age groups by means of self
      administered questionnaires. The percentage of edentulousness in the Icelandic
      adult population (18 years and over) was 20.7%. Edentulousness was first reported
      in the 35- to 44-year-olds and increased rapidly with age. Women had a higher
      level of edentulousness than men, and the percentage of edentulous people in
      Reykjavik was significantly lower than in towns, villages, and rural areas. The
      proportion of edentulous 35- to 44-year-olds and those 65 years old or older was
      significantly lower than in a similar study in 1985. The percentage of 18- to 79
      year-old edentulous Icelanders in 1990 decreased considerably from the results of
      a national survey on oral health performed in 1962, mainly as a result of a major
      reduction of edentulousness in the younger age groups and among women.

PMID- 8553803
TI  - Mastique laminate veneers: results after 4 and 10 years of service.
AB  - The purpose of the present study was to evaluate the clinical quality over 4
      years and the longevity over 10 years of 77 Mastique laminate veneers (DeTrey,
      Dentsply). The veneers were bonded to incisors and canines with a light-cured
      composite resin, using the acid-etch technique, and examined every 1/2 year in
      accordance with USPHS criteria. Anatomic form and marginal adaptation were rated
      excellent in more than 50% of the veneers throughout the study. Moderate surface
      wear was seen in most of the veneers after 4 years of service. Marginal
      discoloration and color match were recorded as not acceptable in 20% of the
      veneers at the 4-year control. No significant difference was found in the
      gingival index between veneer and control teeth. The cumulative retention rate
      was 40% after 4 years and 20% at the 10-year recall. Owing to the high frequency
      of spontaneous loss, Mastique laminate veneers cannot be recommended as permanent
      restorations.

PMID- 8553804
TI  - Timing of first fillings on different permanent tooth surfaces in Finnish
      schoolchildren.
AB  - The timing of the placement of first fillings because of caries on different
      permanent tooth surfaces was determined at three health centers in Finland. The
      927 subjects analyzed were born either in 1970-71 o4 in 1980-81. Basically, two
      different types of filling placement site were identified: 1) fissures and pits
      and 2) proximal and smooth surfaces. In some fissures and pits a 'post-eruptive'-
      that is, fillings placed in the year of emergence--was observed. This step had
      decreased markedly in the cohort born in 1980-81. The curves plateaued
      (retardation phase) at 50-60% for the occlusal surfaces in first molars for the
      children born in 1970-71 and at 20-30% for the younger cohort. The time without
      any filling varied from 1 to 7 years on smooth surfaces, and some surfaces
      remained totally filling-free. The filling placement curves followed the pattern
      of caries attack and can thus be used as an indicator of dental health.

PMID- 8553805
TI  - The giant cell fibroma. A review of 103 cases with immunohistochemical findings.
AB  - This article reports a series of 103 cases of giant cell fibromas occurring in
      the oral mucosa. The commonest location was the gingiva, followed by the tongue
      and the buccal mucosa. The mean age of the patients was 27.7 years, and the
      median age 21 years. Microscopically, the tumors were characterized by the
      presence of large stellate or angular cells, which occasionally contained several
      nuclei. Immunohistochemical stains showed that the cells were vimentin-positive
      but negative for S-100 protein, cytokeratin, leukocyte common antigen, and
      neurofilament.

PMID- 8553806
TI  - Microscopy and tomography of erosive changes in the temporomandibular joint. An
      autopsy study.
AB  - Thirty-nine temporomandibular joint autopsy specimens were examined by microscopy
      and tomography for erosive changes. We found two types of erosive changes, an
      extensive type with complete loss of cartilage and a local type with retained
      articular cartilage. On microscopic examination nearly twice as many temporal
      components as condyles were eroded. The erosions were generally more extensive in
      the condyle. Erosions in the condyle were evenly distributed. In the temporal
      component there was a slight predominance of erosions located to the lateral part
      of the tubercle. The radiologic investigation underestimated both the presence
      and the extent of the erosions. Positive predictive values and negative
      predictive values were 0.70 and 0.83, respectively, for erosions in the condyle
      and 0.91 and 0.68 for erosions in the temporal component. It is suggested that
      the initial event in osteoarthrosis of the TMJ can occur as a subarticular hard
      tissue change. The need for more accurate diagnostic tools than radiography
      should be stressed.

PMID- 8553807
TI  - Psychologic aspects of patients with symptoms presumed to be caused by
      electricity or visual display units.
AB  - Psychologic factors were studied in 10 patients with symptoms presumed to be
      caused by electricity (EG) and in 10 patients with symptoms presumed to be caused
      by visual display units (VG) and compared with a sex- and age-matched control
      group (CG). Psychologic differences between the EG and VG were also measured. The
      symptoms presumed to be caused by electricity or visual display units were
      registered, and the personality, psychologic functioning, and quality of life
      were determined by using the Karolinska Scales of Personality (KSP), an
      additional Personality Scale (PS), a Psychological Functioning Scale (PFS), and a
      quality of Life Scale (QLS). The results showed that the commonest general
      symptoms in the EG/VG were skin complaints, fatigue, pain, and dizziness, and the
      commonest oral symptoms were gustatory disturbance, burning mouth, and
      temporomandibular joint dysfunction. The patients in the EG described more
      different types of both general and oral symptoms than those in the VG. The
      result showed that the VG scored significantly higher only in the KSP Somatic
      Anxiety and Muscular Tension scales, and the EG scored significantly lower in the
      KSP Socialization scale and significantly higher in the Somatic Anxiety, Muscular
      Tension, and Psychasthenia scales. In addition, only the EG differed
      significantly on the PS, PFS, and QLS. The EG differed significantly in such
      psychologic aspects as being more fatigued in the PS, in having more difficulty
      in concentrating, in taking the initiative, and in getting on with people in the
      PFS and experiencing inactivity and visiting other people rarely in the QLS. The
      conclusion was that patients with symptoms presumed to be caused by electricity
      and visual display units differed from each other psychologically and, therefore,
      should be handled clinically in different ways. The need for an interdisciplinary
      approach to these patients is emphasized.

PMID- 8553808
TI  - Strength and setting behavior of resin-modified glass ionomer cements.
AB  - Diametral tensile strength (DTS), fracture strength, and Vickers microhardness
      were tested in three resin-modified glass ionomer cements (GICs), one chemically
      set GIC, and one dental composite. For the DTS studies test discs were immersed
      in deionized water at 37 degrees C for 10 min, 1 day, and 28 days, respectively.
      Cured discs were also implanted in back muscles of rats for 28 days before
      testing. The effects of light irradiation time and delayed curing on the DTS of
      the cements were also studied. Significantly higher strength was observed in the
      resin-modified GICs in comparison with the chemically set GIC at all observation
      period. K71 showed the highest strength among the GICs. No strength reductions
      were detected after 28 days for the specimens in vivo. An illumination time of 20
      sec was enough to obtain final strength in the PFA and K71 specimens, and 40 sec
      was needed in the VI specimens. The strength of the resin-modified GICs when
      light-cured was significantly higher than when the same cements were allowed to
      set without irradiation. The microhardness of the light-cured GICs was similar to
      that of the dental composite. Considering the improved fracture strength and
      surface hardness, it was concluded that the resin-modified GICs present an
      interesting material for further development.

PMID- 8553809
TI  - Need and demand for dental treatment. A comparison between an evaluation based on
      an epidemiologic study of 35-, 50-, and 65-year-olds and performed dental
      treatment of matched age groups.
AB  - The aim of this study was to compare the results of the level of treatment need
      as judged from a sample drawn from the general population aged 35, 50, and 65
      years with treatments performed in 1992 and 1993 of patients of matched ages.
      Both the sample and the patients lived in Vasterbotten in the northern part of
      Sweden. In all three age groups there was a significantly higher frequency of
      restorative treatment performed than the professionally assessed need in the
      epidemiologic sample. In all ages examined, treatment aimed at rehabilitation of
      temporomandibular disorders was performed statistically significantly (p < 0.001)
      less frequently than the evaluated need in the population. A similar result was
      found for dentures among 65-year-olds. The results may reflect dental care
      paradigms favoring operations on single teeth rather than treatments aimed at
      functional rehabilitation on a broader sense.

PMID- 8553810
TI  - Ceramic inlays (Cerec) cemented with either a dual-cured or a chemically cured
      composite resin luting agent. A 2-year clinical study.
AB  - On the basis of the criteria of the California Dental Association (CDA), 66
      CAD/CAM-manufactured ceramic class-II inlays (Cerec) were compared
      intraindividually after they had been cemented with either a chemically cured or
      a dual-cured composite resin luting agent in 27 patients. Plaque and gingival
      conditions, the overall time consumption for producing each inlay, and the
      frequency of postoperative sensitivity were also evaluated. There was no
      statistically significant difference between the two luting agents with regard to
      the properties evaluated. One inlay was replaced owing to fracture of the
      restored tooth just before the 24-month re-examination. After 2 years excellent
      CDA ratings were obtained for color in 92% of the remaining 65 inlays. The
      corresponding figures for surface and for anatomic form were 100% and 85%,
      respectively. For margin integrity 85% of the 33 inlays cemented with the dual
      cured luting agent and 88% of the 33 inlays cemented with the chemically cured
      luting agent were rated excellent after 2 years.

PMID- 8553811
TI  - A 2-year follow-up study of incisal tooth wear in dental students.
AB  - This report was derived from cross-sectional and longitudinal analyses of
      prevalence, pattern, and severity of incisal wear in 64 dental students who had
      virtually complete dentitions at the first examination and unchanged dentitions
      at the re-examination. They were first examined in 1991 and re-examined after 24
      months in 1993. The average age of the students in 1991 was 23 +/- 1.7 years.
      Assessment of incisal wear was made on stone casts based on silicone impression
      material in accordance with the Incisal wear Index (IwI). The results showed that
      the prevalence of incisal wear had not changed during the observation period. The
      severity of incisal wear for maxillary and mandibular central and lateral
      incisors had remained essentially the same, whereas the severity of wear of
      maxillary and mandibular canines had increased during the observation period.
      There was no statistically significant relationship between age and IwI. The wear
      pattern found for anterior teeth is discussed in relation to the cuspid
      protection and the group function theories of occlusion.

PMID- 8553812
TI  - Evaluation of in vitro properties of films of saliva substitutes in contact with
      different surfaces. A comparative study with instruments for measurements of
      friction and rheologic properties.
AB  - An instrument based on friction measurement has been developed to evaluate oral
      mucosal dryness objectively. The purpose of this study was to compare the
      friction instrument with instruments measuring in vitro rheologic properties.
      Measurements were performed against steel and irreversible hydrocolloid after
      application of different concentrations of aqueous solutions of
      carboxymethylcellulose and chitosan lactate. The results of the measurements were
      logical, with inversely proportional values for the friction instrument as
      compared with values obtained using the instrument measuring rheologic
      properties; that is, increased viscosity led to decreased friction values.

PMID- 8553813
TI  - Early revision among 12,179 hip prostheses. A comparison of 10 different brands
      reported to the Norwegian Arthroplasty Register, 1987-1993.
AB  - On the basis of data from the Norwegian Arthroplasty Register during the period
      1987-1993, we have compared times to revision for 10 different cemented total hip
      prostheses. A total of 11,169 patients, with 12,179 primary total hip
      replacements (THRs), performed with high viscosity cement for primary arthrosis
      and followed for a maximum of 6.4 years, were included in this study. The Kaplan
      Meier estimate of the overall percentage revised after 5 years was 2.5 (95%
      Confidence Interval: 2.1-3.0). For the Charnley prosthesis (n 6,694), 2.9% were
      revised after 5 years (95% CI: 2.3-3.4). Using Cox regression to adjust for
      gender, age, type of cement and use of systemic antibiotic prophylaxis, the
      Charnley prosthesis was compared with the 9 other brands. The revision rate for
      the Spectron/ITH combination (Spectron acetabulum, ITH femur) (n 1,034) was only
      0.35 (p 0.04) times that of the Charnley prostheses. The Elite/Charnley
      combination (Elite acetabulum, Charnley femur) (n 507) and the Muller Type
      prosthesis (n 116) showed poorer results with failure rates 2.3 (p 0.01) and 2.7
      times (p 0.04) that of Charnley, respectively. Although the overall results for
      cemented THRs in general were good, clinically important differences in revision
      rates were demonstrated among the cemented prosthesis brands. Our findings
      underline the need for careful evaluation of different total hip replacements.

PMID- 8553814
TI  - Revision for aseptic loosening of uncemented cups in 4,352 primary total hip
      prostheses. A report from the Norwegian Arthroplasty Register.
AB  - From September 1987 until January 1994 the Norwegian Arthroplasty Register
      recorded 5,021 primary total hip replacements performed with uncemented
      acetabular components. We compared the survival until revision for aseptic
      loosening of the cup, in the 11 commonest types (n 4,352). The overall cumulative
      revision rate for the acetabular components was 3.2% after 5 years and 7.1% after
      6 years, with large differences among the designs. With the hydroxyapatite (HA)
      coated cups and the hemispheric porous-coated cups, the failure rate was less
      than 0.1%. Of the unthreaded hemispheric porous-coated cups, Harris-Galante and
      Gemini (n 626), none had been revised, and of the HA-coated cups, Atoll and
      Tropic (n 1,943), only 1 had been revised. For the threaded uncoated metal-backed
      cups, the results varied from no revisions of the PM cups (n 148) to a cumulative
      6-year revision rate of 21% for the Ti-Fit (n 300). The all-polyethylene Endler
      cups (n 334) had a cumulative revision rate of 14%. Women and patients with
      inflammatory arthritis had poorer results. However, the type and the design of
      the cups were of far greater importance for the results than patient-related
      factors.

PMID- 8553815
TI  - Wear of the polyethylene acetabular cup. The effect of head material, head
      diameter, and cup thickness studied with a hip simulator.
AB  - Ultra-high molecular weight polyethylene acetabular cups backed by Ti-6Al-4V
      acetabular shells were articulated against Co-Cr-Mo alloy, ion-implanted Co-Cr-Mo
      alloy, and zirconia ceramic femoral heads in a hip joint simulator. Three tests
      of three million walking cycles each were run with five different head-cup
      combinations. The wear of the cups was measured gravimetrically at half a million
      cycle intervals. When the thickness of the cup was 10.9 mm, the mean wear rate
      was 0.14 mm/year against 28 mm dia. Co-Cr-Mo heads and 0.09 mm/year against ion
      implanted 28 mm Co-Cr-Mo heads. When the thickness of the cup was 7.0 mm, the
      mean wear rate was 0.04 mm/year against 28 mm zirconia heads, but when the
      thickness was 10.9 mm, no wear occurred against 28 and 32 mm zirconia heads. The
      results indicate that a significant reduction in the wear of the polyethylene cup
      can be expected if zirconia is used as the head material, instead of Co-Cr-Mo
      alloy or ion-implanted Co-Cr-Mo alloy. The diameter of the zirconia head, 28 vs.
      32 mm, seems unimportant, but a cup thickness much below 10 mm may be
      disadvantageous.

PMID- 8553816
TI  - Fixation of femoral neck fracture. A randomized 2-year follow-up study of hook
      pins and sliding screw plate in 222 patients.
AB  - We compared fixation with hook pins or sliding screw plate in a prospective
      randomized study of 222 patients with a cervical hip fracture. Radiographic
      evidence of early redisplacement, nonunion, or late segmental collapse was found
      in 43 of 122 patients operated on with two hook pins and in 40 of 100 patients
      operated on with the sliding screw plate. According to the actuarial method, the
      failure rate after 2 years was 38% with hook pins and 46% with screw plates,
      which not is a significant difference. Due to early redisplacement, reoperation
      with an endoprosthesis was performed within 0.5 (2) years in 11 (22) patients in
      the hook-pin group and in 4 (17) patients in the sliding-screw plate group.

PMID- 8553817
TI  - Slipped capital femoral epiphysis in 6 of 8 first-degree relatives.

PMID- 8553818
TI  - Changes in bone mineral density of the proximal tibia after uncemented total knee
      arthroplasty. A 3-year follow-up of 25 knees.
AB  - We measured bone remodeling of the proximal tibia prospectively for 3 years after
      uncemented total knee arthroplasty (TKA) in 25 knees with primary arthrosis. In
      the trabecular bone below the tibial component, bone mineral density (BMD) was
      measured in 6 different regions of interest (ROI), using dual photon
      absorptiometry (DPA). In the tibial condyles, where the change in knee alignment
      indicated that the load was reduced postoperatively, a fast bone loss of 7-20%
      was seen during the first 6 months after surgery. A small, but significant
      increase in BMD of 2-7% was seen in the tibial condyles, where the load was
      increased. On average, the density for all ROI below the tibial component showed
      a significant and progressive decrease in BMD, reaching 22% at 3 years follow-up.

PMID- 8553819
TI  - Peroneus longus and tibialis anterior muscle activity in the stance phase. A
      quantified electromyographic study of 10 controls and 25 patients with chronic
      ankle instability.
AB  - The electromyographic activity of the peroneus longus and anterior tibial muscles
      of 25 patients with chronic ankle instability (18 patients with bilateral
      symptoms and 7 patients with unilateral complaints) and 10 controls was
      registered during the stance phase under different walking conditions. With
      balance secured by external support, there was a variable amount of peroneal
      activity, most of which was found in the third quarter of stance. A high increase
      in peroneus longus activity starting after foot-flat was found when subjects had
      to maintain balance in a natural way. No difference in peroneal activity was
      found in relation to instability complaints. It is thought that the peroneus
      longus serves to maintain balance, that this function decreases with increase of
      speed and that one cannot rely on this muscle to prevent an inversion injury
      during normal walking. The anterior tibial muscle was predominantly active in the
      first quarter after heel contact. An increase in activity in the second quarter
      as an effect of loss of secured balance suggests that this muscle plays some part
      in balance control, but this is not its main function. A significant increase in
      tibialis anterior activity was found in patients with bilateral instability. No
      significant difference was found between the symptomatic and asymptomatic leg of
      patients with unilateral instability under the same walking conditions. These
      findings suggest changes in central control.

PMID- 8553820
TI  - Malleolar fractures in alcoholics treated with biodegradable internal fixation.
      6/16 reoperations in a randomized study.
AB  - 29 alcohol abusers with displaced malleolar fractures were randomized to
      treatment with biodegradable self-reinforced polyglycolide screws or metallic
      implants. During an average follow-up time of 7 (0-15) months, 8 patients out of
      16 treated with biodegradable fixation had postoperative redisplacement of the
      fracture and 6 were reoperated. 1 fracture in 13 patients with metallic fixation
      had a slight displacement postoperatively which did not require reoperation.

PMID- 8553821
TI  - Treatment of acute ankle sprain. Comparison of a semi-rigid ankle brace and
      compression bandage in 73 patients.
AB  - We randomized 73 patients with grades II and III ankle sprain to treatment with
      an Air-Stirrup ankle brace or a compression bandage. All patients were instructed
      to attempt early motion and weight bearing when comfortable. Ankle function was
      evaluated after 3-5 days and 2, 4, and 10 weeks with a clinical examination, the
      Sickness Impact Profile questionnaire, Karlsson's scoring scale and recording of
      sick leaves. The group treated with the Air-Stirrup ankle brace was more mobile
      in the initial phase of rehabilitation and had a shorter sick leave. Ankle brace
      treatment resulted in socioeconomic savings.

PMID- 8553822
TI  - Estimation of spinal bone density using conventional MRI. Comparison between MRI
      and DXA in 32 subjects.
AB  - We evaluated the usefulness of MRI T1 and T2 relaxation times in assessing bone
      mineral status. T1 and T2 relaxation times of L3 were measured in 16 pairs of
      identical twins (24 men, 8 women), aged 25-69 years. Bone mineral density (BMD),
      bone mineral content (BMC) and apparent volumetric bone mineral density (BMDvol)
      of L3 were measured from the same subjects using dual x-ray absorptiometry (DXA).
      T2 relaxation time correlated inversely with BMD and BMC (r -0.40 and r -0.47,
      respectively), whereas a significant positive correlation between T1 relaxation
      time and BMDvol was found (r 0.36). The measurement of T1 may give some
      information on bone mineral status in clinical MRI measurements when DXA is not
      available. It is possible that T1 and T2 reflect not only bone density, but also
      other factors related to bone structure.

PMID- 8553823
TI  - Glenoplasty for recurrent posterior shoulder instability. Good results in 13
      cases followed for 1-16 years.
AB  - After the failure of closed treatment, 13 shoulders in 10 patients with chronic
      posterior shoulder instability had an open wedge osteotomy of the collum
      scapulae, with interposition of an autologous graft from the iliac crest. After a
      median follow-up of 9 (1-16) years, there were no recurrent posterior luxations
      or signs of instability. All patients were satisfied, but 3 had slight pain after
      strenuous work. All had a full range of motion.

PMID- 8553824
TI  - Extensor carpi ulnaris syndrome. Findings in 43 patients.

PMID- 8553825
TI  - Evaluation of chronic wrist pain. Arthroscopy superior to arthrography:
      comparison in 39 patients.
AB  - 39 patients with chronic wrist pain underwent arthrography and arthroscopy to
      reveal disruptions of the triangular fibrocartilage complex (TFCC) and/or
      interosseous ligaments. TFCC disruption was diagnosed arthroscopically in 15
      cases of which arthrography revealed the disruption in only 7. In 3 other
      patients, arthrography showed rupture of the TFCC: however, arthroscopy showed no
      defects. Rupture of an interosseous ligament was diagnosed arthroscopically in 6
      patients in all of whom it was also revealed by arthrography. In 6 other
      patients, arthrography showed disruption of an interosseous ligament not verified
      by arthroscopy. We conclude that arthroscopy is superior to arthrography for
      diagnosing chronic wrist pain.

PMID- 8553826
TI  - Exogenous fibroblast growth factors-1 and -2 do not accelerate fracture healing
      in the rabbit.
AB  - Both fibroblast growth factors-1 (acidic FGF) and -2 (basic FGF) increase the
      proliferation of osteoblasts and chondrocytes in vitro and FGF-2 stimulates
      angiogenesis and bone formation in vivo. To test their effects on rabbit tibial
      fracture-healing under stable and unstable mechanical conditions, 3 micrograms of
      either FGF-1 or FGF-2 was injected around rabbit tibial fractures on day 4 after
      fracture. Neither growth factor had a significant effect on either the size of,
      or the amounts of bone and cartilage in, the 10-day callus irrespective of the
      mechanical conditions under which the fracture was healing. The 10-day FGF-2
      treated calluses were, however, more mature than FGF-1-treated calluses because
      the cartilage was separated from the periosteum by bone and endochondral
      ossification had progressed further. In conclusion, the application of FGF-1 or
      FGF-2 to normally healing fractures of the rabbit tibia does not have a
      significant effect on the rate of healing.

PMID- 8553827
TI  - Culture of chondrocytes in alginate and collagen carrier gels.
AB  - In this in vitro study, we compared the potential of collagen and alginate gels
      as carriers for chondrocyte transplantation and we studied the influence of
      demineralized bone matrix (DBM) on chondrocytes in the gels. Chondrocytes were
      assessed for cell viability, phenotype (histology), proliferation rate and
      sulfate incorporation. Collagen gels showed a significant increase in cell
      numbers, but the chondrocytes dedifferentiated into fibroblast-like cells from
      day 6 onwards. In alginate gels, initial cell loss was found, but the cells
      maintained their typical chondrocyte phenotype. Although the total quantity of
      proteoglycans initially synthesized per cell in collagen gel was significantly
      higher, expressed per cell, the quantity in alginate gel eventually surpassed
      collagen. No effects of culturing chondrocytes in combination with DBM could be
      demonstrated on cell proliferation and sulfate incorporation. The collagen and
      alginate gels have different advantages as carriers for chondrocyte
      transplantation. The high proliferation rate of chondrocytes in collagen gel may
      be an advantage, but the preservation of the chondrocyte phenotype and the
      gradually increasing proteoglycan synthesis in alginate gel is a promising method
      for creating a hyaline cartilage implant in vitro.

PMID- 8553828
TI  - Osteogenesis in xenogeneic bone transplantation, using an immunosuppressant.
      Rabbit-rat experiments.
AB  - We investigated osteogenesis and lymphocyte subsets in xenogeneic bone
      transplantation, using the immunosuppressant FK506 (FK). Iliac bones of rabbits
      were transplanted as fresh and frozen xenogeneic bone grafts into an
      intramuscular pouch of rats. FK was injected intramuscularly in half of the rats
      in a dose of 3 mg/kg/day for 14 days after transplantation. At 2, 4, and 8 weeks,
      transplanted grafts and the lymphocyte subsets of these rats were examined. In
      the group not given FK, the grafted bone became necrotic and infiltrated with
      small round cells around the trabeculae. In the FK group, at 2 and 4 weeks, new
      bone was formed in the fresh xenografts without infiltration of lymphocytes. At 8
      weeks, the new bone became necrotic and lymphocytes were present. The percentage
      of T cells (CD 5), B cells and the ratio of CD 4 cells/CD 8 cells were smaller in
      the FK group. Using an immunosuppressant we concluded that xenogeneic bone has an
      osteogeneic potency.

PMID- 8553829
TI  - Survival after pulmonary metastasectomy in soft tissue sarcoma. Prognostic
      factors in 214 patients.
AB  - This retrospective study examines prognostic factors for post-metastasectomy
      survival in soft tissue sarcoma patients. Between 1976 and 1992, 274 consecutive
      patients (median age 49 [7-96] years) with pulmonary metastatic soft tissue
      sarcoma of the extremity or trunk wall (31 at presentation) were managed at the
      Mayo Clinic. 214 underwent pulmonary metastasectomy and 163 of these also
      received adjuvant chemotherapy. There were 195 local excisions, 14 lobectomies,
      and 5 pneumonectomies. 90 patients had solitary metastases, 184 patients had 2 or
      more metastases. 31% of patients had MFH tumors and 88% of all tumors were high
      grade. Median follow-up for survivors was 8 (2-21) years. 5-year overall survival
      after metastasectomy was approximately 40% (cf. 20% for non-metastasectomy). Age
      > 50, MFH tumors, > or = 2 metastases, metastasis size > 2 cm, metastasis-free
      period < or = 18 months, and the use of adjuvant chemotherapy were univariately
      unfavorable factors. Size of metastasis > 2 cm, number of metastases > or = 2,
      and metastasis-free interval < or = 18 months were independently unfavorable for
      survival. In a prognostic system, patients with 0 risk factors had a 60% 5-year
      survival, those with 1, 2, or 3 of these factors had 30%, 20% and 0% survival,
      respectively.

PMID- 8553830
TI  - Osteitis pubis. A case of successful treatment with anticoagulants.

PMID- 8553831
TI  - Autogenous grafting for an osteochondral fracture of the femoral condyle. A case
      report.
AB  - A 16-year-old boy with an osteochondral fracture in the lateral femoral condyle
      was operated on 3 months postinjury with a graft from the non-weight-bearing area
      of the same condyle. After 10 years, the knee was painfree and the range of
      motion was normal.

PMID- 8553832
TI  - Polylactic acid pins.

PMID- 8553833
TI  - Molecular markers for joint and skeletal diseases. An Eric K. Fernstrom
      symposium. Proceedings.

PMID- 8553834
TI  - Osteoarthritis and molecular markers. A rheumatologist's perspective.

PMID- 8553835
TI  - Rheumatoid arthritis--changing theories and treatment modalities.

PMID- 8553836
TI  - Keratan sulfate in body fluids in joint disease.

PMID- 8553837
TI  - Changes in chondroitin sulphate structure induced by joint disease.

PMID- 8553838
TI  - High levels of aggrecan aggregate components are present in synovial fluids from
      human knee joints with chronic injury or osteoarthrosis.

PMID- 8553839
TI  - Hyaluronan in inflammatory joint disease.

PMID- 8553840
TI  - Anabolic and catabolic markers of proteoglycan metabolism in osteoarthritis.

PMID- 8553841
TI  - Upregulation of type X collagen expression in osteoarthritic cartilage.

PMID- 8553842
TI  - Detection and monitoring of progressive degeneration of osteoarthritic cartilage
      by MRI.

PMID- 8553843
TI  - Dynamics of articular joints visualised by MRI: joint flexion, cartilage
      compression and solute-perfusion.

PMID- 8553844
TI  - Role of biochemical markers in assessment of osteoporosis.

PMID- 8553845
TI  - Diagnostic approaches to connective tissue diseases.

PMID- 8553846
TI  - The specificity of collagen cross-links as markers of bone and connective tissue
      degradation.

PMID- 8553847
TI  - Collagen crosslinks in metabolic bone disease.

PMID- 8553848
TI  - Biochemical markers of bone turnover.

PMID- 8553849
TI  - Collagen propeptides as indicators of collagen assembly.

PMID- 8553850
TI  - The tartrate-resistant purple acid phosphatase of bone osteoclasts--a protein
      phosphatase with multivalent substrate specificity and regulation.

PMID- 8553851
TI  - The spatial and temporal expression of cartilage matrix protein illustrates the
      molecular heterogeneity of cartilage.

PMID- 8553852
TI  - Bone changes in metabolic bone disease.

PMID- 8553853
TI  - Validating markers in osteoarthritis.

PMID- 8553854
TI  - Fractures in the elderly.

PMID- 8553855
TI  - Molecular markers for joint and skeletal diseases. Notes from the general
      discussion.

PMID- 8553856
TI  - Chondroitin sulphation in human joint tissues varies with age, zone and
      topography.

PMID- 8553857
TI  - Pathways of aggrecan processing in joint tissues. Implications for disease
      mechanism and monitoring.

PMID- 8553858
TI  - Kinetics of release of aggrecan from explant cultures of bovine cartilage from
      different sources and from animals of different ages.

PMID- 8553860
TI  - Stimulation of bone resorption by the kallikrein-kinin system and the coagulation
      cascade.

PMID- 8553859
TI  - Cartilage degradation and associated changes in biochemical and electromechanical
      properties.

PMID- 8553861
TI  - Cartilage-derived morphogenetic proteins. Key regulators in chondrocyte
      differentiation?

PMID- 8553862
TI  - Matrix metalloproteinases and their inhibitors.

PMID- 8553863
TI  - Osteoarthrosis--the orthopedic surgeon's perspective.

PMID- 8553864
TI  - Antisera and cDNA probes to human and certain animal model bone matrix
      noncollagenous proteins.

PMID- 8553865
TI  - Molecular mechanisms of bone resorption. An update.

PMID- 8553866
TI  - Differential release of molecular markers in joint disease.

PMID- 8553867
TI  - The role of molecular markers to monitor disease, intervention and cartilage
      breakdown in osteoarthritis.

PMID- 8553868
TI  - Collagen II turnover in joint diseases.

PMID- 8553869
TI  - Aggrecan degradation in osteoarthritis and rheumatoid arthritis.

PMID- 8553870
TI  - MMP-8 (neutrophil collagenase) mRNA and aggrecanase cleavage products are present
      in normal and osteoarthritic human articular cartilage.

PMID- 8553871
TI  - Muscle fibre type and dimension in genetically obese and lean Zucker rats.
AB  - Skeletal muscle structure and morphology may be altered in obesity. To study this
      further, muscles from six genetically obese (fa/fa) and six normal male rats were
      examined at 15 weeks of age. The gluteus medius, vastus lateralis and rectus
      abdominis muscles were dissected out and stained for histochemical fibre typing.
      In addition the fibre cross-sectional area was measured on a graphic tablet. The
      proportion of fast-twitch fibres was larger in the vastus lateralis and rectus
      abdominis muscles of the obese rats (P < 0.01); no difference was seen for the
      gluteus medius muscle. For the normal rats the cross-sectional area of the fast
      twitch fibres was 2-3 times larger than the area of slow-twitch fibres in the
      same muscle. The cross-sectional area of the fast-twitch fibres in the obese rats
      was 40-47% less than in the control animals (P < 0.003), while no difference
      between the two groups was found for the slow-twitch fibre area. The data thus
      suggest that in the genetically obese rats the development of fast-twitch fibres
      was primarily affected. Moreover, in these animals some muscles may be more
      affected than others.

PMID- 8553872
TI  - Index of the oxidative potential in human quadriceps muscle: simultaneous
      measurements of [31P]NMR and oxygen consumption during exercise.

PMID- 8553873
TI  - Metabolic and mechanical aspects of foot landing type, forefoot and rearfoot
      strike, in human running.
AB  - The study was undertaken to assess the metabolic and the mechanical aspects of
      two different foot strike patterns in running, i.e. forefoot and rearfoot
      striking (FFS and RFS), and to understand whether there is some advantage for a
      runner to use one or the other of the two landing styles. Eight subjects
      performed two series of runs (FFS and RFS) on a treadmill at an average speed of
      2.50, 2.78, 3.06, 3.33, 3.61, 3.89, 4.17 m s-1. Step frequency, oxygen uptake,
      mechanical work, and its two components, external and internal, were measured. No
      differences were found for step frequency, mechanical internal work per unit time
      and oxygen uptake, while external and total mechanical work per unit time were
      significantly higher, 7-12%, for FFS. The higher external work was the result of
      an increase of the work performed against both gravitational and inertial forces.
      As the energy expenditure was the same it has been speculated that a higher
      storage and release of energy takes place in the elastic structures of the lower
      leg with FFS. In a different series of experiments on six subjects contact time,
      time of deceleration and time of acceleration were measured by means of a video
      camera while running on the treadmill at 2.50, 3.33 and 4.17 m s-1, both FFS and
      RFS. Time of deceleration is similar for FFS and RFS, but contact time and time
      of acceleration are shorter, respectively 12 and 25%, for FFS.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8553874
TI  - Vasostatins, N-terminal products of chromogranin A, are released from the
      stimulated calf spleen in vitro.
AB  - Vasostatins are the N-terminal chromogranin A peptides 7 approximately 22 kDa.
      They have been shown to be present in several endocrine tissues and exhibit
      vasoinhibitory activity in vitro. In a first series of experiments, we
      investigated the presence and subcellular localization of vasostatins in the
      bovine splenic nerve. Experimental results, obtained using gradient
      centrifugation, showed that noradrenaline was enriched 25-fold in the large dense
      core vesicle fraction, compared with the original homogenate. In the latter
      fraction, the 7 and 18 kDa peptides were observed following immunodetection with
      antiserum to chromogranin A1-40 and laser densitometric scanning revealed these
      two fragments as the major N-terminal fragments. Subsequently, we examined the
      release of the 7 and 18 kDa peptides from perfused calf spleen during veratridine
      (20 microM) or 1,1-dimethyl-4-phenylpiperazinium iodide (20 microM) stimulation.
      In the prestimulation samples, we were not able to detect these peptides,
      however, following stimulation, the 7 and 18 kDa chromogranin A fragments became
      apparent. The vasostatin-immunoreactivity, in both bovine chromaffin granule
      lysate and calf spleen perfusate, elutes at the same retention time on reversed
      phase high performance liquid chromatography. The present study demonstrated that
      vasostatins are present in the large dense core vesicles of sympathetic axons and
      are released from the nerve terminals in response to stimulation. The release of
      vasostatins from sympathetic nerves in the spleen suggest an in vivo function for
      N-terminal chromogranin A products of neuronal origin.

PMID- 8553875
TI  - Sympathetic nervous system effects on feline bladder wall compliance throughout
      continence.
AB  - The urinary bladder is a compliant organ, high compliance being essential for
      useful urine storage. The extent to which the sympathetic nervous system promotes
      the storage of urine by increasing bladder compliance is unclear. The aim of the
      present study was to determine the range of bladder volumes over which the
      sympathetic nervous system increased bladder wall compliance. In supine,
      anaesthetized cats, the bladder was filled at twice the rate of natural filling,
      the continence cycle being interrupted at five stages. These stages were when the
      bladder had become globular, during prodromal contractions, soon after non
      micturating contractions had commenced, approximately two-thirds of the way
      through the continence cycle and just prior to micturition. During each of these
      interruptions, bladder volume was held constant while pelvic nerve afferent
      activity and bladder pressure were recorded. Recordings were obtained before and
      during the intravenous infusion of trimethaphan, the resulting partial ganglion
      blockade decreasing arterial pressure by a third. Bladder pressure as well as
      afferent nerve activity increased significantly when the sympathetic drive was
      transiently blocked, indicating that there had been a prevailing net sympatho
      inhibitory effect promoting bladder wall relaxation. This effect was observed
      during prodromal contractions and continued until the onset of micturition. This
      net sympatho-inhibitory effect is a potential therapeutic path for the treatment
      of bladder storage disorders.

PMID- 8553876
TI  - Central blood volume influences sympathetic sudomotor nerve traffic in warm
      humans.
AB  - The objective of this study was to test whether changes in central blood volume
      can induce reflex effects on sweating. Multi-unit skin sympathetic nerve activity
      (SSA) was recorded from the posterior cutaneous nerve of the forearm or radial
      nerve branches in 11 healthy volunteers. Skin electrical resistance and skin
      blood flow were recorded in the area innervated by the impaled nerve fascicle.
      Sudomotor nerve traffic and sweating was induced by whole body heating. Lower
      body negative pressure (LBNP) and tilting (30 degrees head up) was used for blood
      volume displacement from the chest to the lower body. Low levels of LBNP (5 and
      10 mmHg) had no effect on blood pressure, heart rate or skin blood flow but
      induced a prompt inhibition of SSA and a reduced number of transient skin
      resistance changes (n = 9), both rapidly returning to control levels after
      cessation of LBNP. Quantitatively, the effect was similar at both levels of LBNP.
      Head up tilting also reduced SSA (n = 3, 19 tilt manoeuvres). A capacity for
      mental stress-induced SSA increase remained during LBNP. Spontaneous fluctuations
      in blood pressure did not affect SSA, arguing against arterial (high-pressure)
      baroreceptors modulating SSA. Consequently, the present results indicate that
      unloading of cardiopulmonary (low-pressure) volume receptors reduces sympathetic
      sudomotor nerve traffic and sweating in warm subjects. It is suggested that the
      reflex contributes to counteracting hypovolaemia.

PMID- 8553877
TI  - Effect of BQ123 on vasoconstriction as a result of either hypoxia or endothelin-1
      in perfused rat lungs.
AB  - A possible role of endothelin (ET)-1 in mediating hypoxic pulmonary
      vasoconstriction (HPV) was examined by comparing haemodynamic differences between
      ET-1-induced vasoconstriction and HPV in isolated perfused rat lungs. An ETA
      receptor antagonist (BQ123) was also employed to assess the effects of ET-1. The
      pulmonary arterial pressure (Ppa) was significantly increased by alveolar hypoxia
      (3% O2) and by ET-1 (5 nM). The pulmonary microvascular pressure was not changed
      by hypoxia, but increased more than two-fold by ET-1 (P < 0.01). Hypoxia
      significantly increased pulmonary arterial resistance (P < 0.01) while ET-1
      significantly increased pulmonary venous resistance (P < 0.01), and slightly
      increased arterial resistance. Lung weight was increased by ET-1 and decreased by
      hypoxia, accompanied by similar Ppa responses in both cases. BQ123 (10(-6) M and
      10(-5) M) did not influence the changes in Ppa and lung weight induced by hypoxia
      or angiotensin II (0.3 micrograms). BQ123 did, however, suppress (P < 0.05) the
      increase in Ppa and lung weight induced by 5 nM ET-1. Thus, it appears unlikely
      that ET-1 is involved in changes in pulmonary vascular tone during acute HPV.

PMID- 8553878
TI  - The insulin secretory response to intravenous glucose in the rat is independent
      of NO formation.
AB  - In isolated pancreative beta cells from rats the insulin secretory response to
      glucose is amplified by L-arginine. Since this effect is inhibited by NO
      synthesis inhibitors, and since L-arginine is precursor of NO, the observation
      indicates a role for NO in insulin secretion from beta cells. We recently
      reported that i.v. L-arginine elicited insulin secretion in anaesthetized rats by
      a mechanism that was partly NO dependent. The aim of the present study was to
      assess if the insulin secretory response to an intravenous infusion of glucose
      also requires an intact NO formation. Anaesthetized rats were given D-glucose
      (100 mg kg-1 min-1 i.v. for 30 min). Plasma insulin (PI), blood glucose (BG)
      levels and mean arterial blood pressure (MAP) were assessed from before and until
      15 min after the end of the infusion. One group of rats were untreated and served
      as controls. The two other groups were pretreated with either of the NO synthase
      inhibitors NW-nitro-L-arginine methyl ester (L-NAME, 50 mg kg-1 i.v.), or NG
      monomethyl-L-arginine (L-NMMA, 100 mg kg-1 i.v.). In controls infusion of glucose
      elevated PI by up to 25 +/- 3 U L-1, and BG by up to 27 +/- 1 mmol L-1.
      Pretreatment with L-NAME elevated MAP from 74 +/- 6 to 132 +/- 4 mmHg, indicating
      that NO synthase was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8553879
TI  - Measurement of the total concentration of functional Na+, K(+)-pumps in rumen
      epithelium.
AB  - Using the technique of vanadate-facilitated [3H]ouabain binding we have developed
      a simple and reliable assay for measuring the concentration of [3H]ouabain
      binding sites in small fresh or frozen biopsies of rumen epithelium papillae. In
      bovine and ovine rumen epithelium obtained from the cranio-ventral rumen sac the
      concentration of [3H]ouabain binding sites was 1.6-4.9 nmol g dry wt-1 (n = 32)
      and 3.7-5.2 nmol g dry wt-1 (n = 6), respectively. When incubated in oxygenated
      Krebs-Ringer bicarbonate buffer fresh biopsies of rumen epithelium maintained a
      high K+ and low Na+ content for at least 6 h. Na+ loading of the biopsies induced
      about 20-fold increase of the Na+, K(+)-pump activity based on measurement of
      ouabain suppressible net [86Rb+] influx. The ouabain suppressible net influx of
      [86Rb+] measured in Na+ loaded biopsies showed a close correlation to the
      [3H]ouabain binding capacity (r = 0.80, P < 0.01) and corresponded to 47 +/- 2%
      (n = 9) of the theoretical maximum flux rate. The ouabain suppressible net influx
      of K+ and [86Rb+] were linearly related (r = 0.73; P < 0.001). The net Na+ efflux
      was 1.21 times the net K+ influx. It is concluded that rumen epithelium has a
      large capacity for active Na+/K+ transport and that there is agreement between
      the concentration of [3H]ouabain binding sites in the epithelium and the ouabain
      suppressible rate of net [86Rb+] influx in Na+ loaded biopsies in spite of some
      uncertainty about the maximum turnover number of the Na+, K(+)-pump in rumen
      epithelium.

PMID- 8553880
TI  - Fluid flow across the jejunal epithelia in vivo elicited by d-c current: effects
      of mesenteric nerve stimulation.
AB  - The aim of this study was twofold: (1) to investigate the effect of electrical
      gradients on fluid transport across the rat jejunal mucosa in vivo; and (2) to
      evaluate the effect of mesenteric nerve stimulation (MNS) on current-induced
      fluid flow. Segments of rat jejunum were mounted with intact blood circulation in
      an in vivo chamber, allowing parallel registration of net fluid transport rate
      (NFT) and electrical properties of the tissue. Directed currents (d-c) of varying
      densities were passed across the jejunal wall in both directions and the current
      induced fluid flows were measured. D-c current elicited fluid flows across the
      jejunal mucosa towards the cathode in both directions in a 'dose-dependent'
      manner. The effect was markedly greater when the anode was placed on the serosal
      side (s-->m current) than when it was placed on the mucosal side (m-s current).
      MNS abolished m-->s current induced flow whereas the effect of s-->m current was
      not significantly changed. It was concluded that: (1) true electro-osmosis
      probably accounts for the major portion of current-induced fluid flow in this
      model; (2) current induced fluid flow is rectified in opposite directions in vivo
      and in vitro; and (3) MNS inhibits current-induced fluid flow m-->s, possibly via
      a sympathetic effect on epithelial permeability.

PMID- 8553881
TI  - Facilitation of the human nociceptive reflex by stimulation of A beta-fibres in a
      secondary hyperalgesic area sustained by nociceptive input from the primary
      hyperalgesic area.
AB  - Hyperalgesia was induced in healthy volunteers by topical capsaicin applied on
      the dorsum of the foot within the receptive field of the sural nerve. Under
      presence of hyperalgesia different normally non-noxious conditioning stimuli were
      applied to the hyperalgesic area and the polysynaptic nociceptive spinal reflex
      and pain ratings were used to assess central excitability. The nociceptive reflex
      was measured in the knee extensor and flexor muscles evoked by electrical
      stimulation of the sural nerve trunk at an intensity of 1.5 times the initial
      reflex threshold (an intensity above the pain threshold). Thermal stimulation of
      the primary hyperalgesic area (re)established both on-going spontaneous pain and
      secondary hyperalgesia. Thus, increased nociceptive reflexes were recorded and
      increased pain intensity reported when A beta-fibres in the secondary
      hyperalgesic area were activated concurrently with the reflex testing after a non
      noxious thermal stimulation of the primary hyperalgesic area. The A beta-fibre
      activation was achieved by continuous low-intensity electrical stimulation (40
      Hz) that was initiated after on-going pain produced by the thermal stimulation
      had waned. The same measurement without prior thermal conditioning stimulation of
      the primary area resulted in no reflex facilitation, indicating rapid changes in
      the central excitability with existence of on-going nociceptive activity. This
      indicates that the development and maintenance of secondary hyperalgesia are
      dependent on sustained peripheral nociceptive activity. The study also shows that
      a central summation of nociceptive and non-nociceptive afferent activity can
      occur once secondary hyperalgesia is present.

PMID- 8553882
TI  - Effects of streptozotocin-induced diabetes, physical training and their
      combination on collagen biosynthesis in rat skeletal muscle.
AB  - The effects of streptozotocin-induced diabetes, physical training and their
      combination on the activities of prolyl 4-hydroxylase (PH) and
      galactosylhydroxylysyl glucosyl-transferase (GGT), both marker enzymes of
      collagen biosynthesis, and on the concentration of hydroxyproline (Hyp) were
      studied in vastus lateralis, rectus femoris and gastrocnemius muscles in rats.
      The experimental period was 12-16 weeks. Diabetes had an overall decreasing
      effect on specific PH activity in all muscles studied, whereas specific GGT
      activity remained at control level. Total PH and GGT activities decreased in all
      three muscles in the diabetic animals (P < 0.001). Training caused an increase in
      PH and GGT activities in gastrocnemius in non-diabetic rats, whereas training in
      combination with diabetes did not change specific PH or GGT activity. Diabetes
      increased specific Hyp concentration in vastus lateralis and gastrocnemius in
      trained diabetic rats (P < 0.05), whereas training decreased Hyp level
      significantly (P < 0.05) in vastus lateralis in non-diabetic rats, but not in
      diabetic animals. The results suggest that in streptozotocin-induced diabetes the
      decrease in collagen synthesis rate exceeds the negative total protein balance in
      the muscle. Although physical training may have an increasing effect on muscular
      collagen synthesis in non-diabetic rats, it is unable to prevent the decreasing
      effect of diabetes on collagen synthesis.

PMID- 8553883
TI  - Effect of furosemide on local and zonal glomerular filtration rate in the rat
      kidney.
AB  - Furosemide has been reported to produce disproportional changes in blood flow in
      cortical zones and to inhibit tubuloglomerular feedback (TGF), suggesting that
      furosemide might alter the intracortical distribution of glomerular filtrate. We
      have tested this hypothesis by a new method for measuring local and total
      glomerular filtration rate (GFR) based on proximal tubular accumulation of the
      basic polypeptide aprotinin (mol wt 6513). Local GFR was calculated in tissue
      samples dissected from outer cortex (OC), inner cortex (IC) and the
      corticomedullary border zone (CM) from the plasma clearances of two aprotinin
      tracers injected i.v. before and after a 3 min i.v. infusion of 25 mg kg-1
      furosemide. The mean of five samples from each region was used to determine zonal
      GFR. Isotonic saline was infused at a rate corresponding to urine flow.
      Furosemide reduced whole kidney GFR from 1.17 to 1.00 mL min-1 and gave a similar
      reduction of renal artery blood flow. Urine flow increased from 0.6 to 17% of
      GFR. Haematocrit (approximately 0.48) and plasma protein concentration
      (approximately 55 mg mL-1) were maintained while the arterial blood pressure
      tended to decline (118 +/- 5 mmHg to 108 +/- 6 mmHg, P < 0.05). GFR in OC, IC and
      CM (1.58, 1.18, 0.42 mL min-1 g-1) fell to 87, 88 and 88% of control after
      furosemide infusion respectively. The furosemide/control ratio for each sample
      showed a coefficient of variation of about 3%. We conclude that furosemide
      produced a modest GFR reduction that was uniform throughout the renal cortex. The
      homogenous GFR response suggests a similar TGF constriction tone in preglomerular
      vessels of deep and superficial nephrons.

PMID- 8553884
TI  - NMDA receptors in mouse barrel cortex during normal development and following
      vibrissectomy.
AB  - The development of N-methyl-D-aspartate (NMDA) receptors and the effects of
      vibrissectomy upon [3H]MK-801 binding were examined in the barrel cortex of mice.
      Autoradiographic studies showed that initially very low binding of [3H]MK-801
      sharply increased during the second postnatal week reaching the adult level by
      the end of the third week. Scatchard analysis performed on cortical membrane
      preparations indicated that this rise of [3H]MK-801 labelling was due to an
      increase in the number of binding sites and a decrease of Kd at postnatal day 15
      and 28. The interlaminar differences of labelling were registered from postnatal
      day 8. Changes of interlaminar distribution were found during the second and
      third postnatal weeks. In adult barrel cortex the highest binding was found in
      supragranular layers. In layer IV of the cortex, the pattern of binding resembled
      the pattern of barrels. Unilateral denervation of vibrissae performed in neonatal
      and adult mice did not alter the intensity of [3H]MK-801 labelling or the laminar
      distribution of binding sites. These results suggest that NMDA receptor binding
      does not reflect the plastic changes occurring in the barrel cortex.

PMID- 8553885
TI  - Calretinin immunoreactivity in adrenal glands of developing, adult and ageing
      Sprague-Dawley rats.
AB  - Localization of calretinin immunoreactivity in the rat adrenal gland was studied
      using immunohistochemical methods. Calretinin-immunoreactive adrenal chromaffin
      cells and nerve fibres were found at all of the ages examined from embryonic day
      16 up to 2-yr-old. Immunoreactive chromaffin cells showed a decrease in number
      with increasing age, and in the adult and ageing rats they were found among the
      adrenaline-storing chromaffin cells. Calretinin immunofluorescence was also
      observed in a few ganglion cells of the adult and ageing rats, and in most of the
      cortical cells at embryonic day 16. The density of immunoreactive nerve fibres in
      the gland showed a progressive increase with age to a peak by day 4 after birth
      and then a gradual decrease afterwards; they became associated mainly with some
      of the ganglion cells in the adult rat. As revealed by double labelling of
      calretinin immunoreactivity in adrenal sections from the adult rat with NADPH
      diaphorase histochemistry, no co-localization existed between calretinin and
      NADPH-diaphorase; however, a small number of neuronal cell bodies which contained
      nitric oxide synthase were found heavily surrounded with calretinin
      immunoreactive nerve fibres. In ageing rats, an increased density of calretinin
      immunoreactive nerve fibres was seen associated largely with the chromaffin
      cells. We conclude from this study that calretinin is found in the rat adrenal
      gland; the high degree of variability in its expression with age suggests that
      calretinin may be concerned with age-related activities in the gland.

PMID- 8553886
TI  - Astrocyte survival in the absence of exogenous substrate: comparison of immature
      and mature cells.
AB  - Astrocyte cultures prepared from newborn mouse neopallium were grown for either
      one or three weeks (representing, respectively, immature and mature astrocytes)
      and then exposed to deprivation of substrate (glucose and amino acids) for up to
      48 hr. Cultures which had been deprived of metabolic substrates for either 24,
      30, 36 or 48 hr were examined for lactate dehydrogenase efflux into the medium
      (an indicator of cell death) and ATP content. Significant cell death in mature
      astrocytes began after 30 hr of incubation in the substrate-deprived medium, a
      time when ATP had fallen to approximately 10% of its initial value. Immature
      astrocytes survived on a substrate-free medium for 48 hr before there was any
      indication at all of cell death, and this corresponded to a time when ATP values
      had fallen to 5% of the initial values. These findings are compared to previous
      observations during simulated ischemia (substrate deprivation plus anoxia) when
      (1) there was a faster cell death and (2) cell death occurred at higher ATP
      levels.

PMID- 8553887
TI  - Maturation of cerebellar granule cells is delayed in cultures derived from
      ethanol-treated chick embryos: survival and proliferation studies.
AB  - Previous studies from this laboratory have shown that ethanol administration to
      chick embryos during embryonic days 1-3, a critical period of neuroembryogenesis,
      differentially affects primordial CNS structures. In this study, chick embryos
      were treated in ovo with ethanol (10 mg/50 microliter/day) at E1 to E3. At 14
      days of embryonic age cerebellar (E14CE) granule cell cultures were prepared from
      both control and ethanol-treated embryos. Growth patterns were evaluated
      morphologically and the neuronal nature of these cultures was evaluated
      immunocytochemically. E14CE granule cell cultures exhibited neurofilament
      immunoreactivity demonstrating the neuronal-nature of these cultures. In addition
      E14CE granule cultures contained numerous glutamatergic neurons as assessed by
      positive glutamate immunoreactivity and also some GABAergic neurons as assessed
      by positive GABA immunoreactivity. Cultures derived from both control and ethanol
      treated embryos were labeled with 3H-thymidine and assessed for effects on
      survival and proliferation in culture. Cultures derived from ethanol-treated
      embryos showed a higher rate of proliferation and survival during the first 3
      days in culture as compared to those derived from controls. However, after 3 days
      in culture, survival was lower in the cultures from ethanol-treated embryos as
      compared to those derived from controls. We interpret these findings to mean that
      (a) ethanol arrested cerebellar granule cell development at an immature state;
      (b) immature neurons have a higher survival capacity than differentiated neurons;
      and (c) ethanol accelerates normal neuronal cell death as previously reported.

PMID- 8553888
TI  - Ethanol neurotoxicity on neuroblast-enriched cultures from three-day-old chick
      embryo is attenuated by the neuronotrophic action of GABA.
AB  - In the present study, using neuroblast-enriched cultures derived from three-day
      old chick embryos (E3WE), we examined the morphological effects of ethanol and/or
      GABA, as well as the developmental profile of the cholinergic and GABAergic
      neuronal phenotypes, as assessed by the activities of choline acetyltranferase
      (ChAT) and glutamate decarboxylase (GAD). Cultures exposed to ethanol (50 mM)
      exhibited smaller and fewer aggregates than controls with a neuritic network that
      lacked fasciculation. In cultures treated with GABA (10(-5) M) alone or
      ethanol+GABA the size and number of the neuronal aggregates was increased and
      also neuritic arborization and fasciculation was enhanced. Thus, addition of GABA
      restored the normal growth pattern in the ethanol-treated cultures. As previously
      shown, E3WE culture treated with ethanol alone showed a decrease in both ChAT and
      GAD activities compared to controls. Both cholinergic and GABAergic neuronal
      phenotypes were enhanced in cultures treated with GABA as assessed by increases
      in ChAT and GAD activities, respectively, compared to controls. Moreover, in
      cultures treated concomitantly with ethanol and GABA both ChAT and GAD activities
      were higher than in ethanol-alone-treated cultures. Thus, the presence of GABA in
      the ethanol-treated cultures counteracted the decline in ChAT and GAD activities
      observed in the ethanol-alone-treated cultures. We conclude that GABA through its
      neuronotrophic actions can rescue neuroblasts from ethanol insult and restore
      neuronal phenotypes.

PMID- 8553889
TI  - Effects of adenosine on cAMP production during early development in the optic
      tectum of chicks.
AB  - Accumulation of cyclic adenosine monophosphate (cAMP) elicited by adenosine was
      studied in slices and membrane preparations of optic tectum from chicks aged 1-13
      days post-hatch. Accumulation of cAMP promoted by adenosine declined with age,
      the highest value being observed in three-day-old chicks and the lowest in 11-day
      old chicks. However, when the slices were incubated with adenosine and the
      phosphodiesterase inhibitor-Ro 20-1724 the differences between the two ages were
      abolished, suggesting a higher phosphodiesterase activity in 11-day-old chicks.
      In membrane preparations, although basal adenylate cyclase activity was lower in
      three-day-old chicks, the guanylyl-imidodiphosphate (Gpp(NH)p) concentration
      curves for stimulation of adenylate cyclase activity indicated a higher
      sensitivity of G protein to Gpp(NH)p at this age. This hypothesis was reinforced
      by the observation that the binding of [3H]Gpp(NH)p to the membrane preparation
      was greater in three-day-old animals. In spite of these differences, the
      percentage of adenylate cyclase activity stimulation by 2-chloroadenosine
      (2CADO)+Gpp(NH)p was the same at both ages. These findings suggest that the
      decreased response evoked by adenosine during development is probably due to
      increased phosphodiesterase activity and a lower sensitivity of adenylate cyclase
      activity to Gpp(NH)p.

PMID- 8553890
TI  - Glial-like cells of the rat pituitary intermediate lobe change morphology and
      shift from vimentin to GFAP expression during development.
AB  - This study demonstrated morphological changes in glial-like cells of the rat
      pituitary intermediate lobe during early postnatal development, and a subsequent
      shift in protein expression from vimentin to GFAP. Vimentin immunoreactivity was
      detected in the lobe at embryo day 14 and was localized in radially-oriented,
      bipolar cells whose processes spanned the thickness of the intermediate lobe. At
      electron microscopical resolution, processes contained intermediate filaments,
      cell nuclei were indented while secretory vesicles characteristic of the
      endocrine cells were not found. Vimentin immunoreactive intensity began to
      decrease at postnatal day 5. By postnatal day 7, vimentin-positive, stellate
      cells were observed, with few radial processes found by day 10. The intensity of
      vimentin immunoreactivity decreased through day 25. Within the lobe parenchyma,
      vimentin was localized in glial-like cells since double-label
      immunohistochemistry revealed no colocalization of beta-endorphin and vimentin,
      or fibronectin and vimentin. Dopamine-containing axons were in close apposition
      to vimentin-positive processes. GFAP immunoreactivity first appeared on postnatal
      day 20 and, by day 25, stellate cell bodies with three to six extended processes
      were evident. Cells were primarily distributed in the caudal third of the lobe.
      The characteristic adult pattern of cell clusters in latero-dorsal and ventral
      portions of the lobe was fully established by postnatal day 55. The transition
      from vimentin to GFAP expression and concurrent morphological changes resemble
      those described for radial glial during cerebral cortical development.

PMID- 8553891
TI  - Transient expression of S-100 by melanotropes of the rat pituitary intermediate
      lobe during development.
AB  - S-100, an acidic calcium-binding protein, is co-localized with vimentin in glial
      like cells in the adult rat pituitary intermediate lobe. S-100 and melanotrope
      markers were not co-localized in the adult. During development, S-100 and
      vimentin were not co-localized but appeared in cells with different morphological
      characteristics. S-100 was co-localized with POMC mRNA and beta-endorphin during
      prenatal time and the first three postnatal weeks. This was demonstrated by
      double-label immunohistochemistry, using combinations of antisera against S-100,
      vimentin and beta-endorphin, and in situ hybridization histochemistry for POMC
      mRNA combined with immunohistochemistry for S-100. In the second and third weeks
      of postnatal development, S-100 was observed in fewer melanotropes and more
      frequently in stellate cells, which also expressed vimentin. Thus, S-100 appeared
      to be transiently expressed in melanotropes during prenatal and early postnatal
      development. S-100 serves as a neurotrophic and glial maturation factor in the
      CNS. Since S-100 expression in melanotropes coincides with the onset of
      dopaminergic innervation and morphological changes in glial-like cells of the
      lobe, it could have similar functions in the rat pituitary intermediate lobe.

PMID- 8553892
TI  - Effects of nerve growth factor on sympathetic neuron development in normal and
      limbless chick embryos.
AB  - Wing bud removal in chick embryos has been shown to affect the generation of
      sympathetic neurons prior to the normal period of limb innervation [Saltis and
      Rush (1995) J. auton. nerv. Sys., 51, 117-127.]. Pyknotic activity occurred
      earlier within the peripherally deprived ganglion, suggesting that a precocious
      cell death of dividing sympathoblasts led to the reduced neuronal population. We
      have now sought to test whether the effect of limb bud extirpation can be
      overcome by the administration of nerve growth factor (NGF). Specifically, the
      peripherally deprived ganglion has been examined for mitotic activity and total
      neuronal numbers. In brachial ganglia from the operated side, neuron numbers
      decreased by 67% by embryonic day (E) 13, but by only 28% when NGF was
      administered from E9. Ganglia on the unoperated side were unaffected by the NGF
      treatment. In contrast, in embryos receiving NGF from E5 to E9, neuron numbers in
      the ganglia increased by more than 100%, on both the intact and operated side.
      This increase was accompanied by a greater proportion of 3H-thymidine-labelled
      neurons. We therefore conclude that NGF, in addition to its previously described
      role of preventing naturally occurring neuron death, can also affect the
      generation of sympathetic neurons. This ability of NGF to affect gangliogenesis
      is most likely achieved by increasing the survival of dividing neuroblasts,
      although a direct effect on mitosis has not been excluded.

PMID- 8553893
TI  - Utrophin expression during human fetal development.
AB  - Utrophin, a protein encoded by chromosome 6 is highly homologous to the cysteine
      rich domain and most of the C-terminal domain of dystrophin. In order to clarify
      its functional role we analyzed its expression during human fetal development. We
      carried out immunohistochemical analysis on muscle from normal human fetuses at
      different ages of gestation using an antibody directed against a specific COOH
      terminal sequence of the protein. In addition, we stained serial sections with
      antibodies against dystrophin and alpha-bungarotoxin FITC-BTX. Our findings show
      that, at week 9 of gestation, utrophin is diffusely expressed in the cytoplasm.
      From week 12 to 22 the immunostaining is still cytoplasmic, though the reaction
      intensity progressively decreases. Moreover we observed a strong reaction in
      fetal nerve at week 18 and 22. There was no correlation between utrophin
      expression and progressive dystrophin membrane localization.

PMID- 8553894
TI  - Cocultures of meningeal and astrocytic cells--a model for the formation of the
      glial-limiting membrane.
AB  - The glial-limiting membrane at the border of the central nervous system (CNS)
      consists of glial endfeet covered by a basal lamina. The formation of the glia
      limitans seems to be controlled by adjacent meninges but only little is known
      about this interaction. In the present study astrocytes and meningeal cells were
      investigated in vitro to see if cocultures of these cells can serve as a suitable
      model for the differentiation of the glial-limiting membrane and can be used to
      define the conditions under which the glial-limiting membrane develops. The
      following observations were made in cocultures of meningeal and astrocytic cells
      of two-day-old rats: (i) epithelioid astrocytes were transformed into stellate
      cells; (ii) single colonies of proliferating epithelioid astrocytes were
      generated; (iii) the area around these colonies becomes devoid of meningeal
      cells, which seem to form a circular border around the astroglial islands; (iv)
      from the glial colonies long thin glial processes grow towards the surrounding
      meningeal cells, terminating at the site of contact; (v) in the contact zone
      between meningeal cells and astrocytes irregular shaped deposits of electron
      dense material resembling a basal lamina were seen. These observations indicate
      that indeed a structure resembling a glial-limiting membrane develops in
      cocultures of meningeal and astrocytic cells. Its formation depends on the
      balance of growth promoting effects of meningeal cells on astrocytes and growth
      inhibiting effects of astrocytes on meningeal cells. Both activities can be
      enriched from conditioned media of pure astrocytic or meningeal cell culture. The
      proposed model of meningo-astrocytic cocultures may be a helpful instrument for
      further investigations on the formation of the glia limitans.

PMID- 8553895
TI  - Developmental expression of tau proteins in the chicken and rat brain: rapid down
      regulation of a paired helical filament epitope in the rat cerebral cortex
      coincides with the transition from immature to adult tau isoforms.
AB  - The monoclonal antibodies TAU-1 and AT8 are directed at human microtubule
      associated protein tau epitopes that contain a dephosphorylated and
      phosphorylated Ser202, respectively, while AT180 and AT270 are anti-tau
      monoclonals with epitopes that require phosphorylated Thr181 and Thr231,
      respectively. We used these antibodies to study the developmental profiles of tau
      proteins in rat cerebral cortex and chicken optic lobes. In tau extracts from
      perinatal rat cerebral cortex. AT8 recognized one major protein band of
      approximately 50 kDa that peaks on postnatal day 6 and declines rapidly to lower
      levels at day 12. At later stages, the AT8 epitope was expressed by several adult
      tau isoforms that were, however, stained only very faintly in highly enriched
      samples. Two additional tau epitopes recognized by AT180 and AT270 were found to
      be expressed by one or two protein bands up to about postnatal day 19 and then
      declined. Unlike the AT8 epitope, in the mature brain these epitopes were stained
      strongly in enriched samples, where they were expressed by a greater number of
      adult isoforms. Between embryonic day 19 and postnatal day 12, TAU-1 was found to
      recognize one major protein band of approximately 50 kDa which migrated slightly
      faster than the AT8-binding band. At postnatal day 19 and all older stages
      (including adult cortex), at least three additional TAU-1-binding isoforms with
      higher apparent molecular weights were present. Hence, the transition from one
      immature to several adult TAU-1-binding tau isoforms between postnatal day 12 and
      19 in rat cerebral cortex coincides with the phase of rapid down-regulation of
      the AT8 epitope. As in the rat cerebrum, in chicken optic lobes there is a
      developmental decrease of AT8-binding proteins which is paralleled by striking
      changes in the electrophoretic pattern of tau isoforms recognized by TAU-1. In
      both rat cerebral cortex and chicken optic lobes, the period of maximal
      expression of AT8-binding tau is morphologically characterized by intense axonal
      growth and beginning synaptogenesis, whereas its subsequent rapid down-regulation
      and the appearance of novel TAU-1-binding isoforms correlates with synaptic
      maturation, the onset of spontaneous electrical activity and the beginning of
      myelination.

PMID- 8553896
TI  - Brain large neutral amino acids and catecholamines in parenterally nourished
      preterm rabbits.
AB  - Total parenteral nutrition (TPN) has been adapted as a standard for providing
      nutrition to ill term and preterm infants. The availability of tyrosine in amino
      acid preparations utilized for TPN is limited and may potentiate a tyrosine
      deficient state. Phenlyalanine hydroxylase activity, responsible for catalyzing
      tyrosine synthesis, has been suggested to be decreased in fetal and neonatal
      animals. Parenterally nourished premature rabbits (n = 16) and suckled rabbits (n
      = 19) were studied in order to compare growth parameters and amino acids in the
      plasma and brain, as well as whole brain catecholamine concentrations. Influx
      velocities into the brain of amino acids were also determined in these two
      groups. The preterm rabbit's average birth weight (42.6 +/- 6.0) was less than
      that of term rabbits (56.7 +/- 8.7, P < 0.005). Significantly lower
      concentrations of the catecholamine precursor tyrosine were found in both the
      plasma and brain of the parenterally nourished animals compared to the suckled
      animals. Tyrosine is reduced in the brain in TPN-supported animals reflecting
      both low tyrosine intake and increased plasma concentrations of large neutral
      amino acids that compete for uptake at the blood-brain barrier. However, no
      difference was observed between the two groups in their brain catecholamine
      concentrations. The seven-day parenterally nourished rabbit appears to be
      tyrosine-deficient but no evident effects on brain catecholamine concentrations
      were seen. The effects and impact of a tyrosine-deficient state might better be
      evaluated by regional evaluation of catecholaminergic areas of the brain or over
      a longer period of parenteral nutrition.

PMID- 8553897
TI  - Reinnervation of denervated iris by transplanted sympathetic ganglia: effect of
      neuronal age.
AB  - Neuronal outgrowth in vivo is aggressive postnatally, but is diminished with
      increasing age. This may be attributable to intrinsic features of the neuron or
      its interaction with other components of the developing organism. The purpose of
      this study was to determine if there is an age-dependent reduction in the
      intrinsic ability of sympathetic neurons to initiate fiber outgrowth. Superior
      cervical ganglia from donor rats aged 3-4, 11-12, 27-28 and 45-46 days were
      removed and transplanted to the anterior chamber of the sympathectomized eye of
      host rats 85-89 days of age. Ganglia with host irides were removed at 3, 6 and 10
      days post-transplant and whole mounts were analysed using catecholamine
      histofluorescence for maximum sympathetic fiber density, length and initial rate
      of outgrowth. Fluorescent fibers were present in host irides of donors of all
      ages and at all post-transplant times. However, maximum fiber density was less
      for the 3-4-day-old donor ganglia (e.g. 43-71% of 11-46-day-old donor ganglia at
      600 microns, 10 days post-transplant). Maximum fiber length was also less in the
      youngest group (e.g. 35-49% of 11-46-day-old donor ganglia, 10 days post
      transplant). Further, the initial rate of outgrowth was decreased for the 3-4-day
      old donor ganglia (128 +/- 46 microns/day for the 3-4-day-old ganglia vs 253 +/-
      48 microns/day for the 11-12-day-old ganglia, 307 +/- 35 microns/day for the 27
      28-day-old ganglia and 260 +/- 22 microns/day for the 45-46-day-old
      ganglia).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8553898
TI  - DNA neosynthesis in Auerbach plexus ganglia isolated from the rat hypertrophic
      gut: an electrophoretic analysis.
AB  - We analysed using electrophoresis the total genomic DNA extracted from isolated
      Auerbach plexus ganglia of the hypertrophic duodenum upstream from a partial
      experimental stenosis. Results indicated the presence of two extra-bands
      migrating below the high molecular weight DNA. suggesting that DNA amplification
      is the basic mechanism of the DNA neosynthesis previously observed in myenteric
      neurons.

PMID- 8553899
TI  - Exposure to lead-acetate modulates the developmental expression of myelin genes
      in the rat frontal lobe.
AB  - Postnatal exposure to high levels (4%) of lead (Pb) have been shown to disrupt
      myelin formation and result in abnormal conduction of nerve impulses, components
      necessary for information processing in the CNS. To investigate whether the
      pathological changes in myelin, due to Pb exposure, might be partially mediated
      by modulations of the expression of genes involved in CNS myelin, we have
      examined the developmental profiles of the proteolipid protein (PLP) and myelin
      basic protein (MBP), two major structural constituents of CNS myelin and 2',3'
      cyclic nucleotide 3' phosphodiesterase (CNP), a non-structural enzyme associated
      with myelin formation. Rat pups were postnatally exposed, from birth to weaning,
      to moderate amounts of Pb (0.2%), in the drinking water of the dam, and their
      frontal cortices were assayed for changes in the expression profile of the above
      genes by Northern Analysis. On PND 20, Pb resulted in a dramatic stimulation of
      the mRNA levels of PLP and a small increase in MBP mRNA levels, but had no effect
      on the CNP message. These data suggest that moderate levels of Pb selectively
      interfere with the gene expression of structural proteins of CNS myelin and may
      thus influence the composition of myelin in this way.

PMID- 8553900
TI  - Effect of a spinal cord photolesion injury on catalase.
AB  - Ischemic injury to the spinal cord results in cell and tissue damage. Oxygen free
      radicals have been implicated in post-ischemic cell injury and death while free
      radical scavengers like superoxide dismutase and catalase are associated with an
      amelioration of ischemic injury. Measurement of catalase enzyme activity or
      protein in ischemic tissue presents mechanical problems due to extensive tissue
      destruction. Therefore, we looked at the effects of a photochemical lesion (which
      reproduces ischemic injury) on the levels of catalase mRNA in the spinal cord
      tissues of rodents under various experimental conditions. A significant depletion
      in the levels of catalase mRNA was observed in the spinal cord tissues of rats
      that received a severe lesion and were sacrificed 6 days post-lesion, while
      levels of catalase mRNA in the spinal cord tissues of similarly lesioned rats
      sacrificed 14 days post-lesion showed a return to control values.

PMID- 8553901
TI  - Effect of early cortical lesion on the acute model of epilepsy.
AB  - The experiments were performed in order to investigate the sparing of function
      following early postnatal cortical lesion in the acute rat model of epilepsy.
      Sensorimotor cortex was unilaterally removed at 9 and 10 days of postnatal age in
      lesioned animals, while control animals were only sham operated (at the same
      early stage of life) or non-operated (before implantation of the electrodes).
      Seizure activity was recorded by means of electroencephalograms at adult stage of
      life induced by parenteral administration of penicillin (1,000,000 I.U./kg,
      i.p.). Our results showed that when the cortical lesion was performed in infancy
      (on the contrary to the lesion performed in adulthood) there was no prolongation
      of seizure activity in an acute model of epilepsy.

PMID- 8553902
TI  - Regulation of IgE synthesis in humans.
AB  - At the present time, in no other system are the signals required for isotype
      switching better understood than in the IgE system. IgE switching is therefore
      becoming a general model for "directed" isotype switching in mice and humans. The
      study of IgE regulation has proposed a paradigm of general importance for
      immunology in the nineties, namely, the requirement for at least two signals in
      order to trigger the final event, in this case DNA switch recombination to the
      IgE isotype. The first signal is delivered by a cytokine, IL-4 or IL-13, and is
      responsible for the choice of the isotype. The second signal is typically
      delivered upon engagement of CD40 on B cells by the CD40 ligand expressed on T
      cells, and results in switching and production of IgE. We shall herein discuss
      the two-signal model for IgE switching in detail, stressing in particular the
      cross-talk between signals, and the mechanisms responsible for IgE amplification.

PMID- 8553903
TI  - Orally administered interferon-gamma but not tumor necrosis factor-alpha suppress
      infection with Salmonella typhimurium in a mouse model.
AB  - Intragastrically inoculated Salmonella typhimurium produces a systemic infection
      in mice with high mortality. We have examined the effect of interferon (IFN)
      gamma and tumor necrosis factor (TNF)-alpha on the development of the disease.
      IFN-gamma reduced penetration of bacteria into the gut epithelial cells, reduced
      the development of bacteremia, reduced mortality and prolonged the length of
      survival of mice both after peroral and after intraperitoneal administration. On
      the other hand TNF-alpha had a similar effect only when given intraperitoneally
      but not by peroral route. These findings indicate that the mechanisms by which
      these two cytokines influence the development of S. typhimurium infection are
      different. This is the first observation that perorally administered cytokines
      may have local and systemic effects on bacterial infection.

PMID- 8553904
TI  - Correlation between pretreatment serum levels of neopterin and response to
      interleukin-2 immunotherapy in cancer patients.
AB  - IL-6 levels have been proven to correlate with resistance to IL-2 immunotherapy.
      Since IL-6 may be produced by both macrophages and TH2 lymphocytes, it is not
      possible to establish whether the negative prognostic significance of IL-6 levels
      may primarily depend on an enhanced macrophage or TH2 activation. Macrophage
      activation may be documented by the increase in its specific marker neopterin. In
      an attempt to establish whether the negative significance of IL-6 high levels
      prior to IL-2 immunotherapy may reflect an enhanced macrophage activation, we
      have investigated the relation existing between pretreatment concentrations of
      neopterin and response to IL-2 immunotherapy in cancer patients. The study
      included 20 metastatic renal cell cancer patients, who were treated with IL-2
      subcutaneously at 6 million IU/day for 5 days/week for 6 weeks. Before the onset
      of IL-2 therapy, abnormally high serum levels of neopterin were seen in 11/20
      patients. Moreover, neopterin concentrations were significantly correlated with
      those of IL-6. Tumor regression rate was significantly higher in patients with
      normal than in those with elevated levels of neopterin prior to therapy (5/9 vs
      1/11, P < 0.05), as well as the percent of the survival at 1 year (9/9 vs 4/11, P
      < 0.01). This preliminary study would suggest that pretreatment values of the
      macrophage marker neopterin correlate with resistance to IL-2 cancer
      immunotherapy.

PMID- 8553905
TI  - Cellular and molecular analyses of interferon beta cytopathic effect on HPV-16 in
      vitro transformed human keratinocytes (HPK-IA).
AB  - Recently, Interferon (IFN) beta has been reported to induce on HPK-IA cell line,
      an unusually marked cytopathic effect. Surprisingly this effect is not shared
      with IFN alpha. The morphological aspect of this cytopathic effect recals the one
      induced by highly cytopathic viruses. It has an induction time of less then four
      hours, may be inhibited by protein synthesis inhibitors and has a characteristic
      protein SDS-PAGE pattern. RT-PCR analysis has shown that IFN beta, but not alpha
      or gamma, reduces the transcription level of E6/E7 viral mRNA. Taken together
      these data suggest that cells may finely discriminate between IFN alpha and beta.
      Regarding HPK-IA cells this discrimination allows the activation of a specific
      transduction pathway ultimately leading to cell death. Cell death may be due to
      the concomitant severe reduction of E6/E7 viral transcription observed.

PMID- 8553906
TI  - Immune effects of preoperative immunotherapy with high-dose subcutaneous
      interleukin-2 versus neuroimmunotherapy with low-dose interleukin-2 plus the
      neurohormone melatonin in gastrointestinal tract tumor patients.
AB  - Surgery-induced immunosuppression could influence tumor/host interactions in
      surgically treated cancer patients. Previous studies have shown that high-dose IL
      2 preoperative therapy may neutralize surgery-induced lymphocytopenia. Moreover,
      experimental studies have demonstrated that the immunomodulating neurohormone
      melatonin (MLT) may amplify IL-2 activity and reduce its dose required to
      activate the immune system. On this basis, we have compared the immune effects of
      presurgical therapy with high-dose IL-2 with respect to those obtained with
      preoperative neuroimmunotherapy consisting of low-dose IL-2 plus MLT. The study
      included 30 patients with gastrointestinal tract tumors, who were randomized to
      undergo surgery alone, or surgery plus a preoperative biotherapy with high-dose
      IL-2 (18 million IU/day subcutaneously for 3 days) or low-dose IL-2 (6 million
      IU/day subcutaneously for 5 days) plus MLT (40 mg/day orally). Patients underwent
      surgery within 36 hours from IL-2 interruption. Both IL-2 plus MLT were able to
      prevent surgery-induced lymphocytopenia. However, mean number of lymphocytes, T
      lymphocytes and T helper lymphocytes observed on day 1 of postoperative period
      was significantly higher in patients treated with IL-2 plus MLT than in those
      receiving IL-2 alone. Moreover, toxicity was less in patients treated with IL-2
      and MLT. This biological study shows that both immunotherapy with high-dose IL-2
      or neuroimmunotherapy with low-dose IL-2 plus MLT preoperatively are tolerated
      biotherapies, capable of neutralizing surgery-induced lymphocytopenia in cancer
      patients. Moreover, the study would suggest that the neuroimmunotherapy may
      induce a more rapid effect on postoperative immune changes with respect to IL-2
      alone.

PMID- 8553907
TI  - Staurosporine inhibits interferon alpha-induced gene expression in Friend
      erythroleukemia cells through a PKC independent pathway.
AB  - Interferons (IFNs) are able to induce an increased transcription of several
      genes, which can occur within minutes of the binding of IFNs to their receptors.
      The specific induced transcription is mediated by the interaction of specific
      transcription factors with regulatory DNA sequences that lie upstream the
      promoters of IFN induced genes. Phosphorylation of IFN-specific transcription
      factors is required for activation of transcription. We have studied the
      antiviral effect and the induction of gene expression by IFN-alpha in Friend
      Leukemia cells (FLC) in the presence of a series of inhibitors of known kinases.
      Protein kinase C (PKC)-specific inhibitors, i.e. calphostin C and
      bisindolylmaleimide, failed to influence the IFN-induced gene expression and the
      antiviral state. Likewise, little or no effect was found using inhibitors such as
      H7 or K252a. Chronic exposure of FLC to phorbol ester, that causes down
      regulation of PKC (the effectiveness of TPA treatment was proven by PKC enzymatic
      assay), has no effect on IFN-alpha action. In addition, treatment of FLC with
      staurosporine prevented the induction of IFN-stimulated genes and the
      establishment of the antiviral state only when this drug was used at high dosage
      (500 nM). This result indicates that, also in FLC, activation of PKC is not
      involved in the transcriptional response of the cells to IFN-alpha treatment. The
      non receptor tyrosine kinases of the JAK family that take part in the IFNs
      specific transduction pathways could be the target of the staurosporine specific
      inhibition of the IFN-alpha action.

PMID- 8553908
TI  - "Tubulofilamentous particles" are not scrapie-specific and are unrelated to
      tubulovesicular structures.
AB  - "Tubulofilamentous particles" has been defined as "thick" tubules, apparently
      distinguishable from other cytoskeletal elements, in touch-preparations from
      scrapie- and Creutzfeldt-Jakob disease (CJD)-infected brains. I report here that
      "tubulofilamentous particles" are nonspecific findings unrelated to
      "tubulovesicular structures" (TVS) which are the only particles consistently
      observed in brains of naturally occurring and experimentally induced SSVE.

PMID- 8553909
TI  - The role of raphe and tractus solitarius neuronal structures in the modulation of
      respiratory pattern in rabbits.
AB  - We studied the effects of MNR stimulation on phrenic (Phr) electroneurogram and
      external intercostal muscles (EI) electromiogram in spontaneously breathing
      rabbits. Additionally, experiments were performed before and after lignocaine
      blockade of nucleus tractus solitarii (NTS) to determine whether the information
      from MNR is transmitted via NTS neurones. The completeness of the blockade of NTS
      region was checked by studying the Hering-Breuer reflex. MNR was stimulated at
      the level 2-7 mm rostral to the obex. Stimulation at the rostral part of this
      region produced inhibition of phasic inspiratory activity, whereas stimulation in
      the caudal part elicited tonic activity throughout the respiratory cycle. These
      effects were more pronounced on EI than Phr. Responses to MNR stimulation were
      attenuated after lignocaine blockade, suggesting that the neurons located in NTS
      take part in the transmission of the modulatory information from the MNR to
      respiratory motoneurones.

PMID- 8553910
TI  - Projections from the visual areas to the neostriatum in rats. A re-examination.
AB  - Neostriatal afferents from the primary visual cortex in rats were studied using
      dextran-biotin, biocytin, and Fluoro-Gold. The area V1 was found to project only
      to a dorsomedial, longitudinal region of neostriatum (NS), bordering on the
      lateral ventricle and subcortical white matter. The preterminal fibres in the NS
      form fluffs which increase in number and density in the cases with larger
      injections. This target region is poorly stained for calbindin and yet belongs to
      the matrix compartment. The secondary visual areas also project to the
      dorsomedial NS region but they also innervate the deeper tissue in the same
      general region. Iontophoresis of Fluoro-Gold into the dorsomedial NS labelled
      some pyramidal neurones in the fifth layer of the primary visual cortex. The
      cortical areas that surround the visual cortical complex project to other regions
      of the NS: the somatosensory cortex to a dorsolateral longitudinal region and the
      auditory area to the medial half of the caudalmost portion of NS. Thus, major
      sensory cortical divisions project to non-overlapping NS regions. Since NS in
      monkeys and cats does not receive afferents from the primary visual cortex and in
      a number of other species does, we conclude that visual systems in different
      mammals differ with respect to their projections to NS.

PMID- 8553911
TI  - Variability analysis of visual evoked potentials in humans by pattern recognition
      in phase domain.
AB  - A novel approach to single trial visually evoked potentials (VEP) variability
      analysis based on a new model of post-stimulus brain electrical activity is
      presented. The convolution model introduced by the author is experimentally
      verified by the analysis of flash stimulus effects on EEG amplitude and phase
      spectra. Pattern recognition in the signal phase domain is proposed for detection
      of any time locked transient signals. This is illustrated by an application of a
      clustering algorithm in two-dimensional unwrapped phase of EEG Fourier transform
      space for occipitally recorded VEPs in human subjects.

PMID- 8553912
TI  - Topography of primary afferent projections in the trigeminal sensory nuclei of
      rats.
AB  - The afferent projection pattern from individual vibrissae follicles was related
      to the distribution of cytochrome oxidase (CO) dark cell clusters in the
      trigeminal sensory nuclei of adult rats to determine whether segregated primary
      afferent projections limit the extent of the topographic reorganizations that can
      occur at the level of the brainstem on a short term basis after changes in
      sensory driven activity. The results indicate that the projections to all the
      brain stem trigeminal subnuclei, including the principal sensory nucleus and the
      three subdivisions of the spinal trigeminal nucleus, are topographic; however,
      the extent to which label from different whisker rows overlap appears to differ
      from subdivision to subdivision. In the principal sensory nucleus there is nearly
      a one to one relationship between the inputs from the vibrissae follicles and the
      corresponding CO-dense clusters. Thus, little overlap of inputs from different
      vibrissae rows is likely. In contrast, in the pars interpolaris and, to a lesser
      extent, in the pars caudalis, inputs from individual vibrissae follicles extend
      beyond the appropriate CO-dark patch into adjacent whisker patches; thus, inputs
      to these subdivisions from different vibrissae likely overlap more extensively.

PMID- 8553913
TI  - Bilateral lesions of the pedunculopontine tegmental nucleus affect feeding
      induced by electrical stimulation of the ventral tegmental area.
AB  - The pedunculopontine tegmental nucleus (PPN) is anatomically connected with
      dopaminergic cells in the ventral mesencephalon, which are known to participate
      in the regulation of various adaptive appetitive behaviours. In the present
      experiment we studied a possible involvement of PPN in feeding elicited by
      stimulation of the ventral tegmental area (VTA). It was found that bilateral
      electrolytic lesioning of the PPN affected VTA-elicited feeding. However, the
      effects were diverse and showed dependence on the localization of the lesion
      within the PPN area. Lesions localized anteriorly in the PPN impaired VTA feeding
      whereas those involving the middle portion of the nucleus facilitated
      electrically elicited food ingestion. A precise alignment of the lesion and the
      area activated at the site of stimulation appeared crucial for the effect of the
      lesion. The results indicate that PPN belongs to the central feeding circuitry
      and it contains both activating and inhibiting elements directed to the ventral
      tegmental area.

PMID- 8553914
TI  - The effect of vasopressin analogue [d(CH2)5(1),Tyr(Me)2]AVP on memory process in
      rats with experimental amnesia.
AB  - We investigated the effect of a single 2 micrograms dose of vasopressin (AVP)
      analogue [(CH2)5(1),Tyr(Me)2]AVP on the processes of retrieval of conditioned
      reflexes in rats with experimentally induced amnesia. The models used were:
      electroconvulsive shock (ECS) and hypoxia. It severely impaired the memory
      processes. The AVP analogue [d(CH2)5(1),Tyr(Me)2]AVP facilitated retrieval of
      passive avoidance in all animals.

PMID- 8553915
TI  - Investigation of coherence structure and EEG activity propagation during sleep.
AB  - Overnight sleep EEG recorded from 21 derivations was studied for 7 subjects (4
      normal and 3 depressive). The multichannel autoregressive model was fitted to all
      21 channels simultaneously. Ordinary, multiple and partial coherencies and
      directed transfer function were estimated for sleep stages and wakefulness.
      Ordinary coherencies give rather trivial information that coherence decreases
      with the distance. Partial coherencies revealed specific structure to a large
      degree repeatable for studied subjects. Study of directed transfer function made
      possible the identification of main centres from which EEG activity is spreading
      during sleep. An EEG analysis, based on treating signals as a realization of one
      process and on simultaneous (not pair-wise) evaluation of time series, offers new
      possibilities in the investigation of synchronization and functional relations in
      brains.

PMID- 8553916
TI  - Neurotoxic effect of sodium tellurite in the rat temporal lobe.

PMID- 8553917
TI  - Effect of early illumination conditions on illumination preferences in the ant.

PMID- 8553918
TI  - [Hubertus Tellenbach: psychiatrist and humanist (1914-1994)].

PMID- 8553919
TI  - [Epilepsy and delinquent behavior].
AB  - Many authors through medical history have established that epilepsy and violent
      behavior are related. Although not corroborated in all the studies focussing on
      this matter, prevalence data show an increase number or epilepsy patients between
      prisoners, and is also found altered electroencephalograms in some violent
      people. A relation between a specific type of epilepsy and these behavior it has
      not been discovered. This connection between epilepsy and antisocial behavior
      have been studied in the ictal and interictal period and explained through
      different ways. Specific criteria have been described by some authors, trying to
      evaluate if the fit and the crime are closely related, but no characteristic type
      of crime is related with epileptic patients. We have made a review of the
      literature on this topic, considering the legal aspects and with reference to
      various countries justice resolutions.

PMID- 8553920
TI  - [Stress and adjustment at the beginning of postgraduate medical training].
AB  - The beginning of the Postgraduate Medical Training is a very stressful period.
      Young Doctors begin to confront with the difficulties and responsability of the
      medical practice. Simultaneously they face important innovations, due to changes
      in their life style. This work was transversally designed and performed in 250
      young doctors in the beginning of their postgraduate training. The association
      between psychopathological disturbances, psychosocial vulnerability factors and
      coping behaviour was evaluated. An elevated stress level was observed and the
      prevalence of psychiatric disorders was 31%. A discriminant analysis was
      performed and the presence of psychopathology was strongly associated with the
      coping behaviour and in a minor degree the personality profile. In the same
      analysis neither sociodemographic data and nor the stress level demonstrated any
      relation to the psychopathology symptoms. These findings emphasize that
      principally the coping behaviour, and also the personality profile plays an
      important role in the adaptation to this difficult period.

PMID- 8553921
TI  - [The study of suicides and homicides in Spain. Years 1980-1990].
AB  - A descriptive epidemiological was carried out in order to evaluate true scope of
      the problem of suicides and homicides in Spain. These two items were considered
      individually. With regard to the cases of suicides and homicides published in
      Causes of Death Spain, the mortality rates, tendency and potential years of life
      lost (PYLL) were calculated. We have found that the suicides rates are higher
      than the homicide and both are higher in men than in women. The provinces having
      the highest suicide rates are: La Rioja, Ceuta and Melilla, Asturias and Galicia.
      Those have the lowest Castilla-Leon. By means of the tendency study, we have
      noted a greater increase in Barcelona, Madrid and Valencia for the period 1980
      90. Regarding homicides, the only provinces showing statistically significative
      values are Jaen, Las Palmas and Guipuzcoa. The provinces with highest rates of
      PYLL, in men, were Galicia, Asturias and Navarra; were observed in the women of
      Cantabria and Madrid in the case of suicides, and Castilla-La Mancha, Asturias,
      Ceuta and Melilla in case of homicides.

PMID- 8553922
TI  - [The psychiatric consultation-liaison program and posttraumatic stress disorder
      due to burns].
AB  - Sixty-five acute burned inpatients were evaluated prospectively by structured
      questionnaire and clinical interview. All of the subjects hospitalized in a Burn
      Unit were referred for psychiatric examination to a psychiatric consultation
      liaison programme. Most of the patients suffered adjustment disorders (n = 40),
      and post-traumatic stress disorder (PTSD) was diagnosed in 5 cases. The carefully
      assessment of PTSD was an objective of the Study. There were no significant
      differences among patients with PTSD and Adjustment Disorder for severity and
      type of burn injuries. The discussion deals with PTSD is a frequent missed
      disorder by the medical staff of burn units, and also the importance of the
      patients subjective appraisal of the stressor as a factor precipitating PTSD.

PMID- 8553923
TI  - [The evolution of the concept of archetypes in Jungian psychology].
AB  - The concept of archetype is basic in the Junguian conception of the human mind.
      Without archetypes the Junguian theory of the collective unconscions is absurd.
      Jung himself recognized that the concept of archetype had originated the worst
      misunderstandings of his theories. Within Junguian schools there is an archetypal
      school which has originated archetypal conceptions quite apart from the initial
      junguian ideas. In this paper the evolution of the concept of archetype is
      studied, and its implications for the practice of Junguian psychotherapy are
      considered.

PMID- 8553924
TI  - [The discourse as the practice component. (The study of Foucault's theory of
      objects of discourse, represented in psychopathology)].
AB  - The subject is discourse; such discourse is far from a simple point of encounter
      (or disencounter) between a language, a significant system, and a wild, virginal
      reality that is distant from any word. Farm from being a mere actualization of a
      group of signs used to indicate "things per se-, to represent a reality that now,
      beforehand, and regardless of the language describes it as such, has a mute sense
      that awaits the moment of its expression; far from being, I say, words, mere
      words that fall softly on things to me them, transform them, form them? it
      regularly constitutes what is spoken. Thus discourse is something more, it does
      more than indicate, name, translate, express ... it produces reality; moreover,
      of this is the case, in theoretical knowledge, theory is not neutral or
      disinterested contemplation, but productive power, poetry... Therefore, the
      effects of discourse rather than its causes are what are expressed and what
      interests this philosopher is the action of Foucault's discourse, inasmuch as its
      practice is characterized by a group of hierarchical rules.

PMID- 8553925
TI  - [Neuroleptic malignant syndrome: a review of literature].
AB  - Neuroleptic malignant syndrome is characterized by altered consciousness, fever,
      extrapyramidal signs and autonomic instability. Although originally described in
      patients receiving neuroleptic drugs, this syndrome may also occur in patients
      who were taking a wide variety of medications. It is a rare and potentially
      lethal idiosyncratic reaction that occurs after therapeutic rather than toxic
      doses of neuroleptics drugs and is unrelated to the duration of therapy. The
      implications of dopaminergic disturbances underlying the mental illnesses
      involved are considered. Treatment of the neuroleptic malignant syndrome
      involves, first of all, supportive measures and withdrawal of the neuroleptic
      drugs therapy.

PMID- 8553926
TI  - Glen W. Hartman Lecture: Radiology Section of the National Medical Association.
      Centennial history of African-Americans in radiology.
AB  - It has not been an easy century for African-Americans in radiology, but many
      accomplishments have been achieved, often in the face of considerable adversity.
      Many, many important persons have been omitted from this essay. This section
      (Fig. 5) has supported progress through the years. May it continue the good work.

PMID- 8553927
TI  - Radiology in Nepal.
AB  - The joys of doing an international visiting professorship are the challenging
      environment and the enthusiasm of the indigenous students and physicians. Having
      previously taught radiology at the University of Nairobi, Kenya, for 4 months in
      1992, I felt prepared for the advanced diseases, limited supplies, broken
      equipment, and challenging environment that I would encounter in Nepal. The
      Radiology Outreach Foundation sponsored me (W. E. Brant) for 3 months to teach
      radiology at Tribhuvan University Teaching Hospital (TUTH) in Kathmandu in the
      spring of 1995. I was concerned about how effective my teaching would be, how
      well I could relate to the local conditions of practice, and whether my English
      only language skills would be sufficient. My hosts in Nepal proved as eager to
      teach me as to learn from me. I was captivated by the ability of the TUTH faculty
      to innovate. Nephrostomy drainage could be accomplished with a feeding tube or
      refashioned angiography catheter (Fig. 1). Complete aspiration of a hepatic
      abscess could and should be performed with a single needle at the time of
      diagnosis because the patient may never be able to return for follow up. One
      day's film review revealed every manifestation of pulmonary tuberculosis (TB), as
      well as worms in the bile ducts and hydatid cysts in the liver. Without CT
      scanning, sonography was the prime diagnostic tool. Although my prepared lectures
      were well received, teaching is best accomplished while the daily film stack and
      with sonography transducer in hand. English is understood and well spoken by
      almost all physicians and medical students in Nepal. In this article, we discuss
      the current practice of radiology in Nepal.

PMID- 8553928
TI  - HIV transmission during invasive radiologic procedures: estimate based on
      computer modeling.
AB  - OBJECTIVE: The primary purpose of this study was to estimate the risk of HIV
      transmission from physicians to patients during invasive radiologic procedures
      and to compare this estimate with those previously derived for surgical
      procedures so that policy on possible practice restrictions can be decided. The
      risk of HIV transmission from patient to physician, including cumulative career
      risk for interventional radiologists, was also estimated. MATERIALS AND METHODS:
      The risk of HIV transmission from physician to patient and vice versa was
      estimated with computer modeling techniques, using available data on prevalence
      of HIV infection, rates of injury during invasive radiologic procedures, and risk
      of viral transmission after an exposure. Cumulative career risk of occupational
      infection was estimated with a computer simulation model. RESULTS: If the
      physician's HIV status is unknown, the risk of transmission of HIV to a patient
      during a procedure is estimated to be 0.03 per million procedures (95% confidence
      interval, 0-3.8 per million procedures). If the physician is known to be HIV
      positive, the risk of transmission to a patient is estimated to be 7.5 per
      million procedures (95% confidence interval, 0-15.3 per million procedures). The
      estimated risk of transmission from patient to physician ranges from 0.03 to 7.5
      per million for a single procedure, and the cumulative risk of occupational HIV
      infection over 30 years is estimated to be 0.009-16%. CONCLUSION: The estimated
      risk of HIV transmission from physician to patient during invasive radiologic
      procedures is so low that global practice restrictions on HIV-infected
      interventional radiologists are not warranted. As recommended by the American
      Medical Association and the Centers for Disease Control, decisions on possible
      practice restrictions should be made on a case-by-case basis rather than a
      priori. The risk of HIV transmission from patient to physician is also low, but
      real. The cumulative career risk of occupational infection with HIV may vary
      widely based on individual circumstances and the patient population served.

PMID- 8553929
TI  - Prospective comparison of CT angiography of the legs with intraarterial digital
      subtraction angiography.
AB  - OBJECTIVE: The aim of this study was to determine the accuracy of CT angiography
      (CTA) with a single spiral acquisition for the diagnosis of arterial stenoses and
      occlusion in patients with peripheral vascular occlusive disease. SUBJECTS AND
      METHODS: In a prospective study, intraarterial digital subtraction angiography
      and i.v. CTA from the groin to the lower calves were performed on 50 patients
      with vascular occlusive disease. Maximum-intensity-projection images in multiple
      views were produced. The accuracy of CTA with and without analysis of the axial
      scans was determined with digital subtraction angiography as the standard.
      RESULTS: The sensitivities of CTA were 100% for the diagnosis of femoral artery
      occlusion, 100% for the detection of popliteal artery (including tibial-peroneal
      arterial trunk) occlusion, and 94% for the detection of tibial artery occlusion.
      The specificities were 100%, 99%, and 98%, respectively. When maximum-intensity
      projection images were interpreted without axial scans, sensitivities were 98%,
      85%, and 92% and specificities were 100%, 99%, and 97%, respectively. For the
      accurate grading of high-grade (75-99%) stenoses of the superficial femoral
      artery and the popliteal artery (including tibial-peroneal arterial trunk), the
      sensitivities of CTA were 88% and 73% and the specificities were 94% and 100%,
      respectively. When maximum-intensity-projection images alone were used, the
      sensitivities for the correct grading of high-grade stenoses were 58% and 36% and
      the specificities were 99% and 100%, respectively. CONCLUSION: CTA from the groin
      to the lower calves is feasible, and the short examination time is a
      significantly advantage over the time required for other noninvasive techniques.
      CTA is particularly accurate in the depiction of femoral artery occlusions.
      Maximum-intensity-projection images are useful, but analysis of axial scans is
      more accurate for the grading of arterial stenoses. The results of CTA are
      encouraging enough to warrant further studies. A CTA protocol covering the pelvic
      and pedal vessels remains to be established and evaluated.

PMID- 8553930
TI  - Intraarterial pressure measurements during angiographic evaluation of peripheral
      vascular disease: techniques, interpretation, applications, and limitations.
AB  - Many operative and percutaneous procedures are available for the treatment of
      occlusive disease involving the lower-extremity arterial system. Peripheral
      vascular disease involving the aorta and lower-extremity vessels usually is
      attributable to atherosclerosis. The lower-extremity arterial supply is divided
      segmentally into the inflow (aortoiliac) and outflow (femoropopliteal and
      tibioperoneal) vessels. Given the length of the lower-extremity vascular system,
      the propensity for multifocal disease, and the possibility of a nonvascular cause
      for a patient's symptoms, both localization of disease in arterial segments and
      determination of the hemodynamic impact of diseased sites are important for
      judicious treatment planning. This review focuses on the use of intraarterial
      pressure measurement as an adjunct to angiography and intravascular intervention
      in evaluating the significance of arterial occlusive disease in lower-extremity
      arteries.

PMID- 8553931
TI  - Compression sonography in patients with indeterminate or low-probability lung
      scans: lack of usefulness in the absence of both symptoms of deep-vein thrombosis
      and thromboembolic risk factors.
AB  - OBJECTIVE: We sought to determine whether compression sonography could be
      eliminated in the evaluation of patients who lacked both thromboembolic risk
      factors and symptoms of deep-vein thrombosis and who had an indeterminate or low
      probability lung scan. MATERIALS AND METHODS: The medical records of 155
      consecutive patients who underwent bilateral lower-extremity sonography after an
      indeterminate or low-probability lung scan were reviewed. The presence of
      thromboembolic risk factors and deep-vein thrombosis symptoms and the result of
      sonography were recorded. Patients were divided into two groups: group 1
      consisted of patients with either thromboembolic risk factors or deep-vein
      thrombosis symptoms, and group 2 consisted of patients without thromboembolic
      risk factors and without deep-vein thrombosis symptoms. The incidences of deep
      vein thrombosis in groups 1 and 2 were compared by use of a two-tailed Fisher's
      exact test. RESULTS: Thromboembolic risk factors or deep-vein thrombosis symptoms
      were found in 109 of 155 patients (70%) (group 1). Deep-vein thrombosis was found
      in nine of 108 patients (8%) in group 1. Both thromboembolic risk factors and
      deep-vein thrombosis symptoms were absent in 47 of 155 patients (30%) (group 2).
      Deep-vein thrombosis was found in none of 47 patients (95% confidence interval, 0
      8%) in group 2. The difference in the incidences of deep-vein thrombosis in
      groups 1 and 2 approached statistical significance (p = .0579). The negative
      predictive value of the absence of both thromboembolic risk factors and deep-vein
      thrombosis symptoms in excluding deep-vein thrombosis was 100% (95% confidence
      interval, 93-100%). CONCLUSION: If both symptoms of deep-vein thrombosis and
      thromboembolic risk factors are absent, the usefulness of lower-extremity
      sonography in detecting deep-vein thrombosis in patients with an indeterminate or
      low-probability lung scan is low. The manner in which these findings may be used
      to modify individual practice patterns will undoubtedly depend on the rate of
      detection of deep-vein thrombosis at a given institution.

PMID- 8553932
TI  - High-flow priapism in a child: treatment with superselective embolization.

PMID- 8553933
TI  - Helical (spiral) CT of the upper airway with three-dimensional imaging: technique
      and clinical assessment.
AB  - OBJECTIVE: The purpose of this study was to evaluate the application of helical
      CT-generated three-dimensional images of the upper airway. MATERIALS AND METHODS:
      Thirty patients, 10 healthy and 20 with upper-airway disease, were studied with
      helical CT (5-mm collimation). Overlapping images at 2-mm intervals were
      retrospectively generated. In the group of healthy patients, two radiologists in
      independently compared overlapping with nonoverlapping images, ranked confidence
      in identifying small airway structures on a scale of 1-5, and tabulated the
      number of images demonstrating these structures. In the 20 patients with disease,
      three-dimensional (3D) surface models were rendered on an independent workstation
      and were reviewed by two radiologists and one otolaryngologist for image quality,
      appreciation of lesion morphology, and ability to judge lesion extent, using a
      similar scale. A phantom was used to optimize parameters for the 3D
      reconstructions. RESULTS: Viewing of the retrospectively generated overlapping
      images increased by 122% the number of images in which laryngeal and
      hypopharyngeal structures could be identified (p < .01). Image confidence scores
      for the radiologists averaged 3.3 for nonoverlapping and 4.0 for overlapping (p <
      .05). Radiologists and otolaryngologist rated the quality of the 3D images
      equally. The otolaryngologist's assessment of the value of the models for
      understanding the lesion morphology was 3.5 compared with the radiologists
      assessment of 2.5; and for judging the lesion extent, the otolaryngologist's
      assessment was 3.8 compared with 2.7 for the radiologist, a statistical
      significance of p < .01. CONCLUSION: Helical CT with the application of
      overlapping images and 3D reconstructions significantly assists the understanding
      of upper-airway disease.

PMID- 8553934
TI  - High-resolution chest CT in systemic lupus erythematosus.
AB  - OBJECTIVE: The purpose of our study was to identify high-resolution CT (HRCT)
      findings in patients with systemic lupus erythematosus (SLE) and to determine
      their significance by correlation with clinical findings, plain chest
      radiography, and pulmonary function testing. SUBJECTS AND METHODS: Thirty-four
      patients with documented SLE were prospectively studied. All patients had plain
      chest radiography (posteroanterior and lateral) thoracic spiral CT, HRCT, and
      pulmonary function testing performed. RESULTS: HRCT abnormalities were identified
      in 24 patients (70%), pulmonary function abnormalities were present in only 14
      patients (41%), and the plain chest radiograph was abnormal in only 8 patients
      (24%). The most common CT findings were: interstitial lung disease (n = 11),
      bronchiectasis (n = 7), mediastinal or axillary lymphadenopathy (n =6), and
      pleuropericardial abnormalities (n =5). No correlation was found between disease
      activity, duration of disease, chest symptoms, drug therapy, smoking history, and
      the presence of abnormal HRCT findings. More importantly, no correlation was
      found between pulmonary function abnormalities and the presence or grade of
      interstitial lung disease or bronchiectasis as determined by HRCT. CONCLUSION:
      The results of this study, the first to describe the HRCT findings in SLE,
      suggest that airways disease, lymphadenopathy, and interstitial lung disease are
      common thoracic manifestations of SLE, whereas pleural abnormalities are less
      common than previously suggested. HRCT evidence of airways disease and
      interstitial lung disease was frequently present despite an absence of symptoms,
      a normal chest radiograph, and normal pulmonary function testing. HRCT provides a
      sensitive and noninvasive technique for detecting pulmonary involvement in SLE,
      with the added advantage that it can be performed in all patients, including
      those too compromised to undergo a surgical procedure. In patients with advanced
      disease, HRCT permits procedures such as bronchoalveolar lavage and lung biopsy
      to be directed toward areas of particular interest.

PMID- 8553935
TI  - Pleuropulmonary blastoma with vascular invasion.

PMID- 8553936
TI  - Peribronchovascular interstitium of the pulmonary hilum: normal and abnormal
      findings on thin-section electron-beam CT.
AB  - The peribronchovascular interstitium, including bronchial vessels and lymphatic
      channels, is an important anatomic component of the lung, especially the
      pulmonary hilum [1-3] (Fig.1). Various pathologic processes involve and spread
      along this interstitium [4, 5]. Although it has been difficult to accurately
      evaluate the morphologic changes occurring in the peribronchovascular
      interstitium with conventional CT or MR imaging [6], spiral CT and electron-beam
      CT can show these changes clearly and consistently [7, 8]. A judgement as to
      whether the peribronchovascular interstitium is normal or abnormal is necessary
      for the CT diagnosis of pulmonary hilar lesions. In this assay, the normal
      peribronchovascular interstitium and various pathologic processes involving this
      interstitium are shown as they appear on thin-section electron-beam CT scans.

PMID- 8553937
TI  - Comparison of upright inspiratory and expiratory chest radiographs for detecting
      pneumothoraces.
AB  - OBJECTIVE: Expiratory films are regarded as being superior to inspiratory films
      for pneumothorax detection, yet this has not been proved. In the current study,
      we compared inspiratory versus expiratory chest radiographs for pneumothorax
      detection. MATERIALS AND METHODS: Eighty-five paired inspiratory and expiratory
      radiographs with pneumothoraces and 93 pairs without pneumothoraces were randomly
      arranged and reviewed independently by three radiologists. A score of 1-5 was
      assigned for each hemithorax (5 = definite pneumothorax, 1 = definitely no
      pneumothorax). Results were compared for inspiration and expiration using
      receiver operating characteristic (ROC) analysis. RESULTS: The average area under
      the ROC curves for all readers was .973 for inspiration and .972 for expiration
      (nonsignificant). McNemar's test and an alpha level of .05 also yielded no
      significant difference in sensitivity and specificity. Four of the 85 cases were
      scored as definite pneumothorax on inspiration and as definitely not on
      expiration by all readers, and three of the 85 cases were scored as definite
      pneumothorax on expiration and as definitely not on inspiration. CONCLUSION:
      Inspiratory and expiratory upright films are equally sensitive for pneumothorax
      detection. Given the limitations of expiratory films, inspiratory films are
      recommended as the initial examination of choice for pneumothorax detection.

PMID- 8553938
TI  - Detection and estimation of the volume of pneumothorax using real-time
      sonography: efficacy determined by receiver operating characteristic analysis.
AB  - OBJECTIVE: The purpose of this study was to determine the efficacy of real-time
      sonography for the detection and estimation of the volume of pneumothorax using
      receiver operating characteristic (ROC) analysis in 27 patients evaluated by five
      radiologists using previously described sonographic findings. MATERIALS AND
      METHODS: Bilateral chest sonograms were obtained in 27 patients after we
      performed 26 needle biopsies of the lung and two transcostal biopsies of lesions
      at the dome of the liver. Thirteen unilateral pneumothoraces were found on
      radiographs done at the time of the sonograms. The sonograms were recorded on
      videotape and later viewed by five blinded readers who scored each hemithorax
      independently as to the likelihood and size of pneumothorax. From these
      interpretations we were able to calculate ROC curves and standard accuracy
      statistics for each observer and for pooled data. The results were correlated
      with the findings on chest radiographs, which were used to verify the diagnoses.
      RESULTS: The area under the ROC curves ranged from 0.63 to 0.79 in detecting any
      pneumothorax. The area under the ROC curve derived by pooling readers and
      hemithoraces using the jackknife method was 0.73. The average sensitivity of the
      five observers fro pneumothorax was 73%, the specificity was 68%, and the
      negative and positive predictive values were 89% and 40%, respectively. No
      significant correlation was found between readers' estimates of pneumothorax size
      made on the basis of sonographic findings and actual size as ascertained from
      chest radiographs. CONCLUSION: Real time sonography is useful to localize known
      pneumothorax but cannot be used to exclude the diagnosis. Moreover, sonography
      has a significant false-positive rate and is of no use in estimating the volume
      of a pneumothorax.

PMID- 8553939
TI  - Steam inhalation causing delayed airway occlusion.

PMID- 8553940
TI  - The proposed new international TNM staging system for malignant pleural
      mesothelioma: application to imaging.
AB  - Malignant pleural mesothelioma (MPM) is an uncommon and usually fatal primary
      neoplasm of the pleura. In the past, response to standard therapy has been poor
      [1-3], but recent studies suggest that some patients may benefit from various
      therapeutic options, including surgical resection, combined technique treatment,
      and immunotherapy [4-7]. With improvements in therapy, an accurate, widely
      accepted staging system will be important in selecting homogeneous groups of
      patients for entry into clinical trials. Multiple staging systems have previously
      been proposed for MPM, but none are universally used [8].

PMID- 8553941
TI  - Radiographic appearance of central venous catheters.
AB  - Central venous catheters (CVCs) are defined as venous access devices whose tips
      terminate in the superior or inferior vena cava, regardless of insertion site.
      CVCs allo reliable, painless, and repeated entry into the venous system and are
      commonly used for the administration of IV therapy, parenteral nutrition, and
      blood products as well as for the periodic blood sampling, hemodynamic
      monitoring, and hemodialysis. Catheter composition and design vary and depend on
      the duration of intended use and specific functions required. The purpose of this
      essay is to illustrate commonly used catheters, discuss factors governing
      catheter selection, and review important catheter-related complications.

PMID- 8553942
TI  - Accessory breast tissue in an unusual location.

PMID- 8553944
TI  - Poland's syndrome: a mammographic presentation.

PMID- 8553943
TI  - Percutaneous core biopsy of the breast: effect of operator experience and number
      of samples on diagnostic accuracy.
AB  - OBJECTIVE: The purpose of our study was to assess the degree of operator
      experience and the number of core biopsy samples required to achieve an accurate
      histologic diagnosis for each of five common mammographically defined lesions,
      using percutaneous core breast biopsy performed on a dedicated prone biopsy
      table. SUBJECTS AND METHODS: A prospective multisite study was performed that
      involved nine institutions (academic and private) with experienced breast
      radiologists and the use of dedicated prone biopsy table units with digital
      assistance and standardized protocol. Asymptomatic women evaluated during a 2
      year study period were assigned a mammographic diagnosis reported in a manner
      prescribed by the American College of Radiology Breast Imaging Reporting and Data
      System lexicon. Mammographic lesions evaluated included masses, masses with
      calcifications, clustered calcifications, focal asymmetries, and architectural
      distortions. Where histologic diagnosis was indicated, core biopsy was performed
      with five individual samples obtained and sequentially analyzed. Two hundred
      thirty patients had immediate excisional biopsy, the results of which provided
      the basis for a statistical analysis to compare the accuracy of each sequential
      core biopsy sample with surgical results. Statistical analysis was also done to
      ascertain the accuracy of core biopsy diagnosis as a function of operator
      experience. RESULTS: Trends toward increasing accuracy were observed by
      increasing the number of core biopsies for each of five types of mammographically
      defined lesions, especially for clustered calcifications. Statistically
      significant increased accuracy was observed when the number of biopsies was
      increased beyond one (p = .003). Trends toward increased accuracy with more
      experience were observed for all lesions, especially for calcifications. Of the
      230 lesions studied with immediate surgical validation, more than 80% of all
      lesions except clustered calcifications (75%) were diagnosed on the basis of two
      core biopsies; accuracy after five biopsies was 98% for masses, 91% for
      calcifications, 100% for masses with calcification, 100% for focal asymmetries,
      and 86% for architectural distortions. CONCLUSIONS: Accuracy of diagnosis based
      on the results of percutaneous core breast biopsy improved with an increase in
      the number of core biopsy samples obtained for any given lesion seen on
      mammograms and with increased experience in performing the procedure. Five
      samples yielded an overall diagnostic accuracy of 97%. Familiarity with expected
      accuracy from this procedure for different mammographic lesions and following
      increased experience may assist physicians in planning patient management.

PMID- 8553945
TI  - Pseudoangiomatous stromal hyperplasia: mammographic and sonographic appearances.
AB  - OBJECTIVE: Pseudoangiomatous stromal hyperplasia is a benign, localized form of
      stromal overgrowth with a probable hormonal etiology. Our purpose is to describe
      the mammographic, sonographic, and clinical features of this entity. MATERIALS
      AND METHODS: A retrospective review of breast imaging studies and demographic
      information for seven patients identified as having pseudoangiomatous stromal
      hyperplasia was performed. The patients were chosen from a 1-year period during
      which 1661 breast biopsies were performed. RESULTS: The patients were 36-61 years
      old. Six were premenopausal, and the one postmenopausal woman was on hormone
      replacement therapy. Three patients wee evaluated palpable breast lumps, and four
      were asymptomatic. All seven women had noncalcified masses that measured 1.1-11
      cm and that were visible by mammography. The border characteristics were as
      follows: three masses were well circumscribed, two were partly circumscribed, and
      two were indistinct, probably because they were obscured by overlying parenchyma.
      Sonography was performed for five patients; lesions were visible in four. All
      four of these lesions were solid and circumscribed. Five of the masses had
      increased in size since earlier studies, and one palpable mass was found by
      physical examination to have grown over time. Two patients had a local recurrence
      of pseudoangiomatous stromal hyperplasia. Surgical excision was performed for
      three patients, large-core biopsy was performed for three patients, and both
      surgery and large-core biopsy were performed for one patient. CONCLUSION:
      Pseudoangiomatous stromal hyperplasia should be included in the differential
      diagnosis of a circumscribed or partially circumscribed mass, especially in the
      premenopausal population. These masses often grow over time and can recur
      locally. Pathologic diagnosis of the lesion may be difficult unless the
      pathologist is aware of the presence of a mass lesion and appreciates the stromal
      changes characteristic of such a lesion.

PMID- 8553946
TI  - Functional abnormalities of the pharynx: a prospective analysis of radiographic
      abnormalities relative to age and symptoms.
AB  - PURPOSE: To determine the prevalence and severity of functional abnormalities of
      the pharynx relative to patient age and symptoms. MATERIALS AND METHODS:
      Radiographic evaluation of the pharynx was performed in 110 consecutive
      outpatients aged 19-84 years old who had no previous surgery of the larynx,
      pharynx, or esophagus. Each patient completed a symptom data sheet, and we
      reviewed medical records to determine the main indication for each examination.
      Videofluoroscopy and static filming in frontal and lateral positions were done
      with 20-ml barium boluses. We then evaluated functional abnormalities and
      classified abnormal findings by type and severity. RESULTS: We categorized
      patients by age into three groups: less than 40 years old (n=31), between 40 and
      60 years old (n =42), and greater than 60 years old (n=37). We found a
      significant increase in the prevalence (23%, 36%, 57%, respectively) and severity
      of functional abnormalities of the pharynx in older patients (p < .05). Laryngeal
      penetration, aspiration, pharyngeal stasis, and cricopharyngeal bar were the main
      abnormalities found in the two older groups. However, we found no correlation
      between functional abnormalities of the pharynx and symptoms and indications (p >
      .05). CONCLUSION: Functional abnormalities of the pharynx increased in prevalence
      and severity with age. Often these findings were not related to specific
      pharyngeal symptoms and must be interpreted cautiously in older patients.

PMID- 8553947
TI  - The magic tilt method of tubeless enteroclysis: a modification to the gas
      enhanced barium small-bowel examination.

PMID- 8553948
TI  - Endoanal coil in MR imaging of anal fistulas.

PMID- 8553949
TI  - Hepatic tumors treated by cryosurgery: normal CT appearance.
AB  - OBJECTIVE: An understanding of the normal appearance of hepatic tumors treated
      with cryosurgery is essential for accurately distinguishing normal postoperative
      changes from potential complications such as hepatic abscess or infarct, which
      may necessitate further interventions. The purpose of this study was to
      characterize the normal spectrum of CT findings after cryoablation of hepatic
      tumors. SUBJECTS AND METHODS: The CT scans of 14 patients who had undergone
      hepatic cryoablation 4-16 days (mean, 7 days) before scanning were reviewed by
      three radiologists. None of these patients had postprocedural complications that
      necessitated intervention (e.g. abscess, infarct, or hemorrhage). Indications for
      cryoablation included primary hepatic tumors in four patients and hepatic
      metastases in 10 patients. CT findings were correlated with surgical findings in
      a lesion-by-lesion manner to ensure that only cryolesions were included in the
      analysis. RESULTS: Twenty-eight cryolesions from 3 to 11 cm maximum diameter
      (mean, 7 cm) were detected on CT scans. All cryolesions were primarily hypodense
      and extended to the liver capsule. Ten (36%) of 28 lesions contained air, and 26
      (93%) of 28 lesions contained hemorrhage. Thirteen (54%) of 24 lesions evaluated
      with i.v. contrast material showed peripheral enhancement. Cryolesions were
      primarily wedge shaped (54%), round (29%), or teardrop shaped (21%). One
      iatrogenic portosystemic shunt was detected. Other associated findings included
      subcapsular hemorrhage (29%), perihepatic fluid collections (43%), right-sided
      pleural effusion (93%), left-sided pleural effusion (64%), atelectasis of one or
      both lungs (93%), and ascites (7%). CONCLUSION: The postoperative CT appearance
      of the liver in patients who underwent hepatic cryoablation without complications
      mimics that seen in the liver of patients with hepatic abscesses or infarcts. The
      CT appearance of the liver in patients undergoing cryosurgery needs to be
      carefully analyzed to avoid confusing normal findings related to the procedure
      with those related to procedural complications, it may be impossible to
      differentiate hepatic complications from normal postoperative changes on the
      basis of CT findings in many of these patients.

PMID- 8553950
TI  - Dynamic MR imaging and early-phase helical CT for detecting small intrahepatic
      metastases of hepatocellular carcinoma.
AB  - OBJECTIVE: We performed a study to evaluate the sensitivities of multislice
      dynamic MR imaging and early-phase helical CT as noninvasive methods for
      detecting small intrahepatic metastases of hepatocellular carcinomas. MATERIALS
      AND METHODS: Dynamic and spin-echo MR imaging and early- and delayed-phase
      helical CT of the liver were performed for patients with multiple hepatocellular
      carcinomas before transcatheter arterial chemoembolization. Forty-nine patients
      had 242 intrahepatic metastases less than 3 cm in diameter. Using iodized-oil CT
      after transcatheter arterial chemoembolization as a gold standard, the
      sensitivity of MR imaging for detecting intrahepatic metastases was compared with
      that of CT. RESULTS: Of the 242 nodules, 225 were diagnosed as hepatocellular
      carcinomas by iodized-oil CT. Of these, dynamic MR imaging and early-phase CT
      were significantly superior to those of spin-echo MR imaging (p < .0001) and
      delayed phase CT (p < .0001) for tumors less than 1 cm in diameter. CONCLUSION:
      Dynamic MR imaging and early-phase CT of the liver are the most sensitive
      noninvasive means of detecting small intrahepatic metastases of hepatocellular
      carcinoma before and after treatment.

PMID- 8553951
TI  - Time-of-flight MR angiography of the portal venous system: value compared with
      other imaging procedures.
AB  - OBJECTIVE: The purpose of this study was to retrospectively compare two
      dimensional time-of-flight MR angiography with other imaging procedures in the
      evaluation of the portal venous system in 152 consecutive patients. MATERIALS AND
      METHODS: The findings on MR angiography performed on 152 patients to depict
      breath-hold, two-dimensional time of flight MR angiography. Selective arterial
      presaturation, bolus tracking, and three-dimensional reconstruction were used
      routinely. Findings were correlated with findings on sonography (104 patients),
      CT (8 patients), and conventional digital subtraction angiography (19 patients)
      as well as surgery (23 patients). RESULTS: Agreement between results of MR
      angiography and alternative types of imaging was excellent (99%). Agreement with
      sonography (100 of 104), CT (8 of 8), conventional angiography (18 of 19), and
      surgery (23 of 23) was good. Visualization of varices and spontaneous shunts by
      MR angiography was superior to that by other imaging techniques. CONCLUSION: Our
      experience shows that time-of-flight MR angiography is reliable and accurate for
      depicting portal venous anatomy. MR angiography shows vessels that are not
      visible with sonography. Complicated pathology is clearly visualized in a way
      that is not possible with other techniques.

PMID- 8553952
TI  - Ring enhancement in ultrasmall superparamagnetic iron oxide MR imaging: a
      potential new sign for characterization of liver lesions.
AB  - OBJECTIVE: We performed this study to evaluate the incidence and significance of
      ring enhancement after i.v. administration of an ultrasmall superparamagnetic
      iron oxide (USPIO) particle (Code 7227), a reticuloendothelial contrast agent
      with potential use as a blood-pool agent, for characterizing focal hepatic
      lesions. SUBJECTS AND METHODS: Conventional T1-weighed imaging, fat-suppressed T1
      weighted imaging, conventional T2-weighted imaging, and fast T2-weighted imaging
      of the liver were obtained in 27 patients with 43 liver lesions before and after
      i.v. administration of a USPIO preparation. All lesions were larger than 1 cm; 29
      were malignant and 14 were benign. Diagnosis was confirmed in all cases, either
      pathologically (19 patients) or by follow-up examination (eight patients). Two
      readers independently evaluated each pulse sequence for the presence of ring
      enhancement of hepatic lesions. RESULTS: Ring enhancement was noted only on T1
      weighted images, with no ring enhancement evident on T2-weighted images. Twenty
      of 43 (47%) lesions showed ring enhancement, including 18 of 29 (62%) malignant
      lesions and two of 14 (14%) benign lesions (p < .011); Wilcoxon signed rank
      test). Fat-suppressed T1-weighted imaging showed ring enhancement better than or
      equal to conventional T1-weighted imaging in all cases, with ring enhancement of
      15 of 18 (83%) malignant lesions and two of two benign lesions better
      demonstrated on fat-suppressed T1-weighted imaging sequences (p < or = .025).
      CONCLUSION: Ring enhancement after i.v. administration of Code 7227 is a frequent
      finding seen more often with malignant than benign lesions, potentially
      identifying a new MR imaging feature for the characterization of liver lesions.
      The identification of ring enhancement on T1-weighted images attests to the
      significant blood-pool effects of USPIO particles.

PMID- 8553953
TI  - Characterization of adnexal masses: combination of color Doppler and conventional
      sonography compared with spectral Doppler analysis alone and conventional
      sonography alone.
AB  - OBJECTIVE: To evaluate the importance of color Doppler combined with conventional
      sonography in characterizing adnexal masses and to compare the results with those
      of spectral Doppler analysis alone and conventional sonography alone. MATERIALS
      AND METHODS: One hundred and fifteen women with 132 adnexal masses (98 benign,
      three borderline, and 31 malignant) were prospectively studied with conventional
      and Doppler sonography (transabdominal in all patients and transvaginal in 111).
      Three methods differentiated benign from borderline and malignant masses. In the
      first, conventional sonography was used. In the second, conventional sonography
      was combined with color Doppler. In this method, the presence of color flow in an
      echogenic portion classified as indeterminate or malignant by conventional
      sonography indicated malignancy; the absence of color flow in an echogenic
      portion classified as indeterminant or malignant at conventional sonography
      indicated benignancy; the presence or absence of color flow in a regular wall or
      septum indicated benignancy. The third method used spectral Doppler analysis.
      Malignancy was indicated by a resistive index (RI) less than or equal to 0.4, a
      pulsatility index (PI) less than or equal to 1, or a peak systolic velocity (PSV)
      greater than or equal to 15 cm/sec. RESULTS: Using conventional sonography alone,
      accuracy was 83%, sensitivity was 88%, and specificity was 82%. Using
      conventional sonography and color Doppler, accuracy was 95%, sensitivity was 88%,
      and specificity was 97%. Using spectral Doppler analysis and an RI less than or
      equal to 0.4, accuracy was 77%, sensitivity was 18%, and specificity was 98%. For
      a PI less than or equal to 1, accuracy was 68%, sensitivity was 71%, and
      specificity was 67%. For a PSV greater than or equal to 15 cm/sec, accuracy was
      72%, sensitivity was 47%, and and specificity was 81%. CONCLUSION: Adding color
      Doppler to conventional sonography produced a specificity and positive predictive
      value higher than those of conventional sonography alone. Specificity increased
      from 82% to 97% (p < .001), and positive predictive value increased from 63% to
      91%. RI, PI, and PSV were of limited value.

PMID- 8553954
TI  - Adrenal myelolipoma.
AB  - In 1905, Gierke [1] first described the occurrence of a tumor in the adrenal
      composed of mature fat and mixed myeloid and erythroid cells, subsequently termed
      "formations myelolipomatoses" by Oberling [2] in 1929.

PMID- 8553955
TI  - Pelvic lesions in patients with treated cervical carcinoma: efficacy of
      pharmacokinetic analysis of dynamic MR images in distinguishing recurrent tumors
      from benign conditions.
AB  - OBJECTIVES: Dynamic MR image series were analyzed with a pharmacokinetic two
      compartment model. To preserve the spatial resolution of the dynamic MR images,
      the pharmacokinetic parameters were computed pixel by pixel, color coded, and
      superimposed on conventional MR images (pharmacokinetic mapping). The efficacies
      of pharmacokinetic mapping and conventional MR imaging in distinguishing between
      recurrent tumors and benign conditions in patients who have pelvic lesions after
      treatment of cervical carcinoma were compared. MATERIALS AND METHODS: Twenty-one
      women with 24 suspected pelvic lesions and a history of treated cervical
      carcinoma (stages IB-IIIA) were included in this study. Patients had been treated
      before MR imaging with surgery or irradiation alone (eight patients) or a
      combination of the two (13 patients). Patients were referred because of our
      findings from CT examinations and/or clinical examinations. Of 24 suspected
      lesions, 17 were histologically verified as tumor recurrences and seven were
      classified as benign masses (histologically diagnosed as fibrosis and granulation
      tissue). T1- and T2-weighted spin-echo images were interpreted by three
      observers. During and after constant-rate infusion of gadopentetate dimeglumine,
      the kinetics of lesion response were determined with a strongly T1-weighted
      saturation recovery turbo-fast low-angle shot sequence. The signal-time curves
      for the suspected lesions were analyzed within the framework of a pharmacokinetic
      two-compartment model and displayed as color-coded images. The calculated
      pharmacokinetic parameters (amplitude [A] and tissue distribution time [t21])
      were evaluated retrospectively to obtain optimal threshold values for
      differentiating malignant lesions from benign lesions. RESULTS: Analysis of the
      pharmacokinetic mapping data showed significantly shorter (p < .005) and stronger
      (p < .001) contrast medium enhancement of malignant lesions (t21, 24 sec; A, 1.5
      arbitrary units) than of benign lesions (t21, 65 sec; A, 0.7), resulting in a
      sensitivity of 100%, a specificity of 88%, and an accuracy of 96%. Interpretation
      of the lesions on conventional T2-weighted MR images resulted in a sensitivity of
      90%, a specificity of 38%, and an accuracy of 74%. CONCLUSION: Analysis of color
      coded pharmacokinetic maps is more effective than conventional MR imaging in
      distinguishing between malignant and benign conditions in patients who have
      pelvic lesions after treatment of cervical carcinoma.

PMID- 8553956
TI  - CT cystoscopy: an innovation in bladder imaging.

PMID- 8553957
TI  - MR imaging of the anterior cruciate ligament: frequency of discordant findings on
      sagittal-oblique images and correlation with arthroscopic findings.
AB  - OBJECTIVE: The purposes of this study were to determine the frequency of
      discordant MR findings of the anterior cruciate ligament (ACL) using sagittal
      oblique images and the arthroscopic integrity of the ACL in knees with a
      discordant MR appearance. MATERIALS AND METHODS: The frequency of discordant MR
      features was determined by independently reviewing the sagittal-oblique images of
      53 consecutive patients undergoing subsequent arthroscopic surgery. The first 25
      consecutive knees were examined using a conventional, dual-echo, T2-weighted spin
      echo (SE) sequence; the subsequent 28 consecutive knees were examined using both
      a T1-weighted SE(T1) and a fat-suppressed, fast spin-echo (FSE) T2-weighted
      sequence. Two examiners who were unaware of patient identification and
      arthroscopic results evaluated only the sagittal images that included the ACL.
      Each reviewer graded the ACL as torn or intact. The MR appearance was considered
      discordant when one MR sequence showed disrupted or poorly seen ACL fibers and
      the other sequence showed intact ACL fibers. The arthroscopic integrity of the
      ACL was determined for the 20 knees with a discordant MR appearance. RESULTS: A
      discordant MR appearance of the ACL was seen in 20 of the 53 knees (38%),
      including 10 knees evaluated using conventional T2-weighted sequences (40%) and
      10 knees using T1/FSE T2 (36%) sequences. Arthroscopic examination of these knees
      showed intact ACL fibers in all 20 knees; the ACL was normal in 18 knees and a
      partial tear was questioned in two knees. CONCLUSION: A discordant appearance of
      the ACL was frequently encountered (38%) using either conventional T2-weighted
      sequences or T1 and FSE MR sequences in the sagittal-oblique plane. Intact ACL
      fibers were found during arthroscopy in all 20 knees with a discordant MR
      appearance.

PMID- 8553958
TI  - Percutaneous skeletal aspiration and core biopsy: complementary techniques.
AB  - OBJECTIVE: Although core biopsy is the standard for percutaneous bone biopsy in
      most other organs aspiration biopsy is frequently performed. We prospectively
      evaluated 138 patients with skeletal lesions, performing both core and aspiration
      biopsies to determine if these techniques have a complementary role. SUBJECTS AND
      METHODS: Over a 2-year period, 138 consecutive patients underwent skeletal
      biopsy. In each patient, two or three histologic cores were obtained
      percutaneously using standard techniques followed by a single aspiration pass
      with a 22-gauge spinal needle and 20 cc of negative pressure. Histologic and
      cytologic evaluations of cores and aspirates were interpreted according to usual
      pathologic and cytologic criteria. Results were classified as matches (positive
      or negative), mismatches (aspiration or core only positive), mismatches (either
      aspiration or core more specific), insufficient samples, inaccurate diagnoses,
      and both false-negative. RESULTS: Twenty-eight patients had specific neoplasms
      diagnosed on both core and aspiration biopsy, and 40 patients were negative on
      both. The diagnosis was made only by core in 17 and only by aspiration in 11.
      Core was more specific in 11, and aspiration was more specific in seven. There
      were three insufficient cores and 18 insufficient aspiration specimens. One false
      negative result was seen by both techniques, and the cytology of two aspiration
      biopsies was misinterpreted. CONCLUSION: A complementary role exists for
      aspiration and core skeletal biopsy, and we suggest both should be routinely
      performed.

PMID- 8553959
TI  - Direct coronal CT of the wrist: helical acquisition with simplified patient
      positioning.

PMID- 8553960
TI  - A regional approach to the classic metaphyseal lesion in abused infants: the
      proximal tibia.
AB  - OBJECTIVE: The purpose of this study was to systematically analyze the spectrum
      of morphologic alterations of the classic metaphyseal lesion (CML) involving the
      proximal tibia of abused infants and to identify features that aid in the
      radiologic diagnosis and assessment of healing. MATERIALS AND METHODS: Thirty-one
      infants who died with evidence of inflicted skeletal injury were studied with
      high-detail skeletal surveys, resected specimen radiography, and histopathologic
      analysis. The number of fractures identified, the portions of the proximal tibial
      metaphyses involved, and the age of the lesions were assessed. RESULTS: Seventeen
      proximal tibial CMLs were noted. They were bilateral in six instances and
      unilateral in five. When the lesion was visible radiographically, it always
      involved the medial aspect of the metaphysis, with involvement of the lateral
      metaphyseal margin in more extensive injuries. Fractures tended to be less
      conspicuous when acute and were more easily recognizable with healing, especially
      with specimen radiography. Histologically, the fracture line consistently
      undercut the medial subperiosteal bone collar. Extension of hypertrophic
      chondrocytes from the growth plate into the region of fracture was a common
      finding. CONCLUSION: The CML of the proximal tibia has distinctive radiologic and
      histopathologic characteristics that relate to the anatomy of the region. Because
      the proximal tibia is a common site for this strong indicator of infant abuse,
      the region should be carefully evaluated with well-collimated, high-detail
      skeletal radiographs in all cases of suspected infant abuse.

PMID- 8553961
TI  - Sonographic anatomy of the developing cerebellum: normal embryology can resemble
      pathology.
AB  - OBJECTIVE: The aims of this study were to evaluate sonographically observable
      fetal cerebellar development by use of MR image and anatomic correlations to
      determine what aspects of this development can be visualized by sonography and to
      define the normal sonographic appearance of cerebellar development to assist in
      the differentiation of normal development from pathologic development during
      prenatal sonography. MATERIALS AND METHODS: The posterior fossae of 19 normal,
      whole, fixed fetal specimens of 11-21 weeks' gestational age were imaged by
      sonography and MR imaging. Images were correlated with anatomic atlases and
      anatomic sections. RESULTS: By 13-14 weeks, both sonography and MR imaging
      demonstrated the vermis between the hemispheres rostrally, but the caudal vermis
      was undeveloped. Although visualized on MR images, the caudal fourth ventricular
      roof was not yet appreciated on sonograms, giving the false impression of
      communication between the fourth ventricle and the cisterna magna. Separation of
      these CSF spaces was not appreciated at all levels sonographically until 16
      weeks. CONCLUSIONS: The sonographic appearance of normal cerebellar development
      can resemble pathology early in the second trimester. Caution is warranted in
      making an early diagnosis of fetal cerebellar dysgenesis.

PMID- 8553962
TI  - Imaging manifestations of cat-scratch disease.
AB  - Cat-scratch disease affects an estimated 22,000 people in the United States each
      year, more than half of whom are children or adolescents [1]. It is caused by
      Bartonella henselae, a gram-negative bacillus usually introduced by the scratch
      of a cat [2]. In the past, diagnosis was made if three of the following four
      criteria were met: (1) history of cat exposure with inoculation, (2) positive
      skin test: (3) absent laboratory and histopathologic evidence of other diseases,
      and (4) biopsy findings of granulomatous inflammation [3]. Recent identification
      of the causative organism has led to new diagnostic tests, including serum assays
      for B. henselae antibodies [4]. Although response of the disease to antibiotics
      is poor, spontaneous recovery generally occurs within months to years [3].

PMID- 8553963
TI  - MR evaluation of patients with congenital hyposmia or anosmia.
AB  - OBJECTIVE: The purpose of this study was to evaluate patients with reduced or no
      sense of smell since birth for sites of abnormality by MR imaging. MATERIALS AND
      METHODS: Twenty-five patients who reported no olfactory function since birth were
      evaluated by olfactory testing, sinonasal endoscopy, and MR imaging. Surface coil
      and head coil images of the olfactory bulbs, olfactory tracts, subfrontal cortex,
      and temporal lobes in contiguous 3-mm sections were obtained. Two reviewers
      determined unilateral olfactory bulb and tract volumes and temporal lobe volumes
      in two separate sessions. Qualitative grading for olfactory bulb, olfactory
      tract, olfactory sulcus, subfrontal region, hippocampus, and temporal lobe damage
      also was performed. RESULTS: The absence of olfactory bulbs and tracts (68-84%)
      or the presence of hypoplasia (16-32%) was noted in all cases. Eight individuals
      had Kallmann's syndrome (hypogonadotropic hypogonadism with anosmia). Temporal
      and/or frontal lobe volume loss was noted in five individuals and was mild in all
      but one individual. CONCLUSION: Congenital anosmia or hyposmia appears to be an
      olfactory bulb-olfactory tract phenomenon rather than a cerebral process.

PMID- 8553964
TI  - Laryngeal tuberculosis: CT findings.
AB  - OBJECTIVE: The purpose of this study was to evaluate the CT findings of laryngeal
      tuberculosis (TB). SUBJECTS AND METHODS: CT scans, laryngoscopic examinations,
      and chest radiographs of 12 patients (21-63 years old) with histologically (n =
      8) or bacteriologically (n = 4) confirmed laryngeal TB were retrospectively
      reviewed. RESULTS: Bilateral diffuse thickening of the vocal cords and diffuse
      thickening and increased density of the aryepiglottic folds and paralaryngeal
      tissues were present in all patients. Diffuse thickening of the epiglottis was
      observed in seven patients. In four patients, a focal mass was noted in the
      anterior portions of the vocal cords (n = 3) or tip of the epiglottis (n =1).
      Destruction or sclerosis of cartilage was not found. Subglottic extension of the
      lesion was suspected in only one patient. Enlarged cervical lymph nodes were
      found in five patients. On laryngoscopic examinations, swelling of the vocal
      cords (n = 12) or epiglottis (n = 6) was present in all patients and was
      bilateral in nine patients. Vocal cord mobility was impaired in only one patient.
      Radiographic findings consistent with active pulmonary TB were present in all
      patients. CONCLUSION: Although the CT appearances of laryngeal TB are not
      specific, the possibility of laryngeal TB should be raised when bilateral and
      diffuse laryngeal lesions are encountered without destruction of the laryngeal
      architecture in patients with pulmonary TB.

PMID- 8553965
TI  - Thymic uptake of gallium in a patient with unsuspected hyperthyroidism.

PMID- 8553966
TI  - Using the photo CD in academic radiology.
AB  - Photo CD technology has expanded significantly since its introduction a few years
      ago. Because it is not strictly considered interactive multimedia, it has been
      largely overlooked in the medical field, but it has tremendous capabilities for
      image storage, retrieval, and transfer. Images can be used for both educator
      assisted conferences and self teaching. Adding audio technology to the photo CD
      expands the self-teaching concept. The equipment needed is simple and relatively
      inexpensive. The time required to learn how to create photo CDs is short, and
      they can be produced at almost any institution.

PMID- 8553967
TI  - Helical CT of abdominal aortic aneurysm.

PMID- 8553968
TI  - Filter placement in deep venous thrombosis.

PMID- 8553969
TI  - Angiotensin-converting enzyme inhibitor renography.

PMID- 8553970
TI  - Imaging of liver hemangiomas.

PMID- 8553972
TI  - MR diagnosis of a rare adnexal mass: lithokelyphopedion.

PMID- 8553971
TI  - Addison's disease caused by Paracoccidioides brasiliensis: diagnosis by needle
      aspiration biopsy of the adrenal gland.

PMID- 8553973
TI  - Caval system anomaly: MR imaging demonstration.

PMID- 8553974
TI  - Double window for CT display.

PMID- 8553975
TI  - Ligature causing pseudofracture of a cardiac pacemaker lead.

PMID- 8553976
TI  - Viewing mammograms.

PMID- 8553977
TI  - Re: Idiopathic localized dilatation of the ileum.

PMID- 8553978
TI  - Neural tube defects: prenatal screening.

PMID- 8553979
TI  - Hepatic lymphography: another trick for portal vein location during transjugular
      intrahepatic portosystemic shunts.

PMID- 8553980
TI  - Mucinous carcinoma of the liver mimicking cavernous hemangioma on pre- and
      postcontrast MR imaging.

PMID- 8553981
TI  - Health care systems.

PMID- 8553982
TI  - IV high-dose lipiodol.

PMID- 8553983
TI  - Histoplasma prostatic abscess: rare cause in an immunocompromised patient.

PMID- 8553984
TI  - Re: Tesio twin dialysis catheter system.

PMID- 8553985
TI  - Klippel-Trenaunay-Weber syndrome: three-dimensional sonographic imaging.

PMID- 8553986
TI  - Gas bubbles in the hip joint.

PMID- 8553987
TI  - [Prevention in allergy].

PMID- 8553988
TI  - [Prevalence of cosmetic sensitivity among beauticians].
AB  - Cosmetics are a frequent cause of contact dermatitis, not only in females but
      also in males. Men use cosmetics in the form of deodorant, hair dye and
      aftershave lotions. U.S.A men spent more than 6,000,000,000 million dollars in
      cosmetic products. Responsible substances of contact dermatitis are unidentified
      in many occasions, what impedes the estimation of morbidity data. It is
      calculated that 2-4% of dermatological consultations are due to contact
      dermatitis caused by cosmetics. The Spanish industry manufactures each year
      articles valued in several thousands of million pesetas, 14% of which are
      exported. Annual manufacturing is raising between 10 and 11%. The French journal
      Cosmetology (IMS) pointed as an example the fact that in the third trimester of
      1978, the number of sold products was as follows: 87,880 units of cleansing milk;
      128,020 creams; 237,200 tonics; 10,228 lip protectors. The Committee of European
      Unions for Perfumery and Cosmetology (COLIPA) reported in 1978 a yearly sale in
      Europe of 225,000,000 units of hair dyes, exclusively. Adverse reactions to
      cosmetics affect not only the skin in the form of irritant or contact dermatitis,
      but cases of conjunctivitis, asthma, urticaria, rhinitis, angioedema, pneumonitis
      and anaphylaxis-like reactions due to cosmetic products, mainly hair bleaching
      agents, perm liquids and hair spray, have been also reported. The present work
      studied the prevalence of sensitizations to cosmetic products on the professional
      staff of a beauty salon in our city of Las Palmas (SEM). Twenty people came to
      our Unit of Allergology to fill a questionnaire and undergo a skin test.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8553989
TI  - [Multicenter drug surveillance of sublingual immunotherapy in allergic patients].
AB  - A study of pharmacovigilance has been performed in 522 patients suffering from
      allergic rhinitis and/or asthma. Sensitization was due to pollens and mites in
      ther majority of cases. The treatment consisted in biologically standardized
      glycerinated allergenic extracts for specific sublingual immunotherapy (SLIT)
      and, major allergens were also quantified, depending on the allergenic
      composition. The aims of the study were to assay the effect of the SLIT in a
      short-and-medium-term course and to know the adverse reactions most frequently
      appearing, as well as the unexpected side effects that are only possible to know
      through the study of a numerous sample of patients. We also evaluated the factors
      that can modify the tolerance of the treatment, such as the onset of patient's
      disease and its severity. All the patients had a clinical history of, at least,
      two years of evolution and positive skin-prick test to the allergen/s cause of
      their atopic disorder. Exclusion criteria were immunotherapy in the last two
      years, pregnancy and those situations in which the immunotherapy is
      contraindicated according to the EAACI requirements. In order to carry out the
      daily record of the SLIT as well as the possible appearance of symptoms, two
      diaries were given to each patient. Tolerance was evaluated by the physician at
      the end of the build-up phase (3 months) and when the maintenance phase finished
      (5 months later). Total administered doses were 44.021, the final number of
      patients who registered any adverse reaction in relation with SLIT was 41 (7.9%),
      with a number of 67 adverse reactions that means a 0.15% over the total
      administered doses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8553990
TI  - Mast cell quantification in the skin of children with atopic dermatitis: its
      value in diagnosis and in assessing the effectiveness of therapy.
AB  - This study reports on the usefulness of skin mast cell quantification (mast
      cells(mm2) as a parameter for the diagnosis of atopic dermatitis (AD) and for
      determining the efficacy of the therapeutic measures employed. Fifteen children
      with AD of moderate to extreme severity, and which started within the first two
      years of life, were studied. The therapeutic measures were limited to advice
      regarding the choice of adequate living conditions and of an appropriate diet in
      conjunction with the oral administration of hydroxyzine. Before treatment, 11
      children with active AD were submitted to biopsies of both affected and non
      affected skin. After treatment, in six children who were asymptomatic for at
      least one month, another biopsy was performed at a site of previous skin disease.
      A biopsy of a previously affected site was also performed in the other four
      children with a personal history of AD and who had no symptoms for more than one
      year. Treatment with hydroxyzine significantly reduced the number of papillar and
      reticular mast cells/mm3 of affected skin. In children who had been asymptomatic
      for one month, the number of papillar dermis mast cells/mm3 was greater than in
      those who had been asymptomatic for 12 months. In both groups of asymptomatic
      children, the number of mast cells/mm3 of affected skin was greater than in non
      affected skin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8553991
TI  - Aspergillus fumigatus somatic antigens: comparison between two methods of
      preparation and immunochemical characterization.
AB  - Aspergillus fumigatus and other species of the same genus can cause different
      pathological processes amongst which can be found pulmonary hypersensitivity,
      intracavitary colonization and invasive and disseminated aspergillosis. The
      diagnosis of these processes is helped in a great way by the immunological
      response of the patient to Aspergillus antigens or by the detection of these as a
      metabolic product in blood and other fluids such as urine. To date, no firm
      agreement exists regarding the best preparation and standardization technique of
      aspergillar antigens, which is however the most important step towards the
      development of immunological diagnostic tests. In this study, two methods for the
      obtention of A. fumigatus somatic antigens have been compared, using 3 strains of
      different origins. The main differences between both antigenic extraction methods
      were the liquid media used for cultures (Czapek and Glucose peptone), the
      incubation times (4 weeks and 3 days respectively), the type of agitation during
      the incubation period (intermittent or continuous) and the dialysis and
      concentration method. The antigens obtained were standardized by the
      determination of the proteic and hydrocarbonate content, vertical electrophoresis
      in SDS PAGE, immunoprecipitation and immunoblotting against experimental
      antisera. From the comparison between both extraction methods, it was found that
      the highest proteic content was obtained with the somatic antigens of mycelium
      developed in Czapek for 4 weeks, whereas fungi cultivated in Glucose peptone had
      a higher glucide content. Vertical electrophoresis revealed the presence of 6
      common fractions in all the antigens, whilst some fractions were in majority,
      only found in one antigen such as the MW 109 kDa, present in the GP 69
      antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8553992
TI  - Sinusitis and asthma: associations, influences and principles of management.

PMID- 8553993
TI  - Inhaled steroids treatment and withdrawal in asthmatic children.
AB  - Twenty young mild asthmatics (age range 7-22 yrs) were studied in order to
      determine the time course of bronchial hyperresponsiveness during inhaled steroid
      treatment and after steroid withdrawal. Study has been divided in three periods:
      Baseline (two weeks), Treatment (eight weeks) and placebo (eight weeks). Inhaled
      budesonide was administered during treatment period at a doses of 0.4 or 0.6
      mg/ml twice a day, depending on age. After withdrawal, placebo was administered
      in the same way. Bronchial responsiveness (BR) to exercise was estimated trough
      the Bronchial Lability Index (BLI) defined as the amplitude of change of peak
      expiratory flow rate in a percentage related to the basal during a free running
      test. A BLI higher than 20% defined Bronchial Hyperresponsiveness (BHR). All
      patients presented BHR during the baseline period. Forced spirometry and exercise
      tests were performed every two weeks throughout the study. No changes in
      spirometric parameters (FVC, FEV1) were observed either during treatment or
      during placebo periods. A highly significant decrease in BR to exercise was
      observed during active drug treatment (BLI = 32.4 +/- 3.1 to 8.2 +/- 0.7 from
      basal to the end of the two months treatment period, mean +/- sd). During the
      placebo period 10/17 patients increased BLI to near baseline values, and 7/17
      patients remained at normal levels. This behaviour was related to the severity of
      asthma during infancy. Our results confirm the close association between
      inflammation and BHR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8553994
TI  - Impaired fibrinolysis early after percutaneous transluminal coronary angioplasty
      is associated with restenosis.
AB  - This study examined the role of fibrinolytic components in the process of
      restenosis after percutaneous transluminal coronary angioplasty (PTCA). Seventy
      two patients with single-vessel disease who underwent successful PTCA were
      prospectively selected. Tissue plasminogen activator (TPA), free plasminogen
      activator inhibitor-1 (free PAI-1), TPA/PAI-1 complex, and total PAI-1 antigen
      levels were measured before, at 1 week after, and at 3 months after PTCA. Six
      months after PTCA, the study patients were divided into two groups: 41 patients
      without restenosis and 31 patients with restenosis. There were no significant
      differences with regard to sex, age, coronary risk factors, or morphologic
      changes in the target lesions between the two groups. There were no significant
      differences in plasma TPA, TPA/PAI-1 complex, or total PAI-1 levels at each
      sampling period, or in the time courses between the two groups, except for total
      PAI-1 levels at 1 week after PTCA. Although no significant differences in free
      PAI-1 levels before PTCA were observed, free PAI-1 levels after PTCA in the
      patients with restenosis were significantly higher than those in the patients
      without restenosis. In addition, each group had a significant change in the time
      course of free PAI-1 levels. The results suggest that impaired fibrinolysis early
      after PTCA might affect the repair process of vascular injury, which leads to
      restenosis, and also that serial determination of free PAI-1 levels could help
      predict restenosis.

PMID- 8553995
TI  - Transesophageal Doppler echocardiographic assessment of left coronary blood flow
      velocity in chronic aortic regurgitation.
AB  - Assessment of systolic and diastolic coronary blood flow velocities (FVs) in
      patients with aortic regurgitation (AR) has remained a clinical challenge. We
      recorded left anterior descending coronary blood FV in 21 patients with chronic
      AR an in 6 control subjects using transesophageal pulsed Doppler
      echocardiography. In 7 patients FV was measured 4.0 +/- 5.2 months after aortic
      valve replacement. Peak and mean FVs during systole and diastole and
      systolic/diastolic ratios of these FVs were determined. Left ventricular (LV)
      mass index was calculated by means of standard M-mode echocardiography. In
      patients with severe AR, peak and mean systolic FVs were significantly increased
      (34 +/- 8 cm/sec and 21 +/- 6 cm/sec, respectively) compared with FVs in the
      control group (15 +/- 4 and 12 +/- 3 cm/sec, respectively) and in patients with
      mild AR (17 +/- 3 cm/sec and 13 +/- 2 cm/sec, respectively). Peak and mean
      systolic FVs were also significantly increased in severe AR (54 +/- 13 cm/sec and
      33 +/- 9 cm/sec, respectively) compared with FVs in the control (30 +/- 8 cm/sec
      and 21 +/- 5 cm/sec, respectively) and mild AR groups (30 +/- 5 cm/sec and 21 +/-
      4 cm/sec, respectively). Peak systolic and diastolic FVs were correlated
      significantly with LV mass index (r = 0.72 and r = 0.73, respectively). Systolic
      and diastolic FVs and LV mass index were significantly decreased, normalized or
      both after aortic valve surgery. In conclusion, LV mass seems to have an effect
      on the significantly increased systolic and diastolic left coronary blood FV
      pattern in patients with chronic, severe AR. Increased systolic and diastolic FV
      appears to be normalized in the late period after surgery.

PMID- 8553996
TI  - Cardioscopic spectrum of the left ventricular endocardial surface and its
      relation to histologic changes in idiopathic myocarditis.
AB  - To examine feasibility of percutaneous cardioscopy for diagnosis of idiopathic
      myocarditis, cardioscopic appearance of the left ventricle and biopsy findings
      were compared in 21 such patients. The endocardial surface was milky white, red,
      pink, or reddish brown and edematous at the segments that exhibited histologic
      changes of acute myocarditis; purplish red in those that exhibited chronic active
      myocarditis; and yellow in those that exhibited chronic inactive or healed
      myocarditis. Follow-up study by repeated cardioscopy and biopsy in six patients
      revealed that the milky white surface disappeared and that the red, pink, and
      reddish brown surfaces changed to purplish red and then to yellow or white. The
      results indicate that the endocardial coloration of the left ventricle represents
      histologic changes and that cardioscopy is feasible for macroscopic pathologic
      diagnosis and for follow-up of idiopathic myocarditis.

PMID- 8553997
TI  - Ultrasonic myocardial tissue characterization in patients with dilated
      cardiomyopathy: value in noninvasive assessment of myocardial fibrosis.
AB  - Dilated cardiomyopathy (DCM) is usually diagnosed from the left ventricular
      functional viewpoint by the detection of dilated ventricular cavity and depressed
      myocardial contractility. Although histologic analysis of the myocardium no doubt
      provides clinically important information, it is possible only with microscopic
      examination of biopsy specimen of the myocardium. The objective of this
      particular study is to clarify the comparative values of the measures of
      ultrasonic tissue characterization, that is, calibrated myocardial integrated
      backscatter (IB) and the magnitude of cyclic variation in IB, with conventional
      echocardiographic parameters in assessing histologic condition of the myocardium.
      The magnitude of cyclic variation in IB and myocardial IB at end-diastole
      calibrate with the power of Doppler signals from the blood were measured in
      addition to conventional echocardiographic parameters in 14 patients with DCM.
      Calibrated myocardial IB was higher in patients with more fibrosis in the biopsy
      specimen of the heart tissue, whereas the magnitude of variation in IB or
      conventional echocardiographic parameters did not significantly correlate with a
      histologic estimate of myocardial fibrosis. Calibrated myocardial IB provides
      information about the myocardial fibrosis that cannot be assessable with
      conventional echocardiographic parameters. Calibrated myocardial IB and the
      magnitude of cyclic variation of IB are likely to reflect somewhat different
      acoustic properties of the myocardium.

PMID- 8553998
TI  - Influence of left atrial function on Doppler transmitral and pulmonary venous
      flow patterns in dilated and hypertrophic cardiomyopathy: evaluation of left
      atrial appendage function by transesophageal echocardiography.
AB  - Information regarding the relation of left atrial (LA) function to transmitral
      and pulmonary venous (PV) flow is limited. Using transesophageal
      echocardiography, we analyzed this relation in 23 patients with dilated
      cardiomyopathy (DCM) and 25 patients with hypertrophic cardiomyopathy (HCM). Left
      atrial appendage (LAA) function was assessed as a substitute for overall LA
      function. Transmitral and PV flow-velocity variables, the LAA emptying flow
      velocity (LAA-A), and the LAA ejection fraction (LAA-EF) were determined. Each
      patient group was divided into two subgroups with a normal ( < 15 mm Hg) or
      elevated ( > or = 15 mm Hg) mean pulmonary wedge pressure (PWP). Transmitral and
      PV flow patterns as well as LA function were similar in the two subgroups with a
      normal PWP (11 patients with DCM and 14 patients with HCM). For the subgroups
      with an elevated PWP, however, the peak velocity ratio of the early filling wave
      (E) to atrial contraction wave (A) was higher in DCM patients (n = 12) than in
      HCM patients (n = 11) (2.1 +/- 0.7 vs 1.3 +/- 0.2; p < 0.01). This difference
      mostly resulted from a lower A velocity in the DCM group than in the HCM group
      (30 +/- 10 cm/sec vs 43 +/- 7 cm/sec; p < 0.05). In addition, the reverse flow
      velocity at atrial contraction in the PV was lower in the DCM group than in the
      HCM group (19 +/- 8 cm/sec vs 37 +/- 8 cm/sec; p < 0.01). These findings were
      associated with poorer LA systolic function in the DCM group (LAA-A, 35 +/- 13
      cm/sec vs 60 +/- 11 cm/sec; LAA-EF, 37% +/- 12% vs 55% +/- 15%, p < 0.05,
      respectively). Our data suggest that a restrictive transmitral flow pattern
      develops more easily in DCM than in HCM because LA dysfunction is present in DCM,
      and that LA contractility plays an important role in determining the atrial
      contraction wave of transmitral and PV flows with elevated LA pressure.

PMID- 8553999
TI  - Differential responses in left ventricular diastolic filling dynamics with
      isometric handgrip versus isotonic treadmill exertion.
AB  - Although the hemodynamic responses to isotonic and isometric exercise are
      different, few data exist comparing the response to left ventricular (LV)
      diastolic filling dynamics with these two forms of exertion. Therefore we
      performed Doppler examination before and at the end of isotonic and isometric
      exercise in 20 normal volunteers to define the differential responses of LV
      filling to these two forms of exertion. Transmitral inflow velocity signals from
      the apical view and phonocardiography were recorded before and at the termination
      of treadmill exercise (TRD) to 11 METs and handgrip (HG) 50% maximal for 2
      minutes). Mean blood pressure (mBP), heart rate (HR), early diastolic (E) and
      late atrial (A) inflow velocities, mean acceleration rate (ACC) of E wave, time
      velocity integral of inflow (Ti), and isovolumic relaxation time (IRT) from
      second heart sound to onset mitral inflow were measured. Absolute changes from
      baseline were significantly different for the two forms of exertion: TRD versus
      HG: BP = 11 +/- 9 versus 36 +/- 10 mm Hg, HR = 37 +/- 16 versus 16 +/- 9
      beats/min, E = 11.6 +/- 11.3 versus -7.0 +/- 9.4 cm/sec, A = 29.9 +/- 14.5 versus
      14 +/- 12 cm/sec, ACC = 164 +/- 151 versus -56 +/- 135 cm/sec2, Ti = 1.9 +/- 3.0
      versus -1.7 +/- 1.7 cm, and IRT = -12 +/- 9 versus 9 +/- 10 msec, all p < 0.0001
      except for A, p < 0.001). Isotonic treadmill exercise resulted in enhanced early
      diastolic filling manifested by increases in E and ACC and a decreased in IRT.
      Conversely, isometric handgrip exercise produced evidence of reduced early
      filling including decreased E and ACC and slightly increased IRT. Thus the
      response of LV filling dynamics recorded by Doppler differs for isotonic and
      isometric exertion and likely reflects the variable pressure and flow alterations
      induced by these two forms of exertion.

PMID- 8554000
TI  - Systolic excursion of the mitral annulus to assess septal function in paradoxic
      septal motion.
AB  - To determine whether mitral valve annulus displacement (MVAD) can be used to
      assess septal contractility in patients with paradoxical septal motion, we
      assessed four atrioventricular regions (septum, lateral wall, anterior wall, and
      inferior wall) by MVAD in 80 consecutive patients. The patients were divided into
      five groups: group 1 (control) (n = 20), normal left ventricular (LV) systolic
      function; group 2 (n = 15), paradoxical septal motion resulting from left bundle
      branch block (LBBB) and normal segmental and global LV systolic function; group 3
      (n = 19), paradoxical septal motion as a result of cardiac surgery, and normal
      segmental and global LV systolic function; group 4 (n = 11), paradoxical septal
      motion resulting from LBBB, dilated cardiomyopathy, and severely depressed LV
      systolic function; group 5 (n = 15), septal hypokinesis with either normal or
      mildly depressed global LV systolic function. In groups 1, 2, and 3, 80% to 100%
      of patients had septal and other regional MVAD > or = 1.0 cm. The average MVAD in
      group 4 (dilated cardiomyopathy), was significantly decreased ( < or = 0.8 cm) in
      all four regions (p < 0.01 compared with groups 1, 2, and 3). In group 5 (septal
      hypokinesis), the septal MVAD was > or = 1.0 cm in only 13% of the patients (p <
      0.025 compared with groups 1, 2, and 3). In conclusion, patients with paradoxical
      septal motion caused by LBBB or cardiac surgery have preserved septal
      contractility when evaluated by MVAD.

PMID- 8554001
TI  - Verapamil reduces the size of reperfused ischemically injured myocardium in
      hypertrophied rat hearts as assessed by magnetic resonance imaging.
AB  - Contrast-enhanced magnetic resonance (MR) imaging was used to detect and quantify
      the extent of myocardial injury after a brief coronary occlusion and reperfusion
      in response to verapamil treatment in a rat model of left ventricular hypertrophy
      (LVH). Two groups of rats were prepared by banding the abdominal aorta for 7 to 8
      weeks to produce LVH. Group 1 (n = 13) received oral verapamil for 3 days,
      whereas group 2 (n = 13) received no therapy. Before MR examination was
      performed, each rat was subjected to 25 min of coronary artery occlusion followed
      by 1 hour of reperfusion. T1-weighted spin echo images were acquired before and
      after 0.3 mmol/kg gadoteridol was injected. Three images were acquired at
      contiguous levels of the LV and used to estimate the size of the myocardial
      injury. The size of the infarcted region was demarcated at postmortem examination
      by using triphenyltetrazolium chloride dye (TTC). Before contrast medium was
      administered, no significant difference in signal intensity was seen between
      nonischemic and reperfused ischemically injured myocardium. After gadoteridol was
      injected, a hyperintense zone indicative of myocardial injury was observed in 8
      of 13 rats treated with verapamil and in all untreated animals. The size of the
      injury was significantly larger in untreated hearts than in hearts treated with
      verapamil as defined on MR images (25% +/- 5% vs 18% +/- 5%, p < 0.05) and TTC
      staining (12% +/- 4% and 4% +/- 1%, p < 0.05). Good correlation (r = 0.91) was
      found between the two measurements. No significant difference in the size of
      jeopardy area was seen between the two groups as (defined by blue dye infusion).
      In conclusion, contrast-enhanced MR imaging is a suitable technique to evaluate
      the effects of therapies applied to reduce myocardial injury. Verapamil can cause
      reduction in the extent of ischemic injury after reperfusion of hypertrophied
      myocardium.

PMID- 8554002
TI  - Increased malondialdehyde in peripheral blood of patients with congestive heart
      failure.
AB  - Malondialdehyde (MDA), a marker of lipid peroxidation, was measured in the plasma
      of patients with congestive heart failure (CHF) having varying degrees of
      clinical symptoms and in control subjects. The 53 patients studied were divided
      in two groups based on their left ventricular ejection fraction (LVEF). Group A
      consisted of 30 symptomatic patients with chronic CHF (NYHA classes II and III)
      and LVEF < 40%. Group B consisted of 23 asymptomatic patients with LVEF > 40%.
      Patients in group A (mean LVEF = 28) has a significantly greater history of
      myocardial infarction (88% vs 48%; p = 0.002) than those in group B. Group B
      patients and the controls had similar LVEFs (58.0 vs 62.1; p = 0.14). Neither
      patients in the CHF group nor group B patients showed correlation between MDA
      values and LVEF, unless control were included. Mean MDA concentrations in groups
      A (2.65 +/- 1.03 mumol/L) and B (2.1 +/- 0.7 mumol/L) were significantly higher
      than those in the control group (1.45 +/- 0.77 mumol/L; p < 0.05), supporting the
      hypothesis that the CHF state and underlying risk conditions appear to be
      associate with abnormal oxidative stress. Moreover, a significant correlation (r
      = 0.74; p = 0.0001) was found in group A patients between the MDA values and the
      duration in years (chronicity) of the CHF state.

PMID- 8554003
TI  - Role of spectral measures of heart rate variability as markers of disease
      progression in patients with chronic congestive heart failure not treated with
      angiotensin-converting enzyme inhibitors.
AB  - Measures of heart rate variability in the frequency domain quantify autonomic
      activity. However, the relation of these measures to the severity of ventricular
      dysfunction in patients with congestive heart failure remains uncertain. We
      applied spectral analysis of heart rate variability to 24-hour Holter monitor
      recordings obtained from 20 patients with congestive heart failure who were not
      treated with angiotensin-converting enzyme inhibitors to determine whether
      significant changes in parameters of heart rate variability reflect the
      progression of symptoms in patients with ventricular failure. Both total and low
      frequency heart rate spectral power were seen to decrease with worsening New
      Heart Associate (NYHA) functional class. A significant (p = 0.04) higher total
      power was noted in NYHA class II than in class III patients (3.0 x 10(-3) +/- 3.6
      10(-4) and 2.5 x 10(-3) +/- 5.9 x 19(-4) [beats/min]2, respectively). Similarly,
      low-frequency heart rate spectral power was significantly (p = 0.008) higher in
      class II than in class III patients (1.7 x 10(-3) +/- 4.6 x 10(-4) and 1.1 x 10(
      3) +/- 3.5 x 10(-4) [beats/min]2, respectively). Only the low-frequency component
      of the spectrum was directly correlated with left ventricular ejection fraction
      (LVEF) (r = 0.40) with a trend toward statistical significance (p = 0.07).
      Measures of heart rate variability and the changes in autonomic tone that they
      reflect may therefore serve as markers of the extent of disease progression in
      patients with congestive heart failure.

PMID- 8554004
TI  - Patent foramen ovale: association between the degree of shunt by contrast
      transesophageal echocardiography and the risk of future ischemic neurologic
      events.
AB  - This study investigated whether there is an association between the degree of
      interatrial shunting across a patent foramen ovale, as determined by saline
      contrast transesophageal echocardiography, and the risk of subsequent systemic
      embolic events, including stroke. Thirty-four patients found to have foramen
      ovale during transesophageal echocardiography were divided into two groups on the
      basis of the maximum number of microbubbles in the left heart in any single frame
      after intravenous saline contrast injection: group 1 (n = 16) with a "large"
      degree of shunt ( > or = 20 microbubbles) and group 2 (n = 18) with a "small"
      degree of shunt ( > or = 3 microbubbles). Patients were followed up over a mean
      period of 21 months for subsequent systemic embolic events, including transient
      ischemic attack and stroke. Five (31%) of the patients with large shunts had
      subsequent ischemic neurologic events, whereas none of the patients with small
      shunts had embolic events (p = 0.03). These events occurred in spite of
      antiplatelet or anticoagulant therapy. We conclude that patients with a large
      degree of shunt across a patient foramen ovale, as determined by contrast
      transesophageal echocardiography, are at a significantly higher risk of
      subsequent adverse neurologic events compared with patients with a small degree
      of shunt.

PMID- 8554005
TI  - Role of echocardiography in perioperative management of patients undergoing open
      heart surgery.
AB  - TEE has assumed a pivotal role in the perioperative management of patients
      undergoing open-heart surgery. The information obtained influences important
      therapeutic decisions in thoracic aortic surgery, valvular surgery, and coronary
      artery bypass surgery. TEE also assists in determining the reason for failure to
      wean from cardiopulmonary bypass and allows rapid detection of the etiology of
      hypotension in the patient after surgery. Advances in technology have resulted in
      three-dimensional images of cardiac structures, and this will further enhance the
      usefulness of echocardiography for the surgeon. TEE should no longer be regarded
      as an imaging tool available only in academic centers, but should be routinely
      used by qualified operators in centers performing open-heart surgery.

PMID- 8554006
TI  - Direct selective blockade of the vascular angiotensin II receptors in therapy for
      hypertension and severe congestive heart failure.
AB  - ACEIs are widely prescribed antihypertensives and have become the mainstay of
      therapy for severe CHF. Nevertheless, a focused AII-receptor blockade has
      compelling intellectual appeal and substantial clinical advantages over the ACEIs
      (no disruption of the prostaglandin and bradykinin biosystems). Identification
      and careful characterization of the AII receptors and the recent discovery of
      their antagonists has led to the extensive clinical investigation of selective
      AII-receptor blockers in both hypertension and severe CHF. Studies with the first
      orally active AII-receptor blocker, losartan, have demonstrated safe and
      effective control of elevated blood pressure and improvement of the abnormal
      hemodynamics typical of pronounced CHF. Several other oral AII-receptor blockers
      are currently being evaluated, and early results with these agents are
      encouraging.

PMID- 8554007
TI  - Clinical spectrum, therapeutic management, and follow-up of ventricular
      tachycardia in infants and young children.
AB  - We reviewed 40 infants and young children with VT. Median maximum VT rate was 214
      beats/min (range 152 to 375 beats/min). A cause was defined in 20 (50%), the most
      common being cardiomyopathy or myocarditis in 8 (20%). There were six deaths
      (15%) related to VT, three of which occurred at diagnosis and in patients less
      than 1 week old. In 5 of 6 deaths related to VT, a cause was defined. At follow
      up, 31 (91%) of 34 survivors did not have VT. The presence of symptoms was a
      predictor of death related to VT. The outlook for asymptomatic patients and those
      who survived more than 6 months after diagnosis and who do not have progressive
      myocardial disease appears good.

PMID- 8554008
TI  - A word of caution on optimizing stent deployment in calcified lesions: acute
      coronary rupture with cardiac tamponade.

PMID- 8554009
TI  - Multiple coronary thromboemboli complicating valvular heart disease and atrial
      fibrillation.

PMID- 8554010
TI  - Angiographic presence of myocardial bridge after successful percutaneous
      transluminal coronary angioplasty.

PMID- 8554011
TI  - Cardiac tamponade without pericardial effusion after blunt chest trauma.

PMID- 8554012
TI  - Pseudocoarctation of the aorta complicated by saccular aneurysm: treatment by
      aortic arch replacement.

PMID- 8554013
TI  - Association of metoprolol and retroperitoneal fibrosis.

PMID- 8554014
TI  - Heart rate reduction in the treatment of chronic stable angina pectoris:
      experiences with a sinus node inhibitor.

PMID- 8554015
TI  - MB fraction of cumulative creatine kinase correlates with insulin secretion in
      patients with acute myocardial infarction: insulin as a possible determinant of
      myocardial MB creatine kinase.
AB  - To test whether insulin is a regulatory factor of myocardial MB creatine kinase
      content, we investigated the correlation between the ability of insulin secretion
      and the MB fraction of cumulative CK released in patients with acute myocardial
      infarction. We analyzed 18 patients who underwent successful direct angioplasty
      within 10 hours of the onset of their first myocardial infarction. Exclusion
      criteria were age more than 75 years, heart failure, severe obesity, multivessel
      disease, and history of diabetes mellitus. Cumulative activity of serum MB CK
      divided by that of total CK was defined as MB%, which was considered to represent
      myocardial MB CK content. Two weeks or more after the onset of myocardial
      infarction, 75 gm oral glucose tolerance test with serial determination of plasma
      glucose and serum insulin (0, 0.5, 1, 2, 3 hours) was done. Urinary and plasma
      catecholamines and echocardiographic left ventricular (LV) mass were measured.
      MB% significantly correlated with insulinogenic index (r = 0.564, p = 0.019),
      insulin area (r = 0.594, p = 0.012), insulin area/glucose area (r = 0.630, p =
      0.007), and urinary adrenaline (r = -0.542, p = 0.025) and tended to correlate
      with plasma adrenaline (r = -0.431, p = 0.084). Age, body mass index, infarct
      size, glucose metabolism, and LV mass were not significant univariate predictors
      of MB%. Multivariate analysis showed that the ability of insulin secretion
      contributed to MB% more than catecholamines did and that insulin area/glucose
      area was the strongest independent predictor of MB% (t = 3.01, p = 0.015). Thus
      MB fraction of cumulative CK released, indicative of Myocardial MB CK
      distribution, strongly related to the ability of insulin secretion in subjects
      without overt insulin resistance. Regulation by insulin of myocardial MB CK is
      suggested.

PMID- 8554016
TI  - Correlation of regional wall motion abnormalities detected by two-dimensional
      echocardiography with perfusion defect determined by technetium 99m sestamibi
      imaging in patients treated with reperfusion therapy during acute myocardial
      infarction.
AB  - Twenty patients (13 men and 7 women; mean age 61 +/- 12 years) with > 30 minutes
      chest pain and new ST-segment elevation who were treated with reperfusion therapy
      underwent technetium 99m sestamibi imaging and two-dimensional echocardiography
      simultaneously before and within 2 hours of each test after acute reperfusion
      therapy. Nine patients had anterior wall myocardial infarction. Fifteen patients
      were initially treated with intravenous thrombolytic agents, and five patients
      underwent urgent percutaneous transluminal coronary angioplasty. Both myocardial
      perfusion defect and wall motion score index (WMSI) improved after reperfusion
      therapy (perfusion defect from 28% to 15%, WMSI from 1.68 to 1.45, respectively;
      p < 0.005). The overall correlation between WMSI and perfusion defect as a
      measure of myocardium at risk was significant during the acute phase (r = 0.71)
      and at hospital dismissal (r = 0.71). Thus myocardial perfusion defect and wall
      motion abnormalities correlated fairly well in patients with acute myocardial
      infarction during the acute phase and at predismissal study.

PMID- 8554017
TI  - Acute myocardial infarction entailing ST-segment elevation in lead aVL:
      electrocardiographic differentiation among occlusion of the left anterior
      descending, first diagonal, and first obtuse marginal coronary arteries.
AB  - Acute myocardial infarction with ST elevation in lead aVL may represent
      involvement of the first diagonal or the first obtuse marginal branch. This study
      assesses the correlation among different electrocardiographic patterns of acute
      myocardial infarction with ST elevation in aVL and the site of the infarct
      related artery occlusion. Patients who underwent coronary angiography within 14
      days of infarction with an unequivocal culprit lesion were included. Fifty-seven
      patients were evaluated. The culprit lesion was in the left anterior descending
      coronary artery proximal to the first diagonal, first diagonal, and first obtuse
      marginal branches, in 38, 8, and 11 patients, respectively. ST elevation in aVL
      and V2 through V5 signifies left anterior descending artery occlusion proximal to
      the first diagonal branch (positive predictive value [PPV] and negative
      predictive value [NPV] of 95% and 94%, respectively). ST elevation in aVL and V2,
      not accompanied by ST elevation in V3 through V5, favors occlusion of the first
      diagonal branch (PPV, 89%; NPV, 100%). ST elevation in aVL accompanied by ST
      depression in V2 predicts obstruction of the first obtuse marginal branch (PPV,
      100%; NPV, 98%).

PMID- 8554018
TI  - Gender differences and factors associated with the receipt of thrombolytic
      therapy in patients with acute myocardial infarction: a community-wide
      perspective.
AB  - In spite of national interest in gender differences in the presentation and
      management of chronic disease, limited information is available about possible
      gender differences in the receipt of thrombolytic therapy after acute myocardial
      infarction (AMI). As part of an ongoing community-based study of AMI, we examined
      gender differences in the receipt of thrombolytic therapy among 2885 patients
      with confirmed AMI. The study sample consisted of 1680 males and 1205 females
      with validated AMI who were admitted to 16 hospitals in the Worcester,
      Massachusetts, metropolitan area in four study periods between 1986 and 1991.
      During the years under study, 24.4% of men and 14.4% of women received
      thrombolytic therapy. Increases over time in the use of thrombolytic therapy were
      seen in both men (13.9% in 1986; 31.6% in 1991) and women (3.2% in 1986; and
      19.0% in 1991). After controlling for a variety of factors that might affect use
      of thrombolytic agents, younger age, absence of a history of either congestive
      heart failure or stroke, and experiencing a Q-wave AMI were associated with
      receipt of thrombolytic therapy in both men and women; having an anterior AMI
      also was associated with use of thrombolytic agents in men. Women without as
      compared with those with a history of angina pectoris were significantly more
      likely to receive thrombolytics. Men who had Medicare insurance were
      significantly less likely to receive thrombolytics than were men with other types
      of health insurance. When this analysis was restricted to patients who were seen
      in area-wide hospitals within 6 hours of the onset of symptoms suggestive of AMI,
      similar factors were associated with the receipt of thrombolytic agents in men
      and women. The results of this community-wide study suggest a marked increase
      over the 5-year study period in the use of thrombolytic therapy in both men and
      women, with a greater relative increase observed in women. A relatively similar
      profile of patients likely to receive thrombolytic therapy was seen in both men
      and women.

PMID- 8554019
TI  - Clinical assessment of adrenergic tone and responsiveness to beta-blocker therapy
      in patients with symptomatic ventricular tachycardia and no apparent structural
      heart disease.
AB  - To further define the relation between changing adrenergic tone, beta-blocker
      therapy, and clinical ventricular tachycardia (VT), we evaluated these factors in
      35 patients with VT unrelated to coronary artery disease or ventricular
      dysfunction. Testing included Holter monitoring (91% had VT), exercise test (69%
      had VT), Adrenergic responsiveness of VT was graded according to diurnal
      variation, response to exercise, isoproterenol infusion, and response to beta
      blockers. beta-Blockers were effective and well tolerated in this population.
      There was also a predictable relation between changing adrenergic tone and the
      arrhythmia response to beta-blocker therapy.

PMID- 8554020
TI  - Implantable cardioverter defibrillator: use in patients with no symptoms and at
      high risk.
AB  - Twenty-seven patients with asymptomatic, nonsustained ventricular tachycardia
      whose evaluation suggested they were at high risk for sustained ventricular
      arrhythmias were treated with implantable cardioverter defibrillators. The option
      of conventional therapy (including the option of no therapy) was presented to
      each patient and rejected in favor of defibrillator implantation on an
      experimental basis. Eighteen patients had coronary artery disease and inducible
      sustained ventricular tachycardia, 8 had idiopathic dilated cardiomyopathy, and 1
      had hypertrophic cardiomyopathy and a strong family history of sudden cardiac
      death. The mean ejection fraction was 27% +/- 10%. Operative morbidity (3%) and
      mortality (3%) were low. Mean overall survival was 92% and 88% at 1 and 2 years,
      respectively. Sixteen (59%) of the 27 patients had appropriate defibrillator
      discharges during a mean follow-up of 35 +/- 15 months. The mean time to first
      appropriate discharge was 18 +/- 17 months, and mean follow-up after first
      discharge was 17 +/- 20 months. In conclusion, implantable cardioverter
      defibrillator placement in high-risk patients without symptoms is a feasible
      approach that may have resulted in benefit in selected patients. Large-scale
      randomized trials currently under way will determine the risk/benefit ratio of
      this management approach.

PMID- 8554021
TI  - Efficacy and risks of medical therapy for supraventricular tachycardia in
      neonates and infants.
AB  - To assess the efficacy and safety of current pharmacologic therapy for
      supraventricular tachycardia (SVT) in infants, we reviewed 112 infants treated
      between July 1985 and March 1993. The SVT mechanism was determined by esophageal
      electrophysiologic study and involved an accessory pathway in 86,
      atrioventricular (AV) node reentry in 10, atrial muscle reentry in 11, and an
      ectopic atrial tachycardia in 5 patients. Of six infants not treated, none had
      clinical recurrences of SVT. Of the 106 patients treated, 70% remained free of
      tachycardia while receiving digoxin, propranolol, or both. Class I antiarrhythmic
      agents were necessary for 13 patients, and class III agents were required for
      another 13 infants. Verapamil was used in one infant with AV node reentry
      tachycardia. Nine infants with complex clinical presentations were believed to
      have failed medical management and underwent radiofrequency ablation. Five
      patients died, four of complications related to structural heart disease and one
      shortly after radiofrequency ablation was performed. No deaths appeared to be
      related to antiarrhythmic medications. No drug-related side effects requiring
      medication change occurred, and no proarrhythmia was observed. Thus medical
      therapy appears to be effective and safe in infants with SVT. Radiofrequency
      ablation should be reserved for rare infants who fail aggressive medical regimens
      or when the situation is complicated by ventricular dysfunction, severe symptoms,
      or complex congenital heart disease.

PMID- 8554022
TI  - Changes in interstitial collagen metabolism during acute myocardial infarction
      treated with streptokinase or tissue plasminogen activator.
AB  - Collagen plays a specific role in the maintenance of vascular integrity and in
      the thrombosis and scar formation processes. Therefore we found it interesting to
      study the changes in interstitial collagen metabolism during acute myocardial
      infarction treated with thrombolytic agents. Changes in collagen synthesis were
      evaluated by obtaining assays of the serum concentrations of the carboxyterminal
      propeptide of type I procollagen. Except fibrin plasmin is capable of degrading
      extracellular matrix components including collagen, and this capability was
      evaluated by monitoring the serum concentrations of the aminoterminal propeptide
      of type III procollagen. Twenty-four patients with suspected acute myocardial
      infarction and indications for thrombolytic therapy were randomized to receive
      either streptokinase (n = 11) or tissue plasminogen activator (n = 13). The
      patient groups were identical in their clinical characteristics. Serum levels of
      the aminoterminal propeptide of type III collagen increased rapidly on infusion
      of the thrombolytic agents, with the maximal mean increases of 44% and 16% in the
      streptokinase and TPA-treated groups, respectively. Levels of the carboxyterminal
      propeptide of type I collagen did not change during the thrombolytic therapy. A
      transient decrease occurred in the type I propeptide concentration at
      postinfarction day 2, and this decrease was followed by a secondary increase at
      days 4 to 6 in both patient groups studied. We conclude that thrombolytic agents
      stimulate the breakdown of interstitial collagen and that the collagen-degrading
      activity of TPA is lower than that of streptokinase. This factor may contribute
      to the relatively higher rethrombosis rate seen after TPA, because exposed
      collagen in the affected vascular wall stimulates thrombosis formation. On the
      other hand, increased collagen degradation followed by inhibition of collagen
      synthesis in the infarcted myocardium might increase the risk for cardiac
      rupture, especially after streptokinase treatment.

PMID- 8554023
TI  - Changes in left ventricular volume during head-up tilt in patients with vasovagal
      syncope: an echocardiographic study.
AB  - We tested the hypothesis that patients who have vasovagal syncope during head-up
      tilt have a greater decrease in their left ventricular volume in response to tilt
      than do normal subjects. Measurements were done in the supine position and during
      graded tilt by using two-dimensional echocardiography. We compared seven patients
      with vasovagal syncope with nine normal volunteers. The rate of reduction of end
      diastolic volume index during tilt was faster in the vasovagal group than in
      normal subjects. A more significant reduction of stroke index and ejection
      fraction during tilt was found in the vasovagal group than in normal subjects,
      possibly because of more peripheral translocation of blood volume in the venous
      system during tilt and an early vagal effect on ventricular contraction.

PMID- 8554024
TI  - Parental hypertension and cardiac alterations in normotensive children and
      adolescents.
AB  - The objective of this investigation was the examination of the relation of left
      ventricular mass (LVM) and function with cardiovascular response to exercise in
      normotensive adolescents at risk for hypertension. Carried out was a prospective,
      cross-sectional study of 47 subjects (age, 10 to 18 years), who underwent dynamic
      and isometric exercise, 24-hour Holter monitoring, and echocardiography. Twenty
      nine had normotensive parents (group 2, "at risk"). Both groups were similar for
      age, race, sex, body mass index, blood pressures, and resting heart rates. Group
      2 had a higher E/A ratio (2.3 +/- 0.5 vs 2.0 +/- 0.5; p = 0.039) and higher heart
      rates during stage IV of dynamic exercise (188 +/- 20 beats/min vs 176 +/- 18
      beats/min; p = 0.046). The LVM, 24-hour heart rates, and exercise systolic blood
      pressures (SBP) were similar in both groups. Only in group 2, SBP at peak dynamic
      and isometric exercise correlated best with LVM (r = 0.74, p < 0.002; r = 0.82, p
      < 0.001). It is concluded that altered hemodynamic regulatory mechanisms may
      exist before the establishment of hypertension in normotensive subjects with
      parental hypertension.

PMID- 8554025
TI  - Immediate and long-term effect of mitral balloon valvotomy on severe pulmonary
      hypertension in patients with mitral stenosis.
AB  - The pulmonary vascular hemodynamics were studied in 21 patients with severe
      mitral stenosis and severe pulmonary hypertension. Hemodynamic data were obtained
      before and immediately after mitral balloon valvotomy (MBV) and at follow-up 7 to
      14 months (mean 12 months) later by repeat catheterization. The mean pulmonary
      capillary wedge pressure (PCW) decreased from 27 +/- 5 to 15 +/- 4 mm Hg (p <
      0.001). The mean mitral valve gradient (MVG) decreased from 18 +/- 4 to 6 +/- 2
      mm Hg (p < 0.001). Mitral valve area (MVA) increased from 0.6 +/- 0.1 to 1.5 +/-
      0.3 cm2 (p < 0.02). Cardiac index increased from 2.2 +/- 0.3 to 2.6 to 0.5
      L/min/m2 (p < 0.02). The pulmonary artery systolic pressure decreased from 65 +/-
      13 to 50 +/- 13 mm Hg (p < 0.001), and no significant change was seen in
      pulmonary vascular resistance (PVR) immediately after MBV from 461 +/- 149 to 401
      +/- 227 dynes/sec/cm(-5) (p = 0.02). At follow-up the MVA increased from 1.5 +/-
      0.3 to 1.7 +/- 0.3 cm2 (p < 0.02). Cardiac index increased further to 3 +/- 0.4
      L/min/m2 (p < 0.02). MVG and PCW pressure remained the same. The pulmonary artery
      systolic pressure decreased further to 38 +/- 9 mm Hg (p < 0.02). PVR decreased
      significantly to 212 +/- 99 dynes/sec/cm(-5) (p < 0.02). We concluded that the
      pulmonary artery pressure decreased without normalizing immediately after MBV and
      normalized in patients with optimal results from mitral balloon valvotomy 7 to 14
      months later. Insignificant change in PVR was seen immediately after MBV and
      markedly decreased or normalized at late follow-up in patients with optimal
      result from MBV.

PMID- 8554026
TI  - Gender differences in left ventricular function at rest and with exercise in
      asymptomatic aortic stenosis.
AB  - In 29 women and 53 men with asymptomatic aortic stenosis, two-dimensional (2-D)
      and Doppler echocardiography were performed at rest and immediately after
      treadmill exercise testing to examine gender differences in left ventricular
      geometry, systolic and diastolic function, functional status, and exercise
      capacity. Aortic stenosis severity was similar between men and women. Women
      reported more functional impairment than men (88% +/- 14% vs 95% +/- 7%; p =
      0.02). When indexed to body surface area, women had a smaller end-diastolic
      volume (39 +/- 14 vs 50 +/- 15 ml/m2; p = 0.002), end-systolic volume (13 +/- 6
      ml/m2 vs 18 +/- 9 ml/m2; p = 0.01) and left ventricular mass (73 +/- 26 gm/m2 vs
      84 +/- 21 gm/m2; p = 0.05), but a higher relative wall thickness in systole (1.5
      +/- 0.4 cm vs 1.3 +/- 0.4 cm; p = 0.05), and fractional shortening (43% +/- 7% vs
      39% +/- 10%; p = 0.03). Women had higher early and late transmitral velocities
      than did men (early, 92 +/- 24 cm/sec vs 79 +/- 29 cm/sec; p = 0.05; late, 97 +/-
      30 cm/sec vs 68 +/- 23 cm/sec; p < 0.0001), a higher time-velocity integral in
      early diastole (18.2 +/- 4.8 cm vs 15.1 +/- 4.3 cm; p = 0.006), a significantly
      shorter exercise duration (4.5 +/- 4.1 minutes vs 8.0 +/- 3.9 minutes; p <
      0.0001), a greater degree of functional aerobic impairment (25% +/- 48% vs 2% +/-
      33%; p = 0.02), and a smaller increase in cardiac output with exercise (5.4 +/-
      3.5 L/min vs 8.0 +/- 4.3 L/min; p = 0.01), in spite of similar peak heart rate
      and blood pressure responses. In these asymptomatic subjects with aortic
      stenosis, women had smaller, relatively hypercontractile ventricles, a different
      diastolic filling profile, more exercise limitation, and poorer functional
      capacity. These findings demonstrate the importance of gender in the response of
      the left ventricle to chronic pressure overload.

PMID- 8554027
TI  - Prospective phase I/II studies of definitive irradiation and chemotherapy for
      advanced gynecologic malignancies.
AB  - PURPOSE: This is a prospective study to evaluate toxicity and efficacy of
      concurrent irradiation and three cycles of chemotherapy bolus cisplatin and
      infusion 5-fluorouracil (5FU) in patients with advanced gynecologic malignancies.
      MATERIALS AND METHODS: Patients received cisplatin, 50 mg/m2 I.V. rapid infusion,
      and 5-day continuous infusion of 5FU (750 mg/m2 per day (schedule A); or
      cisplatin 75 mg/m2 i.v. rapid infusion, and 4-day continuous infusion of 5FU
      1,000 mg/m2 per day (schedule B). Schedule A was given to 25 patients in the
      first 36 months of the study and was changed to schedule B in an additional 42
      patients. All patients received irradiation, which usually consisted of 20 Gy
      whole pelvis, 30-40 Gy split field, and two intracavitary insertions for a total
      of 80-90 Gy to point A. Primary cervical cancer occurred in 40 patients with 3
      having stage IB bulky, 2 with stage IIA, 5 with stage IIB, 2 with stage IIIA, 23
      with stage IIIB, 4 with stage IV, and 1 with stage IVB. Recurrent cervical
      carcinoma after radical hysterectomy occurred in 18 patients. The remainder of
      the patients consisted of two each with stages III and IV endometrial carcinoma,
      two with stage III vaginal carcinoma, two with stage III vulvar carcinoma, and
      one with recurrent vulvar carcinoma. Patients were treated from 1985 through
      1992. RESULTS: The 5-year overall survivals for patients with stages IB (bulky)
      IIB cervical cancer was 70%, 25% for stages IIIA-IVA, and 39% for patients with
      recurrent cervical carcinoma. All four patients with endometrial carcinoma have
      recurred and died. Two patients with vulvar carcinoma are alive and free of
      disease, and one is dead of intercurrent disease. One patient with stage III
      vaginal carcinoma is alive and free of disease, while the other recurred and
      died. No significant differences were observed in the toxicity of the two
      chemotherapy schedules. There were 9/39 (23%) grade 4 and one fatal complication
      in those with primary cervical carcinoma. The overall fistulae rate was 11%
      (4/39) with three patients developing rectovaginal fistulae and one having
      vesicovaginal fistula. CONCLUSION: Concurrent chemotherapy and irradiation for
      advanced gynecologic malignancies as administered in this study is highly toxic
      and fails to demonstrate an obvious survival improvement.

PMID- 8554028
TI  - Induction chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (CAP) in
      a combined modality approach for locally advanced and inflammatory breast cancer.
      Long-term results.
AB  - Thirty-one patients with locally advanced and inflammatory breast carcinoma
      (stage IIIA and IIIB) were treated with a combined modality approach between 1985
      and 1989. All patients received as induction chemotherapy a combination of
      cisplatin, doxorubicin, and cyclophosphamide (CAP). Responsive patients and
      patients with operable stable disease underwent modified radical mastectomy
      followed by concurrent radiotherapy and CMF (cyclophosphamide, methotrexate, 5
      fluorouracil) adjuvant chemotherapy. Thirty patients were evaluable for response
      to CAP. The rate of objective response to induction chemotherapy was 76.7% with 2
      patients (6.7%) obtaining a complete response and 21 patients (70%) a partial
      response. Twenty-five patients were rendered disease-free after induction
      chemotherapy and surgery. Only 2 of these had pathological complete response
      (8%). The median overall survival was 48.7 months, the median time to progression
      was 22.4 months and the median disease-free survival was 29.1 months. The
      patients with noninflammatory breast tumor had a significantly better overall
      survival, disease-free survival, and time to progression. The overall survival
      and the time to progression were statistically superior in patients with primary
      tumor size < or = 8 cm. At a median follow-up of 6 years, 29% (95% CI, 13.05 to
      45.01) of patients were alive and 28% (95% CI, 10.4 to 45.6) were disease-free.
      This combined modality treatment seems feasible with quite acceptable toxicity;
      the CAP combination is an effective alternative to the other standard
      chemotherapeutic regimens. Our results, although encouraging, are still poor, and
      new drugs and strategies are required to improve the long-term outcome.

PMID- 8554029
TI  - Chemotherapy of Mediterranean abdominal lymphoma. Retrospective comparison of
      chemotherapy protocols in Iranian patients.
AB  - Retrospectively, 41 Iranian patients with Mediterranean abdominal lymphoma (MAL)
      were studied; 21 patients had received anthracycline-based protocols, and 20
      patients had been treated with regimens lacking anthracyclines. The study groups
      were comparable with respect to several factors, including age, performance
      status, histology of lymphoma, stage of disease, and the average relative dose
      intensity of their protocols. Our first group had a complete remission (CR) rate
      of 62%, mean disease-free interval (DFI) of 16.3 months and a 71% overall
      survival at 30 months. The second group showed a CR rate of 40%, mean DFI of 11.2
      months, and a 35% overall survival at 30 months. The differences were significant
      in survival (P = .012) and DFI (p < .001). The incidence of serious toxicities
      and complications was similar.

PMID- 8554030
TI  - Leucovorin and high-dose fluorouracil in metastatic prostate cancer. A phase II
      trial of the piedmont Oncology Association.
AB  - We performed a Phase II trial of oral leucovorin and high-dose fluorouracil (5FU)
      in hormone refractory patients with metastatic prostate cancer who had not had
      prior chemotherapy. 5FU was given as a 24-hour infusion at a dosage of 4 g/m2 and
      oral leucovorin at a dosage of 50 mg every 6 hours for four doses, starting with
      the infusion of 5FU. Fifteen patients were treated and three were not evaluable
      for response. There were no complete (CR) or partial responses (PR) in 12
      evaluable patients (95% confidence interval for CR+PR of 0 to 26%). Three
      patients had stable disease and the remainder progressed. Toxicities were
      generally mild to moderate, but one patient died of sepsis while neutropenic.
      This dose and schedule of leucovorin and 5FU is not better than single-agent 5FU
      in patients with metastatic prostate cancer.

PMID- 8554031
TI  - A phase II trial of 5-fluorouracil and 1-leucovorin in patients with metastatic
      colorectal cancer.
AB  - We undertook a multicenter phase II trial of 5-fluorouracil (5FU) + 1-leucovorin
      (1-LV) in previously untreated patients with metastatic colorectal cancer to
      determine the response rate, response duration, time to progression, survival,
      and toxicity. Patients were treated with i.v. 5FU 370 mg/m2/day and 1-LV 100
      mg/m2/day x 5 every 28 days. Toxicity and response were determined by WHO
      criteria. One hundred and twenty-six patients were entered, and 119 patients were
      eligible and evaluable. Eighty-eight patients had colon cancer and 37 had rectal
      cancer. The male:female ratio was 58:68. The mean age was 62.2 years. ECOG
      performance status distribution was 0 (39.7%), 1 (46%), and 2 (11.9%). The median
      number of courses of therapy administered was 4.5. Severe- or life-threatening
      stomatitis or diarrhea, nausea, and granulocytopenia occurred in 17.6, 23.2,
      17.6, and 15.9% of patients, respectively. The response rate was 22/119 [18.5%;
      95% confidence interval (CI) of 12.0-26.6]. Median response duration was 188 days
      (95% CI of 111-248 days). Median survival was 379 days (95% confidence interval
      of 289-452 days). These results indicate that when 1-LV is combined with 5FU,
      toxicity is similar in pattern and severity to that of the d,1 racemic mixture.
      The overall efficacy of 1-LV + 5FU is comparable to a recent metaanalysis.

PMID- 8554032
TI  - Stevens-Johnson syndrome resulting from whole-brain radiation and phenytoin.
AB  - Phenytoin, one of the most widely prescribed anticonvulsants, and steroids are
      routinely utilized for seizure prophylaxis in patients with various intracranial
      tumors. We report a case of severe Stevens-Johnson syndrome (SJS), documented by
      biopsy, which occurred in a patient, with metastatic squamous cell carcinoma
      receiving phenytoin, whole-brain radiation therapy (WBRT), and a tapering steroid
      dose. The pathogenesis and implications are then briefly discussed.

PMID- 8554033
TI  - Study of 45 cases of nasopharyngeal carcinoma with dermatomyositis.
AB  - The authors have conducted a study of 61 cases of nasopharyngeal carcinoma (NPC)
      with dermatomyositis (DM) admitted to the hospital between April 1964 and May
      1989 and accounting for 0.027% (61/226, 183) of all the malignant tumors at the
      hospital and 0.086% (61/70,899) of the nasopharyngeal carcinoma cases, during
      that time period. We have analyzed 45 cases with complete data, using equal
      number of age-, sex-, and stage-matched cases with only NPC as control. The
      findings show a 5- and 10-year survival rate and distant metastatic rate of 50.4,
      34.5, and 40.5% respectively, for NPC with DM, and 57.8, 55.2, and 56.5% for
      controls. The results indicated that the radiotherapy with prednisone treatment
      not only is quite effective but also will not result in a significantly increased
      rate of distant metastasis.

PMID- 8554034
TI  - The curative potential of radiation therapy in the treatment of primary vaginal
      carcinoma.
AB  - The outcome of 55 patients with primary vaginal carcinoma treated with radiation
      therapy at Roswell Park Cancer Institute was retrospectively reviewed. Forty-four
      (80%) had a squamous cell carcinoma and 11 (20%) had an adenocarcinoma. The
      median age was 61 years and the median dose of radiation administered, external
      beam and brachytherapy, was 7,040 cGy. Fifteen percent of patients developed
      severe radiation-induced complications, and 36% developed recurrence of disease.
      The overall 5-year survival and 5-year disease-free survival for the entire group
      was 49 and 58%, respectively. Variables positively influencing survival included
      younger age, early stage, involvement of the upper vagina, total radiation dosage
      > 7,500 cGy, and the use of combination external beam and brachytherapy. However,
      only age acted as an independent prognostic factor affecting survival. The pelvis
      was the site of disease in the majority of patients who suffered recurrence.

PMID- 8554035
TI  - Gastric cancer in young patients who underwent curative resection. Comparative
      study with older patients.
AB  - Although several studies demonstrated the poor prognosis of young patients with
      gastric cancer, there were few reports about the survival of young patients who
      underwent radical surgery. We retrospectively reviewed the hospital records of
      697 patients with curatively resected locally advanced gastric cancer to compare
      the pathologic findings and prognosis of young patients (aged < 40 years; 91
      patients) with those of older (aged > or = 40 years; 606 patients) patients.
      There were no significant differences in location of tumors, Borrmann types,
      tumor invasion, and pathologic stage between both age groups. Despite the male
      predominance in older patients, the male-to-female ratio was nearly equal in
      young patients (p = 0.022). A significantly higher percentage of young patients
      showed poorly differentiated histology including signet ring cell and
      undifferentiated carcinoma than older patients (p < 0.0001). Adjuvant
      chemotherapy was more frequently performed in the young patients with a variety
      of different regimens (85.7 vs. 72.3%; p = 0.009). The 5-year overall survival
      rate revealed no statistically significant differences between the young and
      older patients (53.1 vs. 56.6%; p = 0.820). In conclusion, the young patients
      with curatively resected locally advanced gastric cancer showed similar survival
      compared to that of older patients.

PMID- 8554036
TI  - Computed tomography features of cerebral spread of malignant melanoma.
AB  - The CT features of cerebral involvement by metastatic malignant melanoma are
      described in 28 patients. The most common locations of the primary lesion were
      the trunk and lower limbs. There was a high incidence of extracerebral metastasis
      at the time of diagnosis of cerebral involvement. Headache and behavioral changes
      were the most frequent presenting symptoms; 7% of patients with asymptomatic. The
      cerebral metastases were classified by size (< 1 cm, 1-4 cm, > 4 cm), with more
      than half measuring 1-4 cm. The larger lesions usually occurred singly.
      Peritumoral edema was detected in 89% of patients, hemorrhage in 19%, pressure
      signs on the ventricles in 37%, midline deviation in 15%, and leptomeningeal
      spread in 11%. No correlation was noted between size of tumor and other
      radiological features. Unilateral involvement was documented in 44% of cases. In
      the majority of patients the metastases were located at the periphery of the
      brain, mostly in the temporal and parietal lobes. Neuroimaging studies of the
      brain in asymptomatic patients with malignant melanoma may reveal occult
      metastases and influence the choice of treatment.

PMID- 8554037
TI  - Correlation of flow cytometry to clinical factors, hormone receptors, and
      histopathological grade in stage I and II invasive breast carcinoma.
AB  - DNA index (ploidy) and S-phase fraction (SPF) were measured by flow cytometry in
      131 invasive stage I and II breast carcinomas. Ploidy showed a strong correlation
      with SPF (p = 0.0001), with aneuploid tumors having a high SPF. Both cytometric
      parameters correlated with tumor size and hormonal receptor status. Smaller
      tumors tended to be diploid and have low SPF. Nodal status did not demonstrate an
      association with cytometric findings. There was a highly significant connection
      between tumor grade, especially nuclear grade, and SPF (p = 0.0001). The study
      demonstrates the relationship between conventional prognostic factors, DNA
      content, and proliferative activity of breast tumors.

PMID- 8554038
TI  - Postirradiation sarcoma of the gynecologic tract. A report of 13 cases and a
      discussion of the risk of radiation-induced gynecologic malignancies.
AB  - With improvement in survival after cancer treatment, it is becoming increasingly
      important to examine treatment-related morbidity and mortality. Sarcomas can
      develop within the irradiated field after radiation therapy (RT) for gynecologic
      malignancies. We undertook a study to assess the outcome after treatment of
      postirradiation sarcoma (PIS) of the gynecologic tract. In reviewing our data and
      the literature, we compare the absolute risk of PIS and other radiation
      associated second malignant neoplasms (SMNs) with the mortality risk of surgery
      and general anesthesia. Between 1955 and 1987, 114 patients with uterine sarcomas
      were seen at the University of California, Los Angeles (UCLA), Medical Center.
      Thirteen had a prior history of RT. Conditions for which these patients received
      RT included choriocarcinoma (one), menorraghia (four), cervical cancer (six), and
      ovarian cancer (two). RT doses were known in six cases and ranged from 4,000 to
      8,000 cGy. Latency time from RT to the development of PIS ranged from 3 to 30
      years, with a median of 17 years. Twelve patients were treated with surgery or
      additional RT. Two patients remain alive 5 months and 57 months, respectively,
      following salvage therapy. Five-year disease-specific survival for all patients
      is 17%. From our data and a review of the literature, we estimate that the
      absolute risk of PIS with long-term follow-up ranges from 0.03 to 0.8%.
      Postirradiation sarcoma of the gynecologic tract is a relatively rate event
      associated with a poor prognosis. Mortality risks of radiation-associated SMN are
      similar to mortality risks of surgery and general anesthesia. Given the large
      number of patients with gynecologic malignancies who can be cured or palliated
      with RT, concern regarding radiation sarcomagenesis should not be a major factor
      influencing treatment decisions.

PMID- 8554039
TI  - The prognostic value of PSA levels in radiation therapy of patients with
      carcinoma of the prostate: the UCLA experience 1988-1992.
AB  - BACKGROUND AND OBJECTIVES: Pretreatment prostate-specific antigen (PSA) levels
      may be of prognostic significance for patients with prostate cancer.
      Posttreatment PSA data are more limited. This study was undertaken to examine the
      prognostic role of pretreatment and posttreatment PSA levels in the radiation
      treatment of patients with carcinoma of the prostate. METHODS: One hundred one
      patients who received primary radiation therapy at UCLA between 1988 and 1992 for
      clinical stage A to D1 prostate cancer were analyzed. Included were 4 patients
      with stage A, 77 with stage B, 16 with stage C, and 4 with stage D. All patients
      had pretherapy and posttherapy PSA values. Patients received definitive radiation
      therapy with photons (81), neutrons (13), or interstitial implant (7).
      Correlations were made with other prognostic factors and treatment outcome.
      RESULTS: Median follow-up was 28 months. At last follow-up, 64% were without
      evidence of disease, 17% had rising PSA profiles or failure of PSA to normalize
      (chemical failure), and 19% had local recurrence and/or distant metastases. The 4
      year overall survival was 85%, whereas actuarial survival free of chemical or
      clinical failure was only 32%. Pretreatment PSA levels and posttreatment PSA
      level normalization at 6 months correlated significantly with disease-free
      survival. On univariate analysis, pretreatment PSA levels correlated
      significantly with stage, high versus low Gleason score, and outcome.
      Posttreatment PSA level normalization at 6 and 12 months correlated with stage,
      pretreatment PSA level, and outcome, but not with Gleason score. Only PSA level
      normalization at 6 months and age were independent variables using multivariate
      analysis. PSA nadir values differed significantly between patients free of
      disease and those who failed. CONCLUSIONS: In our analysis, posttreatment PSA
      levels were independently predictive of outcome, whereas pretreatment PSA levels,
      while correlating with other prognostic factors, were not independently
      predictive. Given the prognostic value of posttreatment PSA levels, it is
      appropriate that chemical failures be included in outcome analyses, although this
      will lower disease-free survival.

PMID- 8554040
TI  - A phase II trial of merbarone (NSC 336628) in the treatment of recurrent
      epithelial ovarian carcinoma. A Gynecologic Oncology Group Study.
AB  - BACKGROUND: Patients with recurrent epithelial ovarian carcinoma who progress
      through a cisplatin-based regimen or recur less than 6 months after discontinuing
      cisplatin, have limited therapeutic options. The Gynecologic Oncology Group
      conducted a Phase II trial of merbarone in this patient population. METHODS:
      Twenty-seven patients with recurrent epithelial ovarian carcinoma who had
      previously received one prior cisplatin-based regimen were scheduled to receive
      1000 mg/m2 of merbarone by continuous intravenous infusion through a central line
      each day for five days every four weeks. RESULTS: Of the 27 patients entered, one
      was ineligible because of wrong primary, and two never received the drug, leaving
      24 patients evaluable for toxicity. Twenty of 24 were evaluable for response. The
      regimen was well tolerated with only one episode each of GOG grade 3 leukopenia
      (4%) or grade 4 granulocytopenia (4%). There was one episode (4%) of GOG grade 3
      gastrointestinal toxicity. Prior to increasing the infusate concentration to 4
      mg/ml, there was one episode (4%) of altered mental status which, in retrospect,
      may have been secondary to iatrogenic hyponatremia. There were two partial
      responses (10%) (95% confidence interval 1.2-31.7%). CONCLUSIONS: Merbarone
      exhibited minimal activity at this schedule in this pretreated group of patients
      with epithelial ovarian carcinoma.

PMID- 8554041
TI  - Postoperative radiotherapy of medulloblastoma. Impact of radiation quality on
      treatment outcome.
AB  - Between 1975 and 1991, 40 patients with newly diagnosed medulloblastoma of the
      posterior fossa were treated at the authors' institutions. After aggressive
      surgical resection 39/40 patients (98%) received craniospinal radiation therapy
      (RT), including a local boost. A group of 29 patients was treated with adjuvant
      chemotherapy. The estimated overall 5-year survival and 5-year relapse-free
      survival (RFS) probabilities were 75% and 65%, respectively. The 5-year survival
      was significantly prolonged for patients treated after 1981 as compared to those
      treated between 1975 and 1980 (80% vs 64%, p = .02). However, multivariate
      analysis identified the adequate coverage of the target volume by external RT as
      the only significant variable (p = .0031). The extent of resection, stage
      according to Chang, radiation dose to the posterior fossa (< 55 Gy vs > or = 55
      Gy) and the use of chemotherapy did not significantly influence survival and RFS.
      The initial site of recurrence was the posterior fossa with or without
      disseminated central nervous system (CNS) disease in 5 patients, the CNS without
      posterior fossa in 4 patients, and the bone marrow in 2 patients. An isolated
      frontal relapse occurred in 1 patient. We conclude that quality control of RT
      plays a decisive role in the long-term outcome of patients with medulloblastoma.

PMID- 8554042
TI  - Accelerated epirubicin-ifosfamide-dacarbazine regimen in patients with adult soft
      tissue sarcomas.
AB  - BACKGROUND: Neutropenia and infections are the dose-limiting toxicities of the
      EID regimen and can cause dose reduction and/or delay in chemotherapy
      administration. The purpose of this study was to verify if EID + G-CSF is
      feasible with an acceptable toxicity in a day hospital setting and if G-CSF could
      allow an increase in the dose intensity of the EID regimen by shortening the
      intervals between the courses. PATIENTS AND METHODS: 20 patients with inoperable
      primary, metastatic or residual disease after surgery or at high risk of
      recurrence after complete resection, histologically confirmed adult soft tissue
      sarcoma, entered the study. The dose and schedule of the chemotherapy agents were
      epidoxorubicin 30 mg/m2 days 1, 2, 3, dacarbazine 300 mg/m2 days 1, 2, 3, and
      ifosfamide 2500 mg/m2 with mesna uroprotection days 1, 2, 3. G-CSF, 300
      micrograms/day subcutaneously, was administered from day 7 for a maximum of 14
      days and discontinued when WBC was greater than 10 x 10(9)/L. Courses were
      repeated "as soon as possible," but never earlier than 10 days from the previous
      course and at least 48 hours after the last G-CSF injection. RESULTS: A total of
      66 EID + G-CSF courses were administered. A G3 and G4 (WHO) neutropenia occurred
      in 66% of evaluables courses. Nonhematological toxicity was mild. The median
      number of G-CSF injections required during any interval between courses was 9
      (range: 4-14 injections) and the median interval between courses was 21 days
      (range: 13-36 days). The median dose intensity at the third course of
      chemotherapy was 1.15 (range: 0.71-1.62). CONCLUSION: This study shows that G-CSF
      allows a moderate increase in the delivered dose intensity of chemotherapy with
      an acceptable toxicity. Further studies are needed to investigate if this
      increase in DI may translate into an improved response rate.

PMID- 8554043
TI  - Intermediate doses of cyclophosphamide alone or following adriamycin in advanced
      breast cancer. A pilot study.
AB  - Cyclophosphamide (CTX) is an active drug in breast cancer and presents a well
      established dose-response relationship. To explore further this relationship, the
      present pilot study investigated the therapeutic efficacy of cyclophosphamide at
      intermediate dose in two groups of untreated patients with advanced breast
      cancer. Nine women received the drug alone at 3-4 g/m2 i.v. every 2 weeks for a
      total of three doses. The same dose schedule was also given to 11 women following
      the administration of four cycles of Adriamycin, at 75 mg/m2 i.v. every 3 weeks.
      We documented one partial remission in untreated women and four partial responses
      in Adriamycin-treated patients. The major toxicity was represented by leukopenia
      and neutropenia. Myelosuppression was relevant but of short duration, and the use
      of G-CSF appeared useful in controlling this side effect. In spite of the high
      dose intensity of the present cyclophosphamide dose schedule (9 g/m2 in 4 weeks),
      i.e., almost three times superior to that conventionally employed, present
      results do not suggest its superiority over the current chemotherapeutic regimens
      utilized in advanced disease.

PMID- 8554044
TI  - Kaposi's sarcoma on a lymphedematous arm after mastectomy.
AB  - Two patients with Kaposi's sarcoma developing in an area of lymphedematous arm
      postmastectomy are reported. The Kaposi's sarcoma occurred after latent periods
      of 26 and 7 years following radical and modified-radical mastectomy,
      respectively, in the edematous tissue of the ipsilateral arm. The cutaneous
      nodules were purple in color and ranged in size from a few millimeters to > 1 cm
      in diameter. The results of routine laboratory tests were all within normal
      limits. Human immunodeficiency virus (HIV) antibody and cytomegalovirus (CMV)
      antigen, using enzyme-linked immunosorbent assay (ELISA), were negative.

PMID- 8554045
TI  - 1995 William Allan Award address. Human genetics: a discipline at risk for
      fragmentation.

PMID- 8554047
TI  - Genetic heterogeneity in Niemann-Pick C disease: a study using somatic cell
      hybridization and linkage analysis.
AB  - The primary molecular defect underlying Niemann-Pick C disease (NPC) is still
      unknown. A wide spectrum of clinical and biochemical phenotypes has previously
      been documented. Indication of genetic heterogeneity has recently been provided
      for one patient. In the present study, somatic cell hybridization experiments
      were carried out on skin fibroblast cultures from 32 unrelated NPC patients
      covering the range of known clinical and biochemical phenotypes. The criterion
      for complementation was the restoration of a normal intracellular fluorescent
      pattern in polykaryons stained with filipin to document cholesterol distribution.
      Crosses between the various cell lines revealed a major complementation group
      comprising 27 unrelated patients and a second minor group comprising 5 patients.
      Linkage analysis in one multiplex family belonging to the minor complementation
      group showed that the mutated gene does not map to the 18q11-12 region assigned
      to the major gene. Patients in the first group spanned the whole spectrum of
      clinical and cellular phenotypes. No consistent clinical or biochemical
      phenotypes was associated with the second complementation group. Three of the
      five group 2 patients, however, presented with a new rare phenotype associated
      with severe pulmonary involvement leading to death within the first year of life.
      No biochemical abnormality specific of either group could be demonstrated with
      regard to tissue lipid storage pattern, intralysosomal cholesterol storage, and
      regulation of cholesterol homeostasis. Mutations affecting at least two different
      genes have thus been shown to underlie NPC. The two gene products may function
      together or sequentially in a common metabolic pathway affecting intracellular
      cholesterol transport.

PMID- 8554046
TI  - Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17
      kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus.
AB  - Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant
      disorder characterized by progressive postnatal deficiency of arginine
      vasopressin as a result of mutation in the gene that encodes the hormone. To
      determine the extent of mutations in the coding region that produce the
      phenotype, we studied members of 17 unrelated kindreds with the disorder. We
      sequenced all 3 exons of the gene by using a rapid, direct dye-terminator method
      and found the causative mutation in each kindred. In four kindreds, the mutations
      were each identical to mutations described in other affected families. In the
      other 13 kindreds each mutation was unique. There were two missense mutations
      that altered the cleavage region of the signal peptide, seven missense mutations
      in exon 2, which codes for the conserved portion of the protein, one nonsense
      mutation in exon 2, and three nonsense mutations in exon 3. These findings,
      together with the clinical features of FNDI, suggest that each of the mutations
      exerts an effect by directing the production of a pre-prohormone that cannot be
      folded, processed, or degraded properly and eventually destroys vasopressinergic
      neurons.

PMID- 8554048
TI  - Fine mapping of the EDA gene: a translocation breakpoint is associated with a CpG
      island that is transcribed.
AB  - In order to identify the gene for human X-linked anhidrotic ectodermal dysplasia
      (EDA), a translocation breakpoint in a female with t(X;1)(q13.1;p36.3) and EDA
      (patient AK) was finely mapped. The EDA region contains five groups of rare
      cutter restriction sites that define CpG islands. The two more centromeric of
      these islands are associated with transcripts of 3.5 kb and 1.8 kb. The third CpG
      island maps within <1 kb of the translocation breakpoint in patient AK, as
      indicated by a genomic rearrangement, and approximately 100 kb centromeric from
      another previously mapped translocation breakpoint (patient AnLy). Northern
      analysis with a probe from this CpG island detected an approximately 6-kb mRNA in
      several fetal tissues tested. An extended YAC contig of 1,200 kb with an average
      of fivefold coverage was constructed. The two most telomeric CpG islands map 350
      kb telomeric of the two translocations. Taken together, the results suggest that
      the CpG island just proximal of the AK translocation breakpoint lies at the 5'
      end of a candidate gene for EDA.

PMID- 8554049
TI  - Molecular definition of red cell Rh haplotypes by tightly linked SphI RFLPs.
AB  - The Rh blood group system of human red cells contains five major antigens D, C/c,
      and E/e (the latter four designated "non-D") that are specified by eight gene
      complexes known as Rh haplotypes. In this paper, we report on the mapping of RH
      locus and identification of a set of SphI RFLPs that are tightly linked with the
      Rh structural genes. Using exon-specific probes, we have localized the SphI
      cleavage sites resulting in these DNA markers and derived a comprehensive map for
      the RH locus. It was found that the SphI fragments encompassing exons 4-7 of the
      Rh genes occur in four banding patterns or frameworks that correspond to the
      distribution and segregation of the common Rh haplotypes. This linkage
      disequilibrium allowed a genotype-phenotype correlation and direct determination
      of Rh zygosity related to the Rh-positive or Rh-negative status (D/D, D/d, and
      d/d). Studies on the occurrence of SphI RFLPs in a number of rare Rh variants
      indicated that Rh phenotypic diversity has taken place on different haplotype
      backgrounds and has arisen by diverse genetic mechanisms. The molecular
      definition of Rh haplotypes by SphI RFLP frameworks should provide a useful
      procedure for genetic counseling and prenatal assessment of Rh alloimmunization.

PMID- 8554050
TI  - PRB1, PRB2, and PRB4 coded polymorphisms among human salivary concanavalin-A
      binding, II-1, and Po proline-rich proteins.
AB  - Six closely linked PRP (proline-rich protein) genes code for many salivary PRPs
      that show frequent length and null variants. From determined protein sequences
      and DNA sequence analysis of variant alleles, we here report the coding and
      molecular basis for Con (concanavalin A-binding) and Po (parotid "o") protein
      polymorphisms. The Con1 glycoprotein is encoded in exon 3 of a PRB2 allele (PRB2L
      CON1+) with a potential N-linked glycosylation site. Because of a probable gene
      conversion encompassing > or = 684 bp of DNA, the "PRB2-like" Con2 glycoprotein
      is encoded in exon 3 of a PRB1 allele (PRB1M CON2+) with a potential
      glycosylation site. The PmF protein is also encoded in the PRB1M CON2+ allele,
      thus explaining the previously reported association between Con2 and PmF
      proteins. A PRB2L CON1 allele contains a single nt missense change [TCT(Ser)-
      >CCT (Pro)] that abolishes the potential N-linked glycosylation site (NKS-->NKP)
      in the Con1 protein, and this explains the Con- type. The Po protein and a
      glycoprotein (II-1) are encoded in the PRB4 gene, and both proteins are absent in
      the presence of a mutation in the PRB4M PO- allele that contains a single nt
      change (G--C) at the +1 invariant position of the intron 3 5'donor splice site.
      The genetically determined absence of the II-1 glycoprotein leads to altered in
      vitro binding of Streptococcus sanguis 10556 to salivary proteins, which suggests
      a biological consequence for null mutations of the PRB4 gene.

PMID- 8554051
TI  - Molecular definition of breakpoints associated with human Xq isochromosomes:
      implications for mechanisms of formation.
AB  - To test the centromere misdivision model of isochromosome formation, we have
      defined the breakpoints of cytogenetically monocentric and dicentric Xq
      isochromosomes (i(Xq)) from Turner syndrome probands, using FISH with cosmids and
      YACs derived from a contig spanning proximal Xp. Seven different pericentromeric
      breakpoints were identified, with 10 of 11 of the i(Xq)s containing varying
      amounts of material from Xp. Only one of the eight cytogenetically monocentric
      i(Xq)s demonstrated a single alpha-satellite (DXZ1) signal, consistent with
      classical models involving centromere misdivision. The remaining seven were
      inconsistent with such a model and had breakpoints that spanned proximal Xp11.21:
      one was between DXZ1 and the most proximal marker, ZXDA; one occurred between the
      duplicated genes, ZXDA and ZXDB; two were approximately 2 Mb from DXZ1; two were
      adjacent to ALAS2 located 3.5 Mb from DXZ1; and the largest had a breakpoint just
      distal to DXS1013E, indicating the inclusion of 8 Mb of Xp DNA between
      centromeres. The three cytologically dicentric i(Xq)s had breakpoints distal to
      DXS423E in Xp11.22 and therefore contained > or = 12 Mb of DNA between
      centromeres. These data demonstrate that the majority of breakpoints resulting in
      i(Xq) formation are in band Xp11.2 and not in the centromere itself. Therefore,
      we hypothesize that the predominant mechanism of i(Xq) formation involves
      sequences in the proximal short arm that are prone to breakage and reunion events
      between sister chromatids or homologous X chromosomes.

PMID- 8554053
TI  - Nutritional ecogenetics: homocysteine-related arteriosclerotic vascular disease,
      neural tube defects, and folic acid.

PMID- 8554052
TI  - Lack of X inactivation associated with maternal X isodisomy: evidence for a
      counting mechanism prior to X inactivation during human embryogenesis.
AB  - We have previously reported functional disomy for X-linked genes in females with
      tiny ring X chromosomes and a phenotype significantly more abnormal than Turner
      syndrome. In such cases the disomy results from failure of these X chromosomes to
      inactivate because they lack DNA sequences essential for cis X inactivation. Here
      we describe a novel molecular mechanism for functional X disomy that is
      associated with maternal isodisomy. In this case, the severe mental retardation
      and multiple congenital abnormalities in a female with a mosaic 45,X/
      46,X,del(X)(q21.3-qter)/ 46X,r(X) karyotype are associated with overexpression of
      the genes within Xpter to Xq21.31 in many of her cells. Her normal X, ring X, and
      deleted linear X chromosomes originate from the same maternal X chromosome, and
      all are transcriptionally active. None expresses X inactive specific transcript
      (XIST), although the locus and region of the putative X inactivation center (XIC)
      are present on both normal and linear deleted X chromosomes. To our knowledge,
      this is the first report of a functional maternal X isodisomy, and the largest X
      chromosome to escape inactivation. In addition, these results (1) show that cis
      inactivation does not invariably occur in human females with two X chromosomes,
      even when the XIC region is present on both of them; (2) provide evidence for a
      critical time prior to the visible onset of X inactivation in the embryo when
      decisions about X inactivation are made; and (3) support the hypothesis that the
      X chromosome counting mechanism involves chromosomal imprinting, occurs prior to
      the onset of random inactivation, and is required for subsequent inactivation of
      the chromosome.

PMID- 8554054
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy, genetic homogeneity, and mapping of the locus within a 2-cM
      interval.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is a recently identified autosomal dominant
      cerebral arteriopathy characterized by the recurrence of subcortical infarcts
      leading to dementia. A genetic linkage analysis conducted in two large families
      recently allowed us to map the affected gene on chromosome 19 in a 12-cM interval
      bracketed by D19S221 and D19S215. In the present study, these first 2 families
      and 13 additional ones, including a total of 199 potentially informative meiosis,
      have been genotyped with eight polymorphic markers located between D19S221 and
      D19S215. All families were linked to chromosome 19. The highest combined lod
      score (Zmax = 37.24 at theta = .01) was obtained with marker D19S841, a new CAn
      microsatellite marker that we isolated from chromosome 19 cosmids. The
      recombinant events observed within these families were used to refine the genetic
      mapping of CADASIL within a 2-cM interval that is now bracketed by D19S226 and
      D19S199 on 19p13.1. These data strongly suggest the genetic homogeneity of this
      recently identified condition and establish the value of its clinical and
      neuroimaging diagnostic criteria. Besides their importance for the ongoing
      positional cloning of the CADASIL gene, these data help to refine the genetic
      mapping of CADASIL relative to familial hemiplegic migraine and hereditary
      paroxysmal cerebellar ataxia, conditions that we both mapped within the same
      chromosome 19 region.

PMID- 8554055
TI  - Familial recurrence-pattern analysis of nonsyndromic isolated cleft palate--a
      Danish Registry study.
AB  - The finding of an association between genetic variation at the transforming
      growth-factor alpha (TGFA) locus and nonsyndromic isolated cleft palate (CP)
      represents a potentially important breakthrough in our understanding of this
      condition. The present study was undertaken to assess the feasibility of
      detecting linkage to putative CP-susceptibility loci, such as TGFA. To this end,
      the familial recurrence pattern for CP was evaluated to determine the most likely
      mode of inheritance for this condition. The study took advantage of the high
      ascertainment and uniform registration of CP in Denmark. In addition, the study
      utilized estimates of familial recurrence that were obtained by register linkage
      and, hence, were not subject to either recall bias or the potentially biasing
      influence of nonresponders. The recurrence risks for first-, second-, and third
      degree relatives of 1,364 nonsyndromic CP probands were estimated to be 2.74%
      (72/2,628), 0.28% (3/1,068), and 0.00% (0/360), respectively. These estimates are
      close to published estimates based on questionnaire and interview data. The
      population prevalence for nonsyndromic CP was, however, found to be considerable
      higher than usually reported (0.058% [1,456/2,523,023]). Analyses of these and
      previously published data, using the method presented by Risch, indicated that
      major-locus or additive multilocus inheritance of CP is unlikely. The familial
      recurrence pattern was, however, consistent with CP being determined by several
      interacting loci. Under such a model, a single locus accounting for more than a
      sixfold increase in the risk to first-degree relatives of CP probands is
      unlikely, whereas a single locus accounting for a threefold increase provided a
      good fit to the data. Such a locus could be detected in a realistic sample of
      affected sib pairs.

PMID- 8554056
TI  - Influence of apolipoprotein E genotype on the transmission of Alzheimer disease
      in a community-based sample.
AB  - The epsilon 4 allele of the apolipoprotein E locus (APOE) has been found to be an
      important predictor of Alzheimer disease (AD). However, linkage analysis has not
      clarified the role of APOE in the transmission of AD. The results of the current
      study provide evidence that the pattern of transmission of memory disorders
      differs in nuclear families in which the AD-affected proband did carry an epsilon
      4 allele versus those families in which the AD-affected proband did not carry an
      epsilon allele. Further, risk of AD due to APOE genotype in the probands is
      modified by family history of memory disorders, suggesting gene-by-gene
      interactions. Family history remained a significant predictor of AD for affected
      probands with some, but not all, APOE genotypes in a logistic regression
      analysis. Though nonadditive in the prediction of AD, APOE genotype and family
      history acted additively in the prediction of age at AD onset. The results of
      complex segregation analysis were inconsistent with Mendelian segregation of
      memory disorders both in families of affected probands who did or did not carry
      an epsilon 4 allele, yet these two groups had significantly different parameter
      estimates for their transmission models. These results are consistent with gene
      by-gene interactions, but also could result from common elements in the familial
      environment.

PMID- 8554057
TI  - Statistical models for trisomic phenotypes.
AB  - Certain genetic disorders are rare in the general population but more common in
      individuals with specific trisomies, which suggests that the genes involved in
      the etiology of these disorders may be located on the trisomic chromosome. As
      with all aneuploid syndromes, however, a considerable degree of variation exists
      within each phenotype so that any given trait is present only among a subset of
      the trisomic population. We have previously presented a simple gene-dosage model
      to explain this phenotypic variation and developed a strategy to map genes for
      such traits. The mapping strategy does not depend on the simple model but works
      in theory under any model that predicts that affected individuals have an
      increased likelihood of disomic homozygosity at the trait locus. This paper
      explores the robustness of our mapping method by investigating what kinds of
      models give an expected increase in disomic homozygosity. We describe a number of
      basic statistical models for trisomic phenotypes. Some of these are logical
      extensions of standard models for disomic phenotypes, and some are more specific
      to trisomy. Where possible, we discuss genetic mechanisms applicable to each
      model. We investigate which models and which parameter values give an expected
      increase in disomic homozygosity in individuals with the trait. Finally, we
      determine the sample sizes required to identify the increased disomic
      homozygosity under each model. Most of the models we explore yield detectable
      increases in disomic homozygosity for some reasonable range of parameter values,
      usually corresponding to smaller trait frequencies. It therefore appears that our
      mapping method should be effective for a wide variety of moderately infrequent
      traits, even though the exact mode of inheritance is unlikely to be known.

PMID- 8554058
TI  - Chromosomal duplications in bacteria, fruit flies, and humans.

PMID- 8554059
TI  - Segregation analysis of continuous phenotypes by using higher sample moments.
AB  - The present article discusses the use of computational methods based on
      generalized estimating equations (GEE), as a potential alternative to full
      maximum-likelihood methods, for performing segregation analysis of continuous
      phenotypes by using randomly selected family data. The method that we propose can
      estimate effect and degree of dominance of a major gene in the presence of
      additional nongenetic or polygenetic familial associations, by relating sample
      moments to their expectations calculated under the genetic model. It is known
      that all parameters in basic major-gene models cannot be identified, for
      estimation purposes, solely in terms of the first two sample moments of data from
      randomly selected families. Thus, we propose the use of higher (third order)
      sample moments to resolve this identifiability problem, in a pseudo-profile
      likelihood estimation scheme. In principle, our methods may be applied to fitting
      genetic models by using complex pedigrees and for estimation in the presence of
      missing phenotype data for family members. In order to assess its statistical
      efficiency we compare several variants of the method with each other and with
      maximum-likelihood estimates provided by the SAGE computer package in a
      simulation study.

PMID- 8554060
TI  - Error detection for genetic data, using likelihood methods.
AB  - As genetic maps become denser, the effect of laboratory typing errors becomes
      more serious. We review a general method for detecting errors in pedigree
      genotyping data that is a variant of the likelihood-ratio test statistic. It
      pinpoints individuals and loci with relatively unlikely genotypes. Power and
      significance studies using Monte Carlo methods are shown by using simulated data
      with pedigree structures similar to the CEPH pedigrees and a larger experimental
      pedigree used in the study of idiopathic dilated cardiomyopathy (DCM). The
      studies show the index detects errors for small values of theta with high power
      and an acceptable false positive rate. The method was also used to check for
      errors in DCM laboratory pedigree data and to estimate the error rate in CEPH
      chromosome 6 data. The errors flagged by our method in the DCM pedigree were
      confirmed by the laboratory. The results are consistent with estimated false
      positive and false-negative rates obtained using simulation.

PMID- 8554061
TI  - Reverse mutation in fragile X syndrome.

PMID- 8554062
TI  - Exclusion of linkage between cleft lip with or without cleft palate and markers
      on chromosomes 4 and 6.

PMID- 8554063
TI  - Multiple mutations in a specific gene in a small geographic area: a common
      phenomenon?

PMID- 8554064
TI  - The distinction between juvenile and adult-onset primary open-angle glaucoma.

PMID- 8554065
TI  - The gene responsible for a severe form of peripheral neuropathy and agenesis of
      the corpus callosum maps to chromosome 15q.
AB  - Peripheral neuropathy with or without agenesis of the corpus callosum (ACCPN) is
      a devastating neurodegenerative disorder that is transmitted as an autosomal
      recessive trait. Genealogical studies in a large number of affected French
      Canadian individuals suggest that ACCPN results from a single founder mutation. A
      genomewide search using 120 microsatellite DNA markers in 14 French Canadian
      families allowed the mapping of the ACCPN gene to a 5-cM region on chromosome
      15q13-q15 that is flanked by markers D15S1040 and D15S118. A maximum two-point
      LOD score of 11.1 was obtained with the marker D15S971 at a recombination
      fraction of 0. Haplotype analysis and linkage disequilibrium support a founder
      effect. These findings are the first step in the identification of the gene
      responsible for ACCPN, which may shed some light on the numerous conditions
      associated with the progressive peripheral neuropathy or agenesis of the corpus
      callosum.

PMID- 8554066
TI  - Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the
      methylenetetrahydrofolate reductase gene is a genetic risk factor for
      cardiovascular disease.
AB  - Mild hyperhomocysteinemia is an established risk factor for cardiovascular
      disease. Genetic aberrations in the cystathionine beta-synthase (CBS) and
      methylenetetrahydrofolate reductase (MTHFR) genes may account for reduced enzyme
      activities and elevated plasma homocysteine levels. In 15 unrelated Dutch
      patients with homozygous CBS deficiency, we observed the 833T-->C (I278T)
      mutation in 50% of the alleles. Very recently, we identified a common mutation
      (677C-->T; A-->V) in the MTHFR gene, which, in homozygous state, is responsible
      for the thermolabile phenotype and which is associated with decreased specific
      MTHRF activity and elevated homocysteine levels. We screened 60 cardiovascular
      patients and 111 controls for these two mutations, to determine whether these
      mutations are risk factors for premature cardiovascular disease. Heterozygosity
      for the 833T-->C mutation in the CBS gene was observed in one individual of the
      control group but was absent in patients with premature cardiovascular disease.
      Homozygosity for the 677C-->T mutation in the MTHFR gene was found in (15%) of 60
      cardiovascular patients and in only 6 (approximately 5%) of 111 control
      individuals (odds ratio 3.1 [95% confidence interval 1.0-9.2]). Because of both
      the high prevalence of the 833T-->C mutation among homozygotes for CBS deficiency
      and its absence in 60 cardiovascular patients, we may conclude that
      heterozygosity for CBS deficiency does not appear to be involved in premature
      cardiovascular disease. However, a frequent homozygous mutation in the MTHFR gene
      is associated with a threefold increase in risk for premature cardiovascular
      disease.

PMID- 8554067
TI  - A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families.
AB  - We have analyzed 20 breast-ovarian cancer families, the majority of which show
      positive evidence of linkage to chromosome 17q12 for germ-line mutations in the
      BRCA1 gene. BRCA1 mutations cosegregating with breast and ovarian cancer
      susceptibility were identified in 16 families, including 1 family with a case of
      male breast cancer. Nine of these mutations have not been reported previously.
      The majority of mutations were found to generate a premature stop codon leading
      to the formation of a truncated BRCA1 protein of 2%-88% of the expected normal
      length. Two mutations altered the RING finger domain. Sequencing of genomic DNA
      led to the identification of a mutation in the coding region of BRCA1 in 12
      families, and cDNA analysis revealed an abnormal or missing BRCA1 transcript in 4
      of the 8 remaining families. A total of eight mutations were associated with a
      reduced quantity of BRCA1 transcript. We were unable to detect BRCA1 mutations in
      4 of the 20 families, but only 1 of these was clearly linked to BRCA1. It is
      expected that the majority of clear examples of the breast-ovarian syndrome will
      be associated with germ-line mutations in the coding region of BRCA1.

PMID- 8554068
TI  - Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE)
      gene.
AB  - The silent phenotype of human butyrylcholinesterase (BChE), present in most human
      populations in frequencies of approximately 1/100,000, is characterized by the
      complete absence of BChE activity or by activity <10% of the average levels of
      the usual phenotype. Heterogeneity in this phenotype has been well established at
      the phenotypic level, but only a few silent BCHE alleles have been characterized
      at the DNA level. Twelve silent alleles of the human butyrylcholinesterase gene
      (BCHE) have been identified in 17 apparently unrelated patients who were selected
      by their increased sensitivity to the muscle relaxant succinylcholine. All of
      these alleles are characterized by single nucleotide substitutions or deletions
      leading to distinct changes in the structure of the BChE enzyme molecule. Nine of
      the nucleotide substitutions result in the replacement of single amino acid
      residues. Three of these variants, BCHE*33C, BCHE*198G, and BCHE*201T, produce
      normal amounts of immunoreactive but enzymatically inactive BChE protein in the
      plasma. The other six amino acid substitutions, encoded by BCHE*37S, BCHE*125F,
      BCHE*170E, BCHE*471R, and BCHE*518L, seem to cause reduced expression of BChE
      protein, and their role in determining the silent phenotype was confirmed by
      expression in cell culture. The other four silent alleles, BCHE*271STOP,
      BCHE*500STOP, BCHE*FS6, and BCHE*I2E3-8G, encode BChES truncated at their C
      terminus because of premature stop codons caused by nucleotide substitutions, a
      frame shift, or altered splicing. The large number of different silent BCHE
      alleles found within a relatively small number of patients shows that the
      heterogeneity of the silent BChE phenotype is high. The characterization of
      silent BChE variants will be useful in the study of the structure/function
      relationship for this and other closely related enzymes.

PMID- 8554069
TI  - Analysis of a splice-site mutation in the sap-precursor gene of a patient with
      metachromatic leukodystrophy.
AB  - Sphingolipid activator proteins (SAPs) are small, nonenzymatic glycoproteins
      required for the lysosomal degradation of various sphingolipids with a short
      oligosaccharide chain by their exohydrolases. Four of the five known activator
      proteins (sap-A-sap-D), also called "saposins," are derived from a common
      precursor by proteolytic processing. sap-B stimulates hydrolysis of sulfatides by
      arylsulfatase A in vivo. Its recessively inherited deficiency results in a
      metabolic disorder similar to classical metachromatic leukodystrophy, which is
      caused by a defect of arylsulfatase A. Here we report on a patient with sap-B
      deficiency. Reverse-transcription-PCR studies on the patient's mRNA revealed the
      occurrence of two distinct mutant species: one with an in-frame deletion of the
      first 21 bases of exon 6, the other with a complete in-frame deletion of this
      exon. The patient was homozygous for the underlying mutation, which was found to
      be a G-->T transversion within the acceptor splice site between intron e and exon
      6, abolishing normal RNA splicing. Allele-specific oligonucleotide hybridization
      revealed that the parents and both grandfathers of the patient were carriers of
      this mutation. In order to analyze the fate of the mutant precursor proteins,
      both abnormal cDNAs were stably expressed in baby hamster kidney cells. Pulse
      chase experiments showed that the deletion of 21 bp had no effect on the
      transport and the maturation of the encoded precursor. All sap forms except sap-B
      were detectable by immunochemical methods. The cDNA bearing a complete deletion
      of exon 6 encoded a shortened precursor of only 60 kD, and no mature SAPs were
      detectable. The carbohydrate chains of this polypeptide were of the high-mannose
      and hybrid type, indicating no transport of the mutant precursor beyond early
      Golgi apparatus. An endoplasmic-reticulum localization of this polypeptide was
      supported by indirect immunofluorescence analysis.

PMID- 8554070
TI  - Absence makes the search grow longer.

PMID- 8554071
TI  - Molecular genetic defect underlying alpha-L-iduronidase pseudodeficiency.
AB  - Mucopolysaccharidosis type I (i.e., Hurler, Hurler-Scheie, and Scheie syndromes)
      and type II (i.e., Hunter syndrome) are lysosomal storage disorders resulting
      from alpha-L-iduronidase (IDUA) deficiency and iduronate-2-sulfatase (IDS)
      deficiency, respectively. The a priori probability that both disorders would
      occur in a single individual is approximately 1 in 5 billion. Nevertheless, such
      a proband was referred for whom clinical findings (i.e., a male with
      characteristic facies, dysostosis multiplex, and mental retardation) and
      biochemical tests indicated these concomitant diagnoses. In repeated studies,
      leukocyte 4 methylumbelliferyl-alpha-L-iduronidase activities in this kindred
      were as follows: <1.0 nmol/mg protein/h in the proband and proband's clinically
      normal sister; 45.3 in mother; and 45.7 in father (normal range 65.0-140).
      Leukocyte L-O-(alpha-iduronate-2-sulfate)-(1->4)-D-O-2,5-anhydro[1-3H]mannitol-6-
      sulfate activities were as follows: 0.0 U/mg protein/h in the proband; 5.7 in his
      sister; 4.9 in mother; and 15.0 in father (normal range 11.0-18.4). Multiple
      techniques, including automated sequencing of the entire IDS and IDUA coding
      regions, were employed to unravel the molecular genetic basis of these intriguing
      observations. The common IDS mutation R468W was identified in the proband, his
      mother, and his sister, thus explaining their biochemical phenotypes.
      Additionally, the proband, his sister, and his father were found to be
      heterozygous for a common IDUA mutation, W402X. Notably, a new IDUA mutation
      A300T was also identified in the proband, his sister, and his mother, accounting
      for reduced IDUA activity in these individuals; the asymptomatic sister, whose
      cells demonstrated normal glycosaminoglycan metabolism, is thus a compound
      heterozygote for W402X and the new allele. This A300T mutation is the first IDUA
      pseudodeficiency gene to be elucidated at the molecular level.

PMID- 8554072
TI  - Screening the 3' region of the polycystic kidney disease 1 (PKD1) gene reveals
      six novel mutations.
AB  - Recently, the gene for the most common form of autosomal dominant polycystic
      kidney disease (ADPKD), PKD1 (polycystic kidney disease 1), has been fully
      characterized and shown to encode an integral membrane protein, polycystin,
      involved in cell-cell and/or cell-matrix interactions. Study of the PKD1 gene has
      been complicated because most of the gene lies in a genomic region reiterated
      several times elsewhere on the same chromosome, and consequently only seven
      mutations have been described so far. Here we report a systematic screen covering
      approximately 80% of the approximately 2.75 kb of translated transcript that is
      encoded by single-copy DNA. We have identified and characterized six novel
      mutations that, together with the previously described changes, amount to a
      detection rate of 10%-15% in the population studied. The newly described
      mutations are two deletions, an insertion of a T-nucleotide causing a frame
      shift, two single-base-pair substitutions resulting in premature stop codons, and
      a G-->C transversion that may be a missense mutation. These results have
      important implications for genetic diagnosis of PKD1 because they indicate that
      the majority of mutations lie within the duplicated area, which is difficult to
      study. The regions of polycystin removed in each mutation so far described are
      assessed for their functional significance; an area disrupted by two new small in
      frame changes is highlighted. PKD1 mutations are contrasted with those in the
      PKD1/TSC2 contiguous-gene syndrome, and the likely mutational mechanism in PKD1
      is considered.

PMID- 8554074
TI  - Clinical study of a large family with autosomal dominant progressive cone
      degeneration.
AB  - PURPOSE: Autosomal dominant cone degeneration is an uncommon disorder
      characterized by progressive photophobia, hemeralopia, decreased central vision,
      and dyschromatopsia. To better understand the variable expressivity of autosomal
      dominant cone degeneration, we studied a single, large family. METHODS: We
      performed comprehensive ophthalmic examinations, full-field electroretinography,
      foveal electroretinography, and color vision studies on 73 family members.
      RESULTS: Of the 73 family members, 34 were affected. Symptoms generally began in
      the first decade of life and slowly progressed into midlife. Ophthalmoscopic
      findings consisted primarily of macular granularity or central macular atrophy.
      The photopic full-field electroretinogram was important in establishing the
      diagnosis, although the results of the electroretinographic measurements varied
      across individuals. Either the foveal electroretinogram amplitudes were
      abnormally low or the foveal/parafoveal ratio was abnormal in all affected
      subjects. CONCLUSIONS: No single test or finding was completely sensitive or
      specific for accurate diagnosis of autosomal dominant cone degeneration.
      Especially in the more mildly affected subjects, a constellation of symptoms,
      findings, and test results were used to diagnose autosomal dominant cone
      degeneration accurately.

PMID- 8554075
TI  - Echographic evaluation of primary cysts of the iris pigment epithelium.

PMID- 8554073
TI  - Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD)
      deficiency: identification and characterization of mutant VLCAD cDNAs from four
      patients.
AB  - Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency is a newly
      identified disease. A 105-bp deletion in the VLCAD cDNA in two patients has been
      reported, and detailed molecular characterization of this disease has remained to
      be done. We report here five mutations identified in four patients: a 135-bp
      deletion encompassing bases 343-477, a C-1837-to-T transition (R613W), 3-bp
      deletions at the nucleotide positions 388-390 (E130del) and 895-897 (K299del),
      and an A-1144-to-C transversion (K382Q). Sequencing of genomic DNA amplified by
      PCR revealed a 135-bp deletion caused by exon skipping due to a 1-bp deletion in
      a 3' splice site of an intron. In cDNA expression experiments using Chinese
      hamster ovary (CHO) cells, we found that each of the mRNAs derived from E130del
      and K299del clones were unstable and that translation products from R613W,
      E130del, K299del, and K382Q clones were labile. Each of R613W, E130del, K299del,
      and K382Q proteins expressed in CHO cells appeared abnormal in dimer assembly, as
      shown in gel-filtration analysis. VLCAD activity was not detected in mutants'
      transfectants. Thus, we verified that all five mutations identified in these four
      patients were disease-causing alterations.

PMID- 8554076
TI  - Mapping of autosomal dominant cone degeneration to chromosome 17p.
AB  - PURPOSE: We studied a single, large family with autosomal dominant cone
      degeneration in order to map the disease-causing gene. METHODS: Seventy-three
      individuals in this family were examined, and 34 were found to be affected. Blood
      samples from 34 affected and unaffected family members were obtained for DNA
      analysis and linkage mapping. Fifty-three genetic markers were analyzed in this
      family by using short tandem repeat markers. These markers were primarily in
      candidate genomic regions. RESULTS: Marker D17S796 generated a significantly
      positive LOD score of 4.21 (theta = .04; 10,000:1 odds in favor of linkage).
      Marker D17S513 gave a significant LOD score of 3.1 (theta = .096; 1,000:1 odds in
      favor of linkage). Other markers in the region generated suggestive findings,
      such as D17S786, with a LOD score of 2.7, and D17S945, with a LOD score of 2.41.
      CONCLUSIONS: Our results indicate that a genetic defect that causes autosomal
      dominant cone degeneration is located on chromosome 17p in the region of
      recoverin. Recoverin, a retinal expressed gene, is an appealing candidate for
      this disease.

PMID- 8554077
TI  - Retinitis punctata albescens associated with the Arg135Trp mutation in the
      rhodopsin gene.
AB  - PURPOSE: To screen for mutations in the rhodopsin, peripherin/RDS, and ROM1 genes
      in a family affected with retinitis punctata albescens. Because clinical
      heterogeneity was observed in this family, with some members affected with
      retinitis punctata albescens and one member affected with features typical of
      retinitis pigmentosa, we analyzed the apolipoprotein E gene to elucidate this
      unusual intrafamilial heterogeneity. METHODS: The coding sequences of these genes
      were analyzed with a combination of single-strand conformation polymorphism and
      direct sequence analysis. Haplotypes of the apolipoprotein E gene were analyzed
      by polymerase chain reaction and enzymatic digestion. RESULTS: The Arg135Trp
      mutation in the rhodopsin gene was observed in all affected members of this
      family, but no mutation was detected in the peripherin/RDS or ROM1 genes. The e4
      allele of the apolipoprotein E gene apparently cosegregated with the albescens
      phenotype in this family. CONCLUSIONS: The albescent phenotype in retinal
      dystrophy appears to not be caused exclusively by a peripherin/RDS gene mutation,
      and we suggest that the apolipoprotein E gene may play a role in the albescent
      phenotype.

PMID- 8554078
TI  - Choroidal capillary and venous congestion in central serous chorioretinopathy.
AB  - PURPOSE: Abnormalities in choroidal perfusion have been hypothesized to be
      causative factors in central serous chorioretinopathy. This prospective study was
      performed to evaluate changes in the choroidal circulation in cases of central
      serous chorioretinopathy. METHODS: In 32 consecutive patients with acute or
      chronic recurrent central serous chorioretinopathy, complete clinical
      ophthalmologic examinations, fluorescein angiography, and indocyanine green
      angiography with a scanning laser ophthalmoscope and a digital imaging system
      were performed. RESULTS: All patients with acute and chronic recurrent central
      serous chorioretinopathy demonstrated a localized delay in arterial filling
      followed by choroidal hyperperfusion in the area of the damaged retinal pigment
      epithelium, frequently associated with dilated capillaries and dilated draining
      venules in one or more choroidal lobules. These changes corresponded to areas
      with pigment epithelial detachment or focal leakage from the retinal pigment
      epithelium found in fluorescein angiography. Furthermore, in some patients,
      localized choroidal ischemia could be observed in additional areas throughout the
      central fundus in both diseased eyes and normal fellow eyes. CONCLUSIONS: Delayed
      arterial filling followed by capillary and venous hyperemia, angiographically
      appearing as capillary and venous congestion, can be observed frequently in eyes
      with central serous chorioretinopathy. The results suggested that capillary or
      venous congestion after ischemia in one or more choroidal lobules might be the
      reason for the choroidal hyperpermeability associated with central serous
      chorioretinopathy.

PMID- 8554079
TI  - Causes of uveitis in the general practice of ophthalmology. UCLA Community-Based
      Uveitis Study Group.
AB  - PURPOSE: Most uveitis case series have come from tertiary care centers, and the
      relative frequencies of disorders they report may reflect referral bias. We
      sought information about the types of uveitis encountered in the general practice
      of ophthalmology. METHODS: We prospectively examined 213 consecutive cases of
      general uveitis, defined as intraocular inflammation other than cytomegalovirus
      retinopathy, seen by a group of community-based comprehensive ophthalmologists.
      This group of cases was compared with 213 consecutive cases of general uveitis
      examined by a uveitis specialist at a university referral center in the same
      community. All cases were categorized by anatomic site of inflammation and
      disease course, and, if possible, they were assigned a specific diagnosis. Cases
      of cytomegalovirus retinopathy and masquerade syndrome seen during the same
      intervals were recorded separately. RESULTS: The distribution of general uveitis
      cases by anatomic site of disease was significantly different between the
      community-based practices (anterior, 90.6%; intermediate, 1.4%; posterior 4.7%;
      panuveitis, 1.4%) and the university referral practice (anterior, 60.6%;
      intermediate, 12.2%; posterior, 14.6%; panuveitis, 9.4%; P < .00005). A cause or
      clinical syndrome could be assigned to 47.4% of cases in the community-based
      practices, and to 57.8% of cases in the university referral practice (P = .03).
      HLA-B27-associated anterior uveitis, cytomegalovirus retinopathy, and toxoplasmic
      retinochoroiditis were among the five most common forms of uveitis in both
      practice settings. CONCLUSION: The relative frequencies with which various forms
      of uveitis are seen in a tertiary referral center do not necessarily reflect the
      experience of ophthalmologists from the community in which the center is located.
      Anterior uveitis and disorders of sudden onset constitute a greater proportion of
      cases seen by community-based comprehensive ophthalmologists.

PMID- 8554080
TI  - Clinical features and associated systemic diseases of HLA-B27 uveitis.
AB  - PURPOSE: To delineate the clinical features, course, complications, and
      associated systemic diseases in patients with HLA-B27-associated uveitis.
      METHODS: We reviewed the records of 148 patients with HLA-B27-associated uveitis
      from two large uveitis practices. RESULTS: There were 127 (86%) white and 21
      (14%) nonwhite patients, and a male-to-female ratio of 1.5:1. The median age at
      onset of uveitis was 32 years; eight patients (5%) had their first attack after
      age 55 years. Acute anterior uveitis was noted in 129 patients (87%), and
      nonacute inflammation was noted in 19 (13%). Ocular involvement was categorized
      as unilateral or unilateral alternating in 138 patients (93%), but ten patients
      (7%) had bilateral, concurrent disease. The median duration of an attack was six
      weeks, and the median number of recurrences for patients with more than 12 months
      of follow-up was three. Cataracts were associated with posterior synechiae (P =
      .03), increased intraocular pressure (P = .003), and cystoid macular edema (P =
      .04). An HLA-B27-associated systemic disorder was present in 83 patients (58%),
      30 of whom were women, and it was diagnosed in 43 of the 83 patients as a result
      of the ophthalmologic consultation. Thirty-four (30%) of 112 patients had a
      family history of a spondyloarthropathy. CONCLUSIONS: Although HLA-B27-associated
      uveitis is usually described as a disease of young white men, women and nonwhites
      may also be affected. A subgroup of patients have severe disease and consequently
      more complications. Most patients have an associated systemic disease, including
      women, who appear to have more atypical spondyloarthropathies. The systemic
      diseases were frequently undiagnosed before the onset of the ocular disease and
      before the uveitis consultation.

PMID- 8554081
TI  - Corneal astigmatism after phacoemulsification and lens implantation through
      unsutured scleral and corneal tunnel incisions.
AB  - PURPOSE: We compared the changes in corneal astigmatism after phacoemulsification
      and intraocular lens implantation in 93 consecutive eyes with unsutured 4-mm
      superior scleral tunnel incisions to those through 105 consecutive eyes with
      unsutured 3.2- to 3.5-mm temporal corneal tunnel incisions. METHODS: Keratometry
      measurements were obtained preoperatively and at postoperative day 1, week 1, and
      week 6. Group differences in scalar and vector astigmatism were compared by using
      analysis of variance methods. RESULTS: Mean scalar astigmatism in the scleral
      incision group changed from preoperative astigmatism by 0.65 diopter at
      postoperative day 1, 0.37 diopter at postoperative week 1, and 0.13 diopter at
      postoperative week 6. Mean scalar astigmatism in the corneal incision group
      changed from preoperative astigmatism by 0.39 diopter at postoperative
      astigmatism by 0.39 diopter at postoperative day 1, 0.21 diopter at postoperative
      week 1, and 0.13 diopter at postoperative week 6. Mean vector astigmatism in the
      scleral incision group changed 1.26 diopters at 80 degrees at postoperative day
      1, 1.05 diopters at 83 degrees at postoperative week 1, and 0.42 diopter at 103
      degrees at postoperative week 6. Mean vector astigmatism in the corneal incision
      group changed 0.77 diopter at 90 degrees at postoperative week 1, and 0.61
      diopter at 89 degrees at postoperative week 6. The differences were statistically
      significant (P = .003) only by vector analysis at the postoperative day 1
      examination. CONCLUSIONS: We found significantly greater with-the-rule change in
      astigmatism in the scleral incision group than in the corneal incision group on
      the first postoperative day. The effect disappeared by the sixth postoperative
      week.

PMID- 8554082
TI  - Analysis of astigmatic keratotomy with a 5.0-mm optical clear zone.
AB  - PURPOSE: To investigate the surgically induced refractive change after astigmatic
      keratotomy with a 5.0-mm optical clear zone in patients with severe naturally
      occurring astigmatism. METHODS: We analyzed surgically induced refractive change
      in 40 consecutive eyes undergoing astigmatic keratotomy with a 5.0-mm optical
      clear zone. The surgically induced refractive change was calculated according to
      the method of Holladay, Cravy, and Koch with some modifications. Eyes were
      divided into two groups: Group I included eyes with mixed astigmatism and a
      maximum preoperative spherical equivalent of +1.25 diopters that underwent
      arcuate keratotomy, and Group II included eyes with compound myopic or simple
      myopic astigmatism (maximum preoperative spherical equivalent of -3.00 diopters)
      or mixed astigmatism with low minus spherical equivalent that underwent four
      incision radial keratotomy and arcuate keratotomy. RESULTS: After refractive
      surgery, all eyes experienced a reduction of astigmatism when examined three
      months or more after surgery. Only one eye from each group was overcorrected. The
      magnitude of refractive astigmatism of surgically induced refractive change was
      3.25 +/- 0.90 diopters for eyes in Group I and 3.25 +/- 0.80 diopters for eyes in
      Group II. There was minimal axis deviation. Eyes in Group I had more flattening
      with the wound than steepening against the wound, with a coupling ratio of -0.86
      +/- 0.36, whereas in Group II, there was flattening both with the wound and
      against the wound. The net effect of surgery (sum of the primary and secondary
      effects) was more flattening than steepening in Group I eyes, and flattening of
      the circumference of the eye in Group II. A decrease of one line of best
      corrected visual acuity was observed in one (6.6%) of 15 eyes in Group I and in
      two (8%) of 25 eyes in Group II. CONCLUSIONS: A 5.0-mm optical clear zone arcuate
      keratotomy is an effective method for correcting moderate to severe naturally
      occurring astigmatism. Further investigation of this optical clear zone size on
      glare and contrast sensitivity testing is necessary and is underway.

PMID- 8554083
TI  - Effect of levodopa and carbidopa on recovery of visual function in patients with
      nonarteritic anterior ischemic optic neuropathy of longer than six months'
      duration.
AB  - PURPOSE: We conducted a pilot clinical trial to determine the efficacy of
      levodopa in promoting visual recovery in eyes with nonarteritic anterior ischemic
      optic neuropathy of greater than six months' duration. METHODS: This prospective,
      randomized, double-masked, placebo-controlled clinical trial involved 20 subjects
      with nonarteritic anterior ischemic optic neuropathy of 30 months' mean duration.
      Subjects were randomly assigned to receive either low-dose levodopa and carbidopa
      or a placebo for three weeks. At 12 weeks after the baseline visit, the levodopa
      group then was provided a higher, conventional dose of levodopa and carbidopa for
      three more weeks. Change in visual function was monitored at four, 12, 16, and 24
      weeks after the baseline visit. RESULTS: At 12 weeks after the baseline visit,
      the levodopa group experienced a significant (P = .016) mean difference in
      improvement of visual acuity of 5.9 letters from the placebo group. At 24 weeks
      after the baseline visit, a significant treatment effect (P = .036) for visual
      acuity was still evident; the levodopa group had a mean gain in improvement of
      7.5 letters difference from baseline from the placebo group. Three subjects in
      the levodopa group experienced a doubling of the visual angle as denoted by a
      gain of at least 15 letters. Significant improvement was not observed for color
      vision (P = .82) or mean deviation of visual field loss (P = .82). CONCLUSION:
      The study found significant improvement of visual acuity among subjects receiving
      levodopa and carbidopa despite long-standing visual loss from nonarteritic
      anterior ischemic neuropathy. Confirmation of our results is awaited from larger
      population studies and with a longer follow-up time interval regarding the
      efficacy of levodopa in reversing visual loss in this disease.

PMID- 8554084
TI  - Corneal endothelial changes in schizophrenic patients with long-term
      administration of major tranquilizers.
AB  - PURPOSE: To examine corneal endothelial changes in schizophrenic patients who
      underwent long-term administration of major tranquilizers. METHODS: We performed
      slit-lamp examination and endothelial specular microscopy on 100 eyes of 50
      schizophrenic patients (range, 31 to 68 years old; mean, 54 years) who underwent
      long-term (12 to 44 years) treatment with major tranquilizers. We also studied 50
      eyes of 25 patients (range, 31 to 65 years old; mean, 53 years) with no history
      of corneal disease, as a control group of similar age. Mean cell density,
      coefficient of variation, and percentage of hexagonal cells were calculated and
      statistically compared between patients and controls using an unpaired t-test.
      RESULTS: Slit-lamp examination disclosed pigmentation of the cornea in nine eyes
      of five patients and pigmentation of the lens in 25 eyes (25%) of 35 patients.
      Corneal pigmentary changes were seen only in patients with lenticular changes. No
      eyes showed corneal edema. In contrast, no corneal abnormalities were seen in any
      control eye. Specular microscopic analysis showed mean cell density of 3,484.4 +/
      462.6 cells/mm2, coefficient of variation of 0.31 +/- 0.06 and percentage of
      hexagonal cells to be 60.2% +/- 7.5% in the patient group, and 3,291.3 +/- 384.4
      cells/mm2, 0.32 +/- 0.07, and 60.6% +/- 7.0%, respectively, in the control
      subjects. There were no statistically significant differences between patient and
      control eyes in these three factors. The nine eyes with corneal pigmentation
      showed no significant differences in these three factors as compared with the
      control subjects. CONCLUSIONS: These results indicate that long-term treatment
      with major tranquilizers is not associated with morphometric abnormalities of the
      corneal endothelium.

PMID- 8554085
TI  - Diagnosis of microsporidial keratitis by confocal microscopy and the chromatrope
      stain.
AB  - PURPOSE: To illustrate the value of confocal microscopy and chromatrope stain in
      the diagnosis of microsporidial keratitis. METHODS: In vivo confocal microscopy
      was performed on a man with the human immunodeficiency virus who had severe
      bilateral epithelial keratitis refractory to topical antibacterial medications.
      The results were compared to conjunctival scrapings stained with the chromatrope
      based Weber stain. RESULTS: Confocal microscopy demonstrated many small,
      intraepithelial opacities of the corneal epithelium, which were suggestive of
      Microsporidia. Results of the chromatrope stain of conjunctival scrapings
      confirmed the diagnosis of microsporidial keratitis. CONCLUSIONS: Rapid diagnosis
      allowed prompt initiation of topical fumagillin, which permitted rapid, long-term
      control of the symptoms of microsporidial keratitis.

PMID- 8554086
TI  - Cystic hydrops and spontaneous perforation in Fuchs' superficial marginal
      keratitis.
AB  - PURPOSE: We studied a case of Fuchs' superficial marginal keratitis in which
      cystic corneal hydrops developed in one eye, and spontaneous corneal perforation
      occurred in the fellow eye. METHODS: The patient underwent bilateral annular
      corneoscleral lamellar patch grafts for tectonic support. RESULTS: The patient
      had an uncomplicated postoperative course and visual acuity of 20/25 bilaterally.
      CONCLUSION: Stromal loss in Fuchs' superficial marginal keratitis may be severe
      enough to result in cystic corneal hydrops. Patients with this disorder should be
      counseled regarding the possibility of corneal perforation.

PMID- 8554087
TI  - Annular keratotomy for the treatment of painful bullous keratopathy.
AB  - PURPOSE: To determine whether annular keratotomy can relieve pain associated with
      bullous keratopathy. METHODS: Three patients with painful bullous keratopathy and
      poor visual potential underwent partial-thickness (0.30 to 0.42 mm) trephination
      of the cornea under local anesthesia. RESULTS: All patients reported an absence
      of pain and foreign body sensation during an average follow-up interval of six
      months. The surgical procedure was uncomplicated; however, two eyes developed
      increased central corneal stromal edema. CONCLUSIONS: Annular keratotomy appears
      to be a relatively safe and simple surgical procedure that may be useful in
      managing pain in eyes with painful cornea edema and poor visual potential.

PMID- 8554088
TI  - Squamous cell carcinoma of the conjunctiva in a patient with the acquired
      immunodeficiency syndrome.
AB  - PURPOSE: To alert ophthalmologists to the possibility of human immunodeficiency
      virus (HIV) infection in individuals with conjunctival squamous cell carcinoma.
      METHODS: We treated a 24-year-old patient with the acquired immunodeficiency
      syndrome who developed a limbal mass. The mass was excised and examined by
      routine histologic and immunohistochemical methods. RESULTS: The histopathologic
      examination disclosed infiltrating squamous cell carcinoma with features of
      spindle cell carcinoma. Frequent abnormal mitotic figures were present in this
      neoplasia. CONCLUSIONS: Squamous cell carcinoma with histologic features of
      aggressive behavior in a young individual should alert physicians to the
      possibility of HIV infection. Such patients may require frequent follow-up
      examination, even after complete excision of the tumor.

PMID- 8554089
TI  - Treatment of migraine headache after ocular surgery with intravenous
      metoclopramide hydrochloride.
AB  - PURPOSE: To alert ophthalmologists that prolonged or severe postoperative
      periocular pain and nausea may be caused by migraine. METHODS: We examined two
      patients who had a history of migraine and had severe episodes of prolonged
      periocular pain and nausea after ocular procedures. Both patients experienced
      symptoms similar to their previous migraine attacks. In neither was pain
      alleviated by routine analgesics. RESULTS: Each patient had relief of symptoms
      within two minutes after intravenous delivery of metoclopramide hydrochloride.
      CONCLUSIONS: Ophthalmologists should consider the diagnosis of postoperative
      migraine in similar patients and provide specific therapy such as intravenous
      metoclopramide hydrochloride.

PMID- 8554090
TI  - Ocular manifestation of hairy cell leukemia with dramatic response to 2-chloro
      deoxy-adenosine.
AB  - PURPOSE: To demonstrate that hairy cell leukemia may involve the eye. METHODS: We
      examined a patient who had a unique ocular manifestation of hairy cell leukemia
      with severe panuveitis in one eye and leukemic retinopathy in the fellow eye.
      RESULTS: Therapy with 2-chloro-deoxy-adenosine, a drug recently introduced for
      treatment of hairy cell leukemia, led to dramatic improvement of the ocular
      complications. CONCLUSIONS: Hairy cell leukemia may involve the eye and ocular
      symptoms may respond to systemic treatment with 2-chloro-deoxy-adenosine.

PMID- 8554091
TI  - Evidence-based education?

PMID- 8554092
TI  - Hearts, lungs, and children: a physiologist returns to kindergarten.
AB  - Scientific illiteracy is a prevalent problem: between kindergarten and high
      school, most children progressively lose their inherent affinity for science
      exploration. The correction of this deficiency requires vigorous participation by
      the scientific community. This paper details my experiences introducing
      kindergartners to the basics of cardiorespiratory physiology: pulmonary
      ventilation and circulatory transport of oxygen. More important, my presentation
      gives children an opportunity to participate in the process of scientific inquiry
      and to discover and explore the mystique of real hearts and lungs. The children
      and their teachers truly enjoy the demonstration. In particular, my use of animal
      organs meets with phenomenal success: the children are enchanted by my inflation
      and their exploration of pig lungs, and one teacher told me weeks afterward that
      her students were still "bragging of how they touched a real heart and lung."
      Young children delight in science exploration and marvel at the wonder inherent
      to physiology. Armed with an intriguing hands-on presentation and a spirit of
      adventure and fun, any scientist can return to kindergarten. The rewards are
      likely to be profound.

PMID- 8554093
TI  - Resting membrane potentials: a student test of alternate hypotheses.
AB  - The frog sartorius muscle is a model tissue for demonstrating to physiology
      students the principles underlying both membrane phenomena and hypothesis
      testing. Myocytes can be impaled with conventional glass microelectrodes to
      measure membrane voltage (Vm). Further, Vm is observed as extracellular K+ is
      altered and a K+ channel blocker is added. After the experiment, students examine
      the underlying assumptions of the Nernst equilibrium and the Goldman-Hodgkin-Katz
      equation. They ultimately determine which of the two algorithms best predicts the
      measured Vm. In addition, students learn micromanipulation and impalement
      techniques. This experiment facilitates the student's understanding of membrane
      permeability, ionic gradients, and membrane voltage.

PMID- 8554094
TI  - An educational tool for understanding the cardiovascular changes associated with
      diabetes.
AB  - Diabetes, a syndrome characterized by high plasma glucose and low plasma insulin
      concentrations, is associated with somatic and autonomic neuropadiabetes as well
      as cardiac and vascular disorders. These consequences of diabetes significantly
      affect the organism's ability to maintain homeostasis. To understand the changes
      associated with diabetes, we developed a laboratory exercise that compares and
      contrasts the cardiovascular responses to exercise in an individual with diabetes
      and in an individual without diabetes. This exercise provides a unique
      opportunity to analyze, integrate, and interpret the changes associated with
      diabetes, since more is learned about how a system operated when the system is
      forced to perform than when it is idle. In this laboratory, anatomical and
      physiological data concerning diabetes are provided. Subsequently, a figure that
      illustrates the response of a specific cardiovascular variable during exercise
      (e.g., heart rate, cardiac output, blood pressure) is presented. Students are
      challenged to analyze and assimilate information from figures, answer questions,
      make calculations, fill in tables, and plot graphs. The laboratory does not
      require equipment or software, only rulers and pencils. The answers to the
      questions and tables are provided in the APPENDIX. Students obtain experience in
      evaluating and understanding diabetes as well as applying basic cardiovascular
      concepts. The emphasis is on the application of basic cardiovascular principles,
      interpretation of pictorial or tabular material, and problem-solving skills.

PMID- 8554095
TI  - Investigative approach to frog gastrocnemius laboratory: potential impact on
      animal use in teaching laboratories.
AB  - With growing concern over the use of animal experimentation in the teaching of
      physiology, many biology departments are reassessing the use of animal
      experiments in the teaching lab. However, it may be just as important to assess
      how animal experimentation is used in the undergraduate teaching laboratory
      rather than simply assessing if animal experimentation should be used at all. In
      our study, sophomore-level life science students enrolled in a core organismal
      biology course undertook a laboratory exercise designed to elucidate properties
      of muscles and neuromuscular communication following two protocols: 1) a standard
      demonstrational model wherein students were told to undertake the exercise as a
      means to understand physiological processes that they had been exposed to
      previously in lecture or 2) an investigative model wherein the use of the
      gastrocnemius preparation was a logical next step in an ongoing investigation,
      the content of which was driven by student-generated hypotheses. We have observed
      a significant decrease in a number of the negative comments concerning the use of
      animals in experimentation (25.6 vs. 3.6%) since the implementation of the
      investigative approach to the laboratory, suggesting that curricular approaches
      to the use of animals in the teaching laboratory may have an impact on student
      attitudes concerning animal experimentation.

PMID- 8554096
TI  - Understanding physiology by acting out concepts.
AB  - Typically, classes in anatomy and physiology are taught via lecture and visual
      aids. This seems to work well for students who are primarily auditory and visual
      learners but not for those who learn better through kinesthetic experiences. This
      is the first report describing the use of improvisation to act out physiological
      concepts within an anatomy and physiology course. Improvisational techniques
      encourage active participation and allow students to personally interact with and
      experience difficult concepts in the classroom. In this paper, sensory modality
      preferences for learning will be discussed briefly. Improvisational techniques
      will be described, and examples of improvisations useful to convey intricate
      physiological concepts will be provided. Last, student responses to the use of
      improvisational techniques in an anatomy and physiology course will be reported.

PMID- 8554097
TI  - Integrative physiology: some texts and methods of integrative study.
AB  - The development of the integrative dimensions of physiology will require texts
      and forms of study that differ from those to which we have become accustomed in
      the areas of specialization. The following two types of texts lie at the heart of
      integrative study: framework statements and case histories. Framework statements
      are scientific aphorisms that summarize integrative insights; ordered chains of
      these statements form conceptual frameworks that stimulate integrative dialogue
      and thought. Case histories are stories that portray the events in the life of a
      living being, generally human. The nature of these texts, how framework
      statements are created, and methods of how texts of this kind may be used in
      group dialogues are discussed.

PMID- 8554098
TI  - Starting a neuroscience research laboratory in a developing country: a Fulbright
      experience in Honduras.
AB  - The first laboratory of neurophysiology was installed in the medical school of
      the University of Honduras during the 1992-1993 academic year. The goal of the
      project was to improve the teaching of physiology in the medical curriculum and
      to establish a neuroscience research laboratory able to address Honduran needs.
      In addition to a computer learning facility and wet labs in neurophysiology for
      medical students, an independent research program that focused on social problems
      in the country (for example, the effects of malnutrition on the developing
      central nervous system) was developed, paving the way for the first graduate
      program in physiology in Honduras. Funded by a Fulbright Lectureship Grant, the
      shoe-string budget was augmented by donations of equipment by colleagues. This
      first-hand account describes the planning and implementation of the project,
      covering both expected and unexpected problems and successes. An update on the
      progress of the lab after two years of independent operation is also described.

PMID- 8554099
TI  - Teaching in an offshore Caribbean medical school.

PMID- 8554100
TI  - Active learning in large class settings.
AB  - Science education is in the process of shifting from the mastery of a large body
      of factual information to an emphasis on the development of reasoning skills and
      the solving of practical problems. Such skills are best developed by instructors
      and students working together in an active learning environment as opposed to
      instructors and students being, respectively, sources and sinks of factual
      knowledge. Most models of active learning are geared toward small group (< 15
      students) settings in which interactions between students and instructor are
      optimized. However, basic courses in physiology are often forced to meet in large
      classes in which it is more difficult to utilize active learning methods. The
      panelists in this workshop demonstrated techniques that they use in large class
      settings to promote an active learning experience. We hope that this summary of
      the workshop will encourage you to experiment with educational approaches to
      improve the efficacy of teaching in the large class setting.

PMID- 8554101
TI  - Conference on teaching physiology.

PMID- 8554102
TI  - Pleomorphic soft tissue myogenic sarcomas of adulthood. A reappraisal in the mid
      1990s.
AB  - 325 diverse sarcomas, 39 rhabdomyosarcomas (RMS), including all histologic
      variants, and 135 leiomyosarcomas (LMS) were identified. Within these two groups,
      18 (46%) of the RMS and 14 (10%) of the LMS represented pleomorphic variants.
      These neoplasms were studied by morphology (histology and ultrastructure) and by
      immunohistochemical methods employing antibodies to intermediate filaments
      (vimentin and desmin) and actin isoforms [alpha-smooth (sm) and alpha-sarcomeric
      (sr) actins]. Twenty-four pleomorphic malignant fibrous histiocytomas (MFH) and
      eight pleomorphic liposarcomas (LS) were examined in a similar fashion. By light
      microscopy, the pleomorphic RMS, LMS, and MFH were indistinguishable, as each was
      dominated by pleomorphic cells disposed in a haphazard growth pattern; moreover,
      many featured fascicular, storiform, and sclerotic zones. The distinction between
      these neoplasms became apparent only following immunohistochemistry and/or
      ultrastructural study. All pleomorphic RMS disclosed rudimentary sarcomeres and
      exhibited the following cytoskeletal profile: vimentin (+) (18 of 18), desmin (+)
      (14 of 18), alpha-sr actin (+) (18 of 18) and alpha-sm actin (+) (five of 18).
      All the pleomorphic LMS featured smooth-muscle differentiation of variable
      degrees in the form of cytoplasmic bundles of microfilaments and associated dense
      bodies; their cytoskeletal profile was vimentin (+) (14 of 14), desmin (+) (seven
      of 14), alpha-sr actin (+) (none of 14), and alpha-sm actin (+) (eight of 14).
      The latter was demonstrated in all moderately differentiated, but absent or only
      focally expressed in poorly differentiated variants. All pleomorphic MFH and LS
      were devoid of myogenic (skeletal or smooth) ultrastructural features and
      expressed vimentin solely. This combined morphological and immunohistochemical
      study illustrates the following: First, these pleomorphic sarcomas are often
      indistinguishable by histologic growth pattern alone; thus, an accurate diagnosis
      requires study with all of these techniques. Second, pleomorphic myogenic
      sarcomas are restricted to adults and are not uncommon neoplasms among
      pleomorphic sarcomas: RMS (28%), LMS (21%), MFH (38%), and LS (13%). Third, the
      study defines desmin-negative and alpha-sm actin-positive pleomorphic RMS, and
      desmin-negative and alpha-sm-actin-negative pleomorphic LMS.

PMID- 8554103
TI  - Soft tissue gliomatosis. Morphologic unity and histogenetic diversity.
AB  - Normal-appearing tissues in non-native sites constitute one of the more common
      morphologic expressions of abnormal development. The presence of pancreas in the
      wall or on the serosa of the small intestine and adrenal cortical tissue in a
      hernia sac are two familiar examples of heterotopias. We report our experience of
      mature glial tissues in the soft tissues of six children who were between the
      ages of 4.5 months and 2 years when they presented with a solitary mass on the
      chest wall (three cases), scalp (two cases) and gluteal region (one case). These
      tumors were all characterized by pale-staining fibrillary foci of mature
      neuroglia, which were intensely immunoreactive for glial fibrillary acidic
      protein in each case. One of the two scalp lesions was accompanied by a nodule of
      cartilage and a meshwork of pseudovascular spaces, which were decorated with
      antibodies to vimentin and epithelial membrane antigen consistent with
      meningothelial tissue. The histogenesis of the neuroglial tissue in the gluteal
      region and scalp was, respectively, on the basis of a recurrence of a
      sacrococcygeal teratoma in the former case and sequestered encephaloceles in the
      last two cases. A facile explanation for the occurrence of neuroglial tissue in
      the soft tissue of the chest wall in the remaining three cases was less than
      obvious as none of the patients had accompanying neurologic or anatomic defects
      and all were in a nonmidline location. These three cases of soft tissue
      gliomatosis of the chest wall are similar to an earlier example in the recent
      literature whose histogenesis was as enigmatic as it proved to be in our three
      cases. Although the histologic and immunohistochemical features of these six
      cases were very similar in each instance, their origin varied from a recurrent
      sacrococcygeal teratoma and sequestered encephaloceles to essentially unknown.

PMID- 8554104
TI  - Surface adenosquamous carcinoma of the penis. A report of three cases.
AB  - Three patients, aged 37, 72, and 74 years, with adenosquamous carcinoma of the
      penis are described. The duration of disease was 6, 9, and 144 months,
      respectively. Grossly a firm, white-gray granular exophytic mass was noted (7.6
      cm average diameter). Microscopically, a mixed carcinoma showing squamous and
      glandular elements was present; the squamous component predominated. In two cases
      the adenocarcinoma was located in the perimeatal area of the glans. The
      periurethral glands were not involved. The glandular foci were discrete and had
      minimal admixture with the squamous carcinoma. Mucin material was present in the
      lumina, apical border, and cytoplasm. Immunohistochemically, cells showed
      positivity for carcinoembryonic antigen in glandular areas. The squamous cell
      carcinomas were of the "warty" variant in two cases and of the usual squamous
      cell type in the other case. In one patient, metastatic adenosquamous carcinoma
      was noted in one inguinal node and showed mucin secretion. This patient is alive
      and well 102 months after diagnosis. Another patient is alive with no evidence of
      disease 12 months after surgery, and the third was lost to follow-up.
      Adenosquamous carcinomas of the penis are unusual neoplasms probably originating
      in penile surface epithelium and in embryologically misplaced mucus glands of the
      perimeatal region of glans mucosa.

PMID- 8554105
TI  - Sclerosing polycystic adenosis of major salivary glands. A clinicopathologic
      analysis of nine cases.
AB  - We describe nine cases of a histologically distinct and previously unreported
      lesion of the major salivary glands. The patients ranged in age from 12 to 63
      years and included four males, five females. The lesions were slow-growing masses
      in the parotid gland (eight cases) and submandibular gland (one case). The
      clinical impression in each case was a benign salivary gland tumor. Grossly, the
      lesions were discrete, pale, rubbery nodules embedded within the salivary gland
      parenchyma. Microscopically, the lesions were unencapsulated, circumscribed
      masses of sclerotic and hyalinized collagenous tissue. Irregularly distributed
      throughout the collagenous tissue in a vaguely lobular pattern were hyperplastic
      ductal and acinar elements that were usually accompanied by cystically ectatic
      ducts. The dilated ducts frequently showed apocrine-like metaplasia and
      epithelial hyperplasia, which often formed transluminal bridges in a cribriform
      pattern. This epithelial hyperplasia sometimes surrounded eosinophilic globules
      as seen in so-called collagenous spherulosis. The combination of fibrosis,
      epithelial hyperplasia, and cystic changes were reminiscent of fibrocystic
      changes of the breast. Focally, acinar elements contained large, intensely
      eosinophilic, periodic acid-Schiff's-positive, intracytoplasmic granules believed
      to represent altered zymogen granules. A sparse to focally intense lymphocytic
      infiltrate accompanied the epithelial proliferations. Previous interpretations of
      these masses have included mucoepidermoid carcinoma, low-grade adenocarcinoma,
      benign adenoma, and mixed tumor. The limited available follow-up suggests that
      this process has a favorable prognosis despite recurrences in two cases. It is
      postulated that these lesions represent a pseudoneoplastic condition that results
      in both fibrosis and epithelial proliferation. We suggest the term sclerosing
      polycystic adenosis for these rare lesions.

PMID- 8554106
TI  - Myxoid/round cell liposarcoma of the extremities. A clinicopathologic study of 29
      cases with particular attention to extent of round cell liposarcoma.
AB  - Round cell liposarcoma, a high-grade sarcoma, is a poorly differentiated form of
      myxoid liposarcoma, which is low grade. It is not known, however, how much of a
      round cell component within an otherwise typical myxoid liposarcoma results in a
      neoplasm that behaves as a high-grade sarcoma. Twenty-nine cases of myxoid
      liposarcoma of the extremities with or without a component of round cell
      liposarcoma were studied to semiquantitate the amount of round cell component
      needed to adversely affect prognosis. An estimate of the percent of necrosis,
      round cell liposarcoma, myxoid liposarcoma, and transitional areas was obtained
      for each slide on all cases. Transitional areas were defined as those that
      displayed an increased cellularity compared with typical myxoid liposarcoma, but
      in which the cells remained spindled, did not have overlapping nuclear borders,
      and retained an easily discernible plexiform vascular pattern. The amount of
      necrosis was subtracted from the total material available for evaluation, and a
      composite estimate of the percent of round cell, myxoid, and transitional areas
      was obtained. Two tumors were located on the upper extremity, 27 on the lower
      extremity; tumor size ranged frm 3 to 30 cm (median, 14 cm). All 29 tumors had a
      myxoid component, with a range from 12 to 100% (median, 73%). The range of
      transitional component for all 29 tumors was 0 to 88% (median, 11%). Twenty-one
      tumors had transitional areas (range, 4-88%). The range of round cell component
      for all 29 tumors was 0 to 58% (median, 0%). Twelve tumors had round cell areas
      (range, 1-58%). Seventeen patients are either alive without disease, or died from
      unrelated causes at 24-202 months (median, 96 months). Twelve patients are either
      alive with metastases or died of disease at 10 to 180 months (median, 53 months).
      Patients with > 5% round cell component in their initial tumor had a
      statistically significant higher rate of metastasis or death due to disease than
      those with < or = 5% round cell liposarcoma (p = 0.05). In addition, patients
      with myxoid liposarcoma with transitional areas did not fare worse than those
      with myxoid liposarcoma alone. In conclusion, we found that a round cell
      component of > 5% portends a higher risk of metastasis or death from disease.
      Furthermore, transitional areas alone do not appear to alter the prognosis of
      myxoid liposarcoma. Thus, only those areas that are unequivocally round cell
      liposarcoma should be designated as high grade.

PMID- 8554107
TI  - Melanosis peritonei associated with enteric duplication cyst. A case report.
AB  - Melanosis peritonei is extremely rare, and only five cases have been reported in
      the English literature, four in association with ovarian dermoid cysts, and one
      with a peritoneal cyst. We describe an additional case occurring in a girl two
      years of age who also had an enteric cyst. This is the first reported case of
      melanosis peritonei not associated with an ovarian teratoma, but with an enteric
      duplication cyst. Melanophages were present focally in the submucosa, superficial
      muscle layer, and ulcer bases of the cyst and extensively as small nodules on the
      peritoneal surface and in the omentum. The tendency of perivascular nodular
      aggregation of melanophages favors a hematogenous (or lymphatic) spread rather
      than implantation. Although clear evidence of melanocytic aggregation is lacking,
      are speculate that the melanin originated from the esophageal-like squamous
      mucosa of the cyst.

PMID- 8554108
TI  - Glassy cell carcinoma of the colon with human chorionic gonadotropin-production.
      A case report with immunohistochemical and ultrastructural analysis.
AB  - An unusual tumor in the descending colon with human chorionic gonadotropin-beta
      (HCG-beta) production and histological features of a "glassy cell" carcinoma is
      presented. Glassy cell carcinoma has been described in the uterus and fallopian
      tubes as well as the cervix, but in these locations the tumor is not HCG-beta
      producing. Glassy cell carcinomas have been described in some cases as having
      glandular and squamous differentiation as well as marked cellular pleomorphism.
      The tumors are generally associated with a poor prognosis.

PMID- 8554109
TI  - T-cell-rich B large-cell lymphoma simulating lymphocyte-rich Hodgkin's disease.
AB  - Immunophenotypic analysis of 50 cases fulfilling the histologic criteria for
      mixed cellularity Hodgkin's disease disclosed nine cases with a B-cell, non
      Hodgkin's phenotype (CD20+, CD15-, CD30-, EMA-). The cases were characterized by
      a diffuse small lymphocytic milieu, interspersed atypical large cells including
      classic Reed-Sternberg cells, and infrequent plasma cells, eosinophils, and L&H
      cells. The male:female ratio was 7:2 (aged 22-65 years, median 39 years). Three
      patients were Ann Arbor stage II, two stage III, and four stage IV. The patients
      presented with generalized lymphadenopathy (four), mesenteric lymph node
      involvement (two), splenomegaly (four), and bone marrow involvement (three). Four
      patients were treated with standard Hodgkin's disease protocols. Two attained a
      complete response and two a partial response; all relapsed and died. Four of five
      patients treated for large-cell lymphoma achieved a complete response and are
      currently alive without evidence of disease. The one patient with an initial
      partial response relapsed and died. We conclude that immunophenotypic analysis is
      essential in cases of histologic mixed cellularity Hodgkin's disease, especially
      in those with lymphocyte-rich morphology. Cases with a B-cell phenotype should be
      diagnosed and treated as T-cell-rich B large-cell lymphoma.

PMID- 8554110
TI  - Utility of a paraffin section-reactive CD56 antibody (123C3) for characterization
      and diagnosis of lymphomas.
AB  - Although expression of CD56 (neural cell adhesion molecule, a natural killer cell
      marker) is uncommon among lymphomas, this feature has defined a distinctive and
      important category of lymphoma: the putative natural killer (NK) cell lymphoma,
      which shows a predilection for the upper aerodigestive tract, skin, skeletal
      muscle, and other extranodal sites and pursues an aggressive clinical course.
      Thus far, CD56 expression can be reliably analyzed only on fresh or frozen
      tissues. In this study, we evaluated the sensitivity and specificity of a CD56
      antibody, 123C3, when applied on routine formalin-fixed, paraffin-embedded
      tissues for analysis of lymphomas, by comparing the staining results with those
      obtained on frozen tissues using the CD56 antibody NKH1. The 123C3 antibody
      worked on paraffin sections only with prior antigen retrieval using a pressure
      cooker or a microwave oven. Among 32 CD56+ T/NK cell lymphomas and one CD56+ B
      lymphoblastic lymphoma, the neoplastic cells showed crisp membrane staining with
      123C3 in all cases. None of the 24 CD56- T-cell lymphomas and 50 CD56-B-cell
      lymphomas stained with 123C3. In normal or reactive lymphoid tissues from a
      variety of sites, there were few small lymphocytes (< 0.1%) that showed cell
      membrane staining with 123C3, although occasional plasma cells might show
      cytoplasmic staining. We conclude that with suitable antigen retrieval
      procedures, 123C3 can be reliably applied on routine paraffin sections for
      detection of CD56 expression in lymphomas. Furthermore, this antibody can be used
      to support a diagnosis of lymphoma or to detect residual disease for cases of
      CD56+ T/NK cell lymphoma in which the neoplastic lymphoid cells are small and
      show minimal atypia, especially in small biopsies.

PMID- 8554111
TI  - "Small" B-cell non-Hodgkin's lymphomas with splenomegaly at presentation are
      either mantle cell lymphoma or marginal zone cell lymphoma. A study based on
      histology, cytology, immunohistochemistry, and cytogenetic analysis.
AB  - Only 1 to 2% of all non-Hodgkin's lymphomas (NHL) present with an enlarged
      spleen, most of them "small B-cell lymphomas." Recently, several reports have
      identified these lymphomas as marginal zone B-cell lymphomas. We reviewed 39
      cases of NHL presenting with an enlarged spleen without lymphadenopathy,
      documented by fixed and frozen material. Two were peripheral T-cell lymphomas,
      four diffuse large B-cell lymphomas, and 14 hairy cell leukemias. The remaining
      19 belonged to the "small B-cell" category and constitute the focus of our study.
      Subtyping was achieved by combining morphology, immunophenotype, and cytogenetic
      features according to the proposal of the International Lymphoma Study Group; in
      addition, analysis of the peripheral blood and bone marrow smears was performed
      adopting the French-American-British (FAB) criteria. From this study, we can
      conclude that most "small B-cell" NHL of the spleen were either mantle cell
      lymphomas or marginal zone cell lymphomas and, by peripheral blood analysis, that
      the mantle cell lymphomas corresponded to intermediate lymphocytic lymphoma and
      the marginal zone cell lymphomas to splenic lymphomas with villous lymphocytes.
      As a result, several diagnostic criteria can be proposed that may be helpful in
      differentiating mantle cell lymphoma from marginal zone cell lymphoma in the
      spleen.

PMID- 8554112
TI  - Pleomorphic large cell lymphomas of the mediastinum.
AB  - Nine cases of primary non-lymphoblastic, non-Hodgkin's large cell lymphomas of
      the mediastinum characterized by a highly pleomorphic histologic appearance are
      described. The patients, four women and five men, were aged 30 to 65 years. All
      patients presented with symptoms referable to their tumors, including cough,
      chest pain, dyspnea, pleural effusion, and superior vena cava syndrome. Clinical
      and pathologic staging in all patients showed that the bulk of the tumor was
      confined to the chest cavity at the time of initial diagnosis, with local
      infiltration into the neck, lung hilum, and surrounding mediastinal structures.
      Three different histological growth patterns were observed: one composed of a
      diffuse proliferation of pleomorphic, highly atypical cells with bizarre nuclear
      features that closely resembled a high grade sarcoma; another one composed of
      sheets of large, epithelial-appearing atypical cells suggestive of anaplastic
      carcinoma; and another pattern characterized by a pleomorphic proliferation of
      large lymphoid cells admixed with numerous scattered Reed-Sternberg-like cells
      reminiscent of the lymphocyte-depleted variant of Hodgkin's disease.
      Immunohistochemical studies on paraffin-embedded tissue sections in all cases
      showed positive staining of the tumor cells with CD20 and CD45 antibodies and
      negative staining with a large panel of markers, including broad-spectrum
      keratin, CAM 5.2, carcinoembryonic antigen, epithelial membrane antigen,
      vimentin, actin, desmin, HMB 45, S-100 protein, CD3, CD15, CD30, and CD45RO.
      Because of their location restricted to the anterior mediastinum, frequent lack
      of recognizable lymph node architecture, and bizarre cytologic features, the
      present group of lesions posed difficulties for diagnosis, their correct
      identification was achieved through the application of a panel of
      immunohistochemical markers. An awareness of these unusual histologic appearances
      of primary large cell lymphoma in the mediastinum and inclusion of a broad panel
      of lymphoid markers are therefore recommended for the evaluation of pleomorphic,
      undifferentiated malignant neoplasms of this anatomic region.

PMID- 8554113
TI  - Malignant glomus tumor. A case report of widespread metastases in a patient with
      multiple glomus body hamartomas.
AB  - Glomus tumors are characteristically benign solitary tumors. A few cases of
      malignant glomus tumors have been reported; however, they are usually only
      locally invasive, and metastases are exceedingly rare. We report a case of
      widespread metastases of a malignant glomus tumor involving the skin, lungs,
      jejunum, liver, spleen, and lymph nodes in a 63-year-old man with end-stage
      chronic renal failure. At autopsy, multiple glomus body hamartomas were also
      noted throughout the dermis proximal to the skin tumors. Histologically, the
      tumor was composed of monotonous round cells in solid sheets and investing
      numerous capillary-sized vessels. Approximately four to six mitoses were present
      per high-power field. The tumor cells were strongly immunoreactive for actin and
      vimentin, and ultrastructurally there were whorls of microfilaments with focal
      condensations. This case is exceptional because of its aggressive course.

PMID- 8554114
TI  - Primary embryonal rhabdomyosarcoma of long bone. Case report and review of the
      literature.
AB  - We report a case of primary embryonal rhabdomyosarcoma of long bone, presenting
      as a lytic destructive bone tumor in the right femoral diaphysis of a 7-year-old
      girl. To our knowledge, this is only the third report of this entity. The
      neoplasm was a pure embryonal rhabdomyosarcoma with numerous rhabdomyoblasts.
      Immunohistochemistry confirmed the diagnosis: The cells were reactive with
      antibodies directed against desmin, muscle-specific actin, and myoglobin. No
      other neoplastic mesenchymal component was present within the tumor. Although
      rare, primary rhabdomyosarcoma, along with Ewing's tumor and osteosarcoma, should
      be considered in the differential diagnosis of malignant bone tumors in
      childhood.

PMID- 8554115
TI  - Concurrent medullary and papillary carcinomas of thyroid with lymph node
      metastases. A collision phenomenon.
AB  - The simultaneous occurrence of two distinct neoplasms derived from different
      cells of origin is a recognized, albeit rare, entity. In the thyroid, such
      lesions could consist of medullary carcinoma composed of parafollicular C cells
      and well-differentiated carcinoma showing follicular epithelial cell
      differentiation. We report a patient whose thyroid contained calcitonin
      immunoreactive medullary carcinoma and thyroglobulin-positive papillary
      carcinoma, clearly separated from each other. The tumors metastasized to regional
      lymph nodes, where they formed foci of composite medullary and papillary
      carcinoma, with each component maintaining a distinct immunophenotypic profile.
      The composite metastases are best regarded as collision tumors, as each primary
      neoplasm exhibited only one line of differentiation. Given the high incidence of
      papillary carcinoma, the occurrence of the two tumors may be a coincidence.
      Alternatively, a common tumorigenic stimulus triggering neoplastic transformation
      of both parafollicular C cells and follicular epithelial cells is a plausible
      explanation for such a phenomenon.

PMID- 8554116
TI  - Struma ovarii with metaplasia.

PMID- 8554117
TI  - Nuchal nitty-gritty.

PMID- 8554118
TI  - CD56 lymphomas.

PMID- 8554119
TI  - Anti-metallothionein labeling.

PMID- 8554120
TI  - Primary bilateral renal lymphoma.

PMID- 8554121
TI  - Contributions of molecular genetics to the clinical management of colorectal
      cancer.
AB  - Molecular genetics is a tool that can be learned as a language to assist
      clinicians in the management of colorectal cancer patients. Following a brief
      review of the genetic controls of colorectal cancer, the author focuses on the
      models of the Registry for Familial Adenomatous Polyposis and the Registry for
      Hereditary Nonpolyposis Colon Cancer to demonstrate most vividly the impact
      molecular genetics is currently having on the practical management of colon
      cancer. Recent discoveries of K-ras oncogene mutations in stool cultures and the
      prognostic implications of mutations of the TP53 and DCC genes are discussed in
      the context of future applications to the management of patients.

PMID- 8554122
TI  - Intra-abdominal sepsis impairs colonic reparative collagen synthesis.
AB  - BACKGROUND: Intra-abdominal infection is generally considered a contraindication
      to primary colon anastomosis. In order to elucidate the mechanisms by which
      sepsis affects colonic healing, we studied anastomotic new collagen and protein
      synthesis and collagen gene expression in a relevant animal model. METHODS: Forty
      male Sprague-Dawley rats (240 to 260 g) underwent sham laparotomy (SHAM, n = 18)
      or cecal ligation and single puncture (CLP, n = 22). After 24 hours, animals
      underwent single-layer left colon anastomosis. Animals were sacrificed either 1
      or 4 days postanastomosis. Anastomotic segments of colon were excised, minced,
      and incubated with 4.5 muCi 3H-proline. After 3 hours, tissue 3H-proline
      incorporation was quantitated as an index of total new protein synthesis. The
      protein fraction was then digested with purified collagenase enzyme to determine
      3H-proline incorporation into collagenase-digestible protein, an index of new
      collagen synthesis. Total RNA was extracted from anastomotic tissue samples and
      subjected to Northern blot analysis for type I and type III collagen genes.
      RESULTS: Intra-abdominal sepsis resulted in markedly less new collagen synthesis
      1 day postanastomosis (9,163 +/- 1,234 versus 3,744 +/- 444 disintegrates per
      minute 3H-proline/mg of protein, P < 0.0001) and 4 days postanastomosis (8,462 +/
      956 versus 5,708 +/- 802 dpm/mg of protein P < 0.05). Noncollagenous protein
      synthesis was also impaired in anastomotic tissue from CLP rats on
      postanastomosis day 1 (37,497 +/- 3,740 versus 18,593 +/- 2,695 dpm/mg of of
      protein, P < 0.001) and postanastomosis day 4 (28,238 +/- 834 versus 17,784 +/-
      1,415 dpm/mg of of protein, P < 0.0001). The expression of type I and type III
      collagen was altered relative to the normal temporal sequence observed in SHAM
      animals. CONCLUSION: Intra-abdominal infection impairs colonic reparative
      collagen and protein synthesis. In addition, regulation of type I and type III
      collagen genes is altered by intra-abdominal sepsis, and the alteration likely
      contributes to impaired new collagen synthesis and decreased colonic mechanical
      strength.

PMID- 8554123
TI  - Matrix alters the proliferative response of enterocytes to growth factors.
AB  - BACKGROUND: Enterocyte growth and differentiation along the crypt-villus axis is
      a highly controlled process. Crypt cells divide to produce enterocytes that
      migrate along the villus axis prior to terminal differentiation. Growth factors
      and basement membrane may be involved in the regulation of this process. METHODS:
      IEC-6 proliferation was measured in cells grown on laminin or collagen I by
      measuring the conversion of Owen's reagent to formazan. Cells were grown with no
      growth factor, one growth factor (ie, epidermal growth factor, insulin-like
      growth factor-I, or transforming growth factor-alpha), or a combination of
      factors. RESULTS: Enterocyte proliferation was increased in all groups given
      mitogenic growth factors with additive increases in those given combinations.
      Enterocytes grown on laminin showed a significantly decreased proliferative
      response to mitogenic growth factors in all experimental groups. Matrix did not
      alter seeding efficiency or cell viability. CONCLUSION: Basement membrane may
      play a role in the regulation of cell proliferation along the crypt-villus axis.

PMID- 8554124
TI  - Donor lazaroid pretreatment improves viability of livers harvested from non-heart
      beating rats.
AB  - BACKGROUND: Lazaroids are potent inhibitors of lipid peroxidation. Whether the
      compounds can benefit the liver procured from non-heart-beating donors (NHBDs) is
      unknown. METHODS: Donor rats were pretreated with lazaroid U74006F (4.5 mg/kg) 1
      hour before cardiac arrest, and transplantation was performed in the rats with
      donor cardiac arrest from 0 to 60, 100, 120, 140, and 160 minutes as lazaroid
      pretreated groups. The same number of liver transplantations were done in each
      paired control group without donor lazaroid pretreatment. Recipient survival
      rates, bile secretion, serum enzymes, and a lidocaine metabolism test were
      analyzed. RESULTS: Donor lazaroid pretreatment significantly increased recipient
      3-day survival rates in groups with 60, 100, and 120 minutes of warm ischemia and
      7-day survival with 60 minutes of warm ischemia. Also, the pretreatment increased
      bile secretion and reduced serum aspartate aminotransferase and lactate
      dehydrogenase levels in the lazaroid-pretreated groups. CONCLUSIONS: Donor
      U74006F pretreatment improves viability of livers procured from NHBDs.

PMID- 8554125
TI  - Preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative
      radiation therapy for adenocarcinoma of the pancreatic head.
AB  - BACKGROUND: Local recurrence in the bed of the resected pancreas is the most
      common site of tumor recurrence following a standard pancreaticoduodenectomy (PD)
      for adenocarcinoma of the pancreatic head. In an attempt to improve local and
      regional disease control and thereby enhance the quality and length of survival
      in patients undergoing potentially curative PD, we have used a protocol of
      preoperative multimodality therapy. PATIENTS AND METHODS: All patients were
      treated with external-beam radiation (30.0 or 50.4 Gy) and concomitant 5
      fluorouracil (300 mg/m2 per day) prior to PD. Electron-beam intraoperative
      radiation therapy was given to the bed of the resected pancreas before
      reconstruction. Patients were assessed for recurrence by physical examination,
      chest roentgenography, and computed tomography scan performed at 3-month
      intervals following treatment. RESULTS: Thirty-nine patients completed all
      therapy; 1 perioperative death occurred. Thirty-eight tumor recurrences have been
      documented in 29 patients at a median of 11 months from the date of diagnosis; 23
      patients died of disease. The liver was the most frequent site of recurrence, and
      liver metastases were a component of treatment failure in 53% of patients.
      Isolated local or peritoneal recurrences were documented in only 4 patients
      (11%). The only significant clinical or pathologic variable predictive of local
      regional recurrence was a previous laparotomy and intraoperative biopsy. The
      median survival of all 39 patients was 19 months, and the 4-year actuarial
      survival rate was 19%. CONCLUSIONS: Preoperative chemoradiation, PD, and electron
      beam intraoperative radiation therapy for adenocarcinoma of the pancreatic head
      have resulted in improved local-regional tumor control, with distant metastatic
      disease becoming the predominant site of tumor recurrence. Future treatment
      strategies should incorporate effective multimodality therapy for local-regional
      disease as demonstrated in this study. Major improvements in overall survival
      will likely await the development of systemic or regional therapy for liver
      metastases.

PMID- 8554126
TI  - Proliferation tissue polypeptide antigen distinguishes malignant mucinous
      cystadenocarcinomas from benign cystic tumors and pseudocysts.
AB  - BACKGROUND: Cystic lesions of the pancreas include inflammatory pseudocysts,
      serous cystadenomas, and mucinous cystic tumors, some of which are malignant.
      Previous studies have shown that malignant mucinous tumors differ from benign
      pancreatic cysts in proliferative activity, secretion of tumor markers, and
      expression of growth factor receptors. Analysis of aspirated cyst fluid for tumor
      markers, viscosity, and cytologic examination has been proposed as an aid to
      preoperative differential diagnosis. Tissue polypeptide antigen (TPA) is a
      soluble proliferation antigen produced by rapidly dividing tissues, including
      conventional ductal pancreatic carcinoma. TPA levels in pancreatic cyst fluids
      have not been reported. METHODS: Tissue polypeptide antigen levels were
      determined in 46 pancreatic cyst fluids using a commercial immunoassay technique.
      RESULTS: Mucinous cystadenocarcinomas exhibited significantly higher levels of
      cyst fluid TPA than benign cystic lesions, including pseudocysts, serous
      cystadenomas, and benign mucinous cystadenomas (mean 910,672 U/mL, median 300,900
      U/mL, range 16,600 to 4,210,000 U/mL for malignant mucinous cystadenocarcinomas;
      versus mean 16,082 U/mL, median 2,455 U/mL, range 0 to 155,000 U/mL for benign
      cystic lesions considered as a group; P < 0.0002). In 75% of the malignant cysts,
      the TPA values were in excess of 100,000 U/mL. Pseudocysts exhibited the lowest
      TPA levels (mean 2,108 U/mL, median 604 U/mL, range 0 to 20,240 U/mL) and were
      significantly lower than the values observed in cystic tumors (P < 0.0005).
      Serous and benign mucinous tumors had intermediate levels of TPA. CONCLUSIONS:
      Elevated levels of the proliferation antigen TPA in malignant pancreatic cysts
      correlate with earlier observations of increased proliferative activity and
      overexpression of growth factor receptors in these tumors. The TPA measurement
      may be a useful addition to previously reported cyst fluid markers to aid in
      preoperative differential diagnosis. Markedly elevated or very low values
      indicate a malignant or benign cyst, respectively.

PMID- 8554127
TI  - Pancreaticoduodenectomy for benign disease.
AB  - BACKGROUND: Surgeons are often called upon to perform pancreaticoduodenectomy for
      either suspicion of malignancy or symptoms due to benign disease. Perioperative
      morbidity and mortality following pancreaticoduodenectomy have decreased markedly
      over the last 2 decades. In response, many surgical centers advocate expanding
      the indications for pancreaticoduodenectomy to include lesions other than
      periampullary carcinoma. PATIENTS AND METHODS: A retrospective review of medical
      records for 108 patients undergoing pancreaticoduodenectomy for benign disease at
      The Johns Hopkins Medical Institutions over 100 months was completed. The subset
      of patients with a histopathologic diagnosis of chronic pancreatitis was
      identified and compared with patients undergoing pancreaticoduodenectomy for
      other benign conditions. RESULTS: The mortality rate for the present series was
      less than 1%. Perioperative complications, the majority of which were self
      limited, occurred in 51% of patients. The most common complication was delayed
      gastric emptying. Pancreatic anastamotic leak occurred in 18% of patients and
      developed significantly more frequently in patients with benign diseases other
      than chronic pancreatitis (31% versus 8%, P < 0.05). CONCLUSION: Among
      appropriately selected patients, the rates of perioperative mortality and serious
      morbidity are low, and concerns about mortality and morbidity should not prevent
      an aggressive approach to surgical resection in patients with benign disease.

PMID- 8554128
TI  - Familial segregation in the occurrence and severity of periampullary neoplasms in
      familial adenomatous polyposis.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) patients often develop
      periampullary adenomas that may progress to periampullary cancer, a common cause
      of death in this population. The risk of periampullary cancer in FAP is unclear,
      and variables that predict the occurrence and severity of periampullary tumors
      are not well understood. The specific aim of this study was to determine whether
      the risk of periampullary neoplasia segregates in specific FAP families.
      MATERIALS AND METHODS: A total of 144 FAP patients from 74 families were either
      screened by gastroduodenoscopy (n = 132) or information was obtained from
      surgical or autopsy reports (n = 12). The severity of periampullary neoplasia was
      recorded for each patient and graded based on maximum polyp size and histology.
      Linear regression was used to determine the significance of a number of variables
      with respect to periampullary neoplasia. A blood sample was available from at
      least one member of 50 unrelated families and used to detect germline mutations
      in codons 686 through 1693 of the adenomatous polyposis coli (APC) gene. RESULTS:
      Statistically significant familial segregation was found for the incidence and
      severity of periampullary neoplasia (P < 0.02). Age was also a statistically
      significant variable (P < 0.01). No correlation was observed between specific APC
      germline mutations and periampullary polyp frequency and severity. CONCLUSIONS:
      The occurrence and severity of periampullary neoplasms in patients with FAP
      segregates in families. This familial association may be related to as yet
      unidentified modifier genes or perhaps common environmental factors. These
      results should prove useful in developing upper gastrointestinal screening
      protocols for FAP patients at risk for periampullary neoplasia.

PMID- 8554129
TI  - Pitfalls of distal pancreatectomy for relief of pain in chronic pancreatitis.
AB  - PURPOSE: To examine whether preoperative computed tomography (CT) scans and
      pancreatograms can: (1) identify patients with chronic pancreatitis localized to
      the tail of the pancreas; and (2) select those patients who can obtain pain
      relief from a distal pancreatectomy. PATIENTS AND METHODS: Twenty patients were
      identified on whom the authors had performed distal pancreatectomy for relief of
      pain between January 1, 1991 and August 1, 1994. The results of surgery were
      classified as good, fair, or poor based on return to work and need for narcotics
      or rehospitalization. RESULTS: Eleven patients had good, 3 fair, and 6 poor
      results. All 7 patients with pseudocysts of the tail of the pancreas had good
      results, while 9 of 13 patients without pseudocysts had poor results. No other
      finding on CT scan, pancreatography, or laparotomy predicted successful pain
      relief by distal pancreatectomy. Furthermore, 3 patients had unexpected carcinoma
      found at the time of surgery. CONCLUSIONS: Even when anatomic evidence suggests
      that chronic pancreatitis primarily involves the tail of the pancreas and there
      is a stricture of the midpancreatic duct that is believed to cause the symptoms,
      distal pancreatectomy seldom provides sustained pain relief. Unsuspected
      carcinoma of the body and tail of the pancreas occurs frequently in this subset
      of patients with chronic pancreatitis.

PMID- 8554130
TI  - Biliary carcinoembryonic antigen levels are a marker for cholangiocarcinoma.
AB  - BACKGROUND: Cholangiocarcinoma develops in 5% to 15% of patients with choledochal
      cysts, sclerosing cholangitis, and intrahepatic stones. The detection of
      cholangiocarcinoma in patients with premalignant biliary conditions has been
      difficult. Serum levels of carcinoembryonic antigen (CEA) have been neither
      sensitive nor specific for the diagnosis of cholangiocarcinoma. However, CEA has
      been shown to be present in cholangiocarcinomas by immunohistochemical staining.
      Therefore, we measured the level of CEA excreted in bile in patients with benign
      strictures, premalignant biliary diseases, and cholangiocarcinoma. PATIENTS AND
      METHODS: Bile was obtained from transhepatic stents in patients with benign
      biliary strictures (34), choledochal cysts (5), primary sclerosing cholangitis
      (6), intrahepatic cholelithiasis (5), and perihilar cholangiocarcinoma (25).
      Samples were analyzed for CEA using a solid phase, two-site immunoenzymetric
      assay. RESULTS: Biliary CEA levels were significantly elevated (P < 0.01) in
      patients with cholangiocarcinoma (50.2 +/- 5.8 ng/mL) and intrahepatic
      cholelithiasis (57.4 +/- 10.4 ng/mL) compared with patients with benign
      strictures (10.1 +/- 3.9 ng/mL). Patients with sclerosing cholangitis (21.6 +/-
      3.9 ng/mL) and choledochal cysts (20.0 +/- 16.5 ng/mL) had intermediate levels.
      In 5 patients undergoing resection of perihilar cholangiocarcinomas, the mean
      biliary CEA level decreased from a preoperative level of 46.8 +/- 6.7 ng/mL to a
      postoperative level of 11.3 +/- 5.6 ng/mL (P < 0.02). In 4 patients with
      progression of cholangiocarcinoma, biliary CEA increased from a mean of 53.3 +/-
      6.9 ng/mL to 98.3 +/- 12.2 ng/mL (P < 0.02) over a mean interval of 9.5 months.
      CONCLUSIONS: Increased levels of CEA can be detected in the bile of patients with
      chlolangiocarcinoma. Monitoring these levels may have a role in the management of
      cholangiocarcinoma as well as premalignant biliary conditions such as choledochal
      cysts and sclerosing cholangitis.

PMID- 8554131
TI  - The effect of small-diameter H-graft portacaval shunts on portal blood flow.
AB  - BACKGROUND: Small-diameter prosthetic H-graft portacaval shunts have been shown
      to promote preservation of total hepatic blood flow relative to large-diameter H
      graft shunts. Nonetheless, specific changes in portal hemodynamics occurring with
      small-diameter H-graft shunting are unknown. This study was undertaken to
      evaluate changes in portal flow that occur with these shunts. METHODS: Portal
      vein and inferior vena cava (IVC) blood flow were determined intraoperatively in
      36 consecutive adults before and after prosthetic H-graft portacaval shunting
      using color-flow Doppler ultrasound. Postshunt measurements were made immediately
      cephalad and caudad to the shunt. Comparisons were undertaken using a paired
      Student's t-test with 95% confidence. RESULTS: Portal pressures decreased in all
      (P < 0.001), but never to normal. Postshunt portal flow cephalad and caudad to
      the shunt were not different from preshunt flow (P = 0.09, P = 0.28,
      respectively), although they were different from each other (P = 0.004).
      Postshunt IVC flow cephalad to the shunt was greater than caudad IVC flow (P =
      0.004) and greater than preshunt IVC flow (P < 0.001), reflecting high flow
      through the shunt into the IVC. CONCLUSIONS: Small-diameter prosthetic H-graft
      portacaval shunts divert a significant amount of blood from the portal vein and
      significantly decrease portal pressures. The decreases in portal pressures with
      shunting are significant whereas changes in portal blood flow into the liver are
      not. These findings help explain the low incidence of variceal rebleeding and
      hepatic dysfunction after these shunts.

PMID- 8554132
TI  - Drainage is unnecessary after elective liver resection.
AB  - PURPOSE: A prospective, randomized trial was performed to determine if intra
      abdominal drainage catheters are necessary after elective liver resection.
      PATIENTS AND METHODS: Between April 1992 and April 1994, 120 patients subjected
      to liver resection, stratified by extent of resection and by surgeon, were
      randomized to receive or not receive operative closed-suction drainage. Operative
      blood loss was not an exclusion criteria, and no patient who consented to the
      study was excluded. RESULTS: Eighty-seven patients (73%) had resection of one
      hepatic lobe or more (27 lobectomies, 54 trisegmentectomies, and 6 bilobar
      atypical resections) and 33 had less than a lobectomy (8 wedge resections or
      enucleations, 9 segmentectomies, and 16 bisegmentectomies). Eighty-four patients
      (70%) had metastatic cancer and 36 patients (30%) had primary liver pathology.
      There were no differences in outcome, including length of hospital stay (no
      drain, 13.4 +/- 0.9 days; drain, 13.1 +/- 0.8 days; P = not significant [NS]),
      mortality (no drain, 3.3%; drain, 3.3%), complication rate (no drain, 43%; drain,
      48%; P = NS), or requirement for subsequent percutaneous drainage (no drain, 18%;
      drain, 8%; P = NS). All infected collections (n = 3) occurred in operatively
      drained patients. Two other complications were directly related to the
      operatively placed drains. One patient developed a subcutaneous abscess at the
      drain site, and a second developed a subcutaneous drain tract tumor recurrence as
      the only current site of recurrence. CONCLUSION: In the first 50 consecutive
      resections performed since the conclusion of this trial, only 4 patients (8%)
      have required subsequent percutaneous drainage. We conclude that abdominal
      drainage is unnecessary after elective liver resection.

PMID- 8554133
TI  - Glucose-induced islet hyperemia is mediated by nitric oxide.
AB  - PURPOSE: To determine whether hyperglycemia affects pancreatic islet
      microcirculation in vivo and whether nitric oxide is a mediator. METHODS: Islet
      blood flow was measured before and after infusion of glucose during in vivo
      microscopy of mouse pancreatic islet. The pancreas of male BALB/c mice was
      exteriorized and viewed under the microscope utilizing monochromatic transmitted
      light. The carotid artery and tail vein were cannulated and systemic blood
      pressure was monitored continuously. Under fluorescent light, a 0.02 mL bolus of
      2% fluorescein isothyocyanate (FITC-albumin) was injected intra-arterially and
      the first pulse of FITC-albumin through an islet capillary was videorecorded.
      Following equilibration, either glucose or normal saline 300 mg/g of body weight
      was given intravenously. Five minutes later, a second bolus was given and the
      second pulse was videorecorded. The study was repeated in the presence of N omega
      nitro-L-arginine methyl ester (L-NAME). The FITC-albumin bolus mean transit time
      (TT) and observed cross time (OCT) through the islet were calculated using slow
      motion video analysis of the recorded images. RESULTS: Infusion of glucose
      resulted in a significant increase in islet blood flow with no change in systemic
      blood pressure: baseline TT was 20 +/- 1.3 pixel/0.03 sec and baseline OCT was
      0.6 +/- 0.04 seconds; during hyperglycemia, TT was 16.1 +/- 1 pixel/0.03 sec, and
      OCT was 0.48 +/- 0.03 seconds (n = 11, P < 0.05 versus basal via paired t-test).
      Continuous infusion of L-NAME negated the effect of hyperglycemia on islet blood
      flow: baseline TT was 20 +/- 1.8 pixel/0.03 sec and OCT was and 0.6 +/- 0.05
      seconds; during hyperglycemia, TT was 20 +/- 1.1 pixel/0.03 sec and OCT was 0.6
      +/- 0.33 seconds (n = 10; P < 0.05 versus glucose via unpaired t-test).

PMID- 8554134
TI  - Adaptive regulation of amino acid transport in nutrient-deprived human hepatomas.
AB  - BACKGROUND: Malignant cells require increased amounts of amino acids, in
      particular glutamine and leucine, to support DNA and protein biosynthesis.
      Although plasma concentrations in the center of solid tumors can be much lower
      than normal circulating levels, it is still unknown how tumor cells can survive
      despite low amino acid levels. We examined the effects of glutamine or leucine
      deprivation on cell growth and amino acid transport activity in two human
      hepatoma cell lines, SK-Hep and HepG2. METHODS: We studied the transport of
      glutamine, leucine, alanine, and arginine. The carrier-mediated uptake of 3H
      amino acids was determined in cells cultured in normal and amino acid-deprived
      media. RESULTS: The growth of both cell lines was dependent on the concentration
      of glutamine and leucine. In SK-Hep, there was a significant increase in initial
      rate glutamine transport activity in the glutamine-deprived group, attributable
      to an increase in transporter affinity (Km; 0.6 mmol/L [control], 385 +/- 43
      mumol/L; 0.1 mmol/L, 221 +/- 11 mumol/L; P < 0.01). At low glutamine
      concentration, the saturable Na(+)-independent uptake of leucine and arginine as
      well as the Na(+)-dependent uptake of alanine increased significantly in both SK
      Hep and HepG2. Similarly, in leucine-deprived SK-Hep cells, leucine uptake
      increased twofold, but the change was attributable to an enhanced transporter
      capacity (Vmax; 0.2 mmol/L [control], 38,900 +/- 700; 0.0 mmol/L, 75,900 +/-
      4,900 pmol/mg protein per minute; P < 0.001). CONCLUSIONS: Adaptive increases in
      initial rate amino acid transport activities were elicited by glutamine and
      leucine deprivation in these two human hepatoma cell lines. Decreased
      extracellular amino acid levels encountered by tumors in vivo may elicit similar
      adaptive responses that contribute to the maintenance of cytoplasmic levels of
      amino acids essential for growth.

PMID- 8554135
TI  - Carcinoma of the periampullary region: who benefits from portal vein resection?
AB  - BACKGROUND: The prognosis of patients with carcinoma of the periampullary region
      infiltrating the portal vein is dismal. PATIENTS AND METHODS: We assessed the
      morbidity, mortality, and prognosis of pancreatoduodenectomy in 31 patients in
      whom a tangential excision (n = 9) or a segmental resection (n = 22) of the
      portal vein or superior mesenteric vein was performed in an attempt to achieve
      complete tumor removal. RESULTS: There was no postoperative mortality. Tumor
      infiltration of the resected vein could be documented histopathologically in 19
      of the 31 (61.3%) patients. All patients with pancreatic or bile duct carcinoma
      (n = 29) died within 16 months of the resection (median survival 8 months). In
      contrast, 2 patients with cystadenocarcinoma and acinous cell carcinoma are alive
      with no evidence of recurrence at 23 and 54 months, respectively. CONCLUSION:
      Portal vein resection does not prolong survival in patients undergoing partial
      pancreatoduodenectomy for carcinoma of the pancreas or distal bile duct. Only the
      occasional patient with a rare tumor at this region may benefit from this
      approach.

PMID- 8554136
TI  - Treatment of Budd-Chiari syndrome with portosystemic shunt or liver
      transplantation.
AB  - BACKGROUND: Budd-Chiari syndrome is an uncommon disorder caused by obstruction to
      hepatic venous outflow, causing varying degrees of hepatic injury depending on
      the extent, severity, and acuity of the obstruction. PATIENTS AND METHODS: We
      reviewed the indications for operative intervention and the results of treating
      32 patients with Budd-Chiari syndrome seen at Toronto Hospital between 1968 and
      1995. RESULTS: Twenty-one patients underwent portosystemic shunt (PSS) and 7
      patients underwent liver transplantation (LT) as their initial operative
      management. Three patients who initially had PSS subsequently required LT.
      Patients with cirrhosis found on biopsy and preservation of hepatocellular
      function were treated with PSS and showed no difference in outcome when compared
      with patients without cirrhosis (P = 0.35). Patients who were treated by PSS with
      retrohepatic vena caval compression, as shown by high caval gradients had
      outcomes similar to those for patients with low gradients (P = 0.31). Using the
      Kaplan-Meier method, 5-year survival of PSS patients was 57%. Liver
      transplantation was used to manage patients with hepatic decompensation, as well
      as patients with vena caval occlusion or failed PSS. The 5-year Kaplan-Meier
      survival for LT was 67%. CONCLUSIONS: Both PSS and LT are effective options in
      the management of Budd-Chiari syndrome. Portosystemic shunt is the preferred
      initial approach even with cirrhosis or retrohepatic caval compression as long as
      there is preservation of liver function and a patent vena cava. Liver
      transplantation should be used as primary therapy for patients with irreversible
      hepatic decompensation or vena caval occlusion, and it can be an effective
      salvage procedure following failed PSS.

PMID- 8554137
TI  - Hiatal hernia size affects lower esophageal sphincter function, esophageal acid
      exposure, and the degree of mucosal injury.
AB  - BACKGROUND: Since the role of a hiatal hernia in the pathophysiology of
      gastroesophageal reflux disease (GERD) has not been fully elucidated, we studied
      the effects of hiatal hernias on the function of the lower esophageal sphincter
      (LES) and esophageal acid clearance. PATIENTS AND METHODS: Ninety-five
      consecutive patients with GERD diagnosed by 24-hour pH monitoring underwent upper
      gastrointestinal series (UGI), endoscopy, and esophageal manometry. Based on the
      presence (H+) or absence (H-) of a hiatal hernia on UGI series, they were divided
      into two groups: H+ (n = 51) and H- (n = 44). Then, using the size of the hiatal
      hernia, the H+ group was divided into three subgroups: I, H < 3 cm (n = 31); II,
      H 3.0 to 5 cm (n = 14); and III, H > 5 cm (n = 6). RESULTS: Esophageal manometry
      showed that patients with larger hiatal hernias (groups II and III) had a weaker
      and shorter LES and less effective peristalsis compared to patients with a small
      or no hiatal hernia. Prolonged pH monitoring showed that patients with larger
      hiatal hernias were exposed to more refluxed acid and had more severely abnormal
      acid clearance. Endoscopy showed more severe esophagitis among patients with GERD
      and hiatal hernia compared with GERD patients without hiatal hernia, and the
      degree of esophagitis was proportionate to the size of the hernia. CONCLUSIONS:
      Among patients with proven GERD, those with a small hiatal hernia and those with
      no hiatal hernia had similar abnormalities of LES function and acid clearance. In
      patients with larger hiatal hernias, however, the LES was shorter and weaker, the
      amount of reflux was greater, and acid clearance was less efficient.
      Consequently, the degree of esophagitis was worse in the presence of a large
      hiatal hernia.

PMID- 8554138
TI  - Low insertion of hepatic segmental duct VII-VIII is an important cause of major
      biliary injury or misdiagnosis.
AB  - BACKGROUND: The importance of variant anatomy is only mentioned generally in most
      articles in this era of laparoscopic cholecystectomy. We report a series of 14
      patients in whom a seemingly low insertion of hepatic segmental duct VII-VIII was
      clinically important. METHODS: The patients were managed at Duke University
      Medical Center. Two intraoperative videotapes of injury were reviewed. RESULTS:
      Three categories of patients were identified: 6 patients who had injury in
      association with another major injury to the biliary system, 7 patients who had
      an isolated VII-VIII system injury, and 1 patient with a Klatskin tumor in whom
      the unobstructed variant duct was stented. After appropriate evaluation, all
      patients were successfully treated. Several lawsuits resulted, even when the
      injury was seemingly minor. Symptoms developed in all patients who filed
      lawsuits, but none in those who did not. CONCLUSION: Appreciation of the VII-VIII
      biliary variant can lead to avoidance of injury or to a successful repair. The
      injury can easily occur despite "normal" cholangiography. Successful clinical
      outcome does not necessarily correlate with freedom from lawsuits.

PMID- 8554139
TI  - Adjuvant hormonal treatment with peptide YY or its analog decreases human
      pancreatic carcinoma growth.
AB  - BACKGROUND: Recent studies have revealed decreased pancreatic cancer cell growth
      upon administration of peptide YY (PYY). We examined whether adjuvant treatment
      with PYY or its synthetic analog, BIM-43004, would decrease human pancreatic
      adenocarcinoma growth. MATERIALS AND METHODS: Human pancreatic ductal
      adenocarcinomas, MiaPaCa-2 and BxPC-3, were cultured and assessed for growth by
      MTT assay. Pancreatic cancer cells received 500 pmol of PYY or BIM-43004 for 24
      hours prior to 5-fluorouracil (5-FU; 10 micrograms/mL) and leucovorin (40
      micrograms/mL) administration. Cell membrane epidermal growth factor (EGF)
      receptors were analyzed by Western blotting after exposure to peptides and
      chemotherapy. RESULTS: Cancer cell growth was reduced in all groups receiving
      hormonal pretreatment (23% PYY/5-FU/leucovorin versus control; 27% BIM-43004/5
      FU/leucovorin versus control) as compared with groups receiving 5-FU and
      leucovorin only (16% versus control). The EGF receptor expression was reduced by
      30% in cells treated with PYY/5-FU/leucovorin and by 45% in cells treated with
      BIM/5-FU/leucovorin as compared with control cells without treatment. CONCLUSION:
      Human pancreatic cancer cell growth is further decreased when pretreated with PYY
      or its synthetic analog prior to chemotherapy.

PMID- 8554140
TI  - Inflammatory properties of bile from dogs with pigment gallstones.
AB  - BACKGROUND: Gallbladder inflammation and mucus hypersecretion are prominent
      features of cholesterol and pigment gallstones in humans and animals. The factors
      leading to inflammation and mucus hypersecretion are poorly understood. These
      studies examine the inflammatory potential of bile from dogs with pigment
      gallstones. METHODS: Dogs fed a methionine-deficient diet that produces pigment
      gallstones by 6 weeks were compared to normal dogs. Mucus layer thickness,
      myeloperoxidase activity, and interleukin-1-like activities were measured in
      canine gallbladder. The inflammatory potential of canine bile was determined by
      measuring mucus layer thickness, sodium absorption, myeloperoxidase activity and
      interleukin-1-like activity in guinea pig gallbladders exposed to normal and
      lithogenic canine bile for 4 hours. RESULTS: Mean mucus layer thickness,
      myeloperoxidase, and interleukin-1 activity were significantly greater in canine
      gallbladders containing pigment gallstones. Bile from dogs with pigment
      gallstones markedly increased mucus layer thickness, myeloperoxidase activity,
      and interleukin-1 activity and decreased sodium absorption in normal guinea pig
      gallbladder. These effects were not eliminated by centrifuging bile to remove
      crystals and gallstones. CONCLUSIONS: Canine bile from dogs with pigment
      gallstones contains soluble factors capable of causing inflammation in the
      gallbladder wall.

PMID- 8554141
TI  - General surgery in evolution: technology and competence.
AB  - This paper addresses the current status of General Surgery, the direction in
      which it is moving, and how to prepare for future changes. The paper points out
      that, since the predicted effects of new technology on the practice of General
      Surgery are more technical complexity, decreasing invasiveness, and fewer
      traditional operations, the consequences for the training of surgeons, the
      division of responsibilities among specialists, and the organization of surgical
      care will be substantial. In light of the current difficulty in dealing with the
      stresses within General Surgery, the paper discusses how changes in residency
      training and an increased use of Fellowships will enable the specialty to handle
      such disruptive changes in the future.

PMID- 8554142
TI  - Hepatic tumor necrosis factor-alpha production and distant organ dysfunction in a
      murine model of obstructive jaundice.
AB  - BACKGROUND: Multisystem organ dysfunction frequently occurs following obstructive
      jaundice, but its etiology remains unclear. This study was undertaken to evaluate
      the role for endogenous tumor necrosis factor-alpha (TNF-alpha) production in the
      renal and pulmonary injury that accompanies obstructive jaundice. METHODS: Two
      hundred and twenty C57BL/6 mice underwent ligation and division of the common
      bile duct or a sham celiotomy. The animals were randomized to receive either
      placebo or 1 mg/kg BW (low dose) or 15 mg/kg BW (high dose) of a novel TNF-alpha
      inhibitor comprised of two extracellular domains of the p55 TNF receptor linked
      together with polyethylene glycol. Serum bilirubin, creatinine, and urea nitrogen
      were determined. TNF-alpha bioactivity in plasma and organs was determined using
      the WEHI 164 clone 13 cytotoxicity assay. The TNF-alpha messenger RNA was
      detected by reverse transcriptase-polymerase chain reaction. Neutrophil
      infiltration into the lungs and kidney were quantitated by the myeloperoxidase
      assay. RESULTS: Common bile duct ligation and division resulted in rapid and
      sustained increases in serum bilirubin, creatinine, and urea nitrogen, peaking 2
      to 5 days later. Hepatic TNF-alpha production was detected in the liver within 8
      hours following obstructive jaundice, but TNF-alpha production could not be
      detected in the kidney or lung at any time point. Increased neutrophil
      infiltration occurred in the lung following obstructive jaundice peaking 5 days
      after obstructive jaundice. This neutrophil infiltration into the lungs could be
      partially inhibited (62%, P < 0.05) by administration of the novel TNF inhibitor.
      In contrast, neither renal nor hepatic dysfunction were affected by TNF-alpha
      blockade. CONCLUSIONS: Hepatic TNF-alpha production is an integral component of
      the response to obstructive jaundice. A TNF-alpha-mediated inflammatory response
      occurs in the lungs as a result of obstructive jaundice; however, renal and
      hepatic dysfunction do not appear to be TNF-alpha dependent since they cannot be
      affected by TNF-alpha blockade.

PMID- 8554143
TI  - Bile-pancreatic juice replacement not cholinergic- and cholecystokinin-receptor
      blockade reverses acinar cell hyperstimulation after bile-pancreatic duct
      ligation.
AB  - BACKGROUND: Acinar cell inhibitors (eg, atropine) fail to ameliorate clinical and
      experimental acute pancreatitis. We hypothesized that amelioration of pancreatic
      acinar cell hyperstimulation after bile and pancreatic duct ligation is better
      with gut replacement of bile and pancreatic juice than with cholinergic- and
      cholecystokinin (CCK)-receptor blockade. METHODS: Using acinar cell amylase
      activity as an index of hyperstimulation, we studied 63 rats in two sets of
      experiments. Bile-pancreatic juice exclusion from gut--without (set one) and with
      (set two) bile and pancreatic duct obstruction--was treated with atropine and CCK
      receptor antagonist L-364,718, or with enteral replacement of bile-pancreatic
      juice. RESULTS: In the set one experiment, acinar cell hyperstimulation after
      bile-pancreatic juice exclusion was reversed by combined L-364,718 and atropine
      pretreatment. In set two, acinar cell hyperstimulation after bile and pancreatic
      duct ligation was reversed by enteral bile and pancreatic juice replacement, but
      not by combined L-364,718 and atropine pretreatment. CONCLUSIONS: According to
      this experimental corollary of early gallstone impaction, prevention of acinar
      cell hyperstimulation after duct occlusion should be aimed at the source of the
      response to bile-pancreatic juice exclusion, namely, the gut, rather than at the
      target of the response, the pancreatic acinar cell.

PMID- 8554144
TI  - Positron emission tomography to stage suspected metastatic colorectal carcinoma
      to the liver.
AB  - BACKGROUND: Accurate detection of recurrent colorectal carcinoma remains a
      clinical challenge. Positron emission tomography (PET) using 18F
      fluorodeoxyglucose (18FDG) is an imaging technique that allows direct evaluation
      of cellular metabolism. 18F-fluorodeoxyglucose PET was compared to computed
      tomography (CT) and CT portography for staging metastatic colorectal carcinoma.
      PATIENTS AND METHODS: Twenty-four patients previously treated for colorectal
      carcinoma who had suspected recurrence to the liver underwent an 18FDG PET scan
      of the entire body. All patients had either a CT scan of the abdomen (n = 17), a
      CT portogram (n = 18), or both (n = 11). The final diagnosis was obtained by
      tissue pathology in 19 patients and clinical follow-up in 5 patients. RESULTS: A
      total of 60 suspicious lesions were identified. Of the 55 intrahepatic lesions,
      39 were malignant and 16 were benign. Of the 5 extra-hepatic lesions, 4 were
      malignant. The 18FDG PET imaging had a higher accuracy (93%) than CT and CT
      portography (both 76%) in detecting metastatic disease to the liver, and detected
      unsuspected extrahepatic recurrence in 4 patients. Although the sensitivity of
      18FDG PET (90%) was slightly lower than that of CT portography (97%), the
      specificity was much higher (100% versus 9%), including postsurgical sites. 18FDG
      PET altered surgical plans in 6 (25%) of 24 patients. CONCLUSIONS: 18FDG PET is
      extremely useful in staging patients with suspected metastatic colorectal
      carcinoma to the liver.

PMID- 8554145
TI  - Contractile properties of enteric smooth muscle after small bowel transplantation
      in rats.
AB  - BACKGROUND: The effects of small bowel transplantation (SBTx) on the function of
      enteric smooth muscle are not understood. PURPOSE: To study the contractile
      properties of enteric smooth muscle after SBTx in rats. METHODS: Five groups of
      inbred Lewis rats (n > or = 8 each group) were studied: unoperated, naive
      controls; operated controls 1 week (OC1) and 8 weeks after intestinal
      transection/reanastomosis of the proximal jejunum and distal ileum; and 1 week
      (TX1) and 8 weeks (TX8) after syngeneic orthotopic SBTx. Contractile activity of
      circular muscle strips of jejunum was evaluated in tissue chambers. Spontaneous
      contractile activity (force per wet weight tissue) increased in TX1, TX8, and OC1
      rats (P < or = 0.01). Frequency of contractions doubled in OC1 rats (P < or =
      0.001) but was unchanged in the other groups. In the presence of nonadrenergic
      noncholinergic (NANC) blockade, spontaneous contractile activity increased in TX1
      and OC1 (P < or = 0.005) without a change in frequency of contractions.
      Inhibition of neural activity with tetrodotoxoin increased amplitude and
      frequency in all groups. Bethanechol (3 x 10(-6) to 3 x 10(-4) mol/L) increased,
      and norepinephrine (1 x 10(-6) to 1 x 10(-4) mol/L) dose-dependently decreased
      the amplitude and frequency of contractions in all groups; equi-effective
      concentrations, however, did not differ among groups. CONCLUSIONS: The increase
      in contractile activity after intestinal transection/reanastomosis is secondary
      to an increase in frequency of contractions and not amplitude. SBTx increases
      contractile amplitude of circular muscle due, in part, to downregulation of NANC
      nerves but not via muscarinic or adrenergic hypersensitivity. These alterations
      in enteric physiology of intestinal contractile activity may have important
      implications in clinical SBTx.

PMID- 8554146
TI  - Cryoablation of unresectable malignant liver tumors.
AB  - BACKGROUND: Unresectable malignant liver tumors, particularly metastases of
      gastrointestinal origin, are rapidly lethal in a vast majority of patients,
      regardless of treatment. PATIENTS AND METHODS: We evaluated 58 patients by
      laparoscopy and/or laparotomy. Thirty-nine were treated with cryoablation of
      liver tumors using a liquid-nitrogen cryoprobe delivering a tumoricidal
      temperature of -196 degrees C with intraoperative ultrasound monitoring.
      Histologic evaluation showed that 25 patients had colorectal metastases, 3 had
      gastric tumors, 4 hepatocellular carcinomas, 6 carcinoids, and 1 gastrinoma.
      RESULTS: All patients who received complete cryoablation are alive with a mean
      follow-up of 14 months. Five whose treatment could not be completed died between
      3 and 9 months postoperatively. Thirteen patients (28%) have recurrent disease
      and 20 (51%) have no evidence of disease. There were no operative mortalities.
      Postoperative transient elevation of liver function tests and thrombocytopenia
      were noted. All patients received postoperative chemotherapy. CONCLUSION:
      Cryoablation is an active and safe treatment for advanced liver malignancies.

PMID- 8554147
TI  - Intermediate follow-up of laparoscopic antireflux surgery.
AB  - BACKGROUND: Open antireflux surgery is an established long-term treatment for
      chronic gastroesophageal reflux disease. Short-term results of laparoscopic
      antireflux surgery are excellent, but long-term follow-up is not yet available.
      METHODS: Twenty-four-hour ambulatory esophageal pH monitoring and symptom scores
      were collected prior to laparoscopic antireflux surgery and 6 weeks
      postoperatively. These studies were repeated in an unselected cohort of patients
      1 to 3 years after operation. RESULTS: One hundred patients who were > 1 year
      from surgery at the time of the present study volunteered for intermediate follow
      up symptom assessment, and 35 also completed repeat 24-hour monitoring. The
      median interval after surgery among these volunteers was 17 months. Thirty-three
      (94%) had a normal pH study, which correlated with improvements in symptom
      scores. One patient had an abnormal pH study but no reflux symptoms, and 1
      patient with an abnormal study developed recurrent symptoms of reflux after an
      episode of vomiting 11 months postoperatively. CONCLUSIONS: The intermediate-term
      results of laparoscopic fundoplication suggest that long-term efficacy of this
      operation will be equivalent to open fundoplication.

PMID- 8554148
TI  - Failure of antireflux surgery: causes and management strategies.
AB  - BACKGROUND: With wider use of laparoscopic antireflux surgery, failed antireflux
      procedures are likely to become more common. METHODS: The causes of failure,
      management strategies, and outcome were analyzed in a consecutive series of 105
      patients with failed antireflux procedures. RESULTS: Recurrent reflux was the
      most common primary symptom for referral (44.7%), followed by dysphagia (32.3%),
      and a combination of dysphagia and reflux (15.2%). The reasons for failure were
      disruption of the initial antireflux procedure (46%), a displaced repair (23%), a
      too-tight or too-long fundoplication (10%), an unrecognized motor disorder (9%),
      a paraesophageal or axial herniation (6%), or gastric denervation (6%).
      Revisional surgery was required in 71 patients, and 34 patients were managed
      conservatively. Intraoperative assessment during reoperation showed that
      technical errors during the initial procedure were responsible for failure in 40
      of 71 patients. With an individual therapeutic approach, good results were
      achieved in 86% of patients undergoing revisional surgery. CONCLUSIONS: Technical
      factors and inappropriate patient selection are the most common reasons for
      failure of antireflux surgery. An individual therapeutic approach based on an
      exact analysis of the reasons for failure of the initial procedure is essential
      for the successful management of these patients.

PMID- 8554149
TI  - Prognostic value of TP53 and K-ras-2 mutational analysis in stage III carcinoma
      of the colon.
AB  - BACKGROUND: Genetic mutations involving oncogenes and tumor-suppressor genes
      occur in carcinogenesis, and may affect biologic behavior of neoplasms. In this
      study, we analyzed the prognostic value of mutational analysis in colon
      carcinoma. PATIENTS AND METHODS: Archival pathology specimens from 70 consecutive
      patients, resected for stage III colon carcinoma, were analyzed for point
      mutations by amplification and direct sequencing of exons from the K-ras-2 and
      the TP53 genes (topographic genotyping). Mutations were compared with adverse
      histopathologic features (poor differentiation, vascular and lymphatic invasion,
      mucin production) as prognostic markers. RESULTS: Five-year survival was 75% in
      patients with nonmutated lesions, significantly lower (21%) with TP53 mutations
      (P = 0.01), and intermediate with K-ras-2 only (45%) or both K-ras-2 and TP53
      mutations (36%). A TP53 mutation carried the highest relative risk of death
      (2.39; 95% confidence interval, 1.29 to 4.42; P = 0.006). There was an additive
      effect on the risk of death between TP53 mutations and adverse histopathologic
      features. CONCLUSIONS: The information derived from mutational analysis is
      creating new prognostic variables that may play a role in the choice of therapy
      for colorectal carcinoma.

PMID- 8554150
TI  - Laparoscopic surgery in the management of inflammatory bowel disease.
AB  - BACKGROUND: The role of laparoscopic surgery in the treatment of various upper
      and lower gastrointestinal disorders is still under investigation. However, a
      variety of laparoscopic procedures may be applied in the treatment of
      inflammatory bowel disease (IBD). PATIENTS AND METHODS: We present our initial
      results of laparoscopic and laparoscopic-assisted management of IBD in 72
      consecutive patients (37 women and 35 men; mean age 36 years, range 20 to 79).
      The indications for surgery included: terminal ileitis in 29 patients, mucosal
      ulcerative colitis in 23 patients, Crohn's colitis in 11 patients, severe
      perianal Crohn's disease in 4 patients, duodenal Crohn's disease in 3 patients,
      Crohn's rectovaginal fistula in 1 patient, and rectourethral fistula in 1
      patient. The procedures performed included: total abdominal colectomy (TAC) in 30
      patients (22 with total proctocolectomy with ileoanal reservoir, 6 with TAC with
      ileorectal anastomosis, and 2 with TAC with end ileostomy), ileocolic resection
      in 30 patients, diverting loop ileostomy in 6 patients, closure of an end
      ileostomy as an ileorectal anastomosis in 3 patients who already underwent a TAC
      with end ileostomy, and duodenal bypass gastrojejunostomy in 3 patients. RESULTS:
      There were 16 complications in 13 (18%) patients: 3 enterotomies, 4 episodes of
      bleeding, 3 pelvic abscesses, 2 intestinal obstructions, 2 prolonged ileus, 1
      anastomotic leak, and 1 efferent loop obstruction after gastrojejunostomy.
      However, only 3 patients required laparotomy for morbidity, and there was no
      mortality. In 7 (10%) patients, the laparoscopic procedure was converted to a
      laparotomy due to a large inflammatory mass with fistula in 4 patients, bleeding
      in 2 patients, and an enterotomy in 1 patient. The mean operating time was 2.9
      hours (range 0.7 to 6) and the mean length of hospital stay was 6.5 days (range 3
      to 19). When compared with ileocolic resection, total colectomy was associated
      with higher morbidity (30% versus 10%, P < 0.05) and longer hospitalization (8.7
      days [range 4 to 19] versus 5.2 days [range 3 to 7], respectively; P < 0.05).
      CONCLUSIONS: According to this initial experience, laparoscopic surgery is a
      versatile and effective modality in the surgical management of inflammatory bowel
      disease in selected patients. However, laparoscopic total colectomy is associated
      with higher morbidity when compared with ileocolic resection.

PMID- 8554151
TI  - Preliminary experience with laparoscopic intestinal surgery for Crohn's disease.
AB  - BACKGROUND: Laparoscopic techniques are being applied to the surgical management
      of various intestinal conditions, but few reports describe their use with Crohn's
      disease. PATIENTS AND METHODS: Over a 2-year period, 31 selected patients with
      Crohn's disease underwent laparoscopic intestinal surgery: 18 women and 13 men,
      with a median age of 39 years (range 22 to 79). Indications for operation
      included: primary terminal ileitis (13); recurrent ileitis (2); Crohn's colitis
      (3); rectovaginal fistula (6); and severe perianal disease (7). Resections were
      laparoscopically assisted with division of mesentery and anastomosis performed
      extracorporeally. Diversion procedures were performed using a two-cannula
      technique. RESULTS: Twenty-five of 31 procedures were completed laparoscopically:
      loop ileostomy or colostomy (12); ileocecectomy (10); segmental colon resection
      (2); and total abdominal colectomy with ileorectal anastomosis (1). Six cases
      were converted to conventional surgery secondary to extensive adhesions from
      prior surgery (2) or severe inflammation (4). No case was converted because of
      intraoperative complication. Median operative time for diversion procedures was
      53 minutes (range 20 to 90) and for resections 195 minutes (range 90 to 380).
      Median blood loss was 100 mL (range 10 to 500), and there were no intraoperative
      complications. Only 1 postoperative complication occurred: a myocardial
      infarction. Median times to passage of flatus and bowel movement were both 3 days
      (range 1 to 6). Median time to discharge was 6 days (2 to 21) for diversion
      patients, and 6 days (3 to 7) for resected patients. CONCLUSIONS: Laparoscopic
      intestinal surgery, both for resection and diversion, is feasible and safe for
      the management of selected patients with Crohn's disease. To determine if real
      advantages exist for laparoscopy in the surgical treatment of Crohn's disease,
      further study is needed.

PMID- 8554152
TI  - How safe is strictureplasty in the management of Crohn's disease?
AB  - BACKGROUND: Strictureplasty is a well-accepted technique in the management of
      selected patients with Crohn's disease. To determine the safety and optimal
      clinical setting for performing strictureplasty, perioperative complications and
      long-term outcomes need to be analyzed. PATIENTS AND MATERIALS: We
      retrospectively reviewed the charts of 162 patients (87 men, 75 women) with
      Crohn's disease who underwent strictureplasty between June 1984 and July 1994.
      Medical and surgical history, including medications and laboratory data,
      intraoperative findings, perioperative complications, and long-term follow-up
      data were recorded. RESULTS: These patients underwent 698 strictureplasties
      (Heineke-Mikulicz procedures, 617; Finney procedures, 81). Median hospital stay
      was 8 days. Perioperative septic complications were noted in 8 patients (5%);
      however, reoperation for sepsis was needed only in 5 patients. Five percent of
      patients developed prolonged ileus after strictureplasty. Symptomatic improvement
      after strictureplasty was achieved in 98% of patients. Restricture or new
      stricture or perforative disease was seen in 5% and 17% of patients,
      respectively, during a 42-month median follow-up period. CONCLUSIONS: Our
      findings show that strictureplasty is a good surgical option for stenosing small
      bowel Crohn's disease, particularly in patients with multiple obstruction and in
      those vulnerable to short-bowel syndrome. Perioperative complications are few,
      and long-term results are gratifying.

PMID- 8554153
TI  - Pancreas-sparing duodenectomy for infra-ampullary duodenal pathology.
AB  - BACKGROUND: Surgical management of distal duodenal pathology is challenging
      because of the duodenum's retroperitoneal location and its shared blood supply
      with the pancreas. For infra-ampullary pathology, surgical treatment may include
      local excision, pancreaticoduodenectomy, or pancreas-sparing duodenectomy (PSD).
      PATIENTS AND METHODS: We retrospectively reviewed the management of 24 patients
      with infra-ampullary duodenal pathology treated by PSD between 1985 and 1994 at
      The Johns Hopkins Hospital. RESULTS: There were 16 men and 8 women with a mean
      age of 51.2 +/- 4.4 years. The indications for elective PSD in 19 patients were
      neoplasms (n = 15), Crohn's disease (n = 2), and other (n = 2). Of the neoplasms,
      13 were malignant (11 adenocarcinoma, 1 lymphoma, 1 liposarcoma) and 2 were being
      (1 villous adenoma, 1 benign stromal tumor). Five patients had PSD as an
      emergency procedure for penetrating trauma. The mean follow-up is 24.2 +/- 5.8
      months (range 1 to 122). In the group undergoing elective PSD, the mean length of
      operation was 5.3 +/- 0.4 hours, and the estimated blood loss was 569 +/- 121 mL.
      In the entire series, there was 1 postoperative death from an anastomotic leak
      and 1 reexploration for anastomotic bleeding. Pancreas-sparing duodenectomy in
      patients with trauma or benign duodenal pathology resulted in a good outcome in
      all. In those 11 patients with duodenal adenocarcinoma, 7 have died, 2 have had
      recurrences, and 2 are disease free. Actuarial and disease-free, 2-year survival
      rates in the 11 patients with duodenal adenocarcinoma were 33% and 14%,
      respectively. CONCLUSIONS: Pancreas-sparing duodenectomy is a safe and effective
      treatment in patients with distal duodenal benign neoplasms or trauma, and PSD
      appears to have limited effectiveness for malignant distal duodenal pathology.

PMID- 8554154
TI  - Awake epidural anesthesia is associated with improved natural killer cell
      cytotoxicity and a reduced stress response.
AB  - BACKGROUND: Laparotomy under general anesthesia is associated with depressed
      natural killer cell cytotoxicity (NKCC) and compromised clearance of tumor cells.
      We tested the hypothesis that awake epidural anesthesia (AEA) improves NKCC
      compared to conventional general endotracheal anesthesia (GEA). PATIENTS AND
      METHODS: Preoperative, perioperative, and postoperative (day 3) NKCC, plasma
      epinephrine, norepinephrine, cortisol levels, and 24-hour urinary cortisol levels
      were measured in 20 patients undergoing open colectomy under either AEA or GEA.
      RESULTS: Preoperative and postoperative measurements were not significantly
      different in the two groups. Patients receiving GEA had a significant reduction
      in NKCC from 36% +/- 4% preoperatively to 22% +/- 4% perioperatively (P = 0.02).
      Patients receiving AEA had no significant change in NKCC. Perioperative plasma
      epinephrine and cortisol levels were higher with GEA than AEA. The perioperative
      24-hour urinary cortisol excretion values were significantly higher in the group
      receiving GEA, suggesting a greater stress hormone response in this group
      compared to AEA patients. CONCLUSIONS: Compared to GEA, AEA appears to preserve
      perioperative NKCC. This effect may be related to an attenuated stress hormone
      response associated with AEA. Cancer patients may have improved killing of
      embolized tumor cells during surgery performed under AEA.

PMID- 8554155
TI  - The weight reduction operation of choice: vertical banded gastroplasty or gastric
      bypass?
AB  - BACKGROUND: Despite important advances in the field of bariatric surgery over the
      last 40 years, no single operation has clearly emerged as the optimum procedure.
      Over the last decade, however, attention has focused on vertical banded
      gastroplasty (VBG) and Roux-en-Y gastric bypass (RGB). PATIENTS AND METHODS: We
      compared 329 VBG procedures consecutively performed in 328 patients, and 623 VBG
      RGB operations in 560 patients for mortality, early and late complications
      requiring reoperation, and for weight loss up to 5 years. In 272 VBG-RGB
      operations, the gastric segments were stapled in continuity, and in 351 cases,
      the gastric segments were stapled and completely separated. RESULTS: Early
      complications were few for both procedures. Unsatisfactory weight loss was the
      most frequent late complication among VBG patients, whereas revision for staple
      line disruption was the most common cause for late reoperation in the VBG-RGB
      group. The incidence of stapleline disruption was 22% for VBG-RGB patients when
      gastric segments were stapled in continuity and 2% when gastric segments were
      completely divided (P < 0.0001). Weight loss for the VBG patients and VBG-RGB
      patients at 5 years was 47% and 62%, respectively (P < 0.0001). CONCLUSION: Our
      data suggest, as others have shown, that RGB is a better weight-loss operation
      than VBG. A lesser curvature vertical pouch stapled in continuity with the
      excluded stomach can be associated with a high rate of staple-line disruption in
      RGB. Separation of gastric segments appears to significantly diminish this
      complication (P < 0.0001). Late complications now are fewer, and VBG-RGB is our
      weight-reduction procedure of choice.

PMID- 8554156
TI  - Greater risk of incisional hernia with morbidly obese than steroid-dependent
      patients and low recurrence with prefascial polypropylene mesh.
AB  - BACKGROUND: Incisional hernia is a serious complication of abdominal surgery. We
      compared incisional hernia frequency following gastric bypass (GBP) for morbid
      obesity versus total abdominal colectomy and ileal pouch-anal anastomosis (IPAA)
      for ulcerative colitis. A prefascial polypropylene mesh repair was also
      evaluated. PATIENTS AND METHODS: All patients had midline incisions, xiphoid to
      umbilicus in GBP patients and midepigastrium to pubis in IPAA patients. Fascia
      were closed with running No. 2 polyglycolic acid suture. Ninety-eight patients
      underwent prefascial polypropylene mesh repair; 80 were GBP patients, 46 had 1
      previous repair, and 17 had 2 to 9 previous repairs (6 with properitoneal mesh).
      RESULTS: Incisional hernia occurred in 20% (198/968) of GBP patients (19% without
      versus 41% with a previous hernia, P < 0.001) versus 4% (7/171) of the IPAA
      patients (P < 0.001), of whom 102 (60%) were taking prednisone (32 +/- 2 mg/d)
      and 5 were quite obese (body mass index > or = 30 kg/m2). Additional risk factors
      for hernia in GBP patients included wound infection, diabetes, sleep apnea, and
      obesity hypoventilation. For the 98 patients who underwent prefascial
      polypropylene mesh repair, the mean follow-up was 20 +/- 2 months (range 6 to
      104), and complications occurred in 35% of patients, including minor wound
      infection (12%), major wound infection (5%), seroma (5%), hematoma (3%), chronic
      pain (6%), and recurrent hernia (4%). CONCLUSIONS: Severe obesity is a greater
      risk factor for incisional hernia and hernia recurrence than chronic steroid use
      in nonobese colitis patients. A prefascial polypropylene mesh repair minimizes
      recurrence.

PMID- 8554157
TI  - Salsalate, morphine, and postoperative ileus.
AB  - BACKGROUND: Previously, we demonstrated that ketorolac, a nonsteroidal
      antiinflammatory drug (NSAID), prevented postoperative small bowel ileus in a
      rodent model. The aim of this study was to evaluate the effect of salsalate, an
      NSAID without antiplatelet effect, on postoperative ileus alone or in combination
      with morphine. METHODS: Forty-eight rats underwent placement of duodenal
      catheters and were then randomly assigned to one of eight groups (n = 6). Four
      groups had standardized laparotomy following drug administration, whereas 4
      groups underwent the same treatment without laparotomy: control and morphine
      animals received 0.1 mL alcohol via the catheter, whereas salsalate and salsalate
      plus-morphine animals received salsalate (15 mg/kg) dissolved in 0.1 mL alcohol.
      The animals also received 0.5 mg/kg morphine (morphine and salsalate plus
      morphine) or the same volume of saline (control and salsalate) subcutaneously.
      Transit was measured following the injection of a nonabsorbed marker via the
      duodenal catheter and is defined as the geometric center (GC) of distribution. An
      additional 20 rats had serosal electrodes placed on the jejunum, and were
      assigned to one of four treatment groups (control, salsalate, morphine, and
      salsalate plus morphine; n = 5 each group). Myoelectric activity was recorded
      until the reappearance of the migrating myoelectric complex (MMC) following
      laparotomy. RESULTS: Laparotomy and morphine independently reduced small bowel
      transit (P = 0.0006 and 0.006, respectively, by three-way analysis of variance
      [ANOVA]; GC 4.3 +/- 0.2 control versus 2.2 +/- 0.3 laparotomy versus 3.6 +/- 0.4
      morphine), but morphine did not further worsen postoperative transit (GC 2.4 +/-
      0.4; P = 0.42). Although salsalate did not alter baseline transit, pretreatment
      improved postoperative transit (P = 0.0002; GC 3.6 +/- 0.4). This effect was lost
      with the addition of morphine (GC 2.7 +/- 0.2; P = 0.21). The MMCs returned
      earlier after laparotomy in salsalate-pretreated rats (63 +/- 18 minutes
      salsalate versus 160 +/- 12 minutes laparotomy; P < 0.01, one-way ANOVA).
      However, this effect was also lost in animals receiving morphine (106 +/- 16 min;
      P > 0.05). CONCLUSION: Salsalate improves postoperative small bowel motility in a
      rodent model; however, this effect is masked by morphine.

PMID- 8554158
TI  - Delayed gastroduodenal emptying is an important mechanism for control of
      intestinal transit in short-gut syndrome.
AB  - PURPOSE: To understand the relative importance of changes in ileal smooth muscle
      contractility versus alteration of intestinal flow rate as control mechanisms for
      regulating intestinal transit in a surgical model of short-gut syndrome. METHODS:
      A model of short-gut syndrome was created by performing a 70% proximal small
      bowel resection in dogs. Ten control and 6 animals with short-gut syndrome were
      instrumented with strain gauge transducers, steel collection cannulas, and a
      Silastic intraluminal infusion catheter in the midileum. Motor activity was
      analyzed by computer programs that determine frequency, amplitude, and
      propagation behavior of postprandial contractions. Perfusions of 14C-polyethylene
      glycol and bolus injection of 3H-polyethylene glycol were used to determine
      intestinal flow and transit rates. Total gastroduodenal emptying was determined
      using a 14C-polyethylene glycol-labelled meal. RESULTS: Postprandial contraction
      frequency was decreased in animals with short-gut syndrome, but other significant
      changes in amplitude, mean area, and propagation behavior of postprandial ileal
      contractions were not seen. Gastroduodenal emptying and mean intestinal flow
      rates were markedly slower in animals with short-gut syndrome, as were intestinal
      transit rates. CONCLUSIONS: In this model of short-gut syndrome, the major
      adaptive change is decreased intestinal flow rate, related to delayed
      gastroduodenal emptying. The spatial organization of ileal contractions does not
      change substantially aside from a change in frequency which can be accounted for
      by transection of the intestinal wall.

PMID- 8554159
TI  - Pyruvate prevents ischemia-reperfusion mucosal injury of rat small intestine.
AB  - BACKGROUND: Since reactive oxygen intermediates (ROI, or free radicals) have been
      implicated in the pathogenesis of ischemia-reperfusion injury of the small bowel,
      we evaluated the pretreatment effect of pyruvate, a 3-carbon compound recently
      shown to inhibit superoxide production, on reperfusion mucosal injury in the rat.
      METHODS: The small bowel of the ACI rat (n = 6) was divided into 2 5-cm segments,
      and 10 mL of a liquid diet containing pyruvate (0.32 g) or placebo (0.26 g) was
      instilled into the lumen of one of the segments for 10 minutes. The bowel was
      then made completely ischemic for 45 minutes by clamping the superior mesenteric
      artery, which was followed by 60 minutes of reperfusion. RESULTS: The production
      of ROI in bowel biopsy samples, estimated by luminol-enhanced chemiluminescence,
      was at least 80% decreased in the segment containing pyruvate compared with
      placebo immediately after ischemia (time 0), and compared with 30 and 60 minutes
      of reperfusion (P < 0.05 for each time point). After 60 minutes of reperfusion,
      the bowel segment containing the placebo diet showed villus sloughing with
      destruction of lamina propria and crypts, and mucosal neutrophil infiltration had
      increased by 80%. Electron microscope evaluation revealed a reduction in number
      and size of microvilli, dilatation of intercellular spaces, and intracellular
      vacuoles. The bowel segment containing pyruvate showed the villi and crypts to be
      intact, without enhanced neutrophil infiltration. CONCLUSION: Pyruvate
      pretreatment of the rat small bowel inhibits postischemic reperfusion mucosal
      histologic injury, neutrophil infiltration, and ROI production.

PMID- 8554160
TI  - Piezoelectric immunosensor for the detection of immunoglobulin M.
AB  - A piezoelectric immunosensor has been developed for the determination of human
      IgM. The crystals are AT-cut and have a basic resonant frequency of 9 MHz.
      Immobilization of goat antihuman IgM antibodies to the crystals' surfaces was
      accomplished via a CNBr-activated copolymer coating of 2-hydroxyethyl
      methacrylate and methylmethacrylate. The IgM piezoelectric immunosensor can be
      used for the human IgM determination in the range 5-93 micrograms ml-1. The
      analytical results given by this approach were in satisfactory agreement with
      those given by the single radical immunodiffusion procedure. The sensitivity,
      specificity and reproducibility of this immunosensor were investigated. Further,
      the valent value of goat antihuman IgM antibody binding with human IgM antigen
      and the affinity constant of immunoreaction in this experimental system were
      studied. After washing with tetrahydrofuran, a crystal can be re-used 20 times
      without detectable loss of sensitivity.

PMID- 8554161
TI  - Evaluation of ractopamine cross-reactivity in several commercially available beta
      agonist enzyme immunoassay kits.
AB  - Several enzyme immunoassay test kits are commercially available for screening of
      matrices including cattle feed, tissues, faeces and urine for the presence of
      beta-agonists. The kits utilized for this evaluation offer sensitivity as low as
      0.1 ng ml-1 (assay solution concentration, not test sample). Evaluation of
      ractopamine hydrochloride (LY31537) solutions at concentrations as high as 1000
      ng ml-1, using six different kits from four different manufacturers, showed cross
      reactivity of less than 0.5%.

PMID- 8554163
TI  - Does the paraxial mesoderm of the avian embryo have hemangioblastic capacity?
AB  - In a previous study of the hemangioblastic capacity of lateral plate mesoderm, we
      showed that the endoderm-associated splanchnopleural layer is capable of giving
      rise to both endothelial and hemopoietic cells while the ectoderm-associated
      somatopleural layer is not (Pardanaud and Dieterlen-Lievre 1993a). In order to
      complete the inventory of territories able to produce these two cell lineages, we
      assayed the paraxial mesoderm, and report the results here. Quail somites or
      segmental plates were treated with mab QH1+complement in order to eliminate
      attached aortic endothelial cells, which cling to the ventral aspects of these
      structures. They were grafted in the limb bud or the coelom of chick host, since
      these sites promote the differentiation of endothelial and hemopoietic cells,
      respectively. Vascular development and hemopoietic cell emergence were analyzed
      using QH1 immunocytology. Segmental plate and somites both produced abundant
      endothelial cells. In addition, the segmental plate gave rise to small groups of
      hemopoietic cells when grafted in the coelom.

PMID- 8554162
TI  - Lymphocytes in the lung: an often neglected cell. Numbers, characterization and
      compartmentalization.
AB  - The lung is continuously in contact with inhaled particles, some of which are of
      microbial origin. This requires adequate defence mechanisms in the form of immune
      reactions. These can be subdivided into the afferent and efferent limb. Specific
      immune reactions depend on the interactions between lymphoid and accessory cells.
      Therefore, the local histotopographic localization of lymphocyte subsets has to
      be known to understand pulmonary immune reactions. As lymphocytes have often not
      been mentioned when cells in the respiratory tract have been characterized, their
      compartmentalization, number and subset composition in the lung are outlined
      here. Lymphocytes are found in the epithelium and lamina propria of the bronchi
      with different subset compositions. In some species, like the rabbit, bronchus
      associated lymphoid tissue (BALT) is found as follicle-like aggregations with
      lymphocytes infiltrating the epithelium, which shows specialized epithelial
      cells. BALT, however, is not a constitutive structure in all species, e.g. in
      humans. Nevertheless, certain (probably) microbial stimuli can induce BALT in
      adult humans. In contrast to many other organs, the lung vascular bed contains
      large numbers of lymphocytes. Little is known about the adhesion molecules that
      make this margination possible. In the lung interstitium about 10 x 10(9)
      lymphocytes have been calculated for healthy adults. The most easily accessible
      pool of lymphocytes in the human lung are those recovered by bronchoalveolar
      lavage. The vast majority of such lymphocytes express markers typical for "memory
      lymphocytes". The intrapulmonary migratory routes of lymphocytes and the
      integration of the lung in the common mucosal immune system are
      described.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554164
TI  - A developmental study of the synovial membrane of the rat temporomandibular
      joint: changes in the three-dimensional configuration during postnatal
      development.
AB  - The development of synovial membranes in the posterior synovial portion of the
      rat temporomandibular joint was studied and the three-dimensional structure of
      the posterior synovial portion reconstructed from sagittal semithin sections.
      Reconstructions showed that the synovial membrane expanded and that synovial
      folds increased in number and became complicated in shape with the growth of the
      joint. Using transmission-electron microscopy, it was observed that the synovial
      lining cells degenerated, that the synovial membrane split to make further
      synovial folds, and that the folded-end structures consisted of synovial lining
      cells that extended into the subsynovial connective tissue. It is suggested that
      in the development of the three-dimensional configuration of the synovial
      membrane, several processes proceed simultaneously to form the synovial folds: a
      splitting of the synovial membrane, infolding of the synovial membrane into the
      subsynovial connective tissue, and outgrowth of the synovial folds towards the
      synovial cavity.

PMID- 8554165
TI  - G-protein activation enhances Ca(2+)-dependent lipid secretion of the rat
      harderian gland.
AB  - We studied the secretory mechanism of the Harderian gland of rats. After
      perfusion with HEPES-buffered Ringer's solution containing NaF (10 mM) with AlCl3
      (10 microM), a G-protein activator, the glandular cells of the Harderian gland
      showed massive exocytosis and apocrine-like protrusions on the luminal surface.
      Some of the secretory vacuoles aggregated within the cytoplasm, and large
      vacuoles were formed. Contraction of the myoepithelial cells covering the
      glandular endpieces caused a narrowing of the glandular lumina, which contained
      cytoplasmic fragments, and deformation of the basal contour of the glandular end
      pieces. The basal regions of the glandular cells also bulged between the
      myoepithelial cells. Secretory vacuoles were also discharged to the lateral cell
      surface, and the intercellular spaces were dilated. The enhanced secretory
      activities of the glandular cells and the contraction of the myoepithelial cells
      were similar to those in rats stimulated with 10 microM carbachol (CCh). However,
      dilatation of the endoplasmic reticulum in glandular cells (type A cells), which
      leads to the formation of small vesicles, was observed in those glands stimulated
      by NaF+AlCl3, but not in those stimulated by CCh. Removal of Ca2+ from the
      perfusing HR or addition of EDTA (0.5 mM) diminished and inhibited NaF+AlCl3- or
      CCh-enhanced secretory activity of the glandular cells and also allayed the
      deformation of glandular cells caused by myoepithelial cell contraction. The
      present results demonstrate the involvement of G-proteins and Ca(2+)-influx in
      the lipid secretion of glandular cells and in the contraction of myoepithelial
      cells of the Harderian gland in rats.

PMID- 8554166
TI  - Localization of type I and II collagen during development of human first rib
      cartilage.
AB  - The localization of fibrillar type I and II collagen was investigated by
      immunofluorescence staining with specific antibodies in order to obtain a better
      understanding of tissue remodelling during the development of first rib
      cartilage. In childhood and early adolescence type I collagen was found to be
      restricted to the perichondrium of first rib cartilage, while type II collagen
      was localized in the matrix of hyaline cartilage. However, in advanced age type I
      collagen was also found in the territorial matrix of intermediate and central
      chondrocytes of first rib cartilage. The matrix of subperichondrial chondrocytes
      was negative for type I collagen. This suggests that some chondrocytes in first
      rib cartilage undergo a modulation to type I collagen-producing cells. The first
      bone formation was observed in rib cartilages of 20- to 25-year-old adults.
      Interestingly, the ossification began peripherally, adjacent to the innermost
      layer of the perichondrium where areas of fibrocartilage had developed. The newly
      formed bone matrix showed strong immunostaining for type I collagen.
      Fibrocartilage bordering peripherally on bone matrix revealed only a faint
      staining for type I collagen, but strong immunoreactivity to type II collagen.
      The interterritorial matrix of the central chondrocytes failed to react with the
      type II collagen antibody, in both men and women, from the end of the second
      decade. These observations indicate that major matrix changes occur at the same
      time in male and female first rib cartilages. Thus, our findings indicate that
      ossification in human first rib cartilage does not follow the same pattern as
      that observed in endochondral ossification of epiphyseal discs or sternal
      cartilage.

PMID- 8554167
TI  - Cholinergic projections to the anterior thalamic nuclei in the rat: a combined
      retrograde tracing and choline acetyl transferase immunohistochemical study.
AB  - Retrograde transport of horseradish peroxidase (HRP) was combined with choline
      acetyltransferase (ChAT) immunohistochemistry to study cholinergic projections to
      the anterior thalamic nuclei in the rat. Small iontophoretic injections of HRP
      placed into different subdivisions of the anterior thalamic nuclear complex
      resulted in distinct patterns of retrograde labelling in two major cholinergic
      cell groups of the mesopontine tegmentum, the laterodorsal tegmental nucleus
      (LDTg), in which a majority of the labelled cells was located, and the
      pedunculopontine tegmental nucleus (PPT). After injections into the posterior
      subdivision of the anteroventral thalamic nucleus (AVp), double-labelled neurons
      were present predominantly in the ipsilateral LDTg while a smaller number was
      found in the PPT. In the ipsilateral LDTg, 60-70% of ChAT-positive neurons were
      HRP-labelled, and 90-95% of the HRP-labelled neurons were ChAT-positive. In the
      contralateral LDTg, 30-40% of ChAT-positive neurons were HRP-labelled. After
      injections in the medial subdivision of the anteroventral thalamic nucleus (AVm),
      the pattern of labelling in LDTg was similar to that detected after injections in
      the AVp. The number of double-labelled neurons in the LDTg and PPT was much lower
      after injections into AVm than after injections into AVp. When injections were
      confined to the anterodorsal thalamic nucleus (AD), no HRP-labelled cells were
      present in the LDTg or PPT. These results show that the LDTg and PPT are the
      sources of the cholinergic input to the rat anterior thalamus. The major
      projection from LDTg and PPT is to the AVp, whereas there is a lighter
      cholinergic projection to the AVm. The AD does not receive a projection from
      cholinergic cells in the mesopontine tegmentum.

PMID- 8554168
TI  - Morphological alterations of hippocampal pyramidal neurons heterotopically
      transplanted into the somatosensory cortex of adult rats: a quantitative Golgi
      study.
AB  - A characteristic feature of hippocampal organization is the laminated termination
      of extrinsic and intrinsic afferents. At present, it is not known to what extent
      these layer-specific fiber projections modulate the development and final shape
      of the dendritic arbor of hippocampal target neurons. In the present study,
      pieces of late embryonic (E18) rat hippocampus were transplanted heterotopically
      into a cavity in the somatosensory cortex of 6-8 week-old recipient rats. Here,
      the transplanted neurons differentiated and survived up to several months in the
      absence of their specific extrinsic afferents. Moreover, tracing of transplant
      connections with the carbocyanine dye DiI revealed only a limited projection
      between the transplant and the host neocortex. Golgi-impregnated transplants were
      used to analyze the postsynaptic structures (dendrites and spines) of hippocampal
      pyramidal cells quantitatively. Compared with controls, the transplanted
      pyramidal neurons showed a significant reduction of apical primary dendrites and
      basal dendritic branches, i.e. of peripheral dendritic portions that originate
      farther from the soma. In contrast, the number of basal primary dendrites
      originating directly from the perikaryon was enhanced. Spine density on the main
      apical dendritic shaft was significantly lower in all peripheral dendritic
      segments in transplanted neurons. We conclude from our results that the absence
      of layer-specific extrinsic afferents that normally terminate on peripheral parts
      of the dendritic arbor of hippocampal pyramidal neurons caused a reduction of
      these peripheral dendrites and spines. In contrast, the increase of dendrites and
      spines near the cell body might be induced by intrinsic fibers that normally
      terminate on these proximal dendritic portions and are known to sprout under
      transplant conditions.

PMID- 8554169
TI  - The urokinase plasminogen activator (u-PA) and its inhibitor (PAI-1) in embryo
      fetal bone formation in the human: an immunohistochemical study.
AB  - The role of urokinase plasminogen activator and plasminogen activator inhibitor-1
      in human embryo-fetal bone formation between the 9th and the 20th week of
      gestation has been studied immunohistochemically. While mature osteocytes of the
      secondary spongiosa and resting chondrocytes of the bone epiphyses were negative
      for both antigens in each developmental stage, metabolically active parts of the
      osseocartilaginous system showed a strong immunoreactivity. Until the end of the
      10th week of gestation urokinase plasminogen activator and plasminogen activator
      inhibitor-1 could not be demonstrated in the shaft of the preexisting
      cartilaginous models of bones, which correlates with the morphological
      developmental stage of the embryos. Later, osteoblasts and chondrocytes in the
      areas of enchondral ossification, and the perivascular chondrocytes of the
      epiphyseal secondary ossification centres, showed similarly high concentrations
      of urokinase plasminogen activator and plasminogen activator inhibitor-1.
      Moreover, the individual ossification stages of the different bones in embryo
      fetal development could be demonstrated immunohistochemically. While humeri and
      femora showed diaphyseal immunoreactivities at an early stage, positive reactions
      in the phalanges were found only much later. Thus, the enzymes of the
      fibrinolytic system studied are clearly involved in the desmal and enchondral
      ossification process in the osseocartilaginous compartment.

PMID- 8554171
TI  - Organization and cytology of lymphoid tissue in the cynomolgus monkey
      conjunctiva.

PMID- 8554170
TI  - Postnatal development of calbindin-D28k immunoreactivity in the cerebral cortex
      of the cat.
AB  - To learn about maturational patterns of nonpyramidal neurons in the cerebral
      cortex, calbindin-D28k immunoreactivity was studied in the kitten cortex.
      Immunoreactive neurons first appear in the cortical and subcortical areas related
      to the limbic system, including the cingulate and retrosplenial cortices, and in
      the secondary motor areas. These are followed by the primary motor and sensory
      association areas and, finally, by the primary sensory areas. In all cortical
      areas, calbindin-D28k immunoreactivity first develops in layer V pyramidal
      neurons and later in nonpyramidal neurons, except in the primary sensory areas,
      where immunoreactive pyramidal neurons are not found at any age. Transient
      calbindin-D28k immunoreactivity occurs in pyramidal neurons that are mainly
      localized in the cingulate and retrosplenial cortices and in the secondary motor
      area, as well as in nonpyramidal neurons localized in the subplate and layer I,
      and in a subset of large multipolar and bitufted neurons in layer VI.
      Nonpyramidal neurons localized in layers II to IV, and some neurons in layer VI,
      develop permanent calbindin-D28k immunoreactivity. Calbindin-D28k
      immunoreactivity labels subsets of GABAergic interneurons that form vertical
      axonal tufts, so that temporal and regional patterns of calbindin-D28k
      immunoreactivity during development may be implicated in the maturation of
      columnar (vertical) inhibition in the cerebral cortex. In addition to neurons,
      corticofugal and afferent fibres of subcortical origin exhibit calbindin-D28k
      immunoreactivity. Transient calbindin-D28k immunoreactivity occurs in
      corticofugal fibres arising from the cingulate and prefrontal cortices, which are
      probably corticostriatal projection fibres. In contrast, permanent
      immunoreactivity occurs in what are probably thalamocortical fibres ending in
      layer IV, and in punctate terminals located in the upper third of layer I.

PMID- 8554172
TI  - Cytoskeletal architecture of rat calvarial osteoclasts: microfilaments, and
      intermediate filaments, and nuclear matrix as demonstrated by detergent
      perfusion.

PMID- 8554173
TI  - Bone histomorphometric changes in the femoral neck of aging and ovariectomized
      rats.

PMID- 8554174
TI  - Architecture of the synovial vasculature in rabbit knee joints studied by
      scanning electron microscopy.

PMID- 8554175
TI  - Quantitative microscopic changes in the mole rat testes during an annual cycle.

PMID- 8554176
TI  - Morphological evidence of exocrine function in coagulating gland renin of mouse
      strain C57BL/6.

PMID- 8554177
TI  - Ultrastructural quantitative analysis of the innervation of axillary lymph nodes
      of the rat after antigenic stimulation.

PMID- 8554178
TI  - Ultrastructural quantitative analysis of the innervation of axillary lymph nodes
      in juvenile and old rats.

PMID- 8554179
TI  - Ontogeny of sensory nerves in the developing skeleton.

PMID- 8554180
TI  - Integrin distribution during heart development in the long-tailed macaque (M.
      fascicularis).

PMID- 8554181
TI  - Thyroid gland development in the brushtail possum, Trichosurus vulpecula.

PMID- 8554182
TI  - Immunolocalization of N-CAM in the heart of the early developing rat embryo.

PMID- 8554184
TI  - International Anesthesia Research Society 70th Clinical and Scientific Congress.
      Washington, D.C., March 8-12, 1996. Abstracts.

PMID- 8554183
TI  - Calcium-binding proteins in avian herbst and grandry sensory corpuscles.

PMID- 8554185
TI  - Physics and principles of breast ultrasound.
AB  - Ultrasound refers to sound of any frequency greater than 20 kilohertz; that is,
      above the frequency for which humans can normally hear. All sound, including
      ultrasound, travels through different tissues at different rates of speed. The
      point at which adjacent tissues with different speeds of sound meet is referred
      to as an acoustic interface. When sound hits an acoustic interface, an echo is
      created. Medical ultrasound is essentially a means of producing visual images
      based on echoes that occur at such acoustic interfaces. Crystals within the
      ultrasound transducer are capable of generating and receiving sound waves based
      on the "piezo-electric" effect. By this effect, the mechanical energy of the echo
      is converted into electrical energy that can be imaged on the ultrasound monitor.
      The resolution of ultrasound images of the breast has been greatly improved by
      computer-enhancement capabilities and the availability of high-frequency
      transducers. Although the detailed imaging of modern ultrasound allows for
      satisfactory evaluation of most breast lesions, there are a variety of artifacts
      inherent to breast ultrasound of which one must be cognizant, so as to avoid
      misinterpretation. This article will address a number of these issues, thereby
      presenting an introduction to the basic physics and principles relevant to breast
      ultrasound.

PMID- 8554186
TI  - Breast ultrasound for surgeons.
AB  - Until recently, use of ultrasound in the breast was limited primarily to the
      differentiation of the solid versus cystic nature of nonpalpable,
      mammographically-detected masses. Advancements in ultrasound technology have
      allowed for delineation of specific ultrasonographic characteristics of breast
      masses and, as such, placement of these masses into categories based on their
      relative risk of malignancy. Depending on that relative risk, ultrasound-guided
      needle aspiration and/or core biopsy of these masses may be performed. Both
      diagnostic ultrasound and ultrasound-guided needle biopsy of the breast have been
      demonstrated to be quite accurate. These techniques may avoid many unnecessary
      open biopsies for benign lesions and facilitate therapeutic planning for
      malignant lesions.

PMID- 8554187
TI  - Bringing core biopsy into a surgical practice.
AB  - Minimally invasive diagnostic techniques in evaluating patients with breast
      disease have been increasingly utilized and accepted by physicians and patients
      over recent years. The incorporation of stereotactic core needle biopsy and
      ultrasound-guided core needle biopsy into the office practice of evaluating
      patients with breast disease by our surgical faculty has been met favorably.
      These procedures are readily learned by surgeons. The judicious use of these
      procedures is evidenced by the malignancy rate of core biopsies of 16 per cent,
      identical to the historical rate for needle localization assisted excisional
      biopsy at our institution. Core breast biopsy expedites definitive diagnosis and
      optimizes patient convenience. Reimbursement is highly variable, and active
      physician participation in negotiating with payors to insure that costs are met
      is essential.

PMID- 8554188
TI  - Stereotactic uses beyond core biopsy: model development for minimally invasive
      treatment of breast cancer through interstitial laser hyperthermia.
AB  - Light of a Nd:YAG laser presented through a fiberoptic cable to a diffusing tip
      can be adapted to mammographic stereotactic instruments now used for core biopsy
      in the hyperthermic endoablation of breast cancer. This approach to cancer
      destruction extends breast preservation to the point of no observable surface
      skin change. The initial analysis characterizes the effects of laser
      endohyperthermia in a physical model as well as in tissue, both ex vivo and in
      vivo, to create a reliable technique that will lead to human trials. A fiberoptic
      cable with a diffusing quartz tip placed deep within soft tissue can pass light
      of a neodymium laser and consequent thermal energy for the destruction of
      surrounding soft tissues. Because breast cancer occurs with greatest frequency in
      the involuted breasts of women more than 50 years of age and because this tissue
      is predominantly fibro-fatty in nature, our work has concentrated on model
      development and the determination of heat distribution and destruction of fat and
      fibro-fatty tissue. Following the development of a physical model, time
      temperature courses were found to be similar in ex vivo human breast tissue and
      subcutaneous porcine fat. This led to in vivo porcine studies that confirmed
      similar time-temperature courses. For tissues brought to a range of 60 degrees C
      to 80 degrees C and sustained for the better part of 20 minutes, gross and
      histological analyses reveal complete destruction over a 1 1/2 cm radial region
      around the laser tip. This approach offers great promise for the treatment of
      stereotactically biopsied small T1 breast carcinomas.

PMID- 8554189
TI  - Management of nipple discharge.

PMID- 8554190
TI  - Physical, psychological, and economic advantages of accelerated discharge after
      surgical treatment for breast cancer.
AB  - The economic benefits of outpatient surgery and of short hospital stay have been
      amply emphasized over the past 5 years. The economic, physical, and psychological
      benefits of such an approach for treating patients with early breast cancer are
      detailed in this report. Of 208 patients treated by the author over a 3-year
      period (1991-1993), 63 (30.3%) were treated on an outpatient basis. Of 132
      patients undergoing axillary node dissection, 29 (21.9%) were sent home the day
      of operation, and 95 (72%) stayed in the hospital overnight. The median number of
      lymph nodes removed was 17 and the median length of stay for all patients was one
      day; 31.8 per cent of these patients developed seromas, and 2 were readmitted for
      infected seromas. The per diem cost for our hospital in 1993 was $684. The
      program incorporates a strong institutional support component, with unlimited
      access to physicians and nurses, and has led to significant cost savings. It has
      also led to better physical and psychological recovery, emphasizing patient
      comfort, control and independence, and strong family interactions. Because 75 per
      cent of our 300 patients treated for breast cancer in our setting each year
      undergo axillary node dissection, $153,900 is expended for each day patients stay
      in our hospital, and presumably $92 million is expended country-wide. Adopting
      such a program can lead to significant savings without compromising the quality
      of care. The physical and psychological benefits of such an approach outweigh any
      minor inconveniences on patients and families.

PMID- 8554191
TI  - Stereotactic breast biopsy: its history, its present, and its future.

PMID- 8554192
TI  - Skin sparing mastectomy: anatomic and technical considerations.
AB  - Skin sparing mastectomy is a relatively new technique based on the fascial
      anatomy of the breast. It removes the breast, nipple-areola complex, previous
      biopsy incisions, and skin overlying superficial tumors. Preservation of native
      skin and the inframammary fold greatly enhances the aesthetic result of breast
      reconstruction. The operation has been adopted for patients with early breast
      cancer treated by total mastectomy and immediate reconstruction, but has received
      little attention in the general surgery literature. The anatomical and technical
      aspects of skin sparing mastectomy are described.

PMID- 8554193
TI  - Should general surgeons perform specialty procedures? An outcome experience with
      reduction mammoplasty.
AB  - Recent health care reform proposals have emphasized the need for "generalists"
      over "specialists." Particularly targeted are the "surgical specialties." If much
      of this reform comes to pass, this may leave patients for whom the only surgical
      care may come from the general surgeon. In this setting, opportunities exist for
      the general surgeon to provide services that now are claimed by surgical
      specialists. This study reports the outcome experience of one general surgeon
      providing one such procedure, reduction mammoplasty, to a beneficiary population.
      Over a 26 month period, 50 reduction mammoplasties were performed. An average of
      1527 grams of breast tissue were removed from each patient. There were no
      episodes of nipple necrosis or other complications requiring reoperation. At 1-26
      months follow-up, all patients had relief of presenting symptoms, 90 per cent of
      patients had normal nipple sensation; all patients were satisfied with the
      results and would have the operation again by the same surgeon. These results
      show that a motivated and well-trained general surgeon can provide specialty
      surgical care to a potentially underserved population. General surgeons should be
      allowed to develop and practice the full range of skills they will need to take
      advantage of the opportunities that will be available to the surgical
      "generalist."

PMID- 8554194
TI  - Axillary lymph node dissection: does it have a role in primary breast cancer?
AB  - The role of elective lymph node dissection has been increasingly questioned for
      the treatment of primary breast cancer. In an attempt to evaluate whether or not
      axillary lymph node dissection is of value in early breast cancer, a
      retrospective review of all breast cancers treated at Eisenhower Army Medical
      Center was conducted. During that time, 434 patients with breast cancer were
      treated. Eighty-six of those patients had lesions that were 2.0 cm or smaller.
      Eighty-one patients underwent axillary lymph node dissection. Twenty-four
      patients were found to have positive axillary nodes (28%). If the patients were
      further divided into those with lesions 1.0 centimeters or less versus 1.1-2.0
      cm, the incidence of node positivity was 19 per cent and 35 per cent,
      respectively. Of the patients who underwent axillary lymph node dissection, 60
      per cent of those whose lymph nodes were negative received no further treatment,
      whereas those whose lymph nodes were positive received additional therapy 92 per
      cent of the time. An additional 8 per cent of the node-negative patients received
      radiation therapy as the only added therapy after segmental mastectomy with
      axillary lymph node dissection. Our study demonstrates, or at least suggests,
      that node positivity did influence subsequent therapy. In addition, the
      relatively high incidence of positive axillary nodes (28%) in these early breast
      cancers supports the potential therapeutic benefit of axillary node dissection.

PMID- 8554195
TI  - The stability of estrogen and progesterone receptors in patients receiving
      preoperative chemotherapy for locally advanced breast carcinoma.
AB  - The determination of estrogen (ER) and progesterone receptor (PR) content is
      routine in the management of carcinoma of the breast. Such data are commonly used
      to predict responses to endocrine therapy. Preoperative chemotherapy is often
      utilized in the treatment of patients with locally advanced carcinoma of the
      breast. However, little attention has been focused upon the effect of
      preoperative chemotherapy on hormonal receptor expression in that setting. The
      purpose of this study is to evaluate the effect of preoperative chemotherapy on
      ER and PR expression in patients with locally advanced breast carcinoma. Patients
      with T3 or T4 adenocarcinoma of the breast from Charity Hospital in New Orleans
      were studied. Levels of ER and PR were determined from tissue blocks obtained at
      diagnostic biopsy, as well as after the preoperative chemotherapy. The receptor
      levels were determined using immunohistochemistry and quantified using image
      analysis. We evaluated 21 locally advanced cancer patients who received at least
      three cycles of standard chemotherpay regimens. Of these patients, 11 achieved a
      partial response, with 3 achieving a complete response after preoperative
      chemotherapy. A total of 33 per cent of patients had a significant change in
      hormonal receptor content after preoperative chemotherapy. ER changed in 17%, PR
      in 22%, and both ER and PR in 6%. These data show that ER and/or PR expression
      changed in 33% of patients studied. Further, ER and PR status does not appear to
      predict or correlate with response to chemotherapy. This suggests that
      determination of ER and PR may best be performed from definitive resection
      specimens in patients who receive preoperative chemotherapy.

PMID- 8554196
TI  - Special stereotactic breast biopsy issue.

PMID- 8554197
TI  - History of breast disease: the earliest recordings.

PMID- 8554198
TI  - The revolution in breast biopsy: where is the surgeon?
AB  - Technology is now available to significantly alter the means by which breast
      biopsies are performed. Percutaneous image guided breast biopsies (PIGBB) are
      minimally invasive, accurate, and cost effective. Clinical integration of this
      new technology has been difficult because the procedure involves both radiology
      and surgical skills. Neither the majority of general surgeons nor the majority of
      radiologists have embraced the procedure. The technology has been available in
      this country for several years, but a comfortable clinical integration has not
      been accomplished. The surgeon, with an enhancement of existing breast imaging
      skills, should be able to stay involved in breast biopsy diagnosis and
      accommodate the new biopsy technique.

PMID- 8554199
TI  - Stereotactic breast biopsy: a practical approach.
AB  - The continuing increase of women participating in mammographic screening has
      resulted in a rise in the number of nonpalpable abnormalities identified. The
      development of minimally invasive and cost-effective methods to achieve accurate
      histologic diagnosis is needed. Stereotactic needle core biopsy had been used to
      reduce the number of women requiring needle-directed open surgical biopsies for
      benign disease. The team approach is essential for implementation of these newer
      diagnostic and interventional modalities. The surgeon has always taken the
      responsibility for coordinating the diagnostic and treatment components of
      appropriate breast care. Therefore, surgeons must continue to integrate new
      technology into their practices. The extensive experience of more than 3000
      stereotactic biopsies performed at The Breast Center has provided the background
      for discussing the technical aspects of the procedure. The appropriate workup and
      subsequent indications for patient selection are reviewed. Pre and postprocedural
      patient considerations are addressed. This should provide an introduction to the
      basic principles of stereotactic needle core biopsy for implementation into a
      surgical practice.

PMID- 8554200
TI  - Exogenous insulin administration and cardiovascular risk in non-insulin-dependent
      and insulin-dependent diabetes mellitus.
AB  - PURPOSE: It is currently unknown whether intensive insulin treatment of diabetes
      decreases the risk for cardiovascular complications by lowering glucose levels or
      increases the risk by postulated direct atherogenic effects. This article reviews
      published data from two long-term, randomized clinical trials that compared
      cardiovascular outcomes associated with different exogenous insulin treatment
      regimens. STUDY SELECTION AND DATA SOURCES: The University Group Diabetes Program
      (UGDP) and the Diabetes Control and Complications Trial (DCCT) were selected as
      the only available randomized intervention trials with long-term follow-up
      results. Data reviewed were from the major publications of these two trials.
      RESULTS: The UGDP compared the effects of a fixed-dose standard insulin regimen,
      a variable-dose insulin regimen, and a diet plus oral placebo regimen in over 600
      patients with non-insulin-dependent diabetes mellitus (NIDDM) who were followed
      for up to 13 years (1962 to 1975). Plasma glucose levels were 1.7 to 2.2 mmol/L
      lower in the variable-dose insulin regimen group than in the other two treatment
      groups. No significant differences were found in the final prevalence or the
      cumulative incidence of total deaths, cardiovascular disease deaths, or
      myocardial infarctions among the three treatment groups, even when outcomes were
      adjusted for pertinent baseline cardiovascular risk factors. There was a slight
      suggestion only from post hoc analysis that patients in both insulin treatment
      groups, who were defined as having good glucose control, had fewer cardiovascular
      events than those with fair or poor control. The DCCT compared intensive insulin
      treatment with conventional insulin treatment (the mean hemoglobin A1c [HbA1c]
      level was 7.2% and 9.0%, respectively) in over 1400 patients with insulin
      dependent diabetes (IDDM) followed for up to 10 years (1983 to 1993). Three major
      cardiovascular events occurred in the intensive treatment group as compared with
      14 in the conventional treatment group (P > 0.05), and low-density lipoprotein
      cholesterol and triglyceride levels were substantially lower in the intensive
      treatment group. However, body mass index increased substantially more with
      intensive than with conventional therapy. CONCLUSIONS: The UGDP trial was flawed
      by inadequate power, insufficient separation of glycemic levels, and ignorance of
      smoking history as a possible confounder. In the DCCT, the number of
      cardiovascular events was few because the patients were young and had a
      relatively short duration of diabetes at baseline. In addition, total daily
      insulin doses were similar in the two DCCT treatment groups. For these reasons,
      neither trial provides a definitive answer to the question about the effects of
      intensive insulin therapy. A better designed clinical trial is needed to
      determine whether insulin treatment has beneficial or adverse effects, or even
      offsetting beneficial and adverse effects, on the risk for cardiovascular disease
      in NIDDM and IDDM.

PMID- 8554201
TI  - Do non-insulin-dependent diabetes mellitus and cardiovascular disease share
      common antecedents?
AB  - Recent evidence suggests that non-insulin-dependent diabetes mellitus (NIDDM) and
      cardiovascular disease, rather than being related as underlying disease and
      complication, share common genetic and environmental antecedents, that is, they
      "spring from the same soil." Fetal and early-life nutritional deficiencies appear
      to predispose persons to both NIDDM and cardiovascular disease in later life. The
      insulin resistance syndrome, including abdominal obesity, may constitute the
      intermediate link between fetal and early-life nutritional deficiency and later
      disease. The insulin resistance syndrome includes insulin resistance,
      hyperinsulinemia, abdominal obesity, dyslipidemia with high triglyceride and low
      high-density lipoprotein cholesterol levels, and hypertension. Each element of
      the insulin resistance syndrome has been firmly established as a risk factor for
      development of diabetes. In addition, most of these elements are also well
      recognized cardiovascular risk factors, although the weight of evidence now
      suggests that hyperinsulinemia itself is not. This last point is significant
      because of concern that aggressive insulinization of diabetic patients, which has
      been proved to reduce microvascular complications, might paradoxically increase
      the risk for large-vessel atherosclerosis. Available clinical trials suggest that
      this fear is unwarranted, but definitive trials are needed to resolve this
      important clinical question.

PMID- 8554202
TI  - Medical care for patients with diabetes. Epidemiologic aspects.
AB  - OBJECTIVE: To describe the epidemiologic characteristics of physician care and
      self-care for adults with diabetes in the U.S. population. DESIGN AND SUBJECTS:
      Data are drawn from the 1989 National Health Interview Survey, in which a
      personal household interview was administered to a representative sample of U.S.
      adults aged 18 years or older. The response rate was 96% (n = 84,572). All
      subjects identified as having diabetes previously diagnosed by a physician were
      asked a series of questions about their diabetes. Response rate for this
      representative sample of U.S. diabetic patients was 95% (n = 2405). MEASUREMENTS:
      Self-reported information was obtained about various aspects of diabetes care,
      including care by physicians and self-case practices of the diabetic persons.
      Sociodemographic and clinical factors that may influence diabetes care were also
      determined. RESULTS: More than 90% of diabetic adults had one physician for the
      usual care of their diabetes, but 32% made fewer than four visits to this
      physician each year. Most physician visits by diabetic patients were not made to
      diabetes specialists, and the visit rate to other health care professionals such
      as ophthalmologists, podiatrists, and nutritionists was low. About half of
      insulin-treated diabetic subjects used multiple daily insulin injections; and 40%
      of patients with insulin-dependent diabetes mellitus, 26% of those with non
      insulin-dependent diabetes mellitus (NIDDM) who were taking insulin, and 5% of
      those with NIDDM who were not taking insulin monitored their blood glucose level
      daily. Diabetes patient education classes had been attended by 35% of diabetic
      adults. CONCLUSIONS: These and other data indicate that medical care for diabetic
      patients and their self-care practices may not be optimal for prevention of
      diabetes complications. The Diabetes Control and Complications Trial showed that
      achieving and maintaining near-normal glycemia, with a concomitant 50% to 70%
      reduction in diabetes complications, may require close monitoring and ongoing
      support from a health care team, ample financial resources, and advanced patient
      knowledge and motivation. Providing this level of diabetes management to all
      diabetic persons may require major changes in the health care system and in
      patient self-care practices.

PMID- 8554203
TI  - Cardiovascular complications of diabetes mellitus: what we know and what we need
      to know about their prevention.
AB  - Cardiovascular disease is a major causes of morbidity and mortality in patients
      with non-insulin-dependent diabetes mellitus (NIDDM). With an increase in the
      number of older diabetic persons, an increase in U.S. minority populations with
      high rates of diabetes, and the proven success of new methods to reduce
      microvascular complications, the importance of diabetic macrovascular
      complications will increase. The relative effectiveness of different treatments
      to reduce the incidence of diabetic cardiovascular complications is poorly
      understood. In addition to relative efficacy, issues related to patient burden
      and the economic cost of different treatments must be considered. Some of the
      information needed to improve therapy therapy will be available soon from ongoing
      clinical trials. Obtaining definitive answers to other questions, especially
      those related to the relative benefit of intensive glucose level control compared
      with control of other known cardiovascular disease risk factors, will require
      additional studies. Although several questions unique to diabetic patients remain
      unanswered, results of previous clinical trials done among largely nondiabetic
      participants can be used to develop interim recommendations for cardiovascular
      disease prevention. Until definitive guidelines for prevention are established,
      combining aggressive therapy for known cardiovascular disease risk factors with
      efforts to normalize the glucose level offers the best chance to reduce the
      higher risk for cardiovascular disease associated with NIDDM.

PMID- 8554204
TI  - Glycemic control and the risk for coronary heart disease in patients with non
      insulin-dependent diabetes mellitus. The Finnish studies.
AB  - PURPOSE: To review population-based studies that investigated the association and
      nature of association between glycemic control and the risk for coronary heart
      disease in patients with non-insulin-dependent diabetes mellitus (NIDDM). DATA
      SOURCES: Study 1 included 133 newly diagnosed patients with NIDDM from eastern
      Finland, who were 45 to 64 years of age at baseline. These patients were followed
      up to 10 years for cardiovascular mortality. Study 2 included 229 newly or
      previously diagnosed patients with NIDDM from eastern Finland, aged 65 to 74
      years at baseline. These patients were followed up to 3.5 years for coronary
      heart disease mortality and all coronary heart disease events (mortality or
      nonfatal myocardial infarction). STUDY SELECTION: Prospective, population-based
      studies that included indicators of glycemic control and the evaluation of
      coronary heart disease and cardiovascular risk. RESULTS: Study 1: 10-year
      cardiovascular mortality was significantly and linearly associated with glycemic
      control (fasting blood glucose and glycated hemoglobin A1 levels) independently
      of the mode of treatment. A high fasting blood glucose level significantly
      predicted cardiovascular mortality in multiple logistic regression analysis
      independently of other risk factors. Study 2: Glycated hemoglobin A1c was the
      most important single risk factor associated with coronary heart disease death or
      all coronary heart disease events. In multiple logistic regression analysis,
      glycated hemoglobin A1c was significantly associated with coronary heart disease
      death after adjustment for other cardiovascular risk factors. CONCLUSIONS: Two
      prospective, population-based studies from Finland give evidence for the linear
      association of glycemic control with the risk for coronary heart disease in
      middle-aged and elderly patients with NIDDM.

PMID- 8554205
TI  - The feasibility of intensive insulin management in non-insulin-dependent diabetes
      mellitus. Implications of the Veterans Affairs Cooperative Study on Glycemic
      Control and Complications in NIDDM.
AB  - OBJECTIVE: To review the results from the Veterans Affairs Cooperative Study on
      Glycemic Control and Complications in NIDDM (VACSDM) and to discuss the
      implications of the results from this feasibility trial. DESIGN: A randomized
      clinical trial comprising 153 men with non-insulin-dependent diabetes mellitus
      (NIDDM) who remained hyperglycemic on usual pharmacologic therapy. Patients were
      randomized into two groups receiving either standard or intensive insulin therapy
      and were followed for 27 months. SETTING: Five Veterans Affairs medical centers.
      PATIENTS: 153 men with NIDDM, aged 40 to 69 years, who had hemoglobin A1c (HbA1c)
      levels of greater than 6.55% while receiving sulfonylurea or insulin therapy.
      INTERVENTION: Standard insulin therapy was one or two insulin injections daily.
      Intensive insulin therapy was done using a stepwise approach: 1) evening
      intermediate or long-acting insulin; 2) addition of daytime glipizide; 3) insulin
      twice daily, with no glipizide; and 4) insulin three to four times daily, with no
      glipizide. MEASUREMENTS: Fasting blood glucose and HbA1c levels, retinopathy,
      lipid and urinary albumin levels, cardiovascular events, hypoglycemia, and body
      mass index. RESULTS: In the intensive group, the HbA1c level fell 2.07 percentage
      points; the mean HbA1c level was 7.3% from 6 months onward. The standard group
      experienced little change. These changes occurred without significant weight gain
      and with a very low rate of severe hypoglycemia. Sixteen patients (20.5%) in the
      standard group and 24 patients (32%) in the intensive group had cardiovascular
      events (P = 0.1). CONCLUSIONS: It is feasible to achieve excellent glycemic
      control in men with NIDDM in whom standard pharmacologic therapy has failed. The
      benefit/risk ratio of intensive insulin management in this patient group is not
      established and has been made the subject of a long-term prospective clinical
      trial.

PMID- 8554206
TI  - United Kingdom Prospective Diabetes Study 17: a 9-year update of a randomized,
      controlled trial on the effect of improved metabolic control on complications in
      non-insulin-dependent diabetes mellitus.
AB  - PURPOSE: To report the progress (after 9-year follow-up) of a study designed to
      determine whether improved glucose control in patients with newly diagnosed non
      insulin-dependent diabetes mellitus (NIDDM) is effective in reducing the
      incidence of clinical complications. DATA SOURCE: A multicenter, randomized,
      controlled trial of different therapies for NIDDM. After initial diet therapy,
      4209 asymptomatic patients who remained hyperglycemic (fasting plasma glucose
      levels, 6.0 to 15.0 mmol/L) were assigned to either a conventional therapy
      policy, primarily with diet alone, or to an intensive therapy policy, aiming for
      fasting plasma glucose levels of less than 6.0 mmol/L, with assignment to primary
      therapy with sulfonylurea or insulin (which increased insulin supply) or
      metformin (which enhanced insulin sensitivity). RESULTS: All three modes of
      pharmacologic therapy in the intensively treated group-sulfonylurea, insulin, and
      metformin-had similar efficacy in reducing the fasting plasma glucose and
      glycated hemoglobin levels. Over 9 years, patients assigned to intensive therapy
      with sulfonylurea or insulin had lower fasting plasma glucose levels (median, 7.3
      and 9.0 mmol/L, respectively) than patients assigned to conventional therapy.
      Regardless of the assigned therapy, however, the fasting plasma glucose and
      hemoglobin A1c levels increased, and maintaining near-normal glycemia was, in
      general, not feasible. Even insulin therapy did not achieve the therapeutic goal
      of near-normal glycemia because of the difficulty in treating marked
      hyperglycemia and the risk for hypoglycemic episodes. Nine years after the
      diagnosis of diabetes, 29% of the patients had had a diabetes-related clinical
      end point, 20% had had a macrovascular complication, and 9% had had a
      microvascular complication. CONCLUSIONS: A report will be published in 1998 after
      a median duration from randomization of 11 years (range, 6 to 20 years) with an
      81% power at a 1% level of significance of detecting whether the obtained
      improvement in glucose control causes a 15% decrease or increase in the incidence
      of major complications and whether any specific therapy is advantageous or
      disadvantageous.

PMID- 8554207
TI  - Barriers to care in non-insulin-dependent diabetes mellitus. The Michigan
      experience.
AB  - OBJECTIVE: To determine the barriers to optimal care at the community level for
      patients with non-insulin-dependent diabetes mellitus (NIDDM). DESIGN:
      Comprehensive evaluation of the clinical, psychosocial, and educational status of
      community-based patients with NIDDM, with subsequent review by local diabetes
      advisory councils of this status and the care those patients have received. The
      frequency with which patients visited their physician for diabetes management,
      received patient education, received diet counseling, and were examined by an
      ophthalmologist-four services universally recognized to be components of optimal
      diabetes care-was determined for all patients. SETTING: Eight Michigan
      communities, four large and four small. PATIENTS: From 1988 to 1994, 1056
      patients with NIDDM defined by stimulated C-peptide criteria) were studied.
      RESULTS: The frequency with which all patients with NIDDM visited their community
      primary care physician in 1994 was 3.7 times per year (4.6 times for patients
      taking insulin and 3.2 times for those not taking insulin). Thirty-three percent
      of all patients with NIDDM (48% of those taking insulin and 24% of those not
      taking insulin) had received all three other essential services, whereas 15% (6%
      taking insulin and 20% not taking insulin) had never received any of these
      services. Factors contributing to this level of care and barriers preventing more
      intensive management of community-based patients with NIDDM were identified by
      the diabetes advisory councils as they analyzed data from their own communities.
      The councils determined that the main barriers to optimal care of community-based
      patients with NIDDM are that 1) NIDDM is not considered or managed as a serious
      problem by most physicians and their patients; 2) the genetic basis for and
      refractory nature of obesity are not generally appreciated; and 3) as a complex,
      multisystemic chronic illness, diabetes fits poorly in a health care delivery
      system designed to deal with acute and episodic illnesses. CONCLUSION: Most
      community-based patients with NIDDM are not aggressively managed because of
      attitudinal, educational, and systemic factors that act as barriers to optimal
      health care delivery.

PMID- 8554208
TI  - Improving diabetes care in the primary health setting. The Indian Health Service
      experience.
AB  - PURPOSE: To identify key systems issues from the Indian Health Service (IHS)
      experience that must be addressed to improve metabolic control among patients
      with non-insulin-dependent diabetes mellitus (NIDDM) who were followed in primary
      care settings. DATA SOURCES: Records of diabetic patients seen in IHS facilities
      in specific geographic regions from 1987 to 1994. STUDY SELECTION: A
      representative sample of charts from each facility was reviewed yearly to measure
      key variables. The sampling frame was the number of diabetic patients currently
      active on the registry and the sample size calculated to measure a 10% change in
      selected practices at each facility. EXTRACTION: Regional diabetes coordinators
      reviewed charts or trained local providers to sample and extract data in a
      standard format. RESULTS: Regional data were examined to show trends in the
      performance of immunizations and foot examinations and in other variables such as
      hypertension and metabolic control. The percentage of diabetic patients who
      received a single dose of pneumococcal vaccine improved from 24% in 1987 to 1988
      to 57% in 1994 (P < 0.01 for trend) among diabetic patients in Minnesota,
      Wisconsin, and Michigan. Rates of yearly comprehensive foot examination increased
      from 36% to 58% (P < 0.01 for trend) over the same period. In Montana and
      Wyoming, the percentage of diabetic patients with uncontrolled hypertension
      (defined as the mean of three systolic blood pressure measurements of > or = 140
      mm Hg or diastolic pressure measurements > or = 90 mm Hg, or both, during the
      previous year) decreased from 36% in 1992 to 25% in 1993 after the regional
      diabetes coordinator emphasized hypertension control. In 1994, when less emphasis
      was placed on hypertension, 33% of the diabetic patients had uncontrolled
      hypertension. Estimates of metabolic control from records of diabetic patients in
      Washington, Oregon, and Idaho in 1994 showed that 29% of patients had excellent
      metabolic control (a hemoglobin A1c [HbA1c] level < or = 7.5% or mean blood
      glucose level < or = 9.2 mmol/L) within the past year; only 9% experienced poor
      control (a HbA1c level > 12% or mean blood glucose level > 18.9 mmol/L).
      CONCLUSIONS: The IHS experience shows that standard, ongoing monitoring of key
      variables allows facilities to improve diabetes care. Simple, reliable methods of
      defining metabolic control combined with a feedback system in the primary care
      setting are needed to improve metabolic control in patients with NIDDM.

PMID- 8554209
TI  - Health care for persons with non-insulin-dependent diabetes mellitus. The German
      experience.
AB  - A structured treatment and education program for patients with non-insulin
      dependent diabetes mellitus (NIDDM) who are not taking insulin was developed,
      evaluated, and implemented at the primary health care level throughout Germany.
      The program is based on the definition of individual and pragmatic therapeutic
      goals for each patient, primarily using nondrug treatment, which includes
      systematic glycosuria self-monitoring by the patients and four structured
      sessions of group education held in a general practitioner's office. After
      documentation of the program's efficacy in a randomized, controlled trial and
      several pilot projects, the program has been officially incorporated into the
      general German health care scheme and includes payment to practicing physicians
      for each patient treated. More than 12,500 primary health care physicians have
      participated in special 2-day postgraduate courses given by diabetologists; these
      courses are a precondition to participating in the program. As part of the
      primary health care scheme, the NIDDM program will be continuously monitored for
      quality control and efficiency. Currently, similar structured treatment and
      education programs targeted to primary health care physicians are being
      introduced for both insulin-treated NIDDM and arterial hypertension.

PMID- 8554210
TI  - Management of non-insulin-dependent diabetes mellitus. The United Kingdom
      experience.
AB  - Care of persons with non-insulin-dependent diabetes mellitus (NIDDM) in the
      United Kingdom resembles that in the United States. However, health care practice
      in Europe is being influenced by the Saint Vincent Declaration, the joint
      European World Health Organization-International Diabetes Federation initiative,
      which emphasizes prevention of diabetic complications. In recent years, the
      responsibility for care for NIDDM has shifted in the United Kingdom to general
      practice teams. The effect of this shift on the quality of care and the
      coordinating and educational role of local diabetes specialist teams is
      discussed, as is the importance of an individualized "menu" of care for each
      patient. This menu aims for optimum blood glucose level control as well as
      detection and correction of risk factors for diabetic complications. The
      pervasive and dangerous notion of NIDDM as a "mild" disease must be corrected.
      The importance of systematic auditing of process and outcomes in diabetes care is
      emphasized, as is the need for regular data acquisition, aggregation, and
      analysis to achieve continuous improvement in the quality of care. Although
      patient-health professional encounters are the core of good diabetes care, the
      need for larger-scale appraisal on a local, regional, and national basis is now
      apparent.

PMID- 8554211
TI  - Diabetes in a managed care system.
AB  - Health care expenditures account for over 14% of the gross domestic product in
      the United States. Managed care has evolved to control these costs. Because
      diabetes accounts for nearly 15% of health care expenditures, the strategies used
      by managed care organizations are expected to have a particular effect on
      diabetes. Managed care organizations have two primary goals: to control costs and
      to provide care of sufficient quality to attract and satisfy enrollees. Managed
      care organizations have designed strategies to meet these goals. Four primary
      managed care strategies and their effects on diabetes care are discussed: 1)
      payment incentives rewarding desired provider practice patterns; 2) designation
      of providers who possess desirable practice behaviors; 3) coverage policies that
      control the services paid for; and 4) traditional insurance strategies that
      determine who is eligible for insurance and what premiums are to be paid. The few
      direct studies of the effects of each strategy on the care of diabetic persons
      are discussed. The conclusion is that although managed care organizations have
      the potential to provide excellent care for diabetic persons, little evidence
      exists that they have improved either the quality or the cost-effectiveness of
      diabetes care. Recommendations to guide the development of cost-effective care
      for diabetic persons are presented.

PMID- 8554212
TI  - Cost-effectiveness of detecting and treating diabetic retinopathy.
AB  - OBJECTIVE: To determine, from the health insurer's perspective, the cost of
      preventing vision loss in patients with diabetes mellitus through ophthalmologic
      screening and treatment and to calculate the cost-effectiveness of these
      interventions as compared with that of other medical interventions. DESIGN:
      Computer modeling, incorporating data from population-based epidemiologic studies
      and multicenter clinical trials. Monte Carlo simulation was used, combined with
      sensitivity analysis and present value analysis of cost savings. RESULTS:
      Screening and treatment of eye disease in patients with diabetes mellitus costs
      $3190 per quality-adjusted life-year (QALY) saved. This average cost is a
      weighted average (based on prevalence disease) of the cost-effectiveness of
      detecting and treating diabetic eye disease in those with insulin-dependent
      diabetes mellitus ($1996 per QALY), those with non-insulin-dependent diabetes
      mellitus (NIDDM) who use insulin for glycemic control ($2933 per QALY), and those
      with NIDDM who do not use insulin for glycemic control ($3530 per QALY).
      CONCLUSIONS: Our analysis indicates that prevention programs aimed at improving
      eye care for diabetic persons not only result in substantial federal budgetary
      savings but are highly cost-effective health investments for society.
      Ophthalmologic screening for diabetic persons is more cost-effective than many
      routinely provided health interventions. Because diabetic eye disease is the
      leading cause of new cases of blindness among working-age Americans, these
      results support the widespread use of screening and treatment for diabetic eye
      disease.

PMID- 8554213
TI  - The promise of computerized feedback systems for diabetes care.
AB  - Feedback control is an important mechanism for reaching a targeted goal. Biologic
      examples range from achieving the appropriate blood pressure level to glycemia
      control. Computer-based feedback control systems have many potential applications
      in medicine. Closed-loop systems directly sense the state of the patient and then
      deliver an intervention without human action. Closed-loop systems have been used
      to control postoperative fluid infusion, reduce malignant hypertension to a
      reasonable range through nitroprusside infusions, and control continuous insulin
      infusions-in effect, an artificial pancreas. Sensory problems have limited the
      direct application of closed-loop systems to date; most current medical uses of
      computer-based feedback control are open loop, where a human is interposed
      between the suggested intervention and the delivered treatment. Because many
      variables important to the management of diabetes are objective, many
      opportunities exist for open-loop control in diabetes management. Open-loop
      systems have already been used to suggest insulin dosage adjustments and
      treatment for hypercholesterolemia and to remind physicians of various mellitus.
      However, existing applications have only scratched the surface. Many more facets
      of diabetes management could be standardized and assisted by open-loop control
      systems if the management rules could be more exactly specified, a task requiring
      substantial time commitments by diabetologists. Efforts to translate existing
      knowledge bases into precise guidelines will be helpful, but new primary studies
      and decision analyses are needed to define the optimal use of some interventions.

PMID- 8554214
TI  - Forum One: Current recommendations about intensification of metabolic control in
      non-insulin-dependent diabetes mellitus.
AB  - PURPOSE: To review issues about intensive management of non-insulin-dependent
      diabetes mellitus (NIDDM) and to formulate recommendations for goals and general
      approaches to implementation of intensive management. METHOD: A panel of clinical
      scientists and practitioners specializing in diabetes initially used a formal
      nominal process to identify the points of agreement on major issues. These points
      were further refined in a general conference discussion. CONCLUSIONS: 1) On the
      basis of data from intervention trials in IDDM that prove that intensive glycemic
      control reduces microvascular and neuropathic complications, coupled with
      epidemiologic and basic scientific data that support the strong likelihood of a
      similar benefit in NIDDM, the goal of treatment in NIDDM should be near-normal
      glycemia (glycohemoglobin level no higher than 1.0% above the upper normal
      limit); 2) glycemic targets should be adjusted individually according to clinical
      factors such as increased risk for hypoglycemia, advanced age, or reduced life
      expectancy from comorbid conditions; 3) some degree of comprehensive and
      repetitive instruction about diet and exercise and the use of blood glucose self
      monitoring for all patients is essential to achieve the chosen targets; 4)
      intensive management of hyperglycemia should be instituted early and should
      initially emphasize diet and exercise therapy; staged introduction of oral
      hypoglycemic agents and finally insulin regimens of increasing complexity are
      recommended as needed to achieve glycemic targets; 5) comprehensive care must
      also include aggressive attempts to reduce cardiovascular risk factors
      (particularly hypertension, smoking, dyslipidemia, and obesity) as well as
      prevention of nephropathy and neuropathy; 6) the complex interaction among
      treatment regimens for hyperglycemia, dyslipidemia, obesity, and hypertension
      ideally requires a team approach, using a physician, diabetes educator, nurse,
      dietitian, and other health professionals; health insurers should make these
      resources available to generalists who currently care for most diabetic patients.

PMID- 8554215
TI  - Forum Two: Unanswered research questions about metabolic control in non-insulin
      dependent diabetes mellitus.
AB  - The participants of Forum Two addressed the unanswered research questions about
      metabolic control and non-insulin-dependent diabetes mellitus (NIDDM). The most
      compelling issue was the effect of metabolic control on both the development and
      progression of macrovascular disease in patients with NIDDM. Associated questions
      that could be answered by a well-controlled clinical trial related to the goal of
      blood glucose control in NIDDM in the elderly and in persons with clinical
      vascular disease. The specific suggestion was a trial similar to the Veterans
      Affairs Cooperative Study on Glycemic Control and Complications in NIDDM. Another
      important research issue that was discussed was the benefit of treating other
      risk factors such as hypertension and hyperlipidemia in diabetic patients. Yet
      another area discussed was the study of health services delivery to examine the
      best care-delivery methods for diabetes and other chronic diseases. Other areas
      of discussion centered on basic research, that is, the fundamental cause of
      insulin resistance and the genetics of NIDDM and the loss of protection against
      atherosclerosis in postmenopausal women with diabetes.

PMID- 8554216
TI  - Forum Three: Changes in the U.S. health care system that would facilitate
      improved care for non-insulin-dependent diabetes mellitus.
AB  - At the conclusion of the conference detailed in this supplement, conference
      attendees participated in one of three fora to discuss an assigned topic and
      incorporate conference presentations into the discussion. Forum Three, the
      results of which are reported here, addressed the challenging question of what
      changes in the U.S. health care system would facilitate improved care for
      patients with non-insulin-dependent diabetes mellitus (NIDDM). Using the nominal
      group process-a discussion technique designed to obtain a rank-ordered list of
      responses to the challenge question from a group of informed persons-Forum Three
      made the following priority recommendations: 1) Establish universal access to the
      comprehensive preventive services necessary to optimally manage the estimated 16
      million Americans with NIDDM; 2) create a system of co-management between primary
      and specialty care services; and 3) modify the current health care system to
      include a program for increased patient and public awareness of the seriousness
      of NIDDM, special training for primary care residents and practicing physicians
      in this area, development of standards of care, creation of a central
      coordinating agency for all aspects of diabetes care, and development of outcome
      based goals for patients and providers.

PMID- 8554217
TI  - Where do we go from here?

PMID- 8554218
TI  - Risks and benefits of intensive management in non-insulin-dependent diabetes
      mellitus. The Fifth Regenstrief Conference.

PMID- 8554219
TI  - The pathophysiology of diabetic complications: how much does the glucose
      hypothesis explain?
AB  - OBJECTIVE: To examine the putative pathogenetic mechanisms of the long-term,
      specific complications of diabetes mellitus. DATA SOURCES: Literature review
      relevant to long-term diabetic complications and their pathogenesis. STUDY
      SELECTION: Studies of animal models of diabetes, epidemiologic investigations of
      diabetes and its long-term complications, and interventional studies examining
      intensive treatment of diabetes and its effect on the development and progression
      of complications. DATA SYNTHESIS: Diabetic retinopathy, nephropathy, and
      neuropathy occur in all clinical forms of diabetes mellitus, regardless of the
      cause of the diabetes. Hyperglycemia appears to be the major variable shared
      among these different clinical forms; and epidemiologic data, studies in animal
      models of diabetes, and the results of recent interventional studies such as the
      Diabetes Control and Complications Trial, all support an important and perhaps
      dominant role of hyperglycemia in the pathogenesis of complications. However, the
      diverse complications may not share the same pathogenesis. Different pathogenetic
      mechanisms may operate in different types of diabetic complications or at
      different stages of specific complications, or both. CONCLUSIONS: The level of
      chronic glycemia is the best established concomitant factor associated with
      diabetic complications. The mechanism by which hyperglycemia might cause
      complications remains unknown, and evidence for a uniform pathogenetic mechanism
      is far from established.

PMID- 8554220
TI  - Relation of glycemic control to diabetic microvascular complications in diabetes
      mellitus.
AB  - OBJECTIVE: To describe the relation between glycated hemoglobin and the incidence
      or progression, or both, of diabetic microvascular complications in persons with
      insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM).
      DESIGN: Population-based on cohort study. SETTING: An 11-county area in southern
      Wisconsin. PATIENTS: All persons with IDDM diagnosed before age 30 and taking
      insulin (n = 996) and a probability sample (based on duration of disease) of
      persons diagnosed with diabetes at age 30 or older who were either taking insulin
      (n = 674) or not taking insulin (n = 696) and who participated in a baseline
      examination from 1980 to 1982. Survivors of the cohort were re-examined again in
      1984 to 1986 and 1990 to 1992. MEASUREMENTS: The incidence and progression of
      diabetic retinopathy was determined by masked grading of stereoscopic color
      fundus photographs using the modified Early Treatment Diabetic Retinopathy Study
      severity scale. Gross proteinuria was determined using a dipstick. Ten-year
      incidence of renal dialysis or transplantation or loss of tactile sensation or of
      temperature sensitivity was based on self-reported history. RESULTS: The glycated
      hemoglobin level at baseline was strongly related to the incidence or
      progression, or both, of diabetic retinopathy, the incidence of gross
      proteinuria, and the incidence of loss of tactile sensation or temperature
      sensitivity in persons with either IDDM or NIDDM. CONCLUSIONS: These prospective
      epidemiologic data suggest that glycemic control is similarly related to the
      incidence and progression of diabetic microvascular complications in both IDDM
      and NIDDM. However, further evidence from clinical trials in persons with NIDDM
      is necessary to assess the risks and benefits of such treatment in preventing
      these complications.

PMID- 8554221
TI  - Glucose control and insulin resistance in non-insulin-dependent diabetes
      mellitus.
AB  - Chronic hyperglycemia is implicated in the pathogenesis of microvascular,
      neurologic, and macrovascular complications of diabetes. Recent studies prove
      that near-normal glycemic control in insulin-dependent diabetes mellitus (IDDM)
      reduces the risk for the development and progression of microvascular and
      neurologic complications. With the expectation of comparable benefits, similar
      glycemic goals have been advocated for the management of non-insulin-dependent
      diabetes mellitus (NIDDM). However, using intensified insulin therapy to achieve
      near-normal glycemia in NIDDM may be problematic because of basic differences in
      pathophysiology of the two types of diabetes. Insulin resistance is a major
      contributor to the development of hyperglycemia in NIDDM and may prevent
      attainment of normoglycemia in most patients who are using the conventional
      approaches of diet, exercise, and oral hypoglycemic therapy. Near-normal glycemia
      in patients with NIDDM can usually be achieved with exogenous insulin but often
      requires large doses to overcome the insulin resistance. Intensive insulin
      therapy normalizes glycemia by decreasing hepatic glucose output and improving
      peripheral glucose uptake and may also improve insulin resistance and insulin
      secretion by reducing hyperglycemic glucotoxicity. However, large doses of
      exogenous insulin are associated with hyperinsulinemia and weight gain, but these
      effects may be minimized by combining insulin with other forms of therapy, for
      example, oral antidiabetic agents. When intensive management is instituted, the
      dose of exogenous insulin should be kept as low as possible. To do this, therapy
      for NIDDM must be part of a multifaceted approach combining insulin therapy with
      other effective forms of treatment such as counseling on diet and exercise
      therapy and the use of oral antidiabetic agents.

PMID- 8554222
TI  - Recent age-related trends in the use of thrombolytic therapy in patients who have
      had acute myocardial infarction. National Registry of Myocardial Infarction.
AB  - OBJECTIVE: To examine recent trends in the use of thrombolytic therapy in elderly
      patients who have had acute myocardial infarction and to determine whether
      failure to meet time-to-hospital presentation and electrocardiographic criteria
      might explain age-related differences in the use of thrombolytic therapy. DESIGN:
      A national registry of patients who have had acute myocardial infarction.
      SETTING: 1249 U.S. hospitals. PATIENTS: 350,755 patients who had an acute
      myocardial infarction from 1 July 1990 to 30 September 1994. MEASUREMENTS: Trends
      in the proportions of patients who received thrombolytic therapy were examined
      according to age and sex. The association between age and treatment with a
      thrombolytic agent was determined by crude and multivariable-adjusted analyses.
      RESULTS: Use of a thrombolytic agent was inversely related to patient age: Almost
      51% of patients younger than age 55 years received a thrombolytic agent during
      hospitalization for acute myocardial infarction; this proportion decreased to
      43.6% for patients aged 55 to 64 years, 33.0% for those aged 65 to 74 years,
      19.0% for those aged 75 to 84 years, and 7.4% for those aged 85 years or older.
      However, relative increases in the use of thrombolytic therapy over time were
      greatest for patients in the oldest age groups. Between 1 July 1990 and 30 June
      1991, 16.0% of patients aged 75 to 84 years received a thrombolytic agent
      compared with 21.4% between 1 June 1993 and 30 September 1994 (a 33.8% relative
      increase in use). Among persons aged 85 years or older, the proportion of treated
      patients increased from 5.3% to 9.1% over this same period (a 71.7% relative
      increase in use). Increases in thrombolytic use were most prominent for older
      women. After adjustment for sex, diagnosis by initial electrocardiogram,
      electrocardiogram-based infarction description, time from symptom onset to
      hospital presentation, and period of the acute myocardial infarction, the odds of
      receiving a thrombolytic agent were significantly reduced for patients in the
      older age groups compared with the odds for patients younger than age 55 years
      (for patients aged 75 to 84 years, the adjusted odds ratio was 0.27 [95% CI, 0.26
      to 0.28]; for patients aged 85 years or older, the odds ratio was 0.09 [CI, 0.08
      to 0.10]). CONCLUSIONS: Although older patients who have had acute myocardial
      infarction less commonly receive a thrombolytic agent, use of thrombolytic
      therapy in this population is expanding. However, substantial differences across
      age groups persist in the likelihood of receiving treatment, even after
      adjustment for potentially confounding factors. Age-related differences in
      thrombolytic use may not be completely explained by the degree to which older
      patients do not meet conventional eligibility criteria for thrombolytic therapy.

PMID- 8554223
TI  - Aspirin for secondary prevention after acute myocardial infarction in the
      elderly: prescribed use and outcomes.
AB  - OBJECTIVES: To determine how often aspirin was prescribed as a discharge
      medication to eligible patients 65 years of age and older who were hospitalized
      with an acute myocardial infarction; to identify patient characteristics
      associated with the decision to use aspirin; and to evaluate the association
      between prescription of aspirin at discharge and 6-month survival. DESIGN:
      Observational study. SETTING: All 352 nongovernment, acute care hospitals in
      Alabama, Connecticut, Iowa, and Wisconsin. PATIENTS: 5490 consecutive Medicare
      beneficiaries who survived an acute myocardial infarction, were hospitalized
      between June 1992 and February 1993, and did not have a contraindication to
      aspirin. MEASUREMENTS: Medical charts were reviewed to obtain information on the
      prescription of aspirin at discharge, contraindications, patient demographic
      characteristics, and clinical factors. RESULTS: 4149 patients (76%) were
      prescribed aspirin at hospital discharge. In a multivariable analysis, an
      increased prescribed use of aspirin at discharge was correlated with several
      indicators of better overall health status (better left ventricular ejection
      fraction, absence of diabetes, shorter length of hospital stay, higher albumin
      level, and discharge to the patient's home). The prescribed use of aspirin at
      discharge was also associated with several specific patterns of care, including
      the use of cardiac procedures, beta-blocker therapy at discharge, and aspirin
      during the hospitalization. The prescribed use of aspirin at discharge was
      associated with a lower mortality rate 6 months after discharge compared with no
      prescribed aspirin (odds ratio, 0.77; 95% CI, 0.61 to 0.98), even after
      adjustment for baseline differences in demographic, clinical, and treatment
      characteristics between the two groups. CONCLUSIONS: Aspirin was not prescribed
      at discharge to 24% of elderly patients who were hospitalized with an acute
      myocardial infarction and did not have a contraindication to aspirin. Several
      patient characteristics were associated with a higher risk for not being
      prescribed aspirin. Increasing the prescription of aspirin for these patients may
      provide an excellent opportunity to improve their care.

PMID- 8554224
TI  - Impaired antibody responses to pneumococcal polysaccharide in elderly patients
      with low serum vitamin B12 levels.
AB  - OBJECTIVE: To determine whether immunocompetent elderly patients with low serum
      vitamin B12 levels have impaired serum antibody responses to the 23-polyvalent
      pneumococcal polysaccharide vaccine. DESIGN: Controlled, prospective cohort
      study. MEASUREMENTS: 15 patients with low serum vitamin B12 levels and 15 age-
      and diagnosis-matched patients with normal levels were vaccinated. Serum antibody
      titers to 12 pneumococcal serotypes were measured by radioimmunoassay before and
      4 weeks after vaccination. RESULTS: The difference between the geometric mean of
      the vaccine antibody titers before and after vaccination for all 12 serotypes was
      lower (P = 0.005) in the patients with low vitamin B12 levels than in the
      patients with normal levels. When mean corpuscular volume and age were controlled
      for, vitamin B12 remained an independent predictor of antibody response (P =
      0.005). Erythrocyte mean corpuscular volume was also an independent predictor of
      the increase in titer (P = 0.03). CONCLUSIONS: Patients with low vitamin B12
      levels had impaired antibody responses to pneumococcal vaccine. Further study is
      necessary to determine whether treatment with vitamin B12 can enhance specific
      immunoglobulin synthesis and improve the clinical efficacy of the pneumococcal
      vaccine in patients with low vitamin B12 levels.

PMID- 8554225
TI  - Is it ever safe to stop azole therapy for Coccidioides immitis meningitis?
AB  - OBJECTIVE: To determine 1) whether patients with coccidioidal meningitis who had
      achieved remission with oral azole therapy were cured and 2) when oral azole
      therapy could be discontinued in these patients. DESIGN: Data were gathered on
      patients with coccidioidal meningitis who had successfully responded to azole
      therapy in previous clinical trials. SETTING: Referral centers, including
      university, county, and veterans' hospitals and clinics. PATIENTS: 18 patients in
      whom azole therapy for meningitis had been discontinued, usually because of a
      presumption of cure. MAIN OUTCOME MEASURES: Clinical and cerebrospinal fluid
      relapse. RESULTS: 14 of 18 patients (78% [95% CI, 52% to 94%]) had relapse with
      disseminated disease after discontinuation of therapy, for a total of 1
      nonmeningeal and 15 meningeal relapses to date. Relapse occurred both soon and
      late (range, 0.5 to 30 months) after therapy was discontinued. The
      characteristics of patients who did not have relapse, including the particular
      azole used, the duration of therapy, the reason therapy was discontinued, and the
      cerebrospinal fluid indices before discontinuation, were similar to the
      characteristics of patients who had relapse. Relapse had serious consequences in
      some patients; 3 patients died. CONCLUSION: Our data suggest 1) that disease is
      only suppressed in patients with meningitis who achieve remission while receiving
      azole therapy and 2) that discontinuing azole therapy is unsafe. The alternative
      is lifelong treatment with azoles; this appears to be acceptable, because
      toxicity is uncommon with triazole therapy, even long-term triazole therapy.

PMID- 8554226
TI  - HLA-identical sibling bone marrow transplantation in younger patients with
      chronic lymphocytic leukemia. European Group for Blood and Marrow Transplantation
      and the International Bone Marrow Transplant Registry.
AB  - OBJECTIVE: To characterize in detail the outcomes of HLA-identical sibling bone
      marrow transplantation for chronic lymphocytic leukemia (CLL) in patients younger
      than 60 years of age. DESIGN: Retrospective cohort study. SETTING: 30 centers for
      bone marrow transplantation worldwide, which reported data on outcome of HLA
      identical sibling bone marrow transplantation for CLL to the European Group for
      Blood and Marrow Transplantation or the International Bone Marrow Transplant
      Registry between 1984 and 1992. PATIENTS: 54 patients diagnosed with CLL (median
      age, 41 years; range, 21 to 58 years). The median interval from diagnosis to
      transplantation was 37 months (range, 5 to 130 months). At the time of
      transplantation, 3 patients were at Rai stage 0; 10 were at stage 1; 10 were at
      stage 2; 7 were at stage 3; and 22 were at stage 4. INTERVENTION: Transplant
      regimens varied. Most patients received high-dose cyclophosphamide and total body
      irradiation, followed by infusion of bone marrow from an HLA-identical sibling.
      After transplantation, immune suppression with cyclosporine or methotrexate or
      both was generally used to prevent graft-versus-host disease. MEASUREMENTS: The
      primary outcome was survival. We also studied hematologic remission, defined as
      normalization of the leukocyte count, hemoglobin level, and platelet count, and
      absence of lymphadenopathy and splenomegaly. RESULTS: 38 patients (70%) achieved
      hematologic remission. Twenty-four (44%) remain alive a median of 27 months
      (range, 5 to 80 months) after transplantation. Three-year survival probability
      was 46% (95% CI, 32% to 60%). Three patients who received transplants at Rai
      stage 0 remain alive 21, 32, and 45 months after transplantation. Three-year
      survival probabilities were as follows: 68% (CI, 38% to 98%) in 10 patients who
      received transplants at Rai stage 1, 30% (CI, 2% to 58%) in 10 patients who
      received transplants at Rai stage 2, 57% (CI, 21% to 93%) in 7 patients who
      received transplants at Rai stage 3, and 34% (CI, 12% to 56%) in 22 patients who
      received transplants at Rai stage 4 CLL. Five patients (9%) died of progressive
      leukemia and 25 (46%) of treatment-related complications. CONCLUSIONS: Bone
      marrow transplants from HLA-identical siblings can result in hematologic
      remission and survival in persons with CLL, but it is uncertain how these results
      compare with those of conventional therapies.

PMID- 8554227
TI  - Hyperkalemia in hospitalized patients treated with trimethoprim-sulfamethoxazole.
AB  - OBJECTIVE: To determine the effect of standard-dose trimethoprim-sulfamethoxazole
      on serum potassium concentration in hospitalized patients. DESIGN: Prospective
      chart review. SETTING: Community-based teaching hospital. PATIENTS: 105 patients
      with various infections were hospitalized and treated. Eighty patients treated
      with standard-dose trimethoprim-sulfamethoxazole (trimethoprim, < or = 320 mg/d;
      sulfamethoxazole, < or = 1600 mg/d) composed the treatment group; 25 patients
      treated with other antibiotic agents served as the control group. MEASUREMENTS:
      Serum sodium, potassium, and chloride concentrations; serum carbon dioxide
      content; anion gap; blood urea nitrogen level; and serum creatinine level.
      RESULTS: The serum potassium concentration in the treatment group (mean +/- SD)
      was 3.89 +/- 0.46 mmol/L (95% CI, 3.79 to 3.99 mmol/L), and it increased by 1.21
      mmol/L (CI, 1.09 to 1.32 mmol/L) 4.6 +/- 2.2 days after trimethoprim
      sulfamethoxazole therapy was initiated. Blood urea nitrogen levels increased from
      7.92 +/- 5.7 mmol/L (CI, 6.67 to 9.16 mmol/L) to 9.2 +/- 5.8 mmol/L (CI, 7.9 to
      10.5 mmol/L), and serum creatinine levels increased from 102.5 +/- 49.5 mumol/L
      (CI, 91.4 to 113.6 mumol/L) to 126.1 +/- 70.7 mumol/L (CI, 110.3 to 141.9
      mumol/L). Patients with a serum creatinine level of 106 mumol/L (1.2 mg/dL) or
      more developed a higher peak potassium concentration (5.37 +/- 0.59 mmol/L [CI,
      5.15 to 5.59 mmol/L]) than patients with a serum creatinine level of less than
      106 mumol/L (4.95 +/- 0.48 mmol/L [CI, 4.80 to 5.08 mmol/L]). Patients with
      diabetes had a slightly higher peak potassium concentration (5.14 +/- 0.45 mmol/L
      [CI, 4.93 to 5.39 mmol/L]) than did patients without diabetes (5.08 +/- 0.59
      mmol/L [CI, 4.93 to 5.23 mmol/L]), but the difference was not statistically
      significant. The serum potassium concentration in the control group was 4.33 +/-
      0.45 mmol/L (CI, 4.15 to 4.51 mmol/L), and it decreased nonsignificantly over 5
      days of therapy. CONCLUSIONS: Standard-dose trimethoprim-sulfamethoxazole therapy
      used to treat various infections leads to an increase in serum potassium
      concentration. A peak serum potassium concentration greater than 5.0 mmol/L
      developed in 62.5% of patients; severe hyperkalemia (peak serum potassium
      concentration > or = 5.5 mmol/L) occurred in 21.2% of patients. Patients treated
      with standard-dose trimethoprim-sulfamethoxazole should be monitored closely for
      the development of hyperkalemia, especially if they have concurrent renal
      insufficiency (serum creatinine level > or = 106 mumol/L).

PMID- 8554228
TI  - Resident research in internal medicine training programs.
AB  - OBJECTIVE: To determine how well medical residency programs are prepared to meet
      the new Accreditation Council of Graduate Medical Education (ACGME) accreditation
      guidelines for resident scholarly activity. DESIGN: Cross-sectional study using a
      mailed survey. PARTICIPANTS: Program directors of all ACGME-accredited internal
      medicine residency programs. MEASUREMENTS: Program directors were asked to list
      the scholarly activities and products of their residents and their programs'
      minimal expectations for resident research; available academic, faculty,
      technical, and personnel support for resident research; perceived barriers to
      resident research; and the desired educational and skill outcomes of resident
      research. The responses of university-based training programs were compared with
      those of non-university-based programs. RESULTS: 271 program directors returned
      the survey, yielding a response rate of 65%. Ninety-seven percent of all programs
      have established scholarly guidelines consistent with accreditation requirements.
      Although only 37% of programs reported having an organized, comprehensive
      research curriculum, 70% taught skills important to research. Technical support
      and resources were generally available for resident research; the most frequently
      cited barrier to resident research was lack of resident time. University-based
      and non-university-based training programs differed in important ways. Generally,
      non-university-based programs had more research activity and structure, and they
      exceeded university-based programs in the number of oral and poster presentations
      given at local, state, and national professional meetings. CONCLUSIONS: Most
      programs have in place the basic elements conducive to resident research. Program
      directors have identified and teach educational outcomes and skills that are
      likely to have lifelong benefits for most of their graduates.

PMID- 8554229
TI  - Vancomycin-resistant Staphylococcus aureus: perspectives on measures needed for
      control.
AB  - Given the dramatic increase in the incidence of vancomycin resistance among the
      enterococci and experimental evidence for the transfer of vancomycin resistance
      from enterococci to Staphylococcus aureus, there is concern that strains of S.
      aureus will emerge that are resistant to vancomycin. The result would be a highly
      virulent pathogen for which effective antimicrobial therapy would not be
      available. To prevent the nosocomial transmission of such an organism, stringent
      infection control policies need to be developed and implemented. We offer
      proposals that are based on the limited data available on the transmission and
      control of S. aureus and that may be used as starting points for the development
      of formal guidelines for the isolation of colonized and infected patients and for
      microbiology laboratory precautions.

PMID- 8554230
TI  - Medical therapy for elderly patients who have had myocardial infarction: too
      little to the late in life?

PMID- 8554231
TI  - Subtle cobalamin deficiency.

PMID- 8554232
TI  - Research during internal medicine residency training: meeting the challenge of
      the Residency Review Committee.

PMID- 8554233
TI  - Prophylaxis for HIV-related infections: a work in progress.

PMID- 8554234
TI  - The breakthrough.

PMID- 8554235
TI  - USPHS/IDSA guidelines for the prevention of opportunistic infections in persons
      infected with human immunodeficiency virus: a summary.

PMID- 8554236
TI  - Lung dysfunction and chronic liver disease.

PMID- 8554237
TI  - Lung dysfunction and chronic liver disease.

PMID- 8554238
TI  - Duplex scanning of renal arteries for stenosis.

PMID- 8554239
TI  - Duplex scanning of renal arteries for stenosis.

PMID- 8554240
TI  - Zidovudine in patients with HIV infection.

PMID- 8554241
TI  - Zidovudine in patients with HIV infection.

PMID- 8554242
TI  - Bacteriuria and incontinence in nursing home residents.

PMID- 8554243
TI  - Public policy governing organ and tissue procurement.

PMID- 8554244
TI  - Public policy governing organ and tissue procurement.

PMID- 8554245
TI  - Internet medical resources.

PMID- 8554246
TI  - Effects of intensive diabetes therapy on neuropsychological function in adults in
      the Diabetes Control and Complications Trial.
AB  - OBJECTIVE: To examine the effect of intensive therapy on neuropsychological
      performance in patients who participated in the Diabetes Control and
      Complications Trial (DCCT). DESIGN: Multicenter, randomized, controlled clinical
      trial. SETTING: 29 DCCT clinical centers. PATIENTS: 1441 patients with insulin
      dependent diabetes mellitus (IDDM) between 13 and 39 years of age who had had
      IDDM for 1 to 15 years and had no or minimal retinopathy or nephropathy at
      baseline. Volunteers were excluded if they had a history of substance abuse,
      psychological disturbance, or recurrent hypoglycemia with coma or seizure.
      INTERVENTION: Intensive therapy with 3 or more daily insulin injections or
      continuous subcutaneous insulin infusion, guided by 4 or more glucose tests per
      day, compared with conventional therapy with 1 or 2 daily insulin injections.
      OUTCOME MEASURES: Neuropsychological assessments were done at baseline; years 2,
      5, and 7; and the end of the study. Eight cognitive domain scores were developed
      from the test results and were used to identify patients whose neuropsychological
      performance had clinically worsened. RESULTS: Intensive therapy did not affect
      neuropsychological performance. In addition, patients who had repeated episodes
      of hypoglycemia did not perform differently than patients who did not have
      repeated episodes. CONCLUSION: Intensive therapy and the attendant risk for
      hypoglycemia were not associated with neuropsychological impairment in the DCCT.

PMID- 8554247
TI  - Doxycycline compared with azithromycin for treating women with genital Chlamydia
      trachomatis infections: an incremental cost-effectiveness analysis.
AB  - OBJECTIVE: To compare the economic consequences of doxycycline therapy with those
      of azithromycin therapy for women with uncomplicated cervical chlamydial
      infections. DESIGN: Decision analysis in which the health outcomes, costs, and
      cost-effectiveness of two provider-administered treatment strategies for women
      with uncomplicated cervical chlamydial infections were compared: 1) initial
      therapy with doxycycline, 100 mg orally twice daily for 7 days (estimated cost,
      $5.51) and 2) initial therapy with azithromycin, 1 g orally administered as a
      single dose (estimated cost, $18.75). RESULTS: Under baseline assumptions, the
      azithromycin strategy incurred fewer major and minor complications and was less
      expensive overall than the doxycycline strategy despite a higher initial cost for
      acquiring antibiotic agents. In univariate sensitivity analyses, the azithromycin
      strategy prevented more major complications but was more expensive than the
      doxycycline strategy when doxycycline effectiveness was greater than 0.93. In a
      multivariate sensitivity analysis combining 11 parameter estimates selected so
      that the cost-effectiveness of the doxycycline strategy would be maximized
      relative to that of the azithromycin strategy, the azithromycin strategy resulted
      in fewer complications but was more costly. The incremental cost-effectiveness
      was $521 per additional major complication prevented. However, if the difference
      in the cost of azithromycin and doxycycline decreased to $9.80, the azithromycin
      strategy was less expensive and more effective, even under these extreme
      conditions. CONCLUSIONS: On the basis of the best available data as derived from
      the literature and experts, the azithromycin strategy was more cost-effective
      than the doxycycline strategy for women with uncomplicated cervical chlamydial
      infections. Despite the dominance of the azithromycin strategy over the
      doxycycline strategy, the adoption of the azithromycin strategy may be limited by
      the practical financial constraints of our currently fragmented health care
      system, in which the costs and benefits of preventing chlamydia sequelae are
      often incurred by different components of the system.

PMID- 8554248
TI  - Vitamin D supplementation and fracture incidence in elderly persons. A
      randomized, placebo-controlled clinical trial.
AB  - OBJECTIVE: To determine whether vitamin D supplementation decreases the incidence
      of hip fractures and other peripheral bone fractures. DESIGN: Prospective, double
      blind trial. SETTING: Community setting (Amsterdam and surrounding area).
      PATIENTS: 2578 persons (1916 women, 662 men) 70 years of age and older (mean age
      +/- SD, 80 +/- 6 years) living independently, in apartments for elderly persons,
      or in homes for elderly persons. INTERVENTION: Participants were randomly
      assigned to receive either vitamin D3, 400 IU in one tablet daily, or placebo for
      a maximum of 3.5 years. MEASUREMENTS: Dietary calcium intake and serum 25
      hydroxyvitamin D [25(OH)D] were estimated in a subset of participants. During
      follow-up, attention was concentrated on hip fractures and other peripheral
      fractures. The maximal follow-up period was 4 years. The results were evaluated
      by survival analysis. RESULTS: Mean dietary calcium intake from dairy products
      was 868 mg/d. Mean serum 25(OH)D concentration in the third year of the study was
      23 nmol/L in the placebo group and 60 nmol/L in the vitamin D group. Median
      follow-up was 3.5 years, and total follow-up was 8450 patient-years. During
      follow-up, 306 persons in the placebo group and 282 persons in the vitamin D
      group died (P = 0.20). Hip fractures occurred in 48 persons in the placebo group
      and 58 persons in the vitamin D group (P = 0.39, intention-to-treat analysis).
      Other peripheral fractures occurred in 74 persons in the placebo group and 77
      persons in the vitamin D group (P = 0.86). CONCLUSION: Our results do not show a
      decrease in the incidence of hip fractures and other peripheral fractures in
      Dutch elderly persons after vitamin D supplementation.

PMID- 8554249
TI  - Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993.
AB  - OBJECTIVE: To define the prognosis for and radiographic presentation of patients
      with pulmonary amyloidosis. DESIGN: Retrospective review of the Mayo Clinic
      experience with biopsy-proven pulmonary amyloidosis from 1980 to 1993. SETTING:
      Tertiary care center. PATIENTS: Patients with pulmonary biopsy specimens showing
      amyloid deposition. MEASUREMENTS: Medical records were reviewed, and pertinent
      information was recorded, including demographic data, type of pulmonary biopsy,
      results of biopsies of nonpulmonary sites and of immunoelectrophoresis, and other
      clinical, radiographic, and laboratory information necessary for distinguishing
      localized pulmonary amyloidosis, primary systemic amyloidosis, secondary
      amyloidosis, and familial amyloidosis. RESULTS: 35 of 55 patients with pulmonary
      amyloidosis had primary systemic amyloidosis that presented radiographically as
      an interstitial or reticulonodular pattern with or without pleural effusion. The
      median survival after diagnosis was 16 months. Nodular pulmonary "amyloidomas"
      (nodular amyloid lesions) were not associated with systemic disease and were
      associated with a benign prognosis. Three of 4 patients with localized
      tracheobronchial amyloidosis required Nd:YAG (neodymium:yttrium-aluminum-garnet)
      laser therapy for obstructive symptoms. "Senile" amyloid deposition was an
      incidental finding in some patients at autopsy. CONCLUSIONS: Localized
      amyloidomas are characterized by a benign course and are not associated with
      systemic amyloidosis. Despite its localized nature, tracheobronchial amyloid
      deposition may be asymptomatic or may result in significant morbidity due to
      obstructive phenomena. Pulmonary amyloidosis associated with primary systemic
      amyloidosis generally presents as a diffuse interstitial pattern with or without
      pleural effusion. Complete survival data indicate that long-term outcome is poor
      after diagnosis. We describe the largest series of patients diagnosed by
      bronchoscopic lung biopsy. Despite reports to the contrary, we have found
      bronchoscopic lung biopsy to be a safe and effective diagnostic technique.

PMID- 8554250
TI  - Differences in generalists' and cardiologists' perceptions of cardiovascular risk
      and the outcomes of preventive therapy in cardiovascular disease.
AB  - OBJECTIVE: To compare generalists' and cardiologists' estimates of baseline
      cardiovascular risk and the outcomes of preventive therapy. DESIGN: Cross
      sectional mail survey using written case simulations of typical patients from
      primary prevention trials for hypercholesterolemia and isolated systolic
      hypertension, and tertiary prevention studies of coronary artery bypass surgery
      for chronic stable angina with left main coronary stenosis. PARTICIPANTS:
      Nationally representative sample of 599 practicing family physicians, general
      internists, and cardiologists selected from the American Medical Association
      masterfile. Among eligible physicians, 84 (44%) of 191 family physicians, 77
      (40%) of 194 general internists, and 66 (34%) of 194 cardiologists responded.
      MEASUREMENTS: Estimates of risk at baseline and after therapy, and whether
      therapy generally would be recommended. RESULTS: For both primary prevention case
      simulations (scenarios), cardiologists provided lower, more accurate estimates of
      baseline cardiovascular risk and of absolute therapeutic benefit than either
      family physicians or general internists. The range of the generalists' estimates
      was extremely wide. Perceptions of relative risk reduction and treatment
      recommendations for the primary prevention scenarios did not differ among
      specialties. Overall, generalists who would not recommend primary preventive
      therapy in these scenarios appeared to give more accurate estimates than did
      generalists who would recommend such therapy. CONCLUSIONS: Many generalists have
      inflated perceptions of cardiovascular risk without treatment and of the benefit
      of risk-modifying medical treatment. Further study should assess the reasons for
      these misperceptions and their effect on counseling about primary preventive
      therapy.

PMID- 8554251
TI  - The relation of passage of gas an abdominal bloating to colonic gas production.
AB  - OBJECTIVE: To determine the relation of gas passage and abdominal bloating to the
      production of gas in the colon. DESIGN: Randomized, double-blind, crossover study
      of gaseous symptoms during a 1-week period. SETTING: A Veterans Affairs medical
      center. PARTICIPANTS: 25 healthy medical center employees. INTERVENTION:
      Participants' diets were supplemented with either a placebo (10 g of lactulose, a
      nonabsorbable sugar), psyllium (a fermentable fiber), or methylcellulose (a
      nonfermentable fiber). MEASUREMENTS: All participants were polled for gaseous
      symptoms (including number of gas passages, impression of increased rectal gas,
      and abdominal bloating), and five were examined for breath hydrogen excretion.
      RESULTS: Participants passed gas 10 +/- 5.0 times per day (mean +/- SD) during
      the placebo period. A significant increase in gas passages (to 19 +/- 12 times
      per day) and a subjective impression of increased rectal gas were reported with
      lactulose but not with either of the two fiber preparations. Breath hydrogen
      excretion, an indicator of hydrogen production in the colon, did not increase
      after ingestion of either of the fibers. However, a statistically significant (P
      < 0.05) increase in feelings of abdominal bloating (which the participants
      perceived as excessive gas in the bowel) was reported with both fiber
      preparations and with lactulose. CONCLUSIONS: The physician should distinguish
      between excessive gas (which indicates excessive gas production) and feelings of
      bloating (which are usually unrelated to excessive gas production). Treatment of
      the former consists of limiting the supply of fermentable material to the colonic
      bacteria. Symptoms of bloating usually indicate the irritable bowel syndrome, and
      therapy should be directed accordingly.

PMID- 8554252
TI  - Hyperlipidemia and pancreatitis during pregnancy in two sisters with a mutation
      in the lipoprotein lipase gene.
AB  - OBJECTIVE: To explore genetic mechanisms for pregnancy-associated pancreatitis
      and hyperlipidemia in two sisters. DESIGN: Case history. SETTING: Tertiary care
      facility with outpatient follow-up. PATIENTS: Two sisters with acute pancreatitis
      and the acute respiratory distress syndrome were admitted (patient 1) or
      transferred (patient 2) to an intensive care setting with severely elevated
      triglyceride levels. Patient 1 was in the last trimester of pregnancy; patient 2
      was 1 month postpartum. Both patients were of French Canadian ancestry.
      INTERVENTION: Acute treatment was directed at stabilizing both patients medically
      (with fat restriction) and one patient surgically (patient 2). Treatment with fat
      restriction, weight loss, and gemfibrozil was continued after hospitalization.
      RESULTS: Through DNA sequencing, we detected a mutation at amino acid residue 188
      of lipoprotein lipase (LPL), reflecting product from one allele of the LPL gene
      in which a glutamine residue was substituted for a glycine (gly 188-->glu).
      CONCLUSION: LPL plays a key role in regulating triglyceride levels in pregnancy.
      Mutations of LPL may place the patient at risk for pancreatitis. This
      heterozygous LPL mutation, gly 188-->glu, is prevalent in certain ethnic groups
      and may be a common cause of pancreatitis associated with pregnancy.

PMID- 8554253
TI  - Understanding intestinal spore-forming protozoa: cryptosporidia, microsporidia,
      isospora, and cyclospora.
AB  - OBJECTIVES: To summarize recent information about the "new" gastrointestinal
      protozoal pathogens (cryptosporidia, microsporidia, isospora, and cyclospora) and
      to help practicing clinicians integrate this information into their clinical
      databases by emphasizing the similarities among these organisms. DATA SOURCES:
      Relevant English-language articles published between 1988 and 1995 were
      identified through a MEDLINE search done using the names of the intestinal spore
      forming protozoa. Articles cited in the bibliographies of these and other
      articles were searched manually. STUDY SELECTION: Studies that contained
      information on the history, taxonomy, life cycle, epidemiology, pathogenesis,
      clinical manifestations, diagnosis, and treatment of the pathogens were reviewed.
      DATA EXTRACTION: Cryptosporidium parvum, Isospora belli, Cyclospora cayetanensis,
      Enterocytozoon bieneusi, and Septata intestinalis are intestinal spore-forming
      protozoa that cause intracellular infections, predominantly in the epithelial
      cells of the intestine. They are transmitted either by stool from person to
      person or through contaminated water or food by an infectious particle called a
      spore or oocyst. Asymptomatic infections occur; the most common symptom of
      infection is diarrhea. Infections have been associated with intestinal
      inflammation, disordered architecture (such as villus blunting), and abnormal
      function (for example, malabsorption). Mild to moderate, self-limited diarrhea is
      common in healthy persons, but patients with immune dysfunction can have severe
      intestinal injury and prolonged diarrhea. Diagnosis is made by a microscopic
      examination of the stool and the use of appropriate staining techniques.
      Effective antibiotic treatment for prolonged infection in immunocompromised
      patients is available for most of these infections. CONCLUSIONS: The intestinal
      spore-forming protozoa are four frequently identified gastrointestinal pathogens
      that have important similarities in epidemiology, disease pathogenesis, clinical
      manifestations, diagnosis, and treatment.

PMID- 8554254
TI  - Integrated health care, capitated payment, and quality: the role of regulation.
AB  - Concerns about the effect of managed care techniques on the quality of medical
      care have been raised in many quarters. Physicians have advocated the reiteration
      of professional ethics or even the prohibition of market incentives in health
      care as solutions to the problem of cost-quality tradeoffs in managed care
      systems. However, few recognize the existing systems for the regulation of
      managed care or consider how additional regulation could alleviate some of the
      potential problems posed by market-based competition. We review the evolution and
      growth of managed care organizations and the payment techniques that could cause
      a conflict between patient welfare and physician income. We then discuss the
      existing types of federal and state regulation of managed care and suggest some
      new incentives that could buttress the ethical practice of medicine in the
      medical marketplace.

PMID- 8554255
TI  - Capitated payment for medical care and the role of the physician.

PMID- 8554256
TI  - Empiric outpatient management of HIV-related pneumonia: economical or unwise?

PMID- 8554257
TI  - Nitric oxide and hemodialysis-induced hypotension.

PMID- 8554258
TI  - The challenge of postal medicine.

PMID- 8554259
TI  - Metronidazole in treating portosystemic encephalopathy.

PMID- 8554260
TI  - Tuberculosis: yesterday, today, and tomorrow.

PMID- 8554261
TI  - Misrepresentation of academic accomplishments by applicants for gastroenterology
      fellowships.

PMID- 8554262
TI  - Misrepresentation of academic accomplishments by applicants for gastroenterology
      fellowships.

PMID- 8554263
TI  - Misrepresentation of academic accomplishments by applicants for gastroenterology
      fellowships.

PMID- 8554264
TI  - Misrepresentation of academic accomplishments by applicants for gastroenterology
      fellowships.

PMID- 8554265
TI  - Misrepresentation of academic accomplishments by applicants for gastroenterology
      fellowships.

PMID- 8554266
TI  - [Immediate intraperitoneal chemotherapy after surgery for the reduction of
      peritoneal malignancies: for what purpose and for whom?].
AB  - Immediate intraperitoneal chemotherapy after reduction surgery in peritoneal
      carcinomatosis. Why and in which patients?

PMID- 8554267
TI  - [Imaging of cancer of the esophagus: ultrasound-endoscopy or computed
      tomography?].
AB  - The aim of this retrospective study, in 100 patients who had an esophagectomy
      from 1987 to 1992 for squamous cell carcinoma of the thoracic esophagus, was to
      determine the accuracy of endoscopic ultrasonography (EUS) and computed
      tomography (CT) in the preoperative staging of esophageal squamous cell carcinoma
      (SCC). The EUS report were compared to the pathological findings for the T stage.
      Both EUS and CT reports were compared with surgical and pathological findings for
      N stage (N0/N1) and mediastinal extension. In the 100 patients, EUS accuracy for
      T stage was 80%; EUS was more accurate for N stage than CT (71% vs 55%
      respectively; p < 0.02), and as accurate as CT for mediastinal extension (86% vs
      85%). In the 26 SCC estimated superficial by EUS (all passed through), EUS
      accuracy was 92% for T stage and 77% for the distinction between mucosal and
      submucosal tumours; for N stage, EUS and CT accuracies were equivalent (77% vs
      81%). In the 44 SCC passed and estimated advanced by EUS, EUS accuracy for T
      stage was 68%; EUS was more accurate than CT for N stage (77% vs 48%, p < 0.01)
      and as accurate as CT for mediastinal extension (86 vs 84%). In the 30 SCC not
      passed by EUS, accuracies of EUS and CT were equivalent for N stage (57% vs 47%)
      and for mediastinal extension (73% vs 73%). This study suggests that: a) for SCC
      estimated superficial by EUS, EUS does not differentiate reliably mucosal from
      submucosal tumors and CT is useless; b) routine EUS seems unnecessary for SCC not
      passed through by endoscopy; c) CT is still useful in patients with advanced SCC,
      mainly for detection of distant metastases.

PMID- 8554268
TI  - [Intrahepatic portasystemic shunt and hemorrhagic emergencies in the cirrhotic
      patient].
AB  - From March 1992 to March 1994, 26 patients underwent Transjugular Intrahepatic
      Portosystemic Shunt (TIPS) for emergency treatment of variceal bleeding. Patients
      were all cirrhotic, with a mean age 55 +/- 13 yrs, Child's score was A = 4, B =
      10, C = 12. TIPS was performed in case of failure or impossibility to obtain
      hemostasis after endoscopic and/or medical treatment. Hemostasis was successful
      in all cases of TIPS, and the portocaval gradient was lowered from 19 to 9 mmHg.
      Early complications occurred in 30% of cases. They consisted of: spontaneously
      regressive hemobilia (15%) and shunt thrombosis (15%) (3/4 were repermeabilized).
      Early mortality accounted for 15% of patients in the whole group and 25% in Child
      C'patients. During follow-up (m = 8 +/- 6 m), only one patient rebled, de novo
      hepatic encephalopathy occurred in 15% of patients always regressive in response
      to Lactulose therapy. One year mortality rate was 57%. A comparison between TIPS
      and other emergency hemostasis methods: endoscopic sclerotherapy, surgical
      portocaval shunt and esophageal transsection was performed on the early mortality
      rate according to the percentage of Child C'patients in the various series. TIPS
      is better than other methods in series with a low percentage of Child C'patients.
      TIPS should be proposed: in case of failure of endoscopic methods; for patients
      waiting for liver transplantation; when portal vein patency is compromised by
      thrombosis. This last indication implies that portal patency must be confirmed
      with angiography or better by with duplex sonography once primary hemostasis of
      variceal bleeding has been completed.

PMID- 8554269
TI  - [Value of selective clamping in major hepatectomies].
AB  - Charts of 100 consecutive patients who had undergone liver resection, performed
      by a single surgeon, during the 10 year period from 1983 to 1993 were reviewed.
      Liver trauma was excluded. The age of the patients ranged from 14 to 78 years,
      with a mean age of 52 +/- 12.3. Indications for liver resection were malignant
      tumors in 73 patients and benign disease in another 27 patients. The remnant
      liver was pathologic in 24 cases (21 cirrhosis, 3 chronic hepatitis). The extent
      of liver resection was major (> 3 segments) in 51 cases, and minor in 45 cases.
      Postoperative complications, including death, occurred in 24% of cases. Five
      complications required reoperation. Hospital mortality was 4%. Multivariate
      analysis demonstrated two major risk factors of morbidity: intraoperative blood
      transfusion, and cirrhosis. Age of patients was the only risk factor of
      mortality. In major resection, four categories of patients were established
      according to the type of hepatic inflow occlusion. Each group was comparable.
      Selective vascular clamping (selective control of the hilar vessels to the liver
      and selective hepatic vein occlusion) decreased the morbidity and post operative
      liver failure rate (p < 0.05). On the other hand, no correlation was observed
      between the type of hepatic inflow occlusion and the hospital mortality.

PMID- 8554270
TI  - [Laparoscopic treatment of common bile duct calculi].
AB  - Laparoscopic exploration of the common bile duct is now technically possible.
      This prospective study evaluates the feasibility of the different techniques and
      their complications. From January 1990 to March 1995, 140 patients, aged from 22
      to 92, underwent laparoscopic treatment for choledocholithiasis. A transcystic
      approach was attempted in 70 patients and was successful in 46 (65.7%). The
      failures were treated by 19 laparoscopic choledochotomies and 5 postoperative
      endoscopic sphincterotomies. A choledochotomy was performed in 89 cases and was
      successful in 85 (94.4%). The failures were treated by 3 laparotomies and 2
      postoperative endoscopic sphincterotomy. The total success rate was 92.8%
      (130/140). The 5 local complications were pain (1), liver injury (1), and wound
      abscess (2), bleeding from a trocar site. Heart failure (medical treatment) (2),
      gastrointestinal haemorrhage from intestinal angiomas, severe pancreatitis after
      transcystic failure and psychiatric disorders were the 5 general complications.
      The total morbidity rate was 7.1%. There were 2 residual common bile duct stones.
      The mortality rate was 0. Mean hospital stay was 7.8 days. Laparoscopic
      exploration of the common bile duct appears to be safe and effective and should
      be included in the management protocol of choledocholithiasis.

PMID- 8554271
TI  - [Value of celioscopy in the diagnosis of abdominal wounds].
AB  - Gunshot or stab wounds with equivocal evidence of intraabdominal injury lead to
      negative laparotomy in 20% to 30% of cases. The aim of this prospective study was
      to evaluate, in hemodynamically stable patients, the role of laparoscopy in order
      to reduce the rate of unnecessary laparotomies for such wounds. This study was
      carried out in 21 patients. Laparoscopy revealed 15 penetrating wounds (71.4%)
      with two isolated diaphragmatic injuries. Eight laparotomies (38%) for visceral
      injuries were performed on the 15 penetrating wounds. The laparoscopic
      exploration was complete in 7 cases without laparotomy. Thirteen unnecessary
      laparotomies were avoided (62%). Laparoscopy was found to have a 100% specificity
      and sensitivity for the diagnosis of peritoneal effraction and diaphragmatic
      injury. Laparoscopy is very effective for evaluation of equivocal penetrating
      wounds.

PMID- 8554272
TI  - [Intestinal infarctions. A re-evaluation of prognostic factors of postoperative
      mortality].
AB  - The aim of this study, based on a series of 67 patients, was to assess the
      prognostic factors of postoperative mortality of intestinal infarctions (small
      and large bowel). Known risk factors were studied (age, sex, shock, Concomitant
      disease, use of arteriography and vasodilators), together with less studied
      factors, such as recent vascular or cardiac surgery less than 4 months before the
      infarction and length of bowel infarction. Postoperative mortality was defined as
      any death occurring within 45 days after surgery. The risk factors were assessed
      by univariate and multivariate analysis with logistic regression. The
      postoperative mortality was 63%. Age, shock, other medical diseases, recent
      cardiovascular surgery, and length of bowel infarction were significant
      predictive factors of postoperative mortality on univariate analysis. Shock, age
      greater than 70 years and recent cardiovascular surgery were three independent
      risk factors selected on multivariate analysis with equivalent weights.

PMID- 8554273
TI  - [Total hysterectomy for benign pathologies. Conventional celiosurgical
      technique].
AB  - The standard technique for total laparoscopic hysterectomy is characterised by
      two essential points. The first is that all instruments are reusable and the
      second is that hemostasis is ensured by bipolar coagulation. It is a safe
      technique with a cost comparable to that of vaginal or abdominal hysterectomies.
      The routine use of disposable material and automatic disposable staplers for
      laparoscopic hysterectomies is debatable, as the considerable increase in cost is
      not accompanied by benefit for the patient or the community. Although
      laparoscopic hysterectomy is a feasible technique, all hysterectomies should not
      be performed by this route. If the operation is feasible quickly and under good
      conditions via the vaginal route, laparoscopic surgery is not indicated.
      Laparoscopic surgery is only indicated when vaginal surgery is difficult and/or
      contra-indicated. The elective indications for total laparoscopic hysterectomy
      are severe adhesions, deep endometriosis and especially a limited vaginal
      accessibility associated with a narrow vagina and a fixed or non prolapsed
      uterus. While a average of three quarters of hysterectomies (excluding cases of
      uterogenital prolapse) are currently performed via a laparotomy, laparoscopic
      surgery can reduce this rate to approximately 10 to 20 per cent.

PMID- 8554274
TI  - [Pre- and retro-anal myorrhaphy in the treatment of severe anal incontinence.
      Clinical and manometric results].
AB  - Optimal surgical treatment for neuropathic severe anal incontinence is still
      controversial: the combination of pre-anal levator plication and post-anal repair
      (Parks) has been recently described. This non-randomized prospective study
      evaluated the results of pre- and post-anal repair for medically non-corrected
      neuropathic and traumatic anal incontinence. Ten female patients (mean age: 59)
      were operated by pre- and post-anal levatorplasty (total pelvic floor repair).
      Incontinence was scored clinically according to the Jorge and Wexner score
      (normal: 0, max.: 20) and with no rectal manometry, before and after surgery.
      Fourteen months after surgery (range: 9-18 months), anal continence for stools
      was achieved in 7 out of 10 patients: the patients clinical scores decreased from
      15 (12-19) pre-operatively to 6 (1-18) post-operatively (p < 0.01) (4 for good
      results, 17 for the 3 failures). No manometric parameter was able to predict or
      explain postoperative functional results. Only anal canal length and maximal
      amplitude of anal contractions were significantly improved from 3.0 cm (2.0-4.0)
      to 3.5 cm (2.2-4.5), p < 0.05) for the former and from 54 to 69 cm H2O for the
      latter (p < 0.05). In this small series, pre- and post-anal levatorplasty
      effectively corrected severe neuropathic anal incontinence in the short-term, in
      70% of cases. In our experience, this technique appears to be superior to post
      anal repair, without increasing technical problems or morbidity.

PMID- 8554275
TI  - [Surgical treatment of ulcero-hemorrhagic rectocolitis].
AB  - When surgical treatment is indicated in the course of ulcerative colitis, several
      operations may be performed. In the vast majority of patients, total
      proctocolectomy and ileal pouch-anal anastomosis is the procedure of choice.
      Other operations (total proctocolectomy with Brooke ileostomy, total colectomy
      with ileorectal anastomosis or with Kock pouch) can also be used in certain
      circumstances. Postoperative quality of life must be considered before any
      decision is finalized.

PMID- 8554276
TI  - [Hepatobiliary radionuclide imaging. Clinical applications].
AB  - Iminodiacetic analogs (IDA) undergo the same metabolism as bilirubin and organic
      anions. After hepatocyte uptake, IDA analogs are excreted in the biliary tree and
      eliminated in the intestine. Technetium-99m-labeled IDA analogs provide liver and
      biliary tract images showing a progression from uptake to elimination. Several
      clinical applications are now available for the investigation of liver or biliary
      diseases. Hepatobiliary scintigraphy is particularly sensitive and highly
      specific to identify biliary atresia, acute cholecystitis and bile leak. It can
      also be also performed as a liver function test. It is the only technique
      providing real-time assessment of bile progression from the liver to the
      intestine.

PMID- 8554277
TI  - [Complex coronary reconstructions using the internal mammary artery. Technique of
      surgical angioplasty, preliminary results].
AB  - A technique of coronary surgical angioplasty is described. The long arteriotomy
      of the coronary artery over the stenosis is closed with the Internal Thoracic
      Artery (ITA) giving an enlargement patch effect. The majority of the atheromatous
      plaque is excluded from the lumen of the anastomosis and placed outside the
      suture line. The origin of the collateral arteries is preserved in the vascular
      lumen. The remodeled coronary artery is composed of a small gutter of native
      coronary artery and the whole surface of the ITA wall. In some cases, it is
      useful to associate a limited endarterectomy with the angioplasty. 66 surgical
      angioplasties have been performed in extensive coronary disease. Operative
      mortality was 5.4% with a myocardial infarction rate of 5.4%.

PMID- 8554278
TI  - [Repair of a left ventricular rupture after mitral valve replacement].
AB  - A 70-year-old patient (NYHA IV), who required a Carpentier pericardial prosthetic
      valve for mitral valve replacement, developed a type 2 intraoperative left
      ventricular rupture (mid portion of left ventricle) with cataclysmic bleeding. A
      successful repair with intraventricular dacron patch was performed by suturing
      the patch on the prosthetic sewing ring and through the ventricular wall using
      pledgetted stitches. The postoperative course was satisfactory without extensive
      myocardial necrosis and the patient is well 7 months later without angina and
      with reduced dyspnoea (NYHA II). Pre and postoperative left ventricular function
      were similar. These ventricular injuries after mitral surgery are well known but
      always difficult to manage and characterized by a high mortality rate. This
      technique (including prosthetic valve removal and intraventricular repair) seems
      to provide a greater chance of success than other external repair techniques. The
      best treatment remains prevention and consists in preserving the posterior mitral
      leaflet, avoiding extensive decalcification or resection and using low profiled
      prosthetic mitral valves. Likewise, mitral repair must be attempted as often as
      possible, because, in our opinion, this complication has never been reported in
      conservative mitral surgery.

PMID- 8554279
TI  - [Surgical treatment of aneurysms of the left ventricle. Immediate and long-term
      results. Apropos of a consecutive series of 121 cases].
AB  - From 1978 to 1992, 121 cases of postinfarction left ventricular aneurysm (99
      males, 22 females, mean age 60 years) were operated on. The authors insist on a
      high rate of clinical arhythmogenicity (31.4%) and associated mechanical
      complications (21%). 76% of patients were in functional NYHA class III or IV.
      Resection was performed in 90% of patients, plication in 10%. 58% underwent
      coronary artery bypass grafting (1.7 graft/patient), 16% encircling
      ventriculotomy, 8% mitral valve replacement and 13% closure of ventricular septal
      defect. Operative mortality was 14.9% (10% when other mechanical complications
      where excluded). 5-year survival is 67.9%. Late cardiac deaths are as follow:
      left ventricular failure (1.8% A/P), Sudden death (1.4% A/P), Myocardial
      infarction (0.6% A/P). 82% of survivals are in functional NYHA class I or II.
      Only functional class NYHA III or IV is predictive of late death. We conclude
      that postinfarction left ventricular aneurysm remains a high risk complication
      especially when associated with other mechanical complications. When
      arhythmogenicity is present we suggest rhythmologic surgery and in all cases,
      complete revascularization.

PMID- 8554280
TI  - [Distribution of cardioplegia by retrograde approach. Cannula of retrograde
      cardioplegia with manually inflating balloon versus self-inflating balloon].
AB  - Retrograde cardioplegia is still debated due to heterogeneous left ventricular
      flow distribution. The purpose of this study was to compare retrograde flow
      distribution delivered through the coronary sinus with two patterns of cannula.
      Fifty four patients were prospectively randomized to receive cold crystalloid
      retrograde coronary sinus cardioplegia with lither a manual inflating balloon
      cannula (group I, 24 patients) or a self-inflating balloon cannula (group II, 30
      patients). Left ventricular distribution of the cardioplegic solution was
      assessed by monitoring the left ventricular wall temperatures (anterior and
      posterior). The cardioplegic retrograde infusion was stopped as the anterior wall
      temperature reached 12 degrees C. In group II, 70.8% of patients had an identical
      cooling in the anterior and posterior wall of the left ventricle, versus 40.9% in
      group I (p < 0.05). The mean temperature difference between anterior and
      posterior wall was 2.9 degrees C (standard deviation: 2.9 degrees C) in group II
      versus 5.7 degrees C (standard deviation: 4.3 degrees C) for group I (< 0.05).
      The retroplegia cannula with the self-inflating balloon allows a better
      distribution of the cardioplegia flow than the manually inflating balloon. We
      think that this is due to the shape of the self-inflating balloon which more
      closely fits the morphology of the coronary sinus.

PMID- 8554281
TI  - [Video-assisted thoracic surgery with mini-thoracotomy: limits and indications].
AB  - Video-assisted thoracic surgery (VATS) combines a 5 cm mini-thoracotomy and
      videoscopic control using a camera. This technique is designed to reduce surgical
      invasiveness. From January 1993 to March 1994, we operated on 60 patients by 61
      VATS. The conversion rate to classical thoracotomy was 8%. The cases treated
      included 18 lung cancers, 20 cases of pulmonary emphysema, 6 cases of non
      malignant pulmonary nodules, 2 cases of bronchectasies and 10 operations on the
      pleura, pericardium or thoracic sympathetic nerves. We performed 12 lobectomies,
      24 atypical segmentectomies and 10 other operations. The hospital mortality rate
      was 2/60 (3.5%), the mean thoracic drainage duration was 3.2 days, and the mean
      hospital stay was 9.2 days. VATS provides certain analgesic and esthetic benefits
      but the functional benefit must be studied in more detail. VATS can be applied to
      segmentectomies and lobectomies for T1 or T2 lung cancers; but the benefits
      relating to malignancy must be precisely identified by long-term studies.

PMID- 8554282
TI  - [Results of repeated pulmonary resection in new homolateral neoplastic
      localization after conservative resection].
AB  - From 1978 through 1992, 93 patients with a previous lobectomy for bronchogenic
      cancer were referred for homolateral cancer recurrence. Forty-six patients were
      contraindicated for carcinologic reasons (30 stage IIIb and 16 stage IV). Forty
      seven patients (50.5%) were resectable, but 17 did not undergo surgery for
      associated medical problems (n = 11) or refusal (n = 6). The remaining 30
      patients form the population of the present study: 29 males and 1 female; mean
      age of 61 years (range 47-72). The previous cancer was stage I in 26 and stage II
      in 4. The mean interval between the 2 cancer diagnoses was 30 months (range 6
      97). Three patients underwent an exploratory thoracotomy (10%): 2 had mediastinal
      involvement and 1 had pleural metastases. Twenty-two (73%) underwent a completion
      pneumonectomy, and 5 had miscellaneous conservative resections. There were 4
      operative deaths (13%): one intraoperative bleeding, 1 postoperative bleeding, 1
      pulmonary embolism, 1 pneumonia. Four patients had nonfatal surgical
      complications: 2 clottings (reexploration), 1 empyema (lavage) and 1
      bronchopleural fistula (thoracoplasty). Resected patients were staged as follows:
      13 stage I, 4 stage II, 10 stage III. Survival following resection including
      operative mortality at 3 an 5 years was estimated as 52.5% and 44% for the whole
      series (72% for stage I). We conclude that repeat surgery conveys an increased
      risk, but may achieve valuable long-term results.

PMID- 8554283
TI  - [Contribution of an induction treatment in the surgical treatment of locally
      advanced non-small-cell cancers].
AB  - From October 1988 to July 1990, 18 patients with marginally resectable non-small
      cell cancer (10 stage IIIa and 8 stage IIIb) were entered in a phase-II trial
      combining induction therapy with a subsequent thoracotomy. Induction therapy
      included 2 courses of chemotherapy (5-FU and cisplatinum) and radiotherapy (30
      Gray in split course). Partial response was observed in 10 patients, and minimal
      response in 3. Thoracotomy disclosed unresectability in 3 patients. Fifteen
      complete resections consisted in 1 lobectomy and 14 pneumonectomies. There were
      no operative deaths (30 days). Postoperative recovery was uneventful in 3
      patients with exploratory thoracotomy and in 1 patient with lobectomy. Following
      pneumonectomy, we observed 2 bronchopleural fistulae and 1 empyema. On pathology,
      10 patients were stage IIIa, and 3 were stage I, whereas no residual tumor was
      found in 2 patients. During follow-up, local recurrence occurred in 2, and
      metastases in 8. On December 31st, 1993, 3 patients were alive at 44, 52, and 62
      months respectively. Nine patients had died from cancer, and 3 from unrelated
      causes. Estimated survival was 66.7% at 1 year, 33.3% at 3 years, and 20% at 5
      years. We conclude that induction therapy allowed satisfactory resection for
      marginally resectable tumors. Operative morbidity was increased in this group.
      However, the 5-year survival was similar to resectable stage IIIa cancer.

PMID- 8554284
TI  - [Emergency lung resections for invasive aspergillosis in neutropenic patients].
AB  - Mortality due to Invasive Pulmonary Aspergillosis (IPA) remains high in
      neutropenic patients due to pulmonary haemorrhage. The aim of this study was to
      evaluate the emergency surgical management of IPA. Seven neutropenic patients,
      with a mean age of 47 years (range: 30-64) (4 women and 3 men) were treated for
      (6 cases) acute leukaemia one Myeloma (1 case). Presumptive diagnosis of IPA was
      based on: Halo sign (n = 6) or air-crescent sign (n = 1) on CT scan, positive
      serology (n = 4), positive antigenemia (n = 3) and positive broncho-alveolar
      lavage (n = 1). In 2 cases, IPA diagnosis was only based on CT scan. In all
      cases, aspergillosis lesions were located near the left (n = 5) or right (n = 2)
      pulmonary artery. The type of pulmonary resection was: left superior lobectomy in
      3 cases, left superior lobectomy and Fowler's segmentectomy in 1 case, Left
      inferior lobectomy in 1 case, right superior lobectomy in 1 case and middle
      lobectomy and paracardiac segmentectomy. Sleeve resection of the pulmonary artery
      was performed in two patients. There were no deaths or major postoperative
      complications. Mean hospital stay after surgery was 12 days (rang: 8-19).
      Histological examination confirmed the diagnosis of IPA. CT is essential to
      determine the optimal timing for surgery.

PMID- 8554285
TI  - [Increased association of cardiac and thoracic vascular lesions after closed
      trauma of the thorax].
AB  - The association of a cardiac and a thoracic vascular lesion following blunt
      trauma seems real based on our experience and other published reports. Over the
      last 4 years, we have operated upon 3 patients with this association. The cardiac
      lesions included severe myocardial contusion (documented by electrocardiographic
      and enzymatic changes), a tear of the aortic valve, and occlusion of a coronary
      artery. The vascular lesions consisted in rupture of the aortic isthmus in 2
      patients and traumatic pseudoaneurysm of the innominate artery. This association
      justifies a detailed cardiovascular evaluation in any case of severe cardiac or
      thoracic vascular lesion.

PMID- 8554286
TI  - [Upper thoracic sympathectomy by thoracoscopic approach. A method of choice for
      the treatment of palmar hyperhidrosis].
AB  - Palmar hyperhidrosis is excessive sweating beyond physiological needs in the palm
      without recognized etiology. Although a benign disease, it is annoying to most
      patients. Currently the best treatment for this condition is upper thoracic
      sympathectomy via many different approaches. The video-thoracoscopic approach has
      been recommended a a minimally invasive procedure. We report our 1-year
      experience with transaxillary endoscopic sympathectomy in 99 patients with palmar
      hyperhidrosis. Standard video-laparoscopy was used via a transaxillary approach
      to perform sympathectomy. The mean operating time of this operation was 12
      minutes and mean hospital stay was 32 hours. The results in terms of warm and dry
      hands were excellent. Only one case of transitory Horner syndrome was noted.
      Transaxillary thoracoscopic sympathectomy for palmar hyperhidrosis is a
      relatively simple and effective procedure which can be performed with standard
      laparoscopic instruments. The advantages are, short recovery time and hospital
      stay along with excellent functional and cosmetic results. We are convinced that
      thoracoscopic sympathectomy is the procedure of choice for the treatment of
      palmar hyperhidrosis.

PMID- 8554287
TI  - [Early reoperation in chylothorax after thoracic surgery].
AB  - Chylothorax is a rare complication of thoracic surgery. The chyle leak can induce
      serious metabolic and immunological disorders. The ideal treatment of chylothorax
      has not been clearly established, and opinions are still divided between medical
      treatment and early or late surgical reoperation after prolonged medical
      treatment. Out of a total of 1.750 thoracic operations performed at the Centre
      Chirurgical du Val d'Or over the last 10 years, six cases of chylothorax were
      reoperated early, an average of five days after the initial operation. The chyle
      leak was easy to localize in every case. The second operation was performed via
      the same initial incision. All six patients has an uneventful postoperative
      course and only one case had a persistent chyle leak which gradually resolved.
      The mean total hospital stay was 18 days. No systemic infections or deaths were
      recorded. Early reoperation avoids the complications of prolonged medical
      treatment, is technically easy and decreases the length of hospital stay.

PMID- 8554288
TI  - 8th International Hamburg Symposium on Tumor Markers. Hamburg, Germany, December
      3-5, 1995. Abstracts.

PMID- 8554289
TI  - [The use of the intestine in urologic surgery].

PMID- 8554290
TI  - [Augmentation enterocystoplasty. Apropos of 15 cases].
AB  - We reviewed the efficacy of augmentation enterocystoplasty about 15 cases, based
      on technical modalities and intestinal loop used. There were 10 tuberculosis
      bladders, 2 bilharzial bladders, 2 interstitial cystitis and one neurogenic
      bladder. We used for bladder augmentation the sigmoid (7 cases), ileum (6 cases)
      and coeco-ileum (2 cases). Ureteroileoplasty is associated in three cases for
      large tuberculous ureteral stenosis, and reimplantation of ureter in the
      neobladder is realised in seven cases. The results with detubularized ileum were
      excellent. We observed in one patient persistence of dilatation of upper urinary
      tract after use of detubularized sigmoid. The results with use of ileocoecum are
      poor. We observed good results by using detubularized ileum, so we prefer this
      intestinal loop than the others. There was no significative difference between
      different detubularisation technics. Reimplantation of ureter inneobladder is
      indicated when there is terminal ureteral lesions.

PMID- 8554291
TI  - [Cystectomy followed by cecocystoplasty: functional and oncologic results. An
      experience of 101 cases].
AB  - From 1979 to 1992, 101 radical cystectomy with caecoplasty were performed by the
      same operator (MR). Mean age of the patients was 62 years with a sex-ratio: 10
      males/1 female. The indications were: Transitional Cell Carcinoma in 89 cases,
      neurologic bladder in 5 cases, interstitial cystitis in 3 cases tuberculosis
      bladder in 3 cases and lymphoma in one case. The operative mortality was 3% and
      postoperative morbidity was 8%. The surgical procedure consisted of performing a
      neo-bladder with ileocaecal segment. The technique of ureterocaecal implantation
      changed during the study period. On a functional point of view, 28 ureterocaecal
      stenosis were reported (15%). It were rare (2.4%) with the last ureterocaecal
      anastomosis technique. The diurnal continence rate was 100%. The nocturnal
      continence rate was only 25%. On uroflowmetric point of view, the
      detubularization permitted to obtain low pressure bladders with 15% rate of
      atonic bladder. Transverse taeniamyotomy of the caecum permitted to increase the
      uroflowmetric performance of the bladder without atonic risk. The 5 and 10 year
      overall actuarial survival rate were respectively 5% and 30%. Tumoral stage was a
      significant prognostic factor. An adjuvant chemotherapy was performed in 28
      patients. The 5 year actuarial survival rate of the patients with a chemotherapy
      was 82% versus 28% for the patients without chemotherapy (p < 0.01).
      Caecocystoplasty after radical cystectomy was a reliable technique in our
      experience.

PMID- 8554292
TI  - [Continent urostomy using the intestine].
AB  - The hydraulic ileal valve, which we developed in 1975, ensures continence by
      adapting to 5 different urinary reservoirs. An isolated ileal segment (14 cm) is
      folded inward on itself throughout its entire length. We performed 260 continent
      urostomies. An ileocecal reservoir was used in 179, detubularised ileocecal
      reservoir in 32, ileum 34, sigmoid 5, rectum 1 and bladder (continent cystostomy)
      in 8. Of the patients 82% were continent immediately. Continence was obtained
      after repair of the valve in 12.5% therefore, 94.5% patients over all were
      continent.

PMID- 8554293
TI  - Transformation of the Bricker to a continent urinary reservoir to eliminate
      severe complications of uretero-ileostomy performed in eight patients among 200
      Bricker.
AB  - Between 1969 and 1994 urinary diversion via the ileal loop (Bricker's operation)
      was performed in 200 patients. After introduction of methods of continent urinary
      diversion into clinical practice, some of young patients operated in childhood
      for congenital lower urinary tract malformations demanded the conversion of the
      primary diversion. The decision was influenced, however, not only by subjective
      complaints but also by severe complications having relation to the long-lasting
      presence of stoma. A modified Mainz pouch I, with a catheterizable stoma was
      constructed in 6 patients with primary uretero-ileostomy made 7 to 22 years prior
      to conversion because of exstrophy of the urinary bladder or a neurogenic bladder
      with total urine incontinence. The ileal loop used for uretero-ileostomy was
      detubularized or combined with additional segments of ileum and colon. The ileal
      stoma was connected to the umbilicus. In other two patients suffering from a
      neurogenic bladder the uretero-ileostomy was converted to an orthotopic ileal
      pouch. The authors present long-term results (1.5 to 7 years) of follow-up with
      urodynamic and radiological evaluation. The results both compensate the
      urologist's efforts and enhance the patient's quality of life.

PMID- 8554294
TI  - [The continent ileocecal pouch. The Mainz pouch I].
AB  - Since 1993 to July 1994, 374 patients underwent a Mainz Pouch procedure in their
      hospital. The follow up is between 4.2 +/- 2.6 years. The authors used this
      technique as well for bladder augmentation, bladder substitution as continent
      diversion. If possible, the appendix will be used for creating the continence
      system.

PMID- 8554295
TI  - [The rectosigmoid pouch. The Mainz pouch II. Apropos of 73 cases].
AB  - The Mainz Pouch II, a low pressure rectosigmoid reservoir for urine is created
      without any bowel anastomosis. Antimesenteric opening of the intestine at the
      rectosigmoid junction and subsequent wide-to-side anastomosis are performed.
      Without the risque of damaging the mesentery blood supply, the pouch is fixed at
      the area of the pomontory or the psoas muscle to avoid the kinking of the
      ureteres and consecutive dilatation of the upper tract.

PMID- 8554296
TI  - Our experience with the Mainz pouch II: 40 patients; follow-up and complications.
AB  - Authors used the Mainz pouch II technique for urinary diversion in 40 patients
      suffering from bladder cancer. They made minor modifications to the original
      surgical technique: a longer, 40 cm bowel is detubularized, the ureters are
      pulled through the mesosigma and embedded in a groove of the bowel's mucosa, the
      sigma pouch is fixed to the dorsal peritoneum, a straight suture is used. Single
      row on the dorsal wall and two-rows on the ventral wall. Within a few days after
      the surgery suture insufficiency occurred in the abdominal wall in 5 cases, in
      the bowel in 2 cases. To treat suture disrupture of the bowel authors transformed
      the pouch, added a newly detubularized bowel segment to create a spheric rectum
      pouch and performed a definitive colostomy. During the follow-up period of six
      months to four years 8 of the 40 patients died from bladder cancer, 2 from
      cardiac failure, 1 from pulmonary embolism, and 6 have had a recurrence of the
      tumor. In the 23 tumor free patients we found no reflux, one has a slight
      stenosis of the ureter, febrile pyelonephritis did not occur, the pouch did not
      slip, the ureter had no kinking, and all patients are continent. Hyper-chloraemic
      acidosis has been prevented by regular administration of sodium bicarbonate or
      kalium citrate. Authors believe that Mainz pouch II is to be the most appropriate
      continent urinary diversion if an orthotopic substitution is not possible.

PMID- 8554297
TI  - [Uretero-colonic implantation in children. Late results].
AB  - An uretereo-colic anastomosis in children is performed in three occasions: 1) The
      trans-intestinal cutaneous ureterostomy (Bricker) has a low rate of complications
      concerning ureterocolic anastomosis. Nevertheless, occurrence of pyelonephrites
      may oblige to perform an anti-reflux procedure. 2) Implantation of ureters in the
      intestinal segment of an augmentation colocystoplastys in unusual; when
      necessary, this type of implantation is safe because colon is appropriate for an
      antireflux procedure. 3) Ureterocolic diversion (Coffey) is quite comfortable for
      patients. Risks of renal failure and of adenocarcinoma are minimal thanks to an
      annual control. Concerning exstrophy of bladder, it seems now that risk of
      infertility is lower for patients with an ureterocolic diversion than those with
      a genito-urinary reconstruction.

PMID- 8554298
TI  - [Simplified urinary diversion in colostomized patients].
AB  - The authors report 3 cases of urinary diversion in patients with preexisting
      colostomy and operated by technique of Noble and Davis. The previous colostomy is
      used for urinary diversion and new colostomy is created for fecal diversion. This
      method is simple, time-saving and very beneficial for high risk patients. We
      found it very useful and had gave us satisfactory results.

PMID- 8554299
TI  - [Urinary diversion surgery of the ureter of a single functioning kidney].
AB  - During a 10 years period at the Department of Urology of the Surgical Clinic KBC
      "Bezanijska kosa" 32 patients were hospitalised with a single functional kidney,
      who were operated on and derivation operations of the ureter were performed. The
      reason for a derivating operation on the ureter was an infiltrative cancer of the
      urinary bladder in 24 patients. In 6 patients there was a recurrent vesico
      vaginal fistula and in two multiple purulent ureterocutaneous fistulas. Derivant
      operations on the level of the ureter with a bowel loop of the ileum was
      performed in 24 patients, by ileocoecal conduit in 6; a ureterosigmoidostomy was
      performed in two patients. The complications of these surgical interventions and
      the remaining life span of these patients after the operation are presented.

PMID- 8554300
TI  - Gastrocystoplasty, a wrong choice in an adult case.
AB  - A 28-year-old woman presented a huge vesico-vagino-rectal fistula after
      radiotherapy because of a gynecological tumour. Reconstruction consisted of a
      colostomy, closure of the rectal hole with a pedicled perineal skin graft, a
      bivalve opening of the bladder and, with the two valves coverage of the vaginal
      suture line, and augmentation gastrocystoplasty. The fistulas healed but the
      patient suffered from an intolerable burning sensation, that is why the stomach
      wall was removed and uretero-ileo-cutaneostomy was created. The colostomy was
      closed, and the patient now has a well functioning urine stoma.

PMID- 8554301
TI  - Oral Cephalosporins. Introduction.

PMID- 8554302
TI  - Systematics of beta-lactams: chemical properties and structure activity
      relationship of oral cephalosporins.

PMID- 8554303
TI  - Oral cephalosporins in upper respiratory infections.

PMID- 8554304
TI  - Oral cephalosporins: clinical results in lower respiratory tract infections.

PMID- 8554305
TI  - Oral cephalosporins: clinical results in urinary tract infections.

PMID- 8554306
TI  - Tolerability of oral cephalosporins.

PMID- 8554307
TI  - Clinical pharmacokinetics of oral cephalosporins.

PMID- 8554308
TI  - Microbiology of oral cephalosporins.

PMID- 8554309
TI  - Pharmacology and toxicology of oral cephalosporins.

PMID- 8554310
TI  - Reductive modification and nonreductive activation of purified spinach
      chloroplast NADP-dependent glyceraldehyde-3-phosphate dehydrogenase.
AB  - Spinach chloroplast NAD(P)-glyceraldehyde-3-phosphate dehydrogenase (NAD(P)
      GAPDH; EC, 1.2.1.13) was purified as the 600-kDa oligomer of low specific
      activity. Incubation of the enzyme with either a reductant or a 1,3
      bisphosphoglycerate (1,3bisPGA) generating system, but most effectively with
      both, resulted in an increase of the apparent NADPH-dependent activity. Only the
      1,3bisPGA treatment caused dissociation and yielded the 150-kDa heterotetramer
      (A2B2). The higher activity of the tetramer is largely due to a decreased KM
      value for the substrate 1,3bisPGA. Reductive treatment alone does not dissociate
      the enzyme. Reduction was equally effective with glutathione as with
      dithiothreitol or with reduced thioredoxin f. The concentration of 1,3bisPGA
      required to obtain 50% activity (K alpha) was 19.5 +/- 4.1 microM for the
      untreated enzyme and 2.0 +/- 1.4 microM for the thiol-pretreated enzyme. Thus, in
      vitro 1,3bisPGA, alone or--at much lower concentrations--together with a
      reductant can activate (and dissociate) NAD(P)-GAPDH. The enzyme exhibits similar
      K alpha values in its reduced and its oxidized form for ATP (1-2 mM), NADP (50
      200 microM), and NADPH (0.3-0.5 mM) as positive effectors, but these effectors do
      not lead to any activation when present together with 0.14 mM NAD. Only 1,3bisPGA
      retained its characteristic effect in the presence of NAD. The dissociated enzyme
      reaggregates upon removal of the positive effectors. From these results it is
      concluded (i) that the role of the reduction of the NAD(P)-GAPDH in vivo is to
      increase its sensitivity toward the activator 1,3bisPGA and (ii) that the actual
      activation (and aggregation) state of the enzyme in chloroplasts in the light is
      regulated by the concentration of 1,3bisPGA as activator in the stroma and its
      actual activity by the availability of 1,3bisPGA as substrate.

PMID- 8554311
TI  - G-protein-sensitive guanylyl cyclase activity associated with plasma membranes.
AB  - A mammalian plasma-membrane-bound guanylyl cyclase is inhibited by NaCl and this
      inhibition is dependent on GTP concentrations and independent of the chloride
      salt type. This chloride inhibition is reversed by GTP analogs such as GTP gamma
      S, suggesting the involvement of G proteins. When the ability of bacterial toxins
      to affect this chloride-sensitive guanylyl cyclase was examined, pertussis toxin
      decreased the basal activity and the chloride sensitivity was greatly reduced.
      Cholera toxin induced a slight activation of the basal activity, without
      significant changes in the NaCl inhibition. These data indicate that G proteins
      regulate the chloride sensitivity of this guanylyl cyclase activity. Another
      property described here is the ability of ATP and analogs to inhibit the basal
      activity. However, these nucleotides did not modify the chloride sensitivity of
      the membrane-bound guanylyl cyclase activity.

PMID- 8554312
TI  - Substrate-induced translocation of PKC-alpha to the membrane.
AB  - The protein kinase C-alpha (PKC-alpha)-catalyzed phosphorylation of the peptide
      [Arg]4-Tyr-Gly-Ser-[Arg]5-Tyr is independent of Ca2+ and phospholipid. The
      binding of this peptide to PKC-alpha induces a conformational change in the
      enzyme that results in the exposure of hydrophobic groups that subsequently
      insert into a membrane. Induction of a conformational change in the enzyme by
      this peptide is demonstrated by susceptibility to trypsin cleavage. Additionally,
      exposure of hydrophobic sites on the enzyme is shown by the binding of the
      fluorescent probes PRODAN and bis-ANS and by the partitioning of the enzyme into
      a Triton X-114-enriched phase. In the presence of a phospholipid bilayer
      containing phosphatidylserine, this peptide promotes the translocation of PKC
      alpha to the membrane in the absence of Ca2+ as observed by increased resonance
      energy transfer between Trp on the enzyme and dansyl-groups attached to the
      lipid, as well as by changes in the intrinsic tryptophan fluorescence of the
      enzyme. Also, once bound to the membrane the peptide.PKC-alpha complex undergoes
      further conformational change which is evident by an increased sensitivity to
      trypsin cleavage at the hinge region. These results demonstrate that substrate
      binding can also induce translocation of PKC to the membrane and suggest that the
      removal of the pseudosubstrate domain is coupled to a conformational change in
      the enzyme that results in the exposure of hydrophobic groups.

PMID- 8554313
TI  - Lens hydration in transgenic mice containing HIV-1 protease linked to the lens
      alpha A-crystallin promoter.
AB  - Two constructs of transgenic mice, TG61 and TG72, containing HIV-1 protease
      linked to lens alpha A-crystallin promoter develop cataract. The TG61 construct
      exhibits cataractogenesis in utero, while in the TG72 construct frank opacities
      appear 24 days (homozygotes) and 26 days (hemizygotes) after birth. Differential
      scanning calorimetry and thermogravimetric analysis studies indicate that the
      hydration of lenses is strongly correlated with cataractogenesis. In all clear
      lenses (normal and precataractous) the total water content was the same, 68%, and
      increased upon opacification. The bound water, measured as percentage
      nonfreezable water of the total water, decreased upon cataract formation,
      indicating a syneretic process. On the other hand, the bound water expressed as
      grams of nonfreezable water per gram dry weight increases upon opacification.
      This implies that proteolysis and subsequent enhanced hydration is the primary
      supramolecular event in cataractogenesis and that syneresis in the lens of
      transgenic mice is of secondary importance.

PMID- 8554314
TI  - Novel 3,4-di- and 3,4,5-trihydroxyphenylalanine-containing polypeptides from the
      blood cells of the ascidians Ascidia ceratodes and Molgula manhattensis.
AB  - Acetic acid urea extraction of the blood cells of two ascidian species yielded
      four novel families of polypeptides (3500-5300 Da) containing 3,4
      dihydroxyphenylalanine (DOPA) and 3,4,5-trihydroxyphenylalanine (TOPA) from the
      Phlebobranch Ascidia ceratodes and two DOPA proteins (9-10 kDa) from the
      Stolidobranch Molgula manhattensis. 3,4,5-Trihydroxyphenylalanine residues have
      not been found previously in polypeptides in any biological system. The DOPA
      content of the M. manhattensis proteins is the highest yet reported for a
      naturally occurring DOPA protein. The successful isolation of proteinaceous
      components from A. ceratodes blood cells requires the incorporation of high
      concentrations of complexing agent in the extraction buffers to inactivate
      vanadium(III) which forms intractable organometallic polymers. The A. ceratodes
      blood cell polypeptides are all rich in alanine and TOPA residues, have neutral
      to basic pI values, and, while all give single bands on acid urea-polyacrylamide
      electrophoresis, they exhibit extensive microheterogeneity. This is reflected by
      their large molecular weight distribution as determined by matrix-assisted laser
      desorption ionization-mass spectrometry, the variation in the ratio of their 280
      nm absorption to chromophores of unknown structure in the polypeptide's
      electronic absorption spectra, and the N-terminal sequence analysis. The two M.
      manhattensis proteins consist largely of four amino acids (alanine, valine,
      phenylalanine, and DOPA) with DOPA accounting for upward of 40 mol%. Both give an
      N-terminus of Ala-Phe-Tyr before resisting further progress by Edman degradation.
      Proteins and polypeptides from both ascidians are extremely resistant to
      proteases, a property which, while hampering characterization by sequence
      analysis, appears ideally suited to their proposed function of forming an
      impervious hemostat at the site of vascular injury. The yield of proteins and
      polypeptides relative to tunichromes appears to be seasonally dependent. The
      presence of DOPA and TOPA moieties in the proteins and polypeptides implicates
      them, as well as the tunichromes, as potential metal-sequestering agents.

PMID- 8554315
TI  - Characterization of epitopes recognized by 4-hydroxy-2-nonenal specific
      antibodies.
AB  - In the present study, we have raised anti-peptide antibodies directed to the
      major membrane lipid peroxidation product 4-hydroxy-2-nonenal (HNE) attached
      covalently to histidine, and their specificities were compared with those of the
      polyclonal antibodies (anti-HNE-protein antibodies) raised against HNE-treated
      keyhole limpet hemocyanin (K. Uchida et al. (1993) Proc. Natl. Acad. Sci. USA 90,
      8742-8746). The anti-HNE-histidyl peptide antibodies (anti-HNE-histidine
      antibodies) were prepared by immunizing rabbits with a HNE-conjugated
      heptapeptide (Gly3-His-Gly3 amide) coupled to the carrier protein. The antisera
      were purified on an affinity gel prepared by covalent attachment of a HNE
      conjugated heptapeptide (Ala3-His-Ala3 amide). Among the structurally defined 4
      hydroxy-2-alkenal-amino acid adducts tested, binding of anti-HNE-histidine
      antibodies to the HNE-treated protein was not only inhibited by HNE-histidine,
      HNE-cysteine, and HNE-lysine, but also by 4-hydroxy-2-octenal-histidine and 4
      hydroxy-2-decenal-histidine adducts. Cross-reactivity studies revealed that both
      anti-HNE-protein antibodies had the highest affinity for the HNE-treated protein
      and that neither of the antibodies cross-reacted with the protein treated with
      aldehydes including malondialdehyde, 1-hexanal, 2-hexenal, or 2-nonenal. These
      results suggest that the dominant epitope recognized by antibodies is the 2
      CH3(CH2)n-5-hydroxytetrahydrofuran (n > or = 3) moiety of the Michael adducts.
      The immunohistochemical analysis of atherosclerotic lesions of human aorta
      demonstrated that these antibodies reacted strongly with granular cytoplasmic
      elements of foam cells and weakly with elements in the surrounding sclerotic
      stroma.

PMID- 8554316
TI  - Effect of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone on protein
      oxidation and life span.
AB  - N-tert-Butyl-alpha-phenylnitrone (PBN), a lipophilic spin-trapping compound, has
      been reported to decrease the concentration of protein carbonyls, the products of
      protein oxidation, in the brain of old gerbils to virtually the level found in
      the young gerbils (Carney, J. M., et al. (1991) Proc. Natl. Acad. Sci. USA 88,
      3633-3636). The validity of this finding as well as that of the commonly used 2,4
      dinitrophenylhydrazine procedure for the measurement of protein carbonyls was
      recently called into question by Cao and Cutler ((1995) Arch. Biochem. Biophys.
      320, 106-114). The objective of the present study was to examine some of the
      relevant issues such as (a) whether the original findings on the effects of PBN
      can be confirmed, (b) whether similar effects of PBN occur in other species and
      tissues, and (c) whether PBN affects the life span of animals. Results of this
      study provide confirmation of the original finding that PBN indeed causes a
      decrease in protein carbonyl content in the gerbil brain cortex. However, a
      similar effect is not observed in the gerbil heart or the mouse brain cortex.
      Effects of PBN on protein carbonyls are thus variable depending upon tissue and
      species. PBN administration did not extend the life span of houseflies and at
      relatively high concentrations it was found to be toxic.

PMID- 8554317
TI  - Cloning, expression, and characterization of (+)-delta-cadinene synthase: a
      catalyst for cotton phytoalexin biosynthesis.
AB  - In cotton, sesquiterpene phytoalexins are elicited in response to bacterial or
      fungal infection. A Gossypium arboreum cell suspension culture which produces the
      sesquiterpene phytoalexin gossypol showed a time-dependent 10-fold increase in a
      1.9-kb mRNA in response to a challenge by a preparation from Verticillium
      dahliae. The mRNA prepared from these elicited cultures was used to isolated two
      cDNA clones that contain open frames coding for proteins of 554 amino acids with
      M(r) 64,096 and 64,118. The encoded protein shows a significant degree of
      sequence identity with the other known plant terpene cyclases. Western blot
      analyses with a cross-reactive monoclonal antibody from a related sesquiterpene
      synthase in Nicotiana tabacum showed a time-dependent increase of a 65-kDa
      protein which reached a maximal level 24 h post elicitor treatment. The encoded
      protein from the pXC1 cDNA was produced in Escherichia coli and purified by
      affinity column chromatography. The enzymatic properties of this protein were
      identified by a radiochemical assay for cyclization of farnesyldiphosphate and a
      product structure was assigned by GC-MS, chiral phase GC, and NMR analyses as (+)
      delta-cadinene. The fungal-elicited production of a (+)-delta-cadinene synthase
      is consistent with a role for this enzyme as the first committed step in the
      pathways leading to the related phytoalexins gossypol and lacinilene C in cotton.

PMID- 8554318
TI  - Identification and analysis of drug-responsive expression of UDP
      glucuronosyltransferase family 1 (UGT1) isozyme in rat hepatic microsomes using
      anti-peptide antibodies.
AB  - Expression of rat hepatic UDP-glucuronosyltransferase family 1 (UGT1) isozymes
      has been examined using anti-peptide antibodies raised against a conserved
      carboxyl-terminal portion of all isozymes and variable amino-terminal portions of
      each isozyme of the phenol cluster (UGT1A) and bilirubin cluster (UGT1B). Among
      the isozymes expressed in rat hepatic microsomes, UGT1B1 (54 kDa) of bilirubin
      cluster was found to be a major form and minor forms were identified as UGT1A1
      (53 kDa), UGT1B2 (56 kDa), and UGT1B5 (57 kDa). Using a combination of 2D sodium
      dodecyl sulfate gel electrophoresis and immunoblotting, all the isozymes were
      found to be simultaneously lacked in Gunn rat hepatic microsomes. The effects of
      various drugs as inducer on the expression of each UGT1 isozyme were analyzed.
      The UGT1A1 and UGT1A2 of the phenol cluster isozymes were significantly induced
      in 3-methylcholanthrene-treated rats. The expression of UGT1B1 and the
      glucuronidation activity toward bilirubin in rat hepatic microsomes were induced
      two- to threefold by clofibrate and dexamethasone administration. On the other
      hand, the regulation of UGT1B2 and UGT1B5 expression was different from that of
      UGT1B1. These results clearly show the drug-responsive expression of each UGT1
      isozyme using isozyme-specific antibodies for the first time.

PMID- 8554319
TI  - Characterization of the antifungal protein secreted by the mould Aspergillus
      giganteus.
AB  - An antifungal polypeptide (AFP) of 51 amino acid residues, secreted by the mould
      Aspergillus giganteus, has been purified to homogeneity and characterized. The
      inhibitory effect of this protein on the growth of different microorganisms has
      been studied. Whereas the growth of many of the filamentous fungi assayed is
      inhibited, no effect has been observed against yeasts or bacteria. The minimal
      concentration for total inhibition of the growth is in the range 6 to 25 microM.
      The antifungal polypeptide does not produce any effect on the growth of the
      producing mould. The polypeptide promotes aggregation of acidic phospholipid
      vesicles. A remarkable resistance to proteolysis and a low hydrogen x deuterium
      exchange have been observed for this protein. The protein does not show any
      thermal transition up to 80 degrees C when studied by differential scanning
      calorimetry and infrared spectroscopy. The uv absorbance, fluorescence emission,
      and circular dichroism (CD) characteristics of this protein have been studied.
      The protein exhibits a strong positive band at 230 nm as a prominent feature of
      the CD spectrum in the far uv region. All the spectroscopical properties of the
      antifungal protein are highly influenced by the abundance of tyrosine residues.
      These can be grouped in two different populations, buried and exposed, based on
      the results of pH-titration experiments. Fourier-transform infrared spectroscopy
      reveals a high content of beta-structure in AFP. Reduction and carboxy
      amidomethylation produces a rather unstructured polypeptide as deduced from its
      spectroscopical properties.

PMID- 8554320
TI  - Role of cytochrome b5 in NADH-dependent microsomal reduction of ferric complexes,
      lipid peroxidation, and hydrogen peroxide generation.
AB  - The NADH-dependent microsomal electron transfer system consists of NADH
      cytochrome b5 reductase and cytochrome b5, which donates reducing equivalents to
      fatty acyl desaturase, cytochrome P450, and other reactions. A study was carried
      out to investigate the interaction of NADH with several ferric complexes and to
      evaluate the role of cytochrome b5 in these interactions. NADH-dependent
      microsomal lipid peroxidation was stimulated by ferric-ATP, ferric-histidine, and
      ferric-ammonium sulfate, but not by ferric-EDTA. Anti-cytochrome b5 IgG produced
      a concentration-dependent inhibition of lipid peroxidation catalyzed by all three
      ferric complexes. Addition of purified cytochrome b5 to the microsomes increased
      the rate of lipid peroxidation with all three ferric complexes. Lipid
      peroxidation in control and the cytochrome b5-fortified microsomes was not
      sensitive to superoxide dismutase, catalase, or DMSO and was completely inhibited
      by trolox and propylgallate. Ferric-EDTA stimulated NADH-dependent microsomal
      production of H2O2 and NADH consumption. Anti-cytochrome b5 IgG had only a small
      inhibitory effect on this stimulation by ferric-EDTA. NADH supported microsomal
      reduction of ferric complexes in the order ferric-ATP > ferric-histidine
      approximately ferric-ammonium sulfate > ferric-EDTA. Anti-cytochrome b5 IgG
      inhibited, whereas added cytochrome b5 stimulated, the reduction of ferric-ATP,
      ferric-histidine, and ferric-ammonium sulfate, whereas reduction of ferric-EDTA
      was not affected by these additions. Ferric-ATP, at high concentrations, was more
      effective than ferric-histidine or ferric-ammonium sulfate in stimulating lipid
      peroxidation and in becoming reduced by NADH-dependent microsomal electron
      transport; anti-cytochrome b5 IgG was less inhibitory and added b5 was less
      stimulatory at 50 microM ferric-ATP compared to 5 microM ferric-ATP or 50 microM
      ferric-histidine or 50 microM ferric-ammonium sulfate. It is concluded that
      cytochrome b5 is required for reduction of low and high concentrations of ferric
      histidine and ferric-ammonium sulfate and low concentrations of ferric-ATP and
      for the lipid peroxidation catalyzed by these ferric complexes. The reductase,
      not cytochrome b5, is involved in interaction with ferric-EDTA. Higher
      concentrations of ferric-ATP can also interact with the reductase, as well as
      with cytochrome b5.

PMID- 8554321
TI  - Response of purified mitochondrial DNA topoisomerase I from bovine liver to
      camptothecin and m-AMSA.
AB  - The type I DNA topoisomerase isolated from bovine liver mitochondria is
      demonstrated here to be inhibited by camptothecin, a plant alkaloid previously
      shown to target the nuclear type I topoisomerase in mammalian cells. The
      antitumor drug reduces the ability of the mitochondrial enzyme to relax positive
      as well as negative supercoils although the inhibition of the former process
      requires more than 60-fold more drug than the latter process. A similar response
      is seen with the nuclear topoisomerase I. Camptothecin also stimulates the
      mitochondrial topoisomerase-induced cleavage of pUC19 at numerous, discrete
      sites. The antitumor drug 4'-(9-acridinylamino)-methanesulfon-m-anisidide, which
      has been shown to target the nuclear topoisomerase II, inhibited the
      mitochondrial type I topoisomerase relaxation activity, but this effect was found
      to be the result of the drug intercalating into the negatively supercoiled DNA
      rather than from a specific interaction with the mitochondrial enzyme. VM-26, a
      nonintercalating topoisomerase II poison, showed no inhibitory effect up to a
      concentration of 50 microM.

PMID- 8554322
TI  - Glucose induces amphiphilic to hydrophilic conversion of a subset of glycosyl
      phosphatidylinositol-anchored ectoproteins in yeast.
AB  - Previously, we have studied the lipolytic cleavage of a glycosyl
      phosphatidylinositol (GPI)-anchored plasma membrane protein in yeast in response
      to a physiologically relevant external signal, i.e., transfer of spehroplasts
      from lactate to glucose medium (cf. Muller and Bandlow (1993) J. Cell. Biol. 122,
      325-336). In the present study the glucose-induced lipolytic processing of myo
      [14C]inositol-labeled total GPI proteins of the plasma membrane and in particular
      of two such proteins, Gas1p and Gce1p, was examined in yeast spheroplasts. It was
      found that a small number of GPI proteins, among them Gce1p, are readily cleaved,
      whereas Gas1p and the majority of the GPI proteins are relatively little
      affected. Glucose-induced processing of Gce1pcould be demonstrated also in intact
      cells. Increased GPI cleavage after exposure of cells or spheroplasts to glucose
      is not due to stimulation of cell surface expression of Gce1p, as the amount of
      total GPI-anchored Gce1p bound to plasma membranes is comparable in cells grown
      in glucose or lactate. In agreement with this, Brefeldin A added together with
      the label blocks transport of newly made Gce1p to the cell surface and, in the
      consequence, cleavage of labeled Gce1p in spheroplasted yeast cells. (The drug is
      ineffective in intact cells). On the other hand, Brefeldin A does not
      significantly affect glucose-induced processing of inositol-labeled Gce1p at the
      plasma membrane when present during the period of nutritional upshift. We discuss
      that addition of glucose to the cells leads to the activation of a GPI-specific
      phospholipase which accepts only a subset of GPI proteins as substrates. This
      interpretation is additionally corroborated by the finding that purified
      [14C]inositol-labeled Gcep1p is lipolytically cleaved when incubated with Triton
      X-100-insoluble membrane complexes isolated from glucose-induced but not from
      uninduced spheroplasts. It is concluded that the phospholipase is present in
      these complexes and its state of activity is preserved during the preparation.
      GPI anchor cleavage in yeast appears to resemble strikingly the situation in
      insulin-responsive adipocytes subsequently to stimulation by insulin of glucose
      transport into these cells.

PMID- 8554323
TI  - The concentration of cellular nitrogenase proteins in Azotobacter vinelandii
      whole cells as determined by activity measurements and electron paramagnetic
      resonance spectroscopy.
AB  - The concentration of MoFe protein (Av1) in Azotobacter vinelandii whole-cell
      crude extract was measured by electron paramagnetic resonance spectroscopy at g =
      3.7 resonance. The Av1 concentration was also measured from the activity of crude
      extract to which increasing amounts of purified Av1 and Av2 were added. The Av2
      concentration was determined by fitting activity measurements of crude extract
      and crude extract to which purified Av2 was added. The Av1 concentration was
      found to be 26-28 microM and that for Av2 was 42-45 microM in whole cells, with a
      Av2/Av1 ratio of 1.6. In vitro activity measurements carried out as a function of
      Av1 concentration at Av2/Av1 ratios of 1 and 4 showed a dilution effect below
      0.08 microM, a factor of 2 below that observed for nitrogenase reactivity for
      Klebsiella pneumoniae. No deviations from linearity were observed up to 26 microM
      for the Av1-Av2 interaction. The flavoprotein (AvFlp) was shown to enhance
      nitrogenase reactivity at low Av2/Av1 ratios, a result attributed to decreasing
      the Km for Av2-Av1 interaction. Direct reduction of bound Av2 is possibly the
      source of this kinetic enhancement. The kinetic results are considered in terms
      of the Thorneley and Lowe scheme.

PMID- 8554324
TI  - Polyethylene sulfonate: a tight-binding inhibitor of 6-phosphogluconate
      dehydrogenase of Cryptococcus neoformans.
AB  - Polyethylene sulfonate (PES) or polyvinyl sulfonate was found to be a potent
      inhibitor of a number of fungal enzymes, including 6-phosphogluconate
      dehydrogenase from Cryptococcus neoformans. The inhibition was apparently
      competitive versus either NADP or 6-phosphogluconate, with 50% inhibition at PES
      concentrations below 10 nM. Replots of slopes of double-reciprocal plots versus
      inhibitor concentration were sharply concave upward, whereas replots of slope
      versus [PES]3 were linear. The inhibition was freely reversible upon dilution of
      the enzyme-PES complex. A model is presented that involves initial binding of the
      long (M(r) 50,000) polyanionic PES at a remote site on the enzyme, followed by
      interaction of the end of the tethered polymer with the binding site for NADP or
      for 6-phosphogluconate.

PMID- 8554325
TI  - Phospholipid solubilization during detergent extraction of rhodopsin from
      photoreceptor disk membranes.
AB  - The solubilization of rhodopsin and phospholipids from disks prepared from bovine
      retinal rods was studied using five different detergents. The relative amounts of
      rhodopsin and lipid extracted during membrane solubilization differed
      dramatically with the nature of the surfactant; the two nonpolar detergents,
      Emulphogene (polyoxyethylene-10 tridecylether) and octylglucoside, removed more
      protein than lipid; two bile salt-related detergents, 3-[(3
      cholamidopropyl)dimethylammonio]-1-propane sulfonate (Chaps) and taurocholate,
      released relatively more lipid than protein; and digitonin, which shares
      characteristics with both groups of detergents, extracted more lipid per mole of
      rhodopsin than the former two but less than the latter two. Solubilization was
      temperature-dependent with all five detergents, though particularly so with
      octylglucoside: concentrations adequate for the total micellation of disks at 23
      degrees C were ineffectual at 4 degrees C. In total solubilizates of disks, the
      amount of lipid recovered in rhodopsin-lipid-detergent micelles showed a closer
      correlation with the critical micellar concentration (CMC) than with the chemical
      nature of the detergent (octylglucoside > taurocholate > Chaps > digitonin >
      Emulphogene). The higher the CMC, the larger the amount of lipid associated to
      the solubilized rhodopsin and the larger the amount of lipid reassociated to
      rhodopsin upon surfactant dilution. For all five detergents, the lipid
      progressively extracted from disks during solubilization was relatively richer in
      phosphatidylcholine (PC) than the lipid in the original membranes. The lipid
      which tended to be associated with rhodopsin in protein-lipid-detergent mixed
      micelles was also consistently richer in PC than that present in lipid-detergent
      micelles. Bleaching of solubilized rhodopsin decreased the amount of lipid in
      protein-lipid-detergent micelles. Rhodopsin photolytic transitions were faster in
      nonionic than in bile salt-related detergents.

PMID- 8554326
TI  - Extracellular domain of granulocyte-colony stimulating factor receptor.
      Interaction with its ligand and identification of a domain in close proximity of
      ligand-binding region.
AB  - An extracellular domain of human granulocyte-colony stimulating factor (G-CSF)
      receptor was expressed in and purified from Chinese hamster ovary cells. Complex
      formation between G-CSF and the receptor was studied by size exclusion
      chromatography, followed by chemical cross-linking. The receptor-ligand complex
      contained an equimolar ratio of each protein. Crosslinking experiments using
      disucciniimide suberate revealed that the native complex contained at least two
      types of cross-linked complexes; one form contained one or two G-CSF molecules
      per receptor molecule, whereas another form contained one or two G-CSF per two
      receptor molecules. The tryptic peptide map of the cross-linked complex provided
      a unique peptide peak which was not found in a peptide map of the original
      protein. Sequence analysis and mass spectrometry of the peptide indicated that
      two peptides were covalently linked by cross-linker, one peptide from G-CSF and
      the other from the receptor. In the cross-linked peptide, Lys-242 of the receptor
      cross-linked the amino terminal Met of G-CSF through the cross-linker. It was
      also shown that the N-terminal Met of G-CSF was readily acetylated in the
      receptor-ligand complex, indicating that it was not directly involved in receptor
      binding. The results show that the N-terminal Met of G-CSF is located at a
      distance of approximately 11 A from a reactive Lys-242 of the receptor in the
      ligand-receptor complex.

PMID- 8554327
TI  - Rigidity of a B-Z region incorporated into a plasmid as monitored by electron
      paramagnetic resonance.
AB  - Electron paramagnetic resonance spectroscopy was employed to monitor the dynamics
      associated with a B-Z transition in both a linear (dG-dC)n and a modified pUC8
      plasmid. A spin label consisting of cytidine substituted in position C5 with an
      11-atom-tethered 5-membered ring nitroxide (DCAVAP) was incorporated into linear
      (dG-dC)n with Micrococcus luteus DNA polymerase or into a specific 34-bp Z-DNA
      forming region of the 2.7-kb plasmid pRDZ8 with Thermus aquaticus DNA polymerase
      (Stoffel fragment). Although DCA-VAP is a modified nucleotide, it was an
      excellent substrate for both enzymes. The Z conformation was induced by changing
      the salt concentration from 0.01 to 4.5 M. The EPR line shape changed in response
      to the switch in DNA conformation. The degree of change was quantitatively
      similar for both the linear polymer and the plasmid with its Z-DNA-forming
      region. A motional analysis which focuses on local dynamics indicates that the
      order parameter S for the spin-labeled systems increases upon conversion from B
      DNA to Z-DNA. This decrease in motional freedom is consistent with the
      observation that Z-DNA is more rigid than B-DNA.

PMID- 8554328
TI  - Interaction of nitric oxide with photoexcited rose bengal: evidence for one
      electron reduction of nitric oxide to nitroxyl anion.
AB  - The interaction of nitric oxide (.NO) with Rose Bengal (RB) in the presence of
      electron donors was investigated. Upon illumination of a mixture of RB and .NO
      with visible light, an enhancement in the rate of .NO consumption was observed
      that increased with increasing RB concentration. In the presence of electron
      donors (NADH, glutathione, or ascorbate), the rates of .NO depletion increased
      further. NADH enhanced .NO depletion to a greater extent than either glutathione
      or ascorbate. Photoactivated RB under anaerobic conditions reacts with NADH to
      form the RB anion radical (RB.-), which has a characteristic visible absorption
      band centered at 418 nm. Rose Bengal anion radical disporportionates to give RB
      and a colorless reduced form of RB, RBH-. The net result of this process is the
      photobleaching of RB. The presence of .NO during irradiation of RB and NADH
      introduced a lag time into the kinetics of RB photobleaching. The length of this
      lag time was proportional to the concentration of .NO. A similar lag time, which
      was also dependent on the .NO concentration, was observed in the kinetics of
      formation of RB.-. The three-line electron spin resonance (ESR) spectrum of RB.-,
      with an intensity ratio 1:2:1, was obtained during irradiation of RB and NADH
      under anaerobic conditions. .NO introduced a concentration-dependent lag time
      into the kinetics of the appearance of this ESR signal. We propose that .NO
      oxidizes RB.- to regenerate RB and thus inhibit photobleaching until .NO is
      consumed. This reaction predicts the formation of NO-, the one-electron reduced
      form of .NO. Nitrous oxide, a characteristic dimerization product of NO-, was
      detected by gas chromatography. This evidence indicates the occurrence of a Type
      I mechanism between photoactivated RB and .NO.

PMID- 8554329
TI  - Thermodynamic analysis of the oxidative deamination of polyamines by bovine serum
      amine oxidase.
AB  - The effect of incubation temperature on the activity of bovine serum amine
      oxidase was studied using natural substrates of this enzyme, namely spermine and
      spermidine. The activity behavior was found to be rather complex and different
      from that observed using benzylamine as substrate. The enzyme is fully active
      after 3 min incubation at temperatures up to 60 degrees C, while at higher
      temperatures it shows an S-shaped irreversible decrease of the activity with a
      T50 of about 70 degrees C. The dependence of the kinetic parameters Kcat and Km
      on temperature was also studied in the range 5-66 degrees C, measuring the
      initial rates of oxidation of spermidine. The Arrhenius plot of kcat shows a
      continuous bend in the thermal stability range of the enzyme. This nonlinearity
      is due to the dramatic change of kcat activation entropy (from +11 eu at 8
      degrees C, to -31 eu at 50 degrees C) and indicates that kcat is a composite
      constant, involving two or more successive steps characterized by different
      kinetic parameters. In the case of the ratio kcat/Km, which for natural
      substrates of bovine serum amine oxidase was shown that its dependence on ionic
      strength gives information on the influence of electrostatic field on k1
      (Stevanato et al. (1994) Biochem. J. 299, 317-320), where k1 is the kinetic
      constant of interaction between the polyamine and the enzyme, the Arrhenius plot
      is linear in the range 12-45 degrees C, and an activation entropy of 18.8 eu was
      calculated at 37 degrees C. This value is in accord with a mechanism involving
      the formation of a polyamine-enzyme complex which is accompanied by
      neutralization of charges between the polycationic substrate and negatively
      charged groups of the enzyme.

PMID- 8554330
TI  - Cloning, sequence, and expression of mouse protoporphyrinogen oxidase.
AB  - Protoporphyrinogen oxidase (EC 1.3.3.4) is the penultimate enzyme in the heme
      biosynthetic pathway, catalyzing the six-electron oxidation of protoporphyrinogen
      to protoporphyrin. A dominantly inherited genetic deficiency in this enzyme
      results in the disease variegate porphyria. We now report the cloning, sequence,
      and expression of mouse protoporphyrinogen oxidase. The cDNA for mouse
      protoporphyrinogen oxidase was obtained by complementation of Escherichia coli
      SASX38, a protoporphyrinogen oxidase-deficient strain, with a mouse
      erythroleukemia (MEL) cell expression library. The sequence of this cDNA along
      with 5' untranslated sequence obtained by 5' rapid amplification of cDNA ends of
      MEL cell mRNA is 1814 bp in length and contains an open reading frame of 1431 bp.
      This encodes a protein of 477 amino acid residues with a calculated molecular
      weight of 50,870. The protein as expressed in E. coli is sensitive to inhibition
      by the diphenyl ether herbicide acifluorfen. Northern blot analyses of RNA from
      uninduced and induced MEL cells as well as mouse hepatoma cells all show two
      major mRNA species of 1.8 and 3.6 kb.

PMID- 8554331
TI  - beta-Cryptoxanthin selectively increases in human chylomicrons upon ingestion of
      tangerine concentrate rich in beta-cryptoxanthin esters.
AB  - beta-Cryptoxanthin is a major source of vitamin A, often second only to beta
      carotene, and is present in fruits such as oranges, tangerines, and papayas.
      Here, we studied the uptake of this carotenoid upon ingestion of tangerine juice
      concentrate, rich in beta-cryptoxanthin esters. Increasing amounts of free beta
      cryptoxanthin were detected in chylomicrons and serum. Peak levels in
      chylomicrons were reached at t = 6 h, and the concentration returned toward basal
      levels at t = 9 h. No beta-cryptoxanthin esters were detected in chylomicrons or
      serum, indicating efficient cleavage in the intestine before the carotenoid is
      incorporated into lipoproteins by the liver. Other xanthophyll esters, e.g., of
      zeaxanthin and lutein, were present in low amounts in the tangerine concentrate.
      As with beta-cryptoxanthin, no esters appeared in serum or chylomicrons,
      suggesting that the cleavage of carotenoid esters prior to release into the
      lymphatic circulation occurs generally in human oxocarotenoid biokinetics.

PMID- 8554332
TI  - Epitope mapping and tight-binding inhibition with monoclonal antibodies directed
      against Escherichia coli glucosamine 6-phosphate synthase.
AB  - In the present work, we attempt to identify inhibitory monoclonal antibodies
      directed against Escherichia coli glucosamine-6P synthase (GlmS) and to localize
      the corresponding epitopes to better understand the topology of the enzyme during
      catalysis. Four of the 15 monoclonal antibodies have been shown to be specific
      for the native form of the enzyme and 2 of them, 505.1 and 522.2, strongly
      inhibit the glucosamine synthase activity. Kinetic analysis of 505.1 antibody
      behavior revealed a tight-binding inhibition with a Ki = 40 +/- 20 pM, a value
      which is four orders of magnitude lower than the best active site-directed
      inhibitor reported so far. The reactivity of all the monoclonal antibodies with
      601 overlapping octapeptides covering the entire sequence of GlmS was tested by
      enzyme-linked immunosorbent assay for precise epitope mapping. Four linear
      epitopes specific for the denatured protein and one present in both native and
      denatured enzyme were defined by this approach. Neither 505.1 nor 522.2 was
      directed against linear epitopes. However, evidence for the binding of 505.1 at
      the glutamine catalytic site was shown by using site-directed mutants of GlmS as
      well as by competition experiments with an irreversible inhibitor. The mAb 105.1,
      which recognizes the octapeptide containing the sequence RWATHG conserved among
      the six glucosamine-6P synthases reported so far, allowed the detection of the
      human enzyme.

PMID- 8554333
TI  - A second molybdoprotein aldehyde dehydrogenase from Amycolatopsis methanolica
      NCIB 11946.
AB  - Methanol-grown Amycolatopsis methanolica NCIB 11946 contains a molybdoprotein
      dehydrogenase, active with aldehydes and formate esters as substrates and with
      Wurster's blue as electron acceptor, the so-called formate ester dehydrogenase
      (FEDH) (van Ophem et al., 1992, Eur. J. Biochem. 206, 519-525). It appears now
      that another molybdoprotein dehydrogenase is present in this organism. This
      enzyme, indicated here as dye-linked aldehyde dehydrogenase (DL-AlDH), has the
      same set of cofactors and converts the same type of substrates but with different
      specificity, and uses 2,6-dichlorophenol-indophenol as sole artificial electron
      acceptor for those conversions. The enzymes also differ in their quaternary
      structure, FEDH having an alpha, beta, gamma and DL-AlDH having an alpha, beta,
      gamma 2 composition. Furthermore, differences exist with respect to the sizes and
      the N-terminal amino acid sequences of their subunits, indicating that the
      enzymes derive from different genes. However, neither their substrate specificity
      nor their induction pattern give a clear indication for distinct physiological
      roles. Just like other bacterial molybdoprotein dehydrogenases, DL-AlDH consists
      of three different subunits (87, 35, and 17 kDa) and contains FAD, molybdopterin
      cytosine-dinucleotide cofactor, Fe, and acid-labile sulfide in a molar ratio of
      1:1:4:4. Although eukaryotic xanthine oxidase and dehydrogenase differ from these
      prokaryotic dehydrogenases in size and number of their subunits, certain
      stretches of amino acid sequences show similarity and the magnetic coupling
      between the Mo and the [2Fe-2S]-1 cluster in DL-AlDH and bovine milk xanthine
      oxidase is of the same magnitude. In view of this similarity, the topology of the
      cofactors in the active site of this type of molybdoproteins might be conserved
      among enzymes from prokaryotic as well as eukaryotic organisms.

PMID- 8554334
TI  - Thyromimetic action of the peroxisome proliferators clofibrate, perfluorooctanoic
      acid, and acetylsalicylic acid includes changes in mRNA levels for certain genes
      involved in mitochondrial biogenesis.
AB  - The effects of three peroxisome proliferators on the mRNA levels for some
      mitochondrial inner-membrane proteins in rat liver were investigated. Clofibrate,
      perfluorooctanoic acid, and acetylsalicylic acid all increased the mRNA levels
      for the mitochondrial-encoded respiratory-chain components cytochrome c oxidase
      subunit I and NADH dehydrogenase subunit I. Mitochondrial 16S rRNA was also
      induced by clofibrate. The mRNA levels for the nuclear-encoded mitochondrial
      inner-membrane proteins adenine nucleotide translocator and cytochrome c1 were
      selectively induced by the different peroxisome proliferators. Malic enzyme,
      which is induced by thyroid hormone, was also induced by the three peroxisome
      proliferators tested. These effects are in some ways similar to those obtained
      with thyroid hormone.

PMID- 8554335
TI  - Endoplasmic reticulum kifunensine-resistant alpha-mannosidase is enzymatically
      and immunologically related to the cytosolic alpha-mannosidase.
AB  - Studies were undertaken to evaluate the relationship of the recently described
      (S. Weng and R. G. Spiro, 1993, J. Biol. chem. 268, 25656-25663) rat liver
      kifunensine (KIF)-resistant mannosidase (ER mannosidase II) to the mannose
      trimming enzyme of cytosol. We observed that the ER mannosidase II manifests a
      large number of catalytic and immunological properties similar to those of the
      cytosolic alpha-mannosidase, which contrast with the quite different
      characteristics of the KIF-sensitive enzyme (ER mannosidase I). In addition to a
      mutual resistance to KIF inhibition, the cytosolic enzyme and ER mannosidase II
      have comparable susceptibility to blocking by swainsonine and 1,4-dideoxy-1,4
      imino-D-mannitol, and the latter agent was found to function effectively both in
      vitro and in vivo. The cytosolic and ER II mannosidases were alike in
      specifically excising the terminal mannose of the alpha 1,6-linked chain of
      Man9GlcNAc to yield Man8GlcNAc isomer C; in preferentially hydrolyzing
      polymannose-GlcNAc1 over polymannose-GlcNAc2 substrates; and in cleaving p
      nitrophenyl alpha-D-mannoside. An immunological cross-reactivity between
      cytosolic mannosidase (M(r) 105 kDa) and ER mannosidase II (M(r) 82 kDa), neither
      of which is N-glycosylated, was established, suggesting that the latter is
      translocated posttranslationally into the lumen of the ER compartment in which we
      found it to be present as a soluble protein. Since antibodies directed against a
      sequence near the C-terminal end of the cytosolic enzyme reacted with ER
      mannosidase II while those against a sequence close to the N-terminus did not, it
      is likely that a proteolytic cleavage of the latter segment takes place during or
      after translocation. The absence in ER mannosidase II of the pronounced cobalt
      activation of the cytosolic enzyme suggests that the portion of the polypeptide
      chain removed during the 105- to 82-kDa conversion includes the binding domain
      for this ion.

PMID- 8554336
TI  - Multiple forms of selenoprotein P in rat plasma.
AB  - SDS-PAGE of immunoaffinity-purified rat seleno-protein P demonstrates a major
      band at 57 kDa and a less intense band at 45 kDa, suggesting the existence of
      more than one form of the protein. Separate experiments were carried out in which
      plasma from rats administered 75Se and immunoaffinity-purified 75Se-labeled
      selenoprotein P were applied to a heparin-Sepharose column at pH 7. In each
      experiment three peaks of 75Se-labeled protein were eluted during a continuous
      gradient from pH 7 to pH 8.5. The remaining 75Se-labeled material was eluted as a
      single peak by 1 M NaCl. Phosphorimaging of the SDS-PAGE gel of the peaks
      revealed that the first peak (1a) contained two bands (45 and 57 kDa) while the
      three remaining peaks each contained one band (peak 1b, 45 kDa and peaks 2 and 3,
      57 kDa). N-terminal sequencing of the first eight amino acids of each band
      revealed that all five have the same N-terminal amino acid sequence and therefore
      are forms of selenoprotein P. Staining using a digoxigenin-based staining
      procedure revealed that all five forms contain carbohydrate. This demonstrates
      that plasma-derived selenoprotein P can be separated into five forms based on SDS
      PAGE migration and heparin-Sepharose affinity and that at least two isoforms of
      selenoprotein P exist based on the presence of 45- and 57-kDa forms. The five
      forms have been given designations based on their order of elution from the
      heparin-Sepharose column and their M(r) on SDS-PAGE: selenoprotein P57A (peak 1a,
      57 kDa), selenoprotein P45A (peak 1a, 45 kDa), selenoprotein P45B (peak 1b, 45
      kDa), selenoprotein P57B (peak 2, 57 kDa), and selenoprotein P57C (peak 3, 57
      kDa).

PMID- 8554337
TI  - Alterations of heparan sulfate moieties in cultured endothelial cells exposed to
      endotoxin.
AB  - In previous studies, we observed that exposure to endotoxin markedly reduces the
      level of heparan sulfate proteoglycans in the extracellular matrix of cultured
      endothelial cells and at the same time causes the accumulation of proteoglycans
      bearing glycosaminoglycan chains of reduced size in the conditioned medium (P.
      Colburn, E. Kobayashi, and V. Buonassisi, 1994, J. Cell. Physiol. 159, 121-130).
      We have now investigated the structural and ligand-binding features which
      distinguish the matrix glycosaminoglycan moiety and the nature of the alterations
      of the truncated glycosaminoglycans. The matrix glycosaminoglycans are less
      sulfated than those of other cellular compartments and are more extensively
      degraded by heparitinase I, yielding a larger proportion of smaller
      oligosaccharides. In the binding assays, matrix glycosaminoglycans had greater
      specificity than those of the cell surface for a synthetic peptide patterned on
      the carboxyl-terminal sequence of an N-glycan sulfated protein synthesized by the
      endothelial cell. The nature of the alteration caused by exposure to endotoxin
      consists in the loss of a region rich in sulfate, located at the nonreducing end
      of the glycosaminoglycan chain. We also determined that only proteoglycans with
      intact chains are found in the extracellular matrix of endotoxin-treated cells.

PMID- 8554338
TI  - Identification of the molybdenum cofactor of dimethyl sulfoxide reductase from
      Rhodobacter sphaeroides f. sp. denitrificans as bis(molybdopterin guanine
      dinucleotide)molybdenum.
AB  - Chemical analysis of dimethyl sulfoxide reductase from Rhodobacter sphaeroides f.
      sp. denitrificans has shown that its molybdenum center contains two molybdopterin
      guanine dinucleotide molecules and a single atom of molybdenum. The enzyme, which
      exists as a monomer of 86 kDa, was shown to contain 1 mol of molybdenum, 4 mol of
      organic phosphate, and 2 mol of guanine per mole of protein. In addition, the
      relative yield of Form A, a fluorescent derivative of molybdopterin, was twice
      that obtained from sulfite oxidase, a protein which contains a single
      molybdopterin per molybdenum. These findings correlate with the recent report of
      the presence of two molybdopterin ligands in the tungsten cofactor of aldehyde
      ferredoxin oxidoreductase from Pyrococcus furiosus, providing the first example
      of a bis(pterin)molybdenum cofactor and extending this structural motif to the
      molybdopterin dinucleotide enzymes.

PMID- 8554339
TI  - Superoxide scavenging by Mn(II/III) tetrakis (1-methyl-4-pyridyl) porphyrin in
      mammalian cells.
AB  - The superoxide dismutase mimic Mn(II/III) tetrakis (1-methyl-4-pyridyl) porphyrin
      (Mn(II/III)TMPyP) was examined for its superoxide radical (O2.-)-scavenging
      ability in cultured mammalian cells. Mn(III)TMPyP (< 5 microM) added to culture
      media relieved growth inhibition and decreased the inactivation of the O2(.-)
      sensitive enzyme aconitase in cells exposed to the O2(.-)-generating phenazine
      pyocyanine. Treatment of cells with Mn(III)TMPyP did not measurably affect
      cellular O2.- production as revealed by rates of cyanide-resistant respiration
      with or without added pyocyanine. In contrast, Mn(II/III)TMPyP enhanced O2.-
      production in cells when the redox-active naphthoquinone menadione was present as
      measured by both increased cyanide-resistant respiration rates and aconitase
      inactivation. In vitro, Mn(II/III)TMPyP catalyzed the oxidation of ascorbate, and
      menadione enhanced this effect. Mn(III)TMPyP did not protect aconitase when O2.-
      production was elicited in mitochondria by antimycin A and the uncoupler carbonyl
      cyanide p-trifluoromethoxyphenylhydrazone. The results support a reductant-O2.
      :oxidoreductase mechanism for O2.- scavenging by Mn(II/III)TMPyP in the mammalian
      cytosol as proposed for its action in Escherichia coli, but also indicate that
      Mn(II/III)TMPyP can either scavenge or produce O2.- in cells depending upon the
      prevailing pathways of Mn(II/III)TMPyP oxidation-reduction.

PMID- 8554340
TI  - Successive elution by ion-exchange chromatography of H3-H4 histone complexes
      differing in their degree of acetylation.
AB  - On Biorex 70 ion exchanger at neutral pH the histones H3 and H4 are usually
      eluted by 4 M guanidinium chloride (gdm Cl). In order to protect cysteines and
      methionines from oxidation we systematically added 2-mercaptoethanol to the
      elution buffer. This resulted in the two histones being unexpectedly eluted
      together at around 1 M gdm Cl. The use of a shallower gradient resulted in a
      division in the peak of histones, with the acetylated species of H3 and H4 being
      eluted first and the nonacetylated species of H3 and H4 eluted last. When histone
      H3 or histone H4 was applied alone or when the chromatography was performed at
      low pH, these histones were eluted in the usual position at about 4 M gdm Cl.
      These events mean that the simultaneous elution of the histones H3 and H4 at
      about 1 M gdm Cl involves the formation of H3-H4 complexes. Therefore, the H3-H4
      complex may be obtained by ion-exchange chromatography as the H2A-H2B complex was
      previously; furthermore, the former was fractionated according to postsynthetic
      modifications. This finding provides a new basis for explaining some of the
      previous elution profiles of chromatin extracts.

PMID- 8554341
TI  - Spermine binding to GC-rich DNA: experimental and theoretical studies.
AB  - The DNA binding of spermine has been studied using experimental and computational
      approaches. Spermine blocks 5'-GC interstrand crosslinking by 2,5
      diaziridinylbenzoquinone in the oligonucleotide duplex 5'-CTTCCAAGATGCATCAGATG 5'
      CATCTGATGCATCTTGGAAG (where the underlined nucleotide bases represent the
      crosslinking site). Molecular dynamics simulations suggest that this is a result
      of preferential spermine binding at the 5'-GC major groove site of the
      oligonucleotide. A further simulation with a GC-alternating sequence shows a
      similar preference for the 5'-GC step. In a simulation including multiple
      spermine molecules, occupation of alternate 5'-GC steps occurred. From this, we
      deduced a mechanism for the experimentally observed cooperativity of spermine
      binding to poly(dGdC)2.

PMID- 8554342
TI  - Plasma membrane is the primary site of localization of the nonactivated estrogen
      receptor in the goat uterus: hormone binding causes receptor internalization.
AB  - Evidence is presented to show that the cellular site of localization of the goat
      uterine nonactivated estrogen receptor (naER) is the plasma membrane. Exposure of
      purified plasma membrane preparations to estradiol (20 nM) causes dissociation of
      the receptor from the membrane into the medium. This receptor movement takes
      place in the presence of diethylstilbestrol while testosterone, progesterone,
      dexamethasone, and tamoxifen do not facilitate the dissociation of the naER from
      the plasma membrane. Further, tamoxifen inhibits the estradiol-mediated
      dissociation of the naER from the plasma membrane. The naER is a glycoprotein and
      is also a tyrosine kinase. The tyrosine kinase activity is inhibited in the
      presence of estrogens while tamoxifen reverses this estrogen-dependent
      inhibition.

PMID- 8554343
TI  - Thermal stability of horse spleen apoferritin and human recombinant H
      apoferritin.
AB  - The thermal stability of horse spleen apoferritin, a heteropolymer composed of
      90% L and 10% H chains, has been studied by differential scanning calorimetry and
      compared with that of the human recombinant H homopolymer. The denaturation
      temperatures (Tm) are significantly higher for the horse spleen polymer than for
      the recombinant protein under all experimental conditions (e.g., at pH 7, Tm
      values are > or = 93 and 77 degrees C, respectively). The thermal denaturation
      process displays substantial reversibility for both polymers up to a few degrees
      below Tm, as indicated by CD measurements in the far and near uv regions. At
      temperatures higher than Tm the thermograms are influenced by the exothermic
      contribution of aggregation and/or precipitation. The H homopolymer thermogram,
      which is not distorted by the exotherm, is consistent with a multistate
      denaturation process. Acid dissociation of apoferritin produces stable dimeric
      subunits. The thermal unfolding of both dimeric subunits is reversible at least
      up to Tm and is characterized by an inversion of stability relative to the
      polymers (at pH 3.5, Tm is 42 degrees C for the horse spleen and 50 degrees C for
      the H subunit). These results indicate that the stabilization of the polymeric
      structure arises mainly from interactions between dimers, in accordance with the
      crystallographic evidence that the dimers are the building blocks of the
      polymeric molecule.

PMID- 8554344
TI  - Detection of free radicals produced from reactions of lipid hydroperoxide model
      compounds with Cu(II) complexes by ESR spectroscopy.
AB  - Using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap, alkoxyl radicals
      and peroxyl radicals produced from the reactions of tert-butyl
      hydroperoxide(tBuOOH) and cumene hydroperoxide (PhC(CH3)2OOH) with some
      copper(Cu)(II) complexes such as Cu(II) complexes of cimetidine (Cim), cyclo(L
      histidyl-L-histidyl) (CyHH), L-histidylglycine (HG), and L-histidylglycylglycine
      (HGG) were detected by electron spin resonance (ESR) spectroscopy. However,
      Cu(II) complexes of glycyl-L-histidine (GH), glycyl-L-histidylglycine
      (GHG),glycylglycyl-L-histidine (GGH), and glycylglycyl-L-histidyl-glycine (GGHG)
      did not cause the generation of free radicals during the reaction with tert-butyl
      or cumene hydroperoxide. Addition of a biological reductant such as cysteine or
      glutathione to the system including these Cu(II) complexes and hydroperoxides
      gave tert-butoxyl and cumyl alkoxyl (RO.) radicals, respectively. These alkoxyl
      radicals underwent subsequent beta-scission reaction and generated the carbon
      centered radical (R.). Although cysteine and glutathione are considered to be
      cellular antioxidants, our results suggest that these biological reductants
      facilitate Cu(II) complexes-dependent free radical generation.

PMID- 8554345
TI  - Differential effects of bovine PA28 on six peptidase activities of the lobster
      muscle proteasome (multicatalytic proteinase).
AB  - PA28, an endogenous activator of the bovine proteasome, stimulated the branched
      chain amino acid-preferring (BrAAP; 99-fold activation), small-neutral amino acid
      preferring (11-fold), acidic chymotrypsin-like (26-fold), and peptidylglutamyl
      peptide hydrolase (14-fold) activities of the lobster muscle proteasome, while
      having little or no effect on the trypsin-like, neutral chymotrypsin-like, and
      caseinolytic activities. These results show that the BrAAP activity, which has
      been linked to the degradation of myofibrillar proteins by the heat-activated
      proteasome, is allosterically regulated. However, the activation by PA28 differs
      from that induced by heat treatment, since heat activation stimulated both the
      BrAAP and the proteolytic activities but not the other peptidase activities. PA28
      shifted the pH optimum of the acidic chymotrypsin-like activity from pH 6-6.5 to
      pH 7-7.5, while stimulating the activity about 10-fold. These results suggest
      that PA28 is involved in the activation of the acidic chymotrypsin-like component
      at physiological pH.

PMID- 8554346
TI  - Expression of biologically active human SPARC in Escherichia coli.
AB  - Human SPARC has been cloned by the polymerase chain reaction from an endothelial
      cell cDNA library and expressed in Escherichia coli as a biologically active
      protein. Transcriptional expression of the insert cDNA was dependent on the
      activation of the T7 RNA polymerase promoter by isopropylgalactopyranoside. Two
      forms of recombinant SPARC (rSPARC) protein were recovered from BL21 (DE3) E.
      coli after transformation with the plasmid pSPARCwt: a soluble, monomeric form of
      rSPARC and an insoluble, aggregated form sequestered in inclusion bodies. The
      isolation of the soluble form of rSPARC was accomplished by anion-exchange,
      nickel-chelate affinity, and gel filtration chromatographies. The isolated
      protein was an intact, full-length polypeptide of 293 amino acids by the
      following criteria: N-terminal amino acid sequence, reaction with anti-SPARC
      immunoglobulins specific for N-terminal and C-terminal sequences, and interaction
      of the C-terminal histidine tag of rSPARC with a nickel-chelate affinity resin.
      Circular dichroism and intrinsic fluorescence spectroscopy indicated that the
      conformation of rSPARC was dependent on interaction with Ca2- ions. The
      recombinant protein inhibited cell spreading and bound specifically to bovine
      aortic endothelial cells. Levels of bacterial endotoxin (< 18 pg/microgram
      rSPARC) present in rSPARC preparations were below the threshold that affects the
      behavior of these endothelial cells. These conformational and biological
      properties of rSPARC are consistent with previously described characteristics of
      the native protein. The purification of biologically active rSPARC, as well as
      mutated forms of the protein, will provide sufficient quantities of protein for
      the determination of structure/function relationships.

PMID- 8554347
TI  - Affinity chromatography of regulatory subunits of protein phosphatase-1.
AB  - In this study we demonstrate that recombinant rabbit muscle protein phosphatase-1
      immobilized on CH-Sepharose is an efficient affinity chromatography support for
      the isolation of subunits of phosphatase-1. The support was used to isolate the
      glycogen binding subunit of phosphatase-1 from muscle and nonmuscle rat tissues.
      Examination of the affinity-purified material from rat heart and liver showed
      that the major component was a 160-kDa polypeptide on SDS-PAGE. The identity of
      the purified liver 160-kDa polypeptide as the glycogen binding subunit was
      confirmed by the demonstration that it is capable of binding to glycogen, and is
      phosphorylated by the catalytic subunit of PKA. The novel observation was made
      that the phosphorylation was dependent on the presence of glycogen. Examination
      of the material from heart, lung, liver, kidney, and brain showed a similar
      phenomenon. Our studies show that this subunit is widely distributed in tissues.
      The affinity support was also efficient in the isolation of the NIPP-1 (nuclear
      inhibitor of protein phosphatase-1) proteins from calf thymus. Examination of
      heat-treated extracts of rat liver led to the isolation of a novel 19-kDa
      inhibitory protein which could also be phosphorylated by PKA and may represent
      the rat liver homolog of calf thymus NIPP-1.

PMID- 8554348
TI  - Correlation between glutathione and stimulation of the pentose phosphate cycle in
      situ in Chinese hamster ovary cells exposed to hydrogen peroxide.
AB  - The effect of glutathione on stimulation of pentose phosphate cycle activity
      during oxidative challenge was evaluated in intact Chinese hamster ovary cells in
      situ. Glutathione was depleted to varying levels with L-buthionine-[S,R]
      sulfoximine. The level of stimulation of pentose phosphate cycle activity by
      exogenous H2O2 (4 mumol/10(7) cells) was dependent on the time of pretreatment
      with L-buthionine-[S,R] sulfoximine and was proportional to the total glutathione
      concentration. This was not related to the amount of GSSG, since its level was
      exceedingly low under conditions where H2O2 stimulated pentose phosphate cycle
      activity. The amount of GSSG in cells increased after exposure to 10-fold higher
      concentrations of H2O2 under conditions where there was no stimulation of pentose
      phosphate cycle activity above the basal level. Paraquat caused stimulation of
      pentose phosphate cycle activity which was independent of L-buthionine-[S,R]
      sulfoximine pretreatment and of the glutathione content of cells. The stimulatory
      effects of both oxidants on pentose phosphate cycle activity appeared to be
      independent of glutathione reductase activity since they were unaffected in cells
      treated with 1,3-bis(2-chloroethyl)-1-nitrosourea. The inhibitory effect of L
      buthionine-[S,R] sulfoximine on stimulation of pentose phosphate cycle activity
      by H2O2 did not appear to be due to the inhibitor itself, but rather to the
      overall level of glutathione. Glutathione could have a role in maintaining
      activity of the pentose phosphate cycle at a level which is appropriate for the
      severity of the oxidative challenge as well as for the capacity of the cellular
      antioxidant defenses.

PMID- 8554349
TI  - Characterization of the FAD binding domain of cytochrome P450 reductase.
AB  - The redox potentials of FAD and FMN of Cytochrome P450 reductase (reductase) are
      equivalent in solution but differ by 138 mV when bound to reductase. The
      interaction of each flavin with its flavin binding domain confers the unique
      electron transferring abilities to each flavin. In order to determine flavin
      binding properties and activity of the FAD binding domain, we have expressed in
      pTrcHis three fragments (1161, 1244, and 1556 bp) of rat liver reductase cDNA
      encompassing the proposed FAD and NADPH binding domain. The FAD binding fragments
      from cells harboring the 1161- and 1556-bp-containing vectors were stable and
      bound 0.66 and 0.71 mol FAD/mol enzyme, respectively. Both fragments reduce
      ferricyanide (54 and 104% of FMN-less reductase/mol bound flavin, respectively)
      and participate in the transhydrogenation reaction of 3-AcPy-ADP (41 and 65% of
      FMN-less reductase/mol bound flavin, respectively). FAD-less fragments were
      purified and reconstituted with 8-amino-FAD and 8-chloro-FAD to determine binding
      efficiencies.

PMID- 8554350
TI  - Treatment of arrhythmias by radiofrequency ablation.

PMID- 8554351
TI  - Irradiation in the prevention of transfusion associated graft-versus-host
      disease.

PMID- 8554352
TI  - Acellular pertussis vaccines.

PMID- 8554353
TI  - Plasma cholesterol and other cardiac risk factors in adolescent girls.
AB  - The aim was to examine the effects of smoking, physical activity, and body mass
      on total cholesterol and high density lipoprotein cholesterol (HDL-C) in
      adolescent schoolgirls in Sydney, Australia. Body mass index (BMI) and waist to
      hip ratio (WHR) were determined in 144 girls aged 15 to 18 years. Total
      cholesterol (TC) and HDL-C were estimated on fingerprick blood and behavioural
      variables assessed by questionnaire. Prevalence of overweight (> 90th centile for
      BMI) was less in Australian adolescents than reported from the USA. Smokers had
      lower total cholesterol than non-smokers; this was partly explained by a lower
      HDL-C in the smokers. Physical activity was associated with a less atherogenic
      TC/HDL-C ratio. Girls with BMI > 90th centile had higher mean TC/HDL-C and
      apoprotein B than the group as a whole but those > 90th centile for WHR did not.

PMID- 8554354
TI  - Diet, obesity, and metabolic control in girls with insulin dependent diabetes
      mellitus.
AB  - OBJECTIVE: To investigate whether girls with insulin dependent diabetes mellitus
      (IDDM) were more overweight than nondiabetic girls, and how diet, insulin
      treatment, metabolic control, age, and pubertal status were related to body
      weight and fat content. DESIGN: Case-control study. SUBJECTS AND METHODS: 48 IDDM
      girls aged 10-19 years and controls matched for age and social class participated
      in the study. Overweight was assessed by body mass index (BMI), relative weight,
      and body fat from skinfold thicknesses. Food consumption data were collected by a
      48 hour recall method. RESULTS: The girls with IDDM were more overweight than
      control girls according to all measures of obesity (for example, mean BMI 20.3 v
      18.9 kg/m2). The daily insulin dose/body weight correlated positively with BMI
      and per cent body fat. CONCLUSIONS: Girls with IDDM are more overweight than
      their peers, which indicates that a more effective prevention of obesity is
      needed in the treatment of diabetes.

PMID- 8554355
TI  - Persistent nocturnal cough in childhood: a population based study.
AB  - A cross sectional epidemiological study was carried out to investigate the
      validity of persistent nocturnal cough (PNC) as an independent marker of
      childhood asthma. A screening questionnaire on respiratory symptoms was applied
      to 4003 children attending primary schools in Aberdeen, after which 799
      symptomatic children and a random selection of 229 asymptomatic children were
      invited to attend for a diagnostic interview. Six hundred and seven (359 boys and
      248 girls) symptomatic children and 135 asymptomatic children (57 boys and 78
      girls) were selected from the screening questionnaires. Of 607 children with
      respiratory symptoms when interviewed, 27 (nine boys and 18 girls) had isolated
      PNC, and 97 (51 boys and 46 girls) had multiple symptoms (polysymptomatic
      asthma). The incidence of prematurity was highest in the group with PNC (19%).
      The prevalence of hay fever in children with PNC (11%) was similar to that of the
      asymptomatic group (15%) and less than that in the group with polysymptomatic
      asthma (41%). Eczema was twice as common in the PNC (19%) as in the asymptomatic
      children (10%) but only half as common in the polysymptomatic asthma group (35%).
      The prevalence of a parental history of hay fever was similar in all three
      groups. The prevalence of a parental history of eczema was similar in the PNC
      (7%) and asymptomatic (7%) groups but higher in the polysymptomatic asthma group
      (22%). The prevalence of a history of parental asthma was 30% in children with
      PNC, 13% in the asymptomatic group, and 42% in those with polysymptomatic asthma.
      The parents of three (11%) children with PNC were aware of a diagnosis of asthma;
      two of these children (7%) were on inhaled bronchodilator treatment and one (4%)
      was on a slow release theophylline preparation. Using a stepwise discriminant
      analysis procedure, in 18 (67%) children with PNC predicted membership was in the
      asymptomatic group and only nine (33%) children with PNC were grouped into the
      polysymptomatic asthma category. It is concluded that the clinical features of
      children with PNC resembled those of the asymptomatic population more closely
      than those of the polysymptomatic asthmatic population. In this age group PNC, in
      the absence of wheeze, shortness of breath or tightness in the chest, is likely
      to be a manifestation of atypical or hidden asthma in only a minority of cases.

PMID- 8554356
TI  - Indoor environmental risk factors in young asthmatics: a case-control study.
AB  - One hundred and ninety three children with asthma and 318 controls aged 1-4 years
      were evaluated for atopic heredity and exposure to possible indoor risk factors
      for asthma-for example exposure to furred pets, tobacco smoke, and home dampness.
      A subgroup of cases were classified as cat and/or dog allergic on the basis of
      skin prick tests. Heredity for asthma was a significant risk factor (odds ratio
      (OR) 3.0, confidence interval (CI) 2.1 to 4.6). Environmental tobacco smoke was
      associated with an excess risk for asthma (OR 1.7, CI 1.1 to 2.3) and signs of
      home dampness tended to increase this risk (OR 1.3, CI 0.9 to 2.0). High dose
      exposure to cat and/or dog resulted in an increased risk only in asthma cases
      sensitised to cat and/or dog (OR 2.7, CI 1.0 to 7.3). A combination of high dose
      exposure to cat and/or dog, environmental tobacco smoke and damp housing was
      associated with an OR of 8.0 (CI 1.9 to 34.1). Raised indoor humidity has been
      shown to reflect low air exchange, which may also lead to increased doses of
      inhaled aeroallergens and tobacco smoke, and contribute to the interaction
      between the three risk factors.

PMID- 8554357
TI  - Clinical value of monitoring eosinophil activity in asthma.
AB  - To evaluate the use of eosinophil cationic protein (ECP) in monitoring disease
      activity in childhood asthma, serum ECP in 175 asthmatic children was assessed.
      Forty five patients with cystic fibrosis, 23 with lower respiratory tract
      infections (LRTI), and 87 healthy children were used as controls. Serum ECP
      concentrations (34.3 micrograms/l v 9.8 micrograms/l) were significantly higher
      in children with bronchial asthma than in healthy control subjects. In
      symptomatic patients with asthma serum ECP concentrations were increased compared
      with those from asymptomatic patients (40.2 micrograms/l v 14.4 micrograms/l),
      irrespective of treatment modalities (that is steroids, beta 2 agonists, or
      sodium cromoglycate). Moreover, atopy and infection appeared to be factors
      enhancing eosinophil activity in bronchial asthma as measured by serum ECP (58.4
      micrograms/l v 36.8 micrograms/l and 68.8 micrograms/l v 42.2 micrograms/l,
      respectively). In a longitudinal trial, antiasthmatic treatment modalities (that
      is steroids) reduced serum ECP within four weeks (42.2 micrograms/l v 19.0
      micrograms/l). In conclusion, the data indicate that (1) eosinophils also play a
      central part in childhood asthma; (2) serum concentrations of ECP in children
      with bronchial asthma are related to the disease severity and may thus be used
      for monitoring inflammation in childhood asthma; (3) eosinophil activity appears
      to be enhanced by atopy and infection; and (4) longitudinal measurements of serum
      ECP concentrations may be useful for optimising anti-inflammatory treatment in
      children with bronchial asthma.

PMID- 8554358
TI  - Bronchial responsiveness, eosinophilia, and short term exposure to air pollution.
AB  - The number of capillary blood eosinophils and the prevalence of bronchial
      hyperresponsiveness (BHR) were compared between schoolchildren living in a
      polluted area (Ardal) and unpolluted area (Laerdal). In Ardal there is an
      aluminium smelter emitting sulphur dioxide and fluoride to the environment. Daily
      measurements of these pollutants in ambient air were available. The mean number
      of eosinophils in Ardal was 220 x 10(6)/l compared with 106 x 10(6)/l in Laerdal.
      The prevalence of BHR was 15.9% in Ardal and 11.8% in Laerdal. The odds ratio of
      having BHR in relation to these pollutants during the last 24 hours were: 1.12
      (95% confidence interval (CI) 1.01 to 1.24) by increasing sulphur dioxide with 10
      micrograms/m3, and 1.31 (95% CI 1.07 to 1.60) when fluoride exposure increased
      with 1 micrograms/m3. Similarly, these exposures were associated with a decrease
      in eosinophils of -21 x 10(6)/l (95% CI -36 to -6) and -52 x 10(6)/l (95% CI -98
      to -8), respectively, in atopics. It is hypothesised that recent exposure to
      irritants induces changes in the airways leading to BHR in addition to
      recruitment of eosinophils to the airways in atopic subjects.

PMID- 8554359
TI  - Airway reactivity in parents of infants and young children with recurrent wheeze:
      a case-control study.
AB  - Increased airway reactivity has been found in family members of school age
      children and adults with asthma. As the relation between recurrent wheeze in
      infancy and bronchial reactivity is not yet clear, it was decided to test
      bronchial reactivity to methacholine in both parents of 50 preschool age children
      with recurrent wheeze and in 200 population based controls matched for sex, age,
      smoking habits, and atopy. Wheezy children fulfilled the following criteria:
      first attack of wheezing before the age of 2 years, at least four wheezing
      episodes triggered by a respiratory infection, negative skin prick tests, and no
      symptoms related to allergy. Four parents and five controls did not undergo the
      methacholine challenge because their forced expiratory volume in one second was <
      80% of the predicted value. Methacholine reactivity was not significantly
      different in parents and controls. In summary, an increased bronchial
      responsiveness was not found in parents of infants and young children with
      recurrent wheeze triggered by infection.

PMID- 8554360
TI  - Nebulised amiloride in respiratory exacerbations of cystic fibrosis: a randomised
      controlled trial.
AB  - OBJECTIVE: To assess the benefit of nebulised amiloride added to the standard
      inpatient treatment of a respiratory exacerbation in cystic fibrosis. DESIGN:
      Prospective, randomised, double blind, placebo controlled trial. SUBJECTS: 27
      cystic fibrosis patients (mean age 12.8 years). SETTING: Two hospitals in Leeds,
      UK. RESULTS: Both forced expiratory volume in one second (FEV1) and forced vital
      capacity (FVC) showed improvements over the course of treatment, although there
      was no difference in respiratory function between the two groups at any of three
      time periods during the study. The time to reach peak FVC was significantly
      reduced in the amiloride group (4.2 v 7.6 days; 95% CI 0.4 to 6.4 days), but not
      in the time to reach peak FEV1 (5.7 v 7.9 days; 95% CI -1.2 to 5.6 days).
      CONCLUSIONS: Amiloride did not result in a greater overall improvement in
      respiratory function. There was a suggestion that it may have an effect on the
      rate of improvement, and thus may possibly influence the duration of treatment.
      This hypothesis deserves further evaluation.

PMID- 8554361
TI  - Severe microcephaly with normal intellectual development: the Nijmegen breakage
      syndrome.
AB  - A brother and sister are described with severe microcephaly of prenatal onset,
      normal intellectual and motor development, chromosomal breakage and cellular
      immunodeficiency, which is characteristic of the autosomal recessive condition,
      Nijmegen breakage syndrome. The proband was a girl who presented at 15 months,
      with normal developmental milestones and an extremely small head circumference of
      36 cm. Twenty per cent of her lymphocytes showed spontaneous translocations
      involving chromosome 7p13, 7q35, 14q11, and 14q32. The lymphocytes also showed
      excessive x ray induced chromosome damage. She had T cell lymphopenia, but normal
      immunoglobulins, and a normal alpha fetoprotein. A brother was born shortly after
      her diagnosis was made. He also had extreme microcephaly of 28 cm, with similar
      spontaneous and x ray induced chromosomal breakage, and T cell lymphopenia.
      Neither child has clinical evidence of immunodeficiency. To test the hypothesis
      that Nijmegen breakage syndrome and ataxia telangiectasia are allelic disorders,
      haplotype analysis was carried out in the family using DNA markers spanning the
      AT locus on chromosome 11q22. The affected boy had a different haplotype from his
      affected sister. Thus in this family, the Nijmegen breakage syndrome is not
      allelic to the ataxia telangiectasia locus on chromosome 11q, and the two
      conditions are genetically distinct. The normal intellect in these children
      raises questions about normal brain development in the presence of severe
      microcephaly.

PMID- 8554362
TI  - Putting it on tape: audio taped assessment summaries for parents.
AB  - OBJECTIVE: To assess the benefits of giving parents tape recorded child
      development centre assessment report summaries. DESIGN: Prospective randomly
      allocated study. SETTING: Child development centre, Birmingham Children's
      Hospital. SUBJECTS: Parents of 113 consecutive children attending for
      multidisciplinary developmental assessment. OUTCOME MEASURES: Recall of
      information and use of, and views on, the written and tape recorded summaries.
      RESULTS: Parents who received the tape recording showed no increase in recall of
      the summary's content six weeks later. Forty three per cent of English speaking
      parents favoured the tape recorded summary, as did 89% of Urdu/Punjabi speaking
      parents. CONCLUSIONS: Tape recorded summaries were popular with parents, but
      other methods are needed to help parents, especially those whose first language
      is not English, to understand the implications of multidisciplinary assessment of
      their child.

PMID- 8554363
TI  - Differentiation of cows' milk intolerance and gastro-oesophageal reflux.
AB  - The aim of this study was to compare a non-invasive test of small bowel
      permeability with a more invasive approach involving endoscopy, mucosal biopsy,
      and oesophageal pH monitoring for rapidly differentiating gastro-oesophageal
      reflux (GOR) and cows' milk intolerance in 25 infants with persistent vomiting.
      Each subject underwent a cellobiose/mannitol permeability study, upper
      gastrointestinal endoscopy with oesophageal and small bowel biopsies, and a 24
      hour pH study. Reflux disease and/or cows' milk intolerance was responsible for
      vomiting in 24 (96%) of the subjects. Sixteen (64%) of the infants had GOR alone,
      four (16%) had GOR and cows' milk intolerance, and four (16%) had cows' milk
      intolerance alone. Morphometric analysis of small bowel biopsies was abnormal in
      19% of the patients with GOR alone and in 67% with cows' milk intolerance with or
      without GOR. The permeability test was abnormal in only 6% of the patients with
      GOR but in 100% with GOR and cows' milk intolerance and in 100% with cows' milk
      intolerance alone. The non-invasive permeability study aimed at rapid
      determination of cows' milk intolerance should pre-empt a more invasive approach
      in the evaluation of infants with persistent vomiting.

PMID- 8554364
TI  - Factors affecting rectal temperature in infancy.
AB  - The recordings of 1197 overnight rectal temperatures from infants of up to 24
      weeks of age have been analysed with respect to 12 variables, including a number
      of risk factors for sudden infant death syndrome. Multivariable regression was
      used to identify if parental smoking, bottle feeding, sleeping position, and
      birth weight affect the overnight rectal temperature of infants. The rectal
      temperature, averaged over the period from three to five hours after the infants
      were put to bed, correlated well (R = 0.36) with the collected variables. An
      increase in the infant's age, birth weight, and the supine sleeping position all
      decreased the night time rectal temperatures. However, an increase in the night
      time room temperature, weight, and the combination of bottle feeding and parental
      smoking produced an increase in rectal temperature. The individual effects of
      bottle feeding and parental smoking were not significant. The results show that
      some of the major risk factors have the effect of raising the rectal temperature
      of sleeping infants.

PMID- 8554365
TI  - Heart transplantation for dilated cardiomyopathy.
AB  - Between 1988 and 1994, 23 patients underwent heart transplantation for dilated
      cardiomyopathy. The age of the 13 boys and 10 girls was from 8 months to 16 years
      (mean 7.1 years). Selection criteria included failure to thrive despite maximal
      antifailure treatment and/or intravenous inotrope dependence. The aetiology of
      cardiomyopathy was idiopathic (n = 13), congenital (n = 3), anthracycline induced
      (n = 4), Barth's syndrome (n = 1), and maternal systemic lupus erythematosus (n =
      2). The waiting period of heart transplantation ranged from one day to 147 days
      (mean 22 days). Maintenance immunosuppression included cyclosporin, azathioprine,
      and prednisolone. Follow up after transplantation was from one month to 62 months
      (median 27 months) with a mean actuarial survival of 95% at one year and 87% at
      three years. Four patients developed coronary artery disease, one of whom died as
      a consequence 15 months after heart transplantation. Heart transplantation has
      emerged as an acceptable therapeutic option, at least in the short term, for
      patients with dilated cardiomyopathy.

PMID- 8554366
TI  - Infantile osteopetrosis; bone marrow transplantation from a cousin donor.
AB  - The successful correction of infantile osteopetrosis in an Asian child by bone
      marrow transplantation (BMT) from an HLA-A,B matched cousin donor is reported.
      Retrospective HLA molecular analysis revealed that patient and donor were
      incompatible for HLA-DPB1. Donor type cells detected in the patient after
      transplantation indicate successful engraftment. The patient is currently alive
      and well.

PMID- 8554367
TI  - Liver transplantation for homozygous familial hypercholesterolaemia.
AB  - Homozygous familial hypercholesterolaemia is a rare inherited condition with an
      incidence of approximately one in a million. It is associated with severe
      premature atherosclerosis and early death from cardiovascular complications. The
      results of liver transplantation reported to date have suggested only partially
      effective reduction of the hypercholesterolaemia. Three boys with familial
      hypercholesterolaemia, aged 10.0 to 15.1 years, received liver grafts at
      Addenbrooke's Hospital. Their untreated fasting lipid concentrations were grossly
      raised. All three had angiographic evidence of coronary atheroma and two had
      exertional angina. One child had such severe atheroma that coronary artery bypass
      surgery was considered necessary before liver transplantation. All three had
      straightforward operative and postoperative courses and their lipid
      concentrations returned rapidly to normal. One boy developed chronic rejection
      requiring retransplantation. Currently all three boys are well, on normal diets,
      and with normal liver function. It is concluded that (1) liver transplantation
      offers highly effective treatment for this lethal condition, (2) timing the
      operation is difficult but it should be undertaken before coronary artery disease
      has progressed too far (when combined liver and heart transplantation may be the
      only possibility), and (3) in well grown children with no previous abdominal
      surgery the immediate risks of liver transplantation are low but chronic
      rejection remains a danger.

PMID- 8554368
TI  - Preparing the bowel for colonoscopy.
AB  - Bowel preparation methods for total colonoscopy in children generally involve
      whole gut irrigation with electrolyte lavage solutions, which in most children
      will require hospitalisation for nasogastric tube administration. The aim of the
      study was to determine the efficacy of oral bisacodyl combined with a single
      phosphate enema as a bowel preparation regimen in children. In an open
      prospective trial, 30 children (aged 18 months-15 years) were given oral
      bisacodyl on each morning of the two days before colonoscopy. The children were
      maintained on a normal diet. A phosphate enema was administered on the morning of
      the procedure. The adequacy of bowel preparation was graded as grade I if no
      faecal material was encountered, grade II if small amounts of faecal material
      were present in scattered locations, and grade III if there was poor preparation
      with faecal material precluding satisfactory visualisation of the bowel mucosa.
      Eight children (26.6%) had minor abdominal cramps when taking bisacodyl, but all
      had a previous history of similar pain. Five children (16.6%), all under 5 years
      of age, cried during the administration of phosphate enema. Bowel preparation was
      considered excellent (grade I) in 26 (86.6%) and good (grade II) in four (13.3%).
      In all patients adequate visualisation of the bowel mucosa was obtained. Oral
      bisacodyl combined with a single phosphate enema provides an ideal method of
      preparing the bowel for total colonoscopy. This preparation allows colonoscopy to
      be carried out as a day case procedure in children while maintaining them on a
      normal diet.

PMID- 8554369
TI  - Gastric volvulus and associated gastro-oesophageal reflux.
AB  - Between 1984 and 1994, 10 neurologically normal children between 2 and 24 months
      were diagnosed as having gastric volvulus with associated gastro-oesophageal
      reflux (GOR). The common features at presentation were episodic colicky abdominal
      pain, non-bilious vomiting, upper abdominal distension, haematemesis, and failure
      to thrive. Anterior gastropexy and conservative management of GOR was curative.

PMID- 8554370
TI  - Colposcopic genital findings in prepubertal girls assessed for sexual abuse.
AB  - After the introduction of the colposcope for the examination of children
      suspected of being sexually abused in Leeds, a study was undertaken to describe
      the findings in detail. A total of 109 consecutive prepubertal girls, mean age
      70.4 months were assessed including colposcopic genital and anal examination, and
      peer group review of reports and photographs. Fifty nine children had signs
      consistent with blunt force penetrating trauma (hymenal transection/major notch,
      scar, or hymenal attenuation). Transections were encountered most commonly at 6
      o'clock (directly posterior). In 46 the hymenal orifice was gaping with thigh
      abduction only and in 47 the hymenal orifice transverse diameter was greater than
      4 mm on labial separation. Overall, physical findings were commonly present and
      in only two cases were no signs recorded. Non-specific and frequent findings
      included patterns of labial and introital reddening. Supportive hymenal signs
      including swelling, rounding of edge, thickening, distortion, and loss of
      symmetry were common. Labial fusion was present in 20. Urethral dilatation with
      labial separation was noted in 14. Physical findings including normality are
      consistent with abuse and even minor anogenital signs as well as negative
      findings should be documented. Colposcopy and photography are valuable tools in
      peer review, teaching, and case management.

PMID- 8554371
TI  - Cognitive behaviour therapy in children and adolescents.

PMID- 8554372
TI  - Lymphadenopathy.

PMID- 8554373
TI  - Colposcopic genital findings in prepubertal girls assessed for sexual abuse.

PMID- 8554374
TI  - Transfer of critically ill patients with inhaled nitric oxide.

PMID- 8554375
TI  - Microcephaly and childhood non-Hodgkin's lymphoma.

PMID- 8554376
TI  - Ocular relapse in acute lymphoblastic leukaemia.

PMID- 8554377
TI  - Guidelines for the establishment and operation of human milk banks in the UK.

PMID- 8554378
TI  - Efficacy and cost effectiveness of inhaled steroids in asthma in a developing
      country: an epilogue.

PMID- 8554379
TI  - Altered expression of a new antigen of the dermal-epidermal junction (NU-T2 DEJ
      Ag) in junctional epidermolysis bullosa.
AB  - NU-T2 antigen (Ag) is a new and recently described antigen of the dermal
      epidermal junction, recognized by an anti-CD1b monoclonal antibody denominated NU
      T2. We studied NU-T2 Ag expression in junctional epidermolysis bullosa (13
      patients) and in other forms of hereditary epidermolysis bullosa (23 patients),
      comparing the results with nicein expression. In junctional epidermolysis bullosa
      gravis type no differences were found between the expression of NU-T2 and nicein,
      both being negative in bullous as well as in non-bullous skin. Interestingly, in
      mitis type junctional epidermolysis bullosa, NU-T2 Ag was found to be absent or
      reduced in five of six patients both in lesional and in uncleaved skin. When
      compared with nicein expression, clearcut differences were found, further
      suggesting that these two antigens are different. These data confirm that NU-T2
      Ag is a novel epitope of the dermal-epidermal junction, probably relevant in
      dermal-epidermal cohesion, and it could be responsible, together with nicein, 19
      DEJ-1 and other adhesion molecules, for the different subtypes of junctional
      epidermolysis bullosa. Finally, NU-T2 monoclonal antibody is a new relevant tool
      for the diagnosis, classification, and prenatal diagnosis of junctional
      epidermolysis bullosa.

PMID- 8554380
TI  - Altered distribution of keratinization markers in epidermolytic hyperkeratosis.
AB  - Epidermolytic hyperkeratosis (EH) is a genetic disorder of keratins associated
      with epidermal differentiation. Affected individuals carry gene mutations for
      conserved sequences of keratins K1 or K10. The structural alterations of
      tonofilaments in EH seem to be a direct consequence of the keratin gene
      mutations. EH epidermis, however, shows many other unexplained abnormalities
      including acanthosis, hypergranulosis, and hyperkeratosis. To further elucidate
      the pathogenetic mechanism of EH, we studied distribution patterns of other
      keratinization-associated molecules including involucrin, small proline-rich
      protein (SPRR) 1, loricrin and trichohyalin in the skin of four patients by light
      and electron microscopic immunohistochemistry in conjunction with conventional
      transmission electron microscopy. The middle to upper epidermal cells showed
      moderate to strong immunoreactivities to involucrin, SPRR1 and loricrin
      antibodies. Both intracellular staining and cell peripheral staining was seen for
      involucrin and SPRR1 antibodies. Loricrin labelling was prematurely associated
      with the plasma membrane of granular cells, possibly relating to abnormal keratin
      filament aggregation and cellular vacuolization. Some loricrin labelling was
      localized on the keratin aggregates, suggesting intermolecular associations
      between keratin and loricrin. Trichohyalin, hardly detectable in normal
      epidermis, was present in some granular and cornified cells in EH in association
      with keratin filaments, suggesting that it may function as an intermediate
      filament-associated protein. While cornified cell envelopes were intensely
      labelled only with loricrin antibodies in normal skin, they were immunoreactive
      to involucrin, SPRR1 and loricrin antibodies in EH. Sequential change in electron
      density of the cornified cell envelopes, a constant feature in normal skin, was
      often absent in EH. These results suggest an altered assembly process of
      cornified cell envelopes in EH.

PMID- 8554381
TI  - High affinity IgE receptor (Fc epsilon RI) expression on eosinophils infiltrating
      the lesions and mite patch tested sites in atopic dermatitis.
AB  - Expression of the high affinity IgE receptor (Fc epsilon RI) on eosinophils has
      recently been reported. This led us to evaluate Fc epsilon RI expression on
      eosinophils in atopic dermatitis (AD). Double immunofluorescence stainings with
      an anti-Fc epsilon RI monoclonal antibody (mAb) and a polyclonal antieosinophil
      cationic protein (ECP) antibody were performed on lesional biopsy specimens from
      patients with AD and from patients with bullous pemphigoid (BP) as controls. In
      AD and BP lesions, 77% and 70% of eosinophils expressed Fc epsilon RI,
      respectively. However, the intensity of Fc epsilon RI staining in AD was much
      stronger than in BP, suggesting upregulation of Fc epsilon RI expression on
      eosinophils in AD. In addition, the eosinophils infiltrating AD lesions were
      stained strongly with anti-CD23 mAb and anti-IgE antibody. At the sites of mite
      patch testing in AD, Fc epsilon RI-, CD23- and IgE-positive eosinophils were
      observed to the same degree as in the lesions, and a considerable number of mite
      antigen-bearing eosinophils were detected. Fc epsilon RI and CD23 were both
      upregulated on the skin-infiltrating eosinophils in AD and bound IgE molecules.

PMID- 8554382
TI  - Prognostic significance in malignant melanoma of nuclear DNA content measured by
      a microfluorimetric method.
AB  - The nuclear DNA content of 47 primary malignant melanomas was measured by 4',6
      diamidino-2-phenylindole-DNA (DAPI-DNA) microfluorimetry, and the DNA index, a
      quantitative measure of nuclear DNA content, was calculated. The DNA index and
      other clinical and pathological variables were examined and compared with patient
      survival using univariate and multivariate analyses. The Kaplan-Meier life table
      method revealed that the DNA index and metastases to regional lymph nodes
      significantly correlated with patient survival. A Cox proportional hazards
      multivariate analysis demonstrated that the DNA index, which was not
      significantly correlated with other variables, was the most reliable and
      independent factor for predicting patient survival.

PMID- 8554383
TI  - Triglyceride metabolism in human keratinocytes cultured at the air-liquid
      interface.
AB  - Although epidermis reconstructed in vitro histologically demonstrates the
      presence of fully differentiated tissue with cornified strata, it does not
      synthesize or release epidermal barrier lipids in the same proportions as does
      native skin, causing the barrier function to be impaired. Lipids, the content of
      which deviates the most, include triglycerides that are present in high amounts
      and stored as lipid droplets. Our recent studies have revealed that a high
      triglyceride content may be a reflection of a high synthetic rate and a low
      turnover. Therefore, the present study was undertaken to examine whether the
      triglyceride accumulation in the air-exposed cultures may be a result of
      insufficient supplementation of cells with oxygen, an excessive supplementation
      of cells with glucose, dysregulation of lipogenesis, or an impaired catabolism of
      triglycerides caused either by insufficient activity of triglyceride lipase
      and/or accumulation of free fatty acids due to insufficient activity of beta
      oxidase. When keratinocytes were cultured at the air-liquid interface in medium
      containing a standard glucose concentration, both the lactate and triglyceride
      production was high. Lowering glucose content in the medium resulted in a
      decrease in both lactate production and triglyceride synthesis. However, even
      when grown at a low glucose concentration the triglyceride content remained
      higher than found in vivo and synthesized triglycerides were stored in the cells
      as a stable pool, suggesting that the catabolism of triglycerides was impaired.
      Since both lipase and beta-oxidase were found to be active in cultured
      keratinocytes, another factor or other factors are probably implicated in the
      regulation of triglyceride metabolism.

PMID- 8554384
TI  - Feasibility of in vitro culturing of lesional psoriatic keratinocytes in medium
      containing high calcium concentrations.
AB  - Lesional psoriatic keratinocyte (LPK) culture is considered to be difficult under
      high-Ca2+ conditions in the absence of special proliferative agents. Using a
      permeable collagen membrane, we obtained a culture of LPKs under high-Ca2+
      conditions without any special proliferative agents. Single-cell suspensions were
      prepared from the epidermis of chronic psoriatic plaques. Cells were inoculated
      on the collagen membrane suspended slightly above the bottom of a Petri dish. We
      used a culture medium of Eagle's MEM containing 10% fetal calf serum. LPKs
      attached to the membrane 12 h after inoculation and gradually spread. They
      reached a confluent state by the 10th day of culture. We measured the
      concentrations of TGF alpha and IL-6 in the medium of LPKs, and compared these
      with the concentrations in normal keratinocyte (NK) cultures. Significantly
      increased secretion of TGF alpha by LPKs was observed during the initial phase
      but this secretion subsequently decreased. Concentrations of IL-6 were below the
      detectable level in both of NKs and LPKs throughout the observation period. Our
      results demonstrate that cultured LPKs under high-Ca2+ conditions secrete a
      larger amount of TGF alpha but not IL-6. Our cell culture system, which allows
      LPKs to spread and stratify, contributes to the study of the pathogenesis of
      psoriasis.

PMID- 8554385
TI  - Zinc and the mitosis-inhibitory epidermal pentapeptide (EPP) form a stimulatory
      chelated dimer.
AB  - A single intraperitoneal (i.p.) injection of picomolar doses of the epidermal
      pentapeptide (EPP), pGlu-Glu-Asp-Ser-GlyOH, is followed by a reversible
      inhibition of mouse epidermal cell proliferation. An equimolar mixture of zinc
      and EPP injected i.p. into hairless mice reversed the inhibitory activity,
      resulting in an immediate stimulation of epidermal G2-M cell flux. The
      stimulatory effect was strongest at the lowest dose (5 pmol). This effect was
      probably caused by a dizinc-dipentapeptide dimer, as shown by gel filtration and
      atomic emission spectrometry. When zinc was added in excess (EPP:Zn 1:9) no such
      dimer could be identified, and the mixture had no stimulatory effect. The results
      are discussed in terms of epidermal cell kinetics, and in relation to the use of
      zinc in dermatology.

PMID- 8554386
TI  - Repression of involucrin gene expression by transcriptional enhancer factor 1
      (TEF-1).
AB  - Involucrin is one of the precursor proteins of keratinocyte cornified envelope
      that is formed beneath the inner surface of the cell membrane during terminal
      differentiation. Although involucrin is specifically expressed in the upper
      squamous cells of the epidermis, the precise regulatory mechanism of involucrin
      gene expression remains unknown. Transcriptional enhancer factor 1 (TEF-1), which
      binds to SV40 enhancer, is a nuclear protein expressed in various types of cells
      including keratinocytes. Immunohistochemical study has revealed that TEF-1
      protein is highly expressed on the basal cell layer of the epidermis. To examine
      the possible regulatory mechanism of involucrin gene expression by TEF-1 protein,
      we analysed involucrin promoter activity of the INV-CAT vector, which was
      constructed by connecting the 5' upstream region of the involucrin gene (-801 bp
      upstream from the transcription start site and downstream including the
      untranslated first exon) to the chloramphenicol acetyltransferase (CAT) reporter
      gene. The INV-CAT vector was transfected to SV40-transformed human keratinocytes
      (SVHK). Cotransfection of the TEF-1 expression vector significantly repressed INV
      CAT promoter activity in a dose-dependent manner. The repression was also
      observed by transfection of the GAL4-TEF-1 vector, which was constructed by
      replacement of the TEF-1 DNA binding domain by the GAL4 activator domain. This
      suggests that TEF-1-induced repression is due to interference/squelching of a
      limiting transcriptional intermediary factor that is essential for involucrin
      expression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554387
TI  - Antioxidant defence mechanism of the skin against UV irradiation: study of the
      role of catalase using acatalasaemia fibroblasts.
AB  - To clarify the role of catalase, an antioxidant enzyme, in response to UV
      irradiation, we compared the effects of irradiation on cytotoxicity, activities
      of antioxidant enzymes, total glutathione concentrations, lipid peroxidation and
      the rate of collagen synthesis in skin fibroblasts from a patient with
      acatalasaemia and in those from a normal individual. The cells were irradiated
      with UVA (6 and 12 J/cm2 or UVB (0.5 and 1 J/cm2). Cell survival curves after UV
      irradiation were similar in cells from both subjects. Although superoxide
      dismutase activity in acatalasaemia cells was higher than in the control cells
      before irradiation, after irradiation the activity decreased in acatalasaemia
      cells (76% with 12 J/cm2 UVA, 47% with 1 J/cm2 UVB), but remained unchanged in
      control cells. Total glutathione concentrations also decreased in acatalasaemia
      cells (60% with 12 J/cm2) in response to UVA irradiation, but remained unchanged
      in control cells. Lipid peroxidation did not increase significantly in either
      cell type. The rate of collagen synthesis decreased to a similar extent in
      response to UV exposure in the two cell types (60-80% with 8.2 J/cm2 UVA, 40-50%
      with 10 mJ/cm2 UVB). We conclude from the results of cytotoxicity and lipid
      peroxidation that although acatalasaemia cells were killed by hydrogen peroxide
      at low concentrations with a single UV exposure, catalase functions only to a
      small degree as an antioxidant enzyme. There remains the possibility, however,
      that a deficiency of catalase may chronically damage the skin resulting in a
      reduced defence function of superoxide dismutase and glutathione with repeated
      exposures to UV, which is becoming more common in our daily life.

PMID- 8554388
TI  - Cutaneous lipid synthesis during late fetal development in the rat.
AB  - Lipid synthesis in fetal skin may be important both for the development of a
      mature epidermal permeability barrier and for growth. In these studies, we
      measured cutaneous cholesterol, sphingolipid and fatty acid synthesis during the
      critical period of epidermal barrier development in fetal rats to determine
      whether barrier function influences synthetic rates. In addition, the activities
      of HMG CoA reductase, serine palmitoyl transferase and acetyl coenzyme A
      carboxylase were evaluated. In whole skin, synthesis of cholesterol, ceramide,
      sphingomyelin and fatty acid decreased from day 17 to day 21 of gestation, as did
      the activity of HMG CoA reductase, serine palmitoyl transferase and acetyl
      coenzyme A carboxylase. In both the epidermis and dermis, a decrease in
      cholesterol, ceramide, sphingomyelin and fatty acid synthesis was measured over
      days 19-21 of gestation. Epidermal HMG CoA reductase activity also decreased over
      this same time period. In summary, epidermal and dermal synthetic rates and
      enzyme activity were highest early in gestation when the barrier was least
      competent and decreased as competence was achieved. Since other studies with
      mature animals have revealed that epidermal synthetic rates and enzyme activity
      are highest when barrier disruption is maximal, enhanced epidermal lipid
      synthesis precedes the establishment of a competent barrier in both fetal and
      mature rodents.

PMID- 8554389
TI  - The N-terminal amino acid sequence of the psoriasis-associated antigen, pso p27.

PMID- 8554390
TI  - Immunohistochemical localization of IL-1 alpha-, IL-1 beta-, IL-6- and TNF-alpha
      like immunoreactivities in human apocrine glands.

PMID- 8554391
TI  - [Flubiprofen vs dipyrone combined with hyoscine: the analgesic efficacy in renal
      colic].
AB  - OBJECTIVE: We compared the efficacy of flurbiprofen (NSAID) versus dipirone +
      hyoscine N-butylbromide in the treatment of nephric colic. METHODS: The study
      comprised 135 patients, aged 18 to 75 yrs, with intense nephric colic. The
      patients were observed 60 min after a single IM dose of 150 mg flurbiprofen (n =
      67) or 2 gm dipirone + 20 mg hyoscine N-butylbromide. RESULTS: Both treatment
      modalities were well-tolerated and afforded significant pain relief.
      Flurbiprofen, however, was faster-acting and superior to dipirone + hyoscine in
      the overall evaluation of good and excellent therapeutic response rates.
      CONCLUSION: The results of the study show that IM flurbiprofen is a useful
      alternative to dipirone + hyoscine N-butylbromide in the treatment of nephric
      colic.

PMID- 8554392
TI  - [Basic ideas on the diagnosis and treatment of burns of the male genitalia].
AB  - OBJECTIVES: The main characteristics of burn injuries of the male genitalia and
      the basic principles of treatment are described. METHODS/RESULTS: Of 77 patients
      in the Burns Unit of this hospital, 7 (9%) had lesions to the external genitalia.
      Four of these patients had superficial dermal (grade IIA), 2 had deep dermal
      (grade IIB) and one had total dermal or subdermal burn injuries (grade III-IV) to
      the genitalia. The superficial lesions were treated medically and deep burns
      required surgery. RESULTS: At one-year follow-up, no functional sequelae were
      observed except in the patient with total dermal burn injuries, who developed
      right testicular atrophy and azoospermia, but preserved erection and ejaculation.
      CONCLUSIONS: Burn injuries to the external genitalia are uncommon. These lesions
      do not often require surgical treatment, and usually heal spontaneously. Despite
      their dramatic appearance, cure with no cosmetic or functional sequelae is often
      the rule.

PMID- 8554393
TI  - [Inverted transitional-cell papilloma: the expression of the Ki-67 nuclear
      antigen as a prognostic factor].
AB  - OBJECTIVE: This study attempted to correlate the clinical course and outcome of
      transitional cell inverted papilloma and the number of active cell nuclei, using
      Ki-67 antigen expression to quantify nuclear activity. METHODS: We analyzed
      thirteen pathologically confirmed lesions of transitional epithelial inverted
      papilloma in 12 patients that had been treated from 1977-1994.
      Immunohistochemical labelling of the tumor was performed using Mib-1 antibodies
      (a marker for the Ki-67 cell proliferation-associated cyclin) that identify
      active cell nuclei. Then we counted the number of active nuclei per 10 fields at
      high magnification (400x). RESULTS: The tumor was localized to the bladder in 11
      cases and one case had 3 concomitant lesions in the renal pelvis. Five cases were
      associated with low grade urothelial transitional cell carcinoma, which was
      concomitant in one and asynchronous in the remaining 4 cases. One patient with
      inverted papilloma recurred and subsequently developed low grade transitional
      cell carcinoma. The elevated number of nuclei in the proliferative phase (more
      than 100 active nuclei per 10 high power fields) did not show a consistent
      correlation with good outcome. CONCLUSIONS: Treatment of inverted papilloma
      should be as in superficial transitional cell papillary carcinoma, since this
      tumor type may recur or be associated with transitional cell carcinoma. The
      lesions with a high proliferative activity, which is easily determined by Ki-67
      antigen quantification, generally have a poor outcome.

PMID- 8554394
TI  - [The reliability of computed tomography (CT) in the local (T) and lymph node (N)
      staging of kidney adenocarcinoma].
AB  - OBJECTIVES: We investigated the reliability of local (T) and lymph node (N)
      category staging of renal adenocarcinoma by CT in patients submitted to radical
      nephrectomy. MATERIAL AND METHODS: The study comprised 109 patients with renal
      adenocarcinoma who had undergone radical nephrectomy from 1986-1994. The
      preoperative staging was done using dynamic CT. Clinical staging was based on the
      CT data and pathological staging was determined by the pathological findings. All
      patients had a transperitoneal radical nephrectomy. The sensitivity, specificity,
      positive (PPV) and negative predictive values (NPV) for tumors localized to the
      kidney, perirenal fat invasion, central venous and lymphatic invasion were
      analyzed. RESULTS: The overall sensitivity rate was 67%; the sensitivity and
      specificity rates were 77% and the PPV and NPV were 89.5% and 67%, respectively,
      for tumors localized to the kidney. The sensitivity rate was 66%, specificity was
      76% and the PPV and NPV were 48.5% and 87.5%, respectively, for those with
      perirenal fat invasion. Tumors with venous spread showed a sensitivity of 90%,
      specificity of 92%, PPV 53% and NPV 99%. Concerning lymph node invasion, the
      sensitivity was 50%, specificity 96%, PPV 50%, NPV 96%. CONCLUSIONS: CT has a
      very low sensitivity and specificity in detecting fat invasion, a very high
      sensitivity and specificity for venous invasion and a low sensitivity, but high
      specificity in detecting lymphatic spread.

PMID- 8554395
TI  - [Synchronous bilateral renal oncocytoma].
AB  - OBJECTIVES: The present study reports a case of bilateral synchronous renal
      oncocytoma and reviews similar cases described in the literature. METHODS: The
      present case was incidentally discovered in an 81-year-old female during
      evaluation for GI disease. The arteriogram was suggestive of oncocytoma and was
      confirmed by aspiration biopsy. The patient refused surgery. At 42 months' follow
      up, the size and degree of invasion of both tumors remain unchanged. To our
      knowledge, only 20 cases of bilateral synchronous oncocytoma have been reported
      in the literature and only 6 of these were multifocal lesions. RESULTS: Renal
      oncocytoma, like salivary gland lesions, may spread as an advanced stage
      multifocal nodular oncocytic hyperplasia. Therefore it is not surprising to
      detect multiple synchronous or metachronous oncocytomas. CONCLUSIONS: Bilateral
      renal masses are a diagnostic and therapeutic difficulty, and even more so in the
      absence of systemic manifestations, hereditary disorders or a family history of
      renal tumor.

PMID- 8554396
TI  - [Vesicourethral dysfunction in the acquired immunodeficiency syndrome (AIDS)].
AB  - OBJECTIVES: Ten patients with AIDS and voiding disorders were assessed to
      determine the most common type of lower urinary tract dysfunction and its
      possible usefulness in detecting neurological disease. METHODS: A complete
      urodynamic evaluation was performed. RESULTS: The most common symptom was urge
      incontinence and the most common urodynamic finding was detrusor-external
      sphincter dyssynergia. Of the 5 patients found to have a neurological disorder,
      only 3 had demonstrable functional disorder of the lower urinary tract (2
      patients had detrusor hyperreflexia: one of them had a history of encephalopathy
      from HIV and the other patient had polyneuritis; the third patient had myelitis
      and a urodynamically diagnosed sympathetic decentration. CONCLUSIONS: Knowing the
      functional disorders of patients with AIDS can avoid complications and improve
      patient quality of life. Furthermore, it can be useful in detecting an existing
      neurological lesion or one that may develop in the future.

PMID- 8554397
TI  - [Urinary tract repercussions in patients with lipomeningocele: a review of 20
      cases].
AB  - OBJECTIVES: To analyze the urinary repercussions in patients with
      lipomyelomeningocele. METHODS: From 1976 to 1993, 20 patients (11 males and 9
      females), aged 12-17 years had been referred to our department. All patients were
      evaluated clinically and analytically, urodynamically and by imaging techniques
      (cystography, US or IVP). RESULTS: Neurogenic bladder dysfunction was observed in
      13 patients (65%); 4 of these patients had vesicoureteric reflux and 2 had
      residual pyelonephritic lesions. These 13 patients with neurogenic bladder were
      incontinent: 4 were on intermittent bladder catheterization, 2 patient were
      receiving oxybutinine, 3 were on intermittent catheterization+oxybutinine, and
      one patient has an artificial sphincter. Four male patients under 7 years will be
      starting intermittent catheterization. Of the patients with vesicoureteric
      reflux, 3 were treated with medication and one was submitted to surgery.
      CONCLUSIONS: Urinary tract involvement is not uncommon in these patients.
      However, it is not inevitable and the degree of severity is variable. Early
      diagnosis of neurogenic bladder dysfunction is fundamental for management.

PMID- 8554398
TI  - [Memotherm as a therapeutic device in infravesical obstruction].
AB  - OBJECTIVE: To determine the efficacy of the intraurethral mesh in the treatment
      of infravesical obstruction in patients at high surgical risk unamenable to other
      treatment modalities. METHODS: We evaluated 13 patients with obstruction and at
      high risk for conventional surgery (TURP) who underwent insertion of the
      Memotherm intraurethral prosthesis. RESULTS: The procedure was performed rapidly
      with scant morbidity and the patients were discharged from the hospital early.
      Improvement, evaluated by the IPSS-L, was referred by 84.6% of the patients at 45
      weeks follow up. Post-treatment improvement was evidenced by the absence of
      postvoiding residual urine at ultrasound in 69.2% of the patients and improved
      flowmetry in 84.6% of the patients. The early post-treatment complications
      included hematuria with irritative symptoms (80% of the patients). The mesh
      prosthesis had migrated in 15%, but could be repositioned. No case required
      removal of the prosthesis. CONCLUSIONS: This method affords a rapid and
      atraumatic solution for obstructed patients at high surgical risk. The material
      (heat sensitive nitinol) and the design of the mesh facilitate repositioning in
      the few cases in whom this had been required.

PMID- 8554399
TI  - [Definitive endourological treatment in urothelial tumors of the upper urinary
      tract].
AB  - OBJECTIVES: We reviewed our series of upper urinary tract tumors submitted to
      endoscopic management as definitive treatment. METHODS: The series comprised 18
      patients with transitional cell carcinoma of the upper urinary tract; 14 were
      treated by the percutaneous approach and 4 by ureteroscopy. All of them were
      single, papillary and low grade tumors. In 17 patients we analyzed the
      nephrostomy track for local tumoral seeding. RESULTS: The mean follow up was 29
      months. Fourteen patients remain free of recurrent disease (5-84 months); 2
      patients recurred and 2 others were diagnostic errors. No evidence of tumoral
      seeding was observed. CONCLUSIONS: Percutaneous or ureteroscopic surgery can
      achieve cure in selected cases. Local recurrence outside the urinary tract
      ascribable to percutaneous surgery appears to be unlikely.

PMID- 8554401
TI  - [A giant adrenal mass: the anatomicopathological surprise finding].
AB  - OBJECTIVE: The present study reviews the differential diagnosis of adrenal
      masses, including the uncommon forms, as the one described herein.
      METHOD/RESULTS: A patient with a giant adrenal mass that required differential
      diagnosis from other types of adrenal masses is presented. The diagnosis could
      only be made following anatomopathological analyses. CONCLUSIONS: The present
      case demonstrates that the uncommon forms of adrenal masses must be taken into
      account in the differential diagnosis, which, however, can only be confirmed by
      the pathological analysis since the findings on diagnostic imaging mimic other
      forms.

PMID- 8554400
TI  - [The dissolution of cystine lithiasis with n-acetylcysteine].
AB  - OBJECTIVE: The results of in situ dissolution of a cystine calculus is described.
      This approach was attempted in a female patient for whom surgery was not
      considered to be the best therapeutic option. METHODS: An obstructive cystine
      calculus was treated by in situ litholysis using N-acetylcysteine applied locally
      via two percutaneous nephrostomies and adjuvant oral metaphylaxis. The patient
      had a long clinical history of lithiasis that had also required surgery and a
      family history of cystinuria. RESULTS: In situ litholysis completely dissolved
      the cystine calculus and avoided the need for a complex surgery. The procedure
      and a pharmacological analysis are presented. CONCLUSIONS: In our view, this
      procedure is practical, carries minimal morbidity and should be considered in the
      management of cystine calculus.

PMID- 8554402
TI  - [Massive avulsion of the genital skin in a man. Apropos a case and a review of
      treatment].
AB  - OBJECTIVES: Massive skin avulsion of the male genitalia is relatively uncommon
      and there is no standard therapeutic approach. The foregoing prompted us to
      report on the present case and briefly review the different therapeutic
      approaches described in the literature. METHODS/RESULTS: The clinical features of
      a patient with massive genital and perineal skin avulsion that had been
      successfully treated by skin grafting are presented. CONCLUSION: The results
      reported in the literature indicate that skin grafting achieves better results
      than flaps or other methods of reconstruction in male genital trauma.

PMID- 8554403
TI  - [Inverted papilloma of the female urethra].
AB  - OBJECTIVE: Transitional cell inverted papilloma is an uncommon, generally benign
      tumor that rarely presents in the lower urinary tract. It is characterized by a
      typical inverted growth pattern and a layer of normal transitional epithelium.
      One such case is described herein. METHODS: We report on a 53-year-old female
      with transitional cell inverted papilloma of the urethra presenting as
      postmenopausal metrorrhagia. The lesion was removed surgically. RESULTS: It was a
      round-shaped, 1.5 cm diameter, polypoid lesion that was resected. Standard
      pathological analyses disclosed a trabecular type inverted papilloma.
      CONCLUSIONS: Transitional cell inverted papilloma of the female urethra is rare.
      To date it has only been reported in male patients. An additional case of this
      tumor type is described in a female patient.

PMID- 8554404
TI  - [Emphysematous pyelonephritis].
AB  - OBJECTIVES: The etiopathogenic and therapeutic aspects of emphysematous
      pyelonephritis, an uncommon disease entity, are discussed. METHODS/RESULTS: We
      describe the clinical history of a diabetic with intercurrent gas-forming
      infection in the form of emphysematous pyelonephritis that was successfully
      treated. CONCLUSIONS: This disease entity, which is almost exclusive to diabetic
      patients, is unique. It produces a type of organism that warrants early and
      aggressive treatment.

PMID- 8554405
TI  - [Cryptorchidism and testicular cancer].
AB  - OBJECTIVE: This report underscores the higher risk of testicular cancer in
      cryptorchidism. METHODS/RESULTS: A patient undergoing evaluation for sterility,
      who was submitted to orchidopexy 15 years earlier for cryptorchidism, developed a
      seminoma-like tumor one year following a testicular biopsy that was compatible
      with testicular atrophy, but with no signs of dysplasia. The literature on the
      epidemiology, pathogenesis, diagnosis, and treatment is briefly reviewed.
      CONCLUSIONS: Cryptorchidism is the single factor that carries a higher risk of
      testicular cancer. This condition has been reported to have 3.5 to 5 times
      greater risk of progressing to malignancy compared to normal descended testes.
      Although orchiopexy does not prevent the risk of malignancy, it permits earlier
      detection. The need to follow these patients closely is underscored.

PMID- 8554406
TI  - [Klinefelter's syndrome as the only pathology associated with priapism. A
      clinical case].
AB  - OBJECTIVE: An unusual case of Klinefelter's syndrome with ischemic priapism is
      described. METHODS: The clinical course of the present case is described and
      discussed. CONCLUSIONS: This unusual case cannot be completely ascribed to the
      hormonal changes in Klinefelter's syndrome, although hormone imbalance may have
      favoured the development of ischemic priapism.

PMID- 8554407
TI  - [Primary amyloidosis localized in the bladder].
AB  - OBJECTIVE: We report a case of localized amyloidosis of the urinary bladder in an
      80-year-old female whose main presenting symptom was massive hematuria. METHODS:
      Cystoscopic examination revealed a tumor on the trigone and bladder neck. A
      transurethral resection of the tumor was performed and the fragments were
      processed for histopathological study with hematoxylin-eosin and Congo red
      staining and ultrastructural study. RESULTS: The histopathological analyses
      disclosed large eosinophilic deposits in the submucosa with birefringence under
      polarized light in Congo red staining. Electron microscopy revealed a meshwork of
      filaments typical of amyloid. The patient had no symptoms or signs of systemic
      disease and remains symptom-free four years later. CONCLUSIONS: Primary localized
      amyloidosis of the urinary bladder is a rare condition that can be successfully
      treated surgically and has an excellent prognosis.

PMID- 8554408
TI  - A new endoscopic technique for non deflating Foley balloon.
AB  - OBJECTIVE: To describe a new technique to deflate impacted Foley balloon. METHOD:
      A total endourologic method using urethrotome sheath, ureteric catheter, stylet,
      sedoanalgesia needle and cold cup biopsy forceps is described. The technique
      involves minimal maneuverability of urethra. RESULTS: The technique is non
      traumatic, simple, and successful in almost all cases. This technique requires
      urology instruments which are easily available at any centre. CONCLUSION: The
      described technique is safe, effective non traumatic and can easily be used in
      cases of impacted Foley balloon. There is no damage to the posterior urethra.

PMID- 8554409
TI  - Current status of conventional (open) cholecystectomy versus laparoscopic
      cholecystectomy.

PMID- 8554410
TI  - Delay in presentation accounts for the majority of inflamed appendices.

PMID- 8554411
TI  - Localized study indicated in a patient with untreated pHPT is to localize an
      experienced parathyroid surgeon.

PMID- 8554412
TI  - Determine whether 1 week of total parenteral nutrition (TPN) in healthy subjects
      alters systemic responses to a subsequent dose of endotoxin.

PMID- 8554413
TI  - Hormonal therapy for gastrointestinal cancer.

PMID- 8554414
TI  - Current treatment of severely burned patients.
AB  - OBJECTIVE: The authors provide an update on a multidisciplinary approach to the
      treatment of severely burned patients. A review of studies and clinical trials
      from the past to the present include fluid resuscitation, sepsis, immune
      function, hypermetabolism, early excision, wound healing, scar formation, and
      inhalation injury. SUMMARY BACKGROUND DATA: Advances in treating initial burn
      shock, infection control, early wound closure, and modulation of the
      hypermetabolic response have decreased morbidity and mortality in the last two
      decades. Specialized burn care centers, using a multidisciplinary approach, not
      only successfully treat large burns and their complications, but provide the
      necessary rehabilitation and psychological support required for readjustment back
      into society. CONCLUSIONS: Thermal injury results in a number of physiologic
      alterations that can be minimized by adequate fluid resuscitation to maintain
      tissue perfusion, early excision of burn wounds, and rapid wound coverage. These
      measures, in combination with antibiotic coverage and nutritional support in the
      form of early enteral tube feedings, will decrease the hypermetabolic response
      and the incidence of sepsis that can lead to hemodynamic instability and organ
      failure. Ongoing clinical trials using anabolic agents (e.g., recombinant human
      growth hormone) and pharmacologic agents that modulate inflammatory and endocrine
      mediators (e.g., ibuprofen and propranolol) show promise in the treatment of
      severe burn injuries.

PMID- 8554415
TI  - Methods, indications, and results of percutaneous choledochoscopy. A series of
      161 procedures.
AB  - OBJECTIVE: Nonsurgical methods for evaluation and treatment of the biliary tree
      are usually done under fluoroscopic guidance. Direct visualization of the bile
      ducts, that is, choledochoscopy, could provide a more precise method with which
      to perform these maneuvers. The methods, indications, and results of percutaneous
      choledochoscopy are discussed from a series of 161 procedures performed in 123
      consecutive patients. METHODS AND RESULTS: Ninety-six patients had transhepatic
      drains and 27 had T-tubes implanted. Biopsy of bile duct stenosis was conducted
      in 52 cases. The sensitivity for the diagnosis of malignancy was 78%, and the
      authors recommended this method in case of nonsurgical treatment of stenosis.
      Gallstone extraction was performed in 75 cases (35 intrahepatic). Lithotripsy was
      necessary for 64 patients and complete gallstone clearance was obtained for 69
      patients (92%). The rate of stone recurrence was 18.1% (median follow-up, 32
      months), prompting the authors to reconsider surgery for the treatment of
      underlying disease. Laser photocoagulation was used successfully for two of three
      patients to ablate an intraductal adenoma. In eight cases of cholangiocarcinoma,
      the laser effect was too short to satisfactorily relieve obstruction of the
      intrahepatic bile ducts. Morbidity dramatically decreased from 53.7% to 5% when
      progressive dilation of the tract, aseptic conditions, and general anesthesia
      were applied systematically. CONCLUSION: Percutaneous choledochoscopy can be used
      routinely, provided that strict techniques are adhered to. This procedure should
      be reserved for only a small subset of biliary diseases.

PMID- 8554416
TI  - Early versus delayed laparoscopic cholecystectomy for treatment of acute
      cholecystitis.
AB  - OBJECTIVE: The current study compared the results of early versus delayed
      laparoscopic cholecystectomy for treatment of acute cholecystitis. SUMMARY
      BACKGROUND DATA: Although recent reports have suggested the use of laparoscopic
      cholecystectomy for acute cholecystitis, the complication and conversion rates
      remain high. No data are available on whether initial medical treatment can
      improve the results. METHOD: Among 497 patients who underwent laparoscopic
      cholecystectomy, 52 (10.5%) had a clinical diagnosis of acute cholecystitis
      confirmed by ultrasonography. Twenty-seven of these patients had early surgery,
      that is, within 120 hours of admission, and 25 had interval cholecystectomy after
      initial medical treatment. RESULTS: The early group required modifications in
      operative technique more frequently (p < 0.001). The conversion rate (7.4%) and
      minor complication rate (22%) were comparable. Successful early laparoscopic
      cholecystectomy required a longer operative time (137.2 minutes vs. 98.0 minutes;
      p < 0.05) and postoperative hospital stay (4.6 days vs. 2.5 days; p < 0.005) but
      reduced the total hospital stay (6.4 days vs. 12.4 days; p < 0.001). CONCLUSIONS:
      Early laparoscopic cholecystectomy for the treatment of acute cholecystitis has
      no adverse effect on complication and conversion rates. Although it is
      technically demanding and time consuming, this procedure provides the economic
      advantage of a markedly reduced total hospital stay.

PMID- 8554417
TI  - Progress toward hormonal therapy of gastrointestinal cancer.
AB  - OBJECTIVE: The authors discuss ongoing research to determine the mechanisms by
      which peptide hormones regulate growth of gastrointestinal cancer and ways in
      which this information might be used to develop noncytotoxic therapy. SUMMARY
      BACKGROUND: Approximately 100,000 people die of cancer of the gastrointestinal
      (GI) tract each year. Surgery is curative only when the tumor is localized.
      Chemotherapy and radiotherapy have limited efficacy for locally advanced or
      widespread disease. Various peptide hormones regulate the growth of these tumors.
      As for breast and prostate cancer, the growth regulatory effect of these hormones
      is being studied as a potential mechanism of hormonal therapy. CONCLUSION: Gut
      peptide hormones regulate the growth of GI malignancies through all-specific
      receptors and signal transduction pathways. Interruption or modification of these
      growth regulatory mechanisms may lead to specific noncytotoxic therapy. In
      combination with surgical extirpation, such hormonally based treatment may be
      curative of advanced GI cancer.

PMID- 8554418
TI  - Mechanisms of gastric and esophageal perforations during laparoscopic Nissen
      fundoplication.
AB  - OBJECTIVE: The purpose of this study was to determine possible mechanisms of 17
      gastric and esophageal perforations that occurred during laparoscopic Nissen
      fundoplication. METHODS: Specific details of each perforation relating to
      mechanism of injury, surgeon experience, diagnosis, treatment, and outcome were
      obtained. For each perforation, an attempt was made to accurately determine the
      mechanism of perforation. RESULTS: Three mechanisms accounted for the 17
      perforations, the majority of which occurred within the first ten laparoscopic
      Nissen fundoplications performed by the surgeon. Ten perforations resulted from
      injuries related to improper retroesophageal dissection, five occurred during
      passage of the bougie dilator or nasogastric tube, and two occurred after surgery
      secondary to suture pullthrough. Six patients received a delayed diagnosis, which
      adversely affected outcome. Most of the perforations were successfully managed by
      primary closure and wrap to include the repair. Morbidity was significantly
      increased for perforations recognized late. One death, attributed to sepsis,
      occurred in association with a delay in diagnosis. CONCLUSIONS: Gastric and
      esophageal perforations are serious complications of the new laparoscopic method
      of Nissen fundoplication. The mechanisms of these complications are specifically
      related to limitations of the laparoscopic technique. Prevention of these
      potentially lethal complications requires a full understanding of the detailed
      anatomy of the gastroesophageal region and awareness of the recognized mechanisms
      of perforation.

PMID- 8554419
TI  - Long-term follow-up after curative surgery for early gastric lymphoma.
AB  - OBJECTIVE: This study was designed to examine the long-term survival of a
      homogenous group of patients with stage IE or IIE-1 gastric lymphoma after
      complete surgical resection. SUMMARY BACKGROUND DATA: The management of gastric
      lymphoma remains controversial. Enthusiasm for multimodality approaches for
      gastric lymphoma has lead to the current trend of using chemotherapy as primary
      treatment, thus avoiding gastric resection. Surgery, however, may result in
      improved long-term survival rates. METHODS: The records of all patients with the
      diagnosis of gastric lymphoma from 1980 to 1991 were reviewed retrospectively. Of
      106 patients examined, 34 underwent curative resection and regional
      lymphadenectomy for pathologically staged IE or IIE-1 (pN1) gastric lymphoma.
      Fifteen patients underwent surgery alone, whereas 19 also received postoperative
      adjuvant therapy. RESULTS: The median follow-up time was 74 months. The 10-year
      actuarial disease-free survival was 91% for stage IE disease (n = 23) and 82% for
      stage IIE-1 disease (n = 11). There were no operative deaths and a 26% morbidity
      rate. No difference in survival was found for those treated with adjuvant
      therapy. CONCLUSIONS: The results compare favorably to those reported with the
      use of primary chemotherapy and radiation therapy and suggest that surgery
      remains the best frontline therapy for early gastric lymphoma.

PMID- 8554420
TI  - The role of tumor necrosis factor and nitric oxide in the acute cardiovascular
      response to endotoxin.
AB  - OBJECTIVE: This study was designed to examine the differential effects of tumor
      necrosis factor (TNF) and nitric oxide on the acute cardiovascular changes that
      occur in response to endotoxemia. SUMMARY BACKGROUND DATA: Recent studies have
      suggested that some, if not all, of the cardiovascular effects of TNF are
      mediated through release of nitric oxide. However, the mechanisms through which
      TNF and nitric oxide induce hypotension and shock in vivo in response to systemic
      endotoxemia remain poorly characterized, despite current interest in the use of
      nitric oxide antagonists to ameliorate septic shock. METHODS: A reproducible
      model of endotoxemia was established in adult Sprague-Dawley rats. The acute
      cardiovascular changes that occur after bolus infusion of endotoxin was then
      determined in rats treated with either TNF antibody, N-methyl arginine, or both.
      RESULTS: Inhibition of either TNF or nitric oxide restores mean arterial blood
      pressure to normal after endotoxemia (p < 0.05). However, nitric oxide exerts its
      effects principally on the peripheral vasculature, whereas TNF appears to act on
      the myocardium. A combination of TNF antiserum pretreatment and N-methyl arginine
      administration is necessary to return mean arterial blood pressure to normal 60
      minutes after endotoxin infusion. CONCLUSION: Tumor necrosis factor and nitric
      oxide mediate the acute cardiovascular effects of endotoxemia through distinct
      mechanisms. Nitric oxide is released as a result of both TNF-dependent and TNF
      independent mechanisms, whereas the cardiovascular effects of TNF are only
      partially mediated through nitric oxide.

PMID- 8554421
TI  - Factors associated with the development of candidemia and candidemia-related
      death among liver transplant recipients.
AB  - OBJECTIVE: The authors' objective was to identify factors associated with
      candidemia and candidemia-related death among adult liver transplant recipients.
      SUMMARY BACKGROUND DATA: Invasive candidiasis is the most common severe fungal
      infection occurring after liver transplantation and is associated with high
      morbidity and mortality rates. Although candidemia is not always found during
      invasive candidiasis, it has been considered as an indicator of invasive
      candidiasis in immunocompromised patients. METHODS: A time-matched case-control
      study of 26 patients with candidemia, which was defined as the isolation of
      Candida from at least one blood culture, and 52 control patients without
      candidemia was reported. Two control patients were matched with each case patient
      regarding time of transplantation and duration of follow-up. RESULTS: Between
      December 1985 and December 1992, candidemia developed in 1.4% of adult liver
      transplant recipients a median of 25 days after transplantation (range, 2-1690
      days). The overall mortality rate among patients with candidemia was 81%, and 71%
      of these deaths were related to candidemia. Conditional logistic regression
      analysis was used to identify factors associated with candidemia, which were 1)
      hyperglycemia treated with insulin up to 2 weeks before candidemia (odds ratio
      [OR], 16.15; p = 0.002), and 2) exposure to more than three different intravenous
      antibiotics before development of candidemia (OR, 11.15; p = 0.005). The
      variables predictive of death related to candidemia were abdominal surgery
      performed up to 1 week before candidemia (relative risk [RR], 7.25; p = 0.02),
      high white blood cell count (RR, 1.10; p = 0.01), lower platelet count (RR, 0.99;
      p = 0.02), and elevated AST with candidemia (RR, 1.001; p = 0.01). CONCLUSIONS:
      Hyperglycemia that requires insulin and exposure to more than three antibiotics
      are the factors associated with the development of candidemia in liver transplant
      recipients. When candidemia develops shortly after abdominal surgery and in
      patients with elevated AST, high white blood cell count, or low platelet count,
      it is associated with a high mortality rate.

PMID- 8554422
TI  - Changes in hepatic lobar function after right portal vein embolization. An
      appraisal by biliary indocyanine green excretion.
AB  - OBJECTIVE: The changes in the functional capacity of the hepatic lobe after right
      portal vein embolization (RPE) were investigated in patients with complete
      obstruction of the hepatic hilus who had undergone multiple percutaneous
      transhepatic biliary drainage catheterizations. METHODS: After injection of 0.5
      mg/kg of indocyanine green (ICG), bile draining from each hepatic lobe was
      collected separately for 6 hours. Biliary ICG excretion in each hepatic lobe was
      estimated and compared with hepatic lobar volume measured by computed tomographic
      volumetry before and an average of 11 days after RPE. RESULTS: Right portal vein
      embolization produced a significant increase in bile volume and biliary ICG
      concentration in the left lobe, resulting in a significant increase in ICG
      excretion in the left lobe. The percentage of ICG excretion in the left lobe to
      the whole-liver excretion showed a mean increase of 20.1%, which was
      statistically significant. In contrast, the percentage of left lobar volume to
      the total liver volume increased by only 8.3%. CONCLUSIONS: Measurement of
      biliary ICG excretion is useful for estimating changes of hepatic lobar function
      and has revealed that within 11 days RPE enhances functional capacity in the left
      lobe compared with volume gain without affecting total liver function.

PMID- 8554423
TI  - Route of nutritional supply influences local, systemic, and remote organ
      responses to intraperitoneal bacterial challenge.
AB  - OBJECTIVE: The authors' aim was to investigate whether antecedent nutritional
      routes influence immune responses after surgical insult. SUMMARY BACKGROUND DATA:
      Total parenteral nutrition (TPN) may influence host responses to infection. To
      the best of the authors' knowledge, however, no study has focused on the
      mechanisms underlying the influence of nutritional route on local, systemic, and
      remote organ (lung) responses after surgical insult. METHODS: Sixty-eight rats
      were divided into TPN and total enteral nutrition (TEN) groups. The two groups
      received identical nutrients for 7 days and were then challenged
      intraperitoneally with 3 x 10(8) Escherichia coli. In the first experiment, the
      rats were observed for survival. In the second experiment, the rats were killed
      before (0 hours) challenge or 2 or 6 hours after challenge. Peritoneal exudative
      cells (PEC) and bronchoalveolar cells (BALC) were harvested and cultured in
      vitro. Colony-forming units of bacteria in the peritoneal lavage fluid (PLF) were
      determined. Tumor necrosis factor (TNF), interleukin-1 alpha (IL-1 alpha),
      interferon-gamma (IFN-gamma) levels in serum, PLF, bronchoalveolar lavage fluid
      (BALF), and cell culture supernatants were measured. RESULTS: The 48-hour
      survival rate was higher in TEN than in TPN rats. Local immunity was depressed in
      the TPN group. Bacterial colony counts in PLF were significantly higher in the
      TPN group than in the TEN group after challenge. The number of PECs was
      significantly lower, and at 2 hours, local cytokine (TNF and IL-1 alpha)
      responses were diminished in the TPN group compared with the TEN group at 2
      hours. The number of PECs showed a significant positive correlation with levels
      of local cytokines in the TEN group but not in the TPN group. Elevation of local
      IFN-gamma was significant from 0 to 6 hours in the TEN group but not in the TPN
      group. In vitro production of TNF by PEC was impaired in the TPN rats before
      challenge. Remote organ (lung) responses were suppressed in the TPN group. The
      number of BALCs and the TNF levels in BALF declined significantly between 0 and 2
      hours in the TEN group but not in the TPN group. Interferon-gamma levels in BALF
      were higher in the TEN group than in the TPN group at 2 hours. Systemic cytokine
      responses were disturbed in the TPN group. Production of systemic TNF was
      greater, but the IFN-gamma response was diminished in the TPN group compared with
      the TEN group after intraperitoneal bacterial challenge. CONCLUSION: Local,
      systemic, and remote organ (lung) immune responses to intraperitoneal bacterial
      challenge are suppressed in TPN-treated animals, leading to poor survival after
      challenge. Enteral nutrition before surgical insult may enhance host immune
      responses after the insult as compared to parenteral nutrition.

PMID- 8554424
TI  - Specific acceptance of fetal bowel allograft in mice after combined treatment
      with anti-intercellular adhesion molecule-1 and leukocyte function-associated
      antigen-1 antibodies.
AB  - OBJECTIVE: The aim of this study was to see whether tolerance could be induced by
      simultaneous administration of monoclonal antibodies (MoAbs) to intercellular
      adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1)
      after transplantation of fetal small bowel between fully incompatible mice
      strains. METHODS: Fetal small bowel from either BALB/c (H-2d) or C3H/He (H-2k)
      mice was transplanted into the space between the peritoneum and rectus abdominis
      of adult C3H/He recipient mice. Syngeneic (n = 6) and two allogeneic transplant
      groups were made. In one of the allogeneic groups (n = 8), no immunosuppressant
      was given. In the other allogeneic group (n = 13), both anti-LFA-1 and anti-ICAM
      1 MoAbs (50 micrograms each/mouse/day) were given intraperitoneally after
      transplantation for the first 4 weeks. In the syngeneic and untreated allogeneic
      groups, all mice were killed 4 weeks after transplantation. In the treated
      allogeneic group, eight mice were killed 6 weeks after cessation of the MoAb
      treatment. At the time the mice were killed, the bowel graft as well as the
      recipient spleen were taken for histologic analysis and cytotoxic T-lymphocyte
      (CTL) assay, respectively. Each mouse in the remaining treated five mice was
      transplanted with BALB/c and C57BL/6 (as third-party) full-thickness skin
      simultaneously 8 weeks after cessation of the MoAb treatment. RESULTS: All grafts
      in the syngeneic group survived with normally developing villi, whereas all
      grafts in the untreated allogeneic group disappeared. In the treated allogeneic
      group, all allografts developed normal mucosa without any sign of rejection.
      Splenocytes from the recipient mice in the untreated allogeneic group showed
      increased CTL induction against donor-type alloantigen (p < 0.005), compared with
      that in the syngeneic group. Suppressed CTL induction against donor-type
      alloantigen was observed in the treated allografted recipient (p < 0.001),
      whereas CTL induction against third-party alloantigen was intact (p = NS). Third
      party skin graft was normally rejected within 10 days, whereas donor-type skin
      graft was accepted in all mice tested. CONCLUSIONS: Specific tolerance for fetal
      bowel allografts could be induced by a relatively short-term treatment with anti
      ICAM-1 and anti-LFA-1 MoAbs. This mode of immunointervention could perhaps be
      applied to humans undergoing small-bowel transplantation.

PMID- 8554425
TI  - Effect of interferon alpha IIb on the activity of sialyltransferase in testis
      homogenates of adult rats.
AB  - Interferon alpha IIb was injected to adult male rats at doses ranging from 10,000
      to 200,000 units. Animals were dissected at intervals of 12 h, 24 h, and 5 days.
      The activity of the enzyme sialyltransferase in testis homogenates was estimated.
      In the majority of experiments enzyme activity decreased in comparison to
      controls.

PMID- 8554426
TI  - Electrophoretic modification of sperm plasma membrane by ventral prostate
      secretion in golden hamsters.
AB  - Plasma membrane proteins were extracted either from epididymal spermatozoa after
      incubation with ventral prostate gland secretion or from spermatozoa recovered
      from uteri of females mated with surgically treated males belonging to the
      following groups: TX (excision of all accessory sex glands, ASG), VPX (bilateral
      excision of ventral prostate), VP (bilateral excision of all ASG except the
      ventral prostate), and SH (sham-operated). Incubation of spermatozoa with ventral
      prostatic secretion resulted in an 11-fold increase in glycoprotein content of
      the plasma membrane, but total protein concentration remained unchanged. The in
      vivo study indicated that interactions of ASG secretions and spermatozoa were
      complicated by the presence of uterine secretions. Glycoprotein content was
      reduced in the presence of ventral prostatic secretions. SDS-PAGE profiles showed
      that both uterine and ASG secretions could modify proteins on the sperm surface.
      Enrichment of a 25-kD subunit was apparently effected by uterine secretions and
      further promoted by combined secretions of the ampullary gland, coagulating
      gland, dorsolateral prostate, and seminal vesicle, but was reduced by the ventral
      prostate. A number of other protein subunits appeared to be specifically modified
      by the ventral prostate, while other ASG secretions were also shown to alter the
      effects of the ventral prostate on the sperm surface.

PMID- 8554427
TI  - Immunoinfertility: a case study with implications for immunocontraception.
AB  - A detailed case history was compiled on a couple who have had primary infertility
      for more than 20 years. The history and further laboratory investigations
      indicated that the infertility was caused by high-titre sperm antibodies in the
      female. The antibodies blocked sperm-zona binding and reacted with a prominent
      band at 65 kD in Western blots. Preliminary studies indicate that a subset of the
      patient's antibodies are specific for a unique protein sequence expressed by a
      cDNA testis library. This antigen may have potential for immunocontraceptive
      vaccine development.

PMID- 8554428
TI  - New discriminatory level for glucosidase activity to diagnose epididymal
      obstruction or dysfunction.
AB  - Neutral alpha-glucosidase activity was measured in seminal plasma of 30 patients
      consulting for infertility with a variety of disorders, and compared with 25
      normal controls. Significantly more of the study populations (asthenozoospermia,
      4/6; oligozoospermia, 3/5; azoospermia 8/15) had a neutral alpha-glucosidase
      activity less than 10 mIU/mL as compared with control samples (3/25). Also the
      mean (+/- SD) neutral alpha-glucosidase activity in patients with
      asthenozoospermia (11.7 +/- 9.2) oligozoospermia (11.3 +/- 7.2), and post
      vasectomy azoospermia (5.3 +/- 3.4) was significantly (p < .05) less than
      ejaculate from controls (21.2 +/- 14). A seminal alpha-glucosidase level of 10
      mIU/mL appears to be a useful discriminatory marker in the diagnosis of
      epididymal obstruction or dysfunction.

PMID- 8554429
TI  - Interleukin-2 in seminal plasma of fertile and infertile men.
AB  - The role of cell-mediated immunity in the etiopathogenesis of male infertility is
      far from being defined. The cytokine interleukin-2 (IL-2) has a key role in T
      cell mediated immune responses. The aim of this study was to confirm the presence
      of IL-2 in human seminal plasma, to show eventual differences between IL-2
      concentrations in fertile and infertile subjects, and to show potential
      relationship between IL-2 amounts in semen and spermiogram parameters. Forty
      three subjects entered the study, 20 with proven fertility and normal semen
      quality (fertile group) and 23 with male infertility of at least 2 years and poor
      semen quality (infertile group). IL-2 levels of seminal plasma in infertile
      subjects (444.3 +/- 40.5 fmol/mL) were significantly higher than those in fertile
      subjects (251.3 +/- 42.7 fmol/mL). There was a significant negative correlation
      between IL-2 levels and sperm count, motility, and morphology. No correlation was
      found between IL-2 levels and leukocyte count. These findings confirm IL-2 to be
      in seminal plasma, show increased IL-2 secretion in the infertile group,
      demonstrate negative correlations of IL-2 levels with main spermiogram
      parameters, and indicate no correlation with leukocyte count. IL-2 concentration
      in seminal plasma may therefore be considered as a potential marker in male
      infertility.

PMID- 8554430
TI  - Bacterial infection and semen characteristics in infertile men.
AB  - Semen samples of 190 men attending an andrology clinic were evaluated with
      bacteriological culture and categorized as negative (group I) and positive (group
      II); the effect of bacteriospemia on semen characteristics was also analyzed.
      Semen samples from both groups were simultaneously analyzed for routine
      parameters such as volume, sperm count, motility, viability and morphology. The
      semen culture was negative in 34% and positive in 66% of the samples. From 123
      samples, 157 aerobes and 8 anaerobes were recovered. The most commonly isolated
      organism was Staphylococchs epidermidis (in 63% of the samples), followed by
      Streptococchs viridans (28%), Escherichia coli (9%), Staphylococcus aureus (5%),
      Streptococcus faecalis (5%), beta-hemolytic Streptococcus (4%), and Enterobacter
      agglomerans (4%). Other microorganisms, including Klebsiella sp, Candida sp., and
      Proteus mirabilis, were recovered in fewer than 4% of the specimens. The
      comparison of semen characteristics between infected and noninfected men showed
      that motile spermatozoa and viability were lower when the microorganisms were
      present in the semen. It would appear that the bacteria can have a direct effect
      on semen quality with negative consequences in fertility.

PMID- 8554431
TI  - Human chorionic gonadotropin adjuvant therapy for patients with Leydig cell
      dysfunction after varicocelectomy.
AB  - The authors treated 135 men who underwent varicocelectomy, but had sustained
      Leydig cell dysfunction disclosed by LHRH test with human chorionic gonadotropin
      (hCG). hCG was administered for 10 weeks: 50,000 units were given in 10 divided
      doses intramuscularly. Semen analysis and measurement of serum hormone level were
      obtained 8 weeks after the completion of treatment, and every 3 months after
      that. All patients were followed up for 2 years to confirm pregnancy. Fifty-five
      percent of patients achieved pregnancy and they showed significant increase in
      sperm density, percentage of sperm motility, normal form sperm, and serum
      testosterone level. It is recommended that hCG be administered to patients who
      undergo varicocelectomy but have persistent subtle Leydig cell dysfunction
      disclosed by LHRH test to stimulate the intratesticular testosterone production.

PMID- 8554432
TI  - Enhanced levels of colony stimulating factor-1 (CSF-1) in sera and seminal plasma
      of antisperm antibody-positive infertile men.
AB  - This investigation was carried out to examine the levels of CSF-1 in sera and
      seminal plasma of fertile, immunoinfertile, and male factor-infertile men in
      order to study the role of CSF-1 in human infertility. Sera, sperm, and seminal
      plasma were analyzed for antisperm antibodies by the sperm immobilization
      technique, tray agglutination technique, and immunobead binding technique. Sperm
      motility and fertilizing capacity were analyzed by sperm motion analysis and
      sperm penetration assay, respectively. CSF-1 concentration was estimated by the
      competitive radioimmunoassay. CSF-1 was detected in sera of both fertile and
      immunoinfertile men (mean +/- SD; fertile men: 52.9 +/- 10.3 pg/mg protein;
      immunoinfertile: 58.2 +/- 19.5 pg/mg protein; p > .05). CSF-1 was also detected
      in the seminal plasma of fertile, immunoinfertile, and male factor-infertile men
      (mean +/- SD; normal fertile men: 1.7 +/- 3.5 ng/mg; immunoinfertile men: 10.9 +/
      15.6 ng/mg; male factor-infertile men: 0.85 +/- 0.25 ng/mg). The levels of CSF-1
      were highest in the immunoinfertile men, followed by those in fertile and male
      factor-infertile men. The average level in immunoinfertile men was significantly
      different from the average level in fertile or male factor-infertile men (p <
      .0001). Interestingly, the concentrations of CSF-1 per milliliter of seminal
      plasma was in general approximately 5 times greater than those in serum. These
      findings indicate that elevated seminal plasma CSF-1 concentration is correlated
      with male infertility.

PMID- 8554433
TI  - Sera gonadotropins, testosterone, and prolactin levels in men with
      oligozoospermia or asthenozoospermia.
AB  - Many previous studies evaluating various hormone levels in males with subnormal
      semen analyses were performed when the normal semen parameters were considerably
      higher than now. This study evaluated sera levels of follicle stimulating hormone
      (FSH), luteinizing hormone (LH), total testosterone (TET), free TET, and
      prolactin (PRL) in 60 males with oligospermia and decreased motility according to
      recent World Health Organization standards. Three separate groups were evaluated:
      group 1, motile density (MD) < 5 x 10(6)/mL (but not azoospermia); group 2, 5 <
      or = MD < 10 x 10(6)/mL; group 3, MD > 10 x 10(6)/mL, but % motility < 30%. There
      were no significant differences in mean FSH levels between groups. Overall FSH
      was increased in 47.1% of the cases. In contrast, mean LH levels were normal in
      all three groups. Only 17.3% of the entire group had elevated LH levels. The TET
      level was below normal in 32.3% of the entire group, with a fairly equal
      distribution between the three groups. Overall, only 7.8% had elevated PRL
      levels, with the highest percentage found in group 3 (22.2%). Only a small
      minority of patients with increased FSH had low TET levels compared to 48.0% of
      those with normal FSH. These data demonstrate that when using the lower semen
      parameters, the most common serum hormone abnormality is increased FSH; men with
      MD < 5 x 10(6)/mL do not have a higher incidence of elevated FSH than those with
      higher MDs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554434
TI  - Effects of synthetic thymosin-alpha 1 and its analogs on fertilizability of human
      sperm: search for a biologically active, stable epitope.
AB  - Thymosin-alpha 1 (T alpha 1) and six T alpha 1 analogs were synthesized to study
      structure-function relationships and to search for the biologically active and
      stable epitope(s) that would have clinical application in the treatment of male
      infertility. Four of these analogs were prepared by modification/substitution of
      N- and C-terminal amino acids of T alpha 1 peptide, and the other two analogs
      were fragments having only N-16 amino acids (N-terminal) or C-14 amino acids (C
      terminal), respectively, of the T alpha 1 peptide. T alpha 1 and these six
      analogs were tested for their effects on human sperm penetration rates in the
      sperm penetration assay (SPA). T alpha 1 significantly (p < .0001) increased the
      penetration rates in SPA, with the strongest enhancing effect at 0.5
      microgram/100 microL concentration. Of the six analogs tested only two, T alpha 1
      Gly-NH2 and T alpha 1-C14, retained the enhancing effects in SPA. None of the
      analogs decreased the penetration rates or affected sperm motility compared to
      control. The enhancing activity resides primarily in an epitope, the C-terminal
      14 amino acids of T alpha 1. However, for maximal effect both N- and C-terminal
      amino acids (serine and asparagine, respectively) have to be intact and
      unmodified. The T alpha 1-Gly-NH2 analog that had its C-terminal protected was as
      potent as the intact T alpha 1 peptide. T alpha 1 and this analog may have
      clinical applications in treatment of male-factor-mediated infertility.

PMID- 8554435
TI  - Higher pregnancy rates following treatment of cervical factor with intrauterine
      insemination without superovulation versus intercourse: the importance of a well
      timed postcoital test for infertility.
AB  - A randomized study comparing the efficacy of timed intrauterine insemination
      (IUI) without hyperstimulation to sexual intercourse was performed in women with
      cervical factor infertility. Among the strict requirements for inclusion in the
      study were a normal semen analysis in the male partner, as well as the failure to
      demonstrate any sperm with progressive forward motion in a postcoital test
      performed 8-12 h after intercourse at the time of a mature follicle. All other
      infertility factors were negative. The data demonstrated a statistically
      significant fecundity rate at 1 month when IUI was compared to intercourse (21.2
      vs. 3.9%). These data suggest that carefully timed IUI in nonhyperstimulated
      cycles is an effective treatment for cervical factor infertility.

PMID- 8554436
TI  - Effect of an intermediate hold with vapor freezing on subsequent hypoosmotic
      swelling in thawed sperm.
AB  - Cryopreservation and thawing of sperm exerts an adverse effect on functional
      integrity of the sperm membrane as measured by the hypoosmotic swelling (HOS)
      test. Supercooling using the liquid nitrogen (LN2) vapor technique may damage
      membranes by favoring ice crystal formation. Slight slowing of the cooling
      process may allow escape of intracellular fluid. This study was conducted to
      evaluate modification of the LN2 vapor technique by employing an intermediate
      hold in a freezer (to slow down the rate of cooling) on HOS scores on specimens
      thawed 1 month after freezing. Semen samples were obtained from male partners of
      infertile couples with a requirement of a baseline HOS score < 70% but > or =
      60%. The HOS test was performed on the unprepared semen sample prior to freezing
      and immediately post-thaw 1 month later on the aliquot frozen with LN2 vapors
      only vs. the equal fraction subjected to an intermediate hold. The mean initial
      HOS score was 68.5% and was 47% in thawed specimens that had been cryopreserved
      with and without an intermediate hold. There were no differences in the
      percentage of specimens exhibiting a > 50% HOS score following vapor freeze (70%)
      or vapor freeze with a hold (74%). Thus, these data do not demonstrate any
      advantage of slowing the vapor freezing process by utilizing an intermediate
      hold.

PMID- 8554437
TI  - Cytopathology and the pathology resident. A survey of residency program
      directors.
AB  - OBJECTIVE: To collect information on the status of cytopathology training in the
      United States. DESIGN: Questionnaire survey mailed in June 1994. SETTING:
      Pathology residency training programs in the United States. PARTICIPANTS:
      Pathology residency directors. MAIN OUTCOME MEASURES: Training length, numbers of
      cytology specimens, teaching methods and topics, and graduated responsibility.
      RESULTS: Of the 196 surveys mailed, 101 (52%) programs responded. The average
      length of required training was 3 months. The perceived optimal training time
      averaged 4.5 months, however, with 80% of programs requiring less than their
      stated optimum. The median numbers of gynecologic, nongynecologic, and fine
      needle aspiration biopsy specimens examined per resident were 1100, 500, and 200,
      respectively. Cytopreparatory techniques, laboratory management, computer
      systems, and immunocytochemistry were included in over 75% of cytopathology
      training programs. Teaching at the microscope was rated as the most important
      teaching method by 90% of respondents. The majority of senior residents performed
      fine-needle aspiration biopsy procedures and screened and signed out cases with
      direct faculty supervision, but fewer than 20% of programs allowed senior
      residents to independently sign out specimens. CONCLUSIONS: Recommendations based
      on this review include a minimum training time of 3 months, improved training in
      both fine-needle aspiration biopsy techniques and gynecologic cytology,
      continuous exposure to cytopathologic techniques, and increased graded
      responsibility for senior residents.

PMID- 8554438
TI  - Mantle cell lymphoma. Accurate diagnosis yields new clinical insights.

PMID- 8554439
TI  - Direct LDL. A cost-effective replacement for the Friedewald equation?

PMID- 8554440
TI  - Indications and immediate patient outcomes of pathology intraoperative
      consultations. College of American Pathologists/Centers for Disease Control and
      Prevention Outcomes Working Group Study.
AB  - OBJECTIVE: To evaluate the reasons (indications) for and immediate intraoperative
      surgical results (outcomes) associated with pathology intraoperative
      consultation. DESIGN: In 1992 and 1993, surgeons collaborated with pathologists
      in 472 voluntarily participating institutions from the United States (462),
      Canada (7), Australia (2), and New Zealand (1) in a study jointly sponsored by
      the College of American Pathologists and the Centers for Disease Control and
      Prevention. Pathologists selected 20 consecutive intraoperative consultations and
      assembled a cover letter, a checklist questionnaire, and a copy of the
      corresponding surgical pathology report, all of which were sent to the surgeon(s)
      for retrospective evaluation. PARTICIPANTS: The study was distributed to
      participants in the College of American Pathologists voluntary Q-Probes quality
      improvement and Surgical Pathology Performance Improvement programs and to
      Canadian and Australian hospitals with more than 200 beds. RESULTS: Evaluation of
      9164 cases established the five most common indications for intraoperative
      consultation: (1) establish or confirm diagnosis to determine type or extent of
      operation (51%), (2) confirm adequacy of margins (16%), (3) confirm nature of
      tissue to direct sampling for immediate culture or other laboratory study (10%),
      (4) expedite obtaining diagnosis to inform family or patient (8%), and (5)
      confirm sufficient tissue submitted to secure diagnosis in permanent section
      (8%). The information provided by the intraoperative consultation resulted in
      changed surgical procedures that were either modified, terminated, or newly
      initiated in 47%, 30%, 6%, 9%, and 28% of cases, corresponding respectively to
      each of the above five common indications. Rarely cited reasons for
      intraoperative consultation were to expedite obtaining diagnosis for surgeon's
      knowledge (3%), to facilitate patient management, other professional
      communication or discharge planning prior to permanent section availability (3%),
      academic protocol (< 1%), and consultation not needed or no reason for request (<
      1%). CONCLUSIONS: This multi-institutional, interdisciplinary database confirms
      that pathology intraoperative consultations, regardless of the initial
      indications, influence immediate patient care decisions, resulting in changed
      surgical procedures in an average of 39% of all operative cases.

PMID- 8554441
TI  - Peripheral nerve biopsies.
AB  - Nerve biopsies require special handling procedures that may not be familiar to
      many surgical pathologists. Most pathology laboratories handle fewer than 10
      nerve biopsies per year, often referring them to specialized laboratories for
      evaluation. However, initial handling procedures may affect the ability of the
      reference laboratory to evaluate the specimen, and the remote location may impede
      communications and increase the time required for diagnostic evaluation. In a
      recent needs assessment questionnaire conducted by the College of American
      Pathologists, a need for understanding the handling of peripheral nerve biopsies
      was identified. Reference laboratories reported that clinical history and
      electrophysiologic data are very helpful, both in planning the handling of the
      biopsy and in interpreting the findings. Understanding the clinical differential
      diagnosis and the relationships between the differential diagnosis and the use of
      specialized studies often helps in the initial handling of peripheral nerve
      biopsies, whether evaluated locally or referred to a specialized laboratory. In
      this paper, we offer some general guidelines for handling nerve biopsies,
      including the rationale for the studies commonly used to evaluate them. With this
      background, decisions may be made about handling specimens that are specific for
      the clinical situation and allow for the highest diagnostic yield and fastest
      turnaround times.

PMID- 8554442
TI  - Leukemic phase of mantle cell lymphoma two case reports and review of the
      literature.
AB  - Two cases of mantle cell lymphoma are presented. Both patients were women, aged
      68 and 56 years, who presented with lymph node enlargement. Each case was
      initially interpreted as a follicular small cleaved cell lymphoma. Both patients
      later presented with splenomegaly and recurrent lymphadenopathy. Morphologic and
      immunologic studies on a parotid swelling in one case and a splenectomy specimen
      in the other indicated a diagnosis of mantle cell lymphoma. Both women
      subsequently presented in leukemic phase associated with a poor prognosis, and
      both patients succumbed soon after. The characteristics, differential diagnosis,
      and leukemic phase of mantle cell lymphoma are discussed. The importance of
      appropriate immunohistochemical and flow cytometry analysis in distinguishing
      mantle cell lymphoma from morphologically similar follicular center cell
      lymphomas is demonstrated.

PMID- 8554443
TI  - Characterization of postcardiac transplant lymphomas. Histology,
      immunophenotyping, immunohistochemistry, and gene rearrangement.
AB  - OBJECTIVE: Between 2% and 9% of cardiac transplant recipients develop
      posttransplant lymphoproliferative disease, which includes lymphomas. These are
      usually aggressive Epstein-Barr virus-associated B-cell proliferations similar to
      those seen in other immunodeficiency states. A retrospective pathologic study of
      the tumor tissue from 21 cardiac transplant recipients with posttransplant
      lymphoproliferative disease was undertaken. DESIGN: Tumor histology,
      immunohistochemistry, immunophenotyping, and DNA analysis for clonal gene
      rearrangement and the presence of Epstein-Barr virus DNA were performed.
      PATIENTS: The mean patient age was 53.4 +/- 10.2 years (range 33-67 years); 33%
      of the patients were alive at the time of study. RESULTS: Histologically, the
      samples comprised one Burkitt's lymphoma, three diffuse mixed lymphomas, eight
      diffuse large-cell lymphomas, and nine immunoblastic lymphomas. Thirteen (93%) of
      14 samples were infiltrated by small reactive T cells; five of the lymphomas
      qualified as T-cell rich. Of 14 cases studied, 12 had clonal immunoglobulin gene
      rearrangements, 1 had oligoclonal bands, and 1 exhibited only a germline pattern.
      The B cells were CD10+, CD19+, and CD20+, and the reactive T cells were CD2+,
      CD3+, CD5+, CD7+, CD8+, and CD57+ by immunophenotyping. CONCLUSIONS: In this
      patient series, morphologically aggressive lymphomas and disseminated disease
      occurred early as well as late after transplantation. Most of the tumors showed a
      reactive T-cell component, which may represent a host attempt at controlling the
      B-cell proliferation.

PMID- 8554444
TI  - The lack of value of repeated Clostridium difficile cytotoxicity assays.
AB  - OBJECTIVE: To determine the value of repeated Clostridium difficile cytotoxicity
      assays (CA). DESIGN: All CAs performed during 1993 were retrospectively reviewed
      and correlated with clinical data. Assays were grouped into episodes, which were
      defined as one or more successive tests performed on a single patient within 7
      days or less of each other. SETTING: A 751-bed tertiary care facility. PATIENTS:
      All patients with Clostridium difficile CAs submitted to the microbiology
      laboratory. RESULTS: There were 947 episodes with two or more CAs. In 15 of these
      episodes, a negative CA result was followed by a positive result, and in 25
      cases, a positive result was followed by a negative one. We reviewed the clinical
      data for these cases. Of the 947 episodes with two or more CAs, the repeated
      assays provided new information that was used in patient care in fewer than nine
      cases. Repeated testing within 7 days of an initial CA accounted for 36% of all
      assays performed, but provided clinically useful information in only about 1% of
      cases. CONCLUSIONS: Clostridium difficile CAs should not be repeated within a 7
      day period.

PMID- 8554445
TI  - Effect of leukocyte concentration and inoculum volume on the laboratory
      identification of cytomegalovirus in peripheral blood by the centrifugation
      culture-antigen detection methodology.
AB  - OBJECTIVE: To investigate the rate of Cytomegalovirus (CMV) detection in
      peripheral blood by shell vial assay-indirect immunofluorescent assay technology
      using two leukocyte inocula concentrations and different inoculum volumes
      containing equivalent cell concentrations. DESIGN: Leukocyte inocula
      concentrations of 2 x 10(5) and 4 x 10(5) cells per 0.2 mL were assayed for the
      presence of CMV by shell vial assay-indirect immunofluorescent assay. The effect
      of different inoculum volumes (0.2 and 0.4 mL) containing an equivalent cell
      concentration of 4 x 10(5) was evaluated as well. The data were compared to
      conventional MRC-5 tube cultures, including blind passage. PATIENTS: Ninety-five
      patients (101 specimens) were tested sequentially. The test population consisted
      primarily of patients suffering from the acquired immunodeficiency syndrome.
      SETTING: The diagnostic virology laboratory, acquired immunodeficiency syndrome
      clinics, and hospital wards. RESULTS: Among the 101 specimens tested by shell
      vial assay-indirect immunofluorescent assay, the rate of CMV sensitivity
      increased by 36% using the higher leukocyte inoculum concentration of 4 x 10(5)
      cells per 0.2 mL (P = .002; Cochran's Q test). No significant difference in CMV
      yield was identified using equivalent cell concentrations with inocula volumes of
      0.2 or 0.4 mL. The CMV sensitivity rate using the higher leukocyte inoculum
      surpassed that obtained by conventional tube culture-blind passage. CONCLUSION:
      These data denote the importance of leukocyte concentration on the rate of CMV
      detection in peripheral blood by the shell vial assay-indirect immunofluorescent
      assay. The data also point out the need to establish a standardized blood
      preparation protocol to achieve optimal clinical relevance of this widely used
      laboratory test.

PMID- 8554446
TI  - Rapid accurate entry of microbiology results.
AB  - OBJECTIVE: To develop techniques to improve efficiency and accuracy of data entry
      in microbiology, using a commercially available laboratory information system
      that is keystroke-intensive. DESIGN: A combination of technologies, including bar
      coded phrase sheets, keyboard macros, and bar-coded specimen labels, are used to
      automate the entry of commonly used keystroke sequences and combinations of
      culture findings. SETTING: An acute care hospital laboratory. PARTICIPANTS:
      Laboratory technologists. OUTCOME MEASURES: Feasibility, report error rates, and
      technologist time. RESULTS: Qualitative: implementation of all three technologies
      proved feasible and practical. Quantitative: a 25-fold decrease in misreported
      cultures, as well as a 50% saving in reading time for new urine cultures.
      CONCLUSIONS: This set of technologies for keystroke reduction would be of general
      applicability to laboratories with a variety of different laboratory information
      systems.

PMID- 8554447
TI  - Extramedullary myeloid cell tumors arising in the setting of chronic
      myelomonocytic leukemia. A report of two cases.
AB  - We report two cases of extramedullary myeloid cell tumor that arose in patients
      with chronic myelomonocytic leukemia. In both cases, the tumors were difficult to
      recognize histologically because the neoplasms lacked cytological evidence of
      granulocyte maturation, such as cytoplasmic granulation or eosinophilic
      myelocytes, and the Leder stains for chloroacetate esterase were negative.
      Immunohistochemical studies were necessary to establish the correct diagnosis.
      The neoplastic cells in both tumors expressed myeloperoxidase, lysozyme, and CD43
      and were negative for B-cell, T-cell, and other nonhematopoietic antigens tested.
      We report these cases to emphasize that extramedullary myeloid cell tumors may
      rarely precede transformation to acute myeloid leukemia in patients with chronic
      myelomonocytic leukemia. Extramedullary myeloid cell tumors of monocytic lineage
      may be difficult to recognize in routine and Leder-stained sections, and
      immunohistochemical studies may be essential for establishing the diagnosis.

PMID- 8554448
TI  - Hepatic angiomyolipoma. A report of four cases with immunohistochemical and DNA
      flow cytometric studies.
AB  - OBJECTIVE: To describe the pathologic features in four cases of hepatic
      angiomyolipoma, a rare benign mesenchymal tumor of the liver. DESIGN:
      Retrospective analysis of surgical specimens from four patients, with
      immunohistochemical and flow cytometric studies. RESULTS: None of the patients
      carried a diagnosis of tuberous sclerosis. All four tumors were large and well
      circumscribed, and one patient had multiple lesions. The neoplasms were composed
      of numerous vessels and exhibited a predominance of epithelioid smooth muscle
      cells. The low amount of fat in these four cases was not sufficient to produce
      characteristic images that would allow diagnosis of angiomyolipoma before
      surgical resection. All tumors exhibited strong staining with HMB45 and anti
      smooth muscle actin antibodies, whereas no positivity was observed with estrogen
      and progesterone receptor antibodies. Flow cytometry revealed a diploid DNA
      pattern in all cases. CONCLUSIONS: Our four cases demonstrate that it is
      difficult to differentiate hepatic angiomyolipoma from other liver tumors when
      the amount of fat is low. HMB45 positivity of smooth muscle cells appears to be
      very helpful in reaching a pathological diagnosis of hepatic angiomyolipoma. The
      DNA-diploid pattern observed in all cases could be considered a new argument for
      the benign nature of hepatic angiomyolipoma.

PMID- 8554449
TI  - Expression of human Pit-1 product in the human pituitary and pituitary adenomas.
      Immunohistochemical studies using an antibody against synthetic human Pit-1
      product.
AB  - OBJECTIVE: Pit-1, a member of a family of the POU-domain DNA binding factors, has
      been known as a pituitary-specific transcriptional factor that regulates
      functional differentiation toward somatotrophs, lactotrophs, and thyrotrophs in
      the rodent pituitary gland. The aim of this study is to elucidate the role of
      human Pit-1 (hPit-1) protein in the differentiation of human pituitary adenomas,
      using immunohistochemistry. DESIGN: Anti-human Pit-1 polyclonal antibody against
      synthetic peptide was applied to perform the avidin-biotinperoxidase complex
      method on paraffin sections of 75 surgically obtained pituitary adenomas and 12
      nontumorous human pituitaries obtained at autopsy. RESULTS: In normal human
      pituitary glands, many cells were positive for hPit-1 product in the nuclei of
      somatotrophs, lactotrophs, and somatomammotrophs. Among 75 pituitary adenomas,
      hPit-1 product was expressed in 55 adenomas (73.3%). All (100%) of the growth
      hormone-positive and thyrotroph cell adenomas were positive for hPit-1 product.
      Unexpectedly, expression of hPit-1 was found in a limited number of
      adrenocorticotropic hormone-producing adenomas and clinically nonfunctioning
      adenomas, including gonadotroph cell adenomas, although localization was found
      only in occasional cells. CONCLUSIONS: The invariable expression of hPit-1
      protein in growth hormone-positive adenomas and thyroid-stimulating hormone
      positive adenomas may suggest the role of Pit-1 protein in specific
      differentiation of the adenoma cells. The expression of hPit-1 in various other
      types of adenomas may indicate the involvement of other unidentified
      transcription factors or specific mediators that have roles in these
      differentiations. Our observation may provide some insight into the origin of
      cell types of some clinically nonfunctional adenomas.

PMID- 8554450
TI  - Mucosal lymphangiectasia in gastric adenocarcinoma.
AB  - OBJECTIVE: To describe the occurrence and significance of mucosal
      lymphangiectasia in gastric adenocarcinoma. DESIGN: One hundred consecutive
      gastrectomies for adenocarcinoma were reviewed, using 25 consecutive
      gastroscopically biopsied gastrectomy specimens with peptic ulcers as negative
      controls. SETTING: The specimens were collected over a period of 25 months in two
      general hospitals and processed according to a standard protocol. PATIENTS:
      Chinese living in Hong Kong. RESULTS: Twenty cases of adenocarcinoma were found
      to show mucosal lymphangiectasia, which was arbitrarily defined as the presence
      of ectatic lymphatic channels in the lamina propria having maximum dimensions
      greater than that of a foveolar gland. The ectatic lymphatics were lined by
      simple endothelium, devoid of fibromuscular wall, and they either were optically
      empty or contained scant mononuclear leukocytes. None of the patients had
      preoperative evidence of malabsorption syndrome or protein-losing enteropathy.
      Lymphangiectasia was most readily seen in the superficial lamina propria near the
      main tumor. In 10 cases (50%), lymphangiectasia extended to the nonneoplastic
      part of the gastric mucosa, at a distance of at least 2 cm away from the main
      tumor. Tumor emboli were seen in the ectatic lymphatics in 11 cases (55%). In two
      cases (10%), the distal line of resection was involved by intramucosal lymphatic
      spread. The tumor permeating the lymphatics did not evoke any inflammatory or
      desmoplastic reaction in the perilymphatic lamina propria, similar to the
      phenomenon of so-called lymphangitis carcinomatosa. In eight cases (40%), there
      were foci beyond the main tumor where mucosal lymphangiectasia was present, but
      without tumor in its immediate vicinity. All (100%) of the 20 stomachs with
      mucosal lymphangiectasia had metastases in regional lymph nodes, whereas only 59
      of the 80 cases (73.75%) without lymphangiectasia were node-positive (P < .025).
      All node-negative cases did not show lymphangiectasia. Twenty-five consecutive
      gastrectomies for peptic ulcer disease that had undergone preoperative mucosal
      biopsies showed no lymphangiectasia, suggesting that mucosal biopsy was not the
      cause of mucosal lymphangiectasia. CONCLUSIONS: (1) Gastric mucosal
      lymphangiectasia is associated with carcinoma but not peptic ulcer, (2) Mucosal
      lymphangiectasia in gastric carcinoma signifies lymph node metastases, and (3)
      Gastric carcinoma can spread along the mucosa via intramucosal lymphatics.

PMID- 8554451
TI  - Immunophenotype of intraductal carcinoma.
AB  - OBJECTIVE: Mammography and breast-conserving therapy have focused attention on
      the classification of intraductal carcinoma (IDC) and emphasized the prognostic
      importance of comedo versus noncomedo variants. We used histochemical markers to
      define the immunophenotype of 43 IDCs with respect to comedo versus noncomedo
      status and patterns of angiogenesis. RESULTS: Reactions in comedo carcinomas were
      significantly negative for estrogen receptor and progesterone receptor, and
      positive for p53 and HER-2/neu more often than the noncomedo variant. All seven
      IDCs associated with Paget's disease showed positive reactions for HER-2/neu.
      Basement membrane immunoreactivity for type IV collagen and laminin was
      discontinuous in most examples of IDC regardless of type, with a trend toward
      more intense staining in comedo than in noncomedo carcinomas. Periductal
      angiogenesis was not significantly related to the type of IDC but was more
      pronounced with comedo carcinomas. CONCLUSIONS: These observations indicate that
      there are immunophenotypic correlates to the current structural classification of
      IDC. The immunophenotype of IDC is helpful in subclassifying an IDC and could
      prove useful as a prognostic indicator for local control in patients treated by
      breast-conserving therapy.

PMID- 8554452
TI  - Atypical Fabry's disease. An oligosymptomatic variant.
AB  - Fabry's disease is a rare, inherited, X-linked metabolic storage disease with
      ceramide hexoside due to alpha-galactosidase A deficiency. Patients with typical
      Fabry's disease usually present with several clinical manifestations of corneal
      dystrophy, neurologic abnormalities, cardiovascular disease, heavy proteinuria,
      and characteristic cutaneous angiokeratoma. However, atypical Fabry's disease
      with oligosymptomatic phenotype presents with symptoms restricted solely to
      cardiocytes or kidney and might be diagnosed by chance during a routine
      endomyocardial or renal biopsy examination. In this article, we report a case of
      Fabry's disease incidentally diagnosed in a 34-year-old man who presented with
      intermittent trace or 1(+) proteinuria only. This patient had no history of renal
      disease in any other family member. A renal biopsy to evaluate trace proteinuria
      revealed histologic and ultrastructural findings compatible with Fabry's disease.
      Subsequent to the renal biopsy, a skin biopsy on a few initially unrecognized,
      scattered, dark-pinkish scrotal papules showed typical angiokeratoma. A
      biochemical enzymatic assay of alpha-galactosidase in urine and plasma revealed a
      markedly decreased enzyme level in the hemizygous range.

PMID- 8554453
TI  - Paclitaxel-induced cardiotoxicity. An ultrastructural study.
AB  - The ultrastructural appearance of the myocardium in a fatal case of paclitaxel
      induced cardiotoxicity is reported, which includes swelling of the sarcoplasmic
      reticulum, loss of myofibrils, and accumulation of lipofuscin as well as
      laminated myelinoid figures. Such changes are very similar to those seen in
      anthracycline-induced cardiotoxicity and may suggest a pathogenetic final common
      pathway. While endomyocardial biopsy is a recognized means of monitoring
      anthracycline-induced cardiotoxicity, whether more liberal use of endomyocardial
      biopsy can prevent fatal cases of paclitaxel-induced cardiotoxicity needs to be
      further assessed.

PMID- 8554454
TI  - Viability of the autopsy outside the institutions.

PMID- 8554455
TI  - Coexistence of Hodgkin's disease and giant lymph node hyperplasia of the plasma
      cell type (Castleman's disease).
AB  - Coexistence of Hodgkin's disease and giant lymph node hyperplasia (Castleman's
      disease) is well documented in the literature. We present a unique case in which
      the original lymph node biopsy revealed interfollicular Hodgkin's disease (CD15+,
      CD30+, CD45-, Reed-Sternberg cells) with coexistent histologic features of the
      plasma-cell variant of Castleman's disease. The patient experienced a long-term
      remission following combined chemotherapy and radiation therapy. He presented at
      18 years and again at 22 years later with clinical, hematologic, and histologic
      features of a multicentric plasma-cell variant of Castleman's disease without
      evidence of Hodgkin's disease. This unique case report further strengthens the
      association of Castleman's disease and Hodgkin's lymphoma. Two pathogenetic
      mechanisms for this association have been suggested: (1) secretion of interleukin
      6 by Hodgkin's Reed-Sternberg cells and histiocytes, and (2) manifestation of an
      abnormal immune state associated with Hodgkin's disease. These two mechanisms
      may, indeed, be related.

PMID- 8554456
TI  - Florid xanthomatous pelvic lymph node reaction to metastatic prostatic
      adenocarcinoma. A sequela of preoperative androgen deprivation therapy.
AB  - We describe a florid xanthomatous histiocytic reaction in the pelvic lymph nodes
      of a patient treated with androgen deprivation therapy prior to radical
      prostatectomy. The xanthomatous reaction was so marked that it nearly obscured
      the presence of metastatic carcinoma in the same lymph nodes. A similar
      histiocytic reaction was also present in association with carcinoma in the
      prostatectomy specimen, a finding that was not identified in pretreatment biopsy
      specimens. No other known cause of pronounced histiocytic lymph node
      proliferation was present in this patient. Only one brief description of a
      xanthomatous reaction in lymph nodes associated with this treatment has been
      previously recorded in the literature to our knowledge. Other patients from our
      institution who were treated similarly preoperatively all had lymph nodes
      negative for tumor, and none demonstrated a xanthomatous tissue reaction,
      suggesting that this reaction may be a marker for metastatic tumor in the same
      lymph node.

PMID- 8554457
TI  - New indole and pyridazinoindole analogs--synthesis and study as inhibitors of
      phosphodiesterases and as inhibitors of blood platelet aggregation.
AB  - This paper presents the synthesis of new indole, pyridazino[4,5-b]-indole, and
      pyridazino[4,5-a]indole analogs as well as a study of their "in vitro" activity
      as inhibitors of different phosphodiesterases isolated from dog cardiac tissue,
      dog aorta, and bovine platelets; the study of their activity as inhibitors of
      platelet aggregation in guinea pig whole blood, with ADP and arachidonic acid
      (AA) as pro-aggregants, is also included. The selected compounds 8-benzyloxy-3,4
      dihydro-1-(3,4,5-trimethoxy)benzylideneaminopyridazin o[4,5- b]indole 14g, and 8
      benzyloxy-4-[(3,4-dimethyl)pyrazolyl]pyridazino[4,5-b]indo le 20 present an
      interesting profile as potential inodilators, with a complementary, beneficial
      activity as inhibitors of the aggregation, activities which could possibly be
      related to the inhibition of the PDE's. Among the other compounds studied, 8
      benzyloxy-3,4-dihydro-1-[4-(methyl)piperazino]acetamidopyrida zino[4,5- b]indol-4
      one 16c and 8-benzyloxy-3,4-dihydro-1-[4-(2-
      methoxyphenyl)piperazino]acetamidopyridazino[4,5-b]indol-4-o ne 16f stood out as
      inhibitors of platelet aggregation, with a mechanism that could possibly be
      related to the AA cascade.

PMID- 8554458
TI  - Facile syntheses of C2-symmetrical HIV-1 protease inhibitors.
AB  - With the goal of obtaining inexpensive yet potent anti-AIDS drugs, simple
      inhibitors of HIV-1 protease were synthesised. The C2-symmetrical pseudopeptidic
      substrate analogues can be prepared as inhibitors for HIV-1 protease starting
      from symmetrical ketones 3a-d by a facile four-step synthesis. After bromination
      of 3a-d to alpha,alpha'-dibromoketones 4a-d, we synthesised the diamino compounds
      6a-c by Gabriel synthesis, which were then coupled with Z-valine to yield
      inhibitors including a central hydroxy group 8a-d a-i by azidation, reduction
      with LiAlH4 and coupling of the beta,beta'-diaminohydroxy compounds with
      appropriate peptides. The first set of compounds showed only weak inhibition
      whereas the latter reach Ki values of up to 3.0 microM.

PMID- 8554459
TI  - Synthesis of new 2-([(phenoxy or phenyl)acetyl]amino)benzoic acid derivatives as
      3 alpha-hydroxysteroid dehydrogenase inhibitors and potential antiinflammatory
      agents.
AB  - A number of 2-([(phenoxy or phenyl)acetyl]amino)benzoic acid derivatives were
      prepared in about 50% yield from (phenoxy or phenyl)acetyl chloride and
      anthranilic acid derivatives. All the compounds were tested as in vitro
      inhibitors of 3 alpha-hydroxysteroid dehydrogenase, since enzyme inhibition
      predicts potential antiinflammatory activity in vivo. The most active compounds 3
      l, m, s are about 3.5 times more active than acetylsalicylic acid (ASA). Activity
      is influenced by electronic as well as steric effects.

PMID- 8554460
TI  - 4-(4-Guanidinobenzoyl)-2-imidazolones and related compounds: phosphodiesterase
      inhibitors and novel cardiotonics with combined histamine H2 receptor agonist and
      PDE III inhibitor activity.
AB  - A series of new positive inotropic agents was synthesized with the aim of
      combining the pharmacophores of the imidazolone-type phosphodiesterase (PDE)
      inhibitor enoximone and guanidine-type histamine H2 receptor agonists such as
      arpromidine. All compounds are para-substituted 4-benzoyl-5-alkyl-2-imidazolones.
      H2 agonism was incorporated by p-(hetero)arylalkyl substituents, in particular by
      an imidazolylpropyl guanidine group. In addition analogous ureas,
      cyanoguanidines, alkyl guanidine carboxylates, and amides were prepared. These
      functional groups were either directly attached to the phenyl ring or linked by
      an appropriate spacer. The compounds were screened for positive inotropic
      activity in the isolated electrically stimulated guinea pig papillary muscle and
      for inhibition of PDE III (cGMP-inhibited cAMP PDE, isolated from guinea pig
      heart). The cardiotonics obtained proved to be either PDE III inhibitors, some of
      them surmounting up to 3-fold the potency of enoximone, or pharmacological
      hybrids combining both PDE III inhibitor and histamine H2 receptor agonist
      activities. These hybrids were the most potent positive inotropic substances at
      the papillary muscle, probably due to their synergistic mechanism of action. The
      participation of histamine H2 receptors could be demonstrated in the papillary
      muscle preparation by pretreatment with the H2 antagonist famotidine (10 microM)
      as well as by further pharmacological experiments using isolated perfused hearts
      of guinea pigs and rats, isolated guinea pig right atria, adenylyl cyclase and H2
      receptor binding assays. At equieffective concentrations the moderate PDE III
      inhibitor and histamine H2 agonist N1-(4-[(1,3-dihydro-5-methyl-2-oxo-3H-imidazol
      4-yl)-carbonyl]phenyl)-N2 - [3-(1H-imidazol-4-yl)propyl]guanidine 65 and the 5
      ethyl homologue 66 were about 2 and 10 times more potent than enoximone at the
      papillary muscle. Moreover, both compounds produced a 2.5-fold higher maximal
      response than the reference compound.

PMID- 8554461
TI  - Anti-elastase and anti-hyaluronidase activities of saponins and sapogenins from
      Hedera helix, Aesculus hippocastanum, and Ruscus aculeatus: factors contributing
      to their efficacy in the treatment of venous insufficiency.
AB  - Triterpene and steroid saponins and sapogenins of medicinal plants (Aesculus
      hippocastanum L., Hedera helix L., Ruscus aculeatus L.) are claimed to be
      effective for the treatment/prevention of venous insufficiency. In this work we
      evaluated the inhibitory effects of these plant constituents on the activity of
      elastase and hyaluronidase, the enzyme systems involved in the turnover of the
      main components of the perivascular amorphous substance. The results evidence
      that for Hedera helix L., the sapogenins only non-competitively inhibit
      hyaluronidase activity in a dose-dependent fashion, showing comparable IC50
      values (hederagenin IC50 = 280.4 microM; oleanolic acid IC50 = 300.2 microM);
      both the saponins hederacoside C and alpha-hederin are very weak inhibitors. The
      same behaviour is observed for serine protease porcine pancreatic elastase: the
      glycosides are devoid of inhibitory action, while genins are potent competitive
      inhibitors (oleanolic acid IC50 = 5.1 microM; hederagenin IC50 = 40.6 microM).
      Constituents from Aesculus hippocastanum L. show inhibitory effects only on
      hyaluronidase, and this activity is mainly linked to the saponin escin (IC50 =
      149.9 microM), less to its genin escinol (IC50 = 1.65 mM). By contrast,
      ruscogenins from Ruscus aculeatus L., ineffective on hyaluronidase activity,
      exhibit remarkable anti-elastase activity (IC50 = 119.9 microM; competitive
      inhibition). The mechanism of elastase inhibition by triterpene and steroid
      aglycones, with a nitroanilide derivative as substrate, is discussed.

PMID- 8554462
TI  - Distribution behaviour of 131-iodine labelled trans-N,N'-bis-(ethoxy-carbonyl)-N
      [4-(3-iodo-4-methoxyphenyl)butyl]-N' -5- phenylpentyl)-1,4
      cyclohexanedimethanamine.
AB  - The title compound 9, which is a prodrug, and its active metabolite 7 were
      labelled with 131I (7*/9*) to investigate their pharmacokinetic behaviour,
      including the distribution between stomach, gut, muscle, blood, lung, liver,
      kidney, adrenal gland, heart, and spleen. Four hours after oral administration of
      7* to mice only 3% of the dose had been absorbed from the g.i. tract. After 24 h
      54% of the radioactivity still is found the gut, predominantly in the small
      intestine. These results explain why 7, which is a potent antiplatelet drug in
      vitro, shows no antithrombotic effect in vivo. In contrast, the produg 9/9* is
      absorbed considerably, i.e. up to 50% in 4 h from the g.i. tract depending on the
      dose applied and the vehicle used. At doses in the micromolar range the
      absorption appears to be diffusion limited. The highest concentrations are found
      in the liver and the kidneys suggesting a first pass effect of 7 followed by
      renal excretion. From the blood levels achieved, the dose necessary for an
      antithrombotic effect has been calculated to be about 100 mg/kg. In summary, the
      N-ethoxycarbonyl derivatives of oligoamines appear to be suitable prodrugs for
      oral administration of oligoamines.

PMID- 8554463
TI  - Cost-effectiveness of routine screening for proximal deep venous thrombosis in
      acquired brain injury patients admitted to rehabilitation.
AB  - OBJECTIVE: Determine the prevalence of proximal deep venous thrombosis (DVT)
      among acquired brain injury patients on admission to rehabilitation and assess
      cost-effectiveness of routine ultrasound screening for proximal DVT in those
      patients. DESIGN: Prospective study, sequential case series. SETTING: University
      tertiary care rehabilitation center. DATA SET: One hundred sixteen traumatic
      brain injury patients (TBI) and 48 nontraumatic brain injury patients were
      admitted to our brain injury (BI) unit over a 21-month period and screened for a
      DVT on admission to rehabilitation utilizing real time, Doppler, and color
      Doppler ultrasound. Patients with a previous clinically recognized and treated
      DVT were excluded. No patients had been treated with prophylactic anticoagulation
      or intermittent anticoagulation since their BI and all patients were within 4
      months of the original injury. RESULTS: Fourteen patients in total (8.5%) were
      found to have a DVT in the thigh or popliteal area, 9 of the 116 patients in the
      TBI group (7.8%), and 5 of the 48 patients in the nontraumatic BI group (10.4%).
      Statistically, there was no significant difference in the total number of
      detected proximal lower extremity DVTs between the TBI and the nontraumatic BI
      groups (Fisher's exact test). In the TBI group 22 patients had associated lower
      extremity or pelvic fractures, but this factor appeared not to be significant,
      because only 1 of the 22 patients was discovered to have a DVT. The average
      admission Glascow Coma Score (GCS) of the TBI group was 8.6 but there was no
      correlation with the GCS and prevalence of DVT. The additional cost of screening
      for and treating the additional DVTs utilizing color Doppler ultrasound is
      conservatively estimated to be $674.84 per patient admitted to the BI
      rehabilitation unit. It can be estimated the cost of saving one life is
      $129,527.83. CONCLUSION: DVT screening in this patient population appears to be
      more cost-effective than mass screening programs for either breast cancer or
      colorectal cancer. The cost per year of life saved, estimated at only $2,977.65
      ($129,527.83/43.5 years) for DVT screening for brain injury patients on admission
      to rehabilitation, is lower than those costs proposed for comparable programs
      with significant social support.

PMID- 8554464
TI  - Predicting discharge destination of stroke patients using a mathematical model
      based on six items from the Functional Independence Measure.
AB  - OBJECTIVE: A mathematical model using selected items from the Functional
      Independence Measure (FIM) was developed to predict disposition of stroke
      patients from an acute care hospital. DESIGN: Case series of 279 acute stroke
      patients admitted to the hospital from 4/91 through 12/93. Data collection
      remains ongoing; a second series of patients will be analyzed to validate results
      and determine if the same 6 FIM items are significant. SETTING: Tertiary care
      center, general acute care community hospital. PATIENTS: Diagnosis of acute
      stroke; 298 patients whose attending physician referred the patient to the
      rehabilitation team. An 18-item FIM was administered within 3 days of admission
      and 24 hours of discharge. MAIN OUTCOME MEASURE: FIM scores were analyzed to
      determine if the initial score could be used to predict disposition. Discriminant
      analysis identified 6 items as being statistically significant in predicting
      discharge to home, rehabilitation facility, or nursing home. Patient's actual
      discharge location was compared with the location predicted by the model
      developed using the FIM. RESULTS: Bathing, bowel, toileting, social interaction,
      dressing lower body, and eating were the selected initial FIM items that
      predicted disposition with 70% accuracy in our patient series. CONCLUSION: The
      FIM is effective in the acute care setting to help determine appropriate
      discharge status, with certain variables being more predictive than others.

PMID- 8554465
TI  - Acute and subacute rehabilitation.

PMID- 8554466
TI  - Statistical guidelines.

PMID- 8554467
TI  - Visual influence on contact pressure of hemiplegic patients through photoelastic
      sole image.
AB  - OBJECTIVES: To assess the visual influence through photoelastic sole image on
      upright posture in hemiplegic patients. DESIGN: Before-during trial. SETTING: An
      academically based rehabilitation setting. PATIENTS: Nineteen hemiplegic patients
      3 to 8 months after the stroke were designated as severe (n = 5), moderate I (n =
      4), moderate II (n = 5), and mild groups (n = 5). The severe, moderate, and mild
      groups were in Brunnstrom's motor recovery stage II, IV, and V, respectively.
      Vibration sense in the paretic leg was intact in the moderate II and mild groups,
      but impaired in the severe and moderate I groups. INTERVENTION: Visual feedback
      therapy on standing before before and while watching his or her own photoelastic
      sole image on a television screen (before vs during). MAIN OUTCOME MEASURE: The
      body-weight-bearing ratio on the paretic sole was analyzed. RESULTS: The body
      weight-bearing ratio on the paretic sole increased during visual feedback (before
      vs during, percentage, severe, 21.8 +/- 11.4 vs 38.7 +/- 13.7, p < .02; moderate
      I, 30.4 +/- 11.1 vs 39.3 +/- 6.4, not significant; moderate II, 32.8 +/- 10.3 vs
      46.8 +/- 7.8, p < .05; mild, 29.7 +/- 7.0 vs 41.8 +/- 7.5, p < .005; mean +/-
      SD). CONCLUSION: As the only difference between the moderate I and II groups was
      impaired or intact vibration sense in the paretic limbs, vibration sense along
      with motor recovery is an important factor to increase body weight loading on the
      paretic sole in hemiplegic patients.

PMID- 8554468
TI  - Peroneal stimulator; evaluation for the correction of spastic drop foot in
      hemiplegia.
AB  - OBJECTIVE: The objective of the study was to assess the orthotic and therapeutic
      value of the peroneal stimulator (PS) for adult hemiplegic patients. DESIGN: This
      was a two-period crossover study lasting 11 weeks. After recruitment each patient
      had a 4-week control period followed by a 4-week treatment period. The patients
      were assessed before the control period, after the control period, and after the
      treatment period. SETTING: Nineteen patients were recruited from physiotherapy
      departments in the Glasgow area; 2 subsequently dropped out before the treatment
      period. PATIENTS: All patients had hemiplegia as a result of cerebrovascular
      accident (CVA) and were greater than 3 months but less than 36 months post-CVA.
      Average time since stroke was 7 months. MAIN OUTCOME MEASURES: The patients' gait
      was assessed over smooth linoleum, carpet, and uneven ground. Gait was evaluated
      using a switch-based portable system. Outcome measures were the temporal gait
      parameters of speed, symmetry, heel strike, and foot inversion during stance. The
      gait evaluation was repeated on 5 separate days at each assessment. The Barthel
      Index was applied to each session. RESULTS: There was a significant orthotic
      improvement in inversion on all surfaces and for symmetry on linoleum (AN-OVA, p
      = .05). There was no significant improvement in patients' gait when not using the
      PS. There was a significant improvement in the Barthel Index over the treatment
      period (Wilcoxon, p = .05). CONCLUSION: Use of the PS an an orthotic device late
      in the rehabilitation program would be appropriate for a selected subpopulation
      of patients.

PMID- 8554469
TI  - Ipsilateral pushing in stroke: incidence, relation to neuropsychological
      symptoms, and impact on rehabilitation. The Copenhagen Stroke Study.
AB  - OBJECTIVES: A "pusher syndrome" encompassing postural imbalance and hemineglect
      is believed to aggravate the prognosis of stroke patients. Our aim was to
      determine the incidence, associated neuropsychological symptoms, and the
      consequences for rehabilitation of ipsilateral pushing. DESIGN: Consecutive and
      community-based. SETTING: A stroke unit receiving all acute stroke patients from
      a well-defined catchment area. All stages of rehabilitation were complete within
      the unit. PATIENTS: 647 acute stroke patients admitted during a 1-year period.
      Excluded were 320 patients who did not receive physiotherapy because they did not
      have pareses of the leg, had a fast remission, or died. MAIN OUTCOME MEASURES:
      Gain in activities of daily living (ADL) function (Barthel Index), time course of
      functional remission, and discharge rate to nursing home. The independent impact
      of ipsilateral pushing was analyzed with multiple linear and logistic regression
      analyses. RESULTS: Ipsilateral pushing was found in 10% of the included patients.
      No significant differences were found in the incidence of hemineglect and
      anosognosia between patients with and without ipsilateral pushing. No association
      with side of stroke lesion was found. Ipsilateral pushing had no independent
      influence on gain in ADL function or discharge rate to nursing home, but patients
      with ipsilateral pushing used 3.6 weeks (p < .0001) more to reach the same final
      outcome level than did patients without ipsilateral pushing. CONCLUSIONS: The
      existence of a "pusher syndrome" was not confirmed. Ipsilateral pushing did not
      affect functional outcome, but slowed the process of recovery considerably.

PMID- 8554470
TI  - Obstructive and restrictive pulmonary dysfunction increases disability in
      Parkinson disease.
AB  - OBJECTIVE: The purpose of this study was to determine in Parkinson disease the
      impact of pulmonary dysfunction on daily living activities (DLA). PATIENTS:
      Extrapyramidal motor impairment, pulmonary dysfunction, and DLA disabilities were
      studied in 58 Parkinson patients consecutively enrolled in a rehabilitation
      service at a university hospital. MAIN OUTCOME MEASURES: Extrapyramidal motor
      impairments were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS)
      and the DLA disabilities by the UPDRS, Hoehn-Yahr, and Schwab-England scales. The
      pulmonary dysfunctions were assessed by spirometry with flow-volume loops, body
      plethysmography with lung volumes computation, and maximal inspiratory and
      expiratory static mouth pressures. RESULTS: Parkinson patients showed important
      modifications of pulmonary function with a decrease in forced vital capacity,
      forced expiratory volume in the first minute, and arterial PO2, and an increase
      in residual volume and total airway resistance (RAW). In addition, they showed a
      high incidence of airway ventilatory obstructions and restrictive dysfunction.
      The impact of lung disease on daily living activities in Parkinson disease
      patients was higher in subjects with restrictive pulmonary dysfunctions (Schwab
      England test and turning in bed and adjusting bedclothes, walking, falling, and
      freezing when walking items of UPDRS) and airway obstructions (handling utensils,
      dressing and hygiene items of UPDRS). CONCLUSIONS: Airway obstructions or
      restrictive pulmonary dysfunctions present a high prevalence in Parkinson
      disease, contributing as a main factor for DLA dysfunctions. The evaluation and
      rehabilitation of respiratory disturbances should be systematically included in
      the management of these patients.

PMID- 8554471
TI  - Intrathecal baclofen administration for control of severe spinal spasticity:
      functional improvement and long-term follow-up.
AB  - OBJECTIVES: To assess long-term efficacy and functional benefits of intrathecal
      baclofen for severe spinal spasticity. DESIGN: A prospective before-after trial.
      SETTING: A neurological rehabilitation department of a university hospital. Pump
      implantation was realized in neurosurgery; follow-up was carried out mostly on an
      outpatient basis. PATIENTS: Eighteen patients with severe and disabling spinal
      spasticity received intrathecal baclofen by an implantable pump; average follow
      up was 37.4 months (range, 9 to 72). MAIN OUTCOME MEASURES: Spasticity (Ashworth
      and spasms frequency scores); disability (Functional Independence Measure [FIM]).
      RESULTS: A significant decrease in tone and spasms was observed in all patients.
      Tolerance appeared during the first 6 to 9 months. Later on, efficacy remained
      stable, except in cases of mechanical problems of the pump or catheter.
      Functional assessment found a highly significant (p < .001) increase of FIM score
      (particularly for bathing, dressing lower body, transfers, and in some cases,
      locomotion). This was particularly marked in patients with thoracic spinal cord
      lesion. In cases of severe upper limb dysfunction, FIM was only improved for
      wheelchair displacements, due to a better sitting position, but nursing became
      easier and life comfort was enhanced. Severe side effects (overdose) were
      observed in two cases. CONCLUSION: Efficacy remained stable after 6 to 9 months.
      Marked improvement of functional independence was observed in paraplegic
      patients. Improvement was less spectacular in patients with severe upper limb
      dysfunction, but nevertheless appreciable in terms of life comfort and use of
      attendants.

PMID- 8554472
TI  - Posture effect on seating interface biomechanics: comparison between two seating
      cushions.
AB  - OBJECTIVE: This study aimed at investigating the effects of sitting posture on
      ischial pressure and pelvic orientation for two types of cushions. DESIGN: Two
      types of seating devices, Roho and Polyurethane (PU) Foam cushions, six
      predefined postures, and two subject groups, Normal and Paraplegic, were tested.
      Ischial pressure and pelvic orientation were monitored. The sequence in which the
      cushions were tested were randomized, and the postures were tested according to a
      preplanned sequence. SETTING: The experiments were carried out in the laboratory
      of a rehabilitation engineering centre in Hong Kong. PARTICIPANTS: Six paraplegic
      subjects (referred sample) and 8 normal volunteers were tested. At the time of
      study, no subjects showed any signs of pressure sore or other health problems.
      MAIN OUTCOME MEASURES: It was hypothesized that sitting posture could
      significantly affect pelvic orientation as well as pressure distribution. It was
      also hypothesized that cushion selection was a critical factor in compensating
      the adverse effects of postures on pressure distribution. RESULTS: With the
      paraplegic group, the maximum ischial pressure recorded on Roho for various
      postures ranged from 88 mmHg for the Trunk-Bent-Forward (PF) posture to 146 mmHg
      for the Trunk-Bent-Right (PR) posture, whereas on PU foam cushions, the values
      ranged from 106 mmHg for the PF posture to 221 mmHg for the PR posture. With the
      paraplegic subjects sitting with their trunks bent laterally, it was found that
      the mean pressure difference between the left and right ischial tuberosities was
      more prominent on the PU foam cushion than on the Roho. CONCLUSION: Sitting
      posture can significantly affect pelvic orientation and ischial pressure. This
      study was also showed that the Roho cushion was significantly more efficient in
      compensating the adverse effects of sitting posture on pressure distribution.

PMID- 8554473
TI  - Traumatic cervical spinal cord injury: relation between somatosensory evoked
      potentials, neurological deficit, and hand function.
AB  - OBJECTIVE: Median and ulnar somatosensory evoked potentials (SEP) in the
      assessment of cervical spinal cord injury (SCI) in relation to the outcome of
      hand function. DESIGN: Cohort analytical study. SETTING: Spinal cord injury
      center, university hospital. PATIENTS: Consecutively sampled, 23 acute and 46
      chronic tetraplegics. MAIN OUTCOME MEASURES: (1) Median and ulnar SEP recordings
      graded in 5 categories, from normal to absent; (2) clinical examination of
      algesia/aesthesia in dermatomes C5/6 and C8/Th1 graded in categories of normal,
      impaired, and loss of sensation; (3) clinical examination of hand function graded
      in 4 categories, from active to inactive hand function. RESULTS: Pathological
      median and ulnar SEP were found in 46% and 76% of patients, respectively. A
      differentiation between upper (C3-C6) and lower (C6/C7-Th1) cervical SCI was
      possible by comparing the SEP N20 latencies (but not amplitudes) of both nerves
      (Mann-Whitney U test, p < .01). In follow-up examinations over 6 months the N20
      amplitude increased significantly (ANCOVA, p < .001), while the N20 latency did
      not change. By both ulnar SEP recordings and assessment of the sensory deficit in
      dermatome C8/Th1 the outcome of hand function, i.e., the development of active or
      inactive hand function, could be predicted (Mann-Whitney U test, p < .01).
      CONCLUSION: Median and ulnar SEP are valuable to indicate the level of injury,
      the degree of sensory impairment and to predict the outcome of hand function even
      in unconscious patients. They can improve the diagnostic assessment of cervical
      SCI.

PMID- 8554474
TI  - Functional outcome following rehabilitation of the cancer patient.
AB  - OBJECTIVE: To identify impairments resulting from cancer or its treatment in
      patients undergoing inpatient rehabilitation, to assess the extent of functional
      gains, and to determine if cancer type, ongoing radiation treatment, or the
      presence of metastatic disease influences functional improvement. DESIGN AND
      SETTING: A retrospective, case series of cancer patients undergoing inpatient
      rehabilitation at a free-standing, university-affiliated rehabilitation hospital.
      PARTICIPANTS: A referred sample of 159 patients admitted because of functional
      impairments resulting from cancer or its treatment during a 2-year time period.
      INTERVENTION: Comprehensive inpatient rehabilitation. MAIN OUTCOME MEASURE:
      Functional status as measured by the motor score of the Functional Independence
      Measure. RESULTS: Significant functional gains were made between admission (mean
      = 42.9) and discharge (mean = 56.0; p < .001), with all cancer subgroups making
      similar gains. The presence of metastatic disease did not influence functional
      outcome, and those patients receiving radiation actually made larger functional
      improvements (p = .025). CONCLUSION: Individuals impaired by cancer or its
      treatment benefit from inpatient rehabilitation. The presence of metastatic
      disease or ongoing radiation should not preclude participation.

PMID- 8554475
TI  - Rehabilitation after hip fracture--equal opportunity for all?
AB  - OBJECTIVES: To determine whether factors unrelated to clinical appropriateness
      affect use of physical and occupational therapy (PT/OT) in elderly Medicare
      patients with acute hip fracture. DESIGN: Bivariate and multivariate analysis of
      detailed clinical data retrospectively gathered from medical records and of
      nonclinical variables obtained through linkage with the American Hospital
      Association data base. SETTING: 297 randomly selected hospitals from 5 states.
      PATIENTS: 2,762 elderly Medicare patients hospitalized with a primary diagnosis
      of acute hip fracture who were hospitalized during 1981-1982 or 1985-1986.
      INTERVENTION: Observational study. MAIN OUTCOME MEASURES: Initiation and
      intensity of PT/OT while in the acute hospital. RESULTS: We found evidence that
      factors not relevant to clinical appropriateness, such as race, hospital size,
      and state, significantly affect whether patients receive any PT/OT after acute
      fracture, as well as the intensity of PT/OT. For example, after controlling for
      patient clinical characteristics, we found that 63% of African-American patients
      received low-intensity PT/OT in comparison to 43% among non-African-American, and
      we found threefold differences among states both in initiation of PT/OT and in
      the intensity of its use. Overall, clinical characteristics had relatively
      greater influence on whether patients started PT/OT, whereas factors not relevant
      to clinical appropriateness had relatively greater influence on how much
      rehabilitation was provided. CONCLUSION: There are significant disparities in use
      of rehabilitation after hip fracture, only partially explained by patient
      clinical characteristics. Factors without obvious relevance to the clinical
      appropriateness of PT/OT exert a significant influence on use of rehabilitation
      services, particularly on the intensity of their use.

PMID- 8554476
TI  - Methylphenidate effect on attention deficit in the acutely brain-injured adult.
AB  - OBJECTIVES: To determine the efficacy of methylphenidate in improving attention
      and functional outcome in acutely brain-injured adults. DESIGN: Prospective
      multiple baseline design (A-A-B-A) utilized on a consecutive sample of patients.
      SETTING: Acute brain injury rehabilitation unit in a large academic medical
      center. PATIENTS: Eleven acutely brain-injured adults were included by performing
      below two standard deviations of the age equivalent norms on 4 of 5
      neuropsychological tests for attentional capacity. One subject was withdrawn
      after developing tachycardia. INTERVENTION: After a 1-week baseline assessment,
      subjects were placed on increasing doses of methylphenidate (Ritalin) so that on
      Day 7 all patients received a dose of 15 mg at 8 am and 12 pm. MAIN OUTCOME
      MEASURES: Nine neuropsychological subtests measured attention on admission, at 1
      week, while on methylphenidate, and 1 week after its discontinuation. Functional
      outcome was evaluated utilizing the Disability Rating Scale (DRS) at the same
      intervals. RESULTS: Digit Span, Mental Control, and Symbol Search scores improved
      significantly (p < .05) on methylphenidate (A-B) as compared with the pre
      methylphenidate (A-A) period. This advantage remained when the drug was removed.
      The mean improvement in DRS scores on methylphenidate approached a significant
      difference (p < .06) from that change in the DRS scores between baseline 1 and 2.
      CONCLUSIONS: Use of methylphenidate in acutely brain-injured adults was well
      tolerated and demonstrated a significant improvement in attention compared to
      natural recovery in a rehabilitation setting. Methylphenidate also correlated
      with faster functional recovery as measured by the Disability Rating Scale
      although the improvement did not achieve statistical significance.

PMID- 8554478
TI  - Metabolic evaluation of the criteria used to fit elbow crutches by measurement of
      oxygen consumption.
AB  - OBJECTIVE: To investigate if elbow crutches fitted using conventional guidelines
      are the most metabolically efficient. DESIGN: Repeated measure connivance sample
      using crutch length as the independent variable. SETTING: A university exercise
      physiology laboratory. OTHER PARTICIPANT: Connivance sample of 10 students free
      from cardiovascular disease, with previous experience in crutch ambulation, and
      between heights of 160 and 175 cm. Four potential subjects refused to participate
      in the study. INTERVENTIONS: Crutch length was adjusted using conventional
      guidelines, and to lengths 2.5 cm above and below this setting. Oxygen
      consumption was measured using indirect open-circuit spirometry during the final
      3 minutes of ambulation using self-selected walking speeds. MAIN OUTCOME MEASURE:
      Crutches adjusted to the convention setting are not the most efficient in terms
      of metabolic energy expenditures. RESULTS: A significant reduction in oxygen rate
      (p = .012), oxygen cost (p = .010), and respiratory exchange ratio (p = .009)
      were observed when comparing crutches adjusted to -2.5 cm of the standard height
      with conventional crutch height. Crutches adjusted 2.5 cm above the standard
      height also required less energy, but these values failed to reach any
      statistical significance (p > .05). CONCLUSION: The importance of fitting
      crutches to the correct length using conventional guidelines has not been
      substantiated in this study. Clinically, there should be a move away from
      adherence to crutch-fitting criteria and more incorporation of patient feedback
      to fit crutches to the optimal height. Future research should evaluate the
      reliability of practical clinical measures such as heart rate and perceived
      exertion to fit crutches to the optimal height.

PMID- 8554477
TI  - Aerobic walking in slowly progressive neuromuscular disease: effect of a 12-week
      program.
AB  - OBJECTIVE: Poor cardiorespiratory endurance is a common finding in neuromuscular
      disease (NMD), and the capacity of such patients to respond to aerobic training
      is unclear. This study was conducted to determine if a 12-week walking program
      results in increased aerobic capacity in slowly progressive NMD subjects, whether
      such a program is safely tolerated, and whether such patients can adhere to a
      self-monitored, home-based training program. DESIGN: Before-after trial. SETTING:
      Subjects' homes. PATIENTS: A cohort of 8 slowly progressive NMD subjects (4 men,
      4 women) followed in the neuromuscular disease clinic participated (age, 36.6 +/-
      8.0 yrs; ht, 170 +/- 11 cm; wt, 74.3 +/- 19.0 kg) (Mean +/- SD). INTERVENTION:
      Subjects walked 15 to 30 min 3 to 4 days a week at 50% to 60% of their heart rate
      reserve. MAIN OUTCOME MEASURES: Resting, submaximal, and peak heart rates,
      systolic and diastolic blood pressures, oxygen uptake, and peak power output.
      RESULTS: Graded exercise testing to volitional fatigue using a semirecumbent
      cycle ergometer before and after the training program found significant decreases
      in submaximal heart rate by 7 +/- 3 beats/min (Mean +/- SEM) (95% CI = -23 to 9)
      (p = .046) and submaximal systolic blood pressure by 11 +/- 4 mmHg (95% CI = -31
      to 9) (p = .019), and nonsignificant increases in peak power output and VO2.
      CONCLUSIONS: These results suggest that moderate-intensity aerobic exercise
      training is well tolerated and may provide modest improvement in aerobic capacity
      in slowly progressive NMD subjects.

PMID- 8554479
TI  - Lumbar trunk muscle endurance testing: an inexpensive alternative to a machine
      for evaluation.
AB  - OBJECTIVES: The goals of this study were to verify the reliability and safety of
      new methods for evaluating trunk muscle endurance, and to compare the differences
      between healthy subjects and patients with chronic low-back pain. DESIGN:
      Randomized and controlled study. SETTING: A referral center and institutional
      practice, and outpatient care. SUBJECTS: Ninety healthy subjects (37 men and 53
      women average age 46.2 years) and 100 patients with CLBP (40 men and 60 women;
      average age 45.3 years) participated in this study. MAIN OUTCOME MEASURES: During
      trunk flexor and extensor endurance tests, the subjects were asked to maintain
      the original positions for as long as possible. The performance time (seconds)
      for which subject could maintain the position was compared between two groups.
      Test-retest correlation (r) was also analyzed. The degree of lumbar lordosis was
      compared in conventional and new methods. RESULTS: All test-retest correlations
      were significantly high in both groups (p < .01). The performance time was much
      longer in the healthy subjects than in the patients with CLBP during any
      procedures (p < .01). Lumbar lordosis was significantly less in our method than
      in the Kraus-Weber test (p < .01). CONCLUSIONS: This study demonstrated that our
      methods for measuring trunk flexor and extensor endurance had high reliability,
      reproducibility, and safety, and were easy to perform, with no need for special
      equipment. This study also showed that trunk muscles in patients with CLBP were
      more easily fatigued, compared with those in healthy subjects.

PMID- 8554480
TI  - Improved arousal and initiation following tricyclic antidepressant use in severe
      brain injury.
AB  - Three patients with severe traumatic brain injury demonstrated significant
      improvement in arousal and initiation after administration of tricyclic
      antidepressants. The first patient showed improved motor and speech initiation in
      response to amitriptyline following several months of functional plateau. The
      second patient was minimally responsive 2 months after injury and demonstrated
      improved arousal following the use of desipramine. Both patients deteriorated
      when the medications were discontinued and improved again when they were
      restarted. These two cases provide strong evidence for a medication effect. The
      third patient began to verbalize following desipramine administration, despite
      being mute for more than a year after injury. Previous case reports describe
      cognitive-enhancing effects, such as improved arousal, attention, memory, and
      initiation, of dopaminergic agents, and in the case of tricyclic antidepressants,
      effects on agitation. The role of norepinephrine in promoting neurological
      recovery after brain lesions has been demonstrated in animals. The cases
      presented here provide some of the first data to show similar efficacy in humans
      and underscore the need for controlled trials to better determine which patients
      will benefit.

PMID- 8554481
TI  - Paraplegia following post-traumatic thoracic spinal stenosis: a case report.
AB  - Compromise of the spinal canal and its neural elements is a well-recognized
      pathological entity affecting the lumbar or cervical spine. Thoracic stenosis in
      the absence of a generalized rheumatological, orthopedic, or metabolic disorder
      is rare. The authors report a case of progressive thoracic myelopathy leading to
      paraplegia following severe thoracic spinal stenosis secondary to post-traumatic
      hypertrophy of thoracic laminae and ossification of the ligamentum flavum and
      posterior longitudinal ligament.

PMID- 8554482
TI  - Functional hand surgery following tetraplegia.
AB  - Traumatic tetraplegia is an overwhelming injury often requiring permanent
      adaptations by patients and families. The greatest potential for improving the
      quality of life lies with rehabilitation and restoration of upper extremity
      function. Reconstructive hand surgery following tetraplegia is individualized
      based on functional level and can significantly improve hand function and quality
      of life. Careful selection and evaluation of surgical candidates in combination
      with an experienced surgeon and hand rehabilitation team are critical for a
      successful outcome.

PMID- 8554484
TI  - [Academic cardiology and professional qualification in Brazil . Are we on the
      right path?].

PMID- 8554483
TI  - Physical medicine and rehabilitation workforce study: the supply of and demand
      for physiatrists.
AB  - OBJECTIVE: Analysis, results, and implications of a supply and demand workforce
      model for physical medicine and rehabilitation. Explicit issues addressed
      include: (1) the supply implications of maintaining current (1994-1995) output of
      physiatrists from residency programs; (2) the implications of continued growth in
      managed care on the demand for the services of physiatrists; (3) likely future
      supply and demand conditions; and (4) strategies to adapt to future conditions.
      DESIGN: A workforce model of the supply and demand for physiatrists was
      developed. Parameters of the model are estimated using econometric models and by
      applying the judgments of a consensus panel. The model evaluated several
      different scenarios regarding managed care growth, competition from other
      providers and other factors. RESULTS: Based on the analysis, physiatrists will
      continue to be in excess demand through the year 2000. More aggressive growth in
      managed care can affect this result. CONCLUSIONS: Based on an overall assessment
      of supply and demand conditions, and under the assumption that the supply of new
      entrants each year remains in the range of 1994-1995 levels, demand for
      physiatrists will continue to exceed supply, on average, through the year 2000.
      Excess supply has, and will, emerge in selected geographic areas. If the
      profession is successful in informing the market regarding the advantages of
      physiatry, the profession can continue to grow without experiencing excess
      supply, in the aggregate, for the foreseeable future.

PMID- 8554485
TI  - [Pulse pressure. Its importance in geriatric cardiology].

PMID- 8554486
TI  - [Diagnosis of infective endocarditis].

PMID- 8554487
TI  - [Role of circumflex coronary artery involvement in non-Q wave myocardial
      infarction].
AB  - PURPOSE: To determine the patency and incidence rates of left circumflex coronary
      artery (LCX) as the infarct related artery (IRA) in Q-wave and non-Q wave acute
      myocardial infarction (AMI). METHODS: Two-hundreds and twenty one patients (172
      men) with AMI were stratified in Q and non-Q waves groups. All patients were
      submitted to cinecoronary angiography 72 hours after the beginning of symptoms
      and the IRA and its patency were evaluated. RESULTS: In non-Q wave AMI, the LCX
      was considered to be the IRA in 35% of the patients. In Q wave AMI, this
      incidence was 8% (p < 0.001). Occlusion of LCX was seen in all non-Q wave AMI
      patients when it was the IRA. CONCLUSION: The incidence of LCX as IRA was
      significantly higher in non-Q wave AMI patients. This group did not have the
      previously expected greater patency rates, what could result in different
      clinical and evolutive characteristics.

PMID- 8554488
TI  - [Diagnostic value of echocardiography with dipyridamole in coronary disease and
      evaluation of its prognostic potentiality face to ergometry, plane dipyridamole
      Tc99m-MIBI myocardial perfusion scintigraphy and coronary cineangiography].
AB  - PURPOSE: To assess in a consecutive series of patients, the diagnostic accuracy
      of dipyridamole echocardiography and to compare its prognostic power with that
      from other tests. METHODS: Seventy eight patients prospectively were underwent to
      dipyridamole echocardiography (DET) and coronary arteriography for diagnostic and
      post-infarction investigation. The majority was underwent to treadmill stress
      test and Tc99MIBI-dipyridamole planar myocardial scintigraphy. Eleven variables
      with possible prognostic importance were analyzed in a stepwise model to identify
      independent predictors of events. RESULTS: Sensitivity and specificity for the
      presence of coronary artery disease (in non-M patients) and multivessel disease
      (in post-MI patients) were, respectively, 44%, 91%, 53% and 88%. Mean follow-up
      was 21 +/- 9 months, during which there were four deaths, four unstable angina
      episodes, four nonfatal myocardial infarctions and eight revascularization
      procedures. By multivariate analysis, the only independent predictor of events
      was the change in wall motion score index from rest to peak stress. CONCLUSION:
      DET is a valuable alternative to exercise stress test and myocardial perfusion
      scintigraphy. Semiquantitative estimation of ischemic area during pharmacological
      stress is an important prognostic marker.

PMID- 8554489
TI  - [Etiology of left bundle branch block in Porto Alegre].
AB  - PURPOSE: To determine the type of cardiac disease causing left bundle branch
      block (LBBB) in Porto Alegre, Brazil, and to assess the role of associated left
      axis deviation (-30 degrees or more in the frontal plane) in order to identify a
      specific etiology of LBBB. METHODS: Through reports from the assistant physicians
      or through examination of the patients, the underlying heart disease in 264 cases
      of LBBB was assessed. The chi-square test was used to determine a possible
      association between left anterior hemiblock LBBB and one or more specific type of
      underlying heart disease. RESULTS: Systemic arterial hypertension (30.7%),
      ischemic heart disease (30.3%), valvar heart disease (8.7%), cardiomyopathies
      (7.5%), idiopathic degenerative disease of the conduction system (1.6%) and
      miscellaneous heart diseases (1.2%) were the underlying heart diseases. The
      presence of LBBB did not indicate any specific type of cardiac disease.
      CONCLUSION: The causes of LBBB in Porto Alegre are the same as reported in the
      international medical literature. Upward and leftward deviation (> or = -30
      degrees) of QRS axis in the frontal plane did not show statistical significant
      association with any type of underlying cardiac disease.

PMID- 8554490
TI  - [Coronary arteriosclerosis and myocardial infarction in chronic Chagas' disease].
AB  - PURPOSE: To evaluate both the frequency of myocardial infarction and coronary
      atherosclerosis as well as the pathology of the later in necropsied chronic
      chagasic individuals. METHODS: Systematized gross and light microscopy were
      performed in hearts, especially at the three main coronary arteries. Eighty-nine
      hearts were studied, 35 chronic chagasics and 54 nonchagasics, all from males.
      Statistical tests were used for frequency analysis. RESULTS: Myocardial
      infarction occurred in 8.6% chagasics and in 7.4% nonchagasics. Coronary
      atherosclerosis was detected in 71.4% of chagasics and in 74.1% of nonchagasics.
      Its morphology was similar for both groups and indistinguishable from the
      classical descriptions of atherosclerosis. There were no cases showing lesions
      compatible with accelerated coronary atherosclerosis. CONCLUSION: The frequency
      of myocardial infarction and coronary atherosclerosis was the same for both
      chagasics and nonchagasic individuals. The morphological findings for the studied
      arteriopathy were identical for the two considered groups. However, it seems that
      the frequency of myocardial infarction is higher in chagasics with normal
      coronary arteries (with or without minimal atherosclerotic lesions), as compared
      with nonchagasics.

PMID- 8554492
TI  - [Prenatal echocardiographic study of septum primum redundancy and its
      relationship to the genesis of atrial extrasystole in the fetus].
AB  - PURPOSE: To test the hypothesis that the redundancy of the septum primum is more
      pronounced in fetuses with atrial premature beats than in normal fetuses.
      METHODS: Twenty-five consecutive fetuses with atrial premature beats detected by
      prenatal echocardiography as the sole alteration at a mean gestational age of 34
      +/- 3.3 (26 to 38) weeks and a mean maternal age of 27 +/- 6.5 (18 to 39) years
      made up the study group. The control group was formed by 50 consecutive fetuses
      without rhythm disturbances and normal prenatal echocardiography, examined at a
      mean gestational age of 33.9 +/- 3 (26 to 39) weeks and a mean maternal age of 31
      +/- 5.8 (18 to 43) years. A redundancy index (RI) was obtained as a ratio between
      the maximal septum primum excursion and the maximal left atrium diameter during
      atrial diastole, at the 4-chamber projection. Statistical analysis utilized the
      unpaired Student-Fisher's "t" test. RESULTS: The RI in the study group varied
      from 0.50 to 1.00 (mean = 0.758 +/- 0.127) and in the control group in ranged
      from 0.29 to 0.67 (mean = 0.449 +/- 0.080). These differences were statistically
      significant for p < 0.0001. CONCLUSION: Septum primum is more redundant in
      fetuses with atrial premature beats than in those with normal regular rhythm.
      Although it is still speculative that this feature may have a cause-effect
      relationship, the measurement of the RI during routine fetal echocardiography may
      allow detection of a potential risk factor FOR developing atrial arrhythmias.

PMID- 8554491
TI  - [Postoperative course of left ventricular function in aortic insufficiency].
AB  - PURPOSE: To analyze the follow-up of left ventricular function (LVF) after
      surgical correction of severe chronic aortic insufficiency (AI). METHODS: Twenty
      one out of 68 patients with AI, initially asymptomatic and that developed
      symptoms during the follow-up period of 24-36 months, were studied. Relationship
      between symptoms and LVF by echocardiogram and radioisotopic ventriculography at
      rest and in isotonic exercise were studied. Three clinical moments (CM) were
      assumed: CM-0- at the beginning of the study, when all patients were
      asymptomatic; CM-1- manifestation of the symptoms during 24-36 months; CM-2-
      corresponding to the late post-operative period of 8 months of 20 out of 21
      patients (one refused the surgery). The analysis did not show any significant
      differences between the mean values of all echocardiographic variables (diastolic
      and systolic diameters, shortening fraction, final systolic stress, volume-mass
      ratio, contractility index) and the ejection fraction of the left ventricle (EF)
      obtained by the radioisotope ventriculography at rest and, including exercise,
      between clinical moments 0 and 1. RESULTS: In the CM-2, involution was verified
      for functional class I/II in all cases and absence of expressive complications or
      immediate or late postoperative mortality. Comparison between CM-2 and 0 showed
      expressive regression of the diameters at rest in the postoperative period and
      with significant improvement in the means mainly the percentual variation of the
      EF and total time of effort. CONCLUSION: Symptoms assembled patients with more
      advanced eccentric hypertrophy and did not coincide with any immediate change in
      findings studied at rest and at exercise. It represented a point of reference for
      surgical indication compatible with late postoperative involution of chronic
      adaptation of AI.

PMID- 8554493
TI  - [Effect of diazepam on myocardial contraction and on the response to dopamine.
      Study in isolated rat hearts].
AB  - PURPOSE: The myocardial contractility variations and the cardiac rate were
      studied in isolated hearts of rats with injection of diazepam, dopamine and the
      association of both. METHODS: In all animals, after anesthesia, the hearts were
      removed and perfused with Krebs-Henseleit solution enriched by 95% O2 under a
      constant pressure of 90 cm H2O, until complete stabilization, for control value
      recordings. The following groups were studied: I) ten hearts: after stabilization
      the control values were recorded and dopamine (3 micrograms/ml) injected; IIA and
      IIB): also ten hearts were used and submitted to 50 micrograms and 100 micrograms
      of diazepam injections respectively. III) ten hearts studied with 50 micrograms
      of diazepam and 3 micrograms/ml of dopamine injection in a sequential form.
      RESULTS: Myocardial contractility arose in group I, from 37 g.seg-1 (control mean
      value) to 70 and 53 g.seg-1 (1st and 3rd min); p < 0.001. In the groups IIA and
      IIB the dT/dt fell considerably in relation to the control: 35 g.seg-1 to 24 and
      30 g.seg-1 (1st and 3rd min)--group IIA; p < 0.001 -32 g.seg-1 to 22 and 25 g.seg
      1 (1st and 3rd min)--group IIB; p < 0.001. In the group III, a partial inhibition
      of the inotropic effects of dopamine by the injection of diazepam was observed.
      Heart rate follows fully the dT/dt variations in the groups IIA, IIB and III.
      CONCLUSION: Diazepam presents inotropic and chronotropic negative effects with
      the 50 micrograms as well as with 100 micrograms injection and the chronotropic
      and inotropic effect of dopamine (3 micrograms) injection was partially inhibited
      by the previous injection (50 micrograms) of diazepam.

PMID- 8554494
TI  - [Postural changes during echocardiography. Is this manoeuver necessary in the
      differential diagnosis of fixed and free floating thrombus?].
AB  - A case of a 62 year-old woman with mitral stenosis and thrombosis of the left
      atrium diagnosed by two-dimensional echocardiography (2D-Echo) is reported.
      During the procedure, postural changes were performed and characterized the
      thrombus as floating one. The postural changes during 2D-echo examination allows
      differential diagnosis among fixed and free floating atrial thrombus. Such
      postural manoeuvres are also important in evaluating prognosis and therapeutic
      management of mitral stenosis.

PMID- 8554496
TI  - [Infective endocarditis. Importance of the echocardiogram].

PMID- 8554495
TI  - [A false diagnosis of hypertrophic myocardiopathy in pheochromocytoma].
AB  - A 24 year-old man was admitted with hypertensive crises and diagnosis hypothesis
      of neurofibromathosis and pheochromocytoma with blood pressure of 150 x 110mmHg
      and in use of anti-hypertensive drugs. The electrocardiogram (EKG) showed left
      ventricle hypertrophy. An echocardiogram showed interventricular septum (IVS)
      thickness of 16mm, posterior wall (PW) thickness of 11mm (ratio IVS/PW was 1.4).
      Diastolic ventricular diameter was 39mm with gradient of 52mmHg and mild mitral
      valve murmur by pulsate Doppler. Increased vanillylmandelic acid and
      metanephrines in a 24-hour sample of urine has confirmed diagnosis of
      pheochromocytoma within was localized by 131I metaiodobenzyl-guanidine scan and
      computerized axial tomography. The patient was submitted to right adrenalectomy.
      Blood pressure was normalized. Evaluation an year later revealed a healthy man
      with normal laboratory exams, EKG and echocardiogram. It seems that the
      hypertrophy was consequence of the hypertension and pheochromocytoma, was not
      hypertrophic cardiomyopathy.

PMID- 8554497
TI  - [Brazilian study with alteplase in acute myocardial infarction--EBRALT].
AB  - PURPOSE: Prospective evaluation of the effects of the intravenous administration
      of rt-PA (Alteplase) up to 6 hours after the pain onset on the patency of the AMI
      related artery, mortality, adverse reactions and complications. METHODS: Open,
      multicenter, non-comparative study involving 139 patients with diagnosis of AMI,
      with less than 6h of duration. The rt-PA was intravenously administered, in a
      dose of 100mg, as follows: 10mg in the 1st 2min, 50mg in 58min and 40mg in
      120min. In addition, the patients received intravenous heparin (5000 IU at first
      and then, 1000 IU/hour, for 24h), aspirin (500mg in the 1st day and then,
      100mg/day) and dipyridamole (75mg, three times a day), during the hospitalization
      period. The angiographic study was performed in 129 (93%) patients, within the
      1st week of AMI. RESULTS: The age of the patients ranged from 29 to 85 (mean 56.6
      +/- 10.3) years. The related artery for the AMI was patent (TIMI II and III flow)
      in 92/129 (71%) patients, with a mean ejection fraction of 50 +/- 14%, a value
      higher than that exhibited by patients with TIMI 0 and I flow (average ejection
      fraction = 44 +/- 14%). Reinfarction was diagnosed in 9 (6.4%) patients during
      the hospitalization period. During this period, there were 9 (6.4%) deaths. Minor
      hemorrhages were observed in 19 (12%) patients and major hemorrhages in 3 (2%)
      cases. No patient experienced stroke. CONCLUSION: The administration of the rt-PA
      therapy in the AMI was associated to a high reperfusion index of the related
      artery for the infarction, with improved left ventricular function and low
      incidence of reinfarction and in-hospital mortality, as well as, complications.

PMID- 8554498
TI  - [Comparative study of gemfibrozil versus pravastatin in the treatment of patients
      with coronary artery disease and low HDL cholesterol levels].
AB  - PURPOSE: To evaluate the effects of gemfibrozil and pravastatin in coronary
      artery disease patients with HDL-cholesterol (HDL-C) < 35 mg/dl). METHODS: Twenty
      nine patients (20 males, 60 +/- 9) were divided in a gemfibrozil group (G) (1200
      mg/day n = 15) and a pravastatin group (P) (10 or 20 mg n = 10 and 4,
      respectively). The plasma lipid profile (LP) e.g. total cholesterol (TC),
      fractions and triglycerides (TG) was determined at 4 and 12 weeks of treatment.
      RESULTS: HDL-C was not affected in P, TC and LDL-cholesterol (LDL-C) reductions
      were superior to those in G (31.3% vs 13.4% and 38.7 and 11.5%, p < 0.05 and <
      0.01 respectively). In G HDL-C raised by 50% (12th week p < 0.01). Gemfibrozil
      reduced TG levels in 44.7% while in P it varied -32.2% (12th week p < 0.01 and <
      0.05 respectively). CONCLUSION: Gemfibrozil is more effective in reducing TG and
      raising HDL-C than pravastatin. On the other hand, pravastatin was more potent in
      reducing LDL-C levels.

PMID- 8554499
TI  - [Anatomical characteristics of non-Q-wave infarction].

PMID- 8554500
TI  - [National Consensus on Ergometry. Department of Ergometry and Cardiovascular
      Rehabilitation of the Brazilian Cardiology Society].

PMID- 8554502
TI  - Phospholipase C delta 1 requires a pleckstrin homology domain for interaction
      with the plasma membrane.
AB  - The structural requirements of phospholipase C delta 1 for interaction with the
      plasma membrane were analysed by immunofluorescence after microinjection into
      living cells. Microinjection of deletion mutants revealed that the region
      required for membrane attachment and binding of inositol 1,4,5-trisphosphate in
      vitro corresponded to the pleckstrin homology domain, a structural module
      described in more than 90 proteins.

PMID- 8554503
TI  - Human papillomavirus type 6 E7 protein is a substrate in vitro of protein kinase
      C.
AB  - The E7 proteins of 'low-risk' and 'high-risk' human papillomaviruses (HPV) are
      phosphorylated by casein kinase II. In this study, we report that the 'low-risk'
      HPV 6 E7 protein, but not the 'high-risk' HPV 16 E7 protein, can be
      phosphorylated in vitro on threonine at amino acid position 7 by protein kinase
      C. This is the first example of a qualitative biochemical difference between the
      HPV 6 E7 and HPV 16 E7 proteins.

PMID- 8554504
TI  - Bacterial morphinone reductase is related to Old Yellow Enzyme.
AB  - Morphinone reductase, produced by Pseudomonas putida M10, catalyses the NADH
      dependent saturation of the carbon-carbon double bond of morphinone and
      codeinone, and is believed to be involved in the metabolism of morphine and
      codeine. The structural gene encoding morphinone reductase, designated morB, was
      cloned from Ps. putida M10 genomic DNA by the use of degenerate oligonucleotide
      probes based on elements of the amino acid sequence of the purified enzyme.
      Sequence analysis and structural characteristics indicated that morphinone
      reductase is related to the flavoprotein alpha/beta-barrel oxidoreductases, and
      is particularly similar to Old Yellow Enzyme of Saccharomyces spp. and the
      related oestrogen-binding protein of Candida albicans. Expressed sequence tags
      from several plant species show high homology to these enzymes, suggesting the
      presence of a family of enzymes conserved in plants and fungi. Although related
      bacterial proteins are known, morphinone reductase appears to be more similar to
      the eukaryotic proteins. Morphinone reductase was overexpressed in Escherichia
      coli, and has potential applications for the industrial preparation of
      semisynthetic opiates.

PMID- 8554505
TI  - Structure of the quinoprotein glucose dehydrogenase of Escherichia coli modelled
      on that of methanol dehydrogenase from Methylobacterium extorquens.
AB  - The structure of methanol dehydrogenase (MDH) at 0.194 nm (1.94 A) has been used
      to provide a model structure for part of a membrane quinoprotein glucose
      dehydrogenase (GDH). The basic superbarrel structure is retained, along with the
      tryptophan-docking motifs. The active-site regions are similar, but there are
      important differences, the most important being that GDH lacks the novel
      disulphide ring structure formed from adjacent cysteines in MDH; in GDH the
      equivalent region is occupied by His-262. Because of the overall similarities in
      the active-site region, the mechanism of action of GDH is likely to be similar to
      that of MDH. The differences in co-ordination to the cation and bonding to the
      pyrrolo-quinoline quinone (PQQ) in the active site may explain the relative ease
      of dissociation of the prosthetic group from the holo-GDH. There are considerable
      differences in the external loops, particularly those involved in formation of
      the shallow funnel leading to the active site, the configuration of which
      influences substrate specificity. The proposed model is consistent in many
      respects with previous proposals for the active-site structure based on the
      effects of chemical modification on binding of PQQ and enzymic activity.

PMID- 8554501
TI  - Transcriptional regulation of genes for ornithine cycle enzymes.

PMID- 8554506
TI  - Functional expression and characterization of the Trypanosoma brucei procyclic
      glucose transporter, THT2.
AB  - The gene encoding THT2, one of two hexose-transporter isoforms present in
      Trypanosoma brucei, has been expressed in both Xenopus laevis oocytes and a
      stably transfected line of Chinese hamster ovary (CHO) cells. The heterologously
      expressed gene encodes a protein with pharmacological and kinetic parameters
      similar to those of the hexose transporter measured in procyclic-culture-form
      trypanosomes. The substrate recognition of the THT2 transporter differed from
      that of the THT1 isoform, which is expressed only in bloodstream forms, in that:
      (i) it has a relatively high affinity for substrate with a Km of 59 microM for 2
      deoxy-D-glucose (2-DOG) and a similar high affinity for D-glucose (compared with
      Km of 0.5 mM for 2-DOG in bloodstream forms); (ii) the affinity for 6-deoxy-D
      glucose (6-DOG) is two orders of magnitude lower than that for D-glucose, whereas
      the bloodstream-form transporter recognizes D-glucose and its 6-DOG analogue with
      similar affinity; (iii) the bloodstream-form transporter, but not THT2,
      recognizes 3-fluoro-3-deoxy-D-glucose. D-Fructose-transport capacity and
      insensitivity to D-galactose was also found in THT2-expressing CHO cells and
      procyclic trypanosomes. We conclude from these cumulative results that the THT2
      gene encodes the transporter responsible for hexose transport in procyclic
      trypanosomes. The transport of 2-DOG in procyclic organisms was inhibited by both
      the protonophore, carbonyl cyanide 4-trifluoromethoxy phenylhydrazone (FCCP), and
      KCN, suggesting a requirement for a protonmotive force. However, sensitivity to
      these reagents depended on the external substrate concentration, with uptake
      being unaffected at substrate concentrations higher than 2 mM. THT2 expressed in
      CHO cells behaved as a facilitated transporter, and was unaffected by FCCP or KCN
      over the whole substrate concentration range tested.

PMID- 8554507
TI  - Differential regulation of cyclin A, cyclin B and p21 concentrations in a growth
      restricted human fibroblast cell line.
AB  - When the culture temperature was shifted from 35 degrees C to 39 degrees C, human
      fibroblasts immortalized by the temperature-sensitive simian virus 40 T antigen
      became larger and acquired the morphological characteristics of senescent
      fibroblasts. After culture at 39 degrees C for 48 h, most cells had ceased to
      proliferate. A rapid depletion of cells with S-phase DNA content was observed
      after the temperature shift. To elucidate the mechanism governing this rapid
      arrest of proliferation, we studied the expression of genes involved in the
      regulation of cell cycle progression. Cyclin A, cyclin B and p34cdc2
      concentrations were not changed during growth restriction, whereas p21 was
      rapidly induced in these growth-restricted cells. Transient expression of
      exogenous p21 in cells cultured at 35 degrees C led to growth restriction and
      morphological changes characteristic of senescence. Furthermore, we studied the
      reversibility of growth restriction induced by the temperature increase. The
      results showed that senescent morphology and growth arrest were not reversible.
      In these cells the p21 concentration remained high and p34cdc2 remained
      undetectable. This indicates that p21 accumulation might be responsible for the
      maintenance of senescence. Our findings provide information on the use of growth
      restriction of immortalized fibroblasts induced by a temperature shift as a model
      system to study senescence.

PMID- 8554508
TI  - Early events in erythroid differentiation: accumulation of the acidic peroxidoxin
      (PRP/TSA/NKEF-B).
AB  - The acidic peroxidoxin [also named thiol-specific antioxidant protein (TSA) or
      protector protein (PRP)], which plays a role in the response against oxidative
      stress, is one of the major proteins of red blood cells. In this work, we show
      that this protein is induced at early stages of erythroid differentiation prior
      to haemoglobin accumulation, which suggests that it may play a role at the
      erythroblast stage, where haemoglobinized, nucleated and genetically active cells
      are submitted to a maximally dangerous oxidative stress. The early accumulation
      of this protein has been demonstrated both on transformed cell systems and on
      normal differentiating human erythroid cells. This suggests that this protein may
      play an important role in the differentiation of the erythroid cells.

PMID- 8554509
TI  - Modulatory role of platelet-derived growth factor on cytokine-induced nerve
      growth factor synthesis in rat glomerular mesangial cells.
AB  - Recent evidence indicates that cytokines are potent inducers of nerve growth
      factor (NGF) expression in peripheral tissues and in brain. Cultured rat
      glomerular mesangial cells respond to interleukin-1 beta (IL-1 beta) and tumour
      necrosis factor-alpha (TNF-alpha) by increased NGF synthesis. We found that co
      stimulation of rat glomerular mesangial cells with platelet-derived growth factor
      (PGDF-BB) and IL-1 beta/TNF-alpha significantly augments the IL-1 beta/TNF-alpha
      induced NGF mRNA levels and NGF synthesis. In contrast, preincubation with PDGF
      BB drastically reduces NGF gene expression and NGF protein synthesis in response
      to IL-1 beta/TNF-alpha stimulation. Thus our results indicate that PDGF-BB is a
      potent modulator of cytokine-induced NGF expression; its precise action is
      critically depending on the time at which the PDGF receptor is activated.

PMID- 8554510
TI  - Identification of polymorphism at the glutathione S-transferase, GSTM3 locus:
      evidence for linkage with GSTM1*A.
AB  - Allelism in the glutathione S-transferase, GSTM3 gene has been identified using
      PCR with specific primers to exon 6/exon 7. Sequencing showed the mutant GSTM3*B
      allele to have a three-base deletion in intron 6 with a frequency of 0.158. The
      mutation generates a recognition sequence, 5'-AAGATA-3', for the negative
      transcription factor YY1. GSTM3*B was significantly associated with GSTM1*A.

PMID- 8554511
TI  - Urea synthesis in enterocytes of developing pigs.
AB  - Urea synthesis from ammonia, glutamine and arginine was determined in enterocytes
      from newborn (0-day-old), 2-21-day-old suckling, and 29-58-day-old post-weaning
      pigs. Pigs were weaned at 21 days of age. Cells were incubated for 30 min at 37
      degrees C in Krebs-Henseleit bicarbonate buffer (pH 7.4) containing (i) 0.5-2 mM
      NH4Cl plus 0.05-2 mM ornithine and 2 mM aspartate, (ii) 1-5 mM glutamine, or
      (iii) 0.5-2 mM arginine. In enterocytes from newborn and suckling pigs, there was
      no measurable synthesis of urea from ammonia, glutamine or arginine, and analysis
      of amino acids by a sensitive fluorimetric HPLC method revealed the formation of
      negligible amounts of ornithine from arginine. In contrast, in cells from post
      weaning pigs, relatively large amounts of urea and ornithine were produced from
      ammonia, glutamine and arginine in a dose-dependent manner. To elucidate the
      mechanism of the developmental change of urea synthesis in pig enterocytes, the
      activities of urea-cycle enzymes were determined. The activities of enterocyte
      carbamoyl phosphate synthase I and ornithine carbamoyltransferase were lower in
      post-weaning pigs than in suckling ones, whereas there was no difference in
      arginino-succinate lyase. The activities of argininosuccinate synthase and
      arginase were increased by 4-fold and 50-100-fold, respectively, in enterocytes
      from post-weaning pigs compared with suckling pigs. The induction of arginase
      appears to be sufficient to account for the formation of urea from ammonia,
      glutamine and arginine in post-weaning pig enterocytes. These results demonstrate
      for the first time the presence of synthesis of urea from extracellular or
      intramitochondrially generated ammonia in enterocytes of post-weaning pigs. This
      hitherto unrecognized urea synthesis in these cells may be a first line of
      defence against the potential toxicity of ammonia produced by the extensive
      intestinal degradation of glutamine (a major fuel for enterocytes) and derived
      from diet and luminal micro-organisms.

PMID- 8554512
TI  - Albumin binding of insulins acylated with fatty acids: characterization of the
      ligand-protein interaction and correlation between binding affinity and timing of
      the insulin effect in vivo.
AB  - Albumin is a multifunctional transport protein that binds a wide variety of
      endogenous substances and drugs. Insulins with affinity for albumin were
      engineered by acylation of the epsilon-amino group of LysB29 with saturated fatty
      acids containing 10-16 carbon atoms. The association constants for binding of the
      fatty acid acylated insulins to human albumin are in the order of 10(4)-10(5) M
      1. The binding apparently involves both non-polar and ionic interactions with the
      protein. The acylated insulins bind at the long-chain fatty acid binding sites,
      but the binding affinity is lower than that of the free fatty acids and depends
      to a relatively small degree on the number of carbon atoms in the fatty acid
      chain. Differences in affinity of the acylated insulins for albumin are reflected
      in the relative timing of the blood-glucose-lowering effect after subcutaneous
      injection into rabbits. The acylated insulins provide a breakthrough in the
      search for soluble, prolonged-action insulin preparations for basal delivery of
      the hormone to the diabetic patient. We conclude that the biochemical concept of
      albumin binding can be applied to protract the effect of insulin, and suggest
      that derivatization with albumin-binding ligands could be generally applicable to
      prolong the action profile of peptide drugs.

PMID- 8554513
TI  - Ethanol has different effects on Ca(2+)-transport ATPases of muscle, brain and
      blood platelets.
AB  - The effects of ethanol on different sarco/endoplasmic reticulum Ca(2+)-transport
      ATPases (SERCAs) were studied. In sarcoplasmic reticulum vesicles, ethanol
      concentrations varying from 5 to 20% promoted a progressive inhibition of Ca2+
      uptake, enhancement of Ca2+ efflux, activation of the ATPase activity, increase
      of the enzyme phosphorylation by ATP and inhibition of enzyme phosphorylation by
      P1. The effects of ethanol on Ca2+ uptake and Ca2+ efflux were antagonized by
      Mg2+, P(i) and spermine. The increased efflux promoted by ethanol was antagonized
      by Ca2+ and thapsigargin. In brain and platelet vesicles a biphasic effect of
      ethanol was observed, so that activation occurred at low concentrations (5-10%)
      and inhibition at higher concentrations. The activation was not observed with the
      use of n-propanol and n-butanol. Different from the situation in sarcoplasmic
      reticulum, the decrease of the Ca2+ uptake in brain and platelet vesicles was
      associated with an inhibition of the ATPase activity. Mg2+ and P(i) antagonized
      the enhancement of Ca2+ efflux and the inhibition of Ca2+ uptake promoted by
      ethanol. However, thapsigargin and Ca2+ did not arrest the Ca2+ efflux promoted
      by ethanol in brain and platelet preparations. These results suggest that, in
      sarcoplasmic reticulum vesicles, ethanol uncouples the pump, promoting its
      activity as a Ca2+ channel. The SERCA isoform found in skeletal muscle has
      different properties from the isoforms found in brain and blood platelets.

PMID- 8554515
TI  - Stable intracellular acidification upon polyamine depletion induced by alpha
      difluoromethylornithine or N1,N12-bis(ethyl)spermine in L1210 leukaemia cells.
AB  - Polyamines play major roles in ionic and osmotic regulation, but their exact
      involvement in specific ion transport processes is poorly defined. Treatment of
      L1210 mouse leukaemia cells with either 5 mM alpha-difluoromethylornithine
      (DFMO), a suicide substrate of ornithine decarboxylase, or 25 microM N1,N12
      bis(ethyl)spermine (BE-3-4-3), a dysfunctional polyamine analogue, caused a
      stable decreased in intracellular pH (pHi) by 0.1-0.4 unit from steady-state
      control values between 7.4 and 7.6, as measured either by partition of a weak
      acid or with a fluorescent pH-sensitive probe. This effect was not related to
      cell growth status or differences in metabolic acid generation, and was observed
      in either the presence or absence of HCO3-. Exogenous spermidine (10-25 microM)
      or putrescine (25-50 microM) fully reversed DFMO- or BE-3-4-3-induced
      acidification within 2 and 8 h respectively. Recovery of pHi in L1210 cells after
      a nigericin- or NH4(+)-mediated acid load in HCO3(-)-free buffers was mediated by
      Na+/H+ antiporter activity, in addition to a minor Na(+)-independent and
      amiloride-insensitive pathway. Decreased steady-state pHi was maintained in
      polyamine-depleted L1210 cells after recovery from acid stress. Moreover, the pHi
      dependence of the rate of Na(+)-dependent H+ extrusion after an acid stress was
      altered by DFMO and BE-3-4-3, resulting in a set-point which was lower by 0.25
      0.30 pH unit in polyamine-depleted cells. On the other hand, neither the rate nor
      the magnitude of Na+/H(+)-exchanger-mediated alkalinization induced by hypertonic
      shock was decreased by polyamine depletion. Thus polyamine depletion induces a
      persistent defect in pHi homeostasis which is due, at least in part, to a stable
      decrease in the pHi set-point of the Na+/H+ exchanger.

PMID- 8554514
TI  - The first putative transmembrane helix of the 16 kDa proteolipid lines a pore in
      the Vo sector of the vacuolar H(+)-ATPase.
AB  - The 16 kDa proteolipid is the major component of the vacuolar H(+)-ATPase
      membrane sector, responsible for proton translocation. Expression of a related
      proteolipid from the arythropod Nephrops norvegicus in a Saccharomyces strain in
      which the VMA3 gene for the endogenous proteolipid has been disrupted results in
      restored vacuolar H(+)-ATPase function. We have used this complementation system,
      coupled to cysteine substitution mutagenesis and protein chemistry, to
      investigate structural features of the proteolipid. Consecutive cysteines were
      introduced individually into putative transmembrane segment 1 of the proteolipid,
      and at selected sites in extramembranous regions and in segment 3 and 4. Analysis
      of restored vacuolar H(+)-ATPase function showed that segment 1 residues
      sensitive to mutation to cysteine were clustered on a single face, but only if
      the segment was helical. Only residues insensitive to mutation could be
      covalently modified by the cysteine-specific reagent fluorescein 5-maleimide. A
      cysteine introduced into segment 3 was the only residue accessible to a
      relatively hydrophobic reagent, suggesting accessibility to the lipid phase.
      Analysis of disulphide bond formation between introduced cysteines indicates that
      the first transmembrane alpha-helices of each monomer are adjacent to each other
      at the centre of the proteolipid multimeric complex. The data are consistent with
      a model in which the fluorescein maleimide-accessible face of helix I lines a
      pore at the centre of a hexameric complex formed by the proteolipid, with the
      mutationally sensitive face oriented into the protein core. The implications for
      ion-transport function in this family of proteins are discussed in the context of
      this structural model.

PMID- 8554516
TI  - Sugar-dependent expression of the fructose transporter GLUT5 in Caco-2 cells.
AB  - The effect of glucose and fructose and fetal bovine serum on the expression of
      the fructose transporter GLUT5 was studied in clone PD7 of the human colon cancer
      cell line Caco-2, which has been characterized previously [Chantret, Rodoloswe,
      Barbat et al. (1994) J. Cell Sci. 107, 213-225; Mahraoui, Rodolosse, Barbat et
      al. (1994) Biochem. J. 298, 629-633]. Culture of the cells in dialysed serum and
      hexose-free media, down-regulated the expression of GLUT5, which was below
      detection within 3-4 days. This effect was reversed by fructose and glucose
      feeding of the cells. Fructose feeding yielded a 3-fold higher abundance of GLUT5
      protein and mRNA as compared with that expressed in glucose-fed cells. Cells fed
      normal serum exhibited an inverse hierarchy of expression, with glucose being a
      better inducer than fructose for the expression of GLUT5. The GLUT5 mRNA and
      protein abundances obtained in fructose-fed cells did not depend on the type of
      serum. A linear relationship between cyclic AMP (cAMP) levels and GLUT5 mRNA
      abundance was found in cells fed dialysed serum, whereas in cells fed normal
      serum, mRNA abundances were not correlated to cAMP levels. These results indicate
      that glucose and fructose, together with serum-related factors and cAMP, have
      combined effects on the expression of GLUT5 in Caco-2 cells.

PMID- 8554517
TI  - Cross-talk between glucagon- and adenosine-mediated signalling systems in rat
      hepatocytes: effects on cyclic AMP-phosphodiesterase activity.
AB  - The effect of adenosine analogues on glucagon-stimulated cyclic AMP accumulation
      in rat hepatocytes was explored. N6-Cyclopentyladenosine (CPA), 5'-N
      ethylcarboxamidoadenosine and N6-(R-phenylisopropyl)adenosine inhibited in a dose
      dependent manner the cyclic AMP accumulation induced by glucagon. This effect
      seems to be mediated through A1 adenosine receptors. Pertussis toxin completely
      abolished the effect of CPA on glucagon-stimulated cyclic AMP accumulation in
      whole cells which suggested that a pertussis-toxin-sensitive G-protein was
      involved. On the other hand, this action of adenosine analogues on glucagon
      induced cyclic AMP accumulation was reverted by the selective low-Km cyclic AMP
      phosphodiesterase inhibitor Ro 20-1724. Analysis of cyclic AMP-phosphodiesterase
      activity in purified hepatocyte plasma membranes showed that glucagon in the
      presence of GTP inhibited basal PDE activity by 45% and that CPA reverted this
      inhibition in dose-dependent manner. In membranes derived from pertussis-toxin
      treated rats, we observed no inhibition of cyclic AMP-phosphodiesterase activity
      by glucagon in the absence or presence of CPA. Our results indicate that in
      hepatocyte plasma membranes, stimulation of adenylate cyclase activity and
      inhibition of a low-Km cyclic AMP phosphodiesterase activity are co-ordinately
      regulated by glucagon, and that A1 adenosine receptors can inhibit glucagon
      stimulated cyclic AMP accumulation by blocking glucagon's effect on
      phosphodiesterase activity.

PMID- 8554518
TI  - Insulin and vasopressin elicit inhibition of cholera-toxin-stimulated adenylate
      cyclase activity in both hepatocytes and the P9 immortalized hepatocyte cell line
      through an action involving protein kinase C.
AB  - Incubation of hepatocytes or the SV40-DNA-immortalized hepatocyte P9 cell line
      with cholera toxin led to a time-dependent activation of adenylate cyclase
      activity, which occurred after a defined lag period. When added together with
      cholera toxin, each of the hormones insulin and vasopressin was capable of
      attenuating the maximum stimulatory effect achieved by cholera toxin over a
      period of 60 min through a process which could be blocked by the compounds
      staurosporine and chelerythrine. Attenuating effects on cholera-toxin-stimulated
      adenylate cyclase activity could also be elicited by using either the protein
      kinase C (PKC)-stimulating phorbol ester PMA (phorbol 12-myristate 13-acetate) or
      the protein phosphatase inhibitor okadaic acid. Alkaline phosphatase treatment of
      membranes reversed the inhibitory effect of PMA. Cholera toxin also stimulated
      the adenylate cyclase activity of intact CHO (Chinese-hamster ovary) and NIH-3T3
      cells, but this activity was insensitive to the addition of PMA. Overexpression
      of various PKC isoforms in CHO cell lines did not confer sensitivity to
      inhibition by PMA upon cholera-toxin-stimulated adenylate cyclase activity.
      Rather, overexpression of the gamma isoform of PKC allowed PMA to stimulate
      adenylate cyclase activity in CHO cells. It is suggested that the PKC-mediated
      phosphorylation of a membrane protein attenuates cholera-toxin-stimulated
      adenylate cyclase activity in hepatocytes and P9 cells. The cellular selectivity
      of such an action may be due to the target for this inhibitory action of PKC
      being a particular isoform of adenylate cyclase which provides the major activity
      in hepatocytes and P9 cells, but not in either CHO or NIH-3T3 cells.

PMID- 8554519
TI  - The human platelet ADP receptor activates Gi2 proteins.
AB  - We have previously shown that platelet ADP receptors are coupled to G-proteins by
      measuring the binding of [35S]guanosine-5'-[gamma-thio]triphosphate ([35S]GTP
      gamma S) to human platelet membranes stimulated with ADP. In order to identify
      the activated G-proteins, we used an approach which combines photolabelling of
      receptor-activated G-proteins with 4-azidoanilido-[alpha-32P]GTP and
      immunoprecipitation of the G-protein alpha-subunits with subtype-specific
      antibodies. Stimulation of human platelet membranes with ADP resulted in an
      increase in 4-azidoanilido-[alpha-32P]GTP incorporation into the
      immunoprecipitates of G alpha i but not of G alpha q proteins, whereas
      stimulation with the thromboxane analogue U46619 resulted in an increase in 4
      azidoanilido-[alpha-32P]GTP incorporation into the immunoprecipitates of G alpha
      q but not of G alpha i proteins, and thrombin activated both G-proteins. This
      effect of ADP was concentration dependent and inhibited by the class P2
      purinoceptor (P2T) antagonist ATP. Using specific antisera against subtypes of Gi
      proteins, we found that ADP stimulated labelling of the G alpha 12
      immunoprecipitate, but not of the G alpha 13 precipitate. G alpha i1 was not
      detectable by immunoblotting of platelet membrane proteins. These data suggest
      that ADP inhibits cAMP formation by activation of G alpha 12 proteins and add
      evidence in support of the hypothesis that human platelet ADP receptors do not
      activate PLC through Gq activation.

PMID- 8554520
TI  - Early alterations in the brown adipose tissue adenylate cyclase system of pre
      obese Zucker rat fa/fa pups: decreased G-proteins and beta 3-adrenoceptor
      activities.
AB  - This study was undertaken to determine whether receptor and non-receptor
      components of the adenylate cyclase (AC) cascade were altered in brown adipose
      tissue (BAT) of 14-day-old pre-obese (fa/fa) rats, before endocrine status is
      strongly modified by fa gene expression. Activity of the AC catalytic subunit did
      not differ between the two genotypes. In fa/fa rats compared with control Fa/fa
      rats, there was a 50% decrease in the activity of alpha Gs (stimulated by NaF or
      guanosine 5'-[gamma-thio]triphosphate) but no change in protein content (Western
      blotting). alpha Gi function, assessed by the inhibitory action of low
      concentrations of guanosine 5'-[beta gamma-imido]triphosphate upon 10(-4) M
      forskolin-stimulated AC activity, was equally low in both genotypes. Analysis of
      dose-response curves for different beta-agonists revealed that (i) both the basal
      and the maximally stimulated activity of AC were 2-fold lower in fa/fa rats than
      in Fa/fa rats; (ii) BRL37344 and CGP12177 (beta 3 agonists) were less potent in
      fa/fa than in Fa/fa rats (Kact. multiplied by 2); (iii) noradrenaline and
      isoprenaline (Iso), at the low-affinity site (beta 3-AR), were less potent in
      fa/fa than in Fa/fa pups (Kact. increased by 30 and 20% respectively). At the
      high-affinity site (mainly beta 1) these two agonists were more potent in fa/fa
      than in Fa/fa rats (Kact. decreased by 40 and 80% respectively). In good
      agreement with the latter result, the beta 1-adrenergic receptor (beta 1-AR)
      selective antagonist CGP20712A had more effect on the Iso-stimulated AC activity
      in pre-obese than in lean pups (2-fold decreased in IC50). Binding experiments
      with [3H]CGP12177 show that in BAT of suckling rats, beta 3-ARs represent 80% of
      the total beta-ARs. Bmax values for the two sites were not affected by the
      genotype, although the beta 3-AR mRNA concentration in BAT (quantitative reverse
      transcriptase PCR) was 3-fold lower in fa/fa rats than in Fa/fa pups. In
      conclusion, these results provide evidence for alterations in beta 1- and beta 3
      AR signalling in BAT of 14-day-old suckling pre-obese Zucker rats with a
      decreased activity of alpha Gs. The impaired AC responsiveness to catecholamines
      might be a primary contributor to the development of this genetic obesity.

PMID- 8554521
TI  - Quantal responses to inositol 1,4,5-trisphosphate are not a consequence of Ca2+
      regulation of inositol 1,4,5-trisphosphate receptors.
AB  - Submaximal concentrations of inositol 1,4,5-trisphosphate (InsP3) rapidly release
      only a fraction of the InsP3-sensitive intracellular Ca2+ stores, despite the
      ability of further increases in InsP3 concentration to evoke further Ca2+
      release. The mechanisms underlying such quantal Ca2+ mobilization are not
      understood, but have been proposed to involve regulatory effects of cytosolic
      Ca2+ on InsP3 receptors. By examining complete concentration-effect relationships
      for InsP3-stimulated 45Ca2+ efflux from the intracellular stores of permeabilized
      hepatocytes, we demonstrate that, at 37 degrees C, responses to InsP3 are quantal
      in Ca(2+)-free media heavily buffered with either EGTA or BAPTA [1,2-bis-(2
      aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid]. Lower concentrations of InsP3
      were used to examine the kinetics of Ca2+ mobilization at 2 degrees C, because at
      the lower temperature the stores were more sensitive to InsP3: the concentration
      of InsP3 causing half-maximal Ca2+ release (EC50) after a 30 s incubation
      decreased from 281 +/- 37 nM at 37 degrees C to 68 +/- 3 nM at 2 degrees C. At 2
      degrees C, the EC50 for InsP3-stimulated Ca2+ mobilization decreased as the
      duration of exposure to InsP3 was increased: the EC50 was 68 +/- 3 nM after 30 s,
      and 29 +/- 2 nM after 420 s. InsP3-stimulated Ca2+ mobilization is therefore non
      quantal at 2 degrees C: InsP3 concentration determines the rate, but not the
      extent, of Ca2+ release. By initiating quantal responses to InsP3 at 37 degrees C
      and then simultaneously diluting and chilling cells to 2 degrees C, we
      demonstrated that the changes that underlie quantal responses do not rapidly
      reverse at 2 degrees C. At both 37 degrees C and 2 degrees C, modest increases in
      cytosolic Ca2+ increased the sensitivity of the stores to InsP3, whereas further
      increases were inhibitory; both Ca2+ effects persisted after prior removal of
      ATP. We conclude that the effects of Ca2+ on InsP3 receptors are unlikely either
      to be enzyme-mediated or to underlie the quantal pattern of Ca2+ release evoked
      by InsP3.

PMID- 8554522
TI  - Partial characterization of regulation of biliary lecithin hydrophobicity:
      association with organic anion-induced solute cholestasis in rats.
AB  - We examined the effects of the depletion of bile salts and of the intravenous
      infusion of sodium taurocholate (STC) with or without bromosulphophthalein (BSP)
      in rats on the biliary secretion of lipids to clarify the regulatory
      mechanism(s). Each rat was equipped with a bile-duct cannula to collect bile.
      After the endogenous bile salt pool was depleted, STC was infused at a constant
      rate (160 nmol/min per 100 g body wt.) with or without BSP (50, 100, or 150
      nmol/min per 100 g body wt.). BSP reduced the biliary secretion of cholesterol
      and phospholipids dose-dependently without affecting the secretion of bile salts
      (uncoupling phenomenon). Compared with the physiological and STC-infused
      condition, the biliary cholesterol/phospholipid ratio and saturated/unsaturated
      fatty acid ratio increased under the bile salts depletion and uncoupling
      phenomenon. Data indicate that the hydrophobicity of biliary lecithin increases
      with a decrease in the bile salt micelle capacity to induce biliary lipid
      secretion, resulting in a higher packing density of biliary vesicle. The
      cholesterol-holding capacity of the biliary vesicle is therefore enhanced during
      the depletion of bile salts and the uncoupling phenomenon.

PMID- 8554523
TI  - Potentiated bradykinin-induced increase of 1,2-diacylglycerol generation and
      phospholipase D activity in human senescent fibroblasts.
AB  - 1. The comparative study of the effect of bradykinin (BK) in young and old IMR-90
      human fibroblasts shows that old cells are characterized by a reduced increase in
      1,2-diacylglycerol (1,2-DAG) generation upon stimulation after short-term
      treatment and a significant higher increase after long-term agonist treatment. BK
      induced activation of phospholipase D (PLD), the major enzyme involved in
      sustained 1,2-DAG generation, was 2.5-fold higher in old cells, strongly
      suggesting that it is involved in the potentiated increase of 1,2-DAG formation.
      The increased activation of PLD by BK in old cells was specific, since in
      parallel experiments the effect of thrombin was not significantly different in
      young and old cells. PLD activity in old cells was only reduced by down
      regulation of protein kinase C (PKC) activity, in contrast to what was observed
      in young cells where it was completely abolished. This indicates that the enzyme
      activity in old cells was partially PKC-independent. BK was also able to increase
      the release of [14C]ethanolamine, a water-soluble product of hydrolysis of
      phosphatidylethanolamine (PtdEtn), through PLD activation in young and old cells.
      The BK effect was significantly higher in old cells and, very likely, PKC
      independent, since phorbol 12-myristate 13-acetate failed to induce PtdEtn
      hydrolysis. 2. The present results indicate that the PLD/1,2-DAG pathway is
      specifically potentiated by BK in old fibroblasts, demonstrating that the
      formation of positive effectors of PKC activation is not necessarily decreased in
      cellular senescence. It remains to be established whether the increased
      generation of DAG upon BK stimulation plays any role in the altered PKC
      signalling pathway which characterizes old fibroblasts.

PMID- 8554524
TI  - Evidence for receptor and G-protein regulation of a phosphatidylethanolamine
      hydrolysing phospholipase A1 in guinea-pig heart microsomes: stimulation of
      phospholipase A1 activity by DL-isoprenaline and guanine nucleotides.
AB  - While evidence has been presented for the receptor-mediated activation of
      phospholipases A2, C and D, the activation of phospholipase A1 subsequent to
      receptor activation has not been established. Phospholipase A1-catalysed
      hydrolysis of 1-palmitoyl-2-linoleoyl-glycerophosphoethanolamine (GPE) by guinea
      pig heart microsomes was stimulated 40-60% by isoprenaline. This isoprenaline
      mediated increase in activity was blocked by propranolol and butoxamine, a
      specific beta 2-adrenergic antagonist, but not by atenolol, a specific beta 1
      adrenergic antagonist. Neither clonidine nor phenylephrine, alpha 1- and alpha 2
      adrenergic agonists respectively, had a stimulatory effect on the hydrolysis of
      the PE substrate. Guanosine 5'(-)[gamma-thio]triphosphate (GTP[S]) and guanosine
      5'(-)[beta,gamma-imido]triphosphate, but not guanosine 5'(-)[beta
      thio]diphosphate (GDP[S]) or adenosine 5'(-)[gamma-thio]triphosphate, stimulated
      the hydrolysis of 1-palmitoyl-2-linoleoyl-GPE by phospholipase A1. GDP[S]
      inhibited the isoprenaline-mediated stimulation of phospholipase A1 activity.
      Phospholipase A1 hydrolysis of 1-palmitoyl-2-linoleoyl-GPE was not dependent on
      cations; however, the stimulatory effects of isoprenaline and GTP[S] on the
      hydrolytic activity were abolished by cation chelators. The above data suggest
      that phospholipase A1 activity in guinea-pig heart microsomes is activated by the
      binding of isoprenaline to beta 2-adrenergic receptors. Furthermore the
      stimulation of phospholipase A1 activity by the agonist may be mediated via
      activation of G-proteins.

PMID- 8554525
TI  - Temperature-dependent changes in plasma-membrane lipid order and the phagocytotic
      activity of the amoeba Acanthamoeba castellanii are closely correlated.
AB  - The relationship between temperature-dependent changes in phagocytotic activity
      of Acanthamoeba castellanii and the fatty acid composition and physical
      properties of plasma membrane-enriched fractions were determined in cultures
      acclimated to 30 degrees C and 15 degrees C. Chilling (from 30 degrees C to 15
      degrees C) had a very pronounced short-term inhibitory effect on phagocytosis
      only in stationary-phase cultures, which displayed a low degree of fatty acid
      unsaturation. A subsequent increase in phagocytosis by these cells was correlated
      with a low-temperature-induced increase in fatty acid unsaturation (shown
      previously [Jones, Lloyd and Harwood (1993) Biochem. J. 296, 183-188] to be due
      to n-6 desaturase induction). Plasma membrane-enriched fractions from 15 degrees
      C-acclimated cells also showed a marked increase in the relative proportion of
      polyunsaturated fatty acids. Steady-state fluorescence depolarization studies,
      using the membrane probe diphenylhexatriene, revealed increases in plasma
      membrane order with decreasing assay temperature. Over the upper assay
      temperature range (25-40 degrees C), fluorescence anisotropy values were higher
      in membranes from 30 degrees C-acclimated cells; a 3.3 degrees C relative
      displacement of plots indicated that temperature-induced changes in membrane
      lipid composition compensated for approx. 22% of the ordering effect of low
      temperature. Changes in the temperature-dependence of fluorescence anisotropy,
      possibly corresponding to lateral phase separations or alterations in other bulk
      physical properties of membranes, occurred between 20 and 25 degrees C in
      membranes from 30 degrees C-acclimated cells and between 15 and 20 degrees C in
      membranes from 15 degrees C-acclimated cells. Fluorescence anisotropy plots were
      superimposed at assay temperatures between 5 and 15 degrees C. Short-term
      phagocytotic rates in whole cells decreased with assay temperature. Arrhenius
      discontinuities in rates of phagocytosis occurred at approx. 25.0 degrees C and
      17.5 degrees C in 30 degrees C- and 15 degrees C-acclimated cells respectively,
      and in each case were thus within the temperature ranges of slope-change in the
      corresponding fluorescence anisotropy plots. The results show a direct
      correlation between plasma membrane fatty acid unsaturation, membrane physical
      properties and phagocytotic activity in A. castellanii. Therefore, a specific
      integrated physiological process has been correlated with fatty acid desaturase
      induction for the first time.

PMID- 8554526
TI  - Polymorphism of the yeast pyruvate carboxylase 2 gene and protein: effects on
      protein biotinylation.
AB  - In Saccharomyces cerevisiae there are two isoenzymes of pyruvate carboxylase
      (Pyc) encoded by separate genes designated PYC1 and PYC2. We report the isolation
      and sequencing of a PYC2 gene, and the localization of both genes on the physical
      map of S. cerevisiae. Comparison with the previously reported sequence [Stucka,
      Dequin, Salmon and Gancedo (1991) Mol. Gen. Genet. 229, 307-315] revealed
      significant differences within the open reading frame. The most notable
      difference was near the 3' end, where we found a single base deletion reducing
      the open reading frame by 15 bases. We have confirmed the C-terminus of Pyc2
      encoded by the gene isolated here by expressing and purifying an 86-amino-acid
      biotin-domain peptide. In addition, we investigated the effects of the two
      changes in the Pyc2 biotin domain (K1155R substitution and Q1178P/five-amino-acid
      extension) on the extent of biotinylation in vivo by Escherichia coli biotin
      ligase, and compared the biotinylation of peptides containing these changes with
      that of two different-length Pyc1 biotin-domain peptides. The K1155R substitution
      had very little effect on biotinylation, but the five-amino-acid C-terminal
      extension to Pyc2 and the N-terminal extension to Pycl both improved
      biotinylation in vivo.

PMID- 8554527
TI  - DNA elements with AT-rich core sequences direct pituitary cell-specific
      expression of the pro-opiomelanocortin gene in transgenic mice.
AB  - Corticotrophs are the first fully differentiated cells to appear in the anterior
      pituitary during organogenesis and are distinguished by pro-opiomelanocortin
      (POMC) gene expression. Earlier studies in our laboratory defined three DNA
      regions (sites 1, 2 and 3) within promoter sequences at the 5'-end of the rat
      POMC gene (-323/-34) that cooperatively targeted cell-specific gene expression to
      corticotrophs and melanotrophs in transgenic mice. In this study we analysed the
      DNA-nuclear protein interactions underlying this functional activity. We
      demonstrated that the transcriptional activator SP1 interacts with GC-rich
      regions in sites 1 (-146/-136) and 2 (-201/-192) and an unidentified protein,
      which we call PP1 (putative pituitary POMC1), interacts with AT-rich regions in
      sites 2 (-202/-193) and 3 (-262/-253). The PP1-binding activity appears to be
      specific to cells that express the POMC gene because it was detected in nuclear
      extracts prepared from AtT20 corticotroph cells and mouse melanotroph tumours but
      not from GH4 pituitary tumour cells, HeLa cells or liver. Site-directed
      mutagenesis of core binding sequences demonstrated that PP1 is required for the
      correct cell-specific expression of the POMC gene in the pituitary gland of
      transgenic mice and SP1 appears to support such an expression. The best core
      binding sequence for PP1 is TAAT, a possible transcription factor homeodomain
      contact site. However, PP1 is distinct from Brn 3.0, a POU protein that also
      binds to site 3. We conclude that PP1 is a transcriptional activator for
      pituitary-specific POMC gene expression.

PMID- 8554528
TI  - Constitutive nuclear NF kappa B/rel DNA-binding activity of rat thymocytes is
      increased by stimuli that promote apoptosis, but not inhibited by pyrrolidine
      dithiocarbamate.
AB  - Rat thymocytes spontaneously undergo apoptotic death in cell culture, and are
      also sensitive to the induction of apoptosis by various stimuli. We show that
      unstimulated thymocytes constitutively express a p50-containing nuclear factor
      kappa B (NF kappa B)/rel DNA-binding activity in their nuclei. When the cells
      were fractionated by density-gradient centrifugation this activity was found to
      be most pronounced in immature CD4+8+ thymocytes, the cell population that
      undergoes selection by apoptosis in vivo and that is most sensitive to external
      inducers of apoptosis in vitro. The intensity of the NF kappa B/rel protein-DNA
      complex was significantly enhanced 30 min after exposing thymocytes to
      methylprednisolone or etoposide, two agents well known to induce apoptosis in
      these cells. Expression of this DNA-binding activity therefore correlates with
      the subsequent occurrence of apoptosis. By analogy to other systems, it has been
      suggested that antioxidants such as pyrrolidine dithiocarbamate (PDTC) inhibit
      thymocyte apoptosis by preventing the activation of an NF kappa B/rel
      transcription factor. However, we have found that etoposide induces a very
      similar enhancement of the NF kappa B/rel DNA-binding activity in the presence or
      absence of PDTC, despite a pronounced inhibition of apoptotic DNA fragmentation
      in the former situation. Dithiocarbamates therefore do not exert their anti
      apoptotic activity in thymocytes by inhibiting the activation of this
      transcription factor.

PMID- 8554529
TI  - Lactoferrin-lipopolysaccharide interaction: involvement of the 28-34 loop region
      of human lactoferrin in the high-affinity binding to Escherichia coli 055B5
      lipopolysaccharide.
AB  - The ability of lactoferrin (Lf), an iron-binding glycoprotein that is also called
      lactotransferrin, to bind lipopolysaccharide (LPS) may be relevant to some of its
      biological properties. A knowledge of the LPS-binding site on Lf may help to
      explain the mechanism of its involvement in host defence. Our report reveals the
      presence of two Escherichia coli 055B5 LPS-binding sites on human Lf (hLf): a
      high-affinity binding site (Kd 3.6 +/- 1 nM) and a low-affinity binding site (Kd
      390 +/- 20 nM). Bovine Lf (bLf), which shares about 70% amino acid sequence
      identity with hLf, exhibits the same behaviour towards LPS. Like hLf, bLf also
      contains a low- and a high-affinity LPS-binding site. The Kd value (4.5 +/- 2 nM)
      corresponding to the high-affinity binding site is similar to that obtained for
      hLf. Different LPS-binding sites for human serum transferrin have been suggested,
      as this protein, which is known to bind bacterial endotoxin, produced only 12%
      inhibition of hLf-LPS interaction. Binding and competitive binding experiments
      performed with the N-tryptic fragment (residues 4-283), the C-tryptic fragment
      (residues 284-692) and the N2-glycopeptide (residues 91-255) isolated from hLf
      have demonstrated that the high-affinity binding site is located in the N
      terminal domain I of hLf, and the low-affinity binding site is present in the C
      terminal lobe. The inhibition of hLf-LPS interaction by a synthetic
      octadecapeptide corresponding to residues 20-37 of hLf and lactoferricin B
      (residues 17-41), a proteolytic fragment from bLf, revealed the importance of the
      28-34 loop region of hLf and the homologous region of bLf for LPS binding. Direct
      evidence that this amino acid sequence is involved in the high-affinity binding
      to LPS was demonstrated by assays carried out with EGS-loop hLf, a recombinant
      hLf mutated at residues 28-34.

PMID- 8554530
TI  - Biosynthesis of recombinant human pro-alpha 1(III) chains in a baculovirus
      expression system: production of disulphide-bonded and non-disulphide-bonded
      species containing full-length triple helices.
AB  - We have investigated the expression of human procollagen III by insect cells
      infected with a recombinant baculovirus carrying cDNA for the pro-alpha1(III)
      chain of type-III collagen. A high level of expression was obtained, and a small
      proportion of the heterologously expressed pro-alpha1(III) chains formed normally
      disulphide-bonded procollagen III, which was secreted into the culture medium.
      This species displayed a melting temperature (Tm) of approx. 38 degrees C as
      assessed by its resistance to digestion by a mixture of trypsin and chymotrypsin,
      slightly lower than that of 39.5 degrees C for procollagen III synthesized by
      cultured human dermal fibroblasts, and reflected a slight degree of under
      hydroxylation of prolyl residues. This is possibly a consequence of the lower
      incubation temperature of insect cells, or of an insufficiency of prolyl
      hydroxylase activity within them. A significant proportion of the expressed
      chains formed trimeric molecules of similar thermal stability containing an
      apparently full-length triple-helical region, but were not disulphide-bonded and
      not secreted. In addition to providing a source of recombinant human procollagen
      III, the system promises to be useful in the study of procollagen chain
      association and subsequent folding.

PMID- 8554531
TI  - DNA binding and methyl transfer catalysed by mouse DNA methyltransferase.
AB  - By using a purified fraction of mouse DNA methyltransferase we have shown, by gel
      retardation analysis, that the enzyme forms a low-affinity complex preferentially
      with hemimethylated DNA; the complexes formed with unmethylated or with fully
      methylated DNA are of even lower affinity, and only very weak interaction occurs
      with DNA lacking CG dinucleotides. Interaction is inhibited by N-ethylmaleimide.
      Methyl transfer from S-adenosyl-methionine is associated with the release of the
      fully methylated product from the complex. Complexes formed with the intact
      enzyme are extremely large, but limited trypsin treatment allows a major complex
      to enter the gel. DNA binding is not inhibited by this limited proteolysis of the
      native enzyme.

PMID- 8554532
TI  - The 4F2hc surface antigen is necessary for expression of system L-like neutral
      amino acid-transport activity in C6-BU-1 rat glioma cells: evidence from
      expression studies in Xenopus laevis oocytes.
AB  - Mammalian cells possess a variety of amino acid-transport systems with
      overlapping substrate specificity. System L is one of the major amino acid
      transport systems in all non-epithelial cells. Its molecular structure is not
      known. To clone the neutral amino acid-transporter system L, we followed an
      expression cloning strategy using Xenopus laevis oocytes. A cDNA library derived
      from C6-BU-1 rat glioma cells was used as a source, because high expression of
      system L activity could be demonstrated with polyadenylated RNA isolated from
      these cells, when injected into Xenopus laevis oocytes [Broer, Broer and
      Hamprecht (1994) Biochim. Biophys. Acta 1192, 95-100]. A single clone (ILAT) was
      identified, the sense cRNA of which, on injection into Xenopus laevis oocytes,
      stimulated sodium-independent isoleucine transport by about 100-fold. Further
      characterization revealed that transport of cationic amino acids was also
      stimulated. Sequencing of the cDNA showed that the identified clone is the heavy
      chain of the rat 4F2 surface antigen, a marker of tumour cells and activated
      lymphocytes. Uptake of neutral and cationic amino acids was not stimulated by the
      presence of Na+ ions. Antisense cRNA transcribed from this clone or antisense
      oligonucleotides, when co-injected with polyadenylated RNA from C6-BU-1 rat
      glioma cells, completely suppressed system L-like isoleucine-transport activity.
      We conclude that ILAT is necessary for expression of system L-like amino acid
      transport activity by polyadenylated RNA from C6-BU-1 rat glioma cells.

PMID- 8554534
TI  - Metabolization of iron by plant cells using O-Trensox, a high-affinity abiotic
      iron-chelating agent.
AB  - A synthetic siderophore, O-Trensox (L), has been designed and synthesized to
      improve iron nutrition of plants. The affinity for iron of this ligand [pFe(III)
      = 29.5 and pFe(II) = 17.9] is very high compared with EDTA. In spite of its high
      and specific affinity for iron, O-Trensox was found to be able to prevent, and to
      reverse, iron chlorosis in several plant species grown in axenic conditions. It
      also allows the iron nutrition and growth of Acer pseudoplatanus L. cell
      suspensions. The rate of iron metabolization was monitored by 59Fe radioiron.
      Ferritins, the iron storage proteins, are shown to be the first iron-labelled
      proteins during iron metabolization and to be able to further dispatch the metal.
      Using Fe(III)-Trensox, the rate of iron incorporation into ferritin was found to
      be higher than when using Fe-EDTA, but slower than with Fe-citrate, the natural
      iron carrier in xylem. During a plant cell culture, the extracellular
      concentrations of iron complex and free ligand were measured; changes in their
      relative amounts showed that the iron complex is dissociated extracellularly and
      that only iron is internalized. This suggests a high affinity for iron of a
      putative carrier on the plasmalemma. In contrast with Fe-citrate and Fe-EDTA
      complexes, Fe(III)-Trensox is not photoreducible. Its ability to induce radical
      damage as a Fenton reagent was tested using supercoiled DNA as target molecule.
      Unlike Fe-citrate and Fe-EDTA, Fe(II)-Trensox and Fe(III)-Trensox were proven to
      be harmless even during ascorbate-driven reduction, while Fe-EDTA and Fe-citrate
      generate heavy damage to DNA.

PMID- 8554533
TI  - Protein 4.1 is a component of the nuclear matrix of mammalian cells.
AB  - Protein 4.1 is a major component of the erythrocyte membrane skeleton that
      promotes the interaction of spectrin with actin and links the resulting complex
      network to integral membrane proteins. Here we analyse the distribution of
      different 4.1 proteins within the nucleus of mammalian cells. Nuclear matrices
      have been prepared from Madin-Darby canine kidney (MDCK) and HeLa cells and
      protein fractions isolated at each step of the purifications have been analysed
      by immunoblotting using characterized polyclonal antibodies against protein 4.1.
      Two 4.1 polypeptides of M(r) approximately 135,000 and 175,000 are extracted
      after DNase I digestion and 0.25 M ammonium sulphate treatments, suggesting that
      they may be associated with chromatin. Interestingly, nuclear matrices isolated
      after DNase I digestion and sequential treatments with increasing ionic strength
      contain a third 4.1 polypeptide of M(r) approximately 75,000 (4.1p75), suggesting
      that it is a component of the nuclear matrix. Immunoblot analyses of nuclear
      matrices isolated from different cell types and species indicate that 4.1p75 is a
      common element of the nuclear matrix of mammalian cells. Moreover, 4.1p75
      distributes to typical nuclear speckles which are enriched with the spliceosome
      assembly factor SC35, as revealed by double-label immunofluorescence analyses.
      Protein 4.1p75 might be an anchoring element of the nucleoskeleton, playing a
      role similar to that described for the erythroid protein 4.1 in red blood cells.

PMID- 8554535
TI  - Analysis of the mitochondrial ATP synthase beta-subunit gene in Drosophilidae:
      structure, transcriptional regulatory features and developmental pattern of
      expression in Drosophila melanogaster.
AB  - We have cloned and determined the structure of the gene encoding the H(+)-ATP
      synthase beta subunit in two distantly related Drosophila species, D.
      melanogaster and D. virilis. The gene contains three exons that are extremely
      well conserved at the amino acid level, not only in the region encoding the
      mature protein but also in that encoding the leader peptide. Primer extension
      analysis indicates that the 5' untranslated region is extremely short, and
      reveals the presence of multiple initiation sites of transcription in both
      Drosophila species. The promoters of D. melanogaster and D. virilis H(+)-ATP
      synthase beta-subunit genes contain a conserved region surrounding the initiation
      transcription sites. Nucleotide sequence analysis has revealed the absence of
      canonical TATA and CCAAT boxes and the presence of several putative regulatory
      elements in both promoter regions, including GAGA, GATA and Ets binding sites. We
      have analysed the pattern of gene expression during D. melanogaster development.
      The mRNA is stored in oocytes, and activation of transcription takes place after
      10 h of development. The expression of the nuclear-encoded H(+)-ATP synthase beta
      subunit is strictly coordinated with the expression of subunits 6 and 8 of the
      same complex that are encoded in the mitochondrial genome.

PMID- 8554537
TI  - Stereospecificity of inositol hexakisphosphate dephosphorylation by Paramecium
      phytase.
AB  - InsP6 is an abundant compound in many micro-organisms, plants and animal cells.
      Its function and route of synthesis are still largely unknown. Degradation of
      InsP6 is mediated by phytase, which in most organisms dephosphorylates InsP6 in a
      relatively non-specific way. In the micro-organism Paramecium, however, the
      enzyme has been shown to dephosphorylate InsP6 to InsP2 in a specific order, but
      its stereospecificity has not been established, i.e. the phosphates are removed
      in the sequence 6/5/4/3 or 6/5/4/1 or 4/5/6/1 or 4/5/6/3 [Freund, Mayr, Tietz and
      Schultz (1992) Eur. J. Biochem. 207, 359-367]. We have isolated the InsP4
      intermediate and identified its absolute configuration as D-Ins(1,2,3,4)P4.
      Furthermore, degradation of [3,5-32P]InsP6 yielded a 32P-labelled InsP2 isomer, D
      Ins(2,3)P2. These data demonstrate that Paramecium phytase removes the phosphates
      of InsP6 in the sequence 6/5/4/1. Knowing the stereochemical course of the
      enzyme, it can be used to elucidate the route of InsP6 synthesis, as it allows us
      to determine the specific radioactivity at individual positions of the molecular
      after pulse-labelling cells with [32P]P1 in vivo or [gamma-32P]ATP in vitro.

PMID- 8554536
TI  - Direct activation and anti-repression functions of GAL4-VP16 use distinct
      molecular mechanisms.
AB  - In order to determine whether the molecular mechanisms used for direct activation
      by GAL4-VP16 are the same as those used for anti-repression, we have employed
      monoclonal antibodies specific for the VP16 activation domain. In the absence of
      added repressors, GAL4-VP16 was able to stimulate transcription from a template
      containing GAL4-binding sites, and the antibodies raised against the VP16
      activation domain failed to inhibit this direct activation. GAL4-VP16 also was
      able to prevent histone H1-mediated repression by a mechanism that was strongly
      dependent on the presence of specific GAL4-binding elements in the promoter.
      However, in contrast to the assays conducted in the absence of repressors, the
      antibodies were strong inhibitors of GAL4-VP16-activated transcription in the
      presence of histone H1. Thus the binding of the antibodies distinguished between
      the direct activation and anti-repression functions of GAL4-VP16, indicating that
      these functions operate through distinct molecular mechanisms. The anti
      repression-specific mechanism that is inhibitable by the antibodies acted at an
      early stage of preinitiation complex formation. Deletions of individual
      subdomains of the VP16 activation domain demonstrated that there was not a
      discrete subdomain responsible for the anti-repression function of GAL4-VP16.
      Thus, the inhibitory effect of the antibodies appeared to be due to the location
      of the epitope within the activator protein rather than to some inherent
      biochemical property of that region of the protein that is required specifically
      for anti-repression. The inhibitory effect of the antibodies also ruled out the
      possibility that steric exclusion of repressor proteins from the promoter was the
      sole means of anti-repression by the transcriptional activator.

PMID- 8554538
TI  - Nucleus-associated phosphorylation of Ins(1,4,5)P3 to InsP6 in Dictyostelium.
AB  - Although many cells contain large amounts of InsP6, its metabolism and function
      is still largely unknown. In Dictyostelium lysates, the formation of InsP6 by
      sequential phosphorylation of inositol via Ins(3,4,6)P3 has been described
      [Stevens and Irvine (1990) Nature (London) 346, 580-583]; the second messenger
      Ins(1,4,5)P3 was excluded as a potential substrate or intermediate for InsP6
      formation. However, we observed that mutant cells labelled in vivo with
      [3H]inositol showed altered labelling of both [3H]Ins(1,4,5)P3 and [3H]InsP6. In
      this report we demonstrate that Ins(1,4,5)P3 is converted into InsP6 in vitro by
      nucleus-associated enzymes, in addition to the previously described stepwise
      phosphorylation of inositol to InsP6 that occurs in the cytosol. HPLC analysis
      indicates that Ins(1,4,5)P3 is converted into InsP6 via sequential
      phosphorylation at the 3-, 6- and 2-positions. Ins[32P]P6, isolated from cells
      briefly labelled with [32P]Pi, was analysed using Paramecium phytase, which
      removes the phosphates of InsP6 in a specific sequence. The 6-position contained
      significantly more 32P radioactivity than the 4- or 5-positions, indicating that
      the 6-position is phosphorylated after the other two positions. The results from
      these in vivo and in vitro experiments demonstrate a metabolic route involving
      the phosphorylation of Ins(1,4,5)P3 via Ins(1,3,4,5)P4 and Ins(1,3,4,5,6)P5 to
      InsP6 in a nucleus-associated fraction of Dictyostelium cells.

PMID- 8554539
TI  - Zn2+ depletion blocks endosome fusion.
AB  - Fusion among endosomes is an important step for transport and sorting of
      internalized macromolecules. Working in a cell-free system, we previously
      reported that endosome fusion requires cytosol and ATP, and is sensitive to N
      ethylmaleimide. Fusion is regulated by monomeric and heterotrimeric GTP-binding
      proteins. We now report that fusion can proceed at very low Ca2+ concentrations,
      i.e. < 30 nM. Moreover, fusion is not affected when intravesicular Ca2+ is
      depleted by preincubation of vesicles with calcium ionophores (5 microM ionomycin
      or A23187) in the presence of calcium chelators (5 mM EGTA or 60 mM EDTA). The
      results indicate that fusion can proceed at extremely low concentrations of
      intravesicular and extravesicular Ca2+. However, BAPTA [1,2-bis-(o
      aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid], a relatively specific Ca2+
      chelator, inhibits fusion. BAPTA binds other metals besides Ca2+. We present
      evidence that BAPTA inhibition is due not to Ca2+ chelation but to Zn2+
      depletion. TPEN [N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylenediamine], another
      metal-ion chelator with low affinity for Ca2+, also inhibited fusion. TPEN- and
      BAPTA-inhibited fusions were restored by addition of Zn2+. Zn(2+)-dependent
      fusion presents the same characteristics as control fusion. In intact cells, TPEN
      inhibited transport along the endocytic pathway. The results indicate that Zn2+
      depletion blocks endosome fusion, suggesting that this ion is necessary for the
      function of one or more factors involved in the fusion process.

PMID- 8554540
TI  - Cloning of the Schizosaccharomyces pombe gene encoding diadenosine 5',5"'-P1,P4
      tetraphosphate (Ap4A) asymmetrical hydrolase: sequence similarity with the
      histidine triad (HIT) protein family.
AB  - Diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) asymmetric hydrolase (EC 3.6.1.17)
      is a specific catabolic enzyme of Ap4A found in Schizosaccharomyces pombe. We
      have previously described the partial purification of Ap4A hydrolase from S.
      pombe [Robinson, de la Pena and Barnes (1993) Biochim. Biophys. Acta 1161, 139
      148]. We determined the sequence of the N-terminal 20 amino acids of Ap4A
      hydrolase and designed two degenerate PCR primers based on the sequence. The 60
      bp DNA fragment obtained by PCR, which is specific to Ap4A hydrolase, was used to
      isolate the Ap4A hydrolase gene, aph1, from S. pombe by screening a genomic DNA
      library in a multicopy plasmid. Ap4A hydrolase activity from the crude
      supernatant of a positive S. pombe transformant was about 25-fold higher than the
      control. There was no detectable stimulation of enzymic activity by phosphate.
      The aph1 gene from S. pombe contains three introns. The intron boundaries were
      confirmed by sequencing the cDNA of the aph1 gene from a S. pombe cDNA library.
      The deduced open reading frame of the aph1 gene codes for 182 amino acids. Two
      regions of significant local similarity were identified between the Ap4A
      hydrolase and the histidine triad (HIT) protein family [Seraphin (1992) DNA
      Sequence 3, 177-179]. HIT proteins are present in prokaryotes, yeast, plants and
      mammals. Their functions are unknown, except that the bovine protein inhibits
      protein kinase C in vitro. All four histidine residues which are conserved among
      the HIT proteins, including the HxHxH putative Zn(2+)-binding motif, are
      conserved in the Ap4A hydrolase. In addition, there are two regions of similarity
      between the Ap4A phosphorylases I and II from Saccharomyces cerevisiae and Ap4A
      hydrolase from S. pombe. These regions overlap with the HIT protein similarity
      regions. The aph1 gene from S. pombe is the first asymmetrical Ap4A hydrolase
      gene to be cloned and sequenced.

PMID- 8554541
TI  - Spermine uptake is necessary to induce haemoglobin synthesis in murine
      erythroleukaemia cells.
AB  - To determine whether intracellular uptake of spermine is necessary to induce
      haemoglobin synthesis in murine erythroleukaemia (MEL) DS 19 cells, we used
      single-step selection for resistance to N1,N12-bis(ethyl)spermine (BESM), a
      cytotoxic spermine analogue, to isolate clones deficient in polyamine transport.
      The cells were approximately 500-fold more resistant to BESM than parental cells
      and were unable to accumulate BESM, putrescine, spermidine or spermine. Addition
      of spermine to the polyamine-transport-deficient cells failed to induce
      haemoglobin synthesis. Hexamethylene-1,6-bisacetamide, a well-known
      differentiating agent, induced haemoglobin synthesis in both parental and
      resistant cells. Polyamine-transport-deficient cells transfected with DNA
      purified from the parental cell line were further selected for their ability to
      grow in the presence of alpha-difluoromethylornithine and putrescine. The
      transfectants had an active transport system for polyamines, and spermine added
      to their culture medium accumulated inside the cells and induced haemoglobin
      production. These findings indicate that intracellular spermine uptake is
      required to induce haemoglobin production in MEL cells.

PMID- 8554542
TI  - Expression of phosphatidylethanolamine N-methyltransferase-2 in McArdle-RH7777
      hepatoma cells inhibits the CDP-choline pathway for phosphatidylcholine
      biosynthesis via decreased gene expression of CTP:phosphocholine
      cytidylyltransferase.
AB  - Phosphatidylethanolamine N-methyltransferase-2 (PEMT2) of rat liver was expressed
      in McArdle-RH7777 rat hepatoma cells, which lack endogenous PEMT activity.
      Expression of the enzyme was confirmed by assay of PEMT activity and
      immunoblotting. There was no change in the amount of phosphatidylcholine in the
      transfected cells [Cu, Houweling and Vance (1994) J. Biol. Chem. 269, 24531
      24533], even though the expression of PEMT2 caused an increased incorporation of
      [methyl-3H]methionine and [3H]ethanolamine into phosphatidylcholine. In contrast,
      [3H]serine incorporation into phosphatidylcholine was only marginally enhanced by
      PEMT2 expression. Incorporation of [methyl-3H]choline into phosphatidylcholine
      was decreased by greater than 60%, suggesting that the CDP-choline pathway was
      inhibited as a result of PEMT2 expression. CTP:phosphocholine
      cytidylyltransferase (CT) activities in transfected cell lines were decreased in
      proportion to the level of expression of PEMT2. Immunoblot analyses showed a
      decrease in CT mass as a function of PEMT2 expression. In contrast, there was no
      change in the mass of protein disulphide-isomerase or the relative amounts of
      most proteins expressed in the PEMT2-transfected, compared with control, cells.
      Similarly, the expression of CT mRNA was decreased in PEMT2-expressing cells,
      whereas the mRNAs for protein disulphide-isomerase and actin were unchanged. When
      cell growth was slowed by incubating McArdle-RH7777 cells at 25 degrees C,
      compared with 37 degrees C, there was no difference in the specific activity of
      the CT. These results argue that PEMT2 expression down-regulates the CDP-choline
      pathway by decreasing the expression of the gene for the CT. The decreased
      activity of the CDP-choline pathway might contribute to the slower rate of cell
      division in PEMT2-transfected hepatoma cells.

PMID- 8554543
TI  - The suppression of the N-nitrosating reaction by chlorogenic acid.
AB  - N-Nitrosation of a model aromatic amine (2,3-diamino-naphthalene) by the N
      nitrosating agent produced by nitrite in acidic solution was inhibited by a
      polyphenol, chlorogenic acid, which is an ester of caffeic acid quinic acid.
      Caffeic acid also inhibited the N-nitrosation, but quinic acid did not. 1,2
      Benzenediols and 3,4-dihydroxybenzoic acid had inhibitory activities. Chlorogenic
      acid, caffeic acid, 1,2-benzenediols and 3,4-dihydroxybenzoic acid were able to
      scavenge the stable free radical, 1,1-diphenyl-2-picrylhydrazyl. Chlorogenic acid
      was found to be nitrated by acidic nitrite. The kinetic studies and the nitration
      observed only by bubbling of nitric oxide plus nitrogen dioxide gases indicated
      that the nitrating agent was nitrogen sesquioxide. The observations showed that
      the mechanism by which chlorogenic acid inhibited N-nitrosation of 2,3-diamino
      naphthalene is due to its ability to scavenge the nitrosating agent, nitrogen
      sesquioxide. Chlorogenic acid may be effective not only in protecting against
      oxidative damage but also in inhibiting potentially mutagenic and carcinogenic
      reactions in vivo.

PMID- 8554544
TI  - Ca2+ release triggered by nicotinate adenine dinucleotide phosphate in intact sea
      urchin eggs.
AB  - Nicotinate adenine dinucleotide phosphate (NAADP) was recently identified [Lee
      and Aarhus (1995) J. Biol. Chem. 270, 2152-2157; Chini, Beers and Dousa (1995) J.
      Biol. Chem. 270, 3116-3223] as a potent Ca(2+)-releasing agent in sea urchin egg
      homogenates. NAADP triggered Ca2+ release by a mechanism that was distinct from
      inositol 1,4,5-trisphosphate (InsP3)- and cyclic ADP-ribose (cADPR)-induced Ca2+
      release. When NAADP was microinjected into intact sea urchin eggs it induced a
      dose-dependent increase in cytoplasmic free Ca2+ which was independent of the
      extracellular [Ca2+]. The Ca2+ waves elicited by microinjections of NAADP
      originated at the site of injection and swept across the cytosol. As previously
      found in sea urchin egg homogenates, NAADP-induced Ca2+ release in intact eggs
      was not blocked by heparin or by prior desensitization to InsP3 or cADPR. Thio
      NADP, a specific inhibitor of the NAADP-induced Ca2+ release in sea urchin
      homogenates [Chini, Beers and Dousa (1995) J. Biol. Chem. 270, 3116-3223] blocked
      NAADP (but not InsP3 or cADPR) injection-induced Ca2+ release in intact sea
      urchin eggs. Finally, fertilization of sea urchin eggs abrogated subsequent NAADP
      induced Ca2+ release, suggesting that the NAADP-sensitive Ca2+ pool may
      participate in the fertilization response. This study demonstrates that NAADP
      acts as a selective Ca(2+)-releasing agonist in intact cells.

PMID- 8554545
TI  - Identification on melanoma cells of p39, a cysteine proteinase that cleaves C3,
      the third component of complement: amino-acid-sequence identities with
      procathepsin L.
AB  - We previously identified, on normal or tumour cells, two membrane proteinases,
      p57 and p65, that cleave human C3, the third component of complement, thus
      regulating C3's biological properties. Whereas p57 was purified from human
      erythrocytes, p65 was identified using polyclonal anti-p57 antibodies on a human
      melanoma cell line resistant to complement lysis. Analysis of cell distribution
      of C3-cleaving proteinases established that DSm, a murine melanoma cell line,
      expressed a C3-cleaving proteinase distinct from p57 and p65 proteinases. Thus we
      purified the C3-cleaving proteinase solubilized from membranes of DSm cells. The
      purified proteinase, termed 'p39' on the basis of its molecular mass of 39 kDa,
      was identified, using specific proteinase inhibitors, as a cysteine proteinase.
      Anti-p39 antibodies, prepared against highly purified p39, localized the p39 C3
      cleaving proteinase mainly at the cell surface and demonstrated that p39 is also
      secreted. Anti-p39 antibodies inhibited solubilized C3-cleaving activity.
      Preincubation of DSm cells with anti-p39 F(ab')2 fragments increased up to 60%
      complement cell susceptibility. Amino acid analysis of N-terminal and three other
      regions of p39 demonstrated that this C3-cleaving proteinase carries 100%
      identity within four regions of procathepsin L. This is the first demonstration
      that a melanoma cell line expresses on its surface and secretes a p39 C3-cleaving
      cysteine proteinase that shares sequence identities with procathepsin L. Thus the
      p39 cysteine proteinase represents a new member of the C3-cleaving proteinase
      family associated with, and/or expressed on, the cell surface.

PMID- 8554546
TI  - Catalytic consequences of experimental evolution: catalysis by a 'third
      generation' evolvant of the second beta-galactosidase of Escherichia coli,
      ebgabcde, and by ebgabcd, a 'second-generation' evolvant containing two
      supposedly 'kinetically silent' mutations.
AB  - The kinetics of hydrolysis of a series of synthetic substrates by two
      experimentally evolved forms ('evolvants'), ebgabcd and ebgabcde, of the second
      beta-galactosidase of Escherichia coli have been measured. The ebgabcd enzyme
      differs from the wild-type (ebgo) enzyme by Asp92-->Asn (a) and Trp977-->Cys (b)
      changes in the large subunit, as well as two changes hitherto considered to have
      no kinetic effect, Ser979-->Gly in the large subunit (c) and Glu122-->Gly in the
      small subunit (d). The enzyme ebgabcde contains in addition a Glu93-->Lys change
      in the large subunit (e). Comparison of ebgabcd with ebgab [Elliott, K, Sinnott,
      Smith, Bommuswamy, Guo, Hall and Zhang (1992) Biochem. J. 282, 155-164] indicates
      that the c and d changes in fact accelerate the hydrolysis of the glycosyl-enzyme
      intermediate by a factor of 2.5, and also decrease the charge on the aglycone
      oxygen atom at the first transition state; the charge on the glycone, however, is
      unaltered [see K, Konstantinidis, Sinnott and Hall (1993) Biochem. J. 291, 15
      17]. The e mutation causes a fall in the degalactosylation rate of about a factor
      of 3, and its occurrence only together with c and d mutations [Hall, Betts and
      Wootton (1989) Genetics 123, 635-648] suggests that degalactosylation of a
      hypothetical ebgabe enzyme would be so slow that the enzyme would have no
      biological advantage over the ancestral ebgab. The transfer products from
      galactosyl-ebgabcd and galactosyl-ebgabcde to high concentrations to glucose have
      been measured; the predominant product is allolactose, but significant quantities
      of lactose are also formed; however, at apparent kinetic saturation of the
      galactosyl-enzyme, hydrolysis rather than transfer is the preponderant pathway. A
      knowledge of the rates of enzyme-catalysed exchange of 18O from [1-18O]galactose
      to water permits the construction of the free-energy profiles for hydrolysis of
      lactose by begabcd and ebgabcde. As with the other evolvants, changes in the
      profile away from the rate-determining transition state are essentially random,
      and there is no correlation between the changes in the free energies of
      intermediates and of their flanking transition states. We consider the aggregate
      of our kinetic data on the ebg system to be telling experimental support for the
      theoretical objections of Pettersson [Pettersson (1992) Eur. J. Biochem. 206, 289
      295 and previous papers] to the Albery-Knowles theory of the evolution of enzyme
      kinetic activity.

PMID- 8554547
TI  - Investigation of the active site of oligosaccharyltransferase from pig liver
      using synthetic tripeptides as tools.
AB  - Oligosaccharyltransferase (OST), an integral component of the endoplasmic
      reticulum membrane, catalyses the transfer of dolichyl diphosphate-linked
      oligosaccharides to specific asparagine residues forming part of the Asn-Xaa
      Thr/Ser sequence. We have studied the binding and catalytic properties of the
      enzyme from pig liver using peptide analogues derived from the acceptor peptide N
      benzoyl-Asn-Gly-Thr-NHCH3 by replacing either asparagine or threonine with amino
      acids differing in size, stereochemistry, polarity and ionic properties. Acceptor
      studies showed that analogues of asparagine and threonine with bulkier side
      chains impaired recognition by OST. Reduction of the beta-amide carbonyl group of
      asparagine yielded a derivative that, although not glycosylated, was strongly
      inhibitory (50% inhibition at approximately 140 microM). This inhibition may be
      due to ion-pair formation involving the NH3+ group and a negatively charged base
      at the active site. Hydroxylation of asparagine at the beta-C position increased
      Km and decreased Vmax, indicating an effect on both binding and catalysis. The
      threo configuration at the beta-C atom of the hydroxyamino acid was essential for
      substrate binding. A peptide derivative obtained by replacement of the threonine
      beta-hydroxy group with an NH2 group was found to display acceptor activity. This
      shows that the primary amine is able to mimic the hydroxy group during
      transglycosylation. The pH optimum with this derivative is shifted by
      approximately 1 pH unit towards the basic region, indicating that the neutral NH2
      group is the reactive species. The various data are discussed in terms of the
      catalytic mechanism of OST, particular emphasis being placed on the role of
      threonine/serine in increasing the nucleophilicity of the beta-amide of
      asparagine through hydrogen-binding.

PMID- 8554548
TI  - Inhibition of autophagic proteolysis by cell swelling in hepatocytes.

PMID- 8554549
TI  - Cell hydration and proteolysis control in liver.

PMID- 8554550
TI  - Establishment of immortal hepatocytes from a CYP3A7-transgenic/p53-knockout
      mouse.
AB  - Immortal hepatocytes were established from a CYP3A7-transgenic/p53-knockout
      mouse. The cells could be maintained with shorter doubling time after culture for
      1 month. Detectable amounts of CYP3A7 mRNA and the activity of 7-propoxycoumarin
      O-depropylase, one of the representative CYP3A activities, were present in the
      immortal hepatocytes. Albumin mRNA, which is specifically expressed in the liver,
      remained in these cells.

PMID- 8554551
TI  - Mucin genes are regulated by estrogen and dexamethasone.
AB  - This study demonstrates for the first time that mucin gene expression can be
      significantly up-regulated by steroid hormones. The effects of estrogen,
      progesterone and dexamethasone on the expression of three mucin genes, MUC1, MUC4
      and MUC5c were determined in a human epithelial cell line. This cell line
      secretes mucin and contains steroid receptors. Steady-state mRNA levels were
      quantified by slot blot hybridization using radiolabelled oligonucleotide probes.
      Normally, these genes (originally isolated from airways) are expressed at low
      constitutive levels. However, steady state levels of MUC4 and MUC5c mRNA were up
      regulated at least 3-4 fold by estrogen supplementation, and 1.5-2 fold by
      dexamethasone. MUC1 mRNA levels were minimally affected. Progesterone
      supplementation had no effect but was able to interfere with the up-regulation by
      estrogen. The mechanism of regulation remains to be determined but may be
      transcriptional. However, steroids have been shown to control gene expression at
      several different levels.

PMID- 8554552
TI  - Rat PPAR delta contains a CGG triplet repeat and is prominently expressed in the
      thalamic nuclei.
AB  - We have isolated a new rat sequence containing motifs of a nuclear hormone
      receptor from a brain cDNA library. The deduced amino acid sequence encoded by
      the cDNA clone showed a strong homology to the human NUCI and the mouse
      peroxisome proliferator activated receptor delta (PPAR delta). We therefore refer
      to this new clone as rat PPAR delta (rPPAR delta). The new feature of rPPAR delta
      is a 14 CGG triplet repeat on the 5' untranslated region, not previously reported
      in either NUCI or mPPAR delta. We found that rPPAR delta was expressed as a 3.5
      kb transcript which showed a wide distribution in adult rat tissues. Abundant
      expression was detected in brain, heart, skeletal muscle, kidney and lung. Weaker
      expression was noted in the liver, spleen and testis. To determine the specific
      brain localization of rPPAR delta we performed in situ hybridization analysis.
      Prominent expression was observed in the thalamus, particularly in the posterior
      part of the ventral medial nucleus, a site responsive to pain and cold stress.
      These results raise the possibility that PPAR delta might play a role in
      modulating response to thermal and pain sensations.

PMID- 8554553
TI  - Endogenous retinoids in the early avian embryo.
AB  - Vitamin A is required to rescue the vitamin A-deficient quail embryo from early
      death, but the endogenous presence of bioactive retinoids has not been documented
      in these embryos. The analysis of 2000 pooled stage 5-8 normal quail embryos
      described here provides for the first time direct evidence for the presence of
      endogenous all-trans-retinoic acid (5 nM) and 3,4-didehydroretinoic acid (4 nM),
      signaling molecules known to be potent ligands for nuclear retinoic acid
      receptors. The demonstration of all-trans-retinal (80 nM), all-trans-retinol (100
      nM), 3,4-didehydroretinol (200 nM), and retinyl esters (100 nM) suggests the
      capability of the early avian embryo to generate in situ the vitamin A-bioactive
      molecules required for development. Analysis of 2100 pooled stage 5-8 quail
      embryos from vitamin A-deficient eggs revealed no vitamin A-like molecules,
      supporting the evidence that links vitamin A deficiency in these embryos to
      abnormalities and early death.

PMID- 8554554
TI  - Activation by heat shock of hsp70 gene transcription in sea urchin embryos.
AB  - We had previously shown that P. lividus embryos subjected to heat shock are
      unable to synthesize proteins of the hsp70 family at a detectable level before
      the hatching blastula stage. We show here that this is not due to the inability
      to synthesize the hsp70 mRNAs, which are detectable following heat shock also in
      early stages, although in much lower amounts per embryo than in later stages.
      These mRNAs are also translated, as judged by the facts that they are present in
      the polysomal pellet, and that they are translatable in a cell free system. As to
      the question of the amount of hsp70 RNAs per nucleus, we conclude that this is
      also higher in later than in earlier stages. The presence of hsp70 mRNAs is
      already detectable after heating at 4 centigrades above 20 and their amount
      increases with the increase of temperature in the range between 24 degrees C and
      28 degrees C.

PMID- 8554555
TI  - pp60c-src increases voltage-operated calcium channel currents in vascular smooth
      muscle cells.
AB  - Intracellular application of pp60c-src, a nonreceptor tyrosine kinase present in
      large amounts in smooth muscle cells increased voltage-operated calcium channel
      currents in rabbit ear artery cells. Intracellular peptide-A, an inhibitor of
      pp60c-src, reduced calcium channel currents and abolished the action of pp60c
      src. Selective tyrosine kinase inhibitors, tyrphostin-23 and genistein also
      abolished the effect of pp60c-src, but inhibition of protein kinase C did not
      prevent the action of pp60c-src. These results suggest that endogenous pp60c-src
      modulates voltage-operated calcium channels by a mechanism dependent on tyrosine
      phosphorylation but not involving activation of protein kinase C.

PMID- 8554556
TI  - Characterization of a protein that binds a negative regulatory element in the
      mammary-specific whey acidic protein promoter.
AB  - Whey Acidic Protein (WAP) gene expression is restricted to the pregnant and
      lactating mammary gland. We have recently defined a negative regulatory element
      (NRE) in the WAP promoter which interacts with a factor (NBF) present in all
      nonWAP expressing cells (Kolb et al., 1994; J. Cell. Biochem. 56:245-261). Here
      we characterise this factor and show that although it is not related to a number
      of known transcription factors, including AP-1, NF-1 and SP-1, it may also be
      involved in controlling the expression from the mouse mammary tumour virus
      promoter. Three proteins that bind to the WAP-NRE have been identified, one of
      which is a 53kDa nuclear protein. This protein is present in nonWAP expressing
      cells, suggesting that it is responsible for limiting WAP expression to the
      pregnant and lactating mammary gland. This protein has been partially purified
      and its binding to the WAP-NRE is not appreciably affected by high salt
      concentrations.

PMID- 8554557
TI  - Molecular cloning of an isoform of Doc2 having two C2-like domains.
AB  - We previously isolated a novel protein having two C2-like domains known to
      interact with Ca2+ and phospholipid, and named Doc2 (Double C2). Doc2 is
      predominantly expressed in brain and is implicated in Ca(2+)-dependent
      neurotransmitter release. We have isolated here an isoform of Doc2 and named the
      original one Doc2 alpha and the new one Doc2 beta. Doc2 beta alsp has two C2-like
      domains and is 61% identical to Doc2 alpha at the amino acid level. In contrast
      to Doc2 alpha, the Doc2 beta mRNA is expressed ubiquitously. These results
      indicate that there are at least two isoforms of Doc2, and suggest that Doc2 beta
      is involved in Ca(2+)-dependent intracellular vesicle trafficking in various
      types of cells.

PMID- 8554558
TI  - Induction of tyrosine phosphorylation and translocation of ezrin by hepatocyte
      growth factor/scatter factor.
AB  - Ezrin is a member of the TERM family and is a key protein in cytoplasmic membrane
      cytoskeleton interactions. This study showed that hepatocyte growth
      factor/scatter factor (HGF/SF), a cytokine known to regulate motility,
      morphogenesis and growth of cells, stimulated the tyrosine phosphorylation of
      ezrin in a human colon epithelial cell line, HT115. After HGF/SF stimulation,
      ezrin translocated from the cytosol and generalised membrane to the areas of
      ruffled membrane as visualised by indirect immunofluorescent and immunogold
      electron microscopy. This effect was inhibited by genistein, a tyrosine kinase
      inhibitor. It is concluded that HGF/SF induces ezrin translocation by stimulation
      of its tyrosine phosphorylation and that this plays a key role in HGF/SF induced
      membrane ruffling.

PMID- 8554559
TI  - Lactacystin, a specific inhibitor of the proteasome, induces apoptosis in human
      monoblast U937 cells.
AB  - Lactacystin, originally isolated from a microbe as an inducer of neuritogenesis,
      targets the catalytic beta-subunit of the proteasome, and arrests the cell cycle.
      Here we report for the first time that lactacystin induces apoptotic cell death
      in human monoblastic U937 cells. When U937 cells were cultured with lactacystin,
      their nuclei were shrunken, a morphological change typical of apoptosis, and cell
      viability was decreased. Electrophoretic analysis revealed that chromosomal DNAs
      from lactacystin-treated cells were cleaved in an internucleosomal ladder-like
      pattern, indicating that cell death occurs through an apoptotic process, which
      was also confirmed by DNA fragmentation analysis using flow cytometry. These
      findings suggest that inhibition of the proteasome during proliferation results
      in apoptotic cell death, and that the proteasome is a key enzyme in the course of
      the cell cycle that destines the cell to proliferate, differentiate or die.

PMID- 8554560
TI  - Molecular cloning and expression of a guinea pig 3-hydroxysteroid
      sulfotransferase distinct from chiral-specific 3 alpha-hydroxysteroid
      sulfotransferase.
AB  - A guinea pig adrenal hydroxysteroid sulfotransferase (gpHST2) has been cloned
      that is distinct from guinea pig hydroxysteroid sulfotransferase that
      stereoselectively acts on 3 alpha-hydroxylated neutral steroids (gp3 alpha HST,
      redesignated gpHST1). The deduced amino acid sequences for gpHST1 and gpHST2 are
      86% identical; however, whereas gpHST1 selectively acts on 3 alpha-hydroxylated
      steroids, gpHST2 demonstrates a clear preference (but not exclusive specificity)
      for 3 beta-hydroxylated steroids suggesting that gpHST2 is similar to a
      previously reported guinea pig hydroxysteroid sulfotransferase that selectively
      acts on 3 beta-hydroxylated neutral steroids (gp3 beta HST). Additionally, gpHST2
      (33K) is the same size as gp3 beta HST and larger than gpHST1 (32K), contains
      amino acid sequences identical to peptides obtained from gp3 beta HST and cross
      reacts with antibodies raised against purified gp3 beta HST. Nonetheless, gpHST2
      can sulfonate both 3 alpha- and 3 beta-hydroxylated neutral steroids, suggesting
      that either gp3 beta HST does not have the exquisite stereoselectivity previously
      indicated or this subfamily of hydroxysteroid sulfotransferases is larger than
      originally thought.

PMID- 8554562
TI  - mt-mRNA stability regulates the expression of the mitochondrial genome during
      liver development.
AB  - We have recently reported that regulation of the expression of the nuclear
      encoded beta-F1-ATPase gene during development of rat liver is exerted also by
      the control of beta-F1-ATPase mRNA decay (Izquierdo, J.M., Ricart, J., Ostronoff,
      L.K., Egea, G. and Cuezva, J.M. (1995) J. Biol. Chem. 270, 10342-10350). In this
      paper, we report that high steady-state levels of the mitochondrial encoded mRNAs
      for subunits of the ATP synthase (ATP 6-8) in developing liver result from
      profound changes in the stability of the mitochondrial transcripts. The results
      strongly suggest that developmental regulation of nuclear and mitochondrial genes
      during biogenesis of mammalian mitochondria is concertedly controlled by a
      posttranscriptional mechanism that involves the regulation of mRNA degradation of
      both genomes.

PMID- 8554561
TI  - Thyroid hormone regulation of gene expression of the pituitary growth hormone
      releasing factor receptor.
AB  - To examine thyroid hormone regulation of the pituitary receptor for hypothalamic
      growth hormone (GH)-releasing factor (GRF), we studied effects of hypothyroidism
      on the pituitary GRF receptor (GRF-R) mRNA and its related parameters in rats.
      Thyroidectomy (Tx) induced a 61-65% reduction in GRF-R mRNA levels, which was
      significantly reversed with thyroxine (T4) replacement for 5 days at a dose of 1
      microgram/100 g/day. Pituitary GH contents changed parallel to GRF-R mRNA levels
      following the Tx and T4 replacement. In contrast, Tx enhanced GRF release > 2
      fold, which was not reversed with the regime of T4 replacement. These results
      indicate that thyroid hormone promotes pituitary GRF-R gene expression, not by
      modulating GRF secretion, but by acting on the pituitary directly. The decline in
      GRF receptor expression would contribute to somatotroph failure by rendering the
      pituitary refractory to the increased GRF signal in hypothyroidism.

PMID- 8554563
TI  - (Ca+Mg)ATPase and calcium influx in erythrocytes of patients with idiopathic
      hypercalciuria.
AB  - Increased erythrocyte (Ca+Mg)ATPase activity was previously observed in
      idiopathic hypercalciuria. In order to verify if this alteration is a primary or
      a secondary event, we studied Sr influx in erythrocytes from subjects with
      idiopathic hypercalciuria. (Ca+Mg)ATPase activity was significantly higher in
      hypercalciuric than in hypercalciuric than in normocalciuric subjects whereas no
      difference in Sr influx was found between the two groups. (Ca+Mg)ATPase activity
      positively correlated with the erythrocyte Sr content found after 5 min of
      incubation and with urine Ca excretion. The normal Sr permeability suggests that
      (Ca+Mg)ATPase is primarily altered in idiopathic hypercalciuria. The primary
      increase of (Ca+Mg)ATPase activity may enhance passive Ca influx by reduction of
      cellular Ca concentration. It may induce a defect in cellular Ca metabolism that
      may cause idiopathic hypercalciuria by stimulating bone Ca turn-over and enteral
      Ca absorption.

PMID- 8554564
TI  - Down-regulation by progesterone of CFTR expression in endometrial epithelial
      cells: a study by competitive RT-PCR.
AB  - To determine the effect of progesterone on the CFTR mRNA level in glandular
      epithelial cells of guinea-pig endometrium, a competitive RT-PCR was developed
      using an an internal standard a competitor with the same sequence as CFTR RNA
      except for a 20 nucleotide insertion. Using this method, the results showed that
      the CFTR mRNA level decreased in cells treated with estradiol plus progesterone
      compared to cells receiving estradiol alone. The decrease in CFTR mRNA level was
      maximal at 12 h incubation and was 27.3% of the CFTR mRNA level in estradiol
      treated cells. The effect of progesterone was mimicked by the progestagen, R5020
      and was inhibited by antiprogestins, RU 38,486 and ZK 98,299. Results are
      discussed in relation to the changes taking place in the endometrium in
      preparation for implantation of the embryo.

PMID- 8554565
TI  - Molecular cloning of a novel high molecular weight mucin (MG1) from human
      sublingual gland.
AB  - A human sublingual gland cDNA library was screened with a polyclonal antiserum
      against deglycosylated MG1 and a positive clone, pSM2-1, was isolated which codes
      for 196 amino acids in the carboxyl-terminal region of this mucin. This region is
      cysteine-rich and contains a C2-like domain upstream of the extreme carboxyl
      terminal domain in which the arrangement of cysteines is nearly identical to that
      in human von Willebrand factor, human intestinal mucin MUC2, human
      tracheobronchial mucin MUC5 and porcine and bovine submaxillary gland mucins.
      Northern analyses with pSM2-1 showed MG1 transcripts are abundant in sublingual
      gland and barely detectable in submandibular gland. This study provides the first
      primary sequence data on human salivary mucin MG1 and the significance of the
      results is discussed with respect to the biosynthesis and differential expression
      of MG1 in human salivary glands.

PMID- 8554566
TI  - Polyprotein processing in echovirus 22: a first assessment.
AB  - The major steps of the polyprotein processing of Echovirus 22 (EV22), a highly
      unusual member of the picornavirus family, have been characterized for the first
      time by employing in vitro assay systems. Cell-free expression of a P1-2ABC
      precursor as well as VP1-2A yielded autoproteolytically inactive proteins,
      suggesting that the 2A region of the EV22 polyprotein does not contain a
      proteolytic activity. The intra- and intermolecular cleavage specificity of
      proteinase 3C, the major proteolytic enzyme in picornaviruses, was studied by
      expressing the enzyme of EV22 in a bacterial system as well as in the framework
      of precursor molecules generated by in vitro transcription/translation in a cell
      free system. A VP1-2A percursor could very efficiently be cleaved in trans by the
      recombinant 3C, whereas the junction between P2 and P3 remained uncleaved.
      Expression of the complete P3-region in the cell-free system led to the
      autocatalytic release of large amounts of p22, a protein of the predicted
      molecular weight of the EV22 proteinase 3C that was recognized by an antibody
      raised against the recombinant enzyme.

PMID- 8554567
TI  - A serum mannose-binding lectin mediates complement-dependent lysis of influenza
      virus-infected cells.
AB  - The mechanism of lysis of influenza virus-infected BHK-21 cells by guinea pig
      serum (GPS) was investigated. Lysis was shown to involve activation of the
      classical complement pathway and was dependent on the presence of a mannose
      binding lectin in GPS. FACS analysis demonstrated Ca(2+)-dependent binding of the
      lectin to influenza virus-infected, but not uninfected, cells. Cells infected
      with mutant strains of virus lacking a particular high-mannose oligosaccharide at
      the tip of the hemagglutinin molecule showed reduced binding of the lectin and
      were correspondingly less sensitive to lysis by GPS than cells infected with the
      parent viruses. The degree or pattern of glycosylation of influenza viruses thus
      influences susceptibility to this mechanism of viral clearance. By interfering
      with the infectious process, lectin-dependent complement-mediated lysis of
      infected cells may be an important component of innate immunity to influenza and
      other enveloped viruses.

PMID- 8554568
TI  - cDNA cloning of three new forms of rat brain cytochrome P450 belonging to the
      CYP4F subfamily.
AB  - Three cDNA clones, designated 4f-8, 4f-34 and 4f-41, coding for three new forms
      of cytochrome P450 belonging to the CYP4F subfamily were isolated from an
      untreated rat brain cDNA library. cDNA 4f-8, 4f-34 and 4f-41 coded for proteins
      of 522, 526 and 537 amino acids, respectively, and their amino acid sequence
      similarity to CYP4F1 ranged from 71 to 80%. These new P450s were thus named
      CYP4F4, 4F5 and 4F6, respectively. Northern blot analysis revealed that the
      expression levels of these forms of P450 in the brain were somewhat low and that
      similar forms of subfamily 4F P450 were expressed in liver and kidney at a
      relatively high level compared with brain. No CYP4A expression was detected by
      Northern blot analysis in untreated rat brain mRNA. All three clones were in
      vitro-translatable using a reticulocyte lysate system. These results show that
      multiple forms of subfamily 4F P450 exist in the brain and that the subfamily 4F
      P450 may be one of the major forms of P450 in the brain.

PMID- 8554569
TI  - The L-selectin antibody FMC46 mediates rapid, transient increase in intracellular
      calcium in human peripheral blood mononuclear cells and Daudi lymphoma cells.
AB  - We report the induction of intracellular calcium mobilization [Ca2+]i in normal
      peripheral blood mononuclear cells (PBMC) and Daudi cells following binding with
      the L-selectin monoclonal antibody FMC46. The [Ca2+]i signal was mediated
      directly by binding of FMC46 without cross-linking antibodies. Increased [Ca2+]i
      was not induced by other L-selectin antibodies tested (TQ1, Leu8, Lam1.3). The
      increase in [Ca2+]i was rapid and was blocked completely by BAPTA, an agent which
      chelates intracellular calcium. The increase in [Ca2+]i was observed in calcium
      containing as well as calcium free medium, suggesting that FMC46 caused release
      of Ca2+ from intracellular stores. In both PBMC and Daudi cells, previous
      signaling via L-selectin still allowed signaling through cross-linking of surface
      antigen receptor. These data provide evidence for direct alteration of the state
      of lymphocytes after ligation of a specific L-selectin epitope. L-selectin
      mediated signaling does not desensitize signaling through the antigen-receptor
      and could therefore play a role in preactivating lymphocytes during endothelial
      transmigration into lymphoid tissues.

PMID- 8554570
TI  - Nonideality of water-hexafluoropropanol mixtures as studied by X-ray small angle
      scattering.
AB  - Strong temperature dependent low angle X-ray scattering by trifluoroethanol- and
      hexafluoro-2-propanol-water mixtures was observed in conditions commonly used in
      NMR work on peptides. At least two types of molecular effects may contribute to
      the observed scattering: formation of clathrate hydrate-like aggregates of
      alcohol with water as have been proposed for the similar system tert-butanol
      water (Iwasaki, K. and Fujiyama, T. (1976) J. Phys. Chem. 81, 1908-1912) and a
      further heterogeneity of the solution resulting from immiscibility of the two
      components.

PMID- 8554571
TI  - A novel mutation substituting tryptophan with arginine in the carboxyl-terminal,
      non-collagenous domain of collagen X in a case of Schmid metaphyseal
      chondrodysplasia.
AB  - A novel nucleotide change in the collagen X gene was identified in a Japanese
      family with Schmid metaphyseal chondrodysplasia (SMCD). The T to C change at
      nucleotide 1951 resulted in replacement of tryptophan by arginine at residue 651
      (W651R). This missense mutation is considered to be responsible for SMCD because
      1, the same mutation was not be identified in the collagen X gene from normal
      individuals; 2, the mutation segregated with the SMCD phenotype in the index
      family; 3, the substituted amino acid is highly conserved in type X collagens,
      and 4, the mutation causes a marked change in the hydrophobicity profile of the
      surrounding region in the NC1 domain. This novel mutation (W651) seems to have
      the same impact on bone development as W651X mutation.

PMID- 8554572
TI  - Activation of calcium-sensitive potassium channels in L6 skeletal myocytes by
      arginine vasopressin requires extracellular calcium.
AB  - The effects of extracellular application of arginine vasopressin (AVP) upon
      membrane currents in L6 skeletal myocytes was investigated using the whole-cell
      configuration of the patch-clamp technique. At 0 mV AVP produced large amplitude,
      transient outward currents that reversed when the clamping potential was changed
      to -100 mV (negative to EK). The effects of alterations in the extracellular K+
      concentration upon the current reversal potential suggested that the current
      elicited by AVP was carried mainly by K+ ions. Intracellular dialysis with 10
      microM inositol 1,4,5-trisphosphate (InsP3) elicited similar currents but only in
      6/14 cells. Inclusion of 5 mg ml-1 heparin in the intracellular solutions was
      ineffective at inhibiting the current responses to AVP. The AVP-induced current
      was totally abolished when the intracellular EGTA concentration was increased
      from 0.05 mM to 10 mM or Ca2+ was removed from the extracellular perfusing
      solution. These results suggest that AVP produces activation of a Ca(2+)
      sensitive K+ conductance in L6 skeletal myocytes by a process dependent upon
      extracellular Ca2+ and not intracellular Ca2+ release.

PMID- 8554573
TI  - Tumorigenicity and gene amplification potentials of cyclin D1-overexpressing
      NIH3T3 cells.
AB  - Cyclin D1 is a key regulator of the G1-S transition in cell cycle, and its gene
      is amplified and overexpressed in many cancers. To address the gene amplification
      potential of the cells in which the cyclin D1 gene expression is deregulated, we
      have established NIH3T3 clones with various levels of cyclin D1 transgene
      message. Those transfectants showed anchorage independent growth and
      tumorigenicity without in vitro morphological transformation. The degree of the
      transformed phenotype apparently correlated with the cyclin D1 expression level.
      Upon selection by N-(phosphonoacetyl)-L-aspartate (PALA), the cyclin D1
      transfected NIH3T3 cells showed a higher ability to develop PALA-resistant
      colonies by amplifying the CAD gene, as compared to the parental NIH3T3 cells.

PMID- 8554574
TI  - P-azidoiodoacetanilide, a new short photocrosslinker that has greater cysteine
      specificity than p-azidophenacyl bromide and p-azidobromoacetanilide.
AB  - An important criterion for a protein modifying agent is its residue selectivity.
      We report the synthesis of a new photocrosslinking agent, p-azidoiodoacetanilide
      (AIA), which has a greater specificity to modify cysteine residues than the
      widely used p-azidophenacyl bromide (APB). Crosslinking of UmuD protein, which
      only has one cysteine, in the homodimer using APB or AIA resulted in 39% and 30%
      crosslinking, respectively; however, crosslinking of UmuD/C24A, a derivative with
      no cysteines, resulted in 16% crosslinked dimer using APB but only 2% using AIA.
      In addition, incorporation of [2-14C]APB into UmuD/C24A was 43% the amount of
      incorporation into wildtype UmuD, whereas incorporation of [2-14C]AIA into
      UmuD/C24A was only 13% the amount incorporated into wildtype UmuD. We also
      examined the cysteine specificity of p-azidobromoacetanilide (ABA) and found it
      to be less cysteine specific than AIA.

PMID- 8554575
TI  - Identification of actin as a substrate of ICE and an ICE-like protease and
      involvement of an ICE-like protease but not ICE in VP-16-induced U937 apoptosis.
AB  - Human leukemia U937 cells are induced to undergo apoptosis by several
      chemotherapeutic agents; however, the cellular components involved in the process
      have not yet been identified. We found that an actin-cleavage activity (ACA) was
      activated in the VP-16-treated U937 cytosolic fraction and 15K- and 30K-actin
      fragments were produced. This ACA was inhibited by inhibitors of interleukin-1
      beta-converting enzyme (ICE)/ced-3 family proteases, such as Z-Asp-CH2-DCB, YVAD
      CHO, TPCK, TLCK, and iodoacetamide. Differing from ICE, the ACA could not process
      pro-IL-1 beta to mature IL-1 beta. Although ICE can cleave actin in vitro, ICE
      activity was not activated in the VP-16 treated U937 cells. These results
      indicate that actin is a potential substrate of ICE and ICE-like proteases, and
      that VP-16 preferentially activate an ICE-like protease, but not ICE itself, in
      U937 cells.

PMID- 8554576
TI  - Specific inhibition of apoptosis after cerebral hypoxia-ischaemia by moderate
      post-insult hypothermia.
AB  - In piglets studied on the first day of life transient hypoxia-ischaemia caused an
      increase in the fractions of necrotic and apoptotic cells in the cingulate sulcus
      compared to sham-operated controls. In animals subjected to the same hypoxic
      ischaemic insult but cooled to 34.9 degrees C (mean tympanic membrane
      temperature) for 12 hours commencing after resuscitation the fraction of cells
      undergoing necrosis was unchanged and comparable to that in animals which were
      not cooled. However, the fraction of apoptotic cells was reduced and was similar
      to that in sham-operated controls. Thus hypothermia specifically inhibited
      apoptosis. This result has implications for understanding the mechanisms of
      delayed cerebral injury and for the use of hypothermia as a neural rescue
      strategy in the developing brain.

PMID- 8554577
TI  - The secondary structure of phospholamban: a two-dimensional NMR study.
AB  - Phospholamban (PLN) is an intrinsic membrane protein of 52 amino acids which
      regulates the Ca2+ pump of the sarcoplasmic reticulum of heart, slow-twitch and
      smooth muscle (SR): it is normally assumed to exist in the membrane as a
      homopentamer. A monomeric analogue of phospholamban PLN(C41F), in which Cys41 was
      replaced by a Phe, was synthesized and its conformation studied by 1H NMR
      spectroscopy in a 1:1 mixture of chloroform/methanol. Most of the resonances in
      the 1H NMR spectra were assigned. The work has shown that the C-terminal
      hydrophobic portion forms a very stable alpha-helix. The hydrophilic N-terminal
      part adopts an alpha-helix configuration which is much less stable except for the
      stretch containing the phosphorylation sites.

PMID- 8554578
TI  - Lipoteichoic acid-induced neutrophil adhesion via E-selectin to human umbilical
      vein endothelial cells (HUVECs).
AB  - We investigated whether lipoteichoic acid (LTA) induces the expression of E
      selectin and neutrophil adhesion to human umbilical vein endothelial cells
      (HUVECs). LTA (0.01-30 micrograms/ml) induced the expression of E-selectin in a
      concentration-dependent manner with maximal response at 10 micrograms/ml. The
      expression level of E-selectin increased from 2 h after stimulation by LTA with
      the maximal level at 4-8 h. Neutrophil adhesion to LTA-treated HUVECs correlated
      with the levels of E-selectin expression. In addition, the adhesion was clearly
      inhibited by anti-human E-selectin monoclonal antibody CY-1787 as well as a
      sialyl Lewis X (SLeX) oligosaccharide. LTA-induced expression of E-selectin was
      inhibited by protein kinase C inhibitors, H-7 and staurosporine. These results
      indicate that LTA induced the expression of E-selectin and neutrophils adhered to
      HUVECs via E-selectin.

PMID- 8554579
TI  - Lipopolysaccharide induces manganese superoxide dismutase in the rat pancreas:
      its role in caerulein pancreatitis.
AB  - Intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 50
      micrograms/kg increased the activity and the mRNA level of manganese superoxide
      dismutase (Mn-SOD) but did not change those of copper/zinc-SOD (Cu/Zn-SOD) in the
      rat pancreas. Both the formation of pancreatic edema and the elevation of serum
      amylase during caerulein pancreatitis were significantly relieved in the rats
      pretreated with LPS (50 micrograms/kg) compared with the rats without the
      pretreatment. These results support the view that superoxides play a key role in
      the pathogenesis of caerulein pancreatitis, and that Mn-SOD in the pancreas may
      work as a defense against the development of this disease.

PMID- 8554580
TI  - Identification and localization of gene expression of a low M(r) GTP-binding
      protein, ram p25 in pituitary gland.
AB  - The localization of gene expression of a low M(r) GTP-binding protein, ram p25,
      was examined throughout the entire brain of adult rat by in situ hybridization.
      ram-mRNA was expressed predominantly in anterior and intermediate lobes of
      pituitary gland (hypophysis), and weakly in hippocampal formation. In other parts
      of brain, no significant expression of ram-mRNA was detected, indicating that ram
      p25 may have an important role(s) in adenohypophysis. In 15-day-fetal rat, the
      mRNA was observed to be expressed strongly in the primitive anterior lobe of
      pituitary gland. The ram p25 was also detected in bovine pituitary gland by a
      specific antibody and was purified to near homogeneity by stepwise column
      chromatographies. Biochemical characterization of the purified ram p25 revealed
      that the profile of [35S]GTP gamma S-binding activity was almost the same as that
      of recombinant ram p25 expressed in E. coli.

PMID- 8554581
TI  - Highly purified biotin synthase can transform dethiobiotin into biotin in the
      absence of any other protein, in the presence of photoreduced deazaflavin.
AB  - Biotin synthase from Bacillus sphaericus has been purified to homogeneity from a
      recombinant strain. The UV-visible spectrum of the pure protein reveals the
      presence of a [2Fe-2S] cluster. The enzyme is active in the conversion of
      dethiobiotin to biotin in vitro, in the presence of NADPH, AdoMet and additional
      unidentified components from the crude extract of B. sphaericus wild type. We
      have also found that photoreduced deazaflavin can substitute for the crude
      extract and NADPH. In this system, biotin synthase is capable of transforming
      dethiobiotin into biotin in the absence of any other protein but at a
      substoichiometric level. When this assay was conducted in the presence of
      [35S]cysteine, no 35S was incorporated into biotin, contrary to what happens in
      the presence of the crude extract.

PMID- 8554583
TI  - Streptokinase contains two independent plasminogen-binding sites.
AB  - Streptokinase (SK) exerts its thrombolytic effect by activating plasminogen (PG)
      indirectly, after the formation of an equimolar complex with either PG or plasmin
      (PN). The location and nature of the PG/PN-binding sites in SK have been explored
      using limited proteolysis with immobilized trypsin. Employing Western blotting
      with radiolabeled PG after SDS-PAGE of total tryptic digest, three fragments of
      MW 7 kD, 19 kD and 31 kD were found to possess PG-binding ability. Each of these
      fragments was then isolated by reverse phase HPLC and characterised with respect
      to its sequence, as well as its PG-binding properties by ELISA. These analyses
      revealed that in addition to a PG-binding site in the region 143-293 reported
      recently in the literature, there is another distinct, high-affinity and
      independent PG-binding site, located in the N-terminal region (residues 1-59) of
      SK. Using a synthetic peptide, the N-terminally located PG-binding-site has been
      further localised to the region 37-51 of SK. Further, we demonstrate that the PG
      binding of this peptide is not mediated through the lysine-binding sites
      ("Kringles") of PG. This stretch contains a short sequence (LTSRPA) that is also
      present in the PG-binding domain of human fibronectin.

PMID- 8554584
TI  - PI 3-kinase-dependent and independent chemotaxis of human neutrophil leukocytes.
AB  - The migration of neutrophil leukocytes to inflammatory sites is important for the
      elimination of microorganisms but can under pathological conditions lead to
      severe tissue damage. The initial chemotactic response is elicited by classical
      chemoattractants, such as fMet-Leu-Phe or the chemokine interleukin-8 which
      ligate to G-protein coupled receptors. Neutrophils show also a delayed
      chemotactic response to growth factors, such as platelet derived growth factor
      (PDGF) or tumor growth factor (TGF beta). We describe here that classical
      chemoattractants and growth factors stimulate neutrophil chemotaxis through
      different signal transduction pathways. Wortmannin, a selective
      phosphatidylinositol 3-kinase inhibitor, completely blocks growth factor
      stimulated chemotaxis while having no effect on neutrophil migration stimulated
      with classical chemoattractants. The results suggest that cell migration can be
      selectively controlled through the inhibition of distinct signal transduction
      events.

PMID- 8554582
TI  - Immunological and physical characterization of the brain G protein-gated
      muscarinic potassium channel.
AB  - The subunit composition of the G protein-gated inwardly rectifying K+ (KG)
      channel protein extracted from mouse forebrain membranes was examined. A
      polyclonal antibody (anti-GIRK1C1) was prepared against the carboxyl terminal
      region of GIRK1, the major subunit of the KG channel. The anti-GIRK1C1 IgG
      detected a single protein at approximately 65 kDa in SDS-PAGe of brain membranes.
      This IgG immunoprecipitated a macroprotein complex composed of GIRK1 and several
      associated proteins whose molecular weights ranging from 50 to 62 kDa on SDS
      polyacrylamide gel. Upon size fractionation by both sucrose density gradient
      centrifugation and gel filtration, the solubilized KG channel proteins migrated
      into a single peak, which suggests that the component subunits form a single
      macromolecule. On the basis of the values of size fractionation, the molecular
      mass of the KG channel macromolecule could be estimated at approximately 231,000.
      These results suggest that the KG channel is most likely a tetrameric
      macroprotein composed of GIRK1 and co-immunoprecipitated proteins in the
      forebrain.

PMID- 8554585
TI  - Phospholipase A2 is activated by tumor necrosis factor-alpha in primary
      hepatocytes stimulated by a deleted form of hepatocyte growth factor.
AB  - Several factors are released in the liver microenvironment immediately after
      injury. Among these factors TNF alpha is implicated as a regulator of hepatocyte
      proliferation. Hepatocytes in the intact liver are mostly in the G0 phase of the
      cell cycle and after injury (including collagenase perfusion) display a
      constitutive expression of the growth-regulated c-myc oncogene. TNF alpha co
      added with dHGF in hepatocyte cultures, superinduced the DNA synthetic response
      observed at all time points. In parallel, TNF alpha/dHGF-treated hepatocytes have
      shown increased expression of the c-myc oncogene at times corresponding to the in
      vitro G1 phase of the cell cycle. TNF alpha activated PLA2 in hepatocytes and it
      is believed that the subsequent production of PGE2 plays a role in the "priming"
      process in these cells and at the same time amplifies the proliferating signals
      induced by hepatocyte-specific growth factors.

PMID- 8554586
TI  - Selective regulation of steroid receptor expression in MCF-7 breast cancer cells
      by a novel member of the heregulin family.
AB  - A 52 kDa heregulin secreted by estrogen receptor (ER)-negative human breast
      cancer cells induced rapid growth of ER-positive MCF-7 breast cancer cells with a
      stimulatory effect observed at 10(-11)M. This heregulin down-regulated the
      message for ER in MCF-7 cells within 24 hours after stimulation. Similarly the ER
      protein was down-regulated within 24 to 48 hours after stimulation of cells.
      However, this down-regulation occurred without activation of the ER, since the
      progesterone receptor (PR) level of cells stimulated with the 52 kDa heregulin
      did not increase over the time period measured. As a control, estradiol down
      regulated and activated ER as shown by a pronounced increase in PR content of MCF
      7 cells. This finding indicates an important role of this heregulin in the down
      regulation of ER in estrogen-dependent human breast cancer cells.

PMID- 8554587
TI  - TGF-beta 1 overexpression in murine pancreas induces chronic pancreatitis and,
      together with TNF-alpha, triggers insulin-dependent diabetes.
AB  - We have generated transgenic mice overexpressing TGF-beta 1 in pancreatic beta
      cells. This resulted in massive fibrosis of the pancreas; in adult mice, most of
      the acini were replaced by fibrotic and adipose tissues. A conspicuous
      disorganization of the islets of Langerhans was also observed; however, the
      number of beta cells was not decreased and the mice were normoglycemic.
      Backcrossing to transgenic mice overexpressing TNF-alpha in their islet beta
      cells (which also remain normoglycemic, (1)) yielded double transgenics, most of
      which became diabetic by the age of 4 months; histological analysis revealed a
      dramatic decrease in insulin-containing beta cells.

PMID- 8554588
TI  - Functional characterization of the promoter region of the human phospholipid
      transfer protein gene.
AB  - We have identified the functional promoter region of the human phospholipid
      transfer protein gene. Primer extension analysis indicates multiple sites for
      transcription initiation. Sequence analysis reveals that the promoter consists of
      TATA box, high GC region, and several consensus sequences for the potential
      binding of transcription factors. To assay promoter activity, DNA fragments with
      various lengths of the 5'-flanking region were fused upstream to the luciferase
      gene and transfected into HepG2, COS-7, and CHO cells. A minimal promoter of 159
      base pairs between -230 and -72 relative to the first transcriptional initiation
      site is responsible for the full activity. Two motifs, Sp1 and AP-2, are located
      within this area. It may suggest that the PLTP promoter activity relies primarily
      on the putative cis-elements in the functional region.

PMID- 8554589
TI  - Human papillomavirus 11 E5a delays the growth restriction induced by temperature
      shift in temperature-sensitive simian virus 40 T antigen-immortalized
      keratinocytes.
AB  - The transfection with human papillomavirus type 11 E5a oncoprotein can cause
      longer and more active proliferation in the human keratinocytes previously
      transfected stably with temperature sensitive SV40 T antigen at 39 degrees C.
      Also, after the E5a transfection in parental temperature sensitive SV40 T antigen
      gene transfected cells, we observe a delay in the accumulation of p21 gene at 39
      degrees C. Moreover, T antigen degradation did not occur at 39 degrees C in the
      E5a transfected cells as it did in the parental cells. We draw from these
      observations that E5a may transiently stabilize temperature sensitive T antigen
      and/or repress p21 synthesis.

PMID- 8554590
TI  - Melanoma cell lines express VEGF receptor KDR and respond to exogenously added
      VEGF.
AB  - Tumour-secreted vascular endothelial growth factor (VEGF) exerts a number of
      effects which are important in tumour pathology, including stimulation of
      angiogenesis and permeabilisation of tumour-associated vasculature. In this study
      we have examined the possibility that VEGF may also play an autocrine role in
      tumour growth. Using reverse-transcriptase polymerase chain reaction (RT-PCR),
      the expression of VEGF was found in 15/15 human tumour cell lines examined, while
      the VEGF receptor KDR was detected only in three melanoma cell lines (MeWo and
      A375, both wild type and metastatic variant). Exogenously added VEGF (10ng/ml)
      was able to stimulate up to 40% increased proliferation of A375 M melanoma cells
      following a 48-h period of quiescence, suggesting that VEGF may indeed play a
      role in autocrine, as well as paracrine, stimulation of melanoma growth.

PMID- 8554591
TI  - Inhibitors of farnesyltransferase and Ras processing peptidase.
AB  - Four analogs of the carboxy terminus of unprocessed p21Ras protein were evaluated
      as inhibitors of the p21Ras processing farnesyltransferase and peptidase. While
      three showed no crossover of inhibitory activity between the enzymes, the fourth
      (a naphthyl-substituted peptide) inhibited both farnesyltransferase and
      peptidase, with IC50s of 16 microM and 3 microM, respectively. Such inhibition of
      more than one step of Ras processing may complicate assessment of the mode of
      action for some inhibitors of Ras processing peptidase.

PMID- 8554592
TI  - Biosynthesis of the so-called "a" and "asialo" pathway glycosphingolipids is
      differentially regulated in murine myelogenous leukemia NFS60 cells.
AB  - Regulation of "a" and "asialo" series ganglioside biosynthesis was analyzed. COS
      1 cells expressing only GD1a showed high synthetic activities of GM3, GM2, GM1a,
      and GD1a, but little activity for GA2 synthesis. However, IL-3-dependent murine
      NFS60-I7, which has GM1b and GD1 alpha, exhibited high synthetic activities of
      GM2, GM1a, and GD1a, but GM3 synthase was only 1/6 of COS-1 and GA2 synthetic
      activity was low. By contrast, IL-3 gene-transfected subline NFS60-H7 expressing
      GD1a in addition to GM1b and GD1 alpha displayed up-regulated GM3 synthase and
      GA2 synthase activities, while GM2, GM1a, and GD1a synthase activities were in
      the same levels as in NFS60-I7 cells. Since GA2 synthetic activities were not
      parallel with GM2 synthase in the investigated machinery of ganglioside
      biosynthesis, it is strongly suggested that biosynthesis of "a" and "asialo"
      series gangliosides is regulated differentially from each other in murine NFS60
      cell lines.

PMID- 8554593
TI  - Lipid peroxidation product, 4-hydroxynonenal and its conjugate with GSH are
      excellent substrates of bovine lens aldose reductase.
AB  - There is increasing evidence that lipid aldehydes generated endogenously during
      the process of degradation of lipid peroxides, are causally involved in the
      pathophysiology effects associated with oxidative stress. We report here that 4
      hydroxynonenal (HNE), which is one of the most abundant and toxic lipid aldehyde
      can be efficiently detoxified by the aldo-keto reductase, aldose reductase,
      purified from bovine lens. The enzyme displays a Km of congruent to 9 microM for
      HNE and 34 microM for the glutathione adduct of HNE (HNE-GS) assigning HNE and
      HNE-GS to be the best natural substrates of aldose reductase known so far and
      exposing a new efficient detoxification route of HNE.

PMID- 8554594
TI  - Differential phospholipid-labeling suggests two subtypes of phospholipase D in
      rat Leydig cells.
AB  - The aim of the present study was to compare the transphosphatidylation activity
      of phospholipase D (PLD) under different substrate labeling conditions, in order
      to investigate whether PLD in rat Leydig cells exhibited any substrate
      preferences for the alkyl- or acyl-form of phosphatidylcholine (PtdCho). The
      [3H]phosphatidylethanol formation in response to 4 beta-phorbol 12-myristate 13
      acetate (PMA), sphingosine, or Ca(++)-ionophore A23187, was lower when Leydig
      cells were labeled with 1-O-[3H]alkyl lysoPtdCho compared with the responses when
      [3H]myristic acid was employed. In contrast, the results for the receptor
      agonists (vasopressin, bradykinin, and lysophosphatidic acid), using the two
      labels, showed more consistency. Thus, the PLD-activity induced by PMA,
      sphingosine, or A23187 has a more selective substrate range (i.e. mainly acyl
      linked PtdCho) than the PLD-activity stimulated via a receptor. Our data suggests
      the existence of PLD isozymes that differ with respect to substrate specificity
      and activation mechanisms.

PMID- 8554595
TI  - The experimental hardness and electronegativity of the purines and pyrimidines in
      DNA and RNA supported by the AM1 calculation of the electron affinities and
      ionization potentials.
AB  - The ionization potential and electron affinities of the purines and pyrimidines
      in DNA and RNA were calculated with the AM1 semiempirical method. The values
      support the experimental values. The electron affinities are significant, and
      positive, such that donor-acceptor interactions can, and indeed should play a
      role in the stacking of bases in nucleic acids. Based on the confirmation of the
      experimental values by the theoretical calculations, reliable values of the
      experimental hardness and electronegativity were calculated.

PMID- 8554596
TI  - Endosomolytic activity of cationic liposomes enhances the delivery of human
      immunodeficiency virus-1 trans-activator protein (TAT) to mammalian cells.
AB  - We have explored the use of cationic liposomes to deliver the human
      immunodeficiency virus-1 trans-activator protein tat using a reporter gene
      expression assay. The human epidermoid carcinoma cell A431 stably transfected
      with a reporter gene under the control of human immunodeficiency virus-1 promoter
      was used as a target cell. Phosphatidylcholine-containing cationic liposomes had
      no detectable tat delivery activity. In contrast, delivery of tat was enhanced by
      up to 150-fold using cationic liposomes enriched with dioleoyl
      phosphatidylethanolamine (DOPE), a lipid which readily transforms a bilayer into
      a nonbilayer structure. Enhanced delivery of tat by DOPE-containing liposomes was
      most likely the result of the endosomolytic activity of the liposome. This
      phospholipid-rich formulation showed no toxicity at concentrations sufficient for
      maximal delivery of tat. A variety of cationic liposome formulations which
      contain DOPE were tested successfully for tat delivery.

PMID- 8554597
TI  - GM1492 human diploid skin fibroblasts lack the p53-dependent G1 cell-cycle
      checkpoint.
AB  - Recently, we reported that GM1492 human diploid skin fibroblasts derived from a
      Bloom's patient upon UV-C irradiation fail to increase p53 to a detectable level
      and nevertheless accumulate in the G1-phase of the cell-cycle. Here we show that
      in GM1492 cells other types of DNA-damaging agents also fail to induce p53 as
      well as WAF1, a p53-regulated gene product involved in G1 cell-cycle arrest.
      Furthermore, the p53-dependent G1 cell-cycle checkpoint is indeed defective in
      these cells: However, induction of GADD45 mRNA still occurs in GM1492 after
      irradiation with UV-C. Since GADD45 is known to inhibit the entry into S, these
      data suggest that the observed accumulation of GM1492 cells in G1 after UV-C
      irradiation occurs at the G1/S boundary and is due to an inhibition of initiation
      of DNA-replication.

PMID- 8554598
TI  - Purification of an alpha-2,8-sialyltransferase, a potential initiating enzyme for
      the biosynthesis of polysialic acid in human neuroblastoma cells.
AB  - alpha-2,8-Sialyltransferase has been purified from human neuroblastoma CHP-134
      cells greater than 2900-fold. The key step in the purification was a substrate
      affinity column utilizing immobilized colominic acid. Several kinetic parameters
      of the enzyme were defined. Fetuin but not asialofetuin served as substrate. The
      product of the enzyme reaction was characterized as containing sialyl residues in
      alpha-2,8-linkage with the use of recombinant sialidases. It is suggested that
      the purified enzyme is an initiating enzyme for the biosynthesis of polysialic
      acid since these cells also have the activity of poly alpha-2,8-sialyltransferase
      and contain polysialic acid. This alpha-2,8-sialyltransferase may be a new member
      of a family of alpha-2,8-sialyltransferases recently described, since it differs
      in substrate specificity reported for the cloned and expressed enzymes.

PMID- 8554599
TI  - E-selectin gene induction by ionizing radiation is independent of cytokine
      induction.
AB  - The mechanism of the x-ray-mediated inflammatory response in normal tissues is
      unknown. To determine whether leukocyte infiltration into irradiated tissue is
      regulated by adhesion molecule expression, we quantified the synthesis of
      glycoproteins that participate in inflammation. We found that E-selectin is
      synthesized in a time-dependent manner following exposure to doses as low as 0.5
      Gy. Northern blot analysis demonstrated that E-selectin mRNA expression increased
      at 2 h after x-irradiation and increased expression required no de novo protein
      synthesis. Transcription of the promoter region of E-selectin (-578 to +35) was
      transiently induced following x-irradiation, whereas deletion of the NFkB binding
      site eliminated x-ray induction. Electrophoretic mobility gel shift analysis
      confirmed increased binding of nuclear proteins from irradiated endothelial cells
      to the NFkB binding sequence from the E-selectin promoter. Nuclear protein
      binding to the NFkB binding sequence was altered by antibodies to the p50 and p65
      components of NFkB. These data demonstrate that E-selectin expression does not
      require cytokine synthesis, but involves NFkB activation.

PMID- 8554600
TI  - Increase in osmotolerance of Rhizobium fredii soybean isolate BD32 by the proB
      proA operon of Escherichia coli.
AB  - The proB proA operons (which are blocked by the feedback inhibition of proline
      production) of Escherichia coli wild type or with the mutation proBosm, blocking
      feedback inhibition effect of proline production, were cloned in a broad host
      range shuttle vector pVA 12-2. The hybrid plasmids pLVA(proB+A+) and pNSA(proBosm
      proA), were transferred into a low level osmotolerance Rhizobium fredii strain
      BD32. Both types of transconjugants were characterised by increased osmotolerance
      in a minimal medium supplied with 0.4-0.8 M NaCl but in the case of pNSA the
      effect was more significant. The strain BD32/pNSA had an increased level of
      intracellular proline concentration. Practical application of the increase in
      Rhizobium resistance to the stress factors is discussed.

PMID- 8554601
TI  - Characterization of the DNA-binding activity of HIV-1 integrase using a filter
      binding assay.
AB  - Based on the selective binding of proteins and DNA to distinct filter materials a
      double-layered dot blot radio assay was developed to evaluate the binding of DNA
      to HIV-1 integrase. In this assay the DNA-binding was found to be independent of
      Mn2+ concentration, inhibited by concentrations of Mg2+ above 5 mM, abolished by
      zinc chelation and inhibited by monoclonal antibodies reacting with either the N
      terminal or C-terminal regions of integrase. Atomic absorption spectroscopy
      revealed the molar ratio between integrase and zinc to be close to 1. It is
      concluded that both the N-terminal and the C-terminal regions of integrase are
      involved in DNA-binding and that the reported double-layered dot blot radio assay
      is well suited for further characterization of the integrase.

PMID- 8554602
TI  - Lysophosphatidylcholine inhibits NMDA-induced currents by a mechanism independent
      of phospholipase A2-mediated protein kinase C activation in hippocampal glial
      cells.
AB  - Lysophosphatidylcholine (LysoPC), which is formed by phospholipase A2 (PLA2)
      mediated phosphatidylcholine hydrolysis, is involved in enhancement of the
      diacylglycerol- or phorbol ester-dependent protein kinase C (PKC) activation. In
      the present study, the effect of lysoPC on NMDA-evoked currents was examined by
      whole-cell patches in cultured rat hippocampal glial cells. NMDA activated the
      receptor channel and produced currents in glial cells. LysoPC reversibly
      inhibited the NMDA-gated currents by 43% and this inhibition was not affected by
      a selective PKC inhibitor, GF109203X. These results indicate that lysoPC inhibits
      NMDA-induced currents by a mechanism independent of PLA2-mediated PKC activation.
      A possible explanation for the effect could be that lysoPC directly alters
      channel-gating kinetics of NMDA receptor or interacts with membrane components
      surrounding NMDA receptors.

PMID- 8554603
TI  - Bronchial epithelial cells of atopic patients with asthma lack the ability to
      inactivate allergens.
AB  - The cause of asthma is still unknown. Though most asthmatic patients are atopic,
      only certain atopic subjects develop this disease, and atopic asthmatics recover
      from asthma after transplantation of lungs from nonasthmatic donors. Thus, there
      might be a primary local defect in the bronchial wall which affects the
      expression of asthma in atopic individuals. We show here that the bronchial
      epithelial cells from atopic patients with asthma are aberrantly permeable to the
      airborne allergen most often implicated in the pathogenesis of this disease,
      indicating how it can have access to the antigen-presenting cells (dendritic
      cells) below the apical surface of the epithelium in vivo. In addition, allergen
      exposure induces asthmatic epithelial cells to express granulocyte/macrophage
      colony-stimulating factor, a cytokine involved in the proliferation and function
      of dendritic cells.

PMID- 8554604
TI  - The MDR1 downstream promoter contains sequence-specific binding sites for wild
      type p53.
AB  - We have examined the interaction of the wild-type p53 protein with the downstream
      promoter of the human multidrug resistance gene-1 (MDR1). Our findings indicate
      that wild-type p53 inhibits reporter activity driven by the MDR1 downstream
      promoter (base pairs -189 to +133 relative to the major transcriptional
      initiation site) in a dose-dependent manner in cotransfection assays in the BHK
      and the Saos-2 cell lines. A 123 base-pair segment of DNA (-119 to +4 relative to
      the major transcriptional initiation site), a 193 base-pair segment (-189 to +4),
      and a 135 base-pair segment (-2 to +133) have been isolated from the MDR1
      downstream promoter which, like the full promoter, are negatively controlled by
      wild-type p53. In addition, we show sequence-specific binding of wild-type p53
      protein to the MDR1 downstream promoter. These in vitro results suggest that the
      presence of wild-type p53 negatively affects expression of the MDR1 gene product,
      p-glycoprotein, at the transcriptional level.

PMID- 8554605
TI  - Identification of an orphan receptor gene as a type 1 calcitonin gene-related
      peptide receptor.
AB  - Calcitonin gene-related peptide (CGRP) is a 37 residue neuropeptide that is
      distantly related to adrenomedullin. We have recently reported the cloning and
      expression of an adrenomedullin receptor which is approximately 30% homologous to
      the canine orphan receptor RDC-1. Therefore we tested the hypothesis that RDC-1
      was a CGRP receptor. The RDC-1 gene was expressed in COS-7 cells and showed a
      dose dependant increase of cAMP in response to CGRP and adrenomedullin (EC50
      values of 3 x 10(-9) M and 1 x 10(-7) M respectively) which was inhibited by the
      CGRP antagonist CGRP[8-37]. There was no cAMP response to amylin or
      [Cys(acm)2,7]a-hCGRP. Ligand binding studies confirmed high affinity of this
      receptor for CGRP and CGRP[8-37] with KD values of 9.2 x 10(-9) M and 13.4 x 10(
      9) M respectively.

PMID- 8554606
TI  - Ubiquitin gene expression in skeletal muscle is increased during sepsis:
      involvement of TNF-alpha but not IL-1.
AB  - Septic rats showed an enhanced expression in skeletal muscle of both 1.2 (500%)
      and 2.4 (530%) kb mRNAs for the peptide ubiquitin, which reflects the activity of
      the ATP-ubiquitin-dependent proteolytic system. An acute intravenous
      administration of 100 micrograms/kg body weight of human recombinant tumour
      necrosis factor-alpha (TNF) also resulted in an important increase in the levels
      of ubiquitin mRNAs in rat skeletal muscle, while administration of a similar
      amount of human recombinant interleukin-1-beta did not. The results presented
      here, together with previous observations demonstrating that TNF increases the
      conjugation of proteins with ubiquitin in rat skeletal muscle (1), suggest that
      the ubiquitin system for non-lysosomal protein degradation could have a very
      important role in the mechanism triggered by TNF which is responsible for
      enhanced muscle proteolysis in sepsis and other pathological states.

PMID- 8554607
TI  - Isolation of AF2 (KHEYLRFamide) from Caenorhabditis elegans: evidence for the
      presence of more than one FMRFamide-related peptide-encoding gene.
AB  - Numerous FMRFamide-related peptides (FaRPs) have been isolated and sequenced from
      extracts of free-living and parasitic nematodes. The most abundant FaRP
      identified in ethanolic/methanolic extracts of the parasitic forms, Ascaris suum
      and Haemonchus contortus and from the free-living nematode, Panagrellus
      redivivus, was KHEYLRFamide (AF2). Analysis of the nucleotide sequences of cloned
      FaRP-precursor genes from C. elegans and, more recently, Caenorhabditis vulgaris
      identified a series of related FaRPs which did not include AF2. An acid-ethanol
      extract of Caenorhabditis elegans was screened radioimmunometrically for the
      presence of FaRPs using a C-terminally directed FaRP antiserum. Approximately 300
      pmols of the most abundant immunoreactive peptide was purified to homogeneity and
      30 pmols was subjected to Edman degradation analysis and gas-phase sequencing.
      The unequivocal primary structure of the heptapeptide, Lys-His-Glu-Tyr-Leu-Arg
      Phe-NH2 (AF2) was determined following a single gas-phase sequencing run. The
      molecular mass of the peptide was determined using a time-of-flight mass
      spectrometer and was found to be 920 (MH+)+, which was consistent with the
      theoretical mass of C-terminally amidated AF2. These results indicate that C.
      elegans possesses more than one FaRP gene.

PMID- 8554608
TI  - Glycolipid acceptor specificity of a human Gal beta(1-3/1-4) GlcNAc alpha 2,3
      sialyltransferase.
AB  - A human Gal beta(1-3/1-4)GlcNAc alpha 2,3-sialyltransferase, called ST-4, is a
      sialyltransferase involved in the in vivo biosynthesis of sialyl Lewis X (NeuNAc
      alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc) determinant. The ST-4 enzyme could
      utilize nLc4Cer (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1'Cer)
      containing type 2 sugar chain, Lc4Cer (Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc
      beta 1-1'Cer) containing type 1 sugar chain, Gg4Cer (Gal beta 1-3GalNAc beta 1
      3Gal beta 1-4Glc beta 1-1'Cer), and LacCer as glycolipid acceptor substrates, but
      not other neutral glycolipids (GalCer, GlcCer, Gb3Cer, Gg3Cer, Gb4Cer) and
      gangliosides (GM1a, GM2, GM3, GD1a, GD1b, and GT1b) as substrates. The order of
      sialic acid incorporation into glycolipids for the enzyme was nLc4Cer > Gg4Cer >
      Lc4Cer > LacCer. The apparent Km values of ST-4 for nLc4Cer and Gg4Cer were 0.47
      and 2.5 mM, respectively. Thus, the ST-4 could efficiently utilize both nLc4Cer
      and Gg4Cer as glycolipid acceptor substrates in vitro, suggesting that the
      substrate specificity of the enzyme may be similar to that of a glycolipid
      sialyltransferase (SAT-3), which is defined as the enzyme that uses both nLc4Cer
      and Gg4Cer as glycolipid acceptor substrates.

PMID- 8554609
TI  - Structures stabilizing the dimer interface on human 11 beta-hydroxysteroid
      dehydrogenase types 1 and 2 and human 15-hydroxyprostaglandin dehydrogenase and
      their homologs.
AB  - Human 11 beta-hydroxysteroid dehydrogenase-types 1 and 2 and human 15
      hydroxyprostaglandin dehydrogenase belong to a large family of oxidoreductases
      that includes human dihydropteridine reductase and Streptomyces hydrogenans 20
      beta-hydroxysteroid dehydrogenase, for which 3D structures are available. Almost
      all of these enzymes are either dimers or tetramers. The dimer interface of rat
      dihydropteridine reductase consists of alpha-helices E and F from each monomer
      arranged in a four alpha-helix bundle [Varughese et al. (1992) Proc. Natl. Acad.
      Sci. USA 89, 6080-6084]. Alpha-helix F contains tyrosine-146 and lysine-150,
      residues that are highly conserved in this protein superfamily and have been
      proposed to be at the catalytic site. We have examined the dimer interface
      between alpha-helix F in human and rat dihydropteridine reductase and
      Streptomyces hydrogenans 20 beta-hydroxysteroid dehydrogenase as well as modeled
      3D structures of steroid and prostaglandin dehydrogenases and homologs for
      stabilizing interactions. We find a site in the middle of alpha-helix F that
      stabilizes the dimer. This anchor is adjacent to conserved lysine on alpha-helix
      F. Our analysis suggests that sequence variation in the anchor may be important
      in substrate specificity.

PMID- 8554610
TI  - Multivalent binding of complement protein C1Q to the amyloid beta-peptide (A
      beta) promotes the nucleation phase of A beta aggregation.
AB  - Activation of the classical complement pathway has been proposed as a mechanism
      of neurodegeneration in Alzheimer's disease. This activation is a result of the
      binding of C1q to amyloid beta-peptide (A beta). Recent work has shown that A
      beta/C1q binding has an additional consequence: enhanced formation of the
      neurotoxic, fibrillar, cross beta-pleated A beta configuration. Here we show that
      C1q enhances A beta aggregation at physiologically relevant, nanomolar
      concentrations of the peptides, and demonstrate that the kinetics of this
      enhancement are consistent with a nucleating interaction. We also show that the
      intact, multimeric structure of C1q, which offers multiple A beta binding sites
      spaced at 2-3 nm intervals, is required.

PMID- 8554611
TI  - Molecular analysis of Ras activation by tyrosine phosphorylated Vav.
AB  - Vav has been shown to activate Ras (1-3) and is regulated by tyrosine
      phosphorylation (1) or binding of diglycerides (3) to the cysteine rich domain.
      In the present study employing different Ras activation assay techniques using
      [3H]GDP release or [32P]alpha GTP-binding from membrane-bound or soluble
      recombinant Ras, we demonstrate that Ras activity can be increased by tyrosine
      phosphorylated Vav upon cellular stimulation via the IL-2 receptor or the TCR/CD3
      complex. Increase of [32P]alpha GTP-binding to Ras catalyzed by phosphorylated
      Vav is similar to the activity of immunoprecipitated Sos. The activity of Vav
      measured by binding of [32P]alpha GTP to Ras was linear with respect to the
      concentration of Vav protein used. To study molecular characteristics of this Vav
      Ras interaction, we used several Ras mutants and demonstrate that Vav activity
      towards Ras depends on the integrity of the same or similar domains as Ras
      activation by SDC 25 or CDC 25.

PMID- 8554612
TI  - Effect of different solubilizing agents on the aggregation state and catalytic
      activity of two purified rabbit cytochrome P450 isozymes, CYP1A2 (LM4) and CYP2B4
      (LM2).
AB  - The effects of different ionic and nonionic detergents and lecithin/Na cholate
      mixtures on the aggregation state and catalytic activity of two major inducible
      rabbit cytochromes P450, CYP1A2 (LM4) and CYP2B4 (LM2), both of which are highly
      aggregated in solution, have been compared. Nonionic detergents Emulgen 913 and
      Lubrol PX as well as the mixture of lecithin-cholate demonstrate the ability to
      induce the dissociation of P450 isozymes only to dimers, accompanied by an
      increase in their catalytic activity, especially in lecithin proteoliposomes.

PMID- 8554614
TI  - Thioredoxin-linked peroxidase from human red blood cell: evidence for the
      existence of thioredoxin and thioredoxin reductase in human red blood cell.
AB  - A thiol-dependent antioxidant protein (HRPRP) was previously reported as a
      predominant antioxidant protein in human red blood cell (RBC). The analysis of
      amino acid sequence of HRPRP with those of human PRP-like gene products indicates
      that HRPRP is identical to brain PRP (HPRP). This protein act as a peroxidase
      linked to thioredoxin (Trx)/thioredoxin reductase (TR). Until now, there was no
      evidence for Trx/TR system in RBC. The existence of the Trx/TR system in RBC was
      immunologically determined. A 58-kDa protein showing TR activity was partially
      purified from human RBC and characterized. Our results reveal that HRPRP act as a
      new type of peroxidase supported by Trx/TR system in human RBC.

PMID- 8554613
TI  - Agents that elevate cAMP inhibit human neutrophil apoptosis.
AB  - Neutrophil apoptosis, determined after 20 h in culture using standard criteria
      and shedding of cell surface CD16 (Fc gamma RIII), is dramatically inhibited, in
      a concentration-dependent manner, by the cAMP analogs, dibutyryl-cAMP and 8-Br
      cAMP, and the adenylyl cyclase activator, forskolin. Furthermore, the stable
      receptor-directed PGD2 mimetic, ZK 118.182, and the PGE2 mimetic, 11-deoxy PGE1,
      similarly inhibited apoptosis. The DP-receptor antagonist BW A868C blocked the
      effect of ZK 118.182 and the protein kinase A inhibitor H-89 reversed the
      inhibition of apoptosis induced by dibutyryl-cAMP. These results clearly show
      that neutrophil apoptosis is markedly attenuated by cAMP elevating agents. This
      nucleotide second messenger may play a fundamental role in controlling neutrophil
      longevity and pharmacological regulation of cAMP levels or actions may influence
      neutrophil apoptosis in vivo.

PMID- 8554615
TI  - The mechanism of sphingosine enhancement of phorbol ester-mediated phospholipase
      D activation in lymphocytes.
AB  - Tumor-promoting phorbol esters stimulate the production of phosphatidylethanol
      (PEt) in bovine lymph node lymphocytes through the activation of Phospholipase D
      (PLD). Sphingosine enhanced the 12-O-tetradecanoylphorbol-13-acetate (TPA)
      mediated formation of PEt in lymphocytes, while it had no effect by itself.
      Interestingly, the incorporation of labeled arachidonic acid into phospholipids
      was increased by sphingosine. Examination of the effect of sphingosine along with
      TPA on the incorporation of [1-14C]labeled-arachidonic acid into individual
      phospholipids revealed that they enhanced significantly the specific activity of
      only PC and lyso-PC fractions. These observations indicate that sphingosine does
      not activate PLD directly as TPA does. It appears that sphingosine increases the
      specific radioactivity of the substrate pool for PLD which results in an apparent
      increase in PEt when both sphingosine and TPA are present.

PMID- 8554616
TI  - Cyclic AMP phosphodiesterases of human and rat islets of Langerhans:
      contributions of types III and IV to the modulation of insulin secretion.
AB  - This study evaluated the contribution of isozymes of cAMP phosphodiesterase (PDE)
      to total PDE activity in human and rat islets using type-selective inhibitors.
      The effects of selected PDE inhibitors on insulin secretion from human and rat
      islets were also measured in order to assess the contribution of the various PDE
      isozymes to the modulation of insulin secretion. The data suggest that PDE III is
      quantitatively the most important PDE isozyme present in islets, accounting for
      up to 70% of the total activity. Lower, but measurable, levels of PDE IV activity
      were present. Approximately 20% of islet PDE is not inhibitable by agents
      selective either for PDE III or IV. Selective inhibition of PDE III stimulated
      insulin secretion, but inhibition of PDE IV had no effect. The effects of type
      selective inhibitors on PDE activity and insulin secretion were similar in human
      and rat islets.

PMID- 8554617
TI  - Survival of F-reticulocytes in sickle cell disease.
AB  - Fetal hemoglobin, Hb F, is known to be an important factor for clinical course of
      sickle cell disease, as it suppresses polymerization of sickle hemoglobin. To
      investigate the effect of Hb F on the survival of sickle reticulocytes (young red
      cells) in circulation, Hb F levels in individual reticulocytes and mature
      erythrocytes were quantified via fluorescence image cytometry. We first examined
      unfractionated SS cells from 3 patients with different Hb F levels, and found
      that Hb F levels in reticulocyte populations were always lower than those in
      erythrocyte populations. This suggests that subsets of reticulocytes with lower
      Hb F levels are removed during maturation while those with higher Hb F levels
      tend to survive to become erythrocytes. The distribution of Hb F in reticulocytes
      was different among these patients and seems to strongly affect the survival of F
      reticulocytes. We also analyzed density-separated fractions, and found that Hb F
      levels in reticulocytes found in the densest fraction were lower than those in
      lighter fractions. This suggests that reticulocytes with lower Hb F levels are
      susceptible to quick dehydration within their maturation period (1-2 days) in
      circulation.

PMID- 8554618
TI  - Reducing PIP2 hydrolysis, Ins(1,4,5)P3 receptor availability, or calcium
      gradients inhibits progesterone-stimulated Xenopus oocyte maturation.
AB  - In this report, we investigated the possibility that a product of
      phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown, inositol 1,4,5
      trisphosphate (Ins(1,4,5)P3), and its downstream effector, Ca2+, is involved in
      oocyte maturation. Microinjection of monoclonal antibody specifically directed to
      PIP2 into oocytes prior to progesterone addition inhibited meiotic maturation. In
      addition, preventing or suppressing the progesterone-induced increase in [Ca2+]i
      and maintaining cytosolic free Ca2+ of oocyte at 0.1 or 0.3 microM by Br2-BAPTA
      buffered Ca2+ solutions, completely blocked maturation. However, raising
      cytosolic Ca2+ concentration of oocyte to 1.0 or 3.0 microM, the inhibitory Br2
      BAPTA effects on oocyte maturation was greatly diminished. Finally,
      microinjection of heparin, a potent antagonist of Ins(1,4,5)P3 receptor,
      inhibited progesterone-induced oocyte maturation in a manner that is linearly
      proportional to its cytoplasmic concentration. These results strongly support the
      hypothesis that PIP2 turnover as well as Ins(1,4,5)P3-induced Ca2+ release play
      crucial roles in regulating normal meiotic cell division in Xenopus oocyte.

PMID- 8554619
TI  - Sequence analysis of one major basic beta-crystallin (beta Bp) of amphibian
      lenses: evolutionary comparison and phylogenetic relatedness between beta- and
      gamma-crystallins.
AB  - beta Bp-Crystallin, a major basic beta-crystallin of vertebrate eye lens, is
      developmentally regulated during the process of amphibian metamorphosis. In order
      to facilitate the determination of the primary sequence of this ubiquitous
      crystallin present in all vertebrate species, cDNA mixture was synthesized from
      the poly(A)+ mRNA isolated from bullfrog eye lenses. A protocol of Rapid
      Amplification of cDNA Ends (RACE) was used to amplify cDNAs encoding beta Bp
      crystallin by polymerase chain reaction (PCR). PCR-amplified product
      corresponding to beta Bp-crystallin was then ligated into pGEM-T vector and then
      transformed into E. coli strain JM109. One complete full-length reading frame of
      615 base pairs, which covers a deduced protein sequence of 205 amino acids,
      including the universal initiating methionine, was revealed by automatic
      nucleotide sequencing with a fluorescence-based dideoxynucleotide chain
      termination method. It shows 83, 74, 78 and 80 percent sequence similarity to the
      homologous beta 2 crystallins of chicken, rat, bovine, and human species,
      respectively, revealing the close structural relationship among beta Bp
      crystallins even from remotely related species. In this study phylogenetic trees
      based on nucleotide and protein sequences of various beta- and gamma-crystallins
      from different vertebrate classes are constructed using a combination of distance
      matrix and approximate parsimony methods, which corroborate the previous
      supposition that beta- and gamma-crystallins form a superfamily with a common
      ancestry.

PMID- 8554620
TI  - Differences in stability of recombinant apoaequorin within subcellular
      compartments.
AB  - Recombinant acquorin is widely used as an intracellular Ca2+ indicator within
      live cells. Our data shows that recombinant apoacquorin was unstable within the
      cytosol, with a half life of approximately 20 minutes. Targeting of the protein
      to subcellular organelles resulted in an increase in stability which may be due
      to either stabilisation of the photoprotein structure or the absence of the
      relevant proteases within the organelles. When the apoprotein was reconstituted
      with the prosthetic group coelenterazine, there was a substantial increase in
      it's half life in the cytosol. We propose that this variable stability makes
      acquorin an ideal reporter of gene expression.

PMID- 8554621
TI  - Activity of the bifunctional protein 4a-hydroxy-tetrahydropterin dehydratase/DCoH
      during human fetal development: correlation with dihydropteridine reductase
      activity and tetrahydrobiopterin levels.
AB  - The dehydratase activity of the bifunctional protein, 4a-hydroxy-tetrahydropterin
      dehydratase/DCoH was measured in liver during early human fetal development to
      determine whether it appeared in concert with the other components of the
      phenylalanine hydroxylating system. Catalytic activity of the dehydratase is
      detectable as early as 6.7 weeks and increases linearly with time, reaching 31%
      of the adult value by 17.3 weeks of gestational age. Close correlation was found
      with the development of dihydropteridine reductase, which increased linearly to
      37% of the adult value at 17.3 weeks of gestation. From 8-18 weeks of gestation
      tetrahydrobiopterin in fetal liver was 0.86 microM (33% of adult value). The
      ratio of 7-biopterin to 6-biopterin was more than 8-fold higher in fetal than in
      adult liver during this time. The co-development of 4a-hydroxytetrahydropterin
      dehydratase with dihydropteridine reductase strongly supports a physiologically
      significant role for the dehydratase in tetrahydrobiopterin regeneration. In
      addition, the results have lead to a hypothesis for the transient nature of the
      hyperphenylalaninemia observed in a variant form of PKU in which levels of 7
      biopterin are elevated.

PMID- 8554622
TI  - Induction of rat hepatic cytochrome P450 enzymes by myristicin.
AB  - The effect of myristicin on the expression of liver cytochrome P450s and its mRNA
      levels was examined in rats. Treatment of rats with myristicin (i.p., 500
      mumol/kg) caused 2-20 fold increases in liver P450 1A1/2, 2B1/2, and 2E1 enzyme
      activities relative to controls. Immunoblot analysis using anti-rat liver P450
      1A, 2B, and 2E1 showed that the increases in each of P450 protein levels by
      myristicin were consistent with those in enzyme activity levels. When increased
      levels of P450 mRNA by myristicin were examined by Northern blot analysis, levels
      of mRNA of P450 1A1/2 and 2B1/2 also increased. However, the level of P4502E1
      mRNA did not increase. The total amount of spectrally detectable P450, also
      increased about 1.5-fold following treatment of myristicin. These results
      demonstrate that myristicin is an inducer of rat liver P450 1A1/2, 2B1/2, and
      2E1, and that the induction involves increases in mRNA levels except in the case
      of P4502E1.

PMID- 8554623
TI  - Chlorogenic acid as a natural scavenger for hypochlorous acid.
AB  - The effect of chlorogenic acid (CGA) on the killing of Escherichia coli by
      hypochlorous acid (HOCI) was examined. CGA prevented E. coli from bactericidal
      action of HOCI in a concentration-dependent manner. HOCI reacted rapidly with
      CGA. By comparison with the one- and two-electron oxidation products produced by
      peroxidase and phenolase reactions, respectively, the main product was identified
      as o-quinone of CGA via the formation of o-semiquinone of CGA as an intermediate
      The quinone form of CGA reacted further with HOCI to yield unstable product(s).

PMID- 8554624
TI  - Heterotetramer formation of prenylated Rab3A with two Rabphilin-3A molecules.
AB  - Rab3A small GTP-binding protein and its putative target protein, named Rabphilin
      3A, are implicated in neurotransmitter release. We have investigated here the
      function of the lipid modifications of Rab3A (Mr approximately 25,000) in its
      interaction with Rabphilin-3A (Mr approximately 80,000). Lipid-modified GTP-Rab3A
      dimerized and lipid-unmodified one monomerized. Lipid-modified GTP-Rab3A (Mr
      approximately 50,000) formed a heterotetramer (Mr approximately 210,000) with two
      Rabphilin-3A molecules, whereas lipid-unmodified GTP-Rab3A formed a heterodimer
      (Mr approximately 105,000) with one Rabphilin-3A molecule. These results indicate
      that two lipid-modified GTP-Rab3A molecules form a heterotetramer with two
      Rabphilin-3A molecules.

PMID- 8554625
TI  - Genomic DNA organization of human mitochondrial very-long-chain acyl-CoA
      dehydrogenase and mutation analysis.
AB  - Very-long-chain acyl-CoA dehydrogenase (VLCAD) is a major enzyme catalyzing long
      chain fatty acids in the first step of mitochondrial beta-oxidation system.
      Inborn error of this enzyme can cause sudden infant death syndrome and
      hypertrophic cardiomyopathy is present at a significantly high frequency. To
      investigate VLCAD deficiency at the genomic DNA level, we cloned the VLCAD gene
      and analyzed the structure. The gene is about 5.4 kb long and contains 20 exons.
      We performed mutation analysis in two patients, both having a 105 bp deletion
      encompassing bases 1078-1182 in cDNA. A point mutation (GT-->AT) at 5' splice
      site of intron 11 was identified in both patients. This mutation seems to cause
      skipping of exon 11 corresponding to the 105 bp deletion. This is the first
      documentation of aberrant splicing in the VLCAD gene.

PMID- 8554626
TI  - A new type soluble guanylyl cyclase, which contains a kinase-like domain: its
      structure and expression.
AB  - A new type soluble guanylyl cyclase, designated as ksGC (kinase-like domain
      containing soluble guanylyl cyclase), was identified from a kidney cDNA library.
      By Northern blot analysis, expression of this novel guanylyl cyclase mRNA was
      found in lung, kidney and skeletal muscle. Although ksGC is a soluble type
      guanylyl cyclase, it is not a member of soluble alpha or beta guanylyl cyclases.
      The ksGC contains in its N-terminal region a protein kinase-like domain, which is
      usually a characteristic feature only of particulate type guanylyl cyclases. This
      unique feature of ksGC suggests a novel pathway of cGMP synthesis.

PMID- 8554627
TI  - Effects of 50 Hz magnetic fields on C-myc transcript levels in nonsynchronized
      and synchronized human cells.
AB  - The effects of 50 Hz electromagnetic fields (EMFs) on the expression of the c-myc
      oncogene, known to be involved in normal cell proliferation and possibly also in
      tumor processes, were investigated in nonsynchronized human lymphoid cells
      immortalized by Epstein-Barr virus. Viral injury to such cells makes them a good
      model for exploring the possible cancer-promoting effects of 50 Hz magnetic
      fields. Parallel experiments were conducted on human HL60 leukemic cells. Cells
      were exposed to sinusoidal 50 Hz EMFs at 10 microT or 1 mT for 20 min, 1 h, 24 h,
      or 72 h. Exposure was performed either immediately after refeeding or 1.5 h after
      refeeding. C-myc transcript values were assessed by Northern blot analysis and
      normalized to those of the noninducible gene GaPDH. No statistically significant
      difference between the c-myc transcript levels of control and exposed cells was
      found in lymphoid or leukemic cells under our experimental conditions, either
      after short exposures of 20 min and 1 h or after longer exposures of 24 and 72 h.
      Other experiments were carried out with pseudosynchronized cells in an attempt to
      establish whether cells were especially sensitive to 50 Hz magnetic field
      exposure in any particular phase of the cell cycle. Accordingly, cells were
      pseudosynchronized in G0/G1 by serum deprivation and exposed for 20 min to a 50
      Hz magnetic field, at 10 microT for lymphoid cells and 1 mT for HL60 cells. No
      significant difference was observed between the c-myc transcript levels of
      control and exposed cells for either of the synchronized cell types. These
      results for synchronized cells correlated with those for nonsynchronized cells.

PMID- 8554628
TI  - Fetal loss in mice exposed to magnetic fields during early pregnancy.
AB  - The effects of low-frequency magnetic fields (MFs) on early pregnancy were
      studied in CBA/S mice. The magnetic field was a 20 kHz, 15 microT sawtooth.
      Pregnant females were divided into four groups, two control groups and two
      exposed groups. One group was exposed to MFs continuously from day 1
      postconception (pc) until day 5.5 pc, and the other group was exposed
      continuously until day 7 pc. All animals were sacrificed on day 19 pc, the day
      before partus, and their uterine contents were analyzed. No significant increase
      in the resorption (early fetal death) rate was found in the exposed animals
      compared to the sham controls. In the group exposed during days 1.0-5.5 pc, the
      body weight and length of the living fetuses were significantly decreased. Except
      on day 3 pc (progesterone) and day 13 pc (calcium) in the treated groups, there
      were no significant differences in progesterone and calcium levels in peripheral
      blood. Implantation occurred on the same day in MF-treated and control animals.

PMID- 8554629
TI  - Exposure to oscillating magnetic fields influences sensitivity to electrical
      stimuli. I. Experiments on pigeons.
AB  - The comparison of two measurements of the pigeon threshold for electrical
      stimuli, performed 2 h apart, reveals stress-induced analgesia as a result of
      stressful manipulations between the two tests. When pigeons are exposed to a
      weak, oscillating magnetic field between the two measurements, the analgesic
      response is inhibited and a hyperalgesic effect is recorded. The present findings
      are in agreement with previous studies showing that magnetic treatments may alter
      pigeons' emotional state and some of their behavioral patterns.

PMID- 8554630
TI  - Exposure to oscillating magnetic fields influences sensitivity to electrical
      stimuli. II. Experiments on humans.
AB  - To assess the effect of a magnetic treatment on pain perception, we compared the
      sensory threshold in 18 healthy volunteers. We determined the threshold by
      noninvasive electrical stimulation of the tooth pulp and skin before and after
      exposure to an altered magnetic field of low intensity and to a sham treatment.
      Five different parameters were recorded: the sensory and pain thresholds for the
      tooth and the sensory, pain, and tolerance thresholds for the skin. Two hours of
      exposure to a weak, oscillating magnetic fields induced a significant decrease in
      three parameters (dental sensory and cutaneous pain and tolerance thresholds),
      whereas the other two parameters showed a similar tendency. When the same
      subjects were exposed to a sham treatment, only marginal, nonsignificant
      variations in all parameters were observed. These results represent the first
      piece of evidence that weak alterations of the magnetic field may induce
      hyperalgesia in humans.

PMID- 8554631
TI  - Failure to produce taste-aversion learning in rats exposed to static electric
      fields and air ions.
AB  - Taste-aversion (TA) learning was measured to determine whether exposure to high
      voltage direct current (HVdc) static electric fields can produce TA learning in
      male Long Evans rats. Fifty-six rats were randomly distributed into four groups
      of 14 rats each. All rats were placed on a 20 min/day drinking schedule for 12
      consecutive days prior to receiving five conditioning trials. During the
      conditioning trials, access to 0.1% sodium saccharin-flavored water was given for
      20 min, followed 30 min later by one of four treatments. Two groups of 14 rats
      each were individually exposed to static electric fields and air ions, one group
      to +75 kV/m (+2 x 10(5) air ions/cm3) and the other group to -75 kV/m (-2 x 10(5)
      air ions/cm3). Two other groups of 14 rats each served as sham-exposed controls,
      with the following variation in one of the sham-exposed groups: This group was
      subdivided into two subsets of seven rats each, so that a positive control group
      could be included to validate the experimental design. The positive control group
      (n = 7) was injected with cyclophosphamide 25 mg/kg, i.p., 30 min after access to
      saccharin-flavored water on conditioning days, whereas the other subset of seven
      rats was similarly injected with an equivalent volume of saline. Access to
      saccharin-flavored water on conditioning days was followed by the treatments
      described above and was alternated daily with water "recovery" sessions in which
      the rats received access to water for 20 min in the home cage without further
      treatment. Following the last water-recovery session, a 20 min, two-bottle
      preference test (between water and saccharin-flavored water) was administered to
      each group. The positive control group did show TA learning, thus validating the
      experimental protocol. No saccharin-flavored water was consumed in the two-bottle
      preference test by the cyclophosphamide-injected, sham-exposed group compared to
      74% consumed by the saline-injected sham-exposed controls (P < .0001). Saccharin
      preference data for the static field-exposed groups showed no TA learning
      compared to data for sham-exposed controls. In summary, exposure to intense
      static electric fields and air ions did not produce TA learning as assessed by
      this particular design.

PMID- 8554632
TI  - Absence of radiofrequency heating from auditory implants during magnetic
      resonance imaging.
AB  - The possibility of tissue heating due to an auditory brainstem implant (ABI) or a
      modified cochlear implant (CI) during magnetic resonance imaging (MRI) of the
      head was tested on a full-sized human phantom using a realistic phantom head
      consisting of simulated skull, brain, and muscle. Dielectric properties of the
      brain, muscle, and bone materials were similar to those of human tissues at 64
      MHz. The body consisted of homogeneous phantom muscle enclosed in a human-shaped
      fiberglass shell. Thermographic and fiber-optic temperature measurements were
      conducted to reveal any heating. Thermograms of sagittal, frontal, and horizontal
      planes of the head with the ABI and CI electrodes were taken immediately before
      and after a 26 min MRI scan. The MRI sequence was set at 94 excitations and 25 ms
      echo time to induce maximum radiofrequency heating, as suggested by the General
      Electric Company. The difference of these two thermograms gives the heating
      results. In two uncut phantom heads. Teflon tubes were placed along the implanted
      ABI and CI, and temperature data were recorded via fiber-optic probes before,
      during, and after the MRI. Results showed no observable heating associated with
      the ABI and the modified CI during worst-case MRI of the head.

PMID- 8554633
TI  - Do ELF magnetic fields affect human reaction time?
AB  - Two double-blind studies were run in an attempt to confirm the finding that a 0.2
      Hz magnetic field affects simple reaction time (RT) in humans, whereas a 0.1 Hz
      field does not. In the first experiment, 12 volunteer subjects were exposed to a
      continuous 0.2 Hz, 0.1 Hz, or sham field in a fully counterbalanced, within
      subjects design. Subjects were run singly for one condition each day over 3
      consecutive days with a field strength of 1.1 mT and a daily exposure duration of
      5 min. Neither magnetic field had any effect on RT at any time during the
      exposure. One condition of a second study, using a new group of 24 volunteer
      subjects, also failed to find any field effects at 0.2 Hz. Additionally, the
      second study failed to show any effects when the frequency, flux density, and
      field orientation were set according to parametric resonance theory. It is
      suggested that, although ELF magnetic field effects on human behaviour may be
      elusive, future research can improve detection rates by paying greater attention
      to reducing error variance and increasing statistical power.

PMID- 8554634
TI  - Effect of magnetic fields on rodent monooxygenase enzymes.
AB  - The effects of 50 Hz, 1.2 mT magnetic fields (MFs) were tested on hepatic
      monooxygenase enzymes of basal and beta-naphthoflavone-phenobarbital-preinduced
      rats and mice. An inductive effect on cytochrome P-450 level and on some
      enzymatic cytochrome P-450-dependent activities was observed in basal mice after
      MF exposure. Enzymatic activities in preinduced mice and rats were reduced by
      MFs, the degree of reduction depending on the enzyme. A specific inhibitory
      effect was determined in some of the assayed activities and in the relative
      peculiar P-450 isoforms detected by Western blot analysis.

PMID- 8554635
TI  - Effects of 50 Hz magnetic fields on mouse spermatogenesis monitored by flow
      cytometric analysis.
AB  - Flow cytometry (FCM) was performed to monitor the cellular effects of extremely
      low-frequency magnetic field on mouse spermatogenesis. Groups of five male hybrid
      F1 mice aged 8-10 weeks were exposed to 50 Hz magnetic field. The strength of the
      magnetic field was 1.7 mT. Exposure times of 2 and 4 h were chosen. FCM
      measurements were performed 7, 14, 21, 28, 35, and 42 days after treatment. For
      each experimental point, a sham-treated group was used as a control. The possible
      effects were studied by analyzing the DNA content distribution of the different
      cell types involved in spermatogenesis and using the elongated spermatids as the
      reference population. The relative frequencies of the various testicular cell
      types were calculated using specific software. In groups exposed for 2 h, no
      effects were observed. In groups exposed for 4 h, a statistically significant (P
      < 0.001) decrease in elongated spermatids was observed at 28 days after
      treatment. This change suggests a possible cytotoxic and/or cytostatic effect on
      differentiating spermatogonia. However, further studies are being carried out to
      investigate the effects of longer exposure times.

PMID- 8554637
TI  - Comments on "Sleep-inducing effect of low energy emission therapy" by Reite et
      al.

PMID- 8554636
TI  - Do rats show a behavioral sensitivity to low-level magnetic fields?

PMID- 8554638
TI  - Do not change the numbers--clarify the message. The government review of the
      Sensible Drinking message: a Medical Council on Alcoholism view.
AB  - This is an edited version of the evidence from The Medical Council on Alcoholism
      (MCA) on 'Sensible Drinking', which is based on the collective views of the
      Education and Public Health Committee and of The MCA Regional Advisers in medical
      schools throughout the UK. The contributors are not only university teachers, but
      also clinicians and health service providers in touch with patients and the
      public. On one aspect there is total unanimity. On no account should the 21/14
      units per week figures for men and women, respectively, be changed: the evidence
      indicates that this could only lead to increased harm. There seems to be some
      scope for restatement of the significance of the benchmark such as that 'below
      21/14 units per week is a sensible level, and that, at twice this level, there is
      an appreciable increase in risk of harm which continues to increase as
      consumption rises'. Drink-free days are recommended, but the need to suggest an
      additional curb on intake on any given occasion is also emphasized, since heavy
      consumption of this sort is that which is particularly associated with
      behavioural and psychosocial problems, notably in the young. Driving is an
      obvious example where any drinking could be dangerous. A simple statement such as
      'avoid intoxication and do not exceed 6/4 units in a day, while maintaining the
      weekly guidelines as at present and bearing in mind the circumstances' is
      proposed.

PMID- 8554639
TI  - Do cage scores predict readiness to reduce alcohol consumption in medical in
      patients?
AB  - Four-hundred-and-twenty-three medical in-patients received the CAGE, brief
      Michigan Alcohol Screening Test (MAST) and Readiness to Change (RCQ)
      questionnaires. Those positive on the CAGE and MAST were more likely to be in
      contemplation and action phases of the RCQ, suggesting that simple questionnaires
      identify patients who not only have drinking problems but are ready to make
      changes to combat them.

PMID- 8554640
TI  - Alcohol and oesophageal varices.
AB  - Oesophageal varices are abnormally dilated veins that develop beneath the mucosa
      of the lower oesophagus and upper stomach and cause profound gastrointestinal
      haemorrhage associated with a high mortality. Varices develop in the presence of
      protal hypertension, which, in Europe and the USA, is most commonly due to
      alcoholic cirrhosis of the liver. Alcoholic cirrhosis develops in 10-20% of
      chronic ethanol abusers as a result of prolonged hepatocyte damage, leading to
      centrilobular inflammation and fibrosis. The net effect on the portal venous
      system is an elevation of resistance, and/or increase of inflow, producing portal
      hypertension, and the development of collateral channels in the form of varices.
      Such parenchymal liver disease also causes ascites, clotting deficiencies,
      secondary malnutrition and hepatic encephalopathy, all of which contribute to the
      high mortality associated with variceal haemorrhage. Variceal bleeding is more
      likely to occur when the varices are large, long and numerous, with surface red
      markings, and may be precipitated to respiratory tract infection, non-steroidal
      anti-inflammatory drugs, alcohol, or may occur spontaneously. Once identified by
      endoscopy, the aims of management are to control the haemorrhage, to prevent
      recurrent haemorrhage, and to treat the underlying cause of portal hypertension.
      Attention to nutrition and long-term rehabilitation are particularly important in
      those alcoholic cirrhotic patients who survive.

PMID- 8554641
TI  - Prognosis of alcoholic liver disease--100 years on and the need for international
      standards and guidelines.
AB  - Studies of alcoholic liver disease show a wide variation in survival time. This
      article reviews the relevant literature and draws attention to differences in the
      measurement of survival. Different starting points, different classifications of
      drinking behaviour and variations in the terminology used to describe the
      histological features of different stages of liver disease make it difficult to
      compare survival figures from various studies. Definitions of excess alcohol
      intake and of what constitutes 'abuse' are also vague. Variations in the way
      results are expressed may show apparent differences in outcome where none exist
      in reality. Variations in size of study populations and loss to follow-up are
      also discussed. It is suggested that resources should be devoted to prevention
      and early detection of liver disease and that international guidelines are
      necessary for the adoption of standard terminology, classification of drinking
      behaviours and alcohol use, methods of analysis and expression of results.

PMID- 8554642
TI  - Influence of CGS 8216 on some acute effects of ethanol.
AB  - The central pharmacological effects of ethanol are well known and resemble those
      of the benzodiazepines (BZD). In addition BZD may interact with ethanol,
      resulting in enhanced cerebral depression. Ro 15-4513, BZD inverse agonist,
      potentially antagonizes a lot of effects of ethanol but not all. In our study,
      another BZD inverse agonist, CGS 8216, reverses the hypnotic effect of ethanol
      and hypoactivity in mice and rats. CGS 8216 increased also ethanol's locomotor
      stimulation in mice. This supports the hypothesis that some effects of ethanol
      are mediated by the GABA-BZD-chloride channel receptor complex. Our behavioural
      experiments described in this report suggest that CGS 8216, like Ro 15-4513, may
      act on the alpha-6 subunit of this receptor complex.

PMID- 8554643
TI  - Time course and genetic variation in the regulation of calcium channel antagonist
      binding sites in rodent tissues during the induction of ethanol physical
      dependence and withdrawal.
AB  - Physical dependence was induced by ethanol inhalation in male Sprague-Dawley rats
      and, in parallel experiments, in two lines of mice (WSR and WSP) genetically
      selected for differential severity of ethanol withdrawal. In dependent rats
      [3H]nitrendipine binding sites were significantly increased in cerebral cortex,
      cardiac and smooth muscle (vas deferens). Cerebral cortical membranes were the
      first to show an increase, the Bmax for nitrendipine binding rising sharply after
      3-4 days of ethanol administration, whereas binding sites in the other tissues
      increased after 5-6 days. Nitrendipine binding affinity in all tissues was
      consistently reduced immediately preceding the rise in Bmax to a new steady
      state, but then returned to control values. Between 6 and 10 days of ethanol
      exposure there was no further increase in the Bmax for nitrendipine binding, and
      on removal of ethanol, the numbers of nitrendipine binding sites fell
      precipitously to control levels within 24 h of withdrawal. In the genetically
      selected mice, the up-regulation of nitrendipine binding sites in cardiac
      membranes was significantly greater in the WSP line. This correlates with
      severity of physical signs of withdrawal and parallels previous results obtained
      in brain. The results are consistent with an increase in the synthesis and
      membrane insertion of dihydropyridine sensitive calcium channel proteins in
      several tissues during the induction of ethanol dependence and suggest that in
      the brain this change may play a role in the ethanol withdrawal syndrome.

PMID- 8554644
TI  - Ethanol decreases basal cytosolic-free calcium concentration in cultured skeletal
      muscle cells.
AB  - We analysed the effect of ethanol on basal cytosolic-free calcium concentration
      ([Ca2+]i) in cultured rat myocytes. Ethanol caused a dose-dependent decrease of
      the resting [Ca2+]i. Removal of ethanol was followed by a transitory increase of
      [Ca2+]i above the basal level. In cells chronically exposed to ethanol, [Ca2+]i
      normalized to the previous level.

PMID- 8554645
TI  - Analysis of ethanol and acetaldehyde recovery from perchloric acid-treated blood.
AB  - Recovery of acetaldehyde (0-20 microM) or ethanol (0-50 mM) added to blood and
      subsequently treated with perchloric acid (PCA) was evaluated using head-space
      gas chromatography and compared with controls. Using blood from five dogs, < 100%
      of acetaldehyde and ethanol was recovered from PCA-treated samples. Mathematical
      models of putative binding mechanisms indicated acetaldehyde partitioned simply
      between supernatant and PCA-induced precipitate and occupied < 1% of acetaldehyde
      binding sites on precipitate; ethanol partitioned simply between supernatant and
      precipitate and occupied > 62% of ethanol binding sites. The mathematical model
      also indicated acetaldehyde binding is 2500-fold stronger than ethanol binding.
      These results indicate as much as 46.4% of acetaldehyde may be bound to PCA
      induced precipitate formed in whole blood. This loss of acetaldehyde is 3- to 4
      fold greater than acetaldehyde loss caused by evaporation from PCA-treated blood.

PMID- 8554646
TI  - Acute encephalopathy and polyneuropathy after disulfiram intoxication.
AB  - A chronic alcoholic who had ingested a very high dose of disulfiram (29 g over a
      1-week period) without simultaneous alcohol intake developed an acute
      encephalopathy and a severe flaccid tetraparesis that worsened over the course of
      several days, even after the intake of the drug had stopped. Recovery was both
      slow and incomplete. One year after intoxication, the patient still had distal
      weakness in the arms and legs, and hypesthesia in the hands and feet.

PMID- 8554647
TI  - Encouraging drinking at safe limits on single occasions: the potential
      contribution of protection motivation theory.
AB  - Protection Motivation Theory (PMT) is considered as a possible framework for
      understanding and moderating higher-risk drinking. To this end questionnaire data
      were collected from 196 participants about levels of their current drinking and,
      after they have been alerted to the dangers of excess drinking on single
      occasions, their cognitions relating to drinking and their intentions for future
      single occasion drinking. Comparisons of higher and lower risk drinkers among the
      sample provided support for the applicability of PMT, revealing differences in
      their cognitions and in their adaptive and maladaptive coping. A supplementary
      path analysis revealed that health beliefs and coping strategies associated with
      PMT, together with demographics, account for 42% of the variance in behavioural
      intentions. These results suggest that PMT could prove a valuable tool for those
      working in alcohol research and education. Implications for the design of
      effective interventions are discussed.

PMID- 8554648
TI  - Physical morbidity in patients admitted to a private hospital for detoxification
      from alcohol.
AB  - A survey of patients admitted to a private hospital for detoxification from
      alcohol found similar levels of physical morbidity and withdrawal complications
      to a group admitted to a National Health Service alcohol treatment unit. Although
      private patients tended to be older than National Health Service patients, the
      two groups were similar on a number of other variables. The implications for
      those involved in the management of patients who abuse alcohol are discussed.

PMID- 8554649
TI  - Influence of selenium supplementation in non-toxic doses on testis lipid peroxide
      and antioxidant levels in chronic alcohol-fed rats.
AB  - Prolonged consumption of alcohol leads to peroxidative damage in testicular
      tissues and gonadal dysfunction. Selenium (Se) deficiency also gives rise to
      testicular structural and functional disturbances similar to those caused by
      alcohol. We examined the possibility that Se supplementation might, at least
      partially, prevent the testicular disorders induced by alcohol. Rats were fed
      alcohol and alcohol with 3 p.p.m. Se in drinking water for 5 months. Ethanol
      administration decreased vitamin C and glutathione levels in testicular tissue,
      but caused no alterations in vitamin E and polyunsaturated fatty acid levels.
      However, lipid peroxide levels were increased by alcohol. Selenium
      supplementation diminished both the depletion of vitamin C and the production of
      lipid peroxides, but did not affect the depletion of glutathione induced by
      alcohol in testicular tissue. In addition, Se supplementation ameliorated the
      decrement of serum testosterone levels induced by alcohol.

PMID- 8554650
TI  - The medical profile of unidentified problem drinkers in general practice: test of
      an hypothesis.
AB  - In order to facilitate general practitioner (GP) detection of problem drinkers
      the Dutch College of General Practitioners developed a standard specifying the
      differences in medical profile between problem drinker and non-problem drinkers.
      The standard mentions 35 Reasons for Encounter (RFEs) and GP Evaluations (Es)
      that are thought to be specific for problem drinkers. The studies referred to in
      the standard base their conclusions about differences in medical profile upon a
      comparison of problem drinkers already identified by the GP with other patients.
      This study tests the hypothesis that the medical profile specified by the
      standard also applies to unidentified problem drinkers. All known problem
      drinkers in the practices of 16 GPs, as well as a one in 10 random sample of
      patients considered to be non-drinkers were admitted to the study at their first
      surgery visit during a 1-year period. Hidden problem drinkers were detected by
      means of a screening questionnaire, although the results were not conveyed to the
      GP until the study was completed. Over the 1-year study period the GPs then
      registered all RFEs and Es of the study population. RFE and E sum scores were
      then constructed based on the Alcohol Standard. The estimated population
      prevalence of problem drinking, corrected for the one in 10 sample fraction was
      7%. We found 6% problem drinkers (n = 78) in the category regarded by the GPs as
      non-problem drinkers (n = 1254). Differences in RFEs and Es between hidden
      problem drinkers and those regarded as non-problem drinkers were significant for
      irregular heartbeat and psychological problems. Sexual problems were significant
      at the RFE level, social problems at the E level. When identified problem
      drinkers are compared with non-problem drinkers more differences in the medical
      profile are found (four times both RFE and E; twice RFE and once E). We conclude
      that most of the published differences in the medical profile between problem
      drinkers and other GP patients are not found for unidentified problem drinkers.
      The observed differences between unidentified problem drinkers and non-problem
      drinkers are too small to be helpful to the GP to detect problem drinkers.

PMID- 8554651
TI  - The thyrotropin releasing hormone stimulation test in alcoholism.
AB  - The mechanism for a blunted thyroid stimulating hormone (TSH) response to
      thyrotropin releasing hormone (TRH) in alcoholics is not known. We performed a
      combined TRH and gonadoliberin stimulation test on three well-defined groups of
      nondepressed alcoholic men. Group A comprised patients with acute withdrawal
      symptoms (n = 28), group B patients abstinent for 5-8 weeks (n = 29) and group C
      patients who had been abstinent for > 2 years (n = 16). Twenty-two healthy male
      volunteers were used for comparison. A blunted TSH response to TRH (delta TSH < 5
      microU/l) occurred only in groups A (39%) and B (17%). In group A delta TSH
      showed a significant negative correlation with the severity of withdrawal
      symptoms and a significant positive correlation with serum magnesium levels. In
      group B, patients with a family history of alcoholism had significantly lower
      delta TSH levels than those without such a family history. Groups did not differ
      with respect to basal and delta prolactin, and TSH responses were not
      significantly associated with vitamin deficiency, cortisol levels or free thyroid
      hormone levels. We conclude that TRH stimulation test blunting appears to be
      related to factors operating in the withdrawal state and improves with continued
      abstinence. A possible role of genetic factors and serum magnesium needs to be
      further explored.

PMID- 8554653
TI  - Ethnic differences in the biological consequences of alcohol abuse: a comparison
      between south Asian and European males.
AB  - Twenty-two South Asian men and 32 European men who had abused alcohol for at
      least 1.5 years were studied at the time of admission for detoxification to an
      Alcohol and Drug Dependency unit. The self-confessed average alcohol consumption
      during the preceding 3 months was similar in the South Asians (mean 383 g/day)
      and Europeans (mean 435 g/day) but the total duration of alcohol abuse was
      significantly shorter in South Asians (geometric mean 7.4 years) than Europeans
      (geometric mean 13.1 years). The geometric mean values for the concentration of
      carbohydrate-deficient transferrin in the serum were similar in the two ethnic
      groups. However, the red cell distribution width, the percentages of HbA1a+b,
      HbA1c and total HbA1 in red cell lysates and the activities of gamma-glutamyl
      transpeptidase, aspartate aminotransferase and alanine aminotransferase in the
      serum were all significantly higher in the South Asians than Europeans. The data
      suggest that South Asian men who abuse alcohol may be more susceptible to alcohol
      related liver damage and acetaldehyde-mediated haemoglobin modification than
      European men who abuse alcohol to a similar extent for a considerably longer
      period.

PMID- 8554652
TI  - Out-patient alcohol detoxification--outcome after 2 months.
AB  - We assessed the outcome after 2 months of 28 alcohol-dependent subjects following
      out-patient detoxification using an uncontrolled follow-up study with data
      collected at the time of detoxification (T1) and after 2 months (T2). We also
      determined the cost of out-patient versus in-patient detoxification. The setting
      was a psychiatric emergency clinic at a South West London University Hospital.
      Self-reported alcohol consumption in the week before T1 and T2, score on the
      'Alcohol Problems Inventory' measuring alcohol-related relational, occupation,
      legal and medical problems in the 2 months prior to T1 and T2, mean corpuscular
      volume and gamma-glutamyl transferase at T1 and T2 were used as outcome measures.
      Eight subjects had a 'good' outcome (seven were abstinent and one only drank four
      units on one day). Nine subjects were 'improved' by either having their alcohol
      consumption, or halving their 'Alcohol Problems Inventory' score at T2. 'Good'
      and 'improved' outcome were confirmed by mean corpuscular volume and gamma
      glutamyl transferase results. Eleven subjects were 'not improved'. Engagement
      following detoxification with voluntary alcohol agencies was associated with a
      better outcome. In-patient detoxification is calculated to be six times more
      expensive than out-patient detoxification. Out-patient detoxification is a cost
      effective step in the treatment of alcohol-dependent patients.

PMID- 8554654
TI  - Alcohol consumption and visual contrast sensitivity.
AB  - Visual contrast sensitivity (VCS) was measured in 30 alcoholic patients and 52
      controls. The results showed a significant reduction in VCS for all the spatial
      frequencies. The mean reduction for all spatial frequencies was 2.49 dB below the
      level of the control group. Optimal sensitivity corresponded to a lower spatial
      frequency in patients than controls, i.e. 1 cycle/degree (c/d) versus 2 c/d.
      Curves for VCS were normal for five patients. Abnormalities in VCS were
      suggestive of optic nerve dysfunction for 15 patients (50%), which were probable
      in seven cases (23%) and possible in eight others (27%). For 10 subjects, the
      abnormalities were indicative of ametropia. Daily alcohol intake and daily
      tobacco consumption were not significantly different in the patients who
      displayed VCS abnormalities, reflecting alcohol-tobacco amblyopia, from those who
      did not. The presence of higher gamma-glutamyl transpeptidase and mean
      corpuscular volume levels in patients who had VCS abnormalities indicative of
      alcohol-tobacco amblyopia suggests that alcohol consumption is involved in the
      development of these abnormalities.

PMID- 8554655
TI  - Neurologic manifestations of pediatric systemic lupus erythematosus.
AB  - Central nervous system involvement is a common but rarely reviewed feature of
      pediatric systemic lupus erythematosus (SLE). We retrospectively reviewed the
      charts of 91 patients with pediatric SLE and using a standardized data
      abstraction form documented 40 patients with central nervous system (CNS-SLE)
      involvement. The mean age of onset of SLE was 13.3 years. In 19 patients the CNS
      manifestation was a presenting symptom, in 12 patients CNS involvement was
      present within the first year of diagnosis, and in 9 patients it took up to 7
      years for CNS disease to become evident. Nineteen children (48%) manifested
      neuropsychiatric SLE, which included depression, concentration or memory
      problems, and frank psychosis. Seizures were present in 8 patients (20%), 6 had
      cerebral ischemic events (15%), 1 had chorea (3%), 2 had papilledema (5%), and 2
      patients had a peripheral neuropathy (5%). Nine patients (22%) had severe
      headache consistent with lupus headache. Seven children had more than one CNS
      manifestation. In the investigation of CNS-SLE, computed tomography and/or
      magnetic resonance imaging scans were helpful in patients with focal ischemic
      lesions and venous sinus thrombosis. Electroencephalography was abnormal only in
      33% of patients with seizure disorders and rarely helpful in patients with
      diffuse neuropsychiatric symptoms. Single-photon emission computed tomography
      scans were abnormal in most patients with neuropsychiatric SLE, especially in
      those with frank psychosis. The lupus anticoagulant was present in the patient
      with chorea and was frequently present in patients with cerebral vascular events.
      Long-term outcome was good: only 1 child died of cerebral hemorrhagic infarction
      and 3 others had significant persistent CNS deficits. The majority of patients
      (90%) had excellent recovery from CNS-SLE.

PMID- 8554656
TI  - Neurologic characteristics of childhood lupus erythematosus.
AB  - Records of 108 patients with lupus erythematosus beginning in childhood (1953
      1990) were reviewed; 25 had recorded neurologic findings. This is the largest
      group of childhood lupus erythematosus patients with neurologic disease that has
      been reported. The average age of children at the time of diagnosis of lupus was
      154 months. There were 22 girls and 3 boys in the group. All patients met at
      least four of the 1982 American Rheumatism Association criteria for the
      classification of systemic lupus erythematosus. Average age at onset of
      neurologic difficulties was 168 months. In 4 patients, the neurologic symptoms
      preceded the diagnosis: 1 month (spastic diplegia), 1 month (bilateral weakness
      and spasticity), 24 months (chorea), and 26 months (chorea), respectively. Four
      patients had neurologic symptoms coincident with the diagnosis of lupus
      erythematosus. In those patients whose symptoms followed the diagnosis of lupus
      erythematosus, the average elapsed time until symptoms appeared was 33 months;
      the single lowest and highest outliers were discounted. Most frequent findings
      were headache (16/25) and behavioral aberrations (10/25). All behavioral
      manifestations were depression except in 1 patient. Other prevalent findings
      included hemichorea or chorea (7/25), cerebrovascular accident with hemiplegia or
      diplegia (7/25), seizures (5/25), visual loss (3/25), and cranial neuropathy
      (2/25). Vertigo and myelopathy occurred in 1 patient each. All patients were
      treated primarily with corticosteroids and azathioprine; in the presence of
      active disease, the drug dosages were increased with significant improvement in
      neurologic symptoms. Resolution usually occurred from days to months; most
      improved in a few days to a few weeks; 3-4 months was the longest period until
      symptoms subsided.

PMID- 8554657
TI  - Reduced N-acetylaspartate in the brain observed on in vivo proton magnetic
      resonance spectroscopy in patients with mental retardation.
AB  - Volume-selective proton magnetic resonance spectroscopy (1H-MRS) of the brain was
      performed with a 1.5T magnet in 28 patients with unclassified mental retardation
      (MR) and in 25 age-matched healthy children. Peaks of N-acetylaspartate (NAA),
      choline (Cho), and creatine (Cr), but not of lactate, were observed in both
      groups on 1H-MRS. In all our subjects of this age range, 1H-MRS revealed an
      increase with advancing age in the ratio of NAA/Cho (P = .0031), but no
      developmental change in the NAA/Cr and Cho/Cr ratios. The NAA/Cho ratio was lower
      in patients with MR than in controls (P = .0016). The NAA/Cr ratio tended to be
      lower in the MR group, and the Cho/Cr ratio did not differ between patients with
      MR and controls. These results suggest that in patients with MR, NAA decreases
      and a disorder and/or dysfunction of neurons in the brain exists.

PMID- 8554658
TI  - The role of frameless stereotactic techniques in the treatment of pediatric CNS
      lesions.
AB  - The surgical management of children with deep-seated lesions within the brain and
      skull base or with superficial lesions within functionally important regions of
      the brain is often challenging. In order to optimize the functional outcome of an
      affected child, it is essential not only to adequately treat the offending
      lesion, but also to minimize injury to the surrounding brain. In this study, we
      examined the applicability of a video-interactive frameless stereotactic system
      for intraoperative localization and treatment of a variety of pediatric central
      nervous system problems, including craniotomy for tumor (n = 14), vascular
      malformation (n = 3), or cortical resection for intractable epilepsy (n = 4);
      ventricular puncture for shunt insertion in a patient with slit ventricles (n =
      2); transoral odontoid resection (n = 1); cannulation of a brainstem syrinx (n =
      1); removal of a foreign body (n = 1); and posterior craniocervical decompression
      (n = 1). The efficacy of the system was judged on several criteria: (1) the
      accuracy of the targeting achieved; (2) whether the system facilitated treatment
      of the lesions of interest; and (3) whether neurologic function was preserved. In
      general, the accuracy of the system for target localization was within 2-4 mm
      when rigid head fixation was employed intraoperatively. In such cases, frameless
      stereotactic guidance was extremely helpful in providing rapid and reliable
      assistance with operative planning, which facilitated the treatment of a variety
      of lesions in critical areas of brain with minimal neurologic morbidity.
      Limitations of this technology and potential solutions to these shortcomings are
      discussed. We conclude that the application of frameless stereotaxis for
      intraoperative localization represents a major advance in the treatment of a
      variety of intracranial processes in children by providing a means for accurately
      directing the approach to and removal of a targeted lesion while minimizing
      injury to the surrounding brain.

PMID- 8554659
TI  - Do ictal, clinical, and electroencephalographic features predict outcome in West
      syndrome?
AB  - Ictal electroencephalographic/video recordings of 42 patients with West syndrome
      (WS) were reviewed to define the relation between ictal, clinical, and EEG
      features and etiology or prognosis. The duration and type of spasms, the number
      of spasms per cluster, and the interval between spasms did not correlate with the
      etiology or the short-term prognosis. However, eye deviation, asymmetric spasms,
      and partial seizures concomitant with spasms were observed only in symptomatic WS
      patients with poor outcome. In particular, all 8 patients with concurrent partial
      seizures had severe psychomotor retardation. The ictal EEG characteristics did
      not correlate with etiology and prognosis. There was no significant difference
      between the patients with persistence or reappearance of hypsarrhythmia and the
      patients without interspasm hypsarrhythmia.

PMID- 8554660
TI  - Neonatal posthemorrhagic hydrocephalus: neuropathologic and immunohistochemical
      studies.
AB  - A neuropathologic study was undertaken to examine associated brain damage in
      patients with fetal and neonatal posthemorrhagic hydrocephalus (PHH). In PHH the
      association of periventricular leukomalacia and pontosubicular necrosis was not
      increased, but that of cerebellar subarachnoid hemorrhage and olivo-cerebellar
      pathology was significantly increased. All patients with the olivocerebellar
      pathology exhibited associated cerebellar subarachnoid hemorrhage and loss of
      Purkinje cells. Ferritin-positive glia were increased in the molecular layer of
      most patients, and glial fibrillary acidic protein-positive glia and/or fibers
      were increased in the molecular layer, granular layer, and white matter in older
      infants. Neonates with PHH had more severe brain lesions than those with only
      intraventricular hemorrhage. At 2 weeks of age in PHH, the ventricular wall
      displayed hemosiderin deposits and nodular gliosis, with ependymal cell loss and
      subependymal rosette formation. These findings may be closely related to the
      underlying pathogenesis and neurologic sequelae of PHH.

PMID- 8554661
TI  - Unprovoked seizures and developmental disabilities: clinical characteristics of
      children referred to a child development center.
AB  - Few data are available on the risk of seizures in young children with
      developmental problems. A retrospective evaluation of 1,946 children 0-5 years of
      age referred to the Tel Aviv Child Development Center (CDC) between 1981 and 1990
      was performed. The study was undertaken to determine the cumulative risk of
      unprovoked seizures in children referred to a CDC and to assess the risk factors
      associated with seizures in these children. The center serves the Tel Aviv area
      for a variety of developmental disabilities. Cumulative risk of seizures and risk
      factors were assessed using Kaplan-Meier methodology. Unprovoked seizures
      occurred in 58 patients (3%), including 10 with a single seizure and 48 with two
      or more seizures. Risk factors for seizures included cerebral palsy (CP)
      (relative risk [RR] = 28.7), neonatal seizures (RR = 15.2), mental retardation
      (MR) (RR = 7.8), febrile seizures (RR = 7.7), autism (RR = 3.2), and prematurity
      (RR = 2.7). The cumulative risk of seizures by age 5 years in children with MR,
      CP, and MR plus CP was 8%, 47%, and 68%, respectively, compared with 1% in those
      without MR or CP. On multivariate analysis, CP, MR, prior febrile seizures, and
      prematurity were associated with an increased risk of seizures. The risk of
      experiencing unprovoked seizures by age 5 in children with developmental
      disabilities is 3%, which is fourfold greater than that of the general
      population. Much of this increased risk is limited to selected subgroups with
      major disabilities. However, if neither MR nor CP is present, the 1% risk of
      developing unprovoked seizures by age 5 in children with other developmental
      problems is not substantially different from that expected in the general
      population.

PMID- 8554662
TI  - Bilateral striatal necrosis with a novel point mutation in the mitochondrial
      ATPase 6 gene.
AB  - A 2.5-year-old boy with bilateral striatal lesions is reported. Using polymerase
      chain reaction-single-strand conformation polymorphism analysis and direct DNA
      sequencing, a novel point mutation (T to C) at nucleotide 8851 of the
      mitochondrial DNA (mtDNA) was identified. This mutation changes a highly
      conserved tryptophan to arginine in subunit 6 of the mtATPase gene. The mutation
      was nearly homoplasmic and maternally inherited. This is the first published
      report of a mutation in the mtDNA in bilateral striatal degeneration. It is
      possible that other cases of bilateral striatal degeneration have been caused by
      mutations in the mtATPase 6 gene or genes encoding other subunits of the
      mtATPase; and therefore the mtATPase genes should be examined in children with
      this condition.

PMID- 8554663
TI  - Orofaciodigital syndrome type I in a patient with severe CNS defects.
AB  - A female patient with orofaciodigital syndrome type I associated with pachygyria,
      heterotopic gray matter, interhemispheric cyst, agenesis of the corpus callosum,
      and a Dandy-Walker anomaly is reported. Because some of these defects have been
      described in patients with different types of orofaciodigital syndromes, we
      recommend caution when using neuroradiologic criteria to separate these
      syndromes. Given the severe spectrum of brain abnormalities displayed by our
      patient, and considering their similarity with the brain defects formerly
      described in other X-linked dominant conditions with male lethality localized to
      Xp22, the use of DNA probes from Xp22 is advised in identifying the gene(s)
      causing orofaciodigital syndrome type I.

PMID- 8554664
TI  - Cerebral calcinosis and learning disabilities in hypoparathyroidism: a cause and
      effect or a coincidence?
AB  - A 12-year-old child is described in whom the presentation of learning
      difficulties and history of previous cataract removal led to a diagnosis of
      primary hypoparathyroidism. Cranial computed tomography revealed extensive
      calcinosis, previously described only in adults with long-standing
      hypoparathyroidism, and neuropsychologic evaluation revealed a marked symmetrical
      decrease in intellectual function. The possibility of the severe complication of
      brain calcinosis necessitates prompt diagnosis and treatment of
      hypoparathyroidism.

PMID- 8554665
TI  - Neuroleptic malignant syndrome in striatonigral degeneration.
AB  - A 6-year-old boy with striatonigral degeneration had an episode of neuroleptic
      malignant syndrome after an upper respiratory infection. Dantrolene treatment was
      successful. Some reports have demonstrated that anesthetic and antipsychotic
      agents lead to neuroleptic malignant syndrome in disorders of the basal ganglia.
      However, neuroleptic malignant syndrome attributable to a respiratory infection
      has not previously been reported. Our patient illustrates the potential morbidity
      of neuroleptic malignant syndrome in patients with striatonigral degeneration.

PMID- 8554666
TI  - Hydrocephalus, mineralizing angiopathy, hypercholesterolemia, and
      hyperlipoprotein (a).
AB  - A boy born at 34 weeks gestation with initially normal development presented with
      acute hydrocephalus at 22 months. Subsequently his development has been slow and
      complicated clinically by epilepsy. Upon extensive investigation, he has been
      found to have extremely elevated lipoprotein(a) levels, hypercholesterolemia
      (familial), and lesions of the cortex and meninges. Radiologic studies have
      disclosed a mineralizing angiopathy.

PMID- 8554667
TI  - Congenital ocular motor apraxia in two siblings.
AB  - Two siblings whose features met Cogan's classic description of congenital ocular
      motor apraxia were examined. There was first-degree consanguinity in the family.
      Each had an absence of voluntary and optically-induced horizontal eye movements
      and demonstrated classic head thrusting.

PMID- 8554668
TI  - Hopkins syndrome: T2-weighted high intensity of anterior horn on spinal MR
      imaging.
AB  - Hopkins syndrome is a poliomyelitis-like illness manifesting flaccid paralysis of
      an extremity in the recovery stage after an asthmatic attack. A 7-year-old boy
      who developed acute flaccid paralysis of the left upper extremity 4 days after an
      asthmatic attack is reported. T2-weighted magnetic resonance imaging of the
      cervical spine revealed a local high-intensity area in the left anterior horn at
      the C4 to C6 level. There have been few pathologic or radiologic studies of this
      syndrome. We suspect that the cause is an anterior horn lesion.

PMID- 8554669
TI  - Isolated sleep apnea due to Chiari type I malformation and syringomyelia.
AB  - We report an 11-year-old girl with Chiari type I malformation and syringomyelia,
      who experienced isolated sleep apnea without other neurologic problems.
      Monitoring with oximetry and movement of thoracic and abdominal walls indicated
      mixed-type sleep apnea. Chiari type I malformation should be differentiated from
      other disorders causing sleep apnea.

PMID- 8554670
TI  - Treatment of painful crises of Fabry disease with morphine.

PMID- 8554671
TI  - Three-dimensional structure of CA1 pyramidal cells in rat hippocampus--optical
      recording of LSM and computer simulation of fractal structure.
AB  - The optical recording of three-dimensional (3-D) reconstruction of CA1 pyramidal
      cells was derived from the studies on the CA1 region of the hippocampus in adult
      male Wistar rats. The recording was produced by the Confocal Laser Scan
      Microscope (LSM-10). The attemption was to outline the morphological neural
      network of CA1 pyramidal cells organization, following the trail of axo-dendritic
      connections in 3-D spatial distributions among neurons. The fractal structure of
      neurons with their dendritic and axonal trees using fractal algorithm was
      noticed, and 2-18 simulated cells were obtained using PC-486 computer. The
      simulational cells are similar in morphology to the natural CA1 hippocampal
      pyramidal cells. Therefore, the exploitation of an advanced neurohistological
      research technique combining optical recording of the LSM-10 and computer
      simulation of fractal structure can provide the quantitative fractal structural
      basis for chaosic dynamics of brain.

PMID- 8554672
TI  - Expression of human interleukin-11 cDNA in E. coli.
AB  - A 551-bp hIL-11 gene fragment that includes no nucleotide sequences encoding
      signal polypeptide and the initial 8 amino acids of the mature protein was cloned
      into a high-level expression vector pEx31B of E. coli. The authors identified the
      recombinant plasmid, designated pEx31-IL11, by restriction endonucleases
      digestion and DNA sequencing. The resulting recombinant plasmids were then used
      to transform E. coli strain HB101, and expression in the PL promoter system,
      which is temperature-regulated, was achieved. The expressed fusion protein
      amounts to 50% of total bacterial proteins. The hIL-11 protein expressed in E.
      coli was fused to the N-terminal 99 amino acids of the MS2 polymerase to form the
      inclusion body. These recombinant proteins can be purified to about 80% by
      extracting inclusion body with urea. One IL-6-dependent cell line 7 TD1 was used
      for bioassay. The recombinant hIL-11 protein was preliminarily purified and
      renatured to a specific activity of 10(5)U/mg, even in the presence of an excess
      of a neutralizing anti-IL-6 antibody.

PMID- 8554673
TI  - Cloning, expression and characterization of a single-chain antibody PS-9 targeted
      to pancreatic cancer.
AB  - Genes encoding single-chain antibodies have been first constructed, which consist
      of the heavy and light chain variable domains of antibody PS-9 joined together by
      a flexible peptide linker. The genes were cloned into coat protein g3p genes of
      pCANTAB5 phagemids, and expressed as fusion proteins on the phage tips.
      Immunological assay demonstrated that the engineered antibodies specifically
      bound to cancer cells LS-174-T as well as to pure bovine submaxillary gland
      mucin. Their specificity and affinity appeared the same as their parent
      antibodies. Our results supposed that the single-chain antibodies will be a
      target for the diagnosis and treatment of cancer.

PMID- 8554674
TI  - Developmental activity variations of DNA polymerase alpha, delta, epsilon in
      mouse forebrains and spleens.
AB  - The levels of DNA polymerase alpha, delta, epsilon were examined in the neonatal
      mouse forebrains and spleens. The levels of DNA polymerase alpha were determined
      by the difference of polymerase activity in the absence and the presence of alpha
      specific inhibitor, BuPdGTP, or its monoclonal antibody. The levels of DNA
      polymerase delta were determined in H.A fractions after separating it from the
      other two enzymes. The levels of DNA polymerase epsilon were identified in H.A
      fractions by the use of alpha-monoclonal antibody or BuPdGTP. Results showed that
      in the mouse forebrain DNA polymerase alpha, delta, epsilon activities are the
      highest before birth, decline sharply following birth and are very low on the 8th
      day and hardly detectable on the 17th day; as for the mouse spleen, however, DNA
      polymerase alpha, delta, epsilon activities are the lowest at birth, increase
      rapidly after birth and reach their maxima on the 8th day and then decline
      gradually but remain in higher levels. These results not only prove that DNA
      polymerase alpha and delta take part in cell DNA replication but also suggest
      that DNA polymerase epsilon is involved in DNA replication.

PMID- 8554675
TI  - Inhibitory effect of 3'-untranslated region (3'-UTR) of human tissue-plasminogen
      activator (ht-PA) mRNA on its expression.
AB  - A series of t-PA cDNA mutants containing different parts of 3'-UTR sequences have
      been constructed. In vitro translation of t-PA transcripts in rabbit reticulocyte
      lysates and its expression in COS-7 cells show that the 3'-UTR sequence has a
      very strong inhibitory effect on t-PA translation. The deletion of 3'-UTR results
      in 3-8-fold increase of t-PA expression. Further study shows that an AU-rich
      sequence of some 200 nt at 3' end of 3'-UTR is responsible for the translational
      inhibition. RNA stability experiment reveals that the AU-rich segment leads to a
      3-fold decrease of t-PA mRNA stability. The insertion of this segment into the 3'
      UTR of luciferase gene results in an obvious inhibition of Luc expression. A
      model is proposed for the regulation of t-PA expression.

PMID- 8554676
TI  - Biological activity assays of cell-free reassembled nuclei--injecting cell-free
      reassembled nuclei into unfertilized eggs can induce the eggs to cleave and
      reconstitute asters, and the injected nuclei undergo cell cycle changes.
AB  - Nucleus may reassemble spontaneously in cell-free mixture of HeLa metaphase
      chromosomes, Xenopus egg extracts and ATP-regenerating system, and the nucleus
      shows some biological activities. It is found that, after being injected into
      unfertilized mature eggs, the cell-free reassembled nuclei can cause the eggs to
      cleave and reconstitute asters in their cytoplasm, and the injected nuclei
      undergo changes in response to cell cycle regulators stored in the eggs, and that
      reinjecting cytostatic factors (CSF) into the eggs can stabilize the eggs in
      mitotic phase, cause the nuclei disassembly and chromatin condensation to
      chromosomes.

PMID- 8554677
TI  - High expression of synthetic human interferon-gamma cDNA in E. coli.
AB  - Human interferon-gamma (IFN-gamma) cDNA was synthesized, and it makes the usage
      of favorable codons in E. coli. The authors got 9 different expression plasmids
      which contain the synthetic IFN-gamma-cDNA and have different spaces between SD
      sequence and ATG. The free energies G0f298 in the formation of stable secondary
      structure in the translation initiation region (TIR) are different in various
      expression plasmids. One of them, pLY4-gamma 5, can highly yield INF-gamma which
      will be about 60%-80% of the total bacterial proteins, such a high expression was
      hardly noted in literature. The reasons of high expression in this work are
      optimal spaces between SD and ATC, favorable delta G0f298, favourable condons
      usage for E. coli.

PMID- 8554678
TI  - The crystal structure of deshexapeptide (B25-B30) insulin at 0.25 nm resolution.
AB  - The determination of deshexapeptide (B25-B30) insulin (DHI) was divided into two
      steps. At the first step, the rough structure model of DHI molecule was
      determined by using the molecular replacement method associated with the
      molecular close-packing method at 0.30 nm resolution based on the reflection data
      collected on four-cycle diffractometer. At the second step, the DHI model was
      adjusted and refined at 0.25 nm resolution based on the data collected on Area
      Detector. 40 water molecules were determined during the refinement, the final R
      factor is 0.185 with R.M.S. deviation of 0.002 nm for bond lengths and 1.9
      degrees for bond angles. The differences in conformation and function of DHI with
      other insulin analogues were compared and discussed.

PMID- 8554679
TI  - ESR study on calcineurin.
AB  - X-band electron spin resonance spectroscopy was used to investigate the binding
      of Mn2+ to the apo-forms of calcineurin and its A and B subunits. The results
      indicated the presence of 2 Mn2+ binding sites of different affinities (20
      mumol/L and 60 mumol/L) in the calcineurin A subunit and 4 Mn2+ binding sites in
      the calcineurin subunit B, 2 high affinity and 2 low affinity binding sites with
      Kd's of 4 mumol/L and 90 mumol/L, respectively. Interestingly and quite
      surprisingly, Mn2+ binding to the holoenzyme was characterized by only 2 binding
      sites with Kd's of 7 mumol/L and 33 mumol/L. However, in the presence of
      calmodulin about 10 Mn2+ sites were detected, and the Mn2+ calmodulin-calcineurin
      complex exhibited enzymatic activity. These results, based on direct spectral
      measurements of the metal ligand, demostrate that Mn2+ binds to both free
      subunits of calcineurin in a manner distinct from binding to the holoenzyme.
      Also, the data suggest that conformational changes occur upon heterodimer
      formation and association of the holoenzyme with the regulatory protein
      calmodulin.

PMID- 8554680
TI  - Some aspects of burns and burns research at Birmingham Accident Hospital 1944-93:
      A.B. Wallace Memorial Lecture, 1994.

PMID- 8554681
TI  - Functional and occupational outcome in patients surviving massive burns.
AB  - This report gives the results of follow-up observations on patients with massive
      burns covering > or = 50 percent TBSA (total body surface area) who survived for
      more than 2 years. The relationship between the functional and occupational
      recovery, and a discussion of the factors that may influence the functional
      rehabilitation and return to occupation or productivity, are presented.

PMID- 8554682
TI  - Plasma concentrations of type II phospholipase A2, cytokines and eicosanoids in
      patients with burns.
AB  - The plasma concentrations of type II phospholipase A2 (type II PLA2) and
      eicosanoids, such as leukotriene B4 (LTB4), 6-keto-prostaglandin F1 alpha (6-keto
      PGF1 alpha), and thromboxane B2 (TXB2), were determined by radioimmunoassay in 23
      patients with burns covering at least 20 per cent of their body surface.
      Cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6)
      and interleukin 8 (IL-8) were determined by enzyme-immunosorbent assay. There was
      no increase in type II PLA2 concentration in the early stage of burns, but an
      increase in type II PLA2 concentration was triggered by infection (P < 0.0001).
      The level of type II PLA2 was significantly higher in the non-surviving group
      than in the surviving group (P = 0.0006), suggesting that it reflects the
      severity of the disease. There was a significant correlation between the maximum
      level of type II PLA2 and TNF-alpha (r = 0.6346, P = 0.0011). There was a
      significant correlation between the maximum level of type II PLA2 and the
      accompanying plasma concentrations of LTB4, 6-keto-PGF1 alpha, and TXB2
      throughout the observation period (r = 0.4814, P = 0.0200; r = 0.5943, P =
      0.0028; r = 0.4368, P = 0.0372 respectively). Plasma levels of LTB4, and TXB2
      were significantly higher in the burn patients who died than in those who
      survived (P = 0.0493; P = 0.0493 respectively).

PMID- 8554683
TI  - Expression of the adhesion molecule CD11b and polymerization of actin by
      polymorphonuclear granulocytes of patients endangered by sepsis.
AB  - The integrin CD11b is an important adhesion molecule mediating the
      transendothelial migration of circulating polymorphonuclear granulocytes into an
      inflammatory region. The expression of CD11b is closely related to the ability to
      polymerize actin, a major component of the cytoskeleton within the phagocyte. In
      this study we compared the CD11b expression as well as the polymerization of
      actin of isolated neutrophils from patients endangered by sepsis with cells from
      healthy donors. The patient population was subdivided into a group of patients
      with severe thermal injuries and a group of patients who were admitted to an
      intensive care unit on suspicion of sepsis. The following results were obtained:
      (1) cells from burn patients, but not from non-burn patients, showed a reduced
      basal expression of CD11b during the first week after the burn trauma; (2)
      stimulation with the chemotactic peptide formyl-Met-Leu-Phe (FMLP) led to a
      strong overexpression of CD11b on the cells from the burn patients, this effect
      was not observed using cells of the second subgroup; (3) the content of
      polymerized actin was reduced within resting and stimulated cells from burn
      patients during the first 2 weeks postinjury, non-burn patient cells showed an
      enhanced F-actin content within the first week; (4) the ability of burn and non
      burn patient cells to polymerize actin after stimulation with FMLP was slightly
      impaired during the first week post injury/admission. The results demonstrate
      that cells from patients endangered by sepsis show dysfunctions on the level of
      adhesion molecule expression and the strongly related actin
      polymerization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554684
TI  - Analysis of changes in coagulation factors after postoperative blood loss in burn
      and non-burn patients.
AB  - A prospective study of the postoperative kinetics of coagulation factors was
      undertaken in 23 burn patients and in six non-burn patients. All procedures
      resulted in a large volume blood loss. Fibrinogen, platelets and factors V, VIII
      and IX were measured serially. Burn patients returned all parameters to
      preoperative levels by 48 h postoperation, while non-burn patients showed a
      slower rate of return of platelets and factor V. This study suggests that burn
      patients may safely undergo re-operation at 48 h intervals for successive wound
      debridements if clinically necessary.

PMID- 8554685
TI  - Serum cytokine levels (IL-4, IL-6, IL-8, G-CSF, GM-CSF) in burned patients.
AB  - The presence and concentration of selected cytokines (interleukin 4 (IL-4),
      interleukin 6 (IL-6), interleukin 8 (IL-8), granulocyte colony-stimulating factor
      (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were
      evaluated in the sera of 12 burned patients (6-90 per cent body surface area).
      The presence of cytokines in the sera of 20 healthy volunteers (control group)
      was always undetectable (< 2 pg/ml). In sera of the burned patients the
      concentrations of IL-4 or GM-CSF were also below the test sensitivity levels,
      while G-CSF and IL-6 were present throughout all the observation period and IL-8
      was detectable at the onset of massive infections. The serum concentrations of G
      CSF and IL-6 increased during the episodes of clinically and bacteriologically
      detectable infections. Their increases were, however, observable 12-24 h later
      than the other infection symptoms. Similar increases in G-CSF and IL-6 levels
      have been detected during corrective surgery (covering of granulation tissue with
      skin grafts). It may be concluded that serum G-CSF and IL-6 levels in burned
      patients may be considered as diagnostic factors, but the delays in the reaction
      to the massive infection do not allow us to use them for predicting the time of
      onset of the infection.

PMID- 8554686
TI  - Studies on multiple Pseudomonas aeruginosa isolates from individual burn patients
      by RFLP, O antigen serotyping and antibiogram analysis.
AB  - Multiple isolates of Pseud. aeruginosa from individual burn patients were tested
      for antibiotic susceptibility-resistance patterns (antibiogram), O serotype
      lipopolysaccharide and chromosomal DNA restriction fragment length polymorphisms
      (RFLP) using a PAK pilin gene probe. Some patients were colonized by isolates
      identical by all three analytical procedures whereas other patients were found
      where multiple isolates were identical on the basis of serotype and antibiogram
      analysis, but different on the basis of RFLP analysis. Examples were found where
      multiple isolates from an individual patient appeared to be identical on the
      basis of serotyping and RFLP data, but different on the basis of antibiogram.
      Strains refractory to O serotyping could be characterized by RFLP type. These
      results indicate that RFLP analysis provides a valuable addition to routine
      serotyping and antibiogram studies on Pseud. aeruginosa isolates and that
      significant numbers of burn patients become co-colonized/co-infected with
      phenotypically diverse strains of this organism.

PMID- 8554687
TI  - Comparison of the effects of nerve growth factor and superoxide dismutase on
      vascular extravasation in experimental burns.
AB  - Superoxide dismutase (SOD), a free-radical scavenger, inhibits the increase of
      vascular permeability in experimental burn lesions in rats. In this study the aim
      was to determine whether Nerve Growth Factor (NGF), which has been implicated in
      the modulation of some inflammatory reactions, behaves in an analogous way. The
      study compares the haematocrit (Ht) and haemoglobin (Hb) variations in three
      groups of rats treated respectively with saline solution, SOD and NGF,
      immediately after causing a 25 per cent dermal burn injury. Statistical
      comparison (Student's t test) of the Ht and Hb variations between the Control
      group (Ht and Hb increase) and the NGF group (Ht and Hb decrease), shows
      significant differences in the intervals between 15 and 60 min (P < 0.01) and
      between 60 and 120 min (P < 0.05). Although SOD is able to control extravasation
      in the immediate postburn period (basal-15 min), NGF has a comparable effect in
      subsequent periods. The overall action of NGF shows that this agent is able to
      maintain Ht and Hb values at basal levels even after 120 min postburn. These
      results seem to be the first evidence of an inhibitory effect of NGF on the
      vascular permeability in burn lesions.

PMID- 8554688
TI  - Salvage of extensively burned upper limbs by a pedicled latissimus dorsi flap.
AB  - Very deep burns of the arm and elbow lead to soft tissue necrosis and infection
      with exposure of important structures. Aggressive debridement should be performed
      as early as possible to cut the vicious circle, and the defect, which may be
      extensive, should be covered by well-vascularized tissues. The reliability and
      versatility of the pedicled latissimus dorsi muscle or musculocutaneous flap make
      it our first choice in the management of this problem. A retrospective study of
      three patients for whom salvage of the upper limb has been achieved by the use of
      a pedicled latissimus dorsi flap is presented, illustrating the advantages of
      this technique.

PMID- 8554689
TI  - Psychological and social aspects of burns.
AB  - Although the literature on the psychological consequences of burns is fairly
      extensive, the evidence gathered by the charity 'Changing Faces' over the last 2
      years suggests that the resources allocated to psychological rehabilitation are
      still far from adequate. This article draws on the personal experience of one of
      the authors who was in a car fire 24 years ago, reviews some of the literature,
      briefly looks at the work done by Changing Faces and discusses some of the tasks
      of the 'burns team'. The authors are aware that generalizations about the
      consequences of burns are fraught with risk because every fire has its own causes
      and complications, but it is hoped that the themes expressed here do raise
      important general points.

PMID- 8554690
TI  - Running Y-V-plasty for burn scar contracture.
AB  - Seventeen patients with 24 regions received running Y-V-plasties to release burn
      scar contractures over a 3-year period. The scar band can be completely
      interrupted and lengthened without the need for undermining and transposition of
      the skin flaps, circulatory embarrassment of the flaps can be avoided. The wound
      morbidity was extremely low, and no recurrence of the contracture was noted
      during follow-up periods. The running Y-V-plasty has unique advantages for the
      treatment of cord-like or linear burn scar contractures. This approach resulted
      in shorter hospital stay and allows early mobilization of the involved
      extremities.

PMID- 8554691
TI  - Burns in young children: a study of the mechanism of burns in children aged 5
      years and under in the Hamilton, Ontario Burn Unit.
AB  - This paper explores the burn agents involved among children admitted to the
      Hamilton General Hospital Burn Trauma Unit (BTU), and the severity of their
      burns. Charts were retrospectively reviewed for all burn cases aged 5 years and
      under admitted to the BTU between January 1986 and mid-November 1990. Descriptive
      statistics and one-way analysis of variance were employed. Of the 52 patients
      aged 5 years and under, two were excluded from the study. The majority (35, 70
      per cent) were aged 2 years and under. The mean burn depth for all patients was
      equivalent to a deep partial thickness burn. Approximately two-thirds of cases
      resulted from either the preparation or consumption of food or hot liquids, while
      the remainder suffered from either flame burns or bath-tub scalds. Children
      burned during food preparation or consumption were younger (mean age 1.8 years)
      than those sustaining flame burns (mean age 2.7 years) (P = 0.02). Of those burns
      sustained from either the preparation or consumption of food, 44 per cent were
      scalds from a cup of hot beverage at the table, 19 per cent were scalds from an
      electric kettle, and an equal number from a coffee or tea pot sitting at the
      table. There was a significant difference in both the mean total body surface
      area of the burn, and the number of days spent in the BTU, according to the agent
      involved (P = 0.01 and P = 0.004, respectively). Flame and contact injuries were
      often the most severe. A disproportionate number of burn victims admitted to
      hospital are infants and toddlers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554692
TI  - Electrical burn caused by contact of radio receiver antenna with overhead cables.
AB  - Two soldiers suffering from electrical burns due to contact of radio receiver
      antenna with overhead cables are presented. The necessary preventive measures for
      such injuries are discussed.

PMID- 8554693
TI  - An unusual case of acute renal failure in burns.
AB  - Nowadays acute renal failure in burns is not a common occurrence, at least not
      when most of the wounds have already healed. We report a case of a 6-year-old
      child with 45 per cent flame burns, who suffered acute renal shutdown 43 days
      after burns when all except 1 per cent of the raw areas had already been grafted
      with autologous skin. There was no identifiable focus of infection and no
      evidence of septicemia. The patient was not receiving any nephrotoxic drugs. The
      child responded well to peritoneal dialysis and recovered fully.

PMID- 8554694
TI  - Impairment of renal function after treatment of a burn patient with diclofenac, a
      non-steroidal antiinflammatory drug.
AB  - Due to pain from infected 12 per cent TBSA flame injuries a 71-year-old female
      was treated with a non-steroidal antiinflammatory drug (diclofenac), thereby
      inhibiting the synthesis of prostaglandins, and developed transient impairment of
      renal function. This case report indicates that prostaglandins may be required to
      modulate the late responses after burns or other major trauma, especially when
      infected.

PMID- 8554695
TI  - Recent references.

PMID- 8554696
TI  - Ophthalmic zoster as a reason for admission into a regional burns unit.

PMID- 8554697
TI  - Regulation of marginal circumferential sutures for tie-over dressings using
      double-sided adhesive tape.

PMID- 8554698
TI  - Detection of T cell receptors in early rheumatoid arthritis synovial tissue.
AB  - Synovial tissue is rarely available from patients with early synovitis, with the
      exception of synovial biopsies. However, T cell populations early in the
      development of synovitis may be enriched in antigen-specific cells and critical
      to disease pathogenesis. To investigate the T cell repertoire in early synovitis,
      we utilized a PCR protocol for detection of T cell receptor (TCR) transcripts
      present in small amounts of synovial tissue. To expand the substrate for PCR,
      preamplification of cDNA was performed with a 3' constant region primer plus
      either a mixture of variable region primers or random hexanucleotides. Utilizing
      this method improved the sensitivity of detection. This technique is applied here
      to the analysis of TCR transcripts in synovial biopsies from individuals with
      early rheumatoid arthritis (RA) and non-RA synovitis. TCR alpha-chain transcripts
      were detectable in 5/5 RA and 4/4 non-RA specimens evaluated, with beta-chain
      transcripts detected in 4/5 early RA and 4/4 non-RA specimens evaluated.
      Confirmation of transcripts by sequencing of cloned PCR products verified the
      specificity of amplification. The most frequently expressed TCR V region families
      in early RA synovitis were V alpha 11, V alpha 14, V alpha 28, V beta 7, V beta 9
      and V beta 17. Several of these V regions have previously been implicated in
      studies of chronic RA synovitis. J alpha and J beta region usage was similar to
      that seen in chronic RA, and conserved N region motifs were apparent. We conclude
      that it is possible to detect TCR transcripts in small synovial biopsies from
      individuals with early arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554699
TI  - Selective inhibition of adhesion molecule expression by edelfosine (ET-18-OCH3)
      on human umbilical vein or microvascular endothelium.
AB  - An abundance of data is accumulating that suggest that if one can block
      endothelial cell-leukocyte binding or inhibit cell adhesion molecules (CAM),
      inflammatory events can be greatly diminished. In this report, we demonstrate
      that an alkyl-lysophospho-lipid compound (ET-18-OCH3) can decrease adhesion
      molecule expression on cultured human micro- and macrovascular endothelial cell
      lines. ET-18 selectively decreased CAM expression; CD31 was decreased, however.
      Vascular CAM-1 tumor necrosis factor-alpha-induced expression was not altered.
      Intercellular adhesion molecule 1 expression was decreased, but endoglin
      expression was not affected. Thus, we have demonstrated nontoxic downmodulation
      of vascular CAM expression in vitro. Whether this compound will have anti
      inflammatory properties needs to be clarified in animal models.

PMID- 8554700
TI  - Protective antitumor immunity induced by immunization with MHC class II gene
      transfected tumor cells is unrelated to MHC class II expression.
AB  - A/JCr mice reject Sa1N fibrosarcoma cells genetically engineered to express major
      histocompatibility complex (MHC) class II molecules and are highly resistant to
      subsequent challenge with unmodified Sa1N cells. In this report we examine the
      mechanism by which this protective antitumor immunity is induced. We found that
      MHC class II antigen-positive tumor cells were no more effective than irradiated,
      MHC class II antigen-negative cells at inducing secondary protective immunity.
      Additionally, therapeutic immunization with MHC class II antigen-positive tumor
      cells had no effect on the growth of admixed Sa1N cells or preexisting Sa1N
      tumors. Based on these observations, we conclude that the MHC class II antigen
      induced immune response is not related to Sa1N-specific antitumor immunity.

PMID- 8554701
TI  - Differing sensitivity of non-hematopoietic human tumors to synergistic anti
      transferrin receptor monoclonal antibodies and deferoxamine in vitro.
AB  - We tested non-hematopoietic human tumors for in vitro sensitivity to either a
      pair of synergistic IgG antitransferrin (Tf) receptor monoclonal antibodies
      (MAbs), deferoxamine (DFO) or the combination thereof. With an equimolar mixture
      of the two MAbs (A27.15, E2.3), two prostate tumors showed similar degrees of
      maximal growth inhibition (PC-3: 35%, DU 145: 38%), two breast tumors showed more
      variability (MDA-MB-231: 26%, SK-BR-3: 52%) and two neuroblastomas showed the
      most variability (SK-N-SH: 4%, SK-N-MC: 76%). When the MAbs were applied together
      with DFO, the D50 for DFO was reduced for all tumors (PC-3: 2.5x, DU 145: 3.7x;
      MDA-MB-231: 2.9x, SK-BR-3: 1.9x, and SK-N-SH: 2.6x, SK-N-MC: 7.0x). Sensitivity
      to MAbs was more closely correlated with the relative decrease in Tf receptor
      density resulting from antibody exposure than with initial receptor density. The
      degree of reduction of D50 for DFO resulting from the joint application with the
      MAbs was, however, most closely related to the growth rate of the tumors. Since
      some non-hematopoietic tumors exhibit sensitivity to the effects of a synergistic
      pair of IgG anti-Tf receptor MAbs and DFO, it appears that further preclinical
      studies with such tumors, especially those with higher Tf densities, would be of
      interest.

PMID- 8554702
TI  - Autoimmune aspects of primary pulmonary hypertension.
AB  - Although primary pulmonary hypertension (PPH) is considered to be an idiopathic
      condition, it has been postulated that autoimmunity may play a role in the
      pathogenesis of the disease. This argument has been based on frequent coexisting
      clinical and serological rheumatic findings. Moreover, approximately in a third
      of the patients with PPH, and antinuclear factor can be detected. Pulmonary
      hypertension may appear as a secondary complication to various autoimmune
      conditions. In light of these findings we examined sera derived from 40 patients
      diagnosed as having PPH for the presence of 18 different autoantibodies by the
      ELISA and immunofluorescent techniques. Of the 40 patients, 62.4% had circulating
      autoantibodies and 47.5% presented with multiantibody responses. Autoantibodies
      most commonly observed were antinuclear (42.5%), anti-ssDNA (25%) and
      antithyroglobulin (30%) antibodies. These results may imply that in a subgroup of
      patients with PPH the disease may be ascribed to an immune dysregulation or
      alternatively that autoantibodies accompany the disease progression as an
      epiphenomenon.

PMID- 8554703
TI  - Autoantibody profile of primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease of
      unknown etiology. It has been suggested that genetic and immunological factors
      are important in its pathogenesis. The present study examined the prevalence of
      23 different autoantibodies in 25 PSC sera, by ELISA, in order to better define
      the autoimmune profile of PSC. The results indicate that 88% of PSC patients
      produced at least 1 autoantibody, and 36% had reactivity to multiple
      autoantibodies. Moreover, 35% of the PSC patients produced anti-endothelial-cell
      antibodies (AECA) and 75% of the sera contained perinuclear antineutrophil
      cytoplasmic antibodies (pANCA), detected by indirect immunofluorescence. The
      prominent ANCA autoantibody was anti-cathepsin-G, demonstrated in 35% of the
      patients. The multiplicity of the autoantibody profile, revealed in the present
      study, points to the autoimmune characteristics of PSC. In addition, the
      association of ANCA and of AECA in PSC may suggest a pathogenic role for these
      antibodies in PSC.

PMID- 8554704
TI  - Comparative studies on vascular endothelium in vitro. 3. Effects of cytokines on
      the expression of E-selectin, ICAM-1 and VCAM-1 by cultured human endothelial
      cells obtained from different passages.
AB  - Endothelial cells (EC) are very responsive to proinflammatory cytokines, e.g.
      interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha), as well as to
      bacterial lipopolysaccharide. EC are stimulated by these substances to secrete
      chemotactic factors and to increase expression of cell adhesion molecules (CAM),
      leading to dramatically altered interactions with leukocytes, e.g. granulocytes
      and monocytes. In these interactions E-selectin, ICAM-1 and VCAM-1 are known to
      play an important role, as they are presented by the EC and interact with
      corresponding ligands on the white blood cell membranes. These adhesion molecules
      have been studied worldwide in a variety of in vitro experiments using cultured
      EC. Different passages and mixtures of passages have been used in these
      experiments, often without any regard to the comparability of the results. In
      this study the expression of E-selectin, ICAM-1 and VCAM-1 on cultured human
      umbilical vein EC (HUVEC) obtained from different passages (passages 1-6) was
      studied after 4, 8 and 24 h of exposure to IL-1 beta and TNF alpha. In previous
      studies, we have shown that IL-1 beta and TNF alpha increase the expression of E
      selectin and ICAM-1 on the cytoplasmatic membranes of HUVEC and human adult EC
      from the saphenous vein and femoral artery in a similar fashion. Using a
      comparative quantitative cell enzyme immunoassay, we found that the expression of
      the adhesion molecules was significantly reduced with increasing passages. There
      was also a decreased persistence of CAM comparing different periods of
      stimulation between 6 and 24 h in the different passages. These data indicate
      that the number of passages plays an important role in the expression of adhesion
      molecules on EC. The results are relevant for the meaningful planning of
      comparative in vitro studies on EC presentation of CAM.

PMID- 8554705
TI  - Interferon-gamma-induced downregulation of CD4 inhibits the entry of human
      immunodeficiency virus type-1 in primary monocytes.
AB  - We have previously shown that the treatment of monocytes with interferon-gamma
      (IFN-gamma) prior to exposure with human immunodeficiency virus type-1 (HIV)
      results in complete inhibition of HIV infection of monocytes. In the present
      report, we have extended this study to obtain information on the mechanism(s)
      underlying IFN-gamma-induced inhibition of HIV infection of monocytes. To examine
      the effect of IFN-gamma on HIV entry, the first event in the infectious cycle of
      the virus, we amplified HIV-gag sequences in the genomic DNA and RNA of IFN-gamma
      treated monocytes, and found no evidence for the presence of either proviral DNA
      or HIV RNA sequences. These results were consistent with the absence of
      intracellular HIV particles either in the latent or actively replicating state as
      determined by flow-cytometric analysis of these cells. Furthermore, no HIV
      induced cytopathic effects, such as multinucleated giant cell formation or cell
      death, were observed in IFN-gamma-treated monocytes after their exposure to HIV.
      Stimulation of IFN-gamma-treated monocytes 6 days postinfection with tumor
      necrosis factor-alpha (TNF-alpha), which is known to augment HIV replication in
      the infected cells, did not result in the induction of the HIV indicating the
      absence of latent HIV infection in IFN-gamma-treated monocytes. Treatment of
      monocytes with IFN-gamma, TNF-alpha, or with a combination of the two agents
      which is known to induce antimicrobial free radical nitric oxide (NO2- in the
      murine system did not induce NO2- production human monocytes suggesting the
      antiviral activity of IFN-gamma to be independent of NO2(-)-mediated killing of
      HIV or HIV-infected monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554706
TI  - Dehydration anorexia in decerebrate rats.
AB  - Hypertonic saline (HS) administered intraperitoneally reduced the intake of
      sucrose solution infused intraorally in tube-fed decerebrate rats, as it did in
      control animals. Similarly, either intraperitoneal or intravenous HS markedly
      decreased the intake of laboratory chow by neurologically intact control rats.
      These observations complement recent findings that lesions of putative
      osmoreceptors in the ventral diencephalon, which eliminate thirst and blunt
      pituitary secretion of vasopressin and oxytocin in response to HS in rats, have
      no apparent effect on the HS-induced inhibition of food intake. Taken together
      they support previous studies indicating an important role for the caudal
      brainstem in the central control of food intake and suggest that such brainstem
      control may also include the inhibition of food intake induced by acute
      hyperosmolality.

PMID- 8554707
TI  - Intact delay-eyeblink classical conditioning in amnesia.
AB  - The status of classical conditioning in human amnesia was examined by comparing
      conditioning of the eyeblink response (the unconditional response) to a tone
      conditioned stimulus (CS) paired with an airpuff unconditioned stimulus (US) in
      the delay paradigm between 7 amnesic and 7 age- and education-matched normal
      control participants. Amnesic patients exhibited normal baseline performance in
      pseudoconditioning and normal acquisition and extinction of conditioned responses
      in terms of the number, latency, and magnitude of eyeblinks. These results
      indicate that in humans, as in rabbits, brain structures critical for declarative
      memory are not essential for the acquisition of elementary CS-US associations.

PMID- 8554708
TI  - The role of the rat hippocampal system in several effects of context in
      extinction.
AB  - The effect of fornix lesions on some effects of manipulating the context on
      performance in extinction were studied. In renewal, subjects' responding to an
      extinguished conditioned stimulus (CS) recovered when the CS was presented in the
      context in which it had been conditioned after extinction in a different context.
      In reinstatement, it recovered when the CS was tested after independent
      presentation of the unconditioned stimulus (US; an effect mediated by contextual
      conditioning.) In spontaneous recovery, it recovered after the passage of time,
      that is, when the CS was tested in a new temporal context. In the conditioned
      suppression method, fornix lesions had no effect on conditioning, extinction,
      renewal, or spontaneous recovery; however, they abolished the reinstatement
      effect. The results suggest that the hippocampal system may be important in the
      formation of context-US associations, but not in other types of learning about
      the context.

PMID- 8554709
TI  - Maze learning and morphology of frontal cortex in adult and aged basal forebrain
      lesioned rats.
AB  - Maze performance and morphology of frontal cortex were assessed in young adult,
      middle-aged, and aged rats with and without lesions of the nucleus basalis
      magnocellularis. Although maze performance did not vary with age, neuron number
      and the thickness of superficial laminae were reduced in aged rats. Lamina II-III
      neurons were hypertrophied in middle-aged rats relative to both younger and older
      groups. At all ages, lesions significantly impaired maze performance. In young
      adult rats, lesions moderately reduced the size of lamina II-III neurons. This
      effect was more pronounced in middle-aged rats. Lesions in aged rats did not
      affect neuron size. The neuronal changes seen in middle-aged rats may reflect a
      compensatory response to the expression of other age-related neuronal changes,
      which may affect the ability of cortical neurons to respond to lesion-induced
      loss of cholinergic input.

PMID- 8554710
TI  - Spatial learning and memory as a function of age in the dog.
AB  - Spatial learning and memory were studied in dogs of varying ages and sources.
      Compared to young dogs, a significantly higher proportion of aged dogs could not
      acquire a spatial delayed nonmatching-to-sample task. A regression analysis
      revealed a significant age effect during acquisition. Spatial memory was studied
      by comparing performance at delay interval of 20, 70, and 110 s. At short delays
      aged and young dogs were similar; at longer delays, errors increased to a greater
      extent in old than in young dogs; however this was not statistically significant.
      It was possible to identify 2 groups of aged animals, age-impaired and age
      unimpaired. Several of the dogs were also tested on an object recognition memory
      task, which was more difficult to learn than the spatial task. The possibility
      that these findings are confounded by breed differences is considered. Overall,
      the present results provide further evidence of the value of a canine model of
      aging.

PMID- 8554712
TI  - Conditioned diminution of the unconditioned response in rabbit eyeblink
      conditioning: identifying neural substrates in the cerebellum and brainstem.
AB  - Several models of Pavlovian conditioning assume that processing of an
      unconditioned stimulus (US) is diminished by a conditioned stimulus (CS) with
      which it had been paired. Two experiments evaluated the hypothesis that US
      processing may be diminished by CS-dependent activation of the cerebellum.
      Experiment 1 showed that electrical brain stimulation (EBS) of the cerebellar
      interpositus nucleus diminished the peak amplitude of the rabbit's unconditioned
      eyeblink response. This effect was bilateral, was systematically related to the
      intensity of EBS, maximal 50 ms after the offset of EBS, and substantially
      reversed by naloxone. Experiment 2 showed that inactivating the contralateral red
      nucleus with gamma-D-glutamylglycine blocked the decremental effect of
      interpositus stimulation. Implications for neural systems mediating the
      inhibitory effects of cerebellar activation and the antinociceptive role of
      noradrenergic and opioid systems in Pavlovian conditioning phenomena are
      discussed.

PMID- 8554711
TI  - Sex differences in learning and memory in mice: effects of sequence of testing
      and cholinergic blockade.
AB  - Sexual dimorphism in spatial and cued navigation using the Morris water maze was
      examined in C57BL/6 mice both with and without administration of scopolamine, a
      cholinergic blocker. In Exp. 1, female and male mice learned to perform first a
      spatial, then a cued, navigation task. Both performed a spatial task similarly;
      males, however, performed a cued task better than females. In Exp. 2, the
      sequence of navigation testing was reversed. Both performed similarly on a cued
      task; however, males performed a spatial task better than females. In both
      experiments, females were more sensitive than males to the effects of
      scopolamine. No significant confounding sex differences were found in either
      spontaneous activity or passive avoidance retention. These data indicate that sex
      differences in spatial and cued tasks are dependent on the sequence of task
      presentation and implicate a role for the cholinergic system in these
      differences.

PMID- 8554713
TI  - Early cerebellar lesions impair eyeblink conditioning in developing rats:
      differential effects of unilateral lesions on postnatal day 10 or 20.
AB  - Experiment 1 demonstrated that the ipsilateral cerebellar hemisphere is essential
      for the acquisition of eyeblink conditioning in infant rats and that cerebellar
      lesions given on Postnatal Day 10 (PND10) produced deficits in eyeblink
      conditioning when given to either hemisphere. For both hemispheres, lesions that
      were restricted to the cerebellar cortex produced less severe deficits than
      lesions that included the deep nuclei. Experiment 2 showed that the age at which
      the cerebellar lesions occurred determined whether damage to the contralateral
      cerebellar hemisphere impaired conditioning. Lesions of either the ipsilateral or
      contralateral hemisphere that included the deep nuclei disrupted eyeblink
      conditioning when given on PND10. In contrast, when lesions were given on PND20,
      ipsilateral lesions that included the deep nuclei abolished conditioning, while
      the same lesion given to the contralateral hemisphere had no effect.

PMID- 8554714
TI  - Specific effects of idazoxan in a distraction task: evidence that endogenous
      norepinephrine plays a role in selective attention in rats.
AB  - Rats were injected with the alpha 2-adrenergic antagonist idazoxan (IDZ) prior to
      testing on vigilance and distraction tasks. In the vigilance task, rats responded
      with nose pokes to brief visual cues presented at variable intervals following
      trial onset. The distraction task was similar except that irrelevant odor cues
      (distractors) were presented in the interval prior to light onset on some trials.
      IDZ injection had no effect on performance in the vigilance task. In the
      distraction task, however, the higher IDZ dose (1.0 mg/kg) modulated the
      propensity to make a premature response when the distractors were presented.
      Notably, the direction of the effect varied with the rats' baseline level of
      distractibility. This pattern of effects suggests that endogenous norepinephrine
      (NE) influences distractibility and/or selective attention.

PMID- 8554715
TI  - Prepulse inhibition in the rat is regulated by ventral and caudodorsal striato
      pallidal circuitry.
AB  - It has been shown that the acoustic startle reflex is inhibited by weak auditory
      prepulses presented 30-500 ms prior to the startling stimulus and that this
      prepulse inhibition (PPI) is modulated by ventral striato-pallidal circuitry.
      However, dorsal striatal modulation of PPI has not been examined. Cell-specific
      lesions and intracerebral drug infusions were used to elucidate striatal
      modulation of PPI. Quinolinic acid lesions of the ventral and caudodorsal
      striatum significantly decreased PPI, whereas lesions of the rostrodorsal and
      middorsal striatum did not significantly alter PPI. Infusion of the GABA-A
      antagonist picrotoxin into the ventral and caudal dorsal pallidum also
      significantly reduced PPI, whereas rostral pallidal picrotoxin infusion had no
      significant effect. Thus, PPI in the rat seems to be modulated by both ventral
      and caudodorsal striato-pallidal circuitry, but not by rostrodorsal or middorsal
      striato-pallidal projections.

PMID- 8554716
TI  - Cocaine enhances the expression of fear-potentiated startle: evaluation of state
      dependent extinction and the shock-sensitization of acoustic startle.
AB  - Cocaine's effects on fear extinction and on the shock-sensitization of acoustic
      startle were examined. Following fear acquisition, rats exposed to the
      nonreinforced conditioned stimulus (CS) after cocaine administration demonstrated
      significant levels of fear-potentiated startle when evaluated in the drug-free
      state. The CS also increased startle amplitudes in subjects extinguished and
      tested with cocaine, indicating that mechanisms other than state-dependent
      learning are involved in the extinction deficit. The presentation of 10
      footshocks augmented acoustic startle, and the shock enhancement was unaffected
      by cocaine preexposure. These data indicate that the aversive consequences of
      footshock relevant to the acquisition of conditional fear are not sensitized by
      the drug. It was suggested that cocaine reinforces fear responding to a
      threatening stimulus.

PMID- 8554717
TI  - Gustatory detection thresholds after parabrachial nuclei lesions in rats.
AB  - Rats with either electrolytic (Experiment 1) or excitotoxic lesions (Experiment
      2) that had been electrophysiologically centered in the gustatory zone of the
      parabrachial nuclei (PBN) were tested for sucrose and NaCl taste detection
      thresholds in a conditioned avoidance task. With 1 exception, all of these rats
      had previously shown severe deficits in acquiring an LiCl-based conditioned taste
      aversion (CTA) to sucrose, NaCl, or alanine. The rats with excitotoxic lesions
      also had failed to express a depletion-induced sodium appetite. Despite the
      uniformity of these deficits, the rats with lesions exhibited varied performance
      in the detectability task. Roughly 1/3 of the rats did not perform competently,
      1/3 had elevated thresholds, and 1/3 showed no or only marginal impairments in
      taste detectability. These findings demonstrate that the elimination of CTA
      following PBN lesions is not necessarily linked to an impairment in taste signal
      detection. Thus, PBN-induced deficits on 1 taste-related task do not entirely
      correspond with impairments on another.

PMID- 8554718
TI  - Time structure of self-grooming in the rat: self-facilitation and effects of
      hypothalamic stimulation and neuropeptides.
AB  - Specific brain manipulations, such as stimulation of the paraventricular nucleus
      of the hypothalamus (PVH) or injections of neuropeptides, increase self-grooming
      in the rat. Such manipulations also affect the different movements that
      constitute grooming. Using models to assess the time structure of these
      movements, the authors demonstrate that the rules that control the time structure
      within grooming are different from the ones that control its initiation. This
      study also showed that grooming is self-facilitating and that different brain
      manipulations in the same hypothalamic area induce structurally different kinds
      of grooming. The authors suggest that this part of the hypothalamus is not only
      involved in setting priorities to grooming, relative to other behaviors, but is
      also involved in the timing of different grooming components. These findings
      suggest that different neural mechanisms may be involved in the initiation and
      internal time structure of grooming.

PMID- 8554719
TI  - Temporal integration in self-stimulation: a paradox lost?
AB  - Seven self-stimulating rats with electrodes located along the medial forebrain
      bundle were used to study how excitation dissipates at the end of a train of
      rewarding electrical pulses. On a 5-s, fixed-interval schedule, the rats pressed
      a lever to obtain 2 trains of pulses separated by gaps of up to 2 s; the first
      train was fixed at a just-subthreshold number of pulses, whereas the second train
      was used to scale the number of pulses needed to just support consistent
      responding. The number of pulses needed grew with increasing gaps between the 2
      trains, rapidly at first and then decelerating to an asymptote, with time
      constants of a few tenths of a second. These results support C. R. Gallistel's
      (1974, 1978) model of leaky integration of rewarding brain stimulation.

PMID- 8554720
TI  - Stimulus-elicited behavior in rapid eye movement sleep without atonia.
AB  - Alert wakefulness (W) and rapid eye movement sleep (REM) are remarkably similar
      on several measures of brain activity, but 2 differences in REM are reduced
      sensory responsiveness and atonia in postural muscles. Pontine tegmental lesions
      create REM without atonia (REM-A), releasing motor behavior. In 9 cats, we
      studied the acoustic startle reflex (ASR), orienting (OR), and ponto-geniculo
      occipital waves (PGOE) elicited by tones during W, REM, REM-A, and non-REM
      (NREM). OR occurred in W and REM-A, being most complete in cats with the most
      elaborate spontaneous behavior. ASR occurred in W, NREM, and REM-A in lesioned
      cats. In normal cats, ASR rarely appeared in NREM and REM. PGOE had similar
      characteristics in both groups. The similarity of REM to W is particularly
      obvious when cats lack motoneuronal inhibition.

PMID- 8554721
TI  - Interfering with somatosensory stimulation from pups sensitizes experienced,
      postpartum rat mothers to oxytocin antagonist inhibition of maternal behavior.
AB  - Proximal separation (PS) refers to isolating pups in small cages so dams can
      hear, smell, and see pups but have very limited physical contact with them. Six
      days of PS diminished the number of discernible oxytocin- (OT) immunostaining
      perikarya in forebrain areas of rat dams compared with 6 days of total separation
      (TS) or no separation (NS) from pups. Dams exhibited a more rapid resurgence of
      maternal behavior after 4-6 days of PS than after 4-6 days of TS. Bilateral
      infusion of the OT antagonist (OTA; 1 microgram/microliter/side) into the ventral
      tegmental area blocked the resurgence of maternal behavior after 3-6 days of PS
      but not after 2 days of PS or 4-6 days of NS. The conclusion was that PS for 3 or
      more days reinstates OT as necessary and sufficient for the activation of
      maternal behavior in experienced rat mothers. These findings suggest that some
      aspects of somatosensory stimulation from pups regulate the role of OT in the
      control of maternal behavior.

PMID- 8554722
TI  - Cholecystokinin changes the duration but not the rate of licking in vagotomized
      rats.
AB  - Abdominal vagotomy markedly reduces or abolishes the inhibitory effect of
      cholecystokinin (CCK-8) on meal size. To investigate the rate and microstructure
      of licking underlying this phenomenon, licking was measured throughout a meal of
      milk in intact and vagotomized rats after intraperitoneal injections of isotonic
      saline or CCK-8. CCK-8 increased the slope of the decay of licking, decreased the
      efficiency of licking, and decreased the duration of licking in intact rats but
      had no effect on either the slope of the decay of licking or the efficiency of
      licking, but it increased the duration of licking in vagotomized rats. These
      results demonstrate that abdominal vagal nerves are necessary for CCK-8 to
      increase the rate of decay of licking, but nonvagal mechanisms mediate the effect
      of CCK-8 on duration of licking.

PMID- 8554723
TI  - Excitotoxic lesions of the parabrachial nuclei prevent conditioned taste
      aversions and sodium appetite in rats.
AB  - Electrolytic lesions of the parabrachial nuclei (PBN) disrupt conditioned taste
      aversion (CTA) in the rat, but it is not known whether this effect is due to
      damaging axons of passage or to destruction of intrinsic neurons. We tested 10
      rats with electrophysiologically guided, ibotenic acid lesions of the PBN (PBNx)
      to determine whether they could acquire a LiCl-induced CTA to l-alanine (0.3 M)
      or demonstrate a sodium appetite following furosemide treatment and overnight
      access to sodium deficient chow. Vehicle-treated and nonsurgical controls were
      included in the design. PBNx rats failed to develop a CTA, even after 3
      conditioning trials. Moreover, more than 8 months later, a subset of the PBNx
      rats were again unable to learn a CTA using NaCl as the conditional stimulus
      (CS). After the furosemide treatment, the control rats drank an average of 20.3
      ml of strong salt in 24 hr. The PBNx rats drank virtually no NaCl during the
      first 2 hr and averaged only 4.0 ml in 24 hr. In the PBN, damage to neuronal
      somata is more critical than interrupting fibers of passage for producing
      deficits in taste-guided behaviors.

PMID- 8554724
TI  - The crystal structure of waxes.
AB  - Quantitative electron crystallographic studies have been carried out on
      epitaxially oriented multi-component waxes. Intensities from two paraffin-based
      samples, an artificial six-component medium wax (equimolar distribution of chain
      lengths) and a petroleum-based wax (Gaussian distribution of chain lengths) have
      been used to determine their crystal structures. As found earlier for binary
      paraffin solid solutions, differences in molecular volume are compensated by
      longitudinal molecular shifts within individual lamellae. Nevertheless, each
      lamellar surface must remain flat enough, and with enough crystallographic order
      intact, to nucleate the next lamella, thus accounting for the observed long-range
      correlation in these crystals. Recrystallized beeswax also has a layer packing
      somewhat similar to the paraffin waxes. However, in this case, the lamellar order
      is 'frustrated' so that a certain amount of 'nematically' ordered material must
      be present, spanning the nascent lamellar interfaces.

PMID- 8554725
TI  - Electrostatic properties of beta-cytidine and cytosine monohydrate from Bragg
      diffraction.
AB  - The charge-density distribution in the crystal structure of the nucleoside beta
      cytidine at 123 K has been determined from X-ray diffraction data (Ag K alpha,
      lambda = 0.5608 A) using all 7233 reflections with sin theta/lambda < or = 1.14 A
      1. Maps of electrostatic potential for the cytosine base in cytidine are similar
      to those derived from previous charge-density studies of cytosine monohydrate and
      1-beta-D-arabinosyl-cytosine, after taking chemical differences into account.
      These results were obtained from pseudoatom multipole refinements including kappa
      as a variable to describe the expansion or contraction of the spherical valence
      shell for each atom type. A new structure refinement of this type has also been
      carried out for cytosine monohydrate. A survey of kappa values for hydrogen
      indicates that this is a variable which is not well determined experimentally.
      Variations in kappa H are relayed into the population parameters obtained for
      other pseudoatoms and can have a small but significant effect on molecular
      properties, such as the dipole moment. Assuming an average theoretical value of
      kappa H = 1.24, the molecular dipole moments calculated from the monopole and
      dipole pseudoatom population parameters are 17 (4) and 8.2 (15) Debye for
      cytidine nucleoside and cytosine in the monohydrate, respectively. Systems of
      atomic point charges are presented for cytidine, cytosine and water. These are
      generally satisfactory in reproducing the experimentally determined molecular
      electrostatic potentials and dipole moments.

PMID- 8554726
TI  - Structures of quinoxaline antibiotics.
AB  - The crystal structures of three quinoxaline antibiotics-echinomycin 2QN, triostin
      C and the C222(1) form of triostin A--have been determined, and the structure of
      the P2(1)2(1)2(1) form of triostin A has been re-refined against our previously
      reported data. The molecular conformations are compared with those deduced from
      NMR data and those reported for two complexes of triostin A with
      oligonucleotides. Although the depsipeptide ring conformations are basically
      similar, the effective twofold molecular symmetry is violated by the folding of
      one of the quinoxaline chromophores in echinomycin 2QN and by a rotation of one
      of the ester planes with the formation of an intramolecular hydrogen bond in
      triostin C. In the oligonucleotide complexes of triostin A the chirality of the
      disulfide bridge is inverted. The alanine NH groups are involved in
      intermolecular hydrogen bonds in all four structures, and (except in echinomycin
      2QN) the stacking of the chromophores in the crystal emulates the intercalation
      involved in DNA complex formation. In echinomycin 2QN, the antibiotic molecules
      are hydrogen bonded to form a helix along the crystallographic 6(5) screw axes,
      with a channel of disordered solvent running through the middle of the helix.
      Crystal data: (1), echinomycin 2QN, C53H66N10O12S2.2.5(C3H6O).2.5(H2O), M(r) =
      1289.5, hexagonal, P6(5), a = b = 22.196(15), c = 24.64 (2) A, V = 10,513 (13)
      A3, Z = 6, Dx = 1.222 Mg m-3, lambda (Cu K alpha) = 1.5418 A, mu = 1.275 mm-1, T
      = 193 K, R = 9.0% for 4828 I > 2 sigma (I) and 11.8% for all 7102 unique
      reflections; (2), triostin C, C54H70N12O12S2.0.67(CHCl3).0.67(H2O), M(r) =
      1234.2, orthorhombic, P2(1)2(1)2(1), a = 16.054 (8), b = 17.128 (9), c = 22.706
      (12) A, V = 6244 (6) A3, Z = 4, Dx = 1.313 Mg m-3, lambda (Mo K alpha) = 0.71073
      A, mu = 0.239 mm-1, T = 188 K, R = 7.7% for 4678 I > 2 sigma (I) and 14.0% for
      all 7260 unique reflections; (3), triostin A, C50H62N12O12S2.2(C7H14O2), M(r) =
      1347.6, orthorhombic, P2(1)2(1)2(1), a = 20.94 (2), b = 18.53 (2), c = 18.80 (2)
      A, V = 7292 (13) A3, Z = 4, Dx = 1.228 Mg m-3, lambda (Cu K alpha) = 1.5418 A, mu
      = 1.245 mm-1, T = 293 K, R = 6.8% for 2116 I > 2 sigma (I) and 9.3% for all 2928
      unique reflections; (4), triostin A, C50H62N12O12S2.HCl.2(C3H7NO), M(r) = 1269.9,
      monoclinic, C222(1), a = 10.622 (10), b = 17.035 (17), c = 35.21 (3) A, V = 6371
      (10) A3, Z = 4, Dx = 1.324 Mg m-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.199 mm
      1, T = 153 K, R = 7.5% for 2164 I > 2 sigma (I) and 13.2% for all 3402 unique
      reflections. Extensive use was made of restraints on the geometrical and
      displacement parameters in the successful anisotropic refinement of these
      structures against weak data.

PMID- 8554727
TI  - Polymorphism in ALDH2-genotype in Japanese men and the alcohol-blood pressure
      relationship.
AB  - Aldehyde dehydrogenase with a low Michaelis constant (Km), ALDH2, is a major
      enzyme involved in the conversion of acetaldehyde, a toxic metabolite of ethanol,
      into acetic acid in the liver. Inherited deficiency of ALDH2 activity is found in
      half of Japanese, and is characterized by "Oriental flushing" after alcohol
      consumption. The aim of the present study is to evaluate the influence of the
      genetic polymorphism in alcohol metabolism on the sensitivity to the pressor
      effect of alcohol. Genotypes of ALDH2 were determined in 403 middle-aged Japanese
      men using genomic DNA extracted from white blood cells. Two hundred and forty
      three (60%) of the subjects were shown to be homozygotes for the normal ALDH2
      gene, 25 (6%) of the subjects were homozygotes for the mutant ALDH2 gene, and the
      remaining 135 (33%) were heterozygotes. None of the homozygotes for the mutant
      gene drank enough to show the pressor effect of alcohol. Elevations of blood
      pressure associated with increasing alcohol consumption or with elevations of
      serum gamma-glutamyl transpeptide (GTP) level were not different between the
      other two ALDH2-genotypes. It can be concluded that polymorphism in the ALDH2
      genotype found in Japanese men does not affect the individual sensitivity to the
      pressor effect of alcohol.

PMID- 8554728
TI  - Lewis phenotypes and the insulin resistance syndrome in young healthy white men
      and women.
AB  - An increased risk of ischemic heart disease in men with the Lewis blood group
      phenotype Le(a-b-) has been reported. It has been suggested that the Le(a-b-)
      phenotype is a genetic marker of the insulin resistance syndrome. To examine
      whether Le(a-b-) confers the insulin resistance syndrome, we studied a random
      sample of unrelated healthy young white men and women living in Copenhagen (n =
      380, 18 to 32 years). All individuals had their insulin sensitivity estimated
      using Bergman's minimal model (intravenous glucose in combination with
      tolbutamide) and systolic blood pressure (SBP) was measured with a London School
      of Hygiene Sphygmomanometer. A number of anthropometric measurements including
      body mass index (BMI, kilograms/meters squared) and biochemical characteristics
      were performed. The Lewis blood group typing was carried out on erythrocytes.
      Twenty-one men had the Le(a-b-) phenotype. Compared to all other men (N = 165),
      the Le(a-b-) men had a significantly higher SBP (6 mm Hg, P = .0024). They also
      had higher values of BMI (8%, P = .016), total body fat mass (25%, P = .015),
      fasting values of serum insulin (32%, P = .006), serum C-peptide (20%, P = .029),
      and plasma glucose (8%, P = .003). The fasting values of serum lipids,
      plasminogen activator inhibitor (PAI-1) activity, tissue plasminogen activator (t
      PA) antigen, and insulin sensitivity did not differ between Le(a-b-) men and men
      with other Lewis phenotypes. Altogether 194 women participated in the study of
      which 21 women had the Le(a-b-) phenotype. Except for a lower PAI-1 activity
      (45%, P = .044), no values differed between Le(a-b-) women and women with other
      Lewis phenotypes. The women were also stratified according to use of oral
      contraceptives. Le(a-b-) women using oral contraceptives (N = 8) had a
      significantly lower plasma level of fasting PAI-1 activity (P = .029) and t-PA
      antigen (P = .004) compared to women using oral contraceptives without the Le(a-b
      ) phenotype (N = 42). Our data support the hypothesis that Le(a-b-) men exhibit
      features of the insulin resistance syndrome, including higher levels of BMI, SBP,
      and fasting levels of serum insulin and plasma glucose. In young women no signs
      of the insulin resistance syndrome were found in subjects with the Le(a-b-)
      phenotype.

PMID- 8554729
TI  - Effect of weight loss on blood pressure and insulin resistance in normotensive
      and hypertensive obese individuals.
AB  - In this study, the effect of weight loss on blood pressure and various facets of
      glucose and insulin metabolism was examined in 22 subjects with mild to moderate
      obesity; 11 with high blood pressure (diastolic blood pressure > 95 mm Hg) and 11
      with normal blood pressure (diastolic blood pressure < 90 mm Hg). The two groups
      were similar in mean (+/- SEM) body mass index at baseline (30.2 +/- 1.0 v 31.6
      +/- 1.1 kg/m2), and each group lost approximately 8 kg during the 3-month study
      period. Blood pressure fell significantly (P < .003) following the 8 kg weight
      loss in both the normotensive (122 +/- 3/81 +/- 3 to 110 +/- 3/74 +/- 2 mm Hg)
      and hypertensive (149 +/- 3/98 +/- 1 to 135 +/- 3/86 mm Hg) subjects.
      Furthermore, the plasma glucose and insulin responses to a 75 g oral glucose load
      were significantly lower (P < .001) following weight loss. Finally, insulin
      resistance, as assessed by determining the steady-state plasma glucose (SSPG)
      concentration at the end of a 180 min infusion of somatostatin, insulin, and
      glucose, was also lower (P < .002) after the 8 kg weight loss in the normotensive
      (243 +/- 23 to 172 +/- 15 mg/dL) and hypertensive subjects (266 +/- 18 to 181 +/-
      25 mg/dL). Since the steady-state plasma insulin concentrations were, if
      anything, slightly lower after weight loss in both groups, the lower post-weight
      loss SSPG values actually underestimate the improvement of insulin resistance.
      Thus, weight loss of 8 kg in moderately obese individuals leads to significant
      decreases in blood pressure and plasma glucose and insulin concentrations in
      response to an oral glucose challenge and degree of insulin resistance.

PMID- 8554730
TI  - An in-depth examination of the excretion of albumin and other sensitive markers
      of renal damage in mild hypertension.
AB  - In an in-depth examination to better define the renal effects of mild
      hypertension, we used urinary proteins to indicate damage to the glomerulus
      (albumin), tubular reabsorption capability (retinol-binding protein), and
      turnover of tubular tissue (alanine aminopeptidase and N-acetyl-beta-D
      glucosaminidase) in a group of 18 people with mild hypertension not associated
      with diabetes and a control group (n = 12). The participants' activity was
      controlled on a high normal salt diet for 3 days followed by a low salt diet for
      4 days. Two distinct patterns of albumin excretion were evident in the
      hypertensive group: 22% had elevated, highly variable excretion patterns, and the
      rest had tightly grouped values below 16 mg/g creatinine, 16 micrograms/min, or
      16 mg/L, with the lowest within-person biological variability given by albumin
      calculated as a ratio to creatinine. Albumin and NAG excretion primarily
      correlated with systolic blood pressure and the best correlations were given by
      ratios to creatinine. A marked decrease in salt excretion of 71% (to 50.8
      mEq/day) resulted in significant (P < .0005) decreases in systolic (13.9 mm Hg),
      diastolic (6.4 mm Hg), and mean arterial pressures (8.9 mm Hg) only in the group
      with mild hypertension. However, albumin excretion did not decrease when dietary
      salt content was lowered. The group with hypertension also had higher urinary
      excretion of lysosomal N-acetyl-beta-D-glucosaminidase (P < .01), and whites in
      the group had a higher excretion of retinol-binding protein than did whites in
      the control group (P < .02). Retinol-binding protein values, however, were within
      the normal range, indicating that the elevated albumin values were the result of
      changes in selectivity of the glomerulus.

PMID- 8554731
TI  - Comparison of fourth and fifth Korotkoff diastolic blood pressures in 5 to 30
      year old individuals. The Bogalusa Heart Study.
AB  - The use of fourth phase Korotkoff sound (K4) versus fifth phase Korotkoff sound
      (K5) for the determination of diastolic blood pressure (DBP) has been a subject
      of controversy since the indirect method of determining arterial blood pressure
      was described. Using data from the Bogalusa Heart Study, we evaluated the
      differences between K4 and K5 (K4-K5) from 4633 subjects 5 to 30 years of age
      examined between 1987 and 1991. The overall mean difference between K4 and K5 was
      9.9 +/- 5.6 mm Hg (mean +/- SD). The average difference was highest in 5 to 8
      year olds, where it measured 12.3 +/- 5.5 mm Hg. The average K4-K5 difference
      fell with increasing age and reached a value of 6.3 +/- 2.6 mm Hg by 25 years of
      age. For all race/sex groups, the youngest two age groups differed statistically
      from the oldest age groups in K4-K5 difference (P < .006). There were significant
      differences between blacks and whites (P < .015) and between men and women (P <
      .001) for subjects between 13 and 17 years of age. Additional analyses were
      performed with individuals having K5 = 0 added to yield an expanded population of
      5117 persons. Overall, 9.5% had at least one of six measurements of K5 = 0 and
      most were young subjects: 27% of children 5 to 8 years and 13% of children 9 to
      12 years. We conclude that by age 15 there may be no relevant clinical difference
      in K4-K5. However, in children, K4 and K5 should be recorded and K4 is a more
      reproducible measure of diastolic blood pressure.

PMID- 8554732
TI  - Effect of acute and chronic losartan therapy on active and inactive renin and
      active renin glycoforms.
AB  - Plasma active renin consists of multiple glycoforms, which are differentially
      stored and secreted by the kidney, have varying plasma half-lives, and appear to
      have differing effects on renal sodium and water metabolism. Acute stimulation of
      renal renin secretion results in a disproportionate increase in plasma
      concentrations of the less negatively charged renin glycoforms and a decrease in
      the plasma half-life of active renin. The effects of chronic stimulation have not
      been well studied. We studied the effect of acute and chronic (42 days)
      stimulation of the renin angiotensin system with the AT1 selective angiotensin II
      receptor antagonist losartan on plasma active renin, active renin glycoforms
      separated by isoelectric focusing, and inactive renin in 11 essential
      hypertensive patients. A single 50 mg dose of losartan significantly increased
      plasma active renin concentration (ARC) from a pretreatment baseline of 3.2 +/-
      1.1 to 7.2 +/- 2.3 ng AI/mL/h, 4 h postdose. This was primarily due to an
      increase in plasma concentrations of the less negatively charged active renin
      forms. After 42 days of losartan monotherapy, plasma ARC at losartan trough had
      increased significantly to 7.8 +/- 3.1 ng AI/mL/h, although the proportions of
      active renin forms were identical to baseline. Plasma ARC also increased
      significantly from 7.8 +/- 3.1 to 14.9 +/- 6.0 ng AI/mL/h acutely after the
      losartan dose on day 42 primarily due to increased plasma concentrations of less
      negatively charged active renin forms. Although plasma inactive renin
      concentrations did not change acutely after losartan dosing on day 1 or 42 they
      did increase from 27.3 +/- 7.8 before losartan day 1 to 37.0 +/- 13.7 ng AI/mL/h
      (P = .14) before losartan day 42. Thus, both acute and acute on chronic
      stimulation of renal renin secretion increased circulating ARC and shifted the
      profile of circulating renin toward the less negatively charged forms but did not
      change inactive renin concentrations. Chronic stimulation of renal renin
      secretion with losartan increased plasma concentrations of both active and
      inactive renin, but did not alter the proportions of active renin forms. Since
      the less negatively charged active renin forms have relatively short plasma half
      lives, acute, but not chronic renal renin secretion is associated with a change
      in plasma renin half-life. Chronic stimulation of renal renin secretion with
      losartan presumably increased renin gene expression and resulted in increased
      constitutive secretion of inactive renin, increased constitutive secretion of
      negatively charged active renin forms, and increased renal storage of less
      negatively charged renin forms that were then available for acute regulated
      release.

PMID- 8554733
TI  - The effectiveness and safety of low dose pravastatin in elderly hypertensive
      hypercholesterolemic subjects on antihypertensive therapy.
AB  - To evaluate the efficacy and safety of low dose (10 mg) pravastatin in
      hypercholesterolemic, hypertensive elderly subjects undergoing antihypertensive
      treatment, a randomized, double-blind, placebo-controlled 6-month trial was
      conducted. The subjects had a total plasma cholesterol of at least 250 mg/dL and
      had been, for at least 3 months, consuming a standard lipid-lowering diet
      (American Heart Association Step 1 Diet). Sixty elderly hypertensive patients
      randomly received placebo (n = 30) or pravastatin (n = 30) treatment. The dosage
      consisted of 10 mg of pravastatin daily during the 6-month trial. Over that
      period, in the pravastatin group, plasma levels of total cholesterol and LDL
      cholesterol significantly (P < .01) dropped (-20% and -25%, respectively)
      compared to the placebo group. The plasma level of HDL-cholesterol increased
      (+5%) while triglycerides slightly decreased (-8%) (P < .05). No serious side
      effects occurred, and pravastatin was generally tolerated. Fasting
      hyperinsulinemia (11.0 +/- 0.8 v 9.3 +/- 0.7 microU/mL; P = .06) also improved,
      although not significantly, after 6 months of pravastatin therapy. Results from
      this study confirmed that a low dose (10 mg) of pravastatin daily is a safe and
      effective method of reducing plasma total and LDL-cholesterol in
      hypercholesterolemic, hypertensive elderly patients who are on concurrent
      antihypertensive drug therapy.

PMID- 8554734
TI  - Angiotensins differentially activate phospholipase D in vascular smooth muscle
      cells from spontaneously hypertensive and Wistar-Kyoto rats.
AB  - We previously showed that angiotensin (Ang) II activates phospholipase D (PLD)
      through AT1 receptors in vascular smooth muscle cells (VSMC) isolated from
      Sprague-Dawley rats [Freeman and Tallant, Biochem J. 304:543-548, (1994)]. In the
      present study, we compared activation of PLD by angiotensin peptides in VSMC from
      spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar
      Kyoto (WKY) rats. Ang II caused a dose-dependent increase in PLD activity in VSMC
      from both rat strains. However, the response to Ang II in VSMC from hypertensive
      rats was approximately three times higher than that observed in VSMC from
      normotensive controls. Furthermore, Ang II-induced activation of PLD in VSMC from
      hypertensive rats was significant within 1 min, whereas significant increases in
      PLD activity in cells from normotensive rats were not seen until 10 min after
      exposure to Ang II. Ang-(2-8) caused a similar increase in PLD activity which was
      three times higher in SHR VSMC than in WKY controls. In contrast, Ang-(1-7) did
      not affect PLD activity in either smooth muscle cell population. The Ang II
      mediated increases in PLD activity in VMSC from both rat strains were completely
      blocked by AT1 receptor antagonists (EXP 3174 or L-158,809). Conversely, the AT2
      receptor antagonist PD 123177 (1 mumol/L) was ineffective. Thus Ang II
      stimulation of PLD in VSMC derived from both the hypertensive and normotensive
      rat aorta and the accumulation of its metabolites (e.g., phosphatidic acid and
      diacylglycerol) is coupled to activation of AT1 receptors predominantly and
      occurs in response to Ang II or Ang-(2-8) but not Ang-(1-7). Moreover, activation
      of PLD by angiotensins in VMSC from the SHR is significantly more robust than
      that observed in VSMC from the normotensive WKY rat. We conclude that increased
      activation of PLD by Ang II in genetically-induced hypertension may reflect an
      additional mechanism linking enhanced contractile responses to enhanced growth.

PMID- 8554735
TI  - Applied pressure modulates mesangial cell proliferation and matrix synthesis.
AB  - Substantial in vivo evidence suggests a significant role for glomerular capillary
      pressure in the pathogenesis of progressive glomerulosclerosis. One presently
      available in vitro system allows one to study cells while undergoing stretch.
      However, no comparable system is available to allow one to study in an in vitro
      system how direct application of pressure to glomerular mesangial cells might
      result in the development of glomerulosclerosis. We constructed a pressure
      chamber in which mesangial cells could be subjected to an applied pressure by
      means of a roller pump and adjustable outlet valve. Mesangial cells were grown
      either under control conditions or under an applied pressure of 40 to 50 mm Hg
      corresponding to physiologic intraglomerular pressure. Application of pressure
      significantly decreased mesangial cell number in prolonged culture though no
      discernable effect on cell proliferation could be detected after only short-term
      exposure. Long-term exposure to increased pressure significantly enhanced
      mesangial cell [3H] proline incorporation, a marker for synthesis of the matrix
      component collagen, an event considered to be a precursor to the development of
      glomerulosclerosis. Mesangial cell matrix synthesis was significantly greater for
      cells subjected to 50 to 60 mm Hg pressure compared to 40 to 50 mm Hg pressure.
      Secretory products from macrophages subjected to 40 to 50 mm Hg of applied
      pressure were found to significantly enhance mesangial cell proliferation
      compared to secretory products from macrophages grown under normal pressure. The
      enhancement of mesangial cell matrix synthesis by pressure could not be
      attributed to any change in partial pressure of oxygen in the media nor pH. These
      data suggest that the direct application of pressure to mesangial cells may
      result in the development of glomerulosclerosis by increasing mesangial cell
      matrix synthesis. These in vitro data support a role for glomerular capillary
      pressure in the pathogenesis of progressive glomerulosclerosis.

PMID- 8554736
TI  - Pharmacological properties of endothelins and big endothelins in
      ketamine/xylazine or urethane anesthetized rats.
AB  - Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor peptide formed through
      a specific conversion of its intermediate precursor, big ET-1, by an endothelin
      converting enzyme (ECE). The present study evaluates the capacity of the ECE to
      convert the three big endothelins (big ET-1, big ET-2, and big ET-3), by
      comparing the pressor responses to these peptides with those induced by their
      respective metabolites (ET-1, -2, and -3) in the rat in vivo, anesthetized either
      with a mixture of ketamine/xylazine or with urethane. The mean basal arterial
      pressure under urethane anesthesia was not significantly different from that of
      ketamine/xylazine-treated animals (90/15 mg/kg; intramuscularly), although the
      basal heart rate was significantly higher in the former animals (urethane: 407 +/
      10 beats/min, ketamine/xylazine: 276 +/- 4 beats/min, P < .01; n = 8 to 17). In
      ketamine/xylazine and hexamethonium-treated rats (5-min infusion, 10 mg/kg
      intravenously), intravenous injection of ET-1 (1 nmol/kg) and big ET-1 (1
      nmol/kg) induced potent vasopressor effects which lasted for more than 20 min. ET
      2 (1 nmol/kg) produced similar pressor responses while big ET-2 (1-37) and big ET
      2 (1-38) were twofold less potent than ET-2 (P < .05; n = 3 to 4). Big ET-3
      induced a pressor effect only at 4 nmol/kg and was found to be at least 10 times
      less potent than ET-3. In animals anesthetized with urethane (1.5 g/kg
      intraperitoneally), the pressor responses induced by the endothelins and their
      intermediate precursors, as well as the pressor responses to angiotensin II and
      norepinephrine, were reduced by more than 60% (P < .01) when compared to
      ketamine/xylazine-treated animals. Big ET-3 was found inactive under urethane
      anesthesia. Ganglion blockade by hexamethonium did not affect the response to ET
      1, big ET-1, ET-3, or big ET-3 in rats anesthetized with either ketamine/xylazine
      or urethane. On the other hand, big ET-2 (1-38), in contrast to ET-2 or big ET-1,
      did not release prostacyclin from the rat perfused lung, thus indicating that big
      ET-2 (1-38) is poorly converted in the pulmonary vasculature, and that the
      phosphoramidon-sensitive ECE responsible for the pressor effects of big ET-2 is
      localized elsewhere in the systemic circulation. Our results also show that the
      choice of anesthetics is crucial for the proper monitoring of the pressor
      responses to endothelins as well as other pressor agents. Nonetheless, even in
      what we consider as optimal conditions of anesthesia (threshold dose for the
      pressor response to ET-1 in ketamine/xylazine-treated rats: 0.01 nmol/kg), big ET
      3 remains far less active than big ET-1 as a pressor peptide in the rat,
      suggesting a preferential processing of the latter by the ECE.

PMID- 8554737
TI  - Prolonged endothelin blockade prevents hypertension and cardiac hypertrophy in
      stroke-prone spontaneously hypertensive rats.
AB  - The cardiovascular consequences of endothelin (ET) blockade with the ETA-receptor
      antagonist FR 139317 were evaluated by determining the long-term effects of the
      drug on hemodynamic, hormonal, renal and structural parameters in stroke-prone
      spontaneously hypertensive rats (SHR-SP). Young SHR-SP on a high-sodium diet
      develop malignant hypertension accompanied by renovascular and cerebrovascular
      lesions. In control SHR-SP the systolic blood pressure increased from 196 +/- 3
      to 260 +/- 4 mm Hg, whereas in animals treated with FR 139317 (20 mg/kg
      intraperitoneally, twice daily) it increased only from 196 +/- 4 to 212 +/- 3 mm
      Hg during a treatment period of 6 weeks. There was also an increase in heart
      weight. At the end of the experiment the plasma levels of atrial natriuretic
      peptide and brain natriuretic peptide were significantly lower in the group
      treated with FR 139317 than in the controls. The endothelin plasma levels were
      significantly higher and the plasma renin activity was lower in the group treated
      with the endothelin receptor antagonist. These data indicate that endothelin is
      involved in the maintenance of high blood pressure and cardiac hypertrophy in
      malignant hypertension, as exemplified by SHR-SP.

PMID- 8554738
TI  - Sodium ions attenuate the inhibitory effects of neuropeptide Y on norepinephrine
      release in rat hypothalamus.
AB  - Neuropeptide Y (NPY) has a wide and specific distribution both in the central and
      peripheral nervous systems. In the present study, we have investigated the
      effects of NPY on norepinephrine release in rat hypothalamus, and further
      examined the interaction of NPY with alpha 2-adrenergic receptors, as well as the
      influence of sodium ions on the modulation of norepinephrine release. In an in
      vitro study, NPY significantly inhibited the stimulation-evoked norepinephrine
      release from hypothalamic slices in a dose-dependent manner. The alpha 2
      adrenergic receptor agonist, UK 14,304, also reduced the stimulation-evoked
      norepinephrine release. A low concentration of NPY, which had no effects on its
      own, significantly potentiated the inhibitory effect of UK 14,304 on the
      stimulation-evoked [3H]norepinephrine release. The blockade of alpha 2-adrenergic
      receptors by RX 781094 diminished the inhibitory effects of NPY on norepinephrine
      release. Pretreatment of slices with pertussis toxin (a potent inhibitor of the
      Gi-proteins) significantly attenuated the suppressive effects of NPY and UK
      14,304 on norepinephrine release. When the sodium concentration of the perfusion
      medium was increased, the inhibitory effects of NPY and UK 14,304 on
      norepinephrine release were significantly reduced. These results show that NPY
      might inhibit norepinephrine release that is partially mediated by alpha 2
      adrenergic receptors and the pertussis toxin-sensitive Gi-proteins in rat
      hypothalamus. Moreover, less suppressive effects of NPY and UK 14,304 on
      norepinephrine release in the presence of excess sodium ions suggest that sodium
      ions might actively participate in regulating the NPY and alpha 2-adrenergic
      receptor mediated functions in the central nervous system.

PMID- 8554739
TI  - Immunopathogenic mechanisms in hypertension.
AB  - There is a growing interest in immunologically-mediated lesions in the
      cardiovascular system, as there has been evidence that there are
      antimitochondrial antibodies (AMA) in patients with hypertrophic cardiomyopathy
      or hypertensives with left ventricular hypertrophy (LVH). We have also very
      recently published findings from our laboratory that hypertensives with LVH have
      a considerable quantity of anticardiac antibodies (ACA) in their serum. The aim
      of this study was to investigate the possible involvement of autoimmune
      mechanisms in the pathogenesis and evolution of hypertensive disease. Three
      groups of subjects were included in the study. Group A comprised 37 patients (20
      men, 17 women, mean age 50.5 +/- 8.5 years) with mild to moderate essential
      hypertension, 19 without echocardiographic evidence of LVH, and 18 with LVH.
      Group B comprised 10 patients (6 men, 4 women, mean age 45.1 +/- 8.7 years) with
      secondary hypertension. The control group (C) comprised 15 normotensive subjects
      (8 men, 7 women, mean age 47.7 +/- 8.7 years). Cellular immunity against arterial
      wall antigen was studied in all subjects by means of migration inhibitory factor
      (MIF) against relevant antigen preparation. Sera from Group A and C subjects were
      tested for the presence of autoantibodies against both specific (myocardial) and
      nonspecific antigens, by means of the indirect immunofluorescence technique.
      Eighty per cent of patients with essential hypertension showed a positive
      cellular response (MIF) against an arterial wall antigen compared to the patients
      with secondary hypertension or the control group. Moreover, patients with
      essential hypertension and LVH had the highest incidence of specific
      (anticardiac, ACA) and nonspecific autoantibodies and the highest C3c and C4
      complement component levels compared to patients without LVH or the control
      group. Most of the ACA positive patients were also AMA positive, while the ACA
      negative patients were AMA negative as well. Defects in cell-mediated immunity
      against arterial wall antigen(s) may be the cause or the effect of hypertension.
      On the basis of our findings that there was no delayed type hypersensitivity
      response to arterial wall antigen(s) in the patients with secondary hypertension,
      we suggest that, in some cases of essential hypertension, delayed
      hypersensitivity reactions possibly contribute to the pathogenesis of
      hypertension. Autoimmune mechanisms are discussed on the basis of common epitopes
      shared between heart and arterial tissue.

PMID- 8554740
TI  - An enzyme array for sialylated N-glycans.

PMID- 8554741
TI  - Violence in the health care environment.
AB  - The rapid rise in the incidence of violence in our society is an increasing risk
      to all Americans. As violence increases for our patients and in society around
      us, it becomes an ever greater problem for all health care personnel. The number
      of threats and violent acts against health care providers has been steadily
      increasing in recent years. The most effective method of managing violence is to
      prevent it. A critical step in prevention is in differentiating between an angry
      individual and a potentially violent individual based on his or her speech,
      appearance, and behavior. Heightened security and changes in the medical
      environment are additional ways of preventing violence. Management of a violent
      incident includes early recognition, de-escalation techniques, and a
      collaborative effort with security personnel.

PMID- 8554742
TI  - One hundred consecutive deep plane face-lifts.
AB  - A subplaytysmal face-lift technique in a deeper anatomical plane of the face was
      described in the 1970s. The deep plane rhytidectomy is based on sound anatomical
      principles of tissue mobilization, advancement, and repair. Wide undermining is
      accomplished in a subplaytysmal plane and continued, extending over the zygomatic
      muscle to the melolabial fold. This large compound cheek flap of skin, muscle,
      and fat is then advanced and tightened to dramatically influence the jowl and
      melolabial fold. A prospective study was undertaken to evaluate the results of
      100 deep plane face-lifts using this technique. Postoperative observations and
      evaluations were made at 1 week, 1 month, and 6 months. A questionnaire response
      and photographic analysis were obtained after 6 months. The rate of hematomas was
      low, with none occurring beneath the thick cheek flap. There were no persistent
      problems, facial irregularities, paralysis, or paresis. Ninety-seven percent of
      the patients were pleased with the aesthetic results. In conjunction with wide
      cervical undermining and an anterior platysmal plication, the deep plane face
      lift affords a predictable improvement for the aging face and neck.

PMID- 8554743
TI  - Vascular anatomy of the nose and the external rhinoplasty approach.
AB  - OBJECTIVE: To characterize the venous, lymphatic, and arterial blood supply of
      the nose and determine the effect of the external rhinoplasty approach on this
      vasculature. We hypothesized that dissection in the areolar tissue plane below
      the musculoaponeurotic layer of the nose will preserve the nasal vasculature and
      minimize postoperative nasal tip edema. DESIGN: The study included preoperative
      and postoperative clinical evaluation, cadaver dissection, and histologic
      examination. In the clinical section, lymphoscintigraphy was performed before and
      after rhinoplasty using the endonasal (transnostril) or external (open) approach.
      Additionally, nasal tip edema was subjectively quantified at specified interval
      after surgery. In the cadaver dissection section, 15 fresh cadavers were
      dissected to identify the venous and arterial vasculature. In the histology
      section, fresh nasal tissue was examined by light microscopy to verify the
      anatomy of arteries, veins, and lymphatic vessels. SETTING: Subjects for the
      clinical section of the study were volunteers undergoing primary rhinoplasty
      surgery at the University of Illinois College of Medicine at Chicago. PATIENTS:
      Lymphoscintigraphy was performed on nine patients who underwent rhinoplasty
      surgery. Seven of these patients underwent postoperative lymphoscintigraphy.
      INTERVENTIONS: The rhinoplasty procedures included three different methods of
      exposure of the nasal structures. Two patients underwent an endonasal
      (transnostril) nondelivery approach using a transcartilaginous incision. Five
      patients underwent the external approach with three receiving dissection in the
      areolar tissue plane below the musculoaponeurotic layer (preserving major nasal
      vasculature) and two undergoing dissection above the musculoaponeurotic layer
      (disrupting nasal vasculature). MAIN OUTCOME MEASURES: In the clinical section of
      the study, the outcome measures were tracer flow as seen on lymphoscintigraphy
      and tip edema scores subjectively quantitated on a scale from 1 (none) to 4
      (maximal). RESULTS: Clinical Section: Lymphoscintigraphy revealed flow of tracer
      along the lateral aspect of the nose (cephalic to lateral crura) to the
      preparotid lymph nodes. Postoperative scans revealed preservation of flow of
      tracer with the endonasal (transnostril) approach and the external approach with
      submusculoaponeurotic areolar tissue plane dissection. There was loss of normal
      flow of tracer with the external approach using dissection that disrupted the
      musculoaponeurotic layer with supratip debulking. The nasal tip edema scores for
      the transnostril and external approach using areolar plane dissection were
      significantly lower than the external approach with disruption of the
      musculoaponeurotic layer. Cadaver Dissection Section: Other than the lateral
      nasal veins, the major arteries, veins, and lymphatic vessels ran superficial to
      the musculoaponeurotic layer of the nose. The lateral and dorsal nasal and the
      columellar arteries comprise an alar arcade that provides the major blood supply
      to the flap elevated in the external rhinoplasty approach. Histologic Section:
      Light microscopy of plastic resin sections verified the lymphoscintigraphic and
      cadaver dissection findings. The lymphatic vessels were located primarily in the
      reticular dermis above the muscle layer. CONCLUSIONS: The major arterial, venous,
      and lymphatic vasculature courses in or above the musculoaponeurotic layer of the
      nose. In the external rhinoplasty approach, dissection in the areolar tissue
      plane below the musculoaponeurotic layer will minimize tip edema and protect
      against skin necrosis by preserving the major vascular supply to the nasal tip.

PMID- 8554744
TI  - Nasal reconstruction using an osteoconductive collagen gel matrix.
AB  - BACKGROUND: Congenital malformations, granulomatous diseases, and trauma can all
      cause destruction of the nasal structural framework, resulting in functional
      nasal obstruction and altered facial cosmesis. Current methods of nasal
      reconstruction include cartilaginous and bony grafts, Silastic implants, and
      homograft only materials. However, these techniques have significant functional
      and cosmetic drawbacks and are not risk free. Native, isotonic, neutral-pH, space
      filling type I collagen gels have been shown to mediate total repair of critical
      size collagen grafts provide a framework for rapid intramembranous ossification
      and osteoconduction of bone from the perimeter of a defect, resulting in total
      bony coverage. OBJECTIVE: To evaluate a novel approach to nasal reconstruction
      using a major defect of the bony nasal dorsum with a type I collagen gel matrix.
      DESIGN: Sixteen retired male breeder Sprague-Dawley rats were divided into
      control and experimental groups. The nasal bones were exposed through a dorsal
      incision and completely removed with a bone-cutting drill to the level of the
      mucosal membranes of the nasal vestibule. Defects in the experimental animals
      were then implanted with 200 micrograms of type I collagen gel, with control
      animals receiving no inlay. After 6 weeks, the animals were examined with three
      dimensional computed tomography before necropsy, at which time the defects were
      photographed, measured by planimetry, and sectioned for histologic analysis.
      RESULTS: Experimental defects were observed to manifest 100% surface area healing
      with a thin layer of bone using a type I collagen gel osteoconductive implant for
      nasal reconstruction. Conversely, control animals showed only a 5.7% (+/- 3.7%
      SD) healing by area. Histologic sections of the collagen gel implant revealed
      restoration of the anatomy with a thin plate of immature bone spanning the defect
      in continuity with the cartilage of the nasal septum and with apparent
      preservation of maxillonasalis suture lines. CONCLUSIONS: Native, isotonic,
      neutral-pH, space-filling collagen gels positively influenced the repair of large
      nasal defects, which showed minimal bone closure in untreated animals. Their use
      in this role merits further investigation.

PMID- 8554745
TI  - The long-term effects of open cosmetic septorhinoplasty on nasal air flow.
AB  - OBJECTIVE: To determine if elective cosmetic septorhinoplasty impacts on nasal
      air flow resistance over the long-term. DESIGN: Case series. Mean postoperative
      follow-up period was 41.5 months (range, 16 to 77 months). PATIENTS: A
      consecutive sample of 200 patients having undergone cosmetic open
      septorhinoplasty by one of us (P.A.A.) before July 1992 were contacted by
      telephone; 50 agreed to participate, and 27 actually participated in the study.
      INTERVENTIONS: Open cosmetic septorhinoplasty performed by one of us (P.A.A.).
      MAIN OUTCOME MEASURES: Comparison of preoperative and postoperative nasal
      resistance values by headout body displacement plethysmography; correlation of
      preoperative and postoperative nasal valve anatomy with nasal resistance values;
      and correlation of postoperative nasal resistance values with subjective
      evaluation of nasal air flow as reported on a 10-point analogue scale. RESULTS:
      Of the 27 patients, 10 had normal preoperative nasal resistance values and 17 had
      elevated resistance values. Preoperative Normal Group: Four of the 10 patients'
      mean resistance values exceeded normal limits postoperatively. One of these four
      patients reported subjective nasal obstruction. Preoperative Abnormal Group: Of
      the 17 patients, surgery resulted in normal resistance values postoperatively in
      six, decreased but still above normal resistance values in eight, and no decrease
      in postoperative resistance values in three. CONCLUSIONS: (1) Patients with
      normal nasal resistance values may suffer long-term, asymptomatic increase in
      nasal resistance values after cosmetic open septorhinoplasty, often with no
      quantifiable change at the nasal valve. (2) Patients with elevated nasal
      resistance measurements generally improve with open septorhinoplasty. Patients
      with isolated septal deformities improve with septoplasty. Patients with upper
      lateral cartilage collapse improve with spreader grafts. The lasting objective
      improvement on the nasal valve using spreader grafts is reported herein for the
      first time. (3) Subjective estimations of nasal patency do not correlate well
      with objective measures of patency, namely nasal resistance measurements. (4)
      Cosmetic septorhinoplasty can alter nasal patency. Continued care must be
      exercised when manipulating the nasal framework for cosmetic purposes, as slight
      changes to the nasal valve may result in significant alterations in nasal air
      flow resistance.

PMID- 8554746
TI  - Implant-retained prosthetic rehabilitation of orbital defects.
AB  - OBJECTIVE: To evaluate the use of endosseous transcutaneous implants to retain
      removable facial prostheses for the rehabilitation of orbital defects. SETTING:
      Tertiary referral center. PATIENTS: Six patients with a history of facial defects
      secondary to orbital exenteration for cancer ablation. OUTCOME MEASURES:
      Clinically noted functional and cosmetic results, patient reports of
      satisfaction, and complications encountered. RESULTS: Twenty-three of 25 implants
      were integrated (postoperative period, 13 to 65 months; mean, 44.2 months),
      representing an integration success rate of 92%. All patients were successfully
      wearing implant-retained prostheses after 48.3 months (post-prosthesis delivery
      period, 1 to 48.3 months; mean, 24.5 months). Overall patient satisfaction was
      very high. CONCLUSIONS: Implant-retained prosthetics represent a safe and
      effective treatment option. It is anticipated that this treatment will become the
      standard of rehabilitative care for patients with orbital defects.

PMID- 8554747
TI  - The management of ectropion using the tarsoconjunctival composite graft.
AB  - OBJECTIVE: To demonstrate the technique, advantages, and results of autogenous
      tarsal grafts in the treatment of ectropion with lower eyelid retraction. DESIGN:
      Fourteen patients treated with autogenous tarsal grafts were evaluated. Follow-up
      ranged from 6 to 30 months (mean follow-up, 10 months). SETTING: All patients
      were treated at the University of Kansas Medical Center, Kansas City, December
      1990 through June 1993. PATIENTS: Of 14 patients with ectropion who were treated
      with this technique, nine had facial nerve paralysis, three had had previous
      periorbital trauma resulting in cicatricial ectropion, one patient had orbital
      and congenital lower lid fibrosis, and one patient had Graves' ophthalmopathy
      with lower lid retraction. INTERVENTION: All patients underwent autogenous tarsal
      grafting. Eleven patients also underwent combined laterocanthal suspension
      (tarsal tongue technique). Seven patients underwent associated upper lid gold
      weight loading. One patient underwent a medial canthopexy. RESULTS: All patients
      had marked improvement functionally and cosmetically. One patient had slight
      under-correction. Results have remained stable for over 2 years. CONCLUSIONS:
      Autogenous tarsal grafts aid in the long-term stability of lower lid ectropion
      repair. Autogenous tarsal grafting has distinct advantages over other described
      techniques. When treating paralytic ectropion, other rehabilitative techniques
      must be additionally employed.

PMID- 8554748
TI  - Healing by secondary intention of auricular defects after Mohs surgery.
AB  - OBJECTIVE: To evaluate secondary intention healing of full-thickness skin defects
      of the auricle. Immediate reconstruction of full-thickness skin defects after
      cancer surgery is an accepted surgical method used to preserve function and to
      minimize cosmetic deformity. However, healing by secondary intention offers the
      advantages of optimal cancer surveillance, simplified wound management, and
      avoidance of reconstructive procedures with their associated costs and potential
      complications. Accurate prediction of the course of wound healing would allow a
      rational approach to selection of patients for surgical or nonsurgical repair.
      DESIGN: We observed 133 patients with full-thickness auricular defects (helix,
      antihelix, concha, pretragal and tragal area, lobule, and posterior aspect) after
      Mohs surgery and documented a variety of parameters affecting wound healing,
      including the location, depth, and size of the wound and use of antibiotics.
      Patients were examined at intervals and determination was made regarding cosmesis
      at least 6 months after surgery. RESULTS: All wounds healed by secondary
      intention within 10 weeks. Analgesics were generally not required. Antibiotics
      were arbitrarily used in 13% of the patients. Three infections occurred with no
      permanent disfigurement. CONCLUSIONS: The location of the wound in the auricular
      subunit is predictive of the cosmetic result. Exposed cartilage is not a
      contraindication for secondary intention healing. Prophylactic antibiotics are
      not routinely required when exposed cartilage is present. The results of
      secondary intention healing are often more cosmetically pleasing than those of
      surgical repair.

PMID- 8554749
TI  - The accurate diagnosis of oral lesions in human immunodeficiency virus infection.
      Impact on medical staging.
AB  - OBJECTIVE: To compare identification of oral candidiasis (OC) and oral hairy
      leukoplakia (OHL) by medical examiners and oral/dental examiners and to assess
      the impact of these diagnoses on the medical staging of the human
      immunodeficiency virus (HIV). DESIGN: Retrospective analysis of data collected by
      medical and oral/dental examiners at the baseline examination of a prospective
      study. SETTING: Homosexual men and men and women who were parenteral drug users
      residing in New York City, enrolled in a longitudinal cohort study. SUBJECTS: A
      total of 245 individuals participated in this study. MAIN OUTCOME MEASURES: The
      diagnoses of OC and OHL as recorded in the medical and oral/dental charts were
      analyzed retrospectively for the same medical and oral/dental evaluation visits.
      The medical staging of HIV infection based on that evaluation was analyzed
      concomitantly. RESULTS: Among homosexual men, the oral/dental examiners diagnosed
      OC in 11% of the individuals and the medical examiners in 4%. In the same cohort,
      OHL was diagnosed by the oral/dental examiners in 14% of the individuals and by
      the medical examiners in 8%. Among the parenteral drug users the oral/dental
      examiners diagnosed OC in 29% of the individuals while the medical examiners made
      this diagnosis in 11%. In the same cohort, OHL was diagnosed by the oral/dental
      examiners in 9% of the individuals and by the medical examiners in 2%. The OC and
      OHL diagnoses affected the medical staging of 12% of the HIV-positive homosexual
      men and of 22% of the HIV-positive parenteral drug users. Forty percent of the
      HIV-positive homosexual men and 79% of the HIV-positive parenteral drug users
      with stage-defining oral lesions were not properly identified by the medical
      examiners. CONCLUSIONS: Specific training and a comprehensive oral examination
      have a significant impact on the diagnoses of OC and OHL, and on the medical
      staging of individuals with HIV infection.

PMID- 8554750
TI  - Prognostic factors in T3,N0-1 glottic and transglottic carcinoma. A
      multifactorial study of 221 cases treated by surgery or radiotherapy.
AB  - OBJECTIVE: To evaluate prognostic factors in patients with T3,N0-1 glottic and
      transglottic carcinoma treated in a single institution. DESIGN: Retrospective,
      nonrandomized case series. SETTING: Tertiary case referral centers, ambulatory or
      hospitalized care. PATIENTS: Two hundred twenty-one consecutive cases of stage
      III glottic or transglottic squamous cell carcinoma. Tumor stage was T3,N0,M0 in
      167 cases and T3,N1,M0 in 54 cases. INTERVENTIONS: Surgery in 176 cases and
      radiotherapy in 45 cases. MAIN OUTCOME MEASURES: Recurrences and survival
      (multivariate). RESULTS: Almost 7% of the patients who underwent surgery and
      39.6% who had radiotherapy had local recurrences. Recurrences in the neck were
      seen in 16.4% of the patients who underwent surgery and in 10.5% of those who had
      radiotherapy. Distant metastases were diagnosed only in patients who underwent
      surgery (4.6%). The 5-year actuarial overall survival rates were 56.3% in the
      surgical group and 35.2% in the radiotherapy group (P = .007). Age involvement of
      pyriform sinus, N stage, and history of tracheostomy were independent prognostic
      factors for risk of death. CONCLUSIONS: The presence of metastatic lymph nodes,
      age, and involvement of the pyriform sinus were the important prognostic factors
      in patients who underwent surgery. A small group of patients with T3,N0,M0 tumors
      could benefit from radiotherapy, with surgery reserved for recurrence.

PMID- 8554751
TI  - Delayed toxic shock syndrome after functional endonasal sinus surgery.
AB  - Toxic shock syndrome (TSS) is an uncommon, severe, multisystem illness that may
      follow any surgical procedure. It usually occurs in the immediate postoperative
      period and is manifested by the sudden onset of a high fever and a variety of
      other signs and symptoms. The reported incidence of TSS after nasal surgery is 16
      cases per 100,000 patients. We report five unusual cases of delayed TSS that
      occurred after functional endonasal sinus surgery in which no packing was used.
      Toxic shock syndrome developed in three children and two adults 5 days to 5 weeks
      postoperatively. All patients were treated successfully with no sequelae. The
      pathophysiologic features, clinical manifestations, and treatment of TSS are
      described in detail.

PMID- 8554752
TI  - Imaging quiz case 1 and 2. Odontogenic keratocyst (OK) of the mandible.

PMID- 8554753
TI  - Maintaining quality in a discount store arena.

PMID- 8554754
TI  - [The cultural policy of the Journal of Biological Research].

PMID- 8554755
TI  - [New forefronts in cardiovascular physiology: a visible contribution to
      medicine?].

PMID- 8554756
TI  - [The future of research in Italy].

PMID- 8554757
TI  - [In memory of Prof. Mario Decandia].

PMID- 8554758
TI  - [Address of the outgoing President to the LXIV General Assembly of the Italian
      Society of Experimental Biology].

PMID- 8554759
TI  - Evaluation of Oxyrase enrichment method for isolation of Campylobacter jejuni
      from inoculated foods.
AB  - Recovery limits were evaluated for Campylobacter jejuni in an existing Food and
      Drug Administration (FDA) enrichment broth (EB) formula supplemented with Oxyrase
      enzyme. Cultures of Camp. jejuni were inoculated into EB or EB containing 10% raw
      milk, raw oysters, crabmeat or mushrooms. After 24 and 48 h of enrichment, Camp.
      jejuni was isolated on four selective agars. No significant differences in
      recovery rates for Camp. jejuni were observed in the Oxyrase enrichment under
      normal atmosphere or in the existing FDA method under modified atmosphere.
      Increase of enrichment time from 24 to 48 h did not improve the recovery rates.
      However, the Oxyrase enrichment was cost effective, less time consuming, and
      simpler to perform than the established method.

PMID- 8554761
TI  - Fate of Aeromonas and Yersinia on modified-atmosphere-packaged (MAP) cod and
      trout.
AB  - The growth/survival of Aeromonas spp. and Yersinia enterocolitica on cod and
      trout stored in two modified atmospheres at 0 degrees, 5 degrees and 12 degrees C
      was compared with that on aerobically stored fish. Both organisms grew on
      aerobically stored fish at all three temperatures. Growth on the modified
      atmosphere-stored fish was never greater and was generally markedly less than on
      aerobically stored fish. This reduction in growth was greater in the higher
      carbon dioxide-containing atmosphere and at the lower temperature(s).

PMID- 8554762
TI  - Tolerance to acid in pH 5.0-grown organisms of potentially pathogenic gram
      negative bacteria.
AB  - A wide range of potentially pathogenic species of Gram-negative bacteria were far
      more resistant to extreme acidity (pH 2.0-3.5) when cultured at pH 5.0
      (habituated to acid) than after pH 7.0 culture. The differences were particularly
      great for Citrobacter spp., Enterobacter spp., Klebsiella spp. and for Vibrio
      parahaemolyticus; substantial habituation was also observed for Proteus mirabilis
      and Aeromonas formicans but the effect was less marked for Serratia marcescens
      and Acinetobacter calcoaceticus. Growth at pH 5.0 was substantially poorer than
      at pH 7.0 for most of the above species and also for Salmonella typhimurium and
      Salm. enteritidis but phosphate markedly enhanced growth at pH 5.0 for many of
      these species without affecting growth at pH 7.0.

PMID- 8554760
TI  - Aggregation-promoting factor in pig intestinal Lactobacillus strains.
AB  - Autoaggregation was frequently encountered among intestinal lactobacilli isolated
      from weaned pigs. The aggregation mechanism was shown to be mediated by the
      production of a proteinaceous aggregation-promoting factor in two strains of
      Lactobacillus reuteri. A 32 kDa aggregation-promoting protein was detected in
      these strains by cross-reaction with rabbit polyclonal antibodies for Aggregation
      Promoting Factor produced by the human isolate Lact. plantarum 4B2. Coaggregation
      reactions of Lact. reuteri strains with pathogenic and non-pathogenic Escherichia
      coli were detected.

PMID- 8554763
TI  - The recovery of heat-stressed Escherichia coli in lake water microcosms.
AB  - Escherichia coli was heat stressed at 55 degrees, 60 degrees or 65 degrees C in
      sterile flasks of lake water. After 6 h at these temperatures the viable count on
      nutrient agar had dropped below the limits of detection (1 colony in 100 ml). The
      flasks were transferred to a 15 degrees C incubator and left for 7 d. Recovery of
      the stressed E. coli was shown to occur within 48 h at this temperature. Recovery
      also occurred in microcosms amended with 5% (v/v) synthetic sewage. The stressed
      E. coli multiplied in the amended but not in the unamended microcosms.

PMID- 8554764
TI  - Development of RAPD protocol for typing of strains of lactic acid bacteria and
      enterococci.
AB  - A protocol for typing strains of lactic acid bacteria and enterococci based on
      randomly amplified polymorphic DNA (RAPD) fragments has been developed. Using a
      single 10-mer primer, fingerprints were achieved without the need to isolate
      genomic DNA. Different conditions of DNA release and amplification were
      investigated in order to obtain reproducible results and high discrimination
      among strains. This RAPD protocol was successfully applied for the typing of
      strains belonging to the species Lactobacillus acidophilus, Lact. helveticus,
      Lact. casei, Lact. reuteri, Lact. plantarum, Enterococcus faecalis, Ent. faecium
      and Streptococcus thermophilus.

PMID- 8554765
TI  - Cloning and nucleotide sequence of the gene for acidocin 8912, a bacteriocin from
      Lactobacillus acidophilus TK8912.
AB  - Acidocin 8912 is a bacteriocin produced by Lactobacillus acidophilus TK8912. The
      acidocin 8912 structural gene, acdT, was cloned and determined. It was located on
      the 14-kb plasmid pL103 and encoded a 46 amino acid precursor including a 20
      amino acid N-terminal extension. The precursor sequence of the acdT gene shows a
      conservation of the general structural characteristics of the bacteriocin
      precursors from some lactic acid bacteria.

PMID- 8554766
TI  - Impedance as an alternative to MPN enumeration of coliforms in pasteurized milks.
AB  - Samples (900) of pasteurized whole, semi-skimmed and skimmed milk were subjected
      to conventional enumeration of coliforms by a nine-tube most probable number
      (MPN) technique, and impedance enumeration, in parallel. Regression analysis of
      the positive samples (98) showed that impedance enumeration was at least as
      accurate as the MPN method but results were obtained faster, with all testing
      being completed in 20 h, rather than 48 h. Consumable requirements, and staffing
      levels, were also much less with the impedance system. The impedance method could
      therefore beneficially replace the conventional method.

PMID- 8554767
TI  - Ascorbate as an induction inhibitor of beta-lactamase in a strain of Enterobacter
      cloacae.
AB  - The effect of ascorbate and anaerobiosis of beta-lactamase content (constitutive
      and inducible) in relation to the susceptibility of a standard strain of
      Enterobacter cloacae to ampicillin was studied. Enterobacter cloacae ATCC 13047
      showed increasing susceptibility to ampicillin when incubated anaerobically in
      the presence of increasing concentrations of ascorbic acid. The inducible beta
      lactamase activity in the cell-free extracts of Ent. cloacae decreased when the
      bacterium was grown aerobically in the presence of ascorbic acid. Under anaerobic
      growth conditions, however, ascorbic acid abrogated the induction of the enzyme
      completely. On the other hand, the constitutive enzymatic activity was markedly
      decreased as the bacterium was grown anaerobically. Thus under these growth
      conditions ascorbate-anaerobiosis, the total beta-lactamase level in the presence
      of ampicillin as inducer fell below the basal constitutive activity observed in
      the absence of ampicillin.

PMID- 8554769
TI  - Comparison of conventional culture and three rapid methods for the detection of
      Salmonella in poultry feeds and environmental samples.

PMID- 8554768
TI  - Variability of the 5'-end of the large subunit rDNA and presence of a new short
      class of rRNA in Rhizobiaceae.
AB  - A highly variable region of DNA was found between positions 115 and 388
      (Escherichia coli numeration) of the large subunit (ls) rRNA genes of 55
      rhizobial and agrobacterial strains. In each case this heterogeneity was
      accompanied by the presence of a new rRNA species approximately 130 bp long. This
      novel rRNA species corresponded to the 5'-end of the ls rRNA genes. An additional
      rRNA processing site was located in the central region of the remaining ls rRNA
      of many of the Rhizobium leguminosarum and Rh. etli strains, and in all of the
      agrobacteria studied, excepting the type strain of Agrobacterium vitis NCPPB 3554
      and Agrobacterium sp. strain ChAg4.

PMID- 8554770
TI  - Acquisition of the novel name-nameless category (N3C) principle by young children
      who have Down syndrome.
AB  - Acquisition of the novel name-nameless category (N3C) principle by 22 children
      with Down syndrome between the ages of 2.42 and 3.33 years was examined to
      investigate the generalizability of a new approach to early lexical development:
      the developmental lexical principles framework. Results indicated that, as
      predicted, the N3C principle (operationally defined as the ability to fast map a
      new word to a [basic level] category), is not available at the start of lexical
      acquisition. The predicted link between ability to use the N3C principle and
      ability to perform exhaustive categorization of objects was supported. Children
      who used the principle had significantly larger productive vocabularies than did
      those who did not and, according to maternal report, had begun to acquire new
      words rapidly.

PMID- 8554771
TI  - Social information processing by aggressive and nonaggressive men with mental
      retardation.
AB  - The social information-processing skills of 16 aggressive and 19 nonaggressive
      men with borderline to moderate mental retardation were examined in light of some
      of the steps described in Dodge's social information-processing model (Dodge,
      Pettit, McClaskey, & Brown, 1986). Contrary to expectations based on Dodge et
      al.'s findings with children who did not have mental retardation, aggressive and
      nonaggressive groups did not differ in their ability to generate multiple
      solutions or in their ability to provide appropriate responses. Similar to Dodge
      et al.'s findings, however, subjects in the aggressive group generated
      significantly more aggressive solutions and tended more often to give an
      aggressive response first than did the nonaggressive subjects. Preliminary
      implication for treatment were offered.

PMID- 8554772
TI  - Use of computer- and teacher-delivered prompts in discrimination training with
      individuals who have mental retardation.
AB  - Individuals with mental retardation received training on a series of 16 visual
      discrimination problems. Eleven subjects received computer-delivered instruction
      with a stimulus-fading procedure and 11 were trained with verbal and nonverbal
      prompts delivered by a human teacher. We found that (a) the teacher's prompts
      were effective with more subjects than was the computer-based fading procedure;
      (b) transfer to stimulus control to task stimuli was poor with the teacher's
      prompts but nearly perfect when fading was effective; and (c) subjects learned
      more discrimination problems with the computer-delivered fading procedure. These
      results suggest that the computer could be a useful tool to assist in
      discrimination training in special-education settings.

PMID- 8554773
TI  - Aging in adults with Down syndrome: report from a longitudinal study.
AB  - Changes in functioning related to aging were examined in 34 adults (14 females,
      20 males) with Down syndrome who were 22 to 56 years of age. Changes in
      functioning over 3 to 4 years were examined, with age, IQ at entry into the
      study, and gender considered. Neither effects of age at entry nor change over
      time were significant, suggesting that changes related to aging in adults with
      Down syndrome were minimal. In contrast, IQ at entry had a significant effect on
      all performances, suggesting that any examination of aging must consider
      intellectual level. Results do not support the idea that adults with Down
      syndrome show rapid age-related declines in functioning apart from the occurrence
      of a progressive dementia such as Alzheimer's disease.

PMID- 8554774
TI  - Auditory and visual evoked potentials in individuals with organic and cultural
      familial mental retardation.
AB  - Brainstem, middle-latency, and long-latency auditory evoked potentials (BAEPs,
      MAEPs, and LAEPs) and visual evoked potentials (VEPs) were recorded from subjects
      without mental retardation (control subjects) and from subjects with organic
      mental retardation or cultural-familial mental retardation. Both mentally
      retarded groups had smaller mean VEP amplitudes and longer mean LAEP latencies in
      response to target stimuli than did the control subjects, showing that the target
      stimuli were evaluated more slowly by the subjects with than by those without
      mental retardation. We found no significant differences between the mentally
      retarded and control groups with regard to BAEPs or MAEPs, and the two mentally
      retarded groups did not differ significantly in any EP parameter. The
      implications of these results for the defect and developmental theories of mental
      retardation were discussed.

PMID- 8554775
TI  - The Aberrant Behavior Checklist-Community: factor validity and effect of subject
      variables for adults in group homes.
AB  - The factor validity of the new Aberrant Behavior Checklist-Community (ABC-C) was
      determined with 1,040 group home residents. Exploratory factor analysis indicated
      that the factor structure derived from the original ABC appears to be valid for
      the ABC-C when used with this population. Coefficients of congruence showed a
      high level of concordance with the original factor structure, and internal
      consistency continued to be high for each of the five subscales. Analyses for the
      effects of age, gender, and level of mental retardation indicated that some
      correction is appropriate for each of these variables when scoring the ABC-C.
      Further analyses explored the effects of subjects variables such as visual and
      auditory handicaps and the presence of epilepsy or Down syndrome. Psychotropic
      medication use was often associated with subscale score differences. The original
      ABC factor structure appears valid for scoring the ABC-C with community-based
      adults, at least those living in group homes.

PMID- 8554776
TI  - Diagnostic overshadowing and mental retardation: a meta-analysis.
AB  - Clinicians who minimize the significance of emotional disorders in persons with
      mental retardation may be displaying the diagnostic overshadowing judgmental
      bias. A meta-analysis of the existing literature on this bias was conducted to
      determine its reliability, the size of its effect, and its potential clinical
      significance. Results show the effect to be reliable across studies; the size of
      the effect was small to moderate. Interpretation of the clinical significance of
      these results is clouded by the absence of in vivo studies. Additional concerns
      include insufficient attention given to clinician and situational variables
      moderating the presence of diagnostic overshadowing.

PMID- 8554778
TI  - Emergent stimulus-response relations in children with severe mental retardation.

PMID- 8554777
TI  - Clomipramine treatment for stereotype and related repetitive movement disorders
      associated with mental retardation.
AB  - The efficacy of the serotonin uptake inhibitor clomipramine in the treatment of
      stereotyped and related repetitive behavior disorders was tested in individuals
      with severe and profound mental retardation. A double-blind, placebo-controlled
      crossover trial of clomipramine was associated with significant reductions in the
      frequency and intensity of stereotyped behavior and teacher ratings of
      stereotypy, hyperactivity, and irritability as well as increased adaptive
      engagement and decreased staff intervention for nontargeted behavior problems.
      Adverse effects occurred in 3 of the 10 subjects. Of the 7 subjects who tolerated
      the drug, 6 exhibited a clinically significant improvement in one or more
      repetitive behaviors. Our results provide support for the hypothesis that
      clomipramine is effective in treating stereotyped and related behaviors
      associated with mental retardation.

PMID- 8554779
TI  - Behavioral treatment of Rett's disorder: ineffectiveness in three cases.

PMID- 8554780
TI  - [Temporal threshold for middle cerebral artery infarction].
AB  - We describe a rat model for middle cerebral artery occlusion and discuss its
      usefulness for the study of structural consequences of various ischemic periods.
      We inserted 4/0 polyethylene sutures into the external carotid artery of 48
      Wistar rats. The tips were rounded and coated with a thin layer of dental
      silicone. By inserting a section 18 mm long we assured that placement of the tip
      was between the origins of the middle and anterior cerebral arteries. The suture
      was withdrawn at predetermined times to allow complete reflux through the common
      carotid. The animals were sacrificed 24 hours after this procedure and tested for
      the presence of infarct by staining with 2,3,5 triphenyl-tetrazolium on 2 mm
      coronal cuts. We identified several differences regarding areas of infarction
      after the different occlusion periods, as shown by ANOVA and Newman-Keuls
      testing. Thus, occlusion for 15 minutes did not provoke infarction; occlusion of
      30, 45 and 60 minutes produced selective infarction of the caudate nucleus and
      putamen; and finally, incomplete cortical infarction appeared after 90 minutes
      and was complete after 2 hours, at which time infarction was similar to that seen
      after 24 hours of occlusion. Intravascular occlusion is a reliable method for
      inducing focal cerebral ischemia, enabling us to confirm the existence of an
      infarction time threshold that is longer for the cortex than for the caudate
      nucleus and putamen.

PMID- 8554781
TI  - [Adult onset mitochondrial myopathy without ophthalmoplegia. Four cases
      attributable to complex III and IV deficits in the respiratory chain].
AB  - Four adults with proximal myopathy of mitochondrial origin but no ocular
      involvement are presented. Biochemical analysis showed combined complex III and
      IV deficits in the respiratory chain in all cases, suggesting an apparent
      correlation between clinical phenotype and biochemical findings. Mitochondrial
      DNA analysis of muscle from 1 patient failed to detect either large-scale
      deletion or point mutations at position 3243 of tRNA(Leu(UUR)) or at 8344 of
      tRNA(Lys). The tissue specificity of the disease and the absence of family
      history suggest that a mutation in a nuclear DNA gene encoding a specific subunit
      of muscle could underlie this disease.

PMID- 8554782
TI  - [The practice of neurology by regional specialists in Vizcaya (Spain)].
AB  - We describe the practice of 3 regional specialists in neurology in 1993 and 1994
      at Hospital de Cruces in Vizcaya. Each neurologist alternately spent 1 day
      working in the hospital ward and another day working in an external clinic in the
      region, thus allowing clinic patients to be seen consistently by the same
      neurologist, while responsibility for inpatients could be shared by 2 physicians.
      All clinic patients in the region and the majority of hospital patients were
      covered by these specialists. A yearly average of 683.05 new patients were seen;
      177.72 (26.01%) as inpatients, 82 (12%) at the hospital-based outpatient clinic
      and 423.33 (61.98%) at other clinics in the region. The wait time for new
      patients in the regional clinics was 119.71 days; 21.97% of these patients were
      classified as having no neurological disease (with diagnoses of syncope and
      peripheral vertigo included in this group), 25.74% had headache and 40.12% had
      cerebrovascular, neuromuscular, degenerative disease or epilepsy. Hospitalized
      patients released with diagnoses of non-neurological disease or cephalea
      represented 12.91% of the total; 50.6% of hospital patients had cerebrovascular
      disease.

PMID- 8554783
TI  - [Apomorphine].

PMID- 8554784
TI  - [Intracranial hypotension and sixth cranial nerve palsy].
AB  - The sixth cranial nerves may be involved in rare cases of post-puncture syndrome
      after lumbar anesthesia as well as in cases of spontaneous intracranial
      hypotension. We present 3 cases of spontaneous intracranial hypotension with
      unilateral or bilateral sixth nerve palsy.

PMID- 8554785
TI  - [Wallenberg syndrome as a sign of rhombencephalitis-meningitis due to Listeria
      monocytogenes].
AB  - We report a case of rhombencephalitis with meningitis in a 36-years-old
      previously healthy man; neurological signs and symptoms were initially consistent
      with a diagnosis of Wallenberg syndrome. Analysis of cerebrospinal fluid showed
      predominantly lymphocytic pleocytosis and elevated protein levels. A CT brain
      scan was normal. MRI of the brain showed a hypertensive type lesion in T2, in the
      right pontomedullary region that suggested inflammation. A blood culture grew
      Listeria monocytogenes. The patient improved and fully recovered with appropriate
      antibiotic treatment. Listeria monocytogenes is a recognized cause of acute
      brainstem meningoencephalitis. Differential diagnoses that must be considered are
      other forms of purulent meningitis, viral meningoencephalitis, granulomatosis
      infections of the central nervous system and, occasionally, stroke.

PMID- 8554786
TI  - [Primary T-cell lymphoma in the central nervous system of immunocompetent
      patients. Clinical and pathological study of two cases].
AB  - Primary T-cell lymphoma in the central nervous system has rarely been described
      in the literature. We report 2 such cases in immunocompetent patients. The first
      presented with subacute encephalopathy affecting both memory and speech. A CT
      scan of the head showed a contrast-enhanced mass around the third ventricle. The
      second presented with 2 partial seizures with secondary generalization; the CT
      scan in this case showed a right temporal lesion. Both underwent surgery for
      total removal of the masses followed by cranial irradiation. Tissue examination
      confirmed the diagnosis. The first patient died 14 months after diagnosis. In the
      second case lymphoma recurred 8 months after surgery.

PMID- 8554787
TI  - [Pontine hematoma: a form of presentation in familial cavernous angiomatosis].

PMID- 8554788
TI  - Aseptic meningitis caused by intravenous immunoglobulin.

PMID- 8554789
TI  - [Striatum-capsular infarction].

PMID- 8554790
TI  - [Dermatomal somatosensory evoked potentials in the diagnosis of focal lesions of
      the spinal cord].
AB  - We studied 13 patients suffering from localized spinal cord lesions by means of
      somatosensory evoked potentials obtained by electrical stimulation at various
      dermatome levels (SEPD). The results were compared to those of somatosensory
      evoked potentials obtained by stimulation of the posterior tibial nerve (SEPpt),
      as well as to clinical and radiologic data. Structural lesions could be
      demonstrated in 8 patients; in 5 patients, however, X-rays were normal and/or
      incompatible with symptoms. We found clear correlations among clinical or
      radiologic data and the level of lesion indicated by SEPD in all 13 patients. In
      one case SEPD were abnormal 6 months in advance of the first alteration in
      magnetic resonance imaging. Abnormal SEPD and SEPpt results were consistent,
      suggesting the existence of a common central pathway to carry stimuli. SEPD
      should be considered a useful, reliable technique for assessing spinal cord
      function, especially when no structural lesion can be demonstrated or when spinal
      injury is doubtful or when several segments are involved.

PMID- 8554791
TI  - [Huntington disease: clinical and genetic study in a Spanish population].
AB  - Clinical and genetic data of 18 unrelated patients diagnosed of Huntington's
      disease were studied. We examined age of onset, form of presentation, years of
      evolution and scores on the Shoulson-Fahn function scale, the Myers disability
      scale and the mini-mental state examination. The 3 clinical parameters show a
      linear correlation with years of disease duration. The mini-mental test was most
      sensitive to progression and was most closely correlated (r = 0.75, p = 0.001).
      Molecular analysis of the IT15 gene for all 18 patients and 96 control chromosome
      was performed; the range of CAG repeats was 9-29 for controls and 36-69 for
      patients. The correlation decreased exponentially with age of onset of symptoms
      and number of CAG repeats.

PMID- 8554792
TI  - [Deletion of 17p11.2 chromosome in Spanish families with hereditary neuropathy
      and abnormal sensitivity to pressure].
AB  - Hereditary neuropathy with abnormal liability to pressure palsies (HNPP) is a
      dominant autosomally transmitted disease that gives rise to foci of peripheral
      nerve myelination, reducing conduction and leading to episodes of palsy and
      sensory changes that are all linked to sensitivity to pressure and traction on
      the affected nerve roots. The molecular basis of HNPP has been identified as a
      submicroscopic deletion of the 17p11.2 chromosome in exactly the same region that
      it is duplicated in Charcot-Marie-Tooth disease, type 1A (CMT1A). We report
      genetic analyses of 13 patients (belonging to 3 families) diagnosed of HNPP by
      means of physical examination and electrophysiologic and morphologic tests (the
      last in 3 cases only). Inter- and intrafamilial variation in symptomatology was
      studied. Some patients presented the usual clinical signs, such as recidivating
      brachial plexus palsy, permanent sensory polyneuropathy, foot deformities and
      others that might also be found in patients with CMT1A. All the patients showed
      electrophysiologic signs of underlying demyelinating polyneuropathy. Genetic
      study centered on detecting the deletion of 17p11.2 by segregation analysis with
      the polymorphic markers VAW409R3a (D17S122) and EW401HE (D17S61). Our results
      confirmed deletion at the CTM1A location of chromosome 17p11.2 in all 13 patients
      examined. These data suggest that the deletion of 17p11.2 plays a causal role in
      HNPP and that it is the most prevalent mutation in this disease; our findings
      constitute new evidence of the importance of the CMT1A/HNPP locus in the
      formation and control of peripheral myelin and in the ultimate functioning of
      peripheral nerves.

PMID- 8554793
TI  - [Neurobrucellosis. A report of 13 cases].
AB  - Thirteen patients with nervous system brucellosis are described. The clinical
      signs were heterogeneous: meningoencephalitis in 5 cases, meningoradiculitis in
      another 5, meningomyelitis with cranial neuropathy in 1 and of a vascular nature
      in 2 others. Neurologic signs appeared during the active phase in 5 patients and
      later in 8. Diagnosis was based on clinical manifestations, serum and
      cerebrospinal fluid (CSF) serology, quantitative changes in CSF and favorable
      response to treatment. Therapy consisted of a combination of 2 or 3 of the
      following drugs: rifampin, doxycycline, streptomycin and trimethoprim
      sulfamethoxazole. In spite of favorable evolution, 5 patients suffered sequelae.
      We suggest that brucellosis be investigated when neurologic deficit ensues with
      no known etiology, especially in endemic countries.

PMID- 8554794
TI  - [Back pain caused by pelvic vascular malformation].

PMID- 8554795
TI  - [Parkinsonism induced by sodium valproate].
AB  - Parkinsonism is a rare side effect of treatment with sodium valproate. We report
      2 elderly women who developed parkinsonian syndrome several years after starting
      valproate therapy, and in whom symptoms disappeared when treatment was withdrawn.
      These cases, along with others in the literature, may support experimental
      evidence for the importance of GABAergic modulation in motor control.

PMID- 8554796
TI  - [Thromboangiitis obliterans with cerebral involvement].
AB  - We report the case of a male with Buerger's disease and neurologic involvement.
      Cerebral arteriography showed multiple distal arterial obliterans with left-sided
      Moya-moya phenomena. Thromboangiitis obliterans is a chronic segmental occlusive
      disease affecting medium-sized and small arteries and veins throughout the body.
      Neurologic signs are rare, occurring in fewer than 2 % of cases, and most often
      found on the cortical surface and adjacent territories. We review the most common
      signs of this entity and its main diagnostic difficulties.

PMID- 8554797
TI  - [Spontaneous remission of cervical epidural hematoma with pathological
      confirmation].
AB  - Spontaneous cervical epidural hematoma (CEH) is a rare entity but one that can
      cause permanent neurologic deficit unless, it is widely believed, surgical
      evacuation is prompt. A diagnosis of CEH is confirmed by computed tomography
      and/or magnetic resonance imaging. Spontaneous remission is unusual, with only 7
      such cases reported in the literature as of 1993. We present a case of CEH with
      clinical remission and confirmation by neuroimaging in a patient who died of an
      unrelated cause. We conclude that when neurologic deficit is incomplete and there
      are no signs of clinical progression after 48 h, surgical treatment should not be
      applied routinely.

PMID- 8554799
TI  - [Treatment of epilepsy among the Guarine (Palenque) tribes].

PMID- 8554798
TI  - [Spontaneous internal carotid artery dissection as a cause of unilateral lower
      cranial nerve palsies].
AB  - We present a 60-year-old man with a complete right IX-XII nerve palsy (Collet
      Sicard syndrome) due to spontaneous right internal carotid artery (ICA)
      dissection. Magnetic resonance imaging (MRI) and MR angiography (MRA) showed
      signs of subadventitial dissection of the right ICA with a mural haematoma that
      expanded the circumference of the vessel at the level of the retrostyloid space,
      adjacent to the IX-XII nerves. No narrowing of the lumen or aneurysms was found.
      Clinical recovery was excellent after treatment with only antiplatelet drugs.
      Cervical internal carotid artery dissection should be included in the
      differential diagnosis of lower cranial nerve palsies. MRI and MRA are
      noninvasive, reliable methods for diagnosis and follow-up, especially in
      subadventitial dissections.

PMID- 8554800
TI  - [Contribution of MRI to the study of the inner ear].
AB  - We analyse the contribution of magnetic resonance (MR) imaging to the study of
      the inner ear for the evaluation of normal anatomy and pathology of the
      membranous labyrinth. Our protocol is discussed with emphasis on 3D SSFP images
      (tridimensional Steady State Free Precession) and high resolution 2D SEF images
      (bidimensional Fast Spin Echo). We comment briefly on the indications of the
      method in neurosensory hearing loss and the way in which it complements CT.

PMID- 8554801
TI  - [Parameters of normalcy in transient otoacoustic emissions].
AB  - The incidence, amplitude and frequency spectrum of transitory otoacoustic
      emissions (TOAE) were analyzed in a sample of 232 normal hearing ears, after
      click stimulation to determine normal parameters. 116 subjects, 58 female ranging
      in age from 18 to 30 years, mean age 23.1 years, and 58 male were from 18 to 32
      years, mean 23.7 years, were included in this study. TOAE were normal in all
      ears, 132 (57%) ears had TOAE at all frequencies between 0.5 and 5 kHz. The mean
      amplitude of TOAE was 16 dB SPL (SD 3.77) and the highest amplitude was elicited
      at 1-2 kHz frequency. The intensity of stimulation correlated directly with
      evoked response amplitude and the subject's age correlated inversely with the
      incidence and amplitude of TOAE.

PMID- 8554802
TI  - [Outpatient surgery in pediatric ENT].
AB  - Adenotonsillectomy is a common surgical procedure. For many patients, outpatient
      adenotonsillectomy is safe and cost-effective. During the 1993-1994 school year,
      365 patients were operated. Complications (1.2%) were minimal and similar to
      those occurring in inpatients (2%) in the same 1992-1993 period. We believe that
      surgery of the tonsils, adenoids and myringotomy can be performed safely as an
      outpatient procedure if the candidates for ambulatory surgery are carefully
      selected by the surgeon.

PMID- 8554803
TI  - [Congenital cholesteatoma of the petrous process and mastoid: a report of two
      cases].
AB  - Congenital cholesteatoma are unusual. They may arise in different sites of the
      temporal bone: petrous process, middle ear and mastoid. Primary cholesteatomas
      originate from embryonary ectodermal inclusions but the pathogenesis is not clear
      and many different hypotheses regarding its origin have been suggested. The
      clinical diagnosis is not easy if the tympanic membrane is normal, and
      computerized tomography and magnetic resonance imaging are useful. We report two
      cases of congenital cholesteatoma: One located in the petrous process and the
      other in the mastoid without affection of the tympanic cavity.

PMID- 8554804
TI  - [New protocol for the early diagnosis of acoustic schwannoma in the outpatient
      clinic].
AB  - For the last two years we have been testing a protocol for early diagnosis of
      acoustic schwannoma. We analyzed the results obtained in outpatients of the ENT
      clinic for ten months. Using the protocol described 10.7% accurate diagnoses,
      were obtained although in only one diagnosis was made in the intracanalicular
      stadium that was susceptible to ENT surgery.

PMID- 8554805
TI  - [Orbital cellulitis and permanent amaurosis: clinical case].
AB  - Orbital cellulitis is a rare, potentially serious but complication of acute
      sinusitis. It is more frequent and benign in children, but in adults usually
      requieres surgical drainage of the affected sinus. We report a case of aggressive
      evolution with permanent blindness in an adult without general or local risk
      factors, in spite of adequate treatment. The literature is reviewed.

PMID- 8554806
TI  - [Wegener's granulomatosis of the nasal fossa].
AB  - A 62-year-old female patient consulted for a suppurative-hemorrhagic nasal
      condition 18 months evolution. Exploration found granulomatous rhinitis which was
      producing septal perforation and histology compatible with necrotizing
      granulomatous vasculitis, fulfilling the diagnostic criteria for focal Wegener's
      granulomatosis, in view of the absence of lung and renal damage. Treatment with
      trimethoprim-sulfamethoxazole alone described in the medical literature as an
      option for this process, yielded excellent results with remission of symptoms and
      normalization of the exploration.

PMID- 8554807
TI  - [Pediatric laryngeal papillomatosis: our experience (three cases)].
AB  - Three cases of juvenile laryngeal papillomatosis were treated at our hospital
      between 1984 and 1994. Papillomas were excised in all patients because of upper
      airway obstruction. Two were given alpha interferon as complementary treatment.
      Two patients are asymptomatic after years of follow-up and one is still taking
      alpha interferon.

PMID- 8554808
TI  - [Mucoepidermoid carcinoma of the larynx. A case report].
AB  - We report a case of laryngeal mucoepidermoid carcinoma that was diagnosed in the
      Hospital Miguel Servet of Zaragoza. The unusual tumor site and difficult
      diagnosis were notable and, above all the fatal outcome after local recurrence
      and metastasis in spite of good overall prognosis.

PMID- 8554809
TI  - [Laryngeal paraganglioma: a case report].
AB  - A case of laryngeal paraganglioma in a 25-year-old female is reported. The site
      of the tumor was the left aryepiglotic fold and ventricular band. The diagnosis
      was made by histology and immunohistochemistry medial thyrotomy was performed in
      order to remove a bilateral carotid paraganglioma. We analyzed 76 cases reported
      in the world literature, clinical, histological, prognostic, and therapeutic
      factors in laryngeal paraglioma.

PMID- 8554810
TI  - [Moderately differentiated neuroendocrine carcinoma of the larynx].
AB  - We present a case of moderately differentiated neuroendocrine carcinoma of the
      larynx. These tumors represent 0.6% of all laryngeal carcinomas. Histological
      diagnosis requires the use of immunohistochemical methods, the tumoral cells
      presenting positivity for epithelial markers (cytokeratin) and neuroendocrine
      markers (chromogranin). Clinically, their location is supraglottic and they
      affect mainly males between the 6th-7th decades of life. The prognosis is better
      than that of squamous carcinoma or adenocarcinoma. The differential diagnosis
      must be made with granular cell tumor and paragangliomas.

PMID- 8554811
TI  - [Localized laryngeal amyloidosis. Treatment with CO2 laser].
AB  - Amyloidosis of the upper airways is rare. The larynx is the most common site of
      involvement. Primary amyloidosis may be localized or generalized. We report a
      case of laryngeal amyloidosis in which amyloid deposits were confined to the
      larynx (right false vocal cord and subglottis) and successfully treated with CO2
      laser.

PMID- 8554812
TI  - [Tracheobronchial foreign body in a laryngectomized patient. An unusual case].
AB  - We report an interesting case of left tracheobronchial foreign body that occurred
      in a laryngectomized patient during and episode. The patient had few symptoms
      because of the location of the foreign body in the tracheobronchial tree.
      Bronchotomy was used to remove the foreign body. The literature was reviewed for
      clinical and therapeutic aspects.

PMID- 8554813
TI  - [Parotid tuberculosis].
AB  - Two rare cases of parotid gland tuberculosis are presented, which confirms the
      rising incidence of tuberculosis in Spain. Preoperative diagnosis is difficult,
      as the disease may be mistaken for a neoplastic process, and complementary tests,
      fine needle aspiration biopsy, CAT, analyses and chest X-rays are frequently
      nonspecific, particularly in the absence of a history of lung tuberculosis. As
      the diagnosis is histopathological, surgery in the form of a parotidectomy with
      preservation of the facial nerve is the treatment of choice, followed by 9 months
      of tuberculostatic medication. Only in cases in which the preoperative evidence
      (antecedents, chest X-rays) suggests the specific origin of the disease may
      antituberculosis treatment be given. Positive patient response is diagnostic.

PMID- 8554814
TI  - [Metastasis of breast carcinoma in parotid. A case report and review of the
      literature].
AB  - Breast cancer is a systemic illness that sometimes affects the ENT area. We
      report a case of parotid tumor with progressive growth, which rarely originals in
      the ENT area. We review the literature and discuss the treatment.

PMID- 8554815
TI  - [Launois Besaude lipomatosis].
AB  - We report two new cases of Launois Bensaude syndrome. Diagnostic and therapeutic
      aspects are discussed.

PMID- 8554816
TI  - [Does branchiogenic carcinoma exist or not?].
AB  - A 43 year-old man with a cystic mass on the side of the neck was admitted to the
      hospital for possible branchial cyst. The histopathological analysis showed a
      carcinoma developed on a branchial cyst. After reviewing the literature, we
      conclude that carcinoma developing on a branchial cyst is uncommon, if, indeed,
      it exists at all. The diagnostic criteria should be adhered to strictly. When
      confronted with this histopathologic diagnosis, the possibility of cystic
      metastasis to the neck of a squamous carcinoma of unknown origin should be
      considered.

PMID- 8554817
TI  - [Partial lower turbunectomy. Indication and technical description].

PMID- 8554818
TI  - [The mucosal subepithelial space in the middle ear in prolonged tubal
      dysfunction].
AB  - Prolonged tubal dysfunction produces changes in the mucosa and subepithelial
      space. We report the results of an experimental study in Mongolian gerbils.

PMID- 8554819
TI  - [Relations between the maxillary sinus and upper maxillary process.
      Anatomotopographic study].
AB  - The anatomic proximity of the antral floor and superior alveolar processes favors
      the propagation of infections from teeth to neighboring structures, as was
      pointed out first by John Hunter. A radiologic and anatomic study was made of
      these anatomic relations and the bony substance between the alveolar ridge and
      maxillary sinus was measured. No firm criteria for normality could be established
      because of the variability of the maxillary sinus. Variations in environmental
      and developmental conditions easily modify its morphology.

PMID- 8554820
TI  - [Inner ear diseases of probable autoimmune origin and its response to steroid
      treatment].
AB  - Cellular and/or humoral immune reactions may be involved in the development of
      some cochleovestibular dysfunctions long considered idiopathic. In a clinical
      study of 98 patients, 82 of them with cochleovestibular disorder, a battery of
      immunologic studies was used. Thirty-one patients received steroid treatment, of
      which 19 obtained good results; 5 of these patients had positive serum
      antibodies.

PMID- 8554821
TI  - [Antibiotic prophylaxis in surgery of uncomplicated cholesteatoma: review of 150
      patients].
AB  - A review was made of 150 cases of chronic otitis media caused by cholesteatoma
      that were operated consecutively; no complications or active otorrhea was
      present. In 61.3% of cases, prophylactic antibiotic (PA) treatment was given on
      the basis of the surgeon's criteria, which probably reflected the presence or
      absence of risk factors. Most patients were given a penicillin or penicillin
      derivative (amoxi-ampicillin followed by cephalosporins). Antibiotic
      administration was prolonged longer than necessary (mean 3.4 days). PA was not
      associated with important complications. Postoperative infection occurred in
      10.7% of cases, usually infection of the surgical wound, most commonly by
      Staphylococcus aureus. Otorrhea occurred in 7.3% of cases in the 15 days after
      surgery and was more frequent in patients treated via an endomeatal approach and
      in those who had ossicular prosthesis. Prophylactic antibiotic treatment produced
      no benefit to our patients in the form of any reduction in number of surgical
      infections, postoperative otorrhea or mean hospital stay. Therefore, PA is not
      recommended in surgery for uncomplicated cholesteatoma. When risk factors are
      present, a suitable and complete antibiotic treatment may be indicated.

PMID- 8554822
TI  - [Hyaluronidase as a therapeutic alternative in perforated tympanum].
AB  - There are many causes of tympanic perforation but usually only one treatment,
      surgical. However, many patients cannot or will not undergo surgery. In such
      cases, treatment with sodium hyaluronidate may be satisfactory. In our group of
      20 patients with 21 tympanic perforations who underwent this treatment, 15
      evolved favorably. The drawbacks and patient selection are discussed.

PMID- 8554823
TI  - [Study of spontaneous cytotoxic activity in laryngeal carcinoma: prognostic
      value].
AB  - The status of natural killer (NK) cell activity in peripheral blood, based on
      number and functional state, was studied in relation to the clinical and
      histopathologic stage of 52 patients with laryngeal carcinoma and in 23 healthy
      controls. The number of NK cells, estimated using CD16 and CD56 monoclonal
      antibodies, was similar in patients and controls and showed no relation to tumor
      size and nodal involvement. NK cell function did not show significant differences
      in spontaneous cytotoxic activity either overall or in relation to tumor size and
      the presence of palpable lymph nodes. However, cytotoxic activity was
      significantly lower in patients who had histologically confirmed nodal
      involvement. NK activity under 36% (the percentage of specific lysis at an
      effector:target dilution of 50:1) was suggested the probable presence of nodal
      metastases and was a highly sensitive and specific test. In patients with
      laryngeal carcinoma, NK-cell cytotoxic activity may be an independent prognostic
      parameter for evaluating cervical lymph node involvement.

PMID- 8554825
TI  - [Metastases to the temporal bone. A report of two cases].
AB  - Two cases of metastasis to temporal bone from primary tumors are reported, one
      from bronchogenic carcinoma and the other from prostate adenocarcinoma.
      Metastasis to temporal bone is rare and the literature is reviewed.

PMID- 8554824
TI  - [Differential diagnosis of neurinomas of the jugular foramen and glomus jugulare:
      a clinical case].
AB  - Neurinomas or schwannomas of the jugular foramen are rare tumors whose
      differentiation from tumors of the jugular body may be difficult because they
      share common symptoms. Since schwannomas at this site are less aggressive than
      tumors of the jugular body and certain elements of their treatment differ, it is
      important to make a correct diagnosis promptly. A well-documented case of
      schwannoma of the jugular foramen is reported and its differential diagnosis is
      discussed in the light of the literature.

PMID- 8554826
TI  - [Actinomycosis of the tonsils with a pseudotumoral presentation: a clinical
      case].
AB  - A case of actinomycosis of the tonsils with a neoplasm-like clinical presentation
      is presented. Tonsillectomy confirmed the diagnosis and the patient's evolution
      was favorable after postoperative antibiotic therapy. The scant literature on
      cervicofacial actinomycosis is reviewed. These processes often are confused with
      neoplasms, as in our case, or with mandibular osteomyelitis. Treatment is surgery
      and prolonged antibiotic administration. Actinomycosis should be considered in
      the differential diagnosis of cervicofacial masses, particularly when the biopsy
      is negative for carcinoma.

PMID- 8554827
TI  - [Wegener's granulomatosis: a diagnostic review and case report].
AB  - Wegener's granulomatosis (WG) is characterized by necrotizing granulomas and
      vasculitis that may affect any organ. The upper and lower respiratory tract and
      kidney usually are affected. WG is diagnosed by determination of anti-neutrophil
      cytoplasm antibody (ANCA), a highly sensitive and specific test that is
      particularly important in the early stages to achieve the best prognosis. We
      describe a case in a 28-year-old man that exemplifies some of the diagnostic
      features of WG.

PMID- 8554828
TI  - [Laryngeal histoplasmosis].
AB  - A case of laryngeal histoplasmosis is reported. This laryngeal mycosis was
      diagnosed by histological identification of intracellular hyphae of Histoplasma
      capsulatum. Laryngoscopy revealed edema, erythema and leukoplakia of the righ
      vocal cord. Itrakonazole treatment was successful. The relevant literature is
      reviewed.

PMID- 8554829
TI  - [Laryngeal fibrolipoma: a case report].
AB  - A case of laryngeal fibrolipoma, a rare tumor, is presented. The histopathology,
      symptoms, diagnosis, treatment, and related literature are reviewed.

PMID- 8554830
TI  - [Jugular vein thrombosis: a case report].
AB  - Thrombosis of the internal jugular vein is now rare but was well-known in the pre
      antibiotic era, when it was associated with fulminant infections of the head and
      neck. Now the two major causes of jugular thrombosis are central venous
      catheterization and intravenous drug use. The clinical findings are a non
      specific, painful, poorly delimited mass in neck that often is confused with an
      abscess or metastasis. CAT is necessary for diagnosis. We report a case secondary
      to central venous catheterization in which the clinical manifestations appeared
      three days after removing the catheter. The differential diagnosis of regional
      inflammations is described.

PMID- 8554831
TI  - [Immunohistochemistry: another criterion for typing oncocytomas of the salivary
      gland. A case report].
AB  - Oncocytoma of the salivary gland is uncommon and its histogenesis and pattern of
      evolution are debated. The criteria for malignancy are not well established. We
      report a morphologically benign oncocytoma of the parotid gland that was studied
      using various cell proliferation and tumor markers. These markers may have
      prognostic value and correlate with the aggressiveness of the tumor.

PMID- 8554832
TI  - [Tumors of the carotid body. A case report].
AB  - Tumors of the carotid body are uncommon. This primary neoplasm arises from the
      paraganglionar cells located at the bifurcation of the common carotid artery.
      They are usually multicentric and bilateral. Most patients consult for a painful,
      pulsatile mass situated in the angle of the jaw. Diagnosis is based on contrast
      CT, MRI and angiography. The treatment of choice is selective embolization
      followed by surgery.

PMID- 8554833
TI  - [Myringoplasty using a fat graft].
AB  - A technique for closing small tympanic perforations with a fat graft taken from
      the ear lobe is described. Our results and those of other authors are summarized
      and the advantages of the technique are detailed.

PMID- 8554834
TI  - Anecdotes and empiricism.

PMID- 8554835
TI  - There is hope yet for the development of primary health care in deprived areas.

PMID- 8554836
TI  - How does the content of consultations affect the recognition by general
      practitioners of major depression in women?
AB  - BACKGROUND: Major depression is a common and disabling condition. However, for
      many reasons, the condition is not recognized in about half of the patients with
      major depression. AIM: The aim of the study was to establish whether the content
      of general practice consultations affected general practitioners' recognition of
      major depressive illness in women patients. METHOD: The 30-item general health
      questionnaire was used as a first stage screening instrument for psychiatric
      morbidity. Patients newly recognized as depressed by their general practitioner
      and those not recognized as depressed who scored 11 or more on the questionnaire
      were interviewed, usually within three days of consulting their general
      practitioner, using the combined psychiatric interview. Videorecordings of the
      consultations for these two groups of women were analysed; analyses were based on
      mentions of physical, psychiatric and social symptoms and on whether the first
      mention of a psychiatric symptom was within the first four mentions of any
      symptoms (early in the consultation) or after four mentions of any symptoms
      (late) or if psychiatric symptoms were not mentioned. RESULTS: A paired sample of
      72 women with major depression was obtained from patients consulting 36 general
      practitioners, each general practitioner providing one patient whom he or she had
      correctly recognized as being depressed and one patient whose depression had not
      been recognized. Women with major depression were about five times more likely to
      have their depression recognized if they mentioned their psychiatric symptoms
      early in the consultation compared with those who either left it later to mention
      such symptoms or never mentioned them. Major depression was more likely to be
      recognized if no physical illness was present. After adjusting for physical
      illness, depression was 10 times less likely to be recognized if the first
      psychiatric symptom was mentioned late in the consultation, or not mentioned at
      all, than if it was mentioned early in the consultation. CONCLUSION: General
      practitioners need to remember that patients who present with symptoms of
      physical illness may also have depression. They also need to remember to give
      equal importance diagnostically to mentions of symptoms at whatever point they
      occur in the consultation, regardless of the presence or absence of physical
      illness.

PMID- 8554837
TI  - Assessing the outcome of making it easier for patients to change general
      practitioner: practice characteristics associated with patient movements.
AB  - BACKGROUND: The government white paper, Promoting better health, suggested that
      primary health care services should be made more responsive to patient needs and
      that competition, brought about by the freer movement of patients between
      practices, could act as a mechanism for improving the quality of the services
      provided. Policy changes reflecting these aims were introduced with the 1990
      contract for general practitioners. AIM: A study was carried out to estimate the
      volume of patient movement between practices not attributable to a patient's
      change of address or to a major change in the practice they had left, and to
      investigate which practice characteristics patients moved towards and which they
      moved away from when changing general practitioner. METHOD: Data on 2617 patient
      movements during June 1991 were collected from five family health services
      authorities. These patient movements were analysed in relation to data on
      practice characteristics obtained from family health services authority records.
      RESULTS: The estimated volume of movement of patients between practices was small
      (1.6% of the registered population per year). The majority of movements were
      between group practices; a quarter of the movements recorded were to single
      handed general practitioners. However, the ratio of the number of movements from
      group practices to single-handed general practitioners compared with those from
      single-handed general practitioners to group practices was 1.37 (95% confidence
      interval 1.19 to 1.57). In choosing single-handed general practitioners these
      patients were willing to forgo access to a woman general practitioner, extended
      services and greater hours of general practitioner availability. Among the subset
      of movements between group practices, patients were more likely to gain access to
      a practice nurse, longer surgery hours and a woman general practitioner as a
      consequence of their move. CONCLUSION: The scale of patient movement observed did
      not indicate any substantial mechanism by which the new policy of encouraging
      consumerist behaviour on the part of primary care users could effect desired
      changes in primary care practice. Among the patient movements observed, the
      evidence suggests that when choosing a practice potential patients were not
      deterred by the fact that a practice was single-handed. The public's perception
      of the factors contributing to a high quality of service may conflict with the
      official characterization of good practice and high quality services in primary
      health care.

PMID- 8554838
TI  - Investigation of the efficacy of progesterone pessaries in the relief of symptoms
      of premenstrual syndrome. progesterone Study Group.
AB  - BACKGROUND: A variety of definitions have been applied to premenstrual syndrome.
      The severity of the syndrome is also variable. AIM: A study was undertaken to
      compare progesterone pessaries with placebo in the relief of symptoms of
      premenstrual syndrome. In this study the condition was characterized by a wide
      range of symptoms recurring in the late luteal phase but absent in the follicular
      phase (that is, the specific definition published by Dalton in 1953). METHOD: A
      multicentre, prospective, double-blind, randomized, parallel group study was
      undertaken by 45 general practitioners. Patients were deemed eligible after two
      prospective menstrual cycles of observation (selection phase) in which a precise
      definition of symptoms was applied. Patients were randomized to use either
      progesterone pessaries (400 mg twice a day) or matching placebo, by vaginal or
      rectal administration, from 14 days before the expected onset of menstruation
      until the onset of vaginal bleeding, for four consecutive cycles. Baseline data
      for the outcome variables were determined in the selection phase. The main
      outcome variables were changes in the severity (categorized as none, mild,
      moderate or severe) of each patient's most severe symptom, and in the average
      score of all the patient's symptoms characteristic of premenstrual syndrome.
      Spontaneous reports of adverse events were recorded. RESULTS: A total of 281
      patients were screened for premenstrual syndrome; of these, 141 patients were
      randomized to treatment or placebo groups. Efficacy was evaluated in 93 patients.
      Reductions in the scores of the highest scoring, most severe, symptoms and in the
      average symptom score, were consistently observed in patients receiving
      progesterone pessaries and in those receiving placebo. The response to
      progesterone was greater than to placebo during each cycle; the differences were
      clinically and statistically significant. Adverse events were reported by 51% of
      patients in the progesterone treatment group and by 43% in the placebo group.
      Irregularity of menstruation, vaginal pruritus and headache were reported more
      frequently by patients taking active therapy. CONCLUSION: In this study,
      progesterone, given as pessaries by vaginal or rectal administration, was more
      effective than placebo in the relief of symptoms of premenstrual syndrome in a
      population of patients selected by strict entry criteria.

PMID- 8554839
TI  - Variation in prescribing of hypnotics, anxiolytics and antidepressants between 61
      general practices.
AB  - BACKGROUND: Although the desirability of reducing prescribing of hypnotics and
      anxiolytics has long been recognized, variation between practices in patterns of
      psychotropic drug prescribing has received little attention; factors underlying
      such variation are poorly understood. AIM: The study aimed to describe the extent
      of variation between general practices in the prescribing of hypnotics,
      anxiolytics and antidepressants; it also aimed to analyse the influence of
      measures of practice population and general practice and general practitioner
      characteristics on any variation in prescribing volumes. METHOD: Routinely
      collected prescribing data and practice population data, from April 1992 to March
      1993, from all 61 practices in the Cambridge and Huntingdon Health Commission
      were analysed. Prescribing was measured as annual defined daily doses per 1000
      practice population for each drug class. Data on variables relating to practice
      structure and general practitioner characteristics were obtained and analysed.
      Potentially influencing variables were investigated by multiple regression.
      RESULTS: Between the highest and lowest prescribing practices there was an 11
      fold difference, a 13-fold difference and an eightfold difference in the annual
      defined daily doses per 1000 practice population prescribed for hypnotics, for
      anxiolytics and for antidepressants, respectively. Strong positive correlations
      existed between volumes of prescribing of each drug class. The drugs prescribed
      in the greatest volumes were hypnotics. Practice population structure had some
      influence on psychotropic drug prescribing with high prescribing being associated
      with the proportions of temporary residents and women aged 65 years and over in
      the practice for all three classes of drug. Other factors, including presence of
      a practice counsellor, were not found to have a significant influence on
      psychotropic drug prescribing. CONCLUSION: The degree of variation in prescribing
      volumes of psychotropic drugs between practices raises serious concerns. Further
      study is needed, but progress will be hampered until there is more clarity over
      the effectiveness and appropriateness of using these substances in the various
      illness, symptom and life-stress presentations seen in primary care.

PMID- 8554840
TI  - General practitioner registrars' views about a career in general practice.
AB  - BACKGROUND: Current low morale in general practice and the fall in the number of
      general practitioner registrars (trainees) has led to concern about the decline
      in popularity of general practice as a career. AIM: A study was performed to
      evaluate the career intentions of general practitioner registrars and the factors
      underlying their decisions. METHOD: An anonymous postal questionnaire seeking
      both quantitative and qualitative data was sent to 138 registrars during June
      1993. All were registrars at practices in the south west region of England.
      Outcome measures used were the popularity of different types of general practice
      work and identification of variables and emergent themes considered important in
      career choice. RESULTS: A total of 101 registrars returned questionnaires (73%).
      Of the respondents, 96% expressed an interest in general practice as a career.
      However, registrars expressed considerable uncertainty about the future of
      general practice and therefore their career. Continuity of care and a holistic
      approach were considered valued aspects of work in general practice. Increased
      workload, increased out-of-hours work and erosion of professional autonomy
      emerged as negative aspects of a career in general practice. Of the respondents,
      91% considered time for leisure activities an important factor when considering
      future career, 72% would have been glad to do away with 24-hour cover and 99%
      agreed that general practitioners increasingly fear litigation. CONCLUSION:
      Although registrars were interested in general practice as a career they had many
      concerns and expressed uncertainties. The future popularity of general practice
      is likely to depend on addressing these concerns and on the clarification of the
      future direction of the profession.

PMID- 8554841
TI  - Audit and summative assessment: a criterion-referenced marking schedule.
AB  - BACKGROUND: 1996 will see the introduction of summative assessment of general
      practitioner registrars (trainees). One part of this assessment is the written
      submission of practical work. In the west of Scotland, audit projects have been
      chosen as the format for practical work. A valid and reliable marking schedule
      for such projects is needed. AIM: A study was undertaken to develop a criterion
      referenced marking schedule for assessing registrars' audit projects for
      summative assessment. METHOD: Medical and non-medical professionals, in a series
      of workshops, compiled a list of essential elements of good audit. These features
      were tested and refined using registrars' audit projects. All trainers in the
      west of Scotland were then sent a list of 14 criteria and asked to indicate
      whether each criterion was an essential or desirable component of a registrar's
      audit project for summative assessment. A final workshop was held to develop an
      audit marking schedule. RESULTS: Of 155 trainers in the west of Scotland, 135
      replied to the list of criteria for registrar audit projects (87%). Ten criteria
      were deemed essential or desirable by 80% or more of the respondents.
      Participants in the final workshop selected five criteria which would form the
      audit project marking schedule for registrars undergoing summative assessment.
      These were: defined reason for choice of audit project, relevance of criteria
      chosen, appropriate preparation and planning, appropriate interpretation of
      relevant data and detailed proposals for change. For an audit project to pass
      assessment all five criteria must be present. CONCLUSION: A criterion-referenced
      approach to assessing registrars' audit projects, developed from their trainers'
      opinions of essential or desirable criteria for good audit, is described. Further
      evaluation of the criterion-referenced marking schedule is required.

PMID- 8554842
TI  - Patients with urinary tract infection: proposed management strategies of general
      practitioners, microbiologists and urologists.
AB  - BACKGROUND: It is difficult to implement change in general practice. It is not
      known how best to conduct effective continuing medical education in general
      practice. General practitioners' criteria for good clinical practice vary and it
      is unknown whether systematic education by hospital specialists could be expected
      to reduce variation between general practitioners. AIM: A study was undertaken to
      describe general practitioners', microbiologists' and urologists' strategies for
      diagnosis, treatment, and follow up of female patients with symptoms of urinary
      tract infection, a common reason for consultation in general practice. The
      findings of the study were to be used as a base upon which to discuss the
      advantages and disadvantages of using hospital specialists as a resource in
      general practitioners' peer group based continuing medical education. METHOD:
      Three vignettes together with several proposals for diagnosis, treatment and
      follow up were presented in a questionnaire to general practitioners,
      microbiologists and urologists in Denmark. The case histories concerned three
      female patients (aged 10, 30 and 60 years) who consulted their general
      practitioner for advice. The female patients were otherwise healthy and well
      known to the practice. General practitioners', microbiologists' and urologists'
      recommendations for good clinical practice were compared. RESULTS: A total of 154
      general practitioners (77%), 45 microbiologists (51%) and 54 urologists (61%) who
      were eligible for the study responded to the questionnaire. There was
      considerable variation in the management strategies proposed by doctors within
      each specialty and between the specialties. Microbiologists and urologists were
      more likely to suggest treating the 30-year-old woman by giving advice and a
      prescription by telephone compared with their general practitioner colleagues.
      Conversely, the microbiologists and urologists were more likely to suggest asking
      the 10- and 60-year-old patients to attend the clinic for examination compared
      with the general practitioners. The general practitioners reported asking the
      patients to return for follow up more commonly than the hospital specialists.
      CONCLUSION: Large variation in suggested strategies for diagnosis, treatment and
      follow up was shown both within and between specialties. Continuing medical
      education of general practitioners based on small peer group discussions using
      hospital specialists as a group resource would not necessarily reduce variation
      in clinical practice between general practitioners. A need for evidence-based
      rather than consensus-directed guidelines would be needed in order to reduce
      variation in clinical practice between doctors.

PMID- 8554845
TI  - Preventing teenagers from starting smoking.

PMID- 8554844
TI  - Primary care research ethics.
AB  - Research activity in primary care is increasing rapidly, and raises a range of
      specific ethical issues. Many of these relate to the involvement of individuals
      in the community who are not seeking medical care and to the impact of research
      participation on relationships between general practitioners and their patients.
      The ethical issues pertinent to a range of quantitative and qualitative research
      methodologies in primary care are identified and considered.

PMID- 8554843
TI  - General practice update: chlamydia infection in women.
AB  - The prevalence of cervical Chlamydia trachomatis infection in general practice
      populations ranges between 2% and 12%. Untreated infection can cause pelvic
      inflammatory disease, tubal infertility and ectopic pregnancy. These risks are
      increased by cervical invasive procedures, especially termination of pregnancy.
      However, most women with chlamydia infection have no symptoms. General
      practitioners and practice nurses carrying out pelvic examinations should have
      facilities for taking endocervical specimens for chlamydia. Routine chlamydia
      screening, should be considered if the local prevalence of infection is over 6%.
      Otherwise chlamydia testing should be offered to women requesting termination of
      pregnancy and to those who have risk factors: aged less than 25 years, absence of
      barrier contraception, recent change of sexual partner, vaginal discharge,
      friable cervix or sterile pyuria. Women found to have chlamydia infection need
      appropriate antibiotics, advice about contact tracing and referral to a
      genitourinary medicine clinic. Good communication between general practitioners
      and genitourinary physicians is essential. Both general practitioners and
      practice nurses have an important role to play in reducing the prevalence of
      cervical chlamydia infection and its potentially devastating consequences.

PMID- 8554846
TI  - Homoeopathy and immunization.

PMID- 8554847
TI  - Cancer patients' place of death.

PMID- 8554848
TI  - Videotaped consultations.

PMID- 8554849
TI  - Videotaped consultations.

PMID- 8554850
TI  - Acute myocardial infarction.

PMID- 8554851
TI  - Fetal echocardiography.
AB  - Fetal echocardiography has provided a means for the detailed assessment of
      cardiac structure and function from early prenatal life. Indications for a fetal
      echocardiographic examination and the potential implications for individuals
      caring for newborns with cardiac malformations are discussed.

PMID- 8554852
TI  - Factors that influence the choice of infant feeding.
AB  - To consider some of the many factors that influence the choice to initiate and
      continue breast-feeding. CONCLUSION: There is increasing recognition of the
      nutritional value and related health outcomes of breast-fed infants. Further
      research is essential to appraise the medical and social determinants of infant
      feeding practices, particularly the early discontinutation of breast-feeding.
      Paediatricians are in an ideal position to foster, encourage and support such
      research and to accept a wider role in advocacy of the infant's right to obtain
      optimal nutrition.

PMID- 8554853
TI  - Molecular genetics of Wilms' tumour.
AB  - Wilms' tumour, or nephroblastoma, is an embryonal malignancy of the kidney with
      an incidence of approximately 1 in 10,000 live births. It occurs in both sporadic
      and familial forms, but only 1% of Wilms' tumour patients have a positive family
      history. The molecular genetics of Wilms' tumour have been the subject of
      extensive research and at least three genes (WT1, WT2, WT3) have been implicated.
      WT1 has been mapped to 11p13, and it has been suggested that loss or inactivation
      of a tumour-suppressor gene at 11p13 might be a primary event in the development
      of Wilms' tumour. The WT2 gene maps to 11p15 in the region of the Beckwith
      Wiedemann locus. The WT3 locus is likely to be located to chromosome 16q. The
      understanding of the molecular genetics of Wilms' tumour is reviewed briefly.

PMID- 8554854
TI  - Of colic and rumbling in the guts.
AB  - Infant colic is a common disorder of doubtful aetiology. The known facts have
      been interpreted in a historical and geographical context. The apparent increase
      in incidence of the condition in the Westernized world during the twentieth
      century may reflect the technological advances and social changes that have
      occurred in recent years.

PMID- 8554855
TI  - A prospective study of nosocomial infection in a neonatal intensive care unit.
AB  - OBJECTIVE: To determine the incidence of and organisms responsible for neonatal
      nosocomial infection (after 72 h of age). METHODOLOGY: A 1-year evaluation of 321
      consecutive septic work-ups performed on 130 of 1008 babies admitted to a
      neonatal intensive care unit (NICU) for more than 72 h. Fifty-seven (89%) of 64
      infants of birthweight 500-999 g, 36 (34%) of 105 infants 100-1499 g, 27 (6%) of
      422 infants 1500-2499 g and 10 (28%) of 477 infants of birthweight > 2500 g had
      at least one septic work-up. RESULTS: In addition to blood culture, the
      evaluations included haematological score on full blood count in 94.7%, abdominal
      X-ray in 48%, endotracheal tube tip culture in 32.7% and lumbar puncture in only
      13.1%. Blood culture was positive on 92 occasions in 75 infants (28.7% of work
      ups and 7.4% of all babies admitted). Infection status was classified as definite
      on 40 occasions in 30 babies, and due to contamination 52 in 45 babies. Twenty of
      the 30 babies with definite infection were of birthweight 500-999 g. Of the 40
      definite infections coagulase-negative staphylococci (CONS) were cultured from 23
      babies, Gram negative bacilli in 14 and Candida spp. in three babies. Sepsis
      caused or contributed to the deaths of six babies. CONCLUSION: This study
      identifies infants of birthweight < 1000 g as the highest risk group for
      nosocomial infection especially CONS. New strategies in prevention, surveillance
      and treatment are required for extremely low birthweight infants.

PMID- 8554856
TI  - Influence of families on the growth of children in an aboriginal community.
AB  - OBJECTIVE: Some Aboriginal children have poor growth while others grow according
      to international standards. This study was designed to find whether these
      differences were related to families. METHODOLOGY: Data were obtained on 13
      families at Cherbourg Aboriginal Community in Queensland. There were data on the
      growth and hospital admissions of children in these families for at least two
      generations. Data were taken from records of the Infant Health Clinic and
      Hospital on the Community. A total of 606 children were considered. RESULTS: The
      growth of a child during infancy is correlated with the growth of his/her mother
      in infancy, but not with the growth of the father. We have therefore defined
      families in the matrilineal line. There were marked and highly significant
      differences between the growth of children in the 13 families. The families with
      good growth in one generation were likely to have good growth of children in the
      next generation. CONCLUSIONS: In spite of the overall improvements in the growth
      of infants and children at Cherbourg, families tended to maintain their rankings
      from one generation to the next. It would be cost-efficient to target health
      advice to those families who have, in the past, had poor growth among their
      children.

PMID- 8554857
TI  - Status epilepticus in 37 Chinese children: aetiology and outcome.
AB  - OBJECTIVE: The aetiology and clinical features of status epilepticus (SE) are
      described, with the aim of defining any relationship between risk factors and
      clinical outcome. METHODOLOGY: A retrospective review was performed of 37 Chinese
      children admitted to Queen Mary Hospital, Hong Kong, from 1989 to 1993 with the
      diagnosis of SE. RESULTS: Eighty-six per cent had onset before 5 years of age;
      60% were due to an acute central nervous system (CNS) insult, 11% were
      idiopathic, 13% had a pre-existing CNS insult, 5% were febrile and 11% were due
      to progressive encephalopathy. An abnormal neurological status was present in 24%
      before the episode of SE, and a history of seizures before the onset of SE was
      present in 35% of patients. Fifty-four per cent of the episodes of SE were
      generalized. The mortality rate was 11% during the period of follow up but no
      deaths were attributed to SE. Neurological sequelae were observed in 27% of
      patients and recurrent SE occurred in 12%. CONCLUSIONS: In those patients with
      normal neurological status before an episode of SE and without acute CNS insult
      or progressive encephalopathy, the outcome was favourable.

PMID- 8554858
TI  - Inferior vena cava pressure as an estimate of central venous pressure.
AB  - OBJECTIVE: To determine whether pressure in the inferior vena cava (IVC) is
      similar to central venous pressure. METHODOLOGY: Prospective measurement of both
      central venous pressure (CVP) and inferior vena cava pressure (IVCP) in the same
      child; each child had to have both catheters in situ. Two measurements of each
      pressure in reverse order (IVCP then CVP, and CVP then IVCP) were done and the
      mean of each was recorded. Comparison of the pressures was performed using the
      method of Bland and Altman. RESULTS: Thirty-nine children had pressures recorded.
      The CVP ranged from 3 to 17 mmHg. In 22 of 39 measurements IVCP was equal to CVP;
      in 33 of 39 measurements IVCP was different from CVP by 1 mm or less and in 37 of
      39 measurements IVCP was different from CVP by 2 mm or less. The mean difference
      between IVCP and CVP was +0.33 mmHg, the 95% confidence interval was 2.26 to
      +2.93 mmHg. CONCLUSION: Measurement of IVCP is a good approximation to CVP and
      can be routinely used in clinical care of children who do not have raised intra
      abdominal pressure.

PMID- 8554859
TI  - Growth, development and behaviour in adolescents born small-for-gestational-age.
AB  - OBJECTIVE: To examine the effects on adolescents of being born small-for
      gestational-age (SGA). METHODOLOGY: The sample are members of a cohort
      longitudinal study in which growth, cognitive development and behaviour are being
      studied into adulthood. Ninety-one SGA subjects were available for comparison
      with the rest of the sample (n = 1037) on measures of height, weight, head
      circumference, cognitive performance and behavioural variables to the age of 18
      years old. RESULTS: SGA subjects were shorter and lighter at 18 years of age than
      their appropriate-for-gestational-age (AGA) counterparts despite age of onset of
      menarche being the same in both groups. At age 13, SGA subjects scored
      significantly lower than the AGA group on the WISC-R scales. They were rated by
      parents as having more behaviour problems at age of 15. CONCLUSIONS: SGA birth
      appears to be a potential problem which extends beyond childhood in its effects
      on growth, behaviour and cognitive performance.

PMID- 8554860
TI  - Higher rates of SIDS persist in low income groups.
AB  - OBJECTIVE: To examine how changes in the rates of sudden infant death syndrome
      (SIDS) have varied in different income groups during a 25 year period.
      METHODOLOGY: Census data were obtained for five census periods (1971, 1976, 1981,
      1986 and 1991) on the number of SIDS cases and inevitable deaths. Census area
      units (CAU) were ranked according to the average income earned by adults over the
      age of 15 years for each census year. The CAU were then divided into three equal
      income groups: low, middle and high. RESULTS: The rates of SIDS differed
      significantly between the three income groups for the 1991 census period with the
      low income SIDS rate being 4.6/1000 births compared to 1.2/1000 live births for
      the higher income groups (Chi-squared = 18.3, P < 0.0001). There was no
      association between rates of inevitable deaths and income groups. CONCLUSION:
      Currently, low income groups have three times the rate of SIDS compared to those
      in higher income groups. The reason for this is probably because the
      disadvantaged groups carry an overall higher burden of risk factors for SIDS.
      This must be kept in mind as further SIDS educational programmes are developed
      and implemented.

PMID- 8554861
TI  - A pilot evaluation of conductive education-based intervention for children with
      cerebral palsy: the Tongala project.
AB  - OBJECTIVE: To perform an objective evaluation of a programme based on conductive
      education (CE). METHODOLOGY: Two groups of children with cerebral palsy were
      studied over 6 months. Eleven children participated in a CE-based programme and
      nine children received traditional early intervention programmes. Videotapes of
      the children performing items from the Vulpe Assessment Battery (VAB) were scored
      by assessors blind to the treatment group. The questionnaire on resources and
      stress (QRS-F) was administered to the primary caregiver. RESULTS: Few
      statistically significant results were obtained. There was a trend for the
      conductive education-based group to make slightly greater gains. The videotaped
      measures yielded high Chronbach coefficients and high interrater correlation
      coefficients suggesting that this is a useful method to evaluate progress.
      CONCLUSIONS: The study was limited by small sample size, the nature of the
      control group and the lack of random assignment to CE and control groups. It did
      provide a basis for the development of further research in the area.

PMID- 8554862
TI  - Evaluation of an early childhood programme based on principles of conductive
      education: the Yooralla project.
AB  - OBJECTIVE: To perform an objective evaluation of a programme based on conductive
      education (CE) for preschool and early school-aged children with cerebral palsy.
      METHODOLOGY: The progress of 17 children participating in a CE-based programme
      (the Yooralla programme) was compared with 17 children enrolled in traditional
      early childhood services. Videotapes of the children performing items from the
      Vulpe Assessment Battery (VAB) were scored by assessors blind to the treatment
      group; three standardized tests of cognitive ability were administered; and the
      questionnaire on resources and stress (QRS-F) was given to the primary caregiver
      at the beginning and conclusion of 6 months. RESULTS: The Yooralla group improved
      in motor performance and parental coping variables. Both groups showed
      improvement on the cognitive measures, with the control group demonstrating
      slightly greater gains. CONCLUSIONS: Conductive education may benefit the motor
      development of children with cerebral palsy and provide greater parental support.
      A randomized control study with adequate subject numbers is necessary to confirm
      this tentative conclusion.

PMID- 8554863
TI  - Health status of Victorian special school children.
AB  - OBJECTIVE: This study sought to determine the health status and health needs of a
      sample of students attending special schools for the intellectually disabled in
      Victoria, Australia. METHODOLOGY: Two hundred and forty-nine students not
      previously seen by a Community Child Health Medical Officer (CCHMO) were assessed
      at school. Data on student, parent and staff needs were obtained through personal
      interviews and documented on a standard questionnaire. Health status was
      documented using data obtained from parents and teachers as well as the clinical
      assessment. RESULTS: Comparison of the number of problems reported by parents
      with the number confirmed at examination showed significant underreporting of
      vision, hearing and general medical problems. However, behaviour problems were
      nearly all reported. Many students had multiple problems with 63% having 2-4
      problems and 11% having 5-8 problems. Ninety-nine (40%) of the 249 children seen
      had newly detected problems; vision (24), hearing (24) and obesity (9) were the
      most common. Two hundred and forty-four (98%) had known problems and 27% of these
      had insufficient information available from parents or staff to completely
      ascertain their health status. In 115 cases the primary problem was intellectual
      impairment of unknown cause. Down's syndrome was the next most common underlying
      diagnosis (30) followed by autism (24), epilepsy (21) and cerebral palsy (15).
      The most common secondary diagnoses were asthma (16), congenital heart defects
      (12), seizures (8) and skin problems (8). Many students required referral for
      further management both for newly detected problems (64%) and known problems
      (18%). Parents required counselling and/or discussion on a number of issues for
      both newly detected problems (66%) and known problems (39%); when counseling had
      taken place parent and staff concerns had reduced significantly by the time of
      the follow-up assessment. CONCLUSIONS: This study demonstrates that in those
      students with known intellectual impairment there were many with other
      unrecognized health problems and unmet needs. These findings have implications
      for health services provided to children attending special schools.

PMID- 8554865
TI  - Parent satisfaction with services in an emergency department located at a
      paediatric teaching hospital.
AB  - OBJECTIVE: To evaluate parents' satisfaction with the services provided in an
      emergency department located at a paediatric hospital. METHODOLOGY: A descriptive
      study in which the parents of children with non-life-threatening illnesses
      attending an emergency department completed a questionnaire describing their
      satisfaction with services in the department. RESULTS: The majority of parents
      were satisfied with the services provided. However, less satisfied parents
      reported having to wait significantly longer before receiving medical attention
      than satisfied parents. Consistent with this finding, 77% of less satisfied
      parents reported that staff did not attend to their children's needs quickly
      enough and 62% felt that there were insufficient staff available to provide help.
      Twenty-nine per cent of the less satisfied parents reported that they did not
      know what was required for the ongoing care of their children after their
      discharge from the emergency department. CONCLUSIONS: In order to address the
      concerns of less satisfied parents, emergency departments need to give careful
      attention to the maintenance of reasonable waiting times, the provision of
      adequate staffing, and the quality of staff-parent communication. Addressing
      these issues may improve the ongoing care of children after their discharge from
      emergency departments.

PMID- 8554864
TI  - Incomplete catch-up growth in low birthweight Chinese infants in Hong Kong.
AB  - OBJECTIVE: To describe the early catch-up growth in length in Chinese low
      birthweight (< 2500 g) infants. METHODOLOGY: The infants (n = 181) were delivered
      between 1988 and 1993 and followed up at Queen Mary and Tsan Yuk Hospitals, Hong
      Kong. One third had a birthweight below -2SDS, most of whom were term or close-to
      term babies small-for-gestational-age (SGA). The remaining babies were
      appropriate-for-gestational-age (AGA) in birthweight, but frequently born
      prematurely. RESULTS: The SGA group did not show a catch-up growth in height
      comparable to that reported on other recent studies, as 33-35% of the patients
      were still short at 6 and 12 months (7-12% for the AGA group). When comparing the
      postnatal mean growth curve of the SGA group with the mean curve of the AGA group
      there was little sign of catch-up growth. CONCLUSIONS: The results showed that
      Hong Kong SGA infants have an incomplete catch-up growth and for successful
      intervention the causative mechanisms have to be identified.

PMID- 8554866
TI  - Psychological outcome of ECMO-eligible neonates with severe respiratory failure
      treated using conventional medical therapy.
AB  - OBJECTIVE: The present study addressed a National Health and Medical Research
      Council (NHMRC) recommendation that the outcome of neonates who are treated
      conventionally for respiratory problems be further investigated before setting up
      additional extracorporeal membrane oxygenation (ECMO) centres in Australia.
      METHODOLOGY: The cognitive and behavioural outcome of ECMO eligible infants who
      received conventional treatment for respiratory problems at birth was assessed in
      18 infants aged 1.5-3 years (index group). ECMO was not available at either of
      the treating hospitals. Index children were compared to a matched control group
      of children who did not experience any major complications at birth. Children
      were assessed using either the Bayley or McCarthy scales of infant development
      and the Child Behavior Checklist. RESULTS: Overall, a mortality rate of 19% and a
      psychological morbidity rate of 18% suggest that children born with severe
      respiratory failure, who meet existing ECMO eligibility criteria, have a good
      prognosis when treated using conventional medical therapy. CONCLUSIONS:
      Improvements to conventional treatments indicate that ECMO eligibility criteria
      may need to be revised to identify accurately those infants who are at extreme
      risk of mortality if treated conventionally.

PMID- 8554867
TI  - Perinatal mortality trends among South Australian aboriginal births 1981-92.
AB  - OBJECTIVE: To assess changes in perinatal mortality and risk factors for births
      to Aboriginal mothers in South Australia in 1981-92. METHODOLOGY: All 4013
      singleton Aboriginal births in the South Australian perinatal data collection
      were included. Trends in proportions with specific maternal and infant
      characteristics, and perinatal mortality by year of birth, were investigated by
      logistic regression analysis. RESULTS: Changes found included an increase in the
      proportion of mothers aged 35 years and over, preterm births and births of very
      low birthweight (< 1500 g), but a decrease in the proportions of births to women
      under 20 years of age, and of births with a birth defect. There was no
      statistically significant change in the crude perinatal mortality rate nor in the
      risk of perinatal death after adjusting for risk factors. CONCLUSIONS: The
      perinatal mortality rate among Aboriginal births, which is three times higher
      than the rate for all South Australian births, is not declining, in contrast to
      the State rate overall. This highlights the need for a concerted approach to
      Aboriginal perinatal health.

PMID- 8554868
TI  - Changing patterns of survival and outcome at 4 years of children who weighted 500
      999 g at birth.
AB  - OBJECTIVE: To evaluate the impact of changing perinatal practices on survival
      rates and 4 year neurodevelopmental outcome for infants of birthweight 500-999 g.
      METHODOLOGY: The study was a tertiary hospital-based prospective cohort study
      that compared survival, impairment and handicap rates between two eras, July 1977
      to December 1982 (era 1) and January 1983 to June 1988 (era 2). All 348 live,
      inborn infants and 49 outborn infants of birthweight 500-999 g were prospectively
      enrolled in a study of survival and outcome. Rates of survival,
      neurodevelopmental impairment and functional handicap at 4 years were compared
      between eras. Perinatal risk factors for handicap were also compared between
      eras. RESULTS: Four year survival rates for inborn infants 500-999 g improved
      from 32.6% in era 1 to 49.2% in era 2 (OR 2.1, 95% CI 1.26-3.48) but for outborn
      infants the improvement between 31.8% and 53.6% was not significant. There were
      significant improvements in survival for inborn infants in birthweights 800-899 g
      and 900-999 g between study periods. The rates of functional handicap between the
      first and second eras (mild 10 vs 7%; severe or multiply severe 14 vs 16%) were
      not significantly different. Although the rate of cerebral palsy increased from 0
      to 12% (P < 0.01) other rates of impairment such as blindness 0 vs 3%, deafness 2
      vs 2% and developmental delay 12 vs 11% did not change. The chance of a survivor
      being free of handicap remained unchanged at 78% and 76% for the two eras,
      respectively. Although the absolute number of intact survivors more than doubled
      (41 vs 83) so too did the number of severe or multiply severe handicapped
      survivors (7 vs 17). Multivariate logistic regression analysis for the entire
      study cohort revealed male gender, multiple birth, prolonged mechanical
      ventilation and cerebral ventricular dilatation but not birthweight or
      gestational age to be independently associated with severe or multiply severe
      handicap. CONCLUSIONS: The advances in neonatal intensive care for extremely low
      birthweight infants between July 1977 and December 1982 and January 1983-June
      1988 resulted in an increased number of non-disabled survivors but had no impact
      on incidence of severe disability. The application of prediction of mortality or
      severe handicap to clinical practice has the potential to reduce the proportion
      and absolute number of severely handicapped survivors.

PMID- 8554869
TI  - Cleft palate, mortality and morbidity in infants of substance abusing mothers.
AB  - OBJECTIVE: To investigate a high incidence of congenital malformations, morbidity
      and mortality in infants of drug abusing mothers. METHODOLOGY: In a 10 and a half
      year period from 1984-95, 497 such babies were reviewed whose mothers had abused
      a variety of drugs. RESULTS: Thirty babies died or had serious disability. There
      were five cases of SIDS and 19 babies had major malformations, including seven
      with cleft lip/palate. Six babies had significant gastrointestinal disorders or
      feeding difficulties. CONCLUSION: The incidence of clefting was 10 times the
      normal rate and SIDS five times the expected incidence. In a group of mainly
      socially disadvantaged women, the abuse of narcotics, amphetamines and other
      substances, with possible suboptimal nutrition, may have been contributory to
      this high morbidity and mortality. No specific drug could be implicated.

PMID- 8554870
TI  - Aminophylline and Doppler time-averaged mean velocity in the middle cerebral
      artery in preterm neonates.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of an intravenous
      loading dose of aminophylline (6 mg/kg) on Doppler time-averaged mean velocity in
      the middle cerebral artery in ventilated preterm neonates. METHODOLOGY: Twenty
      infants were studied by colour/duplex Doppler technique prior to and at 5, 10, 30
      and 60 min after the administration of aminophylline. RESULTS: Aminophylline
      treatment was associated with a statistically significant reduction in time
      averaged mean velocity from baseline (P < 0.001) and an increase in heart rate (P
      < 0.001) at all timepoints. The largest reduction in time-averaged mean velocity
      of 19% (95% confidence interval -10 to -28%) occurred at 10 min post-dose. There
      were no statistically significant changes in transcutaneous PCO2 or mean arterial
      blood pressure. CONCLUSIONS: The observed reduction of 19% from baseline in time
      averaged mean velocity following treatment with aminophylline alone is unlikely
      to be of clinical importance. Whether aminophylline in combination with other
      drugs that decrease central blood flow velocity such as indomethacin and/or
      dexamethasone could result in a clinically significant reduction deserves further
      study.

PMID- 8554871
TI  - Use of simple clinical parameters to assess severity of bronchiolitis.
AB  - OBJECTIVE: To determine whether simple clinical parameters could be used to
      predict the severity of acute bronchiolitis and the need for supplemental oxygen
      therapy. METHODOLOGY: A prospective study, performed in a tertiary care
      paediatric hospital. Seventy-one infants under 15 months of age with a clinical
      diagnosis of acute bronchiolitis were examined on admission. Clinical parameters
      were recorded, and each infant was re-examined after approximately 12 and 24 h.
      All infants were examined by one medical student and, when possible, by a doctor,
      the two being unaware of each other's findings. Parameters recorded included
      respiratory and heart rates and presence of wheeze, crackles, intercostal
      recession, sternal retraction and/or cyanosis. The outcome measure was the need
      for supplemental oxygen, as determined by the independent caring medical team, on
      the basis of pulse oximetry and clinical judgement. RESULTS: Forty (56%) of the
      71 babies required supplemental oxygen. All cyanosed babies required supplemental
      oxygen, but only 9 (21%) were cyanosed on admission. Intercostal recession
      (relative risk RR 2.55; 95% CI 1.28, 5.08) and sternal retraction (RR 1.60; 95%
      CI 1.06, 2.42) predicted the need for supplemental oxygen with moderate accuracy.
      Interobserver agreement was only fair for most parameters, but was poor for
      intercostal recession and good for cyanosis. CONCLUSIONS: Simple clinical
      parameters may help predict the need for oxygen therapy in acute bronchiolitis,
      although further studies are required to define suitable clinical criteria. Such
      criteria are extremely important in developing countries where oxygen is a scarce
      resource.

PMID- 8554872
TI  - Factors associated with the age of introduction of solids into the diet of New
      Zealand infants. New Zealand Cot Death Study Group.
AB  - OBJECTIVE: To describe the current timing of the introduction of solids in
      infancy and the factors influencing the decision to introduce solids.
      METHODOLOGY: Eighteen hundred infants were selected randomly as part of the New
      Zealand Cot Death Study. Of these, 88% of the parent/caregivers were interviewed
      when their infant was aged between 1 and 12 months. They were asked when solids
      were first introduced into the diet. RESULTS: By 12 weeks of age more than 20% of
      infants had been given solids; by 16 weeks and by 6 months 50 and 90% of babies,
      respectively, had been given solids. Maternal smoking, low educational
      achievement and not being breast-fed exclusively to 4 weeks of age were factors
      which were strongly associated with the early introduction of solids. CONCLUSION:
      Half of New Zealand infants are being started on solids earlier than is presently
      recommended. More education is needed to promote the later introduction of solid
      foods into the diet.

PMID- 8554873
TI  - Antenatal and intrapartum factors associated with sudden infant death syndrome in
      the New Zealand Cot Death Study.
AB  - OBJECTIVE: To describe the relationship between antenatal and intrapartum factors
      and sudden infant death syndrome (SIDS). METHODOLOGY: The New Zealand Cot Death
      Study was a 3 year case-control study, with 485 infants who died from SIDS in the
      postneonatal period and 1800 randomly selected control infants. Data were
      obtained from obstetric records, parental interview and community nursing
      records. RESULTS: This study confirms many of the antenatal and intrapartum risk
      factors for SIDS noted in studies from both the southern and northern
      hemispheres. After controlling for potential confounders, such as occupational
      group and marital status, significant inverse effects were noted for
      interpregnancy interval, birthweight and gestation. Other factors that retained a
      significantly increased risk of SIDS were: increasing parity, bacteriological
      evidence of urinary tract infection (UTI) (adjusted odds ratio 1.73, 95% CI 1.10
      2.73); smoking antenatally (AdjOR 2.14, 95% CI 1.61-2.84); less than six
      antenatal checks attended (AdjOR 1.84, 95% CI 1.19-2.84); second stage of labour
      less than 16 min (AdjOR 2.06, 95% CI 1.35-3.14) and multiple birth (AdjOR 3.23,
      95% CI 1.70-6.02). No interaction was observed between maternal haemoglobin and
      antenatal smoking. Interactions were tested for and not found between antenatal
      smoking and three antenatal risk factors (UTI, short second stage of labour and
      number of antenatal appointments). The only significant interaction between these
      three factors and three modifiable postnatal risk factors (prone sleeping, bed
      sharing and bottle feeding) was between bed sharing and fewer antenatal
      appointments. The risk of SIDS associated with bed sharing was greater among
      those whose mothers had fewer antenatal appointments. CONCLUSIONS: Although many
      of the previously identified antenatal and intrapartum risk factors for SIDS are
      confirmed, the risks of SIDS associated with obstetric factors are in general
      considerably lower than the risks associated with the four modifiable postnatal
      risk factors.

PMID- 8554874
TI  - Hydrometrocolpos and segmental colonic dilatation in a girl with megacystis
      microcolon-intestinal hypoperistalsis syndrome.
AB  - OBJECTIVE: To report a case of a newborn female infant noted to have features of
      the megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) with the
      additional features of hydrometrocolpos and segmental colonic dilatation and
      review the literature. METHODOLOGY: The details of the case were collated and
      compared with the previous published experience with this condition. RESULTS:
      Thus far there have been 58 previous cases of MMIHS described, only four of which
      have had colonic dilatation. A number of concurrent anomalies have been
      described, but not the hydrometrocolpos or dysmorphic features seen in this
      patient. CONCLUSION: This case appears to be MMIHS with additional features not
      previously recorded.

PMID- 8554875
TI  - Intra-uterine varicella or herpes zoster and childhood deafness.

PMID- 8554876
TI  - Epidemic rickets in migrant families in Melbourne and Sydney.

PMID- 8554877
TI  - [Proton therapy in Japan].
AB  - Japan has the oldest experience in proton therapy outside the United States and
      Russia. The main treatment indications are hepatoma, lung and oesophageal
      carcinomas. The last center built in Chiba in the suburbs of Tokyo has two
      synchrotrons and three treatment rooms. Cost has been close to 2 billion French
      francs.

PMID- 8554878
TI  - [Neutron capturing irradiation: principle, current results and perspectives].
AB  - Neutron capture irradiation aims to selectively destroy the tumoral cells with
      nuclear reactions produced inside themselves. Therefore, 10B is selectively
      carried into tumours, being linked to a molecular vehicle. The tissues are then
      irradiated with thermal neutrons, and the boron neutron capture leads to the
      formation of alpha and 7Li particles which produce high levels of radiolytic
      damage along their range of 10 microns. Boron neutron capture therapy (BNCT) uses
      a thermal/epithermal neutron beam for irradiation, while boron neutron capture
      potentiation uses the addition of the captures in a fast neutron irradiation. A
      first trial, conducted in 1951 to 1961 in the USA to test BNCT on patients
      suffering of glioblastoma, was a failure, essentially because 10B was located in
      the cerebral capillaries rather than in the tumoral cells. Today, with great
      improvement in the boronated compounds which show an uptake preferentially inside
      the cells; the quality of neutron beams; and the knowledge of the microdosimetry
      of the technique, this technique may be clinically used to increase the local
      control of radioresistant tumours, like the high grade gliomas, cutaneous or
      uveal melanoma, and perhaps soft tissue sarcomas.

PMID- 8554879
TI  - [Brachytherapy of ocular melanoma: physical and dosimetric aspects of 125I
      plaques].
AB  - Off-axis absorbed dose distribution of ophthalmic plaques is a useful parameter
      for the explanation of some observed biological effects. From a specific
      dosimetric software, developed in our brachytherapy department, and from our
      measurements around 125I eye plaque, we studied the dose distribution effects on
      the spread of activities inside the plaques. After analysis of experimental data,
      we observed also that the dose distribution in the penumbra area may be described
      easily with decrement lines.

PMID- 8554880
TI  - [External electron irradiation in 2 cases of capillary hemangioma of the optic
      disk].
AB  - The authors report on two cases of solitary capillary hemangioma of the optic
      disc, treated with external electron beam. The radiotherapist must know these
      rare indications of radiotherapy; and though it is a benign tumor, fractionated
      irradiation with low doses is excellent and generally safe.

PMID- 8554881
TI  - [Evaluation of the importance of systematic neck dissection in carcinoma of the
      oral cavity treated by brachytherapy alone for the primary lesion (apropos of a
      series of 346 patients)].
AB  - The study includes 346 carcinomas of the oral cavity (244 mobile tongues and 102
      floors of mouth) treated by brachytherapy alone at primary tumor. We noted 199
      T1, 131 T2, 14 T3 and 2 TxNx. Among T1, 36 patients had a neck dissection as well
      as 73 T2. Brachytherapy was performed according to the Paris system. In 59 cases,
      the curage on the lesion side was a radical neck dissection, in 14 cases a
      functional neck dissection and in 45 cases a submaxillary and submental
      dissection. A combined controlateral neck dissection was performed in 20 cases. A
      complementary irradiation of the node areas was given in 28 cases. RESULTS: for
      T1, the local control (LC) is 96%, the locoregional control (LRC) 83%, the
      specific survival (SS) 88%, and the overall survival (OS) 73%. For T2, LC 85%,
      LRC 70%, SS 75%, OS 52%. For T3, LC 64%, LRC 44%, SS 25%, OS 18%. The difference
      is very significant between T1 T2 T3 (p < 0.006) for results concerning N0, it is
      not significant between the N1 in each category, but their number is too low to
      reach a degree of significancy. In the 36 neck dissection specimens of T1, we
      found only in 7 cases positive nodes and in the 73 specimens of T2, 24 cases of
      positive nodes. A detailed study is reported. Tumoral, node or both recurrences
      are summarized (see table IV). Node recurrences are more frequent in patients
      without neck dissection than in those with neck dissection for T1, T2, N0, but
      this is significant only for LRC, SS and OS between patients with negative nodes
      on neck dissection and those with positive nodes (p < 0.0001). No significant
      difference was found between OS and SS for patients T1, T2, N0 with positive
      systematic neck dissection and those with a neck dissection differed until the
      node recurrence. Among T1, T2, T3, we noted more metastases in patients who
      presented a recurrence than in others. In conclusion, for patients treated by
      brachytherapy alone to the primary lesion, it seems desirable to perform a
      systematic neck dissection if there are adenopathies on initial examination. The
      dissection can be delayed for small tumors T1 N0 and low T2 N0 if the patients
      are followed-up regularly. However, a systematic dissection must be advised for
      high T2 N0 and T3 N0 given the frequency of the node involvement and the risk of
      metastases.

PMID- 8554882
TI  - [Postoperative radiotherapy in carcinoma of the pyriform sinus. Work of the
      "Groupe radiotherapie de la Federation national des centres de lutte le cancer"].
AB  - Between January 1980 to December 1985, 248 patients with advanced squamous cell
      carcinoma of the pyriform sinus were retrospectively analysed. Criteria for
      inclusion in the study were the following: no previous treatment and treatment
      combining total pharyngolaryngectomy and postoperative radiotherapy. Mean follow
      up was 5 years with a minimum of 3 years. Seventy-one patients had a local
      regional recurrence (27.4%). Clinical staging at presentation and residual tumor
      at the primary site after surgery were factors significantly associated with
      higher local failure rates. The 5 year survival rate was 33% and the median
      survival time was 32 months (plateau was reached after the 6th year). The most
      frequent severe complication observed was pharyngeal stenosis occurring in 6% of
      the cases. This study confirms the poor prognosis of squamous cell carcinoma of
      the pyriform sinus, in spite of the combination of radical surgery and high dose
      postoperative radiotherapy.

PMID- 8554883
TI  - [Feasibility of retroperitoneal pelvic lymph node exploration in cancers of the
      cervix treated by radiosurgery association or radiotherapy alone. Apropos of a
      series of 52 cases].
AB  - From June 1980 to May 1993, 52 patients with a mean age of 49, underwent a
      retroperitoneal pelvic lymph node laparoscopic procedure for cervix carcinoma
      classified as stage IA (14), IB (12), IIA (6), IIB (14), IIIB (3), IVA (3). Two
      techniques were used: a retroperitoneoscopy in 16 cases and a panoramic
      retroperitoneal pelviscopy (PRPP) in 36 cases. The aim was to define, with a
      better accuracy, the pelvic lymph node status, to adapt the target volume, and to
      estimate the morbidity. More nodes were biopsied with PRPP than with
      retroperitoneoscopy (p < 0.05). There was a disagreement between the conventional
      radiologic assessment and the histological results in 28.6%. Specificity is 100%.
      Intra-operative and post-surgical morbidity was equivalent in the two procedures.
      One grade 3 urinary late morbidity (3%) was observed among the 33 patients who
      underwent a pelvic external irradiation. There was no morbidity of the gastro
      intestinal tract. Discussion deals with the support offered by the two
      laparoscopic procedures to define the pelvic lymph node status, to choose the
      planning target volume, and to precise the lymph node boost.

PMID- 8554884
TI  - [Pulse dose rate curietherapy].
AB  - The pulse dose rate (PDR) afterloading system is a new afterloading system which
      operates on the pulsed brachytherapy principle. A typical pulse length is 10
      minutes, increasing to approximately 30 minutes three months later as the iridium
      192 source decays. The pulse treatment is repeated each hour. The source activity
      is 1 Ci or less and thus the system can be installed in shielded rooms suitable
      for low dose rate implants. The PDR afterloading system enables equivalent
      continuous low dose rate treatments to be given with all the advantages of a
      stepping source: only one source to replace once every three months (no source
      inventory required), no source preparation, programmable low dose rate,
      optimization of dose distribution, radiation protection, patient can be
      disconnected between pulses, intracavitary, interstitial, intraoperative, and
      intralumenal treatments feasible using a single afterloader.

PMID- 8554885
TI  - [Is "pulse dose rate" curietherapy comparable to low dose rate brachytherapy?].

PMID- 8554886
TI  - [Permanent committee of European physicians, Brussels].

PMID- 8554887
TI  - [Activity of radiosurgery. The SFRO-1994 survey].

PMID- 8554888
TI  - [Inventory of low dose brachytherapy in anticancer centers. A survey of the
      radiotherapy group of the National Federation of anticancer centres].

PMID- 8554889
TI  - [Which equipment for proton therapy of the future?].
AB  - The success of proton therapy depends on its cost. Hospital based equipment in
      fabrication for the Massachusetts General Hospital in Boston costs in the excess
      of 17 millions dollars, the accelerator being only a fraction of the cost. We
      think that price can be significantly decreased. We review the different new ways
      of accelerating protons currently under study in France in order to build a
      smaller, less expensive but reliable treatment device.

PMID- 8554890
TI  - [The cost of radiotherapy. Evaluation of the real cost of treatments performed in
      a radiotherapy service of a center for fight against cancer].
AB  - The authors present a retrospective analysis dealing with the cost of therapeutic
      procedures achieved in the department of radiotherapy of the Centre Claudius
      Regaud. This analysis was performed according to the actual cost of the different
      components of each treatment including the human costs. For this last purpose,
      serial countings of time spent by each category of employees were performed and
      then translated into financial terms. Results show a large discrepancy between
      the costs of therapeutic procedures. These differences are mainly related to the
      purpose of therapeutic plan, dealing with the most expensive procedures dealing
      with the developmental treatments. This study provides a tool that can be used by
      medical and/or administrative managers of radiation oncology departments when
      changes or innovations in therapeutic procedures. This cost accounting analysis
      is compared to the French administrative procedures used to pay the health care
      services and to determine the level of hospital resources.

PMID- 8554891
TI  - [Contribution of a new technique of digital enhancement for the control of
      radiation fields].
AB  - To increase geometric treatment accuracy in radiation therapy, we used a novel
      digitized method and original image processing. The radiographic films that are
      conventionally used for verifying each beam during the treatment were digitized
      by a Kodak digital system and then an original image enhancement was applied. For
      the evaluation of our technique, a clinical trial with two tests was used. The
      trial involved four readers doing 80 reading. The enhanced films were judged to
      be of higher quality than the non enhanced films (p = 0.001) and were read more
      accurately (p < or = 0.001). This automatic enhancement of digitized captured
      portal images can be easily integrated into the busy routine of a radiotherapy
      department.

PMID- 8554892
TI  - Radiation therapy with or without surgery in the management of low-grade brain
      astrocytomas. A retrospective study of 120 patients.
AB  - From 1977 to 1988, 120 consecutive patients with a diagnosis of low-grade
      astrocytoma were referred to our department for radiotherapy. Fourty-one patients
      (group 1) underwent surgery and post operative external radiation therapy (2
      gross total resections and 39 subtotal resections). Sixty-nine patients underwent
      exclusive external radiotherapy (group 2). In ten patients, the irradiation was
      delivered by stereotactic implantation of iridium-192 wires into the tumor with
      or without external irradiation (group 3). Ten had pilocytic astrocytomas (mean
      age, 24 years) and twenty had microcystic astrocytomas (mean age, 35.4 years).
      The 5- and 10-year survival rates were 55.6% and 44.4%, respectively and 55% and
      48%. Ninety astrocytomas were classified as "ordinary" astrocytoma (mean age,
      36.8 years). The 5- and 10-year overall survival rates were 51% and 20.5%,
      respectively. The same probabilities at 5 and 10 years were 65% and 37%
      respectively, for group 1, 38.8% and 12.7% for group 2 and, 78.8 and 22.5% for
      group 3. In multivariate analysis, two prognostic factors had a significant
      impact on overall survival: IK score (IK < 90 vs IK > or = 90, p = 0.0001),
      surgical resection (surgical resection and post operative radiotherapy vs
      radiation therapy alone, p = 0.012). However, the patients who underwent surgical
      resection were those in the best condition, having tumors that were easily
      accessible and less invasive.

PMID- 8554893
TI  - [Contribution of radiotherapy in the treatment of carcinomas of the cavum in
      Yaounde].

PMID- 8554894
TI  - [Place of radiotherapy in carcinomas of the tonsil].

PMID- 8554895
TI  - [Focus on the activity of the European group of radiobiology. NCI TPOT study T92
      0045. 9 June 1995, Lyon].

PMID- 8554896
TI  - Analysis and localization of cyclophilin A found in the virions of human
      immunodeficiency virus type 1 MN strain.
AB  - Previous reports have shown that cyclophilin A (CyPA) is found to be specifically
      associated with human immunodeficiency virus type-1 (HIV-1) virions and is
      required for infectivity (Franke et al. Nature 372:359; Thali et al. Nature
      372:363). We have examined CyPA associated with HIV-1MN virions. Virions from
      infected human lymphoid cells were analyzed by high-pressure liquid
      chromatography (HPLC), protein sequence, and immunoblot analysis. At least three
      forms of CyPA were found: an unmodified form, an N-terminally modified form, and
      an N-terminally modified form that migrates as a larger isoform on a reducing-SDS
      polyacrylamide gel. Using a protease digestion procedure, CyPA that is associated
      with virions was found to be located inside the viral membrane. Similar
      examination of SIVMne produced by HUT-78 human T cells did not detect specific
      incorporation of CyPA into SIV virions. Our results are consistent with the role
      of CyPA acting early in the infectious process of HIV-1.

PMID- 8554897
TI  - HIV acquires functional adhesion receptors from host cells.
AB  - CD4 is known to serve as the principal cellular receptor for HIV. However,
      several observations suggest that other molecules may be involved in infection of
      cells by HIV. Cell adhesion molecules and their ligands expressed on HIV
      susceptible cells have been implicated in the biology of HIV in a number of
      studies. We have recently reported that HIV and SIV acquire cell adhesion
      molecules from host cells. We now report that a specific cell adhesion molecule,
      CD44, that is acquired by HIV retains its biological activity when expressed on
      the virus. We tested CEMx174 cells, which are CD4-positive and HIV-susceptible
      for phorbol ester-inducible binding to hyaluronic acid through CD44. Phorbol
      ester-stimulated but not unstimulated CEMx174 cells bound hyaluronic acid.
      Likewise, HIV from stimulated cells but not from unstimulated cells bound
      hyaluronic acid through acquired CD44 molecules. This is the first demonstration
      that adhesion molecules acquired by HIV are functional and the results imply that
      HIV may have the capacity to bind to any cell or substrate that its host cell
      binds to. The demonstration of functional adhesion receptors on HIV has important
      implications with respect to the tropism, infectivity, and dissemination of HIV.

PMID- 8554898
TI  - Enhanced susceptibility to human immunodeficiency virus infection in CD4+ T
      lymphocytes genetically deficient in CD43.
AB  - CD43 is a cell surface sialoglycoprotein expressed by most cells of hematopoietic
      origin, including all T lymphocytes. Elimination of CD43 expression by gene
      targeting in the CEM T cell line results in its increased homotypic adhesion and
      binding to HIV-1 gp120. Here we report that the CD43-negative CEM cells show
      increased susceptibility to HIV-1 infection and increased viral replication
      compared with the parental CD43+ CEM cell line. Increased HIV-1 replication also
      was observed in CEM cells with diminished CD43 expression secondary to functional
      inactivation of a single CD43 allele. The CD43- CEM cells were more susceptible
      to HIV-1-induced cytopathicity than their CD43+ counterparts. HIV-1 replication
      also was increased in the CD43- CEM cells after transfection with the infectious
      HIV molecular clone pNL4-3. These data suggest that factors that diminish CD43
      expression on T lymphocytes may enhance their susceptibility to HIV-1 infection.

PMID- 8554899
TI  - Kinetics of HIV infection of human placental syncytiotrophoblast cultures: an
      ultrastructural and immunocytochemical study.
AB  - We previously demonstrated that syncytiotrophoblast (ST) cells from term human
      placentas could be infected when cocultured with HIV-infected lymphocytic cells.
      Here, we have used fluorescence microscopy and transmission electron microscopy
      to examine the kinetics of this infection process. Molt-4 clone 8 cells infected
      with HIV-1Lai or filtered supernatant from these cultures were incubated with ST
      cells for different times. In cell-associated infection, immunofluorescence
      microscopy revealed that some ST colonies were positive for HIV core proteins
      (p24,p55) after 1 hr. The number of positive colonies and the intensity of the ST
      associated fluorescence increased with time. Transmission electron microscopy
      showed viral particles with HIV morphology associated with the ST cell surface at
      1 hr. Immature virions with budding morphology were observed at 2 hr. In cell
      free infection, positive p24,p55 staining was first detected in a few ST colonies
      at 4 hr. The number of positive colonies increased with time. At 24 hr, the
      fluorescence pattern and intensity resembled that seen with cell-mediated
      infection at 4 hr. Transmission electron microscopy revealed an increasing number
      of viral particles associated with the ST cell plasma membrane with respect to
      time, and budding virions first appeared at 8 hr. These results demonstrate that
      HIV infection of placental ST cells proceeds very rapidly in culture and that,
      furthermore, cell-associated infection of ST is much more efficient than the
      infection with cell-free virus.

PMID- 8554900
TI  - Suppression of HIV replication in human monocyte-derived macrophages induced by
      granulocyte/macrophage colony-stimulating factor.
AB  - Susceptibility to HIV infection was examined in macrophages differentiated from
      human monocytes by macrophage colony-stimulating factor (M-CSF) or
      granulocyte/macrophage colony-stimulating factor (GM-CSF). The replication of
      macrophage-tropic human immunodeficiency virus type-1 (HIV-1), which was
      determined by reverse transcriptase (RT) activity, was significantly suppressed
      in macrophages induced by GM-CSF (GM-type macrophages) but not in those induced
      by M-CSF (M-type macrophages). Multinucleated giant cells were formed only in M
      type macrophages after HIV infection. However, the expression of CD4 molecules on
      the surface of both types of macrophages was similar and the proviral DNA was
      detectable in cell lysates of both macrophages, although the amount of proviral
      DNA in M-type macrophages was higher than that in GM-type macrophages. Many steps
      have been defined in HIV infection and replication, such as adsorption of HIV to
      the cell surface, internalization of the viral core into the cytoplasm, uncoating
      of viral RNA, reverse transcription and integration of proviral DNA into cellular
      DNA, transcription and translation of proviral DNA, assembly of viral components,
      and budding of virus particles. Our findings suggested that the suppression of
      HIV-1 replication in macrophages induced by GM-CSF is mainly due to a disturbance
      at certain steps of replication after synthesis of the proviral DNA. Thus, the
      suppression of HIV replication in GM-type macrophages may provide a model of the
      latency of HIV infection in vivo.

PMID- 8554901
TI  - HIV type 1 extracellular Tat protein stimulates growth and protects cells of BK
      virus/tat transgenic mice from apoptosis.
AB  - Cells from BKV/tat transgenic mice were characterized for their tumorigenic
      phenotype in nude and syngeneic BDF mice. The results indicate that the BKV/tat
      recombinant transgene has a weak tumorigenic potential, mostly predisposing to
      oncogenesis, and that second events are required for the development of
      tumorigenicity. Tat is endogenously produced and released by tumor cells. It is
      taken up by recipient cells directly from the culture medium, without need of
      cell to cell contact. Extracellular Tat stimulates proliferation of cells from
      BKV/tat transgenic mice and protects them from apoptosis under conditions of
      serum starvation. Our results are in agreement with a model in which Tat induces
      its effects on target cells in two different ways. Growth promotion may require
      interaction of extracellular Tat with surface receptors eliciting a signal for
      cell proliferation, whereas intranuclear localization of Tat is necessary for
      transactivation of viral and cellular genes.

PMID- 8554902
TI  - Iron chelation decreases NF-kappa B and HIV type 1 activation due to oxidative
      stress.
AB  - An important aspect of human immunodeficiency virus (HIV-1) infection is the
      regulation of its expression by nuclear factor kappa B (NF-kappa B) through redox
      controlled signal transduction pathways. In this study, we demonstrate that iron
      chelation by deferoxamine (DFO) protects against the cytotoxic and reactivating
      effects of hydrogen peroxide (H2O2). These protective effects were observed both
      in lymphocytic (ACH-2) and promonocytic (U1) cells latently infected by HIV-1.
      Concomitantly, NF-kappa B activation by H2O2, when followed by gel retardation
      assay, was decreased in the DFO-treated U1 and ACH-2 cells. This latter DFO
      mediated effect was specific, as DFO did not clearly affect AP-1 DNA-binding
      activity when studied after H2O2-induced stress. More importantly, DFO protected
      against the H2O2-induced activation of HIV-1 as evidenced by reverse
      transcriptase activity in the supernatant. DFO also protected against PMA-induced
      NF-kappa B activation as well as TNF-alpha-induced HIV-1 activation. Furthermore,
      DFO attenuated the p24 response in PBMC infected with HIV-1 and stimulated with
      IL-2. These different effects of DFO were obtained at DFO concentrations lower
      than 5 microM. Other chemically unrelated iron chelators also provided protection
      against cytotoxicity, NF-kappa B activation, and HIV-1 activation in U1 cells
      challenged with H2O2.

PMID- 8554903
TI  - Intracellular trafficking of the human immunodeficiency virus type 1 Rev protein:
      involvement of continued rRNA synthesis in nuclear retention.
AB  - We have explored the mechanism directing the intracellular trafficking and
      nucleolar accumulation of the human immunodeficiency virus type 1 (HIV-1) Rev
      protein. Treatment of Rev-expressing cells with mycophenolic acid, an inhibitor
      of inosine monophosphate dehydrogenase, resulted in a redistribution of Rev from
      the nucleoli to the nucleoplasm and cytoplasm. In contrast, a Rev effector domain
      mutant was retained in the nucleus, indicating the involvement of this domain in
      the protein's nuclear retention/nucleocytoplasmic transport. Identical results
      were obtained by inhibiting transcription using actinomycin D or 5,6
      dichlorobenzimidazole riboside. All three drugs were found to inhibit
      biosynthetic labeling of ribosomal RNA and to disrupt nucleolar morphology,
      suggesting a correlation between nucleolar/nuclear retention of Rev, continued
      ribosomal RNA synthesis, and intact nucleolar architecture. Results of
      binding/immunofluorescence assays using isolated, permeabilized nuclei and
      extracts of cells expressing Rev demonstrated that the protein is able to bind to
      nucleoli in vitro, in the absence of active cellular processes or eukaryotic
      posttranslational modifications. Rev derived from actinomycin D-treated cells
      showed equivalent binding, indicating that the inhibitor did not directly
      interfere with the ability of the protein to interact with nucleolar structures.
      Rev's interaction with nucleoli was directed by the protein's arginine-rich RNA
      binding/nucleolar localization domain, and was abrogated by pretreatment of the
      nuclei with RNaseA, indicating a requirement for RNA, probably ribosomal RNA.

PMID- 8554904
TI  - Development of a human thymic organ culture model for the study of HIV
      pathogenesis.
AB  - The development of effective therapies for the treatment of AIDS would be
      facilitated by a better understanding of HIV pathogenesis in vivo. While some
      aspects of pathogenesis may be assessed by standard tissue culture assays, in
      vivo animal models may provide clues to other aspects of HIV-mediated progression
      toward AIDS. Current animal models include primate models for the study of simian
      immunodeficiency virus (SIV) and HIV, SCID-hu and hu-PBL SCID mouse models for
      the study of HIV, and feline models for the study of feline immunodeficiency
      virus (FIV). In general these models are costly and labor intensive. We have
      developed a simple human fetal thymic organ culture (TOC) system that is
      permissive for HIV infection and that exhibits pathology similar to that observed
      in vivo. A key feature of this system is the time-dependent destruction of
      thymocytes typified by the preferential loss of CD4-expressing cells. HIV
      mediated thymocyte destruction occurs by a process involving programmed cell
      death. We have infected TOC with a panel of HIV isolates and found that the
      resulting viral replicative and pathogenic profiles are similar to those seen in
      the SCID-hu Thy/Liv mouse, yet different from profiles observed in standard PHA
      blast tissue culture assays. In addition, we find that TOC may be used to assess
      efficacy of antiviral agents such as AZT (3'-azido-3'-deoxythymidine) and ddI
      (2',3'-dideoxyinosine) in blocking both viral replication and virus-induced
      pathology. These results indicate that this model is amenable to the systematic
      manipulation, analysis, and characterization of a variety of HIV virus isolates
      and antiviral therapies.

PMID- 8554905
TI  - Rapid molecular epidemiology of human immunodeficiency virus transmission.
AB  - Close sequence homology between strains of HIV-1 have been used to corroborate
      cases of epidemiologically identified transmission. As an alternative to
      extensive DNA sequence analysis, genetic relateness between pairs of HIV
      quasispecies was estimated using the reduced electrophoretic mobilities of HIV-1
      envelope DNA heteroduplexes through polyacrylamide gels. All six infections
      acquired in a dental practice in the late 1980s and four of six infections
      acquired through blood product transfusions and sexual contact in 1984-1985 could
      be rapidly identified. A rising level of genetic diversity within HIV-1 subtype B
      facilitated the detection of later transmission events. Transmission linkages
      could be detected up to 4 years following infection. The simple and rapid
      technique of DNA heteroduplex tracking can therefore assist epidemiological
      investigations of HIV transmission and potentially of other genetically variable
      infectious agents.

PMID- 8554906
TI  - Functional activities of 20 human immunodeficiency virus type 1 (HIV-1)-specific
      human monoclonal antibodies.
AB  - Antibodies that are useful in the treatment of HIV infection should result in
      virus neutralization or lysis of infected cells but should not enhance infection.
      In this study, the potential clinical use of 20 HIV-1-specific human monoclonal
      antibodies (HuMAbs) was determined by measuring their enhancing (C-ADE)
      activities using HIVLAI as the target virus. Two HuMAbs mediated both C-ADE and
      ADCC, two exclusively neutralized, and five exclusively mediated ADCC. Ten HuMAbs
      demonstrated no activity in any of the three assays. Three antibodies that
      neutralized HIVLAI were tested against HIVSF2; all three also neutralized HIVSF2.
      Four of five HuMAbs mediating ADCC against HIVLAI that were also tested against
      HIVSF2 had ADCC activity against HIVSF2. These results demonstrate that many
      HuMAbs have unique functions, allowing the separation of potentially beneficial
      and harmful activities. Combinations of HuMAbs with ADCC and neutralizing
      functions may have therapeutic utility.

PMID- 8554907
TI  - Alanine substitution of two arginines in amino terminus of V3 of SIV disrupts CD4
      binding whereas a similar replacement of two amino acids, lysine and arginine, in
      the carboxyl half of V3 prevents binding of a neutralizing monoclonal antibody.
AB  - A series of amino acid substitutions were carried out in the V3 loop of SIV gp120
      to investigate their effects on binding of the envelope to CD4 and neutralizing
      monoclonal antibodies. Alanine replacement of two adjacent arginines at the amino
      terminus of V3 resulted in a molecule that bound neither sCD4 nor conformation
      dependent neutralizing monoclonal KK5 and KK9. A similar substitution of two
      amino acids, lysine and arginine, in the carboxyl half of V3 disrupted binding to
      KK9 without affecting CD4 binding. Removal of V3 from the envelope gave rise to a
      molecule that was not secreted. These data suggest a close linkage between V3 and
      CD4 binding domains of gp120, although neutralizing antibodies directed to V3 do
      not block binding of gp120 to CD4. We propose that differences in the modes of
      interactions of the V3 disulfide loops with CD4 in SIV and HIV may be responsible
      for the observed different neutralizing properties of the two V3 loops.

PMID- 8554908
TI  - Involvement of gag- and env-specific cytotoxic T lymphocytes in protective
      immunity to feline immunodeficiency virus.
AB  - Definition of the immunological mechanisms involved in protective immunity
      against lentiviral infections is crucial to the development of an effective
      vaccine. The induction of gag- and env-specific cell-mediated immune responses
      was studied in cats following vaccination with whole inactivated feline
      immunodeficiency virus (FIV). Cats were immunized by inoculation with three doses
      of paraformaldehyde-inactivated FIV, derived from the feline lymphoid cell line,
      FL-4, which is persistently infected with the Petaluma isolate of FIV. Autologous
      or allogeneic skin fibroblasts either infected with recombinant FIV gag- or env
      vaccinia virus or pulsed with FIV env peptides were used as targets in chromium
      51 release assays. Effector cells were fresh peripheral blood mononuclear cells.
      Following the third immunization, all vaccinated cats, but none of the control
      cats immunized with adjuvant alone, had detectable FIV env-specific
      lymphocytotoxicity in their peripheral blood. Two cats also exhibited gag
      specific activity. There was no recognition of either allogeneic skin fibroblasts
      infected with recombinant vaccinia virus or autologous target cells infected with
      wild-type vaccinia virus, indicating the specificity and MHC-restricted nature of
      the response. Vaccinated cats, but not control cats, were protected from
      challenge with the homologous Petaluma isolate of FIV. Partial epitope mapping of
      the env-specific cytotoxic response was performed using overlapping 10-amino acid
      peptides from the env V3 domain of FIV. This response appeared to be directed at
      env peptide 1 (RAISSWKQRN) and env peptide 3 (QRNRWEWRPD), which lie adjacent to
      a beta-turn within the V3 domain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554909
TI  - HTLV-I activates complement leading to increased binding to complement receptor
      positive cells.
AB  - This investigation was performed to determine whether HTLV-I can activate
      complement, since previous studies show that complement activation by some
      viruses, including HIV-1, can enhance binding to, and infection of complement
      receptor-positive (CR+) cells. Complement treatment increased binding of HTLV-I
      to CR+ HPB-ALL cells by approximately 5-fold. In contrast, increased binding was
      not observed with H9 cells, which lack CR. Heat inactivation or EDTA treatment of
      complement blocked this increased binding while EGTA treatment only partially
      blocked binding. Anti-CR2 antibody significantly blocked binding of complement
      treated HTLV-I to HPB-ALL cells. Since previous studies showed that HIV-1 could
      activate complement, activation of complement by this virus was compared with
      HTLV-I. It was observed that binding of HTLV-I to HPB-ALL cells was enhanced by
      highly dilute complement (> or = 1:810) while HIV-1 required much higher
      concentrations of complement (> or = 1:30), indicating that HTLV-I is a much
      stronger complement activator. Treatment with complement transiently increased
      the ability of HTLV-I to infect CR+ cell lines as judged by provirus formation (4
      to 8-fold increase) and p24 production (5- to 10-fold increase). In contrast,
      complement treatment did not increase infection of CR- cells. In conclusion this
      study shows that HTLV-I activates complement leading to increased binding to, and
      transiently increased infection of, CR+ cells. This complement-mediated increased
      binding of HTLV-I may dramatically affect viral trafficking and immunological
      reactivity of virus in vivo.

PMID- 8554910
TI  - Characterization of a transcriptional attenuator within the 5' R region of the
      human T cell leukemia virus type 1.
AB  - Several regulatory sequences have been characterized in the HTLV-I promoter. We
      report here identification of a sequence element downstream of the
      transcriptional start site within the first 52 nucleotides of the 5' R region,
      which acts negatively on the activity of the HTLV-I promoter. Determination of
      the half-lives of the RNAs either including or lacking this sequence element
      showed that the observed effect intervenes at the transcriptional level. This
      negative element does not affect basal activity of the HTLV-I TATA box, but down
      regulates transcription induced by strong activators. Thus, we propose that this
      so-called negative regulatory sequence functions as an attenuator of
      transcription.

PMID- 8554911
TI  - Does the key to a successful HIV type 1 vaccine lie among the envelope sequences
      of infected individuals?

PMID- 8554912
TI  - Analysis of the V3 loop sequences from 10 HIV type 1-infected AIDS patients from
      Paraguay.

PMID- 8554913
TI  - Highly divergent env sequences of HIV-1 B subtype with two novel V3 loop motifs
      detected in an AIDS patient in Miami, Florida.

PMID- 8554915
TI  - Molecular characterization of an HIV type 1 isolate from Burundi.

PMID- 8554914
TI  - Sequence and phylogenetic analysis of glycoprotein 120 of an HIV type 1 variant
      (GWGR) prevalent in Brazil.

PMID- 8554916
TI  - Biological Therapy of Cancer--From Basic Research to Clinical Application, the
      3rd International Symposium. Munich, Germany, April 1995. Abstracts.

PMID- 8554917
TI  - Toward a more complete molecular description of the osteoclast.

PMID- 8554918
TI  - Osteoclast molecular phenotyping by random cDNA sequencing.
AB  - The osteoclast is a cell type that is highly specialized for its bone resorption
      function. In order to decipher the numerous biochemical functions of osteoclasts,
      a description of the gene expression profile of osteoclasts would be beneficial.
      We have sought to identify genes that are highly expressed in osteoclasts by
      partially sequencing 194 randomly chosen cDNA clones from a representative rabbit
      osteoclast cDNA library. Comparison to nucleic acid and protein sequence
      databases indicates that 135 of these cDNAs are identical to or homologous to
      known mammalian genes. Reverse transcription-polymerase chain reaction (RT-PCR)
      assays with microisolated osteoclasts were used to verify the osteoclast
      expression of some of these genes. Fifty-nine cDNAs, including two abundantly
      expressed species, have no significant similarity to the sequence databases and
      likely represent novel genes. The most abundant of the osteoclast expressed genes
      encode cofilin and the vacuolar H(+)-ATPase 16 kd subunit. Each were represented
      at a frequency of 4.1% of the clones in the library (95% confidence interval =
      2.4-6.6%). The high expression of these gene products is consistent with the high
      motility of osteoclasts and their very active hydrogen ion secretion. Other
      abundantly expressed sequences include beta-actin (95% C.I. = 2.0-6.0%), creatine
      kinase B (95% C.I. = 1.2-4.9%), c-fms and ribosomal protein L18 (95% C.I. = 0.8
      4.3%), and cathepsin-OC2, cyclophilin, delta-aminolevulinate synthetase, 16S
      mitochondrial rRNA, and two novel gene sequences (95% C.I. = 0.5-3.6%).

PMID- 8554919
TI  - Localization of the Ca(2+)-binding alpha-parvalbumin and its mRNA in epiphyseal
      plate cartilage and bone of growing rats.
AB  - This study describes the localization of alpha-parvalbumin, in undecalcified
      tibial epiphyseal cartilage and bone of growing rats by immunocytochemistry in
      the light microscope, and of parvalbumin mRNA by in situ hybridization. They were
      compared to the distribution of the calbindin-D9K and its mRNA in rat epiphyseal
      cartilage. All the chondrocytes of the epiphyseal cartilage were parvalbumin
      immunopositive, but there was no parvalbumin immunoreactivity in the uncalcified
      or calcified extracellular cartilage matrix. The intensity of the immunostaining
      increased from the resting and proliferative to the mature and hypertrophic
      chondrocytes, with the greatest intensity in the terminal hypertrophic
      chondrocytes in the calcifying zone. The parvalbumin immunostaining was located
      in the cytoplasm, but no immunoreactivity was detected in any chondrocyte
      processes. The parvalbumin mRNA distribution and levels, as revealed by in situ
      hybridization, exactly mirrored those of the parvalbumin protein. In contrast to
      parvalbumin, calbindin-D9K and its mRNA appeared in mature chondrocytes and
      decreased in hypertrophic up to calcifying chondrocytes. Calbindin-D9K was
      located in the cytoplasm and all along the cell processes. In bone, the
      osteoblasts and the osteocytes of trabecular and compact cortical bones were
      immunoreactive for parvalbumin and contained parvalbumin mRNA. Parvalbumin lay in
      their cytoplasm, but there was no parvalbumin immunostaining in the extracellular
      uncalcified or mineralized bone matrix. The long processes of osteocytes, in
      compact bone only, were parvalbumin immunoreactive. Osteoclasts contained
      cytoplasmic parvalbumin immunoreactivity. Thus, the pattern of immunoreactive
      parvalbumin distribution indicates that the protein is not involved in the
      extracellular mineralization of cartilage and bone matrix. It appears to be
      associated with specific calcium-related intracellular functions in chondrocytes
      and in osteoblasts, osteocytes, and osteoclasts. As the highest cytoplasmic
      concentration of parvalbumin is in the terminal hypertrophic chondrocytes,
      parvalbumin could act as a calcium buffer to delay the death of chondrocytes. In
      compact bone, parvalbumin could also have a role throughout the osteocyte
      processes in regulating the fluxes of calcium ions for mineral homeostatis.

PMID- 8554920
TI  - Genetic lineage, bone mass, and physical activity in mice.
AB  - Five strains of inbred mice were found to have variations in bone mass although
      they were similar in body weight. Two of these strains, C57BL/6J and A/J, were
      studied in greater detail and the former had more bone in both femur and tibia.
      The increased bone mass was associated with larger quadriceps muscles in the
      C57BL/6J animals when measured at 18 weeks of age. Activities of animals from
      these two strains were studied over 24 h periods using a cage with an ultrasonic
      movement detector and automatic counter. The C57BL/6J animals were more active
      than the A/J mice. The male C57BL/6J mice tended to have larger testicles and
      higher testosterone levels than the A/J animals, whereas the female A/J animals
      had larger ovaries and higher oestradiol levels. As both male and female C57BL/6J
      animals were more active, it was concluded that the sex hormone differences
      between the two strains was not responsible for either the changes in bone mass
      or physical activity. These findings indicate that in the mouse, activity is in
      part genetically determined. We have hypothesized that this, in turn, could
      affect muscle mass and secondarily, bone size and strength. If these results can
      be applied to humans, it would suggest that differences at birth between
      individuals are important for bone mass in later life and that muscle mass and
      activity are in part genetically influenced. If this was the case, then muscle
      mass and strength could be a factor in bone mass and one of the goals in
      prevention and treatment of osteoporosis should be directed toward preservation
      and/or augmentation of muscle strength.

PMID- 8554921
TI  - A possible mechanism of the specific action of bisphosphonates on osteoclasts:
      tiludronate preferentially affects polarized osteoclasts having ruffled borders.
AB  - The mechanism of action of tiludronate [(4-chlorophenyl)-thiomethylene
      bisphosphonate] on osteoclastic bone resorption was examined in mouse culture
      systems. Tiludronate did not inhibit the formation of osteoclast-like
      multinucleated cells (OCLs) induced by 1 alpha,25-dihydroxyvitamin D3 in
      cocultures of mouse osteoblastic cells and bone marrow cells. OCLs obtained from
      cocultures on collagen gel-coated dishes, treated with tiludronate, formed as
      many resorption pits on dentine slices as those obtained from the control
      cocultures. However, pit formation by OCLs was dose-dependently inhibited when
      tiludronate was added directly to the pit formation assay. Other bisphosphonates
      such as alendronate and etidronate dose-dependently inhibited pit formation
      according to the in vivo potencies of the respective bisphosphonates to inhibit
      bone resorption. However, they had no inhibitory effect on the recruitment of
      OCLs induced by 1 alpha,25-dihydroxyvitamin D3 in the cocultures. When OCLs were
      placed on dentine slices, they formed the ringed structure of F-actin-containing
      podosomes and ruffled borders (polarized OCLs) even in the presence of
      tiludronate. However, the actin rings in OCLs were disrupted by the addition of
      tiludronate soon after they began to resorb dentine. In contrast, OCLs placed on
      collagen gel formed neither actin rings nor ruffled borders (nonpolarized OCLs),
      and showed no response to tiludronate. OCLs formed from the spleen cells of
      osteosclerotic (oc/oc) mice developed the ringed structure of podosomes, but not
      ruffled borders, on dentine slices. The actin ring in the oc/oc spleen cell
      derived OCLs placed on dentine slices was not disrupted by the addition of
      tiludronate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554922
TI  - Detection of transcripts and binding sites for colony-stimulating factor-1 during
      bone development.
AB  - Colony-stimulating factor-1 (CSF-1), originally characterized as the growth
      factor for the cells of the mononuclear phagocytic system, has been shown to be
      essential for osteoclast formation. The aim of the present study was twofold: (i)
      to investigate the expression of transcripts encoding CSF-1; and (ii) to detect
      binding sites for CSF-1 during bone development. As a model, metatarsal rudiments
      from embryonic mice of different ages were used, an in vivo system allowing one
      to follow osteoclast formation. In 16-day-old embryos, proliferating osteoclast
      precursors are located on the outer surface of the rudiments. They differentiate
      subsequently to post-mitotic precursors. At 18 days, the precursors fuse and the
      mature osteoclasts invade the mineralized cartilage of the rudiments to excavate
      the future bone marrow cavity. Within this study, in situ hybridization on
      sections of whole paws from 17-day-old embryos revealed CSF-1 transcripts to be
      present in cells lining the outside of the midregion of the metatarsals. One day
      later, cells containing CSF-1 mRNA were found within the mineralized cartilage.
      The levels of transcripts encoding CSF-1 were further increased in the bone
      rudiments of newborn animals. Binding sites for CSF-1 on cells in close proximity
      of the metatarsals were detected at embryonic age 17 days, but not before. At
      this stage, cells binding CSF-1 were located on the periosteum of the midregion
      of the metatarsal rudiment. At 18 days, cells expressing high levels of CSF-1
      binding sites had invaded the mineralized cartilage.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8554923
TI  - Automatic-interactive measurement of resorption cavities in transiliac bone
      biopsies and correlation with deoxypyridinoline.
AB  - Measuring bone resorption accurately by histomorphometry of bone biopsies is a
      challenge. Several techniques have been proposed including the measurement of
      eroded surfaces and resorption depth, but they have not been compared between
      themselves nor with biochemical assessment of bone resorption. In addition, there
      is a need for a rapid method that could be used more routinely. We describe here
      an automatic interactive method using a color analyzer (Visiolab, BIOCOM, France)
      with a specific software for the evaluation of erosion depth, eroded volume,
      eroded surface, osteoclast number, and surface. Thirty transiliac undecalcified
      bone biopsies stained with Goldner's trichrome were used in this study, taken
      from subjects suffering from osteoporosis or primary hyperparathyroidism. At the
      time of the biopsy a 2 h fasting morning urine sample was collected for
      measurement by HPLC of total deoxypyridinoline, the most sensitive marker of bone
      resorption. There was a highly significant correlation between maximum erosion
      depth measured directly and the one calculated according to the count of eroded
      lamellae (E. F. Eriksen, et al. Metab Bone Dis Relat Res 5:243-252; 1984) (r =
      0.76; p = 0.0001). A significant correlation was found between urinary
      deoxypyridinoline and eroded volume/bone volume in cancellous and endocortical
      bone measured with the automatic interactive technique (r = 0.48; p = 0.007). In
      contrast, other histological indexes of bone resorption did not correlate with
      urinary deoxypyridinoline. The volume of resorption cavities appears to be the
      most valid index of bone resorption rate as it was correlated with the urinary
      excretion of total deoxypyridinoline.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554924
TI  - Comparison of different models for interpreting bone mineral density measurements
      using DXA and MRI technology.
AB  - Bone mineral density measurements using dual X-ray absorptiometry (DXA) are
      commonly expressed as areal density (g/cm2). However, areal BMD (BMDareal) is
      dependent on bone size and this can lead to erroneous interpretations of BMD
      values. We have previously presented a simple method for calculating apparent
      volumetric bone mineral density (BMDvol) using ancillary DXA-derived data. In the
      present study we tested the validity of our model using in vivo volumetric data
      obtained from magnetic resonance imaging (MRI) of lumbar vertebrae. BMDareal and
      BMDvol of L3 were measured from sixteen pairs of identical twins (24 men, 8
      women), aged 25-69 years. The dimensions of the lumbar vertebra L3 were measured
      from MR images and BMD values were corrected for these dimensions. The DXA
      derived apparent volumetric bone mineral density (BMDvol) correlated moderately
      with MRI-derived BMDs (r values from 0.665 to 0.822). In contrast to BMDareal,
      BMDvol and MRI-derived BMDs were not related to body size variables. All these
      volume-corrected BMDs diminished the erroneous effect of vertebral size on areal
      BMD. We conclude that the simple DXA-derived BMDvol can be used for normalization
      of bone mineral density values in subjects of different body sizes, and
      especially in growing children.

PMID- 8554925
TI  - The iron-binding protein ferritin is expressed in cells of the osteoblastic
      lineage in vitro and in vivo.
AB  - Ferritin, a metal-binding protein responsible for maintaining the bioavailability
      of iron, has been demonstrated in cells of the osteoblastic lineage. Messenger
      RNAs encoding the light and heavy chain subunits of ferritin were detected in ROS
      17/2.8, ROS 25/1, and UMR106 rat osteosarcoma cell lines, in fetal rat calvaria,
      and in primary cultures of rat calvarial osteoblast-like cells. In vivo, the
      expression of ferritin light-chain mRNA was observed in both active osteoblasts
      and in osteocytes. A 450-kD iron-binding protein was immunoprecipitated from ROS
      17/2.8 cells by an antiferritin antiserum. This protein comigrated with native
      ferritin, and could be dissociated into subunits comigrating with ferritin light
      and heavy chains. Addition of extracellular Fe59-transferrin to cultures of ROS
      17/2.8 cells resulted in the sequestration of the iron in intracellular ferritin.
      These observations demonstrate that cells of the osteoblastic lineage possess a
      functional ferritin-based iron uptake and storage system capable of regulating
      metal homeostasis in bone.

PMID- 8554926
TI  - Prediction of thoracic and lumbar vertebral body compressive strength:
      correlations with bone mineral density and vertebral region.
AB  - The bone density of thoracolumbar vertebral columns (T1 to L5) from 18
      individuals was measured using quantitative computed tomography and dual energy x
      ray absorptiometry. Three hundred six isolated vertebral bodies were tested in a
      materials test device to determine their compressive strength. Between T1 and L5
      the mean segmental increase in bone mineral content was 0.3 g, while the
      corresponding mean decrease in trabecular density was 4.7 HU. Midvertebral body
      cross-sectional area increased by an average of 46 mm2 per segment and the mean
      segmental increase in compressive strength was 0.17 kN. Compressive strength was
      significantly correlated with bone mineral density measured with dual energy x
      ray absorptiometry (r = 0.86). Vertebral trabecular density samples measured with
      quantitative computed tomography were poorly correlated with compressive strength
      (r = 0.28); however, this was improved when the trabecular density was multiplied
      by the midvertebral body cross-sectional area (r = 0.83). This study provides
      information concerning the relationships between density and mechanical
      properties of all thoracic and lumbar vertebral bodies across a wide age range.
      While the load-bearing capacity of the vertebral bodies is largely dependent on
      their geometry and bone density, this relationship has been only extensively
      tested for the lumbar spine. This study extends these observations over the
      lumbar and thoracic regions to provide a comprehensive analysis of the strength
      characteristics of each vertebral body. This is particularly important given the
      paucity of data on the thoracic spine where age-related vertebral fractures
      predominate. These data provide a basis for the development of models to predict
      the potential for thoracolumbar fractures in the elderly vertebral column.

PMID- 8554927
TI  - Translocation of protein kinase C isoenzymes by elevated extracellular Ca2+
      concentration in cells from a human giant cell tumor of bone.
AB  - In this study we investigated the protein kinase C isoenzymes expressed by human
      osteoclast-like cells harvested from a giant cell tumor of bone (GCT23 cells),
      and by freshly isolated rat osteoclasts. Immunoblotting analysis revealed that
      the -alpha, -delta, and -epsilon, PKC isoforms, but not the -beta isoenzyme, are
      expressed by GCT23 cells. Immunofluorescence studies demonstrated that PKC-alpha,
      -delta, and -epsilon are homogeneously expressed by both mononuclear and
      multinucleated GCT23 cells, as well as by rat osteoclasts. Similar to authentic
      osteoclasts, GCT23 cells responded to an increase of extracellular Ca2+
      concentration ([Ca2+]o) with a dose-dependent elevation of the cytosolic free
      Ca2+ concentration ([Ca2+]i). An increase of [Ca2+]o stimulated the translocation
      of PKC-alpha from the cytosolic to the particulate fraction, suggesting the
      involvement of this isoenzyme in the signal transduction mechanism prompted by
      stimulation of the [Ca2+]o sensing. By contrast, PKC-delta was not altered by
      exposure to elevated [Ca2+]o, whereas PKC-epsilon underwent reciprocal
      translocation, disappearing from the insoluble fraction and increasing in the
      cytosol. The effects of PKC on GCT23 cell functions were investigated by
      treatment with phorbol 12-myristate, 13-acetate (PMA). We observed that
      activation of PKC by PMA failed to affect adhesion onto the substrate, but down
      regulated the [Ca2+]o-induced [Ca2+]i increases. The latter effect was specific,
      since it was reversed by treatment with the PKC inhibitors staurosporine and
      chelerythrine.

PMID- 8554928
TI  - The 5-lipoxygenase inhibitor BWA4C impairs osteoclastic resorption in a
      synchronized model of bone remodeling.
AB  - The role of leukotrienes on bone resorption was tested in a well-standardized
      model of bone remodeling by inhibiting their biosynthesis with BWA4C, a specific
      inhibitor of 5-lipoxygenase. After extraction of their upper molars unilaterally,
      30 Wistar rats were divided into three groups; the first remained untreated
      (control group), the second received 80 mg/kg/day of BWA4C dissolved in
      polyethylene glycol 300 (experimental group), and the third received only the
      vehicle (sham-treated group). After four days of experiment, the animals were
      killed and the resorption profile was assessed along the antagonist mandibular
      buccal cortex. The main result was a dramatic decrease in the number of TRAP
      positive mononucleated preosteoclasts in the experimental group (-69%, p < 0.0005
      and p < 0.003 vs. the control and sham-treated groups, respectively). This drop
      was related to a significant decrease in the number of osteoclasts. Neither the
      activation of the differentiated osteoclasts nor their mean interface with the
      bone surface were affected by BWA4C. Concomitantly, the mast cell population
      residing near the vascular network limiting the periosteum was markedly and
      significantly increased by the treatment. These mast cells were mostly
      degranulating, i.e., were in a state of activation that we previously found to
      related to resorption. These data suggest (1) that the leukotrienes are involved
      in the recruitment of osteoclast progenitors, and/or their differentiation into
      preosteoclasts, and (2) that mast cells responded to leukotriene
      inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554929
TI  - Method specificity of non-invasive blood pressure measurement: oscillometry and
      finger pulse pressure vs acoustic methods.
AB  - 1. The agreement of blood pressure measurements by stethoscope auscultation
      (SBPa, DBPa-IV and DBPa-V), oscillometry (Dinamap; SBPo, and DBPo) and digital
      photoplethysmography (Finapres; SBPf, and DBPf) with the graphical analysis of
      the analogue microphone signals of vascular wall motion sound (SBPg and DBPg) was
      evaluated in eight healthy subjects in the presence of responses to the
      intravenous infusion of 1 microgram min-1 isoprenaline. 2. In general, there was
      good agreement between the SBP/DBP-measurements based on auscultatory Korotkoff-I
      and IV-criteria and the reference method; the average method difference in
      estimating the isoprenaline responses for SBPa-SBPg was: -1.1, 95% CI: -5.4 to
      3.1 mm Hg with a within-subject between-method repeatability coefficient (REP) of
      11.6 mm Hg and for DBPa-IV-DBPg: 3.5, 95% CI: -0.5 to 6.5 mm Hg, REP: 11.5 mm Hg.
      The ausculatation of Korotkoff-V substantially overestimated the isoprenaline
      induced reduction of DBP: method difference DBPa-V-DBPg: -11.3, 95% CI: -17.8 to 
      4.7 mm Hg, REP: 31.8 mm Hg. 3. Oscillometry yielded good approximations for the
      SBP response to isoprenaline (average method difference SBPo-SBPg: -2.9, 95% CI: 
      9.0 to 3.3 mm Hg, REP: 17.6 mm Hg) but was poorly sensitive with regard to the
      DBP responses: method difference DBPo-DBPg: 6.5, 95% CI: -1.3 to 14.3 mm Hg, REP:
      25.7 mm Hg. 4. Whilst the finger pulse pressure agreed well with regard to DBP
      (method difference for the DBP responses to isoprenaline: DBPf-DBPg: 1.8, 95% CI:
      -5.1 to 8.6 mm Hg, REP: 18.5 mm Hg) it was rather unsatisfactory with regard to
      SBP (method difference SBPf-SBPg: -14.1, 95% CI: -28.2 to -0.1 mm Hg, REP: 49.9
      mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554930
TI  - Influence of basal nitric oxide secretion on cardiac function in man.
AB  - 1. Nitric oxide is recognised as an important biological mediator, which is
      thought to be involved in cardiovascular homeostasis. The purpose of this study
      was to investigate the effects of basal nitric oxide synthesis on cardiac
      function in man, by blocking nitric oxide synthesis with NG-monomethyl-L-arginine
      (L-NMMA). 2. Eight normal volunteers were studied on two separate occasions.
      Measurements of heart rate, blood pressure and echocardiographic indices of left
      ventricular systolic and diastolic function were made at baseline on each day and
      every 20 min during incremental infusion of L-NMMA (0.1, 0.2, 0.5, 1.0 and 2.0 mg
      kg-1 h-1) or placebo. 3. A trend towards reduction in heart rate was observed
      with L-NMMA infusion although this did not reach statistical significance,
      whereas significant increases in both systolic blood pressure (at 2.0 mg kg-1 h
      1) and systemic vascular resistance index (at 0.5 mg kg-1 h-1) were seen. 4. L
      NMMA infusion caused significant reductions in stroke distance and cardiac index,
      although there was no change in the ratio of end systolic wall stress/end
      systolic volume index (an afterload independent index of left ventricular
      systolic performance). 5. The isovolumic relaxation time significantly increased
      with L-NMMA infusion, together with a significant reduction in the 'E' wave flow
      velocity integral. Reductions in both peak E/A ratio and E/A flow velocity
      integral ratio were also seen, although these failed to reach statistical
      significance. 6. In conclusion, the basal generation of nitric oxide in man
      appears to maintain a vasodilated state, and modifies left ventricular diastolic
      filling parameters.

PMID- 8554931
TI  - An investigation into the direct and indirect venoconstrictor effects of
      endothelin-1 and big endothelin-1 in man.
AB  - 1. Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide that is
      generated through cleavage of its precursor big endothelin-1 by 'endothelin
      converting enzyme' (ECE) in resistance vessels, including those of the forearm
      vascular bed. In some animal tissues, but not in resistance vessels of healthy
      human subjects, endothelin-1 appears to potentiate the actions of the sympathetic
      nervous system. We examined whether ECE activity is present in human hand veins
      and whether endothelin-1 or big endothelin-1 potentiate sympathetically mediated
      venoconstriction. 2. Six healthy subjects received dorsal hand vein infusion of
      local, non-systemic doses of endothelin-1 (5 pmol min-1), big endothelin-1 (50
      pmol min-1) and, as a control, sodium chloride (0.9%; w/v) for 90 min. Vein
      diameter was measured using the Aellig displacement technique. Sympathetically
      mediated venoconstriction was elicited using the single deep breath reflex. 3.
      Endothelin-1 caused a progressive decrease in hand vein diameter, by 49% at 90
      min (95% confidence intervals [CI]: -68 to -30%; P = 0.0001). Vein diameter did
      not change significantly after 90 min infusion of big endothelin-1 (+3%; CI: -11
      to +17%; P = 0.0007 vs endothelin-1; P = 0.40 vs baseline) or sodium chloride
      (+2%; CI: -12 to +16%; P = 0.0002 vs endothelin-1; P = 0.60 vs baseline).
      Venoconstriction to deep breath was not potentiated by endothelin-1. 4. These
      results suggest that, in contrast to the situation in forearm resistance vessels,
      there is little or no local ECE activity in human hand veins and that endothelin
      does not potentiate sympathetic responses in these cutaneous capacitance vessels.

PMID- 8554932
TI  - Cardiopulmonary interactions of salbutamol and hypoxaemia in healthy young
      volunteers.
AB  - 1. Nebulised salbutamol is frequently used in the treatment of asthma and chronic
      obstructive pulmonary disease. Its effects on the cardiovascular system have been
      extensively investigated although as yet little is known concerning its effects
      on the pulmonary circulation, particularly during hypoxaemia. We have therefore
      examined the effects of nebulised salbutamol on pulmonary haemodynamics to see if
      it modifies hypoxic pulmonary vasoconstriction. 2. Eight healthy normal
      volunteers were studied on two separate occasions. After resting to achieve
      baseline haemodynamics patients were randomised to receive 5 mg salbutamol or
      placebo via a nebuliser. They were restudied after 30 min and then rendered
      hypoxaemic by breathing an N2/O2 mixture to achieve an SaO2 of 75-80%. Doppler
      echocardiography was used to measure mean pulmonary artery pressure (MPAP),
      cardiac output (CO) and hence pulmonary vascular resistance (PVR). 3. Treatment
      with salbutamol significantly increased MPAP during normoxaemia and hypoxaemia
      compared with placebo at 12.0 +/- 1.2 vs 8.0 +/- 0.7 mm Hg and 28.6 +/- 0.9 vs
      25.2 +/- 1.0 mm Hg, respectively (P < 0.05). Salbutamol caused a significant
      increase in heart rate compared with placebo and effects were additive to those
      of hypoxia at 74 +/- 2 vs 67 +/- 3 beats min-1 during normoxaemia and 84 +/- 3 vs
      77 +/- 4 beats min-1 during hypoxaemia, respectively (P < 0.05). Whilst systemic
      vascular resistance fell in response to salbutamol, PVR was unchanged by
      salbutamol during either normoxaemia or hypoxaemia. Cardiac output was increased
      by salbutamol and by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554933
TI  - Plasma concentrations and effects of salbutamol administered orally to patients
      with cystic fibrosis.
AB  - 1. To test whether cystic fibrosis (CF) altered the kinetics and dynamics of oral
      salbutamol, 11 patients with CF (19-33 years old; five females; FEV1: 37 +/- 12%
      of predicted value) and 10 healthy volunteers (20-41 years old; five females;
      FEV1: 99 +/- 14% of predicted value) received orally 4 mg salbutamol. 2. The
      estimated pharmacokinetic parameters of salbutamol in patients with CF were
      identical to those in healthy subjects. For instance, peak plasma concentrations
      of salbutamol were 10.5 +/- 2.6 (mean +/- s.d.) and 10.2 +/- 2.9 ng ml-1 (NS),
      and the area under salbutamol plasma concentrations as a function of time (AUC
      (0, 7 h)) was 43.0 +/- 9.3 ng ml-1 h and 43.3 +/- 12.7 ng ml-1 h (NS) in CF
      patients and in healthy subjects, respectively. Since on a mg kg-1 dose basis, CF
      patients received a dose 28% greater than healthy subjects, this lack of
      differences implies a decrease in the amount of salbutamol absorbed, or
      alternatively, an increase in both clearance and volume of distribution of
      salbutamol. 3. Salbutamol did not elicit bronchodilation in CF patients, but
      increased heart rate from 77 +/- 2 to 103 +/- 3 beats min-1 (P < 0.05). 4.
      Salbutamol decreased plasma potassium concentrations from 4.5 +/- 0.1 to 3.8 +/-
      0.1 mmol l-1 in the CF group (P < 0.05) and from 4.1 +/- 0.2 to 3.4 +/- 0.1 mmol
      l-1 in the controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8554934
TI  - Age and gender related changes in stereoselective pharmacokinetics and
      pharmacodynamics of verapamil and norverapamil.
AB  - 1. Pharmacokinetics and pharmacodynamics of R- and S-verapamil and R- and S
      norverapamil were studied at steady state following administration of 180 mg
      verapamil delivered by a controlled-release gastrointestinal therapeutic system
      (COER-verapamil). 2. Of the 30 young (19 to 43 years) and 30 elderly subjects (65
      to 80 years) enrolled, approximately half of each age group were women; all
      subjects were healthy and none were smokers. 3. Mean R- and S-verapamil and R-
      and S-norverapamil Cmax, Cmin, and AUC values for elderly subjects were 1.2 to
      2.2 times greater than those for young subjects; these differences were
      statistically significant at P < 0.05. Median tmax values for young and elderly
      subjects were not significantly different for any enantiomer. The mean half-life
      values of R- and S-verapamil for elderly subjects were approximately 20 h
      compared with approximately 13 h for young subjects, respectively. The mean half
      life values of R- and S-norverapamil for elderly subjects were approximately 31 h
      and 20 h, respectively, compared with approximately 19 h and 21 h for young
      subjects, respectively. 4. In both age groups, the mean plasma verapamil
      concentrations of each enantiomer were higher for women than for men at all time
      points. 5. Mean arterial pressure (MAP) had a significant correlation to R- (r2 =
      0.86) and S-verapamil (r2 = 0.87) concentration values that was not influenced by
      either gender or age of the patient. Change in PR-interval also had a significant
      correlation to R- and S-verapamil concentration values. However, the sensitivity
      of the response to changes in R- and S-verapamil concentration values in elderly
      subjects was about 1/5 of that in younger subjects.

PMID- 8554935
TI  - An in vitro technique for the rapid determination of drug entry into breast milk.
AB  - 1. A simple in vitro technique that predicts drug transfer into breast milk is
      described. 2. Drugs of differing physical and chemical characteristics were
      tested. 3. The technique provides an experimental system for studying plasma to
      milk transfer with changing milk composition. 4. A mechanism proposing a role of
      milk proteins in controlling drug entry into milk is discussed.

PMID- 8554936
TI  - Effects of flurbiprofen enantiomers on pain-related chemo-somatosensory evoked
      potentials in human subjects.
AB  - 1. The aim of the study was to investigate the analgesic effects of flurbiprofen
      enantiomers using an experimental pain model based on both chemo-somatosensory
      event-related potentials (CSSERP) and subjective pain ratings. 2. Healthy female
      volunteers (n = 16, age 23-36 years) participated in a placebo-controlled,
      randomised, double-blind, four-way crossover study. Single doses of (S)
      flurbiprofen (50 mg), (R)-flurbiprofen (50 and 100 mg) and placebo were
      administered orally. Measurements were taken before and 2 h after administration
      of the medications. During each measurement, 32 painful stimuli of gaseous carbon
      dioxide (200 ms duration, interval approximately 30 s) of two concentrations (60
      and 65% CO2 v/v) were applied to the right nostril. EEG was recorded from five
      positions and CSSERP were obtained in response to the painful CO2- stimuli.
      Additionally, subjects rated the perceived intensity of the painful stimuli by
      means of a visual analogue scale (VAS). 3. The CSSERP-amplitude P2, a measure of
      analgesic effect, decreased after administration of both (R)- and (S)
      flurbiprofen, while it increased after placebo. This was statistically
      significant at recording positions C4 (P < 0.01) and Fz (P < 0.05). The analgesia
      related decreases in evoked potential produced by (R)-flurbiprofen were dose
      dependent. Comparing similar doses of (R)- and (S)-flurbiprofen, the decrease in
      CSSERP-amplitudes produced by the (S)-enantiomer was somewhat more pronounced,
      indicating a higher analgesic potency. 4. The present data indicate that both
      enantiomers of flurbiprofen produce analgesic effects. Since (R)-flurbiprofen
      caused only little toxicity in rats as compared with the (S)-enantiomer or the
      racemic compound, a reduction of the quantitatively most important side effects
      in the gastrointestinal tract might be achieved by employing (R)-flurbiprofen in
      pain therapy.

PMID- 8554937
TI  - The pharmacokinetics of 8-methoxypsoralen following i.v. administration in
      humans.
AB  - 1. 8-methoxypsoralen (8-MOP) is a naturally occurring photoreactive substance
      which, in the presence of u.v. light, forms covalent adducts with pyrimidine
      bases in nucleic acids. For many years, 8-MOP has been used in PUVA therapy for
      treatment of psoriasis. Recently, the drug has been found to inactivate
      effectively bacteria spiked into platelet concentrates. The purpose of this study
      was to determine the pharmacokinetics and safety of 8-MOP administered
      intravenously in the bactericidal dosage range. 2. Eighteen volunteers were
      divided into three treatment groups to receive, respectively, 5, 10, and 15 mg 8
      MOP infused over 60 min. Frequent arterial samples were gathered, and the blood
      and plasma were assayed for 8-MOP concentration. The pharmacokinetic parameters
      were determined by moment and compartmental population analysis, the latter
      performed with the program NONMEM. Haemodynamics, ventilatory pattern, and
      subjective effects were recorded throughout the study. 3. The intravenously
      administered 8-MOP was well tolerated in all individuals, and no acute toxicity
      was observed. 4. The pharmacokinetics of 8-MOP were best described by a three
      compartment mammillary model in which the volumes and clearances were
      proportional to weight. The mean pharmacokinetic parameters for the plasma
      concentrations were: V1 = 0.045 1 kg-1, V2 = 0.57 1 kg-1, V3 = 0.15 1 kg-1, CL1
      (systemic) = 0.010 1 kg-1 min-1, CL2 = 0.0067 1 kg-1 min-1, CL3 = 0.012 1 kg-1
      min-1. The mean pharmacokinetic parameters for the blood concentrations were: V1
      = 0.061 1 kg-1, V2 = 1.15 1 kg-1, V3 = 0.21 1 kg-1, CL1 (systemic) = 0.015 1 kg-1
      min-1, CL2 = 0.011 1 kg-1 min-1 and CL3 = 0.015 1 kg-1 min-1. 5. The plasma
      pharmacokinetic model described the observations with a median absolute error of
      17%, and the blood pharmacokinetic model described the observations with a median
      absolute error of 18%. Analysis of the relative concentration of 8-MOP between
      plasma and red blood cells suggested concentration-dependent partitioning. 6. The
      addition of 7.5 mg 8-MOP to 300 ml platelet concentrate would produce
      bactericidal concentrations of 25 micrograms ml-1. Simulations based upon our
      data show that intravenous administration of 7.5 mg over 60 min would result in
      systemic concentrations of 8-MOP similar to those observed with conventional PUVA
      therapy. We conclude that the extensive safety history established in PUVA
      therapy will be applicable to this new application of 8-MOP.

PMID- 8554938
TI  - An unequal cross-over event within the CYP2D gene cluster generates a chimeric
      CYP2D7/CYP2D6 gene which is associated with the poor metabolizer phenotype.
AB  - 1. The study of the CYP2D genotype and phenotype of a Caucasian family revealed
      that a XbaI-9 kb allele was associated with the poor metabolizer phenotype. 2. A
      Polymerase Chain Reaction (PCR)-based assay showed that the previously described
      mutations D6A and D6B are not associated with the XbaI-9 kb allele. 3. To explore
      the molecular basis of the poor metabolizer phenotype associated with the XbaI-9
      kb allele, complete sequencing of the nine exons and intron-exon boundaries of
      the CYP2D6 gene was undertaken after amplification by PCR. 4. All the exons were
      successfully amplified using CYP2D6 gene-specific primers except exon 1 which
      required a combination of CYP2D7 gene-specific 5' primer and a CYP2D6 gene
      specific 3' primer. 5. Sequence data derived from this amplified product revealed
      that the XbaI-9 kb allele corresponds to a novel rearrangement of the locus. This
      involved a deletion of an approximately 20 kilobase (kb) DNA segment generating a
      hybrid 5' CYP2D7/CYP2D6 3' gene. 6. The chimeric gene is non-functional
      presumably due to an insertion in exon 1 (characteristic of the exon 1 of the
      CYP2D7 gene) which causes a shift in the reading frame with premature termination
      of translation.

PMID- 8554940
TI  - Detection of autoantibodies directed against human hepatic endoplasmic reticulum
      in sera from patients with halothane-associated hepatitis.
AB  - 1. Previous studies have demonstrated the presence of antibodies to
      trifluoroacetylated hepatic proteins (TFA-proteins) in sera from patients with
      the severe form of halothane-associated hepatitis (halothane hepatitis). The TFA
      proteins are produced via cytochrome P450-mediated metabolism of halothane to the
      reactive species TFA-chloride. 2. To investigate the presence of autoantibodies
      (which recognize various non-TFA-modified human hepatic polypeptides) in patients
      with halothane hepatitis immunoblotting experiments were performed using
      microsomal fractions prepared freshly from livers of five different (halothane
      free) tissue donors. Blots were developed using 15 well-characterised sera from
      patients with halothane hepatitis. 3. Autoantibodies to human hepatic
      polypeptides were detected in most, but not all, of the patients' sera. The
      pattern of antibody reactivity varied markedly between sera. Although no common
      pattern of antibody recognition was observed, polypeptides of molecular mass
      between 60 and 80 kDa were the predominant targets. A similar protein recognition
      pattern was seen when each positive serum was tested against the five individual
      human liver samples. 4. Such autoantibodies were not detected in sera from 16
      normal human blood donors, but were detected in three of six sera from patients
      exposed to halothane without developing hepatitis. 5. The autoantibodies are
      thought to arise in patients exposed to halothane as a consequence of a halothane
      induced immune response to chemically-modified proteins. Such antibodies could
      contribute to the complex pathological processes involved in halothane hepatitis.

PMID- 8554939
TI  - An investigation of the interaction between halofantrine, CYP2D6 and CYP3A4:
      studies with human liver microsomes and heterologous enzyme expression systems.
AB  - 1. We have assessed the interaction of the antimalarial halofantrine with
      cytochrome P450 (CYP) enzymes in vitro, with the use of microsomes from human
      liver and recombinant cell lines. 2. Rac-halofantrine was a potent inhibitor
      (IC50 = 1.06 microM, Ki = 4.3 microM) of the 1-hydroxylation of bufuralol, a
      marker for CYP2D6 activity. Of a group of structurally related antimalarials
      tested, only quinidine (IC50 = 0.04 microM) was more potent. 3. Microsomes
      prepared from recombinant CYP2D6 and CYP3A4 cell lines were shown to catalyse
      halofantrine N-debutylation. 4. The metabolism of halofantrine to its N-desbutyl
      metabolite by human liver microsomes showed no correlation with CYP2D6 genotypic
      or phenotypic status and there was no consistent inhibition by quinidine. 5. The
      rate of halofantrine metabolism showed a significant correlation with both CYP3A4
      protein levels (r = 0.88, P = 0.01) and the rate of felodipine metabolism (r =
      0.86, P = 0.013), a marker substrate for CYP3A4 activity. Inhibition studies
      showed that ketoconazole is a potent inhibitor of halofantrine metabolism (IC50 =
      1.57 microM). 6. In conclusion, we have demonstrated that halofantrine is a
      potent inhibitor of CYP2D6 in vitro and can also be metabolised by the enzyme.
      However, in human liver microsomes it appears to be metabolised largely by
      CYP3A4.

PMID- 8554941
TI  - Inter-individual and intra-individual variability of ethanol concentration-time
      profiles: comparison of ethanol ingestion before or after an evening meal.
AB  - 1. The magnitude of the variability of ethanol absorption is an important factor
      for studies that seek to determine the significance of potential interactions
      between ethanol and drugs. The aim of this study was to determine the extent of
      inter- and intra-individual variability of ethanol concentration-time profiles in
      fasted and fed subjects. 2. Twenty-four healthy male subjects were randomized to
      receive ethanol 0.3 g kg-1 before an evening meal on two study days and ethanol
      0.3 g kg-1 after an evening meal on two study days. Plasma ethanol concentrations
      were measured at intervals from 0-240 min. 3. There were significant differences
      in the mean area under the ethanol concentration-time curve (AUC), the mean peak
      ethanol concentration (Cmax), the mean ethanol elimination slope and the time to
      peak ethanol concentration between the fed and fasted subjects. There were no
      significant differences between the first and second study days for either fed or
      fasting subjects for all parameters. 4. There was no statistically significant
      difference in inter- or intra-subject variance between fed and fasted studies
      although the coefficients of variation (standard deviation expressed as a
      percentage of the mean) for the differences between the first and second study
      day were higher for fed studies. 5. The large inter- and intra-individual
      variability of alcohol absorption for both fasted and fed subjects must be
      considered in the design of alcohol-drug interaction studies.

PMID- 8554942
TI  - Evaluation of the central effects of alcohol and caffeine interaction.
AB  - 1. The dynamic and kinetic interactions of alcohol and caffeine were studied in a
      double-blind, placebo controlled, cross-over trial. Treatments were administered
      to eight healthy subjects in four experimental sessions, leaving a 1 week wash
      out period between each, as follows: 1) placebo, 2) alcohol (0.8 g kg-1), 3)
      caffeine (400 mg) and 4) alcohol (0.8 g kg-1) + caffeine (400 mg). 2. Evaluations
      were performed by means of: 1) objective measures: a) psychomotor performance
      (critical flicker fusion frequency, simple reaction time and tapping test), b)
      long latency visual evoked potentials ('pattern reversal'); 2) subjective self
      rated scales (visual analogue scales and profile of mood states); 3) caffeine and
      alcohol plasma concentration determinations. 3. The battery of pharmacodynamic
      tests was conducted at baseline and at +0.5 h, +1.5 h, +2.5 h, +4 h and +6 h. An
      analysis of variance was applied to the results, accepting a P < 0.05 as
      significant. The plasma-time curves for caffeine and alcohol were analysed by
      means of model-independent methods. 4. Results obtained with caffeine in the
      objective measures demonstrated a decrease in simple reaction time and an
      increase in the amplitude of the evoked potentials; the subjects' self-ratings
      showed a tendency to be more active. Alcohol increased simple reaction time and
      decreased amplitude of the evoked potentials, although the subjects rated
      themselves as being active. The combination of alcohol + caffeine showed no
      significant difference from placebo in the objective tests; nevertheless, the
      subjective feeling of drunkenness remained. The area under the curve (AUC) for
      caffeine was significantly higher when administered with alcohol.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8554943
TI  - Lack of effect of a 5-HT3 antagonist, pancopride, on lower oesophageal sphincter
      pressure in volunteers.
AB  - Effects of pancopride (5 and 10 mg, intravenously), on lower oesophageal
      sphincter pressure (LOESP), were assessed in healthy volunteers by means of
      oesophageal manometry. After pancopride 10 mg, the LOESP was higher than placebo
      and 5 mg pancopride but there were no differences among the three treatments (P =
      0.42). The areas under the curve were similar without differences, neither with
      absolute measurements (P = 0.53) nor after a baseline correction (P = 0.16). In
      conclusion, pancopride has no clinically relevant effect on lower oesophageal
      sphincter pressure.

PMID- 8554944
TI  - The effect of selegiline on the peripheral pharmacokinetics of levodopa in young
      volunteers.
AB  - The plasma pharmacokinetics of levodopa were studied in eight healthy young
      subjects following an i.v. infusion of 50 mg over 5 min. Subjects were studied on
      two occasions in random order following treatment with carbidopa; on one occasion
      they were pretreated with selegiline (four doses of 10 mg over the preceding 3
      days) and on the other with a placebo. The mean plasma concentration-time curves
      on each occasion were essentially superimposable and there were no significant
      differences in any calculated pharmacokinetic parameter. Selegiline does not
      significantly alter the distribution or elimination of levodopa from plasma.

PMID- 8554945
TI  - Modelling the market uptake of new drugs following listing for subsidy in
      Australia. A report from the Drug Utilisation Subcommittee of the Australian
      Pharmaceutical Benefits Advisory Committee.
AB  - The market uptake of five drugs following subsidy listing in Australia during the
      period 1990 to 1992 has been modelled using the sigmoid Emax model for drug
      receptor binding. Utilisation trends for simvastatin, omeprazole, budesonide,
      fluoxetine and moclobemide in defined daily dose (DDD) per 1000 population per
      day were smoothed by expressing as rolling annual averages. The results indicate
      good fits of the model to the data except for omeprazole, with good estimates of
      uptake rate and eventual maximum utilisation. Substantial differences between the
      drugs occurred in uptake rate which may be related to public education campaigns
      on asthma and coronary heart disease occurring during the release period. The
      very slow uptake of omeprazole relative to other drugs is likely to be due to
      restrictions on subsidised use. Modelling the market uptake rate and eventual
      utilisation of new drugs is useful as an aid to regulatory, quality use of
      medicines and financial decisions and allows comparisons between drugs to
      investigate factors important in market uptake.

PMID- 8554946
TI  - Omeprazole does not affect measured CYP3A4 activity using the erythromycin breath
      test.

PMID- 8554947
TI  - Calcium antagonists: when the content does not justify the headline.

PMID- 8554948
TI  - The importance of accuracy in blood pressure recording.

PMID- 8554949
TI  - Fat arms, obesity and choice of blood pressure cuff size in diabetic patients.
AB  - Four hundred consecutive diabetic patients had their mid-arm circumference (AC)
      measured and body mass index (BMI) calculated to determine the proportion of an
      unselected clinic group who would require a larger than standard adult blood
      pressure (BP) cuff and whether or not BMI could be used to predict AC and hence
      choice of appropriate BP cuff size. More than 75% of both men and women had an AC
      > or = 29cm, justifying a larger than standard adult cuff for their BP
      measurement. When patients were classified according to their BMI, at least 80%
      with a BMI > or = 30 and more than 70% with a BMI of 25-29 had a measured AC > or
      = 29cm, while less than a third of patients with a BMI > or = 25 had an AC > or =
      29cm. These results indicate that, in a diabetic clinic, most patients with a BMI
      > or = 25 are likely to require an alternative adult BP cuff if their blood
      pressure is to be measured precisely.

PMID- 8554950
TI  - Quality of life and care in Parkinson's disease.
AB  - Seventy-two parkinsonian patients attending a subregional movement disorder
      clinic completed a novel questionnaire designed to examine their quality of life
      and care. Significant problems with housing, travel, holidays and hobbies were
      identified. Financial difficulties due to premature retirement and the complex
      benefit system were found. Many carers were ill but, even when hospitalised,
      patients were cared for in the community by friends and relatives. Few patients
      had been referred for paramedical therapies, in spite of considerable disability
      in some cases. Aids and adaptations were commonly in use without advice from an
      occupational therapist. The specialised clinic and Parkinson's disease nurse
      advisor were welcomed by many patients. Most were satisfied with their hospital
      care and general practitioner, but follow-up arrangements with general
      practitioners were variable. It is suggested that further research concentrates
      on the roles of physiotherapy, speech therapy, nurse advisors and social workers
      in the management of Parkinson's disease, and on the value of increased carer
      support, including respite care.

PMID- 8554951
TI  - Onset of action of eformoterol by dry powder inhaler: objective and subjective
      measures.
AB  - This double-blind, randomised, placebo-controlled crossover trial in 18 adults
      with asthma evaluated the onset of efficacy of doses of 12 and 24 micrograms
      eformoterol delivered as a dry powder, and compared patients' subjective
      assessments of efficacy with objective measures. Bronchodilatory efficacy was
      measured in terms of specific conductance (sGaw) and forced expiratory volume in
      one minute (FEV1). With both doses of eformoterol, a bronchodilatory effect was
      observed one minute after inhalation. The difference in bronchodilator effect
      (sGaw and FEV1) between both eformoterol doses and placebo was statistically
      significant (p < 0.01) from one minute onwards. No significant difference in
      onset of action or peak effect was seen between the two doses of eformoterol.
      Patients' subjective reports were closely related to the observed onset of
      efficacy and indicated no difference between the two eformoterol doses.

PMID- 8554952
TI  - Use of antibiotics after complex open hand injury.
AB  - A prospective study undertaken to examine bacterial contamination at
      presentation, frequency and type of antibiotic prescribed, and outcome, in 50
      patients presenting with hand injuries of varying severity, is reported. Results
      of a national survey of trends in antibiotic prescribing for similar wounds in
      plastic surgery units are also recorded. Preoperative swabs cultured normal flora
      or no growth. Forty-eight patients received antibiotics with little consistency
      in the agent used, route of administration, or length of treatment. Clinical
      wound infection occurred in three crush injuries. No significant difference in
      the numbers of surgeons using antibiotics for clean and crushed injuries of all
      types was demonstrated. The state of the wound, rather than the tissue damaged,
      seemed to dictate antibiotic use. In dirty wounds, however, damage to deep
      structures appeared to be an indication for antibiotics--significantly fewer
      respondents treated dirty injuries of the skin alone. The authors believe that
      antibiotic use in open hand injury is of no proven benefit, and that this aspect
      of hand surgery requires further investigation.

PMID- 8554953
TI  - Hypovitaminosis D in the healthy elderly.
AB  - Hypovitaminosis D is a common finding in the healthy elderly population and has
      significant sequelae. No clear dietary or sunlight-related risk factors were
      identified by dietary assessment and modified outdoor score. Fortified liquid
      milk and vitamin supplements were associated with significantly higher serum 25
      hydroxyvitamin D levels. These results emphasise the need for foodstuff
      fortification and supplement use in the healthy elderly, as well as the 'high
      risk' housebound and institutionalised elderly.

PMID- 8554954
TI  - Audit of imported and domestic malaria cases at Kuala Lumpur Hospital.
AB  - The clinical, haematological and biochemical profiles of all domestic and
      imported malaria cases admitted to the Hospital Kuala Lumpur were analysed. The
      most common malaria types were Plasmodium falciparum (39.5%) and Plasmodium vivax
      (42%). The most common patient type was men aged 29-40 years (reflecting the high
      mobility of this group, many of whom were illegal immigrants). Misdiagnosis on
      admission was frequently due to the variable clinical presentation of the disease
      and the difficulties of obtaining an accurate history. Associated haematological
      abnormalities were common. Chloroquine resistance was diagnosed in four P.
      falciparum patients and in one P. falciparum/vivax patient. Overall, imported
      malaria did not seem more severe than domestic. The three patients with cerebral
      malaria survived. One patient died of acute liver failure. The large influx of
      illegal immigrants to Malaysia has resulted in a surge in malaria infection;
      illegal immigrants remain a source of chloroquine resistance.

PMID- 8554956
TI  - Pharmacological therapy for acute stroke: the future.
AB  - Stroke is a major cause of mortality, morbidity, and resource consumption. To
      reduce this burden, enormous efforts have focused on the development of drugs to
      limit brain damage. However, a breakthrough has not yet materialised, and data
      suggest that even if future drug trials do demonstrate a benefit, the overall
      impact of such drugs will be relatively limited. The pathophysiology of stroke is
      too complex to be markedly influenced by interruption of one or two components of
      the ischaemic cascade; intervention needs to be very soon post-stroke; and
      multiple pre-existing diseases and disabilities in elderly patients diminish
      their scope for recovery. In contrast, wider application of primary prevention,
      secondary prevention, and better organisation of services (eg setting up stroke
      units), could have a far greater effect on public health. Despite considerable
      enthusiasm for drug therapy in acute stroke, it is likely that the overall
      potential of such therapy will be disappointing.

PMID- 8554955
TI  - Post-traumatic stress disorder--a scar for life.
AB  - The symptoms of flashbacks, nightmares and hypervigilance may be understood by
      those who have shared or understand a traumatic event, but the duration of such
      symptoms may well outstretch all expectations. Post-traumatic stress disorder
      (PTSD) is serious, and may affect the rest of a sufferer's life. Traumatic
      situations are ubiquitous in the modern-day world, and can occur in both military
      and civilian settings. A great deal of research into the development and
      management of PTSD has been carried out in the past two decades; although many
      drug treatments and psychotherapeutic approaches have been investigated, no
      single method has been found to cure all the symptoms successfully.

PMID- 8554957
TI  - Undescended testes: screening and early operation.
AB  - The prevalence of undescended testes at birth, or cryptorchidism, is about 2-3%-
      higher among premature babies. Associated complications include infertility and
      malignancy, and a number of studies have shown that UK screening programs to date
      -the examinations carried out by the community services, for example--have failed
      to identify cryptorchidism at an early age in many cases. If complications,
      particularly infertility, are to be avoided, operations on undescended testes
      should be done before the age of two; at this age, operation may also be less
      disturbing for the patient. The cause of maldescent of the testes is uncertain,
      but there are related conditions, including exposure to oestrogens in the first
      trimester, and low birth weight: these need to be considered as they influence
      management.

PMID- 8554958
TI  - Deaths associated with warfarin in elderly patients.
AB  - The four cases presented illustrate fatal errors in the management of elderly
      patients at different stages in the chain of their anticoagulation treatment. As
      indications for anticoagulation increase in the elderly, more care needs to be
      taken.

PMID- 8554959
TI  - Epidermoid cyst (monodermal teratoma) of the testis.

PMID- 8554960
TI  - False-negative laparoscopy: a pitfall in the diagnosis of early ectopic
      pregnancy.

PMID- 8554961
TI  - Hypercalcaemia in an immobilised patient with pneumonia.
AB  - Hypercalcaemia is a serious complication of sepsis and prolonged immobility.
      Hormonal, humoral and mechanical factors play a complex role in its development.
      Because hypercalcaemia is associated with a significant increase in morbidity and
      mortality, early treatment is recommended. Pamidronate is an effective
      pharmacological agent and should be considered as primary therapy for this
      syndrome.

PMID- 8554962
TI  - Pyoderma gangrenosum: an unusual cause of periaural ulceration.
AB  - A case of pyoderma gangrenosum affecting the pinna and neck of a diabetic patient
      is reported. Appearances were suggestive of malignant otitis externa. A small
      biopsy resulted in rapid and aggressive exacerbation of the lesion. Pyoderma
      gangrenosum, although uncommon, should be considered as a cause of ulceration,
      particularly when the ulcer yields no growth on culture in a non-dependent area.

PMID- 8554963
TI  - Normalisation of slow-relaxing tendon reflexes (Woltman's sign) after cardiac
      pacing for complete heart block.
AB  - A patient whose slow-relaxing tendon reflexes returned to normal after cardiac
      pacing for complete heart block is reported. Since the patient was euthyroid,
      these observations add further weight to previous suggestions that intrinsic
      catecholaminergic mechanisms, as well as thyroid status, may play a role in the
      pathogenesis of slow-relaxing reflexes.

PMID- 8554964
TI  - Medical pregnancy termination in the presence of a massive uterine fibroid.
AB  - Surgical termination of pregnancy in the presence of uterine fibroids may be
      technically difficult resulting in reduced efficacy of the termination procedure.
      We describe the first documented use of RU486 and gemeprost in the successful
      medical termination of a pregnancy in a uterus grossly enlarged by fibroids.

PMID- 8554965
TI  - Low-dose maintenance clozapine treatment in the prophylaxis of bipolar affective
      disorder.
AB  - A chronically relapsing middle-aged man with bipolar affective disorder responded
      poorly to different forms of conventional pharmacotherapy, including depot
      antipsychotic medication and lithium. The addition of clozapine to lithium, even
      at doses as low as 25mg/day, led to a stabilisation of his mood. The withdrawal
      of low-dose clozapine led to a relapse within a few days. It is concluded that
      maintenance low-dose clozapine should be considered in bipolar disorders
      resistant to other treatments.

PMID- 8554966
TI  - Emphysematous cystitis in an elderly patient.

PMID- 8554967
TI  - Group A streptococcal toxic shock syndrome.

PMID- 8554968
TI  - Do telomerase antagonists represent a novel anti-cancer strategy?

PMID- 8554969
TI  - Phase II study of gemcitabine in patients with advanced pancreatic cancer.
AB  - The efficacy and safety of gemcitabine at a starting dose of 800 mg m2
      administered once a week for 3 weeks with 1 week's rest was investigated in
      chemonaive patients with advanced and/or metastatic pancreatic cancer. Of 34
      patients, 32 were evaluable for efficacy, 20 patients had metastatic stage IV
      disease, 25 had a performance status of 1 and 26 (76%) patients has significant
      pain on presentation. All responses were independently validated by an external
      oncology review board: two patients achieved a partial response that lasted 5.8
      and 5.2 months (6.3%) and six patients were stable for at least 4 weeks. The
      median duration of survival for evaluable patients was 6.3 months (range 1.6-19.2
      months). The tumour markers, CEA, CA 19-9 and CA 195 were serially measured in 16
      patients. There was a good correlation with tumour response when all three
      markers were significantly decreased. In 4 of 16 patients, tumour marker levels
      decreased by > or = 60%, including the two responders, one patient who survived
      for 12 months and one patient who showed objective tumour shrinkage but was
      deemed ineligible for response evaluation because the disease was considered not
      to be bidimensionally measurable. Symptomatic benefits included improvement in
      performance status (17.2%), analgesic requirement (7.4%), pain score (28.6%) and
      nausea (27.3%). The mean number of cycles administered was 2.5 and the mean
      dosage received was 890 mg m2 per injection. Seventy-four per cent of dose
      administrations were given on schedule. Toxicity, particularly haematological
      toxicity, reported as the maximum WHO grade experienced by patients was mild.
      Infective episodes were rare and limited to WHO grade 2 (6.7%). Nausea and
      vomiting was generally modest (WHO grade 3, 26.7%). Other side-effects included
      mild transient flu-like symptoms (seven patients) and peripheral oedema (three
      patients), which was not associated with abnormal cardiac hepatic or renal
      function. Gemcitabine has modest activity in pancreatic cancer, a limited
      positive improvement on a range of patient benefit parameters and has a mild
      toxicity profile. For these reasons and because of its novel mode of action,
      gemcitabine warrants further investigation in combination studies in pancreatic
      cancer.

PMID- 8554970
TI  - Type I and type III collagen metabolites in adult osteosarcoma patients.
AB  - Three biochemical markers of collagen metabolism were measured in 39 osteosarcoma
      patients. The pretreatment values did not predict outcome, and the markers showed
      no consistent change upon development of metastases. Both the age of the patients
      and the multimodality therapy affected the collagen metabolites. These findings
      emphasise the need for cautious interpretation of tumour-associated markers.

PMID- 8554971
TI  - Analysis of cytotoxic activity of the CD4+ T lymphocytes generated by local
      immunotherapy.
AB  - We previously reported that the anti-tumour effect of OK-432 is considerably
      enhanced by its intratumoral injection together with fibrinogen. In the present
      study, we generated killer T cells by culturing tumour-infiltrating lymphocytes
      from thyroid cancer patients who had received this local immunotherapy.
      Phenotypic analysis revealed that the T cells were positive for CD3+, CD4+, Leu8
      , CD45RO+ and T-cell receptor (TCR)alpha beta+, as well as showing strong surface
      expression of HLA-DR, CD25, LFA-1 and ICAM-1. The generated CD4+ T cells secreted
      interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, TNF-beta, and
      interleukin (IL)-6 (but not IL-4), and exhibited a high level of cytolytic
      activity against several tumour cell lines. The cytolytic activity of these T
      cells for Daudi cells was inhibited by preincubation with an anti-intercellular
      adhesion molecule (ICAM)-1 antibody, but not by preincubation with anti-TCR alpha
      beta, anti-CD2, or anti-LFA-1 antibodies. Pretreatment with anti-ICAM-1 antibody
      inhibited T-cell cytolytic activity, but not conjugation with target cells. In
      addition, incubation with immobilised anti-ICAM-1 enhanced the secretion of IFN
      gamma by T cells. We conclude that ICAM-1 expressed on the effector cytotoxic
      CD4+ T lymphocytes delivers regulatory signals that enhance IFN-gamma secretion.

PMID- 8554972
TI  - Towards quality control in cancer chemotherapy.
AB  - A survey of all hospital pharmacies in the former North Western Regional Health
      Authority has revealed that hospital personnel continue to prepare cytotoxic
      drugs in suboptimal conditions, despite the widespread introduction of pharmacy
      cytotoxic reconstitution services. Other concerns include the lack of formal
      training for medical staff in the administration of these agents and the frequent
      absence of written procedures for dealing with extravasation and chemotherapy
      errors.

PMID- 8554973
TI  - Hepatocyte growth factor levels in bone marrow plasma of patients with leukaemia
      and its gene expression in leukaemic blast cells.
AB  - Hepatocyte growth factor (HGF) has been known as a multiple function factor,
      which also stimulates early haematopoiesis. In this study, we found that HGF was
      expressed at both the RNA and protein levels in acute myeloid leukaemia (AML) and
      chronic myeloid leukaemia (CML). In patients with AML (n = 20) and CML (n = 5),
      bone marrow plasma HGF concentrations were 20.44 +/- 6.26 (mean +/- s.e.) ng ml-1
      and 7.17 +/- 0.53 ng ml-1 respectively. These were significantly higher (P <
      0.01) than the value for normal subjects (n = 26): mean 0.92 +/- 0.09 ng ml-1.
      Constitutive HGF production was observed in freshly prepared leukaemic blast
      cells from three patients with high HGF levels of bone marrow plasma. Expression
      of HGF mRNA was correlated with bone marrow plasma HGF levels. After complete
      remission was obtained in six patients, bone marrow plasma HGF levels were
      significantly decreased. In contrast, the HGF mRNA was less abundantly expressed
      in acute lymphoid leukaemia (ALL). In patients with ALL (n = 5), bone marrow
      plasma HGF concentration (0.69 +/- 0.14 ng ml-1) remained low within the value
      for normal subjects. These results suggest that some populations of myeloid
      lineage cells have the ability to produce HGF.

PMID- 8554974
TI  - Human papillomavirus DNA as a factor determining the survival of bladder cancer
      patients.
AB  - The natural history of transitional cell carcinoma (TCC) of the urinary bladder
      is somewhat variable, with a significant number of tumour recurrences that
      occasionally evolve towards an infiltrating disease. The aim of this study was to
      investigate the presence of human papillomavirus (HPV) DNA in 76 TCC specimens,
      and then correlate such findings with the overall patient survival. However,
      other classical prognostic clinical and pathological variables such as
      pathological grade and stage, koilocytosis, age and sex were also tested. HPV DNA
      was investigated by means of the highly sensitive polymerase chain reaction
      (PCR). DNA primers specific for HPV types 6, 11, 16 and 18 were used. Our results
      showed that 7 (9.21%) out of 76 such cases were reactive for HPV 16 DNA; one of
      them also reacted with HPV 6 DNA. The statistical analysis was done by the Kaplan
      Meier method, Wilcoxon's generalised test for studying the differences in
      survival curves and Cox's regression analysis for independent prognostic factors.
      A significant P-value was found for pathological grade (P < 0.0001) and stage (P
      < 0.0001), HPV 16 DNA (P = 0.0418) and koliocytosis (P = 0.0140). Thus,
      pathological grade was the only independent factor in the bladder cancer
      survival. These observations may prove useful in prognostic stratification of
      patients with TCC of the bladder.

PMID- 8554975
TI  - Incidence of primary liver cancer and aetiological aspects: a study of a defined
      population from a low-endemicity area.
AB  - The prevalence of primary liver cancer (PLC) varies throughout the world. It has
      been attributed to variations in incidence of the predominant histological type,
      hepatocellular carcinoma (HCC). The incidence of PLC types other than HCC such as
      cholangiocellular carcinoma (CCC) is far less known, especially in low-incidence
      areas. The aetiology of HCC and other PLC types is obscure, with the exception of
      the association between HCC and cirrhosis as well as chronic viral hepatitis. The
      present retrospective incidence and aetiology study concerns a well-defined
      population from a period with a high autopsy frequency. Preserved biopsy
      specimens were re-evaluated histopathologically and patient records were studied.
      Among 590 histologically verified cases of PLC, HCC constituted 90%, CCC 8% and a
      mixed form of these types 1%. At the end of the study period the annual age
      standardised incidence rate of HCC was 3.6 cases per 100,000 inhabitants. Other
      PLC types were hepatoblastoma (n = 3), fibrolamellar carcinoma (n = 2),
      angiosarcoma (n = 1) and infantile haemangioendothelioma (n = 1), each
      constituting less than 1% of the PLC cases. Comparing HCC with CCC we found that
      cirrhosis (70%) and alcoholism (21%) was significantly more frequent in HCC, and
      cholelithiasis was significantly more common (60%) in patients with CCC. In the
      majority of the PLC cases with liver cirrhosis this disorder was unknown before
      diagnosis of the tumour.

PMID- 8554976
TI  - Apparent bypass of negative selection in CD8+ tumours in CD2-myc transgenic mice.
AB  - A role for antigen stimulation in lymphoid neoplasia has been postulated and is
      supported by indirect evidence that suggests that the interaction of antigen with
      both T cells and B cells may constitute an epigenetic event that can contribute
      to tumour induction or tumour progression. Using myc-bearing transgenic mice that
      develop mainly clonal T-cell lymphomas we have investigated the possibility that
      endogenous antigen-mediated clonal deletion might be overridden in tumorigenesis.
      CD2-myc transgenic mice were backcrossed on to a CBA/Ca background to ensure Mtv
      mediated deletion of V beta 11-expressing T cells in the resultant offspring.
      Lymphomas arising from these mice were subsequently screened for V beta 11
      expression. There was a clear correlation between the age at which mice developed
      neoplasia and the tumour phenotype. Mice with CD4- CD8+ tumours succumbed to
      thymic lymphoma at a significantly younger age than mice developing CD4+ CD8+
      tumours. A small number of tumours consisted of the 'forbidden' V beta 11
      phenotype, showing that cells vulnerable to transformation could escape negative
      selection. The majority of the V beta 11-positive tumours were CD4- CD8+ and were
      only observed in mice showing clinical evidence of tumour development at a
      relatively young age. The phenotype of these cells and the age at which tumours
      arose suggests that T cells escaping tolerance may be susceptible to
      transformation.

PMID- 8554977
TI  - Cisplatin and taxol activate different signal pathways regulating cellular injury
      induced expression of GADD153.
AB  - Signal transduction pathways activated by injury play a central role in
      coordinating the cellular responses that determine whether a cell survives or
      dies. GADD153 expression increases markedly in response to some types of cellular
      injury and the product of this gene causes cell cycle arrest. Using induction of
      GADD153 as a model, we have investigated the activation of the cellular injury
      response after treatment with taxol and cisplatin (cDDP). Activation of the
      GADD153 promoter coupled to the luciferase gene and transfected into human
      ovarian carcinoma 2008 cells correlated well with the increase in endogenous
      GADD153 mRNA after treatment with taxol but not after treatment with cDDP.
      Following treatment with cDDP, the increase in endogenous GADD153 mRNA was 10
      fold greater than the increase in GADD153 promoter activity. Likewise, at
      equitoxic levels of exposure (IC80), cDDP produced a 5-fold greater increase in
      endogenous GADD153 mRNA than taxol. The tyrosine kinase inhibitor tyrophostin B46
      had no significant effect on the ability of taxol to activate the GADD153
      promoter, but inhibited activation of the GADD153 promoter by cDDP in a
      concentration-dependent manner. Tyrphostin B46 synergistically enhanced the
      cytotoxicity of cisplatin; however, the same exposure had no significant effect
      on the cytotoxicity of taxol. We conclude that (1) taxol and cDDP activate
      GADD153 promoter activity through different mechanisms; (2) the signal
      transduction pathway mediating induction by cDDP involves a tyrosine kinase
      inhibitable by tyrphostin B46; and (3) that inhibition of this signal
      transduction pathway by tyrphostin synergistically enhances cDDP toxicity.

PMID- 8554978
TI  - Effect of tumour cell-conditioned medium on endothelial macromolecular
      permeability and its correlation with collagen.
AB  - Conditioned medium prepared from mouse melanoma B16 cells (B16-CM) increases the
      macromolecular permeability of bovine aortic, venous and human umbilical vein
      endothelial monolayer. Collagen, which is synthesised by endothelial cells, has
      an important function in regulating the permeability of endothelial monolayer.
      Briefly, low collagen content leads to hyperpermeable structure of the
      endothelial monolayer. In the present studies, we examined the relationship
      between the increase of endothelial permeability and content of synthesised
      collagen of endothelial cells cultured with B16-CM. The B16-CM reduced
      endothelial collagen content but did not digest collagen directly. Matrix
      metalloproteinase inhibitor, 1,10-phenanthroline, inhibited the increase in
      permeability due to addition of B16-CM. These data suggest that B16-CM acts on
      endothelial cells, stimulating the digestion of endothelial collagen, and that
      the reduced content of collagen leads to the hyperpermeability of the endothelial
      monolayer.

PMID- 8554979
TI  - p53 protein as a prognostic indicator in breast carcinoma: a comparison of four
      antibodies for immunohistochemistry.
AB  - We examined the reactivity of four p53-specific monoclonal antibodies--PAb 1801,
      p53-BP-12, D07 and CM1--on sections of formalin-fixed tissue collected from 245
      breast carcinomas. Immunodetection of p53 varied between 37.6% and 46.6%. The
      greatest variation was observed among lobular carcinomas and low-grade tumors in
      which immunodetection varied between 8.3% and 27.3%. In contrast, immunodetection
      of p53 in invasive ductal carcinomas was subject to a lower degree of variability
      with between 40.6% and 49.7% of these tumours proving to be positive. In general,
      we found antibodies PAb 1801 and DO7 to be the most effective in immunolocalising
      p53. Immunodetection of p53 with each of the four antibodies was found to
      correlate strongly with tumour grade. In survival analysis, the results gained
      using antibody PAb 1801 proved to be of greatest statistical significance and to
      provide the strongest index of prognosis. A significant relationship was observed
      between immunodetection of p53 with each of the four antibodies and poor
      responsiveness to endocrine therapy. In addition, relationships were also
      observed between p53 immunostaining and tumour oestrogen receptor (ER) status as
      well as c-jun expression. We observed no correlation between abnormalities of the
      p53 and the Rb gene products or between elevated c-erbB-2 or epidermal growth
      factor receptor (EGFR) expression and immunodetection of p53.

PMID- 8554980
TI  - Dietary fish oil (MaxEPA) enhances pancreatic carcinogenesis in azaserine-treated
      rats.
AB  - In the present study the putative chemopreventive effect of dietary fish oil
      (MaxEPA) on azaserine-induced pancreatic carcinogenesis in rats was investigated.
      Groups of rats were maintained on a semipurified low-fat (LF; 5 wt%) diet or on
      semipurified high-fat (HF; 25 wt%) diets containing 5 wt% linoleic acid (LA) and
      including 0.0, 1.2, 2.4, 4.7, 7.1 or 9.4 wt% MaxEPA. Animals fed a HF diet
      developed significantly higher mean numbers of atypical acinar cell nodules
      (AACNs), adenomas and carcinomas than animals fed a LF diet. Dietary MaxEPA
      caused a significant (P < 0.01) dose-related increase in mean number of AACNs
      (0.5 < phi < 3.0 mm). The mean number of adenomas and carcinomas remained similar
      among the groups. Cell proliferation was significantly lower in AACNs from
      animals fed HF containing 9.4% MaxEPA in comparison with HF without MaxEPA and
      with LF. LA levels had increased and arachidonic acid (AA) levels had decreased
      in blood plasma and pancreas with increasing dietary MaxEPA. Feeding MaxEPA
      resulted in significant decreases in 6-keto-prostaglandin (PG) F1 alpha (P <
      0.05) and PGF2 alpha (P < 0.01) in non-tumorous pancreas, whereas PGE2, PGF2
      alpha and thromboxane B2 (TXB2) levels were significantly (P < 0.001) higher in
      pancreatic tumour tissue than in non-tumorous pancreatic tissue. It is concluded
      that (i) dietary MaxEPA enhances dose-relatively growth of putative preneoplastic
      AACNs in the pancreas of azaserine-treated rats; (ii) dietary MaxEPA inhibits the
      conversion of LA to AA, as well as the conversion of AA to TXB2 or PGF2 alpha in
      non-tumorous pancreatic tissue; (iii) the high levels of PGE2, PGF2 alpha and
      TXB2 in pancreatic adenocarcinomas indicate a possible role for these eicosanoids
      in modulation of tumour growth.

PMID- 8554981
TI  - Susceptibility to multiple cutaneous basal cell carcinomas: significant
      interactions between glutathione S-transferase GSTM1 genotypes, skin type and
      male gender.
AB  - The factors that determine development of single and multiple primary cutaneous
      basal cell carcinomas (BCCs) are unclear. We describe a case-control study
      firstly, to examine the influence of allelism at the glutathione S-transferase
      GSTM1 and GSTT1 and cytochrome P450 CYP2D6 loci on susceptibility to these
      tumours and, secondly, to identify interactions between genotypes and relevant
      individual characteristics, such as skin type and gender. Frequency distributions
      for GSTM1 genotypes in cases and controls were not different, although the
      frequency of GSTM1 A/B was significantly lower (P = 0.048) in the multiple BCCs
      than in controls. We found no significant differences in the frequencies of GSTT1
      and CYP2D6 genotypes in cases and controls. Interactions between genotypes were
      studied by comparing multinomial frequency distributions in mutually exclusive
      groups. These identified no differences between cases and controls for
      combinations of the putatively high risk GSTM1 null, GSTT1 null, CYP2D6 EM
      genotypes. Interactions between GSTM1 A/B and the CYP2D6 PM and GSTT1-positive
      genotypes were also not different. Frequency distributions of GSTM1 A/B with
      CYP2D6 EM in controls and multiple BCCs were significantly different (P = 0.033).
      The proportion of males in the multiple BCC group (61.3%) was greater than in
      controls (47.0%) and single BCC (52.2%), and the frequency of the combination
      GSTM1 null/male gender was significantly greater in patients with multiple
      tumours (P = 0.002). Frequency distributions of GSTM1 null/skin type 1 were also
      significantly different (P = 0.029) and the proportion of subjects who were GSTM1
      null with skin type 1 was greater (P = 0.009) in the multiple BCC group. We
      examined the data for interactions between GSTM1 null/skin type 1/male gender by
      comparing frequency distributions of these factors in the single and multiple BCC
      groups. The distributions were almost significantly different (exact P = 0.051).
      No significant interactions between GSTT1 null or CYP2D6 EM and skin type 1 were
      identified. Comparisons of frequency distributions of smoking with the GSTM1
      null, GSTT1 null and CYP2D6 EM genotypes identified no differences between
      patients with single and multiple tumours.

PMID- 8554982
TI  - Hexadecafluorinated zinc phthalocyanine: photodynamic properties against the EMT
      6 tumour in mice and pharmacokinetics using 65Zn as a radiotracer.
AB  - Hexadecafluorinated zinc phthalocyanine (ZnPcF16), an analogue of zinc
      phthalocyanine (ZnPc) in which all hydrogen atoms have been substituted by
      fluorine, was prepared as a single isomeric product via the condensation of
      tetrafluorophthalonitrile with zinc acetate. Fluorination renders the ZnPc
      soluble in most common solvents. The photodynamic properties and pharmacokinetics
      of the ZnPcF16 were evaluated in EMT-6 tumour-bearing Balb/c mice using 65Zn
      radiolabelled analogues. Both dyes, administered i.v. at 1 mumol kg-1 as
      Cremophor emulsions, revealed good tumour uptake [approximately 8-9 per cent of
      the injected dose per g tissue (%IDg-1)] at 24 h post injection (p.i.), with the
      fluorinated dye reaching higher concentrations (approximately 11%IDg-1) at 48 h
      p.i. and subsequently higher tumour-blood ratios due to rapid blood clearance.
      ZnPcF16 at a dose of 5 mumol kg-1 (4.3 mg kg-1) induced complete tumour
      regression after phototherapy (24 h p.i., 650-700 nm band, 360 J cm-2, 200 mW cm
      1). At a dose of 2 mumol kg-1 and phototherapy at 24 h p.i., the tumour volume
      doubling time increased to 11 days vs 6 days for the control tumours. A similar
      tumour growth delay was observed when phototherapy was conducted at 48 h or 72 h
      after dye injection implying that tumour response correlates with tumour dye
      concentrations rather than serum concentrations. As a result of its low
      solubility, the administered dose of ZnPc was limited to 1 mumol kg-1 and at this
      drug level significant tumour response was only observed when the dye was
      solubilised as the pyridinium salt. Isolation of the neoplastic cells after in
      vivo dye administration and in vitro exposure to red light followed by a colony
      formation assay showed that the ZnPcF16 exhibited a 1-2 order of magnitude higher
      potential for direct cell killing as compared with Photofrin and about a five
      times lower efficiency than ZnPc. However, all three photosensitisers induced
      complete occlusion of tumour vasculature immediately after PDT, suggesting that
      tumour regression mainly resulted from vascular stasis. The ZnPcF16 offers
      several advantages over ZnPc for clinical applications, including improved
      solubility in most solvents, resulting in facilitated drug formation, favourable
      pharmacokinetics as well as the potential use in fluorine magnetic resonance (F
      MR) imaging.

PMID- 8554983
TI  - Oestrogen receptor: a stable phenotype in breast cancer.
AB  - Oestrogen receptor (ER) expression in breast cancer is regarded as a phenotype
      that may change during the natural history of the disease or during endocrine
      therapy. It has been suggested that in up to 70% of tumours that show acquired
      resistance the mechanism may be changed in ER status from positive to negative.
      This paper proposes an alternative hypothesis that ER expression in a stable
      phenotype in breast cancer. The paper reviews the literature on ER expression
      during the natural history of breast cancer in patients and also presents data on
      the effect of endocrine therapy on ER expression. If the alternative hypothesis
      is true it has important implications for treatment from chemoprevention to
      acquired endocrine resistance in advanced disease. Equally, if the hypothesis is
      true, attempts to develop laboratory models of endocrine resistance where ER
      positive tumours become ER negative need to be re-evaluated.

PMID- 8554985
TI  - Early detection of treatment response by diffusion-weighted 1H-NMR spectroscopy
      in a murine tumour in vivo.
AB  - Nuclear magnetic resonance (NMR) non-invasively measures the apparent diffusion
      coefficient (ADC) of water, which is sensitive to the biophysical characteristics
      of tissue. Because anti-cancer treatment alters tumour pathophysiology, tumour
      ADC may be altered by treatment. In order to test this hypothesis, ADC was
      measured in s.c. implanted murine RIF-1 tumours before and up to 9 days after
      treatment with cyclophosphamide. A dose-dependent, reversible increase in tumour
      ADC was observed after cyclophosphamide treatment, which is consistent with an
      increase in the fraction of interstitial water due to treatment-induced cell
      death. Because tumour water ADC is increased substantially at a time when there
      is no change in tumour volume for a dose which produces minimal cell kill, its
      measurement could provide a novel means for early detection of response to anti
      cancer therapy. If the changes in ADC observed in the present study are evident
      for commonly used anti-cancer therapies in different tumour types and specific to
      a therapeutic response, the approach could be broadly applicable as a response
      predictor since magnetic resonance imaging can be used to measure ADC in human
      tumours.

PMID- 8554984
TI  - Characteristics of cancer cell death after exposure to cytotoxic drugs in vitro.
AB  - The characteristics of cell death were investigated after exposure of CCRF-CEM.f2
      cells to five drugs over a broad concentration range; these were the
      glucocorticoid dexamethasone (DXM), the mitotic inhibitor vincristine (VIN) and
      three antimetabolites, methotrexate (MTX), 5'-fluoro-2'-deoxyuridine (FUdR) and
      5'-fluorouracil (5-FU). Drug-treated cells were monitored for cell death
      mechanisms at different times by examining the pattern of DNA degradation, cell
      morphology and flow cytometric profile, together with effects on cell growth over
      72 h. At growth-inhibitory drug concentrations, the first changes were cell cycle
      perturbations detectable after 4-6 h of drug exposure. The appearance of features
      characteristic of apoptotic cell death was noted after all drug treatments in the
      CCRF-CEM.f2 cell line, but the pattern and kinetics varied considerably. VIN
      induced apoptotic changes by 12 h, while DXM treatment caused apoptosis only
      after 48 h. Both MTX and FUdR induced morphological changes characteristic of
      apoptosis at least 24 h before internucleosomal DNA cleavage, which was
      detectable only after 48 h. In contrast, 5-FU did not cause internucleosomal DNA
      cleavage by 48 h at any concentration, despite the presence of morphologically
      apoptotic cells 24 h earlier. These data suggest that disruption of the cell
      cycle caused by drug treatment may be the common trigger initiating the drug
      specific apoptotic sequence of dying cells.

PMID- 8554986
TI  - An inbred colony of oncogene transgenic mice: diversity of tumours and potential
      as a therapeutic model.
AB  - Transgenic mice carrying the activated rat c-neu oncogene under transcriptional
      control of the MMTV promoter were backcrossed to BALB/c mice, with the aim of
      developing a model for cancer therapy. A total of 86 of 268 transgene-positive
      mice in the first five generations developed 93 histologically diverse tumours
      (median age of onset 18 months). The cumulative incidence of breast tumours at 24
      months was 18%, and overall tumour incidence 31%. As well as expected c-neu
      expressing breast cancers, lymphomas and Harderian gland carcinomas developed.
      Virgin mice had fewer mammary tumours than those with two litters. Breast
      carcinomas metastasised to the lungs, and lymphomas were widely disseminated. The
      tumours showed a range of architectural patterns, which resembled human breast
      cancers or lymphomas. This diversity was reflected in S-phase fraction and
      aneuploidy. Breast tumours transplanted to nude mice showed variable responses to
      interferon (IFN)-alpha and gamma. A tumour transplanted to BALB/c mice responded
      to interleukin (IL)-12. There was significant decline in transgene positivity
      with successive generations. The diversity, histological and biological
      resemblance to human cancer suggests that the model has potential for evaluating
      novel therapies. However, further genetic and environmental manipulations are
      required to increase tumour incidence and decrease age of onset.

PMID- 8554987
TI  - Proliferative response of human prostate tumour xenografts to surgical trauma and
      the transurethral resection of the prostate controversy.
AB  - Transurethral resection of the prostate (TURP) as an excisional procedure
      involving multiple incisions into the prostate does not differentiate between
      palpably benign prostate tissue and microscopic foci of well-differentiated
      adenocarcinoma. The impact of TURP on the progression of such 'latent' or
      'incidental' tumours unique to the prostate gland has been a focal point of a
      continuing controversy. In studies designed to develop preclinical evidence that
      would lend support to, or detract from, either side of the TURP controversy,
      surgical trauma-induced stimulation of in situ tumour growth was extended to
      include human prostate tumour tissue PC-3, DU-145 and H-1579, albeit as
      xenografts in athymic nude males. A significant proliferative response of
      prostate tumours implanted directly in, adjacent to, or distant from, a freshly
      induced surgical wound, could be inhibited by a somatostatin analogue
      (Lanreotide) applied topically to the surgical site. This preclinical model
      supports TURP as a risk factor for biopsy or therapeutic surgical intervention
      procedures in benign prostatic hypertrophy (BPH), a risk factor that increases
      with the stage of disease in undetected cancers. It also suggests a potential
      clinical benefit that might be derived by applying Lanreotide directly to the
      surgically traumatised genitourinary area by simple irrigation of the urethra and
      bladder during or shortly post TURP.

PMID- 8554988
TI  - Induction of tumour cell shedding into effluent venous blood breast cancer
      surgery.
AB  - Surgeons have long been concerned that cancer may be disseminated by shedding of
      tumour cells into the bloodstream during surgery. Early claims that cancer
      operations induced an increase in the number of tumour cells shed into the
      circulation were subsequently discredited, and the issue has remained unresolved.
      We used immunocytochemistry for cytokeratins to detect tumour cells in effluent
      blood from breast carcinomas in 18 patients undergoing surgery. Tumour cells were
      detectable in 6/18 patients during surgery, in only one patient before operation
      and in none post-operatively (P = 0.025). Circulating cells were associated with
      vascular invasion within the primary tumour (P = 0.032). No cytokeratin-positive
      cells were found in blood from ten normal volunteers or four patients undergoing
      surgery for other breast conditions. These results confirm that cancer surgery in
      humans results in an increase in the shedding of tumour cells into the
      circulation. The implications for prognosis and practice should be determined by
      larger prospective studies.

PMID- 8554989
TI  - Cytokeratin-positive cells in bone marrow for identifying distant micrometastasis
      of gastric cancer.
AB  - Direct evidence of tumour seeding in distant organs at the time of surgery for
      gastric cancer is not available. An immunocytochemical assay for epithelial
      cytokeratin protein may fill this gap since it is a feature of epithelial cells
      that would not normally be present in bone marrow. The bone marrow of 46 patients
      with primary gastric cancer was examined for tumour cells, using
      immunocytochemical techniques and antibody reacting with cytokeratin, a component
      of the intracytoplasmic network of intermediate filaments. The monoclonal
      antibody CK2 recognises a single cytokeratin polypeptide (human cytokeratin no.
      18) commonly present in epithelial cells. The expression of tumour-suppressor
      genes p53 and RB for the primary lesion was also determined using the monoclonal
      antibodies PAb 1801 and 3H9 respectively, and the proliferating activity was
      determined by the Ki-67 antigen labelling index for MIB-1 antibody staining. Of
      these 46 patients, 15 (32.6%) presented with cytokeratin-positive cells at the
      time of primary surgery. The positive findings were related to the
      undifferentiated tissue type and to the prominent depth of invasion, but not to
      other clinicopathological factors. In 2 of 15 (13.3%) patients, the depth of
      invasion was limited to the mucosa. The metastatic potential to bone marrow did
      not relate to expressions of p53 and RB genes, or to the proliferating activity
      of MIB-1 staining for the primary lesion of gastric cancer. As tumour cells in
      bone marrow are indicative of the general disseminative capability of an
      individual tumour, this technique may be useful for identifying patients at high
      risk of metastasis from a gastric tumour.

PMID- 8554990
TI  - Occult axillary node metastases in breast cancer: their detection and prognostic
      significance.
AB  - Although the presence of axillary node metastases in breast cancer is a key
      prognostic indicator and may influence treatment decisions, a significant
      proportion of patients diagnosed as axillary node negative (ANN) using standard
      histopathological techniques may have occult nodal metastases (OMs). A
      combination of limited step-sectioning (4 x 100 microns intervals) and
      immunohistochemical staining (with cytokeratin (MNF.116) and MUC1 (BC2)
      antibodies) was used to detect OM in a retrospective series of 208 ANN patients.
      OMs were found in 53 patients (25%), and both step-sectioning and
      immunohistochemical detection significantly improved detection (P < 0.05).
      Detection using BC2 (25%) was superior to MNF.116 (18%) and haematoxylin and
      eosin (H&E) (8%). OMs were found in 51 patients using only the first and deepest
      sectioning levels and BC2 staining. OMs were more frequently found in lobular
      (38%) than ductal carcinoma (25%), and more frequently in women less than 50
      years (41%) than in older women (19%). Univariate overall and disease-free
      survival analyses showed that the presence, size and number of OM had prognostic
      significance as did tumour size (disease-free only) and histological and nuclear
      grade (P > 0.05). Cox multivariate proportional hazard regression analyses showed
      that the presence and increasing size of OMs were significantly associated with
      poorer disease-free survival, independently of other prognostic factors (P <
      0.05). However there was not a significant independent association of the
      presence of occult metastases with overall survival (P = 0.11). These findings
      have important implications with regard to selection of ANN patients for adjuvant
      therapy.

PMID- 8554991
TI  - Putrescine accumulation in human pulmonary tumours.
AB  - Type II pneumocytes and Clara cells, both epithelial cells that possess an active
      uptake system for polyamines, have been identified as possible precursor cells of
      at least some types of lung tumours. In this study we have investigated whether
      human pulmonary tumours exhibit putrescine uptake. Lung slices from both tumoral
      tissue and non-tumoral tissue, obtained from patients undergoing surgery for lung
      cancer, were incubated with radiolabelled putrescine at both 37 degrees C and 4
      degrees C. The accumulation of putrescine was evaluated by its apparent kinetic
      parameters, in the presence or absence of cystamine, and by autoradiography. The
      investigated tumoral tissue (six squamous carcinomas and five adenocarcinomas)
      did not show accumulation of putrescine above that attributable to simple
      diffusion, except for one adenocarcinoma. In this specimen autoradiography showed
      that the accumulation was not specifically associated with any particular cell
      type, but that practically every cell accumulated putrescine. We conclude that
      human pulmonary tumours do not accumulate polyamines in a manner similar to
      normal pulmonary epithelial cells.

PMID- 8554992
TI  - Outreach work in HIV prevention effective.

PMID- 8554993
TI  - Racism: fact or fiction?

PMID- 8554994
TI  - A pioneer in care.

PMID- 8554995
TI  - Evaluating groups in learning disabilities.
AB  - Groupwork can be effective in meeting a range of needs presented by students with
      profound learning disabilities. This article describes the process involved in
      setting up groups for these students, and includes examples of a group session
      and methods for evaluating groupwork.

PMID- 8554996
TI  - How to conduct a literature review.
AB  - Literature reviews require a range of skills if they are to be carried out
      successfully. This article details some of the skills required and how they can
      be integrated to produce a review relevant to practice.

PMID- 8554997
TI  - Atopic childhood eczema (continuing education credit).

PMID- 8554998
TI  - Elderly care: nursing home nightmare.

PMID- 8554999
TI  - Workface: downgrading.

PMID- 8555001
TI  - Let's hear more from nurses.

PMID- 8555000
TI  - Agency advantages.

PMID- 8555002
TI  - Cardiology update. A century of X-rays.

PMID- 8555003
TI  - Cardiology update. HeartMate--left ventricle assist device.

PMID- 8555004
TI  - Cardiology update. Cardiac alert.

PMID- 8555005
TI  - Cardiology update. 'Live' rhythm strip.

PMID- 8555006
TI  - Cardiology update. Percutaneous tracheostomy.

PMID- 8555007
TI  - 8-Methoxypsoralen photoadduct formation in complementary oligonucleotides
      containing a cross-linkable site.
AB  - The complete profile of 8-methoxypsoralen photoadduct formation in complementary
      oligonucleotides (5'-GAGTATGAG and 5'-CATAC) has been determined. Equimolar
      solutions of the oligonucleotides were irradiated at 4 degrees C in order to
      stabilize the mini-double helix. Photomodified oligonucleotides were separated by
      reversed phase chromatography on a Vydac C4 column. Photoadduct formation favored
      the 5'TAT site in the 9mer over the 5'ATA site in the 5mer by a factor of two.
      Split-dose studies showed that the monoadducts formed on GAGTATGAG were
      preferentially converted to cross-links by an additional UVA exposure.

PMID- 8555008
TI  - Efficacy of ultraviolet B phototherapy for psoriasis in patients infected with
      human immunodeficiency virus.
AB  - To evaluate the efficacy of ultraviolet B (UVB) phototherapy for the treatment of
      psoriasis in patients infected with human immunodeficiency virus (HIV), the
      response of 14 patients was compared to that of matched seronegative control
      individuals. All patients were evaluated prior to treatment (baseline) and after
      21 treatments for the extent of total body surface area (TBSA) involvement and
      the quantification of scale, erythema, and thickness of  plaques using a scale of
      0 (absent) to 4 (severe). The only concomitant medication allowed was salicylic
      acid in petrolatum. The cumulative score for scale, erythema, and thickness
      improved 1.9 +/- 0.5 [mean +/- standard error of mean (SEM)] in the HIV group and
      2.4 +/- 0.3 in controls. There was 40.9 +/- 7.3% reduction of TBSA involvement in
      the former and 38.4 +/- 7.6% reduction in the latter group. None of the
      differences was statistically significant. There was no statistically significant
      difference in the response to therapy among various stages of immunosuppression
      in the HIV group. There was also no deterioration of immune status in this group.
      UVB phototherapy is an effective treatment for psoriasis in patients infected
      with HIV. The response is identical to that of matched control individuals.

PMID- 8555009
TI  - In vitro mechanism(s) of ultraviolet-induced tumor necrosis factor-alpha release
      in a human keratinocyte cell line.
AB  - It has been demonstrated that ultraviolet (UV) irradiation is able to induce both
      in vivo and in vitro, tumor necrosis factor-alpha (TNF) release. The purpose of
      the present study was to evaluate, using a human keratinocyte cell line NCTC
      2544, the mechanism(s) of UV-induced TNF release and the ability of commonly used
      sunscreens to modulate UV-induced TNF release. TNF release can be partially
      prevented both by adding an anti-human IL-1 alpha antibody after irradiation,
      suggesting an autocrine effect of IL-1 alpha in inducing TNF release, and by
      adding antioxidants indicating also a role of oxidant species. TPCK, a I kappa-B
      alpha protease inhibitor, was able to virtually abolish UV-induced TNF release,
      indicating that UV-induced TNF release requires NF-kappa B activation. Anti-human
      IL-1 beta antibody was ineffective as expected, considering that keratinocytes
      are unable to process pre-IL-1 beta to its active form. To evaluate the
      sunscreen's modulation on UV-induced TNF release, confluent cells were
      irradiated, in the presence or absence of the tested sunscreens (Uvinul MS40,
      Uvinul P25 and Uvinul DS49). Different IC50 values could be calculated, which may
      be related to different UV absorption spectrums: Uvinul MS40 offers great
      protection by virtue of its broader absorption spectrum, closely followed by
      Uvinul P25 and finally by Uvinul DS49.

PMID- 8555010
TI  - Neoplastic transformation of neonatal human fibroblasts exposed in vitro to
      radiation from a quartz-halogen lamp.
AB  - The use of unfiltered quartz-halogen lamps exposes human skin to radiation that
      spans much of the ultraviolet (UV) spectrum. Reports indicate that exposure to
      quartz-halogen lamps is erythemogenic, mutagenic, and carcinogenic. To compare
      the carcinogenic potential of quartz-halogen lamps with that of other UV sources,
      we determined the dose dependence for cytotoxicity and neoplastic transformation
      in neonatal human fibroblasts exposed in vitro to: a 15 W germicidal lamp
      (primarily 254 nm radiation), a 15 W Cool White fluorescent lamp, and an
      unfiltered 20 W quartz-halogen lamp. Fluence-survival relationships were
      multiphasic with linear dose response below about 40% survival, and all three
      sources produced fluence-dependent transformation as indicated by induction of
      anchorage-independent growth. Maximum transformation frequencies were observed at
      fluences of 5-8 J/m2 for the germicidal lamp, 6.3 kJ/m2 for the fluorescent lamp,
      and 300 J/m2 for the quartz-halogen lamp. These data confirm the carcinogenic
      potential of the quartz-halogen lamp.

PMID- 8555012
TI  - Ultraviolet A-induced photodegradation of 5-methoxypsoralen, 8-methoxypsoralen
      and psoralen reduces the biological effectiveness of the furocoumarins in vivo.

PMID- 8555011
TI  - Long-wave ultraviolet radiation causes increase of membrane-bound fraction of
      protein kinase C in rat myeloid leukemia cells.
AB  - We examined the effect of long-wave ultraviolet radiation (UVA) on protein kinase
      C (PKC) and on the proliferation of rat myeloid leukemia cell line (ChL).
      Exposure of cells to a single dose of UVA (8 J/cm2 at 372 +/- 10 nm) caused a
      rapid increase in the quantity of the membrane-bound PKC, as assessed by 3H
      phorbol ester (3H-PMA) binding assay (performed at 4 degrees C). Within 2 h of
      UVA irradiation, three peaks of increased 3H-PMA binding to the ChL cells (by 70
      100%) were observed at ca. 20, 60 and 95 min post-irradiation. The exposure of
      ChL to UVA caused also a rapid, but transient, decline in the cell proliferation
      rate (by 18% within 24 h). However, the statistically significant decrease in
      cell numbers was observed only 3 days later (down by 22%). The inhibition of ChL
      proliferation was not due to alteration of cell viability as determined by trypan
      blue exclusion assay, and neither was it caused by cell cycle arrest or
      apoptosis, as determined by flow cytometry analysis of propidium iodide-labelled
      cells and cell morphology in May-Grunvald-Giemsa-stained cell smears. Phorbol
      ester-induced activation of PKC (performed at 37 degrees C) caused inhibition of
      ChL proliferation similar to that caused by UVA. This suggests that a UVA-induced
      increase of the membrane-bound fraction of PKC may be responsible for the UVA
      induced inhibition of ChL proliferation.

PMID- 8555013
TI  - Opposing effects of ultraviolet B irradiation on interleukin-1 receptor
      antagonist and interleukin-1 alpha messenger RNA expression in a human epidermoid
      carcinoma cell line.
AB  - Interleukin-1 receptor antagonist (IL-1RA) is a cytokine that acts to antagonize
      IL-1 activity without agonist function. The expression of IL-1RA has been
      reported in many cell types, including the keratinocyte that covers the outer
      most part of the skin. However the modulation of IL-1RA by ultraviolet B (UVB),
      which is the most biologically active UV, has not been reported yet. We therefore
      selected a keratinocyte cell line with a cytokine-producing profile similar to
      that of keratinocytes and tested the effect of UVB on its ability to produce IL
      1RA mRNA. IL-1RA mRNA was constitutively expressed in the cell line and began to
      be suppressed by 3 h after the UVB irradiation with 100 mJ/cm2. The level of IL
      1RA expression became lowest by 16 h after the irradiation with 100 mJ/cm2.
      Simultaneously, IL-1 alpha mRNA started to increase by 1 h and peaked by 3-16 h
      after the irradiation with 10-100 mJ/cm2. The differential expression of IL-1
      alpha and IL-1RA mRNA following exposure to a high dose (100 mJ/cm2) of UVB may
      markedly potentiate the role of IL-1 in UV-induced inflammation.

PMID- 8555014
TI  - Oxidative defense in cultured human skin fibroblasts and keratinocytes from sun
      exposed and non-exposed skin.
AB  - Skin fibroblasts and keratinocytes cultivated from chronically light-exposed skin
      sites have higher levels of the protective protein ferritin than cells derived
      from unexposed areas of the body, suggesting an adaptive response of cells
      exposed to chronic external insults. In the same line, ferritin levels were
      always found to be 2- to 7-fold higher in epidermal keratinocytes than in the
      underlying dermal fibroblasts of the same person thus providing the keratinocyte
      with continuous protection by the higher cellular ferritin content. The
      activation of ferritin by oxidative stress including UVA radiation could
      represent an important cellular defense mechanism that operates in human skin.
      Following low fluences of UVA radiation (2-4 x 10(5) J/m2), ferritin levels
      increased by 20-30% in normal adult skin fibroblasts and showed a subsequent
      decrease at higher UVA fluences. In contrast, skin keratinocytes were not
      perturbed by UVA radiation exposure except for very high fluences (1.25 x 10(6)
      J/m2) where slight decreases in cellular ferritin were noted in 7 of the 12 cell
      lines. Fibroblasts derived from light-exposed skin sites that possessed higher
      levels of cellular ferritin were highly protected against UVA-induced membrane
      damage as measured by lactate dehydrogenase release compared with fibroblasts
      from nonexposed body sites with lower levels of ferritin. It is clear from our
      results that ferritin plays an important role in protection at the cellular level
      in human skin cells, but the role of this putative protective protein in vivo
      remains to be defined.

PMID- 8555015
TI  - Chrysiasis revisited: a clinical and pathological study.
AB  - Chrysiasis is a distinctive and permanent pigmentation of light-exposed skin
      resulting from the administration of parenteral gold salts. We report a study of
      40 Caucasian patients with rheumatoid arthritis, treated with intramuscular
      sodium aurothiomalate, of whom 31 had chrysiasis. Visible changes develop above a
      threshold, equivalent to 20 mg/kg gold content, and their severity depends upon
      cumulative dose. Focal aggregates of particulate gold are deposited in the
      reticular and papillary dermis in amounts that correlate with the degree of
      pigmentation. Characteristically, initially the periorbital region is affected by
      a mauve discoloration, which intensifies and deepens into a blue/slate-grey
      colour, while extending to involve the face, neck and upper limbs. Although
      chrysiasis develops insidiously and patients may be unaware of the changes,
      positive identification is important in order to avoid misdiagnosis and medical
      mismanagement, and afford appropriate reassurance. Prevention is difficult, but
      measures to reduce sunlight exposure may be helpful.

PMID- 8555016
TI  - Topical stratum corneum lipids accelerate barrier repair after tape stripping,
      solvent treatment and some but not all types of detergent treatment.
AB  - Topical acetone treatment extracts lipids from the stratum corneum, and disrupts
      the permeability barrier, resulting in a homeostatic response in the viable
      epidermis that ultimately repairs the barrier. Recently, we have developed an
      optimal lipid mixture (cholesterol, ceramide, palmitate and linoleate
      4.3:2.3:1:1.08) that, when applied topically, accelerates barrier repair
      following extensive disruption of the barrier by acetone. The present study
      determined if topical treatment with this optimal lipid mixture would have
      beneficial effects following disruption of the barrier by petroleum ether, tape
      stripping, or by detergent treatment. Also, we determined if barrier repair was
      accelerated after moderate disturbances of barrier function. Following moderate
      or extensive disruption of the barrier by acetone or petroleum ether (solvents),
      or tape stripping (mechanical), application of the optimal lipid mixture
      accelerated barrier repair. Additionally, following barrier disruption with N
      laurosarcosine free acid or dodecylbenzensulphuric acid (detergents), the optimal
      lipid mixture similarly accelerated barrier repair. However, following disruption
      of the barrier with different detergents, sodium dodecyl sulphate and ammonium
      lauryl sulphosuccinate, the optimal lipid mixture did not improve barrier
      recovery. Thus, the optimal lipid mixture is capable of accelerating barrier
      repair following disruption of the barrier by solvent treatment or tape stripping
      (mechanical), and by certain detergents such as Sarkosyl and
      dodecylbenzensulphuric acid. The ability of the optimal lipid mixture to
      accelerate barrier repair after both moderate and extensive degrees of barrier
      disruption suggests a potential clinical use for this approach.

PMID- 8555017
TI  - Protein kinase C inhibits human hair follicle growth and hair fibre production in
      organ culture.
AB  - In this study we have used a human hair follicle whole-organ culture system to
      examine the effects of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a potent
      activator of protein kinase C (PKC), on hair follicle growth and hair fibre
      production. Anagen hair follicles were isolated from human facial skin by
      microdissection and placed in suspension culture in supplemented Williams E
      medium. Hair follicle and hair fibre lengths were measured daily using an
      inverted microscope and cumulative growth values were calculated. Treatment with
      TPA resulted in a potent, dose-dependent inhibition of total cumulative hair
      follicle growth (IC50 = 1 nM). Hair follicles grew at a comparable rate for 4
      days in the presence or absence of 10 nM TPA, after which growth of TPA-treated
      follicles ceased while control follicles grew by a further 0.8 mm over the
      subsequent 6 days. In contrast, 10 nM TPA treatment did not affect hair fibre
      elongation for a period of 8 days, after which TPA-treated fibre production
      ceased while control fibres grew by a further 0.79 mm over the subsequent 7 days.
      Incubation of hair follicles with TPA resulted in a 41% inhibition of hair fibre
      protein synthesis, as measured biochemically from the incorporation of 3H-leucine
      using a differential akali extraction method. The inhibitory effect of TPA on
      follicle growth was partially prevented by preincubation with the selective PKC
      inhibitor H-7, and almost completely prevented by preincubation with the more
      potent PKC inhibitor Ro 31-7549. Neither agent alone significantly affected
      follicle growth at concentrations that reversed the TPA response. These findings
      indicate that PKC is a negative regulator of hair follicle growth, and suggest
      that PKC may play a part in the transduction of follicular growth-inhibitory
      signals.

PMID- 8555018
TI  - HIV disease and Malassezia yeasts: a quantitative study of patients presenting
      with seborrhoeic dermatitis.
AB  - Seborrhoeic dermatitis (SD) is a disease that affects 1-3% of the general
      population, 3-5% of young adults and 20-83% of patients with AIDS. Malassezia
      yeasts have been associated with the pathogenesis of this condition. The
      association between the Malassezia yeasts and HIV-related SD is still a
      controversial subject. The objective of our study was to investigate the role of
      Malassezia yeasts in the pathogenesis of SD in the HIV population comparing the
      number of yeasts' cells with the severity of the disease and degree of
      immunosuppression. We used two quantitative counting methods: direct counting
      with Sellotape-stripped skin and recovery of the yeasts in culture using contact
      plates. This investigation has demonstrated that there is a trend between numbers
      of yeasts present on lesional skin, severity of SD and CD4-positive T lymphocytes
      count in HIV-positive patients. No quantitative differences were observed between
      HIV-related and non-HIV related SD.

PMID- 8555019
TI  - The prevalence of onychomycosis in Finland.
AB  - Few studies have been made of the prevalence of onychomycosis among ordinary
      people. We therefore investigated 800 people aged between 6 and 80 years, in
      different age groups. We found 162 persons in whom onychomycosis was clinically
      suspected. However, only the 91, in whom the fungal culture was positive for
      dermatophytic fungi, were included in the final prevalence numbers. We found a
      prevalence of 13.0% in men, 4.3% in women, and 8.4% in the entire population
      including children. Onychomycosis was not found in any of the 200 people aged
      less than 20 years. The prevalences found in this study are much higher than
      those reported in the earlier studies made elsewhere in Europe.

PMID- 8555020
TI  - Local cold exposure test as therapy control in patients with Raynaud's
      phenomenon: comparison between laser Doppler fluxmetry and simultaneous red blood
      cell velocity measurements in nailfold capillaries.
AB  - Synchronous measurement of laser Doppler flux (LDF) and capillary red blood cell
      velocity (CBV) was performed in adjacent areas of the same nailfold during a
      local cold stress test in 12 healthy controls (eight women and four men) and in
      22 patients (17 women and seven men) with secondary Raynaud's phenomenon before
      and after treatment. Two questions were addressed: Are there any differences in
      the signal pattern between LDF and RBV? Is it possible to detect early on in
      therapy, before clinical benefit becomes obvious, whether a treatment is
      successful or not? Despite the fact that the resulting signal patterns recorded
      by these two techniques are widely compatible, certain differences could be
      observed. In healthy controls, decrease of values during cooling time and
      increase after cooling were more distinct in RBV than in LDF. Compared with
      control values, CBV and LDF in patients with Raynaud's phenomenon were lower.
      After cooling CBV took an average of 3 min to reach initial value again as
      compared with 40 s in healthy controls. During 4 min observation time, pretest
      values of LDF were not achieved again in patients, whereas it took 50 s in
      healthy controls. If, after a few days of vasospasmolytic therapy, test results
      improved or normalized, clinical symptoms subsided gradually during the next
      weeks. Clinical improvement was not observed in those patients in whom cutaneous
      blood flow remained decreased despite therapy. CBV indicated this more clearly
      than LDF. Duration of flow stop at the end of cooling showed a marked improvement
      in patients treated successfully. Discrepancies between CBV and LDF are
      interpreted as being due to LDF detecting other vessels in addition to the
      superficial, nutritional capillaries. LDF seemed to be a poor tool for evaluating
      the effect of treatment. Determination of CBV and flow stop duration during local
      cold exposure may help in early selection of the best treatment for a patient
      with Raynaud's phenomenon by predicting later possible clinical benefit.

PMID- 8555021
TI  - Increased expression of lysyl oxidase in skin with scleroderma.
AB  - Lysyl oxidase initiates cross-linkage of collagen and elastin by catalysing the
      formation of a lysine-derived aldehyde. In order to study cross-linking in
      scleroderma, we used monoclonal antibodies to lysyl oxidase to determine the
      localization of this enzyme in systemic and localized scleroderma, and compared
      the distributions obtained with that in normal skin. Using an indirect
      immunofluorescent antibody method and an avidin-biotinylated enzyme complex
      method, 11 cases of diffuse type of systemic scleroderma and seven cases of
      localized scleroderma were studied. In the oedematous stage of systemic
      scleroderma, intracellular and extracellular lysyl oxidase were remarkably
      increased in the dermis, particularly in groups around blood vessels. In the
      sclerotic stage of systemic scleroderma, lysyl oxidase was detected
      intracellularly in fibroblasts and extracellularly among collagen bundles between
      the lower dermis and the subcutaneous fat tissue. In localized scleroderma, a
      marked increase in lysyl oxidase was observed in mononuclear cells and
      fibroblasts near blood vessels in the lower dermis and in the subcutaneous fat
      tissue, in addition to the extracellular deposits between collagen bundles. The
      increase in lysyl oxidase in localized scleroderma was much more common than in
      the oedematous stage of systemic scleroderma. These findings indicated that
      intracellular and extracellular expression of lysyl oxidase expression was
      greater in sclerodermatous skin than in normal skin.

PMID- 8555022
TI  - Impaired sweating as an exocrine manifestation in Sjogren's syndrome.
AB  - To examine the prevalence of hypohidrosis and to quantitate sweating as an
      exocrinopathy in Sjogren's syndrome (SS), 49 patients with SS (primary form, 38;
      secondary form, 11) were studied. Sweating was induced by mental stimulation such
      as deep breathing or hand grasping. Statistically significant reductions of sweat
      volume were seen in SS (P < 0.005). Patients under 50 years old showed impaired
      sweat function compared with normal controls (P < 0.0005). In a control study,
      only haemodialysis patients showed impairment of sweating and this was greater
      than in patients with SS aged under 50 years. These results suggest that patients
      with SS develop impaired sweating as an exocrine manifestation in addition to the
      known symptoms of xerostomia and xerophthalmus.

PMID- 8555023
TI  - Migratory properties and functional capacities of human skin dendritic cells.
AB  - The different cell types which migrated 'spontaneously' out of human skin
      explants during different periods of culture were characterized. Before culture,
      CD1a+ dendritic cells were observed not only in the epidermis but also in the
      dermis, whereas CD1b+ dendritic cells were present exclusively in the dermis. The
      populations of migrating cells were harvested and phenotyped on 3 successive days
      of culture. They always contained high percentages of CD1a+ cells. The other
      cells that migrated were T cells and macrophages. A relatively high proportion of
      the CD1a+ cells that migrated during the first 24 h culture period was also
      CD1b+. The number of cells which were positive for both CD1a and CD1b decreased
      in the following 2 days of culture. However, the purified CD1a+ cell populations
      isolated on the 3 consecutive days did not show any difference in their capacity
      to stimulate allogeneic T cells. The CD1a+ cells possess potent allo-activating
      capacities that are independent of whether or not they are positive for CD1b+.
      Three days after culture about half of the CD1a+ cells were still present in the
      epidermis and dermis, but no CD1b+ cells could be detected in the dermis. This
      suggests that the CD1b+ cells represent a population of active migrating cells.

PMID- 8555024
TI  - Urocanic acid isomers in human skin: analysis of site variation.
AB  - Urocanic acid (UCA) is found in the stratum corneum as the trans-isomer and, on
      ultraviolet (UV) irradiation, photoisomerization into cis-UCA takes place. Cis
      UCA has been suggested to play a part in UV-induced immunosuppression. In the
      present study, the concentration of UCA and the percentage as cis-UCA at 10
      different body sites of 20 normal volunteers were analysed. A large
      interindividual variation in total UCA concentration was found, but the mean UCA
      concentration in each site was similar, other than at the sole of the foot. There
      was little variation in the UCA content between sites normally exposed, and not
      exposed, to light, but the percentage of UCA in the cis form was clearly higher
      at exposed areas.

PMID- 8555025
TI  - Junctional epidermolysis bullosa and pyloric atresia: a distinct entity. Clinical
      and pathological studies in five patients.
AB  - Junctional epidermolysis bullosa (JEB) associated with pyloric atresia (PA) is a
      distinct entity which is inherited as an autosomal recessive disorder. We
      describe five patients with this association; four died in the neonatal period
      and one is still alive at 4 years of age. The cutaneous lesions in these patients
      are identical or similar to those in other JEB subtypes. Urinary tract
      involvement is part of the syndrome and presents a problem for long-term
      survival. Using the monoclonal antibody GB3 we investigated skin biopsies from
      three of our patients and showed normal expression in all of them, unrelated to
      the outcome of their disease. This indicates that the GB3 monoclonal antibody is
      without prognostic significance in this syndrome. It is clear that JEB with PA is
      a distinct entity. The molecular basis as yet is unknown.

PMID- 8555026
TI  - Prognostic value of Ki67 antigen expression in basal cell carcinomas.
AB  - Recurrence of basal cell carcinoma (BCC) following treatment is a common event
      and long-term follow-up of all patients presenting with a primary BCC has been
      recommended. Proliferation indices have been recognized as important prognostic
      factors in several tumour types in a variety of cancer systems, being
      significantly elevated in more aggressive lesions. We have examined 51 BCCs (17
      non-recurrent tumours [group 1], 17 original tumours which later recurred [group
      2-O], and the corresponding 17 recurrent specimens [group 2-R]) for Ki67 antigen
      expression, a proliferation-associated antigen using immunohistochemistry with
      the monoclonal antibody MIB1. There was a significant increase in the percentage
      positive for MIB1 in the Group 2-O as compared with the group 1 BCCs (P < 0.05).
      p53 protein expression, as assessed by immunohistochemistry with the monoclonal
      antibody DO7, was similar in each group. These results show that Ki67 antigen
      expression differs between BCCs which later recur and BCCs that do not recur.

PMID- 8555027
TI  - Characterization of the aminopeptidase activity of epidermal leukotriene A4
      hydrolase against the opioid dynorphin fragment 1-7.
AB  - Leukotriene A4 hydrolase is a bifunctional cytosolic enzyme, which both
      hydrolyses leukotriene A4 (LTA4) into leukotriene B4 (LTB4) and exerts
      aminopeptidase activity against opioid peptides. In the present study we have
      investigated whether the peptides angiotensin I and II, bradykinin, kallidine,
      histamine, dynorphin fragment 1-7 and substance P can act as substrates for
      epidermal and neutrophil LTA4 hydrolase. Among the tested substrates, dynorphin
      fragment 1-7 was found to be the best substrate for the enzyme. The
      aminopeptidase activity of epidermal and neutrophil LTA4 hydrolase against
      dynorphin fragment 1-7 was further characterized. The enzyme was purified from
      human epidermis and human neutrophils by anion exchange chromatography (Q
      Sepharose) and affinity chromatography on a column with the LTA4 hydrolase
      inhibitor bestatin coupled to AH-Sepharose. The incubation of the dynorphin
      fragment 1-7 with LTA4 hydrolase resulted in the formation of tyrosine. The
      presence of the N-terminal amino acid tyrosine is essential for the interaction
      of opioids with their receptors, and this finding indicates that the LTA4
      hydrolase can inactivate dynorphin fragment 1-7. After the two purification steps
      no other aminopeptidases acting at the N-terminal tyrosine of dynorphin fragment
      1-7 was present in the preparation. This was demonstrated by the abolishment of
      the degradation at the N-terminal end of dynorphin fragment 1-7 when
      preincubating the enzyme preparation with LTA4 before the incubation with the
      dynorphin fragment 1-7. The abolishment of the aminopeptidase activity shows that
      activation of the hydrolase part of the enzyme, with conversion of LTA4 into the
      potent proinflammatory compound LTB4, results in an inhibition of the
      aminopeptidase activity of the enzyme. As a result, the catabolism of dynorphin
      fragment 1-7 and probably of other opioid peptides is inhibited, resulting in
      sustained biological effects of these opioids. This phenomenon may be important
      for the maintenance of inflammation in skin conditions, such as psoriasis and
      atopic dermatitis, in which LTB4 is formed.

PMID- 8555028
TI  - Cytokine-mediated effects of peripheral blood mononuclear cells from patients
      with atopic eczema on keratinocytes (HaCaT) in a new coculture system.
AB  - Interactions between keratinocytes and mononuclear cells via cytokines and
      adhesion molecules are thought to play a crucial part in inflammatory skin
      diseases. The cytokine-mediated effects of peripheral blood mononuclear cells
      (PBMC) from patients with atopic eczema (AE) and healthy individuals on
      keratinocytes (HaCaT) were investigated in vitro. A new coculture model
      (Transwell system) which consists of a lower and an upper compartment, which are
      separated by a polycarbonate-treated membrane, was established. 3[H]thymidine
      incorporation of keratinocytes and lymphocytes, as well as IL-6, IL-8 and IFN
      gamma synthesis, were measured. Keratinocyte proliferation was significantly
      enhanced in the presence of PBMC from patients with AE. In contrast, PBMC from
      normal donors did not enhance HaCaT cell proliferation when they were cocultured.
      Lymphocytes from patients with AE showed a significantly enhanced proliferation
      after coculture with keratinocytes. However, PBMC from normal donors did not
      proliferate in the presence of HaCaT cells. Keratinocyte supernatants incubated
      with PBMC from either atopic or normal volunteers induced a suppression of
      lymphocyte 3[H]thymidine incorporation. In supernatants from cocultures of PBMC
      from patients with AE and keratinocytes, significantly enhanced amounts of IL-6
      and IL-8, compared with normal donor's lymphocytes and HaCaT cells, were
      measured. No differences in IFN gamma production were observed. When PBMC were
      cultured without HaCaT cells, supernatants contained equal levels of IL-6, IL-8
      and IFN-gamma in normal donors and in patients with AE. Interestingly, HaCaT
      cells spontaneously secrete measurable amounts of IL-6, IL-8 and IFN-gamma.
      Blocking experiments with neutralizing antibodies against these interleukins
      showed a complete inhibition of keratinocyte proliferation when PBMC from normal
      donors were used whereas the proliferative potency of PBMC supernatants from
      patients with AE on keratinocytes remained. Our data indicate that (i) PBMC from
      patients with AE stimulate keratinocyte proliferation via soluble factor(s) that
      are different from IL-6, IL-8 and IFN-gamma; (ii) probably, HaCaT cells
      spontaneously produce lymphocyte/monocyte inhibitory soluble factors and IL-6, IL
      8 as well as IFN-gamma; and (iii) secretion and/or activity of keratinocyte
      derived inhibitory mediators is regulated via cytokines of PBMC infiltrating
      inflammatory skin.

PMID- 8555029
TI  - Differentiation and CD23 expression of peripheral blood monocytes in patients
      with atopic dermatitis.
AB  - In this study we investigate the expression of the low affinity immunoglobulin E
      (IgE) receptor (Fc epsilon RII) on plastic-adherent leucocytes from patients with
      atopic dermatitis (AD). Peripheral blood mononuclear cells were obtained from
      patients with AD, normal controls (and in one study from a group of atopic
      asthmatic patients). Monocytes were separated by 2-h adherence to plastic. These
      cells were then cultured for up to 7 days. Cells were harvested at time 0 (after
      adherence), and after 5 and 7 days culture, and cytospins were prepared. The
      proportion of cells expressing the phenotype of antigen presenting cells
      (monoclonal antibodies (mAb) RFD1+), and mature phagocytes (mAb RFD7+) together
      with CD23, were evaluated using combination staining with immunoperoxidase and
      alkaline phosphatase anti-alkaline phosphatase methods. It was found that a
      significantly larger proportion of circulating adherent cells in AD patients
      expressed the RFD1 antigen, and that increases in the proportion of these
      adherent cells expressing RFD1 or RFD7 occurred faster as cells matured in
      culture, when compared with cells obtained from normal controls. By day 7,
      however, equivalent proportions of RFD1+ and RFD7+ cells were present in AD and
      control cultures. None the less, expression of the CD23 molecule was consistently
      present on a larger proportion of both RFD1+ and RFD7+ cells from AD patients
      compared with controls. The raised proportion of circulating RFD1+ cells found in
      AD was not present in samples from atopic asthmatics, while the raised expression
      of CD23 on these cells occurred in samples from both these groups. These data
      support the suggestion that abnormalities in peripheral blood adherent cell
      phenotype, maturation, and CD23 expression, occur in AD patients. Some of these
      observations may be related to atopy in general rather than being specific for
      this skin disease.

PMID- 8555030
TI  - Pyridoxine in atopic dermatitis.
AB  - A previous study has reported benefit when pyridoxine hydrochloride was given to
      patients with atopic dermatitis. To investigate this in children, we performed a
      randomized, double-blind, parallel-group, placebo-controlled trial. Forty-eight
      children with moderate or severe atopic dermatitis were recruited and, of those
      who completed the study, 19 received pyridoxine hydrochloride 50 mg once daily
      for 4 weeks and 22 received placebo. Disease activity was monitored by clinical
      severity scores measuring the extent and degrees of erythema recorded by the
      investigator and symptom scores (daytime itch and nocturnal sleep disturbance)
      recorded by parents. There was no statistically significant difference between
      the two groups at the end of treatment. We have been unable to demonstrate
      clinical benefit from pyridoxine supplementation in children with atopic
      dermatitis.

PMID- 8555031
TI  - Age at onset and different types of psoriasis.
AB  - The age at onset of psoriasis has been analysed for 11,366 psoriasis patients.
      The age at onset for siblings of probands has been analysed for 805 probands
      having one affected sibling and for 179 probands having two affected siblings.
      The age at onset curve for all probands shows a dominating maximum at about
      puberty but also indications for two more maxima at about 30 and 50 years of age,
      respectively. A more relevant picture of the risk of getting psoriasis at
      different ages is obtained if the onset for old people having psoriasis is
      investigated. The three maxima come out more clearly in this case, and the
      puberty maximum is not so dominating. For the families with one proband and two
      affected siblings there is a statistically significant correlation (P < 0.001)
      between the age at onset of the proband and of the siblings, and also between the
      siblings. The correlation coefficient is between 0.30 and 0.45. For the probands
      with one affected sibling, the ages at onset of the siblings mainly fall in the
      same range as those of the probands. These data indicate three groups of patients
      with respect to age at onset. However, the overlap between the different groups
      is considerable. The data presented are compatible with three, possibly
      genetically different, variants of psoriasis vulgaris. By studying the occurrence
      of psoriasis among parents of the probands, the gene frequency can be estimated
      assuming a recessive mode of inheritance. It then turns out that the gene
      frequency of the group with the earliest age at onset has a gene frequency of
      about 0.25, the next earliest, 0.18, and the latest, 0.14.

PMID- 8555032
TI  - Sequential liver biopsies during long-term methotrexate treatment for psoriasis:
      a reappraisal.
AB  - One hundred and eighty-two liver biopsies were performed over a 10-year period on
      patients receiving long-term, low-dose, once weekly oral methotrexate (MTX) for
      severe psoriasis. Forty-nine patients had two or more biopsies during continued
      treatment and formed the study population for our analysis. The first and last
      biopsies were compared to determine progression of any histological
      abnormalities. Liver biopsies were assessed without knowledge of the MTX dose and
      allocated to one of five groups according to the severity of the histological
      abnormalities. These were defined as: (1) normal; (2) steatosis alone; (3)
      inflammation without fibrosis; (4) fibrosis; and (5) cirrhosis. The mean
      cumulative dose of MTX at the time of the first biopsy was 2743 mg (range 315
      10,024), given over 275 weeks (range 26-738). In the interval between the first
      and last biopsies, patients received, on average, a further 2362 mg (range 390
      7155) over 225 weeks (range 60-460). There was improvement in the histological
      assessment in 12 patients, no change in 28 patients, and deterioration in nine
      patients. None developed cirrhosis. Liver biopsy findings prompted
      discontinuation of MTX in four of the 49 patients on long-term treatment. This
      has to be weighed against the cost and morbidity of the 124 biopsies performed in
      these patients. Our results suggest that, with careful follow-up, the risk of
      development or progression of liver disease in patients receiving long-term, low
      dose, once weekly oral MTX for psoriasis is modest, and that the requirement for
      performing routine liver biopsies in these patients needs to be reconsidered.

PMID- 8555033
TI  - Anti-Ro/SSA-associated annular erythema in childhood.
AB  - We report four children with anti-Ro/SSA positive who presented with an annular
      erythema as a manifestation of Sjogren's syndrome. One patient had an aseptic
      meningoencephalitis as well as cutaneous lesions. Children with annular erythema
      should be carefully followed for features of Sjogren's syndrome, which is
      believed to be a rare condition in children.

PMID- 8555034
TI  - Dermatomyositis presenting in pregnancy.
AB  - We report the onset of dermatomyositis in a woman pregnant 38-weeks who
      subsequently delivered a healthy infant. The disease improved rapidly following
      delivery. The association of dermatomyositis with pregnancy is unusual, and fetal
      outcome may be adversely affected.

PMID- 8555035
TI  - Occupational scleroderma. A 17-year follow-up study.
AB  - Two patients with a scleroderma-like disorder induced by epoxy resins were
      reported from the Department of Dermatology, Gunma University School of Medicine,
      Japan in 1980. Here, we describe the clinical and laboratory characteristics of
      these patients after 17 years' follow-up from 1976 to 1993. Their systemic
      manifestations and indurated sclerotic skin changes disappeared within 5 years.
      No internal organ involvement has developed during the period of follow-up. On
      routine laboratory tests, no abnormalities have been found in the peripheral
      blood or in the blood chemistry or serology. Histological examination revealed
      atrophy of the dermis and restoration of the normal pattern of fine collagen
      bundles, when compared with the previous skin biopsy specimens. This scleroderma
      like disorder induced by epoxy resins is considered to be different from systemic
      sclerosis: it has an acute onset and a fairly good prognosis, and does not show
      involvement of the internal organs.

PMID- 8555036
TI  - Vasculitis in a fixed drug eruption due to paracetamol.
AB  - A 48-year-old man presented with a history of recurrent erythematous lesions on
      the trunk and limbs. Examination suggested a fixed drug eruption and this was
      confirmed by oral challenge with paracetamol. The histology was unusual as it
      showed a leucocytoclastic vasculitis. Patients may have difficulty avoiding the
      offending drug because many drugs bought over the counter have similar names but
      different constituents. In addition, it may be difficult to persuade the patient
      that a specific drug is responsible for their skin problem.

PMID- 8555037
TI  - Progesterone-induced urticaria--need it be autoimmune?
AB  - A patient with persistent urticaria related to the premenstrual phase of the
      menstrual cycle is presented. Although systemic administration of progesterone
      provoked the eruption, we were unable to confirm that there was an immunological
      reaction to endogenous progesterone or oestrogen. Mechanisms whereby progesterone
      can augment subclinical types I and IV hypersensitivity reactions are discussed.

PMID- 8555039
TI  - Odonto-onycho-dermal dysplasia.
AB  - Odonto-onycho-dermal dysplasia is an ectodermal dysplasia (ED) described once
      previously in two families who exhibited atrophic malar patches, sparse hair,
      conical teeth, dystrophic nails and hyperkeratosis of the palms and soles. We
      describe a boy who developed a blistering malar rash soon after birth. When
      examined at 11 months, and then at 27 months of age, he had persistent atrophic
      malar plaques that reddened with heat. He also showed nail dystrophy, sparse
      hair, lingual concavity of the incisors, a bifid maxillary incisor, a five-cusped
      molar, and hyperhidrosis of the palms and soles. In addition he had chronic
      tearing, photophobia, blepharitis, and a mild keratitis. After reviewing EDs with
      atrophic or scar-like skin changes, we believe this child most resembles the
      patients with odonto-onycho-dermal dysplasia, although his eye findings are
      unique.

PMID- 8555038
TI  - Eruptive pyogenic granulomas: a successfully treated patient and review of the
      literature.
AB  - Pyogenic granuloma, also known as lobular capillary haemangioma, is a solitary,
      benign vascular skin tumour. Although a single pyogenic granuloma is common,
      multiple eruptive pyogenic granulomas are extremely rare. We report the
      occurrence of multiple, eruptive pyogenic granulomas in a previously healthy 17
      year-old girl. Over 200 lesions appeared spontaneously over an 8-month period.
      Lesions were initially treated with cryotherapy, and then with the pulsed dye
      laser, resulting in their complete clearance.

PMID- 8555040
TI  - A papular eruption secondary to infection with Corynebacterium jeikeium, with
      histopathological features mimicking botryomycosis.
AB  - Corynebacterium jeikeium has been increasingly recognized as a pathogen,
      particularly in immunocompromised patients and in those with a prosthetic heart
      valve. Although cutaneous manifestations of C. jeikeium infection have been
      described, we have only found two case reports that give an histological
      description of the lesions. We present three patients with haematological
      malignancies who developed infection with C. jeikeium and a papular eruption.
      Skin biopsy disclosed similar histological features in all three patients, namely
      numerous Gram-positive bacteria enclosed in an eosinophilic matrix, with a
      minimal inflammatory response. C. jeikeium was cultured from cutaneous lesions in
      two cases.

PMID- 8555041
TI  - Scedosporium apiospermum infection imitating lymphocutaneous sporotrichosis in a
      patient with myeloblastic-monocytic leukaemia.
AB  - A 63-year-old man with a history of myeloblastic-monocytic leukaemia developed
      partly suppurating cutaneous nodules on the lower left leg. The nodules proceeded
      to spread in a linear fashion up the limb, following the line of the lymphatic
      drainage. Mycological examination of a skin biopsy demonstrated Scedoporium
      apiospermum. This case highlights the potential for Scedosporium species to act
      as opportunistic infections in immunosuppressed humans.

PMID- 8555042
TI  - The emergence of Sezary cells during the treatment of cutaneous T-cell lymphoma.
AB  - A 52-year-old man with cutaneous T-cell lymphoma presented with Sezary syndrome
      like features including exfoliative erythroderma, lymphadenopathy and leukaemic
      change without the presence of Sezary cells. Southern blot hybridization analysis
      revealed T-cell receptor beta-chain gene rearrangements, both in the peripheral
      blood and in the lymph node. Atypical large cells with convoluted nuclei (Sezary
      like cells) first appeared during combined chemotherapy. Although Sezary syndrome
      is characterized by its particular manifestations and the presence of Sezary
      cells in the peripheral blood, the clinical significance of Sezary cells has been
      questioned. It still needs to be decided whether or not the Sezary cell is
      malignant.

PMID- 8555043
TI  - Toxic epidermal necrolysis (Lyell syndrome) following famotidine administration.

PMID- 8555044
TI  - Terbinafine and fixed drug eruption.

PMID- 8555045
TI  - Fatal poisoning due to dapsone in a patient with grossly elevated methaemoglobin
      levels.

PMID- 8555046
TI  - Unilateral lichen planus, sparing vitiliginous skin.

PMID- 8555047
TI  - Pityriasis rubra pilaris and HIV infection: a part of the spectrum of HIV
      associated follicular syndrome.

PMID- 8555048
TI  - Reticular acropigmentation of Kitamura: a study of HLA antigen typing.

PMID- 8555049
TI  - Mucinous carcinoma of the skin.

PMID- 8555050
TI  - Autoimmune mechanisms of depletion of CD4 cells in HIV infection.

PMID- 8555051
TI  - Both early and committed haemopoietic progenitors are more frequent in peripheral
      blood than in bone marrow during mobilization induced by high-dose chemotherapy +
      G-CSF.
AB  - Haemopoietic growth factor administration following high-dose chemotherapy
      markedly amplifies progenitor cell pool in the peripheral blood (PB). Collection
      and reinfusion of these cells enable rapid haemopoietic reconstitution following
      autograft. Less is known on engraftment potentiality of bone marrow (BM) cells
      taken under analogous conditions. To investigate this tissue, PB and BM were
      evaluated simultaneously during maximal mobilization in a series of 14 patients
      undergoing the HDS chemotherapy programme. A significantly higher growth of
      committed progenitors was found from PB rather than from BM (663 +/- 123 v 267 +/
      40 CFU-GM/10(5) MNC, respectively). Also, significantly more CFU-GM could be
      collected by a median of three leukaphereses, compared to those harvested from BM
      (158 +/- 31 v 16 +/- 4 x 10(4) CFU-GM/kg, respectively). Most mobilized CFU-GM
      were phenotypically immature (CD15-); in addition, circulating cells included
      primitive progenitors, as assessed by LTC-IC assay, or by evaluation of non
      proliferating pre-CFU-GM, selected by an anti-CD71 immunotoxin. The amount of pre
      CFU-GM determined by both techniques was consistently higher in PB than in BM.
      Moreover, a direct correlation could be established between circulating CFU-GM
      and primitive precursors. Thus, during optimally induced mobilization, PB
      contains many more haemopoietic progenitors, of both committed and primitive
      stages, than does BM. Under such conditions, PB is probably the best source of
      material for graft purposes.

PMID- 8555052
TI  - The effect of human flt-3 ligand on committed progenitor cell production from
      normal, aplastic anaemia and Diamond-Blackfan anaemia bone marrow.
AB  - We investigated the effect of the human ligand for flt-3 (FL) on the committed
      progenitor colony formation of normal bone marrow (BM) (n = 9) and BM from four
      aplastic anaemia (AA) and three Diamond-Blackfan anaemia (DBA) patients.
      Methylcellulose committed progenitor cell assays were carried out using FL alone
      and in combinations with granulocyte-macrophage colony-stimulating factor (GM
      CSF), interleukin-3 (IL-3) and c-kit ligand (KL). FL alone had a limited, though
      significant, effect on the production of granulocyte-macrophage colony-forming
      unit (CFU-GM) colonies from normal BM and showed an additive effect with IL-3 and
      GM-CSF separately, but not in combination. FL did not increase the stimulation of
      KL and did not have an effect on the production of erythroid progenitor colonies.
      FL had no effect on the AA and DBA BMs studied.

PMID- 8555053
TI  - Haemopoietic growth factor production by normal and aplastic anaemia stroma in
      long-term bone marrow culture.
AB  - Defective marrow stroma, or microenvironment, have been proposed as one of
      several mechanisms to account for bone marrow failure in aplastic anaemia (AA).
      This could involve defects in positive- or negative-acting haemopoietic regulator
      expression by AA stroma, or alteration of normal stroma-stem cell interactions.
      We have used a sensitive bioassay to investigate production of granulocyte-colony
      stimulating factor (G-CSF), granulocyte-macrophage-colony stimulating factor (GM
      CSF), interleukin (IL)-3, IL-6 and stem cell growth factor (SCF), by normal and
      AA stroma in long-term bone marrow culture (LTBMC). LTBMC were grown to
      confluence, irradiated and harvested to yield a single cell suspension. These
      cells were cocultured with normal target bone marrow mononuclear cells (BMMC), or
      CD34+ cells, in clonogenic assays, in the absence of exogenous cytokines.
      Cytokines responsible for the colony-stimulating activity (CSA) and burst
      promoting activity (BPA) produced by stromal cells were identified by
      neutralizing antibodies to specific cytokines. All normal stroma populations
      produced G-CSF and GM-CSF, 93% produced IL-3, 80% produced IL-6, and 70% produced
      SCF. Similarly, all AA stroma produced G-CSF and GM-CSF, and 71% produced SCF. In
      contrast, only 71% of AA stroma produced IL-3 and 36% produced IL-6. Target cell
      stimulation was not dependent on direct stroma-target cell contact, suggesting
      production of soluble cytokines. However, although both IL-6 and G-CSF were
      detected in LTBMC supernatants by enzyme-linked immunoassay (ELISA), IL-3 and GM
      CSF were undetectable, perhaps indicating low-level local production of these
      factors.

PMID- 8555054
TI  - Correlation between a sandwich ELISA and an in-vitro bioassay for erythropoietin
      in human plasma.
AB  - A sandwich-type enzyme-linked immunosorbent assay (ELISA) for human
      erythropoietin (EPO) using two anti-EPO monoclonal antibodies has been compared
      with an in-vitro EPO bioassay based on CFU-E colony formation in fetal mouse
      liver cell cultures. In normal subjects and non-uraemic anaemic patients the
      plasma EPO values estimated with the ELISA correlated well with those by the
      bioassay, and also inversely with the values of blood Hb, PCV and RBC counts.
      Dose-response curves for plasma and standard recombinant human EPO in the ELISA
      were parallel to each other. These results further confirm the validity for the
      ELISA in measuring circulating human EPO.

PMID- 8555055
TI  - Tumour necrosis factor alpha-induced oxidative burst in neutrophils adherent to
      fibronectin: effects of cyclic AMP-elevating agents.
AB  - Human neutrophils, plated on fibronectin-coated polystyrene wells, were found to
      exhibit a prolonged production of superoxide anion (O2-) in response to tumour
      necrosis factor-alpha (TNF). The TNF-triggered O2- production was significantly
      reduced by 10 microM prostaglandin E2 (PGE2), which was ineffective at lower
      doses. Moreover, the O2- production was slightly reduced by the phosphodiesterase
      type IV (PDE IV) inhibitor RO 20-1724. When PGE2 and RO 20-1724 were added
      together to TNF-triggered neutrophils they caused a marked synergistic inhibition
      of O2- production. The action of PGE2 could be mimicked by forskolin (FK), a well
      known direct activator of adenylate cyclase. These results suggest that cyclic
      AMP (cAMP)-elevating agents (PGE2, FK, RO 20-1724) down-regulate the capacity of
      adherent neutrophils to mount the respiratory burst in response to TNF.
      Consistent with this interpretation, PGE2 and RO 20-1724 increased the
      intracellular levels of cAMP displaying synergistic activity. Moreover, the
      membrane-permeable analogue of cAMP, dibutyryl cAMP, was found to inhibit the TNF
      induced O2- production in a dose-dependent manner. As all the aforementioned cAMP
      elevating agents did not affect the O2- production in response to phorbol
      myristate acetate, they appear to act by interfering with the assembly of the O2(
      )-generating NADPH oxidase complex rather than by directly inhibiting the
      activity of already working oxidase complex. In conclusion, taking into account
      the TNF capacity to promote PGE2 formation at sites of inflammation, our
      observations suggest the existence of a negative PGE2-dependent feed-back,
      potentially capable of controlling the neutrophil response to TNF and susceptible
      to amplification by PDE IV-inhibiting compounds.

PMID- 8555056
TI  - Alterations of effector cell molecule expression on neutrophils in granulocyte
      colony-stimulating factor-producing tumour.
AB  - A 68-year-old man was diagnosed as having a granulocyte colony-stimulating factor
      (G-CSF)-producing mediastinal tumour. Mediastinotomy was performed, and
      thereafter the elevated leucocyte count and serum G-CSF concentration returned to
      the normal range. The surface expression of effector cell molecules on
      neutrophils was serially examined. Before operation, the expression of FcRI and
      CR1 was increased but the expression of FcRIII and L-selectin was reduced in the
      patient. The altered expression of these molecules returned to the normal levels
      after operation. These findings suggest that G-CSF produced by the tumour
      modulated neutrophil effector cell molecule expression in the patient.

PMID- 8555057
TI  - A simple method for synthesis of B-cell clonospecific probes.
AB  - A sensitive PCR-based method was developed to produce B-cell clonogenic probes
      without the need for sequencing and specific oligonucleotide synthesis.
      Specificity and sensitivity were assessed and found to be comparable to that
      achieved using established methods. Possible applications include the detection
      of MRD, bone marrow involvement with lymphoma, and the contamination of
      autologous bone marrow or peripheral blood progenitor cell harvests with
      malignant cells carrying IgH rearrangements.

PMID- 8555058
TI  - Glucosamine 6-phosphate deaminase in Plasmodium falciparum.
AB  - The pathways of glucose utilization for energy production in the malaria
      parasite, Plasmodium falciparum, have been studied extensively. Little is known,
      however, about the reactions by which glucose is converted into complex
      carbohydrates in the parasite, and knowledge of the catabolism of these
      substances is likewise scanty. The present investigation was undertaken to
      determine whether the parasites possess a key enzyme of glucosamine catabolism,
      i.e. glucosamine 6-phosphate deaminase (EC 5.3.1.40), which catalyses the
      conversion of the sugar phosphate to fructose 6-phosphate and ammonia. Lysates of
      Plasmodium-infected erythrocytes had substantially higher deaminase activity than
      control samples from normal erythrocytes, and an even higher specific activity
      was observed in extracts of isolated parasites, amounting to 20-40 times that of
      uninfected cells. Anion exchange chromatography indicated that the parasite
      deaminase eluted in a retarded position when compared to the elution profile of
      the erythrocyte enzyme. The charge difference suggested by these findings was
      established more directly by chromatofocusing, which indicated pI values of 6.85
      and 8.55 for the parasite and erythrocyte deaminases, respectively. Other
      differences were also observed, notably a greater thermolability on the part of
      the parasite enzyme. These results indicated that the parasites synthesize a
      specific deaminase that is distinct from the normal erythrocyte enzyme. Studies
      on synchronized parasite cultures further indicated that the parasite deaminase
      is developmentally regulated, because a dramatic increase in activity levels
      occurred during the later stages of parasite development.

PMID- 8555059
TI  - The glycosylation of red cell autoantibodies affects their functional activity in
      vitro.
AB  - Factors governing the functional activity of red cell autoantibodies are poorly
      defined. Here we report the presence of qualitative differences in the
      glycosylation of IgG autoantibodies which affect in vitro interactions with Fc
      gamma RIII. The following antibodies were affinity-purified by adsorption and
      elution from normal red cells: IgG eluted from the red cells of 27 haemolysing or
      non-haemolysing patients, anti-D in sera from 11 pregnant women, and IgG1 and
      IgG3 human monoclonal anti-D. Monoclonal antibodies with differing levels of
      agalactosyl IgG were produced by culturing cell lines at high or low cell
      density. The % IgG with oligosaccharides lacking terminal galactose residues
      (agalactosyl IgG) of antibodies was designated as low, medium or high according
      to their reactivity with a monoclonal antibody to terminal N-acetylglucosamine.
      Fc gamma RIII-mediated functional activity was assessed by measuring the K-cell
      mediated lysis of red cells in eluates diluted to achieve comparable levels of
      red cells sensitization. All eluates containing allo-anti-D were lytic (range 74
      100%). In contrast, lysis by autoantibodies varied from 0 to 100%; 11/13 eluates
      from red cells of haemolysing patients promoted > 5% lysis compared to 2/7
      eluates from red cells of non-haemolysing patients (P < 0.02). The ability of
      autoantibodies to promote K-cell-mediated red cell lysis correlated inversely
      with their level of agalactosyl IgG (r = -0.56, P < 0.01, n = 23). Further,
      monoclonal anti-D antibodies with very low levels of agalactosyl IgG were
      comparatively more lytic than the same antibodies containing more agalactosyl
      IgG. Analysis of the ratio of kappa:lambda light chains suggested that
      autoantibodies from 6/19 patients were monoclonal or oligoclonal in nature. The
      data indicate that IgG red cell autoantibodies from different patients are
      functionally heterogenous, and that this may be due, at least in part, to
      qualitative differences in the Fc region glycosylation reflected by differences
      in the proportion of agalactosyl IgG. This heterogeneity is consistent with the
      clonally-restricted nature of the autoantibodies in some patients.

PMID- 8555060
TI  - Hb Arta [beta 45 (CD4) Phe-->Cys]: a new unstable haemoglobin with reduced oxygen
      affinity in trans with beta-thalassaemia.
AB  - The interaction of rare Hb variants with beta(0)-thalassaemia results in a
      quasihomozygous state where the erythrocytes contain the variant as the only
      major adult Hb component. Such a situation is a unique model that enables
      functional studies even in the case of a neutral variant that could not be
      isolated from Hb A. We report here an unusual patient carrying Hb Arta, a novel
      Hb variant [beta 45 (CD4) Phe-->Cys], in trans with beta(0)-thalassaemia gene
      (beta(0) 39). The aminoacid substitution at the critical CD corner of this Hb
      molecular renders the molecule unstable. In addition, haem is displaced in a
      position that favours the deoxy (T) conformation of the variant, but less than in
      Hb Cheverly [beta 45 (CD4) Phe-->Ser], and results in a p50 of 43 mmHg (pH 7.4,
      37 degrees C) in the red cells with preservation of cooperativity. Solution
      studies of the almost pure Hb Arta show a 50% decrease in oxygen affinity and
      normal cooperativity; the Bohr effect and the interaction with organic phosphates
      are similar to those of Hb A. Hb Arta retains both normal homo- and heterotropic
      effects allowing a well-preserved oxygen transport in vivo despite a mild
      anaemia.

PMID- 8555061
TI  - Rapid diagnosis of beta-thalassaemia by mutagenically separated polymerase chain
      reaction (MS-PCR) and its application to prenatal diagnosis.
AB  - We have developed a rapid and simple PCR-based method which is modified from the
      mutagenically separated polymerase chain reaction (MS-PCR) to detect the
      molecular defects of beta-thalassaemia. We can use this technique to amplify
      normal and mutant alleles of the beta-globin gene in the same reaction tube,
      using different-sized allele-specific primers. This mutagenesis separates the
      amplification reactions of alleles performed in the same tube. Subsequent gel
      electrophoresis shows at least one of the two allelic products at the same locus
      or at least two of the several allelic products at different loci. Therefore, in
      addition to simple handling, MS-PCR provides a within-assay quality control for
      the exclusion of false negative results. The five most common mutations of beta
      thalassaemia and haemoglobin E which occur in the Taiwanese population were
      tested, and 14 prenatal samples were checked with accurate results. This method
      is simple, rapid and accurate, and can be used routinely in prenatal diagnosis.
      The principle used here can also be applied to other genetic diseases.

PMID- 8555062
TI  - A new alpha chain variant Hb Sallanches [alpha 2 104(G11) Cys-->Tyr] associated
      with HbH disease in one homozygous patient.
AB  - We identified a new alpha-chain variant (alpha Sal) associated with haemolytic
      anaemia and low level of HbH in one homozygous patient. This new mutation is
      located in codon 104 (TGC-->TAC) of the alpha 2 globin gene and results in a Cys-
      >Tyr replacement. In vitro and in vivo biosynthetic studies suggest that the
      mechanism leading to HbH disease in this homozygous patient is mostly related to
      a significant instability of alpha Sal:beta dimers rather than to the
      hyperinstability of the alpha Sal chain itself only.

PMID- 8555063
TI  - Hypocellular myelodysplastic syndromes (MDS): new proposals.
AB  - To determine whether hypocellular MDS differs from normo/hypercellular MDS, we
      attempted to identify hypocellular MDS cases either by correcting the bone marrow
      (BM) cellularity by age (28 patients) or by using a single arbitrary value of BM
      cellularity (25 patients) and compared these two groups of hypocellular cases to
      the normo/hypercellular MDS cases (72 patients). 18 patients were common to both
      hypocellular groups. Patients with hypocellular MDS in both of these selected
      groups have similar features with regard to age and sex distribution, peripheral
      blood and bone marrow parameters, FAB subtypes, karyotypes, leukaemic
      transformation, and survival. However, the median age of patients in < 30% BM
      cellularity group was higher than those patients in the age-corrected group (69
      years v 62 years). The selection of < 30% cellularity excluded 10 cases in the
      age group < 70 years but included another seven patients in the age group of > 70
      years. However, correction of BM cellularity by age revealed that those included
      patients (selected for < 30% cellularity) who had normocellular BM by their age.
      Therefore we recommend the age-correcting grouping to ensure comparable series
      for comparison, for response to treatment, and survival. Finally, BM cellularity
      does not appear to be an important factor on prognosis in MDS, because patients
      with hypocellular MDS in both selected groups have similar prognosis to those
      with normo/hypercellular MDS patients.

PMID- 8555064
TI  - Increased platelet CD36 constitutes a common marker in myeloproliferative
      disorders.
AB  - The distribution of the major platelet membrane glycoproteins (GP), Ib, IX, IIb
      IIIa and IV (or CD36), which play important roles as receptors for adhesive
      molecules in haemostasis and thrombosis, was studied in 34 patients with
      myeloproliferative disorders (MPD): 13 had essential thrombocythaemia (ET), 12
      had polycythaemia vera (PV) and nine had chronic myelogenous leukaemia (CML).
      Only occasionally were modifications of the numbers of GPIb or GPIIb-IIIa
      measured using the binding of specific radiolabelled antibodies to platelets. In
      contrast, 2-3-fold increases of the total CD36 content and the surface CD36
      expression were measured in almost all patients studied, using a radioimmunoassay
      and the direct binding of the radiolabelled antibody, FA6-152, to the platelet
      surface, respectively. These results indicate that the abnormality affected both
      the external and internal CD36 pools. Therefore platelet CD36 may be a useful
      tool for the diagnosis and the follow-up of MPD patients. Surface CD36 has been
      proposed as a platelet receptor for thrombospondin, an adhesive glycoprotein that
      is released from platelets upon activation and promotes aggregate formation.
      Despite a 2-fold increase of CD36 molecules, resting and thrombin-activated
      platelets from ET patients expressed the same amount of thrombospondin as normal
      platelets, suggesting that there is not a direct correlation between the CD36
      expression and thrombospondin binding either spontaneously or after activation.

PMID- 8555065
TI  - Involvement of the cyclin-dependent kinase-4 inhibitor (CDKN2) gene in the
      pathogenesis of lymphoid blast crisis of chronic myelogenous leukaemia.
AB  - Recent data suggest that homozygous deletion of the cyclin-dependent kinase 4
      inhibitor gene (CDKN2), a putative tumour suppressor gene located on chromosome
      9p21, represents a common genetic event in human cancer. As the molecular basis
      of the evolution of chronic myelogenous leukaemia (CML) into blast crisis remains
      largely unknown, we decided to investigate if the occurrence of similar deletions
      could represent one of the mechanisms underlying the disease progression. Whereas
      none of 22 chronic phase CML cases examined showed alterations, we found that
      3/17 total blast crisis examined (18%) showed a homozygous deletion of the CDKN2
      gene. The deletions were restricted to cases of lymphoid blast crisis, being
      present in 3/8 (40%) of the lymphoid and in none of the nine myeloid cases
      examined. The fact that the chronic phase DNA obtained at diagnosis in one of the
      cases lacks the homozygous deletion observed in blast crisis, suggests that the
      final deletion event took place concomitantly with the progression of the
      disease. Furthermore, the analysis of polymorphic regions on chromosome 9p21
      flanking at both sides the CDKN2 gene, showed that deletions at 9p21 differ
      between cases and are characterized by a wide range of extensions. A concomitant
      search for a possible involvement of the p53 tumour suppressor gene in the same
      series of patients showed mutations of the gene and loss of heterozygosity at 17p
      only in myeloid blast crisis, suggesting the presence of distinct molecular
      pathways in the pathogenesis of lymphoid and myeloid blast crisis.

PMID- 8555066
TI  - New type of t(14;18) in a non-Hodgkin's lymphoma provides insight in molecular
      events in early B-cell differentiation.
AB  - In this report a follicular non-Hodgkin's lymphoma (NHL) carrying an unusual
      t(14;18) is described. This translocation most likely occurred during the VH to D
      JH rearrangement process of the IgH locus. From the data combined with data from
      the literature we conclude that the chance for development of a t(14;18)
      decreases during progression of the immunoglobulin rearrangement process in the
      pre-B-cell ontogeny. This is probably due to decreased accessibility of the bcl-2
      locus by reduced transcription. We analysed the somatic mutation pattern of the
      productively rearranged IgH gene. Like other follicular lymphomas, somatic
      mutations were present in this gene and indicated positive selection, probably
      for an antigen. We found no evidence for ongoing induction of somatic mutations
      during lymphoma development. We conclude that bcl-2 gene deregulation, but not
      the precise moment at which this occurs during the pre-B-cell stage, influences
      the development of follicular NHL.

PMID- 8555067
TI  - Quantitative flow cytometry can distinguish between normal and leukaemic B-cell
      precursors.
AB  - The immunological detection of minimal residual disease in B-lineage acute
      lymphoblastic leukaemia (ALL) has been hampered by the fact that the leukaemic
      cells represent the malignant counterparts of normal haemopoietic precursors
      expressing terminal deoxynucleotidyl transferase (TdT), CD10 and CD19. We have
      used quantitative double-labelling flow cytometry with standard fluorescent beads
      to convert the mean fluorescence to the number of antigen molecules per cell. The
      number of TdT, CD10 and CD19 molecules per cell was determined in normal B-cell
      precursors from 22 healthy donors and eight regenerating marrows from patients
      with various malignancies and in 20 cases of B-lineage ALL. In normal bone marrow
      we characterized two different B-cell populations: TdT+/CD10+/CD19+ and TdT
      /CD10+/CD19+. We demonstrated a major difference in the level of expression of
      TdT, CD10 and CD19 between normal bone marrow and B-lineage ALL blasts. Normal
      TdT+ precursors have significantly higher number of TdT (> 100 x 10(3)) and lower
      number of CD10 (< 50 x 10(3)) and CD19 (< 10 x 10(3)) molecules per cell than B
      lineage ALL blasts (< 100, > 50, > 10 x 10(3) molecules per cell respectively);
      these differences were statistically highly significant. Furthermore,
      regenerating marrows had a significantly higher percentage of B-cell precursors
      than healthy donors. This increase was at the expense of the TdT-/CD10+/CD19+
      population which, in the context of B-lineage ALL, could be wrongly interpreted
      as evidence of relapse if TdT is not included in the analysis. Therefore the
      quantitative analysis of TdT combined with CD10 and CD19 may allow a clear
      distinction between normal precursors and minimal residual leukaemia in B-lineage
      ALL and avoid the pitfall of misinterpreting regenerating B-cells as evidence of
      relapse.

PMID- 8555068
TI  - High frequency of homozygous deletions of CDK4I gene in childhood acute
      lymphoblastic leukaemia.
AB  - To determine the incidence of homozygous deletions of the newly identified tumour
      suppressor gene, CDK4I, molecular genomic DNA analyses by PCR technique were
      performed on primary neoplastic cells from 22 childhood acute leukaemias obtained
      at presentation. The blast cells derived in all the analysed cases from bone
      marrow. We found that none of acute myeloblastic leukaemias (four cases) showed
      the CDK4I alteration, whereas 6/13 (46%) common acute lymphoblastic leukaemias
      (ALLs) displayed homozygous deletions. Moreover, and even more important, all the
      blasts purified from ALLs derived from early lymphoid precursors (three early-T
      ALLs and two pre-B ALLs) showed the absence of CDK4I gene. When the entire coding
      sequence of the CDK4I gene from samples without homozygous deletions was analysed
      by the single-strand conformational polymorphism method, no point mutations were
      identified. These results demonstrate that CDK4I gene deletions are very frequent
      and probably early events in childhood acute leukaemias of lymphoid origin and
      especially in early-T and pre-B ALLs. Moreover, the molecular mechanism of the
      loss of function of the gene is correlated, at least in childhood ALLs, almost
      exclusively to deletions and not to point mutations.

PMID- 8555069
TI  - Decreased potency of MDR-modulators under serum conditions determined by a
      functional assay.
AB  - A variety of agents are capable of overcoming P-glycoprotein-mediated multidrug
      resistance (MDR) in vitro. However, the clinical potential of these compounds is
      often limited due to high plasma protein binding. We compared the efficacy of
      several MDR-reversing compounds in serum-free culture medium and under serum
      conditions by means of a functional assay. Using flow cytometry the efflux of the
      fluorescent dye rhodamine 123 (Rh123) was measured from normal peripheral blood
      CD8+ T-lymphocytes which express low levels of P-glycoprotein. Inhibition of
      Rh123 efflux by R-verapamil, dexnigludipine-HCl, cyclosporin A, SDZ PSC833 and
      the protein kinase C (PKC) inhibitor CGP 41251 was determined in serum-free
      medium and in serum at concentrations from 0.1 to 50 mumol/l. With the exception
      of SDZ PSC833 all MDR modulators showed an insufficient or suboptimal modulation
      of P-glycoprotein under serum conditions at concentrations achievable in vivo.
      The highest potency under serum conditions demonstrated SDZ PSC833: even at a
      concentration of 0.5 mumol/l a sufficient inhibitory effect was observed.
      Subsequently this approach was applied to patients suffering from B-cell chronic
      lymphocytic leukaemia (B-CLL; n = 3) and acute myeloid leukaemia (AML; n = 2)
      which were positive in the Rh123 efflux assay. As for normal CD8+ T-lymphocytes,
      much higher drug concentrations were required under serum conditions to
      effectively inhibit Rh123 efflux from the leukaemic cells. Thus the
      interpretation of results of clinical 'modulator' trials should consider the
      decreased bioavailability of MDR-reversing agents.

PMID- 8555070
TI  - The value of magnetic resonance imaging in screening myeloma lesions of the
      lumbar spine.
AB  - Screening of the skeleton by plain radiography was compared to magnetic resonance
      imaging (MRI) of the lumbar spine in 41 patients with multiple myeloma. In the
      lumbar spine, myeloma lesions were detected in 15 patients with radiography and
      in 28 patients with MRI. Radiography of the lumbar spine was not positive in any
      of the 13 cases with negative MRI, but in two of them radiography was positive
      elsewhere in the skeleton. We suggest that plain radiography is the most suitable
      method for screening all bone areas in multiple myeloma, but MRI of the lumbar
      spine is needed to study patients with normal radiographs.

PMID- 8555071
TI  - c-kit point mutation of extracellular domain in patients with myeloproliferative
      disorders.
AB  - c-kit is a tyrosine kinase receptor whose ligand is stem cell factor (SCF). Gene
      alteration of the c-kit extracellular domain was analysed by polymerase chain
      reaction-single strand conformation polymorphism (PCR-SSCP) in 25 patients with
      myeloproliferative disorders (MPD). In the N-terminal part of the domain,
      mobility shifts indicating sequence alteration were detected in three of the
      patients, two primary myelofibrosis (PMF) and one chronic myelogenous leukaemia
      (CML). The subsequent sequencing revealed the same point mutations at codon 52
      causing amino acid substitution (Asp-->Asn). To our knowledge this is the first
      report with a c-kit point mutation found in human fresh tumour cells.

PMID- 8555072
TI  - High incidence of deletions but infrequent inactivation of the retinoblastoma
      gene in human myeloma cells.
AB  - We have studied the retinoblastoma (RB-1) susceptibility gene status and pRB
      expression in 22 human myeloma cell lines (HMCL) and in 10 patients with advanced
      multiple myeloma (MM). Deletions of the RB-1 gene were observed in 81% (17/21) of
      the informative HMCL, regardless of their paracrine or autocrine interleukin-6
      (IL-6) status. Among the deleted HMCL, only one (U266) had a biallelic deletion
      and lacked pRB expression. Monoallelic deletions had no consequence on the RB-1
      gene activation and pRB expression. One patient of 10 presented the same
      biallclic deletion as U266 and six of 10 had monoallelic deletions. We conclude
      that monoallelic deletions of the RB-1 gene are frequent in HMCL and MM patients
      but have no consequence on gene activation and pRB expression.

PMID- 8555073
TI  - 2-Chloro-deoxyadenosine therapy for giant lymph node hyperplasia.
AB  - Giant lymph node hyperplasia (GLNH) or Castleman disease is a heterogenous group
      of atypical lymphoproliferative disorders. Two main histologic variants, the
      hyaline vascular variant and the plasma cell variant, have been recognized.
      Although localized GLNH can often be managed successfully with surgery, optimal
      therapy for multifocal disease has yet to be identified. We report two cases of
      GLNH treated with 2-chloro-deoxyadenosine (2-CDA), a synthetic purine analogue. 2
      CDA was utilized based on its relative lymphocytic toxicity and the putative
      pathophysiologic process in GLNH being either hamartomatous overgrowth (hyaline
      vascular variant) or immune dysfunction and lymphoproliferation (plasma cell
      variant). One patient with unresectable localized hyaline-vascular GLNH has had a
      9-month continuous complete remission following two courses of 2-CDA therapy
      followed by radiation therapy. The second patient with disseminated plasma cell
      type had a partial response to two cycles of 2-CDA therapy; however, further
      cycles were not given due to development of possible early neurotoxicity.
      Although the optimal management of non-resectable GLNH is yet to be determined, 2
      CDA appears to be a viable therapeutic option for patients with this disease
      process.

PMID- 8555074
TI  - Decreased production of interferon gamma by anti-CD3 monoclonal antibody and
      interleukin-2-stimulated peripheral blood mononuclear cells in Hodgkin's disease.
AB  - We have examined the production of interferon (IFN) gamma by peripheral blood
      mononuclear cells (PBMC) in 22 patients with Hodgkin's disease (HD) in active
      phase of the disease, 12 patients in clinical remission and 16 healthy subjects.
      The level of IFN gamma in supernatants of PBMC stimulated for 72 h with anti-CD3
      monoclonal antibody (mAb), measured by sandwich enzyme immunoassay (ELISA) was
      50.4 +/- 2.3 U/ml in active phase; 137.0 +/- 7.4 U/ml in clinical remission
      patients; and 520.0 +/- 10.0 U/ml in the controls; the difference between the
      groups was statistically significant. Co-stimulation with interleukin-2 (rIL-2)
      markedly amplified production of IFN gamma. The mean levels were 220.8 +/- 7.0
      U/ml, 590.7 +/- 3.6 U/ml and 2111.1 +/- 17.3 U/ml in active phase HD, clinical
      remission and controls, respectively, the difference between groups was
      statistically significant. The patients showed the same kinetic pattern as
      healthy individuals. Our results indicate that patients with HD have severely
      impaired TCR/CD3 activation pathway resulting in significantly depressed IFN
      gamma response to anti-CD3 mAb and anti-CD3 + rIL-2 in vitro stimulation and
      provide support for the possible clinical use of IFN gamma as an
      immunopotentiating agent in patients with HD.

PMID- 8555075
TI  - Quantitation of human cytomegalovirus DNA in bone marrow transplant recipients.
AB  - HCMV DNA was retrospectively quantitated in the early post-transplant period in
      36 paediatric bone marrow transplant (BMT) recipients prospectively monitored for
      human cytomegalovirus (HCMV) infection on the basis of antigenaemia and viraemia
      assays. Viral DNA was quantitated in peripheral blood leucocytes (PBL) by PCR
      using an internal control of amplification and a series of external standards.
      Densitometric analysis of hybridization results obtained on PCR products enabled
      construction of a standard curve from which DNA amounts of clinical samples,
      expressed in terms of genome equivalents (GE), were interpolated. Of the 36 BMT
      recipients, three had clinically symptomatic HCMV infection with mean peak levels
      of viral DNA > 5000 GE (antigenaemia and viraemia mean peak levels were 873 and
      35, respectively), whereas 19 with HCMV reactivation were asymptomatic (five of
      them had abortive HCMV infection) showing mean peak DNA levels of 131 GE (and of
      6.8 and 1.3 for antigenaemia and viraemia, respectively) (P < or = 0.01). Single
      or multiple courses of pre-emptive therapy with ganciclovir or foscarnet were
      given to 14/19 asymptomatic children in whom antigenaemia levels were > 2 or
      lower yet persisting. Overall, in the 14 asymptomatic treated patients the mean
      antigenaemia level was 9.3 (range 1-22), and the mean DNA level was 184.6 (range
      20-710) GE. Antiviral drugs were also administered to the three symptomatic
      patients who, due to late diagnosis of HCMV infection, escaped preemptive
      therapy. Antiviral treatment caused marked decrease or disappearance of viral
      DNA, antigenaemia and viraemia in both symptomatic and asymptomatic patients. In
      conclusion, our study suggests that: (i) starting therapy in the presence of a
      mean antigenaemia level of 9.3 (range 1-22) corresponding to a mean DNA level of
      184.6 (range 20-710) GE avoided occurrence of any major HCMV-related clinical
      complication; (ii) clinical symptoms were associated with antigenaemia levels >
      100 and DNA levels > 1000 GE; (iii) the effect of antiviral treatment could be
      more carefully monitored by quantitation of viral DNA.

PMID- 8555076
TI  - Experience with liposomal Amphotericin-B in 60 patients undergoing high-dose
      therapy and bone marrow or peripheral blood stem cell transplantation.
AB  - 60 patients undergoing bone marrow or stem cell transplantation were treated with
      liposomal Amphotericin-B for documented or suspected mycosis. 34 patients had a
      prior course of conventional Amphotericin-B with the following adverse effects:
      increasing creatinine above 1.4 mg/dl (n = 17), increasing creatinine below 1.5
      mg/dl (n = 9), no response (n = 6), and clinical side-effects (n = 4). Liposomal
      Amphotericin-B failed in 6/7 patients with culture-proven mycosis who died from
      infection with Aspergillus (n = 2) and Candida (n = 4), respectively. One patient
      with Candida lambica sepsis was cured. No patient with clinically or
      serologically suspected or diagnosed infection died from mycosis. Liposomal
      Amphotericin-B was well tolerated in 57 patients, even after side-effects of the
      conventional formulation. Adverse effects occurred in three cases, requiring the
      withdrawal of the drug in one patient. Due to toxic side-effects of the high-dose
      therapy and transplant-related complications, it was difficult to evaluate the
      influence of liposomal Amphotericin-B on laboratory parameters. Eight patients
      showed a decrease of creatinine levels, which had increased above normal values
      under preceding therapy with conventional Amphotericin-B. Liposomal Amphotericin
      B is well tolerated in patients undergoing high-dose therapy and bone marrow
      transplantation. The efficacy of liposomal Amphotericin-B needs to be
      investigated in randomized studies in comparison with conventional Amphotericin
      B.

PMID- 8555077
TI  - Autoimmune-prone (NZW x BXSB)F1 (W/BF1) mice escape severe thrombocytopenia after
      treatment with deoxyspergualin, an immunosuppressant.
AB  - Male (NZW x BXSB)F1 mice spontaneously develop a disease which closely resembles
      human systemic autoimmune disease, involving idiopathic thrombocytopenic purpura
      and glomerulonephritis. We investigated whether autoimmune thrombocytopenia in
      the mice responded to deoxyspergualin, as immunosuppressant. Deoxyspergualin
      completely prevented the development of thrombocytopenia and suppressed the
      increase in circulating autoantibodies against platelets. This agent also
      ameliorated lupus nephritis. These findings suggest that deoxyspergualin may be
      effective in the prevention of idiopathic thrombocytopenic purpura.

PMID- 8555078
TI  - Activated platelets in paroxysmal nocturnal haemoglobinuria.
AB  - One of the major causes of morbidity and mortality in paroxysmal nocturnal
      haemoglobinuria (PNH) is venous thrombosis. We have studied fibrinolysis,
      coagulation and platelets in 11 patients with PNH in an attempt to identify the
      possible mechanism(s) of thrombosis in PNH. In this study we did not identify any
      fibrinolytic defects, evidence of coagulation activation, nor reduction in
      coagulation inhibitors. In contrast, in this cohort of 11 PNH patients we have
      identified varying degrees of platelet activation as defined by the surface
      expression of activation-dependent proteins and the binding of adhesive proteins
      to the platelet surface. The thrombotic events in PNH usually occur in the venous
      system. Our studies and previous experimental studies suggest that anti-platelet
      therapy may be efficacious in reducing the incidence and severity of venous
      thrombosis in PNH.

PMID- 8555079
TI  - Persistent hepatitis C virus RNA replication in haemophiliacs: role of co
      infection with human immunodeficiency virus.
AB  - In order to evaluate the evolution of transfusional hepatitis C in haemophiliacs,
      we performed a retrospective study of ALT levels and HCV viraemia with a RNA PCR
      assay in 57 patients. We found that the vast majority of HCV-infected patients
      remained viraemic (43/57 = 75%) and higher ALT levels correlated with HCV
      viraemia. Although indicators of the transfusional viral load (age, severity of
      haemophilia) and HBV co-infection did not correlate with HCV RNA replication, HIV
      seropositivity was strongly associated with persistence of HCV viraemia (23/25 =
      92% in HIV-positive versus 20/32 = 62% in HIV-negative patients), without any
      correlation with CD4 counts. Genotyping of HCV in the 43 viraemic patients shows
      more frequent genotype 1 in the HIV-seropositive group (14/23) than in the
      seronegative group (6/20). Our data emphasize that besides the role of the
      immunodeficiency status, the genotypes of HCV might be involved in the
      differences observed in terms of HCV RNA replication between the HIV-seropositive
      and seronegative haemophiliacs.

PMID- 8555080
TI  - Hepatitis C virus genotypes and severity of chronic liver disease in
      haemophiliacs.
AB  - We studied the activity and stage of chronic liver disease in 45 HCV
      seropositive/HIV-seronegative patients with severe haemophilia followed for at
      least 10 years. HCV-RNA was detected in serum in 36 patients (80%) Viraemic cases
      were further analysed for HCV genotypes: 10 (28%) were infected by type 1a, 10
      (28%) by type 1b, seven (19%) by type 2, four (11%) by type 3, four (11%) had
      mixed infections (one by 1a + 1b, one by 1a + 2, one by type 2 + 3, and one by 1a
      + 2 + 3). ALT levels were within the normal range in 55% of the HCV-RNA negative
      patients but in only 11% of the viraemic cases. Results show a trend for higher
      levels of ALT in HCV-RNA-positive patients compared with those without viraemia
      (98 +/- 56 v 60 +/- 61), and particularly with patients with type 3 HCV infection
      (148 +/- 44). We suggest that a slow progression of chronic liver disease occurs
      in haemophilic HCV-positive/HIV-negative patients and conclude that presence of
      HCV-RNA in serum correlates well with cytolitic damage but, in the time-scale of
      our follow-up period, commonly used clinical-laboratory parameters cannot predict
      the chronic evolution of liver infection or identify differences in disease
      progression in relation to specific HCV subtypes.

PMID- 8555081
TI  - Common inhibitory effects of human anti-C2 domain inhibitor alloantibodies on
      factor VIII binding to von Willebrand factor.
AB  - Factor VIII (FVIII) inhibitor alloantibodies obtained from seven severe
      haemophilia A patients were examined for their binding regions and their effects
      on FVIII binding to von Willebrand factor (vWF). Immunoblotting analysis with a
      panel of recombinant fragments demonstrated that the binding regions of
      antibodies in cases 1-5 were contained in the C2 domain of the light chain.
      Antibodies from cases 1 and 2, which recognized an epitope within residues 2248
      2312, completely inhibited FVIII/vWF binding in an ELISA (IC50: 5.0 and 9.0
      micrograms/ml, respectively). Antibodies from case 3 recognizing 2170-2312 and
      case 5 recognizing 2170-2327 also inhibited FVIII/vWF binding (IC50: 110 and 400
      micrograms/ml, respectively). Case 4 antibodies recognizing 2218-2307 showed
      barely detectable inhibition and cases 6 and 7 antibodies recognizing the 44 kD
      heavy chain, did not inhibit. Our results demonstrate that all anti-C2
      alloantibodies with epitopes that extend to the residue 2312 inhibit vWF binding
      and that an overlap of the inhibitor epitope with residues 2308-2312 is critical
      for maximal inhibition of vWF binding. Prevention of FVIII/vWF binding appears to
      be a common property of anti-C2 domain inhibitor alloantibodies.

PMID- 8555082
TI  - Genetic diagnosis of haemophilia A of Chinese origin.
AB  - Genetic diagnosis of haemophilia A has been studied in two aspects. One is to
      directly identify the mutations in the factor VIII genes of the affected
      probands, and the other is to examine the usefulness of several intragenic factor
      VIII markers for gene tracking. Direct mutational analysis by PCR-SSCP
      (polymerase chain reaction--single-strand conformation polymorphism) has been
      accomplished previously in 87 haemophilia A patients, accounting for nearly 10%
      of cases in Taiwan. Of the 87 cases, 46% were with point mutations, short
      deletions or insertions, and most of the remaining were with gene inversion
      readily identified by Southern blotting. Further examination of 112 patients has
      estimated a 33% incidence for gene inversion in all the patients with haemophilia
      A, or 37% in severe cases. Since the direct mutational detection described above
      cannot be used in all Chinese families with haemophilia A, genetic markers were
      also investigated. The two CA repeat markers located at intron 13 (CA-13) and
      intron 22 (CA-22), respectively, were amplified and analysed simultaneously.
      Seven different alleles with 18-24 CAs have been identified for CA-13. Alleles of
      20 and 21 CAs are the most common and their population frequency was 0.68 and
      0.24, respectively. The CA-22 marker contained a repetition of (GT)n(AG)n as was
      identified in the white European but not in the Canadian population. Alleles with
      25 and 26 GT/AGs account for 18% and 75% of this group of samples, respectively.
      The expected rate of heterozygosity for either CA markers was 68%, although a
      value of 57% was observed by haplotype analysis, indicating an association of the
      two repeat markers. Nevertheless, the study of 62 females showed that with the
      combined use of CA-13 and CA-22 with BclI, approximately 71% would be informative
      for these markers. This number may increase to 81% if XbaI polymorphism is added.
      We propose that a better genetic diagnosis procedure for Chinese individuals
      would be first to look for the inversion mutation, secondly for one of the
      intragenic markers, and then at the PCR-SSCP analysis.

PMID- 8555083
TI  - Molecular basis of inherited factor XIII deficiency: identification of multiple
      mutations provides insights into protein function.
AB  - Factor XIII (FXIII) is a zymogen essential for normal haemostasis. In inherited
      FXIII deficiency the majority of cases show absence of the FXIIIa subunit.
      Molecular analysis of PCR-amplified FXIIIa subunit exonic regions, and of RT-PCR
      amplified cDNA from six patients with FXIIIa subunit deficiency, from five
      unrelated families, has revealed 10 sequence changes: three mutations resulting
      in abnormal splicing of pre-mRNA, one nonsense mutation, one deletion/insertion
      change, three point mutations producing Val34Leu, Asn60Lys and Arg408Gln changes,
      and two silent mutations. In three families the patients are homozygous for a
      specific deficiency causing mutation, and patients from the remaining two
      families are compound heterozygotes. Understanding the molecular pathology of the
      disorder provides insights into the structure-function relationships of the
      various domains within the FXIII protein. From a clinical point of view, it
      enables direct diagnosis at the DNA level and may aid the development of FXIII
      analogues to promote wound healing.

PMID- 8555084
TI  - Heparin-induced thrombocytopenia: cross-reactivity between standard heparin, low
      molecular weight heparin, dalteparin (Fragmin) and heparinoid, danaparoid
      (Orgaran).
AB  - The incidence of cross-reactivity between unfractionated heparin and LMWH,
      fragmin, in patients with HIT is significantly lower (6/15, 40%) than hitherto
      reported in the literature. 7/9 patients with a negative cross-reactivity test
      were treated with dalteparin sodium (Fragmin) without any untoward events.

PMID- 8555085
TI  - Severe arterial thrombosis in a congenitally factor VII deficient patient.
AB  - We report a patient with congenital factor VII deficiency who developed severe
      arterial thrombosis. A 63-year-old-woman presented low factor VII clotting
      activity, amidolytic activity and antigen level < 4%. Activated factor VII
      plasmatic level was < 0.03 ng/ml compared to 4 ng/ml for the control value. She
      developed severe aorto-iliac thrombosis. 7 d before the thrombotic event, factor
      VII replacement therapy had been infused. Successful low molecular weight heparin
      therapy led to total disappearance of the aorto-iliac thrombus without bleeding
      complications. This suggests that factor VII infusion might have a thrombogenic
      effect in vivo and might be responsible for thrombosis.

PMID- 8555086
TI  - The prenatal identification of fetal compatibility in neonatal alloimmune
      thrombocytopenia using amniotic fluid and variable number of tandem repeat (VNTR)
      analysis.
AB  - Most severe episodes of neonatal alloimmune thrombocytopenic purpura (NATP) are
      caused by antiplatelet alloantibodies against the HPA-1a (PlA1) antigen. However,
      half of subsequent fetuses produced from a HPA-1a/b father (genotypic frequency
      28%) will result in a child who is not affected. Some investigators manage NATP
      by confirming the fetal platelet phenotype using percutaneous umbilical cord
      sampling, a procedure that carries a low but real risk of fetal morbidity and
      mortality. More recently, physicians determine the fetal platelet antigen
      genotype using DNA derived from amniotic fluid or chorionic villus samples. All
      therapy is withdrawn for a fetus who genotypes as HPA-1b/b. However, since the
      fetus is the same genotype as the mother, there can be uncertainty about the
      origin of the genetic material and thus the validity of the fetal genotype. The
      inappropriate withdrawal of therapy for a erroneously genotyped fetus could be
      fatal, and consequently many physicians advocate fetal HPA-1 phenotyping with
      confirmation using percutaneous umbilical blood sampling. In this report we
      describe the management of two pregnancies with previously affected infants due
      to anti-HPA-1a alloantibodies. Both husbands were HPA-1a/b. For the current
      pregnancies, amniotic fluid was collected at 20 or 29 weeks of gestation, and the
      platelet genotype indicated that the fetuses were HPA-1b/b. The fetal origin of
      the amniotic fluid derived DNA was confirmed by the forensic technique of DNA
      profiling using variable number of tandem repeat (VNTR) analysis. All therapy was
      withdrawn, percutaneous umbilical blood sampling was not performed, and both
      women vaginally delivered healthy non-thrombocytopenic infants. The application
      of platelet alloantigen genotyping using DNA from amniotic fluid cells identified
      the HPA-1b/b fetus, and VNTR analysis confirmed that the tissue was fetal
      derived, thus avoiding the necessity for percutaneous umbilical blood sampling.
      The use of this approach in patients at risk will avoid additional investigation
      and treatment in approximately one-seventh of all NATP pregnancies involving the
      HPA-1a antigen.

PMID- 8555087
TI  - Bilateral linkage between a new deletion polymorphism in intron 21 of the GP IIb
      gene and the HPA-3b (Bakb) determinant.
AB  - Glycoproteins (GP) IIb (alpha IIb) and GP IIIa (beta 3) form heterodimeric
      complexes (GP IIb-IIIa) at the platelet surface and mediate platelet aggregation
      by binding fibrinogen after platelet activation. The structures and DNA sequences
      of the GP IIb and GP IIIa genes are known. Punctual mutations resulting in
      alloantigen systems (HPA) have been described on both genes, as have a series of
      genetic defects giving rise to Glanzmann's thrombasthenia (GT). We now report a
      nine base pair deletion located in intron 21 of the GP IIb gene. This was found
      both in unrelated GT patients and in normal individuals. Subsequent studies
      showed that the deletion polymorphism and the mutation responsible for the
      platelet alloantigen. HPA-3b, were linked together. The deletion was always
      present when the gene carried the HPA-3b genotype, but was never observed in
      association with the HPA-3a polymorphism. Analysis of 60 independent alleles from
      30 unrelated caucasian individuals revealed no exceptions to this linkage. It is
      the first time that two genetic markers have been reported to be linked to each
      other on the GP IIb gene.

PMID- 8555088
TI  - The Pasteur effect in human platelets: implications for storage and metabolic
      control.
AB  - The Pasteur effect and the associated acidosis have long been considered a major
      cause of platelet death during storage. We have investigated this phenomenon
      using a defined platelet preparation and a system whereby the oxidative and
      glycolytic contributions to total ATP production can be measured over a range of
      oxygen concentrations from saturating (pO2 = 158 mmHg) to anoxic (pO2 = 0 mmHg).
      Platelets do not show a Pasteur effect until the pO2 decreases to < 2.0 mmHg,
      whereupon lactate production increases 1.5-fold. The Pasteur effect is therefore
      not a likely cause of platelet death during storage where pO2 in a storage bag
      typically drops to no less than 50 mmHg. The data also have implications for the
      role of oxygen diffusion in oxidative metabolism, and for the compensatory nature
      of the Pasteur effect. As platelets are relatively small cells, and the onset of
      the Pasteur effect occurs at a relatively low oxygen concentration, diffusion may
      limit the rate of oxygen consumption in most other (larger) cells. The Pasteur
      effect is only fully compensative if the P/O2 ratio used for the calculations is
      lower than the conventional one. Since recent research strongly suggests that the
      conventional P/O2 ratio is too high, examples of fully compensative Pasteur
      effects may be more common than the literature suggests.

PMID- 8555089
TI  - Antigen-independent reactivation of anti-E, years after allogeneic bone marrow
      transplantation: a case report.
AB  - Nine years after allogenic bone marrow transplantation a strong anti-E was
      observed in a patient transplanted with bone marrow from his HLA-identical
      brother. This IgG anti-E, with a titre of 4000, was detected together with
      autoantibodies to red blood cells and platelets and was not induced by
      transfusion with E+ cells. The hypothesis is proposed that the anti-E represents
      either antigen-independent desuppression of the donor immune system sensitized at
      the time of bone marrow transplantation by E antigens in the recipient, or
      antigen-independent memory B-cell activation by Epstein-Barr virus infection.

PMID- 8555090
TI  - Single amino acid mutation of Fc gamma receptor is associated with the
      development of heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is mediated by a heparin-dependent
      antibody/platelet factor 4/heparin complex binding to platelets via the Fc gamma
      receptor (type IIA). A single base polymorphism at position 131 of Fc gamma RIIA
      changes the native arginine to histidine. In the presence of murine monoclonal
      IgG1 the former phenotype (Fc gamma RIIAArg131) is functionally characterized by
      strong platelet aggregation (high responder) and the latter (Fc gamma RIIAHis131)
      by poor aggregation (low responder). In the presence of human IgG2 the opposite
      response is observed. It has recently been shown that the heparin-dependent
      antibody is predominantly of this subclass. We hypothesize that a relationship
      exists between Fc gamma RIIAHis131 and the development of HIT. We studied 24
      normal individuals and 20 HIT patients using VM58, a murine monoclonal IgG1, to
      characterize the phenotype by platelet aggregrometry, and PCR products, amplified
      with primers bordering the Fc gamma RIIA polymorphism and hybridized with
      oligonucleotide probes specific for the single base mutation, to determine the
      genotype. The distribution of phenotypes and genotypes in the two populations
      differed, with a greater prevalence of the Fc gamma RIIAHis131 allele in the HIT
      patient population. Homozygous Fc gamma RIIAArg131 individuals were absent from
      this group. We conclude that the presence of the Fc gamma RIIAHis131 allele is
      associated with a predisposition to HIT.

PMID- 8555091
TI  - Accessory cells do not contribute to G-CSF or IL-6 production nor to rapid
      haematological recovery following peripheral blood stem cell transplantation.
AB  - Haemopoietic recovery is more rapid after peripheral blood stem cell (PBSC)
      transplantation than after autologous bone marrow transplantation, and the aim of
      this study was to assess the role of the large number of lymphocytes and
      monocytes (accessory cells) in a PBSC leukapheresis product in this rapid
      regeneration. Haematological recovery was therefore assessed in 10 PBSC
      recipients with lymphoma or myeloma in whom monocytes and T cells were depleted
      by a median of 2.3 and 3.3 logs by CD34+ cell selection using the CEPRATE SC stem
      cell concentration system and compared with recovery in 59 recipients who
      received whole PBSC. After allowing for the number of progenitor cells reinfused,
      there was no significant delay in engraftment induced by accessory cell
      depletion. Plasma levels of granulocyte-colony stimulating factor (G-CSF),
      granulocyte/monocyte-colony stimulating factor (GM-CSF), interleukin-6 (IL-6),
      stem cell factor (SCF) and macrophage-inhibition factor-alpha (MIP-1-alpha)
      during the transplant procedure were similar whether or not accessory cells were
      given. The G-CSF and IL-6 levels rose between days 5 and 14 post transplantation
      to approximately 1 ng/ml and 50 pg/ml respectively. This study indicates that
      accessory cells reinfused with PBSC collections are not responsible for the
      subsequent cytokine profile or rapid haematological recovery.

PMID- 8555092
TI  - Treatment with retinoids and haemopoietic growth factors in myelodysplastic
      syndromes.

PMID- 8555093
TI  - Haemophagocytic lymphohistiocytosis: an inherited primary form and a reactive
      secondary form.

PMID- 8555094
TI  - TH1-type immune response in lymphocyte-predominance Hodgkin's disease.

PMID- 8555095
TI  - Primary tumors of the spine in children--natural history and management. 1990.

PMID- 8555096
TI  - Prognosis of extradural haematomas in children.
AB  - 102 children treated surgically for intracranial extradural haematoma from 1982
      to 1991 were evaluated retrospectively and their prognosis was compared with 387
      adults treated during the same period. Children had a better prognosis than
      adults even with a low Glasgow Coma Scale (GSC) score at surgery. Children had a
      higher incidence of frontal and posterior fossa haematomas. The GCS score and the
      associated parenchymal injuries had a strong correlation with the outcome both in
      adult and children, whereas the site of haematoma had no correlation with the
      final outcome.

PMID- 8555097
TI  - Results and complications of intracranial pressure monitoring in 303 children.
AB  - 303 consecutive children who had insertion of an intracranial pressure (ICP)
      monitor for various reasons were reviewed to determine clinical value and
      complications rate of ICP monitoring in this age group. 286 patients had a Camino
      fiberoptic monitor. Of the remaining cases, 9 had a ventricular catheter, 7 had
      an extradural Gaeltec monitor, and 1 had a subdural feeding tube. The reasons for
      monitoring the ICP were: trauma in 132 children, postoperative monitoring after
      tumor surgery in 91, head injury due to child abuse in 30, severe medical
      conditions such as meningitis, encephalitis, and near-drowning in 30,
      intracranial hemorrhage in 15, and hydrocephalus in 5 children. The median age at
      insertion was 6 years (range from 1 month to 17 years), and the median Glasgow
      coma score before insertion was 7. Median duration of monitoring was 3 days, and
      35 children (10%) had surgical procedures performed for raised ICP detected by
      monitoring. 238 (78%) had nonsurgical measures to control raised ICP. 6 (15%) of
      40 children with an initial ICP > 50 mm Hg made a good recovery, but there were
      no survivors among 37 children who had an ICP consistently > 60 mm Hg and only 1
      disabled survivor among 42 children with an ICP consistently > 50 mm Hg. The
      outcome in all 303 children correlated with averaged readings of ICP over 24 h
      and initial Glasgow coma score, but did not correlate with initial ICP
      measurements. Complications of monitoring were few and consisted of infection in
      1 (0.3%) child, intracranial hemorrhage in 1 (0.3%) who had low platelet counts,
      displacement of monitor in 3 (1%), and malfunction of monitor in 8 (2.6%)
      children. We conclude that ICP monitoring in the pediatric age group
      substantially influences our clinical management of unconscious children and is
      safe.

PMID- 8555098
TI  - Changes in cognitive performance in children with spastic diplegic cerebral palsy
      following selective dorsal rhizotomy.
AB  - Children with cerebral palsy who receive selective dorsal rhizotomy (SDR) for
      treatment of spasticity may show suprasegmental changes in upper limb function
      and control of speech musculature. Anecdotal reports suggest that supra-segmental
      effects may extend to cognitive functions such as attention and language. This
      study examined the performance of 16 children with spastic diplegic cerebral
      palsy on tests of visual attention and other cognitive functions 1 day prior to
      and 6 months following SDR. Children undergoing SDR were compared with 9 children
      with spastic diplegia, matched for severity of cerebral palsy and amount of
      therapy, who did not receive SDR, and 24 age- and sex-matched normal children
      tested at initial and 6-month follow-up sessions. Children with cerebral palsy
      treated with SDR showed disproportionately greater improvement in specific
      attentional and cognitive operations than either of the other groups. These
      results document cognitive changes following SDR which heretofore were reportedly
      anecdotally. This improvement may be due to improved mood, reduced physical
      discomfort, increased therapeutic intervention, or possible cortical effects of
      SDR.

PMID- 8555099
TI  - Foot contact pattern following selective dorsal rhizotomy.
AB  - Fourteen ambulatory patients with spastic cerebral palsy were evaluated prior to
      and 6 months following selective dorsal rhizotomy. An instrumented gait analysis
      identified significant improvements in foot contact patterns, velocity and stride
      length. The high incidence of postoperative valgus, excessive dorsiflexion and
      persistent knee flexion during gait was attributed to significant weakness and
      hypotonicity in the plantar flexors, as well as residual hamstring spasticity (p
      < 0.05). Sectioning of fewer S-1 rootlets may preserve plantar flexion strength
      and enhance stance stability by preventing postoperative increases in
      dorsiflexion and knee flexion. Orthotic prescription for ankle instability should
      be a routine postoperative consideration.

PMID- 8555100
TI  - Effects of continuous intrathecal baclofen infusion and selective posterior
      rhizotomy on upper extremity spasticity.
AB  - This study was performed to compare the effects of continuous intrathecal
      baclofen infusion (CIBI) and selective posterior rhizotomy (SPR) on upper
      extremity (UE) spasticity and range of motion in children with cerebral palsy.
      Spasticity was assessed with the Ashworth scale of muscle tone and range of
      motion was evaluated. Thirty-eight patients who had been treated with CIBI for at
      least 6 months were paired, according to pretreatment UE muscle tone and
      functional status, with 38 patients who had undergone SPR. The CIBI dosage had
      been titrated to reduce over lower extremity spasticity and improve lower
      extremity function, rather than to improve UE tone. The pretreatment muscle tone
      in the two groups was virtually identical. The UE tone of children treated with
      CIBI decreased from 2.07 prior to treatment to 1.66 after 1 year (p < 0.01). The
      tone of children treated with SPR decreased from 2.03 to 1.70 after 1 year (p =
      0.005). In that group, the likelihood of a clinically significant reduction in
      muscle tone (one point or greater) was greater in children with a higher
      pretreatment UE muscle tone. There was no correlation between the percentage of
      posterior lumbar roots divided in SPR and the subsequent reduction in UE tone.
      There were no significant changes in the range of motion in any UE joint, at
      either 6 or 12 months, after either CIBI or SPR. We conclude that both CIBI and
      SPR significantly reduce UE spasticity, in addition to the previously documented
      reduction in lower extremity spasticity.

PMID- 8555101
TI  - Relationship between cerebellar appearance and function in children with Dandy
      Walker syndrome.
AB  - In children with Dandy-Walker syndrome (DWS), the relationship between cerebellar
      appearance on imaging and either cerebellar function or intellect is unknown. To
      evaluate those relationships, we retrospectively studied 20 patients with DWS
      treated in our institution between 1978 and 1994. The patients were treated with
      ventriculoperitoneal, cystoperitoneal, or ventriculocystoperitoneal shunts.
      Intellectual and cerebellar function were determined from neurological and
      developmental testing. Cerebellar development was evaluated by measuring
      cerebellar and posterior fossa volumes from computed tomography images; the ratio
      of cerebellar size to posterior fossa size was considered to reflect cerebellar
      development. The cerebellar function was normal in 50% and the intellectual
      function in 45% of the patients. There was no correlation between cerebellar size
      and intellectual development or cerebellar function. There was also no
      correlation between the type of shunt and the subsequent cerebellar size. We
      conclude that there is no relationship between the cerebellar development evident
      on computed tomography scans and the cerebellar or the intellectual function of
      children with DWS. We, therefore, infer that treatment of Dandy-Walker cysts with
      posterior fossa shunts is unlikely to enhance the cerebellar function.

PMID- 8555102
TI  - Masson's vegetant haemangio-endothelioma.
AB  - We present a 14-year-old patient who had a scalp mass that enlarged on dependent
      positioning. This mass was located in the surgical bed of a previously excised
      scalp lesion. Valsalva manoeuvre assisted computerized tomography demonstrated
      this lesion to enhance with contrast and to vary in size. At surgery, a bluish
      firm mass, located in the galea of the left frontal region, was resected. Total
      removal resulted in no recurrence at 18 months. Pathological examination revealed
      a vascular tumour that was first described by Pierre Masson. This is
      characterized by intravascular vegetations composed of cells of endothelial
      origin. The exact pathogenesis of these lesions is unknown, but the prognosis
      based on the review of the literature is expected to be good.

PMID- 8555103
TI  - Atypical cerebral aneurysm in a young child.
AB  - Autopsy findings are described of an atypical aneurysm of a large cerebral artery
      in a young child. The lesion is believed to have been an infective (mycotic)
      aneurysm. Antibiotics were administered at the time of the first leakage which
      had been thought to be due to a sinus infection. The sac wall exhibited a
      subacute pleomorphic inflammatory cell response indicative of a resolving
      infective aneurysm, and appearance that is likely to be encountered more often in
      the future.

PMID- 8555104
TI  - Conservation of structure and expression of the trithorax gene between Drosophila
      virilis and Drosophila melanogaster.
AB  - The Drosophila melanogaster trithorax gene encodes several large RNAs which are
      expressed in complex patterns in the embryo. The D. virilis trithorax gene was
      isolated and sequenced. It produces a similar to D. melanogaster set of
      transcripts, and it encodes a protein that shows sequence similarity in several
      domains which are also conserved in human homologue, ALL-1/HRX. Previous
      experiments have suggested that a distinct expression domain of trithorax in the
      posterior region of the embryo is required to maintain expression of the BX-C
      genes (Sedkov et al., 1994, Development 120, 1907-1917). At cellular blastoderm,
      trithorax RNA expression in D. virilis embryos is also confined to the posterior
      portion of the presumptive mesoderm. This finding supports the idea that the
      specific BX-C-related expression domain is an essential feature of the trithorax
      gene.

PMID- 8555105
TI  - Trans-regulation of thoracic homeotic selector genes of the Antennapedia and
      bithorax complexes by the trithorax group genes: absent, small, and homeotic
      discs 1 and 2.
AB  - Genes of the trithorax group appear to be required for the maintenance of
      expression of the homeotic selector genes of the Antennapedia and bithorax
      complexes. According to genetic criteria, the Drosophila melanogaster genes
      absent, small, or homeotic discs 1 and 2 (ash1 and ash2) are members of the
      trithorax group. In this paper we examine the consequences of ash1 and ash2
      mutations on the expression of homeotic selector genes in imaginal discs. The
      results of these experiments demonstrates that both ash1 and ash2 are trans
      regulatory elements of homeotic selector gene regulation. Hypomorphic ash1
      mutations cause variegated expression of Antennapedia, Sex combs reduced,
      Ultrabithorax, and engrailed. Complete loss of ash2 activity causes the loss of
      expression of Sex combs reduced in first leg imaginal discs, loss of expression
      of Ultrabithorax in third leg discs, and a late-patterned loss of expression of
      Ultrabithorax within haltere discs, yet has no effect on engrailed or
      Antennapedia expression. These results suggest that the range and action of
      trithorax group genes is varied and complex and argue against any model in which
      all of the products of the trithorax group act together in a single mechanism or
      complex.

PMID- 8555106
TI  - The Drosophila melanogaster tumor suppressor gene lethal(3)malignant brain tumor
      encodes a proline-rich protein with a novel zinc finger.
AB  - The lethal(3)malignant brain tumor [t(3)mbt] gene causes, when mutated, malignant
      growth of the adult optic neuroblasts and ganglion mother cells in the larval
      brain and imaginal disc overgrowth. Via overlapping deficiencies a genomic region
      of approximately 6.0 kb was identified, containing l(3)mbt+ gene sequences. The
      l(3)mbt+ gene encodes seven transcripts of 5.8 kb, 5.65 kb, 5.35 kb, 5.25 kb, 5.0
      kb, 4.4 kb and 1.8 kb. The putative MBT163 protein, encompassing 1477 amino
      acids, is proline-rich and contains a novel zinc finger. In situ hybridizations
      of whole mount embryos and larval tissues revealed l(3)mbt+ RNA ubiquitously
      present in stage 1 embryos and throughout embryonic development in most tissues.
      In third instar larvae l(3)mbt+ RNA is detected in the adult optic anlagen and
      the imaginal discs, the tissues directly affected by l(3)mbt mutations, but also
      in tissues, showing normal development in the mutant, such as the gut, the goblet
      cells and the hematopoietic organs.

PMID- 8555107
TI  - Drosophila MAP kinase kinase suppresses the vulvaless phenotype of lin-3, let-23
      and lin-45 mutations in Caenorhabditis elegans.
AB  - The vulva of the nematode Caenorhabditis elegans develops from the three vulval
      precursor cells (VPCs) that are induced by a signal from the gonadal anchor cell.
      This signal is thought to be mediated by a receptor tyrosine kinase (RTK) in the
      VPCs to a downstream signal transduction pathway. A mitogen-activated protein
      kinase kinase (MAPKK) has been found to be one of the major components of an RTK
      pathway in other organisms. We expressed a wild type and an activated cDNA of
      Dsor1, a Drosophila MAPKK, in each of the three vulvaless mutants lin-3, let-23
      and lin-45. The expression of an activated from of Dsor1 in each of the mutants
      effectively induced a normal, functional vulva, that is, suppressed the vulvaless
      phenotype. The wild type Dsor1 also suppressed albeit less effectively. These
      results suggest that a MAPKK is involved in the vulval induction of C. elegans.

PMID- 8555108
TI  - Involvement of Wnt-1 in the formation of the mes/metencephalic boundary.
AB  - Wnt-1, a putative signaling molecule, is required before the 7 somite stage
      (E8.5) for the development of midbrain structures in the mouse. We show here that
      Wnt-1 is also needed for the formation of a boundary between the mesencephalic
      and metencephalic domains of the neural tube. In embryos homozygous for the Wnt
      1sw allele, mesencephalic and metencephalic markers fail to segregate and the
      establishment of a straight limit of Otx-2 and Wnt-1 expression at the mid
      hindbrain junction is impaired. In addition, as observed previously in
      heterotopic mes/metencephalic transplantation experiments in avian embryos, Wnt-1
      expression is induced at the border of ectopic mes- and metencephalic islands
      observed in Wnt-1sw/sw mutants, suggesting that, in situ, interactions between
      mes- and metencephalic cells reinforce Wnt-1 expression at the boundary.

PMID- 8555109
TI  - Analysis of the genes involved in organizing the tail segments of the Drosophila
      melanogaster embryo.
AB  - The metameric organization of the Drosophila melanogaster tail is obscured by
      developmental events that partially suppress or fuse some of its regions. To
      better define the developmental origins and segmental identities in the tail of
      the Drosophila embryo, we documented expression patterns and mutant phenotypes of
      several genes that play important roles in its morphogenesis. We documented the
      domains of engrailed (en), Abdominal-B (Abd-B) and caudal (cad) expression in the
      tail region. The staining pattern of cut (ct) was used to correlate the embryonic
      sense organs with their respective positions on the larval cuticle. The en
      patterns in different Bithorax-Complex (BX-C) Abd-B morphogenetic (m) and
      regulatory (r) mutants demonstrated that Abd-B functions to, among other things,
      suppress embryonic ventral epidermal structures on the posterior side of A8 to
      A9. Ventral epidermal structures were not added back into the en pattern in r- or
      BX-C- mutants, indicating that although the BX-C functions extend through A10,
      other non-BX-C genes must be required for development of this segment.

PMID- 8555110
TI  - Polycomb and bmi-1 homologs are expressed in overlapping patterns in Xenopus
      embryos and are able to interact with each other.
AB  - The Polycomb group genes in Drosophila are involved in the stable and inheritable
      repression of gene expression. The Polycomb group proteins probably operate as
      multimeric complexes that bind to chromatin. To investigate molecular mechanisms
      of stable repression of gene activity in vertebrates we have begun to study
      Xenopus homologs of Polycomb group genes. We identified the Xenopus homologs of
      the Drosophila Polycomb gene and the bmi-1 gene. bmi-1 is a proto-oncogene which
      has sequence homology with the Polycomb group gene Posterior Sex Combs. We show
      that the XPolycomb and Xbmi-1 genes are expressed in overlapping patterns in the
      central nervous system of Xenopus embryos. However, XPolycomb is also expressed
      in the somites, whereas Xbmi-1 is not. We further demonstrate that the XPolycomb
      and Xbmi-1 proteins are able to interact with each other via conserved sequence
      motifs. These data suggest that also vertebrate Polycomb group proteins form
      multimeric complexes.

PMID- 8555111
TI  - Comparative analysis of chicken Hoxb-4 regulation in transgenic mice.
AB  - We cloned the chicken Hoxb-4 gene and performed in situ analysis to investigate
      conservation in patterns of expression between the chicken and mouse. The
      anterior boundaries of expression for both genes in segmented tissues, such as
      the hindbrain and paraxial mesoderm, map to the same rhombomere (r) (r6/r7) and
      somite (s) (s6/s7) limits, showing a direct correlation between expression of a
      specific Hox gene and patterning identical axial structures in both species.
      Given this similarity in expression we have tested the functional activity of cis
      regulatory regions from the chicken Hoxb-4 gene in transgenic mice to identify
      and map components conserved between the species. We identified enhancers which
      contain conserved blocks of sequence identity and which are necessary to mediate
      mesodermal and neural restricted patterns of expression. However, only the neural
      enhancer directs the proper anterior boundary of expression (r6/r7), indicating
      that only a subset of the underlying molecular components regulating Hoxb-4
      expression are functionally conserved between species.

PMID- 8555112
TI  - Mice lacking all isoforms of retinoic acid receptor beta develop normally and are
      susceptible to the teratogenic effects of retinoic acid.
AB  - Retinoic acids (RA) are vitamin A derivatives essential for normal embryonic
      development and viability of vertebrates. The RA signal is mediated by two
      distinct classes of receptors, RA receptors (RARs) and retinoid X receptors
      (RXRs). The RAR family is composed of three genes: RAR alpha, beta, and gamma.
      The expression of RAR beta gene is spatially and temporally restricted in certain
      structures in the developing embryo, suggesting that RAR beta could play specific
      roles during morphogenesis. Four isoforms of the RAR beta gene (beta 1-beta 4)
      are generated by differential usage of promoters and alternative splicing. It has
      recently been demonstrated that the RAR beta 2 isoform is dispensable for normal
      development. To ascertain the function of all RAR beta isoforms in vivo, we have
      generated a mutation that disrupts all isoforms of the RAR beta gene in the mouse
      by gene targeting in embryonic stem cells. Mice homozygous for the mutation are
      viable and fertile with no externally apparent abnormalities. During development,
      1/11 RAR beta mutant embryos showed fusion of the ninth and tenth cranial ganglia
      on both sides of the hindbrain. However, no obvious alterations in the spatial
      pattern of expression of Hoxb-1, Hoxb-4 and Hoxb-5 were observed in day 9.5 p.c.
      embryos. The RAR beta null mutation did not alter the pattern or extent of the
      limb and craniofacial malformations induced by RA excess, suggesting that RAR
      beta may not be mandatory to mediate the observed teratological effects of RA in
      these structures. These experiments demonstrate that RAR beta isoforms are not
      absolutely required for embryonic development and provide additional support to
      the concept of functional redundancy among members of the RAR family.

PMID- 8555113
TI  - Involvement of Notch-1 in mammalian retinal neurogenesis: association of Notch-1
      activity with both immature and terminally differentiated cells.
AB  - The Notch pathway is thought to define an evolutionarily conserved signaling
      mechanism that regulates the differentiation of immature cells through cells
      interactions. We have examined the expression of the Notch-1 receptor, the
      central element of this pathway, in the developing rat retina, where cell-fate
      choices depend upon a series of local cell interactions. Notch-1 immunoreactivity
      is associated with differentiating cells at different stages of retinal
      neurogenesis, suggesting that Notch-1 may play a role in the successive cell-fate
      determination which governs retinal development. In addition, the Notch-1
      immunoreactivity is detected in nuclei of postmitotic, differentiated neurons of
      the adult retina. Our observations raise the possibility that besides its role in
      the differentiation of immature cell populations Notch-1 activity may also be
      involved in the maintenance of the differentiated state.

PMID- 8555114
TI  - A single homeodomain binding site restricts spatial expression of Wnt-1 in the
      developing brain.
AB  - In this study we investigate the molecular mechanisms that are responsible for
      the restricted expression of Wnt-1 during embryogenesis. We report that a single
      homeodomain binding site, HBS1, within the Wnt-1 enhancer contributes to
      appropriate spatial expression of Wnt-1 in the developing nervous system. This
      HBS1 site may be required for repressing Wnt-1 expression in the developing
      forebrain since specific mutations of this site result in an extension of the
      rostral boundary of Wnt-1/lacZ staining in transgenic embryos. We further
      demonstrate that a subset of homeodomain proteins expressed in the forebrain
      (i.e., Dix2, Emx2) interact specifically with HBS1. These findings suggest that
      these (or related) homeodomain proteins may regulate expression of Wnt-1 during
      normal brain development by interacting with the HBS1 site in the Wnt-1 enhancer.

PMID- 8555115
TI  - The angiogenic potentials of the cephalic mesoderm and the origin of brain and
      head blood vessels.
AB  - We have used two molecular markers to label blood vessel endothelial cells and
      their precursors in the early avian embryo. One marker, called Quek1, is the
      avian homologue of the mammalian VEGF receptor flk-1 and the other is the MB1/QH1
      monoclonal antibody. Quek1 is expressed in a subset of mesodermal cells from the
      gastrulation stage. Quek1 positive cells later form blood vessel endothelial
      cells and express the MB1/QH1 antigen which is specific for endothelial and
      hemopoietic cells of the quail species. These two markers allowed us first to
      show that the cephalic paraxial mesoderm has angiogenic potentials which are much
      more extended than its trunk counterpart (the somites). Secondly, the origin of
      the endothelial cells lining the craniofacial and head blood vessels was mapped
      on the 3-somite stage cephalic mesoderm via the quail-chick chimera technique, in
      which well defined mesodermal territories are exchanged between stage-matched
      embryos of both species in a strictly isotopic manner. We found that the anterior
      region of the cephalic paraxial mesoderm is largely recruited to provide the
      forebrain and the upper face with their vasculature. This means that large
      volumes of tissues are vascularized by a discrete region of the cephalic
      mesoderm, the fate of which is otherwise to give rise to muscles. The widespread
      expansion of the angiogenic cells arising from the anterior paraxial mesoderm
      must be related to the high growth rate of the anterior region of the neural
      primordium, yielding the telencephalon and of the neural crest-derived facial
      structures which are themselves devoid of angiogenic potencies.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8555116
TI  - Distress and symptoms of posttraumatic stress disorder in abused women.
AB  - Emotional distress and symptoms of posttraumatic stress disorder (PTSD) were
      examined among women in psychologically abusive relationships. Women (N = 93)
      were divided into three groups (none, moderate, severe) according to scores on
      the violence subscale of the Severity of Violence Against Women Scales (Marshall,
      1992). All groups reported serious emotional distress on the Symptom Checklist 90
      Revised (Derogatis, 1983) dimensions (e.g. more so than 93% of the nonclinical
      norm for global distress). Psychoticism was the highest subscale for all groups.
      Most women (56%) suffered PTSD according to a subscale of the SCL90 (Saunders,
      Arata, & Kilpatrick, 1990). Difficulties with perception, memory, and motor
      functions (cognitive failure) more consistently predicted intrusive thoughts.
      PTSD scores, and attempted suicide than did women's attention to their inner
      thoughts and feelings (private self-consciousness), which was important for the
      sample and the subgroup that had sustained severe violence. Limitations and
      contributions are discussed as are different uses for conservative and inclusive
      measures of PTSD.

PMID- 8555117
TI  - A scale for identifying "Stockholm syndrome" reactions in young dating women:
      factor structure, reliability, and validity.
AB  - The factor structure, reliability, and validity of a 49-item scale designed to
      measure Stockholm Syndrome (also referred to as "traumatic bonding" and "terror
      bonding"), that is, bonding with an abusive partner, were assessed for college
      women in heterosexual dating relationships. Factor analysis identified three
      major factors: Core Stockholm Syndrome, characterized by cognitive distortions
      and other strategies for coping with abuse; Psychological Damage, marked by
      depression, low self-esteem, and loss of sense of self; and Love-Dependence,
      typified by the feeling that one cannot survive without one's partner's love. The
      scale and factors had excellent internal consistency and good test-retest
      reliabilities. They correlated negatively with the Marlowe-Crowne Social
      Desirability scale and positively with Horowitz, Wilner, & Alvarez' (1979) Impact
      of Event Scale, Hyler and Rieder's (1987) Borderline Personality Disorder Scale,
      Hatfield and Sprecher's (1986) Passionate Love Scale, and Straus' (1979) Verbal
      Aggression and Violence scales of the Conflict Tactics Scales.

PMID- 8555118
TI  - Violence in the marital dyad as a predictor of violence in the peer relationships
      of older adolescents/young adults.
AB  - This study used self-report of older adolescent/young adult children from a
      general college population to examine if violent parental conflict tactics
      predict the use of similarly violent tactics in the same-sex and opposite-sex
      peer relationships of offspring. Conflict Tactics Scale date from 256 subjects
      indicate that parental violence within the marital dyad is predictive of violence
      in both same-sex and opposite-sex peer relationships. Surprisingly high
      frequencies of violence were reported within parents' marriages and by subjects
      in their current peer relationships. Implications of these findings are
      discussed.

PMID- 8555119
TI  - Control, coping, and victimization in dating relationships.
AB  - This study examined the role of perceived control and coping in mediating the
      relationship between violent and nonviolent negative relationship events and
      women's experience of distress. Results based on the responses of 48 victims of
      dating relationship violence and 74 nonvictims indicated that perceived control
      was negatively related to distress for victims but not nonvictims. While both
      victims and nonvictims engaged in both problem- and emotion-focused coping, and
      different patterns of coping emerged for the two groups, appraisals of control
      were not related to choice of coping strategies for violent or nonviolent
      negative relationship events. Psychological distress was not significantly
      predicted by coping strategies or the interaction of control and coping for
      either type of event of for either group. These results suggest that control
      appraisals may be particularly important in reducing distress for victims.
      However, appraisals of perceived control may place them at increased risk for
      abuse in the long run, as victims are unlikely to be able to control the violence
      as it escalates in both severity and frequency over time.

PMID- 8555120
TI  - Relationship between multiple exposures to violence and coping strategies among
      African-American mothers.
AB  - This exploratory study examined the relationship between coping strategies of 136
      African-American mothers, their exposure to community violence, and their
      interpersonal victimization. It is suggested that the disproportionate
      victimization of African-American women produces a cumulative triple threat for
      those who live amidst conditions of community violence in the following manner:
      a) exposure through daily living in the midst of unpredictable community
      violence; b) exposure to violence from witnessing violence in the neighborhood;
      and c) exposure to violence from disproportionately high rates of personal
      victimization. The findings suggest that coping strategies are used
      differentially as a function of the amount of violence within the social context,
      and the education and financial resources of the mothers. Mothers who live in
      lower-violence areas with college education preferred activism as a coping
      strategy, whereas those in high-violence areas with comparable incomes and
      education preferred reliance on prayer and instituting safety practices. Coping
      strategies differed based on whether mothers had been physical victims and
      witnesses to violence or had no personal experience with violence. This study
      lays the groundwork for a model of exploring the impact of the cumulative effects
      of violence on African-American mothers parenting in urban America.

PMID- 8555121
TI  - Impact of sexual and nonsexual assault on secondary victims.
AB  - Much information has been collected on the effects of crime upon victims. Experts
      have spoken as well about the ripple effects of crime on those close to victims.
      To date, however, little empirical data are available to assess the impact of
      crime upon "secondary victims." Our research looks at the effects of crime on a
      sample of persons named by victims of sexual and nonsexual assault as their
      primary significant others (SOs). We found that distress experienced by SOs did
      not vary according to victim distress or according to whether the crime was a
      sexual or nonsexual assault. Female SOs, however, experienced greater fear of
      crime than male SOs. High levels of SO distress did not interfere with the
      ability of SOs to lend supportive actions, but were associated with higher levels
      of SO unsupportive behavior. Higher levels of unsupportive behavior were also
      more likely among SOs of sexual assault victims than among SOs of nonsexual
      assault victims. Clinical implications of the findings are discussed.

PMID- 8555122
TI  - [Guidelines for establishment of cultured cell lines and the reporting system.
      Japan Human Cell Society].

PMID- 8555123
TI  - [Establishment of a cisplatin-resistant new human endometrial adenocarcinoma cell
      line, Sawano cells].
AB  - A new human endometrial adenocarcinoma cell line, Sawano cells, was established
      from an endometrial adenocarcinoma from a 61-year-old woman and has been
      maintained in vitro for more than 2 years and 10 months. The cells were found to
      form a monolayer in a mosaic fashion and to tend to pile up. Population doubling
      time was 43.2 hours at the 10th generation. The modal chromosomal number of the
      cell fell in a diploid range. Histology of the tumor induced in athymic mice
      showed it to be a moderately differentiated adenocarcinoma which closely
      resembled the original human tumor. Estrogen and progesterone receptors were not
      demonstrated in the in vitro culture cells and in the tumors induced in nude
      mice, though they were positively demonstrated in the original tumor. The cells
      had intrinsic cisplatin-resistance (50% inhibition concentration:6.63
      micrograms/ml) at 120 hours of contact. We believe this cell line with help us to
      investigate the biological mechanisms of CDDP resistance.

PMID- 8555124
TI  - Early cholestasis in premature infants receiving total parenteral nutrition: a
      possible consequence of shock and hypoxia.
AB  - We report 18 premature infants (gestational age: 31.1 weeks +/- 2.6 [mean +/- SD]
      (range: 28-36]) with necrotizing enterocolitis (NEC) who developed total
      parenteral nutrition (TPN) associated cholestasis. Liver function tests were
      performed at the start of TPN (D1) and repeated once a week. Considering the date
      of cholestasis onset (direct bilirubin > 30 mumol/l and/or serum bile salts > 10
      mumol/l), the patients can be divided in two groups. The first group consisted of
      9 patients who had cholestasis at D1. In these patients shock and/or hypoxia
      occurred prior to D1 and were the only risk factors of cholestasis identified
      before D1. The second group consisted of 9 patients who developed cholestasis
      after D1 and in whom the cause of cholestasis was multifactorial (sepsis, lack of
      enteral feeding, shock and/or hypoxia). These results suggest that shock and/or
      hypoxia can be responsible for early cholestasis in premature infants. We
      conclude that shock and hypoxia should be considered when discussing TPN
      associated cholestasis.

PMID- 8555125
TI  - Follicular adenoma of the thyroid gland in children.
AB  - Follicular adenoma is the most frequent cause of a solitary thyroid nodule in
      children. We reviewed our own patient material and the literature and discuss
      etiology, available diagnostic methods, differential diagnosis, natural course
      and clinical management. In spite of the fact that the great majority of solitary
      thyroid nodules are benign, the treatment strategy is completely dominated by the
      risk for malignancy.

PMID- 8555127
TI  - The prognostic significance of biliary bilirubin conjugates in biliary atresia.
AB  - Nine patients with biliary atresia (BA) were investigated from the aspect of
      biliary bilirubin conjugates. They were classified arbitrarily into the good
      prognostic group in which jaundice disappeared (serum total bilirubin equal or
      below 1.0 mg/dl), and the poor prognostic group in which persistent jaundice was
      observed for more than 12 months. The ratio of biliary bilirubin diconjugate
      (BDC) increased in all patients of the two groups by the first month after
      operation. Although there was no significant difference in daily bilirubin
      excretion within 1-3 postoperative days, the BDC ratio in the good prognostic
      group was significantly higher than that in the poor prognostic group (p < 0.01).
      The study indicated that the ratio of BDC was an early prognostic determinant of
      BA patients. The prognosis of BA patients was much influenced by the ability of
      bilirubin conjugation in the early postoperative days.

PMID- 8555126
TI  - Innervation patterns in congenital biliary dilatation.
AB  - The innervation of choledochal cysts was studied to see if the distribution of
      innervating ganglion cells can be utilized as a possible indicator of the damage
      and dilatation process of choledochus. Specimens from 32 patients aged 1 month to
      12 years were stained by the immunoperoxidase method with neural tissue-specific
      antibodies, the innervating ganglion cells were counted and their number was
      correlated with the clinical severity, patient's age-at-surgery, and
      intraoperative cholangiographic and/or ERCP findings. In cystic dilatation, the
      total number of ganglion cells within the choledochal wall was significantly
      lower than in control specimens regardless of the diameter of the choledochal
      cyst, age-at-surgery, or clinical course. In fusiform dilatation, the total
      number of ganglion cells varied according to the severity of the clinical
      presentation, and the diameter of the fusiform choledochus increased in
      proportion to the patient's age-at-surgery. The distribution of innervating
      ganglion cells is thought to correlate quantitatively with the damage and
      dilatation process responsible for the choledochal cyst. These results may
      support a hypothesis that the pathogenesis of cystic dilatation proceeds
      antenatally or soon after birth, while that of fusiform dilatation begins after
      birth.

PMID- 8555128
TI  - Residual cavities after surgery for hepatic hydatid cysts--an ultrasonographic
      evaluation.
AB  - Ultrasonography has made it easier to diagnose precisely hepatic hydatid cysts,
      but the interpretation of images of residual cavities persisting long after the
      operation can be difficult. We reviewed the clinical histories of 22 children
      treated surgically for hepatic hydatid cysts at our hospital (1985-1992) to find
      clues to the proper attitude toward residual cavities. The children's mean age
      was 7.4 +/- 2.5 years. Fourteen children had single cysts (11 right and 3 left)
      and 8 children had multiple cysts, one of them 30 cysts (16 right and 14 left).
      The mean ultrasonographic diameter of the 44 cysts was 6.1 +/- 3 cm. Cystectomy
      with partial pericystectomy was performed in every case. Six months after
      operation, 29 cavities had disappeared, became calcified, or were substituted
      with fibrous scar tissue. The remaining 15 residual cavities had a mean diameter
      of 3 +/- 1 cm. The residual cavities exhibited little change at 12 months (2.8 +/
      1 cm), but at 18 months 9 had disappeared, 2 that increased in size and 4
      remained the same size. Of these 4 stable lesions, surgery performed in 2 found
      no cysts and 2 have been followed-up ultrasonographically for 5 years. This short
      series shows that ultrasonography is useful in the diagnosis and follow-up of
      residual cavities after surgery for hepatic hydatid cysts. Most residual cavities
      disappeared by 18 months. In the cavities that persisted, our findings suggest
      that surgical treatment is justified only when the cyst becomes larger on
      ultrasonography.

PMID- 8555129
TI  - Rectal suction biopsy: can it be sufficient to diagnose neuronal intestinal
      dysplasia?
AB  - Rectal suction biopsy is the diagnostic procedure of choice in aganglionosis even
      if only mucosal tissue is obtained. In neuronal intestinal dysplasia it is
      essential to include parts of the submucous layer. Therefore some biopsies are
      unsuitable because they lack submucous tissue. In a retrospective analysis (1991
      1993) this occurred in 34.9% of our biopsies. These samples were taken without
      attention to the level of suction. Prospectively we compared suction biopsies
      taken by a standard suction level (250-300 cm water column) with excision
      biopsies taken by scissors under speculum exposure in ten consecutive patients.
      Submucosa was missed in only one biopsy each, but two excision biopsies were made
      useless by mechanical traumatization. We conclude a correctly practised rectal
      suction biopsy still remains the procedure of choice for diagnostic screening in
      malformations of the enteric nervous system.

PMID- 8555130
TI  - A case of asymptomatic passage per-rectum of a fractured redundant peritoneal
      catheter from a ventriculo-peritoneal shunt.
AB  - Over 30 cases of perforation of the bowel have been described by intact
      peritoneal catheters of ventriculo-peritoneal and some lumbo-peritoneal shunts.
      Because of this risk it is advocated that redundant or free fractured or
      disconnected peritoneal catheters should if possible be removed from the abdomen;
      although we could find no reports of morbidity from such free fragments. We
      describe a case of extrusion per-rectum of a redundant fractured peritoneal
      catheter which it had not been possible to retrieve after a revision procedure.

PMID- 8555131
TI  - Prophylactic antibiotics in uncomplicated appendicitis during childhood--a
      prospective randomised study.
AB  - 544 children operated upon for uncomplicated appendicitis were randomised into
      three groups. Group I received no antibiotics, patients in Group II were
      administered one single pre-operative dose of metronidazole (10 mg/kg) and
      patients in Group III received both both metronidazole (20 mg/kg) and cefuroxime
      (50 mg/kg) in a single preoperative dose. The rate of infectious complications in
      Group I was 6.3% but only 2.1 and 2.3 in Groups II and III, respectively. Among
      patients with a normal appendix or patients with simple appendicitis there was no
      difference in the rate of post-operative infections between the three different
      groups. However, in patients with gangrenous appendicitis the rate of
      postoperative infections was significantly lower in the two groups who received
      preoperative antibiotics (1.8% and 3.0% respectively) than in the group receiving
      no prophylactic antibiotics (infection rate 14%). It is concluded that a single
      preoperative dose of metronidazole significantly decreases the rate of
      postoperative infectious complications in children with appendicitis. No further
      improvement could be demonstrated if cefuroxime against aerobic organisms was
      added.

PMID- 8555132
TI  - Scattered radiation in a neonatal surgical unit.
AB  - We studied the doses of "scattered" received by neonates in a Neonatal Surgical
      Unit by placing thermoluminescent dosemeters in various positions expect the
      direct beam. Doses of "scattered" radiation received by neonates as a results of
      exposure of their neighbours to X-ray examinations were found to be negligible.
      Sick neonates need not be moved from their neighbours undergoing exposure to X
      rays.

PMID- 8555133
TI  - Preoperative diagnostics and surgical management of tertiary hyperparathyroidism
      after chronic renal failure in a child.
AB  - Although hyperparathyroidism if a rare condition in young children, the pediatric
      surgeon is asked occasionally to participate in the management of a child with
      parathyroid disease. In this paper we report on a girl with global
      glomerulosclerosis, an unsuccessful renal transplantation and a long-term
      peritoneal dialysis, who developed an autonomous hyperparathyroidism. Emphasis is
      placed on the preoperative diagnosis and surgical management in children.

PMID- 8555134
TI  - Central hypoventilation syndrome associated with ganglioneuroblastoma.
AB  - In this paper the authors describe a case of central hyperventilation syndrome
      associated with a neural crest tumor. The girl had several apneic spells at the
      age of three years. She had a tracheostomy and mechanically assisted ventilation
      while asleep. Routine hematologic studies and chest x-ray were within normal
      limits. Computerized tomography scan and magnetic resonance imaging revealed a
      left paraspinal mass suggestive of a neural crest tumor. This mass was excised
      and histopathologic findings of this tumor revealed a ganglioneuroblastoma.

PMID- 8555135
TI  - Mediastinal stabilization by an expansion prosthesis in postoperative congenital
      diaphragmatic hernia with severe pulmonary hypoplasia.
AB  - The authors illustrate a case of right neonatal congenital diaphragmatic hernia
      (CDH) of Bochdalek with major pulmonary hypoplasia and postoperative massive
      mediastinal displacement to the right, leading to tracheal compression and
      recurrent respiratory distress at every attempt to wean the infant from the
      ventilator. Mediastinal stabilization was obtained by placing an expansion
      prosthesis (of the cutaneous type) in the right hemithorax, to prevent
      mediastinal obstruction of the main airways. This procedure may prove to be an
      original and efficient solution for the critical postoperative respiratory
      obstruction due to severe pulmonary hypoplasia and mediastinal mass effect in the
      newborn with CDH. However, this may not prevent progressive scoliosis, a serious
      problem frequently seen in the absence of one lung.

PMID- 8555136
TI  - Treatment of esophageal varices by endoscopic ligation in children.
AB  - Endoscopic variceal ligation (EVL) is an alternative technique to endoscopic
      variceal sclerotherapy (EVS) to treat esophageal varices. This method consists of
      mechanical ligature and thrombosis of varices using elastic rubber rings. During
      an 11-month period, nine pediatric patients with esophageal varices secondary to
      portal hypertension were treated by EVL. Extrahepatic portal vein obstruction was
      the cause of portal hypertension in 5 patients and in 4 cases the cause was
      intrahepatic disease. The average age of the patients was 8 years (range: 2-15).
      Five patients had bled from esophageal varices previously. Two were actively
      bleeding at the time of the procedure. Endoligature was performed
      prophylactically in four patients. Fifty varix ligations were performed in 26
      separate sessions. In children older than ten years, EVL was performed under
      intravenous sedation. Two mild rebleeds have occurred in this group and responded
      to repeated ligature. Varices were reduced in grade in all patients. Six patients
      achieved variceal eradication. Recurrence of varices was not encountered. No
      major complications occurred and there were no treatment failures. These early
      results suggest that endoscopic ligation is a safe and effective method for the
      control of esophageal varices in children.

PMID- 8555137
TI  - Myoepithelial hamartoma of the ileum: a rare cause of intestinal intussusception
      in children.
AB  - Herein we present a case report of a 2-year-old male child who suffered an
      ileocecal intussusception not reduced by pneumoenema. At the apex of the
      intussusception there was a 2 cm tumor. The pathologic diagnosis was
      myoepithelial hamartoma. In a review of the literature we could find no previous
      reference to myoepithelial hamartomas located in distal ileum causing
      intussusception in children.

PMID- 8555138
TI  - Pancreaticoduodenectomy in childhood for rare pancreatic ductal anomalies--case
      reports.
AB  - In the past 9 years, 3 children suffering rare pancreatic disorders have
      undergone cephalic pancreaticoduodenectomy (Whipple procedure) required after the
      failure of initial conservative treatments. Ductal anomalies such as pancreas
      divisum or predominant Santorini duct can be managed conservatively (especially
      by papillotomy of the minor papilla), unless the extent of the fibrotic lesions
      of the pancreas jeopardizes the final evolution of the pancreatic disease.
      Intrapancreatic gastric duplications remain extremely rare. Even to-day,
      diagnosis was made only on pathologic specimens after radical surgery. Better
      knowledge of this rare pathology, with emphasis on its radiological features, may
      help better assessment. Hemoductal pancreatitis is evocative of the coexistence
      of gastric duplication and pancreatic aberrant duct. However, when fibrotic and
      necrotic changes in the duodenopancreatic region are considerable, assessment of
      this anomaly becomes difficult. Radical though it is, pancreaticoduodenectomy may
      be necessary to treat cephalic pancreatic lesions in childhood after the failure
      of reasonable attempts of conservative treatment.

PMID- 8555139
TI  - Selective splenic artery embolization or use of polyglycolic acid mesh in
      children with severe splenic trauma.
AB  - Children with splenic trauma are managed conservatively in most circumstances,
      and the need for surgical intervention is very rare. When surgical exploration in
      mandatory, splenic preservation is a worthwhile objective, using various suture
      methods, biomaterials, or resorbable prostheses. We present our experience over
      the past year with 5 severe splenic injuries. Three of these patients were
      treated operatively with a resorbable mesh, while the other two were managed
      percutaneously by selective embolization of the splenic artery under fluoroscopic
      control. We describe the embolization technique with its advantages, good outcome
      with low morbidity, and low economic and social cost.

PMID- 8555140
TI  - Gallbladder carcinoma in an achondroplastic boy.
AB  - Carcinoma of the gallbladder in an extremely rare tumor in childhood. We have
      found only five cases in the literature. Most of them were associated with an
      ethnic group - The Navajo Indians - who are known to have high incidence of
      gallbladder disease. We report here on the exceptional presence of this type of
      tumor in a child, who also had achondroplasia. This, as far as we can determine,
      is the first such case ever reported.

PMID- 8555141
TI  - Internationalism in oral and maxillofacial surgery.

PMID- 8555142
TI  - Fixture stability and nerve function after transposition and lateralization of
      the inferior alveolar nerve and fixture installation.
AB  - Twenty-four posterior mandibular segments in 18 patients were operated on placing
      implants after mobilisation of the neurovascular bundle. Two different surgical
      techniques, transposition and lateralization was used. The overall survival rate
      of fixtures was 92.1%. Performing lateralization resulted in 100% success, while
      transposition resulted in 80% stable fixtures in the involved segments. The mean
      time to full restoration of nerve function was 3.8 weeks after lateralization and
      5.7 weeks after tranposing the nerve. Three patients exhibited persisting slight
      hyposthesia, but all, subjectively negligible disturbances in nerve function.

PMID- 8555143
TI  - Patient satisfaction with implant-retained mandibular overdentures. A comparison
      with new complete dentures not retained by implants--a multicentre randomized
      clinical trial.
AB  - OBJECTIVES: The aim of this study was to establish the treatment outcome of full
      denture treatment with or without implant support, in which the outcome
      assessment focuses on the patient's subjective evaluation ('denture
      satisfaction'). DESIGN: A multicenter randomized clinical trial. SUBJECTS: Thirty
      two men and 118 women (mean age 56 +/- 9, range 35-84 years) participated in the
      study. The mean height of the mandible was 13 +/- 2 mm, measured on a lateral
      cephalometric radiograph. The patients were randomly assigned to either a group
      treated with implant-retained mandibular overdentures and a new maxillary
      denture, or to a control group treated with a new set of complete dentures. MAIN
      OUTCOME MEASURES: Denture satisfaction was assessed using questionnaires focusing
      on denture-related complaints and 'a general satisfaction rate'. RESULTS: Based
      on the baseline data, from the 'denture complaints' questionnaire six
      interpretable factors could be extracted. One factor did not vary following
      treatment and was excluded from the outcome analysis. At the 1-year evaluation
      three out of five factors showed significantly better scores for the group
      treated with implants than for the control-group. The same was found for the
      general satisfaction rate. CONCLUSION: For patients with a severely resorbed
      mandible, overdentures retained by dental implants appear to provide a more
      satisfactory solution to their denture-related problems.

PMID- 8555144
TI  - A new implant site in iliac crest bone graft for retention of orbital epistheses:
      a preliminary report.
AB  - Osseointegrated percutaneous implants were placed at different sites of the
      facial skeleton to improve the retention of facial prostheses. Based on four
      cases a new implant position in autogenous bone grafts for retention of orbital
      restorations is described. As a first step an autogenous iliac bone graft was
      transplanted into the orbit. After a minimum interval of 3 months endosseous
      implants were placed into the grafted bone in axial direction in the middle of
      the orbit. A third operation several months later uncovered the implants. Using
      single free-standing rare earth magnetic attachments the orbital episthesis or
      the eye prosthesis was reliably stabilized. In all cases the bone grafts were
      integrated at the host site. Nine implants with a follow-up period of 4-66 months
      have been placed of which one was lost. The patients experienced subjective and
      objective improvement. Indications and advantages of the method are discussed.

PMID- 8555145
TI  - The correlation between training and skill of the surgeon and reoperation rate
      for persistent cleft palate speech.
AB  - The correlation between the surgeons training and skill and the speech after
      primary repair was tested using the reoperation rate as a measure for success in
      439 cleft palate/cleft lip and palate (CP/CLP) patients operated at the average
      age of 22 months by 4 specialists and 4 residents. The reoperation rate for
      residents was 11-60% (av. 36) and for specialists 13-31% (av. 19). The relative
      reoperation rates in CP/CLP were 20/19% for specialists but 35/38% residents. In
      groups consisting of the four with the best (A) and the four with the worst
      results (B) the reoperations rate in group A was 16% for CP and 13% for CLP, but
      in group B 37/44%. As the residents became specialists, the degree of their
      improvement varied greatly. Thus both the training and skill are important for
      the patients speech, but they are not necessarily synonymous terms.

PMID- 8555146
TI  - Bilateral multifocal canalicular adenomas of buccal minor salivary glands: a case
      report.
AB  - Although the incidence of multifocal epithelial tumours of the minor salivary
      glands is very low, canalicular adenoma not infrequently presents as a multifocal
      lesion, usually in the upper lip. We present an unusual case of bilateral
      multifocal canalicular adenomas of the buccal mucosa in a woman aged 75 years.

PMID- 8555147
TI  - Subacute necrotising sialadenitis: a new entity?
AB  - Subacute necrotising sialadenitis (SANS) has recently been reported as a possible
      separate disease of the palatal salivary glands. Only 12 cases have been reported
      to our knowledge. We describe the clinical and histopathological findings of
      three new cases, and conclude that it is unlikely that SANS is a disease in its
      own right.

PMID- 8555148
TI  - Surgical treatment of stage I and II oral squamous cell carcinomas: analysis of
      causes of failure.
AB  - Sixty-one patients with stage I and II squamous cell carcinomas of the oral
      cavity treated by surgery alone were analysed to investigate treatment outcome,
      pattern of failure, and occurrence of second malignant neoplasms. The disease
      recurred or developed lately in 11 patients. The ipsilateral neck was the most
      common site of failure. Salvage treatment was successful in only three of these
      patients. Occult neck metastasis was found in 31% of patients with T2 tumours.
      Second malignant neoplasms developed in 20 patients and were the cause of death
      in 8 patients. In conclusion, locoregional control of stage I and II oral
      carcinomas is achieved by surgery alone. Elective neck dissection is required for
      patients with stage II tumours, showing a high risk of lymph node metastasis in
      histology.

PMID- 8555149
TI  - Tortuosity of the lingual artery and coronary atherosclerosis.
AB  - In a series of 69 human cadavers (age range 18-95 years), the tortuosity of the
      lingual artery and its association to age, sex, death of cardiovascular disease
      and general atherosclerotic state as assessed at necropsy were studied. The
      tortuosity increased significantly with age, but there were no sex differences.
      Within the three age groups there were no significant associations between
      arterial tortuosity and death from cardiovascular disease or general
      atherosclerotic state.

PMID- 8555150
TI  - Healing of experimentally created defects: a review.
AB  - Within cranio-maxillofacial surgery and orthopedic surgery a bone graft or a bone
      substitute is required to recontour or assist bony healing in repair of osseous
      congenital deformities, or in repair of deformity due to trauma or to surgical
      excision after elimination of osseous disease processes exceeding a certain size.
      An autogenous bone graft is the optimal material of choice, however its use is
      problematic due to donor site morbidity, sparse amounts and uncontrolled
      resorption. Immunological responses and risk of viral contamination of allogenous
      and xenogenous bone materials make the use of these materials questionable.
      Healing and degradation of alloplastic materials are inconsistent with subsequent
      restricted use. The principle of guided tissue regeneration excluding soft tissue
      cells from a certain area is not alone sufficient to insure complete bony
      healing. Recombinant bone morphogenetic proteins have with success been added as
      adjuncts to already known biomaterials. In the future, inductive materials
      together with a suitable carrier and a biodegradable membrane may be the choice
      of bone substitute used within cranio-maxillofacial and orthopaedic surgery.

PMID- 8555151
TI  - Screening for syphilis in patients with carcinoma of the tongue.
AB  - The oral signs of syphilis have been comprehensively described and can be
      identified at each stage of the infection. Despite the historical recognition
      that inadequately treated or untreated syphilitic leukoplakia may undergo
      malignant transformation, many surgical units no longer routinely screen patients
      presenting with malignant or premalignant lesions. In this study, five of the 63
      patients (8%) who presented with neoplasms of the tongue reacted to syphilis
      antibodies. These results indicate that syphilis is still prevalent in this group
      of patients and suggest that serological investigations may be warranted in the
      initial assessment of all patients with oral cancer.

PMID- 8555152
TI  - A new technique for the construction of interocclusal wafers in orthognathic
      surgery.

PMID- 8555153
TI  - An alternative method of intraoperative skin retraction: the Walton fish hook.
AB  - A simple and versatile means of skin flap retraction is presented. The method
      uses blunt hooks made from stainless steel wire with traction provided by elastic
      bands. The Walton fish hook is routinely used to assist in head and neck
      dissections.

PMID- 8555154
TI  - Reconstruction of cutaneous-pharyngeal fistula in two layers using microvascular
      free flap (a preliminary report)

PMID- 8555155
TI  - Citation for the presentation of the 1995 De Puy Surgical Prize to Mr Leo
      Stassen.

PMID- 8555156
TI  - Referred otalgia: an old lesson.

PMID- 8555157
TI  - Midfacial trauma.

PMID- 8555158
TI  - Incidence oral cancer in Scotland 1971-1989.

PMID- 8555159
TI  - A modified miniplate for use in malar complex fractures.

PMID- 8555160
TI  - Surgical audit system.

PMID- 8555161
TI  - Direct measurement of the aspartic acid 26 pKa for reduced Escherichia coli
      thioredoxin by 13C NMR.
AB  - Because of interference from the pH-dependent behavior of nearby groups in the
      active site of Escherichia coli thioredoxin, the pKa of the buried carboxyl group
      of the aspartic acid at position 26 has been difficult to quantitate. We report a
      direct measurement of this pKa using an NMR method utilizing the correlation
      between the C beta H proton resonances and the 13CO of the titrating carboxyl
      group. The experiments show unequivocally that the pKa is 7.3-7.5, rather than
      the value of 9 or greater recently proposed by Wilson, N. A., et al. [(1995)
      Biochemistry 34, 8931-8939]. The assignment of the titrating resonances to Asp 26
      is unambiguous: the values of the C beta H chemical shifts correspond exactly to
      those of Asp 26, and their titration in the pH range 5.7-10.0 is the same as that
      observed previously for the proton resonances alone. In addition, the chemical
      shift of the carboxyl 13C resonance at pH 5.7 is upfield of those of the other
      carboxyl and carboxamide resonances, diagnostic for a protonated carboxyl group.
      The resonances assigned to Asp 26 are the only ones that titrate in the pH range
      5.7-10.5. None of the other aspartate and glutamate residues in the molecule are
      titrated in this pH range, consistent with their positions on the surface of the
      molecule. The pKa measured for Asp 26 in reduced thioredoxin is identical within
      experimental error to that measured in the oxidized form of the protein. This is
      significant for the reductive mechanism of thioredoxin: the buried salt
      bridged/hydrogen-bonded side chains of Asp 26 and Lys 57 are likely to contribute
      to the facility of the reaction by providing a convenient source and sink for
      protons in the hydrophobic environment of the complex between thioredoxin and its
      substrates.

PMID- 8555162
TI  - Rates of reaction of indoleacetic acids with horseradish peroxidase compound I
      and their dependence on the redox potentials.
AB  - The rates of reaction of seven indole-3-acetic acid derivatives with horseradish
      peroxidase compound 1 at pH 5 were measured by stopped flow, and the reduction
      potentials and pKa of their radical cations were determined by pulse radiolysis.
      Reasonable correlation of these properties with Hammett substituent parameters
      was found, but not with Brown-Okamoto (theta +) parameters. The rates of reaction
      with compound I correlate well with the reduction potentials under the same
      conditions, with rates of reaction that increase by ca. 2.5 orders of magnitude
      with a 100 mV decrease in the reduction potential. This relationship is in
      agreement with that previously estimated for the reaction of compound I with
      phenols and anilines, suggesting that the rate of reaction depends solely on the
      reduction potential of the substrate radical, even for compounds of dissimilar
      structure.

PMID- 8555163
TI  - Covalent attachment of Arc repressor subunits by a peptide linker enhances
      affinity for operator DNA.
AB  - By designing a recombinant gene containing tandem copies of the arc coding
      sequence with intervening DNA encoding the linker sequence GGGSGGGTGGGSGGG, the
      two subunits of the P22 Are repressor dimer have been covalently linked to form a
      single-chain protein called Arc-L1-Arc. The 15-residue linker joins the C
      terminus of one monomer to the N-terminus of the second, a distance of
      approximately 45 A in the Arc-operator cocrystal structure. Arc-L1-Arc is
      expressed at high levels in Escherichia coli, with no evidence of degradation or
      proteolytic clipping of the linker, and is more active than wild-type Arc in
      repression assays. The purified Arc-L1-Arc protein has the molecular weight
      expected for the designed protein and unfolds cooperatively, reversibly, and with
      no concentration dependence in thermal-denaturation studies. Arc-L1-Arc protects
      operator DNA in a manner indistinguishable from that of wild-type Arc in DNase I
      and copper-phenanthroline footprinting studies, but the covalent attachment of
      the two monomers results in enhanced affinity for operator DNA. Arc-L1-Arc binds
      operator DNA half-maximally at a concentration of 1.7 pM, compared with the wild
      type value of 185 pM, and also binds DNA fragments containing the left or right
      operator half-sites more tightly than wild type. Because wild-type Arc is
      monomeric at sub-nanomolar concentrations and must dimerize before binding to the
      operator, it was anticipated that Arc-L1-Arc would exhibit a lower half-maximal
      binding concentration. However, even when the change from a monomeric to a
      dimeric species is taken into account, the affinity of Arc-L1-Arc for operator
      and half-operator DNA is greater than the wild-type affinity. This tighter
      binding appears to result from slower dissociation, as Arc-L1-Arc DNA complexes
      with full or half-site operators dissociate at rates 5-10 times slower than the
      corresponding Arc--DNA complexes. Hence, the activity of the designed Arc-L1-Arc
      protein is substantially increased relative to wild-type Arc in a variety of
      assays.

PMID- 8555164
TI  - Conservation in evolution for a small monomeric phenylalanyl-tRNA synthetase of
      the tRNA(Phe) recognition nucleotides and initial aminoacylation site.
AB  - We previously showed that yeast mitochondrial phenylalanyl-tRNA synthetase (MSF
      protein) is evolutionarily distant to the cytoplasmic counterpart based on a high
      degree of divergence in protein sequence, molecular mass, and quaternary
      structure. Using yeast cytoplasmic tRNA(Phe) which is efficiently aminoacylated
      by MSF protein, we report here the tRNA(Phe) primary site of aminoacylation and
      the identity determinants for MSF protein. As for the cytoplasmic phenylalanyl
      tRNA synthetase (Sampson, J. R., Di Renzo, A. B., Behlen, L. S., & Uhlenbeck, O.
      C. (1989) Science 243, 1363-1366), MSF protein recognizes nucleotides from the
      anticodon and the acceptor end including base A73 and, as shown here, adjacent G1
      C72 base pair or at least C72 base. This indicates that the way of tRNA(Phe)
      binding for the two phenylalanine enzymes is conserved in evolution. However,
      tRNA(Phe) tertiary structure seems more critical for the interaction with the
      cytoplasmic enzyme than with MSF protein, and unlike cytoplasmic phenylalanyl
      tRNA synthetase, the small size of the monomeric MSF protein probably does not
      allow contacts with residue 20 at the top corner of the L molecule. We also show
      that MSF protein preferentially aminoacylates the terminal 2'-OH group of
      tRNA(Phe) but with a catalytic efficiency for tRNA(Phe)-CC-3'-deoxyadenosine
      reduced 100-fold from that of native tRNA(Phe), suggesting a role of the terminal
      3'-OH in catalysis. The loss is only 1.5-fold when tRNA(Phe)-CC-3'-deoxyadenosine
      is aminoacylated by yeast cytoplasmic PheRS (Sprinzl, M., & Cramer, F. (1973)
      Nature 245, 3-5), indicating mechanistic differences between the two PheRS's
      active sites for the amino acid transfer step.

PMID- 8555165
TI  - Effects of circular permutation on the cis-cleavage reaction of a hepatitis delta
      virus ribozyme: application to trans-acting ribozyme design.
AB  - In this study we investigated the effects of the relocation of the wild type
      termini on the folding of a cis-cleaving RNA Rz 1 that was modified from the
      autolytic domains of hepatitis delta virus (HDV) RNA. Ten circularly permuted
      (CP) isomers of this ribozyme were synthesized. The structure homogeneity of RNA
      molecules, the molar ratio of the active species that undergoes cis-cleavage, and
      the rate of cis-cleavage were examined for each construct. CP isomers with new
      termini in H1 or at the junction of H2-H3, H1-J1/4, J1/4-H4, or H4-J4/2 of the
      proposed pseudoknot-like structure were inactive. The single breaks of
      phosphodiester bond in H2, J1/2, Lp4, and at the 3'-end of Lp3 decreased but did
      not abolish autolytic activity. The structural heterogeneity of RNA molecules may
      account for the limited cis-cleavage of the latter three isomers. The findings of
      circular permutation analysis were used as the basis for designing an active
      trans-cleaving ribozyme by dividing the cis-cleaving ribozyme into two subdomains
      at J1/2 and Lp4. The ribozyme subdomain catalyzed the site-specific cleavage of
      the circularly permuted composite substrate RNA in trans. Thus, the structure of
      HDV autolytic domain could be re-formed after two subdomains were associated
      through the base-pairing interactions of H1, H2, and H4.

PMID- 8555166
TI  - Effect of human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein on HIV
      1 reverse transcriptase activity in vitro.
AB  - Conversion of human immunodeficiency virus type 1 (HIV-1) genomic RNA to viral
      DNA is a requisite step in the virus life cycle. This conversion is catalyzed by
      reverse transcriptase (RT) associated with a large nucleoprotein complex composed
      of several viral proteins including nucleocapsid (NC). To better characterize the
      biochemical mechanisms of viral DNA synthesis, we overexpressed and purified
      recombinant HIV-1 NC and studied its effect on the activity and processivity of
      HIV-1 RT during polymerization of HIV-1 template sequences in vitro. The effect
      of NC on steady-state RT activity was dependent on the order of addition of
      reaction components. Addition of NC prior to formation of RT-primer.template-dNTP
      ternary complexes inhibited primer extension and reduced total product yields by
      slowing steady-state RT turnover. In contrast, addition of NC to preformed
      ternary complexes resulted in efficient primer extension and increased RT
      processivity at specific DNA template sites. NC stimulated polymerization (2-4
      times) through eight of 13 sites examined in the cRRE region of HIV-1 env and
      increased the rate of polymerization through the D3/CTS region of HIV-1 pol 10
      times. The data suggest that NC affects RT processivity by facilitating
      polymerization through regions of template secondary structure. Thus, NC
      functions as a single-strand binding (SSB)-like accessory replication factor for
      RT in vitro and may be part of a multicomponent retroviral replication complex.

PMID- 8555167
TI  - Transition state structure of Salmonella typhimurium orotate
      phosphoribosyltransferase.
AB  - Orotate phosphoribosyltransferase (OPRTase) catalyzes the magnesium-dependent
      conversion of alpha-D-phosphoribosylpyrophosphate (PRPP) and orotate to orotidine
      5'-monophosphate (OMP) and pyrophosphate. We have determined kinetic isotope
      effects on the reaction of OMP with pyrophosphate and with the pyrophosphate
      analog phosphonoacetic acid. In the latter case, full expression of the kinetic
      isotope effects allowed us to calculate the structure of the transition state for
      the pyrophosphorylytic reaction. The transition state resembles a classical
      oxocarbonium ion. Using the recently reported three-dimensional structures of the
      OPRTase-OMP (Scapin et al., 1994) and the OPRTase-PRPP complexes (Scapin et al.,
      1995a), we have modeled the calculated transition state structure into the active
      site of OPRTase. We propose a detailed chemical mechanism which is consistent
      with these results.

PMID- 8555168
TI  - Asp537 and Asp812 in bacteriophage T7 RNA polymerase as metal ion-binding sites
      studied by EPR, flow-dialysis, and transcription.
AB  - Asp537 and Asp812 are essential in the catalytic mechanism of T7 RNA polymerase.
      The mutants D537N and D812N have no detectable activity whereas the mutants D537E
      and D812E have significantly reduced activity relative to the wild-type. The
      hypothesis that these two amino acids act as metal-binding ligands has been
      tested using EPR with Mn2+ as the metal ion. Mn2+ is able to substitute for Mg2+
      in transcription by T7 RNAP on templates containing the T7 promoter. Mg2+ and
      Mn2+ compete for binding sites, with the former having lower affinity. Mn2+
      binding to the wild-type enzyme and the mutants D537N, D812N, D537E, D812E, and
      Y649F was measured over the concentration range of 25 microM to 1.5 mM. The data
      were analyzed by nonlinear least-squares fits to the binding isotherms, and the
      analysis gave approximately two Mn(2+)-binding sites in all cases and a Kd for
      the wild-type of approximately 340 microM. The Kd value for the mutant Y639F, in
      which Asp537 and Asp 812 are not mutated, is comparable to the value for the wild
      type. Mn2+ binding to the double mutants, D537N/D812N and D537E/D812E, appears to
      be nonspecific. The Kd values of the Asp-->Asn mutants are only 2-5 times larger
      than the value for the wild-type, in contrast to the drastic diminution of
      enzymatic activity in the mutants. The geometry of metal binding to these Asp
      residues may be crucial in determining the catalytic competence. Mn2+ binding to
      the wild-type enzyme in the presence of nucleotides, measured by flow dialysis,
      is characterized by two Mn(2+)-binding sites with a Kd value of ca. 150 microM.
      The similarity in values of Kd with and without nucleotide suggests that
      nucleotides do not have a drastic effect on Mn2+ binding. Our results indicate
      that monodentate carboxylate oxygens of both conserved Asp residues bridge the
      two metal ions.

PMID- 8555169
TI  - Position-specific effects of base mismatch on mammalian topoisomerase II DNA
      cleaving activity.
AB  - To further define the nucleic acid determinants of DNA site recognition by
      mammalian topoisomerase II, base mismatch effects on the enzyme DNA cleavage
      activity were determined in a 36-bp synthetic oligonucleotide corresponding to
      SV40 DNA. DNA cleavage sites induced by topoisomerase II without or with the
      antitumor drugs teniposide, idarubicin, or amsacrine were mapped using sequencing
      gels. Selected mismatches were studied, and always one of the two strands had the
      wild-type sequence. The effects of base mismatches were independent from the
      studied drugs. Mismatches introduced at the -4, -3, -2, or -1 positions, relative
      to the enzyme cleavage site, often abolished, or much reduced, DNA cleavage,
      whereas those at +1 and +2 positions often increased DNA breakage or were without
      influence. Mismatches at more distant positions, e.g., -7, -8, etc., had no
      effect. Those at positions -5 and -6 sometimes increased cleavage levels. These
      effects were always observed at sites already cleaved in the wild-type oligomer;
      new sites of cleavage were not induced by the studied mismatches. These results
      were obtained both for the native murine topoisomerase II and for the two
      recombinant human isozymes. No difference between topoisomerases II alpha(p170)
      and beta(p180) was seen in their response to mismatches. The results demonstrate
      that topoisomerase II recognition of the DNA site of cleavage requires fully
      paired nucleotides at the 3' terminus. Nevertheless, similarly to other DNA
      strand transferase enzymes, both topoisomerase II isoforms may have a sequence
      specific nicking activity at the 5' side of unpaired bases.

PMID- 8555170
TI  - Manganese(II)-dependent extradiol-cleaving catechol dioxygenase from Arthrobacter
      globiformis CM-2.
AB  - A manganese-dependent 3,4-dihydroxyphenylactate 2,3-dioxygenase from Arthrobacter
      globiformis strain CM-2 (MndD) cloned in Escherichia coli has been purified to
      homogeneity. Sedimentation equilibrium analysis indicates an alpha 4
      homotetrameric holoenzyme structure (4 x 38,861 Da). Steady-state kinetic
      analysis of MndD with a variety of substrates and inhibitors yields very similar
      relative rates to the known Fe(II)- and Mn(II)-dependent 3,4
      dihydroxyphenylacetate 2,3-dioxygenases from Pseudomonas ovalis and Bacillus
      brevis, respectively. Yet, unlike the Fe(II)-dependent enzyme, MndD retains
      almost all activity in the presence of H2O2 and CN- and is inactivated by Fe(II).
      ICP emission analysis confirms the presence of 3.0 +/- 0.2 g-atoms Mn (and only
      0.7 +/- 0.2 g-atoms Fe) per tetrameric holoenzyme molecule. Comparison of MndD
      samples with varying metal content, including an apo and partial-apo enzyme
      preparation, shows a strong positive correlation between specific activity and Mn
      content. EPR spectra of MndD as isolated exhibit a nearly isotropic g = 2.0
      signal having 6-fold hyperfine splitting (A = 95 G) typical of octahedrally
      coordinated Mn(II) in a protein. Quantitation of the EPR spin yields 3.4 +/- 0.3
      g-atoms of Mn(II) per holoenzyme. When exposed anaerobically to its natural
      substrate, 3,4-dihydroxyphenylacetate (3,4-DHPA), the EPR spectrum undergoes a
      dramatic change characterized by the attenuation of the g = 2 signal and the
      appearance of new signals at g = 1.2, 2.9, 4.3, and 16. The g = 4.3 signal
      displays 6-fold hyperfine splitting (A = 95 G) that unambiguously assigns it to
      the Mn(II) center. The appearance of these new signals indicates a large increase
      in zero-field splitting suggestive of a change in ligand coordination to the
      Mn(II) center. Similarly perturbed signals are seen in the EPR spectra of MndD
      complexed with the comparably active substrate analog, D,L-3,4
      dihydroxymandelate, or the tight-binding inhibitor, p-nitrocatechol, but not in
      the complexes with weaker binding substrates and inhibitors. The fact that only
      strong-binding substrates and inhibitors significantly perturb the Mn(II) EPR
      signal strongly suggests that the substrate coordinates to the Mn(II) center in
      the catalytic pathway.

PMID- 8555171
TI  - Temperature and pH dependences of hydrogen exchange and global stability for
      ovomucoid third domain.
AB  - Two-dimensional nuclear magnetic resonance spectroscopy has been used to monitor
      proton-deuterium exchange rates (kobs) for more than 30 residues in turkey
      ovomucoid third domain. To test whether exchange is governed by global unfolding,
      rates were measured over a wide range of pH and temperatures where the change in
      the free energy of unfolding (delta Gzerou) is known [Swint, L., & Robertson, A.
      D. (1993) Protein Sci. 2, 2037-2049; Swint-Kruse, L., & Robertson, A. D. (1995)
      Biochemistry 34, 4724-4732]. Under conditions where EX2 kinetics are observed, a
      subset of 6-11 residues exhibits a one-to-one correlation with global stability.
      These residues are all located in central regions of secondary structures. Many
      other sites show varied degrees of correlation with delta Gzerou, while some are
      slower than expected on the basis of delta Gzerou alone. Preliminary evidence
      suggests that the latter is due to deviation from EX2 kinetics, even though
      experimental conditions are relatively mild (pH* 3 and 40 degrees C) compared to
      those in which deviations were observed for bovine pancreatic trypsin inhibitor.
      These results, together with similar observations for hen egg white lysozyme and
      barnase, suggest that EX2 kinetics should not be assumed when interpreting
      exchange studies.

PMID- 8555172
TI  - Interactions contributing to the formation of a beta-hairpin-like structure in a
      small peptide.
AB  - A 12 amino acid peptide, model BB, was designed to adopt a beta-hairpin tertiary
      structure in water that might be stabilized by a variety of local, nonlocal,
      polar, and nonpolar interactions. The conformational properties of model BB with
      and without an intramolecular disulfide bond (BB-O and BB-R, respectively) were
      characterized by NMR and CD spectroscopy. The set of observed short- and medium
      range nOes were consistent with the formation of stable beta-hairpin-like
      structures by both BB-R and BB-O. BB-O adopts two distinct conformations that
      differ from each other in the designed reverse turn segment. A reasonably well
      defined set of structures was obtained by using restraints from the NMR data in
      distance geometry calculations. None of the beta-hairpin-like structures contain
      a beta-sheet hydrogen bonding network. The distinctive feature of intrastrand and
      cross-strand pairing of threonine residues observed in all of the calculated
      structures suggests that hydrophobic interactions between the gamma-methyl groups
      of threonine residues may be the structure-determining interaction in model BB.
      The implications of these results for the formation of beta-sheets during protein
      folding, the aggregation of peptides as beta-sheets, and the de novo design of
      independently folding beta-hairpin-like peptides are considered.

PMID- 8555173
TI  - Identification of a sequence of apolipoprotein A-I associated with the efflux of
      intracellular cholesterol to human serum and apolipoprotein A-I containing
      particles.
AB  - The effect of monoclonal antibodies against apolipoprotein A-I (apoA-I) on the
      efflux of intracellular and plasma membrane cholesterol from HepG2 cells to human
      serum, high-density lipoprotein (HDL), apoA-I, and apoA-I/phosphatidylcholine
      complex (apoA-I/PC) was studied. Fab fragments of two monoclonal antibodies, AI-3
      (residues 140-147) and Al-4.2 (residues 149-150), inhibited the efflux of
      intracellular cholesterol to serum in a dose-dependent manner. In combination,
      these antibodies were twice as effective than when used alone. None of the
      antibodies tested inhibited efflux of the plasma membrane cholesterol. When
      different types of acceptors were compared for their ability to promote
      intracellular cholesterol efflux, they were effective in the following order:
      serum > HDL > apoA-I/PC > pure apoA-I. Antibody AI-3 inhibited efflux of
      intracellular cholesterol to serum, HDL, and pure apoA-I, but not to apoA-I/PC.
      Antibody AI-4.2 inhibited efflux to serum, apoA-I/PC, and pure apoA-I, but not to
      HDL. An explanation for this is that antibody AI-4.2 reacts poorly with isolated
      alpha-HDL in an immunoprecipitation assay and has higher affinity for pre beta 2
      HDL and pre beta 3-HDL particles than antibody AI-3 in nondenaturing two
      dimensional electrophoresis. In conclusion, we have demonstrated that a region of
      apoA-I within or adjacent to residues 140-150 determines the ability of apoA-I to
      promote intracellular cholesterol efflux.

PMID- 8555174
TI  - Isolation of a tripeptide from a random phage peptide library that inhibits P1,P4
      diadenosine 5'-tetraphosphate binding to its receptor.
AB  - Extracellular P1,P4-diadenosine 5'-tetraphosphate (Ap4A) has been implicated as a
      modulator of cell stress. We have previously demonstrated specific receptors for
      Ap4A at the surface of cardiac myocytes (Walker et al., 1993a). In addition, we
      have isolated a monoclonal antibody (mAb TL4) that recognized the Ap4A receptor
      and inhibited binding of Ap4A to its receptor (Walker & Hilderman, 1993). As part
      of our effort to characterize the Ap4A receptor building domain, we screened a
      random phage peptide library with mAb TL4. After affinity purification of
      specifically bound phage, we isolated 38 individual phage clones. Twenty-eight of
      these clones bound mAb TL4 in ELISA and dot blot analyses. Twenty-two of the
      twenty-eight individual clones contained inserts with an RGS tripeptide sequence.
      Synthetic RGS peptide specifically inhibits the binding of mAb TL4 to its
      membrane receptor. Furthermore, the RGS peptide also inhibits [3H]Ap4A binding to
      its receptor. These data are consistent with the RGS peptide mimicking part of
      the mAb TL4 recognition site on the Ap4A receptor. The The RGS peptide may be
      used to help characterize the Ap4A receptor binding domain and to help determine
      the physiological significance of the interaction between Ap4A and its receptor.

PMID- 8555175
TI  - Application of immobilized metal ion chelate complexes as pseudocation exchange
      adsorbents for protein separation.
AB  - The interactions of horse muscle myoglobin (MYO), tuna heart cytochrome c (CYT),
      and hen egg white lysozyme (LYS) with three different immobilized metal ion
      affinity (IMAC) adsorbents involving the chelated complexes of the hard Lewis
      metal ions Al3+, Ca2+, Fe3+, and Yb3+ and the borderline Lewis metal ion Cu2+
      have been investigated in the presence of low- and high-ionic strength buffers
      and at two different pH values. In contrast to the selectivity behavior noted
      with buffers of high ionic strength, with low-ionic strength buffers, these three
      proteins interact with the hard metal ion IMAC adsorbents in a manner more
      characteristic of cation exchange behavior, although in contrast to the cation
      exchange chromatography of these proteins, as the pH value of the elution buffer
      was increased, the retention also increased. The selectivity differences observed
      under these conditions appear to be due to the formation of hydrolytic complexes
      of these immobilized metal ion chelate systems involving a change in the
      coordination geometry of the im-M(n+)-chelate at higher pH values. The
      experimental observations have been evaluated in terms of the effective charge on
      the immobilized metal ion chelate complex and the charge characteristics of the
      specific proteins.

PMID- 8555176
TI  - Properties of the selenium- and molybdenum-containing nicotinic acid hydroxylase
      from Clostridium barkeri.
AB  - NADP(+)-coupled nicotinic acid hydroxylase (NAH) has been purified to near
      homogeneity from Clostridium barkeri by an improved purification scheme that
      allowed the isolation of milligram amounts of enzyme of higher specific activity
      then previously reported. NAH is most stable at alkaline pH in the presence of
      glycerol. The protein which consists of four dissimilar subunits occurs in forms
      of different molecular masses. There are 5-7 Fe, 1 FAD, and 1 Mo per 160 kDa
      protein promoter. Mo in the enzyme is bound to a dinucleotide form of
      molybdopterin and is coordinated with selenium. Mo(V), flavin radical, and two
      Fe2S2 clusters could be observed with EPR spectroscopy. The Se cofactor which is
      essential for nicotinic acid hydroxylase activity could be released from NAH as a
      reactive low molecular weight compound by a number of denaturing procedures.
      Parallel losses of Se and catalytic activity were observed during purification
      and storage of the enzyme. Addition of sodium selenide or selenophosphate did not
      restore the catalytic activity of the enzyme. Instead, NAH is reversibly
      inactivated by these compounds and also by sulfide. Cyanide, a common inhibitor
      of Mo-containing hydroxylases, does not affect NAH catalytic activity. The "as
      isolated" enzyme exhibits a Mo(V) EPR signal (2.067 signal) that was detected at
      early stages of purification. NAH exhibits a high substrate specificity toward
      electron donor substrates. The ability of a nicotinate analog to reduce NAH
      (disappearance of 2.067 signal) correlates with the rate of oxidation of the
      analog in the standard assay mixture. The properties of NAH differentiate the
      enzyme from known Mo-containing hydroxylases.

PMID- 8555177
TI  - The mechanism of binding staphylococcal protein A to immunoglobin G does not
      involve helix unwinding.
AB  - Structural changes in staphylococcal protein A (SpA) upon its binding to the
      constant region (Fc) of immunoglobulin G (IgG) have been studied by nuclear
      magnetic resonance and circular dichroism (CD) spectroscopy. The NMR solution
      structure of the engineered IgG-binding domain of SpA, the Z domain (an analogue
      of the B domain of SpA), has been determined by simulated annealing with
      molecular dynamics, using 599 distance and dihedral angle constraints. Domain Z
      contains three alpha-helices in the polypeptide segments Lys7 to His18 (helix 1),
      Glu25 to Asp36 (helix 2), and Ser41 to Ala54 (helix 3). The overall chain fold is
      an antiparallel three-helical bundle. This is in contrast to the previously
      determined X-ray structure of the similar SpA domain B in complex with Fc, where
      helix 3 is not observed in the electron density map [Deisenhofer, J. (1981)
      Biochemistry 20, 2361-2370], but similar to the solution NMR structure of domain
      B, which is also a three-helical bundle structure [Gouda, H., et al. (1992)
      Biochemistry 31, 9665-9672]. In order to characterize possible secondary
      structural changes associated with IgG binding, far-UV CD spectra were collected
      for the Z domain, an engineered repeat of this molecule (ZZ), recombinant Fc from
      IgG subclass 1 (Fc1), recombinant Fc from IgG subclass 3 (Fc3), and mixtures of
      Z/Fc1, Z/Fc3, ZZ/Fc1, and ZZ/Fc3. Fc3 was included as a control for possible
      changes of the CD spectrum in the mixture of noncomplexed molecules, since SpA is
      known not to bind Fc3. From these CD spectra, it was concluded that the third
      alpha-helix in Z is not disrupted in its complexes with Fc1. Similar results were
      obtained for the ZZ molecule. However, in both Z and ZZ there are some
      perturbations in CD spectra at high energy wavelengths (i.e., lambda < 215 nm)
      accompanying complex formation. On the basis of the combined CD and NMR results,
      as well as previously described binding studies of Z mutant proteins to Fc1, we
      conclude that the Z domain maintains its three-helical bundle structure in the Z
      Fc complex, though there may be a small structural change involved in the binding
      mechanism.

PMID- 8555178
TI  - Activation of myosin light chain kinase and nitric oxide synthase activities by
      engineered calmodulins with duplicated or exchanged EF hand pairs.
AB  - We have constructed three engineered calmodulins (CaMs) in which the two EF hand
      pairs have been substituted for one another or exchanged: CaMNN, the C-terminal
      EF hand pair (residues 82-148) has been replaced by a duplication of the N
      terminal pair (residues 9-75); CaMCC, the N-terminal pair has been replaced by a
      duplication of the C-terminal pair; CaMCN, the two EF had pairs have been
      exchanged. Skeletal muscle myosin light chain kinase (skMLCK) activity is
      activated to 75% of the maximum level by CaMCC and to 45% of the maximum level by
      CaMCN and is not significantly activated by CaMNN; Kact or Ki values for the
      engineered CaMs are 2-3.5 nM. Smooth muscle myosin light chain kinase activity
      (gMLCK) is fully activated by CaMCN and is not significantly activated by either
      CaMNN or CaMCC; the Kact value for CaMCN is 2 nM and the Ki values for CaMNN and
      CaMCC are 10 and 40 nM, respectively. Cerebellar nitric oxide synthase activity
      (nNOS) is fully activated by CaMNN and CaMCN and is not significantly activated
      by CaMCC; the engineered CaMs have Kact or Ki values for this enzyme activity of
      2-8 nM. These results indicate that the EF hand pairs contain distinct but
      overlapping sets of determinants for binding and activation of enzymes, with the
      greater degree of overlap in determinants for binding. Furthermore, while the
      structural changes associated with swapping the EF hand pairs do not affect
      activation of nNOS or gMLCK activities, they significantly reduce activation of
      skMLCK activity, indicating that this process requires specific determinants in
      CaM outside the EF hand pairs.

PMID- 8555179
TI  - Conformational order of phospholipids incorporated into human erythrocytes: an
      FTIR spectroscopy study.
AB  - Acyl chain perdeuterated dimyristoylphosphatidylcholine (DMPC-d54) and
      dimyristoylphosphatidylserine (DMPS-d54) were incorporated by incubation into
      human erythrocytes. Light microscopic analysis demonstrated that erythrocytes
      incubated with DMPC-d54 became echinocytic while those incubated with DMPS-d54
      became stomatocytic. This indicates that DMPC-d54 was incorporated preferentially
      into the outer monolayer whereas DMPS-d54 was selectively incorporated into the
      inner monolayer. Fourier transform infrared (FTIR) spectroscopy was used to
      monitor the conformational order of the incorporated phospholipids. The
      asymmetric CD2 stretching frequency of the inserted perdeuterated acyl chains was
      measured in both isolated membranes and intact erythrocytes as a function of
      temperature. DMPC-d54 incorporated into erythrocytes exhibited a cooperative
      phase transition at approximately 19 degrees C, i.e., at the same temperature as
      pure vesicles. In contrast, DMPS-d54 incorporated into red cells exhibited no
      phase transition, but possessed conformational order similar to that of the
      liquid-crystalline state. These results suggest that DMPC-d54 persists in domains
      in the outer monolayer while DMPS-d54 is dispersed in the inner monolayer. These
      experiments are the first to demonstrate that FTIR spectroscopy can be utilized
      to monitor directly a specific species of lipid molecule from the entire
      phospholipid population.

PMID- 8555180
TI  - Importance of the region around glycine-338 for the activity of enzyme I of the
      Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system.
AB  - The gene encoding enzyme I of the phosphoenolpyruvate:sugar phosphotransferase
      system from an Escherichia coli enzyme I mutant was cloned and sequenced. The
      mutation was shown to be a guanine to adenine transition resulting in an altered
      protein in which glycine-338 was replaced by aspartic acid. The enzyme I
      structural gene was mutated to change glycine-338 to a variety of other amino
      acid residues. Fermentation tests indicated that glycine-338 could be mutated to
      alanine with no gross loss in phosphotransferase activity, while mutation to
      valine, glutamic acid, aspartic acid, arginine, histidine, or asparagine led to
      significant loss of activity. An expression vector for enzyme I was mutated to
      change glycine-338 to a variety of other amino acid residues and highly purified
      mutant proteins were prepared. Analysis of phosphorylation of the proteins by PEP
      indicated that mutation of glycine-338 to alanine had little effect on
      phosphorylation, mutation to valine substantially decreased phosphorylation,
      change to histidine or arginine drastically diminished phosphorylation, and
      mutation to aspartic or glutamic acids abolished phosphorylation activity.
      Mutation at glycine-338 influences the autophosphorylation rather than the
      phosphoryl transfer activity of enzyme I.

PMID- 8555181
TI  - Discodermolide, a cytotoxic marine agent that stabilizes microtubules more
      potently than taxol.
AB  - Computer-assisted structure analysis indicated (+)-discodermolide, a
      polyhydroxylated alkatetraene lactone marine natural product, was an antimitotic
      compound, and we confirmed this prediction. Previous work had shown an
      accumulation of discodermolide-treated cells in the G2/M portion of the cell
      cycle, and we have now found that discodermolide arrests Burkitt lymphoma cells
      in mitosis. Discodermolide-treated breast carcinoma cells displayed spectacular
      rearrangement of the microtubule cytoskeleton, including extensive microtubule
      bundling. Microtubule rearrangement that occurred with 10 nM discodermolide
      required 1 microM taxol. Discodermolide had equally impressive effects on tubulin
      assembly in vitro. Near-total polymerization occurred at 0 degree C with tubulin
      plus microtubule-associated proteins (MAPs) under conditions in which taxol at an
      identical concentration was inactive. Without MAPs and/or without GTP, tubulin
      assembly was also more vigorous with discodermolide than with taxol under every
      reaction condition examined. Discodermolide-induced polymer differed from taxol
      induced polymer in that it was completely stable at 0 degree C in the presence of
      high concentrations of Ca2+. In a quantitative assay designed to select for
      agents more effective than taxol in inducing assembly, discodermolide had an EC50
      value of 3.2 microM versus 23 microM for taxol.

PMID- 8555182
TI  - Interactions between mutant and wild-type band 3 subunits in hereditary Southeast
      Asian ovalocytic red blood cell membranes.
AB  - Red cell membranes from individuals with Southeast Asian ovalocytosis (SAO)
      contain approximately equal proportions of wild-type band 3 and a mutant SAO band
      3 which lacks residues 400-408. It is known that the Vmax for anion exchange in
      SAO cells is reduced by about 50%, that SAO band 3 does not transport anions when
      expressed alone in a cellular expression system, that SAO band 3 does not bind
      stilbenedisulfonates, and that about 50% of the band 3 exists as wild-type/SAO
      heterodimers. In this report, we show that the kinetics of H2DIDS (4,4'
      diisothiocyanatodihydro-2,2'-stilbenedisulfonate) release from the wild-type band
      3 in SAO membranes is biphasic. The two phases were present in about equal
      proportions, with rate constants differing by about 5-fold. In contrast; control
      cells showed monophasic, exponential kinetics with a rate constant comparable to
      that of the fast phase of SAO membranes. We assign the fast phase in SAO
      membranes to H2DIDS release from wild-type subunits within homodimers and the
      slow phase to H2DIDS release from the wild-type subunit within the heterodimer.
      No differences were observed in kinetic studies of H2DIDS binding. These results
      suggest that the mutant band 3 subunit alters the conformation of its neighboring
      wild-type subunit within the heterodimer, resulting in about a 4-fold higher
      H2DIDS affinity. Additional evidence suggesting that the interactions in the
      heterodimer may be confined to a region of the wild-type subunit containing the C
      terminal subdomain is presented. The relationship of these subunit interactions
      to the observation of a reduced cellular anion transport function is discussed.

PMID- 8555183
TI  - Cross-link between cys 374 and cys 10 of actin abolishes polymerizability and
      allows study of the properties of the "F-actin monomer".
AB  - Actin cross-linked between cys 374 and cys 10 via a disulfide-containing bridge,
      c-A, is completely unpolymerizable even in the presence of phalloidin. Upon the
      addition of dithiothreitol, c-A polymerizes with high yield, indicating that
      denaturation due to the modification was almost absent. In the present study we
      show that cross-linked actin is a useful model for studying the properties of
      monomeric actin under polymerization conditions. Addition of salt, for example,
      produced fluorescence changes possibly reflecting conformational transitions but
      did not lead to the development of phalloidin binding capacity. Cross-linking of
      the two cysteine residues also caused a decrease in the nucleotide exchange rate
      by a factor of ca. 3, an effect that was fully reversed by the addition of KCl.
      Cross-linked actin inhibits DNase I to the same extent as G-actin and binds
      thymosin beta 4 and profilin as shown by cross-linking studies. Capping capacity
      for the barbed end of the filament was not observed, although it might have been
      expected from the fact that both ends of the cross-link are anchored to subdomain
      1. Using the 61-FITC derivative of c-A we showed that c-A is able to bind to
      myosin S1 with a KD in the microM range. In agreement with this, c-A shows
      actomyosin ATPase activity with a Kapp comparable to that of F-actin, but a Vmax
      decreased by a factor of ca. 11. The c-A myosin S1 complex provides the hitherto
      smallest model of actomyosin, which appears promising for crystallization and X
      ray analysis.

PMID- 8555184
TI  - Inhibitory properties of a novel human Kunitz-type protease inhibitor homologous
      to tissue factor pathway inhibitor.
AB  - In a previous report, we described the molecular cloning, expression, and partial
      characterization of a second human tissue factor pathway inhibitor (TFPI), which
      we designated as TFPI-2 [Sprecher, C. A., et al. (1994) Proc. Natl. Acad. Sci.
      U.S.A. 91, 3353-3357]. Recombinant TFPI-2 inhibited the amidolytic activity of
      trypsin as well as that of factor VIIa in complex with tissue factor. TFPI-2
      recently has been shown to be identical to placental protein 5 (PP5), a
      glycoprotein originally isolated from placenta that exhibits serine protease
      inhibitory activity. In the present study, we have examined TFPI-2/PP5 for its
      ability to inhibit a number of serine proteases involved in blood coagulation and
      fibrinolysis, inasmuch as TFPI-2/PP5 prolonged the coagulation time of human
      plasma induced by either tissue factor or contact activation in a dose-dependent
      manner. In addition to its ability to inhibit the amidolytic and proteolytic
      activities of the factor VIIa-tissue factor complex, TFPI-2/PP5 strongly
      inhibited the amidolytic activities of human factor XIa, human plasma kallikrein,
      and human plasmin with Ki values of 15, 25, and 3 nM, respectively. TFPI-2/PP5
      was also a weak inhibitor of the activation of factor X by a complex of human
      factor IXa and poly(lysine) with an apparent Ki of 410 nM. Heparin markedly
      enhanced the ability of TFPI-2/PP5 to inhibit factor VIIa-tissue factor both in
      the solution phase and on cell surfaces. In addition, heparin augmented the
      inhibition of human factor Xa amidolytic activity at relatively high levels (10
      100 nM) of TFPI-2/PP5. No significant inhibition of glandular kallikrein, urinary
      plasminogen activator, tissue plasminogen activator, human activated protein C,
      human factor Xa, human thrombin, or leukocyte elastase was observed when these
      proteases were incubated with TFPI-2 in the absence of heparin.

PMID- 8555185
TI  - Folding topologies of human interleukin-6 and its mutants as studied by NMR
      spectroscopy.
AB  - To understand the structure-function relationship in the human interleukin-6 (IL
      6) system, comparative studies were performed on the basis of NMR data obtained
      using the wild-type IL-6 and six mutants. In each of the six mutants, either
      Leu152, Leu159, Leu166, Leu168, Leu175, or Leu182, which exist in the C-terminal
      receptor-binding region, was substituted with Val. The resonance assignments of
      Val, Ile, Leu, and Phe residues were made by using specific double-labeling and
      site-specific mutagenesis strategies. On the basis of chemical shift and NOE data
      collected for six IL-6 mutants and those for the wild-type IL-6, we analyzed the
      structural changes induced by the substitution of each of the six Leu residues.
      The NMR data showed that substitution of Leu182 with Val (L182V) induced no
      structural change in IL-6, suggesting that Leu182 is located on the surface of
      the IL-6 molecule. A significant decrease in receptor-binding activity was
      observed in the L182V mutant. It was concluded that the side chain of Leu182 is
      directly involved in receptor binding. Substitution of Leu175 with Val (L175V)
      was shown to induce a significant structural change in IL-6. The NMR data are
      discussed on the basis of the location of four helix elements and an up-up-down
      down helix topology of the predicted structure of IL-6 [Bazan, J.F. (1991) Neuron
      7, 197-208]. It is possible that helix D bent more sharply toward helix B in the
      L175V mutant than in the wild-type IL-6 to maintain a closely packed and solvent
      inaccessible core formed in the mutated region. It is suggested that the kink of
      helix D is related to the decrease in receptor-binding activity in the L175V
      mutant. On the basis of the observed NOE network, the folding topology of IL-6
      was analyzed. A comparison of the folding topology of IL-6 with that of human
      granulocyte colony-stimulating factor determined by X-ray crystallography [Hill,
      C. P., Osslund, T. D., & Eisenberg, D. (1993) Proc. Natl. Acad. Sci. U.S.A. 90,
      5167-5171] indicated that IL-6 has a significant similarity of folding topology
      to that of human granulocyte colony-stimulating factor.

PMID- 8555186
TI  - Active site mutation of the C3-like ADP-ribosyltransferase from Clostridium
      limosum--analysis of glutamic acid 174.
AB  - Clostridium limosum ADP-ribosyltransferase modifies low molecular mass GTP
      binding proteins of the Rho subtype family. Here we cloned and sequenced the gene
      of the transferase and expressed it in Escherichia coli. The gene encodes a
      protein of 250 amino acids (M(r) = 27,840), with a putative signal peptide of 45
      amino acids, that shows about 60-65% identity with C3 transferases from
      Clostridium botulinum. The mature C. limosum transferase was expressed as a
      maltose-binding fusion protein in E. coli and purified to apparent homogeneity.
      To study the functional role of Glu174 of C. limosum transferase, which was
      recently photoaffinity-labeled with [carbonyl-14C]NAD [Jung, M., et al. (1993) J.
      Biol. Chem. 268, 23215-23218], two mutants E174D and E174Q were constructed by a
      polymerase chain reaction-based system. The E174D and E174Q mutants showed a
      dramatic decrease in kcat, but no major changes in Km,NAD. Furthermore,
      replacement of Glu174 by aspartic acid and glutamine largely reduced and
      completely blocked UV-induced incorporation of [carbonyl-14C]NAD into the
      transferase. The data indicate that Glu174 is an active site residue of C.
      limosum transferase.

PMID- 8555187
TI  - Cyclic AMP-dependent phosphoprotein components I and II interact with beta gamma
      subunits of transducin in frog rod outer segments.
AB  - Components I and II (CI&II) in frog rod outer segments (ROS) are prominent cAMP
      dependent protein kinase (PK-A) substrates. Their phosphorylation level is high
      in the dark, and illumination causes dephosphorylation. In order to understand
      their physiological role in phototransduction, biochemical characterization of
      CI&II phosphorylation was performed. Fractionation of phosphorylated ROS proteins
      showed that CI&II in the soluble fraction were highly phosphorylated by
      endogenous PK-A, whereas those in the membrane-associated protein fractions were
      not. The latter proteins could be phosphorylated by purified catalytic subunit of
      PK-A (PK-Acat) while the former proteins were not, suggesting that membrane-bound
      CI&II are normally much less phosphorylated. Treatments that dissociate the alpha
      subunit (alpha t) of transducin (Gt) from beta gamma subunits (beta gamma t) and
      thus produce excess free subunits of Gt in the soluble fraction caused inhibition
      of CI&II phosphorylation in the soluble fraction and enhancement of CI&II
      phosphorylation in the peripheral membrane fractions containing less Gt.
      Unphosphorylated CI&II tightly associated with the washed ROS membranes could be
      extracted after phosphorylation by PK-Acat. Phosphorylation also caused elution
      of beta gamma t from the membrane under the same conditions. Cross-linking by the
      maleimidobenzoyl-N-hydroxysuccinimide ester of the peripheral membrane fraction
      produced a distinct phosphorylated 50 kDa product with concurrent disappearance
      of the beta subunit of transducin (beta t) and phosphorylated CI&II. This
      phosphorylated cross-linked product was not recognized by a monoclonal anti-alpha
      t antibody but was recognized by antiserum against beta t, suggesting that the 50
      kDa protein is a complex of beta gamma t and CI&II. Amino terminal sequencing of
      components I and II suggests that they are identical proteins with a unique
      sequence unrelated to other proteins in protein data bases. Phosphopeptide
      mapping of phosphorylated CI&II in the soluble fraction yielded two trypsinized
      phosphopeptides, while that in the peripheral membrane fractions showed only one
      phosphopeptide. These data suggest that multiple phosphorylation of CI&II alters
      their cellular localization. We conclude that phosphorylation of CI&II controls
      their localization in frog ROS and an interaction of CI&II with subunits of Gt
      regulates their phosphorylation.

PMID- 8555188
TI  - Intermembrane molecular contacts by polymyxin B mediate exchange of
      phospholipids.
AB  - Direct intermembrane exchange of dimyristoylphosphatidylmethanol is mediated by
      polymyxin B (PxB), a cationic amphipathic cyclic decapeptide. The possibility
      that the phospholipid exchange is mediated by solubilization of phospholipids or
      by fusion of vesicles is ruled out. By kinetic and spectroscopic methods it is
      shown that the exchange occurs directly through vesicle-vesicle contacts formed
      by a few PxB molecules. The contact is stable on the time scale of several
      minutes such that neither PxB nor the vesicles in the pair forming a contact
      exchange with excess vesicles. Several contacts may be formed on a vesicle, which
      leads to the formation of a cluster of vesicles, and the lipid molecules on the
      outer monolayers of vesicles exchange throughout the cluster. Kinetics of
      substrate replenishment during processive interfacial catalysis suggests that the
      exchange of anionic lipids over the contact occurs at a rate considerably faster
      than 300 s-1. The exchange through the contact is specific for certain lipids,
      and phospholipids with a modified head group or phospholipase A2 bound to a
      vesicle are not transferred to the other vesicle in contact. Since this
      phenomenon has not been described before, possible implications of direct vesicle
      vesicle exchange of phospholipids through peptide-mediated molecular contacts are
      discussed. Such a mechanism for intermembrane transfer of phospholipids could be
      responsible for intracellular trafficking and sorting of phospholipids; it could
      be a necessary first step for the sequence of events leading to budding,
      vesiculation, and secretion; and PxB-mediated transfer between the inner and
      outer membranes of Gram-negative bacteria could also account for its antibiotic
      action.

PMID- 8555189
TI  - Interaction of transforming growth factor beta receptors with apolipoprotein
      J/clusterin.
AB  - Proteins mediating the transmission of the signal from an activated transforming
      growth factor beta (TGF beta) receptor complex have not been identified. Using a
      yeast interaction screen to search for proteins that associate with the type II
      TGF beta receptor (RII), we isolated a protein which was identical to
      apolipoprotein J (apoJ)/clusterin. ApoJ interacts with both the type I (RI) and
      type II (RII) TGF beta receptors but does not interact with the epidermal growth
      factor (EGF) receptor. The interaction between RII and apoJ occurs through the C
      terminal 127 amino acids of RII. Deletion of this region, which contains the
      kinase insert 2 domain, abrogates binding to apoJ. The binding of apoJ to either
      the RI and the RII receptors is direct, not requiring other proteins, and is not
      specific for the alpha or beta subunit of apoJ since both subunits are effective
      in competing for binding. RI and RII fusion proteins are capable of precipitating
      the 60 kDa intracellular form of apoJ from [35S]methionine-labeled cellular
      lysates, suggesting that this form of the protein may play some role in TGF beta
      signaling or TGF beta receptor processing.

PMID- 8555190
TI  - Hydrolysis of dihydrouridine and related compounds.
AB  - Dihydrouridine is absent from the tRNA of almost all hyperthermophiles and most
      Archaea but is ubiquitous in the tRNA of Eubacteria and Eukaryotes. In order to
      investigate whether this could be due to instability, the rate of ring opening of
      dihydrouridine was measured between 25 and 120 degrees C. The dihydrouridine ring
      is stable at 25 degrees C, but the half-life at 100 degrees C and pH 7 is 9.1 h,
      which is comparable to the doubling time of hyperthermophiles. This suggests an
      explanation for the absence of dihydrouridine from the tRNA of hyperthermophiles.
      The rates of ring opening of dihydrouracil, dihydrothymine, and 1-N
      methyldihydrouracil were measured at 100 degrees C and pH 6-9, as were the
      equilibrium constants for ring closure of the ureido acids to the dihydrouracils.
      The pH rate profiles for ring opening and ring closing were calculated from the
      data. Possible roles for dihydrouracils in the pre-RNA world are discussed.

PMID- 8555191
TI  - Escherichia coli tryptophanyl-tRNA synthetase mutants selected for tryptophan
      auxotrophy implicate the dimer interface in optimizing amino acid binding.
AB  - Tryptophan auxotrophs of Escherichia coli in which mutations were mapped to the
      trpS locus (encoding tryptophanyl-tRNA synthetase) have been previously isolated.
      We have investigated the tryptophanyl-tRNA synthetase (TrpRS) purified from six
      auxotrophic strains for changes in amino acid activation and aminoacylation.
      Steady-state kinetic analyses show that these mutant TrpRS proteins have
      increases in the apparent KM for tryptophan, decreases in turnover number, or
      both, without significant changes in the apparent KM for ATP or tRNA(Trp). The
      crystal structure of a highly homologous tryptophanyl-tRNA synthetase from
      Bacillus stearothermophilus in a complex with the cognate aminoacyl adenylate
      allowed us to place the mutations in a structural context. The mutations in the
      enzymes are located in the KMSKS loop (M196I), in or near the active site (D112E,
      P129S, A133E) or far from the active site. The last three mutants (T60R, L91F,
      G329S) could not be predicted by examination of the protein structure as they
      line an interface between the C-terminal alpha-helix of one subunit and the
      Rossmann folds of both subunits, thus affecting a specific region of the dimer
      interface. These results support a role for dimerization in properly configuring
      the two active sites of the dimeric enzymes in the Trp/Tyr subclass of class I
      aminoacyl-tRNA synthetases in order to achieve optimal catalysis.

PMID- 8555192
TI  - Torsional dynamics and orientation of DNA--DAPI complexes.
AB  - The flexibility of calf thymus DNA and several polynucleotides was measured using
      the anisotropy decay of DAPI bound to DNA, a minor groove probe. DNA torsional
      dynamics were analyzed using the Schurr model [Allison, S. A., & Schurr, J. M.
      (1979) Chem. Phys. 41, 35-44] in the infinite polymer length approximation. Time
      resolved fluorescence depolarization was measured using a frequency-double mode
      locked dye laser and frequency-domain acquisition methods. At very high P/D
      ratios, the anisotropy decay is dominated by DNA torsional dynamics. The
      recovered values of the torsional elastic constant were in good agreement with
      literature values obtained using other DNA probes. The exact knowledge of the
      angle between the probe emission dipole transition moment and the helix axis is
      critical for the determination of the polymer elastic constant. At low P/D
      ratios, energy transfer between dye molecules strongly contributes to the
      anisotropy decay. We have developed a statistical model that describes the
      anisotropy decay, when the correct geometrical factors are included. At low P/D
      ratios the anisotropy decay is dominated by fluorescence homotransfer. In this
      regime, it is possible to determine the orientation of the dye molecule with
      respect to the polymer with accuracy. The values obtained for the distance and
      orientation of the DAPI molecules in solution using the fluorescence measurements
      are in excellent agreement with those from the crystal structure of the
      oligonucleotides-DAPI complex by Dickerson's group [Larsen T.A., Goodsell, D. S.,
      Cascio, D., Grzeskowiak, K., & Dickerson, R. E. (1989) J. Biomol. Struct. Dyn. 7,
      477-491].

PMID- 8555193
TI  - Simulations of chaperone-assisted folding.
AB  - We investigated a chaperone mechanism of protein folding using a 36-mer model on
      a cubic lattice. The mechanism simulates folding, which proceeds with repetitive
      cycles of binding, unfolding, and releasing of misfolded metastable states. We
      measured the yield enhancement due to this mechanism for sequences selected by
      evolutionary design and showed that the binding and releasing mechanism is
      efficient for the yield enhancement of folding for sequences that are poorly
      designed, i.e., where selection is not adequately strong. From this it follows
      that the chaperone mechanism can be considered as the evolutionary alternative to
      compensate for poor sequence design. On the other hand, random sequences show a
      decrease in yield and no effect on the total mean first passage time when the
      proposed chaperone mechanism is implemented, thus implying that sequence
      optimization is a necessary condition for the efficiency of the proposed
      mechanism. We qualitatively reproduced experimental results for folding in the
      presence of GroEL/GroES, fit our results with the aid of a double-exponential
      model of folding kinetics, and characterized the conditions under which this
      mechanism of chaperone action affects folding.

PMID- 8555194
TI  - Direct binding of ethanol to bovine serum albumin: a fluorescent and 13C NMR
      multiplet relaxation study.
AB  - Molecular mechanisms of ethanol interaction with proteins are not well
      understood. In the present study, direct interaction of ethanol with hydrophobic
      binding sites on fatty acid free bovine serum albumin (BSA) was determined using
      the fluorescent probe 1-anilinonaphthalene-8-sulfonic acid (1,8-ANS), cis
      parinaric acid, and 13C NMR. The affinity of ethanol for BSA (Kd) was (5.21 +/-
      0.31) x 10(-2) mol. Ethanol (25-200 mmol) competitively inhibited 1,8-ANS binding
      to BSA in a concentration-dependent manner with a Ki (concentration of ethanol
      that decreased 1,8-ANS binding by 50%) of 658 mmol. Preincubation of BSA with
      ethanol significantly decreased cis-parinaric acid binding to BSA, indicating
      interaction of ethanol with hydrophobic fatty acid-binding site(s) on BSA.
      Furthermore, ethanol was found to act on three of the five fatty acid-binding
      sites on BSA. These data indicated selectivity in the interaction of ethanol with
      hydrophobic sites on BSA. 13C NMR multiplet relaxation was used to characterize
      the interaction of ethanol with binding sites on BSA. Detailed analysis of
      [13C]ethanol relaxation data obtained in the presence of increasing BSA
      concentrations (25-200 mg/mL) led to the conclusion that the ethanol methyl
      group, as opposed to its hydroxyl group, binds in a hydrophobic pocket(s) on the
      protein. Ethanol-induced changes in activity of certain proteins may result from
      direct binding of ethanol to specific hydrophobic binding sites and/or
      displacement of endogenous ligands from those sites.

PMID- 8555195
TI  - EPR polarization studies on Mn catalase from Lactobacillus plantarum.
AB  - The binuclear manganese active site of Mn catalase catalyzes redox
      disproportionation of hydrogen peroxide, forming dioxygen and water. We report
      here multifrequency EPR and microwave polarization studies of the catalytically
      active homovalent Mn2+ complex of Lactobacillus plantarum Mn catalase, resolving
      spectra from each of the thermally accessible multiplet states of the coupled
      complex by multivariate methods. The experimental spectra have been simulated
      using computational approaches for the binuclear cluster to predict both
      intensity and polarization for arbitrary values of the ground state parameters.
      These two spectroscopic properties define the nature of the ground state
      wavefunctions and so serve as a sensitive and quantitative measure of the inter
      ion interactions in the reduced complex. Interpretation of the spectra in terms
      of a pair Hamiltonian that includes Heisenberg exchange, dipolar, single site
      zero field splitting, and Zeeman perturbations leads to the most complete ground
      state description of the active site metal centers. The results of this
      spectroscopic analysis support a picture of two high spin ions weakly coupled by
      exchange interactions (J = 40 cm-1) with relatively small dipole-dipole coupling
      and single site zero field splittings for the ligand-free reduced enzyme. The
      coupling between fluoride binding and protonation of the complex has been
      demonstrated by proton uptake studies. The binding of two fluoride ions in the
      active site dramatically changes the pair spectra, reflecting a substantially
      reduced J-coupling (J = 10.5 cm-1) that must be a consequence of perturbation of
      the bridging ligands. Anion binding to the binuclear Mn complex appears to result
      in poisoning of the active site by protons, possibly associated with insertion of
      fluoride into bridging positions of the dimanganese core.

PMID- 8555196
TI  - Mechanism of the reaction catalyzed by acetoacetate decarboxylase. Importance of
      lysine 116 in determining the pKa of active-site lysine 115.
AB  - Acetoacetate decarboxylase from Clostridium acetobutylicum (AAD) catalyzes the
      decarboxylation of acetoacetate via a Schiff base intermediate [Hamilton, G. A.,
      & Westheimer, F. H. (1959) J. Am. Chem. Soc. 81, 6332; Fridovich, I., &
      Westheimer F. H. (1962) J. Am. Chem. Soc. 84, 3208]. The pKa of the active-site
      lysine (Lys 115) is 6.0, 4.5 pKa units less than the pKa of lysine in solution
      [Kokesh, F. C., & Westheimer, F. H. (1971) J. Am. Chem. Soc. 93, 7270; Frey, P.
      A., Kokesh, F. C., & Westheimer, F. H. (1971) J. Am. Chem. Soc. 93, 7266;
      Schmidt, D. E., Jr., & Westheimer, F. H. (1971) Biochemistry 10, 1249].
      Westheimer and co-workers hypothesized that the pKa of Lys 115 is decreased by
      its spatial proximity to the epsilon-ammonium group of Lys 116. We have
      investigated this proposal by studying site-directed mutants of Lys 115 and Lys
      116. Two substitutions for Lys 115 (K115C and K115Q) were both catalytically
      inactive at pH 5.95, the pH optimum of wild type AAD, demonstrating the
      importance of this residue in catalysis. Activity could be restored to K115C by
      aminoethylation with 2-bromoethyl-ammonium bromide (2-BEAB). Substitutions for
      Lys 116 (K116C, K116N, and K116R) had reduced but significant activities at pH
      5.95. The effects of Lys 116 on the pKa of Lys 115 in the mutant AADs were
      evaluated following imine formation with 5-nitrosalicylaldehyde and reduction
      with NaBH4. Whereas the pKa of Lys 115 in K116R is similar to that observed for
      wild type AAD, the pKaS of Lys 115 in K116C and K116N were elevated to > 9.2.
      Alkylation of Cys 116 in K116C with 2-BEAB resulted in both significant
      activation and restoration of the pKa of Lys 115 to 5.9. These data support
      Westheimer's hypothesis that the pKa of the Schiff base-forming Lys 115 is
      decreased by its spatial proximity to the epsilon-ammonium group of Lys 116.

PMID- 8555197
TI  - Photoaffinity labeling of the active site of the Na+/K(+)-ATPase with 4-azido-2
      nitrophenyl phosphate.
AB  - Na+/K(+)-ATPase will hydrolyze small acylphosphates such as p-nitrophenyl
      phosphate (pNPP) in addition to ATP and can derive sufficient energy from the
      hydrolysis of these small molecules to catalyze active ion transport. In this
      report, 4-azido-2-nitrophenyl phosphate (ANPP), a photoreactive analog of pNPP,
      was used as a probe of the substrate binding site of dog renal Na+/K(+)-ATPase.
      ANPP was slowly hydrolyzed by Na+/K(+)-ATPase with a Vmax of 0.19 mumol mg-1 min
      1 and with an apparent Km of 1.0 mM. The Km for hydrolysis of pNPP was 1.7 mM.
      ANPP competitively inhibited the hydrolysis of pNPP with a Ki of 0.37 mM. Both
      the ATPase and pNPPase activity of the Na+/K(+)-ATPase were irreversibly
      inhibited after photolysis of the enzyme and ANPP with UV light, although neither
      activity was completely inhibited by up to 200 microM ANPP. Inhibition of
      activity was prevented by including 0.2 mM ATP in the reaction or by excluding
      Mg2+ from the photolysis buffer. Photolysis with [32P]ANPP labeled only the alpha
      subunit of the Na+/K(+)-ATPase, and the amount of labeling was substantially
      reduced by 0.2 mM ATP or in the absence of Mg2+. The stoichiometry of labeling
      extrapolated to a maximum of about 1.2 nmol/mg of protein at 100% inhibition of
      Mg(2+)-dependent activity. Limited proteolytic digestion showed labeling sites on
      nonoverlapping tryptic peptides derived from the alpha subunit of Na+/K(+)
      ATPase, and two radiolabeled peptides were purified from an exhaustive tryptic
      digest of [32P]ANPP-labeled Na+/K(+)-ATPase. One peptide contained amino acids
      Met-379 to Lys-406, and the second contained amino acids Ala-655 to Lys-676.
      Amino acids corresponding to Asn-398 and Pro-668 were missing from the sequences
      and may represent residues derivatized by ANPP from within the substrate binding
      site of Na+/K(+)-ATPase.

PMID- 8555198
TI  - Flavin-dependent alkyl hydroperoxide reductase from Salmonella typhimurium. 1.
      Purification and enzymatic activities of overexpressed AhpF and AhpC proteins.
AB  - The two components, AhpF and AhpC, of the Salmonella typhimurium alkyl
      hydroperoxide reductase enzyme system have been overexpressed and purified from
      Escherichia coli for investigations of their catalytic properties. Recombinant
      proteins were isolated in high yield (25-33 mg per liter of bacterial culture)
      and were shown to impart a high degree of protection against killing by cumene
      hydroperoxide to the host E. coli cells. We have developed quantitative enzymatic
      assays for AhpF alone and for the combined AhpF/AhpC system which have allowed us
      to address such issues as substrate specificity and inhibition by thiol reagents
      for each protein. All assays gave identical results whether overexpressed S.
      typhimurium proteins from E. coli or proteins isolated directly from S.
      typhimurium were used. Anaerobic hydroperoxide reductase assays have demonstrated
      that cumene hydroperoxide, ethyl hydroperoxide, and hydrogen peroxide can all be
      reduced by the combined enzyme system. AhpF possesses multiple pyridine
      nucleotide-dependent activities [5,5'-dithiobis(2-nitrobenzoic acid) (DTNB)
      reductase, oxidase, transhydrogenase, and, in the presence of AhpC, peroxide
      reductase activities]. Although AhpF can use either NADH or NADPH as the electron
      donor for these activities, NADH is the preferred reductant (Km,app of AhpF for
      NADH was more than 2 orders of magnitude lower than that for NADPH when analyzed
      using DTNB reductase assays). Thiol-modifying reagents react readily with each
      reduced protein, leading to complete loss of hydroperoxide and DTNB reductase
      activities. In contrast, thiol modification of reduced AhpF does not affect
      transhydrogenase or oxidase activities. These data provide the first direct
      evidence for a catalytic mechanism for peroxide reduction involving redox-active
      disulfides within each protein.

PMID- 8555199
TI  - Flavin-dependent alkyl hydroperoxide reductase from Salmonella typhimurium. 2.
      Cystine disulfides involved in catalysis of peroxide reduction.
AB  - The two-component alkyl hydroperoxide reductase enzyme system from Salmonella
      typhimurium catalyzes the pyridine nucleotide-dependent reduction of alkyl
      hydroperoxide and hydrogen peroxide substrates. This system is composed of a
      flavoenzyme, AhpF, which is related to the disulfide-reducing enzyme thioredoxin
      reductase, and a smaller protein, AhpC, which lacks a chromophoric cofactor. We
      have demonstrated that NADH-linked reduction of AhpF under anaerobic conditions
      converts two cystine disulfide centers to their dithiol forms. The AhpC cystine
      disulfide center, shown to exist as an intersubunit disulfide bond, is
      stoichiometrically reducible by NADH in the presence of a catalytic amount of
      AhpF and can be reoxidized by ethyl hydroperoxide. Disulfide bridges within
      oxidized AhpF form between Cys129 and Cys132 and between Cys345 and Cys348; the
      two C-terminal half-cystine residues, Cys476 and Cys489, exist as free thiol
      groups in oxidized AhpF and play no role in catalysis. Removal of the N-terminal
      202-amino acid segment containing the Cys129-Cys132 disulfide center obliterates
      the ability of AhpF to transfer electrons to 5,5'-dthiobis(2-nitrobenzoic acid)
      (DTNB) and AhpC. NADH added anaerobically to AhpF causes spectral changes
      consistent with preferential reduction of both disulfides relative to flavin
      reduction; the reduction potentials of the disulfide centers are thus
      appropriately poised for electron transfer from NADH and flavin to disulfide
      containing substrates (AhpC or DTNB), and ultimately to peroxides from AhpC.
      Blue, neutral flavin semiquinone is also generated in high yields during
      reductive titrations (91% yield during dithionite titrations), although the
      relatively slow formation of this species indicates its catalytic incompetence. A
      long wavelength absorbance band beyond 900 nm attributable to an FADH2-->NAD+
      charge transfer interaction is generated during NADH, but not dithionite,
      titrations and may be indicative of a species directly involved in the catalytic
      cycle. A catalytic mechanism including the transient formation of cysteine
      sulfenic acid within AhpC is proposed.

PMID- 8555200
TI  - Ionization equilibria for side-chain carboxyl groups in oxidized and reduced
      human thioredoxin and in the complex with its target peptide from the
      transcription factor NF kappa B.
AB  - The pH dependence of the 13C chemical shifts of the side-chain carboxyl carbons
      of all Asp and Glu residues in the reduced and oxidized states of human
      thioredoxin and in a mixed disulfide complex of human thioredoxin with a target
      peptide from the transcription factor NF kappa B has been investigated by
      multidimensional triple-resonance NMR spectroscopy. While the titration curves
      for most of the side-chain carboxyl resonances exhibit simple Henderson
      Hasselbalch behavior with pKa values not far from those found for model
      compounds, several side chains give rise to two- or three-step titration curves,
      indicative of the influence of multiple ionizations. In particular, the triad
      formed by Asp58, Asp60, and Asp61 forms such a complex network of titrating
      groups. The ionization behavior of Asp26 shows an abnormally high pKa value for
      an aspartate residue in all states of human thioredoxin, with pKa values of 9.9
      in the reduced state, 8.1 in the oxidized state, 8.9 in the mixed disulfide
      complex, and 8.6 in an active site mutant in which Cys35 was replaced by Ala. The
      unambiguous determination of the pKa values of Asp26 for a variety of states of
      human thioredoxin presented in this paper is highly significant in view of two
      recent reports on Escherichia coli thioredoxin which presented contradicting pKa
      values for Asp26 and Cys35 [Wilson et al. (1995) Biochemistry 34, 8931-8939; Jeng
      et al. (1995) Biochemistry 34, 10101-10105]. The stabilization of the protonated
      side chain of Asp26 in human thioredoxin is achieved via a hydrogen-bonding
      network involving the hydroxyl group of the neighboring Ser28 which is then
      connected to the active site region (comprising Cys32 and Cys35) via bound water
      molecules. The coupling of the buried Asp26 to the active site is responsible for
      the influence of the Asp26 ionization behavior on the titration shifts of active
      site residues.

PMID- 8555201
TI  - Microcirculating system for simultaneous determination of Raman and absorption
      spectra of enzymatic reaction intermediates and its application to the reaction
      of cytochrome c oxidase with hydrogen peroxide.
AB  - A new high-performance device for Raman/absorption simultaneous determination was
      developed. This was combined with a newly designed microcirculating system and
      was successfully applied to study intermediates in the reaction of bovine
      oxidized cytochrome c oxidase (CcO) with hydrogen peroxide under steady state
      conditions at ambient temperatures. Measurements with this device made it
      possible to correlate directly the species defined in terms of the visible
      absorption characteristics with specific Raman bands. The "607 nm" form of the
      enzyme obtained with H2(16)O2 gave an oxygen isotope sensitive band at 804 cm-1
      (769 cm-1 with H2(18)O2) in the Soret excited resonance Raman (RR) spectrum. Its
      frequency and isotope frequency shifts are exactly the same as those observed
      previously with 607 nm excitation in nonsimultaneous measurements for the 607 nm
      form, for which the presence of an oxoiron heme was demonstrated. The so-called "
      580 nm" form of the enzyme obtained with H2(16)O2 gave the main oxygen isotope
      sensitive band at 785 cm-1 (750 cm-1 with H2(18)O2) but appeared to consist of
      multiple species. This band was assigned to the FeIV = O stretching mode of
      ferryloxo heme on the basis of its isotopic frequency shift. Another oxygen
      isotope sensitive band was found at 355 cm-1 (340 cm-1 for H2(18)O2), similar to
      the case of dioxygen reaction. Temporal behavior of this band did not agree with
      either that of the 804 cm-1 band or that of the 785 cm-1 band but seemed to grow
      between the two species. The RR spectra in the higher frequency region of the 607
      nm and 580 nm forms excited at 427 nm were quite alike and did not support the
      formation of a porphyrin pi-cation radical.

PMID- 8555202
TI  - Interpretation of transient-state kinetic isotope effects.
AB  - In contrast to steady-state kinetic isotope effects (KIE's), transient-state
      KIE's are dependent on both time and signal source. We developed a theory which
      predicts the behavior of transient-state KIE's, permits the calculation of the
      intrinsic KIE, and makes possible the assignment of various optical signals to
      either pre- or post-hydride transfer events. We proved that the behavior of
      KIEobs for a reversible two-step reaction for all possible values of the rate
      constants and all possible ratios of intermediate and product contributions obeys
      three simple rules (assuming that the isotope-sensitive step involves a hydride
      transfer): (1) If only the post-hydride species contributes to the observed
      signal, KIEobs = KIEint at t = 0 and then decreases with time. (2) If only the
      pre-hydride species contributes to the observed signal, then KIEobs = 1 at t = 0
      and then decreases with time. (3) If both pre- and post-hydride species
      contribute to the observed signal, then KIEobs = 1 at t = 0 and then will either
      rise or fall with time depending on the relative molar signal coefficients of the
      pre- and post-hydride species. We provide experimental evidence that the
      phenomena predicted by this theory do in fact occur in enzyme-catalyzed
      reactions.

PMID- 8555203
TI  - A difference in the sequence of steps in the reactions catalyzed by two closely
      homologous forms of glutamate dehydrogenase.
AB  - Glutamate dehydrogenase from beef liver (bl GDH) and the corresponding enzyme
      from Clostridium symbiosum (cs GDH) each catalyze the same sequence of chemical
      events in the oxidative deamination of L-glutamate. This catalysis involves
      interactions between at least six conserved functional groups, each of which
      appears to occupy the same geometric position with respect to the substrate
      molecule in both enzyme--coenzyme--L-glutamate reactive ternary complexes. In
      both cases steady-state V/K pH profiles indicate the requirement for the transfer
      to the solvent of a single proton from the same abnormal lysine for L-glutamate
      to bind and react; the pK of that lysine is the same for both enzymes. Here we
      report studies of the proton traffic between enzyme and solvent using direct pH
      stat back-titration and indicator dye measurements on dead-end inhibitor ternary
      complexes, simultaneous transient-state time courses of proton and product, and
      transient-state kinetic isotope studies on both enzymes. We find that in the cs
      GDH catalyzed reaction the single proton is released only after the hydride
      transfer step whereas in the bl GDH reaction this proton release occurs prior to
      the hydride transfer step, despite the fact that the substrate molecule undergoes
      the same sequence of chemical events in both reactions. Interpreting these
      results in the context of the X-ray crystallographic structures of cs GDH and its
      NAD binary complex and of thermodynamic studies of bl GDH and its complexes, we
      conclude that the difference in the relative times of proton release in the two
      enzyme-catalyzed reactions must be ascribed to a difference in the sequence of
      active site cleft-opening and -closing events in the two identical reaction
      sequences. We suggest a possible biological significance to this unusual method
      of modulating a common reaction to suit differing metabolic roles.

PMID- 8555205
TI  - Correlation between dynamics and high affinity binding in an SH2 domain
      interaction.
AB  - Protein-protein interfaces can consist of interactions between large numbers of
      residues of each molecule; some of these interactions are critical in determining
      binding affinity and conferring specificity, while others appear to play only a
      marginal role. Src-homology-2 (SH2) domains bind to proteins containing
      phosphorylated tyrosines, with additional specificity provided by interactions
      with residues C-terminal to the phosphotyrosine (pTyr) residue. While the C
      terminal SH2 domain of phospholipase C-gamma 1 (PLCC SH2) interacts with eight
      residues of a pTyr-containing peptide from its high affinity binding site on the
      beta-platelet-derived growth factor receptor, it can still bind tightly to a
      phosphopeptide containing only three residues. Novel deuterium (2H) based nuclear
      magnetic resonance (NMR) spin relaxation experiments which probe the nanosecond
      picosecond time scale dynamics of methyl containing side chain residues have
      established that certain regions of the PLCC SH2 domain contacting the residues C
      terminal to the pTyr have a high degree of mobility in both the free and peptide
      complexed states. In contrast, there is significant restriction of motion in the
      pTyr binding site. These results suggest a correlation between the dynamic
      behavior of certain groups in the PLCC SH2 complex and their contribution to high
      affinity binding and binding specificity.

PMID- 8555204
TI  - Inactivation of inosine 5'-monophosphate dehydrogenase by the antiviral agent 5
      ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide 5'-monophosphate.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in de
      novo guanine nucleotide biosynthesis. IMPDH converts inosine 5'-monophosphate
      (IMP) to xanthosine 5'-monophosphate (XMP) with concomitant conversion of NAD+ to
      NADH. The antiviral agent 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide
      (EICAR) is believed to inhibit IMPDH by forming an active metabolite, the 5'
      monophosphate EICARMP. The experiments reported here demonstrate that EICARMP
      irreversibly inactivates both human type II and Escherichia coli IMPDH. IMPDH is
      protected from EICARMP inactivation by IMP, but not by NAD+. Further,
      denaturation/renaturation of the EICARMP-inactivated enzyme did not restore
      enzyme activity, which indicates that EICARMP forms a covalent adduct with IMPDH.
      EICARMP was successfully used to titrate the active sites of IMPDH; these
      experiments demonstrate that four active sites are present in an IMPDH tetramer.
      Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass
      spectrometry of native E. coli IMPDH established that protein translation
      initiates at the third ATG of the DNA sequence. Thus, the E. coli IMPDH monomer
      is only 488 amino acids long and contains five instead of six cysteines. In
      addition, MALDI-TOF mass spectrometry showed that EICARMP is covalently bound to
      Cys-305 (Cys-331 in human type II IMPDH numbering), suggesting that Cys-305
      functions as a nucleophile in the IMPDH reaction. The inactivation of the E. coli
      enzyme is a single-step reaction with kon = 1.94 x 10(4) M-1 s-1. In contrast,
      the inactivation of human type II IMPDH involves a two-step mechanism where Ki =
      16 microM, k2 = 2.7 x 10(-2) s-1 and kon = 1.7 x 10(3) M-1 s-1. These results
      demonstrate that significant differences exist between bacterial and human IMPDH
      and suggest that this enzyme may be a target for antibiotic drugs.

PMID- 8555206
TI  - Synthesis and structure determination by NMR of a putative vacuolar targeting
      peptide and model of a proteinase inhibitor from Nicotiana alata.
AB  - NA-proPI is a 40.3-kDa multidomain precursor protein found in the stigma of the
      ornamental tobacco Nicotiana alata. It is selectively targeted to the vacuole
      and, as the plant matures, is processed to produce a series of five 6-kDa
      proteinase inhibitors (one chymotrypsin and four trypsin reactive sites) which
      are thought to play a vital role in plant protection against insect pests. A
      putative sixth domain with a chymotrypsin reactive site is likely to be formed by
      three disulfide bridges linking the N- and C-terminal fragments of NA-proPI. This
      domain contains two distinct structural elements: a 54-residue sequence with high
      identity to each of the five repeated PI domains, and a nonrepeated 25-residue
      sequence at the C-terminus which is proposed to contain a vacuolar targeting
      peptide. The structure of the putative sixth domain was predicted using a
      combination of secondary structure prediction and homology modeling based on the
      known structure of one of the intact domains. A 26-residue peptide corresponding
      to the nonrepeated C-terminal sequence and encompassing the putative vacuolar
      targeting sequence was synthesized and its structure determined using 1H NMR
      spectroscopy and simulated annealing calculations. The peptide was found to adopt
      an amphipathic helical structure. The calculations based on NOE data suggested
      that the helix is curved, with a hydrophobic concave face and a hydrophilic
      convex face. This curvature is consistent with an observed periodicity in
      backbone NH chemical shifts. The structure of the entire sixth domain was modeled
      by combining the experimentally determined structure of the putative vacuolar
      targeting peptide with the homology model of the PI domain. In this model the
      alpha-helix of the putative targeting peptide protrudes from the otherwise
      compact PI domain. This observation is consistent with the requirement for
      targeting sequences to be relatively exposed for recognition by the sorting
      apparatus. As there is no consensus on the structure of vacuolar targeting
      sequences, this study provides a valuable insight into their potential mechanism
      of interaction with the cellular sorting apparatus.

PMID- 8555207
TI  - Fluorescent analogs of cyclic ADP-ribose: synthesis, spectral characterization,
      and use.
AB  - Cyclic ADP-ribose (cADPR) is a Ca(2+)-mobilizing cyclic nucleotide derived from
      NAD+. Accumulating evidence indicates that it is an endogenous modulator of the
      Ca(2+)-induced Ca2+ release mechanism in cells. In this study, we show that ADP
      ribosyl cyclase catalyzes the cyclization of not only NAD+ but also several of
      its analogs with various purine bases (guanine, hypoxanthine, or xanthine)
      substituting for adenine. Unlike cADPR, the resulting cyclic products are
      fluorescent. Comparisons with various model compounds indicate that only 7-methyl
      substituted purine nucleosides and nucleotides are fluorescent, and the pH
      dependence of their UV spectra is most similar to that of the fluorescent cADPR
      analogs, indicating that the site of cyclization of these analogs is at the N7
      position of the purine ring. This finding is novel since the site of cyclization
      is at the N1-position for cADPR as determined by X-ray crystallography. That a
      single enzyme can cyclize a variety of substrates at two different sites has
      important implications mechanistically, and a model is proposed to account for
      these novel catalytic properties. Among the analogs synthesized, cyclic GDP
      ribose is highly resistant to hydrolysis, while cyclic IDP-ribose can be readily
      hydrolyzed by CD38, a bifunctional enzyme involved in the metabolism of cADPR.
      These unique properties of the analogs can be used to develop fluorimetric assays
      for monitoring separately the cyclization and hydrolytic reactions catalyzed by
      the metabolic enzymes of cADPR. The convenience of the method in measuring
      kinetic parameters, pH-dependence, and modulator activity of the metabolic
      enzymes of cADPR is illustrated.

PMID- 8555208
TI  - Factors that affect the stabilization of alpha-helices in short peptides by a
      capping box.
AB  - It was reported recently that the capping box sequences of four N-terminal
      residues are very important for the stabilization of alpha-helices in proteins
      and peptides. To elucidate factors that affect the stabilization of alpha-helices
      in short peptides by this motif, we analyzed conformational properties of side
      chains of five N-terminal residues in several analogs of neuropeptide Y (NPY).
      The analysis revealed three previously unreported factors that appear to be
      important for stabilization of an alpha-helix: (a) a second capping box hydrogen
      bond for the side chains of Ser, Thr, and Cys; (b) long-range electrostatic
      interactions between the first (N-cap) and fifth (N4) residues; and (c) capping
      interactions of alpha-amino groups with the N4 residue. These factors were
      incorporated into the parameter set of a recently published, statistical
      mechanics approach that showed excellent accuracy in the prediction of the
      helical propensities of short peptides in water [Munoz, V., & Serrano, L. (1995)
      J. Mol. Biol. 245, 275-296, 297-308]. A significant improvement in the agreement
      between theoretical predictions and experimental data was achieved. The present
      results also clarify the nature of capping box stabilization of alpha-helices in
      peptides and proteins, indicating that the total influence of hydrogen bonding,
      local interactions between side chains, helix macrodipole--charge/dipole
      interactions, and solvation possibilities must all be taken into account. All
      these factors are associated with approximately the same energy, but with
      different residues at the N-cap position, they may have opposite effects on the
      helix stability of peptides. Thus, a delicate balance of interactions of
      different types controls the stabilization properties of N-cap residues in alpha
      helices.

PMID- 8555209
TI  - Contribution of cutinase serine 42 side chain to the stabilization of the
      oxyanion transition state.
AB  - Cutinase from the fungus Fusarium solani pisi is a lipolytic enzyme able to
      hydrolyze both aggregated and soluble substrates. It therefore provides a
      powerful tool for probing the mechanisms underlying lipid hydrolysis. Lipolytic
      enzymes have a catalytic machinery similar to those present in serine
      proteinases. It is characterized by the triad Ser, His, and Asp (Glu) residues,
      by an oxyanion binding site that stabilizes the transition state via hydrogen
      bonds with two main chain amide groups, and possibly by other determinants. It
      has been suggested on the basis of a covalently bond inhibitor that the cutinase
      oxyanion hole may consist not only of two main chain amide groups but also of the
      Ser42 O gamma side chain. Among the esterases and the serine and the cysteine
      proteases, only Streptomyces scabies esterase, subtilisin, and papain,
      respectively, have a side chain residue which is involved in the oxyanion hole
      formation. The position of the cutinase Ser42 side chain is structurally
      conserved in Rhizomucor miehei lipase with Ser82 O gamma, in Rhizopus delemar
      lipase with Thr83 O gamma 1, and in Candida antartica B lipase with Thr40 O gamma
      1. To evaluate the increase in the tetrahedral intermediate stability provided by
      Ser42 O gamma, we mutated Ser42 into Ala. Furthermore, since the proper
      orientation of Ser42 O gamma is directed by Asn84, we mutated Asn84 into Ala,
      Leu, Asp, and Trp, respectively, to investigate the contribution of this indirect
      interaction to the stabilization of the oxyanion hole. The S42A mutation resulted
      in a drastic decrease in the activity (450-fold) without significantly perturbing
      the three-dimensional structure. The N84A and N84L mutations had milder kinetic
      effects and did not disrupt the structure of the active site, whereas the N84W
      and N84D mutations abolished the enzymatic activity due to drastic steric and
      electrostatic effects, respectively.

PMID- 8555210
TI  - Extension of the polarity-dependent "switch phenomenon" of the gp120 binding
      domain as a target for antiviral chemotherapy.
AB  - A 15-residue fragment within the major continuous domain of gp120 from HIV-1 that
      can bind independently to the CD4 receptor has been shown to have the property of
      behaving as a solvent polarity-dependent conformational switch. The switch
      behavior (cooperative transition from beta-sheet to helical conformation as a
      function of solvent polarity), which is conserved among strains with the widest
      sequence variability possible, appears to be a prerequisite for the CD4-binding
      ability. A number of switch inhibitors have been identified that destroy the
      conformational switch in the 15-residue fragment and concurrently its ability to
      bind to CD4-expressing cells. It can now be shown that the switch behavior and
      its inhibition by substances with certain shared structural characteristics are
      not restricted to the 15-residue subfragment, but are reflected by the behavior
      of the entire 44-residue binding domain. Further, substances active as switch
      inhibitors have an immediate effect on the conformation of the 44-residue
      fragment in aqueous buffer whereas inactive substances do not. The predictive
      value of this as a screening method is demonstrated in testing a number of new
      potential switch inhibitory compounds.

PMID- 8555211
TI  - Solution structure of LSIII, a long neurotoxin from the venom of Laticauda
      semifasciata.
AB  - We report the sequence-specific proton assignments and solution structure of the
      long neurotoxin LSIII from the venom of Laticauda semifasciata determined by two-
      and three-dimensional 1H NMR. Input for structure calculations consisted of 497
      NOE-derived distance restraints and 45 dihedral angle restraints obtained from J
      couplings. A two-particle-per-residue representation of protein structure was
      used to generate 200 initial structures which were then subjected to all-atom
      refinement by simulated annealing. Twenty-three final structures consistent with
      the experimental restraints were obtained; the average atomic RMS difference
      between the individual structures and the mean structure was 0.82 A for the
      backbone heavy atoms and 1.3 A for all heavy atoms (residues 1-26, 37-60). The
      main elements of regular secondary structure are a three-stranded antiparallel
      beta-sheet and three finger-like loops protruding from a globular core,
      consistent with previously reported structures of long neurotoxins. The end of
      the prominent loop II, which is involved in binding to acetylcholine receptor, is
      disordered relative to the rest of the molecule. A novel finding of this study is
      that the loop has a well defined local structure; this and other observations
      suggest this region moves as a rigid body. We propose that this motion is a
      heretofore unrecognized general feature of long neurotoxins, with specific
      consequences for binding to the acetylcholine receptor.

PMID- 8555212
TI  - Independent modulation of the activity of alpha-ketoglutarate dehydrogenase
      complex by Ca2+ and Mg2+.
AB  - The activity of alpha-ketoglutarate dehydrogenase complex (KGDHC), an important
      enzyme regulating several metabolic pathways, could be regulated by changes in
      the environment within the mitochondrial matrix. It has been postulated that the
      activity of this and other dehydrogenases in vivo could be modulated by changes
      in the intramitochondrial concentrations of Ca2+ or Mg2+. Using a purified alpha
      ketoglutarate dehydrogenase from pig hearts, the effect of Ca2+ and/or Mg2+ on
      the enzyme activity was investigated. Either Ca2+ or Mg2+ increased enzyme
      activity, and the effects were additive if the concentrations of free divalent
      cations were below 0.1 and 1 mM for Ca2+ and Mg2+, respectively. In the presence
      of 1 mM alpha-ketoglutarate and other cofactors, the KM for Mg2+ was 25 microM
      and less than 1 microM for Ca2+. The KM for alpha-ketoglutarate was a function of
      the divalent cation(s) present: 4 +/- 1.1 mM in the absence of Ca2+, with or
      without Mg2+; 2.2 mM in the presence of 1.8 microM Ca2+ alone; and 0.3 mM in the
      presence of both Ca2+ and Mg2+. Mg2+ increased KGDHC activity only in the
      presence of thiamine pyrophosphate (TPP) indicating that KGDHC requires both TPP
      and Mg2+ for enzyme's maximal activity. The affinity of KGDHC for NAD+ is
      significantly changed by either Mg2+ or Ca2+. The conclusions are that changes in
      both Ca2+ and Mg2+, in concentrations possibly occurring within mitochondria,
      could control KGDHC activity and that thiamine pyrophosphate is required for
      maximal enzyme activity.

PMID- 8555214
TI  - Redox dependent interactions of the metal sites in carbon monoxide-bound
      cytochrome c oxidase monitored by infrared and UV/visible spectroelectrochemical
      methods.
AB  - Spectroelectrochemical titration studies involving the binding of the infrared
      active probe ligand carbon monoxide (CO) to the heme alpha 3/CuB site of bovine
      heart cytochrome c oxidase (CcO) have been reexamined. The spectroelectrochemical
      cell employed was constructed to monitor both the infrared (IR) and visible/Soret
      spectra of the CcO-CO complex as a function of the overall oxidation state of the
      enzyme. A number of commonly used electron transfer mediators were employed to
      shuttle electrons between the redox active sites within the enzyme and the
      electrode surface. The well-documented shift in the CO infrared stretch band
      maximum from 1963.3 cm-1 (CcO fully reduced) to 1965.5 cm-1 (CcO partially
      oxidized) was carefully titrated electrochemically. Deconvolution of the
      asymmetric CO stretches indicates the existence of two different states of CO
      vibrators within the enzyme, presumably due to two conformers which are present
      in a ratio of approximately 5:1. Upon incrementally stepping the potential from
      the fully reduced state to the partially oxidized state, we found it possible to
      follow the decrease in the intensity of the original pair of these conformers and
      the concomitant increase of a resultant pair while maintaining this 5:1 ratio
      between the conformers. By plotting the change in the deconvoluted CO peak
      intensities vs the redox potential, as well as the absorbance changes in the
      visible/Soret spectra vs the redox potential, we found not only that both fit an
      n = 1 electron process but also that the spectral changes tracked each other
      identically with experimental error. Furthermore, analysis of the second
      derivative of the Soret spectra allowed for the qualitative monitoring of the
      oxidation state of the Fe alpha site which again tracked identically to that of
      the CO shift in the IR region. These results would seem to confirm earlier
      suggestions that perturbing the oxidation state of Fe alpha causes a
      conformational change in the enzyme which affects the binding site for CO, namely
      heme alpha 3. As a consequence of the CO IR stretching frequencies changing by
      only 2 cm-1 during this redox titration, with no accompanying changes in half
      band width, we suggest that it is impossible that this small but significant
      change seen in the CO stretching frequencies could be due to an oxidation state
      change in CuB, given the known sensitivity of the CO stretching frequency to
      perturbations and the close proximity of Cu(B) to the CO binding site at heme
      alpha 3 (4.5 A). Therefore, it would appear that Cu(B) must remain reduced as
      long as CO is bound to the heme alpha 3 site. This is consistent with earlier
      proposals that Fe alpha 3 and Cu(B) are acting together as a two-electron donor
      to dioxygen.

PMID- 8555213
TI  - Phosphotransfer and CheY-binding domains of the histidine autokinase CheA are
      joined by a flexible linker.
AB  - Multidimensional heteronuclear NMR techniques were applied to study a protein
      fragment of the histidine autokinase CheA from Escherichia coli. This fragment
      (CheA1-233) contains the phosphotransfer domain and the CheY-binding domain
      joined by a linker region. Comparison of chemical shift and NOE cross-peak
      patterns indicates that the structures of the two domains in CheA1-233 remain
      nearly the same as in the two individual domain fragments, CheA1-134 and CheA124
      257. Relaxation properties of the backbone 15N nuclei were measured to study the
      rotational correlations of the two domains and properties of the linker region.
      Dynamics data were analyzed both by an isotropic motional model and an
      anisotropic motional model. The experimental T1 and T2 values, the derived
      rotational correlation times, and motional anisotropy are significantly different
      for the two domains, indicating the two domains reorient independently and the
      linker region is highly flexible. Dynamics data of CheA1-233 were also compared
      with those of CheA1-134. Our studies show that flexible domain linkers and
      extended and flexible terminal polypeptide chains can have significant effects on
      the motional properties of the adjacent structured regions. These observations
      suggest a model for the graded regulation of CheA autophosphorylation activity.
      In this model, the various activity states of the receptor are generated by
      controlling the access of the mean position of the kinase domain to the
      phosphotransfer domain. This would then modulate the diffusional encounter rate
      of the domains and hence activity over a wide and graded range of values.

PMID- 8555215
TI  - Cytochrome c peroxidase complexed with cytochrome c has an unperturbed heme
      moiety.
AB  - Transient resonance Raman, Raman difference, circular dichroism (CD), and optical
      absorption studies have been carried out on the electrostatic complexes formed by
      yeast cytochrome c peroxidase (CCP) with horse cytochrome c (Cytc) in low ionic
      strength solutions. In all the complexes examined [e.g., CCP(II)/Cytc(II),
      CCP(III)/Cytc(II), CCP(III)/Cytc(III)], the local heme environments of both
      proteins are largely unperturbed upon complexation. Specifically, CCP preserves a
      completely pentacoordinate high-spin heme in both its ferric and ferrous forms in
      CCP/Cytc complexes and uncomplexed mixtures. We found no evidence corroborating
      the previously reported increase in the low-spin fraction of CCP heme upon
      complexation with Cytc [Hildebrandt et al. (1992) Biochemistry 31, 2384-2392].
      Instead, our Raman data strongly suggest that the H-bonding networks in the
      distal and proximal pockets of CCP are well maintained in the complexes. On the
      other hand, CD spectra of CCP(III)/Cytc(III) complexes showed substantial
      variations (relative to the uncomplexed mixtures) in the far-UV region,
      reflecting some protein conformational rearrangements. In addition, the spectral
      data suggest that complexation with Cytc affects the previously observed pH
      dependent flexibility of the heme structure of CCP and thus influences the
      photodynamics of the CCP active site.

PMID- 8555216
TI  - Cytochrome P450-dependent transformations of 15R- and 15S
      hydroperoxyeicosatetraenoic acids: stereoselective formation of epoxy alcohol
      products.
AB  - Although there are many reports of epoxy alcohol synthesis from lipoxygenase
      products (fatty acid hydroperoxides) in mammalian tissues, there are no well
      defined examples of the stereoselective synthesis of individual epoxy alcohol
      diastereomers. An earlier report on the metabolism of 15S
      hydroperoxyeicosatetraenoic acid (15S-HPETE) in rat liver microsomes suggested
      such a specific reaction [Weiss, R. H., et al. (1987) Arch. Biochem. Biophys.
      252, 334-338]. To characterize this reaction further, we set out to determine the
      precise structures and mechanism of biosynthesis of the epoxy alcohol products.
      We compared the products formed from 15R- and 15S-HPETE by hematin (a
      nonenzymatic reaction), by liver microsomes isolated from control and
      phenobarbital-treated rats, and by purified cytochrome P450 2B1. Eight epoxy
      alcohol isomers were identified by mass spectrometry and 1H NMR. In the hematin
      reaction, the major products are four epoxy alcohols with the epoxide in the
      trans configuration, diastereomers are formed in similar amounts, and the 15
      HPETE enantiomers give indistinguishable patterns of products. By contrast, the
      liver microsomes and P450 2B1 enzyme form predominantly single diastereomers, and
      the configuration of the epoxide is dependent on the stereochemistry of the
      substrate. The main product formed from 15S-HPETE is 11S-hydroxy-14S,15S-trans
      epoxyeicosa-5Z,8Z,12E- trienoic acid, and the amounts increase upon phenobarbital
      induction. The main products from 15R-HPETE are 11-hydroxy-14S,15R-epoxyeicosa
      5Z,8Z,12E-t rienoic acid from microsomes from control rats and 13-hydroxy-14S,15R
      cis-epoxyeicosa-5,8,11-trienoic acid in microsomes from phenobarbital-induced
      rats. The P450 2B1 enzyme gave products similar to those from the phenobarbital
      induced microsomes. Analysis of an incubation using the 18O-labeled 15S-HPETE
      substrate demonstrated 97.6% retention of both hydroperoxy oxygens in the major
      product with progressively lower 18O retentions in the minor products (74-32%),
      possibly reflecting degrees of enzymatic control of these reactions. These
      results establish a precedent for the stereoselective synthesis of epoxy alcohols
      by mammalian cytochrome P450s.

PMID- 8555217
TI  - Isolation of two forms of the nitrogenase VFe protein from Azotobacter
      vinelandii.
AB  - When Q-Sepharose was used in the purification of the V nitrogenase proteins from
      Azotobacter vinelandii, an increase in resolution was observed that resulted in a
      separation of the nitrogenase component 1 protein (Av1') into two forms, labeled
      Av1'A and Av1'B. Even though both forms possessed the same enzymatic behavior,
      Av1'A exhibited a lower specific activity and migrated during gel filtration with
      an apparent lower molecular weight than Av1'B. Furthermore, SDS-polyacrylamide
      gel electrophoresis showed different relative compositions of the two major
      subunits of both forms, with Av1'A possessing a trimer (alpha beta 2) pattern
      compared to the more typical tetramer (alpha 2 beta 2) pattern found for Av1'B.
      Metal analysis indicated a V-to-Fe ratio of 1:19 for Av1'A and 1:15 (or 2:30) for
      Av1'B, while acid-labile sulfide analysis showed that Av1'A possessed about half
      as much sulfide as Av1'B. EPR spectroscopy revealed that both proteins retained
      the S = 3/2 and S = 1/2 signals observed in earlier isolations, with an
      additional S = 1/2 signal present in the spectrum of protein A. These results
      suggest that Av1'A is an incomplete form of the VFe protein, containing only one
      cofactor and one P cluster with an additional [Fe4-S4]-like cluster. The presence
      of a V storage protein in A. vinelandii was also investigated. Although no V
      storage protein was found, two V-binding proteins were observed.

PMID- 8555218
TI  - Oxidative titration of the nitrogenase VFe protein from Azotobacter vinelandii:
      an example of redox-gated electron flow.
AB  - The nitrogenase VFe protein of Azotobacter vinelandii (Av1') has been shown to
      exist in two forms called Av1'A, which has a primary alpha beta 2 trimeric
      structure, and Av1'B, which has an alpha 2 beta 2 tetrameric structure
      [Blanchard, C. Z., & Hales, B. J. (1996) Biochemistry 35, 472-478]. Both forms
      exhibit S = 5/2 EPR signals in the as-isolated state that may be assigned to 1
      equiv-oxidized P clusters (P+). These signals are abolished by enzymatic
      reduction with the component 2 protein (Av2'). Stepwise oxidative titrations of
      enzymatically reduced Av1'B result in the restoration of the S = 5/2 P+ signals
      and the concurrent decrease of the S = 3/2 vanadium cofactor signal. Further
      oxidation results in the appearance of an integer spin signal assigned to the 2
      equiv-oxidized P cluster (P2+). Unlike the analogous signal previously observed
      in Mo nitrogenase component 1 (Av1), which arises from an excited state, the
      integer spin P2+ signal in Av1'B originates from a ground-state doublet. Similar
      oxidative titrations of enzymatically reduced Av1'A show redox behavior
      dramatically different from that of Av1'B, as monitored by EPR spectroscopy. We
      observed spectral evidence for a redox-induced intramolecular electron transfer
      between the reduced P cluster and the oxidized FeV cofactor cluster during the
      titrations.

PMID- 8555219
TI  - Effect of lipid molecular structure and gramicidin A on the core of lipid vesicle
      bilayers. A time-resolved fluorescence depolarization study.
AB  - We have investigated the molecular orientational order and reorientational
      dynamics of the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) in the core
      of the membrane bilayer. Vesicles of lipids of varying unsaturation and headgroup
      (POPC, DOPC, DLPC, DLLPC, EGGPG, DOPG, DGDG, and SQDG) were studied using the
      time-resolved fluorescence anisotropy of DPH. Generally, values of the second
      order parameter <P2> for DPH are found to be very small. However, this should not
      be interpreted as DPH having low orientational order as witnessed by large values
      of the next relevant order parameter <P4>. This implies considerable transverse
      populations of DPH molecules within the bilayer. In phosphatidylcholines with an
      acyl chain of 18 carbon atoms, the value of <P2> for DPH decreases with
      increasing lipid unsaturation and even attains negative values. No effect of the
      lipid headgroup on the order and dynamics of DPH is detected. Furthermore, we
      study the peptide-lipid interaction of the hydrophobic antibiotic gramicidin A
      (gA) in DOPC vesicles using DPH. The nonchannel conformation has an ordering
      effect on DPH in the bilayer core, which the channel confirmation lacks. This can
      be understood in terms of the geometrical shape of the gA dimer, as shown
      previously with the probes TMA-DPH and DPHPC [Muller, J. M., et al. (1995)
      Biochemistry 34, 3092]. We find that for DPH data the conventional Brownian
      rotational diffusion (BRD) model and the compound motion model (CMM) give
      equivalent fits. In this respect, DPH differs from TMA-DPH and DPHPC, for which
      probes only the CMM allowed a consistent interpretation of the molecular
      orientation.

PMID- 8555220
TI  - Membrane structure of voltage-gated channel forming peptides by site-directed
      spin-labeling.
AB  - Three spin-labeled derivatives of the voltage-gated peptide alamethicin were
      prepared with nitroxides at the C-terminal phenyalaninol, and at positions 9 and
      15 in the amino acid sequence. In addition, three spin-labeled derivatives of an
      analog of alamethicin where alpha-methylalanine residues are replaced by leucine
      were prepared with nitroxide labels at the same positions. Continuous wave power
      saturation EPR spectroscopy was used to examine the effect of molecular oxygen
      and water soluble paramagnetic reagents on the saturation behavior of the labeled
      peptides. Using the gradients of these species which exist through the membrane
      solution interface, distances for these nitroxide derivatives from the membrane
      solution interface were estimated. The distances show that alamethicin is
      inserted along the bilayer normal with the C-terminus of the peptide lying in the
      aqueous solution 3 or 4 A from the membrane interface. In this configuration
      alamethicin does not completely cross the bilayer, and the N-terminus of
      alamethicin is within the membrane hydrocarbon approximately 16 A from the
      phosphate groups on the opposing interface. The analog where leucines replace
      alpha-methylalanines shows a similar conformation, except that the entire peptide
      is translated 3-4 A deeper into the membrane than is native alamethicin. The
      distances that are measured for alamethicin using EPR are consistent with a
      linear high resolution NMR structure determined in SDS and the X-ray crystal
      structure. The membrane position and structure of alamethicin found here limit
      the likely models for voltage-gating of this peptide.

PMID- 8555221
TI  - Myosin subfragment 1 hydrophobicity changes associated with different nucleotide
      induced conformations.
AB  - Myosin subfragment 1 hydrophobicity was found to be sensitive to the occupancy
      and nature of bound nucleotide at its active site, as shown by changes in elution
      behavior of unmodified and chemically modified S1 during phenyl hydrophobic
      chromatography. The elution properties of S1 were unaltered by alkylation of SH1
      (Cys-707) with N-ethylmaleimide or by covalent bridging between SH1 and SH2 (Cys
      697) with p-phenylenedimaleimide with trapping of MgADP. Although addition of
      MgADP or MgATP to the elution buffers had minimal effect on the elution
      properties of these modified S1 species, the presence of these nucleotides was
      found to produce differential effects with unmodified S1. With MgADP, where S1 is
      in the S1** MgADP state, the elution times were decreased slightly, whereas with
      MgATP, where S1 is primarily in the S1** MgADP.Pi state, the elution times were
      significantly lowered, indicating reduced accessibility for the immobilized
      phenyl ligand. Stable S1 ternary complexes, formed with MgADP and various Pi
      analogues, showed elution times similar to that for S1 in the buffers containing
      MgATP. Thus, two main classes of nucleotide-induced S1 conformations can be
      defined according to their interaction with immobilized phenyl. These nucleotide
      induced changes in S1 hydrophobicity correlate well with reported changes in
      radius of gyration of S1 associated with different states of the bound nucleotide
      [Wakabayashi, K., Tokunga, M., Kohno, I., Sugimoto, Y.; Hamanaka, T., Takezawa,
      Y., Wakabayashi, T., & Amemiya, Y. (1992) Science 258, 443-447], suggesting that
      the observed hydrophobicity interaction may be measuring accessibility of the
      immobilized phenyl ligand into a hydrophobic crevice, and that this crevice is
      closed or tightened when S1 is in the S1** MgADP.Pi state.

PMID- 8555222
TI  - Functional expression of mammalian myosin I beta: analysis of its motor activity.
AB  - The motor function of vertebrate unconventional myosins is not well understood.
      In this study, we initiated the baculovirus expression system to characterize a
      novel myosin I from bovine adrenal gland that we had previously cloned [Zhu, T.,
      & Ikebe, M. (1994) FEBS Lett. 339, 31-36], which is classified as myosin I beta.
      The expressed myosin I beta was well extracted when calmodulin was coexpressed in
      Sf9 cells. The recombinant myosin I beta cosedimented with actin in an ATP
      dependent manner. The purified myosin I beta was composed of one heavy chain and
      three calmodulins. The electron microscopic image of myosin I beta confirmed its
      single-headed structure with a short tail, which is similar to that of brush
      border myosin I (BBMI). Myosin I beta showed high K+,EDTA--ATPase activity
      (approximately 0.14 mumol/min/mg) and Ca(2+)-ATPase activity (approximately 0.32
      mumol/min/mg), and the KCl/pH dependence of these activities was different from
      that of conventional myosin. Mg(2+)-ATPase activity of myosin I beta alone was
      increased above pCa 6, while the actin dependent activity was not affected by
      Ca2+. Actin sliding velocity of myosin I beta in the absence of Ca2+ was 0.3-0.5
      microns/s at 25 degrees C, which is much greater than that of BBMI (< 0.05
      microns/s). The actin sliding activity was abolished above pCa 6, and the sliding
      activity was restored when exogenous calmodulin was added in the absence of Ca2+.
      Within similar Ca2+ concentrations, one of the three calmodulins was dissociated
      from myosin I beta. The results suggest that Ca2+ dependent association of
      calmodulin may function as a regulatory mechanism of myosin I beta motor activity
      and that the motor activity of mammalian myosin I is largely different among
      distinct myosin I isoforms.

PMID- 8555223
TI  - Binding of S1(A1) and S1(A2) to F-actin.
AB  - The binding curve of myosin subfragment-1 (S1) to F-actin is not a simple
      hyperbola: at high concentrations of S1 the binding curve can be transformed into
      a linear plot ("normal" binding), but at small concentrations of S1 the binding
      complications deform the binding curve and produce nonlinear transforms
      ("anomalous" binding) [Andreev, O. A., & Borejdo, J. (1992) J. Muscle Res. Cell
      Motil. 13, 523-533]. This anomalous behavior may result either from the
      heterogeneity of S1 in regard to light chain isoforms or from the cooperativity
      between S1's. To distinguish between these possibilities we measured the affinity
      and the orientation of S1(A1) and S1(A2) with respect to F-actin. Affinity was
      measured in vitro by ultracentrifugation in the presence of F-actin, and
      orientation was measured in vivo by a combination of polarization of fluorescence
      and linear dichroism. We found that both the affinity and the orientation
      depended on the relative concentration of S1 isomer and actin: when S1 was in
      excess or was equimolar with actin (filament saturated with S1), each isomer
      bound F-actin with an affinity of 2 x 10(6) M-1 and was oriented approximately
      perpendicularly to the muscle axis. When actin was in excess (filament
      unsaturated with S1), each isomer bound F-actin with an affinity of 1.2 x 10(7) M
      1 and was oriented more parallel to the muscle axis. S1(A1) and S1(A2) labeled on
      the light chain had different polarizations when bound to unsaturated filaments
      but had the same polarizations when bound to saturated filaments. These results
      excluded heterogeneity as a reason for anomalous binding and suggested that
      binding occurred with negative cooperativity. We think that the negative
      cooperativity occurs when saturation of actin filaments with heads leads to the
      lack of vacant adjacent sites on a filament and a consequent prevention of S1
      binding to two actin protomers.

PMID- 8555224
TI  - Steady-state and time-resolved fluorescence studies on the ligand-induced
      conformational change in an active lysozyme derivative, Kyn62-lysozyme.
AB  - The ligand-induced conformational change of an active lysozyme derivative, Kyn62
      lysozyme, in which Trp62 of hen egg-white lysozyme (EC 3.2.1.17) was selectively
      modified to kynurenine, was investigated by steady-state and time-resolved
      fluorescence spectroscopy. Kyn62 formed an intramolecular energy transfer donor
      acceptor pair with a tryptophan residue as a donor. The energy transfer was
      related to the conformation of the active site. The spectral overlap integral (J)
      of the kynurenine-tryptophan pair is large as it was determined to be 4.92 x 10(
      15) M-1 cm3. Time-resolved fluorescence properties of Kyn62-lysozyme and its
      complex with a trimer of N-acetyl-D-glucosamine [(GlcNAc)3] show that the energy
      donor is Trp28 or Trp111 in the hydrophobic matrix box of the free Kyn62
      lysozyme. In the complex, it appears that the kynurenine residue drastically
      changed its orientation or approached closer to Trp108 to accept more efficiently
      the excitation energy from Trp108 on the binding of Kyn62-lysozyme with
      (GlcNAc)3.

PMID- 8555225
TI  - Selected cysteine point mutations confer mercurial sensitivity to the mercurial
      insensitive water channel MIWC/AQP-4.
AB  - The mercurial-insensitive water channel (MIWC or AQP-4) is a 30-32 kDA integral
      membrane protein expressed widely in fluid-transporting epithelia [Hasegawa et
      al. (1994) J. Biol. Chem. 269, 5497-5500]. To investigate the mercurial
      insensitivity and key residues involved in MIWC-mediated water transport, amino
      acids just proximal to the conserved NPA motifs (residues 69-74 and 187-190) were
      mutated individually to cysteine. Complementary RNAs were expressed in Xenopus
      oocytes for assay of osmotic water permeability (Pf) and HgCl2 inhibition dose
      response. Oocytes expressing the cysteine mutants were highly water permeable,
      with Pf values (24-33 x 10(-3) cm/s) not different from that of wild-type (WT)
      MIWC. Pf was reversibly inhibited by HgCl2 in mutants S70C, G71C, G72C, H73C, and
      S189C but insensitive to HgCl2 in the other mutants. K1/2 values for 50%
      inhibition of Pf by HgCl2 were as follows (in millimolar): 0.40 (S70C), 0.36
      (G71C), 0.14 (G72C), 0.45 (H73C), 0.24 (S189C), and > 1 for WT MIWC and the other
      mutants. To test the hypothesis that these residues are near the MIWC aqueous
      pore, residues 72 and 188 were mutated individually to the larger amino acid
      tryptophan. Pf in oocytes expressing mutants G72W or A188W (1.3-1.4 x 10(-3)
      cm/s) was not greater than that in water-injected oocytes even though these
      proteins were expressed at the oocyte plasma membrane as shown by quantitative
      immunofluorescence. Coinjection of cRNAs encoding WT MIWC and G72W or A188W
      indicated a dominant negative effect; Pf (x 10(-3) cm/s) was 22 (0.25 ng of WT),
      10 (0.25 ng of WT + 0.25 ng of G72W), and 12 (0.25 ng of WT + 0.25 ng of A188W).
      Taken together, these results suggest the MIWC is mercurial-insensitive because
      of absence of a cysteine residue near the NPA motifs and that residues 70-73 and
      189 are located at or near the MIWC aqueous pore. In contrast to previous data
      for the channel-forming integral protein of 28kDa (CHIP28), the finding of a
      dominant negative phenotype for mutants G72W and A188W indicates that MIWC
      monomers interact at a functional level.

PMID- 8555226
TI  - Angiogenin single-chain immunofusions: influence of peptide linkers and spacers
      between fusion protein domains.
AB  - The gene for human angiogenin (Ang), a member of the ribonuclease superfamily,
      was fused to a gene encoding a single-chain antibody (sFv) against the human
      transferrin receptor. Three Ang single-chain immunofusion proteins (AngsFvs) were
      constructed with variations in the type of linker connecting the VL and VH chain
      [EGKSSGSGSESKEF, L1 or (GGGGS)3, L2] as well as with or without a spacer (FB)
      connecting the Ang and sFv (AngFBsFvL1 or L2; AngsFv(L2)]. Although the nature of
      the linker did not affect the enzymatic activity of the FB-containing fusion
      proteins, the fusion protein containing the L2 linker was 2.3-fold more effective
      than the L1 linker in competing with the labeled monoclonal IgG1 antibody for
      binding to the transferrin receptor. The fusion protein containing the L2 linker
      without the FB spacer exhibited a 13-fold decrease in binding to the transferrin
      receptor as well as a decrease in its capacity to degrade tRNA and to inhibit
      translation in the rabbit reticulocyte lysate compared to its counterpart
      containing the FB spacer. Binding of placental ribonuclease inhibitor (PRI) to
      Ang also was affected by the nature of the linker and by the presence or absence
      of a spacer. PRI bound to Ang and AngFBsFv(L2) and inhibited their ribonuclease
      activity. A 3-fold greater concentration of PRI, however, did not affect the
      activity of AngFBsFv(L1) or AngsFv(L2), suggesting that the conformation of these
      fusion proteins was altered. Binding of monoclonal and polyclonal anti-Ang
      antibodies to AngsFvs was also used to investigate conformational alterations of
      the fusion proteins. AngFBsFv(L2) was the least altered while AngFBsFv(L1)
      exhibited the greatest change in structure. Yet maximal concentrations of all
      AngsFvs elicited angiogenesis in the chick chorioallantoic membrane assay,
      demonstrating that Ang in all three fusion proteins remained functionally active.
      Consistent with all the activities, the fusion protein containing the FB spacer
      and L2 linker was the most cytotoxic to three different human tumor cell lines.
      The fusion protein lacking the FB spacer exhibited the least cytotoxicity. These
      data demonstrate that the linker connecting the VH-VL chains can affect the
      binding and cellular cytotoxicity of Ang immunofusions and that placement of a
      spacer between the antibody binding domains and Ang is necessary for optimal
      activity. Thus, a new class of targeted therapeutic agents containing Ang as the
      toxic moiety can be designed that potentially will be less immunogenic and less
      toxic than immunotoxins available currently.

PMID- 8555227
TI  - Animal and plant cell lysates share a conserved chaperone system that assembles
      the glucocorticoid receptor into a functional heterocomplex with hsp90.
AB  - The hormone-binding domain of the glucocorticoid receptor must be bound to heat
      shock protein (hsp) 90 for it to have a high-affinity steroid-binding
      conformation. Cell-free assembly of a glucocorticoid receptor-hsp90 heterocomplex
      is brought about in reticulocyte lysate by a preformed protein-folding complex
      containing hsp90, hsp70, and other proteins [Hutchison, K.A., Dittmar, K. D., &
      Pratt, W.B. (1994) J. Biol. Chem. 269, 27894-27899]. In this "foldosome" system,
      hsp70 is required for assembly of the receptor-hsp90 complex and concomitant
      activation of steroid-binding activity [Hutchison, K.A., Dittmar, K.D., Czar,
      M.J., & Pratt, W.B. (1994) J. Biol. Chem. 269, 22157-22161]. All previous
      experiments involving cell-free assembly of both receptor-hsp90 and protein
      kinase-hsp90 heterocomplexes have been carried out with the protein-folding
      system in rabbit reticulocyte lysate. In this work, we show that concentrated
      lysates of receptor-free mouse (L cells) and insect (Sf9) cells and also a plant
      (wheat germ) lysate fold the immunopurified glucocorticoid receptor into a
      functional (i.e., steroid binding) heterocomplex with hsp90. Receptor
      heterocomplex formation in animal lysates and in the plant lysate are not
      identical in that the dynamics of complex assembly are different, but both
      systems produce a functional complex that binds steroid. Also, in contrast to
      animal and insect complexes, receptor-plant hsp90 complexes are not stabilized by
      molybdate. When added to the other lysate, purified plant and animal hsp90s show
      partial complementarity, in that a receptor-hsp90 complex is formed but the
      receptor is not converted to the steroid-binding conformation. When added to
      rabbit reticulocyte lysate that has been depleted of endogenous hsp70, purified
      wheat germ and mouse hsp70's are equally active in promoting both assembly of
      receptor-hsp90 heterocomplexes and conversion of receptor to the steroid-binding
      conformation. Thus, hsp70 from the plant kingdom has conserved the ability to
      interact functionally with chaperone proteins of the animal kingdom to cooperate
      in protein folding as evidenced by formation of a functional receptor-hsp90
      heterocomplex.

PMID- 8555228
TI  - Activation of calcineurin A subunit phosphatase activity by its calcium-binding B
      subunit.
AB  - The protein phosphatase activity of calcineurin (CaN) is activated through
      calcium binding to both calmodulin and the B subunit of CaN. The purpose of this
      study was to determine which domain(s) in the CaN B subunit is required for
      either binding to the CaN A subunit or for transducing the effects of B subunit
      Ca2+ binding to the stimulation of the CaN A subunit phosphatase activity. We
      have previously demonstrated that interaction of CaN B regulatory subunit with
      the CaN A catalytic subunit requires hydrophobic residues within the CaN A
      sequence 328-390 [Watanabe Y., Perrino, B.A., Chang, B.H., & Soderling, T.R.
      (1995) J. Biol. Chem. 270, 456-460]. In the present study, selected hydrophobic
      residues within the B subunit were mutated to Glu to Gln. CaN B subunit mutants
      BE-1 (Val115/Leu116 to Glu), BE-2 (Val156/157/168/169 to Glu), and BQ-2
      (Val156/157/168/169 to Gln) were expressed and purified. The three mutant B
      subunits bound 45Ca2+ normally. Mutants BE-2 and BQ-2 interacted with a GST
      fusion protein containing the B subunit binding domain of the CaN A subunit
      (residues 328-390), and they stimulated the phosphatase activity of the CaN A
      subunit in an in vitro reconstitution assay. Mutant BE-1 had a 3-fold reduced
      affinity for binding CaN A, and this mutant, even at saturating concentrations,
      gave very little stimulation of CaN A phosphatase activity. We conclude that
      residues Val115/Leu116 in the B subunit participate in high-affinity binding to
      the A subunit and are required for transducing the effects [i.e., decrease Km and
      increase Vmax; Perrino, B.A., Ng, L.Y., & Soderling, T.R. (1995) J. Biol. Chem.
      270, 340-346] of B subunit Ca2+ binding to stimulation of CaN A phosphatase
      activity.

PMID- 8555229
TI  - pH-dependent structural changes in the active site of p-hydroxybenzoate
      hydroxylase point to the importance of proton and water movements during
      catalysis.
AB  - Deprotonation of p-hydroxybenzoate to the phenolate and reprotonation of the
      hydroxylated dienone intermediate to form the product are essential steps in the
      reaction catalyzed by p-hydroxybenzoate hydroxylase (PHBH). The mechanism by
      which protons are transferred in these reactions is not obvious, because the
      substrate bound in the active site is isolated from solvent. Structure analyses
      of wild-type and mutant PHBH, with bound p-hydroxybenzoate or p-aminobenzoate,
      reveal a chain of proton donors and acceptors (the hydroxyl groups of Tyr201 and
      Tyr385, and two water molecules) that can connect the substrate 4-OH to His72, a
      surface residue. This chain could provide a pathway for proton transfer to and
      from the substrate. Using various combinations of pH and substrates, we show that
      in crystalline PHBH ionizable groups in the chain may rotate and change hydrogen
      bond orientation. Molecular dynamics simulations have been used to predict the
      preferred orientation of hydrogen bonds in the chain as a function of the
      ionization states of substrate and His72. The calculations suggest that changes
      in the ionization state of the substrate could be associated with changes in
      orientation of the hydrogen bonds in the chain. Transfer of water between the
      chain of proton donors and the solvent also appears to be an essential part of
      the mechanism that provides reversible transfer of protons during the
      hydroxylation reaction.

PMID- 8555230
TI  - Acetyltransfer precedes uridylyltransfer in the formation of UDP-N
      acetylglucosamine in separable active sites of the bifunctional GlmU protein of
      Escherichia coli.
AB  - The GlmU protein is a bifunctional enzyme with both acetyltransferase and
      uridylyltransferase (pyrophosphorylase) activities which catalyzes the
      transformation of glucosamine-1-P, UTP, and acetyl-CoA to UDP-N-acetylglucosamine
      [Mengin-Lecreulx, D., & van Heijenoort, J. (1994) J. Bacteriol. 176, 5788-5795],
      a fundamental precursor in bacterial peptidoglycan biosynthesis and the source of
      activated N-acetylglucosamine in lipopolysaccharide biosynthesis in Gram-negative
      bacteria. In the work described here, the GlmU protein and truncation variants of
      GlmU (N- and C-terminal) were purified and kinetically characterized for
      substrate specificity and reaction order. It was determined that the GlmU protein
      first catalyzed acetyltransfer followed by uridylyltransfer. The N-terminal
      portion of the enzyme was capable of only uridylyltransfer, and the C-terminus
      catalyzed only acetyltransfer. GlmU demonstrated a 12-fold kinetic preference
      (kcat/Km, 3.1 x 10(5) versus 2.5 x 10(4) L.mol-1.s-1) for acetyltransfer from
      acetyl-CoA to glucosamine-1-P as compared to UDP-glucosamine. No detectable
      uridylyltransfer from UTP to glucosamine-1-P was observed in the presence of
      GlmU; however, the enzyme was competent in catalyzing the formation of UDP-N
      acetylglucosamine from UTP and N-acetylglucosamine-1-P (kcat/Km 1.2 x 10(6) L.mol
      1.s-1). A two active site model for the GlmU protein was indicated both by domain
      dissection experiments and by assay of the bifunctional reaction. Kinetic studies
      demonstrated that a pre-steady-state lag in the production of UDP-N
      acetylglucosamine from acetyl-CoA, UTP, and glucosamine-1-P was due to the
      release and accumulation of steady-state levels of the intermediate N
      acetylglucosamine-1-P.

PMID- 8555231
TI  - Identification of two functionally different classes of exocellulases.
AB  - There are two classes of synergism in cellulase mixtures: synergism between
      endocellulases and exocellulases, and synergism between certain exocellulases.
      Exocellulases have been defined traditionally as releasing cellobiose from the
      nonreducing ends of cellulose, but this definition is inadequate to explain
      exo/exo synergism. Several recent reports indicate that some exocellulases are
      capable of hydrolyzing cellulose from the reducing end. The existence of two
      exocellulase classes with different specificities could provide an explanation
      for exo/exo synergism. In this paper, we report the substrate specificity of
      three Thermomonospora fusca (E3, E4, and E6) and two Trichoderma reesei (CBH I
      and CBH II) exocellulases on labeled cellooligosaccharides. We describe a new
      nonradioactive technique for determining substrate specificity, in which ion
      spray mass spectrometry was used to analyze the products of enzymatic digests of
      cellopentaose labeled with 18O at the reducing end. Exocellulase reactivity was
      also investigated on cellopentaose labeled at the nonreducing end with 14C, and
      cellooligosaccharides reduced with NaBH4. The distribution of label in the
      reaction products supports the existence of two functional classes of
      exocellulases. One class (containing CBH I, E4, and E6) preferentially cleaves
      cellooligosaccharides from the reducing end, while the other (containing E3 and
      CBH II) preferentially cleaves from the nonreducing end. This classification of
      exocellulases is consistent with exo/exo synergism experiments, and with
      published cellulase crystallographic data.

PMID- 8555232
TI  - Reactivity of a paramagnetic enzyme--CO adduct in acetyl-CoA synthesis and
      cleavage.
AB  - Partial reactions of acetyl-CoA cleavage by the Methanosarcina barkeri acetyl-CoA
      decarbonylase synthase enzyme complex were investigated by UV--visible and
      electron paramagnetic resonance (EPR) spectroscopy. Reaction of the enzyme
      complex with carbon monoxide generated an EPR-detectable adduct with principal g
      values of 2.089, 2.076, and 2.028, and line widths of 13.76, 16.65, and 5.41 G,
      respectively. The EPR signal intensity was dependent upon both enzyme and carbon
      monoxide concentration. A second signal with gav = 2.050 was generated by storage
      of the CO-exposed enzyme for 17 months at -70 degrees C. Reaction of the enzyme
      complex with low levels of CO caused reduction of the enzyme complex, but did not
      result in immediate formation of the NiFeC signal (designated NiFeC based on
      isotopic substitution studies carried out by others in analogous systems from
      Clostridium thermoaceticum and Methanosarcina thermophila). Further addition of
      CO generated the NiFeC signal, and the signal amplitude then increased
      progressively with increasing CO concentration. UV-visible spectra showed that
      enzyme Fe-S and corrinoid centers were already fully reduced at levels of CO
      significantly lower than needed for maximal EPR signal intensity. This result
      indicated that the EPR signal is formed by reaction of the reduced enzyme with CO
      (or a reduced one-carbon species), rather than with a one-carbon unit at the
      oxidation level of CO2. Addition of coenzyme A, acetyl-CoA, or
      tetrahydrosarcinapterin had no effect on the EPR signal. In contrast, addition of
      N5-methyltetrahydrosarcinapterin (CH3-H4SPt) abolished the EPR signal. EPR
      spectra recorded at 20-21 K revealed that reaction with CH3-H4SPt affects only
      the enzyme NiFeC signal, and does not influence other EPR-detectable Fe-S
      center(s). The results suggest that the enzyme--CO adduct reacts with CH3-H4SPt
      to form an EPR-silent enzyme-acetyl species. Preincubation of the enzyme complex
      with CO and CH3-H4SPt, both of which were required, produced an approximately 44
      fold increase in the turnover rate of acetyl-CoA synthesis. The relevance of
      these findings to mechanisms involving possible reductive methylation of the
      enzyme and/or acetyl-enzyme formation is discussed.

PMID- 8555233
TI  - Aminoacyl-tRNA synthetases optimize both cognate tRNA recognition and
      discrimination against noncognate tRNAs.
AB  - Specific protein--nucleic acid interactions are usually the product of sequence
      dependent hydrogen bonding. However, in the crystal structure of Escherichia coli
      glutaminyl-tRNA synthetase (GlnRS) in complex with tRNAGln, leucine 136 (Leu136)
      stabilizes the disruption of the weak first (U1-A72) base pair in tRNAGln by
      stacking between A72 and G2. We have demonstrated, by a combined in vivo and in
      vitro mutational analysis, that Leu136 is important for tRNA specificity despite
      making no hydrogen bonds with tRNAGln. Both more (L136F) and less (L136V, L136M,
      L136A, and L136T) mischarging mutants of GlnRS have been identified. GlnRS(L136F)
      is more mischarging and less specific than wild-type GlnRS in vivo, due not to an
      increased affinity for the noncognate tRNAs but to a decreased affinity for
      tRNAGln. Also, unlike other mischarging mutants of GlnRS that have been
      characterized, it does not exhibit generally relaxed tRNA specificity in vivo and
      mischarges only a subset of the tRNAs tested. A possible sequence preference for
      a Py1-Pu72/Pu2-Py71 combination is suggested. The L136A/M/T/V mutants are the
      first GlnRS variants, including wild-type, expressed on pBR322 which no longer
      mischarge tyrT(UAG) in vivo. We have shown that, while the L136A mutant is less
      mischarging than wild-type both in vivo and in vitro, it is not more specific as
      it also exhibits reduced affinity for its cognate glutamine tRNA. On the basis of
      these results, we suggest that the aminoacyl-tRNA synthetases have evolved to
      balance cognate tRNA recognition and discrimination against noncognate tRNAs.

PMID- 8555234
TI  - Evidence that specificity of microhelix charging by a class I tRNA synthetase
      occurs in the transition state of catalysis.
AB  - Determinants for the identities of tRNAs are located in the acceptor stem and,
      commonly, in the anticodon as well. Although the anticodon is an important
      determinant for the identity of methionine tRNA, RNA microhelices whose sequences
      are based on the acceptor stem alone can be aminoacylated by the class I
      methionyl-tRNA synthetase. We show here that specific nucleotide substitutions in
      a microhelix significantly reduced its rate of aminoacylation. In contrast,
      affinity coelectrophoresis analysis showed that microhelix binding to the enzyme
      was not significantly affected by the same substitutions. These and additional
      experiments and considerations imply that specific determinants for microhelix
      aminoacylation are needed for orientation of the acceptor stem in the transition
      state of catalysis rather than for enhanced binding interactions. The effect of
      linking together acceptor stem interactions with those in the anticodon, as
      occurs in the whole tRNA molecule, was also evaluated. This analysis showed that
      linkage results in some of the favorable acceptor stem and anticodon interactions
      being used to offset the free energy cost of straining the structure of the
      enzyme-tRNA complex.

PMID- 8555235
TI  - Binding of the antitumor drug nogalamycin to bulged DNA structures.
AB  - Defects in DNA, e.g., unpaired/bulged nucleotides, are repaired by specific
      repair enzymes. Understanding the dynamics and structure of DNA defects is
      important. Two DNA heptamers, CTb-GTACG and CGTACTbG, each containing a bulged T
      nucleotide embedded in the CpG step, have been studied by NMR. Both duplexes are
      significantly destabilized, and the bulged T remains intrahelical. Binding of the
      anthracycline antitumor antibiotic nogalamycin (Ng) to these two heptamers
      stabilizes the duplex structure. The solution structures of the 2:1 complexes of
      Ng-d(CTbGTACG) and Ng-d(CGTACTbG) have been determined by the NOE-restrained
      refinement procedure. In both structures the elongated aglycon of Ng is
      intercalated between base pairs, and the nogalose and aminoglucose lie in the
      minor and major grooves, respectively. The bulged T behaves differently upon the
      binding of Ng. In Ng-CTbGTACG wobble G6:Tb base pairs are formed, leaving two
      dangling 5'-C1 nucleotides; whereas in Ng-CGTACTbG weak C1:Tb base pairs are
      formed, leaving two dangling 3'-G6 nucleotides. Thus Ng induces the bulged T and
      the opposing base in the duplex to stack on the aglycon and causes the base next
      to Tb to unpair, mimicking a "frame-shift". Such structural rearrangement of a
      bulged DNA site due to the binding of an intercalator drug may perturb the
      recognition of DNA defects by repair enzymes or may cause mutation during
      replication.

PMID- 8555236
TI  - N,N-dimethylsphingosine inhibition of sphingosine kinase and sphingosine 1
      phosphate activity in human platelets.
AB  - Potential sphingosine (Sph) metabolites include phosphorylated, N-acylated, and N
      methylated derivatives. Phosphorylated Sph, i.e., sphingosine 1-phosphate (Sph-1
      P), may act as an autocrine stimulator of blood platelets, as it is abundantly
      stored in platelets and released extracellularly and its exogenous addition
      induces platelet activation. In this study, we evaluated Sph-1-P formation and
      its effects in human platelets in the presence of other Sph metabolites. On
      addition of [3H]Sph to intact platelets, the label was rapidly converted to Sph-1
      P. This conversion into [3H]Sph-1-P was inhibited by N,N-dimethylsphingosine
      (DMS) in a dose-dependent manner, but not by other structurally related Sph
      derivatives, including ceramide. The inhibition of Sph-1-P formation by DMS was
      reproduced using a cell-free system (Sph kinase obtained from platelet cytosolic
      fractions) and much stronger than that by DL-threo-dihydrosphingosine, which had
      been considered to be the strongest inhibitor of Sph kinase. Administration of
      DMS to intact platelets resulted in a decrease in Sph-1-P mass and an increase in
      Sph mass. Furthermore, DMS inhibited the release of Sph-1-P from platelets
      stimulated with 12-O-tetradecanoylphorbol 13-acetate and inhibited platelet
      aggregation induced by exogenous addition of Sph-1-P. Collectively, our results
      indicate that DMS is useful as a Sph kinase inhibitor and that Sph-1-P actions as
      an autocrine stimulator of platelets are inhibited by DMS.

PMID- 8555237
TI  - Twofold symmetry of human fibrinogen proved at the beta chain distal domains by
      monoclonal-immunoelectron microscopy and image analysis.
AB  - Using a murine antibody (F7) specific for the C-terminal domain of the beta chain
      of human fibrinogen combined with electron microscopy and image analysis, we show
      unequivocally that the epitopes for F7 are at the distal nodules of fibrinogen,
      equidistant from the center of the molecule and arranged not colinearly with the
      long axis of the molecule but at opposite sides of it, i.e., following twofold
      symmetry. Thus, given the monoclonality of the immunochemical probe used and the
      dimeric nature of the fibrinogen molecule, we can conclude that the distal
      domains of the two beta chains are arranged in the same manner as these epitopes
      and, therefore, that the fibrinogen molecule has twofold symmetry. This symmetry
      pattern found here for F7 is the same as that found recently for the platelet
      fibrinogen receptor binding sites [Weisel, J. W., Nagaswami, C., Vilaire, G., &
      Bennett, J. S. (1992) J. Biol. Chem. 23, 16637-16643], located almost certainly
      at the C-terminal end of the gamma chains, and gives further support to the most
      accurate model of fibrinogen available so far. We discuss the consequences of
      this symmetry pattern and of the molecular rigidity of fibrinogen in the actual
      models of fibrin polymerization and platelet aggregation and adhesion.

PMID- 8555238
TI  - Activation of Sulfolobus solfataricus alcohol dehydrogenase by modification of
      cysteine residue 38 with iodoacetic acid.
AB  - Reaction of thermostable NAD(+)-dependent alcohol dehydrogenase from Sulfolobus
      solfataricus with iodoacetate at pH 9.0 and 37 degrees C significantly increases
      the oxidation rate of aliphatic and aromatic alcohols and decreases the reduction
      rate of aromatic aldehydes. The archaeal ADH is chemically modified and activated
      in a Michaelis-Menten-type reaction, where one molecule of the reagent binds per
      active site. NAD+ in micromolar concentration protects the enzyme against the
      inhibitor in an uncompetitive manner, while imidazole significantly increases the
      extent of the activation. Carboxymethylation selectively modifies one out of five
      cysteine residues per subunit, namely, Cys 38, located in the catalytic site, as
      determined by peptide and sequence analysis, and enhances by up to 25-fold the
      oxidation rate of benzyl alcohol. Carboxymethylated SsADH is less thermostable
      and shows a temperature optimum 30 degrees C lower than that of the native
      enzyme. The carboxymethylated enzyme exhibits a lower affinity toward the
      oxidized and reduced coenzyme. The dissociation constants for NAD+ and NADH
      determined at 25 degrees C and pH 8.8 are 60- and 200-fold higher, respectively,
      compared to the native enzyme. The significant isotope effect in alcohol
      oxidation suggests that hydride transfer partially limits the turnover rate of
      the reaction catalyzed by the modified enzyme, whereas the rate-limiting step for
      the native enzyme is NADH dissociation. Carboxymethylated enzyme probably gives
      higher maximum velocities of oxidation because of the faster dissociation of the
      modified enzyme-coenzyme complex.

PMID- 8555239
TI  - A mechanistic framework for the second step of splicing catalyzed by the
      Tetrahymena ribozyme.
AB  - A simple model system is described which mimics the second step of splicing and
      reverse cyclization reactions of the self-splicing intron from Tetrahymena
      thermophila. This model is based on the L-21 Sca I catalyzed ligation reaction
      between exogenously added oligomers: cucu + UCGa L-21 Sca I cucua + UCG. Steady
      state kinetics for the forward and reverse direction were measured at 15 degrees
      C to find oligonucleotides that exhibit Michaelis-Menten behavior with acceptable
      KMS. CUCU and UCGA fit both criteria and were chosen for further studies. Steady
      state kinetics reveal a lag that appears to be an RNA folding step that is
      eliminated by preincubation of the ribozyme with 2 mM and higher [Mg2+] and by
      UCGA. At constant ionic strength, the Mg2+ dependence of steady-state rates
      exhibits a sharp maximum near 5 mM Mg2+. Pre-steady-state and steady-state
      kinetics, along with active-site titrations, explain the Mg2+ profile: the rate
      of reaction up to and including chemistry increases with Mg2+ concentration,
      while the fraction of active ribozyme and the rate of postchemistry steps
      decrease with Mg2+ concentration. The rate-limiting step at 5 mM Mg2+ for the
      reaction mimicking the second step of splicing is either chemistry or a
      conformational change before chemistry involving ribozyme bound with substrates.
      The rate-limiting step at 50 mM Mg2+ appears to be a postchemistry conformational
      change of the ribozyme or product release. At 50 mM Mg2+, single-turnover
      experiments support ordered binding of substrates with 5'-exon mimic binding
      before 3'-splice site mimic. Moreover, the 3'-splice site mimic binds and reacts
      in the presence of 5'-exon mimics predocked into the catalytic core. Results also
      indicate that Mg2+ ions associate with the ribozyme upon docking.

PMID- 8555240
TI  - 3'- and 5'-strand cleavage reactions catalyzed by the Fpg protein from
      Escherichia coli occur via successive beta- and delta-elimination mechanisms,
      respectively.
AB  - The Fpg protein from Escherichia coli is a multifunctional protein that excises
      damaged purine bases from DNA to generate aldehydic abasic sites and then
      catalyzes the successive cleavage of the phosphodiester bonds first on the 3'
      side and then on the 5'-side of the abasic site to generate 5'- and 3'-phosphate
      ends, respectively, thereby excising the deoxyribose residue. The mechanisms of
      the 3'- and 5'-strand cleavage reactions have been studied by nuclear magnetic
      resonance spectroscopy (NMR) and gas chromatography-mass spectrometry (GC-MS).
      The 3'-strand cleavage reaction is a beta-elimination reaction in which the 2'
      hydrogen is abstracted and the 3'-phosphate is eliminated. The 5'-strand cleavage
      reaction is a delta-elimination reaction in which the 4'-hydrogen is abstracted
      and the 5'-phosphate is eliminated. Two types of experiments were performed to
      establish the occurrence of the sequential elimination reactions. First, when the
      reaction was performed in H2(18)O, 31P NMR demonstrated that neither phosphate
      group contained 18O. Second, the five-carbon product derived from the deoxyribose
      residue was stabilized by reduction with NaBH4 and characterized by GC-MS. The
      mass spectrum of the reduced product was identical to that of authentic 4-oxo-2
      pentenal, the tautomerized product of successive beta- and delta-elimination
      reactions.

PMID- 8555241
TI  - Control of arachidonate levels within inflammatory cells.

PMID- 8555242
TI  - The molecular structure of apolipoprotein A-II modulates the capacity of HDL to
      promote cell cholesterol efflux.
AB  - The influence of apolipoprotein A-II (apoA-II) molecular structure on the
      capacity of high density lipoproteins (HDL) to promote cellular cholesterol
      efflux was investigated in cultured mouse peritoneal macrophages (MPM).
      Conversion by reduction and carboxamidomethylation of the naturally occurring
      dimeric apoA-II to its monomeric form in both native or reconstituted HDL did not
      change apolipoprotein secondary structure and lipoprotein size/composition. All
      particles containing monomeric apoA-II, i.e., native HDL3 or reconstituted HDL
      with or without apoA-I, showed a higher ability to promote cholesterol efflux
      originating from plasma membrane and intracellular stores, compared to particles
      containing dimeric apoA-II. These findings indicate that apolipoprotein molecular
      structure is a major determinant of HDL capacity to promote cholesterol efflux
      from cells.

PMID- 8555243
TI  - beta-carotene as a high-potency antioxidant to prevent the formation of
      phospholipid hydroperoxides in red blood cells of mice.
AB  - In order to investigate the antioxidant effect of beta-carotene in vivo,
      phospholipid hydroperoxides and beta-carotene isomers in red blood cells (RBC),
      plasma and tissue organelles were quantitatively measured after the oral
      administration of beta-carotene (94.8% all-trans-beta-carotene) to mice. Three
      groups of 24 mice each were fed for 1 week on a semisynthetic diet supplemented
      with either 0.6% or 3.0% beta-carotene/diet or maintained on a control (beta
      carotene-unsupplemented) diet. The RBC phospholipid hydroperoxides showed a
      significant decrease followed by an increase of beta-carotene intakes; i.e., 201,
      16 and 4 pmol of phosphatidylcholine hydroperoxide/ml packed RBC, and 108, 22 and
      8 pmol of phosphatidylethanolamine hydroperoxide/ml packed RBC, in the mice given
      the control diet, 0.6% carotene diet and 3.0% carotene diet, respectively. The
      RBC beta-carotene increased from 14 to 43 pmol/ml packed RBC as followed by the
      increase of beta-carotene intakes. Such a potent antioxidant effect of beta
      carotene as observed in RBC was not confirmed in the plasma, liver or lungs,
      although their beta-carotene contents increased. The beta-carotene ingestion
      increased the all-trans-beta-carotene and retinol contents in RBC, plasma, liver
      and lungs, but the alpha-tocopherol content decreased. In the beta-carotene
      supplemented (6 g and 30 g/kg diet) mice, cis-beta-carotene content was
      relatively higher in the RBC (25-35% of total beta-carotene) than that in the
      plasma, liver and lungs. The present findings indicate that not only does beta
      carotene act as a potent antioxidant in vivo but also its antioxidant effect is
      very specific in the RBC phospholipid bilayers rather than in the plasma and
      other tissue organelles.

PMID- 8555244
TI  - Characterization of the Fad12 mutant of Synechocystis that is defective in delta
      12 acyl-lipid desaturase activity.
AB  - The Fad12 mutant of Synechocystis sp. PCC 6803 has a defect in the desA gene for
      delta 12 acyl-lipid desaturase. We identified a change in the nucleotide sequence
      of the structural gene for the desaturase, in which a leucine codon has been
      converted to a stop codon. Western blot analysis revealed that the delta 12 acyl
      lipid desaturase was localized in both plasma membranes and thylakoid membranes
      of wild-type cells but was absent from both types of membrane in Fad12 cells.
      These findings suggest that the desaturation of fatty acids takes place in both
      types of membrane in Synechocystis sp. PCC 6803. The mutation in the delta 12
      desaturase did not affect the lipid composition of thylakoid and plasma
      membranes, but it changed the fatty acid composition of lipids in similar ways in
      both types of membrane.

PMID- 8555245
TI  - Prostaglandin synthase 2.

PMID- 8555246
TI  - Regulation of glycolipid sulfotransferase by tyrosine kinases in human renal
      cancer cells.
AB  - Glycolipid sulfotransferase activity in a human renal cancer cell line, SMKT-R3,
      is enhanced by the action of growth factors such as EGF, TGF-alpha and HGF, whose
      receptors possess tyrosine kinase domains. We investigated whether tyrosine
      kinases are involved in the regulation of the sulfotransferase in the cells by
      using specific tyrosine kinase inhibitors. Genistein and tyrphostin 51 not only
      cancelled the enhancement of the sulfotransferase by EGF but also reduced the
      enzyme level to a point much lower than that seen in non-treated cells, whereas
      they did not affect the sulfotransferase activity in vitro. The activity-reducing
      effects of genistein were dose- and time-dependent. Genistein also inhibited the
      cell growth of SMKT-R3 cells. Western blotting using anti-phosphotyrosine
      monoclonal antibody revealed a tyrosine-phosphorylated protein with an apparent
      molecular mass of 116 kDa in the non-treated cells. The EGF receptor was tyrosine
      phosphorylated by the addition of EGF. The phosphorylations of the 116 kDa
      protein and EGF receptor were attenuated by co-incubation with genistein. These
      results indicate that tyrosine kinases including the EGF receptor are involved in
      the growth of SMKT-R3 cells and in the regulatory mechanisms of glycolipid
      sulfotransferase in the cells.

PMID- 8555247
TI  - Alteration of glycerolipid and sphingolipid-derived second messenger kinetics in
      ras transformed 3T3 cells.
AB  - The effect of ras transformation (rasB fibroblasts) on basal and serum-stimulated
      diacylglycerol (DAG) composition and mass was examined over time with respect to
      changes in membrane phospholipid composition and ceramide mass. RasB cells vs.
      nontransformed control cells (rasD and NR6) had chronically elevated DAG levels
      (up to 240 min) following serum stimulation, indicating a defect in the recovery
      phase of the intracellular DAG pulse. Ras transformation also had a dramatic
      effect on DAG composition. Molecular species analysis revealed that DAG from
      unstimulated rasB cells was enriched in the delta 9 desaturase fatty acyl species
      (monoenoate 18:1(n - 7) and 18:1(n - 9)), and depleted in arachidonic acid
      (20:4(n - 6)). With the exception of glycerophosphoinositol (GPI), DAG remodeling
      paralleled the compositional alterations in individual phospholipid classes.
      Importantly, ras transformation altered the fatty acyl composition of
      sphingomyelin, a precursor to the ceramide second messenger. With the addition of
      serum, control cells (rasD) had a progressive increase in ceramide mass with
      levels approximately 5-fold higher by 240 min. In contrast, ceramide levels did
      not increase in rasB cells at either 4 or 240 min. These results demonstrate that
      ras-oncogene, in addition to its effects on DAG metabolism, can also abolish the
      cellular increase in ceramide mass in response to serum stimulation. Since DAG
      and ceramide may have opposing biological functions, the prolonged elevation of
      DAG and the suppression of ceramide levels would be consistent with an enhanced
      proliferative capacity.

PMID- 8555248
TI  - Thioesterase and protein deacylase activities of porcine pancreatic phospholipase
      A2.
AB  - The thioesterase activity of porcine pancreatic phospholipase A2 has been
      investigated with non-phospholipid substrates. The acyl-CoA hydrolase activity
      towards acyl-CoA derivatives is specific for long chain fatty acids (14 C, 16 C)
      but is unable to hydrolyze short chain acyl-CoA compounds (below 8 C). The same
      enzyme also shows protein deacylase activity liberating [3H]palmitic acid from
      [3H]palmitoyl-acyl carrier protein.

PMID- 8555249
TI  - Oxidative stress mediates synthesis of cytosolic phospholipase A2 after UVB
      injury.
AB  - UVB irradiation has previously been shown to significantly increase phospholipase
      activity and prostaglandin synthesis. Because UVB irradiation is a potent
      oxidative stress, the role of active oxygen species in regulating UV-induced
      cPLA2 synthesis and phosphorylation was examined. In the present study,
      irradiation produced a 3-fold increase in synthesis within 6 h following
      irradiation. Phosphorylation of cPLA2 was also increased to a similar extent. UVB
      induced synthesis and phosphorylation of cPLA2 could be inhibited by pretreatment
      with the antioxidants 2,2,5,7,8-pentamethyl-6-hydroxychromane (50 microM) or N
      acetylcysteine (10 mM). Treatment of unirradiated cultures with the potent
      oxidant tert-butyl hydroperoxide (500 microM) also increased cPLA2 synthesis and
      phosphorylation, suggesting that oxidative injury is an important regulator of
      cPLA2 synthesis. Increased synthesis of cPLA2 correlated well with increased
      [3H]arachidonic acid release, PGE2 synthesis and lipid peroxidation in epidermis
      after oxidant or UVB treatment. The results indicate that UVB-induced
      upregulation of cPLA2 synthesis is mediated by UVB-induced formation of free
      radicals.

PMID- 8555250
TI  - Inhibitory effects of alkyl gallate and its derivatives on fatty acid
      desaturation.
AB  - Alkyl gallate, which is known as an antioxidant, intensively inhibited delta 5
      and delta 6 desaturation in both rat liver microsomes and an arachidonic acid
      producing fungus Mortierella alpina 1S-4. The rat liver microsomal delta 5 and
      delta 6 desaturases were inhibited by gallic acid esterified with alcohols with
      various numbers of carbons, suggesting that the necessary structure in an
      esterified alcohol for the inhibition is not so strict. Among the three hydroxy
      groups in gallic acid, the m-hydroxy group was shown to be the necessary
      structure. Kinetic analyses revealed that propyl gallate is a noncompetitive
      inhibitor of delta 5 desaturase (Ki = 2.6.10(-5)M) and delta 6 desaturase (Ki =
      1.7.10(-4) M). These data indicate that alkyl gallate is a new type of desaturase
      inhibitor and different from known natural inhibitors, i.e., sesamin and
      curcumin.

PMID- 8555251
TI  - Developmental regulation of phospholipid secretion by fetal type II pneumocytes.
AB  - Surfactant sufficiency is dependent upon adequate synthesis and secretion of
      surfactant by the type II alveolar epithelium. Our laboratory has previously
      shown that basal secretion of surfactant phospholipid by differentiated fetal
      type II cells is lower than the basal secretion by adult cells. The purposes of
      this study were to determine if undifferentiated fetal type II cells can secrete
      phosphatidylcholine, to determine if terbutaline, a beta-adrenergic agonist,
      stimulates secretion of surfactant phospholipids by undifferentiated fetal cells
      and to examine the effects of differentiation on secretion of surfactant
      phospholipids by fetal cells. Constitutive (basal) secretion of
      phosphatidylcholine increased linearly as a function of time in both
      undifferentiated and differentiated cells, but the rate of secretion was greater
      in differentiated cells than the rate of secretion in undifferentiated cells.
      Terbutaline caused a concentration-dependent increase in secretion in both
      undifferentiated and differentiated cells. Maximal effective concentration and
      EC50 were similar for undifferentiated (10(-6) M, 0.2 microM) and differentiated
      (10(-5) M, 0.3 microM) cells. The relative stimulation of secretion above control
      values was greater for undifferentiated cells. The kinetics of terbutaline
      stimulation varied significantly with cellular differentiation. Terbutaline
      resulted in 230% stimulation of secretion in undifferentiated cells at 30 min
      followed by a decline in the response to terbutaline at 60 to 120 min. In
      contrast, terbutaline stimulated secretion by differentiated cells showed a
      sustained linear increase from 0 to 120 min. This regulation of stimulated
      secretion is not present in undifferentiated cells. We conclude that
      undifferentiated type II cells are capable of the secretion of
      phosphatidylcholine and that terbutaline stimulates secretion by undifferentiated
      cells. Furthermore, basal secretion increases as a function of differentiation of
      type II cells and the regulation of stimulated secretion seen in differentiated
      cells is not developed in undifferentiated cells. The developmental regulation of
      the secretion of surfactant is complex and probably involves both excitatory as
      well as inhibitory mechanisms which develop at different stages of
      differentiation of the type II cell.

PMID- 8555252
TI  - Peroxidative oxidation of leuco-dichlorofluorescein by prostaglandin H synthase
      in prostaglandin biosynthesis from polyunsaturated fatty acids.
AB  - Prostaglandin H synthase can oxidize arachidonic acid with leuco
      dichlorofluorescein as reducing cosubstrate. Addition of 0.5 mM phenol increases
      the oxidation of leuco-dichlorofluorescein to dichlorofluorescein 5-fold,
      probably by acting as a cyclic intermediate in the oxidation. Tetramethyl-p
      phenylenediamine is also oxidized as cosubstrate. Its oxidation is not influenced
      by phenol. A stoichiometry of close to one mole of tetramethyl-p-phenylenediamine
      or leuco-dichlorofluorescein consumed per mole of arachidonic acid was found in
      the initial phase of the reaction. In the presence of phenol + leuco
      dichlorofluorescein, the oxidation rate of arachidonic acid is about 40% lower
      than with phenol alone as cosubstrate. Since dichlorofluorescein has a molar
      extinction coefficient of 91 . 10(3) at 502 nm, the oxidation of less than 1
      microM leuco-dichlorofluorescein can be detected spectrophotometrically. The rate
      of extinction change with leuco-dichlorofluorescein (at 502 nm) is about 4-fold
      more rapid than with tetramethyl-p-phenylenediamine (at 611 nm). With this
      spectrophotometric assay we have confirmed that arachidonic acid, linolenic acid,
      adrenic acid, gamma-linolenic acid, eicosapentaenoic acid, are substrates for
      prostaglandin H synthase with decreasing reaction rates in the mentioned order.
      The same order of reaction rates were found when oxygen consumption was measured.
      The assay also shows that docosahexaenoic acid is substrate for the enzyme. The
      reaction rate of the enzyme evidently is decreased both by a n-3 double bond and
      by deviation from a 20 carbon chain length of the fatty acid substrate.

PMID- 8555253
TI  - The pattern of apolipoprotein B100 containing lipoprotein subclasses produced by
      the isolated visceral rat yolk sac depends on developmental stage and fatty acid
      availability.
AB  - Explants of visceral rat yolk sacs from gestational days 16, 18 and 22 were used
      for studying developmental changes of secretion and density distribution of
      lipoproteins, particularly of those containing apoB. Moreover, the influence of
      fatty acid supply on the amount and density distribution of secreted
      apolipoproteins was studied on day 18 of gestation. Active lipoprotein production
      was observed in yolk sacs taken on days 16 and 18 of gestation. It declined
      considerably on day 22 of gestation in parallel with the production of total
      protein, triacylglycerols and cholesterol. On all gestational days, apoB floated
      mainly in the LDL range ( > or = 70%) with differences in the distribution
      pattern of LDL subclasses. The lowest density of secreted LDL was found on day 18
      of gestation (peak at d = 1.025 g/ml) followed by day 16 (peak at d = 1.035 g/ml)
      and day 22 of gestation (peak at d = 1.045 g/ml). ApoAIV, apoE and apoAI floated
      exclusively in the HDL range with a peak at d = 1.089 g/ml independently of the
      gestational day. After incubation of yolk sacs from the 18th day of gestation
      with 0.4 mM or 0.8 mM oleate, the density of secreted apoB containing particles
      was decreased (peaks in the VLDL and IDL density range), whereas palmitate in the
      same concentrations caused a redistribution of secreted apoB toward higher
      densities (peaks at d > or = 1.032 g/ml). Taken together, the data provide
      evidence that the density of LDL subclasses produced by isolated yolk sacs
      between days 16 and 22 of gestation depended on the gestational stage. Moreover,
      addition of unsaturated or saturated fatty acids to the organ culture differently
      affected the secretory rate and the density of lipoproteins delivered by yolk
      sacs on day 18 of gestation.

PMID- 8555254
TI  - Lack of correlation between ACAT mRNA expression and cholesterol esterification
      in primary liver cells.
AB  - A partial rabbit cDNA clone (14b) for ACAT has been characterized and used to
      demonstrate that hepatic and aortic ACAT mRNA14b abundance increased 2-3-fold in
      rabbits receiving a high fat/high cholesterol-diet compared to chow fed animals
      (Pape et al. (1995) J. Lipid Res. 36, 823-838). Because of those data we
      hypothesized that increased hepatic cholesteryl ester mass and synthesis rates in
      rabbit liver cells are associated with an increase in ACAT mRNA14b levels. To
      test this hypothesis we altered cellular cholesteryl ester mass and synthesis
      rates in primary parenchymal and nonparenchymal cells using various extracellular
      agents and measured the accumulated mass of ACAT mRNA14b. Parenchymal cells
      incubated with rabbit beta VLDL or mevalonolactone displayed a 6-10-fold increase
      in cellular cholesteryl ester mass over a three day treatment with no significant
      changes in cellular free cholesterol, triacylglycerols, or ACAT mRNA14b levels;
      HMG CoA reductase and LDL receptor mRNA mass decreased initially as a result of
      cholesteryl ester loading. Treatment of parenchymal cells with CI-976, an ACAT
      inhibitor, showed a marked reduction in cholesteryl ester synthetic rate compared
      to beta VLDL controls but displayed no change in ACAT mRNA14b levels. A mixed
      population of rabbit hepatic nonparenchymal cells was incubated with beta VLDL
      for 24 h in culture which resulted in a 6-fold increase in cellular cholesteryl
      ester mass; there was no change in ACAT mRNA14b levels. In an in vivo study,
      rabbits consuming a high fat/high cholesterol-diet for three weeks showed a 10
      fold increase in hepatic cholesteryl ester with no significant changes in ACAT
      mRNA14b levels. Together these data indicate that rabbit liver cellular
      cholesteryl ester mass increases of up to 10-fold are not correlated with ACAT
      mRNA14b changes. Thus, hepatic ACAT mRNA14b expression and cellular cholesterol
      esterification do not appear to be coordinately regulated at this level of
      cholesteryl ester loading.

PMID- 8555255
TI  - Low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A
      reductase mRNA levels are coordinately reduced in human renal cell carcinoma.
AB  - The current investigation aimed to determine if the gene expression of important
      structures in cholesterol metabolism is altered in a solid human tumor. For this
      purpose we determined low density lipoprotein (LDL) receptor and 3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMG-CoA reductase) transcript levels and
      total tissue cholesterol in both tumors and normal kidney tissue in a series of
      samples from 29 patients with renal cell carcinoma. (RCC). LDL-receptor- and HMG
      CoA reductase mRNA levels were reduced in tumor tissue as compared with normal
      kidney tissue (by 29%, P < 0.03, and 31%, P < 0.001 respectively). The LDL
      receptor mRNA levels correlated significantly to the mRNA levels for HMG-CoA
      reductase in tumors (P < 0.0001) and normal kidney tissue (P < 0.03). The total
      tissue cholesterol levels in tumors were 5-fold elevated (P < 0.0001) as compared
      to normal kidney. We conclude that the mRNA levels for LDL-receptor and HMG-CoA
      reductase are regulated in parallel in human RCC and in normal kidney, and that
      these mRNA are generally reduced in human RCC. The data indicate that the
      accumulation of cholesterol in RCC may not be due to increased LDL receptor
      expression or de novo synthesis of cholesterol.

PMID- 8555256
TI  - Glucosylceramides of oat root plasma membranes--physicochemical behaviour in
      natural and in model systems.
AB  - Glucosylceramides from oat root plasma membranes have been characterized using
      HPLC-particle beam-mass spectrometry, differential scanning calorimetry, low
      angle X-ray diffraction and surface balance technique. 24:1-OH was dominating
      fatty acid (90%) together with 24:0-OH and 22:1-OH. The sphingosine base was
      sphingadienine isomers and the monosaccharide alpha and beta glucose.
      Differential scanning calorimetry of an aqueous dispersion of glucosylceramide
      revealed during heating an endothermic gel-liquid crystalline transition with
      double peaks at 47 degrees and 51 degrees C, the lowest known for naturally
      occurring glucosylceramides. A cooling scan after the endothermic gel-liquid
      transition showed one exotherm at 15 degrees C and if this was followed by
      another heating scan a large exotherm appeared with a peak at 18 degrees C.
      During the second heating the matrix was hydrated and the exotherm at 18 degrees
      C reflects then the transition between the supercooled metastable gel phase and
      the corresponding hydrated form. The calorimetric data indicate a lamellar phase
      which during the cooling scan appeared as an supercooled liquid crystalline
      phase. Low angle X-ray diffraction confirmed these calorimetric data. The surface
      pressure-area-curves of pure oat glucosylceramides were more expanded than those
      of bovine origin. Mixtures of oat glucosylceramides and phosphatidylcholine
      species similar to those present in oat root plasma membranes showed molecular
      miscibility but no interaction.

PMID- 8555257
TI  - Oxidation of high density lipoproteins: characterization and effects on
      cholesterol efflux from J774 macrophages.
AB  - Oxidative modification of high density lipoproteins (HDL) may alter their
      capacity to mediate cellular cholesterol efflux. We studied the kinetics of
      copper-mediated oxidation of HDL and cholesterol efflux mediated by unmodified
      and oxidized HDL (oxHDL). Oxidation was measured by increases in absorbance at
      234 nm (delta A234), production of thiobarbituric acid reactive substances
      (TBARS) and loss of trinitrobenzene sulfonic acid reactivity. Oxidation was
      dependent on copper concentration and showed a lag phase and propagation phase.
      Efflux of cholesterol from J774 macrophages measured by appearance of cellular
      [3H]cholesterol in the medium was lower by 16% after 4 h and 36% after 24 h with
      oxHDL compared to HDL. OxHDL-mediated efflux was also lower by 27% to 37% at
      lipoprotein concentrations of 10 to 200 micrograms protein/ml. Cholesterol efflux
      correlated negatively with TBARS production (r = -0.97, P < 0.003) and delta A234
      (r = -0.77, P < 0.080). There was no difference in efflux mediated by apoproteins
      prepared from HDL and oxHDL. Efflux measured by change in cholesterol mass in
      medium was 78% lower with oxHDL. Inhibition of oxidation with butylated
      hydroxytoluene maintained the capacity of HDL to stimulate efflux. These results
      suggest that oxidation of HDL may impair its protective role against
      atherosclerosis.

PMID- 8555258
TI  - Cholesterol lowering action of HOE 402 in the normolipidemic and
      hypercholesterolemic golden Syrian hamster.
AB  - The potent hypolipidemic activity of HOE 402 (4-amino-2-(4, 4-dimethyl-2-oxo-1
      imidazolidinyl)pyrimidine-5-N-(trifluoromethyl-phenyl ) carboxamide
      monohydrochloride), which was previously demonstrated in rat and rabbit, was
      investigated in noncholesterol and cholesterol fed male hamsters. In
      normolipidemic hamsters fed a low cholesterol chow diet containing 0.10% or 0.15%
      HOE 402 for 3 weeks, the plasma total cholesterol level fell by 13% and 20%
      respectively, but no effect on hepatic total cholesterol content was detected.
      Hepatic sterol synthesis was increased 3-fold in hamsters fed 0.15% HOE 402. In
      hamsters fed a chow diet containing 0.25% cholesterol for 3 weeks, the plasma
      cholesterol level increased to 226 mg/dl (compared to 123 mg/dl in their chow fed
      controls) and the liver cholesterol content was 26.2 mg/g compared to 2.3 mg/g in
      the control group. However, 0.15% HOE 402 led to a 48% reduction and 0.20% HOE
      402 to a 80% reduction, in total hepatic cholesterol concentration. There was a
      43% fall in plasma cholesterol level being observed with the higher HOE 402 dose.
      Using the dual isotope plasma ratio method, no inhibition of intestinal
      cholesterol absorption by HOE 402 was found, either in the noncholesterol fed or
      in the cholesterol fed hamsters. Cholesterol feeding diminished the whole LDL
      animal clearance to 393 +/- 17 microliters/h per 100 g animal (control 666 +/- 81
      microliters/h per 100 g). When treated with 0.20% HOE 402, the whole animal LDL
      clearance rate was enhanced 2.3-fold to 824 +/- 66 microliters/h per 100 g. In
      the hamsters fed 0.25% cholesterol alone whole liver LDL receptor activity was
      suppressed to 63 +/- 5%, compared to that in the untreated controls (100%). The
      addition of 0.20% HOE 402 to the cholesterol enriched diet not only reversed this
      suppression, but resulted in a marked stimulation of liver receptor activity to
      165 +/- 15% (whole body LDL receptor activity 141 +/- 10%). These results
      indicate that HOE 402 exerts its lipid lowering effect by a more direct
      activation on hepatic LDL receptor activity rather than by an indirect intestinal
      effect on cholesterol absorption.

PMID- 8555259
TI  - Estrogens protect against hydrogen peroxide and arachidonic acid induced DNA
      damage.
AB  - The ability of estrogens to protect against DNA damage induced by either hydrogen
      peroxide or arachidonic acid alone or in combination with Cu2+ was investigated.
      DNA strand breaks were determined by conversion of double stranded supercoiled OX
      174 RFI DNA to double stranded open circular DNA and linear single stranded DNA.
      Estradiol-17 beta significantly decreased the formation of single and double
      strand breaks in DNA induced by H2O2 alone or with Cu2+. Equilin (an equine
      estrogen) was more effective than estradiol-17 beta at the doses tested.
      Arachidonic acid in the presence of Cu2+ caused the formation of high levels of
      linear DNA which was protected by estrogen with equilen being more effective.
      These studies suggest that estrogens through this protective effect on DNA damage
      might contribute to cardioprotection.

PMID- 8555261
TI  - Tetrahymena thermophila: analysis of phospholipids and phosphonolipids by high
      field 1H-NMR.
AB  - The phospholipids of control and lipid-modified Tetrahymena thermophila were
      identified and quantified, using 1-D and 2-D COSY proton NMR spectroscopy on
      intact lipids, before and after HPLC separation. The results are comparable to
      those obtained using classical lipid analytical techniques. The results indicate
      that the study of enzyme pathways and other metabolic processes involving
      phospholipids in Tetrahymena and related protozoa can be carried out using proton
      NMR spectroscopy as the investigating technique.

PMID- 8555260
TI  - Fatty acid ethyl ester synthesis by human liver microsomes.
AB  - Fatty acid ethyl esters are a family of non-oxidative metabolites of ethanol
      present in many tissues after ethanol consumption. In this report we demonstrate
      the existence in human liver of an acyl-CoA:ethanol acyltransferase activity
      which may be responsible in part for the synthesis of these compounds in vivo.
      The effects of oleoyl-CoA and ethanol concentrations, presence or absence of
      bovine serum albumin and detergent, pH and enzyme concentration on this activity
      have been determined. Acyl-CoA:ethanol acyltransferase activity is localised in
      the membrane-bound fraction. Using inhibitors directed against related enzyme
      activities, it has been shown that the activity is not related to serine
      dependent carboxylesterases or acyl-CoA:cholesterol acyltransferase, but tht it
      may be associated with acyl-CoA hydrolase activity. We have also compared acyl
      CoA:ethanol acyltransferase activity with fatty acid ethyl ester synthase
      activity in microsomes and cytosol from the same liver. Our data indicate that
      these activities are comparable in vitro (on a unit/g liver basis), and suggest
      that both may be significant in vivo.

PMID- 8555262
TI  - Dietary fish oil normalize dyslipidemia and glucose intolerance with unchanged
      insulin levels in rats fed a high sucrose diet.
AB  - The aim of this study was to investigate the relationship between the lipid
      lowering effects of fish oils and concomitant consequences on glucose tolerance
      and insulin sensitivity in an experimental animal model of hypertriglyceridemia
      induced by high sucrose intake. To achieve this goal, male Wistar rats were fed a
      semi-synthetic sucrose rich diet (SRD) (w/w: 62.3% sucrose, 8% corn oil, 17%
      protein) for 90 days. At the time, a well established and permanent
      hypertriglyceridemia accompanied by glucose intolerance was present. After that,
      one half of the animals continued on the SRD up to 120 days. The other half
      received an SRD in which the source of fat was substituted by cod liver oil (w/w
      7% CLO plus 1% corn oil) from day 90 to 120 (SRD+CLO). Control rats were fed a
      semi-synthetic diet (CD) (w/w: 62.5% corn starch, 8% corn oil, 17% protein)
      throughout the 120 days experimental period. Results obtained after the
      experimental period show that the hypertriglyceridemia and glucose intolerance
      ensuing long term feeding normal rats with a sucrose-rich diet could be
      completely reversed mediating no change in circulating insulin levels by shifting
      the source of fat in the diet from corn oil to cod liver oil. These findings
      suggest that manipulation of dietary fats may play a role in the management of
      the lipid disorders associated with glucose intolerance and insulin resistance.

PMID- 8555263
TI  - The characterisation and cyclic production of a highly unsaturated homoserine
      lipid in Chlorella minutissima.
AB  - The marine alga Chlorella minutissima contains DGTS (diacylglyceryl-N,N,N
      trimethylhomoserine) as a major component (up to 44% of total lipids). This lipid
      is absent from other members of the Chlorococcales, except for C. fusca, which
      contains DGTS as 1.3% of total lipids. Contrary to expectation, the DGTS is
      accompanied by PC (phosphatidylcholine) as the major phospholipid. DGTS is
      normally highly saturated in the C-1 position of glycerol, but in C. minutissima,
      both C-1 and C-2 are acylated with EPA (eicosapentaenoic acid, 20:5) in the major
      molecular species (over 90% of total). The DGTS level shows a marked rhythmic
      fluctuation with time which is inversely correlated with the level of MGDG
      (monogalactosyldiacylglycerol), the other major lipid. Improved NMR data and the
      first electrospray MS data on this lipid are presented.

PMID- 8555264
TI  - Effect of short- and long-term treatments by a low level of dietary L-carnitine
      on parameters related to fatty acid oxidation in Wistar rat.
AB  - This study was designed to examine whether short- and long-term treatments by a
      low level of dietary L-carnitine are capable of altering enzyme activities
      related to fatty acid oxidation in normal Wistar rats. Under controlled feeding,
      ten days of treatment changed neither body weights nor liver and gastrocnemius
      weights, but succeeded in reducing the weight of peri-epididymal adipose tissues.
      Triacylglycerol contents were lowered in liver and ketone body concentrations
      were found slightly more elevated in blood. In the liver, mitochondrial carnitine
      palmitoyltransferase I (CPT I) exhibited a slightly higher specific activity and
      a lower sensitivity to malonyl-CoA inhibition, while peroxisomal fatty acid
      oxidizing system (PFAOS) was found to be less active. Carnitine supplied for one
      month reduced the mass of the periepididymal fat tissue, but not those of the
      other studied organs, and produced a slight but non-significant gain in body
      weight after ten days of treatment. In the liver, CPTI characteristics were
      comparable in control and treated groups, while PFAOS activity was less in rats
      receiving carnitine. Data show that L-carnitine at a low level in the diet
      exerted two paradoxical effects before and after ten days of treatment. Results
      are discussed in regard to fatty acid oxidation in mitochondria and peroxisomes,
      and to the possible altered acyl-CoA/acylcarnitine ratio with increased
      concentrations of L-carnitine in the liver.

PMID- 8555265
TI  - Binding of lipoprotein lipase to apolipoprotein B-containing lipoproteins.
AB  - The binding of lipoprotein lipase (LPL) to different lipoproteins and to a lipid
      emulsion was studied. After incubating the same amount of 125I-labelled LPL with
      VLDL, LDL or a lipid emulsion containing no apolipoproteins, we separated the
      free enzyme from the lipoprotein-bound LPL by gel filtration and by lipoprotein
      precipitation with phosphotungstic acid. By the former method we observed that
      all these types of lipid particles bound LPL indicating that the lipid moiety
      accounts for the LPL-lipoprotein interaction. This binding of LPL to lipoproteins
      was disrupted by high salt concentrations. When balanced by the apolipoprotein B
      content, it was observed that a significantly higher amount of 125I-labelled LPL
      co-eluted with VLDL than with LDL in gel permeation. The Kd values for binding of
      LPL to lipoproteins were estimated by use of lipoprotein precipitation. The
      obtained Kd values, both in the absence and in the presence of human lipoprotein
      deficient serum, were lower for VLDL than for LDL indicating a higher affinity of
      LPL for VLDL than for LDL. We finally compared binding capacity of LPL to VLDL
      subfractions with different apo E content. For this, we used apo E-poor (VLDL-B)
      and apo E-rich (VLDL-D) subfractions separated by heparin-Sepharose
      chromatography. We found that 125I-labelled LPL co-eluted to a similar extent
      with both subfractions on gel filtration, and the estimated Kd values from
      lipoprotein precipitation were not statistically different. Taken together, our
      results indicate that the lipid moiety, probably the phospholipids, accounts for
      the LPL-lipoprotein interaction; differences in size, the presence of C
      apolipoproteins or the conformation of apo B may be responsible for the higher
      affinity of LPL for VLDL than for LDL herein observed.

PMID- 8555266
TI  - Morphological observations on the fate of liposomes in the regional lymph nodes
      after footpad injection into rats.
AB  - Multilamellar liposomes composed of equimolar egg phosphatidylcholine and
      cholesterol and containing carboxyfluorescein or colloidal gold were injected
      subcutaneously into the footpad of the hind-leg of rats. The draining popliteal
      lymph nodes of animals killed at time intervals after injection were then
      dissected and sections examined by fluorescence microscopy (carboxyfluorescein),
      light microscopy using an immunogold silver kit to enhance gold particles or by
      transmission electron microscopy. Morphological observations confirmed that
      subcutaneously injected liposomes accumulate in large numbers in the draining
      lymph node. The majority of liposomes arrived at the subcapsular sinuses,
      probably via afferent lymphatic vessels, as such, i.e., in a non-cell bound form.
      Subsequently, liposomes were dispersed throughout the lymph node either by
      permeation as free vesicles along the sinuses or by cells involved in vesicle
      uptake. The majority of such cells were free macrophages, littoral cells and
      reticular cells (fixed macrophages). Once within cells, liposomes were seen
      digested by the lysosomal apparatus with varying loss of their lamellar
      structure, leaving free gold particles within the lysosomes.

PMID- 8555267
TI  - Relative resistance of the hamster to aortic atherosclerosis in spite of
      prolonged vitamin E deficiency and dietary hypercholesterolemia. Putative effect
      of increased HDL?
AB  - Male golden hamsters were rendered hypercholesterolemic by feeding diets enriched
      with cholesterol and fat. In the first series of experiments, 5% butter and 1%
      cholesterol were added to a chow diet and plasma cholesterol levels were
      maintained at 350-390 mg/dl over the entire experimental period. Groups of
      hamsters and their age controls consuming the chow diet, were killed after 7, 15
      and 20 months when the aorta was examined for atherosclerosis by determination of
      cholesterol mass. In the controls, aortic total cholesterol (TC) increased with
      age by 28% and esterified cholesterol increased to 11% of TC. In the
      hypercholesterolemic animals aortic TC was only 28% higher than in the controls
      and cholesteryl ester was also 11.5% of TC. In the second series, one group of
      hamsters were fed a semi-purified diet deficient in vitamin E, containing 1%
      cholesterol and 10% lard; a second group received the same diet, but supplemented
      with vitamin E. Controls consumed local chow. After 7 months on the vitamin E
      deficient diet plasma alpha-tocopherol was 0.05 mg/l, in those supplemented with
      vitamin E it was 20 mg/l, while in the controls it was 3.3 mg/l. Plasma
      thiobarbituric acid reactive substances (TBARS) were higher in the vitamin E
      deficient group and there was a greater propensity of lipoproteins (d < 1.063
      g/ml) to peroxidation in vitro than in the vitamin E supplemented group. Plasma
      cholesterol was 366 mg/dl in the vitamin E deficient, 336 mg/dl in the vitamin E
      supplemented group, and 64 mg/dl in controls. Aortic cholesterol was 79.1 in
      vitamin E supplemented and 84.4 micrograms/10 mg dry weight in vitamin E
      deficient hamsters. In both series of experiments, HDL amounted to 36-41% of
      plasma TC in the hypercholesterolemic animals and 59-62% in the controls. IN
      CONCLUSION: the hamster appears to be quite resistant to atherosclerosis in face
      of sustained hypercholesterolemia, even in the presence of increased peroxidative
      stress caused by vitamin E deficiency. This relative resistance could be related
      to commensurate increase in plasma HDL which was observed in both series of
      experiments. Since vitamin E deficiency did not enhance aortic cholesteryl ester
      deposition, the protective effect of HDL seems to be related to its role in
      reverse cholesterol transport, rather than in prevention of peroxidation.

PMID- 8555268
TI  - Activation of cytosolic phospholipase A2 in permeabilized human neutrophils.
AB  - Neutrophils (PMN) contain two types of phospholipase A2 (PLA2), a 14 kDa
      'secretory' Type II PLA2 (sPLA2) and an 85 kDa 'cytosolic' PLA2 (cPLA2), that
      differ in a number of key characteristics: (1) cPLA2 prefers arachidonate (AA) as
      a substrate but hydrolyzes all phospholipids; sPLA2 is not AA specific but
      prefers ethanolamine containing phosphoacylglycerols. (2) cPLA2 is active at nM
      calcium (Ca2+) concentrations; sPLA2 requires microM Ca2+ levels. (3) cPLA2
      activity is regulated by phosphorylation; sPLA2 lacks phosphorylation sites. (4)
      cPLA2 is insensitive to reduction; sPLA2 is inactivated by agents that reduce
      disulfide bonds. We utilized PMN permeabilized with Staphylococcus aureus alpha
      toxin to determine whether one or both forms of PLA2 were activated in porated
      cells under conditions designed to differentiate between the two enzymes. PMN
      were labeled with [3H]AA to measure release from phosphatidylcholine and
      phosphatidylinositol; gas chromatography-mass spectrometry was utilized to
      determine total AA release (mainly from phosphatidylethanolamine) and to assess
      oleate and linoleate mass. A combination of 500 nM Ca2+, a guanine nucleotide,
      and stimulation with n-formyl-met-leu-phe (FMLP) were necessary to induce maximal
      AA release in permeabilized PMN measured by either method; AA was preferentially
      released. [3H]AA and AA mass release occurred in parallel over time. A
      hydrolyzable form of ATP was necessary for maximum AA release and staurosporin
      inhibited PLA2 activation. Dithiothreitol treatment had little affect on [3H]AA
      release and metabolism but inhibited AA mass release. Assay of cell supernatants
      after cofactor addition did not detect sPLA2 activity and the cytosolic buffer
      utilized did not support activity of recombinant sPLA2. These results strongly
      suggested that cPLA2 was the enzyme activated in the permeabilized cell model and
      this is the first report which unambiguously demonstrates AA release in response
      to activation of a specific type of PLA2 in PMN.

PMID- 8555269
TI  - The desaturation and elongation of linolenic acid and eicosapentaenoic acid by
      hepatocytes and liver microsomes from rainbow trout (Oncorhynchus mykiss) fed
      diets containing fish oil or olive oil.
AB  - The products of desaturation and elongation of [1-14C]18:3(n - 3) and [1
      14C]20:5(n - 3) were studied using hepatocytes and microsomes prepared from
      livers of trout maintained on diets containing either olive oil or fish oil, to
      establish the extent to which the formation of 22:6(n - 3) was enhanced in the
      absence of dietary 22:6(n - 3) and to investigate the pathway(s) of conversion of
      18:3(n - 3) and 20:5(n - 3) to 22:6(n - 3). Levels of 20:5(n - 3) and 22:6(n - 3)
      in the total lipid of hepatocytes from trout fed olive oil were 20-fold and 10
      fold, respectively, lower than in cells from trout fed fish oil. For both dietary
      groups, [1-14C]18:3(n - 3) was incorporated into hepatocyte lipid to a greater
      extent than [1-14C] 20:5(n - 3). Almost 70% of the total radioactivity from [1
      14C]18:3(n - 3) was recovered in hepatocyte triacylglycerols, whereas
      radioactivity from [1-14C]20:5(n - 3) was recovered almost equally in neutral
      lipids (52%) and polar lipids (48%). The products of desaturation and elongation
      from both labelled substrates were esterified mainly into hepatocyte polar
      lipids, whereas elongation products of [1-14C]18:3(n - 3) were preferentially
      incorporated into neutral lipids. Radioactivity recovered in the 22:6(n - 3) of
      polar lipids of hepatocytes from trout fed olive oil, from both 14C substrates,
      was approximately double that in hepatocytes from trout fed fish oil. No
      radioactivity from either [1-14C]18:3(n - 3) or [1-14C]20:5(n - 3) was
      incorporated into 22:6(n - 3) by microsomes isolated from livers from either
      group of fish and incubated in the presence of acetyl-CoA, malonyl-CoA, NADH,
      NADPH, ATP and coenzyme A. However, significant radioactivity was recovered in
      24:5(n - 3) and 24:6(n - 3) from [1-14C]20:5(n - 3) and more radioactive 24:6(n -
      3) accumulated in microsomes from trout fed olive oil than from trout fed fish
      oil. The results establish that the formation of 22:6(n - 3) from both 18:3(n -
      3) and 20:5(n - 3) in hepatocytes of rainbow trout is stimulated by omitting
      22:6(n - 3) from the diet and are consistent with the biosynthesis of 22:6(n - 3)
      in trout liver cells proceeding via 24:5(n - 3) and 24:6(n - 3) intermediates.

PMID- 8555270
TI  - Quaternary nitrogen compounds affect carnitine distribution in rats. Particular
      emphasis on edrophonium.
AB  - Edrophonium (ethyl(m-hydroxyphenyl)dimethylamine) acutely modifies carnitine
      levels in different rat tissues, increasing hepatic and reducing blood and renal
      levels. After 2 h edrophonium treatment, the total serum carnitine levels were
      decreased by 16 (P < 0.001) and 33 (P < 0.001) percent in fed and fasted rats
      respectively compared to control, and in kidney the levels decreased by 11 (P <
      0.05) and 34 (P < 0.001) percent whereas in liver the edrophonium treatment
      increased the levels by 43 (P < 0.001) and 59 (P < 0.001) percent. The
      edrophonium action does not depend on the route of administration or on the
      nutritional state of the animal. Its activity on carnitine levels is neither
      accompanied by significant variation of serum parameters of carbohydrate, fat and
      protein metabolism nor of insulin levels. The edrophonium activity is not related
      to cholinergic action, as physostigmine and ambenonium at concentrations known to
      increase cholinergic activity do not modify carnitine distribution in tissues.
      Trimethylphenylammonium (TPA) and trimethyl(p-aminophenyl)ammonium (TPA.NH2),
      compounds structurally similar to edrophonium, are on the contrary active on
      levels of carnitine and this effect is not related to their cholinergic potency.
      In 24 h fasted rats after the TPA and TPA. NH2 treatment, the total serum
      carnitine levels were decreased by 32 (P < 0.001) and 13 (n.s.) percent
      respectively compared to control, and in kidney the levels decreased by 15 (P <
      0.02) and 5 (n.s.) percent, whereas in liver the treatment increased the levels
      by 72 (P < 0.001) and 45 (P < 0.01) percent. Moreover atropine, an acetylcholine
      antagonist, affects carnitine distribution in a way similar to edrophonium.
      Edrophonium activity on carnitine distribution, probably affects (inter)cellular
      carnitine transport by direct action on plasma membrane. Effect on capillary
      endothelium may be responsible for its observed action on muscle contraction
      force in imminent ischemia.

PMID- 8555271
TI  - Cholesterol-independent membrane disruption caused by triterpenoid saponins.
AB  - The membrane-disrupting activity of 15 triterpenoid saponins, obtained from
      Chinese plants of the genus Aralia, was investigated using phosphatidylcholine
      liposomes with and without cholesterol. The permeability of the membrane was
      examined by monitoring the induced fluorescent dye release from the liposome. On
      the basis of the obtained results, the structure-activity relationship among
      glucuronides of oleanolic acid was discussed. This takes into account
      particularly the variation in the carboxyl function. Namely, the saponins could
      induce a permeability change on liposomal membrane without cholesterol when they
      are glycosylated at both C-3 and C-28 of the oleanolic acid. There also exists a
      great similarity in the time-course curves for dye-release within such saponins,
      reflecting their similar action with the lipid bilayer membrane. The saponins
      glycosylated only at C-3 could also exhibit the same activity with somewhat
      different action profiles when the glucuronic acid is esterified, while those
      with the free glucuronic acid required cholesterol in the liposomes to induce
      permeability change thereof.

PMID- 8555272
TI  - C2-ceramide primes specifically for the superoxide anion production induced by N
      formylmethionylleucyl phenylalanine (fMLP) in human neutrophils.
AB  - Activated sphingomyelinases release ceramide molecules believed to be involved in
      intracellular signalling. The present study investigated whether soluble C2
      ceramide modulates some of the effects of N-formylmethionylleucyl phenylalanine
      (fMLP) and other agonists on human neutrophils (or polymorphonuclear leukocytes
      PMN); principally superoxide anion (O2-) production. The preincubation of PMN for
      15 min with C2-ceramide increased by up to almost 3-fold the amounts of O2-
      generated in response to 0.1 and 1 microM fMLP. Priming was detected at C2
      ceramide concentrations of 2 microM to 4 microM per million PMN. Though less
      potent than C2-ceramide, C6-ceramide (N-hexanoylsphingosine) could prime for O2-
      generated in response to 0.1 microM fMLP, with maximal effects obtained at 10-20
      microM. In contrast, micromolar concentrations of sphingosine, dihydroceramide,
      and ceramide-phosphate, failed to exert any potentiating effect on fMLP-induced
      O2- generation. As expected, TNF-alpha (1000 U/ml), also primed for fMLP-induced
      O2- production; however, the combination of TNF-alpha and C2-ceramide showed no
      additive effect. Moreover, S. aureus sphingomyelinase (0.1 U/ml), was unable to
      reproduce the priming effects of C2-ceramide and TNF-alpha. C2-ceramide at 2
      microM did not enhance the production of O2- induced by 100 nM recombinant human
      interleukin-8 (IL-8), leukotriene B4 (LTB4), platelet-activating factor (PAF) or
      20 mM sodium fluoride (NaF). Furthermore, C2-ceramide (2 microM) did not enhance
      the mobilization of calcium, the release of arachidonic acid or the accumulation
      of phosphatidylethanol, induced by 100 nM fMLP. This suggests that probably
      neither phospholipases C, A2 or D (PLC, PLA2, PLD) were involved in the priming
      effect by C2-ceramide. However, C2-ceramide inhibited in a dose-related manner
      the production of O2- induced by phorbol 12-myristate 13-acetate (PMA) and
      mezerein. Furthermore, PMA-stimulated PLD activity was also significantly reduced
      by a preincubation of PMN with C2-ceramide. The priming of O2- production by C2
      ceramide could involve yet unidentified mechanisms specific for fMLP, or it might
      imply that cytokines such as TNF-alpha have different mechanisms than C2
      ceramide.

PMID- 8555273
TI  - Synthesis of hydroxyeicosatetraenoic (HETEs) and epoxyeicosatrienoic acids (EETs)
      by cultured bovine coronary artery endothelial cells.
AB  - Endothelial cells release several factors which influence vascular tone,
      leukocyte function and platelet aggregation. Some of these factors are
      metabolites of arachidonic acid, most notably prostacyclin. However, many of the
      endothelial metabolites of arachidonic acid have not been positively identified.
      The purpose of these studies is to identify the arachidonic acid metabolites
      synthesized by bovine coronary endothelial cells. Cultured bovine coronary artery
      endothelial cells were incubated with [14C]arachidonic acid. The incubation media
      was extracted and the radioactive metabolites resolved by a combination of
      reverse phase- and normal phase-high pressure liquid chromatography (HPLC). The
      cells synthesized 6-keto prostaglandin (PG)F1 alpha, PGE2, 12
      hydroxyheptadecatrienoic acid (HHT), 12-, 15-, and 11-hydroxyeicosatetraenoic
      acids (HETE), and 14,15-, 11,12-, 8,9-, and 5,6-epoxyeicosatrienoic acids (EET).
      Several of the HETEs were further analyzed by chiral-phase HPLC. The cells
      synthesized predominately 12(S)-, 15(S)-, and 11(R)-HETE. The synthesis of the S
      optical isomers of 12- and 15-HETE suggested that the 12- and 15-lipoxygenases
      were present in these cells. 11(R)-HETE is probably derived from cyclooxygenase.
      They also synthesized smaller amounts of 9-, 8- and 5-HETEs. The structures of
      the HETEs and EETs were confirmed by mass spectrometry. The release of 6-keto
      PGF1 alpha and 15-HETE was measured by specific radioimmunoassays. Melittin,
      thrombin, arachidonic acid and A23187 stimulated the release of both eicosanoids
      in a concentration-related matter. Under all conditions, the release of 6-keto
      PGF1 alpha exceed the release of 15-HETE. Therefore, cultured bovine coronary
      artery endothelial cells synthesize cyclooxygenase, lipoxygenase and cytochrome P
      450 metabolites of arachidonic acid.

PMID- 8555274
TI  - Random drug tests at work: the probability of identifying frequent and infrequent
      users of illicit drugs.
AB  - Random drug testing in the workplace has become more common since federal
      guidelines were issued in 1988, despite the criticism that most positive tests
      are the result of occasional use of illicit drugs. In order to determine the
      relative probabilities of detecting frequent versus infrequent users of illicit
      drugs, a survey of 15 experts in the drug abuse field was conducted. Based on the
      responses, it was estimated that 55% of employed people who used any illicit
      drugs in the prior year were annual drug users, 37% were monthly users, and 8%
      were daily users. Analysis using probability theory indicated that among
      workplace drug users who test positive, 52% will be daily users, 41% will be
      monthly users, and only 7% will be annual users. At a 50% testing rate, random
      drug tests identify 40% of daily users, 8% of monthly users and only 1% of annual
      users during the course of a year. The estimated rate of illicit drug use among
      employees is approximately eight times the average random testing positive rate.
      Random drug tests in the workplace are effective in identifying near daily users
      of illicit drugs, but they are less effective at identifying infrequent drug
      users. Employers have found that random drug testing is a deterrent to both
      frequent and occasional use of illicit drugs.

PMID- 8555275
TI  - Public policy statement on primary medical care for HIV infected patients in
      addiction treatment: American Society of Addiction Medicine.

PMID- 8555276
TI  - Public policy statement on HIV testing of patients in addiction treatment
      facilities: American Society of Addiction Medicine.

PMID- 8555277
TI  - Opiate dependence, comorbidity and seasonality of birth.
AB  - OBJECTIVE: In contrast with the non-opiate dependent population, persons
      biologically-dependent upon opioids display an excess life-time prevalence of
      affective and anxiety disorders. Many of these addicts state that opiates,
      particularly methadone, relieve or diminish the severity of their dysphoria. The
      purpose of this study is to explore this phenomena by analyzing how a specific
      population of long-term addicts (mean years of addiction 16.9, SD 3.8) differs
      from a non-opiate dependent population regarding seasonality of birth. METHODS:
      Birth months were determined for 457 opiate dependent patients, placed onto
      methadone maintenance for intractable opiate dependence, born between 1930-1970
      (sorted by sex, race, year and place of birth), and compared to normal US birth
      statistics. Affective and anxiety disorders were screened for using psychometric
      testing, verified by structured clinical intervals. RESULTS: A significant
      difference was noted when comparing monthly births rates for patients and
      normals. Grouping the monthly data into birth trimesters (Oct-Jan; Feb-May; Jun
      Sep) clearly shows this difference: opioid dependent persons--38.5/29.8/31.8%;
      normals--33.4/32.0/34.7%. As a group, intractable, opioid dependent patients
      demonstrate an increased life-time prevalence, relative to normals, of anxiety
      (27.8 vs. 13.9%), dysthymia (23.4 vs. 6.4%) and combined anxiety + dysthymia
      (17.9 vs. 1.5%); opioid dependent persons born between Oct-Jan demonstrated more
      anxiety (32.0 vs. 25.1%), dysthymia (29.3 vs. 19.5) and combined anx + dys (23.3
      vs. 14.4) than those born in the other two trimesters. CONCLUSION: Persons
      entering methadone maintenance for opiate dependence with comorbid anxiety,
      dysthymia or combined anxiety + dysthymia are more likely to have been born in
      the period of Oct-Jan. This may be due to a higher risk of developmental
      aberrations occurring in infants born during the light-limited portion of the
      year creating a later propensity for intractable, opiate dependence.

PMID- 8555278
TI  - Seroprevalence of hepatitis A, B, C, and D markers and liver function
      abnormalities in intravenous heroin addicts.
AB  - To determine the most prevalent forms of hepatitis in intravenous heroin addicts,
      389 addicts consecutively admitted to outpatient treatment clinics throughout
      California were tested for antibodies to hepatitis A (anti-HAV), B core (anti
      HBc), B surface (anti-HBs), C (anti-HCV), D (anti-HDV), and B surface antigen
      (HBsAg). The majority were also tested for serum alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), alkaline phosphatase, lactic dehydrogenase,
      total bilirubin, globulins, albumin, and platelet count. The seroprevalence of
      each marker was: anti-HAV (40.7%); anti-Hbc (73.6%); anti-HBs (46.7%); anti-HCV
      (93.6%); anti-HDV (9.6%), and HBsAg (3.5%). No single case was positive for IgM,
      anti-HAV, or for both HBsAg and anti-HDV, indicating the presence of recent
      hepatitis A or hepatitis D infection. Abnormal liver enzymes, serum proteins,
      total bilirubin, and platelet count were found to be normal in 5.3 to 44.8% of
      anti-HCV cases indicating persistent infection. Among anti-HCV cases, elevated
      total bilirubin or a low platelet count was invariably associated with one or
      more liver enzyme and protein abnormalities. We conclude that while acute
      hepatitis may be frequent and caused by various viral types, hepatitis C is the
      primary form of chronic hepatitis found in intravenous heroin addicts. Almost
      half of hepatitis C cases demonstrate liver function abnormalities indicating
      persistent infection that has the potential to be contagious and progress to
      cirrhosis, liver failure, and hepatocellular carcinoma.

PMID- 8555279
TI  - Seroprevalence and risk factors associated with HTLV-I/II infection in injection
      drug users in northern New Jersey.
AB  - Data from an AIDS Demonstration Research project in Paterson, NJ, that enrolled
      out-of-treatment injection drug users (IDUs) were analyzed to detect demographic
      patterns and risk factors associated with infection with human immunodeficiency
      virus (HIV) and human T-lymphotropic virus types I or II (HTLV-I/II). Of 410 IDUs
      screened, 44.2% were HIV-positive and 19.3% were HTLV-I/II-positive. African
      Americans were significantly more likely than other racial groups to be HTLV-I/II
      seropositive and to be HIV-seropositive. Over one-fifth of African-Americans--but
      no Latinos or whites--were doubly infected with HIV and HTLV-I/II. In logistic
      regression analysis, African-American race, long-term injection drug use, and age
      were significant predictors of HTLV-I/II-seropositivity. While the associations
      between recent needle practices and HTLV-I/II-seropositivity fell short of
      significance, the trends in the data were consistent with a hypothesis that HTLV
      I/II is transmitted through the sharing of injection equipment. Public health
      implications of the data are discussed.

PMID- 8555280
TI  - Prevalence and improvement in psychopathology in opioid dependent patients
      participating in methadone maintenance.
AB  - Questions continue in the literature concerning potential cause and effect
      relationships between opiate dependency and several organically-based psychiatric
      disorders. For example, does opiate dependency produce secondary anxiety and
      dysthymic syndromes in otherwise healthy persons? or is narcotics misuse by a
      patient an attempt to self-medicate pre-existing psychopathology? Does the
      severity of psychopathologic symptoms decrease with time in treatment? To resolve
      such questions, we routinely conduct psychiatric evaluations on all opioid
      dependent patients enrolled into methadone maintenance. In this study, we report
      upon treatment outcomes for a cohort of 71 patients evaluated for psychopathology
      upon intake and followed up after being in treatment for a mean time of 24.5 (SD
      8.0) months. Based upon objective psychometric testing with confirmatory clinical
      interview, significant, longitudinal improvements were seen in the symptom
      severity of anxiety and dysthymia present upon intake evaluation. Personality
      profiles also improved with treatment. In general, patients presenting with more
      severe psychopathology required more visits with professional staff in order to
      stabilize their life situations and personal relationships. No correlation was
      noted between drug use and severity of psychopathology. Data support the thesis
      that many opioid dependent patients are self-medicating themselves for
      preexisting organic psychopathology, most commonly, a combined anxiety-dysthymia
      syndrome. Improvement seems to occur secondary to the mood stabilizing properties
      of methadone in disorders thought to be mediated or moderated by endogenous
      endorphins rather than because of psychotherapeutic interventions.

PMID- 8555281
TI  - Availability of reliable serum methadone determination for management of
      symptomatic patients.
AB  - Methadone, when used in the appropriate dose, prevents opioid withdrawal during
      the 24-hour period following medication. However, the appropriate dose for a
      given patient may be difficult to determine due to variations in methadone
      metabolism which is affected by many factors. Early opioid withdrawal, requiring
      a higher dose of methadone, is often difficult to diagnose because many of the
      symptoms are also symptoms of other syndromes common in the methadone maintenance
      population. In this study, ten patients in stable methadone maintenance treatment
      reporting > or = 4 Himmelsbach signs of abstinence were compared with ten
      patients reporting fewer symptoms. Until recently, accurate, precise, and
      affordable determination of serum methadone level has not been readily available
      from commercial laboratories. This study has found that such measures are now
      available. Serum specimens from each subject were sent to three commercial
      laboratories for determination of serum methadone level. Results from the three
      laboratories were highly correlated. No statistical correlation was found between
      serum methadone level and number of Himmelsbach signs. Of the subjects reporting
      four or more symptoms, 40% had low serum methadone levels ( < 150 ng/ml); 60% did
      not. Of the subjects reporting fewer than four symptoms, 90% had serum methadone
      levels > or = 150 ng/ml. Subjects with > or = 4 Himmelsbach signs had lower dose
      adjusted serum methadone levels, the amount of methadone circulating per mg dose,
      (t = 1.54, p < .0702). Thus, for patients who report symptoms which could be
      attributable to opioid withdrawal, measurement of serum methadone level may help
      to differentiate complaints due to early abstinence from those due to other
      medical conditions.

PMID- 8555282
TI  - Buprenorphine as a pharmacotherapy for cocaine abuse: a review of the evidence.
AB  - The partial mu-opiate agonist, buprenorphine, is the subject of recent evaluation
      as a potential pharmacotherapy for cocaine dependence. This paper reviews the
      extant preclinical and clinical evidence of buprenorphine effectiveness in
      treating cocaine abuse, including data from our large methadone comparison trial
      and a smaller buprenorphine dose ranging study. Although buprenorphine appears to
      reduce cocaine self-administration in studies of non-opiate dependent animals,
      clinical evidence for the same response in opiate addicts abusing cocaine has not
      been demonstrated. Further efficacy trials should await preclinical
      demonstrations of effectiveness in samples with opiate and cocaine exposure.

PMID- 8555283
TI  - [Qualitative and quantitative assessment of exposure to geomagnetic field
      variations on the functional status of the human brain].
AB  - The comparison of functional dynamics of human brain with reference to
      qualitative and quantitative characteristics of local geomagnetic field (GMF)
      variations was conducted. It was showed that just local GMF variations can be a
      principal reason of modulation the human brain's functional state. The steady and
      unsteady states of human brain can be determined: by geomagnetic disturbances
      before the observation period; by structure and doses of GMF variations; by
      different combinations of qualitative and quantitative characteristics of GMF
      variations. The optimal level of GMF activity, manifested in periodic
      oscillations in certain amplitude-frequency range is demanded for steady brain's
      functional state. The decrease of optimal GMF activity level and the appearance
      of aperiodic disturbances of GMF can be a reason of unsteady brain's state.

PMID- 8555284
TI  - [Effect of environmental cyclicity on appearance of human brain functional
      asymmetry].
AB  - The indices of the brain functional asymmetry of 4373 persons, born in 1920-1984
      were studied in connection with parameters of the environment during the periods
      of birth and conception. The trustworthy valuable seasonal and long-term
      variations of the brain functional asymmetry indices were discovered. Their
      correlation with the cosmo-physical fluctuations is maximum for the 10-year cycle
      of the oriental calendar elements and the month of conception. The leading
      factors of the environment are: the parameters of the interplanetary magnetic
      field; the long-period part's potential of the high-tide forming strength of the
      Moon and the Sun G; geomagnetic perturbation Kp; the joined location of the
      planets in relation of the Moon, the Earth and the Sun. The results trace the
      distinctly marked sexual dimorphism. The variability of the brain functional
      asymmetry appears to be the display of the human individuality diversity in time
      and is attended by the changes in the dominating type of the universe cognition
      in the society-logical, intuitive, sensual, combined. The long-term and century
      old cycles of social development seem to be the consequence of this phenomenon.

PMID- 8555285
TI  - [Is there a correlation between cosmophysical factors and emergence of manic
      depressive psychosis?].
AB  - Do the changes of the phases of bipolar, manic-depressive, behavior correlate
      with cosmic periodic processes? In a preliminary study, it was found that cosmic
      patterns such as planetary locations in relation to the lunar month could be
      correlated with the susceptibility to bipolar manic-depressive syndrome, in some
      cases. This paper describes the algorithms used to determine this correlation.
      The result suggest that it could be possible to anticipate cyclic patterns in
      some types of manic depressive disorders so that treatment could be more
      sensitive to the needs of the individual patient.

PMID- 8555286
TI  - [Possible mechanism of operator influence on magnetic-measuring systems].
AB  - Influence of operator on magnetic measuring systems is investigated. Mechanism of
      the influence based on conductivity increasing between the electric scheme
      elements under operator influence is proposed.

PMID- 8555287
TI  - [The effect of heliogeophysical parameters on the ecological situation].
AB  - In the present work the possible connections of the variations of
      heliogeophysical parameters with the some biospherical processes are
      investigated. The correlation of road-transport accidents, development of some
      human illnesses and the character of behaviour of epizootic plague centers with
      variations of this heliogeophysical parameters are considered. The usage of the
      study of variations of the spectral power of cosmic rays for prediction of state
      of near cosmic space is discussed.

PMID- 8555288
TI  - [Statistical properties of the variability of medical indicators during
      heliogeophysical disturbances].
AB  - Possibility of using the impulse noise model for description the medical indexes
      variations during heliogeophysic disturbances is discussed. Possibility of
      probability forecasting the human health damage on base of the Poisson model is
      showed. Comparison was made between model calculations and experimental data and
      reasonable agreement was obtained.

PMID- 8555289
TI  - [Experience in using a diagnostic magnetometer in emergency care].
AB  - A new class of diagnostic magnetometric devices--magnetic storm indicators was
      created at the IZMIRAN. Magnetic storm indicators have the following advantages:
      small weight and dimensions, efficiency, low power consumption and low prices.
      Magnetic storm indicators could be used in medicine, in geophysics and for
      special purposes. Magnetic storm indicators could be used to determine and
      indicate the magnetic storm amplitudes in any region of the Earth in real time
      scale. In the paper we summarized the results of experimental works in clinics
      and shown a principle possibility of magnetometric equipment application for
      magnetic storm registration under conditions of industrial noises in urban
      environment.

PMID- 8555290
TI  - [Dynamics of social processes and geomagnetic activity. 1. Periodic components of
      variations in the number of recorded crimes in Moscow].
AB  - The dynamics of crime activity in Moscow for 14 years of continuous daily
      registration is characterized by exponent growth of registered crime number. On
      background of this trend are observed harmonic components, periods of which in
      the majority correspond to periods of variations of geomagnetic field
      disturbances. The data on crime activity correlate with fluctuations of Ap-index
      of geomagnetic variations.

PMID- 8555291
TI  - [Some heliogeophysical characteristics of a series of especially dangerous
      crimes].
AB  - Geo- and heliophysical situations have been evaluated specially for the days of
      serial crimes committed during 1980-1990 in USSR. The analysis of 150 episodes
      (ten separate series) shows that the crimes are most probable immediately or 1-3
      days after sharp decrease of solar activity (Wolf numbers), geomagnetic activity
      (A3 and K indices) and of lowest daily surface and air temperature.

PMID- 8555292
TI  - [Fluctuations in biophysical measurements as a result of variations in solar
      activity].
AB  - A theory is proposed to explain variations in the net electrical charge of
      biological substances at the Earth's surface. These are shown to occur in
      association with changes in the solar wind and geomagnetic field. It is suggested
      that a liquid dielectric's net volume charge will imitate pH effects, influence
      chemical reaction rates, and alter ion transfer mechanisms in biophysical
      systems. An experiment is described which measures dielectric volume charge, or
      non-neutrality, to allow correlation of this property with daily, 28-day, and 11
      year fluctuation patterns in geophysical and satellite data associated with solar
      activity and the interplanetary magnetic field.

PMID- 8555293
TI  - [Infradian rhythm of functional status of neutrophils and lymphocytes from blood
      of rats with various constitutional features].
AB  - The rhythmical oscillations of the functional condition indicators in neutrophils
      (the peroxidase, the lipids) and in lymphocytes (the succinic and
      glycerophosphate dehydrogenases) with the periods: 17 +/- 1.2; 13.6 +/- 1.6; 9.7
      +/- 1.0; 7.2 +/- 0.5; 3.5 +/- 0.2 days have been revealed in the rats with the
      low, middle and high motive activity in the "open field" test. It has been
      elucidated, that the amplitudes of the revealed rhythms, the phasal correlations
      as well as the degree of the indicators synchronization between each others
      differ in the animals with the different constitutional peculiarities.

PMID- 8555294
TI  - [Biological effects of planetary magnetic storms].
AB  - Six physiological parameters of cardio-vascular system of rabbits and
      ultrastructure of cardiomyocytes were investigated during two planetary
      geomagnetic storms. At the initial and main phase of the storm the normal
      circadian structure in each cardiovascular parameter was lost. The asynchronicity
      was growing together with the storm and abrupt drop of cardia activity was
      observed during the main phase of storm. The main phase of storm followed by the
      destruction and degradation of cardiomyocytes. Parameters of cardia activity
      became substantially synchronized and characterised by circadian rhythm structure
      while the amplitude of deviations was still significant at the recovery stage of
      geomagnetic storm.

PMID- 8555295
TI  - [Modification of reactions of rats to the effect of weak variable magnetic fields
      using a stress factor].
AB  - Stress-factor (hypokinesia) modifies the reaction of the adaptation, which
      develops under the changeable magnetic fields influence with 8 Hz frequency and 5
      microT induction. It's being corroborated by the decrease of nonspecific
      resistance in the initial adaptation period, by the increase of central nervous
      system excitability, by the absence of catecholamines accumulation in the
      hypothalamus and in adrenal glands.

PMID- 8555296
TI  - [Activity of neurons in the parietal associative cortex in the area of the
      substantia nigra in cats exposed to magnetic fields with an 8 Hz frequency].
AB  - The effects of magnetic field (frequency--8 Hz, induction--20 microI, exposition
      time--6 min) on movement--related activity of neocortex neurons and spontaneously
      firing nigral unit's of awake cats were studied. Exposure to field produced the
      modulation of the early neuronal activity preceding self-initiated arm movements
      in parietal cortex (area 5) and the increase of nigral cells firing rate.

PMID- 8555297
TI  - [Effect of interplanetary and geomagnetic disturbances on the increase in number
      of clinically serious medical pathologies (myocardial infarct and stroke)].
AB  - We determined with high accuracy the effect in intense geomagnetic storms on
      myocardial infarction an brain-stroke pathologies. We analysed the large set of
      data collected in Moscow from 1979 to 1981, we cleaned up the data by the first
      harmonic of the annual variation, and by the first three harmonics of the 7-day
      variations (7.0; 3.5; 2.3 days). We found that geomagnetic storms, producing
      large decreases in the cosmic ray intensity, increase the infarction rate by a
      factor 1.13 with a statistical confidence of 9 sigma and the brain stroke rate by
      a factor 1.07 with a statistical confidence of 4.5 sigma.

PMID- 8555298
TI  - [The role of biological clocks in formation of standards, pathology, and in
      therapy. 1. Chronobiological aspects of formation of blood pressure in children
      with positive and negative family history of relatively high blood pressure].
AB  - There are a difference in average values and in amplitudes of about-7 and monthly
      rhythms of infants' blood pressure with positive and negative family history to
      the hypertension. Chronobiological approach to these problem can reveal
      hypertension risk at the early stage of life.

PMID- 8555299
TI  - [Role of biological clocks in normal conditions, pathology, and in therapy. 2.
      Clinical chronoradiotherapy of lung cancer].
AB  - The present study tests whether body core temperature can serve as a marker
      rhythm for guiding the timing of the radiotherapy of lung cancer. It was shown
      that the treatment by radiation at the time of peak core temperature has more
      effectively then treatment at other circadian stages here investigated.

PMID- 8555300
TI  - [Enzymatic status of blood leukocytes, cerebral hemodynamics and the
      environment].
AB  - The present work is concerned with the problem of the enzymic status of blood
      leucocytes in the pathology of non-pregnant women and cerebrohaemodynamics in
      children. The interrelation between the enzymic status of blood leucocytes of non
      pregnant women and cerebrohaemodynamics parameters of infants and natural
      environmental factors are discussed.

PMID- 8555301
TI  - [Pneumocystis carinii infection in AIDS patients. Current prognosis of the
      respiratory insufficiency].

PMID- 8555302
TI  - [Investigation of an outbreak of water-borne typhoid fever in Catalonia in 1994].
AB  - BACKGROUND: Typhoid fever incidence in Spain, and particularly in Catalonia has
      decreased significantly since 1985. Water borne outbreaks can affect large
      numbers of people. These two reasons make specially interesting to study all
      suspected typhoid fever outbreaks, like the one that happened in March 1994 in
      Bages county (Barcelona). METHODS: Epidemiological questionnaires were conducted
      to investigate the origin of the outbreak, the presence of related cases in the
      same area, and the household contacts of cases S. typhi isolates were
      characterized by serotyping, biotyping, phage-typing, ribotyping and pulsed field
      gel electrophoresis analysis of DNA. RESULTS: Nine cases were identified. All
      cases were treated with antibiotics, with clinical success. There were not
      secondary cases. The possible origin was a drinking fountain. All the strains had
      the same epidemiological marker patterns. CONCLUSIONS: Breaking of the sewer
      pipes near to the drinking fountain was probably the origin of the contamination.
      It can be concluded the importance of keeping a good epidemiological control
      system to investigate and prevent outbreaks. It is also important to control the
      drinking fountains to prevent its contamination. Finally it is necessary to
      highlight the utility of epidemiological markers to fully characterized the
      involved strains.

PMID- 8555303
TI  - [Enterococci isolated from blood (1989-1993): evolution of antibiotic
      susceptibility].
AB  - BACKGROUND: The incidence of enterococci infection is on the rise. Treatment is
      ever more difficult due to the intrinsic resistance to many antimicrobial and
      their ability to acquire new resistance. The aim of this study was to: a)
      determine the antibiotic sensitivity of 80 enterococci strains isolated from
      blood in 1989-1993 and, b) detect the possible changes in the resistance patterns
      over this period. METHODS: Eighty enterococci strains isolated from blood
      cultures, since 1989 to 1993 were studied. Sixty-nine were Enterococcus faecalis
      and 11 Enterococcus faecium. The minimum inhibitory concentrations (MIC) of 11
      antimicrobial was determined by the agar dilution method. The Mantel-Haenszel and
      Fisher tests were used for statistical analysis of the results. RESULTS: All the
      strains were sensitive to ampicillin and vancomycin. A high level of resistance
      (HLR) to gentamycin and streptomycin was observed in 18.7% and 23.7%,
      respectively of the strains. Fourteen strains (17.7%) presented HLR to both
      antibiotics. Approximately one third of the strains were resistant to the
      fluoroquinolones tested. Analysis of the results by year only demonstrated a
      significant lineal trend of resistance for ofloxacin (p = 0.014) and a
      significant difference between the years for ciprofloxacin (p = 0.017). Strains
      with an MIC > or = 16 mg/l of fluoroquinolones presented HLR to gentamycin (p <
      0.001) and to all the aminoglucosides (p < 0.001). CONCLUSIONS: The incidence of
      antibiotic resistance of enterococci isolated from blood in the authors hospital
      is generally low and, with the exception of the fluoroquinolones, did not
      demonstrate any significant differences during the period studied. Periodic
      updating and analysis of sensitivity results are required to monitor any changes
      which may occur over time.

PMID- 8555304
TI  - [Comparison of 3 culture methods for genital mycoplasmas].
AB  - BACKGROUND: To compare and evaluate two commercial methods for Mycoplasma hominis
      and Ureaplasma urealyticum with the isolation in agar A7 medium. METHOD: One
      hundred and twenty three vaginal and cervical swabs in women prostitutes, and
      urethral swabs in men, were studied for Mycoplasma hominis and Ureaplasma
      urealyticum isolation in agar A7 medium (BioMerieux; France), Mycoplasma IST
      (BioMerieux, France) and MycoFast ALL-IN (Unipath, U.K.). RESULTS: Of all 123
      samples studied, it was isolated 24 Mycoplasma hominis (19.5%) and 56 Ureaplasma
      urealyticum (45.5%) in agar A7. The sensitivity was 100% for Mycoplasma hominis
      and Ureaplasma urealyticum in Mycoplasma IST versus 29.2% and 50% in MycoFast ALL
      IN, both respectively. Specificity was lower for Ureaplasma urealyticum (59.7%)
      in Mycoplasma IST than in MycoFast ALL-IN (100%). It was found a tetracycline
      resistance of 15% and 12.5% for Ureaplasma urealyticum and Mycoplasma hominis,
      both respectively. CONCLUSIONS: The use of commercial methods permits to count
      the genital mycoplasmas, being Mycoplasma IST better than MycoFast ALL-IN for
      Mycoplasma hominis isolation. Both methods have limitations for Ureaplasma
      urealyticum and they require the use of agar A7. Mycoplasma IST could be a good
      method to survey tetracycline resistance.

PMID- 8555305
TI  - [Prevalence of intestinal parasites in a student population].
AB  - OBJECTIVE: We performed a transversal descriptive study to know the prevalence of
      intestinal parasites of our children's community. A 891 fecal sample analyzed
      from an equal number of apparently healthy children, whose ages were between 5-14
      years old, randomly selected by stratified sampling by years old. RESULTS: The
      study included 297 children of which 133 were parasitized. The percentage of
      parasitization obtained was of 44.78%; no differences with regard to sex. The
      16.53% was poly-parasitic. The mean age of the parasitized subjects was 9.3 years
      old. The species encountered by decreasing frequency were: Giardia lamblia
      (36.36%), Entamoeba coli (10.43%), Entamoeba hartmanni (2.02%), Endolimax nana
      (1.34%), Enterobius vermicularis (1.34%), Ascaris lumbricoides (0.67%) and
      Trichuris trichiura (0.67%). CONCLUSIONS: The frequency of intestinal parasites
      is high in school-age children, probably due to the mid-low to low socioeconomic
      level to which this age-group belongs. The most-found parasite was Giardia
      lamblia. Significant differences (p <0.001) were only seen between the mean ages
      of parasitized subjects of Giardia and Entamoeba coli.

PMID- 8555306
TI  - [Soft-tissue infection caused by Aeromonas hydrophila].
AB  - BACKGROUND: Two cases of soft tissue infection by Aeromonas hydrophila are
      presented with review of the literature. PATIENTS AND METHODS: Two cases of soft
      tissue infection by Aeromonas hydrophila diagnosed from 1992-1993 are reported.
      RESULTS: Most soft tissue infection produced by Aeromonas organisms are caused by
      Aeromonas hydrophila. These infections predominantly affect the lower limbs of
      middle-aged males with previous history of injury favoring infection. The most
      common clinical presentation is cellulitis with a good prognosis if bacteremia is
      not produced. Antibiotics, such as mainly third generation cephalosporins,
      imipenem, aztreonam, cotrimoxazole, tetracycline, chloramphenicol, quinolones and
      aminoglucosides (except streptomycin) are usually very active in vitro against
      these organisms. Surgery is often necessary to cure the process. CONCLUSIONS:
      Cellulitis by Aeromonas hydrophila is a very infrequent entity in Spain and is
      usually associated to previous injury and probable contamination by environmental
      bacteria.

PMID- 8555307
TI  - [Spondylodiscitis caused by Enterococcus: an unusual entity].
AB  - BACKGROUND: Spondylodiscitis by enterococcus is a very infrequent disease with
      only 2 cases caused exclusively by this microorganism having been reported in the
      literature. METHODS: Two clinical cases of spondylodiscitis by enterococcus
      diagnosed in the authors' department are presented with the clinical, radiologic
      and evolutive features of both. RESULTS: In the first case the spondylodiscitis
      was secondary to endocarditis with lumbosacral involvement and formation of an
      anterior epidural inflammatory mass. The second case was the consequence of an
      infection of urinary origin with lumbosacral involvement. Both patients responded
      favorably with only antibiotic treatment. CONCLUSIONS: Spondylodiscitis by
      enterococci is an unusual disease with no therapeutic experience. The authors
      report 2 cases which were treated exclusively with antibiotics.

PMID- 8555308
TI  - [Current clinical problems in evaluating microbiological and pharmacological
      data].

PMID- 8555309
TI  - [Erythematovesicular plaque on the malar region].

PMID- 8555310
TI  - [Septic shock and skin lesions].

PMID- 8555311
TI  - [Didanosine].

PMID- 8555312
TI  - [Eikenella corrodens infections].

PMID- 8555313
TI  - [Multiple liver abscesses of amebic origin].

PMID- 8555314
TI  - [Attempted suicide using massive doses of zidovudine].

PMID- 8555315
TI  - [Epidemiology of a hospital outbreak of scabies].

PMID- 8555316
TI  - [Subacute infectious endocarditis caused by Cardiobacterium hominis. Presentation
      of a case].

PMID- 8555317
TI  - [Experience with a direct immunofluorescence method for detecting Giardia lamblia
      cysts in feces].

PMID- 8555318
TI  - [Ulcer in the urethral meatus and HIV infection].

PMID- 8555319
TI  - [Bacteroides fragilis endocarditis].

PMID- 8555320
TI  - Interspecific variations in adhesive protein sequences of Mytilus edulis, M.
      galloprovincialis, and M. trossulus.
AB  - Variation in the adhesive protein gene sequences of Mytilus edulis, M.
      galloprovincialis, and M. trossulus collected in Delaware, Kamaishi (Japan), and
      Alaska, respectively, was analyzed by the polymerase chain reaction (PCR) using
      two sets of oligonucleotide primers. The first set, Me 13 and Me 14, was designed
      to amplify the repetitive region. The length of the amplified fragments was
      highly variable, even among samples of the same species. Another set, Me 15 and
      Me 16, was designed to amplify a part of the nonrepetitive region. The length of
      the amplified fragments was uniform in each species and differed
      interspecifically; 180, 168, and 126 bp for M. edulis, M. trossulus, and M.
      galloprovincialis, respectively. The amplified sequence of M. trossulus resembled
      that of M. edulis. Mussels from other sites were also examined by PCR using Me 15
      and Me 16. Wild mussels from Tromso (Norway) and cultured mussels from Brittany
      (France) were identified as M. edulis. Cultured mussels from the Mediterranean
      coast of France and wild mussels from Shimizu (Japan) were identified as M.
      galloprovincialis. Some wild mussels from Hiura (Japan) were identified as a
      hybrid between M. galloprovincialis and M. trossulus. Thus, the length of this
      part (variable region) of the sequence is proposed as a diagnostic marker for
      these three morphologically similar species and their hybrids.

PMID- 8555321
TI  - Are solutions presently used bioincompatible?

PMID- 8555322
TI  - The biology of the mesothelium during peritoneal dialysis.
AB  - Substantial derangements of mesothelial biology are observed during experimental
      simulations of dialysis conditions, inferred from the content of human dialysis
      effluent and visualized by microscopy of human mesothelial biopsies. Can
      osmotically active solutions be made biocompatible with the osmoregulatory system
      of the mesothelium? Can the contributions of the mesothelium to host defenses
      against inflammation and/or infection be supported during CAPD? Do underlying
      metabolic derangements present in various kidney diseases and end-stage renal
      disease, regardless of cause, require customized CAPD protocols and solutions?
      Use of dialysis solutions less directly toxic to the mesothelium is a necessary
      step toward some day manipulating peritoneal biology by pharmacological and
      therapeutic modalities.

PMID- 8555323
TI  - First-line defense mechanisms in the peritoneal cavity during peritoneal
      dialysis.

PMID- 8555324
TI  - The cytokine network controlling peritoneal inflammation.

PMID- 8555325
TI  - In vitro studies on the effect of dialysis solutions on peritoneal leukocytes.
AB  - Within the limitations of the various experimental protocols there appears to be
      agreement in the literature that unused dialysis fluids, at least when studied in
      vitro, adversely affect multiple leukocyte functions. The effects of dialysis
      fluids on leukocytes that have been reported to date include: 1. Decreased cell
      viability of PMNs, PM phis, PBMCs, and lymphocytes; 2. Inhibited phagocytosis and
      bacterial killing of various microorganisms by PM phis, PMNs, and peripheral
      blood leukocytes; 3. Reduced secretion of leukotrienes (LTB4, LTC4) from
      peritoneal and peripheral blood PMNs and PBMCs; 4. Reduced secretion of
      prostaglandins (PGE2, TXB2 and 6-keto-PGF1 alpha) from PM phi; 5. Decreased
      production of many cytokines including TNF alpha, IL-8, and IL-6 in PM phis and
      PBMCs. In addition, several studies targeting the potential mechanisms by which
      dialysis solutions inhibit leukocyte function identified the initial low pH of
      the fluids in combination with their lactate content as being of primary
      relevance, since they may lead to a rapid intracellular acidification of
      leukocytes. Moreover, some studies indicated the importance of fluid
      hyperosmolarity and excessive glucose concentrations. These results are
      indirectly supported by recent in vitro investigations of alternative fluids,
      which showed improved leukocyte function following exposure to solutions with
      neutral pH, bicarbonate buffer instead of lactate, or normal osmolarity due to
      use of an alternative osmotic agent (e.g., glucose polymer). In conclusion, the
      evidence obtained during in vitro experimentation suggests that current dialysis
      fluids are, indeed, not biocompatible. However, whether this also bears
      physiological relevance in vivo remains to be established in controlled clinical
      trials comparing conventional fluids to alternative solutions with improved
      biocompatibility. With regard to the future development of in vitro models for
      biocompatibility assessment, the following guidelines are suggested: 1. Cell
      functional parameters should be studied in more than one cell population; 2.
      Depending on which fluid aspect is under investigation, short or even very short
      exposure times should be used (e.g., < 30 min for pH/buffer studies; < 4 hours
      for osmolality/osmotic agent studies); 3. In case the parameter/readout of
      interest requires longer study periods than indicated above (e.g., studies of
      cytokine induction or surface receptor expression), preincubation/recovery models
      should be preferred over coincubation experiments.

PMID- 8555326
TI  - Lactate-versus bicarbonate-based peritoneal dialysis solutions.

PMID- 8555327
TI  - Biocompatibility in peritoneal dialysis: definitions and mechanisms.

PMID- 8555328
TI  - Heat sterilization of glucose-containing fluids for peritoneal dialysis:
      biological consequences of chemical alterations.

PMID- 8555329
TI  - Peritoneal dialysis solution biocompatibility testing in animals.

PMID- 8555330
TI  - Biocompatibility of various osmotic solutes.

PMID- 8555331
TI  - Physiological approaches to increase biocompatibility of peritoneal dialysis.

PMID- 8555332
TI  - Durability of the peritoneal membrane.

PMID- 8555333
TI  - Morphology of the peritoneum: effect of peritoneal dialysis.

PMID- 8555334
TI  - The role of TGF-beta in growth inhibition of peritoneal mesothelial cells in high
      glucose dialysate.

PMID- 8555335
TI  - Industry perspectives on biocompatibility of peritoneal dialysis solutions.

PMID- 8555336
TI  - The role of endothelial cells in the systemic inflammatory response syndrome and
      multiple system organ failure.

PMID- 8555337
TI  - Intraosseous infusion of a small volume of hyperosmotic fluid increases mean
      arterial pressure and lessens the catecholamine response in pigs with
      haemorrhagic shock.
AB  - OBJECTIVE: To measure the plasma catecholamine concentrations during an episode
      of haemorrhagic shock treated by intraosseous infusion of a small volume of
      hyperosmotic fluid in a standardised porcine model. DESIGN: Randomised open
      study. SETTING: University hospital, Norway. MATERIAL: 14 piglets. INTERVENTION:
      Two groups of piglets (n=7 each) were anaesthetised with ketamine and bled to a
      mean arterial pressure of 40 mm Hg. After 30 minutes the animals were randomised
      to receive 100 ml of either hyperosmotic (2.4 mo/l) or iso-osmotic (0.29 mo/l)
      fluid (equal volumes of glucose and sodium chloride) into the tibial bone marrow.
      MAIN OUTCOME MEASURES: Short term (70 minutes) observation of changes in
      haemodynamic, biochemical and hormonal variables. RESULTS: The hyperosmotic
      infusion significantly improved the circulation (mean arterial pressure and
      cardiac index) compared with the iso-osmotic infusion (p < 0.05). The increased
      plasma catecholamine concentrations returned to the reference ranges 20 minutes
      after the hyperosmotic infusion, and were significantly different (p < 0.05) from
      the catecholamine concentrations observed in the iso-osmotic treatment group.
      CONCLUSION: Intraosseous hyperosmotic resuscitation increases the circulatory
      performance and reduces the plasma catecholamine concentrations during
      haemorrhagic shock in pigs.

PMID- 8555338
TI  - Infective complications after minor operations in patients infected with HIV:
      role of CD4 lymphocytes in prognosis.
AB  - OBJECTIVE: To find out the incidence of wound infection in patients with HIV and
      reduced counts of CD4 lymphocytes. DESIGN: Open study. SETTING: University
      hospital, Spain. SUBJECTS: 70 patients with HIV infection and enlarged lymph
      nodes. INTERVENTIONS: Biopsy of lymph nodes and withdrawal of a sample of blood
      for counts of CD4 lymphocytes and neutrophils. MAIN OUTCOME MEASURE: Development
      of infection at the biopsy site, and correlation of infecting organism with
      culture taken at the time of biopsy. RESULTS: Patients were divided into three
      groups depending on their CD4 count: more than 500 cells/ml (n = 26), 200-500
      cells/ml (n = 24), and less than 200 cells/ml (n = 20). Their neutrophil counts
      were 5.1, 3.8, and 2.5 x 10(9)/1, respectively. There were found four wound
      infections (6%); 2 were in the group with more than 500 CD4 cells/ml, and these
      were caused by Staphylococcus aureus (which had been grown from nodes in 6
      patients at the time of biopsy). The other 2 were in the group with less than 500
      cells/ml and these were caused by Mycobacterium tuberculosis; cultures of the
      nodes had shown Staphylococcus epidermidis (n = 3) and M tuberculosis (n = 17).
      There were no infections in the group with 200-500 CD4 cells/ml, in which S
      epidermidis (n = 5) and M tuberculosis (n = 8) had been cultured from the lymph
      nodes. CONCLUSIONS: The CD4 count was of no prognostic importance in the
      development of wound infection, but severe depression of the CD4 count may
      increase the risk of atypical wound infections.

PMID- 8555339
TI  - High long term recurrence rate after subtotal thyroidectomy for nodular goitre.
AB  - OBJECTIVE: To establish the long term recurrence rate in patients operated on for
      nodular goitre and to find out if oral treatment with thyroxine reduces this
      risk. DESIGN: Retrospective study. SETTING: District hospital, Sweden. SUBJECTS:
      43 patients who underwent subtotal thyroidectomy for nodular goitre (36 non
      toxic, 7 toxic) from 1960-65, and who were re-examined in 1993; 11 patients were
      given oral thyroxine during the postoperative period and the remaining 32 had no
      medical treatment. MAIN OUTCOME MEASURES: Recurrence of goitre. RESULTS: 5/11
      goitres recurred in the thyroxine group (45%) and 13/32 (41%) in the untreated
      group. CONCLUSION: The recurrence rate of nodular goitre is high 30 years after
      subtotal thyroidectomy. Long term oral thyroxine does not seem to change the
      picture.

PMID- 8555340
TI  - Surgical mortality and morbidity in malignant obstructive jaundice: a prospective
      multivariate analysis.
AB  - OBJECTIVE: To construct prognostic scores using multivariate analysis for
      morbidity and mortality in jaundiced patients with malignant biliary obstruction.
      DESIGN: Prospective study. SETTING: 16 university and 12 general hospitals
      affiliated to the French Association for Surgical Research. MAIN OUTCOME
      MEASURES: Results of application of severity indexes for mortality and morbidity
      constructed from 17 variables. That for mortality was: 0.0497 x age + 0.9219 x
      American Society of Anesthesiologists' (ASA) grade + 0.0037 x serum bilirubin
      concentration minus 0.0239 x prothrombin time + 0.0001 x white cell count minus
      5.593. That for morbidity was: minus 0.7499 x ASA grade + 0.0294 x prothrombin
      time + 1.4220 x cause (0 = carcinoma of bile duct, 1 = pancreatic cancer) minus
      1.5080 x operation (0 = bypass, 1 = resection) minus 1.537. RESULTS: The scores
      correctly predicted mortality in 77% and morbidity in 65% (infective morbidity in
      73%). CONCLUSIONS: We recommend that when the mortality index is negative
      operation should be the treatment of choice, and when it is positive the patient
      should be advised to have non-surgical palliative treatment. When the morbidity
      index is negative the risk of complications is high, and when it is positive the
      risk is low. The application of these indexes allows for better choice of
      patients suitable for operative treatment of malignant biliary obstruction.

PMID- 8555341
TI  - Laser welding of everted enterotomies in rats.
AB  - OBJECTIVE: To assess the feasibility of welding everted enterotomies with laser.
      DESIGN: Open study. MATERIAL: 21 Male albino rats (mean weight 152 g).
      INTERVENTIONS: 28 Full thickness enterotomies (involving 50% to complete
      circumference of the rat's small intestine) were welded with an Nd-YAG laser non
      contact fibre. The bowel ends were everted and held tightly with simple non
      toothed forceps during welding. MAIN OUTCOME MEASURE: Success or failure judged
      by the naked eye. RESULTS: Welding was successful in 14/20 (70%) enterotomies
      that involved half the circumference of the small bowel but in only 3/8 (38%)
      when the enterotomy extended further because of inadequate tissue opposition. A
      new visual end point of welding was noticed. CONCLUSION: Laser welding of everted
      enterotomies is safe for small enterotomies as judged by the naked eye, but
      controlled studies are needed before the technique can be tested in humans.

PMID- 8555343
TI  - Prospective evaluation of sutured, continuous, and interrupted single layer
      colonic anastomoses.
AB  - OBJECTIVE: To evaluate the merits of continuous and interrupted colonic
      anastomoses. DESIGN: Prospective non-randomised study. SETTING: District
      hospital, UK. SUBJECTS: 53 Patients (24 male and 29 female) of whom 26 underwent
      continuous and 27 interrupted sutured colonic anastomoses. MAIN OUTCOME MEASURES:
      Mortality at 30 days, time taken to complete anastomosis, anastomotic dehiscence
      and anastomotic stricture. RESULTS: No patient died within 30 days. There were no
      significant differences in (median, range) time taken to complete the anastomosis
      (continuous: 15 (7-23) minutes; interrupted: 26 (10-34) minutes, p = 0.27);
      anastomotic leak rate (continuous 1; interrupted 1) and anastomotic stricture
      (continuous 1 and interrupted 1). Patients were followed up for a mean of 15
      months after continuous and 18 months after interrupted colonic anastomoses.
      CONCLUSION: As both techniques were equally safe, it is probable that the type of
      colonic anastomosis done will remain a matter of individual preference.

PMID- 8555342
TI  - Intestinal mucosal injury during porcine faecal peritonitis.
AB  - OBJECTIVE: To assess the incidence of intestinal mucosal injury during faecal
      peritonitis in pigs, the relation of such lesions to haemodynamic variables,
      intramucosal pH (pHi), and endothelial adherence of polymorphonuclear leucocytes
      (PMNs). DESIGN: Experimental laboratory study. SETTING: University department of
      surgery, Sweden. SUBJECTS: 57 Juvenile pigs. INTERVENTIONS: Pigs had faecal
      peritonitis induced (n = 39) or a sham procedure (n = 18). In addition, 15
      animals were pretreated with the monoclonal CD18 receptor antibody IB4 before
      induction of peritonitis with the aim of preventing tissue accumulation of PMNs.
      MAIN OUTCOME MEASURES: Development of mucosal lesions and correlation with
      haemodynamic variables. RESULTS: 17/18 (94%) of control animals had normal
      mucosa. The incidence of mucosal lesions in animals with faecal peritonitis was
      56%. Animals with severe mucosal injury (grade 4-5) had significantly lower mean
      arterial pressure, cardiac index, and pHi during the last hour of the experiment
      compared with animals without mucosal lesions. Pretreatment with IB4 did not
      prevent the development of intestinal mucosal injuries. Intramucosal pH decreased
      during sepsis and was not affected by IB4. CONCLUSIONS: Severe intestinal mucosal
      injury is associated with arterial hypotension, low cardiac index, and low pH.
      Neither the mucosal injury nor the reduction in pHi seen during porcine faecal
      peritonitis seemed to be leucocyte-related phenomena.

PMID- 8555344
TI  - Cancers among patients diagnosed as having diverticular disease of the colon.
AB  - OBJECTIVE: To assess the incidence of underlying malignancy in patients with a
      diagnosis of diverticular disease of the colon. DESIGN: Retrospective cohort
      study. SETTING: University hospital, Sweden. SUBJECTS: 7159 patients discharged
      from hospital with a first diagnosis of diverticulosis or diverticulitis in
      central Sweden 1965-1983. INTERVENTION: The cohort was followed up for two years
      for the occurrence of cancer. MAIN OUTCOME MEASURE: Cancer incidence. RESULTS: A
      total of 372 cancer cases were identified standard incidence ratio = 2.4; 95%
      confidence interval 2.2 to 2.7). Sites at excess risk during the first year were:
      colon and rectum, pancreas, prostate, stomach, lymphatic and haemopoietic tissue,
      liver and bile ducts, ovary and lung, with the highest excess risk in the left
      colon (standard incidence ratio = 17.8; 95% CI 12.7 to 24.1). CONCLUSION:
      Malignant diseases, especially colorectal cancer, are relatively common among
      patients with a clinical diagnosis of diverticulosis or diverticulitis of the
      colon. This may indicate a need for a change in current clinical practice.

PMID- 8555345
TI  - Abdominoperineal excision of the rectum and anal canal with perineal colostomy.

PMID- 8555346
TI  - Reversed rotation of midgut which caused problems during Whipple's procedure.

PMID- 8555347
TI  - Bleeding pancreatic pseudoaneurysms.

PMID- 8555349
TI  - True aneurysm of the uterine artery.

PMID- 8555348
TI  - Long term survival after obstruction of the common bile duct by ductal
      hepatocellular carcinoma.

PMID- 8555350
TI  - Healing the warrior: admission of two American Indian war-veteran cohort groups
      to a specialized inpatient PTSD unit.
AB  - The American Lake VA Post-Traumatic Stress Disorder (PTSD) Treatment Program
      provides intensive inpatient treatment for war-related PTSD and associated
      conditions. As part of a substantial outreach effort to American Indians (AI) in
      the Northwest U.S., the program significantly modified its admission criteria and
      treatment to be more clinically and culturally relevant. An all-AI cohort, and
      then a group that was 50% AI, were admitted. Highlighted are lessons learned
      regarding: treating "traditional" versus more "assimilated" AI veterans; culture
      specific additions of building and utilizing a sweatlodge on the hospital
      grounds, hiring an AI spiritual leader as a clinical advisor, and promoting
      attendance at weekend Pow-Wows; the relevance of the "regular" treatment
      components; and the need for regular debriefings about counter-transference
      dynamics among staff.

PMID- 8555351
TI  - Multi-dimensional adolescent treatment with American Indians.
AB  - The purpose of this study was to determine the effectiveness of an American
      Indian adolescent treatment program. A two-year follow-up study was conducted
      measuring school performance and antisocial behavior. It was found that American
      Indian adolescents who completed the program tended to have improved school
      performance and less involvement with the criminal justice system.

PMID- 8555352
TI  - How does IHS relate administratively to the high alcoholism mortality rate?
AB  - From 1969 to 1990 the alcoholism mortality rate for American Indians/Alaska
      Natives (AI/AN) has been steadily decreasing. Compared to the U.S. All Races
      overall rate decrease of 7.8% in that time period, the AI/AN rate has decreased
      33.6%, a remarkable fourfold decrease in the mortality rate due to alcoholism. In
      the decade from 1978 to 1988 the rate decreased from 64.5/100,000 in 1978 to
      37.3/100,000 in 1988, a decrease of 42.2%. The comparable figures for U.S. All
      Races were 8.1/100,000 in 1978 and 7.0/100,000 in 1988, a decrease of 13.6%.
      During this decade (1978 to 1988) the Indian Health Service (IHS) embarked upon a
      major effort to assimilate and to expand alcoholism programs then transferred
      from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) by
      incorporating those programs into the IHS health delivery system. The number of
      programs has more than doubled (158/400) since the transfer was completed in
      1983. Funds, moreover, have quadrupled ($20/$82.3 million in 1993). The actual
      funds expended by IHS from Fiscal Year (FY) 1981 through FY 1993 were
      $559,916,000. Despite the dramatic increase in numbers of programs and total
      funds applied to the reduction of alcoholism mortality, available data reveal an
      increase in alcoholism mortality of 40.3% from 1986 to 1990. This article reviews
      and questions the relationship of allocations, per capita expenditures, and
      service components available to reduce alcoholism mortality by IHS Areas in light
      of the increase in the mortality rate and the fourfold increase in the budget.
      The data appear to show little relationship of mortality rate with allocations,
      the number of service components available, or per capita expenditures.

PMID- 8555353
TI  - Social correlates of American Indian suicide and homicide rates.
AB  - The state suicide rates of American Indians in 1980 showed a very different
      pattern of associations with state social variables than did the state suicide
      rates of Whites. In contrast, the homicide rates had similar associations, in
      particular with an index of social instability. The implications of these
      findings for theory are examined, and suggestions made for further research.

PMID- 8555354
TI  - Mental Health Service Deficit: the South Dakota experience.

PMID- 8555355
TI  - [Production and catalytic properties of point mutants Phe41--->His and Phe143--
      >Glu of horseradish peroxidase, expressed in Escherichia coli].
AB  - Recombinant horseradish peroxidase and its single-point mutants, F4IH and H143E,
      have been reactivated from E. coli inclusion bodies with a 25% yield. Both
      mutations affect heme entrapment as well as enzyme stability and activity. A more
      than 40-fold decrease in the specific activity towards ABTS is associated with
      different steps of peroxidase catalysis. F41H replacement results in a drop of
      both rate constants by two and one orders or magnitude for hydrogen peroxide and
      ABTS, respectively. The mechanism of iodide oxidation by the F41H mutant fits
      into a ternary interaction. The F143E replacement mainly affects the steps of
      ABTS oxidation and product dissociation. It is suggested that the role of
      replaced phenylalanine residues consists in the formation of a highly hydrophobic
      pocket allowing for strong non-covalent binding of the heme porphyrin ring.

PMID- 8555356
TI  - [Is oxythiamine an antivitamin?].
AB  - The review deals with biological and medical aspects of oxythiamine biochemistry
      with special reference to the facts which contradict the traditional antivitamin
      conception. Alternatives to the coenzyme mechanism in interpreting the metabolic
      effects of this vitamin B1 derivative are discussed.

PMID- 8555357
TI  - [Proteolytic enzymes and regulation of the level of active neuropeptides].

PMID- 8555358
TI  - [A secreted trypsin-like proteinase from Yersinia pseudotuberculosis].
AB  - A proteolytic enzyme splitting casein and catalyzing the hydrolysis of the ester
      bond in the synthetic substrate, BAEE, in a trypsin-like manner, has been
      isolated from the cultural filtrate of Yersinia pseudotuberculosis using
      ultrafiltration and gel-filtration. The molecular mass of the enzyme is 110 kDa.
      The rate of hydrolysis is proportional to the enzyme and substrate concentrations
      which is typical for the kinetics of enzymatic reactions. The Km value for the Y.
      pseudotuberculosis enzyme is 2.5.10(-3) M. The optimal conditions for the
      enzymatic reaction are as follows: pH 7.4-8.0 (phosphate buffer) and 37 degrees
      C. The enzyme is inhibited by phenylmethylsulfonylfluoride and
      tosyllysinechlormethylketone, the specific inhibitors of serine proteinases and
      trypsin, respectively. These and literary data on bacterial proteinases are
      suggestive of their possible role as major factors in bacterial pathogenicity.

PMID- 8555359
TI  - [Antihemolytic effect of chlorpromazine on erythrocytes in hyperosmotic and cold
      shock].
AB  - The combined effect of preliminary dehydration of erythrocytes and the cationic
      amphiphilic compound, chlorpromazine, on the stability of cells to subsequent
      hyperosmotic effect, has been studied. A protective effect of chlorpromazine
      depending on the degree of initial cell dehydration and temperature was found.
      The results obtained by an addition of the cationic amphiphile at preliminary
      stages of the experiment and directly in the process of development of
      hyperosmotic lysis have been compared. A conclusion was drawn that the observed
      effect is not due to preliminary treatment of cells with chlorpromazine and is
      therefore unrelated to its influence on the regulatory systems of the cell. It
      has been shown also that under cold shock conditions the earlier established
      protective effect of chlorpromazine is also directly realized at the moment of
      stress exposure, i.e., with a change in temperature.

PMID- 8555360
TI  - [Flavin-containing polyaminooxidase in the liver: spectral properties and
      localization].
AB  - Some properties of flavin-containing polyamine oxidase from bovine liver have
      been studied. Limited proteolysis of the enzyme by trypsin resulted in two
      fragments with molecular masses of 48 and 5-8 kDa. The antigenic determinants of
      the protein appear to be bound to the larger proteolytic fragment. The effect of
      proteolysis on optical properties of the enzyme has been established. Data from
      immunological analysis suggest that the soluble fraction of the liver is a rich
      source of the enzyme.

PMID- 8555361
TI  - [Molecular forms of human growth hormone and prolactin, secreted by cultured
      pituitary tumor cells].
AB  - Functionally active cultures of human pituitary adenoma cells producing excessive
      amounts of the growth hormone (somatotropinomas), of prolactin (prolactinomas) or
      of the both hormones (mixed type adenomas) have been prepared and their secreted
      molecular forms studied. SDS-PAAG electrophoresis combined with immunoblotting
      making use of poly- and monoclonal antibodies revealed that the growth hormone
      and prolactin are secreted by adenoma cells in several molecular forms typical of
      normal human pituitary. The major form secreted by the growth hormone is 22K; the
      minor forms are 20K (the product of alternative splicing of pre-mRNA) and the
      split-off two-chain form 25K. The major form secreted by prolactin is 23K; the
      minor form is glycosylated 25K. No significant differences in the ratios of
      molecular forms of the hormones were found either under basal conditions of
      culturing or under the influence of the pituitary function regulators,
      somatostatin and thyroliberin. At the same time, the data obtained suggest that
      pituitary adenoma cells can secrete some amount of "abnormal" molecular forms of
      the hormones, e.g., immature products of postribosomal processing or large-sized
      immunoreactive fragments. Hence, pituitary adenoma cell cultures are an effective
      tool in biochemical and physiological studies of molecular forms of the human
      growth hormone and prolactin and of their secretion.

PMID- 8555362
TI  - [Interaction of metal ions with the carboxyl group of Asp-5 in the active site of
      uridine phosphorylase from Escherichia coli K-12].
AB  - The effects of La3+ ions on enzymatic activity and difference absorption spectra
      of native and fluorescein isothiocyanate (FITC) modified uridine phosphorylase
      from E. coli K-12 have been studied. Excess La3+, unlike Ag+, only slightly
      decreases the enzyme activity but provokes similar changes in the absorption
      spectra of both native and modified proteins. The Kd value for La3+ ions (0.2 mM)
      coincides with that obtained earlier for Ag+. La3+ ions (0.2 mM) have no effect
      on the rate of the enzyme inactivation by diethylpyrocarbonate or
      tetranitromethane but increases the rate of its inactivation by Woodward's
      reagent K (WRK). Binding of La3+ (Kd = 0.2 mM) markedly decreases the thermal
      stability of the enzyme which increases with a further rise in the La3+
      concentration. The values of Kd (0.2 mM) as well as the difference spectra and
      specific interactions with WRK indicate that one of the ligands interacting with
      metal ions is the carboxyl group of the Asp-5 residue. According to X-ray
      analysis data, this residue is involved in the formation of the active center of
      uridine phosphorylase.

PMID- 8555363
TI  - [Calponin inhibits the strong type of myosin binding with actin].
AB  - The effects of calponin on conformational changes in actin caused by modelling of
      "strong" binding between actin and myosin heads have been studied using
      polarization fluorimetry. "Strong" binding was modelled by decoration of thin
      filaments by myosin subfragment I modified by N-ethylmaleimide (NEM-SI) or
      phosphorylated heavy meromyosin (pHMM). Changes in the actin structure were
      followed by orientation and mobility of the fluorescent probe--the rhodamine
      phalloidin complex. It has been found that calponin cooperatively changes the
      actin conformation, the maximal conformational changes in actin thin filaments
      being observed at the calponin/actin molar ratio of about 1:7. The conformational
      changes in actin induced by NEM-SI and pHMM are typical of strong binding.
      Calponin inhibited this effect. It is suggested that the mechanism of calponin
      regulation of smooth muscle contractility is tightly coupled to the inhibition of
      formation of the stage limiting the rate of ATP hydrolysis by actomyosin.

PMID- 8555364
TI  - [The effect of hydrogen peroxide and hypochlorite on brain Na,K-ATPase activity].
AB  - Brain Na,K-ATPase is subjected to direct modifying influence of the hypochlorite
      anion and hydrogen peroxide resulting in irreversible inactivation of the enzyme.
      The K0.5 values for these compounds are 20-40 microM and 1 mM, respectively. The
      inhibiting effect of hydrogen peroxide is suppressed by desferrioxamine (by 20
      30%) which indicates that the H2O2-induced inhibition is partly due to the
      generation of the hydroxyl radical. Carnosine, homocarnosine and the hydrophobic
      antioxidants, alpha-tocopherol and ionol, protect the enzyme from H2O2: their
      effective concentrations are to 10 mM (carnosine), 5 microM (alpha-tocopherol),
      and 0.5 microM (ionol). The data obtained suggest that inhibition of Na,K-ATPase
      by the antioxidants is caused by their direct action on the protein molecule,
      while the protective effect of natural hydrophilic antioxidants are due to the
      quenching of the hydroxyl radical.

PMID- 8555365
TI  - [Isolation and certain properties of human brain glutamine synthetase].
AB  - A new effective procedure for purifying of glutamine synthetase (GS, EC 6.3.1.2)
      from human brain has been developed. The procedure includes homogenization of
      brain tissue, centrifugation, precipitation with (NH4)2SO4, ion-exchange
      chromatography on cellulose DE-32 and CM-32, gel-filtration on Sepharose CL-6B
      and chromatography on AH-Sepharose 4B. On SDS-PAAG electrophoresis purified GS
      gives a single protein band with a molecular mass of about 44 kDa. Two
      dimensional electrophoresis of GS performed according to O'Farrell gives a
      protein spots multiplet (all the spots corresponding to M(r) approximately 44 kDa
      and pI 6.7-7.2), presumably as a result of covalent modification of GS subunits.
      The apparent Km value for L-Glu in the synthetase reaction is 14.3 mM; the Km
      value for L-Gln in the transferase reaction is 18.1 mM. The pH values of 6-7 and
      7.2 were found to be optimal for the transferase and synthase GS activities in
      the imidazole buffer. The optimal concentrations of Mg2+ ions for the synthetase
      and transferase activities of GS were 10 and 15-20 mM, respectively; that of Mn2+
      ions was 1 mM for the both reactions. Some biochemical properties (isoelectric
      point, subunit molecular masses, optimal concentrations of metal ions) differ
      essentially from those of animal GS. Rabbit polyclonal antibodies raised against
      the human brain GS detect GS in human brain homogenates, but not in rat or bovine
      brain homogenates.

PMID- 8555367
TI  - [Fusion of negatively-charged liposomes under the effect of peptides from the N
      terminal fragment of the HIV-1 transmembrane protein].
AB  - The effect of a series of synthetic peptides mimicking the N-terminus of HIV
      transmembrane glycoprotein (gp41) on fusion of negatively charged liposomes
      consisting of phosphatidylcholine, phosphatidylethanolamine and cardiolipin at a
      2:3:5 molar ratio, respectively, has been studied. Peptides P514 and P385
      (residue 517-538), lysine and arginine at the C-terminus, respectively, with the
      amino acid sequence completely corresponding to the N-terminus of gp41 displayed
      the highest fusogenic activity. The extent of fusion was significantly increased
      at mild acidic pH (6.0). Acidification particularly influenced the fusogenic
      activity of P514. Modification of the N- and C-termini of fusion-active peptides
      by proteins and synthetic polymers blocked the fusion activity. The fusogenic
      properties of peptides depended on the chain length: P411 consisting of nine
      hydrophobic amino acid residues had no fusogenic activity, while P415, an 11
      member peptide, effectively fused liposomes. The fluorescent probe ANS was used
      to monitor the hydrophobicity of these peptides. The hydrophobicity of P514
      increased appreciably with a change in pH from 6.0 to 7.5. Peptides P514 and P385
      induced the leakage of the aqueous contents from liposomes at neutral pH and
      caused a small, but detectable leakage at acidic pH. Structural and molecular
      factors influencing the peptide-induced liposome fusion are discussed.

PMID- 8555366
TI  - [The effect of p-chloromercuribenzoate on regulation of oxidative phosphorylation
      by ADP and ATP and stimulation of liver mitochondrial respiration by palmitate].
AB  - The effect of p-chloromercuribenzoate (pCMB) on oxidative phosphorylation and
      palmitate-stimulated respiration of liver mitochondria has been studied. pCMB (1
      microM) does not affect oxidative phosphorylation but reduces the inhibiting
      effect of ATP on this process. Used at the same concentration, pCMB eliminates
      the inhibiting effect of ADP and ATP on mitochondrial respiration in the presence
      of 10 and 20 microM palmitate. pCMB has no effect on inhibition of oxidative
      phosphorylation by carboxyatractyloside or on palmitate-stimulated respiration of
      mitochondria. It is concluded that the SH-groups of mitochondria localized in the
      hydrophilic region outside the inner mitochondrial membrane participate in
      regulation of oxidative phosphorylation by ATP and in regulation of palmitate
      stimulated respiration by ADP + ATP.

PMID- 8555368
TI  - [Preparative isolation of proteins from 30S ribosomal subparticles from Thermus
      thermophilus under nondenaturing conditions].
AB  - A procedure for isolation in preparative amounts of 15 individual proteins from
      ribosomal 30S subparticles of Thermus thermophilus under non-denaturing
      conditions, has been developed. The amino acid composition and molecular masses
      of the proteins have been determined and the UV absorption spectra and extinction
      coefficients measured. A homology of 13 proteins to corresponding ribosomal
      proteins of E. coli has been established.

PMID- 8555369
TI  - [How many proteins can be designated by the term "chordin"?].

PMID- 8555370
TI  - Labelling DNA strand breaks with BrdUTP. Detection of apoptosis and cell
      proliferation.
AB  - In situ presence of numerous DNA strand breaks is a typical feature of apoptotic
      cells. Selective DNA strand break induction by photolysis (SBIP) at sites that
      contain incorporated halogenated DNA precursors has recently been proposed as a
      method of analysing DNA replication. Detection of DNA strand breaks, thus,
      enables one to identify apoptotic and/or DNA replicating cells. The current
      methods for DNA strand break labelling rely on the use of exogenous terminal
      deoxynucleotidyl transferase which either directly attaches the fluorochrome
      conjugated triphosphodeoxynucleotides to 3'OH ends in the breaks, or indirectly
      labels 3'OH ends with digoxygenin or biotin conjugated
      triphosphodeoxynucleotides. A limitation of these methodologies, especially
      restricting their routine application in the clinic, is high cost of reagents. In
      the present study we have tested whether relatively simple compound BrdUTP, which
      is approximately three orders of magnitude less expensive than dUTP conjugated to
      digoxygenin, can be used as marker of DNA strand breaks. Apoptosis of HL-60 cells
      was induced by DNA topoisomerase I inhibitor camptothecin. The incorporated
      BrdUTP was detected by fluoresceinated anti-BrdUrd MoAb. Cellular fluorescence
      was measured by flow cytometry as well as by Laser Scanning Cytometer (LSC). The
      data show that intensity of DNA strand break labelling with BrdUTP was nearly
      four- and two-fold higher than that obtained with the indirect labelling using
      biotin- or digoxygenin-conjugated dUTP, respectively, and over eight-fold higher
      than in the case of direct labelling with the fluorochrome (fluorescein or
      BODIPY)-conjugated deoxynucleotides. The increased labelling of DNA strand breaks
      with BrdUTP may reflect more efficient incorporation of this precursor by
      terminal transferase, compared to the nucleotides with bulky fluorochrome
      conjugates. DNA strand break labelling with BrdUTP, thus, offers a possibility of
      more sensitive (and at lower cost) detection of apoptotic or DNA replicating
      cells, compared to the alternative methods of DNA strand break labelling.

PMID- 8555371
TI  - Effects of IL-11 on the growth of intestinal epithelial cells in vitro.
AB  - The network of interacting factors that control proliferation in the intestinal
      epithelium is largely unknown. Recently, IL-11 was found to protect animals from
      lethal doses of cytotoxic agents. Part of this protective action was ascribed to
      a reduced level of damage in the intestinal epithelium. Whether this was due to a
      direct effect on epithelial cell cycle progression was unclear. We have addressed
      this question in vitro and found that IL-11 reversibly inhibited proliferation in
      untransformed small intestinal IEC18 cells. However, IL-11 did not inhibit
      transformed SW620 or HT29 colonic cell lines. IL-6 behaved in a similar manner to
      IL-11. Thus, these results suggest that IL-11 may be an ideal therapy adjuvant,
      protecting normal cells and further, these results suggest that IL-11 may be
      involved in the normal growth controls in the intestinal epithelium. The
      inhibitory response evoked by IL-11 is lost during carcinogenic transformation.

PMID- 8555372
TI  - Cell proliferation in the subependymal layer of the adult mouse in vivo and in
      vitro.
AB  - Pulse labelling experiments with [3H] thymidine (dT) and double labelling
      experiments with [3H]dT and bromodeoxyuridine (BrdUrd) were carried out on cells
      of the subependymal layer in the brain of adult normal mice in vivo, in vivo/in
      vitro and in vitro. The results should (i) lead to information about cell cycle
      parameters of these cells in the brain of adult mice, since these cells have been
      studied mostly in the rat brain up to now and (ii) answer the question whether
      results concerning cell proliferation obtained in vivo correspond with those from
      brain slices incubated in vitro with or without prelabelling in vivo. In vivo an
      LI of 20.2 +/- 2.7% (mean +/- SEM) and Ts = 7.2 +/- 0.7 h were found.
      Furthermore, grain count halving experiments led to a surprisingly short cycle
      time (Tc) of 11.2-14.2 h. The longer Tc values (18-20 h) reported in the
      literature for subependymal cells in the rat brain seem to be due to evaluations
      of different areas around the lateral ventricle without considering the migrating
      behaviour of these cells which is quite different regionally. The in vitro
      studies (with or without prelabelling in vivo) showed a significantly reduced LI
      due to the fact that about 20% of the S phase cells, possibly lying in the middle
      of S, stopped further DNA synthesis after transfer to culture. This was shown by
      comparing the cell fluxes at the G1/S and S/G2 borders of in vivo vs. in vitro
      studies.

PMID- 8555373
TI  - In vitro bromodeoxyuridine-labelling of single cell suspensions: effects of time
      and temperature of sample storage.
AB  - The present study was aimed to explore how the in vitro BrdUrd-labelling of rat
      thymocytes might be affected by both the time elapsed between obtaining the
      sample and the beginning of the labelling (0, 15, 30 or 60 min) and the effect of
      the temperature of storage (4 degrees C versus room temperature). Single cell
      suspensions obtained after in vivo labelling with BrdUrd were used as controls.
      The S phase fraction was calculated by flow cytometry both according to BrdUrd
      immunolabelling and DNA content. Immediate incubation with BrdUrd after the
      sample was obtained resulted in a slight decrease of the proportion of S phase
      cells analysed either according to DNA content or to BrdUrd-immunolabelling.
      Regardless of storage-temperature, the S phase fraction decreased in samples kept
      for 15 min or more before BrdUrd incubation. No BrdUrd-positive cells were
      detected in samples stored for 60 min at room temperature. This effect was
      related to temperature since positive cells were found when the samples were kept
      at 4 degrees C during the same time period. Our results suggest that during in
      vitro incubation a relative loss of S phase cells exists and that a delay beyond
      15 min between obtaining the sample and the in vitro labelling seriously
      compromises the results of this technique.

PMID- 8555374
TI  - Effect of melphalan and hyperthermia on cell cycle progression and cyclin B1
      expression in human melanoma cells.
AB  - We have investigated the effect of mild hyperthermia (42 degrees C) on the
      cytotoxic activity of a 1 h melphalan exposure in human melanoma cell lines.
      Hyperthermia did not affect cell growth of any culture, but it increased, to a
      different extent, melphalan cytotoxicity in all cell lines, with a reduction in
      the IC50 of 1.7 to 2.6-fold. Flow cytometric analysis showed that in normal
      temperature conditions melphalan caused S phase cell accumulation, which was
      evident only at 24 h in JR8, M14 and 2/21 cell lines and was still persistent at
      72 h in 2/60 cells. Moreover, in all cell lines, the delay in S phase was
      paralleled, or followed, by an accumulation of cells in G2+M, which was transient
      in JR8 and M14 cells and persisted until 72 h in 2/21 and 2/60 melanoma clones.
      Hyperthermia caused a stabilization and prolongation of melphalan induced G2+M
      accumulation in JR8 and M14 cells. Conversely, in 2/21 and 2/60 clones, cell
      cycle perturbations induced by the drug were similar under normothermic or
      hyperthermic conditions. Specifically, in JR8, for which the maximum enhancement
      by hyperthermia on melphalan cytotoxicity was observed, cell accumulation in G2+M
      was still present 120 h after treatment. The accumulation was accompanied by an
      inhibition in the G2-M transition, as demonstrated by the significant reduction
      in the mitotic index of cells exposed to combined treatment compared to controls.
      Moreover, a bivariate distribution of cells stained for DNA and cyclin B1 showed
      that, following melphalan and hyperthermia treatment, the fraction of cyclin B1
      expressing cells paralleled the fraction of G2+M phase cells, thus indicating
      that the inability of cells to enter mitosis was not ascribable to a reduction of
      cyclin B1 expression. On the whole, our results indicate that hyperthermia can
      stabilize the G2 accumulation induced by melphalan in human melanoma cells. Such
      a stabilization could contribute to the enhancement of melphalan cytotoxicity by
      heat, even though a strict correlation was not observed between the magnitude and
      persistence of the cell cycle perturbations and the extent of melphalan activity.

PMID- 8555375
TI  - Plasma homovanillic acid levels and therapeutic outcome in schizophrenics:
      comparisons of neuroleptic-naive first-episode patients and patients with disease
      exacerbation due to neuroleptic discontinuance.
AB  - Plasma homovanillic acid (pHVA) levels were measured and the Brief Psychiatric
      Rating Scale (BPRS) scores were evaluated in 26 schizophrenic patients who had
      either never been medicated (neuroleptic-naive, first-episode subjects) or whose
      condition had become exacerbated following neuroleptic discontinuance
      (exacerbated subjects). All the subjects received medication with a fixed dose of
      a neuroleptic (haloperidol or fluphenazine, both 9 mg/day) for the first week and
      variable doses for the subsequent 4 weeks. In the neuroleptic-naive subjects,
      pHVA levels increased significantly 1 week after starting the protocol; this
      increase correlated significantly with clinical improvement of the BPRS positive
      symptom scores at week 5. In the neuroleptic-naive subjects, pHVA levels had
      declined to the baseline level by week 5. In the exacerbated subjects, there were
      no significant correlations between pHVA level changes at week 1 and later
      improvements of the BPRS positive symptom scores. These results suggest that the
      rise in pHVA levels occurring within 1 week after starting a fixed neuroleptic
      dose may predict a favorable clinical response in neuroleptic-naive schizophrenic
      patients.

PMID- 8555376
TI  - Age at onset of geriatric depression and sensorineural hearing deficits.
AB  - Comorbidity of sensorineural hearing deficits and both depressive states and
      dementia in late life provided the rationale for this investigation. Cognitively
      intact geriatric major depressives (n = 43) were assessed for depressive
      symptoms, cognitive performance, and delusions while symptomatic, and following
      treatment, when audiometry was performed. Late-onset depressed patients (LOD) had
      more hearing deficits compared to early-onset depressives (EOD). Age at onset of
      depression was found to have a significant effect on Pure-Tone Thresholds for 0.5
      4.0 kHz and on Word Recognition in Noise in the better ear (0.001 < p < 0.031;
      ANCOVA). Criteria for neural deficit were met more frequently in LODs compared to
      EODs, although this was attributable to the older age of LOD. Additional
      investigations can contribute to our understanding of the relationship between
      forms of hearing loss and both the course of geriatric depression and its
      relationship to dementia.

PMID- 8555377
TI  - Plasma amino acid ratios related to brain serotonin synthesis in response to food
      intake in bulimia nervosa.
AB  - Fifteen bulimic women (BN) and 19 healthy female controls (CO) were studied. The
      subjects were cross-over treated with either fluoxetine (FXT) or placebo during 4
      days. They received, in randomized order, a breakfast containing pure
      carbohydrate (CHO) or a protein-rich (PROT) breakfast following day 3 and 4 of
      each treatment period. Twenty-nine different food items were offered for lunch.
      The fasting serum glucose and insulin concentrations and the fasting plasma
      tryptophan (Trp)/large neutral amino acid (LNAA) ratio were slightly higher in
      BN. The changes of these metabolic parameters in response to a CHO or PROT
      breakfast were similar in both groups. Across breakfast type, the plasma
      (Trp)/(LNAA) ratio at 120 min after breakfast was higher in BN. Total caloric
      intake at lunchtime was less in BN. In CO, less carbohydrate was selected at
      lunchtime following the CHO breakfast, an effect that was abolished by FXT.
      Breakfast type or FXT did not have any apparent effect on food intake at
      lunchtime in BN. This might indicate that bulimic subjects are less sensitive to
      serotoninergic stimuli than control subjects.

PMID- 8555378
TI  - L-DOPA and psychosis: evidence for L-DOPA-induced increases in prefrontal cortex
      dopamine and in serum corticosterone.
AB  - L-DOPA can often induce psychotic reactions during treatment for Parkinson's
      disease. This study was undertaken to assess, in an animal model of Parkinson's
      disease, the impact of L-DOPA treatment on two potential biological risk factors
      for psychosis, namely, an increase in prefrontal cortex dopamine and an increase
      in the stress-related hormone corticosterone. Hemiparkinsonian rats with
      unilateral 6-hydroxydopamine (6-OHDA) lesions which resulted in severe unilateral
      denervation of dopamine neurons were treated with either saline or 25 mg/kg L
      DOPA methyl ester (with 2 mg/kg carbidopa). Serum L-DOPA concentrations were
      found to be positively and highly correlated with serum corticosterone, with
      medial prefrontal cortex dopamine and with the dopamine metabolite homovanillic
      acid. Serum L-DOPA, however, was found not to be correlated with serum or brain
      concentrations of serotonin, 5-hydroxyindoleacetic acid, or norepinephrine. These
      findings support the possibility that chronic L-DOPA treatment can expose
      parkinsonian patients to two significant risk factors for psychosis: 1) increased
      levels of prefrontal cortex dopamine, and 2) increased levels of serum
      corticosterone.

PMID- 8555379
TI  - Quantified electroencephalographic changes in depressed patients with and without
      dementia.
AB  - We carried out quantified electroencephalograms (qEEG) in 17 patients with
      probable Alzheimer's disease (AD), who also met the DSM-III-R criteria for either
      dysthymia or major depression, and 18 AD patients with comparable intellectual
      impairment but no depression, 13 patients with depression but no AD, and 10 age
      matched normal controls. There was a significant effect for depression in alpha
      relative power: depressed patients (with or without AD) showed a significantly
      lower alpha relative power in the right posterior region as compared to
      nondepressed patients; however, this change was observed over the right
      hemisphere in depressed non-AD patients, and in left, medial, and right posterior
      regions in depressed-AD patients. Depressed patients without AD showed a
      significant global decrease in delta power, whereas depressed patients with AD
      showed significant increments in delta power in posterior brain areas. In
      conclusion, AD patients with depression showed qEEG changes that were
      significantly different from qEEG changes in depressed non-AD patients.

PMID- 8555380
TI  - Ambulatory monitoring of panic patients during regular activity: a preliminary
      report.
AB  - Ten patients with panic disorder and 10 matched control subjects were compared as
      to their blood pressure and heart rate during regular daily activity.
      Physiological responses were monitored by ambulatory recorder, and subjective
      reports of mood were collected. Data were analyzed controlling for activity and
      stress level of the subjects. Diastolic blood pressure emerged as a possible
      discriminatory factor between the groups. A trend for higher heart rate occurred
      in the panic group. In behavioral terms, panic patients tended to avoid anxiety
      provoking situations, resulting in anxiety ratings comparable to those of the
      control group. Thus, recorded physiological differences between the groups may
      reflect heightened baseline autonomic activity in panic patients.

PMID- 8555381
TI  - Sleep during clozapine-induced fever in a schizophrenic patient.

PMID- 8555382
TI  - Discontinuation reactions following sertraline.

PMID- 8555383
TI  - Brain fluoxetine measurements using fluorine magnetic resonance spectroscopy in
      patients with social phobia.

PMID- 8555384
TI  - The serotonin transporter in depressed patients: a qualitative study based on
      dissociation kinetics.

PMID- 8555385
TI  - Gonadotropin response to naloxone challenge in female and male psychotic
      patients: a pilot study.

PMID- 8555386
TI  - Increased serum gamma-aminobutyric acid (GABA) levels in young men at high-risk
      for alcoholism.

PMID- 8555387
TI  - [From informatics as an obstacle to informatics as an excuse: looking towards the
      future].

PMID- 8555388
TI  - [Carpal tunnel syndrome: an occupational disease?].

PMID- 8555389
TI  - [Prevalence of psychopathology at a primary care center].
AB  - OBJECTIVES: To determine the prevalence of psychopathology among those attending
      a primary care centre and discover its diagnostic distribution using the criteria
      of the DSM-III-R. DESIGN: A crossover study of the prevalence of psychopathology.
      A two-phase study was performed by systematic sampling of one of every four
      visits. In the first phase the GHQ-28 was used. For those with suspected
      psychopathology (cut-off point 5/6) a semi-structured interview, Goldberg's CIS,
      was performed. They were assigned a diagnosis from the DSM-III-R. SETTING:
      Maluquer Salvador Health Centre, Girona. PATIENTS: A sample of 400 patients
      between 15 and 65 who attended the Centre for any reason. There were only 2.9%
      losses (2.1% in the first phase and 0.8% in the second). MEASUREMENTS AND MAIN
      RESULTS: Overall prevalence of psychopathology was 38.8% (Cl 34.05-43.55), with
      depression accounting for 10.3% (major depression 6% and dysthymia 4.3%), anxiety
      13.8% (generalised 7.3%, panic 3% and obsessive/compulsive 3%) and adaptive
      disorder 9.5%. CONCLUSIONS: One of every three patients attending a health centre
      suffers from some kind of psychiatric disorder.

PMID- 8555390
TI  - [Use of primary care services by adolescents and detection of health problems
      other than those for which they came].
AB  - OBJECTIVES: To detect in young people requesting Primary Care treatment the
      presence of hidden health problems common to this age-group and to evaluate the
      factors which may affect their being rarely mentioned. DESIGN: Descriptive study.
      PARTICIPANTS: Young people between 14 and 19 who attended two clinics at the Pola
      de Lena Health Centre from April to July 1994. The survey, using a personal
      interview, was aimed at the detection of acne, obesity, oral contraceptives,
      alcohol consumption and depressive disorders. MEASUREMENTS AND MAIN RESULTS: 138
      young people (57 male and 81 female), with an average age of 16, requested care.
      74.4% attended the consultation in company, although in 62.4% of cases the
      initiative was their own. The most common consultation was for acute infectious
      conditions (40.6%). 108 young people (78.3%) were interviewed, with 60 cases of
      acne, 25 of obesity and 28 possible depressive disorders being detected. We
      detected no cases of alcoholism or of uncontrolled oral contraception. For 64.3%
      of these problems, they had never consulted the doctor: they had consulted least
      for depressive disorders (3.6%). The commonest alleged reasons for not consulting
      were not being aware of the problem, indifference, ignorance of the condition's
      risks and consequences or of the existence of effective treatment. CONCLUSIONS:
      There are health problems of some importance about which young people requesting
      care do not consult. These problems should be actively detected and tackled,
      taking advantage of young people's attendance at the Health Centre for other
      reasons.

PMID- 8555391
TI  - [Prevalence of hepatitis B and risk factors as motivation for vaccination
      campaign among adolescents].
AB  - OBJECTIVES: To study the prevalence of viral Hepatitis B infection (VHB) among
      eighth-year EGB (basic) students; associated risk factors; and the prevalence of
      Hepatitis C (HC). DESIGN: A descriptive crossover study. SETTING: Eighth-year EGB
      students from 8 schools in Villaverde-Usera (Madrid). PARTICIPANTS: A sample of
      262 individuals was used to calculate the prevalence of VHB infection (prevalence
      defined at 1.5%, precision = 0.015, confidence at 95% and 5% loss). MEASUREMENTS
      AND MAIN RESULTS: Variables were age, gender, alcohol, tattoos, drugs, family
      history of drugs, Hepatitis, exchanging syringes, razors, syringes, sexual
      relations, history of transfusions or surgery. These were obtained from a
      questionnaire filled in by the students themselves. The definitions were: chronic
      HB carrier: AgHBS+ in the blood; VHB infection: anti-HBc and/or anti-HBs
      positives; VHC infection: presence of anti-HC. 402 children answered the
      questionnaire. Serology was tested in 263 before the vaccination. Average age was
      13.3 +/- 0.69. There were 52.8% males and 47.2% females. Prevalence of VHB
      infection was 2.28% (CI = 0.93-5.14), 6 cases. Prevalence of carriers was 0.38%
      (CI = 0.02-2.43; one case). There were no VHC positives. No links between VHB and
      risk practices could be demonstrated. CONCLUSIONS: 1) Low prevalence of VHB
      infection 2) The zero prevalence of VHC infection is lower than that in healthy
      donors.

PMID- 8555392
TI  - [Consultation by third parties in primary care of the aged].
AB  - OBJECTIVE: To assess elderly persons' consultations by third parties, examine the
      elderly, to know the characteristics of those who use it exclusively and to
      compare their utilization of health services with the utilization by other
      elderly users of Primary Care. DESIGN: Cross sectional study. PATIENTS: Data are
      from a stratified sample of the elderly. SETTING: Leganes. MEASUREMENTS AND MAIN
      RESULTS: Associations between sociodemographic and health variables with
      consultations by third parties are identified. Odds ratios are estimated with a
      logistic regression model fitted to the subsample of primary care users.
      Consultation by third parties is frequent among elderly in Leganes: 24.4% of them
      have used it in the last year; 4.2% exclusively and 20% in combination with other
      forms of general practitioner' consultations. Those consulting exclusively
      through third parties tend to have functional limitations, depression, and
      disabilities which keeps them apart from society. Family members are intermediary
      between elderly and General Practitioner. CONCLUSION: Consultation by third
      parties can lead to diminished quality of care. People who are currently
      consulting through third parties could be eligible to social and health care
      programs.

PMID- 8555393
TI  - [Symptoms related to the use of agricultural pesticides. The perspective from the
      primary care service].
AB  - OBJECTIVE: To find whether agricultural workers seen in the general medical
      clinic attend due to symptoms connected with the use of pesticides. DESIGN: A
      crossover descriptive study comparing agricultural workers with a control group.
      SETTING: Primary care. PARTICIPANTS: The clinical histories of 40 agricultural
      workers and a control group (sample of 58 paired for age and gender) who had been
      seen over the previous year. MEASUREMENTS AND MAIN RESULTS: Age, gender,
      frequency of attendance, motives for consultation, risk factors and the number of
      consultations for symptoms possibly due to exposure to pesticides--in line with a
      previously composed list. There were no differences in frequency of attendance,
      overall reasons for consultation or risk factors. It was seen that agricultural
      workers consulted 4 times more than the control group for suspected pesticide
      poisoning (p = 0.0015). CONCLUSIONS: In our health area agricultural workers
      present symptoms which should probably be attributed to insufficient protection
      against pesticides. The primary care doctor working in rural zones where these
      products are heavily used must be able to identify these symptoms and take
      appropriate measures.

PMID- 8555394
TI  - [Evaluation of the nutritional status of a rural child population in a Valencia
      community: the Pego study].
AB  - OBJECTIVE: To evaluate the nutritional state of the child population of Pego
      (Alicante) in order to define the patterns of normality and check the validity of
      the anthropometric parameters most commonly used in evaluating nutritional
      status. DESIGN: A descriptive crossover study. SETTING: Valls de Pego Primary
      Care Health Centre. PATIENTS: 943 healthy children and adolescents aged 0 to 17
      were studied out of a target population of 2,150 who were seen for treatment at
      the Health Centre for reasons which had nothing to do with nutritional problems.
      INTERVENTIONS: Between july 1989 and december 1990, a simple anthropometric
      assessment of each patient was carried out: obtaining weight, height, the
      nutrition or Shukla index and the Quetelet index. MAIN RESULTS: Nutritional
      distribution was clearly displaced towards high values on the nutritional scale,
      with 14% obesity and 15% overweight as against 13% at risk of malnutrition. There
      was more overweight and obesity at a higher age and in males. CONCLUSIONS: This
      prevalence of nutritional disturbances is similar to that in other Spanish
      studies and confirms both the size of the problem of obesity in the prevention of
      related pathologies in adults and the relevance of the adult's Nutritional
      History throughout his/her life. The study made clear the good correlation and
      utility of the Shukla and Quetelet indexes.

PMID- 8555396
TI  - [Children's accidents treated at health centers].
AB  - OBJECTIVES: To find the characteristics of accidents to children treated at our
      Health Centres. DESIGN: A descriptive crossover study. SETTING: Almanjayar and
      Cartuja Health Centres, Granada. PATIENTS: The 0 to 14 age-group treated at our
      centres because of an accident. MEASUREMENTS AND MAIN RESULTS: The number of
      accidents to children treated at our health centres during 1994 was 217. The most
      common accidents were, in descending order: falls, 27%; burns, 20.7%; traffic
      accidents, 17%; poisoning, 15%; inhalation of foreign bodies, 10.5%; bites and
      aggressions, 9.2%. 48.3% of the accidents occurred at home, 37.7% in the street
      and 13.8% at school. In the relation of type of accident to age group, we found
      that burns affected children under 5 to a greater extent. Poisoning was more
      common between 5 and 9. Traffic accidents and falls affected children between 10
      and 14 more. The relationship between age and type of accident is significant (p
      < 0.005). There is no significant connection between gender and type of accident.
      CONCLUSIONS: Age and some types of accident are directly related. The majority of
      accidents tend to occur at home and in the street. We consider that prevention is
      the best way of decreasing accidents to children. Programmes involving children,
      parents and teachers should be set up.

PMID- 8555397
TI  - [Episode: concept and usefulness in primary care].

PMID- 8555398
TI  - [Backache and work disability: epidemiology and prevention].

PMID- 8555395
TI  - [Hospital-based evaluation of knowledge about their illness in a diabetic
      population].
AB  - OBJECTIVE: To evaluate a group of diabetics' understanding of their illness, both
      generally and in detail in various ways. Their understanding was also assessed in
      relation to gender, age, educational level, the type and length of evolution of
      their diabetes mellitus and what sort of diabetes training they had received.
      DESIGN: The study was observational. A questionnaire completed at a personal
      interview was used to collect data. SETTING: Hospital out-patient endocrinology
      clinics. PATIENTS AND OTHER PARTICIPANTS: 520 diabetics who attended out-patient
      clinics were selected. 35 were excluded because of auditory, linguistic or
      psychological problems. One patient refused to take part. MEASUREMENTS AND MAIN
      RESULTS: Sufficient understanding was observed only in the area concerning
      "glucose in the blood" (79.08% of right answers). With the exception of the
      length of the illness, a certain relationship between patients' understanding
      (both in determined areas and in general) and the rest of the variables was
      revealed. CONCLUSIONS: Except for understanding about the level of "glucose in
      the blood" important educational deficiencies in the group under study were
      detected. This showed the need to prioritise improvements in diabetes training,
      so that patients can better monitor their condition.

PMID- 8555399
TI  - [Chronic fatigue syndrome].

PMID- 8555400
TI  - [The importance of evaluating an anti-influenza campaign].

PMID- 8555401
TI  - [A focal group technique as a tool for evaluating a failed research project].

PMID- 8555402
TI  - [Referral from primary care to hospital emergency services].

PMID- 8555403
TI  - Identification of cis-2-butene-1,4-dial as a microsomal metabolite of furan.
AB  - The hepatocarcinogen furan is believed to be activated to the reactive aldehyde,
      cis-2-butene-1,4-dial, by microsomal enzymes. The rat liver microsomal metabolism
      of furan was examined in the presence of NADPH and semicarbazide. HPLC analysis
      of incubation mixtures revealed the formation of a metabolite that coeluted with
      standards for the bis-semicarbazone adduct of cis-2-butene-1,4-dial. The
      formation of this compound required the presence of NADPH, semicarbazide, and
      microsomes. Preparative isolation and chemical characterization of this
      metabolite confirmed the structural assignment. These data provide evidence that
      the reactive aldehyde, cis-2-butene-1,4-dial, is a major metabolic product of
      furan.

PMID- 8555404
TI  - Fourier-transform ion cyclotron resonance mass spectrometric evidence for the
      formation of alpha-chloroenethiolates and thioketenes from chloroalkene-derived,
      cytotoxic 4-thiaalkanoates.
AB  - The cytotoxicity of chloroalkene-derived cysteine S-conjugates is thought to be
      associated with the formation of alpha-chloroenethiolates and thioketenes as
      reactive intermediates. Recent studies indicate that the formation of 1,2
      dichloroethenethiolate, which may give rise to chlorothioketene, is a key step in
      the bioactivation of 5,6-dichloro-4-thia-5-hexenoic acid (Fitzsimmons et al.
      (1995) Biochemistry 34, 4276-4286). We report here the use of Fourier-transform
      ion cyclotron resonance mass spectrometry to provide the first direct evidence
      for the formation of alpha-chloroenethiolate and thioketene species from a
      cytotoxic 4-thiaalkanoate. The bioactivation of 5,6-dichloro-4-thia-5-hexenoic
      acid involves conversion to the corresponding CoA thioester 5,6-dichloro-4-thia-5
      hexenoyl-CoA and subsequent processing by the fatty acid beta-oxidation pathway.
      It has been proposed that the bioactivation of 5,6-dichloro-4-thia-5-hexenoyl-CoA
      involves loss of 1,2-dichloroethenethiolate, followed by loss of chloride to form
      chlorothioketene. 1,2-Dichloroethenethiolate and related alpha
      chloroalkenethiolates have not been observed directly in aqueous solution.
      Fourier-transform ion cyclotron resonance mass spectrometric experiments show
      that S-propyl 5,6-dichloro-4-thia-5-hexenethioate reacts in the gas phase with
      base (hydroxide ion) to release 1,2-dichloroethenethiolate, which is observed
      directly in the mass spectrum of the products of the gas-phase reaction.
      Furthermore, the elimination of chloride from 1,2-dichloroethenethiolate on
      collision-induced decomposition is facile and provides evidence for
      chlorothioketene formation. Preliminary evidence for the formation of 1,2
      dichloroethenethiolate and chlorothioketene from S-(1,2-dichlorovinyl)-N-acetyl-L
      cysteine methyl ester was also obtained. These observations support the
      intermediacy of alpha-chloroenethiolates and chlorothioketenes in the
      bioactivation of cytotoxic, chloroalkene-derived 4-thiaalkanoates and cysteine S
      conjugates and demonstrate the utility of Fourier-transform ion cyclotron mass
      spectrometry in studying the formation of reactive intermediates.

PMID- 8555405
TI  - Biotransformation of 3-(phenylamino)-1,2-propanediol to 3-(phenylamino)alanine: a
      chemical link between toxic oil syndrome and eosinophilia-myalgia syndrome.
AB  - During late 1989, the eosinophilia-myalgia syndrome (EMS) developed as an
      epidemic in the United States, with numerous additional cases reported in several
      other countries worldwide. Eight years earlier, a closely-related disease, the
      toxic oil syndrome (TOS), occurred in Spain as a massive food-borne epidemic.
      Although EMS was linked to the ingestion of tainted L-tryptophan, and TOS to
      aniline-denatured rapeseed oil, the etiologic agent(s) responsible for both
      diseases remains undetermined. Contaminants in these foodstuffs are believed to
      have triggered the diseases. Aniline contaminants, including 3-(phenylamino)-1,2
      propanediol (PAP), have been reported in oil used by patients who developed TOS.
      A related aniline derivative, 3-(phenylamino)-L-alanine (PAA), was recently
      isolated from L-tryptophan associated with the onset of EMS. Here, we demonstrate
      the biotransformation of PAP into PAA by both rat hepatocytes and human liver
      tissue. The structural characterization of PAA was unequivocally determined using
      on-line HPLC coupled with atmospheric pressure chemical ionization tandem mass
      spectrometry (LC-APCI-MS/MS). This finding is the first reported chemical link
      between TOS and EMS and suggests that these two related diseases share a common
      etiology, namely, PAA.

PMID- 8555407
TI  - Gamma irradiation of 2'-deoxyadenosine in oxygen-free aqueous solutions:
      identification and conformational features of formamidopyrimidine nucleoside
      derivatives.
AB  - The two major radiation-induced decomposition products of 2'-deoxyadenosine in
      oxygen-free aqueous solution have been isolated by reverse-phase HPLC. The 1H and
      13C NMR features of the two modified nucleosides obtained in DMSO-d6 are
      indicative of a similar formamidopyrimidine structure for the base residue (the
      ring-opened form of a C-8 hydroxylated purine). Interestingly, the sugar moiety
      exhibits a pyranose configuration, the two nucleosides being a pair of alpha and
      beta anomers. One-bond and long-range 1H-13C 2D NMR experiments have allowed the
      complete assignment of the carbon atoms. Confirmation of the base structure was
      obtained by 1H-15N scalar-correlated 2D NMR experiments. Attempts were made to
      characterize the expected furanose form of the initially generated
      formamidopyrimidine derivative. In this respect, isomerization reaction of the
      sugar moiety of the latter compound takes place rapidly after gamma-irradiation
      as inferred from 1H NMR analysis. The conformational study of the sugar moiety of
      the two pyranose anomers was inferred from detailed 600.13 MHz 1H NMR analysis in
      D2O. The alpha anomer exhibits a predominant 1C4 conformation whereas the beta
      anomer adopts preferentially a 4C1 conformation. In addition, the dynamic study
      of the restricted rotation of the formamido bond has revealed a 1/5 ratio in
      favor of the s-cis rotamer for both nucleosides. The energy barrier at
      coalescence was determined to be delta G# = 75.5 kJ.mol-1 (Tc = 370 K).

PMID- 8555406
TI  - The sulfoxidation of the hexachlorobutadiene metabolite N-acetyl-S-(1,2,3,4,4
      pentachlorobutadienyl)-L-cysteine is catalyzed by human cytochrome P450 3A
      enzymes.
AB  - The sulfoxidation of the mercapturic acid N-acetyl-S-(1,2,3,4,4-pentachlorobuta
      1,3-dienyl)-L-cysteine (N-Ac-PCBC), a urinary metabolite of the renal toxin
      hexachlorobutadiene (HCBD), was studied in human liver microsomes and with
      purified cDNA expressed human liver cytochrome P450 (P450) enzymes. N-Acetyl-S
      (1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine sulfoxide (N-Ac-PCBC SO) is a
      major urinary metabolite of HCBD in male rats; only liver microsomes from male
      rats catalyze the sulfoxidation of N-Ac-PCBC. Our results presented here show
      that human liver microsomes from both male and female donors are capable of
      oxidizing N-Ac-PCBC to the corresponding sulfoxide diastereomers. The correlation
      of N-Ac-PCBC sulfoxidation with the rates of oxidation of P450 enzyme specific
      substrates suggests that only P450 3A enzymes oxidize N-Ac-PCBC. Moreover, only
      gestodene and troleandomycin, two selective inhibitors for P450 of the 3A family,
      significantly reduced the rates of N-Ac-PCBC sulfoxidation. No reduction in
      sulfoxidation rates was observed with inhibitors for other P450 enzymes, i.e.,
      diethyldithiocarbamate, 4-methylpyrazole, 7,8-benzoflavone, or sulfaphenazole.
      Incubations of N-Ac-PCBC with purified and reconstituted recombinant P450s 1A2,
      2E1, 3A4, and 3A5 resulted in sulfoxide formation only with P450s 3A4 and 3A5. In
      summary, these results indicate that P450 from the 3A family may sulfoxidize N-Ac
      PCBC. Since these P450 enzymes account for a major fraction of the P450 in human
      liver and are also present in human kidney, the sulfoxidation reaction may also
      be expected to occur in humans exposed to HCBD.

PMID- 8555408
TI  - Alkylation of Escherichia coli thioredoxin by S-(2-chloroethyl)glutathione and
      identification of the adduct on the active site cysteine-32 by mass spectrometry.
AB  - Alkylation of reduced Escherichia coli thioredoxin by the episulfonium ion
      derived from S-(2-chloroethyl)glutathione (CEG) at physiologic pH resulted in at
      least three different alkylation products. These adducts were separated by
      reverse phase chromatography, digested with trypsin, and peptide-mapped. The
      peptide containing the active site cysteines was collected and sequenced by
      tandem mass spectrometry. Results indicate that the site of alkylation was at Cys
      32 exclusively with no alkylation at Cys-35. Raising the pH above the pKa of Cys
      35 to ionize the thiol before reacting with the episulfonium ion of CEG did not
      lead to alkylation at Cys-35, suggesting that a steric factor prevents the
      alkylating moiety of CEG from accessing this cysteine. A tryptic digest of a
      minor bis-adduct yielded an alkylated peptide which contained tyrosine, an amino
      acid known to be alkylated at its hydroxyl group by CEG. Sequencing by tandem
      mass spectrometry, however, was unsuccessful due to fragmentation of the
      alkylating moiety from the peptide. Results of this study confirm that the
      episulfonium ion of CEG can adduct thioredoxin at the active site and may have
      important toxicologic significance regarding the mechanism of 1,2-dichloroethane
      toxicity.

PMID- 8555409
TI  - Effects of some chelating agents on urinary copper excretion by the rat.
AB  - In order to estimate the potential advantages of new chelating agents which can
      enhance copper excretion in the chronic copper intoxication arising in Wilson's
      disease, the relative ability of none chelating agents to induce the urinary
      excretion of copper was compared with that of D-penicillamine (DPA) and
      triethylenetetramine.2HCl (TRIEN), all given ip at 1 mmol/kg to male Sprague
      Dawley rats. The compounds examined were as follows: tris(2-aminoethyl)
      amine.3HCl (TREN), tetraethylenepentamine.5HCl (TETREN),
      pentaethylenehexamine.6HCl (PENTEN), 1,4,7,11-tetraazaundecane.4HCl (TAUD),
      1,5,8,12-tetraazadodecane.4HCl (TADD), 1-N-benzyltriethylenetetramine.4HCl
      (BzTT), 4,7,10,13-tetraazatridecanoic acid.2H2SO4 (TTPA), 1,10-bis(2
      pyridylmethyl)-1,4,7,10-tetraazadecane.4HCl (BPTETA), and N,N-bis(2
      pyridylmethyl)-4-(aminomethyl)benzoic acid (4ABA). Of these, BzTT, TTPA, and 4ABA
      are new chelating agents not previously reported. The factors by which these
      chelating agents enhanced copper excretion over control (untreated) levels were
      as follows: DPA, 7.2; TREN, 1.6; TRIEN, 4.0; TETREN, 10.1; PENTEN, 7.8; TAUD,
      7.8; TADD, 2.6; TTPA, 5.6; BzTT, 1.8; and 4ABA, 5.5. The results indicate that it
      may well be possible to develop additional chelating agents which are equal or
      superior to those now used in the treatment of Wilson's disease, as well as
      structural types whose immunological properties may be significantly different
      from DPA or TRIEN, the compounds currently used in the clinic for this disorder.

PMID- 8555410
TI  - Differences in the tumorigenic activity of a pure hydrocarbon and a complex
      mixture following ingestion: benzo[a]pyrene vs manufactured gas plant residue.
AB  - The tumorigenic activity of manufactured gas plant residue (MGP) was evaluated in
      female A/J mice using a F0927 basal gel diet system. Adulterated diets containing
      MGP (0.10% or 0.25%) or benzo[a]pyrene (B[alpha]P; 16 or 98 ppm) were fed for 260
      days. A negative control group was maintained on a nonadulterated basal gel diet.
      Mice dosed with a single ip injection of 1.79 mg of B[a]P in a tricaprylin
      vehicle and maintained on a NIH-07 pellet diet were positive controls. In
      addition, a nontreated group of mice and a group dosed with vehicle only were
      maintained on a NIH-07 pellet diet and used as negative controls. Animal body
      weight and consumption of MGP and B[a]P were monitored throughout the study.
      Ingestion of a 0.10 or 0.25% MGP adulterated diet resulted in 70 and 100% of the
      mice developing lung tumors with a multiplicity of 1.19 and 12.17 tumors/mouse,
      respectively. Mice maintained on a 0.10% MGP diet consumed 0.7 g of MGP
      containing 1.8 mg of B[a]P while those fed a 0.25% MGP diet ingested 1.5 g of MGP
      containing 4.2 mg of B[a]P. The incidence of lung tumors in mice fed only B[a]P
      was considerably lower than that observed for animals fed a MGP diet. A diet
      containing 98 ppm B[a]P produced a significant incidence of tumor-bearing mice
      with 52% developing lung tumors. The multiplicity observed in these animals,
      however, was not significant at 0.59 tumors/mouse. A diet containing 16 ppm B[a]P
      did not produce a significant tumorigenic response in lung. Animals fed a 16 or
      98 ppm B[a]P diet consumed a total of 11 and 67 mg of B[a]P, respectively. A
      single ip dose of B[alpha]P (1.79 mg in 0.25 mL of tricaprylin) resulted in 100%
      lung tumorigenesis with a multiplicity of 15.79 tumors/mouse. In contrast to
      observed induction of lung tumors, no forestomach tumors were detected in any
      animal fed a 0.10 or 0.25% MGP adulterated diet. However, ingestion of a diet
      containing only 16 or 98 ppm of B[a]P resulted in 20 and 100% of the mice
      developing forestomach tumors, respectively. The multiplicity for forestomach
      tumors was 0.24 and 4.22 tumors/mouse, respectively. The incidence of forestomach
      carcinomas in tumor bearing mice was 8 and 52%, respectively. The ip
      administration of 1.79 mg of B[a]P resulted in an 83% forestomach tumor incidence
      having a multiplicity of 1.83 tumors/mouse. Forestomach carcinomas were induced
      in 34% of the mice exhibiting forestomach tumors. These data indicate that
      chronic ingestion of MGP- or B[a]P-adulterated diets produces significant
      differences in the tumorigenic response of female A/J mouse forestomach and lung
      tissues.

PMID- 8555411
TI  - Covalent binding of polycyclic aromatic hydrocarbon components of manufactured
      gas plant residue to mouse lung and forestomach DNA.
AB  - The present study characterized the DNA adducts induced by manufactured gas plant
      residue (MGP) and benzo[alpha]pyrene (B[alpha]P) in mouse lung and forestomach.
      The dose levels used in the present study were comparable to the levels used in a
      previous animal bioassay. Adduct formation was evaluated in female A/J mice (7
      weeks old) fed MGP (0.25%) or B[alpha]P (16 and 98 ppm) for 14 days. In addition,
      adduct formation was also evaluated in mice 24 h after the ip administration of
      1.8 mg of B[alpha]P in 0.5 mL of tricaprylin. 32P-Postlabeling combined with
      multidimensional TLC and reverse phase HPLC was used to evaluate hydrocarbon-DNA
      adducts. HPLC separation of chemical-DNA adducts formed in lung following MGP
      ingestion resulted in three distinct peaks of radioactivity eluting at 22, 32.4,
      and 33.5 min. These peaks accounted for 13, 10, and 41% of the total adducts
      detected. The adducts isolated from forestomach eluted as a series of minor peaks
      with two more distinct peaks of radioactivity at 32.4 and 33.5 min. These peaks
      accounted for 47 and 32% of the total adducts detected in forestomach,
      respectively. Ingestion of B[alpha]P (16 or 98 ppm) and the ip administration of
      B[alpha]P resulted in a single major adduct with a retention time of 32.4 min.
      The DNA adducts formed from MGP administration were further characterized by
      comparison with adducts formed following the administration of individual
      hydrocarbons and a mixture of hydrocarbons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8555412
TI  - Ovarian toxicity of 4-vinylcyclohexene and related olefins in B6C3F1 mice: role
      of diepoxides.
AB  - 4-Vinylcyclohexene (VCH) is an ovarian toxicant in mice. Studies have established
      that bioactivation of VCH to epoxides is required for its ovotoxicity, with
      vinylcyclohexene diepoxide being the most potent epoxide of VCH in terms of
      follicular depletion. To determine the role of the diepoxide in the ovarian
      toxicity of VCH and related compounds, a structure-activity study was conducted.
      Following administration (ip) of VCH for 30 days, a significant depletion of
      ovarian follicles was observed. No alteration of small ovarian follicle counts
      occurred following treatment with structural analogues of VCH (vinylcyclohexane,
      ethylcyclohexene, and cyclohexene) that contain only a single unsaturated site.
      These VCH analogues were converted to monoepoxides both in vitro and in vivo. In
      addition, when the monoepoxide forms of the VCH analogues were administered to
      mice, they were not ovotoxic. These results indicate that vinylcyclohexene
      diepoxide may be the ultimate ovotoxic metabolite of VCH. A diepoxide was also
      shown to be critical for butadiene- and isoprene-induced follicular loss.
      Butadiene monoepoxide, butadiene diepoxide, and isoprene were ovotoxic. In
      contrast, the monoepoxide, epoxybutane, was not ovotoxic. The ovotoxicity of
      these compounds correlated with their chemical reactivity as assessed by
      alkylation of nicotinamide. Vinylcyclohexene diepoxide and butadiene diepoxide
      had a 3.5- to 10-fold higher chemical reactivity as compared to their monoepoxide
      precursors and structurally related monoepoxides. Thus, a relationship exists
      between chemical reactivity and ovotoxicity. Only those compounds which are
      metabolized to a diepoxide or are a diepoxide were ovotoxic. The formation of
      these diepoxide metabolites may in turn be linked to the ovarian toxicity and
      carcinogenicity of these olefins.

PMID- 8555414
TI  - Glutathione conjugation of the cytostatic drug ifosfamide and the role of human
      glutathione S-transferases.
AB  - Development of drug resistance against alkylating cytostatic drugs has been
      associated with higher intracellular concentrations of glutathione (GSH) and
      increased expression of glutathione S-transferase (GST) enzymes. Therefore,
      enhanced detoxification by the glutathione/glutathione S-transferase pathway has
      been proposed as a major factor in the development of drug resistance toward
      alkylating agents. In this paper we describe 31P NMR and HPLC studies on the
      spontaneous and glutathione S-transferase catalyzed formation of glutathionyl
      conjugates of two metabolites of ifosfamide, i.e., 4-hydroxyifosfamide and
      ifosfamide mustard. At 25 degrees C activated ifosfamide (= 4-hydroxyifosfamide +
      aldoifosfamide) disappeared faster in the presence of a 10-fold excess of GSH
      (t1/2 = 107 min) compared to incubations without GSH (t1/2 = 266 min). No
      evidence for the formation of 4-glutathionyl ifosfamide was found. The ultimate
      alkylating species of ifosfamide is ifosfamide mustard (IM). In the absence of
      glutathione, the rate constant for the disappearance of the ifosfamide mustard
      signal at 25 degrees C (pH 7) was 1.98 x 10(-3) min-1 (t1/2 = 350 min). In the
      presence of a 10-fold molar excess of glutathione, this rate constant was 1.95 x
      10(-3) min-1 (t1/2 = 355 min), indicating that the spontaneous formation of an
      aziridinium ion is the rate-limiting event in the reaction with glutathione. The
      aziridinium ion formed from IM can deprotonate upon formation, leading to the
      formation of a (noncharged) aziridine species. This intermediate (N-(2
      chloroethyl)-N'-phosphoric acid diamide) was characterized by 31P, 1H, and 13C
      NMR spectra. When 2 mM ifosfamide mustard was incubated with 1 mM GSH in the
      presence of 40 microM GST P1-1, the formation of monoglutathionyl ifosfamide
      mustard was 2.3-fold increased above the spontaneous level. The other major human
      isoenzymes tested (A1-1, A2-2, and M1a-1a) did not influence the formation of
      monoglutathionyl ifosfamide mustard. The results of these studies demonstrate
      that increased levels of GST P1-1 can contribute to an enhanced detoxification of
      ifosfamide.

PMID- 8555413
TI  - Stereoselectivity of activation of 7,12-dimethylbenz[a]anthracene- 3,4
      dihydrodiol to the anti-diol epoxide metabolite in a human mammary carcinoma MCF
      7 cell-mediated V79 cell mutation assay.
AB  - 7,12-Dimethylbenz[a]anthracene (DMBA), one of the most carcinogenic polycyclic
      aromatic hydrocarbons in rodent bioassays, is metabolically activated in many
      tissues to "bay-region" DMBA-3,4-diol-1,2-epoxides (DMBADE). Unlike
      benzo[a]pyrene, for which the high biological activity of the (7R,8S)-diol
      (9S,10R)-epoxide has been established, the low chemical stability of anti-DMBADE
      has made it impossible to evaluate the role of specific stereoisomers in the
      biological activity of DMBA. In order to characterize the role of formation of
      DMBADE diastereomers in the induction of mutations, postlabeling assays using
      [35S]phosphorothioate with adduct separation by HPLC and immobilized boronate
      chromatography analyses were developed to allow separation and quantitation of
      DNA adducts formed from each stereoisomer of DMBADE. In DMBA-treated hamster
      embryo cell cultures, large quantities of three major adducts (anti-DMBADE
      deoxyguanosine, anti-DMBADE-deoxyadenosine, and syn-DMBADE-deoxyadenosine) along
      with five minor adducts were completely resolved and quantitated. The DNA
      isolated from a human mammary carcinoma MCF-7 cell-mediated V79 cell mutation
      assay treated with increasing doses of racemic DMBA-3,4-dihydrodiol contained
      large amounts of two anti-DMBADE-DNA adducts. The anti-DMBADE adducts accounted
      for more than 90% of the total adducts at all doses. The number of 6-thioguanine
      resistant mutants was proportional to the amount of anti-DMBADE-DNA
      adducts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8555416
TI  - Slow conformational exchange in DNA minihairpin loops: a conformational study of
      the circular dumbbell d<pCGC-TT-GCG-TT>.
AB  - In recent years various examples of highly stable two-residue hairpin loops
      (miniloops) in DNA have been encountered. As the detailed structure and stability
      of miniloops appear to be determined not only by the nature and sequence of the
      two bases in the loop, but also by the closing base pair, it is desirable to
      carry out in-depth studies of especially designed small model DNA compounds.
      Therefore, a circular DNA dumbbell-like molecule is tailored to consist of a stem
      of three Watson-Crick base pairs, flanked on each side by a minihairpin loop. The
      resulting circular DNA decamer 5'-d<pCGC-TT-GCG-TT>-3' (I) is studied in solution
      by means of nmr spectroscopy. At a temperature of 269 K the molecule occurs in a
      50/50 mixture of two dumbbell structures (denoted L2L2 and L2L4). L2L2 contains
      three Watson-Crick C-G base pairs and two two-residue loops (H2-family type) in
      opposite parts of the molecule. On raising the temperature from 269 to 314 K, the
      L2L4 conformer becomes increasingly dominant (95% at 314 K). This conformer has a
      partially disrupted closing G-C base pair in the 5'-GTTC-3' loop with only one
      remaining solvent-accessible hydrogen bond between NH alpha of the cytosine C(1)
      and O6 of the guanine G(8), whereas the opposite 5'-CTTG-3' loop remains stable.
      The disruption of the C(1)-G(8) base pair in the L2L4 form is correlated with the
      presence of a syn orientation for the C(1) base at the 5'-3' loop-stem junction
      in the 5'-GTTC-3' loop. The two conformers, L2L2 and L2L4, occur in slow
      equilibrium (2-20 s-1). Moderate line broadening of specific 1H, 13C, and 31P
      resonances of residues C(1), G(8), T(9), and T(10) at low temperatures, due to
      chemical exchange between L2L2 and L2L4, show that the interconversion from an
      anti to syn conformer in residue C(1) has a small local effect on the structure
      of the dumbbell. T1 relaxation measurements, chemical-shift considerations, and
      complete band-shape calculations of the exchange process of the G(8) imino proton
      reveal a possibility for the existence of multiconformational states in the anti
      syn equilibrium.

PMID- 8555415
TI  - Species-dependent differences in biotransformation pathways of 2-methylpropene
      (isobutene).
AB  - The biotransformation of 2-methylpropene, a gaseous alkene widely used in
      industry, was investigated in vitro in liver tissue of rats, mice, and humans.
      Interspecies comparison revealed that the lowest levels of the primary epoxide
      metabolite were detected in incubations of 2-methylpropene with human liver
      homogenate, followed by rat and mouse, respectively. Among the human liver
      samples, however, important interindividual variations were observed. Out of the
      16 samples analyzed, only 2 contained measurable epoxide amounts, while in the
      other samples only traces were detectable. The involvement of rat liver
      cytochrome P450 2E1 in the activation of 2-methylpropene to its epoxide 2-methyl
      1,2-epoxypropane has been established. The lower capacity of the mixed function
      oxidase system in human liver samples compared to rodents is confirmed.
      Concerning epoxide detoxifying enzymes, a high microsomal epoxide hydrolase
      activity was observed in human liver tissue and an intermediate in rat liver,
      while a low activity was measured in mouse liver. These findings were inversely
      correlated with the epoxide levels measured in vitro in liver tissue of the three
      species studied. It can be concluded that, as far as the in vitro metabolism of 2
      methylpropene is concerned, neither mouse nor rat represents a good model for the
      human situation. Although, the same biotransformation pathways are involved,
      marked quantitative differences in epoxide levels were observed. The results
      indicate that human liver tissue is exposed in vitro to smaller concentrations of
      the primary metabolite 2-methyl-1,2-epoxypropane than rodent liver.

PMID- 8555417
TI  - Properties of Auricularia auricula-judae beta-D-glucan in dilute solution.
AB  - A water-soluble glucan A was isolated from the fruit body of Auricularia auricula
      judae. It is composed of a backbone chain of beta-(1-->3)-linked D-glucose
      residues, two out of three glucose residues being substituted at C-6 positions
      with a single glucose unit. The weight average molecular weight Mw, number
      average molecular weight Mn, and intrinsic viscosity [eta] of the fractionated
      samples were studied at 25 degrees C in water and in dimethylsulfoxide (DMSO).
      The Mark-Houwink equation was established as [eta] = 6.10 x 10(-4) Mw1.14 for the
      glucan A having Mw ranging from 9 x 10(5) to 1.6 x 10(6) in water. The values of
      [eta] in water are far higher than those in DMSO, but the values of Mn measured
      in water are the same as those in DMSO. Analysis of Mw and [eta] in terms of the
      known theories for rods and wormlike chains yielded 1030 +/- 100 nm-1, 90 +/- 20
      nm, 1.3 +/- 0.3 nm, and 0.26 +/- 0.03 nm for molar mass per unit contour length
      ML, persistence length q, diameter d, and contour length h per main-chain glucose
      residue, respectively. The present data suggest that glucan A dissolves in water
      as single-stranded helical chains and in DMSO as semiflexible chains.

PMID- 8555418
TI  - Thermodynamics of melting of the circular dumbbell d<pCGC-TT-GCG-TT>.
AB  - The conformational behavior of DNA minihairpin loops is sensitive to the
      directionality of the base pair that closes the loop. Especially tailored
      circular dumbbells, consisting of a stem of three Watson-Crick base pairs capped
      on each side with a minihairpin loop, serve as excellent model compounds by means
      of which deeper insight is gained into the relative stability and melting
      properties of hairpin loops that differ only in directionality of the closing
      pair: C-G vs G-C. For this reason the thermodynamic properties of the circular
      DNA decamers 5'-d<pCGC-TT-GCG-TT>-3' (I) and reference compounds 5'-d<pGGC-TT-GCC
      TT>-3' (II) and 5'-d(GCG-TC-CGC)-3' (III) are studied by means of nmr
      spectroscopy. Molecules I and II adopt dumbbell structures closed on both sides
      by a two-membered hairpin loop. At low temperature I consists of a mixture of two
      slowly exchanging forms, denoted L2L2 and L2L4. The low-temperature L2L2 form is
      the fully intact minihairpin structure with three Watson-Crick C-G base pairs.
      The high-temperature form, L2L4, contains a partially disrupted closing G-C base
      pair in the 5'-GTTC-3' loop, with the cytosine base placed in a syn orientation.
      The opposite 5'-CTTG-3' loop remains stable. A study of the noncircular hairpin
      structure III shows similar conformational behavior for the 5'-GTTC-3' loop as
      found in I; a syn orientation for C(6) and two slowly exchanging imino proton
      signals for G(3). The melting point Tm of II was estimated to lie above 365 K.
      The Tm value of the duplex stem and the 5'-CTTG-3' loop of the L2L4 form of I is
      352 +/- 2 K. The delta H0 is calculated as -89 +/- 10 kJ/mol. The Tm value
      determined for the individual residues of the 5'-GTTC-3' loop lies 4 degrees-11
      degrees lower. The enthalpy delta H0 of melting the thymine residues in the 5'
      GTTC-3' loop is calculated to be -61 +/- 7 kJ/mol. Thermodynamic data of the
      equilibrium between the slowly exchanging two- and four-membered loop conformers
      of I reveal an upper limit for delta H0 of +30 kJ/mol in going from a two
      membered to a four-membered loop, in agreement with the enthalpy difference of
      +28 kJ/mol between the two loops at the Tm midpoint. For hairpin III the upper
      limit for delta H0 in going from a two-membered to a four-membered loop amounts
      to +/- 21 kJ/mol.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8555419
TI  - Incorporation of diacids into the polyglycine II structure: model studies.
AB  - Aliphatic diacids are often incorporated into polypeptide structures in order to
      obtain model compounds for hormones, protein turns, etc. They are also
      fundamental components of many commercial polyamides. On the other hand glycine,
      the simplest amino acid, shows unique conformational features. In order to better
      understand the structure of such compounds, we have synthetized and determined
      the molecular structure of three models represented by the general formula CH3
      CH2-CH2-NH-CO-CH2-NH-CO-(CH2)n-2-CO-NH-CH2-CO-NH-CH2-CH2-CH3, with n = 3, 4, or
      6. Conformational differences have been found in the dicarboxylic moiety, whereas
      glycine always has the polyglycine II conformation. The -CO-(CH2)n-2-CO-segment
      adopts a folded conformation: SS, TGT, and SGTGS for n = 3, 4, and 6,
      respectively. Molecular packing is always pseudohexagonal and a network of
      hydrogen bonds oriented in three directions at 120 degrees is formed. The results
      are of interest in order to provide information about polyamides in which glycine
      residues are incorporated. Our results confirm the tendency of glycine residues
      to adopt the polyglycine II conformation in its copolymers with aliphatic
      compounds.

PMID- 8555420
TI  - Anomalous temperature fluorescence quenching of N-Trp terminal peptides.
AB  - The photophysics of Trp-containing peptides is extremely affected by the position
      of the indole ring with respect to substituents. In this work an unusual
      temperature fluorescence quenching behavior is presented. The N-tryptophan
      terminal peptides (N-Trp) show an increase of the static emission intensity as
      rising the temperature from 10 to about 40 degrees C. the anomaly is typical of
      the N-Trp terminal peptides since neither tryptophan (Trp) nor glycyl-tryptophan
      (Gly-Trp) and alanyl-tryptophan (Ala-Trp) show the same trend; a similar behavior
      is not detected in the C-tryptophan terminals. The other important features are
      the wavelength and pH dependence of the effect. The anomaly is in fact detected
      only at neutral pH and for excitation wavelength near the red edge of the UVB
      absorption band of indole. An interpretation of the anomaly is suggested, though
      more sophisticated techniques are needed to better focus the problem; the model
      proposed involves the superimposition of a ground state effect (the temperature
      induced equilibrium shift from the zwitterionic to the anionic form of the
      peptides) and an excited state mechanism. At present no unique interpretation can
      be provided about the excited state mechanism that favors the anomaly ans some
      suggestions are discussed.

PMID- 8555421
TI  - Influence of sample pH on the conformational backbone dynamics of a
      pseudotripeptide (H-Tyr-Tic psi [CH2-NH]Phe-OH) incorporating a reduced peptide
      bond: an NMR investigation.
AB  - In the present paper we investigate the influence of sample pH on the
      conformational and dynamical properties of the pseudotripeptide H-Tyr-Tic psi
      [CH2-NH]Phe-OH (TIP[psi]; Tic: 1,2,3,4,-tetrahydroisoquinoline-3-carboxylic acid)
      using various one- and two-dimensional nmr techniques in conjunction with
      molecular modeling. Studies were conducted at three different pH levels
      corresponding to the zwitterionic peptide containing a formal positive charge (pH
      3.1), the deprotonated molecule (pH 9.1), and a situation at neutral pH (pH 7.2)
      involving both protonated and deprotonated states of the reduced peptide bond.
      Analysis of the one-dimensional1H-nmr spectra reveals that in solution TIP[psi]
      is in slow dynamic exchange between conformations containing cis and trans
      configurations of the Tyr-Tic bond. An nmr pH dependence study of the cis:trans
      ratio indicated that the exchange process was governed by the protonation state
      of the reduced bone amine. From the nmr data, reduced peptide bond pK alpha
      values of 6.5 and 7.5 were determined for the cis and trans conformers,
      respectively. It was concluded that conformations containing a trans Tyr-Tic bond
      are stabilized at low pH by an intramolecular hydrogen bond between the Tyr
      carbonyl and the reduced peptide bond protonated amine. This observation was
      corroborated by molecular mechanics investigations that revealed low energy trans
      structures compatible with nmr structural data, and furthermore, were
      consistently characterized by the existence of a strong N+ H ... O = C
      interaction closing a seven-membered cycle. The dynamics of cis-trans
      isomerization about the Tyr-Tic peptide bond were probed by nmr exchange
      experiments. The selective presaturation of exchanging resonances carried out at
      several temperatures between 50 and 70 degrees C allowed the determination of
      isomerization rate constants as well as thermodynamic activation parameters.
      delta G not equal to values were in close agreement with the cis-->trans energy
      barrier found in X-Pro peptide fragments (approximately 83 kJ/mol). A large
      entropic barrier determined for the trans-->cis conversion of TIP[psi] (5.7 JK-1
      mol-1 at pH 3.1;6.5 J K-1 mol-1 at pH 9.1) is discussed in terms of decreased
      solvent molecular ordering around the conformers possessing a trans Tyr-Tic bond.
      Evidence that the neutral form of the reduced peptide bond gains rigidity upon
      protonation was obtained from relaxation measurements in the rotating frame. T1
      rho measurements of several protons in the vicinity of the reduced peptide bond
      were made as a function of spin-lock field.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8555422
TI  - 1H-nmr studies on the structure of a new thionin from barley endosperm.
AB  - A new thionin from barley, omega-hordothionin, has been shown to exist in aqueous
      solution as a mixture of two different isoforms in a 3:2 ratio, as revealed by a
      complete analysis of its two-dimensional 1H-nmr spectra. The conformational
      heterogeneity arises from cis-trans isomerism about the Phe 12-Pro 13 peptide
      bond, where the major form corresponds to the cis conformation. The complete
      assignment of chemical shifts and nuclear Overhauser effects (NOEs) of the two
      isoforms allows a detailed comparative analysis of their conformational
      properties, even though a complete calculation of their solution structures is
      not possible because of a somewhat limited number of NOE constraints. Structures
      for the two isomers could be modeled, however, on the basis of the high
      structural homology between omega-hordothionin and related gamma-thionins, and
      under the conditions of satisfying all observed experimental data. The two
      isoforms adopt practically identical global folds and the structural changes
      imposed by cis-trans isomerization are confined to the region proximal to Pro 13.
      The cis-trans isomerism occurs in a conserved loop connecting the first beta
      strand of the triple-stranded antiparallel beta-sheet and the alpha-helix. A
      comparative analysis of the sequences of this loop in the different thionins
      suggests that the cis-trans equilibrium about the X-Pro peptide bond depends on
      the size of the side chain of X (X = Gly in gamma-thionins and Phe in omega
      thionin). The structural homology of this new thionin with gamma-thionins as well
      as with some scorpion toxins and insect defensins suggests that these proteins
      may share a common mode of functional activity.

PMID- 8555423
TI  - Interaction of mastoparan-B from venom of a hornet in Taiwan with phospholipid
      bilayers and its antimicrobial activity.
AB  - Mastoparan B (MP-B), an amphiphilic alpha-helical peptide newly isolated from the
      hornet Vespa basalis, was studied in comparison with mastoparan (MP), in terms of
      interaction with the phospholipid bilayer and of hemolytic and antimicrobial
      activity. The amphiphilic structure of MP-B has more hydrophilic amino acid
      residues in the hydrophilic surface than that of MP. Although each peptide had a
      considerably different effect on the interaction with lipid bilayers (e.g., their
      conformation in the presence of acidic and of neutral lipids and dye-release
      ability from the encapsulated liposomes), on the whole the interaction mode was
      similar. MP-B caused a change in the shape of erythrocytes from normal discoid to
      a crenated form (named echinocytes). MP exhibited strong activity against gram
      positive bacteria but not against gram-negative ones. Contrary to this, MP-B
      showed both strong activity against gram-positive bacteria and potent activity
      against gram-negative bacteria. Whereas both peptides have almost the same
      residues on the hydrophobic side, the difference in the hydrophilic surface area
      on the molecules seems to lead to the subtle change in its interaction with
      membranes, resulting in the alteration of biological activity.

PMID- 8555424
TI  - Dielectric study of the cooperative order-disorder transition in aqueous
      solutions of schizophyllan, a triple-helical polysaccharide.
AB  - Schizophyllan exists in aqueous solution as a triple helix, which is intact at
      room temperature. Its aqueous solution forms some ordered structure at low
      temperatures but undergoes a sharp transition to a disordered structure as the
      temperature is raised. The transition temperature Tc is about 7 and 18 degrees C
      for H2O and D2O solutions, respectively. This transition was followed by time
      domain reflectometry to investigate dynamic aspects of the transition. In
      addition to a major peak around 10 GHz, the dielectric dispersion curve of a 20
      wt % schizophyllan in D2O exhibited a small peak around 100 MHz below Tc and
      around 10 MHz above Tc. The major peak is due to bulk water, whereas the 100 MHz
      peak is assigned to "bound" or "structured" water, and that around 10 MHz to side
      chain glucose residues. However, unlike usual bound water reported for biopolymer
      solutions, this "structured" water disappears abruptly when the temperature
      becomes close to Tc without accompanying a conformational transition of the main
      chain. The above assignment is consistent with the structure of the ordered phase
      derived from previous static data that it consists of side-chain glucose residues
      along with nearby water molecules surrounding the helix core that are interacting
      with each other loosely through hydrogen bonds, and spreads radially only a layer
      of one or two water molecules but a long distance along the helix axis.

PMID- 8555425
TI  - The week in phylogeny and ontogeny: opportunities for oncology.
AB  - Like circadian systems, multiseptans are apparently frequent if not ubiquitous
      chronome components. There is growing evidence from both basic and applied
      viewpoints that built-in circaseptans play a role complementary to the circadian
      system as does the circasemiseptan component. We have here compared circaseptans
      and circasemiseptans, by reference to their corresponding circadians, in humans
      (at early stages of development or as adults in society vs. isolation in caves)
      and across species (notably in organisms identified as early inhabitants of the
      earth), in growth and regeneration, and in tumor markers, presumably reflecting
      the host carrying a malignant growth, in pre-disease and in overt illness.
      Intermodulations within the components of chronomes of a given set of variables,
      and among components of chronomes of different variables, the feedsidewards, are
      the basic characteristics of life. Many frequencies lower than those here
      considered, including the biologic year and a component corresponding to the
      length of the solar cycle have been opportunistically studied. Because of
      practicality only, the relation of circasemiseptan and circaseptan chronome
      components to circadian components was here explored as a hint that much
      information lies in the relations among rhythms with different frequencies, for
      oncologists in particular.

PMID- 8555426
TI  - Studies on circadian periodicity of plasma 17-hydroxycorticosteroids (17-OHCS) in
      carcinoma of the breast.
AB  - Circadian periodicity of plasma 17-hydroxycorticosteroids (17-OHCS) was studied
      in 25 histopathologically proved breast cancer patients pre operatively and on
      the 9th postoperative day and in 15 healthy women under tropical conditions. A
      marked rhythm in plasma 17-OHCS concentration was noticed in healthy controls.
      The maximal concentration occurred at 06:00 followed by a consistent decline
      throughout the daytime, reaching a minimum at 00:00 with an amplitude
      statistically significantly different from zero and an acrophase around 08:56.
      The plasma 17-OHCS concentration was found to be elevated at all sampling hours
      in breast cancer patients, irrespective of the stage of the disease. However, the
      degree of elevation and disruption of rhythm was more pronounced in advanced
      sages, preoperatively, in comparison to other groups. Moreover, the values
      declined markedly at all collection hours after mastectomy, approaching usual
      values and rhythm characteristics on the 9th postoperative day.

PMID- 8555427
TI  - Marker rhythms for cancer chronotherapy. From laboratory animals to human beings.
AB  - The author reviews basic knowledge related to circadian rhythmicities potentially
      harmful for cancer chronotherapy scheduling in laboratory rodents and in human
      beings. Circadian rhythms have been evidenced both in animals and in humans, in
      metabolically active or actively dividing healthy tissues, as well as in most
      experimental tumors and in some human cancers. These phenomena, taken together
      with the chronopharmacology of anticancer drugs, can account for the diurnal
      variability of tolerance and of antitumor activity of oncolytic drugs. Of
      interest in clinical practice, recently large clinical trials have confirmed the
      achievement of an improvement in clinical outcome from overall delivered higher
      doses of chemotherapy allowed by the chronotolerance concept. The possibility of
      proposing individualized chronotherapy schedules from precise gauging (even in
      saliva or in urine) of cortisol and various human tumor markers is also
      discussed.

PMID- 8555428
TI  - Immunotoxicologic effects of ethylene dibromide in the mouse and their modulation
      by the estrous cycle.
AB  - Estrous cycle modulation of immunologic sensitivity to ethylene dibromide (EDB)
      was studied in addition to toxicologic end points. Female B6C3F1 mice were
      injected intragastrically with 31.25, 62.5, or 125 mg/kg EDB for 5 days a week
      for 12 weeks. Vaginal smears determined the estrous cycle. At 125 mg/kg there
      were decreases in hemoglobin and hematocrit and longer estrous cycles (5.5 vs 4.3
      days, p = 0.006), and increases in cholesterol, triglycerides, total protein, and
      albumin. The negative dose response seen for T- and B-cell mitogenesis around
      metestrus was absent for mice near estrus. The high dose of EDB prolonged
      intervals between estrus, was immunotoxic and immunosuppressive.

PMID- 8555429
TI  - Rationales to consider the use of melatonin as a chrono-oncotherapeutic drug.

PMID- 8555430
TI  - Cancer marker assessment: case report on salivary and urinary CEA.
AB  - A circadian rhythm is demonstrated for salivary CEA in a clinically healthy man
      who collected unstimulated saliva samples around the clock for 4 days. Its
      acrophase occurs around 07:00, slightly later than for patients with colon
      cancer. A circadian rhythm of borderline statistical significance is found for
      the urinary excretion rate of CEA determined during the same span by this
      patient. It has an acrophase occurring around 15:00, differing from that of
      salivary CEA. Although CEA may have only limited value to assess tumor burden,
      even when determined in blood, rhythm characteristics of tumor markers such as
      CEA await applications for guiding treatment timing and for detecting earliest
      chronome alterations not only in the case of an overt cancer but as a feature of
      predisease and/or disease risk elevation.

PMID- 8555431
TI  - Toward a chronome of superfused pike pineals: about-weekly (circaseptan)
      modulation of circadian melatonin release.
AB  - In continuous darkness for about 5.5 days in eleven replications, the pineal
      shows neither only a decreasing trend nor only a damped circadian rhythm; there
      is an infradian modulation: after an initial decline, melatonin production
      increases again, with a pattern compatible with the assumption, for at least one
      cycle, that a built-in pineal "week" has a larger extent of predictable change
      than that of a pineal "day". Melatonin release from the isolated pike pineal
      reveals a circadian rhythm which, on the average, is damped, but demonstrable in
      the second half of a time series covering 5.5 days (P < 0.05). At fixed
      environmental temperatures of 10, 15, 19 or 20 degrees C (the latter two pooled),
      single and population mean cosinor analyses reject the assumptions of zero
      circaseptan and circadian amplitudes in the chronome of the pineal from the pike
      (Esox lucius L.). The circaseptan pattern is confounded by possible trends. The
      time series analyzed are brief, yet validate, by a one-way analysis of variance
      in plexograms as well as by cosinor, an about-weekly pattern, if not (yet)
      rhythm, on the basis of 745 determinations. The circaseptan- and circasemiseptan
      to-circadian amplitude ratios are numerically larger than unity, on the average
      (2.014; 95% confidence interval, CI: 1.120 to 3.641 and 1.107; CI: 0.724 to
      1.693, respectively). A positive correlation of the urinary excretion rate of a
      major breakdown product of melatonin of a cancer patient with a circulating
      cancer marker serving as a gauge of disease progression lends an oncologic
      perspective to the amplitude ratios of melatonin release in vitro here
      reported.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8555432
TI  - Circadian characteristics of interleukin-6 in blood and urine of clinically
      healthy men.
AB  - The cytokine interleukin-6 (IL-6) is a multi-functional small peptide molecule
      that is produced by various types of lymphoid and non-lymphoid cells and plays a
      central role in hematopoiesis, host defense mechanisms, and acute phase
      reactions, including regulation of inflammatory and immune responses. A high
      sensitivity ELISA assay was applied to serum (S) and urine (U) samples available
      from 10 men (median age = 50y, range = 46-71y) in order to compare circadian
      characteristics of IL-6 between assays and in 2 biological fluids. S and U
      samples were collected at 3-h intervals for 24hrs beginning at 19:00h on May 14,
      1993 (8 samples/subj) and frozen at -25 degrees C until analysis. IL-6 in U was
      adjusted for time & volume (pg/hr) and assigned to midpoint of collection
      interval. A significant time-effect was found by ANOVA and a high-amplitude
      circadian rhythm was detected by the least-squares fit of a 24-hr &/or 24+12-hr
      cosine for each assay. Higher serum IL-6 values were detected throughout the
      night, with a peak at 01:00h, and lower values throughout the day, with a nadir
      at 10:00h. In contrast, IL-6 values in urine were highest during the day, with a
      major peak in the afternoon at 17:30h and a minor peak at 08:30h, and lowest
      values overnight, with a nadir at 23:30h. Of interest, the rhythm in urinary IL-6
      concentration (pg/ml) was more prominent than hourly excretion rate (pg/hr).
      Thus, endogenous IL-6 (and possibly other cytokine) levels may be significantly
      influenced by their large and predictable day-night variations and the biological
      fluid used.

PMID- 8555433
TI  - Spectral differences between epitopes in the cronomes of salivary CA130 and
      CA125.
AB  - Ovarian tumor markers CA125 and CA130 are here investigated in the search for
      harbingers of an elevated cancer risk or pre-cancer. A circadian rhythm of large
      amplitude is demonstrated for salivary CA125 and CA130 of a clinically healthy 28
      year-old woman (AP). The circadian rhythms of both markers found in AP have a
      pattern similar to that of a patient (EH) with a mullerian cancer involving the
      ovary, with high values in the early morning and low values in the afternoon.
      Whereas acrophases occur approximately at the same circadian stage in both AP and
      EH, the MESOR and circadian amplitude are higher in EH as compared to AP. The
      circadian rhythm of salivary CA130 of AP is similar to that of other clinically
      healthy women. CA130 concentrations are lower than CA125 concentrations in
      unstimulated saliva (before rinsing of the mouth) in this clinically healthy
      woman (AP), and in other women studied herein. This difference between CA130 and
      CA125 concentrations is observed irrespective of circadian stage and irrespective
      of the concentration range of CA125 at the outset. After rinsing of the mouth, a
      statistically significant decrease in both CA130 and CA125 concentration is
      observed in AP and in another healty woman (GC) who collected saliva both before
      and after rinsing of the mouth.

PMID- 8555434
TI  - Metachronanalysis of circannual and circasemiannual characteristics of human
      suprachiasmatic vasopressin-containing neurons.
AB  - We here test for and detect anticipated about-yearly (circannual) changes in the
      volume and number of vasopressin-containing neurons in the human suprachiasmatic
      nucleus. We then resolve inferential statistical parameters quantifying the
      extent and timing (the amplitude and acrophase) of the circannual rhythm
      previously missed by data inspection and classical biometry. We parametrize about
      half-yearly changes previously validated by non-parametric statistical tests. New
      dynamic circannual and circasemiannual endpoints thus become available for basic
      investigation and the assessment of disease risk elevation and/or
      chronoprotopathology. It was earlier demonstrated that the circannual rhythms of
      prolactin and TSH are prominent classifiers of individuals at high versus low
      familial and other risk for developing breast or prostate cancer. Any neurocrine
      or neural mechanisms contributing to this classification are now amenable to
      study, on a population basis, with the dynamic hypothalamic rhythm
      characteristics yielded by this metachronanalysis.

PMID- 8555435
TI  - Chronobiologic aspects of urinary gonadotropin peptide (UGP).
AB  - When using urinary gonadotropin peptide (UGP) as a marker for ovarian cancer, a
      circadian rhythm of large amplitude is best assessed for improving preanalytic
      quality control, for specifying how often and when to sample and for resolving
      chronobiologic endpoints. In a patient (EH, 73 y) with an ovarian (Mullerian)
      adenocarcinoma, overall high UGP values occurred consistently around 07:00
      (standard deviation, SD = 2 h), similar to the timing observed in a presumably
      healthy woman. The circadian rhythm of EH averages in amplitude about 45% of the
      daily mean value (SD = 15%). The results indicate the desirability of deriving
      time-specified reference limits in health for an improved diagnostic value of
      UGP. The circadian UGP pattern awaits tests of applications for a chronodiagnosis
      of ovarian cancer, for optimizing treatment efficacy by timing according to
      rhythms, and conceivably for detecting earliest precancer risk.

PMID- 8555436
TI  - Physical chemistry and the biologic week in the perspective of chrono-oncology.
AB  - The computation of spectra and cross-spectra yielding coherences suggests that
      there exist certain relationships between rhythmicities and electromagnetic
      fields that are external to the biologic structure studied. Models are here
      provided which may prompt further investigation by allowing at least tentative,
      quantitative temporal insights into physico-chemical aspects of the biologic
      week. On the basis of empirical data, a computation of the oscillating frequency
      during the diffusion of ions in a magnetic field can be performed. The frequency
      of some ions found in cells (Ca2+, K+, Na+, Mg2+) and of some proteins (albumin,
      hemoglobin) can be calculated given the diffusion constant in cells, the magnetic
      field strength, the relative molecular mass and the effective charge. For a field
      of 10(-9) Tesla, the oscillating period of K+ is about 180 hours, that of Ca2+
      about 160 hours, that of Na+ about 150 hours and that of Mg2+ about 145 hours;
      the period lengths of albumin and hemogiobin are of the order of 30 and 40 days.
      Without a consideration of any receptors, the results seem to represent, at least
      numerically, realistic components in the time structure investigated by
      chronobiology.

PMID- 8555437
TI  - Chronome of urinary 6-sulfoxy-melatonin excretion, circulating CA125, cancer
      progression and therapeutic response.
AB  - The longitudinal follow-up of a patient with an advanced adenocarcinoma of the
      ovary sheds new light on the involvement of the pineal in carcinogenesis. The
      changes in the circadian MESOR of 6-sulfoxy-melatonin following a course of
      chemotherapy may differ in relation to the success or failure of treatment, yet
      the MESOR does not correlate with tumor burden assessed by circulating CA125. By
      contrast, the ratio of circaseptan-to-circadian amplitudes involving two chronome
      components correlates with the cancer marker. To that extent, the study reveals a
      critical about 7-day (circaseptan) aspect of the pineal involvement in cancer
      progression. This information could be exploited in designing schedules of
      melatonin administration to cancer patients.

PMID- 8555438
TI  - Circadian phase relationships between peripheral blood variables and bone marrow
      proliferative activity in clinical health.
AB  - Potential life-threatening drug induced side effects to the bone marrow (BM) may
      be reduced by the proper timing of chemotherapy (chronotherapy) according to
      circadian stage. Blood and BM samples were obtained concomitantly every 4h for
      24h from 16 healthy men (19 series total) to compare circadian patterns in
      peripheral blood (PB) as reference rhythms for BM DNA. Circadian rhythm
      characteristics from population mean cosinor summary follow (phi = acrophase): in
      PB: cortisol, p = 0.014, phi = 13:04h; leukocytes (/mm3), p = 0.001, phi =
      00:16h; neutrophils (%WBC), p = 0.001, phi = 15:36h; neutrophils (/mm3), p =
      0.101, phi = 22:36h; lymphocytes (%WBC), p = 0.009, phi = 03:24h; lymphocytes
      (/mm3), p = 0.001, phi = 0.1:40h; in BM:DNA, p = 0.014, phi = 13:04h; and CFU-GM,
      p = 0.041, phi = 13:12h. When all DNA synthesis (S-phase) values were correlated
      with PB values by repeatedly advancing the DNA values by 4h, significant
      correlations with cortisol were found by advancing S-phase by 8h (r = 0.19, p =
      0.050). Lymphocytes correlated best with S-phase when shifted by 12h (r = 0.37, p
      < 0.001), while neutrophils as % of leukocytes (but not absolute counts)
      correlated significantly when S-phase was delayed by 4h (r = 0.35, p < 0.001).
      These correlations confirm the phase relationships determined for the circadian
      rhythms. These findings suggest that the proper timing of an optimized anticancer
      cytotoxic chronotherapy can be confirmed and guided via sampling of marker
      rhythms (such as lymphocytes) in peripheral blood which have been found to
      demonstrate a relatively fixed relation to the circadian stage-dependent
      variation in unaffected BM proliferative activity.

PMID- 8555439
TI  - Circasemiseptan (about-half-weekly) and/or circaseptan (about-weekly) pattern in
      human mitotic activity?
AB  - This review and metachronanalysis was prompted by the presence of a
      circasemiseptan pattern (P < 0.05) found by population-mean cosinor in published
      data characterizing murine malignant growth after treatment with cyclophosphamide
      (1-4). For cancer chronotherapy (5-9), the analyses serve to suggest the
      desirability to extend the focus beyond circadian aspects of drug timing and drug
      effect to a broader view that takes into account as much of the body's make-up in
      time as is practical. Among the different components of a chronome (the time
      structure of rhythms with different frequencies and trends in a given variable),
      the 3.5-day patterns (circasemiseptans) and the 7-day patterns (circaseptans) are
      more readily accessible to measurement and thus to manipulation and optimization
      than infradians with even lower frequencies; they may also be pertinent to the
      scheduling of infusions covering several days, particularly those using drug
      administration devices, some of which are programmable. Should circaseptans and
      circasemiseptans characterize the host as well as the tumor, the drug
      administration schedule could be optimized for both treatment efficacy and host
      tolerance, with a view of infradian as well as of circadian and ultradian
      rhythms.

PMID- 8555440
TI  - X-irradiation chronosensitivity and circadian rhythmic proliferation in healthy
      and sarcoma-carrying rats' bone marrow.
AB  - Mitotic activity of bone marrow and tumor of sarcoma-bearing rats and of bone
      marrow of healthy controls is circadian periodic. Whereas the circadian rhythm in
      mitotic activity of bone marrow is similar for intact and tumor-bearing rats,
      with a peak occurring shortly after the onset of the dark (activity) span, the
      circadian rhythm in mitotic activity of tumor has a much smaller amplitude and a
      different acrophase occurring late in the dark span. This difference in acrophase
      of mitotic activity of bone marrow and tumor has important implications for
      scheduling the administration of oncotherapy. For the tumor model examined
      herein, it suggests the possibility to achieve concomitantly near maximal
      efficacy and near minimal myelotoxicity, a result awaiting further investigation
      in humans with different kinds of malignancies.

PMID- 8555441
TI  - Chronometaanalysis: circasemiseptan (3.5-day) pattern in mitotic activity of
      murine sarcoma after treatment with cyclophosphamide.
AB  - This note focuses attention upon infradians in mitotic activity of a murine
      sarcoma. Starting on day 8 after the inoculation of mice with a sarcoma, three
      different doses of cyclophosphamide, one dose at three different circadian times,
      were injected and tumor was sampled with serial independence, mostly at 12-hour
      intervals during the 4 ensuing days. A metachronanalysis of these heterogeneous
      data, collected for a different purpose with different doses and at different
      circadian times, reveals the presence of a circasemiseptan pattern (P < 0.05 by
      population-mean cosinor). Without a longitudinal replication, the result is
      described only as a pattern rather than as a (recurring) rhythm, characterizing
      malignant growth after treatment with cyclophosphamide. For cancer chronotherapy,
      the analyses serve to suggest the desirability to replace exclusive focus upon
      circadian aspects of drug timing and drug effect by a broader view that takes
      into account as much of the chronome as is practical. Among the different
      components of a chronome (i.e., the time structure of rhythms with different
      frequencies and trends in a given variable), the circasemiseptans (and circa
      septans) are more readily accessible than infradians with even lower frequencies;
      they may also be pertinent to the scheduling of infusions covering several days,
      particularly those using drug administration devices, some of which are
      programmable. Since circaseptans and circasemiseptans may characterize the host
      as well as the tumor, infradian drug administration schedules could be sought
      that optimize both treatment efficacy and host tolerance.

PMID- 8555443
TI  - Circadian rhythm of sister chromatid exchanges in human chromosomes.
AB  - Since sister chromatid exchange (SCE) relates directly to DNA synthesis which is
      circadian periodic, this study examines whether a circadian rhythm also
      characterizes SCEs. In 4-hourly blood samples collected for 48 hours on three
      diurnally active, nocturnally resting subjects with no family history of
      chromosome aberrations or instability, a circadian rhythm is demonstrable with an
      acrophase occurring around 14:45. The circadian amplitude is only of the order of
      10% of the MESOR in untreated cultures or in cultures exposed to cefodizime. It
      remains more or less unchanged in cultures exposed to mitomycin-C, while the
      MESOR increases by about a factor of 2. In studies of human chromosome
      aberrations, the circadian rhythmicity of SCE should be taken into consideration.

PMID- 8555442
TI  - Toward salivary-urinary chronosensitivity testing: chronomes of OVX1, M-CSF and
      CA130.
AB  - Several rhythmic components were previously mapped for salivary and/or urinary
      CA125 and CA130. On the background of such reference standards, OVX1 and M-CSF
      were assayed on 242 urine samples and 160 saliva samples provided by a 71-year
      old patient with a Mullerian/ovarian adenocarcinoma. Serum OVX1 correlates with
      serum CA125 (P = 0.002); when circulating CA125 concentrations decreased (from
      122 to 14 U/ml), the urinary excretion rate of OVX1 decreased (P = 0.005),
      whereas the urinary excretion rate of CA125 increased (P < 0.001). Salivary OVX1
      and urinary M-CSF show ultradian variations (with a frequency of one cycle in 14
      17 hours), which could be utilized to guide treatment timing targeted first to
      optimize treatment efficacy and as a second consideration to minimize treatment
      toxicity.

PMID- 8555444
TI  - Molecular cloning, characterization and expression analysis of two catalase
      isozyme genes in barley.
AB  - Clones representing two distinct barley catalase genes, Cat1 and Cat2, were found
      in a cDNA library prepared from seedling polysomal mRNA. Both clones were
      sequenced, and their deduced amino acid sequences were found to have high
      homology with maize and rice catalase genes. Cat1 had a 91% deduced amino acid
      sequence identity to CAT-1 of maize and 92% to CAT B of rice. Cat2 had 72 and 79%
      amino acid sequence identities to maize CAT-2 and -3 and 89% to CAT A of rice.
      Barley, maize or rice isozymes could be divided into two distinct groups by amino
      acid homologies, with one group homologous to the mitochondria-associated CAT-3
      of maize and the other homologous to the maize peroxisomal/glyoxysomal CAT-1.
      Both barley CATs contained possible peroxisomal targeting signals, but neither
      had favorable mitochondrial targeting sequences. Cat1 mRNA occurred in whole
      endosperms (aleurones plus starchy endosperm), in isolated aleurones and in
      developing seeds, but Cat2 mRNA was virtually absent. Both mRNAs displayed
      different developmental expression patterns in scutella of germinating seeds.
      Cat2 mRNA predominated in etiolated seedling shoots and leaf blades. Barley
      genomic DNA contained two genes for Cat1 and one gene for Cat2. The Cat2 gene was
      mapped to the long arm of chromosome 4, 2.9 cM in telomeric orientation from the
      mlo locus conferring resistance to the powdery mildew fungus (Erysiphe graminis
      f.sp. hordei).

PMID- 8555445
TI  - Fine structure and function of the osmotin gene promoter.
AB  - The gene encoding osmotin, a tobacco pathogenesis-related protein, has been shown
      to be regulated by an array of hormonal and environmental signals. The osmotin
      promoter fragment -248 to -108 upstream of the transcription start site (fragment
      A), was sufficient to direct reporter gene expression when fused to a minimal
      CaMV 35S promoter in transient assays using microprojectile bombardment. This was
      consistent with previous 5'-deletion analyses of the osmotin promoter which
      showed that the promoter sequence from -248 to -108 is absolutely required for
      reporter gene activity. Nuclear protein factors from salt-adapted tobacco cells,
      ABA-treated unadapted cells, and young cultured tobacco leaves were shown to
      interact with fragment A by gel mobility-shift assays. DNase I footprinting
      revealed that three conserved promoter elements in fragment A interact
      specifically with nuclear factors. These elements are: (1) a cluster of G-box
      like sequences (G sequence); (2) an AT-1 box-like sequence, 5'-AATTATTTTATG-3'
      (AT sequence); (3) a sequence highly conserved in ethylene-induced PR gene
      promoters, 5'-TAAGA/CGCCGCC-3' (PR sequence). Transient expression assays
      performed with fragment A deletions fused to GUS indicated that osmotin promoter
      activity correlated with the presence of these elements. UV cross-linking
      analysis showed that the protein complex bound to fragment A consisted of at
      least four individual proteins with approximate molecular masses of 28, 29, 40
      and 42 kDa. One component of this protein complex, which was associated with the
      G sequence, was a 14-3-3 like protein.

PMID- 8555446
TI  - A simplified procedure for the subtractive cDNA cloning of photoassimilate
      responding genes: isolation of cDNAs encoding a new class of pathogenesis-related
      proteins.
AB  - Transgenic tobacco plants (ppa-1) constitutively expressing Escherichia coli
      pyrophosphatase behind the 35S CaMV promoter accumulate high levels of soluble
      sugars in their leaves [27]. These plants were considered a tool to study
      adaptation of leaves to photoassimilate accumulation at the molecular level. By
      differential hybridization of a subtractive library enriched for transcripts
      present in the transgenic plants 12 different cDNAs were isolated. By sequence
      analysis four cDNAs could be identified as 1-aminocyclopropane-1-carboxylate
      oxidase and as three different pathogenesis-related proteins (PR-1b, PR-Q and SAR
      8.2). Two cDNAs were homologous to a calmodulin-like protein from Arabidopsis and
      a human ribosomal protein L19 while six cDNA clones remained unknown. One of
      these clones (termed PAR-1 for photoassimilate-responsive) displayed features
      similar to pathogenesis-related proteins: Hybridizing transcripts, 1.2 and 1.0 kb
      in length, were strongly inducible by salicylate and accumulated in tobacco
      plants after infection with potato virus Y (PVY) both in infected and uninfected
      systemic leaves. PAR-1 transcripts also accumulated in wildtype leaves upon
      floating on glucose and sucrose whereas sorbitol and polyethylene glycol had no
      effect. Rescreening of the ppa-1 cDNA library with the PAR-1 cDNA as probe
      resulted in 25 hybridizing cDNAs which by homology were found to fall into three
      classes (PAR-1a, b, c). The cDNAs coding for PAR-1a and b were 90.6% homologous
      on the DNA level while both were less related to the PAR-1c cDNA (70.5% and 75.2%
      homologous, respectively). One open reading frame was identified in all three PAR
      1 cDNA classes. Translation would result in proteins with a theoretical molecular
      mass of about 20 kDa. The N-terminal amino acid sequences resemble a signal
      peptide which would direct the proteins to the secretory pathway. Using selective
      3' hybridization probes of the three PAR-1 cDNAs it was possible to discriminate
      the different transcripts. Both PAR-1a and PAR-1c mRNAs are induced in plants
      treated with PVY.

PMID- 8555447
TI  - Functional analysis of isolated cpn10 domains and conserved amino acid residues
      in spinach chloroplast co-chaperonin by site-directed mutagenesis.
AB  - The possibilities of independent function of the two chaperonin 10 (cpn10)
      domains of the cpn10 homologue from spinach chloroplasts and the role of five
      conserved amino acid residues in the N-terminal cpn10 unit were investigated.
      Recombinant single domain proteins and complete chloroplast cpn10 proteins
      carrying amino acid exchanges of conserved residues in their N-terminal cpn10
      domain were expressed in Escherichia coli and partially purified. The function of
      the recombinant proteins was tested using GroEL as chaperonin 60 (cpn60) partner
      for in vitro refolding of denatured ribulose-1,5-bisphosphate carboxylase
      (Rubisco). Interaction with cpn60 was also monitored by the ability to inhibit
      GroEL ATPase activity. In vitro both isolated cpn10 domains were found to be
      incapable of co-chaperonin function. All mutants were also severely impaired in
      cpn10 function. The results are interpreted in terms of an essential role of the
      exchanged amino acid residues for the interaction between co-chaperonin and cpn60
      partner and in terms of a functional coupling of both cpn10 domains. To test the
      function of mutant chloroplast cpn10 proteins in vivo the cpn10 deficiency of E.
      coli strain CG712 resulting in an inability to assemble lambda-phage was
      exploited in a complementation assay. Transformation with plasmids directing the
      expression of mutant chloroplas cpn10 proteins in two cases restored lambda-phage
      assembly in this bacterial strain to the same extent as did transformation with a
      plasmid encoding wild-type cpn10 protein. In contrast a plasmid encoded third
      mutant and truncated forms of chloroplast cpn10 showed significantly reduced
      complementation efficiencies.

PMID- 8555448
TI  - Isolation, expression, and evolution of the gene encoding mitochondrial
      elongation factor Tu in Arabidopsis thaliana.
AB  - We have characterized a second nuclear gene (tufM) in Arabidopsis thaliana that
      encodes a eubacterial-like protein synthesis elongation factor Tu (EF-Tu). This
      gene does not closely resemble the previously described Arabidopsis nuclear tufA
      gene, which encodes the plastid EF-Tu, and does not contain sequence elements
      found in all cyanobacterial and plastid tufA genes. However, the predicted amino
      acid sequence includes an N-terminal extension which resembles an organellar
      targeting sequence and shares three unique sequence elements with mitochondrial
      EF-Tu's, from Saccharomyces cerevisiae and Homo sapiens, suggesting that this
      gene encodes the Arabidopsis mitochondrial EF-Tu. Consistent with this
      interpretation, the gene is expressed at a higher level in flowers than in
      leaves. Phylogenetic analysis confirms the mitochondrial character of the
      sequence and indicates that the human, yeast, and Arabidopsis tufM genes have
      undergone considerably more sequence divergence than their cytoplasmic
      counterparts, perhaps reflecting a cross-compartmental acceleration of gene
      evolution for components of the mitochondrial translation apparatus. As
      previously observed for tufA, the tufM gene is present in one copy in Arabidopsis
      but in several copies in other species of crucifers.

PMID- 8555449
TI  - Divergent evolution of two plastid genes, rbcL and atpB, in a non-photosynthetic
      parasitic plant.
AB  - Plastid DNA (ptDNA) regions for the large subunit of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubiso) (rbcL) and the beta-subunit of ATP synthase (atpB)
      genes of the holoparasite Lathraea clandestina L. were sequenced. These regions
      were obtained by cloning either a Bam HI endonuclease generated fragment from the
      Lathraea ptDNA or polymerase chain reaction (PCR) amplified products. The
      Lathraea ptDNA contains the entire sequence for the rbcL gene which shares 94.5%
      homology with the Nicotiana tabacum gene, whereas atpB is maintained as a
      pseudogene. The intergenic region between divergently transcribed rbcL and atpB
      genes is shorter (758 bp) in L. clandestina plastid genome in comparison with N.
      tabacum (823 bp), however they have a noticeable similarity, mainly in the rbcL
      5'-upstream region. A low level of the rbcL gene transcription was detected
      whereas no atpB transcripts were found in Latraea. The plasmid rbcL gene of the
      hemiparasite Melampyrum pratense and the autotroph Digitalis purpurea both from
      the Scrophulariaceae were cloned by PCR amplification and then sequenced. The L.
      clandestina rbcL gene is highly homologous to the M. pratense and D. purpurea
      genes. The data indicate that the evolution of the plastid atpB-rbcL region was
      different in parasites from the Scrophulariaceae and Orobanchaceae families.

PMID- 8555450
TI  - Physical map and gene organization of the mitochondrial genome from the
      unicellular green alga Platymonas (Tetraselmis) subcordiformis (Prasinophyceae).
AB  - The entire mitochondrial genome (mt genome) of the unicellular green alga
      Platymonas subcordiformis (synonym Tetraselmis subcordiformis; Prasinophyceae)
      was cloned and a physical map for the four restriction enzymes Hind III, Eco RI,
      Bg/II and Xba I was constructed. The mt genome of P. subcordiformis is a 42.8 kb
      circular molecule, coding for at least 23 genes. Hybridization and sequence
      analysis revealed the presence of a ca. 1.5 kb inverted repeat on the mt genome
      of P. subcordiformis. Phylogenetic analyses based on sequences of several coxI
      genes were carried out. Our data indicate that mitochondria from P.
      subcordiformis and from land plants form a natural, monophyletic group.

PMID- 8555451
TI  - Post-transcriptional regulation of bifunctional alpha-amylase/subtilisin
      inhibitor expression in barley embryos by abscisic acid.
AB  - Changes in bifunctional alpha-amylase/subtilisin inhibitor (BASI) expression
      induced by abscisic acid (ABA) were studied using in vitro cultured barley
      (Hordeum vulgare cv. Bonanza) embryos. The steady-state levels of BASI mRNA and
      BASI protein were increased by exogenously applied ABA. Accumulation of BASI
      protein was preceded by an increase in message level. The results suggest that
      ABA does not affect BASI mRNA translation. Nuclear run-on assays demonstrated
      that ABA had no effect on transcriptional activity. BASI mRNA was not detectable
      in the embryos treated with a protein synthesis inhibitor, cycloheximide, which
      had no inhibitory effect on BASI transcription rate. We propose that ABA
      increases the stability of BASI mRNA through synthesis of a short-lived protein
      that protects the message.

PMID- 8555452
TI  - Constitutive expression of small heat shock proteins in vegetative tissues of the
      resurrection plant Craterostigma plantagineum.
AB  - Using antibodies raised against two sunflower small heat shock proteins (sHSPs),
      we have detected immunologically related proteins in unstressed vegetative
      tissues from the resurrection plant Craterostigma plantagineum. In whole plants,
      further accumulation of these polypeptides was induced by heat-shock or water
      stress. In desiccation-intolerant Craterostigma callus tissue, we failed to
      detect sHSP-related polypeptides, but their expression, and the concurrent
      acquisition of desiccation tolerance was induced by exogenous abscisic acid (ABA)
      treatment. In untressed plants, the cross-reacting polypeptides were abundant in
      the roots and lower part of the shoots, where they showed homogeneous tissue
      distributions. This constitutive expression is novel for vegetative tissues of
      higher plants, and resembles the expression patterns of sHSPs in desiccation
      tolerant zygotic embryos and germinating seeds.

PMID- 8555453
TI  - Regulation of expression of the cucumber isocitrate lyase gene in cotyledons upon
      seed germination and by sucrose.
AB  - A 6.5 kb cucumber genomic DNA fragment containing the icl gene was introduced
      into Nicotiana plumbaginifolia and shown to direct isocitrate lyase (ICL) mRNA
      synthesis in transgenic seedlings upon germination, in a temporally regulated
      manner. Two putative icl promoter fragments, of 2900 and 572 bp, were
      subsequently linked to the GUS reporter gene and introduced into N.
      plumbaginifolia. Both constructs directed GUS expression after transgenic seed
      germination, and although the 572 bp fragment gave only 1% of the activity of the
      2900 bp fragment, it directed expression in the same cotyledon-specific and
      temporally regulated pattern. Seedlings were transferred to darkness after 18
      days growth in the light, to induce a starvation response. The 2900 bp construct
      was activated by starvation and repressed by exogenous sucrose, whereas the 572
      bp construct was not starvation-responsive. To localize the region of the 2900 bp
      promoter fragment which is responsible for regulation by sucrose, further
      deletions were made, linked to GUS, and assayed in a cucumber protoplast
      transient assay system. Constructs with promoters of 2900, 2142 and 1663 bp were
      activated by starvation and repressed by sucrose, but promoters of 1142 and 572
      bp showed no such response. We conclude that the icl gene promoter contains at
      least two distinct cis-acting elements, one required for the response to sucrose
      and the other which participates in expression upon seed germination.

PMID- 8555454
TI  - Transformation of Synechococcus with a gene for choline oxidase enhances
      tolerance to salt stress.
AB  - Choline oxidase, isolated from the soil bacterium Arthrobacter globiformis,
      converts choline to glycinebetaine (N-trimethylglycine) without a requirement for
      any cofactors. The gene for this enzyme, designated codA, was cloned and
      introduced into the cyanobacterium Synechococcus sp. PCC 7942. The codA gene was
      expressed under the control of a strong constitutive promoter, and the
      transformed cells accumulated glycinebetaine at intracellular levels of 60-80 mM.
      Consequently the cells acquired tolerance to salt stress, as evaluated in terms
      of growth, accumulation of chlorophyll and photosynthetic activity.

PMID- 8555455
TI  - Production of the AVR9 elicitor from the fungal pathogen Cladosporium fulvum in
      transgenic tobacco and tomato plants.
AB  - Three constructs were used to study the expression of the avirulence gene Avr9
      from the fungal tomato pathogen Cladosporium fulvum in plants. They include
      pAVIR1, pAVIR2 and pAVIR21, encoding the wild-type AVR9 protein and two hybrid
      AVR9 proteins containing the signal sequences of the pathogenesis-related
      proteins PR-S and PR-1a, respectively. Transgenic tobacco plants obtained with
      the three constructs showed a normal phenotype and produced AVR9 elicitor with
      the same specific necrosis-inducing activity as the wild-type AVR9 elicitor
      produced in planta by isolates of C. fulvum containing the Avr9 gene. Level of
      expression was not correlated with number of T-DNA integrations, but plants
      homozygous for the Avr9 gene produced more elicitor protein than heterozygous
      plants. The amino acid sequence of the processed AVR9 peptide present in
      apoplastic fluid (AF) of pAVIR1 transformed plants producing the wild-type AVR9
      elicitor was identical to that of the wild-type AVR9 peptide isolated from C.
      fulvum-infected tomato leaves. Transgenic Cf0 genotypes of tomato, obtained by
      transformation with construct pAVIR21, showed a normal phenotype. However,
      transgenic F1 plants expressing the Avr9 gene, obtained from crossing transgenic
      Cf0 genotypes with wild-type Cf9 genotypes, showed delayed growth, necrosis and
      complete plant death indicating that the AVR9 peptide produced in plants carrying
      the Cf9 gene is deleterious. The necrotic defence response observed in Cf9
      genotypes expressing the Avr9 gene support the potential to apply avirulence
      genes in molecular resistance breeding.

PMID- 8555456
TI  - Nuclear mutants of Chlamydomonas reinhardtii defective in the biogenesis of the
      cytochrome b6f complex.
AB  - The random integration of transforming DNA into the nuclear genome of
      Chlamydomonas has been employed as an insertional mutagen to generate a
      collection of photosynthetic mutants that display abnormal steady-state
      fluorescence levels and an acetate-requiring phenotype. Electron paramagnetic
      resonance spectroscopy was then used to identify those mutants that specifically
      lack a functional cytochrome b6f complex. Our analysis of RNA and protein
      synthesis in five of these mutants reveals four separate phenotypes. One mutant
      fails to accumulate transcript for cytochrome f, whilst a second displays a
      severely reduced accumulation of the cytochrome b6 transcript. Two other mutants
      appear to be affected in the insertion of the haem co-factor into cytochrome b6.
      The fifth mutant displays no detectable defect in the synthesis of any of the
      known subunits of the complex. Genetic analysis of the mutants demonstrates that
      in three cases, the mutant phenotype co-segregates with the introduced DNA. For
      the mutant affected in the accumulation of the cytochrome f transcript, we have
      used the introduced DNA as a tag to isolate the wild-type version of the affected
      gene.

PMID- 8555457
TI  - Light-dependent chlorophyll a biosynthesis upon chlL deletion in wild-type and
      photosystem I-less strains of the cyanobacterium Synechocystis sp. PCC 6803.
AB  - Part of the chlL gene encoding a component involved in light-independent
      protochlorophyllide reduction was deleted in wild type and in a photosystem I
      less strain of Synechocystis sp. PCC 6803. In resulting mutants, chlorophyll
      biosynthesis was fully light-dependent. When these mutants were propagated under
      light-activated heterotrophic growth conditions (in darkness except for 15 min of
      weak light a day) for several weeks, essentially no chlorophyll was detectable
      but protochlorophyllide accumulated. Upon return of the chlL- mutant cultures to
      continuous light, within the first 6 h chlorophyll was synthesized at the expense
      of protochlorophyllide at a rate independent of the presence of photosystem I.
      Chlorophyll biosynthesized during this time gave rise to a 685 nm fluorescence
      emission peak at 77 K in intact cells. This peak most likely originates from a
      component different from those known to be directly associated with photosystems
      II and I. Development of 695 and 725 nm peaks (indicative of intact photosystem
      II and photosystem I, respectively) required longer exposures to light. After 6 h
      of greening, the rate of chlorophyll synthesis slowed as protochlorophyllide was
      depleted. In the chlL- strain, greening occurred at the same rate at two
      different light intensities (5 and 50 microE m-2 s-1), indicating that also at
      low light intensity the amount of light is not rate-limiting for
      protochlorophyllide reduction. Thus, in this system the rate of chlorophyll
      biosynthesis is limited neither by biosynthesis of photosystems nor by the light
      dependent protochlorophyllide reduction. We suggest the presence of a chlorophyll
      binding 'chelator' protein (with 77 K fluorescence emission at 685 nm) that binds
      newly synthesized chlorophyll and that provides chlorophyll for newly synthesized
      photosynthetic reaction centers and antennae.

PMID- 8555458
TI  - Organization and expression of the gene coding for the potassium transport system
      AKT1 of Arabidopsis thaliana.
AB  - We have isolated and sequenced the genomic clone coding for the potassium
      transport system AKT1 of Arabidopsis thaliana. Southern blot analysis indicated
      that the gene is present in one copy in the Arabidopsis genome. The coding
      sequence is interrupted by ten introns. Sequence comparisons of AKT1 polypeptide
      with the voltage-gated inward rectifying Arabidopsis K+ channel KAT1, and with
      voltage- or cyclic nucleotide-gated channels from insects and mammals, revealed a
      highly conserved domain found specifically in both plant polypeptides, and
      corresponding to about the last 50 amino acids of their C-terminal region.
      Northern blot analysis of AKT1 expression in Arabidopsis seedlings indicated that
      AKT1 is preferentially expressed in roots. No transcript was detected in extracts
      from heterotrophic suspension culture cells. Depleting K+ in the Arabidopsis
      seedling culture medium for 4 days led to a strong decrease in K+ tissue content
      (ca. 50%), but did not affect AKT1 transcript level.

PMID- 8555459
TI  - Characterization of tobacco plants expressing a bacterial salicylate hydroxylase
      gene.
AB  - Transgenic tobacco plants that express the bacterial nahG gene encoding
      salicylate hydroxylase have been shown to accumulate very little salicylic acid
      and to be defective in their ability to induce systemic acquired resistance
      (SAR). In recent experiments using transgenic NahG tobacco and Arabidopsis
      plants, we have also demonstrated that salicylic acid plays a central role in
      both disease susceptibility and genetic resistance. In this paper, we further
      characterize tobacco plants that express the salicylate hydroxylase enzyme. We
      show that tobacco mosaic virus (TMV) inoculation of NahG tobacco leaves induces
      the accumulation of the nahG mRNA in the pathogen infected leaves, presumably due
      to enhanced stabilization of the bacterial mRNA. SAR-associated genes are
      expressed in the TMV-infected leaves, but this is localized to the area
      surrounding necrotic lesions. Localized acquired resistance (LAR) is not induced
      in the TMV-inoculated NahG plants suggesting that LAR, like SAR, is dependent on
      SA accumulation. When SA is applied to nahG-expressing leave's SAR gene
      expression does not result. We have confirmed earlier reports that the salicylate
      hydroxylase enzyme has a narrow substrate specificity and we find that catechol,
      the breakdown product of salicylic acid, neither induces acquired resistance nor
      prevents the SA-dependent induction of the SAR genes.

PMID- 8555461
TI  - Transcription of tobacco phytochrome-A genes initiates at multiple start sites
      and requires multiple cis-acting regulatory elements.
AB  - Promoter regions of the Nicotiana tabacum PHYA1 and PHYA2 genes display 89%
      sequence identity. Analysis of the 5' ends of both the PHYA1 and the PHYA2
      transcript revealed multiple, distinct mRNA species, each differing in length and
      in abundance. The levels of the major PHYA1, PHYA2 transcripts were found to be
      auto-regulated by phytochrome. This auto-regulation was most efficient in 2-8-day
      old seedlings. Furthermore, we examined the expression pattern of the PHYA1-GUS
      reporter gene, containing a 4700 bp PHYA1 promoter fragment or its 5'-deletion
      derivatives, by GUS histochemistry and by RNase protection assays in transgenic
      tobacco plants. Our data indicate that the PHYA1 promoter contains three regions
      which are necessary for the maximum level and regulated expression. We show that
      a 264 bp promoter fragment contains a cis-regulatory element(s) responsible for
      expression in the root tips of transgenic seedlings. The major cis-regulatory
      elements required for high-level transcription and expression in other organs are
      located in separate regions of the PHYA1 promoter. These data indicate the
      contribution of multiple cis-regulatory elements for the maximum and regulated
      expression of tobacco genes coding for phytochrome A protein.

PMID- 8555460
TI  - The expression of an abundant transmitting tract-specific endoglucanase (Sp41) is
      promoter-dependent and not essential for the reproductive physiology of tobacco.
AB  - In angiosperms the interactions between the secretory matrix of the stylar
      transmitting tract and the growing pollen tubes have central roles in determining
      a successful fertilization. Sp41 is a major glycosylated component of the soluble
      proteins of the transmitting tract matrix and exhibits (1-3)-beta-glucanase
      activity. It is a member of the pathogenesis-related protein superfamily, but
      shows developmental regulation as opposed to pathogen induction. In order to
      investigate the mechanisms regulating Sp41 expression, we isolated and
      characterized genomic clones corresponding to the sp41 alpha gene. Sp41 alpha
      contains an intervening sequence localized between the sequences encoding for a
      putative signal peptide and the mature protein. A fragment of 2.5 kb that lies 5'
      to the coding region of the gene was sufficient to confer transmitting tract
      specific expression to a beta-glucuronidase reporter gene in transgenic tobacco
      plants. The sp41 transcripts have unusually long 5'-untranslated sequences. The
      leader sequences contain small open reading frames, include secondary structures,
      and may be involved in post-transcriptional regulation. A possible function for
      Sp41 in reproductive physiology was tested by monitoring tobacco plants
      transformed with antisense stylar sp41 alpha RNA: Transgenic antisense plants
      with immunologically and enzymatically undetectable levels of (1-3)-beta
      glucanase were obtained and their offspring analyzed. The progeny plants did not
      show any detectable phenotypic modifications as they had a normal flower
      morphology and were fully fertile.

PMID- 8555462
TI  - Definition of constitutive gene expression in plants: the translation initiation
      factor 4A gene as a model.
AB  - The NeIF-4A10 gene belongs to a family of at least ten genes, all of which encode
      closely related isoforms of translation initiation factor 4A. The promoter region
      of NeIF-4A10 was sequenced, and four mRNA 5' ends were determined. Deletions
      containing 2750, 689 and 188 bp of untranscribed upstream DNA were fused to the
      GUS reporter gene and introduced into transgenic tobacco. The three constructs
      mediated GUS expression in all cells of the leaf, stem and shoot apical meristem.
      Control experiments using in situ hybridization and tissue printing indicated
      that the observed GUS expression matches the expression patterns of NeIF-4A mRNA
      and protein. This detailed analysis at the level of mRNA, protein and reporter
      gene expression shows that NeIF-4A10 is an ideal constitutively expressed control
      gene. We argue that inclusion of such a control gene in experiments dealing with
      specifically expressed genes is in many cases essential for the correct
      interpretation of observed expression patterns.

PMID- 8555463
TI  - Leukemia and lymphoma in ataxia telangiectasia.
AB  - There is a large increase in lymphoid malignancy in A-T patients and a total
      absence of myeloid tumors. Penetrance of the tumor phenotype is about 10% to 15%
      by early adulthood. The increase in lymphoid malignancy includes both B- and T
      cell tumors. However, young A-T patients do not show an increased susceptibility
      to cALL, and the UK data suggest that B-cell lymphoma occurs in older A-T
      children. T-cell tumors may occur at any age and may be T-ALL, T-cell lymphoma,
      or T-PLL; most strikingly, there may be a fourfold to fivefold increased
      frequency of T-cell tumors compared with that of B-cell tumors in these patients.
      If this is correct, it is possible that a significant proportion of all T-ALL/T
      cell lymphoma in infants might be associated with undiagnosed A-T. The age range
      and sex predominance for T-ALL may be different for A-T and non-A-T patients and
      the age range for T-PLL may also be different in A-T and non-A-T patients. There
      is clearly some uncertainty concerning the ratio of T-cell to B-cell tumors in A
      T, but this could be clarified by the publication of all tumors that occur in the
      disorder. In contrast, 8 of 9 tumors reported in NBS, which shows the same
      cellular features as A-T, were lymphomas and none was a leukemia. There are
      several indicators of genetic heterogeneity in A-T that suggest that not all
      patients are equally susceptible to all T-cell tumor types. Concordance for tumor
      type within individual families suggests that particular gene defects may be
      associated with particular tumor types. The logical extrapolation of this
      argument is that some patients may not have any increased risk for B-cell tumors
      at all or even to all T-cell types but only to a particular type of T-cell tumor.
      What is the cause of the increased predisposition to leukemia/lymphoma in A-T
      patients? There is no evidence that the immunodeficiency in A-T is related to
      this predisposition. One of the major findings in all A-T patients is the
      increase in V(D)J-mediated chromosome rearrangement observed in T lymphocytes.
      Particular chromosome translocations in T cells, involving a break in a TCR gene,
      are characteristically associated with either T-ALL or T-PLL in non-A-T patients.
      The majority of T-cell tumors in A-T are T-ALL and T-cell lymphoma, about which
      virtually nothing is known chromosomally, and the assumption is that the
      increased number of translocations leads to the increased level of these tumors.
      In older T patients, the expansion of specific translocation T-cell clones has
      been followed to the point to which they develop into T-PLL. All the evidence,
      therefore, suggests that the A-T mutation in the homozygous state allows a large
      increase in production of translocations formed at the time of V(D)J
      recombination, and this leads to the increased predisposition to leukemia. The
      general increased predisposition to T-cell tumors compared with B-cell tumors in
      A-T patients may be related to a preferential occurrence of translocations in T
      cells. Relatively little is known about translocations in circulating B
      lymphocytes in normal individuals, but A-T siblings have been shown to have
      clonal chromosome rearrangements of both B and T cells, simultaneously, although
      in these siblings the T-cell clones occupied all the T-cell compartment and the B
      cell clones were small. An important inference from these facts is that the A-T
      defect preferentially affects immune system gene recombination in T cells rather
      than B cells. Recent evidence suggests that the V(D)J recombination machinery is
      not identical or is not regulated identically in T- and B-cell progenitors. This
      finding is consistent with the hypothesis that V(D)J rejoining in the majority,
      at least, of A-T patients may be preferentially deficient in T cells compared
      with B cells giving rise to the greatly increased number of translocations and T
      cell tumors. Carbonari et al proposed that the recombination defect in A-T cells
      affected both Ig isotype switching and TCR rearrangeme

PMID- 8555465
TI  - Developmental regulation of myeloid gene expression and demethylation during ex
      vivo culture of peripheral blood progenitor cells.
AB  - Expression of tissue- and development-specific genes is coordinately regulated
      during maturation of hematopoietic precursor cells toward functional, end-stage
      peripheral blood (PB) cells. To study the expression and methylation of several
      myeloid-specific genes during in vitro differentiation of normal hematopoietic
      progenitor cells, we used a model of CD34+ selected PB progenitor cells (PBPCs).
      PBPCs from six patients with solid tumors were recruited by standard-dose
      chemotherapy and subsequent administration of recombinant granulocyte colony
      stimulating factor (G-CSF). PBPCs were collected and CD34+ cells selected by
      immunoadsorption columns using a biotinylated anti-CD34 monoclonal antibody.
      Enriched cells contained between 78% and 90% (median, 84%) CD34+ cells as
      determined by fluorescence-activated cell sorting analysis. Cell preparations
      were cultured in the presence of interleukin-1 beta (IL-1 beta), IL-3, IL-6 and
      stem cell factor and with or without G-CSF for various time intervals up to 20
      days. Genes for CD34 surface antigen, lysozyme (LZM) and myeloperoxidase (MPO)
      were examined by RNA and DNA analyses. A rapid and early downregulation of CD34
      transcripts was observed, with concomitant, time-dependent upregulation of
      expression of both the LZM and MPO genes. These effects were enhanced in the
      presence of G-CSF. Analysis of the DNA methylation status at key sites within
      these genes showed a pattern of differentiation- and expression-associated
      demethylation of the LZM gene, which was also enhanced by G-CSF, and constitutive
      and unaltered demethylation at key regions of the CD34 and MPO genes. In
      conclusion, the genes for CD34, LZM, and MPO are regulated during in vitro
      culture of very immature PBPCs in the presence of stem cell factor, IL-1, IL-3,
      IL-6; their effects are enhanced by G-CSF.

PMID- 8555464
TI  - Thrombopoietin induces tyrosine phosphorylation of Stat3 and Stat5 in human blood
      platelets.
AB  - Thrombopoietin is known to be essential for megakaryocytopoiesis and
      thrombopoiesis. Recently, we and others have shown that thrombopoietin induces
      rapid tyrosine phosphorylation of Jak2 and other proteins in human platelets and
      BaF3 cells, genetically engineered to express c-Mpl, a receptor for
      thrombopoietin. The Jak family of tyrosine kinases are known to mediate some of
      the effects of cytokines or hematopoietic growth factors by recruitment and
      tyrosine phosphorylation of a variety of Stat (signal transducers and activators
      of transcription) proteins. Hence, we have investigated whether Stat proteins are
      present in platelets and, if so, whether they become tyrosine phosphorylated in
      response to thrombopoietin. We immunologically identified Stat1, Stat2, Stat3,
      and Stat5 in human platelet lysates. Thrombopoietin induced tyrosine
      phosphorylation of Stat3 and Stat5 in these cells. Thrombopoietin also induced
      tyrosine phosphorylation of Stat3 and Stat5 in FDCP-2 cells genetically
      engineered to constitutively express human c-Mpl. Thus, our data indicate that
      Stat3 and Stat5 may be involved in signal transduction after ligand binding to c
      Mpl and that this event may have a role in megakaryopoiesis/thrombopoiesis or
      possibly a mature platelet function such as aggregation.

PMID- 8555466
TI  - Rapid and efficient selection of human hematopoietic cells expressing murine heat
      stable antigen as an indicator of retroviral-mediated gene transfer.
AB  - Recombinant retroviruses offer many advantages for the genetic modification of
      human hematopoietic cells, although their use in clinical protocols has thus far
      given disappointing results. There is therefore an important need to develop new
      strategies that will allow effectively transduced primitive hematopoietic target
      populations to be both rapidly characterized and isolated free of residual
      nontransduced but biologically equivalent cells. To address this need, we
      constructed a murine stem cell virus (MSCV)-based retroviral vector containing
      the 228-bp coding sequence of the murine heat-stable antigen (HSA) and generated
      helper virus-free amphotropic MSCV-HSA producer cells by transfection of GP-env
      AM12 packaging cells. Light density and, in some cases, lineage marker-negative
      (lin-) normal human marrow or mobilized peripheral blood cells preactivated by
      exposure to interleukin-3 (IL-3), IL-6, and Steel factor in vitro for 48 hours
      were then infected by cocultivation with these MSCV-HSA producer cells for a
      further 48 hours in the presence of the same cytokines. Fluorescence-activated
      cell sorting (FACS) analysis of the cells 24 hours later showed 21% to 41% (mean,
      27%) of those that were still CD34+ to have acquired the ability to express HSA.
      The extent of gene transfer to erythroid and granulopoietic progenitors (burst
      forming unit-erythroid and colony-forming unit-granulocyte-macrophage), as
      assessed by the ability of these cells to form colonies of mature progeny in the
      presence of normally toxic concentrations of G418, averaged 11% and 12%,
      respectively, in 6 experiments. These values could be increased to 100% and 77%,
      respectively, by prior isolation of the CD34+HSA+ cell fraction and were
      correspondingly decreased to an average of 2% and 5%, respectively, in the
      CD34+HSA- cells. In addition, the extent of gene transfer to long-term culture
      initiating cells (LTC-IC) was assessed by G418 resistance. The average gene
      transfer to LTC-IC-derived colony-forming cells in the unsorted population was <
      or = 7% in 4 experiments. FACS selection of the initially CD34+HSA+ cells
      increased this value to 86% and decreased it to 3% for the LTC-IC plated from the
      CD34+HSA- cells. Transfer of HSA gene expression to a phenotypically defined more
      primitive subpopulation of CD34+ cells, ie, those expressing little or no CD38,
      could also be shown by FACS analysis of infected populations 24 hours after
      infection. These findings underscore the potential use of retroviral vectors
      encoding HSA for the specific identification and non-toxic selection immediately
      after infection of retrovirally transduced populations of primitive human
      hematopoietic cells. In addition, such vectors should facilitate the subsequent
      tracking of their marked progeny using multiparameter flow cytometry.

PMID- 8555468
TI  - Targeted gene transfer to human hematopoietic progenitor cell lines through the c
      kit receptor.
AB  - In this report, we describe a novel gene therapy approach for hematopoietic
      stem/progenitor cells using a specific receptor-mediated gene transfection
      procedure to target c-kit+ cell lines. The vector consists of plasmid DNA
      containing a luciferase reporter gene that is condensed by electrostatic forces
      with polylysine (PL) covalently linked to streptavidin (binds biotinylated
      ligand) and PL covalently linked to adenovirus (AD; to achieve endosomal lysis)
      with the final addition of biotinylated steel factor (SLF-biotin). Targeted
      transfection of growth factor-dependent hematopoietic progenitor cell lines that
      express c-kit showed specific luciferase gene expression over cell lines that did
      not express c-kit. This effect was dependent on the dose of SLF-biotin and was
      competed by excess SLF or with monoclonal antibodies that recognize c-kit and
      block the binding of SLF to its receptor. Maximum transfection efficiency (> 90%)
      requires a 2-hour incubation period of the vector with the cells, and maximum
      gene expression occurred 30 hours later. Removal of the endosomalytic agent, AD,
      from the vector resulted in the loss of gene expression. Vector targeting was
      versatile and could be changed by the addition of other biotinylated ligands. In
      principle, this vector should be broadly applicable to deliver genes to
      hematopoietic stem/progenitor cells in vitro and in vivo.

PMID- 8555467
TI  - Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte
      predominance Hodgkin's disease.
AB  - The BCL-6 gene encoding a nuclear-located Kruppel-type zinc finger protein is
      rearranged in about 30% diffuse large B-cell lymphomas and is expressed
      predominantly in normal germinal center B cells and related lymphomas. These
      findings suggest that BCL-6 may play a role in regulating differentiation of
      normal germinal center B cells and that its deregulated expression caused by
      rearrangements may contribute to lymphomagenesis. This prompted us to investigate
      the expression of the BCL-6 protein in Hodgkin's disease (HD), focusing on the
      nodular lymphocyte predominance subtype (NLPHD), which differs from classical HD
      by virtue of the B-cell nature of the malignant cell population (so-called L&H
      cells) and its relationship with germinal centers. Forty-one HD samples (19
      NLPHD, 12 nodular sclerosis, and 10 mixed cellularity) were immunostained with
      the monoclonal antibodies PG-B6 and PG-B6p that react with a fixative-sensitive
      and a formalin-resistant epitope on the aminoterminal region of the BCL-6 gene
      product, respectively. Strong nuclear positivity for the BCL-6 protein was
      detected in tumor (L&H) cells in all cases of NLPHD. In contrast, BCL-6 was
      expressed only in a small percentage of Hodgkin and Reed-Sternberg cells in about
      30% of classical HD cases. Notably, the nuclei of reactive CD3+/CD4+ T cells
      nearby to and rosetting around L&H cells in NLPHD were also strongly BCL-6+, but
      lacked CD40 ligand (CD40L) expression. This staining pattern clearly differed
      from that of classical HD, whose cellular background was made up of CD3+/CD4+ T
      cells showing the BCL-6-/CD40L+ phenotype. These results further support the
      concept that NLPHD is an histogenetically distinct, B-cell-derived subtype of HD
      and suggest a role for BCL-6 in its development.

PMID- 8555469
TI  - Hematopoietic defects in mice lacking the sialomucin CD34.
AB  - Although the pluripotent hematopoietic stem cell can only be definitively
      identified by its ability to reconstitute the various mature blood lineages, a
      diversity of cell surface antigens have also been specifically recognized on this
      subset of hematopoietic progenitors. One such stem cell-associated antigen is the
      sialomucin CD34, a highly O-glycosylated cell surface glycoprotein that has also
      been shown to be expressed on all vascular endothelial cells throughout murine
      embryogenesis as well as in the adult. The functional significance of CD34
      expression on hematopoietic progenitor cells and developing blood vessels is
      unknown. To analyze the involvement of CD34 in hematopoiesis, we have produced
      both embryonic stem (ES) cells and mice that are null for the expression of this
      mucin. Analysis of yolk saclike hematopoietic development in embryoid bodies
      derived from CD34-null ES cells showed a significant delay in both erythroid and
      myeloid differentiation that could be reversed by transfection of the mutant ES
      cells with CD34 constructs expressing either a complete or truncated cytoplasmic
      domain. Measurements of colony-forming activity of hematopoietic progenitor cells
      derived from yolk sacs or fetal livers isolated from CD34-null embryos also
      showed a decreased number of these precursor cells. In spite of these diminished
      embryonic hematopoietic progenitor numbers, the CD34-null mice developed
      normally, and the hematopoietic profile of adult blood appeared typical. However,
      the colony-forming activity of hematopoietic progenitors derived from both bone
      marrow and spleen is significantly reduced in adult CD34-deficient animals, and
      these CD34-deficient progenitors also appear to be unable to expand in liquid
      cultures in response to hematopoietic growth factors. Even with these apparent
      progenitor cell deficiencies, CD34-null animals showed kinetics of erythroid,
      myeloid, and platelet recovery after sublethal irradiation that are
      indistinguishable from wild-type mice. These data strongly suggest that CD34
      plays an important role in the formation of progenitor cells during both
      embryonic and adult hematopoiesis. However, the hematopoietic sites of adult CD34
      deficient mice may still have a significant reservoir of progenitor cells that
      allows for normal recovery after nonmyeloablative peripheral cell depletion.

PMID- 8555470
TI  - Complete remission in severe aplastic anemia after high-dose cyclophosphamide
      without bone marrow transplantation.
AB  - Severe aplastic anemia (SAA) can be successfully treated with allogeneic bone
      marrow transplantation (BMT) or immunosuppressive therapy. However, the majority
      of patients with SAA are not eligible for BMT because they lack an HLA-identical
      sibling. Conventional immunosuppressive therapy also has major limitations; many
      of its remissions are incomplete and relapse or secondary clonal disease is
      common. Cyclophosphamide is a potent immunosuppressive agent that is used in all
      BMT conditioning regimens for patients with SAA. Preliminary evidence suggested
      that high-dose cyclophosphamide, even without BMT, may be beneficial to patients
      with SAA. Therefore, 10 patients with SAA and lacking an HLA-identical sibling
      were treated with high-dose cyclophosphamide (45 mg/kg/d) for 4 consecutive days
      with or without cyclosporine. A complete response (hemoglobin level, > 13 g/dL;
      absolute neutrophil count, > 1.5 x 10(9)/L, and platelet count > 125 x 10(9)/L)
      was achieved in 7 of the 10 patients. One of the complete responders died from
      the acquired immunodeficiency syndrome 44 months after treatment with high-dose
      cyclophosphamide. The 6 remaining patients are alive and in continuous complete
      remission, with a median follow-up of 10.8 years (range, 7.3 to 17.8 years). The
      median time to last platelet transfusion and time to 0.5 x 10(9) neutrophils/L
      were 85 and 95 days, respectively. None of the complete responders has relapsed
      or developed a clonal disease. These results suggest that high-dose
      cyclophosphamide, even without BMT, may be more effective than conventional
      immunosuppressive therapy in restoring normal hematopoiesis and preventing
      relapse or secondary clonal disorders. Hence, further studies confirming the
      efficacy of this approach in SAA are indicated.

PMID- 8555471
TI  - Improved outcome in adult B-cell acute lymphoblastic leukemia.
AB  - A total of 68 adult patients with B-cell acute lymphoblastic leukemia (B-ALL)
      were treated in three consecutive adult multicenter ALL studies. The diagnosis of
      B-ALL was confirmed by L3 morphology and/or by surface immunoglobulin (Slg)
      expression with > 25% blast cell infiltration in the bone marrow (BM). They were
      characterized by male predominance (78%) and a median age of 34 years (15 to 65
      y) with only 9% adolescents (15 to 20 y), but 28% elderly patients (50 to 65 y).
      The patients received either a conventional (N = 9) ALL treatment regimen (ALL
      study 01/81) or protocols adapted from childhood B-ALL with six short, intensive
      5-day cycles, alternately A and B. In study B-NHL83 (N = 24) cycle A consisted of
      fractionated doses of cyclophosphamide 200 mg/m2 for 5 days, intermediate-dose
      methotrexate (IdM) 500 mg/m2 (24 hours), in addition to cytarabine (AraC),
      teniposide (VM26) and prednisone. Cycle B was similar except that AraC and VM26
      were replaced by doxorubicin. Major changes in study B-NHL86 (N = 35) were
      replacement of cyclophosphamide by ifosphamide 800 mg/m2 for 5 days, an increase
      of IdM to high-dose, 1,500 mg/m2 (HdM) and the addition of vincristine. A
      cytoreductive pretreatment with cyclophosphamide 200 mg/m2, and prednisone 60
      mg/m2, each for 5 days was recommended in study B-NHL83 for patients with high
      white blood cell (WBC) count (> 2,500/m2) or large tumor burden and was
      obligatory for all patients in study B-NHL86. Central nervous system (CNS)
      prophylaxis/treatment consisted of intrathecal methotrexate (MTX) therapy, later
      extended to the triple combination of MTX, AraC, and dexamethasone, and a CNS
      irradiation (24 Gy) after the second cycle. Compared with the ALL 01/81 study
      where all the patients died, results obtained with the pediatric protocols B
      NHL83 and B-NHL86 were greatly improved. The complete remission (CR) rates
      increased from 44% to 63% and 74%, the probability of leukemia free survival
      (LFS) from 0% to 50% and 71% (P = .04), and the overall survival rates from 0% to
      49% and 51% (P = .001). Toxicity, mostly hematotoxicity and mucositis, was severe
      but manageable. In both studies B-NHL83 and B-NHL86, almost all relapses occurred
      within 1 year. The time to relapse was different for BM, 92 days, and for
      isolated CNS and combined BM and CNS relapses, 190 days (P = .08). The overall
      CNS relapses changed from 50% to 57% and 17%, most probably attributable to the
      high-dose MTX and the triple intrathecal therapy. LFS in studies B-NHL83 and B
      NHL86 was significantly influenced by the initial WBC count < or > 50,000/microL,
      LFS 71% versus 29% (P = .003) and hemoglobin value > or < 8 g/dL, LFS 67% versus
      27% (P = .02). Initial CNS involvement had no adverse impact on the outcome.
      Elderly B-ALL patients (> 50 years) also benefited from this treatment with a CR
      rate of 56% and a LFS of 56%. It is concluded that this short intensive therapy
      with six cycles is effective in adult B-ALL. HdM and fractionated higher doses of
      cyclophosphamide or ifosphamide seem the two major components of treatment.

PMID- 8555472
TI  - High-frequency cell surface expression of a foreign protein in murine
      hematopoietic stem cells using a new retroviral vector.
AB  - A retroviral vector (pSFF) derived from murine Friend spleen focus forming virus
      was used to transduce murine hematopoietic stem cells and express a cell surface
      marker protein, mutated murine prion protein, in vitro and in vivo after
      transplantation. To enhance retroviral vector integration in bone marrow cells,
      mice were treated with 5-fluorouracil (5-FU) to increase stem cell mitotic
      activity, which peaked on day 8 post-5-FU. The infectivity titer of the vector,
      pSFF-mPrP-3F4, was determined by a novel assay in which antigen-positive foci of
      infected cells were detected after replication and spread of the vector in
      cultures of mixed packaging cell lines. Infection of Sca-1+/Lineageneg-low cells
      with pSFF-mPrP-3F4 resulted in marker protein expression in 40% of the progeny
      cells after 7 days of culture. Transplantation of marrow cells or sorted Sca
      1+/Lineageneg-low cells transduced with vector resulted in 3F4-positive mPrP
      expression in 11% to 37% of donor-derived peripheral blood leukocytes at 2 weeks.
      Though the percentage of 3F4-positive blood cells gradually declined, at 28 weeks
      23% of recipient mice still maintained expression of the marker gene. Expression
      was observed in lymphoid, myeloid, and erythroid lineages and was detected in Sca
      1+/Lineageneg-low marrow cells. The multilineage, high-frequency expression
      observed suggests that pSFF may be useful in gene therapy directed at
      hematopoietic stem cells and their differentiated progeny.

PMID- 8555473
TI  - Human osteoblasts support human hematopoietic progenitor cells in vitro bone
      marrow cultures.
AB  - Hematopoietic stem cell differentiation occurs in direct proximity to osteoblasts
      within the bone marrow cavity. Despite this striking affiliation, surprisingly
      little is known about the precise cellular and molecular impact of osteoblasts on
      the bone marrow microenvironment. Recently, we showed that human osteoblasts
      produce a variety of cytokine mRNAs including granulocyte colony-stimulating
      factor, granulocyte-macrophage colony-stimulating factor, and interleukin-6. We
      examined here the ability of osteoblasts to support the development of
      hematopoietic colonies from progenitors as well the ability to maintain long-term
      culture-initiating cells (LTC-IC) in vitro. Examination of the hematopoietic
      cells recovered after 2 weeks of culture showed that osteoblasts support the
      maintenance of immature hematopoietic phenotypes. In methylcellulose assays,
      osteoblasts stimulate the development of hematopoietic colonies to a level at
      least 10-fold over controls from progenitor cells. Using limiting dilutional bone
      marrow cultures, we observed an activity produced by osteoblasts resulting in an
      threefold to fourfold expansion of human LTC-IC and progenitor cells in vitro.
      Thus, the presence of hematopoietic stem cells in close proximity to endosteal
      surfaces in vivo may be due in part to a requirement for osteoblast-derived
      products.

PMID- 8555474
TI  - Retroviral transfer of the recombinant human erythropoietin receptor gene into
      single hematopoietic stem/progenitor cells from human cord blood increases the
      number of erythropoietin-dependent erythroid colonies.
AB  - To test whether an enforced expression of a lineage-specific cytokine receptor
      would influence the proliferation/differentiation of hematopoietic
      stem/progenitor cells, retroviral vectors containing the human erythropoietin
      receptor (hEpoR) gene were used to transduce the hEpoR gene into phenotypically
      sorted subsets of cells. CD34 , CD34++CD33-, and CD34++CD33+ populations of human
      cord blood, highly enriched for hematopoietic stem/progenitor cells, were sorted
      and plated as single cells per well in methylcellulose culture medium containing
      early acting growth factors in the presence or absence of Epo. The hEpoR gene was
      efficiently transduced into single high proliferative potential colony-forming
      cells (HPP-CFC) and multipotential (colony-forming unit granulocyte, erythroid,
      monocyte, megakaryocyte [CFU-GEMM]), erythroid (burst-forming unit-erythroid [BFU
      E]), and granulocyte-macrophage (colony-forming unit-granulocyte-macrophage [CFU
      GM]) progenitor cells. As expected in cultures grown in the absence of Epo, no
      BFU-E or CFU-GEMM colonies grew. In the presence of Epo, the hEpoR-gene
      transduced cells formed significantly more CFU-GEMM and BFU-E colonies than did
      the controls. A significant decrease in HPP-CFC colonies was also observed under
      these conditions. Little or no effect of hEpoR gene transduction was apparent in
      the numbers of CFU-GM colonies formed in the presence or absence of Epo. All of
      the above results were similar whether the cell populations assessed were CD34 or
      their CD33- or CD33+ subsets plated in the presence of growth factors at 200
      cells/mL or after limiting dilution at 2 cells/well. These results suggest that
      the profile of detectable stem/progenitors can be altered by retrovirus-mediated
      expression of the hEpoR gene.

PMID- 8555475
TI  - Human dendritic cell differentiation pathway from CD34+ hematopoietic precursor
      cells.
AB  - The most effective antigen-presenting cells for T lymphocytes are dendritic cells
      (DCs), the differentiation pathway of which, however, is incompletely
      characterized. We examined here how DCs differentiated from human cord blood
      CD34+ progenitor cells cultured with granulocyte-macrophage colony-stimulating
      factor, tumor necrosis factor-alpha, and stem cell factor. After 5 days, 2 of 3
      nonadherent cells were CD13hiHLA-DRhiCD4+, half of them were also CD14+, and < or
      = 10% were CD1a+. When day-5 sorted CD13hiCD1a- and CD13lo cells were further
      cultured, CD1a+ cells appeared in the already CD13hi population, whereas CD13hi
      cells, a minority of which rapidly became CD1a+, emerged from the CD13lo
      population. By day 12, still 66% of bulk cells in suspension were CD13hi, most of
      which displayed high forward and side scatters of large granular cells. Half of
      CD13hi cells were CD1a+. All CD13hi cells expressed to the same extent DR, CD4,
      costimulatory and adhesion molecules, and various amounts of CD14. CD1a+ cells
      stimulated allogeneic lymphocytes more than CD13hiCD1a- cells and, although they
      were CD14+, both cell types were nonspecific esterase-negative nonphagocytic
      cells and were stronger mixed leukocyte reaction stimulators than were their
      macrophage counterparts. Eventually, the percentage of CD1a+ cells decreased.
      However, typical CD1a+ DCs still emerged in culture of sorted day-12 CD13hiCD1a-
      cells, and adding interleukin-4 to bulk cultures at that time led to the
      persistence of the CD1a+ population while diminishing CD14 expression. Thus, this
      system results first in the differentiation of CD13hi precursors that strongly
      express DR and CD4, from which more mature CD1a+ DCs continuously differentiate
      all along the culture period.

PMID- 8555476
TI  - Retention of quiescent hematopoietic cells with high proliferative potential
      during ex vivo stem cell culture.
AB  - Human CD34+/Thy-1+/Lin- hematopoietic cells purified from bone marrow (BM) or
      mobilized peripheral blood (MPB) are highly enriched for pluripotent stem cells.
      Ex vivo expansion of this population is proposed as a means of providing
      accelerated short-term, as well as long-term, engraftment after myeloablative
      therapy. Here we demonstrate that primitive quiescent cells are retained in bulk
      expansion cultures of CD34+/Thy-1+/Lin- cells and that the cell production
      capacity of the expanded cell product can largely be attributed to cells
      exhibiting quiescent behavior during culture. CD34+/Thy-1+/Lin- cells from adult
      BM or MPB were labeled with the fluorescent membrane dye PKH26, followed by in
      vitro culture of 10(4) cells on a murine stromal layer in the presence of
      interleukin (IL)-3, IL-6, c-kit ligand (KL), and leukemia inhibitory factor
      (LIF). With each subsequent cell division, PKH26 fluorescence is reduced by
      roughly half, which allows tracking of the number of cell divisions. Progenitor
      cells present after a 2-week expansion period were sorted into CD34+/Lin
      /dyebright and CD34+/Lin-/dyedim fractions and then cultured in a 4-week single
      cell proliferation assay to characterize the proliferative capacity of each
      group. Fifty-nine percent of progenitors remaining dyebright after bulk culture
      (four or fewer cell divisions) were observed to proliferate in single cell
      culture, and produced an average of 1,780 cells per plated cell. In contrast,
      only 26% of dyedim (more than four divisions) progenitors were observed to
      proliferate and displayed a lower average proliferative capacity of 225 cells per
      plated cell. Similar behaviors were observed after a second consecutive cycle of
      bulk culture, indicating that quiescent cells with high proliferative capacity
      existed in culture for at least 4 weeks. Single CD34+/Lin-/dyebright progenitors
      purified from bulk cultures were observed to produce as many as 1,000 CD34
      positive progeny during single cell culture, and these progeny included
      multilineage colony forming cells. These data demonstrate that among CD34
      positive cells recovered after in vitro bulk culture, a higher proliferative
      capacity correlated with quiescent behavior. The described culture method
      provides quantitation of the cell producing capacity of individual cells in
      hematopoietic cell mixtures and may prove useful for predicting engrafting
      potential in products intended for cellular therapy.

PMID- 8555477
TI  - Development of day-8 colony-forming unit-spleen hematopoietic progenitors during
      early murine embryogenesis: spatial and temporal mapping.
AB  - The ontogeny of the hematopoietic system in mammalian embryos occurs during the
      yolk sac (YS) and the fetal liver (FL) stages. Events leading to the
      establishment of hematopoiesis in the FL remain obscure. The appearance of colony
      forming units-spleen (CFU-S) in the FL is preceded by a gradual increase of CFU-S
      in the YS and a more rapid increase in the AGM region (area comprising dorsal
      aorta, gonads, and mesonephros) during day 10 of development (Medvinsky et al,
      Nature 364:64, 1993). By this time, the AGM CFU-S attain a high frequency
      equivalent to that found in the adult bone marrow. The analogous area gives rise
      to adult hematopoiesis in amphibians and probably in birds. We present here a
      more complete picture of CFU-S development during transition from the pre-liver
      to liver stage of hematopoiesis. (1) Dissectional analysis of the mouse AGM
      region shows the presence of CFU-S both around the dorsal aorta and in the uro
      genital ridges. (2) The embryonic gut also shows low but distinctive CFU-S
      activity. This initial intrabody pattern of CFU-S distribution in murine
      embryogenesis parallels that found for primordial germ cells. (3) The beginning
      of definitive liver hematopoiesis is accompanied by wide dissemination of CFU-S
      in the embryonic tissues. (4) Comparison of spleen colonies arising from the AGM
      and YS has shown morphologic differences. In contrast to simple erythroid
      constitution of the YS colonies, a broader variety of cells are found within the
      AGM-derived colonies that are similar to those derived from 11-day FL. These data
      suggest a lineage relationship for hematopoietic progenitors between the AGM
      region and the FL.

PMID- 8555478
TI  - Thrombopoietin in thrombocytopenic mice: evidence against regulation at the mRNA
      level and for a direct regulatory role of platelets.
AB  - Thrombopoietin (TPO), originally described as an activity in the serum of
      thrombocytopenic animals that leads to increased production of platelets, has
      recently been isolated and cloned. Its closest relative in the cytokine
      superfamily, erythropoietin (EPO), is transcriptionally regulated during anemia,
      and it was expected that TPO would similarly be regulated during
      thrombocytopenia. We induced thrombocytopenia in mice and confirmed that TPO
      activity was upregulated, as determined by a bioassay. Liver and kidney were
      found to be the major sources of TPO mRNA. Surprisingly, TPO mRNA in these
      tissues was not upregulated in thrombocytopenic mice. Using a sensitive RNase
      protection assay that can distinguish between TPO isoforms, we found no change in
      the profile of mRNA for these isoforms. A semiquantitative reverse transcription
      polymerase chain reaction assay also did not demonstrate upregulation of TPO mRNA
      in the spleen. Thus, the increase of TPO activity during thrombocytopenia is not
      caused by regulation at the level of TPO mRNA. Furthermore, isolated mouse
      platelets absorbed high amounts of bioactive TPO out of TPO-conditioned medium in
      a dose-dependent fashion. Our results are consistent with TPO protein being
      regulated at a posttranscriptional level and/or directly through absorption and
      metabolism by platelets.

PMID- 8555479
TI  - CD14+ cells in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral
      blood mononuclear cells induce secretion of interleukin-6 and G-CSF by marrow
      stroma.
AB  - The ability of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral
      blood mononuclear cells (G-PBMCs) to induce secretion of cytokines in primary
      long-term marrow cultures (LTC) or in the human marrow stromal cell line HS23 was
      compared with that of marrow mononuclear cells. Equal numbers of G-PBMCs or
      marrow mononuclear cells were added to stromal cultures, supernatants were
      harvested at day 4 and levels of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL
      2, IL-6, G-CSF, and tumor necrosis factor alpha (TNF alpha) were determined. G
      PBMCs induced 21.4-fold higher levels of IL-6 and 12.5-fold higher levels of G
      CSF in LTC cocultures compared with marrow mononuclear cells and induced 20.6
      fold more IL-6 and 6.3-fold more G-CSF when added to HS23 cells. Experiments
      using sorted populations of CD20+, CD3+, and CD14+ cells showed that CD14+ cells
      within G-PBMCs were responsible for triggering the production of IL-6 and G-CSF.
      The effect did not require cell-cell contact and was inhibited when neutralizing
      antibodies to IL-1 alpha and IL-1 beta were used in combination. In these
      experiments, the greater stimulating ability of G-PBMCs is most likely
      attributable to the greater number of CD14+ cells in G-PBMCs (26.1+% +/- 2.3%)
      compared with marrow (2.5% +/- 0.8%), because equal numbers of CD14+ cells sorted
      from marrow and G-PBMCs showed comparable ability to induce IL-6 and G-CSF when
      placed directly on stromal cells.

PMID- 8555480
TI  - Acceleration of hematopoietic reconstitution with a synthetic cytokine (SC-55494)
      after radiation-induced bone marrow aplasia.
AB  - The synthetic cytokine (Synthokine) SC-55494 is a high-affinity interleukin-3 (IL
      3) receptor ligand that stimulates greater in vitro multilineage hematopoietic
      activity than native IL-3, while inducing no significant increase in inflammatory
      activity relative to native IL-3. The aim of this study was to investigate the in
      vivo hematopoietic response of rhesus monkeys receiving Synthokine after
      radiation-induced marrow aplasia. Administration schedule and dose of Synthokine
      were evaluated. All animals were total-body irradiated (TBI) with 700 cGy 60Co
      gamma radiation on day 0. Beginning on day 1, cohorts of animals (n = 5) received
      Synthokine subcutaneously (SC) twice daily with 25 micrograms/kg/d or 100
      micrograms/kg/d for 23 days or 100 micrograms/kg/d for 14 days. Control animals
      (n = 9) received human serum albumin SC once daily at 15 micrograms/kg/d for 23
      days. Complete blood counts were monitored for 60 days postirradiation and the
      durations of neutropenia (NEUT; absolute neutrophil count [ANC] < 500/microL) and
      thrombocytopenia (THROM; platelet count < 20,000/microL) were assessed.
      Synthokine significantly (P < .05) reduced the duration of THROM versus the HSA
      treated animals regardless of dose or protocol length. The most striking
      reduction was obtained in the animals receiving 100 micrograms/kg/d for 23 days
      (THROM = 3.5 v 12.5 days in HSA control animals). Although the duration of NEUT
      was not significantly altered, the depth of the nadir was significantly lessened
      in all animal cohorts treated with Synthokine regardless of dose versus schedule
      length. Bone marrow progenitor cell cultures indicated a beneficial effect of
      Synthokine on the recovery of granulocyte-macrophage colony-forming units that
      was significantly higher at day 24 post-TBI in both cohorts treated at 25 and 100
      micrograms/kg/d for 23 days relative to the control animals. Plasma
      pharmacokinetic parameters were evaluated in both normal and irradiated animals.
      Pharmacokinetic analysis performed in irradiated animals after 1 week of
      treatment suggests an effect of repetitive Synthokine schedule and/or TBI on
      distribution and/or elimination of Synthokine. These data show that the
      Synthokine, SC55 94, administered therapeutically post-TBI, significantly
      enhanced platelet recovery and modulated neutrophil nadir and may be clinically
      useful in the treatment of the myeloablated host.

PMID- 8555481
TI  - Sequence 274-368 in the beta 3-subunit of the integrin alpha IIb beta 3 provides
      a ligand recognition and binding domain for the gamma-chain of fibrinogen that is
      independent of platelet activation.
AB  - Several bacterial-expressed recombinant fragments encompassing the extracellular
      part of the beta 3 subunit of the integrin alpha IIb beta 3 were shown to
      recognize and bind soluble and immobilized forms of fibrinogen. Two of them,
      designated as rIII-11 (beta 3 274-368) and rIII-13 (beta 3 274-403), did not
      contain the established RGD-ligand binding sequence. In fact, they interacted, in
      a Ca(2+)-independent manner, with the C-terminal part of the fibrinogen gamma
      chain. Both beta 3 fragments blocked the participation of fibrinogen in the
      induction of platelet aggregation induced by adenosine diphosphate. Fragment rIII
      13 was recognized by the anti-beta 3 monoclonal antibody B2A. This antibody,
      which possesses an epitope exposed on both resting and activated platelets,
      inhibited fibrinogen binding as well as platelet adhesion and aggregation. In
      conclusion, the results demonstrated that the 274-368 sequence of the beta 3
      subunit of integrin alpha IIb beta 3 constitutes a fibrinogen ligand binding
      domain, distinct from the RGD-binding site, that is required for both platelet
      adhesion and aggregation.

PMID- 8555482
TI  - Internalization of bound fibrinogen modulates platelet aggregation.
AB  - In agonist-stimulated platelets, the integrin alpha IIb beta 3 (glycoprotein IIb
      IIIa) is converted from an inactive to an active fibrinogen receptor, thereby
      mediating platelet aggregation. With time after agonist addition, at least two
      events occur: fibrinogen becomes irreversibly bound to the platelet and, when
      stirring is delayed, platelets lose the ability to aggregate despite the presence
      of maximally bound fibrinogen. Because we previously identified an actively
      internalized pool of alpha IIb, beta 3 in platelets, we explored the possibility
      that both of these events might result from the internalization of fibrinogen
      bound to active alpha IIb beta 3. Under conditions of irreversible fibrinogen
      binding, fluorescence microscopy showed that biotinylated fibrinogen is rapidly
      internalized by activated platelets to a surface-inaccessible, intracellular
      pool. Flow cytometric analysis showed that the observed loss in accessibility to
      extracellular probes immediately precedes a loss in ability to the platelets to
      aggregate. Moreover, prevention of irreversible fibrinogen binding results in a
      prevention of internalization and a retention of aggregation capacity. Thus, the
      internalization of fibrinogen from the activated platelet surface appears to
      contribute not only to the irreversible phase of fibrinogen binding, but also to
      the downregulation of platelet adhesiveness. Fibrinogen internalization is
      therefore likely to represent a fundamental regulatory mechanism that modulates
      platelet function.

PMID- 8555483
TI  - All-trans-retinoic acid counteracts endothelial cell procoagulant activity
      induced by a human promyelocytic leukemia-derived cell line (NB4).
AB  - Therapy with all-trans-retinoic acid (ATRA) can rapidly improve the coagulopathy
      of acute promyelocytic leukemia (APL). This study was designed to evaluate
      whether the APL cell line NB4 induces the procoagulant activity (PCA) of human
      endothelial cells (ECs) in vitro, and whether this property is modified after
      ATRA-induced NB4 maturation. EC monolayers were incubated for 4 hours at 37
      degrees C with the conditioned media (CM) of NB4 treated with 1 mumol/L ATRA
      (ATRA-NB4-CM) or the vehicle (control-NB4-CM). EC lysates were tested for PCA.
      ATRA-NB4-CM induced significantly more PCA:tissue factor (TF) than control-NB4-CM
      (P < .01). To identify the cause of TF induction, interleukin (IL)-1 beta antigen
      levels were measured in CM samples. ATRA-NB4-CM contained significantly more IL-1
      beta than control-NB4-CM. EC PCA was significantly inhibited by an anti-IL-1 beta
      antibody. The addition to the media of 10 mumol/L ATRA counteracted the EC TF
      expression induced by NB4-CM. These data indicate that ATRA increases the
      promyelocyte-induced EC TF, partly through increased IL-1 beta production.
      However, ATRA can protect the endothelium from the procoagulant stimulus of
      leukemic cells.

PMID- 8555484
TI  - Thrombin-induced GPIb-IX centralization on the platelet surface requires actin
      assembly and myosin II activation.
AB  - In resting platelets, the GPIb-IX complex, the receptor for the von Willebrand
      factor (vWF), is linked to underlying actin filaments by actin-binding protein
      (ABP-280). Thrombin stimulation of human platelets leads to a decrease in the
      surface expression of the GPIb-IX complex, which is redistributed from the
      platelet surface into the open canalicular system (OCS). Because the
      centralization of GPIb-IX is inhibited by cytochalasin, it is believed to be
      linked to actin cytoskeletal rearrangements that take place during platelet
      activation. We have further characterized the mechanism of GPIb-IX centralization
      in platelets in suspension. Following thrombin stimulation, GPIb-IX shifts from
      the membrane skeleton of the resting cell to the cytoskeleton of the activated
      cell in a reaction sensitive to cytochalasin B. The cytoskeletal association of
      GPIb-IX involves ABP-280, as it correlates with the incorporation of ABP-280 into
      the activated cytoskeleton and because no dissociation of the ABP-280/GPIb-IX
      complexes is detected after thrombin activation. However, the incorporation of
      GPIb-IX into the cytoskeleton is complete within 1 minute, whereas GPIb-IX
      centralization requires 5 to 10 minutes for completion. The movement of GPIb-IX
      to the cytoskeleton of activated platelets is therefore necessary, but not
      sufficient for GPIb-IX centralization. Blockage of cytosolic calcium increases
      induced by thrombin by loading with the cell permeant calcium chelator Quin-2 AM
      inhibited GPIb-IX centralization by 70%, but did not prevent its association with
      the activated cytoskeleton. Quin-2 loading did, however, decrease the
      incorporation of myosin II into the activated cytoskeleton. The role of myosin II
      was further probed using the myosin light chain kinase (MLCK) inhibitor
      wortmannin. Wortmannin prevents myosin II association to the activated
      cytoskeleton and inhibits GPIb-IX centralization by 50%, without affecting actin
      assembly or the association of GPIb-IX to the cytoskeleton. Only micromolar
      concentrations of wortmannin, high enough to inhibit MLCK, prevent GPIb-IX
      centralization. These results indicate that thrombin-induced GPIb-IX
      centralization requires a minimum of two steps, one associating GPIb-IX to the
      activated cytoskeleton and the second requiring myosin II activation. The
      involvement of myosin II implies that GPIb-IX/ABP-280 complexes, linked to actin
      filaments, are pulled into the cell center, and that platelets may exert
      contractile tension on vWF bound to its receptor.

PMID- 8555485
TI  - Molecular cloning and expression of murine vascular endothelial-cadherin in early
      stage development of cardiovascular system.
AB  - An early step in the formation of the extraembryonic and intraembryonic
      vasculature is endothelial cell differentiation and organization in blood islands
      and vascular structures. This involves the expression and function of specific
      adhesive molecules at cell-to-cell junctions. Previous work showed that
      endothelial cells express a cell-specific cadherin (vascular endothelial [VE]
      cadherin, or 7B4/cadherin-5) that is organized at cell-to-cell contacts in
      cultured cells and is able to promote intercellular adhesion. In this study, we
      investigated whether VE-cadherin could be involved in early cardiovascular
      development in the mouse embryo. We first cloned and sequenced the mouse VE
      cadherin cDNA. At the protein level, murine VE-cadherin presented 75% identity
      (90%, considering conservative amino acid substitutions) with the human
      homologue. Transfection of murine VE-cadherin cDNA in L cells induced Ca(++)
      dependent cell-to-cell aggregation and reduced cell detachment from monolayers.
      In situ hybridization of adult tissues showed that the murine molecule is
      specifically expressed by endothelial cells. In mouse embryos, VE-cadherin
      transcripts were detected at the very earliest stages of vascular development
      (E7.5) in mesodermal cells of the yolk sac mesenchyme. At E9.5, expression of VE
      cadherin was restricted to the peripheral cell layer of blood islands that gives
      rise to endothelial cells. Hematopoietic cells in the center of blood islands
      were not labeled. At later embryonic stages, VE-cadherin transcripts were
      detected in vascular structures of all organs examined, eg, in the ventricle of
      the heart, the inner cell lining of the atrium and the dorsal aorta, in
      intersomitic vessels, and in the capillaries of the developing brain. A
      comparison with flk-1 expression during brain angiogenesis revealed that brain
      capillaries expressed relatively low amounts of VE-cadherin. In the adult brain,
      the level of VE-cadherin transcript was further reduced. By immunohistochemistry,
      murine VE-cadherin protein was detected at cell-to-cell junctions of endothelial
      cells. Overall, these data demonstrate that VE-cadherin is an early,
      constitutive, and specific marker of endothelial cells. This distinguishes this
      molecule from other cadherins and suggests that its expression is associated with
      the early assembly of vascular structures.

PMID- 8555486
TI  - Activated protein C attenuates endotoxin-induced pulmonary vascular injury by
      inhibiting activated leukocytes in rats.
AB  - We investigated the effect of activated protein C (APC) on lipopolysaccharide
      (LPS)-induced pulmonary vascular injury in rats to investigate the possible
      usefulness of APC as a treatment for adult respiratory distress syndrome.
      Intravenously administered LPS (5 mg/kg) significantly increased pulmonary
      vascular permeability. APC prevented the LPS-induced increase in pulmonary
      vascular permeability observed at 6 hours. Heparin plus antithrombin III (ATIII)
      and active site-blocked factor Xa (DEGR-Xa), a selective inhibitor of thrombin
      generation, inhibited LPS-induced coagulopathy but did not prevent LPS-induced
      pulmonary vascular injury. LPS-induced pulmonary vascular injury was
      significantly attenuated in rats with nitrogen mustard-induced leukocytopenia and
      in rats treated with ONO-5046, a potent granulocyte elastase inhibitor.
      Administration of LPS also increased pulmonary accumulation of leukocytes, as
      evaluated by measurement of myeloperoxidase activity in the lungs. APC
      significantly reduced LPS-induced increases in pulmonary accumulation of
      leukocytes at 1 hour. Neither ATIII plus heparin nor DEGR-Xa inhibited leukocyte
      accumulation. Active site-blocked APC (DIP-APC) prevented neither the LPS-induced
      pulmonary accumulation of leukocytes nor the LPS-induced increase in pulmonary
      vascular permeability. These results suggest that the mechanism of APC inhibition
      of LPS-induced pulmonary vascular injury was independent of its anticoagulant
      activity and was related to its ability to inhibit accumulation of leukocytes. In
      addition, these findings suggest that the serine protease activity of APC may be
      essential to its inhibitory effect on LPS-induced pulmonary accumulation of
      leukocytes and subsequent pulmonary vascular injury.

PMID- 8555487
TI  - Thrombin receptors activate potassium and chloride channels.
AB  - We used DAMI human megakaryocytic leukemia cells to study transmembrane ion
      currents activated through the G-protein-coupled thrombin receptor pathway. When
      the cells were stimulated by thrombin receptor-activating peptide, an increase in
      cytosolic Ca2+ ([Ca2+]i) developed as predicted by the known effect that thrombin
      exerts in the platelet. We then monitored the membrane potentials of individual
      DAMI cells during this response and observed complex, triphasic changes that
      could not be accounted for by Ca2+ fluxes alone. These consisted of rapid
      hyperpolarization, followed by depolarization to values more positive than the
      resting potential and then by slow repolarization. For the purpose of this study,
      we focused on the hyperpolarizing current that developed immediately after
      thrombin receptor activation. This proved to be composed of (1) a Ca(2+)
      independent, outwardly rectifying Cl- current and (2) a strongly hyperpolarizing,
      inwardly rectifying, Ba(2+)-sensitive K+ current that required an increase of
      [Ca2+]i for activation. By analogy with their functions in other cell systems, it
      is logical to conclude that these prominent K+ and Cl- conductances may serve to
      regulate the complex volume changes that accompany thrombin receptor activation
      and/or to increase the electromotive drive that supports Ca2+ influx under these
      conditions through hyperpolarization of the cell membrane.

PMID- 8555488
TI  - Anticoagulant effects of retinoic acids on leukemia cells.
AB  - We have recently found that all-trans retinoic acid (ATRA) upregulates
      thrombomodulin (TM) and downregulates tissue factor (TF) expression in acute
      myelogenous leukemia (AML) M3 cells (NB4) and acute monoblastic leukemia cells
      (U937) (Koyama et al, Blood 84:3001, 1994). We have further investigated the
      effects of ATRA on leukemic cells freshly isolated from patients at diagnosis.
      Increase of TM antigen was documented in all AML cells: M0 (n = 1), M2 (n = 5),
      M3 (n = 3), M4 (n = 3), M5 (n = 3), and M6 (n = 1). Decrease of TF antigen was
      observed in 4 M2, 1 M4, and all M3 and M5 patients. However, no TM and TF
      antigens were detected in all chronic lymphocytic leukemia cells (n = 3) with or
      without ATRA treatment. Changes of TM and TF antigen levels were associated with
      those of TM and TF cofactor levels on the cell surface. A stereoisomer of RA, 9
      cis RA, is a high-affinity ligand for the RA receptors (RARs) and the retinoid X
      receptors, although ATRA and another isomer, 13-cis RA, solely bind to RARs. We
      have also studied the effects of 9-cis RA and 13-cis RA on the expressions of TM
      and TF in NB4 and U937 cells. A relatively wide range of 9-cis RA concentrations
      (0.01 to 1 mumol/L) compared with ATRA was optimal for prolongation of normal
      plasma-based recalcification time (reduction of cell surface TF activity),
      decrease of TF antigen, and increase of TM antigen on the surface and in the
      lysates of NB4 and U937 cells. Western blot analysis under nonreducing conditions
      showed that both ATRA and 9-cis RA markedly induced the prominent band at 75 kD
      of TM and reduced the band at 45 kD of TF. Northern blot analysis has shown
      similar changes of mRNA levels, which indicates that RAs regulate TM and TF
      expression in leukemic cells at transcriptional levels. Anticoagulant effects of
      ATRA, ie, upregulation of TM expression and downregulation of TF expression, are
      applied not only to established cell lines of specific subtypes (M3 and M5) but
      also to more universal AML (most cases of M3 and M5 and a part of the other types
      of AML) cells freshly isolated from patients. 9-cis RA may be more effective than
      ATRA as an inducer of differentiation of AML M3 cells and as an anticoagulant
      agent for patients with certain types of AML as well.

PMID- 8555489
TI  - The promoter and 5' flanking sequences controlling human B29 gene expression.
AB  - The product of the B-cell-specific B29 gene (B29, Ig beta, CD79b) is essential
      for Ig-mediated B-cell activation via the B-cell antigen receptor complex (BCR)
      on human and murine B lymphocytes. To better understand the regulation of this
      pivotal gene, we have analyzed the human genomic DNA sequence upstream of the B29
      ATG start codon for transcriptional control activity. The human B29 gene lacks
      either a TATA or a CAAT box and transcription is initiated at multiple sites. The
      minimal promoter of the human B29 gene is contained within a 193-bp region 5' of
      these multiple start sites. This minimal promoter exhibits B-cell-specific
      activity and contains SP1, ETS, OCT, and IKAROS/LYF-1 transcription factor
      motifs. All these motifs are strikingly conserved in sequence and placement
      relative to the previously characterized murine B29 promoter. Additional upstream
      gene segments dramatically affected B29 minimal promoter activity. A newly
      identified motif called the B29 conserved sequence (BCS), found upstream of both
      human and murine B29 promoters, appears to stimulate B29 transcription through a
      novel mechanism. A single BCS had little effect either on the minimal B29
      promoter or on a heterologous promoter. Instead, the BCS stimulated transcription
      by counteracting 5' negative regulatory DNA sequences that block the activity of
      the B29 minimal promoter in its absence. These findings indicate that B29 gene
      expression is controlled by the complex interplay of positive and negative
      regulatory elements.

PMID- 8555490
TI  - Persistent activation of the tumor necrosis factor system in a subgroup of
      patients with common variable immunodeficiency--possible immunologic and clinical
      consequences.
AB  - In patients with common variable immunodeficiency (CVI), we have previously
      defined a subgroup of patients (CVIHyper) characterized by decreased numbers of
      CD4+ lymphocytes in peripheral blood, splenomegaly, and persistent immune
      activation in vivo, particularly of monocytes/macrophages. To further
      characterize this hyperactivity, parameters of activation of the tumor necrosis
      factor (TNF) system (TNF alpha and soluble TNF receptors [sTNFRs]) were measured
      in 24 patients with CVI and 20 healthy controls. Patients with CVI had
      significantly higher serum levels of TNF alpha and both types of sTNFRs, with the
      highest levels in the CVIHyper subgroup. In vitro, peripheral blood mononuclear
      cells (PBMC) and purified monocytes from CVIHyper patients spontaneously released
      significantly higher levels, and, after lipopolysaccharide (LPS) stimulation,
      significantly lower levels of TNF alpha and soluble p75-TNFR than cells from both
      other CVI patients and healthy controls. CVIHyper patients also had significantly
      higher TNF alpha:sTNFRs ratios in both serum and in unstimulated PMBC
      supernatants. The present study demonstrates persistent in vivo activation of the
      TNF system in CVI, particularly in the CVIHyper subgroup. This activation may
      contribute to the pathogenesis of both clinical and immunologic manifestations in
      CVI.

PMID- 8555491
TI  - An ATP-activated channel is involved in mitogenic stimulation of human T
      lymphocytes.
AB  - We investigated the effect of pharmacologic modulation of the ATP receptor on
      intracellular ion changes and proliferative response of human peripheral blood
      lymphocytes (PBLs) and purified T lymphocytes. Extracellular ATP (ATPe) triggered
      in these cells an increase in the cytoplasmic Ca2+ concentration ([Ca2+]i) and
      plasma membrane depolarization. Whereas both Ca2+ release from intracellular
      stores and influx across the plasma membrane were detected in the whole PBL
      population, only Ca2+ influx was observed in T cells. In the presence of near
      physiologic extracellular Na+ concentrations (125 mmol/L), Ca2+ permeability
      through the ATPe-gated channel was very low, suggesting a higher selectivity for
      monovalent over divalent cations. The selective P2Z agonist benzoylbenzoic ATP
      (BzATP) increased [Ca2+]i in the presence but not the absence of extracellular
      Ca2+ and also caused plasma membrane depolarization. The covalent blocker
      oxidized ATP (oATP), an inhibitor of P2X and P2Z receptors, prevented Ca2+ influx
      and plasma membrane depolarization, but had no effect on Ca2+ release from
      stores. Stimulation with ATPe alone had no significant effects on PBL 3H
      thymidine incorporation. On the contrary, ATPe or BzATP had a synergistic effect
      on DNA synthesis stimulated by selective T-cell mitogens such as
      phytohemagglutinin, anti-CD3 monoclonal antibody, or allogenic PBLs (mixed
      lymphocyte cultures). Treatment with oATP inhibited mitogenic stimulation by
      these receptor-directed agents but not by the combined application of the Ca2+
      ionophore ionomycin and phorbol myristate acetate. Interleukin-2 partially
      relieved inhibition by oATP. These results suggest that human T lymphocytes
      express a plasma membrane channel gated by ATPe that is involved in mitogenic
      stimulation.

PMID- 8555492
TI  - Interleukin-4 gene expression in activated human T lymphocytes is regulated by
      the cyclic adenosine monophosphate-dependent signaling pathway.
AB  - In the present study, we have investigated the involvement of the cyclic
      adenosine monophosphate (cAMP)-dependent signaling pathway on interleukin-4 (IL
      4) gene expression in freshly isolated human T lymphocytes. 2'-0-dibutyryl cAMP
      (db-cAMP) and prostaglandin E2 (PGE2) were used to directly and indirectly
      activate the protein kinase A pathway. Northern analysis showed that concanavalin
      A (Con A)-, anti-CD3 (alpha CD3)-, or anti-CD3 plus anti-CD28 (alpha CD3/alpha
      CD28)-induced accumulation of IL-4 mRNA was inhibited by db-cAMP (10(-3) mol/L).
      Db-cAMP showed a steep dose-dependent inhibition; concentrations < or = 10(-4)
      mol/L did not affect IL-4 mRNA accumulation. In contrast, GM-CSF mRNA expression
      showed a wider dose-dependent range; 10(-5) mol/L db-cAMP still affected GM-CSF
      accumulation. PGE2 inhibited the Con A- and alpha CD3/alpha CD28-induced
      accumulation of IL-4 mRNA in a dose-dependent fashion. Con A-induced IL-4 mRNA
      was inhibited by 10(-4) to 10(-7) mol/L PGE2; alpha CD3/alpha CD28-induced IL-4
      mRNA was inhibited by 10(-5) to 10(-8) mol/L PGE2. Nuclear run-on experiments
      showed that the inhibitory effects of db-cAMP and PGE2 were accomplished at
      transcriptional level in Con A-activated T cells, whereas changes at
      transcriptional and posttranscriptional level were involved in alpha CD3/alpha
      CD28-activated T lymphocytes. In contrast to Con A and alpha CD3/alpha CD28
      activation, phorbol myristate acetate plus A23187-induced IL-4 mRNA expression
      was insensitive to the inhibitory effect of db-cAMP and PGE2. Moreover, it
      appeared that the sensitivity for cAMP-mediated downregulation could not be
      blocked by stimulation T lymphocytes with alpha CD3/alpha CD28 in the presence of
      IL-2, IL-7, IL-10, IL-12, or a combination of these cytokines. Finally, it was
      shown that, in accordance with the mRNA studies, db-cAMP and PGE2 suppressed the
      IL-4 secretion in Con A- and alpha CD3/alpha CD28-activated T cells. In
      conclusion, these data show that IL-4 expression is negatively regulated by the
      protein kinase A-dependent signaling pathway by transcriptional and
      posttranscriptional mechanisms that depend on costimulatory signals.

PMID- 8555493
TI  - Pharmacokinetics and immunomodulatory properties of intravenously administered
      recombinant human interleukin-10 in healthy volunteers.
AB  - Normal volunteers received single doses of recombinant human interleukin-10 (rhIL
      10; n = 6 per group) or placebo (n = 3 per group) by intravenous injection to
      characterize pharmacokinetics, tolerability, and immunomodulatory effects.
      Dosages were 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 25.0, 50.0, and 100.0 micrograms/kg.
      Dose-related adverse effects consisted of a mild-to-moderate flu-like syndrome
      characterized by fever with chills, headache, and myalgias at the highest dose.
      The mean terminal phase t1/2 ranged from 2.3 +/- 0.5 to 3.7 +/- 0.8 hours. Dose
      related effects of rhIL-10 included transient increases of circulating
      neutrophils and monocytes and decreases of lymphocytes. rhIL-10 markedly
      suppressed, in a time- and dose-dependent manner, the synthesis of the
      inflammatory cytokines IL-1 beta and tumor necrosis factor alpha by whole blood
      stimulated ex vivo with bacterial lipopolysaccharide. Circulating numbers of
      CD14+/HLA-DR+ cells at 24 hours after the dose were increased in a dose-dependent
      manner. Effects on expression of HLA-DR by CD14+ cells were variable. There was
      no apparent effect on HLA-DR expression by CD20+ cells. The immunomodulatory
      effects of rhIL-10 merit further clinical investigation.

PMID- 8555494
TI  - BCL-2 but not its Epstein-Barr virus-encoded homologue, BHRF1, is commonly
      expressed in posttransplantation lymphoproliferative disorders.
AB  - Posttransplantation lymphoproliferative disease (PTLD) is virtually always
      associated with Epstein-Barr virus (EBV) infection. BCL-2 and other proteins that
      confer resistance to apoptosis have been implicated in the pathogenesis of a
      variety of malignancies including lymphomas. One EBV protein, BHRF1, is a
      homologue of BCL-2, whereas another, the latency membrane protein 1 (LMP-1),
      upregulates BCL-2 expression in vitro. In the present study, we used
      immunohistochemistry to study the expression of these viral and cellular proteins
      as well as a variety of other EBV-encoded proteins in PTLD. BHRF1 was not
      detected in any PTLD specimen, whereas BCL-2 was shown in 12 of 17 lesions
      examined. With one exception, all LMP1-positive cases also expressed BCL-2 and
      the absence of LMP1 was always associated with a lack of BCL-2 expression. The
      results do not support a role for the EBV homologue of BCL-2 in PTLD, but they do
      support a role for viral induction of BCL-2 expression.

PMID- 8555495
TI  - Serum neural cell adhesion molecule differentiates multiple myeloma from
      paraproteinemias due to other causes.
AB  - Serum neural cell adhesion molecule (NCAM) has been described as a prognostic
      marker in multiple myeloma (MM). Both C-reactive protein (CRP) and beta 2
      microglobulin (beta 2M) are established prognostic markers in MM. We tested the
      diagnostic value of these markers in 212 serum samples of patients with
      paraproteinemia registered prospectively in a population-based registry. Sixty
      patients had MM and 152 had other monoclonal gammopathies (hematologic diseases
      [48], paraneoplastic disease [35], autoimmune disease [15], and monoclonal
      gammopathy of undetermined significance [56]). CRP and beta 2M had wide and
      overlapping ranges in all diagnostic categories. However, serum neural cell
      adhesion molecule (NCAM) was low (< 20 U/mL) in all but 4 of 152 nonmyeloma cases
      and high (> or = 20 U/mL) in 31 (52%) of the 60 MM cases. Two patients with non
      Hodgkin's lymphoma, 1 with chronic lymphatic leukemia, and 1 with autoimmune
      disease had serum NCAM values between 20 and 30 U/mL. In a discriminant analysis
      in which serum NCAM, CRP, beta 2M, paraprotein type and concentration,
      hemoglobin, leukocyte and thrombocyte counts, creatinine, corrected calcium,
      lactate dehydrogenase, and alkaline phosphatase were included, paraprotein type
      and concentration and serum NCAM turned out to be the best combination of
      parameters predicting whether a patient had MM, with 89% of cases being correctly
      classified. Even without bone marrow and x-ray examinations, serum NCAM, in
      combination with paraprotein type and concentration, can differentiate between MM
      and nonmyeloma patients.

PMID- 8555496
TI  - B-chronic lymphocytic leukemias can undergo isotype switching in vivo and can be
      induced to differentiate and switch in vitro.
AB  - B-chronic lymphocytic leukemias (B-CLL) represent expanded clones of resting B
      lymphocytes that mostly express surface IgM (sIgM). The present study shows that
      B-CLL cells, freshly isolated from two patients, were sIgM+, sIgG-, and sIgA- but
      expressed IgG and IgA transcripts. cDNA cloning and sequencing showed that the
      VDJ segments associated to gamma and alpha heavy chain transcripts are identical
      to those from mu transcripts, thus showing that B lymphocytes giving rise to CLL
      cells have undergone isotype switching in vivo. Stimulation of these B-CLL cells
      through surface CD40 in the presence of interleukin-10 induced them to secrete
      IgG and IgA, proving that they can also differentiate into Ig-secreting cells.
      Finally, CD40-stimulated B-CLL cells were induced to switch towards IgE in
      response to interleukin-4, as shown by the presence of specific VDJ-C epsilon
      transcripts and the secretion of IgE. Therefore, B-CLL cells tested herein can
      undergo isotype switching in vivo and can be induced to undergo further isotype
      switching and differentiation in vitro.

PMID- 8555498
TI  - LAF-4 encodes a lymphoid nuclear protein with transactivation potential that is
      homologous to AF-4, the gene fused to MLL in t(4;11) leukemias.
AB  - A novel human gene, LAF-4, was isolated from a subtracted cDNA library that
      showed strong sequence similarity to AF-4, a gene that is translocated in
      t(4;11)(q21;q23) acute lymphoblastic leukemias (ALLs). In t(4;11) ALL, the AF-4
      gene at 4q21 is translocated into the MLL locus at 11q23, resulting in the
      expression of an MLL/AF-4 fusion protein that is the presumptive oncoprotein. AF
      4 and LAF-4 are homologous throughout their coding regions, yet neither protein
      is related to previously cloned genes. Human LAF-4 readily hybridized with genes
      in mouse and chicken, thus showing that this gene family has been highly
      conserved during vertebrate evolution. In mouse tissues, LAF-4 mRNA was found to
      be present at highest levels in lymphoid tissues, present at lower levels in
      brain and lung, and absent from other tissues. In human and mouse lymphoid cell
      lines, LAF-4 expression was highest in pre-B cells, intermediate in mature B
      cells, and absent in plasma cells, thus pointing to a potential regulatory role
      for LAF-4 in lymphoid development. Antibodies to LAF-4 showed it to be a nuclear
      protein that showed an uneven, granular immunofluorescence pattern. In vitro
      translated LAF-4 was able to bind strongly to double-stranded DNA cellulose.
      Furthermore, both LAF-4 and AF-4 had domains that activated transcription
      strongly when fused to the GAL4 DNA-binding domain. Interestingly, the AF-4
      transactivation domain is retained in the MLL/AF-4 fusion protein; thus, it may
      contribute to the transforming potential of the oncoprotein. Therefore, the
      cloning of LAF-4 has defined a new family of potential regulatory proteins that
      may function in lymphoid development and oncogenesis.

PMID- 8555497
TI  - Mechanisms of retinoid resistance in leukemic cells: possible role of cytochrome
      P450 and P-glycoprotein.
AB  - Retinoic acid (RA) regulates the differentiation and proliferation of a wide
      variety of different cell types and all-trans RA induces complete remission in a
      high proportion of patients with acute promyelocytic leukemia (APL). However,
      clinical resistance to retinoids may develop and poses a serious problem for
      differentiation-inducing therapy. We studied the effects of RA in combination
      with a cytochrome P450 inhibitor (clotrimazole) and a P-glycoprotein antagonist
      (verapamil) on cell growth and differentiation of RA-resistant HL-60 cells and
      fresh RA-resistant leukemic cells from two APL patients. RA-resistant HL-60 cells
      and APL cells differentiated to mature granulocytes when cultured with all-trans
      RA and either clotrimazole and verapamil but not with either of the agents alone.
      These findings were confirmed in these cells by their increased expression of
      CD11b antigen and migration-inhibitory factor-related protein-8/14 mRNAs and
      decreased levels of c-myc mRNA. These combinations also markedly decreased the
      number of viable cells and inhibited cellular proliferation. After isolation of
      microsomes, measurements showed that levels of cytochrome P450 activities in both
      wild-type and RA-resistant HL-60 cells were almost comparable. Moreover,
      expression of the CYP1A1-type cytochrome P450 gene could not be detected in
      either cell type. However, RA-resistant HL-60 cells and APL cells, but not RA
      sensitive HL-60 cells and APL cells, expressed multidrug-resistance-1 gene
      transcripts. Taken together, acquired resistance to RA may be explained in part
      by drug metabolism in leukemic cells. Possible mechanisms for accelerated
      clearance of RA include the induction of non-CYP1A1 cytochrome P450 enzymes and P
      glycoprotein.

PMID- 8555499
TI  - Ig VH gene mutational patterns indicate different tumor cell status in human
      myeloma and monoclonal gammopathy of undetermined significance.
AB  - Plasma cell tumors display a wide spectrum of clinical progression, ranging from
      aggressive multiple myeloma to a benign form known as monoclonal gammopathy of
      undetermined significance (MGUS), which requires no treatment. Because both
      diseases involve mature Ig-secreting plasma cells, the reason for this variation
      in malignant behavior is unclear. However, assessment of malignant potential is
      desirable for choice of treatment protocols. Ig variable (VH) gene sequences
      analysis has previously shown the tumor cell of multiple myeloma to be
      postfollicular, with mutated homogeneous clonal sequences indicating no
      continuing exposure to the somatic hypermutation mechanism, and this was
      confirmed in 7 of 7 patients. Comparison of the VH gene sequences in the
      monoclonal cells in MGUS yielded a different result, with 3 of 7 patients
      demonstrating mutated heterogeneous sequences consistent with the tumor cells
      remaining under the influence of the mutator. In 1 of 3 of these patients, an IgM
      positive precursor cell was identified that expressed heterogeneous VH sequences
      similar to those of the isotype-switched plasma cell. These results indicate that
      the clonal cells in MGUS differ from those in myeloma and suggest that the
      difference may reflect malignant potential.

PMID- 8555501
TI  - The ontogeny of key endoplasmic reticulum proteins in human embryonic and fetal
      red blood cells.
AB  - Recently, using immunohistochemical methods, we surprisingly found that
      endoplasmic reticulum glucose-6-phosphatase is present in human embryonic and
      fetal red blood cells (RBCs) but not in adult RBCs. The fact that an endoplasmic
      reticulum enzyme, whose major site of expression in adults is the liver, is
      present in human embryonic and fetal RBCs, particularly nucleated cells,
      indicated that it would be sensible to determine whether these cells also contain
      other endoplasmic reticulum enzyme systems normally found in adult liver.
      Therefore, we have studied the expression of other endoplasmic reticulum proteins
      and found that human embryonic and fetal RBC precursors contain other protein
      components of the glucose-6-phosphatase system, ie, the phosphate and glucose
      transport proteins as well as other enzymes (eg, uridine diphosphate
      glucuronosyltransferases, cytochrome P450 isozymes, nicotinamide adenine
      dinucleotide phosphate cytochrome P450 oxidoreductase, and prostaglandin H
      synthase). In addition, we also found the predominantly cytosolic markers 15
      hydroxyprostaglandin dehydrogenase, prostaglandins PGE2 and 13,14-dihydro-15-keto
      PGE2. The expression of key enzymes that control glucose production,
      detoxification of endobiotics and xenobiotics, and the regulation of
      prostaglandin levels in embryonic and early fetal RBCs means that these cells may
      have an important role in protecting the developing conceptus before it
      establishes an efficient circulation and before all tissues fully express their
      normal complement of these enzymes.

PMID- 8555502
TI  - Adhesion of sickle neutrophils and erythrocytes to fibronectin.
AB  - The pathophysiology of vaso-occlusive crisis in sickle cell disease involves
      interactions among blood cells, plasma proteins, and vessel wall components. The
      initial goal of this work was to quantify the adhesion of sickle red blood cells
      (RBCs) to fibronectin immobilized on glass under both static and dynamic shear
      stress conditions. High-power microscopic inspection of static assay plates
      showed striking numbers of adherent neutrophils as well as RBCs. Sickle
      neutrophils and RBCs were significantly more adherent to fibronectin than the
      corresponding normal cells in static adhesion assays. Adhesion of both sickle
      neutrophils and sickle RBCs in dynamic adhesion assays was promoted by a period
      of static incubation preceding initiation of shear stress conditions. Adherent
      neutrophils remained attached at shear stresses up to 51 dyne/cm2; most adherent
      RBCs were attached at shear stresses up to 13 dyne/cm2, but detached at a shear
      stress of 20 dyne/cm2. Sickle neutrophil adhesion was enhanced significantly by
      autologous plasma. Elevated levels of plasma interleukin-6 (IL-6; but not IL-1 or
      IL-8) were found in 6 of 9 sickle cell disease samples examined, and elevated
      levels of tumor necrosis factor were found in 2 of 9 samples. Plasma IL-6 levels
      correlated positively with both the number of sickle neutrophils adherent to
      fibronectin and the ability of sickle plasma to enhance adhesion of normal
      neutrophils to fibronectin. These data suggest possible roles for neutrophil
      activation and for fibronectin in mediating sickle neutrophil and RBC adhesion.

PMID- 8555500
TI  - Hypoxic induction of gene expression in chronic granulomatous disease-derived B
      cell lines: oxygen sensing is independent of the cytochrome b558-containing
      nicotinamide adenine dinucleotide phosphate oxidase.
AB  - Reduced oxygenation of a variety of cells results in transcriptional upregulation
      of several genes, including the hematopoietic hormone erythropoietin, the
      angiogenic vascular endothelial growth factor (VEGF), and glycolytic enzymes such
      as aldolase. Recently, the heme protein cytochrome b558 of the nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase complex has been proposed as a key
      component of the oxygen-sensing mechanism. Cytochrome b558 consists of the
      p22phox and gp91phox subunits and is essential for superoxide generation in
      phagocytes and B lymphocytes. Mutations in these subunits result in cytochrome
      b558-negative chronic granulomatous disease (cytb- CGD), an inherited disorder in
      humans characterized by reduced microbicidal activity due to deficient superoxide
      generation. To test whether NADPH oxidase is involved in oxygen sensing, we
      exposed wild-type B-cell lines as well as cytb- CGD-derived B cell lines,
      deficient in either p22phox or gp91phox, to hypoxia (1% oxygen) or CoCl2 (100
      mumol/L) and compared the mRNA levels of VEGF and aldolase with the untreated
      controls. Northern blot analysis revealed unimpaired basal and inducible
      expression of VEGF and aldolase mRNA in all four cytb- CGD-derived B-cell lines
      compared with wild-type cells. Furthermore, reconstitution of cytochrome b558
      expression in cytb- CGD-derived B cells by transfection with p22phox or gp91phox
      expression vectors did not modify VEGF and aldolase mRNA expression. Thus,
      cytochrome b558 of the NADPH oxidase complex appears not to be essential for
      hypoxia-activated gene expression and can be excluded as a candidate for the
      putative universal oxygen sensor.

PMID- 8555503
TI  - Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a
      single intravenous injection of interleukin-8.
AB  - Interleukin-8 (IL-8) is a chemoattractant cytokine involved in chemotaxis and
      activation of neutrophils. Because in vivo administration of IL-8 induces
      mobilization of hematopoietic stem cells in mice, we assessed the mobilizing
      properties of IL-8 in rhesus monkeys. Recombinant human IL-8 was administered as
      a single intravenous injection at doses of 10, 30, and 100 micrograms/kg to
      rhesus monkeys (age, 2 to 3 years; weight, 2.5 to 4.5 kg). Venous blood samples
      were obtained at time intervals ranging from 1 to 480 minutes after IL-8
      administration. Cell counts, colony-forming unit-Mix assays, and fluorescence
      activated cell sorter analysis were performed. Plasma was harvested to assess IL
      8 levels. A time-controlled bolus intravenous injection of 100 micrograms IL-8
      per kilogram of body weight resulted in peak IL-8 plasma levels up to 5
      micrograms/mL. The calculated half-time life of free IL-8 was 9.9 +/- 2.2
      minutes. IL-8 injection resulted in instant neutropenia that was due to pulmonary
      sequestration, as shown using 99mTc-labeled leukocytes. Within 30 minutes after
      IL-8 injection, neutrophilia developed with counts up to 10-fold greater than
      baseline levels. The numbers of hematopoietic progenitor cells (HPCs) increased
      from 45 +/- 48/mL to 1,382 +/- 599/mL of blood at 30 minutes after injection of
      100 micrograms IL-8 per kilogram of bodyweight (mean +/- SD, n = 8). Individual
      animals showed 10- to 100-fold increase in numbers of circulating HPCs that
      returned to almost pretreatment values (92 +/- 52 CFU/mL) at 240 minutes after
      the injection of IL-8. Immunophenotyping showed no significant changes in
      lymphocyte (sub)populations. A second bolus injection of IL-8 with an interval of
      72 hours resulted in similar numbers of mobilized stem cells as observed after
      the first injection, showing that no tachyphylaxis had occurred. We conclude that
      IL-8 induces mobilization of HPCs from the bone marrow of rhesus monkeys in a
      rapid and reproducible fashion. Therefore, IL-8 may be a potentially useful
      cytokine in the setting of blood stem cell transplantation.

PMID- 8555504
TI  - Stable clonal expansion of T cells induced by bone marrow transplantation.
AB  - The immune mechanisms of T cells regeneration after bone marrow transplantation
      (BMT) and the factors maintaining allogeneic marrow graft in the host are still
      unknown. To pursue this issue, we analyzed T-cell clonality of peripheral blood
      lymphocytes (PBLs) in BMT recipients, using reverse transcription polymerase
      chain reaction with T-cell receptor (TCR) V beta gene segment-specific primers
      and single-strand conformation polymorphism. PBLs from patients and donors showed
      a heterogeneous T-cell population with oligoclonal accumulations of CD8+ T cells.
      When PBLs were cultured in HLA-matched mixed lymphocytes reaction in vitro, no
      distinct clonal expansion was observed. However, after BMT, oligoclonal
      expansions were induced in the recipients in vivo, without a restriction of TCR V
      beta gene usage. Although part of the expansion was transient, the majority was
      repeatedly detected even several months later. Our results suggested that certain
      in vivo mechanisms maintain a stable clonal expansion of distinct T cells in
      marrow recipients. We also found in a single patient with graft-versus-host
      disease a replacement of expanded clones by other clones during follow-up.
      Diminishing numbers of accumulation clones were found in long-term marrow
      recipients, indicating a general tendency for clonal expansion to subside
      progressively. Considered together, our data suggest the involvement of clonally
      expanded T cells in lymphoid regeneration and in acute and chronic immune
      responses after BMT.

PMID- 8555505
TI  - The probability of finding a suitable related donor for bone marrow
      transplantation in extended families.
AB  - In bone marrow transplantation, the advantages of family donors over unrelated
      donors are threefold. (1) Family donors are better matched because they share
      complete haplotypes. (2) The time between the start of the search and the actual
      transplantation can be much shorter than for unrelated donors. (3) Related bone
      marrow transplantation is cheaper. We developed a procedure for calculating the
      probability of finding a suitable donor among cousins and blood-related aunts and
      uncles (the extended family). The procedure calculates the following
      probabilities (P): (1) P that any blood-related uncle or aunt is a suitable
      donor, (2) P that a suitable donor exists in all blood-related uncles/aunts (from
      [1]), (3) P that any cousin is a suitable donor (as in [1]), (4) P that a
      suitable donor exists in all cousins (from [3]), (5) P that a suitable donor
      exists in the entire extended family (from [2] and [4]). Additionally, we discuss
      the suitability of this procedure in the daily practice of donor procurement. The
      procedure is also suitable to search for family donors who have a single antigen
      mismatch with the patient. We also discuss the differences between our method and
      the one recently described by Kaufman (Bone Marrow Transplant 15:279, 1995).

PMID- 8555506
TI  - Differential mobilization of myeloma cells and normal hematopoietic stem cells in
      multiple myeloma after treatment with cyclophosphamide and granulocyte-macrophage
      colony-stimulating factor.
AB  - Peripheral blood stem cells (PBSCs) mobilized with high-dose chemotherapy and
      hematopoietic growth factors are now widely used to support myeloablative therapy
      of multiple myeloma and effect complete remissions in up to 50% of patients with
      apparent extension of event-free and overall survival. Because tumor cells are
      present not only in bone marrow, but also in virtually all PBSC harvests, it is
      conceivable that autografted myeloma cells contribute to relapse after
      autotransplants. In this study, the kinetics of mobilization of normal
      hematopoietic stem cells were compared with those of myeloma cells present in
      PBSC harvests of 12 patients after high-dose cyclophosphamide and granulocyte
      macrophage colony-stimulating factor administration. CD34+ and CD34+Lin-Thy+ stem
      cell contents were measured by multiparameter flow cytometry, and myeloma cells
      were quantitated by immunostaining for the relevant Ig light chain and by a
      quantitative polymerase chain reaction for the myeloma-specific CDRIII sequence.
      Results indicated marked heterogeneity in the percentages of mobilized stem cells
      among different patients (0.1% to 22.2% for CD34+ cells and 0.1% to 7.5% for
      CD34+Lin-Thy+ cells, respectively). The highest proportions of hematopoietic
      progenitor cells were observed early during apheresis, with 9 of 12 patients
      mobilizing adequate amounts of CD34+ cells for 2 autotransplants (> 4 x 10(6)/kg)
      within the first 2 days, whereas peak levels (percent and absolute numbers) of
      myeloma cells were present on days 5 and 6 (0.5% to 22.0%). During the last days
      of collection, mobilized tumor cells exhibited more frequently high labeling
      index values (1% to 10%; median, 4.4%) and an immature phenotype (CD19+). The
      differential mobilization observed between normal hematopoietic stem cells and
      myeloma cells can be exploited to reduce tumor cell contamination in PBSC
      harvests.

PMID- 8555507
TI  - Epstein-Barr virus transmission from a blood donor to an organ transplant
      recipient with recovery of the same virus strain from the recipient's blood and
      oropharynx.
AB  - A previous study (Savoie et al, Blood 83:2715, 1994) identified eight transplant
      patients who acquired Epstein-Barr virus (EBV) infection during the
      peritransplant period. Three of these patients subsequently developed B-cell
      lymphoproliferative disease within 4 months of transplantation. Among these,
      there was a 16-year-old liver transplant patient who was negative for EBV at the
      time of transplant and who received an EBV-negative organ. After transplant, this
      patient was transfused with 9 U of packed red blood cells. Eight of the donors
      were EBV-positive and one was EBV-negative. We succeeded in obtaining spontaneous
      lymphoblastoid cell lines (LCLs) from the blood of three of these donors, one of
      whom also yielded a cord-blood line established with his throat-wash EBV. Blood
      from a fourth donor did not yield an LCL, but his throat washing did have
      transforming activity when inoculated onto cord-blood leukocytes. We initially
      could establish spontaneous LCLs only from the recipient's blood. However, a
      throat-wash sample taken 11 weeks later did show transforming activity. The
      recipient was shown to have acquired the EBV infection from one of eight EBV
      seropositive blood donors. Analysis of fragment length polymorphisms after
      polymerase chain reaction amplification of the EBV BamHI-K fragment was used to
      establish strain identity. Western blot analysis for existence of size
      polymorphisms in three classes of Epstein-Barr nuclear antigens (EBNA-1, EBNA-2,
      and EBNA-3) confirmed the DNA results. It is noteworthy that the blood donor
      responsible for transmitting his EBV strain to the recipient had experienced
      clinical infectious mononucleosis 15 months before donating blood. Our results
      may, thus, indicate a requirement for leukodepletion of blood destined for
      immunosuppressed EBV-negative patients. Finally, blood donors with a recent
      history of infectious mononucleosis should probably be identified so that their
      blood is not given to EBV-negative transplant patients.

PMID- 8555508
TI  - The origin of IgG production and homogeneous IgG components after allogeneic bone
      marrow transplantation.
AB  - Pediatric recipients (n = 25) of an allogeneic bone marrow (BM) graft were
      selected on the basis of informative IgG allotype (Gm) differences between the BM
      donor and the recipient. To investigate the kinetics of the appearance of IgG of
      donor origin and the disappearance of IgG of recipient origin, G1m and G2m
      allotype levels were quantified in sera obtained at regular intervals between 3
      months and 5 years after BM transplantation (BMT). For this quantification, a dot
      immunobinding assay (DIBA) has been developed. In 19 of 22 informative
      recipients, the Gm allotype distribution had reached the range of values expected
      on the basis of the Gm phenotype of the donor within 6 months after BMT.
      Remarkably, IgG of recipient origin persisted in 15 of 18 informative recipients
      until last follow up, ie, for several years after BMT. In addition to the origin
      of total IgG production, the origin of homogeneous IgG components (H-IgG)
      appearing after BMT was investigated. H-IgG of donor origin could be detected as
      early as 3 weeks after BMT, but also H-IgG of recipient origin were present in 8
      of 13 informative recipients for a period of up to 1 year after BMT. We conclude
      that host-type IgG-producing cells were not eradicated by the (myeloablative)
      conditioning regimen and persisted in a high number of graft recipients. It is
      our hypothesis that lack of graft-versus-host disease (GVHD) in the majority of
      these recipients results in the persistence of IgG-producing cells of host
      origin. These observations may be relevant for the evaluation of patients who
      received allogeneic BMT for the treatment of multiple myeloma.

PMID- 8555509
TI  - Lethal murine graft-versus-host disease induced by donor gamma/delta expressing T
      cells with specificity for host nonclassical major histocompatibility complex
      class Ib antigens.
AB  - Although T-cell receptor (TCR) alpha/beta expressing cells have a well-known role
      in graft-versus-host disease (GVHD) generation, the role of TCR gamma/delta
      expressing cells in this process has remained unclear. To elucidate the potential
      function of TCR gamma/delta cells in GVHD, we have used transgenic (Tg) H-2d mice
      (termed G8) that express gamma/delta heterodimers on a high proportion of
      peripheral T cells. In vitro, G8 Tg gamma/delta T cells proliferate to and kill
      C57BL/6 (B6) (H-2b) which express gene products (T10b and T22b) from the
      nonclassical major histocompatibility complex (MHC) class Ib H-2T region. The
      infusion of G8 Tg (H-2Td) TCR gamma/delta cells into lethally irradiated [900 cGy
      total body irradiation (TBI)] B6 (H-2b) mice resulted in the generation of lethal
      GVHD characterized histologically by destruction of the spleen, liver, lung, and
      colon. Lethal GVHD was prevented by the injection of anti-TCR gamma/delta
      monoclonal antibodies. Immunohistochemical analysis of B6 recipients post-bone
      marrow transplantation (BMT) confirmed that G8 Tg TCR gamma/delta cells
      infiltrated GVHD target tissues (skin, liver, colon, and lung) and were absent in
      recipients treated with anti-TCR gamma/delta monoclonal antibodies (MoAbs) but
      not anti-CD4 plus anti-CD8 MoAbs. In contrast, injection of TCR gamma/delta+
      cells into irradiated (900 cGy TBI) B6.A-TIaa BoyEg mice that do not express
      either T10b or T22b did not induce lethal GVHD. Similarly, in a different GVHD
      system in which sublethal irradiation without bone marrow (BM) rescue was used,
      B6 but not B6.A-TIaa/BoyEg mice were found to be susceptible to TCR gamma delta+
      cell mediated GVHD-induced lethality characterized by an aplasia syndrome. These
      results demonstrate that TCR gamma/delta cells have the capacity to cause acute
      lethal GVHD in mice and suggest that nonclassical MHC class Ib gene products
      expressed on GVHD target organs are responsible for G8 Tg TCR gamma/delta+ cell
      mediated lethality.

PMID- 8555510
TI  - Breakthrough candidemia during antifungal treatment with fluconazole in patients
      with hematologic malignancies.

PMID- 8555511
TI  - Clarification of CD3 immunoreactivity in nasal T/natural killer cell lymphomas:
      the neoplastic cells are often CD3 epsilon+.

PMID- 8555512
TI  - Recombinant interleukin-2 infusions and serum IgG subclass levels.

PMID- 8555513
TI  - Passenger B-lymphocyte-induced severe hemolytic disease after allogeneic
      peripheral blood stem cell transplantation.

PMID- 8555514
TI  - Postdischarge surgical site infection surveillance.
AB  - OBJECTIVE: To evaluate three methods for conducting post-discharge surgical site
      infection (SSI) surveillance. DESIGN: Patients undergoing in-patient and day
      patient surgery were prospectively randomized to one of three surveillance
      methods: group 1, patient questionnaire (mailed back); group 2, surgeon follow-up
      card; or group 3, patient questionnaire (telephoned by an infection control
      practitioner [ICP]). There were 200 in-patients and 200 day-patients randomized
      to each group. Evaluation of SSI was conducted 30 days postoperatively. SETTING:
      A 760-bed tertiary care teaching hospital. RESULTS: Questionnaires were sent home
      with 350 patients. Fifteen in-patients and 35 day-patients were excluded; 15 in
      patients and 17 day-patients returned questionnaires early (fewer than three
      weeks postoperation), leaving 54 of 185 in-patients (29.2%) and 25 of 165 day
      patients (15.2%) with timely returns. Seven (three in-patients and four day
      patients) reported symptoms of SSI. Surgeons received cards for 400 patients;
      cards were returned for 118 of 203 in-patients (58.1%) and 142 of 197 day
      patients (72.1%). Twelve (seven in-patients and five day-patients) were reported
      to have developed SSI. ICPS telephoned 332 patients; 187 of 196 in-patients
      (95.4%) and 107 of 126 day-patients (84.9%) were reached in six or fewer
      attempts. Four in-patients and 74 day-patients were lost due to cancellation of
      surgery or no surgical incision. Fourteen (10 in-patients and four day-patients)
      reported symptoms of SSI. For group 1 patients, ICPS spent 17 h distributing
      questionnaires and instructing staff; for group 2, ICPs spent no time
      distributing material; and for group 3, ICPS spent at least 8 h completing data
      forms, 16.5 h on the telephone and 33 h conducting demographic data retrieval
      from the hospital computer. CONCLUSIONS: In this setting, surgeon follow-up cards
      were the most efficient and reliable method for conducting postdischarge SSI
      surveillance. They provided a good rate of return and were time efficient, and
      wound evaluation was done by trained professionals using standard criteria for
      diagnosis of postoperative SSI.

PMID- 8555515
TI  - Surveillance methods for central venous access device-associated infections in
      Canadian pediatric hospitals.
AB  - The most common complication of central venous access device (CVAD) use is
      infection, which occurs in 3 to 48% of hospitalized patients. It is recommended
      that regular surveillance of adverse events with CVADs be conducted, expressed as
      a proportion of 1000 device days and reviewed and acted upon by the institution's
      infection control committee. In the process of developing a CVAD program the
      authors attempted to determine the standard of practice at other Canadian
      pediatric hospitals. A telephone survey of infection control practitioners (ICPS)
      or CVAD nurses in 15 university-affiliated Canadian pediatric hospitals was
      conducted using a standard questionnaire. Fourteen hospitals (93%) conduct
      surveillance for infections associated with CVADS. One program, a pilot project,
      follows mechanical complications of CVAD use. Eleven centres conduct
      comprehensive surveillance; in three, selected patients are followed. Only three
      programs have sufficient staff to follow out-patients. Definitions for CVAD
      infections varied widely. A positive blood culture from the catheter is
      sufficient for diagnosis in eight of the 14 centres (57%); the rest use Centers
      for Disease Control and Prevention (CDC) or modified CDC criteria. In the four
      centres where CVAD line days are collected on most or all patients, multiple
      personnel other than the ICP assist in data collection. Four hospitals report
      number of infections per 100 discharges, four report absolute number of
      infections and two use more than one denominator. Surveillance methods rely
      largely on paper-based chart and microbiology record review; no hospital had
      access to computerized patient data for direct data retrieval. Eight centres have
      CVAD committees for policy development, and all 15 have or are developing
      hospital-wide protocols for CVAD use. Canadian pediatric hospitals recognize the
      importance of CVAD infections, but it appears that insufficient resources are
      available to meet recommended data collection methods. Interhospital comparison
      of rates is not possible at present because of variation in definitions and
      denominators and in types of patients surveyed.

PMID- 8555516
TI  - CHICA-Canada--an historical perspective: 1976 to 1994.

PMID- 8555518
TI  - Impact of new education requirements on recertifiers.

PMID- 8555517
TI  - Medical devices bureau: latex allergies project.

PMID- 8555519
TI  - 200 cases with a new breathing pacemaker dispel myths about diaphragm pacing.

PMID- 8555520
TI  - Importance of adaptive stimulation of the latissimus dorsi muscle in
      cardiomyoplasty.
AB  - During cardiac synchronized latissimus dorsi (LD) stimulation, adaptive duration
      (AD) allows the pulse train length to be set as a percentage of the cardiac
      cycle. The LD contraction duration adjusts to variations in heart rate (HR). The
      effects of AD on LD work output and blood flow (BF) were investigated in nine
      dogs that underwent skeletal muscle ventricle (SMV) construction. The SMVs were
      stimulated according to the cardiomyoplasty protocol. BF and the pressure
      increase (delta P) generated during SMV contraction were monitored biweekly for 3
      months. SMV contraction time increased significantly after training (P < 0.0001).
      The trained SMV could only partially contract at duration settings of 25% and
      30%. Before training, the increase in mean pressure and BF during 35% AD
      increased proportionally with increasing HR. After training, BF and mean pressure
      decreased with increasing HR because of reduced peak pressure generation during
      partial SMV contractions. When duration was fixed at 200 msec, BF increased with
      HR to 80 bpm but decreased with additional increases in HR. At high rates and
      fixed duration, inadequate relaxation between contractions resulted in the
      inefficient muscle performance and reduced BF. AD did not impair BF and allowed
      the appropriate autoregulatory response to occur in the trained and untrained LD
      so that the supply-to-demand ratio did not become compromised over a large range
      of HR.

PMID- 8555521
TI  - A total delivery system of genetically engineered drugs or cells for diseased
      vessels. Concept, materials, and fabricated prototype device.
AB  - The development of a percutaneous procedure using a catheterized system for
      diseased vessels has been increasingly in demand in conjunction with gene therapy
      using genetically engineered drugs (antisense) and cells. The authors' strategic
      concept realizes revascularization at narrowed, diseased sites and delivery of
      drugs or cells into the diseased tissues or targeted cells. An inflatable, drug
      releasing double balloon is installed at the tip of a catheter. The outer
      balloon, fabricated with micropores (diameters of 20 and 30 mm) by an excimer
      laser ablation technique, releases a viscous solution containing a photoreactive
      polymer and drug or cells on inflation of the inner balloon. A photoresponsive
      water-soluble polymer, molecularly designed for its ability to achieve prolonged
      local residency of antisense DNA at the tissue level and enhanced transmembrane
      transport at the cellular level, is premixed with antisense oligonucleotide drug.
      On light irradiation, the nonionic polymer is reversibly converted to a
      positively charged polymer that can be complexed with highly negatively charged
      antisense DNA (c-myb), which may enhance the transmembrane delivery of antisense.
      On cessation of irradiation, the complex slowly dissociates to function
      intracellularly as an antisense drug, resulting in inhibition of cell
      proliferation. Thus, our integrated, dual-function balloon system may contribute
      to mechanical dilatation gene therapies at diseased vessels.

PMID- 8555522
TI  - Rapid neointima formation with elastic laminae similar to the natural arterial
      wall on an adipose tissue fragmented vascular prosthesis.
AB  - A vascular prosthesis that can induce a neointima similar to a natural arterial
      wall is reported. The authors have developed a sealing method using autologous
      tissue fragments. The sealed graft showed many advantages, with characteristic
      neointima formation in an animal study. The grafts were implanted in the thoracic
      descending aortae of 40 dogs and were removed from 1 hour to 608 days after
      implantation. Another 40 dogs, used as controls, had a fabric graft implanted
      using the preclotting method. The luminal surface of the sealed graft was
      completely endothelialized and the original adipose tissue fragments were
      absorbed within 1 month. Smooth muscle cells infiltrated and proliferated at the
      same time as endothelialization took place. Most of the smooth muscle cells were
      arranged in parallel rows and oriented circumferentially within the graft. At 1
      month, elastic fibers appeared around the smooth muscle cells near the
      anastomotic sites. In the long-term specimens, these elastic fibers constituted a
      fine lamina in the neointima. Intimal hyperplasia and degenerative changes in the
      neointima were not observed. These results indicated that the sealing method
      could induce a very stable neointima with a smooth muscle cell layer and elastic
      laminae similar to a natural arterial wall within a short period of time
      throughout the graft wall, with maintenance of the neointima for a long period of
      time after implantation.

PMID- 8555523
TI  - Compliance and formation of distal anastomotic intimal hyperplasia in Dacron mesh
      tube constricted veins used as arterial bypass grafts.
AB  - Dilated and varicose veins constricted with a Dacron mesh tube were successfully
      used as arterial bypass grafts to avoid nonautogenous vascular prostheses. Mesh
      constriction has also been used to adapt the venous graft lumen to the diameters
      of grafted arteries. The influence of the external mesh on the wall elasticity of
      such venous grafts and the reactions of the host artery were not investigated.
      Elastic properties of mesh constricted autologous veins used as arterial grafts
      in femoropopliteal reconstructions, as well as consecutive formation of distal
      anastomotic intimal hyperplasia (DAIH), were investigated in this experiment.
      Twenty-four autologous venous grafts were implanted in 12 sheep. Grafts were left
      natural (Groups 1 and 3) or were constricted with an external Dacron mesh (Groups
      2 and 4); their diameters were left unchanged (Groups 1 and 2) or were matched to
      the diameter of the host artery (Groups 3 and 4). Wall elasticity of the graft,
      distal anastomosis, and distal artery were measured by locally applied crystal
      transducers during surgery and follow-up. Formation and localization of DAIH was
      evaluated histomorphologically after a median of 8.3 months. Graft wall
      elasticity was found to be lower (54.6 vs. 147.9, P = 0.006) and overall DAIH was
      found to be higher in mesh tube grafts (49.42 vs. 20.8 microns, P = 0.001, Mann
      Whitney U-test). No differences in elasticity and DAIH formation were observed
      between grafts with adapted and large diameters. Constriction of venous grafts by
      a Dacron mesh tube reduces graft wall elasticity and promotes formation of DAIH.
      To avoid such an increased mismatch in compliance while making use of the
      advantages of this method, the external mesh tube must not be brought close to
      the distal anastomotic area itself.

PMID- 8555524
TI  - Histopathologic findings in synthetic and biologic explanted grafts used in
      peripheral arterial reconstruction.
AB  - Surgically explanted vascular grafts, including 47 autografts, 14 allografts, 103
      chemically processed human umbilical vein (HUV) grafts, and 406
      polytetrafluoroethylene (PTFE) grafts, were studied histopathologically.
      Autografts, HUV, and PTFE grafts were implanted mostly in the femoropopliteal
      position, whereas allografts were used as a blood access for hemodialysis. The
      main cause for explantation in autografts (53.6%), HUV (74.8%), and PTFE (61.3%)
      was thrombosis, whereas allograft failure was usually related to aneurysmal
      degeneration (72.7%). The infection rates of HUV (20.9%) and PTFE (25%) grafts
      were higher than those of autografts (4.8%) and allografts (9.1%). Furthermore,
      bacterial colonization occurred more frequently in HUV (63.9%) and PTFE (64.7%)
      than in autografts (6.7%) and allografts (0%). Leukocyte infiltration was
      detected mostly in HUV (39.4%) and PTFE (27%) explants. Autografts and allografts
      both showed a 7.1% rate of lipid uptake, whereas lipid retention was observed in
      84.9% of HUV and 79.8% of PTFE grafts. These results suggest that biologic
      vascular grafts are to be used preferentially in small diameter arterial
      reconstruction because of their resistance to bacterial colonization and lipid
      uptake.

PMID- 8555525
TI  - Reconstruction of a hybrid vascular graft hierarchically layered with three cell
      types.
AB  - Hybrid grafts with hierarchically incorporated endothelial cells (ECs), smooth
      muscle cells (SMCs), and fibroblasts (FCs), were developed, and the cellular
      behavior and ultrastructure of the regenerated extracellular matrix (ECM) of the
      grafts were investigated in vivo. Two models of hybrid vascular grafts were
      constructed on knitted Dacron grafts (internal diameter, 4 mm; length, 6 cm) in
      vitro. Model I grafts were hierarchically structured with a confluent monolayer
      of ECs, a middle layer of SMCs, and an outer layer of FCs. Model II consisted of
      a confluent EC monolayer and a homogeneously mixed layer composed of SMCs and FCs
      prelabeled with fluorescent lipids. The designed artificial ECM was a mixed gel
      of type I collagen and dermatan sulfate. Both grafts were implanted bilaterally
      in the carotid arteries of 11 dogs for up to 12 weeks without anticoagulant.
      Regardless of model type, patent grafts (n = 18 of 22 implanted grafts) were
      completely endothelialized. In model II grafts at 4 weeks, SMCs migrated to the
      subendothelial layer, whereas labeled FCs migrated to an outer layer. Observation
      of model I grafts at 12 weeks showed that most of the collagen fibers in the
      luminal surface layer were longitudinally oriented, but those in deeper layers
      tended to orient circumferentially, and that newly generated elastic tissues were
      composed of many concentric laminae. SMCs of both grafts at 12 weeks were
      predominantly of the contractile phenotype. Thus, hybrid grafts incorporating
      intimal-, medial-, and adventitial-type layers can enhance the process of
      arterial wall reconstruction.

PMID- 8555526
TI  - Development of a vascular prosthesis for a growing child. A graft expandable in
      vivo.
AB  - Specially designed vascular prostheses that can be dilated after implantation
      using a percutaneous transluminal angioplasty (PTA) balloon catheter have been
      developed. The grafts are made of woven polyester fiber fabrics, the
      circumferential yarns of which consist of two different types of polyester fiber
      bundles: One is a straight weak bundle, the other is a strong bundle wound around
      the former. The graft with an initial diameter of 6 mm could be dilated to 9 mm
      by luminal inflation of the balloon four to five times at 10 atmospheres (atm) in
      vitro. After disrupting the weak bundle by the dilatation procedure, the strong
      bundles were straightened, which maintained the enlarged diameter of the new
      caliber. Grafts of 6 mm in initial diameter implanted into the thoracic aortas of
      mongrel dogs for 3 months also could be dilated in vivo by inflating the PTA four
      to five times at 15 atm, as found in the vitro study. Macroscopic observation
      revealed that, around the dilated grafts, only a tiny hematoma was formed and
      nominal subsequent bleeding was observed, which indicated that the dilatation
      procedure was performed safely. The graft, which enables adaptation of the
      hydrodynamic property of the graft to the increased blood flow by PTA after
      implantation, is applicable in a growing child.

PMID- 8555527
TI  - Dynamic biventricular response to alterations in preload in patients undergoing
      left ventricular device implantation.
AB  - Ventricular interdependence is important for the successful use of a left
      ventricular assist device (LVAD) because the filling of the device depends on
      right ventricular (RV) function as well as the interactions between the
      ventricles. The pulmonary arterial (PAP) and systemic arterial (AP) response to
      inferior vena caval (IVC) occlusion before and after insertion of an LVAD in 15
      patients was used to "dissect out" the determinants of these interactions. PAP
      and AP were recorded during each IVC occlusion and peak systolic values
      calculated for each beat. Linear regression analysis was used to calculate the
      slope (k) between peak systolic AP values and peak systolic PAP values. k, a
      measure of preload responsiveness of the heart, is predominantly linear. k is
      relatively "flat" in selected LV failure patients pre-LVAD but increases
      significantly (P < 0.001) after LVAD (0.67 +/- 0.55 vs. 2.71 +/- 1.39). The
      increase in this parameter after LVAD suggests that the loss of RV-to-LV
      ventricular interdependence in patients with congestive heart failure appears to
      recover somewhat once an LVAD is inserted.

PMID- 8555528
TI  - Dynamic systemic vascular resistance in a sheep supported with a Nimbus AxiPump.
AB  - Changes in systemic vascular resistance (SVR) in response to diminished pulse
      perfusion were analyzed over a dynamic range of flow conditions. An axial flow
      LVAD (Nimbus AxiPump, Rancho Cordova, CA) was implanted in a sheep for 28 days,
      during which time SVR was determined over several conditions of posture and
      excitability. Total arterial resistance (TR) was calculated dynamically as an
      index of SVR by analysis of pump flow in diastole, and systemic pressure
      estimated from the characteristic pressure-flow-speed relation of the AxiPump. TR
      was evaluated over a range of flow rates, including maximum flow--for which the
      pressures and flows were essentially nonpulsatile. Throughout the course of
      support, and independent of pulsatility, TR dropped when the sheep stood and was
      significantly lower than that in the sitting position (P < 0.01). Response to
      excitement followed the same trend: TR was significantly higher during agitation
      than during normal temper (P < 0.01). In spite of changes in pulse pressure and
      flow rate, SVR changes occurred according to expected physiologic responses for
      pulsatile perfusion. Because pump flow and pressure are sensitive to afterload,
      the results of these studies suggest that pump speed control must compensate for
      changes in SVR to maintain acceptable perfusion.

PMID- 8555529
TI  - Right ventricular performance is impaired by full assist of left heart bypass.
      Analysis of right ventricular performance against change in afterload in heart
      failure models.
AB  - The purpose of this study was to assess right ventricular (RV) performance during
      left heart bypass (LHB) and to determine the optimum LHB driving conditions to
      preserve RV performance. LHB was established with a centrifugal pump in eight
      mongrel dogs weighing 11-19 kg. Failing heart models were induced by normothermic
      aortic clamping for 20 min. RV volume was measured by a conductance catheter, and
      RV performance was evaluated by two parameters. One was the slope of the RV end
      systolic pressure-volume relationship (ESPVR) as a load independent index, and
      the other was the peak RV pressure (PRVP)-RV stroke volume (RVSV) relationship as
      a "force-velocity relationship." These parameters were measured during varying
      assist ratios of LHB at 0% to 100% of pulmonary artery flow, and varying
      afterload as induced by bilateral intrapulmonary balloon inflation. In failing
      hearts, RV ESPVR showed an inverse correlation, with the assist ratio of LHB
      significantly decreasing from 4.23 +/- 1.35 (mmHg/ml) to 3.52 +/- 1.30 (mmHg/ml;
      P < 0.05) after 100% LHB assist. The correlation between PRVP and RVSV also was
      inversely linear, the slope of this correlation becoming significantly steeper
      after 100% LHB assist compared to that without LHB (-0.131 +/- 0.042 vs. -0.051
      +/- 0.038, P < 0.005). These two slopes intersected, and this intersection was
      considered the critical point of afterload above which RVSV was decreased by LHB
      compared to that without LHB. In addition, reducing the assist ratio made the
      slope of the PRVP-RVSV correlation significantly more gentle (70%: -0.072 +/-
      0.037 vs. 100%: -0.131 +/- 0.042, P < 0.05), with the intersection of the two
      slopes shifting rightward (i.e., higher afterload). Consequently, the critical
      level of afterload at 70% LHB assist was significantly higher than that at 100%
      LHB assist (70%: 38.1 +/- 6.9 vs. 100%: 29.2 +/- 6.8, P < 0.05). Therefore, RV
      performance against afterload was improved by reducing the assist ratio of LHB.
      This study demonstrates that RV performance is impaired by full LHB assist if the
      RV afterload is above the critical level, and that reducing the assist ratio may
      improve RV performance against afterload.

PMID- 8555530
TI  - In vivo measurements of skeletal muscle in a linear configuration powering a
      hydraulically actuated VAD.
AB  - Linear contracting skeletal muscle can provide more power and physiologic
      efficiency for cardiac assistance than muscle wrapping configurations. In this
      study, the insertion of the porcine latissimus dorsi muscle was removed from the
      humerus and reattached to a muscle powered ventricular assist device (MVAD),
      consisting of a mechanical to hydraulic piston energy convertor coupled to a
      Thoratec VAD. Effects of muscle preload stretch and thoracodorsal nerve
      stimulation parameters on in vivo unconditioned muscle work and MVAD stroke
      volume were studied. Stroke work increased linearly with muscle preload, and the
      slope of this relationship (Mprsw) provided an index of muscle "contractility,"
      similar to the preload-recruitable stroke work relationship for the heart. With 5
      V, 220 microseconds stimulation pulses over a 200 msec contraction period at 60
      bpm, the Mprsw increased with stimulation frequencies from 0.055 J/cm at 30 Hz to
      0.149 J/cm at 60 Hz, and to 0.212 J/cm at 90 Hz. Stroke work up to 1 J was
      achieved during muscle shortening of 2.5 cm with forces up to 6 kgf and energy
      convertor pressure of 112 psi (approximately 760 kPa). This produced an ejected
      MVAD stroke volume of 40 ml into a systolic pressure of 92 mmHg on a mock loop,
      at a filling pressure of 10 mmHg. The MVAD is designed as an alternative to
      cardiac transplantation, to provide completely implantable circulatory support
      free from batteries and other power conditioning hardware required with
      electromechanical systems.

PMID- 8555531
TI  - Development and evaluation of components for a totally implantable artificial
      heart system.
AB  - The authors have been developing an electrohydraulic (EH) artificial heart system
      for total implantation. This system consists of intrathoracic ventricles, an
      abdominally placed EH actuator, flexible silicone oil conduits, externally
      coupled transcutaneous energy transfer (TET) system, transcutaneous optical
      telemetry (TOT) system, internal battery, and internal control drive unit.
      Fitting was evaluated in chronic animal experiments as a pneumatic system in 11
      goats weighing 55.2 +/- 4.2 kg and 3 calves of 52.3 +/- 1.2 kg. The longest
      survival time in calves was 111 days, and that in goats was 51 days. The
      assembled EH pump was implanted in two goats of 49 and 50 kg as an acute
      experiment, and 4.2-6.7 L/min of cardiac output was maintained. For the TET
      system, an internal coil 3 cm in diameter was implanted to make an arch covered
      by skin. Electric energy was transmitted from the external to the internal coil,
      and energy of about 20 W was carried through wires to an external load. The DC-to
      DC efficiency of the system was 76-83% for 40 days. The TOT system with internal
      light emitting diodes and external photodiodes also was evaluated in a goat.
      Disalignment of up to 12 mm was tolerated. Although more improvement is
      necessary, most of the components showed characteristics desirable for a totally
      implantable system.

PMID- 8555532
TI  - Endothelial cell seeding with rotation of a ventricular blood sac.
AB  - Successful establishment of a durable endothelial cell (EC) monolayer inside a
      ventricular blood sac requires homogeneous coverage of the entire luminal surface
      with attached cells. For this purpose, a new device was developed that slowly
      rotates a fully assembled cardiac prosthesis with three degrees of freedom. We
      seeded ECs derived from human adipose tissue at a density of approximately 3.5 x
      10(4) cells/cm2 onto the surfaces of polyurethane-made blood sacs and "ersatz"
      bladders (consisting of T-25 tissue culture flasks). The kinetics of cell
      attachment, spreading, and proliferation were determined using video microscopy
      combined with image analysis and cell viability assays. After 60 min of seeding
      at 5-10 rotations/hr, the plating efficiency inside the blood sacs was 35.7 +/-
      11%, with cell viability remaining approximately 90 +/- 5%. After 3 hr, when the
      plating efficiency reached a plateau (approximately 70%), the rotation was
      stopped and the ECs were allowed to spread and proliferate under static
      conditions. Within 48 hr, the entire luminal surface was evenly covered by a
      confluent EC monolayer. Our long-term studies show that with a proper feeding
      schedule, such an EC monolayer can be maintained intact in vitro for more than 2
      weeks.

PMID- 8555533
TI  - Use of the Nippon-Zeon pneumatic ventricular assist device as a bridge to cardiac
      transplantation.
AB  - The Nippon-Zeon (NZ) ventricular assist device is a sac type, air driven,
      heterotopic, external pump. Its performance has been evaluated in Japan as a
      bridge to myocardial recovery. Few data are available on the device as a bridge
      to heart transplantation. Since 1991, 10 patients (9 men) were bridged to heart
      transplantation with NZ, all in biventricular support. The mean age was 39 +/- 13
      years (range, 21-60 years), mean body weight was 75 +/- 13 kg (range, 51-95 kg).
      Five patients had a dilated cardiopathy, and five were ischemic (three acute
      myocardial infarctions). Despite maximal inotropic support, including enoximone
      in seven, epinephrine in three, and intraaortic balloon pumping in one, eight
      patients were anuric, three were in acute hepatic failure, and three were
      intubated. Preoperative hemodynamic and biologic values were: cardiac index, 1.57
      +/- 0.4 l/min/m2; pulmonary capillary wedge pressure, 34 +/- 5 mmHg; creatinine,
      200 +/- 80 mumol/l; blood urea nitrogen, 17.5 +/- 8 mmol/l; total bilirubin 36 +/
      6 mumol/l; aspartate aminotransferase, 1,000 +/- 2,000 IU/l. In all patients, a
      biventricular assist device was implanted without the use of cardiopulmonary
      bypass. Improvement occurred immediately in all but one. Mean left ventricular
      flow was 4.5 +/- 0.8 l/min. Anticoagulation was maintained with intravenous
      heparin. Recently for bleeding was required in one case (10%), and two patients
      had positive blood cultures that were successfully treated. There was no
      mechanical failure. Hemolysis was not significant (lactate dehydrogenase, 378 +/-
      50 IU/l; plasma-free hemoglobin below 10 mg/dl). Each device was free of thrombi
      and deposits at time of explantation. One patient died while on assist. Nine
      patients (90%) were transplanted after 11 +/- 8 days (range, 1-32 days). Three
      died early after transplantation, one of graft failure, two of sepsis. Six
      patients (66%) could be discharged. The follow-up ranges from 7 to 28 months. NZ
      is a simple, reliable, pneumatic device driven by a light, silent console; it can
      be rapidly implanted without cardiopulmonary bypass in patients in desperate
      condition who are awaiting cardiac transplantation. The difficulty of patient
      rehabilitation while using this device should limit the duration of support to
      weeks to allow the patient to be in optimal condition for heart transplantation.

PMID- 8555534
TI  - Myocardial tolerance to mechanical actuation is affected by biomaterial
      characteristics.
AB  - Direct mechanical ventricular actuation (DMVA) uses a pressure regulated heart
      cup, fabricated from silicone rubber (SR) for mechanical massage of the heart.
      Because DMVA has demonstrated potential for long-term circulatory support,
      investigations are currently exploring the use of more durable materials for
      fabricating DMVA heart cups. This study assessed the acute effects of heart cups
      fabricated from SR versus polyurethane (PU) on the myocardium. Dogs (n - 18)
      received DMVA for 4 hr of ventricular fibrillation (VF) using either SR (n = 10)
      or PU (n = 8) cups. Microspheres were used to determine perfusion during sinus
      rhythm (control) and at 2 and 4 hr of support. After support, myocardial biopsies
      were assayed for high energy phosphate content. Results demonstrated that PU cups
      required relatively frequent adjustments in drive line parameters that were
      likely due to material softening during PU cup support. Both PU and SR cups
      achieved similar hemodynamics during 4 hr of support. Myocardial perfusion,
      however, demonstrated a marked hyperemia at 4 hr of PU versus SR cup support.
      Regional high energy phosphate content was significantly decreased in hearts
      supported by PU versus SR cups. These results suggest that the relatively
      compliant characteristics of SR materials are important for achieving effective
      DMVA support without injuring the myocardium.

PMID- 8555535
TI  - Anaerobic threshold in total artificial heart animals.
AB  - The anaerobic threshold represents an objective measure of functional capacity
      and is useful in assessment of pulmonary and cardiovascular dysfunction. This
      study determined the anaerobic threshold in total artificial heart animals and
      evaluated the performance of the total artificial heart system. Five animals with
      total artificial hearts were put under incremental exercise testing after
      exercise training. The intensity of exercise ranged from 2.0 to 4.5 km/hr, with
      an increment of 0.5 km/hr every 3 min. The anaerobic threshold was 6.72 +/- 0.84
      ml/kg/min as detected by the lactate method, and 6.48 +/- 0.79 by the CO2 method.
      The value of the anaerobic threshold in total artificial heart animals implies
      that the performance capacity of a total artificial heart is not sufficient to
      meet the oxygen requirements of vigorously exercising skeletal muscle. The
      protocol does not allow for driving parameter changes during exercise, and this
      situation, combined with the manual mode of the control system used, was
      inadequate to allow the total artificial heart animals to exercise more
      vigorously. Using an automatic control mode might be helpful, as well as
      considering the relationship between indices of oxygen metabolism, such as oxygen
      delivery, oxygen consumption, and oxygen extraction rate, in the control
      algorithms in total artificial heart control systems.

PMID- 8555536
TI  - Efficacy of extracorporeal life support in the setting of adult cardiorespiratory
      failure.
AB  - The efficacy of extracorporeal life support (ECLS, ECMO) in the management of
      severe adult cardiorespiratory failure remains controversial. The purpose of this
      review is to evaluate the authors' institutional experience with ECLS in adult
      patients. Between 1988 and 1993, 65 moribund patients with respiratory (n = 51)
      and cardiac (n = 14) failure were supported with ECLS. Criteria for initiation of
      ECLS were: 90% chance of mortality despite maximal conventional respiratory
      management, good potential for recovery, and age younger than 60 years.
      Venovenous bypass was used in 40 and venoarterial in 25 patients. Respiratory
      management included low rate, low pressure ventilation with an inspired oxygen
      fraction < or = 0.5 and tracheostomy tube placement. Continuous systemic
      heparinization was used, maintaining whole blood activated clotting time (ACT)
      between 180 and 200 sec. Survival data are summarized as follows: pneumonia (n =
      25) 56%, adult respiratory distress syndrome (n = 24) 58%, airway support (n = 2)
      100%, and cardiac support (n = 14) 29%. The most common complication was bleeding
      (68%), which was managed in most patients by reduction of anticoagulation or
      local measures such as packing. Data from survivors and nonsurvivors of ECLS in
      patients with respiratory failure were compared in an attempt to define
      prognostic indicators of improved survival. The only prognostic indicator of
      survival that could be identified was the period of time on the ventilator before
      the initiation of ECLS (survivors = 3.0 +/- 2.4 days, nonsurvivors = 6.1 +/9- 4.0
      days, P < 0.005). It is concluded that ECLS can be a life saving modality for the
      management of severe adult cardiorespiratory failure. Earlier institution of ECLS
      in the course of cardiopulmonary failure may improve outcome.

PMID- 8555537
TI  - Monitoring of blood gases during prolonged experimental cardiopulmonary bypass
      and their relationship to brain pH, PO2, and PCO2.
AB  - Eight adult goats under went 5 hr of normothermic cardiopulmonary bypass (CPB)
      with pulsatile (n = 3) and nonpulsatile flow (n = 5). PaCO2 was maintained at 30
      40 mmHg and blood flow rate at 50 ml/min/kg. Brain tissue pH, PO2, and PCO2,
      arterial and venous blood gases, and other systemic variables were monitored. No
      significant differences in brain electrochemistry between pulsatile and
      nonpulsatile perfusion were observed owing to the large variability of the
      results and the small number of experiments. The overall data for brain tissue
      pH, PO2, and PCO2 were analyzed and compared to the results of arterial and
      venous pH, PO2, and PCO2. Brain acidosis developed at the onset of bypass, and
      the values for brain tissue pH dissociated from those of blood pH, suggesting
      that hemodilution and the initial body response to CPB are involved in its
      development. Brain hypercapnia also developed during CPB, the values of brain
      tissue PCO2 dissociated from those of blood PCO2, and brain hypercapnia appears
      to be secondary to brain acidosis. Brain tissue PO2 closely followed the values
      of PvO2, suggesting that PvO2 can be an indicator of brain tissue PO2 during
      normothermic CPB and must be monitored during the procedure. Brain tissue
      acidosis is evidently related to neurologic dysfunction after CPB, and must be
      addressed. Replacement of the priming solution with whole blood or artificial
      blood, reduction of the priming volume, and application of vigorous pulsatile
      flow appear feasible interventions to mitigate brain tissue acidosis during CPB.

PMID- 8555538
TI  - Asanguineous whole body perfusion with a new intracellular acellular solution and
      ultraprofound hypothermia provides cellular protection during 3.5 hours of
      cardiac arrest in a canine model.
AB  - Temporary cessation of blood flow is a necessary aid for certain complex
      neurosurgical and cardiovascular procedures, and hypothermia is often used to
      help protect against the deleterious effects of ischemia and anoxia. In an
      attempt to protect cellular integrity during ultraprofound hypothermia (< 10
      degrees C) and complete blood substitution, two new crystalloid-colloid blood
      substitutes (Hypothermosol-maintenance [HTS-M] and Hypothermosol-purge [HTS-P])
      have been evaluated. Using extracorporeal bypass, 14 dogs were totally
      exsanguinated during cooling using the HTS-P solution, then perfused (40-85
      ml/kg/min; mean arterial blood pressure = 25-40 mmHg) with either TS-M (Group I,
      n = 11), or with HTS-P as controls (Group II, n = 3) for 3 hr at 7 degrees C.
      During warming, the dogs were autotransfused and observed neurologically and
      biochemically during recovery. All dogs in Group I recovered and eight have
      survived long term (12-80 weeks) without apparent neurologic deficits. In
      contrast, dogs in Group II were more difficult to revive (cardiac resuscitation);
      two survived long term with delayed neurologic recovery. Evaluation of
      biochemical parameters showed only a transient and inconsequential elevation in
      enzymes (e.g., brain, liver, and heart) in Group I compared with the markedly
      greater elevations in Group II. The faster neurologic recovery of dogs treated
      with the "intracellular" maintenance solution supports the biochemical data
      showing the benefits of this type of blood substitute for extending the safe
      limits of hypothermic cardiac arrest to beyond 3 hr.

PMID- 8555539
TI  - Characterization and work optimization of skeletal muscle as a VAD power source.
AB  - Powering a ventricular assist device (VAD) with skeletal muscle in a linear
      configuration will require the understanding of basic muscle mechanics and
      efficient use of available power. Accordingly, a mathematical model incorporating
      aspects of the Hill equation has been developed. This model relates whole muscle
      length, force, velocity, and time during cyclic contraction to investigate
      coupling with a hydraulically actuated VAD. Parameters of the model have been
      determined from in vivo isometric and isotonic measurements of electrically
      stimulated pig latissimus dorsi with the humerus insertion reattached to a
      hydraulic loading system. The in vivo results show an exponential passive force
      length relationship and active isometric forces increasing from 2 to 8 kgf over a
      5 cm change in length. The maximum shortening velocity extrapolated from isotonic
      data in 85 cm/sec. With the experimentally determined parameters, the model
      system of differential equations was optimized computationally. Predicted maximum
      cycle work and corresponding muscle force are nonlinear functions of contraction
      duration; an increase in duration yields little improvement in work output for
      longer contraction times. The model helps clarify VAD system design parameters
      for optimal muscle coupling; for example, the model predicts that operating at
      maximum instantaneous power does not optimize stroke work.

PMID- 8555540
TI  - The effects of radiation therapy on the tissue capsule of soft tissue implants.
AB  - A prosthesis has been developed for cosmesis after lumpectomy surgery for breast
      carcinoma. The device is saline filled and percutaneously adjustable in volume to
      permit an optimal cosmetic result after surgical wound healing. A series of 24
      studies of 18 weeks' duration using the adult rabbit animal model were first used
      to study tissue capsule formation around textured versus smooth surface control
      implants and to evaluate the effects of volume adjustments on the tissue capsule.
      Single or multiple adjustments of implant volume had no effect on tissue capsule
      thickness or morphology. Because lumpectomy surgery is invariably followed by
      radiation therapy, a series of six studies was then conducted to determine the
      effects of a typical course of radiation therapy on tissue capsule formation. One
      week after device implantation, a 4 x 4 cm field including the implant was
      irradiated with 5,000 rad (200 rad/day x 5 days/week x 5 weeks). The animals were
      maintained for a 6 week period after radiation treatment. After sacrifice, the
      implants were removed, and the tissue capsules studied using conventional
      histologic techniques, including scanning and transmission electron microscopy.
      There was no statistically significant difference in tissue capsule thickness
      compared to nonirradiated controls. Tissue capsule morphology, however, differed
      markedly. Radiation therapy decreased angiogenesis, cellularity, and the
      inflammatory cell response to the implants. Qualitatively, radiation treatment
      seemingly improved rather than compromised the connective tissue response to the
      implants.

PMID- 8555541
TI  - Magnetic field enhancement of antibiotic activity in biofilm forming Pseudomonas
      aeruginosa.
AB  - Device related infection initiated by biofilm bacteria are often difficult to
      resolve with antimicrobial therapy. Study results indicate that application of
      static magnetic fields may enhance the activity of gentamicin against biofilm
      forming Pseudomonas aeruginosa adherent to a polymer substrate. Results indicate
      a maximal reduction of 86.5 +/- 7.2% (n = 6) in the number of adherent viable
      bacteria compared with a control for samples exposed to a 5 gauss (G) magnetic
      field and gentamicin. The effect appears to be limited to magnetic fields between
      5 and 20 G. Experiments using glass, Chronoflex (Polymedica, Golden, CO), Biomer
      (Ethicon, Somerville, NJ), and polystyrene substrate showed that the effect was
      independent of substrate surface. Autoradiograms from In111 uptake experiments
      showed that bacteria colonizing the substrate surface were significantly reduced
      in samples subjected to a magnetic field and gentamicin.

PMID- 8555542
TI  - Chemical modification of implantable biologic tissue for anti-calcification.
AB  - Biologic porcine tissue was modified by coupling sulfonated polyethyl-eneoxide
      (PEO-SO3) and the effect of modification on calcification was evaluated in vitro
      and in vivo. The modification process involves grafting PEO-SO3 to porcine valve
      leaflet either by carbodiimide (EDC) activation or by direct coupling using
      glutaraldehyde. Thermal property, measured by differential scanning calorimetry,
      showed that the shrinkage temperature of modified tissue increased compared with
      control tissue and fresh tissue, suggesting increased thermal stability.
      Resistance to collagenase digestion revealed that modified tissues have greater
      resistance to enzyme digestion than do control tissues. In vitro calcification
      showed that modified tissues have less calcium deposition than do control
      tissues. In vivo calcification, using a rat subcutaneous implantation model, also
      showed less calcification of modified tissue than that of control. The resistance
      of modified tissue to collagenase, higher shrinkage temperature, and reduced
      calcification, when compared with control tissue, attest to the usefulness of
      this chemical modification for implantable biologic tissue.

PMID- 8555543
TI  - Highly oriented, tubular hybrid vascular tissue for a low pressure circulatory
      system.
AB  - A hierarchically structured hybrid vascular tissue was prepared from vascular
      cells and collagen. First a hybrid medial tissue was prepared by pouring a cold
      mixed solution of bovine aortic smooth muscle cells (SMCs) and Type I collagen
      into a tubular glass mold composed of a mandrel and a sheath (inner diameter, 1.5
      mm; outer diameter, 7 mm; length, 7 cm). An SMC incorporating collagenous gel was
      formed with incubation at 37 degrees C. After the sheath of the mold was removed,
      the resulting fragile tissue cultured in the medium shrank in a time dependent
      manner to form an opaque, dense tissue. Seeding at a higher cell density and a
      lower concentration of collagen resulted in rapid and prominent shrinkage.
      Morphologic investigation showed that with time, bipolarly elongated SMCs and
      collagen fiber bundles became positioned around the mandrel. When the mandrel was
      removed, a tubular hybrid medial tissue was formed. A hybrid vascular tissue with
      a hierarchical structure was constructed by seeding endothelial cells onto the
      inner surface of the hybrid medial tissue. Prepared tissues tolerated luminal
      pressures as great as 100 mmHg and mechanical stress applied during the
      anastomotic procedure. This method allowed the authors to prepare hybrid medial
      tissues of predetermined size (specifically inner diameter, wall thickness, and
      length) and mechanical property, which all depend on the mold design, SMC seeding
      density, initial collagen concentration, and incubation period. Hybrid vascular
      tissues may provide physiologic functions such as antithrombogenicity and
      regulation of vasomotor tone when implanted into a venous system.

PMID- 8555544
TI  - An artificial esophagus consisting of cultured human esophageal epithelial cells,
      polyglycolic acid mesh, and collagen.
AB  - Previously, the authors successfully grafted collagen sheets covered with
      cultured human esophageal epithelial cells onto latissimus dorsi muscles of
      athymic mice. To make a tubular artificial esophagus they developed a
      polyglycolic acid mesh-collagen complex tube whose inner side was epithelialized
      in vitro by cultured human esophageal epithelial cells. Human esophageal
      epithelial cells were isolated from normal mucosa resected from specimens of
      esophageal cancer patients and cultured on the surface of the collagen gel in
      which polyglycolic acid mesh was embedded. After the culture reached confluence,
      polyglycolic acid mesh was sutured to create a tubular form lined with cultured
      cell layers (restructured mucosal tube). Such tubes were wrapped in the
      latissimus dorsi muscle flaps of athymic rats using a fibrin glue. The animals
      were killed 4, 8, 20, and 28 days after grafting and the grafted tubes were
      studied histologically. Up to 28 days after grafting, the luminal structure was
      maintained without structure. Eight days after grafting, rat fibroblasts
      infiltrated from the muscle and neovascularization appeared in the collagen
      layer. The grafted epithelium remained healthy and grew to 15 cell layers by 20
      days, much like normal human esophageal epithelium. Staining by anti-laminin
      monoclonal antibody confirmed a basement membrane.

PMID- 8555545
TI  - Continuous monitoring of the spent dialysate urea level using a disposable
      biosensor. Clinical evaluation.
AB  - The first real-time, online measurements obtained using a screen-printed planar
      sensor to continually monitor urea in the spent dialysate are described.
      Evaluation of the sensor performance in the real clinical situation involves an
      extensive comparison of pre and post dialysis characteristics. Steady-state
      response and calibration curves show excellent reproducibility (typically within
      5%; maximum deviation, 15%). The real-time results show that the characteristics
      predicted from the predialysis characterization are preserved during and after
      the prolonged period of continuous contact with the dialysate without needing
      recalibration. An operational stability of more than 10 hours of continuous use
      has been observed. Stability including intermittent wet-storage was found to be
      more than 5 days. Zero-baseline stability greater than 0.2 mmol/l (1.2 Og/dl)
      during the 4 hr treatment period and a resolution of 0.2 mmol/l were achieved,
      with a full-scale range of 15 mmol/l (90 mg/dl). A response time of less than 3
      minutes allows dialysate urea levels to be monitored as a function of dialysis
      parameters such as varying blood flow. Parallel analysis of dialysate samples
      taken at 15 min intervals shows good correlation with the recorded data, although
      correspondence of the absolute values requires that the real-time data be
      rescaled. Because no degradation of the sensor performance was observed in vitro,
      this deviation can be explained only in terms of a dialysate based interference,
      probably caused by changes in pH and buffer.

PMID- 8555546
TI  - A disposable, coated wire heparin sensor.
AB  - The development of an ion-selective electrode heparin sensor consisting of a
      specially formulated polymer membrane doped with tridodecylmethylammonium
      chloride as the heparin complexing agent was recently reported. Because of the
      simple nature of the membrane technology used, the authors envisioned that the
      sensor could be configured as a disposable single-use device for rapid clinical
      or bedside measurement of heparin in a small, discrete sample. To explore this
      possibility, an inexpensive, disposable heparin sensor was created by dip-coating
      a copper wire with the specially formulated heparin-sensing polymeric membrane.
      Coated wire heparin sensors with a broad range of membrane thicknesses, prepared
      by repeatedly dipping the wire in the membrane solution for various times, were
      examined. Data show that increasing the membrane thickness of the sensor to a
      certain degree (more than 10 microns) enhanced the sensor's potentiometric
      response to heparin, although the time required to achieve 90% of the steady
      state potential change was also prolonged. In addition, increasing membrane
      thickness also magnified the stirring effect on the sensor's response. In
      undiluted plasma samples, the coated-wire sensor with an optimized membrane
      thickness yielded a significant (5 to 30 mV) and reproducible response to heparin
      in a clinically relevant concentration range (0.5 to 12 units/ml, respectively).
      The clinical utility of the coated wire heparin sensor was shown using the sensor
      during protamine titration of heparinized plasma to assess the titration end
      point. Preliminary results showed that the titration end-points determined by the
      heparin sensor strongly correlated with those determined by the activated partial
      thromboplastin time clotting assay. The overall time requirement to complete the
      titration process using a set of prefabricated coated wire heparin sensors,
      however, was less than 3 minutes. Further titration studies using undiluted
      clinical whole blood samples are in progress.

PMID- 8555547
TI  - Anti-infection treatment of a transcutaneous device by a collagen-rifampicine
      composite.
AB  - The polyurethane surface of a transcutaneous energy transmitter, which is
      implanted into a subcutaneous pouch for a total artificial heart, was coated with
      a Type I atelocollagen and rifampicine composite to prevent the infection that
      frequently occurs in the interfacial space between the tissue and the device. The
      specimen obtained after 7 weeks from a transcutaneous energy transmitter placed
      in a dorsal subcutaneous pouch of a dog revealed noninfected but well-attached
      dermal tissue without specific epithelial down-growth around the transcutaneous
      energy transmitter surface at the pouch-orifice area. The transcutaneous energy
      transmitter implanted in the pouch adhered well to the subcutaneous tissues. The
      collagen matrix seemed to have provided a favorable environment for the
      regenerating dermal tissue to obstruct the interfacial space. The coated collagen
      antibiotic composite was degraded.

PMID- 8555548
TI  - Experimental study of bioactive polyurethane sponge as an artificial trachea.
AB  - An artificial trachea that has tissue reconstructive activity and elasticity that
      matches a biologic trachea was fabricated using a polyurethane sponge (PS). The
      inner surfaces of the PS were modified by immobilizing collagen, fibronectin, RGD
      peptide, a coating of collagen, and apatite. Two PS pore sizes were prepared, 150
      to 350 microns (small pore) and 350 to 710 microns (large pore). When they were
      implanted in the subcutaneous tissue of rats, study of the implantation showed
      severe inflammatory cell infiltration with the treated PS, especially with
      collagen and collagen coating. Infiltration and maturity of fibroblasts inside
      the PS were noted with fibronectin. Infiltration of inflammatory cells and
      fibroblasts was noted with small pore PS compared with large pore PS. Partial
      tracheal defects were patched with PS. Better epithelization of PS patches was
      observed with fibronectin and apatite compared with the others. The artificial
      trachea made of PS was transplanted into the tracheas of dogs. No separation of
      the anastomosis and tissue reconstruction of the artificial trachea wall were
      observed; however, sputum absorption and tracheal granulation were seen.

PMID- 8555549
TI  - Automatic control of blood volume trends during hemodialysis.
AB  - Dialysis induced hypovolemia plays an important role in triggering intradialytic
      hypotension. The authors developed an automatic system (BVAC) with feedback
      changes in the ultrafiltration rate (UFR) and dialysate conductivity (DC) to
      match blood volume (BV) intradialytic profiles with the desired trajectories. The
      system consists of three subunits: (1) an optical probe to continuously detect
      the BV changes derived from hemoglobin changes, and (2) a dialysis machine
      interfaced with (3), a personal computer in which a time-dependent model is
      implemented. The model is based on a dynamic regulator that can set the actual BV
      changes against the corresponding desired values. Any discrepancy is offset by
      changes in UFR and DC. To verify the efficacy of the BVAC system in reducing
      intradialytic cardiovascular instability, five hypotension-prone patients were
      studied during a three period protocol (A1-B-A2) that lasted six sessions per
      period per patient. During periods A1 and A2, the dialysis procedure was
      conventional hemodialysis (HD) with linear UFR and constant DC. During period B,
      both UFR and DC were automatically regulated by the BVAC system. Mean BV
      reduction and its variability were lower during period B than during periods A1
      and A2 (-10.2%, -11.3%, and -11.5, respectively). Episodes of hypotension were
      significantly (P < 0.05) fewer during period B (n = 1) than during periods A1 (n
      = 8) and A2 (n = 5). The therapeutic interventions defined as infused milliliters
      of isotonic and hypertonic solution were fewer during period B compared with
      periods A1 and A2. Total UF and end-dialysis plasma sodium concentrations did not
      differ in the three study periods. BVAC was effective in improving cardiovascular
      tolerance to treatment.

PMID- 8555550
TI  - Plasma refilling during hemodialysis with decreasing ultrafiltration. Influence
      of dialysate sodium.
AB  - Inadequate plasma refilling is an important determinant of vascular instability
      during hemodialysis. Hypotension is more frequent toward the end of dialysis, as
      the patient reaches dry weight. This study compared plasma volume changes in 12
      patients dialyzed with constant ultrafiltration and a constant dialysate Na of
      140 mEq/L (Group A), sequentially decreasing ultrafiltration (50% in first hour,
      30% in the second hour, and 20% in the third hour) using constant dialysate Na
      (Group B), and sequentially decreasing ultrafiltration with sequentially
      decreasing dialysate Na from 150 to 140 mEq/L (Group C). All of the patients had
      midweek dialysis with each protocol. Blood pressure, hematocrit, blood urea
      nitrogen, serum osmolality, and albumin were determined before and hourly
      thereafter. Ultrafiltration was constant at 12.2 ml/min in Group A but 18.4
      ml/min in the first hour, 11.0 in the second hour, and 7.3 in the third hour in
      Groups B and C. In Group A, plasma volume did not change during the first hour
      but decreased in the second and third hours (4.9%). In Group B, plasma volume
      decreased during the first and second hours 5.6% but slightly increased during
      the third hour 5.3%, whereas in Group C, plasma volume increased during the first
      hour (2.1%), was unchanged during the second hour, and decreased 1.2% during the
      third hour. These data suggest that plasma refilling is enhanced during
      hemodialysis using sequentially decreasing ultrafiltration and high-to-low
      dialysate Na (Group C); this strategy may be preferred to hemodialysis with
      constant dialysate Na and ultrafiltration (Group A) or sequentially decreasing
      ultrafiltration with constant dialysate Na (Group B) when improvement in vascular
      stability is needed.

PMID- 8555551
TI  - Accuracy of an on-line urea monitor compared with urea kinetic model and direct
      dialysis quantification.
AB  - To verify the accuracy of a urea monitor (UM) to assess dialysis adequacy, it was
      compared with a modified direct dialysis quantification method (mDDQ) and with a
      Casino modified urea kinetic model (mUKM) algorithm. Simplified Jindal and
      Daugirdas formulas, an anthropometric body water Watson formula, bioelectric
      impedance analysis, and the Garred model have also been considered. Concerning
      urea removal, UM results are close to mDDQ, as are the predialytic blood urea
      nitrogen values obtained by UM in the initial equilibration test. Urea
      distribution volume results for UM, mDDQ, and bioelectric impedance analysis are
      similar, whereas it appears clearly overestimated by the Watson formula. Urea
      monitor clearances are not significantly different from mDDQ, unlike UM Kt/V,
      which is slightly higher than mDDQ reference value, although with a satisfactory
      degree of concordance. Rebound effect must be considered by sampling after the
      equilibration time (et) when mUKM or simplified Kt/V formulas are used: mUKMet
      Kt/V results are quite similar to mDDQ, as is the Daugirdas value. Regarding
      NPCR, UM results are neither significantly different from mDDQ nor from the
      Garred model, whereas mUKM results are significantly overestimated. When rebound
      is considered, NPCR by mUKMet and NCPR by mDDQ are identical. The UM approach is
      simple and practical, with a satisfactory degree of reliability for clinical
      practice.

PMID- 8555552
TI  - Growth of coagulase negative staphylococci in peritoneal dialysate fluid. Effect
      of calcium concentration.
AB  - The growth of coagulase negative staphylococci (CNS) in spent and unspent
      peritoneal dialysate of physiologic (1.25 mmol/l) and standard (1.62 mmol/l)
      [Ca2++] was studied. Dialysate was prepared by filter sterilization and pH and
      iCa were measured. Three isolates of CNS grown in unsupplemented Mueller Hinton
      broth for 18 to 20 hr at 37 degrees C were adjusted to a density of 1.5 x 10(8)
      CFU/ml. The dialysate (5.4 ml) was inoculated with 0.6 ml of a 10(-4) dilution
      and then incubated aerobically at 35 degrees C. Plates were made at 0, 6, and 24
      hr, and CFU/100 microliters were counted after 24 hr. In a larger study, 10
      isolates of CNS were examined. Coagulase negative staphylococcal growth was
      inhibited by unspent dialysate (P = 0.000; unpaired t-test). Growth was greater
      in spent physiologic [Ca++] dialysate (iCa -0.76 mmol/l) at 6 hr (P = 0.007) and
      at 24 hr (P = 0.000) than in standard dialysate (iCa = 0.86 mmol/l) for two of
      three strains in the pilot study. Similar findings were noted for 4 of 8 strains
      in the larger study. There was an overall trend for greater growth in physiologic
      [Ca++] dialysate (P = 0.09). Some strains of CNS grow better in lower [Ca++]
      dialysate, perhaps representing clinically relevant trophism.

PMID- 8555553
TI  - Persistent inhibition of neutrophil function by glucose based dialysis solutions.
AB  - Local defense mechanisms play an important role in prevention of peritonitis, a
      major complication of continuous ambulatory peritoneal dialysis (CAPD) therapy.
      The authors have shown that hypertonic, lactate containing glucose based dialysis
      solutions (GBDS) used in CAPD lead to an immediate and complete pH-dependent
      inhibition of actin polymerization and phagocytosis in polymorphonuclear
      neutrophils (PMN) in vitro. Earlier studies have shown that the pH of the fluid
      equilibrates from 5.2 to approximately 6.4 during the first 30 min of
      intraperitoneal dwell time. Thus, the authors designed the current study to
      determine whether the inhibition of cytoskeletal function and intracellular
      acidosis induced by acidic solutions are reversed by this pH adjustment. To this
      end, actin polymerization, phagocytosis, and intracellular pH were studied in PMN
      isolated from healthy human donors during a 10 min incubation in commercially
      available GBDS at pH 5.2 and again after pH adjustment to 6.4. Actin
      polymerization was assessed by measuring F-actin content using NBD phallacidin
      staining and fluorescence activated cell scanner analysis. Phagocytosis was
      assessed using zymosan particles, and intracellular pH was monitored by
      spectrofluorometry. The impairment of cytoskeletal alterations in cells exposed
      to GBDS at pH 5.2 was persistent and not fully reversed by adjusting the pH.
      Likewise, phagocytosis remained markedly inhibited and intracellular pH did not
      rise after adjustment of pH. Thus, the results demonstrate a persistent cytotoxic
      effect of CAPD solutions on human phagocytes. The authors think that CAPD
      solutions must be modified to provide a more physiologic pH environment for
      proper phagocyte function.

PMID- 8555554
TI  - Influence of rapid correction of metabolic acidosis on serum osteocalcin level in
      chronic renal failure.
AB  - Metabolic acidosis induces a combination of inhibited osteoblastic and stimulated
      osteoclastic activity. To determine the role of alkali therapy in osteoblast
      function in chronic renal failure, serum bone isoenzyme of alkaline phosphatase
      (BAP) and osteocalcin were assessed before and after bicarbonate infusion.
      Eighteen patients with mild to moderate metabolic acidosis, none of whom had
      received dialysis therapy, were enrolled in this study. Metabolic acidosis was
      corrected by continuous bicarbonate infusion while plasma ionized calcium was
      monitored at 5 min intervals and held at the preinfusion level by calcium
      solution infusion during the entire procedure. The end-point of the study was
      reached when the plasma bicarbonate was approximately 24 mmol/l or pH was
      approximately 7.4 and plasma ionized calcium was clamped at the preinfusion level
      with only a 0.01 mmol/l fluctuation. The plasma pH (7.31 +/- 0.04 vs. 7.40 +/-
      0.03, P < 0.001), bicarbonate (18.46 +/- 2.49 vs. 23.66 +/- 2.72 mmol/l, P <
      0.001), serum total calcium, and osteocalcin (15.61 +/- 6.45 vs. 18.79 +/- 6.71
      mg/l, P < 0.05) levels were significantly increased, whereas serum concentrations
      of alkaline phosphatase and albumin levels were significantly decreased after
      bicarbonate infusion. The serum BAP (1.85 +/- 1.29 vs. 1.79 +/- 1.18 mukat/l, P =
      0.252), and inorganic phosphorus levels showed no significant differences before
      and after bicarbonate infusion. These results demonstrate that rapid correction
      of metabolic acidosis improves osteoblast function and may underline the
      importance of maintaining normal acid-base homeostasis in chronic renal failure.

PMID- 8555555
TI  - Clinical studies on molybdenum in patients requiring long-term hemodialysis.
AB  - Molybdenum is an essential trace element in humans. However, the serum molybdenum
      level or its role in patients with chronic renal failure or those requiring long
      term hemodialysis remains unknown. The authors examined the serum molybdenum
      levels and studied the role of hemodialysis in 60 patients requiring long-term
      hemodialysis. The serum molybdenum levels of the 60 patients with chronic renal
      failure were examined before and after hemodialysis. The authors also studied the
      relationships between serum molybdenum levels and beta 2-microglobulin (beta 2
      MG) levels, c-parathyroid hormone (C-PTH) levels, and dialysis related arthritis
      in the 60 patients. Molybdenum was measured with a flameless atomic absorption
      spectrophotometer equipped with an autobackground corrector. The level of
      molybdenum in serum significantly (P < 0.01) decreased from 2.7 +/- 1.9
      micrograms/dl (normal value, 0.02-0.13 micrograms/dl) before hemodialysis to 1.4
      +/- 0.7 micrograms/dl after hemodialysis. The correlation between serum
      molybdenum value and serum beta 2-MG level was significant (P < 0.01). The
      authors also found significant correlations between serum molybdenum level and C
      PTH value, serum calcium ion (C++) level in serum, and duration of hemodialysis.
      Serum molybdenum levels were high (12.8 +/- 0.96 micrograms/dl) in nine patients
      with dialysis related arthritis. In conclusion, serum molybdenum levels are high
      in patients undergoing long-term hemodialysis, and abnormal molybdenum
      accumulation may contribute to dialysis related arthritis.

PMID- 8555556
TI  - Hepatitis C virus RNA in patients with anti-HCV on hemodialysis. Relationship to
      transaminase levels.
AB  - This study was performed in patients with hepatitis C virus (HCV) who were
      treated with hemodialysis to determine the relationships among alanine amino
      transferase (ALT) levels, immunoglobulin (Ig) G anti-HCV, IgM anti-HCV core, and
      HCV RNA. Of 107 patients on hemodialysis, 27 had positive IgG anti-HCV. Eight of
      the patients who had HCV were evaluated every 8 months during a period of 2
      years, using the following selection criteria: positive IgG against c-22, c33-c,
      5-1-1, and c100-3 viral peptides; absence of infection by hepatitis A virus,
      hepatitis B virus, cytomegalo-virus, Epstein-Barr virus, herpes simplex virus,
      and human immunodeficiency virus, as well as absence of hepatotoxic drugs or
      cholelithiasis. We considered elevated ALT values as those more than 150% of the
      upper limit of normal. Three of the patients had persistent elevation of ALT
      levels, two had alternating elevation of ALT levels, and three had normal ALT
      levels in all blood samples. Of the 24 blood samples, 11 had elevation of ALT
      (45.8%) levels that showed positive IgM anti-HCV, but only 7 of these 11 had
      positive HCV RNA (63.6%). None of the 13 blood samples without elevation of ALT
      had positive IgM anti-HCV, but 5 had positive HCV RNA (38.5%). We found an
      excellent correlation between IgM anti-HCV and ALT levels (r = 0.81). There was
      no statistically significant difference between the mean ALT values on the 12
      blood samples that had positive HCV RNA and the mean ALT values of the negative
      HCV RNA samples (53.5 +/- 28.0 IU/l vs. 37.4 +/- 17.5 IU/l, respectively). IgM
      anti-HCV is related to the elevation of ALT levels and can be used as a serologic
      marker to indicate the presence of active HCV induced liver damage. Serum ALT
      levels do not correlate with the detection of viral genome in sera. IgG anti-HCV
      is not necessarily associated with HCV RNA or IgM anti-HCV. The absence of IgM
      and HCV RNA in patients with IgG anti-HCV and normal ALT levels does not
      necessarily suggest the absence of active HCV infection.

PMID- 8555557
TI  - Influence of longer term left ventricular assist device support on valvular
      regurgitation.
AB  - The authors previously published data that describe acute alterations in
      ventricular dimensions and in the severity of mitral and tricuspid regurgitation
      (MR/TR) after initiation of left ventricular assist device (LVAD) pumping. In the
      current study, measurements of ventricular size and regurgitant jet area acquired
      after LVAD implantation are presented. Eight patients had LVAD implanted pending
      cardiac transplantation (duration of assist 70-279 days; mean, 162 +/- 29 days).
      Echocardiograms were obtained at the time of LVAD implant and later during LVAD
      support (mean time for late echo, 95 +/- 32 days post-implant). Comparisons of
      pre-implant with late post-implant data showed: increased TR jet area (4.8 +/-
      1.0 cm2 vs. 8.0 +/- 1.7 cm2 P < 0.05); increased right ventricular (RV) end
      systolic dimension (31 +/- 4 vs 40 +/- 5 mm, P < 0.05); and increased RV end
      diastolic dimension (35 +/- 4 vs. 45 +/- 5 mm, P < 0.065). Decreased MR jet area
      and decreased LV dimensions (P < 0.05) also were noted on comparison of pre
      implant and late post-implant data. There were no significant differences between
      any immediate post-implant and late post-implant echocardiographic measurements.
      No patient had clinical evidence of RV failure. LV mechanical assist causes an
      acute increase in TR, presumably by volume loading the RV. TR and RV enlargement
      persisted but did not discernibly worsen on subsequent post-implant
      echocardiograms. LV dimensions and MR remained less than the pre-implant values
      on later post-implant determinations.

PMID- 8555558
TI  - The BVS 5000 biventricular assist device. The worldwide registry experience.
AB  - The BVS 5000 is an extracorporeal pulsatile assist device for temporary
      univentricular or biventricular support. A registry of BVS 5000 usage has
      enrolled 420 patients between June 1987 and February 1994. Data were voluntarily
      contributed from more than 60 centers in 15 countries. The device has been
      implanted for post-cardiotomy shock (n = 211), cardiomyopathy (n = 94), acute
      myocardial infarction (AMI) shock (n = 44), failed transplant (n = 45), and other
      indications (n = 26). Device support was biventricular in 65% of patients, left
      in 29%, and right in 5%. Mean length of support was 5.2 days. Of the patients,
      78% were men and 81% were 60 years of age or younger. In the post-cardiotomy
      group, 116 (55%) were weaned or bridged, and 27% were discharged. Seventy percent
      of cardiomyopathy patients went on to transplant, of which 39 (58%) were
      discharged. Of the patients with AMI shock, 52% underwent transplant, and 16
      (70%) of these were discharged. The use of ventricular support in the setting of
      post-cardiotomy is explored and compared with the standard practice of supporting
      patients with inotropes and intra-aortic balloon pumps (IABP). Analysis of the
      poor outcomes and high cost of standard practice suggests that ventricular assist
      may positively affect outcomes in this population. This multi-institutional
      experience supports the use of the BVS 5000 for short-term ventricular assistance
      and suggests the need for additional study of ventricular support in the post
      cardiotomy setting.

PMID- 8555559
TI  - Initial clinical experience with a wearable controller for the Novacor left
      ventricular assist system.
AB  - The Novacor left ventricular assist system (LVAS), an implanted
      electromechanically driven blood pump, has been used in an ongoing clinical trial
      as a bridge to cardiac transplantation since 1984. The initial configuration
      included a console based extracorporeal controller. Because patients supported by
      the device usually become rehabilitated and highly mobile, a wearable control
      system was developed for the ambulatory patient. Ergonomically designed for
      portability, comfort, and appearance, it offers the recipient greater mobility,
      improved self-image, and an enhanced quality of life. This wearable control
      system consists of a microprocessor based compact controller that drives the
      implanted pump/drive unit in synchronous counterpulsation to the native heart.
      Main and reserve rechargeable power packs, each incorporating a "smart"
      monitoring circuit with charge-level display and alarm, are capable of supporting
      the pump for as long as 7 hr. An LVAS monitor can be connected to the controller
      for device monitoring and adjustment or as a power supply in lieu of the main
      power pack. Clinical evaluation in patients with end-stage heart disease followed
      the same protocol as the console study. By April 4, 1994, 41 patients had been
      supported by the wearable system, including 9 patients currently being supported.
      Mean duration of use was 51 days (range, 1.5-143+ days), compared with 42 days
      for 170 console patients (range, 0-370 days). Survival to transplant was 66%,
      which was similar to the survival (60%) for the patients using the console. Post
      transplant survival was 100%, compared with 90% for console patients (not
      significantly different). After recovering from implant surgery and pre-implant
      morbidity, device recipients had considerable freedom and mobility and were able
      to move freely within and outside the hospital. Recipients could readily switch
      between monitored and untethered operation and could manage power pack
      replacement and recharging.

PMID- 8555560
TI  - Use of a left ventricular assist device in an outpatient setting.
AB  - The vented electric Heartmate LVAD (VE-LVAD) (Thermo Cardiosystems, Inc., Woburn,
      MA) is a reliable, fully portable system that allows selected patients with end
      stage cardiomyopathy to undergo outpatient treatment while waiting for heart
      transplantation. This implantable, pusher-plate LVAD is actuated by an electric
      motor located within the pump housing. The patient wears external batteries and a
      system controller, which power and control the LVAD motor through a percutaneous
      lead. Since May 1991, four men have been supported with the VE-LVAD. They ranged
      in age from 33 to 50 years (mean, 44.3 years); two had idiopathic cardiomyopathy,
      and two had ischemic cardiomyopathy. Of the four patients, three underwent
      support of 196, 219, and 504 days; support in the fourth patient is ongoing at
      more than 90 days. All four patients were fully rehabilitated to New York Heart
      Association Class I status. Because they were well and fully mobile, the protocol
      was amended to allow these patients to leave the hospital in a four phase program
      that begins with 16 hr day passes and leads to hospital discharge. When patients
      leave the hospital, they are accompanied by trained family members or friends.
      The patients who have participated in the program have performed routine
      activities, attended social events, and spent the night at home. The VE-LVAD
      system seems safe and appropriate for the outpatient setting in selected
      patients. Patients have been able to manage the system without assistance from
      medical or engineering personnel. This initial positive experience with
      outpatient LVAD treatment demonstrates the potential for providing long-term
      cardiac support with this type of implantable technology.

PMID- 8555561
TI  - Mechanical circulatory support and heart transplantation. Pre-operative status
      and outcome.
AB  - Between July 1988 and December 1993, 118 patients waiting for heart
      transplantation underwent mechanical circulatory support by an extracorporeal,
      pneumatically driven assist device (the Berlin Heart System) to maintain a
      sufficient circulation and to restore impaired organ function (109 patients
      requiring a biventricular assist device [BVAD], 9 patients requiring a left
      ventricular assist device [LVAD]). Before implantation, all patients were in
      severe cardiogenic shock, despite maximum inotropic support; all had end organ
      failure. The aim of a retrospective study in 70 patients (for whom pre-operative
      parameters were available) was to identify patients who would permit from this
      procedure and could undergo successful transplantation. After a mean bridging
      time of 34.8 days, 75 (63.5%) patients underwent transplant, and 52 (44.1%) were
      discharged. Pre-operative coagulation parameters (fibrinogen, antithrombin III,
      platelet count, and kinetics) were correlated to post-operative blood loss and
      outcome. Patients who had no or mild coagulation disorders because of a shorter
      phase of low cardiac output before implantation of the assist device proved to
      gain faster restitution of organ function and most underwent transplantation. As
      a result of these observations, implantation of an assist device before shock
      induced coagulopathy could occur allowed a greater number of patients to undergo
      successful bridging and be discharged after heart transplantation.

PMID- 8555562
TI  - Development and clinical application of a next generation implantable
      echocardiography probe for monitoring cardiac function under assisted circulation
      after open heart surgery.
AB  - Post-operative cardiac function generally is monitored by electrocardiography,
      invasive measurement of blood pressure, and determination of hemodynamic
      variables, such as pulmonary pressures and cardiac output with a Swan-Ganz
      catheter. In recent years, transesophageal echocardiography has been introduced
      into clinical use, but it is not a popular method of monitoring for various
      reasons, including the difficulty of application to unconscious post-operative
      patients. Since 1991, we have been developing a small implantable
      echocardiography probe. This probe was tested in 15 patients who underwent open
      heart surgery for severe left ventricular hypofunction, and its clinical utility
      was demonstrated. No deaths occurred in this series. The implantable
      echocardiography probe allowed post-operative cardiac function to be monitored in
      real-time. The ejection fraction, the cardiac output, the status of valves after
      valvuloplasty, the presence of cardiac tamponade, and other variables could be
      assessed. The echocardiography probe can be positioned at any site where specific
      information is desired during surgery. It can be inserted as easily as a
      pericardial drain tube and is removed in the same manner when no longer
      necessary. This probe has the potential to be useful for monitoring patients on
      assisted circulation after cardiac surgery.

PMID- 8555563
TI  - Assessment of a percutaneous Hemopump in high risk coronary angioplasty patients.
AB  - This study assessed the safety and efficacy of a new 14 Fr Hemopump device. Ten
      high risk patients requiring percutaneous transluminal coronary angioplasty
      (PTCA) (last remaining patent vessel or low left ventricular ejection fraction)
      underwent PTCA with the prophylactic use of the Hemopump. This device was
      inserted percutaneously through the femoral artery using a 16 Fr sheath and
      placed into the left ventricle. Hemodynamic parameters (pulmonary capillary wedge
      pressure, cardiac output, mean aortic pressure) were recorded before, during, and
      after PTCA when the Hemopump was on and off. Adequate placement of the Hemopump
      was obtained in all patients with moderate temporary rhythm instability, and PTCA
      was performed in all patients. Under assist, pulmonary capillary wedge pressure
      was 22 +/- 8 mmHg, compared with 29 +/- 7 mmHg (P < 0.05), whereas no significant
      change in other hemodynamic parameters was observed. One patient experienced
      ventricular fibrillation twice during PTCA, which was correlated by electrical
      cardioversion. During this temporary cardiac arrest, the aortic blood pressure
      was maintained at 50 mmHg with the Hemopump. For all patients, the Hemopump was
      withdrawn 15 min after the end of PTCA, and the sheath was removed 4-6 hr later.
      However, two patients required surgical sheath removal. One patient died of
      cardiogenic shock in the intensive care unit. Other patients were discharged 3
      days after the procedure. Long-term follow-up shows eight surviving patients.
      These data show that 1) the 14 Fr percutaneous Hemopump is safe, and 2) can
      unload the left ventricle during PTCA while maintaining mean aortic pressure and
      cardiac output.

PMID- 8555564
TI  - Chronic in vivo evaluation of an electrohydraulic total artificial heart.
AB  - Development of the Abiomed total artificial heart (TAH) designed for human use is
      progressing. Implant durations of longer than 60 days have been achieved in
      calves. The device consists of blood pumps, valves, and a hydraulic atrial flow
      balancing chamber fabricated from polyetherurethane. The energy converter, a
      centrifugal hydraulic pump with a rotary fluid switching valve, is positioned
      between the blood pumps. In two consecutive chronic in vivo studies (47 days and
      longer than 60 days), cardiac output was maintained in excess of 8 l/min. The
      atrial flow balancing chamber maintained a mean right-to-left pressure gradient
      of 7.5 and -1.4 mmHg in each respective study. There were no pulmonary
      complications. Platelet counts, fibrinogen concentrations, and hematocrit values
      returned to baseline levels within 20 days, whereas bilirubin, serum glutamic
      oxaloacetic transaminase, blood urea nitrogen, and creatinine levels returned to
      normal within 1 week of implant. After the first post-operative day, plasma free
      hemoglobin levels of less than 10 mg/dl indicated no device-related hemolysis
      throughout the duration of the studies. At explant (47 day study), pathologic
      analysis showed no renal infarcts, no tissue necrosis, and no thermal damage. The
      device was fully encapsulated by 2-4 mm thick fibrous connective tissue. A newly
      designed textured-to-smooth surface inflow showed no signs of pannus ingrowth or
      thrombotic complications. These studies demonstrate that this TAH is suitable for
      long-term implantation.

PMID- 8555565
TI  - Progress in Cleveland Clinic-Nimbus total artificial heart development.
AB  - A totally implantable, Cleveland Clinic-Nimbus total artificial heart (TAH) uses
      electrohydraulic energy conversion and an automatic left master-alternate mode
      control scheme, with a filling sensitivity of 1.0 l/min/mmHg and a maximum output
      of 9.5 l/min. The TAHs were tested in 12 calves for 1-120 days with normal major
      organ and blood cell function. Post-operative suppression of platelet aggregation
      recovered by the second post-operative week. The gelatin-coated pump surface
      generally was clean without any anticoagulants and free from infection. Embolism,
      which occurred in two cases, was caused by complications attributable to fungal
      infection in a Dacron graft and by thrombus formed around a jugular vein
      catheter. A system with a hybridized microcircuit controller in the
      interventricular space has been tested successfully in the three most recent
      cases, with a peak device surface temperature elevation of 6.5 degrees C. Heat
      effects were confined to the tissues immediately adjacent to the hottest spots.
      The carbon fiber-reinforced epoxy housing and 60 ml butyl rubber compliance
      chamber showed good tissue compatibility with a thin, fibrous tissue capsule. The
      transcutaneous energy transmission system and the internal battery functioned
      well as designed in the most recent animal implant.

PMID- 8555566
TI  - The Baylor total artificial heart. Flow visualization studies.
AB  - To analyze the flow patterns of the left blood chamber of the Baylor total
      artificial heart (TAH) and to evaluate influences of the inflow valve angle to
      the flow patterns, flow visualization studies were performed. The inflow valve
      angle of the left housing was changed by 20 degrees orthogonal to the inflow
      tube, and comparison studies of the modified and unmodified models were made. For
      evaluating sectional flow patterns, a laser light was used, the clear transparent
      housing was scanned segmentally, and flow patterns were recorded on high contrast
      film for measuring flow velocities. A signal was used that synchronized the
      timing of the camera shutter to the pusher-plate movement signal. With the
      modified 20 degree inflow valve direction, there were better closing
      characteristics of the inflow valve leaflets. At the same time, we could
      successfully reduce the vortex formation at the inflow port, which may cause
      thrombus formation. We also have improved the washout during the diastolic phase
      in not only the bottom area, but in the entire pumping chamber. This flow
      visualization setup is simple and inexpensive. It is useful not only for
      validation of global flow patterns, but also for validation of local flow
      velocities of various blood pumps.

PMID- 8555567
TI  - Can total artificial heart animals control their TAH by themselves? One year
      survival of a TAH goat using a new automatic control method (1/R control).
AB  - A total artificial heart (TAH) goat survived for 360 days on the new automatic
      control method (1/R control), in which the cardiac output of the TAH can be
      controlled through the cardiovascular center by making it function by reflecting
      the beta-adrenergic reaction in peripheral vascular resistance. This is thought
      to be the only long-term, real-time, measurable parameter by which information on
      the activity of the cardiovascular center can be received directly by the TAH
      system. In this goat, the hemodynamic parameters (RAP, AoP, and so forth) were
      kept within physiologic limits when control was stable, and the cardiac output
      was automatically increased in response to exercise, not unlike that in the
      natural heart. There were no abnormal blood chemical or hormone data except at
      end stage. Based on these results 1/R can be considered a physiologic control
      method for a TAH.

PMID- 8555568
TI  - Oxygen metabolism in animals with total artificial hearts.
AB  - The relationship between indices of oxygen metabolism has been widely used in
      clinical practice to evaluate the adequacy of tissue perfusion, to predict the
      outcome of the critically ill patient, and to evaluate the effectiveness of
      therapies. This study quantitated and correlated the relationship between oxygen
      delivery (DO2), oxygen consumption (VO2), and oxygen extraction rate (EO2) in 14
      animals with total artificial hearts (TAH) to investigate the oxygen metabolism
      in animals with TAH during different physiologic and pathologic conditions. These
      14 animals were subdivided into healthy, critical, and exercise groups. There was
      a physiologic dependence of DO2 to VO2 in animals in the healthy and exercise
      groups, whereas a pathologic dependence of VO2 to DO2 appeared to occur in
      animals in the critical group. Reduced or inadequate VO2 leads to organ
      dysfunction, shock syndrome, multiple organ failure, and finally, mortality.
      Providing a higher level of DO2 by restoring circulating blood volume, increasing
      cardiac output, raising hematocrit levels, and improving pulmonary function to
      achieve a higher level of oxygen extract efficiency and oxygen consumption in
      animals with TAH that are in a critical condition might be helpful for the
      treatment of complications and result in decreasing mortality. Using the
      relationship between indices of oxygen metabolism as a physiologic modifier for
      TAH control algorithms also might improve the physiologic performance and quality
      of life of TAH recipients.

PMID- 8555570
TI  - A pumping artificial lung.
AB  - The authors have developed a single device that performs the functions of a
      centrifugal pump and a membrane artificial lung. Unlike other systems that
      combine pre-existing components, our device is constructed so that the vanes of
      an impeller pump are made up of gas exchanging microporous fibers. The device has
      a variety of applications: in an easily primed emergency cardiopulmonary bypass
      circuit, as a low surface area component of extracorporeal life support (ECLS)
      circuits, and as a low volume, high perfusion rate bridge to transplant. Five
      prototype devices, with gas exchange surface areas ranging from 0.09 to 0.35 m2,
      have been tested in vitro to characterize the gas exchange and pumping
      capabilities of the device. These small devices pump fluid effectively. The
      larger device could pump 2.7 l/min with 91 mmHg pressure difference from inlet to
      outlet. These preliminary devices transferred to only 33 ml/min of oxygen (O2)
      and 35 ml/min of carbon dioxide (CO2), however. The combination of pumping
      ability and gas exchange is encouraging, but it is apparent that larger surface
      areas and less blood shunting around the gas exchanging impellers are needed for
      sufficient gas exchange. Somewhat higher surface areas are feasible within the
      pump-head casing used for these preliminary prototypes; larger casings could be
      used for still higher surface areas.

PMID- 8555569
TI  - Adaptation of tissue to a chronic heat load.
AB  - Determination of the chronic effect of heat on tissue is one of the important
      issues facing mechanically actuated total artificial heart (TAH) development. In
      an effort to characterize this effect, implantations of heating devices producing
      constant heat fluxes of 0.04 watts/cm2, 0.06 W/cm2, and 0.08 W/cm2 were performed
      in 11 calves (H-series). Heated disks were implanted adjacent to lung and muscle
      tissue for a period of 7 weeks. Temperature sensors were placed at the surface as
      part of the heater assemblies. The results showed that initially, temperature
      elevations above body temperature (delta T) were 6.4 +/- 0.6 degrees C, 4.5 +/-
      0.2 degrees C, and 1.8 +/- 0.5 degrees C at the muscle heater surface for 0.08,
      0.06, and 0.04 W/cm2, respectively. At 2 weeks after implant delta T values
      changed to 5.5 +/- 0.6 degrees C, 3.4 +/- 0.2 degrees C, and 1.8 +/- 0.2 degrees
      C, respectively. Seven weeks after implant, delta T values decreased to 3.7 +/-
      1.2 degrees C, 2.8 +/- 0.1 degrees C, and 0.8 degrees C for 0.08, 0.06, and 0.04
      W/cm2, respectively. The authors think this change is attributable to an adaptive
      response of the tissue to increase heat dissipation through angiogenesis. Results
      from three TAH cases indicated that at two measured tissue interfaces, delta T
      decreased by 1 degrees C during a 15 day period. At the same time, the waste heat
      (volts x current in-flow x afterload to the blood) remained constant at 11.1 +/-
      0.5 W during this period. This decrease in delta T corresponded to that observed
      for the H-series experiments at the higher heat fluxes. Thus, it appears that
      adaptation observed in the H-series experiments also is seen for tissues
      surrounding heat sources such as the TAH.

PMID- 8555571
TI  - Design and evaluation of a new, low pressure loss, implantable artificial lung.
AB  - The authors designed and tested an artificial lung intended for intrathoracic
      implantation as a bridge to lung transplantation in chronic pulmonary
      insufficiency or as an alternative in the treatment of advanced acute respiratory
      failure. The prototype devices are comprised of 380 microns outer diameter
      polypropylene matted fibers with a blood path length of 3.5 cm, frontal area of
      128 cm2, void fraction (porosity) of 0.53, and surface area of approximately 2.2
      m2. Blood flow is external and approximately perpendicular to the fiber bundle,
      which fits in an extruded, flexible polyethylene terephthalate housing. Inflow
      and outflow anastomoses are made to the pulmonary artery and the left atrium,
      respectively, thereby avoiding a prosthetic blood pump. Inlet and outlet gas
      lines exit through the chest wall. Nine in vitro experiments of oxygen (O2)
      transfer performance by the device, with water, initially were done. Our
      previously described semiempirical mathematical model of convective O2 transfer
      in cross-flow, hollow fiber membrane lungs was applied to the results from the
      water tests to predict the transfer rates at any set of blood conditions. Five in
      vitro blood tests were conducted using a single-pass technique to evaluate O2 and
      carbon dioxide (CO2) transfer rates, measure pressure losses, and compare
      predicted and measured O2 transfer rates. O2 transfer rates of 150-200 ml/min,
      and CO2 transfer rates exceeding 200 ml/min, could be achieved at blood flow
      rates as great as 4 l/min. Pressure drops of approximately 10-20 mmHg were
      observed at blood flow rates of 2-4 l/min. Preliminary results of device
      implantation in two pigs indicate the feasibility of achieving clinically
      significant O2 and CO2 transfer rates with a low blood-side pressure loss.

PMID- 8555572
TI  - Improved gas exchange performance of the intravascular oxygenator by active blood
      mixing.
AB  - The intravascular oxygenator and carbon dioxide removal device (IVOX;
      CardioPulmonics, Salt Lake City, UT) has been shown to perform 30% of the gas
      exchange in animals and patients with acute respiratory failure. Among the
      factors that limit gas exchange is the mass transfer resistance in the blood
      phase. To determine if a reduction in mass transfer resistance by mixing venous
      blood can enhance the O2 transfer and CO2 removal by IVOX, a right atrium
      pulmonary artery venovenous bypass circuit was used in sheep to model the adult
      vena cava. A size 9 IVOX (894 fibers with 0.41 m2 surface area, n = 5) was
      incorporated in the bypass circuit and the blood flow controlled by a roller pump
      ranging from 1 to 4 l/min. An intra-aortic balloon was placed near the shaft of
      the IVOX and pulsated at the rate adjusted to best improve CO2 removal (100-120
      bpm). O2 transfer and CO2 removal were measured with balloon pulsation on and off
      at different flow rates. Results showed that blood mixing by pulsation of the
      balloon caused a 25-49% increase in O2 transfer by IVOX, and this increase
      remained relatively constant throughout the full flow range. CO2 removal was also
      increased by up to 35%, but at flows between 3.5 and 4 l/min, the effect of
      mixing was diminished. It is concluded that reduction in the mass transfer
      resistance by blood mixing improves gas exchange. Because O2 is more diffusion
      limited, it is more dependent upon mixing of blood for gas exchange than CO2.
      More design improvements to incorporate active mixing may further enhance the gas
      exchange performance of IVOX.

PMID- 8555573
TI  - Small intrapulmonary artery lung prototypes: design, construction, and in vitro
      water testing.
AB  - Blind-ended, hollow fibers mounted on a pulmonary artery catheter may allow O2
      and CO2 transfer in the vena cava, right ventricle, and pulmonary artery. The
      effects of fiber length, manifold number, and gas oscillation on mass and
      momentum transfer with water perfusate using mass spectrometry and mass flow
      controllers were studied. Manifolds with 112-196 microporous polypropylene fibers
      were mounted on 8 Fr multiple lumen, commercially available pulmonary artery
      catheters. Fiber lengths varied from 0.5 to 16 cm and surface areas from 7 to 220
      cm2. Prototypes with 2 cm long fibers were constructed with 1-15 manifolds. A two
      manifold prototype with 8 cm long fibers and a surface area of 378 cm2 was also
      studied. The transfer failed to scale with manifold number because the steady gas
      flow was maldistributed to the manifolds. Oscillating gas pressures from 780 to
      76 mmHg absolute at a rate of 40 cycles/min increased CO2 transfer up to 15-fold
      and O2 transfer up to 2.5-fold. Oscillation also corrected the maldistribution.
      Optimal fiber lengths of 3 and 1 cm for O2 and CO2, respectively, were seen with
      steady gas flow, and 8 cm for both with oscillatory gas flow.

PMID- 8555574
TI  - Results of the unidirectional Centri-Safe arterial valve for prevention of
      retrograde flow during cardiopulmonary bypass.
AB  - Retrograde blood from the aortic cannula into the cardiopulmonary circuit may
      lead to aortic air emboli when nonocclusive centrifugal pumps are used. The
      authors tested a nonregurgitant, unidirectional valve containing a Teflon ball
      occluder to prevent backflow. In vitro measurements of leakage rate, forward flow
      pressure drop, burst strength, and hemolysis levels along with animal (n = 12)
      and human (n = 12) in vivo hematologic and hemolysis levels were measured. Data
      were analyzed by paired and unpaired Student's t-test. Pressure drop differences
      at flows of 5 l/min were 7.3 +/- 0.3 mmHg before and 7.6 +/- 0.1 mmHg after
      10,800 cycles of pulsatile pumping. (P = NS). Leakage rate during this period at
      pressures of 100 mmHg was not significant. Volume required to close the Teflon
      ball was less than 1 ml. Hemolysis analysis done in vitro and in vivo in control
      (no valve) and experimental (valve) groups used hemoglobin, hematocrit,
      platelets, plasma free hemoglobin, and lactic dehydrogenase as hemolysis indices.
      There were no statistical differences. The authors conclude that the CentriSafe
      valve (Cardiac Systems, Inc., Conshohocken, PA) is safe and prevents fatal
      backflow and air emboli. The valve is nonthrombotic in anticoagulated blood, can
      be opened and closed thousands of times, and has a burst strength equal to or
      greater than other components in the perfusion setup.

PMID- 8555575
TI  - Neutrophil dynamics and retention in lung, oxygenator, and arterial filter during
      cardiopulmonary bypass in a pig model.
AB  - Interactions of neutrophils with adsorbed proteins in components of the
      cardiopulmonary bypass (CPB) circuit and expression of leukocyte adhesion
      molecules on activated neutrophils affect neutrophil kinetics and margination.
      Lung and skeletal muscle along with oxygenator (OX) and arterial filter (AF) in
      the extracorporeal circuit provide the major areas of neutrophil (N) interaction.
      The dynamics of N-interaction and N-retention during 3 hr CPB was quantified with
      autologous In-111 labeled neutrophils (INN) in 4 groups of 20 Yorkshire pigs (28
      35 kg, 5 sham; 5 CPB, 1 hr; 5 CPB, 3 hr and 5 CPB with heparinized circuit, 3
      hr); anesthetized pigs were injected with INN (500-650 microCi), 30 min before
      CPB and heparinized, and underwent CPB with a roller pump, a hollow fiber OX
      (Bentley CM 50, 5.0 m2) and AF (Bentley AF 025, 0.25 m2) at 2.5-3.6 l/min for 3
      hr. N-dynamics on OX and AF was monitored by a calibrated Geiger probe.
      Neutrophil deposition, like that of plasma proteins on OX, reached a steady state
      almost instantly, but increased on filter with CPB time. INN distribution was
      viewed with a gamma camera; total INN was measured with an ion chamber and INN in
      samples of fibers and tissues was quantified with a gamma counter. INN in lung
      did not change significantly during CPB and increased in liver. The percentage of
      injected INN in lung, liver, and brain changed with CPB time and showed
      significant increase over sham-operated animals. Heparin coating of components
      decreased INN retention. INN/meter2 of lung, OX, and AF at 3 hr were 0.26 +/-
      0.07%, 0.06 +/- 0.02%, and 6.17 +/- 3.94%, and significantly lower on a heparin
      coated filter (2.14 +/- 1.30%). Capillary surface areas of viscera and connective
      tissues (lung, 100; liver, 134; spleen, 20; heart, 7; skeletal muscle, 92; fat,
      12; bone, 3; bone marrow, 5; brain, 0.1 meter2) were estimated from distribution
      of activated INN in pigs. Lung INN retention was much higher than that of the
      polymer surfaces of OX/AF, indicating the role of cell adhesion molecules on INN
      retention on endothelial cells of lung and viscera. By direct continuous
      monitoring and quantitation of INN at the end of CPB, a sensitive technique for
      quantitation of neutrophil kinetics, margination, and retention during CPB was
      developed.

PMID- 8555576
TI  - Tumor necrosis factor monoclonal antibody prevents alterations in leukocyte
      populations during cardiopulmonary bypass.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been implicated as causing the
      systemic inflammatory response to cardiopulmonary bypass (CPB) that contributes
      to the postoperative sequelae of coagulopathy, increased capillary permeability,
      leukocytosis, fever, and multiple organ dysfunction. To define the role of TNF
      alpha on leukocyte populations during CPB, pigs (n = 6) were pretreated with 20
      mg TNF-alpha monoclonal murine antibody before normothermic CPB (2 hr) in a
      blinded prospective randomized study with saline used as a control (n = 6). The
      leukocyte response to CPB was measured at 10, 30, 60, and 120 min during CPB and
      at 60 and 120 min after CPB. Repeated measures analysis of variance was performed
      and the null hypothesis was discarded at the 5% level. The control group
      displayed the typical leukocyte profile associated with CPB: and initial
      leukopenia (36% reduction) followed by leukocytosis (11% increase, P = 0.0001).
      The initial leukopenia was due to a fall in both polymorphonuclear neutrophils
      (33% reduced, P < 0.05) and monocytes (37% reduced, P < 0.05). In the TNF-alpha
      monoclonal murine antibody group the total leukocyte profile did not change
      significantly from baseline, (8.7% reduction to a 16% increase, P = 0.24) nor
      were there significant changes in populations including neutrophils and
      lymphocytes. In the treatment group the initial reduction in monocytes was
      prevented and total circulating monocytes increased during bypass. The
      experimental data suggest that TNF-alpha may play an important role in the early
      alterations in leukocyte populations associated with CPB, and TNF-alpha
      monoclonal murine antibody pretreatment ameliorates the leukocyte response.

PMID- 8555577
TI  - Reversal of anticoagulation without protamine using a heparin removal device
      after cardiopulmonary bypass.
AB  - Protamine sulfate is routinely administered after cardiopulmonary bypass to
      reverse systemic heparinization, but may cause a severe hypotensive reaction in
      as many as 2% of patients. Research Medical, Inc., has developed an
      extracorporeal venovenous heparin removal device (HRD) for use in patients at
      high risk for a protamine reaction. Circulation through the HRD removes heparin
      by hollow fiber plasma separation and selective sorption of anionically charged
      heparin to a polycationically charged poly-L-lysine ligand coupled to a agarose
      substrate. The heparin depleted plasma then reenters the whole blood pathway and
      is returned to the patient through the double lumen catheter in the right atrium.
      To evaluate the HRD in a clinically relevant model, cardiopulmonary bypass was
      performed in pigs using RA-Ao cardiopulmonary bypass (120 min) with systemic
      heparinization (300 IU/kg), a nonpulsatile pump with a membrane oxygenator, and
      systemic hypothermia (28 degrees C). Group 1 (HEP n = 7) had no intervention to
      neutralize the heparin; Group 2 (HRD n = 7) used the HRD. After 19.7 +/- 4.2 min
      of circulation through the HRD, the activated clotting time had returned to
      baseline, whereas the pigs in the HEP group were still anticoagulated (activated
      clotting time = 396 +/- 152 sec; time to baseline was 124 +/- 9 min). There were
      no significant differences between groups with respect to hemodynamics,
      hematocrit levels, leukocyte profiles, or platelet counts, HRD is an effective
      heparin removal device in a pig model of cardiopulmonary bypass and awaits a
      phase I clinical trial in humans.

PMID- 8555578
TI  - Coagulation patterns during deheparinization with immobilized polycation.
AB  - Reversal of systemic heparinization with protamine is problematic during
      perfusion with heparin surface coated devices because protamine reacts with both
      circulating and surface bound heparin. Hence, the development of a
      deheparinization device allowing for ex vivo heparin absorption by the means of
      an immobilized polycation is of prime interest for a number of indications. To
      assess the coagulation patterns during ex vivo deheparinization, a heparin
      surface coated venovenous pump loop including a plasma separator with immobilized
      polycation was studied in a bovine model (n = 6, body weight 71 +/- 5 kg). After
      systemic heparinization with 300 IU of heparin/kg body weight, spontaneous
      evolution (control) of coagulation parameters was compared to ex vivo
      deheparinization with a mean pump flow of 500 ml/min. No device failure occurred
      during the procedures and all plasma separators remained patent. These baseline
      levels were measured for control versus ex vivo deheparinization: activated
      coagulation time 158 +/- 6 sec (161 +/- 4 sec: NS), antithrombin III 101 +/- 5%
      (108 +/- 8%: NS), fibrinopeptide A 3.4 +/- 1.7 ng/ml (4 +/- 1.7 ng/ml: NS). After
      heparin application mean activated coagulation time was longer than 1000 sec in
      both groups. Sixty minutes later, the activated coagulation time was 757 +/- 43
      sec (184 +/- 5 sec: P < 0.05), antithrombin III was 96 +/- 12% (99 +/- 2%: NS),
      and fibrinopeptide A was 2.7 +/- 0.7 ng/ml (9.5 +/- 3.5 ng/ml: P < 0.05). It is
      concluded that ex vivo deheparinization resulted in significant acceleration of
      activated coagulation time normalization. Fibrinopeptide A production in the
      group with ex vivo deheparinization appeared to be higher. As antithrombin III
      levels were close to normal in both groups, allowing for adequate function of
      circulating as well as surface bound heparin, and the coagulation process was
      blocked by significant heparin levels in the control group, the difference for
      FPA may be due to activation of the coagulation process in the surgical field
      (sternotomy).

PMID- 8555579
TI  - An assay to measure antibiotic efficacy against Staphylococcus epidermidis
      biofilms on implant surfaces.
AB  - Infection is a major limitation of implantable devices. Optimal antibiotic
      therapeutic regimes have not yet been defined. Implant-associated infections have
      a number of differentiating characteristics, which include the predominance of
      Staphylococcus epidermidis and other skin bacteria of normally low pathogenicity
      as the causative agents, together with a relative resistance to host defenses and
      to antibiotic therapy. These properties have been ascribed to the ability of the
      bacteria to exist on implant surfaces in the biofilm phase, which is protective.
      An assay of antibiotic activity using a standardized bacterial biofilm
      preparation of S. epidermidis is described. The assay is used to evaluate the
      relative efficacy of antibiotics to sterilize the biofilm, when they are used
      singly, or in double or triple combinations. The modulating effects of changing
      antibiotic concentrations and modifying the environment with CAPD variables
      (fresh and spent dialysis fluid, common PD solution additives) are also measured
      and the data summarized. It is hoped that, by using this and similar assays,
      individualized optimal therapeutic regimes of implant-associated infections may
      be logically planned.

PMID- 8555580
TI  - Effect of perfluorochemical emulsion on blood trauma and hemorheology.
AB  - One of the major problems of development and improvement of heart assist devices
      is the reduction of blood cell damage. The extremely high levels of shear stress,
      turbulence, prolonged contact between blood and foreign surfaces, and other
      abnormal hydrodynamic circumstances have been shown to cause hemolysis,
      activation of platelets, and changes in mechanical properties of red blood cells.
      Hemolysis, in turn, can drastically increase red blood cell aggregation at low
      shear conditions. A new pharmacologic approach to reduce blood trauma and improve
      rheologic properties of blood subjected to mechanical stress was investigated.
      These experiments showed that the replacement of 20% of the plasma volume with
      Fluosol (Alpha Therapeutic Corp., Los Angeles, CA), a perfluorochemical that
      transports oxygen, reduced mechanical fragility of human (P < 0.01) and ovine (P
      = 0.054) red blood cells by approximately 30%. The same replacement of plasma
      with Fluosol reduced hemolysis (plasma free Hb) by approximately 40% compared to
      control (P < 0.05) during in vitro pumping of blood with a centrifugal pump. A
      20% replacement of plasma volume with Fluosol remarkably reduced low shear blood
      viscosity (from 31.9 +/- 6.1 to 18.2 +/- 4.8 cP, for shear rate gamma = 0.277 sec
      1) and erythrocyte sedimentation rate (from 16.7 +/- 9.2 to 3.1 +/- 3.1) mm/hr)
      in human blood. Decrease of these parameters indicates the reduction of red blood
      cell aggregation. Results of this study demonstrate the potential feasibility of
      Fluosol to improve mechanical properties of blood in patients with heart assist
      devices.

PMID- 8555581
TI  - A peritoneovenous shunt with an access port enables non surgical reversal of
      intraperitoneal catheter occlusion.
AB  - Management of chronic peritoneal ascites by transfer of the fluid to the right
      atrium via peritoneovenous shunt (PVS) is often complicated by occlusion of the
      peritoneal catheter by one, or a combination, of the following: 1) omental
      plugging of drain holes, 2) fibrin obstruction of the lumen, and 3) encapsulation
      of the peritoneal segment by a cocoon. A PVS design that includes an access port
      facilitates the reversal of fibrin obstruction by urokinase. Eight dogs with
      implanted PVS were tested weekly for patency (indicated by the flow rate of
      saline into the peritoneum via the access port) and performance (indicated by the
      percent transfer of saline from the peritoneum to the vasculature). In 256 test
      sessions performed to date, 15 catheter occlusions occurred. Nine of these were
      reversed by one or two flushes with 5,000 units of urokinase via the access port.
      The remaining six were found to be occluded by cocoons (two), omentum (three),
      and fibrin (one). Although it is an effective treatment for ascites, the PVS is
      not in common use, because it has a relatively high occlusion rate. The access
      port and other features of the authors' PVS are designed to reduce the incidence
      of PVS occlusion.

PMID- 8555583
TI  - Microporous polymer surfaces prepared by an excimer laser ablation technique.
AB  - This paper presents an excimer laser microprocessing method to prepare
      microporous polymer surfaces. The irradiation of a KrF excimer laser (248 nm) was
      applied to several polymer films by passing a laser pulse through an optical
      microscope, resulting in ablative photodecomposition. The control unit was
      designed to control the fluence of the laser, pulse number, size of irradiated
      areas, and irradiation micropositioning. The ablation depth linearly increased
      with an increase in the accumulation of pulses. The chemical composition of the
      ablated surfaces did not vary with the accumulation of pulses, confirmed by x-ray
      photoelectron spectroscopy measurements. Excellent structuring quality of ablated
      micropores was obtained for polyurethane, polyimide, and polycarbonate films. As
      an application of the ablation technique, polyurethane films were micropored by
      the excimer laser ablation technique in conjunction with open-cell structured,
      small diameter grafts under development. In vitro cell ingrowth and compliance on
      the micropored polyurethane films were examined. Rapid ingrowth was observed on
      pore sizes of a few microns to several tenths of a micron in diameter. Higher
      density micropores provided enhanced elastomeric properties.

PMID- 8555582
TI  - Fabrication of resorbable microporous intravascular stents for gene therapy
      applications.
AB  - The authors have produced resorbable, microporous endoluminal stents from Poly-L
      lactic acid (PLLA)/Poly epsilon-caprolactone (PCL) blends. Both helical and tube
      stent designs have been obtained by solvent casting and flotation-precipitation
      fabrication techniques. A range of PLLA/PCL blend ratios and process variables
      were employed to investigate their influence on mechanical properties, porosity,
      and degradation rate. Polymer blends with higher PLLA proportions exhibit higher
      elastic moduli and ultimate tensile strength, and lower elongation, porosity, and
      degradation rates than do materials with higher PCL content. Stents with suitable
      mechanical properties for deployment and support of the vessel wall were
      obtained. Poly(ethylene oxide) was incorporated into these devices using an acid
      swelling technique, opening the pore structure and improving the hydrophilic
      character, thereby enabling the uptake of recombinant adenoviral vectors. The
      50:50 PLLA/PCL blended stents were impregnated with recombinant adenovirus (AdCMB
      beta Gal, encoding a nuclear localizing variant of Escherichia coli beta
      galactosidase). Cultured CV-1 cells incubated with stents impregnated with the
      recombinant virus expressed nuclear localized beta-galactosidase activity,
      confirming that absorbed virus is released from the matrix in an infectious form,
      with kinetics suggesting that genetically enhanced endovascular devices of this
      design are feasible.

PMID- 8555584
TI  - Microfabricated surface designs for cell culture and diagnosis.
AB  - Grooved and holed surfaces with a well fabricated design may serve as
      microsubstrates for cell culture and microreactors for diagnosis. In this study,
      the authors prepared chemically treated, micrometer scale grooved and holed glass
      surfaces by combined surface modification and ultraviolet (UV) excimer laser
      ablation techniques, as follows. 1) Microcell-culture substrate: Amino group
      attached glass surfaces, prepared by the treatment with an aminopropylsilane,
      were condensed with a carboxylated radical initiator. Subsequently,
      polyacrylamide was grafted by surface initiated radical polymerization to create
      a very hydrophilic surface layer. Ultraviolet excimer laser beams (KrF: 248 nm)
      were irradiated through a microscope onto surfaces to create grooves or holes
      that were 10 and 50 microns in width or diameter, respectively. The depth,
      depending on the irradiation light strength, ranged from a few to several tenths
      of a micrometer. On endothelial cell (EC) seeding, ECs adhered and grew on the
      bottoms of the grooved or holed surface where glass was exposed on ablation.
      Little cell adhesion was observed on non ablated, grafted surfaces. Endothelial
      cells aligned along the groove, resulting in very narrow tube like tissue
      formation, whereas ECs tended to form a multilayered spherical aggregate in a
      hole. A single cell resided in a 10 microns square hole. 2) Microreactor for
      diagnosis: The glass surface, treated with a fluorinated silane, was ablated to
      create round holes. On addition of a few microliters of water, water could be
      quantitatively transferred into a hole because of the water repellent
      characteristics of non ablated, fluorinated glass. As a model of a microreactor,
      enzyme reactions to affect different levels of glucose were carried out in tiny
      holed surfaces.

PMID- 8555585
TI  - Activation of plasma components by leukocyte removal filters.
AB  - The technique of leukocyte filtration has been introduced into cardiac surgery to
      reduce leukocyte mediated reperfusion injury. When autologous whole blood (WB) is
      used as filtrate, it is more likely to be activated by the filter material than
      are banked red blood cell concentrates (RCC), because of its richness in plasma
      components. This study was designed to compare the activation of plasma
      components during leukocyte filtration from WB (n = 10) taken from the heart-lung
      machine, with RCC (n = 10) obtained from the blood bank. Leukocyte filters made
      from either cellulose acetate or polyester were used. Blood samples were taken
      simultaneously from the inlet and outlet of the filter after filtration of either
      700 ml of WB or 350 ml of RCC. Results indicated that the complement cascade was
      activated, as reflected by the increase of C3a and C5a during filtration of WB by
      filters made from cellulose acetate. In contrast, there was no significant
      increase of C3a and C5a during filtration of RCC. The clotting system, indicated
      by fibrinopeptide A, and the fibrinolytic system, indicated by fibrinogen
      degradation products, were not activated during leukocyte filtration. These data
      suggest that it is the WB taken from the heart-lung machine rather than the RCC
      from the blood bank that is being activated during leukocyte filtration. Thus,
      careful selection of filter material is important for leukocyte filtration of
      autologous whole blood during cardiac surgery.

PMID- 8555586
TI  - Markers of thromboembolization in a bovine ex vivo left ventricular assist device
      model.
AB  - The production of blood microemboli (BME) was studied using an ex vivo
      exteriorized left ventricular assist device (LVAD) model in calves. Each of eight
      calves received a series of three LVADs, each operating for 24 hr. Blood
      microemboli were measured directly by a laser (624 nm and 828 nm) light
      scattering microemboli detection (LSMD) system through the LVAD outflow cannula
      and by constant pressure filtration (CPF) of blood samples from the LVAD outflow
      cannula. Hematologic parameters were also measured. After LVAD removal,
      perivalvular thrombi were evaluated using polar coordinate mapping. The average
      LSMD and CPF results correlated. For example, in one series of three calves, one
      ventricle exhibited significantly greater thrombogenesis than did the other
      ventricles, as indicated by both the LSMD and CPF results. In a series of five
      calves, one calf developed an abnormally high activated thromboplastin time
      (APTT), even in the absence of heparin. For two of the three ventricles tested in
      that calf, microemboli concentration (CPF), Factor XII activity, level of fibrin
      degradation products (FDP), and accumulated thrombus were significantly lower
      than for the other calves. The whole blood viscosity (WBV, at 230 s-1) in this
      calf also decreased to lower values than were seen with the other calves.

PMID- 8555587
TI  - Leukocyte adhesion molecules as biocompatibility markers for hemodialysis
      membranes.
AB  - Comparative flow cytometric measurement was used to evaluate the significance of
      leukocyte adhesion molecule (LAM) activity changes during hemodialysis (HD) with
      different cellulosic and non cellulosic membranes. Six hemodialysis patients
      (men) who were in a maintenance program for more than 6 months were treated
      consecutively with five different dialyzers (cuprophan, hemophan, 2 types of
      cellulose acetate, and polysulfone). During each study HD, blood was sampled from
      the arterial line at 0, 15, and 60 min and from the venous port at 3 min to
      harvest leukocytes immediately after the first cell-membrane contact. After whole
      blood lysis preparation, leukocytes were incubated with fluorescent antibodies to
      label LAM CD 11A/18 (LFA-1), CD 11B/18 (Mac-1), CD 11C/18 (p150/95), and CD 54
      (ICAM-1) (Becton-Dickinson, San Jose, CA). Data were acquired for the
      granulocyte, monocyte, and lymphocyte population based on forward and 90 degrees
      scatter light measurements. Accuracy of gating was verified by CD 14/45 staining
      for all samples. Baseline integrin expression for the selected populations before
      biomaterial contact was found to be heterogeneous for different patients, but
      underwent changes for the same patient during HD treatment. The fluorescent
      intensity corresponding to specific integrins was characterized by different
      patterns of up/down regulation with maximal deviations occurring at 3 min.
      Fluorescent intensity of the granulocyte and monocyte populations sampled at 15
      min was 40-50% lower as compared with those sampled immediately after the first
      biomaterial contact. Based on the basal fluorescence levels and values recorded
      after the first biomaterial contact and those at 15 min, two coefficients were
      generated to compare membrane properties.

PMID- 8555588
TI  - Measurement of CD11/CD18 integrin expression on the polymorphonuclear cell
      surface after incubation with synthetic vascular prostheses.
AB  - Polymorphonuclear (PMN) cell activation in the presence of synthetic vascular
      grafts was studied by using flow cytometry to measure CD11/CD18 leukocyte
      adhesion molecule expression at the cell surface. Polymorphonuclear cells
      isolated from the blood of 10 healthy human donors were incubated with six
      knitted polyester vascular prostheses (Vasculour II, Albumin-Coated Graft,
      Triaxial, Gelatin-Impregnated Gelseal, Dialine I, and Bovine Collagen-Impregnated
      Dialine II) for 60 min at 37 degrees C. The authors' study demonstrated that
      CD11/CD18 integrin expression varies among donors for a given vascular
      prosthesis, and that each donor has his or her own pattern of responsiveness
      toward synthetic vascular grafts. The current study indicates that PMN activation
      measured by CD11/CD18 integrin expression is a sensitive method of measuring the
      blood compatibility of a given foreign surface for a given patient.

PMID- 8555589
TI  - Surface modifying additives for improved device-blood compatibility.
AB  - Copolymers composed of polar and nonpolar blocks, when blended with a base
      polymer in low concentrations, migrate to the base polymer surface during and
      after fabrication. Migration of these surface modifying additives (SMAs)
      dramatically changes the outermost surface molecular layers that comprise the
      region that determines biocompatibility. The blood compatibility of
      cardiopulmonary bypass and hemodialysis components have been improved by using
      SMA blended polymers or SMA coated surfaces. The particular SMAs used were a
      series of triblock copolymers with a general formulation of polycaprolactone
      polydimethylsiloxane-polycaprolactone. X-ray fluorescence (XRF), fourier
      transform infrared (FTIR), refractive increments (RI), and gel permeation
      chromatography (GPC) were used to characterize the molecular weight of SMA and
      the bulk concentration of SMA after blending. Electron spectroscopy for chemical
      analysis (ESCA) proved that the surface of blended polymers was highly saturated
      with SMA. Results of in vitro experiments with human blood demonstrated that SMA
      blended polymers delay contact activation (kallikrein-like activity), reduce
      coagulation activity (thrombin-antithrombin [TAT] generation), and do not
      adversely affect complement activation (terminal complement complex [TCC]
      generation) or mononuclear cells activation (IL-1 beta production). Ex vivo
      canine AV shunt studies showed improvement of platelet compatibility of SMA
      blended polymers. Reduction of cellular and protein system activation by using
      components fabricated with SMA blood contacting surfaces can potentially result
      in reduced morbidity associated with extracorporeal circulation.

PMID- 8555590
TI  - Magnetic resonance study of virgin and explanted silicone breast prostheses. Can
      proton relaxation times be used to monitor their biostability?
AB  - The development of sensitive and non invasive magnetic resonance (MR) techniques
      for monitoring the fate of silicones in breast prostheses in vivo requires
      detailed knowledge of the MR properties of these silicones. To characterize
      changes in the proton dynamics, relaxation time measurements (T1 and T2) were
      obtained on virgin and explanted breast prostheses using both spectroscopic and
      imaging techniques in a magnetic field of 1.5 Tesla. Averaged transverse
      relaxation times (T2) were observed to depend neither on the measurement
      technique employed (virgin silicone, T2 = 160 +/- 5 msec with imaging and 154 +/-
      9 msec spectroscopically) nor on the effect of being implanted in the body for
      various periods of time ranging from 4 months to 17 years (explanted silicone, T2
      = 164 +/- 16 msec with imaging and 159 +/- 25 msec spectroscopically). Average
      longitudinal relaxation times (T1) were also found to be similar for virgin and
      explanted prostheses (virgin silicone T1 = 899 +/- 32 msec, explanted silicone T1
      = 879 +/- 75 msec, measured with imaging), but appeared to depend on the
      measurement technique employed (virgin silicone T1 = 764 +/- 17 msec, explanted
      silicone T1 = 765 +/- 23 msec, measured spectroscopically). Although the measured
      relaxation times did not reveal any differences between virgin and explanted
      prostheses, marginal differences were detected between the relaxation times of
      explanted prostheses from different manufacturers. More reference data on
      standard silicone products may be required before changes in implanted silicone
      can be assessed using proton magnetic relaxation times.

PMID- 8555591
TI  - Collagen fiber architecture of bovine pericardium.
AB  - Small-angle light scattering (SALS) was used to quantify the collagen fiber
      architecture of 12 bovine pericardium (BP) specimens overlying the right and left
      anterior surfaces of the heart. The collagen fiber architecture was described in
      terms of preferred collagen fiber directions, volume fractions (Vf), and degree
      of orientation. To explore the relationship between BP collagen architecture and
      mechanical anisotropy, biaxial mechanical tests were performed on two specimens
      chosen for their extremes of collagen fiber architecture. About 38% of the SALS
      test locations showed the occurrence of two distinct collagen fiber populations,
      with the primary population Vf typically 90%. Structurally, the left anterior
      specimens appeared to be the most homogeneous, with an overall preferred
      direction close to the circumferential direction of the heart. The right side
      specimens were inconsistent, with a broad range of fiber orientations. The
      direction of greatest stiffness was consistent with the underlying collagen fiber
      architecture. Overall, these results suggest that 1) the mechanical behavior of
      BP is quantitatively consistent with its collagen fiber architecture; 2) the
      variability of BP mechanical anisotropy is caused by variations in collagen fiber
      preferred directions; and 3) the left anterior side of the bovine pericardial sac
      might be a good material selection site for bioprosthesis fabrication.

PMID- 8555592
TI  - Plasmapheresis versus plasma perfusion in acute Guillain-Barre syndrome.
AB  - Guillain-Barre Syndrome (GBS) is an acute post infectious or disimmune illness
      that affects nerve roots and peripheral nerves. Multicenter studies have clearly
      shown that plasma exchange (PE) provides valuable amelioration of GBS. It was
      recently suggested that plasma perfusion (PP) on phenylalanine columns displays
      the same therapeutic effects of PE in neuroimmunologic disorders, without the
      infectious risks linked with plasma replacement. In this study, the authors
      compared the efficacy of PE versus that of PP in two groups of patients suffering
      from GBS by investigating the clinical outcomes and the electrophysiologic and
      cerebrospinal fluid findings. Of 22 patients suffering from GBS, 16 underwent
      seven sessions of PE in a mean time of 15 days (Group A). Six patients, showing
      the same clinical pattern, underwent three sessions of PP in a mean time of 10
      days (Group B). Data reported in Group A show that PE: 1) stops the progressive
      worsening of the disease, 2) prevents the development of acute respiratory
      failure, 3) allows an early and significant clinical improvement with change in
      disability grade, and 4) improves motor conduction velocities and motor action
      potentials when recorded 45 days after the end of treatment. Data in Group B show
      that PP allows a slower and later improvement in disability grade, and
      electrophysiologic data recorded at the end of treatment was worse after 45 days.
      Finally, it may be concluded that PE has beneficial effects on GBS in terms of
      time of recovery, complication rate, and relapses. Plasma perfusion did not show
      the same results.

PMID- 8555593
TI  - Enhanced oxygen delivery induced by perfluorocarbon emulsions in capillary tube
      oxygenators.
AB  - Previous studies showed that a new generation of perfluorocarbon (PFC) emulsions
      increased tissue PO2 in the cat retina to a degree that could not be explained by
      the small increase in arterial O2 content seen after the infusion of low doses of
      1 g PFC/kg body weight. It seems that increased O2 delivery at the tissue level
      after PFC infusion is caused by a local effect in the microcirculation. The
      authors studies this effect in vitro at steady state in a closed loop circuit,
      consisting of one of two types of capillary tube oxygenators, deoxygenator(s), a
      reservoir bag filled with anticoagulated bovine blood or saline (control), and a
      roller pump, to see if the addition of PFC would have an effect on the PO2
      difference (delta PO2) across the capillary tube membrane oxygenator at a blood
      flow rate of 3 l/min. Perfluorocarbon was added in three incremental doses, each
      giving about 0.7 vol% of PFC. The delta PO2 across the oxygenator was measured
      before and after each dose. The mean percent increases in delta PO2 in blood for
      two types of oxygenators were 19.2 +/- 8% (mean +/- SD, n = 6, P = 0.002) and 9.9
      +/- 4% (n = 3, P = 0.05), respectively, whereas the mean percent change in delta
      PO2 in saline was -4.9 +/- 2% (n = 2, P = 0.2). Inlet PO2s to the oxygenator were
      only minimally increased. The authors conclude that O2 delivery was significantly
      enhanced after injection of PFC in blood in this capillary tube model. A near
      wall excess of PFC particles may account for the augmentation of O2 diffusion in
      this model.

PMID- 8555594
TI  - Perfluorocarbon oxygen transport. A comparative study of four oxygenator designs.
AB  - Improvements made in current generation perfluorocarbon emulsions (PFCEs) warrant
      renewed interest in PFCEs as an oxygen (O2) carrying substance during
      cardiopulmonary bypass (CPB). Before embarking on in vivo studies of PFCEs during
      CPB, an in vitro study was designed to: 1) demonstrate increased O2 content
      attributable to PFCEs, and 2) compare O2 transfer to a PFCE crystalloid mixture
      by four oxygenator designs (one bubble oxygenator, two hollow fiber membrane
      oxygenators, and one silastic membrane oxygenator). A circuit was designed to
      circulate fluid between a deoxygenating device and a test oxygenator. In protocol
      I, either a crystalloid solution or a crystalloid PFCE mixture was circulated
      through bubble oxygenators at flows ranging from 0.5 to 3 l/min, and at
      temperatures of 4, 20, 30, or 40 degrees C. In protocol II, a crystalloid PFCE
      mixture was circulated at flows ranging from 0.5 to 6 l/min at temperatures of 4,
      20, 30, or 40 degrees C. Four different oxygenator designs were compared using
      the in vitro test circuit. The comparison variables for protocols I and II were
      arterovenous oxygen (AVO2) difference and O2 transfer rate measured at each flow
      for each temperature. Protocol I showed that the AVO2 differences and O2 transfer
      rates were higher in the crystalloid PFCE mixture than in the crystalloid
      solution, although statistical comparison was precluded by the small sample size.
      In protocol II, the hollow fiber and silastic membrane oxygenators had higher (P
      < 0.05) AVO2 differences and oxygen transfer rates than the bubble oxygenators at
      all flows and temperatures tested. Future trials to evaluate PFCEs during
      cardiopulmonary bypass should use hollow fiber or silastic membrane oxygenators,
      rather than bubble oxygenators, to maximize transfer of O2 to the PFCE.

PMID- 8555595
TI  - Extracorporeal endotoxin removal in a canine model of septic shock.
AB  - The authors induced endotoxic shock in an animal model and attempted to treat
      this state by direct hemoperfusion over a modified anion sorbent column. It has
      been shown that the reversal of septic shock correlates with the efficiency of
      extracorporeal endotoxin removal. In this experiment, there were five control
      animals (sham) and five test animals (hemoperfusion over sorbent column). The
      efficacy of treatment was evaluated by survival at 24 hr, changes in mean
      arterial pressure, blood-acid base balance, and plasma endotoxin levels. There
      was 0% survival in the control group and 100% survival in the test group. The
      control dogs never recovered from shock or metabolic acidosis, but the test
      animals were at their initial values for these parameters by 6 hr. The endotoxin
      levels measured at 6 hr were higher in the control group (265 +/- 88 ng/ml) as
      compared with the test group (7.0 +/- 6.2 ng/ml). Direct hemoperfusion over a
      modified sorbent column effectively removed endotoxin and reversed the course of
      fatal septic shock.

PMID- 8555596
TI  - Clinical trials of a cryoglobulin filter.
AB  - The authors report the results of clinical trials of a high capacity cryoglobulin
      filter (Cryofilter) in seven patients with cryoglobulinemia unresponsive to high
      doses of prednisone or immunosuppressive drugs who required plasmapheresis. The
      objective of this study was to test the safety and efficacy of the cryofilter in
      a limited patient population according to the investigational Device Exemption
      guidelines of the FDA. The cryoglobulins were selectively filtered from plasma at
      4 degrees C by a cryofilter characterized by a membrane surface area of 0.135 m2
      and an average pore size of 4.3 microns. Safety was evaluated by patients vital
      signs, complement activation, and clinical score of symptoms in the course of 10
      treatments. Efficacy of cryofiltration was evaluated by comparing sieving of the
      cryoglobulins to that of albumin; immunoglobulins G, A, and M; and fibrinogen.
      All seven patients completed the series of 10 treatments without notable
      complement activation or any signs of discomfort. The cryofilter was particularly
      selective in patients with high cryoglobulin concentrations. Improvement in
      clinical symptoms was observed in all patients.

PMID- 8555597
TI  - Oxidative damage to RBC membranes and pentose phosphate shunt activity in
      hemodialysis patients after suspension of erythropoietin treatment.
AB  - During follow-up of anemic hemodialysis patients (HDP) treated with recombinant
      human erythropoietin (rHuEpo), it was noticed that in five HDP, some time after
      suspension of rHuEpo, hemoglobin (Hb) levels remained at acceptable levels. A
      metabolic block of the pentose phosphate shunt (PPS) has been described in HDP,
      which leads to increased oxidative damage of red blood cell (RBC) membranes and
      increased susceptibility to hemolysis. The increased production of short-chain
      fatty aldehydes, including malonyldialdehyde (MDA), is an appropriate index of
      oxidative damage. This study aimed to verify whether the maintenance of
      acceptable levels of Hb was related to a change in RBC membrane oxidative damage
      and pentose phosphate shunt activity. In the five HDP in question who required
      rHuEpo (150 U/kg/week) for severe anemia (Hb = 7.48 +/- 0.95 g/dl), after a
      stable level of Hb > 10 g/dl was reached for at least 1 month, rHuEpo treatment
      was stopped. Hb levels remained adequate (Hb = 10.68 +/- 0.77 g/dl) after 14.6 +/
      7.64 months. The oxidative damage was evaluated by measuring RBC MDA
      (microgram/ml packed RBC) basal levels, and PPS activity by measuring MDA levels
      after incubation with ascorbate and cyanide (delta % RBC MDA production). Ten
      anemic HDP not treated with rHuEpo were used as controls (Hb = 8.12 +/- 1.32
      g/dl). It was found that the maintenance of adequate levels of serum Hb after
      suspension of rHuEpo therapy is related to a decrease in RBC membrane oxidative
      damage (RBC MDA HDP = 2.40 +/- 0.41 vs. RBC MDA controls = 18.23 +/- 6.56; P <
      0.005) in consequence of the normalization of pentose phosphate shunt activity.

PMID- 8555598
TI  - Formal analytical solution to a regional blood flow and diffusion based urea
      kinetic model.
AB  - At the beginning of hemodialysis (HD), urea in arterial blood drops rapidly,
      whereas a pronounced postdialytic urea rebound (PDUR) can be observed when HD is
      discontinued. In a new approach to this observation, the authors suggest that
      solute flux from remote body compartments to the dialyzer is governed by 1)
      diffusion of solutes from the tissue to the blood perfusing the tissue, and 2) by
      regional blood flow distribution, cardiopulmonary recirculation, and access
      recirculation, respectively. These concepts were incorporated into a variable
      volume, two compartment model that could be treated as an eigenvalue problem and
      solved analytically. The resulting equations were used to model intradialytic and
      postdialytic urea profiles with the help of a commercial spreadsheet program. The
      significance of hemodynamic model parameters such as cardiac output (CO) and
      regional blood flow distribution on PDUR was modeled in simulation runs, where
      PDUR increased from 5% to 15% when CO fell from 7 to 3 l/min with standard
      treatment parameters (t = 3h, KD = 0.3 l/min, V = 35l, UFV = 2.8l, fQHFS = 0.8,
      QAc = 0.8l/min). Thus, this urea kinetic model establishes a previously missing
      link between hemodynamics and solute removal.

PMID- 8555599
TI  - Catheter related bacterial infections mimic reactions to exogenous pyrogens
      during hemodialysis.
AB  - Pyrogenic reactions are characterized by fever, chills, hypotension, or a
      combination of these developing during or shortly after hemodialysis in a
      previously asymptomatic patient. The temporal association with treatment
      implicates exposure of the patient's blood to bacterial pyrogens from
      contaminated dialysate or a reused dialyzer. Routine body temperature monitoring
      is recommended to detect these exposures. The current study was prompted by the
      appearance of several symptomatic febrile episodes in patients who were
      asymptomatic and afebrile before treatment with high-flux hemodialysis. During a
      6 month period, temperatures were measured with a digital oral thermometer before
      and after 9,605 high-flux hemodialyses in 163 patients. Elevations above 100
      degrees F (37.8 degrees C) were observed during or after 33 dialyses in 15
      patients. In 18 of these dialyses, the temperature was also elevated before
      treatment began. Four patients who had no symptoms or fever before dialysis
      accounted for febrile reactions during 11 of the remaining 15 dialysis
      treatments. Fever was accompanied by rigors during most of the episodes.
      Subsequent blood cultures grew Enterococcus faecalis (two), Enterobacter cloacae
      (two), and Pseudomonas aeruginosa and cepacia (one). All four patients had
      indwelling silastic double lumen venous catheters (PermCaths), all responded to
      intravenous antibiotics, and all required eventual removal of the catheter. The
      apparent precipitation of sepsis by dialysis indicates that shear forces caused
      by high pulsatile blood flow through the catheter may dislodge organisms that
      have colonized the lumen. Intraluminal instillation of antibiotics is suggested
      as a preventative measure.

PMID- 8555600
TI  - Dialysis fluid temperature and vasoactive substances during routine hemodialysis.
AB  - Blood pressure stability is better during cold hemodialysis (HD). This has mainly
      been attributed to a more pronounced sympathetic activation during cold than
      during warm HD. The authors studied the effect of dialysate temperature on
      vasoactive peptides, noradrenaline (NA), and renin (PRA). Ten hemodynamically
      stable patients were dialyzed for 240 min with each of two dialysate
      temperatures: 38.5 degrees C (warm HD = WHD) and 34.5 degrees C (cold HD = CHD).
      A decrease (P < 0.05) in blood pressure occurred during WHD; however, during CHD,
      blood pressure was stable. There were no differences in vasoconstrictors between
      the two regimens. There was a decrease in NA (P < 0.05), a tendency of PRA to
      increase (NS owing to a large statistical spread), while arginine vasopressin was
      unchanged. During CHD, there was a small increase in neuropeptide Y (NPY);
      however, during WHD, NPY only tended to increase. However, the relative NPY
      levels (percent of baseline levels) after WHD and CHD did not differ. The
      vasodilator response was similar during both treatments. Calcitonin gene related
      peptide was unaltered. Motilin tended to decrease initially, but then increased
      (P < 0.05) to baseline levels. An increase occurred in beta-endorphin (P < 0.05)
      and substance P(P < 0.01). There was an initial rise (P < 0.05) in vasoactive
      intestinal peptide (VIP), followed by a tendency to decrease during the remainder
      of treatment. The authors concluded that blood pressure stability was better
      during CHD. However, this was not reflected by differences in plasma levels of
      the vasoactive peptides, nor did they find any difference in the sympathetic
      drive between the two regimens.

PMID- 8555601
TI  - Low Ca2+ dialysate. Effects on bone metabolism in the course of paired filtration
      dialysis.
AB  - To evaluate the 1-year effects of PFD performed with low Ca2+ dialysate (1
      mmol/l) on calcium metabolism and on bone disease, the authors studied in eight
      patients who were previously treated with PFD performed with standard Ca2+
      dialysate (1.75 mmol/l). On samples from these subjects, the following were
      evaluated: 1) serum Ca2+ and PO4 levels, 2) serum PTH levels, 3) serum Al levels,
      and 4) bone morphology. All the patients were hypercalcemic, four with high serum
      PTH levels (high turnover bone disease, group 1) and four with low serum PTH
      levels (low turnover bone disease, group 2). In both groups, a decrease in serum
      Ca2+ and an increase in serum PTH was observed within the third month. In group
      2, PTH levels reached the normal range. Because serum Ca2+ levels decreased to
      normal in both groups, it was possible to administer oral CaCO3 (10.5 +/- 2
      g/day) to control serum PO4 and to stop Al gels. This did not induce any increase
      in serum Ca2+, whereas serum Al fell significantly. In group 1, to prevent a
      further rise in PTH, patients were treated with intravenous calcitriol (5 +/- 2
      micrograms/week). This induced a reduction in the serum PTH without increasing
      serum Ca2+ or PO4. Within 12 months, an improvement in bone morphology was seen
      in both groups. It is concluded that the use of low Ca2+ dialysate corrects
      hypercalcemia in patients with PFD treated with high oral doses of CaCO3, and
      improves low turnover bone disease. The combination of low Ca2+ dialysate and
      intravenous calcitriol also improves high turnover bone disease.

PMID- 8555602
TI  - Projection and simulation results of an adaptive fuzzy control module for blood
      pressure and blood volume during hemodialysis.
AB  - This paper proposes a fuzzy logic based procedure able to control the behavior of
      a patient's blood pressure during a dialysis session, allowing him to reach the
      planned dry weight. A proportional integrative discrete-time fuzzy control is
      used to subject the controlled variables (blood pressure and blood volume) to the
      reference values. Two different tables that refer to pressure and volume errors
      and rates are consulted and the proposed control actions are taken to obtain the
      final value (net ultrafiltration rate). A saturation-threshold function of
      volemia acts on the second control variable, Na concentration in the dialysate.
      The adaptive control system was simulated on an IBM PC, and rules and terms were
      expressed by linguistic judgments such as: IF "situation," THEN "action." A pre
      processor converts the rules into the numerical values in the tables. The
      obtained simulation results are satisfactory, and the introduction of Na control
      allows achievement of the target dry weight of the patient with a stable blood
      pressure.

PMID- 8555603
TI  - Hematocrit as an indicator of blood volume and a predictor of intradialytic
      morbid events.
AB  - Hematocrit (H) levels can change during hemodialysis, and these changes in H are
      inversely related to changes in blood volume (BV). The objectives of this study
      were to determine whether mean arterial pressure (MAP) decreases with decreasing
      BV and rising H during hemodialysis, and to determine the relationship between
      dialysis induced intravascular volume depletion and intradialytic morbid events
      (IME), defined as hypotension, cramping, or lightheadedness that led to dialysis
      staff intervention. We monitored H continuously using a noninvasive optical
      technique in 93 hemodialysis sessions in 16 patients. IME occurred in 48
      sessions. MAP decreased with increasing H in 10 of 16 patients (P < 0.05), but
      the relationship between MAP and H varied among the patients. The rate of BV
      change during sessions without morbidity (5.6 +/- 3.6 [SD] %/hr) was lower (P <
      0.001) than that preceding IME in the other sessions (12.2 +/- 5.5 [SD] %/hr).
      Twelve of 16 patients who exhibited recurrent IME during this study experienced
      these events when H reached a patient specific threshold. It is concluded that
      MAP decreases with decreasing BV and increasing H in many patients on
      hemodialysis, and that a high rate of BV change often indicates that IME are
      forthcoming. It is further hypothesized that a patient specific H threshold is
      indicative of a critical BV level below which certain patients experience IME.

PMID- 8555604
TI  - Deterioration of bioprosthetic heart valves.
AB  - The aim of this study was to detect biologic factors in the structural
      deterioration of bioprosthetic heart valves. Prostheses were removed from
      patients after 4-8 years of implantation and submitted to biochemical and
      morphologic assays. Successive staining of biologic sections revealed
      colocalization of lipids and glycosaminoglycans underneath calcifications in the
      disintegrated extracellular matrix. On biochemical assays, the amidolysis of
      synthetic peptide substrates indicated thrombin, plasmin, and tissue plasminogen
      activator activities in the nonhemocompatible leaflets; 0.15 mol NaCl, 0.05 mol
      Tris, and 5 mmol CaCl2 extracts from the prostheses cleaved the peptide substrate
      for collagenase and lysed gelatin gels. Polyacrylamide gel electrophoresis in
      sodium dodecyl sulfate disclosed the presence of low molecular mass polypeptides
      in extracts of the deteriorated prostheses. The detection of plasmin and
      collagenolytic enzyme(s), and the known broad proteolytic activity of plasmin,
      may point to the role of activation of the fibrinolytic system in the proteolytic
      degradation of bioprosthetic valves.

PMID- 8555605
TI  - The closing behavior of Medtronic Hall mechanical heart valves.
AB  - The rapid deceleration of mechanical heart valve leaflets or discs at closure,
      and their rebound after impact between the leaflets or discs and housing may
      produce conditions that favor cavitation inception. Precision measurements of the
      disc closing velocity using a laser sweeping technique (LST) were made on two
      Medtronic Hall (Med Hall) mitral valve models, the 29 mm Standard and D-16 Med
      Hall valves. The experiment was carried out in a pulsatile mock flow loop (PFL)
      by installing the tested valve in the mitral position of the PFL. Tests were
      conducted under physiologic pressures at heart rates of 70, 90, and 120 beats/min
      with flow rates of 5, 6, and 7.5 l/min, respectively. For each valve tested, the
      experimental series was carried out to include both a flexible mounting and a
      rigid mounting mechanism. The time history of the disc closing velocity during
      the last 3 degrees before final closure was measured. Results show that the disc
      approached the valve housing at a near constant velocity of approximately 1.3,
      1.5, and 2.0 m/sec for the Med Hall Standard valve, and 1.9, 2.5, and 2.6 m/sec
      for the Med Hall D-16 valve at 70, 90, and 120 beats/min, respectively. After
      impact, the valve of disc rebounded with velocities that depended on the mounting
      modalities and heart rates. In the rigid mounting, the disc rebound velocities of
      the Med Hall Standard and D-16 valves were about 60%-70% and 70%-80% of their
      respective approaching velocities. For the flexible mounting, the rebound
      velocities were 15%-25% and 20%-30% of their respective approaching velocities.
      The results demonstrate that a slight modification in the seat stop geometry of
      Med Hall valves can significantly affect disc closure behavior.

PMID- 8555606
TI  - In vivo evaluation of a trileaflet mechanical heart valve.
AB  - Design goals for a mechanical heart valve include duplicating the hemodynamic
      performance of the natural valve, eliminating the need for anticoagulants, and
      maintaining safety. The Lapeyre-Dassault (Dassault-Aviation, Paris, France)
      prosthetic valve, undergoing development, addresses these goals. The unique
      trileaflet design consists of a solid titanium ring and three leaflets.
      Prototypes of the valve fabricated with Delrin leaflets were implanted in the
      mitral position in six calves (70-90 kg). Four calves (Studies 1, 2, 3, 5) had
      long-term survival of 165, 158, 219, and 281 days, respectively. Two calves were
      killed, one on Day 37 and one on Day 39, after complications unrelated to the
      valve developed. In all calves heparin was given intravenously to maintain
      partial thromboplastin time at 1.5 to 2.0 x baseline for approximately 1 week. In
      Studies 1 and 2 full anticoagulation and antiplatelet therapy was given (orally
      administered sodium warfarin to maintain prothrombin time at 1.5 to 2.0 x
      baseline, along with aspirin (1 g/day) and dipyridamole 400 mg/day). In Study 3,
      all anticoagulation and antiplatelet therapy was discontinued at 1 month after
      implant. In Study 5, no anticoagulation therapy was given after the initial week
      of intravenous heparin; however, antiplatelet therapy was started on the fifth
      postoperative month and maintained until the study's end at 9 months. At 1, 2, 3,
      and 5 months, the mean plasma free hemoglobin level in the four long-term animals
      was 5.0 +/- 2.16, 6.0 +/- 3.83, 8.5 +/- 4.93, and 11.3 +/- 6.74 mg/dl,
      respectively. Hemolysis was not a problem. Valve performance during normal
      activity was excellent in all the calves, as evidenced by echocardiography and
      the overall appearance of good health. In the four completed long-term studies,
      left heart catheterization showed a mean valve pressure gradient of 11.57 +/-
      1.26 mmHg and no apparent valvular regurgitation. Histopathologic examination of
      major organs showed no evidence of thromboembolic events. This study shows that
      the innovative design of this trileaflet valve performed well in initial in vivo
      testing, justifying further development.

PMID- 8555607
TI  - A new antithrombogenic RV-PA valved conduit.
AB  - A new antithrombogenic right ventricular (RV)-pulmonary artery (PA) valved
      conduit was developed using a bovine jugular vein containing a natural valve. To
      maintain the natural and mechanical properties of the venous tissue, a
      hydrophilic cross-linking reagent, glycerol polyglycidyl ether polyepoxy compound
      (PC) was used instead of glutaraldehyde (GA). Moreover, to induce
      antithrombogenicity, heparin was bonded to the inner surface of the bovine
      jugular vein cross-linked with PC. Conduits of 18 to 20 mm inner diameter (ID)
      were implanted between the RV and PA in nine dogs weighing 7-17 kg, with the
      native main PA being ligated proximally. The handling and suturing of the graft
      was easy and adaptable, and the anastomosis was completed with excellent
      coaptation and no blood leakage at the suture lines. All animals were chronic
      survivors, but one animal died of hematemesis on the 438th postoperative day.
      Grafts were explanted from 182 to 385 days after implantation. The luminal
      surface of the conduits were white, glistening, and smooth with good coaptation
      of the cusps, without calcification or degenerative changes except for one cusp
      that showed a minimal deformation with a small thrombus. Macroscopic and
      microscopic observation showed that there were no thrombi at the anastomotic
      lines, but small thrombi on the luminal surface of the conduits near the cusps
      and in some cusps. Endothelium-like cells were noticed on the luminal surface of
      the graft, except in the area near the cusps, and on one cusp at 196 days after
      surgery. These results indicated that the new RV-PA valved conduit provided
      adequate antithrombogenicity by temporary slow heparin release, followed later by
      endothelialization of the graft in a low pressure system at 1 year after
      implantation.

PMID- 8555608
TI  - In vivo evaluation of an intraventricular electric axial flow pump for left
      ventricular assistance.
AB  - In vivo studies have begun to evaluate a new intraventricular electric axial flow
      left ventricular assist device (LVAD), the Jarvik 2000, which is a small,
      valveless pump that is placed inside the left ventricle through the left
      ventricular apex. The operation, which is performed through a left thoracotomy,
      may be done without cardiopulmonary bypass and aortic cross-clamping. Outflow is
      provided through a 16 mm softly woven, Dacron graft anastomosed to the descending
      thoracic or abdominal aorta. Pump flow, which varies from 2 to 16 l/min in vitro,
      is changed by adjusting the speed of pump rotation. Preliminary studies were done
      to evaluate the ease of implantation, hematologic and anatomic compatibility, and
      pump performance. The device has been implanted in seven healthy, preconditioned
      calves (83-138 kg), one of which is currently undergoing support. The
      implantation procedure averaged 3 hours. There were no operative deaths, and
      blood transfusions were not required. Postoperatively, anticoagulation was
      achieved with heparin followed by warfarin sodium to maintain prothrombin time or
      partial thromboplastin time at 1.5-2.0 times baseline. In the six completed
      studies, support time ranged from 2 to 120 days (mean, 36 days). The seventh calf
      has been supported for 30 days. In the four long-term studies (20, 70, 120, > 30
      days), the mean plasma free hemoglobin values during support were 11.0, 7.7, 6.6,
      and 3.4 mg/dl, respectively. Under normal conditions, the average daily flow rate
      ranged from 5 to 6 l/min. During treadmill exercise (10% grade, 1.5 km/h) lasting
      20 minutes, peak flow rates exceeded 8 l/min. These pilot studies suggest that
      this intraventricular axial flow pump is relatively easy to implant, operate, and
      control. In addition, it is hemocompatible, provides physiologic flow rates, and
      may be able to provide long-term circulatory support.

PMID- 8555609
TI  - In vitro and in vivo assessment of an intravenous axial flow pump for right heart
      assist.
AB  - Right ventricular (RV) function is a limiting factor in maintaining systemic
      circulation with circulatory assist. There is, however, no easy way to institute
      RV assist, such as the intraarterial axial flow pump (Hemopump) used for left
      heart assist. In this study, the feasibility and hemodynamic effect of
      intravenous use of an axial flow pump was examined. A pump system was developed
      with an outflow cannula and an impeller that were newly designed for intravenous
      insertion with a Hemopump driving system. The pump system characteristics using
      goat blood at a hematocrit of 26% indicated that maximum flow at a pressure
      differential against 40 mmHg is 3.2 l/min at a pump speed of 28,000 rpm. The pump
      was tested in adult goats by intravenous insertion through a 14 mm, low porosity
      graft anastomosed to the infrarenal inferior vena cava. The pump was advanced
      until the tip of the cannula was positioned at the main pulmonary artery, using
      balloon catheter guidance under fluoroscopy. RV assistance was evaluated by
      pressure tracing, and aortic flow (AF) measured by electromagnetic flowmeter
      under 1) induced pulmonary stenosis (PS), and 2) electrically induced ventricular
      fibrillation (VF) in combination with left heart assist. Under PS, right atrial
      pressure decreased from 11 to 2 mmHg and AF increased from 1.0 to 4.1 l/min after
      initiation of the pump. Under VF, AF and aortic pressure were 2.6 l/min and 78
      mmHg, respectively, with left ventricular assist. After initiation of the pump,
      they increased to 4.0 l/min and 98 mmHg, respectively. In chronic experiments
      using three adults goats for up to 48 hr, levels of plasma hemoglobin and
      platelet counts were maintained within an acceptable range. There was no
      prominent damage to the hearts. These data suggest that an axial flow pump
      introduced by an intravenous approach without thoracotomy is feasible and
      provides sufficient right heart assist.

PMID- 8555610
TI  - The development of an implantable artificial lung.
AB  - This report describes the development of an implantable gas exchange device. The
      device is composed of hollow fiber elements wound around a central open core
      enclosed in a compliant outer casing, offering very low resistance to blood while
      providing adequate gas exchange. The purpose of this study was to determine if
      this device design can completely support the gas exchange requirements of a
      large animal when the device is placed in series with the main pulmonary artery
      (PA). Six 40-80 kg adult sheep were used. The device was placed with vascular
      grafts anastomosed end to side on the proximal and distal main PA. The study
      began with the entire right ventricular blood flow being diverted through the
      device by occlusion of a snare around the PA between the vascular grafts. Total
      gas exchange then was provided by the device and the endotracheal tube was
      clamped. Results showed that this pumpless potentially implantable device is
      capable of completely supporting the gas exchange requirements of the
      experimental animals for up to 8 hours in the acute setting without significant
      change in cardiac index (CI) and oxygen consumption (VO2) compared with baseline.
      CI = 55.0 +/- 17.0 cc/min/kg versus 45.0 +/- 17.3 cc/min/kg. VO2 = 1.90 +/- 0.96
      cc O2/min/kg versus 2.08 +/- 0.54 cc O2/min/kg.

PMID- 8555611
TI  - Development of an intra blood circuit membrane oxygenator.
AB  - This paper deals with development of a prototype intra blood circuit membrane
      oxygenator. The shell of the oxygenator is made of a flexible polyvinyl chloride
      tube. The membrane surface area of the oxygenator is 0.3 m2. The total blood
      priming volume, including the oxygenator, was only 400-600 ml, which allows for
      extracorporeal circulation with no additional blood. Its potential was evaluated
      in in vitro experiments. The oxygen transfer rate was 140 ml/min, and the carbon
      dioxide transfer rate was 85 ml/min at a blood flow rate of 3 l/min. The device
      could make blood circuits simpler and more compact, with lower priming volumes.
      This indicates that it may prove useful for extracorporeal circulation.

PMID- 8555612
TI  - Effects of blood phase oscillation on gas transfer in a microporous intravascular
      lung.
AB  - It may be possible to design an intravascular membrane lung with gas transfer
      properties augmented by the natural flow oscillations in the venous and pulmonary
      circulation caused by the beating heart and ventilatory movements. The authors
      used a simple dye visualization technique, the Pierce-Donachy assist pump, and
      mass spectrometry to investigate these effects on membrane lungs made with
      tethered, blind-ended, microporous, polypropylene fibers using in vitro tests in
      water saturated with O2, CO2, and He. Prototypes were constructed on a 7.5 Fr
      pulmonary artery catheter. The fibers had an outer diameter (OD) of 380 microns
      and a wall thickness of 50 microns and were mounted on 4.8 mm OD sleeves. Control
      measurements were taken over a range of steady water flows from 0.4 l/min to 3
      l/min. While pumping the same water flow rates with a roller pump, the Pierce
      Donachy pump generated pulsatile flow at a rate of 45 beats/min and a systolic
      duration of 300 msec. This produced a phasic flow with an instantaneous average
      flow velocity varying from 0 to as high as 46 cm/sec. O2 and CO2 transfer
      increased by as much as 91% and 59%, respectively. The largest effects were seen
      at the lower water flow rates.

PMID- 8555613
TI  - Vibration analysis of vessel wall motion with intra vena caval balloon pumping.
AB  - The intravenous membrane oxygenator (IMO) incorporates a centrally positioned
      balloon surrounded by hollow microporous fibers. Previous studies using this
      configuration have demonstrated that rhythmic pulsation of the balloon enhances
      gas exchange, presumably by three dimensional convective mixing. This study
      sought to characterize vessel wall vibrations imparted by intra vena caval
      balloon pumping. An in vitro flow loop incorporating a current IMO prototype was
      used for these measurements. The IMO prototype was inserted in a modeled vena
      cava on which ultrasonic dimension transducers were mounted on the outer surface.
      The flow loop was operated at physiologic flow rates. The balloon was activated,
      and dynamic vessel diameter measurements were recorded as the pumping frequency
      was varied from 40 to 120 beats per minute (bpm). A Fast Fourier Transform
      algorithm generated a frequency spectrum at each bpm and for two different
      balloon configurations; a single balloon versus a tripartite arrangement, the
      authors' results demonstrate that the mean amplitude of vena caval oscillations
      varied with bpm, and that this variation followed the trends in oxygen transfer
      rates. This suggests that the motion of the vessel wall may contribute to
      convective mixing of blood. In addition, this work demonstrated significant
      differences in the frequency spectra associated with our two balloon
      configurations.

PMID- 8555614
TI  - Feasibility studies for a photosynthetic artificial lung. Optimization of
      parameters affecting photosynthesis.
AB  - As an alternative to conventional extracorporeal membrane oxygenation (ECMO)
      hardware, preliminary studies were conducted toward the development of a life
      support system based on biologic processes for the direct generation of O2 and
      removal of CO2 by the action of a photosynthetic organism. A high temperature
      strain of Chlorella pyrenoidosa, which functions optimally at 37 degrees C and pH
      7.4, was cultured in a 3 I fermenter with artificial lighting provided with Hg
      metal halide lights. The pH, total CO2 and partial pressure of oxygen (PO2) of
      the system were monitored at regular intervals using flow-through
      microelectrodes. The degree of importance of light intensity, substrate
      concentration, and cell density in the photosynthetic ability of Chlorella in
      batch culture were assessed over a 2 hour period. At high light intensities, the
      O2 production, CO2 removal, and pH changes were significantly greater than those
      at low irradiance levels. Over the range of HCO3- concentrations used in these
      experiments, the initial HCO3- levels did not appear to have a significant effect
      on the rates of O2 production/CO2 removal. The total amount of O2 produced/CO2
      removed and pH changes were found to be greater with higher cell densities. Under
      more optimal culture conditions, it may be feasible to eventually interface this
      photobioreactor with blood across a semipermeable membrane and catalytically
      convert blood CO2 to O2 directly, needing only an adequate light source.

PMID- 8555615
TI  - A dynamic intravascular artificial lung.
AB  - Intravascular lung assist devices (ILADs) must transfer sufficient amounts of
      oxygen and carbon dioxide to and from limited surface areas. It has become
      apparent that passive devices, i.e., those without an active means for enhancing
      transfer, cannot achieve sufficient transfer within the space available. High
      speed rotation or oscillation of fiber sheets can increase transfer rates up to
      800% over the rates achieved by a stationary device, judiciously configured fiber
      sheets cause an additional benefit when rotated: reduced resistance to blood flow
      across the device. The authors have developed a series of device prototypes based
      on these principles of transfer augmentation and minimization of flow resistance.
      The prototypes are small enough to fit inside the vena cava, with transfer
      surface areas ranging from 0.1 m2 to 0.5 m2. Transfer rates of O2 up to 53 ml/min
      and CO2 up to 51 ml/min and fluxes of 208 ml (min/m2) for O2 and 310 ml (min/m2)
      for CO2 have been achieved.

PMID- 8555616
TI  - A new cardiac wall substitute with high affinity for fibroblasts that can induce
      an endothelial cell lining.
AB  - A new cardiac wall substitute (PC graft) was developed using equine pericardium
      cross-linked with a polyepoxy compound. Compared with glutaraldehyde cross-linked
      pericardium (GA graft), the PC graft showed an approximately 10 times higher
      affinity for fibroblasts as measured by our in vitro cell migration and
      proliferation test. Six PC grafts (5 x 3 cm) were implanted into the right
      ventricular-pulmonary outflow tract position as a cardiac wall patch. Three GA
      grafts were used as controls. The PC grafts showed excellent handling during
      surgery because of their softness and elasticity. These grafts were explanted at
      2 and 7-8 weeks after implantation. All PC grafts showed a white and glistening
      surface without any thrombus formation except in one case where thrombus
      deposition was observed in the center of the graft. In the GA grafts, thrombus
      adhered to the luminal surface. Light microscopic observation showed that the PC
      graft surface was covered with a connective tissue layer and significant
      fibroblast infiltration. Approximately 60% of the area infiltrated by these
      fibroblasts was endothelialized, whereas in the GA graft, endothelialization was
      limited to within 2-5 mm of the suture line. Other areas were covered with a
      thrombus layer without any endothelial cells or fibroblast infiltration. PC cross
      linking can maintain the biologic and mechanical properties of the original
      materials. The PC graft offered excellent affinity for fibroblast migration and
      proliferation, which induced an endothelial cell lining on the surface. The
      results of this experiment indicated that the PC graft, which obtained the
      natural antithrombogenic property, was superior to a GA graft in terms of safety
      as well as mechanical, physiologic, and biologic properties as a cardiac wall
      substitute.

PMID- 8555617
TI  - A new apparatus for chronic observation of the microcirculation in situ to
      evaluate artificial organ performance.
AB  - Chronic study of the peripheral circulation and metabolism is very important in
      evaluation of artificial organ performance. However, there has been no way to
      observe the microcirculation in situ, chronically and continuously, without
      restriction. In this study, the authors developed a new apparatus that could be
      implanted and connected to an artificial organ that would allow continuous
      observation of the microcirculation while the subject is awake. The apparatus
      uses a charge coupled device (CCD) under a new principle: thin living tissue,
      such as mesentery, is put directly on a highly integrated CCD and
      transilluminated with a light emitting diode (LED). The vascular nets in the
      tissue are projected onto the CCD like a contact photograph, which is sent to a
      television screen and can be analyzed for motion and function. A 0.5 inch CCD
      with 25K pixels was used in this study. The cover glass of the CCD was removed so
      the tissue would be able to directly contact the CCD surface. The CCD, as well as
      LED, were molded with hard polyurethane as electrical insulation. The apparatus
      is 35 mm in diameter and 10 mm high with a micro stand for lighting with the LED,
      which is easy to implant in a goat or calf. The resolution of this apparatus was
      tested by putting a micro scale on the CCD surface. Several tenths of micrometers
      could be seen. In an animal experiment with a rabbit, configurations of
      arterioles and venules and their motions could be observed continuously for a
      night until the electrical insulation was broken. This method might be a strong
      weapon in artificial organs research.

PMID- 8555618
TI  - Performance evaluation of implantable artificial organs by sound spectrum
      analysis.
AB  - In this paper, a sound spectrum analyzing method was proposed to pre detect
      malfunctions of implantable artificial organs, such as an electromechanical total
      artificial heart (TAH) or prosthetic valves, without any percutaneous invasion.
      For this purpose, a sound detecting device was developed using a high sensitivity
      condenser microphone with a frequency range of more than 13 kHz. Output signals
      of this device are sampled at 100 kHz maximally, and sampled data are stored in
      an IBM PC (SamBo, Korea). To remove environmental noises in the measured sound,
      an adaptive least-mean square algorithm was employed. Using the squared value of
      the sound signal, the best position where only sounds from mechanical components
      can be measured was found. The sound spectrum was obtained by the periodogram
      spectral estimating method. Experiments were performed with this system, and the
      results indicated that: 1) by using an adaptive noise cancelling algorithm, a
      more noise-free signal can be obtained; 2) the harmonics from the mechanical
      components of a pendulum type electromechanical TAH were approximately 1.3 KHz;
      3) a spectral change was observed when we compared the power spectral densities
      of a normal and failed TAH; 4) the spectral shift to higher harmonics occurred
      with an increase in heart rate; and 5) the sound propagation properties of tissue
      were investigated with animal experiments. The method proposed was found to be
      applicable in the detection of implantable artificial organ mechanical failure by
      sound spectrum analysis without the need for percutaneous invasion.

PMID- 8555619
TI  - Modified fabrication techniques lead to improved centrifugal blood pump
      performance.
AB  - The authors are developing an implantable centrifugal blood pump for short- and
      medium-term (1-6 months) left ventricular assist. They hypothesized that the
      application of result dependent modifications to this pump would lead to overall
      improved performance in long-term implantation studies. Essential requirements
      for pump operation, such as durability and resistance to clot formation, have
      been achieved through specialized fabrication techniques. The antithrombogenic
      character of the pump has been improved through coating at the cannula-housing
      interfaces and the baffle seal, and through changing the impeller blade material
      from polysulfone to pyrolytic carbon. The electronic components of the pump have
      been sealed for implantable use through specialized processes of dipping and
      potting, and the surfaces of the internal pump components have been treated to
      increase durability. The device has demonstrated efficacy in five chronic sheep
      implantation studies of 14, 10, 28, 35, and 154 day duration. Post mortem
      findings from the 14 day experiment showed stable fibrin entangled around the
      impeller shaft and blades. After pump modification, autopsy findings of the 10
      day study showed no evidence of clot. Additionally, the results of the 28 day
      experiment showed only a small (2.0 mm) ring of fibrin at the shaft-seal
      interface. In the 35 and 154 day experiments, redesign of the stators have
      resulted in improved motor corrosion resistance. The 35 day study showed a small,
      0.5 mm wide fibrin deposit at the lip seal, but no motor failure. In the 154 day
      experiment, the motor failed because of stator fluid corrosion, while the
      explanted pump was devoid of thrombus. Based on these findings, the authors
      believe that these pump refinements have contributed significantly to
      improvements in durability and resistance to clot formation.

PMID- 8555620
TI  - Ventricular interaction in the pathologic heart. A model based study.
AB  - The effects of direct ventricular interaction and interaction mediated by the
      pericardium on the diastolic left ventricle (LV) were quantified using idealized
      models of five pathologic conditions. Two-dimensional (2D) mathematical models
      were constructed in long and short axis views of four pathologic LV conditions
      and the normal heart (NL): dilated cardiomyopathy (DCM), concentric LV
      hypertrophy (HYP), chronic anterior-apical infarction in a normal shaped LV
      (CAINL), and CAI in a dilated LV (CAID). To assess the effects of RV pressure
      increase on the LV mechanical state, RV pressure was systematically increased for
      several LV pressures and changes in the LV diastolic pressure-area relationships,
      and LV free wall and septal principal stresses and strains were quantified. At
      higher RV pressures, with pericardial effects included in the models, the
      pressure-area relationship was similar for all models, indicating that, at these
      higher pressures, the effects of RV and pericardial pressures are more important
      than global LV shape, wall thickness, or material properties in determining the
      pressure-area relationship. There were significant differences among models in
      the changes in LV free wall and septal stress and strain after an increase in RV
      pressure. These models may be of use in predicting interaction in the
      corresponding clinical state.

PMID- 8555621
TI  - Cardiovascular dysfunction. A rationale for characterization and a guide to
      therapy.
AB  - Traditional clinical assessment of cardiac function has relied on the indirect
      measurement of systemic blood pressure, heart rate and rhythm, and central venous
      pressure. However, because the circulation comprises complex interactions between
      flow and impedance in two hydraulic systems coupled in series, the usual
      assumptions drawn from the measurement of only a representative sample of this
      system can lead to serious errors in interpretation. This is particularly
      significant in conditions leading to physiologic distortions. Patients undergoing
      major surgery, or with suspected cardiac dysfunction, can only be adequately
      managed with a knowledge of both right and left heart pressures, together with
      the measurement of cardiac output. This report presents a rationale for the use
      of a simple method for interpreting these data and a guide to optimizing
      management. For those patients with heart failure who are unable to be sustained
      with conventional pharmacology, criteria are suggested that may help the
      clinician decide when more aggressive intervention, such as mechanical assist, is
      required.

PMID- 8555622
TI  - Secretory function of biohybrid pancreas devices containing isolated porcine
      islets.
AB  - Isolated porcine islets represent a potential source for discordant islet
      xenografts in diabetic patients. The authors therefore investigated insulin
      secretion from isolated porcine islets both in vitro and in vivo. For in vitro
      studies, islets were maintained in culture or placed in biohybrid perfusion
      devices consisting of a plastic housing containing a selectively permeable
      acrylic copolymer tubular membrane. Culture medium was circulated through the
      devices in a closed loop system. After 3 months the cultured islets secreted
      insulin at levels of 354 +/- 49 microU/equivalent islet number (EIN)/day (mean +/
      standard error of the mean [SEM]; n = 10). They responded to glucose stimulation
      (5 to 16 mmol/L steps) with significant increases in insulin secretion. The
      biohybrid devices seeded with islets produced 23 +/- 2 (mean +/- SEM; n = 8)
      units insulin per day over periods of 83 +/- 8 days. For in vivo studies, islets
      were sealed within membrane chambers and implanted in the peritoneal cavity of
      streptozotocin induced diabetic Lewis rats. Chambers with a total of 2 x 10(4)
      islets per rat normalized the plasma glucose values of 10 rats, with the
      concentrations decreasing from 487 +/- 18 to 97 +/- 10 mg/dl during the first
      month. All grafts maintained normoglycemia for longer then 3 months. Histologic
      studies of long-term chamber implants in rats (1-20 months of age) showed viable
      islets, with varying degrees of beta cell granulation. These studies suggest the
      long-term functioning of porcine islets both in vitro and in vivo as discordant
      xenografts.

PMID- 8555623
TI  - Relationship between stenting time and regeneration of neoesophageal submucosal
      tissue.
AB  - The authors developed a new type of artificial esophagus consisting of an inner
      silicone tube and an outer non antigenic collagen tube. The novel feature of this
      artificial esophagus is that the main part of the prosthesis is replaced by host
      tissue. In a previous study, the authors found that no stenosis of the artificial
      esophagus developed when the replacement part was stented for more than 4 weeks.
      It was considered that this stenosis was caused mainly by poor regeneration of
      submucosal tissue, rather than by the grade of reepithelialization. In this
      study, it was found that, in cases in which the stent dropped out within 3 weeks,
      fibrous tissue was noted beneath the neoesophageal epithelium. In such cases,
      neither muscle layers nor submucosal glands regenerated beneath the neoesophageal
      epithelium after replacement. However, in cases in which the stent dropped out
      more than 4 weeks after surgery, the neoesophagus was covered with a polylayer of
      squamous epithelium and had normal esophageal glands and a muscle layer.
      Therefore, it was concluded that muscle tissue and esophageal glands were able to
      regrow in the neoesophagus when the portion replaced by the artificial esophagus
      was stented for at least 4 weeks.

PMID- 8555624
TI  - End of life issues in ESRD. A study of three decision variables that affect
      patient attitudes.
AB  - The substantial end-stage renal disease (ESRD) mortality rate reflects an older
      population, worsening comorbidity, and increased cardiovascular disease. Advance
      directives in ESRD may simplify issues such as cardiopulmonary resuscitation
      (CPR) and dialysis discontinuation. However, ESRD patients with advance
      directives may change their mind or allow surrogate leeway for override of end-of
      life decisions. Three decision variables (requesting CPR, discontinuation of
      dialysis with depression, or discontinuation with dementia) were studied in 141
      ESRD patients through a 47 item questionnaire. Duration of dialysis (> or = 4
      years) (P = 0.002) and prior CPR experience (P = 0.02) increased the probability
      of refusing CPR by 12 times. The use of surrogates and substituted judgement for
      dialysis discontinuation with depression was more likely in women (P = 0.0006)
      and in patients with higher levels of education (P = 0.003). The odds of deciding
      to discontinue given dementia were three times greater for hemodialysis than
      peritoneal dialysis patients (P = 0.03). Eighty-three percent of the patients
      requested that physicians periodically check with them to determine if their
      advance directives had changed. The authors conclude that advance directives may
      assist ESRD patients, families, and staff with end-of-life decisions. Three end
      of-life decision variables are significantly affected by duration and type of
      dialysis, previous CPR, gender, and level of education.

PMID- 8555625
TI  - An artificial gill system for oxygen uptake from water using
      perfluorooctylbromide.
AB  - If the oxygen dissolved in seawater could be used for breathing, human beings
      could spend more time under water, greatly increasing their mobility. As yet,
      however, sufficient oxygen to enable us to live in the sea for long periods is
      not available. An artificial gill system has been developed for oxygen uptake
      from water to deoxygenated air using perfluorooctylbromide (PFOB), which has high
      oxygen solubility. It was found that oxygen was transferred rapidly from water to
      PFOB when water flowed outside the hollow fibers and PFOB flowed inside. Oxygen
      transfer through the membrane from PFOB to air was found to be the rate
      determining step. Use of PFOB gave a stable supply of oxygen from water to
      deoxygenated air over long periods. It was found that PFOB acts as a storage
      medium for oxygen.

PMID- 8555626
TI  - A new procedure for stable quantification of endotoxin in dialysate fluid using
      Limulus reagent.
AB  - For reliable determination of endotoxin, the activation of enzymes in lysate
      before measurement should be prevented, and the authors have designed a new
      procedure to effect this by dissolving the enzymes in lysate in a buffer solution
      of low pH. A given amount of the enzymes in lysate was dissolved in a lower pH
      buffer solution (pH 6.1-6.3) and the substrate was dissolved in a higher pH
      buffer solution (pH 8.0). After standing for 0-24 hr, both solutions were mixed
      with the sample solution. Data on blank absorbance and calibration line slope
      obtained by the new procedure were compared with those obtained by the
      conventional procedure. In the conventional procedure, blank absorbance increased
      with standing time, reaching approximately seven times the initial value in 24
      hr, whereas in the improved procedure, it increased by 1.5 times at a standing
      time of 3 hr, after which it was independent of standing time. The change in
      slope of the calibration line with standing time was more gradual in the improved
      procedure than in the conventional procedure. The authors conclude that the
      activation of enzymes in lysate can be prevented by dissolving the enzymes in a
      buffer solution of low pH, and that this procedure is effective for long-term
      monitoring of endotoxin concentration.

PMID- 8555627
TI  - Feasibility study of vascular-endoscopic valvuloplasty. Using a laser and
      flexible endoscope.
AB  - Percutaneous balloon valvuloplasty is generally accepted, but post procedural
      complications limit its efficacy and reduce long-term success. To eliminate these
      risks, the authors explored the feasibility of cardioscopy guided percutaneous
      laser valvuloplasty in an experimental setting. The combined working model
      consisted of a separate balloon tipped thin fiber optic endoscope, laser balloon
      catheter, and a Nd-YAG laser transmitter. A porcine pulmonary valve was used as
      our in vivo target of laser ablation in a beating heart. Under general
      anesthesia, the endoscopic catheter is delivered into the pulmonary valve area
      through either the internal jugular or femoral vein under fluoroscopy.
      Positioning the pulmonary apparatus coaxial to the endoscopic visual field by
      manipulation of the catheter allowed for targeting and ablation of the commissure
      of the pulmonary valve under endoscopic view through the balloon filled with
      saline solution. The ablation energy was 15-30 W, 0.5-1.0 sec, and 2,000-3,000 J
      total. The animal was then killed and histopathologic study of the ablated area
      was done. The commissure of the pulmonary valve was smoothly ablated in 4 cases,
      and the entire ablation procedure was successfully witnessed through endoscopy.
      The authors encountered some difficulty in laser targeting, limitations to the
      endoscopic field of vision, and difficulty in holding the position of the
      apparatus in the beating heart. These are the barriers to overcome for future
      clinical application of this procedure. However, these results indicate the clear
      possibility of future use of cardioscopy guided percutaneous laser valvuloplasty
      in a clinical setting.

PMID- 8555628
TI  - The response of various hematologic parameters in the young bovine subjected to
      multiple phlebotomies.
AB  - Specific guidelines for the optimal collection of blood from calves maintained as
      donors do not exist. This investigation was conducted to document erythrocytic
      changes in calves subjected to controlled blood loss. Two groups of Holstein
      calves ranging in age from 2 to 5 months were compared. Six animals were
      designated controls and six were subjected to a series of three blood collections
      over an 8 day period. Each collection was roughly 50% of the total circulating
      blood volume (30 ml/kg of body weight). Hematologic values were compared for 18
      days. All calves survived the study. There was no significant difference in
      circulating cortisol levels or growth rate between groups. Packed cell volumes
      (PCVs) for the phlebotomized group did not return to original levels during the
      monitoring period (initial 36%, final 26%), but were within normal limits at 30
      days. All phlebotomized calves had a high reticulocyte count (0% control, 11%
      phlebotomized). Reticulocytes were not observed until the PCV fell below 20. HbF
      to HbA ratios were a sensitive and acute indicator of accelerated erythropoiesis.
      Variant ratios stabilized within 18 days. Other parameters compared were red cell
      indices, total erythrocyte count, total leukocyte count, total plasma protein,
      total hemoglobin values, and neutrophil to lymphocyte ratios.

PMID- 8555629
TI  - Simultaneous evaluation of cardiac wall motion and myocardial ischemic injury by
      measurement of electrical impedance.
AB  - The authors devised a new method to simultaneously evaluate cardiac wall motion
      and myocardial ischemic injury by measurement of myocardial electrical impedance.
      This method is based on the principle that electrical properties of the
      myocardium are affected by intra- or extracellular structure. Impedance was
      assessed by measuring voltage while a constant alternating current (0.4 mA, 50
      kHz) was being applied to the myocardium by way of an electrode that had two
      parallel 6 mm long needles. In five dogs, an electrode was placed in the left
      ventricular wall, adjacent to a pair of ultrasonic crystals that were used to
      estimate regional wall thickness. To change regional contractility and to induce
      ischemic injury, the left anterior descending coronary artery was ligated. The
      impedance waveforms were observed to be synchronized with cardiac contraction,
      and changes in impedence correlated well with changes in wall thickness.
      Dyskinetic movements in the ischemic myocardium could also be detected through
      assessment of the impedance waveform. During the first 2 hr, the average value of
      impedance increased significantly, from 254 +/- 38 omega-cm to 329 +/- 13 omega
      cm (P < 0.005), and then decreased, indicating a correlation with the progression
      and irreversibility of ischemic injury. This simple technique may eventually
      allow us to simultaneously assess cardiac wall motion and myocardial ischemia in
      humans.

PMID- 8555630
TI  - An internal thoracic artery homograft as a new small caliber vascular substitute.
AB  - The authors have examined the possibility of usage of an internal thoracic artery
      (ITA) homograft as a new small caliber vascular substitute. Left subclavian
      artery to left atrial appendage shunts with fresh ITA homografts (n = 6) or ITA
      autografts (n = 5) were made by modified techniques of coronary artery bypass
      grafting in mongrel dogs (body weight, 11-16.5 kg). All recipient dogs had no
      anticoagulant therapy or immunosuppression. Inner diameter of the grafts was
      between 1.4 and 2.0 mm. Blood flow in ITA grafts was measured by electromagnetic
      flow meter. The graft flow was 6-14 ml/min before harvest and 67-220 ml/min just
      after implantation, and there was no significant difference between groups. Flow
      in the ITA homografts decreased significantly compared with ITA autografts 1
      month after operation, but five of six ITA homografts were patent. Histopathology
      of the grafts showed vascular rejection in the homograft group. These results
      suggest that an ITA homograft with postoperative immunosuppression might be a new
      small caliber vascular substitute for coronary artery bypass grafting in ischemic
      heart disease and the systemic-pulmonary shunt operation in congenital heart
      diseases.

PMID- 8555631
TI  - Experimental reconstruction of the intrathoracic trachea using a new prosthesis
      made from collagen grafted mesh.
AB  - Intrathoracic tracheal replacement was performed in dogs using a tracheal
      prosthesis we had constructed from mesh. The prosthesis consists of Marlex mesh
      (polypropylene) reinforced with a continuous polypropylene spiral, and is grafted
      and coated with pig collagen (Types I and III). Complete surgical resection of
      the mediastinal trachea was performed in seven adult mongrel dogs. In 1 dog, a 4
      tracheal ring segment (2 cm) was resected and replaced with a 3 cm prosthesis,
      and in 6 dogs, a 7 to 8 tracheal ring segment (4 cm) was resected and replaced
      with a 5 cm prosthesis. In the latter six dogs, a silicone tube was temporarily
      inserted into the replacement, and removed by bronchoscopy one month after
      surgery. In one dog that received a 4 cm replacement, we added omentopexy around
      the reconstructed trachea. The prostheses in all dogs were promptly infiltrated
      by surrounding tissue and incorporated by the host trachea. No dehiscence or air
      leakage was observed after surgery. Mild luminal stenosis was evident in one dog,
      and partial exposure of the mesh (ulceration) was observed in five dogs within an
      observation period of 3 to 26 months. However, in the dog that received
      omentopexy after tracheal reconstruction, no stenosis or ulceration was observed,
      and the luminal surface seemed lustrous even after 6 weeks. Formation of
      respiratory epithelium, which lined the prosthetic lumen, was seen to various
      degrees: in the 2 dogs killed 12 months and 26 months after surgery, confluent
      epithelization was confirmed histologically from the upper to the lower
      anastomosis of the prosthesis. The tracheal prosthesis is useful for the repair
      of intrathoracic tracheal defects and shows promise for clinical application with
      further investigation.

PMID- 8555632
TI  - Immobilization of human thrombomodulin onto biomaterials. Comparison of
      immobilization methods and evaluation of antithrombogenicity.
AB  - Human thrombomodulin (hTM), which is a newly described endothelial cell
      associated protein that functions as a potent natural anticoagulant by converting
      thrombin from a procoagulant protease to an anticoagulant, was immobilized on to
      various substrates by two immobilization methods. As the substrates of
      immobilization, poly(acrylic acid) surface grafted poly(ethylene) (PAAc-g-PE)
      film, poly(vinylamine) surface grafted poly(ethylene) film, and PAAc surface
      grafted nylon were used. For immobilization, simultaneous preactivation methods
      were used. The effect of the immobilization reaction on hTM activities, the
      comparison of the activities of immobilized hTM with those of free hTM, and the
      effect of the thrombin incorporation on antithrombogenic activity were studied.
      The hTM immobilized onto PAAc-g-PE by preactivation showed the highest
      antithrombogenic activity. The thrombin incorporation affected protein C
      activation activity but not the fibrinogen clotting time. hTM immobilized nylon
      showed greater antithrombogenicity in vitro.

PMID- 8555633
TI  - A new, cryoprecipitate based coating for improved endothelial cell attachment and
      growth on medical grade artificial surfaces.
AB  - Monoprotein coatings of biomaterials with either natural adhesion molecules or
      genetically designed analogs have been used to facilitate attachment and
      spreading of endothelial cells. However, such treatments were found insufficient
      to maintain the integrity of the endothelial surface under turbulent flow
      conditions. In addition, when brought into contact with blood, these coatings
      were susceptible to plasma and cell proteinases that could readily destroy their
      structure and weaken cell adherence to the surface. In addressing these problems,
      we developed a cryoprecipitate-based coating that can firmly bind to any
      nonporous, prosthetic surface and interact with endothelial cells. The primary
      structure of the coating consisted of an autologous fibrin meshwork. It was
      refined by various compositions of the fibrinogen containing mixture and secured
      to polystyrene or polyurethane surfaces by dry-heat treatment. Further modulation
      of the coating was achieved by physically immobilizing various doses of heparin
      and insulin into the three dimensional matrix of the meshwork. Endothelial cells
      attached and grew much better on polyurethanes coated with this autologous
      protein complex than on a polystyrene tissue culture surface. With proper use of
      its capacity to mimic the properties of basal membrane, and absence of
      immunologic complications, the resulting coating may become an ideal
      multifunctional interface between cells and prosthetic materials.

PMID- 8555634
TI  - Biocompatible surfaces using methacryloylphosphorylcholine laurylmethacrylate
      copolymer.
AB  - Many materials used in the medical device industry were not originally developed
      for these applications. In general, these materials elicit adverse biologic
      responses when in contact with body fluids such as blood, and the mechanisms of
      the response of blood to an artificial surface are well characterized. Protein
      adsorption, platelet adhesion, and activation of the coagulation pathway can
      subsequently lead to thrombus formation with grave clinical consequences in the
      absence of anticoagulant. However, the use of anticoagulants can result in
      complications. In recent years various approaches for overcoming these problems
      by improvement of the biocompatibility of materials have been advocated. One
      approach is that of biomembrane mimicry, whereby the surface of a material is
      coated with a derivative of phosphorylcholine (PC). PC is the major lipid head
      group component found in the outer surface of biologic cell membranes. In this
      paper, the application of PC coatings to a range of materials is discussed
      together with characterization of the surfaces using in vitro biocompatibility
      tests. Studies of fibrinogen and platelet binding have shown significant
      reductions in adsorption of these components to various PC coated materials
      relative to uncoated controls. Materials tested, amongst others, include PVC,
      polyethylene, polycarbonate, and nylon. The stability of the PC coatings has been
      studied using radiolabeled derivatives. Results using several materials show that
      physiadsorbed PC coatings are extremely stable, thus making the coatings suitable
      for use in a wide variety of medical applications. Extensive biologic evaluations
      to assess the toxicologic profile of PC derivatives and coated devices have also
      been carried out and in all tests the materials have been shown to be nontoxic,
      thus making them suitable for human use. Ex vivo animal and human studies
      performed support the in vitro data.

PMID- 8555635
TI  - Endothelial cell binding to Dacron modified with polyethylene oxide and peptide.
AB  - Polyethylene oxide (PEO) was incorporated into the surface of Dacron (PET)
      vascular prosthetic material (crimped Bionit I, BNl) followed by covalent
      attachment of an endothelial cell (EC) adhesion peptide; Gly-Arg-Glu-Asp-Val-Tyr
      (GREDVY). This procedure provides the possibility of a surface selective for EC
      adherence. Optimal PEO incorporation with minimal fiber damage was achieved from
      78% (vol) trifluoroacetic acid (TFA) as characterized by scanning electron
      microscopy, nuclear magnetic resonance, bromphenol blue staining, and tensile
      testing. By weight, there was 4.4 times as much 18.5kD PEO as 1.5kD PEO
      incorporated into PET, but there were 2.8 times as many molecules of low
      molecular weight PEO. Attachment of 125I-GREDVY to substrates increased as
      follows: BNJ < BNI - 18.5 kD PEO < BNI - 1.5 kD PEO. Polyethylene oxide size
      affected EC binding with high molecular weight material decreasing binding and
      low molecular weight PEO increasing attachment. GREDVY modification of BNI or
      either of the two BNI-PEOs gave small but consistently increased EC binding
      compared with the same preparation without GREDVY. In contrast, human fibroblasts
      cultured from umbilical vein showed decreased binding when GREDVY was attached to
      BNI or PEO modified BNI. These results indicate that selective EC binding to PET
      vascular prostheses can be achieved.

PMID- 8555636
TI  - A two layer model for the effects of blood contact on membrane transport in
      artificial organs.
AB  - The performance of many artificial organs can be strongly affected by the
      transport characteristics of the semi-permeable membranes used in these devices,
      but there is little data on the effects of blood contact on membrane transport
      properties. Experimental data were obtained for the solute flux through
      cellulosic, polyacrylonitrile, and polyethersulfone membranes using polydispersed
      dextrans. Blood contact had a very large effect on diffusive solute transport
      through the asymmetric polyethersulfone membranes, but only a small effect on
      diffusion through the symmetric AN69 and Cuprophan membranes. In contrast, blood
      contact caused a similar reduction in convective solute transport (sieving)
      through both the polyethersulfone and AN69 membranes. Convective transport
      through the blood contacted membranes was also dependent on the flow direction,
      with greater transport obtained when the membrane was oriented with the blood
      contacted surface downstream. These data were analyzed using a two layer membrane
      model consisting of an upper layer of blood cells and proteins adsorbed to the
      surface of the native membrane. This model accurately accounted for the different
      effects of blood contact on convection and diffusion, as well as the observed
      asymmetry in convective solute transport. These results have important
      implications for the analysis of solute transport in artificial organs.

PMID- 8555637
TI  - The benefits of fluoropassivation of polyester arterial prostheses as observed in
      a canine model.
AB  - The effect of treating the surface of a polyester vascular prosthesis with a
      novel fluoropolymer before sealing the graft with gelatin has been evaluated in a
      canine thoracoabdominal bypass model. The healing behavior of the Fluoropassiv
      graft was compared with that of the Gelsoft ERS prosthesis used as control for
      prescheduled periods of implantation ranging from 4 hr to 6 months. Both series
      of explanted grafts were analyzed using macroscopic, histologic, and scanning
      electron microscopic observations, and by determining the
      prostacyclin/thromboxane A2 ratio (PGI2/TXA2) and the thrombogenicity of the
      luminal surface by means of labelled platelets and fibrin deposition. Chemical
      analysis of explanted and cleaned graft segments was performed using electron
      spectroscopy for chemical analysis, differential scanning calorimetry, and
      contact angle methods. No difference in platelet and fibrin deposition or
      PGI2/TXA2 secretion by the luminal surface was observed between the treated and
      the control grafts at any implantation period. On the other hand, pathologic
      investigation has revealed that, although there is no difference between the two
      grafts during the first month, the healing sequence of the Fluoropassiv graft
      appeared more complete and mature than the control graft after 3 and 6 months.
      Differences were observed in the extent of collagenous internal capsular
      development, endothelialization, and tissue penetration into the knitted
      structure. The presence of fluorine and a higher contact angle at the surface of
      all the explanted fluoropassivated grafts is believed to have been responsible
      for reducing the inflammatory response and enhancing the long-term healing
      behavior of this novel prototype device over the control gelatin sealed
      prosthesis.

PMID- 8555638
TI  - Erythropoietin response to blood loss in hemodialysis patients in blunted but
      preserved.
AB  - In anemic non-renal and hemodialysis (HD) patients, erythropoietin (EPO) levels
      vary > 10 fold at any hematocrit (Hct), suggesting marked variation in endogenous
      EPO production among individuals. We hypothesized that this intrinsic variation
      that reflects differences in bone marrow sensitivity to circulating EPO could
      account for the > 10 fold variability in recombinant human erythropoietin
      (rHuEPO) requirements of HD patients to correct their anemia, and could be
      evaluated by examining the response to blood loss and measurement of red blood
      cell (RBC) survival (tau). The renal response to blood loss was studied in normal
      patients (N = 14) and in non-rHuEPO treated HD (n = 12) patients by measuring the
      increase in EPO (delta EPO) above basal level. Serum samples were obtained before
      and after the blood loss event. Delta EPO after a one-unit phlebotomy was larger
      in normal patients than in HD patients, although delta Hct was larger in HD.
      Regression of delta EPO against Hct/erythropoietin basal level, an index of bone
      marrow sensitivity, indicated parallel responses in normal and HD subjects, with
      the magnitude of response decreased in HD. To exclude an effect of a difference
      in RBC survival between control and end-stage renal disease (ESRD) patients, we
      measured more than 16 other patients (Hct 24.1) that averaged 107 days (range 70
      140) and were independent of Kt/V (mean 1.01; range 0.67-1.38). Intersubject
      differences in bone marrow sensitivity to EPO exist and are detected by delta EPO
      after blood loss. Response of delta EPO to blood loss is diminished, but not
      abrogated, by renal disease.

PMID- 8555640
TI  - Hepatitis C transmission through dialysis machines.
AB  - Hepatitis C virus antibodies (HCVAb) were studied in a total of 58 patients on
      chronic hemodialysis, all of whom were negative for Hepatitis B serology. The
      patients were evaluated by the second generation EIA test. Twenty-one of these
      patients, initially HCVAb(-), were dialyzed in unit A (UA), where no patients
      HCVAB(+) were ever dialyzed nor were patients with increased levels of serum
      transaminases, although they were HCVAb(-). Thirty-seven patients, also initially
      HCVAb(-), were dialyzed in unit B (UB), where they shared the same dialysis
      machines (DM) with 14 HCVAb(+) and 11 HCVAb(-) with elevated serum transaminases
      patients. Time on hemodialysis for UA patients was 30.95 +/- 10.74 months (range
      14-52 months). In UB patients, time on dialysis was 28.46 +/- 17.33 months (range
      4-78 months) (P = 0.554). The seroconversion for patients who were initially
      HCVAb(+) was: in UA, none became (+); and in UB, 17 patients became (+); Chi
      square = 11.522 (P < 0.0001). Ten patients were transfused in UA and 23 in UB
      (Chi-square = 0.638; P = 0.424). In addition, 2.30 +/- 1.5 blood units were given
      to patients transfused in UA and 2.09 +/- 1.65 were given to patients transfused
      in UB (P = 0.733). This data indicates the existence of a route of vertical
      transmission from patient to patient through the DM, which would explain the
      differences between these two groups.

PMID- 8555639
TI  - Pharmacomechanical thrombolysis with urokinase for treatment of thrombosed
      hemodialysis access grafts. A comparison with surgical thrombectomy.
AB  - Seventy-one consecutively occluded polytetrafluoroethylene (PTFE) grafts treated
      with pharmacomechanical thrombolysis were compared with 75 surgical controls. The
      patients undergoing thrombomechanical lysis had a comparable rate of successful
      declotting (91% vs. 90.7%) and no significant difference in patency at 24 and 48
      hr, 1 week, and 1 and 6 months. Patients undergoing thrombolysis required less
      overnight hospitalization (17 vs. 82%) (P < 0.001) and their hospital stays
      averaged 1.03 days versus 3.43 days in the surgical thrombectomy group (P <
      0.0001). Complication rates were similar in both groups. Hospital charges and
      physician fees were significantly lower in the thrombolysis group, with total
      charges averaging $6,802 versus $12,740 (P = 0.0018). These cost differences were
      maintained even when patients with extended stays were excluded. In conclusion,
      pharmacomechanical thrombolysis provides efficacy and complications comparable to
      surgical thrombectomy, with the benefits of a decreased rate of hospitalization,
      decreased total number of days of hospitalization, and significant cost savings.
      The authors determined that pharmacomechanical thrombolysis is the preferable
      first intervention for acutely occluded PTFE grafts.

PMID- 8555641
TI  - Reproducibility of the peritoneal equilibration test in CAPD patients.
AB  - A study was undertaken to evaluate the short-term reproducibility of peritoneal
      equilibration test (PET) results. Nine patients with end-stage renal disease
      undergoing continuous ambulatory peritoneal dialysis underwent PETs under similar
      conditions on 2 consecutive days. Dialysate samples were obtained at 0 hours,
      midcycle, and at the end of exchange. There were no significant differences
      between the mean ratios at 4 hours for creatine, urea nitrogen, potassium and
      protein, and glucose between PET 1 and PET 2. A standard PET is highly
      reproducible when repeated under similar conditions. Reproducibility is better
      for ratios of creatinine, glucose, urea nitrogen, and potassium than for protein.

PMID- 8555642
TI  - Pulsed laser deposition of thin film hydroxyapatite. Applications for flexible
      catheters.
AB  - Skin exit site infections are a major source of morbidity in patients with
      indwelling percutaneous catheters. Ceramic materials, such as hydroxyapatite (HA)
      and alumina, have demonstrated excellent biocompatibility and low rates of
      infection in soft tissues. Previous attempts to design ceramic materials for use
      as percutaneous connectors have resulted in rigid discs or solid cylindrical
      tubes. In order to take advantage of the inherent properties of HA without
      reducing patient comfort or mobility, the feasibility of applying a thin film of
      HA directly onto a flexible polymeric catheter was studied. The coating was
      applied by pulsed laser deposition (PLD). The beam from a KrF excimer laser
      impinged upon a target of pressed and sintered HA, producing a plume of ablated
      material that was deposited onto the catheter tubing. By rotating the tubing, an
      even coating of HA was applied to the catheter at a thickness of approximately
      0.50 microm. The coating did not compromise the flexibility of the catheter
      tubing. Hence, PLD of a thin film of HA at the exit site of percutaneous
      catheters may be a means of incorporating the bioactive and biocompatible
      properties of HA with the mobility and patient comfort that characterize
      polymeric catheters.

PMID- 8555643
TI  - Effects of euhydric peritoneal dialysis solutions containing mixture of
      bicarbonate and lactate or lactate alone on neutrophilic superoxide production.

PMID- 8555644
TI  - Innovative ventricular assist systems.

PMID- 8555645
TI  - Telomere dynamics and telomerase activation in tumor progression: prospects for
      prognosis and therapy.
AB  - Eukaryotic telomeres provide a reservoir of redundancy to compensate for
      incomplete replication of chromosome ends. In multicellular eukaryotes, they are
      eroded by a varying number of base pairs at every cell division. When telomere
      repeats are critically shortened, DNA damage response pathways involving p53 (and
      in some cell types retinoblastoma protein) are invoked, leading to "M1
      senescence" in normal cells; cancer cells, which frequently lack normal p53 and
      RB functions, often develop chromosomal instability leading to telomeric
      associations, ring chromosomes, and breakage-fusion-bridge cycles. These
      consequences of telomere erosion exert selection pressure for activation of the
      ribonucleoprotein enzyme telomerase, which adds new telomeric repeats at
      chromosome ends, and in vertebrates normally is active only in the germ line and
      the early embryo. Somatic cells that reactivate telomerase in vitro or in vivo
      become immortal. Telomerase activity has been found in many advanced and
      metastatic human cancers, suggesting that telomerase-dependent M2 immortalization
      may contribute to metastatic potential. When mammalian telomerases are isolated
      and their genes cloned and sequenced, the localization of telomerase expression
      in tumors may provide prognostic indicators of metastatic potential. The
      abrogation of telomerase function by pharmacological inhibition, genetic
      disruption, or repression of gene expression is a potential avenue of
      antimetastatic therapy.

PMID- 8555646
TI  - Plasminogen activator activities in short-term tissue cultures of benign
      prostatic hyperplasia and prostatic carcinoma.
AB  - The high prevalence of prostatic carcinoma (PRCA) and the limited therapeutic
      possibilities provide a strong stimulus for exploring new approaches in
      experimental research that ultimately may lead to improved therapy. Indeed,
      methods for assessing carcinoma prognosis, such as clinical staging (clinical
      examination, ultrasound, and plasmatic levels of prostatic acid phosphatase and
      prostate specific antigen) and histopathological grading according to the Gleason
      score, usually fail to provide consistent predictive information regarding the
      clinical outcome of single tumors. Increased plasminogen activator (PA)
      activities have been associated with high-grade malignancies and with the
      potential for invasion/metastasis in many tumors. Urokinase-type plasminogen
      activator (uPA) is present in prostatic secretion, and an increased uPA activity
      has been noted in human prostatic cell lines with metastatic behavior.
      Unfortunately, any study of uPA production or gene regulation in primary tumors
      is complicated by the inherent mixture of host stromal cells, infiltrating
      macrophages, and subpopulations of tumor cells that may have variable metastatic
      capacity and ability to synthesize uPA. In short-term tissue culture of prostatic
      samples, it is possible to grow in vitro cancer prostatic epithelial cells and
      thus exclude the presence of contaminant cells. We have shown elsewhere that the
      levels of a type IV collagenase, 92-kDa matrix metalloproteinase, a protease
      involved in tumor progression and invasion, are increased in PRCA primary cell
      cultures if compared with benign prostatic hyperplasia (BPH) cell cultures (C.
      Festuccia et al., manuscript in preparation). Activation of matrix
      metalloproteinases also can be correlated with uPA expression; therefore we
      studied the expression of uPA in serum-free culture media of primary cultures of
      PRCA or BPH tissue samples.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8555647
TI  - Thymosin fraction 5 does not influence urinary tract carcinogenesis by phenacetin
      and N-butyl-N-(4-hydroxybutyl)nitrosamine in NON/Shi mice.
AB  - The effect of thymosin fraction 5 (TF5) on the promotion and progression phases
      of urinary tract carcinogenesis induced by consecutive administration of
      phenacetin and N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in NON/Shi mice was
      investigated. The study was carried out twice with a minor modification to the
      protocol in the second experiment. Fifty-seven male NON/Shi mice in experiment 1
      and 100 mice in experiment 2 were each divided into four groups. Phenacetin was
      administered for 8 weeks in experiment 1 and 12 weeks in experiment 2, and
      subsequently BBN was given for 6 weeks in both cases, for total observation
      periods of 30 and 34 weeks, respectively. Sixty micrograms of TF5 per mouse was
      inoculated subcutaneously twice a week during (group 2) or after (group 3) BBN
      exposure, or both periods (group 4). Group 1 served as a control group without
      TF5 treatment. Histopathological examination revealed no effects on either
      induction of urinary tract carcinomas or distant metastasis from renal pelvic
      carcinomas in either experiment.

PMID- 8555648
TI  - The steroidogenic and morphological effects of paclitaxel on cultured ovarian
      cancer cells.
AB  - We have studied the biochemical effects of paclitaxel (trade name Taxol) in three
      ovarian cancer (OV Ca) cell lines and JEG-3 choriocarcinoma cells. Paclitaxel (1
      microgram/ml) was cytotoxic to approximately 80% of OV Ca cells, and the ED50
      ranged from 6 to 9 ng/ml. Paclitaxel was also cytotoxic to JEG-3 cells (ED50 40
      ng/ml), but even at 1 microgram/ml, 40-50% of the cells survived paclitaxel
      treatment. Paclitaxel increased 17 beta-estradiol secretion 3-4 fold in all three
      OV Ca cell lines with an ED50 range of 3-13 ng/ml. Similarly, paclitaxel
      increased estradiol secretion from JEG cells with an ED50 of 50 ng/ml. Colchicine
      also increased estradiol secretion significantly from OV Ca cells at 2 microM
      while reducing cell number approximately 40% (beta-lumicolchicine, an inactive
      isomer, was ineffective at this concentration). Paclitaxel (1 microgram/ml)
      treatment of BR OV Ca cells produced alterations in morphology leading to
      "rounding" of cells within 6 h of treatment. Simultaneously, paclitaxel increased
      immunohistochemical staining for aromatase, and this increase was coincident with
      morphological alterations. The present results demonstrate that low
      concentrations of paclitaxel can have significant steroidogenic, as well as
      cytotoxic, effects on OV Ca cells, suggesting that paclitaxel may activate signal
      transduction pathways in addition to disrupting microtubule function. These
      findings further suggest that paclitaxel could be efficacious at submicromolar
      concentrations.

PMID- 8555649
TI  - IL-10 blocks collagen IV invasion by "invasion stimulating factor" activated PC-3
      ML cells: upregulation of TIMP-1 expression.
AB  - We have previously shown that a 78-kDa "invasion stimulating factor" (ISF)
      triggers collagenase IV (MMP-2) secretion and the invasive behavior of metastatic
      PC-3 ML subclones in modified Boyden chamber assays [Stearns, M. E.; Stearns, M.
      Autocrine factors, type IV collagenase secretion and prostatic cancer cell
      invasion. Cancer Metastasis Rev. 12:39-52; 1993. Wang, M.; Stearns, M.; Stearns,
      M. E. Identification of the receptor for a novel M(r) 78,000 "invasion
      stimulating factor" from metastatic human prostatic PC-3 ML clones. Cancer Res.
      54:2492-2495; 1994.]. Recently, we have shown that interleukin 10 (IL-10)
      preferentially stimulates tissue inhibitor of metalloproteinase-1 (TIMP-1)
      production in these cells [Wang, M.; Stearns, M. E. Characterization of a novel
      TIMP-1 enhancer element. J. Biol. Chem., submitted.]. In this paper, we report
      that IL-10 (20-40 ng) can inhibit the invasion stimulatory effects of ISF (30-60
      ng) on PC-3 ML cells. "Checkerboard analysis" with modified Boyden chambers
      (precoated with 10 and 100 micrograms collagen IV) shows that IL-10 inhibits the
      stimulatory effects of ISF on both cell motility and chemoinvasion processes. In
      support of these data, exogenously supplied TIMP-1 (10 micrograms/ml) and
      collagenase antibodies (1:200 dilution) both completely blocked invasion.
      Quantitative ELISAs comparing the molar ratios of TIMP-1:MMP-2 and TIMP-2:MMP-2
      further demonstrate that IL-10 (10-40 ng) preferentially activates TIMP-1
      secretion to increase the molar ratio of TIMP-1:MMP-2 in the presence of
      increasing amounts of ISF (0-60 ng). IL-10 did not elevate TIMP-2 secretion or
      influence the molar ratio of TIMP-2:MMP-2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8555650
TI  - Experimental study on safety for granulopoiesis in simultaneous therapy with
      recombinant human granulocyte colony-stimulating factor and chemotherapy.
AB  - Since recombinant human granulocyte colony-stimulating factor (rhG-CSF) recruits
      hematopoietic progenitor cells into the cell cycle, the possibility remains that
      simultaneous injection of rhG-CSF and chemotherapeutic agents may aggravate the
      chemotherapy-induced neutropenia by sensitizing normal progenitor cells to the
      cytotoxic effects of chemotherapeutic agents. Therefore, the use of rhG-CSF is
      usually restricted from the day after chemotherapy. In the present study, we
      investigated whether concurrent treatment with rhG-CSF and chemotherapeutic
      agents aggravated granulopoietic failure, using murine neutropenic models.
      Neutropenia induced by a single injection of cyclophosphamide, mitomycin C,
      adriamycin, vincristine, combination of mitomycin C+vincristine, or combination
      of cyclophosphamide+vincristine+adriamycin (CHOP) was not aggravated by
      simultaneous injection of rhG-CSF (30 micrograms/kg, SC). In contrast, a single
      concurrent injection of rhG-CSF and 5-fluorouracil aggravated the neutropenia and
      the decrease in marrow colony-forming unit-granulocyte/macrophage counts, but
      simultaneous and following injections of rhG-CSF enhanced the recovery of
      neutrophils. Moreover, neutropenia induced by successive treatment with cisplatin
      was prevented by concurrent treatment with rhG-CSF during the period of the
      chemotherapy. From these results, concurrent treatment with rhG-CSF and
      chemotherapeutic agents with the exception of 5-fluorouracil may be feasible and
      well-tolerated in clinical use.

PMID- 8555651
TI  - Cytokine (IL-10, IL-6) induction of tissue inhibitor of metalloproteinase 1 in
      primary human prostate tumor cell lines.
AB  - Northern blots and scintillation counting showed that tissue inhibitor of
      metalloproteinase 1 (TIMP-1) mRNA was expressed by low passage, primary
      epithelial cultures (n = 5) of low-grade human prostatic carcinoma. TIMP-1 mRNA
      levels were normally low in the primary cell lines, but were inducible by
      interleukin (IL) 10 and 6. Dose and time-course studies indicated that IL-10 was
      the most potent stimulator of TIMP-1 expression. Cycloheximide blocked the
      effects of IL-10 in a reversible manner. In situ hybridization assays with TIMP-1
      oligonucleotide antisense probes confirmed the northern blot results and
      indicated that IL-10 preferentially stimulated TIMP-1 mRNA synthesis. We suggest
      that IL-10, and to a lesser extent IL-6, may normally influence TIMP-1 expression
      by human prostatic epithelial cells.

PMID- 8555652
TI  - Cell cycle inhibition of HTLV-I transformed T cell lines by retinoic acid: the
      possible therapeutic use of thioredoxin reductase inhibitors.
AB  - Adult T cell leukemia derived factor (ADF), which was first reported as a
      cytokine-like factor produced by human T lymphotropic virus I (HTLV-I)
      transformed T cells, is a human homologue of thioredoxin (TRX). ADF/TRX has
      multiple functions including growth promoting, antiapoptotic and radical
      scavenging activities, and is also involved in a wide variety of intracellular
      processes as a dithiol reducing agent in cooperation with the NADPH-TRX reductase
      system. In HTLV-1(+) T cell lines, HuT 102 and MT-2, which are ADF/TRX high
      producing cells, we found that the expression of ADF/TRX was dependent on the
      cell cycle and peaked at S phase. The reducing activity of ADF/TRX in these cells
      was also dependent on the cell cycle and elevated in S phase as determined by
      NADPH-dependent insulin degradation assay. Furthermore, inhibitors of TRX
      reductase, 13-cis-retinoic acid (13-cis-RA) and azelaic acid, inhibited the DNA
      synthesis of these cells. In contrast, the residual expression and reducing
      activity of ADF/TRX in HTLV-I(-) T cell lines did not show any significant
      correlation with the cell cycle. There was no distinct inhibitory effect of 13
      cis-RA or azelaic acid on the growth of these ADF/TRX low producing cells. These
      results indicate that a high level of reducing activity of the ADF/TRX system may
      be required for the cell division of these virally transformed cells. This
      suggests that the TRX reductase inhibitors including retinoid derivatives have a
      potential therapeutic utility for treatment of HTLV-1(+) T cell leukemia without
      any effect on HTLV-I(-) cells.

PMID- 8555654
TI  - Reference listings in cancer research.

PMID- 8555653
TI  - Combined effects of buthionine sulfoximine and cepharanthine on cytotoxic
      activity of doxorubicin to multidrug-resistant cells.
AB  - We studied the potentiation of doxorubicin (DOX) activity in multidrug-resistant
      (MDR) cells by buthionine sulfoximine (BSO), a specific inhibitor of gamma
      glutamylcysteine synthetase, and by cepharanthine (CE), which interacts with P
      glycoprotein. The glutathione (GSH) of MDR cells was approximately 1.5-fold
      greater than that of the parental cell line. BSO reduced GSH content of MDR cells
      compared to that of the sensitive ones. The BSO treatment (50 microM) enhanced
      the effect of DOX by 1.8-fold, while CE caused a greater reversal of drug
      resistance. The combination of BSO with CE produced further potentiation of DOX
      activity in an antiproliferative effect. Pretreatment of cells with BSO did not
      alter the cellular accumulation of DOX in the absence or presence of CE. The
      addition of BSO (30 mM) to the drinking water of mice reduced the tissue levels
      of GSH in tumor cells, suggesting that the marked decrease in GSH might diminish
      the ability of that tumor to resist DOX. Combined administration of CE and DOX
      resulted in enhancement of DOX antitumor activity and prolongation of survival
      time. The survival of mice treated with BSO and CE as a supplement to DOX
      treatment was superior that of mice receiving DOX alone. These studies
      demonstrated that the combinations of BSO with CE may be useful for killing drug
      resistant tumor cells.

PMID- 8555655
TI  - 6th Meeting of the Neurosonology Research Group of the World Federation of
      Neurology. Salzburg, Austria, September 1-3, 1995. Abstracts.

PMID- 8555656
TI  - Clinical cerebrovascular applications of arterial ultrasound volume flow rate
      estimates.
AB  - A variety of disorders affect cerebral hemodynamics. Volume flow rate (VFR)
      estimates now allow accurate quantification of the effect of cerebrovascular
      lesions on the conduit vessels, with excellent in vivo and in vitro correlation.
      Four selected cases with VFR data and angiographic correlation are presented to
      illustrate potential clinical uses of this method. The VFR estimates were
      obtained with a color M-mode-based velocity imaging technique, which uses time
      domain processing (P-700 Color Velocity Imaging System, Philips Ultrasound
      International, Irvine, CA). In a patient awaiting coronary artery surgery, with
      unilateral internal carotid artery occlusion and contralateral angiographic
      stenosis (50-80%, reader variation), the baseline and acetazolamide-challenged
      common carotid artery VFRs showed excellent conduit function ipsilateral to this
      stenosis. Thus, the angiographic stenosis did not have significant hemodynamic
      effects and endarterectomy was avoided. In a patient with an arteriovenous
      malformation fed by the left vertebral and left external carotid arteries, high
      in the left cervical region, VFR estimates of two to three times normal predicted
      the feeding vessels, influenced management, and proved helpful in follow-up. In a
      patient with subclavian steal syndrome, VFR estimates quantified the steal after
      brachial hyperemia. Finally, in a patient with delayed vasoconstriction after
      subarachnoid hemorrhage, very low VFR estimates preceded clinical deterioration.
      Quantification of hemodynamic changes with VFR estimates was useful for the
      diagnosis, management, and follow-up of these patients with four types of
      cerebrovascular disease, and should be applicable in many others.

PMID- 8555657
TI  - Interrater agreement of computed tomography infarct measurement.
AB  - To determine the reliability of infarct measurements on hard-copy computed
      tomography (CT) images the in vivo (IV) infarct volumes of 20 CT-detected
      infarcts were estimated and divided into four size groups with 5 infarcts in each
      group: Group A, less than 0.5 ml; Group B, 0.5 to 5.0 ml; Group C, 5 to 50 ml;
      and Group D, more than 50 ml. Seventeen infarcts were measured once and 3
      infarcts three times to the nearest 0.5 mm by each of two neurologists and two
      neuroradiologists using a ruler on hard-copy CT images. The longest diameter
      (designated AP), the greatest diameter at right angles to AP (designated LAT),
      and the number of slices showing the infarct were recorded and multiplied by the
      hard-copy minification factor to give IV dimensions. Volume (VOL) was calculated
      according to a previously published method. Interrater intraclass correlation
      coefficients for all infarcts combined were 0.98 (AP), 0.91 (LAT), and 0.97
      (VOL). Using all raters' measurements for any single infarct, the difference
      between the largest and the smallest measurement of AP and LAT was smallest (< 6
      mm IV) for Group A and largest (< 31 mm IV) for Group D. This difference was
      largest relative to the dimension being measured in Groups A and B, where it
      reached 101% of the mean of the four raters' measurements for the AP dimension
      being measured in Group B, and 70% of the dimension being measured in Group A.
      With all raters' measurements for any single infarct, the difference between the
      largest and smallest measurement of VOL was smallest (< 0.5 ml) for Group A and
      largest (< 260 ml) for Group D. This difference was largest relative to the mean
      volume of the infarct being measured in Group B, where it reached 153% of the
      mean of the four raters' measurements for VOL and reached 115% of the mean of the
      four raters' measurements for VOL in Group A. The authors conclude that infarcts
      can be measured on hard-copy images with good interrater agreement. When infarcts
      with a volume smaller than 5 ml are measured, differences between raters'
      measurements may exceed the size of the dimensions being measured.

PMID- 8555658
TI  - Coronary artery bypass grafting-associated ischemic stroke. A clinical and
      neuroradiological study.
AB  - Ischemic stroke occurring after coronary artery bypass grafting (CABG) has been
      attributed to various factors. Little is known about the perioperative course and
      radiological topography of CABG-associated strokes. In this study the clinical
      and computed tomography features of 25 patients with ischemic stroke following
      coronary artery bypass grafting were evaluated. Four patients awakened with focal
      signs, and 21 developed an ischemic stroke 1 to 22 days after surgery. All 4
      patients with early stroke had prolonged episodes of operative hypotension. Three
      of these patients had multiple subcortical and cortical infarcts. Of the 21
      patients with late-onset ischemic stroke, 19 had single-territory infarcts
      (middle cerebral artery territory, N = 12; posterior cerebral artery territory, N
      = 4; anterior cerebral artery territory, N = 3). Two patients had multiple
      territory infarcts in the anterior and posterior circulation. No watershed
      infarcts were found in any of the 25 patients. New-onset atrial fibrillation and
      location of ischemic stroke in a single vascular territory were more common in
      patients who had an ischemic stroke after an asymptomatic interval. Duplex
      sonographic findings of the carotid arteries and oculoplethysmography (OPG) were
      available for 13 patients. Only 1 patient had an ipsilateral carotid stenosis. Of
      21 patients who underwent postoperative two-dimensional echocardiography (with
      additional transesophageal echocardiography in 4), 2 had a left ventricular
      thrombus. These findings support the concept that post-CABG stroke is likely
      embolic.

PMID- 8555659
TI  - Usefulness of follow-up regional cerebral blood flow measurements by single
      photon emission computed tomography in the differential diagnosis of dementia.
AB  - The aim of this study was to evaluate whether follow-up measurements of regional
      cerebral blood flow (rCBF) by single-photon emission computed tomography (SPECT)
      provide additional information in the differential diagnosis of dementia. Thirty
      six patients (70 +/- 14 yr) with suspected dementia who had two technetium 99m
      hexamethylpropyleneamineoxime SPECT scans over 18 +/- 7 months were included in
      this retrospective study. The patients comprised three groups based on the final
      clinical diagnosis: (1) neurodegenerative disorder (NDD) including Alzheimer's
      disease (AD) (n = 13), frontotemporal lobe dementia (n = 2), progressive
      supranuclear palsy (n = 1), and mixed dementia (AD plus multiinfarct dementia
      [MID]) (n = 3); (2) MID (n = 8); and (3) psychiatric disorders (depression [n =
      7], psychosis [n = 1], and anxiety [n = 1]). Blinded to the clinical diagnosis
      and using visual analysis, the nuclear medicine physicians compared the second
      scan with the first scan for each patient to characterize temporal changes in
      rCBF. SPECT findings were categorized into three patterns of rCBF change:
      worsened, improved, and unchanged. Of the worsened rCBF group, 17 (85%) belonged
      to the NDD group whereas 2 (10%) and 1 (5%) belonged to the MID and psychiatric
      disorders groups, respectively. All 5 (100%) of the improved rCBF patients
      belonged to the psychiatric disorders group. Thus, worsening of rCBF favors the
      diagnosis of NDD whereas improvement in rCBF may mitigate against the diagnosis
      of NDD or MID. Follow-up rCBF measurements by SPECT thus provided additional
      information on the possible cause of dementia. A prospective study to further
      evaluate the usefulness of follow-up rCBF measurements by SPECT appears
      warranted.

PMID- 8555660
TI  - Time course of acetazolamide effect in normal persons.
AB  - The intravenous injection of the carbonic anhydrase inhibitor acetazolamide
      causes a sustained increase of blood flow velocity in the middle cerebral artery.
      This effect is used in the acetazolamide test of the so-called cerebrovascular
      reserve capacity. The acetazolamide test is performed routinely as a two-point
      measurement of the blood flow velocity by transcranial Doppler before and 15 to
      20 minutes after drug injection. Based on the assumption that evaluation of the
      time course will more sensitively detect an impaired cerebrovascular reserve
      capacity, suitable parameters for description of the time course were developed
      and normal values were established from 18 healthy persons (31 hemispheres). The
      mean value for the maximal increase of the mean flow velocity (MFV) was 29.7 +/-
      8.3 cm/sec (as percentage of increase, 62.0 +/- 17.3%) and the time of the
      maximal increase was 15.35 +/- 8.46 seconds. Also calculated were the velocity of
      the MFV rise to the maximal value (3.0 +/- 3.2 cm/sec/min), the mean of the
      changes of the continuously measured MFV to the baseline value (21.0 +/- 7.4
      cm/sec), and the integral of MFV represented by the plane under the MFV curve
      (967.8 +/- 350.0 cm). The best parameter for the description of the time
      dependency of the acetazolamide effect is the integral of MFV.

PMID- 8555661
TI  - Power Doppler ultrasound examination of the intracerebral and extracerebral
      vasculature.
AB  - Power Doppler is a new ultrasound technique based on the visualization of the
      Doppler power spectrum. In 22 patients with different lesions of brain-supplying
      vessels the results of power Doppler ultrasound were compared with those of
      digital subtraction angiography and conventional color Doppler ultrasound. In
      patients with intracranial high-degree stenoses, power Doppler was largely free
      of those artifacts that occur with conventional color Doppler (e.g.,
      echoshadowing and aliasing). The vessel lumen was seen in all patients with more
      than 80% stenoses. Power Doppler was superior to conventional color Doppler in
      visualizing both middle cerebral artery stenosis and intracerebral aneurysms.
      Power Doppler visualization of intracranial pathology was similar to
      visualization by digital subtraction angiography. Power Doppler appears to be a
      valuable tool in the noninvasive imaging of intracranial and extracranial
      pathological vascular conditions.

PMID- 8555662
TI  - Volumetric measurement of multifocal brain lesions. Implications for treatment
      trials of vascular dementia and multiple sclerosis.
AB  - This pilot study examined the reproducibility of serial magnetic resonance (MR)
      measurements of brain, ventricular, sulcal, and lesion volumes in patients with
      ischemic brain disease using an image analysis protocol designed at the
      University of Cincinnati. Five patients with a clinical history of brain ischemia
      had two separate MR brain imaging studies using the standard clinical MR imaging
      protocol at the University of Cincinnati Medical Center. The MR images on both
      film and tape were digitized and then analyzed according to the standardized
      image analysis protocol. Based on tape data, variability in volume measurements
      between the two MR studies, as measured by the coefficient of variation, ranged
      from 1% for intracranial volume to 8% for ventricular volume. Variability based
      on film data was slightly greater, ranging from 2% for intracranial volume to 12%
      for lesion volume. As part of a multicenter treatment trial of vascular dementia,
      this method was then used to analyze MR films in 13 patients with vascular
      dementia who all had an MR study at baseline and at 1 year. The mean annual
      change in lesion volume was 4 +/- 5 cm3 (a 24% increase from the baseline lesion
      volume); in ventricular volume, 7 +/- 8 cm3 (a 10% increase from baseline); and
      in sulcal volume, 13 +/- 25 cm3 (a 5% increase from baseline). This method of
      image analysis, using MR film or tape-generated data, can provide reproducible
      serial measurements of brain, ventricular, sulcal, and ischemic lesion volumes.
      This method, if applied in randomized treatment trials of vascular dementia or
      multiple sclerosis, can be used to monitor disease progression and to evaluate
      the effectiveness of a given therapy.

PMID- 8555663
TI  - Quantitative computed tomography and magnetic resonance imaging in aging and
      Alzheimer's disease. A review.
AB  - In recent aging research, quantitative techniques have been used to overcome
      limitations of qualitative interpretation of magnetic resonance and computed
      tomographic imaging. The purpose of this review is to summarize imaging results
      emphasizing quantitative studies using these two modalities in human aging.
      Magnetic resonance spectroscopy is viewed as an extension of imaging, and results
      of in vivo spectroscopic studies are included. Because Alzheimer's disease (AD)
      is closely related to aging, a discussion of quantitative imaging techniques that
      may distinguish normal elderly from patients with AD is included.

PMID- 8555664
TI  - Giant paraganglioma of the cauda equina in adolescence: magnetic resonance
      imaging demonstration.
AB  - A case of giant paraganglioma of the cauda equina is presented. This is only the
      second reported case in a minor and the first with magnetic resonance imaging. At
      13 cm long, this is the largest paraganglioma of the cauda equina ever recorded.

PMID- 8555665
TI  - Butterfly vertebra.
AB  - A 41-year-old man with low back pain and lumbar disc disease was found to have L
      3 butterfly vertebra on imaging studies as an incidental finding. This uncommon
      congenital anomaly of the vertebral column is usually asymptomatic and of no
      clinical significance. Awareness of this deformity and its imaging features is
      important diagnostically.

PMID- 8555666
TI  - Extracranial plasma cell granuloma presenting as a diffuse meningeal and
      intraparenchymal mass.
AB  - Plasma cell granuloma (PCG) is uncommon, characterized by polyclonal
      proliferation of mature plasma cells, usually within systemic organs. Only four
      previous cases have involved the central nervous system (CNS).

PMID- 8555667
TI  - Sarcoid myelopathy.
AB  - A 45-year-old woman with history of iritis, uveitis, and sarcoidosis of the skin
      presented with a subacute cervical myelopathy. Magnetic resonance imaging (MRI)
      showed patchy, multifocal, gadolinium-enhancing intramedullary lesions of the
      spinal cord, and extramedullary lesions of the basal cisterns and fourth
      ventricle. Symptoms and MRI abnormalities were improved within 1 month of
      corticosteroid therapy.

PMID- 8555668
TI  - Epidural hematoma producing Brown-Sequard syndrome: a case due to ruptured
      hemangioma with magnetic resonance imaging findings.
AB  - A man developed spontaneous spinal epidural hematoma secondary to ruptured
      hemangioma with a clinical picture resembling acute partial Brown-Sequard
      syndrome. Diagnosis by magnetic resonance imaging (MRI) allowed prompt surgical
      decompression and complete reversal of the neurological deficits. The diagnosis,
      etiology, and MRI findings of spinal epidural hematomas are discussed.

PMID- 8555669
TI  - Detection of intracranial internal carotid artery and middle cerebral artery
      vasospasm following subarachnoid hemorrhage.
AB  - Little is known about the accuracy of transcranial Doppler (TCD) sonography in
      detecting intracranial internal carotid artery (IICA) and middle cerebral artery
      (MCA) vasospasm. TCD was performed in 49 patients with subarachnoid hemorrhage to
      evaluate 90 IICAs and 87 MCAs during the vasospasm period. When a mean velocity
      of at least 90 cm/sec was used to indicate IICA vasospasm, there were 11
      positive, 42 negative, 4 false-positive, and 33 false-negative results.
      Sensitivity was 25% and specificity was 93%. When a mean velocity of at least 120
      cm/sec was used to indicate MCA vasospasm, there were 15 positive, 45 negative, 3
      false-positive, and 24 false-negative results (15 operator errors). Sensitivity
      was 38.5% and specificity was 93.7%. When the diagnostic criterion was changed to
      at least 130 cm/sec, specificities were 100% (IICA) and 96% (MCA) and positive
      predictive values were 100% (IICA) and 87% (MCA). The authors conclude that TCD
      accurately detects IICA and MCA vasospasm when flow velocities are at least 130
      cm/sec. However, its sensitivity may be underestimated and the importance of
      operator error, overestimated.

PMID- 8555670
TI  - Quantification of the urea herbicide, diuron, in water by enzyme immunoassay.

PMID- 8555671
TI  - Symptoms in forestry workers handling conifer plants treated with permethrin.

PMID- 8555672
TI  - Environmental impact of two molluscicides: niclosamide and metaldehyde in a rice
      paddy ecosystem.

PMID- 8555673
TI  - Transport of heavy metals and cations in a fly ash amended soil.

PMID- 8555674
TI  - Occurrence of butyltin residues in certain foodstuffs.

PMID- 8555675
TI  - Oxygen tolerance of fathead minnows previously exposed to copper.

PMID- 8555676
TI  - Effects of tributyltin and formaldehyde on the germination and growth of
      Phyllospora comosa (Labillardiere) C. Agardh (Phaeophyta: Fucales).

PMID- 8555677
TI  - Heavy metal concentrations of the endoparasitoid Glyptapanteles liparidis Bouche
      (Hymenoptera) in contaminated Lymantria dispar L. larvae (Lepidoptera).

PMID- 8555678
TI  - Biodegradation of the phenoxy herbicide MCPA by microbial consortia isolated from
      a rice field.

PMID- 8555679
TI  - Bioremediation of tannery effluent by aquatic macrophytes.

PMID- 8555680
TI  - Enhanced elimination of HgCl2 from natural water by a broad-spectrum Hg-resistant
      Bacillus pasteurii strain DR2 in presence of benzene.

PMID- 8555681
TI  - Dissipation of deltamethrin and fenvalerate residues in green gram (Vigna radiata
      (L.) Wilczek) under Indian climatic condition.

PMID- 8555682
TI  - Heavy metals in livers and kidneys of goats in Alabama.

PMID- 8555683
TI  - Changes in the levels of photosynthetic pigments in Phaseolus aureus Roxb.
      exposed to Hg and Cd at two stages of development: a comparative study.

PMID- 8555684
TI  - Heavy metal concentrations in the tissue of Sparus sarba Forskal, 1775 from the
      United Arab Emirates.

PMID- 8555685
TI  - Comparison of mercury accumulation among the brain, liver, kidney, and the brain
      regions of rats administered methylmercury in various phases of postnatal
      development.

PMID- 8555686
TI  - Plastic bags for stable storage of the water-soluble fraction of crude petroleum
      used in aquatic environment toxicity and tainting studies.

PMID- 8555687
TI  - Lindane transport in fresh water from wetlands of Brittany to the salt water of
      the Bay of Mont St. Michel (France).

PMID- 8555689
TI  - Toxicity of methyl tertiary butyl ether to Daphnia magna and Photobacterium
      phosphoreum.

PMID- 8555688
TI  - Influence of pre-, post-, and simultaneous perfusion of elevated calcium on the
      effect of ascending concentrations of lead on digoxin-induced cardiac arrest in
      isolated frog heart.

PMID- 8555690
TI  - Acute toxicity tests using Phyllospora comosa (Labillardiere) C. Agardh
      (Phaeophyta: Fucales) and Allorchestes compressa Dana (Crustacea: Amphipoda).

PMID- 8555691
TI  - Gammarus pulex (L.) feeding bioassay--effects of parasitism.

PMID- 8555692
TI  - Sporadic visceral neuropathy.
AB  - We encountered three cases of chronic functional colonic obstruction caused by
      intramural ganglion cell death. Morphologic and pharmacological studies were
      performed using resected specimens. The patients included a 59-year-old man, a 72
      year-old woman, and a 28-year-old man. Barium enema studies revealed segmental
      stenosis in their left colon. A mecholyl test was positive in all three cases and
      was useful in diagnosing this disorder. Histopathologic and cytometric
      examinations disclosed both degeneration and the disappearance of intramural
      ganglion cells. The number of muscarinic acetylcholine receptors was observed to
      increase in the muscle layers of the stenotic portion. In addition, the muscle of
      the affected region showed hypersensitivity to the muscarinic agonist
      (oxotremorine). These results seem to suggest that this disease is caused by a
      noncongenital injury to the intramural ganglion cells while the resulting
      stenosis is considered to reflect the degeneration of the ganglion cells. The
      etiology of ganglion cell death still remains to be clarified; however, we
      propose that patients with this disorder may represent a subset of patients with
      sporadic visceral neuropathy.

PMID- 8555693
TI  - Nitric oxide and active oxygen species in severe sepsis and surgically stressed
      patients.
AB  - To clarify how the kinetics of nitric oxide (NO) and active oxygen species are
      correlated with the occurrence of organ dysfunction in sepsis, the levels of
      monocyte-associated NO2, NO3, and active oxygen species were examined in severely
      septic patients with multiple organ dysfunction syndrome (group M; n = 5), and
      the results compared with those of postoperative patients who had undergone
      gastrointestinal surgery (group S; n = 5) and healthy volunteers (group C; n =
      10). The production of NO2 and NO3 by monocytes was significantly higher in group
      M than in the other two groups, while the production of active oxygen species by
      monocytes was significantly higher in groups M and S, than in group C. A
      significant correlation between the production of NO2 and that of active oxygen
      species by monocytes was noted only in group M. These findings indicate that the
      simultaneous activation of NO and active oxygen species production by monocytes
      is a prerequisite for the onset of multiple organ dysfunction in severe sepsis.

PMID- 8555694
TI  - Prognostic factors associated with differentiated thyroid cancer.
AB  - A multivariate analysis was conducted on the survival data of 180 patients who
      underwent curative resection for differentiated thyroid cancer between 1966 and
      1987, and the 10- and 20-year survival rates were found to be 80.6% and 73.1%,
      respectively. A survival analysis was also performed, testing the following
      factors: the patient's age at the time of diagnosis, tumor size, extraglandular
      extension, nodal status, distant metastases, operative procedure, sex, and
      histology. A univariate analysis found the initial six factors to be significant
      prognostic variables, but the latter two to be of no significance. On the other
      hand, the multivariate analysis showed that distant metastases, age, and tumor
      size were the most significant prognosticators. Thus, the age of the patient
      should be taken into consideration during the follow-up of treatment for
      differentiated thyroid cancer.

PMID- 8555695
TI  - Sutureless anastomosis using a biofragmentable anastomosis ring.
AB  - The biofragmentable anastomosis ring (BAR) is composed of polyglycolic acid and
      barium sulfate. When used for intestinal anastomosis, the BAR fragments after the
      anastomosis is established. We used this device in 43 patients. In three
      patients, the anastomosis with BAR was abandoned due to technical difficulties. A
      total of 43 anastomoses with BAR were performed in 40 patients. The operations in
      which BAR was used included right hemicolectomy in 12 patients, transverse
      colectomy in 7, sigmoidectomy in 11, small bowel resection in 5 and other bowel
      resections in 8. The time spent for the BAR anastomsis ranged from 7 to 30 min
      with a mean of 15.2 min, which was significantly shorter than that of
      conventional hand-sutured anastomosis in 23 cases. The fragmentation and
      excretion of the BAR occurred from 14 to 49 days later with a mean of 21.8 days.
      There was only one instance of anastomotic leakage (1/40, 2.5%), which occurred
      in a patient with a cytomegaloviral infection of the intestine. A postoperative
      barium enema study in 28 patients showed no passage disturbance through the
      anastomosis. In conclusion, the anastomosis using BAR is considered to be a
      simple, safe, and fast method for performing either colonic or small intestinal
      anastomosis.

PMID- 8555696
TI  - Clinical and experimental studies of the limulus test after digestive surgery.
AB  - A chromogenic limulus test (Toxicolor test) revealed a transiently increased
      blood endotoxin level in some patients after digestive surgery. However, most
      showed no clinical signs of endotoxemia. The Endospecy test of these specimens,
      which reacts specifically with endotoxin, did not show a high value, while the
      Gluspecy test, which reacts specifically with (1-->3)-beta-D-glucan (glucan),
      did. These findings thus suggested that the gauze used for surgery contains a
      large amount of glucan. The intraperitoneal injection of this gauze-saline into
      rats results in a phenomenon similar to that observed in clinical studies. These
      findings suggested the involvement of substances other than endotoxin such as
      glucan in the postoperative positive-Toxicolor phenomenon. In addition, the
      Toxicolor test also showed a higher value in patients with liver cirrhosis than
      in those without. In an experimental study in rats, the liver cirrhosis group
      also showed a significantly high value. These results therefore suggest that the
      glucan clearance mechanism is impaired in the reticuloendothelial system in liver
      damage such as cirrhosis.

PMID- 8555697
TI  - Prevention of local recurrence by extended lymphadenectomy for rectal cancer.
AB  - This study was undertaken to determine if the degree of lymphadenectomy
      correlates with the prevention of local recurrence. The authors retrospectively
      reviewed the clinical data of 269 patients who underwent curative surgery for
      rectal cancer. The study was divided into three periods based on the method of
      lymphadenectomy as follows: period I (1963-1979) when extended lymphadenectomy
      was not performed; period II (1980-1985) when this was partially done with no
      attempt to dissect the obturator and proximal middle rectal lymph nodes; and
      period III (1986-1990) when this was completely performed for patients with
      appropriate indications. The local recurrence rates were 21%, 10%, and 8% for
      Periods I, II, and III, respectively (P < 0.05). The incidence of local
      recurrence tended to be greater in period I versus periods II and III according
      to type of operation, location, and stage of the primary tumors. The local
      recurrence rates arising from lateral node metastases were 11%, 4%, and 2% for
      periods I, II, and III, respectively (P < 0.05), while the incidence related to
      an insufficient surgical margin was approximately 5% throughout the three
      periods. We thus conclude that the degree of lymphadenectomy is a major
      determinant of local recurrence following a curative operation for rectal cancer.

PMID- 8555698
TI  - Esophageal transection using a biofragmentable anastomosis ring in dogs.
AB  - Since the first publication on the new anastomosis technique using a
      biofragmentable anastomosis ring (BAR) by Hardy in 1985, various studies have
      been performed to investigate the superiority of this type of anastomosis, and it
      has since been reported that the BAR was safely used not only in large and small
      bowel anastomosis, but in cholecystojejunal and gastrojejunal anastomosis as
      well. In this study, the feasibility of the BAR for esophageal transection was
      investigated. Seven dogs were operated on, and one died of intraabdominal
      bleeding on the operative day while another died of leakage at the site of
      gastrotomy on the 3rd postoperative day. These deaths were all considered to be
      due to simple technical errors not directly related to the use of the BAR. The
      postoperative recovery of the other five dogs was uneventful, and the ring
      eventually disintegrated into several small fragments that passed out of the body
      in the faces between the 14th and 21st postoperative days. The dogs were killed
      on the 28th postoperative day, and both gross and histological examinations,
      revealed that the transection had been successful. Neither leakage nor
      significant stenosis at the site of transection was found. Our results suggested
      that the BAR could be used for esophageal transection and is thus recommended as
      an easy-to-learn, time-saving, and safe technique for esophageal operations.

PMID- 8555699
TI  - Experimental tracheal replacement using the esophagus and an expandable metallic
      stent.
AB  - An experimental study was conducted to investigate whether a segment of
      autogenous esophagus with its lumen supported by an expandable metallic stent
      (EMS) could be successfully used as a tracheal substitute. Seven rings of the
      cervical trachea were circumferentially removed and reconstructed by interposing
      a pedicled segment of the esophagus with an EMS in six mongrel dogs. The
      interposed esophagus was observed endoscopically at various stages after the
      operation. By 1 month, the EMS was found to be buried under the esophageal
      mucosa, and the lumen was patent. The dogs died 5, 17, 61, 92, 210, and 478 days
      after the operation, but the cause of death could not be determined by postmortem
      examination and no respiratory tract complications were detected. The results of
      this study indicated that a segment of the esophagus with its lumen supported by
      an EMS could work as a reliable tracheal substitute, though its practical use is
      not clinically feasible. Nevertheless, we conclude that some autogenous material
      other than the esophagus with its lumen supported by an EMS could provide a
      feasible method for tracheal replacement.

PMID- 8555700
TI  - Use of a pericardial fat pad flap for preventing bronchopleural fistula: an
      experimental study focusing on the angiogenesis and cytokine production of the
      fat pad.
AB  - An experimental study was conducted to determine whether pericardial fat tissue
      could induce neovascularization and produce cytokines related to tissue repair.
      Neovascularization was examined using chick chorioallantoic membranes. Pieces of
      pericardial fat tissue, omentum, and intercostal muscle were individually placed
      on a number of chorioallantoic membranes and neovascularization induced by each
      material was assayed 6 days after the implantation. The intensity of
      neovascularization was in the order of pericardial fat > or = omentum > muscle.
      Cytokines, such as interleukin 1 (IL-1) alpha and beta, tumor necrosis factor
      alpha (TNF alpha), interferon-gamma (IFN-gamma), and interleukin 6 (IL-6) were
      assayed in a culture supernatant of pericardial fat tissue. The latter was
      obtained 24 h after the addition of lipopolysaccharide (LPS) following various
      incubation times. All cytokines other than IFN gamma are known to play a part in
      tissue repair, whereas IFN gamma is negatively related to tissue repair because
      it inhibits fibroblast growth. The pericardial fat tissue incubated with LPS
      produced a certain amount of IL-1 on day 1, and TNF alpha on days 1 and 8,
      whereafter these values decreased to an undetectable level. Irrespective of the
      addition of LPS, a large amount of IL-6 was observed in the supernatant of
      pericardial fat tissue and it was detectable until day 29. On the contrary, INF
      gamma was not detected at any assay time. These observations suggest that a
      pericardial fat pad flap could possibly be beneficial in the prevention of
      bronchopleural fistula after pulmonary resection.

PMID- 8555701
TI  - The liver regenerative response elicited by antisecretory agents in partially
      hepatectomized rats: a comparison between omeprazole and famotidine.
AB  - Liver regeneration after omeprazole (OMP) or famotidine (FAM) administration was
      examined in 66% hepatectomized rats. The regeneration was evaluated by the liver
      weight as a percentage of body weight (LRR) and the proportion of hepatocytes in
      mitosis per 1,000 counts (MI). Administration of OMP 0.4 mg/kg per day for 3 or 7
      days suppressed LRR and MI 3 and 7 days after hepatectomy. However, the
      administration of FAM 0.8 mg/kg per day for 3 or 7 days did not change either LRR
      or MI. Increased gastrin levels in the blood were seen only after OMP
      administration. The food intake was unchanged by OMP or FAM, but FAM increased
      water intake. The liver functional score, glutamic pyruvic transaminase and
      alkaline phosphatase in the blood all increased with OMP, but FAM had no apparent
      effect on the hepatic or renal function. These observations suggest that a large
      dosage of OMP suppresses liver regeneration, while FAM appears to have no
      meaningful effect on regeneration.

PMID- 8555702
TI  - Familial non-multiple endocrine neoplasia medullary thyroid carcinoma: report of
      a case confirming a new clinical entity in Japan.
AB  - Most hereditary medullary thyroid carcinomas (MTC) occur in association with
      multiple endocrine neoplasia (MEN) type 2 syndromes. Since Farndon et al.
      reported two kindreds, that is collections of relatives, with familial non-MEN
      MTC in 1986, only five kindreds with this disorder have been reported in the
      English literature. In this paper, we describe a rare Japanese kindred with
      familial non-MEN MTC, confirming the existence of this distinct clinical entity
      in Japan. A 42-year-old woman underwent a left hemithyroidectomy with modified
      neck dissection (MND) under a diagnosis of sporadic MTC at 28 years of age. She
      developed lymph node metastasis in the right neck region 7 years after the
      initial surgery, and underwent MND and right hemithyroidectomy. Although no
      findings of MTC were histologically confirmed in the resected right thyroid lobe,
      C-cell hyperplasia was observed. Hereditary MTC was strongly suspected, but we
      could not confirm specific manifestations associated with MEN type 2 in any
      family members. However, 7 years later, a paternal aunt and cousin were diagnosed
      with MTC. Other family members were evaluated by ultrasonography and calcium
      pentagastrin provocation testing, and three additional patients with MTC across
      two generations were found. None of these patients had any extrathyroidal
      manifestations associated with MEN type 2, and the entity of familial non-MEN MTC
      was confirmed.

PMID- 8555703
TI  - Postoperative chylothorax following partial resection of mediastinal
      lymphangioma: report of a case.
AB  - We report herein the rare case of a 20-year-old man in whom a mediastinal
      lymphangioma was incidentally detected by a chest roentgenogram taken during a
      routine health examination. Both computed tomography and magnetic resonance
      imaging confirmed a mass measuring 3 x 7 cm in diameter in the left anterior
      mediastinum. A thoracoscopic exploration was done, which confirmed a diagnosis of
      mediastinal lymphangioma, and 3 days later a sternotomy was performed. However,
      the tumor could not be completely extirpated due to partial invasion. Following
      the thoracoscopic procedure, a chylous discharge developed which was difficult to
      treat conservatively and he continued to drain 700-1,000 ml of chyle daily 2
      weeks following the tumor extirpation. Therefore, a right thoracotomy with
      ligation of the thoracic duct was performed which resolved the chylothorax. The
      patient remains well without any regrowth of the regional tumor 9 months after
      his operation.

PMID- 8555704
TI  - Primary small cell carcinoma of the esophagus: report of a case.
AB  - A case of esophageal small cell carcinoma successfully treated with combination
      therapy consisting of both pre- and postoperative chemotherapy as well as
      surgical resection is presented. A 74-year-old man presented with a small cell
      carcinoma measuring 11 cm in diameter in the lower half of his thoracic
      esophagus. After undergoing preoperative chemotherapy with cisplatin (25 mg, iv,
      days 1 through 5), the gross tumor completely regressed. However, a microscopic
      focus of residual cancer showing squamous cell carcinoma was found in the
      resected esophageal specimen. The patient received an additional two courses of
      postoperative chemotherapy with cisplatin (75 mg, iv monthly). He has since
      survived more than 9 years with no evidence of recurrent disease. We herein
      report a rare case of a patient with esophageal small cell carcinoma who
      demonstrated a complete cure.

PMID- 8555705
TI  - Appendiceal intussusception due to an appendiceal malignant polyp--an association
      in a patient with Peutz-Jeghers syndrome: report of a case.
AB  - A 40-year-old woman with Peutz-Jeghers syndrome and an appendiceal
      intussusception is reported. In this patient, the lead point was a large sessile,
      appendiceal polyp. The invaginated and inverted portion of the appendix resembled
      the long stalk of a pedunculated polyp on roentgenography and endoscopic
      examination. Histologically, the appendiceal polyp was a villous adenoma with
      mild to severe atypia and focal carcinoma in situ. In patients with Peutz-Jeghers
      syndrome, hamartomatous polyps and colorectal adenomatous polyps with highly
      malignant potential can coexist and must be managed appropriately. Therefore,
      when evaluating a polypoid or a pedunculated lesion in the cecal lumen, the
      possibility of an appendiceal intussusception should also be investigated.

PMID- 8555706
TI  - Hepatocellular carcinoma associated with lupoid hepatitis: a review of Japanese
      reports.
AB  - A 66-year-old woman was diagnosed as having lupoid hepatitis due to the presence
      of hypergammaglobulinemia, lupus erythematosus cells, and positivity for
      antinuclear, anti-DNA, and anti-smooth muscle antibodies. None of the serum
      hepatitis B markers were positive. Symptomatic relief was obtained by
      prednisolone administration. Five years after the diagnosis of lupoid hepatitis,
      hepatocellular carcinoma (HCC) was detected by ultrasonography and computed
      tomography, after which hepatectomy was performed. Although transcatheter
      arterial embolization was done on two occasions and repeat hepatectomy was
      performed twice for recurrent HCC, her liver function remained good with the
      prednisolone treatment. Antibody for hepatitis C virus has been negative since
      our first check in 1992. As of this writing, the patient has been alive and well
      6 years and 2 months after the first hepatectomy. There have been no previous
      reports of 6-year survival after hepatectomy for HCC associated with lupoid
      hepatitis.

PMID- 8555707
TI  - Mucoepidermoid carcinoma of the pancreas: report of a case.
AB  - We present herein the case of a 64-year-old man diagnosed as having a
      mucoepidermoid carcinoma of the pancreas. The tumor originated in the tail of the
      pancreas and invaded the spleen, left adrenal gland, left kidney, and transverse
      colon. Liver and peritoneal metastases were also noted. Despite surgical
      treatment and adjuvant chemotherapy, the disease progressed rapidly and the
      patient died of cachexia 4 months after his initial diagnosis. Mucoepidermoid
      carcinoma of the pancreas is a rare entity, and is believed to be a form of
      adenosquamous carcinoma known as adenoacanthoma. However, in this patient, no
      differentiated squamous cell component could be detected. In fact, the tumor was
      composed of mucin-producing cells, epidermoid cells, and intermediate cells.
      Immunohistochemical staining for the carcinoembryonic antigen, CA19-9, and SPan-1
      demonstrated a production of cancerous mucin in the epidermoid cells, suggesting
      that mucoepidermoid carcinoma may arise from the squamoid metaplasia of an
      adenocarcinoma.

PMID- 8555708
TI  - Multiple endocrine neoplasia type 1 presenting as insulinoma, gastrinoma, and
      postbulbar duodenal ulcers: report of a case.
AB  - We report herein the unusual case of a 55-year-old man with multiple endocrine
      neoplasia type 1 presenting as hyperparathyroidism, hyperpituitarism, insulinoma,
      and gastrinoma with postbulbar duodenal ulcers. The patient was referred to our
      hospital for further investigations of nephrolithiasis, acromegaly, and
      hematemesis. Laboratory studies showed high serum levels of calcium, parathyroid
      hormone, growth hormone, insulin, gastrin, and prolactin. Computed tomography of
      the cranial cavity demonstrated an enlargement of the serra turcica and swelling
      of two parathyroid glands in the neck. Computed tomography and angiography of the
      abdomen also showed a mass in the head of the pancreas. Endoscopy demonstrated
      reflux esophagitis, erosive gastritis, and multiple postbulbar duodenal ulcers.
      We diagnosed this patient as having multiple endocrine neoplasia type 1, with
      concomitant lesions of the pituitary gland, parathyroid glands, and islet cells
      of the pancreas. Following excision of the two enlarged parathyroid glands, his
      serum calcium and parathyroid hormone levels fell to within the normal range.
      Thereafter, a total gastrectomy was performed to alleviate the frequent bleeding
      from the upper gastrointestinal tract. However, resection of the pancreatic mass
      could not be performed owing to severe inflammation around the duodenum, probably
      induced by the postbulbar duodenal ulcers.

PMID- 8555709
TI  - Ruptured bronchial artery aneurysm associated with pleural telangiectasis and
      tortuous portal obstruction: report of a case.
AB  - A 25-year-old woman presenting with an emergent condition of massive hemothorax
      due to a ruptured bronchial artery aneurysm was successfully treated by
      transcatheter arterial embolization. She had previously undergone portosystemic
      shunt splenopneumopexy for hepatic portal hypertension at 6 years of age. When
      undergoing right thoracotomy for the removal of a clot, a prominent
      telangiectasis on the pleural surface was noted. The lesion appeared to be a rare
      systemic vascular abnormality although this could not be confirmed.

PMID- 8555710
TI  - Surgical treatment of an enormous aneurysmal portahepatic venous fistula: report
      of a case.
AB  - We report herein the case of a 20-year-old woman in whom an enormous aneurysmal
      portahepatic venous fistula was found. The portal aneurysm developed in the
      anterior inferior segment of the right hepatic lobe, and communicated with the
      right portal vein and the right hepatic vein. Due to the enormous size of the
      shunt, and because the patient's venous blood ammonia level increased by about
      twofold after eating, a right lobectomy of the liver was performed. A review of
      the available literature and a discussion of the most appropriate treatment
      follows the presentation of this case.

PMID- 8555711
TI  - DSM-III-R and persons with dual diagnoses: conceptual issues and strategies for
      future research.
AB  - Diagnosis of mental health needs in people with mental retardation using the DSM
      III-R manual was critically reviewed. Conceptual issues included the interaction
      of different diagnosis categories; the cognitive and linguistic competencies
      often required for diagnosis; the potential mismatch between psychopathology in
      people with mental retardation and the DSM-III-R nosology; and issues relating to
      multi-axial classification. Strategies identified to explore and resolve these
      issues include better documentation of the frequency and nature of these problems
      when using unmodified DSM-III-R criteria, better empirical piloting of modified
      diagnostic criteria with people with severe and profound mental retardation, and
      the use of social validity data to identify potential mismatches between
      psychopathology in people with mental retardation and DSM-III-R diagnoses.

PMID- 8555712
TI  - Neuropsychological effects of subsequent exposure to phenylalanine in adolescents
      and young adults with early-treated phenylketonuria.
AB  - Severe mental handicap in phenylketonuria (PKU) can be prevented if dietary
      treatment is implemented at birth. Controversy remains about the optimum age for
      terminating treatment. A group of adolescents and young adults with PKU from the
      West of Scotland Register was identified which had received early treatment, been
      well-controlled on diet, ceased treatment at 10 years old and subsequently were
      hyperphenylalaninaemic for 3 years or more. They were given a battery of
      neuropsychological tests and their results were compared with those of on-diet
      subjects with PKU and normal controls. The findings generally supported the view
      that dietary cessation at age 10 is sufficient to prevent a substantial reduction
      of cognitive and motor ability, and that the central nervous system is probably
      mature enough to withstand the toxic effects of high blood phenylalanine by then.
      However, there were minor indications, in keeping with Welsh et al.'s hypothesis
      [M.C. Welsh, B.F. Pennington, S. Ozonoff, B. Rouse & E.R.B. McCabe (1990)
      Neuropsychology of early-treated phenylketonuria: specific executive function
      deficits.

PMID- 8555713
TI  - Characteristics of the eating disorder in Prader-Willi syndrome: implications for
      treatment.
AB  - Over-eating and resultant obesity is well recognized as a central feature of the
      Prader-Willi Syndrome (PWS). The eating behaviour of 13 subjects with PWS was
      been studied retrospectively over a 28-day period and also by direct observation
      when given free access to food. Changing cognitions normally associated with food
      intake (e.g. changes in hunger) were assessed using visual analogue scales (VAS)
      and by asking subjects to rate photographs of particular foods. Eight out of 13
      subjects (61%) with PWS had to have their access to food severely restricted. Ten
      (77%) ate excessive amounts when given free access to food, and although feelings
      of 'hunger', 'desire to eat' and 'fullness' changed in the expected direction,
      these changes were delayed, compared to a control group, and only occurred after
      eating a significantly greater amount of food. Ratings of 'hunger' and 'fullness'
      started to return to pre-meal levels sooner than in the controls. The present
      authors consider that PWS is an example of genetic obesity secondary to an
      impaired satiety response. These observations have important implications for
      treatment.

PMID- 8555714
TI  - Sexual abuse of adults with learning disabilities.
AB  - This paper reports a clinical study of reported or disclosed sexual abuse of
      adults with learning disabilities. The findings support the results of a recent
      survey [V. Turk & H. Brown (1993) Sexual abuse of adults with learning
      disabilities: results of a two-year incidence survey. Mental Handicap Research 6,
      193-216] but some differences were found, particularly with regard to sex of the
      survivors. The study also illustrates more than previous studies a link between
      sexual abuse and sexualized and inappropriate sexual behaviour and other
      challenging behaviours in men with learning disabilities.

PMID- 8555715
TI  - The form and function of challenging behaviours.
AB  - Aspects of the topography and behavioural function underlying the challenging
      behaviours of all people with learning disabilities and challenging behaviour (n
      = 70) in a defined geographical area were investigated. Results indicated that:
      (1) more severe challenging behaviours were shown by people with more severe
      disabilities; (2) a significant minority (44%) of people showed more than one
      form of challenging behaviour, this rising to 79% among people with more severe
      challenging behaviours; and (3) cross-sectional analyses revealed specific
      clusters of problematic, aggressive and self-injurious behaviours. Analysis of
      information derived from the Motivation Assessment Scale (MAS) indicated that (5)
      the most common functions of challenging behaviours appeared to be 'self
      stimulation' (for self-injury, destructiveness and 'other' challenging
      behaviours) and securing the attention of carers (for aggressive behaviours).
      However, (6) parametric analyses failed to identify any consistent relationships
      between the form and function of an individual's challenging behaviour for
      aggressive, destructiveness and 'other' challenging behaviours, but (7) clients
      with self-injurious behaviour were significantly more likely to score highly on
      the 'self-stimulation' sub-scale than other sub-scales of the MAS. Finally, (8)
      significant consistency of behavioural functions across different forms of
      challenging behaviours shown by the same individual were found for the two
      combinations of aggressive-destructive behaviours and self-injury-'other'
      behaviours.

PMID- 8555716
TI  - Ageing in adults with Down's syndrome in institutionally based and community
      based residences.
AB  - Seventy-one subjects with Down's syndrome (DS), between the ages of 29 and 68
      years, and 46 matched controls (without DS) were examined for intelligence,
      memory (short- and long-term memory, and spatial and temporal orientation),
      communication (receptive, expressive and written language) and daily living
      skills (personal, domestic and community daily living skills). All subjects were
      screened on hearing and visual functions, thyroid functions, depression and
      dementia. DS-subjects and controls were matched on chronological age, mental age,
      living conditions and male/female ratio. Comparisons were made between five
      subgroups (1) non-demented institutionalized subjects with DS (DSi-group; n =
      35); (2) non-demented institutionalized controls without DS (Ci-group; n = 22);
      (3) demented institutionalized subjects with DS (n = 10); (4) non-demented
      subjects with DS living in group homes (DSg; n = 26); and (5) non-demented
      controls without DS living in group homes (Cg; n = 24). Institutionalized and non
      institutionalized subjects, as well as demented and non-demented subjects
      differed significantly on all functions measured. Multiple regression analysis
      was performed to examine the influence of age and sensory deficits on adaptive
      and cognitive functioning. In DSg subjects, significant associations were found
      between age and mental age, and between age and performances on written language.
      In (non-demented) DSi subjects, significant relations were found between age and
      memory functions observed in daily circumstances. Moreover, in the (non-demented)
      DSi elderly, visual impairment was significantly related to depressed performance
      on daily living skills. No age effects were seen in control subjects. Infirmities
      of old age like dementia and sensory deficits were far more common in people with
      DS than in controls. Psychiatric and diagnostic aspects of clinical depression
      and dementia were emphasized in particular.

PMID- 8555717
TI  - Cross-national comparisons of ageing mothers of adults with intellectual
      disabilities.
AB  - Ageing (55+ years) mothers of adults with intellectual disabilities in the
      Republic of Ireland, Northern Ireland and the United States were compared with
      respect to three general issues. Firstly, to what extent do the adults in these
      three countries differ in their level of reliance on their mothers? Secondly, do
      the mothers differ in the extent to which they have made plans for the future
      care of their son or daughter with intellectual disabilities? Thirdly, do the
      mothers differ in physical, social and psychological well-being? These cross
      national comparisons were undertaken to examine the extent to which lifelong
      caregiving has either a common influence on mothers across national boundaries,
      or, alternatively, whether the cultural context exerts a unique influence on
      mothers in each country. Findings supported the latter explanation, even when
      background characteristics were statistically controlled.

PMID- 8555718
TI  - Two longitudinal studies of the abilities of people with Down's syndrome.
AB  - A cohort of subjects with Down's syndrome born in South Wales, UK, in 1964, 1965
      and 1966, and living at home, was studied as infants, teenagers and young adults
      (the original cohort). Carers were interviewed and the abilities of the subjects
      assessed, using a variety of measures. Average scores of the cohort improved over
      the years, although the rate of progress slowed down between the teenage and
      adult years. Scores were related to social class, stimulation given in the home,
      and at older ages, maternal age at the birth of the subject. This latter finding
      was unexpected. A comparative cohort of subjects with Down's syndrome from South
      Wales born in 1973, 1974 and 1975 was studied as infants and teenagers. They were
      at the same stage as the original cohort as infants and teenagers, but living 9
      years later. In spite of the comparative cohort coming from a favoured
      background, in terms of social class and having access to improved services, mean
      scores at the teenage stage were only significantly better on one test of
      language than those of the original cohort at the same age. Most studies find
      that females with Down's syndrome have higher abilities than males: this was the
      case for the original cohort, but not for the comparative cohort.

PMID- 8555719
TI  - Behavioural disturbance in people with Down's syndrome and dementia.
AB  - Behavioural disturbance associated with dementia in people with Down's syndrome
      has not been fully researched. This study investigated such problems in demented
      Down's syndrome subjects and nondemented Down's syndrome controls. Changes in
      mood, difficulty with communication, gait deterioration, loss of self-care
      skills, sleep disturbance, day-time wandering and urinary incontinence were found
      to be associated with dementia. Problems giving the greatest cause for concern to
      carers were restlessness, loss of communication skills, urinary incontinence and
      wandering. Care provision specifically focused on management of behavioural
      disturbance in individuals who develop dementia is recommended.

PMID- 8555720
TI  - Overweight and obesity amongst Down's syndrome adults.
AB  - Two hundred and one individuals with Down's syndrome were assessed for evidence
      of overweight and obesity. Thirty-one per cent of males and 22% of females were
      overweight, while 48% males and 47% females were obese. Overweight and obesity
      was significantly associated with living in the family home compared to
      supervised community units or in hospital. No association with the degree of
      learning disability was found.

PMID- 8555721
TI  - Mortality in a hospitalized mentally handicapped population: a 10-year survey.
AB  - The mortality experiences of a hospitalized mentally handicapped population
      between 1981 and 1990 (inclusive) were examined. A continued trend for increasing
      longevity in both males and females was found, with mean ages at death now
      approaching those in the general population. The commonest cause of death was non
      tubercular respiratory infection, from which patients were particularly at risk
      during the months of December to February (inclusive). Patients diagnosed as
      suffering from psychoses other than schizophrenia and mood disorder had an
      increased mortality and should be thoroughly investigated for the presence of
      organic pathology. Epilepsy and Down's syndrome were associated with increased
      risk of earlier death, although in the case of Down's syndrome there has been a
      marked increase in longevity.

PMID- 8555722
TI  - A lethal case of atlantoaxial dislocation in a 56-year-old woman with Down's
      syndrome.
AB  - A case of fatal atlantoaxial dislocation is reported in a 56-year-old woman with
      Down's syndrome. The literature indicates such a case to be a rarity; however,
      this may be a result of the predominance of younger age samples. The implications
      of this are discussed.

PMID- 8555723
TI  - Histrionic personality disorder as pseudo-learning disability.
AB  - The case of a 20-year-old woman with a histrionic personality disorder is
      described. She claims to have a mild learning disability, and indeed, is
      receiving special college education for people with learning disabilities and has
      a specialist learning disability social worker, despite being of above average
      intelligence. Aetiologically, her persona is viewed as a psychological defence,
      rather than a deliberate attempt at deception. A process of
      'institutionalization' appears to have occurred and compounded the problems with
      further regression. Psychiatrists and professionals in allied disciplines should
      not accept that a person has a learning disability purely because that person
      tells you that he or she has one.

PMID- 8555724
TI  - Transvestism in a person with learning disabilities presenting with behavioural
      problems.
AB  - A case of transvestism is reported in a 47-year-old man with learning
      disabilities. He had developed encephalitis in childhood, which had resulted in
      moderate learning disabilities and epilepsy, and had been living in institutions
      from the age of six. He did not have any chance to express his sexual desire and
      this frustration manifested as aggressive behaviour. Recently, he moved to a
      community home and his deviant sexual behaviour became apparent. Management of
      his problems involves organizing a behavioural programme linking his cross
      dressing with aggressive behaviour.

PMID- 8555725
TI  - Catatonic syndrome following recovery from neuroleptic malignant syndrome.
AB  - In June 1992, a 51-year-old Caucasian man with a mild learning disability was
      prescribed chlorpromazine and thioridazine for sleeplessness and agitation. He
      developed neuroleptic malignant syndrome (NMS) which was treated successfully
      with intravenous diazepam. Without further exposure to neuroleptics, the patient
      became acutely unwell with signs of catatonic syndrome in March 1993 and
      responded to oral diazepam. When the dose of diazepam was reduced in August 1993,
      the catatonic syndrome recurred and responded to an increase in his oral
      diazepam. In the past, the patient had been admitted to hospital in 1983 and 1986
      with severe extrapyramidal symptoms and parkinsonism following prescription of
      neuroleptics for agitation. This case provides evidence that patients with a
      predisposition to catatonic syndrome may be at increased risk of developing NMS,
      and therefore, should not be treated with neuroleptics.

PMID- 8555726
TI  - Familial choroid plexus calcification and mental retardation.

PMID- 8555727
TI  - 5-hydroxytryptamine: considerations about discovery, receptor classification and
      relevance to medical research.
AB  - Serotonin (5-hydroxytryptamine; 5-HT), an endogenous and ubiquitous monoamine,
      has become a subject of "explosive" research. Though its vasoconstrictor
      properties were first noticed in defibrinated or clotted blood, 5-HT was
      discovered 75 years later going through several denominations such as
      "enteramine, serotonin or 5-HT". Once confirmed that serotonin, enteramine and 5
      HT were the same substance, the compound was synthesized and efforts with a view
      to analyze 5-HT receptors were performed. On the basis of the actions of 5-HT and
      other drugs on several smooth muscle experimental preparations, it was originally
      suggested that 5-HT could act via different receptors. Thus, Gaddum and Picarelli
      proposed the "D" and "M" classification based on the differential sensitivity of
      guinea pig ileum 5-HT-induced contraction to some drugs. Later on, this
      classification was confronted with the new Peroutka's 5-HT, and 5-HT2
      classification derived from radioligand binding studies. Since these 5-HT
      receptors were being referred to by many names, an international committee
      formulated some criteria for the characterization and a framework for the
      nomenclature of 5-HT receptors into 5-HT1, 5-HT2 and 5-HT3 categories. More
      recently, functional evidence unrelated to activation of the above 5-HT receptor
      types was given and a new 5-HT (5-HT4) receptor was proposed to exist. From this
      stage, molecular biologists have been cloning several 5-HT receptors which are
      different from the various receptors (sub)types characterized thus far. This
      review is focused on the discovery of 5-HT and the evolution of the
      classification of 5-HT receptors, from historical remarks to the modern concepts
      about receptor characterization; furthermore, the relevance of this development
      to medical research is considered.

PMID- 8555728
TI  - Ovine lentivirus infection: an animal model for pediatric HIV infection?
AB  - While the incidence of the human immunodeficiency virus (HIV) infection has
      leveled off somewhat in homosexual men, infection in women, children and
      adolescents is rising. Unless effective preventive measures are introduced, the
      number of pediatric patients with HIV and related illnesses will continue to
      increase. Animal models play a key role in the understanding of the pathogenesis
      and in the establishment of therapeutic approaches of infectious diseases. Ovine
      lentivirus (OvLV) comprises a subgenus of the lentivirus genus in the family
      Retroviridae, that shares genotypic, phenotypic and pathogenic features with HIV.
      Infection of sheep with OvLV results in a progressive chronic disease
      characterized by cachexia and chronic active inflammation in the lungs, lymph
      nodes, joints, mammary gland and the central nervous system. Pulmonary lesions in
      OvLV-affected sheep consist of lymphoid interstitial pneumonia (LIP) and
      lyphocytic alveolitis. Similarly, these pulmonary lesions also occur in up to 40%
      of HIV-infected children and in some adults with AIDS. Neonatal lambs
      experimentally inoculated intratracheally with OvLV develop LIP in 5 to 6 months,
      thus shortening by several years the natural incubation period and resembling the
      shorter incubation period observed in children with HIV-associated LIP. However,
      unlike HIV, OvLV does not infect CD4+T lymphocytes; OvLV only infects and
      replicates in macrophages. Recent studies indicate that macrophage tropic HIV
      plays an important role in disease progression. Similarities between HIV and OvLV
      argue for the use of ovine lentivirus infection as a model to advance in the
      understanding of some of the aspects of HIV infection.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8555729
TI  - Salmonella typhimurium infection in mice: lymphoproliferative responses to
      fractionated protein antigens.
AB  - The proliferative response of spleen cells of mice immunized with S. typhimurium
      by the oral route was analyzed using antigen fractions from a protein extract of
      the bacteria. Mice that survived the challenge with a virulent strain of
      Salmonella and normal mice were also studied. Mice were immunized with three
      doses of live S. typhimurium on consecutive days (3C) or once a week for 3 weeks
      (3W). Fractions 12-100 kDa from the protein extract were separated by SDS
      polyacrylamide gel electrophoresis, electroblotted to nitrocellulose membranes
      and processed to obtain particulate antigens for use in lymphocyte cultures. Mice
      immunized weekly showed a higher survival rate and responded to more antigenic
      fractions. We identified three fractions of 68-76, 50-52, and 42-45 kDa that were
      immunodominant for spleen cells from S. typhimurium immunized mice and from
      survivors to the challenge with the virulent strain.

PMID- 8555730
TI  - Characterization of cDNAs encoding adhesin proteins involved in trichomonas
      vaginalis cytoadherence.
AB  - Trichomonas vaginalis cytoadherence is mediated by four adhesins (AP65, AP51,
      AP33 and AP23). Adhesin gene expression was previously shown to be up-regulated
      by iron. Therefore, a cDNA library was constructed from mRNA of T. vaginalis
      grown in a high-iron medium. Ten cDNA clones (three for AP65, one for AP51, and
      six for AP33) were recognized with polyclonal antiserum or monoclonal antibody
      raised against these adhesins. No cross-hybridization among cDNAs of the three
      adhesins was observed in Southern analysis, confirming restriction mapping
      analysis of representative cDNAs. Southern analysis probed with representative
      cDNAs of the adhesins indicated multiple copies for each of the three adhesin
      genes. Northern analysis showed transcripts of 1.8 kilobases (kb), 1.4 kb, and
      0.9 kb for AP65, AP51 and AP33, respectively. Consistent with adhesin expression,
      mRNAs for these adhesins were detected only when parasites were grown in high
      iron conditions. Specific antibodies eluted from E. coli expressing recombinant
      proteins reacted only with the respective parasite adhesins. Recombinant proteins
      bind to fixed HeLa cells and competed with radiolabeled trichomonad adhesins for
      binding. Although proteinase activity is required for cytoadherence, recombinant
      proteins show no detectable proteinase activity. These data show that recombinant
      proteins from these clones exhibited characteristics of the trichomonad adhesins.

PMID- 8555731
TI  - Phenytoin serum concentration monitoring during pregnancy and puerperium in
      Mexican epileptic women.
AB  - Phenytoin serum concentrations were evaluated in 88 epileptic women at different
      stages of pregnancy and 40 women during postnatal periods. In addition,
      concentrations were determined from the umbilical cords of 27 neonates. On
      average, the dose of phenytoin was increased by 130 +/- 54 mg in 67% of the
      patients in order to control seizures. In 76% of the women during pregnancy and
      95% in the postnatal periods, dose adjustment was achieved for the control of the
      seizures. Therapeutic clinical concentrations ( < 9.9 micrograms/ml) were found
      in 64% of the patients, with an average of 7.2 +/- 1.8 micrograms/ml during
      pregnancy and 6.2 +/- 2 micrograms/ml in 90% of the women during the postnatal
      period. The average phenytoin concentration reached with doses of 100, 200, 300,
      400 and 500 mg were 3.3, 5.7, 8.4, 10.8, and 14.1 microliters/ml, respectively,
      without statistically significant differences among the pharmacokinetic
      parameters measured during pregnancy, between pregnancy and the postnatal period.
      The proportion between fetal and maternal phenytoin concentration was 0.37 +/-
      0.28. Hydantoin fetal syndrome was seen in 8% of the neonates, without a
      statistically significant difference among patients with or without seizures. No
      relation was found between the concentration of phenytoin during pregnancy and
      the hydantoin fetal syndrome. The study shows that low concentrations of
      phenytoin can control seizures during pregnancy and the postnatal period and the
      need to relate serum phenytoin concentrations with the clinical state of pregnant
      women who suffer seizures.

PMID- 8555732
TI  - Opposite effects of breakfast vs. oral glucose on circulating androgen levels in
      healthy women.
AB  - Since certain hormone abnormalities can be food-dependent as in some cases of
      nodular adrenal hyperplasia, as a first step to study other more frequent
      endocrine disorders, using a standard meal as means of a more physiologic
      stimulus, we investigated in healthy women whether or not the changes in serum
      glucose, insulin, cortisol, and androgens are different following a breakfast
      than after oral glucose alone. Ten women (group 1) ingested a 725 kilocalories
      (173 kiloJoules) breakfast and ten women (group 2) ingested a 100-g glucose load
      at 8:00 A.M. Serum glucose, insulin, cortisol, dehydroepiandrosterone sulfate
      (DHEAS), free testosterone (free-T), and androstenedione (A) were determined
      every 30 min for the next 2 h. Serum glucose rose higher in group 2 than in group
      1 (p < or = 0.05), yet insulin increased similarly in both groups. In group 1
      free-T and DHEAS increased at 30 min (p < or = 0.05) while cortisol decreased (p
      < or = 0.04); A did not change. On the contrary, in group 2 only a decrease in
      free-T (p < or = 0.01) was detected. In these healthy women, serum androgen
      changed inversely depending on the type and composition of the oral stimulus
      used. The simultaneous increase of serum insulin, free-T and DHEAS coinciding
      with a cortisol decrease may enhance insulin anabolic effects following
      breakfast, but not after oral glucose alone.

PMID- 8555733
TI  - Effects of propofol on alterations of multineuronal activity of limbic and
      mesencephalic structures and neurological deficit elicited by acute global
      cerebral ischemia.
AB  - The increment of GABAergic inhibitory activity, the reduction of metabolic rate
      and oxygen consumption induced by propofol on the neuronal components of brain
      structures, and its antioxidant potential have supported the possible beneficial
      effects of this drug against brain damage elicited by cerebral ischemia.
      Multineuronal activity (MUA) and EEG from mesencephalic reticular formation,
      hippocampus, and amygdala, and EEG from the parietooccipital cortex were recorded
      and analyzed during vehicle or propofol, 0.25 mg/kg/min i.v., administered during
      a 6 h period following a 10 min cardiorespiratory arrest and 2-4 min of
      reanimation in two groups of cats under neuromuscular blockade and assisted
      ventilation. This was continued daily during alertness for 8 days after
      cardiorespiratory arrest along with determining daily neurological deficit
      scores. Mean MUA frequency, progressively increasing in subcortical structures of
      untreated cats during the hours following cardiorespiratory arrest, was
      significantly lower in propofol treated cats. A significant reduction of MUA in
      the hippocampus was then observed in the untreated but not in the propofol
      treated cats, and in amygdala in both treated and untreated cats. Alterations of
      MUA were not observed in the mesencephalic reticular formation during alertness
      on the days after cardiorespiratory arrest. Significantly lower neurological
      deficit scores were recorded in propofol treated than in untreated cats the days
      after cardiorespiratory arrest. It can be concluded that propofol is capable of
      reducing both brain electrical activity alterations in specific brain structures,
      and neurological deficit elicited by complete global cerebral ischemia in cats.
      Inhibition of MUA from limbic and mesencephalic brain structures induced by
      propofol early after global cerebral ischemia could be related to these effects.

PMID- 8555734
TI  - Clinical neurophysiological comparative study on HTLV-1 associated
      myelopathy/tropical spastic paraparesis.
AB  - In order to determine the neurophysiological characteristics of HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) throughout the world, we
      analyzed and compared the most common clinical neurophysiological studies (CNPS)
      performed in this entity from those places with a high prevalence and interesting
      regional differences were noted. African patients showed a noteworthy involvement
      of the peripheral nervous system (PNS). Chilean patients displayed a more
      circumscribed abnormality around the spinal cord. The migrants from the West
      Indies to England showed important visual, and somatosensory evoked potential
      (SSEP) alterations in the upper limbs (UL). Japanese patients also presented some
      involvement of the PNS, but their illness duration was less protracted than that
      observed in other countries. The differences found in visual pathways and PNS
      involvement among these groups were statistically significant (p < 0.05). Thus,
      this study shows not only a widespread subclinical involvement in both central
      and PNS in HAM/TSP, but also strongly supports the idea that the lesion
      distribution and progression of this disease are different among countries. Such
      differences could likely be due to the action of the so-called environmental co
      factors present in each of these areas which should be promptly investigated.

PMID- 8555735
TI  - Botulinum toxin-A for the treatment of hemifacial spasm.
AB  - Management of hemifacial spasm can actually be done medically, surgically and
      with Botulinum-A Toxin. The Botulinum-A Toxin treatment locally injected into the
      involved facial muscles offers a useful alternative to medical and surgical
      therapy. The objective of this study was to evaluate the efficacy of Botulinum-A
      Toxin for the treatment of hemifacial spasm in those subjects for whom the
      presently available medical therapy is inadequate. A total of 28 individuals were
      enrolled in the clinical study. Patients were evaluated using the Fahn's
      blepharospasm rating and disability scales. Efficacy was assessed by evaluating
      changes from the baseline in eyelid spasm intensity, brow spasm intensity, eyelid
      force and facial spasm intensity. All 28 subjects with hemifacial spasm showed
      clinical improvement in relation to this baseline, which was statistically
      significant. The mean decrease from baseline at their follow-up examination was
      statistically significant for all subjects and for all measurements: eyelid spasm
      changed from 2.3 to 0.3 (p = 0.0001); brow spasm from 1.9 to 0.1 (p = 0.0001);
      facial spasm from 2.3 to 0.1 (p = 0.0001) and eyelid force from 0.9 to -0.1 (p =
      0.0020). We concluded that Botulinum-A Toxin provides a significant therapeutic
      benefit to patients with hemifacial spasm, without the risk of disabling side
      effects.

PMID- 8555736
TI  - Carotid artery atherosclerosis in a Mexico City population with high carbohydrate
      intake.
AB  - We present the results of a population based survey designed to estimate the
      prevalence and clinical characteristics of carotid artery atherosclerosis (CAS)
      diagnosed using vascular ultrasonography (VUS) in a low income area of Mexico
      City encompassing six neighborhoods that we previously studied. We attempted to
      locate all the non-diabetic participants of the first two neighborhoods (n = 834)
      and all diabetics from the six neighborhoods (n = 304). We located 1078 (94.7%)
      participants and examined 770 (71.4%). All study subjects were men and non
      pregnant women between 35-64 years of age and had standardized VUS protocol. In
      men, the prevalence of CAS was 16.29%, in women the prevalence was 12.3%. CAS was
      significantly associated in both sexes to age (p < 0.001) and systolic blood
      pressure (p < 0.001). The ratio of the subscapular to triceps skinfolds was
      significantly higher in men with CAS (p < 0.04). In women, fasting glucose was
      higher in subjects with CAS (p < 0.04). The lipid profile was similar in men with
      and without CAS. However, women with CAS had significantly higher total
      cholesterol (p < 0.001), LDL cholesterol (p < 0.002), VLDL cholesterol (p <
      0.092) and mean TG (p < 0.033). The percent of patients with hypertension,
      tobacco use, myocardial infarction and diabetic retinopathy of any degree was
      significantly higher in the subjects with CAS. CAS of any degree was observed in
      12.4% of the non-diabetic population and 18.13% of the diabetics.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8555737
TI  - Gallstone composition in Mexican patients.
AB  - Prevalence of gallstone disease in Mexico is similar to that found in some
      European countries. Patients from those industrialized Western countries
      primarily develop cholesterol gallstones; however, we do not have information
      related to the chemical composition of gallstones in the Mexican population. The
      aim of this study was to determine the physiochemical characteristics of
      gallstones from patients undergoing surgery for symptomatic cholelithiasis. We
      analyzed gallstone specimens from 59 patients (17 male and 42 female) from five
      Mexican states and Mexico City by X-ray diffraction. The chemical analysis
      revealed that 71.2% of the patients had stones of mixed composition. We concluded
      that the chemical composition of gallstones found in Mexican patients is similar
      to that found in patients from other Western countries.

PMID- 8555738
TI  - The dopamine D2 receptor gene TaqI A1 polymorphism and alcoholism in a Mexican
      population.
AB  - The suggested association between the TaqI A1 allele of the dopamine D2 receptor
      (DRD2) gene with alcoholism was studied comparing the genotypes of 38 controls
      and 38 ethnic matched alcoholics, drawn from the Mexican population. The
      alcoholics in our sample suffered from one of the following conditions: delirium
      tremens, alcohol hallucinosis or uncomplicated alcohol withdrawal. Eighty-eight
      percent of the controls carried the A1 allele. The frequency of the DRD2 A1
      allele in the Mexican sample was higher than reported in Caucasians, but similar
      to those described in Amerindian groups. There was not any difference in the
      prevalence or allele frequency between alcoholics and controls. Also, there was
      no significant differences when alcoholics were subtyped according to severity,
      age of onset, or positive family history. Alcoholics showed higher scores than
      controls in the neuroticism and psychoticism subscales on the Eysenck Personality
      Inventory. However, no relationship between personality traits and genotypes was
      found. Our results do not support a consistent association between the D2
      receptor gene and alcoholism.

PMID- 8555739
TI  - Penicillamine produces changes in the acute blood elimination and tissue
      accumulation of thallium.
AB  - D-penicillamine (PCA) is used by some physicians in human thallium intoxication.
      With the aim of learning how the blood thallium altered kinetics and the
      modifications produced on the tissue accumulation, we administered PCA to white
      male thallium dosed rabbits. The method consisted of intravenous (i.v.)
      administration of thallium (10 mg/kg) to three groups of rabbits. The first group
      (control) received only the metal, the second group (treatment A) received PCA
      (25 mg/kg) at the 70th minute after thallium dose, the third group (treatment B)
      received the PCA at the same dose, 30 sec before the metal was administered. For
      kinetics studies, blood samples were collected in all groups at minutes 65, 70,
      71, 73, 75, 80, 85 and 90. For thallium accumulation studies, bile, urine and
      tissue samples were collected. Thallium analyses were made by atomic absorption
      spectrophotometry. The results showed that in treatment A rabbits, the blood
      thallium concentration raised significantly at the 71st and 73rd minutes.
      Concerning metal in tissues, muscle mass accumulated significantly more thallium
      by the B-treatment, while brain accumulation was significantly greater with
      treatment A. In conclusion, the PCA modifies the blood thallium elimination acute
      kinetics for a few minutes and changes its accumulation in some tissues,
      suggesting that PCA extracts the metal from tissues and then re-distributes it
      throughout the organism.

PMID- 8555740
TI  - Myoendothelial contacts in the human fetal aorta.
AB  - Intracellular communication is an essential process in both embryological
      development and for the maintenance of normal tissue physiology. We have
      established the presence of this type of communication between endothelial cells
      and vascular smooth muscle cells in man and have here investigated the close
      contacts between endothelial and smooth muscle cells in the aorta of the 10-week
      old human fetus. Transmission electron microscopy revealed myoendothelial
      contacts in the form of cytoplasmic projections, usually originating from the
      muscle cells. The nature of the cell-cell contacts was via simple appositions
      with an intercellular space of 6-15 nm. Myoendothelial contacts are sites for
      communication between elements of the intima and media, ensuring that paracrine
      secretion can occur and that the vessel wall, during growth and development,
      works as a unit.

PMID- 8555741
TI  - Molecular genetic technology transfer to pathogenic fungi.
AB  - Histoplasma capsulatum, the best fungal model for studying intracellular
      parasitism, is now becoming a model system for evaluating the molecular basis of
      virulence. This brief review summarizes the available tools and emerging
      techniques for molecular genetic studies of H. capsulatum and related fungal
      pathogens.

PMID- 8555742
TI  - Entamoeba histolytica axenic growth improvement by ox bile.
AB  - Axenic Entamoeba histolytica cultures, grown in PEHPS medium, showed increasing
      yields and growth velocity when added with 0.03 to 0.6 g/l gallbladder ox bile,
      while higher doses were toxic for amebas. The highest density (505 +/- 29 x 10(3)
      trophozoites/ml) and shortest duplication time (Dt = 10.74 +/- 0.2 h)
      corresponded to cultures added with 0.24 g bile/l. Their yields were 1.74 and
      3.34 times higher, respectively, than those which were reached by the non-added
      PEHPS controls and by growth of amebas in TYI-S-33 medium. Between 72 and 96 h of
      incubation a noticeable increase in trophozoite density was observed in cultures
      added with 0.24 g/1 bile among controls. At 72 h yields of bile-added cultures
      inoculated with 5, 10 and 20 x 10(3) amebas/ml increased in function of the
      inoculum. The improved growth of E. histolytica by adding 0.24 g/l ox bile to
      culture medium suggests that bile has compounds are essential for amebas.

PMID- 8555743
TI  - Determination of polynuclear aromatic hydrocarbons present in asphaltenes from
      Mexican oil. A possible environmental risk.
AB  - A supercritical fluid extraction and HPLC analysis of the asphaltenes derived
      from Mexican oil was performed. The aim was to identify potentially mutagenic
      polynuclear aromatic hydrocarbons present in asphaltenes, since roof
      waterproofing applications in this country present a significant exposure to hot
      asphaltene vapors that might conceivably carry such toxic hydrocarbons and
      therefore pose a health hazard to the workers who apply molten asphaltenes.

PMID- 8555744
TI  - Adrenergic ligands trigger intracellular differentiation of trypanosoma cruzi.
AB  - Intracellular forms of trypanosoma cruzi, amastigote, could remain in the inner
      space of mammalian cells for long periods of time and be in contact with various
      cellular metabolism products. Some of these metabolites could act as signals that
      trigger parasite differentiation process to trypomastigote form. The present
      results suggest that increase of intracellular cAMP by adrenergic ligands or
      cholera toxin in parasite infected cells is able to induce such differentiation
      process.

PMID- 8555745
TI  - VIIIth Congress of the European College of Neuropsychopharmacology. Venice,
      Italy, 30 September-4 October 1995. Abstracts.

PMID- 8555746
TI  - The use of opiate antagonists for recurrent self-injurious behavior.
AB  - Despite a plethora of studies on the behavioral and pharmacologic treatment of
      self-injurious behavior, and despite our best efforts, many patients continue to
      harm themselves. The authors review the literature on the use of opiate
      antagonists for the treatment of self-injurious behavior.

PMID- 8555747
TI  - Psychiatric morbidity in seizure patients on a neurodiagnostic monitoring unit.
AB  - This study aimed to clarify prevalence and type of psychiatric disorders among 97
      consecutive patients with seizures who were admitted for neurodiagnostic
      monitoring. Of the 97 patients, 33 (34%) had an atypical mood disorder, 21 (22%)
      had pseudoseizures, and 9 (9%) had other psychiatric disorders, for a total of 63
      (65%) in need of psychiatric treatment. Patients with the atypical mood disorder
      had predominantly depressive symptoms, which occurred intermittently, were
      associated with episodes of irritability, and alternated with briefer euphoric
      moods. Anxiety and phobic symptoms occurred less often. The existence of an
      epilepsy-specific mood disorder is suggested.

PMID- 8555748
TI  - Positron-emission tomography in tardive dyskinesia.
AB  - Cerebral glucose metabolic rates were determined in normal control subjects (n =
      26) and schizophrenic patients with tardive dyskinesia (n = 14). Globus pallidus
      and primary motor cortex (precentral gyrus) metabolic values divided by those of
      the cerebral hemispheres were significantly increased in the patient group. A
      similar metabolic pattern has not been reported for schizophrenic patients
      without tardive dyskinesia, and the abnormalities were demonstrated despite the
      normal appearance of the basal ganglia on X-ray CT. The findings differed
      markedly from the reduced metabolic rates of the basal ganglia previously
      identified in other choreiform disorders, including Huntington's and Wilson's
      diseases. The findings suggest that tardive dyskinesia is characterized by
      increased pallidal synaptic activity resulting from either altered
      striatopallidal input or increased pallidal interneuron firing.

PMID- 8555749
TI  - Clozapine-induced EEG abnormalities and clinical response to clozapine.
AB  - The authors hypothesized that patients who develop gross EEG abnormalities during
      clozapine treatment would have a less favorable outcome than patients who did not
      develop abnormal EEGs. The clinical EEGs and the Brief Psychiatric Rating Scale
      (BPRS) scores of 12 patients with schizophrenia and 4 patients with
      schizoaffective disorder were compared before and during treatment with
      clozapine. Eight patients developed significant EEG abnormalities on clozapine; 1
      showed worsening of an abnormal pre-clozapine EEG; none of these subjects had
      clinical seizures. BPRS scores improved significantly in the group of patients
      who developed abnormal EEGs but not in the group who did not. Findings are
      consistent with previous reports of a high incidence of clozapine-induced EEG
      abnormalities and a positive association between these abnormalities and clinical
      improvement.

PMID- 8555750
TI  - Clozapine for acute and maintenance treatment of psychosis in Parkinson's
      disease.
AB  - In a prospective, open-label study, 12 patients manifesting psychosis associated
      with Parkinson's disease were treated with clozapine. Cognitive functioning and
      type of psychotic symptoms were measured prior to treatment, and changes in
      psychiatric and behavioral symptoms were studied by using the Behave-AD Scale.
      Significant resolution in psychotic symptoms was found and improvement in global
      behavioral status observed in all cases, with 10 patients maintaining improvement
      at follow-up. Careful initiation and titration of the drug resulted in few side
      effects, and dementia was not found to be a contraindication to such treatment.

PMID- 8555751
TI  - The relationship between psychiatric symptoms and regional cortical metabolism in
      Alzheimer's disease.
AB  - Cognitive and noncognitive psychiatric symptoms were systematically evaluated in
      21 patients with Alzheimer's disease by using the Neurobehavioral Rating Scale.
      Regional cerebral metabolic activity was measured in each patient by
      [18F]fluorodeoxyglucose PET. Significant correlations emerged between global
      cortical metabolic activity and the Agitation/Disinhibition factor score,
      Cognition factor score, and total score. Relationships between noncognitive
      symptoms and metabolic activity were regionally specific, with significant
      correlations between Agitation/Disinhibition factor score and metabolism in the
      frontal and temporal lobes, between Psychosis factor score and metabolism in the
      frontal lobe, and between Anxiety/Depression factor score and metabolism in the
      parietal lobe. These results suggest that psychiatric symptoms are fundamental
      expressions of the cortical dysfunction of Alzheimer's disease.

PMID- 8555753
TI  - The Cognitive Bias Task and lateralized frontal lobe functions in males.
AB  - The Cognitive Bias Task (CBT) is a multiple-choice response selection paradigm
      characterized by inherent ambiguity. All items offer a range from extremely
      context-dependent to extremely context-invariant responses. Lateralized
      prefrontal lesions produce extreme, and opposite, response biases on CBT in right
      handed males. Healthy control subjects perform in the middle range. Findings
      suggest a dynamic balance between two synergistic decision-making systems in the
      frontal lobes: context-dependent in the left hemisphere and context-invariant in
      the right. The robust lateralized effects, which are dependent on task ambiguity,
      are sensitive and specific to frontal dysfunction. CBT is discussed in comparison
      with the Wisconsin Card Sorting Test as a potential cognitive activation task for
      functional neuroimaging of the frontal lobes.

PMID- 8555752
TI  - Increased cerebral blood flow during m-CPP exacerbation of obsessive-compulsive
      disorder.
AB  - The partial serotonin agonist m-chlorophenyl-piperazine (m-CPP) has been reported
      to increase obsessive-compulsive symptoms in some patients with obsessive
      compulsive disorder (OCD). The authors investigated the underlying physiological
      mechanisms of this variable exacerbation by imaging regional cerebral blood flow
      with the planar xenon-133 method after administration of oral m-CPP (0.5 mg/kg).
      Seven patients who responded to m-CPP with symptomatic exacerbation had a marked
      increase in global cortical perfusion (18.1%), in contrast to the remaining 7
      nonresponders to m-CPP, who showed no change. These results suggest that m-CPP
      exacerbation of OCD symptoms is associated with increased cortical blood flow.

PMID- 8555754
TI  - Successful methylphenidate treatment of apathy after subcortical infarcts.
AB  - A patient with prominent apathy secondary to multiple subcortical infarcts was
      treated successfully with methylphenidate. SPECT and reaction time testing showed
      selective improvement of frontal system function, consistent with a recent model
      of frontal-subcortical circuits and behavior.

PMID- 8555755
TI  - SPECT findings before and after ECT in a patient with major depression and
      Cotard's syndrome.
AB  - A patient's major depression and Cotard's syndrome (the delusion of being dead)
      both resolved completely after 12 ECT treatments. A SPECT study 1 week before ECT
      showed reduced blood flow in the frontoparietal medial and dorsolateral frontal
      cortex, basal ganglia, and thalamus; SPECT 1 month after ECT showed perfusion
      increments in those regions. This case study demonstrates that Cotard's syndrome
      in the context of major depression may be successfully treated with ECT and
      suggests that the psychiatric improvement was accompanied by increased blood flow
      in specific brain areas.

PMID- 8555756
TI  - Obsessive-compulsive disorder in patients with multiple sclerosis.

PMID- 8555757
TI  - Clinical applications of functional MRI in neuropsychiatry.
AB  - Clinical neuroimaging is due for yet another sea change as functional
      neuroimaging becomes increasingly powerful and available. Functional magnetic
      resonance imaging (fMRI) is perhaps the most promising of the emerging
      techniques. The following review helps us understand the physics, strengths,
      limitations, and promise of fMRI. The authors are all affiliated with the Brain
      Imaging Center at McLean Hospital and with the Departments of Neurology (Dr.
      Levin) and Psychiatry (Dr. Renshaw) at Harvard Medical School.

PMID- 8555758
TI  - The catecholamine hypothesis of affective disorders: a review of supporting
      evidence. 1965.

PMID- 8555759
TI  - HAIR-AN syndrome and mental disorders.

PMID- 8555760
TI  - [A case of dirofilariasis of the scrotum of probable origin in Languedoc].
AB  - Adult Dirofilaria (Nochtiella) repens in scrotal cavity is a rare localisation
      (likewise in others localisations). This report deals with a case occurred in
      Languedoc (about 50 cases of subcutaneous dirofilariasis were described in
      France). The localisation in scrotal cavity occurred probably after migration of
      adult female in subcutaneous tissue.

PMID- 8555761
TI  - [Mycetoma of the neck and the nape of the neck due to Madurella mycetomatis.
      Apropos of a case in Mauritania].
AB  - Fungous mycetoma of the nape of the neck due to Madurella mycetomatis is an
      unusual localisation (four cases in mondial literature) and severe affection.
      This reports deals with a case occurred after traumatism. Despite five months of
      itraconazole and chirurgical treatment, the therapeutic escape was evident.

PMID- 8555763
TI  - [A note on Psorophora lineata (Humboldt, 1819) (Diptera, Culicidae) in French
      Guiana].
AB  - Psorophora lineata, a very large-sized mosquito, has rarely been collected in
      French Guiana. From specimens obtained in 1942-1991, data on morphology,
      bionomics, local distribution and disease relations are given. P. lineata may be
      considered as a potential vector of arboviruses.

PMID- 8555762
TI  - [Secondary effects of the treatment of hypermicrofilaremic loiasis using
      ivermectin].
AB  - In the last ten years ivermectin appeared an efficient and safe alternative to
      diethylcarbamazine which is known to induce severe adverse reactions in loiasis,
      including encephalitis. After these results, large scale ivermectin treatments
      against onchocerciasis were carried out in Central Africa where loiasis is also
      endemic; and seven cases of severe reaction were reported in Cameroon since 1991,
      during these mass ivermectin treatments. In order to study adverse reactions in
      patients harbouring high load of Loa loa microfilariae (mf), we realized careful
      hospital based treatment in 112 patients with more than 3,000 mf/ml (ml) blood.
      Patients received once 200 micrograms ivermectin per kilogram at day 0 (D0).
      Clinical examination was made daily during the four following days (D1 to D4).
      Blood and urine samples were analysed before treatment and at D1 and D3. Lumbar
      puncture was made at D1 for 39 patients with more than 10,000 mf/ml; at D3 for
      the 49 following patients without consideration for the level of parasitaemia,
      and at D0 and D3 for ten voluntary patients. For analysis the patients were
      distributed in 3 groups according to initial parasitaemia: the first group
      included 50% out of the patients, those whose parasitaemia was fewer than 15,000
      mf/ml blood; the second group included 25% patients whose parasitaemia was
      between 15,000 and 30,000 mf/ml; the third group included the last 25% patients
      whose parasitaemia was higher than 30,000 mf per ml blood. Adverse reactions were
      observed in 71% out of the patients. Symptoms described were fever, pruritus,
      headache, arthralgia. Most symptoms appeared 24 to 36 hours after treatment.
      Temperature increased significantly in group 3. Microfilaraemia decreased by 85%
      in the 3 groups during the 4 days following treatment. C-reactive-protein
      increased dramatically after treatment in all patients (p < 10(-4)). Some
      patients presented blood in urine in three groups but haematuria reached 35% of
      patients in group 3. Proteinuria is noted among 33% of all patients but 20% in
      group 1 and 2 versus 70% in group 3. Loa loa mf were observed in urine of half
      the patients, but in low amounts (< 10 mf per 50 ml urine). In cerebro-spinal
      fluid (CSF), some mf appeared at D1 or D3 in people heavily infected with Loa
      loa, reaching 80% of the patients of group 3. LP made at D0 in ten patients with
      parasitaemia higher than 30,000 mf/ml blood confirmed that CSF was naturally
      microfilaria free before treatment. One patient presented severe troubles with
      fever, asthenia and conscience troubles beginning at D3, reactive coma at D4,
      renal impairment with transitory anuria; progressive improvement in 2 weeks and
      complete recovery at D22; he presented 102 mf/ml CSF at D6. The study confirmed
      that ivermectin treatment is generally well tolerated. Among people with high Loa
      loa parasitaemia the symptoms after treatment are frequent but mild. However
      severe cases with conscience troubles are possible, and may occur in about 1% of
      subjects with more than 3,000 mf/ml blood. Severity of adverse reactions was
      linked to level of parasitaemia before treatment. The critical parasitaemia level
      which could lead to expect serious adverse effects seems to be 30,000 ml/ml
      blood. These informations should induce carefulness to carry out large scale
      treatments against filariosis in endemic areas of Loa loa.

PMID- 8555764
TI  - [The prevalence of anti-hepatitis C antibodies in pregnant women and blood donors
      in Benin].
AB  - In order to precise if the hepatitis C virus (HCV) represents a potentially
      important infection for public health in Benin, the authors have studied the
      seroprevalence rate of this virus in august 1991, among two groups of population
      in Cotonou: 349 donors of blood (including 321 males); mean of ages: 28.7 y.-o.,
      149 pregnant women (mean of ages: 24.5 y.-o.). They have used an ELISA test
      (Innotest HCV Innogenetis NV, Antwerpen, Belgium) and retested the positive
      serums by LIA (Line Immuno Assay, Inno LIA HCV). A serum reacting with at least
      one peptide has been considered as positive. In the donors of blood and the
      pregnant women, a prevalence rate of respectively 2.3% (+/- 1.2) and 0.7% (+/-
      0.9) has been established. These rates are worthy to be compared to those
      reported in Niger among the same types of population and with the same serologic
      tests. They are much inferior to those noted in East Gabon or South Cameroon:
      respectively 6.5% and 9.8%. This preliminary study has to be enlarged by
      investigations, which may precise the consequences of HCV presence in Benin for
      public health in this country.

PMID- 8555765
TI  - [Post-vaccination anti-poliomyelitis seroprevalence in an urban setting in
      Abidjan].
AB  - In order to determine the antipoliomyelitis seroprevalence of children in
      Abidjan, we checked the presence of antipoliovirus antibodies in 48 children
      received in the South Abobo's vaccination center for vaccination against measles.
      According to the vaccination schedule and rules applied in Cote d'Ivoire: 12.5%
      of the children have received less than three doses or oral polio vaccine (OPV),
      87.5% have received the three doses. Antibody titration results indicated that
      78.6, 93 and 76.2% of the children have been immunized against Poliovirus type I,
      type II and type III, respectively; 71.4% of the children showed antibodies
      against the three poliovirus serotypes and 4.8% had no antipoliovirus antibodies
      at all. The children which showed an antibodies titer less than 1/8 were
      considered unprotected: the proportion of unprotected was 21.4, 7 and 23.8%
      against Poliovirus type I, type II and type III, respectively. Although these
      results showed that the level of protection against poliomyelitis in Abidjan is
      acceptable (> 75%), the efforts for vaccination program in Cote d'Ivoire need to
      be improved in order to eradicate poliomyelitis.

PMID- 8555766
TI  - [The seroprevalence of human immunodeficiency virus infection (HIV) in patients
      with tuberculosis at the National Hospital of Niamey, Niger (1990-1991)].
AB  - This study has been planned in order to determinate the frequency of the
      infection by VIH among the 394 new tuberculous, for a period extended from July
      1990 to July 1991 at the section of pneumophtisiology in the National Hospital of
      Niamey. The number of seropositives is 7.6%. The two types of viruses, i.e. VIH1
      and VIH2, and the double infection by VIH1 + VIH2 types exist in the tuberculous
      patients. The VIH1 is most frequently found in the subjects of age group 20-39
      years, who are almost emigrants. Inspite of the actual weak sero-prevalency among
      the tuberculous patients, the authors claim that a sero-epidemiological
      sequential survey of tuberculosis in Niamey can be a relatively easy method for
      measuring the variations of sero-prevalency of AIDS in Niger.

PMID- 8555767
TI  - [The seroprevalence of human immunodeficiency virus infection (HIV) in the
      Touaregs and Peuls Bororo in Niger].
AB  - A seroepidemiological study of endemic treponematosis (bejel) in Niger allows us
      to realise an anonymous non correlated screening of VIH infection in Nomads:
      Touaregs of Tchirozerine (Agadez), Peuls Boro of Bermo (Maradi). On the 424
      Touaregs screened only one was seropositive to VIH2 infection confirmed with
      Western blot that means 0.23% of seroprevalency comparable to that 0.50% found in
      the general population. The seroprevalency of trepronematosis (VDRL + TPHA+) is
      7% in the range of 5 to 15 years old (80%), period which corresponds to the
      transmission of Bejel. Moreover this population don't travel to the seaborder
      countries. Concerning the 213 of the Peuls Bororo screened we had only 3
      undetermined reactions to Western blot 1 and 2, despite the high seroprevalence
      of the treponematosis (VDRL+ TPHA+): 22% mostly in the subjects of more than 15
      years old (89.36%) which is the sexual intercourse and exodus period to the
      seaborder countries, where 66% of our VIH patients are infected.

PMID- 8555768
TI  - [Seroprevalence of rickettsial infections of the Boutonneuse fever group or its
      apparent group in Bangui (Central African Republic)].
AB  - 115 sera from African individuals, including 66 HIV-1-infected individuals and 49
      HIV-seronegative age-matched healthy controls, living in Bangui, Central African
      Republic, were screened for Rickettsia conorii antibody by indirect
      immunofluorescent assay; 53 (46%) sera had significant IgG to R. conorii titer,
      and 5 (4.3%) had significant IgM to R. conorii titer, without significant
      difference between HIV-positive and negative individuals. These findings indicate
      a great exposure to spotted fever group rickettsial infections in Bangui.

PMID- 8555769
TI  - [Comparison between various methods of pregnancy screening during a large-scale
      ivermectin treatment in Cameroon].
AB  - During a mass treatment with ivermectin which is contraindicated to pregnant
      women, authors made a screening for pregnancy by questioning 2,580 women from 15
      to 45 years old. 1,409 of these women were also interrogated by a female
      physician assisted by a native matron to detect pregnant women. In 1,798 women,
      at least one immunological pregnancy test has been used in the field. A nine
      months follow-up was made to check answers. Women's knowledge led to a good
      appreciation of pregnancy as they correctly appreciated their pregnancy from the
      second month: specificity was good (98%) but sensitivity was moderate (71%).
      Conclusions made by gynecological team after detailed questionnaire were more
      sensitive (80%), but specificity decrease dramatically to 59%. Combinations of
      several items in the questionnaire showed no benefit. Sensitivity of the various
      immunological pregnancy tests tried was included in 70 to 90% and specificity was
      varying from 87 to 97%. Simple questioning of women was the most efficient method
      (efficiency value was 94% against 63% for interview and 92% for pregnancy tests).
      However, the use of this method induced the risk that about 29% of women have
      been treated although they were pregnant.

PMID- 8555770
TI  - [Malaria among expatriates in Brazzaville (Congo)].

PMID- 8555771
TI  - [Intra-family transmission of human T-cell lymphotropic virus-1 (HTLV-1) in a
      cohort of HTLV-1-positive patients (Benin)].
AB  - We are reporting the results of a familial study carried out in Benin in March
      1994 within a cohort of HTLV-1 positive subjects. This study aims at appraising
      the different modes of intra-familial transmission of this retrovirus. The study
      has included 212 persons: 33 seropositive subjects (identified during two
      previous seroprevalence surveys and followed up since 1991), and 179 members of
      their families. Blood specimens have been taken from each of these subjects. Sera
      have been screened for HTLV-1 antibodies by ELISA test and positive results
      confirmed by Western blot test. Out of 18 children born during the follow up
      period, 2 cases of seroconversion have been observed. One case of seroconversion
      has also been noted among the 17 couples in which either of the spouses is
      seropositive. Among the 136 children of the cohort: 17.8% of them are HTLV-1
      positive when both parents are seropositive 26.1% if the mother only is
      seropositive and 0% if the father only is seropositive. The incidence rate in
      this cohort is estimated to be 0.43%. These data relative to the intra-familial
      transmission of HTLV-1 in Benin appear to be consistent with those previously
      reported in Japan.

PMID- 8555772
TI  - [Tick-transmitted arbovirus in Maghreb].
AB  - The problem of arbovirus infections in Maghreb has been relatively neglected in
      the pst in spite of a rich diversity of biotopes, the presence of potential
      reservoirs and vectors, and their position on the flight path of the Palearctic
      african bird migration systems, western branch. Moreover, West Nile virus has
      been isolated from southern Algeria since 1968. From 1979 to 1989, ticks were
      collected from wild birds, pigeons, bats, rodents, poultry, camels, wild boars,
      domestic mammals and man, and assayed for viruses. On the whole, 424 ticks were
      virologically studied from Morocco, 582 from Algeria and 601 from Tunisia. Four
      tick-borne arboviruses have been isolated so far: three from Morocco, Soldado
      (Nairovirus), Essaouria (Orbivirus) and Kala Iris (Orbivirus) from Ornithodoros
      (A.) maritimus ticks parasitizing marine birds, and one from Tunisia, Tunis
      (Phlebovirus), from Argas reflexus hermanni infesting domestic pigeons. Soldado
      virus may infect man working into colonies of gulls for ornithological or
      entomological purposes and this infection is associated with a self-limited
      febrile illness and pruritus. In addition, antibody to Essaouira virus was
      detected in a wild rodent in Morocco. On the contrary it is unlike that Tunis
      virus may infect man because A. r. hermanni is a strickly ornithophilic tick.
      However, Uukuniemi group antibody has been previously evidenced in wild rodents
      in Tunisia. Finally, it is not excluded that other, more pathogenic, arboviruses
      such as Congo-Crimean haemorrhagic fever might be accidentally introduced in this
      sensitive geographical area.

PMID- 8555773
TI  - [Human external ophthalmomyiasis: a bibliographic review apropos of cases in the
      Republic of Djibouti].
AB  - Ophtalmomyiasis externa was observed in Djibouti Republic. A literature survey of
      agents indicates that sheep nasal bot fly larvae, Oestrus ovis, are frequent in
      many countries. Unusual case of oral or nasal infections are indicated.

PMID- 8555774
TI  - [Is human Dirofilaria (Nochtiella) repens parasitosis mor frequent than it
      appears on the Mediterranean coast?].
AB  - Some observations of human parasitism by Dirofilaria (Nochtiella) repens are
      frequently enough reported but they are also individually reported by different
      authors. Nimes's geographical situation makes of it a privileged observatory for
      this helminthiasis. The worm's maturity varies depending on the subjects: the
      sensitivity of those and the clinical reactions are of a large variety. The ones
      that seem to be constant are the parasit's migrations in the different
      territories during a lot of months. It is the case in the observation reported
      here; in another article, we have shown the possibility of an intraperitoneal
      migration which discovery can be only of an extreme fate. Next to some noisy
      manifestations, other cases stayed quiet advise the adaptation of some
      autochtones submissed to iteratif infestations.

PMID- 8555775
TI  - [Pulmonary abscess in Lome. Apropos of 144 cases collected in the Pneumo
      Phthisiology Department of the University Hospital Center-Tokoin from 1981-1993].
AB  - The authors report the results of a retrospective study of 144 cases of lung
      abscess observed in the Pneumo-Phthisiology Department of Tokoin University
      Teaching Hospital of Lome (Togo) between 1981 and 1993 for to determine
      epidemiological, clinical, therapeutical and evolutive aspects of this affection
      on West Africa. The results like those of other authors confirm still grievous
      evolution nowadays of lung abscess in spite of medical drugs efficacy.

PMID- 8555776
TI  - [Thyroglossal duct cysts. Apropos of 17 cases in the National Hospital Center in
      Ouagadougou, Burkina Faso].
AB  - The thyroglossal duct cysts originate from thyroglossal duct involution default.
      The case record of 17 patients admitted for that disease in the ORL department of
      the national hospital of Ouagadougou during those past 7 years, is reviewed. They
      represent 1.5% of patients operated in this department during the same period,
      all diseases concerned. In the present report, the thyroglossal duct cysts are
      essentially observed in children under 10 years old (13/17 patients). In most of
      the cases (12/17), our patients have needed medical advice for an anterior
      cervical tumefaction 7 years after the first symptoms. Between clinical and
      paraclinical findings we give preference to the first ones that can avoid, in
      most of the cases, a lot of complementary tests which are of limited interest and
      too expensive in our countries. In the therapeutic field, the Sistrunk technic
      has been recognized since 1920 as the best method. Our patients who have been
      operated according to that technic have no tendency to relapse.

PMID- 8555777
TI  - Filtered plasma as a potential cause of clinical misdiagnosis: inappropriate
      testing in a haematology laboratory.
AB  - We have identified situations in which filtered plasma is provided to the
      laboratory for combined assessment of lupus anticoagulant, as well as other
      diagnostic haemostasis laboratory procedures. On the basis of laboratory
      investigation, however, we report that significant errors in test result
      interpretation can arise should this occur and depending on the specimen
      processing procedure, and whether filtered plasma is used for multiple assays.
      Citrated plasma samples were obtained from 12 normal individuals and a portion of
      each sample filtered using a standard 0.22 micron filter. Small volumes were
      frozen for later analysis. We could detect a statistically significant difference
      (P < 0.01) between filtered plasma and non-filtered plasma in most test results.
      Most notable were changes in the APTT, fibrinogen, FVIII and vWF, where results
      often fell outside the normal reference range of the assay. Such assay results
      closely mimic those obtained with type 2 von Willebrand's disease (vWD) patients,
      thus should filtered plasma unknowingly be tested for vWF, a wrong conclusion of
      type 2 vWD could easily arise. Assay results for other parameters may similarly
      draw incorrect conclusions, such as mild haemophilia A and dysfibrinogenaemia. In
      summary, we report that following filtration not only are a variety of
      coagulation test results altered, but reduced plasma levels of some coagulation
      factors could potentially lead clinicians incorrectly to diagnose congenital or
      acquired deficiencies or defects. We recommend that laboratories note that (other
      than for lupus anticoagulant) filtered plasma is not appropriate for the
      coagulation laboratory, and that any abnormal haemostasis test result following
      such combined testing be considered a potential artifact and independently
      repeated to confirm any putative abnormality prior to drawing any clinical
      conclusions.

PMID- 8555778
TI  - Expression of cell-surface lectins on haemopoietic progenitor cells.
AB  - The expression of lectins on the surface of the murine multi-myeloid progenitor
      cell line FDCP-Mix, and the human leukaemic cell line KG1, was assessed and
      compared to the pattern of lectin expression observed on human bone marrow
      mononuclear cells. Using flow cytometry, cell-surface lectins were identified by
      their ability to recognise fluorescein isothiocyanate-labelled neoglycoproteins.
      Both cell lines recognised neoglycoproteins expressing alpha-D-glucose and alpha
      D-galactose residues. Inhibition studies suggested that recognition of these
      neoglycoproteins was via two independent receptors, each displaying
      characteristic sugar-binding properties. The CD34+ population of bone marrow
      mononuclear cells, identified by positive staining with the anti-CD34 antibody
      QBend10, were shown to interact with alpha-glucose-, alpha-galactose- and alpha-D
      mannose-expressing neoglycoproteins. Similarly, binding of these probes to
      lymphocyte and monocyte sub-populations of CD34- bone marrow mononuclear cells
      was observed. In contrast, CD34- granulocytic cells did not appear to recognise
      these probes. It is suggested that the alpha-D-galactose binding activity
      observed for both cell lines and the alpha-D-galactose and alpha-D-mannose
      binding activity observed for bone marrow mononuclear cells represent expression
      of the component polypeptides of the previously reported galactosyl/mannosyl
      receptor. The glucosyl-specific receptor, observed on both cell lines and on bone
      marrow mononuclear cells, has not been reported previously. It is suggested that
      this receptor may mediate glucose transport or cell adhesion through recognition
      of glucosyl-containing compounds such as heparan sulphate.

PMID- 8555779
TI  - Bleomycin-induced DNA damage and repair in wild-type and thymidine kinase
      deficient Friend mouse erythroleukaemia cells.
AB  - In this paper the DNA damage and repair induced by the radiomimetic agent
      bleomycin are compared in murine Friend erythroleukaemia wild-type 707 cells and
      a thymidine kinase-deficient sub-clone BUF. Comparisons are made using results
      obtained from the alkaline comet assay and unscheduled DNA synthesis experiments.
      Further analysis to determine the fidelity of bleomycin-induced repair as
      indicated by mutagenesis to hypoxanthine-phosphoribosyltransferase deficiency was
      also conducted. Similar sensitivities to bleomycin treatments were observed in
      the two cell types with the comet assay, while similar levels of dose-dependent
      excision repair following bleomycin treatments were also detected in unscheduled
      DNA synthesis experiments. Comet assay and unscheduled DNA synthesis experimental
      results are in agreement. Survival and induced hypoxanthine
      phosphoribosyltransferase mutant frequencies were observed to be unaffected by a
      thymidine kinase-deficiency in Friend erythroleukaemia cells. The results of this
      investigation suggest no overall difference in the repair capacities or the
      repair fidelity of Friend 707 relative to BUF cells following bleomycin
      treatments.

PMID- 8555780
TI  - Automated blood grouping by gel technology.
AB  - The ID-Sampler II, an automated liquid handling system, is designed specifically
      for use with current gel technology. It was found to be reliable, easy to use and
      fully alarmed, making it a 'walk-away' instrument. Over a three-month period
      samples for ABO/Rh(D) grouping, antibody screening and compatibility testing were
      tested in parallel with our routine microtitre plate and gel techniques. No
      ABO/Rh(D) errors occurred on the automated system and antibody screening results
      were comparable to our routine methods.

PMID- 8555781
TI  - Peptic ulcers and gastric cancer.
AB  - It is now believed that a large proportion of peptic ulcers, and possibly some
      gastric cancers, are initiated by infection with Helicobacter pylori. The natural
      habitat of this bacterial organism is the stomach, and in some populations its
      presence is ubiquitous. The mode of transmission of the organism is unclear but
      is believed to be primarily by the faecal-oral route. With improved living
      standards in developed countries infection rates, particularly in children,
      appear to be decreasing. Formerly, a commonly accepted explanation for the
      production of peptic ulcers was excess acid production. The rationale of
      treatment was to limit acid production or to protect the surface from damage.
      These treatments can be very effective, but once the treatment course is stopped
      the damage is likely to recur. The recognition that most cases of peptic ulcer
      are probably initiated by H. pylori has resulted in new treatments designed to
      eradicate the organism. This can be very effective and lead to permanent cure,
      but currently there are problems concerning response rates and increasing
      resistance by the organism. Gastric cancers are the result of a sequence of
      changes, some of which may be initiated by H. pylori. Even if it were possible,
      the eradication of H. pylori will not completely remove the public health problem
      of either peptic ulcers or gastric cancer. The rarer adenocarcinoma of the cardia
      is produced independently of infection by the organism and is increasing in
      incidence.

PMID- 8555782
TI  - Physiology and biochemistry of Helicobacter pylori.
AB  - Since Helicobacter pylori was first isolated in 1982, a tremendous amount of work
      has been carried out on the pathogenic effects of the organism and latterly on
      its physiology, nutrition and biochemistry. It is a microaerophilic Gram-negative
      bacillus that is catalase- and oxidase-positive and expresses superoxide
      dismutase. High levels of urease are produced, the activity of which can be used
      in the identification of the organism and the infected state. Other noted
      features include the production of a cytotoxin and an associated protein (CagA).
      The bacterium is the major aetiological agent in the development of chronic
      active gastritis, gastric and duodenal ulcers, gastric adenocarcinomas and mucosa
      associated lymphoid tissue lymphoma of the stomach. To gain a more complete
      understanding of how H. pylori causes disease a detailed knowledge of its
      biochemistry, physiology and nutrition is required.

PMID- 8555783
TI  - Primary gastric lymphoma.
AB  - The histopathology of low-grade primary gastric lymphoma re-capitulates the
      structure of Peyer's patches (mucosa-associated lymphoid tissue--MALT) rather
      than lymph nodes, characterised by an increased frequency of trisomy 3. Gastric B
      cell lymphoma shows a favourable clinical behaviour, possibly as its growth
      appears to be influenced by a local antigen in the form of Helicobacter pylori.
      There is no lymphoid tissue in the normal stomach, but lymphoid tissue
      accumulates in gastric mucosa almost exclusively as a consequence of H. pylori
      infection, which has MALT characteristics, and H. pylori is found in over 90% of
      cases of gastric MALT lymphoma. Laboratory studies have shown that the growth of
      tumour cells from low-grade gastric lymphomas can be stimulated by H. pylori, and
      that the effect is strain-specific and mediated by contact-dependent help from H.
      pylori-specific T-cells. Cases of low-grade gastric lymphoma, when confined to
      the mucosa, may regress following eradication of H. pylori from the patient's
      stomach. It remains to be shown whether deeply penetrating or high-grade tumours
      will respond in the same way. Other outstanding questions relate to the optimum
      interval between eradication of H. pylori and final evaluation and expected
      duration of the response. Based on these laboratory and clinical findings it is
      possible to suggest a scheme for the pathogenesis of gastric MALT lymphoma.

PMID- 8555784
TI  - Detection of red cell antibodies: current and future techniques.
AB  - The techniques used routinely in blood group serology for detection of
      antigen:antibody reactions rely on haemagglutination caused by the ability of
      antibodies, or antibody:antibody complexes to cross-link with individual cells.
      The anti-human globulin technique has become the most important test for
      detecting significant red cell antibodies; however, the classical tube test has
      been refined to improve speed and sensitivity with the introduction of microtube
      (column) agglutination and solid-phase methods. Historically, clinical
      laboratories in the UK have used albumin and/or enzyme methods to support the
      antiglobulin technique but the cost of these, the insensitivity of albumin
      techniques, and the doubtful clinical relevance of antibodies detected only by
      enzyme methods have led to a re-assessment of their value. Although recent
      innovations employing polybrene and polyethylene glycol have not become
      widespread in routine practice, the simplicity and sensitivity of microtube and
      solid-phase methods have ensured that they are becoming the commonly used
      techniques.

PMID- 8555785
TI  - Determination of aflatoxins in groundnut meal by high-performance liquid
      chromatography: a comparison of two methods of derivatisation of aflatoxin B1.
AB  - A comparison has been made between pre-column and post-column derivatisation of
      aflatoxin B1 (AFB1) during estimation by high-performance liquid chromatography
      of this toxin in groundnut meal. The effect of the use of different
      derivatisation reagents on the quantification of aflatoxin B2 (AFB2) has also
      been evaluated. Both AFB1 and AFB2 were analysed at eight levels of artificial
      contamination. Five replicate analyses were carried out at each level on both
      groundnut meal extract (acetone-water, 85:15, v/v) and extraction solvent alone.
      A statistical evaluation of the results gave limits of detection of 1.1 and 0.3
      micrograms/kg for AFB1 and AFB2 respectively, using pre-column derivatisation
      compared with 1.5 and 0.8 micrograms/kg for the post-column method. Recoveries of
      over 90% from the spiked groundnut meal extracts were achieved for both
      derivatisation methods.

PMID- 8555786
TI  - Detection of the heat-stable toxin coding gene (ST-gene) in enterotoxigenic
      Escherichia coli: development of a colour amplified PCR detection system.
AB  - Screening biological samples using the polymerase chain reaction (PCR) has
      obvious advantages compared with current molecular analytical methods based on
      gel electrophoresis and/or hybridisation, both of which are expensive and time
      consuming, therefore the development of a PCR assay format that is applicable to
      large sample numbers and that can readily use equipment commonly found in
      diagnostic laboratories would be advantageous. This report describes the
      development of a colour amplified PCR detection system which is simple in design
      and could be universally applied to the detection of any DNA template. As an
      example, the system has been applied in the detection of the heat-stable toxin
      coding gene (ST-gene) from enterotoxigenic Escherichia coli (ETEC). The assay is
      sensitive, detecting 10 fg of a purified DNA template and 270 cfu of an ST-gene
      positive ETEC strain.

PMID- 8555787
TI  - Bacterial capsules: a simple method for demonstration under the light microscope.
AB  - It is sometimes desirable to demonstrate bacterial capsules during the routine
      examination of clinical isolates. Apart from the Indian ink method, methods of
      demonstrating bacterial capsules are not only tedious but are often non
      reproducible. A combined positive-negative capsule staining procedure which is
      simple, rapid and reproducible is described.

PMID- 8555788
TI  - Platelet count and platelet factor 3 (PF-3) availability in sickle cell disease.
AB  - In view of the effect of red blood cell membrane on platelet factor 3 release in
      sickle cell disease, platelet count and platelet factor 3 (PF-3) availability
      were measured in 30 sickle cell patients in a stable state and 15 with
      thrombocytosis, and these were compared with 60 non-sickle cell individuals as
      controls. There were no significant differences in platelet counts, but there was
      a slightly higher PF-3 availability in sickle cell patients not in crisis than in
      the controls (P < 0.025). Sickle cell patients with thrombocytosis made PF-3
      available more readily than did the control individuals and sickle cell patients
      not in crisis (P < 0.001). We conclude that sickle cell patients are capable of
      making platelet factor 3 readily available for coagulation activation, and this
      may play a decisive role in vaso-occlusive crisis.

PMID- 8555789
TI  - Immunohistochemical staining followed by bleaching of melanin: a practical method
      for ophthalmic pathology.

PMID- 8555791
TI  - The future of breast and ovarian cancer clinics.

PMID- 8555790
TI  - Selegiline in Parkinson's disease.

PMID- 8555792
TI  - Delayed childbearing.

PMID- 8555793
TI  - Infertility and the NHS.

PMID- 8555794
TI  - Developing Britain's police surgeon service.

PMID- 8555795
TI  - Cochlear implantation.

PMID- 8555796
TI  - Third generation oral contraceptives--the controversy.

PMID- 8555797
TI  - Science throws light on HIV suppression.

PMID- 8555798
TI  - Canadian bill could hurt confidentiality.

PMID- 8555800
TI  - Expert group finds no evidence for cot death theory.

PMID- 8555799
TI  - Israeli doctors and patients face conflict.

PMID- 8555801
TI  - Screening to prevent renal failure in insulin dependent diabetic patients: an
      economic evaluation.
AB  - OBJECTIVE: To examine the conditions necessary to make screening for
      microalbuminuria in patients with insulin dependent diabetes mellitus cost
      effective. DESIGN: This economic evaluation compared two strategies designed to
      prevent the development of end stage renal disease in patients with insulin
      dependent diabetes with disease for five years. Strategy A, screening for
      microalbuminuria as currently recommended, was compared with strategy B, a
      protocol in which patients were screened for hypertension and macroproteinuria.
      INTERVENTION: Patients identified in both strategies were treated with an
      angiotensin converting enzyme inhibitor. SETTING: Computer simulation. MAIN
      OUTCOME MEASURES: Strategy costs and quality adjusted life years (QALYs).
      RESULTS: The model predicted that strategy A would produce an additional 0.00967
      QALYs at a present value cost of $261.53 (1990 US$) per patient (or an
      incremental cost/QALY of $27,041.69) over strategy B. The incremental cost/QALY
      for strategy A over B was sensitive to several variables. If the positive
      predictive value of screening for microalbuminuria (impact of false label and
      unnecessary treatment) is < 0.72, the effect of treatment to delay progression
      from microalbuminuria to macroproteinuria is < 1.6 years, the cumulative
      incidence of diabetic nephropathy falls to < 20%, or > 64% of patients
      demonstrate hypertension at the onset of microalbuminuria, then the incremental
      costs/QALY will exceed $75,000. CONCLUSION: Whether microalbuminuria surveillance
      in this population is cost effective requires more information. Being aware of
      the costs, recommendation pitfalls, and gaps in our knowledge should help focus
      our efforts to provide cost effective care to this population.

PMID- 8555802
TI  - Improved survival in homozygous sickle cell disease: lessons from a cohort study.
AB  - OBJECTIVE: To examine whether simple interventions in a sickle cell clinic
      improve survival in sickle cell disease. DESIGN: Survival curve analysis and
      hazard ratios in a cohort study followed from birth. SETTING: MRC Laboratories
      (Jamaica) at the University of the West Indies, and Victoria Jubilee Hospital,
      Kingston, Jamaica. SUBJECTS: 315 patients with homozygous sickle cell disease
      detected during the screening of 100,000 consecutive non-operative deliveries
      between June 1973 and December 1981 at the main government maternity hospital,
      Kingston, Jamaica. INTERVENTIONS: Prophylactic penicillin to prevent pneumococcal
      septicaemia, parental education in early diagnosis of acute splenic
      sequestration, close monitoring in sickle cell clinic. MAIN OUTCOME MEASURES:
      Survival. RESULTS: Survival appeared to improve, the log rank test for trend
      comparing the first, second, and last third of the study reaching borderline
      significance (P = 0.05). Combined deaths from acute splenic sequestration and
      pneumococcal septicaemia-meningitis declined significantly (test for trend, P =
      0.02). CONCLUSION: Early diagnosis and simple prophylactic measures significantly
      reduce deaths associated with homozygous sickle cell disease.

PMID- 8555803
TI  - Comparison of therapeutic effects and mortality data of levodopa and levodopa
      combined with selegiline in patients with early, mild Parkinson's disease.
      Parkinson's Disease Research Group of the United Kingdom.
AB  - OBJECTIVE: To compare effectiveness of levodopa and levodopa combined with
      selegiline in treating early, mild Parkinson's disease. DESIGN: Open, long term,
      prospective randomised trial. SETTING: 93 hospitals throughout United Kingdom.
      SUBJECTS: 520 patients with early Parkinson's disease who were not receiving
      dopaminergic treatment. INTERVENTIONS: Treatment with levodopa and dopa
      decarboxylase inhibitor (arm 1) or levodopa and decarboxylase inhibitor in
      combination with selegiline (arm 2). MAIN OUTCOME MEASURES: Assessments of serial
      disability, frequency and severity of adverse events, and deaths from all causes.
      RESULTS: After average of 5-6 years' follow up, mortality ratio in arm 2 compared
      with arm 1 was 1.57 (95% confidence interval 1.09 to 2.30), and difference in
      survival between the two arms was significant (log rank test, P = 0.015). Hazard
      ratio adjusted for age and sex was 1.49 (1.02 to 2.16), and after adjustment for
      other baseline factors it increased to 1.57 (1.07 to 2.31). Patients in arm 1 had
      slightly worse disability scores than those in arm 2, but differences were not
      significant. Functionally disabling peak dose dyskinesias and on/off fluctuations
      were more frequent in arm 2 than arm 1. During the trial the dose of levodopa
      required to produce optimum motor control steadily increased in arm 1 (median
      daily dose 375 mg at 1 year and 625 mg at 4 years), but median dose in arm 2 did
      not change (375 mg). CONCLUSIONS: Levodopa in combination with selegiline seemed
      to confer no clinical benefit over levodopa alone in treating early, mild
      Parkinson's disease. Moreover mortality was significantly higher with combination
      treatment, casting doubts on its chronic use in Parkinson's disease.

PMID- 8555804
TI  - Cancers coinciding with childbearing: delayed diagnosis during pregnancy?

PMID- 8555806
TI  - Magnetic resonance imaging of the knee: direct access for general practitioners.

PMID- 8555805
TI  - Health checks and coronary risk: further evidence from a randomised controlled
      trial.
AB  - OBJECTIVE: To determine the effectiveness of a health check and assess any
      particular benefits resulting from feedback of plasma cholesterol concentration
      or coronary risk score, or both. DESIGN: Randomised controlled trial in two
      Glasgow work sites. SUBJECTS: 1,632 employees (89% male) aged 20 to 65 years.
      INTERVENTIONS: At the larger work site, (a) health education; (b) health
      education and feedback on cholesterol concentration; (c) health education and
      feedback on risk score; (d) health education with feedback on cholesterol
      concentration and risk score (full health check); (e) no health intervention
      (internal control). At the other work site there was no health intervention
      (external control). MAIN OUTCOME MEASURES: Changes in Dundee risk score, plasma
      cholesterol concentration, diastolic blood pressure, body mass index and self
      reported behaviours (smoking, exercise, alcohol intake, and diet) in comparison
      with internal and external control groups. RESULTS: Comparisons between the full
      health check and the internal control groups showed a small difference (0.13
      mmol/l) in the change in mean cholesterol concentration (95% confidence interval
      0.02 to 0.22, P = 0.02) but no significant differences for changes in Dundee risk
      score (P = 0.21), diastolic blood pressure (P = 0.71), body mass index (P =
      0.16), smoking (P = 1.00) or exercise (P = 0.41). Significant differences between
      the two groups were detected for changes in self-reported consumption of alcohol
      (41% in group with full health check v 17% in internal control group, P = 0.001)
      fruit and vegetables (24% v 12%, P < 0.001), and fat (30% v 9%, P < 0.001).
      Comparison of all groups showed no advantage from feedback of cholesterol
      concentration or risk score, or both. CONCLUSIONS: The health check only had a
      small effect on reversible coronary risk. It was effective in influencing self
      reported alcohol consumption and diet. Feedback on cholesterol concentration and
      on risk score did not provide additional motivation for a change in behaviour.

PMID- 8555807
TI  - Dermatology.

PMID- 8555808
TI  - Should doctors be more proactive as advocates for victims of violence?
AB  - Currently the management of adult victims of violence by general practitioners
      and accident and emergency departments is reactive, concerned almost exclusively
      with the management of physical injuries. Professor Jonathan Shepherd outlines
      some ideas for a more proactive approach on the part of doctors to improve the
      protection and support of vulnerable people; to deal with psychological sequelae;
      to take the responsibility of making an official complaint to the police away
      from seriously injured people, who are unable to give or withhold consent to
      disclosure; and to prevent assailants inflicting further injuries. We asked a
      sociologist, a psychiatrist, a moral philosopher, and a police surgeon for their
      comments.

PMID- 8555809
TI  - Clinical trials and rare diseases: a way out of a conundrum.
AB  - Currently, clinical trials tend to be individually funded and applicants must
      include a power calculation in their grant request. However, conventional levels
      of statistical precision are unlikely to be obtainable prospectively if the trial
      is required to evaluate treatment of a rare disease. This means that clinicians
      treating such diseases remain in ignorance and must form their judgments solely
      on the basis of (potentially biased) observational studies experience, and
      anecdote. Since some unbiased evidence is clearly better than none, this state of
      affairs should not continue. However, conventional (frequentist) confidence
      limits are unlikely to exclude a null result, even when treatments differ
      substantially. Bayesian methods utilise all available data to calculate
      probabilities that may be extrapolated directly to clinical practice. Funding
      bodies should therefore fund a repertoire of small trials, which need have no
      predetermined end, alongside standard larger studies.

PMID- 8555810
TI  - Guide to the Internet. Logging in, fetching files, reading news.
AB  - Aside from email and the world wide web, there are several other systems for
      distributing information on the Internet. Telnet is a system that allows you to
      log on to a remote computer from anywhere on the Internet and affords access to
      many useful biomedical sites on the Internet. File transfer protocol (FTP) is a
      method of transferring files from one computer to another over the Internet. It
      can be used to download files, including software, from numerous publiclly
      accessible "anonymous FTP archives" around the world. Such archives can be
      searched using a tool known as Archie. Network News is a system of electronic
      discussion groups covering almost every imaginable subject, including many areas
      of medicine and the biomedical sciences; MOOs are virtual environments that allow
      real time electronic conferencing and teaching over the Internet. It is difficult
      to predict the future of medicine on the Internet. However, the net opens up many
      possibilities not available through previous technologies. It is now up to
      medical practitioners to realise the Internet's full potential.

PMID- 8555811
TI  - ABC of atrial fibrillation. Drugs for atrial fibrillation.

PMID- 8555812
TI  - Scare over oral contraceptives. Effect on behaviour of women attending a family
      planning clinic.

PMID- 8555813
TI  - Scare over oral contraceptives. Effect on women in a general practice in Devon...

PMID- 8555814
TI  - Scare over oral contraceptives ... and south Wales.

PMID- 8555815
TI  - Scare over oral contraceptives. Doctors should take warning seriously.

PMID- 8555816
TI  - Scare over oral contraceptives. Main public health issue is failure to use
      contraception.

PMID- 8555817
TI  - Scare over oral contraceptives. New group will review evidence for effective care
      in family planning.

PMID- 8555818
TI  - Scare over oral contraceptives. If a woman has not had a thrombotic event in
      years of use she is unlikely to have one now.

PMID- 8555819
TI  - Scare over oral contraceptives. Committee's action has compromised continuing
      studies.

PMID- 8555820
TI  - Scare over oral contraceptives. Risk is highest during first months of use.

PMID- 8555821
TI  - Scare over oral contraceptives. Studies implicate only gestodene and desogestrel.

PMID- 8555823
TI  - Placebo effects. Psychological, sociological, and general practice research may
      elucidate effects.

PMID- 8555822
TI  - Scare over oral contraceptives. Committee's action will undermine further
      research and development.

PMID- 8555824
TI  - Scare over oral contraceptives. Was Committee on Safety of Medicines' advice
      arrived at lawfully?

PMID- 8555825
TI  - Placebo effects. Concept of placebo should be discarded.

PMID- 8555826
TI  - Deciding which selective serotonin reuptake inhibitor to prescribe.

PMID- 8555827
TI  - Placebo effects. Placebos used not to be used in studies.

PMID- 8555828
TI  - Treating mentally disordered prisoners. Mental Health Act Commission should visit
      prisons.

PMID- 8555829
TI  - Treating mentally disordered prisoners. Solution to treating prisoners in
      hospital is financial.

PMID- 8555830
TI  - Notification of tuberculosis is compatible with venereal diseases regulations.

PMID- 8555831
TI  - Transverse myelitis unlikely to be due to measles, mumps, and rubella vaccine.

PMID- 8555832
TI  - Problem based learning at medical school. Some people think it's thrilling...

PMID- 8555833
TI  - Problem based learning at medical school ... and has been introduced successfully
      in Manchester.

PMID- 8555834
TI  - Problem based learning at medical school ... but not all do.

PMID- 8555835
TI  - Problem based learning at medical school. Problem based learning has been used
      for years in general practice in London...

PMID- 8555836
TI  - Mobility after amputation of a lower limb.

PMID- 8555837
TI  - A living will is not euthanasia.

PMID- 8555838
TI  - Accident and emergency doctors lack proper training in trauma.

PMID- 8555839
TI  - Scientific and letter fraud in the Victorian era.

PMID- 8555840
TI  - Review of prescribed treatment for children with asthma. Weaknesses in methods
      and analysis limit conclusions.

PMID- 8555841
TI  - Review of prescribed treatment for children with asthma. More recent data suggest
      guidelines are being adhered to.

PMID- 8555842
TI  - Sensible drinking.

PMID- 8555843
TI  - Britain poised to extend storage of frozen embryos.

PMID- 8555844
TI  - Ombudsman plans to locate blame in complaints cases.

PMID- 8555845
TI  - US journals veto tobacco funded research.

PMID- 8555846
TI  - Gynaecologist acquitted in hysterectomy case.

PMID- 8555847
TI  - Researchers face patent race for breast cancer gene.

PMID- 8555848
TI  - Russia fights flu outbreak.

PMID- 8555849
TI  - A randomised prospective comparison of percutaneous endoscopic gastrostomy and
      nasogastric tube feeding after acute dysphagic stroke.
AB  - OBJECTIVE: To compare percutaneous endoscopic gastrostomy and nasogastric tube
      feeding after acute dysphagic stroke. DESIGN: Randomised prospective study of
      inpatients with acute stroke requiring enteral nutrition. SETTING: One university
      hospital (Nottingham) and one district general hospital (Derby). SUBJECTS: 30
      patients with persisting dysphagia at 14 days after acute stroke: 16 patients
      were randomised to gastrostomy tube feeding and 14 to nasogastric tube feeding.
      MAIN OUTCOME MEASURES: Six week mortality; amount of feed administered; change in
      nutritional state; treatment failure; and length of hospital stay. RESULTS:
      Mortality at 6 weeks was significantly lower in the gastrostomy group with two
      deaths (12%) compared with eight deaths (57%) in the nasogastric group (P <
      0.05). All gastrostomy fed patients (16) received the total prescribed feed
      whereas 10/14 (71%) of nasogastric patients lost at least one day's feed.
      Nasogastric patients received a significantly (P < 0.001) smaller proportion of
      their prescribed feed (78%; 95% confidence interval 63% to 94%) compared with the
      gastrostomy group (100%). Patients fed via a gastrostomy tube showed greater
      improvement in nutritional state, according to several different criteria at six
      weeks compared with the nasogastric group. In the gastrostomy group the mean
      albumin concentration increased from 27.1 g/l (24.5 g/l to 29.7 g/l) to 30.1 g/l
      (28.3 g/l to 31.9 g/l). In contrast, among the nasogastric group there was a
      reduction from 31.4 g/l (28.6 g/l to 34.2 g/l) to 22.3 g/l (20.7 g/l to 23.9 g/l)
      (P < 0.003). In addition, there were fewer treatment failures in the gastrostomy
      group (0/16 versus 3/14). Six patients from the gastrostomy group were discharged
      from hospital within six weeks of the procedure compared with none from the
      nasogastric group (P < 0.05). CONCLUSION: This study indicates that early
      gastrostomy tube feeding is greatly superior to nasogastric tube feeding and
      should be the nutritional treatment of choice for patients with acute dysphagic
      stroke.

PMID- 8555850
TI  - Prenatal and postnatal prevalence of Turner's syndrome: a registry study.
AB  - OBJECTIVE: To study prevalence of Turner's syndrome in Denmark and to assess
      validity of prenatal diagnosis. DESIGN: Study of data on prenatal and postnatal
      Turner's syndrome in Danish Cytogenetic Central Register. SUBJECTS: All
      registered Turner's syndrome karyotypes (100 prenatal cases and 215 postnatal
      cases) during 1970-93. MAIN OUTCOME MEASURES: Prevalence of Turner's syndrome
      karyotypes among prenatally tested fetuses and Turner's syndrome among liveborn
      infants. RESULTS: Among infant girls, prevalence of Turner's syndrome was
      32/100,000. Among female fetuses tested by amniocentesis, prevalence of Turner's
      syndrome karyotypes was 176/100,000 (relative risk of syndrome, 6.74 compared
      with prevalence among untested pregnancies). Among female fetuses tested by
      chorion villus sampling, prevalence of syndrome karyotypes was 392/100,000
      (relative risk, 16.8). We excluded prenatal tests referred because of results of
      ultrasound scanning: among fetuses tested by amniocentesis revised relative risk
      was 5.68, while revised relative risk among fetuses tested by chorion villus
      sampling was 13.3. For 29 fetuses with prenatal diagnosis of possible Turner's
      syndrome, pregnancy was allowed to continue and 24 children were live born.
      Thirteen of these children were karyotyped postnatally, and diagnosis of Turner's
      syndrome had to be revised for eight, seven being normal girls and one boy. This
      gives tentative predictive value of amniocentesis in diagnosing Turner's syndrome
      of between 21% and 67%. There was no significant relation between mother's age
      and risk of Turner's syndrome. CONCLUSIONS: Discrepancy between prenatal and
      postnatal prevalence of Turner's syndrome challenges specificity of prenatal
      examination in diagnosing Turner's syndrome.

PMID- 8555851
TI  - Serial homicide.

PMID- 8555852
TI  - Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the acceptability and efficacy of adding cognitive
      behaviour therapy to the medical care of patients presenting with the chronic
      fatigue syndrome. DESIGN: Randomised controlled trial with final assessment at 12
      months. SETTING: An infectious diseases outpatient clinic. SUBJECTS: 60
      consecutively referred patients meeting consensus criteria for the chronic
      fatigue syndrome. INTERVENTIONS: Medical care comprised assessment, advice, and
      follow up in general practice. Patients who received cognitive behaviour therapy
      were offered 16 individual weekly sessions in addition to their medical care.
      MAIN OUTCOME MEASURES: The proportions of patients (a) who achieved normal daily
      functioning (Karnofsky score 80 or more) and (b) who achieved a clinically
      significant improvement in functioning (change in Karnofsky score 10 points or
      more) by 12 months after randomisation. RESULTS: Only two eligible patients
      refused to participate. All randomised patients completed treatment. An intention
      to treat analysis showed that 73% (22/30) of recipients of cognitive behaviour
      therapy achieved a satisfactory outcome as compared with 27% (8/30) of patients
      who were given only medical care (difference 47 percentage points; 95% confidence
      interval 24 to 69). Similar differences were observed in subsidiary outcome
      measures. The improvement in disability among patients given cognitive behaviour
      therapy continued after completion of therapy. Illness beliefs and coping
      behaviour previously associated with a poor outcome changed more with cognitive
      behaviour therapy than with medical care alone. CONCLUSION: Adding cognitive
      behaviour therapy to the medical care of patients with the chronic fatigue
      syndrome is acceptable to patients and leads to a sustained reduction in
      functional impairment.

PMID- 8555853
TI  - Relation between plasma lactate and blood cyanide concentrations in acute cyanide
      poisoning.

PMID- 8555854
TI  - Assessment of urine analysis for the diagnosis of tuberculosis.

PMID- 8555855
TI  - Does home visiting prevent childhood injury? A systematic review of randomised
      controlled trials.
AB  - OBJECTIVE: To quantify the effectiveness of home visiting programmes in the
      prevention of child injury and child abuse. DESIGN: Systematic review of 11
      randomised controlled trials of home visiting programmes. Pooled odds ratios were
      estimated as an inverse variance weighted average of the study specific odds
      ratios. SETTING: Randomised trials that were available by April 1995. SUBJECTS:
      The trials comprised 3433 participants. RESULTS: Eight trials examined the
      effectiveness of home visiting in the prevention of childhood injury. The pooled
      odds ratio for the eight trials was 0.74 (95% confidence interval 0.60 to 0.92).
      Four studies examined the effect of home visiting on injury in the first year of
      life. The pooled odds ratio was 0.98 (0.62 to 1.53). Nine trials examined the
      effect of home visiting on the occurrence of suspected abuse, reported abuse, or
      out of home placement for child abuse. Because of the potential for bias in
      outcome reporting in these studies, pooled effect estimates were not calculated.
      CONCLUSIONS: Home visiting programmes have the potential to reduce significantly
      the rates of childhood injury. The problem of differential surveillance for child
      abuse between intervention and control groups precludes the use of reported abuse
      as a valid outcome measure in controlled trials of home visiting.

PMID- 8555856
TI  - The Internet's challenge to health care provision.

PMID- 8555857
TI  - Collecting data in general practice: need for standardisation.

PMID- 8555858
TI  - Continuing increase in respiratory symptoms and atopy in Aberdeen schoolchildren.

PMID- 8555859
TI  - Marginal costs and benefits.
AB  - Decision makers are interested in measuring the costs and benefits of various
      interventions, and sometimes they are presented with the average costs and
      benefits of alternative interventions and asked to compare these. Usually a newer
      intervention is being compared with an existing one, and the most appropriate
      comparison is not of average costs (and benefits) but of the extra--or marginal-
      costs (and benefits) of the new intervention. Reanalysis of the cost
      effectiveness ratio of biochemical screening of all women for Down's syndrome
      compared with age based screening shows that the marginal cost effectiveness of
      biochemical screening is 47,786 pounds, compared with an average cost
      effectiveness of 37,591 pounds. It may sometimes be difficult or costly to
      calculate marginal costs and benefits, but this should be done whenever possible.

PMID- 8555860
TI  - Nephrotic syndrome in childhood complicated by life threatening pulmonary oedema.

PMID- 8555861
TI  - Should backache be treated with spinal fusion? Spinal fusion is the only
      treatment for discogenic pain.

PMID- 8555862
TI  - Should backache be treated with spinal fusion? The case for spinal fusion is
      unproved.

PMID- 8555863
TI  - Virtual reality in rehabilitation.

PMID- 8555864
TI  - ABC of atrial fibrillation. Antithrombotic treatment for atrial fibrillation.
AB  - Antithrombotic prophylaxis with long term warfarin or aspirin reduces
      thromboembolic risk in atrial fibrillation. Identification, risk assessment, and
      regular review of all patients with atrial fibrillation should be routine in
      general and hospital practice. Risk stratification is easily performed on
      clinical grounds--echocardiography may refine it.

PMID- 8555865
TI  - Minimally invasive surgery for male subfertility.

PMID- 8555866
TI  - Quality of service provision for anticoagulation in atrial fibrillation. Bridges
      from evidence to practice are fragile.

PMID- 8555867
TI  - Quality of service provision for anticoagulation in atrial fibrillation. Many
      patients are ineligible.

PMID- 8555868
TI  - Quality of service provision for anticoagulation in atrial fibrillation. Patients
      and doctors play it safe.

PMID- 8555869
TI  - Quality of service provision for anticoagulation in atrial fibrillation.
      Cardioversion should be attempted.

PMID- 8555870
TI  - Quality of service provision for anticoagulation in atrial fibrillation.
      Difficulties of routine treatment are exaggerated.

PMID- 8555871
TI  - Quality of service provision for anticoagulation in atrial fibrillation. In
      Finland anticoagulant treatment is monitored by general practitioners.

PMID- 8555872
TI  - Telephone interpreting service is available.

PMID- 8555874
TI  - Cancer among airline cabin attendants. Interpretation of study minimises
      occupational hazards.

PMID- 8555873
TI  - Cancer among airline cabin attendants. Risk due to active and passive smoking
      should have been mentioned.

PMID- 8555875
TI  - Ethics committees. Information that can be given to researchers over the
      telephone needs to be clarified.

PMID- 8555876
TI  - Ethics committees. Separate criteria should be drawn up for questionnaire based
      epidemiological studies.

PMID- 8555877
TI  - Treatment for benign positional vertigo.

PMID- 8555878
TI  - Ethics committees. Communities' confidentiality should be maintained and
      community consent sought.

PMID- 8555879
TI  - Accessing the Internet is far from easy.

PMID- 8555880
TI  - Long term care in later life. A mixed economy of care is necessary.

PMID- 8555881
TI  - Long term care in later life. Best providers should win contracts irrespective of
      their ownership.

PMID- 8555882
TI  - "Probiotic" remedies are not what they seem.

PMID- 8555883
TI  - Deaths in police custody.

PMID- 8555884
TI  - Patients taking stable doses of morphine may drive.

PMID- 8555885
TI  - Patients with hydrocephalus should have regular eye checks.

PMID- 8555886
TI  - Torture and war. Medical associations should try to stop torture in Israel.

PMID- 8555887
TI  - Land mine injuries in Afghanistan.

PMID- 8555888
TI  - Torture and war. Abduction results in family, emotional, and legal problems.

PMID- 8555889
TI  - Use of performance indicators for general practice.

PMID- 8555890
TI  - Acyclovir in recurrent herpes labialis.

PMID- 8555892
TI  - New battle looms for France over health reforms.

PMID- 8555891
TI  - Alcohol--pushing the limits.

PMID- 8555893
TI  - Exanthem subitum (roseola infantum) misdiagnosed as measles or rubella
      [corrected].

PMID- 8555894
TI  - Intermittent catheterisation: simple, safe, and effective but underused.

PMID- 8555895
TI  - Insidiously evolving, occult drug interaction involving warfarin and amiodarone.

PMID- 8555896
TI  - Clinical system security: interim guidelines.

PMID- 8555897
TI  - ABC of atrial fibrillation. Cardioversion of atrial fibrillation.

PMID- 8555898
TI  - Job sharing at a children's hospital: evaluation by medical staff.
AB  - OBJECTIVE: To evaluate job sharing for registrars at Princess Margaret Hospital
      for Children, Perth, by seeking responses from members of the relevant medical
      teams. DESIGN: A questionnaire was sent to all 126 medical staff within the
      hospital (and three managers in medical administration) asking their views on job
      sharing for registrars. OUTCOME MEASURES: Whether job sharing should continue,
      who should do it, at what stage of training, and the effects on patient care.
      RESULTS: Among the 77 respondents (60%) there was broad support for the
      continuation of job sharing at the hospital: only 5 of 37 consultants and 2 of 19
      non-job sharing registrars rejected the idea (with a further 4 consultants
      uncertain). 43% Of the consultants who had worked with job sharing registrars
      thought continuity of care was adversely affected. CONCLUSION: The committee for
      physician training of the Royal Australasian College of Physicians emphasises
      that advanced training should be flexible, with a wide range of opportunities for
      individuals to plan an appropriate training programme in line with their personal
      goals. This study has shown that job sharing for registrars at Princess Margaret
      Hospital for Children allows this choice. Action on concerns over any adverse
      effects on patient care should resolve any persisting disquiet.

PMID- 8555899
TI  - Impact of specialised paediatric retrieval teams. A regionally based retrieval
      service is warranted.

PMID- 8555900
TI  - Impact of specialised paediatric retrieval teams. Comparison of teams is
      difficult.

PMID- 8555901
TI  - Impact of specialized paediatric retrieval teams. Criteria indicating
      physiological morbidity were too non-specific.

PMID- 8555902
TI  - Impact of specialised paediatric retrieval teams. London group's findings
      supported by study in Leeds.

PMID- 8555903
TI  - Impact of specialised paediatric retrieval teams. Intensive care provided by
      local hospitals should be improved.

PMID- 8555904
TI  - Impact of specialised paediatric retrieval teams. Transfers within hospitals can
      be as risky as those between hospitals.

PMID- 8555905
TI  - Impact of specialised paediatric retrieval teams. Children are still transferred
      by non-specialist teams.

PMID- 8555906
TI  - Guidelines for prescribing combined oral contraceptives.

PMID- 8555907
TI  - Monitoring children's growth. Abnormal growth should also be defined by the
      crossing of height centiles.

PMID- 8555908
TI  - Monitoring children's growth. Relation between height and weight centiles may be
      more useful.

PMID- 8555909
TI  - Safety of complementary medicines should be monitored.

PMID- 8555910
TI  - Extra costs for disabled people.

PMID- 8555911
TI  - Topical treatments for head lice. Several questions remain.

PMID- 8555912
TI  - Topical treatments for head lice. Review's weaknesses may undermine its
      conclusions.

PMID- 8555913
TI  - Training of overseas qualified doctors in Britain.

PMID- 8555914
TI  - Urban hypothermia. Many elderly people cannot keep warm in winter without
      financial hardship.

PMID- 8555915
TI  - Urban hypothermia. Number of excess deaths during winter is large.

PMID- 8555916
TI  - Prioritised ambulance call out may be necessary.

PMID- 8555917
TI  - Incidence of HIV infection decreases because of nature of epidemics.

PMID- 8555918
TI  - Misleading meta-analysis. "Fail safe N" is a useful mathematical measure of the
      stability of results.

PMID- 8555919
TI  - People's cultural beliefs should be respected.

PMID- 8555920
TI  - Raw milk cheeses and Salmonella.

PMID- 8555921
TI  - Third generation oral contraception and venous thromboembolism.

PMID- 8555922
TI  - Men's health.

PMID- 8555923
TI  - Contestability: a middle path for health care.

PMID- 8555924
TI  - Evidence based medicine: what it is and what it isn't.

PMID- 8555925
TI  - Doctors on hunger strike in Bombay.

PMID- 8555926
TI  - Australia changes confidentiality code.

PMID- 8555927
TI  - Consumer watch-dog criticises pharmacy staff.

PMID- 8555928
TI  - Research finds genetic link to personality trait.

PMID- 8555929
TI  - Older women ignorant of breast screening.

PMID- 8555930
TI  - India's consumer groups call for more rational prescribing.

PMID- 8555931
TI  - Dutch may relent over euthanasia prosecutions.

PMID- 8555932
TI  - Increased morbidity and mortality related to asthma among asthmatic patients who
      use major tranquillisers.
AB  - OBJECTIVE: To assess the potentially increased risk of death or near death from
      asthma in asthmatic patients with psychosis. DESIGN: Case-control study. SETTING:
      The computerised health databases of the Canadian province of Saskatchewan.
      SUBJECTS: 131 cases of death or near death from asthma identified within a cohort
      of asthmatic patients; 3930 matched non-cases. EXPOSURE AND OUTCOME MEASURES: The
      exposure of interest was the use of major tranquillisers in the period before an
      outcome event. Outcomes included death or near death from asthma. RESULTS: Crude
      analyses showed that asthmatic patients who had used major tranquillisers in the
      previous 12 months were at a 3.2 (95% confidence interval 1.4 to 7.5) times
      greater risk of death or near death from asthma than asthmatic patients who did
      not use major tranquillisers. Past users of major tranquillisers who had recently
      discontinued use were at a particularly high risk (relative risk 6.6; 2.5 to
      17.6). Adjustment for use of antiasthma drugs and other confounders abolished
      this excess risk. CONCLUSIONS: Asthmatic patients who use major tranquillisers
      seem to be at an increased risk of death or near death from asthma. Physicians
      treating asthmatic patients with a history of use of major tranquillisers should
      exercise greater caution with regard to management of such patients.

PMID- 8555933
TI  - Physical illness in psychiatric patients may be managed poorly.

PMID- 8555934
TI  - Asthmatic patients with psychosis need special care.

PMID- 8555935
TI  - Third generation oral contraceptives and risk of venous thromboembolic disorders:
      an international case-control study. Transnational Research Group on Oral
      Contraceptives and the Health of Young Women.
AB  - OBJECTIVE: To test whether use of combined oral contraceptives containing third
      generation progestogens is associated with altered risk of venous
      thromboembolism. DESIGN: Matched case-control study. SETTING: 10 centres in
      Germany and United Kingdom. SUBJECTS: Cases were 471 women aged 16-44 who had a
      venous thromboembolism. Controls were 1772 women (at least 3 controls per case)
      unaffected by venous thromboembolism who were matched with corresponding case for
      age and for hospital or community setting. MAIN OUTCOME MEASURES: Odds ratios
      derived with stratified analyses and unconditional logistic regression to adjust
      for potential confounding variables. RESULTS: Odds ratios (95% confidence
      intervals) for venous thromboembolism were: for any oral contraceptives versus no
      use, 4.0 (3.1 to 5.3); for second generation products (low dose ethinyl
      oestradiol, no gestodene or desogestrel) versus no use, 3.2 (2.3 to 4.3); for
      third generation products (low dose ethinyloestradiol, gestodene or desogestrel)
      versus no use, 4.8 (3.4 to 6.7); for third generation products versus second
      generation products, 1.5 (1.1 to 2.1); for products containing gestodene versus
      second generation products, 1.5 (1.0 to 2.2); and for products containing
      desogestrel versus second generation products, 1.5 (1.1 to 2.2). Probability of
      death due to venous thromboembolism for women using third generation products is
      about 20 per million users per year, for women using second generation products
      it is about 14 per million users per year, and for non-users it is five per
      million per year. CONCLUSIONS: Risk of venous thromboembolism was slightly
      increased in users of third generation oral contraceptives compared with users of
      second generation products.

PMID- 8555936
TI  - Third generation oral contraceptives and risk of myocardial infarction: an
      international case-control study. Transnational Research Group on Oral
      Contraceptives and the Health of Young Women.
AB  - OBJECTIVE: To test whether use of combined oral contraceptives containing third
      generation progestogens is associated with altered risk of myocardial infarction.
      DESIGN: Matched case-control study. SETTING: 16 centres in Austria, France,
      Germany, Switzerland, and the United Kingdom. SUBJECTS: Cases were 153 women aged
      16-44 with a myocardial infarction event. Controls were 498 women (at least 3
      controls per case) unaffected by myocardial infarction who were matched with
      their corresponding case for age and for hospital or community setting within
      four months of the index infarction. MAIN OUTCOME MEASURES: Odds ratios derived
      with stratified analyses and unconditional logistic regression to adjust for
      potential confounding variables. RESULTS: The estimated odds ratio for myocardial
      infarction of third compared with second generation oral contraceptives among all
      651 study subjects was 0.36 (95% confidence interval 0.1 to 1.2) (P = 0.11). The
      odds ratio for the United Kingdom and Germany alone was 0.45 (0.1 to 1.8) (P =
      0.26). Other odds ratios for the five countries were 3.1 (1.5 to 6.3) (P = 0.003)
      for use of second generation products v no current use and 1.1 (0.4 to 3.4) (P =
      0.9) for use of third generation products v no current use. Among the confounding
      variables the independent contribution of smoking (for which adjustment was made
      in the above estimates) proved to be important (10.1 (5.7 to 17.9), P < 0.001).
      CONCLUSION: An odds ratio of 0.45 with wide confidence intervals shows that third
      generation oral contraceptives compared with second generation products are
      associated with a reduced risk of myocardial infarction or with no difference.
      This finding from an interim analysis should be interpreted with extreme caution.
      However, the excess risk of venous thromboembolism associated with the use of
      third generation products may be balanced by the reduced risk of myocardial
      infarction associated with the same products.

PMID- 8555937
TI  - Large outbreak of Salmonella enterica serotype paratyphi B infection caused by a
      goats' milk cheese, France, 1993: a case finding and epidemiological study.
AB  - OBJECTIVE: To assess the magnitude of a nationwide outbreak of infection with
      Salmonella enterica serotype paratyphi B and identify the vehicle and source of
      infection. DESIGN: A case finding study of S paratyphi B infection between 15
      August and 30 November 1993; a pair matched case-control study; an environmental
      investigation at a processing plant that produced a raw goats' milk cheese
      incriminated in the outbreak; phage typing and genotyping of food and human S
      paratyphi B isolates. SETTING: France, 15 August to 30 November 1993. SUBJECTS:
      273 patients with S paratyphi B infection; 59 pairs of cases and controls matched
      for age, sex, and city of residence. MAIN OUTCOME MEASURES: Numbers of cases and
      incidence rates by region of residence and age; matched odds ratios for dairy
      food preferences. RESULTS: Among the 273 cases there was one death; 203 (78%)
      strains belonged to phage type 1 var 3. The incidence of infection was greatest
      in the region where goats' milk cheese is commonly produced. Comparison of cases
      and controls showed a 12-fold greater risk of illness (95% confidence interval
      1.6 to 92.3) from eating brand A unpasteurised goats' milk cheese. S paratyphi B
      isolates of phage type 1 var 3 were recovered from cheese A, goats' milk at the
      plant processing cheese A, and goats' milk supplied to the plant by a single
      farm. Genotypic IS 200 typing of food and human 1 var 3 phage type isolates
      showed a common IS 200 pattern. CONCLUSION: This outbreak emphasises the
      potential health hazards of widely distributed unpasteurised milk products in
      France and the need for their close bacterial monitoring.

PMID- 8555938
TI  - Ethnic differences in the outcome of serum screening for Down's syndrome.

PMID- 8555939
TI  - Genetics versus environment in inflammatory bowel disease: results of a British
      twin study.

PMID- 8555940
TI  - Vocational training for general practice in inner London. Is there a dearth? And
      if so what's to be done?
AB  - OBJECTIVE: To identify the nature and extent of any vocational training deficit
      within the London initiative zone and investigate the reasons. DESIGN: Collation
      of statistics and postal questionnaire surveys. SETTING: Thames regions inside
      and outside the London initiative zone. SUBJECTS: General practice registrars,
      trainers, principals from non-training practices, and vocational training course
      organisers. MAIN OUTCOME MEASURES: Trends in numbers of general practice
      registrars, proportions of trainers, views on current vocational training in
      inner London. RESULTS: Numbers of general practice registrars fell significantly
      between 1988 and 1993 within the London initiative zone and in England overall.
      The number of registrars within the zone fell by more than in the rest of the
      Thames regions, where the decline was not statistically significant. A lower
      proportion of principals were approved as trainers within the zone than in the
      rest of the Thames regions and England overall. In their responses to the survey
      (88% of inner London registrars responded and 81% of outer Thames registrars)
      registrars suggested that improving remuneration and personal safety would make
      training in London more attractive. Trainers and non-trainers (response rates 89%
      and 66% respectively) also suggested increasing remuneration for trainers
      together with more protected time for training. CONCLUSIONS: Less vocational
      training takes place within the London initiative zone than in the rest of the
      Thames regions and England overall, although there are discrepancies in official
      statistics. As well as specific recommendations for improving recruitment to
      vocational training in inner London, measures to tackle inner city deprivation
      should also remain high on the political agenda.

PMID- 8555941
TI  - Cladosporium carrionii and Hormoconis resinae (C. resinae): cell wall and melanin
      studies.
AB  - Two phaeoid strains of the fungus Cladosporium carrionii (SR3 from a xerophyte
      species and PP8201 from a patient), and one strain of Hormoconis resinae
      (Cladosporium resinae), isolated from oil-impregnated soil, were analyzed for
      their cell wall composition by colorimetric methods, X-ray diffraction, infrared
      spectroscopy, and solid-state 13C-nuclear magnetic resonance. Results suggested
      that the cell walls were composed mainly of hexoses (34%-47%) as beta-1,3-glucan
      (some galactose and mannose were also present) and melanin, chitin being absent.
      Electron microscopic observations suggested that melanin was found not only in
      the cell wall but also in intracellular bodies resembling melanosomes.

PMID- 8555942
TI  - Selective acylation of plasma membrane proteins of Mycoplasma mycoides subsp.
      mycoides SC, the contagious bovine pleuropneumonia agent.
AB  - The plasma membrane of Mycoplasma mycoides subsp. mycoides SC (strain KH3J)
      contains over 160 polypeptides with apparent molecular masses ranging from 14 to
      125 kDa and isoelectric point values (pIs) from 5 to 9. In vivo labeling with
      [14C]-fatty acids revealed about 35 acylated polypeptides including the two major
      components p42 and p65 and displaying pIs between 5.5 and 9.0, with a majority
      between 6.5 and 8. The amphiphilic nature of most of these acyl proteins was
      confirmed by Triton X-114 phase partitioning. Gas-liquid chromatography analyses
      showed that the order of preference for protein acylation was 16:0 > 18:2c >
      18:1c > 18:0 > 14:0, with 16:0 being the major O-ester-bound fatty acyl chain and
      18:2c the major N-linked chain. The presence of S-glycerylcysteine and a ratio of
      [O-ester-bound acyl chains + N-linked chains]/O-ester bound chains of
      approximately 1.2 in M. mycoides subsp. mycoides SC membrane proteins are
      consistent with a lipid modification similar to that occurring in lipoproteins of
      Gram-negative eubacteria that contain an N-terminal acyl S-glycerylcysteine.

PMID- 8555943
TI  - Use of peracetic acid as a disinfectant in a water-treatment plant: effect on the
      plasmid contents of Escherichia coli strains.
AB  - Total thermotolerant coliforms (TTC) and Escherichia coli strains were isolated
      from sewage from a treatment plant before and after peracetic acid (PAA)
      disinfection. The plasmid profiles of 120 E. coli strains were analyzed. Although
      PAA disinfection effectively reduced the number of TTC and E. coli strains, the
      percentage of E. coli strains containing plasmids was not statistically different
      among water samples. The sizes of the plasmids found ranged from < 3 kb to > 56
      kb, but plasmids of between 3 and 5 kb were encountered most frequently.

PMID- 8555944
TI  - Characterization of six highly mosquitocidal Bacillus thuringiensis strains that
      do not belong to H-14 serotype.
AB  - Four strains belonging to Bacillus thuringiensis serovars thompsoni,
      malaysiensis, canadensis, jegathesan and two auto-agglutinating B.t. strains were
      identified as being highly toxic to the mosquito larvae of the species Aedes
      aegypti, Anopheles stephensi, and Culex pipiens. Their larvicidal and hemolytic
      activities were determined and compared with those of strains known to be highly
      mosquitocidal and/or cytolytic from serovars of B.t. israelensis, morrisoni,
      darmstadiensis, medellin, kyushuensis, and fukuokaensis. The electrophoretic
      protein profiles of purified crystals and immunological relationships with B.t.i.
      polypeptides were studied. Five out of the six new strains showed the same
      larvicidal and hemolytic activities and the same crystal proteins and toxin genes
      as B.t.i. One strain, B.t. jegathesan 367, presented a novel pattern of
      larvicidal activity and a protein profile different from those of other strains.

PMID- 8555945
TI  - Tobacco: the road to litigation, 1995.

PMID- 8555946
TI  - Settling old questions, stimulating new ones.

PMID- 8555947
TI  - Inherent problems with meta-analysis.

PMID- 8555948
TI  - Meta-analysis of remedial interventions with drink/drive offenders: a useful
      clarification of what is and is not known.

PMID- 8555949
TI  - Meta-analysis helps to define the policy-relevance of drink driving research.

PMID- 8555950
TI  - Remediation can only give what it has, so do not ask too much.

PMID- 8555951
TI  - The need to standardize methodology.

PMID- 8555952
TI  - Potential consequences from possible changes to Nordic retail alcohol monopolies
      resulting from European Union membership.
AB  - This paper projects the consequences of modifying or eliminating the current
      national alcohol retail monopolies in Sweden, Norway and Finland as a possible
      result of those countries' membership in the European Union (EU). First, the
      authors project absolute alcohol consumption in each country based on different
      possible changes in alcohol price and availability. Then they predict the future
      levels of alcohol-related problems likely to result from increased per capita
      alcohol consumption (Sweden and Norway only). All of the scenarios examined in
      this paper are expected to lead to increases in per capita alcohol consumption.
      The smallest increase in consumption would result from a partial elimination of
      the current monopoly and a modest reduction in alcohol prices. In that case,
      projected per capita consumption in Sweden for inhabitants 15 years and older
      would rise from 6.3 to 9.3 litres; in Norway, from 4.7 to 6.7 litres; and in
      Finland, from 8.4 to 11.1 litres. The greatest projected increase in consumption
      would result from a complete elimination of the state monopolies such that all
      beer, wine and spirits were sold in food shops, grocery stores and gasoline
      stations, along with a substantial drop in alcohol prices as a result of private
      competition within each country and increased cross-border alcohol purchases.
      That scenario would result in projected per capita consumption of 12.7 litres in
      Sweden, 11.1 litres in Norway and 13.7 litres in Finland. The authors project
      that a 1-litre increase in consumption would result in a 9.5% increase in total
      alcohol-related mortality in Sweden and a 9.7% increase in Norway. Further,
      alcohol-related assaults would increase by 9% in Sweden and 9.6% in Norway. A 5
      litre increase in consumption would result in a 62% increase in alcohol-related
      mortality in Sweden and a 60% increase in Norway, and a 57% increase in alcohol
      involved assaults in both countries.

PMID- 8555953
TI  - Young teenagers and access to alcohol in a Swiss canton: evidence from
      observational testing and from a telephone survey.
AB  - In the first part of the study, the readiness of bartenders and waiters to serve
      alcoholic beverages to young teenagers was studied. The fieldwork was conducted
      in a random sample of bars and restaurants in Lausanne and in villages of the
      canton of Vaud, where 13-year-old and 15-year-old boys ordered either beer or
      pastis (an aniseed-flavoured aperitif). Results showed that alcoholic beverages
      were very accessible to 13-year-old and 15-year-old youths although the minimum
      legal age for purchasing and consuming beer is 16 years and for pastis is 18
      years: 81% of the test orders were served. An analysis of interaction of patterns
      between servers and clients suggested that time necessary to refuse orders may
      play an important role in explaining this result. In the second part of the
      study, knowledge and attitudes of owners and managers of bars, restaurants and
      different kinds of commercial outlet were studied in a telephone interview survey
      about the minimum legal age for purchasing and consuming alcoholic beverages.
      Only 17% of the respondents knew the correct minimum legal ages for purchasing
      and consuming alcoholic beverages.

PMID- 8555954
TI  - HIV prevalence and risk behaviour among intravenous drug users attending HIV
      counselling and testing centres in Paris.
AB  - This study was designed to analyse sexual and drug use behaviour, to determine
      whether increased awareness can lead to behaviour change, and to evaluate the
      association between HIV seropositivity and potential risk factors. A 4-month
      survey was carried out on 147 IVDUs attending three HIV counselling and testing
      centres, 98% of whom had been using heroin for an average of 7 years, 85% in
      association with other drugs. Two-thirds of injectors reported having used
      "safer" injecting practices in the previous year. Most of the IVDUs were
      heterosexual, and had had an average of three sexual partners in the previous
      year. More than half of them had had high risk partners. Condoms were used by
      only 25% of IVDUs, and were more likely to be used with seropositive partners
      (38% versus 12.7%, p = 0.02). Patients considering themselves to be well informed
      about HIV transmission shared syringes significantly less often, but had the same
      sexual behaviour patterns as other subjects. The HIV prevalence rate (8.2%) in
      our sample was not statistically related to any risk factor apart from drug use
      duration, the latter possibly reflecting a cumulative exposure to HIV risks.
      Since sexual risk appears to be a potential long-term hazard for IVDUs, it is
      important that more attention be paid to providing counselling to specifically
      address this issue.

PMID- 8555955
TI  - The role of needle exchanges in modifying sharing behaviour: cross-study
      comparisons 1989-1993.
AB  - In this paper the relationship between sharing behaviour and needle-exchange
      attendance is examined. Data from three studies of drug misuse carried out
      consecutively from 1989 to 1993 in the north-west of England are compared.
      Samples differed in their drug preferences. Analyses of sharing injecting
      equipment comparing exchange attenders and non-attenders revealed different
      patterns in each of the studies. Among opiate injectors no differences were
      observed in the proportions using others' injecting equipment, but attenders not
      in treatment were more likely to pass on their used equipment. This was
      attributed to uneven patterns of availability in the early days of exchange
      provision. Primary amphetamine users attending a needle exchange shared less than
      non-attenders, although overall levels of sharing were higher. Frequency of
      sharing was lowest in the third study of polydrug users but proportions sharing
      were similar to the opiate users. There was no effect of exchange attendance on
      sharing. Multiple logistic regressions identified other important predictors in
      these studies, e.g. treatment status, an injecting partner and injecting friends.
      Interpretations of the relationship between exchanges and sharing should take
      account of local availability of sterile equipment and the characteristics of
      exchange clientele.

PMID- 8555956
TI  - The consistency of family and peer influences on the development of substance use
      in adolescence.
AB  - Latent growth modeling (LGM) was used to analyse longitudinal data for adolescent
      substance use from five overlapping age cohorts (11, 12, 13, 14, and 15 years at
      first assessment) measured at four annual time points. An associative cohort
      sequential model was tested for alcohol, cigarette and marijuana use with a
      sample of 345 adolescents (11-18 years old) from an urban area in the Pacific
      Northwestern region of the United States. Hypotheses concerning the shape of the
      growth curve, the extent of individual differences in the common trajectory over
      time, and the influence of family cohesion, peer encouragement and gender on
      initial substance use and shape of the growth curve were tested. Results
      indicated similarities between alcohol, cigarette and marijuana initial use and
      development, with peer encouragement and family cohesion predictive of initial
      levels of use, and changes in peer encouragement influencing the developmental
      trajectories of the three substances. Females were higher than males in initial
      status and developed less rapidly in their use of the substances than did males.
      Findings are discussed in terms of the similarities and differences in the
      developmental trajectories of the three substances and the importance of family
      and peer influences on these trends.

PMID- 8555957
TI  - Construct validity of the dependence syndrome as measured by DSM-IV for different
      psychoactive substances.
AB  - The Diagnosis of Drug Dependence in the Official Psychiatric Nomenclatures (DSM
      III-R, DSM-IV, and ICD 10) are based on the Drug Dependence Syndrome construct.
      Although the validity and utility of the dependence syndrome has been widely
      documented for alcohol, the generalizability of the dependence syndrome to other
      psychoactive substances is still not clear. Thus, this article examines the
      construct validity of the drug dependence syndrome, as measured by diagnostic
      criteria for DSM-IV, using both internal consistency analyses and confirmatory
      factor analyses. Data were obtained from non-mutually exclusive groups of abusers
      for five drugs (alcohol, cocaine, marijuana, opioids, sedatives, stimulants)
      drawn from a pool of 521 subjects obtained from drug treatment, general
      psychiatric and community samples. As predicted by the theory, drug dependence
      items were found to be unidimensional and factorially distinct from measures of
      the consequences of substance abuse (e.g. legal problems) for all drug groups.
      Moreover, the drug dependence items yielded internally consistent scales that
      produced a distribution of scores reflecting a continuum from low to high
      severity of abuse for all drugs.

PMID- 8555958
TI  - Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled,
      double-blind trial.
AB  - Laboratory trials have demonstrated the efficacy of nicotine replacement in
      smoking cessation but absolute success rates are low. For many, nicotine gum is
      hard to use and transdermal nicotine is slow-acting and passive. A new, faster
      acting nicotine nasal spray (NNS) can provide easily self-administered relief
      from cigarette withdrawal. The NNS was tested for safety and efficacy in smoking
      cessation. Two hundred and fifty-five smokers were randomized to NNS or a
      piperine placebo. Drug use was limited to 8-32 doses/day for 6 months. Subjects
      were tested while smoking and at post-cessation daily (week 1) with follow-up at
      weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence
      analyses (CO < or = 8 ppm; no slips) showed that NNS significantly enhanced
      success rates over placebo overall (p < 0.001) and at all test intervals.
      Differences at key intervals between active and placebo were: 63% vs. 40% (day
      5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs.
      10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable.
      Cotinine measures showed that replacement of nicotine approximated 30% of smoking
      levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3
      weeks for strict abstinence. It is concluded NNS is safe, efficacious and a
      viable alternative treatment for smoking cessation.

PMID- 8555959
TI  - The need to preserve historical material.

PMID- 8555960
TI  - A profile of alcohol and drug misusers in an Arab community.

PMID- 8555961
TI  - Alternative oxidase from mango (Mangifera indica, L.) is differentially regulated
      during fruit ripening.
AB  - Alternative oxidase is a respiratory-chain component of higher plants and fungi
      that catalyzes cyanide-resistant oxygen consumption. The activity of a
      alternative oxidase has been detected during ripening in several climacteric
      fruit including mango (Mangifera indica L.). Synthetic oligonucleotides,
      corresponding to conserved regions of the Sauromatum guttatum and Arabidopsis
      thaliana nucleotide sequences, were used as primers for polymerase chain reaction
      to amplify genomic DNA extracted from mango leaves. The 623-bp fragment was found
      to encode an open reading frame of 207 amino acids showing high identity to the
      S. guttatum enzyme. Using this fragment to screen a ripe mango mesocarp cDNA
      library, one full-length cDNA clone, designated pAOMI.1, was obtained that
      contained an open reading frame encoding a polypeptide of 318 amino acids. The
      predicted amino-acid sequence exhibited 62, 64 and 68% identity to the S.
      guttatum, soybean, and A. thaliana enzymes respectively, indicating that this
      cDNA encodes a mango homologue of the alternative oxidase. Gel blot hybridization
      showed that pAOMI.1 is likely to be encoded by a single-copy gene. The 1.6 kb
      transcript was induced during mango fruit ripening although the transcript was
      clearly detectable in unripe and developing fruit. Antibodies raised against the
      S. guttatum enzyme recognized three bands of approximately 27, approximately 33
      and approximately 36 kDa from mitochondrial mango proteins. Two of the bands were
      detectable before ripening and increase in ripe fruit, the other band (27 kDa)
      was barely present in unripe fruit but accumulated during ripening. The clone
      pAOMI.1 was able to complement an Escherichia coli hemA mutant deficient in
      cytochrome-mediated aerobic respiration. This is the first report on the analysis
      of alternative oxidase at the molecular level during the ripening of a
      climacteric fruit.

PMID- 8555962
TI  - Analysis of the protein kinase activity of moss phytochrome expressed in
      fibroblast cell culture.
AB  - In the moss Ceratodon purpureus a phytochrome gene encodes a phytochrome type
      (PhyCer) which has a C-terminal domain homologous to the catalytic domain of
      eukaryotic protein kinases (PKs). PhyCer exhibits sequence conservation to
      serine/threonine as well to tyrosine kinases. Since PhyCer is expressed very
      weakly to moss cells, to investigate the proposed PK activity of PhyCer, we
      overexpressed PhyCer transiently in fibroblast cells. For this purpose we made a
      chimeric receptor, EC-R, which consists of the extracellular, the membrane
      spanning and the juxtamembrane domains of the human epidermal growth-factor
      receptor (EGF-R) linked to the PK catalytic domain of PhyCer (CerKin). The
      expression of EC-R in transiently transfected cells was confirmed with antibodies
      directed against the extracellular domain of EGF-R or against CerKin. Both EGF-R
      and EC-R were immunoprecipitated from lysates of overexpressing cells with
      antibodies against the extracellular domain of EGF-R. Phosphorylation experiments
      were performed with the immunoprecipitates and the phosphorylation products were
      subjected to phosphoamino acid analysis. Phosphorylation products specifically
      obtained with EC-R-transfected cells exhibit phosphorylation on serine and
      threonine residues. In EC-R transfected cells the endogenous EGF-R showed
      enhanced phosphorylation of serine and threonine residues compared to EGF-R
      immunoprecipitated from control cells. Although CerKin is closest to the
      catalytic domain of a protein tyrosine kinase from Dictyostelium discoideum, EC-R
      does not appear to phosphorylate tyrosine residues in vitro. From our data we
      conclude that PhyCer carries an active PK domain capable of phosphorylating
      serine and threonine residues.

PMID- 8555963
TI  - Wheat ribosome-inactivating proteins: seed and leaf forms with different
      specificities and cofactor requirements.
AB  - Distinct forms of ribosome-inactivating proteins were purified from wheat
      (Triticum aestivum L.) germ and leaves and termed tritin-S and tritin-L,
      respectively. These differ in size and charge and are antigenically unrelated.
      They are both RNA N-glycosidases which act on 26S rRNA in native yeast
      (Saccharomyces cerevisiae) ribosomes by the removal of A3024 located in a
      universally conserved sequence in domain VII which has previously been identified
      as the site of action of ricin A-chain. Tritin-S and tritin-L differ in both
      their ribosome substrate specificities and cofactor requirements. Tritin-S shows
      only barely detectable activity on ribosomes from the endosperm, its tissue of
      synthesis, whereas tritin-L is highly active on leaf ribosomes. Additionally,
      tritin-S is inactive on wheat germ, tobacco leaf and Escherichia coli ribosomes
      but active on rabbit reticulocyte and yeast ribosomes. Tritin-L is active on
      ribosomes from all of the above sources. Tritin-S, unlike tritin-L shows a marked
      requirement for ATP in its action.

PMID- 8555964
TI  - Is there a case for haemorheological screening in the haemocompatibility testing
      of materials?
AB  - Bio-interactions between a material and blood govern the compatibility of the
      material with the human body and, therefore, the single most important
      requirement for the blood interfacing implants/devices is haemocompatibility. The
      decisive events which control haemocompatibility occur at the molecular level and
      affect the various subphases of blood rheology. This effect on the already
      complex human blood rheology can be used to our advantage in the screening of
      blood-contacting materials. An attempt has been made in the present work to
      evaluate the haemocompatibility of materials based on changes in microrheological
      parameters of human blood. Samples of materials of equal surface area known to be
      haemocompatible (medical grade silicon, polyvinyl chloride from blood bags) and
      materials known to be extremely haemo-incompatible (pyrex glass, copper, cotton
      fabric, all commercial grade) were incubated at 37.4 degrees C in freshly drawn
      anticoagulated whole human blood, and changes in the haemorheological parameters
      (whole blood, plasma viscosity, intrinsic viscosity of red cells, platelet
      aggregation, albumin fibrinogen ratio) have been evaluated. The results of the
      study show that alterations in the haemorheological parameters are reliable
      indicators to the compatibility/incompatibility characteristics of well-known
      substances and that there is a case for haemorheological screening of
      biomaterials in the overall framework of haemocompatibility tests.

PMID- 8555965
TI  - Toxicity of particulate silicon carbide for macrophages, fibroblasts and
      osteoblast-like cells in vitro.
AB  - There is widespread interest in the use of interfacial layers in the preparation
      of diamond and diamond-like carbon (DLC) coatings. These DLC coatings deposited
      onto metal substrates with a silicon carbide (SiC) interfacial layer exhibit
      improved adhesion and show promise as wear-retardant coatings for biomedical
      implants. Although the DLC coatings show excellent biocompatibility in vitro,
      they may be susceptible to damage within the biological environment, leading to
      exposure of the interfacial silicon carbide. We have investigated the effects of
      two forms of silicon carbide (alpha-SiC and beta-SiC) on macrophages, fibroblasts
      and bone cells in vitro. Both alpha- and beta-SiC are well-tolerated by cells at
      concentrations of up to 0.1 mg/ml but cause severe cytotoxicity at a
      concentration of 1 mg/ml. If SiC is to be used as an interfacial layer on
      biomedical implants, the quality of the DLC coating must be optimised to minimise
      the risk of film breakdown.

PMID- 8555967
TI  - Thyroid diagnosis by thermogram sequence analysis.
AB  - A computerised thermal imaging system for thyroid diagnosis was developed by the
      authors and it was discovered that the rate of changes of temperature, rather
      than the absolute values, associated with a sequence of thermograms could help
      the medical doctors to identify clinical disorders. In order to further enhance
      the diagnostic capabilities and speed, a new method for medical thermogram
      analysis has been developed that compresses a sequence of thermograms into one
      thermogram while retaining the important information such as the geometrical
      patterns of the objects and the rate of temperature changes of each pixel within
      the images. As motion artifacts are unavoidable when a patient undergoes minutes
      of thermogram recording, direct comparison between images is deemed impossible. A
      high speed image matching algorithm has been developed to provide an absolute
      geometrical foundation for pixel-to-pixel comparison. The rate of change of
      temperature of a particular pixel along the sequence is represented by one single
      parameter after a process of temperature integration which can then be converted
      into a corresponding gray level for display. The resultant compressed thermogram
      can give a clear distinction between problem areas and normal ones. Although our
      emphasis is on thyroid diagnosis, it is anticipated that this new technique can
      be applicable to other areas of a human body.

PMID- 8555966
TI  - A study of the abrasive resistance of metal alloys with applications in dental
      prosthetic fixators.
AB  - Wear is one of the main surface failure mechanisms in materials and it will play
      a leading role in substitutive dental biomaterials. The aim of the present study
      is to compare the abrasive wear of different metallic materials used in dental
      applications. The results show that the abrasive wear of alloys based on precious
      metals such as Pt, Pd, Au and Ag is higher than for Ti and Ti based alloys. The
      alloy with the highest wear resistance is the Co-Cr which exhibits as well the
      highest hardness and Young's modulus. Since the method corresponds to a well
      established abrasive wear standard, the behaviour of the different materials can
      be easily compared.

PMID- 8555968
TI  - The use of Fourier transform infrared spectrometry for monitoring the retention
      of polymers in the vitreous humour.
AB  - A frequent cause of the failure of various materials tested as artificial
      vitreous substitutes is their short retention in the vitreous humour of the eye.
      Previous techniques to monitor the residence time of the vitreous substitutes
      have been traditionally complicated and usually involved the chemical
      modification of the test fluids. Fourier transform infrared (FTIR) spectrometry
      is used in this study to determine the rate of disappearance of a crosslinked
      poly(1-vinyl-2-pyrrolidinone) (PVP) hydrogel after injection into the vitreous
      humour of rabbits. The fluid removed from the eye at various postoperative
      intervals of time (1 day, 1 week, and 1 month) was placed on a horizontal
      attenuated reflectance (ATR) unit, and the infrared spectrum from 700 to 3000 cm
      1 was obtained directly. The absorption band at 1295 cm-1 due to C-N stretching
      vibration does not overlap with bands of any other species (natural vitreous,
      blood) present in the test fluid. By estimating the intensity of this band, it
      was found that about 80% of the injected polymer was removed from the vitreous
      cavity within 1 month. This study shows that (1) FTIR spectrometry is a
      convenient method to assess the residence time of foreign materials in the
      vitreous humour, and (2) the PVP gel is unsuitable in this current form as a
      permanent vitreous substitute, regardless of the pathways of its removal, such as
      phagocytosis of fragments produced by the injection process, or enzymatic
      biodegradation.

PMID- 8555969
TI  - Kinetic mechanism of the inhibition of human urinary kallikrein by basic
      pancreatic trypsin inhibitor.
AB  - Hydrolysis of D-valyl-L-leucyl-L-arginine p-nitroanilide (D-Val-Leu-Arg-Nan) at
      five different concentrations (10-20 microM) by human urinary kallikrein was
      studied in the absence and in the presence of increasing concentrations of basic
      pancreatic trypsin inhibitor (BPTI) (1.35-9.15 nM). The data indicate that the
      inhibition of human urinary kallikrein by BPTI is not a simple competitive
      inhibition as reported by others, but that it is a competitive inhibition of the
      parabolic type, with two inhibitor molecules binding to one enzyme molecule, with
      the formation of a ternary enzymatic complex. Statistical analysis of the
      experimental data supports the kinetic model proposed. The calculated values of
      the constants Ki and Kii were 16.20 nM and 1.10 nM, respectively. It is
      noteworthy that the Kii < Ki, i.e., the second BPTI molecule binds to the enzyme
      with a larger affinity suggesting that this second binding site was probably
      created or positively modulated as a consequence of the binding of the first BPTI
      molecule.

PMID- 8555970
TI  - Alcohol flushing, patch test, and ADH and ALDH genotypes in Brazilian ethnic
      groups.
AB  - Self reports of flushing reaction after drinking, cutaneous sensitivity to
      alcohol (patch test), and genotypic determination of ADH2, ADH3, and ALDH2 were
      studied in 53 Brazilian volunteers of different ethnic groups. Genotypes were
      determined using single-strand conformation polymorphism in discontinuous buffer
      electrophoresis. Analysis of the results indicated several cases of a reported
      flushing reaction among ALDH2 1/1 individuals, while all but 2 cases of ALDH2
      heterozygotes reported a flushing reaction. The latter subjects also had a
      negative result in the patch test. These preliminary results indicate that
      variability in the facial flushing reaction to alcohol seems to be a phenomenon
      resulting not only from the presence of a deficient ALDH2*2 allele, but also from
      other polymorphisms of alcohol-metabolizing enzymes.

PMID- 8555971
TI  - Preparation and characterization of dipalmitoylphosphatidylcholine liposomes
      containing interleukin-2.
AB  - Human recombinant interleukin-2 (IL-2) has been associated or mixed with small
      unilamellar vesicles prepared from dipalmitoylphosphatidylcholine (DPPC).
      Whatever the mode of IL-2 introduction, a considerable proportion of the added
      protein was associated with the liposomes, as determined by gel filtration and
      ultrafiltration/centrifugation, suggesting that IL-2 can interact with the lipid
      bilayer as well as being entrapped within the aqueous phase. Moreover, IL-2
      prevented the aggregation/fusion of the vesicles at 4 degrees C. Liposome
      associated protein was partially protected from digestion by pepsin, especially
      at the C-terminal, since no fluorescence emission from the tryptophan in this
      region was detected in the resulting peptides after separation by HPLC. Such
      systems could constitute a sustained release form of IL-2 for immunotherapy.

PMID- 8555972
TI  - Abnormalities in gallbladder dynamics of type 1 (insulin-dependent) diabetic
      patients with autonomic neuropathy.
AB  - The aim of this study was to evaluate gallbladder dynamics in insulin-dependent
      diabetic patients with and without autonomic neuropathy. Gallbladder dynamics was
      studied by a scintigraphic method after a test meal in 26 insulin-dependent
      diabetic patients and 10 normal individuals. The presence and severity of
      autonomic neuropathy were defined according to the number of abnormal
      cardiovascular reflex tests: absent (no abnormal test), mild (1-3 abnormal
      tests), and severe (4-5 abnormal tests). The time from the moment when the
      patient started to take the test meal to the beginning of gallbladder emptying
      was longer (P = 0.01) in diabetic patients with mild (N = 11, 12.1 +/- 7.6 min)
      and severe neuropathy (N = 8, 11.0 +/- 10.6 min) than diabetic patients without
      autonomic neuropathy (N = 7, 3.9 +/- 4.4 min) and controls (N = 10, 4.8 +/- 4.2
      min). The ejection rate was higher (P = 0.02) in the group with severe autonomic
      neuropathy (N = 8, 5.1 +/- 3.3%/min) than diabetic patients with mild (N = 11,
      2.0 +/- 1.0%/min) or without autonomic neuropathy (N = 7, 1.8 +/- 0.8%/min) and
      controls (N = 10, 2.6 +/- 1%/min). Thirty-two percent of the diabetic patients
      with autonomic neuropathy presented increased perspiration, nausea and urgency to
      defecate after the ingestion of the test meal. A significant positive correlation
      of ejection rate with the presence of these symptoms (biserial point correlation
      test = 0.67, P < 0.01) was also observed. These data suggest that insulin
      dependent diabetic patients with autonomic neuropathy present abnormalities of
      gallbladder emptying that could be related to specific gastrointestinal symptoms.

PMID- 8555973
TI  - Comparison of the determination of insulin by a monoclonal antibody-based
      immunofluorometric assay and by radioimmunoassay.
AB  - This paper describes an immunofluorometric assay (IFMA) for insulin and compares
      it with the classical radioimmunoassay (RIA). Monoclonal antibodies against
      insulin were produced and used to develop the IFMA. One, immobilized on
      microtiter plates, was used for capture, the other, labelled with Europium, was
      used as tracer antibody. The IFMA presents sensitivity to an amount of insulin of
      3 pmol/l and acceptable values for intra- and interassay error. The IFMA
      presented superimposable curves for human insulin, Arg65/Gly66-split proinsulin
      and des-Lys64,Arg65, and no cross-reactivity with human proinsulin, Arg32/Glu33
      split and des-Arg31,Arg32. The RIA showed 100% cross-reactivity with human
      proinsulin, 90% with Arg32/Glu33-split, 193% with Arg65/Gly66-split, 340% with
      des-Arg31,Arg32 and 170% with des-Lys64,Arg65. The assays were used to measure
      insulin in 300 serum samples from 50 subjects submitted to an oral glucose
      tolerance test (OGTT). Twenty were normal, 10 had impaired glucose tolerance and
      20 non-insulin-dependent diabetes mellitus. The mean value (+/- SEM) obtained by
      IFMA was 166.7 +/- 12.1 pmol/l and the mean value obtained by RIA was 339.6 +/-
      18.6, with a correlation of r = 0.80 (P < 0.01). Comparison of basal insulin
      levels of the different groups of individuals using IFMA or RIA led to the same
      conclusions. The area under the curve showed statistically significant
      differences only for the comparison between normal lean subjects and individuals
      with impaired glucose tolerance, when measured by RIA. Our data stress the
      importance of methodology definition when comparing insulin results.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8555974
TI  - Comparison of outer membrane protein and lipopolysaccharide profiles of
      enterotoxigenic Escherichia coli strains isolated in Sao Paulo, Brazil.
AB  - The outer membrane protein (OMP) and lipopolysaccharide (LPS) patterns of 12
      strains of serogroups of enterotoxigenic E. coli frequently isolated in Sao Paulo
      city were determined by fractionation techniques and by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). Five O6, three O78 and four O128
      serogroup isolates of different serotypes (flagellar antigens) and virulence
      factors (toxins and colonization factor antigens) showed a high degree of
      variability in their OMP pattern and at least nine groups could be identified.
      The analysis of LPS patterns by SDS-PAGE showed a homogeneous profile for the O6
      strains and some minor differences for the O128 and O78 strains. The present data
      indicate that analysis of OMP and LPS by SDS-PAGE may further improve the
      discriminating ability of extensively used serological techniques or the
      detection of virulence factors and could be a useful tool in epidemiological
      studies of enterotoxigenic E. coli (ETEC) strains from this area.

PMID- 8555976
TI  - The influence of social isolation and peripheral innervation on Ehrlich tumor
      growth in mice.
AB  - The relationship between social isolation and Ehrlich tumor growth was
      investigated in seven male NIH mice about 2 months old living separately in small
      cages for 28 days. Fifteen control animals were kept grouped in conventional
      cages (10 animals in one and 5 in another) for the same period. After this
      period, 40 to 50 microliters of a cell tumor suspension at a concentration of 1
      to 5 x 10(7) tumor cells/ml was inoculated into the footpad and footpad size was
      measured for 10 days. Isolated mice presented a 30% reduction in tumor growth.
      Sciatic and saphenous neurectomy in one leg of 5 isolated mice (experimental) and
      5 grouped mice (control) performed 7 days before tumor inoculation abolished this
      difference, and more tumor growth was observed in the neurectomized paw compared
      to the non-neurectomized paw. The subordinate x dominant social relationship
      established between mice living in groups of two per cage (seven cages) did not
      modify the growth of tumor inoculated under the same conditions compared to the
      first experiment. We conclude that social isolation and an intact peripheral
      innervation are associated with reduced tumor growth, but dominance behavior has
      no effect.

PMID- 8555975
TI  - Neutralization of the effect of Crotalus durissus terrificus venom by
      gangliosides.
AB  - We determined the ability of a mixture of gangliosides (16% GD1b, 19% GT1b, 21%
      GM1, 40% GD1a) to neutralize the effect of Crotalus durissus terrificus (Cdt)
      venom in vitro and in vivo. Protection was indicated by the absence of muscular
      contractions, hind limb paralysis or death of BALB/c mice (16-18 g) after
      receiving Cdt venom (1 microgram Cdt venom containing 0.6 microgram protein) at
      the doses indicated. A dose of Cdt venom above 0.9 microgram (ip) or 1 microgram
      (im) induced muscular contraction and above 1.2 micrograms (ip) or 5.5 micrograms
      (im) the venom induced muscular contraction and hind limb paralysis. Cdt venom
      above 2.5 micrograms (ip) or 9 micrograms (im) induced all these symptoms and 95
      to 100% death in experimental animals. The lethal dose 50% of the Cdt venom used
      was 8 micrograms (im) and 1.5 micrograms (ip). In in vitro studies, 4 mg
      gangliosides neutralized the effect of up to 1.5 micrograms Cdt venom. Quantities
      as low as 0.2 mg gangliosides were capable of neutralizing 0.9 microgram of Cdt
      venom in vitro. Intramuscular treatment with 1 mg gangliosides performed 60 min
      after the intramuscular injection of 5 micrograms Cdt venom protected 100% of the
      animals. In contrast, no protection was achieved with intraperitoneal treatment
      with gangliosides. The data show that gangliosides were effective in neutralizing
      the toxic effects induced by Crotalus durissus terrificus venom both in vitro and
      in vivo and that post-exposure intramuscular treatment with gangliosides could
      protect animals experimentally inoculated with the venom.

PMID- 8555977
TI  - Effect of zinc deficiency induced before and during pregnancy on the survival of
      female rats and their pups.
AB  - The objective of the present study was to determine the consequences of Zn2+
      deficiency on the gestational process. The study was conducted on adult Wistar
      virgin female rats fed isocaloric diets containing 16% protein and different Zn2+
      concentrations, i.e., 2 ppm (severe restriction), 6 ppm (moderate restriction),
      and 20 ppm (control). Rats received the diets and water ad libitum for 7, 14 or
      21 days before mating and throughout pregnancy. Survival of dams and pups
      decreased with increasing Zn2+ restriction and with time of exposure to the
      deficient diet. Mean survival rate for control dams and pups was 100%, whereas
      severe restriction (2 ppm for 21 days premating and during pregnancy) resulted in
      survival rates of 25% and 0 for dams and pups, respectively. Dam and pup survival
      rates for moderate restriction (6 ppm) for the same period were 83% and 72%,
      respectively. These results indicate the importance of Zn2+ before and during
      pregnancy and show that Zn2+ deficiency causes metabolic alterations which impair
      normal reproductive processes.

PMID- 8555979
TI  - Immune evasion by Trypanosomatidae: normal aggregated immunoglobulin protects
      against lysis by the alternative complement pathway.
AB  - Immunoglobulin Fc receptors (FcRs), present in Trypanosomatidae pathogenic for
      mammals, may be a mechanism by which these parasites escape the host immune
      response. We studied the possible role of these receptors in evasion by the
      alternative complement pathway. Promastigotes of Leishmania amazonensis and
      trypsinized trypomastigotes of Trypanosoma cruzi treated with heat-aggregated
      normal gamma globulin and then incubated with fresh normal guinea pig serum were
      shown to be more resistant to lysis. When compared to log phase Leishmania
      promastigotes, this resistance was at least 4.5-fold greater in parasites
      harvested in the stationary growth phase. EDTA and EGTA plus MgCl2 inhibited the
      cytotoxic effect of serum, suggesting the participation of the alternative
      complement pathway. The distribution of FcRs among genera of Trypanosomatidae
      that are pathogenic, infective or noninfective for mammals and their affinity for
      mammalian and fowl immunoglobulin were also examined. These receptors are present
      only in species infective or pathogenic for mammals, a finding that suggests that
      this structure is essential for the establishment of infection but is not
      necessarily a virulence factor. Furthermore, the ligand specificity is limited to
      the immunoglobulin of mammalian but not of fowl origin.

PMID- 8555978
TI  - Potent stimulation of murine B cells to proliferate and to secrete
      immunoglobulins by a lipoteichoic acid-like molecule produced by Clostridium
      botulinum C and D.
AB  - Bacterial products have served as important immunological tools to study
      lymphocyte activation. The lipopolysaccharides of the Gram-negative bacteria are
      well known to be potent activators of B lymphocytes. Several Gram-positive
      bacteria produce exotoxins that are superantigens for T cells. In the present
      study, we demonstrate that the Gram-positive bacteria Clostridium botulinum C and
      D produce a high molecular weight mitogen (Cb mitogen) that is a potent activator
      of murine B lymphocytes. The Cb mitogen was discovered as a consequence of our
      attempt to investigate a possible superantigen activity present in the botulinum
      exotoxins. We observed initially that mouse spleen cells were strongly stimulated
      to proliferate by culture supernatants of C. botulinum C and D. However, the
      characterization of the responding cell ruled out superantigen because only the B
      lymphocytes were stimulated to proliferate and to secrete immunoglobulins, and
      they did so independent of T cell help. In addition, the molecular
      characterization of the Cb mitogen demonstrated that the purified botulinum toxin
      was devoid of mitogenic activity. In contrast, the fractionation of the culture
      supernatant of C. botulinum C in an FPLC Superose 12 column indicated that the Cb
      mitogen was present in the void volume of the column (MW > or = 300 kDa) which
      had no toxigenic activity. However, the fractions containing molecules of 150 kDa
      were highly toxic for mice and had no mitogenic activity. The possibility that
      LPS was present as a contaminant in the Cb mitogen preparations was excluded
      because spleen cells from the LPS non-responder C3H/HeJ mice responded well to
      the Cb mitogen, and the antibiotic polymyxin B, which is an inhibitor of LPS, had
      no effect on the Cb-mitogen activity. However, an anti-lipoteichoic acid
      monoclonal antibody (3-1 mAb) inhibited to a great extent the proliferation of
      spleen cells induced by the Cb mitogen but had no effect on the LPS or
      concanavalin A stimulation of these cells. Moreover, the Cb mitogen was
      specifically adsorbed and eluted from a protein G Sepharose column to which the
      anti-lipoteichoic acid 3-1 mAb had been conjugated. These results support the
      view that lipoteichoic acid is a selective B cell mitogen.

PMID- 8555980
TI  - Behavior and progesterone levels in Callithrix jacchus females.
AB  - In callitrichids, and especially in the Callithrix and Saguinus genera,
      reproductive suppression maintains the breeding exclusivity of dominant females.
      It has been suggested that dominance may be inferred from agonistic behavior of
      females. The purpose of this study was to assess the adequacy of behaviors as
      indicators of hormonal status in Callithrix jacchus females. Two pairs of twin
      females were observed for affiliative, agonistic and sexual behaviors for 20
      weeks, in four stages of increasingly potential competition for one male. During
      the same period, blood samples were taken regularly for progesterone
      determination by ELISA. The two pairs differed markedly as to behaviors and
      hormonal status: pair 1 showed a well established behavioral dominance and only
      one ovulating female from the beginning of the observation period; pair 2 showed
      competition for dominance until the last stage of observation, when one of the
      females started ovulating. Correlations between behaviors and progesterone levels
      showed differences between subordinate and dominant females mostly in pair 2.
      Although limited in number of animals studied, these results suggest that there
      is a relationship between behavior and hormones in female marmosets, but this
      relationship may be useful in the identification of the physiological status of
      females only in groups where the dominance is not well established.

PMID- 8555981
TI  - Behavioral and pharmacological validation of the elevated plus maze constructed
      with transparent walls.
AB  - In this study we compared the performance of male Wistar rats, weighing 250-300
      g, submitted to the standard plus maze (vertical surfaces of the closed arms with
      opaque walls) to their performance in a modified maze with raised Plexiglas edges
      in the closed arms (transparent walls). The animals (N = 12 for each group)
      continued to show a clear preference for the closed arms with transparent walls
      of the modified elevated plus maze. In addition, exploratory activity was higher
      in the open arms of the modified plus maze (4.25 +/- 0.42 entries and 53.50 +/-
      5.10 s) as compared to that of the standard plus maze (2.10 +/- 0.25 entries and
      24.00 +/- 4.91 s). Intraperitoneal injection of midazolam produced an increase in
      the number of entries (6.40 +/- 1.21 and 8.50 +/- 1.15 for 1.0 and 2.0 mg/kg,
      respectively) and in the time spend in the open arms (85.32 +/- 14.56 and 125.50
      +/- 22.16 s for 1.0 and 2.0 mg/kg, respectively) while pentylenetetrazole caused
      a decrease in the number of entries (3.68 +/- 0.54 and 2.33 +/- 0.62 for 5.0 and
      10 mg/kg, respectively) and in the time spent in the open arms of the modified
      maze (39.60 +/- 6.67 and 23.60 +/- 6.40 s for 5.0 and 10 mg/kg, respectively).
      The anxiolytic effect of midazolam and the anxiogenic effect of
      pentylenetetrazole were similar to those usually reported in the literature by
      authors using the standard test. These results behaviorally and pharmacologically
      validate the elevated plus maze with transparent walls and suggest that this test
      could be a useful tool for the study of anxiolytic drugs and the neurobiology of
      anxiety.

PMID- 8555982
TI  - Changes in blood pressure control in aged rats.
AB  - The aging process is related to several changes in cardiovascular, metabolic and
      autonomic functions. However, descriptions of changes in arterial pressure (AP),
      baroreflex sensitivity and associated variations of serum glucose and insulin are
      controversial. The aim of this paper was to study AP, baroreflex sensitivity and
      changes in plasma levels of glucose and insulin of young (10 weeks, 239 +/- 4.3
      g) and aged (18-24 months, 412 +/- 8.5 g) male Wistar rats. AP pulses were
      videotaped and processed on a microcomputer, using an analog-to-digital converter
      (beat-to-beat analysis). Baroreflex sensitivity was evaluated measuring heart
      rate changes induced by mean arterial pressure (MAP) variations produced by
      phenylephrine and sodium nitroprusside injections (N = 10 in each group). Plasma
      glucose (N = 10 in each group) and plasma insulin (N = 6 in each group) were
      quantified by a colorimetric enzymatic test and radioimmunoassay, respectively.
      There were no differences in systolic, diastolic or mean AP (110 +/- 5 vs 107 +/-
      3 mmHg) between aged and young rats. The tachycardic response to the reduction of
      AP was impaired in aged compared to young rats (-1.95 +/- 0.29 vs -3.26 +/- 0.49
      bpm/mmHg), while the bradycardic response to increases in AP was similar (-1.02
      +/- 0.22 vs -1.5 +/- 0.26 bpm/mmHg). Basal levels of glucose (83 +/- 6 vs 62 +/-
      4 mg/dl) and insulin (8.3 +/- 2 vs 4 +/- 0.5 microU/ml) were different. Thus, the
      reflex tachycardia evoked by a fall in AP is depressed in old rats.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8555983
TI  - Atrial natriuretic peptide modulates the effect of angiotensin II on the
      concentration of free calcium in the cytosol of Mandin-Darby canine kidney cells.
AB  - The effect of angiotensin II (ANG II) and atrial natriuretic peptide (ANP) on
      intracellular free calcium concentration [Ca2+]i was investigated in Mandin-Darby
      canine kidney (MDCK) cells in culture. Changes in [Ca2+]i were monitored
      fluorometrically with the Ca(2+)-sensitive probe fura-2/AM at 37 degrees C using
      a Perkin-Elmer LS-5 spectrofluorimeter (excitation 340/380 nm, slit 3 nm;
      emission 520 nm, slit 10 nm). MDCK cells exhibited a mean baseline [Ca2+]i of 98
      +/- 10 nM. The addition of increasing concentrations of ANG II (1 pM to 1 microM)
      to the cell suspension led to a progressive increase in [Ca2+]i to 2-3 times
      basal levels. In contrast, addition of 1 microM ANP to the cell suspension led to
      a very rapid 60% decrease in [Ca2+]i. The addition of 1 pM to 1 microM ANG II
      immediately after 1 microM ANP caused an increase in [Ca2+]i which never exceeded
      the basal level in the absence of ANP. The data indicate that ANG II increases
      cell [Ca2+]i, as expected, and provide the new observation that ANP reduces
      [Ca2+]i in these cells. Furthermore, ANP reduces the increase in [Ca2+]i elicited
      by ANG II, thus modulating the effect of ANG II on [Ca2+]i.

PMID- 8555984
TI  - Functional organization of tau proteins during neuronal differentiation and
      development.
AB  - Tau proteins play major regulatory roles in the organization and integrity of the
      cytoskeletal network. In neurons, a specific axonal compartmentalization of tau
      has been shown. However, recent studies demonstrate that tau displays a
      widespread distribution in a variety of non-neuronal cell types. These proteins
      have been found in human fibroblasts and in several transformed cell lines. The
      heterogeneous family of tau is formed by a set of molecular species that share
      common peptide sequences. There is a single gene that contains several exons
      encoding for the six different tau isoforms in mammalian brain. Alternative
      splicing of a common RNA transcript as well as post-translational modifications
      contribute to its heterogeneity. Tau isoforms generated by splicing differ from
      one another by having either three or four repeats in their C-terminal half, and
      a variable number of inserts in their N-terminal moiety. These repeats have been
      shown to constitute microtubule-binding motifs. In this review some relevant
      aspects of tau function and its regulation are analyzed. Three major topics are
      discussed. The first one focuses on the tau roles in regulating the interactions
      between microtubules with actin filaments and with intermediate filament systems.
      Another problem deals with the question of whether tau isoforms segregate into
      functionally different subsets of microtubules in axonal processes, or tau
      associates with these polymers in a random fashion. The third question that
      emerges is the involvement of tau and tau-like proteins in morphogenetic events.
      The regulation of the interactions of DMAP-85, a recently discovered tau-like
      protein, with the cytoskeleton during development of Drosophila melanogaster is
      analyzed.

PMID- 8555985
TI  - New vaccines against tuberculosis.
AB  - It has proved difficult to vaccinate effectively against tuberculosis with
      mycobacterial components or even with whole dead mycobacteria; protection was
      always inferior to that obtained with the live attenuated vaccine known as
      bacillus Calmette-Guerin (BCG). We have found that this may no longer be the
      case. Expression of the gene for a single mycobacterial antigen (Mycobacterium
      leprae hsp65) in adult BALB/c mice resulted in substantial cell-mediated
      protection against challenge with M. tuberculosis, but only when it was generated
      as an endogenous antigen within antigen-presenting cells. CD4 and CD8 T cells
      cloned from spleens of immunized mice passively transferred protection to non
      immunized mice, and CD8 cells selectively lysed macrophages infected with M.
      tuberculosis. The ability of the clones to protect recipient mice against
      challenge infection was most strongly associated with specific cytotoxic capacity
      and secondarily with IFN-gamma production. Three modes of expressing the gene
      have been tested: a) expression from a retroviral vector (pZIPNeoSV) in implanted
      J774 tumor cells, b) expression from the same vector via bone marrow cells
      transfected in vitro and used to reconstitute irradiated mice, and c) in a
      preliminary experiment, from cytomegalovirus (CMV) immediate-early and
      hydroxymethylglutaryl Co-A reductase promoters injected as plasmid DNA into
      muscle.

PMID- 8555986
TI  - Decreased biological activity is related to abnormal multimeric structure of von
      Willebrand factor in pulmonary hypertension.
AB  - We evaluated the correlation between decreased biological activity and
      abnormalities in the multimeric structure of plasma von Willebrand factor (vWF)
      in 27 pulmonary hypertensive patients (median age, 21 years). The biological
      activity of vWF was measured by the ristocetin cofactor assay and its multimeric
      structure was assessed by Western immunoblotting after SDS-agarose gel
      electrophoresis. In spite of high antigenic activity of vWF in plasma (139 +/- 65
      vs 91 +/- 27% in controls, P = 0.003), the biological activity expressed as a
      percent of the control value was decreased in pulmonary hypertensive patients (60
      88% activity, 95% CI for the mean). High molecular weight multimers (biologically
      active forms) were absent in patients and there was a significant increase in the
      concentration of low molecular weight polymers in comparison with normals (56 +/-
      12 and 35 +/- 12% of total multimer density, respectively, P < 0.001). Multimeric
      abnormalities were positively correlated with plasma vWF levels (r = 0.51, P =
      0.007) and negatively correlated with vWF biological activity (r = -0.54, P =
      0.004). Thus, decreased biological function is related to abnormalities in the
      multimeric structure of vWF, possibly reflecting extensive endothelial
      dysfunction in pulmonary hypertension.

PMID- 8555987
TI  - Effects of almitrine on the ventilatory control, breathing pattern and maximal
      exercise tolerance in hypoxemic patients with chronic obstructive pulmonary
      disease.
AB  - Almitrine bismesylate improves arterial blood gases in patients with chronic
      obstructive pulmonary disease (COPD), but side effects such as increase of
      ventilatory drive and dyspnea have been reported in some studies. We studied 18
      COPD patients (mean age = 59.1 years; mean FEV1 = 0.92 1; mean PaO2 = 58.6 mmHg)
      in a double-blind randomized study using placebo or almitrine 50 mg twice a day
      by mouth, for 60 days. In contrast to the placebo group, 40% of the patients in
      the almitrine group presented a significant increase in PaO2 and a decrease in
      P(A-a)O2 > or = 5 mmHg during submaximal exercise after 60 days of treatment.
      Ventilatory drive and the breathing pattern were measured at rest and during
      submaximal exercise. Both groups showed high levels of ventilatory drive and a
      tachypneic breathing pattern before drug treatment and no modification was found
      30 and 60 days after treatment. Metabolic, cardiovascular and ventilatory
      variables were studied during an incremental to maximum exercise symptom-limited
      test (cycloergometry). Maximal VO2 ranged from 46 to 52% and heart rate from 76
      to 78% in relation to the predicted values. The percent ratio of ventilation at
      maximal exercise to maximal voluntary ventilation at rest ranged from 86 to 94%.
      These results show that the reduction of ventilatory capacity was the main factor
      decreasing the aerobic performance of our COPD patients. Maximal exercise
      tolerance (VO2 max) did not change after almitrine treatment. Negative factors
      like an increase in neuromuscular drive did not occur, and positive factors like
      an increase in PaO2 and oxygen transport had no critical influence on exercise
      performance in our ventilatory-limited COPD patients.

PMID- 8555988
TI  - Enteroviruses as a possible cause of myocarditis, pericarditis and dilated
      cardiomyopathy in Belem, Brazil.
AB  - We attempted to assess the role of enteroviruses in the etiology of myocarditis
      (MC), pericarditis (PC) and dilated cardiomyopathy (DCM) among 15 in-patients at
      a public hospital in Belem, Brazil, from November 1992 to December 1993. We
      obtained stool specimens and throat swabs from each patient (particularly acute
      cases) and, when possible, acute and convalescent serum samples for both
      isolation and serological procedures. MC, PC and DCM occurred in 10, 2 and 3
      patients, respectively, mostly in the 0- to 10-year age group. Neutralizing
      antibody seroconversions were detected as follows: one for Coxsackievirus (Cox)
      B2 in one patient suffering from MC, and two for Cox B4, in patients with DCM and
      MC. In addition, antibody titers of 1/320 against Cox B2 and Cox B4 were noted in
      two other patients, one suffering from PC and the other presenting MC. Isolation
      of echovirus (ECHO) serotype 1 was recorded in a patient with MC, without either
      seroconversion or high antibody levels for Cox B 1 to 6. These results indicate
      that enteroviruses may be involved in the etiology of MC, PC and DCM in the
      Amazon region.

PMID- 8555989
TI  - Theophylline-ranitidine interaction in elderly COPD patients.
AB  - Most controlled studies in humans indicate that ranitidine does not alter
      theophylline metabolism, even at high doses. However, there have been several
      case reports published recently which demonstrate the development of theophylline
      toxicity mostly in older patients receiving stable oral doses of this drug when
      ranitidine was administered simultaneously. We studied eleven elderly (mean age,
      69.0 +/- 6.2 years) patients with chronic obstructive pulmonary disease (COPD).
      During one week the patients took slow-release theophylline, 200 mg every 12 h,
      followed by one week intake of the same dose of theophylline plus ranitidine
      tablets, 150 mg every 12 h. At the end of each period, blood samples were
      obtained 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12 h after the morning dose for the
      determination of serum theophylline levels. The peak theophylline concentration
      (Tmax) was achieved after 4.1 +/- 0.9 h while the patients were taking
      theophylline, and after 2.9 +/- 1.4 h with the combined regimen. This difference
      was statistically significant (P < 0.01). In only 3/11 subjects did Tmax remain
      unchanged during both phases of the study. The mean theophylline clearance rates
      while the patients were receiving theophylline alone (39.58 +/- 19.89 ml/min) and
      when they were receiving both medications (34.42 +/- 10.55 ml/min) were similar.
      The mean serum levels while the patients were receiving theophylline alone were
      slightly higher but not statistically different. These results suggest that the
      reported increases in serum theophylline levels in older patients receiving
      theophylline and ranitidine cannot be ascribed to slower theophylline metabolism
      in the geriatric patients with COPD who is also given ranitidine.

PMID- 8555990
TI  - Effect of chronic estradiol administration on the acute pressor response to
      aortic coarctation in conscious rats.
AB  - We investigated the effect of chronic estradiol administration on the pressor
      response elicited by acute (45 min) partial aortic constriction in conscious
      Wistar rats and on vascular reactivity to angiotensin II and vasopressin in
      vitro. Estradiol (10 micrograms kg-1 day-1, sc) or vehicle was administered for 7
      days to young castrated male and female rats and to female rats that had stopped
      cycling (14-16 months of age). In the acute experiment of aortic coarctation in
      conscious rats, carotid pressure was monitored continuously before and for 45 min
      after partial abdominal aortic coarctation. In ovariectomized females the mean
      carotid pressure and heart rate before aortic coarctation were significantly
      lower in estradiol-treated animals (107 +/- 3 vs 119 +/- 3 mmHg and 360 +/- 31 vs
      494 +/- 12 bpm). Estradiol did not affect the pressor response (145-150 mmHg) to
      aortic coarctation of castrated male rats or ovariectomized female rats but
      blunted the reflex bradycardia of ovariectomized rats. The onset of the pressor
      response to aortic coarctation was delayed in aged female rats as compared to the
      other groups. While estradiol treatment significantly accelerated the onset of
      hypertension in aged rats, it did not affect the pressor response of castrated
      animals. Full dose-response curves to angiotensin II and vasopressin were
      constructed in vitro in the isolated mesenteric arterial bed obtained from
      similarly treated groups. Estradiol did not affect the vasopressin sensitivity or
      responsiveness of any group, but caused a significant increase in angiotensin II
      sensitivity in ovariectomized rats only.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8555991
TI  - Effect of high-salt intake on blood pressure and vascular reactivity of diabetic
      rats.
AB  - The etiopathogenesis of diabetes mellitus (DM)-associated hypertension is not
      known. Sodium and an increased vascular reactivity to vasopressor agents have
      been implicated in the pathogenesis of this disease in humans. The aim of the
      present study was to experimentally evaluate the possible role of salt intake and
      changes in vascular reactivity in the pathogenesis of DM-associated hypertension.
      Male Wistar rats, weighing 180 to 200 g, rendered diabetic by streptozotocin (65
      mg/kg) and maintained moderately hyperglycemic with insulin were submitted to
      high-salt intake (tap water replaced with 1.0% NaCl) for 8 weeks (D+salt rats, N
      = 8). Mean arterial pressure and reactivity of the isolated aorta to
      norepinephrine and angiotensin II were then determined. Diabetic rats on normal
      salt intake (group D+nl, N = 6) or normal-salt intake (group non-D+nl, N = 8)
      were used as controls. Mean blood pressure was significantly higher in D+salt
      rats (123 +/- 3 mmHg) compared with the D+nl (113 +/- 3 mmHg), non-D+salt (111 +/
      2 mmHg) and non-D+nl (105 +/- 2 mmHg) groups. Mean blood pressure was also
      significantly higher in diabetic rats on normal-salt intake compared with control
      rats on normal-salt intake. Vascular reactivity of the aorta to norepinephrine
      was increased only in diabetic rats on high-salt intake. No modification in
      reactivity was detected with regard to the reactivity to angiotensin II. We
      conclude that high-salt intake increases blood pressure in diabetic rats and that
      increased aorta vascular reactivity to norepinephrine might be involved in the
      blood pressure alteration.

PMID- 8555992
TI  - The mast cell revisited.
AB  - The role of mast cells in allergic reactions is reviewed and the origin,
      distribution and properties of mast cells are reported. The characteristics of
      two phenotypically distinct mast cell populations are described. The function and
      properties of the IgE molecule as an antigen receptor on mast cells is discussed.
      The IgE receptor and its structure is updated. The participation of mast cells in
      the acute and late phase of the allergic reaction is pointed out. A double role
      for mast cells in allergic reactions is suggested: they may be responsible for
      the acute phase reaction through the release of mediators such as histamine and
      leukotrienes and for the late phase reaction through the release of pro
      inflammatory cytokines.

PMID- 8555993
TI  - MHC class I-selected CD4-CD8-TCR alpha beta+ T cells: an important source of IL
      4.
AB  - Differentiation of naive CD4+ lymphocytes into either Th1 or Th2 cells is
      influenced by the cytokine present during initial antigen priming. IL-4 is the
      critical element in the induction of Th2 response; however, its origin during a
      primary immune response is not well-defined. Here, a novel source of IL-4, the
      class I-selected CD4-CD8-TCR alpha beta+ T cells, potentially implicated in the
      development of specific Th2 immune cells, is reviewed.

PMID- 8555994
TI  - The thymic nurse cell complex: an in vitro model for extracellular matrix
      mediated intrathymic T cell migration.
AB  - The thymus is a primary lymphoid organ in which bone marrow-derived T cell
      precursors undergo a complex maturation process in the context of the thymic
      microenvironment, represented by non-lymphoid cells and extracellular matrix
      (ECM) components. The thymic epithelial cells are the major cellular component of
      the thymic microenvironment, and influence different aspects of thymocyte
      differentiation, via cell-cell interactions and secretions of soluble factors,
      such as thymic hormones. The thymic nurse cell (TNC) complexes are multicellular
      lymphoepithelial structures formed by one thymic epithelial cell harboring 2-200
      thymocytes, primarily bearing the CD4/CD8 double-positive phenotype. TNCs
      probably create a special microenvironment for thymocyte differentiation and/or
      proliferation, with thymocytes being exposed to major histocompatibility complex
      (MHC) antigens and thymic hormones. Such differentiation parallels cell migration
      into and out of the complex. We showed the expression of ECM components and
      respective receptors by TNCs, and that interactions between the epithelial
      component of TNC and TNC-lymphocytes can be modulated by ECM components and
      respective receptors. Moreover, we demonstrated that intrinsic as well as
      extrinsic biological circuits can be involved in the control of such ECM-mediated
      thymic epithelial cell (TEC)/thymocyte interactions. For example, interferon
      gamma can biphasically modulate the expression of ECM ligands and receptors by
      TEC, which results in corresponding modulation of their ability to interact with
      TNC-thymocytes. Additionally, hormones such as triiodothyronine, prolactin and
      growth hormone can influence the degree of these lymphocyte/epithelial cell
      adhesive interactions. Lastly, we recently furnished evidence for a de-adhesive
      mechanism within TNC apparently mediated by galectin 3 (an endogenous soluble
      beta-galactoside-binding lectin).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8555995
TI  - Apoptosis as a cause of T-cell unresponsiveness in experimental Chagas' disease.
AB  - A murine model of Chagas' disease induced by metacyclic forms of T. cruzi was
      used to evaluate T-cell function during infection. T-cell unresponsiveness to
      TcR;CD3 stimulation in vitro and lymphocyte activation in vivo occurred
      simultaneously. These paradoxical findings are discussed in the light of recent
      evidence that mature activated T cells become susceptible to TcR-mediated
      apoptosis. Activation-induced death in T cells from T. cruzi-infected mice has
      recently been demonstrated in this model. Evidence that TcR-induced death of
      activated T cells could be a cause for T-cell unresponsiveness in vitro and in
      vivo, as well as the possible molecular mechanisms involved, are discussed.

PMID- 8555996
TI  - Immunochemical characterization of carbohydrate antigens from fungi, protozoa and
      mammals by monoclonal antibodies directed to glycan epitopes.
AB  - Cell surface carbohydrates constitute the major antigenic determinants of fungi
      and protozoa. Glycoconjugates also represent a large variety of antigens or
      markers present in mammals such as histo-blood groups ABO, differentiation and
      heterophile antigens, among others. This article focuses on the general
      properties of glycoconjugate antigens and production and characterization of the
      anti-carbohydrate monoclonal antibodies (MoAbs). It describes the specificity and
      some properties of monoclonal antibodies directed against carbohydrate epitopes
      present in tumor-associated glycoproteins, in glycosaminoglycans of higher
      eukaryotes and in glycolipid antigens of protozoa and fungi. The epitopes
      recognized by the anti-carbohydrate MoAbs range from one sugar unit up to ten
      sugar units. Although most anti-carbohydrate MoAbs are directed predominantly
      toward terminal sugar residues, a few MoAbs are also reactive with internal sugar
      residues. The fine structure of the carbohydrate epitopes has been chemically
      defined by [1H] NMR, GC/MS of alditol acetates of partially permethylated
      compounds, -FAB/MS, degradation with exoglycosidases and inhibition with
      different methyl-glycosides and oligosaccharides.

PMID- 8555997
TI  - The contribution of animal models to the understanding of the pathogenesis of
      type 1 diabetes.
AB  - The autoimmune nature of insulin-dependent diabetes mellitus (type 1 diabetes)
      has been definitively established during the past ten years only, owing
      essentially to the development of the NOD and the BB rat models. Three of the
      four criterias required for defining an autoimmune disease have been demonstrated
      in these animal models. IDDM is accompanied by immunological stigmatas including
      circulating autoantibodies and insulitis (lymphocytic infiltration of the islets
      of Langerhans), it is attenuated or prevented by immunosuppressors and it is
      transferable from diabetic to non-diabetic mice or rats, via T lymphocytes. Only
      the fourth criterium, namely the induction of the disease by immunization with an
      autoantigen, has so far not been met. As is the case for many, if not most,
      autoimmune diseases, the pathogenesis of IDDM is, however, far from being totally
      understood. Many aspects including the circumstances favoring escape from self
      tolerance, the role of the genetic background, the nature of the pancreatic
      antigens involved in the initiation and perpetuation of the disease, the effector
      mechanisms responsible for the elimination of the insulin cells and, most
      importantly, the conditions for restoring tolerance are at the forefront of
      immunopathologists' concerns. We provide in this review an account of the present
      situation in these different areas of research. There is no doubt that a cure or
      a prevention of the disease will be available in the forseeable future.
      Experiments on animal models have already initiated several clinical trials and
      epidemiological studies, and this is probably only the beginning of a long list.

PMID- 8555998
TI  - The use of oral tolerance as a therapy for ocular autoimmunity.
AB  - Mucosal surfaces throughout the body are the main protective structures against
      the heavy antigen burden from the environment. The ability to distinguish between
      noxious agents that should be kept in check and innocuous or beneficial
      substances that should be ignored is one of the most interesting phenomenon in
      immunology. Oral tolerance is the phenomenon by which exposure to a soluble
      antigen through the mucosal surface results in subsequent inability to mount an
      immune response to the same antigen upon challenge by a different route. This
      type of tolerance-inducing mechanisms has been recognized for many years as an
      effective approach to induce peripheral tolerance to soluble proteins. Recent
      achievements in the use of oral tolerance in the treatment of autoimmune diseases
      are reviewed here. Special emphasis is placed on the use of this
      immunotherapeutic approach to uveitis. The role of cytokines, CD4+ cells, CD8+
      cells, as well as the putative mechanisms by which oral tolerance is induced, are
      discussed.

PMID- 8555999
TI  - Proceedings of the 3rd annual meeting of the Canadian Society for Exercise
      Physiology. Quebec City, Quebec, Canada, October 26-28, 1995. Abstracts.

PMID- 8556000
TI  - The Role of General Practice in Maternity Care. Royal College of General
      Practitioners. Report of the RCGP Maternity Care Group.

PMID- 8556001
TI  - Dietary L-arginine attenuates blood pressure in mineralocorticoid-salt
      hypertensive rats.
AB  - The present study was designed to investigate the influence of dietary L-arginine
      supplementation on blood pressure and on ex vivo vascular reactivity in
      mineralocorticoid-salt (DOCA-salt) hypertensive rats. Systolic blood pressure and
      heart rate were determined throughout the experimental period in unanaesthetized
      rats. Plasma and urine electrolyte levels were measured. Vasoconstrictor response
      to noradrenaline and vasodilator responses to acetylcholine and sodium
      nitroprusside were evaluated in the isolated perfused mesenteric vascular bed.
      DOCA-salt hypertensive rats were divided into 2 groups: a control group and a
      treated group receiving 0.8% L-arginine supplementation in drinking water.
      Dietary L-arginine supplementation attenuated systolic blood pressure in
      conscious DOCA-salt hypertensive rats, but did not modify heart rate. Plasma
      calcium and sodium concentrations and urinary magnesium excretion were decreased
      by L-arginine supplementation. Noradrenaline-induced vasoconstriction decreased
      and acetylcholine-induced vasodilatation increased, whereas sodium nitroprusside
      induced vasodilatation was not modified, in the L-arginine-supplemented rats. It
      is concluded that dietary L-arginine supplementation in the diet lowers systolic
      blood pressure in DOCA-salt hypertensive rats, probably through vascular action.

PMID- 8556002
TI  - Cardiorespiratory responses to acute hypoxia and hyperoxia in adult and neonatal
      spontaneously hypertensive and normotensive rats.
AB  - The aim of this study was to investigate whether there are differences between
      particular characteristics of breathing regulation in primary hypertensive and
      normotensive states which might indicate significant differences in arterial
      chemoreceptor reflex function. Under air-breathing conditions, minute ventilation
      was similar in adult spontaneously hypertensive rats (SHR) (50 +/- 2ml/min x 100
      g) and in Wistar-Kyoto rats (WKY) (54 +/- 3 ml/min x 100 g) but significantly
      lower in randomly bred normotensive Wistar rats (NWR) (39 +/- 1 ml/min x 100 g).
      In seven-day-old rats minute ventilation was 10.5 +/- 1.2ml/min x 10 g in SHR and
      10.2 +/- 1.4 ml/min x 10 g in WKY. Our data indicate that there is no elevation
      of the ventilatory drive under air-breathing conditions which can be
      unequivocally associated with primary hypertension in adult and neonatal animals.
      Acute inhibition of ventilation caused by hyperoxia indicated that oxygen
      dependent peripheral chemoreceptor activity during air-breathing was similar in
      SHR and normotensive controls both in the unanesthetized neonatal state and in
      anesthetized adult animals. No well defined association between the
      characteristics of the hypoxic ventilatory response and primary hypertension
      could be demonstrated although responses in adult anesthetized SHR tended to be
      faster and of higher amplitude than in normotensive controls.

PMID- 8556003
TI  - Significance of renal kininases in patients with primary aldosteronism.
AB  - To elucidate the significance of renal kininases in primary aldosteronism (PA),
      urinary total kininase, kininase I, II and neutral endopeptidase 24.11 (NEP) were
      examined and evaluated for the regulation mechanisms of these kininases. Total
      kininase, kininase I and NEP were significantly higher in PA than in
      normotensives (NT), whereas no difference was found for kininase II. Moreover,
      42% of total kininase consisted of unknown kininase(s), different from kininase
      I, II or NEP. There were significantly positive correlations between plasma
      aldosterone concentration and total kininase, kininase I and unknown kininase(s)
      in PA. After the adrenalectomy, urinary kininases decreased into normal ranges,
      and unknown kininase(s) were negligible. These findings suggested that: 1)
      kininase I and NEP are accelerated in PA; 2) unknown kininase(s) differing from
      kininase I, II or NEP may exist in PA; 3) mineralocorticoids may regulate renal
      kininases; and 4) accelerated renal kininases may play some role in disorders of
      the renal water-sodium metabolism and in high blood pressure in PA.

PMID- 8556005
TI  - The World Hypertension League: goals and perspectives.
AB  - The World Hypertension League (WHL) is a federation of currently 51 national and
      regional organizations, committed to the prevention of hypertension. The
      objectives of the WHL are to promote the prevention, detection, and control of
      hypertension in populations by liaising with the member organizations, promoting
      the exchange of information among them, and offering internationally applicable
      methods and programs for hypertension control. This article describes objectives
      and policies, as well as projects and ongoing activities of the WHL

PMID- 8556004
TI  - Augmentation of coronary blood flow by ACE inhibition: role of angiotensin and
      bradykinin.
AB  - Inhibition of the angiotensin converting enzyme (ACE) is known to enhance
      coronary blood flow via partial suppression of angiotensin II and potentiation of
      bradykinin. The purpose of these experiments was to evaluate the contribution of
      each of these mechanisms to the ACE inhibition induced changes in blood flow in
      myocardial regions perfused by intact or stenotic coronary arteries. Seven
      domestic swine were submitted to an 82% stenosis of the left anterior descending
      artery with the circumflex artery left intact to serve as control area. Regional
      coronary blood flows were measured by the radioactive microsphere technique in
      the total area perfused by each coronary artery and in the subepicardial and
      subendocardial regions of each area separately, at rest and after treatments with
      captopril, losartan and a bradykinin antagonist given consecutively. We found a
      significant increase of total flow in both the stenotic and intact areas after
      captopril. Losartan caused a significant fall in systemic blood pressure with no
      further changes in overall coronary blood flow and the bradykinin antagonist
      produced a small but nonsignificant decline in total coronary flow. However,
      further separate analysis of subregions showed that subendocardial regions had a
      sharper increase in flow after captopril, and a significantly greater decline
      after bradykinin inhibition than subepicardial regions, whereas losartan tended
      to shunt blood from the subendocardial to the subepicardial regions. The results
      indicate that augmentation of coronary blood flow after ACE inhibition is not
      further enhanced by angiotensin II blockade and is in part mediated via
      potentiation of endogenous bradykinin, which exerts a preferential vasodilatory
      effect on the subendocardial regions of the myocardium.

PMID- 8556006
TI  - Outcomes of black and white hypertensive individuals after 30 years of follow-up.
AB  - Outcomes of a 30-year follow-up for the participants of the Charleston Heart
      Study were studied with elevated blood pressure assessed using various
      classifications. The traditional categories of > or = 140/90 mmHg, > or = 160/95
      mmHg and isolated systolic hypertension, as well as high normal and the four
      stages of high blood pressure were utilized in analyses. Prevalence rates of
      hypertension were, in general, higher among blacks compared to whites. Blacks had
      higher prevalence rates of hypertension and greater prevalence of high blood
      pressure at younger ages. Risk ratios were higher for black and white
      hypertensives than their normotensive counterparts. Blacks were found to have
      substantially higher population attributable risk proportions, particularly at
      the higher blood pressure categories. The results suggest that the standard
      clinical classifications of hypertension as related to mortality are appropriate
      for blacks and white.

PMID- 8556007
TI  - The place of hypertension control in total cardiovascular health: perspectives
      outlined by the Victoria Declaration.

PMID- 8556008
TI  - Elements of hypertension control policies.

PMID- 8556009
TI  - The therapeutic approach to the control of hypertension. Its impact on health
      policy.
AB  - The pharmacologic approach to the control of hypertension must consider both the
      clinical perspective and the Public Health approach policy in which social costs
      have to be balanced against benefits to the entire population. Cost-effectiveness
      analysis are at the core of decisions taken within this frame of reference. The
      issue of cost-effectiveness of preventive and therapeutic measures are crucial in
      the case of less developed countries. An analysis of studies undertaken in Mexico
      leads to the conclusion that, from a Public Health perspective, a program for the
      control of hypertension with a strong emphasis on drug therapy is likely to
      require a significant proportion of the health budget. Therefore, more emphasis
      must be placed on primary prevention based on modifications of life style.

PMID- 8556010
TI  - The epidemiology of hypertension control in populations.
AB  - Despite an aging population, prevalence rates for hypertension in the U.S. remain
      stable due to a decrease in rates in women but a corresponding increase in rates
      for men. Epidemiological factors which may contribute to these rates are
      discussed. The lack of a threshold for the association between blood pressure and
      disease events means that the majority of events occur in the larger number of
      people with mild disease. Because the efficacy and cost-effectiveness of medical
      therapy to lower mildly elevated blood pressure remains controversial, population
      based strategies to effect behavior change are the most prudent course for this,
      the largest group at risk. Targeted, resource-intensive medical intervention for
      those at high risk combined with hygienic measures for the population with mildly
      elevated blood pressure from the basis for an effective public health strategy.

PMID- 8556011
TI  - Well-being and treatment satisfaction in adults with diabetes: a Swedish
      population-based study.
AB  - In order to implement the St Vincent Declaration programme, instruments for
      quality assurance of medical outcomes as well as measures of psychological
      outcomes of diabetes care had to be developed. This paper presents baseline
      values for three questionnaires measuring psychological Well-being, Treatment
      Satisfaction and General Health among a representative sample of adult people
      with diabetes in Sweden consisting of 423 individuals of which 153 were insulin
      treated and 270 were diet/tablet-treated. Cronbach's alpha indicated that each of
      the Well-being and Treatment Satisfaction subscales was internally reliable,
      alphas ranging from 0.66-0.88. Factor analysis resulted in identification of five
      subscales (depression, anxiety, positive well-being, treatment satisfaction and
      metabolic control). There was no relation between any of the quality of life
      subscales with HbA1c, BMI, duration of diabetes, frequency of blood glucose tests
      per day, insulin regimens or diabetic complications. Females reported a more
      negative impact of diabetes on daily life compared with males (p < 0.001). In
      conclusion, the Well-being and Treatment Satisfaction scales are reliable for
      quality assurance purposes in diabetes while the briefer general health
      instrument provides a useful assessment of the global impact of a chronic
      disease.

PMID- 8556012
TI  - Measurement of the quality of life in cancer survivors.
AB  - A QOL instrument was developed to measure the specific concerns of long term
      cancer survivors. The QOL-CS is based on previous versions of the QOL instrument
      developed by researchers at the City of Hope National Medical Centre (Grant,
      Padilla, and Ferrell). This instrument was revised over a one year pilot by
      Hassey-Dow and Ferrell. The revised instrument included 41 items representing the
      four domains of quality of life incorporating physical, psychological, social,
      and spiritual well being. The present study was conducted as a mail survey to the
      membership (n = 1,200) of the National Coalition for Cancer Survivorship with 686
      subjects responding to the survey. This survey included a Demographic tool, QOL
      CS and the FACT-G tool developed by Cella. Psychometric analysis, performed on
      686 respondents, included measures of reliability and validity. Two measures of
      reliability included test-retest and internal consistency. The overall QOL-CS
      tool test-retest reliability was 0.89 with subscales of Physical r = 0.88,
      Psychological r = 0.88, Social r = 0.81, and Spiritual, r = 0.90. The second
      measure of reliability was computation of internal consistency using Cronbach's
      alpha coefficient as a measure of agreement between items and subscales. Analysis
      revealed an overall r = 0.93. Subscale alphas average ranged from r = 0.71 for
      spiritual well being, r = 0.77 for physical, r = 0.81 for social, and r = 0.89
      for psychological. Several measures of validity were used to determine the extent
      to which the instrument measured the concept of QOL in cancer survivors. The
      first method of content validity was based on a panel of QOL researchers and
      nurses with expertise in oncology. The second measure used stepwise multiple
      regression to determine factors most predictive of overall QOL in cancer
      survivors. Seventeen variables were found to be statistically significant
      accounting for 91% of the variance in overall QOL. The fourth measure of validity
      used Pearson's correlations to estimate the relationships between the subscales
      of QOL-CS and the subscales of the established FACT-G tool. There was moderate to
      strong correlation between associated subscales including QOL-CS physical to FACT
      physical (r = 0.74), QOL-CS Psych to FACT Emotional (r = 0.65), QOL Social to
      FACT Social (r = 0.44). The overall QOL-CS correlation with the FACT-G was 0.78.
      Additional measures of validity included correlations of individual items of the
      QOL-CS tool, factor analysis, and construct validity discriminating known groups
      of cancer survivors. Findings demonstrated that the QOL-CS and its subscales
      adequately measured QOL in this growing population of cancer survivors.

PMID- 8556014
TI  - Psychometric properties of a specific quality of life questionnaire in angina
      pectoris patients.
AB  - This paper describes the psychometric properties of the French version of the
      APQLQ (Angina Pectoris Quality of Life Questionnaire), that is to say, scaling
      assumptions, reliability and validity. This disease-specific Swedish
      questionnaire provides a global score as well as four subscores measuring
      physical activities, somatic symptoms, emotional distress, and life satisfaction.
      The French version was produced according to the forward-backward translation
      methodology. In a cross-sectional study, 183 coronary patients filled out the
      APQLQ and the MOS (Medical Outcomes Study) SF-36; 170 sent it back; the rate of
      missing data was low (1.3%). The factorial structure and the high level of inter
      scale correlations (> 0.60) suggested that the APQLQ measured one global concept
      rather than separate domains. The multitrait analysis identified one problematic
      item correlated strongly with all domains. The internal consistency was good
      (alpha Cronbach > 0.70). The correlations with the SF-36 scales were consistent
      with what was expected. The distribution of the scores of the APQLQ according to
      the clinical severity of Angina Pectoris (AP) was as hypothesized: the more
      severe the AP, the more impaired the Quality of Life. The score significantly
      discriminated between symptomatic (n = 110) and asymptomatic patients (n = 60)
      except for the emotional distress scale (p = 0.14). We recommend to analyze the
      French APQLQ as an index rather than as a profile. Its reliability, concurrent
      and clinical validity allowed its use in clinical trials.

PMID- 8556015
TI  - Quality of life bibliography and indexes: 1994 update.

PMID- 8556013
TI  - Measuring health-related quality of life in persons with genital herpes.
AB  - A disease-specific measure was needed for use in an international clinical trial
      to evaluate an investigational drug for genital herpes. A new measure was
      developed initially in the UK and translated and adapted for use in France,
      Italy, Germany, Denmark, Spain and the USA. This paper describes the translation
      and adaptation of the USA measure. It also describes the assessment of internal
      consistency, reproducibility, content validity, and construct validity
      (convergent and discriminant) of the measure. Two outcome measures of the final
      genital herpes-specific measure were developed: (1) a 21-item symptoms subscale;
      and (2) a 20-item HRQOL subscale. Each measure was scored and analyzed
      separately; the psychometric testing discussed in this paper refers to the HRQOL
      subscale only. The internal consistency of the HRQOL subscale is high (r = 0.93),
      as is the reproducibility measured with a two week interval (r = 0.85).
      Convergent validity is moderate to high. (Fleming Self-Regard subscale, r = 0.48;
      SF-36 Social Functioning dimension r = 0.59; SF-36 Mental Health dimension r =
      0.50). The number of herpes outbreaks in the past year was a significant
      predictor of scores on the HRQOL subscale (0-1 outbreaks, mean = 82.1; 2+
      outbreaks, mean = 72.1, p = 0.058) suggesting discriminant validity. The measure
      is currently in a phase III clinical trial including anti-viral therapy where the
      question of responsiveness can be addressed.

PMID- 8556016
TI  - Interrupting the binge-purge cycle in bulimia: the use of planned binges.
AB  - OBJECTIVE: To describe the rationale and use of a new procedure aimed at bringing
      binge/purge behavior directly under therapeutic control via the use of planned
      binges. METHOD: Research investigating the specific effects of the various
      cognitive and behavioral components of the standard cognitive-behavioral
      treatment (CBT) approach for bulimia nervosa is examined in combination with
      comprehensive reviews of the treatment outcome literature. RESULTS: These reviews
      suggest that while treatment has largely been effective at reducing binge-purge
      frequencies, it does not result in the elimination of the presenting problem for
      a significant proportion of participants. Evidence is presented to suggest that
      this may be accounted for by cognitive-behavioral approaches employing indirect
      procedures to bring the disordered patterns of eating under control. The
      application of the planned binge approach is illustrated by two cases treated at
      the University of New South Wales Post Graduate Psychology Clinic. DISCUSSION:
      These cases in combination with the analysis of the potential deficits of the
      standard behavioral procedures employed in CBT provide tentative support for the
      use of planned binges as an addition to the strategies currently used in the
      treatment of binge and purge behavior. In conclusion the paper explores some of
      the ethical implications raised by asking subjects to engage in their problematic
      behavior.

PMID- 8556017
TI  - The spectrum of eating disturbances.
AB  - OBJECTIVE: The purpose of this paper was to review and summarize the research
      literature on the spectrum of eating disturbances. METHOD: Literature was
      searched using a computer data base to identify recent articles related to the
      prevalence and occurrence of disturbed eating patterns as well as full and
      partial syndrome eating disorders (EDs). RESULTS: This review indicates that the
      prevalence of partial syndrome EDs in nonclinical populations is at least twice
      that of full syndrome EDs, and that there is a progression in some individuals
      from less to more severe disturbances in eating behavior. DISCUSSION: These
      findings suggest the need for careful, scientific evaluation of risk factors for
      EDs in both children and adults. A longitudinal research program in progress is
      described which aims to identify the risk factors for EDs.

PMID- 8556018
TI  - Development of body image, eating disturbance, and general psychological
      functioning in female adolescents: covariance structure modeling and longitudinal
      investigations.
AB  - OBJECTIVE: Covariance structure modeling (CSM) and longitudinal analyses were
      used to identify a possible causal sequence for factors that might lead to the
      development of body image and eating disturbance in adolescent females. METHOD:
      In Study 1, subjects were measured for level of obesity, perceived weight status,
      maturational timing, history of being teased about weight/size, body image,
      eating disturbance, and global psychological functioning. Study 2 was a
      systematic replication of Study 1 using different indices of body image and a
      more comprehensive assessment of eating disturbance. In Study 3, subjects from
      Study 1 were reassessed at a 3-year follow-up. RESULTS: The findings from Study 1
      indicated that level of obesity and perceived weight, but not maturational
      timing, had a directional influence on the other variables. In addition, teasing
      history was significantly related to the development of body image and eating
      disturbance. CSM and path analyses with Studies 2 and 3 data generally replicated
      and extended the results from Study 1. DISCUSSION: These findings offer important
      insights into possible causal sequences for the development of body image and
      eating disturbance.

PMID- 8556019
TI  - The Yale-Brown-Cornell Eating Disorder Scale: a new scale to assess eating
      disorder symptomatology.
AB  - Anorectic and bulimic patients (n = 100) were interviewed using the Yale-Brown
      Cornell Eating Disorder Scale (YBC-EDS). All patients reported preoccupations and
      rituals related to their eating disorder ranging from mild to severe
      symptomatology, with mean scores in the moderate range. The preoccupations were
      more severe than the rituals; however, the rituals were still time-consuming,
      distressing, and interfered with functioning. Both preoccupations and rituals
      were largely ego syntonic. The YBC-EDS is an easy to administer interview which
      characterizes and quantifies preoccupations and rituals associated with eating
      disorders. It is useful both for research and clinical purposes.

PMID- 8556020
TI  - Dietary helplessness and disinhibition in weight cyclers and maintainers.
AB  - OBJECTIVE: The primary purpose of this study was to compare obese versus nonobese
      adults and weight cyclers versus maintainers on measures of dietary helplessness,
      nutrition concern, dietary restraint, and disinhibition. METHOD: Dietary
      helplessness, nutrition concern, dietary restraint, and disinhibition were
      assessed in 385 healthy obese and nonobese men and women in the RENO Diet-Heart
      Study, a 5-year prospective investigation of cardiovascular risk factors, weight
      cycling, and lifestyle. RESULTS: The results indicated that dietary helplessness
      and disinhibition were significantly greater in obese individuals, subjects with
      a history of weight cycling, and weight fluctuators (prospectively measured).
      Women were found to score significantly higher than men on measures of dietary
      helplessness, disinhibition, and cognitive restraint. DISCUSSION: The role of
      nutrition attitudes is discussed in relation to dietary self-regulation, weight
      fluctuation, and management of body weight.

PMID- 8556021
TI  - Vitamin status of eating disorder patients: relationship to clinical indices and
      effect of treatment.
AB  - Vitamin abnormalities in eating disorder patients may contribute to altered
      neuropsychological status and the development of sequelae such as cognitive
      dysfunction. We examined the relationship between vitamin status and clinical
      indices in 13 low-weight patients with anorexia or bulimia nervosa at admission
      to a treatment program. Vitamin status was evaluated again at discharge (2-6
      weeks later) in nine of these patients. Four patients (31%) initially had
      erythrocyte enzyme activity indices suggesting deficiency for riboflavin and for
      vitamin B-6. Patients with biochemical evidence for riboflavin deficiency had
      lower relative body weight than those with normal riboflavin status (p < .02).
      Three patients (23%) had elevated plasma cholesterol concentrations (> 5.69
      mmol/L). Plasma retinol concentrations were within the normal range. Plasma alpha
      tocopherol concentrations were positively associated with serum albumin (p <
      .04), cholesterol (p < .0003), and total lipids (p < .0003), and were inversely
      associated with body mass index (p < .04). At discharge, thiamin, riboflavin and
      vitamin B-6 status indicators were normal in all cases examined. Suboptimal
      vitamin status is common in eating disorder patients but is normalized with
      dietary intervention and nutritional rehabilitation.

PMID- 8556022
TI  - An epidemiological study of eating disorders in Norwegian psychiatric
      institutions.
AB  - OBJECTIVE: The aim was to establish the prevalence of eating disorders in
      psychiatric patients. METHOD: The total inpatient (n = 8,942) and outpatient (n =
      10,125) Norwegian psychiatric population was investigated with a staff-report
      questionnaire. RESULTS: The prevalence of eating disorders in the inpatient
      population was 3.8% for women and 1.6% for men. In the outpatient population, the
      differentiated diagnoses anorexia nervosa (AN), bulimia nervosa (BN), and the
      comorbidity of AN+BN was 5.7%, 7.3%, and 1.6% for women, and 0.8%, 0.7%, and 0.3%
      for men (this could be reduced to AN and BN prevalences of 7.3% and 8.9% for
      women and 1.0% and 1.0% for men). DISCUSSION: The level of the prevalence figures
      is in the expected area, thus the present study confirms earlier studies with
      smaller psychiatric populations.

PMID- 8556023
TI  - Total body potassium and serum potassium among eating disorder patients.
AB  - OBJECTIVE: The purpose of the study was to determine body composition, including
      total body potassium (TBK+), serum potassium, and lean body mass (LBM), in
      anorexia nervosa. METHOD: TBK+ measurements, serum potassium levels, and
      anthropometric measurements were obtained from four anorectic patients in the
      first week after their hospital admission. All four patients had normal serum
      potassium levels but three of the four had significant depletion of total body
      potassium. Two methods of calculating LBM, based on TBK+ measures or
      anthropometric assessment, produced different results. RESULTS: TBK+ may be
      depleted even when serum potassium levels are normal. It was also concluded that
      the two methods of calculating LBM were inaccurate. DISCUSSION: Patients may be
      at risk for cardiac arrhythmias and other physiological abnormalities even when
      serum potassium is normal since TBK+ may be low. The need for comprehensive
      assessment of body composition based on four compartment models is discussed.

PMID- 8556024
TI  - Stroop interference and food intake.
AB  - OBJECTIVE: The Stroop task is aimed at assessing attentional bias. Words are
      displayed one by one on a computer screen and subjects are instructed to name the
      color in which every word is printed. The attentional bias is supposed to be
      reflected in the extent to which the word meanings interfere with the speed of
      color naming: The longer the color naming latency, the larger the attentional
      bias. Experiments using this task have demonstrated attentional bias for eating
      and body shape-related words in bulimic, anorexic, and restrained subjects.
      Explanations of these results have generally been formulated in terms of
      restricted food intake or emotional concerns about food and body shape-related
      themes. In contrast, in the present article it was proposed that Stroop
      interference might reflect a tendency either to withdraw or approach food or body
      shape-related stimuli. METHOD: Fifty-one subjects (25 unrestrained, 26
      restrained) were administered a Stroop task containing neutral, food, and body
      shape-related words. There were two conditions to which subjects were randomly
      allocated: the "appetizer" and "no-appetizer" condition. The appetizer was a bit
      of pudding to be ingested by the subject just before the Stroop task. Following
      the Stroop task an ice cream taste test was presented in which the subjects were
      allowed to eat as much as they liked. The amount of ice cream eaten was
      registered secretly. RESULTS: The results show that in unrestrained subjects
      Stroop interference for food words was found only in the appetizer condition.
      Restrained subjects, however, showed a permanent interference for food words. A
      significant correlation of .58 between Stroop food-word interference and ice
      cream intake was found only in unrestrained subjects. In restrained eaters the
      correlation was near 0. No effect of condition or restraint was found on Stroop
      body shape-word interference. DISCUSSION: The findings indicate that (1)
      ingestion of an appetizer seems to have evoked an attentional bias for food words
      in nonrestraints that correlated with food intake; (2) restrained eaters showed
      continuous attentional bias. This appears to support the urge-to-act explanation
      of Stroop interference. The lack of correlation between restraints' attentional
      bias and ad lib food intake could have been caused by inhibition of approach
      which is one of the characteristics of restrained eating: The present procedure
      seems not to have triggered disinhibited eating in these subjects. Among other
      things it is concluded that Stroop interference, as a measure of "craving"
      triggered by food cue, might be a useful aid in assessing the risk of relapse in
      treated binge eating patients.

PMID- 8556025
TI  - Cognitive style of patients with anorexia nervosa and bulimia nervosa.
AB  - Nine female patients with anorexia nervosa and 7 female patients with bulimia
      nervosa were assessed on the Matching Familiar Figures Test (MFFT). This study
      found that subjects with bulimia nervosa responded more quickly than did the
      anorexic subjects. Results such as these suggest that not only are bulimic
      patients more behaviorally impulsive than anorexic patients, they are also more
      cognitively impulsive. Patients with anorexia nervosa in contrast seemed to
      display a reflective cognitive style. Extreme cognitive styles may contribute to
      resistance in treatment and/or relapse in anorexia or bulimia nervosa.

PMID- 8556026
TI  - Binge eating disorder, retention, and dropout in an adult obesity program.
AB  - OBJECTIVE: The purpose of this study was to identify factors associated with
      dropout in a weight reduction program among obese, nonpurging binge and nonbinge
      eaters. METHOD: We categorized 156 obese, nonpurging women previously randomized
      to a behavior modification-based (BM) or a food addiction theory-based (FD)
      weight reduction intervention by binge status using the DSM-IV criteria for binge
      eating disorder (BED). Subjects were monitored prospectively for dropout during
      the 6-month intervention period. RESULTS: Results of a Cox proportional hazards
      survival analysis indicated binge status had a statistically significant (p =
      .04) protective effect against dropout. Binge eaters were half as likely to
      dropout versus nonbinge eaters. DISCUSSION: We conclude that (1) the DSM-IV
      criteria for BED is a useful method of classifying obese individuals in weight
      loss interventions and (2) the identification of subgroups among obese subjects
      is an important step in understanding retention in weight loss programs. Future
      research can confirm this finding.

PMID- 8556027
TI  - Distorting reality for children: body size proportions of Barbie and Ken dolls.
AB  - Using hip measurements as a constant, calculations were made to determine the
      changes necessary for a young, healthy adult woman and man to attain the same
      body proportions as Barbie and Ken dolls, respectively. Among the changes
      necessary were for the female to increase 24 in. in height, 5 in. in the chest,
      and 3.2 in. in neck length, while decreasing 6 in. in the waist, and for the male
      to increase 20 in. in height, 11 in. in the chest, and 7.9 in. in neck
      circumference. Like adults, children are exposed to highly unrealistic ideals for
      shape and weight.

PMID- 8556028
TI  - A practical guide to prescribing estrogen replacement therapy.
AB  - Discounting vaccinations, menopausal hormone replacement constitutes the most
      widely practiced form of long-term prophylactic therapy. Long acknowledged as a
      means of retarding net bone density loss, sufficient data have accumulated to
      document the cardioprotective aspects of estrogen replacement therapy (ERT). Not
      surprisingly, new questions concerning long-term effects on various tissues and
      interaction with progestins have arisen. Given that ERT alone increases risk for
      endometrial cancer to unacceptable levels, addition of progestins can fully
      obviate that risk. To what extent, however, do various progestins mute the
      beneficial estrogen effect on cholesterol lipoproteins and locally in the
      arterial wall? Does long-term ERT increase the risk for breast cancer and who is
      at greatest risk? Does the route of ERT matter with respect to metabolic changes?
      Considering that a woman may spend fully one third of her life in the
      postmenopausal state, it behooves physicians as primary care providers and as
      consultants to understand the pros and cons of ERT. Modulation of dose, route and
      agent, as well as the protocol for therapy, all affect long-term patient
      compliance. In order to sustain motivation, education of the patient is
      mandatory, and that process starts with the physician.

PMID- 8556029
TI  - Visual findings and histologic diagnosis of pelvic endometriosis under
      laparoscopy and laparotomy.
AB  - OBJECTIVE: To assess the diagnostic value of visual findings in the diagnosis of
      endometriosis from the histological point of view. STUDY DESIGN: 212 specimens
      from 107 patients with benign (74.8%) or malignant (25.2%) disease were obtained
      by biopsy or resection under laparoscopy (65 patients) or laparotomy (42
      patients). Ages ranged from 19 to 62 (mean age 36.4). Visual findings were
      classified according to the criteria established by the Endometriosis Committee
      of the Japan Society of Obstetrics and Gynecology in 1993. Specimens were stained
      with hematoxylin-eosin, and 15 cases with periodic acid-Schiff stain or silver
      impregnation stain. RESULTS: Among pigmented lesions, endometriosis was found in
      73.0% of specimens from the pelvic peritoneum and in 56.4% of those from the
      ovaries. Blueberry spots in the pelvic peritoneum as well as ovarian chocolate
      cysts showed the highest positive rate. In the presence of multiple or complex
      pigmented lesions of the pelvic area, the rate was still higher (88.6%). Those
      rates were due to our inclusion of inaccurate and incomplete biopsy specimens.
      Endometriosis of nonpigmented lesions was found in only 11 patients (12.0%) who
      also had pigmented lesions and/or adenomyosis. CONCLUSION: The laparoscopic
      diagnosis of endometriosis can be made only when multiple complex pigmented
      lesions are observed, but, otherwise, histopathological confirmation is
      necessary.

PMID- 8556030
TI  - Human embryo co-culture: results of a randomized prospective study.
AB  - OBJECTIVE: To evaluate in vitro culture of human embryos in the presence or
      absence of a Vero cell monolayer. DESIGN: Randomized prospective analysis.
      PATIENTS: Seventy-five couples were randomly allocated to either an experimental
      study group (embryos in co-culture) or a control group. RESULTS: A significantly
      higher cleavage rate (92%) was obtained in the co-culture group compared with the
      control group (83%). In addition, a higher percentage of morphologically superior
      embryos was observed in the co-culture group than in the control group, although
      no significant difference was found between the two groups in blastocyst
      development or clinical outcome. CONCLUSIONS: When taking final clinical results
      into consideration in a routine IVF program, the conventional method provides
      more practicality and efficiency if transfers are performed on either day 2 or 3.
      However, if embryos remain in culture, co-culture systems allow for replacements
      or cryopreservation at the blastocyst stage.

PMID- 8556031
TI  - Hemostatic effects of two oral contraceptives containing low doses of ethinyl
      estradiol and either gestodene or norgestimate: an open, randomized, parallel
      group study.
AB  - OBJECTIVE: To determine effects on blood clotting of two modern low-dose
      monophasic oral contraceptives. SUBJECTS AND METHODS: We measured in vivo markers
      of intravascular coagulatory and fibrinolytic activity in 40 volunteers randomly
      assigned to one of two low-dose oral contraceptives (OCs) for 6 months; one
      contained 35 micrograms of ethinyl estradiol (EE) plus 250 micrograms of
      norgestimate and the other, 30 micrograms of EE plus 75 micrograms of gestodene.
      RESULTS: Both formulations increased coagulatory as well as fibrinolytic activity
      over baseline: circulating reactive products of thrombin increased by 40%, and
      plasmin activity by 60%, after 3 months of treatment. Six months of OC use
      increased hemostatic activity substantially over that with 3 months of use.
      Differences between both OC formulations were marginal and clinically
      insignificant. CONCLUSION: The data suggest an EE-dose-dependent, balanced
      activation of in vivo coagulation and fibrinolysis in users of currently
      available, combined OCs. However, there is considerable consumption of
      coagulation inhibiting factors, suggesting that women with congenital
      deficiencies of antithrombin III and protein C should not use combined OCs.

PMID- 8556032
TI  - Menstrual characteristics of women suffering from insulin-dependent diabetes
      mellitus.
AB  - OBJECTIVE: To assess the frequency of menarche and menstrual disturbances among
      women suffering from insulin-dependent diabetes mellitus, and to evaluate their
      correlation to the onset of diabetes, its duration, and complications. RESEARCH
      DESIGN AND METHODS: Retrospective analysis of the menstrual regularity and
      gynecologic and fertility history of 100 women suffering from insulin-dependent
      diabetes mellitus. These data were compared with information obtained from the
      patients' medical records regarding the age at onset of diabetes, its management,
      control, and complications. RESULTS: The average age at menarche was 13.5 years.
      Delayed menarche tended to appear in girls whose diabetes was diagnosed before
      the age of menarche, and before the age of 10 years. Menstrual disturbances, such
      as oligomenorrhea, amenorrhea, and polymenorrhea, occurred in 32% of the women. A
      significant correlation was found between late menarche and menstrual
      disturbances. Furthermore, patients with diabetic complications had a higher
      incidence of menstrual disorders compared with uncomplicated diabetic patients.
      CONCLUSIONS: It appears that women with insulin-dependent diabetes mellitus who
      had been diagnosed prior to menarche had a higher probability of delayed
      menarche, and were at higher risk for development of menstrual disturbances,
      including amenorrhea with subsequent fertility disorders.

PMID- 8556033
TI  - Breast cancer risk among women using silicone gel breast implants.
AB  - Since their introduction in 1962, silicone gel-filled breast implants have been
      used by an estimated one to two million women. Questions concerning an increased
      cancer risk to these women have been raised. A review of the medical literature,
      including case reports, case series, physician surveys, case-control studies, and
      cohort studies, failed to turn up any evidence which associated the use of
      silicone breast implants with either an increased risk of breast cancer or an
      increased risk of a more advanced stage of cancer at the time of cancer
      diagnosis. The available data do not indicate any significant difference between
      the characteristics of the breast cancers of women with breast implants and those
      of women in control populations.

PMID- 8556035
TI  - Managed care hasn't curtailed high-tech tests.

PMID- 8556034
TI  - How some states rate on the health-o-meter.

PMID- 8556036
TI  - Eat, drink and file for disability.

PMID- 8556037
TI  - Who's paying for prescriptions?

PMID- 8556039
TI  - The great debate. Resolved, PSOs are going to be regulated. The question is, will
      they get what they want?
AB  - Insurers and others say that provider-sponsored organizations--better known as
      PSOs--are simply HMO wannabes and should be treated as such. Supporters counter
      that PSOs deserve a separate set of regulations. Both sides are scrambling to
      make their case as the debate moves from the offices of state legislators onto
      the national scene.

PMID- 8556040
TI  - 1996 NOVA Award. Breaking down barriers, building up hopes.
AB  - From Ohio to Nebraska to Arizona, community hospitals are taking more proactive
      steps to meet the needs of those who depend on their services-- and prevent
      health problems before they even happen. For their collaborative work, Hospitals
      & Health Networks and the American Hospital Association salute this year's NOVA
      Award winners.

PMID- 8556038
TI  - How one New York hospital is moving to head managed care off at the pass.
      Interview by Jim Montague.
AB  - Like tremors before an earthquake hits, managed care and projected cuts in
      Medicare and Medicaid are shaking up New York even before they arrive. Many of
      the city's largest hospitals hope to cushion the shock waves from lost referrals
      for inpatient care by buying primary care providers, though it's likely many of
      these efforts will be too little, too late. But a handful of New York's providers
      have been prepping for managed care's growth, allowing them to address it more on
      their terms. Mount Sinai Medical Center is so confident its advance work will
      succeed that it actually is adding a few beds, not closing them. John Rowe, M.D.,
      president of the medical center and the Mount Sinai School of Medicine, spoke
      recently with H&HN staff writer Jim Montague about Mount Sinai's strategies.

PMID- 8556041
TI  - Agency talk. With apologies to Mark Twain (and, for that matter, Newt Gingrich),
      reports of HCFA's death have been greatly exaggerated.
AB  - The Health Care Financing Administration continues to plug alone while it awaits
      word on what sort of job it will be required to do in the future. The ongoing
      battle over the scope of federal authority over Medicaid, as well as managed care
      driven changes in Medicare, will reshape the agency. Whatever the specifics,
      change is imminent.

PMID- 8556042
TI  - Coordinated care. Paving the road to Medicare savings.

PMID- 8556043
TI  - Wellness. Practicing what they preach.

PMID- 8556044
TI  - Physicians. Homegrown medical talent.

PMID- 8556045
TI  - Efficiencies. Fast track to cost-cutting.

PMID- 8556046
TI  - Technology. Plugged into the community.

PMID- 8556048
TI  - Specializing. Catering to seniors.

PMID- 8556047
TI  - Incentives. A payoff to get with the program.

PMID- 8556049
TI  - The law of large numbers.

PMID- 8556050
TI  - Immunoglobulin G can cross-react with glucagon antisera and cause a spuriously
      high plasma immunoreactive glucagon level.
AB  - We had a patient with asymptomatic hyper-immunoreactive glucagonemia and with no
      evidence of pancreatic tumor detected by radiological examinations. The glucagon
      level was not decreased by the administration of glucose or somatosatin analogue
      (SMS 201-995). Gel filtration studies revealed that most glucagon
      immunoreactivity was eluted at the position of 150,000 daltons [big plasma
      glucagon (BPG)]. Binding studies with 125I-glucagon showed that glucagon
      autoantibody was negative. Acid treatment of plasma and reduction of
      immunoglobulin G (IgG) did not result in a shift of BPG to normal glucagon (3485
      daltons). Glucagon immunoreactivity determined with anti-glucagon antiserum OAL
      123 (C-terminal specific antiserum used in the present radioimmunoassay kit) did
      not dilute out in parallel to normal glucagon (3485 daltons), and the plasma
      glucagon level was normal with Unger's 30K (anther C-terminal specific antiserum)
      and OAL 196 (N-terminal specific antiserum). The patient's IgG dose-dependently
      reduced the binding of 125I-glucagon to anti-glucagon antiserum OAL-123. Glucagon
      degrading activity (GDA) was negative in the patient's plasma. These results
      suggest that the patient's IgG cross-reacted with the present anti-glucagon
      antiserum OAL 123, and caused a spuriously high plasma immunoreactive glucagon
      level.

PMID- 8556051
TI  - Glycation accelerates the oxidation of low density lipoprotein by copper ions.
AB  - We investigated the in vitro effect of glycation on LDL oxidation. Native LDL
      (nLDL) was glycated in 0, 5, 10, or 20 mM glucose. This glycated LDL (gLDL) was
      oxidized by 1 microM copper ion. Compared to nLDL and gLDL, oxidized gLDL (ogLDL)
      has a greater negative charge. The thiobarbituric acid reactive substance (TBARS)
      value of ogLDL increased with the glucose concentration tested during glycation
      in a dose-dependent manner. OgLDL glycated in 20 mM glucose had a significantly
      higher TBARS level than did oxidized LDL incubated without glucose. In
      conclusion, LDL glycated in vitro is prone to oxidation. Thus, glycated LDL,
      which increases in the diabetic state, may contribute to the pathogenesis of
      atherosclerosis in diabetic patients.

PMID- 8556052
TI  - Immunohistochemical localization of epidermal growth factor and its effect on
      granulosa cell proliferation in rat ovary.
AB  - The localization of epidermal growth factor (EGF) in the ovary and its effect on
      proliferation of granulosa cells were investigated in gonadotrophin-primed
      immature female rats. Immunoreactions with anti-rat EGF monoclonal antibody were
      observed sparsely in the granulosa layer and antrum of follicles, but not in the
      theca layer or stromal tissue. The EGF-positive cells were round or oval shaped
      and often larger than granulosa cells. The localization and morphological
      appearances of these cells in the follicles were in good agreement with those of
      macrophages. Although EGF alone did not promote granulosa cell growth in vitro,
      the labelling index with [3H]thymidine of granulosa cells cultured with 0.1 ng/ml
      EGF and 0.1 ng/ml basic fibroblast growth factor was significantly greater than
      that without the growth factors (18.4% vs. 15.8%, P < 0.01). These results
      suggest that macrophages in follicles may modulate follicular development through
      a paracrine mechanism by secreting EGF and other growth factors.

PMID- 8556053
TI  - Adrenocorticotropic hormone (ACTH) increases the expression of its own receptor
      gene.
AB  - Regulation of the ACTH receptor (R) in the adrenal gland by its own ligand "ACTH"
      has been a matter of controversy. In the present study, whether ACTH regulates
      the expression of mRNA for its own receptor in the adrenal gland was studied in
      human subjects and in rats in vivo. In the human study, adrenal adenoma tissues
      as well as adjacent normal tissues were obtained at surgery from two patients
      with typical Cushing's syndrome. Northern blot analysis revealed two ACTH-R mRNA
      species with 4.0 kb and 2.0 kb. ACTH-R mRNAs in the adenoma tissues were much
      more abundant than those in the normal tissues from the two patients, suggesting
      that the mRNA in normal adrenal tissue is either suppressed by cortisol excess or
      the absence of ACTH. To examine the mechanism involved in ACTH-R mRNA regulation,
      the changes in the receptor mRNA caused by ACTH were studied in dexamethasone
      treated rats. Administration of dexamethasone for 5 days resulted in a marked
      decrease in ACTH-R mRNA to an undetectable level. A bolus administration of ACTH1
      24 intravenously or ACTH-Z1-24 intramuscularly to the dexamethasone-treated rat
      did not cause any significant change in ACTH-R mRNA from 0.5 to 12 h after the
      administration. However, a significant increase in the receptor mRNA was observed
      at 24 h after the ACTH-Z1-24 and the level was further increased until 48 h
      followed by a sustained increase at 72 h when it was given once every 24 h. These
      data suggest that the ACTH-receptor is increased by ACTH at a pretranslational
      level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556054
TI  - Characteristics of aldosterone-producing adenoma responsive to upright posture.
AB  - A small subgroup of primary aldosteronism due to aldosteronoma, named aldosterone
      producing renin-responsive adenoma (AP-RA), has been reported to masquerade as
      idiopathic hyperaldosteronism (IHA) because of the responsiveness of the plasma
      aldosterone concentration (PAC) to upright posture (UP). We found two patients
      with AP-RA in 19 patients with aldosteronoma who were examined by UP stimulation
      and were treated surgically. In 17 patients with typical aldosterone-producing
      adenoma (APA), PAC decreased or increased only slightly (less than 200% of the
      basal level); in contrast, it increased to over 300% of the basal level in two
      patients with AP-RA. The two groups were comparatively studied as to their
      hormonal levels, adrenal computed tomography (CT) scan and histological findings
      in order to clarify the characteristics of AP-RA. Basal PAC was within the normal
      range (11.1 and 13.0 ng/dl) in AP-RA but in APA it ranged from 14.8 to 58.1 ng/dl
      with a mean of 32.3 +/- 2.7 ng/dl. The diameters of the adenoma in AP-RA were
      apparently smaller (6 and 9 mm) than those in APA ranged from 10 to 25 mm with a
      mean of 15.5 +/- 1.1 mm. After a contrast medium was injected at CT scan, the
      density of the normal adrenal gland adjacent to the adenoma increased but that of
      the adenoma did not in APA, making a clear distinction between the adenoma and
      the gland. On the other hand, the density of the adenoma and gland increased to
      almost the same degree in AP-RA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556055
TI  - Inhibition of thyrocyte iodide uptake by H+K+ ATPase inhibitor, timoprazole.
AB  - The inhibitory effect of timoprazole on iodide uptake by cultured thyrocytes was
      observed using FRTL-5 cells. The inhibition was noticed to be dose dependent and
      was eliminated completely by rinsing. Timoprazole pretreated with acid had
      inhibitory effects, but [3H] leucine incorporation experiments indicated that
      acidified timoprazole inhibited protein synthesis to some degree. In addition,
      TSH-induced cAMP production was also inhibited by acidified timoprazole.
      Timoprazole pretreated in a neutral solution did not have any cytotoxic effects
      on TSH-induced cAMP production or protein synthesis at concentrations less than
      1000 microM, suggesting that timoprazole by itself has specific effects on iodide
      uptake. The absence of any direct interaction of the drug with iodide was
      confirmed by separation of timoprazole and iodide on a C18 Sep-Pak column. It is
      concluded that timoprazole by itself could inhibit iodide transport through the
      thyroid cell membrane. This may provide a useful system in further investigating
      the mechanism of iodide transport.

PMID- 8556056
TI  - The characteristics of nine patients with adrenal incidentalomas.
AB  - With the widening use of computerized tomography, the incidentaloma, an adenoma
      found incidentally in the adrenal, in computerized tomograms obtained for
      problems not necessarily related to the adrenal, has emerged as a recent clinical
      entity. Nine cases with such tumors are presented, here, along with a brief
      review of the related medical literature. Endocrine and other studies have shown
      that two of these nine patients had hormone secreting adrenal tumors, two
      pheochromocytomas. Surgical resection of the tumor was performed in six of the
      cases and aspiration biopsy was done in four with three completely benign
      cytological examination results (Class I or II) and one Class III result. The
      tumor with the class III result turned out to be a benign pheochromocytoma. CT
      estimates of the tumor size were 25 mm to 80 mm in the whole group and 30 to 80
      mm in the patients who were operated on. Operation and histopathologic
      examination revealed three cortical adenomas, two pheochromocytomas, and one
      myelolipoma. Although no malignant tumors were found, the percentage of
      functioning adrenal neoplasms is rather high (22.2%) in this group of nine
      incidentalomas. Cases of adrenal incidentaloma therefore require a thorough
      endocrine evaluation along with other examinations which allow the clinician to
      follow tumor size.

PMID- 8556057
TI  - Chlormadinone acetate as a possible effective agent for congenital adrenal
      hyperplasia to suppress elevated ACTH and antagonize masculinization.
AB  - We report two cases of congenital adrenal hyperplasia (CAH) in which
      administration of chlormadinone acetate (CMA), a substituted progestational agent
      for prostatic disease, suppressed ACTH hypersecretion and lowered plasma
      testosterone levels. Case 1 was 83-year-old male with advanced prostatic
      carcinoma and CAH due to 21-hydroxylase deficiency. His plasma testosterone did
      not decrease in spite of a bilateral orchiectomy. Case 2 was 40-year-old female
      with CAH due to 21-hydroxylase deficiency suffering from virilization after the
      cessation of cortisol supplement therapy because of her breast carcinoma. In
      these two cases, oral administration of CMA at a daily dose of 75-100 mg
      suppressed ACTH and cortisol to subnormal levels and reduced testosterone levels.
      With the suppressive effect on ACTH excess and antiandrogenic action, CMA may be
      suitable for patients with CAH suffering from symptoms due to overproduced ACTH
      or adrenal androgen.

PMID- 8556058
TI  - Possible pre-Cushing's syndrome due to an adrenal adenoma incidentally
      discovered.
AB  - We demonstrated the functional evaluation of adrenal incidentaloma in 8 patients
      who had no abnormal finding associated with Cushing's syndrome. Adrenal tumors
      were incidentally discovered by abdominal echogram in 5 patients and by computed
      tomography (CT) in 3 patients. Serum cortisol levels and urinary excretion of 17
      hydroxycorticosteroids (17-OHCS) were within normal limits in four of 8 patients.
      Urinary excretion of free cortisol was also within normal limits except for
      patient 8. Urinary excretion of 17-OHCS, however, was not suppressed by
      dexamethasone administration in five of 8 patients. Excretion of urinary 17-OHCS
      did not increase in response to metyrapone in 3 of 4 dexamethasone-insuppressible
      patients, but increased in 3 dexamethasone-suppressible ones. Serum cortisol
      increased in response to exogenous ACTH in all 6 patients examined. 131I
      Adosterol accumulation was found in only the tumor side in 7 patients and
      bilaterally in one patient. Adrenalectomy was done in 7 patients, and microscopic
      findings showed adrenocortical adenoma. Serum cortisol was significantly
      suppressed in response to dexamethasone in the post-operative stage in all 7
      patients examined. These results indicate that these adrenal incidentalomas seem
      to have a cortisol over-production which is dexamethasone-insuppressible and ACTH
      dependent, and that they can be classified as "Pre-Cushing's Syndrome."

PMID- 8556059
TI  - Mutations in the cysteine-rich region of the RET proto-oncogene in patients
      diagnosed as having sporadic medullary thyroid carcinoma.
AB  - Medullary thyroid carcinoma (MTC) and pheochromocytoma appear in either a
      sporadic or a hereditary form as components of multiple endocrine neoplasia
      (MEN). Many germline mutations of the RET proto-oncogene have been reported in
      patients with MEN 2A and 2B, and familial MTC (FMTC). To elucidate the
      etiological roles in tumorigenesis of sporadic MTCs and pheochromocytomas,
      mutations in the cysteine-rich region of the RET proto-oncogene were analyzed by
      using polymerase chain reaction-single strand conformation polymorphism (PCR
      SSCP) analysis. Exons 10 and 11 were studied in genomic DNAs from 3 clinically
      apparent sporadic MTCs, MTCs and pheochromocytomas from 2 patients with MEN 2A, 1
      with FMTC, 4 with MEN 2B, 3 with neurofibromatosis type 1 (NF1), 12 sporadic
      pheochromocytomas and an MTC cell line, TT. All tumors from two patients with MEN
      2A and one patient with FMTC had mutations at codon 618 and 634 as well as their
      leukocytes, reflecting their germline mutations. In this region, no mutations
      were detected in any tumors from patients with MEN 2B and NF1, and sporadic
      pheochromocytomas. But mutations were detected and identified in 3 clinically
      apparent sporadic MTCs and TT cells. A 6 base pair (bp) deletion causing the loss
      of a cysteine residue at codon 634 and a mutation causing substitution from
      cysteine to tyrosine at codon 634 were detected in 2 sporadic MTCs as somatic
      events. In a female patient diagnosed as having sporadic MTC, a mutation at codon
      618 was detected not only in tumor tissues, but also in her leukocytes,
      suggesting a germline mutation of the RET proto-oncogene.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8556060
TI  - Mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A
      (Sipple's syndrome).
AB  - Genetic linkage analyses have traced the loci for multiple endocrine neoplasia
      type 2A (MEN 2A) to an interval on chromosome 10q11.2. This region encompasses
      the RET proto-oncogene, a receptor tyrosine kinase gene expressed in medullary
      thyroid carcinoma (MTC) and pheochromocytoma. By means of genomic polymerase
      chain reaction (PCR) amplification and DNA sequencing, we have analysed 19
      individuals from two Japanese MEN 2A families for mutations of the RET proto
      oncogene in exons 10 and 11. We conducted single-strand conformational
      polymorphism (SSCP) analysis of the RET proto-oncogene amplified from affected
      and unaffected family members. The DNA alterations in the RET proto-oncogene
      caused substitution of a cysteine for a serine at codon 620 in the exon 10 in
      three patients in one MEN 2A family, 1, and of a cysteine for a tyrosine at codon
      634 in the exon 11 in six patients in the MEN 2A family, 2. We could find two
      asymptomatic MEN2A gene carriers who had no symptoms or signs of MEN 2A by DNA
      analysis of the RET proto-oncogene. No mutations in these exons were detected in
      any unaffected normal members of MEN 2A. A DNA alteration in the RET proto
      oncogene coding sequence in exon 10 caused a shift on SSCP gels that was
      characteristic of the disease chromosome in the MEN 2A family, present only in
      affected members of the family. The DNA change could also be detected by
      restriction enzyme digestion with RsaI in family 2. Two MEN 2A patients with a
      cysteine for a tyrosine substitution at codon 634 in the exon 11 had parathyroid
      hyperplasia. We conclude that the identification of a DNA alteration in the MEN2A
      gene will permit predictive molecular testing of individuals at risk in these MEN
      2A families and the PCR-restriction enzyme system will be useful for genetic
      diagnosis of members of these MEN 2A families. This information, by providing
      diagnostic certainty, should improve medical care for affected family members.

PMID- 8556061
TI  - Expression of prolactin gene in human decidua during pregnancy studied by in situ
      hybridization histochemistry.
AB  - The prolactin (PRL) gene is known to be expressed not only in the anterior
      pituitary but also in the decidualized human endometrium. This study was designed
      to detect the site of synthesis of PRL during pregnancy by in situ hybridization
      histochemistry. Decidual and trophoblast tissues from early pregnancy were
      obtained from patients undergoing therapeutic abortion at 8-10 weeks of
      gestation. Term placentae were obtained from patients with uncomplicated
      deliveries at 38-40 weeks. Sections of these tissues were hybridized with 35S
      labeled RNA probe complementary to human PRL mRNA. Specific hybridization signals
      were distributed over the decidual cells in early and term pregnancy. In the
      decidua capsularis of early pregnancy, labeled cells were concentrated close to
      the amniotic cavity, although decidual cells were distributed evenly. In the
      decidua parietalis, almost all decidual cells were labeled, but no specific
      labeling was seen in the endometrial glands or capillary endothelium. In the
      decidua basalis, greater signals were always detected over the decidual cells in
      early pregnancy than in term pregnancy, when sections, which were hybridized with
      the same probe and exposed simultaneously, were compared. No specific
      hybridization was detected in the trophoblast cells. These results not only
      confirm that PRL is specifically synthesized in the decidual cells but also
      indicate that there are regional and periodical differences in PRL gene
      expression in the decidual cells during pregnancy.

PMID- 8556062
TI  - Body composition assessed by bioelectrical impedance analysis (BIA) in patients
      with Graves' disease before and after treatment.
AB  - Body composition was assessed by bioelectrical impedance analysis (BIA) in 11
      female patients with Graves' disease and in 49 age-matched healthy Japanese
      women. Patients with Graves' disease were examined in the hyperthyroid state
      before treatment and in the stable euthyroid state after treatment with
      antihyroid drugs for 6 to 18 months. Body weight (BW), percent body fat (BF/BW),
      percent lean body mass (LBM/BW) and percent total body water (TBW/BW) were not
      statistically different between hyperthyroid Graves' patients and healthy
      subjects. Percent body cell mass (BCM/BW) was much lower in hyperthyroid Graves'
      patients than in healthy subjects (mean +/- SEM; 33.9 +/- 2.4% vs. 41.5 +/- 0.5%,
      P < 0.001). Percent ratio of extracellular water to total body water (ECW/TBW)
      was much greater in hyperthyroid Graves' patients than in healthy subjects (53.9
      +/- 3.0% vs. 41.8 +/- 0.5%, P < 0.001). These abnormal ratios, BCM/BW and
      ECW/TBW, were normalized after treatment. Serum free T4 levels showed a positive
      correlation with ECW/TBW (r = 0.779) and a reverse correlation with BCM/BW (r = 
      0.760) in all of the patients with Graves' disease examined. These findings
      indicate that body composition is affected by thyroid hormones and that body
      composition in hyperthyroid Graves' disease is characterized by decreased BCM
      associated with increased ECW.

PMID- 8556063
TI  - Increase in serum interleukin-6, plasma ACTH and serum cortisol levels after
      systemic interferon-alpha administration.
AB  - Systemic administration of human interferon-alpha stimulates the pituitary
      adrenal axis in men, but the exact mechanism still remains to be established. The
      present study was undertaken to examine the hypothesis that interferon-alpha may
      alter the circulating concentrations of the cytokines which involve the
      activation of the pituitary-adrenal axis. Eleven patients with chronically active
      hepatitis C were treated with human lymphoblastoid interferon-alpha (IFN: 6 x
      10(6) IU/day) and changes in plasma adrenocorticotropin (ACTH), serum cortisol
      and cytokine concentrations were observed on both the first and second days of
      the treatment. Subcutaneous administration of IFN significantly increased plasma
      ACTH and serum cortisol concentrations by 3 h after the injection. Serum
      interleukin-6 (IL-6) increased with the increase in circulating ACTH and
      cortisol. There was a significant correlation between serum cortisol and IL-6
      concentrations at 3 h. In contrast, an increase in serum interleukin-1 beta was
      only observed in one case. On the second day of IFN treatment, simultaneous
      administration of 25 mg diclofenac sodium eliminated the IFN effects on
      circulating ACTH, cortisol and IL-6 concentrations. The present studies
      demonstrated that circulating IL-6 increases after systemic IFN administration,
      resulting in activation of the pituitary-adrenal axis.

PMID- 8556064
TI  - A study of effect of CS-045, a new antidiabetic drug, on hypertension in
      spontaneously hypertensive rat.
AB  - Several lines of evidence have suggested that insulin resistance may play an
      important role in the pathogenesis of hypertension. CS-045 is a new hypoglycemic
      drug by which improves insulin sensitivity in peripheral tissues. We assessed the
      effect of CS-045 on hypertension in spontaneously hypertensive rats (SHR) and
      Wistar-Kyoto rats (WKY) as a control. At 20 weeks of age, the treatment with CS
      045 was started by being mixed with chow pellets in the proportion of 0.2% (w/w)
      and continued for 6 weeks. Nonfasting plasma glucose levels were not changed in
      either strain of rats treated with CS-045, but plasma insulin levels decreased in
      SHR 4 and 5 weeks after the start of CS-045 therapy. Blood pressure increased
      with age in SHR without treatment, but CS-045 decreased blood pressure only 4 and
      6 weeks after the treatment. These findings suggest that insulin resistance is
      not strongly associated with the pathogenesis of hypertension in SHR.

PMID- 8556065
TI  - Secretion of insulin and glucagon by the perfused pancreas of genetically obese
      (fa/fa) Zucker rats and its alteration with aging.
AB  - To evaluate the sequential changes in secretion of insulin and glucagon by the
      pancreas of Zucker fa/fa rats, we examined the secretion of these peptides by the
      perfused pancreas of the rats and by that of their lean littermates aged 9, 18,
      and 54 wks. Obese rats weighted significantly more than lean rats at all ages and
      had increased plasma insulin except for those at 54 wks of age. Isolated pancreas
      of obese rats at 9 wks showed greater insulin secretion response to glucose and
      arginine than that of lean rats at the same age. Insulin secretion response to
      arginine from pancreas of obese rats at 18 wks was also greater than that from
      pancreas of lean rats at 18 wks. Increased glucose concentration in the perfusion
      medium caused less suppression in obese rats than in lean rats. 10 mM arginine
      stimulation resulted in a higher secretion response in lean rats than in obese
      rats at 18 and 54 wks. Impairment of glucagon secretion was observed even at 54
      wks of age, when the obese rats no longer had significantly increased plasma
      insulin. This suggested that abnormal glucagon secretion was due not only to
      hyperinsulinemia, but also to a possible defect in the secretory mechanism.

PMID- 8556066
TI  - Proteolytic activity of IGFBP-3 in various clinical conditions during childhood
      studied by means of western immunoblotting.
AB  - Insulin-like growth factors (IGFs) have 6 types of binding proteins (IGFBPs), and
      IGFBP-3 is the major IGFBP in human sera. A proteolytic enzyme for IGFBP-3 has
      recently been reported to be present in human and animal pregnant sera. Although
      the physiological significance of a pregnancy-associated IGFBP-3 protease remains
      to be established, the proteolysis could result in lowering the affinity for
      IGFs, thereby enhancing their delivery to target tissues by increasing free IGFs
      in the circulation. The methods for detection of IGFBP-3 protease which have been
      widely used so far are a method reported by Lamson et al. which used affinity
      crosslinking or western ligand blotting. These methods need radioactive materials
      (iodinated IGFs and IGFBP-3) and it takes at least a few days to get the results.
      We have now developed a simple assay for the proteolysis of IGFBP-3. The method
      is western immunoblotting without radioactive materials. The results can be
      obtained in a day. With this method, we proved the absence of significant
      proteolytic activity in sera from rapidly growing children (early stage of
      puberty or precocious puberty), and sera from a severe type of growth hormone
      deficiency. Significant proteolytic activity, as in pregnant women, was detected
      in 6 out of 11 patients with acute disorders such as measles, Kawasaki disease,
      bacterial meningitis and mycoplasma pneumonia, some of whom were probably in a
      catabolic condition. These data suggests that the proteolysis of IGFBP-3 might
      also be important in modulating IGF action in some acute diseases during
      childhood. The increased bioavailability of IGFs by IGFBP-3 proteolysis may play
      a role in overcoming catabolic conditions.

PMID- 8556067
TI  - Decreased immunoreactive inhibin and increased FSH levels in cryptorchidism after
      orchidopexy.
AB  - The blood FSH level is often high in patients with severe testicular disorders
      including cryptorchids. To examine whether inhibin is involved in the increase in
      FSH we measured immunoreactive inhibin, FSH, LH, and testosterone in 17 patients
      after orchidopexy. FSH was extremely high (20 mIU/ml or above) in 3 patients. The
      inhibin level was significantly lower (P < 0.01) in these 3 patients (6.47 +/-
      2.19 IU/ml; mean +/- SEM) than in the other 14 patients (14.31 +/- 3.96 IU/ml).
      All 3 high-FSH patients had azoospermia. Testosterone and LH were normal in one
      of them. Even considering problems involved in the inhibin assay, the high FSH
      levels are considered to reflect reductions in the blood inhibin level due to
      Sertoli cell dysfunction. These findings suggest that inhibin plays an important
      role in the suppression of FSH at least in some patients after orchidopexy.

PMID- 8556068
TI  - Normal growth and pubertal development during bromocriptine therapy in two
      patients with prolactinoma.
AB  - The cases of two boys, a 14 years 10 months old and an 18-year-old, with delayed
      puberty are presented. The first patient also had a short stature. Both patients
      had a pituitary adenoma, as shown by computed tomography, with high prolactin
      levels. After bromocriptine therapy was started, there was a spontaneous
      progression of normal puberty. The first patient used a synthetic growth hormone
      together with bromocriptine, however, even after the growth hormone was stopped
      progression in puberty and gain in height continued. The favorable response
      obtained in these patients implies that bromocriptine can be an effective therapy
      for adolescent patients with prolactinoma.

PMID- 8556069
TI  - [Control of the menstrual cycle and ovulation].

PMID- 8556070
TI  - [Intra-uterine artificial insemination: what indications and which technics
      should be retained?].

PMID- 8556071
TI  - [Evaluation of hyperandrogenism: what levels?].

PMID- 8556072
TI  - [Cellular and molecular pathogenesis of cancer of the cervix].
AB  - There is now substantial evidence that specific human papillomavirus (HPV) types
      are probably an etiological factor of cervical cancer and its precursors. Virus
      infection, viral genes expression emerge as necessary but not sufficient for the
      cells transformation. The E6-E7 oncoproteins of "high risk" (HPV 16-18)
      papillomaviruses bind specifically, and with high affinity, to cellular tumor
      suppressor gene products p53 and pRb, in contrast to "low risk" (HPV 6-11) types.
      This bond disturbs the cell cycle and results in chromosomal instability,
      aneuploidy and is the probably starting point of the integration of viral DNA to
      the host genome. These endogenous modifications are reported to the morphological
      and colposcopical events of cervical intraepithelial neoplasia and seem to be
      most important in the pathogenesis of cervical cancer precursors lesions and
      tumor progression.

PMID- 8556073
TI  - [Complete hysterectomy for benign pathology and laparoscopy: respective
      indications of laparoscopic preparation and an exclusively laparoscopic
      approach].
AB  - According to whether uterine artery treatment takes place vaginally or
      laparoscopically, laparoscopy for hysterectomy can be considered according to two
      modalities: laparoscopically assisted vaginal hysterectomy (LAVH) and total
      laparoscopic hysterectomy (TLH). The indications for laparoscopy are defined by
      the limits and/or contraindications of the vaginal route. LAVH is indicated in
      the following situations: pelvic pain syndrome where diagnosis and treatment can
      be made at the same time as hysterectomy; minimal endometriosis; past surgical
      history favouring adhesions formation; necessity to perform an oophorectomy;
      existence of an ovarian pathology. The elective indications for TLH are the
      severe pelvic adhesions, deep endometriosis and especially a limited vaginal
      accessibility associating with a narrow vagina and a fixed or non prolapsed
      uterus. Laparoscopy thus allows to reduce the number of laparotomies. When on
      overage three quarters of the hysterectomies (excluding cases of uterogenital
      prolapse) were up till now performed abdominally, laparoscopy could reduce this
      rate to approximately 10%.

PMID- 8556074
TI  - [Laparoscopic tubal sterilization reversal: a technic using a single stitch].
AB  - We report our laparoscopic technique of tubal sterilization reversal. We perform
      a simple and atraumatic technique with a single point. After preparation and
      approximation of the two tubal segments, the anastomosis consists of one single
      suture placed at the "12 o'clock" site of the antimesenteric border. The
      feasibility, the advantages and the preliminary results are presented.

PMID- 8556075
TI  - [The role of ultrasonic endoscopy in the examination of post-obstetrical anal
      incontinence].
AB  - Echoendoscopy provides a means of exploring the anorectal and neighbouring areas.
      The technique has been used for over 10 years in cancerology and more recently in
      proctology. It can be used to confirm the anatomic integrity of the anal
      sphincters or to identify and localize damage, making it particularly interesting
      for the exploration of anal incontinence. Echoendoscopy has been used in several
      recent series which demonstrated that besides stretch neuropathies, defects in
      the sphincter play a role in post-obstetrical incontinence. Whether the signs
      occur early or late after menopause, these ruptures are easily identified with
      echoendoscopy. Thus, a reliable diagnostic of the anal lesion is possible before
      any therapeutic decision, not only for anal incontinence but also for prolapsus
      or urinary incontinence. Further prospective studies should confirm the
      contribution of echoendoscopy in deciding on surgical repair and help determine,
      and thus to prevent, the risk of sphincter rupture.

PMID- 8556076
TI  - [Monozygotic triplet pregnancy after transfer of frozen embryos].
AB  - We report a case of monozygotic triplet pregnancy after transfer of 3 frozen
      thawed embryos. The pregnancy ended by the birth of 3 healthy normal boys and all
      the analysis showed that it was really a monochorionic triamniotic triplet
      pregnancy, that as far as we know is the first reported one induced by frozen
      thawed technics. We shall discuss: the etiology of monozygotic pregnancies after
      IVF; the sonographic diagnosis of placentation; the obstetrical care which
      allowed the birth of 3 healthy normal boys.

PMID- 8556077
TI  - [The history of sterility in Antiquity. III. The anatomy and physiology of
      conception in the work of Soranos of Ephesus].
AB  - Soranos was highly regarded as the first and the most famous gynecologist in the
      antiquity. In point of fact, Soranos was not really a gynecologist but, he was
      the first to write a treatise about "gynecology". This work came down to us
      incomplete. In this study we analyse the conception's theories of Soranos.

PMID- 8556078
TI  - [A randomized, controlled trial comparing follicle stimulating hormone (FSH) to
      human menopausal gonadotropin (hMG) in fertilization in vitro].
AB  - The adverse effect of raised luteinizing hormone (LH) concentrations on
      reproductive outcome suggests that exogenous LH administration for ovarian
      stimulation may not be desirable. The aim of this study was to compare the
      clinical pregnancy rates between follicle stimulating hormone (FSH) and human
      menopausal gonadotrophin (HMG) used in in-vitro fertilization (IVF) cycles. A
      total of 232 infertile patients, with a mean duration of infertility of 67.1 +/-
      32.9 months, were selected for IVF (female age < 38 years, FSH < 15 IU/l, and
      total motile sperm count > 5 x 10(6). A short (flare-up) protocol with daily
      leuprolide acetate was followed randomly from day 3 with FSH (n = 115) or human
      menopausal gonadotrophin (HMG; n = 117), at an initial dose of two ampoules per
      day. A maximum of three embryos was transferred, and the luteal phase was
      supported with four doses of HCG (2,500 IU). No differences were observed between
      the two groups in any of the cycle response variables except fertilization rates
      per oocyte and per patient, both of which were significantly higher with FSH.
      Clinical pregnancy rates per cycle initiated, per oocyte retrieval and per embryo
      transfer were 19.1, 21.0 and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4%
      respectively for HMG. Whilst these differences were not statistically
      significant, the results of this interim analysis suggest that HMG may be
      associated with a lower clinical pregnancy rate than FSH.

PMID- 8556080
TI  - Alternative therapies.

PMID- 8556079
TI  - Tubulin aggregates induced by Ni2+ present microtubular characteristics.
AB  - Rat brain tubulin in a proper buffered solution became insoluble in the presence
      of 10 mM NiCl2, and sedimented at centrifugal forces as low as 500 x g for 30
      min. Both nickel-sedimented and microtubular tubulin conserved 65% of colchicine
      binding activity after 25 days of storage at -20 degrees C. However in brain
      cytosol, only 9% of the initial binding activity was conserved. The
      electrophoretic mobility of tubulin recovered from aggregates also remained
      unaltered. Therefore the aggregates formed with Ni2+ share important
      physicochemical properties with microtubules.

PMID- 8556081
TI  - Chest tube removal practices in critical care units in the United States.
AB  - BACKGROUND: Pain assessment and management are recognized as major problems in
      critical care settings. However, little is known about pain management practices
      related to medical procedures performed in the ICU, particularly removal of chest
      tubes. OBJECTIVES: To describe practices related to chest tube removal in the
      United States, with an emphasis on pain assessment and management. METHODS: A
      survey instrument was developed and mailed to 995 members of the American
      Association of Critical-Care Nurses who cared for patients with chest tubes. They
      were asked about chest tube removal practices in their institutions. RESULTS:
      Chest tubes are removed primarily by physicians and house staff, although 11% of
      respondents reported that specially trained nurses removed the tubes. Only 16%
      indicated that a prescription for pain medication was routinely available before
      chest tube removal. The drug administered most frequently was intravenous
      morphine sulfate, but the dose varied considerably. Nurses were generally
      satisfied (65.6%) with practices related to chest tube removal in their unit;
      nurses who were not satisfied (34.4%) wished to see better pain management
      practices (45%), removal of tubes by the patient's assigned nurse (17.8%), a
      protocol for tube removal (13.9%), notification of the nurse before removal
      (12.2%), and other changes (10%). CONCLUSIONS: Practices associated with chest
      tube removal, especially pharmacologic management of procedure-related pain, vary
      in critical care units. Caregivers are advised to develop practice policies to
      guide decisions about management of acute pain in this patient population.

PMID- 8556082
TI  - Moisture chamber versus lubrication for the prevention of corneal epithelial
      breakdown.
AB  - BACKGROUND: Patients who are comatose or semicomatose are at risk of corneal
      dryness and ulceration. OBJECTIVE: To compare and evaluate the effectiveness of
      two treatments used for the prevention of corneal epithelial breakdown in
      critically ill patients. METHODS: A randomized clinical trial was used. The
      sample consisted of critically ill patients (age, 15-84 years) with a limited or
      absent blink reflex in a 14-bed general intensive care unit in a large
      metropolitan teaching hospital. Ninety-six eligible patients were studied; of
      these, 36 were excluded and data from the remaining 60 patients were analyzed.
      Patients were randomized to receive methylcellulose lubricating drops every 2
      hours (n = 30) or to have their eyes covered with a polyethylene film to create a
      moisture chamber (n = 30). The patients' corneas were tested daily for epithelial
      breakdown using fluorescein drops. Patients were studied for a minimum of 48
      hours and a maximum of 1 week. RESULTS: Eight of the 30 patients in the
      lubricating drop group had positive fluorescein staining, compared with one in
      the moisture chamber group. CONCLUSION: Our results suggest that a moisture
      chamber is more effective than lubricating drops in preventing corneal epithelial
      breakdown in critically ill patients with limited or absent blink reflex.

PMID- 8556083
TI  - Current nursing practice of point-of-care laboratory diagnostic testing in
      critical care units.
AB  - BACKGROUND: The development of user-friendly laboratory analyzers, combined with
      the need for rapid assessment of critically ill patients, has led to the
      performance of in vitro diagnostic testing at the point of care by personnel
      without formal laboratory training. OBJECTIVES: To determine the range of
      laboratory testing performed by critical care nurses and their attitudes toward
      this role. METHODS: A survey of critical care nursing consultants was conducted,
      using a modified Likert scale, to assess objective measures of point-of-care
      testing practice in critical care units and to determine nurses' attitudes toward
      the practice of point-of-care testing. Statistical analysis was performed to
      determine significant trends in responses. RESULTS: Of the units responding to
      the survey, 35% used critical care nurses exclusively to perform point-of-care
      testing, 32.5% used laboratory technicians and critical care nurses, and 25% used
      other personnel. Of critical care nurses performing laboratory testing, 95.5%
      performed blood glucose analysis; 18.7%, arterial blood gas analysis; 4.5%,
      electrolyte analysis; 4.5%, hematology profiles; and 22.7%, other testing. Most
      agreed that stat tests were not reported promptly, thereby necessitating bedside
      testing. Respondents indicated that they would prefer that laboratory personnel
      operate in vitro diagnostic equipment and that requirements for critical care
      nurses to perform laboratory testing detracted from other patient care duties.
      CONCLUSIONS: Most nurses who perform point-of-care testing responded that it was
      necessary and helpful in patient management. However, they would prefer, because
      of their other patient care responsibilities, that laboratory personnel take this
      responsibility.

PMID- 8556084
TI  - Analgesic administration, pain intensity, and patient satisfaction in cardiac
      surgical patients.
AB  - BACKGROUND: Pain can adversely affect a patient's physiological and psychological
      recovery, yet little is known about the pain experience of cardiac surgical
      patients. OBJECTIVES: To examine nursing practice regarding analgesic
      administration and measure pain intensity and patient satisfaction with pain
      management practices. METHODS: To establish baseline nursing practice regarding
      analgesic administration, charts were reviewed retrospectively in 50 adult
      cardiac surgical patients, and the same information was collected concurrently
      for a prospective sample of 51 patients. The subjects completed visual analogue
      scales as a measure of pain intensity twice daily while in the cardiothoracic
      intensive care unit and Pain Relief Satisfaction Questionnaires on the day after
      transfer from the unit. RESULTS: Patients in the prospective group received
      significantly more analgesia. Pain intensity was moderate (4 or greater on the
      Visual Analogue Scale). Women had higher overall visual analogue scale scores
      than did men, 4.57 versus 3.70. Patients in whom an internal mammary artery had
      been used as a bypass graft had significantly higher scores compared with
      patients with vein grafts. The Pain Relief Satisfaction Questionnaire responses
      indicated that 96% of the patients experienced effective pain management in the
      cardiothoracic intensive care unit. CONCLUSIONS: Despite receiving analgesic
      doses twice those reported elsewhere for similar populations, the patients in
      this study reported moderate pain intensity. This finding was confounded by the
      fact that 96% expressed satisfaction with their pain management in the
      cardiothoracic intensive care unit. Frequent assessment and documentation of both
      pain and pain relief from interventions are necessary if the healthcare team is
      to implement an individualized analgesic regimen.

PMID- 8556085
TI  - Nitric oxide inhalation in infants and children: physiologic and clinical
      implications.
AB  - Nitric oxide is a significant biologic mediator in a number of physiologic
      processes. Clinical and laboratory studies in both human and animal models have
      uncovered a number of conditions responsive to nitric oxide therapy. The use of
      inhaled nitric oxide is rapidly expanding into neonatal and pediatric critical
      care. Presently, the primary clinical indication for nitric oxide is pulmonary
      hypertension of either a primary or secondary etiology. Some patient populations
      that are refractory to conventional management demonstrate significant
      improvement when receiving nitric oxide therapy. This article discusses the
      physiologic properties of nitric oxide, as well as its diagnostic and therapeutic
      indications. Specific issues regarding nitric oxide delivery, monitoring, safety
      standards, and nursing care are also addressed.

PMID- 8556086
TI  - Physiologic response to two endotracheal suctioning techniques in newborn lambs
      with and without acute pulmonary hypertension.
AB  - BACKGROUND: Endotracheal suctioning may cause sudden increases in pulmonary
      arterial pressure, which can result in hypoxia secondary to right ventricular
      failure and/or increased right-to-left shunting. An adaptor that allows
      suctioning without disconnecting the ventilator has been proposed to prevent
      these problems; however, its efficacy has not been rigorously studied. OBJECTIVE:
      To examine the physiologic responses to two endotracheal suctioning techniques in
      newborn lambs with and without acute pulmonary hypertension. METHODS: A repeated
      measures design was used to compare two endotracheal suctioning techniques in
      seven newborn lambs with and without acute pulmonary hypertension. An adaptor was
      used in the ventilator-controlled technique, making disconnection of the
      ventilator during suctioning unnecessary. In the bag-controlled technique, the
      ventilator was disconnected and ventilation was done with a manual resuscitation
      bag. Physiologic variables, pulmonary and mean arterial pressure, peak
      inspiratory pressure, mixed venous oxygen saturation, cardiac index, and arterial
      blood gas values were recorded before, during, and after endotracheal suctioning.
      RESULTS: Endotracheal suctioning caused a statistically significant systemic
      hypertensive response in lambs with and without acute pulmonary hypertension,
      regardless of which suctioning technique was used. No statistically significant
      changes occurred in pulmonary arterial pressure using either technique.
      CONCLUSIONS: Use of an adaptor resulted in no differences in the physiologic
      responses to endotracheal suctioning. However, endotracheal suctioning was easier
      to perform using an adaptor because no extra equipment or person was needed.

PMID- 8556087
TI  - Comparison of continuous with intermittent bolus thermodilution cardiac output
      measurements.
AB  - BACKGROUND: Few complete studies have been published to validate the agreement
      between continuous cardiac output and intermittent thermodilution cardiac output.
      OBJECTIVE: To analyze the agreement between cardiac output measurements by the
      continuous thermodilution method and the intermittent bolus thermodilution
      method, using a continuous cardiac output catheter in postoperative
      cardiothoracic surgery patients. METHODS: A convenience sample of 14 adult
      cardiothoracic surgical patients with thermodilution pulmonary artery catheters
      placed preoperatively was used. A total of 214 comparison measurements of cardiac
      output by both the continuous and intermittent thermodilution methods were taken
      on patient admission to the critical care unit, every 4 hours, and with any
      change greater than 10% from baseline readings. RESULTS: The intraclass
      correlation between continuous cardiac output and intermittent cardiac output was
      .89. The limits of agreement were -1.34 to 1.18 L/min, indicating that in 95% of
      readings the difference between continuous cardiac output and intermittent
      cardiac output were within this range. CONCLUSIONS: The continuous cardiac output
      monitoring method shows clinically acceptable agreement with the intermittent
      cardiac output method.

PMID- 8556088
TI  - Frequency requirements for zeroing transducers in hemodynamic monitoring.
AB  - BACKGROUND: Accurate hemodynamic monitoring information can be obtained only if
      the transducer/amplifier system is used correctly. One major component of correct
      use is zeroing the transducer to provide a relative reference point on which to
      measure hemodynamic pressures. However, nursing requirements for frequency of
      zeroing are inconsistent. In addition, the concepts of leveling and zeroing are
      frequently confused. OBJECTIVE: To determine whether transducers drift from zero
      (+/- 2 mm Hg), and if they do not drift from zero, how long they hold a zero
      value. METHODS: The study, conducted in four midwestern hospitals, was carried
      out in two parts: an initial 10-day bench test of 50 transducers and an
      evaluation of 388 transducers attached to patients for 1 to 5 days. Transducers
      were monitored over time after being consistently leveled. RESULTS: Bench testing
      indicated that 100% of transducers did not drift +/- 2 mm Hg from zero during the
      study period. In the clinical study, only 1.3% of transducers drifted from zero.
      Five transducers drifted +/- 2 mm Hg from zero, with a range of -5 to 3 mm Hg.
      CONCLUSIONS: We conclude that transducers used for hemodynamic monitoring require
      zeroing only on initial setup and disconnection from the amplifier.

PMID- 8556089
TI  - Endovascular stented graft repair of a pseudoaneurysm of the subclavian artery
      caused by percutaneous internal jugular vein cannulation: case report.
AB  - In high-risk patients endovascular repair of a pseudoaneurysm with a stented
      graft is a safe and reasonable treatment option that can preclude significant
      morbidity and shorten hospital stay. We report a case of pseudoaneurysm of the
      subclavian artery after internal jugular vein cannulation that was treated
      successfully with an endovascularly inserted, stented graft. The case report
      highlights the importance of recognizing this unusual but serious complication of
      percutaneous internal jugular vein catheterization through careful clinical
      examination, prompt duplex scanning, and arteriography.

PMID- 8556090
TI  - Defining and redefining death.
AB  - The definition of death, brain death in particular, is increasingly important to
      critical care professionals. There are essentially three definitions of death
      from a theoretical perspective: the traditional heart-lung definition, the whole
      brain definition, and the higher-brain definition. These definitions use
      different underlying assumptions within their own theoretical framework. The
      differing definitions and theoretical frameworks have encouraged physiological,
      philosophical, spiritual, and ethical analyses, which have led to spirited debate
      throughout the healthcare community and especially in critical care.

PMID- 8556091
TI  - Regression of coronary artery disease: the role of plaque biology.
AB  - Research has lead to a better understanding of the pathophysiology and history of
      atherosclerotic heart disease, which has reached epidemic proportions in
      industrialized countries in this century. Atherosclerosis should be seen as a
      chronic, protracted process that encompasses complex and dynamic interactions
      between cellular, biochemical, and biophysical factors in the microcosmos of the
      arterial vessel wall and blood circulation. In this context, the ultimate
      consequences of this disease process, namely coronary artery disease, must be
      seen as the "tip of the iceberg." The most dramatic manifestation of coronary
      artery disease, the acute coronary syndrome, usually occurs as the result of
      different forces and factors, which lead to abrupt plaque disruption, rupture,
      and vessel thrombosis. In contrast, the genesis of this atherosclerotic lesion is
      a slow process. Despite considerable experimental clinical evidence accrued
      during the past decade, atherosclerosis remains a complex pathophysiological
      process that is not fully understood. It is clear, however, that the interaction
      between the cellular elements of the vessel wall and the circulation are the
      determinants of atheroma formation. In this regard, the vascular endothelium
      appears to play a pivotal role because of its strategic location and metabolic
      activity. Antilipidemic therapy influences the outcome of coronary disease
      through a variety of mechanisms, including direct and indirect effects on the
      endothelium.

PMID- 8556092
TI  - Lithium therapy: limitations and alternatives in the treatment of bipolar
      disorders.
AB  - As clinical experience with lithium treatment of bipolar disorders accumulates,
      factors predictive of nonresponse are emerging. Prominent among these are
      conditions such as comorbid substance abuse and the presence of the malignant
      variants rapid cycling and mixed states. Lithium therapy is further complicated
      by noncompliance, attributable in large measure to burdensome side effects such
      as memory impairment and cognitive slowing. The issues of lithium nonresponse and
      noncompliance have driven the search for alternative agents, such as the
      anticonvulsants carbamazepine and valproic acid. While preliminary evidence
      suggests that these agents may provide improvements over lithium in terms of
      tolerability and response (especially in rapid cycling and mixed states),
      methodologic limitations temper the conclusiveness of these findings. The natural
      history of bipolar disorders is defined by characteristic symptom clusters which
      evolve in intensity and duration over long time scales, resulting in a high
      morbidity and mortality. These features raise critical concerns for research
      design, especially concerning the ethics of placebo controls and the need to
      generate long-term observational data upon which to predicate meaningful
      treatment recommendations. With the apparent increase in lithium nonresponse in
      recent years, the need to identify and definitively evaluate alternative agents
      is becoming imperative.

PMID- 8556093
TI  - Affective comorbidity in children and adolescents with attention deficit
      hyperactivity disorder.
AB  - Recent research examining comorbidity associated with attention deficit
      hyperactivity disorder (ADHD) has raised the possibility of the existence of
      subtypes of the disorder. If this is the case, delineating subgroups is
      clinically imperative. Two hundred seventy nonrepetitive, consecutively admitted
      children and adolescent inpatients received structured diagnostic interviews
      (Schedule for Affective Disorders and Schizophrenia in School Aged Children).
      Twenty-eight percent of these children met the criteria for ADHD. Of those
      children with an ADHD diagnosis, 68% also met the criteria for an affective
      disorder. Thirty-six percent met the full criteria for major depression disorder.
      Eight percent met the criteria for an affective psychosis and 22% were diagnosed
      with bipolar disorder. There was a significant overlap between ADHD and bipolar
      disorder, suggesting the possibility of a lack of specificity in the diagnostic
      instruments used in this population. The results support the clinical necessity
      of carefully assessing for occult affective illness in all children and
      adolescents with attention deficit disorder.

PMID- 8556094
TI  - An epidemiologic study of prn/stat medication use in a state psychiatric
      hospital.
AB  - The prevalence of prn/stat psychotropic medication administration and the
      characteristics and concomitants of high use of these medications were examined
      via a retrospective medical record review in a 973-bed state hospital. While
      22.9% of the total hospital population received at least 1 prn/stat dose during
      the study month, 27 patients (2.8% of the total population) received 44.4% of the
      prn/stat doses, averaging 9.7 doses per patient. Examination of high-prn/stat use
      patients whose disruptive behavior and prn/stat use was "intermittent" throughout
      the month (N = 16) vs those who exhibited these characteristic for only a
      "discrete period" with resolution (N = 11) suggested that the prescription of
      antipsychotic drugs as prn/stat doses as well as increases in or institution of
      these medications was significantly associated with the latter group's resolution
      of disruptive behavior. The findings suggest the need for clinical protocols as
      guides for clinicians in the establishment of effective pharmacotherapy for
      patients with agitated, threatening behavior, including the use of plasma levels
      to ensure adequate dosage of psychotropic medication.

PMID- 8556095
TI  - Complaints of constipation in obsessive-compulsive disorder.
AB  - Psychoanalytic observation has launched a long tradition in medical literature
      that links constipation with obsessive-compulsive traits. This association,
      however, has never been tested empirically. The current investigation sought to
      test this hypothesized association empirically using a large, randomly sampled
      population database. Data from the Epidemiologic Catchment Area project collected
      with the Diagnostic Interview Schedule were analyzed to determine the
      association, if any, of complaint of medically unexplained constipation
      (ascertained from the somatization disorder section of the interview) with a DIS
      diagnosis of obsessive compulsive disorder (OCD). Reported history of
      constipation was significantly associated with a lifetime diagnosis of OCD in
      women (not men), even when controlling for symptom-reporting biases using number
      of other positive somatoform symptoms. This association was specific to
      constipation and OCD and did not apply to other functional bowel symptoms
      including diarrhea, bloating (gas), and abdominal pain. Other psychiatric
      disorders commonly implicated with functional bowel complaints--major depression
      and panic disorder--were not significantly associated with constipation
      controlling for effects of other somatoform symptoms. The lack of association of
      constipation with OCD in men in a general population sample fails to support
      psychoanalytic concepts that historically have linked these two phenomena, but a
      special relationship of OCD with constipation was present in women.

PMID- 8556096
TI  - Family psychiatric histories in male patients with generalized anxiety disorder
      and major depressive disorder.
AB  - It has been hypothesized, from twin study results in females, that the genetic
      predisposition in females for major depressive disorder (MDD) and generalized
      anxiety disorder (GAD) is identical. This report attempted to replicate these
      findings on a male population using family history methods. There were 119
      subjects who completed standardized assessment of Axis I, Axis II, and family
      history. The family history of four groups was compared--GAD without MDD, MDD
      without GAD, GAD/MDD, and normals. As expected, GAD and MDD subjects showed
      trends toward more MDD family history than normals. The GAD and MDD groups showed
      only trend differences in family history of relatives. Unexpectedly, however, the
      MDD/GAD group had no higher level of either anxiety or depressive family history
      than normals (although they did have higher levels of personality family
      history). Both the GAD and the MDD groups had a significantly higher level of
      family history of depression than the GAD/MDD group. Within the limits of the
      family history method, the finding of similarity of the family predisposition of
      MDD and GAD was confirmed in a male population. However, it does appear that the
      combined disorder of MDD/GAD in clinical settings might have very different
      family history predispositions and possibly could be a separate disorder from
      both MDD and GAD when they are not comorbid.

PMID- 8556097
TI  - A case-control study of rapid readmission in a state hospital population.
AB  - A case-control comparison of clinical and service system characteristics among
      chronic psychiatric patients with rapid readmission (within 90 days of
      discharge), patients with readmission after more than 90 days of community
      tenure, and nonreadmitted patients revealed several clinical variables (e.g.,
      medication noncompliance, substance abuse, and disruptive behavior) to be
      associated with readmission regardless of community tenure. In contrast, two
      service system variables (discharge to a structured outpatient treatment program
      and adequacy of discharge planning) were more highly associated with rapid
      readmission than the other conditions, while availability of case management had
      no association with readmission, rapid or otherwise.

PMID- 8556098
TI  - Medication treatment in first-admission patients with psychotic affective
      disorders: preliminary findings on research-facility diagnostic agreement and
      rehospitalization.
AB  - The discharge medications of 101 Suffolk County subjects with facility and/or
      research diagnoses of affective disorder were ascertained. Rehospitalization was
      recorded for a 6-month follow-up period. Twenty-three of 31 patients (74.2%) with
      a facility diagnosis of depressive disorder were prescribed antidepressants, and
      21 of 36 patients with a facility diagnosis of bipolar disorder (58.3%) were
      prescribed lithium. When research and facility diagnoses concurred, 84.2% of
      depressed patients were prescribed antidepressants, and 66.7% of bipolars were
      given lithium. The percentages were lower when the two diagnoses were discrepant.
      The results for diagnostic congruence were independent of demographic variables,
      length of stay, and premorbid functioning. Patients prescribed diagnosis-specific
      medications had a lower rate of rehospitalization (7.3%) than those not
      prescribed such medications (22.2%). The findings suggest that such medications
      are prescribed in the more unambiguous cases of affective disorders and are
      important (with or without antipsychotic treatment) in preventing
      rehospitalization.

PMID- 8556099
TI  - Neuroleptic malignant syndrome associated with clozapine treatment.
AB  - Although not universally accepted, evidence exists that clozapine treatment may
      be associated with neuroleptic malignant syndrome (NMS). To date, 10 cases of NMS
      associated with the use of clozapine have been reported in the literature. We
      report two more cases of NMS in patients on clozapine treatment and review the
      clinical presentations, biochemical features, risk factors, treatment, and
      rechallenge with neuroleptics in all reported patients who developed NMS while
      receiving clozapine treatment. An update and critical review of clozapine-induced
      NMS are also presented. Clozapine treatment can cause NMS similar to that induced
      by conventional neuroleptics. A history of NMS, existing brain insults, low serum
      iron concentrations, and being a young male may be risk factors for the
      development of NMS associated with clozapine treatment. NMS most commonly occurs
      when clozapine is being used along with other psychotropics. Early recognition of
      the syndrome and cessation of clozapine when NMS occurs are advised. Supportive
      care and use of dopamine agonists and dantrolene may be helpful in treating
      clozapine-associated NMS. These results support the notion that clozapine can
      cause NMS. However, NMS associated with clozapine treatment is a rare event. When
      it happens, the clinical presentation, risk factors, and management appear to be
      similar to those of NMS associated with conventional neuroleptics.

PMID- 8556100
TI  - Clozapine-caused eosinophilic colitis.
AB  - Four patients with diarrhea and eosinophilia associated with clozapine therapy
      are presented. In two cases clozapine therapy was interrupted but then restarted;
      all patients eventually tolerated clozapine well. A syndrome of clozapine-induced
      eosinophilic colitis is suggested.

PMID- 8556101
TI  - Bupropion and anticonvulsant drug interactions.
AB  - The use of bupropion (BUP) involves a higher seizure risk than the use of other
      antidepressants, limiting its dose and widespread use. The two reported cases
      document anticonvulsant-BUP drug interactions through plasma levels.
      Carbamazepine appeared to decrease the plasma BUP to nondetectable levels, while
      hydroxybupropion was found at very high levels. Data presented suggest that BUP
      may increase sodium valproate levels. Conclusions from these case reports are
      tentative, pending further study. Monitering of BUP and its metabolites may
      ultimately prove useful in guiding clinicians dosing decisions, especially when
      mood stabilizers are combined with other psychotropic drugs in refractory bipolar
      patients.

PMID- 8556102
TI  - Control of meningococcal disease: guidance for consultants in communicable
      disease control. PHLS Meningococcal Infections Working Group and Public Health
      Medicine Environmental Group.

PMID- 8556103
TI  - Control of meningococcal disease: guidance for microbiologists: CCDC. Consultant
      in Communicable Disease Control, England.

PMID- 8556104
TI  - Chemoprophylaxis fails to prevent a second case of meningococcal disease in a day
      nursery.

PMID- 8556105
TI  - Influenza surveillance in England and Wales: October 1994 to June 1995.
AB  - This report summarises the information obtained by surveillance of influenza in
      England and Wales from October 1994 to June 1995 (weeks 40/94 to 25/95).
      Influenza B viruses were responsible for most infections, with moderate activity
      occurring throughout the winter, peaking in February. Influenza A became more
      active towards the end of the winter, and laboratory reports reached a peak in
      May (week 21/95). Influenza activity was seen first in Wales, then England,
      followed by Scotland. An increase in 'total respiratory disease' was reported in
      December 1994 by the Birmingham Research Unit of the Royal College of General
      Practitioners (RCGP) in England and Wales. This was probably due largely to an
      increase in reports of acute bronchitis, and was concurrent with the annual
      increase in respiratory syncytial virus infection which is often associated with
      bronchiolitis. Circulating influenza viruses were antigenically similar to
      components of the vaccine chosen for 1994/95. This report summarises the
      recommendations for the 1995/96 influenza vaccine.

PMID- 8556106
TI  - Was a measles epidemic imminent?

PMID- 8556107
TI  - Effecting change in physician practice as health care systems consolidate.

PMID- 8556108
TI  - Developing and using a data repository for quality improvement: the genesis of
      IRIS.
AB  - BACKGROUND: In 1991 the Inova Health System, a regional hospital system in
      Fairfax, Virginia, started developing a patient data repository, the Inova
      Research Information System (IRIS), to support clinical quality improvement,
      managed care contracting, and technology assessment. BUILDING A DATABASE
      PROTOTYPE: The prototype was built with the help of five key early user groups;
      each group, led by an influential physician, was eager to have access to data
      important to their work in an integrated and standardized electronic format.
      USING THE DATABASE: IRIS serves as the principal resource that QI committees,
      risk managers, managed care contracting officers, and others turn to for data to
      support their studies of the processes of care used and patient outcomes.
      Clinicians should use data analysis to identify opportunities for QI and
      implement change in their processes of care as a result. IRIS has already been
      used to make selected comparisons of patient management. For example, at Inova's
      largest hospital, for patients with a primary diagnosis of acute myocardial
      infarction (but without any unrelated secondary diagnoses), the length of stay
      was significantly shorter (5.5 days) when the attending physician was a
      cardiologist rather than an internist (7.5 days) or family practitioner (7.7
      days). SUMMARY: IRIS represents an architecture of study of patients, clinicians,
      and administrators--and the outcomes and the results produced. By the end of 1995
      three years of integrated clinical and financial data on inpatients will be
      available, permitting creation of a feed-back loop for continuous clinical and
      managerial learning.

PMID- 8556109
TI  - Improving breastfeeding support: a community health improvement project.
AB  - BACKGROUND: Because of the brevity of the postpartum hospital stay, mothers and
      their newborns are discharged home before breastfeeding is well established. In
      1992, feedback from patients who had given birth at Fletcher Allen Health Care
      (Burlington, VT) suggested a need for more consistent, expert, and timely
      assistance with breastfeeding in the hospital and better continuity of care
      during the first few weeks at home. QUALITY IMPROVEMENT TEAM: In 1993 a team
      developed objectives, analyzed the problem and possible solutions, and made eight
      recommendations on how the hospital could do more to promote breastfeeding.
      Implementation by team members and hospital staff included policy development,
      staff education, acquisition of funding, a visiting professorship, development of
      a lactation consultant coordinator and team, and patient surveys to evaluate the
      program. A late 1994 survey of 63 postpartum patients on their day of discharge
      indicated a high level of satisfaction with breastfeeding support in the
      hospital. CURRENT STATUS: Activities are being undertaken for lactation
      consultation coverage, further policy development, implementation of nurse
      competency validation, improved patient and family education materials, and
      continued evaluation of the breastfeeding support program through patient
      surveys. CONCLUSION: In the face of barriers such as the project's large scope, a
      paucity of internal team members, and a large number and variety of
      recommendations, some of the recommendations and follow-up plans have yet to be
      implemented. Yet the project has yielded improvements in care and provides a
      model of how hospitals can expand their traditional boundaries of care and
      quality improvement into community health issues.

PMID- 8556110
TI  - CQI action team: responding to the detoxification patient.
AB  - BACKGROUND: The management of detoxification patients is a complex
      interdisciplinary effort requiring involvement, cooperation, and understanding
      from staff at all levels of the facility. In 1992-93, alcohol-related diagnoses
      were the highest admission diagnosis at the Royal C. Johnson Veterans Affairs
      Medical Center (VAMC). Yet only 44% of the detoxification patients admitted to
      the VAMC were placed in beds specifically designed for detoxification. Initially,
      the action team believed that the issues were apparent and that the problems were
      the result of uncooperative and noncompliant providers who were not following
      established policy. METHODS AND RESULTS: Data analysis of admission and discharge
      trends, laboratory results, and bed census revealed discrepancies with several
      widespread myths held by local health care workers. These misperceptions and
      attitudes often interfered with treatment. CONCLUSIONS: Recommended changes
      included the development of a clinical pathway for the detoxification patient,
      implementation of an alcohol withdrawal assessment tool to manage and treat the
      patient at risk for experiencing alcohol withdrawal, and hospitalwide education
      on management of the detoxification patient.

PMID- 8556112
TI  - Red man syndrome and the red button system: where next for inpatient adverse drug
      reaction reporting?

PMID- 8556111
TI  - The incident reporting system does not detect adverse drug events: a problem for
      quality improvement.
AB  - OBJECTIVES: The objectives of this study were 1) to determine the frequency with
      which adverse drug events result in an incident report (IR) in hospitalized
      patients; and 2) to determine if there were differences between quality assurance
      administrators, nurse leaders in quality assurance, and staff nurses as to
      whether an incident report should or would be filed for each adverse drug event.
      STUDY DESIGN: All patients admitted to five patient care units (one medical
      intensive care unit, two surgical intensive care units, and two medical general
      care units) in one academic tertiary care hospital were studied between February
      and July 1993. The main outcome measures used were adverse drug events (ADEs) and
      IRs. Consensus voting was used by senior hospital administrators, nursing
      leaders, and staff nurses to determine whether an adverse drug event should have
      been reported and would have been reported. RESULTS: Of 54 adverse drug events
      identified by the study, only 3 patients (6%) had a corresponding incident report
      submitted to the hospital's quality assurance program or called into the pharmacy
      hotline. One additional ADE was identified by an IR, but not by the ADE study. Of
      the 55 ADEs, 15 were preventable, and 26 were serious or life-threatening, yet
      only 2 of the 26 led to an incident report. The three voting groups agreed that
      most ADEs justified an IR, but judged that in actual practice, an IR would
      infrequently have been filed. CONCLUSIONS: Voluntary reporting identified only a
      small fraction of ADEs. Using IRs for quality assurance/quality improvement will
      lead to significant bias when assessing quality of care.

PMID- 8556113
TI  - The future of outcomes research may benefit from the evolution of medical
      critical thinking.

PMID- 8556114
TI  - From incremental improvement to Breakthrough Thinking: an interview with David
      Ralston. Interview by Steven Berman.

PMID- 8556115
TI  - The pediatrician, sports medicine, and managed care.

PMID- 8556116
TI  - Inadequate history as a barrier to immunization.
AB  - OBJECTIVES: To evaluate how lack of immunization history contributes to missed
      opportunities for immunization and to document the effort required to obtain
      immunization history. DESIGN: Cross-sectional. SETTING: Urban, inner-city primary
      care pediatric clinic serving a low-income, multiethnic population. PATIENTS:
      Ninety-five new patients seen for either well-child care (53 patients) or acute
      illnesses (42 patients) during a 4-month period in 1993. Fifty-nine patients were
      aged 3 to 59 months and 36 were aged 5 to 15 years. MEASUREMENTS: Efforts to
      obtain immunization history were documented by means of a standardized data
      collection form. RESULTS: Immunization history was obtained for only 26 (27%) of
      95 patients during the initial visit. Caregivers of 74 (78%) of 95 patients did
      not bring immunization records to the initial visit; they were no more likely to
      bring records for well-child care than for acute care or for younger vs older
      children. Parents brought immunization records more often than did nonparents. A
      total of 145 telephone calls were made and 30 letters were sent in an attempt to
      obtain immunization histories. Immunization records were never found for 10 new
      patients (11%). Thirty-two patients (34%) were found to be lacking immunizations.
      Of these, only three patients had contraindications to immunization at the
      initial visit. Therefore, in one third of our new patients, opportunities to
      immunize were missed solely because their immunization records were unavailable
      at the initial visit. In another one third of cases, caregivers had incorrectly
      believed their child's immunizations to be up to date. CONCLUSIONS: Opportunities
      to immunize children were often missed because of a lack of immunization history.
      Our experience supports the need for improved documentation of immunization
      histories.

PMID- 8556117
TI  - Fair-play rules and injury reduction in ice hockey.
AB  - OBJECTIVE: To determine the rate, type, and severity of injuries incurred and
      penalties assessed during the qualifying fair-play (points for playing without
      excessive penalties) and championship "regular" rules (winner advances) portions
      of a 1994 Junior Gold ice hockey tournament. DESIGN: A prospective evaluation of
      injuries by certified athletic trainers at the tournament site. SETTING: A
      community-organized, 3-day, 31-game tournament in Minnesota. PARTICIPANTS: Two
      hundred seventy-three male players, younger than 20 years and in high school.
      MEASUREMENTS/MAIN RESULTS: Injuries were recorded by an on-site certified
      athletic trainer, and the penalties were tallied from the score sheets. The
      injury rates for the total number of injuries were 26.4 injuries per 1000 athlete
      exposures and 273.8 injuries per 1000 player hours. When only notable injuries
      (concussion, facial laceration, or moderate level of severity and above) were
      considered, the injury rates were 10 per 1000 athlete exposures and 103.9 per
      1000 player hours. The ratio of notable fair-play to notable regular-rules
      injuries was 1:4.8. The number of penalties assessed per game averaged 7.1
      penalties during fair-play rules and 13 penalties during the regular-rules
      competition. Penalties related to rough play and injury occurred four times more
      frequently during games with regular rules than those with fair-play rules.
      CONCLUSIONS: The fair-play concept can reduce injury rates, penalty rates, and
      severity of penalties and should be considered for ice hockey at all levels of
      play. The fair-play concept could be applied to other contact sports to reduce
      injury rates and rules infractions.

PMID- 8556118
TI  - Association between child behavior problems and frequent physician visits.
AB  - OBJECTIVE: To determine the association between parent-reported behavior problems
      and health care utilization, especially among physically healthy children.
      DESIGN: Analysis of data from the 1988 National Health Interviews Survey--Child
      Health Supplement. The sample for analysis consisted of 11,840 children aged 5 to
      17 years. The independent measure of primary interest are behavior problems as
      measured by the Behavior Problems Index. For the bivariate analysis, children in
      the lowest quartile, highest quartile and middle half were compared. For the
      multivariate analysis, children in the highest quartile with behavior problems
      were compared with all other children. MAIN OUTCOME MEASURES: The number of
      reported physician visits in the past year and the past 2 weeks, Two common
      behavior syndromes--antisocial and depressed or anxious--were analyzed separately
      to determine whether a specific type of behavior problem was associated with
      frequent health care utilization. RESULTS: Eighteen percent of the children aged
      5 to 17 years had four or more health visits during the past year, and 2% had two
      or more visits during the past 2 weeks. Children in the top quartile for parent
      reported behavior problems were more likely to have four or more physician visits
      than children in the middle half and bottom quartile. Children reported to be in
      "excellent," "very good," or "good" health who were in the top quartile of
      behavior problems were more likely to report four or more physician visits during
      the past year, but no statistically significant differences were seen among
      children reported to be in "fair" or "poor" health. Controlling for confounding
      variables, children in the top quartile of the Behavior Problems Index are
      significantly more likely to report four or more visits during the past year and
      two or more visits during the past 2 weeks compared with other children. Anxious
      or depressed and antisocial subscales of the Behavior Problems Index showed
      independent and significant associations with four or more physician visits in
      the past year. CONCLUSION: Children with parent-reported behavior problems are
      likely to have more frequent physician visits compared with children without
      behavior problems, even when confounding sociodemographic and health status
      variables are controlled. The association is concentrated among physically
      healthy children.

PMID- 8556119
TI  - Management of 168 neonates weighing more than 2000 g receiving intrapartum
      chemoprophylaxis for chorioamnionitis. Evaluation of an early discharge strategy.
AB  - OBJECTIVE: To determine whether sequential laboratory and clinical evaluations
      during the first 3 days of postnatal life can be used to safely limit the
      duration of antibiotic therapy for term neonates whose mothers received
      intrapartum antibiotic treatment for intra-amniotic infection (ie,
      chorioamnionitis). METHODS: Since postpartum neonatal body fluid cultures can be
      falsely negative because of transplacental passage of maternal antibiotics, we
      prospectively followed up 6620 pregnancies for 28 months (December 1991 through
      March 1994) for the occurrence and treatment of chorioamnionitis. Neonatal
      antibiotic therapy was initiated and limited to 3 days or continued for 7 days or
      more in neonates with abnormal laboratory values or clinical signs that were
      consistent with sepsis on day 3 of postnatal age. Both groups were observed in
      the hospital for 24 to 48 hours after antibiotics were discontinued. RESULTS: Of
      the 6620 pregnancies, 158 infants (2.4%) born to 155 mothers received intrapartum
      antibiotics for chorioamnionitis; 10 additional neonates diagnosed as having
      chorioamnionitis were transported from other hospitals (N = 168). Because of the
      absence of signs and negative cultures, 82% (137/168) were treated with
      antibiotics for 3 days, while 18% (31/168) received 7 days or more of therapy. In
      84% of the 3-day group, discharge was accomplished by postnatal day 4 or 5,
      whereas all of the 7-day or more group were discharged after day 8. Follow-up
      calls placed 1 month after discharge disclosed no adverse outcomes or hospital
      readmissions in any of the infants in this survey. CONCLUSIONS: Neonates with
      infection who are born to mothers pretreated with antibiotics for intra-amniotic
      infection can be reliably identified less than 72 hours after birth and treated
      appropriately. As 82% of at-risk patients are asymptomatic and have a negative
      body fluid culture, our data support the position that a full course of
      antibiotic therapy can be restricted to only those patients with clinical or
      laboratory signs of sepsis (18%). This will effective reduce the average length
      of hospital stay for intrapartum-treated neonates by a minimum of 3 to 4 days
      compared with a commonly used empiric therapy approach of continuing medication
      for 7 days or more. Perhaps hospital discharge can be further shortened if a 1-
      to 2-day posttreatment observation period is eliminated for all patients except
      those with a positive body fluid culture.

PMID- 8556120
TI  - Prospective study of recurrent radial head subluxation.
AB  - OBJECTIVES: To calculate a recurrence rate for radial head subluxation (RHS) and
      to identify risk factors for recurrence. DESIGN: Prospective cohort study.
      SETTING: Pediatric emergency department of an urban, tertiary care children's
      hospital. PATIENTS: Consecutive sample of 107 children younger than 6 years with
      definite (n = 94) or probable (n = 13) RHS enrolled during a 6-month period and
      followed up for at least 12 months. MAIN OUTCOME MEASURE: Recurrent episodes of
      RHS. RESULTS: Follow-up information was available on 86.9% (93/107) patients,
      with a mean +/- SD of 16.4 +/- 1.9 months (range, 12 to 20 months). Of these 93
      patients, 22 (23.7%) had recurrent RHS. Among the patients who had their first
      episode of RHS during the study period (n = 76), those with recurrences were
      significantly younger than those without (21.7 +/- 9.9 months vs 29.2 +/- 13.5
      months, respectively, P = .04, t test). Those 24 months or younger had a relative
      risk of 2.60 for one or more recurrences during the study period (95% confidence
      interval, 1.04 to 6.30) compared with those older than 24 months. No differences
      were observed in duration of follow-up, sex, elbow involved in the initial
      episode, or family history of RHS between those with and without recurrences.
      CONCLUSIONS: Recurrent RHS occurs in nearly one fourth of patients, and those 24
      months or younger are at greatest risk. Sex, family history, and the elbow
      involved in the initial episode are not risk factors for recurrence.

PMID- 8556121
TI  - Cardinal clinical signs in the differentiation of heart murmurs in children.
AB  - OBJECTIVE: To determine the diagnostic accuracy of clinical assessment of heart
      murmurs in children and specific clinical features that are predictive of cardiac
      disease. DESIGN: Concurrent case series with pretest-posttest assessment.
      SETTING: Pediatric cardiology outpatient clinic. PARTICIPANTS: Five full-time
      academic pediatric cardiologists. MEASURES: For each of 222 consecutive patients
      who were seen for first-time evaluation of a heart murmur, the clinical findings
      and diagnostic impressions were recorded after clinical assessment. The results
      of electrocardiograms and echocardiograms were then reviewed, and changes in
      diagnostic impressions were recorded and compared with the original impressions.
      RESULTS: The prevalence of cardiac disease was 33%. Clinical assessment
      differentiated those patients with pathologic murmurs with a sensitivity of 92%,
      specificity of 94%, positive predictive value of 88%, and negative predictive
      value of 96%. If diagnostic uncertainty was considered an indication for
      echocardiography, then sensitivity and specificity increased to 97% and 98%,
      respectively. Missed disease included only trivial or minor lesions. Clinical
      features that were independently predictive of the presence of disease included
      murmurs that were pansystolic (odds ratio [OR], 54.0), grade 3 or more in
      intensity (OR, 4.84), heard best at the left upper sternal border (OR, 4.24) and
      harsh in quality (OR, 2.37), and the presence of an abnormal second heart sound
      (OR, 4.09) and an early or midsystolic click (OR, 8.35). CONCLUSIONS: Clinical
      assessment by a pediatric cardiologist is sufficient to distinguish pathologic
      from innocent heart murmurs. A genetic approach by using specific clinical
      features that are independently associated with disease may have some practical
      utility to noncardiologists.

PMID- 8556122
TI  - School-based health centers. Students' access, knowledge, and use of services.
AB  - OBJECTIVE: To examine students' knowledge, barriers to access, and use of
      services at two school-based health centers. DESIGN: In-person survey. SETTINGS:
      Two urban public schools in Baltimore, Md. PARTICIPANTS: One hundred forty-nine
      middle school and 131 high school African-American students. The response rate
      was 84%. MAIN OUTCOME MEASURES: Knowledge about center operations and services,
      reported barriers to access to the center, and reported use of the center.
      RESULTS: Knowledge about center operations and services was generally high.
      However, knowledge was low with respect to the need for an appointment for non
      emergency visits (40% correct) and the availability of dental service referrals
      (51% correct). One fifth of students incorrectly reported their enrollment
      status. Boys were more likely to report that they knew about the availability of
      sports physical examinations (odds ratio, 3.7), and girls were more likely to
      report that they knew about reproductive services (odds ratio, 3.0). The most
      frequently identified barriers to access were difficulty in obtaining a teacher's
      permission to leave class (55%), requiring parental permission for enrollment
      (31%), and concern about confidentiality (26%). Barriers to access were reported
      more frequently by students in the middle school than by students in the high
      school. Seven eighths of enrolled students reported that they had used the center
      in the past year, but only a third would use it if they woke up on a Monday with
      a bad cough and needed to see a physician or nurse. CONCLUSIONS: Despite
      increasing the availability of primary care services by locating health centers
      in schools, some barriers to access remain. School-based health centers could
      more actively promote awareness of their operation and services among students
      and their parents.

PMID- 8556123
TI  - Youth with chronic conditions and their transition to adulthood. Findings from a
      Finnish cohort study.
AB  - OBJECTIVE: To explore the effect of chronic health conditions in adolescence on
      eventual transitional paths and young adult functioning in a cohort of Finnish
      youths. DESIGN: Survey in school at age 16 years followed by postal questionnaire
      at age 22 years. METHODS: Youths who had reported persistent chronic conditions
      at ages 16 and 22 years were compared with peers without chronic health
      conditions, using two-way analysis of variance for continuous outcomes and
      logistic regression models for dichotomous outcomes, adjusting for socioeconomic
      differences. MAIN OUTCOME MEASURES: Health status, chronic conditions, personal
      characteristics (including self-esteem), health behavior, education, family
      background, personal relations, and depression. RESULTS: Adolescents with chronic
      health conditions attained levels of psychosocial well-being, education, and
      marriage or dating as young adults similar to their peers without chronic
      conditions. Most of them experienced a successful transition to adulthood.
      Females with chronic conditions were more likely than women without chronic
      conditions to have moved away from their family of origin and to be living with a
      spouse or steady partner. Our findings also suggest that males with chronic
      conditions from white-collar family backgrounds may be at increased risk for
      symptoms of depression in early adulthood. Youths with chronic conditions had
      similar rates of nicotine and alcohol consumption as their healthy peers.
      CONCLUSION: Our findings suggest that in this cohort, most adolescents with
      common chronic conditions had a successful transition to adulthood.

PMID- 8556124
TI  - Weight perception of adolescent dancing school students.
AB  - OBJECTIVE: To study the hypothesis that underweight may be more prevalent among
      dancing school students than among nondancing school girls, and that their
      teachers and peers may play a role in developing this tendency. DESIGN: A case
      control study on a convenience sample. SETTING: Two local dancing schools and one
      neighboring regular school. PARTICIPANTS: Forty ballet students, aged 13 to 17
      years, from four classes and 29 age-matched girls in four regular classes.
      INTERVENTION: None. MEASUREMENTS/MAIN RESULTS: Each pupil was asked to classify
      herself and her peers as underweight, normal, or overweight; teachers were asked
      to classify their pupils by the same categories. Results were compared with an
      objective score, weight as a percentage of ideal weight for height, in which less
      than 85% indicates underweight; 85% to 115%, normal; and more than 115%,
      overweight. A higher prevalence of underweight as well as a significant tendency
      to overestimate self-evaluation was found among dancing students. Dancing
      teachers' evaluation tended to be inaccurate, especially regarding their
      underweight students. CONCLUSIONS: The atmosphere in dancing classes may
      encourage striving for thinness beyond normal limits. Ballet teachers may play a
      significant role in this process. We suggest that physicians and nutritionists be
      involved in ballet schools.

PMID- 8556125
TI  - Physicians' documentation of sexual abuse of children.
AB  - OBJECTIVES: To assess the quality of documentation by physicians in their
      evaluations for sexual abuse of children and to define factors that affect
      documentation. DESIGN: Cross-sectional survey and blinded chart review. SETTING:
      A statewide program for child abuse evaluations. PARTICIPANTS: Physicians (n =
      145) who performed evaluations during fiscal year 1992-1993 were surveyed. Up to
      five randomly chosen medical records (n = 548), obtained from each eligible
      physician, were reviewed. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A survey
      of physicians who participated in the statewide program was made in summer 1993,
      with 78% participation. Knowledge scores were derived from the survey based on a
      comparison with the responses of a panel of five experts. Charts that were
      obtained from eligible physicians were assessed by two blinded reviewers.
      Documentation of the history and physical examination was evaluated as good or
      excellent by 30% and 23% of the physicians, respectively. Factors that were
      positively associated with better documentation of the history included a more
      structured format for the record, continuing medical education courses on sexual
      abuse of children, female gender, and a history of disclosure (P < .005 for all).
      Factors that were related to good documentation of the physical examination
      included structured records, continuing medical education courses, female gender,
      and knowledge scores. Factors that were not related to knowledge or documentation
      included the number of evaluations performed, practice group size or location,
      age of the physician, and a physician's reading of journal articles about sexual
      abuse of children. CONCLUSION: Quality of evaluations for sexual abuse of
      children may be improved by the use of structured records and participation in
      continuing medical education courses with regard to sexual abuse of children.

PMID- 8556126
TI  - Utility of a risk assessment questionnaire in identifying children with lead
      exposure.
AB  - OBJECTIVE: To evaluate the utility of the Centers for Disease Control and
      Prevention (CDC) Risk Questionnaire and a behavioral risk factor questionnaire in
      identifying children with blood lead concentrations of 0.48 mumol/L (10
      micrograms/dL) or more. DESIGN: Cross-sectional study of 463 urban Massachusetts
      children (6 to 72 months of age) screened for lead with venous blood. RESULTS:
      Twenty-two percent of the children had elevated blood lead concentrations. Of the
      five CDC questions, only one was significantly associated with an increased
      adjusted odds ratio for elevated blood lead: having a sibling, housemate, or
      playmate who was followed up or treated for lead poisoning (odds ratio, 2.7; 95%
      confidence interval, 1.7 to 4.2; P < .001). Children who had at least one
      positive or equivocal response to any of the five CDC questions (n = 318 [68.7%])
      were not at higher risk than were children who displayed a negative response to
      all five questions (odds ratio, 1.1; 95% confidence interval, 0.7 to 1.8; P =
      .69). Of nine behaviors surveyed, two were associated with an increased adjusted
      odds for elevated blood lead: use of a pacifier (odds ratio, 2.4; 95% confidence
      interval, 1.3 to 4.4; P = .01) and playing near the outside of the home (odds
      ratio, 3.4; 95% confidence interval, 2.0 to 5.8; P < .001). CONCLUSIONS: In this
      population of children, the CDC risk questionnaire did not identify a group at
      higher risk for lead exposure. We suggest that practitioners in urban communities
      screen all children according to the same schedule. We conclude that risk factors
      differ by community and no risk questionnaire developed at the national level
      should be applied across communities to target screening.

PMID- 8556127
TI  - Psychiatric and developmental disorders in families of children with attention
      deficit hyperactivity disorder.
AB  - OBJECTIVE: To evaluate whether a pediatric family history obtained via a brief
      parent interview would reveal a high prevalence of psychiatric and developmental
      disorders in the family members of children with attention-deficit hyperactivity
      disorder (ADHD) compared with a group of children with another chronic
      developmental disability, Down syndrome (DS). DESIGN: A controlled cross
      sectional group comparison study. SETTING: An interdisciplinary hyperactivity and
      learning problem clinic and a DS clinic located in a large, urban tertiary care
      teaching hospital in Chicago, Ill. PARTICIPANTS: A total of 140 children with
      ADHD and 163 children with DS of comparable socioeconomic status. MEASURES: Using
      a screening questionnaire and parent interview, the development pediatricians
      obtained a family history. RESULTS: By parent report, children with ADHD were
      significantly more likely than the control children with DS to have a parent
      affected by alcoholism (P = .007), other drug abuse (P < .001), depression (P <
      .001), delinquency (P < .001), learning disabilities (P < .001), and ADHD (P <
      .001). Similar patterns were evidenced in other first- and second-degree
      relatives. CONCLUSIONS: The high reported frequency of psychiatric and
      developmental disorders in the families of children with ADHD requires that the
      treating clinician explore the area of family psychiatric and developmental
      history and use the findings to formulate a comprehensive treatment plan that
      includes anticipatory guidance and psychosocial intervention.

PMID- 8556128
TI  - Sports medicine training during pediatric residency.
AB  - OBJECTIVES: To assess how sports medicine is taught within pediatric residency
      programs and to determine the level of comfort that pediatric graduates have in
      managing common sports injuries. INTERVENTION: Investigator-prepared cross
      sectional survey. METHOD: A survey questionnaire was mailed to 203 pediatric
      chief residents of pediatric residency programs in the United States.
      MEASUREMENTS/MAIN RESULTS: Seventy-three percent of the questionnaires were
      returned. Most pediatric chief residents (73%) reported that their program
      provided lectures on pediatric sports medicine topics. Lecture time devoted to
      sports medicine topics was reported to be less than 6 hours for many residency
      programs (83%). Instruction on the medical criteria for exclusion from sports was
      provided to 64% of the chief residents. Of those residents who completed the
      survey, 55% reported that clinical sports medicine training was available in
      their programs. Rotations in adolescent medicine (28%), pediatric orthopedics
      (26%), and ambulatory pediatrics (9%) provided the bulk of clinical training.
      Clinical exposure to sports medicine was reported to be less than 5 hours in a
      large number of programs (43%). Most of the chief residents reported that they
      would refer six of eight pediatric sports injuries for diagnosis and management.
      CONCLUSIONS: The pediatric chief residents who completed the survey received
      limited didactic instruction or clinical training in sports medicine. Because
      pediatricians are primary care physicians for many children and adolescents who
      participate in sports, pediatric residency directors should consider integrating
      sports medicine instruction into their programs.

PMID- 8556129
TI  - Radiological case of the month. Neonatal osteomyelitis diagnosed by ultrasound.

PMID- 8556130
TI  - Picture of the month. Glycogen storage disease type la (von Gierke disease)
      complicated by gouty arthritis and xanthomatosis.

PMID- 8556131
TI  - Pathological case of the month. Spondylothoracic dysplasia with multiple
      congenital cardiac anomalies.

PMID- 8556132
TI  - Routine chest measurement in the newborn.

PMID- 8556133
TI  - Pyloric stenosis in premature infants.

PMID- 8556134
TI  - Pediatrician and compounding pharmacist: a dangerous liaison.

PMID- 8556135
TI  - Abusive spiral fractures of the humerus: a videotaped exception.

PMID- 8556136
TI  - Long-term outcome after severe brain injury in preschoolers is worse than
      expected.

PMID- 8556137
TI  - Infantile colic: seasonal incidence and crying profiles.

PMID- 8556138
TI  - Oxyradical generation after resuscitation of hemorrhagic shock with blood or
      stroma-free hemoglobin solution.
AB  - Hypovolemic states are characterized by inadequate tissue perfusion; when this
      state is reversed, the reintroduction of oxygen is accompanied by the excess
      generation of oxyradicals and these, in turn, may cause "reperfusion injury" in
      susceptible tissues. When hemoglobin solution is used to resuscitate the
      hypovolemic state, the generation of oxyradicals may be enhanced by catalytic
      means. The generation of oxyradicals was estimated in dogs subjected to the acute
      removal of 35 ml/Kg blood, and resuscitated 45 mins thereafter with an equal
      volume of either autologous blood (Group I, n = 6) or 6% stromafree hemoglobin
      solution (S.F.H.S.) (Group II, n = 6). Hepatic and pancreatic enzymes were
      measured in blood drawn at intervals. The hypovolemic state was characterized by
      profound hypotension which was reversed by resuscitation. Oxyradical generation
      in arterial blood samples, drawn at various times, was estimated by the
      generation of oxidation products (2,3- and 2,5-dihydroxybenzoic acid) of
      exogenously administered sodium salicylate, determined by HPLC in plasma samples
      extracted with diethyl ether. Salicylate oxidation products rose significantly
      above the baseline value in Group I dogs, whereas they rose 5-6-fold higher than
      the baseline values in those of Group II. The actual values attained and the
      increments were significantly (p < .05) greater in Group II than in Group I. In
      the group resuscitated with S.F.H.S., catalytically active iron concentration in
      plasma also rose 10-12-fold higher and was associated with spuriously elevated
      levels of gamma-glutamyl transferase due to interference with the assay. These
      findings are consistent with the hypothesis that blood-resuscitation of
      hypovolemic shock is accompanied by oxyradical generation of a modest degree; in
      contrast, S.F.H.S.-resuscitation introduces catalytically active iron and is
      accompanied by oxyradical generation of a significantly greater degree.

PMID- 8556139
TI  - Diaspirin crosslinked hemoglobin (DCLHb) attenuates bacterial translocation in
      rats.
AB  - Intestinal barrier function is compromised following severe hemorrhage which may
      allow bacterial translocation (BT) to occur and subsequently initiate a systemic
      response leading to multiple system organ failure (MSOF). This study compared BT
      following hemorrhage and resuscitation with lactated Ringer's solution (LR) or
      diaspirin crosslinked hemoglobin solution (DCLHb). Rats (250-350 grams) were
      hemorrhaged to a base deficit of 15 +/- 2 mmol/L and immediately resuscitated
      with either 3:1 LR or 1:1 DCLHb based on shed blood volume. Four hours following
      resuscitation, the mesenteric lymph node complex was harvested, homogenized and
      plated onto MacConkey and Columbia CNA agar culture media. Facultative anaerobic
      and obligate aerobic bacteria were identified 48 hours later in 11/22 (50%) LR
      treated rats and in 4/21 (19%) DCLHb-treated rats (p < or = 0.05). Following
      resuscitation, base excess (BE) and central venous oxygen saturation (SvO2) were
      not only restored to baseline but were significantly greater (p < or = 0.05) in
      DCLHb-treated rats than in LR-treated rats. In a separate group of rats subjected
      to the same hemorrhage and resuscitation protocol, mean arterial pressure in
      DCLHb-treated rats, but not LR-treated rats, was restored to baseline by 15
      minutes and remained at or above baseline for up to 4 hrs. Twenty-four hour
      survival was 50% in LR-treated rats and 77% in DCLHb-treated rats (p > 0.05).
      These data suggest that DCLHb is superior to LR in restoring tissue oxygen
      delivery, as judged by BE and SvO2. Furthermore, since DCLHb restores oxygen
      delivery and attenuates BT, early resuscitation with DCLHb may limit gut ischemia
      and subsequent gut barrier failure and hence prevent the development of sepsis,
      MSOF and subsequent death.

PMID- 8556140
TI  - Influence of steric stabilization of liposome-encapsulated hemoglobin on Listeria
      monocytogenes host defense.
AB  - Liposome-encapsulated hemoglobin (LEH) products are being investigated as
      potential blood substitutes. To determine if changes in LEH composition can
      modify the immune response, red blood cell substitutes based on conventional
      lipids containing phosphatidylinositol (LEH1) and sterically stabilized lipid
      vesicles containing polyethylene glycol phosphatidylethanolamine (LEH2) were
      tested for effects on host resistance. On Day 0, groups of 18 to 20 female CD-1
      mice were given an intravenous (i.v.) infectious challenge with a 20% lethal dose
      of Listeria monocytogenes. Mice received a single i.v. dose of LEH1, LEH2, or
      albumin vehicle on Day +1 or Day -3 relative to infectious challenge. Mice dosed
      with LEH1 and LEH2 on Day +1 died rapidly from Listeria infection; but mice dosed
      with LEH2 lived significantly longer than did mice receiving LEH1. By contrast,
      when administered on Day -3, LEH1 had no significant effect on host immunity,
      while LEH2 increased susceptibility to Listeria infection. In addition, LEH1 and
      LEH2 both caused significant reduction of phagocytic activity as measured by rat
      alveolar macrophage (AM) ingestion of latex microspheres. AM incubated 4 hr with
      either LEH1 or LEH2 prior to addition of microspheres ingested fewer beads in a
      dose-dependent manner. No difference in in vitro phagocytic activity was observed
      between LEH1 or LEH2. The inability to differentiate LEH formulations based on in
      vitro phagocytic activity suggests that the in vivo Listeria infection model may
      be more relevant in discerning the immunotoxicity of the LEH formulations tested.

PMID- 8556141
TI  - Enzyme replacement therapy in ENU2 phenylketonuric mice using oral
      microencapsulated phenylalanine ammonia-lyase: a preliminary report.
AB  - The presence of an extensive enterorecirculation of amino acids between the
      intestine and the body allows the removal of systemic phenylalanine in PKU rats
      by oral microencapsulated phenylalanine ammonia lyase. The work presented in this
      article has the main goal of assessing the feasibility of yeast phenylalanine
      ammonia-lyase (PAL) loaded collodion microcapsules in reducing elevated plasma
      phenylalanine concentrations to standard levels in genetically mutated PKU mice,
      within a 30 day time frame. The distinguishing aspect from previous studies lies
      in the available animal model. Rather than artificial induction of elevated
      phenylalanine plasma levels, the mice representing the human phenylketonuric
      condition, are mutated strains which are deficient in the enzyme phenylalanine
      hydroxylase. The first in vivo study established a method for orally feeding
      microcapsules, both control and enzyme loaded, over 30 consecutive days, by
      mixing with soft, unripened cheese. Under this unique regime a decrease of 51.3%
      +/- 9.02% in phenylalanine plasma levels was observed after 23 days. Reduction in
      the phenylalanine plasma levels to within the desired maintenance range of 250
      1000 umol/L was observed in 2 out of 4 PAL treated mice, with only 50% of the PAL
      dose used in previous rat studies by Chang's group. The second animal study
      confirmed the finding in the first in vivo study that there is no significant
      decrease in the plasma phenylalanine levels within the first seven days. This may
      be due to the severely deteriorated physical condition of the ENU mice used, the
      PAL enzyme preparations available or the fact that normal mice contain 10 times
      the amount of phenylalanine hydroxylase as compared with humans, thus requiring
      larger doses of PAL in order to be effective in a shorter time span.

PMID- 8556142
TI  - Superoxide dismutase and catalase cross-linked to polyhemoglobin reduces
      methemoglobin formation in vitro.
AB  - Superoxide dismutase (SOD) and catalase (CAT) were evaluated for their ability to
      reduce methemoglobin formation in chemically cross-linked hemoglobin that was
      incubated in Tris-HCl buffer. Two parallel studies were carried out using
      identical experimental conditions with one exception only. This involved the
      physical state of SOD and CAT in solution such that the enzymes were either cross
      linked directly to hemoglobin (hemoglobin-SOD-CAT) or simply incubated with
      polyhemoglobin. The concentration of SOD and CAT was subsequently varied to
      examine and compare the effect on the rate of methemoglobin formation between the
      two experiments. Overall, a comparison between the results clearly indicated that
      cross-linking SOD and CAT to hemoglobin was more effective at reducing
      methemoglobin levels than incubating polyhemoglobin with SOD and CAT. More
      specifically, the incubation experiment would require an enzyme concentration
      exceeding twice that cross-linked to hemoglobin in order to achieve a similar
      beneficial effect. However, it was more striking to observe that the presence of
      SOD and CAT during the cross-linking reaction had markedly reduced the initial
      formation of methemoglobin. When SOD and CAT were included during the chemical
      process of generating polyhemoglobin, about 7% methemoglobin was formed in the
      cross-linked hemoglobin-SOD-CAT product. By comparison, methemoglobin had
      increased about 20% after the cross-linking reaction when generating
      polyhemoglobin.

PMID- 8556143
TI  - 11th Montreux Symposium on Liquid Chromatography--Mass Spectrometry,
      Supercritical Fluid Chromatography--Mass Spectrometry, Capillary Electrophoresis-
      Mass Spectrometry and Tandem Mass Spectrometry. Montreux, Switerland, 9-11
      November 1994.

PMID- 8556144
TI  - Determination of organophosphorus pesticides and their transformation products in
      river waters by automated on-line solid-phase extraction followed by thermospray
      liquid chromatography-mass spectrometry.
AB  - The trace-level determination of ten priority organophosphorus (OP) pesticides
      (e.g., chlorpyrifos-methyl, diazinon, disulfoton, fenthion, fenamiphos) and
      various transformation products (TPs; e.g., disulfoton sulfoxide, fenthion
      sulfoxide etc.) using automated on-line solid-phase extraction (SPE) with C18
      precolumns followed by LC-MS and thermospray interface with time-scheduled
      selected-ion monitoring (SIM) was developed. Two main ions (usually [M+H]+ and
      [M+NH4]+ or [M+CH3CN]+) were used for each pesticide in the positive ion (PI)
      detection mode, while [M-H]- and [M+HCOO]- ions were used in the negative ion
      (NI) mode. The proposed method requires 100 ml of sample for a limit of detection
      (LOD) of 0.01-0.1 microgram/l. Calibration graphs were constructed by
      preconcentrating 100 ml of water spiked with the pesticide mixture at various
      concentrations (from 0.025 to 2 microgram/l). Good linearity was observed for
      most of the analytes studied. The experimental setup described in this paper was
      applied to study the kinetics of degradation of ten organophosphorus pesticides
      in spiked river water samples. The different samples were first analyzed by an
      automated on-line precolumn exchange system (OSP-2) followed by LC with diode
      array detection. To confirm the identity of the organophosphorus pesticides
      detected, the samples were then analyzed by automated on-line SPE-LC-MS. The
      method permitted unequivocal identification of many of the TPs formed during the
      experiments, e.g., the oxo-derivatives of chlorpyrifos-methyl, temephos and
      pyridafenthion, fenamiphos sulfoxide. Many of these TPs are here reported for the
      first time since previously used MS-based techniques were not sensitive enough.

PMID- 8556145
TI  - Trace determination of herbicides in estuarine waters by liquid chromatography
      high-flow pneumatically assisted electrospray mass spectrometry.
AB  - High-flow pneumatically assisted electrospray (ESP) was applied to the
      characterization of triazine (atrazine, simazine, ametryne, cyanazine,
      deethylatrazine and deisopropylatrazine), phenylurea (chlortoluron++,
      isoproturon, diuron, linuron and diflubenzuron) and other priority herbicides
      (alachlor, metolachlor). In LC-ESP-MS the [M+Na]+ ion was used as the base peak
      in most cases, with the exception of chlorotriazines, which showed [M+H]+ as the
      base peak. When LC-TSP-MS was used, [M+H]+ was the base peak for many of the
      pesticides, with the exception of linuron and diflubenzuron, which showed
      [M+NH4]+ as the base peak. The ESP results were compared with those obtained with
      thermospray (TSP). LC-TSP-MS offered greater sensitivity for triazines than
      phenylurea herbicides, whereas the use of LC-ESP-MS offered an enhancement in
      sensitivity for phenylurea herbicides. As regards the fragmentation obtained
      using both techniques, ESP offered a considerable amount of structural
      information for the different chlorotriazines studied when the extraction voltage
      was increased from 20 to 40 V. Liquid-liquid extraction with dichloromethane was
      used for the trace enrichment of the different herbicides in estaurine water
      samples from the Elorn river (France). The presence of the different triazine
      metabolites, atrazine, simazine, metolachlor, isoproturon and diuron was
      confirmed by both LC-MS techniques.

PMID- 8556146
TI  - Polar organic pollutants in the Elbe river. Liquid chromatographic-mass
      spectrometric and flow-injection analysis-mass spectrometric analyses
      demonstrating changes in quality and concentration during the unification process
      in Germany.
AB  - During the unification process of the two German states from 1989 to 1994, water
      extracts from the Elbe river were analyzed by gas chromatography-mass
      spectrometry (GC-MS) and by high-performance liquid chromatography (HPLC)
      combined with ultraviolet (UV) and/or mass spectrometric detection (MS) in order
      to monitor the pollutants in one of the most contaminated European rivers. After
      column chromatography (LC) or flow-injection analysis (FIA) bypassing the
      analytical column, ionization was performed by a thermospray interface (TSP).
      Semiquantitative estimations of the pollution of the Elbe were made from the
      total-ion current traces (TIC) of the extracts. Determination of the total
      dissolved organic carbon (DOC) indicated a reduction of more than 55% of
      pollutants in the water phase. The pollutants were identified by tandem mass
      spectrometry (MS-MS), generating daughter-ion spectra by collision-induced
      dissociation (CID) using either column chromatography or direct mixture analysis.
      Compound-specific analyses indicated a reduction in the amount of pollutants as
      well as a change in their composition. This could be explained by reduced
      industrial production and by intensified construction of biological sewage
      treatment plants.

PMID- 8556147
TI  - Separation and detection of 4-hexadecylaniline maltooligosaccharide derivatives
      with packed capillary liquid chromatography-frit fast atom bombardment-mass
      spectrometry.
AB  - A LC-MS method is under development for the separation and detection of mixtures
      of native glycolipids and of oligosaccharide derivatives. The LC system is based
      on slurry-packed capillary columns. Frit fast atom bombardment (frit-FAB) is used
      as the LC-MS interface and ionisation technique and the column is connected to
      the frit via a 50 microns I.D. fused-silica capillary liner. Post column addition
      of matrix is achieved using a 50 microns I.D. fused-silica capillary liner with
      2.5% (v/v) matrix solution. The two liners are joined through a septum and end
      side by side against the frit. The detection limit was found to be less than 1
      pmole in the negative ion mode. A mixture of tetra to deca maltooligosaccharides
      reductively aminated with 4-hexadecylaniline (M4-10-HDA) was separated on a
      straight phase silica column using gradient elution.

PMID- 8556148
TI  - Liquid chromatography combined with thermospray and continuous-flow fast atom
      bombardment mass spectrometry of glycosides in crude plant extracts.
AB  - In crude plant extracts, constituents of biological or pharmaceutical interest
      often exist in the form of glycosides. Off-line mass spectral investigations of
      these metabolites require soft ionisation techniques such as desorption chemical
      ionisation (DCI) or fast atom bombardment (FAB) if information on molecular mass
      or sugar sequence is desired. In LC-MS, glycosides can be ionised by using
      thermospray (TSP), continuous-flow fast atom bombardment (CF-FAB) or other
      interfaces. These techniques are thus potentially applicable to the on-line
      analysis of glycosides and can be applied to plant extract analysis. Thermospray
      (TSP) used with ammonium acetate as buffer provides mass spectra similar to those
      obtained with DCI-MS using NH3 and is potentially applicable to the on-line
      analysis of relatively small glycosides bearing no more than three sugar units.
      CF-FAB provides cleaner MS spectra than static FAB due to the lower concentration
      of the matrix used and can be applied to more polar compounds such as glycosides
      with a larger number of sugars. The use of a special setup involving post-column
      addition of the buffer or the matrix and splitting allows LC-UV, TSP LC-MS and CF
      FAB LC-MS to be performed with the same standard HPLC conditions. Different crude
      plant extracts containing various types of glycosides with one to eight sugar
      units have been analysed by both TSP and CF-FAB. Cardenolides from Nerium odorum
      (Apocynaceae) and saponins from Swarzia madagascariensis (Leguminosae), Aster
      scaber and Aster tataricus (Asteraceae) have been studied by LC-MS. The
      combination of these two interfaces for the HPLC screening of crude plant
      extracts is discussed.

PMID- 8556149
TI  - Liquid chromatographic-mass spectrometric studies on the enzymatic degradation of
      beta-endorphin by endothelial cells.
AB  - An on-line HPLC-mass spectrometric procedure with an electrospray atmospheric
      pressure ionization (ESI-API) ion source was developed to identify the enzymatic
      degradation products (peptides) generated by incubation of human beta-endorphin
      (h beta E) with cultured aortic endothelial cells. The samples from the complex
      incubation mixture were prepurified and enriched using a small reversed-phase
      (RP) perfusion precolumn. Flow switching was applied to transfer the peptides
      from this precolumn to the analytical RP column of 2 or 0.32 mm I.D. and to
      separate them by gradient elution. The peptides were detected by means of an on
      line coupled triple quadrupole mass spectrometer (TSQ 700) with an ESI-API ion
      source operated in the positive ion mode. This MS system behaves as a
      concentration sensitive detector at flow-rates from 5 to 150 microliters/min. MS
      MS experiments supported the unambiguous assignment of the peptide structures.
      Thus most of the peptide fractions were identified and the region 16-17-18 (-L-F
      K-) of h beta E was found to be primarily attacked by the enzymes of the
      endothelial cells.

PMID- 8556150
TI  - Enhanced sensitivity for peptide mapping with electrospray liquid chromatography
      mass spectrometry in the presence of signal suppression due to trifluoroacetic
      acid-containing mobile phases.
AB  - A method is described for improving the sensitivity of peptide mapping with
      electrospray liquid chromatography--mass spectrometry using trifluoroacetic acid
      (TFA) containing HPLC mobile phases. The signal suppressing effects of TFA are
      shown to be due to the combined effect of ion-pairing and surface tension
      modifications. The post-column addition of a propionic acid-2-propanol (75:25,
      v/v) in a 1:2 proportion with the HPLC mobile phase counteracts the deleterious
      effects of TFA resulting in 10-100 x improvement of the signal-to-noise ratio.
      The system described introduces total HPLC flow (plus additive) directly into the
      electrospray source without splitting. Using 2.1 mm I.D. HPLC columns, minimum
      detectable quantities are below 40 pmol total protein. As examples, separations
      of proteolytic enzyme digests of several proteins are shown using standard HPLC
      conditions, comparing results with and without the addition of propionic acid.
      The application of the technique is shown in more depth in the identification of
      oxidative modification sites in glutamine synthetase. In this application, the
      enhanced sensitivity allowed location of a modified residue by comparison
      endoproteinase Lys C digest of native and oxidized forms of the protein without
      extensive sample preparation or concentration. A third application demonstrates
      the identification of glycosylation sites in an endoproteinase Arg C digest of
      single-chain plasminogen activator through the use of in-source collisionally
      induced dissociation.

PMID- 8556151
TI  - On-line coupling of micellar electrokinetic chromatography to electrospray mass
      spectrometry.
AB  - The possibility of selectivity enhancement in capillary electrophoresis-mass
      spectrometry (CE-MS) by hyphenating micellar electrokinetic chromatography (MEKC)
      and electrospray mass spectrometry (MS) is described for two quaternary ammonium
      compounds. Direct coupling of MEKC to MS is hazardous because of the
      contamination of the ion source due to presence of an excess of micelle forming
      agent in the MEKC buffer. Therefore, a coupled-capillary setup with the
      possibilities of voltage switching and buffer renewal has been designed. Such a
      system allows on-line heartcutting of the zones of interest in the MEKC capillary
      with subsequent transfer via a second capillary to the mass spectrometer.

PMID- 8556152
TI  - Mass spectral analyses of microcystins from toxic cyanobacteria using on-line
      chromatographic and electrophoretic separations.
AB  - The application of capillary electrophoresis and of reversed-phase liquid
      chromatography coupled to electrospray mass spectrometry is presented for the
      analysis of microcystins isolated from toxic strains of Microcystis aeruginosa.
      The separation performance of these two techniques is compared in terms of both
      sensitivity and of resolution of closely related microcystins. Quantitation of
      microcystin-LR present at low micrograms/ml concentrations in cell extracts is
      demonstrated using both techniques. A marked advantage of capillary
      electrophoresis over liquid chromatography was its ability to resolve different
      desmethyl microcystin-LR analogues. Identification of these positional isomers
      was facilitated using capillary electrophoresis combined with tandem mass
      spectrometry (MS-MS). Rationalization of fragment ions observed in MS-MS spectra
      of microcystins was made possible through comparison with 15N labelled
      microcystins obtained from stable isotope feeding experiments. The potential of
      tandem mass spectrometry in providing selective detection of microcystins in cell
      extracts, and in structural characterization of novel microcystins, was also
      investigated.

PMID- 8556153
TI  - Application of a new atmospheric pressure ionization source for double focusing
      sector instruments.
AB  - In three application examples we demonstrate how the capabilities of a modern
      atmospheric pressure ionization (API) source, as a universal LC-MS coupling tool,
      are supplemented by the high mass resolution available on double focusing sector
      instruments. The examples include charge state determination in complex
      electrospray ionization-collisional induced dissociation (ESI-CID) spectra of
      multiply charged ions, mixture analysis of multicomponent samples without prior
      chromatographic separation, and very sensitive and highly specific detection of
      pesticides using atmospheric pressure chemical ionization (APCI).

PMID- 8556154
TI  - Enantiospecific determination of nimodipine in human plasma by liquid
      chromatography-tandem mass spectrometry.
AB  - A direct enantiospecific HPLC assay using tandem mass spectrometric (MS-MS)
      detection via pneumatically-assisted electrospray has been developed for the
      determination of the calcium antagonist nimodipine in human plasma. By the
      addition of ammonium acetate (2 mM) to the purely organic eluent ethanol-n
      heptane (20:80, v/v) charged species (M+NH4+) were producible by electrospray
      ionization at sufficient sensitivity. Routine determination of nimodipine
      enantiomers in human plasma in the working range of 0.5-75 microgram/l plasma for
      each isomer with an accuracy < or = +/- 10% and a precision of about 10% (20%
      close to the limit of quantification) was possible. This was comparable to the
      available LC-GC-MS assay, however, the time required for routine analysis of ca.
      150 unknowns could be reduced from 4 weeks to 1 week.

PMID- 8556155
TI  - Estimation of ranolazine and eleven phase I metabolites in human plasma by liquid
      chromatography-atmospheric pressure chemical ionisation mass spectrometry with
      selected-ion monitoring.
AB  - The estimation of ranolazine, a novel piperazine derivative, and eleven of its
      Phase I metabolites has been undertaken by liquid chromatography-atmospheric
      pressure chemical ionisation mass spectrometry (LC-APCI-MS). Plasma samples,
      taken on day 5 of a multiple-dose study, were extracted by solid-phase extraction
      (SPE) and analysed, using a gradient HPLC system coupled to the APCI source of a
      Finnigan MAT TSQ 700 mass spectrometer. Metabolites were analysed in selected-ion
      monitoring (SIM) mode, using an instrument control language (ICL) procedure. The
      LC-MS combination allowed resolution of all eleven metabolites, including four
      hydroxylated metabolites and five unresolved components. The results from the
      linear regression showed good correlation (r2 > 0.980) for all the metabolites.
      Plasma concentrations indicated that three metabolites were present at levels
      higher than 10% of the parent compound.

PMID- 8556156
TI  - Metabolic studies of an orally active platinum anticancer drug by liquid
      chromatography-electrospray ionization mass spectrometry.
AB  - Bis(acetato)amminedichloro(cyclohexylamine) platinum(IV) (JM216) is a new orally
      administered platinum complex with antitumor properties, and is currently
      undergoing phase II clinical trials. When JM216 was incubated with human plasma
      ultrafiltrate, 93% of the platinum species were protein-bound and 7% were
      unbound. The unbound platinum complexes in the ultrafiltrates of human plasma
      were analysed using a liquid chromatography-electrospray ionization-mass
      spectrometry (LC-ESI-MS) method. Apart from the parent drug, four metabolites
      were identified and characterised. These include JM118
      [amminedichloro(cyclohexylamine) platinum(II)], JM383
      [bis(acetato)ammine(cyclohexylamine)dihydroxo platinum(IV)] and the two isomers
      JM559 and JM518 [bis(acetato)amminechloro(cyclohexylamine) hydroxo platinum(IV)].
      Their elemental compositions were determined by accurate mass measurement during
      the LC analysis, to confirm their identities. Quantitation of these metabolites
      by off-line LC atomic absorption spectroscopy demonstrated that JM118 is the
      major metabolite in plasma from patients receiving JM216 treatment.

PMID- 8556157
TI  - Rapid analysis of beta-agonists in urine by thermospray tandem mass spectrometry.
AB  - A method is described for the analysis of beta-agonists in urine of cattle. The
      method uses solid-phase extraction (SPE), followed by analysis of the resulting
      extract by flow injection thermospray tandem mass spectrometry (TSP-MS-MS).
      Sample preparation is performed using a mixed-bed SPE procedure using a sorbent
      having both hydrophobic and ionic properties. MS-MS analysis following
      thermospray ionization, is performed in single-reaction monitoring parent mode.
      In that way isotope dilution can be used for quantitation of clenbuterol. Data
      are presented on precision and accuracy for clenbuterol and related compounds.
      Furthermore, data acquisition was performed in full-scan neutral loss mode to
      indicate the suitability of flow injection analysis (FIA)-TSP-MS-MS for
      exploratory analysis. Detection of beta-agonists in this mode is based on the
      presence of the N-tert.-butyl-beta-ethanolamino moiety and, in that respect,
      detection of known as well as unknown compounds having this moiety will take
      place. This feature is exemplified by the analysis of samples containing several
      compounds.

PMID- 8556158
TI  - Determination of an endothelin receptor antagonist in human plasma by narrow-bore
      liquid chromatography and ionspray tandem mass spectrometry.
AB  - A method is described for the determination of a new endothelin receptor
      antagonist, Bosentan Ro 47-0203, in human plasma using narrow-bore liquid
      chromatography and ionspray tandem mass spectrometry. After protein precipitation
      with acetonitrile, the compounds were extracted with dichloromethane at pH 11.
      The compounds were chromatographed on a 2 mm I.D. reversed-phase column and
      introduced into the mass spectrometer with an ionspray (pneumatically assisted
      electrospray) interface at a flow-rate of 170 microliters/min without postcolumn
      splitting. Two different internal standards were used for the assay: either a
      structural analogue or a deuterated analogue. The limit of quantification was 0.5
      ng/ml using a 0.5-ml aliquot of plasma. Concentrations of the drug were
      determined in the range 0.5-200 ng/ml. The recovery from human plasma was 87%.
      The new API IIIplus collision cell was about five times more sensitive than the
      original API III cell. The assay was demonstrated to be sensitive, selective and
      robust for the analysis of over 1500 samples.

PMID- 8556159
TI  - Determination of the pesticide diflubenzuron in mushrooms by high-performance
      liquid chromatography-atmospheric pressure chemical ionisation mass spectrometry.
AB  - A method using high-performance liquid chromatography-atmospheric pressure
      chemical ionisation mass spectrometry (HPLC-APCI-MS) has been developed and
      validated for the determination of the insecticide diflubenzuron [1-(4
      chlorophenyl)-3-(2,6-difluorobenzoyl)urea] in mushrooms. Samples were homogenised
      with acetone, extracted into dichloromethane-cyclohexane and further cleaned-up
      by size-exclusion chromatography (SEC). HPLC was performed on an ODS column with
      methanol-water at 1 ml/min. The limit of detection was 0.02 ng/microl (equivalent
      to 0.017 mg/kg in the crop). The calibration was linear over the range 0.025-1.0
      ng/microl. Recovery of diflubenzuron from spiked mushrooms (0.06-0.58 mg/kg) was
      85.5% with a relative standard deviation of 14.5% (n = 56).

PMID- 8556160
TI  - Gas chromatography of 4,4'-diphenylmethane diisocyanate in the workplace
      atmosphere.
AB  - A sensitive gas chromatographic procedure for the determination of 4,4'
      diphenylmethane diisocyanate concentration in air is described. Traps containing
      20-40-mesh silica gel coated with phosphoric acid are used. After the aspiration
      of the air, the silica gel is eluted with sodium hydroxide in methanol. The amine
      formed is then separated with a gas chromatograph and measured with a nitrogen
      phosphorus detector. This can be performed in 7 min. Virtually no breakthrough
      occurs if an air concentration of up to 128 nmol in 20 l is sampled. The
      detection limit based on a 20-1 air sample is 0.7 microgram/m3. Complete analysis
      requires about 30 min. The method was used to determine the concentration of 4,4'
      diphenylmethane diisocyanate in working environments during spraying operations.

PMID- 8556161
TI  - Analysis of the glycoforms of human recombinant factor VIIa by capillary
      electrophoresis and high-performance liquid chromatography.
AB  - The carbohydrate-dependent microheterogeneity of recombinant coagulation factor
      VIIa (rFVIIa) has been characterized by capillary electrophoresis (CE) of the
      native protein and by high-performance liquid chromatography (HPLC) of tryptic
      peptides and of oligosaccharides released by hydrazinolysis. The development of
      the CE analysis is reported here. We have found that application of 1,4
      diaminobutane (putrescine) as additive to the CE separation buffer is essential
      for the separation of the various glycoforms. Under optimum conditions rFVIIa
      migrates as a cluster of six peaks or more. By CE of neuraminidase-treated rFVIIa
      a faster-moving double peak is observed. This indicates that the separation
      obtained is primarily based upon the different content of N-acetyl-neuraminic
      acid of the oligosaccharide structures in rFVIIa. By reversed-phase HPLC of
      tryptic digested neuraminidase treated rFVIIa the glycopeptides containing the
      heavy chain N-glycosylated site elute as two peaks compared to the four peaks
      corresponding to glycopeptides with 0 to 3 N-acetyl-neuraminic acids seen for
      untreated rFVIIa. In high-pH anion-exchange HPLC of the oligosaccharides released
      from native rFVIIa by hydrazinolysis the major peaks elute as oligosaccharides
      with 1 or 2 N-acetyl-neuraminic acids. Oligosaccharides released from
      neuraminidase treated rFVIIa elute earlier compared to oligosaccharides from
      native rFVIIa, but separated into several peaks, indicating heterogeneity for the
      oligosaccharide structures without N-acetyl-neuraminic acid.

PMID- 8556162
TI  - Separation of tryptophan and related indoles by micellar electrokinetic
      chromatography with KrF laser-induced fluorescence detection.
AB  - Micellar electrokinetic chromatography (MEKC) was applied for the separation of
      tryptophan and related indoles. Using a 5 mM sodium borate buffer (pH 9.2)
      containing 50 mM sodium dodecyl sulfate and 5% acetonitrile, eleven indoles were
      baseline separated in under 17 min. Most of the indoles were detected at the nM
      level by native fluorescence using KrF laser-induced fluorescence (LIF), which
      was approximately 100 times more sensitive than UV absorption detection at 200
      nm. Preliminary results show that the MEKC-LIF with direct sample injection is a
      feasible method for assessing indole profiles in diluted urine and serum.

PMID- 8556163
TI  - Use of capillary zone electrophoresis in an investigation of peptide uptake by
      dairy starter bacteria.
AB  - A capillary zone electrophoresis (CZE) method to separate the peptide series val
      glyn, where n is 1 to 4, has been evaluated and compared to separation by
      reversed-phase high-performance liquid chromatography (RP-HPLC). The method was
      able to quantitate peptides present a very low concentrations (down to 0.05 mM)
      with high reproducibility and accuracy and was capable of separating peptides
      differing in size by only a single glycine residue. It could also separate the
      peptides val-gly and leu-gly which differed in only a single side-chain methylene
      group. The method was fast, required small sample volumes, and proved to be
      superior to RP-HPLC. The suitability of the CZE method to analyze peptide uptake
      by dairy starter bacteria is discussed.

PMID- 8556164
TI  - Determination of morphine and related alkaloids in crude morphine, poppy straw
      and opium preparations by micellar electrokinetic capillary chromatography.
AB  - A rapid method for the determination of morphine and related alkaloids in crude
      morphine, poppy straw and opium preparations by micellar electrokinetic capillary
      chromatography (MEKC) has been developed. Morphine, codeine, thebaine, oripavine,
      papaverine, narcotine, narceine, cryptopine and salutaridine were separated in
      less than 10 min using a 70 cm x 50 microm I.D. uncoated fused-silica capillary
      column with a buffer consisting of 10% dimethylformamide, 90% 0.05 M
      cetyltrimethylammonium bromide, 0.01 M potassium dihydrogen orthophosphate, 0.01
      M sodium tetraborate, pH 8.6. An applied voltage of -25 kV and a temperature of
      28 degrees C gave the best separation of the alkaloids. Pholcodine was used as
      the internal standard. The compounds were detected by UV at 254 nm. The levels of
      morphine and related alkaloids determined by MEKC were in good agreement with
      those determined by high-performance liquid-chromatography (HPLC). The
      coefficients of variation for area calculation (%C.V.) for multiple sample and
      standard injections by MEKC were slightly greater than for HPLC but were still
      acceptable (morphine content of poppy straw: %C.V. MEKC 1.7%, %C.V. HPLC 0.3%).

PMID- 8556165
TI  - Biomimetic dye affinity chromatography for the purification of bovine heart
      lactate dehydrogenase.
AB  - Three biomimetic dye ligands bearing as a triazine-linked terminal moiety a
      carboxylated structure, which mimics substrates and inhibitors of L-lactate
      dehydrogenase (LDH), were immobilized on cross-linked agarose Ultrogel A6R. These
      biomimetic dyes are purpose-designed analogues of commercial monochlorotriazine
      Cibacron Blue 3GA (CB3GA) and parent dichlorotriazine Vilmafix Blue A-R (VBAR).
      The corresponding biomimetic adsorbents, along with non-biomimetic adsorbents
      bearing CB3GA and VBAR, were evaluated for their ability to purify LDH from
      bovine heart crude extract. When compared with non-biomimetic adsorbents, all
      biomimetic adsorbents exhibited a higher purifying ability. Further, one
      immobilized biomimetic dye, bearing mercaptopyruvic acid as biomimetic moiety,
      displayed the highest purifying ability. The concentration of immobilized dye
      affected both the capacity and the purifying ability of the affinity column,
      exhibiting an optimum value 2.2 mumol dye/g moist gel. This affinity adsorbent
      was exploited for the purification of LDH from bovine heart in a two-step
      procedure. The procedure consisted in a biomimetic dye affinity chromatography
      step (NAD+/sulphite elution, 25-fold purification, 64% step yield), followed by
      DEAE-agarose ion-exchange chromatography (1.4-fold purification, 78% step yield).
      The purified enzyme exhibited a specific activity of ca. 480 u/mg at 25 degrees C
      (content of impurities: pyruvate kinase and glutamic-oxaloacetic transaminase
      were not detected; malate dehydrogenase, 0.01%), compared with ca. 250 u/mg of
      commercial bovine heart LDH (malate dehydrogenase, 0.05%) suitable for analytical
      purposes.

PMID- 8556166
TI  - Differences in the glycosylation of recombinant and native human milk bile salt
      stimulated lipase revealed by peptide mapping.
AB  - The milk of some mammals contains a bile salt-stimulated lipase (BSSL). Human
      milk BSSL is heavily glycosylated (30-40% carbohydrate) and present at a
      concentration of approximately 100-200 mg/l, thereby being one of the most
      abundant human whey proteins. BSSL has been shown to have an important role in
      the uptake of energy from human milk. The risk of HIV contamination has
      restricted the use of banked human milk for nutritional purposes. This has evoked
      an interest in the production of a recombinant form of the protein for
      supplementation of formula. We have produced BSSL in mouse C127 and hamster CHO
      cells, and used chromatographic methods for the characterization of the products.
      This study was focused on study of the glycosylation of the protein by using
      peptide mapping and isolation of glycosylated fragments. The results show how
      human BSSLs from different sources differ both in extent of glycosylation, in
      glycan heterogeneity, and in lectin binding.

PMID- 8556167
TI  - Elution of lipoprotein fractions containing apolipoproteins E and A-I in size
      exclusion on Superose 6 columns is sensitive to mobile phase pH and ionic
      strength.
AB  - Separation of lipoproteins secreted from McA-RH7777 (rat hepatoma) cells by
      Superose 6 column size-exclusion chromatography, using PBS buffer (NaCl 150 mM,
      sodium phosphate 10 mM, pH 7.5, EDTA 1 mM), produced apolipoprotein (apo) E or A
      I profiles that did not correlate with lipoproteins separated by density
      ultracentrifugation. By density ultracentrifugation, apoE and apoA-I were mostly
      (> 90%) confined to high-density lipoproteins (HDL, d = 1.063-1.023 g/ml), but by
      chromatography apoE and apoA-I were recovered in all lipoprotein classes,
      including low-density lipoproteins (LDL), HDL, and post-HDL. Moreover, the
      elution volume of phenol red on Superose 6 greatly exceeded the total column
      volume. These discrepancies were attributable to pH and ionic strength effects.
      In low ionic strength, high pH buffer (Tris 25 mM, pH 8.3), elution volumes of
      lipoproteins, albumin, and phenol red were minimized. Elution volumes increased
      25-70% when buffer pH was lowered at constant ionic strength (Tris 25 mM, pH 7.4)
      or when ionic strength was increased at constant pH (Tris 25 mM, pH 8.3, NaCl 500
      mM). Altered phase partition appeared to cause the altered elution volumes, since
      recovery (measured as analyte peak area), resolution (measured as peak width at
      half height), and column void volume varied little from buffer to buffer. In
      Superose 6 size-exclusion chromatography with PBS buffer, then, elution volumes
      vary with pH and ionic strength. We propose that TBE buffer (Tris-borate 89 mM,
      pH 8.3, EDTA 2 mM) may produce fewer artefacts than PBS. With TBE there were (i)
      better correlation between size-exclusion and ultracentrifugal fractions, (ii)
      lower elution volumes, and (iii) less ?smearing? of McA-RH7777 apoE and apoA-I
      containing lipoprotein bands.

PMID- 8556168
TI  - High-performance liquid chromatographic profiles of aloe constituents and
      determination of aloin in beverages, with reference to the EEC regulation for
      flavouring substances.
AB  - Characteristic HPLC profiles of fresh and aged aloe solutions, detected at 360
      and 220 nm, are presented and compared. Several aloe constituents (aloesin,
      aloeresin A, hydroxyaloin, aloin A and B and aloinoside A and B) were
      simultaneously separated and identified. The determination of aloin is described
      (detection limit 0.15 ppm) and discussed. In aloe-based alcoholic beverages, the
      aloins could not be detected, owing to their instability and degradation in
      solution; this is discussed in relation to the EEC Council Directive 88/388,
      which fixed the values of maximum allowable concentrations for aloin in food and
      beverages. Instead of aloin, other aloe compounds (e.g., aloeresin A or aloesin)
      should perhaps be used as an index of the presence of aloe in alcoholic
      beverages.

PMID- 8556169
TI  - Rationalizing antithrombotic management for patients with prosthetic heart
      valves.

PMID- 8556170
TI  - Intracardiac thrombosis: patient-related and device-related factors.

PMID- 8556171
TI  - Cardioembolism as a source of cerebrovascular events.

PMID- 8556172
TI  - Optimization of oral anticoagulation for patients with mechanical heart valve
      prostheses.

PMID- 8556173
TI  - The use of prothrombin fragment F1+2 to monitor the effect of oral
      anticoagulation.
AB  - In comparison to a control group of 47 healthy, non-anticoagulated persons, 164
      patients under stable oral anticoagulation therapy showed significant reduction
      in the plasma level of the prothrombin fragment F1+2 (p < 0.0005). Even with low
      intensity anticoagulation (INR < 2.0), F1+2 levels were reduced to within the
      normal range (0.32 - 1.2 nM/l) in all patients. The reduction in the plasma level
      of prothrombin fragment F1+2 is directly dependent on the intensity of oral
      anticoagulation therapy and provides a means of monitoring the anticoagulation
      effect achieved. Clinical studies are required to assess the practicality of
      using F1+2 for monitoring anticoagulation and in particular to assess the
      usefulness of low levels in predicting bleeding risk and high levels in
      predicting thrombotic risk during treatment.

PMID- 8556174
TI  - Prosthetic valve thrombosis.

PMID- 8556175
TI  - Thrombolytic therapy for left sided prosthetic heart valve thrombosis.
AB  - In order to clarify the role of thrombolytic therapy for the treatment of left
      sided prosthetic valve thrombosis, a composite analysis of 158 cases reported in
      the English literature was undertaken. Complete success of therapy was achieved
      in 68.4% of patients, and the results were better in patients with aortic
      compared to mitral valve prostheses (p < 0.01), in those presenting in lower NYHA
      class (p < 0.01), and with acute rather than chronic symptoms (p < 0.05). A
      successful outcome was seen more frequently with tilting disc than bileaflet
      valves (p < 0.001). Overall mortality during therapy was 7%. Cerebral embolic
      events were observed in 9.5% of patients, and irreversible neurological injury
      occurred in 4.4%. The rethrombosis rate was 17% and the incidence of late death
      was 6.3%. Thrombolysis may be a useful therapeutic alternative for left sided
      prosthetic valve thrombosis in patients with a perceived contraindication to
      surgery. The risks of systemic clot embolization along with incomplete resolution
      of valve leaflet motion or rethrombosis limits any recommendation for more
      widespread use.

PMID- 8556176
TI  - Reoperation for aortic valve periprosthetic leakage: identification of patients
      at risk and results of operation.
AB  - Periprosthetic leakage occurs in 1 to 3.5% of patients after aortic valve
      replacement. Antecedent or active infection increases the risk of perivalvular
      leakage. Other factors predisposing to perivalvular leakage have not been clearly
      identified. To determine whether clinical and/or early transthoracic
      echocardiographic features can identify patients who require reoperation for
      periprosthetic leakage, we reviewed 1,743 consecutive patients who underwent
      aortic valve replacement from 1983 through 1991. Thirty patients (1.7%)
      subsequently required repeat operation for correction of periprosthetic leakage,
      at a median of 18.0 months (range 0.5-81.0) after aortic valve replacement.
      Comparison of these 30 patients with periprosthetic leakage to those undergoing
      primary aortic valve replacement showed no differences in patient age, gender,
      native valve disease type or etiology, prosthetic valve type, or prosthetic valve
      size (all p = NS). Of the 30 patients with periprosthetic leaks, 20 had early
      postoperative transthoracic echocardiography, at a median 5.3 months (range 0.3 -
      40.0) after aortic valve replacement. In this early postoperative study, 14
      patients (70.0%) had no periprosthetic leak detectable by echocardiography; two
      patients had trivial leaks, and only four patients had significant periprosthetic
      leakage by echocardiography. During subsequent operation, aortic valve re
      replacement was performed in 26 patients (86.7%), and the periprosthetic leak was
      repaired in the remaining four patients. Thirty-day and 5-year survival
      probabilities were 0.90 (70% CI, 0.84-0.96) and 0.73 (70% CI, 0.65-0.82),
      respectively. It is concluded that in this study, there were no clinical features
      that distinguished patients undergoing aortic valve replacement who later
      developed severe perivalvular leakage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556177
TI  - Paraprosthetic regurgitation in aortic prostheses: determination of the
      hemodynamic significance by pulsed Doppler examination of the subclavian artery
      flow.
AB  - Paraprosthetic leaks in aortic prostheses may cause significant aortic
      regurgitation. Color flow Doppler echocardiography is the method of choice for
      detecting paraprosthetic leaks, but quantitation of regurgitation is limited by
      this method. This study investigated the value of pulsed Doppler of the left
      subclavian artery flow for assessing the hemodynamic significance of
      paraprosthetic regurgitation in aortic prostheses in 32 patients with, and in 77
      control subjects without paraprosthetic leaks. Paraprosthetic leaks were either
      detected by transthoracic or transesophageal color flow echocardiography. The
      hemodynamic significance of paraprosthetic regurgitation was determined by means
      of a dichotomous angiographic classification - significant versus insignificant
      regurgitation. Pulsed Doppler was performed to measure the maximal diastolic and
      systolic velocities, and diastolic and systolic velocity-time-integrals (VTI) and
      their ratios in the subclavian artery flow. The accuracy of these parameters for
      differentiating significant versus insignificant regurgitation was assessed.
      Angiography revealed 13 significant and 19 insignificant forms of aortic
      regurgitation. In all patients, examination of the subclavian artery was feasible
      by pulsed Doppler. The highest correlation between Doppler derived parameters and
      regurgitation was calculated for the ratios of diastolic and systolic VTI (r =
      0.84), diastolic VTI (r = 0.82) and ratio of diastolic and systolic velocities (r
      = 0.80). An increase of the ratio of diastolic and systolic VTI (> 45%) and ratio
      of diastolic to systolic velocity (> 0.4), and increased diastolic VTI (> 60 cm)
      in the subclavian artery velocity profile identified significant paraprosthetic
      regurgitation with a sensitivity of 94%, 75% and 87%, and specificity of 87%, 80%
      and 87%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556178
TI  - Porcine stentless aortic valve in re-replacements and acute aortic valve
      endocarditis.
AB  - Between June 1990 and June 1993, 135 patients received a porcine stentless aortic
      valve (PSAV) at our institution. In this group, there were 33 patients in whom
      the stentless valve was used to replace a previously inserted malfunctioning
      aortic valve prosthesis (n = 19) or to treat acute aortic valve endocarditis (n =
      14, five native, nine prosthetic endocarditis). There was one hospital death
      caused by multiple organ failure in a patient with endocarditis and preoperative
      cerebral stroke. Two patients died after hospital discharge; one suffered sudden
      death following a pacemaker failure four month after surgery and the other died
      due to Candida albicans sepsis after a prolonged antibiotic treatment. There were
      two reoperations; one to correct a dehiscence of the proximal suture line and the
      other to replace a degenerated valve 3.5 years after implantation in a 14 year
      old boy. All operative survivors were followed clinically with serial color
      Doppler echocardiography. No recurrence of endocarditis was detected. Aortic root
      reconstruction was achieved even in the presence of multiple abscesses. All but
      one patients showed a normally functioning valve with none or minimal aortic
      insufficiency. In our opinion the PSAV is an excellent aortic valve substitute
      for patients with damaged aortic annulus, because it promotes aortic root
      remodeling, decreases the incidence of postoperative paravalvular leaks and helps
      to prevent endocarditis recurrence.

PMID- 8556179
TI  - Regurgitation through the morphologically pulmonary valve after additional
      aortopulmonary anastomosis.
AB  - Although additional aortopulmonary anastomosis established by creating double
      outlet from the systemic ventricle and anastomosing the pulmonary trunk to the
      ascending aorta can undoubtedly provide an unobstructed outlet for the systemic
      ventricle, postoperative regurgitation of the morphologically pulmonary valve, if
      it occurs, may spoil the efficacy. To determine whether the pulmonary valve can
      be regurgitant, 11 patients undergoing this surgical option, six accompanying a
      Fontan-type operation and five associated with biventricular repair, were
      reviewed. Postoperative regurgitation was observed echocardiographically in five
      patients. One patient with severe pathologic changes of the valve showed
      progressive regurgitation, necessitating valve replacement two months after the
      aortopulmonary anastomosis. The other four patients, including one with slight
      thickening of the pulmonary leaflets, had previously undergone banding of the
      pulmonary trunk. Slight regurgitation in these cases appeared between one month
      and two years after the procedure, but then neither progressed nor regressed.
      Pathologic changes of the pulmonary valve, and previous banding, therefore, can
      be recognized as risk factors for postoperative regurgitation. The
      morphologically pulmonary valve, nonetheless, proved to be feasible for this
      surgical option unless it possessed severe organic changes.

PMID- 8556180
TI  - Pulmonary homograft insertion after repair of pulmonary stenosis.
AB  - Although the results of intracardiac repair for pulmonary stenosis or atresia are
      generally good, some patients develop symptoms due to to pulmonary regurgitation
      and right ventricular dilatation. Implantation of a pulmonary homograft may have
      a beneficial effect on these symptoms. Twenty-seven patients with symptoms due to
      pulmonary regurgitation and right ventricular dilatation were reoperated. The
      indication for surgery was dyspnea in 19, arrhythmia in five and both symptoms in
      three patients. The arrhythmia was supra-ventricular in four, ventricular in two
      and both supra-ventricular and ventricular in another two patients. A
      cryopreserved pulmonary homograft was implanted in the right ventricular outflow
      tract. Mean interval between intracardiac repair and homograft implantation was
      15.6 years. Mean age at homograft implantation was 23.0 years. Concomitant
      procedures were performed in 18 patients. There were two early deaths (7%).
      Replacement of the homograft was necessary in one patient, 21 months after
      insertion. This patient had residual pulmonary stenosis immediately after
      surgery. On mid-term follow up (mean 36 months) all patients with dyspnea as
      indication for operation improved, except one with right and left ventricular
      dysfunction. Only two of eight patients with arrhythmia improved. On
      echocardiography, pulmonary regurgitation decreased in all patients. Right
      ventricular dilatation decreased in only 14 patients (52%). We conclude that
      pulmonary regurgitation after transannular patching can be treated with
      implantation of a cryopreserved pulmonary homograft with acceptable mortality and
      low morbidity. Clinical improvement results from reduction of the right
      ventricular volume overload rather than from decline in right ventricular
      dilatation. Arrhythmia as the only indication for operation is controversial.

PMID- 8556181
TI  - Orthotopic pulmonary valve replacement with a homograft.
AB  - Eight pulmonary valve replacements (PVR) have been performed from January 1992 to
      October 1994. Three patients (mean age 7.7 years, range two to 16 years) had
      absent pulmonary valve with tetralogy of Fallot and underwent primary PVR at the
      time of surgical correction. Five other patients, who had correction of tetralogy
      of Fallot (four cases) and of double outlet right ventricle with ventricular
      septal defect and pulmonary stenosis (one case), were reoperated for pulmonary
      regurgitation with progressive right ventricular dysfunction. Mean age at the
      time of reoperation was 18 years (range seven to 34 years). There was no early
      death. Early postoperative recovery was satisfactory in all of them. The follow
      up ranges from six to 35 months (mean 19 months). Seven patients were in
      functional class I and one in functional class II when they were last evaluated
      in the out-patient department and five of them were off diuretics and
      vasodilator. In the presence of right ventricular dysfunction pulmonary
      regurgitation is poorly tolerated. A competent and non-obstructive pulmonary
      valve is often life saving in these critically ill patients.

PMID- 8556182
TI  - Use of oversized homografts for right ventricular outflow tract reconstruction in
      infants.
AB  - A surgical technique for reducing the size of large diameter homografts in order
      to make them suitable for right ventricular outflow reconstruction in infants was
      clinically introduced by us at the Department of Cardiac Surgery, University of
      Padova in 1990. The method consists of two longitudinal incisions along the
      oversized homograft root removing one cusp with the relevant part of the aortic
      annulus and aortic wall. The remaining, flat "bicuspid" homograft is closed into
      a tube again around a mandrel of appropriate size. Preliminary experiences with
      the first three patients were excellent and have already been reported. The
      current study includes five additional patients (two male, three female) ranging
      in age from 20 days to 11 months (mean 8.3 months) and in weight from 3.2 to 7.4
      kg (mean 6.2 kg) who underwent right ventricular outflow tract reconstruction
      with this surgical technique. There were no operative deaths and no instances of
      valve related complications at a mean follow up of 18 months. Serial
      echocardiography showed mild homograft stenosis in one patient (15 mmHg) and mild
      regurgitation in another. Although a longer follow up is necessary to determine
      whether the durability of these surgically modified "bicuspid homografts" can
      match that of the intact valves, we believe that our technique represents a
      valuable therapeutic alternative at least in the short term to the use of
      synthetic grafts in infants when an appropriately small homograft is not
      available.

PMID- 8556183
TI  - Mitral valve myxoma: a case report and brief review of the literature.
AB  - A case of cardiac myxoma arising from the mitral valve is reported. A 50-year-old
      woman presented with history of shortness of breath and angina. Two-dimensional
      echocardiography showed a left atrial mass. At surgery, the tumor was found to be
      arising from the anterior leaflet of the mitral valve. The tumor was excised and
      a defect in the anterior leaflet of the mitral valve was repaired by direct
      suture.

PMID- 8556184
TI  - Mitral valve tumor revealed by stroke.
AB  - Valvular tumors are uncommon and usually benign lesions, discovered accidentally
      or when neurological or cardiological complications occur. We report a case of
      mitral valve papillary fibroelastoma measuring less than 1 cm and revealed by
      stroke. Transesophageal echocardiography was the best method to establish the
      diagnosis as it provided higher discriminative power than the transthoracic
      echocardiography or nuclear magnetic resonance. The embolic risks justify the
      surgical treatment of these lesions while anticoagulation therapy can be
      suggested as a substitute to surgery for the high risk patients.

PMID- 8556185
TI  - Mitral valve repair in lupus valvulitis--report of a case and review of the
      literature.
AB  - Valvulitis in systemic lupus erythematosus has been observed for many years.
      Fourteen cases of mitral valve replacement have been reported so far in the
      literature. In the light of all previously reported experiences, prosthetic valve
      related morbidity and mortality remain high in patients with systemic lupus
      erythematosus. We describe the first true instance of reconstructive approach in
      a patient who presented with severe mitral incompetence due to lupus valvulitis.
      The patient was clinically well with good valve function one year after surgery.
      Reconstructive mitral valve surgery may be preferable for the surgical management
      of mitral regurgitation in active lupus valvulitis since it eliminates the need
      for anticoagulation and avoids the disadvantages of different types of prostheses
      in these young patients who are under prolonged steroid therapy and have usually
      associated renal failure.

PMID- 8556186
TI  - Alternative approach to the repair of a floppy anterior mitral valve leaflet.
AB  - Increased exertional dypsnea developed in a 25-year-old female with a long
      standing history of a myxomatous mitral valve. Transesophageal echocardiography
      demonstrated left atrial and ventricular dilatation and no significant functional
      impairment. In addition, there was prolapse of a voluminous anterior mitral valve
      leaflet as well as prolapse of the posterior leaflet. To avoid the risks of long
      term anticoagulation therapy including fetal teratogenicity, efforts were made to
      repair rather than replace this degenerated valve. Here we report a new technique
      of anterior or mitral valvuloplasty complementing a quadrangular resection of the
      mural leaflet and a ring annuloplasty. The elliptoid excision of the redundant
      anterior leaflet resulted in a competent valve apparatus without any significant
      gradient. This technique would not apply, however, when the chordae tendinae to
      the anterior leaflet were significantly stretched as a result of the myxomatous
      process. In that situation the valve would be replaced with a prosthesis.

PMID- 8556187
TI  - Recurrent thrombosis of Omniscience prostheses in the mitral position: a case
      report.
AB  - We report a patient who experienced thrombotic obstruction of an Omniscience
      prosthesis three years after mitral valve replacement. At reoperation another
      Omniscience prosthesis was inserted which became thrombosed after eight months.
      Recurrent thrombosis of the same prosthesis in the same patient is unusual and
      raises the problem of which device to use when replacing a thrombosed valve. In
      our patient another mechanical prosthesis was inserted at second reoperation
      because of her young age and in the hope of reducing the risk of further
      thrombosis by using a valve with better flow characteristics such as a bileaflet
      prosthesis.

PMID- 8556188
TI  - A quantitative fluoroscopic comparison of the coronary sinus ostium in patients
      with and without AV nodal reentrant tachycardia.
AB  - INTRODUCTION: The purpose of this study was to perform a quantitative
      fluoroscopic analysis of the coronary sinus ostium and its relationship to the
      His bundle in patients with and without AV nodal reentrant tachycardia. Sites of
      slow pathway ablation are often near the coronary sinus ostium, which can be
      located within a few millimeters of the His bundle. Whether such close proximity
      of the coronary sinus ostium to the His bundle is unique to patients with AV
      nodal reentrant tachycardia is unknown. METHODS AND RESULTS: Fifty consecutive
      patients (mean age 39 +/- 14 years) with no structural heart disease underwent
      electrophysiologic testing and radiofrequency ablation. The study group consisted
      of 28 patients with inducible AV nodal reentrant tachycardia or dual AV nodal
      physiology and 22 patients in the control group. A coronary sinus venogram was
      performed in each patient. The coronary sinus ostium was similar in size in the
      study group (11.4 +/- 4.5 mm) and in the control group (10.5 +/- 3.6 mm, P =
      0.2). The coronary sinus ostium was funnel shaped in half of the study patients
      and in half of the control patients (P = 1.0). The mean distance from the upper
      lip of the coronary sinus ostium to the tip of the His bundle catheter was 9.7 +/
      5.5 mm in the study group and 10.4 +/- 5.1 mm in the control group (P = 0.7).
      The mean distance from the lower lip of the coronary sinus ostium to the tip of
      the His-bundle catheter in the study group was 20.1 +/- 6.1 mm and 19.5 +/- 5.6
      mm in the control group (P = 0.7). CONCLUSION: This study demonstrates a wide
      range of normal coronary sinus ostium diameters, morphology, and anatomic
      relationships with surrounding structures, with no demonstrable correlation to
      the presence or absence of dual AV node physiology or AV nodal reentrant
      tachycardia.

PMID- 8556189
TI  - A randomized, double-blind, placebo-controlled, dose-ranging study of dofetilide
      in patients with inducible sustained ventricular tachyarrhythmias.
AB  - INTRODUCTION: Dofetilide is a new antiarrhythmic agent with potent IK blocking
      properties in vitro. We developed a dose-ranging, placebo-controlled study design
      to define the range of effective doses and to evaluate the clinical
      electrophysiology of intravenous dofetilide in patients in whom sustained
      ventricular tachycardia or fibrillation was reproducibly inducible at baseline
      electrophysiologic testing. METHODS AND RESULTS: The initial four patients
      received low doses that were increased in subsequent groups of four if adverse
      effects were absent. In each group of four patients, one patient was randomly
      assigned to placebo (double blind). Twenty-four patients were studied at six
      incremental loading and maintenance infusion regimens. Dofetilide (0.1 to 8.0
      ng/mL) produced concentration-related increases in the % delta of QT (r = 0.79, P
      < 0.001), QTc (r = 0.60, P = 0.02), RR (r = 0.62, P < 0.02), and right
      ventricular effective refractory period (cycle length 600 msec; r = 0.68, P =
      0.04). Placebo produced no changes in any of these measurements. Sustained
      ventricular tachycardia or ventricular fibrillation was no longer inducible in 1
      of 6 patients receiving placebo and 8 of 18 receiving dofetilide (4 to 13 sec
      nonsustained ventricular tachycardia was induced in 4 of these 8). One patient
      developed torsades de pointes at a high concentration (5.3 ng/mL). CONCLUSIONS:
      We conclude that: (1) dofetilide produces concentration-related IK blocking
      effects in patients; (2) an incremental dose-ranging study design aids in
      identifying the range of doses demonstrating electrophysiologic effects and
      efficacy; (3) a concomitant placebo group provides important data to assess
      reproducibility of results over time; and (4) further studies of dofetilide's
      efficacy and toxicity should be conducted.

PMID- 8556190
TI  - Comparison of atrial-His intervals during tachycardia and atrial pacing in
      patients with long RP tachycardia.
AB  - INTRODUCTION: The purpose of this study is to describe a simple and reliable
      diagnostic maneuver that allows for the rapid differentiation of atypical AV
      nodal reentrant tachycardia (AVNRT) from other causes of long RP tachycardia.
      Long RP tachycardias may be caused by atypical AVNRT, orthodromic reciprocating
      tachycardia (ORT) involving a slowly conducting retrograde accessory pathway, or
      atrial tachycardia. The differentiation of atypical AVNRT from ORT or atrial
      tachycardia may be difficult, especially when the differential diagnosis includes
      a posteroseptal accessory pathway or an atrial tachycardia arising in the
      posteroseptal right atrium. METHODS AND RESULTS: Twelve patients with atypical
      AVNRT, 21 with ORT, and 12 with an atrial tachycardia diagnosed using
      conventional criteria were enrolled in this study. The atrial-His (AH) interval
      was measured at the His-bundle position during the tachycardia and during atrial
      pacing from the high right atrium at the tachycardia cycle length in the setting
      of sinus rhythm. In patients with atypical AVNRT, the mean AH interval was 69 69
      msec +/- 50 msec (+/- SD) longer during high right atrial pacing than during the
      tachycardia (P < 0.001). In 10 of 12 patients with atypical AVNRT, the AH
      interval during atrial pacing was more than 40 msec longer than the AH interval
      measured during the tachycardia. In contrast, in patients with ORT or atrial
      tachycardia, the differences in AH interval between atrial pacing and tachycardia
      were never more than 20 and 10 msec, respectively. CONCLUSION: The difference in
      the AH interval between atrial pacing and the tachycardia allows a simple and
      rapid means of differentiating atypical AVNRT from other types of long RP
      tachycardias.

PMID- 8556191
TI  - Slowing of the ventricular rate during atrial fibrillation by ablation of the
      slow pathway of AV nodal reentrant tachycardia.
AB  - INTRODUCTION: The mechanisms whereby radiofrequency catheter modification of AV
      nodal conduction slows the ventricular response are not well defined. Whether a
      successful modification procedure can be achieved by ablating posterior inputs to
      the AV node or by partial ablation of the compact AV node is unclear. We
      hypothesized that ablation of the well-defined slow pathway in patients with AV
      nodal reentrant tachycardia would slow the ventricular response during atrial
      fibrillation. METHODS AND RESULTS: In 34 patients with dual AV physiology and
      inducible AV nodal reentrant tachycardia, atrial fibrillation was induced at
      baseline and immediately after successful slow pathway ablation and at 1-week
      follow-up. The minimal, maximal, and mean RR intervals during atrial fibrillation
      increased from 353 +/- 76, 500 +/- 121, and 405 +/- 91 msec to 429 +/- 84 (P <
      0.01), 673 +/- 161 (P < 0.01), and 535 +/- 98 msec (P < 0.01), respectively.
      These effects remained stable during follow-up at 1 week. The AV block cycle
      length increased from 343 +/- 68 msec to 375 +/- 60 msec (P < 0.05) immediately
      and to 400 +/- 56 msec (P < 0.01) at 1-week follow-up. The effective refractory
      period of the AV node prolonged from 282 +/- 83 msec to 312 +/- 89 msec and to
      318 +/- 81 msec after 1 week (P < 0.05), respectively. CONCLUSION: This study
      shows a decrease in ventricular response to pacing-induced atrial fibrillation
      after ablation of the slow pathway in patients with AV nodal reentrant
      tachycardia. Since the AV nodal conduction properties could be defined, this
      study supports the hypothesis that the main mechanism of AV nodal modification in
      chronic atrial fibrillation is caused by ablation of posterior inputs to the AV
      node.

PMID- 8556192
TI  - Effects of optical enantiomers CK-4000(S) and CK-4001(R) on defibrillation and
      enhancement of shock-induced extension of action potential duration.
AB  - INTRODUCTION: Class III antiarrhythmics have been reported to lower
      defibrillation threshold (DFT); however, the mechanism(s) of this effect is
      unknown. Recent evidence suggests that DFT strength DC shocks may terminate
      reentrant arrhythmias through prolongation of action potential duration and
      refractory periods. Since Class III antiarrhythmic drugs prolong repolarization,
      we examined the hypothesis that these drugs enhance shock-induced action
      potential duration extension (APDE), which might contribute to lowering of DFT.
      METHODS AND RESULTS: In order to investigate the specificity of drug effects on
      action potential repolarization following a shock, an optical enantiomer with
      mixed beta-blocking and Class III effects (CK-4000) and its enantiomer with
      "pure" Class III antiarrhythmic effects (CK-4001) were compared against placebo
      in a canine defibrillation model (n = 8 per group). At the 3 mg/kg dose, the
      enantiomers nonstereoselectively lowered DFT voltage by 19 +/- 15% (CK-4000, P <
      0.05 compared to placebo) and 25 +/- 12% (CK-4001, P < 0.05 compared to placebo),
      indicating that Class III antiarrhythmic actions alone were sufficient for this
      effect. Similarly, CK-4000 and CK-4001 at 3 mg/kg enhanced APDE (P < 0.01
      compared to placebo) by 20 +/- 11% and 24 +/- 17%, respectively. APDE
      prolongation significantly correlated with reduction in DFT voltage for both CK
      4000 (r = -0.55, P < 0.03) and CK4001 (r = -0.63, P < 0.01). At 3 mg/kg, the
      enantiomers stereoselectively prolonged action potential duration (APD75) by an
      average of 37 +/- 14% (CK-4000, P < 0.001) and 23 +/- 14% (CK-4001, P < 0.001),
      and ventricular effective refractory period (VERP) by 38 +/- 15% (CK-4000, P <
      0.01) and 27 +/- 13% (CK-4001, P < 0.05). Prolongations of APD75 and VERP did not
      correlate with reductions of DFT in individual dogs. CONCLUSIONS: These results
      show that Class III antiarrhythmics and DFT strength shocks additively delay
      repolarization, which suggests that drug enhancement of APDE may contribute to
      their effects on DFT.

PMID- 8556193
TI  - Electrophysiologic effects of cocaine on subendocardial Purkinje fibers surviving
      1 day of myocardial infarction.
AB  - INTRODUCTION: Cocaine has been shown to have broad cardiovascular effects that
      could be life threatening. Most of the reported electrophysiologic effects of
      cocaine have been studied in normal but not infarcted myocardium. METHODS AND
      RESULTS: Using microelectrode techniques, we investigated the electrophysiologic
      effects of cocaine on endocardial canine Purkinje fibers that survived 1 day of
      myocardial infarction. In quiescent infarcted preparations, stimulated trains
      were followed by subthreshold delayed afterdepolarizations (DADs), in the
      presence of propranolol (1 microM). Cocaine (10 microM) decreased the amplitude
      of DADs from 6.1 +/- 1.8 mV to 3.0 +/- 1.3 mV (P < 0.05, n = 6). When stimulated
      preparations (n = 23) showing no triggered activity during control (+propranolol)
      were superfused with a low concentration of caffeine (1 mM) or high extracellular
      Ca2+ (8.1 mM), triggered activity was induced. Subsequent cocaine (10 microM)
      superfusion prevented the induction of caffeine- and high Ca(2+)-induced
      triggered activity. Cocaine's effects were reversible upon washout. In
      preparations that showed triggered activity during control conditions
      (+propranolol), the mean cycle length of triggered activity was 755 +/- 45 msec.
      Cocaine (10 microM) superfusion lengthened the cycle length to 1030 +/- 141 msec
      and terminated triggered activity with a subthreshold DAD (n = 12). In addition,
      cocaine and ryanodine (10 microM) suppressed triggered activity in a similar
      manner when tested in the same preparations (n = 4). During control conditions,
      cocaine did not cause any significant change on the rate of rise of action
      potential upstroke (from 55.6 +/- 24.3 to 54.5 +/- 28.6 V/sec, n = 8) and maximum
      diastolic potential (from -58.4 +/- 4.3 to -56.6 +/- 6.5 mV, n = 8). In the
      absence of propranolol, 50 microM but not 10 microM cocaine induced early
      afterdepolarizations in 62% of the preparations exhibiting triggered activity
      during control conditions. CONCLUSION: The results suggest that cocaine modulates
      DADs and triggered activity in infarcted endocardial fibers via direct inhibition
      of cyclic release of Ca2+ from sarcoplasmic reticulum (SR) independently from a
      local anesthetic or sympathomimetic effect. This SR inhibition could account for
      the myocardial depressant effect of cocaine. However, while cocaine suppressed
      DADs, its induction of EADs can precipitate malignant ventricular arrhythmias in
      the setting of cocaine overdose and infarction.

PMID- 8556194
TI  - Choosing the optimal monophasic and biphasic waveforms for ventricular
      defibrillation.
AB  - INTRODUCTION: The truncated exponential waveform from an implantable cardioverter
      defibrillator can be described by three quantities: the leading edge voltage, the
      waveform duration, and the waveform time constant (tau s). The goal of this work
      was to develop and test a mathematical model of defibrillation that predicts the
      optimal durations for monophasic and the first phase of biphasic waveforms for
      different tau s values. In 1932, Blair used a parallel resistor-capacitor network
      as a model of the cell membrane to develop an equation that describes stimulation
      using square waves. We extended Blair's model of stimulation, using a resistor
      capacitor network time constant (tau m), equal to 2.8 msec, to explicitly account
      for the waveform shape of a truncated exponential waveform. This extended model
      predicted that for monophasic waveforms with tau s of 1.5 msec, leading edge
      voltage will be constant for waveforms 2 msec and longer; for tau s of 3 msec,
      leading edge voltage will be constant for waveforms 3 msec and longer; for tau s
      of 6 msec, leading edge voltage will be constant for waveforms 4 msec and longer.
      We hypothesized that the best phase 1 of a biphasic waveform is the best
      monophasic waveform. Therefore, the optimal first phase of a biphasic waveform
      for a given tau s is the same as the optimal monophasic waveform. METHODS AND
      RESULTS: We tested these hypotheses in two animal experiments. Part I:
      Defibrillation thresholds were determined for monophasic waveforms in eight dogs.
      For tau s of 1.5 msec, waveforms were truncated at 1, 1.5, 2, 2.5, 3, 4, 5, and 6
      msec. For tau s of 3 msec, waveforms were truncated at 1,2,3,4,5,6, and 8 msec.
      For tau s of 6 msec, waveforms were truncated at 2,3,4,5,6,8, and 10 msec. For
      waveforms with tau s of 1.5, leading edge voltage was not significantly different
      for the waveform durations of 1.5 msec and longer. For waveforms with tau s of 3
      msec, leading edge voltage was not significantly different for waveform durations
      of 2 msec and longer. For waveforms with tau s of 6 msec, there was no
      significant difference in leading edge voltage for the waveforms tested. Part II:
      Defibrillation thresholds were determined in another eight dogs for the same
      three tau s values. For each value of tau s, six biphasic waveforms were tested:
      1/1, 2/2, 3/3, 4/4, 5/5, and 6/6 msec. For waveforms with tau s of 1.5 msec,
      leading edge voltage was a minimum for the 2/2 msec waveform. For waveforms with
      tau s of 3 msec, leading edge voltage was a minimum for the 3/3 msec waveform.
      For waveforms with tau s of 6 msec, leading edge voltage was a minimum and not
      significantly different for the 3/3, 4/4, 5/5, and 6/6 msec waveforms.
      CONCLUSIONS: The model predicts the optimal monophasic duration and the first
      phase of a biphasic waveform to within 1 msec as tau s varies from 1.5 to 6 msec:
      for tau s equal to 1.5 msec, the optimal monophasic waveform duration and the
      optimal first phase of a biphasic waveform is 2 msec, for tau s equal to 3.0
      msec, the optimal duration is 3 msec, and for tau s equal to 6 msec, the optimal
      duration is 4 msec. For both monophasic and biphasic waveforms, optimal waveform
      duration shortens as the waveform time constant shortens.

PMID- 8556195
TI  - Cardiac pacing during neurocardiogenic (vasovagal) syncope.
AB  - Head-up tilt testing is increasingly being used as a diagnostic modality in
      patients with unexplained syncope who are thought to have neurocardiogenic
      (vasovagal) mechanisms of syncope. Although large-scale placebo-controlled trials
      are still awaited, pharmacologic therapy is usually effective in preventing
      syncope or presyncope in this patient population. However, the role of permanent
      pacemaker therapy remains controversial. Because hypotension is usually
      associated with paradoxical bradycardia and occasionally asystole, it has been
      argued that permanent pacemaker therapy may be useful in preventing syncope and,
      thus, injury, in the so-called "malignant vasovagal cardioinhibitory response" in
      which the onset of syncope is thought to be abrupt. The onset of hypotension,
      however, usually precedes bradycardia during neurocardiogenic syncope, and pacing
      may thus not prevent syncope or presyncope in these patients. The role of cardiac
      pacing in patients with neurocardiogenic syncope is reviewed.

PMID- 8556196
TI  - Baroreflex sensitivity.
AB  - Baroreflex sensitivity (BRS) has rapidly gained considerable attention as a
      result of multiple experimental and clinical reports on its prognostic value
      after a myocardial infarction. This article reviews the several aspects related
      to the use and significance of BRS. The methodology of baroreflex testing in man
      is described. The complex pathophysiology underlying BRS and the hypotheses
      proposed to explain its frequent reduction after a myocardial infarction are
      discussed. The section on experimental data also provides a rationale to
      understand the relation between increased vagal activity and reduced propensity
      for ventricular fibrillation. The article focuses largely on the clinical studies
      relating BRS and risk of cardiac mortality and also discusses the several
      attempts to modify this marker of reflex vagal activation.

PMID- 8556197
TI  - [Sheltered living. A possibility of reintegration of chronic addicts].

PMID- 8556198
TI  - [Which pizza do you like best? Playful initiation of contact with children].

PMID- 8556199
TI  - [Relational aspects in psychiatric care. Why are there uniforms?].

PMID- 8556200
TI  - [Housing and restraint. Unlawful restriction of personal freedom].

PMID- 8556201
TI  - [Surgical spirits--an application ritual?].

PMID- 8556202
TI  - [Primary health care. Primary health care or medical care system].

PMID- 8556203
TI  - [From the breach to the bridge. Transfer of nursing supervision from the hospital
      to ambulatory care or nursing home].

PMID- 8556205
TI  - [Powerless care].

PMID- 8556204
TI  - [Reformer of German nursing. Agnes Karll and the civic women's movement].

PMID- 8556206
TI  - Science and antiscience in complementary medicine.

PMID- 8556207
TI  - Alcohol and life expectancy.

PMID- 8556208
TI  - The team approach to percutaneous endoscopic gastrostomy feeding.
AB  - The importance of early recognition and treatment of patients who are at risk of
      developing malnutrition is becoming increasingly recognised. Percutaneous
      endoscopic gastrostomy has become increasingly popular as a method of feeding,
      since its description in 1980, because of its ease of insertion and low morbidity
      and mortality. Its success, however, depends upon the use of a multidisciplinary
      approach.

PMID- 8556209
TI  - Anorexia nervosa and the heart.
AB  - Anorexia nervosa is an eating disorder which predominantly affects young females.
      A variety of cardiovascular complications are described. These include
      lengthening of the QT interval and other electrocardiographic abnormalities,
      reduced left ventricular mass and impaired myocardial performance, mitral valve
      prolapse and sudden death. The incidence of these abnormalities and their
      relation to outcome are discussed in this article.

PMID- 8556210
TI  - Phaeochromocytoma.
AB  - Phaeochromocytomas are rare catecholamine-secreting tumours which can mimic a
      variety of common clinical conditions, such as hypertension and angina. It is a
      potentially curable condition if discovered early, and clinicians should be
      alerted as to its presence in a young individual with hypertension or atypical
      angina-associated hypertension. Pharmacological mismanagement can cause fatal
      hypertensive crisis.

PMID- 8556211
TI  - Khat chewing as a cause of psychosis.
AB  - It is well established that psychosis may arise in the context of abuse of
      certain illicit drugs (e.g. amphetamine). This article reviews the effects of
      chewing the plant khat and outlines the pharmacological aspects, the dependence
      issue and a comparative study between previously reported cases and four cases
      reported here to highlight the epidemiology, clinical features and prognosis of
      khat-induced psychosis.

PMID- 8556212
TI  - Infant nutrition. Part 2: Weaning-1 year.
AB  - The weaning process is vital for infants, not only from the nutritional point of
      view, but also in establishing normal feeding habits. This article describes the
      accepted pattern of weaning and the reasons behind the nutritional and
      behavioural problems that commonly arise.

PMID- 8556213
TI  - Diagnosis and treatment of nosocomial pneumonia.
AB  - Nosocomial pneumonia (NP) occurs frequently and is associated with increased
      morbidity and mortality. Its diagnosis, however, is difficult. The combination of
      clinical, radiographical and microbiological criteria may overestimate the true
      incidence of the infection. Although recently introduced techniques, such as
      bronchoscopy, probably increase the specificity for diagnosing NP, it remains to
      be established whether the use of these techniques improves patient outcome or
      decreases unnecessary antibiotic use.

PMID- 8556214
TI  - Prevention of infective endocarditis: enthusiasm tempered by realism.
AB  - Infective endocarditis is a cause of substantial morbidity and mortality, and
      antibiotic prophylaxis may be appropriate in some circumstances. This article
      examines current British recommendations on prophylaxis, circumstances in which
      it may be beneficial and evidence for its efficacy.

PMID- 8556215
TI  - Heterotopic pregnancy associated with assisted conception.

PMID- 8556216
TI  - Finance in the NHS for doctors.
AB  - A trust finance director argues that doctors are best placed to win the debate on
      better health care for all, but first must understand the realities of being part
      of central government and the financial consequences of this. Change will best be
      achieved by facing up to the financial issues and moving the system from within;
      clinical audit could prove to be the most powerful weapon.

PMID- 8556217
TI  - A painting that changed by my life.

PMID- 8556218
TI  - Cerebral palsy and the use of suxamethonium.

PMID- 8556219
TI  - A pre-eclamptic with coarctation of the aorta.

PMID- 8556220
TI  - Reference tables for the intrasubject coefficient of variation in bioequivalence
      studies.
AB  - Bioequivalence studies are usually performed as crossover studies and, therefore,
      information on the intrasubject coefficient of variation is needed for sample
      size planning. However, this information is usually not accessible in
      publications on bioequivalence studies, and only the pooled inter- and
      intrasubject coefficient of variation for either test or reference formulation is
      reported. It is the purpose of the present communication to provide reference
      values of the intrasubject coefficient of variation for various previously
      investigated drugs. The presentation includes pertinent pharmacokinetic
      characteristics for immediate- and extended-release formulations in single- and
      multiple-dose crossover studies.

PMID- 8556221
TI  - Bioequivalence evaluation of two different oral formulations of loperamide
      (Diarex Lactab vs Imodium capsules).
AB  - Twenty-four healthy male volunteers were treated with two different oral
      formulations of loperamide according to a randomized two-way cross-over design.
      The test preparation was Diarex Lactab (Mepha), the reference preparation Imodium
      2 mg capsules. Divided in two periods the volunteers received single 8 x 2 mg (=
      16mg) doses of the test and reference formulation, respectively. Blood samples
      were taken immediately prior to each administration and at 14 points within 60 h
      after the dose. A wash-out period of 1 week was interpaused between successive
      drug doses. The plasma concentration of the pharmacologically active compound,
      loperamide, was determined by HPLC with electrochemical detection. The
      calibration function was linear in the range 0-10.0 ng/ml. A lower limit of
      quantification of 0.2 ng/ml was established. The pharmacokinetic parameters Cmax
      and tmax were obtained directly from plasma data. The elimination constant was
      estimated by log-linear regression of the measured concentrations in the terminal
      phase. AUC was calculated by the trapezoidal rule and extrapolated to infinity.
      The following mean values were obtained after intake of 16 mg loperamide as film
      coated tablets: AUC0 infinity 62.04 ngh/ml, Cmax 3.35 ng/ml, tmax 4.08 h, t1/2
      19.66 h and after administration of the capsules: AUC0 infinity 66.56 ngh/ml,
      Cmax 3.98 ng/ml, tmax 4.38 h, t1/2 18.43 h. The pharmacokinetic parameters AUC0
      infinity and Cmax were tested for bioequivalence parametrically (two one-sided t
      tests) after logarithmic transformation of data. Differences of tmax were
      evaluated non-parametrically. The preparations were found to be bioequivalent
      and, therefore, interchangeable.

PMID- 8556222
TI  - Prescribing patterns in primary health care in Taiwan.
AB  - To identify the prescribing patterns in public group practice centers (GPCs),
      84,453 prescription sheets written by primary care physicians in 168 GPCs during
      the period from December 7-12, 1992, were collected and analyzed. The average
      number of drugs per script was 4.3 and the ratio of drug to total medical expense
      was 44%. The 5 most common diagnoses were, in a descending order, upper
      respiratory tract infection, skeletomuscular and joint disease, hypertension,
      functional gastrointestinal disorder (including peptic ulcer) and diabetes
      mellitus. The top 5 most commonly dispensed drug categories were antacids and
      anti-ulcer drugs, anti-cough and anti-cold preparations, vitamins, simple
      analgesics and non-steroidal anti-inflammatory drugs, accounting for 48.8% of
      total prescriptions. In view of the frequency of relevant diagnoses, the overuse
      of antacids, vitamins, intravenous nutrient and electrolyte solutions, anti-cold
      preparations and antibiotics was apparent, as was that of drugs of questionable
      pharmacological value. These data indicate that polypharmacy is a widespread
      phenomenon and confirms our long-term concern over irrational drug use in GPCs in
      Taiwan. Both administrative and educational intervention should be implemented to
      improve prescribing quality at the primary health care level.

PMID- 8556223
TI  - The bioavailability of intramuscularly administered nicomorphine (Vilan) with its
      metabolites and their glucuronide conjugates in surgical patients.
AB  - The kinetics of 20 mg nicomorphine intramuscularly were described in 8 patients
      under combined general and epidural anesthesia. The half-life of nicomorphine was
      0.32 +/- 0.20 h (mean +/- SD) and is governed by the absorption-rather than the
      elimination rate. The half-life of 6-mononicotinoylmorphine (0.39 +/- 0.09 h) was
      identical to that of the parent compound (p = 0.29), suggesting it is directly
      related to the absorption rate of nicomorphine. Morphine had a half-life of 1.38
      +/- 0.31 h. Morphine is subsequently metabolized into morphine-3-glucuronide and
      morphine-6-glucuronide. The half-life of these 2 glucuronide conjugates was about
      2.6 h (p = 0.07). A glucuronide conjugate of 6-mononicotinoylmorphine was not
      detected. In urine only morphine and its glucuronides are found, with renal
      clearance values of 214 ml.min-1 for morphine and 132 ml.min-1 for the
      glucuronides. The bioavailability of this pharmaceutical formulation after
      intramuscular administration equals that of intravenous administration in
      surgical patients (at the same dose).

PMID- 8556224
TI  - Protein binding of itraconazole and fluconazole in patients with cancer.
AB  - The serum protein binding of itraconazole and fluconazole, new azole antifungal
      agents, has been investigated in vitro, in serum from healthy volunteers and from
      patients with cancer. Protein binding was determined by ultrafiltration.
      Concentrations of both alpha 1-acid glycoprotein (AAG) and albumin (HSA) were
      measured in all serum samples. The serum protein binding of itraconazole was
      reduced in patients (96.02 +/- 1.41% vs 97.25 +/- 0.54%; p < 0.01) with respect
      to healthy volunteers. In contrast, fluconazole protein binding was increased in
      the same group of patients (22.96 +/- 3.60% vs 13.30 +/- 2.58%; p < 0.01). HSA
      levels in cancer patients were significantly decreased (p < 0.01) and AAG levels
      were found to be significantly elevated in patients with respect to control
      subjects (p < 0.05). A significant linear relationship between the bound/unbound
      concentration ratio of itraconazole and HSA (r2 = 0.3340; p < 0.01) was found.
      Similarly, a significant relation was established between the bound/unbound
      concentration ratio of fluconazole and AAG levels (r2 = 0.2235; p < 0.05). Thus,
      a weak association between the binding of these drugs and serum protein levels
      has been observed. It is concluded that both antifungal drugs show different
      protein binding behaviour in cancer patients.

PMID- 8556225
TI  - Ketanserin effects on insulin sensitivity in nonobese, nondiabetic hypertensive
      patients: an evaluation by the euglycemic-hyperinsulinemic clamp technique.
AB  - The aim of this study was to assess the effects of ketanserin on insulin
      resistance in nondiabetic hypertensive patients. Eleven nonobese, nondiabetic
      mild to moderate hypertensives (6 males, 5 females, aged 39-59 years), after a 4
      week run-in period on placebo, were treated with ketanserin 40 mg twice daily for
      12 weeks. Blood pressure (BP) (by standard mercury sphygmomanometer) and insulin
      sensitivity (by the euglycemic hyperinsulinemic clamp technique) were evaluated
      at the end of the placebo period and at the end of the treatment period.
      Ketanserin produced a significant decrease in BP (from 160 +/- 13/100 +/- 4 mmHg
      to 146 +/- 10/89 +/- 5 mmHg p < 0.01). The amounts of exogenous glucose required
      to hold glucose levels constant during clamp were not changed by ketanserin as
      compared to placebo 34.5 +/- 3.5 g vs 33.8 +/- 3.1 g). The rate of glucose
      infusion required during the last 60 minutes of the clamp, used as an indicator
      of insulin sensitivity, was not different before and after treatment (5.52 +/-
      0.41 mg/min/ kg vs 5.21 +/- 0.39mg/min/kg). These results suggest that in
      nonobese, nondiabetic hypertensive patients ketanserin monotherapy is effective
      in reducing BP values without affecting insulin sensitivity.

PMID- 8556226
TI  - Studies of natural killer cell activity in a drug-free, healthy population.
      Response to a challenge with taxol, estramustine and lipopolysaccharide.
AB  - Preincubation of peripheral blood lymphocytes with the microtubule disturbing
      agents estramustine (ETMN; n = 7, final conc. 20 microM) or taxol (TX; n = 13,
      final conc. 10 microM), resulted in a statistically significant inhibition of
      natural killer cell activity [(NKCA); baseline (x +/- SD; expressed as percentage
      of specific chromium release) of 32.2 +/- 30.5 and 34.4 +/- 27.7 and drug treated
      samples of 13.9 +/- 19.9 and 12.5 +/- 20.8, respectively; Student's paired t-test
      p < 0.005]. Furthermore, most individual values for NKCA in the drug preincubated
      samples were at least 20% below the same subject baseline lytic function (except
      for TX sample No.1), and NKCA was non detectable in 4 out of 7 and 5 out of 13
      samples (pretreatment with either ETMN or TX< respectively). The use of other
      concentrations and different preincubation times for these chemotherapeutic
      agents also produced NKCA inhibition, which was time and dose dependent.
      Preincubation with lipopolysaccharide (LPS; n = 16, final conc. 50
      micrograms/ml), an endotoxin prominently involved in the etiology of septic
      shock, resulted in a statistically significant enhancement of NKCA [baseline (x
      +/- SD; expressed as percentage of specific chromium release) of 25.4 +/- 20.4
      and LPS treated sample of 36.6 +/- 17.4, respectively; Student's t paired t-test
      p < 0.005]. At least a 20% increase in NKC lytic function over its own baseline
      value was recorded for each and everyone of the samples tested with LPS.2+ the
      pathophysiology associated with septic shock.

PMID- 8556227
TI  - Influence of ethanol ingestion on tetracycline kinetics.
AB  - The effect of ethyl alcohol ingestion on tetracycline kinetics was studied in 9
      healthy male volunteers. They received, on two separate occasions, 500 mg of
      tetracycline tablets given with water or with an alcoholic beverage. The
      antibiotic was assayed in plasma, using a HPLC method. Absorption and disposition
      parameters were calculated according to classical pharmacokinetic techniques for
      one compartment model. The significance of changes in pharmacokinetic parameters
      was determined by a multiway ANOVA test. In the present study, ingestion of
      alcohol caused significant increase of Cmax (from 9.317 to 12.362 micrograms/ml),
      and increase of AUC (from 62.65 to 94.28 micrograms/ml*h).

PMID- 8556228
TI  - Adjuvant therapy with 5-fluoro-1-(2-tetrahydrofuryl)-2,4 (1H,3H)-pyrimidinedione
      (UFT) and Bestatin in patients with transitional cell carcinoma of the bladder-
      comparison between UFT therapy alone and UFT therapy in combination with
      Bestatin.
AB  - To prevent postoperative recurrence a randomized prospective trial was performed
      on 45 patients with bladder cancers by dividing them into 2 groups given either
      UFT therapy alone or UFT therapy in combination with Bestatin. In principle, oral
      administration of these drugs was initiated 4 weeks postoperatively and continued
      for a period of 1 year. Bestatin was given at the dose of 30 mg/day after
      breakfast per os, and UFT at the dose of 400 mg/day twice a day per os. After a
      median follow-up period of 628 days the relapse-free rate was 43.5% for the group
      given UFT alone and 81.8% for the group given a combination of UFT plus Bestatin,
      showing a significantly more favorable result in the latter group. In patients
      with a solitary and papillary tumor the relapse-free rate was significantly
      better in the UFT plus Bestatin group compared with the group of UFT alone.
      Accordingly, it was suggested that postoperative administration of UFT in
      combination with Bestatin is more effective in preventing recurrence of bladder
      cancer, compared with the administration of UFT alone.

PMID- 8556229
TI  - IUPHAR guidelines for classification of new receptor-subtypes.

PMID- 8556230
TI  - Proceedings of the British Pharmacological Society meeting. 12-14 July 1995.
      Abstracts.

PMID- 8556231
TI  - A three-component model for magnetization transfer. Solution by projection
      operator technique, and application to cartilage.
AB  - A projection-operator technique is applied to a general three-component model for
      magnetization transfer, extending our previous two-component model [R.S. Adler
      and H.N. Yeung, J. Magn. Reson. A 104, 321 (1993), and H.N. Yeung, R. S. Adler,
      and S.D. Swanson, J. Magn. Reson. A 106, 37 (1994)]. The PO technique provides an
      elegant means of deriving a simple, effective rate equation in which there is
      natural separation of relaxation and source terms and allows incorporation of
      Redfield-Provotorov theory without any additional assumptions or restrictive
      conditions. The PO technique is extended to incorporate more general,
      multicomponent models. The three-component model is used to fit experimental data
      from samples of human hyaline cartilage and fibrocartilage. The fits of the three
      component model are compared to the fits of the two-component model.

PMID- 8556232
TI  - Resolved two-dimensional anisotropic-chemical-shift/heteronuclear dipolar
      coupling powder-pattern spectra by three-dimensional solid-state NMR
      spectroscopy.

PMID- 8556233
TI  - Amino-acid-type-selective triple-resonance experiments.

PMID- 8556234
TI  - A sensitive HN(CA)CO experiment for deuterated proteins.

PMID- 8556235
TI  - A 23Na multiple-quantum-filtered NMR study of the effect of the cytoskeleton
      conformation on the anisotropic motion of sodium ions in red blood cells.
AB  - Recently, it has been shown that 23Na double-quantum-filtered NMR spectroscopy
      can be used to detect anisotropic motion of bound sodium ions in biological
      systems. The technique is based on the formation of the second-rank tensor when
      the quadrupolar interaction is not averaged to zero. Using this method,
      anisotropic motion of bound sodium in human and dog red blood cells was detected,
      and the effect was shown to depend on the integrity of the membrane cytoskeleton.
      In the present study, multiple-quantum-filtered techniques were applied in
      combination with a quadrupolar echo to measure the transverse-relaxation times,
      T2f and T2s. Line fitting was performed to obtain the values of the residual
      quadrupolar interaction, which was measured for sodium in a variety of mammalian
      erythrocytes of different size, shape, rheological properties, and sodium
      concentrations. Human unsealed white ghosts were used to study sodium bound at
      the anisotropic sites on the inner side of the RBC membrane. Modulations of the
      conformation of the cytoskeleton by the variation of either the ionic strength or
      pH of the suspending medium caused drastic changes in both the residual
      quadrupolar interaction and T2f due to changes in the fraction of bound sodium
      ions as well as changes in the structure of the binding sites. By combining the
      two spectroscopic parameters, structural change can be followed. The changes in
      the structure of the sodium anisotropic binding sites deduced by this method were
      found to correlate with known conformational changes of the membrane
      cytoskeleton. Variations of the medium pH affected both the fraction of bound
      sodium ions and the structure of the anisotropic binding sites. Sodium and
      potassium were shown to bind to the anisotropic binding sites with the same
      affinity.

PMID- 8556237
TI  - Phosphorus J coupling constants of ATP in human myocardium and calf muscle.
AB  - Proton-decoupled 31P NMR spectroscopy of the heart and calf muscle of healthy
      volunteers was performed with a 1.5 T whole-body imager. By use of two
      dimensional chemical-shift imaging in combination with slice-selective
      excitation, well-resolved localized spectra (elements of 38 ml) were obtained
      within 20 to 35 min from which the homonuclear J coupling constants of ATP could
      be determined. In myocardium, J gamma beta = 16.03 +/- 0.17 Hz and J alpha beta =
      15.82 +/- 0.23 Hz were obtained, while the values in calf muscle were J gamma
      beta = 17.16 +/- 0.12 Hz and J alpha beta = 16.04 +/- 0.09 Hz. The difference in
      J gamma beta was significant. According to the literature, a possible reason for
      greater ATP J coupling constants is a smaller fraction of ATP complexed to
      magnesium. However, the chemical-shift difference between alpha- and beta-ATP,
      which is also a measure for the fraction of ATP complexed to magnesium, showed
      only a small difference in ATP complexation: 88% in myocardium and 90% in calf
      muscle. This small difference cannot account for the observed difference in J
      gamma beta.

PMID- 8556236
TI  - Cross-correlation effects on NMR lineshapes and peptide conformation.
AB  - Information about molecular structure and dynamics can potentially be obtained by
      studying dipole-dipole and chemical-shift anisotropy (CSA) auto-correlation and
      dipole-CSA cross-correlation effects in high-resolution NMR spectra. Equations
      for the lineshapes of the HN multiplet in the fragment- 15NH-CH- as a function of
      NH-CH dihedral angle are derived by including these effects within the framework
      of the Redfield treatment of relaxation. To test the utility of the theoretical
      results, 1H[15N] HSQC proton lineshape data for a variant of the enzyme
      staphylococcal nuclease in which all valine residues are labeled with 15N have
      been analyzed to obtain the conformational angle (phi) between the N-H and
      adjacent C-H bonds. The results are generally in good agreement with values of
      phi obtained from crystal structure data. Considerations in the further
      development of the analysis of the lineshape of the HN multiplet for experimental
      determinations of phi are discussed.

PMID- 8556238
TI  - ANDANTE, a novel frequency-selective adiabatic pulse.

PMID- 8556239
TI  - Improved proton assignment for DNA by application of aliasing and dispersive
      absorptive phasing to two-quantum COSY spectra.
AB  - A unique combination of aliasing and dispersive-absorptive (DA) phasing of two
      quantum correlated spectroscopy (2 Q-COSY) NMR data is shown to enhance proton
      chemical-shift assignments in DNA oligonucleotides by (i) reducing the time
      necessary for acquiring NMR data or, alternatively, improving the spectral
      resolution in a given time, (ii) reducing the number of spectra necessary for NMR
      data processing and analysis, and (iii) increasing the complexity of
      oligonucleotide sequences and structures which are accessible to 2D NMR analysis.
      Aliasing allows a reduction in the size of the acquired data without significant
      risk of losing information. Phasing the 2Q-COSY dispersive in the F2 dimension
      reduces the primary antiphase doublet into a pseudo-singlet and increases the
      apparent signal-to-noise. A single 2Q-COSY spectrum can provide an amount of
      chemical-shift information comparable to that from a series of COSY, relayed
      COSY, and/or spin-lock COSY spectra optimized for various coupling constants. The
      low signal-to-noise inherent in the most popular two-quantum-filtered correlated
      spectroscopy (2QF-COSY) of samples with naturally broad lines is largely avoided
      due to less cancellation. There is no diagonal in a 2Q-COSY which can obscure
      correlations between protons which are nearly isochronous. As an example of this
      efficient application, the assignment of 139 of the 143 proton resonances from a
      single 2Q-COSY and a 2D-NOE spectrum of the DNA hexadecamer
      [d(AAATATAGCTATATTT)]2 is demonstrated.

PMID- 8556240
TI  - Water exchange filter with improved sensitivity (WEX II) to study solvent
      exchangeable protons. Application to the consensus zinc finger peptide CP-1.

PMID- 8556241
TI  - [The importance of serotyping Plesiomonas shigelloides].
AB  - The author presents an account of serovars of 432 strains of Plesiomonas
      shigelloides from various countries and sources; in addition to strains from man
      and animals also environmental strains. The most frequent serovars are O17 with
      three H antigens (H2, H11, H34) except for immobile strains, also O32:H4 and non
      motile strains, O2:H1a1c and O44:H8. The other serovars did not reach the number
      of 10 strains, some serovars were found only one strain of each. Serovar O18:H2
      was isolated in the course of 30 years only from cats and lynx and once from a
      pond in the FRG. As regards the distribution of different serovars, e.g. O68:H2
      was found only in one district, while strains of the serogroup O17 come from
      various countries in the world. Between findings of the same serovar sometimes a
      20-30-year interval elapses.

PMID- 8556242
TI  - [Incidence of sepsis in the Czech Republic. Analysis of mortality in 1993].
AB  - Sepsis holds the second place on the list of deaths from infectious diseases.
      Epidemiological data on the morbidity from sepsis are inadequate. The basis of
      the submitted paper are data from the Czech Statistical Office on subjects who
      died of sepsis, death certificates and health records. The analysis of assembled
      data pertains to 85 subjects who died from sepsis in 1993 and is concerned with
      the age distribution of the deceased, the distribution by gender, type of
      hospital department, where death occurred, and the diagnosis made on admission. A
      group of 32 subjects who developed a septic focus during hospitalization (group
      of nosocomial sepses) was investigated further: 10 developed a decubital sepsis
      (31%), 3 a diabetic sepsis and 5 urosepsis. As to risk factors, in addition to
      ATB therapy the following dominated: repeated hospitalizations, the development
      of infectious decubiti, infusions and venous and urinary catheters. A
      haemoculture was examined in 9 (28%), 4 times Gram-positive cocci were detected,
      5 times Gram-negative rods. Antibiotics were prescribed to two-thirds of the
      affected patients: gentamicin in 35%, ampicillin in 34%, PNC in 13%, cefotaxime
      in 12% of the affected subjects.

PMID- 8556243
TI  - [Mobilization of genetic determinants of antibiotic resistance in strains of
      Pseudomonas aeruginosa].
AB  - The authors describe a phenomenon of mobilisation of antibiotic resistance from
      non-transferring strains of P. aeruginosa by cultivation with strains of P.
      aeruginosa capable to transfer determinants of antibiotic resistance to a
      susceptible recipient strain, by triparental cross. In this report three strains
      of P. aeruginosa (No. 282, 283 from Bata's Hospital in Zlin and 76 from Frankfurt
      University Clinics) are described capable to mobilise for transfer the resistance
      determinants in four strains of P. aeruginosa (No. 76, 229, 47 and 125 from
      Frankfurt University Clinics) with multiple antibiotic resistance which itself
      was not transferable to recipient strains. By an indirect selection method it was
      assessed, that all six antibiotics (cephalotin-cefazoline, carbenicillin,
      kanamycin, cefotaxime, ceftazidime and aztreonam), present in resistance spectrum
      of intermediary recipient strains, were mobilised for transfer. Imipenem and
      ofloxacin were not mobilised for transfer. In the second and third cycles of
      transfer the authors confirmed the stability and transferability of the block of
      six antibiotic resistance determinants, which were not previously transferable.

PMID- 8556244
TI  - [Seroprevalence of anti-hepatitis A antibodies in Czech soldiers serving in U.N.
      forces--suggestions for a hepatitis A vaccination schedule].
AB  - Viral hepatitis A is a frequent disease particularly in developing countries. All
      workers and UN forces (UNO) are vaccinated against VHA with Havrix vaccine. The
      Czech units which were and are engaged on the territory of former Jugoslavia are
      not yet vaccinated against this contagious disease. The main purpose of the
      present study was to assess the immunity rate of VHA among Czech soldiers of the
      UN forces before their departure to the site of action. Another objective was to
      assess a suitable vaccination procedure. Sera were examined by the MEIA method
      (Microparticle Enzyme Immunoassay) in a fully automated IMx system in the
      Military Health Institute, Ceske Budejovice. For investigation HAVAB kits of
      Abbott Co. were used. A total of 667 serum samples were assembled, 19 had to be
      discarded because of small amounts (less than 50 microliters or because of
      haemolysis. The positive titre of "total" antibodies was set at 35 mIU anti-HAV;
      thus a total of 648 specimens were examined in 1991 - 1994 (1991 - 65, 1992 -
      296, 1993 - 265, 1994 - 22). Of these 249 (38.4%) were positive and 399 (61.6%)
      were negative. The examined subjects were divided into four age groups (20 - 29,
      30 - 39, 40 - 49, 50 - 59), the approximate distribution being 23%, 50%, 25%, 2%.
      The ratio of negative and positive specimens in different age groups was 1:0.3,
      1:0.6, 1:1, 1:2.7. The seroprevalence of anti-HAV antibody increases from 25.3%
      in the first age group, in the second one it is 37.9%, in the third one 49.5% and
      72.7% in the last age group, i.e. in the age bracket of 50 - 59 years. The
      results indicate a very low immunity rate in the lower age brackets and the
      necessity to vaccinate them before they depart. It is beyond doubt that it pays
      to examine the soldiers for the presence of total anti-HAV and immunize only
      subjects with a negative antibody titre. The vaccination approach Havrix 2 x 720
      EU was recommended.

PMID- 8556245
TI  - [The effect of subinhibitory concentrations of quinolone and macrolide
      antibiotics on production of thermolabile hemolysins in Pseudomonas aeruginosa].
AB  - The authors investigated the effect of subinhibitory concentrations (sub-MICs) of
      selected quinolones (enoxacine, nalidixic acid, norfloxacine) and macrolid
      antibiotics (erythromycin, roxitromycin) on the production of thermolabile
      haemolysin (phospholipase C) of P. aeruginosa. The activity of phospholipase C
      was markedly reduced by norfloxacine (more than 80%) and enoxacine (75 - 80%) in
      all sub-MICs. Nalidixic acid inhibited phospholipase C in 1/4 of MIC (75%). As to
      macrolid antibiotics the greatest inhibition was caused by erthromycin in 1/4 and
      1/8 MIC (more than 90%). 1/16 MIC of roxitromycin did not influence the activity
      of the investigated enzyme and other tested sub-MICs caused its reduction to cca
      one half.

PMID- 8556246
TI  - [Seroprevalence of IgG antibodies against parvovirus B19 in the population of the
      Czech Republic].
AB  - The human parvovirus B 19 was discovered in 1975 by Cossart in England. Later
      (1984) evidence was provided that this virus is the etiological agent of erythema
      infectiosum and hydrops foetalis, and in 1985 it was provided that it is also the
      etiological agent of some types of arthritis or arthropaties and vasculitis. The
      diagnosis of the disease caused by this agent is most frequently based on
      evidence of specific immunoglobulins. The epidemiological and clinical impact of
      parvoviral infections in the Czech Republic was not known so far. Examination of
      sera from 562 subjects aged 0-60 years assembled in 1992 in three Czech regions
      revealed in children, age 0 - 4 years 9.8%, during preschool and school age 27 -
      35.7% and in age groups above 15 years a 53.3 - 57.7% seroprevalence of IgG
      parvovirus B 19, roughly equally distributed among both sexes. The more frequent
      prevalence of specific immunoglobulins was proved in small groups of female
      workers in nurseries (66.7%), nursery schools (91.7%) and in blood transfusion
      stations (77.8%). The seropositivity of the general female population of matched
      age groups, with the exception of women aged 20 - 24 years, was 53.86%.

PMID- 8556247
TI  - [Zoonotic dermatomycoses in urban populations].
AB  - The authors analyzed epidemiologically two cases of trichophytosis caused by
      zoophilic dermatophytes in persons living in the city. The first case was a male
      aged 43, suffering from trichophytosis on the right side of his neck. The patient
      was infected at work from guinea pigs. Trichophyton mentagrophytes varietas
      granulosum was the etiological agent. The second case occurred in a female aged
      29, suffering from trichophytosis on her left arm. Trichophyton verrucosum was
      the causal agent. A horse was the source of infection.

PMID- 8556248
TI  - [Is the present trend in cardiovascular disease mortality in the Slovak Republic
      a reason for optimism?].
AB  - The authors analyzed the cardiovascular mortality trend in 1985 - 1990 and 1991 
      1994. They discuss factors which may have influenced this trend which declined
      slightly since 1991. They emphasize the importance of cardiovascular diseases in
      public health and ask epidemiologists, health professionals and the public to pay
      more attention to the elimination of risk factors of cardiovascular diseases. The
      authors' suggestions are in context with some countries which made already
      considerable advances as regards elimination of cardiovascular risk factors.

PMID- 8556249
TI  - [Modern ethical problems in environmental epidemiology].
AB  - The author presents a summary account on the session of the International
      workshop on ethical and philosophical issues in environmental epidemiology
      convened by the Rome Division of ECEH WHO and the International Society for
      Environmental Epidemiology (North Carolina, USA, Sept. 16-18, 1994). Twenty-one
      epidemiologists and workers concerned with ethics and philosophy from Europe,
      North America and other regions were invided. The subject of discussion was a
      definition of the discipline of environmental epidemiology and concurrently
      ethical and philosophical problems of the discipline. It was stated that it is
      essential to adopt ethical guidelines in the sphere of environmental
      epidemiology. It was recommended that, where reliable safeguards of processed
      personal data exist, access to the pertinent databases could be granted without
      previous informed consent of probands. Informed consent must be obtained only in
      later stages of research if direct contact with the individual subject is
      essential. Recommendations were adopted for practitioners, universities and
      training centres, professional organizations and institutions as well as sponsors
      interested in environmental epidemiology. It was emphasized that efforts to
      improve ethical awareness and practice must become and integral part of training
      and practical activities of all concerned.

PMID- 8556250
TI  - [The present status of prevalence of infections against which regular
      immunization is provided in the Czech Republic].

PMID- 8556251
TI  - Stump the experts.

PMID- 8556252
TI  - Dermabrasion for prophylaxis and treatment of actinic keratoses.
AB  - BACKGROUND: After dermabrasion, patients with actinic keratoses remain free of
      new lesions for many years. This clinical effect has been alluded to for 40 years
      in the dermatologic literature. However, there has been no consensus on how long
      this clinical benefit actually lasts. OBJECTIVE: To ascertain the longevity of
      the beneficial effect of dermabrasion, clinical records of patients who underwent
      this procedure for treatment of actinic keratosis were reviewed. METHOD:
      Retrospective review. RESULTS: A total of 23 such patients with at least 2 years
      good clinical follow-up were identified. Their ages ranged from 33 to 76 years.
      One year after dermabrasion, 96% remained free of new actinic keratoses. The
      benefits of dermabrasion gradually diminished with 83% clear at 2 years, 79% at 3
      years, 64% at 4 years, and 54% at 5 years. The average time after dermabrasion
      before the appearance of one actinic keratoses was 4 years (median, 4.5 years).
      Dermabrasion, however did not prevent the appearance of basal cell carcinomas in
      the perinasal area. CONCLUSION: Dermabrasion provides long-term effective
      prophylaxis against actinic keratoses and presumably squamous cell carcinomas.
      The benefits last for an average of 4 years before even one new actinic keratosis
      reappears. Cryosurgery, 5-Fluorouracil, and chemical peels result in much shorter
      prophylaxis. Dermabrasion is the most effective modality for prevention of new
      actinic keratoses.

PMID- 8556253
TI  - Delayed full-thickness grafting of lower leg defects following removal of skin
      malignancies.
AB  - BACKGROUND: Closure of wounds on the lower leg can be difficult. If primary
      closure of local flap repair cannot be accomplished, grafting is usually the next
      option. Full-thickness grafts are, generally superior to split-thickness grafts,
      but may not survive immediate postoperative grafting on the lower leg. OBJECTIVE:
      The purpose of this report is to demonstrate another approach to treatment of
      lower leg wounds. METHODS: Thirteen patients with lower leg wounds were
      successfully closed with a delayed full-thickness skin graft. CONCLUSION: This
      study demonstrates that delayed full-thickness grafting of the lower extremities
      may have advantages over other methods.

PMID- 8556254
TI  - The postauricular cutaneous advancement flap for repairing ear rim defects.
AB  - BACKGROUND: Due to the ear's complicated anatomy and closely adherent anterior
      skin, repairing ear rim defects is often difficult. OBJECTIVE: We describe a
      simple postauricular cutaneous advancement flap for correcting ear rim defects of
      varying sizes. METHODS: Skin tumors involving the ear rims of 12 patients were
      excised. A postauricular cutaneous advancement flap was designed to correct the
      resulting defects. RESULTS: The postauricular cutaneous advancement flap provided
      excellent cosmetic results in our 12 patients. Minimal superficial necrosis of
      the flap was observed in one patient. CONCLUSION: Utilizing relatively loose
      postauricular skin, this postauricular advancement flap can cover helical rim
      defects of varying sizes with excellent cosmetic results and low complication
      rates.

PMID- 8556255
TI  - Treatment of telangiectasia macularis eruptiva perstans with the 585-nm flashlamp
      pumped dye laser.
AB  - BACKGROUND: Telangiectasia macularis eruptiva perstans (TMEP) is a form of
      cutaneous mastocytosis characterized by truncal telangiectases that are
      refractory to treatment. OBJECTIVE: The safety and efficacy of treating TMEP with
      laser surgery was tested in a patient with extensive truncal lesions. METHODS:
      The patient was treated with the 585-nm flashlamp-pumped dye laser.
      Diphenhydramine and ranitidine or doxepin were used pre- and postoperatively to
      block the effects of mast cell mediator release during surgery. RESULTS: All
      treated cutaneous lesions resolved completely, without scarring, after one
      treatment. Approximately 70% of the truncal lesions recurred 14 months
      postoperatively. Doxepin provided the best mast cell mediator blockade.
      Postoperative biopsy of a treated lesion demonstrated focal dermal vascular
      fibrosis with minimal telangiectasia and upper level of normal numbers of mast
      cells on the biopsy. CONCLUSIONS: An excellent therapeutic result was obtained by
      treating TMEP with the 585-nm flashlamp-pumped dye laser, although the response
      was temporary. The therapeutic effect of the laser appears to be secondary to
      reduction of the vasculature with no apparent effect on the mast cells.
      Physicians treating TMEP with laser therapy must use proper H1 and H2 receptor
      blockade to avoid potential complications from laser-induced mediator release.

PMID- 8556256
TI  - Cosmetic denervation of the muscles of facial expression with botulinum toxin. A
      dose-response study.
AB  - BACKGROUND: Botulinum toxin has been used for facial hemispasm, strabismus, and
      blepharospasm. Recently it has been advocated to treat the frown lines. We have
      extended this program to treatment of other muscles of facial expression.
      METHODS: Botulinum toxin is injected into the muscles of facial expression in two
      or three sessions to produce a temporary loss of muscle tone. A standard method
      of cooling, injection, and compression was developed to minimize pain and
      bruising. OBJECTIVE: To complete a dose-response study to document the optimum
      timing and amount of toxin needed for each muscle group. RESULTS: Two to five
      Botulinum toxin units per muscle was as adequate as higher doses. Toxin that was
      reconstituted 30 days earlier produced the same loss of muscle tone as freshly
      mixed toxin. With two or three injection sessions loss of muscle tone lasted for
      up to 1 year. CONCLUSION: Botulinum toxin is highly effective as an adjuvant
      therapy for facial rejuvenation. This minor surgical procedure can temporarily
      reduce the lines on the upper face and produce a pleasing effect. With proper
      dosing and dilution this rejuvenation program becomes cost effective.

PMID- 8556257
TI  - Scalp flaps in the treatment of baldness. Long-term results.
AB  - BACKGROUND: Scalp flaps have been used as a treatment for male pattern baldness
      for many years. OBJECTIVE: To assess the long-term results of these flaps.
      METHODS: Twenty patients who underwent a total of 31 temporo-parieto-occipital
      and temporo-parietal flaps 10-20 years ago were reviewed. RESULTS: Consistent
      maintaining of the initially obtained coverage and a low incidence of
      complications was demonstrated. Universally, the male pattern baldness
      progressed, requiring in some patients subsequent procedures. CONCLUSIONS: Scalp
      flaps, when performed properly with anticipation of further hair loss, are an
      effective treatment of male pattern baldness in the appropriately selected
      patient.

PMID- 8556258
TI  - Ambulatory phlebectomy. A rare complication of local anesthetic: case report and
      literature review.
AB  - BACKGROUND: Full-thickness skin necrosis can occur after infiltration of 1.0%
      lidocaine with 1/100,000 epinephrine for ambulatory phlebectomy. OBJECTIVE: To
      demonstrate an exaggerated local response to epinephrine resulting in full
      thickness skin necrosis and ultimately a permanent scar. METHODS: A postoperative
      complication was clinically observed. CONCLUSION: Permanent scar formation after
      ambulatory phlebectomy was found in a patient with a previous probable
      exaggerated local response to epinephrine. Uneventful phlebectomy resulted in the
      same patient when epinephrine was deleted from the local anesthetic, suggesting a
      local inability to eliminate epinephrine or an exaggerated local alpha-one
      response.

PMID- 8556259
TI  - The femoropopliteal vein. Ultrasound anatomy, diagnosis, and office surgery.
AB  - BACKGROUND: The femoropopliteal vein (FPV) is evidenced by several anatomic and
      phlebographic studies, but its pathology and treatment are not sufficiently
      described in clinical and surgical textbooks. OBJECTIVE: To raise awareness of
      the existence of the FPV and describe its anatomy, involvement in varicose vein
      disease, diagnosis, and treatment. METHODS: Literature review and description of
      12 illustrative cases diagnosed by duplex ultrasound. In six patients the FPV was
      avulsed by ambulatory phlebectomy. RESULTS: Duplex scan allows easy diagnosis and
      precise marking of the incompetent FPV and permits its avulsion by stab incision
      phlebectomy. CONCLUSIONS: The FPV is a specific anatomic vein with standard
      relations to other anatomic structures and may become involved in varicose vein
      disease. FPV incompetence escapes clinical diagnosis but is easily detected by
      duplex ultrasound. The incompetent FPV can be avulsed by ambulatory phlebectomy
      (Muller technique) in an office setting under local infiltration anesthesia.

PMID- 8556260
TI  - An ambulatory treatment of varicose veins associating surgical section and
      sclerotherapy of large saphenous veins (3S technique). Preliminary study with
      results at one year.
AB  - BACKGROUND: The 3S technique enables treatment of large incontinent greater
      saphenous veins in patients who, for medical or social reasons, refuse
      traditional surgical methods. It associates phlebectomy with section-ligation and
      injection of a sclerosing solution in the proximal and distal segments. The 3S
      technique is merely one stage in the treatment of the saphenous vein, aimed at
      suppressing reflux, and associated with sclerosis of the junction. It must always
      be combined with later sclerotherapy sessions. METHODS: One hundred and eight
      patients were operated on by the 3S technique, of which 100 had 1-year follow-up.
      Each patient was checked by duplex scan examination before treatment, and 1 month
      and 1 year after. RESULTS: We obtained good results without reflux in 96% at the
      sapheno-femoral junction at 1 year. CONCLUSIONS: Superficial venous insufficiency
      is a chronic disease with evolution or recurrences. To appreciate the efficiency
      of 3S technique, it will be better to have 5 years worth of follow-up. This is a
      preliminary study with a short follow-up.

PMID- 8556261
TI  - Hyaluronidase in the prevention of sclerotherapy-induced extravasation necrosis.
      A dose-response study.
AB  - BACKGROUND: A previous study found hyaluronidase to be effective in the
      prevention of necrosis following intradermal sodium tetradecyl sulfate and 23.4%
      sodium chloride. There are no published dose-response studies of hyaluronidase
      used in this manner. OBJECTIVE: To conduct a dose-response study using
      hyaluronidase in the prevention of necrosis following intradermal 23.4% sodium
      chloride. METHODS: Study I evaluated control vs hyaluronidase groups (150, 300,
      450 units; all in volume of 3 mL) in the prevention of necrosis following
      intradermal 0.25 mL 23.4% sodium chloride. Incidence and size of necrosis were
      compared between groups. In study II, hyaluronidase was administered in doses
      ranging from 18.75 to 900 units (all in volume of 3 mL) immediately following the
      intradermal instillation of 0.25 mL of 23.4% sodium chloride. A control group had
      no therapy. The incidence of necrosis was compared between groups. A dose
      response curve was constructed. Both studies were randomized and blinded and used
      Sprague-Dawley rats. RESULTS: A statistically significant protective effect was
      found in the treated vs the untreated groups in both studies. Maximal protection
      was achieved by 75 units of hyaluronidase and was not improved upon by higher
      doses. CONCLUSION: In the event of extravasation with 23.4% sodium chloride, in
      the model studied, one can expect maximal protection with a dose of 75 units of
      hyaluronidase.

PMID- 8556262
TI  - Treatment of small bleeding varicose veins with injection sclerotherapy. Bleeding
      blue blebs.
AB  - BACKGROUND: Bleeding is a well-recognized but seemingly uncommon complication of
      varicose vein disease. Some deaths have occurred in which bleeding developed from
      vessels in the base of chronic venous ulcers. OBJECTIVE: To elucidate a more
      common type of venous bleeding that can be identified and treated by an
      experienced sclerotherapist. METHODS: The records of a group of patients with
      bleeding superficial phlebectasias, primarily on the feet and ankles, are
      reviewed. All patients received injection sclerotherapy after the initial
      bleeding episode. A comparison was made between those patients whose bleeding
      points were sutured in the emergency department and those who were treated only
      with compression. RESULTS: Suture-ligation of the bleeding site delayed healing
      when compared with simple compression. Concomitant injection sclerotherapy proved
      to be a successful and permanent method of treating these veins. No recurrent
      bleeding developed in any of the patients, even in those with previous episodes
      of bleeding. CONCLUSIONS: Initial treatment of the bleeding blue bleb requires
      only compression of the tiny open vessel. Later injection sclerotherapy provides
      a permanent method of obliterating the thin-walled veins and prevents future
      bleeding. It is essential to treat the entire incompetent venous system as well
      as the bleeding site itself.

PMID- 8556263
TI  - Cellular blue nevus with massive regional lymph node metastases.
AB  - BACKGROUND: Small, well-differentiated groups of nevus cells have been found
      occasionally in the marginal sinuses and parenchyma of regional lymph nodes that
      drain sites of cellular blue nevi. OBJECTIVE: The histologic,
      immunohistochemical, and karyometric description of a pigmented cutaneous lesion,
      with the features of cellular blue nevus and located on the leg of a 14-year-old
      woman, that was accompanied by synchronic presentation of massive inguinal lymph
      node metastases. METHODS: The excised specimens were processed routinely,
      embedded in paraffin, and sectioned into 4-microm-thick slices. The sections were
      stained using hematoxylin-eosin and the ABC immunohistochemical method for
      demonstrating S-100 and HMB-45. Karyometric analysis was performed in a static
      cytometer using Feulgen-stained sections. RESULTS: The cutaneous lesion had the
      cytologic and architectural features of cellular blue nevus. The lymph nodes
      showed massive invasion by pigmented cells and contained extensive necrotic foci.
      After 3.5 years of clinical follow-up, the patient is free from disease.
      CONCLUSIONS: The absence of malignant features in the cutaneous lesion and the
      bland nuclear features of the pigmented cells in the regional lymph node
      metastases suggest that this case could be interpreted as an unusual form of
      benign cellular blue nevus with metastases. Nonetheless, other possibilities,
      such as malignant melanoma mimicking a cellular blue nevus or primary malignant
      melanoma of the lymph nodes with concomitant cutaneous cellular blue nevus,
      cannot be definitively excluded. A conservative surgical approach with close
      follow-up was recommended.

PMID- 8556264
TI  - Tattoo pigment mimicking metastatic malignant melanoma.
AB  - BACKGROUND: The benefits of elective lymph node dissection (ELND) in the
      treatment of melanoma remain controversial, however, it may be beneficial in some
      patients. Tattoo pigment from decorative tattoos may migrate to the regional
      lymph nodes. In patients who develop malignant melanoma and who have been
      tattooed, this pigment may clinically mimic metastatic disease. OBJECTIVE: We
      wish to alert clinicians that pigment from tattoos may migrate to the regional
      lymph nodes. In the unusual instance of a tattooed patient who develops malignant
      melanoma, when undergoing ELND, surgeons should rely on histologic confirmation
      of metastatic disease before altering operative plans. METHODS: ELND for
      malignant melanoma, in a patient with a history of decorative tattoos that had
      been removed by dermabrasion, was performed. Black lymph nodes that clinically
      resembled metastatic disease were identified. Subsequent histologic examination
      revealed normal lymph node architecture with a heavy collection of black pigment.
      Mass spectrophotometry showed this pigment to be consistent with tattoo dye.
      RESULTS: A patient who had undergone dermabrasion for removal of decorative
      tattoos developed malignant melanoma in the same extremity. Clinically suspicious
      black lymph nodes were identified during ELND. Histologic examination did not
      reveal metastatic disease. Additional therapy was not considered intra- or
      postoperatively even though the clinical suspicion of metastatic disease was
      high. The patient was not subjected to any unnecessary emotional or physical
      distress pending histologic confirmation. CONCLUSIONS: Tattoo pigment in the
      lymph nodes may clinically mimic metastatic melanoma. Histologic confirmation of
      metastatic disease should always be obtained before additional therapy is
      considered.

PMID- 8556265
TI  - Diagnostic problems of desmoplastic melanoma in a boy with xeroderma pigmentosum.

PMID- 8556266
TI  - The relationship between basal cell carcinoma and cigarette smoking.

PMID- 8556267
TI  - Hair restoration: answered questions.

PMID- 8556268
TI  - Chemical modulation of 5-HT3 and 5-HT4 receptors affects the release of 5
      hydroxytryptamine from the ferret and rat intestine.
AB  - In species which vomit, elevated intestinal serotonin (5-hydroxytryptamine, 5-HT)
      may stimulate abdominal vagal afferent fibers, which in turn evoke the vomiting
      reflex. The release of 5-HT from intestinal enterochromaffin (EC) cells is
      regulated by polymodal mechanisms. The object of this study was to evaluate the
      involvement of 5-HT autoreceptors in the regulation of 5-HT release from the
      small intestine. Functional studies were carried out using 5-HT3 receptor agonist
      and antagonists, and 5-HT4 receptor agonist. Ferret and rat ileal tissue were
      isolated and 5-HT released into the bathing solution was determined using HPLC
      with an electrochemical detector (ECD). We previously reported that cisplatin
      produced a significant increase in cumulative 5-HT release and that ondansetron,
      a selective 5-HT3 receptor antagonist, did not alter the 5-HT release from the
      ferret ileum. In this study, a selective 5-HT3 agonist, 2-methyl-5-HT, induced a
      dose-dependent increase of 5-HT from the rat ileum. This release of 5-HT was
      significantly reduced by granisetron, a selective 5-HT3 receptor antagonist.
      Furthermore, a selective 5-HT4 receptor agonist, 5-methoxytryptamine induced a
      concentration-dependent increase of 5-HT in the rat ileum. These results suggest
      that both 5-HT3 and 5-HT4 receptors may be involved in intestinal 5-HT release.

PMID- 8556269
TI  - Effect of intracerebroventricular and intrahypothalamic administrations of
      picrotoxin on basal and stimulated gastric acid secretion.
AB  - The effects of intracerebroventricular and intrahypothalamic injections of
      picrotoxin, a GABA antagonist, on gastric acid secretion were studied in perfused
      stomachs of rats under anesthesia. Injection of picrotoxin into the lateral
      cerebroventricle inhibited the 2-deoxy-D-glucose-stimulated acid secretion. In
      experiments of intrahypothalamic injections, picrotoxin produced a significant
      depression of 2-deoxy-D-glucose-stimulated acid secretion when administered to
      the ventromedial hypothalamus but not to the lateral hypothalamus. In contrast,
      picrotoxin produced a definite stimulatory effect on basal acid secretion when
      injected to the lateral hypothalamus or ventromedial hypothalamus; the
      stimulatory effect of the injection to the lateral hypothalamus was greater than
      that of the injection to the ventromedial hypothalamus. These findings indicate
      that picrotoxin acts centrally, probably hypothalamus, to depress the 2-deoxy-D
      glucose-stimulated acid secretion. On the other hand, blockade of GABA activity
      in the lateral hypothalamus or ventromedial hypothalamus may elicit gastric acid
      secretion. These results, indicate that central GABAergic mechanism is important
      in regulating gastric acid secretion in the rat.

PMID- 8556270
TI  - Phosphatidylinositol 3-kinase inhibitor, wortmannin, inhibits 5-hydroxytryptamine
      mediated potentiation of platelet aggregation induced by epinephrine.
AB  - The role of phosphatidylinositol 3-kinase (PI 3-kinase) was investigated in human
      platelets exposed to varying doses of 5-hydroxytryptamine (5-HT) and subthreshold
      doses of epinephrine. The synergistic effect of 5-HT on epinephrine-induced
      aggregation was blocked by a specific inhibitor of PI 3-kinase, wortmannin, in a
      dose-dependent manner. However, there was no effect of inhibitors of protein
      kinase A (PKA) or protein kinase C (PKC). These studies suggest a role of PI 3
      kinase in the 5-HT induced potentiation of epinephrine-mediated platelet
      aggregation.

PMID- 8556271
TI  - Pharmacokinetic and tissue distribution changes of adriamycin and adriamycinol
      after intravenous administration of adriamycin to alloxan-induced diabetes
      mellitus rats.
AB  - The pharmacokinetic and tissue distribution changes of adriamycin (ADM) were
      investigated after intravenous (i.v.) administration of ADM, 16 mg/kg, to the
      control rats and alloxan-induced diabetes mellitus rats (AIDRs). After 1 min i.v.
      infusion of ADM, apparent 'constant' plasma levels of ADM were maintained from 2
      to 12 h in the AIDRs, whereas the levels were detected only up to 3 h in the
      control rats. Adriamycinol was detected only up to 1 and 5 min for the control
      rats and AIDRs, respectively, with significantly higher levels in the AIDRs. In
      tissue distribution studies, the amount of ADM obtained from the heart, lung,
      stomach, liver, small intestine, large intestine, fat, and lymph nodes were
      significantly higher in the AIDRs than that in the control rats. The tissue to
      plasma ratios of the liver, fat, and muscle also increased significantly in the
      AIDRs than those in the control rats. The amount of adriamycinol obtained from
      the lung, kidney, and liver was significantly higher in the AIDRs. All 7 control
      rats survived longer than 48 h, however 7 out of 9 AIDRs died between 36-48 h
      after i.v. administration of ADM, suggesting that the i.v. doses. of ADM in
      diabetes mellitus patients may need to be modified if the present rat data could
      be extrapolated to human.

PMID- 8556272
TI  - A study of collagen-hyaluronan interaction through swelling in polyacrylamide
      gels.
AB  - The equilibrium swelling of biopolymer loaded polyacrylamide gels can yield
      information on polymer-polymer interactions. Using the temperature dependence of
      excess equilibrium swelling, equations were derived to yield homopolymer as well
      as heteropolymer interactions. Hyaluronan and collagen (Type I) encapsulated in
      polyacrylamide gels showed increasing isothermal swelling with increase in the
      bipolymer concentration. The pH dependence of isothermal swelling caused by
      hyaluronan indicated that the swelling was largely due to repulsion of the
      charges of the carboxylate groups. Temperature dependent studies showed a
      decrease in swelling with an increase in temperature for collagen. The opposite
      trend was found for hyaluronan. This indicates that the interactions among
      collagen monomers are largely hydrophobic, while the interactions among
      hyaluronan molecules are mainly hydrogen bonding and repulsive ionic forces.
      Combined hyaluronan and collagen in polyacrylamide gels demonstrated an increase
      in swelling with an increase in temperature albeit much reduced compared with
      hyaluronan alone. Collagen interacts with hyaluronan through ionic attraction.

PMID- 8556273
TI  - Zinc promotes the repair of wounded monolayers of cultured vascular endothelial
      cells.
AB  - The effect of zinc on the repair of wounded monolayers of bovine aortic
      endothelial cells in a culture system was investigated. It was morphologically
      found that zinc promotes the appearance of the cells in the wounded area; cell
      number in the area was significantly increased by zinc. However, other heavy
      metals including copper, manganese, nickel and cobalt failed to exhibit a similar
      effect. The repair induced by exogenous basic fibroblast growth factor (bFGF) was
      potentiated by zinc but that by exogenous acidic fibroblast growth factor was
      unaffected by the metal. Promotion of the repair of the wounded area by zinc was
      completely blocked by either cycloheximide or anti-bFGF antibody. In addition,
      zinc-induced repair was significantly inhibited by a lipoxygenase inhibitor,
      nordihydroguaiaretic acid but not by a cyclooxygenase inhibitor, indomethacin.
      From these results, it is suggested that zinc promotes the repair process of
      damaged vascular endothelium through the lipoxygenase pathway that mediates the
      response of vascular endothelial cells to endogenous bFGF.

PMID- 8556274
TI  - Relative zinc-binding capacity of metallothionein in hepatic cytosols of zinc
      injected rats.
AB  - In order to determine the zinc-binding capacity of metallothionein in hepatic
      cytosols of zinc-injected rats, we examined the relationship between zinc
      contents in cytosols and metallothionein fraction in rat livers. Each rat was
      injected intraperitoneally once with 0.9% NaCl or zinc (10, 20, 40 or 60 mg
      zinc/kg b.w.) and was killed 14 h after injection. The distribution profiles of
      the hepatic cytosols of zinc-injected rats on a Sephadex G-75 column showed that
      the increased zinc was attributable to the metallothionein and high molecular
      weight proteins. Our results demonstrated that 63% of the increased zinc in
      hepatic cytosols of zinc-injected rats was bound to metallothionein and that 23%
      of the increased zinc was bound to high molecular weight proteins. These results
      suggest that the mechanisms of zinc accumulation in rat liver are different from
      those of cadmium accumulation.

PMID- 8556275
TI  - Prevention of myocardial infarction by vitamin B6.
AB  - Vitamin B6 is effective in the treatment of carpal tunnel syndrome and related
      disorders in patients with vitamin B6 deficiency. Hyperhomocysteinemia, a risk
      factor for atherosclerosis, is associated with deficiencies of vitamin B6,
      folate, and cobalamin. Patients who were given vitamin B6 for carpal tunnel
      syndrome and other degenerative diseases were found to have 27% of the risk of
      developing acute cardiac chest pain or myocardial infarction, compared with
      patients who had not taken vitamin B6. Among elderly patients of the author (JE)
      expiring at home, the average age at death from myocardial infarction was 8 years
      later in those who had taken vitamin B6, compared with those who had not taken
      vitamin B6. The preventive effect of vitamin B6 on progression of coronary heart
      disease may be related to increased formation of pyridoxal phosphate, the
      coenzyme that is required for catabolism of the atherogenic amino acid,
      homocysteine.

PMID- 8556276
TI  - Disordered copper metabolism in LEC rats, an animal model of Wilson disease:
      roles of metallothionein.
AB  - Disordered copper (Cu) metabolism in LEC rats, an animal model of Wilson disease,
      was characterized by specifying Cu in the liver, bloodstream and kidneys during
      the accumulation process and at the onset of jaundice; Cu accumulates in the
      liver with age in a form bound to metallothionein (MT). Massive Cu is liberated
      from MT when Cu accumulates beyond the capacity of MT synthesis. Cu bound to MT
      is not supplied to ceruloplasmin (Cp) during its maturation process, while the
      metal is transferred to Cu,zinc (Zn)-superoxide dismutase (SOD) directly from MT.
      Cu ions not bound to MT are transferred to Cp and the holo-Cp is excreted into
      the bloodstream near and at the onset of jaundice. Cu accumulated in the liver in
      a form bound to MT is removed selectively by tetrathiomolybdate (TTM), and the
      animal at the beginning of the onset of jaundice recovers by the chelation
      therapy. Mechanisms of the removal reaction were proposed to involve formation of
      MT/TTM, Cu/TTM, and/or polymeric Cu/TTM complexes according to the stoichiometry
      of TTM to Cu. The Cu/TTM complex was assumed to be effluxed into the bloodstream
      and to bind specifically to albumin. TTM is taken up by the liver in accordance
      with the Cu content. The toxicity of Cu was explained by the active oxygen
      species produced in Cu-mediated reactions, and the participation of MT.

PMID- 8556277
TI  - Tracking the in vivo localization of streptococcal cell membrane (SCM) monoclonal
      antibodies: potential model for post-streptococcal sequelae.
AB  - Placement of ten different anti-streptococcal monoclonal antibody (mAb) secreting
      hybridoma cells, as well as positive and negative controls into animals and
      sacrificing on a daily basis showed a difference in the tissue sites of
      accumulating mAb as noted by fluorescent antibody testing. Initial binding of the
      mAb was noted by day two on the kidney GBM in all the animals. Striated muscle
      tissues tested positive starting at day nine with only four of the mAbs, by which
      time the GBM was strongly positive. Fluorescent antibody testing of heart and
      skeletal muscle from animals in which one of the polyreactive IgM mAb secreting
      hybridoma cell lines was placed showed a distinctive staining of the Z-lines.
      Indirect fluorescent and immunoperoxidase testing as well as competitive blocking
      experiments confirmed the reactivity of this mAb for the Z-line of heart and
      skeletal muscle. Immunodots and Western blots along with direct and blocking
      assays confirmed that the critical cross-reactive Z-line antigen was alpha
      actinin, supporting the concept that this anti-SCM mAb was reactive both in vivo
      and in vitro. These results confirm the cross-reactive nature of anti-SCM
      antibodies for mammalian tissue and bear important implications on the etiology
      of post-streptococcal glomerulonephritis and rheumatic heart disease.

PMID- 8556278
TI  - Second malignant neoplasms in children with retinoblastoma: the St. Jude
      Children's Research Hospital experience.
AB  - A retrospective review of 172 children with primary diagnosis of retinoblastoma
      (RB) was completed at St. Jude Children's Research Hospital to evaluate the
      incidence of second malignant neoplasm (SMN) development. Sixty-five patients
      presented with bilateral RB and 107 with unilateral RB. During follow-up, which
      ranged from 6 to 340 months (median = 170 months), 6 children (3.5%) developed
      SMN. All patients who developed SMN presented with bilateral disease (n = 5) or
      asynchronous bilateral disease (n = 1); two patients had a family history of RB.
      All had received irradiation. Four patients developed osteogenic sarcoma within
      this irradiated volume, one developed a basal cell carcinoma in the temporal
      region (within the irradiation field), and one was diagnosed with a lower
      extremity Ewing's sarcoma. Time to development of SMN ranged from 125 to 194
      months post-irradiation. Initial irradiation total dose ranged between 32 and
      45.76 Gy. Three patients were treated with anterior field irradiation and three
      received lens-sparing techniques (anterior/lateral n = 2, lateral n = 1). At last
      follow-up, 4/6 patients had died of SMN. The crude incidence is 3.5% with an
      estimation of risk using the density method of 24% at 20 years for SMN
      development. The specifics of the treatment associated with these second
      malignancies and the possible reasons for the reported incidence of SMN will be
      discussed.

PMID- 8556279
TI  - Asynchronous bilateral retinoblastoma: the St. Jude Children's Research Hospital
      experience.
AB  - Between May 1962 and July 1993, 172 children presented at the St. Jude Children's
      Research Hospital for evaluation and/or treatment of retinoblastoma (RB). Of
      these, 65 presented with bilateral disease, while 107 had unilateral tumors. Of
      these 107 patients, nine subsequently developed RB in the unaffected eye. Initial
      age at diagnosis of these nine patients ranged from 3 weeks to 24 months (median
      = 2 months); five of the nine had a family history of RB at the time of initial
      diagnosis and one patient, without a family history of RB, presented with
      unilateral multiple tumors indicating inheritance of a germinal mutation and
      increased risk of RB development in the companion eye. Time to development of
      companion eye RB was 1-61 months postinitial diagnosis. Treatment of the initial
      eye included enucleation (n = 4), chemotherapy (n = 3), irradiation (n = 7), or a
      combination of these three modalities. Reese-Ellsworth grouping of the companion
      eye disease included I A (n = 7), III A (n = 1), and IV A (n = 1). Treatment of
      the second affected eye included irradiation in seven patients, cryotherapy in
      four, and chemotherapy in three. No companion eye has required enucleation to
      date. At last followup, 14/18 eyes remain intact. There have been no cases of
      metastatic dissemination; however, one patient has developed a second malignant
      neoplasm outside the field of irradiation. Eight of the nine patients remain
      alive. This experience reinforces the need for close follow-up of patients
      diagnosed with unilateral RB, especially those with a family history of RB and
      those with unilateral multiple tumors.

PMID- 8556280
TI  - X-linked retinitis pigmentosa: re-evaluation of fundus findings and the use of
      haplotype analysis in clarification of carrier female status.
AB  - The identification by fundus examination of those females carrying an X-linked
      retinitis pigmentosa (RP) gene can reportedly be as high as 87%. In genetic
      counselling sessions with young females with a 50% risk of being a carrier who
      wished to know their status, it has not been possible to achieve such a level of
      success. A review and reanalysis of previous reports indicated that if a tapetal
      like reflex was not present in those age 35 years or less, the likelihood of
      identifying a carrier by fundus examination was small. A family with 7 females
      with a 50% risk of being a carrier of X-linked RP was evaluated using haplotype
      analysis in an attempt to identify the X chromosome carrying the RP gene. In the
      family described, it was possible to establish that a mutation in the RP3 locus
      most likely causes the disease. This has permitted the determination of the
      carrier status in each of the females with a high degree of certainty.

PMID- 8556281
TI  - Neurological disorders in members of families with Leber's hereditary optic
      neuropathy (LHON) caused by different mitochondrial mutations.
AB  - Neurological abnormalities have been occasionally associated with Leber's
      hereditary optic neuropathy (LHON). We describe four patients with spastic
      dystonia from two of our 35 LHON families. Magnetic resonance imaging revealed
      signal alterations of globus pallidus, putamen, internal capsula, and substantia
      nigra. Neuropathological findings in one of the patients with dystonia are
      described. Each of the dystonia families carries a different mtDNA mutation; one
      at np 3460 and one at np 11778. Periventricular multiple sclerosis-like white
      matter lesions were observed in one individual from a third family with the mtDNA
      3460 mutation. Neurological disorders are probably underestimated in association
      with LHON.

PMID- 8556282
TI  - Clinical features and molecular genetics of Von Hippel-Lindau disease.
AB  - Although familial cancer syndromes are rare, a knowledge of these disorders is
      relevant to both clinicians and basic scientists. This is exemplified by Von
      Hippel-Lindau (VHL) disease which is caused by germline mutations in the VHL
      tumour suppressor gene. This multisystem disorder provides a complex clinical
      problem for ophthalmologists and other specialists. In addition, recent advances
      in the molecular genetics of this disorder are providing novel insights into the
      molecular mechanisms of tumourigenesis in VHL disease and in more common
      nonfamilial neoplasms such as clear cell renal carcinoma and central nervous
      system haemangioblastoma. In this review, we describe the clinical manifestations
      (with particular reference to the ocular complications) and the molecular
      genetics of VHL disease.

PMID- 8556283
TI  - Transgenic models for eye malformations.
AB  - Several lines of transgenic mice developing eye malformations have been described
      in the literature and appear to be of increasing interest for the study of eye
      teratology in humans, since gene expression and regulation can be studied in the
      developing animal. Transgenic applications are briefly described here and an
      overview of existing transgenic mouse models carrying different eye abnormalities
      is given according to the major diagnosis (e.g., cataract, microphthalmia,
      anterior segment dysgenesis, retinal dysplasia). Interestingly, many transgenic
      models exhibit pathological findings similar to those observed in human pediatric
      ophthalmology. Unfortunately, detailed embryological studies in transgenic mice
      bearing congenital eye malformations are not available for all lines. Thus, the
      importance of creating further transgenic models to study the function of
      morphogenes and growth factors in eye development is also discussed.

PMID- 8556284
TI  - 1995 World Congress on Psychiatric Genetics. Cardiff, United Kingdom, 29 August-1
      September 1995. Abstracts.

PMID- 8556285
TI  - Why rationing is on the agenda.
AB  - The National Health Service Act of 1946 set out to provide a comprehensive health
      service, free at the point of use, to the whole population of the UK. The purpose
      as Nye Bevan, then Minister of Health, put it-was to ensure that nobody should be
      denied, on the grounds of lack of means, 'the best that medical skill can
      provide'. Among the many fears about the Act voiced at the time, the idea that
      the State would not be able to afford it was not one. Indeed, that wise man
      William Beveridge had even mistakenly assumed, in the wartime White Paper on
      Social Security, that good health care would ultimately save money for the State,
      once an initial backlog of neglect had been made good, and that the cost of
      health insurance would then fall.

PMID- 8556286
TI  - Rationing in the NHS: the dance of the seven veils-in reverse.
AB  - The 1991 reforms of the National Health Service set up the expectation that
      rationing would in future be explicit instead of, as in the past, implicit. This
      has not happened. Research carried out at the University of Bath shows that very
      few health authorities are rationing by exclusion on the Oregon model. Instead,
      both central Government and health authorities are continuing to diffuse
      responsibility among the medical profession. This paper analyses the reasons why.
      Rationing by delay and dilution are more significant-as well as less visible-than
      rationing by exclusion. And it is the medical profession which controls the flow
      of patients through waiting lists and the way in which resources are used during
      treatment. Similarly, it is in the self-interest of both central Government and
      health authorities that their resource decisions should continue to be disguised
      behind the veils of clinical discretion. Despite pressures for greater
      transparency, Britain's opaque form of rationing may therefore survive.

PMID- 8556287
TI  - Choices in health care: a contribution from The Netherlands.
AB  - In this paper it will be argued that choices in health care are necessary,
      desirable and just. An important choice that each society has to make, is: what
      basic services should be available to everybody independently of an individual's
      purchasing power? The Dutch Government Committee on Choices in Health Care
      advised the use of four criteria: basic care must be necessary, effective,
      efficient and cannot be left to the individual's responsibility. Because
      important decisions with respect to the second criterion-the effectiveness of
      care-are made by physicians in the consulting room or at the operating table,
      physicians do have a primary responsibility in making the right choices.

PMID- 8556288
TI  - Sweden: no easy choices.
AB  - This paper describes some characteristic aspects of the Swedish health care model
      which can explain why choices and prioritizing have been difficult to discuss
      officially until very recently. Health care is an important symbol and
      cornerstone of the welfare society and it is therefore difficult to admit and
      formulate the concept of limits regarding this part of society. Parallel to a
      considerable decrease in the health care sector's fraction of GDP during the last
      10 years, where real cuts have been more and more visible, a public discussion on
      choices has emerged. A parliamentary committee of politicians and experts has
      addressed the issue and published a final report in the spring of 1995. It
      proposes an 'ethical platform' as a base for addressing the issue and describes
      guidelines for prioritizing on a political-administrative level and clinical
      level.

PMID- 8556289
TI  - Core services and the New Zealand health reforms.
AB  - The last 5 years have seen dramatic changes in health care provision in New
      Zealand. Amidst considerable controversy, the 14 Area Health Boards were
      abolished in July 1993. The State now funds 4 Regional Health Authorities (still
      on the basis of a weighted population formula) from Vote Health (the health
      sector's share of public expenditure). The role of the National Advisory
      Committee on Core Health and Disability Support Services and other bodies in
      determining the annual policy and service obligations faced by the 4 Regional
      Health Authorities is discussed.

PMID- 8556290
TI  - On the Oregon trail.
AB  - On the eve of the 21st century, governments around the world are struggling to
      resolve the dual problems of health care cost and access. My own experience in
      addressing these issues as they manifest themselves in the US, and particularly
      in the state of Oregon, convinces me that successful health care reform, anywhere
      in the world, must sooner or later grapple with two questions: what are we buying
      with our health care dollars, and how do these expenditures relate to health?

PMID- 8556291
TI  - Synthesis: what can we learn from international experience?
AB  - International experience shows that rationing can occur through exclusions or
      through the use of guidelines. Oregon has chosen to ration by excluding certain
      services in order to move towards universal population coverage. New Zealand has
      avoided exclusions and has chosen to ration through the use of guidelines. The
      Netherlands is pursuing both approaches. The experience of these and other
      countries demonstrates that rationing is inherently difficult. Choices in health
      care can be informed by techniques drawn from economics and other disciplines but
      these techniques need to be used as part of debate and discussion in the process
      of arriving at decisions. Experts and the public can contribute to this process
      and strenuous efforts need to be made to ensure participation by a representative
      cross-section of the population. At its root priority setting is a political
      process shaped by beliefs and values. Increased transparency in decision making
      should promote greater accountability and increased public awareness of the
      nature of rationing.

PMID- 8556292
TI  - The ethics of rationing.
AB  - Rationing can occur at three levels of health care choice: the individual, the
      institutional and the social, with each level posing its own ethical problems.
      The institutional level is the focus of this paper. The principle of
      effectiveness may seem attractive, since it promises to ease the institutional
      dilemmas of rationing, but it is not straightforward to implement in the face of
      uncertainty. Greater efficiency also promises much, but concepts of benefit are
      contested and improving contractual performance has complications. Fairness can
      be a powerful criterion, but there are contested cases, for example age, where
      its meaning is unclear. Democratic responsiveness, for all its difficulties, is
      important to maintain in whatever process of rationing is chosen and this can be
      done by adopting some procedural devices.

PMID- 8556293
TI  - The doctor's dilemma.
AB  - The close relationship between expenditure on health care and the countless
      individual judgements made by doctors for their patients means that any
      discussion about rationing must involve the process of clinical decision-making.
      Increasingly, doctors are being drawn into rationing by two powerful forces.
      Firstly, through the corporate responsibilities of those working within a managed
      health care system in which organisational objectives and budgetary constraints
      are agreed and specified in a much more explicit way than ever before. Secondly,
      by the professionally-led movement towards more clinically effective practice.
      These, in combination, are leading towards a fundamental review of the nature and
      ethical basis of clinical practice in which the duty of doctors to individual
      patients must be balanced against the wider considerations.

PMID- 8556294
TI  - Help or hindrance? The role of economics in rationing health care.
AB  - The economic evaluation of alternative diagnostic and therapeutic interventions
      is not merely a help to the processes by which decision makers allocate scarce
      economic resources, it is an essential ingredient into those rationing processes.
      Clinicians and other decision makers who advocate the use of effectiveness data
      alone to determine who will be treated and who will be left in pain and
      discomfort may perpetuate the inefficient use of resources. Rationing, or
      resource allocation, in health care must be informed by knowledge of the costs
      and consequences (effects) or alternative interventions. To ignore the economic
      element in clinical choices, generates inefficiency, and therefore unethical
      practice. The great advantage of the economic approach to rationing is that it
      requires an explicit framework which identifies the costs and benefits of
      alternative actions in all domains of human action. The combination of
      explicitness and precision inherent in good economic evaluation can only help in
      the difficult task of producing further health benefits for patients from the
      limited resources of the NHS.

PMID- 8556295
TI  - Involving the public: practical and ethical issues.
AB  - There has been little theoretical or methodological debate about health care
      rationing. This paper discusses the technical, ethical and political issues
      surrounding health services priorities and rationing debates in the context of a
      survey that the authors carried out in the former City and Hackney Health
      District, which asked the public, and doctors, to prioritise health services. In
      particular, the issue of the implementation of findings from consultation
      exercises is raised.

PMID- 8556296
TI  - Rationing health care: the political perspective.
AB  - The politics of rationing are messy and treacherous. As long as rationing
      remained implicit, politicians were shielded from the impact of decisions about
      who to treat and who not to treat. Explicit rationing changes all this by making
      the process of reaching choices more visible. However, implicit rationing may
      actually be a better way of dealing with difficult and complex issues. There is,
      nevertheless, scope for improving the process and making it more open and
      accountable. While efforts to terminate ineffective treatments are welcome and
      overdue, they are not a substitute for rationing. Finally, while politicians are
      being called upon to set national priorities and guidelines for rationing care,
      there is resistance to doing so when the decisions are so context specific and
      can only be made effectively at a micro level.

PMID- 8556297
TI  - A policy agenda for health care rationing.
AB  - In any system of third party payment for health care, such care will be rationed.
      A clear policy agenda will be focused upon three questions: Who should ration?
      What mechanisms should exist for making and implementing rationing decisions?
      What are the criteria by which rationing should occur?

PMID- 8556298
TI  - Information for public choice.
AB  - The kind of information the public will need in order to take part in the
      rationing debate is examined. The public are interested in the debate both as
      taxpayers and as patients and they can have an input in a number of different
      ways. Their involvement at the level of general discussions about values and
      service priorities is problematic, because some of the methods used do not allow
      participants to ask questions or work through the implications of the information
      they have access to. The mechanisms for ensuring their involvement in planning
      service strategies are better known and the information requirements are clear.
      When patients are given more say in decisions about their treatment and care,
      they may choose different options to those favoured by health professionals, but
      more work still needs to be done on developing and presenting complex medical
      information and helping patients to make decisions.

PMID- 8556299
TI  - Contracting and choice.

PMID- 8556300
TI  - Clinical practice guidelines--do they enhance value for money in health care?
AB  - Since the rationing of scarce resources requires a targeting of those resources
      to obtain best value for money, it is important to have mechanisms for assuring
      effective health care. Clinical practice guidelines offer an opportunity for
      introducing evidence based health care into local practice and for influencing
      the commissioning of effective health care. The opportunities for guidelines to
      be influential are currently curtailed by developmental problems which have only
      recently been overcome. These problems and some of their solutions are discussed
      in a UK context, while using evidence from the considerable experience on
      guideline development in North America. In particular, the main attributes of
      guidelines are identified, the strengths and weaknesses of current guidelines,
      and their impact on patient care are considered. Overall, guidelines appear to
      have the potential for making a positive contribution to health care rationing
      through the better direction of resources and by limiting inappropriate variation
      in clinical practice.

PMID- 8556301
TI  - Can we do better?
AB  - In the introductory chapter, I claimed that rationing is a fact of life in the
      NHS, and that the rationing dilemma is worsening over time, primarily because
      what medicine can offer becomes vastly more sophisticated and in aggregate more
      expensive. What is implied in Nye Bevan's intent that every citizen should
      receive 'the best that medical skill can provide' is very different now from what
      it was in 1946 when the NHS Act was passed. And the going will be ever harder in
      the years ahead, since medical possibilities, offering genuine benefit for some,
      will continue to increase faster than national wealth.

PMID- 8556302
TI  - CRASH syndrome: clinical spectrum of corpus callosum hypoplasia, retardation,
      adducted thumbs, spastic paraparesis and hydrocephalus due to mutations in one
      single gene, L1.
AB  - L1 is a neuronal cell adhesion molecule with important functions in the
      development of the nervous system. The gene encoding L1 is located near the
      telomere of the long arm of the X chromosome in Xq28. We review here the evidence
      that several X-linked mental retardation syndromes including X-linked
      hydrocephalus (HSAS), MASA syndrome, X-linked complicated spastic paraparesis
      (SP1) and X-linked corpus callosum agenesis (ACC) are all due to mutations in the
      L1 gene. The inter- and intrafamilial variability in families with an L1 mutation
      is very wide, and patients with HSAS, MASA, SP1 and ACC can be present within the
      same family. Therefore, we propose here to refer to this clinical syndrome with
      the acronym CRASH, for Corpus callosum hypoplasia, Retardation, Adducted thumbs,
      Spastic paraplegia and Hydrocephalus.

PMID- 8556303
TI  - Frequent occurrence of the CFTR intron 8 (TG)n 5T allele in men with congenital
      bilateral absence of the vas deferens.
AB  - Isolated congenital bilateral absence of the vas deferens (CBAVD) is an autosomal
      recessive disorder which has recently been shown to be associated with cystic
      fibrosis (CF) mutations. As part of an effort to understanding the genetic basis
      of this disorder, we have analysed the entire coding sequence and all the
      intron/exon boundaries of the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene from 45 azoospermic individuals with this phenotype. We were able to
      detect a CFTR gene defect in 86% of chromosomes from these subjects. In addition
      to identifying 9 novel CFTR gene mutations, we found that a surprisingly high
      proportion (84%) of men with CBAVD who are heterozygous for a CF mutation carry
      the intron 8 polypyrimidine 5T CFTR allele on one chromosome. We hypothesise that
      this tight and significant (p < 10(-6)) linkage reflects the very mild impact of
      this mutation on CFTR gene expression. Although genetic heterogeneity cannot be
      excluded, CBAVD patients in whom no CFTR mutation has been detected are likely to
      harbour additional unidentified mild mutations. These observations have
      implications for the genetic counselling of CBAVD patients and CF families, and
      couples undergoing in vitro fertilisation procedures.

PMID- 8556304
TI  - Characterization of phenylketonuria alleles in the Italian population.
AB  - In order to identify the molecular basis of phenylketonuria (PKU) in Italy, we
      screened the entire coding sequence of the phenylalanine hydroxylase gene in 20
      Italian PKU patients, whose origins are scattered throughout Italy. The frequency
      of each identified mutation and of 5 other European mutations was determined
      within a panel of 92 Italian PKU patients. This approach allowed us to identify
      20 different PKU mutations and characterize 64% of the Italian PKU chromosomes.
      Eleven mutations (IVS10nt546, L48S, R158Q, R261Q, P281L, R261X, R252W, delta T55,
      IVS7nt1, IVS12nt1, Y414C) represent 55.4% of the Italian PKU alleles, the most
      common mutations being IVS10nt546 (12.4%) and L48S (9%). All the other mutations
      are very rare. These data confirm the great heterogeneity expected from previous
      RFLP haplotype studies. Genotype/phenotype correlation allowed for assessment of
      the clinical impact of the 20 identified mutations.

PMID- 8556305
TI  - Evidence of linkage between susceptibility to multiple sclerosis and HLA-class II
      loci in Italian multiplex families.
AB  - To verify whether multiallelic polymorphisms belonging to HLA class II genes are
      linked to multiple sclerosis (MS) in the Italian population, we studied 28
      multiplex MS families originating from different areas of Italy. Allelic
      characterization was carried out by analysis of RFLPs and oligonucleotide typing.
      Evidence supporting the existence of linkage between MS susceptibility and the
      HLA class II loci DRB1, DQA1 and DQB1 was provided using two non-parametric
      tests, affected sib-pair analysis, and affected-pedigree-member (APM) analysis.
      The APM analysis also suggested the existence of genetic heterogeneity for the
      HLA class II loci and MS susceptibility in our series. Linkage disequilibrium
      between MS susceptibility and the haplotype DRB1*1501,DQA1*0102,DQB1*0602 was
      demonstrated by applying the transmission linkage disequilibrium test to our
      families. Finally, lod score analysis suggests that in our Italian families, MS
      susceptibility is conferred by HLA class II alleles according to a low-penetrance
      autosomal recessive mode of inheritance.

PMID- 8556306
TI  - The genetic background of craniosynostosis syndromes.
AB  - Craniosynostosis syndromes are developmental disorders that cause an abnormal
      shape of the skull due to the premature fusion of cranial sutures. Enormous
      progress has been made recently in understanding the genetic background of these
      disorders and a classification of syndromes on a genetic basis is beginning to
      emerge. Members of at least three gene families that play an important role in
      vertebrate development are associated with different craniosynostosis syndromes.
      Here we review the genetic aspects of this fast-moving field.

PMID- 8556307
TI  - No evidence for segregation distortion of cystic fibrosis alleles among sibs of
      cystic fibrosis patients. European Working Group on Cystic Fibrosis Genetics.

PMID- 8556308
TI  - Exclusion mapping of classical late infantile neuronal ceroid lipofuscinosis
      (Jansky-Bielschowsky disease, CLN2)

PMID- 8556309
TI  - Endotoxaemia: where do we go from here?

PMID- 8556310
TI  - Sodium bicarbonate loading and the rules of racing.

PMID- 8556311
TI  - Artificial insemination in rabbits.
AB  - Artificial insemination (AI) in rabbits can be a useful aid to colony management.
      In this review, simple non-invasive techniques for semen collection and AI are
      described. Conception rates following AI can be equivalent to, or better than,
      those achieved by natural mating, with the added advantage that contact between
      animals is avoided. Ovulation can be induced reliably by the administration of a
      gonadotrophin releasing hormone analogue, buserelin, as an alternative to the use
      of a vasectomized buck or the injection of luteinizing hormone. The use of enzyme
      linked immunoassay kits for progesterone assay can assist colony management by
      rapidly identifying non-pregnant animals for re-insemination. Frozen-thawed sperm
      have been inseminated but careful attention to the cryopreservation technique is
      required to ensure good conception rates.

PMID- 8556312
TI  - Mediators and vascular effects in response to endotoxin.
AB  - Recent experimental findings indicate that endotoxin (i.e. lipopolysaccharide)
      interacts with specific membrane receptors localized to mononuclear phagocytic
      cells and neutrophils. Binding of endotoxin to these cells, together with
      endotoxin-induced activation of host vascular endothelium, initiates a series of
      signal transduction events that culminate in release of numerous biochemical
      mediators. The latter include cytokines, platelet-activating factor, thromboxane
      A2, prostaglandins, leukotrienes, nitric oxide, proteases, toxic O2 radicals, and
      vasoactive amines. These mediators orchestrate complex biological interactions
      and amplification signals that lead to cardiopulmonary dysfunction and multi
      organ failure within 4-6 h of experimental infusion of endotoxin into animals.
      The pathophysiological changes include decreased cardiac output, systemic
      hypotension, decreased blood flow and O2 delivery to tissues, intense pulmonary
      vasoconstriction and hypertension, bronchoconstriction, increased permeability,
      pulmonary oedema, ventilation-to-perfusion inequalities, hypoxaemia, and
      haemoconcentration. Metabolic alterations include increased blood lactate and
      pyruvate, metabolic acidosis, hyperkalaemia and hypoglycaemia. Potential
      therapeutic modalities for treatment of endotoxaemia/septic shock include
      specific antagonists directed against lipopolysaccharide, cytokine, and platelet
      activating factor receptors, monoclonal antibodies directed against cytokines and
      lipid A/core polysaccharides of endotoxin, antiproteases, and agents that block
      release of toxic O2 and arachidonic acid metabolites.

PMID- 8556313
TI  - Effects of sodium bicarbonate on fluid, electrolyte and acid-base balance in
      racehorses.
AB  - Sodium bicarbonate given by nasogastric tube has been used by some trainers as
      the key ingredient in a 'milkshake'. It has been suggested that such treatment
      given 3-5 h prior to racing may enhance a horse's racing performance by
      increasing the blood buffering capacity and enhancing lactate clearance from
      skeletal muscle, thereby delaying the onset of fatigue. Several experiments were
      conducted to examine the effects on fluid, electrolyte and acid-base values of
      0.5 g kg-1 dose of sodium bicarbonate, were examined. The effects of fasting, the
      simultaneous administration of glucose (0.5 g kg-1) or the withholding of water
      were also examined to determine whether they influenced the uptake and
      elimination of sodium bicarbonate. Six Thoroughbred horses were used, each
      wearing a urine and faecal collection harness. Prior to sodium bicarbonate
      administration, venous blood, urine and faecal samples were collected for 24 h to
      establish control values. After administration of sodium bicarbonate (0.5 g kg-1)
      in 2 l of water, samples were collected at various times for up to 46 h. There
      were significant increases in water consumption, from 0.5-2.3 l h-1 at 2 h post
      administration. Urine output increased by approximately three fold and did not
      return to control levels until 18 h post-administration. Urinary sodium
      concentration increased from 95 +/- 16 mmol l-1 (mean +/- SEM) to peak values of
      349 +/- 12 mmol l-1 at 12 h. In the 24 h after sodium bicarbonate administration,
      approximately 80% of the sodium intake (NaHCO3+feed) was excreted in the urine.
      There was no significant change in the total urinary potassium and chloride
      excretion. Faecal water content did not change following sodium bicarbonate
      administration, but there was an increase in faecal sodium content. The mean
      increase in venous blood bicarbonate concentration was 7.6 +/- 0.4 mmol l-1 after
      the 0.5 kg-1 dose. Water deprivation for 6 h after sodium bicarbonate
      administration, fasting or the co-administration of glucose did not affect the
      peak blood bicarbonate concentration or the time to peak concentration. However,
      the withholding of water did result in a faster rate of decrease in blood
      bicarbonate concentration when water was resupplied.

PMID- 8556314
TI  - The effect of bovine amniotic fluid on in vitro maturation of bovine oocytes.
AB  - Three experiments were carried out to investigate whether bovine amniotic fluid
      (BAF), when added as a protein supplement to the maturation medium, supports the
      in vitro maturation of pre-ovulatory bovine oocytes. In the first experiment, the
      medium was supplemented with three different concentrations of the BAF (10, 20
      and 50%, respectively). In the second experiment, the effects of a combination of
      two protein supplements BAF plus oestrus cow serum (BAF-OCS) and BAF plus bovine
      follicular fluid (BAF-BFF), on the in vitro oocyte maturation rates were
      evaluated. In the third experiment, the effects of three different protein
      supplements (BAF, OCS, and BFF) on the oocyte maturation percentages were
      compared. Maturation rates at the metaphase II stage, following supplementation
      with 20% BAF (77%) and 10% BAF (68%) were significantly higher (P < 0.001 and P <
      0.05, respectively) than those resulting from supplementation with 50% BAF (44%).
      Significant differences between the 10% BAF and 20% BAF treatments were not
      observed. Significant differences were, however, found between the BAF-OCS
      treatment (57%) and the BAF-BFF treatment (50%). The results obtained from the
      BAF and the OCS treatments (77 and 78%, respectively) were significantly higher
      (P < 0.05) than when BFF (60%) was used. It is concluded that supplementation of
      the in vitro maturation medium of pre-ovulatory bovine oocytes with BAF provides
      important levels of proteins and growth factors responsible for nuclear and
      cytoplasmic development.

PMID- 8556315
TI  - Characterization of the camel skin cell line Dubca.
AB  - A skin fibroblast cell culture was established from a 2-month-old dromedary
      foetus. The cells were transformed by infection with SV40 and cloned in soft
      agar. The established cell line is now designated Dubca cells (Dubai camel) and
      has been in permanent culture for 95 passages. The cell culture was examined
      morphologically, chromosome preparations made and DNA fingerprinting performed by
      hybridization with the oligonucleotide probe (GTG)5. SV40 large T antigen was
      detected by western blotting. The viral host range was determined by infection
      with viruses of different families. Camelpox virus (CaPV) bovine herpesvirus-1
      (BHV-1), vesicular stomatitis virus (VSV) and border disease virus (BDV) could be
      propagated in these cells.

PMID- 8556316
TI  - Identification of beta-adrenoceptor subtypes in bovine ovarian and myometrial
      cell membranes.
AB  - Beta-adrenoceptor (beta-AR) concentrations were measured in the ovary and in the
      myometrium of 36 adult Friesian cows using a radiometric assay. The beta-AR
      content in both tissues was determined using the highly specific antagonist (-)
      [3H]CGP 12177 and the amounts of beta-AR subtypes were discriminated in the
      presence of highly selective unlabelled ligands (CGP 20712A, ICI 118 551, CGP
      25827A). Scatchard analysis revealed a good linearity and Kd values suggested the
      existence of high affinity beta-adrenergic sites in the bovine genital tract.
      Total beta-AR concentrations in the ovary and in the myometrium were,
      respectively, 87 +/- 7 (SEM) and 240 +/- 27 fmol mg-1 of membrane protein. beta 2
      AR concentrations were significantly higher (P < 0.01) in the ovary (66 +/- 5)
      and the myometrium (180 +/- 29) than those of beta 1-AR (21 +/- 4 and 60 +/- 5,
      respectively). Significant differences (P < 0.05) were also to be found between
      high affinity state beta 2-AR and low affinity beta 2-AR concentrations, but
      their values correlated negatively in the two different tissues. Natural and
      synthetic agonists inhibited (-) [3H]CGP 12177 binding to beta-AR in the
      following order of potency: (-)isoproterenol > (+/-)clenbuterol > or = (
      )adrenaline >> >> (-)noradrenaline, whereas synthetic antagonists inhibited
      binding in the following order of potency: (-)propranolol >> (+/-)ICI 118 551 >>
      >> (+/-)CGP 20712A.

PMID- 8556317
TI  - The effect of xylazine epidural anaesthesia on blood gas and acid-base parameters
      in rams.
AB  - The blood gas and acid-base effects of epidural xylazine were studied in rams.
      Xylazine at a dose of 0.4 mg kg-1 led to a metabolic alkalosis with a significant
      increase of pH, plasma bicarbonate and base excess and respiratory depression.
      Epidural administration of xylazine provided prolonged and very effective
      analgesia during abdominal and hindlimb surgery in rams.

PMID- 8556318
TI  - Efficacy of strategic tilmicosin injection during an outbreak of respiratory
      disease in housed beef calves.

PMID- 8556319
TI  - Interaction of the beta-carboline harmaline with a GABA-benzodiazepine mechanism:
      an electrophysiological investigation on rat hippocampal slices.
AB  - An interaction of harmaline (HA), a beta-carboline, with benzodiazepine (Bzd)
      receptors, has been reported. HA perfusion induced a similar, although less
      potent, depressing effect as clonazepam (CLO) on the amplitude of the population
      spikes (PS) evoked by Schaffer collateral stimulation in the CA1 area of rat
      hippocampal slices. The suppressant effect of both CLO and HA on PS amplitude was
      reversed by simultaneous perfusion of the GABA antagonist picrotoxin. These
      results suggest that HA acts as a weak or partial agonist at Bzd receptors.

PMID- 8556320
TI  - Localization of putative dopamine D2-like receptors in the chick retina, using in
      situ hybridization and immunocytochemistry.
AB  - The actions of dopamine are mediated by 5 or more receptor subtypes, any of which
      may be coupled by G-proteins to adenylate cyclase (D1-family: stimulatory, D2
      family: inhibitory or no action). Postnatal ocular growth in the chick is a
      vision-dependent mechanism which involves D2-type receptors in either the retina
      or the retinal pigment epithelium (RPE). Although the dopaminergic amacrine cells
      are well described in the chick retina, only D2-receptors, but not D3- and D4
      receptors have been clearly localized, and the cells that express them have not
      been identified. In this study we showed that immunoreactive D2/3-receptor
      protein is localized to the photoreceptor inner segments, outer and inner
      plexiform layer and ganglion cell layer, as described previously (Wagner et al.,
      J. Comp. Neurol., 330 (1993) 1-13). D2-receptor mRNA was localized to cell bodies
      in all nuclear layers of the retina, whereas D4-receptor mRNA was restricted to
      the inner half of the retina. Immunoreactive D2-type receptors and their mRNA
      were observed also in the basal region of the RPE. Because of the widespread
      distribution of both D2- and D4-receptor mRNA in the chick retina and RPE and the
      lack of D3- and D4-receptor-specific antibodies, we were unable to identify which
      of the D2/3/4-receptor-bearing cells are involved in controlling ocular growth.

PMID- 8556321
TI  - Regional distribution of substance P binding sites in the brainstem of the human
      newborn.
AB  - The distribution of [3H]substance P ([3H]SP) binding sites in the brainstem of
      the human newborn was investigated in eleven cases (aged 1 h to 6 months) by in
      vitro quantitative receptor autoradiography. The binding of [3H]SP to newborn
      brainstem tissue was found to be saturable (for the eight cases examined, Kd and
      Bmax (M +/- S.E.M.) were 0.29 +/- 0.03 nM and 206 +/- 21 fmol/mg tissue,
      respectively). Competition studies showed unlabeled SP to be the most potent
      peptide for displacing [3H]SP binding from tissue sections. The desaturating
      effect of GTP on the specific binding of [3H]SP was also investigated, but was
      not found to be significant. Autoradiographic analysis showed that the neurokinin
      1 (NK-1)/SP binding sites were widely but unevenly distributed, and that they
      varied with age. The highest densities of (NK-1)/SP binding sites were observed
      in the locus coeruleus, olivaris inferior nuclei, raphe magnus and obscurus
      nuclei, while low to moderate densities were observed in other brainstem
      structures. These findings support the idea that SP is involved in cardiovascular
      regulation, and that it may interact with the catecholaminergic and/or
      serotonergic system.

PMID- 8556322
TI  - Distribution and seasonal variation of vasoactive intestinal (VIP)-like peptides
      in the nervous system of Helix pomatia.
AB  - The distribution of neuropeptides immunologically related to vasoactive
      intestinal peptide (VIP) and its precursor peptide preproVIP(111-122), as well as
      to other peptides of the VIP-family, was studied in the central and peripheral
      nervous and sensory system of the snail, Helix pomatia, by use of
      immunocytochemical methods. VIP and preproVIP immunoreactivity was present in
      somata and nerve fibres of all central ganglia. Hibernating snails contained on
      average a total of 670 VIP- and 763 preproVIP-immunoreactive neurons. The number
      of immunoreactive cells was substantially reduced by more than 50% in active
      snails during summer with an average of 289 VIP- and 356 preproVIP-immunoreactive
      neurons. Antiserum against VIP labelled nerve fibres next to blood vessels and
      smooth muscle cells, whereas preproVIP-like material was localized in nerve
      fibres and endocrine-like cells among dorsal body cells and in the connective
      tissue along fiber tracts. VIP-immunoreactive material was also found in
      accessory ganglia of small and large tentacles, ganglia of the lips, the sensory
      epithelium of the tentacles, free nerve endings between skin epithelial cells,
      neuronal cells in the retina and in the sensory epithelium of statocysts. The
      cell-specific distribution and the seasonal variation of VIP- and preproVIP-like
      peptides suggest that they may act as transmitters or modulators in the nervous
      and sensory system and may be involved in the physiological adaptation of central
      neurons during long-term resting periods of snails.

PMID- 8556323
TI  - Fas antigen expression in brains of patients with Alzheimer-type dementia.
AB  - Fas antigen (CD95) is a cell surface protein that mediates apoptosis. We have
      investigated the immunohistochemical localization of Fas antigen in postmortem
      brain tissue from control subjects, patients with Alzheimer-type dementia (ATD),
      and from a few patients with diffuse Lewy body disease, progressive supranuclear
      palsy and adrenoleukodystrophy. In all brains, including controls, vascular
      endothelial cells and residual blood plasma were weakly stained. In ATD brains,
      senile plaques and a small number of star-like cells were brains of patients with
      neurological diseases other than ATD. In double immunostaining for Fas and glial
      fibrillary acidic protein (GFAP), a small number of cells were positive for both
      antigens. The majority of Fas-positive astrocytes were, however, negative for
      GFAP. This implies the downregulation of GFAP production in these cells. Doubly
      labeled astrocytes were also found around senile plaques, suggesting that the Fas
      immunoreactivity in senile plaques was derived from astrocytic membranes. The
      results of this study indicate that Fas antigen is expressed by a subset of
      reactive astrocytes in degenerative neurological diseases. Such astrocytes may
      undergo the Fas-mediated apoptotic process.

PMID- 8556324
TI  - Lack of correlation between glutamate-induced depletion of ATP and neuronal death
      in primary cultures of cerebellum.
AB  - The aim of this work was to identify, using primary cultures of cerebellar
      neurons, the receptors involved in glutamate-induced depletion of ATP and to
      assess whether there is a correlation between glutamate-induced ATP depletion and
      neuronal death. Glutamate induced a rapid depletion of ATP (40% decrease at 5
      min). After 60 min incubation with 1 M glutamate ATP content decreased by 60-70%.
      Similar effects were induced by glutamate, NMDA and kainate while quisqualate,
      AMPA or trans-ACPD did not affect significantly ATP content. The EC50 were
      approximately 6, 25 and 30 microM for glutamate, NMDA and kainate, respectively.
      DNQX and AP-5, competitive antagonists of kainate and NMDA receptors,
      respectively, prevented in a dose-dependent manner the glutamate-induced
      depletion of ATP. These results indicate that glutamate-induced depletion of ATP
      is mediated by activation of kainate and NMDA receptors. Glutamate-induced
      neuronal death was prevented by MK-801, calphostin C, H7, carnitine,
      nitroarginine and W7. However, only MK-801 and W7 prevented glutamate-induced
      depletion of ATP, while calphostin C, H7, carnitine and nitroarginine did not.
      This indicates that there is not a direct correlation between ATP depletion and
      neuronal death.

PMID- 8556325
TI  - Chronic effects of single intrastriatal injections of 6-hydroxydopamine or 1
      methyl-4-phenylpyridinium studied by microdialysis in freely moving rats.
AB  - Extracellular dopamine (DA) and its main cerebral metabolites,
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were measured by
      bilateral striatal microdialysis in rats at different times (2, 7, 15 and 60
      days) after unilateral administration into the right striatum of 1-methyl-4
      phenylpyridinium ion (MPP+) or 6-hydroxydopamine (6-OHDA). In both cases the
      decrease in extracellular dopamine did not exceed 40% of control values. The
      response of DOPAC and HVA depended on the treatment: MPP+ caused a marked acute
      decrease in the dopamine metabolites but allowed a progressive recovery that was
      very evident after 60 days; 6-OHDA caused a progressive decrease in the dopamine
      metabolites throughout the two months of the study. Tyrosine hydroxylase
      immunostaining revealed severe neuronal loss in substantia nigra two months after
      striatal administration of 6-OHDA, whereas no significant neuronal loss was found
      at the same time after MPP+ administration. A bilateral challenge infusion of
      MPP+ through the microdialysis probe was used to assess the dopaminergic capacity
      of both striata: at all the times studied there was a sharp depletion of DA on
      the non-lesioned side; both MPP(+)- and 6-OHDA-treated striata were unresponsive
      after a short time (2 days); after 2 months the response in MPP(+)-lesioned rats
      was similar on both sides, whereas 6-OHDA-lesioned striata were still
      unresponsive to MPP+. In rats, then, the effects of MPP+ could be partly reversed
      whereas the effects of 6-OHDA were not. These results suggest that neurotoxins
      causing striatal dopamine loss may act through different mechanisms, which could
      be significant for the etiopathogenic development of Parkinson's disease.

PMID- 8556326
TI  - Circadian changes in long-term potentiation of rat suprachiasmatic field
      potentials elicited by optic nerve stimulation in vitro.
AB  - Optic nerve stimulation caused a postsynaptic field potential in the rat
      suprachiasmatic nucleus (SCN) of hypothalamic slices. In the present experiment,
      we demonstrated whether tetanic stimulation of optic nerve can produce a long
      term potentiation (LTP) in the SCN postsynaptic field potential. The amplitude of
      SCN field potential was higher in the subjective day animals than that in the
      subjective night animals. Tetanic stimulation of optic nerve (100 Hz, 1 s) at
      subjective daytime (projected zeitgeber time: ZT 0-8) produced a LTP in this
      field potential, although the onset of LTP was slow. When tetanic stimulation was
      applied at ZT4, the percent increase of amplitude was 116.6% immediately after,
      159.8% 30 min after and 215.4% 120 min after tetanic stimulation, whereas tetanic
      stimulation of optic nerve at subjective night-time caused a weak LTP in the SCN.
      Although tetanic stimulation of Schaffer collaterals induced a LTP formation in
      the CA1 region of rat hippocampal slices, there were no obvious circadian changes
      in this LTP formation. The present results demonstrated that excitatory influence
      on the SCN caused a synaptic plasticity such as LTP. Although the physiological
      meaning of this LTP is uncertain at present, LTP may be related to adaptation
      mechanism to photic stimulation.

PMID- 8556327
TI  - Effects of bicuculline and baclofen on paired-pulse depression in the dentate
      gyrus of epileptic patients.
AB  - Paired-pulse field responses were recorded from the granule cell layer of the
      dentate gyrus in brain slices from temporal lobe epileptic patients. Paired-pulse
      depression (PPD) was examined using perforant path stimulation of low to moderate
      intensity at an inter-stimulus interval (ISI) of 20 ms. The paired-pulse ratio
      (PS2/PS1) was expressed as the population spike amplitude of the second response
      (PS2) relative to that of the first response (PS1). Representative tissue
      response from each patient biopsy were divided into two groups that were
      significantly different based on the magnitude of the highest paired-pulse ratio
      recorded for each biopsy specimen: the strong paired-pulse depression group
      (PS2/PS1 = 0.12 +/- 0.03; n = 15) and the weak paired-pulse depression group
      (PS2/PS1 = 0.68 +/- 0.06; n = 13). Paired-pulse ratios from the strong PPD group
      were relatively independent of stimulus intensity, whereas, PPD was dependent on
      stimulus intensity in the weak PPD group; i.e., PPD was greatest at the lowest
      intensity and reached a plateau at higher intensities. Bicuculline (20 microM)
      and low concentrations of baclofen (0.1-0.2 microM) reduced paired-pulse
      depression in the strong PPD group, but did not significantly change the paired
      pulse ratio in the weak PPD group. Paired-pulse facilitation was observed in some
      cases after inhibition was blocked pharmacologically. The number of population
      spikes was increased in the presence of bicuculline but was unchanged by
      baclofen. In the strong PPD group, baclofen significantly altered the EPSP
      population spike (E-S) relationship by increasing the slope of the relationship
      for the second response, without having an effect on the slope of the first
      response. Baclofen had no effect on the E-S relationship of either response in
      the weak PPD group. The data are consistent with (1) less inhibition in the weak
      PPD group compared to the strong PPD group, (2) reduction of feedback inhibition
      in the strong PPD group by bicuculline and by low concentrations of baclofen, and
      (3) the occurrence of paired-pulse facilitation when inhibition was
      pharmacologically reduced in the dentate gyrus of temporal lobe epileptic
      patients. The results are also consistent with the presence of GABAB receptors on
      human inhibitory interneurons that, when activated by baclofen, result in
      disinhibition of granule cells through feedback circuits. Although inhibition may
      be compromised in some epileptic human biopsy specimens, the presence of strong
      inhibition in other patients' biopsy material suggest the re-evaluation of the
      role of inhibition in epilepsy.

PMID- 8556328
TI  - Axonal degeneration promotes abnormal accumulation of amyloid beta-protein in
      ascending gracile tract of gracile axonal dystrophy (GAD) mouse.
AB  - The GAD mouse is a spontaneous neurological mutant with axonal dystrophy in the
      gracile tract of the medulla oblongata and spinal cord. The immunoreactivity of
      amyloid precursor protein (APP-IR) and amyloid beta-protein (A beta P-IR) was
      examined in the gracile tract and the dorsal root ganglia of normal and GAD mice.
      The mice were studied at 4, 9, 18, and 32 weeks of age. These periods correspond
      clinically to the initial, progressive, critical, and terminal stages of the
      disease, respectively. The APP-IR in both axons and glial cells was already
      accentuated to a higher level as early as 4 weeks of age in the gracile nucleus
      of GAD mouse. Similarly there was increase in APP-IR of GAD mouse in the dorsal
      root ganglia. Almost all of the primary neurons in the dorsal root ganglia at the
      lumbar cord level of GAD mouse revealed stronger APP-IR than those of normal
      mouse throughout all stages. The cells showing immunoreactivity for amyloid beta
      protein became positive in axons and glial cells in the gracile nucleus by
      approximately the 9th week, and followed by an increase of A beta P-IR in order
      of the cervical, thoracic and lumbar spinal cords. These results suggest that the
      initial feature in GAD mouse is an accumulation of amyloid precursor protein
      induced by axonal dystrophy which then leads to a deposition of amyloid beta
      protein within the cytoplasm of both axons and glial cells in the gracile tract.

PMID- 8556329
TI  - Suppression of presynaptic calcium influx by metabotropic glutamate receptor
      agonists in neonatal rat hippocampus.
AB  - Mechanisms of presynaptic inhibition by metabotropic glutamate receptor (mGluR)
      agonists were investigated in neonatal rat hippocampal CA1 region using the
      optical recording technique recently developed. Following selective loading of
      presynaptic terminals with a fluorescent Ca2+ indicator dye rhod-2 AM, changes in
      Ca2+ signals and the corresponding field excitatory postsynaptic potentials
      (EPSPs) induced by single electrical stimuli to the Schaffer collateral
      commissural (SCC) pathway were recorded simultaneously. Application of a mGluR
      agonist, 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 100 microM)
      or (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD; 100
      microM), reversibly reduced both the field EPSP and the presynaptic Ca2+
      transient, and the quantitative relationship between them was quite similar to
      that observed during application of Cd2+, a non-selective Ca2+ channel blocker,
      or in a Ca(2+)-free solution. Application of 4-aminopyridine (4-AP; 1 mM), a
      blocker of certain subtypes of voltage-dependent K+ channels, significantly
      inhibited the 1S,3R-ACPD effect. Application of DCG-IV, a novel mGluR2/mGluR3
      selective agonist, suppressed field EPSPs only slightly even at a high dose (3
      microM). These results suggest that activation of presynaptic mGluR different
      from mGluR2/mGluR3 suppresses the action potential-triggered Ca2+ influx,
      probably via 4-AP-sensitive mechanisms, and thereby reduces glutamate release in
      neonatal rat hippocampal CA1 region.

PMID- 8556330
TI  - Curve-shift analysis of self-stimulation in food-restricted rats: relationship
      between daily meal, plasma corticosterone and reward sensitization.
AB  - Chronic food restriction lowers the threshold for lateral hypothalamic electrical
      self-stimulation (LHSS). This effect has previously been interpreted to reflect a
      sensitization of reward. In the present study a curve-shift method was used to
      explicitly differentiate effects of food restriction on brain stimulation
      rewarding efficacy and performance. Food restriction consistently shifted rate
      frequency curves to the left, lowering the M-50 and Theta-0 parameters of
      rewarding efficacy. Asymptotic rates of reinforcement and slopes of rate
      frequency functions were unaffected, confirming that food restriction does not
      facilitate LHSS by enhancing performance. In this and previous studies, LHSS in
      food-restricted rats was measured in the period immediately preceding the daily
      meal when hunger (i.e., period since last meal) and plasma corticosterone are at
      peak levels. In the light of evidence that corticosterone may regulate
      sensitivity of the mesolimbic dopamine pathway and account for the sensitizing
      effect of stress on psychomotor effects of opiates and stimulants, LHSS and
      corticosterone were measured in the immediate pre-and post-meal periods. While
      all food-restricted rats displayed elevated corticosterone levels in the pre-meal
      period and generally displayed a decline to control levels in the post-meal
      period, the sensitization of reward was not reversed in the post-meal period.
      These results indicate that chronic food restriction produces a sensitization of
      reward that does not depend upon the acute state of hunger that precedes the
      daily meal and does not vary with dynamic changes in plasma corticosterone level.

PMID- 8556331
TI  - The extent and mechanism of the loss of function caused by strongly hypotonic
      solutions in rat hippocampal slices.
AB  - To investigate whether prolonged severe swelling would cause irreversible injury
      to neurons, we exposed hippocampal tissue slices to hypotonic solutions (142
      mosmol/kg) and followed the recovery of evoked responses for 5 h. Orthodromically
      evoked responses increased during hypotonia, except during recurrent waves of
      spreading depression (SD). After restoring normal osmotic pressure (pi o), evoked
      potentials became profoundly depressed. Following 30 min exposure, nearly maximal
      orthodromic responses recovered completely but responses to submaximal stimuli
      remained depressed, indicating elevated threshold. Following 60 min exposure,
      orthodromic transmission remained depressed. In slices from young animals,
      antidromic population spikes recovered completely, but in slices from older rats
      they remained partly depressed. Withdrawing calcium and raising magnesium
      concentration before and during hypotonic exposure resulted in modest but
      significant improvement of the recovery of synaptically transmitted responses,
      but made no difference for antidromic responses. With [Ca2+]o reduced and [Mg2+]o
      elevated, electrographic seizures replaced the episodes of SD during low pi o
      treatment. We conclude that even 60 min of severe hypotonic swelling did not kill
      CA1 pyramidal cells in tissue from young rats, but in its aftermath synaptic
      transmission was disrupted. Uptake of calcium may have played a minor role in the
      impairment of synaptic transmission. We propose hypothetically that post
      hypotonic shrinkage of dendrites disrupted the integrity of excitatory synapses.

PMID- 8556332
TI  - Hypotonic exposure enhances synaptic transmission and triggers spreading
      depression in rat hippocampal tissue slices.
AB  - Low extracellular osmotic pressure (pi o) is known to enhance CNS responsiveness
      and the chance of seizures, but the mechanism of the hyperexcitability is not
      clear. We recorded evoked potentials in st. radiatum and st. pyramidale of CA1.
      Tissue electrical resistance (Ro) was determined from the voltage drop (VRo)
      evoked by constant current pulses. Lowering of pi o by reducing [NaCl] caused a
      concentration-dependent increase of amplitude and duration of extracellular
      excitatory postsynaptic potentials (fEPSPs). fEPSPs increased much more than did
      VRo, but antidromic population spikes increased in proportion to VRo. fEPSP
      increased also in isosmotic low NaCl (fructose or mannitol substituted)
      solutions, but not as much as in low pi o. In moderately hypotonic solutions
      orthodromic population spikes increased as expected from the augmented fEPSP, but
      in strong hypotonia input-output curves shifted to the left and single stimuli
      evoked multiple population spikes, indicating lowering of threshold of
      postsynaptic neurons. Blocking N-methyl-D-aspartate (NMDA) receptors did not
      diminish the enhancement of fEPSP amplitude. Spreading depression (SD) erupted in
      most slices in very low pi o, but not in isoosmotic low [NaCl] solutions. We
      conclude that the hypotonic enhancement of EPSPs depends, in part, on the
      lowering of [Na+]o and/or of [Cl-]o, and it may be augmented by dendritic
      swelling favoring electrotonic spread of EPSPs from dendrites to somata, and
      buildup of transmitter concentration due to swelling of perisynaptic glia. SD can
      be initiated by cell swelling, but the depolarization associated with SD is
      probably not caused by the opening of stretch-gated ion channels.

PMID- 8556333
TI  - Characteristics of a fast transient outward current in guinea pig trigeminal
      motoneurons.
AB  - A fast transient voltage dependent outward current (TOC) in trigeminal
      motoneurons (TMNs) was studied in guinea pig brainstem slices by use of sharp
      electrodes in combination with single electrode voltage clamp techniques. In
      solutions containing TTX, low Ca2+/Mn2+ and 20 mM TEA this current activated
      around -55 to -60 mV from holding potentials negative to resting potential,
      obtained its peak amplitude within 5 ms and decayed as a single exponential with
      a time constant of 6-8 ms. Half maximal values for inactivation and activation
      were -72 and -37 mV, respectively. Bath application of 5 mM 4-AP suppressed this
      current by approximately 90% and eliminated the early depolarizing transient
      membrane rectification observed in response to a constant depolarizing current
      pulse, prolonged the action potential duration, and reduced the threshold voltage
      and delay to onset of the action potential. It is suggested that this current
      resembles the typical A-current observed in many CNS neurons and, as a result of
      its voltage and time dependent properties, could contribute to control of
      motoneuronal discharge and timing of burst onset during rhythmical jaw movements.
      Therefore, any cellular models of masticatory activity should include the
      properties of this current.

PMID- 8556334
TI  - Histamine synthesis inhibition reduces light-induced phase shifts of circadian
      rhythms.
AB  - Circadian rhythms are generated by the hypothalamic suprachiasmatic nuclei, a
      site of dense histaminergic innervation. Histamine can phase shift circadian
      rhythms in a manner similar to light. In this experiment, we administered alpha
      fluoromethylhistidine (FMH), an inhibitor of histamine synthesis, prior to a
      light pulse in hamsters housed under constant darkness. Photic phase shifts in
      wheel-running rhythms were significantly attenuated by FMH pretreatment. These
      results suggest that histamine may modulate photic input to the circadian clock.

PMID- 8556335
TI  - Interaction of cationic liposomes with cells of electrically active neuronal
      networks in culture.
AB  - Incubation of rhodamine-labeled cationic liposomes with mature murine spinal
      cultures results in strong fluorescence that is evenly distributed on somata and
      neurites of neurons in 7 different cultures. Staining of the glial carpet is
      minimal. Rhodamine-labeled dextran, encapsulated in liposomes, also stains
      neurons. Electron microscope data show external attachment and intact
      internalization of liposomes. Spontaneous electrical bursting activity is altered
      but not lost after incubation.

PMID- 8556336
TI  - Circadian rhythm of spontaneous neuronal activity in the suprachiasmatic nucleus
      of old hamster in vitro.
AB  - The effects of aging on neuronal activity in the suprachiasmatic nucleus (SCN)
      were examined in hamsters kept under light-dark (LD) or constant light (LL)
      conditions. The free-running period in wheel-running rhythm of 24-month-old
      hamsters (24.2 +/- 0.04) was shorter than that of the 2-month-old hamsters (24.4
      +/- 0.057). There was a significant difference in the mean firing rates of SCN
      neuron activity between old and young hamsters during subjective day (6.58 +/-
      0.36 spikes/s in young and 5.63 +/- 0.24 in old hamsters), but not during
      subjective night (4.33 +/- 0.47 in young and 4.05 +/- 0.39 in old). Similar to LL
      condition, the firing activity during zeitgeber time 3-11 (4.33 +/- 0.27) in old
      hamsters kept under LD condition, was significantly lower than that of young
      hamsters (6.22 +/- 0.32). These results suggest that deterioration of SCN
      neuronal activity in old hamsters assessed as reduction of daytime activity may
      reflect changes in the interaction between SCN clocks and the overt behaviors
      and/or pacemaking properties of SCN cells.

PMID- 8556337
TI  - Age-dependent and region-specific differences in the distribution of trace
      elements in 7 brain regions of Long-Evans Cinnamon (LEC) rats with hereditary
      abnormal copper metabolism.
AB  - Cu, Mn, Mo, Rb and Zn concentrations of 7 brain regions in LEC rats were
      determined before (4 and 10 weeks old) and after (20 weeks old) the onset of
      jaundice. Cu in the LEC rat brain was less concentrated in all regions at 4 weeks
      of age and in synaptosomal fractions at 10 weeks but, conversely, more
      concentrated in 3 regions at 20 weeks than in control rats. Furthermore, Mo and
      Rb in 6 regions at 10 weeks of age and Mn at 20 weeks were more concentrated in
      the LEC rat brain than in control rats. These results showed that abnormal
      distributions of trace elements exist in the LEC rat brain before the onset of
      jaundice.

PMID- 8556338
TI  - Verapamil treatment attenuates immunoreactive GFAP at cerebral cortical lesion
      site.
AB  - Cerebral cortical lesions were produced using a stereotactic injection system in
      Sprague-Dawley rats randomly assigned to three groups: (1) needle lesioned and
      uninjected (Lesioned), (2) needle lesion and simultaneous local injection of 50
      or 100 microliters 0.9% saline (L/Saline), and (3) needle lesion and simultaneous
      local injection of 50 or 100 microliters Verapamil-HCl (VHCL) (2.5 mg/ml (5 mM)
      Abbott Labs, Chicago, IL), a passive, L-type calcium channel blocker (L/VHCL).
      The lesioning induced expression of glial fibrillary acidic protein (GFAP), a
      type of intermediate filament protein expressed in reactive astrocytes, at the
      lesion site. There was a reduction in GFAP-like immunoreactivity (GFAP-IR) in the
      L/VHCL group versus the Lesioned and the L/Saline groups. There was a five-fold
      increase of GFAP-IR at 24 h post lesion in the L/Saline group, but no
      statistically significant increase seen in the Lesioned or L/VHCL groups at
      either volume. Pretreatment of the anti-GFAP with VHCL did not impair the antigen
      labeling. To determine whether differences in pHs, or volume could account for
      these findings, a second experiment was performed using pH-matched saline or VHCL
      in 10 microliters volume injected into contralateral hemispheres at the time of
      lesioning. There was an 80% reduction in GFAP-IR in the L/VHCL group at 72 h
      compared with the L/Saline group. These data suggest that VHCL may suppress the
      early increase of GFAP-IR in response to cortical lesion and that reducing
      transmembrane calcium flux through L-type calcium channels may be the mechanism
      involved.

PMID- 8556339
TI  - Effects of lidocaine injections into the lateral parabrachial nucleus on
      dipsogenic and pressor responses to central angiotensin II in rats.
AB  - This study investigated the effects of bilateral injections of the local
      anesthetic, lidocaine, into the lateral parabrachial nucleus (LPBN) on the
      dipsogenic and pressor responses induced by intracerebroventricular (i.c.v.)
      injection of angiotensin II (ANG II). Centrally injected ANG II (50 ng/1
      microliters) induced water intake (10.2 +/- 0.8 ml/h) and pressor responses (22
      +/- 1 mmHg). Prior bilateral injection of 10% lidocaine (200 nl) into the LPBN
      increased the water intake (14.2 +/- 1.4 ml/h), but did not change the pressor
      response (17 +/- 1 mmHg) to i.c.v. ANG II. Lidocaine alone injected into the LPBN
      also induced a pressor response (23 +/- 3 mmHg). These results showing that
      bilateral LPBN injection of lidocaine increase water intake induced by i.c.v. ANG
      II are consistent with electrolytic and neurotoxic lesion studies and suggest
      that the LPBN is associated with inhibitory mechanisms controlling water intake
      induced by ANG II. These results also provide evidence that it is feasible to
      reversibly anesthetize this brain area to facilitate fluid-related ingestive
      behavior.

PMID- 8556340
TI  - Involvement of bulbospinal pathways in the antinociceptive effect of clomipramine
      in the rat.
AB  - The involvement of bulbospinal pathways in the antinociceptive effect of
      clomipramine in experimental pain was studied. The antinociceptive effect of the
      antidepressant (0.5 mg/kg), intravenously injected, was evaluated after a
      unilateral lesion of the dorsolateral funiculus. The results showed that this
      effect was suppressed only in the hindpaw ipsilateral to the dorsolateral
      funiculus lesion, and suggest that the antinociceptive effect of antidepressants
      needs intact descending inhibitory bulbospinal pathways.

PMID- 8556341
TI  - Nitric oxide synthase in the hypothalamic suprachiasmatic nucleus of rat:
      evidence from histochemistry, immunohistochemistry and western blot; and
      colocalization with VIP.
AB  - Nitric oxide (NO) is a neuroactive substance of high potency. Physiological
      results revealed the involvement of NO in circadian regulation of rats. Since
      neuronal structures containing NO-synthase (NOS) were previously not found in the
      circadian oscillator, the hypothalamic suprachiasmatic nucleus (SCN), in this
      species but are present in the hamster, we investigated the distribution of NO
      producing structures in the rat SCN by Western blot analysis,
      immunohistochemistry of NOS, and by histochemistry (NADPH-diaphorase (NADPH-d)
      activity of NOS). Western blot analysis of SCN homogenates from rat (and, for
      comparison, hamster) showed a NOS-like immunoreactive (-LI) protein band of
      apparent molecular mass of 150 kDa, consistent with the neuronal NOS molecule. In
      the rat SCN, perikarya exhibiting NADPH-d staining of NOS-LI with a complete
      overlapping of both were found. Double-immunofluorescence experiments revealed
      that NOS cells are a subgroup of the neuronal SCN population that is
      characterized by immunoreactivity to vasoactive intestinal polypeptide. These
      data provide evidence for the existence of neuronal nitric oxide synthase in the
      rat SCN and may explain the involvement of NO in the mediation of photic
      information.

PMID- 8556342
TI  - Light microscopic evidence of serotoninergic projections to olivocochlear neurons
      in the bush baby (Otolemur garnettii).
AB  - Double-label techniques were used to concomitantly label olivocochlear neurons
      and serotoninergic fibers in the bush baby (Otolemur garnettii) brainstem. Light
      microscopic examination (using a 100 x plan apochromatic oil-immersion objective)
      of the sections revealed that serotonin-positive varicosities (presumptive
      terminal endings) contacted somata and dendrites of neurons belonging to both the
      lateral and medial olivocochlear neurons near the superior olivary nuclei. These
      results provide direct evidence that the olivocochlear system (a specific
      auditory brainstem pathway) receives input from the serotoninergic system (a
      diffuse reticular brainstem network).

PMID- 8556343
TI  - Microinjection of morphine into the rat medullary dorsal horn produces a dose
      dependent increase in facial scratching.
AB  - It has been proposed that opioids act at the level of the medulla to produce
      facial pruritus. Supporting this hypothesis, microinjection of mu-opioid receptor
      agonists into the medullary dorsal horn (MDH; trigeminal subnucleus caudalis) of
      monkeys produces facial scratching behavior. The present study sought to
      establish a rodent model of opioid-induced facial pruritus. To this end, morphine
      (0.1, 0.3 or 1.0 micrograms/0.2 microliter) or saline (0.2 microliter) was
      unilaterally microinjected into the MDH of male Sprague-Dawley rats. Behavior for
      the 20 min preceding and the 80 min after this microinjection was videotaped.
      Morphine produced dose-dependent increases in facial scratching behavior
      ipsilateral to the microinjections with the peak effect at 30-40 min after
      microinjection. Facial scratching continued for the entire 80 min post
      microinjection test period. Morphine also produced a lesser degree of facial
      scratching contralateral to the microinjections. Increases in facial scratching
      ipsilateral to the microinjection of 0.3 microgram morphine into the MDH were
      attenuated by 0.4 mg/kg s.c. naloxone. These findings support the hypothesis that
      the MDH is a critical site of action of opioid agonists in producing facial
      pruritus.

PMID- 8556344
TI  - Effects of ethanol on respiratory activity in the neonatal rat brainstem-spinal
      cord preparation.
AB  - Ethanol (1-12 mM) added to the superfusion medium of the isolated brainstem
      spinal cords of newborn rats did not affect phrenic activity but significantly
      reduced hypoglossal activity by 54%, 67% and 55% at 3, 6 and 12 mM, respectively.
      Although the reasons for the suppression of hypoglossal activity remain unknown,
      this preparation may be a useful model for determining why cranial motoneurons
      are more vulnerable than phrenic motoneurons to various agents and, more
      generally, how ethanol impairs neural function.

PMID- 8556345
TI  - Role of lateral parabrachial nucleus in the inhibition of water intake produced
      by right atrial stretch.
AB  - Rats with either bilateral electrolytic or sham lesions of the ventrolateral
      portion of the lateral parabrachial nucleus (VLLPBN) were implanted with latex
      balloons that lay at the right superior vena cava/atrial junction (RSVC/AJ).
      Water intake in response to isoproterenol was measured both with and without
      inflation of the balloon. Water intake of the sham-lesioned rats was
      significantly depressed by balloon inflation during the first hour of the
      experiment. In contrast, water intake in the VLLPBN-lesioned rats was unaffected
      by balloon inflation. These results suggest that the VLLPBN is involved in the
      processing of afferent input from stretch-activated RSVC/AJ receptors.

PMID- 8556347
TI  - Projections from the 17/18 visual area transition zone to the ipsilateral visual
      field representation in the cat superior colliculus.
AB  - We demonstrate by retrograde tracing methods that the transition zone between
      visual cortical areas 17 and 18--where a representation of the ipsilateral visual
      field (IVF) has been described--projects to the IVF representation in the
      ipsilateral superior colliculus. The stratum griseum superficiale is the target
      of this retinotopically organized cortical projection to the rostral part of the
      superior colliculus.

PMID- 8556346
TI  - Intracerebroventricular interleukin-1 receptor antagonist blocks the enhancement
      of fear conditioning and interference with escape produced by inescapable shock.
AB  - Brain interleukin-1 (IL-1) plays a key role in mediating the neural, endocrine,
      and behavioral consequences of injury and infection. Recent evidence indicates
      that brain IL-1 may also be important in producing endocrine and neurochemical
      responses to stressors. The present experiment sought to determine whether
      intracerebroventricular (i.c.v.) administration of an interleukin-1 receptor
      antagonist (IL-1ra) would block behavioral effects of a stressor. I.c.v.
      application of hrIL-1ra before inescapable shock blocked the subsequent
      interference with escape learning and enhancement of fear conditioning normally
      produced by this treatment.

PMID- 8556348
TI  - A protective effect of lithium on rat behaviour altered by ibotenic acid lesions
      of the basal forebrain cholinergic system.
AB  - Lithium was tested on an animal model of a brain cholinergic excitotoxic lesion.
      Male Wistar rats received unilaterally 50 nmol ibotenic acid in the nucleus
      basalis magnocellularis. Some were treated intraperitoneally with LiCl from two
      days before to six days after lesioning. Such treated rats showed less deficits
      than untreated lesioned animals on passive avoidance, ambulatory behaviour and
      choline acetyltransferase activity in the lesioned cortex. Lithium protection
      against excitatory amino acid neurotoxicity is suggested.

PMID- 8556349
TI  - Correlated activity in the spinocerebellum is related to spinal timing
      generators.
AB  - Encoding of information by neuronal populations implies a correlation of neural
      activity across cells. Therefore recent evidence for correlated activity in
      different parts of the nervous system has been interpreted as a possible
      mechanism for functional coupling or coordinated information processing. We
      compared the activity in the mossy fiber projection, the dorsal spinocerebellar
      tract (DSCT) with the responses of Purkinje cells in the spinocerebellum for
      evidence of correlated activity. A principal component analysis of post-stimulus
      spike activity revealed temporal patterns of correlated Purkinje cell activity in
      all parts of the spinocerebellum evoked by rapid, small amplitude passive joint
      rotations in anesthetized cats. The same basic temporal patterns were induced in
      DSCT neurons by joint rotations and also by direct nerve stimulation, showing
      that the patterning resulted from centrally generated rather than peripheral
      timing. The evidence implies that spinal timing generators, activated by
      mechanical stimulation of the ipsilateral hindlimb, transmit temporally
      correlated activity to the cerebellum via spinocerebellar pathways resulting in a
      coherent modulation of activity in diverse areas of the cerebellar cortex thereby
      providing the basis for a functional coupling.

PMID- 8556350
TI  - [The phenomenon of hypoglycemia unawareness--definition, frequency, pathogenesis
      and clinical forms].
AB  - Failure to recognize autonomic warning symptoms or failure for them to occur
      before the development of neuroglycopenia is defined as hypoglycemia unawareness.
      Incidence of this phenomenon among patients with insulin-dependent diabetes
      mellitus is frequent. Using a standardized insulin infusion test it has been
      found that one out of four patients (26%) with insulin-dependent diabetes
      mellitus has present hypoglycemia unawareness. Various mechanisms and
      predisposing factors have been implicated in the pathogenesis of the phenomenon
      of hypoglycemia unawareness. This defect is probably at the central nervous
      system level and could be due to: 1. lack of appropriate recognition by the
      central nervous system of a decreasing glycemia (altered hypothalamic glucostat
      function or altered blood-brain glucose transport); 2. diminished release of
      neurotransmitters; 3. diminished target tissue responses on appropriate
      neurotransmitters secretion. Theory of pathogenesis of hypoglycemia unawareness
      must be able to explain and define its association with duration of diabetes,
      strict glycemic control, autonomic neuropathy and repetitive episodes of
      hypoglycemia. The present hypothesis of hypoglycemia unawareness is that the
      repetitive frequent hypoglycemia leads to generalized central nervous system
      adaptation by means of increased transport of glucose through the blood-brain
      barrier which results in diminished counterregulatory hormone responses and
      symptoms. A dangerous vicious circle develops whereby hypoglycemia induces
      unawareness, which in itself increases the risk for development of new
      hypoglycemia. This state is at least partially reversible. The presence of
      hypoglycemia unawareness should influence the physician's decision before using
      intensive insulin therapy regimen in diabetic patients. (Tab. 2, Fig. 1, Ref.
      39.)

PMID- 8556351
TI  - [Analysis of arrhythmias using Holter electrocardiographic monitoring in patients
      with ventricular preexcitation].
AB  - BACKGROUND: It is known that patients with preexcitation of ventricles (PE) have
      a predisposition to paroxysmal supraventricular tachyarrhythmias (PSVT). There is
      a relatively small amount of knowledge concerning the occurrence and clinical
      significance of other disturbances of the cardiac rhythm in these patients.
      OBJECTIVES: 1. To consider the possibility of utilization of Holter monitoring
      (HM) of electrocardiograms (ECG) in the detection of PSVT; 2. To find out the
      occurrence and evaluate the significance of other than paroxysmal tachycardias;
      3. By means of correlation of subjective complaints with objectively documented
      arrhythmias to consider the extent, to which the subjective complaints are
      determined by disturbances of cardiac rhythm. METHODS: 24-hour HM ECG was
      performed under clinical conditions in 50 patients, 23 male and 27 female
      patients at the average age of 35 +/- 13 (ranging 15-17) years, with manifestant
      PE on ECG. 21 (42%) patients with documented PSVT and/or atrial paroxysmal
      fibrillation (APF) constituted a group with Wolff-Parkinson-White (WPW) syndrome.
      29 (58%) patients without these arrhythmias were ranked among the group with WPW
      pattern. 22 (44%) patients had concomitant organic heart disease (OHD). Each long
      term electrocardiographic ECG recording was judged in order to specify the
      occurrence of individual types of arrhythmias and to perform their quantitative
      analysis per 24 hours. Subjective complaints presented by patients during HM were
      correlated with the objectively documented arrhythmias. RESULTS: Arrhythmias were
      recorded in HM in 35 (70%) of patients with PE. Supraventricular premature beats
      (SVPBs) occurred in 32 (64%) and ventricular premature beats (VPBs) in 15 (32%)
      patients with PE. When comparing the patients with PE and OHD with subjects with
      PE without OHD, no statistical differences in the occurrence of SVPBs and VPBs as
      well as in numbers per 24 hours were discovered. PSVT were recorded by HM only in
      2 patients, and AV reciprocating echoes in another patient with WPW syndrome.
      Short runs of atrial tachycardia occurred in 2 patients with WPW syndrome.

PMID- 8556352
TI  - [Serum levels of vitamins A, C and E in the population of Slovakia].
AB  - BACKGROUND: Significant forms of vitamin deficiencies are rare in Slovak
      Republic, however mild hypovitaminoses are still relatively frequent and they
      have negative consequences on the functional status. Vitamins A, C and E
      represent an important part of the antioxidant defense system acting against free
      radical damage. Imbalance between oxidative stress and antioxidant capacity which
      leads to free radical damage is considered to be an aetiological factor of
      ischaemic heart disease and cancer. OBJECTIVES: The study was focused on
      assessment of serum levels of vitamins A, C and E in the Slovak population older
      than 35 y and frequency of decreased levels. Relationship between high prevalence
      of chronic non-communicable diseases and high frequency of suboptimal levels of
      antioxidant vitamins is discussed. METHODS: Serum levels of vitamin A and E were
      assessed by the HPLC method, the levels of vitamin C by the colorimetric method.
      RESULTS: Mean levels of vitamin A were 1.85 mumol/l in both sexes (95% c.i. 1.75
      1.89 in males, 1.77-1.92 in females). Mean level of vitamin C was 31.36 mumol/l
      in males (95% c.i. 30.06-32.72), the value observed in females was significantly
      higher (43.05 mumol/l, 95% c.i. 41.75-44.40). Mean level of vitamin E observed in
      males (29.2 mumol/l, 95% c.i. 27.62-30.87) was only slightly, not significantly
      higher than in females (28.11 mumol/l, 95% c.i. 26.45-29.87). Decreased levels of
      vitamin E were observed only in a small proportion of the sample, however almost
      one third of males had decreased level of vitamin C and more than 20% had low
      level of vitamin A. We observed high prevalence of serum levels of vitamins A, C
      and E suboptimal from the aspect of risk of coronary heart disease and cancer
      (vitamin A: males 78%, females 75.5%, vitamin E: 41.9 and 49.6%, respectively,
      vitamin C: 61.8% and 41.1%). CONCLUSION: Results indicate that sizeable
      proportion of population has decreased serum levels of vitamins, males especially
      of vitamin C and females of vitamin A. According to serum levels of vitamin A, C
      and E high percentage of population can be ranked into the group with increased
      risk of CHD and cancer. (Tab. 6, Ref. 29.)

PMID- 8556353
TI  - [Laparoscopic peroperative cholangiography--indications and significance].
AB  - The authors have performed 35 peroperative laparoscopic cholangiographies by
      means of transcystic cannylation of the choledochus in 410 patients subdued to
      laparoscopic cholecystectomy. Choledocholelithiasis was found in 8 patients
      (22.85%). The authors advocate for the application of peroperative
      cholangiography in indicated cases since the method is simple, safe and
      sufficiently successful. (Tab. 5, Ref. 9.)

PMID- 8556354
TI  - [Visual evoked potentials after stimulation with motion--basic characteristics].
AB  - The study presents a methodical analysis and results of examinations of visual
      evoked potentials after stimulation by pattern reversion and motion in the visual
      field. The stimulus is generated on a PC monitor. In this manner selective
      stimulation of X and Y ganglionic cells is enabled by reversion, motion and their
      mutual combination. (Tab. 1, Fig. 2, Ref. 14.)

PMID- 8556355
TI  - [Diverticulosis of the small intestine].
AB  - Small bowel diverticulosis is a rare disease of gastrointestinal tract that
      occurs most frequently in older patients. Since this disease can be asymptomatic,
      for a long time, the diagnosis rarely is made in the preoperative period. In 40%
      of cases there are acute or chronic complications, most frequently diverticulitis
      either with or without perforation, bowel obstruction and massive haemorrhage
      clinically manifested as bleeding from the lower part of the gastrointestinal
      tract. Abdominal pain, pseudoobstructive and malabsorption syndrome, expressive
      weight loss, steatorrhea and anemia are common chronic complications. In these
      cases a surgical treatment is necessary. Resection of the affected part of the
      small bowel is usually performed with end-to-end anastomosis. The authors present
      4 cases with diverticulosis of the small bowel, two cases of which were
      manifested by diverticulitis and one of them was perforated. Pseudoobstructive
      syndrome, malabsorption and expressive weight loss were presented in other two
      cases. All four cases were dominated by severe abdominal pain. The surgical
      treatment was based upon radical resection of the small bowel with end-to-end
      anastomosis. (Fig. 4, Ref. 28.)

PMID- 8556356
TI  - [Prevention and treatment of lymphatic fistulas after arterial reconstruction in
      the lower extremity].
AB  - Lymphatic fistula is a complication of 2% of surgical vascular reconstruction in
      the groin especially in the critically ischaemic limb. We investigated the
      incidence of lymphatic fistula, its prevention and treatment in patients at the
      Department of Surgery of the Ruzinov Hospital in Bratislava during the period of
      5 years. 7 patients out of 162 (4.44%) had lymphatic fistula in the groin. The
      patients underwent 172 operation involving 209 groin incisions. Lymphatic fistula
      developed in 7 groin incisions--3.34%. Operations included 36 aortobifemoral
      bypass procedures, 2 unilateral bypass procedures, 76 femoropopliteal bypass
      procedures or profundoplastic surgeries, 48 embolectomies. The diagnosis was
      based upon the clinical findings of the characteristic persistent watery
      discharge in the groin after vascular operation. Conservative treatment was
      successful in all patients, the average duration of lymphatic fistula was 27.2
      days. Lymphatic fistula may be complicated in 25% of patients by wound infection
      but it shouldn't be regarded as the first degree of infection in vascular
      surgery. (Ref.12)

PMID- 8556357
TI  - [Antioxidant status in vegetarians living in Bratislava].

PMID- 8556358
TI  - The role of peroxisomes in intermediary metabolism.
AB  - The dominant position among oxidoreduction processes in peroxisomes is ascribed
      to catalase, a number of aerobic oxidases, and Cu,Zn-superoxide dismutase. The
      peroxidase reaction of catalase requires substrates for hydrogen donation, other
      than H2O2, e.g. alcohols, aldehydes, formic acid. The peroxisomes contain an
      alternative system of beta-oxidation of higher carboxylic acids which in some
      types of plant cells is functionally very closely associated with the glyoxylate
      cycle. Regarding the role of peroxisomes in the metabolism of carboxylic acids, a
      very important finding has taken place, namely that besides acyl-CoA synthetase
      which is specific for long chains, the peroxisomes contain still another enzyme
      which allows the synthesis of CoA esters of fatty acids with very long chains. It
      is assumed that the entry of acyl-CoA esters or fatty acids into the perxisomes
      is performed by means of pores in membranes or acyl-carnitine transferases.
      Peroxisomes oxidize a very wide scale of substrates and contain several types of
      acyl-CoA oxidases: palmitoyl-CoA oxidase, pristanoyl-CoA oxidase, trihydroxy
      coprostanoyl-CoA oxidase. The second and third reactions of peroxisomal beta
      oxidation are catalyzed by the so-called three-functional enzyme, the activities
      of which are identical to those of 2-enoyl-CoA hydratase, beta-hydroxyacyl-CoA
      dihydrogenase and enoyl-CoA isomerase. The peroxisomes sufficiently oxidize
      dicarboxylic acids with a higher number of carbons beginning with the adipic
      acid. The peroxisomal system of beta-oxidation is utilized in metabolism of
      prostaglandins, pristanic acid-being the product of phytanic acid alpha
      oxidation, and cholesterol. Several enzymatic activities needed for the synthesis
      of cholesterol partially take place in peroxisomes. The peroxisomes represent a
      decisive compartment for the initial phases of synthesis of plasmalogens. They
      contain the following enzymes: NAD(+)-glycerol-P-dehydrogenase, dihydroxyacetone
      3-P-acyl-transferase, alkyl-dihydroxyacetone-P synthetase and acyl/alkyl
      dihydroxyacetone-P reductase. The metabolism of amino acids takes place under the
      effect of peroxisomal enzymes--oxidase of diamino acids, D-aspartate oxidase,
      oxidase of L-pipecolic acid and alanine-glyoxylate aminotransferase. Only a few
      published sources consider it obvious that liver peroxisomes participate in
      degradation of spermine and spermidine. Polyamine oxidase oxidizes spermine
      resulting in the origin of spermidine and 3-aminopropionaldehyde, and spermidine
      is oxidized to putrescine and 3-aminopropionaldehyde. Peroxisomes in many
      phylogenetically lower animal species enable the break down of purine bases to
      urea and glyoxylic acid. In phylogenetically higher primates and in man, the
      activities of urate oxidase in peroxisomes are absent. (Fig. 14, Ref. 166).

PMID- 8556359
TI  - [Treatment of viral hepatitis].
AB  - Chronic forms of viral B,C and D hepatitis and fulminant hepatitis represent a
      serious healthcare problem. The study deals with the changes in the strategy in
      treating these diseases. During the chronic active hepatitis caused by the B
      hepatitis virus, the main aim of treatment is to cease multiplication of viruses,
      eliminate the clinical symptoms, prevent the development of cirrhosis, or the
      origin of hepatocellular carcinoma. The authors analyze the possibilities of the
      application of corticosteroids, viricidal drugs (vidarabin and interferons) and
      other medicaments (acyclovir, zidovudin, duramin, gancyclovir, chinacrin, and
      others) besides corticosteroids, interleukin 2 and tymozin from the group of
      immunomodulators were tested. The testing included the factor stimulating the
      colonies of granulocytes and myeloblasts and other substances. The therapy of
      acute protracted B hepatitis by means of interferon still requires controlled
      studies. Superinfection by D virus in chronic carriers of HBsAG causes chronic
      hepatitis which quickly leads to the development of cirrhosis. The therapy on
      basis of alpha interferon decreases the RNA virus D hepatitis serum level and
      leads to an improvement in the development of chronic hepatitis in half of the
      patients. Therapy of chronic C hepatitis on basis of corticosteroids is
      ineffective, and can be dangerous. Acyclovir is proved to be ineffective as well.
      The open study indicated certain positive results in application of interferon.
      The fulminant hepatitis can be defined as a development of encephalopathy and a
      decrease of the prothrombin time to less than 50% in the course of acute
      hepatitis. The break-point in the therapy of fulminant hepatitis took place in
      association with the performance of the transplantation of the liver.
      Impossibility to transplant the liver means that the effect of therapy of
      fulminant hepatitis is merely of supportive value. Majority of patients die due
      to neurologic complications, namely unmanageable oedema of the brain. But still,
      neither the antioedema therapy, e.g. on basis of manitol, as well as by means of
      corticosteroids, hemodialysis, hemofiltration, plasmapheresis and hemoperfusion,
      nor the treatment on basis of E1 prostaglandine improved the survival of
      patients. (Tab. 2, Ref. 82).

PMID- 8556360
TI  - [Laparostomy in the treatment of severe hemorrhagic-necrotic pancreatitis].
AB  - The authors present their experience with the therapy of severe necrotic
      pancreatitis which was applied in the period from 1986 to 1993. Alcoholic
      etiology was stated in 52.56% patients. The authors analyse in detail the cases
      treated with "open packing" laparostomy. They emphasise its advantages and
      advocate to its more frequent application. Laparostomy in the frame of complex
      therapy of acute pancreatitis can contribute to mortality reduction. The
      mortality in the group of patients yielded 17.75%. Complications and multiorgan
      failure with a high mortality rate and severe forms of necrotic pancreatitis
      still represent a sad component of abdominal surgery. (Tab. 6, Ref. 13).

PMID- 8556361
TI  - [Reasons for conversion in laparoscopic cholecystectomy].
AB  - Laparoscopic cholecystectomy (LCH) is a surgical method which is minimally
      invasive thus enjoying an increasing popularity among both patients among the
      patients surgeons. Conversion of laparoscopic cholecystectomy is comprehended as
      a retrieve to the classical surgical method based on laparotomy in any phase of
      operation. The study deals with reasons for conversion of the initial one hundred
      LCH which were performed by 7 surgeons at the Department of Surgery in Ruzinov
      Hospital in Bratislava during the period from 27.11.1992 to 31.3.1994. Out of one
      hundred cases, 5 LCH required conversion to open laparotomy--5%. The most
      frequent rate of conversion is from 3 to 8%. Reasons for conversion in our
      patients include. Impossibility to introduce safety the trocar with the video
      camera (1x), unclear anatomic situation (1x), bleeding from the cystic artery
      (1x), perforation of the gallbladder and subsequent leakage of bile and stones in
      to the peritoneal cavity (1x), technical failure (1x). We cannot comprehend the
      conversion of LCH as a failure of the operating surgeon. It insinuates that the
      surgeon is careful and responsible for his patient. It is a sign of his good
      surgical judgement.

PMID- 8556362
TI  - [The short bypass in the treatment of popliteal artery occlusion].
AB  - Authors present in case report a patient with occlusion of proximal section of
      popliteal artery which was resolved by the reconstructive vascular surgical
      procedure--short femoropopliteal bypass using autolognal saphenous vein as a
      graft. In discussion they deal with the problem of short bypass in traumatic
      injured lower extremities and also in atherosclerotic or other degenerative
      diseases of lower extremities arteries. On the account of particulars from
      literature they refer to the possibility of using various autolognal venous
      grafts and also artificial vascular protheses. They also deal with the adjuvant
      medical treatment from the point of view of prevention of a favourable closure of
      graft and its longterm patency. They presume that the short bypass is in
      indicated cases mainly in highly at risk patients fully justifiable.

PMID- 8556363
TI  - The treatment of children with acute megakaryoblastic leukemia who have Down
      syndrome.

PMID- 8556364
TI  - Perspectives on investigational chemotherapy and biologic therapy for childhood
      brain tumors.

PMID- 8556365
TI  - Glanzmann thrombasthenia in children from Argentina.
AB  - PURPOSE: Glanzmann thrombasthenia is a well-defined inherited disorder of
      platelet function characterized by a decrease or absence of functional platelet
      glycoprotein (GP) GPIIbIIIa. The diagnosis must be considered in patients
      presenting with mucocutaneous bleeding, purpura, a normal platelet count,
      abnormal platelet aggregation, and a prolonged bleeding time. In most of the
      patients, the presence of small amounts of either GPIIb or GPIIIa was detected in
      their platelets. These observations could provide a basis for determining the
      clinical and laboratory heterogeneity of the disease. PATIENTS AND METHODS: We
      studied 10 patients of seven unrelated families with the usual methods and an
      immunoalkaline phosphatase technique (APAAP) to analyze the biosynthesis of GP in
      megakaryocytes. RESULTS: The results allowed us to classify six patients as GT
      type I, three as type II, and one as a variant. CONCLUSION: The nature and
      severity of the bleeding manifestations, in our patients, were not predictible by
      the laboratory findings. These confirm the clinical and laboratory heterogeneity
      of the disease.

PMID- 8556366
TI  - The absence of ongoing immunoglobulin gene hypermutation suggests a distinct
      mechanism for c-myc mutation in endemic Burkitt's lymphoma.
AB  - PURPOSE: Burkitt's lymphoma is a malignancy of mature, immunoglobulin (Ig)
      bearing B cells characterized by translocation between c-myc and Ig gene loci. A
      role for the juxtaposed Ig genes in the mutation and deregulation of c-myc
      expression typical of endemic Burkitt's lymphoma (eBL) has been proposed, but
      never proven. Our objective was to determine whether Ig gene hypermutation is
      ongoing in eBL. METHODS: We isolated Ig heavy-chain sequences from K962 eBL tumor
      cells using reverse transcription and polymerase chain reaction (PCR)
      amplification. The PCR product was ligated into Bluescript II vectors. Multiple
      subclones were sequenced and the variable regions were compared for evidence of
      ongoing Ig hypermutation. RESULTS: Six total single base substitutions were
      observed within four of the nine subclones studied. Four substitutions resulted
      in amino acid changes and two were silent. There was no clustering of mutations
      in hypervariable regions, or a high incidence of amino acid replacement or link
      substitutions, all of which are characteristic of Ig hypermutation. The observed
      mutations occurred at a rate consistent with Taq polymerase error. CONCLUSIONS:
      Our data indicate that in the eBL tumor sample K962, the mechanism underlying c
      myc mutation is distinct from that which gives rise to Ig hypermutation.

PMID- 8556367
TI  - Child Health 2000: 2nd World Congress and Exposition. Vancouver, Canada, May 30
      June 3, 1995. Concurrent conferences on hematology--oncology: Challenges in
      childhood cancer and blood diseases.

PMID- 8556368
TI  - Newborn screening for sickle cell disease: 4 years of experience from
      California's newborn screening program.
AB  - PURPOSE: In this article we describe the success of a unique newborn screening
      program for sickle cell disease and other hemoglobinopathies. We will present and
      discuss 4 years of experience from the California Newborn Hemoglobinopathy
      Screening Program. METHODS: Several aspects that ensure the success of the
      program will be reviewed. These aspects include (a) the use of high-pressure
      liquid chromatography as the initial screening technique, (b) a confirmatory
      testing laboratory that incorporates DNA technology and innovative protein
      analysis using electrospray mass spectrometry, and (c) a complex follow-up
      strategy that employs regional nurses to track positive results and ensure timely
      enrollment of infants into treatment systems. RESULTS: Of these 2 million infants
      screened, 492 were diagnosed with some form of sickle cell disease; 290 (58.9%)
      were diagnosed with hemoglobin SS, 143 (29.0%) were diagnosed with hemoglobin SC,
      and 47 (9.5%) were diagnosed with S beta+thalassemia. CONCLUSION: The prevalence
      and ethnicity data presented here demonstrate the ineffectiveness of targeted
      screening and justify universal screening. Had targeted screening been performed
      in California during the past 4 years, 58 nonblack infants with sickle cell
      disease would have gone undiagnosed, and 6,921 nonblack infants with sickle cell
      trait would not have been identified.

PMID- 8556369
TI  - Ototoxicity in hemoglobinopathy patients chelated with desferrioxamine.
AB  - PURPOSE: Ototoxicity often limits the dose of desferrioxamine (DFO) tolerated by
      patients who are transfusion dependent. Current recommendations advise doses of <
      50 mg/kg/day after early reports noted higher rates of oxotoxicity with
      increasing doses. There have been no follow-up studies to determine the effect of
      this recommendation on oxotoxicity and iron overload. METHODS: We followed 28
      patients who were chronically chelated with serial audiograms over a 5-year
      period. Patients with and without oxotoxicity were compared with respect to age,
      disease, DFO dose, peak DFO dose, length of DFO therapy, ferritin, and
      therapeutic index. RESULTS: Eight of the 28 patients (29%) had an abnormal
      audiogram during threshold testing. Two patients had two separate episodes with
      hearing deficit. Nine of the 10 episodes were high-frequency losses, with seven
      being moderate and three mild. All deficits were rapidly reversible with DFO dose
      reduction. No significant differences were found between the affected and
      unaffected groups with respect to age, DFO dose or duration, ferritin, or
      therapeutic index. Numbers of affected patients were small, but patients with SCD
      differed from patients with thalassemia in that they developed ototoxicity
      earlier and with lower doses of DFO and lower therapeutic indexes. CONCLUSIONS:
      Despite DFO doses usually felt to be low risk for ototoxicity, we found a high
      rate of ototoxicity in our patients who we've chronically chelated. No variables
      were identified that reliably predicted ototoxicity. We stress the need for
      regular audiological exams and feel no dose of DFO is "safe" from the development
      of ototoxicity.

PMID- 8556370
TI  - Erythrocytapheresis can reduce iron overload and prevent the need for chelation
      therapy in chronically transfused pediatric patients.
AB  - PURPOSE: This research was undertaken to determine the advantages, complications,
      costs, and efficacy of erythrocytapheresis in young pediatric patients who
      receive chronic erythrocyte transfusion therapy. PATIENTS AND METHODS: We
      retrospectively analyzed data for 10 children who received erythrocytapheresis
      for an average of 16 months. Erythrocytapheresis was compared to simple
      transfusion therapy with respect to annual blood unit exposure, occurrence of
      alloimmunization, and costs. Serum ferritin levels were compared before and after
      the period of erythrocytapheresis. RESULTS: Erythrocytapheresis was well
      tolerated, even in children as young as 5 years or as small as 20 kg. It required
      a greater annual unit exposure than simple transfusions, but did not increase
      alloimmunization. Ferritin levels decreased significantly in children receiving
      concurrent deferoxamine, and decreased or stabilized in those not on chelation
      therapy. Children started on erythrocytapheresis soon after stroke have not
      developed iron overload. Although the costs of erythrocytapheresis exceed that of
      simple transfusion, the substantial costs of deferoxamine therapy should be
      considered; one child on erythrocytapheresis has been able to discontinue
      chelation therapy following normalization of his ferritin level. CONCLUSION:
      Erythrocytapheresis is a safe and effective method for young patients receiving
      chronic erythrocyte transfusions. Erythrocytapheresis can reduce total iron
      burden and may obviate the need for expensive chelation therapy.

PMID- 8556371
TI  - Detection of bone lesions in Langerhans cell histiocytosis: complementary roles
      of scintigraphy and conventional radiography.
AB  - PURPOSE: This research was undertaken to determine the relative sensitivity of
      scintigraphic and radiographic bone survey examinations in detecting bone lesions
      in various regions of the skeleton in patients with a histopathologic diagnosis
      of Langerhans cell histiocytosis (LCH). PATIENTS AND METHODS: Radionuclide
      skeletal scintigraphy (RNSS) and x-ray skeletal surveys (XRSS) of 42 children
      with a histopathologic diagnosis of LCH were evaluated retrospectively. RESULTS:
      Of the 191 lesions detected in 42 patients, 36 (19%) were missed on RNSS and 55
      (29%) were missed on XRSS. Most of the missed lesions on RNSS were in the skull
      (26 of 36). XRSS also missed 13 skull lesions seen on RNSS. Most of the lesions
      missed on XRSS were in the ribs (20 of 30 rib lesions), whereas RNSS identified
      29 of them. XRSS also missed 13 of 38 lesions in the spine and pelvis, while RNSS
      demonstrated all of them. Both modalities showed comparable sensitivity in the
      extremities. CONCLUSION: RNSS has a greater value in detecting sites of bone
      involvement with LCH than reported previously. RNSS is more sensitive than XRSS
      in detecting histiocytic lesions in the ribs, spine and pelvis and less sensitive
      in identifying lesions in the skull.

PMID- 8556372
TI  - Erythroblastic and/or megakaryoblastic leukemia in Down syndrome: treatment with
      low-dose arabinosyl cytosine.
AB  - PURPOSE: We report here the clinical response to low-dose arabinosyl cytosine
      (Ara-C) in seven children with Down syndrome (DS) and acute leukemia in which
      blast cells express markers of erythroid and/or megakaryoblastic lineages.
      Following an initial course of treatment with Ara-C, complete remission was
      obtained in all seven patients. Maintenance therapy with Ara-C was continued
      during complete remission. Four patients subsequently relapsed; the three others
      are disease-free. Based on these data, we suggest that when conventional therapy
      is contraindicated by associated malformations, low-dose Ara-C can be used for
      treating DS patients with erythroblastic or megakaryoblastic leukemia. The aim of
      this study was to assess the efficacy of low-dose Ara-C in treating
      megakaryoblastic and/or erythroblastic leukemia associated with DS. PATIENTS AND
      METHODS: Seven patients with DS presented with leukemia in which blast cells
      displayed early markers of the erythroblastic and/or megakaryoblastic lineage.
      Low-dose subcutaneous Ara-C (10 mg/m2 two times per day) was given for 21 days as
      induction therapy, followed by a 5-10-day course each month for 2 years as a
      maintenance treatment. RESULTS: Low-dose Ara-C treatment resulted in complete
      remission in all seven patients and in long-term disease-free survival in three
      patients. CONCLUSION: In cases in which conventional chemotherapy is
      contraindicated, low-dose Ara-C should be considered as a therapeutic alternative
      for treatment of DS-associated erythroblastic or megakaryocytic leukemia.

PMID- 8556373
TI  - Fractionated high-dose cyclophosphamide for advanced pediatric solid tumors.
AB  - PURPOSE: The objective of this study was to determine the tolerance and
      toxicities of high-dose cyclophosphamide (CPA) at 7 g/m2 given in four fractions
      over 8 h in children with advanced solid tumors. PATIENTS AND METHODS: Twenty
      children aged 1 1/2-19 years (median, 12 years) received 24 courses of high-dose
      CPA at 7 g/m2 for the treatment of advanced malignant solid tumor. CPA was given
      in four 1-h infusions of 1.75 g/m2 each, with 1 h of rest between each dose.
      MESNA was used as a uroprotective agent and was continued for 24 h after the
      final dose of CPA. With only one exception, all patients were discharged at the
      end of MESNA infusion and received granulocyte colony-stimulating factor,
      prophylactic ciprofloxacin, and co-trimoxazole. RESULTS: Severe but transient
      myelosuppression was observed. The median time to neutrophil and platelet
      recovery was 17 and 19 days, respectively. Fever developed after 13 of the 24
      courses, and hospitalization was required. Extramedullary toxicities were mild.
      No patient showed cardiomyopathy or hemorrhagic cystitis. Forty-six percent of
      the courses were managed entirely on an outpatient basis. Objective tumor
      response was seen in five patients. CONCLUSIONS: CPA at 7 g/m2 is well tolerated
      by children with advanced malignancies and should be considered in earlier phases
      of antineoplastic therapy.

PMID- 8556374
TI  - Bone marrow transplantation in pediatric patients with severe aplastic anemia:
      cyclophosphamide and anti-thymocyte globulin conditioning followed by recombinant
      human granulocyte-macrophage colony stimulating factor.
AB  - PURPOSE: Graft rejection remains a serious problem in patients transplanted for
      severe aplastic anemia. Although additional immunosuppression with irradiation
      may decrease graft failure, significant sequelae may ensue. We evaluated a
      nonirradiation containing conditioning regimen for children with severe aplastic
      anemia with matched sibling donors utilizing cyclophosphamide and anti-thymocyte
      globulin (ATG). To accelerate myeloid recovery, GM-CSF was used posttransplant.
      PATIENTS AND METHODS: Twelve patients, with a median age of 3 years underwent BMT
      from HLA identical sibling (n = 11) or syngeneic (n = 1) donors. Conditioning was
      cyclophosphamide 50 mg/kg x 4 days and anti-thymocyte globulin 30 mg/kg x 3 days.
      GM-CSF was administered at 10 micrograms/kg until a neutrophil count of 1,000 was
      achieved. Cyclosporine alone was used for graft-versus-host disease prophylaxis.
      RESULTS: All patients achieved durable engraftment at follow-up of 5-51 + months,
      with the exception of the identical twin. Median time to neutrophil counts >
      200/microliters, 500/microliters, and 1,000/microliters were 12, 13, and 15 days,
      respectively. Acute GVHD of less than or equal to grade II occurred in four
      patients; one patient had grade III. This has resolved in all but one.
      CONCLUSION: The nonradiation conditioning regimen of cyclophosphamide/ATG appears
      to achieve durable engraftment in transfused children with matched sibling
      donors. GM-CSF may accelerate myeloid recovery without exacerbating GVHD, but its
      contribution to allogeneic transplant required further study.

PMID- 8556375
TI  - Late echocardiographic findings following childhood chemotherapy with normal
      serial cardiac monitoring.
AB  - PURPOSE: Late development of myocardial dysfunction years following successful
      treatment of childhood malignancy with anthracyclines is well documented. There
      have been few studies of late cardiac performance in children in whom serial
      monitoring during treatment suggested normal cardiac performance, and those
      studies that do exist rely on the results of extensive evaluation. It was our
      purpose to determine whether findings consistent with known late cardiac changes
      could be discovered in these patients by echocardiographic monitoring similar to
      that routinely performed during treatment. PATIENTS AND METHODS: A total 28
      consecutive asymptomatic patients who had completed anthracycline therapy at
      least 3 years previously, had been free of malignant disease since the completion
      of therapy, and who had had normal serial echocardiographic studies during and at
      completion of treatment were restudied by echocardiography. Of these 28, 12 had
      undergone mediastinal radiation as part of their acute treatment. RESULTS: Four
      patients (14%) of the study group were found to have abnormally low values for
      left ventricular shortening and ejection fractions. All four had also received
      mediastinal radiation. The remaining 24 patients, while having values for
      shortening fraction within the normal range, had, as a group, experienced a
      significant decrease in echocardiographic left ventricular shortening since
      completion of treatment. In these patients, left ventricular wall thickness had
      not increased commensurate with growth in body size and left ventricular cavity
      dimension. CONCLUSIONS: The known incidence of late asymptomatic cardiac
      dysfunction is confirmed despite the presence of persistently normal
      echocardiographic monitoring studies during and at completion of anthracycline
      treatment. Additionally, as a population, these patients show impaired myocardial
      growth over time, placing them at risk for future myocardial failure. Normal
      echocardiographic monitoring studies during antineoplastic treatment in children
      may not necessarily predict that patients will be free of the development of late
      cardiac dysfunction. Routine serial echocardiographic monitoring can, however, be
      helpful in the long-term management of these patients.

PMID- 8556376
TI  - Hodgkin disease in children: reduced tailored chemotherapy for stage I-II
      disease.
AB  - PURPOSE: Between January 1982 and January 1994, 46 children with stage I-II
      Hodgkin disease were treated with a tailored regimen to maintain a high cure rate
      while reducing toxicity. PATIENTS AND METHODS: Forty-six previously untreated
      children with stage I-II Hodgkin disease received four to six courses of
      cyclophosphamide, oncovin, procarbazine, and prednisone (COPP) alternating with
      doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), tailored according
      to clinical response. Staging was based on various imaging modalities and gallium
      scan, but surgical staging was not performed. Radiotherapy was given only to
      bulky mediastinal disease. RESULTS: The median age at diagnosis was 13 years
      (range 4-18) and only 4 of 46 children had B symptoms. The majority (31 of 46)
      had stage II disease; 10 had bulky mediastinal disease. Nodular sclerosis
      histology predominated (32 of 46). Gallium scan was positive in 66% of the
      patients who were evaluated. Forty-three patients (93%) achieved complete
      remission after planned therapy. Thirty-six patients (78%) received chemotherapy
      alone, and 10 (22%) received combined-modality treatment. Fifteen children (33%)
      completed treatment with only four courses of COPP/ABVD. Overall freedom from
      relapse was 87% and overall survival was 98% with a median follow-up of 5 1/2
      years. Long-term treatment-related morbidity was found mainly in patients
      receiving radiotherapy. CONCLUSION: Comprehensive clinical staging combined with
      tailored COPP/ABVD therapy according to response results in excellent disease
      control and may reduce toxicity.

PMID- 8556377
TI  - Complications and effectiveness of gastrostomy feedings in pediatric cancer
      patients.
AB  - PURPOSE: The objective of this study was to assess the complications and efficacy
      of gastrostomy (GT) feedings in pediatric cancer patients. PATIENTS AND METHODS:
      We reviewed the medical records of 33 pediatric cancer patients who received
      enteral nutrition via a GT. RESULTS: Median age was 9.4 years (range, 1-19.8
      years), and 28 of the 33 patients had solid tumors. Seventeen patients had a
      significant weight loss (median, 8.5%) and therapy-related weight loss was
      anticipated in 16 patients. The GT device was placed an average of 5.5 months
      after diagnosis. Twenty-five patients were fed via a tube and eight via a button
      device. The tube was placed surgically in 21 cases (including all eight button
      types) and endoscopically in 12. Nutritional support lasted a median of 9.5
      months. One or more complications occurred in 30 patients and were categorized as
      (a) insertion site reactions (inflammation, 23; infection/colonization, 14;
      exuberant granulation tissue, 6); (b) mechanical problems (leaking, 3;
      obstruction, 2; breakage, 1; accidental dislodgement, 2); (c) insertion site
      bleeding, 8; and (d) feeding intolerance, 12. Only one insertion site cellulitis
      progressed to a systemic infection. All eight patients with a button GT
      experienced insertion site complications, with local infection occurring
      significantly more often in patients with the button than in those with the tube
      GT. There were no significant associations between insertion technique and type
      of complication. Twenty-seven patients (82%) achieved or maintained ideal body
      weight with this intervention. CONCLUSIONS: GT feeding was associated with minor
      complications, but permitted effective nutritional support for pediatric cancer
      patients.

PMID- 8556378
TI  - Hypermagnesiuria and hypercalciuria in childhood leukemia: an effect of amikacin
      therapy.
AB  - PURPOSE: The purpose of this study is to assess the effects of amikacin on renal
      proximal tubular function, and on magnesium (Mg) and calcium (Ca) status in
      children treated for acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS:
      Eighteen children (11 male/7 female, ages 2-18 years) receiving antileukemic
      therapy (Dana Farber Cancer Institute protocols 87-001 or 91-001) and admitted
      for febrile neutropenia to The Children's Hospital at Chedoke-McMaster, Hamilton,
      Ontario were recruited into this descriptive prospective study. Each child was
      treated with amikacin (7.5 mg/kg/12 h x 10-14 days) for one or more courses.
      RESULTS: No patient demonstrated elevations in amikacin trough levels. beta 2
      Microglobulinuria, glucosuria, proteinuria, and hyperphosphaturia were absent.
      Children (50% presenting with hypomagnesemia (< 0.77 mmol/L) had a significant
      rise in mean urinary Mg:creatinine (0.46 +/- 0.27 versus 0.82 +/- 0.38 mmol, mean
      +/- SD, p < 0.05) in response to amikacin therapy and the mean Ca:creatinine
      ratio increased by 95% after 10-14 days of amikacin treatment. Serum Mg and Ca
      did not change notably after treatment, irrespective of initial Mg status.
      CONCLUSIONS: Aminoglycoside therapy in children with ALL is not associated with
      overt nephrotoxicity. A transient renal leak of Mg and Ca does occur. Screening
      of ALL children for mild hypomagnesemia may help to identify those most at risk
      of disruption of renal conservation of Mg and possibly Ca.

PMID- 8556379
TI  - Opportunistic osteomyelitis in the jaws of children on immunosuppressive
      chemotherapy.
AB  - PURPOSE: Four children with an osteomyelitic process in the jaw bones while on
      cytotoxic chemotherapy were treated by radical surgery and antimicrobial
      chemotherapy. PATIENTS AND METHODS: Symptoms (local swelling and pain in the jaw,
      necrotic gingivitis, and spontaneous loss of teeth) appeared 3 weeks, 4 weeks,
      and 8 months after diagnosis of leukemia, and 8 days posttransplant in a patient
      with severe aplastic anemia. Three had the process in the mandible and one in the
      maxilla. Specific diagnoses of Aspergillus flavus, Saccharomyces cerevisiae, and
      Actinomyces species were obtained histologically from surgical samples. Treatment
      was radical surgery to remove all infected and necrotic tissue: removal of a
      substantial part of the mandible and loss of seven to eight permanent teeth in
      those with mandibular lesions. Actinomycosis was treated with penicillin for 2
      years. The patients with fungal lesions received amphotericin B for 2, 5, and 6
      months, with adjuvant itraconazole, fluconazole, or 5-fluorocytosine for 9-12
      months. Anti-cancer chemotherapy was continued. RESULTS: All the bony lesions
      healed. The patient with acute myeloid leukemia died in relapse 1 year
      postdiagnosis; her aspergillus osteomyelitis had been inactive for 8 months. The
      other three patients are alive and well 1.9, 2.1, and 1.9 years after termination
      of antimicrobial therapy. CONCLUSIONS: We emphasize the necessity of specific
      diagnosis from appropriate surgical samples and conclude that in patients
      undergoing chemotherapy bony lesions caused by opportunistic microorganisms may
      be curable with aggressive surgery and prolonged medication.

PMID- 8556380
TI  - Interaction between cyclosporine and danazol in a pediatric patient.

PMID- 8556381
TI  - Myelodysplastic syndrome in a child with Rothmund-Thomson syndrome: a case
      report.

PMID- 8556382
TI  - Recurrent human parvovirus B19-induced anemia: initial manifestation of humoral
      immunodeficiency.

PMID- 8556383
TI  - Transient erythroblastopenia in a child with Kawasaki syndrome: probable
      parvovirus B19 infection?

PMID- 8556384
TI  - Aristotle, nursing and health care ethics.
AB  - Even a brief consideration of the nature of nursing will indicate that an ethical
      dimension underlies much, if not all, of nursing practice. It is therefore
      important that students and practitioners are facilitated in developing an
      ethical awareness and sensitivity from early in their professional development.
      This paper argues that Aristotelian virtue theory provides a practice-based focus
      for health care ethics for a number of reasons. Also, because of his emphasis on
      the character of the moral agent, and on the importance of perception and emotion
      in moral decision-making, Aristotelian virtue theory provides a useful supplement
      to the traditional duty-based approaches to health care ethics analysis, which
      are increasingly being identified in the literature as having limits to their
      application within the health care context.

PMID- 8556385
TI  - Literature, ethics and the communication of insight.
AB  - The problems of exposing students to real life situations in which they can gain
      an insight into the dilemmas experienced by clients and staff are highlighted.
      The value of the Greek notion of catharsis (katharsis: a cleansing) is discussed
      and the use of literature is suggested as a means of providing students with
      vicarious experience of the real, but often inaccessible, situations in which
      nurses may have to make moral decisions.

PMID- 8556386
TI  - Gossip, stories and friendship: confidentiality in midwifery practice.
AB  - Women often seek midwifery care as an alternative to the maternity services that
      are readily available within the insured health care system in Alberta. Some
      aspects of community-based, primary care midwifery in Alberta that characterize
      this alternative are the use of story-telling as a form of knowledge, the
      development of social connections among women seeking midwifery care, and
      nonauthoritarian relationships between midwives and women. In this paper, the
      concept of confidentiality, as it relates to these aspects of midwifery practice,
      is explored, using traditional, caring and feminist models of ethics.

PMID- 8556387
TI  - Measuring nurses' moral reasoning.
AB  - The purpose of this exploratory study was to examine the possibility of designing
      a satisfactory method, using written responses to hypothetical scenarios, for
      evaluating the quality of moral reasoning in student nurses. Scenarios were
      developed from interviews with practising nurses. Nurses and student nurses
      provided written responses to the scenarios, and nursing faculty members from six
      institutions sorted the responses according to their perceptions of quality (i.e.
      'best', 'next best', 'worst' etc.). There was very little agreement among faculty
      members on the quality of the responses. Consequently, it was impossible to
      develop a 'best' response on which the faculty members could agree. Analysis
      revealed a framework used by the participants for ethical decision-making. The
      results of this study have important implications for the way in which we think
      about the teaching and the evaluation of nursing ethics.

PMID- 8556388
TI  - Euphemisms for euthanasia.
AB  - Many patients are subject to 'do not resuscitate' orders or are 'allowed to die'.
      The predominant moral position within health care seems to be that this is
      permissible, while voluntary euthanasia is not. This paper attempts to consider
      the logic of that position. It is not intended as a case for or against voluntary
      euthanasia; those cases are made elsewhere. Instead, this is an attempt to
      challenge implicit assumptions. It is the experience of many nurses that issues
      relating to matters at the end of life are far from being resolved. This paper
      does not try to offer any practical solutions but aims at some clarification of
      the language used. This, it is hoped, will enable nurses to contribute to the
      debate.

PMID- 8556389
TI  - Psychiatric nursing and electroconvulsive therapy.
AB  - Sufficient doubt surrounds electroconvulsive therapy (ECT) to warrant nurses
      opting out of its administration and/or advising patients that it may be only one
      of a range of treatments open to them. In the latter respect, this discussion
      touches on aspects of the concept of advocacy. Relationships with the medical
      profession are also considered, as is the indefatigable attention given to issues
      of 'professional status' by nurses; this preoccupation facilitates an avoidance
      of therapeutic/advocacy issues.

PMID- 8556390
TI  - Electroconvulsive therapy, children and adolescents: the power to stop.
AB  - The administration of electroconvulsive therapy (ECT) to children and adolescents
      remains an unresolved area of clinical debate for nurses. Thus, some nurses have
      refused to participate in the treatment of minors with ECT, invoking codes of
      conduct to justify their actions. Other nurses have supported the use of ECT with
      children and adolescents, via provision of technical assistance to medical
      colleagues. A cross-national comparison of ethical codes of conduct has confirmed
      that nurses should take decisive action in the clinical arena when the needs or
      rights of vulnerable minors are compromised. The provision of clinical guidelines
      is suggested as one method to enshrine the rights of at-risk children and
      adolescents.

PMID- 8556391
TI  - Consent and the social context.
AB  - A series of eight multidisciplinary conferences on consent to health care and
      research was held in London during the period 1992 to 1995. The aim was to
      present a rich and varied account of consent from the perspectives of academics
      (especially social scientists), practitioners, and people affected by personal
      experience. This report summarizes some of the main contributions.

PMID- 8556392
TI  - Selective effects of DNA damaging agents on HIV long terminal repeat activation
      and virus replication in vitro.
AB  - Much attention has recently focused on the observation that UV light can activate
      the long terminal repeat (LTR) of the human immunodeficiency virus (HIV).
      Although the mechanism of LTR activation remains obscure, several lines of
      investigation have suggested that it is a result of activation of the NF-kappa B
      transcription factor(s) following signaling events related to generalized DNA
      damage. In this report, we present data demonstrating that HIV LTR activation is
      not a general consequence of cellular DNA damage, but rather a process unique to
      specific genotoxic stimuli, and that it does not necessarily depend on activation
      of NF-kappa B. Furthermore, we demonstrate that several of these agents can
      significantly increase HIV replication and accelerate CD4-positive lymphocyte
      cytotoxicity in vitro. These findings, therefore, could have clinical
      significance to AIDS patients with malignancies who are undergoing radiotherapy
      and chemotherapy.

PMID- 8556393
TI  - Zidovudine kinetics in the pregnant baboon.
AB  - The devastating impact of human immunodeficiency virus (HIV) infection during
      pregnancy has made the pharmacologic evaluation of potentially therapeutic agents
      of high priority. The results presented here are the maternal pharmacokinetics
      from a series of experiments to delineate more clearly the complex maternal-fetal
      pharmacokinetics and the effects of AZT in the chronically instrumented maternal
      and fetal baboon during both steady state intravenous infusion and oral bolus
      dosage regimens. Two results of major clinical importance were found. First,
      during pregnancy, both the clearance and volume of distribution of AZT were
      increased. Plasma clearance in the pregnant animals was 51 +/- 10 ml/min/kg
      compared with 37 +/- 2 ml/min/kg in the nonpregnant animals, and steady state
      volume of distribution was 3.7 +/- 1.21/kg compared with 2.2 +/- 0.61/kg. Second,
      with continuous intravenous infusion plasma drug concentrations were easily
      maintained in the therapeutic range, whereas with oral administration plasma
      concentration fell below therapeutic levels within 2 h of the dose being given.
      Because maternal plasma concentrations are a major determinant of drug
      concentration achieved in the fetus, an understanding of drug kinetics in
      pregnancy is of vital importance when making recommendations regarding optimal
      drug therapy during pregnancy to maximize the beneficial effect--the prevention
      of HIV infection in children.

PMID- 8556394
TI  - CD4+ T-lymphocyte lines developed from HIV-1-seropositive patients recognize
      different epitopes within the V3 loop.
AB  - To define the epitopes present within the V3 loop sequence recognized by five HIV
      1 envelope-specific T-cell lines, a panel of V3 LAI peptides bearing sequential
      truncations from both the N- and C-terminus was synthesized and tested for their
      ability to induce proliferation. Each individual T-cell line had a different
      pattern of response against the truncated V3 peptides, demonstrating the presence
      of a cluster of CD4+ T-cell epitopes within the V3 loop. To assess the ability of
      these envelope-specific T-cell lines to recognize and proliferate in response to
      V3 loops of different viral strains, they were tested against a panel of
      heterologous V3 loop peptides derived from different viral genotypes within and
      outside of HIV-1 clade B. There was no proliferative response against
      heterologous V3 loops by any of the lines, demonstrating that recognition of the
      V3 epitopes is highly strain specific. One of the defined epitopes was shown to
      elicit a cytotoxic response as well, suggesting the multifaceted role that the
      CD4+ T cell might play in HIV-1 disease.

PMID- 8556395
TI  - L-cycloserine, an inhibitor of sphingolipid biosynthesis, inhibits HIV-1
      cytopathic effects, replication, and infectivity.
AB  - Drugs that reduce viral production or prevent viral spread by interference with
      the host's cellular components are unlikely to induce resistance, in contrast to
      treatment modalities that interact with the HIV-1 life cycle. Two features make L
      cycloserine (L-CS) a candidate drug of this kind: (a) L-CS is a potent inhibitor
      of the sphingolipid pathway (b) sphingolipids, galactocerebrosides, and
      sulfatides have been shown, by others, to bind gp120. In a feasibility and
      efficacy study, we have found that L-CS inhibits HIV-1 replication in a CD4+
      lymphoid cell line (CEM) as documented by the reduction of syncytium formation,
      the number of HIV-1 infected cells, and p24 protein production. This observation
      may lead to a new strategy for the treatment of HIV-1 infection.

PMID- 8556397
TI  - Decisions to get HIV tested and to accept antiretroviral therapies among
      gay/bisexual men: implications for secondary prevention efforts.
AB  - The objective of this study was to report prevalence rates of adherence by HIV
      seropositive individuals to medical recommendations for the treatment of HIV
      infection, a behavioral pattern referred to as AIDS secondary prevention. We
      report cross-sectional data (n = 2,593) from two household-based and two bar
      based samples of gay/bisexual men, gathered in 1992 in Tucson, Arizona, and
      Portland, Oregon. The main outcome variables were prevalence of HIV antibody
      testing and adherence to recommended secondary prevention behaviors to prevent
      onset of AIDS symptoms. Approximately one-third of the gay/bisexual men in these
      samples do not know their current HIV status. Of the gay/bisexual men who do know
      that they are HIV-seropositive, approximately three-fourths adhere to each of the
      secondary prevention recommendations, as appropriate to their stage of disease
      progression. In a multivariate logistic model, three variables distinguished
      between HIV-seropositive men who did and did not adhere: perceived antiviral
      treatment norms (OR = 1.4, CI = 1.1-1.7), perceived efficacy of secondary
      prevention treatments (OR = 1.4, CI = 1.1-1.7), and quality of the relationship
      with one's health-care provider (OR = 2.5, CI = 1.6-4.0). These findings indicate
      that efforts to support AIDS secondary prevention behaviors can occur not only
      through health education to change the perceptions of at-risk communities about
      the options available to delay the onset of opportunistic infections among HIV
      seropositive individuals but also by enhancing effective doctor/patient
      communication.

PMID- 8556396
TI  - Long-term follow-up of symptomatic HIV-infected patients originally randomized to
      early versus later zidovudine treatment; report of a Veterans Affairs Cooperative
      Study. VA Cooperative Study Group on AIDS Treatment.
AB  - Following a 4-year controlled trial comparing early and later zidovudine
      treatment, we conducted an additional 3-year follow-up. Of the original 338
      patients, 275 participated. Clinical outcome measures were AIDS and death. In the
      early therapy group (n = 170), 67 patients progressed to AIDS compared with 85 in
      the later therapy group (n = 168); the relative risk (RR) comparing early with
      later therapy was 0.72% (95% confidence interval [CI] 0.52-0.99; p = 0.044). The
      early therapy group had 74 deaths compared with 73 in the later therapy (RR =
      0.98; 95% CI, 0.71-1.36; p = 0.91). The early group had a peak CD4+ count
      increase at 1-2 months and a delay of 1 year before CD4+ counts fell below
      baseline. For patients who received zidovudine for more than the median duration
      (20.3 months) before their first AIDS diagnosis, the RR for death was 2.08 (95%
      CI, 1.36-3.19, p = 0.001). Additional factors independently associated with poor
      prognosis following AIDS were a CD4+ count of < 100 cells/mm3 and increased
      severity of the first AIDS diagnosis, whereas use of another antiretroviral agent
      was associated with improved survival. We conclude that early zidovudine therapy
      delays progression to AIDS but does not affect survival. Patients who progress to
      AIDS while on prolonged zidovudine monotherapy many benefit from a change to
      other antiretroviral therapy(ies).

PMID- 8556398
TI  - Response of CD4 lymphocytes and clinical consequences of treatment using ddI or
      ddC in patients with advanced HIV infection.
AB  - The value of CD4 lymphocyte counts as a surrogate marker in persons with advanced
      human immunodeficiency virus infection during antiretroviral treatment was
      assessed using longitudinal models and data from the Terry Beirn Community
      Programs for Clinical Research on AIDS didanosine/zalcitabine trial of 467 HIV
      infected patients. Patients with AIDS or two CD4 counts of < or = 300 who
      fulfilled specific criteria for zidovudine intolerance or failure were randomized
      to receive either 500 mg didanosine (ddl) daily or 2.25 mg zalcitabine (ddC) per
      day. Absolute CD4 counts were recorded at study entry and at as many as four
      visits. Patients were followed for clinical disease progression and survival. At
      2 months, the difference in mean CD4 count from baseline was +15.4 cells/mm3 in
      the ddI group but -1.3 cells/mm3 in the ddC group. Patients assigned to ddI had a
      greater chance of a CD4 response at 2 months than those on ddC, yet only those in
      the ddC group with a response showed significant improvement in progression of
      disease or survival compared with ddC nonresponders, ddI responders, and ddI
      nonresponders (p = 0.03). We conclude that a CD4 response does not necessarily
      correlate with improved outcome and is therefore not a useful surrogate marker in
      these patients.

PMID- 8556399
TI  - Liver biopsy findings in 501 patients infected with human immunodeficiency virus
      (HIV).
AB  - Patients infected with human immunodeficiency virus (HIV) are at risk for a
      variety of liver diseases. We undertook a retrospective study of 501 HIV
      seropositive patients to assess the yield of percutaneous liver biopsy. The most
      common indications for liver biopsy were liver test abnormalities (89.5%), fever
      for 2 weeks (71.9%), and hepatomegaly (52.0%). The most common biopsy-derived
      diagnosis was Mycobacterium avium complex (MAC), seen in 87 (17.4%) biopsies.
      Mycobacterium tuberculosis was found in 13 biopsies (2.6%). In 28 biopsies (5.6%)
      mycobacteria was seen, but speciation of the organism was not possible. Chronic
      active viral hepatitis was seen in 60 biopsies (12.0%). Opportunistic hepatic
      infection from other organisms was found in 14 biopsies (2.8%). The most common
      neoplasm was lymphoma, which was seen in 12 biopsies (2.4%). MAC infection of the
      liver was associated with elevated alkaline phosphatase (p = 0.01). Among
      patients with fever for 2 weeks after an extensive negative workup including bone
      marrow biopsy, 58.2% had a diagnosis by liver biopsy. Overall, 64.3% of liver
      biopsies yielded a histopathological diagnosis, 45.7% of which were potentially
      treatable. We could not evaluate whether liver biopsy had a positive effect on
      patient outcome and survival, nor did we attempt to prove that liver biopsy
      resulted in a change in treatment or a change in preprocedure clinical diagnosis.
      Thus, questions about the efficacy of liver biopsy cannot be answered. Liver
      biopsy may be a helpful diagnostic tool in HIV-positive patients with fever,
      liver test abnormalities or hepatomegaly.

PMID- 8556400
TI  - Marital status in relation to Kaposi's sarcoma, non-Hodgkin's lymphoma, and anal
      cancer in the pre-AIDS era.
AB  - Persons with human immunodeficiency virus/AIDS are at high risk of Kaposi's
      sarcoma (KS), non-Hodgkin lymphoma (NHL), and possibly anal cancers. To examine
      whether this risk preceded the AIDS epidemic, we used pre-AIDS era data from the
      Surveillance, Epidemiology, and End Results program (excluding Connecticut) from
      1973 to 1976, and the Connecticut Tumor Registry from 1940 to 1976. We compared
      risk of being single (a surrogate to identify men who might be homosexual) to
      those ever married, using a case control matching study with up to 10 controls
      per case. Overall, no excess risk was observed for KS (risk ratio for men 20-59
      years old: 1.00; 95% confidence interval 0.218-3.61), but there was a suggestion
      of higher risk (4.00; 0.54-29.48) in 1973-1976, the period just before the AIDS
      epidemic. The NHL risk (0.85; 0.74-0.99) was slightly low, but for anal cancer
      the risk ratio of being single was significantly high both in men 20-59 years old
      (5.68) and older men (2.78) long before the AIDS epidemic. If the excess risk was
      solely due to being homosexual, the actual relative risk in the subset who were
      homosexual must have been much higher, given that only a fraction of the single
      men would have been homosexual. As comparison groups to verify the methodology,
      we used colon (no association with marital status) and prostatic cancer
      (decreased in single men), with findings as reported in other studies. Thus,
      single men may have been at an excess risk of KS (but a slightly low risk of NHL)
      just before the AIDS epidemic and have been at excess risk of anal cancer for
      many years before the AIDS epidemic.

PMID- 8556401
TI  - High rates of sexual contact with female sex workers, sexually transmitted
      diseases, and condom neglect among HIV-infected and uninfected men with
      tuberculosis in Abidjan, Cote d'Ivoire.
AB  - To characterize human immunodeficiency virus (HIV) risk practices among men with
      tuberculosis, and to determine what factors are associated with HIV infection in
      this population, we conducted a case-control analysis of data collected during
      enrollment in a prospective cohort study in the two large tuberculosis treatment
      centers of Abidjan, Cote d'Ivoire. Demographic information and data on risk
      factors for HIV infection, including history of sex with female sex workers
      (FSWs) and history of sexually transmitted diseases (STDs), were collected on 490
      HIV-infected and 239 HIV-uninfected men diagnosed with pulmonary tuberculosis
      between 1989 and 1992. HIV-infected men were significantly more likely than
      uninfected men to have had sex with FSWs in their lifetime [83 versus 63%, odds
      ratio (OR) 2.9, 95% confidence internal (CI) 2.0-4.2], genital ulcer disease in
      the past 5 years (38 versus 15%, OR 3.4, 95% CI 2.2-5.2), urethritis in the past
      5 years (44 versus 23%, OR 2.6, 95% CI 1.8-3.8), and sex with FSWs in the past
      year (43 versus 25%, OR 2.3, 95% CI 1.6-3.3); no difference was found in the
      proportion with at least one non-FSW partner in the past year (84 versus 79%, OR
      1.3, 95% CI 0.9-2.0). Among all men, 74% never used condoms, and only 1.4% always
      used condoms. In a multivariate analysis, sex with FSWs, genital ulcer disease,
      urethritis, and lack of circumcision were all significantly associated with HIV.
      This study demonstrates the critical roles of commercial sex, STDs, and condom
      neglect in fueling the HIV/AIDS epidemic in Abidjan, and illustrates the urgent
      need for widespread HIV education both in the general population and in men with
      tuberculosis.

PMID- 8556402
TI  - Changes in membrane enzymes and glycosphingolipids in lymphocytes from HIV-1-
      infected and noninfected intravenous drug users.
AB  - The amounts of cell-surface glycosphingolipids and plasma membrane enzymes
      produced on the peripheral blood mononuclear cells (PBMNCs) isolated from 101
      intravenous drug users (IDUs), of whom 91 were HIV-1 seropositive, were examined.
      Seronegative IDUs and age-matched healthy donors served as controls. The numbers
      of circulating CD3+, CD4+, and CD8+ T lymphocytes decreased during the advanced
      stages of the infection. There were also fewer CD4+ T-helper cells in HIV-1-
      seronegative IDU drug addicts. PBMNCs from HIV-1--seropositive subjects had
      abnormal surface enzyme kinetics. The phospholipase C had two pH optima, whereas
      the enzyme on normal cells has only one. The specific activity in cells from AIDS
      subjects was 4 times lower than that in normal PBMNCs. 5'-Nucleotidase showed a
      similar trend, whereas neutral endopeptidase activity did not correlate with the
      amounts of surface common acute lymphoblastic leukemia antigen (CALLA). These
      enzyme activities were decreased in HIV-seronegative IDUs. The subcellular
      distribution of enzymes and the profile of surface glycosphingolipids were also
      markedly changed, indicating the profound alterations in the membranes of PBMNCs
      from HIV-1--seropositive IDUs. These data suggest that intravenous drug use
      compromises the biochemical and structural integrity of the membrane surface of
      PBMNCs even before the onset of HIV.

PMID- 8556403
TI  - Psychological dysfunction and HIV/AIDS risk behavior.
AB  - The relationship between psychological problems and human immunodeficiency virus
      HIV/AIDS risk-taking behaviors was examined among 834 daily opioid users entering
      methadone treatment programs. A composite measure of psychological dysfunction
      was created using depression, anxiety, and hostility scales. This measure was
      found to be significantly related to needle risk in terms of injecting with used
      equipment, sharing of drug paraphernalia, and sharing with strangers.
      Psychological dysfunction was also related to sexual risk taking in terms of
      number of partners, unprotected sex with other injection drug users, and trading
      sex. Use of cocaine was significantly related to all measures of injection and
      sex-related risk taking; use of speedball (heroin and cocaine) was significantly
      related to use of dirty equipment and sharing of paraphernalia. The implications
      of study findings for AIDS prevention programming are discussed.

PMID- 8556404
TI  - Role of primary infection in epidemics of HIV in gay cohorts.

PMID- 8556405
TI  - p24 antigenemia in African patients during primary HIV infection.

PMID- 8556406
TI  - Using HIV/AIDS surveillance to monitor public health efforts to reduce perinatal
      transmission of HIV.

PMID- 8556407
TI  - 14-year follow-up of HIV-infected homosexual men with lymphadenopathy syndrome.

PMID- 8556408
TI  - HIV seroprevalence study among 729 female prostitutes in Italy.

PMID- 8556409
TI  - [Withdrawal in opiate addicts in an internal medicine hospital unit].
AB  - Withdrawal of opiates drug addicts in Internal Medicine is unusual in France.
      Four main preliminary conditions are requested: 1--Drug addict preparation and
      self motivation, 2--Inter and intra institution team collaboration, 3--Opening
      the hospital towards community agencies, 4--Hospital staff recruited on volunteer
      basis. Within two years (1992-1993), 210 opiates drug addicts were hospitalized
      for withdrawal. Two third were males, median age was 27, median years of
      addiction was 7. Thirty percent were seropositive for HIV, 70% for HCV.
      Hospitalisation lasted 7 days for heroin addicts and 10 days for morphin, codein
      or buprenorphin addicts. Successful withdrawn was observed for 70% patients but
      six months after withdrawal, only 15% remained abstinent.

PMID- 8556410
TI  - [Dysfunction of the aldosterone synthesis pathway as a marker of malignity in
      symptomatic and asymptomatic adrenal masses].
AB  - Fundamental research performed in the author's laboratory led to the
      understanding of mechanisms of the mineralocorticoid biosynthetic pathway.
      Sensitive assays were then developed to allow measurement of the different
      mineralocorticoid metabolites in several biological fluids. Using these methods
      biological markers that contribute to the differential diagnosis between benign
      and malignant adrenal tumors were identified. In the present paper we report that
      the exploration of the entire mineralocorticoid pathway in the plasma of patients
      during basal state and after stimulation and/or inhibition test is a powerful
      tool to predict or validate diagnosis of adrenal malignancy. Moreover,
      mineralocorticoid exploration can help differentiate between two different types
      of malignancy, ie malignant cortical adrenaloma and metastases of other cancer.
      The biochemical mechanisms leading to the atypical mineralocorticoid metabolism
      in the case of malignant cortical adrenaloma are now under study.

PMID- 8556411
TI  - [Eulogy of Jerome Lejeune (1926-1994)].

PMID- 8556412
TI  - [In vitro induction of apoptosis in chronic lymphoid leukemia B lymphocytes by
      theophylline: therapeutic applications].
AB  - In a case of indolent stage A chronic lymphocytic leukemia (C.L.L.), treated for
      ten years only by theophylline for bronchial asthma, we observed spontaneous
      apoptosis of B lymphocytes (10%). As suggested by these case report, we described
      new properties of methylxanthine derivatives. In vitro, theophylline increased
      spontaneous apoptosis after 72 hours in culture of 6 patients by a mean
      percentage of 80-90% in B-C.L.L. blood lymphocytes (control 20%). Dose-dependent
      apoptosis involves cyclic nucleotides (AMPc). Using identical theophylline doses,
      we did not observe apoptosis of normal peripheral blood B lymphocytes. According
      to French ethical rules, we treated 8 patients with the same doses of
      theophylline than for bronchial asthma without responses. On the other hand, in
      12 aggressive forms of C.L.L., resistant or in relapsed after alkylating agents,
      methylxanthine derivatives appeared a powerful adjuvant of chlorambucil
      treatment. We observed 11 responses with less dose of alkylating agents than in
      previous treatment: decrease in the concentration of blood lymphocytes (11
      patients) and clinical remissions (8 patients). Mechanism of action and future of
      this new drugs combination in the treatment of C.L.L. are discussed.

PMID- 8556413
TI  - [Lead in drinking water, determination of its concentration and effects of new
      recommendations of the World Health Organization (WHO) on public and private
      networks management].
AB  - In 1993, the World Health Organization (WHO) has given a guideline value of 10
      microgram/l for lead in drinking water, a phased approach should lead to a
      temporary parametric value of 25 micrograms/l within 5 years the final
      concentration value of 10 micrograms/l being achieved after 15 years. So far the
      current European Community Directive 80/778 and the French decree 89/3 stipulate
      a Maximum Admissible Concentration (MAC) for lead of 50 micrograms/l. In a first
      step we studied the mechanisms of plumbosolvency in corrosive and scaling water.
      In the first case we have shown that simple oxidative corrosion of lead pipes
      forms a coating of lead carbonate and hydroxicarbonate on the inside wall of the
      pipe but "plumbosolvent" waters can dissolve those products, although at a lower
      level, resulting in a rather high lead concentration. In the case of scaling
      waters there is a co-precipitation of insoluble calcium carbonate but only on the
      microcathodics zones of the lead pipe. As this precipitate is poorly cohesive and
      does not cover the entire surface of the pipe its oxidative corrosion can
      proceed. In a second step we have shown the major importance of sampling for the
      determination of lead concentration in drinking water. We therefore compared
      random day time sampling, first draw and flushed samplings and composite
      proportional sampling. Only this last method gave a reasonably accurate idea of
      lead's amounts ingested by drinking water's consumers. The control of corrosion
      in lead-containing materials involves two successive steps: the reduction of lead
      concentration to 25 micrograms/l within five years and the compliance with the
      final 10 micrograms/l concentration 15 years later. The first step consists in
      water treatments such as pH increase, adjustment of alkalinity and addition of
      orthophospates. But available data suggest that it is unlikely that lead
      concentration could be reduced consistently to below 10 micrograms/l by avalable
      water treatment methods alone but it would enable to match the parametric 25
      micrograms/l value in the great majority of cases. Therefore, to unable
      compliance with the 10 micrograms/l parametric value, it will be necessary to
      replace all the internal plumbing and supply lead pipes (70,000 buildings for
      Paris only). Data for materials able to replace lead such as plastic pipes are
      not yet complete and an currently under investigations. Although the United
      States Environmental Protection Agency have suggested in its 1988 report on air
      quality criteria for lead report (EPA 600/8-33-028 aF-dF) that each 1 microgram/l
      of lead in water can lead to an increase of blood lead levels of approximately
      0.2 micrograms/l for a child, the data are still uncertain. The considerable cost
      of these works (143 billion of french francs for France and 347 billions of
      french francs for Europe), unrelated to any important Public Health problems,
      arises an ethical problem which has to be considered in view of many others letal
      illnesses such as heart and circulatory diseases, cancer and AIDS.

PMID- 8556414
TI  - [Information on the Federation of National Academies of Medicine and similar
      institutions of the European Union].

PMID- 8556415
TI  - [Introduction to the session on the subject: physical activities and health].

PMID- 8556416
TI  - [Role of physical activities in a public health policy].
AB  - A gradual decrease in energy output for adults in the Western countries has been
      observed through the XXth century. The mechanization in industrial societies
      result in a decline of customary physical activity and consequently in the
      potentially vicious spiral of inactivity leading to deconditioning and thence,
      via loss of physiological capacity, to a further reduction in activity. The
      sedentary life has injurious effects on the health of individuals and specially
      increase the risks of cardiovascular disease. Furthermore there is a supposed
      relation between inactivity with obesity and hyperlipemia in young people and
      with osteoporosis in elderly. In contrast, many papers showed that high levels of
      physical activity have been associated with a diminished occurrence of
      hypertension, coronary artery disease, non insulin-dependent diabetes, colon
      cancers... In addition physical fitness is obviously related to the quality of
      life. Because of all these reasons several developed countries have elaborated
      plans of physical reconditioning for their people. In France some experimental
      actions have been completed but any national programme has been determined.
      Moreover it is now crucial to promote scientific researches about the fundamental
      biological mechanisms which explain the beneficial effects of physical training
      on the prevention and/or the treatment of several illness.

PMID- 8556417
TI  - [Physical activities and health: results of a national survey of workers].
AB  - Since 15 years, the ASMT (Association for the promotion of sports in enterprises)
      has been trying to demonstrate that physical activities is a health factor for
      workers and their enterprises. Few studies (1980-1990) in individual enterprises
      (Alsthom, IBM, Aerospatiale, Peugeot...), and a national one (1985, 1,600
      sportsmen) have shown the relationship between exercise and a lower absenteeism.
      These results were confirmed by a randomized national controlled study in 1990
      1991. With the assistance of 115 work-doctors, the ASMT included more than 22,000
      workers: 38% of them had physical activities (ASMT 1: 1 hour a week, ASMT 2: 3
      hours a week, ASMT 3: competitors), and 62% had none. Exercisers have less
      industrial injuries than sedentary people (3.78% vs 4.52%. p. < 0.001) and less
      absences for illness (26.4% vs 30.8%. p. < 0.001). The duration of their absences
      are shorter for industrial injuries (sedentary people: 27.9 days, ASMT 1: 27.1
      days, ASMT 2: 25.5 days, ASMT 3: 24.6 days) and for illness (sedentary people:
      23.6 days, ASMT 1: 19.1 days, ASMT 2: 17.4 days, ASMT 3: 15.3 days).

PMID- 8556418
TI  - [Role of sports in Army-Nation relations].
AB  - Sports have very old and frequent ties between the nation and the army. Relations
      can be very tight as in ancient Greece, variable in time in a same country,
      different during the same period in neighbouring countries. Sport was probably
      introduced as a witness of certain countries power behind which people get
      together and recognise themselves. More often in the history of nations they
      found in physical activities the means to restore the sense of effort and that of
      health. In these ventures, the army has brought it's contribution by putting in
      place structures and establishments; participating in this way for general
      liveliness even if it was sometimes criticized. Health, which is often the
      argument used during the installation of sports programs, justifies inquiries and
      scientific works. In this field also, the army; by it's health service intervenes
      particularly in a large numbers or for other activities concerning extreme
      situations. In other respects, sports and health should figure in the global
      defence of a nation.

PMID- 8556419
TI  - [Hormonal response and adaptation to short-term exercise and training].
AB  - Physical exercise induces a mobilization of energy substrates in order to furnish
      fuel for metabolic pathways. A part of this regulation is under hormonal
      influences. A decrease in plasma insulin and an increase in catecholamines play a
      central role. It results an enhanced lipolysis. The increase in insulin
      sensitivity favours muscle glucose consumption in spite of hypoinsulinemia during
      exercise. These coordinated actions indicate that physical training is able to
      influence the mechanisms of type 2 diabetes with insulin resistance when the
      etiology of type 1 diabetes is not influenced by physical training. Physical
      exercise exerts a synergic effect with diet in the treatment of obesity but it is
      inefficient alone. The action of physical training on metabolic disease is
      related to the level and duration of training.

PMID- 8556420
TI  - [Physical activity and cardiorespiratory equilibrium].
AB  - Nowadays it is believed that each patient can participate in a physical activity
      adapted to his or her pathology, based on a rationale. In cardiorespiratory
      patients, the crucial point is an excessive hyperventilation at submaximal
      exercise. The "dyspnea spiral" is a good model for understanding this particular
      response. The lung and cardiac function impairment induces dyspnea during
      moderate exercise. To avoid this dyspnea, the patient develops a sedentary
      lifestyle which induces deconditioning, i.e., regression of the aerobic pathway.
      For a given load, anaerobic glycolysis plays an increasingly important role. This
      leads to an increase in blood lactate concentration during exercise. The
      buffering of lactic acidosis by blood bicarbonate produces an additional amount
      of CO2, and results in a proportional increase in ventilation requirement, which
      increases dyspnea. The patient again decreases his physical activity, and the
      downward spiral continues. Thus in cardiorespiratory patients dyspnea has two
      origins. The primary disease is the heart or lung disease. The deconditioning is
      a true secondary disease. The aim of exercise training in cardiorespiratory
      patients is to treat secondary disease in order to relieve dyspnea, and increase
      exercise tolerance and therefore quality of life. Training sessions usually last
      45 minutes, two or three times a week, at the intensity of anaerobic threshold,
      this latter being more precise and individualized than an arbitrary percentage of
      maximal heart rate. The results show a decrease in ventilation at submaximal
      level of exercise up to 20-30% with a systematic alleviation of dyspnea and an
      increase in exercise tolerance and in quality of life. Exercise training in
      considered to be the best treatment of dyspnea in cardiorespiratory patients.

PMID- 8556421
TI  - [Physical training and blood pressure].
AB  - The effects of exercise training on blood pressure (BP) are reviewed. BP rises
      during exercise and lowers in the post-exercise period. Regular physical training
      result in a significant lowering of BP at rest as long as the training is
      continued. Moreover exercise training result in a BP lowering during exercise
      which is greater in hypertensive patients than in normotensive subjects. A
      favourable effect is observed also on ambulatory blood pressure, but the night
      time blood pressure is not lowered. The mechanisms of training-induced changes of
      BP are not sufficiently known. The exercise training seems act on systemic
      vascular resistance, plasma catecholamine, PGE2 and taurine levels, renin
      angiotensin-aldosterone system. As adequate physical training can reduce BP, we
      can consider it is a non pharmacological treatment of hypertension: mainly for
      border lines, labile and mild hypertensives patients. For certain hypertensive
      patients, some sports can be permitted when no target organ is involved.

PMID- 8556422
TI  - [Physical activities and bone mass in women].
AB  - The mechanism and its effects on the bone mass are discussed. The bone disorders
      of spacemen show the necessity of physical constraints. The intensive physical
      exercise can increase disturbances in the bone remodeling. But the hormonal
      disorders (amenorrhea, oligomenorrhea) which are made by intensive and top level
      physical activities, increase indirectly the bone remodeling and decrease the
      bone mass. The effects of a moderate physical activity are more discussed.
      Nevertheless, an increasing of the bone mass peak is admitted. In the adult and
      postmenopausal women, the data are more uncertain and discussed. But, an adapted
      moderate regular physical activity for each people authorizes certainly a bone
      gain. It is favorable to prevent osteoporosis, its fractures and reduce the
      social cost.

PMID- 8556423
TI  - [Physical and sports activities and aging: how to delay the state of dependence].
AB  - The ageing is a daily physical activity's reduction and after 80 years can led to
      dependence. The physiological factors of this evolution are: reduction of
      striated muscular mass, reduction of cardiac output, reduction of VO2 max from 50
      ml.min-1.kg-1 at 30 years to 20 ml.min-1.kg-1 at 80 years. On average the
      reduction of moving functional capacity in 10% by decade. The studies show in
      fact that the half of reduction is due to ageing, and the other half to sedentary
      life. The lower limit is 15 ml.min-1.kg-1, threshold of dependence; it is an
      expensive and irreversible stage. To slow down the dependent people's number, it
      is one alone way: physical and sports activity in endurance from 55 years. With
      these exercise and method, the dependence is put back 10 or 20 years for anyone.
      We prevent the fact that we do not know cure.

PMID- 8556424
TI  - [Teaching digestive laparoscopic surgery in France: from education to
      accreditation?].
AB  - The extremely rapid development of laparoscopic surgery since 1989 has given
      evidence, by the increase in the number of local and vital complications, that
      teaching of laparoscopic surgery is absolutely necessary, especially technical
      and practical training. Indeed, laparoscopic surgery is not only a new and
      different way to attain abdominal organs, but it needs also a complete different
      acquiring of gestures, which are difficult since the eyes and hands are
      dissociated due to the videotechnics. The University post-graduate training
      courses (University Diploma D.U.), which were first organized by the authors in
      Paris and Nice since 1990, have given the best answers to this challenge:
      training a large number of surgeons in a minimum of time. In 1994, a new College
      of general visceral and digestive surgeons was founded and the teaching
      conditions have been modified since. This college courses of general and
      digestive surgery (D.E.S and D.E.S.C respectively) and during post-graduate
      formation (F.M.C). After having given recommendations for the program of
      theoretical and practical teaching of laparoscopic surgery, the authors suggest
      that this teaching should be integrated in graduate courses of general surgery
      and in post-graduate courses. These courses represent the best training and are
      the guarantee of good quality and it would be a big error to suppress them. They
      should continue under the constant control of the French College of Digestive
      Surgeons and be supervised by the French National order of medical Doctors.

PMID- 8556425
TI  - [Morphometry by analysis of microcalcifications and histopathological diagnosis:
      a new approach to the diagnosis of impalpable lesions of the breast detected by
      mammography].
AB  - A series of 104 impalpable breast lesions detected by mammograms containing
      microcalcifications was studied. Intraoperative radiographs of intact and sliced
      specimens were assessed, followed by microscopic diagnostic on frozen sections of
      areas containing microcalcifications. Microcalcification detected on mammograms
      and on radiographs of the specimens were digitized and evaluated according
      morphometric parameters including the mean surface, shape factor, bend energy,
      the envelope surface and the total surface, the total number and the
      concentration of the microcalcifications. Benign disorders, atypical hyperplasia
      and carcinomas accounted for 47.2%, 4.8% and 48% of the tissue lesions
      respectively, but disorders were most often heterogeneous and mixed. Most but not
      all parameters were significantly correlated in the three types of radiographs,
      although radiographs of the sliced specimens provided for images of the best
      quality. Only two parameters, the mean size and the bend energy were
      significantly (p = 0.008, p. = 0.036) different in benign and malignant lesions.
      It is concluded that image analysis of digitized microcalcifications in
      radiographs may provide a quantitative basis helpful for mammograms
      interpretation.

PMID- 8556426
TI  - A new method for designing PCR primers specific for groups of sequences and its
      application to plant viruses.
AB  - A new method is described for identifying short regions of sequence similarity in
      a group of selected sequences. These regions have been used for the design of
      both specific and degenerate PCR primers for the detection of groups of plant
      viruses, but the method has wider applications. The method is an extension of the
      GCG programs COMPARE and DOTPLOT, so the name "dot primers" is suggested as a
      generic term for primers designed in this way. The method described is more
      direct and more efficient than current methods that use sequence alignment
      algorithms.

PMID- 8556427
TI  - Gene transfer by jet injection into differentiated tissues of living animals and
      in organ culture.
AB  - Jet injection can be used to introduce genes into the cells of differentiated
      tissues of living animals and organ cultures. When a solution of plasmid DNA is
      jet injected into a selected tissue or organ, cells lying in or near the path of
      the jet injection are transfected with the DNA and the introduced gene(s) are
      expressed. Since there is minimal morbidity from each jet injection, multiple
      injections can be performed at the same or nearby sites. Both mRNA and protein
      expression from transfected genes can be quantitated using standard methods. In
      addition, the technique is an efficient means of DNA immunization. Methodology
      for using jet injection to transfer plasmid DNA into the cells of skin, fat,
      mammary gland, and muscle are described.

PMID- 8556428
TI  - Applications of electroporation of adherent cells in situ, on a partly conductive
      slide.
AB  - Nontraumatic, simple, and reproducible procedures for the introduction of
      nonpermeant molecules into adherent mammalian cells by in situ electroporation
      are described. Cells are grown on a glass slide, half of which is coated with
      electrically conductive, optically transparent, indium-tin oxide. An electric
      pulse is applied in the presence of the molecules to be introduced, and their
      effect on the cellular phenotype can be observed. The cells growing on the
      nonconductive side of the slide do not receive any pulse and serve as controls.
      Careful adjustment of electric field strength can achieve the introduction of the
      molecules into essentially 100% of the cells, and this treatment causes no
      detectable disruption to cellular metabolism. This is applied in the presence of
      the fluorescent dye, Lucifer yellow, causing its penetration into the cells
      growing on the conductive half of the slide. The migration of the dye to the
      nonelectroporated cells growing on the nonconductive area is microscopically
      observed under fluorescence illumination.

PMID- 8556429
TI  - The synthesis and compositional analysis of phosphopeptides.
AB  - Protein phosphorylation plays a critical role in the regulation of cell growth
      and differentiation. There is considerable interest, therefore, in the facile
      synthesis of peptides that possess selectively phosphorylated residues for use as
      molecular probes in mechanistic studies of the biological consequences of
      phosphorylation. This work will review the various synthetic protocols used in
      the generation of phosphopeptides and will discuss their characterization by
      amino acid compositional analysis.

PMID- 8556430
TI  - A review of protein engineering for the food industry.
AB  - In this review I briefly describe the technique of protein engineering and
      indicate how the present state of knowledge allows proteins to be mutated to
      increase or decrease stability. I discuss experiments on both model proteins and
      those of relevance to the food industry and show how hydrophobic forces are a
      major driving force for folding as well as having a major role in
      thermostability. I also indicate the large contribution that hydrogen bonding,
      electrostatic interactions and, in a less well predicted way, disulfide bridges
      make to thermostability.

PMID- 8556431
TI  - The commercial and agricultural applications of animal transgenesis.
AB  - The potential for commercial application of transgenic technologies in domestic
      animals is discussed in relation to the areas where a significant impact on
      agriculture might be expected. These are the endocrine system, novel biochemical
      pathways, structural proteins of milk and of textile fibers, and the immune
      system. Manipulation of the endocrine system has been investigated for some years
      and it is clear that very accurate control is needed over gene expression if this
      approach is to prove commercially useful. The area most advanced in commercial
      application is the production of high-value pharmaceutical proteins in the
      mammary glands of domestic animals. Other applications that are discussed remain
      to be proven in larger animals despite being demonstrated laboratory test
      animals. These include a functional cysteine biosynthetic pathway and a
      functional glyoxylate cycle transferred from bacteria to mice, and alterations to
      the proteins of hair that change the physical properties of the resultant fibers.
      Research is also actively directed toward novel approaches for providing domestic
      animals with resistance to insects.

PMID- 8556432
TI  - Principles and methods for the analysis and purification of synthetic
      deoxyribonucleotides by high-performance liquid chromatography.
AB  - The need for high-purity oligodeoxyribonucleotides for various applications has
      resulted in the development of novel synthesis, purification, and analytical
      techniques. A diversity of methods, including polyacrylamide slab gel
      electrophoresis, capillary gel electrophoresis, as well as high-performance
      liquid chromatography (HPLC), have been successfully used to aid in the
      characterization and isolation of these synthetic compounds. The information
      contained in this review article primarily details both the theoretical and
      practical aspects related to the use of HPLC for the analysis and purification of
      synthetic DNA. In addition, a variety of postsynthesis sample preparation
      protocols, commonly employed prior to and after HPLC, are described.

PMID- 8556433
TI  - Depression and maltreatment as predictors of social competence and social problem
      solving skills in school-age children.
AB  - Childhood depression and child maltreatment have been shown to be important
      predictors of childhood adjustment problems, including difficulties in the
      spheres of home, school, and peer relationships. In this study, depression and
      maltreatment were used to predict social competence and social problem-solving
      skills, as rated by self, parent, and teacher. The total sample contained 68
      children (35 girls, 33 boys), most of whom were at high-risk either due to
      poverty, physical abuse and neglect (as determined by substantiated Protective
      Services reports), or exposure to negative life events. Hierarchical multivariate
      regression analyses were used to identify the contribution of depression and
      maltreatment to social competence and social problem-solving skills. Depression
      predicted parents' and teachers' ratings of social competence and parents'
      ratings of peer rejection. Additionally, depression predicted children's ratings
      of social competence and both measures of social problem-solving skills.
      Maltreatment predicted parents' and teachers' ratings of social competence.
      Gender predicted teachers' ratings of peer rejection and social competence. An
      additive effect of depression and maltreatment was found such that children who
      are depressed and maltreated have the lowest social competence as rated by
      parents and teachers. These children are, therefore, doubly at risk for problems
      in future relationships.

PMID- 8556434
TI  - The impact of the peace treaty on psychological well-being: a follow-up study of
      Palestinian children.
AB  - This research examined the impact of the Israeli-Palestinian peace treaty and
      Palestinian children's perception of it on their self-esteem and neuroticism. We
      also studied the relative importance of earlier exposure to traumatic experiences
      and psychosocial resources indicated by the children's creativity, intelligence
      and political activity in influencing their psychological well-being after the
      peace treaty. The sample used was a follow-up group of 64 Palestinian children of
      11-12 years of age, living in the Gaza Strip. The results showed that the level
      of neuroticism was significantly lower after the peace treaty than before. The
      children's earlier exposure to traumatic experiences was still significantly
      related to high neuroticism and low self-esteem after the peace treaty.
      Acceptance of the treaty and participating in the subsequent festivities
      mitigated the negative impact of the traumatic experiences on their well-being.
      Increased neuroticism and decreased self-esteem were found only among children
      who refused to accept the peace treaty and did not participate in the
      festivities. Creativity and Intifada activity promoted their post-peace treaty
      well-being, in terms of psychosocial resources. The more creative the children
      were, the more their neurotic symptoms decreased because of the treaty and the
      higher self-esteem they had after it. The more active the children were during
      the Intifada, the more their self-esteem increased because of the treaty.

PMID- 8556435
TI  - Child maltreatment as perceived by Arab students of social science in the West
      Bank.
AB  - There is a dearth of knowledge about the problem of child maltreatment in Arab
      societies. In the West Bank and Gaza Strip, the Palestinians are facing the
      challenge of establishing their own social welfare system as a result of signing
      the Declaration of Principles with Israel. In creating services for families and
      children, the helping professionals in these areas find that one of the main
      challenges is to integrate and apply knowledge accumulated in Western countries
      into a different sociocultural context. Another challenge is to develop knowledge
      on this subject congruent with their own cultural background. Because of this
      lack of knowledge, a study was conducted among 353 students in the helping
      professions in the West Bank. An instrument constructed for this study was
      utilized to examine the following subjects: (a) students' perceptions of
      situations of child maltreatment; (b) their awareness of signs of maltreated
      children; (c) their awareness of risk factors which could be related to this
      problem; and (d) their willingness to report cases of child maltreatment. The
      results indicate a high level of agreement among students in viewing situations
      of abuse as well as neglect as maltreatment. Differences were found in their
      willingness to report situations of maltreatment. A higher tendency was found to
      report situations of abuse rather than neglect. An inclination was found among
      students to minimize social and cultural factors as risk factors and to disregard
      signs that did not contain explicit signals of danger as characteristics of
      maltreated children. Implications for the development of services in Arab
      societies are discussed.

PMID- 8556436
TI  - Using spoken attributions to classify abusive families.
AB  - Despite claims that beliefs held by abusive parents are important indicators of
      family functioning, few studies have explored the relationship between patterns
      of beliefs and severity of abuse. This study applies findings from marital
      research that demonstrate that maladaptive attributional patterns predict the
      level of distress experienced in adult relationships. It examines spoken
      attributions produced by 18 families during diagnostic therapy sessions following
      serious abuse of a child. Attributions were identified from transcripts and coded
      using a standard system. Patterns of attributions, defined on the basis of
      previous work, successfully predicted classification of families by therapists as
      Good, Uncertain, and Poor, in terms of prognosis for rehabilitation. Using this
      classification to test hypotheses based on attributional style, group differences
      were found. In families rated Good, parents were more likely to attribute more
      control to self than child for negative outcomes. They were also more likely to
      nominate themselves as causing negative events. Case accounts of families from
      each category are presented to illustrate how attributional analysis can
      contribute to an understanding of the individual nature of child abuse.

PMID- 8556437
TI  - Marital disruption--the welfare of the children thereafter in Nigeria.
AB  - Departure from the traditional society is being witnessed in Nigeria and many
      cultural values and control are being lost. Many marriages are contracted between
      the individuals as opposed to between families, and so poorly withstand the test
      of time and stress of modern day living, hence more children witness family
      disruption than before. One thousand randomly selected State Social Welfare case
      records were studied in depth and information regarding the socioeconomic and
      demographic characteristics of the families, the nature of their problems,
      welfare status of the children including paternal contribution for their
      maintenance were extracted, collated and analyzed. Some important variables were
      also cross-tabulated. Young maternal age was found to statistically influence the
      type of case/nature of complaint and the living arrangement of the children (p =
      .001 and p = .00035 respectively). Income level of the mother also affected the
      type of case/nature of complaint significantly (p = .00001). About 53.6% of the
      cases were for maintenance and 23.1% for custody. Most of the children were
      underage; 56.8% of the first born were under 5 years of age. Single custody was
      commonly practiced, 63.6% of the children lived with their mothers only and 10.2%
      with their fathers only before intervention, thereafter 16 of those living with
      their mothers only were transferred to their fathers. Only .09% of the women
      remarried and about half of these women had children from their previous
      marriages living with them; some had their new husbands helping with maintenance.
      Many of the biological fathers were not responsible for the maintenance of their
      children and the few that were defaulted regularly. The mothers had to seek
      redress; the steps taken included social welfare intervention (95.5%), police and
      legal (4%), and family intervention (0.3%). The inadequacy, inappropriateness,
      and obsolete nature of our social laws were highlighted by this study. Therefore,
      urgent attempts at revising and reforming them in line with the demands of the
      society vis-a-vis our level of development and improving standards of living are
      strongly recommended.

PMID- 8556438
TI  - Clinical characteristics related to severity of sexual abuse: a study of
      seriously mentally ill youth.
AB  - OBJECTIVE: In this study we examined demographic, social, and clinical variables
      related to sexual abuse histories in a sample of severely mentally ill youth.
      METHOD: Data were collected via a retrospective chart review of all patients
      treated over a 5-year period (1987-1992) at a tertiary care public sector
      psychiatric hospital. The sample was divided into four groups: no history of
      sexual abuse (n = 226); isolated events (n = 62); intermittent abuse (n = 61);
      and chronic (n = 150). RESULTS: Youth with sexual abuse histories were more often
      female, had higher rates of social chaos and associated physical abuse and
      neglect, and had higher rates of post-traumatic stress disorder (PTSD) and
      substance abuse disorders. Chronically abused subjects came from the most chaotic
      and abusive backgrounds; were younger when first abused; had the highest number
      of abusers; were more likely to have been molested; and were more often abused by
      their father/stepfather and/or their mother/stepmother. Using logistic regression
      analyses, sexual abuse histories were predicted by sexually inappropriate
      behaviors, symptoms of PTSD and borderline personality disorders, dissociative
      symptoms, substance abuse and animal cruelty. CONCLUSION: Sexual abuse histories
      were quite common in this sample. Sexually abused subjects had increased rates of
      inappropriate sexual behaviors, substance abuse, and post-traumatic reactions;
      and were frequently exposed to other confounding environmental risk factors,
      including physical abuse, family problems and social chaos.

PMID- 8556439
TI  - Evidence for specific effects of childhood sexual abuse on mental well-being and
      physical self-esteem.
AB  - Women who are sexually abused are at increased risk for having mental health
      problems long after the abuse. Other nonexploitive experiences can also be
      psychologically detrimental, may coexist with sexual abuse, and may explain some
      portion of subsequent mental health problems. This study addresses the
      association between childhood sexual abuse and a woman's psychological
      functioning, independent of the quality of parental nurturance received during
      childhood and other variables which may influence mental health. Of 609 women
      completing mental health and self-concept measures, 98 reported sexual abuse; 110
      of the remaining women were selected as comparisons. Women sexually abused as
      children scored lower on measures of mental health status. Both sexual abuse and
      fewer years of education were related to lower scores on a psychological well
      being scale after variance accounted for by family and demographic variables was
      removed. Sexual abuse was not a predictor of general self-concept scores after
      the removal of family and demographic variables, but sexual abuse was
      independently associated with the subscale measuring the physical aspect of self
      concept. These findings lend support to theorized causal links between child
      sexual abuse and some aspects of later psychological difficulties.

PMID- 8556440
TI  - Evaluation of children's sexual behaviors and incorporation of base rates in
      judgments of sexual abuse.
AB  - One hundred sixty-one professionals and 97 undergraduates were asked to (a)
      prioritize 12 hypothetical CPS cases on the basis of sexual behaviors displayed
      by children, and (b) estimate the probability of abuse in a single case involving
      a child who had displayed sexual behavior and came from a population with a known
      base rate of abuse. When asked to prioritize the 12 cases as "high," "medium," or
      "low" on the basis of sexual behaviors, professionals were more accurate than
      students. However, when asked to estimate the probability of abuse in the single
      case, both professionals and students failed to incorporate base rate information
      into their decisions. As a result, both groups misestimated the probability of
      abuse under some circumstances. Professionals' performance on both judgment tasks
      was unrelated to level of experience with sexual abuse cases.

PMID- 8556441
TI  - Incest revisited: delayed post-traumatic stress disorder in mothers following the
      sexual abuse of their children.
AB  - The case histories of four women who developed symptoms of post-traumatic stress
      disorder following the disclosure of the sexual abuse of their daughters are
      presented. These individuals also exhibited comorbid symptoms of depression and
      personality disorders. Awareness of the sexual abuse of their daughters catalyzed
      a reliving of their own childhood victimization. The psychodynamics operating in
      these cases, as well as treatment strategies are also presented. A brief follow
      up of three of the four cases is included.

PMID- 8556443
TI  - The effects of forced sexual intercourse on white female adolescents.
AB  - In the 1987 National Survey of Children the question was asked: "Was there ever a
      time when you were forced to have sex against your will, or were you raped?"
      Among White females, aged 18-22, those who answered yes (n = 41) and no (n = 400)
      were compared on a number of social-psychological and sexual variables that might
      be thought of as outcomes affected by having had coercive sexual experience(s).
      Those who reported being forced to have sexual intercourse, compared to those who
      did not, had more permissive attitudes about 16-17-year-olds having intercourse
      and a younger age of first voluntary sexual intercourse themselves. They also had
      lower internal locus of control and higher depression scores, and they needed and
      received more psychological help than those not reporting forced sexual
      intercourse. Dividing the forced sexual intercourse group (FSI) into those
      reporting FSI before versus after their first date, and those whose FSI was
      before versus after age 12, yielded essentially the same findings. Even in the
      presence of multivariate control variables. FSI experience remained a significant
      predictor of age at first voluntary sexual intercourse, locus of control,
      depression, and perceived need for psychological help. These analyses of national
      survey data support the clinical perspective that forced sexual intercourse
      causes or exacerbates various sexual and psychological problems.

PMID- 8556442
TI  - Are adolescents who report prior sexual abuse at higher risk for pregnancy?
AB  - Adolescents who report prior sexual abuse are at increased risk for adolescent
      pregnancy. This may result from earlier, more frequent, less well-protected
      sexual activity or from a greater desire to conceive. To determine the relative
      contribution of these two possible explanations to the reported association
      between sexual abuse and adolescent pregnancy, we studied the reproductive and
      sexual histories of 200 sexually active 13-18 year old females in relation to
      self-reported sexual abuse. Anonymous questionnaires revealed that 40 (20%) of
      the 200 subjects reported sexual abuse. Analyses revealed no group differences in
      the median age of first voluntary intercourse, the frequency of sexual
      intercourse, or the consistency of birth control use. Compared to their nonabused
      peers, however, teenagers reporting abuse were more likely to be trying to
      conceive (35% vs. 14% p < .01), to have boyfriends pressuring them to conceive
      (76% vs. 44% p < .01), and to have fears about infertility (38% vs. 16% p < .01).
      Our findings suggest that childhood sexual abuse may increase the risk of
      adolescent pregnancy by fostering the desire to conceive. Further study is needed
      to determine why a disproportionate number of sexually abused adolescents desire
      pregnancy. The efficacy of adolescent pregnancy prevention programs may be
      improved by identifying previously abused adolescents and by designing
      educational interventions that specifically address their desire to conceive.

PMID- 8556444
TI  - Sexually transmitted diseases in children and evidence of sexual abuse.
AB  - During the period June 1989 to March 1991, laboratory evidence of sexually
      transmitted diseases (STDs) was found in 107 patients at the Red Cross War
      Memorial Children's Hospital in Cape Town. Data was available on 96 patients aged
      23 months to 14 years (mean 75.9 months). Vaginal discharge was the most frequent
      presenting symptom (76%), particularly in those less than 5 years of age (90%).
      Although a history of abuse was not given on presentation in 62%, evidence of
      abuse was subsequently elicited in 67% of patients. Neisseria gonorrhoeae was the
      most common sexual pathogen (61 isolates, 8 penicillin resistant), followed by G
      vaginalis (17 isolates), Trichomonas vaginalis (7 infections), and T pallidum (9
      TPHA positive, 5 with VDRL 1:4 or higher). Chlamydia trachomatis was demonstrated
      by immunofluorescence in 14 children. Multiple STDs were demonstrated in 10
      patients. Although evidence of CSA was not found in all patients with STDs it was
      likely that the vast majority of patients had acquired these infections by CSA.
      Symptomatic prepubertal children with G vaginalis isolates should be investigated
      for CSA. Chlamydial immunofluorescence tests did not assist the diagnosis of CSA
      in children and should not be used, as they have no medicolegal significance.

PMID- 8556445
TI  - Commentary on "Incest revisited: delayed post-traumatic stress disorder in
      mothers following the sexual abuse of their children".

PMID- 8556446
TI  - DNA-DNA interaction in thin layer analysed by cryo-electron microscopy.
AB  - Thin vitrified films of 146 base pair double-stranded DNA fragments in semi
      dilute solutions are observed by cryo-electron microscopy. Depending on the salt
      conditions of the buffer and the DNA concentration, the molecules form different
      characteristic arrangements: they are arranged either locally parallel to each
      other in random overall orientation or packed perpendicular to the film surface,
      or else are randomly oriented. These arrangements reflect the weak forces acting
      between the DNA molecules themselves, as well as between the molecules and the
      thin film surface.

PMID- 8556447
TI  - Influence of the nature of the reporter gene and selection pressure on stability
      of avian retrovirus vectors.
AB  - We have compared the long-term stability of 2 avian non-replicative retroviral
      vectors in an infected permanent cell line from quail fibroblasts (QT6). Vectors
      NL53 and NPL, expressing both the neo and LacZ genes under control of cis-acting
      elements originated from avian erythroblastosis virus (AEV), are similar to each
      other except for the presence of the phleomycin-resistance SHble gene fused
      upstream the reporter LacZ gene, in NPL vector. The use of such vectors, with an
      uniform backbone, to infect QT6 cells, allowed us to demonstrate that stability
      of the beta-galactosidase activity encoded by the SHble-LacZ fusion gene remains
      higher than that encoded by the native LacZ gene, as determined in the same
      conditions of culture. Moreover, stability of the provirus was dependent on the
      selection pressure. Here we show that stability of beta-galactosidase activity in
      infected QT6 cells was obtained with high dose selection for the selectable SHble
      LacZ fusion gene.

PMID- 8556448
TI  - [Post-embryonic differentiation of a cutaneous electro-receptor].
AB  - In order to decrease the rate of postembryonic development of electroreceptor
      organs, excisions of epidermis and deafferentations were carried out in the
      gymnotid fish Eigenmannia virescens. Twenty-five days later, the epidermis showed
      electroreceptor organs without innervation. Some of these at the beginning of
      their development consisted of masses of identical cells, whereas others showed
      presumed sensory cells whose cytoplasm contained rudimentary synaptic structures.
      The epidermis also showed differentiated tuberous organs with a low number of
      sensory cells. In all these organs, radioactive thymidine was fixed in the nuclei
      of the platform accessory cells. Thirty-five-40 days after surgery, tuberous
      organs were identical to the functional organs, and thymidine was detected in the
      nuclei of the cavity accessory cells. These results show that the gymnotid
      electroreceptor organs can develop before any nervous contact occurs, and suggest
      that they might originate from epidermal cells.

PMID- 8556449
TI  - [Effects of substituted dextran on reinnervation of a skeletal muscle in adult
      rats during regeneration].
AB  - RGTA11 is a chemically substituted dextran that mimics some of the properties of
      heparin or heparan sulphates towards heparin binding growth factors as well as
      inhibits some heparin binding proteases. In vivo RGTA11 has been shown to enhance
      muscle regeneration after crush. We now present evidence that RGTA11 can alos
      favour reinnervation of fast (EDL) as well as slow (soleus) crushed muscles. Both
      types of muscles were injected with RGTA11 after crushing and nerve cutting. In
      EDL muscles, after 16 days, motor end plates were more rapidly reformed and
      choline acetyl-transferase activity was 2 fold higher than in controls. In soleus
      muscles, after 16 days, motor end plates were reformed at normal size while
      controls were on average 30% smaller, the 16S form of acetyl-cholinesterase and
      choline acetyl-transferase activity were twice those of non injected regenerating
      controls. In conclusion, RGTA11 favours axonal growth and synaptic
      differentiation, allowing a more rapid reinnervation and maturation of the
      regenerated fibers. RGTA may present a new family of drugs against neuromuscular
      degenerescence.

PMID- 8556450
TI  - [Micro-morphology of the ovipositor in Hymenoptera and evolution from
      phytophagous Symphyta to parasitoid Apocrita].
AB  - The ovipositor of 1 Symphyta and 12 primitive parasitoid Apocrita belonging of
      the family of Ichneumonidae has been studied with the scanning electron
      microscope (SEM) and for 2 species, semi-thin sections were used. The study shows
      the presence of closed trachea in the 3 pairs of valvulae and a secretory system
      in the 2 pairs of valvulae interlocked into a piercing stylus. We discuss the
      role of trachea and a secretory system leading to excretory pores on the lancets
      of valvulae which occupy very precisely the site of sensory chemoreceptors known
      in more advanced species lacking this secretory system. The micromorphological
      data support the phylogeny within Hymenoptera, from Symphyta to primitive
      parasitoid Apocrita.

PMID- 8556451
TI  - [Free diaminopimelic acid of symbiotic bivalves].
AB  - Free amino acids were analyzed in tissues of symbiotic bivalves from hydrothermal
      vent sites at Galapagos rift, and cold-seeps in Japan trench and Barbados
      subduction area. Diaminopimelic acid (a fragment of the bacterial cell wall
      mureid complex) is, in some cases, one of the most abundant compounds. It's
      presence in the tissues of the bivalves is related to exchanges between host and
      symbionts. Diaminopimelate concentration differences among species may correspond
      to both taxonomic bacterial differences and different carbon translocation
      processes from bacteria to host. Variation among individuals may correspond to
      fluctuation of micro-environmental conditions.

PMID- 8556452
TI  - Cross-reactive immunity against different strains of the hepatitis E virus
      transferable by simian and human sera.
AB  - Monkey infection with the hepatitis E virus induces protection. We confirm the
      humoral nature of this immunity and show that protection is effective against the
      homologous strain, as well as against heterologous strains isolated from Asian
      and African countries. However this immunity is incomplete since only the
      clinical disease seems to be prevented, while the virus is still excreted in
      stools and can even appear in blood as well after serotherapy as previous acute
      or occult infections. We obtained also a preliminary evidence that convalescent
      human sera are also efficient for the passive protection, indicating that
      seroprophylaxis of HEV hepatitis in pregnant women (20% of mortality during the
      3rd trimester of pregnancy) should be attempted in the case of epidemics.

PMID- 8556453
TI  - Hb F-Mauritius [A gamma 23 (B5) Ala deleted]: evidence for an identical hotspot
      for deletions in the various beta-like genes.
AB  - Hemoglobin (Hb) F-Mauritius, a new A gamma chain variant, was identified from a
      dried blood spot collected from a heelprick during neonatal screening for the
      main hemoglobinopathies. This hemoglobin is the first gamma chain variant having
      a one residue deletion: it concerns alanine at position gamma 23. Hb F-Mauritius
      is therefore the counterpart of Hb Freiburg, an unstable variant of the beta
      chain in which the valine residue that occupies position beta 23 is deleted. The
      structural modification of Hb F-Mauritius was characterized by miniaturized
      protein chemistry methods, including sequence determination by mass spectrometry
      measurements. Hb Freiburg was used as a control in several experimental
      procedures. The hypothesis that a similar mechanism for deletion has occurred in
      Hb F-Mauritius and in Hb Freiburg is supported by the high percentage of homology
      observed between the beta and gamma globin genes. In addition, the first exon of
      the beta-globin has been recognized as a hotspot for deletion: several beta
      thalassemic mutations, or abnormal Hbs, with deletions of short nucleotide
      sequences map in this region.

PMID- 8556454
TI  - X-radiation: 100 years of progress in dental diagnosis.

PMID- 8556455
TI  - Radiology and oral and maxillofacial surgery.

PMID- 8556456
TI  - Radiology and oral medicine.

PMID- 8556457
TI  - Radiology and diagnosis.

PMID- 8556458
TI  - Radiology and endodontics.

PMID- 8556459
TI  - Radiology and oral and maxillofacial pathology.

PMID- 8556460
TI  - Early pioneers of oral and maxillofacial radiology.
AB  - Because this year (1995) is the 100th anniversary of the discovery of
      radiography, it is appropriate that we again describe the events surrounding one
      of the most exciting times in our early dental x-ray history--the discovery of
      radiography by Roentgen and the application of radiography to the diagnosis and
      treatment of dental disease. Biographic sketches of some of the more prominent
      early pioneers in oral and maxillofacial radiology are presented, such as those
      of Walkhoff, Morton, Kells, Rollins, and Raper, along with a discussion of their
      contributions to the field.

PMID- 8556461
TI  - History of the American Academy of Oral and Maxillofacial Radiology.
AB  - In celebrating the centennial of the discovery of the x-ray it is fitting to
      relate the history of organized Oral and Maxillofacial Radiology. The American
      Academy of Oral and Maxillofacial Radiology has evolved through four name changes
      and now has expanded its scope to include all modalities of diagnostic imaging.

PMID- 8556462
TI  - Global trends in oral and maxillofacial radiology education.
AB  - Although the content of the undergraduate dental curriculum has evolved alongside
      the changes in dental practice, the methods and structure of the course have
      remained remarkably constant. In this article the recent developments in higher
      education are reviewed in depth and some changes in the pattern and setting of
      oral health outlined. Global trends in education in oral and maxillofacial
      radiology, with particular reference to undergraduate, postgraduate, and
      continuing professional education, are described against this background.

PMID- 8556463
TI  - Current trends in radiographic caries imaging.
AB  - Caries prevalence, lesion site, and lesion behavior have changed over the past
      decade. This review looks at the impact of these changes on radiographic caries
      imaging.

PMID- 8556464
TI  - Diagnostic imaging in dental implantology.
AB  - A success rate for osseointegrated implants approaching 100% has been reported.
      This rate of success has been made possible in part by a comprehensive appraisal
      of the morphologic features of the proposed implantation site: the quality and
      quantity of available bone, the presence of pathoses, the inclination of the
      alveolar process, and the relative location of anatomic structures to the site of
      implantation. Radiography has been found to be invaluable for the assessment of
      the proposed fixture site and for the evaluation of the fixture in time after
      implantation. The question of which radiographic technique to apply, intraoral or
      extraoral, plain film or digital radiography, remains for the clinician to answer
      after careful consideration of all variables.

PMID- 8556465
TI  - Current trends in temporomandibular joint imaging.
AB  - Diagnostic imaging of the temporomandibular joint has undergone a revolutionary
      development during the last two decades. With advanced modalities we have been
      able to differentiate between different articular entities in patients with
      temporomandibular joint disorders. The purpose of this article is to review and
      discuss these modalities and their contribution to our present knowledge, with
      emphasis made on current trends in diagnostic temporomandibular joint imaging.
      The main section deals with diagnostic imaging of the subgroup of disorders with
      internal derangement caused by disk displacement including posttreatment imaging.
      Imaging of pathologic entities characterized by chronic inflammation such as
      rheumatoid arthritis are discussed in the second section. Finally, the potential
      of diagnostic imaging of infrequent conditions such as tumors is briefly
      reviewed. Magnetic resonance imaging has surpassed arthrography and computed
      tomography for the evaluation of most patients in these three subgroups. In
      patients who have various forms of disk displacements with or without
      accompanying bone abnormalities, a diagnostic accuracy of at least 90% may be
      achieved by oblique sagittal and coronal magnetic resonance imaging. In addition,
      alterations in the condylar marrow may be detected. T2-weighted magnetic
      resonance imaging can make a significant diagnostic contribution by demonstrating
      inflammatory reactions such as joint effusion and marrow edema. In the subgroup
      of patients with chronic inflammatory diseases, magnetic resonance imaging may
      also demonstrate abnormalities not shown with other imaging modalities. Disk
      deformation, fragmentation, and destruction may indirectly suggest the presence
      of synovial proliferation/pannus formation, which in selected cases may be
      directly depicted with intravenous gadopentetate dimeglumine. For more detailed
      evaluation of the bone condition and of soft tissue calcifications in joints with
      inflammatory diseases, tumors, or other disorders, computed tomography is the
      preferable imaging modality.

PMID- 8556466
TI  - Computed radiography with photostimulable phosphor in oral and maxillofacial
      radiology.

PMID- 8556467
TI  - Video-based teleradiology for intraosseous lesions. A receiver operating
      characteristic analysis.
AB  - Immediate access to off-site expert diagnostic consultants regarding unusual
      radiographic findings or radiographic quality assurance issues could be a current
      problem for private dental practitioners. Teleradiology, a system for
      transmitting radiographic images, offers a potential solution to this problem.
      Although much research has been done to evaluate feasibility and utilization of
      teleradiology systems in medical imaging, little research on dental applications
      has been performed. In this investigation 47 panoramic films with an equal
      distribution of images with intraosseous jaw lesions and no disease were viewed
      by a panel of observers with teleradiology and conventional viewing methods. The
      teleradiology system consisted of an analog video-based system simulating remote
      radiographic consultation between a general dentist and a dental imaging
      specialist. Conventional viewing consisted of traditional viewbox methods.
      Observers were asked to identify the presence or absence of 24 intraosseous
      lesions and to determine their locations. No statistically significant
      differences in modalities or observers were identified between methods at the
      0.05 level. The results indicate that viewing intraosseous lesions of video-based
      panoramic images is equal to conventional light box viewing.

PMID- 8556468
TI  - Computerized three-dimensional magnetic resonance imaging reconstructions of
      temporomandibular joints for both a model and patients with temporomandibular
      pain dysfunction.
AB  - The aim of this study was to assess computerized three-dimensional reconstruction
      of magnetic resonance images generated of a temporomandibular joint model and the
      temporomandibular joints of five patients with varying degrees of
      temporomandibular joint pain and dysfunction. The three-dimensional image
      reconstruction of an artificial temporomandibular joint model, consisting of a
      human dried skull and synthetic disk, was used to test the accuracy and
      reproducibility of the three-dimensional technique. It was found that
      computerized three-dimensional reconstruction improved the display format of
      magnetic resonance imaging by enabling multiple two-dimensional images in shades
      of grey to be viewed as one three-dimensional image with anatomic structures
      colored as desired. Further, by rotating this image, the anatomic relationships
      of the temporomandibular joint could be seen from any viewpoint. Volume
      measurements showed accuracy and reproducibility by independent operators.
      Computerized three-dimensional reconstruction was applied to the magnetic
      resonance images obtained from patients. They were used to assess magnetic
      resonance imaging technique and its applications for interpreting the clinical
      findings. Disk position, as revealed by the three-dimensional images, was found
      to correspond with the clinical assessment, except in two instances when the
      original, right-sided, magnetic resonance imaging was unclear. Three-dimensional
      reconstruction was simple to apply, required no patient involvement, and made
      multiple magnetic resonance images easier to interpret.

PMID- 8556469
TI  - Oral signs as indicators of possible osteoporosis in elderly women.
AB  - The relationship between oral signs and osteoporosis was investigated to assess
      the possibility of using this as an indicator of postmenopausal osteoporosis.
      Sixty-four women between the ages of 50 and 70 years were evaluated. Osteoporotic
      signs consisted of thoracic spine fracture as demonstrated on lateral chest
      radiographs. Oral signs were the number of teeth present, mandibular cortical
      width, alveolar bone resorption, and the morphologic classification of the
      inferior cortex on panoramic radiographs. The number of teeth present (N) was
      highly related to the probability of thoracic spine fracture and was used to
      derive the probability equation for the presence of thoracic spine fracture:
      probability value = 1/(1 + e-z), Z = 18.68-0.29 age -0.27N. A probability value
      higher than 0.5 suggests the possibility of thoracic spine fracture. It was
      concluded that this equation could serve as a simple and useful tool for dentists
      to assess the possibility of latent osteoporosis.

PMID- 8556470
TI  - Will immunogenicity limit the use, efficacy, and future development of
      therapeutic monoclonal antibodies?
AB  - While monoclonal antibodies show promise for use in the treatment of a variety of
      disease states, including cancer, autoimmune disease, and allograft rejection,
      generation of anti-antibody responses still remains a problem. For example, 50%
      of the patients who receive OKT3 produce blocking antibodies that interfere with
      its binding to T cells, thus decreasing the therapeutic effect (51). HAMA
      responses have also interfered with tumor imaging (39,40) and radioimmunotherapy
      (56). The generation of an anti-antibody response is dependent on many factors.
      These include the dose of antibody, the number of injections of antibody, the
      immunogenicity of the antibody, the form of the antibody, and the
      immunocompetence of the recipient. Predictably, both the number of injections of
      antibody and the dosage are influential in the generation of an anti-antibody
      response. It is apparent that human antibodies, chimeric antibodies, and mouse
      Fab fragments are much less likely to induce anti-antibody responses than intact
      mouse monoclonal antibodies or mouse F(ab')2 fragments when one injection is
      administered. Injections of human or chimeric antibodies appears to reduce
      immunogenicity, but the probability that anti-antibody responses can still be
      induced on multiple injections must be considered and appropriately evaluated.
      Several areas demand extensive investigation to enhance the clinical utility of
      monoclonal antibodies. First, results of thorough clinical trials with human or
      chimeric antibodies need to be evaluated for the induction of anti-antibodies
      after multiple injections of antibodies. Second, less immunogenic forms of
      antibodies (Fab, Fv) need to be studied for their clinical efficacies and for
      their abilities to induce anti-antibody responses.

PMID- 8556471
TI  - Sustained cellular immune responses to Borrelia burgdorferi: lack of correlation
      with clinical presentation and serology.
AB  - Fifty-one patients with erythema migrans were followed up prospectively with
      serial clinical evaluations, serologic determinations for antiborrelial
      antibodies, and lymphocyte stimulation responses to Borrelia burgdorferi antigens
      to determine (i) the factors associated with sustained cellular immune responses
      and (ii) whether lymphocyte stimulation is a good indicator of prior exposure to
      B. burgdorferi in patients treated early after erythema migrans. Positive
      lymphocyte stimulation responses ( > 2 standard deviations above normal control
      values) were found in 15 (29%) of 51 patients 3 months after treatment for
      erythema migrans and in 8 (18%) of 44 patients 1 year posttreatment. Heightened
      lymphocyte responses were not associated with the number or duration of erythema
      migrans lesions prior to treatment, the mean size of the largest erythema migrans
      lesion, or the number of symptoms at the time of presentation. The development of
      Jarisch-Herxheimer reaction, choice of antibiotic, and clinical outcome also were
      not associated with a positive lymphoproliferation assay result. Changes in the
      lymphocyte stimulation indices between the two time points assessed (3 months and
      1 year posttreatment) also did not correlate with the above variables. When
      serologic results and lymphoproliferative responses were evaluated as categorical
      or continuous variables, there were no correlations between values. One year
      after treatment for early Lyme disease, lymphocyte reactivity is not a good
      indicator of prior infection with B. burgdorferi.

PMID- 8556472
TI  - Acute monocytic leukemia in a dog with X-linked severe combined immunodeficiency.
AB  - We describe the occurrence of acute monocytic leukemia in a dog with X-linked
      severe combined immunodeficiency (XSCID) that had been raised in a gnotobiotic
      environment for 20 months. This case represents the first reported instance of
      malignancy in canine XSCID, the first case of acute monocytic leukemia in any
      species with severe combined immunodeficiency, and the first documented
      malignancy in any species with XSCID that was not associated with immunotherapy.

PMID- 8556473
TI  - Presence of Leishmania braziliensis in blood samples from cured patients or at
      different stages of immunotherapy.
AB  - By using a PCR assay specific for Leishmania braziliensis in blood samples, we
      detected this parasite in patients cured by immunotherapy or at different stages
      of treatment. We also found the parasite in subjects who had never suffered
      leishmaniasis but who had lived in endemic areas and migrated to nonendemic ones
      many years ago. These results suggest that L. braziliensis infections are
      difficult to eradicate and that a clinical cure but rarely a complete elimination
      of the parasite is generally accomplished.

PMID- 8556474
TI  - Effects of histoplasmin M antigen chemical and enzymatic deglycosylation on cross
      reactivity in the enzyme-linked immunoelectrotransfer blot method.
AB  - The enzyme-linked immunoelectrotransfer blot (EITB) method was evaluated as a
      suitable method for detecting antibodies against M antigen of Histoplasma
      capsulatum by use of both glycosylated and deglycosylated M protein of
      histoplasmin (HMIN). Sera from patients with histoplasmosis,
      paracoccidioidomycosis, blastomycosis, coccidioidomycosis, and aspergillosis were
      tested by the EITB with glycosylated M protein of HMIN. This assay demonstrated
      100% sensitivity with histoplasmosis serum samples, all of which reacted with the
      94-kDa glycoprotein (M antigen). Although the EITB is highly sensitive, it is not
      specific for histoplasmosis when glycosylated M protein is used as an antigen. A
      total of 81% of paracoccidioidomycosis, 25% of blastomycosis, 33% of
      coccidioidomycosis, 73% of aspergillosis, and 16% of tuberculosis serum samples
      cross-reacted with M protein of HMIN and yielded patterns indistinguishable from
      those obtained with histoplasmosis serum samples. The EITB reactions with both
      untreated M antigen and M antigen altered by periodate oxidation or by
      deglycosylation with endoglycosidases were compared. Cross-reactions with
      heterologous sera in the EITB could be attributed to periodate-sensitive
      carbohydrate epitopes, as reflected by the increase in the test specificity from
      46.1 to 91.2% after periodate treatment of M protein. The EITB for the detection
      of antibodies to M antigen is a potential diagnostic test for histoplasmosis,
      provided that periodate-treated M protein is used as an antigen.

PMID- 8556475
TI  - Quantitative flow cytometric analysis of opsonophagocytosis and killing of
      nonencapsulated Haemophilus influenzae by human polymorphonuclear leukocytes.
AB  - Since nonencapsulated Haemophilus influenzae persists in the lower respiratory
      tracts of patients with chronic bronchitis despite the presence of specific
      antibodies, complement, and polymorphonuclear leukocytes (PMNs),
      opsonophagocytosis of H. influenzae was analyzed. Nonencapsulated H. influenzae
      isolated from the sputa of chronic bronchitis patients was labeled with
      fluorescein isothiocyanate and incubated with human PMNs in the presence of
      complement and antibodies for 30 min at 37 degrees C. Candida albicans was added
      to each sample as an internal standard, and the reduction of the number of
      bacteria was determined by flow cytometry. Fluorescence quenching with ethidium
      bromide was used to discriminate between intracellular and extracellular
      bacteria. Opsonophagocytosis of viable H. influenzae d1 was 17% +/- 29% in the
      presence of complement and human pooled sera containing high titers of strain
      specific antibodies. Opsonophagocytosis of six other H. influenzae strains was
      also poor. Under the same conditions, opsonophagocytosis of Staphylococcus aureus
      was 90% +/- 5%, and opsonophagocytosis of C. albicans was 55% +/- 23%. About half
      of the number of H. influenzae bacteria associated with PMNs was internalized.
      Opsonophagocytosis of heat-killed H. influenzae d1 (41% +/- 20%) was higher than
      that of viable bacteria of the same strain (P < 0.05). This result suggests that
      the accessibility of epitopes on H. influenzae for opsonizing antibodies is
      better on killed than on viable bacteria. We conclude that viable nonencapsulated
      H. influenzae is poorly opsonophagocytized in the presence of strain-specific
      antibodies and complement.

PMID- 8556476
TI  - The Vitek immunodiagnostic assay for detection of immunoglobulin M toxoplasma
      antibodies.
AB  - We compared the Vitek immunodiagnostic assay for detection of immunoglobulin M
      (IgM) toxoplasma antibodies (VIDAS TXM) with an IgM enzyme-linked immunosorbent
      assay (ELISA) which we developed. A total of 407 serum samples from 391 adults
      were used for this study. We also examined 17 serial serum samples from four
      women who had seroconverted during gestation. We observed a sensitivity of 99.5%,
      a specificity of 93%, a positive predictive value of 93.6%, a negative predictive
      value of 99.5%, and a global agreement of 96.3%. In each case of seroconversion
      the VIDAS TXM became positive at the same time as did the IgM ELISA.

PMID- 8556477
TI  - Purification of Borrelia burgdorferi outer surface protein A (OspA) and analysis
      of antibody binding domains.
AB  - The major outer surface protein, OspA, of Borrelia burgdorferi is a lipoprotein
      which is a particular interest because of its potential as a vaccine candidate.
      However, serotypic and genetic analysis of OspA from both European and North
      American strains have demonstrated antigenic and structural heterogeneities. We
      purified OspA to homogeneity by exploiting its resistance to trypsin digestion.
      By treating spirochetes with trypsin and then using Triton X-114 extraction and
      ion-exchange chromatography, we obtained a yield of 2 mg of pure OspA protein per
      liter of culture. INtrinsic labeling with [14C]palmitic acid confirmed that OspA
      was lipidated, and partial digestion established lipidation at the amino-terminal
      end of the molecule. The reactivity of five anti-OspA murine monoclonal
      antibodies to nine different isolates of B. burgdorferi was ascertained by
      Western blot (immunoblot) analysis. Purified OspA was fragmented by enzymatic or
      chemical cleavage, and the monoclonal antibodies were able to define four
      distinct immunogenic domains. Further resolution of the epitope specificity to
      determine humoral and cellular immune responses to OspA has implications for
      vaccine development and for the utility of this protein as a reagent in
      diagnostic testing for Lyme borreliosis.

PMID- 8556478
TI  - Markers of hepatitis C and B virus infections among blood donors in Ho Chi Minh
      City and Hanoi, Vietnam.
AB  - Blood donors in two cities in Vietnam were tested for markers of hepatitis C
      virus (HCV) and hepatitis B virus infections. Antibody to HCV was detected by
      passive hemagglutination with antigens of the second generation in 101 (20.6%) of
      491 donors in Ho Chi Minh City; it was detected less frequently (P < 0.001) in
      donors in hanoi (4 [0.8%] of 499). HCV RNA was tested for in donors with antibody
      by PCR with nested primers from the 5'-noncoding region and detected in 79 donors
      in Ho Chi Minh City and 4 donors in Hanoi. HCV RNA was genotyped by PCR with type
      specific primers from the core gene. Of 83 HCV carriers from Vietnam, 24 (29%)
      were infected with HCV of genotype I/1a 19 (23%) were infected with II/1b, 4 (5%)
      were infected with III/2a, and 2 (2%) were infected with mixed genotypes (I/1a
      and II/1b); HCV genotypes in the remaining 34 (41%) donors, including all 4
      donors in Hanoi, were not classifiable into I/1a, II/2a, IV/2b, or V/3a. Of the
      10 isolates with unclassifiable genotypes, 2 showed substantial sequence
      divergence within the 5'-noncoding region from reported isolates with known
      genotypes (I/1a to 6a). An analysis of part of the core gene sequence indicated
      that six of the remaining isolates most likely represented new HCV genotypes.
      Hepatitis B surface antigen and the corresponding antibody, respectively, were
      detected in 15 (3.1%) and 234 (47.7%) donors in Ho Chi Minh City as well as 15
      (3.0%) and 248 (49.7%) donors in Hanoi. These results indicate an extensive
      spread of HCV among Ho Chi Minh City donors and HCV of novel genotypes in
      vietnam.

PMID- 8556479
TI  - Substance P augments tumor necrosis factor release in human monocyte-derived
      macrophages.
AB  - Substance P (SP) is an undecapeptide that has the amino sequence Arg-Pro-Lys-Pro
      Gin-Gln-Phe-Phe-Gly-Leu-Met-NH2 and that belongs to a family of structurally
      related peptides known as tachykinins, the latter are widely distributed in the
      central nervous system. SP is involved in the biological activities of cells in
      the immune system, including the induction of cytokines in immune cells. We have
      investigated the effects of SP on constitutive and/or lipopolysaccharide (LPS)
      induced expression of tumor necrosis factor (TNF) in cultured blood monocyte
      derived macrophages (MDM). Cells cultured in vitro for 14 days were treated with
      SP at various concentrations (10(-10) to 10(-6M) in the presence of LPS before
      culture supernatants were harvested. TNF bioactivity in culture supernatants was
      measured with L929 cell line MDM from 10 of 12 donors treated with a SP alone
      showed increased TNF production. SP and LPS also interacted in a synergistic
      fashion in upregulating TNF production in MDM from responders. The stimulatory
      effect of SP was inhibited by two SP antagonists, spantide ([D-Arg-1-D-Trp-7-D
      Trp-7-D-Trp-9-leu-11]-SP) and CP-96,345 (a nonpeptide antagonist of the SP
      receptor). In addition, an anti SP polyclonal antibody blocked the SP effect on
      TNF production in cultured MDM, further indicating the specificity of these
      effects. These results demonstrate that SP is an important regulator of monokine
      production by human monocytes/macrophages.

PMID- 8556480
TI  - Differential effects of interleukin-2 and interleukin-4 on immunomodulatory role
      of platelet-activating factor in human B cells.
AB  - Platelet-activating factor (PAF), a naturally occurring phospholipid cytokine, is
      a potent mediator of allergic and inflammatory reactions, as well as a modulator
      of immune responses. In the present study we showed that PAF is involved in early
      B-cell activation, as demonstrated by the increased cyclic AMP (cAMP) generation
      by PAF in a time- and dose-dependent manner in anti-mu antibody- plus B-cell
      growth factor-activated normal human peripheral blood B lymphocytes. PAF also
      regulated differentiation by causing a biphasic response on immunoglobulin M
      (IgM) production with an inhibitory signal generated at 10(-6) M and a
      stimulatory signal generated at 10(-8) to 10(-10) M. PAF enhanced IgA secretion.
      The regulation exerted by PAF was shown to be specific because the addition of
      the PAR antagonist CV-3988 abrogated these effects and the inactive form of PAF,
      lyso-PAF, induced neither cAMP generation nor immunoglobulin secretion in normal
      human B cells. Other cytokines, interleukin-2 (IL-2) and IL-4, potent mediators
      of the immune response, were unable to elicit a cAMP response in B cells.
      However, the addition of PAF (10(-6) M) with wither IL-2 or IL-4 enhanced cAMP
      production above the levels enhanced by the addition of PAF alone. IL-2 or IL-4,
      individually, stimulated IgM production, yet costimulation with PAF resulted in a
      differential effect between IL-2 and IL-4. PAF down-regulated the IL-4-induced
      IgM secretion, whereas the IL-2-induced IgM secretion was enhanced. The presence
      of CV-3988 returned all valued to those obtained with IL-2 or IL-4 alone,
      demonstrating the specificity of PAF. These data suggest that PAF is an important
      B-cell immunomodulator which can interact with other leukocyte cell mediators.

PMID- 8556481
TI  - Serum cytokine levels in patients with Alzheimer's disease.
AB  - Alzheimer's disease (AD) has been proposed to be an inflammatory disorder. In a
      recent study, markedly elevated levels of the anti-inflammatory cytokine
      transforming growth factor beta (TGF-beta) in the serum and cerebrospinal fluid
      of patients with advanced AD suggested a potential predictive value of this
      cytokine in patients with AD. In the present prospective study, we tested the
      hypothesis that the levels of TGF-beta in serum would be increased in patients
      with AD and could thereby serve as a diagnostic marker. We found that serum TGF
      beta levels but not proinflammatory cytokine levels were significantly (P < 0.05)
      elevated in patients with AD (n = 22) in comparison with the levels in their
      healthy spousal controls. Also, serum TGF-beta levels were positively correlated
      (r = 0.45; P < 0.05) with disease severity. Nevertheless, the elevation in serum
      TGF-beta levels in patients with Ad was modest, and considerable overlap with the
      control values suggests that the diagnostic usefulness of this cytokine for AD is
      limited.

PMID- 8556482
TI  - Do high levels of C-reactive protein in Tanzanian children indicate malaria
      morbidity.
AB  - Children under 6 years of age living in an area of Tanzania highly endemic for
      malaria were tested for C-reactive protein (CRP) in order to determine how the
      acute-phase response is related to malaria in children of different ages and to
      investigate whether serum CRP concentrations might be useful in the qualification
      of morbidity in such children. The median CRP level in the 629 finger-prick blood
      samples measured, 6.0 mg/liter, was much higher than that reported in the blood
      of children in Europe. The CRP concentration was correlated with recent illness
      reported by the parents. High CRP levels were most strongly associated with
      Plasmodium falciparum parasitemia in children under 1 year of age. In older
      children, lower levels of CRP were associated with parasitemia, and fewer
      children had increased CRP levels attributable to parasitemia. The levels of
      malaria-attributable CRP appear to track the acquisition of parasitological and
      clinical tolerance in this area with very high levels of P. falciparum
      transmission. Determination of CRP levels should be useful in the rapid
      assessment of the overall burden of morbidity, especially in infants. In areas
      where malaria is endemic, CRP associated with increased parasite densities
      provides an objective measure of malaria-specific morbidity. This would be an
      efficient approach to estimating malaria morbidity risks from small-scale
      serological surveys.

PMID- 8556483
TI  - Antineurofilament and antiretinal antibodies in AIDS patients with
      cytomegalovirus retinitis.
AB  - Sera obtained from AIDS patients with cytomegalovirus (CMV) retinitis before and
      after treatment with foscarnet, AIDS patients with human immunodeficiency virus
      (HIV) retinopathy, AIDS patients without retinal disease, and normal healthy
      controls with and without positive CMV serologies were assayed for the presence
      of antibodies against the 200-kDa outer, 160-kDa middle, and 68-kDa core subunits
      of the neurofilament triplet. Additional studies were performed to determine the
      presence of antibodies reactive with proteins extracted from crude human retinal
      antigen preparations. Antibodies against the 200-, 260-, and 68-kDa proteins of
      the neurofilament triplet were detected in 15 of 15 AIDS patients with CMV
      retinitis. The expression of these antibodies was unaffected, qualitatively, by
      successful treatment with foscarnet. In contrast, only 30% of patients with HIV
      retinopathy unrelated to CMV, fewer than 35% of AIDS patients with positive CMV
      titers but without evident retinitis, and fewer than 25% of healthy controls with
      positive or negative CMV titers possessed antibodies against any of the triplet
      proteins (P < 0.001). Antibodies against several clusters of retinal antigens
      were also identified in the sera of patients with CMV retinitis. In summary, the
      data indicate that retinal elements damaged by CMV infection induce an antibody
      response against the 200-, 160-, and 68kDa components of the neurofilament
      triplet as well as other, as yet undefined retinal antigens.

PMID- 8556484
TI  - Evaluation of an animal model system for cryptosporidiosis: therapeutic efficacy
      of paromomycin and hyperimmune bovine colostrum-immunoglobulin.
AB  - Several immunodeficient rodent models currently exist in which persistent,
      largely asymptomatic, Cryptosporidium parvum infections can be established.
      Piglets, in contrast, develop a self-limiting diarrheal illness. We have
      consequently developed an animal model system in which scid mice were used to
      screen drugs for inhibitory activity against C. parvum, after which the drugs'
      therapeutic potential was evaluated with piglets. Paromomycin and hyperimmune
      bovine colostrum-immunoglobulin were selected to evaluate this system. C. paravum
      infections in suckling scid mice tended to be associated with villus surfaces,
      while in weaned and in older scid mice infections were more commonly localized in
      abscessed crypts. Rates of oocyst shedding in suckling scid mice were 50 to 200
      times higher than in weaned mice and therefore made suckling mice a considerably
      more sensitive model for drug testing. Paromomycin given in high doses over 9 to
      10 days was not toxic to either scid mice (3,000 mg/kg of body weight per day) or
      piglets (500 mg/kg/day). Paromomycin treatment was very effective against villus
      surface infections in suckling mice and considerably less effective against
      infections in inaccessible sites such as abscessed crypts and stomach pits seen
      in weaned and adult scid mice. The therapeutic efficacy of paromomycin in piglets
      depended on the severity of the diarrheal illness. Mild to moderate diarrhea and
      infection were cleared after paromomycin treatment of piglets infected with one
      C. parvum isolate. However, paromomycin had no impact on severely affected
      piglets infected with a second isolate, presumably because of a rapid transit
      time through the gut. In contrast to paromomycin hyperimmune bovine colostrum
      immunoglobulin treatment reduced the rate of C. parvum infection moderately in
      scid mice and only slightly in piglets, again probably because of a rapid transit
      time through the gut and inactivation in the stomach. It was also clear that the
      impact of effective drugs against C. parvum can be detected within 5 days after
      the onset of treatment in either model.

PMID- 8556485
TI  - Maternal antibodies and acquired serological response to Moraxella catarrhalis in
      children determined by an enzyme-linked immunosorbent assay.
AB  - An enzyme-linked immunosorbent assay (ELISA) for determination of serum
      immunoglobulin G (IgG) antibodies to Moraxella catarrhalis was developed, with an
      ultrasonic extract of M. catarrhalis immobilized on polystyrene microtiter plates
      serving as the antigen. The specificity was determined by adsorption tests. All
      of the 541 women tested showed a high level of maternal IgG antibodies to M.
      catarrhalis in umbilical cord blood specimens. One hundred eighty-nine children
      aged 0 to 15 years were examined. A low level of IgG antibodies to M. catarrhalis
      in serum was found in children aged up to 1 year; in older children, the levels
      increased with age. Levels in the same range as maternal IgG antibody levels were
      reached at the age of 10 years. The level of antibodies in children did not
      correlate with the state of colonization with M. catarrhalis or with the state of
      acute lower respiratory tract infection. Pairs of acute-phase and convalescent
      phase serum samples did not discriminate between the children with M. catarrhalis
      in pure culture and those with mixed cultures of M. catarrhalis, Haemophilus
      influenzae, and Streptococcus pneumoniae. In adult women, high IgG antibody
      levels and low colonization rates with M. catarrhalis were found, whereas in
      small children, low IgG antibody levels and high colonization rates were found.

PMID- 8556486
TI  - Respiratory syncytial virus group-specific antibody response in nasopharyngeal
      secretions from infants and children after primary infection.
AB  - Respiratory syncytial virus (RSV) group-specific immunoglobulin A (IgA) and IgG
      enzyme-linked immunosorbent assay antibody and neutralizing antibody responses
      were determined for nasopharyngeal secretions (NPS) from 27 infants and children
      (6 to 18 months of age) undergoing primary infection with RSV group A or B
      strain. IgA and IgG antibody responses against RSV envelope glycoproteins (fusion
      [F] and large [G] glycoprotein) in NPS were also analyzed. Most subjects examined
      developed moderate levels of NPS IgA and IgG antibodies and neutralizing antibody
      activity to both group A and B strains in convalescent phase; however, the levels
      of antibodies to homologous strains were significantly higher than to the
      heterologous strains. Patients infected with group A developed antibodies in both
      F and G glycoproteins of A2 strains (group A). Patients infected with group B
      developed levels of antibody activity to F glycoprotein of A2 strain similar to
      those of patients infected with group A. However, these subjects developed little
      or no antibody response to G glycoprotein of A2 strain. These data suggest that
      the IgA and IgG antibody responses to G glycoprotein in the respiratory tract are
      group specific. It is suggested that lack of antibody response to the G
      glycoprotein of the heterologous group in the respiratory tract may determine the
      outcome of reinfection with other RSV strains.

PMID- 8556487
TI  - Production of antisera against the enterotoxin of Bacteroides fragilis and their
      use in a cytotoxicity neutralization assay of HT-29 cells.
AB  - To study the enterotoxin of Bacteroides fragilis, the colon carcinoma cell line
      HT-29 was used in a standard cytotoxicity assay. We produced high-titer
      neutralizing antisera in rabbits and goats against both crude and purified toxin
      and developed a cytotoxicity neutralization assay for use in confirming
      enterotoxin activity in culture filtrates and stools. The neutralization titers
      of the antisera on the colon carcinoma cell line HT-29 ranged from 1,600 to
      2,400. In an antibody screening enzyme-linked immunosorbent assay, titers ranged
      from 10(4) to 10(5). The antisera produced against the highly purified toxin also
      neutralized the enterotoxic activity of the toxin and were monospecific by
      immunoelectrophoresis.

PMID- 8556488
TI  - Evaluation of a Treponema pallidum enzyme immunoassay as a screening test for
      syphilis.
AB  - The CAPTIA Syphilis-G enzyme immunoassay for the detection of antibodies to
      Treponema pallidum was evaluated as a screening test for syphilis in comparison
      with the standard rapid plasma reagin (RPR) test. One thousand samples were
      tested, and the standard fluorescent treponemal antibody absorption test and the
      standard microhemmaglutination test were used to confirm the presence of
      treponemal antibodies. Diagnosis of syphilis was based on traditional standard
      serology results. Clinical data used in the diagnosis of patients whose samples
      yielded conflicting results were provided by physicians. Initially, 7 patients
      whose samples were reactive in the RPR test and 14 patients whose samples yielded
      positive or equivocal results in the CAPTIA Syphilis-G test were diagnosed as not
      being infected. After discrepancies due to technical problems were reconciled,
      samples from six patients remained reactive in the RPR test and that from one
      patient remained positive in the CAPTIA Syphilis-G test. In addition, seven
      patients whose samples were nonreactive in the RPR test and two patients whose
      samples were negative in the CAPTIA Syphilis-G test were diagnosed as having
      untreated syphilis. After discrepancies were reconciled, samples from five
      patients remained nonreactive in the RPR test and none remained negative in the
      CAPTIA Syphilis-G test. Final results indicate that the specificities are 99.4
      and 99.9%, respectively. In addition to the improved sensitivity and specificity
      of the CAPTIA Syphilis-G screen, other potential benefits of this assay lead us
      to believe that this method could serve as a better screening tool than the RPR
      test.

PMID- 8556489
TI  - Inhibitory effect of 3'-azido-3'-deoxythymidine on proliferative responsiveness
      of CD8+ lymphocytes to interleukin-2.
AB  - Although several studies have shown that 3'-azido-3'-deoxythymidine (AZT) is not
      toxic for CD4+ lymphocytes, its effect on CD8+ cells has never been studied in a
      systematic way. We purified CD8+ cells from the peripheral blood mononuclear
      cells of both human immunodeficiency virus (HIV)-seronegative and HIV-infected
      individuals by means of magnetic beads that had been coated with monoclonal
      antibodies. We report that AZT, but not two other nucleosides tested, inhibited
      the interleukin-2-dependent proliferation of CD8+ lymphocytes in a dose-dependent
      manner. No such effect was observed with regard to CD4(+)-enriched populations.
      The AZT-mediated antiproliferative effect did not appear to be related to either
      the CD4+ count or to prior treatment with this drug in the case of HIV
      seropositive subjects.

PMID- 8556490
TI  - Analysis of human antiviral cytotoxic T-lymphocyte responses for vaccine trials
      using cryopreserved mononuclear leukocytes: demonstration of feasibility with
      influenza virus-specific responses.
AB  - The feasibility of measuring virus-specific human cytotoxic T-lymphocyte (CTL)
      activity by using cryopreserved mononuclear leukocytes to support clinical
      vaccine trials was addressed. Autologous fresh and cryopreserved cells from the
      same sample of peripheral blood were used as sources of CTL precursors and were
      tested for influenza virus-specific activity. The data indicated that virus
      specific CTL activity could be measured by using cryopreserved cells; this could
      also be done in assays that are designed to characterize the responsible effector
      cell population.

PMID- 8556491
TI  - Identification of antigens of pathogenic free-living amoebae by protein
      immunoblotting with rabbit immune and human sera.
AB  - Prominent antigens of pathogenic and nonpathogenic free-living amoebae were
      identified by using polyclonal rabbit immune sera in immunoblot assays. The
      intent was to determine if prominent epitopes identified with rabbit immune sera
      could also be recognized by human sera. With rabbit sera, the development of
      immunoreactive bands was restricted to molecular masses of greater than 18.5 kDa
      for Naegleria, Hartmannella, and Vahlkampfia antigens. Two or more broad bands of
      less than 18.5 kDa were prominent features in three different Acanthamoeba
      species. Few cross-reactive antibodies could be detected between representative
      species of the three different subgroups of Acanthamoeba. Naegleria antigen was
      likewise serologically distinct, as were Hartmannella and Vahlkampfia antigens.
      The relative lack of cross-reacting antibodies between the pathogenic amoebae
      suggested that i would be desirable to use a panel of amoebic antigens to
      represent the range of serologically distinct antigens for assessing reactive
      antibodies in human sera. In pooled human sera (10 serum specimens per pool), the
      appearance of minimally reactive bands ranging from 32.5 to 106 kDa was a common
      feature of all six antigens. A prominent band of less than 18.5 kDa was
      identified in the Acanthamoeba culbertsoni antigen lane in 2 of the 10 human
      serum specimen pools. When sera from each of the two groups were tested
      individually by immunoblotting, the reaction with A. culbertsoni antigen could be
      associated with one individual. By using a panel of amoebic antigens, this method
      could prove useful in recognizing undiagnosed amoebic infections by revealing
      specific reactive antibodies.

PMID- 8556492
TI  - Epitope-specific antibody response against glycoprotein E of pseudorabies virus.
AB  - In this study we investigated the epitope-specific antibody response against
      glycoprotein E (gE) of pseudorabies virus. Epitope-specific antibody responses
      were investigated by enzyme-linked immunoperoxidase monolayer assays. In a
      vaccinated crossbred pig population, most pigs responded to antigenic domain E
      and to a lesser degree to antigenic domains C and D. Only few pigs responded to
      antigenic domains F, A, and B. Using vaccinated pigs, we investigated the
      influence of two different pseudorabies virus strains and the genetic background
      of the host on the epitope-specific antibody response. More pigs infected with
      the virulent NIA-3 strain had a detectable antibody response against antigenic
      domains C, F and A than did pigs infected with the mildly virulent Sterksel
      strain (P < or = 0.05; Fisher's exact test). No differences in the epitope
      specific antibody responses of two genetically different pig breeding lines were
      observed (P > or = 0.1; Fisher's exact test). In both breeding lines the
      incidence of the epitope-specific antibody response was comparable to that in the
      crossbred pig population. In addition, we studied the epitope-specific antibody
      responses were strikingly different and indicated that genetic background
      influenced the epitope-specific antibody response. Of the serum samples of mice
      with C57BL and a BALB background, 40 and 17% respectively, were positive in the
      one of the epitope-specific immunoassays. In contrast to pigs, mice responded
      predominantly to antigenic domain D and to a lesser degree to antigenic domains E
      and B. Only few mice had a detectable antibody response against antigenic domains
      C and A, and none had a detectable antibody response against antigenic domain F.

PMID- 8556493
TI  - Cattle serologically positive for Brucella abortus have antibodies to B. abortus
      Cu-Zn superoxide dismutase.
AB  - In this study, we demonstrated by a Cu-Zn superoxide dismutase-specific enzyme
      linked immunoassay that cattle that are serologically positive for Brucella
      abortus have serum immunoglobulin G antibodies to B. abortus Cu-Zn superoxide
      dismutase. The specificity of the antibody reactivity was confirmed by Western
      blot (immunoblot) analysis with B. abortus salt-extractable proteins containing
      native Cu-Zn superoxide dismutase and with recombinant B. abortus Cu-Zn
      superoxide dismutase. The results represent a first step in the direction of the
      development of a multiprotein diagnostic reagent for bovine brucellosis.

PMID- 8556494
TI  - Comparison of corticosteroid- and L3T4+ antibody-immunosuppressed mouse models of
      Pneumocystis carinii pneumonia for evaluation of drugs and leukocytes.
AB  - An immunologically immunosuppressed mouse model of Pneumocystis carinii pneumonia
      using antibody developed by Dialynas et al. (Immunol. Rev. 74:29-55, 1983)
      directed to L3T4+ T cells (referred to as L3T4+ antibody) was compared with a
      corticosteroid-immunosuppressed mouse model. Corticosteroid- or L3T4+ antibody
      immunosuppressed BALB/c mice transtracheally inoculated with P. carinii developed
      severe infections within 5 weeks after inoculation and responded to treatments
      with an echinocandin B analog, LY302146, or trimethoprim plus sulfamethoxazole so
      that they had decreased numbers of P. carinii cysts and trophozoites. LY302146
      appeared to be more effective in L3T4+ antibody-immunosuppressed mice than in
      dexamethasone-immunosuppressed mice. Leukocyte populations in lungs of both mouse
      models during development of infection and during treatment were compared by
      using immune cell-specific staining. Lungs of L3T4+ antibody-immunosuppressed
      mice had many more cells detected with pan-B antibody and pan-T antibody than
      dexamethasone-immunosuppressed mice and the lungs of successfully treated mice
      had about the same numbers of macrophages as those of nonimmunosuppressed
      uninfected mice. The immunologically immunosuppressed model will allow study of
      cytokines and other immune modulators alone and in combination with drugs.

PMID- 8556495
TI  - Monokine-mediated increase in human immunodeficiency virus type 1 expression in
      chronically infected promonocyte- and T-cell-derived lines.
AB  - The ACH-2 cell clone derived from a human T-cell line and chronically infected
      with human immunodeficiency virus 1 (HIV-1) and the U1 cell clone derived from a
      human promonocyte cell line and also chronically infected with HIV-1 produce HIV
      1 in a response to stimulation with monokine-enriched supernatants prepared from
      highly purified populations of peripheral blood-derived human monocytes. Monokine
      mediated expression of HIV-1 in these cell lines resulted in augmented virus
      production reflected by increases in reverse transcriptase (RT) activity,
      production of p24 antigen, and synthesis of major viral proteins. Examination of
      the cells by electron microscopy revealed numerous HIV-1 virions in the cells
      treated with the supernatants. This stimulation of virus production by monokine
      enriched supernatants resulted in approximately 100-fold increases in RT activity
      and p24 antigen expression in comparison with those in untreated U1 and ACH-2
      cells. Absorption of monokine-enriched supernatants with rabbit anti-tumor
      necrosis factor alpha antibody removed most, but not all, of the induced HIV-1 RT
      activity and p24 antigen expression in U1 and ACH-2 cell lines, suggesting that
      tumor necrosis factor alpha in the monokine-enriched supernatants is a major
      factor in the induction of HIV-1 expression in these cells.

PMID- 8556496
TI  - Measurement of pneumococcal capsular polysaccharide serotype-specific
      immunoglobulin G in human serum, a method for assigning weight-based units to
      proposed reference sera.
AB  - A direct method for measuring serotype-specific, class-specific antibody in
      proposed human reference sera is described. The assay uses a 125I-labeled,
      isotopically pure immunoglobulin G (IgG) as a primary standard in an antigen
      antibody solid-phase enzyme immunoassay. From the measurement of specific
      radioactivity bound to the absorbed antigen, serotype-specific IgG concentrations
      and optical density values can be directly related to optical density and
      serotype-specific IgG values for the reference serum. We used this method to
      provisionally assign IgG concentrations in a pneumococcal reference serum to
      serotypes 1, 3, 6A, 12F, 14 and 23F. This assay was found to be reproducible; the
      coefficient of variation for duplicates was within 5%, and the day-to-day
      coefficient of variation was from 3 to 18% for all six serotypes. The assay
      provides a general method for standardizing human reference serum tools with
      respect to concentration of antigen-specific IgM-, IgA-, and IgG-subclass
      antibodies.

PMID- 8556497
TI  - Blood monocytes from most human immunodeficiency virus type 1-infected patients
      do not carry proviral DNA.
AB  - In blood, the CD4+ T cells of patients with human immunodeficiency virus type 1
      (HIV-1) harbor HIV-1; however, whether the CD4+ blood monocytes carry the virus
      is controversial. Tissue macrophages are known to be infected. To determine in
      blood monocytes from HIV-1-seropositive patients contain HIV-1, we separated
      monocytes and T-cell subsets by using monoclonal antibodies bound to magnetic
      beads and by monocyte adherence to glass. Monocytes were cultured with macrophage
      colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and
      interleukin-3. After 14 days in culture, cells were analyzed for the presence of
      HIV-1 antigen and multinucleated giant cells (MGCs). Freshly isolated cell
      subsets were analyzed for HIV-1 proviral DNA by PCR with modified env (SK68i and
      SK69i2) and gag (SK145i and SK150) primers. We found that (i) monocytes cultured
      without depletion of CD4+ T cells (11 of 11 patients) were HIV-1 antigen positive
      and showed dramatically increased spontaneous formation of MGCs (ii) monocytes
      cultured after depletion of CD4+ T cells (three experiments) were HIV-1 antigen
      negative and showed markedly decreased MGC formation, and (iii) in specimens from
      14 patients subsequently analyzed by PCR, purified CD4+ T cells were positive for
      HIV-1 proviral DNA in all patients. In 11 of 14 patients (79%), the monocyte
      fractions were HIV-1 proviral DNA negative, while in the remaining 3 patients,
      the monocytes were positive for HIV-1 proviral DNA. In conclusion, the major
      reservoir for HIV-1 infection in human peripheral blood is the CD4+ T cell (14 of
      14 cases).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556498
TI  - Interleukin-2-inducible natural immune (lymphokine-activated killer cell)
      responses as a functional correlate of progression to AIDS.
AB  - The functions of natural killer (NK) cells and their interleukin-2-deducible
      counterparts, lymphokine-activated killer (LAK) cells, are often impaired in
      human immunodeficiency virus (HIV)-infected individuals. A statistical approach
      was used to establish if changes in LAK activity were associated with antiviral
      drug therapy, HIV-1 burden, or lymphocyte subset alterations. Our study group
      included 61 HIV-positive subjects without any opportunistic infections (OI-), 16
      of whom received zidovudine (AZT), and 97 HIV-positive individuals with AIDS
      related infection (OI+), 50 of whom received AZT. As expected, there was a
      stepwise decrease in total lymphocyte numbers in OI+ groups as a result of the
      selective loss of CD4+ cells. The groups receiving AZT therapy had fewer CD4+
      cells but lower circulating p24 antigen levels than corresponding untreated
      groups did. No significant changes in the relative proportions or absolute
      numbers of CD56+ subsets in HIV-positive groups could be ascribed to OI status or
      AZT intervention. LAK cell cytotoxic responses, measured as LU20 values (which
      give a measure of 20% cytolysis of target cells), lysis per unit CD56+ NK cell,
      or lysis per unit blood volume, declined in OI+ groups. No main or interactive
      effects of AZT therapy on LAK activities were observed. Multivariate general
      linear models were used to determine the interactive effects of NK- and T-cell
      subsets on measured LAK cell numbers were added negative and positive predictors
      of LAK activity, respectively. These findings indicate that declines in NK
      mediated LAK cell responses serve as functional correlates of progression in HIV
      infected individuals.

PMID- 8556499
TI  - Evidence of subtype-specific antibodies to antigenic epitopes in the NS5 region
      of hepatitis C virus in the circulation of patients with chronic hepatitis C.
AB  - The antigenicity of the NS5 region of type 1 hepatitis C virus (HCV) was
      investigated by epitope mapping of the region spanning amino acids 2530 to 2723
      of the HCV polyprotein. Six antigenic regions were recognized by anti-HCV
      positive sera from individuals with chronic hepatitis C in a modified enzyme
      linked immunosorbent assay with synthetic oligopeptides. Five of these regions
      demonstrated intra-type 1 sequence variations defining subtype 1a and 1b HCV
      sequences. The region between amino acids 2623 and 2634 allowed testing of
      subtype-specific anti-NS5 antibodies; serological reactivity to subtypes 1a and
      1b was observed in 27 and 61%, respectively, of 150 cases with chronic hepatitis
      C. Simultaneous reactivity to subtypes 1a and 1b was found in 23% of the
      patients. Detection of subtype-specific anti-NS5 antibody correlated in more than
      80% of the cases with the HCV genotype (subtypes 1a and 1b) analyzed by PCR
      amplification of the NS5 sequence. These data provide evidence of the existence
      of a subtype-specific anti-NS5 response in the circulation of patients with
      chronic hepatitis C.

PMID- 8556500
TI  - Humoral response to mycobacterial heat shock proteins in patients with
      constrictive pericarditis caused by tuberculosis and its implications for
      pathogenesis.
AB  - Tuberculous pericarditis is one of the commonest causes of cardiac failure in
      Transkei and the surrounding regions in southeast Africa. About 20% of patients
      with clinically diagnosed tuberculous pericardial effusion go on to develop
      pericardial fibrosis (i.e., construction), a complication which is associated
      with significant mortality and morbidity. The pathological mechanisms underlying
      this aberrant inflammatory response are poorly understood, and there is a lack of
      reliable pointers (clinical or laboratory) in predicting the likelihood of
      development of constriction. We studied the humoral response to mycobacterial
      heat shock proteins (65 and 71 kDa) in 25 patients with culture-positive
      tuberculous pericardial effusion and found a significant correlation between high
      anti-mycobacterial hsp60 antibody titers (before treatment) and subsequent
      development of fibrosis (P = 0.035 by logistic regression), which is independent
      of the effect of the use of prednisolone as adjuvant therapy. Possible mechanisms
      underlying the pathogenesis of pericardial constriction in tuberculosis are
      postulated.

PMID- 8556501
TI  - Granulocyte colony-stimulating factor does not enhance phagocytosis or
      microbicidal activity of human mature polymorphonuclear neutrophils in vitro.
AB  - The direct effects of human granulocyte colony-stimulating factor (hG-CSF) on
      mature polymorphonuclear neutrophils (PMNs) in vitro were studied with regard to
      chemotaxis, superoxide production, and phagocytosis and microbicidal activity
      against the following viable microorganisms: Staphylococcus aureus, serum
      resistant Pseudomonas aeruginosa, and Candida albicans. Recombinant hG-CSF (rhG
      CSF) acted as a chemoattractant for human PMNs in a dose-dependent manner. The
      chemotactic response of PMNs to N-formyl-methionyl-leucyl-phenylalanine (FMLP)
      was not enhanced by rhG-CSF at any of the concentrations used. rhG-CSF did not
      induce the generation of superoxide by itself. However, rhG-CSF was able to prime
      human PMNs and to enhance O2- release stimulated by FMLP in a dose-dependent
      manner. rhg-CSF did not enhance phagocytosis or killing of the three species of
      microorganisms by normal PMNs. With PMNs obtained from patients who had
      hematological disorders or solid tumors, no enhancement of the microbicidal
      activity was observed in most cases. Microbial killing mediated by PMNs depended
      on the ratio of PMNs to target organisms. We concluded from these facts that the
      most important effect of rhG-CSF was to increase the number of the peripheral
      PMNs and not to enhance the functions of mature PMNs.

PMID- 8556502
TI  - Immunochemical analysis of the H and M glycoproteins from Histoplasma capsulatum.
AB  - The H and M antigens of Histoplasma capsulatum are glycoproteins, and both
      possess epitopes found on the C antigen, a cross-reactive galactomannan shared by
      the major genera of systemic dimorphic fungi. We modified the H and M
      glycoproteins by chemical and enzymatic digestion to determine the relative
      contributions of the carbohydrate and protein moieties to the immunological
      reactivities and the apparent molecular weights of these antigens.
      Endoglycosidases with known action patterns were used to determine the nature of
      the glycopeptide bonds in the H and M antigens. The effects of these treatments
      were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      lectin binding, and enzyme-linked immunoelectrotransfer blots probed with
      polyclonal and monoclonal antibodies (MAbs). Oxidation with 100 mM periodate
      destroyed the common fungal epitope recognized by MAb CA1-CB4 and nearly all of
      the concanavalin A-binding sites on both the H and M antigens; it also caused the
      molecular mass of the M antigen to shift from 94 to 88 kDa. Treatment of samples
      with O-glycanase had little, if any, effect on the H and M glycoproteins. On the
      other hand, treatments with endo-beta-N-acetylglucosaminidase H, and particularly
      peptide N-glycoproteins F (PNGase F), produced pronounced shifts in the M(r) but
      did not completely eliminate concanavalin A- or MAb CA1-CB4-binding sites. PNGase
      F treatment caused the molecular mass of the H antigen to shift from 116 to 94
      kDa and that of the M antigen to shift from 94 to 74 kDa. The susceptibilities of
      the H and M glycoproteins to endo-N-acetyl-beta-D-glucosaminidases suggest that
      their glycosidic moieties are N linked.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556503
TI  - Synergistic effects of gamma interferon on inflammatory mediators that induce
      interleukin-6 gene expression and secretion by human retinal pigment epithelial
      cells.
AB  - The retinal pigment epithelial (RPE) cell is a potent regulatory cell within the
      retina. It helps to maintain normal retinal activity, and following gamma
      interferon (IFN-gamma) exposure, it may express major histocompatibility complex
      class II molecules and function as an antigen-presenting cell. Since interleukin
      1 (IL-1) and IL-6 are potent cytokines observed in ocular inflammatory processes,
      we initiated studies to evaluate conditions which enable RPE cells to produce
      these cytokines. Cultures of human RPE cells from two eye donors were established
      and characterized, and enzyme immunoassays were employed to screen for IL-1 and
      IL-6 production. Treatment of RPE cells with lipopolysaccharide (LPS) or
      recombinant tumor necrosis factor alpha, IL-1, or IFN-gamma resulted in a
      significant level of secretion of IL-6. In contrast, treatment with recombinant
      epidermal growth factor, basic fibroblast growth factor, platelet-derived growth
      factor, or transforming growth factor alpha, or LPS can dramatically augment the
      secretion of IL-6 by RPE cells. Thus, these inflammatory mediators can act alone
      or synergistically with IFN-gamma to activate RPE cells and dramatically increase
      the expression and secretion of IL-6. In contrast, IL-1 was not detected
      following stimulation with any of the above-mentioned cytokines or LPS.
      Characterization of IL-6 protein production by RPE cells revealed that 98% of the
      protein is promptly secreted by the cell, its induction is dependent upon the
      time and concentration of the stimulant, and the continuous presence of the
      stimulant is required for IL-6 production. Moreover, Western blot (immunoblot)
      analysis of secreted proteins revealed that IL-6 was produced in multiple
      molecular forms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556504
TI  - Characterization of enterotoxigenic Bacteroides fragilis by a toxin-specific
      enzyme-linked immunosorbent assay.
AB  - Within the past decade, certain strains of Bacteroides fragilis have been
      associated with diarrhea in humans and cytotoxic activity on certain colon
      carcinoma cell lines. An enzyme-linked immunosorbent assay (ELISA) for detecting
      the enterotoxin of B. fragilis in cultures and stools was developed by using high
      titer monospecific goat and rabbit antitoxins in an indirect format. The lower
      limit of detection for purified toxin was approximately 0.05 micrograms/ml; the
      linear range was from 0.05 to 10 microgram/ml. Using the ELISA to screen cultures
      of toxigenic and nontoxigenic strains of B. fragilis, we observed 100%
      correlation with 16 known toxigenic strains which had various cytotoxic
      activities on HT-29 cells. In addition, we found 6 of 62 previously untested
      strains also to be positive in both assays. Stability studies revealed that
      although the cytotoxic activities of crude and purified toxin preparations
      incubated at elevated temperatures were rapidly lost, the ELISA responses were
      not significantly reduced. Sodium dodecyl sulfate(SDS)-polyacrylamide gel
      electrophoresis and SDS-capillary electrophoresis showed that the purified toxin
      autodigested to several stable peptides. Studies on partially purified membranes
      from the toxigenic strains revealed the presence of several membrane-associated
      components which were noncytotoxic but strongly immunoreactive in the ELISA.
      Preliminary studies with spiked feces indicated that the ELISA may be useful for
      screening not only cultures for the enterotoxigenic B. fragilis but also stool
      specimens. Ongoing studies are focusing on determining the nature of the toxin's
      apparent proteolytic capabilities and investigating the feasibility of using the
      ELISA on stool specimens from healthy and diarrheic humans.

PMID- 8556505
TI  - Soluble human complement receptor type 1 inhibits complement-mediated host
      defense.
AB  - Soluble complement receptor type 1 (sCR1) is a powerful inhibitor of complement
      activation. Because of this ability, sCR1 may prove to be an important
      therapeutic agent that can be used to block the immunopathologic effects of
      uncontrolled complement activation in a variety of clinically significant
      disorders. Although several previous studies have examined the ability of sCR1 to
      inhibit complemented-mediated immunopathologic damage, there is no information on
      its ability to interfere with the host's defense against infection. In the
      current experiments sCR1 exerted a concentration-dependent inhibitory effect on
      the phagocytosis of Streptococcus pneumoniae by human polymorphonuclear
      leukocytes in vitro. Not only di sCR1 inhibit complement-dependent opsonization
      of the pneumococcus but at higher concentrations it also inhibited the ingestion
      of bacteria which had been previously opsonized. Furthermore, when rats were
      injected with sCR1, it inhibited both their serum hemolytic activity and serum
      opsonic activity in a dose-dependent fashion. Finally, for rats treated with
      sCR1, the 50% lethal dose was S. pneumoniae and Pseudomonas aeruginosa. These
      data demonstrate that sCR1 significantly inhibits complement-mediated host
      against bacterial infection.

PMID- 8556506
TI  - DNA-based HLA typing of nonhematopoietic tissue used to select the marrow
      transplant donor for successful treatment of transfusion-associated graft-versus
      host disease.
AB  - Transfusion-associated graft-versus-host disease (TAGVHD) is a rare and usually
      fatal complication of blood transfusion which can arise when immunocompetent
      lymphocytes from the donor of a cellular blood product are transfused into a
      severely immunocompromised recipient. We describe the case of an 8-month-old male
      with a severe combined immunodeficiency syndrome who developed TAGVHD after
      receiving an unirradiated transfusion. Serologic HLA typing of the parents, the
      patient, and the blood donor demonstrated the foreign origin of circulating
      lymphocytes, confirming the diagnosis of TAGVHD. The manifestations of TAGVHD did
      not respond to medical immunosuppressive therapy, and bone marrow transplantation
      was planned to treat the underlying immunodeficiency as well as the TAGVHD. By
      using DNA-based class I and class II HLA typing, the child's HLA type was
      determined from nonhematopoietic tissues. This information proved critical in
      selecting the bone marrow donor. The child received immunosuppression,
      myeloablation, and a T-depleted, maternal bone marrow graft mismatched at one HLA
      class II allele. Trilineage hematopoietic engraftment occurred within 3 weeks,
      and the child remains clinically stable with no evidence of TAGVHD more than 2
      years after the transplant. This case illustrates that TAGVHD can be successfully
      treated by allogeneic bone marrow transplantation and that DNA-based HLA typing
      can play a unique role in the diagnosis and management of TAGVHD.

PMID- 8556507
TI  - Characterization of circulating CD4+ CD8+ lymphocytes in healthy individuals
      prompted by identification of a blood donor with a markedly elevated level of
      CD4+ CD8+ lymphocytes.
AB  - During flow cytometric analysis of lymphocytes from healthy donors, we identified
      a donor (donor A) with 22% CD4+ CD8+ cells (versus values of < 4% for 65 other
      controls). To determine if CD4+ CD8+ cells from donor A and other controls were
      similar, we first defined the phenotypic profile of control CD4+ CD8+ cells.
      Enriched CD4+ CD8+ cell populations for 10 controls were prepared by a two-step
      positive selection scheme with anti-CD4-coated magnetic beads and anti-CD8-coated
      culture flasks; the selected population averaged 69% CD4+ CD8+ cells and 31% CD4+
      CD8- cells. For all 10 controls, two subsets of CD4+ CD8+ cells, CD4dim CD8bright
      and CD4bright CD8dim, were observed. Phenotypic profiles of these two CD4+ CD8+
      subsets were defined by pairing anti-CD8 with other monoclonal antibodies, and
      the profiles were compared with each other and with those of CD4+ CD8-, CD4-
      CD8bright, and CD4- CD8dim cells. CD8bright and CD4bright CD8dim cells differed
      in their proportions of CD62-L+ cells and in their levels of CD11a and CD2
      expression. Both CD4+ CD8+ subsets resembled CD4+ CD8- cells in CD45RA, CD45RO,
      and CD25 expression; the comparable CD- CD8+ cells in CD62-L expression; and CD4-
      CD8bright cells in CD11b, CD11b, CD16/56, and CD28 expression. CD38 expression in
      both CD4+ CD8+ subsets was decreased compared with those of other cell subsets.
      Whereas control CD4+ CD8+ cells averaged 33% CD4dim CD8bright, CD4+ CD8+ cells
      from donor A were > 90% CD4dim CD8bright. Donor A CD4dim CD8bright cells
      exhibited proportional decreases in CD25 and CD62-L expression and increases in
      CD11b and CD54 expression compared with those of control CD4dim CD8bright
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556508
TI  - Prenatal diagnosis of heterozygous deficiency of the second component of
      complement.
AB  - Genetically determined C2 deficiency predisposes an individual to recurrent and
      invasive bacterial infections as well as a variety of rheumatic diseases. Most C2
      deficient individuals carry the same 28-bp deletion in the sixth exon of the C2
      gene. The present article reports the first prenatal analysis of a sibling of a
      C2-deficient patient; the sibling was found to be a heterozygous carrier of the
      28-bp deletion of C2.

PMID- 8556509
TI  - Immunoblot analysis of humoral immune responses to Mycobacterium bovis in
      experimentally infected cattle: early recognition of a 26-kilodalton antigen.
AB  - Development of a serodiagnostic test for bovine tuberculosis necessitates an
      understanding of the humoral immune responses of animals following infection with
      Mycobacterium bovis. The antibody responses in groups of calves challenged
      intranasally with different doses of M. bovis (approximately 10(2), 10(4), and
      10(6) CFU) or placed in contact with the infected animals were analyzed by
      immunoelectrophoretic blotting in which a whole-cell sonicate of M. bovis was
      utilized as an antigen. Antibody responses were evident early in infections in
      which calves were exposed to high doses of M. bovis, while in groups exposed to
      lower doses, the time until antibody was detected increased as the challenge dose
      decreased. In cattle exposed to M. bovis, immunoblot analysis showed antibody
      responses to three main antigens of 26, 22, and 16 kDa. It was further
      demonstrated that antibody responses to the 26-kDa antigen appeared earliest in
      the course of infection. Preliminary investigations in this study have identified
      a 26-kDa antigen for potential use in improved serodiagnosis by enzyme-linked
      immunosorbent assays.

PMID- 8556510
TI  - Human Immunoglobulins for intravenous use and hepatitis C viral transmission.

PMID- 8556511
TI  - Effect of hematopoietic growth factors on human blood monocytes/macrophages in in
      vitro culture.
AB  - The production of mature monocytes/macrophages is regulated by a group of
      hematopoietic growth factors, or colony-stimulating factors (CSF). We
      investigated the in vitro effect of human hematopoietic growth factors on human
      blood monocyte/macrophage differentiation and proliferation in short- and long
      term in vitro cultures. The addition of macrophage CSF, granulocyte-macrophage
      CSF, and granulocyte CSF and interleukin-6 and interleukin-3 growth factors to
      monocyte/macrophage cultures induced morphological changes in cultured cells,
      including enhancement of cell growth and the formation of multinucleated giant
      cells, spindle-like cells, and fibroblast-like cells. In addition, CD4 and HLA-DR
      antigen expression was down regulated by the addition of growth factors without a
      change in the expression of other surface antigens, including CD3, CD11B, CD14,
      CD15, NK H1, and B1. The proliferating cell nuclear antigen was not detected in
      growth factor-treated nonadherent monocytes/macrophages in long-term cultures.
      Bromodeoxyuridine was incorporated in the adherent monocytes/macrophages, and
      intense staining in the small rounded cells which occur above the adherent cells
      in these cultures was observed after a 72-h pulse, indicating that
      monocytes/macrophages are slowly dividing cells.

PMID- 8556512
TI  - Human antibody response to the B oligomer of pertussis toxin.
AB  - To determine whether antibodies to the B oligomer of pertussis toxin (PT) were
      present in patients diagnosed with pertussis or vaccinees who had received
      diphtheria-tetanus-whole-cell pertussis vaccine, we analyzed serum samples from 5
      patients and 10 vaccinees by both enzyme-linked immunosorbent assay (ELISA) and
      Western immunoblotting techniques. Antibodies to the B oligomer were detected by
      ELISA in all samples containing antibodies to holotoxin. Western immunoblotting
      procedures were less efficient than ELISA techniques for detecting antibodies to
      the B oligomer. Antibodies which inhibit the ability of the B oligomer to
      agglutinate erythrocytes were detected in purified human immunoglobulin
      preparations. In addition, serum samples containing antibodies to PT inhibited
      the binding of purified B oligomer and holotoxin to a 165-kDa glycoprotein which
      has been considered a potential PT receptor in Chinese hamster ovary (CHO) cells.
      These results suggest that antibodies to the B oligomer contribute to the human
      serologic response to PT, but their detection and characterization require
      appropriate methods.

PMID- 8556513
TI  - A prospective study of antibody responses to defined epitopes of human
      papillomavirus (HPV) type 16 in relationship to genital and anorectal presence of
      HPV DNA.
AB  - The aim of this study was to investigate whether antibody responses against
      synthetic peptides derived from genital human papillomavirus (HPV) proteins are
      associated with laboratory-proven genital and anorectal HPV infection. In this
      study, 158 heterosexual patients (110 women and 48 men) were followed
      prospectively. At each visit we collected serum samples as well as specimens from
      several sites in the anogenital area for detection of HPV type 6/11 (HPV-6/11), 
      16, -18, and -33 DNAs by PCR. Immunoglobulin A (IgA) and IgG responses against
      disrupted bovine papilloma virions and eight different synthetic peptides derived
      from HPV-6/11, -16, and -18 were determined for serum samples from the first and
      the last visits. The subjects attended the Municipal Sexually Transmitted Disease
      Clinic in Amsterdam, The Netherlands, two to seven times (mean, four times) at
      approximately 4-month intervals. Women were monitored over a period of 155 person
      years, and men were monitored over 65 person-years. The magnitudes of the IgA
      responses against HPV-16 late protein epitopes L1:13, L1:31, and L2:49 were
      significantly higher in the sera from the last visit among the currently HPV DNA
      positive participants than in HPV DNA-negative persons (P = 0.02). When the
      persons positive for any HPV type at any time during the follow-up period were
      compared with those who were negative at all times during the follow-up period,
      we also found a significant elevation of IgA responses against L1:31 and L2:49 (P
      = 0.04 and 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556514
TI  - Genetic diversity in human Fc receptor II for immunoglobulin G: Fc gamma receptor
      IIA ligand-binding polymorphism.
AB  - Fc gamma receptors, and in particular genetic variation in these receptors, are
      important in disorders of hose defense, immunohematologic disease, and systemic
      autoimmune diseases. We investigated the His-Arg (CAT/CGT) polymorphism at codon
      131 of the Fc gamma receptor IIA gene, which influences ligand binding by the
      receptor. Previously, individuals had been classified phenotypically on the basis
      of differential binding of murine immunoglobulin G1, but the Fc gamma receptor
      IIA genotype distribution has not been reported. We used selective PCR-based
      sequence analysis of genomic DNA to determine the distribution in healthy
      individuals. For African-Americans, the genotype distribution was determined to
      be A/A (14%), A/G (60%), and G/G (26%); for Caucasian Americans, the distribution
      was A/A (30%), A/G (51%), and G/G (19%). These data correlate well with
      phenotypic data. We implemented a nonradioactive single-stranded conformational
      polymorphism analysis to rapidly identify all three genotypes. The PCR-single
      stranded conformational polymorphism analysis method will facilitate studies of
      the genotype distribution in individuals with disorders of immune function.

PMID- 8556515
TI  - Serologic diagnosis of human monocytic ehrlichiosis by immunoblot analysis.
AB  - Human monocytic ehrlichiosis is caused by Ehrlichia chaffeensis, an intracellular
      bacterium probably transmitted by the tick Amblyomma americanum in the United
      States. Despite its lack of specificity in discriminating among infections by
      closely related Ehrlichia spp., immunofluorescence assay (IFA) is the most
      frequently used serological diagnostic method. To improve the specificity of the
      serological diagnosis, we compared antigenic profile of E. canis and E.
      chaffeensis antigen with homologous and heterologous sera, searching for the
      specificity of the presence of low-molecular-weight proteins. Western immunoblot
      analysis of IFA-positive human sera revealed 27- and 29-kDa proteins which are
      not found in E. canis IFA-positive sera from dogs. IFA-positive sera from dogs
      revealed a low-molecular-weight group of proteins (20 to 28 kDa) which were not
      found in human E. chaffeensis-positive sera except for a weak band at 22 kDa. The
      presence o antibodies directed against the 27- and 29-kDa proteins on Western
      blots is specific for E. chaffeensis infection, and we suggest that the Western
      blot might complete IFA in cases with low positive predictive value.

PMID- 8556516
TI  - Production of interferons in human placental trophoblast subpopulations and their
      possible roles in pregnancy.
AB  - The human cytotrophoblasts are the first fetal cells to arise during
      embryogenesis and are the progenitor cells to villous (noninvasive),
      syncytiotrophoblast (noninvasive), "intermediate" extravillous (invasive), and
      "anchoring" extravillous (invasive) trophoblast subpopulations. These trophoblast
      subpopulations were isolated from first- and third-trimester placentae and were
      stimulated with Sendai virus, granulocyte-macrophage colony-stimulating factors
      (GM-CSF), and platelet-derived growth factor (PDGF) to produce interferons
      (IFNs). GM-CSF and PDGF induced very low levels of IFN in first-trimester
      extravillous and villous trophoblast subpopulations. Highly proliferating and
      invasive intermediate extravillous trophoblast cultures produced five- to
      eightfold more IFNs than villous trophoblast cultures and two- to fivefold more
      IFN than the syncytiotrophoblast cultures when stimulated with Sendai virus.
      Syncytiotrophoblast cultures produced higher levels of IFNs (up to twofold) than
      villous trophoblast cultures when stimulated with the same virus. Pretreatment of
      first-trimester extravillous and villous trophoblast cultures with GM-CSF and
      PDGF followed by infection with Sendai virus resulted in greater IFN production
      than when the cultures were stimulated with virus alone. The levels of IFN
      produced were dependent on the type of trophoblast, the type of inducer, and the
      stage of differentiation of the trophoblasts. The purified trophoblast IFNs have
      potent antiviral activities when assayed on human amniotic WISH cells, and they
      inhibited proliferation of normal trophoblasts and trophoblast-derived malignant
      cells in vitro without any toxicity. Furthermore, the trophoblast IFNs activated
      NK cell activity and suppressed mitogen-stimulated lymphocyte proliferation at
      concentrations of between 10 and 1,000 IU/ml. The possible functions of the
      trophoblast IFNs during pregnancy are discussed with respect to human placental
      and fetal protection and development.

PMID- 8556517
TI  - Rapid culture and quantitation of human immunodeficiency virus type 1 from
      patient cells without the use of mitogen-stimulated donor cells.
AB  - We report the development of a rapid, sensitive virus culture method for direct
      quantitation of human immunodeficiency virus (HIV) in peripheral blood
      mononuclear cells (PBMCs). This new method involves culturing 10(7) PBMCs from
      HIV-seropositive persons in 10 ml of medium containing phorbol 12-myristate 13
      acetate and interleukin-2. Both agents stimulate cell activation and hence viral
      replication. Cell-associated virus and free virus are quantitated by a
      commercially available HIV p24 antigen capture enzyme immunoassay. Detection of
      cell-associated p24 antigen by flow cytometry was less sensitive than by the
      enzyme immunoassay. In this preliminary study, HIV was detected in 20 of 23 HIV
      seropositive patients and in none of the 11 HIV seronegative low-risk
      individuals. One HIV-seronegative person with Guillain-Barre syndrome following
      high-risk activity was found to be rapid-HIV-culture positive. The overall
      sensitivity and specificity were 87 and 100%, respectively. By comparing the
      quantity of virus produced in infected cells with the amount of virus produced in
      chronically infected U1 monocytes and ACH-2 lymphocytes stimulated with phorbol
      12-myristate 13-acetate and interleukin-2, the approximate number of infected
      cells per sample is calculated. In the same patient specimens, quantitation of
      the number of HIV infected cells by the HIV rapid-culture method correlated with
      the results of the 21-day cell dilution coculture assay (correlation coefficient
      r = 0.5; 95% confidence interval, 0.07 to 0.77). Advantages of the rapid HIV
      culture include no requirement for donor PBMCs or change of media, shortened
      culture time, and the ability to detect p24 viral antigen from cell-associated
      virus for quantitation of viral load.

PMID- 8556518
TI  - Placental transfer of immunoglobulin G subclasses.
AB  - The concentrations in cord blood of total immunoglobulin G (IgG) and the four
      subclasses of IgG were measured in 34 fetuses at a mean gestational age of 25
      weeks (range, 18 to 35 weeks). The blood samples were obtained by percutaneous
      umbilical blood sampling, and results were compared with the respective IgG
      subclass concentrations of the mothers. The efficiency of transplacental transfer
      of the different IgG subclasses was determined. Transfer of IgG1 and IgG4 was
      found to be significantly more efficient than that of IgG3 and IgG2. IgG2 was the
      subclass least efficiently transferred from mother to fetus. These differences
      may partly explain the susceptibility of newborns to various pathogens, such as
      streptococcus group B.

PMID- 8556519
TI  - Antibody-dependent enhancement of respiratory syncytial virus infection by sera
      from young infants.
AB  - Respiratory syncytial virus (RSV) convalescent-phase sera and control sera from
      both infants ( < 6 months) and older individuals (1.5 to 90 years) were assayed
      for RSV-specific antibodies by neutralization, in vitro enhancing activity, and
      immunoprecipitation. Enhancement of RSV infection in U937 cells was demonstrated
      with convalescent-phase sera and was shown to be dependent on Fc receptors by
      blocking with human immunoglobulin G (P < 0.01). Convalescent-phase sera from
      infants enhanced infection at concentrations closer to physiological ones (10(-1)
      to 10(-3) dilutions of serum), while convalescent-phase sera from older
      individuals enhanced infection only at much lower concentrations (10(-3) to 10(
      6) dilutions of serum; P < 0.01). To our knowledge, this is the first report of
      RSV-enhancing antibody activity in the sera of infants. The observed enhancing
      activity and the low neutralizing antibody levels are confined mostly to
      convalescent-phase sera from infants aged 0 to 6 months, suggesting that these
      factors may contribute to the increased severity of RSV disease frequently
      encountered in young infants.

PMID- 8556520
TI  - Major antigenic region on the integrase (IN) protein of human immunodeficiency
      virus type 1 determined by reactivity of human sera and a monoclonal antibody to
      IN protein.
AB  - The gene encoding the integrase (IN) protein of human immunodeficiency virus type
      1 (HIV-1) was expressed in vaccinia virus and Escherichia coli, and sera from 55
      HIV-1-infected individuals were examined for immunoreactivity to the recombinant
      IN proteins by Western immunoblot. Approximately 98% (54 of 55) of the HIV-1
      infected individuals showed reactivity to both the full-length IN protein of 32
      kDa (IN32 protein) and the carboxy-terminal portion of the IN protein (IN17
      protein). Serum samples from only 6 of the 54 antibody-positive individuals and a
      monoclonal antibody against the IN protein, 6F4, reacted with the amino-terminal
      portion of the IN protein (IN15 protein). The eight AIDS patients tested were
      seronegative to IN15 protein. The magnitude of reactivity to the recombinant IN
      proteins decreased slightly in the progression of the course of HIV-1 infection.
      These results suggest that a B-cell immunodominant epitope(s) on the IN protein
      is located on the C-terminal IN17 portion and that a minor epitope(s)
      recognizable by 6F4 and by rare patients is on the N-terminal IN15 portion.

PMID- 8556521
TI  - Endotoxin levels in sera of elderly individuals.
AB  - The endotoxin levels in serum of 377 72-year-old individuals were quantitated.
      The study population was a representative sample of this age group and was
      participating in a general study of health and disease among the elderly in
      Goteborg, Sweden. The endotoxin levels in serum were quantified by the
      chromogenic Limulus amebocyte lysate assay and were correlated with the health
      status and laboratory findings for each individual. The mean endotoxin levels (+/
      1 standard deviation) in men and women, when excluding four outliers, were 6.6
      +/- 3.8 and 6.9 +/- 3.8 pg/ml, respectively. All included, 21.5% of individuals
      had endotoxin levels equal to or above the sensitivity limit of 10 pg/ml. Strong
      positive correlations were found between endotoxin levels and plasma
      triglycerides (P > 0.995) and between endotoxin levels and serum protein (P >
      0.9875). The endotoxin activity also correlated with mean corpuscular hemoglobin
      concentration (P < 0.005, negative correlation), body mass index (P > 0.9875),
      and decreased appetite (P > 0.9875). A high alcohol consumption was associated
      with increased endotoxin levels (P = 0.995). There are no previous studies which
      examine endotoxin levels in serum samples from individuals representative of the
      population. This study showed that elderly individuals had the same mean level of
      endotoxin as has been found in other age groups. The increased endotoxin levels
      seen in heavy drinkers may be explained by a decreased ability of the liver to
      remove endotoxin. The correlations found between endotoxin and triglycerides,
      protein, mean corpuscular hemoglobin concentration, decreased appetite, and body
      mass index are discussed.

PMID- 8556522
TI  - Silicone-specific blood lymphocyte response in women with silicone breast
      implants.
AB  - A blinded cross-sectional study was carried out with 99 women, 44 of whom had
      silicone breast implants. Group I consisted of 55 healthy volunteer women without
      breast implants; group II comprised 13 volunteer women with breast implants or
      explants who felt healthy; group III comprised 21 volunteer women with breast
      implants who had chronic fatigue, musculoskeletal symptoms, and skin disorders;
      and group IV comprised 10 women who had their prostheses explanted but still
      presented with clinical symptoms similar to those of the women in group III.
      Proliferative responses of peripheral blood mononuclear cells from all 99 women
      were measured by [3H]thymidine uptake after exposure to SiO2 silicon, or silicone
      gel. The levels of proliferative responses were expressed as stimulation indices,
      which were obtained by dividing the counts per minute of stimulated cells by the
      counts per minute of unstimulated cells. Abnormal responses to SiO2, silicon, or
      silicone gel were defined as a stimulation index of > 2.8, > 2.1, or > 2.4,
      respectively. Abnormal responses were observed in 0% of group I, 15% of group II,
      29% of group III, and 30% of group IV (P < 0.0005 for group I versus groups II
      and IV). Thirty-one percent of symptomatic women with silicone gel breast
      implants had elevated serum silicon levels ( > 0.18 mg/liter); however, there was
      no significant correlation between abnormal cellular responses and silicon levels
      in blood serum, type of implant, time since first implantation, prosthesis
      explantation, number of implants, or report of implant leakage or
      rupture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556523
TI  - Epstein-Barr virus-transformed B cells, a potentially convenient source of
      autologous antigen-presenting cells for the propagation of certain human
      cytotoxic T lymphocytes.
AB  - Antigen-specific cytotoxic T cells (CTL) are generally elicited in vitro by
      incubation of effector cells with an appropriate major histocompatibility complex
      matched antigen-presenting cell (APC). In the case of CTL derived from inbred
      rodents, spleen cells from an animal of the same strain serve as a ready source
      of autologous major histocompatibility complex-identical APC. In outbred human
      populations, however, a convenient source of human leukocyte antigen-matched APC
      is ordinarily difficult to obtain, and for that reason human antigen-specific CTL
      may be difficult to propagate. We describe a method whereby Epstein-Barr virus
      transformed human B cells (B-LCL) serve as a convenient source of efficient APC
      for the propagation of human antigen-specific CTL. B-LCL are produced by using B
      cells from the donor under study and are thus human leukocyte antigen identical
      to the donor. Using this method, we have propagated human CD4+ Toxoplasma gondii
      specific CTL for up to 9 months in vitro, during which time the cells retained
      their functional capability.

PMID- 8556524
TI  - Isolation and characterization of a chimpanzee monoclonal antibody to the G
      glycoprotein of human respiratory syncytial virus.
AB  - Respiratory syncytial virus (RSV) is the most common cause of serious lower
      respiratory tract disease in infants and young children. In this study a
      hybridoma line secreting a chimpanzee monoclonal antibody that neutralizes RSV
      was isolated. Two chimpanzees were immunized with recombinant vaccinia viruses
      that express the RSV F or G surface glycoprotein and 1 month later were infected
      intranasally with the wild-type RSV strain A2. Peripheral blood lymphocytes
      obtained from the animals were transformed with Epstein-Barr virus, and
      lymphoblastoid cell lines that secreted anti-RSV antibodies were identified by an
      RSV antigen-binding enzyme-linked immunosorbent assay. Supernatants from RSV
      antibody-secreting lymphoblastoid cell lines were tested for in vitro virus
      neutralization before being fused to the heteromyeloma cell GLI-H7. A chimpanzee
      antibody [immunoglobulin G3(lambda) subclass] produced from a hybridoma line
      designated E1.4/2 was shown to bind to the RSV G glycoprotein and neutralize a
      panel of subgroup A viruses, but not subgroup B viruses, at low (nanomolar)
      concentrations. Mice passively immunized with this antibody were partially
      resistant to RSV strain A2 challenge. The usefulness of such antibodies in
      immunoprophylaxis and immunotherapy of RSV infection is discussed.

PMID- 8556525
TI  - Impairment of monocytic function during Trypanosoma cruzi infection.
AB  - During acute infection, Trypanosoma cruzi, the etiologic agent of Chagas'
      disease, causes immunosuppression by mechanisms that are not fully delineated.
      Since mononuclear phagocytes are major target cells in trypanosomiasis, we
      investigated monocytic function during acute T. cruzi infection. A series of
      human monocyte and macrophage hybridomas, which represent clonal expansions of
      subpopulations of human macrophages and possess many normal monocytic functions,
      were successfully infected with T. cruzi. Clones 63 and 53, chosen for stability
      in long-term culture, were studied extensively after infection with T. cruzi.
      Following infection of clone 63, the trypomastigote did not transform into the
      amastigote multiplicative form, suggesting that clone 63 did not support the
      entire T. cruzi life cycle. The typical life cycle was completed in clone 53, and
      thus, clone 53 was used in subsequent studies. Following infection, clone 53 lost
      expression of class II antigens compared with uninfected cells (DR of 2.2% versus
      29.3% and mean channel fluorescence intensity [mean channel] of 4.1 versus 30.5,
      DQ of 2.3% versus 15.6% and mean channel of 5.4 versus 11.4, and DP of 6.3%
      versus 27.2% and mean channel of 10.3 versus 33.4). The expression of Class I
      antigens (87.9% versus 82.8%; mean channel, 20 versus 120) and the adhesion
      molecules LFA-1 (72.9% versus 28.7%; mean channel, 50.7 versus 23.7) and LFA-3
      (10.8% versus 0.7%; mean channel, 20.7 versus 15.1) was increased in infected
      cells compared with that in uninfected cells. Production of interleukin-1 alpha
      was decreased and interleukin-6 production was increased in infected clone 53
      compared with those in the uninfected cells, while production of tumor necrosis
      factor alpha was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556526
TI  - Role of cytoskeletal elements in expression of monocyte urokinase plasminogen
      activator receptor, activation-associated antigen Mo3.
AB  - Peripheral blood monocytes exposed to bacterial products, phorbol esters, cyclic
      AMP, and cyclic AMP analogs express cell surface activation protein Mo3, which is
      the human urokinase plasminogen activator receptor (uPA-R). uPA-R is expressed by
      circulating monocytes from patients with multiple sclerosis (MS). We examined the
      role of cytoskeletal elements in the surface expression and subcellular
      distribution of uPA-R in nonactivated and lipopolysaccharide-activated monocytes
      and in monocytes from patients with MS. By using immunofluorescence techniques
      and confocal laser microscopy, we found that in unactivated monocytes,
      cytoplasmic uPA-R is found to one side of the nucleus, colocalizing with the
      Golgi. Upon activation with lipopolysaccharide, cytoplasmic Mo3-uPA-R becomes
      dispersed throughout the cytoplasm and projections concomitant with an increase
      in the monocyte perimeter (spreading). Cytoplasmic dispersion, as well as cell
      surface deposition, is dependent on microtubule integrity. Cell surface
      deposition of uPA-R upon activation is reduced by colchicine, which disrupts
      microtubules; however, once associated at the cell surface, uPA-R becomes
      associated with microfilaments via vinculin. Disruption of microfilaments with
      cytochalasin also alters surface expression of immunologically reactive uPA-R, as
      well as the distribution pattern. Monocytes from patients with MS display the uPA
      R distribution pattern characteristic of an activated monocyte.

PMID- 8556527
TI  - Rotavirus-specific intestinal immune response in mice assessed by enzyme-linked
      immunospot assay and intestinal fragment culture.
AB  - Primate rotavirus strain RRV and bovine strain WC3 or reassortants made between
      these animal viruses and human rotaviruses have been administered to infants as
      candidate vaccines. We compared RRV and WC3 in a murine model of oral infection.
      We determined the relative capacities of these viruses to induce a virus-specific
      humoral immune response by intestinal lymphocytes as tested by enzyme-linked
      immunospot assay, intestinal fragment culture, and enzyme-linked immunosorbent
      assay of intestinal contents. We found that inoculation of mice with RRV induced
      higher frequencies of virus-specific immunoglobulin A (IgA)-secreting cells in
      the lamina propria, greater quantities of virus-specific IgA in intestinal
      fragment cultures, and greater quantities of virus-specific IgA in intestinal
      secretions than did inoculation with WC3 or inactivated RRV (iRRV). The induction
      of an IgA response in serum was predictive of an IgA response among intestinal
      lymphocytes after inoculation with RRV but not WC3. In addition, large quantities
      of IgG, IgA, and IgM not specific for rotavirus were produced in fragment
      cultures from mice inoculated with RRV but not in cultures from mice inoculated
      with WC3 or iRRV. Possible mechanisms of RRV-induced polyclonal stimulation of
      intestinal B cells are discussed.

PMID- 8556528
TI  - Development, characterization, and biological properties of meningococcal
      immunotype L3,7,(8),9-specific monoclonal antibodies.
AB  - In this study, we characterize the properties of nine monoclonal antibodies
      (MAbs) that recognize meningococcal lipopolysaccharides (LPS). The following
      three specific MAbs that had not been described previously were elicited in
      BALB/c mice by using an immunotype L3,7,9 oligosaccharide-tetanus toxoid
      conjugate in combination with Quil A: 4D1-B3, 3A12-E1, and 4A8-B2. These MAbs
      reacted with L3,7,9 LPS on immunoblots and in the LPS enzyme-linked immunosorbent
      assay (ELISA) and recognised strains containing L3, L3,7, L8 (except 3A12-E1), or
      L9 LPS in the whole-cell ELISA. The six other MAbs have been described in
      previous studies (K. Saukkonen, M. Leinonen, H. Abdillahi, and J.T. Poolman,
      Vaccine 7:325-328, 1989; R.J.P.M. Scholten, B. Kuipers, H.A. Valkenburg, J.
      Danjert, W.D. Zollinger, and J.T. Poolman, J. Med. Microbiol., in press) and were
      obtained after immunization with outer membrane protein complexes containing LPS:
      MN15A11, MN15A8-1, MN15A17-1, MN11A11G, MN14F20-11, and MN14F21-11. MN15A11 was
      specific for L3,7,9 LPS and displayed properties similar to those of 3A12-E1.
      MN15A17-1, MN14F20-1, and MN11A11G were cross-reactive, and MN14F21-11 was
      specific for the L1,8 immunotype. Epitope specificities of MAbs reacting with
      L3,7,(8),9 strains were analyzed. MAbs 4D1-B3, 3A12-E1, and 4A8-B2 recognized
      phosphoethanolamine group-containing oligosaccharide-specific epitopes. MN15A11
      and MN15A17-1 were probably directed against a conformational epitope, although
      for MN5A11 recognition of an unknown L3,7,9-specific epitope in the 2-keto-3
      deoxyoctulosonic acid (KDO)-lipid A region cannot be excluded. MN15A8-1, a
      strongly cross-reactive MAb, recognized a determinant which included the KDO
      lipid A region and the more terminal saccharides.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8556529
TI  - Prevalence in Cryptococcus neoformans strains of a polysaccharide epitope which
      can elicit protective antibodies.
AB  - Monoclonal antibody (MAb) 2H1 binds to an epitope in the capsule of Cryptococcus
      neoformans that can elicit protective antibodies. The binding of MAb 2H1 to C.
      neoformans strains was studied by agglutination, immunofluorescence, and
      phagocytosis assays. The MAb 2H1 epitope was present in all 21 isolates studied,
      including those recovered from patients with recurrent infections.

PMID- 8556530
TI  - Soluble intercellular adhesion molecule-1 and E-selectin levels in plasma of
      falciparum malaria patients and their lack of correlation with levels of tumor
      necrosis factor alpha, interleukin 1 alpha (IL-1 alpha), and IL-10.
AB  - Intercellular adhesion molecule-1 and E-selectin levels were increased in the
      plasma of 60 falciparum malaria patients and were not related to levels of tumor
      necrosis factor alpha, interleukin 10, or interleukin 1 alpha. Soluble E-selectin
      was correlated to disease; its level in plasma was related to levels of both
      tumor necrosis factor soluble receptors and biological markers of disease
      severity and returned to baseline after parasite clearance faster than that of
      soluble intercellular adhesion molecule-1.

PMID- 8556531
TI  - Size variation of the major immunodominant protein of Cowdria ruminantium.
AB  - An immunodominant response is made to a polypeptide of approximately 32 kDa in
      animals infected with the rickettsial pathogen Cowdria ruminantium. We show here
      using cultured strains of the rickettsia from different geographical areas that
      the apparent size of this polypeptide varies with strain origin. Changes in the
      primary structure between strains should be considered in the design of vaccines
      and diagnostic tests based on this antigen.

PMID- 8556532
TI  - Associative spread as a mediating variable in the generation effect.
AB  - Memory retention is greater for information that is subject-produced rather than
      experimenter-provided; this enhancement has been labelled the generation effect.
      One explanation of this phenomenon, the Lexical Activation Hypothesis, assumes
      that lexical representation is a necessary condition for emergence of the effect.
      A corollary to this hypothesis, the Lexical Spread Hypothesis (Nairne, Pusen, &
      Widner, 1985), emphasises associative spread as a mediating variable. This single
      factor explanation has relied for its support exclusively on recognition
      performance. In the present study, four experiments examined the viability of
      this hypothesis, under recognition and free-recall conditions. A two-factor
      explanation is proposed to account for the findings of the present study. It
      appears that associative spread does not mediate the generation effect, when a
      recognition test is administered, but may mediate free-recall performance, where
      retrieval networks play a more significant role in memory performance. An
      alternative explanation, based on the benefits to memory retention obtained from
      disruptions of familiar orthographic patterns, is proposed to account for the
      recognition findings.

PMID- 8556533
TI  - Hindsight bias and the misinformation effect: separating blended recollections
      from other recollection types.
AB  - Questioning the presence of "truly" blended recollections, we investigated two
      cognitive phenomena: hindsight bias and the misinformation effect. At first
      glance, both phenomena seem to result from the same interference process, whereby
      the subsequent encoding of conflicting information impairs the recall of earlier
      encoded (original) material. Experiment 1 compared both paradigms using numerical
      items as material: hindsight as well as misinformation subjects revealed the same
      mean shift in their recollection of the original values. The additional analysis
      of a multinomial model, however, suggested that blended recollections occurred in
      the hindsight condition only. The misinformation effect, on the other hand,
      appeared to be based on averaging across two different recollection types.
      Experiment 2 further investigated how the memory-trace strength influences the
      likelihood for blended recollections to occur. In a misinformation procedure, one
      group of subjects read the original information twice, another group thrice.
      Again, recollections were similarly shifted towards the misinformation in both
      groups. But the multinomial model revealed that only the second group (with a
      stronger memory representation of the original information) showed blended
      recollections. Taken together, these results suggested that: (1) a minimum memory
      trace strength of the original information must be met for blended recollections
      to occur; and (2) hindsight bias and the misinformation effect--though
      superficially similar--are induced by different cognitive processes.

PMID- 8556534
TI  - Recognition failure of categorised words: further evidence of exceptions.
AB  - When subjects study a list of B items paired with A items and are tested for
      recognition of the B items alone, and then for recall of the B items given the A
      items as cues, B items that can be recalled frequently go unrecognised. The
      extent of this recognition failure is predictable from a function discovered by
      Tulving and Wiseman (1975), which relates the probability of recognising the
      recallable items to the probability of recognising all items. Two kinds of
      exceptions to this function have been discovered: encoding exceptions and
      retrieval exceptions. Very few observations of retrieval exceptions exist. Four
      experiments described in this article provide further evidence that such
      exceptions occur when the B items are categorised and the A items are the names
      of the categories. According to a contextual account of the function and
      exceptions to it, these retrieval exceptions occur because the information
      provided by the A-item cues can be largely retrieved from the B items in the
      recognition test; hence, as cues, the A items do not provide much different
      contextual information to that provided by the B items. By this account, the
      function is an empirical law; exceptions fall outside the range of this law and
      define its boundary conditions.

PMID- 8556535
TI  - Flashbulb memories: conceptual and methodological issues.
AB  - Although flashbulb memory research is now well established, it is still not clear
      exactly what researchers are referring to as flashbulbs, and what is the best way
      to address the phenomenon. There are at least two ways in which the term
      "flashbulbs" is used, and at least two conceptual approaches that can be used to
      research them. The first usage corresponds to the bold theoretical conjectures
      put forward by Brown and Kulik (1977). The second results from empirical
      classification and intuitively lacks the essence conveyed by the first meaning.
      The two approaches concentrate on the cognitive and societal aspects,
      respectively. Although these are not incompatible, they make different
      assumptions and use different methodologies. We argue that research should be
      directed towards more unified theorising, and we describe methodologies
      appropriate for this approach.

PMID- 8556536
TI  - Contextual dependencies: influence on response latency.
AB  - The present experiments were designed to examine the influence of contextual
      stimuli on perceptual-motor performance. Experiment 1 revealed that contextual
      dependencies can develop for simple perceptual-motor tasks. Furthermore, the
      extent of the dependency is mediated in part by whether the contextual
      information is removed or replaced with alternative contextual information at the
      time of test. Data from Experiment 2 and 3 showed that manipulating the potency
      of incidental contextual stimuli results in a systematic decrement or increment
      in subsequent performance, depending on whether the contextual stimuli during the
      test were changed or reinstated. To date, such an orderly influence of contextual
      stimuli is more commonly demonstrated in the animal learning literature than with
      human experimentation.

PMID- 8556537
TI  - Danegeld remembered: taxing further the coin head illusion.
AB  - Two experiments studied memory for the appearance of a Danish 20 kroner coin. The
      coin bears the portrait of Queen Margrethe II in profile, facing to the right.
      Previous studies have examined memory for British coins, which similarly bear a
      right-facing portrait of Queen Elizabeth II. They have revealed the occurrence of
      a mnemonic illusion, in that British people tend to believe the portrait faces
      left. This finding has been attributed to the occurrence of a joint coin-stamp
      schema. British stamps bear a left-facing profile of the Queen, and it is
      possible that information from the stamp predominates in the formation of the
      schema. In the case of Denmark, however, stamps bear a full-face portrait of the
      Queen. Nevertheless, the present experiments showed that the Coin Head Illusion
      is also found in Denmark. That is, the number of participants recalling the
      Queen's head as facing to the right was significantly below even the chance level
      of 50%. Further, this result occurred both for residents of Denmark and for
      visitors to Denmark. These findings suggest that the bias underlying the Coin
      Head Illusion may be a more general one than that envisaged by the joint coin
      stamp schema hypothesis.

PMID- 8556538
TI  - NAASO-SSIB annual meeting. Baton Rouge, Louisiana, October 12-17, 1995.
      Abstracts.

PMID- 8556539
TI  - [Gene diagnosis and gene therapy in China: prospectives and problems].

PMID- 8556540
TI  - [Enhanced immune functions and antitumor activity of fibroblast-mediated
      interleukin-2 gene therapy].
AB  - The aim of the present study was to establish fibroblastmediated IL-2 gene
      therapy and to observe its antitumor effect in the mouse tumor model. The IL-2
      gene-transfected fibroblasts (NIH3T3-IL-2+) secreting high level of IL-2 were
      encapsulated with collagen and then implanted i.p. into mice. Certain level of IL
      2 could be detected in murine serum for some periods, and the splenic
      proliferation, NK and LAK activities, cytokine production (IFN-v, TNF, IL-2) were
      enhanced significantly. It was of great importance that the high endogenous LAK
      activity was induced. The significant therapeutic effect of i.p. implantation of
      NIH3T3-IL-2+ on ascitic liver carcinoma-bearing mice was observed. The better
      therapeutic results could be achieved. NIH3T3-IL-2+ cells were i.p. implanted in
      combination with i.p. injection of LAK cells. These results demonstrated that
      fibroblast--mediated IL-2 gene therapy has potent antitumor effect via
      augmentation of immune functions and the antitumor effect will be more obvious
      when IL-2 gene therapy is used along with the adoptive transfer of LAK cells.

PMID- 8556541
TI  - [CD44 expression patterns in primary and secondary brain tumors].
AB  - We investigated CD44 expression patterns in five types of primary brain tumors
      and brain metastases from more than ten organs by Northern blot, reverse
      transcription/polymerase chain reaction (RT/PCR) and immunocytochemical analyses.
      The results demonstrated that all of 72 primary brain tumors examined express
      standard form of CD44 (CD44s) but none of them express CD44v. In contrast, 22 of
      26 brain metastases studied were found to express CD44v. Our data not only
      present a direct evidence of a general distribution of CD44 in primary brain
      tumors but also suggest that such expression is an extremely rare event in
      primary brain tumors. We conclude that CD44v may be a candidate marker for the
      evaluation of malignant potential of the tumors and the prognosis of cancer
      patients.

PMID- 8556542
TI  - [Analysis of heavy chain immunoglobulins gene and T-cell receptor delta gene in
      children with acute leukemia].
AB  - IgH gene, TCR delta gene rearrangements and Tal-1 gene deletion were analysed by
      using PCR, Southern blot and DNA sequencing methods in newly diagnosed BM samples
      from children with AL. The DNAs from leukemic cells in 102 children were detected
      with PCR. The results showed that IgH gene rearrangement mainly occurred in B
      Precursor ALL (37/49). Six PCR products were further analysed by DNA sequencing.
      Less homogene and bias of JH gene usage were found in analysed DNA sequences. V
      delta 2-D delta 3 rearrangement of 78 samples from ALL was analysed with PCR
      method. V delta 2-D delta 3 rearrangements mainly observed in B precursor ALL and
      related HAL. V delta 2-D delta 2-N-D delta 3 rearrangement was found in a
      sequence of PCR product. Three cases of Tal-1 gene deletion were observed in all
      studied 70 samples of AL. They all were in stage I of thymus differentiation. We
      conclud that PCR detection of those genes are useful in the diagnosis of
      clonality of AL, DNA sequencing of PCR products is the base of preparing clonal
      specific probes, and dynamic analysis of IgH gene rearrangement using PCR may be
      helpful in detection of residual clones.

PMID- 8556543
TI  - [Junctional sequences of T cell receptor V delta 2-D delta 3 or D delta 2-D delta
      3 rearrangements in acute lymphoblastic leukemia].
AB  - T-cell receptor (TCR) delta chain gene rearrangements were studied by polymerase
      chain reaction (PCR) analysis in 46 patients with acute lymphoblastic leukemia
      (ALL). Sixteen patients were found to have incomplete rearrangements of the TCR
      delta genes. Among them, 13 patients displayed V delta 2-D delta 3 rearrangement,
      while 3 had both V delta 2-D delta 3 and D delta 2-D delta 3 rearrangements. To
      determine the junctional sequence of TCR delta gene, PCR products from the 16
      patients were sequenced directly or after M13 cloning. The results showed the
      junctional sequences of TCR delta gene are highly specific for each allele. This
      sequence diversity resulted from several factors including deletion of the 3' end
      of V delta 2 or D delta 2 segment and 5' end of D delta 3 segment, the presence
      of D delta 1 or D delta 2 sequences, insertion of N nucleotides and the
      association of P nucleotides with intact V delta 2 and D delta 3 segments. In
      addition, analysis of N-nucleotide contents revealed that the amount of GC was
      much larger than that of AT (70%: 30%), indicating the insertion of N nucleotide
      was not fully random. Our sequence data confirmed that the imcomplete
      rearrangement of TCR delta gene is an early event in the lymphoid cell
      ontogenesis, and its N sequences in V-(D)-J junctional region may be used as a
      specific marker of clonality to detect the minimal residual disease (MRD) in ALL.

PMID- 8556544
TI  - [The relation between the changes of width and anionic sites of glomerular
      basement membrane and transferrinuria in rats].
AB  - The changes of width and anionic sites of glomerular basement membrane (GBM) are
      considered early changes of diabetic nephropathy. Recent work suggests that the
      normal barrier to the penetration of renal glomerular basement membrane by
      anionic plasma proteins may depend in part on the existence of negatively charged
      sites within the membrane. We evaluated the relationship between the change of
      width, anionic sites of GBM and transferrinuria in diabetic rats and normal
      controls in 1, 3, 6 months after administration by STZ. Diabetic rats revealed a
      thicken GBM (0.40-0.44microns) and reduced anionic sites (16-12/1000nm GBM
      length) compared with control rats (0.22 microns, 20-22/1000 nm GBM lenth).
      Transferrinuria was also significantly greater in diabetic rats than normals (P <
      0.01). The changes in anionic sites and transferrinuria represented defect of GBM
      charge barrier in early phase of diabetic nephropathy. Aminoguanidine attenuated
      the rise in transferrinuria and prevented GBM thickness and loss of anionie
      sites.

PMID- 8556546
TI  - [Experimental study of radioimmunotherapy for xenograft of human esophageal
      carcinoma].
AB  - Using nude mice bearing human esophageal carcinoma strain Eca 109 as models of
      tumor, we tested the therapeutic efficiency of 131I labelled monoclonal antibody
      MGb2 A 4-week experimental study was carried out in 5 treatment groups: group A,
      buffer, group B, unlabelled MGb2; group C, 131I-labelled normal mice IgG and
      group D, 131I-labelled MGb2 18.5MBq. All nude mice above were given agents
      intraperitoneally. In group E, the animals were given 131I-labelled MGb2 18.5MBq
      by intratumoral administration. The results showed that from the second week, in
      group D and E the tumor volume was remarkably decreased as compared with that of
      the other 3 groups (P < 0.01 or P < 0.05). In the fourth week the mean volume in
      group D and E were 0.55 cm3 and 0.23cm3, while in group A, the volume was
      1.43cm3. The inhibition rate of tumor growth in group D and E was higher than in
      other groups from the second week (P < 0.01), especialy in the third and fourth
      week with a mean value of 62. 4%, 61.5% and 82.2%, 83.9% respectively. There were
      no significant differences between group A, B, and C in tumor volume or growth
      inhibition rate.

PMID- 8556547
TI  - [Evaluation of operative corrigent degree of scoliosis by improved Cobb's angle
      degree of preoperative suspensive roentgenogram].
AB  - To achieve best operative result in correction of scoliosis, and avoid
      complications of the nerve system due to excess correction, we compared the
      statistical results of modified Cobb's degree of preoperative suspensive
      roentgenogram and operative corrigent degrees of 331 patients with scoliosis,
      including 219 with idiopathic scoliosis. The modified Cobb's degrees of the whole
      group was 20.15 +/- 9.41 in suspension, the operative corrigent degree was 35.34
      +/- 13.05, and the operation-suspension difference was 14.62 +/- 11.02. Referring
      to idiopathic scoliosis, it was 21.79 +/- 8.39, 37.44 +/- 11.82, 15.58 +/- 9.91
      respectively. And the statistacal study was performed according to scoliosis
      type, involved segments, curvature degree, and ages. The parameters were very
      helpful in the evaluation of currigent effect before operation.

PMID- 8556545
TI  - [Hepatitis B virus, the main cause of membranous nephropathy in China].
AB  - To investigate the role of hepatitis B virus in the pathogenesis of membranous
      nephropathy (MN) in China, we studied 67 MN patients (excluding lupas nephritis
      V) with immunoperoxidase technique. In 46 (68.2%) of the 67 MN patients, HBV
      antigens (HBsAg, HBcAg and HBeAg) were detected in their glomeruli, and HBsAg,
      the dominant antigen was detected in 45 patients (67.2%). HBV-Ag was detected
      less frequently in the older MN group (33.3%) (> 50 years old) than in the two
      younger MN groups (73.1%, 75%) (< 30 years old, 30-50 years old) (P < 0.05). 30
      randomly selected MsPGN patients were studied as controls. HBV antigens were
      detected in only 3 out of the 30 MsPGN patients. The HBV antigen positivity rate
      of the MN group was significantly higher than that of the MsPGN group (P < 0.01).
      The results suggested that HBV may be the main cause of MN in China, especially
      in those younger than 50 years, but not of MsPGN. HBsAg containing immune
      complexs (IC) may play an important role in the pathogenesis of HBV-MN.

PMID- 8556548
TI  - [Human's magnetoencephalography and normal value of auditory evoked magnetic
      field evoked by tone burst].
AB  - In magnetic shield room, 9 normal subjects were measured by
      magnetoencephalography (MEG) and auditory evoked magnetic field (AMF) with
      superconducting quantum device (SQUID). In our experiment, the magnitudes of MEG
      were between +100 fT and -100 fT and an AMF evoked with 1 kHz tone burst had 8
      stable waves. The main waves were N2, P3, N3 with latencies 65, 118, 175 ms and
      magnitudes -13, +15, -12 fT. The latencies of waves showed small deviations. The
      magnitudes of waves were about +/- 15 fT. We also found that the two lateral
      records of countralateral AMFs have revert waveforms in the last two subjects.

PMID- 8556549
TI  - [Clinical significance of fungi-bearing status of hospitalized patients].
AB  - The samples for fungi culture were collected from 11 body parts of 1109 patients
      who had been admitted to hospitals in Wuhan for more than 3 days. The body parts
      included the cavities and foramina (inner canthus, nasal vestibule, external
      auditory canal), skin (finger raphe, cubital fossa, axillary fossa, nipple), and
      mucosa (pharynx, vagina, coronary sulcus and anal canal). 201 healthy subjects
      were also examined and served as controls. It was found that the total fungus
      bearing rate in hospitalized patients was 88.73% (984/1109), while the rate in
      healthy subject was 76.62% (154/201) (X2 = 21.61). Among the hospitalized
      patients, the fungus-bearing rate in patients with leukemia, tumors, connective
      tissue diseases or severe infectious diseases was significantly higher than other
      patients (X2 = 4.30-9.87). In the hospitalized patients, the body parts with
      highest fungus-bearing rates were cavities and foramina, 80.70% (895/1109) for
      patients and 71.64% (144/201) for healthy subjects respectively. The skin had
      lowest fungus-bearing rate. 20.02% (222/1109) and 13.43% (26/201), and the mucosa
      had a rate of 50.77% (563/1109) for patients and 32.34% (65/201) respectively.
      The fungi in the hospitalized patients included 1884 strains (mean = 1.92 strains
      per case) in which the Candida accounted for 29.78% (561/1884) and Aspergilla
      24.31% (458/1884) and those identified in healthy subjects covered 234 strains
      (mean = 1.52 strains per person) in which Penicillia accounted for 45.30%
      (106/234) and Saccharomycetes 26.07% (61/234). The patients who had been
      hospitalized for 3-10 days and over 20 days had higher fungus-bearing rate as
      compared with those who had been hospitalized for 10 to 20 days (X2 = 5.633
      97.09). The patients before the administration of antibiotics and adrenocortical
      steroid and those who had been given these medicines for over 20 days had a
      higher fungus-bearing rate than those who had been on these medicines for 1-20
      days.

PMID- 8556550
TI  - [Multidrug resistance--genes and chemotherapy of ovarian cancer].

PMID- 8556551
TI  - [A cross-sectional analysis on relationships between maximum oxygen uptake and
      risk factors for cardiovascular diseases].
AB  - We examined the relationships between maximum oxygen uptake (Vo2max) and
      cardiovascular risk factors including age (year), systolic blood pressure (mmHg),
      diastolic blood pressure (mmHg), serum total cholesterol level (mg/dl), serum
      high-density lipoprotein level (mg/dl), serum triglyceride level (mg/dl), blood
      glucose level (mg/dl), serum uric acid level (mg/dl), body fat (%bw), Body Mass
      Index (BMI), alcohol (points/day), cigarettes (/day), and physical activity
      (METs.exercise time/30 days). The alcohol point was defined as follows: beer
      633ml = a glass of whiskey and water - sake 180ml = 1 point, and totaled at 30
      days. The subjects of our study were 162 males (aged 40.6 +/- 13.1) and 133
      females (aged 41.3 +/- 11.1) who underwent medical and physical examinations at
      the Fukui Industrial Health Center from April, 1991 to June, 1992. As a result of
      simple correlation analysis in males, Vo2max had significantly negative
      correlations with age (r = -0.223, p < 0.01), systolic blood pressure (r = 
      0.228, p < 0.01), diastolic blood pressure (r = -0.239, p < 0.01), or serum
      triglyceride level (r = -0.258, p < 0.001), serum uric acid level (p < 0.05),
      body fat (r = -0.230, p < 0.01), and BMI (r = -0.312, p < 0.001), and was
      positively correlated with physical activity (r = -0.249, p < 0.01). On the other
      hand, in females, age (r = -0.224, p < 0.01), systolic blood pressure (r = 
      0.222, p < 0.01), diastolic blood pressure (r = -0.267, p < 0.01), serum
      triglyceride level (r = -0.261, p < 0.001), body fat (r = -0.280, p < 0.01), and
      BMI (r = -302, p < 0.001), had significantly negative correlations with VO2max.
      However, partial correlations were tested after controlling body fat, BMI,
      cigarette, alcohol, physical activity, and age, none of the factors correlated
      with VO2max significantly. These findings suggest that the risk factors for
      cardiovascular diseases are related to VO2max, and the life style has an
      influence on these correlations. Thus, VO2max may be a comprehensive indicator
      for health promotion among the working population. Furthermore a longitudinal
      study is required to determine whether the increase in VO2max is related to the
      improvement in the risk of cardiovascular diseases.

PMID- 8556552
TI  - [Returning to work after heart transplantation--mental and physical health care
      at workplaces].

PMID- 8556553
TI  - [Blood pressure and body mass index of hypertensive patients before and during
      the medication].

PMID- 8556554
TI  - Molecular cloning and immunological characterization of the house dust mite
      allergen Der f 7.
AB  - BACKGROUND: The allergen Der p 7 from Dermatophagoides pteronyssinus has been
      defined by molecular cloning and shown to be an important specificity in 50% of
      mite-allergic patients. OBJECTIVE: This study compares the cDNA sequence and
      serological reactivity of Der f 7 from D. farinae with Der p 7. METHOD: cDNA
      encoding Der f 7 was amplified by polymerase chain reaction, sequenced and
      expressed as a fusion with glutathione-S-transferase for IgE and monoclonal
      antibody binding studies. RESULTS: Der f 7 cDNA encoded a 213 polypeptide
      containing a predicted 17 amino acid leader sequence, no cysteines and a single N
      glycosylation site similar to Der p 7. The predicted 196 residue mature
      polypeptide had 86% identity to Der p 7 and a calculated molecular weight of
      22,348Da. No homologues were found in searches of the data banks. The Der f 7
      fusion protein showed a single band of 46 kDa by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and reacted with IgE antibodies in
      19/41 (46%) of sera from asthmatic children. The degree of binding was usually
      30% of that to Der p 7 consistent with the exposure of the patients to D.
      pteronyssinus. Monoclonal antibodies (WH9 and WH22) against Der p 7 reacted with
      Der f 7 but inhibition studies showed a 10-fold difference in reactivity.
      CONCLUSION: Der f 7 has a predicted 213 residue polypeptide with 86% homology and
      serological crossreactivity to Der p 7.

PMID- 8556555
TI  - Raising the pH of the pepsin-catalysed hydrolysis of bovine whey proteins
      increases the antigenicity of the hydrolysates.
AB  - BACKGROUND: Hypersensitivity to cow milk protein is frequently observed in
      infancy. Since the pH in the infant's stomach is relatively high (pH 3-4)
      compared with adults (pH 2), an incomplete digestion of the milk proteins is
      expected to occur. OBJECTIVE: The determination of the degree of hydrolysis by
      pepsin of the four main proteins of bovine whey, i.e. alpha-lactalbumin (alpha
      La), beta-lactoglobulin (beta Lg), bovine serum albumin (BSA) and bovine
      immunoglobulin G (B-IgG), in the pH range 2.0-4.0 and of the antigenic properties
      of the resulting hydrolysates. METHODS: Whey proteins were successively
      hydrolysed with pepsin at pH values ranging from 2.0 to 4.0 and with pancreatic
      enzymes at pH 7.5 using a pH-stat. The resulting hydrolysates were characterized
      by their degree of hydrolysis, and analysed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, gel permeation chromatography and
      immunologically by competitive enzyme-linked immunosorbent assay. RESULTS: In
      general, the degree of hydrolysis, the gel electrophoretic patterns, the contents
      of peptides of molecular mass > 5 kDa and the residual human-immunoglobulin E and
      G antigenicities of the hydrolysates did not differ much whether the pepsin
      incubation was done at pH 2.0 or 3.0. Pepsin incubation at pH 4.0, however,
      resulted in a decreased hydrolysis and enhanced residual antigenicity of alpha
      La, BSA and B-IgG, but not of beta Lg. CONCLUSION: The poor and slow degradation
      of the antigenic epitopes of whey proteins when pepsin digestion occurs under
      conditions that prevail in the stomach of infants could be of much importance for
      the development of cow milk hypersensitivity. The immature gastrointestinal
      mucosal barrier of infants allows large antigenic fragments of these proteins to
      pass into the systemic circulation.

PMID- 8556556
TI  - Anaphylactic reaction to lychee fruit: evidence for sensitization to profilin.
AB  - BACKGROUND AND OBJECTIVE: Due to the increasing popularity of exotic fruits in
      the Western diet, allergologists are confronted with allergic reactions to
      substances in these plants. The present report describes an anaphylactic reaction
      after the consumption of lychee fruit (Litchi sinensis). The atopic patient also
      suffers from rhinoconjunctivitis due to a sensitization against pollen of the
      Compositae family, as well as from dyspnoea after eating sunflower seeds. Our
      goals were to determine crossreactivity between antibodies against lychee fruit
      and other plants and to characterize the allergen. METHODS AND RESULTS: Specific
      IgE against lychee fruits were detected by an EAST assay. The allergen was
      characterized by immunoblot, immunoblot inhibition and EAST inhibition assays.
      Broad crossreactivity between lychee fruit and other plants was found and
      profilin identified as the protein responsible for the patient's complex allergy
      syndrome. CONCLUSION: Lychee fruit contains a significant amount of profilin.
      Consumption of this exotic fruit can cause severe anaphylactic reactions in
      patients being sensitized against the plant pan-allergen profilin.

PMID- 8556557
TI  - Dermatophagoides siboney and Blomia tropicalis--dust mites of subtropical and
      tropical areas.

PMID- 8556558
TI  - Controlling allergy with anti-idiotypic antibodies.

PMID- 8556559
TI  - Role of microcirculation in seasonal allergic rhinitis.

PMID- 8556560
TI  - Anti-inflammatory effects of long-acting beta-agonists in asthma.

PMID- 8556561
TI  - The role of airway inflammation in the pathophysiology of nocturnal asthma.

PMID- 8556562
TI  - Characterization of allergenic components from house dust mite Dermatophagoides
      siboney. Purification of Der s 1 and Der s 2 allergens.
AB  - BACKGROUND: Allergic reactions to house dust mites of the genus Dermatophagoides
      play an important role in the pathogenesis of asthma and other atopic diseases.
      Dermatophagoides siboney has been described as a species from Cuba. Together with
      D. pteronyssinus and Blomia tropicalis, it is frequently found in house dust from
      homes of asthmatics. OBJECTIVES: The aim of this study was to investigate the
      allergenic composition from the house dust mite D. siboney. METHODS: The
      characterization of D. siboney extract was performed by SDS-gPAGE and
      immunoblotting. Purification of individual components was performed by affinity
      chromatography. RESULTS: At least 16 components between 13 and 98 kDa stained by
      Coomassie Blue were found. Using a panel of 35 sera from atopic mite sensitive
      patients 13 components reacted to different extent with patient IgE. Two
      components, 25 and 14 kDa, bound to specific IgE strongly and frequently, i.e. 80
      and 91% of the patients, respectively. Affinity chromatography using
      crossreacting monoclonal antibodies to group 1 and 2 allergens resulted in
      purified preparations of 25 and 14 kDa proteins, which showed IgE-binding with
      the majority of the human sera when tested by immuno-dot. CONCLUSION: Based on
      the IgE binding profile of D. siboney and on the capacity to react with
      crossreacting monoclonal antibodies for groups 1 and 2, it is proposed to name
      these two allergens, 25 and 14 kDa, Der s 1 and Der s 2, respectively.

PMID- 8556563
TI  - Crossreactivity between Dermatophagoides siboney and other house dust mite
      allergens in sensitized asthmatic patients.
AB  - BACKGROUND: The role of Pyroglyphid mites in IgE-mediated sensitization has been
      well established. Although mites belonging to the genus Dermatophagoides dominate
      in the acarofauna of domestic dust, non-pyroglyphid mites might also be of
      clinical importance. In Cuba, Dermatophagoides siboney is found in dust
      coexisting with D. pteronyssinus and Blomia tropicalis. Dermatophagoides farinae
      is not found. Storage mites, such as Acarus siro, Lepidoglyphus destructor and
      Tyrophagus putrescentiae, might also be present. OBJECTIVES: The aim of this
      study was to investigate the allergenic relationships among the mites present in
      the environment of allergic patients in Cuba. METHODS: The crossreactivity
      between an extract of D. siboney and the above mentioned six mites was studied by
      specific IgE inhibition, using sera of mite-sensitive patients after incubation
      with serial dilutions of D. siboney. RESULTS: The inhibitory effect of D. siboney
      extract was more pronounced against D. farinae, 91%, than against D.
      pteronyssinus, 62%. Specific IgE to B. tropicalis, A. siro, L. destructor and T.
      putrescentiae were inhibited to a much lesser extent, i.e. between 47 and 58%.
      The correlation between IgE to D. siboney and IgE to D. pteronyssinus and D.
      farinae was of 0.92 and 0.90, respectively. A weaker correlation was found
      between D. siboney and L. destructor (0.7), A. siro (0.67), B. tropicalis (0.54)
      and T. putrescentiae (0.51). CONCLUSION: Thus, D. siboney seems to be most
      closely related to D. farinae.

PMID- 8556564
TI  - Human auto-anti-idiotypic antibodies to mite-specific IgE can degranulate human
      basophils in vitro.
AB  - BACKGROUND: Anti-idiotypic antibodies (anti-Ids) to specific IgE antibodies are
      formed spontaneously during an anti-allergen immune response and can be induced
      by immunotherapy. Although anti-Ids can down-regulate the production of IgE
      antibodies, at least in experimental models, their possible role in the
      modulation of target cell reactivity remains ill-defined. OBJECTIVE: The capacity
      of human anti-Ids to modulate the release of histamine was examined in an in
      vitro system of human basophil degranulation. Anti-Ids were prepared from the
      serum of six Dermatophagoides pteronyssinus (Dp)-hypersensitive patients
      suffering from atopic dermatitis and who had never been desensitized. Basophils
      were obtained from the blood of atopic donors. The extent of histamine release
      was determined using a fluorometric assay. RESULTS: We show that: anti-Ids
      trigger the release of histamine in an allergen-specific, dose- and IgE-dependent
      manner; the release is not due to the presence of allergen and/or anti-IgE
      antibodies; and that the degranulating activity can be removed by absorption with
      affinity-purified anti-Dp antibodies of the corresponding patient. CONCLUSION:
      These results indicate that spontaneously produced human anti-Ids can modulate
      the reactivity of human basophils.

PMID- 8556565
TI  - Exudative hyperresponsiveness of the airway microcirculation in seasonal allergic
      rhinitis.
AB  - BACKGROUND: Mucosal exudation of plasma is a non-injurious, physiological
      response of the airway microcirculation to different inflammatory processes. The
      exudative response is similar in the nose and bronchi and exudation occurs in
      both allergic asthma and rhinitis. The exudative response is a specific end-organ
      function of the mucosal microcirculation that may be altered in airway diseases.
      OBJECTIVE: This study examines the hypothesis of altered responsiveness of the
      superficial airway microcirculation to vascular permeability-increasing
      challenges in sustained allergic inflammation. METHODS: Fourteen patients with
      birch-pollen induced allergic rhinitis were studied for 7 weeks during a Swedish
      birch-pollen season. Nasal symptoms (itching, sneezing, blockage, and discharge)
      were recorded and the occurrence of pollen was determined. The plasma exudation
      response was examined by topical histamine challenges at the end (May) and well
      out of (December) the season. Challenge and lavage were carried out concomitantly
      using a 'nasal pool'-device. The unilateral nasal cavity was filled for
      consecutive 10 minute periods with saline and two concentrations of histamine (80
      micrograms/mL and 400 micrograms/mL). The lavage fluid levels of different-sized
      plasma proteins (albumin-66,000 D, fibrinogen-340,000 D, and alpha 2
      macroglobulin-725,000 D) were determined. RESULTS: The pollen season was mild
      resulting in only minor nasal symptoms. Histamine produced exudation of all
      plasma proteins across the microvascular epithelial barriers with particularly
      strong correlation between the levels of albumin and alpha 2-macroglobulin (r =
      0.98; P < 0.001). The exudative response to histamine was concentration-dependent
      (P < 0.05) and, furthermore, it was significantly greater late into the season
      compared with outside the pollen season (albumin: P < 0.05, fibrinogen; P < 0.05,
      alpha 2-macroglobulin: P < 0.01). CONCLUSION: We conclude that histamine produced
      concentration-dependent nasal airway exudation of bulk plasma in subjects with
      seasonal rhinitis and that this response is abnormally great during the pollen
      season. Whether angiogenesis or increased responsiveness of the microvascular
      endothelium may explain this phenomenon now remains unknown. We suggest that a
      microvascular exudative hyperresponsiveness may characterize allergic airway
      disease.

PMID- 8556566
TI  - Comparison of the effects of salmeterol and salbutamol on clinical activity and
      eosinophil cationic protein serum levels during the pollen season in atopic
      asthmatics.
AB  - BACKGROUND: In atopic asthma there is strong evidence of eosinophils playing an
      active role in pathogenesis. Some investigations demonstrated that eosinophil
      cationic protein (ECP) serum levels increased in atopic patients with asthma
      during pollen season. OBJECTIVE: The aim of the study was to evaluate the effects
      of short-term (1 week) beta 2-agonist treatment on lung function and eosinophil
      activity in asthmatic patients. METHODS: We used an open, randomized, cross-over
      design to compare the effects of salbutamol (200 micrograms q.i.d.) and
      salmeterol (50 micrograms b.i.d.) on peak expiratory flow rate (PEFR), blood
      eosinophil count and serum levels of ECP as a measure of eosinophil activity in
      20 mild atopic asthmatics. RESULTS: Morning and evening PEFR values were both
      significantly higher during salmeterol treatment than during the salbutamol
      period. Conversely, both morning and evening daily asthma symptom scores were
      significantly lower during salmeterol treatment compared with those recorded
      during the salbutamol period. The mean basal eosinophil blood count on salmeterol
      treatment (601 +/- 189 mm3) was not higher than the mean count on salbutamol
      treatment (612 +/- 204 mm3). After both treatments the mean eosinophil blood
      counts were unchanged (619 +/- 189 mm3 and 576 +/- 212 mm3, respectively). No
      significant differences in blood eosinophil counts were observed between or
      within treatments at any time. No significant difference was observed in baseline
      mean ECP serum concentration (43.8 +/- 26.3 micrograms/L on salmeterol treatment
      and 41.7 +/- 29.8 micrograms/L on salbutamol treatment, respectively). After
      salmeterol treatment the mean ECP serum concentration had fallen significantly to
      20.9 +/- 18.6 micrograms/L (P < 0.01), whereas after salbutamol treatment it was
      unchanged (42.0 +/- 25.1 micrograms/L). Salmeterol treatment produced a decrease
      in ECP serum levels without any changes in blood eosinophil count. CONCLUSION:
      This study demonstrates that salmeterol affords a significant improvement in
      asthma control during the pollen season, measured by both subjective and
      objective parameters, compared with salbutamol. This greater efficacy may be
      related to inhibition of eosinophil degranulation during the pollen season.

PMID- 8556567
TI  - The lack of effect of benzalkonium chloride on the cilia of the nasal mucosa in
      patients with perennial allergic rhinitis: a combined functional, light, scanning
      and transmission electron microscopy study.
AB  - BACKGROUND: Controversy still exists about the effect of 0.02% benzalkonium
      chloride (BKC), a preservative in many nasal sprays, on human nasal epithelium in
      vivo. OBJECTIVE: To determine the safety of BKC by assessing its effect on the
      function and morphology of cilia of human nasal epithelium. METHODS: A single
      centre, double-blind nasal biopsy study in 22 patients with perennial allergic
      rhinitis, receiving fluticasone propionate aqueous nasal spray (FPANS) containing
      BKC, BKC plus placebo or placebo alone for 6 weeks. Before, at two weekly
      intervals during treatment and 2 weeks after treatment ceased an indigocarmine
      saccharine transport time (ICST) was performed. RESULTS: ICST results did not
      significantly vary between the groups. There was no statistical relationship
      between the number of ciliated cells present and the treatment the patients
      received. Scanning and transmission electron microscopy examination showed no
      effects of BKC. CONCLUSION: Despite reports of its ciliostatic effects in vitro,
      BKC did not have such an effect when it was applied for 6 weeks (with/without
      fluticasone propionate) to the nasal mucosa of perennial allergic rhinitis
      patients in vivo.

PMID- 8556568
TI  - Effect of intranasal fluticasone proprionate on the immediate and late allergic
      reaction and nasal hyperreactivity in patients with a house dust mite allergy.
AB  - BACKGROUND: Patients with perennial allergic rhinitis develop nasal symptoms not
      only after allergen exposure, but generally also after non-specific stimuli.
      OBJECTIVE: To evaluate the effect of 2 week's treatment with fluticasone
      propionate aqueous nasal spray (FPANS) on the nasal clinical response,
      inflammatory mediators and nasal hyperreactivity. METHODS: Twenty-four rhinitis
      patients allergic to house dust mite (HDM), participated in a double-blind,
      placebo-controlled crossover study. After 2 week's treatment with placebo or 200
      micrograms FPANS twice daily, patients were challenged with HDM extract. Symptoms
      were recorded and nasal lavages were collected for up to 9.5 h after challenge.
      Nasal hyperreactivity was determined by histamine challenge 24 h later. RESULTS:
      Because of a carry-over effect for the immediate symptom score, for this variable
      only the data from the first treatment period were used. FPANS treatment resulted
      in a significant decrease of nasal symptoms with 70%, 69% and 63% after 100, 1000
      and 10,000 Biological Units (BU)/mL of HDM extract respectively. Active treatment
      resulted in a 76% decrease of the late-phase symptoms. FPANS treatment
      significantly reduced albumin influx after HDM 1000 BU/mL with 62% and tended to
      reduce tryptase release after HDM 1000 BU/mL (P = 0.0629). During the late phase
      FPANS treatment reduced albumin influx with 67% and eosinophil cationic protein
      (ECP) release with 83%. No effect of FPANS was seen on histamine levels. FPANS
      significantly decreased histamine-induced symptom score with 34%, secretion with
      32% and sneezes with 41%. CONCLUSION: FPANS significantly inhibits the immediate
      and late allergic response, and nasal hyperreactivity, probably by suppressing
      mast cells and eosinophils in the nasal mucosa.

PMID- 8556569
TI  - Antihistamine activity, central nervous system and cardiovascular profiles of
      histamine H1 antagonists: comparative studies with loratadine, terfenadine and
      sedating antihistamines in guinea-pigs.
AB  - BACKGROUND: Sedation limits the clinical utility of classical H1 antihistamines,
      while newer antihistamines such as loratadine and terfenadine are non-sedating.
      However, clinical use of the terfenadine has been associated with rare but severe
      cardiac arrhythmias, in particular torsades de pointes. OBJECTIVE: To establish a
      quantitative experimental model for assessing the sedating and cardiotoxicity
      potential of non-sedating and sedating antihistamines. METHODS: Drugs were
      administered intravenously and the integrated amplitude of the cortical
      electroencephalogram (EEG) signal was recorded. The threshold dose that depressed
      EEG activity was compared with the dose required to inhibit by 50% the peripheral
      bronchospasm elicited by 10 micrograms/kg i.v., of histamine. In separate
      studies, the electrocardiogram (ECG) and cardiovascular effects of loratadine (30
      and 100 mg/kg, i.v.), terfenadine (10 mg/kg, i.v.), promethazine (5 mg/kg, i.v.)
      and diphenhydramine (20 mg/kg, i.v.) were evaluated. RESULTS: The sedating
      antihistamines, diphenhydramine and promethazine, depressed the integrated EEG at
      doses between 0.6 and 2.0 times their peripheral antihistamine doses. Loratadine
      had no EEG depressant activity at 100 mg/kg, i.v., a dose more than 170 times its
      ED50 (0.58 mg/kg, i.v.) against histamine bronchospasm. We were unable to
      evaluate the EEG effects of terfenadine, because it produced cardiovascular
      collapse at 10 mg/kg, i.v. Loratadine and promethazine did not produce adverse
      cardiovascular effects, nor did they alter normal ECG activity. Diphenhydramine
      produced bradycardia followed by a transient hypertensive phase without affecting
      the QTc interval. In contrast, terfenadine elicited hypotension, bradycardia and
      significant arrhythmogenic activity, causing a prolongation of the QTc interval
      and a torsades de pointes--like ventricular arrhythmia. Pharmacokinetic studies
      after i.v. administration of loratadine (30 and 100 mg/kg) demonstrated plasma
      levels of loratadine and its major metabolite descarboethoxyloratadine to be
      several orders of magnitude greater than levels found in humans at the clinical
      dose of 10 mg. CONCLUSION: The CNS depressant effects of H1 antihistamines are
      promethazine approximately diphenhydramine >> loratadine = placebo. Of the non
      sedating antihistamines, loratadine was devoid of adverse cardiovascular effects
      whereas terfenadine caused a pronounced disruption of the normal ECG,
      characterized by a torsades de pointes-like effect.

PMID- 8556570
TI  - Evaluation of the allergic/irritant potential of air pollutants: detection of
      proteins modified by volatile organic compounds from oilseed rape (Brassica napus
      ssp. oleifera) using electrospray ionization-mass spectrometry.
AB  - BACKGROUND: Upward trends in allergy and asthma rates have been reported in most
      western societies, including the UK, where around 15-20% of the population now
      suffer from allergy or asthma. Scientific proof of the causes of these increases
      relies on accurate assessment of exposure and standardized diagnostic tests, such
      as for specific IgE in blood serum and skin testing. For many air pollutants it
      has proven difficult to assess an individual's exposure outside an occupational
      environment and reliable test development is hampered by not knowing whether an
      allergic or irritant mechanism is involved. These problems are particularly
      evident in the controversial issue of whether airborne releases from oilseed rape
      can cause health effects. OBJECTIVE: To develop a method for evaluating the
      allergic/irritant potential of air pollutants and to assess whether the volatile
      organic compounds emitted by oilseed rape have this potential. METHODS: Proteins
      were exposed in vitro to volatile organic compounds emitted by oilseed rape.
      Electrospray ionization-mass spectrometry was used to detect any resultant
      protein modifications. RESULTS: Dimethyl disulphide, thiocyanic acid methyl ester
      and 2-methyl-propanenitrile were able to modify human proteins. In addition, two
      isothiocyanates which can be emitted by damaged oilseed rape also have this
      ability. The major products emitted by undamaged oilseed rape, terpenes, a
      sesquiterpene and a terpene alcohol did not have this property, but the possible
      role of their oxidized products is discussed. CONCLUSION: Some of the volatile
      organic compounds emitted by oilseed rape have the potential to be
      allergens/irritants. Standardized modified proteins produced by this method
      should prove useful for biomonitoring human exposure in molecular epidemiological
      studies as well as in diagnostic tests. This method should find further
      application in investigations into the possible health effects of other
      environmental pollutants.

PMID- 8556571
TI  - Quantitation of the major allergen of several Parietaria pollens by an anti-Par 1
      monoclonal antibody-based ELISA. Analysis of crossreactivity among purified Par j
      1, Par o 1 and Par m 1 allergens.
AB  - BACKGROUND: Plants of the genus Parietaria, Urticaceae family, represent a major
      cause of pollinosis in the Mediterranean area. Different Parietaria species
      crossreact to a great extent, but studies on the crossreactivity among the major
      allergens of these pollens have not been carried out so far. OBJECTIVE: To
      develop an immunochemical method to quantify the major Parietaria judaica
      allergen, Par j 1, as well as to verify the presence of Par j 1-like proteins in
      different Urticaceae pollens. These proteins would be purified in order to study
      the cross-reactivity among them. METHODS: Immunoaffinity chromatography with a
      monoclonal antibody, solid-phase enzyme-linked immunoassays and SDS-PAGE.
      RESULTS: A monoclonal antibody-based ELISA for the quantification of Par j 1 has
      been developed. The assay has a sensitivity of 0.2 ng/mL and shows a high
      correlation with the allergenic activity of P. judaica extracts determined by
      radioallergosorbent assay (RAST) inhibition. By means of this assay, proteins
      homologous to Par j 1 were detected in P. officinalis and P. mauritanica. These
      proteins (Par o 1 and Par m 1, respectively) were purified by affinity
      chromatography using the same monoclonal antibody employed in the ELISA. Crossed
      inhibition experiments demonstrated that Par j 1, Par o 1, and Par m 1, competed
      for the binding of specific IgE from a P. judaica-sensitive patients serum pool.
      CONCLUSION: The results here described suggest that shared allergenic epitopes
      are present in the three main allergens investigated, which may simplify the
      diagnosis and therapy for Parietaria allergy.

PMID- 8556572
TI  - Prediction of histopathologic features and proliferative activity of uterine
      leiomyoma by magnetic resonance imaging prior to GnRH analogue therapy:
      correlation between T2-weighted images and effect of GnRH analogue.
AB  - To predict the histological features and proliferative activity of leiomyomas and
      to evaluate the effect of GnRH analogues (GnRHa) by MR images, the correlation
      between MR images and histopathologic findings was studied on 137 leiomyomatous
      nodules from 79 patients. The correlation among cellularity, proliferative
      activity and MR images was studied on sections of 42 leiomyomatous, nodules
      stained with hematoxylin-eosin and immunohistochemistry for proliferating cell
      nuclear antigen. The utility of MR imaging in assessing response to therapy with
      a GnRHa (buserelin 900 micrograms/day, intranasal for 16 weeks) was studied on 62
      leiomyomatous nodules from 29 patients. On T2-weighted MR images, we encountered
      five major images. According to the increase of signal intensity relative to that
      of the myometrium and/or the endometrium, the images were classified as Type 1,
      Type 2, Type 3, Type 4, and Type 5. Histopathologically, the majority of Type 1,
      Type 2 and Type 3 images had features of typical leiomyoma. Almost all cellular
      leiomyomas and bizarre leiomyomas had Type 4 images. Variable degenerative
      features were observed in the nodules with Type 5 images. According to the
      increase of signal intensity, leiomyomas had a tendency to show a high degree of
      both cellularity and proliferative activity. Moreover, the reduction rate of
      leiomyomatous nodules after GnRHa therapy correlated with the tumor signal
      intensity on T2-weighted images before therapy. The reduction rate was the lowest
      in Type 1 images (20.9%) and the highest in Type 4 images (50.7%). These results
      suggest that increased the signal intensity on T2-weighted MR images correlates
      with the cellularity and proliferative activity of leiomyomas, and with tumor
      response to GnRHa treatment. MR imaging enables quantitative monitoring of GnRHa
      therapy in patients with leiomyomatous nodules, and allows us to predict the
      histopathology, cellularity, proliferative activity, and shrinkage rate of
      nodules before GnRHa treatment.

PMID- 8556573
TI  - Laparoscopic assisted vaginal hysterectomy: an audit plus a word of caution.
AB  - Laparoscopic assisted vaginal hysterectomy (LAVH) performed in 109 cases has been
      reviewed. In this series the mean operative time was 89 minutes and mean
      inpatient hospitalization was 3.7 days. Throughout the review, 6 patients were
      considered to have major complications and each is discussed. The association of
      previous caesarean section and bladder damage is noted. LAVH widens the
      indications available for vaginal hysterectomy in younger women in whom the
      abdominal approach would previously be indicated, but extra caution is advised
      when this technique is first introduced to a gynaecological service.

PMID- 8556574
TI  - External cephalic version from 34 weeks under tocolysis: factors influencing
      success.
AB  - External cephalic version (ECV) was performed on 72 patients from 34 weeks of
      gestation under tocolysis, with ultrasound control and cardiotocograph
      surveillance. Successful ECV was associated with multiparity, decreased lower
      segment caesarean section (LSCS) rate, and earlier discharge home. ECV was
      successful in 51.4% of patients overall, with the success rate being 35% in
      primigravidas and 71.4% in multiparas (p < 0.005). The LSCS rate was reduced from
      91.4% to 0% (p < 0.0001) on comparing the unsuccessful and the successful ECV
      groups, while breech presentation was reduced from 94.3% to 0% (p < 0.0001).
      There were no significant fetal complications.

PMID- 8556575
TI  - Use of bromodeoxyuridine, proliferating cell nuclear antigen, and nucleolar
      organizer regions in the multiparametric assessment of proliferating potency in
      cervical intraepithelial neoplasia.
AB  - The authors analysed of the proliferative activity of intraepithelial neoplasia
      of the cervix utilizing the labeling index of monoclonal antibody to
      Bromodeoxyuridine (BrdU) or proliferating cell nuclear antigen (PCNA), and the
      number of Nucleolar organizer regions (Ag-NOR). The BrdU labeling index (B.L.I.)
      for normal squamous epithelium, mild dysplasia, and moderate dysplasia were
      significantly lower than for severe dysplasia or carcinoma in situ. The PCNA
      labeling index (P.L.I.) for normal squamous epithelium, mild dysplasia, and
      moderate dysplasia were significantly lower than for severe dysplasia or
      carcinoma in situ. The number of Ag-NOR dots of normal squamous epithelium and
      mild dysplasia were lower than those of severe dysplasia or carcinoma in situ.
      There are significantly positive correlations of the B.L.I., P.L.I., and the
      number of Ag-NORs in cervical intraepithelial neoplasia.

PMID- 8556576
TI  - Toxoplasmosis as a cause of repeated abortion.
AB  - The extent to which toxoplasmosis causes habitual abortion is still
      controversial. The present study was carried out on 100 cases of repeated
      abortions, and 40 multiparous pregnant women at 20th week gestation as a control.
      Tests for the presence of toxoplasma IgG and/or IgM antibodies were done for both
      groups. It was found that 19% of the selected cases, and 7.5% of the control were
      seropositive for IgM. The difference was statistically insignificant, therefore
      acute toxoplasmosis, most probably, is not related to habitual abortions, whereas
      37% of the selected cases and only 10% of the control group were seropositive at
      high dilution for IgG antibody, this statistical significant difference indicates
      that chronic toxoplasmosis, most probably is a significant cause of repeated
      abortion. Also it has been found that toxoplasmosis has a significant relation to
      abortion at first trimester.

PMID- 8556577
TI  - Urokinase-type plasminogen activator (uPA) and its receptor (CD87): a new target
      in tumor invasion and metastasis.
AB  - Extravasation and intravasation of tumor cells in solid malignant tumors is
      controlled by 3 steps: 1) attachment to and interaction of tumor cells with
      components of the basement membrane and the extracellular matrix, 2) local
      proteolysis, and 3) tumor cell migration. Evidence has accumulated that different
      types of tumor-associated proteases, their inhibitors and receptors are involved
      in tumor invasion and metastasis. Four different classes of proteases are known
      to be correlated with the malignant phenotype: 1) Matrix metalloproteases;
      including collagenases, gelatinases and stromelysins. 2) Cysteine proteases;
      including cathepsins B and L. 3) Aspartyl protease cathepsin D. 4) Serine
      proteases; including plasmin and tissue-type plasminogen activator (tPA) and
      urokinase-type plasminogen activator (uPA). A strong independent prognostic value
      (relapse-free and/or overall survival) has especially been demonstrated for uPA
      and its inhibitor PAI-1 in patients with cancer of the breast, ovary, stomach,
      esophagus, colon, lung, and kidney thus predicting the course of the cancer
      disease. The strong correlation between elevated uPA and/or PAI-1 values in
      primary cancer tissues and the malignant phenotype of cancer cells has prompted
      to explore new tumor biology-oriented concepts in order to suppress uPA or uPA
      receptor (CD87) expression or to abrogate interaction of uPA with CD87. Various
      very different approaches to interfere with the expression or reactivity of uPA
      or CD87 at the gene or protein level were successfully tested including antisense
      oligonucleotides, antibodies, inhibitors and recombinant or synthetic uPA and
      CD87 analogues.

PMID- 8556578
TI  - EGF-R and overexpression of the oncogene c-erbB-2 in ovarian cancer:
      immunohistochemical findings and prognostic value.
AB  - PURPOSE: The purpose of this study was to investigate the prognostic value of EGF
      R (c-erbB-1) compared to the overexpression of the c-erbB-2 oncogene product p185
      in ovarian cancer. PATIENTS AND METHODS: The study was conducted on 266
      previously untreated ovarian cancer patients with FIGO stage I-IV disease. EGF-R
      and c-erbB-2 oncogene product p185 have been evaluated using
      immunohistochemistry. Survival times were analyzed according to the method
      described by Kaplan and Meier. For the simultaneous evaluation of the prognostic
      relevance of the analyzed factors, a Cox proportional hazards regression was
      performed. RESULTS: EGF-R was detected in 13%, and c-erbB-2 oncogene product p185
      in 18% of primary tumors. EGF-R showed no significant impact on the survival
      time, whereas c-erbB-2 oncogene product p185 positive patients had a
      significantly worse prognosis compared to p185 negative cases (p = 0.002). In the
      multivariate analysis, c-erbB-2 oncogene product p185, like tumor stage,
      histological grade and age, was found to be a significant prognostic factor.
      CONCLUSION: These data confirm the prognostic importance of the c-erbB-2;
      oncogene product p185 in ovarian cancer at the time of primary surgery, while EGF
      R does not seem to have prognostic relevance.

PMID- 8556579
TI  - The vaginal radical operation of cervical cancer.
AB  - Choosing the surgical technique for the cervix carcinoma--vaginal or abdominal-
      it is particularly necessary to take into account the lymphatic spread of the
      cervix. As it is not possible to realize a lymphadenectomy in a vaginal
      procedure, it has to be found a preoperative diagnostic method which enables very
      surely the exclusion of lymph node involvement. In summary of the facts stated up
      to now, one can conclude as follows: 1. The FIGO-classification is too
      subjective. 2. There is a significant correlation between tumor volume and lymph
      node involvement. 3. The tumor markers--as e.g. PCNA, p53, c-neu, EGF, beta 1
      Integrin etc.--show no correlation with the lymph node involvement. 4. Only MRI
      allows an exact preoperative measurement of the tumor volume. 5. On account of
      the above mentioned results, it seems to be possible to extend the indication for
      the vaginal radical surgery on cases with a small tumor volume.

PMID- 8556580
TI  - Biochemical events in cervical ripening dilatation during pregnancy and
      parturition.
AB  - In specimens taken from the posterior lip of the cervix uteri we determined the
      collagenase activity and the glycosaminoglycan concentration. In biopsies
      obtained from the lower uterine segment during cesarian section we measured
      cytokines (IL-8, IL-2, TNF alpha) and matrix metalloproteinases (MMP-8, MMP-9).
      We found that the release of collagenases is critically involved in the process
      of cervical dilatation. The glycosaminoglycan concentration increases during
      pregnancy and shows remarkable changes of the distribution patterns of the
      different glycosaminoglycans. The parturition is characterized by a dramatic loss
      of most of the glycosaminoglycans. Furthermore, the IL-8 shows a close
      correlation to the clinical feature of cervical ripening and is closely
      associated with the release of MMP-8 and MMP-9. Summarizing the process of
      cervical maturation and dilatation is a complex enzymatic controlled process with
      substantial remodelling of the cervical extracellular matrix. The cytokines IL-8
      seems to play an essential role in triggering the process of cervical dilatation.

PMID- 8556581
TI  - The prevention of mechanical birth trauma by means of computer aided simulation
      of delivery by means of nuclear magnetic resonance imaging and finite element
      analysis.
AB  - Anatomic disproportion gains an increasing interest in obstetrics. Imaging
      procedures (radiologic pelvimetry, computed or magnetic resonance imaging (MRI)
      fail to reflect the dynamics of delivery including deformations of the birth
      channel as well as of fetal structures. To validate findings of imaging
      procedures in this respect a method has been developed to perform a dynamic,
      biomechanical postprocessing of the static informations obtained from MRI. Using
      an especially developed software MRI pixel matrices of maternal pelvis and fetal
      head were color-codef1p4d--according to the principle of same density--line data
      were created. After sectional attribution of the resulting polygones a three
      dimensional mesh of so called Finite elements (FE) was created, which then can be
      used for deformation analysis. Fetal head was then moved through the birth
      channel by means of computed simulation. This allows not only ongoing
      deformations to be visualized but also resulting forces to be calculated for at
      any time of the delivery process for any point of the anatomical model.
      Performing these simulations assuming various anatomic and physiologic conditions
      an obstetrical-biomechanical data basis could be obtained, that was implemented
      in a PC-based expert system. This allows interpretation of pelvimetric data with
      regard to birth dynamics.

PMID- 8556582
TI  - Perinatal database in Germany.
AB  - By collecting standardized data from up to 600,000 deliveries per year in Germany
      a nation-wide database has been established in recent years enabling not only
      regional and overregional quality control, but also the scientific analysis of
      rare maternal and fetal complication. During the observation period of 10 years
      the understanding of perinatal risk factors has considerably improved and the
      perinatal mortality has declined from 9.4 to 6.4 (per 1,000 deliveries). From the
      huge amount of calculations typical results are presented.

PMID- 8556583
TI  - [Approach to the diagnosis and therapy of vascular neuropathy].
AB  - Peripheral neuropathy is a very common clinical manifestation of vasculitis
      syndromes which may present as an early sign of such neuropathy or else may be
      the only such sign as in the case of non-systemic vascular neuropathy. The
      clinical affectation of the neuropathy depends on the extent and course of the
      ischaemic changes brought on by vasculitis, with multineuritis being the most
      usual presenting form of vascular neuropathy. Neurophysiological studies show the
      extent and severity of the neuropathy and often identify subclinical affectation
      representing a mixed pattern of affectation with axomal predominance. Nerve
      biopsy is a prerequisite for diagnosis, noting any infiltration by inflammatory
      cells and/or necrosis at perivascular and transmural levels together with vessel
      thrombosis or rechanneling. Using immunofluorescent techniques, immune deposits
      of IgG, IgM and components may be noted. Vasculitis neuropathy treatment is
      fundamentally carried out at the expense of corticosteroids and immunosuppressive
      which may be administered individually or in combination. In vasculitis
      neuropathy bad prognostic factors would include old age, the presence of kidney
      disease and delayed diagnosis and treatment.

PMID- 8556584
TI  - A neurologist's reflections on boxing. IV. Late and permanent brain damage.

PMID- 8556585
TI  - A neurologist's reflections on boxing. V. Conclude remarks.
AB  - Clinical and morphological publications have shown convincingly, that
      participation in boxing leads to a severe permanent brain damage. The extent of
      the brain damage is correlated to the number of bouts fought, which
      correspondents in a certain way how many blows against his head a boxer received
      and to his weight class. The intensity of a boxing blow of a heavyweight is much
      more severe than those achieved by boxers of lighter weight classes. The
      permanent brain damage in a boxer, the amateur and the professional boxer,
      manifests itself in several clinical syndromes in which the pyramidal, the
      extrapyramidal and the cerebellar systems are involved. A traumatic Parkinsonism,
      in its complete or abortive form, develops as the result of the numerous boxing
      blows a boxer sustains in his boxing career. Especially lateral parts of the
      substantia nigra are affected and reveal at macroscopical and microscopical
      examination a severe loss of pigmented neurons. Melanin pigment is visible free
      in the tissue and/or is phagozytosed in macrophages and glial cells. The
      traumatic Parkinson syndrome, often only in an abortive form, is combined in a
      boxer with additional clinical and morphological findings due to traumatic
      lesions in other areas of the brain. It is not as pure as in a patient with a
      Parkinson syndrome sui generis. The permanent brain damage in a boxer is diffuse,
      involving all areas of the brain. Especially involved are the large neurons of
      different layers of the cerebral cortex, the neurons of the Ammons horn
      formation, the Purkinje cells of the cerebellum. In place of destroyed and lost
      neurons, proliferation of glial elements, especially astroglial cells, has
      occurred. The defects are first replaced by protoplasmatic astroglial elements,
      and later by fibrillary astroglia. The destroyed neurons are replaced by glial
      scar tissue, which cannot perform the functions of the lost neurons. It is a
      process which is called partial necrosis of brain tissue. There is no reparation
      or restitution of the destroyed neural tissue of the brain. What is destroyed
      remains so, a restitution ad integrum does not occur. As the result of the
      diffuse loss of neurons in the brain a cerebral atrophy exists. The septum
      pellucidum, which consists of two thin lamellae, and is small or very small in a
      normal brain, forms a Cavum septi pellucidi, which is considerably enlarged. The
      walls of this structure, especially in its dorsal parts are considerably thinned;
      they show fenestrations and are, in dorsal parts no longer detectable, so that a
      direct connection between the two lateral ventricles exists. The clinically and
      morphologically existing permanent brain damage is the result of the boxing
      activity. Diagnostically, processes of another origin, such as alcoholism, luetic
      processes, other forms of dementia, etc. can undoubtedly be excluded. A permanent
      brain damage develops in professional and amateur boxers. The objection, which
      are voiced by members of the different Amateur Boxing Association, that such
      permanent brain damage in amateur boxers today no longer exists, after stricter
      protective measurements were introduced, is not tenable. Individuals who
      represent today the opinion, that a permanent brain damage or punch drunkenness
      in boxers does not occur, are not familiar with the pertinent medical literature.
      The argument, the injury quotient in boxing is lower than in all other athletic
      activities is not sound, since the statistics show only the inconsequential
      injuries of boxers, as lesions of the skin of the face, injuries of the hand,
      fractures, etc. but not the much more important and severe permanent brain
      damage, which is not taken into consideration in these so-called statistics.
      Besides of the permanent brain damage of former boxers as the result of the
      repeated and numerous blows against their head, severe permanent damage of the
      eyes and the hearing organ exists.

PMID- 8556586
TI  - [Liver transplantation and neurological complications of hepatopathy].

PMID- 8556587
TI  - [Neurological complications after liver transplantation].

PMID- 8556588
TI  - [Cerebellar hypoplasia in the newborn: association with respiratory control
      disorders and mental retardation].
AB  - Cerebellum malformations are frequently diagnosed since the advent of the
      neuroradiological studies (computed tomography, magnetic resonance imaging and
      ultrasonography). Cerebellar hypoplasia is found in association with a wide
      variety of neurologic and systemic disorders. Clinical picture in newborn may be
      different than in other periods of life. Two characteristics are interesting in
      neonatal period: their relation with abnormal respiratory control and mental
      retardation. The pathophysiology of cerebellar hypoplasia is uncertain, however
      experimental studies suggest than an abnormality of the Bergman glia may lead to
      the observed granulle cell layer deficiency in this malformation. It is tempting
      to speculate that a similar migrational abnormality in the cerebrum accounts for
      the intellectual impairment seen in some affected patients. Respiration is a
      complex neural function requiring precise coordination of numerous neural
      circuits. Cerebellar hypoplasia may be important in the pathogenetic mechanism of
      abnormal respiratory control due to cerebellar respiratory control disturbance.
      Also diaphragmatic dysfunction may occur in association with cerebellar atrophy.
      We report two newborns with cerebellar hypoplasia (vermis and hemispheres)
      associated with central respiratory and neurological dysfunction, and mental
      retardation.

PMID- 8556589
TI  - [Verbal auditory agnosia: SPECT study of the brain].
AB  - Verbal auditory agnosia are rare in clinical practice. Clinically, it
      characterized by impairment of comprehension and repetition of speech but
      reading, writing, and spontaneous speech are preserved. So it is distinguished
      from generalized auditory agnosia by the preserved ability to recognize non
      verbal sounds. We present the clinical picture of a forty-years-old, right handed
      woman who developed verbal auditory agnosic after an bilateral temporal ischemic
      infarcts due to atrial fibrillation by dilated cardiomyopathie.
      Neurophysiological studies by pure tone threshold audiometry: brainstem auditory
      evoked potentials and cortical auditory evoked potentials showed sparing of
      peripheral hearing and intact auditory pathway in brainstem but impaired cortical
      responses. Cranial CT-SCAN revealed two large hypodenses area involving both
      cortico-subcortical temporal lobes. Cerebral SPECT using 99mTc-HMPAO as
      radiotracer showed hypoperfusion just posterior in both frontal lobes nect to
      Roland's fissure and at level of bitemporal lobes just anterior to Sylvian's
      fissure.

PMID- 8556590
TI  - [Increased level of Gerstmann's syndrome secondary to thalamic hematoma].
AB  - A patient developed enlarged Gerstmann syndrome after left thalamic haematoma.
      Single photon emission computerised tomography (SPECT) showed left parietal
      temporal cortical hypocapture. These findings would lead us to believe that the
      clinical picture of our patient was due to a thalamic-cortical diaschitic
      phenomenon.

PMID- 8556591
TI  - [Chronic demyelinating polyneuropathy associated with multiple sclerosis: a
      patient with two diseases].
AB  - We studied the clinical, paraclinical and laboratory findings of a patient
      suffering from multiple sclerosis (MS) with chronic demyelinating polyneuropathy.
      As well as being a new case of demyelination of the central and peripheral
      nervous system not normally associated with the presence of antiganglionic
      antibodies, our patient presented clinical signs distinct from each disease with
      the characteristic abnormalities of cerebrospinal fluid (CSF) (cytological
      albumin dissociation at the moment when an outbreak appeared at the peripheral
      level and an increase in intrathecal secretion when the outbreak was at the
      central nervous system level). Demyelinating diseases of the central and
      peripheral nervous systems are a field of great interest in trying to find the
      antigenic bull's eye for MS.

PMID- 8556592
TI  - [Biopercular lesion with inverse dissociation].
AB  - Foix-Chavany-Marie Syndrome or anterior opercular syndrome constitutes the
      cortical form of pseudobulbar palsy. Its most common etiology is stroke in the
      region of either operculum. Clinically it can be characterized by severe
      dysarthria and facio-pharyngo-glosso-masticatory dysplasia with automatic
      voluntary dissociation. An inversion of this classical dissociation can be seen
      in patients with emotional paralysis in the face, in whom asymmetry of emotional
      expression but conservation of voluntary movement can be seen. The lesional
      topography of this inverse dissociation corresponds to the supplementary motor
      area. both processes support the existence of an anatomical base which is
      different for emotional movements and voluntary types. We describe the clinical
      case of a 65 year old woman with a history of breast cancer who presented a
      subacute and progressive clinical picture of dysphagia and severe dysarthria.
      Upon neurological examination slight velo-palato-pharyngea was noticed; most
      relevant was paralysis of the facial muscles for either emotional or automatic
      movements while voluntary innervation was maintained. Neuroradiological studies
      show the presence of brain metastasis located in both Roland opercula. Although
      the neuroanatomic bases for automatic-voluntary dissociation remain unclear, our
      case lends weight to the evidence that impulses for voluntary and emotional
      movements originate in different cortical areas or else take a different route
      through the brain. We have been unable to find any cases of biopercular lesion
      with inverse dissociation described in the literature we reviewed.

PMID- 8556593
TI  - [Thyroid ophthalmopathy ad a unique clinical manifestation of thyrotoxicosis].
AB  - Thyroid ophthalmopathy (TO) or Graves ophthalmopathy embraces a broad range of
      eye abnormalities which up to 90% of patients with hyperthyroidism (HT) are
      affected with. In some 10% of TO patients, this may begin oligosymptomatically,
      often with double vision and with neither clinical nor biochemical signs of
      thyroid disease. It is imperative to carry out a differential diagnosis with
      countless other causes for double vision and other eye socket processes.
      Ophthalmopathy may also occur in patients with hypothyroidism and for this reason
      some authors prefer to refer to it as dysthyroid orbitopathy. We present four
      cases of TO in which double vision was the first clinical sign of TO which in one
      case became severe, in two cases preceded hyperthyroid symptomatology and in the
      remaining case happened after hyperthyroidism had been corrected. The most
      valuable diagnostic test was orbit computerised tomography (CT) scan, which
      proved positive in all cases, and that, along with clinical tests and thyroid
      function data, confirmed a diagnosis of TO. All initially improved with
      corticosteroids although none completely regained eye movement during the time
      they were under supervision. The same happens in about 50% of patients who do not
      respond to treatment either with corticosteroids or with radiotherapy, and
      response is usually incomplete in those who do so respond.

PMID- 8556594
TI  - [CNS vasculitis after ophthalmic herpes zoster infection].
AB  - We present a case of cerebral vasculitis secondary to infection with Varicella
      Zoster Virus which appeared in a 27 year old patient after a latency period of
      eight weeks. We emphasize the usefulness of angioresonance as a fitting means of
      evolutive follow up without the need to carry out control cerebral angiography.
      We likewise point out the usefulness of acyclovir as the sole treatment necessary
      in non-complicated cases.

PMID- 8556596
TI  - [Incidence of cerebrovascular disease in Spain: a study in a rural area of
      Girona].
AB  - In Spain in recent years several studies have been carried out into the incidence
      of acute stroke among the population at large. The average figure for incidence
      in these studies was 227 cases per 100,000 inhabitants, ranging from a low of 163
      to a high of 323 cases. In the study made among the rural population of Girona
      the incidence rate was 257 cases per 100,000 inhabitants which was reduced to 134
      cases when adjustment was made with world population. The overall incidence rate
      for stroke was 193 cases per 100,000 inhabitants, with that for first stroke
      being 174 cases per 100,000 inhabitants. The incidence of Transient Ischaemic
      Attacks (TIA) was 64 cases per 100,000 inhabitants. Acute stroke incidence was
      greater in men (364 per 100,000) than in women (149 per 100,000). The fatality
      rate for acute stroke in the first month was 38 cases per 100,000 inhabitants.
      Significant risk factors in acute stroke were alcohol abuse, hypertension,
      valvulopathy, earlier episodes of stroke and TIA and emboligenous source of
      cardiac origin.

PMID- 8556595
TI  - [Early reperfusion as a rationale from of therapy in ischemic stroke].
AB  - In the last few years considerable evidence has been seen making it clear that
      although focal neurological deficiency (or ischaemic stroke) develops in parallel
      with intracranial arterial occlusion, the irreversible damage neurons suffer (i e
      necrosis) in many parts of the ischaemic territory is delayed by several hours.
      After an occlusion of the middle cerebral artery, such a lapse is particularly
      evident in the region of the cerebral cortex, an area which could be considered
      as the most peripheral region of the ischaemic territory, also known as
      'penumbra'. This article sets out to review the secondary events in time
      dependent studies which show that many of the consequences of intracranial artery
      occlusion may be totally or partly reversible by reopening the artery 60 minutes
      after. The right middle cerebral artery (MCA) of some two hundred adult Wistar
      rats was blocked up by inserting a nylon monofilament through the outer carotid
      artery. In some of the animals such occlusion was resolved by removing the
      filament minutes or hours later whereas in others light from the MCA remained
      occluded until the end of the experiment seven days later. Many histological and
      histochemical analyses were performed as well as microscopic preparation for each
      subject to obtain information concerning the movement of circulating leucocytes
      and of platelets, the integrity of capillaries as opposed to a circulating
      macromolecule (mw: 43 kd), the development of neuronal necrosis and the
      relationship between neurological deficiency and the level of histological
      damage. Once the MCA was blocked, both neuronal necrosis and leukocyte movement
      followed a somewhat parallel course. A large number of necrotic neurons appeared
      in the next twelve hours, coinciding with the time most intravascular leukocytes
      (neutrophiles) take in making themselves visible around the area affected by the
      blocked artery. In any case, prior to the development of neuronal necrosis and of
      leucotaxis, significant abnormalities appear affecting the perivascular
      astrocytes and capillary endothelial cells. The structural changes in these
      cells, and especially tumefaction, are what cause important abnormalities in
      microvascular integrity appearing several hours before neuronal necrosis. To
      recap: a) despite the fact that leucocyte migration and progressive neuronal
      necrosis follow a parallel course in time, the casual relationship between these
      two physiopathological phenomena is still not firmly established: b) the
      structural changes affecting vascular endothelial cells and astrocytes could
      fulfill a primordial role in possible neuronal necrosis that in the context of an
      experimental infarct is not produced until six hours after arterial blockage; c)
      microvascular deterioration may be reversible by reopening the blockage if this
      is carried out at most 60 minutes afterwards. This point would suggest that
      selective treatment of ischaemic stroke patients using thrombotic agents or
      angioplasty could have beneficial effects.

PMID- 8556597
TI  - [Prevalence of cerebrovascular disease in Spain: a study in a rural area of
      Girona].
AB  - In Spain in recent years two studies have been carried out into the prevalence of
      stroke. In the study made in Girona of the rural population over 64 years of age,
      the prevalence for stroke was 4,012 cases per 100,000 inhabitants. The figure was
      higher for women- 5,072 -than for men 2,675 cases. Transient Ischaemic Attacks
      (TIA) had a prevalence rate of 679 cases per 100,000 population of those aged
      over sixty-nine, being higher for men (1,161 cases) than for women (371 cases).
      The results from Girona differ from the findings in other Spanish regions in that
      the former are lower but at the same time are similar to those obtained in other
      western countries. The greatest risk factors for those over 69 years old were
      arterial hypertension, earlier episodes of TIA, diabetes, auricular fibrillation,
      congestive cardiac insufficiency, chronic bronchitis, myocardial infarction
      peripheral vascular-diseases, arteriosclerosis, heart disease with embolization
      and alcohol abuse.

PMID- 8556598
TI  - [Prognostic factors of supratentorial cerebrovascular accidents].
AB  - Our aim was to delimit prognostic factors in supratentorial stroke based on data
      obtained upon hospitalization. We studied two series of patients, the first being
      150 with brain infarct and the second 135 having intracerebral haemorrhage. We
      analyzed: age, Glasgow and Canadian scales, glucose and urgence haemogram and the
      size of the lesion across its greatest diameter using computerized tomography
      (CT). Follow-up time was until death or one year after the stroke. Those who
      lived longer than one year after were subclassified according to the Rankin scale
      as < 3 and > or = 3. There was a significant difference between those who
      survived for less than one month and those surviving more than one year: their
      age (p < 0.01), average score on the scale (p < 0.001) and size of infarct (p <
      0.05) or haematoma (p < 0.001). The Rankin subgroups < 3 and > or = 3 also
      differed significantly with regard to age. Noteworthy were the unfavourable data:
      Glasgow < 10 points and Canadian < 5 points, in infarcts > 6 cm and haematomas >
      4 cm in diameter. We comment on other evolutionary variables which may influence
      prognostic assessment such as clinical deterioration or CT sensitivity of the
      infarct depending on the carry-out time.

PMID- 8556599
TI  - [Acetyl-salicylic acid and trifusal in the prevention of atherothrombotic
      stroke].

PMID- 8556600
TI  - [A 61-year-old woman with cerebellar syndrome and cortical function
      deterioration].

PMID- 8556601
TI  - [The neurologist profile in Valencian community].
AB  - We carried out a postal opinion poll among members of the Valencian Neurological
      Society with the aim of defining the profile of the Neurologist in our region. We
      received 35 replies (30% answer rate). We can characterize the Neurologist in our
      region as having been an in-house resident doctor (MIR) in 68.6% of cases,
      working in the public health service in 80% of cases and in a hospital also in
      80% of cases. In all cases (100%) general practitioners (GPs) referred patients
      to neurologists as opposed to being referred by other possible routes
      emergencies, other specialties, the patient him or herself-most neurologists
      considering patients should come with adequate clinical history (94.3%), medical
      examination (82.9%) and suspected diagnosis (68.6%). 97.1% expressed the opinion
      that it is the neurologist who must decide the follow-up for neurological
      patients. 85.7% think direct access on the part of the neurologist to Doppler
      techniques is essential and 80% think the same concerning access to
      neuropathological studies, which contrasts with the meager development of these
      techniques in our region. About 70% believe Doppler techniques should be
      performed by the neurologist. 68.6% consider the neurologist should be involved
      in neurology management with decisive powers. 62.9% said subspecialties are
      interesting for research and backup, the most necessary of such subspecialties
      being cerebrovascular pathology, neuromuscular pathology, extrapyramidal
      pathology and epilepsy. Most neurologists were of the opinion that Neurology
      should have nothing to do with Psychiatry or Internal Medicine, although there is
      a need for important relations with Neurophysiology through the setting up of a
      common organization or of functional units. It was generally though the
      neurologist should be involved in teaching at all levels. 77.1% agree with the
      existence of a credit system for continuous assessment in the specialty, most
      (57.1% considering such a scheme should be optional and performed by the regional
      scientific societies (40%).

PMID- 8556602
TI  - [The model of neurological care needs in Valencian community. Commission of the
      analysis of the quality of SVN].
AB  - The model that will based any specialized attention in any healthy area depends
      the necessity of special and primary cares and the criteria of specialized
      practitioners on the type of patients what should be treated. We interview
      following a questionnaire on that question the neurologists of Valencian
      Community in order to know their opinion. The questionnaire includes 47
      neurological topics and we ask the percentage of patients who should be evaluated
      as first visit and as follow-up visits. We used the formula proposed by Kurtzke
      in 1986 in order to calculate the neurological time. The response rate obtained
      was 30%. The whole neurological time was 4,600 hours per 100,000 inhabitants
      yearly, that means 6.9 neurologists-type per 100,000 inhabitants. These data
      suggest that Valencian neurologists agree a model of direct neurological care,
      including diagnosis and follow-up of all neurological topics. These data are
      similar to that obtained in interviews to primary physicians in different healthy
      areas in the Community and confirms the evolution of neurological care to a model
      similar to that in the United States. The topic that require more than 100 hours
      by year are: migraine (1,731) lumbar backache (685), stroke (306), seizures
      (248), Down's syndrome (175.5), alcoholism (150), zoster (122), severe cranial
      trauma (105) and dementia (103).

PMID- 8556604
TI  - [Initial treatment of Parkinson's disease].

PMID- 8556603
TI  - [The neurological care in area hospitals and specialized centers in the Valencian
      community in 1994. Commission of the Analysis of the quality of the SVN].
AB  - The law of Sevicio Valenciano de Salud which aim was to organize a new model of
      healthy care for Valencian Community (CV) coexists with care forms proceeding
      from the past model. This situation provides different matters to valencian
      neurologists. For that reason, the Comision de Analisis de la Calidad de la
      Asistencia Neurologica de la Sociedad Valenciana de Neurologia, wanted to know
      the real situation of neurological care in Healthy Areas of Valencian Community
      and designed a questionnaire which aim was to obtain information on neurological
      care activity and the resources in each Healthy Area. This questionnaire was
      distributed to all neurologists who worked in each Area. The whole neurologists
      number of each Healthy Area. This questionnaire was distributed to all
      neurologists who worked in each Area. The whole neurologist number of Valencian
      Community in 1994 was 64 that means a rate of 1.66 neurologists per 100,000
      inhabitants. Eighteen neuro-psychiatrists persist in 8 Healthy Areas. In the
      areas which included Central Hospitals, the rate was 2.1 Neurologists work in the
      hospitals, in Centros de Especialidades (ambulatory care) or in the two levels
      depending each Healthy Area, and the access of patient to neurological care
      varies taking into account the neurological working place. In the Centros de
      Especialidades, neurologists care a mean of 3,700 visits /year/100,000
      inhabitants nearly and the mean visit time is 15 minutes. Ambulatory clinical
      records are different that records used in hospital but the care is similar.
      Neurologists depend to Medicine Service and realize admittance works in these
      services. The mean hospital neurological admissions are 250/100,000 inhabitants
      yearly and four Country Hospitals have specific beds for neurological patients.
      CT scan is not present in 5 hospitals, Duplex-Doppler in 12, EMG in 9, EEG in 9
      and evoked potentials measurements in 11. Ten hospitals have not clinical
      neurophysiologist, 3 have not rehabilitation team, 7 have not neuropediatrics and
      there are not neurosurgery in any Country Hospital. The conclusions of this work
      includes: A low number of neurologists, the anachronic persistence of neuro
      psychiatric care, the absence of homogeneous care organization and the
      insufficienct of neurological technics in most Healthy Areas in Valencian
      Community.

PMID- 8556605
TI  - [Drug-induced extrapyramidal disorders].
AB  - We analyze 402 drug-adverse events consisting of movement disorders or
      aggravation of parkinsonisms, submitted to Sistema Espanol de Farmacovigilancia
      until 1994. Our aim is to know patient characteristics and the drugs related with
      these submissions. Most of them (64) belong to calcium-entry blocker group (31%)
      and benzamides (27%). Case age intervals more frequent were 11-30 and 60-80 years
      old and the events affect predominantly females. The percentage of serious
      adverse events were near 80%. We think that drug-related parkinsonisms have high
      prevalence rate and that the role of calcium-entry blockers in these events
      should be considered at the moment to prescribe groups.

PMID- 8556606
TI  - [New forms of Parkinsonism in hospice care].
AB  - Parkinson's disease is a well known phenomenon with characteristic evolution and
      clinical picture although having considerable variation in its presenting
      symptoms. From an extra-hospital consulting room we carried out a study of the
      characteristics of the clinical presentation of parkinsonisms in a series of one
      hundred cases so diagnosed from onset. The average age of the patients was around
      66 years with a slight female predominance. Most patients had been referred to us
      by their own GPs. Some 70% of patients came suffering from shaking, 23% for
      slowness or clumsiness and 10% for unsteadiness. 71% of cases had unilateral
      onset and 29% had bilateral onset. Most of the patients we saw arrived at level 2
      on the Hoehn and Yahr scale. The duration of the symptoms was approximately one
      year. In some 27% of cases drug consumption might have brought on parkinsonism.
      Almost two-thirds of these cases brought about by medicaments were being treated
      with cinaricine or flunaricine and nearly one third were undergoing neuroleptic
      treatment. Practically one out of every four cases, and one out of three women,
      could be considered as having iatrogenic parkinsonism. The onset of shaking with
      bilateral affectation is particularly suggestive of drug induced parkinsonism.

PMID- 8556607
TI  - Electro-oculogram in multiple system and late onset cerebellar atrophies.
AB  - The present investigation uses electrooculogram to evaluate multiple system
      atrophy (MSA) and late onset cerebellar atrophies (LOCAs), both idiopathic
      (ILOCA) and late onset autosomal dominant cerebellar ataxia (ADCA). Forty cases
      were clinically examined using scales for cerebellar, pyramidal, parkinsonian,
      mental status and neuroimaging quantitative evaluations. The patients were
      classified into three groups: olivopontocerebellar atrophy (OPCA), striatonigral
      degeneration (SND), Shy-Drager syndrome (SDS), and LOCA. We have used direct
      current electro-oculography in order to establish their validity in making the
      diagnosis. Cerebellar signs were significantly correlated with impaired VOR-fix
      gain and OKN, abnormalities of saccades, and reduced smooth pursuit gain (p <
      0.05). Pons atrophy was significantly correlated with impaired VOR-fix gain (p <
      0.01), abnormalities of saccades (p < 0.01), and reduced smooth pursuit gain (p <
      0.05). Cerebellar hemisphere atrophy was significantly correlated only with
      impaired VOR-fix gain (p < 0.05), and medulla oblongata atrophy only with
      abnormalities of saccades (p < 0.05). Gaze-evoked nystagmus was found in 42.8% of
      patients with OPCA, and only in 14.2% with SND, but was not found in LOCA
      patients (t test, p < 0.05). In patients with OPCA, the combination of gaze
      evoked nystagmus, abnormalities of sinusoidal VOR and reduced OKN gain
      measurements was very frequent, while infrequent in both LOCA (Fisher's exact
      test, p < 0.05) and SND subjects (p < 0.01). SDS also showed abnormalities of the
      oculomotor system.

PMID- 8556608
TI  - [Cerebrovascular accidents in childhood].
AB  - A retrospective study of acute stroke diagnosed in the last ten years (20 cases:
      12 girls and 8 boys) with an incidence rate of 1.26 cases per year per 100,000
      inhabitants under 15 years of age) in our health area. Average age; 7.83 years
      (range: 2 months to 15 years). Confirming diagnosis was performed by computerised
      tomography (CT) scan, magnetic resonance (MR) imaging, echography and/or cerebral
      arteriography. Ten cases of ischaemic stroke and ten of haemorrhagic stroke were
      catalogued. Average follow-up was 5.45 years (range: 9 months to 10.8 years).
      Fibromuscular dysplasia, arthritis and meningitis are predominant in ischaemic
      stroke etiology, there also being one case of Moya-Moya. Haemorrhagic strokes are
      mostly produced by arteriovenous malformation. The predominant presenting form of
      ischaemic stroke was hemiplegia and of haemorrhagic strokes it was intracranial
      hypertension. There were no deaths as a result of ischaemic accidents but three
      in the cerebral haemorrhage group. Treatment was surgical in two cases,
      embolisation in two others and medical support in the remaining sixteen. There
      were no cases of relapse, except in the Moya-Moya case. Clinical position and the
      ability to carry on day to day life were most affected in the cerebral attack
      cases, which would indicate ischaemic stroke recuperation is worse than that for
      haemorrhagic strokes.

PMID- 8556609
TI  - [Hormonal markers of stress in acute cerebrovascular pathology].
AB  - Various studies carried out over the last decade have shown that high glucose
      levels in the blood foster ischaemic brain damage associated with a worse
      evolution of such pathologies. The aim of the study we performed was to try to
      shed some light on whether stress in these patients raised their glucose levels
      adding to a worsening of the patient's clinical picture. We studied 318
      consecutive patients suffering from stroke. We determined fasting glucose levels,
      prolactin and cortisol within the first few hours of hospitalization and
      afterwards at seven to ten days and again at one month after the stroke. Clinical
      severity was evaluated using Toronto and Mathew neurological scales and the
      degree of incapacity was measured using the Barthel functional scale on the three
      aforementioned occasions and Rankin's modified scale six and twelve months after
      the stroke. Clinical severity the first hours after stroke was significantly
      related to glucose levels, such relationship not being observed with prolactin
      and cortisol. Nor did we observe any significant association between glucose and
      these hormones. Likewise the anxiety scale had no relationship with any hormone.
      Studying medium and long term functional incapacity, glucose significantly
      correlated with the Rankin scale although with low dependence, such a
      relationship not being found either with prolactin or cortisol. Our work would
      seem to indicate that blood glucose behaviour is independent of prolactin and
      cortisol levels since we found no such relationship between them.

PMID- 8556610
TI  - [Parkinson disease or drug-induced parkinsonism?].

PMID- 8556611
TI  - [Has it been indicated already to use beta-interferon in patients with multiple
      sclerosis?].

PMID- 8556612
TI  - [Neurological care in Spain].

PMID- 8556613
TI  - [Hematological changes and cerebrovascular disorders].
AB  - Stroke is due to abnormalities in the vascular wall, heart disease or
      hematological abnormalities. This last cause has a low causal rate in stroke but
      despite this its importance is self evident given that there still exists a
      number of stroke patients where etiology cannot be established. An exhaustive
      check was carried out on the different hematological phenomena which may play a
      part in the etiology of ischaemic or hemorrhagic strokes. We analyzed
      abnormalities in the red series, white series and blood cells; coagulapathies;
      discrasias of the plasmic cells and antiphospholipid antibodies. For each of the
      hematological entities, conceptual criteria, their role in brain hemorrhage or
      ischaemia, and therapeutic measures were established.

PMID- 8556614
TI  - [Contribution to studies of seizures in Rett's syndrome. Analysis of critical
      forms of four cases].
AB  - Twenty girls were diagnosed as having Rett's Syndrome (RS) based on criteria
      decided upon in 1988. Fifteen suffered epileptic fits, four of which were
      possible to record by EEG. In this work we report on the clinical EEG semiology
      of these girls. All underwent clinical, biochemical, electroneurophysical,
      neuroimaging and cytogenetic studies. Periodic EEG were carried out while the
      girls were awake and the recorded fits were so obtained. All had night-time EEG.
      Four girls had their first fits between 5 years 4 months and 6 years 5 months
      (average 6 years). The ages at which their attacks were recorded varied from
      seven to eleven years. Two girls presented tonic-axial attacks expressed
      graphically by desynchronisation in the EEG in one case and rhythmically in the
      other, one having had atypical simple absences expressed on EEG as point-wave
      complexes at a rate of two per second, the other presenting two types of attack:
      initially tonic-axial fits expressed as a low amplitude rhythm and a year later
      generalised clonal fits expressed as slow waves with sharp waves in between.
      Outstanding is the fact that despite the diversity of epileptic fits described in
      RS all such attacks recorded were of a generalised type.

PMID- 8556615
TI  - [Adding lamotrigine to the treatment of epilepsy which is difficult to control].
AB  - We studied the effect of adding Lamotrigine to the medication of 36 patients with
      refractory epilepsy (ten with Lennox-Gastaut syndrome and ten with partial
      epilepsy with or without secondary generalization), who were resistant to
      optimized treatment with other drugs and who suffered at least four attacks per
      month. Lamotrigine was administered progressively, the final dose varying between
      25 and 400 mg per day, the average being 192.3 mg. Lamotrigine was suspended in
      four cases (11%) as a result of behavioural abnormalities; three further patients
      showed slight secondary effects; no exanthemata were observed. The average age of
      the 32 patients who continued with treatment was 36.25 years and the average
      duration of epilepsy was 22.41 years. Average follow-up time was 26.9 weeks. In
      the case of two patients (5.55%) the attacks disappeared during follow-up time;
      25 patients (69.4%) experienced at least a 50% objective reduction in the number
      of attacks. In no case was treatment suspended for lack of effect. Two patients
      gave up other drugs and continued monotherapy using Lamotrigine. In nine of the
      ten Lennox-Gastaut syndrome patients the frequency of attacks went down by more
      than 50% and in seven such cases by more than 75%.

PMID- 8556616
TI  - [Single photon emission tomography (SPECT) in severe infantile myoclonic epilepsy
      (EMS)].
AB  - Ten children, three boys and seven girls, with an average age of 7.5 years
      diagnosed as having severe myoclonic epilepsy (SME) underwent single photon
      emission computerised tomography (SPECT) with HMPAO. All had CT, nuclear MR and
      various EEG studies, these findings made at the same time as SPECT. CT and
      nuclear MR produced no relevant data. EEG, although without paroxystic
      abnormalities in two cases, showed generalised discharge in the remaining eight,
      predominantly in the right hemisphere in five. SPECT was normal in two cases (of
      20 and 30 months) and showed areas of hypoperfusion localised in one hemisphere
      in five cases, three in the left and two in the right, and in both hemispheres in
      three cases. Areas of hypoperfusion were located in frontal and/or temporal
      and/or parietal regions. In two cases there was concordance with the prevalence
      of EEG paroxystic activity and in two other cases there was discordance. Our
      findings, with SPECT abnormalities after two years of age, suggest SME could be
      considered as a multifocal epilepsy brought on by secondary structural
      irregularities.

PMID- 8556618
TI  - [Clinical-radiological evaluation of infantile autism and epileptic syndromes
      associated with autism].
AB  - With the aim of ascertaining the existence of medical conditions associated with
      autism, the presence of pre- and perinatal factors, family antecedents as well as
      the prevalence rate of different epileptic syndromes in the juvenile autistic
      population, we carried out a retrospective observational study and looked at the
      medical history of 62 autistic children so diagnosed in the neuropaediatric
      service at Barakaldo Hospital Cruces in the past twenty years. All of them were
      diagnosed by a child neurologist following DSM-III-R criteria, having been by the
      same physician on at least one occasion. From the etiologic point of view, eight
      children (13%) presented specific syndromes, fifteen (23%) presented
      encephalopathies acquired pre-or perinatally, two (3.2%) had brain tumours and
      the remaining thirty-seven (61%) presented critogenetic autism. 47% of autistic
      children were seen to have some kind of epileptic syndrome: six had idiopathic
      epilepsy (juvenile myoclonic epilepsy 1: partial benign epilepsy with Rolandic
      point 2 ; petit mal 1; generalised primary epilepsy grand mal type 1); eleven had
      cryptogenic epilepsy (myoclonic epilepsy 1 ; focal 7; grand mal 1; Lennox 2) and
      secondary epilepsy in eleven other cases (West 4; focal 6; grand mal). In the
      literature an epileptic frequency among autistic subjects is quoted as being
      between 16% and 35% dropping to 6% in slight cryptogenic autistic cases. Our
      frequency rate among autistic children is much higher, reaching 47% of the total
      and affecting 46% of cryptogenic autistic cases. There were no cases of
      polymorphic nursing epilepsy in our series. Idiopathic and cryptogenic epilepsy
      were more frequent in cryptogenic autism.

PMID- 8556617
TI  - [Epilepsy with normal CT: the MR contribution].
AB  - We present a study of 165 patients with fits with normal brain computerized
      tomography (CT) scan or else who showed no evidence as to the etiology of such
      attacks. We analyzed the magnetic resonance (MR) results obtained. In 36.6% of
      cases MR was pathological, the most frequent finding in our series being cerebral
      atrophy (12.8%). We comment on the most important pathology groups, highlighting
      the contribution MR made in our patients.

PMID- 8556619
TI  - [Rett's syndrome].

PMID- 8556620
TI  - [Epilepsy and quality of life].

PMID- 8556621
TI  - [The concept and treatment of drug-resistant intractable epilepsy].
AB  - Epilepsy is considered as being untreatable when attacks present unsatisfactory
      control or else when brought under control only with doses of anti-epileptic
      drugs which produce severe secondary effects. There has to be provable certainty
      that the anti-epileptic drugs were used correctly. Untreatable epilepsy is an
      essential condition for surgical intervention; consequently rigorous therapeutic
      and diagnostic criteria are needed which may also improve control of the attacks.
      About 20% of epilepsies are untreatable. The basic mechanisms of untreatable
      epilepsy are not well known and may be untreatable either from onset or as a
      consequence in the progression of the epileptogenetic process. Various factors
      may be involved in a bad prognosis. Spontaneous improvement is rare from the
      therapeutic point of view and before considering surgery at least two anti
      epileptic drugs should be tried monotherapeutically prior to their use in
      combination. It is well known that bitherapy brings about an important
      improvement in a few cases. Anti-epileptic drugs should be used at their maximum
      tolerable dosage independently of theoretical plasmatic levels.

PMID- 8556622
TI  - [Felbamate: perspectives for new antiepileptic treatment].
AB  - The present work is a review of the new anti-epileptic drug felbamate. Felbamate
      is a dicarbonate with antiepileptic effects in partial attacks and in Lennox
      Gastaut syndrome. This new drug is especially interesting since its
      pharmacological action on test animals would indicate a wider anti-epileptic
      spectrum of activity than most other such drugs. We review the clinical
      pharmacology of felbamate, its development as a new antiepileptic and the new
      clinical control type trials carried out into epilepsy. We also give a summary of
      clinical trial experiments performed using felbamate in the treatment of partial
      refractory attack and of Lennox-Gastaut syndrome. Felbamate has turned out to be
      the first anti-epileptic with specific efficacy in Lennox-Gastaut syndrome.
      Felbamate was approved as an anti-epileptic by the United States Food And Drug
      Administration in July 1993 for clinical use with children suffering from Lennox
      Gastaut syndrome and with adults having partial epileptic attacks. 1994 saw some
      cases of aplastic anaemia and liver failure associated with treatment using
      felbamate which called for a reevaluation of the benefit-risk factors of the
      drug. Its use in the European Union was restricted to Lennox-Gastaut syndrome,
      and rigorous liver function and haematological controls were set up in patients
      so treated. In the United States the FDA also allows treatment using felbamate of
      partial attacks not responding to any type of medicine.

PMID- 8556623
TI  - [Myoclonic encephalopathy induced by diclofenac treatment].
AB  - Some non-steroid anti-inflammatory drugs, and especially diclofenac, may, in some
      susceptible patients bring about the appearance of segmentary myoclonic symptoms,
      which in some cases where there is kidney failure may cause real myoclonic
      encephalopathy. We present the case of a patient admitted into the nephrology
      service suffering from prerenal kidney failure as a result of dehydration. Once
      her kidney problems had been overcome and analytical parameters normalized,
      during treatment with diclofenac for inflammation of the lower left extremity
      arthritic in origin, she showed generalized myoclonic symptoms of action and
      attitude especially in the upper extremities. Neurologic examination showed no
      abnormalities other than certain drowsiness. General analysis and kidney function
      were normal, as was brain CT scan, EEG showed only a general tendency towards
      slowing down. Myoclonic symptoms completely disappeared in the next 24 hours
      after giving diclofenac up, the patient remaining neurologically asymptomatic and
      not showing a similar clinical picture in any subsequent check-up.

PMID- 8556624
TI  - [Intradural extramedullary cavernoma of cauda equina].
AB  - Cavernous angiomas are comparatively rare vascular malformations in the central
      nervous system. Their location at the spinal level is rare, being but 3 to 16% of
      such vascular malformations. Among spinal intradural cavernous malformations most
      are intramedullar, the extramedullar type being less frequent. We have only came
      across five cases in the literature of intradural extramedullar cavernous
      angiomas affecting the cauda equina. We present a new such case with acute onset
      and later chronic evolution affecting the cauda equina through an intradural
      cavernous malformation at the level.

PMID- 8556625
TI  - Spinal cord and bone metastasizing renal tumor of childhood.
AB  - In recent reports on renal tumors of childhood with bone involvement neoplasms
      originally considered to be Wilms tumor have been assigned to new groups. After
      reviewing the literature, we knew that Wilms tumor rarely metastasizes in this
      way. Our case illustrates the unique biological feature of the rare, unfavorable
      histology Wilms tumor variant know as 'clear cell sarcoma of the kidney' (CCSK).
      Metastases to the spinal cord, as observed in our patient are distinctly unusual.
      To our knowledge, only two previous cases have been reported in the world
      literature.

PMID- 8556626
TI  - [Crying epilepsy].
AB  - Crying epilepsy, consisting of the appearance of tears as an epileptic
      phenomenon, is apparently somewhat infrequent. In most cases which it has been
      possible to record, electroencephalography (EEG) indicated a right temporal
      focus. These findings have lent weight to the theory of the existence of
      hemispheric emotion control. We present two cases in which tears were one of the
      clinical signs of epilepsy. In one of the cases EEG showed left temporal focus.

PMID- 8556627
TI  - [Stevens-Johnson syndrome after lamotrigine treatment].
AB  - We report a 18 years old female with Lennox-Gastaut syndrome under treatment with
      sodium valproate, carbamazepine and clonazepam. When seizures increased we
      stopped carbamazepine and introduced lamotrigine slowly. One month later the girl
      developed haemorrhagic erosions in mucoses and limbs with deterioration of her
      general state. Skin biopsy confirmed the diagnosis of erythema multiforme, the
      Stevens-Johnson's form. The immediate withdrawal of lamotrigine and treatment
      with antihystaminics and steroids was followed of a slowly favourable course with
      disappearance of symptomatology one month later. It's another case of Stevens
      Johnson syndrome related to the introduction of lamotrigine in polytherapy.

PMID- 8556628
TI  - [Autistic syndrome associated with refractory temporal epilepsy].
AB  - Autism is a psychopathological disorder of childhood characterized by severe
      lapses in behaviour and cognition and excessive presence of extravagant
      unsuitable behaviour that affects a child's development. It is associated with
      different conditions of the Central Nervous System, especially a high incidence
      of epilepsy. We report a case of autistic syndrome with refractory temporal
      epilepsy, describing its clinical onset, (type of seizures, focal anomalies on
      the EEG, evidence of relation between limbic disfunction and autism.

PMID- 8556629
TI  - [Somatosensory focal seizures as an onset form in adult Moyamoya syndrome].
AB  - Moya-Moya disease is a chronic infrequent vasculopathy. Occasionally such
      abnormalities are found in association with one of many conditions, in these
      cases the angiographic abnormality should be termed Moya-Moya syndrome rather
      than Moya-Moya disease. Although in children the usual manifestations are
      ischemic events and seizures. This clinical presentation is infrequent in adults.
      We present a 42-years-old man with a 1-month history of recurrent right sided
      partial somatosensorial seizures, later he presented a left parietal infarction,
      the angiographic findings were compatible with moyamoya syndrome.

PMID- 8556630
TI  - [A 17-year-old girl with epilepsy, myoclonic jerks and cognitive deterioration].

PMID- 8556631
TI  - [Sleep and deprivation in the epilepsy diagnostic].

PMID- 8556632
TI  - [Activated mechanisms of epilepsy during sleep and wakefulness].

PMID- 8556633
TI  - [Infantile epilepsy and sleep].

PMID- 8556634
TI  - [Interaction of sleep, epilepsy and antiepileptic drugs in an adult].

PMID- 8556635
TI  - [Genetic molecular basis of epilepsy].

PMID- 8556636
TI  - [Characteristics of epilepsy in aged people].

PMID- 8556638
TI  - [Epileptogenesis in the elderly. Part II. Spike-wave confusional states.
      Myoclonic seizure in Alzheimer's disease].

PMID- 8556637
TI  - [Epileptogenesis. Epilepsy and aging].

PMID- 8556639
TI  - [Status epilepticus in the elderly].

PMID- 8556640
TI  - [Clinical aspects of vascular epilepsy in aging].

PMID- 8556641
TI  - [Epilepsy and cerebral aging. Pharmacokinetics of antiepileptic treatment in
      adult age].

PMID- 8556642
TI  - [Spinal cord hemangioblastoma: diagnosis by magnetic resonance imaging].

PMID- 8556643
TI  - [Spinal hematoma due to subarachnoid bleeding].

PMID- 8556644
TI  - [Myoclonic jerks secondary to imipemen].

PMID- 8556645
TI  - [Prevention of neurological disorders of high altitude disease].

PMID- 8556646
TI  - [What should first be considered in the treatment of epileptic patients: control
      of seizures or quality of life?].

PMID- 8556647
TI  - [What should first be considered in the treatment of epileptic patients: control
      of seizures or increase of quality of life?].

PMID- 8556648
TI  - [What should be first considered in the treatment of epileptic patients: control
      of seizures or increase of quality of life?].

PMID- 8556649
TI  - [What should be first considered in the treatment of epileptic patients: control
      of seizures or increase of quality of life?].

PMID- 8556650
TI  - [What should be first considered in the treatment of epileptic patients: control
      of seizures or increase of quality of life?].

PMID- 8556651
TI  - [Treatment of an epileptic patient: a global concept].

PMID- 8556652
TI  - [Historical aspects and synonymy of cluster headache].

PMID- 8556653
TI  - [Cluster headache. Definition and diagnostic criteria].

PMID- 8556654
TI  - [Epidemiological and etiological data on cluster headache].

PMID- 8556655
TI  - [Cluster headache: anatomical and physiopathological basis of pain].

PMID- 8556656
TI  - [Pathogenicity of cluster headache].

PMID- 8556657
TI  - [Clinical features of cluster headache attack].

PMID- 8556658
TI  - [Diagnosis and differential diagnosis].

PMID- 8556659
TI  - [Evolutive forms].

PMID- 8556660
TI  - [Symptomatic treatment of cluster headache].

PMID- 8556661
TI  - [Prophylactic treatment of episodic forms of cluster headache].

PMID- 8556662
TI  - [Prophylactic treatment of chronic cluster headache].

PMID- 8556663
TI  - [Chronic paroxysmal hemicrania].

PMID- 8556664
TI  - [Atypical forms of cluster headache].

PMID- 8556665
TI  - Problem-solving counselling or phone-call support for outpatients with chronic
      illness: effective for whom?
AB  - The purpose of this randomized controlled trial (RCT) was to determine the
      effectiveness of problem-solving counselling or phone-call support provided by
      nurses to outpatients not well adjusted to chronic illness. Subjects (N = 293)
      completed measures at baseline and after the six-month period of intervention for
      psychosocial variables including coping behaviours, purpose in life, and
      psychosocial adjustment to illness. Subjects receiving phone-call support from
      nurses demonstrated less psychological distress. Results also suggest that
      problem-solving counselling improves psychosocial adjustment to chronic illness
      for outpatients who live alone, infrequently use problem-solving coping skills,
      or frequently use avoidance coping methods. As well, outpatients with a low
      purpose in life who show infrequent use of problem-solving coping skills appear
      to benefit most from problem-solving counselling provided by nurses. On the other
      hand, those not well adjusted who frequently use problem-solving coping seem to
      be served more effectively by phone-call support.

PMID- 8556666
TI  - Interconnecting the personal and public: the support networks of public health
      nurse Mona Wilson.
AB  - The life of public health nurse Mona Gordon Wilson reveals the importance of
      women's private lives in explaining their public activities. Although Mona's life
      and personality were also shaped by her gender, class, ethnicity, single status,
      and place in the patriarchal society, this article contends that female
      networking and support groups were essential to her success as a public person.
      Following a brief synopsis of the highlights of Mona's public life, this study
      examines the importance of female networking and support groups in Mona Wilson's
      early years as a nursing student, in her years overseas with the American Red
      Cross, as chief public health nurse on Prince Edward Island, and in retirement
      and old age.

PMID- 8556667
TI  - Visions realized and dreams dashed: Helen Penhale and the first basic integrated
      baccalaureate program in nursing in the west, at the University of Alberta 1952
      1956.
AB  - The first basic degree program in nursing in Canada was established at the
      University of British Columbia in 1919. This program and those that followed
      elsewhere were of the non-integrated form, wherein a diploma program offered by a
      hospital was supplemented by university courses in the arts, humanities, and
      sciences. In 1942 an innovative basic baccalaureate program in nursing was
      established at the University of Toronto; courses in nursing, given by the
      university, were offered in conjunction with university courses in other
      subjects. Only two other attempts were made to set up integrated programs in
      Canada prior to release of the Report of the Royal Commission on Health Services
      of 1964; McMaster University established a program in 1946, and, in an attempt
      that was ultimately unsuccessful, a program was established at the University of
      Alberta in 1952. The purpose of this study was to examine the conditions
      surrounding the initiation and termination of a basic degree program in the 1950s
      at the University of Alberta, in order to understand the key issues in the
      movement to establish basic university degree programs for nurses, and the gender
      discrimination relative to nurses and nursing students that has prevailed in
      health and education. Although the conflict at the University of Alberta was a
      very difficult one for the nurses involved, and although the Director who had the
      temerity to establish the program relinquished her position when the program was
      summarily terminated, this episode in Canadian nursing history provides insight
      into the climate in which baccalaureate nursing education existed and into some
      of the issues relative to its development.

PMID- 8556668
TI  - A blueprint for the development of the profession of nursing: the legacy of F.
      Moyra Allen and Joan Gilchrist.

PMID- 8556669
TI  - Early tuberculosis nursing in British Columbia.
AB  - Tuberculosis was Canada's leading cause of death at the turn of the century, with
      a mortality rate in 1900 of about 200 per 100,000 population. By 1944 mortality
      was reduced to about 20 per 100,000. It is postulated that between 1895 and 1945
      nurses filled a new, unique, and essential role in bringing the disease under
      control. This article reports on the first phase of a study to examine the role
      of nurses in controlling TB in British Columbia between 1895 and 1945. This
      preliminary study covers the period 1895 to 1920, when B.C.'s first university
      courses for public health nurses had not yet been established but during which
      nurses began to play a significant public health role by nursing TB patients.
      Drawing on primary and secondary sources, the authors establish baseline data,
      examine early TB nursing care in B.C., identify critical events, and determine
      whether the research should proceed.

PMID- 8556670
TI  - Sources in nursing historical research: a thorny methodological problem.

PMID- 8556671
TI  - [A comparative study on the self-care needs as perceived by women treated for
      depression].
AB  - Nurses' knowledge of the help they can offer women being treated for depression
      are primarily based on models borrowed from other disciplines rather than on
      those from nursing itself. Using Orem's nursing model (1991), this comparative,
      descriptive study (a) described the requisites for self-care, according the value
      ascribed to them by women being treated for depression; (b) compared these to
      those of women not being treated for an emotional problem; and (c) identified the
      types of assistance that would fulfil the self-care requisites perceived by women
      being treated for depression. The results indicated that, compared to women not
      being treated (n = 30), those being treated (n = 30) ascribed significantly
      higher values to self-help requisites related to assertiveness, mood, and self
      esteem. In contrast, women in the comparison group attributed more importance to
      various means of improving their interpersonal relations. Women being treated for
      a depressive episode felt they needed assistance in areas mainly related to self
      esteem, mood, and knowledge of depression to fulfil their self-care requisites.
      Only rarely did they consider the nurse or social network to be valuable sources
      of help. The implications of these results for nursing interventions is
      discussed. Recommendations are made on directions for further research.

PMID- 8556672
TI  - Assessment of adherence to dietary recommendations.

PMID- 8556673
TI  - Infant feeding practices in Newfoundland and Labrador.

PMID- 8556674
TI  - Infant feeding practices: are CPS guidelines followed?

PMID- 8556675
TI  - A survey of breakfast-eating among young schoolchildren in northeastern Ontario.

PMID- 8556676
TI  - Sociodemographic factors related to breastfeeding in Ontario: results from the
      Ontario Health Survey.

PMID- 8556677
TI  - Illnesses of one-year-old children: a health diary study.

PMID- 8556678
TI  - Health policy planning: a look at consumer involvement in Nova Scotia.

PMID- 8556679
TI  - School contact tracing for tuberculosis using two-step Mantoux testing.

PMID- 8556680
TI  - Predictors of caregivers' dissatisfaction with community long-term care services
      for seniors: results from the Canadian Study of Health and Aging.

PMID- 8556681
TI  - [Automobile driving with alcohol impaired abilities in young people from rural
      areas in Quebec: a comparison of the years 1983 and 1992].

PMID- 8556682
TI  - The prevalence of HIV-1 infection among inmates in Ontario, Canada.

PMID- 8556683
TI  - Health professionals' perceptions of partnership with self-help groups.

PMID- 8556684
TI  - A controlled trial of the effect of HEPA vacuuming on childhood lead exposure.

PMID- 8556685
TI  - Urban air quality and human health: a Toronto perspective.

PMID- 8556686
TI  - Role of caloric restriction in the prolongation of life.
AB  - Restriction of caloric intake increases longevity, slows the rate of functional
      decline, and reduces incidence of age-related disease in a variety of species.
      Most laboratory rodent studies have initiated restriction before puberty, whereas
      ongoing studies in nonhuman primates utilize restriction in adulthood. The
      mechanism of action of caloric restriction remains unknown; however, data suggest
      that cellular functions are altered in such a way that destructive by-products of
      metabolism are reduced, and defense or repair systems are enhanced by this
      nutritional manipulation.

PMID- 8556687
TI  - Vitamin E and aging immune response.
AB  - Aging is associated with decline in immune response, which contributes to
      increased incidence of infectious and neoplastic diseases. This article
      summarizes animal and human studies demonstrating the immuno-stimulatory effects
      of vitamin E for the immune response in aging. The mechanisms of the effect of
      vitamin E are discussed.

PMID- 8556688
TI  - Diet, aging, and cancer.
AB  - As we consider the epidemiologic evidence on diet-cancer associations, we should
      keep in mind the geographical differences in cancer incidence that stimulated us
      to look for a diet-cancer link in the first place. For many cancers, the
      variation in geographic incidence is in the range of an order of magnitude (see
      Table 2). Thus, if variation in dietary components are primarily responsible for
      these huge geographic variations in cancer incidence, then the effect of dietary
      components will not be subtle. Based on the magnitude of geographic variation,
      one might be primed to look for large differences in cancer incidence associated
      with different dietary intakes--relative risks of two or greater. This is not to
      say that a true relative risk of 1.2 or 0.8 for cancer associated with some
      dietary habit is not potentially important, but it will not get us very far along
      the way of explaining the geographic variation. The recommendation of the
      National Research Council is the consumption of five servings of fruit and
      vegetables daily. This level of consumption would place one in the "high
      consumption" group in most of the epidemiological studies showing a strong
      association between fruit and vegetable intake and cancer. Unfortunately, only
      10% of the U.S. population actually consumes the recommended amount. Conversely,
      20% to 35% of the U.S. population consume levels of fruits and vegetables that
      put them in the "low consumption" groups. Although causality cannot be
      established, the evidence is overwhelming that some constituent(s) of fruits and
      vegetables is (are) protective; low intake carries a greater than two-fold risk
      of cancer. The risk of cancer associated with low fruit or vegetable consumption
      may only be exceeded by that of smoking. In the typical diet in the United
      States, the main source of antioxidant nutrients vitamin C, carotenoids, and
      vitamin E comes from fruit and vegetable consumption. Without a complete
      understanding of the mechanism for the effect of fruits and vegetables or
      antioxidants, the epidemiologic evidence strongly supports the clinical benefits
      that can be achieved by promotion of consumption (Table 5).

PMID- 8556689
TI  - Diet in the prevention and treatment of atherosclerosis. A perspective for the
      elderly.
AB  - Atherosclerosis is the leading cause of coronary heart disease among older
      persons. With an increasing elderly population, cardiovascular disease has become
      an urgent public health concern. Diet plays an important role in atherogenesis
      with known beneficial effects on major risk factors among the younger population-
      cholesterol, hypertension, and diabetes. Intervention studies are needed to
      establish the benefits of diet therapy in the elderly segment of the population.
      Efforts are also needed to educate the elderly and health professionals about the
      benefits of a healthy Step I diet.

PMID- 8556690
TI  - Diet and diabetes in the elderly.
AB  - This article draws attention to some of the unique aspects of diabetes mellitus
      in the elderly and outlines the principles of management of diabetes in this age
      group with emphasis on diet therapy. The implications of the Diabetes Control and
      Complications Trial for the elderly person with diabetes is also briefly
      discussed. The new nutrition recommendations of the American Diabetes Association
      are summarized, and the evolving enhanced role of the dietitian in the management
      of diabetes is highlighted.

PMID- 8556691
TI  - Patient care of osteoporosis.
AB  - Osteoporosis is a condition of excessive skeletal fragility that afflicts more
      than 25 million Americans and results in over one half million fractures per year
      in the United States. Evaluation of patients presenting with symptoms of
      osteoporosis includes measurement of serum 25 hydroxy, vitamin D, thyroxine,
      thyroid-stimulating hormone, serum protein electrophoresis, in addition to blood
      count, urinalysis, and multichannel screen. Spine and other films are indicated
      as necessary, and although bone density measurements are useful, they are
      somewhat restricted in availability. There are lifestyle measures that influence
      the cause as well as the treatment of osteoporosis. Symptomatic patients benefit
      most by interventions that include nutrition, physical fitness, calcium, and
      vitamin D.

PMID- 8556692
TI  - Effects of age on nutrient requirements.
AB  - The effects of age on nutrient requirements are difficult to quantify for older
      adults because there is great variability in aging. There are trends in changes
      that have been identified through longitudinal studies that indicate that,
      although there is a decrease in energy requirement with advancing age, there is
      not a parallel decrease in the need for most other nutrients. In fact, protein
      requirements per kilogram of body weight may increase; increases for certain
      vitamins may be due to their unique absorptive and metabolic processes that may
      be affected by chronic conditions. There is little evidence to support changes in
      mineral needs unless there is an association with the management of a chronic
      condition. Fluid requirements to prevent dehydration must be addressed in elderly
      people.

PMID- 8556693
TI  - Failure to thrive in the elderly.
AB  - Failure to thrive in the elderly is a syndrome and not a diagnosis. It
      encompasses a number of conditions characterized by progressive weight loss and
      decrease in function. For purposes of diagnosis and treatment, failure to thrive
      can be divided into nonorganic and organic causes. Nonorganic causes include
      psychosocial problems and difficulties with physical function. Organic causes
      include known diseases and, possibly, unknown age-associated changes in
      nutrition, regulation of inflammation, and anabolic and catabolic hormones.

PMID- 8556694
TI  - The role of nutrition in increased morbidity and mortality.
AB  - Up to 65% of the hospitalized elderly are protein-energy undernourished at
      admission or develop serious nutritional deficits while hospitalized. These
      undernourished patients are at an increased risk of developing serious in
      hospital complications, the likelihood of developing a complication increasing in
      relation to the severity of the nutritional deficits. Several studies suggest
      that aggressive nutritional support targeted to these undernourished patients may
      be beneficial both in terms of rectifying their nutritional deficits and
      improving their clinical outcomes; however, these findings have not been
      confirmed. There must be a greater understanding of the nutritional needs in the
      hospitalized elderly to guarantee optimal care.

PMID- 8556695
TI  - Nutrition assessment practical approaches.
AB  - Because of the insidious nature of malnutrition in the elderly and its mimicking
      the usual aging process, it is important to recognize early warning signs of
      risks for malnutrition. Because the majority of individuals are encountered at
      times of a specific event (i.e., illness, injury, surgery, or annual examination)
      the physician needs to be cognizant of the triggers or alerts of poor nutritional
      health during history/physical and laboratory examinations for the particular
      event. Only then will early detection and applicable interventions provide a
      salutary paradigm shift towards prevention, whether primary, secondary, or
      tertiary. A high degree of suspicion, a thorough history, and physical
      examination coupled with pertinent laboratory data can identify the elderly at
      risk. Those in need of more comprehensive nutrition screen and assessment are
      examined with the tools developed by the NSI, which encompass not only the
      routine medical and dietary history and physical exam but also an expansive look
      at the older individual's psychosocial, functional, socioeconomic, and drug use
      aspects that are more indirect and significant determinants of risk. Based on
      parameters from a Level II Screen, measurable indicators are available that
      provide the nutrition assessment necessary for an overall healthcare plan of
      selected interventions. Future research should provide more practical, age, sex,
      and culturally specific nutrition parameters. The main factor in the
      implementation of a practical, comprehensive geriatric nutrition screening and
      assessment program is the clinician's imagination and motivation.

PMID- 8556696
TI  - Approaches to the nutritional support of the older patient.
AB  - Malnutrition is a common problem in older persons, and in the presence of
      disease, is accompanied by increased morbidity and mortality. This article
      provides a rational approach to the nutritional care of the common nutritional
      problems that occur in the elderly. These problems include obesity, a condition
      that occurs with some prevalence in older persons, weight loss and being
      significantly underweight, and hypoalbuminemic malnutrition. An approach to the
      nutritional management of patients with pressure ulcers is also discussed.

PMID- 8556697
TI  - Exercise, nutrition, and aging.
AB  - Advancing adult age is associated with profound changes in body composition. Age
      related loss in skeletal muscle has been referred to as sarcopenia and is a
      direct cause of the age-related decreased in muscle strength. Resistance training
      is an effective means of preserving or increasing skeletal muscle mass and
      functional status in the elderly. In addition, resistance training has been
      demonstrated to increase energy requirements, protein retention, bone mass, and
      levels of physical activity in healthy elders as well as the very old and frail.

PMID- 8556698
TI  - Effect of anabolic hormones and insulin-like growth factor-I on muscle mass and
      strength in elderly persons.
AB  - The secretion of growth hormone and testosterone declines with age. Because these
      hormones have prominent anabolic effects on skeletal muscle, part of the age
      related decrease in muscle mass and strength have been attributed to declining
      levels of these hormones; however, growth hormone replacement in healthy elderly
      people has produced side effects but no functional benefit. In contrast, short
      term growth hormone and insulin-like growth factor 1 treatment have reduced
      protein loss and improved function during acute catabolic states. Although
      testosterone replacement has increased lean body mass and improved the sense of
      well being, functional benefit has not been clearly demonstrated, and the risks
      of long-term replacement have not been defined.

PMID- 8556699
TI  - Modulation of carcinogen-induced DNA damage and repair enzyme activity by dietary
      riboflavin.
AB  - Formation of single strand breaks in nuclear DNA induced by hepatocarcinogens
      aflatoxin B1 and N-nitrosodimethylamine was observed to be more pronounced in
      rats maintained on a riboflavin-deficient diet compared to that on a normal diet.
      This increased damage was reversed on riboflavin supplementation. The induction
      of repair enzymes poly(ADP-ribose) polymerase, DNA polymerase beta and DNA ligase
      was significantly higher in riboflavin-deficient rats following DNA damage caused
      by the administration of carcinogens. Riboflavin supplementation brought down the
      induction to the levels found in rats maintained on normal diet. Since damage to
      DNA and its altered repair may relate to carcinogenesis, modulation of these
      parameters by riboflavin suggests a potential chemopreventive role of this
      vitamin.

PMID- 8556700
TI  - Lipids status in human breast cyst fluids.
AB  - Benign mammary gross cystic disease is the most common breast lesion; women with
      apocrine changes of epithelium lining the cysts are at higher risk for developing
      breast cancer than the normal population. Total cholesterol, high- and low
      density lipoproteins fractions, triglycerides and phospholipids, lipase activity
      and total lipid concentrations were measured in cyst fluids and sera from 89
      women affected by gross cystic breast disease. Total cholesterol and high-density
      lipoprotein content were significantly (P < 0.001) greater in pooled cyst fluids
      than normal sera. Moreover, data analyses show a significant increase in the mean
      values of total lipids and lipase activity in metabolically active apocrine
      cysts, when compared to the flattened cysts (P < 0.001). The lipids feature of
      apocrine cysts could represent an altered expression of biosynthetic activity of
      the surrounding apocrine cell surface glycolipid and steroidogenic metabolism and
      may provide further knowledge about the functional stage changes of gross breast
      cysts.

PMID- 8556701
TI  - Immunohistochemical demonstration of 3,2'-dimethyl-4-aminobiphenyl DNA adduct
      formation in various organs of Syrian golden hamsters.
AB  - 3,2'-Dimethyl-4-aminobiphenyl (DMAB), known to be a wide-spectrum genotoxic
      carcinogen in rats, is also tumorigenic to hamster organs such as the
      forestomach, small and large intestines, gallbladder and urinary bladder. Using a
      specific antibody against DMAB-DNA adducts, adduct formation in various organs of
      Syrian golden hamsters after single s.c., i.g. or i.p. injections of DMAB was
      immunohistochemically examined in relation to its carcinogenic specificity. The
      nuclei of basal cells of forestomach, epithelia of small intestine, large
      intestine, gallbladder and urinary bladder of hamsters were stained to various
      degrees. However, no differences in the formation of DMAB-DNA adducts were
      observed between these and non-target organs regarding carcinogenicity. The
      staining intensity after i.g. or i.p. injections was slightly stronger than after
      s.c. injection. In line with previous findings for rats, the present results
      indicate that adduct formation is necessary but not itself sufficient for tumor
      induction in the Syrian golden hamster.

PMID- 8556702
TI  - Prognostic value of immunohistochemically detected HER-2/neu oncoprotein in
      endometrial cancer.
AB  - HER-2/neu (c-erbB-2) oncoprotein is a transmembrane glycoprotein and may function
      as a growth factor receptor being involved in the regulation of cell growth and
      cell transformation. We performed an analysis of 100 patients with endometrial
      cancer stage FIGO I to IV using an immunoperoxidase technique on formalin-fixed,
      paraffin-embedded tissue samples in order to determine HER-2/neu oncoprotein
      expression. HER-2/neu oncoprotein was expressed in the tumors of 21 patients
      (21%). Clinical stage, histologic stage, histologic grade and death of invasion
      did not correlate with HER-2/neu oncoprotein expression. We found HER-2/neu
      oncoprotein in all clinical stages and therefore it does not seem to be a late
      event in the natural history of endometrial cancer. HER-2/neu oncoprotein
      expression was associated with poor overall survival (log-rank P-value 0.04).

PMID- 8556703
TI  - Immunological localisation of melanocortin 1 receptor on the cell surface of
      WM266-4 human melanoma cells.
AB  - The localisation of melanocortin 1 receptor (MC1R) in WM266-4 human melanoma
      cells was investigated by applying an antipeptide antiserum specific for the
      cloned human MC1R (MSH receptor). In enzyme-linked immunosorbent assay (ELISA),
      the immunoreactivity was detected in the membrane fraction of WM266-4 cells. The
      ELISA reactivity could be inhibited by an antiserum pre-absorbed with its
      specific synthetic peptide. In immunocytochemistry, the specific immunoreactivity
      was demonstrated on the surface of the cells by using either biotin-avidin
      immunoalkaline phosphatase- or TRITC-staining method. These results indicate that
      the MC1R is prominently present on the plasma membrane of WM266-4 human melanoma
      cells.

PMID- 8556704
TI  - Effects of novel 3,4-bisphenylhex(3)enes on cell proliferation in malignant and
      normal cells.
AB  - The growth-inhibitory effect of several newly synthesized alkyl derivatives of
      3,4-bisphenylhex(3)ene was studied in four tumor cell lines and three healthy
      primary cell systems. A marked inhibition of cell proliferation was noted in the
      neoplastic cells but not in the primary systems. No effect on the cytoplasmic or
      mitotic microtubule system but an increase in the gross level of 5-methylcytosine
      in nuclear DNA was observed. It is speculated that the selective growth
      inhibition of tumor cells is due to DNA-hypermethylation.

PMID- 8556705
TI  - Photothermal effects on murine mammary tumors using indocyanine green and an 808
      nm diode laser: an in vivo efficacy study.
AB  - Murine mammary tumors were treated using indocyanine green and an 808 nm diode
      laser, and the in vivo chromophore-enhanced photothermal effects on the tumor
      burden and on tumor rat survival were investigated. The power of the laser was
      selected in the range of 5-10 W, and irradiation duration 3-5 min. One percent
      aqueous indocyanine green solution in a volume of 100-200 microliters was
      administered in situ, either acutely or 24 h prior to the treatment. The
      photothermal interaction was apparent under all our treatment conditions with a
      well-defined spatial containment in this study and the tumor growth was slowed
      after treatment. The post-treatment observation showed tumor recurrence and
      metastasis; no long-term survival was achieved with the single application of
      laser in conjunction with indocyanine green. Our results pose a question on the
      efficacy of the photothermal interaction even though tumor cell destruction can
      be achieved in a large and controlled scale. However, this highly selective
      photothermal impact on the tumor tissue did suggest that this method be applied
      repeatedly to be more effective and be used as the precursor of other modalities,
      such as chemotherapy, radiation therapy, immunotherapy, and surgery.

PMID- 8556706
TI  - Ha-ras oncogene expression abrogates a pH dependent endonuclease activity of
      apoptosis in normal rat kidney cells.
AB  - To investigate the role of oncogene expression in the resistance to tumor
      necrosis factor-alpha (TNF), we transfected the mutated T24-Ha-ras oncogene into
      the murine kidney cell line NRK and an alternative murine cell line C127 cells.
      The resulting transfectants, NRK-Ha and HC127, were assayed for TNF mediated
      cytotoxicity. Cellular cytotoxicity of 45% over 48 h occurred with the NRK cells.
      However, ras transfectant NRK-Ha cells demonstrated 0% cytotoxicity over the same
      period. Both C127 cells and the ras transfectant HC127 demonstrated 40% and 25%
      cytotoxicity, respectively, over 48 h when incubated with TNF. Furthermore, DNA
      isolated from NRK, C127, HC127, but not NRK-Ha cells revealed the presence of DNA
      fragmentation 'ladders' indicative of successful apoptosis when the cells were
      incubated with TNF. To determine the possible mechanism in which the ras oncogene
      may have protected the NRK-Ha cells from TNF mediated cytotoxicity and apoptosis,
      total nuclear endonucleases from the NRK cells and the ras transfectant NRK-Ha
      cells were isolated. We determined that the endonuclease activity in the NRK and
      the ras transfectant NRK-Ha cells was a pH dependent endonuclease. Significant
      degradation of the target DNA was observed only in pH 4-6 buffers containing the
      endonuclease. Furthermore, preliminary intracellular pH analysis suggested that
      while the NRK cells have an intracellular pH of 6.0, the ras transfectant NRK-Ha
      cells have an intracellular pH of 7.2 and may have abrogated its pH dependent
      endonuclease. Both the C127 cells and the ras transfectant HC127 cells did not
      express a pH dependent endonuclease but rather a Ca2+/Mg2+ dependent
      endonuclease. Furthermore, preliminary intracellular pH analysis suggested that
      both the C127 and HC127 cells have the same intracellular pH. Our results
      indicate that in normal rat kidney cells, ras oncogene transfection may cause a
      disruption in the endonuclease activation involved in apoptosis.

PMID- 8556707
TI  - p53 functional loss in a colon cancer cell line with two missense mutations
      (218leu and 248trp) on separate alleles.
AB  - We have sequenced p53 in three colon cancer cell lines capable of autonomous
      proliferation. SNU-C1 and SNU-C4 cells, whose autonomous growth is dependent upon
      autocrine stimulation of epidermal growth factor receptor (EGFR), had wildtype
      p53 sequence of exons 4-9. In contrast, an EGFR ligand-independent cell line, SNU
      C5, had heterozygous missense mutations affecting codons 218 (valine to leucine)
      and 248 (arginine to tryptophan) of p53. Bacterial cloning of p53 from SNU-C5
      cells showed that the 248trp and 218leu mutants were both expressed and on
      separate alleles. 248trp is a common 'hot spot' mutant of p53 with variable
      dominant negative activity depending on the celullar context. Valine 218, in
      contrast, is rarely affected by mutation in cancers and is located in a region of
      the hydrophobic core domain away from 'hot spot' DNA contact sights. However,
      valine 218 is completely conserved across species, prompting us to investigate
      the function of 218leu in SNU-C5 cells. SNU-C5 cells exhibited complete loss of
      normal p53 function as evidenced by over-expression of p53 protein and by failure
      to show induction of p53, waf-1, mdm-2 or G1/S arrest in response to the DNA
      damaging agent, bleomycin. In a yeast p53 functional assay (FASAY), 50% of the
      clones were unable to transactivate a p53-specific promoter required for yeast
      colony expansion at 25, 30 or 37 degrees C. Sequencing of the p53 insert from
      several randomly selected wild-type and mutant yeast clones revealed that 218leu
      bearing clones retained their ability to transactivate the p53-specific promoter.
      As expected, the 248trp-bearing clones lost this function. These data indicate
      that although 218leu retains normal transactivation activity on a p53 promoter in
      yeast at physiological temperatures, it is not capable of normal p53 function in
      the presence of a 248trp allele in SNU-C5 cells. It remains unclear whether the
      strong dominant negative activity of 248trp in SNU-C5 cells is related to the
      cellular context or to an unresolved abnormality of 218leu function.

PMID- 8556708
TI  - Expression of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible cytochrome P4501A1 in
      human splenic lymphocyte cultures.
AB  - The induction of cytochrome P4501A1 (P4501A1) and P4501A1-specific 7
      ethoxyresorufin O-deethylase (EROD) activity by 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) was investigated in human splenic lymphocytes cultures. EROD
      activity was induced by TCDD in mitogen (phytohemagglutinin and pokeweed mitogen)
      stimulated blast cells but not in the resting cells. TCDD markedly induced EROD
      activity in a dose- and time-dependent manner. The expression of P4501A1 mRNA was
      increased by TCDD in mitogen-stimulated cells as detected by Northern blot
      analysis. These findings support the conclusion that TCDD induced the expression
      of P4501A1 gene, resulting in increased EROD activity in mitogen-stimulated human
      splenic lymphocytes cultures.

PMID- 8556709
TI  - Effect of the activated Raf protein kinase on the human multidrug resistance 1
      (MDR1) gene promoter.
AB  - Revealing the regulatory mechanism of the multidrug resistance 1 (MDR1) gene is
      important to gain understanding of MDR in tumor cells. Using MDR1 deletion
      constructs and the 22W mutant of c-Raf in which the NH2-terminal half has been
      deleted, we examined the effect of the activated Raf on human MDR1 promoter
      activity in transient expression assay and stable transfectants of GHE-L cells. A
      DNA sequence exhibiting strong activation of MDR1 promoter by 22W was located
      between -197 and -136 containing the upstream heat shock element (HSE) motifs
      without other regulatory elements, whereas the MDR1 deletion construct containing
      downstream HSE motif showed a relatively weaker activation by 22W. We observed
      that the activated Raf significantly potentiated the induction of MDRCAT activity
      in GHE-L cells by sodium arsenite or heat shock, which stimulates heat shock
      factor (HSF) binding to HSE. In addition, protein kinase A inhibitor (H-87)
      blocked the activation of the MDR1 promoter by 22W in GHE-L cells in a dose
      dependent manner. From these results, we propose the possibility that Raf- and
      protein kinase A-dependent pathways control the transcription of MDR1 gene via a
      mechanism involving the modulation of HSF activity.

PMID- 8556710
TI  - Vitamin E blocks the cytotoxic effect of gamma-linolenic acid when administered
      as late as the time of onset of cell death--insight into the mechanism of fatty
      acid induced cytotoxicity.
AB  - Certain polyunsaturated fatty acids can selectively kill tumor cell lines while
      causing little to no harm to normal cell lines. However, the mechanism of this
      cytotoxicity is only partially understood. Antioxidants such as vitamin E have
      been shown to be capable of completely blocking the cytotoxic response when
      administered concomitantly with the fatty acid. We report here that when vitamin
      E was added as late as 6 days following fatty acid treatment, at a time point
      when the process of cell death was well underway, any further development of cell
      death was blocked. This implies that the mechanism of fatty acid induced
      cytotoxicity does not involve a gradual compromising of the cell over the 5-7 day
      time course of cell death. Instead, the event triggering cell death is an
      oxidative phenomenon occurring over a short time span of minutes or hours, not
      days, and is completely blocked by vitamin E.

PMID- 8556711
TI  - Genomic methylation patterns of the Dunning R-3327 prostate adenocarcinoma
      system.
AB  - Genomic methylation patterns of Dunning R-3327 cell lines anaplastic tumor-1 (AT
      1), anaplastic tumor-3 (AT-3), metastasis-lymph and lung (Mat-LyLu) and
      metastasis-lung (Mat-Lu), and Mat-LyLu cells treated with difluoromethylornithine
      (DFMO), and retinoic acid (RA) have been analyzed. Each cell line was digested
      with HpaII and MspI restriction endonuclease enzymes to characterize methylation
      patterns, at the interior cytosine of the sequence CmCGG. Identical molecular
      weight banding patterns were found for both HpaII and MspI digests in normal
      dorsal prostate (NDP) used as a control. Both the treated and non-treated Dunning
      R-3327 cells digested with HpaII and MspI, displayed similar banding profiles
      from those seen in NDP solid tissues, indicative of a progressive loss of
      methylation at CCGG sites.

PMID- 8556712
TI  - Increased oxidative DNA damage in livers of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      treated intact but not ovariectomized rats.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a more potent hepatocarcinogen in
      female than in male or ovariectomized rats. A possible mechanism for this
      increased sensitivity is through enhanced metabolic activation of estrogens by
      TCDD-induced enzymes leading to oxidative damage in the cell. As a marker for
      oxidative DNA damage, 8-oxo-deoxyguanosine (8-oxo-dG) was quantitated in livers
      of intact and ovariectomized Sprague-Dawley rats chronically treated with TCDD
      (125 ng/kg per day) with and without diethylnitrosamine as initiator. Elevated
      levels of 8-oxo-dG were detected in a significantly greater number of the intact
      compared to ovariectomized TCDD-treated rats. Expression of CYP1B1 mRNA, a newly
      identified cytochrome P450 with proposed estrogen hydroxylase activity, was
      highly induced by TCDD. The results are consistent with the hypothesis that
      increased metabolism of endogenous estrogens to catechols by TCDD-induced enzymes
      may lead to increased oxidative DNA damage and hence contribute to TCDD-mediated
      hepatocarcinogenicity in female rats.

PMID- 8556713
TI  - Arsenite, but not cadmium, induces ornithine decarboxylase and heme oxygenase
      activity in rat liver: relevance to arsenic carcinogenesis.
AB  - Sodium arsenite and cadmium chloride, were administered orally to adult female
      rats at 21 and 4 h prior to sacrifice. Liver, lung, skin and urinary bladder were
      the tissues studied. DNA damage, cytochrome P450, glutathione content (GSH),
      ornithine decarboxylase (ODC), serum alanine aminotransferase and heme oxygenase
      activity were measured. Sodium arsenite increased rat hepatic ODC activity at 1.6
      and 24.6 mg/kg and hepatic heme oxygenase activity at 8.2 and 24.6 mg/kg, but did
      not cause any DNA damage. Cadmium chloride did not affect any of the six
      parameters tested. These findings suggest that sodium arsenite may be a promoter
      rather than an initiator of carcinogenesis.

PMID- 8556714
TI  - Tumor necrosis factor alpha and lymphotoxin stimulate human myeloblastic leukemia
      cell (ML-1) invasion through a reconstituted basement membrane (Matrigel) with
      concomitant induction of 92 kDa gelatinase secretion.
AB  - We have examined the effects of tumor necrosis factor alpha (TNF) and lymphotoxin
      (LT) on gelatinase (72 kDa and 92 kDa) and tissue inhibitor of metalloprotease 1
      (TIMP1) secretion by human myeloblastic leukemia cells (ML-1) in vitro. TNF (0.1
      30 ng/ml) significantly stimulated 92 kDa gelatinase secretion in a dose
      dependent manner, but did not significantly stimulate 72 kDa gelatinase
      secretion. LT also significantly stimulated 92 kDa gelatinase secretion, but the
      stimulation was less effective compared to TNF. TNF, but not LT, concentrations
      at 30 ng/ml slightly stimulated TIMP1 secretion. Because 92 kDa gelatinase is
      thought to play a pivotal role in tumor invasion, we examined the effect of TNF
      or LT on ML-1 cell invasion through a reconstituted basement membrane (Matrigel).
      Exposure of ML-1 cells to TNF (3, 10, and 30 ng/ml) or LT (3, 10, and 30 ng/ml)
      stimulated ML-1 cell invasion through Matrigel in a dose-dependent manner in
      vitro. The data suggest that TNF- and LT-stimulated 92 kDa gelatinase secretion
      could play an important role in TNF- or LT-stimulated ML-1 cell invasion.

PMID- 8556715
TI  - Ability of okadaic acid and other protein phosphatase inhibitors to mimic the
      stimulatory effects of 12-O-tetradecanoylphorbol-13-acetate on hydroperoxide
      production in mouse epidermis in vivo.
AB  - The non-12-O-tetadecanoylphorbol-13-acetate (TPA)-type tumor promoters, okadaic
      acid (OA) and calyculin-A (CAL-A), which neither interact with the phorbol ester
      receptor nor directly activate protein kinase C, mimic the stimulatory effects of
      and thapsigargin on hydroperoxide (HPx) production in mouse epidermis in vivo.
      The time course and dose dependency for the stimulation of HPx production by O
      and TPA are similar. HPx production is maximally stimulated 16 h after two
      applications of 2 nmol of OA at a 48-h interval. However CAL-A is a stimulator of
      HPx production about 4 times more potent than OA or TPA. Combinations of TPA and
      OA or CAL-A have subadditive effects on HPx production. The discrepancies between
      the abilities of various serine/threonine protein phosphatase (PP) inhibitors to
      stimulate HPx production suggest that PP inhibition alone is not sufficient for
      this response. Cycloheximide, Ca2+ antagonists, oxypurinol, diphenyliodonium,
      nordihydroguaiaretic acid, bromophenacyl bromide, antiinflammatory agents, and
      antihistamines block or decrease OA-stimulated HPx production. Although most of
      these inhibitors may have more than one action, their effects suggest that
      protein synthesis, Ca2+, xanthine oxidase and NADPH oxidase activities, the
      lipoxygenase pathway of arachidonic acid metabolism, and vascular permeability
      may be involved in the inflammatory and HPx responses that occur after tumor
      promoter treatment. The increased HPx-producing activity of the epidermis,
      therefore, may be a common event resulting from the inflammatory and tumor
      promoting actions of diverse TPA- and non-TPA-type agents.

PMID- 8556716
TI  - Adjuvant radiation therapy for colon cancer.
AB  - Post-operative radiation therapy has been used in selected patients with colon
      cancer. In contrast with rectal cancer, the primary failure pattern in colon
      cancer is abdominal. Local failure does occur, but is less frequent and more
      difficult to detect. Retrospective data suggest a benefit from local/regional
      radiation therapy on local control and disease-free survival in subsets of
      patients compared to historical controls. An ongoing phase III intergroup trial
      (INT 0130) will determine if local/regional radiation therapy improves the
      results of chemotherapy in subsets of patients with high-risk colon cancer. In
      general, the results of whole abdominal radiation plus 5-fluorouracil (5-FU) have
      been disappointing. However, the more recent data from the Southwest Oncology
      Group pilot trial are encouraging. In contrast to rectal cancer, where adjuvant
      chemotherapy plus radiation therapy is standard treatment in high-risk patients,
      the use of radiation therapy (either local/regional or whole abdomen) in colon
      cancer remains investigational.

PMID- 8556717
TI  - Primary central nervous system lymphoma in immunocompetent patients.

PMID- 8556718
TI  - Chemotherapy in locally advanced head and neck cancer: a critical reappraisal.

PMID- 8556720
TI  - The sexual sequelae of testicular cancer.

PMID- 8556719
TI  - Docetaxel (Taxotere): single agent activity, development of combination treatment
      and reducing side-effects.
AB  - Docetaxel is a new semi-synthetic taxoid, which acts as an antimicrotubule agent
      and is now clinically available. Clinical studies of docetaxel as a single agent
      and in combination with other cytotoxic drugs reveals favourable response rates
      in a number of solid tumor types. Docetaxel appears to have great potential in
      advanced breast cancer as first or secondline chemotherapy. The dose-limiting
      toxicity is an early and short-lasting neutropenia. Fluid retention is a
      cumbersome, sometimes disabling, side-effect. Other side-effects are usually mild
      and include alopecia, myalgia, mucostitis, neuropathy, hypersensitivity reaction,
      nail changes and cutaneous reactions.

PMID- 8556721
TI  - CT and MRI aspects of supratentorial hemispheric tumors of childhood and
      adolescence.
AB  - The neuroradiological features of supratentorial hemispheric tumors (SHTs) were
      studied in 27 patients whose ages ranged from 11 months to 18 years. Astrocytomas
      constituted 10 of the 27 SHTs. On computed tomography low-grade astrocytomas were
      in most cases hypodense; after intravenous administration of contrast medium,
      pilocytic astrocytomas enhanced, whereas fibrillary astrocytomas did not. Gd-DPTA
      enhanced magnetic resonance imaging was the most useful technique for the
      assessment of recurrences. Atypical imaging features were observed in one
      glioblastoma and in oligodendrogliomas (in half of the cases no calcifications
      were found). Gangliogliomas were surprisingly rather frequent in our series
      (5/27) and appeared in three cases as low-density, well-circumscribed lesions,
      not calcified and without edema and mass effect, while in two cases they had
      pronounced perifocal edema without clear demarcation. A rare desmoplastic
      infantile ganglioglioma was observed. The two meningiomas showed malignant
      behavior.

PMID- 8556722
TI  - Supratentorial interhemispheric cysts associated with callosal agenesis: surgical
      treatment and outcome in 16 children.
AB  - Cerebrospinal-fluid-filled interhemispheric cysts associated with callosal
      agenesis are relatively rare lesions, and have been subject to a varied and
      confusing terminology. From a pragmatic surgical point of view, we believe that
      the dorsal III ventricular cyst [35] and the giant interhemispheric cyst [23],
      although of different embryological origin, can be classified as one group. The
      most important condition that must be distinguished from interhemispheric cysts
      is the alobar form of holoprosencephaly. We describe the clinical symptomatology
      in 16 children who were surgically treated with a cysto-peritoneal shunt. The
      outcome, both neurologically and developmentally, was good in the large majority
      of cases, and compared favorably to similar cases in the older literature. It
      therefore seems reasonable, at the present state of knowledge and until further
      studies clarify the origin and natural history of these cysts, to treat them as
      early as possible in order to prevent gross developmental deficits.

PMID- 8556723
TI  - Preoperative chemotherapy with carboplatin alone in high risk medulloblastoma.
AB  - Few studies have been carried out regarding preoperative chemotherapy utilized in
      the treatment of primitive neuroectodermal tumors/medulloblastomas (PNET/MB). In
      this paper, the authors report 3 cases of children under three years of age, with
      a presumed diagnosis of PNET/MB, who were preoperatively treated with
      chemotherapy consisting of high doses of carboplatin alone. The treatment
      improved the childrens' clinical condition prior to surgery and facilitated tumor
      removal, resulting in partial regression of the tumor. The preoperative single
      drug therapy did not affect the histological diagnosis or prevent the presence of
      an effective degree of tumor sensitivity to the drug. All three children are
      still disease-free, after a mean follow-up period of 42 months.

PMID- 8556724
TI  - Pediatric cerebellar hemorrhages.
AB  - Cerebellar hemorrhage is a devastating condition with morbidity and mortality
      related not only to the etiology of the hemorrhage, but also to the timing of the
      intervention. Sixteen consecutive pediatric patients with acute cerebellar
      hemorrhages are presented: 6 had vascular abnormalities, 3 had tumors, and 2 had
      hemorrhages of unknown etiology. Thirteen of the 16 patients survived with only 1
      of the 13 having persistent vegetative state as a neurologic outcome. Six of 8
      patients presenting in a moribund condition had good outcomes, and 3 of 4
      patients presenting with fixed and dilated pupils also had good outcomes. Thus,
      in contrast to adults, rapid evaluation by CT scanning, followed by the judicious
      use of ventricular drainage and prompt surgical treatment, have resulted in
      favorable outcomes in pediatric patients despite their poor clinical
      presentations. None of the neonates having cerebellar hemorrhages required
      surgical intervention; their courses could be followed clinically and with
      transfontanel ultrasound.

PMID- 8556725
TI  - Regional cerebral hemodynamics in childhood moyamoya disease.
AB  - Regional cerebral blood flow (rCBF) and its reactivity to acetazolamide were
      analyzed in a series of 15 cases of childhood moyamoya disease, using the xenon
      133 inhalation method and single photon emission CT (SPECT). Most of the patients
      had normal mean hemispheric cerebral blood flow (mCBF), comparable to that of age
      matched healthy children. However, they had abnormal rCBF distribution and
      disturbed reactivity to acetazolamide in the territory of the internal carotid
      artery, especially in the frontal lobe. Surgical revascularization for the
      anterior circulation, which consisted of STA-MCA anastomosis and indirect
      synangiosis, dramatically improved these cerebral hemodynamics in the anterior
      circulation, including the frontal lobe, and reactivity to acetazolamide in the
      whole brain. These results suggest that surgical revascularization for the
      anterior circulation should be carried out in order to improve cerebral
      hemodynamics as widely as possible, especially in the frontal lobe, and may
      improve cerebral perfusion reserve in the posterior circulation.

PMID- 8556726
TI  - Clinical and angiographic follow-up of childhood-onset moyamoya disease.
AB  - To clarify the differences between childhood-onset moyamoya disease and that with
      onset in adulthood, we studied the clinical course and angiographic findings of
      adult patients (over 20 years of age) with moyamoya disease of childhood onset
      (up to 15 years of age). The clinical course in 25 patients could be assessed.
      The follow-up period was 5-27 years. Neurological deficits were noted in 11/23
      and mental disorders in 9/21. In all except one, the illness had started before
      the age of 7 years. Neither neurological nor mental condition changed during or
      after adolescence (15-20 years of age). Two patients died of intracranial
      hemorrhage. The disease progressed in angiographic stage until adolescence, but
      had stabilized or almost stabilized by the age of 20 years. This study indicates
      that moyamoya disease with onset in childhood carries high morbidity and
      mortality. The disease advances in angiographic stage between childhood and
      adolescence, but stabilizes or almost stabilizes between adolescence and
      adulthood.

PMID- 8556728
TI  - A cerebrospinal fluid shunt: a theoretical concept.
AB  - An innovative shunt design for the treatment of hydrocephalus is discussed. It is
      based on a two-tube configuration which restores accumulator function to suppress
      intracranial pressure fluctuations emanating from the brain and resulting from
      changes in the subject's postural position. Current shunt problems of
      overdrainage, occlusion, and infection are addressed and corrections inherent in
      the proposed design are described. Specific materials and characteristics for the
      construction of the proposed design are suggested.

PMID- 8556727
TI  - Value of transcranial Doppler indices in predicting raised ICP in infantile
      hydrocephalus. A study with review of the literature.
AB  - Cerebral hemodynamic changes in infants with progressive hydrocephalus have been
      studied with the transcranial Doppler (TCD) technique. Several authors have
      referred to the correlation between the hemodynamic changes and increased
      intracranial pressure (ICP). Despite conflicting conclusions on the value of
      pulsatility index (PI) and resistance index (RI) measurements for monitoring
      infantile hydrocephalus, these pulsatility indices are the most commonly used for
      this purpose. Although clinical signs of raised ICP are highly variable and
      unreliable in infants, assumptions have been made in most of the studies about
      the presence of elevated ICP on the basis of the patient's clinical state. Few
      studies have reported on actual ICP values, however, and a direct relationship
      between ICP and TCD changes has never been adequately demonstrated. In the
      present study, this relationship was investigated in long-term simultaneous
      TCD/ICP measurements, in an attempt to develop a noninvasive method of monitoring
      the effect of ICP on intracranial hemodynamics. Two groups of data sets were
      established. Group I consisted of pre- and postoperative (shunt implantation)
      TCD/ICP measurements. Group II were long-term simultaneous TCD/ICP recordings
      showing significant ICP variations. In most of the postoperative measurements
      there was a decrease in the average PI and RI values. The correlation between PI
      or RI and ICP in the long-term simultaneous recordings, however, was generally
      poor. The risk of obtaining false positive or false negative PI or RI values in
      short-term measurements was also demonstrated. It can be concluded from our
      results, besides the wide range of reference values for the Doppler indices and
      extracranial influences upon them, that the present Doppler indices are
      inadequate for monitoring the complex intracranial dynamic responses in patients
      with raised ICP.

PMID- 8556729
TI  - Amantadine treatment of a patient with anoxic brain injury.
AB  - An 18-year-old boy with anoxic brain injury, suffering from severe psychomotor
      inhibition, tetrarigidity and dystonia, was treated with amantadine in order to
      ameliorate his symptoms. Neuropsychological tests showed improvement in motor and
      cognitive functions.

PMID- 8556730
TI  - Nemaline myopathy: two autopsy reports.
AB  - Nemaline myopathy belongs to the group of congenital non-progressive myopathies;
      however, in rare cases death occurs in early infancy. We report two cases of
      rapidly fatal nemaline myopathy. The first patient, who died at the age of 26
      months, showed atrophy of type 1 fibers containing numerous rods in biopsy
      sections. Biopsy of the second patient, who had died at the age of 5 months,
      revealed severe maturational arrest and myopathy, but rods were so rare that
      diagnosis could only be made at the ultrastructural level. Autopsy of both
      patients showed that atrophy of type 1 fibers and maturational arrest had
      disappeared in the very same muscles; rods had moved to a central position in the
      first and significantly increased in number in the second case. Diaphragma
      muscles contained abundant amounts of rods in both cases. The cardiac musculature
      showed a few rods only in the first patient, who had developed heart
      insufficiency 11 months prior to death. Immunohistochemical analysis showed that
      rods did not contain desmin or ubiquitin.

PMID- 8556731
TI  - Synthesis of model glycolipids having two long alkyl chains.

PMID- 8556732
TI  - The crystal structure of methyl beta-cellotrioside monohydrate 0.25 ethanolate
      and its relationship to cellulose II.
AB  - The crystal structure of methyl beta-cellotrioside (methyl O-beta-D
      glucopyranosyl-(1-->4)-O-beta-d_guycopyranosyl-(1-->4)-be ta-D- glucopyranoside)
      complexed with water and ethanol, C19H34O16. H2O.0.25[C2H6O] was determined by
      combining Cu K alpha X-ray and synchrotron data collected at room temperature.
      The crystals have the monoclinic space group P21 with Z = 8 and unit cell
      parameters a = 7.9978(11), b = 76.38(4), c = 8.9908(6) A and beta = 116.40(1)
      degree. The structure, which was solved by direct methods and refined to a final
      R-factor of 0.067, contains four independent molecules of methyl beta
      cellotrioside with an extended conformation. They are arranged parallel to the
      long b axis of the unit cell, and organized in two pairs of antiparallel
      molecules. Each beta-D-glucopyranosyl residue of the four independent molecules
      is in the 4C1 pyranose conformation, and each (O-6) primary hydroxyl group has
      the gt conformation. The crystal structure of methyl beta-cellotrioside has many
      points in common with that of cellotetraose hemihydrate as well as with the
      structure of cellulose II. Thus, it is likely that the precise atomic coordinates
      obtained in this study can be directly transposed to give an improved structure
      for cellulose II where, in particular, only the gt conformation would be present
      at the primary hydroxyl groups of both polysaccharide chains.

PMID- 8556733
TI  - Synthesis of 2- and 4-nitrophenyl beta-glycosides of beta-(1-->4)- D-xylo
      oligosaccharides of dp 2-4.
AB  - 2- and 4-Nitrophenyl beta-D-xylopyranosides (4 and 5) were transformed, via
      dibutyltin oxidemediated acylation, into the corresponding 2,3-di-O-benzoyl
      derivatives 11 and 15. Xylobiose and xylotriose were easily isolated by charcoal
      column chromatography from a commercially available material and converted into
      the di- and trisaccharide methyl 1-thio-beta-glycosides 36 and 37. The 2-and 4
      nitrophenyl beta-glycosides of the beta-(1-->4)-D-xylo-oligosaccharides of dp 2-4
      were synthesized by N-iodosuccinimide-silver triflate-promoted condensation using
      11 and 15 as the glycosyl acceptors and ethyl 1-thio-beta-D-xylopyranoside
      triacetate 16, 36, and 37 as the glycosyl donors. Also described are an improved
      preparation of 4 and 5, and the synthesis of 1-naphthyl beta-D-xylopyranoside, as
      well as an alternative approach to the 2- and 4-nitrophenyl beta-xylobiosides.

PMID- 8556734
TI  - Structure of the Hafnia alvei strain PCM 1188 O-specific polysaccharide.
AB  - The lipopolysaccharide was extracted from cells of Hafnia alvei PCM 1188 strain
      and, after mild acid hydrolysis, the O-specific polysaccharide isolated and
      characterized. On the basis of sugar and methylation analysis, FAB mass
      spectrometry and NMR spectroscopy of the polysaccharide and oligosaccharides
      obtained after Smith degradation, or solvolysis with anhydrous hydrogen fluoride,
      the repeating unit of the O-specific polysaccharide was shown to be the
      pentasaccharide: [formula: see text]

PMID- 8556735
TI  - Molecular weight manipulation of chitosan. I: Kinetics of depolymerization by
      nitrous acid.
AB  - The kinetics of the depolymerization of chitosan in dilute aqueous HCl solutions
      by nitrous acid were studied. The rate of depolymerization is independent of the
      molecular weight of chitosan, first order with respect to the concentrations of
      both nitrous acid and glucosamine moieties, not catalysed by either hydrogen or
      chloride ions, and Arrhenius temperature dependent. Chitosan exhibits
      significantly decreased reactivity as the degree of deacetylation of the polymer
      increases. These results are consistent with a depolymerization reaction
      mechanism in which the rate-limiting step is nitrosation of the unprotonated
      amine by nitrous acidium ion.

PMID- 8556736
TI  - Structure of the O-specific side chain of the Escherichia coli O128
      lipopolysaccharide.
AB  - The O-specific polysaccharide isolated from Escherichia coli O128
      lipopolysaccharide contains D-galactose, L-fucose, and 2-acetamido-2-deoxy-D
      galactose in the molar ratios 2:1:2. The primary structure of the O-specific
      polysaccharide from E. coli was established by compositional analysis,
      methylation analysis, together with 1H and 13C NMR spectroscopy including two
      dimensional shift-correlated and one-dimensional NOE spectroscopy. The
      polysaccharide moiety was found to consist of a tetrasaccharide backbone
      containing D-galactose and 2-acetamido-2-deoxy-D-galactose, with L-fucose as a
      side chain in a branched pentasaccharide repeating unit having the following
      structure: [formula: see text]

PMID- 8556737
TI  - Metabolism of xyloglucan generates xylose-deficient oligosaccharide subunits of
      this polysaccharide in etiolated peas.
AB  - Oligosaccharide subunits of xyloglucan were isolated from the stems and roots of
      etiolated pea plants and structurally characterized. The two most abundant
      subunits of pea xyloglucan are the well-known nonasaccharide, XXFG, and
      heptasaccharide, XXXG. In addition, significant amounts of oligosaccharides that
      have not previously been reported to be subunits of pea xyloglucan were detected,
      including a decasaccharide, XLFG, two octasaccharides, XLXG and XXLG, a
      pentasaccharide, XXG, and a trisaccharide, XG. Several novel oligosaccharide
      subunits, including the octasaccharide, GXFG, and the hexasaccharide, GXXG, were
      also found. Xyloglucan oligosaccharides generated by treatment of intact pea stem
      cell walls were compared to oligosaccharides generated by endoglucanase treatment
      of xyloglucan polysaccharides obtained by subsequent alkali extraction of the
      same cell walls. The results suggest that the xyloglucan in etiolated pea stems
      is distributed between at least two domains, one of which is distinguished by its
      enzyme accessibility. We further hypothesize that the chemical modification of a
      xyloglucan during cell-wall maturation depends on its physical environment (i.e.,
      the domain in which it resides). For example, only the endoglucanase-released
      material, representing the enzyme-accessible xyloglucan domain, contains
      significant amounts of the two unusual oligosaccharide subunits, GXXG and GXFG,
      both of which have a nonreducing terminal glucosyl residue. This structure may be
      generated during cell-wall maturation by the sequential action of an endolytic
      enzyme (such as xyloglucan endotransglycosylase or endoglucanase) and an alpha
      xylosidase.

PMID- 8556738
TI  - Chemoenzymatic synthesis of 6 omega-S-alpha-D-glucopyranosyl-6 omega
      thiomaltooligosaccharides: their binding to Aspergillus niger glucoamylase G1 and
      its starch-binding domain.
AB  - A coupling reaction of cyclodextrin glucosyltransferase (CGTase) with glucose and
      6-deoxy-6-iodo-cyclomaltoheptaose (1), in the presence of glucoamylase, followed
      by acetylation, led to a convenient synthesis of acetylated 6III-deoxy-6III-iodo
      maltotriose (2) and 6IV-deoxy-6IV-iodomaltotraose (3). Nucleophilic displacement
      of the iodine atom of these protected maltotriose and maltotetraose analogs by
      the activated form of 2,3,4,6-tetra-O-acetyl-1-S- acetyl-1-thio-alpha-D-glucose
      (4) afforded peracetylated 6III-S-alpha-D-glucopyranosyl-6III-thiomaltotriose (5)
      and 6IV-S-alpha-D-glucopyranosyl-6IV-thiomaltotetraose (6) in high yield. The
      interaction of OH-free tetra- and penta-saccharides (7 and 8) with both
      glucoamylase G1 from Aspergillus niger as well as its isolated starch-binding
      domain fragment were studied by UV difference spectroscopy. It was found that the
      starch-binding domain has higher affinity for 7 and 8 than for maltotetraose and
      maltopentaose.

PMID- 8556739
TI  - Deprotection of p-methoxyphenyl pyranosides by anodic oxidation.

PMID- 8556740
TI  - Synthesis of the 2-deoxy analogue of the methyl alpha-glycoside of the
      monosaccharide repeating unit of the O-polysaccharide of Vibrio cholerae O:1.

PMID- 8556741
TI  - Convenient preparation of monoacylated beta-cyclodextrin (cyclomaltoheptaose) on
      the secondary hydroxyl side.

PMID- 8556742
TI  - A facile synthesis of alpha-D-galactopyranosyl-(1-->1)-alpha-D-galactopyranoside
      and its analogues.

PMID- 8556743
TI  - NMR reinvestigation of the capsular K27 polysaccharide (K27 antigen) from
      Escherichia coli O8:K27:H-.

PMID- 8556744
TI  - Evaluation of a fortnightly school-based sodium fluoride mouthrinse 4 years
      following its cessation.
AB  - The aim of this study was to investigate the effectiveness of a school-based
      fortnightly 0.2% sodium fluoride mouthrinse programme after children ceased to
      participate. The programme, which commenced at age 6 and ceased at age 12, was
      investigated 4 years following its cessation. Three groups of 12-year-olds and
      three groups of 16-year-olds were examined, i.e. children who had participated in
      the mouthrinse, those attending non-participating nearby schools and life-time
      residents of a fluoridated community. Significant differences in mean DMFT in the
      12-year-olds between the mouthrinse and the control group were not found in the
      16-year-old group. Mean DMFT for the mouthrinse group and those in a fluoridated
      community (which were the same in 12-year-olds) showed a statistically
      significant difference in those aged 16. Most caries found, both in 12-year-olds
      and in 16-year-olds, occurred on molar teeth and was found on pit and fissure
      surfaces. The cessation of these programmes at age 12 should be reappraised and
      the combination of school-based fluoride mouthrinse programmes with a fissure
      sealing programme is recommended.

PMID- 8556745
TI  - Effect of a modified toothpaste technique on approximal caries in preschool
      children.
AB  - A 3-year, double-blind caries trial was conducted to evaluate the caries-reducing
      effect of a modified technique to use toothpaste. At the outset, 369 children, 4
      years of age, were randomly assigned to four groups. At the end of the study,
      when the children were 7 years old, 281 (76%) had completed the trial. Two of the
      groups (test groups, n = 131) were given the following instructions regarding
      'toothpaste technique': (1) to spread the paste evenly on the teeth prior to
      brushing, (2) not to expectorate more than necessary during brushing, (3) to
      filter the remaining dentifrice foam in the dentition, together with a sip of
      water, by active cheek movements for 1 min before expectorating, and (4) not to
      carry out any further water rinsings afterwards, and not to eat or drink for 2 h
      after brushing. The children in the other two groups (control groups, n = 150)
      were not given any instruction how to use the dentifrice and how to rinse after
      the brushing, but were, as the children in the test groups, encouraged to use the
      test dentifrice and to brush their teeth twice daily. Two commercial fluoride
      dentifrices (A and B) were compared: one of the test groups and one of the
      control groups used each product. Approximal carious lesions were scored on bite
      wing radiographs at baseline and at the end of the study on the distal surface of
      the first and on the mesial surface of the second primary molars. No difference
      in caries increment was found between toothpastes A and B. The children in the
      two test groups developed a mean of 1.14 new dfs during the 3 years compared to
      1.55 in the two control groups (p < 0.05). Thus, the results indicate that the
      modified toothpaste technique reduced approximal caries in preschool children by
      an average of 26%.

PMID- 8556746
TI  - Plaque composition, fluoride tolerance and acid production of mutans streptococci
      before and after the suspension of the use of fluoride toothpastes.
AB  - Although fluoride toothpastes are widely used for caries prevention, little is
      known about the impact of fluoride dentifrices on plaque composition. Also the
      issue of adaptation of mutans streptococci to grow in vivo in a fluoride
      environment has received little attention. Such an adaptation may be of interest
      as it has been suggested that adapted mutans streptococci may show reduced
      glycolytic activity thereby being less cariogenic. In the present experiments the
      impact of the suspension of the use of fluoride toothpastes on plaque
      composition, fluoride tolerance and acid production of mutans streptococci was
      studied. Pooled plaque samples from the lingual surfaces of the lower incisors
      were collected from individuals (n = 13) just before and 7 weeks after they had
      replaced their fluoride toothpastes (0.1-0.15% F) with a non-fluoride one. The
      samples were analysed for fluoride and the numbers and proportions of
      streptococci, Streptococcus mutans, Streptococcus sobrinus, Actinomyces species,
      and lactobacilli, respectively. The fluoride tolerance of the mutans streptococci
      was estimated by culture of the plaque samples on TYCSB agar supplemented with of
      0, 1, 2, 3, 4, and 5 mmol/l fluoride (NaF) at pH 7.2. From each plaque sample six
      S. mutans strains were isolated for the measurement of the rate of acid
      production (Vap) at pH 7 in the presence of 0, 5, and 10 mmol/l F. The overnight
      final pH was measured in cultures of the S. mutans strains with excess of glucose
      and 0, 5, and 10 mmol/l F. The results showed that the removal of the fluoride
      pressure from plaque did not affect the numbers or proportions of the various
      species and genera of bacteria. The fluoride tolerance of the mutans
      streptococci, and the Vap or the overnight final pH of the isolated strains had
      not changed. These results suggest that the use of fluoride toothpaste had not
      affected plaque composition, nor fluoride tolerance or acidogenicity of mutans
      streptococci. Probably the amount of fluoride delivered by fluoride dentifrices
      to dental plaque is too low to induce such adaptations.

PMID- 8556747
TI  - Caries development in children from 2.5 to 3.5 years of age: a longitudinal
      study.
AB  - The development of dental caries from the age of 2.5 to 3.5 years was studied
      longitudinally in 692 children living in the southern suburbs of Stockholm. The
      parents answered a structured questionnaire concerning the family's social and
      immigrant background as well as the dietary habits, oral hygiene and fluoride
      exposure of their children. Furthermore, the occurrence of mutans streptococci
      and lactobacilli was determined in samples taken from the tongue of the children,
      and the buffer capacity of the saliva was measured. At baseline examination,
      11.3% of the children exhibited dental caries. At follow-up, 1 year later,
      decayed and/or filled surfaces were registered in 36.7% of the subjects. The
      majority of the new lesions were located on the occlusal surfaces of the second
      molar. Ninety-two percent of the children with caries at baseline developed new
      carious lesions during the 1-year period, compared to 29% of the children who
      were caries-free at baseline (p < 0.001). Of the lesions diagnosed at baseline as
      initial caries, 64% progressed to manifest lesions during the 1-year period. The
      study indicates that children with early caries development exhibit high caries
      progression as well as a high risk for further development of an extensive number
      of new carious lesions.

PMID- 8556748
TI  - Evaluation of the in vitro cariogenic potential of Streptococcus mutans strains
      isolated from 12-year-old children with differing caries experience.
AB  - The limited usefulness of caries activity tests based solely on counts of mutans
      streptococci has been recognised increasingly. Such tests do not account for
      potential differences in cariogenicity of Streptococcus mutans strains harboured
      by individual patients. Hence, this study describes the evaluation of a simple
      and inexpensive method involving the dissolution of powdered hydroxyapatite as a
      means of determining the cariogenic potential of 64 freshly isolated strains of
      S. mutans from 24 children. Whilst it is apparent that differences between
      strains isolated from individuals could be demonstrated using this test, the
      variability observed was such that it was not possible to relate in vitro
      cariogenicity to actual clinical caries experience.

PMID- 8556749
TI  - Do caries explorers transmit infections with persons? An evaluation of second
      molar caries onsets.
AB  - Dental caries explorers may become contaminated during routine caries
      examinations with pathogenic organisms and thereby potentially transmit
      infections from one tooth to another within a patient. The purpose of this study
      was to test the hypothesis that the contamination status of explorers influenced
      the caries risk of second molars. Two explorer contamination statuses were
      defined: (1) contamination status 1--explorers which had probed a carious molar
      just prior to examining the second molar, and (2) contamination status 2--sterile
      explorers versus explorers which had probed several teeth. Caries examinations
      were performed by 4 dentists on a cohort of 4th grade students in Belize City.
      The examination dates and sample sizes (n) were: September-October 1989 (n =
      1,277), January 1991 (n = 1,111), and January 1992 (n = 961), and January
      February 1993 (n = 861). Within this cohort, there were 221 subjects who (1) had
      at least one pit and fissure carious onset on a caries-free second molar, (2) had
      no evidence of dental treatments, and (3) were examined by the same examiner
      during the entire study. After adjusting for confounding variables, the
      examination of a second molar with a dental caries explorer in either
      contamination status 1 or 2 had no substantial effect on the caries risk (rate
      ratio 0.95, 95% confidence interval: 0.77-1.18, and rate ratio 1.18, 95%
      confidence interval: 0.89-1.56, respectively). If a true rate ratio of 1.7 or
      greater was associated with the contamination status 1 and 2, these analyses had
      more than 99 and 80% probability of detecting it, respectively. CONCLUSIONS:
      Examining a sound second molar with a contaminated dental explorer either does
      not affect the caries risk, or results in such a small increase in caries risk
      that it can only be reliably identified in studies where the exposure of sound
      teeth to contaminated dental explorers is randomized.

PMID- 8556750
TI  - Site specificity of citric acid retention after an oral rinse.
AB  - Erosion of the buccal incisor enamel, most frequent in the upper jaw, has been
      associated with excessive oral exposure to citric acid-containing foodstuffs. The
      aim of the study was to determine the retention of citric acid at different sites
      in the mouth after a standardized exposure. Thirty-four normal subjects rinsed
      with 95.2 mmol/l (2%) citric acid, pH 2.1, for 5 s. At 1 min 55 s after the rinse
      a preweighed cotton pellet was used to collect saliva samples from upper labial
      incisor surfaces (UB), lower labial incisor surfaces (LB) and sublingually (SL).
      The citric acid concentration was determined enzymatically. The concentrations
      were (mean +/- SD): 32.12 +/- 19.50, 11.90 +/- 8.60 and 1.52 +/- 1.90 mmol/l in
      the saliva collected from the UB, LB and SL sites, respectively. Analysis of
      variance revealed that the citric acid concentration in the upper incisor site
      differed significantly from that of the lower incisor site (p < 0.001) and the
      sublingual site (p < 0.001), and that the lower incisor site differed
      significantly from the sublingual site (p < 0.001). The individuals differed
      significantly with respect to citric acid retention (p < 0.05). A significant
      correlation was found between UB and LB sites (r = 0.61, p < 0.05).

PMID- 8556751
TI  - An investigation into the ability of soft drinks to adhere to enamel.
AB  - Loss of enamel due to dietary causes, either by acid erosion or the fermentation
      of dietary sugars, is well known. These processes will be affected by a number of
      factors, one of which is the ability of the food to adhere to the enamel. The aim
      of this study was to determine the thermodynamic work of adhesion of a number of
      soft drinks to enamel. The results indicated significant differences in the
      ability of various drinks to adhere to enamel in vivo. In addition to obtaining a
      ranking of the drinks under test, the likelihood of them being displaced by
      saliva was considered.

PMID- 8556752
TI  - The effect of sucrose-containing chewing-gum use on in situ enamel lesion
      remineralization.
AB  - Two independent cross-over studies have now been carried out to evaluate the
      effect of a regime of chewing sucrose-containing gum on enamel lesion
      remineralization. The first study has been reported in detail elsewhere. This
      further study aimed to increase the data set with an additional 13 volunteers.
      Similar protocols were followed in both studies. Weighted averages from the two
      studies showed delta z values corresponding to 16.8% remineralization for the gum
      versus 11.6% remineralization for the control (p = 0.046, two-sided). A
      significant difference between test and control was evident for lesion body (p =
      0.0004, two-sided) but not for surface zone (p = 0.32, two-sided).

PMID- 8556754
TI  - Effect of various surfactants and aluminum solutions on in vitro acid dissolution
      of dental enamel.
AB  - Various surfactants were investigated for compatibility and stability in aqueous
      dispersions with aluminum (Al) and for their ability to inhibit enamel acid
      dissolution both with and without Al present. A total of 39 samples, representing
      anionic, cationic and nonionic surfactant classes, were dispersed at a
      concentration of 1% in water or a 0.005 mol/l AlK(SO4)2 solution. After 24 h the
      dispersions were evaluated for visual appearance, pH and ability to reduce enamel
      acid dissolution (EDR). Because reactions involving Al are sometimes very slow to
      equilibrate, the surfactants that were compatible with Al and did not suppress
      the 80% EDR of the Al solution were tested again after storage for 12 months.
      Most surfactant samples formed limpid aqueous dispersions that had little or no
      EDR activity. However, there were substantial differences in the effect of
      surfactants on Al EDR activity. Under the conditions of this study, nonionic
      samples from every subclass were compatible with Al. Anionics usually resulted in
      the formation of insoluble products that inactivated Al, although a polyethoxy
      carboxylate and a sulfated ester were exceptions which formed clear, stable
      dispersions that yielded high EDR values. The cationics varied in their response
      to Al; the amines reacted with and deactivated Al, but quaternary ammonium
      compounds were more compatible. No surfactants from any class enhanced the
      capacity of Al to reduce enamel acid dissolution. The long-term stability data
      revealed that 21 of 22 Al-surfactant combinations tested retained a significant
      EDR activity. However, some dispersions exhibited visual signs of instability,
      and the pH of many nonionic samples decreased. This study showed that, in the
      presence of Al, nonionic surfactants were relatively stable for long periods and
      did not block the ability of Al to inhibit enamel acid dissolution. However,
      certain anionic and cationic surfactants also displayed comparable properties.

PMID- 8556753
TI  - Effect of lactic acid and proteolytic enzymes on the release of organic matrix
      components from human root dentin.
AB  - The mechanisms of organic matrix breakdown in the root caries process are not
      well understood. Therefore, the combined and separate effects of lactic acid and
      proteolytic enzymes on the degradation of human dentin collagen, glycoproteins,
      proteoglycans and phosphoproteins were investigated in the present study. Dentin
      powder was pretreated with lactic acid (pH 4.0), distilled and deionized (dd)
      water (pH 7.0) and EDTA/guanidine HCl (pH 7.4) for 24 h. Pellets of acid- or dd
      water-pretreated dentin powder were washed, dried, and then treated with trypsin,
      bacterial or mammalian tissue collagenase, or control buffer for 3 h. The
      released dentin proteins were analyzed by reducing sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and immunoblotting to identify degraded type I
      collagen, proteoglycans, glycoproteins and phosphoproteins. All water and acid
      pretreatment and enzyme treatment groups demonstrated two collagen fragment bands
      with molecular weights at approximately 79 kD. Further studies showed that the 79
      kD proteins from acid-pretreated dentin collagen were degraded by tissue
      collagenase, suggesting that endogenous collagenase may be involved in the
      degradation of root dentin collagen. Dentin proteoglycans were detectable in all
      the treatment groups by protein slot blotting. Relatively few distinct
      glycoproteins and proteoglycans, and no phosphoproteins were detected by
      immunoblotting. Results from this study suggest that both acids and proteolytic
      enzymes from either host or microbial origin are important in the degradation of
      human dentin matrix and the mechanisms involved in the release of various
      noncollagenous proteins may be different.

PMID- 8556755
TI  - The effect of milk and kappa casein on streptococcal glucosyltransferase.
AB  - Many dietary components such as carbohydrates, lipids and proteins may be
      incorporated into the salivary pellicle and thus may affect glucosyltransferase
      (GTF) activity on pellicle surfaces. The effect of milk on streptococcal GTF
      activity was determined. Milk, when coated onto buffer-coated hydroxyapatite or
      saliva-coated hydroxyapatite (sHA), reduced the subsequent adsorption of GTF onto
      the surfaces. Milk also reduced the expression of enzymatic activity of GTF
      adsorbed onto sHA. kappa-Casein, when present on the surface of sHA, reduced the
      adsorption of GTF activity onto sHA, resulting in reduced glucan formation. alpha
      Casein had no effect on the adsorption of GTF onto sHA or on subsequent glucan
      formation. Both milk and kappa-casein reduced activity of the enzyme in solution.
      The presence of milk and kappa-casein fractions on the surface of sHA and in
      solution with GTF can clearly modulate glucan formation in vitro.

PMID- 8556756
TI  - Adherence of microorganisms to rat salivary pellicles.
AB  - Numerous studies, using models to mimic the formation of the acquired pellicle,
      have concentrated on human saliva-coated hydroxyapatite; in contrast, although
      the rat is frequently used as an animal model, the information concerning the
      formation of pellicles from rat saliva is sparse. We compared the ability of
      Streptococcus and Actinomyces species to adhere to hydroxyapatite coated by rat
      saliva (rsHA) and human saliva (sHA). We also explored the influence of glucan
      synthesized in situ on the adherence of organisms. We show that each strain of
      organism has a distinct binding pattern, which was essentially the same with
      surfaces coated with either rat or human saliva. Dissolved rsHA beads revealed a
      major protein band (35-49 kD), identified as glutamine/glutamic-acid-rich
      protein; acidic proline-rich protein (31-45 kD and alpha-amylase (66 kD) were
      also identified. Overall, these in vitro data strongly suggest that the
      principles of bacterial adhesion to rsHA are similar to those observed with sHA.

PMID- 8556757
TI  - Ultrastructural change of enamel exposed to a normal pulsed Nd-YAG laser.
AB  - The ultrastructural changes of the enamel surface occurring due to normal pulsed
      Nd-YAG laser irradiation were examined by scanning electron microscopy. The
      melted and recrystallized enamel in the lased enamel surface was observed. A
      coalescence of enamel globules was caused by 10 pulses of laser irradiation. In
      the case of excessively repeated irradiation (3 applications of 10 pulses), new
      particles of enamel crystal were produced which had a larger size than the
      original and measured about 0.2-1.0 microns in diameter. In some portions, large
      sized hexagonal particles were also observed. In fractured surfaces of enamel,
      the shapes of the new particles of enamel crystal varied and included granules,
      needles and columns. The column structure had various appearances such as being
      well packed, along with piled granules and hollow columns, as well as having
      intercrystal or intracrystal voids. It was suggested that a distinctive polygonal
      column shape of more than 2 microns in length might be formed in the process of
      homogeneous melting at high temperatures followed by uniform cooling and
      contraction. The recrystallized layer demonstrated significant acid resistance
      but was a little fragile. These results greatly support the hypothesis that a
      larger crystal size may cause acid resistance in enamel exposed to pulsed laser.

PMID- 8556758
TI  - [Risk factors in carcinoma of the prostate].
AB  - The authors review risk factors of prostate carcinoma. Generally accepted factors
      include advanced age; some work confirms a familial incidence of the condition.
      When the incidence is evaluated by race, the highest prevalence is described in
      American negroes and the lowest prevalence in the Japanese. The higher prevalence
      in northern areas and lower prevalence in southern areas is explained by the
      effect of ultraviolet radiation. It is generally accepted that prostate carcinoma
      depends on androgens; the dependence on sexual activity is evaluated in relation
      to the higher androgen concentration and the higher risk of infection. As to
      dietary factors the condition is promoted by fats; the higher prevalence in
      smokers can be explained by the cadmium and nickel content of cigarettes. With
      regard to occupation, brain workers are affected more frequently; as to
      occupational carcinogens cadmium and nickel are quoted most frequently.

PMID- 8556759
TI  - [Thoracic electric bioimpedance].
AB  - So far there was, no simple non-invasive method for the assessment of the minute.
      Rheoplethysmographic methods developed in the seventies did not give reliable
      results. The submitted paper presents a new quantitative rheople-thysmographic
      method - thoracic electric bioimpedance. The authors explain the technique,
      defines the assessed parameters and evaluates their scatter according to data
      reported in the literature. They explain from the physiological aspect the
      possible development of some errors when applying the method. The method of
      thoracic electric bioimpedance makes it possible to assess clinically valuable
      haemodynamic parameters comparable with corresponding values obtained by
      pretentious and invasive methods.

PMID- 8556760
TI  - [Use of autologous blood, plasma and thrombocyte concentrates in heart surgery].
AB  - BACKGROUND: The objective of the work was to assess whether autologous platelets
      will reduce haemorrhage after cardiac operations and the need of blood
      transfusions. METHODS AND RESULTS: From 34 patients in the course of 3 - 4 weeks
      before operation apheretically on average 935 ml fresh frozen plasma (FFP) were
      taken and two transfusion units (TU) of whole blood. In group A (13 patients, 9
      men and 4 women, aged 53 +/- 12 years) the blood losses during 24 hours after
      operation amounted to 982 +/- 589 ml and the total losses were 1,129 +/- 787 ml.
      It was necessary to administer 1.9 +/- 1.5 TU of homologous red cell concentrates
      and 5.0 +/- 2.9 TU of homologous FFP. Three patients (23%) did not need any
      homologous red cell concentrates and 2 (15%) did not need homologous FFP. In
      group B (21 patients, 14 men and 7 women, aged 55 +/- 14 years), there moreover
      one or two days before operation apheretically 2.6 +/- 0.5 x 10(11) platelets
      were withdrawn and 420 ml FFP, the blood losses within 24 hours were 581 +/- 201
      ml and the total losses 635 +/- 220 ml. It was necessary to administer 0.9 +/-
      1.3 TU homologous red cell mass and 2.2 +/- 2.1 TU homologous FFP. Eleven
      patients (52%) did not need a transfusion of homologous red cell concentrates and
      9 (43%) did not need homologous FFP. The differences in blood losses and
      transfusions of homologous preparations between groups ar statistically
      significant (p < 0.001). CONCLUSIONS: The use of autologous platelets reduces
      significantly blood losses and the need of transfusions of homologous
      preparations during operations on the heart.

PMID- 8556761
TI  - [Growth and adult height in patients with congenital adrenal hyperplasia].
AB  - BACKGROUND: The growth of children with congenital adrenal hyperplasia (CAH) can
      be impaired by overproduction of endogenous androgens which after the initial
      growth acceleration lead to early ossification of the growth plates and a low
      adult height, and by excessive glucocorticoid treatment as the latter antagonize
      the effect of growth hormone and cause growth retardation. In order to identify
      the life period decisive for the adult height of patients with CAH the authors
      analyzed retrospectively their growth data. METHODS AND RESULTS: In 35 children
      with 21-hydroxylase deficiency (24 girls, age 4.8 - 22.3 years and 11 boys, age
      6.3 - 22.3 years) the height and bone maturation was evaluated at the age of 3,
      7, 10 and 12 years and the adult height. In all girls and in 5/11 boys treatment
      of CAH was started at the age of 0.0 - 1.5 years (median 0.1) (early diagnosis),
      in 6/11 boys at the age of 4.5 - 7.0 years (median 5.2) (late diagnosis). In
      children with an early diagnosis growth retardation by the age of 3 years
      occurred (SDS of the girls' height' -1.4 +/- 0.2, n = 24, boys -0.7 +/- 0.4, n =
      5). The height deficit in girls at the age of 3 predicted significantly the loss
      of adult height, as compared with the expected height in the family (r = 0.68, p
      = 0.02). By the age of 7 years the height deficit declined insignificantly (SDS
      of girls' height -1.0 +/- 0.2, n = 21), but bone maturation proceeded rapidly (3
      years: SDS 0.1 +/- 0.4, n = 7, 7 years: SDS 1.4 +/- 0.5, n = 11). The adult
      height of girls (n = 12) is 147.0 - 162.5 cm (mean 156.7), i.e. -1.6 +/- 0.2 SDS,
      in early diagnosed boys (n = 4) 159 - 176.6 cm (mean 167.6), i.e. -1.7 +/- 0.5
      SDS, in boys with a late diagnosis (n =4) 165.0 - 172.0 (mean 169.5), i.e. -1.5
      +/- 0.3 SDS. CONCLUSIONS: In treated children with CAH growth retardation occurs
      already from the age of 3 years, apparently due to excessive glucocorticoid
      doses. This retardation predicts a loss of adult height. Between the age of 3 and
      7 years the growth prognosis deteriorates further due to accelerated bone
      maturation resulting from inadequate suppression of androgens. Optimal treatment
      during these periods in life can improve the prerequisites for attaining the
      predicted adult height.

PMID- 8556762
TI  - [The human genome--chromosome 21].
AB  - The 21st chromosome is probably known above all in conjunction with congenital or
      hereditary trisomy causing Down's syndrome. Its prevalence can be to a certain
      extent regulated by prevention, planned parenthood and examination during
      pregnancy. Particularly urgent for contemporary health services, more so in
      countries with a high mean age, are diseases such as e.g. Alzheimer's dementia,
      the AD1 locus of which is assumed to be on the 21st chromosome. The locus of the
      APP precursor of the protein beta-amyloid is suspected, as there in patients from
      affected families mutational changes were found. That a casual relationship could
      be involved is suggested also by results obtained in transgenic mice. As to other
      loci of the 21st chromosome, the author mentions aldo ALS1 for amyotrophic
      lateral sclerosis and EPMI for progressive myoclonic epilepsy.

PMID- 8556763
TI  - [Computer-assisted interpretation of laboratory results].
AB  - The clinician-the patient-the laboratory are parts of one communication system.
      Computer based communication between laboratory and clinician is fast, highly
      reliable, and accurate. Computer assisted interpretative reports are a natural
      consequence of the requirements of problem solving strategies in clinical and
      laboratory medicine.

PMID- 8556764
TI  - [Pain, suffering and loneliness in the aged].

PMID- 8556765
TI  - Ca2+ in visual transduction and adaptation in vertebrates and invertebrates.

PMID- 8556766
TI  - Phosphoinositide-mediated phototransduction in Drosophila photoreceptors: the
      role of Ca2+ and trp.
AB  - Drosphoinate photoreceptors, represent a paradigm for the genetic dissection of
      phototransduction and, more generally for Ca2+ signaling. As in most
      invertebrates, phototransduction in Drosophila is mediated by the
      phosphoinositide (PI) cascade and is completely blocked by null mutations of the
      norpA gene which encodes a phospholipase C-beta isoform. The light-activated
      conductance in Drosophila is normally highly permeable to Ca2+, but in null
      mutants of the trp gene Ca2+ permeability is greatly reduced. Furthermore, the
      trp gene sequence shows homologies with voltage gated Ca2+ channels, suggesting
      that trp encodes a light-sensitive channel subunit. Ca2+ influx via these
      channels is instrumental in light adaptation, and profoundly influences
      phototransduction via positive and negative feedback at multiple molecular
      targets including protein kinase C. The mechanism of activation of the light
      sensitive channels remains unresolved. A requirement for Ca2+ release from
      internal stores is suggested by the finding that Drosophila photoreceptors cannot
      sustain a maintained response under various conditions which might be expected to
      result in depletion of Ca2+ stores. However, Ca2+ release cannot be detected by
      Ca2+ indicator dyes and raising Ca2+ by photorelease of caged Ca2+ fails to mimic
      excitation. Recent studies, both in situ and with heterologously expressed trp
      protein, suggest that the trp-dependent channels may be activated by a process
      analogous to 'capacitative Ca2+ entry', a widespread, but poorly understood mode
      of PI-regulated Ca2+ influx in vertebrate cells.

PMID- 8556767
TI  - Rods, cones and calcium.
AB  - A transduction cascade in the outer segments of vertebrate photoreceptors
      amplifies the visual signal, resulting in the metabolism of cGMP and the closure
      of ionic channels. The intracellular calcium concentration declines after a light
      response, and this decline is the key regulator responsible for controlling the
      gain of the transduction cascade. Calcium turnover in the outer segment is
      determined by three processes: influx through light-sensitive channels; buffering
      within the outer segment; and extrusion by a Na/Ca,K exchange mechanism.

PMID- 8556768
TI  - Ca2+ flux in retinal rod and cone outer segments: differences in Ca2+ selectivity
      of the cGMP-gated ion channels and Ca2+ clearance rates.
AB  - In intact rod and cone photoreceptors of various vertebrate species,
      depolarization in the dark to > or = +20 mV specifically activates the cGMP
      dependent conductance in the outer segment. This activation reflects a voltage
      dependent decrease in cytoplasmic Ca2+ and the consequent activation of a Ca(2+)
      dependent guanylyl cyclase. The conductance activation in cones is much faster in
      time course and larger in extent than that in rods. Simulations of the
      experimental results suggest that these differences arise from differences in
      Ca2+ homeostasis in the rod and cone outer segments. Direct measurements
      demonstrate that, indeed, the Ca2+ permeability of the cGMP-gated channels is
      higher in cones than in rods. Also, as was previously known, the rate of Ca2+
      efflux from cone outer segments is higher than that in rods. Therefore, a given
      light-dependent change in membrane current should cause a much larger and much
      quicker decrease in Ca2+ concentration in cones than in rods. The activity of
      every Ca(2+)-dependent biochemical event in the outer segment should, hence,
      change more rapidly and to a larger extent in cones than in rods. We propose that
      these kinetic and stoichiometric differences in the function of Ca(2+)-dependent
      processes is important in explaining the difference in the transduction signal of
      the two receptor types.

PMID- 8556769
TI  - Light activated calcium release in Limulus ventral photoreceptors as revealed by
      laser confocal microscopy.
AB  - Using confocal imaging and fluorescent calcium indicators, light-induced
      elevation of intracellular Ca2+ concentration ([Ca2+]i) in Limulus ventral
      photoreceptors was shown to be initiated within 4 microns of the light-sensitive
      plasma membrane. Within 500 ms, elevation of [Ca2+]i spread throughout the light
      sensitive rhabdomeral lobe of the photoreceptor, but barely penetrated the
      arhabdomeral lobe. During saturating illumination of measurement spots near the
      plasma membrane, [Ca2+]i rose at rates of 1-2 mM/s after a latent period of 14-40
      ms, reaching peak concentrations of approximately 150 microM. Rapid elevation of
      [Ca2+]i persisted in the absence of extracellular Ca2+ and was therefore ascribed
      to release from intracellular stores. The elevation of [Ca2+]i was always
      detectable within 5 ms of the electrical response of the photoreceptor to light.
      In 14 out of 54 measurements, detection of elevated calcium preceded the
      electrical response. Cyclopiazonic acid, an inhibitor of endoplasmic reticulum Ca
      pumps, greatly reduced the elevation of [Ca2+]i during bright flashes and the
      sensitivity of the electrical response to dim flashes. However, the maximal
      response to bright flashes was not diminished. Therefore, although the calcium
      release that we detect may be fast enough to contribute to the electrical
      response we are unable to demonstrate that it is absolutely required.

PMID- 8556770
TI  - Control of photoreceptor proteins by Ca2+.
AB  - A decrease of cytoplasmic Ca(2+)-concentration in vertebrate photoreceptor cells
      after illumination is necessary for light adaptation. Although the mechanisms of
      adaptation is not completely understood, several Ca(2+)-dependent cellular
      processes have been discovered. Some involve calcium-binding proteins like
      recoverin, guanylyl cyclase-activating protein and calmodulin, and their target
      proteins rhodopsin kinase, guanylyl cyclase, the cGMP-gated channel, and NO
      synthase. The activity of several enzymes or channels is directly controlled by
      Ca2+ and does not involve calcium-binding proteins. These proteins are
      pyrophosphatase, protein kinase C and the cGMP-gated channel.

PMID- 8556771
TI  - Calcium homeostasis in vertebrate retinal rod outer segments.
AB  - The outer segments of vertebrate retinal rod photoreceptors (ROS) exhibit dynamic
      Ca2+ fluxes. In darkness, Ca2+ continuously enters via the light-sensitive, cGMP
      gated channels and this requires the presence of a powerful Ca2+ extrusion
      mechanism in the ROS plasma membrane. Our laboratory has characterized a Na/Ca+K
      exchanger in the ROS plasma membrane, which utilizes both inward Na+ gradient and
      outward K+ gradient to extrude Ca2+. Here, I review our work on the functional
      properties of the Na/Ca+K exchanger including the stoichiometry, ion binding
      sites and regulation of Ca2+ transport via Na/Ca+K exchange. Inactivation of the
      Ca2+ extrusion mode of the Na/Ca+K exchanger will be discussed as a mechanism to
      prevent lowering of cytosolic free Ca2+ to undesirably low values of < 1 nM that
      are expected from the coupling stoichiometry of the Na/Ca+K exchanger and that
      are expected to occur when Ca2+ influx via the cGMP-gated channels is interrupted
      during saturation of rod photoreceptors in bright light. This review also
      reexamines the contribution of internal Ca2+ stores (i.e. disks) to Ca2+
      homeostasis in ROS.

PMID- 8556772
TI  - Distinguishing between roles for calcium in Limulus photoreceptor excitation.
AB  - The role for Ca2+ in the excitation process by which light opens membrane
      channels in Limulus photoreceptors is discussed. Light initiates a phospholipase
      C/IP3 pathway that results in a rapid elevation of intracellular Ca2+, but
      whether this elevation is causal in triggering the light response or merely
      synergistic to some other second messenger pathway has been unclear. We have
      developed a procedure using progressive injection of Ca2+ buffers that
      distinguishes between mediation and synergy models [Shin J-H. Richard EA. Lisman
      JE. (1992) Ca2+ is an obligatory intermediate in the excitation cascade of
      Limulus photoreceptors. Neuron, 11, 845-855]. Our conclusion is that Ca2+
      mediates all phases of the light-response. Models of this kind had previously
      been rejected because intracellular injection of Ca2+ buffer can lead to an
      increase of the late component (> 200 ms) of the response to bright, sustained
      light. We have used computer simulations of IP3 mediated Ca2+ release to show
      that the positive and negative regulation of this process by Ca2+ itself together
      with other feedback loops can explain counterintuitive effects of Ca2+ buffers.

PMID- 8556773
TI  - Structure and cellular physiology of Ca2+ stores in invertebrate photoreceptors.
AB  - Invertebrate microvillar photoreceptors contain an extensive, morphologically
      continuous endoplasmic reticulum (ER) that comprises several distinct subregions.
      Most prominent is the smooth submicrovillar ER, a sponge-like cisternal network
      underneath the photoreceptive microvillar membrane. The submicrovillar ER
      spatially separates the microvilli and a narrow space of submicrovillar cytoplasm
      from the remaining cell body, and, thus, defines a transduction compartment. In
      bee and locust photoreceptors, the shape and position of these submicrovillar ER
      cisternae is maintained by interaction with actin filaments. The structural
      layout of the ER is either rather static, or, in some invertebrate species, the
      ER undergoes dramatic rearrangements during illumination. The submicrovillar ER
      has a high Ca content in dark-adapted cells (47.5 mmol/kg dry weight in bee
      photoreceptors), and acts as a source and sink for Ca2+ mobilized by
      illumination. About 50% of the Ca content is released by a 3 s, non-saturating
      light stimulus, and an almost equimolar amount of Mg is taken up to maintain
      electroneutrality within the ER. Ca2+ release is initiated by Ins(1,4,5)P3. In
      addition, the submicrovillar ER contains a heparin-insensitive, caffeine- and
      ryanodine-sensitive Ca2+ release pathway in bee photoreceptors. Both the
      Ins(1,4,5)P3-dependent and the ryanodine-sensitive Ca2+ release mechanism are
      modulated by cytosolic Ca2+, but at different Ca2+ concentrations. The presence
      of two release pathways with different Ca2+ sensitivities may be a prerequisite
      for highly localized, exceptionally fast and large Ca2+ elevations during the
      illumination of invertebrate photoreceptors.

PMID- 8556774
TI  - Acute myocardial infarction in Zimbabwe: the changing scene of coronary artery
      disease.
AB  - From 1988 to 1993 (six years), 127 suspected cases of acute myocardial infarction
      (AMI) were admitted to the Parirenyatwa Hospital coronary care unit. AMI was
      confirmed in 76 cases, 37 were Black, 27 White, six Indian and six Coloured. For
      Blacks the male to female ratio was 5:1. The clinical and laboratory features and
      complications of AMI were similar in all ethnic groups. Compared to other groups,
      Blacks presented to hospital late, an observation which has important
      implications for thrombolytic therapy. With the increasing number of cases of AMI
      now being seen among Black Zimbabweans, the time has come for the evaluation of
      the changing risk factor profile and the initiation of education and intervention
      programmes which could contain this rise before it spirals into a major health
      problem.

PMID- 8556775
TI  - Cholelithiasis in Dar es Salaam, Tanzania.
AB  - In a five year review, there were 30 cases of cholelithiasis treated at the
      Muhimbili Medical Centre, Dar es Salaam, Tanzania. The male to female ratio was
      1:3, and the peak age for cholelithiasis was in the 30 to 49 years age group.
      Right upper quadrant abdominal pain was the commonest presenting symptom (100
      pc), and cholecystectomy was performed in all patients. Local complications of
      gall stones were recorded in seven patients (23.3 pc) and these included; gall
      bladder empyema, pericholecysteal abscess, CBD stone, gall bladder adenoma, gall
      bladder mucocele, and two patients had acute cholecystis. Stones were multiple in
      90 pc of patients, and on macroscopic classification the ratio of cholesterol to
      pigment stones was 2:1. There was no death in this series of 30 patients.

PMID- 8556776
TI  - Zinc, hydrochlorothiazide and sexual dysfunction.
AB  - This study was designed to test the hypothesis that hydrochlorothiazide a
      diuretic used to treat hypertension depletes body zinc and thereby cause sexual
      dysfunction. Serum zinc and sexual dysfunction were measured in 39 middle aged
      hypertensive men who had been taking hydrochlorothiazide in average daily doses
      of between 25 and 50 mg daily for at least six months, and a control group of 27
      unmedicated middle aged normotensive men. The medicated group had a higher
      incidence of sexual dysfunction (56 pc) as compared to 11 pc in the control
      group. The use of hydrochlorothiazide did affect serum zinc levels significantly
      in 20 patients. Sexual dysfunction occurred more often in older and overweight
      patients (p < 0.004). Three of the normotensive men experienced sexual
      dysfunction probably related to old age. Twenty two of the 39 on
      hydrochlorothiazide and experiencing sexual dysfunction were divided into two
      groups of 11 patients. Bloods were taken from the 27 normotensive and 22
      hypertensive men receiving hydrochlorothiazide for the analyses of zinc.
      Subsequently one group of the patients were supplemented with zinc 500 mg daily
      for 30 days while the other group was supplemented with magnesium chloride 1 g
      daily for 30 days. The normotensive men were not treated. After 30 days, bloods
      were again taken from the three groups of analyses for zinc and magnesium. Serum
      zinc was significantly decreased (p < 0.05) by hydrochlorothiazide and a non
      significant decrease in serum magnesium (p = ns) was observed. After
      supplementation with zinc, the serum zinc levels returned to normal only in eight
      patients. There was improvement in the symptoms of sexual dysfunction in five
      patients. Two patients gained weight. Hydrochlorothiazide decreased serum zinc
      levels (p < 0.05) and was unchanged with magnesium supplementation but the serum
      magnesium returned to normal values. Improvement of symptoms of sexual
      dysfunction was positive in one patient. This study shows that low serum zinc
      levels may be associated with sexual dysfunction but the definitive role of zinc
      in the pathogenesis of sexual dysfunction will remain controversial.

PMID- 8556777
TI  - Neuropsychiatric HIV-1 infection study: in Kenya and Zaire cross-sectional phase
      I and II.
AB  - The objective of the study was to determine the prevalence and natural history of
      human immunodeficiency virus type 1 (HIV-1) associated psychiatric,
      neuropsychological and neurological abnormalities. A total of 408 subjects were
      recruited in Nairobi and Kinshasa. The study consisted of a cross sectional phase
      and a longitudinal follow up. Assessment was made by a data collection instrument
      including six modules. The intercentre and intracentre reliability in the use of
      the each module have been formally evaluated. The mean global score on the
      Montgomery-Asberg Depression Rating Scale was significantly higher in symptomatic
      seropositive individuals than in matched seronegative controls. In conclusion,
      these data suggest that the risk of subtle cognitive deficits may be increased in
      asymptomatic stages of HIV-1 infection.

PMID- 8556778
TI  - Malignant solid tumours in Nigerian children.
AB  - The subject of neoplasia in African children has received little or no attention
      within the past two decades. The current study retrospectively reviews malignant
      solid tumours in children from birth up to the age of 15 years over an 11 year
      period in Ile-Ife, Nigeria. During this period, 71 pc of solid tumours seen in
      children were malignant and boys were more often affected than girls. The peak
      incidence was between the ages of six and 13 years. Lymphoma was the commonest
      type of tumour, accounting for 72.6 pc of all malignant solid tumours and males
      predominated. All the rhabdomyosarcomas were seen in boys and the alveolar
      variant predominated. Osteogenic sarcoma and nephroblastoma were more often seen
      in girls. No primary brain tumour was seen.

PMID- 8556779
TI  - The diagnosis and management of gall bladder in private patients in Harare.
AB  - Gall bladder disease is getting more and more common in Africans. Some present
      with typical right upper quadrant pain but some are found on routine examination
      of the abdomen. The diagnosis is now very easy with ultrasound scan of the
      abdomen. The treatment used to be laparotomy and cholecystectomy but now is with
      laparoscopic surgery which leaves very little scarring. The results of the Harare
      study show chronic cholecystitis with cholesterol stones and very few
      bilirubinate stones.

PMID- 8556780
TI  - A case of dual chloroquine and halofantrine treatment failure in Zimbabwe.
AB  - A case of malaria treatment failure with chloroquine and halofantrine is
      reported. The likely determinants and policy considerations are addressed.

PMID- 8556781
TI  - Kaposi's sarcoma in a two week old infant born to a mother with Kaposi's
      sarcoma/AIDS.

PMID- 8556782
TI  - A simple decannulating method for suprapubic trocar and cannula without a side
      slit.
AB  - Closed suprapubic cystostomy using a suprapubic trocar and cannula is a standard
      surgical procedure for urinary diversion in cases of acute urinary retention.
      Decannulation is quite easy when the cannula has a side slit which allows easy
      detachment of the Foley catheter. However when the cannula is without a side slit
      decannulation becomes problematic. This simple decannulating method is described
      to overcome this difficulty.

PMID- 8556783
TI  - The effects of sickle cell disease on the families of affected children.

PMID- 8556784
TI  - Polio eradication initiative.

PMID- 8556785
TI  - The effect of various fluoride compounds on the development of experimental root
      surface caries in hamsters.
AB  - The aim of this investigation was to evaluate the effect of topical applications
      of various fluoride compounds on the development of root surface caries in
      hamsters. Male golden hamsters (n = 115) were divided into 7 groups and were
      given a caries-promoting diet. Six groups were infected with Actinomyces viscosus
      ATCC 15987; and to 5 infected groups, distilled water (DW) and solutions
      containing 500 ppmF of acidulated-phosphate fluoride (APF), stannous fluoride
      (SnF2), copper fluoride (CuF2), and titanium tetrafluoride (TiF4) were applied
      topically to the first mandibular molars once daily, 7 days a week, over a 24
      week period. A grid method was used to asses the periodontal changes and root
      surface caries on the first molars. Plaque accumulation was reduced most by SnF2;
      and alveolar bone loss was more reduced by SnF2 and CuF2. Root surface caries was
      significantly prevented in all fluoride groups when compared to an infected
      control group; and TiF4 was the most effective fluoride compound followed by
      SnF2, CuF2, and APF. Root caries scores of the TiF4 and SnF2 groups were
      significantly lower than those of the DW group. It was concluded that all
      fluoride tested may prevent the development of root surface caries in hamsters.

PMID- 8556786
TI  - Experimental root surface caries in hamsters the development of the disease after
      inoculations of two types of cariogenic bacteria.
AB  - The aim of this study was to investigate the development of root surface caries
      in hamsters fed a high-sucrose diet over a 24-week period after inoculations of
      two types of cariogenic bacteria. Twenty-one day old male golden hamsters (n =
      103) were divided into 5 groups. Four groups were given diet 2000, and one group
      was given a stock diet CE-2, Of the groups given diet 2000, three groups were
      infected with Actinomyces viscosus ATCC 15987 and Streptococcus mutans NTCC 10449
      separately (AV and SM groups) or in combination (AVSM group), and one group
      remained uninfected. A grid method was used to evaluate the plaque accumulation,
      alveolar bone loss, and root surface caries. After 12 weeks, root surface caries
      developed mainly on the first mandibular molars in the three infected groups. At
      24 weeks, the prevalence of root surface caries was highest in the AV group, but
      root caries scores were not significantly different among the three infected
      groups. In the groups SM and AVSM, the molar crowns were extensively destroyed by
      caries, while in the AV group the crowns were almost intact. It was concluded
      that challenge with Actinomyces viscosus may be appropriate to study root surface
      caries in hamsters.

PMID- 8556787
TI  - [Malaria situation in the People's Republic of China in 1994. Advisory Committee
      on Malaria, MOPH].
AB  - According to case reporting system, the number of malaria cases amounted to
      62,101 in the country (Taiwan Province not included) in 1994, showing a mean
      incidence of 5,292 per a hundred thousand, and 43 deaths were caused by the
      disease. An increase of 3,532 malaria cases was revealed while comparing with the
      data of 1993. A total of 1,083 billion population resided in areas where there
      were no reported malaria cases or the incidence was below 0.01%, 80 million in
      areas with incidence of 0.01-0.1%, and 10 million in areas with incidence of more
      than 0.1%. In Wanding City on located the border of Yunnan Province, the
      incidence remained over 1% in a population of 11,000. Malaria surveillance in
      major malarious areas located in 18 provinces/autonomous regions/municipalities
      (P/A/M) with a coverage of 0.53 billion population showed that 68,612 positive
      cases were detected from 11,068,110 febrile patients through blood examination,
      the mean positive rate being 0.62%. 3,928 malaria parasite carriers were
      discovered from 504,685 target and migratory population during general
      examination, the mean parasite carrier rate being 0.78%. In view of the fact that
      migratory immigrants were usually not included in the province-based case
      reporting system and case missing was likely to exist in the reporting process,
      the actual number of malaria cases was estimated to be no less than 100,000 in
      1994. More or less resurgence of malaria prevalence was noted in most of the
      southern P/A including Hainan, Yunnan. Guangxi, Guizhou and Fujian, while a
      decrease of incidence was reported in Guangdong and Sichuan. The situation of the
      former 5 P/A was attributed to the continuous expansion of migratory population,
      the existence of anopheline mosquitos with potent vectorial capacity, the
      inadequacy of funding allocation, and the difficulties in implementation of
      malaria control measures. Because of the increase in imported malaria cases from
      southern China, fluctuation of malaria prevalence was seen in 4 eastern P/M, i.e.
      Hunan, Jiangxi, Zhejiang and Shanghai. 7,959 falciparum malaria cases (comprising
      mixed infections of Plasmodium falciparum and P. vivax) were detected in the
      whole country in 1994, constituting 11.60% of the positive cases disclosed by
      blood examination; and 325 P. falciparum carriers were found in general
      examination. Hainan and Yunnan have been the principal endemic areas of
      falciparum malaria, whereas endogenous falciparum malaria cases were found in one
      county each in Guangxi and Guizhou. The occurrence of imported falciparum malaria
      cases was reported from 116 counties in 16 P/A/M (the above 4 P/A included).

PMID- 8556788
TI  - [Effect of environmental temperature, cryopreservation and aging on Plasmodium
      vivax sporozoites developing into exoerythrocytic stages].
AB  - After Anopheles stephensi mosquitoes with salivary infection of Plasmodium vivax
      were put in environments with temperatures of 30 +/- 1 degrees C, 26 +/- 1
      degrees C or 13 +/- 1 degrees C for 5 d, their glands were aseptically dissected
      and sporozoites were collected and inoculated into HepG2-A16 cell monolayers.
      Seven days post-inoculation the cultured materials were harvested and the
      exoerythrocytic schizonts and hypnozoites were observed under the microscope by
      using immunoperoxidase staining technique. The results showed that the sporozoite
      developing rate of 30 +/- 1 degrees C group and 13 +/- 1 degrees C group was
      significantly lower than that of 26 +/- 1 degrees C group (0.33%, 0.35% and 0.75%
      respectively). The proportion of hypnozoites in the total number of EE forms was
      the highest in the low temperature group (62.5%) compared with 26 +/- 1 degrees C
      and 30 +/- 1 degrees C group (40.1% and 42.7% respectively). Suggesting that the
      low environmental temperature first affected the viability of tachysporozoites or
      the phenotype of sporozoites and thus resulted in heightened hypnozoite rate.
      This is parallel to the epidemiological data that in the regions of high latitute
      vivax malaria with long incubation period was more frequently observed. When the
      sporozoites within the body of mosquito were cryopreserved at -70 degrees C or in
      liquid nitrogen for 24 h or 5 d respectively, the proportion of hypnozoite
      increased 87.4% and 82.4%, respectively. However, cryopreservation did not
      inactivate all of the tachysporozoites, indicating that the resistance to
      ultralow temperature in bradysporozoite was much greater than that in
      tachysporozoites. Aging of sporozoites decreased their developing rate and the
      exoerythrocytic (EE) schizonts were found to grow sluggishly and asynchronously,
      indicating that the size of EE schizont and the age of sporozoites are in
      negative correlation. Meantime, proportion of the hyponozoite decreased
      significantly.

PMID- 8556789
TI  - [Field studies on preventive effect of artemether against infection with
      Schistosoma japonicum].
AB  - From August to October 1994, a field trial of preventive treatment with
      artemether (Art) was carried out in Minglang District of Yiyang City, Hunan
      Province, an islet with embankment type endemic area nearby southern Donting Lake
      region. The residents who frequently contacted with the infested water were
      selected for study and allocated to the Art group and the control group in
      reference to paired methods of randomization table. About one month before
      administration of Art, all residents under study were examined by stool hatching
      technique after nylon-bag concentration to determine the infection rate of each
      group, and then treated with praziquantel at a single dose of 40 mg/kg in stool
      egg-negative residents and 50 mg/kg in stool egg-positive ones. In Art group, the
      first dose of 6 mg/kg was given in late August, followed by repeated dosing every
      15 days for 3 times. Placebo (starch) was given to the study residents in the
      control group at the same time as in Art group. The efficacy was evaluated by
      stool examination 25-32 days after the last medication. The results showed that
      after the preventive administration of Art, 20 out of 365 study residents in Art
      group revealed stool positive with an infection rate of 5.5%, while in the
      control group 51 out of 376 study residents showed stool positive with an
      infection rate of 13.6%. The difference between the two groups was statistically
      significant. Meantime, two cases of acute schistosomiasis were seen in the
      control group, but none was observed in Art group. The egg per gram of feces
      (EPG) determined with the Kato-Katz method was 122 +/- 79 (range 12-192) in Art
      group and 681 +/- 909 (range 12-2,760) in the control group. No apparent adverse
      side effect was seen during the treatment with Art, and no abnormal change in
      liver and renal function was detected after the last medication. The preliminary
      study indicates that application of the preventive administration of Art in the
      endemic area during the transmission season may effectively reduce both the
      infection rate and intensity of schistosomiasis.

PMID- 8556790
TI  - [Studies on diagnosis of falciparum malaria based on amplifying specific SSUrDNA
      fragment with nested PCR].
AB  - Two pairs of primers specific to small subunit ribosomal DNA of Plasmodium
      falciparum were designed and the expected SSUrDNA fragment was amplified for
      detecting P. falciparum infection with double-temperature-nested polymerase chain
      reaction using DNA prepared by boiling method. The results showed that the nested
      PCR could amplify a constant size of desired SSUrDNA fragment of P. falciparum
      which was further confirmed by digestion of restriction endonuclease and could
      detect parasitemia level of 0.8 x 10(-6). It has great potentials for identifying
      Plasmodium species in ring form of erythrocytic stage and detecting mixed
      Plasmodium infections. Therefore, it is suggested that this method is sensitive,
      accurate, simple and rapid in detecting Plasmodium falciparum in blood samples
      for malaria diagnosis.

PMID- 8556791
TI  - [Studies on the deltamethrin-medicated bath of domestic dogs for interrupting
      visceral leishmaniasis transmission].
AB  - In a previous paper, it was reported that deltamethrin-medicated bath of domestic
      dogs had a strong killing effect against Ph. chinensis, and could also inhibit
      its blood sucking ability or cause its death shortly after blood sucking. The
      effect could last for 30 days to 114 days, and mostly for 2 months in the local
      area. Based on our previous study, three villages (Yongle, Yongfeng, Anle) and a
      town (Chengguan) were selected from the mountainous region with high incidence of
      visceral leishmaniasis in Nanping County, northern Sichuan for carrying out an
      extensive experiment of medicated bathing of domestic dogs, where there were 13
      new infected cases in the year of 1991 before the experiment. During the sandfly
      season in 1992, two rounds of medicated bathing of dogs were conducted, the drug
      concentration used was 50 ppm. From September 1992 to August 1993, the number of
      new infected cases was 11 in the above mentioned three villages and a town.
      Another two rounds of medicated bathing of dogs had been conducted during the
      sandfly season in 1993. The results show that there was no new infection from
      September 1993 to October 1994 in the three villages and a town, indicating that
      through two years' consecutive extensive medicated bathing of dogs in the endemic
      areas, canine visceral leishmaniasis transmission had been significantly
      interrupted. The authors consider that in the mountainous region of southern
      Gansu and northern Sichuan where it has been difficult to treat dogs, it might be
      more practical to use deltamethrin bathing of dogs for interrupting the
      transmission of canine visceral leishmaniasis.

PMID- 8556792
TI  - [Studies on the enzyme cytochemistry of Toxoplasma gondii and the influence of
      artemether].
AB  - Male mice of Kunming strain were infected with 10,000 tachyzoites
      intraperitoneally. 2 hours after infection the mice were divided into 2 groups
      and administered 5% of amylum and 200 mg/kg of artemether by gavage for 8
      consecutive days. The ultrastructural enzyme cytochemical studies on cytidine
      monophosphatase (CMP-ase) and glucose-6-phosphatase (G-6-P-ase) of the parasites
      were carried out. CMP-ase was found scattered in the lysosomes of the parasites
      as well as in the macrophages. No differences were observed in the localization
      and intensity of CMP-ase activity between the nontreated and treated with drug
      parasites. G-6-P-ase was found surrounding the parasite membrane and scattered in
      the parasitophorous vacuole in the nontreated parasites. After treatment with
      artemether, the intensity of G-6-P-ase activity was decreased compared with
      nontreated control parasites. It is suggested that artemether may exert some
      action on the G-6-P-ase of T. gondii and thus influence the energy metabolis of
      the parasite.

PMID- 8556793
TI  - [Observation on hypnozoite of different isolates of Plasmodium vivax in cultured
      materials].
AB  - The hypnozoites of different isolates of P. vivax from Shenzhen and Shixin,
      Guangdong Province, Changsha, Hunan Province and Yincheng, Hubei Province of
      China in cultured materials were observed employing immunoperoxidase staining
      method. The percentages of hypnozoites among exoerythrocytic stages were 40.1,
      43.5, 50.6 and 57.1%, respectively, indicating that the percentage of hypnozoites
      and the latitude are in positive correlation. The equation is y = -6.68 + 2.05x.
      When the difference in latitude of Plasmodium vivax isolate source was more than
      5 degrees, a significant difference in the percentage of hypnozoites in various
      geographic isolates was found. However, the average diameters of hypnozoites and
      schizonts among various geographic isolates showed no significant difference. The
      results showed that in the regions north to the Yangtze River, the proportion of
      hypnozoite in the liver stage of P. vivax was larger than those in the southern
      China, being consistent with the clinical manifestations.

PMID- 8556794
TI  - [Effect of praziquantel treatment on serum circulating soluble egg antigen
      antibody complex (SEAIC) level in mice infected with Schistosoma japonicum].
AB  - Employing Capture ELISA, we determined the level of the circulating soluble egg
      antigen-antibody complex (SEAIC) in sera from mice infected with Schistosoma
      japonicum for 7 weeks and then treated the infected mice with praziquantel (100
      mg/kg body weight). It was noted that the serum SEAIC level in treated mice
      dropped gradually after treatment. There was a significant decrease in 13 out of
      15 mice in serum SEAIC levels at five weeks after treatment, OD value dropped
      from 0.358 +/- 0.074 to 0.165 +/- 0.049 (P < 0.01). The serum SEAIC level in 10
      mice declined to disappear (OD < 0.097) by the 7th week after treatment. By
      contrast, no significant changes in serum SEAIC levels were found in the non
      treated mice, the serum SEAIC level in the control group maintained moderately
      high (OD = 0.266 +/- 0.076) till the end of the observation.

PMID- 8556795
TI  - [Cost-benefit analysis on Malayan filariasis control in Miaoxi Township, Huzhou
      City, Zhejiang Province during 1964-1987].
AB  - The methods adopted in this paper were as follows: (1) The cost of the filariasis
      control was estimated to be direct cost and indirect cost; (2) Using the
      reduction rate of acute inflammatory attack as the measurable indicator of
      control effectiveness; (3) Estimating the case number of acute inflammatory
      attack occurred after control year by year basing on the goodness by fitting in
      the reduction trend of acute inflammatory attack with hyperbola formula; (4)
      Assuming that the case number of acute inflammatory attack would be relatively
      stable at the same level of pre-control if filariasis control measures were not
      implemented; (5) The benefit from the filariasis control was estimated by
      transforming the increasing man-working day and saving the medicine expenses of
      patients due to the reduction of acute inflammatory attack. By allowing seven
      percent discount on cost and benefit, the total cost was 21,182 Yuan, the total
      benefit was 119,859 Yuan, the ratio of cost-benefit was 1:5.7, implying that
      putting in one Yuan to filariasis control in this township may gain benefit 5.7
      Yuan.

PMID- 8556796
TI  - [Studies on mode of human infection with Echinochasmus liliputanus].
AB  - Epidemiological survey and experimental studies on the mode of human infection
      with Echinochasmus liliputanus were carried out in Chenqiaozhou Village, Hexian
      County, Anhui Province in 1992. The results showed that humans could be infected
      through drinking unboiled water containing E.liliputanus cercaria or eating raw
      fish containing the metacercaria. The infection rates of E. liliputanus were 1.5%
      in the inhabitants who did not drink raw water, and 20.1% in those who used to
      drink raw water. It was only the cercaria, not the metacercaria that was detected
      in the water from ponds of this village. None of the investigated inhabitants ate
      uncooked fish. The results indicated that drinking raw water containing
      E.liliputanus cercaria was a major way through which a humans were infected and
      eating food containing the metacercaria was a minor mode of human infection.

PMID- 8556797
TI  - [Acridine mutagen ICR-170 induced developmental suppression of ovary and
      vitelline gland in female Schistosoma japonicum].
AB  - Mice of Kunming strain were infected with Schistosoma japonicum cercariae
      previously incubated with various concentrations of acridine mutagen ICR-170 for
      different time durations. At 6 weeks after infection, the mice were autopsied.
      The results showed that 24 out of 28(85.7%) adult female worms had deformed or
      lacked ovaries and vitelline glands when the cercariae were treated with the
      agent at a concentration of 10 micrograms/ml and incubated at 30.5 degrees C for
      30min. No apparent changes were observed in the male worms inhabiting the
      mesenteric and portal veins with the females worms in their gynecophoral canals.
      The mutagenized female schistosomes obtained from the present experiment might be
      served as another form of attenuated worms for the induction of protective
      immunity.

PMID- 8556798
TI  - [Sequence analysis of apical membrane antigen I from a Plasmodium falciparum
      isolate collected from Mengpeng Township, Yunnan Province].
AB  - Genomic DNA from a Plasmodium falciparum isolate (CMP-1) collected from a
      falciparum malaria patient at Mengpeng Township, Mengla County, Yunnan Province
      was used as the template for PCR amplification primered with oligonucleotides
      from the conserved regions of the apical membrane antigen I (AMA-1) as reported.
      PCR products recovered from the low melting-point agarose gel electrophoresis
      were digested with BamHI and EcoRI to generate fragments approximately 420, 445
      and 900 bp which were used as the inserts to insert into the M13 mp8 and M13 mp9
      vectors for sequencing using 373 sequencer. 1773 bases were read out, among which
      17 point mutations were found to result in substitutions of 15 codens which were
      non-synonymous mutations except for one as compared with that of the consensus.
      In particular, a relatively hot region of variation was apparent between amino
      acids 160 and 210.

PMID- 8556799
TI  - [The inhibitory effects of immune sera against two recombinant hybrid antigens on
      the growth of Plasmodium falciparum in vitro].
AB  - The inhibitory effects of rabbit immune sera against two recombinant hybrid
      antigens (C and CAC) of Plasmodium falciparum to the multiplication and
      development of in vitro cultured P. falciparum parasites were tested. Although
      both of anti-C and anti-CAC immune sera had inhibitory effect on parasites, the
      anti-CAC serum showed much greater effect than that of anti-C serum (P < 0.05).
      The inhibitory capacities in the sera to parasites were enhanced with the
      increase in the serum concentration as well as with the prolongation of the
      incubation time of the sera with the parasites. It was shown that after 72 h
      incubation of the anti-CAC serum with the parasites at the concentration of 1%,
      10% and 20%, the inhibition rates were 15%, 54% and 82%, respectively. The immune
      sera caused the dispersion of parasite cytoplasm, atrophy of parasites,
      agglutination of free merozoites and degeneration of schizonts, suggesting that
      the hybrid antigen could produce multi-functional protective antibodies against
      antigens of Plasmodium falciparum.

PMID- 8556800
TI  - [Characteristics and recent trends in endemicity of human parasitic diseases in
      China].
AB  - An analysis of the nationwide survey of the distribution of human parasites in
      the light of the literature previously published, two major trends in the
      endemicity of parasitic diseases in China was observed. For one trend, the
      infection rate of E. histolytica, Fasciolopsis buski and soil-transmitted
      helminthasis etc. declined markedly. The second trend was that the prevalence of
      food-transmitted parasitic diseases (Trichinella spiralis, Clonorchis sinensis,
      Paragonimiasis, cysticercosis) and hydatidosis was increasing. The relationship
      between the social economic factors and the two trends were discussed.

PMID- 8556801
TI  - [Studies on elements in Anopheles sinensis infected with Brugia malayi
      microfilariae].
AB  - Amounts of Certain elements in Anopheles sinensis, both normal ones (emerged
      mosquitoes, d0, d5, d8, d12 and d18 after taking blood meal) and those infected
      with Brugia malayi microfilaria (d5, d8, d12 and d18 after infection), were
      determined using IL-551 and PE-603 atomic absorption spectrometer (AAS). The
      results showed that 9 kinds of trace elements including Fe, Zn, Cu, Cd, Al, Pb,
      Mn, Ni and Cr and 4 kinds of macro elements as K, Na, Ca, Mg were present in both
      the noninfected and infected mosquitoes. Comparing the contents of the elements
      between the noninfected and infected mosquitoes, the amounts of many kinds of
      elements reduced obviously in mosquitoes infected with microfilaria. The quantity
      and kinds of elements reduced in mosquitoes with the days of infection, for
      instance, 10 kinds of elements on the 5th day, 11 on the 8th day, 9 on the 12th
      day and 7 on the 18th day after infection (Tables 1, 2).

PMID- 8556802
TI  - [Observation on dynamics of circulating antigen from patients with cysticercosis
      before and after treatment].
AB  - The dynamics of circulating antigen (CAg) level in sera form patients with
      cysticercosis before and after albendazole treatment were detected by using
      monoclonal antibody-based double antibody sandwich ELISA (McAb-ELISA). The
      results indicate that after the patients with cysticercosis had been treated for
      one, two and three treatment courses, the levels of CAg in sera decreased with
      the increase in the number of treatment courses, their average OD value dropped
      from 0.499 before treatment to 0.291, 0.073 and 0.051 after treatment,
      respectively, and the corresponding negative conversion rates of CAg detection
      were 20.0%, 57.9% and 87.5%, respectively. Sera from eight patients who had
      received three courses of albendazole treatment were detected for CAg and CAb
      before and after treatment. The results indicate that the CAb level dropped
      rather slowly after three courses of treatment as compared to CAg level. It is
      concluded that detecting circulating antigen might be used as a promising method
      for evaluating the drug efficacy.

PMID- 8556803
TI  - [The course of malaria control and present status in Zhejiang Province].
AB  - Through forty years' sustained efforts in the prevention and treatment of malaria
      in Zhejiang Province, the malaria incidence dropped from 76.650/000 in the
      Fifties to 0.910/000 in the Eighties. Three malaria epidemics emerged in 1954,
      1962 and 1973, respectively, among them the epidemic in 1962 was the most serious
      one with 0.88 million cases reported and an incidence of 3300/000. The annual
      incidence of the overall counties/cities was below 10/000 after 1988. Only 172
      malaria cases were found in 1992, the incidence being 0.040/000. No indigenous
      malaria case was found in 38 counties in 1992, accounting to 43.7% of the total
      malaria endemic counties. The number of imported malara cases was 3,829,
      amounting to 89.2% of the total number of cases. Through the spot-check of the
      Ministry of Public Health in 1993, it was confirmed that the criteria of basic
      elimination of malaria in the province was attained.

PMID- 8556804
TI  - Are calcium antagonists safe?

PMID- 8556805
TI  - Methotrexate in rheumatoid arthritis: when NSAIDs fail.
AB  - Methotrexate has become the agent of choice for rheumatoid arthritis that does
      not respond to nonsteroidal anti-inflammatory drugs. In appropriately selected
      patients and with diligent monitoring, methotrexate in low weekly doses is
      effective and has a much better safety profile than was originally perceived.

PMID- 8556806
TI  - Acute dissection of the aorta: options for diagnostic imaging.
AB  - When dissection of the aorta is suspected, the physician needs to initiate
      medical therapy immediately, even before a final diagnosis is made. New imaging
      technologies are essential in making a diagnosis. In some cases, these new
      imaging modalities obviate the need for angiography.

PMID- 8556807
TI  - Deep venous thrombosis: low-molecular-weight heparins in perioperative
      prophylaxis.

PMID- 8556808
TI  - Postoperative confusion in a 42-year-old man.

PMID- 8556809
TI  - A 55-year-old man with chronic liver disease and coagulation abnormalities.

PMID- 8556811
TI  - The preoperative bleeding time test: assessing its clinical usefulness.
AB  - The bleeding time test can aid in the diagnostic evaluation of patients with
      clinical hemorrhagic disorders or a history of bleeding. However, its low
      positive predictive value in predicting perioperative bleeding should force one
      to abandon it as a routine preoperative screening test.

PMID- 8556810
TI  - Preoperative screening: what tests are necessary?
AB  - The preoperative evaluation often includes more tests than are necessary. This
      article reviews the usefulness of and indications for nine commonly ordered
      preoperative tests.

PMID- 8556812
TI  - Perioperative care of the elderly patient: special considerations.
AB  - Unlike older studies, which cited age as an independent risk factor for surgical
      mortality, recent studies indicate that the presence of underlying diseases and
      the type, duration and urgency of surgery are better predictors of outcome than
      age alone. A preoperative assessment that defines medical, functional, and
      psychosocial problems of elderly patients can lead to interventions to improve
      surgical outcomes.

PMID- 8556813
TI  - Evaluating cardiac risk in noncardiac surgery patients.
AB  - The cornerstones of the evaluation of cardiac risk in patients undergoing
      noncardiac surgery remain a thorough history and physical examination, and a
      resting electrocardiogram. However, new techniques to assess cardiac function
      allow more complete evaluation of high-risk patients.

PMID- 8556814
TI  - Postoperative pulmonary complications: risk assessment, prevention, and
      treatment.
AB  - Patients with pre-existing pulmonary disease and certain other conditions are at
      increased risk of postoperative pulmonary complications. This article surveys how
      internists can identify high-risk patients clinically, use pulmonary function
      studies, use specific therapy to reduce risk, and manage postoperative
      complications.

PMID- 8556815
TI  - Lack of association of apolipoprotein E polymorphism with plasma Lp(a) levels in
      the Chinese.
AB  - Apolipoprotein E (apoE) polymorphism and its influence on plasma lipids,
      lipoproteins, lipoprotein (a) [Lp(a)] and apolipoproteins was studied in 536 (270
      males and 266 females) healthy Chinese in Singapore. From analysis of variance
      with age and BMI as covariates, apoE genotype was found to exert a significant
      influence on plasma total cholesterol (TC), low-density lipoprotein cholesterol
      (LDL-C) and apoB in females. Its effect in males was marginally significant only
      on LDL-C. In both sexes, plasma TC, LDL-C and apoB were lower in those who were
      E2-3 than in those who were E3-3. There was no significant difference in log
      transformed Lp(a) level between the apoE genotypes after adjusting for the
      confounding effect of LDL-C in addition to age and BMI. The percentage variance
      (R2 x 100) of the lipid traits explained by apoE polymorphism in the females was
      4.94% for plasma TC, 5.85% for LDL-C and 4.25% for apoB. We conclude that: 1)
      epsilon 2 allele had a lowering effect on plasma TC, LDL-C and apoB; 2) apoE
      polymorphism did not have any significant influence on Lp(a) concentration; and
      3) the effect of apoE polymorphism on plasma TC, LDL-C and apoB was gender
      specific, with a stronger influence in females than in males.

PMID- 8556816
TI  - Retinitis pigmentosa in Spain. The Spanish Multicentric and Multidisciplinary
      Group for Research into Retinitis Pigmentosa.
AB  - Retinitis pigmentosa is a term commonly given to a group of inherited and
      progressive disorders which affect the photoreceptors of the retina. As part of
      an ongoing research programme throughout Spain, clinical, epidemiological, and
      genetic studies have been carried out on these diseases. Here, we report the
      relative frequencies of the different genetic types in 503 non-syndromic and 89
      syndromic RP families of Spanish origin. The most frequent syndromic RP forms
      were Usher syndrome type 1 (20/89 families = 30%) and Usher syndrome type 2 (44
      families = 49%). Among non-syndromic RP forms, 12% were autosomal dominant, 39%
      autosomal recessive and 4% X-linked. Forty-one percent were isolated or simplex
      cases and in 4% the genetic type could not be established.

PMID- 8556817
TI  - A rare G6490-->A substitution at the last nucleotide of exon 10 of the
      glucocerebrosidase gene in two unrelated Italian Gaucher patients.
AB  - Mutation screening of the glucocerebrosidase gene by SSCP analysis revealed an
      abnormal pattern of exon 10 in two unrelated Italian Gaucher patients. Direct
      sequencing of the mutated samples identified a G6490-->A transition. The same
      mutation has been described before in a Japanese patient with Gaucher disease
      type III. The clinical phenotype of our patients was type I in one whose second
      allele carried the N370S mutation and type II in the other one with a L444P
      mutation. In this latter the G6490-->A substitution cancels a normal Msp I site,
      while on the opposite chromosome the T6433-->C mutation (L444P) introduces a new
      Msp I site. Thus, digestion with Msp I of the amplified exon 10 is a useful
      method for identifying the two mutations simultaneously.

PMID- 8556818
TI  - A novel insertional mutation of a single base on exon 12 of the dystrophin gene.
AB  - A new point mutation in exon 12 of the dystrophin gene was identified in a DMD
      patient using multiple SSCP analysis, which allows the simultaneous study of
      several exons. The mutation is an A insertion at position 1580 of the cDNA
      sequence, leading to a stop codon in the translational reading frame. This
      mutation was not observed in a sample of 70 DMD patients.

PMID- 8556819
TI  - On the nosology of the "primary true microcephaly, chorioretinal dysplasia,
      lymphoedema" association.
AB  - We describe a male child with prenatal growth retardation, true microcephaly,
      pedal lymphoedema and characteristic ocular anomalies. Ophthalmological
      examination revealed remnants of the posterior hyaloidea, more pronounced in the
      right eye where a retinal fold extended from the papilla into the vitreum,
      chorioretinal dysplasia with narrow retinal vessels, multiple large round areas
      of chorioretinal atrophy and atrophic papillae. The associations "Microcephaly
      chorioretinal dysplasia", "Microcephaly-retinal folds" and "Microcephaly
      lymphoedema" have been reported as separate autosomal dominant conditions. The
      findings in the present child suggest that these associations could be variable
      expressions of the same autosomal dominant condition.

PMID- 8556820
TI  - Clinical phenotype associated with terminal 2q37 deletion.
AB  - Three children with deletions of the terminal portion of the long arm of
      chromosome 2 [del (2) (q37)] are described and their clinical findings compared
      to published cases of 2q terminal deletions. Common clinical findings include
      development delay, macrocephaly, frontal bossing, depressed nasal bridge and
      cardiac anomaly. Hypotonia and repetitive behavior are also seen during different
      times of development. The facial characteristics of children with 2q terminal
      deletions are not uniform, but development delay is a constant finding.
      Chromosomal analysis of such children using high resolution banding may uncover
      the diagnosis of a small chromosomal deletion.

PMID- 8556821
TI  - Monosomy 21q: two cases of del(21q) and review of the literature.
AB  - We report on two cases of partial monosomy 21 and review cases with a partial or
      an apparently full monosomy 21. In situ hybridization and/or molecular studies
      appear to be necessary tools to study imbalance in such a small chromosome and to
      perform further genotype-phenotype correlations. The segregation mode in cases
      with a translocation is adjacent 1, adjacent 2, and 3:1 in about 1/4, 1/4 and 1/2
      of the cases, respectively.

PMID- 8556822
TI  - Molecular cytogenetic studies of duplication 9q32-->q34.3 inserted into 9q13.
AB  - Fluorescence in situ hybridization (FISH) studies using whole chromosome 9
      painting probe, classical satellite (9q12-specific) probe and abl cosmid probe
      (locus: 9q34) were performed on a female infant who was born with multiple
      congenital anomalies and the karyotype 46,XX, 9q+. The results of FISH confirm
      the euchromatic nature of the extra material on the long arm of chromosome 9, and
      provide evidence that it is of chromosome 9 origin. The structural rearrangement
      has probably resulted from an insertion of a duplicated segment 9q32-->q34.3 into
      band q13, as shown by the abl cosmid probe. The clinical features in this patient
      are similar to the previously reported cases of partial trisomy 9q3.

PMID- 8556823
TI  - Cytogenetic and molecular cytogenetic studies of a case of interstitial deletion
      of proximal 15q.
AB  - A 4-month-old child with multiple anomalies was determined to have an
      interstitial deletion of chromosome 15, i.e., del(15) (q12q14). The deletion
      appears not to be a typical deletion of 15q12 such as seen in Angelman and Prader
      Willi syndromes, but appears to be more distal, involving either loss of all of
      15q12 and part of 15q14, or part of 15q12 and most of 15q14. In either case,
      15q13 is missing. Fluorescent in situ hybridization with probes for 15 centromere
      (D15Z), pericentromeric satellite sequences (D15Z1), and chromosome 15 painting
      probes shows the deleted chromosome to involve only 15 and no other acrocentric
      chromosome. Hybridization with probes for the AS and PWS loci (D15S11 and GABAB3,
      Oncor) show both sites to be intact in the deleted 15. The case is compared with
      two other reports with overlapping interstitial deletions of proximal 15q,
      neither of which shows typical features of Angelman or Prader-Willi syndromes.

PMID- 8556824
TI  - Joint dislocation and cerebral anomalies are consistently associated with oral
      facial-digital syndrome type IV.
AB  - We present a female patient with the oral-facial-digital syndrome type IV. Our
      report, the tenth in the literature, describes the typical manifestations of the
      syndrome, combined with malformations and deformations which have not always been
      described in the previously reported cases. They include cerebral and renal
      anomalies, anal atresia and dislocation of elbows and knees.

PMID- 8556825
TI  - Unexpected familial recurrence of iris coloboma. A delayed mutation mechanism?
AB  - Typical isolated ocular coloboma is a congenital abnormality caused by a
      defective closure of the embryonic fissure of the optic cup. Although an
      irregular autosomal dominant mechanism of inheritance has been proposed, there is
      some evidence of other modes of transmission and etiologies. This report shows an
      unexpected recurrence of iris coloboma, occurring in three sibships of the same
      family, that could be explained by a "delayed mutation" or "premutation"
      mechanism.

PMID- 8556826
TI  - A TaqI and a BamHI polymorphism in the COL4A4 gene on chromosome 2q35-37.

PMID- 8556828
TI  - Sister chromatid exchange in Prader-Willi syndrome families.

PMID- 8556827
TI  - A case of Alstrom syndrome associated with diabetes insipidus.

PMID- 8556829
TI  - Hepatitis C virus associated membranous glomerulonephritis.
AB  - Hepatitis C virus infection has been associated with a variety of extrahepatic
      disorders. We report four patients with membranous glomerulonephritis and
      hepatitis C virus infection. In contrast to patients previously reported with HCV
      infection and membranoproliferative glomerulonephritis, these patients have
      normal or minimally reduced complement levels and no evidence of rheumatoid
      factor or cryoglobulinemia. A liver biopsy in one patient was consistent with
      chronic active hepatitis although liver enzymes were only minimally elevated and
      coagulation studies normal. Three patients were treated with alpha-interferon
      with some success. Treatment with alpha-interferon may have a beneficial effect
      in reducing proteinuria and improving liver function and may be related to the
      ability of interferon to suppress viremia. Future studies need to focus on
      clarifying the role of the virus in causing glomerular disease and improving
      dosing strategies for alpha-interferon. Randomized, controlled studies need to be
      performed to determine whether the beneficial effect of alpha interferon is
      significant, and if so, if it is superior to conventional therapies.

PMID- 8556830
TI  - Monocyte chemoattractant protein-1 in normal and diseased human kidneys: an
      immunohistochemical analysis.
AB  - We conducted an immunohistochemical analysis to investigate the presence of
      monocyte chemoattractant protein-1 (MCP-1) in normal and diseased human kidneys
      and the correlation with infiltration of macrophages. A total of 50 renal
      biopsies were classified according to pathologic diagnosis. The distribution as
      well as the intensity of MCP-1 staining, and infiltration by CD68+ macrophages
      were evaluated in diseased versus normal kidneys. Weak staining of MCP-1 was
      detected in normal renal tissue, especially in tubular epithelial cells.
      Significant alterations in MCP-1 staining were observed in a number of diseases,
      in which the intensity of MCP-1 staining rather than the distribution of MCP-1
      positive cells was higher. In membranous nephropathy, IgA nephropathy, and
      glomerulosclerosis, an association was found between the intensity of MCP-1
      staining in tubular epithelial cells and interstitial infiltration of
      macrophages. The glomeruli in membranous nephropathy showed a stronger intensity
      of MCP-1 staining particularly in the glomerular visceral epithelial cells. The
      glomerular MCP-1 staining did not correlate significantly with the number of
      macrophages in the glomeruli. In conclusion, we describe increased cellular
      staining for MCP-1 in diseased human renal tissue, especially by tubular
      epithelial cells. Our observations suggest, complementary to in vitro and in vivo
      observations made by us and others, that specific roles may be played by MCP-1 in
      physiological and inflammatory processes in the kidney.

PMID- 8556831
TI  - Long-term ciclosporine A treatment in adults with minimal change nephrotic
      syndrome or focal segmental glomerulosclerosis.
AB  - To evaluate the efficacy and safety of long-term ciclosporine A (CSA) treatment
      in idiopathic nephrotic syndrome, we prospectively followed immunosuppressive
      therapy in 22 nephrotic adults for a median of 32 months (range 7-91 months) and
      obtained repeat renal biopsies. CSA induced complete remission in 60.0% and 14.3%
      of patients with minimal change nephrotic syndrome (MCNS) (n = 7), respectively.
      In addition, partial remissions were achieved in 20.0% of patients with MCNS and
      in 42.9% of patients with FSGS. Resolution of proteinuria was strictly CSA
      dependent and no sustained remission occurred following withdrawal, thereby
      requiring long-term treatment in 18 patients. In 10 patients CSA was administered
      for more than 43 months. During maintenance therapy the antiproteinuric effect of
      CSA was preserved and renal function as well as blood pressure remained stable in
      patients with MCNS, whereas renal function deteriorated in two patients with FSGS
      due to progression of the underlying renal disease. Renal biopsies revealed
      slight signs of CSA toxicity in four patients. However, in no case loss of renal
      function was attributable to these lesions. In conclusion, the present data
      suggest that long-term maintenance treatment of MCNS with CSA is efficacious and
      safe at least for a period of up to 43 months. In contrast, CSA has some effect
      on proteinuria in FSGS, but the results are less favorable.

PMID- 8556832
TI  - Isosorbide 5 mononitrate administration increases nitric oxide blood levels and
      reduces proteinuria in IgA glomerulonephritis patients with abnormal urinary
      endothelin/cyclic GMP ratio.
AB  - An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate
      increase in cGMP biosynthesis, was previously detected in some patients with IgA
      Nephropathy (IgAN). Since this imbalance might potentiate local ET1-mediated
      hemodynamics effects, 9 IgAN patients with an increased (> or = 0.1) urinary
      ET1/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and
      reduced ET1/cGMP ratio (group 2) were given standard doses of isosorbide 5
      mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as
      detected by electron paramagnetic resonance, significantly increased after
      isosorbide administration (p < 0.01) and decreased after drug discontinuation in
      both groups. Nitric oxide levels were significantly related with those of the
      effective renal plasma flow (p < 0.02), but not with the glomerular filtration
      rate. Proteinuria levels significantly decreased after drug administration (p <
      0.009) in group 1 and returned to baseline levels thereafter, except two cases
      showing persisting low levels. Values of filtration fraction in the same group
      decreased after iso5M administration (p < 0.02 compared to basal levels). These
      results may possibly be related to the counterbalancing effects of nitric oxide
      on endothelin-mediated mesangial contraction.

PMID- 8556833
TI  - Effects of chromium and guar on sugar-induced hypertension in rats.
AB  - Ingestion of sugars (sucrose, fructose, glucose) by various rat strains is
      associated with perturbations in the glucose/insulin system and higher systolic
      blood pressure (SBP). The association suggests causality, because alterations in
      insulin metabolism have been found in essential hypertension and many
      experimental forms of hypertension. To test the hypothesis that sugar-induced SBP
      elevation is secondary to perturbed insulin metabolism, we examined in 2
      experiments effects of chromium and guar, substances known to affect insulin
      metabolism, on SBP of Spontaneously Hypertensive Rats (SHR). In both studies,
      sucrose compared to starch ingestion caused significant elevation of SBP; but
      addition of 2 chromium nicotinate complexes and guar prevented development of
      sugar-induced SBP elevations. The basal, genetic hypertension of the SHR was not
      affected by either nutrient. An additional finding in the first study was that
      sugar-consuming SHR supplemented with chromium had greater BW and increased organ
      weight (kidney, spleen, and liver) than nonsupplemented SHR. Accordingly, we have
      shown that two different mechanisms known to ameliorate insulin perturbations,
      use of chromium and guar, prevent sugar-induced SBP elevations. Since essential
      hypertension may be due to insulin perturbations and high dose chromium
      supplementation seems nontoxic, this may prove to be a useful means to lower
      blood pressure (BP) in some essential hypertensives, as well as diabetic
      hypertensives. Soluble fiber in the form of guar is also quite effective in
      favorably influencing sugar-induced SBP elevations.

PMID- 8556834
TI  - Circulating type VI collagen and undulin, in patients with kidney diseases, after
      kidney transplantation and on hemodialysis.
AB  - Chronic kidney diseases are characterized by alterations in connective tissue
      turnover resulting in fibrosis. We measured circulating peptides related to type
      VI collagen and undulin in serum and urine of 125 patients with various kidney
      diseases, on chronic hemodialysis and after kidney transplantation. Using a
      double-armed ELISA technique (median, 95% CI), normal serum concentrations for
      type VI collagen were 50 ng/ml [46-63] with no type VI collagen detectable in
      urine. Normal values for undulin were 215 ng/ml [207-241] in serum and 240
      micrograms/d [223-284] in urine. The serum concentrations of undulin were most
      significantly (477 ng/mg [358-737]) increased in 18 hemodialysis patients. A
      significant increase (330 ng/ml [306-368]) was also observed in patients with
      various kidney diseases not requiring dialysis. No differences were found between
      the various forms of glomerulonephritis, interstitial nephritis and other kidney
      diagnoses. Although very low in normals (1.16 ml/min [1.05-1.27]) renal undulin
      clearance was even significantly lower in patients with kidney diseases (0.5
      ml/min [0.4-0.6]). Serum concentrations for undulin were in the normal range in
      the direct postoperative phase after kidney transplantation (207 ng/ml [167
      306]), whereas in kidney transplant out-patient levels were elevated to 425 ng/ml
      [357-563]. There was a slight but significant correlation between serum undulin
      and creatinine values and between renal undulin clearance and creatinine
      clearance. Values of serum type VI collagen increased in analogy to those of
      undulin. We conclude, that type VI collagen and undulin are novel serum
      parameters of renal extracellular matrix turnover that merit further exploration
      in patients with chronic kidney diseases.

PMID- 8556835
TI  - Role of calcium channel blockers in diabetic renal transplant patients:
      preliminary observations on protection from sepsis.
AB  - BACKGROUND: Diabetic recipients of kidney transplants have an excessively high
      risk of allograft loss, infectious complications with sepsis, cardiovascular
      events and early death. This study was designed in order to determine whether
      post-transplantation medical management influenced long-term results. METHODS:
      Seventy consecutive diabetic recipients of cadaveric renal allografts were
      followed from the time of transplant. Treatment regimens were based on the
      clinical judgement of transplant nephrologists and surgeons, not by the study
      team. Patients were followed for 2 to 9 years (mean follow-up of 50.85 months,
      one lost to follow-up). Groups were classified by HLA match, type of
      immunosuppression, prior cardiovascular history, type of antihypertensives (36 on
      calcium channel blockers, 32 on beta blockers, 8 ACE inhibitors). Events were
      defined as myocardial infarction, CVA, graft loss with return to dialysis, life
      threatening sepsis, or death. RESULTS: Twenty allografts failed during the study,
      24 patients died. Potentially cardioprotective drugs did not impact significantly
      on cardiac death, MI or CVA. Survivals were better when calcium channel blockers
      were used (mean 71.7 vs 38.6 months, p < 0.05; 4-year survival 84 vs 58%). When
      both beta and calcium channel blockers were used (n = 20), patients mean survival
      was 72.5 months vs 36.8 months for 21 patients who were not treated with blockers
      (p < 0.005). There was a lower incidence of graft loss when beta blockers and
      calcium channel blockers were used: at mean patient survival of 36.8 months, the
      no-blockers group had a mean graft survival of 19.3 months vs 72.5 months for
      blocker-treated patients (p < 0.002). Reinstitution of dialysis occurred less
      often with calcium channel blockers (17 vs 42%) or beta blockers (19 vs 38%) used
      either individually or together (5 vs 42%), all p < 0.05. Calcium channel blocker
      treated patients had 1/9 the number of septic deaths, fewer patients had multiple
      septic episodes, all p < 0.02. CONCLUSION: Allograft success and patient
      survivals may be improved and sepsis related events diminished when diabetic
      renal allograft recipients are treated with calcium channel blocking agents, plus
      or minus beta blockers. Considerable savings can be accomplished and graft
      results with these drugs can approach non-diabetic and live-related transplant
      results.

PMID- 8556836
TI  - Changes in diurnal blood pressure variation and red cell and plasma volumes in
      patients with renal failure who develop erythropoietin-induced hypertension.
AB  - Hypertension is the most common side-effect of treatment with recombinant human
      erythropoietin (EPO) for the anemia of chronic renal failure. To elucidate why
      this occurs in some patients we measured changes in blood volumes and diurnal
      blood pressure (BP) variation during treatment. Isotope labelled measurements of
      red cell and plasma volume (RCV and PV) were carried out along with ambulatory BP
      monitoring before starting EPO and after target hemoglobin (Hb) was reached. RCV
      did not differ between the patient group developing EPO-induced hypertension
      (EpHT, n = 11) and the group with no change in BP (NC, n = 13) either before or
      after treatment. However PV was significantly lower in the EpHT group after
      treatment (2.97 vs 3.92 litres; p < 0.025). Mean BPs differed little between
      groups because antihypertensive medications were increased as necessary for
      clinical safety but after achieving target Hb, day-night difference in diastolic
      BP was greater in the EpHT than the NC group (11.5 vs 4.6 mmHg; p < 0.025) due to
      a greater rise in daytime BP. There were significant correlations between high
      day-night diastolic BP differences after EPO in all the studied patients and low
      plasma volumes either pre- or post-EPO. The study group was heterogeneous but the
      changes were in the same direction irrespective of type of renal replacement
      therapy. These results suggest that EPO-induced hypertension is associated with
      increased daytime vasoconstriction and greater hemoconcentration due to lower
      plasma volume.

PMID- 8556837
TI  - The use of epoetin beta in anemic predialysis patients with chronic renal
      failure.
AB  - Two clinical studies were conducted to investigate the efficacy and safety of
      epoetin beta in 266 [corrected] anemic predialysis patients. Epoetin beta was
      administered subcutaneously either daily or thrice weekly. Mean duration of
      treatment was 211 days (interquartile range: 105 to 350 days). RESULTS: Renal
      anemia could be corrected and the regular transfusion need could be eliminated in
      all patients. There was no difference in the dose requirement per week between
      daily and thrice weekly administration of epoetin beta. Regarding the entire
      study population, there was no acceleration of the progression of renal failure
      during epoetin beta treatment nor were there any notable changes in laboratory
      values other than retention values. Epoetin beta was safe and well tolerated; the
      most important adverse event was the development or aggravation of hypertension.

PMID- 8556838
TI  - Mineralization defect but no effect on hypercalcemia during clodronate treatment
      in secondary hyperparathyroidism.
AB  - In four patients with severe secondary hyperparathyroidism, treatment with
      clodronate caused no decrease in serum calcium. In one of the patients treatment
      for seven months was associated with a severe mineralization defect which was not
      caused by aluminium. This lesion was reversible upon termination of clodronate
      treatment. In a single patient without hyperparathyroidism, a precipitous
      decrease in serum calcium was observed due to clodronate. However, long-term
      treatment with clodronate did not ameliorate ectopic calcification in this
      patient. It is concluded that in severe secondary hyperparathyroidism, clodronate
      does not always decrease serum calcium. Our experience suggest that clodronate
      like other bisphosphonates may inhibit bone mineralization.

PMID- 8556840
TI  - Prototype theory and compositionality.
AB  - Osherson and Smith (1981, Cognition, 11, 237-262) discuss a number of problems
      which arise for a prototype-based account of the meanings of simple and complex
      concepts. Assuming that concept combination in such a theory is to be analyzed in
      terms of fuzzy logic, they show that some complex concepts inevitably get
      assigned the wrong meanings. In the present paper we argue that many of the
      problems O&S discovered are due to difficulties that are intrinsic to fuzzy set
      theory, and that most of them disappear when fuzzy logic is replaced by
      supervaluation theory. However, even after this replacement one of O&S's central
      problems remains: the theory still predicts that the degree to which an object is
      an instance of, say, "stripped apple" must be less than or equal to both the
      degree to which it is an instance of "striped" and the degree to which it is an
      instance of "apple", but this constraint conflicts with and the degree to which
      it is an instance of "apple", but this constraint conflicts with O&S's
      experimental results. The second part of the paper explores ways of solving this
      and related problems. This leads us to suggest a number of distinctions and
      principles concerning how prototypicality and other mechanisms interact and which
      seem important for semantics generally. Prominent among these are (i) the
      distinction between on the one hand the logical and semantic properties of
      concepts and on the other the linguistic that between concepts for which the
      extension is determined by their prototype and concepts for which extension and
      prototypicality are independent.

PMID- 8556839
TI  - Other minds in the brain: a functional imaging study of "theory of mind" in story
      comprehension.
AB  - The ability of normal children and adults to attribute independent mental states
      to self and others in order to explain and predict behaviour ("theory of mind")
      has been a focus of much recent research. Autism is a biologically based disorder
      which appears to be characterised by a specific impairment in this "mentalising"
      process. The present paper reports a functional neuroimaging study with positron
      emission tomography in which we studied brain activity in normal volunteers while
      they performed story comprehension tasks necessitating the attribution of mental
      states. The resultant brain activity was compared with that measured in two
      control tasks: "physical" stories which did not require this mental attribution,
      and passages of unlinked sentences. Both story conditions, when compared to the
      unlinked sentences, showed significantly increased regional cerebral blood flow
      in the following regions: the temporal poles bilaterally, the left superior
      temporal gyrus and the posterior cingulate cortex. Comparison of the "theory of
      mind" stories with "physical" stores revealed a specific pattern of activation
      associated with mental state attribution: it was only this task which produced
      activation in the medial frontal gyrus on the left (Brodmann's area 8). This
      comparison also showed significant activation in the posterior cingulate cortex.
      These surprisingly clear-cut findings are discussed in relation to previous
      studies of brain activation during story comprehension. The localisation of brain
      regions involved in normal attribution of mental states and contextual problem
      solving is feasible and may have implication for the neural basis of autism.

PMID- 8556841
TI  - The two-stage model of lexical retrieval: evidence from a case of anomia with
      selective preservation of grammatical gender.
AB  - The two-stage theory of lexical production distinguishes the retrieval of lemmas
      from the subsequent retrieval of the forms of words. The information made
      available by lemma retrieval includes semantic and grammatical details that are
      specific to a particular word, but not the direct specification of its
      phonological or orthographic form. This theory makes very strong predictions
      regarding the dissociability of these information types. In this report, we
      present the case of an Italian anomic patient whose performance bears on these
      predictions. In various naming tasks this patient's intact ability to identify
      the grammatical gender of words that he cannot produce stands in stark contrast
      with his inability to provide any information regarding particular lexical forms.
      We document the reliability of this performance pattern, and we discuss the
      significance of this pattern both in terms of the support it provides for the two
      stage theory of lexical retrieval and in terms of the evidence it furnishes
      regarding the mental specification of grammatical information.

PMID- 8556842
TI  - Categorical effects in the perception of faces.
AB  - These studies suggest categorical perception effects may be much more general
      than has commonly been believed and can occur in apparently similar ways at
      dramatically different levels of processing. To test the nature of individual
      face representations, a linear continuum of "morphed" faces was generated between
      individual exemplars of familiar faces. In separate categorization,
      discrimination and "better-likeness" tasks, subjects viewed pairs of faces from
      these continua. Subjects discriminate most accurately when face-pairs straddle
      apparent category boundaries; thus individual faces are perceived categorically.
      A high correlation is found between the familiarity of a face-pair and the
      magnitude of the categorization effect. Categorical perception therefore is not
      limited to low-level perceptual continua, but can occur at higher levels and may
      be acquired through experience as well.

PMID- 8556843
TI  - The many faces of belief: reflections on Fodor's and the child's theory of mind.
AB  - I contrast Fodor's theory of the child's Very Simple Theory of Mind (VSTM), which
      differs from adult folk psychology only in that it recognizes fewer intentional
      objects, with my view that children's concepts cross-cut the adult conceptual
      system. More specifically, young children do not distinguish between the state of
      affairs a belief is about and how this state of affairs is though of, which puts
      a severe limit on their understanding of belief as distinct from pretence. The
      two different positions are evaluated against empirical data on children's
      developing "theory of mind".

PMID- 8556844
TI  - A representational analysis of numeration systems.
AB  - This article explores the representational structures of numeration systems and
      the cognitive factors of the representational effect in numerical tasks, focusing
      on external representations and their interactions with internal representations.
      Numeration systems are analyzed at four levels: dimensionally, dimensional
      representations, bases, and symbol representations. The representational
      properties at these levels affect the processes of numerical tasks in different
      ways and are responsible for different aspects of the representational effect.
      This hierarchical structure is also a cognitive taxonomy that can classify nearly
      all numeration systems that have been invented across the world. Multiplication
      is selected as an example to demonstrate that complex numerical tasks require the
      interwoven processing of information distributed across internal and external
      representations. Finally, a model of distributed numerical cognition is proposed
      and an answer to the question of why Arabic numerals are so special is provided.

PMID- 8556845
TI  - Realism and children's early grasp of mental representation: belief-based
      judgements in the state change task.
AB  - In a standard deceptive box procedure, children aged around 3 years typically
      fail to acknowledge their own prior false beliefs. For example, they judge
      incorrectly that they had initially thought a Smarties tube contained pencils
      after discovering these to be the actual content. Wimmer and Hart (1991) showed
      that children were more likely to answer correctly in a variant of this task
      known as a "state change", procedure. In this task, they saw that a container
      held its expected content (so the initial belief was true) before this was
      exchanged for something atypical. This appears to offer powerful evidence
      suggesting that children who fail the standard task do not understand about
      belief. However, we argue against this view. In a series of 4 experiments, we
      show that when children see the expected contents before these are swapped for
      something atypical, this not only makes it easier to report their own and a
      puppet's initial true belief but also a puppet's current false belief. The
      results are consistent with the "reality masking hypothesis", according to which
      facilitation is due to the belief option being linked with a physical counterpart
      in the state change procedure.

PMID- 8556846
TI  - German inflection: the exception that proves the rule.
AB  - Language is often explained as the product of generative rules and a memorized
      lexicon. For example, most English verbs take a regular past tense suffix (ask
      asked), which is applied to new verbs (faxed, wugged), suggesting the mental rule
      "add -ed to a Verb." Irregular verbs (break-broke, go-went) would be listed in
      memory. Alternatively, a pattern associator memory (such as a connectionist
      network) might record all past tense forms and generalize to new ones by
      similarity; irregular and regular patterns would differ only because of their
      different numbers of verbs. We present evidence that mental rules are
      indispensible. A rule concatenates a suffix to a symbol for verbs, so it does not
      require access to memorized verbs or their sound patterns, but applies as the
      "default," whenever memory access fails. We find 21 such circumstances for
      regular past tense formation, including novel, unusual-sounding, and rootless and
      headless derived words; in every case, people inflect them regularly (explaining
      quirks like flied out, sabre-tooths, walkmans). Contrary to the connectionist
      account, these effects are not due to regular words constituting a large majority
      of vocabulary. The German participle -t applies to a much smaller percentage of
      verbs than its English counterpart, and the German plural -s applies to a small
      minority of nouns. But the affixes behave in the language like their English
      counterparts, as defaults. We corroborate this effect in two experiments
      eliciting ratings of participle and plural forms of novel German words. Thus
      default suffixation is not due to numerous regular words reinforcing a pattern in
      associative memory. Because default cases do not occupy a cohesive similarity
      space, but do correspond to the range of a symbol, they are evidence for a memory
      independent, symbol-concatenating mental operation.

PMID- 8556847
TI  - Words as invitations to form categories: evidence from 12- to 13-month-old
      infants.
AB  - Recent research has documented specific linkages between language and conceptual
      organization in the developing child. However, most of the evidence for these
      linkages derives from children who have made significant linguistic and
      conceptual advances. We therefore focus on the emergence of one particular
      linkage--the noun-category linkage--in infants at the early stages of lexical
      acquisition. We propose that when infants embark upon the process of lexical
      acquisition, they are initially biased to interpret a word applied to an object
      as referring to that object and to other members of its kind. We further propose
      that this initial expectation will become increasingly specific over development,
      as infants begin to distinguish among the grammatical categories as they are
      marked in their native language and assign them more specific types of meaning.
      To test this hypothesis, we conducted three experiments using a modified novelty
      preference paradigm to reveal whether and how novel words influence object
      categorization in 12- to 13-month old infants. The data reveal that a linkage
      between words and object categories emerges early enough to serve as a guide in
      infants' efforts to map words to meanings. Both nouns and adjectives focused
      infants' attention on object categories, particularly at the superordinate level.
      Further, infants' progress in early word learning was associated with their
      appreciation of this linkage between words and object categories. These results
      are interpreted within a developmental and cross-linguistic account of the
      emergence of linkages between linguistic and conceptual organization.

PMID- 8556848
TI  - Spatial repetition blindness is modulated by selective attention to color or
      shape.
AB  - Subjects reported either the colors or shapes of two simultaneous masked letters.
      Our first study found that they were less accurate when the reported features
      were identical ("repetition blindness," or RB), while repetition along the
      unreported dimension had no effect. Three follow-up studies confirmed that when
      the same dimension was judged (overtly or covertly) for both stimuli, performance
      was only affected by repetition along that dimension. However, when different
      dimensions were judged for the two stimuli, performance was affected by
      repetition on both dimensions. These findings support new conclusions about both
      RB and visual attention. First, RB depends critically on visual attention, rather
      than simply on the stimulus presented or the overt response required. Second,
      while attention can be restricted to a single visual dimension, this is efficient
      only when the same dimension is selected for both objects. Selecting the color of
      one object and the shape of another simultaneous object results in both
      dimensions being accessed for both objects.

PMID- 8556849
TI  - Reforming Georgia's mental health system.
AB  - Legislation passed in 1993 makes sweeping administrative structural changes in
      Georgia's mental health system. Underlying these changes is the core value that
      consumers and families should be empowered to participate in the design,
      contracting, and evaluation of services. The key structural component is the
      creation of regional boards, comprised of at least 50% consumers and family
      members, which have the capacity to plan and contract for services and to
      evaluate the outcomes of those services. This paper describes Georgia's mental
      health system before these changes, the development of the initiative for reform,
      the process and problems associated with the passage of the legislation, and the
      current status of the implementation of the legislation.

PMID- 8556850
TI  - The California Adult Performance Outcome Survey: preliminary evidence on
      reliability and validity.
AB  - Recent legislation in California mandated the development of an outcome measure
      suitable for measuring changes in quality of life associated with treatment in
      the public mental health system. The measure, known as the California Adult
      Performance Outcome Survey (CAPOS), relies on clinician and client reports of
      objective and subjective indicators of quality of life. The present study sought
      to determine whether the clinician-administered CAPOS would agree with that
      administered by trained research assistants, and whether the CAPOS would agree
      with an established quality of life measure. A sample of sixty-four severely
      mentally ill subjects were assessed by their regular mental health provider using
      the CAPOS. One week later they were assessed by a trained research assistant
      using the CAPOS and Lehman's Quality of Life Interview (QOLI). For most outcome
      domains, the CAPOS exhibited moderate to excellent agreement across occasions and
      raters. Correlations with the QOLI indicated a good degree of overlap among
      corresponding domains. Outcome measurement procedures for routine use in clinical
      settings are in their infancy. The CAPOS appears promising in this role because
      of its brevity, ease of administration, and adequate interrater reliability. The
      CAPOS affords state and local mental health authorities with an efficient means
      of tracking key quality of life indicators within the public mental health
      system.

PMID- 8556851
TI  - Brief child assessment battery to assist with treatment planning and program
      evaluation.
AB  - A brief battery of self-report measures was constructed to discriminate
      effectively 45 matched clinic versus nonclinic subjects, ages 8 to 15. The
      battery consisted of measures from six domains, including externalizing problems,
      child and parent report of internalizing problems, peer relations, school
      functioning, and family relationships. Data on subjects and their families were
      provided by various sources, including parents, teachers, and the children. In an
      effort to facilitate interpretation and use of this information by
      unsophisticated staff, within domain scores were converted to bivariate risk
      scores. Results indicated effective classification (82%) of groups using the
      bivariate risk scores alone. This constituted only a small loss of information
      when the risk scores replaced t-scores. Implications for the use of the risk
      scores to facilitate treatment planning and program evaluation are discussed.

PMID- 8556852
TI  - Ideologies of care in community residential services: what do caregivers believe?
AB  - Ideologies of care, or systems of beliefs about the importance of particular
      goals and activities, help guide how care is provided. One currently pervasive
      ideology of care is that of normalization. In this paper, the ideologies of care
      of both house managers and direct care staff in group homes are contrasted.
      Results indicate that the ideology of direct care staff is less differentiated
      than that of the house managers. In addition, house managers are more likely to
      subscribe to a normalization ideology and less likely to subscribe to a family
      orientation ideology than are direct care staff. Ideological differences between
      house managers and direct care staff are only partially explained by differences
      in the demographic composition of the two groups.

PMID- 8556853
TI  - Emergency care avoidance: ethnic matching and participation in minority-serving
      programs.
AB  - Using data from a county level mental health service system, relationships were
      examined between ethnic matching, program involvement and emergency service use.
      When clients were matched with an ethnically similar clinician who was also
      proficient in their preferred language, they had fewer emergency service visits
      than did clients who were unmatched on the basis of ethnicity and language.
      Equally if not more significant than ethnicity or language matching was the
      client's program and the proportion of minority clients it served. Clients in
      programs serving a relatively large proportion of minority clients had fewer
      emergency service visits than those in programs serving a smaller proportion of
      minority clients. More research is needed to document the impact of matching
      along with greater attention to minority oriented programs.

PMID- 8556855
TI  - Society of Critical Care Medicine 25th Educational and Scientific Symposium. New
      Orleans, Louisiana, February 5-9, 1996. Abstracts.

PMID- 8556854
TI  - The economic advancement of the mentally ill in the community: 2. Economic
      choices and disincentives.
AB  - In order to evaluate the extent to which economic factors influence the life
      choices of people with mental illness, we interviewed 50 mentally ill people
      living in Boulder, Colorado. Subjects experience significant financial
      disincentives to work. The average total cash and noncash income of part-time
      employed subjects ($1,028 a month) is only modestly higher than that of
      unemployed subjects ($929 a month). Most clients calculate that $5 is the minimum
      hourly wage which makes work economically practical. Work disincentives could be
      improved by a more appropriately graduated scheme for reducing disability
      benefits for beginning workers. A wage subsidy would provide a work incentive to
      underproductive clients. Psychiatric treatment costs for unemployed subjects in
      this sample are twice those for the part-time employed. We suggest that research
      is needed to determine if treatment costs can be reduced by paying clients a wage
      subsidy.

PMID- 8556856
TI  - The influence of polyvinylpyrrolidone on freezing of bovine IVF blastocysts
      following biopsy.
AB  - A study was conducted to develop a better freezing protocol for in vitro
      developed biopsied bovine blastocysts. Biopsied blastocysts were exposed to 1.8 M
      ethylene glycol (EG) + 0.05 M trehalose (T) and different concentration (5, 10,
      and 20%) of polyvinylpyrrolidone (PVP). Exposure to the solutions alone did not
      affect their in vitro development (Experiment 1). Experiments 2, 3, and 4 tested
      the viability of biopsied blastocysts cryopreserved in 1.8 M EG + different
      concentrations of T (0, 0.05, 0.1, and 0.3 M), 1.8 M EG + different
      concentrations of PVP (0, 5, 10, and 20%), and 1.8 M EG + 0.05 M T + different
      concentrations of PVP (0, 5, 10, and 20%), respectively. The proportion of
      biopsied blastocysts that reexpanded following cryopreservation in 1.8 M EG +
      0.05 M T (38.5%) and 1.8 M EG + 0.1 M T (36.1%) was significantly (P < 0.05)
      higher than the proportion that reexpanded in 1.8 M EG + 0.3 M T (13.9%)
      (Experiment 2). The viability and the percentage of embryos that developed to >
      250 microns in diameter in the 5, 10, and 20% PVP groups (77.8 and 50.0%, 78.1
      and 43.8%, 76.9 and 65.4%, respectively) were significantly higher than those
      that developed cryopreserved without PVP (55.1 and 20.7%) (Experiment 3). Optimum
      development of in vitro culture of frozen-thawed biopsied blastocysts was
      obtained using 1.8 M EG + 0.05 M T and 20% PVP. Analysis of blastocysts > 250
      microns in diameter showed that the number of ICM cells of biopsied blastocysts
      cryopreserved in 1.8 M EG + 0.05 M T with or without PVP was not different from
      the number of unfrozen biopsied blastocysts. These results indicate that PVP has
      some beneficial effect on freezing of biopsied bovine blastocysts.

PMID- 8556857
TI  - Definition of optimal conditions for collection and cryopreservation of umbilical
      cord hematopoietic cells.
AB  - Prior studies have shown that human umbilical cord blood cells can restore
      hematopoiesis and be used as a source of stem cells for hematopoietic
      transplantation. We have performed a study of the best conditions of collection
      and cryopreservation of blood from eight umbilical cords. We compared the
      influence of cell separation and of delay between collection and cryopreservation
      on the numbers of nucleated cells and of hematopoietic progenitors recovered
      before and after cryopreservation. Ficoll separation resulted in the loss of more
      than 50% of nucleated cells, but also of a significant number of progenitors
      before freezing. Unseparated cells could be kept at 25 degrees C as long as 24 h
      before freezing with minimal loss of progenitors before and after freezing and
      thawing. In contrast, there was a significant decrease in the number of viable
      cells and progenitors when cells were maintained at 4 degrees C before freezing.
      Our data show that cord blood banking is feasible with simple collection and
      cryopreservation procedures.

PMID- 8556858
TI  - Antifreeze protein does not confer cold tolerance to transgenic Drosophila
      melanogaster.
AB  - Fish antifreeze proteins (AFPs) have been reported by some researchers to prolong
      the viability of tissues, organs, and embryos under hypothermic conditions, while
      others have observed no such effect or even AFP-mediated cryotoxicity. We
      examined the influence of Type III AFP from Atlantic wolffish on cold tolerance
      in a whole animal model system, transgenic Drosophila. The activity of the AFP,
      transgenically expressed under the transcriptional control of the female-specific
      yp1 and yp2 promoters and secreted into fly hemolymph, was confirmed through
      thermal hysteresis and differential scanning calorimetry measurements as well as
      through observations of ice crystal morphology. In cold exposure trials, at 0
      degrees C and at -7 degrees C, transgenic adult flies of both sexes exhibited
      greater survival than nontransgenic controls even though the antifreeze was only
      produced in females. We attribute these observations to the expression of the
      xanthine dehydrogenase marker gene used to identify transgenics, rather than the
      production of AFP. Type III AFP therefore appears unable to enhance survival of
      adult Drosophila under hypothermic conditions.

PMID- 8556859
TI  - Effects of cryopreservation on immune responses. VIII. Enhanced secretion of
      interferon-gamma by frozen human peripheral blood mononuclear cells.
AB  - The effect of freezing on phytohemagglutinin-induced interferon-gamma (IFN-gamma)
      production by human peripheral blood mononuclear cells (PBMCs) was studied. The
      possible mechanisms responsible for the observed effects were also analyzed.
      Frozen PBMCs produced significantly larger quantities of IFN-gamma than fresh
      cells. Like the frozen cells, the monocyte- and natural killer cell-eliminated
      populations of fresh PBMCs also secreted significantly larger quantities of IFN
      gamma. In contrast, the freezing process had no enhancing effect on IFN-gamma
      production by monocyte-depleted PBMCs. Irradiated PBMCs also secreted larger
      quantities of IFN-gamma. The results suggest that functional inactivation of a
      subset of cryosensitive suppressor monocytes is associated with an increase in
      IFN-gamma production by the T lymphocytes. The results provide further evidence
      that monocytes mediate their suppressive effect through the activation of a
      subset of radiosensitive, immuno-down-regulatory T cells. The ability of frozen
      cells to produce larger quantities of IFN-gamma should be of clinical importance.
      For instance, cancer patients receiving frozen PBMCs as stem cell support (after
      myeloablative radio/chemotherapy) should benefit from the increased IFN-gamma
      secretion because of its potent immunoregulatory, microbicidal, and antitumor
      activities.

PMID- 8556860
TI  - Re: An inexpensive method for freezing human peripheral blood mononuclear cells
      (PBMCs)

PMID- 8556861
TI  - MRI of the shoulder.
AB  - Magnetic resonance imaging of the shoulder is routinely used, especially in the
      evaluation of rotator cuff disease and glenohumeral instability. More recent
      studies have provided a more sophisticated understanding of what represents a
      pathologic rotator cuff. Similarly, there has been an increased focus on the role
      of the glenohumeral ligaments and their labral attachment sites in maintaining
      glenohumeral stability. There have been technical advances as well, including the
      increased use of magnetic resonance arthrography. In addition, newer studies have
      shed light on the pathophysiology of the long bicipital tendon and compression
      neuropathies involving the suprascapular and axillary nerves.

PMID- 8556862
TI  - Bacterial insertion sequences.

PMID- 8556863
TI  - P elements in Drosophila.

PMID- 8556864
TI  - The Tc1/mariner transposon family.

PMID- 8556865
TI  - The En/Spm transposable element of maize.

PMID- 8556866
TI  - The maize transposable element activator (Ac).

PMID- 8556867
TI  - The Mutator transposable element system of maize.

PMID- 8556868
TI  - Transposon Tn7.

PMID- 8556869
TI  - Tn10 and IS10 transposition and chromosome rearrangements: mechanism and
      regulation in vivo and in vitro.

PMID- 8556870
TI  - Transposition of phage Mu DNA.

PMID- 8556871
TI  - Videofluoroscopic evaluation of patients with Guillain-Barre syndrome.
AB  - We reviewed 14 patients with clinically confirmed Guillain-Barre syndrome for
      swallowing dysfunction. All had swallowing dysfunction varying from mild to
      severe. Six patients (43%) had equivalent impairment during oral and pharyngeal
      phases. Seven patients (50%) had more severe functional abnormalities during the
      pharyngeal phase than during the oral phase. One patient (7%) had moderate
      disorder during the oral phase and mild disorder during the pharyngeal phase.
      Thirty-six percent of the patients had moderate-to-severe dysfunction during the
      oral phase, and 71% had moderate-to-severe dysfunction during the pharyngeal
      phase. In 5 patients who had multiple sequential examinations, moderate or severe
      swallowing disorders improved to mild-to-moderate disorders within 4-8 weeks
      after the onset of the symptoms. Residual swallowing disorders may be seen in
      those who had severe swallowing dysfunction during the later phases of their
      disease. Further investigations are needed to determine if swallowing
      abnormalities persist after complete recovery from Guillain-Barre syndrome.

PMID- 8556872
TI  - Prepharyngeal dysphagia in Parkinson's disease.
AB  - Dysphagia in patients with Parkinson's disease (PD) is most often attributed to
      pharyngeoesophageal motor abnormalities. In our study of patients with idiopathic
      PD, attention was focused on prepharyngeal symptoms and motor functions. Using
      the Hoehn and Yahr disease severity scale, patients were grouped into those with
      mild/moderate disease [subgroup I (n = 38)] and those with advanced disease
      [subgroup II (n = 34)]. Dysphagia symptoms were present in 82% of all patients,
      but subgroup I patients voiced significantly more complaints. Conversely, many
      prepharyngeal abnormalities of ingestion, including jaw rigidity, impaired head
      and neck posture during meals, upper extremity dysmotility, impulsive feeding
      behavior, impaired amount regulation, and lingual transfer movements were
      statistically more frequent in subgroup II patients. Impaired mastication and
      oral preparatory lingual movements were the most common aberrations observed
      during dynamic videofluoroscopy (48/71), with most patients being concordant for
      both. The motor disturbances of ingestion reported herein reflect the
      disintegration of volitional and automatic movements caused by PD-related
      akinesia, bradykinesia, and rigidity.

PMID- 8556874
TI  - What is dysphagia?

PMID- 8556873
TI  - Influence of cold stimulation on the normal pharyngeal swallow response.
AB  - We examined the potential influence of cold stimulation of the anterior tonsillar
      pillars, before and after topical anesthesia, on the temporal linkage between the
      oral and pharyngeal components of the swallow. We hypothesized that if
      elicitation of the pharyngeal swallow were dependent upon stimulation of faucial
      mucosal receptors this response would be facilitated by cold tactile stimulation
      and inhibited by topical anesthesia. In 14 healthy volunteers undergoing
      simultaneous videoradiography and manometry we measured and compared regional
      transit and clearance times, and the timing of hyoid motion, upper esophageal
      sphincter relaxation, and opening within the swallow sequence. There was a
      significant, volume-dependent forward shift in timings of hyoid motion, upper
      esophageal sphincter (UES) relaxation profile, and opening which were influenced
      neither by cold stimulation nor topical anesthesia. Regional transit and
      clearance times and UES coordination were not influenced by cold stimulation.
      Pharyngeal clearance time was prolonged by tonsillar pillar anesthesia due to
      earlier arrival of the bolus head at this region (p = 0.002). We conclude that
      the normal pharyngeal swallow response is neither facilitated nor inhibited by
      prior cold tactile stimulation or topical anesthesia to the tonsillar pillars,
      respectively. These observations do not support the hypothesis that elicitation
      of the pharyngeal swallow response is dependent upon stimulation of mucosal
      receptors in the tonsillar arches.

PMID- 8556875
TI  - Limb girdle muscular dystrophy: a radiologic and manometric study of the pharynx
      and esophagus.
AB  - Limb girdle muscular dystrophy (LGMD) is not a recognized cause of dysphagia.
      However, a systematic study of pharyngoesophageal function in LGMD has not been
      performed or reported. We determined whether the dystrophic process involves the
      pharyngoesophageal musculature in 20 LGMD patients with and without complaints of
      deglutition. Pharyngeal and esophageal function was evaluated by conventional
      cineradiography and manometry. Abnormalities were demonstrated in 30% (6/20) of
      patients: dysphagia in 10% (2/20), an abnormal radiologic study in 30% (6/20),
      and an abnormal manometric study in 20% (4/20). Mean manometric pressures were
      not significantly different when patients were compared with a healthy, age- and
      sex-matched volunteer group. In 2 patients, dysfunction of the pharyngeal
      striated muscle was likely, or possibly, due to dystrophic affection of the upper
      alimentary tract. Significant upper alimentary tract dysfunction in LGMD is not
      common. The cause-effect relationship between the dystrophic process and the
      nonspecific pharyngoesophageal motility disorders is unclear and requires
      pathologic study.

PMID- 8556876
TI  - Esophageal dysfunction due to neurological disorders.

PMID- 8556877
TI  - A prospective psychological evaluation of patients with dysphagia of various
      etiologies.
AB  - We hypothesized that patients who complain of dysphagia without demonstrable
      organic abnormality may have an underlying psychological dysfunction. We thus
      conducted a comprehensive assessment in three groups of patients with dysphagia.
      Dysphagia was classified as obstructive (Obst) when an obstructive lesion was
      present on esophagoscopy or barium swallow, motility-related (Mot) when abnormal
      motility was shown on esophageal manometry in the presence of normal
      esophagoscopy or barium swallow, or nonobstructive, nonmotility-related (NONM)
      when manometry and esophagoscopy or barium swallow were both normal. We
      prospectively evaluated 71 patients with Obst-dysphagia, 15 patients with Mot
      dysphagia and 10 patients with NONM-dysphagia with a battery of standardized
      psychological tests including the Minnesota Multiphasic Personality Inventory
      (MMPI), the Symptom Checklist-90-Revised (SCL-90-R), and the Millon Behavioral
      Health Inventory (MBHI). The results indicate that patients with NONM-dysphagia
      have psychological attributes similar to those found in patients with Obst
      dysphagia or Mot-dysphagia. Combination of scores for parameters such as
      somatization, depression, and anxiety could not distinguish among the three
      groups of dysphagia patients. We thus conclude that patients with NONM-dysphagia,
      as a group, have similar psychological profiles compared to patients with
      dysphagia due to organic causes.

PMID- 8556878
TI  - Normal adult swallowing of liquid and viscous material: scintigraphic data on
      bolus transit and oropharyngeal residues.
AB  - Scintigraphic data are provided for 20 normal control subjects, 39-65 years of
      age. Each subject swallowed 10 cc of water and 10 cc of a more viscous material
      (1,100 centipoise) consisting of apple juice thickened with Thick-It, a
      commercial food thickener. The test substances were combined with 2.5 mCi Tc-99m
      sulfur colloid. Scintigraphic data were acquired in dynamic mode for 10 sec at 25
      frames/sec as the subject swallowed. Time-activity (TA) data were used to compute
      transit times, percentage residues in the mouth and pharynx, percent ingested,
      and a derived swallow efficiency score. The liquid was ingested in a single
      swallow by all subjects, and 9 cc was actually transferred to the esophagus. In
      contrast, for the viscous material, 11/20 subjects performed a second clearing
      swallow within the 10-sec interval. On the first swallow with the viscous
      substance, an average of 7 cc was transferred to the esophagus. Scintigraphy
      offers an excellent technique for determining natural and preferred volumes for
      swallowing a variety of bolus consistencies, since it can quantify the volume of
      each swallow or partial swallow. In this group of subjects the oral discharge
      time was shorter with the viscous material than with the water, but the
      pharyngeal transit times were not significantly different for the two bolus
      consistencies. Numerical efficiency scores were lower for the viscous material,
      indicating that such a measure is bolus dependent.

PMID- 8556879
TI  - Effect of oral sensorimotor treatment on measures of growth and efficiency of
      eating in the moderately eating-impaired child with cerebral palsy.
AB  - Thirty-five children with cerebral palsy and moderate eating impairment were
      studied to determine the effect of oral sensorimotor treatment (OST) on eating
      efficiency and measures of growth (weight gain). After taking effects of
      maturation into account, 11 children who received OST (group A) exceeded their
      expected centile line by 1.7 percentile points after 10 weeks of treatment.
      Chewing exercises alone (group B) had no effect on weight gain. Although small
      decreases occurred in the time needed to eat three standard textures of food
      (solid, viscous, puree) in groups A and B, these were not significant. Children
      maintained their weight-for-age percentile line although at the lower end of
      expected norms. These children will be at risk of growth failure because of the
      increased energy demands once they enter their teenage growth spurt. The clinical
      implications of these findings are that prolonged mealtime and oral-motor
      therapies may be adequate through the childhood years. Thereafter, children's
      growth must be monitored carefully, and oral caloric supplementation is suggested
      to provide the necessary energy for growth.

PMID- 8556880
TI  - Oral-motor skills following sensorimotor therapy in two groups of moderately
      dysphagic children with cerebral palsy: aspiration vs nonaspiration.
AB  - The purpose of this study was to determine the effect of oral sensorimotor
      treatment on oral-motor skills and measures of growth in moderately eating
      impaired children with cerebral palsy who were stratified by state of
      aspiration/nonaspiration. Twenty-seven children aged 2.5-10.0 years participated
      in this study (aspiration: n = 7, nonaspiration: n = 20). Weight and skinfold
      measures were taken. Children were observed at lunch time and six domains of
      feeding were examined: spoon feeding, biting, chewing, cup drinking, straw
      drinking, swallowing, and drooling. Children underwent 10 weeks of control and 10
      weeks of sensorimotor treatment, 5-7 minutes/day, 5 days/week. Treatment
      compliance for the entire group was 67%. Children who aspirated had significantly
      poorer oral-motor skills in spoon feeding, biting, chewing, and swallowing than
      children who did not aspirate. There was significant improvement in eating: spoon
      feeding (fewer abnormal behaviors, p < 0.03), chewing (more normal behaviors, p <
      0.003), and swallowing (more normal behaviors, p < 0.008). There were no
      significant changes in drinking skills. Children as a group maintained their
      pretreatment weight-age percentile but did not show any catch-up growth. Children
      showed adequate energy reserves as measured by skinfold thicknesses. Improvement
      in oral-motor skills may help these children to ingest food more competently
      (i.e., less spillage). However, their weight remains at the lowest level of age
      norms.

PMID- 8556881
TI  - Acute thermal injury of the esophagus.
AB  - Acute thermal injury to the esophagus has not been reported previously in the
      radiographic literature. We present a case of a young adult who developed an
      intramural "blister" that ultimately communicated with the esophageal lumen. A
      double-contrast esophagogram outlined the resulting mucosal flap. A brief review
      of other injuries to the esophagus is included.

PMID- 8556882
TI  - Late dysphagia after presternal colon interposition.
AB  - Esophageal replacement by colon interposition is done for a variety of esophageal
      diseases. Dysphagia occasionally develops many years after successful colon
      interposition. Redundancy of the colon graft is usually responsible. We report a
      patient with onset of dysphagia 24 years after presternal colon interposition for
      long segment esophageal atresia. Pathophysiology, prevention, and treatment of
      late colon interposition dysfunction are discussed.

PMID- 8556883
TI  - Reconsidering the value of the modified Evan's blue dye test: a comment on
      Thompson-Henry and Braddock (1995)

PMID- 8556884
TI  - Comment on Thompson-Henry and Braddock: the modified Evan's blue dye procedure
      fails to detect aspiration in the tracheostomized patient: five case reports.

PMID- 8556885
TI  - Preswallow sensory input: its potential importance to dysphagic patients and
      normal individuals.

PMID- 8556886
TI  - Parents' attributions for their children's behavior.
AB  - Parents' attributions for children's behavior are of interest both as a form of
      adult social cognition and as possible contributors to children's development.
      This article reviews work on the determinants and the effects of parents'
      attributions. Included in the discussion of possible determinants are
      characteristics of the target (e.g., age and sex), characteristics of the judge
      (e.g., mothers vs. fathers), and characteristics of the behavior to be explained
      (e.g., positive or negative). Included in the discussion of possible effects are
      effects on parents' affect and behavior and on children's development. The
      evidence suggests that parents do form attributions for their children's behavior
      and that these attributions vary in predictable (although not perfectly
      consistent) ways across judges, targets, and outcomes. The evidence also
      suggests, although less certainly, that attributions affect both parents'
      behavior and children's development. The review concludes with suggestions for
      future research.

PMID- 8556887
TI  - Kinship support and maternal and adolescent well-being in economically
      disadvantaged African-American families.
AB  - This study tested a conceptual model developed to explain the link between
      kinship support and the psychological well-being of economically disadvantaged
      African-American adolescents. The relation of kinship support with maternal and
      adolescent well-being and mothers' child-rearing practices was assessed in 51
      African-American families whose incomes placed them at or below the poverty
      threshold. Findings revealed that kinship social support to mothers/female
      guardians was positively associated with adolescent psychological well-being,
      maternal well-being, and more adequate maternal parenting practices (acceptance,
      firm control and monitoring of behavior, autonomy granting). Maternal well-being
      and more adequate maternal parenting practices were positively related to
      adolescent well-being. Evidence of the mediational role of maternal well-being
      and parenting practices was revealed. When the effects of maternal well-being and
      maternal parenting practices were controlled, significant relations between
      kinship support and adolescent well-being were no longer apparent.

PMID- 8556888
TI  - Family structure and psychosocial correlates among urban African-American
      adolescent males.
AB  - Substance use and delinquency, psychological well-being, and social support were
      compared across 5 family constellations among 254 urban African-American
      adolescent males. Single-mother, stepparent, both parents, mother with extended
      family, and extended family only households were studied. The only differences
      found were that youth living in single-mother households reported more parental
      support than other youth. Relationships with father and male role models were
      also studied and related to several psychosocial outcomes. The results challenge
      the assumptions that single African-American mothers are alone in providing
      support to their sons and that fathers' absence results in no significant
      relationship.

PMID- 8556889
TI  - The long-term effects of parental divorce on the mental health of young adults: a
      developmental perspective.
AB  - The effects of parental divorce during childhood and adolescence on the mental
      health of young adults (age 23) were examined, using the National Child
      Development Study (NCDS), a longitudinal, multimethod, nationally representative
      survey of all children born in Great Britain during 1 week in 1958 (N = 17,414).
      Children were assessed at birth and subsequently followed up at ages 7, 11, 16,
      and 23 by means of maternal and child interviews, and by psychological, school,
      and medical assessments. Parental divorce had a moderate, long-term negative
      impact on adult mental health, as measured by the Malaise Inventory total score,
      and controlling for economic status, children's emotional problems, and school
      performance preceding marital dissolution. The likelihood of scoring above the
      clinical cutoff of the Malaise Inventory rose from 8% to 11% due to parental
      divorce. This indicated that the relative risk of serious emotional disorders
      increased in the aftermath of divorce, but that the large majority of individuals
      did not exhibit such risks. Path analyses revealed that the negative effects of
      divorce on adult mental health operated indirectly through higher emotional
      problems and lower levels of school achievement and family economic status at age
      16. Results related to timing of divorce, remarriage, and interactions between
      age 7 emotional problems and divorce, and between age 7 emotional problems and
      child gender, are also discussed.

PMID- 8556890
TI  - The structure and coherence of competence from childhood through adolescence.
AB  - The structure and coherence of competence from childhood (ages 8-12) to late
      adolescence (ages 17-23) was examined in a longitudinal study of 191 children.
      Structural equation modeling was utilized to test a conceptual model and
      alternative models. Results suggest that competence has at least 3 distinct
      dimensions in childhood and 5 in adolescence. These dimensions reflect
      developmental tasks related to academic achievement, social competence, and
      conduct important at both age levels in U.S. society, and the additional tasks of
      romantic and job competence in adolescence. As hypothesized, rule-breaking versus
      rule-abiding conduct showed strong continuity over time, while academic
      achievement and social competence showed moderate continuity. Results also were
      consistent with the hypothesis that antisocial behavior undermines academic
      attainment and job competence.

PMID- 8556891
TI  - Behavioral precursors to accidents and resulting physical impairment.
AB  - The main goal of the study was to determine, within a model of emotional and
      behavioral regulation, if there are developmental precursors to accidents and
      resulting physical impairment. Data collected at ages 8 and 14 with 147 males and
      142 females using peer nomination and teacher rating were related to the number
      of types of accidents the subjects had been in and impairment as a result of an
      accident by the age of 27 when the subjects were interviewed on their health. The
      results showed that 44% of the men and 14% of the women had been in an accident.
      Severe effects on health were obtained for 19% of the men and 5% of the women.
      Accidents and impairment were most frequent among individuals whose behavior had
      been characterized by low emotional and behavioral control. The most generalized
      predictor of accidents and impairment was noncompliance in childhood. In
      adulthood, heavy drinking increased the risk of accidents. Aggression and conduct
      problems were the most significant precursors to male impairment, although
      several subgroups of men who were impaired were found. For females, the
      predictions of accidents and impairment were less accurate than for males.

PMID- 8556892
TI  - Children's judgements about psychological harm in social context.
AB  - 72 children, ages 6 to 11 years, were presented with a series of stories
      involving psychological harm (name-calling) in a game context. Situations were
      presented in which intentions, consequences, and game context were varied, along
      with order of story presentation. Comparison between acts of physical and
      psychological harm were also conducted. Although responses in some conditions
      were influenced by order of presentation, age differences were found in
      children's evaluations of agents' actions and recipients' reactions for
      psychological harm in game contexts. Younger children were more likely to ignore
      intentions and consequences or the recipient's perspective and to focus on
      contextual features (e.g. game rules). Older children were more likely to base
      their evaluations on intentions, or both intentions and consequences, and to take
      into account the recipient's perspective. Game context interacted differentially
      with psychological and physical harm at all ages. Evaluations of acts of physical
      harm were more likely than acts of psychological harm to be transformed by game
      context.

PMID- 8556893
TI  - Grade-level differences in the social value of effort: implication for self
      presentation tactics of early adolescents.
AB  - Differences in fourth, sixth, and eighth grade (10-, 12-, and 14-year-old)
      students' willingness to portray themselves as diligent to their popular peers
      and teachers and their perceptions of the social value of effort and ability
      ascriptions were examined. The results revealed that the fourth- and sixth-grade
      students desired to portray themselves as effortful to teachers and peers,
      whereas the eighth graders were more reluctant to convey to their popular peers
      than teachers that they study hard. Consistent with these findings, the fourth
      graders perceived high effort to increase teacher approval as well as popularity
      among peers, whereas the eighth graders viewed diligence as facilitating teacher
      approval but low effort expenditure as improving peer popularity. Reasons for
      youngsters' changing notions of the social value of achievement ascriptions and
      their self-presentation tactics in school are discussed.

PMID- 8556894
TI  - Occupational portrayals on television: children's role schemata, career
      aspirations, and perceptions of reality.
AB  - Do children's schemata for occupations they observe in real life differ from
      those they see on TV? 177 second- and fifth-graders were assigned to conditions
      in a 2 (real-life or on TV) x 2 (police officer or nurse) design. They answered
      open-ended questions about what police officers or nurses do (in real life or on
      TV) and rated the typicality of various job activities. Their schematic knowledge
      about TV and real occupations was clearly differentiated. TV versions entailed
      more glamour, higher income, more stereotypes, and more dramatic events without
      negative consequences. Real-life occupations entailed more effort, status, and
      excitement. Older children differentiated slightly more clearly than younger
      ones. Children who perceived television as factual and realistic had real-world
      schemata similar to TV images. Children who were heavy viewers and perceived
      television as realistic were most likely to aspire to jobs shown on TV.
      CONCLUSION: children form separate schemata for social information acquired from
      TV and from real-world experience, but those who perceive television as socially
      realistic are apt to incorporate TV messages in their schemata and their
      aspirations.

PMID- 8556895
TI  - Helplessness in early childhood: the role of contingent worth.
AB  - This article presents an expanded view of the bases of helpless reactions to
      failure. This view stems from recent findings of helplessness in young children.
      Previous formulations have stressed the attainment of invariant trait conceptions
      as a necessary condition for helplessness to occur and have suggested that
      children are relatively invulnerable to helplessness prior to this attainment. We
      review a series of studies documenting that key aspects of helplessness are
      present in preschool and early elementary school children (ages 4-7). We then
      propose a preliminary model in which (a) a general conception of self and (b) the
      notion of this self as an object of contingent worth are sufficient conditions
      for helplessness. We integrate this view with Dweck and Leggett's model of
      helplessness in older individuals, in which more differentiated trait conceptions
      play an important role.

PMID- 8556896
TI  - How schoolchildren propose to negotiate: the role of social withdrawal, social
      anxiety, and locus of control.
AB  - The role of social anxiety, social withdrawal, and locus of control in the
      developmental level of interpersonal negotiation strategies (INS) when resolving
      hypothetical conflicts was examined in a short-term longitudinal study (fall and
      spring). Applying a balanced design, 96 children aged 8 and 11 from 8 classes
      participated in the study. At both assessments, results indicated that sociable
      children were more likely to exhibit greater competence in INS than socially
      withdrawn children. However, both concurrent and longitudinal analyses indicated
      that degree of social anxiety tended to influence this relation. Among less
      socially anxious children, the sociable children did exhibit greater INS
      competence than those more socially withdrawn, but this relation was not revealed
      among the more socially anxious children. Finally, on the whole, children who
      showed internal locus of control were more competent at INS than children with
      external locus of control.

PMID- 8556897
TI  - A longitudinal study of the roots of preschoolers' conscience: committed
      compliance and emerging internalization.
AB  - The focus of this study is the complex relation between compliance and
      internalization in childhood. It is a replication and a longitudinal extension of
      earlier work, where we distinguished between 2 forms of compliance: committed,
      when the child eagerly embraced and endorsed the mother's agenda, and
      situational, when the child was cooperative, but lacked the sincere commitment
      and feeling of internal obligation. 99 children, seen previously at 26-41 months,
      were studied again at 43-56 months. Compliance and internalization were assessed
      in multiple observational contexts and using maternal reports. As at toddler age,
      the 2 forms of compliance had distinctly different developmental trajectories,
      and again, only committed compliance was significantly associated with measures
      of internalization. Moreover, committed but not situational compliance at toddler
      age predicted internalization at preschool age. Shared positive affect within the
      mother-child dyad at toddler age predicted some measures of internalization at
      preschool age. Further evidence of significant differences in children's
      compliance to maternal "dos" versus "don'ts" is reported.

PMID- 8556898
TI  - Frontal activation asymmetry and social competence at four years of age.
AB  - The pattern of frontal activation as measured by the ongoing electroencephalogram
      (EEG) may be a marker for individual differences in infant and adult disposition
      to respond with either positive or negative affect. We studied 48 4-year-old
      children who were first observed in same-sex quartets during free-play sessions,
      while making speeches, and during a ticket-sorting task. Social and interactive
      behaviors were coded from these sessions. Each child was subsequently seen 2
      weeks later when EEG was recorded while the child attended to a visual stimulus.
      The pattern of EEG activation computed from the session was significantly related
      to the child's behavior in the quartet session. Children who displayed social
      competence (high degree of social initiations and positive affect) exhibited
      greater relative left frontal activation, while children who displayed social
      withdrawal (isolated, onlooking, and unoccupied behavior) during the play session
      exhibited greater relative right frontal activation. Differences among children
      in frontal asymmetry were a function of power in the left frontal region. These
      EEG/behavior findings suggest that resting frontal asymmetry may be a marker for
      certain temperamental dispositions.

PMID- 8556899
TI  - Activity and behavioral development in stunted and nonstunted children and
      response to nutritional supplementation.
AB  - It is frequently assumed that undernutrition in young children leads to poor
      development through reduced activity. 3 groups of 26 1-year-old stunted children
      were studied: nutritional supplementation, supplementation with psychosocial
      stimulation, and controls. 26 nonstunted comparison children were also studied.
      Activity levels were measured by extensive observation in the homes, and
      development using 4 subscales of the Griffith's Mental Development Scales.
      Initially, stunted children were less active than nonstunted ones (p < .01), but
      after 6 months they caught up regardless of treatment. The mental ages of the
      stunted children were lower than those of the nonstunted children initially, and
      improved with either treatment. Initially, activity levels made a significant
      contribution to the variance in the locomotor subscale only, but not 6 months
      later. Activity did not predict change in development over 6 or 12 months, nor
      did change in activity over 6 months predict change in development over 12
      months.

PMID- 8556900
TI  - Do first-year intervention effects endure? Follow-up during toddlerhood of a
      sample of Dutch irritable infants.
AB  - This study evaluated the enduring effectiveness of a skill-based training program
      to enhance maternal sensitivity between 6 and 9 months of age. 82 mothers and
      their toddlers were evaluated at 18 and 24 months, and 79 at 31/2 years on the
      bases of observations of free play, everyday interaction, problem solving, and
      peer interaction. Most of the significant behavioral changes noted in the second
      year pertain to attachment security, indices of maternal sensitivity across
      situations, and child cooperation. Some enduring effects on indices of
      sensitivity appear to be attachment-mediated. In the third year, results revealed
      direct enduring intervention effects on parental responsiveness and child
      cooperation. Attachment-mediated effects were evident for maternal assistance,
      child security, and positive peer contact. Attachment pattern also predicted
      differences in attractiveness of the focal child as an interactive partner.

PMID- 8556901
TI  - Developmental and temperamental differences in emotion regulation in infancy.
AB  - One of the major adaptations during the infancy period is the development of the
      ability to cope with arousing or uncertain events. The following study was
      designed to examine emotion regulation strategy use between 6 and 18 months. 75
      infants (25 each of 6-, 12-, and 18-month-olds) were videotaped interacting with
      3 female strangers. Coping strategies were coded using a portable computer with a
      continuous sampling program, enabling coders to record both frequencies and
      durations of behaviors. Results indicated that 6-month-olds were more likely than
      12- or 18-month-olds to use gaze aversion and fussing as their primary emotion
      regulation strategies, and were less likely than the older infants to use self
      soothing and self-distraction. 18-month-olds were more likely than the younger
      infants to attempt to direct their interactions with the strangers. Infants'
      strategy use also differed as a function of their wariness of strangers,
      particularly at 12 months of age.

PMID- 8556902
TI  - Smiling and fussing in seven-month-old preterm and full-term black infants in the
      still-face situation.
AB  - We investigated emotional responses to the still-face paradigm in 7-month-old
      preterm and full-term black infants. Baby FACS criteria were used to code the
      duration and intensity of infant smiles and the presence or absence of cry faces
      and fussy vocalizations within each episode. Infants in both groups showed the
      still-face effect: a significant reduction in smiling from episode 1 (baseline)
      to episode 2 (maternal still-face) and partial return to baseline in episode 3
      (recovery). A multivariate analysis of covariance (MANCOVA) for big smiles
      yielded significant main effects for group and episode and a significant group x
      episode interaction. Preterm infants spent less time than full-term infants
      displaying big smiles in episode 1 and a less pronounced decrease in big smiles
      in episode 2. Maternal depressive symptoms did not differ significantly between
      groups. Counter to our expectations, depressive symptoms were positively
      associated with small-to-medium smiles in the baseline episode but not with big
      smiles in any episode. These findings confirm the robustness of the still-face
      paradigm and its potential usefulness for research on individual as well as group
      differences in affective communication in infants.

PMID- 8556903
TI  - Spontaneous leg movements of infants with Down syndrome and nondisabled infants.
AB  - Infants with Down syndrome (DS) represent a population in which new behaviors are
      acquired significantly more slowly than in nondisabled infants. We propose that
      infants' spontaneous movements hold a key to understanding the process of
      development--of integrating intrinsic dynamics and function. In this
      investigation, we compared the spontaneous leg movements of 10 infants with DS
      and 2 groups of nondisabled (ND) infants matched for chronological age and motor
      age. In contrast to common perceptions, we did not observe a significant
      difference in the frequency of movements between infants with DS and ND infants.
      But, infants with DS demonstrated significantly fewer of the most complex
      patterned leg movements, that is, kicking patterns. Further, the frequency with
      which both DS and ND infants kicked was significantly correlated with the age at
      which they began to walk. Biomechanical variables were identified, as well, that
      related to their emergent movement patterns. These data are consistent with
      Edelman's proposal that spontaneous movements that occur repeatedly in regions of
      the organism's functional work space facilitate the development of stable
      behavioral patterns and emphasize the role of the interaction of multiple
      subsystems in the emergence of new behaviors.

PMID- 8556904
TI  - Emerging differentiation of folkbiology and folkpsychology: attributions of
      biological and psychological properties to living things.
AB  - Research suggests that for adults, "folkpsychology" and "folkbiology" represent
      distinct conceptual domains for reasoning about living things. However, it is not
      clear whether these domains are distinct for children; past work suggests that
      the 2 systems are confused until age 10, and that radical theory change accounts
      for eventual differentiation. To examine this claim, 16 subjects each at ages 6,
      8, and adult were shown pictures of predatory and domestic animals and asked
      whether each animal displayed a variety of biological properties (e.g., has
      blood) and psychological properties (e.g., can think, can feel angry). Subjects
      at all ages showed clearly different attribution patterns for biological versus
      psychological properties. This dissociation of attribution patterns provides
      evidence that by kindergarten, notions of folkpsychology and folkbiology are
      sufficiently differentiated to constitute distinct and independent conceptual
      domains. This in turn suggests that radical theory change regarding living things
      either occurs prior to the beginning of formal education, or does not explain the
      development of folkbiological knowledge.

PMID- 8556905
TI  - Waiting to use a symbol: the effects of delay on children's use of models.
AB  - To use a symbol to solve a problem, children must achieve representational
      insight; they must realize that the symbol stands for its referent. Moreover,
      they must keep this relation in mind as they attempt to use the symbol. The
      present studies investigated the achievement and maintenance of representational
      insight. 3-year-olds were asked to use a scale model of a room to find a toy
      hidden in the room. In Study 1a, children first watched as a small toy was hidden
      in the model. They then waited either 20 sec, 2 min, or 5 min before attempting
      to find a similar, larger toy that was hidden in the corresponding place in the
      room. All children experienced all delay intervals; three groups experienced the
      delays in different orders. There was a dramatic effect of delay order. The
      children who experienced the 20-sec delay on their first trial generally
      performed well throughout the 6 trials, but the children who experienced a 5-min
      delay first almost always failed to find the toy in the room even on subsequent
      trials with shorter delays. Additional studies revealed that the negative effects
      of the initial long delay could be overcome by providing reminders of the model
      and its relevance (Studies 2 and 3) or giving children prior experience in using
      the model (Study 4). The results indicate that keeping a symbol-referent relation
      in mind can be difficult for 3.0-year-old children. This research is discussed in
      terms of the importance of maintaining representational insight.

PMID- 8556907
TI  - [Progress in intrauterine devices and research].

PMID- 8556906
TI  - What can be learned from something's not being named.
AB  - A new word-learning phenomenon is demonstrated and a new word-learning principle
      is proposed to account for it. In Study 1, 60 3-year-olds were shown a pair of
      objects and heard a novel label used repeatedly for one, but not for the other.
      In a forced-choice test of generalization of the label, the latter object was
      selected less often by the children than one that had not been present during
      training. This so-called Nominal Passover Effect was the same whether the speaker
      had completely ignored the comparison object during training or had referred to
      it with pronouns. The performance of a no-word control group (N = 24) indicated
      that the effect was not due to a preference for the less exposed of the two
      choice objects. The effect is consistent with the Exhaustive Reference Principle,
      which stipulates that whenever a new generic word is used to name something,
      expect it to be extended to all entities in a situation that the speaker
      perceives and believes to be exemplars of the name. In Study 2 (N = 48), the
      Nominal Passover Effect was replicated with 3 new sets of objects and with
      training language that contained only indefinite forms of reference. The passover
      experience was often sufficient to counteract children's tendency to generalize a
      novel label on the basis of perceptual similarity. The passover effect was not
      evident in free-choice name generalization tests in either study.

PMID- 8556908
TI  - [A study on duration of using VCu200 intrauterine device].
AB  - OBJECTIVE: To make certain of the duration of using V-copper 200mm2 intrauterine
      device (VCu200 IUD). METHODS: Six hundreds and sixty six pieces of VCu200 IUD
      used for different time period and removed for various reasons were analyzed. The
      life span of VCu200 IUD depended on corrosion, fragmentation and damage of copper
      wire and these parameters were measured on VCu200 IUD removed. RESULTS: There
      were significant difference in copper wire fragmentation rate between tenth year
      group and fifteenth year group which were 12.36%, 25.53% respectively (P <
      0.001), and so were the expulsion rate of copper wire 2.54%, 9.57% respectively
      (P < 0.05). The copper loss and copper releasing rate in tenth year-group were
      39.73%, 22.95%micrograms/day respectively. Copper corrosion resulted in
      fragmentation of copper wire which occurred the earliest in three years of use
      and expulsion of copper wire segment occurred after five years of use.
      CONCLUSION: Comparing the above results with other copper intrauterine devices,
      it was suggested that the suitable duration of VCu200 IUD use was ten years.

PMID- 8556909
TI  - [Histological study of uterine cervix during termination of early pregnancy by
      mifepristone and prostaglandins].
AB  - OBJECTIVE: To study the histological changes of uterine cervix during termination
      of early pregnancy by mifepristone and prostaglandins (PG). METHODS: A total of
      24 women who requested medical abortion was recruited. For each woman, 3 cervical
      biopsies were taken: before mifepristone treatment; 48 hours after mifepristone
      150 mg single dose treatment (i.e. immediately before PG administration); and 1
      hour after gestational sac expulsion. Specimens were studied by optical and
      electron microscopy. RESULTS: Significant collagenolysis as demonstrated by
      marked reduction and irregularity of collagen fibers, abundant accumulation of an
      amorphorous material of ground substance, and infiltration of neutrophilic
      polymorphonuclear leukocytes were shown in stroma as well as in the deep portion
      of cervix after mifepristone as compared to the samples of early pregnant cervix
      before treatment. These changes presented to a further extent after the expulsion
      of gestational sac. CONCLUSION: The changes observed were similar to previous
      reports during cervical dilatation in term delivery. The present study confirmed
      the histological cervical ripening effect by mifepristone and suggested it may be
      used as cervical ripening agent before induction of labor as well.

PMID- 8556910
TI  - [The morphologic changes of endometrial hematostatic reaction in intrauterine
      devices induced menorrhagia].
AB  - OBJECTIVE: To investigate the relationship between intrauterine contraceptive
      devices (IUD) induced menorrhagia and endometrial spiral arteriolar contractive
      function and endometrial superficial vessels thrombus formation function.
      METHODS: Sixty five subjects were admitted and divided into IUD bleeding group
      (25 cases), IUD non-bleeding group (20 cases) and IUD non-user group (20 cases).
      The samples were obtained by curettage within 24 hours prior to menstruation and
      observed under light and electron microscope. The morphologic changes of
      endometrial micro-vessels, spiral arterioles were observed and diameter of spiral
      arterioles were measured. RESULTS: Compared with IUD non-user group, the
      degenerative changes of spiral arteriolar wall were more severe and the
      dilatation of spiral arteriolar lumen was obvious especially in spongious layer.
      In IUD non-bleeding group, these changes were mild. The platelet and fibrin
      thrombus count was the highest in IUD non-bleeding group and the lowest in IUD
      bleeding group. CONCLUSIONS: These results suggested that IUD induced menorrhagia
      might correlated with poor contraction of spiral arterolars in spongious layer
      and poor thrombus formation. Mild degeneration and dilatation of spiral
      arterioles and a lot of thrombus were seen in IUD non-bleeding group, and this
      might be the cause that the mentrual blood loss in this group did not increase
      obviously.

PMID- 8556911
TI  - [Clinical experience with modified method of tubal ligation].
AB  - OBJECTIVE: To evaluate the clinical results with modified tubal ligation method.
      METHODS: From 1983 to 1992, 700 cases of modified tubal ligation operation with
      tubes cut and overlapped were performed in our hospital, and this was compared
      with 602 cases of Pomeroy's and 502 cases of modified Uchida's method. Patients
      were followed at 6 months, 2 and 5 years. Pregnancy rates, menstruation
      disturbances, lower abdominal or back pain, and leucorrhea were observed.
      RESULTS: Patients with modified tubal ligation method had a pregnancy rate of
      0.43%, which was significantly lower than that of Pomeroy's 1.50% (P < 0.05). The
      modified method group also had few complications. The occurence rate of
      menorrhage and prolonged bleeding were apparently lower than that of Pomeroy's
      too (P < 0.01). CONCLUSION: This modified tubal ligation method is more effective
      and practicable than Pomeroy's and modified Uchida's method.

PMID- 8556912
TI  - [Fetal fibronectin diagnosis of premature rupture of the amniotic membranes].
AB  - OBJECTIVE: To determine whether fetal fibronectin is a sensitive test for the
      detection of premature rupture of the amniotic membranes. METHODS: Fetal
      fibronectin by ABC immunoblotting methods were measured in samples of
      cervicovaginal secretion from 80 cases with ruptured amniotic membranes (study
      group) and 50 cases of term pregnancy (control group A). Plasma fetal fibronectin
      were examined in 30 cases of normal pregnancy (control group B). RESULTS: The
      detection rate of fetal fibronectin in the women with ruptured membranes was
      95.0%, While 6% in normal pregnancy. CONCLUSIONS: Fetal fibronectin is a
      sensitive test for detection of present of amniotic fluid. It can be used for
      diagnosis of ruptured amniotic membranes.

PMID- 8556913
TI  - [The studies of the estrogen and progesterone receptor levels in the placenta,
      fetal membrane, uteroplacental bed and myometrium in patients with prolonged
      pregnancy].
AB  - OBJECTIVE: To reveal the relation between the changes of the estrogen receptor
      (ER) and progesterone receptor (PR) levels in the target tissues and the duration
      of pregnancy. METHODS: The method combining fluorescence with hormones and
      polyspectrum-data system were used to qualitatively and quantitatively assay the
      estrogen and progesterone receptor concentrations in the placenta, fetal
      membrane, uteroplacental bed and uterine myometrium in 30 cases with prolonged
      pregnancy and 27 cases of term pregnancy. RESULTS: ER concentrations in the
      uteroplacental bed and fetal membrane of the prolonged pregnancy group were
      markedly lower than that in the term group; ER/PR values in every target tissues
      of the prolonged pregnancy were much less than that in the term group. There is a
      positive relationship between ER and PR levels in all target tissues evidently;
      and ER/PR value in the lower segment of the uterine myometrium in the group with
      uterine contraction were significantly higher than that of group without uterine
      contraction. CONCLUSIONS: The mechanisms of both prolonged pregnancy and onset of
      labour were revealed partly in this study. The cause of prolonged pregnancy is
      relatively concerned with the decline of ER levels and the ascent of the PR
      concentrations in the target tissues. Also the uterine contraction is induced by
      the increase of ER and decrease of PR.

PMID- 8556914
TI  - [Different patterns of follicular development and luteal function].
AB  - OBJECTIVE: To study the relationship between luteal function and different
      patterns of follicular development. METHODS: Different patterns of follicular
      development as observed under transvaginal B-ultrasound in 85 infertile patients
      included: (1) Ovulation from normal follicle (ONF). (2) Ovulation from two
      follicles at the same cycle (O2F). (3) Ovulation from small follicle (OSF). (4)
      Ovulation from polycystic ovaries (PCO). (5) Luteinized unruptured follicle
      syndrome (LUFS). (6) Anovulation with follicular atresia. The luteal function of
      the first 5 types was evaluated by serum and peritoneal fluid estrogen,
      progesterone levels, endometrial histology, estradiol receptor (ER) and
      progesterone receptor (PR) analyaes, and the length of luteal phase. RESULTS: The
      incidence of luteal phase deficiency (LPD): short luteal phase was 10.42%,
      retardation of endometrial development was 4.17% in ONF, no LPD in O2F, 21.42% in
      OSF, 2/3 in PCO, 3/6 in LUFS, respectively. The incidence of LPD was 14.58% in
      ONF, 56.52% in abnormal follicular development groups (OSF, O2F and LUFS) (P <
      0.005). It was found that the retardation of endometrial development was
      associated either with lowered serum P level or normal serum P but lowered ER and
      PR concentrations. The latter condition was recognized as "pseudocorpus luteum
      deficiency". CONCLUSIONS: The different patterns of follicular development may
      exert a great influence over luteal function through the different production of
      steroid hormones and their receptors.

PMID- 8556915
TI  - [An analysis of pathologic features and prognostic factors of 10 cases with
      pseudomyxoma peritonei].
AB  - OBJECTIVE: To investigate the histogenesis and the pathological features of
      pseudomyxoma peritonei and to analysis its prognostic factors. METHODS: Ten cases
      with pseudomyxoma peritonei were clinicopathologically studies, with follown-up
      at least 24 monthes. All histopathological sections and clinical data were
      reviewed. RESULTS: Seven out of 10 patients had the ovarian mucinous tumors which
      were bilateral in 5 cases (71.4%). Histopathologically, 4 of 7 cases with ovarian
      tumor were characterized by the presence of the multifocal bleeding, fragmental
      necrosis, and occasionally, the striated border on the glandular lumens. The
      mucinous epithelial cells and mucin invased into the peritonei, destroyed normal
      structure, and formed the desmoplasia. Four patients died of pseudomyxoma
      peritonei, all with extensive lesions, invasions in the peritonei, and a short
      recurrent time (mean, 12.0 monthes) after presentation. CONCLUSIONS: The
      histogenesis of pseudomyxoma peritonei is heterogenous, the presence of possible
      metastases including from the appendix, the colon and other organs. The most
      important factors of the prognosis should include the extent of initial lesions,
      the presence of invasion in the peritonei and a rapid recurrence.

PMID- 8556916
TI  - [A study on the relationship between cervical carcinoma, dysplasia and sexually
      transmitted diseases].
AB  - OBJECTIVE: To reveal the relationship between cervical carcinoma, dysplasia and
      infections of human papillomavirus (HPV) and/or chlamydia trachomatis (CT).
      METHODS: Indirect immunoperoxidase assay (IPA) was used in 99 patients with
      cervical lesions to test the specific antibody to CT in serum. At the same time,
      HPV in biopsies was determined from 40 patients with or without CT infection by
      using polymerase chain reaction (PCR). RESULTS: (1) CT infection was found in a
      significantly greater proportion in women suffering from cervical carcinoma
      (61.5%) and dysplasia (83.3%) than in those of the control group (39.5%) (P <
      0.01). (2) Under colposcopy, the incidence of white epithelium in patients
      suffering from dysplasia was 28.6% (12/42) in the CT positive group, while in the
      CT negative group the incidence was 6.5% (2/31). The incidence of white
      epithelium in patients with both CT and HPV infections was higher than that in
      patients with CT infection alone. (3) In CT positive group, the incidence of HPV
      in patients suffering from cervical cancer and from dysplasia (60%) was much
      higher than that in the CT negative group (10%). CONCLUSIONS: CT and HPV
      infections play a synergetic role in the etiology of cervical cancer.

PMID- 8556917
TI  - [Dysgerminoma of the ovary: a clinical retrospective analysis of 60 cases].
AB  - OBJECTIVE: To study the treatment methods and the prognostic factors of pure
      dysgerminoma of the ovary. METHODS: Sixty cases histologically confirmed pure
      ovarian dysgerminoma treated in our hospital, from May 1959 to Oct. 1992 were
      retrospectively analysed. Factors mainly studied were: age, symptoms, clinical
      staging and treatment methods. RESULTS: The median age of this series was 21. The
      main symptoms were abdominal mass, pain and distension. Thirty two out of 60
      cases were stage I, 2 were stage II, 5 were stage III and 21 with recurrences or
      persistence of the disease. All cases excepting one case received surgery alone
      were treated by surgery combined with external radiotherapy or chemotherapy. Nine
      cases died of the disease. The actual 5-year survival rate was 85.17%. The
      survival rate for patients with postoperative adjuvant chemotherapy is 95% and
      that for patients with radiotherapy is 76.1%; no statistic significance was
      shown. CONCLUSIONS: In pure ovarian dysgerminoma surgery combined with
      radiotherapy or chemotherapy showed high complete remission rates and excellent
      survival rates. For younger patients and those with gestation desires as well as
      patients with advanced diseases, adjuvant chemotherapy following surgery might be
      a better choice.

PMID- 8556918
TI  - [Advances in the study of mifepristone].

PMID- 8556919
TI  - [Clinical evaluation of new drugs].

PMID- 8556920
TI  - [Progress and prospectives of endoscopic therapy for diseases of the digestive
      system].

PMID- 8556921
TI  - [Clinical evaluation of serum collagen type IV in diagnosing liver fibrosis].
AB  - Serum collagen type IV (CIV) levels determined by one step sandwich EIA kit were
      compared with the serum procollagen type III (PCIII) and hyaluronic acid (HA) in
      114 patients with various liver diseases, 30 patients without liver diseases (NL)
      and 30 controls. RESULTS: serum CIV was significantly increased in chronic active
      hepatitis, liver cirrhosis and primary hepatic carcinoma. So were PCIII and HA.
      Serum CIV PCIII and HA were found to be closely related to the degree of fibrosis
      in 69 patients' liver biopsy studies, but no correlation could be found between
      these 3 markers. The sensitivity of CIV, PCIII, HA in detecting liver fibrosis
      were 73.9%, 67.4%, 67.4% with specificity of 95.7%, 91.3%, 100.0% respectively.
      The early diagnostic value of CIV is better than PCIII and HA; their combination
      could further raise the diagnostic sensitivity to more than 90.0%.

PMID- 8556922
TI  - [Endoscopic mucosectomy for resection of early gastric cancer and precancerous
      lesions].
AB  - The authors collected 14 cases of early gastric cancer located in the mucosa and
      precancerous lesions which were resected with endoscopic mucosectomy. These
      lesions were as follows: 6 cases were early cancer (IIc type: 4 cases; IIa type:
      2 cases); 3 cases were severe dysplasia; 5 cases were adenoma, Yamada I type. The
      size of all the lesions was less than 20mm. Four cases of early gastric cancer
      were resected completely. Two cases were resected incompletely, but radical
      gastrectomy was performed one month after endoscopic mucosectomy. All the three
      cases of severe dysplasia had complete resection. But two of them received
      resection twice. Five cases of adenoma were also resected completely. The
      criteria of complete endoscopic resection were those reported in the Japanese
      literature. All cases have been followed up for 4-41 months; endoscopic and
      histological studies showed that there were no residual and recurrent cancer
      cells. The complete resection rate was 85.7% (12/14). The results suggest that
      endoscopic mucosectomy can be applied to the patients with early gastric cancer
      located in the mucosa and precancerous lesions less than 20mm in size, which can
      be resected completely. This method is safe, entails less complications and is
      especially suitable for the old and weak patients.

PMID- 8556923
TI  - [Clinical application of endoscopic injection of medication for stopping gastric
      bleeding].
AB  - The authors studied 40 patients with bleeding from peptic ulcer or gastric
      carcinoma, and evaluated the therapeutic effects of endoscopic injection of
      absolute alcohol and Bathroxobin. Among them, 20 patients were given absolute
      alcohol and the remaining 20 Bathroxobin (Reptilase). Absolute alcohol was
      injected submucosally at 4-6 pinpoints around the bleeding site (0.1-0.2ml/dose,
      total dose 0.5-1.2ml); Bathroxobin was injected similarly (1 kU/dose, total dose
      0.5-1.0kU). Treatment failed in one patient receiving alcohol because of spouting
      artery bleeding and surgery was resorted to finally. The other 39 patients had
      successful stopping of the bleeding in one time. The effective rate is 97.5
      percent (39/40) and the rate of re-bleeding is low. It is thus shown that
      endoscopic submucosal injection of absolute alcohol and Bathroxobin for stopping
      gastric bleeding is safe, simple and effective. However, more experience is
      needed in this respect.

PMID- 8556924
TI  - [The diagnostic significance of rheumatoid factors in patients with early
      rheumatoid arthritis].
AB  - The early phase of rheumatoid arthritis has attracted increasing attention due to
      the concern with prognosis of the disease. In this study IgM rheumatoid factor
      (RF) and IgA immunoglobulin were measured twice a year in 96 patients. Their
      joint damage was assessed yearly with radiographic examination. Radiological
      abnormalities detected included osteoporosis, bone erosion and joint space
      narrowing. The patients were followed up for three years. The changes of joint
      damage might be of three types: worsening, nonchange and improvement. A
      significant correlation between the levels of IgM RF and IgA immunoglobulin and
      disease activity was observed. A high level of IgM RF was prognostic for a more
      severe disease. One patient with 7 g/L IgA immunoglobulin exhibited considerable
      joint damage progression in a year, while 2 cases with minor IgA immunoglobulin
      showed remarkable improvement. These two parameters can be considered the
      important laboratory indicators for the early disease. The results may also be
      applied to guide second line antirheumatic drug therapy.

PMID- 8556926
TI  - [Thoracoscopy in persistent or recurrent spontaneous pneumothorax].
AB  - To assess the value of thoracoscopy in spontaneous pneumothorax, the procedure
      and results of thoracoscopy by using fiberoptic bronchoscope and rigid cold-light
      thoracoscope in 50 patients with persistent or recurrent pneumothorax were
      reported. We found subpleural blebs or bullae in 35 cases and adhesions
      preventing lung expansion in 10 cases. The histologic diagnosis following
      thoracoscopic biopsy in 13 patients showed non-specific inflammation in 12 cases
      and tuberculosis in one case. The overall diagnostic rate was 92% (46/50). 5
      cases were cured with transendoscopical Nd-YAG laser cauterisation of the blebs
      or bullae not exceeding 1 cm in diameter. There were no side effects after the
      procedure, and no recurrence was observed in a follow-up of 24 months. 40
      patients were treated with intrapleural talcum power under thoracoscopic control.
      The postoperative complications were transient fever and chest pain and
      recurrence was observed in two cases only (5%) during 2-7 years of follow-up. It
      is concluded that thoracoscopy enables accurate assessment of the causes of
      pneumothorax, talc pleurodesis is a very effective method of controlling
      recurrent and persistent pneumothorax, and laser therapy can play an important
      role in selected patients with spontaneous pneumothorax.

PMID- 8556925
TI  - [Value of dobutamine technetium-99m-MIBI SPECT in detecting coronary artery
      disease].
AB  - The value of dobutamine 99mTc-MIBI SPECT (Dobu-ECT) for detecting coronary artery
      disease (CAD) was assessed in 39 patients. Compared with coronary angiography,
      the overall sensitivity and specificity of Dobu-ECT for detecting CAD were 92.9%
      and 90.9%. Of 13 patients with CAD without myocardial infarction, the sensitivity
      of Dobu-ECT was 84.6%. In detecting CAD with single, double or triple vessel
      diseases, the sensitivity of Dobu-ECT was 90.9%, 87.5% and 100% respectively.
      Furthermore, 88.2% of the patients (15/17) with multivessel (two or three
      vessels) diseases were correctly identified as having multivessel involvement.
      For detecting CAD, the sensitivity and specificity of dobutamine ECG were 53.5%
      and 82%. No serious side effects were observed in the study. The results showed
      that Dobu-ECT is a feasibie, safe and noninvasive method for diagnosing CAD.

PMID- 8556927
TI  - [Detection of replicative form of HCV RNA in peripheral blood leukocytes and its
      clinical significance].
AB  - Nested RT-PCR, done by using degenerated primer pair, was used to detect
      hepatitis C virus RNA (HCV RNA) in serum, plasma, liver and peripheral blood
      leukocytes (PBLC) of 30 patients with acute and chronic posttransfusion hepatitis
      C and 7 asymptomatic anti-HCV positive subjects. The results showed that the
      percentage of positive HCV RNA in PBLC, including both the plus and minus
      strands, in patients with chronic hepatitis C was significantly higher than that
      in acute hepatitis C and asymptomatic anti-HCV positive subjects (P < 0.05
      0.001). All the 7 asymptomatic anti-HCV positive subjects did not have detectable
      minus strand of HCV RNA in their PBLC, serum or plasma. In 17 patients who had
      liver histologic examination, the positive rate of both strands of HCV RNA in
      PBLC of acute hepatitis (AH) was lower than that of chronic active hepatitis
      (CAH) (P < 0.05). Both strands of HCV RNA were detected in the liver of one AH
      and 6 CAH patients. The present data confirmed that PBLC of patients with
      hepatitis C were indeed infected by HCV. The longer the infection time, the more
      the chance of PBLC being infected by HCV. Patients with active liver disease
      (CAH) had usually higher positive rate of minus strands of HCV RNA in PBLC. In
      the serum and plasma of all the 37 cases, minus strand of HCV RNA was not
      detected and the positive rate of the plus strand of HCV RNA in their serum and
      plasma was similar. Futhermore, the positive rate of both plus and minus strands
      of HCV RNA in PBLC of 30 patients with chronic hepatitis C was also similar. It
      is suggested that HCV not only may infect PBLC, but also replicate in PBLC and
      that the occurrence of minus strand of HCV RNA is associated with activity of
      liver disease.

PMID- 8556928
TI  - [Analysis of the multidrug resistance MDR1 gene expression in clinical leukemia
      with RT-PCR].
AB  - The method of reverse transcription coupled with polymerase chain reaction (RT
      PCR) has been used to detect multidrug resistance gene MDR1 expression in 73
      leukemia patients. Specificity of MDR1 PCR product was identified by a probe
      labelled with biotin. In this paper, beta 2M mRNA (a 120bp of PCR product) was
      selected as an internal control for semi-quantitative analysis of MDR1 mRNA (a
      157bp of PCR product). Detection of MDR1 expression was positive in 31 of the 73
      patients with leukemia. The percentage of MDR1+ and the value of MDR1/beta 2M in
      the relapsed acute leukemia and CML in blast crisis were 76.00% and 0.798 +/-
      0.266, they were significantly higher than those in newly diagnosed acute
      leukemia (25.00% and 0.386 +/- 0.128) and complete remission leukemia (25.00% and
      0.151 +/- 0.059), MDR1/beta 2M in newly diagnosed was significantly higher than
      that in complete remission. We found that MDR1 gene expression correlated well
      with response to chemotherapy in 53 cases of acute leukemia. The refractory rate
      in patients with MDR1+ was 75.00%, while it was 15.00% in MDR1- (P < 0.01). We
      thought that the determination of MDR1 expression level in acute leukemia could
      provide a valuble information for designing chemotherapeutic regimen in
      individual patient, and a high level of MDR1 expression correlated closely with
      drug resistance in clinical leukemia chemotherapy.

PMID- 8556929
TI  - [Differential diagnosis of delayed encephalopathy induced by anthelmintic
      imidazoles].
AB  - Anthelmintic imidazoles induced delayed encephalopathy (AIIDE) is frequently
      encountered and has usually been misdiagnosed as sporadic encephalitis of unknown
      cause (SEU). This study was carried out to facilitate differentiation of the two
      diseases. The records of 202 cases of AIIDE were reviewed and the clinical
      features analyzed. As a results, 7 diagnostic criteria for AIIDE were proposed as
      follows: (1) history of exposure to anthelmintic before the onset; (2) presence
      of a latent period of of 2 to 5 weeks; (3) onset of the disease acute or
      subacute; (4) presence of neuropsychiatric symptoms and signs resulted from
      multifocal cerebral damage; (5) Fulfillment of two of the following conditions;
      (a) subinflammatory change in CSF with elevation of IgG; (b) diffuse slow waves
      in EEG during early stage; (c) characteristics of acute demyelinating
      encephalopathy in brain biopsy; (6) good therapeutic effect of adrenal
      corticosteroids; (7) exclusion of other neuropsychiatric disorders in a fallow-up
      period of one year. AIIDE is a new disease entity and its diagnosis is mainly
      based on the clinical features. EEG, CT or MRI are important diagnostic measures,
      but history of exposure to anthelmintic is the most important criterion.
      Multifocal hemorrhagic leukoencephalopathy is its main pathologic feature.

PMID- 8556930
TI  - [Endoscopy for digestive system after acute myocardial infarction].

PMID- 8556931
TI  - [Progress in the study on immunogenetics of systemic lupus erythematosus].

PMID- 8556932
TI  - [Prospect and retrospect of women's health service in China].

PMID- 8556933
TI  - [Studies on comprehensive evaluation of toxic hazard in low-concentration benzene
      pollution].
AB  - Early adverse effects of exposure to benzene in a concentration less than 32
      mg/m3 on the employees' health were comprehensively evaluated with WHO
      neurobehavioral core test battery, cytokinesis-block micronucleus assay for
      peripheral blood lymphocytes, determination of serum level of sialic acid and T
      lymphocyte assay with alpha-naphthyl acetate esterase (ANAE) stain. Results
      revealed emotional irritability could be found in the exposed employees and 24%
      of them showed an abnormal percentage of micronuclei formation and increased
      serum level of sialic acid.

PMID- 8556934
TI  - [Dynamics of blood lead level in exposed workers and its effects on fetal
      constitutional development].
AB  - Levels of blood lead (Pb-B) and zinc protoporphyrin (ZPP) in exposed women of a
      storage battery plant during their early gestation and delivery stage were
      determined and compared with those in control women. Pb-B in exposed women kept
      in a consistently high level of 0.98 mumol/L and ZPP of 1.35 mumol/L. Pb-B level
      in umbilical cord of their neonates reached 0.90 mumol/L and ZPP 1.11 mumol/L,
      both of which were significantly higher than those in control women (0.26 mumol/L
      and 0.34 mumol/L of Pb-B and 0.51 mumol/L and 0.78 mumol/L of ZPP in women's
      blood and umbilical cord blood, respectively). The significance of consistent
      increase in Pb-B and ZPP and their effects on fetal development were discussed in
      the paper.

PMID- 8556935
TI  - [Prevalence of obesity in Hong Kong children and adolescents aged 3-18 years].
AB  - A cross-sectional study on growth and development in Hong Kong children and
      adolescents ranging from their birth to 18 years of age was performed in 1993 and
      all the growth standards were constructed in the form of percentile chart. Those
      having a weight at one's median weight for height standard of 120% were defined
      as obesity. Prevalence of obesity in children and adolescents aged 3-18 was
      10.08% (11.28% and 8.93% for boys and girls, respectively), which was higher than
      that in the inland of the country and that in Hong Kong as previously reported.
      Result showed there was a gradual increase in the prevalence after the age of 5,
      which reached a peak at the age of 11 for boys and 8 for girls.

PMID- 8556936
TI  - [Isolation of fusarium and extraction of its toxin from buckwheat grown in an
      area with "endemic breast enlargement" disease].
AB  - Fusarium was isolated and its toxin was extracted from the buckwheat grown in an
      epidemic area with "endemic breast enlargement" disease. The toxin was determined
      with thin layer chromatography and mass spectrography. Results showed there were
      more than four kinds of mould, including fusarium, isolated from buckwheat grown
      in the endemic disease area. All the buckwheat grown in the area were infected
      with mould and 34% with fusarium. Three kinds of toxin were extracted from the
      buckwheat, with rates of flow of 0.23, 0.47 and 0.90, respectively, in thin layer
      chromatography. And, zearalenone was extracted from the buckwheat and identified
      by mass spectrography.

PMID- 8556937
TI  - [Determination of sterigmatocystin in cancerous tissues, blood and urine in
      patients with liver and stomach cancer].
AB  - Sterigmatocystin (ST) was determined with modified Southern-Western blot and
      indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) for 28
      specimens of cancerous tissues, 13 of blood and 20 of urine in 14 patients with
      liver and stomach cancer. Results showed DNA-ST adduct was detected in 14
      specimens of cancerous tissues and/or pericancerous tissues. ST values were
      higher in four of 13 patients (65-113 micrograms/kg), as compared only in one of
      14 healthy persons (68 micrograms/kg). And, ST values all were very low in urine,
      with a maximum of 13 micrograms/kg.

PMID- 8556938
TI  - [Effects of selenium and vitamin E on arachidonic acid metabolism in experimental
      myocardial ischaemia].
AB  - Wistar rats were fed with grain produced in the areas prevalent of Keshan
      Disease, and supplemented by selenium (Se) and vitamin E (VE) for ten weeks, and
      an acute myocardial ischaemia animal model was established by ligation of left
      anterior descending coronary arteries. Results indicated activities of
      phospholipase A2 (PLA2), creatine kinase (CK) and lactate dehydrogenase (LDH),
      and levels of arachidonic acid (AA), thromboxane A2 (TXA2), leucotriene C4 (LTC4)
      and lipid peroxides (LPO) increased, but level of prostacyclin (PC) and
      activities of glutathione peroxidase (GSH-PO), copper-zinc superoxide dismutase
      (Cu-Zn-SOD) and catalase (CAT) decreased 48 hours after ligation of the coronary
      vessels in rats without supplement of Se and VE. Supplement of Se or VE in their
      feed could reverse the above effects and the best results could be got by
      supplement of both. It suggested that supplement of adequate amount of Se and VE
      in their feed could affect metabolism of AA and levels of its metabolites,
      improve myocardial function and metabolic status and reduce myocardial damage in
      rats under the stress of acute myocardial ischaemia.

PMID- 8556939
TI  - [Genetic epidemiological studies on male lung cancer].
AB  - Data of nuclear families of 194 male proband with lung cancer and 176 controls
      were analyzed to study its genetic etiology in Xuanwei County of Yunnan Province.
      Results showed risk of lung cancer in the relatives (parents and siblings) of the
      proband was 1.78 times as of controls, with a statistically significant
      difference, and risks in parents and female relatives of the proband were 2.90
      and 2.43 times as in controls, respectively, both with a statistically
      significant difference. Heritability of male lung cancer was 24.68%. It indicated
      genetic susceptibility to lung cancer in females was higher than that in males
      and played an important role in the etiology of lung cancer.

PMID- 8556940
TI  - [National notification of incidence of chronic occupational poisoning during 1984
      1993].
AB  - Incidence and distribution of chronic occupational poisoning caused by toxic
      chemicals during 1984 to 1993 throughout the country were summarized and
      analyzed. Totally, 28,901 cases of chronic occupational poisoning were notified
      during this period. Lead, benzene and trinitrotoluene were three major toxic
      chemicals which caused poisoning, with chronic lead poisoning listed the first
      place, accounting for 47.5% of the total cases. Most of the cases distributed in
      Laioning, Hunan and Jiangsu Provinces, and 75.4% of the cases occurred in
      machinery, chemical, metallurgical, non-ferrous, light industries, etc. Incidence
      of poisoning presented a decreased trend during the past 10 years and the reason
      of it was described in the paper. The authors indicated that quality assurance in
      notification of occupational diseases depended on regular implementation of the
      work in prevention and treatment of occupational diseases.

PMID- 8556941
TI  - [Quantitative diagnosis of dust-macule type pneumoconiosis].
AB  - Simulated diagrams of lung sections of dust-macule type pneumoconiosis were
      plotted with computer simulation techniques and classification criteria for dust
      macule volume density were formulated with stereologic quantitative analysis to
      differentiate the effects of artificial factors in pathological diagnosis of
      pneumoconiosis, Areas of dust-macule of 100%, 75% and 50% corresponded to 41.4,
      31.0 and 20.7 in dast-macule density, respectively. The pathological diagnostic
      criteria for pneumoconiosis were evaluated by standardized chest X-ray film with
      a satisfactory result. It is suggested a squared test grid with a length of 5 mm
      in each sides of the small checks be used in practice.

PMID- 8556942
TI  - [Studies on biological indicator values in diagnosis for lead poisoning].
AB  - Blood lead levels, urine lead levels, indicators of porphyrin metabolism and
      other biological indicators were determined in 330 workers exposed to lead and
      100 unexposed controls with national standardized methods for quality assurance.
      Data were analyzed with modern statistical methods in a microcomputer with SAS
      software. Criteria values for blood lead and urine lead were formulated with
      curve fitting and discriminant analysis, and local normal upper limit values were
      1.43 and 0.25 mumol/L for blood lead and urine lead, respectively, acceptable
      upper limit values 1.93 and 0.35 mumol/L, respectively, and diagnostic values for
      poisoning 3.02 and 0.56 mumol/L, respectively. Correlation between workplace air
      lead concentrations and biological indicators, between blood lead levels and
      other indicators, and their specificity, sensitivity, accuracy and underdiagnosis
      and misdiagnosis were evaluated at the same time to provide a reference database
      for revising the national diagnostic criteria for lead poisoning.

PMID- 8556943
TI  - [Advances in the study of industrial women's hygiene in China].

PMID- 8556944
TI  - [Advances in the research on nucleic acid vaccines].

PMID- 8556945
TI  - [Advances in the study on biological effects of diesel exhaust].

PMID- 8556946
TI  - Measurement of apoptotic cells in peripheral blood.
AB  - The measurement of apoptosis in peripheral blood might represent a useful tool in
      acquired immunodeficiency syndrome (AIDS) and cancer research. Among the many
      assays that are currently used to identify apoptotic leukocytes, flow cytometric
      methods are the most valuable in terms of rapidity, simplicity, and level of
      analytical detail. Some flow cytometric assays may also offer the additional
      advantage of detecting the earliest phases of apoptosis, which is paramount
      importance for measuring apoptotic cells in vivo before they are destroyed by
      phagocytes.

PMID- 8556947
TI  - DNA analysis of in situ ductal carcinoma of the breast via flow cytometry.
AB  - Flow cytometric (FCM) DNA analysis of 41 clinical cases of ductal carcinoma in
      situ (DCIS) of the breast was performed on fine-needle aspirates of unfixed,
      frozen tissue. Based on analysis of a single tissue sample, abnormal DNA content
      was found in 35 (85%) of the cases, and 15 (37%) disclosed heterogeneity. If five
      or more samples were analyzed, then heterogeneity was found in eight of ten
      cases. No conclusive correlation could be found between DNA index (DI) and
      histopathology. Our results on DCIS demonstrate a very high concordance with
      invasive breast cancer with respect to the frequency of DNA nondiploid cases,
      distribution of DI, occurrence of multiple clones, and S-phase fraction. This
      indicates that major genetic alterations and DNA heterogeneity are early events
      in carcinogenesis that are already established at the preinvasive stage.

PMID- 8556948
TI  - Contribution of ploidy and cell kinetics from fine-needle aspirates for the
      diagnosis of breast lesions: study of 606 consecutive cases.
AB  - A total of 606 consecutive patients with palpable breast lesions underwent
      physical examination, mammography, and fine-needle aspiration for cytologic and
      flow-cytometric (FCM) DNA analyses. FCM determinations included DNA ploidy and
      the fraction of cells in S + G2 + M phases. Aneuploid clones were considered
      indicative of malignancy; diploid, rapidly proliferating (S+G2+M>12%) clones were
      considered suggestive of malignancy; and diploid, slowly proliferating clones
      were considered indicative of benignancy. Sensitivity, specificity, and the
      predictive accuracy for positive or negative results of FCM information were 82%,
      90%, 93.1% and 69.8%, respectively. These values were lower than those observed
      for the three conventional diagnostic assays owing to the presence of false
      positive results (in 23 cases) or unassessable DNA plots (in 90 cases). FCM
      information alone detected five cases in which the other tests gave inconclusive
      results and in association to the conventional diagnostic triple test, increased
      the incidence of positive conclusive cases from 97.9% to 99.2%. However, further
      refinements are needed before this approach can be used as a routine diagnostic
      tool.

PMID- 8556949
TI  - Comparison of flow and image cytometry for DNA content analysis of fresh and
      formalin-fixed, paraffin-embedded tissue in breast carcinoma.
AB  - DNA ploidy and S-phase fraction are considered to be prognostic variables in
      breast carcinoma. DNA content of 35 cases of breast carcinoma of varying
      histologic types and nuclear grades was analyzed by flow cytometry and image
      analysis in both fresh and formalin-fixed, paraffin-embedded tissue. Fresh cell
      and deparaffinized nuclear suspensions were used for flow cytometry. Fresh and
      deparaffinized tumor tissue samples were used for image analysis. The results of
      analysis for DNA ploidy, DNA index of DNA aneuploid Go/G1 peaks, and S-phase
      fraction were compared in different tissue preparations for both techniques. The
      two techniques produced comparable DNA ploidy results with both fresh and
      formalin-fixed, paraffin-embedded tissue. Sensitivity for detection of DNA
      aneuploidy was somewhat greater by image analysis, particularly in deparaffinized
      tissue. There was 89% agreement in detection of DNA aneuploidy by flow cytometry
      in fresh and paraffin-embedded, formalin-fixed tissue; the coefficients of
      variation of the DNA diploid Go/G1 peaks were much wider in the latter. In image
      analysis there was 91% agreement between fresh and fixed specimens. Agreement
      between the flow cytometry and image analysis in fresh specimens was 91%; in
      deparaffinized nuclear suspensions it was 94%. There is a high degree of
      correlation between the values of DNA index of DNA aneuploid Go/G1 peaks; the
      estimates of S-phase fraction are much more variable. Results also show a good
      correlation of the DNA ploidy with the nuclear grades.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8556950
TI  - Pan cycle expression of proliferating cell nuclear antigen in human colorectal
      cancer and its proliferative correlations.
AB  - Proliferating cell nuclear antigen (PCNA) is a key cycle regulatory protein of
      known structure and function that also has an important role in DNA repair, its
      use as a marker of proliferation can be assessed directly using a thymidine
      analogue in suitably labelled pathological material. Following optimisation
      studies, a quantitative and cell cycle phase-specific analysis of PCNA expression
      in fresh biopsies from 50 colorectal tumours (Series A) was undertaken using dual
      parameter flow cytometry (FCM). For comparison, quantitative histometric studies
      of PCNA expression were undertaken on 50 archival bromodeoxyuridine (BrdUrd)
      labelled colorectal tumours (Series B). In FCM assays, PCNA-specific fluorescence
      was displayed throughout the cell cycle in both cells and nuclei under all
      preparation conditions, but to a very variable extent. The mean PCNA labelling
      index ranged from 38.7% to 53.0% according to the method of cell extraction used.
      In the 27 diploid tumours in Series A, the median PCNA LI in G0/G1 was 71.5%
      (range 27.0-90.6%), in S it was 10.5% (3.3-29.5%), and in G2/M it was 17.4% (5.7
      43.5%). In the histometric studies of Series B tumours, the mean [S.D.] PCNA
      labelling index (LI) was 38.8 [9.8]%, compared with the BrdUrd (histometric) LI
      of 21.1 [9.0]%. The BrdUrd LI measured by FCM was 12.4 [6.5]%. PCNA-PC10 is
      expressed throughout the cell cycle in human colorectal tumour biopsies, which is
      in keeping with the range of DNA repair, synthesis, and regulatory functions that
      it is now recognised to perform throughout the cell cycle.

PMID- 8556951
TI  - Standardization of absolute CD4+ lymphocyte counts across laboratories: an
      evaluation of the Ortho CytoronAbsolute flow cytometry system on normal donors.
AB  - The Ortho CytoronAbsolute is a flow cytometer designed to provide direct absolute
      counts of lymphocytes and their subsets from a single instrument. This study was
      designed to determine the performance of four geographically separated
      CytoronAbsolute instruments using 24-h-old, shipped, whole blood samples and to
      compare the results obtained on the CytoronAbsolute to those obtained using
      combinations of hematology instruments and other flow cytometers. The absolute
      count feature of the CytoronAbsolutes located at the four sites were cross
      calibrated and gave across-site coefficients of variation (CVs) of <4.0% for
      absolute count and 8.2% for absolute lymphocyte count. The calibration was stable
      for at least 2 months. Absolute lymphocyte counts and lymphocyte percentage
      immunophenotypes were determined on blood from 50 healthy human immunodeficiency
      virus (HIV)-seronegative donors. There were no significant site-to-site
      differences (each P > .05) in CD3+/CD4+ absolute lymphocyte counts determined on
      the CytoronAbsolute. In contrast, there was a significant site-to-site difference
      (P < .001) between sites 2 and 3 and sites 3 and 4 in the absolute CD3+/CD4+
      lymphocyte counts determined via the conventional method of combining a flow
      cytometry-derived percentage with a hematology instrument-derived lymphocyte
      count. There was no significant difference (P = .388) in CD3+/CD4+ lymphocyte
      percent determinations between the CytoronAbsolute and the FACScan or Profile II
      flow cytometers used in this study. These results demonstrate that different
      operators can cross calibrate CytoronAbsolutes for absolute CD3+/CD4+ lymphocyte
      subset determinations, even over large geographic distances.

PMID- 8556952
TI  - Peripheral gamma delta T-cell populations in HIV-infected individuals with
      mycobacterial infection.
AB  - Previous studies have suggested that gamma delta T cells can be increased in HIV
      1-seropositive individuals, although characterization of gamma delta T cell
      subtypes and correlation with clinical status of these patients have not been
      performed. We investigated groups of HIV-seropositive persons to determine the
      prevalence of elevated levels of gamma delta T cells and whether any gamma delta
      T cell subtypes were preferentially expressed. Since a large proportion of human
      gamma delta T cells appear to be reactive to proteins encoded by mycobacteria, we
      also examined our patients for the incidence of mycobacterial infection. Our
      results show that a significant number of HIV-positive patients have an elevated
      number of gamma delta T cells in their peripheral blood as compared to normal
      controls. HIV-seropositive patients with clinical or laboratory evidence of
      mycobacterial infection had statistically significant increases in the percentage
      and total numbers of gamma delta T cells over the HIV-positive persons without
      mycobacterial infection. An examination of the subtypes of gamma delta T cells
      revealed that certain subtypes such as V gamma 9+ and V delta 2+ T cells were
      preferentially elevated in the mycobacteria-positive patients. These results
      suggest that an increased number of gamma delta T cells in HIV-positive patients
      is most often seen in the setting of an opportunistic mycobacterial infection and
      that specific gamma delta T cell subtypes are stimulated under these conditions.
      The role of these increased number of gamma delta T cells in HIV-associated
      disease is unclear but is likely a component of the response and degree of host
      resistance to this organism.

PMID- 8556953
TI  - Clinical, biological, and immunophenotypical characteristics of B-cell chronic
      lymphocytic leukemia with trisomy 12 by fluorescence in situ hybridization.
AB  - The clinical, biological, and immunophenotypical characteristics of B-cell
      chronic lymphocytic leukemia (B-CLL) patients with trisomy 12 detected by
      fluorescence in situ hybridization (FISH) using a chromosome 12 alpha-centromeric
      probe (D12Z3) were analyzed in the present study. From a total of 104 consecutive
      B-CLL patients, 21 (20%) displayed trisomy 12, the percentage of trisomic cells
      ranging from 13% to 76%. From the clinico-biological point of view, patients with
      trisomy 12 were associated with atypical CLL morphology (43% vs 10%, P = 0.04)
      and BM diffuse pattern (75% vs. 25%, P = 0.02) together with increased WBC counts
      (141 +/- 220 vs. 58 +/- 67 x 10(9)/L, P = 0.04). In contrast, no association was
      detected between the presence of trisomy 12 and other disease characteristics
      such as age, sex, clinical stage, hepatomegaly, lymphadenopathies, haemoglobin
      levels and platelet counts, and the cell cycle distribution of PB leukocytes in
      both groups of patients. Trisomy 12 patients had a significantly higher
      expression of the FMC7 antigen both in percentage (34 +/- 34% vs. 13 +/- 20%, P =
      0.02) and absolute numbers (29 +/- 62 vs. 7 +/- 17 x 10(9)/L, P = 0.007). No
      major differences were found regarding the expression of mouse rosettes, CD19+,
      and CD19+/CD5+ lymphocytes. Upon analyzing the correlations between the disease
      characteristics of trisomy 12 cases, significant associations were found between
      the percentage of trisomic cells and both the WBC count (r = 0.52, P = 0.02) and
      the PB lymphocyte count (r = 0.60, P = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556954
TI  - CD43 and CD5 antibodies define four normal and neoplastic B-cell subsets: a three
      color flow cytometric study.
AB  - CD43 antibodies are best known for identifying normal and neoplastic T cells and
      a subset of neoplastic B cells in paraffin sections. The frequency of
      nonneoplastic CD43 + B cells in different reactive settings, the proportion of B
      cell neoplasms with small CD43+ populations, and the relationship of CD43+ B
      cells was therefore studied in 138 specimens using three-color cytometric
      analysis. CD43 and CD5 defined four normal B-cell subsets (CD43 + CD5 +, CD43 +
      CD5-, CD43 - CD5+, and CD43-CD5-). A significantly greater proportion of CD43+ B
      cells was found in cord blood and putative HIV+ blood samples than in normal
      control bloods. B-cell neoplasms derived from each of these four B-cell subsets
      were identified, with CD43+ /CD5+ and CD43-/CD5- neoplasms being most common. The
      predominant B-cell population coexpressed CD43 alone in 2/39 neoplasms and CD5
      alone in four. A minority of cases showed heterogeneous CD43 expression. The B
      cells in two of three posttransplant lymphoproliferative disorders coexpressed
      CD43. B cells showed weaker CD43 staining than did T-cells (relative fluorescence
      0.38 +/- 0.29). These findings support the concept that CD43 expression by
      neoplastic B cells is not an aberrant finding. CD43 expression on normal and
      neoplastic B cells is independent of CD5 expression even though CD43 and CD5 are
      frequently coexpressed. CD43 expression by B cells sometimes might be
      underestimated in paraffin sections because it is much weaker than on T
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8556955
TI  - Instrument-dependent fluorochrome sensitivity in flow cytometric analyses.
AB  - Flow cytometry has become the preferred technique by which critical clinical
      evaluations are made such as CD4 counts and aneuploid analyses. Mounting concern
      has arisen over the numerous techniques, reagents, and different flow cytometric
      employed to determine these data. Several studies have documented significant
      differences in results when different flow cytometers are utilized to analyze the
      same sample. Fluorochrome-dependent instrument sensitivity also has been reported
      by numerous investigators. As more and more procedures are performed by
      cytometric analysis, light scatter and fluorescence limitations, which appear to
      be instrument dependent, demonstrate that not all flow cytometers have the same
      capabilities. Attempts were made to calculate molecules of equivalent soluble
      fluorochrome (MESF) values on nine different flow cytometers using fluorescein
      isothiocyanate (FITC) and R-phycoerythrin (R-PE) labeled microsphere reference
      standards produced by Flow Cytometry Standards Corporation (FCSC). Dramatic
      differences were observed in the ability of some cytometers to resolve these
      microspheres. The diminished resolution appeared to be instrument model and
      fluorochrome dependent. We propose that diminished fluorescence resolution in
      certain flow cytometers could be responsible for significant variability in
      clinical values reported from laboratories utilizing different flow cytometers.

PMID- 8556956
TI  - B-cell prolymphocytic leukemia expressing discordant myeloid-associated antigens
      in simultaneous specimens from bone marrow and peripheral blood.
AB  - The case of a 73-year-old man with B-cell prolymphocytic leukemia (PLL) and rapid
      clinical demise is reported. Flow cytometric immunophenotyping results of
      specimens obtained from the patient demonstrated a monoclonal CD5 positive B-cell
      population with myeloid-associated marker expression, which was discordant: CD15
      and CD11b were expressed in bone marrow leukemic cells, whereas peripheral blood
      leukemic cells showed virtually no expression of these markers. Discordant
      immunophenotyping results between bone marrow and peripheral blood cells have
      been reported recently. Additionally, investigators have associated expression of
      CD13 and CD11b by chronic B-cell lymphoid leukemias with a more aggressive
      clinical course and shorter survival. Expression of these myeloid-associated
      antigens by B-cell prolymphocytes in PLL has not been widely reported.
      Cytogenetic analysis revealed a karyotype of 46,XY/?44,XYdel(1q),del (3p),
      whereas molecular genetic studies demonstrated immunoglobulin gene rearrangements
      in both heavy and light chain regions. Cytochemical staining for PAS (periodic
      acid-Schiff), nonspecific esterase and methyl-green-pyronin was positive in
      leukemic cells.

PMID- 8556957
TI  - Amplification and detection of a Y-chromosome DNA sequence by fluorescence in
      situ polymerase chain reaction and flow cytometry using cells in suspension.
AB  - A procedure for amplifying and detecting nucleic acid sequences in situ using
      cells in suspension and flow cytometry has been developed. The process involves
      the use of the polymerase chain reaction (PCR) and a fluorescent in situ
      hybridization (FISH) protocol developed in our laboratory to detect the amplified
      PCR product. For these studies, a Y-chromosome specific repeat DNA sequence was
      amplified. Daudi cells, a B-cell lymphoma culture line established from a male,
      was used as a positive control and HL-60, a promyelocytic leukemia culture line
      established from a female, was used as a negative control. During the in situ PCR
      process cellular autofluorescence (noise) increases causing markedly reduced
      detection sensitivity of the probe (signal) bound to the amplified product within
      the positive cells. An autofluorescence reduction circuit was applied which was
      integrated into as standard bench top flow cytometer to reduce this noise,
      thereby producing a 10-fold increase in detection sensitivity of the signal.
      Without the application of the autofluorescence reduction circuit, the positive
      control histogram distribution was virtually indistinguishable from the negative
      control sample distributions. After autofluorescence reduction, the data showed
      that the Y-chromosome DNA was only amplified in the Daudi cells subjected to the
      complete in situ PCR protocol. This increased sensitivity also provided direct
      detection of the Y-chromosome repeat sequence, albeit exhibiting less signal
      compared to the amplified target after the in situ PCR.

PMID- 8556958
TI  - Are there differences between laboratories that use or fail to use the CDC's
      guidelines to measure CD4+ and CD8+ T cells?

PMID- 8556959
TI  - Acquired resistance in dogs to repeated infestation with Ixodes scapularis
      (Acari: Ixodidae) reduces tick viability and reproductive success.
AB  - The purpose of this study was to determine whether dogs develop acquired
      resistance to adult Ixodes scapularis infestation in an experimental model. Five
      dogs were each infested with ten mating pairs of ticks every week for 7
      consecutive weeks, another five dogs were each infested with ten mating pairs
      once every 2 weeks for 10 weeks and four dogs served as controls not exposed to
      ticks. All ticks were allowed to feed to repletion and were collected only after
      dropping from the host. Several variables were measured to determine the extent
      of blood feeding success. Regression analysis indicated that the engorgement
      success, survival and mean tick engorgement weight declined with repeated
      infestation in both groups of dogs (p < 0.05). Tick oviposition as well as the F1
      viability declined with each successive infestation in both groups. These results
      suggest that repeated infestation with I. scapularis elicits a protective immune
      response against tick feeding and could serve as a limiting factor in the spread
      and transmission of Borrelia burgdorferi.

PMID- 8556960
TI  - Ixodid tick salivary gland extracts inhibit production of lipopolysaccharide
      induced mRNA of several different human cytokines.
AB  - Extracts prepared from the salivary glands (SGE) of partially fed adult female
      Rhipicephalus appendiculatus ticks reduced the expression by human peripheral
      blood leukocytes 9PBLs) of lipopolysaccharide (LPS)-stimulated cytokine mRNA.
      Treatment with SGE had no obvious effect on cytokine mRNA production when
      compared with untreated PBLs. LPS treatment induced or increased mRNA production
      for IFN alpha, TNF-alpha, IL-1 alpha, IL-1 beta, IL-5, IL-6, IL-7 and IL-8. All
      the LPS-stimulated cytokine mRNAs were reduced when treated with a mixture of LPS
      and SGE. The results indicate the potential of ticks in modulating the cytokine
      network of their vertebrate hosts, possibly to facilitate blood feeding.

PMID- 8556961
TI  - Cutaneous hypersensitivity induced in dogs and guinea-pigs by extracts of the
      tick Rhipicephalus sanguineus (Acari: Ixodidae).
AB  - The cutaneous hypersensitivity induced by Rhipicephalus sanguineus tick extract
      in dogs (natural host) and guinea-pigs (laboratory host) was evaluated. The left
      ear of infested and control (tick-bite naive) dogs and guinea-pigs was injected
      intradermally with an extract from unfed adult ticks and the right ear with
      phosphate buffered saline (PBS). Ear thickness variations were then measured
      after 10 min and 1, 2, 6, 18, 24, 48, 72 and 96 h post-injection. Results were
      expressed as percentual changes in the ear thickness in relation to pre
      inoculation values. The final variation in ear thickness induced by the extract
      was given by subtracting, in each animal, the right ear percentual increase from
      that of the left ear. Guinea-pigs were tested at two different times following
      infestation and with two different doses of extract. Infested guinea-pigs from
      the three experiments developed an immediate (within the first 2 h post
      inoculation) and a strong delayed reaction (24 h) to the extract. Dogs, unlike
      guinea-pigs, developed only a strong immediate reaction whereby an 80% increase
      in ear thickness was observed. Control animals, with the exception of one dog,
      did not develop any significant reaction to the extract. Only mild reactions were
      induced by PBS in the right ear of all animals. The correlation between the
      absence of a strong delayed type reaction to tick extract and the lack of
      resistance of the natural host to R. sanguineus tick is discussed.

PMID- 8556962
TI  - Diagnostic DNA amplification from individual tick eggs, larvae and nymphs.
AB  - The species of single tick eggs, larvae and nymphs was determined by PCR
      amplification and characterization of the hypervariable, second transcribed
      spacer (ITS2) of the multicopy ribosomal RNA gene (rDNA). Engorgement of larvae
      and nymphs did not preclude species identification. The method is generally
      applicable for ixodid and argasid ticks and can be used for epidemiological
      studies requiring the identification of individuals from pre-adult stages.

PMID- 8556963
TI  - Multiple sclerosis.
AB  - Multiple sclerosis is a chronic disease that begins in late adolescence or
      adulthood. It is highly variable in its expression and severity. It is believed
      to be autoimmune in nature. The cause is unknown; both genetic and environmental
      factors have been implicated in the pathogenesis. MS generally presents with the
      acute or subacute onset of neurologic abnormalities that may wax and wane over
      many years. Diagnosis is generally made by means of observation of the clinical
      course in conjunction with a neurologic examination and laboratory tests. These
      tests may include magnetic resonance imaging of the head and spine, lumbar
      puncture, and evoked potentials. Treatment is based on general supportive care,
      the use of corticosteroids for relapses, and symptomatic management of ongoing
      problems. The frequency of relapses can be reduced with interferon-beta
      (Betaseron). Copolymer 1 and interferon-beta la are being evaluated by the U.S.
      Food and Drug Administration for approval for use for reduction in the frequency
      of relapses in relapsing-remitting MS. Treatment of chronic progression is often
      attempted with immunosuppressive agents such as corticosteroids, azathioprine,
      and cyclophosphamide. Use of other agents is being investigated.

PMID- 8556964
TI  - Evaluating the reinforcement value of clinic-based privileges through a multiple
      choice procedure.
AB  - A novel multiple choice procedure was utilized to evaluate the potential
      reinforcement value of three clinic-based incentives available during routine
      methadone treatment: methadone take-homes, methadone dose increases, and extra
      counseling. Fourteen methadone maintenance patients who were not earning any of
      these incentives completed a multiple choice form in which they made choices
      between pairs of incentives and subsequently between each incentive and a series
      of monetary values. Choice behavior was intermittently reinforced by randomly
      awarding to patients one of their chosen preferences. Results demonstrated that
      take-homes were worth US$20.24 and were rated as more desirable than dose
      increases (US$13.89) and extra counseling (US$7.47). The study updates and
      extends past research in this area and provides a methodology for establishing
      both a monetary value for clinic-based incentives and an absolute magnitude
      between preferences. The procedure could be used to examine a larger number of
      potential reinforcers and to understand individual differences in responding to
      incentive-based treatment programs.

PMID- 8556965
TI  - Amantadine does not reduce cocaine use or craving in cocaine-dependent methadone
      maintenance patients.
AB  - We tested the efficacy of amantadine to reduce cocaine use or craving in cocaine
      dependent methadone maintained patients. Two doses of amantadine (200 mg p.o.
      daily, n = 16, and 200 mg p.o. bid, n = 21) were tested against placebo, n = 22,
      in a random assignment, double-blind clinical trial lasting nine weeks.
      Amantadine was well tolerated. However, neither dose of amantadine was more
      effective than placebo in reducing cocaine use and craving.

PMID- 8556966
TI  - No association between the c2 allele at the cytochrome P450IIE1 gene and alcohol
      induced liver disease, alcohol Korsakoff's syndrome or alcohol dependence
      syndrome.
AB  - Cytochrome P450IIE1 metabolises, and is induced by ethanol. The 5' regulatory
      sequence of the gene is polymorphic; that identified by the c2 allele has been
      shown by transfection studies to confer an increased rate of transcription. A
      recent report indicating an association between this allele and alcohol induced
      cirrhosis suggests that it may contribute to the genetic vulnerability to this
      disease. We have examined this polymorphism in patients of western European
      origin with alcohol induced cirrhosis, alcohol Korsakoff's syndrome and alcohol
      dependence syndrome. We were unable to detect any association between this allele
      and any of these diseases.

PMID- 8556967
TI  - Imipramine treatment of cocaine abuse: possible boundaries of efficacy.
AB  - A 12-week placebo-controlled, randomized clinical trial was undertaken to
      evaluate imipramine as a treatment for cocaine abuse, and to examine whether its
      effect may be limited to subgroups defined by route of use or by diagnosis of
      depression. One-hundred thirteen patients were randomized, stratified by route of
      use and depression. All patients received weekly individual counseling. Compared
      to placebo the imipramine group showed greater reductions in cocaine craving,
      cocaine euphoria, and depression, but the effect of imipramine on cocaine use was
      less clear. A favorable response, defined as at least 3 consecutive, urine
      confirmed, cocaine-free weeks was achieved by 19% (11/59) of patients on
      imipramine compared to 7% (4/54) on placebo (P < 0.09). The imipramine effect was
      greater among nasal users--33% (9/27) response on imipramine vs. 5% (1/22) on
      placebo (P < 0.02). Response was also more frequent, but not significantly so,
      among depressed users on imipramine (26%, 10/38) than on placebo (13%, 4/31) (P <
      0.19). Response rates were low in intravenous and freebase users and those
      without depression. Considered together with the literature on desipramine, these
      data suggest tricyclic antidepressants are not promising as a mainstay of
      treatment for unselected cocaine abusers. However, tricyclics may be useful for
      selected cocaine abusers with comorbid depression or intranasal use, or in
      conjunction with a more potent psychosocial intervention.

PMID- 8556968
TI  - Comorbidity between DSM-IV alcohol use disorders and major depression: results of
      a national survey.
AB  - The purpose of this study was to describe detailed patterns of comorbidity
      between Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition
      (DSM-IV) alcohol use disorders and major depression using a representative sample
      of the United States. Comorbidity rates and associations between DSM-IV alcohol
      use disorders and major depression were expressed as odds ratios with confidence
      intervals adjusted for the complex design characteristics of the NLAES.
      Comorbidity analyses were presented by sex, ethnicity and age for past year,
      prior to past year and lifetime diagnoses. Virtually all odds ratios were
      significantly greater than 1.0, demonstrating that comorbidity of alcohol use
      disorders and major depression is pervasive in the general population. The
      magnitude of the association remained stable across the three time frames but
      diagnostic and subgroup variations in comorbidity were noted. The association
      between alcohol dependence and major depression was greater than the association
      between abuse and major depression and the association between alcohol abuse and
      major depression was consistently greater for females and blacks, compared to
      their male and non-black counterparts. Implications of the results are discussed
      in terms of professional help seeking, the self-medication hypothesis, and
      differential social control theory.

PMID- 8556969
TI  - Craving and drug reward: a comparison of methadone and clonidine in detoxifying
      opiate addicts.
AB  - Based upon findings relating to the reinstatement of responding from the animal
      laboratory, the present study investigated whether methadone, a synthetic opiate,
      would prime the desire to use heroin for its pleasant effect (i.e. for positive
      reinforcement) compared to clonidine, a non-opiate drug, in detoxifying opiate
      addicts (n = 16). In-patient opiate addicts were tested at maximum withdrawal and
      minimal withdrawal, and self-reported desire to use heroin (i) for its pleasant
      effect (positive craving) and (ii) to alleviate an unpleasant feeling or mood
      (negative craving) was recorded before drug administration, immediately after
      drug administration and on 4 further occasions, 15 min apart. In addition, self
      reported rating of opiate withdrawal symptoms were also recorded. Although
      elevated in the methadone group, the difference between methadone and clonidine
      groups in positive craving did not reach statistical significance. Interpretation
      of the data is complicated by elevated baselines of positive craving in the
      methadone group at minimum withdrawal. Measures of negative craving and self
      reported withdrawal symptoms showed a similar pattern of decline, and were
      significantly correlated at maximum withdrawal, thereby providing evidence from
      substance misusers themselves that the constructs of positive and negative
      reinforcement can be differentiated.

PMID- 8556970
TI  - Carbamazepine and cocaine-cue reactivity.
AB  - Subjective and electroencephalographic reactions to cocaine cues were evaluated
      in 33 cocaine-dependent out-patients and 17 non-cocaine-dependent controls.
      Subjective, EEG, and autonomic reactions to three 5-min videos (cocaine
      associated, erotic, neutral) were evaluated twice with an interpolated 1-week
      interval. Between evaluations, cocaine-dependent patients received carbamazepine
      400 mg daily or matching placebo in double-blind fashion. In all three groups the
      cocaine-associated and erotic videos produced a comparable increase in the self
      rated desire for cocaine and reduction in total EG power. Carbamazepine treatment
      increased EEG fast alpha power and self-rated fatigue, and decreased self-rated
      concentration and vigor. However, it had no specific effect on subjective or
      physiological reactivity to either the cocaine-associated or erotic videos. This
      negative finding is consistent with recent clinical trials of carbamazepine for
      cocaine dependence.

PMID- 8556971
TI  - Acute subjective responses to paroxetine in normal volunteers.
AB  - The purpose of this study was to compare the subjective effects of the selective
      serotonin reuptake inhibitor, paroxetine, to those of the prototypic stimulant, d
      amphetamine. Ten healthy volunteers attended 5 sessions and received paroxetine
      (10, 20, 50 mg), d-amphetamine (20 mg), and placebo. Subjective effects were
      measured at regular intervals for 26-30 h. Paroxetine and d-amphetamine produced
      highly dissimilar effects on mood. For example, whereas d-amphetamine increased
      ratings of euphoria, drug high, and desire for drug, paroxetine produced no
      effects on these measures. Conversely, whereas paroxetine increased ratings of
      Confusion and Fatigue, d-amphetamine did not. These findings suggest that
      serotonin does not play a significant role in mediating the positive subjective
      effects of stimulant drugs.

PMID- 8556972
TI  - Levels and correlates of polydrug use among heroin users and regular amphetamine
      users.
AB  - Data from a sample of 329 primary heroin users and from a sample of 301 regular
      amphetamine users were analysed in order to determine the extent and correlates
      of polydrug use among illicit drug users. Both samples exhibited high levels of
      polydrug use, with means of 5.2 (heroin) and 6.3 (amphetamines) drug classes used
      in the preceding 6 months. Multi-variate analyses indicated that being younger,
      being male, not being in treatment, being an injector, having recently borrowed
      injecting equipment and being from the regular amphetamine using sample were
      independently associated with higher levels of polydrug use. Rather than
      increasing levels of polydrug use being associated with age, illicit drug users
      appear to reduce their range of drugs as they get older. The 'pure' heroin or
      amphetamine user was extremely rare. It is concluded that to characterise drug
      users as 'heroin' or 'amphetamine' users misses the context in which these drugs
      are used.

PMID- 8556973
TI  - Patterns of injecting and sharing in a Scottish prison.
AB  - Although the potential for prisons to act as the setting for HIV transmission has
      been recognised, there is an enduring lack of knowledge in this area. Data are
      presented on patterns of injecting and sharing in Edinburgh prison (Scotland),
      1993-1994. There was a relatively low level of injecting in Edinburgh prison
      during this period, with 13% (8/60) of a sample of drug users having injected at
      some point during their current sentence. The majority (6/8) of those who had
      injected had shared injecting equipment. Where sharing took place, the level of
      HIV risk was variable, but would have been higher had cleaning fluids not been
      available within the prison, or had they not been used by sharers. The
      implications of this study for drug service provision in prisons is discussed.

PMID- 8556974
TI  - Mazindol treatment for cocaine dependence.
AB  - This double-blind placebo-controlled treatment study tested the efficacy of
      mazindol in currently cocaine-dependent out-patients. Forty-three patients were
      randomized to mazindol (2 mg QD) vs. placebo treatment for 6 weeks. All patients
      received weekly group counseling. Patients improved with respect to objective
      (urine toxicology) and subjective (self-report of times used, dollars spent,
      craving, etc.) measures. There was no response difference between patients
      treated with mazindol and those who received placebo.

PMID- 8556975
TI  - The association between childhood irritability and liability to substance use in
      early adolescence: a 2-year follow-up study of boys at risk for substance abuse.
AB  - The aim of this investigation was to determine whether irritability, defined as
      the propensity to experience and express anger following actual or perceived
      provocation, is a component of the liability to alcohol and drug abuse. Sons of
      substance abusing fathers (n = 40) and normal fathers (n = 56) were studied when
      they were 10-12 years of age and followed-up 2 years later. Hierarchical
      regression analysis revealed that resting salivary cortisol concentration,
      impulsivity and family discord measured when the subjects were 10-12 years of age
      explained 35% of the variance on a scale measuring irritability 2 years later. At
      follow-up, when the boys were 12-14 years of age, it was observed that
      irritability scale scores and family discord were the only variables that
      accounted for significance variance on a scale measuring coping via alcohol and
      drug use. Latency and amplitude of the N1 and P3 event-related potentials of an
      auditory oddball task, measured at age 10-12, were not associated with drug use
      at age 12-14. These results indicate that family dysfunction, stress state of the
      child, and low behavioral self-control additively account for a significant
      proportion of variance on irritability scale scores 2 years later, and that this
      trait, in conjunction with family discord, is associated with substance use as a
      coping response by early adolescence.

PMID- 8556976
TI  - Allergy in otolaryngology--the experience of an expert.

PMID- 8556977
TI  - Traumatic dislocation of the incus.

PMID- 8556978
TI  - Recurrent vocal fold hemorrhage.

PMID- 8556980
TI  - Changing the nasal tip: Part I.

PMID- 8556979
TI  - Telescopic view of Woodruff's naso-nasopharyngeal plexus.

PMID- 8556981
TI  - Mandibular osteosynthesis with intraoral miniplates and cortical bone screws.
AB  - Previously, this author and others described a technique of maxillomandibular
      fixation utilizing intraoral cortical bone screws and intermaxillary wires. This
      procedure has been very successful in achieving superior fixation of relatively
      undisplaced fractures in a fraction of the time previously required for arch bar
      application. A method was sought to extend the procedure to include displaced
      mandibular fractures as well. Miniplates have been utilized through the same
      intraoral approach to provide reduction of displaced fragments. Excellent
      fixation has been achieved with anatomical reduction while utilizing less than
      half the previous operating time. It appears that the majority of mandibular
      fractures can be treated with this combination of techniques.

PMID- 8556982
TI  - Hemoptysis and pseudohemoptysis: the patient expectorating blood.
AB  - Patients expectorating blood seek evaluation and treatment from a variety of
      clinicians. Although the bleeding may arise either from the lungs (hemoptysis) or
      from the upper aerodigestive tract (pseudohemoptysis), the evaluation commonly
      focuses on exclusion of a pulmonary neoplastic source. Likewise, most literary
      reviews only focus on hemoptysis as it relates to pulmonary malignancies. The
      present retrospective review identifies 471 patients with the diagnosis of
      hemoptysis over a six-year period, and 10% were ultimately found to have UAT
      etiologies for their bleeding. UAT cancers were identified as the source in 2.1%
      of all patients, either due to primary lesions or via metastases. The majority of
      UAT cancers had been previously diagnosed prior to this episode of hemoptysis.
      This review indicates that a thorough UAT history and exam is warranted in the
      hemoptysis patient because of the significant occurrence of UAT causes. However,
      the likelihood of finding an occult UAT cancer in this patient population is very
      low with the only risk factor being a previous history of a UAT neoplasm.

PMID- 8556983
TI  - Rosai-Dorfman disease involving the nasal septum.
AB  - Rosai-Dorfman disease, or sinus histiocytosis with massive lymphadenopathy
      (SHML), is a benign, self-limited pseudolymphomatous entity with characteristic
      histologic features. The disease may be atypically present in the absence of
      detectable nodal involvement. This is a case of nasal septum involvement of Rosai
      Dorfman disease without clinically apparent lymphadenopathy.

PMID- 8556984
TI  - Outcome-oriented managed care comparing efficacies of cefaclor and amoxicillin in
      acute and recurrent acute otitis media.
AB  - A study utilizing outcome-oriented cure is employed to show the effectiveness of
      a given medical treatment. A specific patient population is studied in order to
      determine the most effective treatment for a common clinical disorder. A total of
      201 children were retrospectively studied to evaluate the efficacy and side
      effects of amoxicillin and cefaclor in the treatment of acute otitis media and
      recurrent acute otitis media. There were 456 episodes of acute otitis media; 245
      episodes were treated with amoxicillin with an efficacy of 91%, while 211
      episodes were treated with cefaclor with an efficacy of 97%. The dosage of 40
      mg/kg/day, divided in three equal doses, was employed for both antibiotics in the
      treatment of acute otitis media, while half of this amount was given once daily
      for the chemoprophylaxis of recurrent acute otitis media. In the 87 courses of
      chemoprophylaxis with cefaclor for recurrent otitis media, the efficacy was found
      to be 53%; while amoxicillin was found to be effective in 30% of the 33 patients
      studied. There were fewer side effects noted in the cefaclor group than in the
      amoxicillin group (4% vs. 12%). Both drugs caused diarrhea, while cefaclor also
      caused a mild maculopapular rash in two patients (1.67%). While amoxicillin
      remains the drug of choice for acute otitis media (AOM), this study suggests that
      cefaclor may be a better selection in the chemoprophylaxis of recurrent acute
      otitis media.

PMID- 8556985
TI  - Hemangiopericytoma of the skull base and Collet-Sicard syndrome: a case report.
AB  - Hemangiopericytoma (HP) is a mesenchymal tumor that originates from the pericytes
      of the capillary walls. This is a rare neoplasm, particularly in the head and
      neck; the skull base is involved exceptionally. We report a case of a large HP
      located in the jugular foramen. The last four cranial nerves were involved,
      causing a Collet-Sicard syndrome associated with facial palsy. Only one case of
      HP and Collet-Sicard syndrome is reported in the literature. The clinical course
      of the disease is described, emphasizing the long period of elapsed time between
      onset of the complaints and the final diagnosis. Diagnostic procedures and
      immunohistochemical evaluation are analyzed, along with the possible differential
      diagnosis with other pathological processes that more frequently involve the
      jugular foramen.

PMID- 8556986
TI  - Effect of cotton, hemp, and flax dust extracts on lung permeability in the guinea
      pig.
AB  - Byssinosis is an occupational lung disease in textile mill workers exposed to the
      respirable dusts of cotton, hemp, and flax. This study investigated the influence
      of aqueous extracts from these dusts on overall lung permeability in the guinea
      pig as an index of respiratory epithelial damage. Lung permeability was assessed
      by absorption into blood from the lung of inhaled technetium-99m
      diethylenetriamine penta-acetate (Tc-DTPA) using gamma-scintigraphy. The half
      life for Tc-DTPA absorption (t1/2) was significantly reduced following a 4-week
      inhalation treatment with cotton, hemp, or flax dust extracts when compared to
      saline control. There was at least a partial return to normal permeability 7 days
      after stopping treatment. A single inhalation of extract did not affect the t1/2,
      but increased the number of neutrophils in bronchoalveolar lavage fluid 24 h
      postexposure. Neutrophil migration into the airspaces therefore appeared to
      precede the increased lung permeability. Long-term exposure was not associated
      with respiratory epithelial shedding, suggesting that the increased permeability
      reflects a loss of epithelial tight junction integrity arising from repeated
      exposure to as yet undefined agents in these dusts.

PMID- 8556987
TI  - Clearance in smaller airways of inhaled 6-microm particles in subjects with
      immotile-cilia syndrome.
AB  - In subjects with an inherited lack of mucociliary transport, so called immotile
      cilia syndrome (ICS), coughing effectively clears particles deposited in larger
      airways of the tracheobronchial region. The present study investigated clearance
      in smaller airways of 111In-labeled 6-microm (aerodynamic diameter) monodisperse
      Teflon particles in six subjects with ICS. The particles were inhaled at an
      extremely slow flow, 0.05 L/s. Theoretical calculations and experimental data in
      healthy subjects using this slow flow support particle deposition mainly in
      smaller ciliated airways, i.e., in bronchioli (generations 12-16). This contrasts
      with the more centrally deposited pattern obtained using a normal inhalation
      flow, 0.5 L/s. Lung retention was measured at 0, 24, 48,72 and 96 h. Clearance
      was significant every 24 h measured over the first 72 h, whereupon it slowed
      down. The fractions of retained particles were significantly (p < .01) larger
      than those found for healthy subjects using the slow inhalation flow and those
      found for ICS subjects using a normal inhalation flow. The results indicate that
      clearance of particles in smaller airways is incomplete and that cough cannot
      fully compensate for the lack of mucociliary transport in this region.

PMID- 8556989
TI  - Patterns of particle deposition and retention after instillation to mouse lung
      during acute injury and fibrotic repair.
AB  - Studies on particle deposition, clearance, and translocation to the interstitium
      and lymph nodes have mostly been carried out on normal animals. This study
      evaluates changes in these parameters after inert particles are deposited in
      lungs during acute inflammatory injury and during fibrotic repair. Three days
      after instilling bleomycin to mouse lungs, there is an inflammatory response and
      necrosis of type 1 epithelium. When carbon is instilled in these lungs, particles
      appear uniformly distributed, some are engulfed by the increased phagocytes, but
      many particles cross the denuded epithelial surface to reach interstitial
      macrophages. Subsequently much carbon remains in the connective tissue and some
      reaches hilar lymph nodes. After 16 weeks, particle retention in the lung is
      significantly greater than in a carbon-only control group. Other mice received
      carbon 4 weeks after bleomycin when epithelial repair had occurred and many areas
      of the lung were fibrotic. Very little carbon reached these regions; most was
      deposited in less fibrotic areas of lung. Few particles crossed the epithelium so
      that retained carbon in lung and lymph nodes was equivalent to that in the carbon
      only group. The results show that a fibrotic lung structure alters the patterns
      of particle deposition in the lung. However, the major factor determining
      enhanced particle retention is the integrity of the epithelium. Particle
      deposition at a time of epithelial injury is associated with enhanced
      translocation to interstitium and lymph nodes. This may result in pathologic
      changes if a normally nonreactive low dose of toxic particles is deposited when
      the epithelium is breached.

PMID- 8556988
TI  - Regulation of airway cholinergic neurotransmission by Ca(2+)-activated K+ channel
      and Na(+)-K+ adenosinetriphosphatase.
AB  - Stimulation of Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase may play an
      important role in the relaxant responses of airway smooth muscle to certain
      bronchodilators. To test whether cholinergic neuroeffector transmission can be
      modulated by Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase, canine airway
      smooth muscle was studied under isometric conditions in vitro. Addition of
      charybdotoxin (10(-7) M) did not alter the contractile responses to acetylcholine
      but augmented electrical field stimulation-induced contractions at 1-10 Hz (p <
      .01), whereas apamin and glibenclamide were without effect. This effect of
      charybdotoxin was dose dependent, with the maximal increase being 36.8 +/- 5.3%
      (p < .001). Ouabain (10(-7) M) increased contractions induced by both electrical
      field stimulation and acetylcholine. The magnitude of the increase in contractile
      responses to electrical field stimulation was similar to that of acetylcholine at
      an ouabain concentration of up to 3 x 10(-7) M, but the former was significantly
      greater at 10(-6) M ouabain (p < .05). These results suggest that both Ca(2+)
      activated K+ channel and Na(+)-K(+)-ATPase may be operative in the regulation of
      cholinergic neurotransmission by inhibiting the exocytotic release of
      acetylcholine from the vagal nerve terminals.

PMID- 8556990
TI  - Lung lesions in experimental hydrostatic pulmonary edema: an electron microscopic
      and morphometric study.
AB  - Distinct barrier lesions and an apical-basal distribution of alveolar edema fluid
      in either moderate or high elevated pressure edema lungs have been found in
      previous studies. In the present study, quantitative measurements were obtained
      by using electron microscopy and morphometry of extravascular lung water and
      barrier lesions, on the relations between interstitial and alveolar edema fluid
      as well as between extravascular lung water and barrier lesions. The study
      further addressed the question of whether 6% bovine serum albumin (BSA) perfusion
      could induce lung ultrastructure alterations. It was found that interstitial
      fluid distribution is similar to that of alveolar edema fluid. Epithelial blebs
      are also distributed with an apical-basal gradient, and are always submerged in
      alveolar edema fluid. Perfusion with 6% bovine serum albumin does not induce any
      lung ultrastructure alterations. The results indicate that endothelium and
      epithelium play a different role in controlling fluid movement between capillary
      and extravascular spaces and thus in preventing the formation of interstitial and
      alveolar edema. Because the interaction of cells and tissue must be taken into
      account, simple physiological models of pulmonary fluid exchange may not be
      adequate to explain pulmonary edema formation.

PMID- 8556991
TI  - Nitric oxide synthesis by rat pleural mesothelial cells: induction by growth
      factors and lipopolysaccharide.
AB  - The purpose of this study was to determine if certain growth factors and
      bacterial products induce pleural mesothelial cells (PMC) to produce nitric oxide
      (NO). Confluent monolayers of rat PMC were exposed to epidermal growth factor
      (EGF), platelet-derived growth factor (PDGF), or lipopolysaccharide (LPS)
      individually and in various combinations for 24-72 h. Concentrations of nitrite
      and nitrate were quantified and used as an indirect measure of NO production. LPS
      stimulation resulted in a significant increase in nitrite/nitrate concentration,
      but neither EGF nor PDGF alone or combined had any significant effect relative to
      control. However, LPS combined with either EGF or PDGF caused a significant
      increase in nitrite/nitrate concentration relative to LPS alone and growth factor
      alone. The highest level level of nitrite/nitrate concentration was observed with
      the triple combination of LPS, EGF, and PDGF. Nitrite/nitrate accumulation was
      significantly increased at 24 h by all combinations, and continued to increase,
      with the highest concentration observed after 72 h of exposure. Nitrite/nitrate
      production was significantly inhibited by NG-nitro-L-arginine methyl ester and
      this inhibition was reversed by the addition of L-arginine, suggesting that
      nitrite and nitrate were derived from the L-arginine-dependent formation of NO.
      These data indicate that PMC can be induced to produce relatively large amounts
      of NO in response to growth factors combined with LPS.

PMID- 8556992
TI  - Murine pulmonary Ca(2+)-transport system activated by allergic immune response
      retains sensitivity to oxidative stress.
AB  - Exaggerated oxygen radical production by airway cells may contribute to increased
      airway responsiveness and heightened smooth muscle constriction in asthmatic
      lungs. Smooth muscle cell contractility in the lung is regulated by Ca2+
      homeostasis. The contribution of inflammatory cells to these events is unclear. A
      murine model of allergic pulmonary hypersensitivity was developed to study the
      role of Ca2+ transport in allergic pulmonary reactions. Sensitization of mice was
      accomplished by injection with ovalbumin (OA) (1 or 50 micrograms) or OA (1
      microgram) plus Al(OH)3. Pulmonary responses were elicited by inhalation
      provocation challenge with OA aerosol and quantified by the extent of
      inflammatory cell infiltrate at 24 h. Increased Ca2+ transport was found in
      microsomes and homogenates of the lung after antigen challenge. Activation of
      Ca2+ transport was correlated with the severity of the allergic pulmonary
      response as evidenced from specific antibody production and inflammatory cell
      infiltrate. The greatest increase in Ca2+ transport was noted in microsomes from
      mice sensitized with OA plus adjuvant. Ca2+ transport in sensitized, but not in
      control mice, was responsive to oxidative stress induced by addition of phenol
      and hydrogen peroxide. Lung homogenates from both groups of animals responded
      similarly to phenoxyl radical-induced oxidative stress induced by phenol plus
      exogenous tyrosinase. These results are the first to indicate heightened Ca2+
      transport in pulmonary microsomes following an allergic lung response and
      emphasize the role of aluminum hydroxide in enhancing allergic reactions in the
      lung. The responsiveness of the system to oxidative stress suggests that
      oxidative mechanisms may contribute to the physiologic and pathologic
      manifestations, such as airway hyperreactivity, associated with allergic
      pulmonary disease.

PMID- 8556993
TI  - Modification of alveolar macrophage function with bis-basic ethers of fluorene
      and fluoren-9-substituted derivatives.
AB  - Bis-basic ethers of fluorene and fluoren-9-substituted derivatives such as
      tilorone have been reported to inhibit silica-induced fibrosis in rats. The
      potential antifibrotic potency of 2,7-bis(diethylamino)ethoxy fluorene (F-9-H,H),
      fluorenone (F-9-one), fluorenoxime (F-9-oxime), and fluorenol (F-9-ol) was F-9
      oxime > F-9-one approximately F-9-H,H >> F-9-ol. Since the release of reactive
      oxygen species and growth factors from alveolar macrophages (AM) in response to
      silica exposure has been linked to the development of pulmonary fibrosis, the
      present study was carried out to determine the inhibitory effects of these
      compounds on rat AM activity in vitro. The following parameters were monitored:
      (1) cellular viability; (2) zymosan-induced respiratory burst activity
      (superoxide and hydrogen peroxide release, chemiluminescence, and oxygen
      consumption) of AM; (3) drug binding to AM; and (4) lipopolysaccharide (LPS)
      stimulated interleukin-1 (IL-1) release from AM. The bis-basic ethers, at 40
      microM, did not affect cell viability when incubated with AM for 30 min, but
      significantly inhibited zymosan-induced macrophage respiratory burst activity.
      The inhibitory effect of these agents was F-9-oxime > F-9-one approximately F-9
      H,H >> F-9-ol. Binding of these drugs to AM was time and dose dependent, and
      exhibited the following binding affinity: F-9-oxime > F-9-one > F-9-H,H > F-9-ol.
      F-9-oxime was shown to inhibit LPS-stimulated IL-1 release by AM in a dose
      dependent manner. This inhibition of IL-1 release by AM cannot be explained as a
      decrease in viability. In addition, these drugs were also shown to impair human
      fibroblast proliferation in response to serum stimuli without impairing cell
      viability. These results indicate a positive correlation between drug binding to
      AM or other cell types and their inhibitory effects on cellular activities
      including oxygen consumption, superoxide release, hydrogen peroxide secretion,
      chemiluminescence, IL-1 release, and proliferation. The ability of these bis
      basic ethers to modify AM and fibroblast functions in vitro suggests that further
      investigation of their reported antifibrotic potency in vivo is warranted.

PMID- 8556994
TI  - Molecular mechanisms of antifibrotic effect of interferon gamma in bleomycin
      mouse model of lung fibrosis: downregulation of TGF-beta and procollagen I and
      III gene expression.
AB  - The present study was undertaken to elucidate the mechanism for the antifibrotic
      effect of interferon gamma (IFN-gamma) in the bleomycin (BL)-mouse model of lung
      fibrosis. The expression of transforming growth factor (TGF-beta) and procollagen
      I and III and their mRNAs was investigated in the BL-mouse model of lung fibrosis
      with and without IFN-gamma treatment by Northern and slot blot analyses. Temporal
      changes in the content of procollagen and TGF-beta mRNAs in the lungs of mice
      receiving saline or BL by intratracheal route, with and without IFN-gamma
      treatment by intramuscular route, were quantitated. The level of TGF-beta mRNA
      increased rapidly and peaked at day 5, whereas the levels of mRNAs for
      procollagens alpha 1(I) and alpha 1(III) peaked at 10 days after BL instillation.
      The peak levels of these mRNAs in BL-treated animals were five- to sevenfold
      higher than those of the control. The increase in TGF-beta mRNA in the lungs of
      BL-treated mice preceded the increase in the synthesis of type I and type III
      procollagen mRNAs. BL treatment also increased the hydroxyproline content
      significantly from 3 to 14 days as compared to the corresponding saline control
      groups. A maximal increase to 447 micrograms/lung from 223 micrograms/lung in
      saline control was obtained at 10 days after instillation. Daily treatment with
      IFN-gamma markedly reduced the BL-induced increases in the mRNA levels of TGF
      beta, and procollagen alpha 1(I) and alpha 1(III) without any effect on the lung
      level of beta-actin mRNA. IFN-gamma treatment also caused significant reduction
      in the BL-induced increase in the lung hydroxyproline content from 417 to 283
      micrograms/lung at 7 days and from 447 to 264 micrograms/lung at 10 days. It may
      be concluded from the findings of the present study that the cellular mechanisms
      for the antifibrotic effect of IFN-gamma in the BL-mouse model of lung fibrosis
      are to initially downregulate the BL-induced overexpression of TGF-beta mRNA, and
      subsequently procollagen mRNAs, leading to a decreased collagen content.

PMID- 8556995
TI  - Clinical Experiences with Esmeron. Luxembourg, 27-29 January 1995. Proceedings of
      an international meeting.

PMID- 8556996
TI  - Rocuronium bromide: time-course of action in underweight, normal weight,
      overweight and obese patients.
AB  - The duration of action and recovery of 0.6 mg kg-1 rocuronium in underweight,
      normal weight, overweight and obese patients were investigated. Forty-eight
      patients were divided into four groups, according to their body mass index, and
      were given 0.6 mg kg-1 rocuronium. The onset time, the duration 25% and either
      the spontaneous or induced recovery were measured according to the random
      assignment. The onset time in the obese group was shorter 60 (50-90) s compared
      to the other groups (underweight: 95 (40-320) s, normal: 95 (50-200) s,
      overweight: 90 (50-260) s, but the difference did not reach the level of
      statistical significance. The duration 25% was slightly prolonged in the obese
      patients (31.5 (21.0-61.0) min) when compared to the underweight (25.0 (15.0
      37.0) min), normal weight (26.0 (20.0-36.0) min) and overweight (27.0 (19.0-35.0)
      min) patients. No differences were observed in spontaneous (9.5-12.5 min) and
      induced (2.5-3.5 min) recovery.

PMID- 8556997
TI  - Priming studies with rocuronium and vecuronium.
AB  - We studied the effects of rocuronium and vecuronium as priming agents before both
      vecuronium and rocuronium neuromuscular blockade. Rocuronium is ineffective at
      priming rocuronium. Vecuronium is effective at priming rocuronium, producing an
      approximate 33% reduction in onset time. Rocuronium and vecuronium, when given as
      priming agents, both reduce the onset time of vecuronium block.

PMID- 8556998
TI  - Rocuronium with alfentanil and propofol allows intubation within 45 seconds.
AB  - Following induction with alfentanil (20 micrograms kg-1) and propofol (2.0-2.5 mg
      kg-1), four groups of patients were given rocuronium to determine conditions for
      rapid sequence intubation. Two groups received 0.9 mg kg-1 and two groups
      received 0.6 mg kg-1. In one of each dose groups, intubation was attempted after
      45 s and in the other after 60 s. Intubating conditions were scored on a four
      point scale but all were rated as excellent or good. Almost all intubating
      conditions were excellent in the 0.9 mg kg-1 groups.

PMID- 8556999
TI  - The effect of dose and the rate of stimulation on the action of rocuronium.
AB  - We studied the effect of administering multiples of the ED90 dose of rocuronium
      on the onset, duration and recovery index of neuromuscular block. The effect on
      onset time differed from that reported using train-of-four stimulation. This led
      us to investigate the effect of increasing the rate of ulnar nerve stimulation 10
      fold. This resulted in an approximately 50% reduction in the time to complete
      block.

PMID- 8557000
TI  - Dose-response and time-course of effect of rocuronium bromide in paediatric
      patients.
AB  - We determined dose-response curves and spontaneous recovery of neuromuscular
      function following a single ED95 dose of rocuronium in 10 infants (1-11 months
      old), 20 children (2-12 years old) and 20 adults (20-40 years old) during nitrous
      oxide-oxygen-thiopentone-alfentanil anaesthesia. Neuromuscular block was recorded
      as adductor pollicis EMG following a supramaximal train-of-four ulnar nerve
      stimuli at 10 s intervals. ED95 values were significantly less for infants than
      for children or adults (255 +/- 62, 402 +/- 68 and 350 +/- 78 micrograms kg-1,
      respectively, P = 0.0001). Time-course of recovery from an average 94%
      neuromuscular block was similar in all age groups with a 25-75% recovery time of
      6.5 +/- 1.8, 5.7 +/- 1.8 and 6.7 +/- 1.6 min in infants, children and adults,
      respectively. Thus, rocuronium is an intermediate-acting muscle relaxant in all
      age groups.

PMID- 8557001
TI  - Dose-response and time-course of action of rocuronium bromide.
AB  - Rocuronium is a new aminosteroidal muscle relaxant, the main feature of which is
      a low potency compared to other aminosteroidal muscle relaxants. The ED95 is
      approximately 0.3 mg kg-1, although the estimated potency may vary slightly with
      different modes of stimulation and under different anaesthetic techniques. The
      low potency is associated with a rapid onset of effect, a 2-3 x ED95 dose
      producing the maximum effect in 1-2 min. The duration of action is, however,
      comparable to other intermediate drugs such as atracurium and vecuronium. The
      estimated potency is similar in adults and the elderly, although the ED95 may be
      slightly higher in children. Rocuronium is affected in the same way as vecuronium
      by the use of volatile anaesthetic agents.

PMID- 8557002
TI  - Rocuronium- and mivacurium-induced neuromuscular block and intubating conditions:
      a comparison with vecuronium.
AB  - The time-course of action after an initial 2 x ED90 dose and after maintenance
      doses of 0.5 x ED90, and intubating conditions at 90 s after a 2 x ED90 dose
      following rocuronium, vecuronium and mivacurium were evaluated in anaesthetized
      adult patients. Neuromuscular measurements were performed with mechanomyography.
      Rocuronium produced a significantly deeper neuromuscular block at 90 s (mean and
      (standard deviation)) (91 (11%), compared to vecuronium (61 (22%)%) and
      mivacurium (58 (23)%). The onset time following rocuronium (172 (71)s) was
      significantly shorter than that following mivacurium (229 (60)s). At 90 s,
      intubating conditions were significantly better in the rocuronium group than in
      the vecuronium or mivacurium group. Mivacurium offered a significantly faster
      recovery of neuromuscular block following the 2 x ED90 dose and following an
      average of 45 min of clinical muscle relaxation (single twitch response < or =
      25%) compared to rocuronium and vecuronium: clinical duration 13 (4), 28 (9) and
      33 (9) min, respectively, and recovery time from 25 to 75% recovery of the single
      twitch response: 6 (2), 11 (4) and 14 (7) min, respectively.

PMID- 8557003
TI  - Onset time and evaluation of intubating conditions: rocuronium in perspective.
AB  - The customary methods for assessment of intubating conditions, namely the onset
      time in the adductor pollicis muscle and qualitative rating scales of the
      conditions at intubation, are unsatisfactory. The onset time of neuromuscular
      block in the adductor pollicis is not a meaningful, quantifiable endpoint,
      defining optimal intubating conditions. Consequently, its meticulous recording in
      all studies is probably obsolete. Qualitative rating scales are very subjective
      and a single standardized qualitative rating scale for the assessment of
      intubating conditions is required in order to improve the comparability of data
      from various studies. Clinical studies simulating rapid sequence induction in
      elective patients indicate that rocuronium 0.9 mg kg-1 may be suitable for crash
      intubation. This, however, needs to be confirmed in emergency cases.

PMID- 8557004
TI  - The pharmacokinetics of rocuronium bromide in hepatic cirrhosis.
AB  - The pharmacokinetics of aminosteroid neuromuscular blocking drugs have been shown
      to be altered in patients with hepatic cirrhosis. A reduced clearance and
      prolonged elimination half-life of pancuronium and vecuronium have been
      demonstrated. Pharmacokinetic studies of the newest aminosteroid neuromuscular
      blocking agent, rocuronium, performed in a small number of cirrhotic patients,
      have proved inconclusive, apart from noting a higher central volume of
      distribution than in healthy patients. This difference may result in a slightly
      delayed onset of neuromuscular block. Nevertheless, rocuronium, even in cirrhotic
      patients, has the fastest onset of action of any non-depolarizing neuromuscular
      blocking agent. Further pharmacokinetic studies are necessary of this drug in
      hepatic cirrhosis.

PMID- 8557005
TI  - Pharmacokinetics of rocuronium bromide in patients with and without renal
      failure.
AB  - We studied the onset and duration of action and pharmacokinetics of rocuronium
      bromide during anaesthesia with nitrous oxide, fentanyl and isoflurane after a
      single bolus dose of rocuronium (0.6 mg kg-1) in nine patients with chronic renal
      failure requiring regular haemodialysis, and in nine healthy control patients.
      Blood samples were collected over 390 min and concentrations of rocuronium and
      its putative metabolites measured using HPLC. Onset time for maximum block and
      duration of clinical relaxation (DUR25) were 61 (SD 25.0) s and 65 (16.4) s, 55
      (26.9) min and 42 (9.3) min, respectively, for patients with and without renal
      failure. The time for train-of-four ratio to return spontaneously to 0.7 was 99
      (41.1) min and 73 (24.2) min, respectively, in the two groups. None of these
      differences was significant. The pharmacokinetic data were best described by a
      three-exponential equation. There were significant differences between patients
      with and without renal failure in the rates of clearance (2.5 (1.1) mL kg-1 min-1
      and 3.7 (1.4) mL kg-1 min-1, respectively) and the mean residence times (97.1
      (48.7) min and 58.3 (9.6) min) (P < 0.05). The differences in other kinetic
      parameters were not significant.

PMID- 8557006
TI  - Structure-pharmacodynamic-pharmacokinetic relationships of steroidal
      neuromuscular blocking agents.
AB  - Several new steroidal non-depolarizing muscle relaxants have been synthesized and
      tested in humans recently. Results from these studies suggest that the
      differences in time-course of action between these compounds are mainly, if not
      totally, related to differences in biodisposition. Biodisposition, in turn, is
      determined largely by the physico-chemical characteristics of the drug, such as
      degree of lipophilicity and protein binding. The various pharmacodynamic and
      pharmacokinetic variables of a series of structurally related steroidal
      relaxants, varying in the ester substituent at the 17th position of the
      androstane skeleton, have been related to the degree of lipophilicity.
      Significant positive relationships could be shown between lipophilicity (logP at
      pH 7.4) and, among other things, potency (ED90), effective concentration (EC50),
      unbound plasma clearance (CLupl) and rate constant of transport between plasma
      and biophase (ke0). The aforementioned relationships between lipophilicity and
      pharmacokinetic variables resulted in significant inverse relationships between
      lipophilicity and time course parameters, such as onset time and duration of
      neuromuscular blocking effects. It is concluded that changes in the molecular
      structure of steroidal relaxants which enhance lipophilicity coincide with a
      decrease of (intrinsic) potency and a shorter time course of action. Protein
      binding appears to be of minor importance for the biodisposition and time course
      characteristics, since there were only small differences in degree of protein
      binding between most of the investigated compounds. However, the surprisingly
      fast initial rate of block development observed with rocuronium may in part
      result from its relatively high unbound fraction in plasma.

PMID- 8557007
TI  - Research and development of aminosteroid neuromuscular blocking agents: past and
      future.
AB  - This article attempts to summarize more than 25 years of chemistry and
      pharmacology research aimed at the search for clinically useful muscle relaxants
      based on an amino-androstane skeleton. This research strategy has produced three
      clinically useful drugs (pancuronium, vecuronium and rocuronium), and in addition
      has demonstrated that it is indeed possible to design a non-depolarizing
      neuromuscular blocker with the onset/offset characteristics of suxamethonium.
      Lastly, much has been learned about the variable clinical predictiveness of data
      obtained in various animal species with these compounds. This factor is probably
      mainly responsible for the difficulties and delay in producing the non
      depolarizing suxamethonium equivalent.

PMID- 8557008
TI  - Cross-reactivity of rocuronium with other neuromuscular blocking agents.
AB  - The cross-reactivity of rocuronium with other neuromuscular blocking agents
      (NMBAs) was studied in 31 patients known to be allergic to a muscle relaxant.
      Tests for diagnosing cross-reactivity were skin tests (prick tests and
      intradermal tests: IDTs), detection by RAST assay of IgEs against the quaternary
      ammonium group (QAS-RIA: quaternary ammonium sepharose radio-immuno-assay), QAS
      RIA inhibition test to detect IgE specificity, and leucocyte histamine release
      test (LHRT). Skin tests were performed with rocuronium, suxamethonium, gallamine,
      vecuronium, pancuronium, atracurium. The threshold for cross-reactivity was 10(
      1) with all the NMBAs except for atracurium (10(-2)). The inhibition test and
      LHRT were performed with rocuronium and the NMBA responsible for the shock. Ten
      volunteers made up the control group for prick tests, QAS-RIA, LHRT. Cross
      reactivity was found in 30 patients out of 31. Rocuronium did not cross-react in
      10 patients out of 31. They had negative cutaneous tests and negative LHRTs. In
      one of the five patients allergic to all the NMBAs available, rocuronium was the
      only one which did not cross-react. In those 10 patients, rocuronium may be
      safely used for subsequent anaesthesia. In terms of allergy, rocuronium appeared
      to be very close to the other steroidal NMBAs.

PMID- 8557009
TI  - Evaluation of neuromuscular effects and antagonism of rocuronium bromide: a
      preliminary report.
AB  - Twenty ASA I-II patients received either 2 or 3 x ED95 doses of rocuronium
      bromide during nitrous oxide, oxygen, propofol, fentanyl-based anaesthesia. The
      mean times to maximum block were 98 s and 74 s and the mean duration of clinical
      relaxation (recovery to 25% T1) was 35 min and 46 min following 620 micrograms kg
      1 and 930 micrograms kg-1, respectively. Neuromuscular blockade was antagonized
      with either neostigmine or edrophonium from a twitch height of 25%. Although
      there was no significant difference between the recovery times neostigmine
      appeared to give more consistent antagonism of rocuronium-induced blockade.

PMID- 8557010
TI  - Time-course of action and intubating conditions with rocuronium bromide under
      propofol-alfentanil anaesthesia.
AB  - Thirty ASA I and II patients received either an intubating dose of 0.6 mg kg-1
      rocuronium (2 x ED95, group 1) or 0.06 mg kg-1 as a priming dose followed by an
      intubating dose of 0.24 mg kg-1 rocuronium (group 2) 4 min later. Anaesthesia was
      induced with propofol (2.0 mg kg-1) and alfentanil (0.02 mg kg-1) and maintained
      with nitrous oxide/oxygen and propofol (6.0 mg kg-1 h-1). Neuromuscular function
      was monitored mechanomyographically and electromyographically with train-of-four
      (TOF) stimulation at the wrist every 10 s. The following parameters were measured
      and compared between the two groups: time to 90% block (intubation time), time to
      maximum block (onset time), and the times for T1 (25%, 75% and 90%) and TOF >
      70%. In group 1 the intubation time was significantly shorter (40 +/- 10 s) than
      in group 2 (51 +/- 11 s). Intubating conditions were good or excellent in both
      groups. The clinical duration of action was 28 +/- 8 min in group 1 and 15 +/- 3
      min in group 2, respectively. Mechanomyography showed a significantly faster
      development of neuromuscular block than electromyography. The comparison of
      mechanomyographically and electromyographically measured recovery times did not
      show any differences. In 60% of the patients a priming dose of 0.06 mg kg-1 was
      followed by a considerable decrease in neuromuscular function.

PMID- 8557012
TI  - Rocuronium bromide in the ICU: dose finding and pharmacokinetics.
AB  - Thirty patients requiring elective ventilation in the ICU received either
      intermittent boluses (25 patients) or a continuous infusion (five patients) of
      rocuronium. Degree of block was monitored by train-of-four stimuli and maintained
      at one twitch either observed or palpated. All patients were sedated with
      intermittent doses or an infusion of 0.14-0.4 microgram kg-1 h-1 of midazolam and
      received a continuous infusion of either sufentanil or fentanyl (0.25-2.0
      micrograms kg-1 h-1). Control of ventilation was better with the continuous
      infusion of rocuronium, but these patients also had a more intense block
      receiving 9.9 +/- 1.3 micrograms kg-1 min-1 as compared to 6.4 +/- 2.3 micrograms
      kg-1 min-1 in the bolus group. Elimination half-time, volume of distribution at
      steady-state, and mean residence time were significantly greater than in surgical
      patients receiving comparable infusions, but plasma clearance was similar.

PMID- 8557011
TI  - Dose-response, time-course of action and recovery of rocuronium bromide in
      children during halothane anaesthesia.
AB  - Two groups of children, aged 1-4 years (n = 28) and 5-10 years (n = 28),
      respectively, received at random one of four doses of rocuronium (0.12, 0.17,
      0.22 or 0.27 mg kg-1). When maximum block was obtained, further rocuronium to a
      total dose of 0.5 mg kg-1 was given. At a spontaneous T1 recovery of 25% the
      block was reversed with atropine and neostigmine in half the patients. The
      remainder were allowed to recover spontaneously. There was no difference in
      potency in the two age groups. An ED50 of 0.2 mg kg-1 was estimated. The
      estimates of ED50 were model-dependent of approximately 0.32 mg kg-1. The maximum
      block was found significantly higher in the younger age group (99.0 +/- 1.5%
      (mean +/- SD)) as compared to the older group (97.5 +/- 2.3%), and the clinical
      duration was also longer (16.6 +/- 5.3 min vs. 13.3 +/- 3.8 min), respectively.
      There was no significant difference between the two age groups in duration90
      (26.9 +/- 6.5 min, 22.5 +/- 6.7 min, respectively) and duration0.7 (27.6 +/- 6.0
      min, 24.9 +/- 7.9 min, respectively). Recovery time25-75, recovery time25-90, but
      not recovery time25-0.7 were found significantly longer in the 1-4 year group as
      compared to the times in older children. Neostigmine administration reduced
      recovery time by approximately half to two-thirds. MAP was not influenced by
      rocuronium. Following the injection of rocuronium in the younger age group there
      was a 15% increase in heart rate compared to a 10% increase in the age group 5-10
      years.

PMID- 8557013
TI  - Intubation conditions and time-course of action of low-dose rocuronium bromide in
      day-case dental surgery.
AB  - A relatively small dose of rocuronium (0.45 mg kg-1) was compared with equipotent
      doses of atracurium (0.35 mg kg-1) and vecuronium (0.075 mg kg-1) for ease of
      intubation at 60 s. All patients could be intubated but the proportion with
      excellent or good conditions was much greater with rocuronium. Mean clinical
      duration of effect of this dose was 22.2 min. There was no correlation between
      intubating conditions and the degree of block of the adductor policis.

PMID- 8557014
TI  - 1 x ED90 dose of rocuronium bromide: tracheal intubation conditions and time
      course of action.
AB  - The intubation conditions and time-course of action of a 0.3 mg kg-1 bolus of
      rocuronium were studied under alfentanil/propofol and
      fentanyl/thiopentone/enflurane anaesthesia. Forty healthy patients were randomly
      allocated to induction of anaesthesia with either alfentanil 20 micrograms kg-1
      and propofol 2.0-2.5 mg kg-1, or fentanyl 3 micrograms kg-1 and thiopentone 4-6
      mg kg-1. Approximately 5 min later, after calibration of mechanomyography, an
      i.v. bolus of 0.3 mg kg-1 rocuronium was administered. Laryngoscopy and tracheal
      intubation were attempted when maximum block occurred. Intubation was completed
      successfully in 39 patients. The passage of the tube was rated good or excellent
      in 18/20 (alfentanil/propofol group) and 18/19 patients in the other group. The
      times of onset were 65 s and 69 s, respectively. It is concluded that a 1 x ED90
      dose of rocuronium will rapidly provide good or excellent intubation conditions
      in the majority of cases.

PMID- 8557015
TI  - Hypothermic cardiopulmonary bypass influences the concentration-response
      relationship and the biodisposition of rocuronium.
AB  - In 10 patients scheduled for elective coronary artery bypass grafting under
      midazolam-sufentanil anaesthesia, the influence of hypothermia on the plasma
      concentration-response and biodisposition of rocuronium were investigated.
      Neuromuscular function was monitored mechanomyographically. Plasma and urine
      concentrations of rocuronium were determined by high performance liquid
      chromatography. Hypothermic cardiopulmonary bypass prolonged the duration of
      action of maintenance doses and altered the plasma concentration-response
      relationship. The elimination and distribution half-lives, following the last
      maintenance dose after rewarming, and the urinary excretion of rocuronium were
      similar to values obtained during normothermia. A diminished hepatic uptake and
      storage in the liver of rocuronium during hypothermia may explain the more
      pronounced prolongation of the duration compared to that of other steroidal
      neuromuscular blocking agents.

PMID- 8557016
TI  - The influence of hypothermia (surface cooling) on the time-course of action and
      on the pharmacokinetics of rocuronium in humans.
AB  - Hypothermia prolongs the time-course of action of non-depolarizing neuromuscular
      blocking agents. The mechanism, however, is unknown. We studied the influence of
      hypothermia (by surface cooling, nasopharyngeal temperature < or = 31 degrees C)
      on the time-course of action and on the pharmacokinetics of rocuronium in humans.
      Nineteen neurosurgical patients were divided into hypothermic and normothermic
      groups. Hypothermia (30.4 +/- 0.8 degrees C (mean +/- SD)) increased the duration
      of action, temperature dependently, and delayed the recovery. Hypothermia reduced
      the plasma clearance significantly (2.17 +/- 0.62 vs. 4.26 +/- 0.50 mL kg-1 min
      1, P = 0.004), did not change the volume of distribution (224 +/- 64 vs. 232 +/-
      60 mL kg-1 min-1, P = 1.0), and prolonged the mean residence time (108 +/- 39 vs.
      56 +/- 19 mL kg-1 min-1, P = 0.01). We conclude that hypothermia prolongs the
      duration of action of rocuronium and delays spontaneous recovery and that altered
      pharmacokinetics, such as a decreased clearance, play an important role in this.

PMID- 8557017
TI  - Vitamin B12 deficiency and the fortification of food with folic acid.

PMID- 8557018
TI  - Iron absorption from the whole diet. Relation to meal composition, iron
      requirements and iron stores.
AB  - OBJECTIVE: To validate a new method of measuring iron absorption from the whole
      diet over several days, to compare iron absorption from two types of diets and to
      relate iron absorption to iron requirements and iron stores. DESIGN: Iron
      absorption from two diets was studied in 21 healthy young women. All non-haem
      iron in all meals was labelled to the same specific activity with an extrinsic
      radio-labelled iron tracer. Haem iron absorption was calculated from the amount
      of haem iron and absorption from a reference dose of iron. RESULTS: Iron
      absorption was concordant with individual iron requirements measured from
      menstrual blood losses and body weights. Total iron absorption from one diet
      designed to be highly bioavailable, would cover iron requirements in about 94% of
      menstruating women. Iron absorption was reduced by half from a diet with less
      meat, more phytate and more calcium with main meals. This type of diet would
      cover iron requirements in only 65% of adult menstruating women. For both diets
      there was a marked reduction in iron absorption with increasing serum ferritin.
      Iron balance was not positive above a serum ferritin of about 60 micrograms/l.
      CONCLUSIONS: Bioavailability of dietary iron is a key factor in iron nutrition. A
      diet with much lean meat, ascorbic acid and a low phytate content can cover iron
      requirements in most non-pregnant women. The powerful control of iron absorption
      implies that dietary iron overload cannot develop in normal subjects, even with
      diets having high iron content or high bioavailability.

PMID- 8557019
TI  - Seasonal variations in energy balance among agriculturalists in central Mali:
      compromise or adaptation?
AB  - OBJECTIVE: This paper considers whether seasonal variations in the energy balance
      of adult agriculturalists in Central Mali exceed acceptable risk, or whether they
      represent a short-term adaptive response without functional consequence. DESIGN:
      Prospective/longitudinal study design. SETTING: Agricultural village in rural
      Mali. SUBJECTS: From a total population of 166 adults aged > or = 16 years, two
      cohorts of 63 men and 73 non-pregnant women with complete records were retained
      for analysis. INTERVENTIONS: Over a 12-month period, monthly anthropometry and
      biweekly retrospective assessments of morbidity were made on every adult in the
      sample. Direct measures of household food consumption were collected twice in
      harvest, dry and rainy seasons respectively. Continuous 15-h observations of time
      use and work intensity were conducted on a sub-sample of active adults and used
      to calculate mean seasonal energy expenditure. RESULTS: Energy balance as
      measured by body mass index (BMI; kg/m2) declines significantly in the rainy
      season (P < 0.01), corresponding to a seasonal weight loss of 2-3 kg. A similar
      seasonal trend in % body fat (P < 0.0001) suggests that most of this loss
      represents adipose tissue. A rainy season increase in arm muscle area (AMA)
      implies that there is no seasonal compromise in lean tissue. Among men and women
      with BMI > 18.5, seasonal fat loss is significantly greater than their leaner
      counterparts. Considering the likely determinants of variations in energy
      balance, an increase in the duration and incidence of adult morbidity is
      observed; however, no significant intercorrelations exist between it and seasonal
      nutritional indices. Comparing trends in energy expenditure and intake, a
      disturbance in energy homeostasis is apparent as energy expenditure increases in
      the rainy season relative to constant household food consumption across seasons.
      While seasonal variations in energy expenditure are not as dramatic in the female
      sample, they appear to have less opportunity to recover from so-called 'heavy'
      levels of expenditure experienced in successive dry and rainy seasons. Periods of
      'light' activity in both harvest and dry seasons provide the male sample with a
      reasonable length of time in which to reconstitute energy stores after the
      physical demands of the rainy season. CONCLUSIONS: In the year of study, the
      modest loss of body fat recorded in the rainy season (< 5% body mass) represents
      a successful physiological response to energy imbalance, and is unlikely to
      compromise adult productive and reproductive function.

PMID- 8557020
TI  - Body fatness in active individuals reporting low lipid and alcohol intake.
AB  - OBJECTIVES: To evaluate body fatness in subjects complying with common public
      health guidelines for lipid and alcohol intake as well as physical activity
      participation. SUBJECTS: A sample of 358 male subjects who participated in phase
      1 of the Quebec Family Study. DESIGN: The association between adiposity, lipid
      and alcohol intake and physical activity participation was analyzed in the
      overall sample. A comparison of body fatness in individuals adhering or not to
      public health recommendations was also performed. RESULTS: Significant positive
      correlations were observed between the percentage of dietary energy as lipid and
      adiposity indicators. Accordingly, subjects classified as low-fat consumers
      displayed significantly lower levels of fat mass and subcutaneous adiposity
      compared to high-fat consumers. When subjects reporting low lipid and alcohol
      intake and regular participation in vigorous physical activities were compared to
      those exhibiting opposite behaviors, the between-group difference in subcutaneous
      adiposity was doubled and this was essentially explained by an increase in the
      difference for truncal subcutaneous adiposity. CONCLUSION: These results indicate
      that the adherence to a lifestyle characterized by high-fat and alcohol intake as
      well as sedentariness promotes fat gain, particularly in the trunk area.

PMID- 8557022
TI  - Nutrition guidance by primary-care physicians: perceived barriers and low
      involvement.
AB  - OBJECTIVE: To investigate the activities of general practitioners (GPs) in
      nutritional matters and the factors that influence their attitudes, knowledge and
      behaviour, especially perceived barriers. DESIGN: Postal questionnaires (result
      of focus group discussions and in-depth interviews) were sent to a nationwide
      random sample of GPs in the Netherlands. SUBJECTS: 1000 GPs, in practice for
      between 5 and 15 years. MAIN OUTCOME MEASURES: The identification of GPs'
      perceived barriers to nutritional guidance of their patients, their nutritional
      attitudes and behaviours. RESULTS: Net response rate was 64% (633/990). GPs
      perceived smoking to be the greatest health hazard, followed by dietary pattern
      and genome. 70% expressed considerable interest in the role of nutrition in
      health. In daily practice nutrition plays a minor role in the work of the GP. 28%
      of GPs gave daily nutrition information to about 10% of their patients and 48% to
      about 5% of their patients. It is found that GPs do perceive strong barriers of
      being involved in nutrition issues during their practice. The most important
      barriers expressed were: not being trained in nutrition, lack of time to address
      nutrition issues and the perception that patients lack motivation to change
      lifestyle and/or dietary patterns. CONCLUSIONS: The involvement of GPs in
      nutritional matters is very low. The fact that lack of training is considered as
      the most important barrier is, however, unexpected. This finding offers
      possibilities for improvement in which in-service courses and inter-active
      distant-learning programmes on nutrition for GPs should get special attention.

PMID- 8557021
TI  - Assessment of dietary phylloquinone intake and vitamin K status in postmenopausal
      women.
AB  - OBJECTIVE: To examine the relationship between dietary phylloquinone intake and
      vitamin K status of postmenopausal Caucasian women. DESIGN: Cross-sectional
      study, in which dietary intake was estimated using weighed record techniques and
      vitamin K status was measured by a single plasma phylloquinone concentration and
      24-h urinary gamma-carboxyglutamic acid (Gla) excretion. SETTING: The metabolic
      research unit at the Jean Mayer USDA Human Nutrition Research Center on Aging at
      Tufts University, Boston, MA. SUBJECTS: 402 healthy postmenopausal Caucasian
      women who were participating in a randomized trial to determine the effect of
      calcium supplementation on bone loss. Of the original group, 362 had complete
      weighed diet records, 358 had corresponding plasma phylloquinone concentrations,
      and 346 had corresponding urinary Gla measurements. RESULTS: There was a
      significant correlation (r = 0.13, P = 0.01) between total dietary intake of
      phylloquinone (geometric mean = 89 micrograms/day) and plasma phylloquinone
      levels (mean = 1.12 nmol/l). Dietary intake was neither correlated with urinary
      Gla excretion (mean = 4.0 mumol/mmol creatinine) nor did it vary by season. The
      ratio of intra- to interindividual variance in phylloquinone intake was 2.6, from
      which it was estimated that 5 days of independent recording is necessary to
      estimate true usual dietary intake, assuming a correlation of 0.8. CONCLUSIONS: A
      weighed record has the potential to be a reliable method for estimating dietary
      intakes of vitamin K which relate to plasma phylloquinone levels used as an
      indicator of vitamin K status in postmenopausal Caucasian women.

PMID- 8557023
TI  - Dietary intake in five ageing cohorts of men in Finland, Italy and The
      Netherlands.
AB  - OBJECTIVE: To obtain insight into dietary habits of elderly people and how these
      habits have evolved from middle to old age. DESIGN: Cross-sectional study of
      dietary patterns around 1990; retrospective cohort study of changes in dietary
      intake since middle age. SETTING: Five cohorts: East and West Finland, Zutphen
      (Netherlands), Crevalcore (Italy), and Montegiorgo (Italy). SUBJECTS: Men aged 70
      90 years around 1990. METHODS: Food intake was estimated using a cross-check
      dietary history adjusted to the local situation. RESULTS: (i) Cross-sectional:
      Significant differences were observed between the countries for all food groups,
      energy and nutrients (P < 0.05). The Finnish diet was characterised by a high
      consumption of animal products and potatoes, the Italian diet by a high
      consumption of cereals, vegetables, fruits and alcohol. The Dutch diet was
      generally intermediate. (ii) Longitudinal: The decrease in energy intake since
      middle age varied from 4.2 MJ/day in the Finnish cohorts to 2.1 MJ/day in Italy.
      Also the consumption of most food groups decreased but the consumption of
      vegetables and fruits increased. Saturated fatty acid intake decreased by 3 E% in
      the Finnish cohorts and decreased by < 1 E% in Italy. Alcohol intake decreased by
      approximately 7 E% in Italy while it increased by 2.5 E% in the Netherlands.
      CONCLUSIONS: Although the general patterns of dietary intake of the different
      cultures still can be recognised at old age, the variation between them has
      become smaller. Compared to their dietary intake at middle age, however, the
      dietary pattern of the Finnish and Dutch cohorts has changed slightly in the
      direction of a healthy diet, while the diet of the Italian men remained
      Mediterranean, and thus more healthy, at old age.

PMID- 8557024
TI  - Plasma concentrations of carotenoids and antioxidant vitamins in Scottish males:
      influences of smoking.
AB  - OBJECTIVE: To quantify the major carotenoids in plasma of Scottish males and
      establish which were affected by habitual smoking. DESIGN: Concentrations of
      carotenoids, vitamin C and vitamin E (alpha and gamma-tocopherol) were determined
      in plasma samples from 50 fasted male smokers and 50 age-matched males who had
      never smoked (aged 50-59 years). RESULTS: Significantly less alpha-carotene, beta
      carotene and beta-cryptoxanthin and vitamin C in plasma of smokers than in never
      smokers whereas concentrations of lycopene, lutein/zeaxanthin, phytofluene and
      vitamin E were similar between the groups. CONCLUSION: Whether lower carotenoid
      and vitamin C concentrations in smokers than never-smokers reflect different
      dietary patterns or increased metabolic turnover is unclear but smokers may
      benefit from increased carotenoid and vitamin C intakes.

PMID- 8557025
TI  - Antioxidant properties of zinc.

PMID- 8557026
TI  - Crystal structure of the flavohemoglobin from Alcaligenes eutrophus at 1.75 A
      resolution.
AB  - The molecular structure of the flavohemoglobin from Alcaligenes eutrophus has
      been determined to a resolution of 1.75 A and refined to an R-factor of 19.6%.
      The protein comprises two fused modules: a heme binding module, which belongs to
      the globin family, and an FAD binding oxidoreductase module, which adopts a fold
      like ferredoxin reductase. The most striking deviation of the bacterial globin
      structure from those of other species is the movement of helix E in a way to
      provide more space in the vicinity of the distal heme binding site. A comparison
      with other members of the ferredoxin reductase family shows similar tertiary
      structures for the individual FAD and NAD binding domains but largely different
      interdomain orientations. The heme and FAD molecules approach each other to a
      minimal distance of 6.3 A and adopt an interplanar angle of 80 degrees. The
      electron transfer from FAD to heme occurs in a predominantly polar environment
      and may occur directly or be mediated by a water molecule.

PMID- 8557027
TI  - DNA packaging orders the membrane of bacteriophage PRD1.
AB  - Bacteriophage PRD1 contains a linear dsDNA genome enclosed by a lipid membrane
      lying within a protein coat. Determination of the structure of the detergent
      treated particle to 2 nm by cryo-electron microscopy and three-dimensional
      reconstruction has defined the position of the major coat protein P3. The coat
      contains 240 copies of trimeric P3 packed into positions of local 6-fold symmetry
      on a T = 25 lattice. The three-dimensional structures of the PRD1 virion and a
      DNA packaging mutant to a resolution of 2.8 nm have revealed specific
      interactions between the coat and the underlying membrane. The membrane is
      clearly visible as two leaflets separated by 2 nm and spanned by transmembrane
      density. The size of the coat does not change upon DNA packaging. Instead, the
      number of interactions seen between the protein shell and the membrane and the
      order of the membrane components increase. Thus the membrane of PRD1 plays a role
      in assembly which is akin to that played by the nucleocapsid in other membrane
      viruses.

PMID- 8557028
TI  - A highly recombinogenic system for the recovery of infectious Sendai
      paramyxovirus from cDNA: generation of a novel copy-back nondefective interfering
      virus.
AB  - We have recovered infectious Sendai virus (SeV) from full-length cDNA (FL-3) by
      transfecting this cDNA and pGEM plasmids expressing the nucleocapsid protein
      (NP), phosphoprotein and large proteins into cells infected with a vaccinia virus
      which expresses T7 RNA polymerase. These cells were then injected into chicken
      eggs, in which SeV grows to very high titers. FL-3 was marked with a BglII site
      in the leader region and an NsiI site (ATGCAT) in the 5' nontranslated region of
      the NP gene, creating a new, out-of-frame, 5' proximal AUG. All the virus stocks
      generated eventually removed this impediment to NP expression, by either point
      mutation or recombination between FL-3 and pGEM-NP. The recovery system was found
      to be highly recombinogenic. Even in the absence of selective pressure, one in 20
      of the recombinant SeV generated had exchanged the NP gene of FL-3 with that of
      pGEM-NP. When a fifth plasmid containing a new genomic 3' end without the
      presumably deleterious BglII site was included as another target for
      recombination, the new genomic 3' end was found in the recombinant SeV in 12 out
      of 12 recoveries. Using this approach, a novel copy-back nondefective virus was
      generated which interferes with wild-type virus replication.

PMID- 8557029
TI  - Deficient signaling in mice devoid of double-stranded RNA-dependent protein
      kinase.
AB  - Double-stranded RNA-dependent protein kinase (PKR) has been implicated in
      interferon (IFN) induction, antiviral response and tumor suppression. We have
      generated mice devoid of functional PKR (Pkr%). Although the mice are physically
      normal and the induction of type I IFN genes by poly(I).poly(C) (pIC) and virus
      is unimpaired, the antiviral response induced by IFN-gamma and pIC was
      diminished. However, in embryo fibroblasts from Pkr knockout mice, the induction
      of type I IFN as well as the activation of NF-kappa B by pIC, were strongly
      impaired but restored by priming with IFN. Thus, PKR is not directly essential
      for responses to pIC, and a pIC-responsive system independent of PKR is induced
      by IFN. No evidence of the tumor suppressor activity of PKR was demonstrated.

PMID- 8557030
TI  - E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast
      cancers.
AB  - Compelling experimental evidence exists for a potent invasion suppressor role of
      the cell-cell adhesion molecule E-cadherin. In addition, a tumour suppressor
      effect has been suggested for E-cadherin. In human cancers, partial or complete
      loss of E-cadherin expression correlates with malignancy. To investigate the
      molecular basis for this altered expression we developed a comprehensive PCR/SSCP
      mutation screen for the human E-cadherin gene. For 49 breast cancer patients the
      occurrence of tumour-specific mutations in the E-cadherin gene was examined. No
      relevant DNA changes were encountered in any of 42 infiltrative ductal or
      medullary breast carcinoma samples. In contrast, four out of seven infiltrative
      lobular breast carcinomas harboured protein truncation mutations (three nonsense
      and one frameshift) in the extracellular part of the E-cadherin protein. Each of
      the four lobular carcinomas with E-cadherin mutations showed tumour-specific loss
      of heterozygosity of chromosomal region 16q22.1 containing the E-cadherin locus.
      In compliance with this, no E-cadherin expression was detectable by
      immunohistochemistry in these four tumours. These findings offer a molecular
      explanation for the typical scattered tumour cell growth in infiltrative lobular
      breast cancer.

PMID- 8557031
TI  - CAT5, a new gene necessary for derepression of gluconeogenic enzymes in
      Saccharomyces cerevisiae.
AB  - PCK1 encoding phosphoenolpyruvate carboxykinase is transcriptionally regulated by
      two upstream activating elements. By screening for mutants that failed to
      derepress a UAS2PCK1-CYC1-lacZ reporter gene we isolated the new recessive
      derepression mutation cat5. The CAT5 gene encodes a protein of 272 amino acids
      showing a 42% identity to the ZC395.2 gene product of Caenorhabditis elegans
      whose function is unknown. Deletion of CAT5 caused a complete loss of glucose
      derepression affecting gluconeogenic key enzymes. Respiration, but not
      mitochondrial cytochrome c oxidase activity, was also affected. CAT5 expression
      is 5- to 6-fold repressed by glucose, and CAT5 transcriptional activation was
      dependent on CAT1 (SNF1), CAT8 and CAT5 itself. The CAT5 gene is necessary for
      UAS1PCK1 and UAS2PCK1 protein binding since a carbon source-specific interaction
      was no longer detectable in cat5 mutants. Glucose derepression of gluconeogenesis
      depends on the active Cat1 (Snf1) protein kinase and the Cat8 zinc cluster
      activator. Mig1p-independent overexpression of CAT8 did not stimulate activation
      of gluconeogenic promoters in cat1 and in cat5 mutants. Since Cat8p multicopy
      expression suppresses the ethanol growth deficiency in cat1 (snf1) mutants, these
      results indicate that activation of Cat8p by the Cat1p (Snf1p) kinase and the
      Cat5p protein might be necessary for release from glucose repression.

PMID- 8557032
TI  - NF-M (chicken C/EBP beta) induces eosinophilic differentiation and apoptosis in a
      hematopoietic progenitor cell line.
AB  - CAAT/enhancer binding proteins (C/EBPs) are transcriptional activators implicated
      in the differentiation processes of various cell lineages. We have shown earlier
      that NF-M, the chicken homolog of C/EBP beta, is specifically expressed in
      myelomonocytic and eosinophilic cells of the hematopoietic system. To investigate
      the role of NF-M in hematopoietic cell lineage commitment, we constructed a
      conditional form of the protein by fusing it to the hormone binding domain of the
      human estrogen receptor. This construct was stably expressed in a multipotent
      progenitor cell line transformed by the Myb-Ets oncoprotein. We report here that
      both NF-M-dependent promoter constructs and resident genes could be activated by
      addition of beta-estradiol to the NF-M-estrogen receptor expressing progenitors.
      At the same time, we observed a down-regulation of progenitor-specific surface
      markers and the up-regulation of differentiation markers restricted to the
      eosinophil and myeloid lineages. In addition to the onset of differentiation,
      cell death was induced with typical apoptotic features. Our results suggest that
      NF-M plays an important role in commitment along the eosinophil lineage and in
      the induction of apoptosis.

PMID- 8557033
TI  - Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis.
AB  - Activation of the cell surface receptor Fas/APO-1 (CD95) induces apoptosis in
      lymphocytes and regulates immune responses. The cytoplasmic membrane protein Bcl
      2 inhibits lymphocyte killing by diverse cytotoxic agents, but we found it
      provided little protection against Fas/APO-1-transduced apoptosis in B lymphoid
      cell lines, thymocytes and activated T cells. In contrast, the cowpox virus
      protease inhibitor CrmA blocked Fas/APO-1-transduced apoptosis, but did not
      affect cell death induced by gamma-radiation or serum deprivation. Signalling
      through Fas/APO-1 did not down-regulate Bcl-2 or induce its antagonists Bax and
      Bcl-xS. In Fas/APO-1-deficient lpr mice, Bcl-2 transgenes markedly augmented the
      survival of antigen-activated T cells and the abnormal accumulation of
      lymphocytes (although they did not interfere with deletion of auto-reactive cells
      in the thymus). These data raise the possibility that Bcl-2 and Fas/APO-1
      regulate distinct pathways to lymphocyte apoptosis.

PMID- 8557035
TI  - Evidence for a role of MEK and MAPK during signal transduction by protein kinase
      C zeta.
AB  - Protein kinase C zeta (zeta PKC) is critically involved in the control of a
      number of cell functions, including proliferation and nuclear factor kappa B (NF
      kappa B) activation. Previous studies indicate that zeta PKC is an important step
      downstream of Ras in the mitogenic cascade. The stimulation of Ras initiates a
      kinase cascade that culminates in the activation of MAP kinase (MAPK), which is
      required for cell growth. MAPK is activated by phosphorylation by another kinase
      named MAPK kinase (MEK), which is the substrate of a number of Ras-activated
      serine/threonine kinases such as c-Raf-1 and B-Raf. We show here that MAPK and
      MEK are activated in vivo by an active mutant of zeta PKC, and that a kinase
      defective dominant negative mutant of zeta PKC dramatically impairs the
      activation of both MEK and MAPK by serum and tumour necrosis factor (TNF alpha).
      The stimulation of other kinases, such as stress-activated protein kinase (SAPK)
      or p70S6K, is shown here to be independent of zeta PKC. The importance of
      MEK/MAPK in the signalling mechanisms activated by zeta PKC was addressed by
      using the activation of a kappa B-dependent promoter as a biological read-out of
      zeta PKC.

PMID- 8557034
TI  - Proteolytic activation of protein kinase C delta by an ICE-like protease in
      apoptotic cells.
AB  - These studies demonstrate that treatment of human U-937 cells with ionizing
      radiation (IR) is associated with activation of a cytoplasmic myelin basic
      protein (MBP) kinase. Characterization of the kinase by gel filtration and in-gel
      kinase assays support activation of a 40 kDa protein. Substrate and inhibitor
      studies further support the induction of protein kinase C (PKC)-like activity.
      The results of N-terminal amino acid sequencing of the purified protein
      demonstrate identity of the kinase with an internal region of PKC delta.
      Immunoblot analysis was used to confirm proteolytic cleavage of intact 78 kDa PKC
      delta in control cells to the 40 kDa C-terminal fragment after IR exposure. The
      finding that both IR-induced proteolytic activation of PKC delta and
      endonucleolytic DNA fragmentation are blocked by Bcl-2 and Bcl-xL supports an
      association with physiological cell death (PCD). Moreover, cleavage of PKC delta
      occurs adjacent to aspartic acid at a site (QDN) similar to that involved in
      proteolytic activation of interleukin-1 beta converting enzyme (ICE). The
      specific tetrapeptide ICE inhibitor (YVAD) blocked both proteolytic activation of
      PKC delta and internucleosomal DNA fragmentation in IR-treated cells. These
      findings demonstrate that PCD is associated with proteolytic activation of PKC
      delta by an ICE-like protease.

PMID- 8557037
TI  - Identification of a cdk-activating kinase in fission yeast.
AB  - We have identified a second cyclin-dependent kinase (cdk) in fission yeast, crk1,
      which encodes a 335 amino acid protein that is most closely related to the KIN28
      gene product from Saccharomyces cerevisiae and to a cdk activating kinase (CAK)
      encoded by the MO15 gene from Xenopus laevis, crk1 is essential for viability and
      delta crk1 cells arrest with septa and condensed chromatin. We show that Crk1
      associates with the Mcs2 mitotic catastrophe suppressor, a cyclin H-like
      molecule, and overexpression of crk1 rescues the cell-cycle arrest defect of a
      mcs2-75 cdc2-3w cdc25-22 triple mutant at high temperature. The Crk1-Mcs2 complex
      possesses CAK activity in vitro in that it phosphorylates human Cdk2 on Thr160
      which results in its activation in the presence of cyclin A. In addition Crk1
      Mcs2 effectively phosphorylates a peptide corresponding to the C-terminal repeat
      domain (CTD) of RNA polymerase II. We demonstrate that crk1 is allelic to the
      mcs6 mitotic catastrophe suppressor and that the X.laevis MO15 gene rescues the
      cell-cycle arrest of an mcs6-13 cdc2-3w cdc25-22 at high temperature. Together
      these data suggest that the Crk1-Mcs2 complex is a CAK that interacts genetically
      with Cdc2 in fission yeast.

PMID- 8557036
TI  - Schizosaccharomyces pombe Mop1-Mcs2 is related to mammalian CAK.
AB  - The cyclin-dependent kinase (CDK)-activating kinase, CAK, from mammals and
      amphibians consists of MO15/CDK7 and cyclin H, a complex which has been
      identified also as a RNA polymerase II C-terminal domain (CTD) kinase. While the
      Schizosaccharomyces pombe cdc2 gene product also requires an activating
      phosphorylation, the enzyme responsible has not been identified. We have isolated
      an essential S.pombe gene, mop1, whose product is closely related to MO15 and to
      Saccharomyces cerevisiae Kin28. The functional similarity of Mop1 and MO15 is
      reflected in the ability of MO15 to rescue a mop1 null allele. This suggests that
      Mop1 would be a CDK, and indeed Mop1 associates with a previously characterized
      cyclin H-related cyclin Mcs2 of S.pombe. Also, Mop1 and Mcs2 can associate with
      the heterologous partners human cyclin H and MO15, respectively. Moreover, the
      rescue of a temperature-sensitive mcs2 strain by expression of mop1+ demonstrates
      a genetic interaction between mop1 and mcs2. In a functional assay,
      immunoprecipitated Mop1-Mcs2 acts both as an RNA polymerase II CTD kinase and as
      a CAK. The CAK activity of Mop1-Mcs2 distinguishes it from the related CDK-cyclin
      pair Kin28-Ccl1 from S.cerevisiae, and supports the notion that Mop1-Mcs2 may
      represent a homolog of MO15-cyclin H in S.pombe with apparent dual roles as a RNA
      polymerase CTD kinase and as a CAK.

PMID- 8557038
TI  - Physical and functional interactions between p53 and cell cycle co-operating
      transcription factors, E2F1 and DP1.
AB  - One way in which wild-type p53 is able to regulate cell cycle progression is
      thought to be via the induction of its downstream target gene Waf1/CIP1, thus
      indirectly regulating the transcriptional activity of E2F. The E2F transcription
      factors are known to be key effectors of the cell cycle. We report here that
      there is a physical and functional interaction between p53 and two of the
      components of the E2F transcription factors, E2F1 and DP1. The expression of wild
      type p53 can inhibit the transcriptional activity of E2F, and the expression of
      both E2F1 and DP1 can also downregulate p53-dependent transcription. The
      transcriptional activity of p53 is known to be inhibited by the direct binding of
      mdm2, but we demonstrate here that both E2F1 and DP1 can inhibit p53
      transcriptional activity independently of mdm2. Detailed studies of protein
      protein interactions have provided evidence that E2F1 and its co-operating factor
      DP1 can complex with p53 both in vitro and in vivo.

PMID- 8557039
TI  - Schizosaccharomyces pombe atf1+ encodes a transcription factor required for
      sexual development and entry into stationary phase.
AB  - We describe the identification and characterization of a transcription factor
      encoded by the atf1+ gene of the fission yeast Schizosaccharomyces pombe. The
      factor Atf1, contains a bZIP domain at its C-terminus with strong homology to
      members of the ATF/CREB family of mammalian factors and in vitro binds
      specifically to ATF/CRE recognition sites. Furthermore the ATF-like binding
      activity detected in extracts from fission yeast cells is entirely lost upon
      deletion of the atf1+ gene. Upon growth to saturation, fission yeast cells exit
      the mitotic cycle and enter a G0-like stationary phase. However, on rich medium,
      entry of atf1- cells into stationary phase is restricted and they rapidly lose
      viability; this does not occur on minimal medium unless cAMP levels are raised.
      Thus stationary phase entry appears to be regulated negatively by cAMP and
      positively by Atf1. atf1- cells are also sterile and this sterility appears to be
      due to a combination of two defects: first, upon nitrogen starvation the majority
      of atf1- cells fail to arrest in the G1 phase of the cell cycle and second, the
      induction of ste11+ expression is lost. Thus expression of ste11+ represents a
      second example of an event that is negatively regulated by the cAMP pathway and
      positively regulated by Atf1. Despite their close association however, these two
      regulatory pathways function independently and Atf1 activity is not directly
      modulated by cAMP levels or mutations that alter the activity of components of
      the cAMP signalling pathway. Thus Atf1 is a transcription factor that plays an
      important role in the response of cells to adverse environmental conditions,
      which is to exit the mitotic cell cycle and either sexually differentiate or
      enter a resting state.

PMID- 8557041
TI  - Co-operative interaction between the initiator E1 and the transcriptional
      activator E2 is required for replicator specific DNA replication of bovine
      papillomavirus in vivo and in vitro.
AB  - The E1 polypeptide from bovine papillomavirus binds to the origin of replication
      (ori) and possesses the activities attributed to initiator proteins. E1 is also
      the only viral protein required for replication in a cell-free replication
      system. Replication in vivo, however, absolutely requires in addition the viral
      transcription factor E2. We demonstrate that the basis for this distinction
      between in vitro and in vivo requirements is the limited sequence specificity of
      the E1 protein. E1 and E2, which bind the ori individually with low sequence
      specificity, together bind with greatly increased sequence specificity. This
      combinatorial effect provides a function for the involvement of transcriptional
      activation domains in replication and suggests common mechanisms of action for
      transcription factors in both transcription and replication. It also provides a
      possible explanation for the differential specificity that is observed for
      auxiliary transcription factors in vivo.

PMID- 8557040
TI  - Chromosomal translocations cause deregulated BCL6 expression by promoter
      substitution in B cell lymphoma.
AB  - The BCL6 gene codes for a zinc-finger transcription factor and is involved in
      chromosomal rearrangements in 30-40% of diffuse large-cell lymphoma (DLCL). These
      rearrangements cluster within the 5' regulatory region of BCL6 spanning its first
      non-coding exon. To determine the functional consequences of these alterations,
      we have analyzed the structure of the rearranged BCL6 alleles and their
      corresponding RNA and protein species in two DLCL biopsies and one tumor cell
      line which carried the t(3;14)(q27;q32) translocation involving the BCL6 and
      immunoglobulin heavy-chain (IgH) loci. In all three cases, the breakpoints were
      mapped within the IgH switch region and the BCL6 first intron, leading to the
      juxtaposition of part of the IgH locus upstream and in the same transcriptional
      orientation to the BCL6 coding exons. An analysis of cDNA clones showed that
      these recombinations generate chimeric IgH-BCL6 transcripts which initiated from
      IgH germline transcript promoters (I mu or I gamma 3), but retain a normal BCL6
      coding domain. In the tumor cell line, the chimeric I gamma 3-BCL6 allele, but
      not the germline BCL6 gene, was transcriptionally active and produced a normal
      BCL6 protein. These findings indicate that t(3;14) translocations alter BCL6
      expression by promoter substitution and imply that the consequence of these
      alterations is the deregulated expression of a normal BCL6 protein.

PMID- 8557042
TI  - Immunoglobulin gene transcription ceases upon deletion of a distant enhancer.
AB  - The tissue-specific E mu enhancer within the immunoglobulin heavy chain (IgH)
      locus has recently been shown to be essential for efficient V region gene
      assembly in early B lineage cells. However, we and others have shown that late
      stage, Ig-secreting cells can produce IgH in the absence of E mu. In the present
      study we have explored the notion that another enhancer found in the far 3'
      region of the IgH locus (3' alpha E) takes on an important regulatory role in
      cells that have reached this terminal stage in B cell development. The technique
      of homologous recombination was used to disrupt the 3' alpha E region in an E mu
      deficient, Ig gamma 2a-secreting cell line. Loss of 3' alpha E completely
      abolished Ig heavy chain gene expression, demonstrating that transcription of
      this gene was dependent upon sequences that reside over 70 kb downstream. The
      ability of these sequences to function efficiently in the absence of E mu may
      also provide an explanation for deregulated c-myc expression in many Ig-secreting
      tumors.

PMID- 8557043
TI  - Molecular analysis of a steroid-induced regulatory hierarchy: the Drosophila E74A
      protein directly regulates L71-6 transcription.
AB  - Steroid hormones orchestrate the growth and development of higher organisms by
      directing spatially and temporally coordinated programs of gene expression. These
      changes in gene activity can be visualized in Drosophila by virtue of its giant
      salivary gland polytene chromosomes. A small set of early puffs are induced
      directly by the steroid hormone ecdysone. The proteins encoded by these puffs
      appear to induce many late secondary-response puffs as the animal begins to
      undergo metamorphosis. Here we report that the ETS domain DNA-binding protein
      encoded by the E74A early gene directly induces L71-6 late gene transcription. We
      identify four strong E74A binding sites within the 5' region of L71-6 demonstrate
      that these sites are essential for proper L71-6 induction at puparium formation.
      These studies provide a direct link between a steroid-induced transcription
      factor and the activation of a secondary-response promoter, indicating that
      steroid signals in higher organisms can be transduced and amplified through
      regulatory hierarchies.

PMID- 8557044
TI  - pipsqueak encodes a novel nuclear protein required downstream of seven-up for the
      development of photoreceptors R3 and R4.
AB  - Photoreceptor induction in the Drosophila eye is mediated by activation of the
      Ras signal transduction cascade. Although this process is well understood, little
      is known about how the diversity of photoreceptor subtypes is generated. The
      pipsqueak (psq) gene is expressed at high levels in the R3/R4 precursors during
      eye development and this expression depends on seven-up (svp) gene function.
      Moreover, strong psq alleles are dominant suppressors of a svp-induced cone cell
      transformation phenotype. Although the gene was previously identified and
      described as a member of the maternal posterior group of genes, the strong
      semilethal alleles isolated here demonstrate a specific requirement for psq
      function downstream of svp for the development of photoreceptors R3/R4. The gene
      has three independent 5' ends and codes for several nuclear protein isoforms,
      some containing the POZ domain which has been implicated in protein-protein
      interactions. Interestingly, all viable alleles with a maternal posterior group
      phenotype cluster around one specific 5' exon, while all semilethal alleles have
      lesions which map to a different alternative 5' exon.

PMID- 8557045
TI  - Effects of the su(Hw) insulator protein on the expression of the divergently
      transcribed Drosophila yolk protein genes.
AB  - The suppressor of Hairy-wing [su(Hw)] protein mediates the mutagenic effects of
      the gypsy retrotransposon by blocking enhancer activity. These repressive effects
      are general, can occur over long distances and require that the su(Hw) protein is
      bound between the affected enhancer and promoter. The effects of the su(Hw)
      binding region on yolk protein (yp) gene expression were determined. These genes
      are regulated by shared enhancers in the intergenic region, which provided a
      method to examine whether an enhancer blocked by the su(Hw) protein remained
      functional. We demonstrate that a blocked enhancer is completely active,
      supporting the proposal that the su(Hw) protein is an insulator protein that acts
      by forming a new boundary in a pre-existing chromatin domain, thereby preventing
      the interaction of regulatory elements located upstream of the insertion site
      with the promoter. In addition, we found that yp promoter function is not
      diminished by sharing enhancers, suggesting that these enhancers are not rate
      limiting for transcriptional activation. Lastly, our data indicate that yp
      promoter activity is interdependent, such that transcription from one promoter
      influences the level of activity of the linked promoter.

PMID- 8557046
TI  - Antagonizing the Spemann organizer: role of the homeobox gene Xvent-1.
AB  - We have identified a novel homeobox gene, Xvent-1, that is differentially
      expressed in the ventral marginal zone of the early Xenopus gastrula. Evidence is
      presented from mRNA microinjection experiments for a role for this gene in
      dorsoventral patterning of mesoderm. First, Xvent-1 is induced by BMP-4, a gene
      known to be a key regulator of ventral mesoderm development. Second, Xvent-1 and
      the organizer-specific gene goosecoid are able to interact, directly or
      indirectly, in a cross-regulatory loop suppressing each other's expression,
      consistent with their mutually exclusive expression in the marginal zone. Third,
      microinjection of Xvent-1 mRNA ventralizes dorsal mesoderm. The results suggest
      that Xvent-1 functions in a ventral signaling pathway that maintains the ventral
      mesodermal state and antagonizes the Spemann organizer.

PMID- 8557047
TI  - Structure of the even-skipped homeodomain complexed to AT-rich DNA: new
      perspectives on homeodomain specificity.
AB  - even-skipped is a homeobox gene important in controlling segment patterning in
      the embryonic fruit fly. Its homeobox encodes a DNA binding domain which binds
      with similar affinities to two DNA consensus sequences, one AT-rich, the other GC
      rich. We describe a crystallographic analysis of the Even-skipped homeodomain
      complexed to an AT-rich oligonucleotide at 2.0 A resolution. The structure
      reveals a novel arrangement of two homeodomains bound to one 10 bp DNA sequence
      in a tandem fashion. This arrangement suggests a mechanism for the homeoproteins'
      regulatory specificity. In addition, the functionally important residue Gln50 is
      observed in multiple conformations making direct and water-mediated hydrogen
      bonds with the DNA bases.

PMID- 8557048
TI  - Comparison of protein binding to DNA in vivo and in vitro: defining an effective
      intracellular target.
AB  - We have quantitatively evaluated the affinity of a set of target sites for the
      integration host factor (IHF) protein of Escherichia coli by their performance as
      competitors in an electrophoretic mobility shift assay. We also determined how
      well each of these sites is filled by IHF in vivo. The data show that several
      natural sites have an affinity not much greater than that required for
      intracellular occupancy. The data also indicate that very little of the IHF in a
      cell is present as free protein available for binding, suggesting that binding to
      non-specific targets dominates the operation of this system. The correlation
      between in vitro affinity and in vivo occupancy provides a ready means to assess
      the likely physiological significance of putative IHF sites. It also provides a
      general method to assess the importance of non-specific interactions by DNA
      binding proteins inside a cell.

PMID- 8557049
TI  - Cytoplasmic 3' poly(A) addition induces 5' cap ribose methylation: implications
      for translational control of maternal mRNA.
AB  - During the early development of many animal species, the expression of new
      genetic information is governed by selective translation of stored maternal
      mRNAs. In many cases, this translational activation requires cytoplasmic poly(A)
      elongation. However, how this modification at the 3' end of an mRNA stimulates
      translation from the 5' end is unknown. Here we show that cytoplasmic
      polyadenylation stimulates cap ribose methylation during progesterone-induced
      oocyte maturation in Xenopus laevis. Translational recruitment of a chimeric
      reporter mRNA that is controlled by cytoplasmic polyadenylation coincides
      temporally with cap ribose methylation during this period. In addition, the
      inhibition of cap ribose methylation by S-isobutyladenosine significantly reduces
      translational activation of a reporter mRNA without affecting the increase of
      general protein synthesis or polyadenylation during maturation. These results
      provide evidence for a functional interaction between the termini of an mRNA
      molecule and suggest that 2'-O-ribose cap methylation mediates the translational
      recruitment of maternal mRNA.

PMID- 8557050
TI  - Transmembrane orientation of signal-anchor proteins is affected by the folding
      state but not the size of the N-terminal domain.
AB  - Upon insertion of a signal-anchor protein into the endoplasmic reticulum
      membrane, either the C-terminal or the N-terminal domain is translocated across
      the membrane. Charged residues flanking the transmembrane domain are important
      determinants for this decision, but are not necessarily sufficient to generate a
      unique topology. Using a model protein that is inserted into the membrane to an
      equal extent in either orientation, we have tested the influence of the size and
      the folding state of the N-terminal domain on the insertion process. A small zinc
      finger domain or the full coding sequence of dihydrofolate reductase were fused
      to the N-terminus. These stably folding domains hindered or even prevented their
      translocation. Disruption of their structure by destabilizing mutations largely
      restored transport across the membrane. Translocation efficiency, however, did
      not depend on the size of the N-terminal domain within a range of 40-237 amino
      acids. The folding behavior of the N-terminal domain is thus an important factor
      in the topogenesis of signal-anchor proteins.

PMID- 8557051
TI  - Acidic receptor domains on both sides of the outer membrane mediate translocation
      of precursor proteins into yeast mitochondria.
AB  - Mitochondrial precursor proteins made in the cytosol bind to a hetero-oligomeric
      protein import receptor on the mitochondrial surface and then pass through the
      translocation channel across the outer membrane. This translocation step is
      accelerated by an acidic domain of the receptor subunit Mas22p, which protrudes
      into the intermembrane space. This 'trans' domain of Mas22p specifically binds
      functional mitochondrial targeting peptides with a Kd of < 1 microM and is
      required to anchor the N-terminal targeting sequence of a translocation-arrested
      precursor in the intermembrane space. If this Mas22p domain is deleted,
      respiration-driven growth of the cells is compromised and import of different
      precursors into isolated mitochondria is inhibited 3- to 8-fold. Binding of
      precursors to the mitochondrial surface appears to be mediated by cytosolically
      exposed acidic domains of the receptor subunits Mas20p and Mas22p. Translocation
      of a precursor across the outer membrane thus appears to involve sequential
      binding of the precursor's basic and amphiphilic targeting signal to acidic
      receptor domains on both sides of the membrane.

PMID- 8557052
TI  - Molecular dissection of the agonist binding site of an AMPA receptor.
AB  - Two discontinuous segments (S1 and S2), separated by membrane-associated domains,
      in ionotropic glutamate receptor (GluR) subunits show sequence similarity to
      bacterial periplasmic amino acid-binding proteins, suggesting an evolutionary and
      structural relationship. Experimental evidence arguing for and against the
      inferred extracellular location of the S1 and S2 domains in GluRs has been
      presented. Here, we report that an extracellularly expressed fusion protein
      consisting of the S1 and S2 domains of alpha-amino-5-methyl-3-hydroxyisoxazolone
      4-propionate (AMPA)-selective glutamate receptor GluR-D joined together via a
      hydrophilic linker peptide specifically reproduces the AMPA-binding properties of
      GluR-D, whereas the separately expressed segments do not bind ligand. This
      provides direct evidence that the S1 and S2 segments of GluR-D contain the
      structural determinants necessary and sufficient for selective agonist binding.
      Dissection of a functional neurotransmitter binding site as a soluble protein
      separate from the integral membrane channel will facilitate new approaches to
      analyse the structure of GluRs.

PMID- 8557053
TI  - mRNA retroposition in human cells: processed pseudogene formation.
AB  - Using a sensitive assay for detection of reverse transcription events, we
      demonstrate that human HeLa cells can 'retropose', i.e. reverse transcribe and
      integrate, the mRNA of a naive reporter gene, at a low but detectable frequency.
      Furthermore, we show that the retroposed copies have all the hallmarks of the
      processed pseudogenes naturally found in the mammalian genome: they lack intron
      and 5' promoter sequence, they have acquired a 3' poly(A) tail, and they are
      flanked by short repeats (< 15 bp) of target DNA sequence. These results
      demonstrate that human cells possess an endogenous reverse transcription
      activity, which is not restricted to transcripts of transposable elements, and
      which is likely to be involved in the formation, still ongoing, of a large
      fraction of the eukaryotic genome.

PMID- 8557054
TI  - Changes in network topology during the replication of kinetoplast DNA.
AB  - Kinetoplast DNA of Crithidia fasciculata is a network containing several thousand
      topologically interlocked DNA minicircles. In the prereplicative Form I network,
      each of the 5000 minicircles is intact and linked to an average of three
      neighbors (i.e. the minicircle valence is 3). Replication involves the release of
      minicircles from the interior of the network, the synthesis of nicked or gapped
      progeny minicircles and the attachment of the progeny to the network periphery.
      The ultimate result is a Form II network of 10,000 nicked or gapped minicircles.
      Our measurements of minicircle valence and density, and the network's surface
      area, revealed striking changes in network topology during replication. During
      the S phase, the peripheral newly replicated minicircles have a density twice
      that of minicircles in Form I networks, which suggests that the valence might be
      as high as 6. Most of the holes in the central region that occur from the removal
      of intact minicircles are repaired so that the central density and valence remain
      the same, as in prereplicative networks. When minicircle replication is complete
      at the end of the S phase, the isolated network has the surface area of a
      prereplicative network, despite having twice the number of minicircles. During
      the G2 phase, the Form II network undergoes a remodeling in which the area
      doubles and the valence is reduced to 3. Finally, the interruptions in the
      minicircles are repaired and the double-sized network splits in two.

PMID- 8557056
TI  - 1995 Mack-Forster Award Lecture. Review. Mast cell differentiation antigens:
      expression in normal and malignant cells and use for diagnostic purposes.
AB  - Antibodies against haemopoietic differentiation antigens are widely used for the
      identification and classification of leukaemic cells. Mast cells are distinct
      haemopoietic cells and express a unique composition of antigens. They can be
      differentiated from basophils and all other lymphohaemopoietic cells by using
      antibodies to cell surface receptors and granular mediator molecules. This paper
      provides evidence that antibodies against mast cell antigens can be used to
      identify and classify malignant cell populations in patients with mastocytosis.

PMID- 8557055
TI  - Genetic analysis of an ARS element from the fission yeast Schizosaccharomyces
      pombe.
AB  - ARS (autonomously replicating sequence) elements are DNA fragments that can
      function as origins of DNA replication in yeast. We report the first fine
      structure analysis of ars1, an ARS element of the fission yeast
      Schizosaccharomyces pombe. Characterization of a series of nested deletion
      mutations indicated that the minimal fragment of DNA encompassing ars1 is
      surprisingly large. No fragment < 650 bp retained significant ARS activity.
      Analysis of deletion and substitution mutations scanning the entire minimal ars1
      identified a single essential 50 bp fragment (segment 1). Only one other 50 bp
      mutation reduced activity as much as 5-fold and most deletions were without
      effect. Thus, the minimal ars1 is composed of two general types of genetic
      elements, a small segment that is absolutely required for efficient ARS activity
      and a much larger region that is tolerant of internal structural alterations.
      Higher resolution analysis of segment 1 defined a critical 30 bp A/T-rich segment
      which appears to contain redundant genetic elements. Schizosaccharomyces pombe
      ars1 promoted high frequency transformation in the budding yeast S.cerevisiae but
      this heterologous activity was not dependent on segment 1. Our analysis indicates
      that the functional elements required for ARS function in S.pombe and
      S.cerevisiae are clearly different.

PMID- 8557057
TI  - The use of ferric nitrilotriacetate and ferrozine in iron transport studies.

PMID- 8557058
TI  - Cellular mechanisms underlying the increased duodenal iron absorption in rats in
      response to phenylhydrazine-induced haemolytic anaemia.
AB  - Haemolytic anaemia induced by phenylhydrazine (PZ) promotes iron absorption
      across rat small intestine. This present study investigates the role of the brush
      border potential difference (Vm) and mucosal reducing activity in the response.
      In addition, quantitative autoradiography was used to assess PZ-induced changes
      in the villus localization of brush border iron uptake. Iron transfer from
      duodenum to blood was increased significantly 5 days after treatment with PZ.
      Autoradiography showed that most brush border iron uptake occurred at the upper
      villus region and the maximal rate was increased fourfold by PZ. Duodenal villus
      length was increased in PZ-treated rats. PZ treatment did not influence mucosal
      reducing activity but Vm, measured using duodenal sheets, increased from -50 to 
      57 mV (P < 0.001) and this was due to a reduced brush border sodium permeability.
      Thus, an expanded absorptive surface and an enhanced electrical driving force for
      iron uptake across the duodenal brush border are important adaptations for
      increased iron absorption in PZ-induced haemolytic anaemia.

PMID- 8557059
TI  - Urodilatin (ularitide, INN): a potent bronchodilator in asthmatic subjects.
AB  - Atrial natriuretic peptide (CDD/ANP-99-126) has been identified as a
      bronchodilator in various species including humans. We investigated the effect of
      urodilatin (CDD/ANP-95-126) in 18 clinically stable asthmatics showing an
      increase of the FEV1 by > or = 15% after salbutamol inhalation. Prior to the
      study inhaled beta 2-agonists were withheld for 8 h. After baseline measurements
      of lung function parameters (FEV1, VC, PEF, MEF75, MEF50, MEF25), blood pressure,
      and heart rate in intravenous infusion of 20, 40 or 60 ng kg-1 min-1 urodilatin
      was administered for 40 min in the morning. All measurements were repeated every
      10 min during the infusion, for 30 min thereafter, and after the inhalation of
      1.25 mg salbutamol. Forty and 60 ng kg-1 min-1 urodilatin showed a significant
      effect on the central (FEV1, PEF, MEF75) and peripheral airways (MEF50, MEF25)
      after 10 min infusion (P < 0.05). A bronchodilation not significantly different
      from 1.25 mg salbutamol was induced by 40 ng kg-1 min-1 in the central airways
      only, while 60 ng kg-1 min-1 led to a similar effect at all levels of the
      bronchial tree. Lung function parameters returned to baseline within 30 min after
      cessation of the urodilatin infusion. Heart rate showed a tendency to increase
      after 40 min infusion (P < 0.05), but blood pressure did not change
      significantly. In conclusion, the maximal bronchodilating effect of intravenous
      urodilatin in clinically stable asthmatics was comparable to 1.25 mg salbutamol.

PMID- 8557060
TI  - Human endothelial cells bioactivate organic nitrates to nitric oxide:
      implications for the reinforcement of endothelial defence mechanisms.
AB  - Although in therapeutic use for more than a century, the mode of cellular action
      of organic nitrates remains incompletely understood. Despite ample experimental
      evidence from animal studies to show that nitrates are metabolized to NO in the
      vascular smooth muscle, direct demonstration of such an activity in human
      vascular cells is still lacking. Moreover, the role of the endothelium in
      modulating the pharmacodynamic action of nitrates is far from clear. We therefore
      aimed to investigate whether or not human endothelial cells are capable of
      bioactivating these drugs to NO and whether the amounts generated are sufficient
      to elicit any biological effects. Using cultured human umbilical vein endothelial
      cells (HUVECs) as an established model system a combination of three different
      methods was used to address this issue: (1) quantification of NO formation upon
      endothelial nitrate metabolism using the oxyhaemoglobin technique; (2) evaluation
      of the second messenger response using radioimmunoassay for cGMP; and (3)
      assessment of mechanism and extent of potentiation of the anti-aggregatory effect
      of nitrates in the presence of endothelial cells as a relevant bioassay. We now
      show that superfusion of cultured human endothelial cells on microcarrier beads
      with either glyceryl trinitrate (GTN) or isosorbide dinitrate (ISDN; both at 0.1
      100 mumol L-1) results in a concentration-dependent formation of NO. NO
      generation from isosorbide 5-mononitrate (IS-5-N) was below the detection limit.
      The amounts of NO produced (maximally 2.97 +/- 0.98 pmoles NO min-1 x mg protein
      with 100 mumol L-1 GTN; n = 8) were similar to those elicited upon challenge of
      the cells with 100 nM bradykinin. NO formation from either organic nitrate was
      accompanied, in a concentration-dependent and methylene blue-inhibitable manner,
      by stimulation of endothelial soluble guanylyl cyclase with consequent increases
      in the intracellular level of cGMP (maximally 32-fold over basal levels with
      ISDN), a significant portion of which was released into the extracellular space.
      Upon continuous 30 min superfusion or repeated application of high concentrations
      of GTN (100 mumol L-1) nitrate bioactivation to NO was subject to partial
      tachyphylaxis. Co-incubation of washed human platelets with HUVECs potentiated
      the anti-aggregatory action of nitrates in a cell number dependent and
      oxyhaemoglobin-sensitive manner and this effect, too, was accompanied by
      increases in intraplatelet cGMP levels. The potentiating effect was largely
      inhibited after blockade of sulfhydryl groups by pre-incubation of HUVECs with N
      ethylmaleimide and completely abrogated after pretreatment of cells with the
      tissue fixative glutaraldehyde. These results demonstrate that human endothelial
      cells are capable of bioactivating organic nitrates to NO by an enzymatic,
      apparently thiol-sensitive pathway, in quantities sufficient to influence
      endothelial and platelet function. Besides the well known vasorelaxant action of
      organic nitrates, which is mainly due to their metabolism in the smooth muscle
      compartment, these drugs may therefore be endowed with a hitherto underestimated
      potential to directly influence endothelial functions via the NO/cGMP pathway.
      Through specific bioactivation in the endothelium itself organic nitrates can
      thus mimic and reinforce protective functions normally served by a functional
      endothelium such as the modulation of blood cell/vessel wall interactions and
      inhibition of cell proliferation.

PMID- 8557061
TI  - Effects of cholestyramine on gallbladder and gastric emptying in obese and lean
      subjects.
AB  - Gallbladder stasis is frequent in obese subjects and may contribute to their
      increased risk for gallstone formation. The bile salt sequestrant cholestyramine
      acutely enhances postprandial gallbladder emptying in lean subjects, through
      disinhibition of a negative feedback between intraluminal bile salts and CCK
      release. In this study the effect of cholestyramine on both gallbladder and
      gastric antrum dynamics were studied by real-time ultrasonography in 12 obese and
      15 lean subjects. For the acute study, on different days, subjects ingested a
      liquid meal (two egg yolks plus water 200 mL, 50 kJ) or a meal with 4 g
      cholestyramine. Gallbladder emptying was impaired in obese patients who had
      significantly larger fasting gallbladder volume (39.4 +/- 6.9 vs. 21.6 +/- 1.7
      mL, P < 0.02), larger residual volume (12.3 +/- 1.8 vs. 4.0 +/- 0.5 ml, P <
      0.0006) and slower emptying time (T/2: 33 +/- 2 vs. 21 +/- 2 min, P < 0.05) than
      lean subjects. Integrated antral emptying was also less in obese than lean
      subjects (5521 +/- 578 vs. 7908 +/- 491 %120 min-1, P < 0.02). Cholestyramine
      enhanced postprandial gallbladder emptying in both obese and lean subjects.
      Gastric emptying was delayed with cholestyramine in lean but not obese subjects.
      For the chronic study, after 1 month therapy with cholestyramine (4 g every 2
      days), the motility tests were repeated in nine obese subjects. Gallbladder and
      gastric responses to a test meal, with or without cholestyramine, were preserved.
      We conclude that both gallbladder and antral emptying of a liquid test meal are
      impaired in obese subjects. Gallbladder emptying improves after acute
      administration of a low dose cholestyramine with test meal. This effect is
      sustained after 1 month treatment with a low dose of cholestyramine and does not
      interfere with gastric emptying of obese patients. Cholestyramine may improve
      gallbladder hypomotility in obese people.

PMID- 8557062
TI  - Neurohumoral antecedents of vasodepressor reactions.
AB  - Vasodepressor (vasovagal) syncope, the most common cause of acute loss of
      consciousness, can occur in otherwise vigorously healthy people during exposure
      to stimuli decreasing cardiac filling. Antecedent physiological or neuroendocrine
      conditions for this dramatic syndrome are poorly understood. This study compared
      neurocirculatory responses to non-hypotensive lower body negative pressure (LBNP)
      in subjects who subsequently developed vasodepressor reactions during hypotensive
      LBNP with responses in subjects who did not. In 26 healthy subjects, LBNP at -15
      and -40 mmHg was applied to inhibit cardiopulmonary and arterial baroreceptors.
      All the subjects tolerated 30 min of LBNP at -15 mmHg, but during subsequent LBNP
      at -40 mmHg 11 subjects had vasodepressor reactions, with sudden hypotension,
      nausea, and dizziness. In these subjects, arterial plasma adrenaline responses to
      LBNP both at -15 and at -40 mmHg exceeded those in subjects who did not
      experience these reactions. In 16 of the 26 subjects, forearm noradrenaline
      spillover was measured; in the eight subjects with a vasodepressor reaction, mean
      forearm noradrenaline spillover failed to increase during LBNP at -15 mmHg (delta
      = -0.06 +/- (SEM) 0.04 pmol min-1 100mL-1), whereas in the eight subjects without
      a vasodepressor reaction, mean forearm noradrenaline spillover increased
      significantly (delta = 0.31 +/- 0.13 pmol min-1 100mL-1). Plasma levels of beta
      endorphin during LBNP at -15 mmHg increased in some subjects who subsequently had
      a vasodepressor reaction during LBNP at -40mmHg. The findings suggest that a
      neuroendocrine pattern including adrenomedullary stimulation, skeletal
      sympathoinhibition, and release of endogenous opioids can precede vasodepressor
      syncope.

PMID- 8557063
TI  - Red blood cell cation transports in uraemic anaemia: evidence for an increased
      K/Cl co-transport activity. Effects of dialysis and erythropoietin treatment.
AB  - This study examines the role of uraemia and the effect of different dialysis
      treatments on red cell cation transport. We evaluated the main cation transport
      systems in erythrocytes of non-dialysed end-stage renal disease (ESRD) subjects,
      of patients undergoing haemodialysis (HD) and continuous ambulatory peritoneal
      dialysis (CAPD), as well as the changes induced by human recombinant
      erythropoietin (r-HuEPO) administration. In uraemic undialysed and dialysed
      patients, we observed an increase in K/Cl co-transport activity and in shrinkage
      induced amiloride-sensitive (HMA-sensitive) Na efflux (Na/H exchange) and a
      decrease in Na/K pump and Na/K/Cl co-transport activity, while Na/Li exchange was
      increased only in dialysed patients. In uraemic erythrocytes, we showed for the
      first time an increased K/Cl co-transport activity, which was cell age
      independent. Generally, the different method of dialysis (CAPD or HD) did not
      modify the cation transport abnormalities observed. During the treatment with r
      HuEPO, all the systems, with the exception of the Na/K pump and Na/K/Cl co
      transport, increased their activities following the increase of circulating young
      red cells. The changes produced under r-HuEPO administration were transient and
      cation transports returned to the baseline values within 100 days of treatment,
      indicating a primary and prominent pathogenetic role of uraemia in modulating the
      red cell membrane cation transport activities.

PMID- 8557064
TI  - Studies in hypertriglyceridaemia, III: Glucose tolerance, insulin sensitivity and
      indices of adipose tissue lipolysis in randomly selected non-diabetic
      hypertriglyceridaemic Swedish men.
AB  - Hypertriglyceridaemia, insulin resistance and glucose intolerance are conditions
      associated with an increased risk of coronary heart disease. In this study we
      have examined randomly selected nondiabetic hypertriglyceridaemic (HTG) males, 40
      50 years (n = 65) and age-matched normotriglyceridaemic (NTG) controls (n = 61).
      The (mean +/- SD) insulin sensitivity index, as assessed by the Minimal Model
      method, was significantly lower in the HTG compared with the NTG group (3.69 +/-
      2.96 vs. 6.29 +/- 3.38 x 10(-4) min-1 per mUL-1; P < 0.001). Thirty-eight per
      cent of the HTG group was glucose intolerant, compared with 8% in the NTG group
      (X2 = 13.16; P < 0.001). The glucose intolerant HTG sub-group had, when compared
      with the glucose tolerant one, significantly higher serum concentrations of apoB
      (1318 +/- 284 vs. 1094 +/- 312 mg L-1; P < 0.01) and glycerol (84 +/- 26 vs. 65
      +/- 22 nmol L-1; P < 0.01). Serum FFA concentrations were, irrespective of
      glucose tolerance/intolerance, higher in the HTG than in the NTG group. By
      logistic regression analysis with the HTG/NTG state as the dichotomous variable,
      it was found that neither a low insulin sensitivity, nor glucose intolerance were
      independently linked with the HTG state. Instead, the lower insulin sensitivity
      of the HTG group was related to their higher body mass index. The higher
      frequency of glucose intolerance in the HTG group was explained by their higher
      mean serum apoB concentration, when compared with the NTG group. In conclusion,
      this study of a randomly selected of HTG group has confirmed the frequent
      coexistance of HTG, insulin resistance and glucose intolerance. The new important
      finding was that neither of these two latter conditions appear to be of direct
      pathogenetic importance for HTG.

PMID- 8557065
TI  - Peroxides in human leucocytes in acute septic shock: a preliminary study of acute
      phase changes and mortality.
AB  - Peroxidation by peripheral blood leucocytes was measured in 15 patients in acute
      septic shock and 15 uninfected controls, using the probe dichloroflorescein.
      Mortality in septic subjects was 40%. In 14 of 15 patients from whom serial
      samples were analysed, periods of increased oxidative activity were detected.
      Increased peroxidation occurred early in the sequence of clinical changes, at the
      same time as increases in temperature, blood pressure and C-reactive protein.
      Peak peroxide production preceded increases in acute phase reactants and changes
      in leucocyte distribution. Mean peroxide production in leukocytes from patients
      who died was significantly higher (P < 0.001) than paired controls, and greater
      (P < 0.05) than peroxide production in patients who survived. The in vitro
      oxidative response to endotoxin was upregulated in infected patients. This
      supports the hypothesis that systemic mediators and leucocyte-derived reactive
      oxygen are involved in the vascular and organ damage associated with fatal septic
      shock.

PMID- 8557067
TI  - Subcellular distribution of small GTP-binding proteins in the intestinal cell
      line Caco-2.
AB  - The present study describes the subcellular distribution of low molecular weight
      GTP-binding proteins in the human carcinoma cell line Caco-2. Highly enriched
      subcellular fractions of basolateral and brush border membranes were prepared by
      differential density centrifugation and divalent cation precipitation. Small
      molecular weight GTP-binding proteins were identified after SDS-PAGE transfer to
      nitrocellulose using [alpha 32P]-labelled GTP. Smg-proteins with molecular masses
      of 28, 27, 25 and 24 kDa were detectable in all fractions. Homogenate and brush
      border membrane fraction showed specific binding of [alpha 32P] GTP to proteins
      of a molecular mass of 21 kDa, while in the membrane fractions (apical,
      basolateral) a high enrichment of 24 kDa smg-proteins was detectable. Western
      blot analysis identified one of the 21 kDa proteins of the brush border membrane
      as rhoA. The homogenate of 4, 8, 11 and 14 days old Caco-2 cells showed different
      [alpha 32P]-GTP binding to 21, 27 and 28 kDa proteins. In conclusion, this study
      is the first showing the presence and asymmetrical distribution of smg-proteins
      among the various membrane components in the human carcinoma cell line Caco-2.

PMID- 8557066
TI  - The effect of recombinant human IGF-I on protein metabolism in post-operative
      patients without nutrition compared to effects in experimental animals.
AB  - This study has evaluated the effects of recombinant human insulin-like growth
      factor I (rhIGF-I) to moderately stressed post-operative patients provided with
      dextrose as the only exogeneous substrate. Thirty patients who underwent elective
      colorectal surgery were randomized to receive either rhIGF-I (80 micrograms kg-1
      bw) subcutaneously twice daily or placebo injections in a double-blind parallel
      group design. Nitrogen balance, urinary 3-methyl-histidine excretion plasma
      growth hormone (GH), serum cortisol, IGF-I binding proteins (IGFBP-1,3),
      glomerular filtration rate, plasma amino acid concentrations and whole-body
      energy expenditures were measured as effector variables during days 1-5 post
      operatively. Animal and isolated tissue experiments were performed as additional
      control experiments to confirm cellular effectiveness of the recombinant
      material. rhIGF-I increased significantly the glomerular filtration rate and
      prevented the adaptive decrease in whole-body energy expenditure in response to
      partial starvation in the postoperative period. Serum and plasma concentrations
      of IGFBP-1,3 cortisol, blood glucose and amino acids were not significantly
      influenced by rhIGF-I administration, while plasma GH levels decreased
      significantly as expected. rhIGF-I had no effect on either nitrogen balance or
      protein breakdown (3-methylhistidine excretion) in post-operative patients on
      dextrose supplementation only, although plasma concentrations of IGF-I increased
      from 130-140 ng mL-1 to a range of 300-450 ng mL-1. In contrast, IGF-I stimulated
      the synthesis of both globular and myofibrillar proteins (+50%, P < 0.01), when
      given as a single dose (100 micrograms kg-1) 2 h before measurements of protein
      synthesis in skeletal muscles of overnight fasted adult mice. This stimulatory
      effect by IGF-I (1 microgram mL-1) was also confirmed by measurements of skeletal
      muscle protein synthesis in vitro (+40%, P < 0.05). Orally re-fed mice had a
      normal transcription of IGF-I mRNA in skeletal muscle cells, while overnight
      fasted mice showed a trend to down-regulated transcription. Our results
      demonstrate that rhIGF-I has several significant physiological effects, without
      major side-effects, when supplied to partially starved patients in the post
      operative phase. The lack of a whole-body nitrogen sparing effect by rhIGF-I
      alone to post-operative patients is not clear, but was most likely explained by
      subnormal plasma concentrations of amino acids.

PMID- 8557068
TI  - Free amino acid concentrations in normal and abnormal third trimester placental
      villi.
AB  - Homogenates of placental villi were obtained from normotensive pregnancies and
      from pregnancies complicated by pre-eclampsia and growth retardation. The
      homogenates were analysed for free amino acid concentrations using high
      performance liquid chromatography (HPLC). The study shows that there are
      significantly higher concentrations of two essential amino acids, L-arginine and
      phenylalanine (P < 0.05), in the growth-retarded group compared to the term
      normotensive and pre-eclamptic groups. There are significantly higher
      concentrations of the non-essential amino acids: glutamic acid in the growth
      retarded group compared to the normotensive group, and of tyrosine in the growth
      retarded group compared to the pre-eclamptic group. However, there is no increase
      in the glycine/valine ratio, a characteristic marker for kwashiorkor or a
      reduction in total protein concentration in the pre-eclamptic or growth-retarded
      groups. These findings suggest that there may be abnormalities in placental
      metabolism, amino acid transfer across the basal membrane into the fetal
      circulation, and also fetoplacental perfusion in pregnancies complicated by pre
      eclampsia and growth retardation.

PMID- 8557069
TI  - Virology research and virulent human pandemics.
AB  - The possibility that a devastating human pandemic could arise, causing massive
      loss of human life, is discussed. Such a major threat to the human species is
      likely to be a virus, and would spread by the respiratory route. It need not
      necessarily cause massive loss of life, but if it caused serious illness or
      incapacity it would still have a major impact. A possible source is from an
      existing respiratory pathogen, but it would more probably arise from an infection
      that is maintained in an arthropod or vertebrate host, but which at present
      either does not infect humans, or if it does it fails to be effectively
      transmitted between them. More research should therefore focus on the
      pathogenetic factors and the viral determinants that promote respiratory
      transmission.

PMID- 8557070
TI  - A cluster of cases of streptococcal necrotizing fasciitis in Gloucestershire.
AB  - We describe the first cluster of cases of necrotizing fasciitis (NF) in this
      century in the United Kingdom (UK). Between 1 January and 30 June 1994 there were
      six cases (five confirmed, one probable) of Streptococcus pyogenes NF in west
      Gloucestershire, population 320,000. Two cases died. The first two patients
      probably acquired their infections during the course of elective surgery
      performed in the same operating theatre, possibly from a nasopharyngeal carrier
      amongst the theatre staff. The remaining infections were community-acquired. Of 5
      S. pyogenes isolates there were 2 M1 strains, 1 M3, 1 M5 and 1 M non-typeable
      strain. S. pyogenes NF had not been recorded in west Gloucestershire in the
      preceding 10 years and the incidence of S. pyogenes bacteraemia in England and
      Wales had not risen in the past 5 years. The two presumably theatre-acquired
      infections raised several issues. The need for detailed bacteriological
      investigation of all cases of post-surgical NF was confirmed. Clusters of S.
      pyogenes infection following surgery should be managed by closure of the
      operating theatre until all staff have been screened for carriage. Closure of an
      operating theatre and screening of staff following a sporadic case is probably
      not justified because of the infrequency of surgical cross-infection with S.
      pyogenes. Regular, routine screening of theatre staff is neither practical nor
      necessary.

PMID- 8557071
TI  - Epidemiological investigation of an outbreak of meningococcal meningitis in
      Makkah (Mecca), Saudi Arabia, 1992.
AB  - During March and April of 1992, the health surveillance system began detecting
      increasing numbers of cases of meningococcal disease (MCD) in the Islamic holy
      city of Makkah (Mecca). We identified 102 bacteriologically confirmed cases (CC)
      and 80 suspected cases (SC) of MCD. Neisseria meningitidis was identified as
      Group A, III-1 clone. The ratio of male:female cases was 2.9:1. All age groups of
      males were affected. There was only one case among women aged 10-30; 50% of the
      adult female cases were 55 or older. The case-fatality ratio (CFR) was 14.7%
      among CC. Pakistanis, who comprised about one-third of the CC, had a CFR of
      26.7%. Fifty-nine percent of CC were religious visitors. CC in residents were
      most common in persons living near the Holy Mosque (Haram), where the carriage
      rate reached 86%. A mass vaccination program against MCD was instituted, using AC
      bivalent meningococcal vaccine (MCV). An abrupt drop, from a mean of 15 CC per
      week to 2 CC per week (only in visitors), coincided with vaccinating 600,000
      persons over 2 weeks. Makkah residents who had been vaccinated against MCD were
      less likely to have contracted MCD (OR = 0.17, 95% CI: 0.06-0.50). MCV was of no
      significant protective value if it had been administered 5 years before the
      outbreak. The main reason for not being vaccinated as stated by both cases (71%)
      and controls (45%) was not knowing about the disease. The age and sex differences
      probably relate to differences in exposures to crowded conditions. Health
      education should illuminate the seriousness of the disease and the importance of
      vaccination.

PMID- 8557072
TI  - Targeted vaccination with meningococcal polysaccharide vaccine in one district of
      the Czech Republic.
AB  - Vaccination against Neisseria meningitidis is not part of routine immunization
      schemes in any country; instead, targeted vaccination of groups at the highest
      risk is recommended during outbreaks and epidemics. After a long period of
      sporadic occurrence of meningococcal invasive disease, a new clone of Neisseria
      meningitidis C:2a:P1.2, ET-15/37, occurred in the Czech Republic, and caused
      local outbreaks in two neighbouring districts, Olomouc and Bruntal, in spring
      1993. In Olomouc, a mass campaign was conducted during which 6191 students were
      vaccinated (5.6% of the total population of this locality and 96% of all students
      in the age group 15-19) within 2 weeks in June 1993. In Bruntal district, no such
      campaign was organized. In Olomouc, the incidence of invasive disease caused by
      Neisseria meningitidis C in the age group 10-24 decreased from 57 to 0 per
      100,000 (P < 0.001) during the post-vaccination period (July 1993-August 1994),
      but no such decrease was observed in Bruntal. Although other factors can affect
      the frequency of disease, these results support the current recommendations of
      targeted vaccination in outbreaks of meningococcal disease.

PMID- 8557073
TI  - Analysis of methicillin-resistant and methicillin-susceptible Staphylococcus
      aureus by a molecular typing method based on coagulase gene polymorphisms.
AB  - A molecular typing method for Staphylococcus aureus based on coagulase gene
      polymorphisms (coagulase gene typing) was evaluated by examining a total of 240
      isolates which comprised 210 methicillin-resistant S. aureus (MRSA) and 30
      methicillin-susceptible S. aureus (MSSA) collected from a single hospital. By
      AluI restriction enzyme digestion of the PCR-amplified 3'-end region of the
      coagulase gene including 81-bp repeated units, the MRSA and MSSA isolates
      examined were divided into 6 and 12 restriction fragment length polymorphism
      (RFLP) patterns, respectively, whereas five patterns were commonly detected in
      MRSA and MSSA. MRSA isolates that showed a particular RFLP pattern were
      considered to be predominant in the hospital. Coagulase typing with type-specific
      antisera was also performed for all S. aureus isolates for comparison. Coagulase
      types II and VII were most frequently detected and included isolates with four
      and five different AluI RFLP patterns, respectively, whereas each of the other
      coagulase types corresponded to a single RFLP pattern. These results indicated
      that RFLP typing was more discriminatory than serological typing, for typing S.
      aureus and demonstrated its utility in epidemiologic investigation of S. aureus
      infection in hospitals.

PMID- 8557074
TI  - Biotype traits and antibiotic susceptibility of Vibrio cholerae serogroup O1
      before, during and after the emergence of the O139 serogroup.
AB  - Sixty-nine strains of Vibrio cholerae O1 isolated at different times were
      analysed to investigate if there were any differences among the O1 strains
      isolated before, during and after the advent of the O139 serogroup. Of the 69 O1
      strains examined, 68 belonged to the Ogawa serotype while one belonged to the
      Inaba serotype. With the exception of one strain all other strains of V. cholerae
      O1 belonged to the eltor biotype. A single O1 strain isolated before the
      emergence of the O139 serogroup could not be classified as either eltor or
      classical biotype because it was resistant to both classical and eltor specific
      bacteriophages. Marked variations in the susceptibility to antibiotics of V.
      cholerae O1 isolated during the different periods were observed. In addition,
      strains of V. cholerae isolated after the epidemic of serogroup O139 in Calcutta
      showed an expanding R-type with resistance to a variety of drugs as compared to
      the O1 strains isolated before the advent of the O139 serogroup. From this study,
      it is clear that there is a substantial mobility in genetic elements of V.
      cholerae O1 which necessitates a continuous monitoring to keep abreast of the
      changing traits of the etiologic agent of cholera.

PMID- 8557075
TI  - An epidemiological study of Vibrio cholerae O1 in the Australian environment
      based on rRNA gene polymorphisms.
AB  - Since 1977, Vibrio cholerae O1 has been isolated from the Australian aquatic
      environment and periodically cholera cases have occurred following exposure to
      these environments. To study the relationships between clinical isolates and
      environmental isolates from rivers and aquatic life, widely distributed
      throughout the country, a wide range of molecular typing methods were employed.
      In this paper we report the analysis of the 180 Australian isolates (10 clinical
      and 170 environmental) using ribotyping. Seven ribotype patterns were observed
      among the Australian inaba isolates, 2 of which included all clinical inaba
      isolates and 84% environmental inaba isolates collected from 9 rivers and creeks
      in eastern Australia during an 8-year period. Isolates from epidemiologically
      related clinical cases, asymptomatic household contacts and sewage were
      indistinguishable. The ogawa isolates were more diverse, with 9 ribotypes
      observed among 24 isolates from 8 rivers during the same period. Ribotype
      patterns were not shared between the serotypes with the exception of one ogawa
      isolate which could be distinguished using PFGE. Ribotyping has been useful in
      confirming an association between epidemiologically related clinical isolates and
      the aquatic environment and the persistence of several clones of the O1 serovar
      in the Australian environment during an 8-year period.

PMID- 8557076
TI  - The role of heightened surveillance in an outbreak of Escherichia coli O157.H7.
AB  - After instituting laboratory screening for Escherichia coli O157.H7, a
      Connecticut hospital isolated the organism from four persons in September 1993.
      As a result, an outbreak of E. coli O157.H7 associated with a country club was
      detected. The club had served hamburger from the same shipment at two picnics.
      Attendees of two picnics were interviewed, stool cultures were obtained from
      symptomatic persons, and the remaining hamburger was cultured. Twenty (22%) of 89
      persons who ate hamburger became ill, compared with 1 of 60 who did not eat
      hamburger (relative risk = 13.5, 95% confidence interval 3.2-56.3). Among persons
      who ate hamburgers, illness was strongly associated with eating hamburger that
      was not thoroughly cooked (P < 0.001). All 20 samples from 5 remaining boxes of
      patties yielded E. coli O157.H7. Isolates from hamburger and case-patients were
      indistinguishable by pulsed-field gel electrophoresis. Heightened surveillance
      can rapidly identify outbreaks and may mitigate their impact. However, continued
      review of food safety issues is necessary if E. coli O157.H7 outbreaks are to be
      prevented.

PMID- 8557077
TI  - Isolation of enterotoxigenic Escherichia coli from British troops in Saudi
      Arabia.
AB  - Specimens from 181 patients with diarrhoea were examined by a Military General
      Hospital in a 3-month period during deployment of troops to Saudi Arabia in
      1990/1. DNA probes for heat labile (LT) and heat stable (ST) enterotoxin genes
      identified enterotoxigenic Escherichia coli (ETEC) in 47 of the specimens (26%)
      and 49 ETEC strains were isolated. The majority (55%) belonged to a novel ETEC
      serotype having the O-antigen 159 and a flagellar antigen designated as a
      provisional new type. They produced ST and the coli surface associated antigen
      (CS)6. Strains of serotype O6:H16 represented 22% of the ETEC examined. They
      produced ST, LT and CS3 together with either CS1 or CS2. The remaining ETEC
      belonged to seven O:H serotypes. Overall, ST was the only enterotoxin gene
      identified in 73% of the ETEC and 67% of the strains expressed CS6 in the absence
      of other colonization antigens. Resistance to three or more antibiotics was
      observed in 53% of the ETEC, including most of the O159 strains.

PMID- 8557078
TI  - Adhesion of Aeromonas sp. to cell lines used as models for intestinal adhesion.
AB  - Adhesion to HEp-2 cells has been shown to correlate with enteropathogenicity for
      Aeromonas species. Such adhesion is thought to reflect the ability of strains to
      adhere to human intestinal enterocytes, although HEp-2 cells are not of
      intestinal origin. In this study strains of Aeromonas veronii biotype sobria
      isolated from various sources were investigated in parallel assays for their
      ability to adhere to HEp-2 cells and to an intestinal cell line (Caco-2).
      Quantitative assays showed identical adhesion values were obtained with both cell
      lines. Adhesion was best when bacteria were grown at 22 degrees C compared with
      37 degrees C and 7 degrees C. Some environmental isolates showed greater adhesion
      when grown at 7 degrees C than when grown at 37 degrees C. Filamentous structures
      on these strains are also optimally expressed under the above conditions
      (reported elsewhere). Mechanical shearing or trypsin treatment to remove surface
      structures from several adhesive strains grown at 22 degrees C decreased adhesion
      to cell lines by 50-80% providing further indirect evidence that filamentous
      adhesins may play a role in cell adhesion for this Aeromonas species.

PMID- 8557079
TI  - Antibiotic susceptibility of campylobacter isolates from sewage and poultry
      abattoir drain water.
AB  - In this study, the in vitro susceptibility of 209 campylobacter strains to the
      quinolones nalidixic acid, flumequine, ciprofloxacin, enrofloxacin, and to
      ampicillin, tetracycline and erythromycin was tested by the disk diffusion
      method. The strains were isolated from poultry abattoir effluent (DWA) and two
      sewage purification plants (SPA and SPB). Sewage purification plant SPA received
      mixed sewage, including that from a poultry abattoir, whereas SPB did not receive
      sewage from any meat-processing industry. The quinolone resistance of the DWA
      isolates ranged from 28% for enrofloxacin to 50% for nalidixic acid. The strains
      isolated from the sewage purification plants were more susceptible to the
      quinolones with a range of 11-18% quinolone resistance for SPB isolates to 17-33%
      quinolone resistance for SPA isolates. The susceptibility criteria as recommended
      by National Committee Clinical Laboratory Standards (USA) cannot readily be
      employed for campylobacter isolates. This investigation shows that the resistance
      of campylobacter bacteria is highest in the plant receiving sewage from a poultry
      slaughterhouse. Monitoring of antibiotic resistance of aquatic Campylobacter spp.
      is important, as surface waters are recognized as possible sources of infection.

PMID- 8557080
TI  - The speciation and subtyping of campylobacter isolates from sewage plants and
      waste water from a connected poultry abattoir using molecular techniques.
AB  - In this study the distribution of phenotypes of campylobacter strains in sewage
      and surface waters was investigated by subtyping and by speciation of isolates
      from various aquatic environments. These environments included two municipal
      sewage plants (SPA and SPB) and waste water from a poultry abattoir (WWA). Both
      the sewage plants SPA and SPB collected domestic and industrial waste, and SPA
      received drain water from WWA. SPB received no waste water from any meat
      processing plant. The isolates were speciated by PCR and subtyped by PCR/RFLP
      based on the flagellin PCR products. From all three reservoirs, no Campylobacter
      lari was isolated, and approximately 80% of the isolates could be identified as
      C. jejuni and the rest belonged to the C. coli species. The PCR/RFLP typing
      technique has a high discrimination level and was reproducible between two
      separate laboratories. The 182 isolates tested yielded 22 distinct Dde I
      profiles. The results indicate that strains with profiles found in poultry are
      also detectable in waste water presumed to be solely from domestic and human
      sources. In addition some strains were unique to the known poultry-related
      sources, suggesting that avian-specific strains, non-pathogenic to man, may exist
      in the environment. In contrast some strains were unique to human waste
      indicating the potential importance of non-poultry sources of infection. No
      seasonality was observed in the profile distribution. So, at least in the
      Netherlands, it is unlikely that infections caused by contaminated surface waters
      contribute to the seasonality of human campylobacteriosis.

PMID- 8557081
TI  - Effect of changes in processing to improve hygiene control on contamination of
      poultry carcasses with campylobacter.
AB  - Examination of neck skin and caecal samples taken at a commercial processing
      plant from 15 randomly chosen poultry flocks showed that all flocks were
      contaminated initially with thermophilic Campylobacter spp., even in the apparent
      absence of caecal carriage. During processing, numbers of campylobacter on skin
      samples were reduced by between 10 and 1000-fold. To improve hygiene control
      generally, chlorinated-water sprays were used to limit microbial contamination on
      equipment and working surfaces. In addition, chlorine concentrations in process
      water were increased and any unnecessary carcass contact surfaces in the
      processing plant were removed. When comparing flocks before and after the
      changes, it was found that numbers of campylobacter on packaged carcasses were
      significantly lower after the changes had been made (P 0.001). In practice,
      however, the reduction would be likely to have little impact on consumer exposure
      to campylobacter infection.

PMID- 8557082
TI  - Nationwide outbreak of human salmonellosis in Germany due to contaminated paprika
      and paprika-powdered potato chips.
AB  - Between April and September 1993, a nationwide outbreak of salmonellosis occurred
      in Germany which was traced to contaminated paprika and paprika-powdered potato
      chips. Of the estimated 1000 cases, children below 14 years were principally
      affected. Levels of 0.04-0.45 organisms per gram were found in the snacks. The
      infective dose was estimated at 4-45 organisms with an attack rate of 1 in 10,000
      exposed persons. The unique feature of the outbreak was the variety of serovars
      involved. S. saintpaul, S. rubislaw and S. javiana were isolated during the same
      time period from paprika powder, spice mixtures, snacks and patients. Their
      clonal identity was confirmed by molecular typing methods. Furthermore,
      monophasic and non-motile strains of rare salmonella O-groups were isolated from
      both paprika products and patients. This is the largest documented outbreak due
      to contaminated spices which proved that even extremely low numbers of
      salmonellae adapted to the dry state were able to cause illness.

PMID- 8557083
TI  - Chaos under canvas: a Salmonella enteritidis PT 6B outbreak.
AB  - An outbreak of Salmonella enteritidis PT 6B food poisoning, the first reported of
      this recently described phage type, resulted in illness among 46 of 49 members of
      a camping group in North Wales, 33 of whom were hospitalized. Epidemiological
      evidence (P < 0.0001) indicated that a lemon meringue pie was the vehicle of
      infection. Fresh shell eggs, stored after purchase at ambient temperature, appear
      to be the most likely source of infection, with multiplication during preparation
      and subsequent storage of the pie a significant contributory factor. Campers may
      be at greater risk than others and should consider the use of cold boxes for the
      transport and storage of eggs, and avoid the preparation of lightly cooked egg
      products under these basic conditions.

PMID- 8557084
TI  - Occurrence of Listeria species in ready to eat foods.
AB  - Over 8000 ready to eat foods were examined for the presence of Listeria species.
      Overall, 5% of foods were found to contain these organisms. Higher occurrence was
      found in some foods such as chicken (11%) and fish (14%). Most of the Listeria
      species isolated were L. monocytogenes (49%) and L. innocua (36%) with lower
      numbers of other species. No seasonal pattern in the recovery of L. monocytogenes
      was found. Unsatisfactory or potentially hazardous levels of L. monocytogenes
      were found in 14 products (< 0.2%), mostly cooked meats. Undercooked chicken
      products appeared to present the greatest risk for the duration of this survey.
      The small number of samples which were potentially hazardous suggests that the
      risk to consumers is not high, and this is confirmed by the absence of clinical
      cases in the region during the period of study.

PMID- 8557085
TI  - Faecal contamination on children's hands and environmental surfaces in primary
      schools in Leeds.
AB  - Gastro-intestinal diseases continue to be a major health problem in primary
      schools in the UK. This study, which took place in 20 primary schools in the
      Leeds area, investigated the presence of faecal indicator bacteria on children's
      hands and environmental surfaces. Faecal streptococci were used as an indicator
      of faecal contamination. A handwashing knowledge score was developed for each
      child. Those children with good hygiene knowledge had less faecal contamination
      on their hands (relative risk: 1.4, 95% CI = 1.09-1.81, P = 0.005). Those schools
      with higher hand counts were more likely to have had a reported outbreak of
      gastroenteritis in the past. Values of the Townsend Deprivation Index, an
      indicator of deprivation, were compared with the hand results and those schools
      in high deprivation areas had higher hand counts. Of the swabs taken from
      surfaces in the toilet areas and classrooms, the carpets in the classrooms were
      the most frequently contaminated surfaces.

PMID- 8557086
TI  - Prevalence of antibodies against Entamoeba histolytica in Mexico measured by
      ELISA.
AB  - The prevalence of antibodies against Entamoeba histolytica was studied in the
      Mexican population using an immunoenzyme assay in solid phase (ELISA) and
      semiautomatic equipment. The antigen was a mixture of membrane proteins obtained
      by Triton X-100 extraction from an axenic culture of Entamoeba histolytica HM1
      IMSS. The method was standardized by comparing serum samples from amoebic liver
      abscess patients with healthy volunteers. From the 60,538 samples supplied by the
      National Seroepidemiology Survey, antibodies were found in 4.49% (4.32-4.65% at
      95% confidence limit). More significant titres occurred in the central region of
      the country. The ratio female to male was 1.25:1. The population living in
      metropolitan areas had probably been infected at a younger age than those living
      in the country. Important differences were found in the seroprevalence obtained
      by ELISA compared with a study which used indirect haemagglutination (IHA) in the
      same sample frame.

PMID- 8557087
TI  - An outbreak of cryptosporidiosis associated with a resort swimming pool.
AB  - An outbreak of cyptosporidiosis occurred in late April 1993 among resort hotel
      guests which was temporally associated with, but geographically distant from, a
      massive waterborne outbreak of cryptosporidiosis in Milwaukee, Wisconsin, that
      occurred in late March and early April of 1993. A case-control study was
      performed among groups with members who reported illness and among a systemic
      sample of groups who stayed at the resort hotel during the risk period. Of 120
      persons interviewed, 51 (43%) met the case definition. Swimming in the resort
      hotel's pool was significantly associated with case status (OR = 9.8; 95% Cl 3.4,
      29.7), as was consumption of ice from the hotel's ice machines (OR = 2.3; 95% Cl
      1.01, 5.2). When analysis was restricted only to laboratory-confirmed cases and
      controls, swimming pool use was the only risk factor significantly associated
      with illness (OR = 13.0; 95% Cl 2.6, 88.7). Following waterborne outbreaks of
      cryptosporidiosis associated with water supplies, swimming pools should be
      considered as possible ongoing sources for transmission regionally.

PMID- 8557088
TI  - Outbreak of cryptosporidiosis associated with a disinfected groundwater supply.
AB  - In an outbreak of cryptosporidiosis in Warrington, a town in North-West England,
      47 cases were recorded between November 1992 and February 1993, most within the
      first month. There was a strong statistical association between cases and
      residence in an area supplied from two groundwater sources. In a case-control
      study, a strong association between having drunk unboiled tap water from these
      sources, and a dose-response relationship were found. Oocysts were not detected
      in the water supply. During very heavy rainfall one source of water was found to
      drain surface water directly from a field containing livestock faeces, thereby
      bypassing natural sandstone filtration. Exceptionally heavy rainfall occurred at
      the probable time of infection. After withdrawal of the original water supply,
      the outbreak rapidly subsided. It was concluded that there was very strong
      evidence that this outbreak was waterborne. This, the second documented outbreak
      of cryptosporidiosis attributable to a groundwater supply, demonstrates that
      infection can be transmitted from a disinfected groundwater source despite
      apparently satisfactory treated water quality. We recommended that guidelines for
      protection of groundwater are implemented, raw groundwater should be routinely
      monitored for microbiological contamination, and the structure of all sources and
      waterworks should be assessed in risk surveys of water catchment areas.

PMID- 8557089
TI  - Inactivation of HIV-1 by chemical disinfectants: sodium hypochlorite.
AB  - The efficacy of sodium hypochlorite was assessed against human immunodeficiency
      virus type 1 suspended in low (8% v/v) or high (80% v/v) concentrations of serum
      or in a high (80%) concentration of blood. In the presence of 8% serum, 100
      p.p.m. available chlorine in the disinfectant test mixture inactivated 3.75 log
      TCID50 HIV/ml within 30 s. When the test mixture contained 80% serum, 500 p.p.m.
      available chlorine inactivated more than 4 log TCID50 HIV/ml in 1-2 min. Lower
      concentrations of available chlorine were unable to inactivate the virus
      completely. In the presence of 80% blood, 1000 p.p.m. available chlorine in the
      disinfectant test mixture was unable to inactivate 3.75 log TCID50 HIV/ml,
      although 2500 p.p.m. available chlorine was able to inactivate at least 1.5 log
      TCID50 HIV/ml. In all test mixtures, the chlorine rapidly became combined and
      thus less active. Our results emphasise the importance of cleaning prior to
      disinfection with sodium hypochlorite since it may prove to be ineffective in the
      presence of high levels of organic matter. In cases where prior cleaning is
      impossible, care must be taken to use the higher recommended concentration (a
      minimum of 10,000 p.p.m. available chlorine).

PMID- 8557090
TI  - Study of the effectiveness of influenza vaccination in the elderly in the
      epidemic of 1989-90 using a general practice database.
AB  - The effectiveness of influenza vaccination in preventing serious illness and
      death was determined in an elderly population during the influenza epidemic of
      was determined in an elderly population during the influenza epidemic of was
      determined in an elderly population during the influenza epidemic of 1989-90. A
      retrospective cohort study was carried out using computerized general
      practitioner records on nearly 10,000 patients aged 55 years and over. After
      adjustment for potential confounding factors, recent immunization was found to
      have a protective effect of 75% (95% confidence intervals: 21-92%) against death.
      Protection did not appear to vary with either age or the presence of underlying
      chronic disease. As the complications of influenza are most common in those with
      underlying chronic disease, the study findings are consistent with the
      recommended policy for the use of influenza vaccine in the UK. Further work is
      necessary to determine the cost-effectiveness of extending immunization to other
      groups.

PMID- 8557091
TI  - Analysis of influenza A virus reinfection in children in Japan during 1983-91.
AB  - The epidemiology of influenza A in Japan was studied during 1979-91 and viruses
      isolated from reinfections during 1983-91 were analysed. Of 2963 influenza
      viruses isolated from reinfections during 1983-91 were analysed. Of 2963
      influenza viruses isolated during this period, 922 and 1006 were influenza
      A(H1N1) and A(H3N2) viruses respectively; the others were influenza B viruses.
      Influenza A(H1N1) and A(H3N2) caused 5 and 6 epidemics respectively, most
      accompanied by antigenic drift. Seventeen reinfections with H1N1 and 17 with H3N2
      were detected during our study. The primary and reinfection strains isolated from
      7 H1N1 and 10 H3N2 cases were studied by haemagglutination-inhibition, and amino
      acid and nucleotide sequences of the HA1 region of the haemagglutinin. Most of
      the primary and reinfection strains were antigenically and genetically similar to
      the epidemic viruses circulating at that time. However, in 4 out of 10 cases of
      reinfection with influenza H3N2 virus, reinfection strains were genetically
      different from the epidemic viruses.

PMID- 8557092
TI  - Measles vaccination policy.
AB  - Where immunization campaigns locally eliminate measles, it will be important to
      identify the vaccination policy most likely to prevent future epidemics. The
      optimum age for vaccination depends on the rate of decline of maternal antibody,
      because the presence of antibody reduces vaccine efficacy. The first part of this
      paper contains a quantitative reappraisal of the data on antibody decline and
      seroconversion rates by age. The decline in maternal antibody protection follows
      delayed exponentials, with delays of 2-4 months, and subsequent half-lives of 1-2
      months. Using this result in an analytical mathematical model we find that the
      optimal age to administer a single dose of vaccine to children, which is
      independent of vaccine coverage, lies within the range 11-19 months. We also show
      that, where the optimal age cannot be met, it is better to err towards late
      rather than early vaccination. There are therefore two reasons why developing
      countries, which presently vaccinate during infancy because measles transmission
      rates are high should eventually switch to the second year of life. The possible
      gains from two-dose vaccination schedules are explored with respect to both
      coverage and efficacy. A two-dose schedule will be beneficial, in principle, only
      when there is a need to increase net vaccine efficacy, after coverage has been
      maximized with a one-dose schedule.

PMID- 8557093
TI  - Dementia and age at death.
AB  - The objective of this paper is to investigate changes in dementia mortality, as
      recorded on death certificates in Canada. Use is made of data available at
      Statistics Canada for the period 1990-1991. During this period there have been
      appreciable changes over time in the ages at death and in the percentage of death
      certificates that mention dementia. This increase in mortality associated with
      dementia can be explained, in large part, by an increased tendency for dementia
      to be listed as an underlying cause of death on the death certificate. Also, the
      median ages at death of persons in Canada for the period 1990-1991, for whom
      dementia is recorded as the underlying cause of death, are similar to or greater
      than the ages at death reported for all other causes of death but excluding
      dementia. Because those who have dementia are living longer, there is an increase
      in the number of people with dementia (prevalence of dementia); this has
      important implications concerning public policy on health and aging. We discuss
      the significance of these changes with respect to the future prevalence of
      dementia.

PMID- 8557094
TI  - Circadian temperature rhythms of older people.
AB  - This collection of studies had the aim of exploring whether older (77+ years) men
      and women have circadian body temperature rhythms different from those of younger
      adults. A total of 20 older men and 28 older women were compared with either 22
      young men or 14 middle-aged men in four protocols; all but the first protocol
      using a subset of the sample. The four protocols were: 1) 24 h, and 2) 72 h data
      collections on a normal laboratory routine (sleeping at night); 3) between 36 h
      and 153 h of field data collection at home; and 4) 36 h of a constant conditions
      routine (wakeful bedrest under temporal isolation) in the laboratory. There was
      some evidence for an age-related phase advance in temperature rhythm, especially
      for the older men on a normal routine, though this was not present in the
      constant conditions protocol, where 5 of the older subjects showed major delays
      in the timing of the body temperature trough (10:00 or later). There was no
      statistically significant evidence from any of the protocols that older subjects
      generally had lower temperature rhythm amplitudes than younger adults. Only when
      older men were compared with younger men in 24-h rhythm amplitude by simple t
      test did any comparison involving amplitude achieve statistical significance (p <
      0.05).

PMID- 8557095
TI  - Life span prediction from the rate of age-related DNA demethylation in normal and
      cancer cell lines.
AB  - A method has been proposed for the Hayflick Limit prediction by the analysis of
      the 5-methylcytosine content in DNA at earlier and later cell passages. The
      following facts were used as the basis of the method: (i) the rate of m5C loss
      from DNA remains approximately constant during cell divisions and it does not
      depend on the cell donor age; (ii) this rate is inversely proportional to the
      Hayflick Limit as well as to the life span of cell donor species; (iii) the
      period corresponded to loss of all m5C residues from the genome coincides with or
      somewhat exceeds the Hayflick Limit of normal cells. The prognosis of the
      Hayflick Limit has usually been found in good agreement with the experimental
      evidences for various human, hamster, and mouse cell lines. The method proposed
      may be used for early detection of precrisis and cancer cells. The age-related
      m5C loss may result from accumulation of the m5C-->T+C transitions occurring with
      DNA methylation in every cell division.

PMID- 8557096
TI  - Within- and between-strain variability in longevity of inbred and outbred rats
      under the same environmental conditions.
AB  - The analysis of 26 longevity curves of different populations of inbred (Fischer
      344) and outbred (Sprague-Dawley) rats highlighted a remarkable between
      populations variability in survival parameters. This variability is independent
      of the breeding characteristics of the strain. The two strains differed in the
      slope of the survival curves, with Fischer 344 rats showing a higher survival
      over the second year of life as well as a lower interindividual variability. A
      model-free approach based on principal component analysis allowed us to quantify
      these differences and to high-light some limitations of the classical Gompertzian
      approach.

PMID- 8557097
TI  - Abnormal cell proliferation and p52/p35-CSK expression in the colons of aging
      rats.
AB  - In rodents and in humans, aging is associated with increased gastrointestinal
      epithelial cell proliferation and an expanded crypt proliferative compartment
      similar to that seen in the preneoplastic bowel. We have compared the
      distribution of a series of cytoskeletal antigens that are modified when colonic
      cancer cells differentiate in vitro in the colon of young (4-7 month) and aging
      (22-26 month) Fischer 344 rats. Two such proteins, p52 and p35, (that are
      increased in cultured senescent cells) differ in their position in the crypt axis
      and subcellular localization between young and aging rats. In young rats,
      immunoreactive p52 protein is present solely near the colonic crypt surface
      epithelium but in aging rats p52 expressing cells are found deeper in crypts. The
      intracellular localization of p35 also differs markedly in young and aging
      animals. The distribution of these proteins appears to be a reproducible
      biomarker of aging. Antigenic changes similar to those observed in aging colons
      also are seen in crypt cells of patients with ulcerative colitis and in the flat
      colonic mucosa of patients with adenomatous polyps and colon cancer. The
      combination of proliferative and differentiation changes suggest that the flat
      mucosa of the colon of aging rats has preneoplastic features.

PMID- 8557098
TI  - Effects of age on the pharmacodynamics of naproxen in the rat.
AB  - The pharmacodynamics of naproxen were evaluated in 5- and 24-month-old male
      Fischer 344 rats. Plasma naproxen concentrations and thromboxane B2 (TxB2)
      concentrations were measured as a function of time after intravenous
      administration of 25 mg/kg naproxen. Age-dependent alterations in naproxen
      pharmacokinetics were attributed to significant reductions in free plasma
      clearance (CLfree) and free steady-state volume of distribution (VSSfree),
      suggesting a decline in metabolic activity and naproxen binding to tissue
      components in aged rats, respectively. The time course of TxB2 production as a
      function of unbound naproxen concentrations was described by a sigmoid Emax
      model. Age had no significant effect on the pharmacodynamic parameter Emax, the
      maximum percent inhibition of TxB2 formation. Age also had no statistically
      significant effect on EC50, the drug concentration producing 50% of the maximum
      effect, however, average EC50 values were 35% higher in the aged rats. The
      duration of TxB2 inhibition was unaffected by age, possibly owing to similar
      relative decreases in receptor sensitivity (increased EC50) and increases in free
      naproxen concentrations (decreased free clearance and volume of distribution).
      Alternatively, the age-related changes in pharmacokinetic parameters were not of
      sufficient magnitude to produce a significant change in drug response, naproxen,
      pharmacokinetics, pharmacodynamics, age, rats, thromboxane B2, nonsteroidal anti
      inflammatory drugs.

PMID- 8557099
TI  - Geographic variations of life history strategies in Drosophila melanogaster. II.
      Analysis of laboratory-adapted populations.
AB  - Life history traits--hatchability, longevity, and egg production--of five wild
      caught populations of Drosophila melanogaster were measured after these
      populations had been reared in constant laboratory conditions during a 4-year
      period. The results were analyzed together with those that had been obtained with
      the same populations just after capture. They are probably the first convincing
      results that reveal the existence of genetic variability for some life history
      traits measured in the laboratory. Besides, no significant phenotypic
      correlations, either positive or negative, between early and late components of
      fitness were found. Finally, the five populations showed different patterns of
      genetic correlation between early and late fitness traits. One of the populations
      showed a negative correlation, another showed a positive correlation, while the
      remaining three populations showed no correlation at all. This was equally
      observed at the within- and between-population levels. That result suggests that
      both the antagonistic pleiotropy hypothesis proposed by Williams and the
      concordant pleiotropy hypothesis suggested by Lints are not of general validity.

PMID- 8557100
TI  - Aging of neurons in the mollusc Lymnaea stagnalis small parietal ganglion: a
      morpho-functional comparison in the same neuron.
AB  - The aim of this study was to compare the functional and structural changes in
      similarly identified neurons of the small parietal ganglion in 56 molluscs
      (Lymnaea stagnalis) of two age groups: adult (10-12 months) and old (20-22
      months). No age changes were found in the values of membrane potential,
      resistance of the neuronal membrane, amplitude, duration, or rate of increase of
      the anterior action potential front. With aging, the thresholds of direct
      stimulation were significantly increased, the rate of action potential
      repolarization decreased, and the amplitude of trace hyperpolarization decreased.
      The most marked age-dependent changes were observed in the frequency of neuronal
      spontaneous activity. A clear relationship was established between the frequency
      of action potentials of the neuron and its structure in adult and old individuals
      alike. In the molluscs of both age groups, the neurons with a high frequency of
      action potential displayed ultrastructural features of high activity in the
      organelles involved in protein biosynthesis. The cytoplasm of these neurons was
      filled with numerous ribosomes and had a well-developed rough endoplasmic
      reticulum. The structure of cells with low spontaneous activity in old molluscs
      differed considerably from that of the corresponding neurons of the adult
      individuals. The former had significantly marked morphological signs of reduction
      of the protein-synthesizing processes, as well as of destructive and dystrophic
      changes. A decrease in the lability of neurons may be an important mechanism of
      aging.

PMID- 8557101
TI  - Ascorbate is the natural substrate for plant peroxidases.
AB  - Ascorbate-dependent detoxification of hydrogen peroxide by guaiacol-type
      peroxidases is increased considerably in the presence of 3,4-dihydroxyphenolic
      compounds, suggesting that ascorbate is the natural substrate for many types of
      peroxidase in situ and not just the ascorbate-specific peroxidases. The ascorbate
      dependent destruction of hydrogen peroxide in the more acidic cellular
      compartments such as the vacuole may be an important function of such non
      specific peroxidases. The stress-induced production of phenolic compounds would
      render the guaiacol peroxidases in other less acidic-cellular sites effective as
      ascorbate-dependent H2O2-detoxifying enzymes.

PMID- 8557102
TI  - Stress signal, mediated by a Hog1-like MAP kinase, controls sexual development in
      fission yeast.
AB  - We identified the phh1+ gene that encodes a MAP kinase as the effector of Wis1
      MAP kinase kinase in fission yeast, which is highly homologous with HOG1 of S.
      cerevisiae. Heterothalic phh1 dsiruptant is phenotypically indistinguishable from
      wis1 deletion mutant, both displaying the same extent of partial sterility and
      enhanced sensitivity to a variety of stress. In phh1 disruptant, nitrogen
      starvation-induced expression of ste11+, a key controller of sexual
      differentiation, is markedly diminished. Ectopic expression of ste11+ effectively
      restores fertility, but not stress resistance, to the phh1 disruptant. These data
      show that stress signal, mediated by a MAP kinase, is required for efficient
      start of sexual differentiation.

PMID- 8557104
TI  - Identification of differentially expressed genes induced in pancreatic islet
      neogenesis.
AB  - Cellophane wrapping of the hamster pancreas induces islet neogenesis. We have
      used the mRNA differential display technique to select for genes expressed during
      islet neogenesis but not in control pancreata. Ten candidate clones have been
      identified. Upon sequencing, 6 clones showed a high degree of homology to known
      genes, 1 showed some, and 3 showed no homology to genes of known sequence. Thus,
      mRNA differential display is a useful technique to identify genes induced during
      islet neogenesis, and in combination with screening hamster pancreatic cDNA
      libraries for full length clones, will enhance the likelihood of capturing the
      participants in this process.

PMID- 8557103
TI  - Mucin-type glycoprotein from Drosophila melanogaster embryonic cells:
      characterization of carbohydrate component.
AB  - A secreted glycoprotein (GP) with apparent molecular mass of 90 kDa produced by
      cultured embryonic cells of Drosophila melanogaster was isolated and partially
      characterized. GP is enriched by Ser + Thr and Pro residues that constitute up to
      30% of the total number of amino acids. An abundant carbohydrate moiety (40% of
      molecular mass) is mainly represented by vertebrate mucin-type O-linked
      disaccharide units Gal(beta 1-3)-GalNAc, occupying about a half of the total
      number of Ser+Thr residues and rendering the GP molecule high resistance to
      protease action. A few of N-glycans are also present in GP. These characteristics
      allow to consider the Drosophila GP (termed 'mucin-D') as a first representative
      of invertebrate mucin-type glycoproteins.

PMID- 8557105
TI  - Synthesis and properties of cross-linked DNA duplexes.
AB  - A method has been devised to synthesize DNA duplexes with covalently connected
      strands. The structure of cross-linked duplexes was confirmed by a reaction with
      the restriction endonuclease AluI. The thermal stability of the resulting
      compounds was investigated.

PMID- 8557106
TI  - Processing of pro-islet amyloid polypeptide (proIAPP) by the prohormone
      convertase PC2.
AB  - Islet amyloid polypeptide (IAPP), 'amylin', is the component peptide of islet
      amyloid formed in Type 2 diabetes. IAPP is expressed in islet beta-cells and is
      derived from a larger precursor, proIAPP, by proteolysis. An in vitro
      translation/translocation system was used to separately examine processing of
      human proIAPP by the beta-cell endopeptidases PC2, PC3 or furin. ProIAPP was
      converted to mature IAPP by PC2 but there was little conversion by furin or PC3.
      These data are consistent with processing of proIAPP in beta-cell secretory
      granules. Abnormal cellular proteolysis associated with type 2 diabetes could
      contribute to IAPP amyloidosis.

PMID- 8557107
TI  - Evolutionary relationship of hepatitis C, pesti-, flavi-, plantviruses, and newly
      discovered GB hepatitis agents.
AB  - Two flavivirus-like viruses, GB virus-A (GBV-A) and GB virus-B (GBV-B), were
      recently identified in the GB hepatitis agent, and are distinct from the
      hepatitis A to E viruses. The putative helicase domain of GBV-A and GBV-B was
      found to have amino acid sequence homology with hepatitis C virus (HCV), and
      distantly, is also related to pestiviruses, flaviviruses, and plant viruses. A
      phylogenetic tree construction showed that GBVs and HCV are closely related, and
      they are clustered with pestiviruses, flaviviruses and plant viruses in that
      order.

PMID- 8557108
TI  - Dansyl cadaverine regulates ligand induced endocytosis of interleukin-8 receptor
      in human polymorphonuclear neutrophils.
AB  - Interleukin-8 (IL-8), a neutrophil chemotactic agent, acts as a key mediator in a
      large number of acute and chronic inflammatory diseases. At 37 degrees C, the
      receptor for IL-8 is rapidly internalized with its ligand. But no specific
      inhibitor of this ligand induced internalization of the receptor has been
      reported so far. We have found that monodansyl cadaverine (MDC) inhibited about
      70% of IL-8 induced endocytosis and caused 70% and 66% inhibition of IL-8
      mediated chemotaxis and respiratory burst response, respectively, in neutrophils.
      The uninternalized receptor was detected by anti IL-8R antibody in MDC treated
      cells. The endocytosis of IL-8R was strongly inhibited under Ca2+ depleted
      conditions which was restored on addition of 1 mM CaCl2 indicating the critical
      involvement of a Ca2+ ion in the process. Absence of receptor internalisation
      makes the MDC treated neutrophils suitable for studying the interaction of IL-8R
      with potential therapeutic agents e.g. for in vitro screening of anti
      inflammatory agents.

PMID- 8557109
TI  - Purification and characterization of the acetate forming enzyme, acetyl-CoA
      synthetase (ADP-forming) from the amitochondriate protist, Giardia lamblia.
AB  - Giardia lamblia, an amitochondriate eukaryote, contains acetyl-CoA synthetase
      (ADP-forming), an enzyme known only from one other eukaryote (Entamoeba
      histolytica) and a few anaerobic prokaryotes. The enzyme has been purified about
      350-fold. The activity in the direction of acetate formation was dependent on ADP
      and inorganic phosphate. The reverse reaction could not be detected. Succinyl
      CoA, propionyl-CoA and dADP were utilized with lower efficiency. The enzyme did
      not utilize AMP plus PPi thus differs from the broadly distributed acetyl-CoA
      synthetase (AMP-forming). The enzyme is responsible for acetate production
      accompanied by ATP generation, thus plays an important role in G. lamblia
      metabolism.

PMID- 8557110
TI  - Cloning and expression of a bovine adenylyl cyclase type VII specific to the
      retinal pigment epithelium.
AB  - A cDNA of a type 7 adenylyl cyclase isoform was cloned from a bovine retinal
      pigment epithelium cDNA library using oligonucleotides developed to conserved
      regions common to mammalian adenylyl cyclases. A 6.7 kb mRNA of very high
      abundance was uniquely present on Northern blots containing mRNA or total RNA
      from the pigment epithelium. This transcript was undetectable in all other
      tissues examined. The cDNA encoded a protein of 1,097 amino acids and exhibited
      the known doublet of 6 transmembrane-spanning regions in a hydrophobicity plot.
      The novel member of the type 7 adenylyl cyclase isoform was expressed in COS-1
      cells. It was stimulated 10- and 20-fold by 10 microM GTP gamma S and 100 microM
      forskolin, respectively. The high expression rate exclusively in the retinal
      pigment epithelium suggests that this adenylyl cyclase isoform is involved in
      processes specific to this functionally exceedingly important subretinal cell
      layer.

PMID- 8557111
TI  - The modulation of the rate of inactivation of the mKv1.1 K+ channel by the beta
      subunit, Kv beta 1 and lack of effect of a Kv beta 1 N-terminal peptide.
AB  - The coexpression of the rat Kv beta 1 subunit with the mouse Kv1.1 (mKv1.1) K+
      channel in Chinese hamster ovary cells caused an increase in the rate of
      inactivation of whole-cell current. Current decayed in a bi-exponential fashion
      with a fast voltage-dependent and a slower voltage-independent component. The
      inactivating current component accounted for around 40% of the total outward
      current. In contrast to previous studies using K+ channel alpha subunits,
      peptides based on the N-terminal of the Kv beta 1 subunit were unable to mimic
      the action of the entire subunit. The findings indicate differences between the
      inactivation induced by the Kv beta 1 subunit and the N-type inactivation
      mechanism associated with certain rapidly-inactivating cloned K+ channel alpha
      subunits.

PMID- 8557112
TI  - The high-affinity binding of Clostridium botulinum type B neurotoxin to
      synaptotagmin II associated with gangliosides GT1b/GD1a.
AB  - 125I-labeled botulinum type B neurotoxin was shown to bind specifically to
      recombinant rat synaptotagmins I and II. Binding required reconstitution of the
      recombinant proteins with gangliosides GT1b/GD1a. Scatchard plot analyses
      revealed a single class of binding site with dissociation constants of 0.23 and
      2.3 nM for synaptotagmin II and synaptotagmin I, respectively, values very
      similar to those of the high- (0.4 nM) and low-affinity (4.1 nM) binding sites in
      synaptosomes. The high-affinity binding of neurotoxin to synaptosomes was
      specifically inhibited by a monoclonal antibody recognizing with the amino
      terminal region of synaptotagmin II. These results suggest that this region of
      synaptotagmin II participates in the formation of the high-affinity toxin binding
      site by associating with specific gangliosides.

PMID- 8557113
TI  - Cap Z, a calcium insensitive capping protein in resting and activated platelets.
AB  - Capping of the barbed-ends of actin filaments is an important mechanism for
      control of the cytoskeleton. In platelets, a valuable model system, it has been
      thought that gelsolin was the major capping protein. We now report that platelets
      contain approximately 2 microM Cap Z, a calcium insensitive heterodimeric capping
      protein; two major and additional minor isoforms of both alpha and beta subunits
      are present. In lysates from resting platelets 75-80% of the Cap Z sediments with
      the high speed pellet, but if the platelets are activated with thrombin for 10 s,
      about 15% of the Cap Z leaves the pellet fraction and is found in the high speed
      supernatant where it is not bound to actin. This translocation of Cap Z to the
      supernatant is also observed when resting platelets are lysed into buffer
      containing 50-100 microM GTP gamma S and 10 mM EGTA. Our results suggest that
      release of Cap Z from some actin filaments could generate free filament barbed
      ends. An increase in free barbed-ends has been reported in platelet lysates
      prepared shortly after thrombin activation.

PMID- 8557114
TI  - A circularly permuted alpha-amylase-type alpha/beta-barrel structure in glucan
      synthesizing glucosyltransferases.
AB  - A motif of amino acid residues, located at the active site and specific beta
      strands in alpha-amylases, is recognized in alpha-1,3- and alpha-1,6-glucan
      synthesizing glucosyltransferases, leading to the conclusion that these enzymes
      contain an alpha/beta-barrel closely related to the (beta/alpha)8-fold of the
      alpha-amylase superfamily. The secondary structure elements of the transferase
      barrel, however, are circularly permuted to start with an alpha-helix equivalent
      to helix 3 in the alpha-amylases. Thus, the transferase counterpart of the long
      third beta-->alpha connection--constituting a domain in the alpha-amylases--is
      divided to precede and succeed the barrel. This architectural arrangement may be
      coupled to sucrose scission and glucosyl transfer. The involvement in the
      mechanism in glucosyltransferases of active site residues recurring in amylolytic
      enzymes is discussed.

PMID- 8557115
TI  - Augmented expression of obese (ob) gene during the process of obesity in
      genetically obese-hyperglycemic Wistar fatty (fa/fa) rats.
AB  - Expression of the obese (ob) gene is up-regulated in the adipose tissue in
      several obese rodent models. To study the regulation of the ob gene expression
      during the development of obesity, we examined the ob gene expression in
      genetically obese-hyperglycemic Wistar fatty (fa/fa) rats at several stages of
      obesity. The ob mRNA levels in the adipose tissue from Wistar fatty rats was
      unequivocally augmented and continued to rise in the process of obesity.
      Furthermore, the ob gene expression in this obese model was much more rapidly
      enhanced in the mesenteric fat than in the subcutaneous fat. Moreover, the ob
      gene expression was more greatly augmented in the mesenteric fat than the
      lipoprotein lipase gene expression. These results suggest the presence of obesity
      linked and region-specific regulation of the ob gene expression.

PMID- 8557116
TI  - Presence of long and short dystrophin and/or utrophin products in Torpedo
      marmorata peripheral nerves.
AB  - Peripheral nerves from rabbit and Torpedo marmorata were comparatively analyzed
      for the presence of short dystrophin products. Western blot analyses of Torpedo
      marmorata peripheral nerve extracts revealed the existence of three proteins
      belonging to the dystrophin family: a M(r) 400 kDa protein band detected with
      dystrophin/utrophin, dystrophin-specific and Torpedo utrophin-specific
      antibodies, a molecule identified as Dp116 and, for the first time at the protein
      level, a new protein probably corresponding to Up116. All of these products were
      carefully identified according to the specificities of the monoclonal antibodies
      used. In immunofluorescence studies, clear staining of the thin rim surrounding
      each Schwann cell-axon unit was observed in both Torpedo marmorata and rabbit
      peripheral nerves, showing colocalization of all of these molecules. Their
      potential functions were discussed in comparison to similar products found in
      rabbit peripheral nerves.

PMID- 8557117
TI  - Evidence for an association of ndh B, ndh J gene products and ferredoxin-NADP
      reductase as components of a chloroplastic NAD(P)H dehydrogenase complex.
AB  - Using non-denaturing gel electrophoresis and staining with nitro-blue
      tetrazolium, we reveal the presence of two NAD(P)H oxidoreductase activity bands
      within thylakoids membranes of Solanum tuberosum L. Second dimension SDS-PAGE and
      Western analysis show that one of the activity bands contains several
      polypeptides, two of them being recognized by antibodies directed against
      peptides corresponding to conserved domains of chloroplastic genes products NDH B
      and NDH J (at 32 and 18 kDa, respectively). Both activity bands also contain a
      polypeptide (around 36 kDa) recognized by an antibody directed against ferredoxin
      NADP(+)-reductase (FNR). We conclude from these results that both chloroplastic
      ndh B and ndh J gene products are components of a thylakoid NAD(P)H dehydrogenase
      complex. The association with FNR is suggested to allow the complex to use NADPH
      instead of NADH as a preferential substrate.

PMID- 8557118
TI  - PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine
      163.
AB  - The 80kDa Myristolated Alanine-Rich C-Kinase Substrate (MARCKS) is a major in
      vivo substrate of protein kinase C (PKC). Here we report that MARCKS is a major
      substrate for the lipid-activated PKC-related kinase (PRK1) in cell extracts.
      Furthermore, PRK1 is shown to phosphorylate MARCKS on the same sites as PKC in
      vitro. Thus, control of MARCKS phosphorylation on these previously identified
      'PKC' sites may be regulated under certain circumstances by PRK as well as PKC
      mediated signalling pathways. The implications for MARCKS as a marker of PKC
      activation and as a point of signal convergence are discussed.

PMID- 8557119
TI  - Effects of N-terminal deletions on 1-aminocyclopropane-1-carboxylate synthase
      activity.
AB  - A series of nested N-terminal deletions were made on the full-length (wt) and C
      terminal deleted (Cdel) 1-aminocyclopropane-1-carboxylate synthase cDNAs. These
      wt and mutant ACC synthases were over-expressed in a heterologous E. coli
      expression system. It was found that removal of an amino acid region (residues 2
      12) from the non-conserved N-termini of wt and Cdel ACC synthases led to a slight
      increase in both in vivo ACC production and in vitro ACC synthase activity.
      Further deletion of 11 amino acids through Glu-23 from the N-termini of both wt
      and Cdel ACC synthases resulted in a substantial reduction in both in vivo ACC
      production and in vitro enzyme activity. Deletion of an amino acid region,
      residues 3 through 27, from the N-terminus of ACC synthase abolished enzyme
      activity completely. Kinetic analysis of a highly purified double-deletion mutant
      (NCdel-1) of ACC synthase demonstrated that the Km of this mutant is 42 microM,
      which is much smaller than that of the corresponding Cdel (280 microM) and closer
      to that of wt (22 microM) reported previously, suggesting a clear effect of the
      non-conserved N-terminal region on its ACC synthase function.

PMID- 8557120
TI  - Pentacoordination of the heme iron of Arthromyces ramosus peroxidase shown by a
      1.8 A resolution crystallographic study at pH 4.5.
AB  - In the presence of ammonium sulfate the absorption spectra of a peroxidase from
      the fungus Arthromyces ramosus (ARP) showed that the low-spin component increased
      as the pH increased from 6.0 to 9.0, whereas in its absence ARP remained in the
      high-spin state in the pH range investigated. The crystal structure of ARP at pH
      4.5 in the presence of ammonium sulfate at 1.8 A resolution showed that the
      electron density at the 6th position of the heme iron seen at pH 7.5 had
      disappeared and that the iron atom deviated markedly from the heme plane. These
      observations strongly suggest that under physiological conditions the heme of ARP
      is in the pentacoordinated high-spin state and that at a high pH the heme iron is
      able to bind ammonia, forming the low-spin state. The location of the water
      molecule at the distal side of the heme in peroxidases is also discussed.

PMID- 8557122
TI  - Achieving multiple-order embryo transfer identifies women over 40 years of age
      with improved in vitro fertilization outcome.
AB  - OBJECTIVE: To define factors in patients > or = 40 years that may improve outcome
      and provide prognosis for success in IVF-ET. DESIGN: Retrospective. SETTING:
      University infertility center. PATIENTS: Patients (n = 501) undergoing IVF-ET
      from 1987 to 1994. INTERVENTIONS: IVF-ET (n = 713 cycles) with GnRH-analogue
      suppression and hMG stimulation. MAIN OUTCOME MEASURES: We evaluated data
      including age, diagnosis, prestimulation (day 3) FSH and E2, hMG ampules used,
      days of monitoring, follicle number and size, maximum E2, ova retrieved,
      cancellation rate, clinical pregnancy, nidation, and miscarriage rates. RESULTS:
      Overall, patients > or = 40 years had significantly decreased pregnancy rates
      (PRs), response to stimulation, and increased miscarriage rates. However, if
      these patients had four or more embryos transferred, their response and PRs
      (34.4% per ET) were not significantly different from younger women (47.7% per
      ET). The majority (77.8%) of pregnancies in women > or = 40 years occurred when
      four or more embryos were transferred. CONCLUSION: A subset (49%) of women > or =
      40 years undergoing IVF-ET will respond to ovarian stimulation well enough to
      result in four or more embryos available for transfer with a resultant PR similar
      to that observed in younger patients. We recommend consideration of an attempt at
      IVF-ET before recommending oocyte donation.

PMID- 8557121
TI  - Polycystic ovary syndrome: pathophysiology and outcome with in vitro
      fertilization.
AB  - OBJECTIVE: To assess the efficacy of IVP-ET in infertile women with the
      polycystic ovary syndrome (PCOS) and to provide a comprehensive review of
      contemporary therapeutic options and their complications as reflected in the
      current literature. DESIGN: Pertinent studies in medical literature identified
      through computerized bibliographic search and via manual review of relevant
      scientific publications. RESULTS: In vitro fertilization and ET is an effective
      therapy for PCOS patients who are refractory to ovulation induction in vivo or
      who have coexisting infertility factors. The use of GnRH agonist (GnRH-a) is
      associated with significant reductions in the incidence of pregnancy loss and may
      improve fertilization and cleavage rates. In the PCOS patient, the use of
      purified FSH preparations does not appear to improve pregnancy rates nor other
      clinical parameters when compared with hMG. Severe ovarian hyperstimulation
      syndrome (OHSS) is an important consideration when PCOS patients undergo
      superovulation protocols. Strategies for OHSS prevention include the use of
      intravenous albumin immediately after oocyte retrieval, triggering of ovulation
      with a GnRH-a, or withholding menotropin therapy for several days before hCG
      administration. Cryopreservation of all embryos for future transfer in an
      artificial cycle has also proven to be an effective alternative in PCOS patients
      at high risk for severe OHSS. CONCLUSIONS: Pregnancy rates for PCOS patients
      undergoing IVF-ET are comparable with those for women with tubal factor
      infertility. Therefore, IVF-ET should be offered to patients with PCOS who are
      refractory to conventional infertility modalities.

PMID- 8557123
TI  - A prospective randomized study comparing needles of different diameters for
      transvaginal ultrasound-directed follicle aspiration.
AB  - OBJECTIVE: To determine whether the use of smaller diameter needles at oocyte
      collection reduces pain without jeopardizing the treatment outcome. DESIGN:
      Prospective randomized study. SETTING: The Assisted Conception Unit, Kings
      College Hospital, United Kingdom. PATIENTS: One hundred twelve patients
      undergoing an IVF-ET treatment cycle. INTERVENTIONS: Study patients were aged <
      or = 38 years and had at least six follicles > 14 mm on the day of oocyte
      collection. Patients were randomized to follicle aspiration with a 15- (n = 34),
      17- (n = 41), or 18- (n = 37) gauge (g) single channel needle. Intravenous
      pethidine and diazepam were used for analgesia and sedation. Pain was quantified
      by means of questionnaires completed by the patient and by her partner
      postoperatively. RESULTS: A greater proportion of patients reported severe to
      unbearable pain with the 15-gauge compared with the 17-gauge (44% versus 22%) or
      18-gauge (44% versus 16%) needles. Partners' perception of severe pain
      experienced by patients showed the same trend when the 15-gauge was compared with
      the 17- (62% versus 29%) and 18-gauge (62% versus 22%) needles. There was no
      significant difference between the needles regarding the oocyte collection rate,
      fertilization rate, proportion of oocytes with fractured zonae, cleavage rate,
      implantation rate, and pregnancy rate per cycle. CONCLUSIONS: Reducing the size
      of the needle used for oocyte collection from 15 to 17 or 18 gauge reduces pain
      without affecting the number of oocytes collected, their quality, or the clinical
      pregnancy rate.

PMID- 8557124
TI  - Legal troublespots in assisted reproduction.

PMID- 8557125
TI  - Relationship of timing of agonist administration in the cycle phase to the
      ovarian response to gonadotropins in the long down-regulation protocols for
      assisted reproductive technologies.
AB  - OBJECTIVE: To assess whether the ovarian response to exogenous gonadotropins and
      cycle performance is affected by different timing of an agonist administration in
      long down-regulation protocols. DESIGN: An agonist was administered irrespective
      of cycle phase, with exogenous gonadotropin beginning 15 days later. PATIENTS:
      Five hundred fifty-seven normovulatory infertile patients, aged < or = 38 years,
      were classified into seven study groups, depending on the phase of the cycle in
      which agonist was started. MAIN OUTCOME MEASURES: Endocrine profile, amount of
      exogenous stimulation, occurrence of ovarian cysts, mean number of oocytes
      recovered and embryos transferred, pregnancy rate, implantation rate, and live
      birth rate of the seven groups. RESULTS: The ovarian response of the groups did
      not show any statistically significant differences in relation to the initiation
      of the agonist. The only effect was a different incidence of ovarian cyst
      formation, but this phenomenon did not affect cycle performance. The pregnancy,
      implantation, and live-birth rates showed differences that did not reach
      statistical significance. CONCLUSION: Agonists initiation can be programmed in
      advance irrespective of the phase of the cycle. This approach can be of help for
      the logistics of assisted reproduction programs.

PMID- 8557126
TI  - The long-acting gonadotropin-releasing hormone analogues impaired the
      implantation rate.
AB  - OBJECTIVES: To determine the efficacy and innocuousness of long-acting versus
      short-acting GnRH analogues (GnRH-a) in long protocol for in IVF-ET. DESIGN:
      Prospective randomized study. SETTING: The IVF unit at an academic hospital.
      PATIENTS: One hundred couples admitted for their first IVF-ET attempt. MAIN
      OUTCOME MEASURES: Serum concentrations of LH, E2, and P during the all cycles and
      duration of pituitary desensitization were assessed, as well as fertilization
      rate, embryo quality, and implantation and pregnancy rates. RESULTS:
      Significantly more days (10.8 +/- 1.8 versus 9.2 +/- 1.7 days) of stimulation and
      more ampules of hMG (47 +/- 22 versus 33 +/- 16) were necessary to obtain similar
      numbers of embryos of quality with the long-acting GnRH-a. Implantation and
      delivery rates were significantly lower with the long-acting GnRH-a (32.8% versus
      21.1%; 48.9% versus 29.1%, respectively). CONCLUSIONS: As the long-acting GnRH-a
      might interfere with the luteal phase and embryo development, short-acting GnRH-a
      should be preferred for ovarian hyperstimulation in IVF-ET.

PMID- 8557127
TI  - The influence of sperm morphology and the number of motile sperm inseminated on
      the outcome of intrauterine insemination combined with mild ovarian stimulation.
AB  - OBJECTIVE: To determine the influence of sperm morphology and the number of
      motile sperm inseminated on the outcome of IUI in hMG-stimulated cycles and to
      establish lower limits for these variables below which the expectation of
      pregnancy is limited. DESIGN: Retrospective study of data from 1990 to 1992.
      SETTING: Tertiary referral Reproductive Medicine Unit. PATIENTS: Couples with
      bilaterally patent fallopian tubes, and > or = 200,000 motile sperm recovered in
      a trial preparation before treatment. No other semen criteria were used to
      exclude couples. Women were stimulated with hMG irrespective of whether they were
      ovulatory or anovulatory. The study comprised 163 couples who underwent 330
      cycles. MAIN OUTCOME MEASURES: Pregnancy rate (PR) per cycle was related to the
      percentage normal sperm morphology in the fresh semen sample and the number of
      motile sperm inseminated after sperm preparation by swim-up or Percoll gradients.
      RESULTS: The overall PR was 16.1% per cycle. The PR was highest in the first
      cycle of treatment (21.4%) and declined in the second and third cycles. The
      miscarriage rate was 10.4% and the incidence of multiple pregnancies was 13.9%.
      Two groups of patients were defined on the basis of sperm morphology: a "poor
      outcome" group ( < or = 10% normal) and a "good outcome" group ( > 10% normal).
      The PRs in these two groups were 4.3% and 18.2%, respectively, and the cumulative
      PRs after three cycles were 8.3% and 40.1%, respectively. The number of motile
      sperm inseminated did not significantly affect the PR. CONCLUSIONS: The degree of
      teratozoospermia affected the PR in hMG-stimulated IUI cycles and a normal
      morphology value of 10% in the fresh semen distinguished couples with good and
      poor outcomes. In contrast, the number of motile sperm inseminated did not
      significantly influence IUI outcome.

PMID- 8557128
TI  - Human menopausal gonadotropin and the risk of epithelial ovarian cancer.
AB  - OBJECTIVE: To determine whether women with epithelial ovarian cancer are more
      likely to have been exposed to fertility drugs, and in particular hMG, than
      healthy population controls. DESIGN: A nationwide case-control study. PATIENTS:
      Two hundred living women 36 to 64 years of age, with a histologically confirmed
      diagnosis of primary invasive or borderline epithelial ovarian cancer that was
      first diagnosed and reported to the Israel Cancer Registry between January 1,
      1990 and September 1, 1993 were enrolled. There were 164 (82%) invasive and 36
      (18%) borderline epithelial ovarian tumors among the 200 cases. The controls were
      408 women from the same dialing areas selected by random digit dialing. Cases and
      controls were interviewed using a standard questionnaire. A multivariate logistic
      model was used to assess the association of fertility drug use and ovarian
      cancer, controlling for variables found to be statistically associated with this
      outcome on univariate analysis. RESULTS: Twenty-four women with epithelial
      ovarian cancer (12%) and 29 healthy controls (7.1%) reported that they had used
      any fertility drug (adjusted odds ratio [OR] 1.31; 95% confidence interval [CI]
      0.63 to 2.74). Among cases and controls, respectively, 22 and 24 reported that
      they had used hMG alone or in combination with clomiphene citrate (adjusted OR
      1.42, 95% CI 0.65 to 3.12), and 11 and 6 reported that they had used hMG alone
      (adjusted OR 3.19, (95% CI 0.86 to 11.82). The risk was increased particularly in
      the subgroup of women with borderline ovarian tumors who had used hMG (adjusted
      OR 9.38, 95% CI 1.66 to 52.08). CONCLUSIONS: We conclude that the use of
      ovulation induction agents, in particular hMG, may increase the risk of
      epithelial ovarian tumors.

PMID- 8557129
TI  - The efficacy of immunotherapy in patients who underwent superovulation with
      intrauterine insemination.
AB  - OBJECTIVE: To determine if the immunotherapy with corticosteroids would improve
      pregnancy rate in infertile patients with ovulatory factor and patients with
      unexplained infertility who undergo superovulation with IUI. DESIGN: Prospective,
      controlled study. SETTING: Division of Reproductive Endocrinology and
      Infertility, Department of Obstetrics and Gynecology, University of Ulsan, Seoul,
      Korea. PATIENTS: Nine-one infertile patients with ovulatory factors and 78
      patients with unexplained infertility who underwent superovulation with IUI.
      RESULTS: The prevalence of autoantibodies (antinuclear antibody, lupus
      anticoagulant, anticardiolipin antibody, antidouble-stranded DNA antibody) was
      elevated significantly in patients with unexplained infertility compared with
      patients with ovulatory infertility (20.5% versus 3.3%). Forty-five patients with
      ovulatory factor underwent 72 cycles of superovulation with IUI, receiving
      corticosteroids. Thirty-eight patients with unexplained infertility underwent 75
      cycles of superovulation with IUI, receiving corticosteroids. Forty-six patients
      with ovulatory factor who underwent 66 cycles of superovulation with IUI and 40
      patients with unexplained infertility who underwent 75 cycles of superovulation
      with IUI served as controls, not receiving corticosteroids. In patients with
      ovulatory factor, there were no significant differences between the
      corticosteroid treatment group and control group in clinical pregnancy rate
      (38.9% versus 33.3%) or in spontaneous abortion rate (14.3% versus 13.6%). In
      patients with unexplained infertility, there was a significantly higher clinical
      pregnancy rate per cycle in the corticosteroid treatment group, with 45.3%
      (34/75) compared with 29.3% (22/75) in the control group but no difference
      between the corticosteroid treatment and control groups in spontaneous abortion
      rate (17.6% versus 13.6%). There were no side effects due to the use of
      corticosteroids.

PMID- 8557130
TI  - Use of a specific zona pellucida (ZP) protein 3 antiserum as a clinical marker
      for human ZP integrity and function.
AB  - OBJECTIVE: To evaluate binding characteristics of a specific zona pellucida (ZP)
      protein 3 (ZP3) antiserum to human oocytes in order to determine its usefulness
      as a clinical marker for human ZP integrity and function and its correlation with
      IVF outcome. DESIGN: Prospectively designed, blinded, internally controlled
      study. SETTING: Tertiary care academic center. PATIENTS: Patients undergoing IVF
      therapy who had either total failed fertilization or partial fertilization were
      studied. INTERVENTIONS: Metaphase II oocytes showing absence of pronuclear
      formation were salt stored 48 hours after insemination and bisected into matching
      hemizonae using micromanipulation. One hemizona was incubated with AS ZP3-6 (an
      antiserum generated against a synthetic ZP3 peptide derived from an amino acid
      sequence that is highly conserved in the structure of ZP3), whereas the matching
      hemizona was incubated with AS ZP3-7, an antiserum detecting exclusively mouse
      ZP3 (internal, negative control). Antibody binding was visualized using the
      peroxidase-antiperoxidase method and diaminobenzidine as color reagent. RESULTS:
      A total of 104 unfertilized oocytes were evaluated. Analysis of variance showed a
      significant interaction between gamete factor groups (sperm and oocyte) and
      antiserum factor. Patients with oocyte factor had significantly lower mean
      staining scores for the AS ZP3-6-treated hemizonae than patients with sperm
      factor. CONCLUSIONS: These results demonstrate that anomalies of human ZP3 can be
      identified with AS ZP3-6 and that these ZP abnormalities correlate with
      fertilization failure during IVF treatment. Thus, this newly developed biomarker
      may be of clinical significance in the identification of oocyte defects that are
      associated with fertilization disorders and may help in the decision-making
      process in the IVF-assisted fertilization setting.

PMID- 8557132
TI  - Manual versus computer-automated semen analyses. Part I. Comparison of counting
      chambers.
AB  - OBJECTIVE: To determine the accuracy and precision of counting chambers analyzed
      manually and with a computer-automated semen analyzer (CASA; Hamilton-Thorne
      Research, Beverly, MA). DESIGN: Prospective study using comparative measurements
      of sperm concentration, motility and concentration of latex beads with three
      types of counting chambers: hemacytometers, 12 and 20 MicroCell (Conception
      Technologies, Inc., La Jolla, CA) Chambers, and Makler (Sefi-Medical Instruments,
      Haifa, Israel) Chambers. SETTING: A hospital-based Andrology laboratory.
      PATIENTS: Male partners of couples undergoing infertility evaluation. MAIN
      OUTCOME MEASURES: Experiment I: measurements of sperm concentration were
      evaluated within hemacytometers; Experiment II: measurements of sperm
      concentration in the 35 to 50 x 10(6)/mL range and sperm motility were determined
      using a known concentration of beads. RESULTS: Experiment I: differences were
      demonstrated within two of eight hemacytometers (side 1 versus side 2): however,
      no significant effect of hemacytometer on variation in sperm concentration
      measurements was observed. Experiment II: CASA-analyzed 20 MicroCell Chambers
      demonstrated the best precision for sperm concentration (intraclass correlation
      coefficient = 0.93) and motility (intraclass correlation coefficient = 0.88).
      Experiment III: 20 MicroCell Chambers most accurately determined known bead
      concentration (35 +/- 5 x 10(6)/mL) whether analyzed on CASA (34.9 x 10(6)/mL) or
      manually (35.2 x 10(6)/mL). CONCLUSIONS: 20 MicroCell Chambers proved to be
      accurate and precise for determining concentration and motility of semen
      specimens whether analyzed manually or with CASA.

PMID- 8557131
TI  - Does serologic evidence of remote Chlamydia trachomatis infection and its heat
      shock protein (CHSP 60) affect in vitro fertilization-embryo transfer outcome?
AB  - OBJECTIVE: To examine IVF-ET outcome in patients with and without serologic
      evidence of Chlamydia trachomatis infection and chlamydia heat shock protein 60
      (CHSP 60) antibodies. DESIGN: Retrospective case control. SETTING: University
      affiliated IVF-ET program. MAIN OUTCOME MEASURES: A total of 195 IVF-ET patients
      with tubal factor infertility underwent oocyte pick-up, 166 of these women had ET
      resulting in a total of 37 pregnancies. Serum antibody testing for evidence of
      remote C. trachomatis and CHSP 60, as well as pregnancy outcome, were determined
      for all patients. RESULTS: There were no differences in pregnancy rates or
      outcomes between C. trachomatis seropositive versus seronegative groups: 27/118
      (23%) C. trachomatis seropositive versus 10/77 (13%) C. trachomatis seronegative
      patients achieved pregnancy per oocyte pick-up. Pregnancy rates per ET were
      27/105 (26%) in C. trachomatis seropositive versus 10/61 (16%) C. trachomatis
      seronegative patients. In the C. trachomatis positive subgroup, significantly
      higher pregnancy rates were found in the CHSP 60 antibody positive patients:
      24/67 (36%) CHSP 60 positive versus 3/51 (6.0%) CHSP 60 negative patients were
      pregnant after oocyte pick-up (OR = 8.9, 95% CI = 2.3 to 27.5). Pregnancy rates
      per ET were 24/57 (42%) in CHSP 60 positive versus 3/48 (7%) CHSP 60 negative
      patients (OR = 10.9, 95% CI = 2.8 to 33.6). There were no significant differences
      in any group when examining the following pregnancy outcomes: spontaneous
      abortion, ectopic pregnancy, preterm and multiple pregnancy rates. CONCLUSIONS:
      [1] There are no differences in pregnancy rates or outcomes in patients with and
      without serologic evidence of previous C. trachomatis infections. [2] In women
      seropositive for C. trachomatis, significantly higher pregnancy rates are found
      in women who are CHSP 60 antibody positive versus negative. [3] Pregnancy
      outcomes do not appear to be different between these groups.

PMID- 8557133
TI  - Manual versus computer-automated semen analyses. Part II. Determination of the
      working range of a computer-automated semen analyzer.
AB  - OBJECTIVE: To determine the accuracy and precision of a computer-automated semen
      analyzer (CASA; Hamilton-Thorne Research, Beverly, MA) over a wide range of sperm
      concentrations. DESIGN: Prospective study using comparative measurements of sperm
      concentration and motility were performed using manual and CASA methods of
      analyses. SETTING: A hospital-based Andrology laboratory. PATIENTS: Male partners
      of couples undergoing infertility evaluation. MAIN OUTCOME MEASURES: Measurements
      of sperm concentration in the range of 1 to 200 x 10(6)/mL were performed using
      hemacytometers and CASA-analyzed 20 MicroCell counting chambers (Conception
      Technologies, Inc., La Jolla, CA). Accuracy was assessed by comparison to the
      hemacytometer ("gold standard"). The MicroCell counting chambers also were used
      for manual and CASA sperm motility determinations. RESULTS: The CASA-analyzed 20
      Microcell Chamber most precisely determined sperm concentration in the 1 to 200 x
      10(6)/mL range (intraclass correlation coefficient = 0.94). The hemacytometer was
      least precise (intraclass correlation coefficient = 0.91). There was a high
      degree of correlation between the manually and CASA-analyzed MicroCell Chambers
      in the sperm concentration range of 20 to 149 x 10(6)/mL. Above and below this
      range, correlation was lower. Motility was determined most precisely using the
      CASA-analyzed 20 MicroCell Chamber. CONCLUSIONS: The Hamilton-Thorne CASA used
      with the 20 MicroCell Chamber is a precise and accurate method for determining
      sperm concentration and motility of semen specimens with concentrations in the 20
      to 149 x 10(6)/mL range. This same combination of CASA and MicroCell Chamber
      provides precise sperm motility results.

PMID- 8557134
TI  - Nuclear maturity of human spermatozoa selected by swim-up or by Percoll gradient
      centrifugation procedures.
AB  - OBJECTIVE: To investigate the relationship between sperm preparation techniques
      and nuclear maturity, as evidenced by the electrophoretic profiles of sperm
      nuclear proteins. DESIGN: Analysis of sperm nuclear quality in sperm populations
      used for IVF. SETTING: Center for infertility and assisted reproductive
      technology and university departments. PATIENTS: Twenty-seven men undergoing an
      infertility work-up. MAIN OUTCOME MEASURES: Comparative electrophoretic
      investigation of nucleoproteins extracted from spermatozoa selected by swim-up or
      Percoll techniques. RESULTS: Nuclear maturity level is improved after the two
      methods of selection but is more improved after Percoll. In the two groups,
      selected spermatozoa contain less histones. Moreover, Percoll gradients appeared
      to enrich for spermatozoa with less intermediate proteins and more mature
      nucleoproteins of P2 family than swim-up spermatozoa. CONCLUSION: Percoll may
      offer advantages in terms of the quality of the selected spermatozoa that may
      influence the outcome of assisted conception techniques.

PMID- 8557135
TI  - Impaired growth hormone secretion and increased growth hormone-binding protein
      levels in subfertile males.
AB  - OBJECTIVE: To evaluate GH secretion in subfertile males. DESIGN: Comparing GH
      secretion to a GH stimulation test in two different patient groups and in a
      control group. PATIENTS: Nine oligozoospermic patients, nine asthenozoospermic
      patients, and nine age- and body mass index-matched fertile males with normal
      spermograms. INTERVENTION: All subjects underwent an IV arginine GH stimulation
      test. MAIN OUTCOME MEASURES: Serum levels of FSH, LH, PRL, E2, T, insulin-like
      growth factor I (IGF-I), and GH-binding protein were measured. RESULTS: Basal
      levels of GH were similar in all three groups and serum GH increased in all
      groups after arginine. However, there was a significant difference between the
      two patient groups and the control group characterized by an impaired GH response
      in the subfertile patients. Serum FSH and serum GH-binding protein were
      significantly higher in the patient groups compared with the controls. Serum LH,
      PRL, T, E2, and IGF-I were similar in all three groups. CONCLUSIONS: This study
      demonstrates that subfertile men may suffer from relative GH insufficiency, which
      could have therapeutical implications.

PMID- 8557136
TI  - Seminal fluid antisperm antibodies measured by direct flow cytometry do not
      correlate with those measured by indirect flow cytometry, the indirect immunobead
      test, and the indirect mixed antiglobulin reaction.
AB  - OBJECTIVE: To compare the direct flow cytometric (FCM) measurement of sperm-bound
      antibodies with the indirect FCM measurement of unbound antisperm antibodies in
      seminal plasma of the same ejaculates. To compare the FCM measurements with the
      indirect mixed antiglobulin reaction (MAR) and the indirect immunobead test (IBT)
      performed on the same seminal plasmas. SETTING: University hospital-based
      infertility service. PATIENTS: Eleven infertile men with a positive
      immunoglobulin (Ig) G direct MAR test and antibody positivity on the direct FCM
      measurements. Four control patients with a negative IgG-direct MAR test. MAIN
      OUTCOME MEASURES: The proportion of spermatozoa positive for IgG and IgA
      antibodies as measured by various tests. RESULTS: The direct and indirect FCM
      measurements for sperm-bound antibodies from seminal plasma did not correlate
      with each other. In general, IgG antibodies were not detectable by indirect FCM
      whereas IgA were detected in lower proportions than by direct FCM measurements.
      Weak correlation was observed between the indirect FCM, indirect MAR, and
      indirect IBT measurements. CONCLUSION: Nearly all of the IgG and some of the IgA
      antisperm antibodies in seminal fluid bind to spermatozoa. Thus, indirect tests
      to measure antisperm antibodies from seminal plasma are likely to miss the
      presence of antisperm IgG antibodies while detecting some cases of IgA
      antibodies.

PMID- 8557137
TI  - Beneficial effects of electrical stimulation before round spermatid nuclei
      injections into rabbit oocytes on fertilization and subsequent embryonic
      development.
AB  - OBJECTIVE: To evaluate the effects of electrical stimulation of rabbit oocytes
      before round spermatid nuclear injection procedure on oocyte activation and
      fertilization. DESIGN: The ratio of activated oocytes to the number of
      successfully injected oocytes and the proportion of offspring to the number of
      activated oocytes after round spermatid nuclear injections into oocytes
      stimulated via mechanical stimulation (group A) or a combination of electrical
      and mechanical stimulation (group B) was compared. INTERVENTIONS: Round spermatid
      nuclei were isolated from mature male rabbits and microinjected into the oocytes
      of groups A and B. Injected oocytes were cultured for 24 hours. The embryos
      developed from groups A and B were transferred to synchronized recipient does.
      RESULTS: Embryos that developed normally through implantation in groups A and B
      were carried successfully through complete gestation in the recipient does. The
      ratio of the activated oocytes to the number of successfully injected oocytes and
      the proportion of offspring to the number of activated oocytes were significantly
      higher in group B. CONCLUSION: Electrical stimulation of oocytes before ooplasmic
      spermatid nuclear injections and ET procedures has beneficial effects on oocytes
      activation, fertilization, and subsequent embryonic development.

PMID- 8557138
TI  - Danazol versus a gonadotropin-releasing hormone agonist as preoperative
      preparation for hysteroscopic metroplasty.
AB  - OBJECTIVE: To compare the efficacy of danazol and a GnRH agonist as preoperative
      preparation for hysteroscopic metroplasty in women with septate uterus. DESIGN:
      Prospective randomized clinical study. SETTING: Tertiary care center. PATIENTS:
      Thirty patients with septate uterus. INTERVENTIONS: The patients were randomized
      to treatment with danazol 600 mg/d for 2 to 4 weeks (n = 15) or with leuprolide
      acetate depot 3.75 mg for 2 months (n = 15) as preoperative therapy for
      hysteroscopic metroplasty. MAIN OUTCOME MEASURES: At the intervention the
      hysteroscopist evaluated difficulty in dilation of the cervical canal, presence
      of endometrial fragments, bleeding, difficulty in maneuvering the resectoscope,
      and operating time. RESULTS: Both the treatments were well tolerated. Metroplasty
      was simpler overall in the danazol group and also faster in introducing the
      resectoscope through the cervical canal and maneuvering it in the uterine cavity
      were both easier. Bleeding was modest in both groups and the anatomic outcome of
      the operation was similar. CONCLUSION: Short preoperative preparation with
      danazol results in favorable operating conditions at limited costs with minimal
      side effects.

PMID- 8557139
TI  - Ovarian maldescent.
AB  - OBJECTIVE: To describe and assess the incidence and impact of ovarian maldescent
      in infertile women. DESIGN: Observational clinical study. SETTING: Referral
      infertility practice. PATIENTS: Women undergoing operative intervention as part
      of infertility evaluation or treatment. INTERVENTIONS: Anatomic observation at
      laparoscopy or laparotomy. RESULTS: Failure of the gonad to descend into the true
      pelvis occurred in 5 of 2,025 operative observations of patients evaluated and
      treated for infertility. Inappropriate descent of the ovary is associated with a
      short infundibulopelvic ligament and attachment of the superior pole of the ovary
      above the pelvic brim adjacent to the fimbriated end of an elongated, ipsilateral
      fallopian tube. It may be bilateral or unilateral and sometimes is associated
      with Mullerian duct abnormalities. CONCLUSIONS: The incidence of ovarian
      maldescent is low, its relationship to infertility is unclear, and it does not
      necessarily preclude conception when other infertility factors are recognized and
      treated. Its rarity and altered anatomy has the potential for therapeutic
      misadventure at laparoscopy, laparotomy, and IVF oocyte retrieval.

PMID- 8557140
TI  - In situ and invasive cervical carcinoma in a cohort of infertile women.
AB  - OBJECTIVE: To assess the risk of cervical neoplasia associated with the use of
      ovulation-inducing agents such as clomiphene citrate (CC) DESIGN: Case-cohort
      study. SETTING: Infertility clinics in Seattle, Washington. PATIENTS: A cohort of
      3,837 women evaluated for infertility at some time during 1974-1985. MAIN OUTCOME
      MEASURE: Computer linkage with a population-based tumor registry was used to
      identify women diagnosed with cervical cancer before January 1, 1992. Data
      regarding infertility testing and treatment were abstracted from medical records
      for women who developed cancer and a randomly selected subcohort. RESULTS: Thirty
      six women in the cohort developed in situ or invasive cervical cancer in
      comparison with an expected number of 67.8 cases (standardized incidence ratio =
      0.5, 95% confidence interval [CI] 0.4 to 0.7). Infertile women with fallopian
      tube abnormalities were at an increased risk of cervical cancer relative to women
      whose infertility was believed to be due to other causes. The risk among women
      who had taken CC was reduced relative to infertile women who had not used this
      drug (relative risk = 0.4, 95% CI 0.2 to 0.8). This association was present both
      in women with and without tubal abnormalities. However, the size of the reduction
      in risk was not influenced by duration of use. CONCLUSIONS: The hypothesis that
      use of antiestrogenic agents, such as CC, can lead to a reduced risk of cervical
      neoplasia warrants testing in other studies.

PMID- 8557141
TI  - Laparoscopically assisted transvaginal segmental resection of the rectosigmoid
      colon for endometriosis.
AB  - OBJECTIVE: To compare three methods of segmental lower colon resection for
      treatment of symptomatic intestinal endometriosis. DESIGN: Retrospective case
      study. SETTING: Private practice patients in a rural community hospital.
      PATIENTS: Patients with nodular, invasive rectosigmoid endometriosis requiring
      segmental resection and anastomosis for treatment. Laparotomy patients were
      matched with laparoscopy patients for severity of intestinal endometriosis.
      INTERVENTIONS: Segmental resection of the rectosigmoid colon by laparotomy, by a
      laparoscopic Intracorporeal technique or by a laparoscopically assisted
      transvaginal technique. MAIN OUTCOME MEASURES: Length of surgery, length of
      hospital stay, operating room charges and total hospital charges corrected to
      1995 dollars. RESULTS: Compared with laparotomy segmental colon resection for
      endometriosis, laparoscopic transvaginal segmental resection resulted in a
      shorter length of stay, equivalent operating room charges, and significantly
      lower total hospital charges. The laparoscopic transvaginal technique is much
      faster, safer, and less fatiguing to the surgeon than a total intracorporeal
      technique. CONCLUSIONS: Laparoscopically assisted transvaginal segmental
      rectosigmoid resection for endometriosis is a promising technique that is simpler
      than a laparoscopic intracorporeal segmental resection technique and is less
      costly than a laparotomy segmental resection technique.

PMID- 8557142
TI  - The incidence of fallopian tube patency after transcervical resection of the
      endometrium including rollerball diathermy to the tubal ostia.
AB  - OBJECTIVE: To evaluate the incidence of tubal patency as well as the shape of the
      endometrial cavity after transcervical resection of the endometrium. DESIGN: An
      open observational trial. SETTING: The obstetrics and gynecology unit at a
      district hospital in Norway. PATIENTS: Fifty consecutive patients who had
      undergone treatment for menorrhagia and metrorrhagia by resection of the
      endometrium and coagulation of the tubal ostium were included in the study.
      INTERVENTION: A hysterosalpingogram was performed with a semistiff catheter and
      injection of 20 mL contrast dye 5 to 12 months after transcervical resection of
      the endometrium and fibroids. MAIN OUTCOME MEASURES: Tubal patency and uterine
      cavity morphology. RESULTS: Forty-four patients showed total occlusion of the
      fallopian tubes, and the uterine cavity showed fibrosis and narrowing of the
      cavity. Three patients showed bilateral and three patients unilateral tubal
      patency. CONCLUSION: Shrinkage and fibrosis of the uterine cavity occur after
      endometrial resection. A significant number of women after transcervical
      resection of the endometrium have patient tubes (13%) despite coagulation of the
      tubal ostia.

PMID- 8557143
TI  - Luteal phase defects and tubal transport.

PMID- 8557144
TI  - The destiny of supernumerary embryos?

PMID- 8557145
TI  - Methotrexate: local versus intramuscular.

PMID- 8557146
TI  - Autoantibodies and embryo implantation rates.

PMID- 8557147
TI  - Autoantibodies and embryo implantation rates.

PMID- 8557149
TI  - Gonadotropin-releasing hormone agonist plus estrogen-progestin "add-back" therapy
      for endometriosis-related pelvic pain.

PMID- 8557148
TI  - Temporolimbic epilepsy and polycystic ovary syndrome.

PMID- 8557150
TI  - Treatment of endometriosis with the antiprogesterone mifepristone (RU486)
AB  - OBJECTIVE: To evaluate the safety and efficacy of an antiprogesterone
      (mifepristone, RU486; Roussel-Uclaf, Romaineville, France) on endometriosis.
      DESIGN: An open, prospective clinical trial. SETTING: The clinical practice of an
      academic faculty. PATIENTS: Nine women with endometriosis were studied.
      INTERVENTIONS: RU486 (50 mg/d) was administered for 6 months. MAIN OUTCOME
      MEASURES: Daily symptom inventories and urinary steroid metabolites were assessed
      before, during, and after treatment. Blood for hormone analysis was obtained
      weekly for 4 weeks and monthly thereafter. The extent of endometriosis, bone
      mineral density, circadian rhythm of cortisol, and LH pulsatility were determined
      before and after treatment. Safety laboratory measurements were made before and
      at 1, 2, and 6 months of treatment. RESULTS: Pelvic pain and uterine cramping
      improved in all patients. Endometriosis regressed by 55%. All patients exhibited
      endocrine features of anovulatory amenorrhea without hypoestrogenism. A rise in
      serum LH and T levels was observed during the first month of treatment and one
      patient developed an elevation of liver transaminases during the last month of
      treatment. All other measurements were unchanged. CONCLUSION: RU486 appears to be
      effective in improving the symptoms and causing regression of endometriosis in
      the absence of significant side effects.

PMID- 8557151
TI  - Medroxyprogesterone acetate supplementation diminishes the hypoestrogenic side
      effects of gonadotropin-releasing hormone agonist without changing its efficacy
      in endometriosis.
AB  - OBJECTIVE: To examine the effects of concomitant use of goserelin and
      medroxyprogesterone acetate (MPA) in the treatment of endometriosis. DESIGN:
      Thirty-eight women with laparoscopically confirmed endometriosis were treated
      with once-a-month s.c. injections of goserelin acetate 3.6 mg (Zoladex depot;
      Zeneca Pharmaceutics, Cheshire, United Kingdom) randomly combined with either MPA
      (100 mg daily; n = 19) or a placebo (one tablet daily; n = 19) in a double-blind
      trial. Symptoms and side effects were monitored for a treatment period of 6
      months and a follow-up period of 6 months. Blood and urine samples were collected
      for the assessment of endocrine and biochemical parameters. A second-look
      laparoscopy was performed 6 months after the treatment in 29 women. RESULTS: The
      extent of endometriosis was diminished similarly in both treatment groups, as
      were pelvic symptoms. Fewer women in the MPA group had hot flushes and sweating
      at 3 and 6 months of treatment. Sex hormone-binding globulin decreased in the MPA
      group but not in the placebo group. Consequently, the E2 index (E2/SHBG X 100),
      reflecting the free fraction of E2, fell more in the placebo group than it did in
      the MPA group. The increased urinary excretion of calcium observed during placebo
      treatment was prevented by MPA. CONCLUSION: High-dose MPA combined with a GnRH
      agonist (GnRH-A) diminished some antiestrogenic effects of the agonist. A
      reduction in hypoestrogenic side effects and a possible bone-sparing effect can
      be regarded as beneficial, especially as the good effect of the GnRH-a on
      endometriotic implants and pelvic symptoms prevailed.

PMID- 8557152
TI  - The profound impact of patient age on pregnancy outcome after early detection of
      fetal cardiac activity.
AB  - OBJECTIVE: To evaluate the influence of maternal age on pregnancy loss rates
      after early documentation of fetal cardiac activity by transvaginal ultrasound
      (US) in previously infertile women. DESIGN: Retrospective, observational study.
      SETTING: Tertiary fertility center. PATIENTS: One hundred eighty-six previously
      infertile women 20 to 43 years of age undergoing ovulation induction. MAIN
      OUTCOME MEASURE: We analyzed 201 clinical pregnancies in which cardiac activity
      had been documented by transvaginal US 35 to 42 days after ovulation in a
      previously infertile population treated at a tertiary fertility center. Patient
      age, infertility diagnosis, ovulation induction protocol, and mode of
      insemination were analyzed by chi 2, Fisher's exact test and logistic regression
      analyses. RESULTS: A profound increase in spontaneous abortion rates occurred as
      a function of maternal age in this population (chi 2 for trend = 15.1). A
      spontaneous abortion rate of 2.1% was observed for maternal ages < or = 35 years
      but this rate increased to 16.1% for patients > or = 36 years (odds ratio, 8.72;
      95 percent confidence interval 2.3 to 32.9). A fivefold increase in spontaneous
      abortion rate was observed in women > or = 40 years compared with women 31 to 35
      years (3.8% versus 20.0%. Infertility diagnosis, mode of insemination, and
      ovulation induction protocol were not associated with an increased risk of
      spontaneous abortion. CONCLUSIONS: The incidence of pregnancy loss after
      confirmation of early fetal cardiac activity by transvaginal US is substantially
      greater in infertile patients than previously reported, when considered as a
      function of maternal age. In particular, patients > or = 36 years should be
      counseled that their risk of spontaneous abortion is significant even after fetal
      heart motion is present on transvaginal US. Cautious optimism and greater
      surveillance may be required during the first trimester of pregnancy in these
      women.

PMID- 8557153
TI  - Abdominal myomectomy: results of a simple operative technique.
AB  - OBJECTIVES: To report a simple and safe procedure of abdominal myomectomy and our
      results performing this technique. DESIGN: The operative technique comprises the
      incision on the most prominent part of the myoma, the use of a hooked clamp to
      hold the tumor, and a surgical knife to peel it, without removing the apparent
      excess of myometrium or serosa. SETTING: University Medical Centers and private
      practice. PATIENTS: Eighty patients, 9 of whom were operated between 10 and 26
      weeks of pregnancy, 3 during cesarean section, and 22 others who had infertility.
      RESULTS: Myomectomy was performed successfully in all patients for whom it was
      scheduled. Eight of nine pregnant patients had successful deliveries at term. The
      cumulative 10-year reoccurrence and reoperation rates of life-table analysis were
      38% and 18%, respectively. The cumulative conception rates were 100% for
      otherwise unexplained infertility at 2 years, and 63% and 79% at 5 years for all
      infertile and all patients attempting conception after myomectomy, respectively.
      An age > 30 years, infertility > 3 years, and multiple fibroids negatively
      affected these rates, whereas the use of an absorbable adhesion barrier
      (Interceed; Johnson & Johnson AB, Somerville, NJ) had a positive effect.
      CONCLUSIONS: This procedure is an appropriate alternative for most women who want
      to preserve or enhance fertility potential, and if necessary, for pregnant women.

PMID- 8557154
TI  - Studies on the cytogenetic and endocrinologic background of spontaneous abortion.
AB  - OBJECTIVE: To determine whether chronic menstrual irregularity with elevated LH
      levels has a role in spontaneous abortion. DESIGN: In 41 consecutively examined
      women with spontaneous abortions occurring within 11 complete gestational weeks,
      fetal chromosomal analyses were performed. The differences of endocrinologic
      background in relation to the result of fetal chromosomal analyses were
      investigated. MAIN OUTCOME MEASURES: Endocrinologic profiles, including menstrual
      history, basal hormone levels (LH, FSH, and PRL), ovarian morphology on
      ultrasound, and fetal chromosomal karyotypes. RESULTS: The women with normal
      fetal karyotypes compared with those with abnormal fetal karyotypes showed higher
      frequency of menstrual irregularity (47.1% versus 8.3%), elevated basal LH levels
      (7.42 +/- 5.12 versus 4.41 +/- 1.39 mIU/mL; conversion factor to SI unit, 1.00),
      and higher frequency of polycystic ovary (41.2% versus 8.3%). CONCLUSION:
      Elevated LH-polycystic ovary may be involved in the genesis of spontaneous
      abortions that are not explainable by fetal chromosomal abnormality.

PMID- 8557155
TI  - Serum free testosterone in polycystic ovary syndrome measured with a new
      reference method.
AB  - OBJECTIVE: To quantify the actual serum free T with a specific new reference
      method in women with polycystic ovary syndrome (PCOS) and to analyze the effects
      of serum free T, total T, and the T:sex hormone-binding globulin (SHBG) ratio on
      the diagnosis of PCOS. SETTING: Outpatient clinic of reproductive endocrinology
      at Turku University Central Hospital, Turku, Finland. PATIENTS: Forty-four
      oligomenorrheic women with PCOS and 26 weight-matched control women with regular
      menstrual cycles. MAIN OUTCOME MEASURES: The concentrations of free T, total T,
      androstenedione (A), LH, FSH, SHBG, and insulin in serum. RESULTS: The mean
      concentrations of free T, total T, A, and LH as well as the LH:FSH and T:SHBG
      ratios were higher, whereas the mean concentrations of FSH was lower in the women
      with PCOS than in healthy women. No differences were found in the free T, total
      T, or T:SHBG levels or in the body mass indexes (BMIs) between the hirsute (n=26)
      and nonhirsute (n = 18) women with PCOS. Both elevated free T concentrations and
      high T:SHBG ratios were associated with obesity, but serum total T was
      independent of BMI. The serum free T measurement discriminated PCOS women from
      controls to a similar extent as total T and T:SHBG ratio as judged by a receiver
      operating characteristics analysis. CONCLUSIONS: The present data indicate that
      determination of free T provides little additional information in the diagnosis
      of hirsutism or PCOS and does not have to be included to the basic evaluation of
      these patients. Only half of women with PCOS exhibited elevated serum free T
      concentrations.

PMID- 8557156
TI  - Clinical and hormonal effects of gonadotropin-releasing hormone agonist plus an
      oral contraceptive in severely hirsute patients with polycystic ovary disease.
AB  - OBJECTIVE: To evaluate the therapeutic effects of a GnRH agonist (GnRH-a),
      leuprolide acetate (LA) plus a pill containing ethinyl E2 plus cyproterone
      acetate (CPA) in a group of women with severe hirsutism who were unresponsive to
      oral contraceptive (OC) therapy. DESIGN: Twenty-four patients suffering from
      severe hirsutism secondary to polycystic ovary disease (PCOD) were treated for 12
      months with 3.75 mg IM LA every 28 days in association with 0.035 mg/d ethinyl E2
      plus 2 mg/d CPA (Diane; Schering, Berlin, Germany) for 21 d/mo. SETTING: Patients
      were recruited in the Institute of Obstetrics and Gynecology, St. Bambino
      Hospital, University of Catania, Catania, Italy. Hormonal assays were performed
      in the Hormone Laboratories of St. Bambino Hospital, University of Catania,
      Catania, Italy. MAIN OUTCOME MEASURES: Every 3 months the hirsutism score was
      evaluated. Mean serum concentrations of LH, FSH, E2, total and free T,
      androstenedione (A), sex hormone-binding globulin (SHBG), and DHEAS were
      determined. Every 6 months a vaginal ultrasound examination was performed.
      RESULTS: In all patients after 6 and 12 months of treatment with LA plus OC, the
      hirsutism score improved significantly. Serum levels of LH, FSH, E2, total and
      free T, A, and DHEAS decreased significantly, whereas SHBG showed a marked
      increase. A significant reduction in the ovarian size was observed. CONCLUSION:
      Gonadotropin-releasing hormone agonist, associated with a pill containing CPA,
      reduced the hirsutism in severely affected women with PCOD who are unresponsive
      to OC treatment alone.

PMID- 8557158
TI  - Endometrial cell adhesion in an in vitro model using intact amniotic membranes.
AB  - OBJECTIVE: To study adhesion between endometrial tissue and peritoneum using
      intact amniotic membranes as an in vitro model. DESIGN: A cell biologic and
      immunohistochemical study. SETTING: Tertiary-care university medical center.
      PATIENTS: Ten patients with regular and ovulatory cycles. INTERVENTIONS:
      Mechanically dissected tissue fragments from endometrial biopsies were cultured
      on either side of intact amniotic membranes. Also, the carcinoma cell lines RL95
      2 and AN3CA were used. MAIN OUTCOME MEASURES: The adhesion of endometrial
      fragments and of endometrial carcinoma cell lines to amniotic membrane was
      studied in vitro and evaluated using frozen sections. The composition of the
      extracellular matrix and the presence of intermediate filament proteins of
      amniotic membrane were determined using immunohistochemistry and compared with
      those of normal peritoneum. RESULTS: Peritoneum and amniotic membrane were
      similar with respect to expression of cytokeratins in epithelial lining and of
      extracellular matrix (ECM) components. The endometrial fragments did not adhere
      to the intact epithelial side of the amniotic membrane. In contrast, adhesion did
      occur to the nonepithelial side of the amnion. The carcinoma cell lines RL95-2
      and AN3CA adhered to either side of intact amniotic membranes. CONCLUSIONS: An
      intact epithelial lining prevents adhesion of endometrial fragments to the ECM of
      amniotic membranes in vitro. An intact epithelium could be important defense
      mechanism in preventing initial adhesion of retrogradely shed endometrium
      fragments to peritoneum.

PMID- 8557159
TI  - Regulation of corpus luteum function in early human pregnancy.
AB  - OBJECTIVE: To investigate the capacity of the human corpus luteum (CL) of
      pregnancy to form cyclic adenosine-3',5'-monophosphate (cAMP) and P in vitro in
      response to hCG and prostaglandin (PG) E2. DESIGN: Six women undergoing
      sterilization concomitant with legal abortion and eight women undergoing surgery
      for ectopic pregnancy were included. Human chorionic gonadotropin was analyzed
      preoperatively in two serum samples. The CL were excised and luteal specimens
      were incubated for 2 hours in the presence or absence of hCG or PGE2. The tissue
      concentrations of cAMP and P concentrations in the incubation media were
      measured. The in vitro results were correlated to the preoperative daily change
      in serum hCG. RESULTS: In CL from pregnancies with normally rising serum hCG
      levels, the addition of hCG in vitro did not affect luteal cAMP or P production.
      In pregnancies with plateauing and/or decreasing serum hCG levels, the addition
      of hCG in vitro significantly stimulated cAMP and P formation, and this
      stimulatory effect correlated significantly with the preoperative daily change in
      serum hCG. In contrast to hCG, PGE2 had the same stimulatory effect in vitro on
      CL specimens from both normal and pathological pregnancies. This effect did not
      correlate with the preoperative daily change in serum hCG. CONCLUSIONS:
      Prostaglandin E2 stimulates all CL, irrespective of any changes in preoperative
      serum hCG levels. In contrast, the stimulatory effect of hCG in vitro does not
      correlate with changes in serum hCG, and thus CL from pregnancies with normally
      rising serum hCG levels are refractory to hCG in vitro.

PMID- 8557157
TI  - Hypogonadism in Rhodesian sleeping sickness: evidence for acute and chronic
      dysfunction of the hypothalamic-pituitary-gonadal axis.
AB  - OBJECTIVE: To investigate acute and long-term effects of Rhodesian sleeping
      sickness on the function of the hypothalamic-pituitary-gonadal (HPG) axis in men.
      DESIGN: An observational, cross-sectional study. SETTING: Primary health care
      centers under care of the National Sleeping Sickness Control Program in southeast
      Uganda. PARTICIPANTS: Fifty-two male patients with sleeping sickness at different
      stages of treatment and 11 clinically healthy male volunteers recruited from
      health care personnel. INTERVENTIONS: Patients and controls were questioned about
      loss of libido and impotence. All received 100 micrograms GnRH i.v. Blood was
      drawn before and 30 minutes after GnRH administration. MAIN OUTCOME MEASURES:
      Frequency of loss of libido and impotence. Baseline T and sex hormone-binding
      globulin baseline and GnRH- stimulated serum LH and FSH concentrations. RESULTS:
      Loss of libido and/or impotence were present in 39% of men with active disease
      before therapy, whereas 84% were biochemically hypogonadal. After cure, 45% of
      men still were symptomatic and 45% were biochemically hypogonadal. Compared with
      controls (806 +/- 59 pg/mL [conversion factor to SI unit, 0.03467]; mean +/-
      SEM), T concentrations were decreased substantially in patients before (249 +/-
      48 ng/dL), during treatment (429 +/- 56 ng/dL), and after cure (431 +/- 58
      ng/dL). Corresponding baseline LH concentrations were inappropriately low and the
      relative LH response to GnRH was reduced both before and during treatment (794%
      +/- 131% versus 322% +/- 68%). Follicle-stimulating hormone concentrations
      increased gradually up to 8.0 +/- 1.3 mIU/mL (conversion factor to SI unit, 1.00)
      at the end of treatment, returning to 4.2 +/- 0.6 mIU/mL after cure. CONCLUSIONS:
      Rhodesian sleeping sickness causes acute and chronic HPG axis dysfunction. The
      clinical and biochemical picture suggest a combined central and peripheral
      hypogonadism. This is only in part reversible after cure and most likely due to
      direct parasitic infiltration and/or secondary inflammation causing necrosis
      and/or fibrosis at the pituitary and gonadal levels.

PMID- 8557160
TI  - The effect of insulin and insulin-like growth factors on the expression of
      steroidogenic enzymes in a human ovarian thecal-like tumor cell model.
AB  - OBJECTIVE: To determine the effects of insulin and insulin-like growth factors
      (IGF-I and IGF-II) on steroidogenesis and steroidogenic enzyme expression in a
      human ovarian thecal-like tumor cell culture model system. DESIGN: Human ovarian
      thecal-like tumor cells treated with forskolin and insulin IGF-I or IGF-II were
      evaluated for media accumulation of P and androstenedione (A) as well as 3 beta
      hydroxysteroid dehydrogenase (3 beta HSD) and cytochrome P450 17 alpha
      hydroxylase (P450c17) enzyme activity. Northern analysis of cytochrome P450 side
      chain cleavage (P450scc), P450c17, and 3 beta HSD messenger RNA (mRNA) also was
      performed. RESULTS: Basal hormone secretion, enzyme activity, and mRNA levels
      were not affected by treatment with insulin or the IGFs. Forskolin treatment
      stimulated steroid production, enzyme activity, and mRNA content. Forskolin
      stimulated P secretion was augmented 30% by treatment with insulin and IGFs,
      whereas 3 beta HSD activity was augmented twofold to threefold. Forskolin
      stimulated A and P450c17 activity were enhanced by treatment with insulin and the
      IGFs. In forskolin-treated cells. P450c17 and P450scc mRNA levels were not
      affected by insulin (100 nM) or IGF (10 nM) treatment; however, 3 beta HSD mRNA
      levels were augmented by treatment with insulin and IGFs. CONCLUSIONS: We
      observed that forskolin-stimulated human ovarian thecal-like tumor cell
      steroidogenesis, P450c17, and 3 beta HSD activity, as well as mRNA content for
      P450scc, 3 beta HSD, and P450c17. Insulin and the IGFs augmented forskolin
      stimulated production of P and the expression of 3 beta HSD, with little effect
      on A production, P450scc, or P450c17 expression.

PMID- 8557161
TI  - Oocyte donation program: pregnancy and implantation rates in women of different
      ages sharing oocytes from single donor.
AB  - OBJECTIVE: To investigate the importance of uterus age as regards of pregnancy,
      implantation, and abortion rates using the oocyte donation model. DESIGN:
      Retrospective data analysis of cases where recipients of different ages shared
      oocytes from single donor. SETTING: A tertiary infertility center. PATIENTS: One
      hundred fourteen women (21 to 49 years of age) undergoing a total of 114 cycles
      of oocyte donation were divided into two groups according to age (group A < = or
      39 years: group B between 40 and 49 years). INTERVENTIONS: Hormonal replacement
      therapy was given using increasing doses of 17 beta-E2 (2, 4, and 6 or 8 mg) and
      either 100 mg of P in oil or 600 mg of micronized P through the vaginal route.
      MAIN OUTCOME MEASURES: Pregnancy, abortion, and implantation rates. RESULTS:
      Fifty-seven transfer cycles were performed per age group. Twenty-seven clinical
      pregnancies were achieved in Group A and 14 in group B, with pregnancy rates
      (PRs) of 47.3% and 24.5%, respectively. There were four abortions in group A and
      one in group B, resulting in abortion rates of 14.8% and 7%, respectively. Thirty
      four of 137 transferred embryos in group A and 20 of 134 in group B implanted,
      resulting in implantation rates of 24.8% and 14.9%, respectively. CONCLUSION:
      This study seems to suggest that there are differences in pregnancy and
      implantation rates in recipients of different ages because of uterine
      receptivity. Fertility therefore does not depend merely on oocyte age and quality
      but also on uterine age.

PMID- 8557162
TI  - Success of donor oocyte in in vitro fertilization-embryo transfer in recipients
      with and without premature ovarian failure.
AB  - OBJECTIVE: To compare the effectiveness of donor oocyte in IVF-ET in patients
      with premature ovarian failure (POF) versus those (non-POF) with other
      indications for donor oocyte IVF-ET. DESIGN: Retrospective comparative clinical
      study. SETTING: University-based IVF-ET facility. PATIENTS: Eighty-six donor
      oocyte IVF-ET cycles from 32 POF patients (39 cycles) and 38 non-POF patients (47
      cycles). INTERVENTIONS: Fertile oocyte donors, age 19 to 38 years, were given
      luteal phase GnRH agonist, gonadotropins, and HCG. Recipients were given
      transdermal 17 beta-E2 and P in oil. MAIN OUTCOME MEASURES: Donor and recipient
      age, characteristics of controlled ovarian hyperstimulation, oocytes retrieved,
      embryos frozen and transferred, and percentage with male factor infertility,
      fertilization rate, implantation rate, and clinical pregnancy rate (PR) per cycle
      and per transfer. RESULTS: Given limitations of sample size, there were no
      detectable differences in clinical PR per cycle and per transfer, fertilization
      rate, and implantation rate between POF and non-POF groups despite recognizable
      differences in recipient age and degree of male factor infertility. CONCLUSIONS:
      Donor oocyte IVF-ET success rates were not different in patients with and without
      POF. Age-related changes in oocyte quality, rather than uterine senescence, is a
      major factor for the age-related decline in fertility.

PMID- 8557163
TI  - Confirmation of a clinical diagnosis of Prader-Willi syndrome by fluorescence in
      situ hybridization (FISH).

PMID- 8557164
TI  - Asthma and the beta 2-agonist controversy: much ado about something.

PMID- 8557165
TI  - The need for an improved judicial system.

PMID- 8557166
TI  - The Delaware Foundation for Health Care--history revisited.

PMID- 8557167
TI  - Home healthcare: a risky business.

PMID- 8557168
TI  - The history of neuropeptides 1.

PMID- 8557169
TI  - Proteolytic processing mechanisms in the biosynthesis of neuroendocrine peptides:
      the subtilisin-like proprotein convertases.
AB  - The recent discovery of a novel family of precursor processing endoproteases has
      greatly accelerated progress in understanding the complex mechanisms underlying
      the maturation of prohormones, neuropeptides, and many other precursor-derived
      proteins. At least six members of this family have been found thus far in
      mammalian species, several having alternatively spliced isoforms, and related
      enzymes have been identified in many invertebrates, including molluscs, insects,
      nematodes, and coelenterates. The proprotein convertases are all dependent on
      calcium for activity and all possess highly conserved subtilisin-like domains
      with the characteristic catalytic triad of this serine protease (ordered Asp,
      His, and Ser along the polypeptide chain). Two members of this family, PC2 (SPC2)
      and PC1/PC3 (SPC3), appear to play a preeminent role in neuroendocrine precursor
      processing. Both convertases are expressed only in the brain and in the extended
      neuroendocrine system, while another important family member--furin/PACE (SPC1)-
      is expressed more ubiquitously, in almost all tissues, and at high levels in
      liver. SPC2 and SPC3 exhibit acidic pH optima and other properties which enhance
      their activity in the acidic, calcium-enriched environment of the dense-core
      secretory granules of the regulated pathway in neuroendocrine cells, while furin
      has a neutral pH optimum and is localized predominantly to the trans Golgi
      network where it is retained by a C-terminal transmembrane domain. Furin
      processes a wide variety of precursors in the constitutive pathway, such as those
      of growth factors, receptors, coagulation factors, and viral glycoproteins.
      Recent findings on the processing of proopiomelanocortin, proinsulin,
      proglucagon, and several other neuroendocrine precursors by SPC2 and SPC3 are
      discussed, along with information on the structure, properties, evolution,
      developmental expression, and regulation of the convertases. An inherited defect
      in the fat/fat mouse which affects the processing of proinsulin, and probably
      also many other prohormones, due to a point mutation in carboxypeptidase E has
      recently been identified and has begun to provide new insights into the
      functional integration of the individual processing steps.

PMID- 8557170
TI  - Corticotropin releasing factor (CRF) binding protein: a novel regulator of CRF
      and related peptides.
AB  - A 37-kDa corticotropin releasing factor (CRF) binding protein (CRF-BP) was
      purified from human plasma by repeated affinity purification and subsequently
      sequenced and cloned. The human and rat CRF-BP cDNAs encode proteins of 322 amino
      acids with one putative signal sequence, one N-glycosylation site, and 10
      conserved cysteines. Human CRF-BP binds human CRF with high affinity but has low
      affinity for the ovine peptide. In contrast, sheep CRF-BP binds human and ovine
      CRF with high affinity. The CRF-BP gene consists of seven exons and six introns
      and is located on chromosome 13 and loci 5q of the mouse and human genomes,
      respectively. CRF-BP inhibits the adrenocorticotrophic hormone (ACTH) releasing
      properties of CRF in vitro. CRF-BP dimerizes after binding CRF and clears the
      peptide from blood. This clearance mechanism protects the maternal pituitary
      gland from elevated plasma CRF levels found during the third trimester of human
      pregnancy. CRF-BP is expressed in the brains of all species so far tested but is
      uniquely expressed in human liver and placenta. In brain, CRF-BP is membrane
      associated and is predominantly expressed in the cerebral cortex and subcortical
      limbic structures. In some brain areas CRF-BP colocalizes with CRF and CRF
      receptors. The protein is also present in pituitary corticotropes, where it is
      under positive glucocorticoid control, and is likely to locally modulate CRF
      induced ACTH secretion. The ligand requirements of the CRF receptor and the CRF
      BP can be distinguished in that central human CRF fragments, such as CRF (6-33)
      and CRF (9-33), have high affinity for CRF-BP but low affinity for the CRF
      receptor. The binding protein's ability to inhibit CRF-induced ACTH secretion can
      be reversed by CRF (6-33) and CRF (9-33), suggesting that ligand inhibitors may
      have utility in elevating free CRF levels in disease states associated with
      decreased CRF. Thus, by controlling the amount of free CRF which activates CRF
      receptors, it is likely that the CRF-BP is an important modulator of CRF both in
      the CNS and in the periphery.

PMID- 8557171
TI  - Functional pleiotropy of the neurohormone melatonin: antioxidant protection and
      neuroendocrine regulation.
AB  - The pineal hormone melatonin exhibits remarkable functional versatility. Shortly
      after its discovery, melatonin was functionally linked to the regulation of the
      neuroendocrine axis, particularly to the reproductive system. However, judging
      from the wide variety of cellular changes that occurred following either
      pinealectomy, to remove the primary source of melatonin, or the exogenous
      administration of the indole, it was obvious that the activity of melatonin far
      transcended its actions on the hypothalamo-pituitary-gonadal system. Roughly 30
      months ago it was discovered that melatonin is a highly efficient free radical
      scavenger and general antioxidant. This implied that melatonin, which is both
      lipophilic and hydrophilic, has effects not only in every cell but also within
      every subcellular compartment. These intracellular actions of melatonin, some of
      which are independent of any receptor interaction and some of which are mediated
      by nuclear receptors, have become the focus of much of the current investigation.
      As an antioxidant, melatonin has been shown in vitro to be a highly efficient
      scavenger of the very reactive and toxic hydroxyl radical. Indeed, on an
      equimolar basis melatonin proved significantly more efficient in neutralizing the
      hydroxyl radical than did the two well-known scavengers, glutathione and
      mannitol. Likewise, melatonin was found to also scavenge the peroxyl radical
      which is generated during lipid peroxidation; in this regard it was roughly twice
      as effective as vitamin E (alpha-tocopherol). The antioxidant activities of
      melatonin have been well documented in tissue homogenates and organisms as well.
      When rats are treated with the chemical carcinogen safrole, this agent induces
      the generation of free radicals which in turn extensively damage nuclear DNA;
      this damage is almost totally eliminated if the animals are cotreated with
      melatonin. Also, damage to DNA in human lymphocytes due to ionizing radiation,
      another treatment which is known to induce free radical formation, is greatly
      reduced if the cells are treated with melatonin prior to radiation. Cytosolic
      protein seems also to be protected from free radical damage when melatonin is
      present. When newborn rats are treated with a glutathione-depleting drug at
      birth, by 2 weeks of age the animals have cataracts. Cataracts form because
      oxidants damage protein in the presence of low intracellular levels of
      glutathione. Cataracts induced by this means are essentially prevented if the
      glutathione-depleted rats are supplemented with melatonin. Finally, membrane
      lipid peroxidation, induced either in vivo or in vitro by any of several means,
      all of which involve free radicals, is drastically attenuated in the presence of
      melatonin. Considering melatonin's ability to cross all morphophysiological
      barriers and to enter every cell, and all subcellular compartments, the
      implication is that this indole may play a very important role in the
      antioxidative defense system of the organism. These findings potentially have
      important implications for a wide variety of age-related diseases and to aging
      itself. Melatonin's control of reproductive physiology in photoperiodic mammals
      is well documented. However, the site of interaction of melatonin with the
      neuroendocrine axis has been especially difficult to determine. The discovery and
      cloning of a membrane melatonin receptor on neurosecretory cells in the
      hypothalamus and on hormone secreting cells of the anterior pituitary gland
      stimulated a great deal of investigation which has failed to prove the
      involvement of these receptors in the processes by which melatonin influences
      reproductive physiology. The recent identification of nuclear melatonin receptors
      as well as the nonreceptor-mediated actions of the indole are currently being
      examined as to their association with reproductive function.

PMID- 8557172
TI  - Steroids, stability and stress.

PMID- 8557173
TI  - Augmented prenatal visual stimulation alters postnatal auditory and visual
      responsiveness in bobwhite quail chicks.
AB  - This study examined whether previously reported effects of altered prenatal
      sensory experience on subsequent acceleration of intersensory development in
      precocial birds are mediated by mechanisms sensitive to the overall amount of
      stimulation provided. Results revealed that bobwhite quail chicks exposed to
      substantially augmented amounts of prenatal visual stimulation show altered
      patterns of species-typical perceptual development. Specifically, chicks
      continued to respond to maternal auditory cues into later stages of postnatal
      development and failed to demonstrate responsiveness to maternal visual cues.
      Embryos also failed to demonstrate prenatal auditory learning of an individual
      maternal call, a behavior reliably seen in unmanipulated embryos. These findings
      suggest that substantially increased amounts of prenatal sensory stimulation can
      interfere with the emergence of species-typical patterns of postnatal
      intersensory functioning and lend support to the notion that sensory stimulation
      that falls within some optimal range maintains or facilitates normal patterns of
      perceptual development, whereas stimulation beyond the range of the species norm
      can result in intersensory interference.

PMID- 8557174
TI  - Testosterone-induced shortening of the storage phase of song development in birds
      interferes with vocal learning.
AB  - Bird song is a complex, learned behavior. Vocal learning in sparrows involves
      several different processes that occur in a distinct temporal pattern over the
      course of the first year of life. Songs are acquired without practice during a
      sensitive period within the first 3 months of life and rehearsal of the acquired
      song does not begin until 7 or 8 months of age. The function of the storage
      period between song acquisition and production is not known. We set out to
      investigate its significance by administering testosterone, known to stimulate
      production of adult song, to birds at 100 days of age after song acquisition was
      completed but some 5 months prior to normal song onset. Most testosterone-treated
      birds produced abnormal songs resembling those of males raised in acoustic
      isolation suggesting that, in sparrows, events occurring during the storage phase
      play a significant role in vocal learning.

PMID- 8557175
TI  - Contributions of experience to the development of musical processing in infancy.
AB  - Full-term infants' performance in detection of melodic alterations appeared to be
      influenced by perceptual experience from 6 months to 1 year of age, and an
      experiment with infants born prematurely supported the hypothesis that experience
      affects music processing in infancy. These findings suggest parallel
      developmental tendencies in the perception of music and speech that may reflect
      general acquisition of perceptual abilities for processing of complex auditory
      patterns. This acquisition may contribute to the cultural enfranchisement of
      infants through perceptual experience.

PMID- 8557176
TI  - Responses of infant titi monkeys, Callicebus moloch, to removal of one or both
      parents: evidence for paternal attachment.
AB  - The response to parental separation in infant titi monkeys was evaluated.
      Separation from the mother for 1 hr did not elicit an adrenocortical response
      from the infant unless the father was also removed. Separation from the father
      elicited a significant elevation in adrenocortical activity even when the mother
      remained with the infant during the separation period. Infants showed the highest
      cortisol levels and vocalization rates when both parents were removed and the
      infant remained alone in the living cage for 1 hr. As in previous research,
      infants maintained higher levels of contact with the father than with the mother.
      The results indicate that in this monogamous New World primate, the father is the
      primary attachment figure for the developing infant.

PMID- 8557177
TI  - Variation in HLA-associated risks of childhood insulin-dependent diabetes in the
      Finnish population: I. Allele effects at A, B, and DR loci. DiMe Study Group.
      Childhood Diabetes in Finland.
AB  - Variation in the risk of insulin-dependent diabetes mellitus (IDDM) across
      alleles at HLA-A, B, and DR loci was investigated in a population-based study of
      801 families of children with newly diagnosed IDDM in Finland nationwide.
      Parallel analyses assessed the relative frequencies of alleles in IDDM children
      compared with age-matched sibling controls and with the four possible genotypes
      which could have been inherited from the parents. The joint effects of DR3 and
      DR4 alleles were investigated under dominant, recessive, and additive models of
      gene expression. The additive model gave the best fit, though the relative risk
      for DR4 homozygotes was smaller than predicted. To investigate other alleles, we
      fitted the standard multiplicative model for alleles at each locus. After
      controlling for the correlation among alleles, significantly elevated risks were
      found for B13, DR3, DR4, and DR14. Subjects with these alleles have more than
      twice the risk of IDDM as those without. Alleles A24 and B62 incurred relative
      risks between one and two. DR2 and DR5 were significantly negatively associated
      with IDDM, incurring less than half the risk. These findings support an
      independent role of class I antigens in the etiology of IDDM.

PMID- 8557178
TI  - Variation in HLA-associated risks of childhood insulin-dependent diabetes in the
      Finnish population: II. Haplotype effects. DiMe Study Group. Childhood Diabetes
      in Finland.
AB  - We fitted models for the main effects of alleles at the HLA-A, B, and DR loci and
      their haplotypes on the risk of insulin-dependent diabetes mellitus (IDDM).
      Empirical Bayes methods were used, assuming independent exchangeable normal
      priors for effects at each locus separately and for haplotype effects. A pure
      main effects model, pure haplotype effects model, and a combined model were
      fitted using Gibbs sampling. The main effects model showed that the DR locus had
      the largest variation in risk between alleles, followed by the B locus;
      significance tests for each allele in this model were in general agreement with
      those in the companion paper [Langholz et al. (1995) Genet Epidemiol 12:441-453],
      although all relative risks were shrunk toward 1.0 in the empirical Bayes
      analysis. The variance estimate for pure haplotype effects was substantially
      larger than for any of the three main effects considered in this analysis, but in
      the combined model, the DR locus showed larger variability than the haplotype
      deviations. We confirmed that haplotype A2/B56/DR4 previously reported to be
      common in Finnish diabetics does indeed confer unusually high risk (relative risk
      = 7.6, P < 0.001), but found this to be only 1.9 times higher than predicted by
      its component main effects (P = 0.046). All of the other haplotypes could be
      adequately explained by their main effects. Empirical Bayes methods provide a
      natural means of dealing with the problems of multiple comparisons,
      multicolinearity, and sparse data that complicate the analysis of HLA data.

PMID- 8557179
TI  - Association of childhood rhabdomyosarcoma with neurofibromatosis type I and birth
      defects.
AB  - Rhabdomyosarcoma (RMS) is an uncommon malignant soft tissue sarcoma whose cause
      is largely unknown. Reported risk factors include genetic alterations (e.g., p53
      mutations, a defective gene at 11p15.5, or specific chromosomal translocation of
      t(2:13)), and parents' use of drugs around the time of conception. We present
      results from a national, case-control study of 249 RMS cases (170 males and 79
      females) and 302 controls (196 males and 106 females). The cases, aged 0-20 years
      at diagnosis, were identified via the Intergroup RMS Study-III during 1982-1988.
      Controls were selected by random digit telephone dialing. As a supplement to the
      original study, information on genetic diseases and birth defects (BD) was
      collected from the subjects' parents by telephone interview. Fifty-six (22.5%)
      cases and 55 (18.2%) controls were reported to have genetic diseases or BD (odds
      ratio [OR] = 1.30,95% confidence interval [CI] = 0.85-2.02, P = .21). The case
      group had a significantly higher frequency of neurofibromatosis type I (NF1) than
      did the control group, i.e., five cases (2.0%) had NF1 vs. zero controls (P =
      .02). The case group also had a higher frequency of major BDs than did the
      control group (6.0% vs. 2.6%, OR = 2.36, 95% CI = 0.92-6.52, P = .05). However,
      this excess was only observed in males (7.6% vs. 2.6%, OR = 3.16, 95% CI = 1.02
      10.41, P = .02). Among the 15 cases having both RMS and major BDs, six (40.0%)
      had both conditions in the same regional anatomic site: Two (13.3%) had both in
      the extremities, two (13.3%) in the genitourinary system, and two in the head and
      neck. These findings suggest that common genetic mechanisms or in utero exposures
      may be involved in the development of many childhood tumors and congenital
      abnormalities.

PMID- 8557180
TI  - Major gene with sex-specific effects influences fat mass in Mexican Americans.
AB  - Increased adiposity has repeatedly been identified as a major risk factor for a
      variety of chronic diseases. However, the question still remains whether the
      amount of adipose tissue itself is genetically mediated. To address this
      question, a segregation analysis, using maximum likelihood techniques as
      implemented in the computer program Pedigree Analysis Package (PAP), was
      performed on fat mass (kilograms of body fat) in a large sample of extended
      Mexican American families residing in San Antonio, TX. The only model not
      rejected was a Mendelian mixed model for fat mass, incorporating genotype x sex
      interaction. In males the major gene accounted for 37% of the total variance
      compared with 43% in females. In both sexes homozygous recessive individuals have
      a fat mass more than double that of individuals of the other two genotypes. It
      was possible to reject linkage of the anonymous major gene for fat mass with
      several candidate loci for obesity. However, tentative evidence of linkage was
      detected with markers on both chromosomes 2 and 11, thereby providing hypotheses
      for future testing.

PMID- 8557181
TI  - Underexpression of the apolipoprotein E2 and E4 alleles in the Greek Cypriot
      population of Cyprus.
AB  - Apolipoprotein E (APOE) plays an important role in the multifactorial etiology of
      both cardiovascular disease and Alzheimer's disease. Polymerase chain reaction
      (PCR) was used to investigate the APOE gene polymorphism in 335 unrelated Greek
      Cypriots living on the island of Cyprus. For the most common APOE genotypes, the
      Greek Cypriots followed the general Caucasian European pattern of having higher
      genotypic frequencies of E3/3, followed by E3/4, and then E2/3. Among the
      European populations compared, Greek Cypriots exhibited the lowest relative
      frequency of the E3/4 genotype (12.83%). Also, the relative frequencies of the E2
      and E4 alleles in Greek Cypriots were among the lowest around the world (5.4% and
      7.0%, respectively). This was also demonstrated by using the complete and the
      average clustering methods of analysis where the APOE allele relative frequencies
      in Greek Cypriots were compared to 46 other populations. The Greek Cypriot
      population in these analyses clustered with populations mainly from south Europe
      and Japan which have low E2 and E4 allele frequencies. The Greek Cypriot
      population will be studied further for elucidating the effect(s) and the role of
      APOE in cardiovascular disease and the APOE4 allele as a possible metabolic
      factor affecting the rate of expression of both Alzheimer's disease and vascular
      dementia.

PMID- 8557182
TI  - Apolipoprotein B gene DNA polymorphisms (EcoRI and MspI) and serum lipid levels
      in the Serbian healthy population: interaction of rare alleles and smoking and
      cholesterol levels.
AB  - The frequency of restriction fragment length polymorphisms (RFLPs) of the
      apolipoprotein B (apo B) gene, detected by EcoRI and MspI, and their influence on
      serum lipids were studied in a total of 239 healthy subjects from the Belgrade
      area. The influence of interaction between different genotypes and smoking was
      also studied. The relative frequency of both rare R2 and M2 alleles (lacking the
      cutting site) was similar to that reported in other groups of Caucasians (0.16
      and 0.11, respectively). No association was observed between the apo B genotypes
      and serum lipid levels adjusted for age, body mass index, and blood pressure
      either in the whole sample or in either women or men. When smokers and non
      smokers were considered separately, smoking had a significant impact on total
      cholesterol variability in all individuals with genotype M1M2 and high density
      lipoprotein (HDL) cholesterol variability in women with genotype R1R2. The
      presence of the rare alleles of these two polymorphisms in smokers was associated
      with lower lipid levels in the whole sample and in both women and men analyzed
      separately, except for an increase of HDL cholesterol level in male smokers,
      heterozygous for EcoRI polymorphism (R1R2).

PMID- 8557184
TI  - Maximum-likelihood estimation in linkage heterogeneity models including
      additional information via the EM algorithm.
AB  - In linkage analysis, estimated recombination fractions between a disease gene and
      several markers are used to assign the disease gene to a particular chromosome
      region. For rare diseases, locus heterogeneity leads to different recombination
      fractions in different families, and a set of pedigrees can be regarded as a
      mixture. Information which can help to classify the different families may be
      available and can be included in the model. This is demonstrated for a data set
      of X-linked retinitis pigmentosa families. The joint distribution of the position
      of the disease gene and the additional information on the penetrance of tapetal
      reflex among obligate female carriers is studied. A model including the
      additional information is fitted to the data using the EM algorithm. The
      algorithm uses for every pedigree the lod score curve which can be obtained from
      a standard (multipoint) linkage analysis.

PMID- 8557183
TI  - Recombination fraction estimate of zero in the presence of apparent recombinants:
      effects of incomplete penetrance and sporadic cases.
AB  - For a fully penetrant trait, apparent recombinants between the trait and marker
      loci result in an estimate of the recombination fraction theta > 0. Given
      allowance for reduced penetrance and/or sporadic cases, this no longer need be
      true. In this short communication, we describe conditions under which theta is
      estimated to be zero despite the presence of apparent recombinants. We
      demonstrate that even if a large proportion of unaffected individuals are
      apparent recombinants and the penetrance is moderately high, the lod score may be
      maximized at theta = 0. Despite maximization at theta = 0, presence of apparent
      recombinants reduces the maximum lod score in comparison to its value if no
      apparent recombinants are present.

PMID- 8557185
TI  - Genetic analysis of durations: correlated frailty model applied to survival of
      Danish twins.
AB  - Population studies of changes in human morbidity and mortality require models
      which take into account the influence of genetic and environmental factors on
      life-related durations, such as age at onset of the disease or disability, age at
      death, etc. In this paper we show how a bivariate survival model based on the
      concept of correlated individual frailty can be used for the genetic analysis of
      durations. Six genetic models of frailty are considered and applied to Danish
      twin survival data. The results of statistical analysis allow us to conclude that
      at least 50% of variability in individual frailty is determined by environmental
      factors. The approach suggests a method of estimation of the lower bound for the
      biological limit of human longevity. Directions for further research are
      discussed.

PMID- 8557186
TI  - Relational processes and identity formation in adolescence: the example of A
      Separate Peace.
AB  - The process of identity formation in adolescence, specifically, the relational
      context of identity formation, is examined through the prism of the story of an
      adolescent boy's development during the Second World War at a boarding school in
      New Hampshire, USA--John Knowles's A Separate Peace. The discussion focuses on
      mirroring, on the adolescent's need to be validated and the simultaneous fear of
      transparency, and on idealization and deidealization. Using the book as a
      narrative example of the transformation of connections that are essential to the
      process of development, the authors discuss the complexity of male adolescent
      growth.

PMID- 8557187
TI  - The impact of mood on time perception, memorization, and acceptance of waiting.
AB  - The effects of mood on two cognitive processes, memorization and time perception,
      were examined. Participants (N = 155) first watched videos that successfully
      manipulated their mood (happy or sad); then they watched a video simulating a
      waiting line (Bateson & Hui, 1992; Bosselman & Craik, 1987). A questionnaire was
      administered to both groups to assess the number of items memorized from the
      "waiting" video, the estimated waiting time, and the degree of acceptance of
      waiting time. A series of analyses of variance showed that happy mood enhanced
      the number of items memorized and the acceptance of waiting but had no
      significant effect on time estimates. Memorization had no effect on time
      estimates or on acceptance of waiting; as expected, the longer the perceived
      waiting time, the less the acceptance of waiting time. A global model based on a
      system of linear equations (LINEQS) reproduced these results, which are
      interpreted in terms of both previous studies on mood and time estimate models.

PMID- 8557188
TI  - Life, death, and the pursuit of apoptosis.

PMID- 8557189
TI  - Tubulogenesis in Drosophila: a requirement for the trachealess gene product.
AB  - The trachealess (trh) gene of Drosophila is required for embryonic tube
      formation. In trh mutants, tube-forming cells of the salivary gland, trachea, and
      filzkorper fail to invaginate to form tubes and remain on the embryo surface. We
      identified a P-element insertion that disrupts trh function and used the insert
      to clone and characterize trh. trh is expressed in the salivary duct, trachea,
      and filzkoper primordia, and expression persists in these cells throughout
      embryogenesis. trh expression in the salivary duct is controlled by the homeotic
      gene, Sex combs reduced (Scr), and by another salivary gland gene, fork head
      (fkh). trh is homologous to two transcription factors: the human hypoxia
      inducible factor-1 alpha and the Drosophila Single-minded protein.

PMID- 8557190
TI  - The Dictyostelium MAP kinase ERK2 regulates multiple, independent developmental
      pathways.
AB  - We showed previously that the MAP kinase ERK2 is essential for aggregation. erk2
      null cells lack cAMP stimulation of adenylyl cyclase and thus cannot relay the
      cAMP chemotactic signal, although the cells chemotax to cAMP (Segall et al.
      1995). In this paper we have examined the role of ERK2 in controlling
      developmental gene expression and morphogenesis during the multicellular stages,
      making use of a temperature-sensitive ERK2 mutation. Using suspension assays, we
      show that ERK2 is not essential for aggregation-stage, cAMP pulse-induced gene
      expression, or for the expression of postaggregative genes, which are induced at
      the onset of mound formation in response to cAMP in wild-type cells. In contrast,
      the prespore-specific gene SP60 is not induced and the prestalk-specific gene
      ecmA is induced but at a significantly reduced level. Chimeric organisms,
      comprised of wild-type and erk2 null cells expressing the prestalk-specific
      ecmA/lacZ reporter, show an abnormal spatial patterning, in which Erk2ts/erk2
      cells are excluded from the very anterior prestalk A region. To further examine
      the function of ERK2 during the multicellular stages, we bypassed the requirement
      of ERK2 for aggregation by creating an ERK2 temperature-sensitive mutant. erk2
      null cells expressing the ERK2ts mutant develop normally at 20 degrees C and
      express cell-type-specific genes but do not aggregate at temperatures above 25
      degrees C. Using temperature shift experiments, we showed that ERK2 is essential
      for proper morphogenesis and for the induction and maintenance of prespore but
      not prestalk gene expression. Our results indicate that ERK2 functions at
      independent stages during Dictyostelium development to control distinct
      developmental programs: during aggregation, ERK2 is required for the activation
      of adenylyl cyclase and during multicellular development, ERK2 is essential for
      morphogenesis and cell-type-specific gene expression. Analysis of these results
      and other supports the conclusion that the requirement of ERK2 for cell-type
      differentiation is independent of its role in the activation of adenylyl cyclase.

PMID- 8557191
TI  - DNA-binding determinants of the alpha subunit of RNA polymerase: novel DNA
      binding domain architecture.
AB  - The Escherichia coli RNA polymerase alpha-subunit binds through its carboxy
      terminal domain (alpha CTD) to a recognition element, the upstream (UP) element,
      in certain promoters. We used genetic and biochemical techniques to identify the
      residues in alpha CTD important for UP-element-dependent transcription and DNA
      binding. These residues occur in two regions of alpha CTD, close to but distinct
      from, residues important for interactions with certain transcription activators.
      We used NMR spectroscopy to determine the secondary structure of alpha CTD, alpha
      CTD contains a nonstandard helix followed by four alpha-helices. The two regions
      of alpha CTD important for DNA binding correspond to the first alpha-helix and
      the loop between the third and fourth alpha-helices. The alpha CTD DNA-binding
      domain architecture is unlike any DNA-binding architecture identified to date,
      and we propose that alpha CTD has a novel mode of interaction with DNA. Our
      results suggest models for alpha CTD-DNA and alpha CTD-DNA-activator interactions
      during transcription initiation.

PMID- 8557192
TI  - Oct-1 POU domain-DNA interactions: cooperative binding of isolated subdomains and
      effects of covalent linkage.
AB  - Structural and biochemical studies of Oct-1 POU domain-DNA interactions have
      raised important questions about cooperativity and the role of the linker
      connecting the POU-specific domain and the POU homeo domain. To analyze these
      interactions, we have studied binding of the isolated domains. Surprisingly, we
      find that two unlinked polypeptides corresponding to the POU-specific domain and
      the POU homeo domain bind cooperatively to the octamer site and have a coupling
      energy of 1.6 kcal/mole. We suggest that overlapping DNA contacts near the center
      of the octamer site may be the source of this cooperativity, as there are no
      protein-protein contacts between the domains in the crystal structure of the Oct
      1 POU domain-DNA complex. These studies also have allowed us to describe the
      thermodynamic contribution of the linker (present in the intact POU domain) in
      terms of an effective concentration (3.6 mM). The broader implications for
      understanding cooperativity in protein-DNA recognition and gene regulation are
      discussed.

PMID- 8557193
TI  - NF-kappa B-mediated chromatin reconfiguration and transcriptional activation of
      the HIV-1 enhancer in vitro.
AB  - NF-kappa B is a potent inducible transcription factor that regulates many genes
      in activated T cells. In this report we examined the ability of different
      subunits of NF-kappa B to enhance HIV-1 transcription in vitro with chromatin
      templates. We find that the p65 subunit of NF-kappa B is a strong transcriptional
      activator of nucleosome-assembled HIV-1 DNA, whereas p50 does not activate
      transcription, and that p65 activates transcription synergistically with Sp1 and
      distal HIV-1 enhancer-binding factors (LEF-1, Ets-1, and TFE-3). These effects
      were observed with chromatin, but not with nonchromatin templates. Furthermore,
      binding of either p50 or p65 with Sp1 induces rearrangement of the chromatin to a
      structure that resembles the one reported previously for integrated HIV-1
      proviral DNA in vivo. These results suggest that p50 and Sp1 contribute to the
      establishment of the nucleosomal arrangement of the uninduced provirus in resting
      T cells, and that p65 activates transcription by recruitment of the RNA
      polymerase II transcriptional machinery to the chromatin-repressed basal
      promoter.

PMID- 8557194
TI  - Drosophila TFIIA-S is up-regulated and required during Ras-mediated photoreceptor
      determination.
AB  - Photoreceptor induction in the developing Drosophila eye is triggered by the
      activation of the Ras pathway. Subsequently, the Ras-mediated activation of site
      specific transcription factors leads to the expression of putative "effector"
      genes. The coactivator function of the basal transcription factor TFIIA has been
      shown previously to enhance the trans-activation potential of site-specific
      transcription factors in vitro. Here, we show that the expression of the small
      subunit of TFIIA (dTFIIA-S) is specifically up-regulated in a transient manner
      during Ras-mediated photoreceptor induction. Furthermore, although null mutations
      in dTFIIA-S are cell lethal, a hypomorphic dTFIIA-S allele demonstrates an
      increased requirement for this factor during photoreceptor development. In
      addition, the cone cell to R7 photoreceptor transformation caused by ectopic
      activation of the Ras pathway during eye development is suppressed by the removal
      of one functional copy of the dTFIIA-S locus revealing the sensitivity of this
      process to reductions in dTFIIA-S activity. These results are the first in vivo
      evidence for the coactivator function in transcriptional enhancement proposed for
      TFIIA.

PMID- 8557195
TI  - The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for
      the organogenesis of the thyroid, lung, ventral forebrain, and pituitary.
AB  - The thyroid-specific enhancer-binding protein (T/ebp) gene was disrupted by
      homologous recombination in embryonic stem cells to generate mice lacking T/EBP
      expression. Heterozygous animals developed normally, whereas mice homozygous for
      the disrupted gene were born dead and lacked the lung parenchyma. Instead, they
      had a rudimentary bronchial tree associated with an abnormal epithelium in their
      pleural cavities. Furthermore, the homozygous mice had no thyroid gland but had a
      normal parathyroid. In addition, extensive defects were found in the brain of the
      homozygous mice, especially in the ventral region of the forebrain. The entire
      pituitary, including the anterior, intermediate, and posterior pituitary, was
      also missing. In situ hybridization showed that the T/ebp gene is expressed in
      the normal thyroid, lung bronchial epithelium, and specific areas of the
      forebrain during early embryogenesis. These results establish that the expression
      of T/EBP, a transcription factor known to control thyroid-specific gene
      transcription, is also essential for organogenesis of the thyroid, lung, ventral
      forebrain, and pituitary.

PMID- 8557196
TI  - Hlx homeo box gene is essential for an inductive tissue interaction that drives
      expansion of embryonic liver and gut.
AB  - The divergent murine homeo box gene Hlx is expressed in restricted hematopoietic
      cell types and, during embryogenesis, prominently in visceral mesenchyme of the
      developing liver, gall bladder, and gut. Targeted disruption of the gene has now
      established that it plays a key role in visceral organogenesis. Embryos
      homozygous for the mutation died around embryonic day 15 with anemia and severe
      hypoplasia of the liver and gut. Liver ontogeny commenced normally with formation
      of the liver diverticulum and differentiation of hepatocytes, but the organ
      failed to expand and reached only 3% of normal size. The apparent liver
      hypoplasia was not associated with a notable increase in apoptotic cells. Gut
      development also began normally, but the intestines failed to undergo extensive
      elongation and looping and reached only a quarter of normal length. The anemia
      resulted from a deficiency in the fetal form of hematopoiesis, which occurs in
      the liver, but no intrinsic defect in Hlx-/- hematopoietic cells was observed in
      vitro, and liver-derived Hlx-/- hematopoietic stem cells that were transplanted
      to irradiated normal mice could fully reconstitute hematopoiesis. The impaired
      fetal hematopoiesis therefore reflects insufficient support function provided by
      the minute liver. Hlx is normally expressed in visceral mesenchyme lying adjacent
      to the developing liver and gut epithelia affected by the mutation, but not in
      the epithelia themselves. Hence, Hlx regulates a mesenchymal-epithelial
      interaction that drives a vital growth phase in visceral organogenesis. Moreover,
      because mutation of Hlx blocked liver growth but not its specification, early
      morphogenesis, or differentiation, development of this organ appears to occur by
      step-wise inductive interactions under separate genetic control.

PMID- 8557197
TI  - Abnormal spermatogenesis in RXR beta mutant mice.
AB  - We have generated mouse lines in which the RXR beta gene was disrupted by
      homologous recombination. Approximately 50% of the RXR beta homozygous mutants
      died before or at birth, but those that survived appeared normal except that the
      males were sterile, owing to oligo-astheno-teratozoospermia. Failure of spermatid
      release occurred within the germinal epithelium, and the epididymis contained
      very few spermatozoa that, in addition, exhibited abnormal acrosomes and tails.
      There was a progressive accumulation of lipids within the mutant Sertoli cells,
      which were histochemically characterized as unsaturated triglycerides. In old
      mutant males, progressive degeneration of the germinal epithelium occurred,
      ending with the formation of acellular lipid-filled tubules. The selective
      expression of RXR beta in Sertoli cells, together with the timing of appearance
      of the histological abnormalities, suggests that the primary defect resulting
      from the mutation resides in these cells.

PMID- 8557199
TI  - "The Alzheimerization of aging": a response.

PMID- 8557198
TI  - trachealess encodes a bHLH-PAS protein that is an inducer of tracheal cell fates
      in Drosophila.
AB  - The embryonic tracheal system in Drosophila develops from placodes of precursor
      cells on the ectoderm. A transcription factor of the basic helix-loop-helix
      (bHLH)-PAS family, which is expressed in the nuclei of the tracheal cells
      throughout development, was identified. The protein shows the highest degree of
      homology to the Single-minded (Sim) protein. The transcript represents the
      previously identified trachealess (trh) locus, essential for tracheal
      development. Ectopic expression of trh leads to generation of extra tracheal pits
      and branches and to the expression of tracheal markers by patches of ectodermal
      cells. The expression of trh is consistent with a biphasic mode of
      transcriptional regulation. Expression is first induced by exogenous cues and is
      subsequently autoregulated. trh is also expressed and required in the posterior
      spiracles and the salivary gland ducts. The role of Trachealess in the formation
      of several tubular tissues in the embryo suggests that it may induce a general
      fate of branched tubular structures of epithelial origin.

PMID- 8557200
TI  - Changes in the living arrangements of older women: an international study.
AB  - This study analyzes trends in the percentage of older women living alone in 21
      European and North American countries over the period of 1960-1992. The general
      pattern is one of substantial annual increases in the percentage of elderly women
      living alone. This trend is shown to result mainly from demographic changes, with
      little evidence of a role for economic variables. The analysis suggests a
      reversal of the current trend in coming years, as mothers of postwar baby booms
      reach old age.

PMID- 8557201
TI  - Predicting nursing home admissions among incontinent older adults: a comparison
      of residential differences across six years.
AB  - Whether or not rates of nursing home admissions among elders with urinary
      incontinence varied by their place of residence was investigated. We also
      examined whether any observed residential differences could be accounted for by
      factors other than incontinence that are known to influence rates of
      institutionalization. Data from the Longitudinal Study on Aging (1984-1990) were
      used to examine a sample who at baseline lived in community settings and reported
      problems with urinary incontinence (n = 719). Analyses indicate that residents of
      less urbanized and thinly populated nonmetropolitan counties were more likely to
      have a nursing home admission than elders in any other residential context. More
      importantly, these residential differences persisted in multivariate logistic
      regression models after controls were introduced for sociodemographic
      characteristics, measures of health status, and indicators of the social support
      networks of the elders.

PMID- 8557202
TI  - The structure of informal care: are there differences by race?
AB  - This study investigated whether there are race differences in the structure of
      informal caregiving networks. Data on 3,793 functionally impaired persons age 65
      and over from the 1989 National Long-Term Care Survey were analyzed. The size of
      the total caregiver network and the unpaid network did not differ by race, but
      the likelihood of there being a non-immediate family member among unpaid
      caregivers was higher among disabled older blacks. These findings raise questions
      about whether race differences in nursing home utilization and paid long-term
      care services, documented in other studies, can be explained by differences in
      caregiving arrangements.

PMID- 8557203
TI  - Picture imperfect: hidden problems among Asian Pacific islander elderly.
AB  - Asian Pacific Islander (API) elderly represent the fastest growing group of
      ethnic elderly in the United States, yet their social and health needs remain
      little understood in the field of ethnogerontology. Existing literature generally
      portrays API elderly as in equal or better health compared to whites. However,
      aggregate API data cloud the bimodal distribution in socioeconomic and health
      status. We review existing literature on API elderly, and examine selected
      national data to illustrate the effects of a bimodal distribution on our
      understanding of API elderly socioeconomic and health status. Implications for
      research and policy are discussed.

PMID- 8557204
TI  - Elderly demographic profiles of U.S. states: impacts of "new elderly births,"
      migration, and immigration.
AB  - Many policy analysts take a narrow view toward assessing demographic change of
      state elderly populations by focusing only on the migration component. This
      article examines how 1990 state elderly populations have been affected by "new
      elderly births" (a state's population ages 55-59 in 1985 which survived to ages
      60-64 in 1990) as well as by migration components, over the 1985-90 period. It
      utilizes 1990 Census migration tabulations of the residence 5-years-ago question,
      along with demographic decomposition analysis. During this period, elderly births
      exerted a greater impact than migration on elderly gains and demographic
      compositions for all states. Migration from abroad is also important for state
      Latino and Asian elderly populations.

PMID- 8557205
TI  - Psychiatric and physical morbidity effects of dementia caregiving: prevalence,
      correlates, and causes.
AB  - The dementia caregiving literature is reviewed with the goals of (a) assessing
      the prevalence and magnitude of psychiatric and physical morbidity effects among
      caregivers, (b) identifying individual and contextual correlates of reported
      health effects and their underlying causes, and (c) examining the policy
      relevance of observed findings. Virtually all studies report elevated levels of
      depressive symptomatology among caregivers, and those using diagnostic interviews
      report high rates of clinical depression and anxiety. The evidence is more
      equivocal and generally weaker for the association between caregiving and
      physical morbidity, such as self-rated health, number of illnesses,
      symptomatology, health care utilization, preventive health behaviors, and
      cardiovascular functioning. Across studies, psychiatric morbidity in caregivers
      was linked to patient problem behaviors, income, self-rated health, perceived
      stress, and life satisfaction. Physical morbidity was associated with patient
      problem behaviors and cognitive impairment, and with caregiver depression,
      anxiety, and perceived social support. Possible causes of reported effects and
      policy implications are discussed.

PMID- 8557206
TI  - A comprehensive support program: effect on depression in spouse-caregivers of AD
      patients.
AB  - Caregivers of Alzheimer's disease patients often suffer from depression. Using a
      longitudinal treatment/control study, we examined the effects of a comprehensive
      support program on depression in spouse-caregivers. This psychosocial
      intervention program treats the primary caregiver and family members over the
      entire course of the disease through individual and family counseling, the
      continuous availability of ad hoc counseling, and support group participation. In
      the first year after intake, the control group became increasingly more
      depressed, whereas the treatment group remained stable. By the eighth month,
      treated caregivers were significantly less depressed than those in the control
      group. These results suggest that enhancing long-term social support can have a
      significant impact on depression in caregivers.

PMID- 8557207
TI  - How costly is it to care for disabled elders in a community setting?
AB  - This article describes the total cost of care, including both informal caregiving
      and formal services for a cohort of disabled elderly living in the community. The
      cost of informal caregiving hours was calculated using a market value approach.
      The total annual cost of caring was estimated to be $9,600. Increased disability
      was associated with increased costs. High-cost elders were more likely to be
      severely disabled, live with their caregiver, and become institutionalized. For
      most elders, even the cost of a complete substitution of informal care for formal
      services, plus living expenses, was less costly than nursing home care.

PMID- 8557208
TI  - An instrument to assess the oral health status of nursing home residents.
AB  - This article presents data from the development and testing of an instrument to
      evaluate the oral health of nursing home residents by nursing personnel (RNs,
      LVNs, and CNAs). After the instrument was developed, nursing staff were taught to
      do a brief oral health status examination (BOHSE). Using the instrument, a
      dentist examined 100 residents; the examination was repeated on the same
      residents by each category of nurse examiners. Correlation coefficients indicate
      that statistically significant interrater reliability between the three
      categories of nursing personnel and the dentist was established, suggesting that
      nursing staff can be taught to evaluate the oral health of residents. Replication
      of the study in multiple sites is recommended.

PMID- 8557209
TI  - Family policies for an aging society: moving to the twenty-first century.
AB  - Most family policy implicitly or explicitly focuses on families with young
      children, but the revolution in longevity suggests the value of a life course
      focus, aimed at promoting the effectiveness of families and individuals at all
      ages and stages. Gerontologists can make a contribution by documenting and
      describing the gaps between needs and resources of families at all life stages,
      developing family indicators of social change, and sensitizing both decision
      makers and the public to the unintended consequences of existing or proposed
      policies.

PMID- 8557210
TI  - A moving experience: reconfiguring a special care unit for Alzheimer's patients.
AB  - Eight years after opening, the patient mix on a 64-bed Special Care Unit (SCU)
      for Alzheimer's residents had become too diverse to allow the intended
      programming to be carried out. The unit was carefully reconfigured with residents
      moving within, to, and from the unit. Successful moves typically involve
      residents in pre-move planning and preparation activities, but since this isn't
      feasible with dementia patients, extensive planning, training, and preparation of
      staff substituted for the involvement of residents. The move met its objectives:
      resident mix and programming are back to the original intent, and quality of life
      has improved. Improved discharge policies maintain homogeneity of resident levels
      on the unit. The change produced unexpected changes, and staff, particularly the
      Certified Nursing Assistants (CNAs), had to make immediate adjustments. Greater
      CNA involvement is recommended.

PMID- 8557211
TI  - An interdisciplinary mental health consultation team in a nursing home.
AB  - The Mental Health Consultation Team (MHCT) at the Portland Veterans Affairs
      Medical Center nursing home is an interdisciplinary group of mental health
      professionals and primary care providers established to triage mental health
      consultations, improve communication between consultants and primary care
      providers, help staff translate consultants' recommendations into patient care,
      and furnish education in the management of mental health problems. The MHCT has
      decreased the demands for formal psychiatry and psychology consultations while
      increasing mental health services through innovative use of existing staff.

PMID- 8557212
TI  - Epidemiology and pathoetiology of neurological syndromes with hyperthermia.

PMID- 8557213
TI  - Antidegenerative effects of Mg(2+)-valproate in cultured cerebellar neurons.
AB  - We have investigated in the present study the effect of Mg(2+)-valproate on
      necrotic degeneration induced by an excitotoxic insult in primary culture of
      cerebellar neurons, that is an homogeneous population of glutamatergic neurons.
      Mg(2+)-valproate protected cultures against glutamate-induced neurotoxicity,
      acting as an indirect N-methyl-D-aspartate (NMDA) receptor antagonist, thus
      reducing free radical formation and affecting the biochemical parameters (i.e.
      45Ca(2+)-influx, cyclic GMP formation, inositol phospholipid hydrolysis and
      protein kinase C translocation) that undergo modifications following NMDA
      receptor activation in cerebellar granule cells.

PMID- 8557214
TI  - Sympathetic skin response in patients with amyotrophic lateral sclerosis.
AB  - To determine a possible involvement of the autonomic nervous system in
      amyotrophic lateral sclerosis (ALS), measurement of the sympathetic skin response
      (SSR) was performed in 15 patients with definite ALS. Findings were compared with
      those in 20 normal controls. In ALS patients the mean SSR latencies recorded from
      the palms and soles were both significantly prolonged (p < 0.05) and the
      amplitudes were reduced as compared with normal persons. In 5 patients, SSR
      potentials were completely lacking in one or even more extremities. Our data
      strongly suggest subclinical involvement of the autonomic nervous system in ALS
      as assessed by the SSR response. In our patients the extent of autonomic
      dysfunction was not related to the stage or the duration of disease.

PMID- 8557215
TI  - Distribution of muscle fibre types in human skeletal muscle fascicles: an autopsy
      study of three human muscles.
AB  - The predominance of type 2 fibres in the periphery of the muscle fascicle is a
      phenomenon attributed to local factors or to the adaptation of the muscle to
      functional needs. As the majority of relevant studies has been performed on
      quadriceps muscle of males, the purpose of this study was to examine other
      muscles along with quadriceps, in females as well as in males, with parallel
      morphometric analysis of fibres, in order to determine whether differences in
      size exist in addition to differences in proportion. Cryostat sections (ATPase,
      pH 9.4) were studied from 13 quadriceps femoris, 13 biceps brachii and 11 deltoid
      muscles taken at autopsy from 11 males and 8 females. The number and smallest
      diameter of type 1 and 2 fibres were counted and the percentage and mean diameter
      of the two types of fibres were calculated in the interior and the periphery of
      randomly selected fascicles. We found that: the predominance of type 2 fibres in
      the periphery is constant in all muscles studied, regardless of sex and age;
      there is a progressive age-related reduction in the diameter of type 2 fibres.

PMID- 8557216
TI  - Terguride in stable Parkinson's disease.
AB  - Terguride (TER) (2 mg/day) was compared with a placebo in 41 stable Parkinson's
      disease (PD) patients, so as to test its efficacy as an add-on treatment to spare
      levodopa (LD). After the 4th week of add-on treatment, LD was reduced by about
      25%. The number of "stable" patients (--those with an increase of no more than
      20% of the basal Columbia University Rating Scale (CURS) score--remaining after
      LD reduction was used to compare the two add-on treatments. Most patients,
      remained "stable" in spite of LD reduction, and no significant differences
      between the therapies were discovered; the CURS score decreased over time only in
      the TER group. Hence, TER was shown to be a drug that has DA-ergic properties but
      with minimal antiparkinsonian efficacy.

PMID- 8557217
TI  - Anatomical evidence of somatosensory neuroplasticity during foetal life?

PMID- 8557219
TI  - Infertility and breast cancer risk.

PMID- 8557218
TI  - Systemic administration of pramiracetam increases nitric oxide synthase activity
      in the cerebral cortex of the rat.
AB  - The effect of systemic administration of pramiracetam on neuronal type nitric
      oxide synthase (NOS) activity and NOS mRNA expression were studied in the
      hippocampus and cerebral cortex in rats. A dose of 300 mg/kg (i.p.) of this
      nootropic produced an approximately 20% increase in NOS activity in rat brain
      cortical homogenates but not in hippocampal homogenates; no significant changes
      were observed in NOS mRNA expression in the cortex and hippocampus. A lower dose
      of pramiracetam (100 mg/kg i.p.) was ineffective on NOS mRNA expression and
      enzyme activity. Interestingly, administration of pramiracetam (300 mg/kg i.p.)
      in rats pretreated (24 h before) with lithium chloride (LiCl) (3 mEq/kg i.p.)
      yielded a 40% increase in cortical NOS activity. However, in LiCl-pretreated rats
      this nootropic failed to affect cortical NOS mRNA expression; LiCl (3 mEq/kg
      i.p.) given alone produced no effect. In conclusion, the present data demonstrate
      that pramiracetam given alone or in combination with LiCl increases NOS activity
      in brain cortical homogenates of rats and this may contribute to the mechanisms
      underlying learning and memory improvement produced by this nootropic.

PMID- 8557220
TI  - Primary invasive vaginal carcinoma treated with radiotherapy: analysis of
      prognostic factors.
AB  - Between 1965 and 1988, 125 patients with primary invasive vaginal carcinoma were
      treated with radiation therapy at the Center of Oncology in Krakow. Twenty-two
      superficial stage I patients received radium or cesium intracavitary radiation
      alone. The remaining 11 patients with stage I disease whose lesions were either
      large or thick and 77 patients with stages II and III were treated with a
      combination of external irradiation followed by intracavitary brachytherapy.
      Fifteen patients with stage IVA received external irradiation only. Five-year NED
      survival was achieved in 42.4% of patients. In the Cox multivariate analysis
      three variable were independently related to beneficial survival: grade G1 + G2,
      stage I + II, and age below 60 years. Of 66 patients who died of vaginal cancer,
      locoregional failure was found in 51 (77.3%), locoregional and distant in 5
      (7.6%), and distant only in 10 (15.1%) patients. Late radiation morbidity
      occurred in 16 (12.8%) patients.

PMID- 8557221
TI  - Endometrial carcinoma associated with hyperplasia.
AB  - The aim of this study was to clarify the relationship of endometrial hyperplasia
      to endometrial carcinoma. From 1979 through 1990, 115 cases of stage I-IV
      endometrial carcinomas treated initially by hysterectomy were reviewed
      histologically. Forty-two of 115 (36.3%) patients had hyperplasia in the
      endometrium adjacent to the carcinoma. Women with both endometrial carcinoma and
      hyperplasia were significantly younger than those with carcinoma without
      hyperplasia (P < 0.05). In a comparison of patients with carcinoma without
      hyperplasia, those with hyperplasia were better differentiated (P = 0.0072), and
      lacked deep myometrial invasion (P < 0.0001), cervical involvement (P = 0.0192),
      lymph-vascular space invasion (P = 0.0102), and para-aortic lymph node metastases
      (P = 0.0434). The presence of endometrial metaplasia (P = 0.0001). The estimated
      5-year survival rates for patients with carcinoma with hyperplasia and those with
      carcinoma without hyperplasia were 96.55 and 73.33%, respectively (P = 0.0016).
      In endometrial carcinomas, the presence of endometrial hyperplasia may
      demonstrate a more favorable prognosis.

PMID- 8557222
TI  - Transvaginal color Doppler ultrasound in the assessment of invasive cervical
      carcinoma.
AB  - OBJECTIVE: To assess the validity of transvaginal color Doppler flow in the
      prediction of malignancy in the uterine cervix. STUDY DESIGN: Sixteen women with
      cervical pathology (14 with invasive carcinoma and 2 with cervical
      intraepithelial neoplasia III) were examined using transvaginal sonography as
      well as transvaginal color Doppler with measurements of the resistance index of
      tumor blood flow. Twenty-four women with histologically proven normal cervices
      served as a control group. RESULTS: Resistance index (RI) was significantly lower
      in the study group [0.493; 0.475-0.511 (mean + 95% CI)] than in control group
      [0.643; 0.627-0.659] (P < 0.0001) (t'). There was no statistically significant
      difference between the carcinoma group and the CIN III cases (P = 0.067) (t').
      Only two cases with cervical carcinoma showed dense vascularity with color
      Doppler. A RI cutoff less than or equal to 0.573 showed a sensitivity of 81% with
      a specificity of 93%, a positive predictive value of 93%, and a negative
      predictive value of 81%. CONCLUSION: Color Doppler flow evaluation of RI in
      cervix vessels may aid in the early diagnosis and management of cervical
      carcinoma and in differentiating benign from malignant tumors. The validity of
      this technique as a screening program for diagnosis is limited.

PMID- 8557223
TI  - Risk of breast cancer in a cohort of infertile women.
AB  - The purpose of this study was to assess: (1) the risk of breast cancer associated
      with use of ovulation-inducing agents (such as clomiphene citrate) as treatment
      for infertility; and (2) the risk associated with ovulatory abnormalities that
      result in infertility. We performed a case-cohort study among 3837 women
      evaluated for infertility at clinics in Seattle, Washington, at some time during
      1974-1985. Computer linkage with a population-based tumor registry was used to
      identify women diagnosed with breast cancer before January 1, 1992. Data
      regarding infertility testing and treatment were abstracted from the infertility
      clinic medical records for women who developed breast cancer and a randomly
      selected subcohort. Twenty-seven women in the cohort developed in situ or
      invasive breast cancer, in comparison with an expected number of 28.8 cases
      (standardized incidence ratio, 0.9; 95% confidence interval (CI), ).6-1.4).
      Infertile women with evidence of an ovulatory abnormality were at a risk of
      breast cancer similar to that of women whose infertility was believed to be due
      to other causes. The risk among women who had taken clomiphene was reduced
      relative to infertile women who had not used this drug (adjusted relative risk,
      0.5; 95% CI, 0.2-1.2), but the reduction in risk did not increase with duration
      of use. The possibility that use of clomiphene as treatment for infertility
      lowers the risk of breast cancer should be examined in other, larger studies.

PMID- 8557224
TI  - Human papillomavirus is associated with the frequent detection of warty and
      basaloid high-grade neoplasia of the vulva and cervical neoplasia among
      immunocompromised women.
AB  - A total of 158 women who either HIV-infected or under iatrogenic
      immunosuppression were examined regularly during a 4-year period to evaluate if
      certain vulvar neoplasms and cervical neoplasia have similar associated risk
      factors. Patients with CIN were matched prospectively with immunocompetent
      controls with CIN. Forty-eight cervical lesions were detected among patients,
      including 2 invasive carcinoma and 15 CIN-3 lesions, compared to 11 vulvar
      lesions, including 2 invasive carcinoma and 7 VIN-3 lesions. Women who have more
      than five life-time partners were more likely to have HPV-DNA positive cervical
      swabs and vulvar scrapes as well as cervical and/or vulvar neoplasia. Compared to
      2.7% of controls 15.2% of patients with CIN had coexisting high-grade lesions of
      the vulva. With 1 exception all patients with vulvar neoplasia either suffered
      from symptomatic immunodeficiency or received immunosuppressive drugs for more
      than 10 years. Except for 1 VIN-3 lesions, all vulvar neoplasms were associated
      with HPV-DNA types 16, 31, and/or 33. Six of nine patients as well as the 2
      controls with coexisting vulvar and cervical neoplasia had the same HPV-type
      associated with both lesions. All vulvar lesions were classified as either
      "warty" or "basaloid". In conclusion cervical and bowenoid/basaloid vulvar
      neoplasia seem to have a similar HPV-related genesis. Malfunction of the cellular
      immune response appears to be a cofactor in the genesis of HPV-associated
      neoplasia at both sites.

PMID- 8557225
TI  - Aberrations in normal systemic lipid metabolism in ovarian cancer patients.
AB  - Numerous investigations have demonstrated altered systemic lipid metabolism in
      cancer patients, as well as aberrant lipid utilization by tumor cells. The most
      common measure of altered systemic lipid metabolism in these individuals has been
      hyperlipidemia. Although cachexia is not generally considered to be associated
      with gynecologic cancers, this study demonstrates the presence of lipolysis
      promoting activity, detectable in sera and ascites of ovarian cancer patients and
      indices of altered systemic lipid metabolism. Elevated lipolysis promoting
      activity was detectable in the sera of 7/9 patients and in the ascites of 5/5
      patients. Since previous studies have indicated that cancer patients exhibit a
      2.5-fold enhancement in hormone-sensitive lipase (HSL) versus normal controls, as
      a potential mechanism for elevated lipolysis, the ability of ascites-derived
      factors to induce HSl was examined. The addition of three of four ascites fluids
      increased the level of HSL in normal adipocytes. All of the patients' samples
      exhibited elevated lipid levels versus normal peritoneal fluid. Isolation and
      analysis of lipids from three ovarian cancer patients revealed four consistent
      altered lipid parameters compared to normal peritoneal fluid: elevated
      monoglycerides, diglycerides, and free fatty acids and decreased
      triacylglycerides. While "classical" cachexia is not a common feature of ovarian
      cancer, the presence of circulating lipolysis-promoting activity and altered
      lipid metabolism, generally observed in cachectic individuals, can be
      demonstrated in these ovarian cancer patients. Based on recent evidence
      indicating a role of lipids in carcinogenic initiation or promotion, the presence
      of tumor-derived lipolysis-promoting factor and lipid metabolism alterations may
      provide a mechanism for the epidemiologically observed association between lipids
      and certain cancers, including ovarian cancer.

PMID- 8557226
TI  - Effect of total treatment of time on event-free survival in carcinoma of the
      cervix.
AB  - The objective of this study was to analyze the effect of radiation therapy
      duration on event-free survival in patients with invasive carcinoma. Three
      hundred and sixty patients with FIGO stage IB-IIIB carcinoma of the cervix were
      treated with external radiation and brachytherapy as first line therapy. Median
      therapy duration was 45 days. Patients were classified according to whether they
      had rather long therapies, taking 60 days (the 75th percentile) as an arbitrary
      cutoff. Cumulative incidences of local recurrence, metastasis, and death were
      estimated. The 5-year event-free survival rate was 59 +/- 3% for the less than 60
      days group and 42 +/- 7% for the more than 60 days group (P = 0.003). In terms of
      univariate hazard ratio (HR), the relative difference between the two groups
      corresponds to an increase in hazard of any of the three events considered more
      than the double (HR = 1.756, P = 0.003) for the longer therapy duration group. A
      multivariate analysis, which included selected prognostic factors, confirmed
      these results (HR = 1.76, P = 0.017). A short radiation therapy duration is a
      highly significant prognostic factor associated with longer event-free survival
      in carcinoma of the cervix.

PMID- 8557227
TI  - A comparison of end and loop colostomy for fecal diversion in gynecologic
      patients with colonic fistulas.
AB  - OBJECTIVE: The purpose of this study was to evaluate the early morbidity, stomal
      complications, and overall survival rate of gynecologic oncology patients treated
      with end or loop colostomy for management of colonic fistula. METHODS: Seventy
      five women with fistulas undergoing fecal diversion procedures from 1983 to 1993
      were identified. Information relevant to tumor history, type of fistula,
      operative procedure, complications, and outcome was extracted from the medical
      records. RESULTS: A recto- or sigmoid-vaginal fistula was present in 55 patients.
      The remaining 20 patients had either a colonic fistula involving the bladder,
      uterus, or skin or multiple fistulas. In 66 (88%) patients, the pelvis had been
      irradiated. Loop colostomy was performed in 47 (63%) patients and end colostomy
      in 28 (37%) of patients. Cancer was present in 31 (66%) of 47 patients undergoing
      loop colostomy compared with 12 (43%) of 28 patients undergoing end colostomy (P
      = 0.05). No significant differences were detected with regard to age at cancer
      diagnosis or age at the time of colostomy, body habitus, medical condition, type
      of cancer, history of pelvic irradiation, or incidence of multiple or complex
      fistulas. Median operative time was increased by 1 hr and median blood loss from
      50 to 200 ml with end colostomy. No significant advantage of loop colostomy over
      end colostomy was detected in the incidence of acute morbidity or hospital stay.
      Early stomal complications occurred in 8 patients, 7 of whom had loop colostomy
      (P = 0.25). Delayed complications (prolapse, retraction, stool per vagina, or
      fistula) following loop colostomies occurred more frequently than following end
      colostomy: 12 (26%) of 47 compared with 2 (7%) of 28 (P = 0.05), respectively.
      Five loop stomas were later converted to end stomas. In addition only one of four
      attempted loop colostomy closures was successful. Overall survival in both groups
      of patients was similar. CONCLUSION: There were no statistically significant
      differences between patients treated with loop or end colostomy with regard to
      early morbidity or survival. The early and frequent occurrences of stomal
      complications after loop colostomy overshadow the clinically minor advantages of
      this method of fecal diversion. Although loop colostomy was performed more often
      in this setting, these data do not support its routine use for the management of
      gynecologic oncology patients with fistulas.

PMID- 8557228
TI  - Ovarian tumors in postmenopausal breast cancer patients treated with tamoxifen.
AB  - From September 1, 1989, to November 30, 1994, 175 menopausal breast cancer
      patients treated with tamoxifen were followed at the authors' institutions.
      During this period. 16 (9.1%) underwent total abdominal hysterectomy and
      bilateral salpingo-oophorectomy, for various indications. Of these, 10 (62.5%)
      had either uni- or bilateral ovarian tumors. The analysis of surgical findings
      showed an incidence of 5.7% (10/175) ovarian tumors among all the patients. In 2
      (20%), the ovarian masses displayed enlargement over a relatively short period
      while on treatment. In 5 (50%) patients, the findings were bilateral. All tumors
      were detectable by ultrasonography, except four serous cystadenomas found in 3
      women. The mean duration of tamoxifen treatment was 36.6 +/- 24.9 (range 9-86)
      months. The rate of 5.7% for ovarian tumors, in this selected group of patients,
      is four to five times higher than that reported for similar pathologic conditions
      detected by general screening with ultrasonographic scans among nonselected,
      asymptomatic, and untreated postmenopausal women. Two possibilities should be
      considered in the development of ovarian tumors coinciding with tamoxifen
      treatment; (1) women with breast malignancy are prone to develop benign or
      malignant ovarian tumors in relation to genetic factors, regardless of tamoxifen
      treatment; and (2) tamoxifen may stimulate enlargement of such tumors and may
      even cause them.

PMID- 8557229
TI  - Treatment of advanced or recurrent endometrial carcinoma with combination of
      etoposide, cisplatin, and 5-fluorouracil: a phase II study.
AB  - Forty-nine consecutive patients with metastatic or recurrent endometrial
      carcinoma were treated with a monthly combination chemotherapy consisting of VP
      16-213 80 mg/m2 i.v. Days 1-3, 5-fluorouracil (5-FU) 600 mg/m2 i.v. Days 1-3, and
      cisplatin 35 mg/m2 i.v. Days 1-3. The objective response rate was 41% (95% CI, 27
      54%) with 14.3% complete responses. The median survival duration was 14 months.
      The median response duration was 12 months. The estimated median survival for
      responders was 20 months. Three patients are still free of disease 5 years after
      treatment. The major toxic effects were myelosuppression (less than 25% of grade
      III and IV leucopenia, and 14% grade III and IV thrombocytopenia). Grade III
      peripheral neuropathy was observed in five patients. Cisplatin administration had
      to be stopped due to renal toxicity in six patients. No treatment-related deaths
      occurred. The combination of etoposide, 5 fluorouracil, and cisplatin is an
      effective regimen with an acceptable toxicity in patients with recurrent or
      metastatic endometrial carcinoma.

PMID- 8557230
TI  - Bolus mitomycin C and 5-FU with sequential radiation for poor-prognosis locally
      advanced cervical cancer.
AB  - Forty patients with locally advanced cervical carcinoma were entered into a
      protocol utilizing the bolus administration of both mitomycin C (10 or 15 mg) on
      Day 1 and 5-fluorouracil (400 mg) on Day 1-5 followed by sequential pelvic
      irradiation on Day 6 between September 1980 and October 1985. All patients had
      poor-prognosis FIGO stage IB, IIB, IIIB, or IVA disease. Only patients with poor
      prognosis factors such as bulky tumor masses of 5 cm or greater noted on the
      initial physical exam (37 patients) or poorly differentiated histology (3
      patients) were eligible for this study. There were three severe side effects seen
      in the 24 patients receiving 15 mg mitomycin C. One patient developed
      thrombocytopenia, one patient developed acute radiation enteritis, and the third
      patient developed radiation proctitis requiring laser therapy. Only 1 of 16
      patients receiving 10 mg mitomycin C developed a complication (thrombocytopenia).
      Neutropenia was mild in all patients. No infections were seen. Thrombocytopenia
      never warranted platelet transfusion. No patients developed therapy-related bowel
      obstruction or fistulae. Median follow-up was 11.3 years with a range of 6.2-14.2
      years. A complete response rate of 63%, a local control rate of 58%, and a 5-year
      survival rate of 44% were obtained. This does not appear to offer any benefit
      over radiation alone. This present study supports the superiority of higher dose
      concurrent infusional chemotherapy and radiation over low-dose sequential bolus
      chemotherapy and radiation.

PMID- 8557231
TI  - p53 gene mutation analysis and antisense-mediated growth inhibition of human
      ovarian carcinoma cell lines.
AB  - Targeting dysfunctional gene expression in the cancer cell with gene-specific
      therapeutics requires knowledge of the structure and expression of the designated
      gene. Because of the prevalence of p53 dysfunction in epithelial ovarian
      carcinoma, modulation of the expression of this tumor suppressor gene is an
      attractive target for gene therapy. We sequenced the p53 gene and analyzed its
      expression in 10 ovarian cancer cell lines. Only five cell line mutations were
      encountered, three associated with a loss of heterozygosity. Thus, neither p53
      mutation nor allelic loss is required for ovarian carcinogenesis or propagation
      of ovarian cancer cell lines in vitro. SSCP screening, but not
      immunohistochemical staining, correlated with results of direct genomic
      sequencing. All p53 immunohistochemical-negative cell lines differed from that
      reported by another laboratory, underscoring the importance of the knowledge of
      target gene expression in a given cell line in a given laboratory. We designed
      pilot studies of antisense oligodeoxynucleotides directed against the p53 gene
      based on our sequence data. Differential growth inhibition of the A2780-CP-20
      cell line (mutant p53 protein), but not of the OVCAR-3 cell line (wild-type p53
      protein) confirmed the potential usefulness of this strategy.

PMID- 8557232
TI  - OncoLink: a cancer information resource for gynecologic oncologists and the
      public on the Internet.
AB  - The Internet is a computer network accessible to over 30 million computers users
      worldwide. By default, it has become the "information superhighway" that is
      growing at an explosive rate of between 1 and 2 million new users per month.
      Internet contains thousands of information of interest to cancer patients and
      healthcare professionals. Identifying the outstanding "golden" resources from the
      chaos is difficult. To address this problem and to provide information specific
      to gynecologic oncology, we developed a cancer information server called
      "OncoLink" at our institution that is available at no cost 24 hr per day, 7 days
      per week to all Internet users. OncoLink has two major goals: (1) To provide
      quality, original content for cancer patients and healthcare professionals and
      (2) to provide well-organized, consistent access to existing Internet cancer
      resources. This service may be used by anyone with a Microsoft Windows, Apple
      Macintosh, or UNIX computer. The service is rich in multimedia content containing
      text, pictures, illustrations, sound, and video. The information includes (1)
      original content written by authors at our institution, (2) original content
      submitted by authors from other institutions and, (3) publicly available
      information from other resources. Patient-oriented articles, physician-oriented
      review articles, and NIH, NCI, and FDA documents are available. All content is
      reviewed by an Editorial Board prior to posting. We have kept a detailed log file
      of each time the system has been accessed by an Internet user. OncoLink went
      online in March 1994. During the first 18 months (542 days) of operation, the
      service received 4,051,901 request for information from 105,589 unique Internet
      addresses worldwide. There is tremendous public and professional demand for
      online cancer information via the Internet. We feel that the Internet is an
      outstanding vehicle for providing quality cancer information for gynecologic
      oncologist other healthcare professionals, and the public.

PMID- 8557233
TI  - The expression of epidermal growth factor receptor, HER-2/Neu, p53, and Ki-67
      antigen in uterine malignant mixed mesodermal tumors and adenosarcoma.
AB  - Uterine malignant mixed mesodermal tumors (MMMT) are highly malignant tumors
      containing both malignant glands and stroma, while adenosarcomas (AS) are less
      aggressive tumors composed of malignant stroma and benign glands.
      Immunohistochemistry was used to grade overexpression of p53 protein, HER-2/neu
      protein, epidermal growth factor receptor (EGFR), and Ki-67 antigen in both the
      glands and stroma of tissue from 20 women with MMMT and 6 women with AS. EGFR was
      overexpressed in 2 AS and 9 MMMT, and was more commonly found in the sarcomatous
      component than the carcinomatous component in MMMT (P = 0.03). p53 was not found
      in any AS samples and was strongly present in 6 MMMT samples with a random
      distribution between the malignant components. HER-2/neu protein was not
      overexpressed in any AS or primary MMMT. Ki-67 antigen, a marker of cell
      proliferation, was found at higher levels in MMMT than AS samples (P = 0.03) and
      high Ki-67 antigen expression correlated with a decreased survival in patients
      with MMMT (P = 0.004). Independent characterization of oncogene proteins in the
      malignant components of these heterogeneous tumors may provide insight into the
      histogenesis and behavior of these malignancies.

PMID- 8557234
TI  - Recurrent placental site trophoblastic tumor of the uterus: clinical, pathologic,
      ultrastructural, and DNA fingerprint study.
AB  - Placental site trophoblastic tumor is a rare disease. Most benign cases of this
      disease show a few mitotic figures of the tumor while recurrent cases usually
      have more than 5 mitoses per 10 high-power fields. The present case was primarily
      treated by hysterectomy and chemotherapy and had 2 mitoses in 10 high-power
      fields. After 1 years and 4 months of therapy the patients was diagnosed as
      ovarian metastasis because of gradually increasing serum beta-human chorionic
      gonadotropin (hCG) level and abnormally high fluid levels of beta-hCG and human
      placental lactogen (hPL) punctured from her cystic ovarian tumor. This recurrent
      case was further treated with another regimen of chemotherapy for 7 courses, and
      the serum beta-hCG level had decreased at present. This report describes the
      recurrent case and discusses the histology of a few mitotic figures, electron
      microscopic findings, and results of the DNA fingerprint analysis of the primary
      tumor.

PMID- 8557235
TI  - Paclitaxel-induced "recall" soft tissue ulcerations occurring at the site of
      previous subcutaneous administration of paclitaxel in low doses.
AB  - The presented case reports a rare complication of paclitaxel misuse: recall soft
      tissue injury at the site of previous subcutaneous paclitaxel administration.
      Generally, paclitaxel extravasation causes only mild dermatologic toxicity and
      ulcerations are rare. We describe the third case of a so-called recall dermatitis
      following paclitaxel chemotherapy. In contrast to the previously reported cases,
      soft tissue damage arose at the abdominal wall at the injection sites of
      previously administered subcutaneous paclitaxel in homeopathic doses of 1.0 mg.
      The recall reaction continued to exacerbate after each course of systemic
      paclitaxel chemotherapy and finally led to surgical treatment. The course of the
      observed skin toxicity makes it probable that the pathomechanisms involved in
      these recall reactions are different from these responsible for the limited skin
      toxicity observed after paclitaxel extravasation.

PMID- 8557236
TI  - Comparative aspects of regulation and function of the adrenal complex in
      different groups of vertebrates.

PMID- 8557237
TI  - Effect of timely insulin administration on pancreatic B-cells of Otsuka-Long
      Evans-Tokushima-Fatty (OLETF) strain rats. An animal model of non-insulin
      dependent diabetes mellitus (NIDDM).
AB  - Morphological changes of the pancreas and impairment of pancreatic B-cell
      function in a model rat (Otsuka Long Evans Tokushima Fatty [OLETF]) with non
      insulin dependent diabetes mellitus might be the result of over-activity of B
      cells to compensate for insulin insensitivity. To test this possibility, we
      studied whether the histological and functional alterations in the pancreas of
      male OLETF rats were improved by treatment with insulin for a certain period,
      which might reduce the burden to B-cells. Groups of 6 male OLETF rats and 5 or 4
      male non-diabetic control Long Evans Tokushima Otsuka (LETO) rats received
      injections of insulin (Ultralente MC; 10 U/kg/day to OLETF rats, 5 U/kg/day to
      LETO rats) or saline subcutaneously, once a day for 3 weeks from 24 weeks of age.
      Then their insulin responses to glucose (200 mg/dl) and arginine (10 mmol/l) were
      examined by perfusion of the pancreas. The morphological features of their
      pancreata were also examined. The insulin response to glucose in OLETF rats
      treated with insulin was significantly higher than that of OLETF rats treated
      with saline (sigma IRI 142.5 +/- 27.0 vs. 37.4 +/- 6.3 ng/ml.20 min, p < 0.05)
      and unlike in the latter showed the normal two phases. The morphological changes
      of the pancreas in the insulin-treated OLETF rats were remarkably ameliorated,
      animals showing no enlargement and only slight fibrosis of islets. Thus treatment
      with insulin was effective for preventing B-cell dysfunction and morphological
      changes of the pancreas in NIDDM model rats.

PMID- 8557238
TI  - 1,25 dihydroxyvitamin D and dexamethasone decrease in vivo Walker carcinoma
      growth, but not parathyroid hormone related protein secretion.
AB  - Parathyroid hormone related protein (PTHrP) is produced by several breast
      cancers. 1,25 dihydroxyvitamin D (1,25[OH]2D) and Dexamethasone (DEX) have been
      shown to decrease PTHrP mRNA expression in several cell lines. We therefore
      tested the in vivo effect of both steroids on PTHrP secretion and tumor
      development of the Walker carcinoma (WC). WC cells were injected subcutaneously
      in Fisher rats which were simultaneously treated with either vehicle, or
      1,25(OH)2D (0.5 micrograms/kg/d) or DEX (2 mg/kg/d). After 7 days, tumor weight
      was significantly decreased in the 2 treated-groups as compared to the control
      group. Vehicle treated-rats developed hypercalcemia, which was also observed in
      rats treated with 1,25(OH)2D; by contrast, the plasma calcium was significantly
      decreased in the DEX-treated group compared to vehicle-treated rats. In a dose
      effect experiment, this dose of 1,25(OH)2D induced marked hypercalcemia in rats
      not implanted with WC, but was required to decrease the tumor weight in implanted
      rats. In both 1,25(OH)2D and DEX-treated groups, plasma PTHrP levels were
      significantly decreased, but there was a similar correlation between PTHrP plasma
      level and tumor weight in the three groups. Indeed, the cytosolic PTHrP
      content/mg tumor was identical in the 3 groups. By contrast, the PTHrP/Actin mRNA
      in the tumor was significantly decreased in the 1,25(OH)2D group, comparatively
      to the vehicle and DEX groups. Our results show that Dexamethasone and 1,25(OH)2D
      decrease WC tumor development in vivo, but do not change the PTHrP secretion by
      the remaining tumor although steady state PTHrP mRNA content level is decreased
      by 1,25(OH)2D.

PMID- 8557239
TI  - Adenosine A1-receptors inhibit cAMP and Ca2+ mediated calcitonin secretion in C
      cells.
AB  - The effect of the adenosine A1 receptor activation on calcitonin secretion was
      studied in medullary thyroid carcinoma cells of the rat (rMTC 6-23). Calcitonin
      was determined by radioimmunoassay, intracellular cAMP by protein binding assay,
      intracellular calcium in fura-2 loaded single cells using
      microspectrofluorimetry, and calcium channel activity by patch clamp technique.
      The adenosine A1 receptor analogue N-6 phenylisopropyl-adenosine (PIA) (10(-10)
      10(-6) M) inhibits dose-dependently glucagon (10(-7) M) and rGRH (10(-7) M)
      stimulated cAMP formation and calcitonin secretion. These effects were partly
      abolished by pretreatment with pertussis toxin (PT) (100 ng/ml). PIA (10(-10)-10(
      6) M) also suppressed extracellular calcium-stimulated calcitonin secretion,
      rises in intracellular calcium, and calcium channel currents. PT (100 ng/ml)
      pretreatment again partly abolished this inhibitory effect. The addition to the
      medium of adenosine deaminase (0.4 U/ml) stimulated calcitonin secretion. Our
      results suggest that in calcitonin-secreting cells A1 receptors couple to
      adenylate cyclase and calcium channels via PT-sensitive G proteins and thus
      inhibit calcitonin secretion. Adenosine seems to act as an autocrine/paracrine
      factor in calcitonin-secreting cells.

PMID- 8557240
TI  - Endogenous nitric oxide is not involved in acute parathyroid hormone-induced
      hypotension in rat: effect of hypertension and hypoparathyroid status.
AB  - The present study investigated the acute hypotensive effect of parathyroid
      hormone (PTH) in anesthetized adult spontaneously hypertensive (SHR) and
      normotensive Wistar-Kyoto rats. Furthermore, in order to determine the possible
      contribution of nitric oxide (NO), a mediator of endothelium-dependent
      vasorelaxation, hypotensive responses to PTH were obtained in the presence of NG
      nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis. The
      hypotensive effect of PTH (expressed as % of baseline blood pressure) was similar
      for the two strains. In the presence of L-NAME (18.5 mumol/kg), both strains
      demonstrated a similar hypotensive response to PTH, indicating that the
      hypotensive response to PTH is NO-independent.

PMID- 8557241
TI  - Correlations between lipid peroxide and glutathione levels in vitamin C
      supplemented fasting guinea pigs.
AB  - The object of this study was to investigate correlations between lipid peroxide
      (MDA) and glutathione (GSH) levels in liver, kidney, heart and brain of guinea
      pigs during fasting (24 h, 48 h, 120 h) and respectively by supplementation (A
      single dose, 500 mg/kg bw, ip) of vitamin C (AA, Ascorbic acid) on fasting (24 h,
      48 h, 120 h). MDA and GSH levels of various tissues by fasting and AA
      supplemented fasting were dependent on the function of each tissue during the
      fasting period. Lipid peroxide (LP) levels of kidney, heart and brain decreased
      for the AA supplemented fasting period. However, LP levels of liver increased in
      the AA supplemented 48 h and 120 h fasting groups. GSH levels of all tissues were
      affected differently in all of the AA supplemented fasting periods.

PMID- 8557242
TI  - Insulinkinetic and -dynamic in diabetic patients under insulin pump therapy after
      injections of human insulin or the insulin analogue (B28Asp).
AB  - In this double blind randomized study we compared the insulinkinetic,
      insulindynamic and the frequency of hypoglycemic events after s.c. injection of
      human insulin and the insulin analogue (B28Asp). Fourteen c-peptide negative
      patients treated with continuous subcutaneous insulin infusion (CSII) were
      included in the study. Their mean age was 42.9 (range 26-60 yrs), duration of
      diabetes 18.5 (5-29) and mean duration of CSII 6.3 yrs (3-10). Serum free insulin
      (FIRI) was determined from 8:00 to 11:00 h, and blood glucose from 7:00 to
      midnight. Maximum FIRI values were obtained after 45 min for (B28Asp) and after
      90 min for Actrapid HM. Maximum blood glucose increase (Tmax) was obtained 60 min
      after injection of (B28Asp) and 90 min after Actrapid HM. The AUCBC was greater
      after administration of Actrapid HM compared to (B28Asp) (p < or = 0.05). A total
      number of 16 hypoglycemias (BG < or = 3.3 mmol.l-1) were registered. 8 episodes
      were induced equally by (B28Asp) and by Actrapid HM. We conclude that in insulin
      dependent diabetic patients the insulin analogue (B28Asp) showed a faster
      absorption and less hyperinsulinemia than Actrapid HM after s.c. administration.
      The corresponding BG-values were higher after s.c. administration of Actrapid HM
      compared to (B28Asp). These findings in patients support the concept of a more
      physiological effect of rapid acting insulin analogues than of regular insulin.

PMID- 8557243
TI  - Pre- and postoperative investigations of hepatic glucose production and leucine
      turnover in Cushing's disease utilizing stable isotope techniques.
AB  - Impairment of glucose tolerance and muscle wasting indicating a disorder of
      glucose metabolism are characteristic features of Cushing's syndrome. We have
      examined glucose and amino acid metabolism in eleven patients with pituitary
      dependent Cushing's disease in comparison to nine healthy controls. Furthermore,
      the therapeutic effect of selective pituitary microsurgery was studied by
      repeated stable isotope measurements of hepatic glucose production and leucine
      turnover rates. Eight patients remitted after surgery and 3 had persistent
      disease. All patients were investigated prior to surgery and again 1 week and 3
      months after the operation with (6,6-2H2)-glucose and (5,5,5-2H3)-leucine by
      means of a primed (4 mg/kg.min and 0.27 mg/kg.min), continuous (0.05 mg/kg.min
      and 0.005 mg/kg.min) infusion. In Cushing's disease, both the preoperatively
      elevated mean glucose production rate (2.34 +/- 0.63 mg/kg.min) and the reduced
      mean leucine turnover (0.213 +/- 0.025 mg/kg.min) were found to be linked with
      hepatic insulin resistance and an insulin-induced reduction in protein breakdown
      combined with a reduced protein synthesis. Mean glucose production and leucine
      flux both normalized after surgery in the remitting patients (2.18 +/- 0.15
      mg/kg.min and 0.244 +/- 0.047 mg/kg.min 3 months after the operation). The
      metabolic disorders thus were reversible following successful correction of
      hormonal oversecretion by transsphenoidal surgery.

PMID- 8557244
TI  - Osteopenia in primary and secondary amenorrhea.
AB  - This study aimed at investigating the prevalence of osteopenia among a
      hypoestrogenic group of patients with primary or secondary amenorrhea. Twenty
      seven patients with amenorrhea were examined. Sixteen of them presented with
      secondary amenorrhea (mean age 27.8 +/- 1.9 yrs), and 11 with primary amenorrhea
      (mean age 21.3 +/- 1.6 yrs). Ten regularly menstruating women (mean age 28.9 +/-
      1.4 yrs) served as controls. Estradiol serum levels as well as lumbar spine bone
      mineral density were measured. All 11 patients with primary amenorrhea showed
      osteopenia with a mean bone mineral density Z-score of 71 +/- 2% and mean
      estradiol levels of 30.6 +/- 5.9 pg/ml. The secondary amenorrheic patients were
      significantly demineralized with a mean Z-score of 82 +/- 3%; 10 of them had
      osteopenia. Their mean estradiol levels were 34.3 +/- 2.9 pg/ml. The bone density
      in the primary amenorrheic patients was significantly lower as compared with the
      secondary amenorrheic women. In comparison, lumbar spine bone density in all
      control women was normal with a mean Z-score of 104 +/- 3%. In summary, 21 of the
      27 patients had osteopenia, higher than that reported in post-menopausal women.
      Since it is not proven whether the bone mineral deficit of amenorrheic patients
      can ever be compensated, early diagnostic steps and estrogen-progestogen
      replacement for the prevention of further bone loss and subsequent fractures are
      recommended.

PMID- 8557245
TI  - Steroid drug delivery systems in endocrine and metabolic research: evaluation of
      three models.

PMID- 8557246
TI  - Acromegaly with cavernous haemangioma of the liver and colonic polyps.

PMID- 8557247
TI  - Telomere elongation observed in immortalized human fibroblasts by treatment with
      60Co gamma rays or 4-nitroquinoline 1-oxide.
AB  - Telomeres are the tandemly repeated (TTAGGG)n sequences that make up the
      structural and functional ends of all chromosomes in mammals. Many lines of
      evidence indicate that telomeres stabilize chromosomes, prevent aberrant
      recombination, and direct chromosome attachment to the nuclear membrane. Since
      DNA polymerase requires a labile primer to initiate unidirectional 5'-3' DNA
      synthesis, some bases at the 3' end of each template strand are not copied unless
      special mechanisms bypass this end-replication problem. To overcome this problem,
      most eukaryotic cells use telomerase, an enzyme that elongates telomeres.
      However, this enzyme has not been detected in normal human cells, and these cells
      lose telomeres with cell division. Cellular senescence might be the result of
      this loss. Thus, activation of telomerase seems to be critical for the
      immortalization of human cell lines. In addition, substantial evidence indicates
      that immortalization in itself is a rate-limiting step for the malignant
      transformation of human cells. We have treated normal human fibroblasts (AD387,
      KMS-6, and OUMS-24 lines) intermittently with either 60Co gamma rays or 4
      nitroquinoline 1-oxide (4NQO) during serial subcultivations, and have obtained
      three immortalized cell lines, SUSM-1, KMST-6, and OUMS-24F. In KMS-6 and OUMS
      24, the mean terminal restriction fragment length significantly decreased as the
      population-doubling level increased. The rate of telomere loss was 40 and 50
      bp/population doubling in the KMS-6 and OUMS-24 cell lines, respectively. Once
      these normal cell lines were immortalized, their telomeres became elongated.
      Similar data were obtained for AD387 cells and their immortalized SUSM-1 cells.
      These results suggest that telomeres play a critical role in cellular senescence
      and in the immortalization processes of human cells.

PMID- 8557248
TI  - Linkage disequilibrium and extended haplotypes in the HLA-A to D6S105 region:
      implications for mapping the hemochromatosis gene (HFE).
AB  - The hemochromatosis gene (HFE) maps to 6p21.3, in close linkage with the HLA
      Class I genes. Linkage disequilibrium (LD) studies were designed to narrow down
      the most likely candidate region for HFE, as an alternative to traditional
      linkage analysis. However, both the HLA-A and D6S105 subregions, which are
      situated 2-3 cM and approximately 3 Mb apart, have been suggested to contain HFE.
      The present report extends our previous study based upon the analysis of a large
      number of HFE and normal chromosomes from 66 families of Breton ancestry. In
      addition to the previously used RFLP markers spanning the 400-kb surrounding HLA
      A, we examined three microsatellites: D6S510, HLA-F, and D6S105. Our combined
      data not only confirm a peak of LD at D6S105, but also reveal a complex pattern
      of LD over the i82 to D6S105 interval. Within our ethnically well-defined
      population of Brittany, the association of HFE with D6S105 is as great as that
      with HLA-A, while the internal markers display a lower LD. Fine haplotype
      analysis enabled us to identify two categories of haplotypes segregating with
      HFE. In contrast to the vast majority of normal haplotypes, 50% of HFE haplotypes
      are completely conserved over the HLA-A to D6S105 interval. These haplotypes
      could have been conserved through recombination suppression, selective forces
      and/or other evolutionary factors. This particular haplotypic configuration might
      account for the apparent inconsistencies between genetic linkage and LD data, and
      additionally greatly complicates positional cloning of HFE through disequilibrium
      mapping.

PMID- 8557249
TI  - Mutation analysis of the RET proto-oncogene in Dutch families with MEN 2A, MEN 2B
      and FMTC: two novel mutations and one de novo mutation for MEN 2A.
AB  - Hereditary C-cell carcinoma is encountered in multiple endocrine neoplasia type
      2A (MEN 2A), MEN 2B, and familial medullary thyroid carcinoma (FMTC). Mutations
      of the RET proto-oncogene are associated with all three diseases. To obtain an
      insight into the molecular heterogeneity of MEN 2 syndromes and FMTC in the
      Netherlands, probands of 20 MEN 2A families, two FMTC families, and seven MEN 2B
      families were analyzed by the polymerase chain reaction (PCR), DNA sequencing,
      and restriction enzyme digestion for abnormalities in the RET proto-oncogene. RET
      mutations were found in all cases. All MEN 2A families had a mutation involving
      one of five cysteine codons in exons 10 and 11 of RET. Two novel dinucleotide
      mutations and a de novo mutation were found. Both FMTC families had a mutation of
      the Cys at codon 618. All MEN 2B probands carried a Met to Thr mutation in exon
      16. All mutations could be confirmed by restriction enzyme digestion of PCR
      amplicons. Identification of the RET mutation in the Dutch population with
      hereditary C-cell carcinoma facilitates genetic testing for families or
      individuals at risk for MEN 2A, FMTC, and MEN 2B.

PMID- 8557250
TI  - Isolation and characterization of the human mismatch repair gene hMSH2 promoter
      region.
AB  - Hereditary nonpolyposis colorectal cancer (HN-PCC) is one of man's commonest
      hereditary diseases. Several studies have identified four responsible genes that
      are involved in a process known as DNA mismatch repair; hMSH2 is the most
      important of these four genes. In addition to mutational analysis of these genes,
      investigations of transcriptional regulatory mechanisms are important. Therefore,
      our purpose has been to isolate the hMSH2 promoter region. Using direct
      sequencing of P1 recombinant DNA we have characterized 1100 bp of the hMSH2
      promoter.

PMID- 8557251
TI  - Characterisation of a short interspersed repeat (Mermaid) that has family members
      on human chromosome 21 and elsewhere in the human genome.
AB  - To understand the architecture of the human genome, we need a complete definition
      of all the repeat sequence families, as these make up the majority of human DNA.
      We have isolated a small DNA fragment from human chromosome 21 and have used
      sequence analysis of this fragment to uncover a new low copy repeat element of
      approximately 300 bp that we term the Mermaid repeat. This repeat is related to,
      but is different from, the MER12 repeat and is interspersed in the genome.
      Mermaid family members that we have studied are between 81%-87% identical to our
      preliminary consensus sequence. Therefore, we have added a new member to the
      large collection of human repetitive elements. In addition, we have mapped a
      Mermaid repeat to a telomeric position on the long arm of human chromosome 21, at
      21q22.3.

PMID- 8557252
TI  - Identification of three neurofibromatosis type 2 (NF2) gene mutations in
      vestibular schwannomas.
AB  - Vestibular schwannomas (VSs) are common benign tumors of Schwann cell origin and
      are frequently found in patients with neurofibromatosis type 2 (NF2). We analyzed
      15 sporadic VSs for mutations in the tumors, two of which contained loss of
      heterozygosity (LOH). One of the tumors contained a novel mutation, a 19-bp
      deletion in exon 4. The two other tumors contained an identical mutation, a
      complete exon 4 deletion. The exon 4 deletion represents the second most
      frequently reported mutation of the NF2 gene in VSs.

PMID- 8557253
TI  - A highly polymorphic CA/GT repeat in intron 3 of the human urokinase receptor
      gene (PLAUR).
AB  - We describe the first highly polymorphic microsatellite marker for the human
      urokinase plasminogen activator receptor gene (PLAUR). The urokinase receptor
      (uPAR) has a central role in cancer invasion and metastasis, which may enable the
      development of new anti-metastatic therapies. Analysis of the marker genotypes in
      colorectal cancer cell lines revealed three alleles that were not detected in a
      series of healthy control individuals, which encourages further genetic study of
      the role of uPAR in cancer.

PMID- 8557255
TI  - Direct detection of disomy in human sperm by the PRINS technique.
AB  - We report the use of the PRimedIN Situ (PRINS) labelling technique for the direct
      estimation of disomy rates for various chromosomes in human sperm. The PRINS
      technique provides a rapid and reliable method for chromosome screening since
      specific labelling may be obtained in less than 2 h. In the present study, the
      disomy rates of chromosomes 2, 5, 9, 12 and 18 were investigated. The incidences
      of disomy are similar for all these chromosomes, ranging from 0.27% to 0.33%.
      These findings suggest an equal distribution of aneuploidies among autosomes in
      human sperm.

PMID- 8557254
TI  - DNA polymorphisms in adhesion molecule genes--a new risk factor for early
      atherosclerosis.
AB  - To contribute to the analysis of the genetic background of atherosclerosis,
      especially endothelial dysfunction, we searched for DNA polymorphisms in the
      genes encoding E-, P-, and L-selectin, and ICAM-I and VCAM-I. We detected 17
      mutations by single-strand conformation polymorphisms analysis and direct
      sequencing. Five of them resulted in an amino acid substitution. In E-selectin,
      exchanges from serine to arginine (position 128), from leucine to phenylalanine
      (position 554), and a DNA mutation from guanine to thymine (position 98) present
      significantly different allele frequencies in young patients with
      angiographically established, severe atherosclerosis, compared with an unselected
      population. Results suggest that these polymorphisms are associated with a higher
      risk for early severe atherosclerosis.

PMID- 8557256
TI  - Molecular genetic analysis of the 17p11.2 region in patients with hereditary
      neuropathy with liability to pressure palsies (HNPP).
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is in most cases
      associated with an interstitial deletion of the same 1.5-Mb region at 17p11.2
      that is duplicated in Charcot-Marie-Tooth type 1A (CMT1A) patients. Unequal
      crossing-over following misalignment at flanking repeat sequences (CMT1A-REP),
      either leads to tandem duplication in CMT1A patients or deletion in HNPP
      patients. With the use of polymorphic DNA markers located within the CMT1A/HNPP
      duplication/deletion region we detected the HNPP deletion in 16 unrelated HNPP
      patients, 11 of Belgian and 5 of French origin. In all cases, the 1.5-Mb size of
      the HNPP deletion was confirmed by EcoRI dosage analysis using a CMT1A-REP probe.
      In the 16 HNPP patients, the same 370/320-kb EagI deletion-junction fragments
      were detected with pulsed field gel electrophoresis (PFGE), while in CMT1A
      patients, a 150-kb EagI duplication-junction fragment was seen. Thus, PFGE
      analysis of EagI-digested DNA with a CMT1A-REP probe allows direct detection of
      the HNPP deletion or the CMT1A duplication for DNA diagnostic purposes.

PMID- 8557257
TI  - A novel mutation in exon 17 of the beta-subunit of rod phosphodiesterase in two
      RP sisters of a consanguineous family.
AB  - We report the molecular analysis of the beta subunit of the rod phosphodiesterase
      (PDEB) gene in a consanguineous autosomal recessive retinitis pigmentosa family
      that shows homozygosity for polymorphisms in the genomic region comprising this
      gene, and positive linkage between a PDEB marker and the disease. The two
      affected sisters are homozygous for a T to G transversion in codon 699 of the
      PDEB gene, leading to the substitution of a leucine by an arginine residue. This
      change, enclosed in the catalytic domain of the PDEB, could result in a
      modification of the protein structure preventing the physiological hydrolysis of
      cGMP.

PMID- 8557258
TI  - Ullrich-Turner syndrome is not caused by haploinsufficiency of RPS4X.
AB  - Ullrich-Turner syndrome (UTS) is frequently associated with monosomy X but may
      also occur with structural aberrations of the X and the Y chromosomes. It has
      been hypothesized that the ribosomal protein genes RPS4X and RPS4Y play a
      critical role in the prevention of UTS. Individual patients with a 46,X,i(Xq)
      karyotype cannot be differentiated phenotypically from 45,X UTS patients and
      carry three gene copies of RPS4X. Since haploinsufficiency of one or several
      gene(s) is thought to cause the UTS phenotype, direct assessment of RPS4X
      expression levels in these patients should establish whether RPS4X is involved in
      UTS. We have investigated fibroblasts of four 46,X,i(Xq) UTS patients with
      typical symptoms and a non-mosaic chromosome complement, and have found
      significantly increased RPS4X mRNA levels in all patients. Based on our results,
      we conclude that haploinsufficiency of RPS4X is not the cause of UTS.

PMID- 8557259
TI  - Identification of three novel mutations in the PIG-A gene in paroxysmal nocturnal
      haemoglobinuria (PNH) patients.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic disorder
      caused by the absence of glycosyl phosphatidylinositol (GPI)-anchored surface
      proteins resulting from a defect in one step of GPI-anchor biosynthesis. Recent
      analysis has shown that mutations at the PIG-A (phosphatidylinositoglycan-class
      A) gene are responsible for GPI-anchor deficiency in all PNH patients. In the
      current study, we describe three new mutations of the PIG-A gene in Italian
      patients with PNH. The analysis has been performed by RNA/single-strand
      conformation polymorphism using genomic DNA purified from nucleated peripheral
      blood cells. An abnormal pattern of migration of polymerase chain reaction
      amplified fragments containing exons 2 and 5 was observed. Sequencing analysis
      led to the identification of three mutations: a transversion C-to-A creating a
      stop codon (Y98X), an A insertion at position 460 (460insA), and a C deletion
      (1114delC). All the mutations cause a premature termination of the translation of
      the PIG-A protein.

PMID- 8557260
TI  - Mean corpuscular hemoglobin is not increased in Fmr1 knockout mice.
AB  - A slight increase in mean corpuscular hemoglobin (MCH) has been reported in
      erythrocytes from human fragile X patients. As it is difficult to perform case
      controlled studies in patients with fragile X syndrome, we studied MCH in
      erythrocytes from transgenic mice with an Fmr1 knockout. None of the knockout
      mice showed increased MCH levels when compared with normal littermates. We
      conclude that it is unlikely that the FMR1 gene product has an effect on MCH.

PMID- 8557261
TI  - Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus
      mutations in the human fumarylacetoacetate hydrolase gene; variability of the
      genotype-phenotype relationship.
AB  - The complete fumarylacetoacetate hydrolase (FAH) genotype of probands of thirteen
      unrelated families with hereditary tyrosinemia type 1 (HT 1) was established. The
      screening was performed by analysis of exons 2-14 of the FAH gene by using the
      polymerase chain reaction (PCR) and of the mRNA by reverse transcription/PCR.
      Nine different mutations were identified, of which six are novel. Three mutations
      involve consensus sequences for correct splicing, viz. IVS 6-1 (g-t), IVS 7-1 (g
      a) and IVS 12 + 5 (g-a). Two missense mutations (C193R and G369V) and three
      nonsense mutations (R237X, E357X and E364X) were found. One silent mutation N232N
      was associated with the skipping of exon 8 from the FAH mRNA. Analysis of the
      effect of the respective mutations on the FAH mRNA showed a strong reduction of
      FAH mRNA levels in association with the nonsense mutations, and normal levels
      with the missense mutations. The splice consensus mutations give deletions of
      complete or small parts of exon sequences from the FAH mRNA. Data suggest a
      founder effect for several of the mutations, with a frequency for both the IVS 6
      1 (g-t) and IVS 12 + 5 (g-a) mutations of approximately 30% in the HT 1 probands.
      No strict correlation between genotype and phenotype, i.e. the acute, subacute or
      chronic form of HT 1, was evident.

PMID- 8557262
TI  - Construction of a YAC contig and an STS map spanning 3.6 megabase pairs in
      Xp22.1.
AB  - We have constructed a 3.6 Mb sequence tagged sites (STS)-based yeast artificial
      chromosome (YAC) contig, consisting of 58 individual YAC clones, spanning the
      region PDHA1 and DXS451 on Xp22.1. In addition to establishing the order of
      PDHA1, ISPK-1, DXS2504, DXS1528 and the 13 known polymorphic loci as Xpter-PDHA1
      DXS443-DXS3424-ISPK-1-DXS12 29-DXS2504-DXS1528-DXS365-DXS7101- DXS1683-DXS1052
      DXS274-DXS92-DXS1226-DX S41-DXS989-DXS451-Xcen, we have also developed 35 novel
      STSs from YAC end clones. These results provide a high density of STS markers
      (approximately 1 per 70 kb). Furthermore, a detailed long-range restriction map
      of the contig has been constructed with rare-cutter enzymes and this has refined
      and verified the physical distances between markers inferred from YAC sizes and
      their STS content. The integration of the physical mapping data with previous
      genetic mapping data and the use of STSs and non-chimeric YAC clones reported
      here should facilitate the construction of a transcript map of this region and
      the positional cloning of disease genes in this portion of Xp22.1.

PMID- 8557263
TI  - A clinical and molecular study of mosaicism for trisomy 17.
AB  - Trisomy 17 has never been reported in a live birth. We present a case of mosaic
      trisomy 17 in a male presenting with mental retardation, seizures, attention
      deficit hyperactivity and autistic disorders, hearing loss, growth retardation,
      microcephaly, and minor anomalies. Although peripheral blood lymphocyte
      chromosomes were normal, trisomy 17 was present in the skin fibroblasts. The
      percentage of abnormal cells appears to have increased from 18% in an initial
      skin biopsy at age 3 years 8 months to 80% at age 8 years 8 months. Molecular
      analysis using 13 highly polymorphic markers spanning the length of chromosome 17
      demonstrated the extra chromosome 17 in the skin to be of paternal origin. Three
      alleles were never seen in the trisomic cell line, suggesting that the extra
      chromosome arose through a mitotic duplication error after conception.
      Uniparental disomy was excluded in the euploid blood sample. Although Smith
      Magenis syndrome involves a deletion of proximal 17p, some of the clinical
      features of this mosaic trisomy 17 patient, such as decreased REM sleep and
      increased tolerance to pain, are suggestive of phenotypic features observed in
      Smith-Magenis syndrome. We speculate that there are dosage-sensitive genes
      located in 17p11.2 that produce these phenotypes for either deficiencies or over
      expression of their gene products.

PMID- 8557264
TI  - Congenital bilateral absence of the vas deferens (CBAVD) and cystic fibrosis
      transmembrane regulator (CFTR): correlation between genotype and phenotype.
AB  - To assess better the link between congenital bilateral absence of the vas
      deferens (CBAVD) and cystic fibrosis (CF), we compared sweat chloride values,
      analysis of the CFTR intron 8 poly(T) tract length and analysis of 10 exons in a
      population of 38 patients with CBAVD. The data indicate that this population can
      be divided into three groups of patients. In the first group of 15 patients with
      abnormal sweat chloride (> 60 mmol/l), the frequency of CF mutations is high. In
      the second group of 18 patients with equivocal sweat chloride (between 40 and 60
      mmol/l), the frequency of the 5T variant is high; 6 patients have a delta F508
      mutation and a 5T variant and 1 patient is homozygous for the 5T variant; a 5T
      variant has been detected in 3 other patients, and a delta F508 mutation in
      another patient. A third group of 5 patients is probably not related to CF: these
      patients have other congenital abnormalities of the urogenital tract, low
      chloride values (< 40 mmol/l) and apparently no abnormality of the CF gene.

PMID- 8557265
TI  - Pseudohypoparathyroidism type Ia: two new heterozygous frameshift mutations in
      exons 5 and 10 of the Gs alpha gene.
AB  - Pseudohypoparathyroidism type Ia (PHP-Ia) is a hereditary disease characterized
      by resistance to PTH and other hormones that act via cAMP. Patients have
      deficient activity of Gs alpha, the alpha subunit of the G protein, which couples
      hormone receptors to stimulation of adenylate cyclase. We describe two new
      mutations discovered in two sporadic patients with PHP-Ia. Using genomic DNA, we
      have amplified exons 2-13 of the Gs alpha gene (GNAS1) by PCR, and sequenced the
      resulting products. Both patients had Albright's hereditary osteodystrophy,
      resistance to multiple hormones, and deficient Gs alpha activity. In the first
      patient, a deletion of a C in exon 5 at codon 115 was found. In the second
      patient, an insertion of a C in exon 10 at codon 267 was detected. Both these
      heterozygous mutations cause frameshift, and predict decreased production of Gs
      alpha. This report adds two new Gs alpha mutations to the known ten mutations
      recently described.

PMID- 8557266
TI  - Molecular re-investigation of patients with Huntington's disease in Wessex
      reveals a family with dentatorubral and pallidoluysian atrophy.
AB  - Dentatorubral and pallidolysian atrophy (DRPLA), a neurological disorder thought
      to be rare in European populations, is caused by a triplet repeat expansion in
      the B37 gene on chromosome 12. This disorder can phenotypically mimic
      Huntington's disease (HD) which is also caused by a repeat expansion. We have
      analysed 139 affected individuals for the HD triplet repeat expansion and found
      132 patients had one normal and one expanded allele. Two patients had an
      expansion on both chromosomes and five patients had two normal-size alleles. Of
      these five patients, two were considered to be atypical Two patients who were
      father and daughter were found to have an expansion of the DRPLA triplet repeat.
      This therefore constitutes the second such family described in the United
      Kingdom.

PMID- 8557268
TI  - A novel site of DNA amplification on chromosome 1p32-33 in a rhabdomyosarcoma
      revealed by comparative genomic hybridization.
AB  - Cytogenetic analysis of a human embryonal rhabdomyosarcoma revealed a near
      diploid karyotype with structural chromosome aberrations not involving the
      typical rearrangements of rhabdomyosarcomas, plus a large number of double
      minutes. Comparative genomic hybridization revealed a previously undescribed site
      of DNA amplification on the short arm of chromosome 1 (band 1p32-33).

PMID- 8557267
TI  - Xp-duplications with and without sex reversal.
AB  - Duplications in Xp including the DSS (dosage sensitive sex reversal) region cause
      male to female sex reversal. We investigated two patients from families with Xp
      duplications. The first case was one of two sisters with karyotype
      46,XY,der(22),t(X;22)(p11.3;p11)mat and unambiguous female genitalia. The living
      sister was developmentally retarded, and showed multiple dysmorphic features and
      an acrocallosal syndrome. The second case was a boy with a maternally inherited
      direct duplication of Xp21.3-pter with the breakpoint close to the DSS locus. He
      had multiple abnormalities and micropenis, but otherwise unambiguous male
      genitalia. We performed quantitative Southern blot analysis with probes from
      Xp22.13 to p21.2 to define the duplicated region. Clinical, cytogenetic, and
      molecular data from both patients were compared with those of previously reported
      related cases. A comparison of the extragenital symptoms revealed no differences
      between patients with or without sex reversal. In both cases, the symptoms were
      non-specific. Among 22 patients with a duplication in Xp, nine had unambiguous
      female genitalia and a well-documented duplication of the DSS region. Two
      patients with duplication of DSS showed ambiguous external genitalia. From these
      data, we conclude that induction of testicular tissue may start in these
      patients, but that the type of genitalia depends on the degree of subsequent
      degeneration by a gene in DSS.

PMID- 8557270
TI  - Precise chromosomal locations of the genes for dentatorubral-pallidoluysian
      atrophy (DRPLA), von Willebrand factor (F8vWF) and parathyroid hormone-like
      hormone (PTHLH) in human chromosome 12p by deletion mapping.
AB  - The precise chromosomal localization of the gene for dentatorubral-pallidoluysian
      atrophy (DRPLA) was detected by deletion mapping. Segregation patterns of
      genotypes of polymerase chain reaction products of DRPLA, von Willebrand factor
      (F8vWF), antigen CD4(p55) (CD4) and parathyroid hormone-like hormone (PTHLH) loci
      were studied in patients with del(12)(p13.3p13.3), del(12)(p12.3-p11.2),
      del(12)(p12.1-p11.2), del(12) (p11.2p11.2) and their parents. The gene for DRPLA
      was assigned to p13.1-p12.3 of chromosome 12. In addition, genes for F8vWF and
      PTHLH were mapped to p13.2 and p11.2 of chromosome 12, respectively.

PMID- 8557269
TI  - Mutational analysis of the human cyclin-dependent kinase inhibitor p27kip1 in
      primary breast carcinomas.
AB  - The human p27kip1 gene encodes a cyclin-dependent kinase inhibitor implicated in
      the negative regulation of the cell cycle. In order to elucidate the possible
      role of p27 mutations in the development or progression of human breast cancer,
      we have studied the occurrence of genetic abnormalities in this gene in a series
      of 30 primary breast carcinomas. Direct sequence analysis of the polymerase chain
      reaction amplified human p27 gene revealed the occurrence of two sequence
      variations with respect to the reported sequence; both variants were also present
      in the lymphocyte DNA from the same patients. First, a silent G to A change at
      codon 142 (Thr) was detected in a single case. Second, a T to G transversion at
      codon 109, resulting in a Val to Gly change, was observed in eight tumour DNA
      samples (26%) and in 31 out of 80 unrelated normal individuals (39%). This latter
      change creates a Bg/I restriction site that might be useful for genetic analysis
      of human tumours. Despite the occurrence of these polymorphisms, we did not
      however find any evidence of somatic mutations in the coding region of the p27
      gene. On the basis of these results, we suggest that alterations in the integrity
      of the human p27 gene are not common events in human breast carcinomas.

PMID- 8557271
TI  - Apparent higher frequency of phenylketonuria in the Mexican state of Jalisco.
AB  - The geographic origin of Mexican patients with phenylketonuria (PKU) in Mexico
      City and in southern California was studied. Compared to patients with other
      metabolic disorders, patients with PKU were significantly more likely to have
      originated from the Los Altos region of the state of Jalisco and its environs.
      The incidence of PKU among mentally retarded students attending special education
      schools was found to be significantly higher in Jalisco (particularly the Los
      Altos region) than in the neighboring state of Guanajuato (1.09% vs 0.3%). These
      results strongly suggest a "population of origin" effect, the mutant allele(s)
      having been introduced by the Spanish ancestors of the current population. Our
      findings also support the addition of PKU to the neonatal screening program for
      this region of Mexico.

PMID- 8557272
TI  - Ischemic preconditioning and myocardial protection.

PMID- 8557273
TI  - Current trends in cardiac transplantation.

PMID- 8557275
TI  - Prevalence of coronary heart disease in India: a contemporary view.

PMID- 8557274
TI  - Prevalence of coronary heart disease and coronary risk factors in an urban
      population of Rajasthan.
AB  - To determine the prevalence of coronary heart disease (CHD) and coronary risk
      factors in an urban Indian population, we studied a random sample of population
      of Jaipur. A physician-administered questionnaire, physical examination and a 12
      lead electrocardiogram was performed on 2,212 adults of > or = 20 years of age
      (males 1,415, females 797). CHD was diagnosed on the basis of past documentation,
      response to WHO-Rose questionnaire or changes in the electrocardiogram. The
      overall prevalence of CHD was 7.6 percent (168 cases). The prevalence rate was
      6.0 percent (84) in males and 10.4 percent (84) in females with an age-related
      increase in prevalence ('p' for trend < 0.001). When diagnosed on the basis of
      electrocardiographic changes alone (Q, ST or T wave), the prevalence was 5.2
      percent (116), with 3.5 percent in males and 8.4 percent in females. CHD was
      silent in 57 percent males and 79 percent females. Coronary risk factors were
      observed in a significant proportion: smoking in 32 percent (males 39 percent,
      females 19 percent), hypertension (> or = 140/90 mm Hg) in 31 percent (males 30
      percent, females 34 percent-JNC-V) and > or = 160/95 mm Hg in 11 percent (males
      10 percent, females 12 percent; WHO classification), diabetes in 1 percent and
      sedentary habits in 71 percent. Additional risk factors were generalised obesity
      (body-mass index > or = 27 Kg/m2) in 11 percent and truncal obesity (waist-hip
      ratio > 0.95) in 17 percent males and 13 percent females. Significant association
      of CHD prevalence were seen with age, sedentary habits and presence of
      hypertension in both males and females, and in addition with smoking in males.

PMID- 8557276
TI  - Angiographic severity and morphological spectrum of coronary artery disease in
      non insulin dependent diabetes mellitus.
AB  - Coronary angiographic profile of 75 patients (63 males and 12 females) with
      noninsulin dependent diabetes mellitus (NIDDM) and CAD was compared with 75
      nondiabetic patients (63 males and 12 females) with CAD. No difference was
      present between the mean age (56.2 +/- 7.4 vs 56.1 +/- 7.7 years; p = NS),
      presenting complaints (67 unstable angina and 8 stable angina with positive TMT
      in both the groups) and other coronary risk factors between the two groups.
      Severity and diffuseness of coronary artery involvement was assessed by a
      coronary artery score (CAS) using the segmental distribution method for coronary
      artery lesions. Diabetic patients with CAD had a higher CAS (18.7 +/- 10.3) as
      compared to the nondiabetic patients with CAD (12.7 +/- 9.6) (p < 0.01). Diabetic
      patients with CAD had a higher number of TVD [43 (57.3%) vs 31 (41.3%); p < 0.01]
      while the DVD and SVD was not significantly different. As compared to the
      nondiabetic group, diabetics had a higher total number of coronary artery lesions
      (300 vs 200; p < 0.001), a higher lesion per patient ratio (4.0 lesions/patient
      vs 2.6 lesions/patient; p < 0.001), a higher number of concentric lesions, [151
      (50.3%) vs 90 (45%); p < 0.01] and a higher number of multiple irregularity
      lesions, [36 (21%) vs 27 (9%); p < 0.05]. The diffuse involvement of vessels was
      not significantly different between the two groups in LAD (12.1% vs 5.3%; p =
      NS), LCx (14.2% vs 5.8%; p = NS) and RCA (10.5% vs 5.0%; p = NS).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8557277
TI  - Predischarge dobutamine induced distant wall motion abnormalities after acute
      myocardial infarction predict multivessel disease.
AB  - Presence of multivessel coronary artery disease (MVD) identifies a high risk
      subgroup after acute myocardial infarction (AMI). Dobutamine stress
      echocardiography (DSE) has recently emerged as a promising non invasive test to
      detect the presence and extent of coronary artery disease. Forty six consecutive
      patients (38 males, 8 females; mean age 48.6 +/- 10.4 years) of Q-wave acute
      myocardial infarction were subjected to submaximal treadmill test (TMT) and
      dobutamine stress echocardiography to see their ability to predict multivessel
      coronary artery disease as detected by coronary angiography before hospital
      discharge. Dobutamine infusion was started at 5 micrograms/kg/min to a maximum of
      40 micrograms/kg/min, to achieve 70 percent of the age predicted heart rate.
      Appearance of new regional wall motion abnormality was interpreted as positive
      DSE for MVD. Mean peak infusion dose of dobutamine used in the study was 28.56 +/
      5.67 micrograms/kg/min. In none of the patients, the test had to be terminated
      due to side effects. The sensitivity and specificity of DSE to predict MVD was 80
      percent and 93.7 percent, respectively as compared to 45 percent and 86 percent
      for submaximal TMT. Thus, DSE in patients of AMI before hospital discharge is a
      safe procedure with fairly accurate prediction of multivessel coronary artery
      disease.

PMID- 8557278
TI  - Signal-averaged electrocardiography in survivors of first acute myocardial
      infarction: a pre-hospital discharge study.
AB  - Ninety one consecutive survivors of a first acute myocardial infarction (MI) were
      studied prior to hospital discharge, in order to observe the relationship of
      signal-averaged electrocardiography (SAECG) to thrombolytic therapy, site of
      infarction and left ventricular function. Sixty six patients received
      thrombolytic agents and the remaining had conventional therapy. The overall
      incidence of abnormal SAECG was 27 percent and 16 percent with high-pass 40 Hz
      and 25 Hz filters respectively. The SAECG (40Hz) was abnormal in 12 of 25
      patients (48%) who did not receive thrombolytic therapy and in 13 of 66 (20%) who
      were thrombolysed (p < 0.01). When patients were classified according to the site
      of myocardial infarction, 6 out of 10 patients (60%) with anterior MI who were
      not thrombolysed had abnormal SAECG as compared to 10 of 51(20%) who received
      this treatment (p < 0.01), with no significant difference among inferior
      myocardial infarction patients. The mean (+/- SEM) ejection fraction (EF%) of
      anterior myocardial infarction patients was 31 +/- 3 percent in those with
      abnormal SAECG when compared to 39 +/- 2 percent in patients with normal SAECG (p
      < 0.05). Similarly, in patients with inferior myocardial infarction, the mean EF
      among these respective groups was 41 +/- 2 and 47 +/- 2 percent (p < 0.05). The
      mean echocardiographic score, which reflected regional LV wall motion
      abnormality, was not different between patients with anterior infarction when the
      groups with abnormal and normal SAECG were compared (9.1 +/- 0.6 versus 6.4 +/-
      0.4), but differed significantly between inferior infarction patients (5.8 +/-
      0.7 versus 4.6 +/- 0.4 respectively; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8557279
TI  - Immunohistochemical characterisation and quantitative evaluation of
      lymphomononuclear cells in dilated cardiomyopathy-an endomyocardial biopsy study.
AB  - Endomyocardial biopsies (EMB) from patients of dilated cardiomyopathy (DCM) and
      normal hearts were evaluated for infiltration by lymphomononuclear cells.
      Cryostat sections from cases of DCM were stained with antisera against leucocyte
      common antigen (LCA), Pan T lymphocytes and macrophages. Paraffin sections from
      patients of DCM and normal hearts were also stained with a panel of antisera
      against LCA, and macrophage markers namely, lysozyme, alpha-1-antitrypsin (AAT)
      and alpha-1-antichymotrypsin (ACT). The stained cells were quantitated and
      expressed as number of cells/mm2. Comparisons were made between the number of
      lymphomononuclear cells in hematoxylin and eosin stained sections and those
      stained by various markers. Light microscopic evaluation of paraffin sections of
      EMB in all cases of DCM showed mild to moderate hypertrophy of the myocardium in
      20 and 10 patients respectively. Only mild focal myonecrosis was observed in 14
      patients. These foci showed minimal infiltration by lymphomononuclear cells. In
      normal hearts, occasional small foci of lymphomononuclear cells were seen within
      the interstitium. The number of LCA positive cells in the frozen section from
      cases of DCM were more (7.03 +/- 3.15/mm2) than the number of cells in the
      corresponding paraffin sections (5.26 +/- 1.14/mm2), thus indicating that
      antigens are possibly better preserved in frozen sections. In normal hearts, the
      number of cells staining positively with LCA were almost identical (4.81 +/-
      1.14/mm2) to those seen in paraffin sections of cases of DCM (5.26 +/-
      1.61/mm2).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8557280
TI  - Primary angioplasty with elective coronary stenting in acute myocardial
      infarction.

PMID- 8557281
TI  - Clinical profile and management of post infarction left ventricular
      pseudoaneurysm.
AB  - Three patients with left ventricular pseudoaneurysm are presented. Two patients
      had inferior and one had an anterolateral wall Q wave myocardial infarction.
      Echocardiography with Doppler colour imaging provided the diagnosis in one case,
      whereas the correct diagnosis was possible on left ventriculography in all.
      Successful surgery using patch closure of the defect in all patients and bypass
      grafting of the diseased coronary vessels was done in 2 cases. Angiographic
      follow-up in one case revealed excellent result and during 18 to 30 months of
      clinical follow-up, all patients are asymptomatic.

PMID- 8557282
TI  - Common with the uncommon--atrial septal defect with hypertrophic cardiomyopathy.

PMID- 8557283
TI  - Prenatal diagnosis of tetralogy of Fallot with absent pulmonary valve.

PMID- 8557284
TI  - Intracardiac repair of obstructed right sided scimitar syndrome.

PMID- 8557285
TI  - New thrombin inhibiting strategies for coronary artery disease.

PMID- 8557286
TI  - Management of cardiac arrest survivors: drugs or devices.

PMID- 8557287
TI  - Present status of rheumatic fever and rheumatic heart disease in India.
AB  - This paper examines the present status of Rheumatic fever (RF) and Rheumatic
      heart disease (RHD) in India with reference to both prevalence and incidence, and
      evaluates the currently available methods of control. Data available over the
      last 10 years shows that the prevalence of RF/RHD in the most vulnerable group
      i.e. school children between 5 to 15 years of age is still unacceptably high. RHD
      is encountered in 1 to 5.4 per 1,000 in large samples of school children and RF
      in 0.3 to 0.5 per 1,000 children. There appears to be no obvious decline in its
      prevalence in school children over a 20 year period. Because of preoccupation
      with adult cardiac diseases specially ischemic heart disease (IHD), the problem
      of RF/RHD has been sidelined and studies on prevalence, treatment and prevention
      receive scant attention. Only exotic palliative methods such as balloon mitral
      valvotomy (BMV) have become the centre stage. Studies are needed on the lines of
      WHO recommendations for the regional prevalence of RF/RHD in school children
      throughout the country to detect regional variations. The most effective method
      for control is primary prevention by treating streptococcal sore throat and
      secondary prevention by early detection and continuous penicillin prophylaxis.
      This could be done most effectively by general physicians (GP's) who need
      motivation and education and through school health services. The latter needs to
      be organised on a state-wise basis throughout the country as it is available in
      only a few cities. Public health education by all available media specially,
      through video films is also recommended. The lacunae in our knowledge of RF/RHD
      calls for further research.

PMID- 8557288
TI  - Special features of coronary heart disease in people of the Indian sub-continent.
AB  - Contrary to the popular belief, coronary heart disease (CHD) is indeed common in
      the Indian sub-continent. Expatriate Indians in their newly adopted countries
      have 3 to 5 times more chance of developing CHD than the native population or the
      other immigrant groups. The well-known risk factors such as hypercholesterolemia,
      hypertension and smoking do not appear to play a major role, while the syndrome
      of insulin resistance seems to be an important risk factor for CHD in people of
      this sub-continent. Abdominal obesity, hypertriglyceridemia, and low plasma HDL
      cholesterol are the markers of this syndrome. Increased plasma insulin levels or
      even better, the C-peptide measurement may help in identifying the abnormality
      early. As CHD among Indians has been found to be severe and more diffuse with
      serious complications and increased mortality at a younger age, preventive
      measures need to be instituted early. Low fat and complex carbohydrate diet along
      with regular aerobic exercise may help reduce abdominal obesity, improve insulin
      sensitivity and HDL cholesterol levels. Hypertriglyceridemia uncontrolled by
      above measures may require pharmacotherapy with agents such as gemfibrozil.
      Smoking must be stopped to help reduce insulin resistance and improve HDL levels
      and endothelial function. Those with hypertension should be considered for
      therapy with ACE inhibitors, which may improve insulin sensitivity. In patients
      with insulin resistance, therapy with metformin or troglitazone may be helpful.

PMID- 8557289
TI  - Need for national hypertension control programme.

PMID- 8557290
TI  - Coexistence of mobitz type II AV block in a patient with WPW syndrome.

PMID- 8557291
TI  - Transposition of great vessels with rheumatic systemic atrioventricular valve
      regurgitation.

PMID- 8557292
TI  - Comparison of leads V4R and V1 in the electrocardiographic diagnosis of left
      atrial enlargement and right ventricular hypertrophy in mitral stenosis.

PMID- 8557293
TI  - A case cancer control study of reproductive in breast cancer.
AB  - The role of reproductive factors, such as, parity, age at menarche, age at first
      child's birth have been investigated in a hospital based case-control study, for
      their independent as well as combined influences on the incidence of female
      breast cancer. The study indicates that except for parity, these factors have no
      influence on the age at onset of the disease. Parity is positively correlated
      with age at onset. The patient and the control groups were found to be similar in
      respect of age at first child's birth and age at menarche, but the patient group
      was significantly lower both in parity and age at onset of the disease. Both
      these factors are negatively associated with the incidence of breast cancer.
      Therefore, preventive action should be focussed on young women with low parity.

PMID- 8557294
TI  - Cancer profile in eastern Rajasthan.
AB  - A study to determine the pattern of various malignancies in Eastern Rajasthan was
      conducted for the year 1990 by Cancer Registry, S.M.S. Medical College, Jaipur.
      This is the first study of its kind from this region where an effort has been
      made to put the cancer profile in East Rajasthan in perspective. A total of 2509
      histologically proven cancer cases were recorded from the various government and
      private hospitals in this region. There were 1443 males and 1066 females. Maximum
      number of cases were seen in the 6th and 5th decade. Genital tract cancer (21%)
      formed the largest overall group of cancers. When combined with the urinary
      system (7.6%)--the uro-genital tract cancers (28.7%) formed almost one-third of
      all cancers in this region. Cancer of the prostate (11.40%) and urinary bladder
      (9.1%) in males recorded the highest incidence in the country. Cancer of the
      female breast (19.4%) surpassed cancer cervix (18.2%). The frequency of penile,
      testicular, bone, skin, anorectal cancers and lymphoma was on the higher side.
      Whereas the incidence of stomach, oesophagus and lung cancer was on the lower
      side. An urgent need is felt to study the various aetiological factors
      responsible for these significant variations in Eastern Rajasthan.

PMID- 8557295
TI  - Solitary intracranial plasmacytoma of the skull base.
AB  - Two cases of extradural solitary plasmacytoma (SIP) with infiltration of the
      dura, destruction of the skull base, multiple cranial nerve palsies and proptosis
      are presented. The cases were treated aggressively with surgery and radiotherapy
      and showed no signs of progressing to multiple myeloma after 15 months and four
      and a half years respectively.

PMID- 8557296
TI  - Systemic fungal infections: major problems in cancer patients.
AB  - Over the last decade, with increasing use of aggressive chemotherapy and bone
      marrow transplantation in the treatment of cancer, fungi have emerged as a major
      pathogen. The prognosis of established systemic fungal infections remains poor,
      but newer antifungal drugs such as fluconazole are changing the outlook of
      therapy and prophylaxis considerably.

PMID- 8557297
TI  - Cytohistomorphology of prostatic lesions--by FNAC & scrape methods.
AB  - A pilot study of transrectal fine needle aspiration biopsy was conducted in 44
      patients, above the age of 50 years, who presented with features of obstructive
      uropathy during a one year period between August 1990 and April 1991.
      Histopathological study was carried out in 23 out of 44 patients, who underwent
      total prostatectomy or transurethral resection following the aspiration biopsy
      procedure. In 21 patients FNAB by the transrectal route could not be obtained
      because of technical difficulties; therefore intraoperative scrape cytology was
      studied prior to histopathology, of the fresh prostatic specimen. A good
      cytohistopathological correlation was obtained by both methods; an accuracy of
      95.6% and 95.2% with FNAC and scrape respectively. A wide range of benign and
      malignant lesions were studied.

PMID- 8557298
TI  - Plasma selenium level in cancer patients.
AB  - Selenium has been shown to be a cancer preventive agent. A few studies have shown
      that increased selenium level is associated with decreased cancer incidence and
      decreased cancer mortality. The present study was carried out to find out the
      relationship of selenium level with site, extent of disease, recurrence of
      disease, histopathological diagnosis, anaemia and serum protein level of cancer
      patients. Plasma selenium level were studied in 100 patients and mean selenium
      level of 75.35 ng/ml in cancer patients was significantly less than control
      values (116.99 ng/ml) in normal healthy individuals (P < 0.003). The strongest
      association of plasma selenium level and cancer was found in cancer breast (70.50
      ng/ml) and gastrointestinal tract (73.05 ng/ml) cancer. Selenium level decreased
      with the progress of disease and recurrence of disease. No significant
      association between histopathological diagnosis and selenium level was observed.
      Anaemia and hypoproteinemia was also not found to be related with selenium level.

PMID- 8557299
TI  - Intraventricular neurocytoma: a report of two cases.
AB  - Central neurocytomas are uncommon intracranial neoplasms. More than one hundred
      cases are documentated in the literature. In this report we describe the clinical
      and histopathological features in two patients with intraventricular neurocytoma.
      As the light microscopic features of neurocytoma resemble with that of an
      oligodendroglioma, it is essential to differentiate these two tumours, using
      either ultrastructural or immunohistochemical techniques.

PMID- 8557300
TI  - Composite carcinoid carcinoma of the colon--a case report.
AB  - A composite tumour of the caecum and colon, comprising of distinct areas of
      classical carcinoid and of well differentiated adenocarcinoma is described. Both
      components were histochemically confirmed. Presence of a morphologic transition
      at junctional areas favour a histogenesis from bi-directional differentiation of
      multipotent precursor cells.

PMID- 8557301
TI  - The neurotropic variant of desmoplastic spindle cell melanoma of the foot--a
      report of two cases with special reference to its schwanian features.
AB  - Melanomas are known to show a wide range of morphological expression.
      Desmoplastic Malignant Melanoma (DMM) which is a variant of spindle cell
      melanoma, is often characterised by conspicuous growth in and around nerves which
      leads to a mistaken diagnosis of malignant Peripheral Nerve Sheath tumours
      (MPNST). We report two such cases of spindle celled DMM of the foot which
      displayed neurotropism. The problems and the clinical relevance of distinguishing
      this variant of melanoma from MPNST is discussed.

PMID- 8557302
TI  - Omento-mesentral myxoid hamartoma--a case report.
AB  - Omento-mesentral myxoid hamartoma, a very rare lesion seen in children, is
      reported in a three year old child. Its rarity, problem in its clinical pre
      operative diagnosis, its characteristic gross and microscopic features, its
      benign, non recurrent clinical course is stressed.

PMID- 8557303
TI  - Joint annual meeting of the Austrian Society for Allergy and Immunology and the
      Society for Immunology. Vienna, September 27-30, 1995. Abstracts.

PMID- 8557304
TI  - The pineal gland: structural and functional diversity.
AB  - The article reviews the work carried out on pineal structure and function in
      vertebrates. The pineal has undergone striking changes in structure during the
      course of evolution from lamprey to mammals. In the primitive vertebrates,
      structure of the pineal is very much similar to that of the retina of the eyes
      and it acts as a direct photosensory organ. It acts as a photosensory and
      secretory organ in a number of species. Interestingly, the pineal complex among
      the reptiles presents the full spectrum of its morphological possibilities. There
      is a gradual regression of light sensitive pineal structure during the course of
      avian line of evolution. Further, it has been unequivocally accepted that
      mammalian pineal is an endocrine organ. The pineal is a prominent secretory
      organ, in mammals, which synthesises and secretes a number of exocrine and
      endocrine substances, such as indoles, peptides, various enzymes, amino acids and
      their derivatives, lipids, carbohydrates, and inorganic constituents. Pineal
      plays an important role in regulation of seasonal breeding in various vertebrate
      species. It is also considered as one of the most important components of the
      vertebrate circadian system and is a principal source of rhythmically produced
      melatonin. Apart from the above mentioned functions, pineal also influences
      thermoregulation, electrolyte metabolism, intermediary metabolism, hemopoiesis,
      immune system and behaviour.

PMID- 8557305
TI  - Inversion polymorphism in Drosophila ananassae: persistence of inversions,
      heterosis and intra- and inter-chromosomal associations in experimental
      populations of mixed geographic origin.
AB  - Two experimental populations of D. ananassae were synthesised by making
      reciprocal crosses among five geographic strains and mixing the hybrids. Each of
      the two populations of mixed geographic origin was maintained as mass cultures in
      food bottles. After five generations chromosomal analysis of these two
      populations was made by squashing a large number of larvae. The results showed
      that both experimental populations remained polymorphic due to the persistence of
      AL, (2L), ZE (2R) and DE (3L) inversions in population A and AL, ZE, DE and ET
      (3R) inversions in population B. Persistence of inversions in considerable
      frequency and significant deviation from Hardy-Weinberg equilibrium showed that
      heterosis is associated with these four inversions in D. ananassae. Further,
      there is non-random association (linkage disequilibrium) between linked
      inversions in second (AL-ZE) chromosome. However, the inversions of the different
      chromosomes are associated randomly indicating no interchromosomal interactions
      in D. ananassae. The results of these studies on population dynamics of inversion
      polymorphism in experimental populations are attributable to selection, genetic
      drift and Founder effect.

PMID- 8557306
TI  - Efficiency of routine semen analysis to predict functional and structural
      integrity of human spermatozoa.
AB  - The study is to examine the ability of routine semen analysis to predict the
      functional and structural integrity of spermatozoa in in vitro conditions. Since
      large number of subjects were evaluated over a long period of time, the value of
      routine analysis to prognosticate the functional and structural integrity in the
      same sample was assessed. Routine semen analysis was done on 354 subjects. In the
      same sample, functional tests were carried out. The functional tests applied were
      hypoosmotic swelling test, test for acrosome intactness, nuclear chromatin
      decondensation test and sperm mitochondrial activity index. A scoring system was
      adopted for both routine and functional analysis. According to the scores
      obtained, the samples were categorized into fertile, subfertile and infertile.
      Analysis of the data indicated that efficiency of routine semen analysis was
      38.13%. Prediction of functional integrity by routine analysis of semen specially
      in subnormal cases is only partly fulfilled. The study also indicates that
      functional tests are definitely indicated in cases with subnormal score.

PMID- 8557307
TI  - Effect of adrenalectomy and adrenalectomy+hydrocortisone treatment on
      histopathological, biochemical and zinc and copper profiles in rat testes.
AB  - Degenerative changes such as decreased seminiferous tubule diameter, Leydig cell
      nuclear diameter, spermatogenic arrest, oedematous fluid in the interstitium and
      lumen of seminiferous tubules and increased levels of zinc, copper and enzymes
      (lactate dehydrogenase, LDH; leucine aminopeptidase, LAP; and aryl sulphatase) in
      adrenalectomised rats suggest a possible role of adrenal cortex and its hormones
      in spermatogonial cell proliferation and subsequent differentiation, homeostasis
      of biological trace elements and behaviour of enzymes. Atrophy of Leydig cells
      and the degenerative changes in testes of adrenalectomised rats can be attributed
      to reduced supply of testosterone. Hydrocortisone, administered through a single
      dose acted as hyperstate of hydrocortisone for a short duration, thereby
      inhibiting steroidogenesis either directly by affecting Leydig cell testosterone
      production or indirectly by affecting the release of LH from pituitary gland and
      thus caused degeneration of germinal epithelium. Once hydrocortisone (half life <
      12 hr) was metabolized, the animals returned to adrenalectomised state, the
      degeneration persisted. Thus, hydrocortisone administered through a single dose
      was insufficient to sustain spermatogenesis. Chronic administration at
      physiological dose may renew spermatogenesis. Increased levels of LDH, LAP and
      arylsulphatase are, probably, necessary for cellular degeneration. Zinc and
      copper exhibited an increase and the rise can be corroborated to (1) failure of
      regulatory mechanism(s) that control the flow of the elements across the blood
      testes barrier; and (2) increased oedematous fluid formed by cellular deaths of
      the germinal epithelium.

PMID- 8557308
TI  - Effect of long-term administration of melatonin on eyes and harderian glands in
      albino rat.
AB  - Pineal hormone melatonin is also synthesized by the ocular structures, retina and
      Harderian gland. The physiological significance of such production is not fully
      understood. Daily treatment with melatonin (25 micrograms/rat) for 8 weeks led to
      an increase in weight of eye balls and fluid within it (P < 0.05). Weight of the
      Harderian gland in the control and treated rats was not significantly different,
      though the histological observation revealed an increase in cell height and
      reduction in lumen diameter in the treated animals. Inter luminal deposits of
      porphyrin content appeared to be more in the Harderian glands of melatonin
      treated rats. The retinal tissue indicated degenerative changes in the melatonin
      treated rats. The results suggest melatonin's influence on level of ocular fluid,
      structure/function of retina and harderian gland.

PMID- 8557309
TI  - Quantitative and qualitative analysis of accessory gland secretory proteins in a
      few species of Drosophila immigrans group.
AB  - Quantitative and qualitative analysis of accessory gland proteins in four species
      of D. immigrans group has been made. Quantitative estimation of these proteins
      during development of the adult male revealed that there is a gradual increase in
      the quantity of secretions up to 7 days. The secretions constitute 72, 70, 50 and
      54.2% in D.n. nasuta, D.s. neonasuta, D. rubida and D. pararubida respectively.
      Mating experiments showed that more than 1/3 of this stored secretory protein is
      transferred into the female reproductive tract during first mating. SDS-PAGE
      analysis of the accessory gland secretions revealed remarkable simplicity in
      their patterns, including the absence of age dependent alterations. In all the 4
      species analysed, only the low mol. wt. fractions are not glycosylated. It was
      further observed that the extent of similarity between D.n. nasuta and D.s.
      neonasuta is greater than between D. rubida and D. pararubida.

PMID- 8557310
TI  - Investigations on wound healing by using amphibian skin.
AB  - The present investigation is aimed to justify the validity of traditional
      practice of using the frog skin in wound healing. Studies were carried out on
      skin wounds from female albino rats of Wistar strain weighing 100-120 g. The
      wounds of standard size (5 cm2) were created in the experimental and control
      groups. The experimental group was dressed with dorsal skin of freshly sacrificed
      frogs (Rana tigrina) while the control group was dressed with cotton gauze. A
      faster healing was observed in the experimental group over the control group.
      Biochemical estimations of the wound granulation tissue were carried out every 2
      days till the complete healing of the wound in both the groups. The collagen of
      frog skin was extracted and polyacrylamide gel electrophoresis was carried out to
      characterize and identity the molecular organization of collagen type.

PMID- 8557311
TI  - Role of prostaglandin synthesis inhibitors on chemically induced seizures.
AB  - The study was conducted to find out the possible role of prostaglandin synthesis
      inhibitors on different parameters of chemically induced seizures in albino mice.
      The results suggest that prostaglandins have a proconvulsant activity.
      Augmentation of central dopamine and serotonin levels is partly responsible for
      the inhibitory effect of prostaglandin synthesis inhibitors on chemically induced
      seizures.

PMID- 8557312
TI  - Assessment of endocrine response of Inula racemosa in relation to glucose
      homeostasis in rats.
AB  - Alcoholic extract of the root of I. racemosa lowers blood glucose and enhances
      liver glycogen without increasing plasma insulin in rats. There is also no
      increase in degree of degranulation of the beta cells of pancreas. In similar
      conditions it does not show any effect on activity of adrenal gland. However,
      thyroid gland undergoes activation at the later stage (delayed response). It
      appears that hypoglycemic response of I. racemosa is not due to enhanced
      secretion/synthesis of insulin; the action may be at the peripheral level by
      potentiating the insulin sensitivity.

PMID- 8557313
TI  - Extracellular production of alpha-rhamnosidase by Rhizopus nigricans.
AB  - Extracellular production of alpha-rhamnosidase [EC 3.2.1.40] from an indigeneous
      fungal strain of R. nigricans has been demonstrated. The enzyme has been shown to
      follow Michaelis-Menten kinetics using p-nitrophenyl-alpha-L-rhamnopyranosid as a
      substrate. The pH and the temperature optima of the enzyme have been found to be
      around 6.5 and 60 degrees-80 degrees C respectively.

PMID- 8557314
TI  - Expression of porcine transforming growth factor-beta.
AB  - Altered porcine transforming growth factor-beta (TGF-B)-cDNA was ligated to the
      expression vector. The resultant plasmid, pSA10041 was cotransfected with pSV2neo
      plasmid in NIH3T3 cells and clones were selected using G418. The clones were
      checked for integration of TGF-B-cDNA by PCR. The western blotting results
      confirm the expression of TGF-B in NIH3T3 cells. This construct can be used to
      develop transgenic mice to study its effect in vivo.

PMID- 8557315
TI  - Protein phosphatase-1 inhibition induces high SCEs in normal whole blood
      cultures.
AB  - Effect of 1,25,50 and 75 nM of okadaic acid (OA) on human lymphocytes from
      healthy individuals in culture has been investigated. To our surprise, we
      observed induction of significantly high sister chromatid exchanges (SCEs) at
      concentrations known to inhibit both protein phosphatase-1 (PP-1) and protein
      phosphatase -2A (PP-2A). However, 1 nM okadaic acid, known to inhibit PP-2A
      alone, did not induce this cellular feature/phenotype. This novel preliminary
      observation lays foundation for investigating further the role of PP-1 inhibition
      in governing as yet unknown finer controls in the induction of high SCEs, the
      mechanism for which has eluded answers till date.

PMID- 8557316
TI  - Determination of high level resistance to aminoglycosides among enterococci.
AB  - Two hundred and ten strains of enterococci showing resistance to gentamicin (10
      micrograms/disc) were tested for high level resistance by detecting the minimum
      inhibitory concentration and by using high content disc diffusion test. Only 67
      per cent of these had high level resistance to gentamicin. High level kanamycin
      resistance in the group was 84 per cent, while high level streptomycin resistance
      was 61 per cent. Only 85 of the 140 strains with high level gentamicin resistance
      had similar streptomycin resistance. Results using locally made high content
      discs, correlated 100 per cent with MIC results. High level resistance to
      enterococci should be reported on a routine basis, especially when isolated from
      patients with serious infections.

PMID- 8557317
TI  - C substance--specific latex agglutination for early & rapid detection of
      Streptococcus pneumoniae in blood cultures.
AB  - A slide agglutination test was developed using latex particles coated with
      antiserum against the C substance, a common antigen for all serotypes of
      Streptococcus pneumoniae. This test was used for the rapid identification of
      pneumococci in blood culture broths which contained Gram positive cocci (GPC) in
      pairs or short chains on smear examination. Of 238 consecutive blood cultures
      with GPC tested, 72 were positive for Strep. pneumoniae by the latex test and
      conventional methods. The remaining 166 cultures were negative for both these,
      indicating a 100 per cent specificity and sensitivity for the test.

PMID- 8557318
TI  - Antimicrobial susceptibility pattern & biotyping of Helicobacter pylori isolates
      from patients with peptic ulcer diseases.
AB  - Antimicrobial susceptibility of 50 local isolates of Helicobacter pylori from
      patients with acid peptic diseases was investigated to commonly used antibiotics.
      The maximum resistance was (66%) detected to metronidazole (MIC > 8
      micrograms/ml). The frequency of resistance to ampicillin, erythromycin,
      ciprofloxacin was in the range of 20-28 per cent; least resistance was observed
      to tetracycline (10%). The gradient disc diffusion method was found to give
      reproducible results and also correlated with agar dilution method for minimum
      inhibitory concentration (MIC). Study of the enzymatic activity of H. pylori
      isolates showed that all isolates had urease, catalase, oxidase, esterase-lipase,
      and naphthol-AS-beta-1-phosphohydrolase enzymes and were consistently negative
      for ten other enzymes tested. Majority of the isolates expressed alkaline
      phosphatase (17/18), esterase (17/18) and acid phosphatase (14/18). The acid
      phosphatase had the maximum mean enzymatic activity. There was no difference in
      enzymatic activity between H. pylori isolates from ulcer and gastritis patients.
      H. pylori isolates could be typed into five biotypes. Type III was found to be
      more common (44.4%). This study supports the existence of the strain variations
      among H. pylori on the basis of the enzyme profiles.

PMID- 8557319
TI  - Evaluation of effectiveness of mouse brain inactivated Japanese encephalitis
      vaccine produced in India.
AB  - Efficacy of mouse brain inactivated Japanese encephalitis vaccine was evaluated
      by studying the immune status of volunteers 1,2,3,4.5 and 7.5 yr after
      immunization. Neutralizing (N) antibody which is protective and found to
      correlate with the immunity after vaccination was estimated in serum by plaque
      reduction neutralizing test on chick embryo cell monolayer. Mean N-antibody
      titres of 3.25 (pre-booster) and 3.6, 2.8, 2.06, 1.85 and 1.50 log10 were
      observed post-booster, and 1,2,3, and 4.5 yr of immunization in volunteers who
      received complete immunization (3 doses). All the volunteers retained more than
      1.0 log10 titre of protective N-antibody in spite of the loss of 0.8, 0.74, 0.21
      and 0.35 log10 after 1,2,3, and 4.5 yr respectively. Similarly mean N-antibody
      titres of 1.6, 3.25, 2.4, 2.25, 1.92 and 1.60 log10 were observed pre-booster,
      after a single booster dose, and 1,2,3 and 4.5 yr of vaccination in individuals
      who received only a single booster dose. Ten serum samples of volunteers tested
      after 7.5 yr of vaccination showed that those who were in constant contact with
      JE virus (n = 7) in the laboratory maintained high levels of N-antibody whereas
      others (n = 3) showed a fall in titre indicating the necessity of a booster dose.

PMID- 8557320
TI  - Sudden spurt of cryptococcosis at a tertiary care hospital at New Delhi between
      December 1994 to February 1995.
AB  - In a short span of three months, nine patients of cryptococcal infection were
      diagnosed at the All India Institute of Medical Sciences (AIIMS), New Delhi with
      varied clinical presentation. Predisposing factors could be ascertained in two
      patients only. The diagnosis was based on the direct demonstration of the
      organism followed by successful culture supported by histopathology (in one
      patient) and radiology. The specific antigen was also detected in the body
      fluids. The increased awareness and greater suspicion helped in the diagnosis of
      these patients. Those who were diagnosed early, responded well with specific
      antifungal therapy.

PMID- 8557321
TI  - Effect of intrauterine growth retardation on postnatal changes in body
      composition of preterm infants.
AB  - To find the effect of intrauterine growth retardation on postnatal changes in
      body composition, we studied nine preterm small for date (SFD) and 9 gestation
      matched appropriate for gestational age (AGA) infants (mean +/- SD birth weight -
      SFD : 1431 +/- 16I g, AGA : 1904 +/- 223 g, gestational age - SFD; 237 +/- 9
      days, AGA : 236 +/- 7 days). Total body water (TBW) and extracellular water (ECW)
      were measured at birth, on the day of maximum weight loss and on regaining of
      birth weight. Body solids were calculated from the difference between TBW and
      body weight. SFD infants had significantly less postnatal weight loss (64 +/- 19
      g) than AGA infants (135 +/- 49 g; P < 0.01) and showed a significant gain in
      body solids (19 +/- 12 g) during this period which was not seen in AGA infants (
      4 +/- 14 g; P < 0.05). The subsequent weight gain occurred at similar rates in
      SFD (16 +/- 4 g/day) and AGA (18 +/- 6 g/day) infants, but a significantly higher
      ratio of the weight gain consisted of solids in SFD as compared to AGA infants (P
      < 0.05). Per unit of body weight, SFD infants had significantly less body solids
      (213 +/- 12 g/kg) than AGA infants (228 +/- 18 g/kg; P < 0.05) at birth, but by
      the time birth weight was regained the two groups of infants had similar probody
      solids (SFD: 248 +/- 7 g/kg, AGA : 255 +/- 12 g/kg). These results suggest that
      in SFD infants catch-up growth starts early, during the period of apparent weight
      loss.

PMID- 8557322
TI  - Defective lymphoproliferative responses & interleukin-2 production in chronic
      renal failure patients.
AB  - Cellular immune responses were evaluated in 12 early renal failure (ERF) patients
      who were not on maintenance haemodialysis, 43 end stage renal disease (ESRD)
      patients on haemodialysis (HD) and 25 healthy volunteers. Peripheral blood
      mononuclear cells (PBMC) of ERF and ESRD patients on HD had a significantly
      diminished lymphoproliferative responses to phytohaemagglutinin and a monoclonal
      antibody to the CD3 (anti-CD3) receptor on T-cells as compared to normals. The
      interleukin-2 (IL-2) production by the PBMC was also significantly reduced in
      renal failure patients as compared to normals. These data suggest that both IL-2
      dependent and IL-2 independent T-cell functions are defective in renal failure
      patients.

PMID- 8557323
TI  - The pulmonary toxicity of cinnamon dust in rats.
AB  - The histopathological effect of a single intratracheal dose of respirable
      cinnamon dust, cinnamon dust extract, and cellulose dust on the lungs of rats was
      studied sequentially one, seven days and one month after treatment. Exposure to
      respirable cinnamon and cellulose dusts resulted in alveobronchiolitis at the end
      of the first and seventh day, and fibrotic changes by the end of the first month.
      As the extract of cinnamon dust caused no histopathological alterations, it is
      assumed that the cellulose content of cinnamon dust was responsible for the
      histological reactions.

PMID- 8557324
TI  - Comparison of immune responses of mice immunized with five different
      Mycobacterium bovis BCG vaccine strains.
AB  - Among the various parameters which may contribute to Mycobacterium bovis BCG
      vaccination efficiency, the choice of the vaccine strain may play an important
      role. In the present study, we therefore compared the immunogenicity of five
      different BCG strains that are commonly used for BCG vaccine production (Glaxo
      1077, Japanese 172, Pasteur 1173P2, Prague, and Russian strains). The comparison
      of the growth capacity of these BCG strains in BALB/c and C3H mice demonstrated
      that a great difference exists between the capacity of various BCG strains to
      multiply and persist in target organs. A much lower recovery of BCG could be
      shown in mice immunized with Prague and Japanese BCG strains. T-cell responses of
      BCG-immunized mice were also examined by analyzing T-cell proliferative
      responses, cytokine production, delayed-type hypersensitivity responses, and
      cytotoxic activity. All these assays demonstrated that BCG immunization induced
      strong CD4+ T-cell responses, mostly of the Th1 type, as demonstrated by
      interleukin-2 and gamma interferon production. These studies also demonstrated
      that there are differences between BCG strains in stimulating these T-cell
      responses. A lack of induction of cytotoxic activity was observed following
      immunization with the Japanese strain. Lower anti-purified protein derivative
      antibody responses were also observed after intravenous or oral immunization with
      this BCG strain. Finally, the protective activity of these BCG strains was tested
      by measuring the capacity of immunized mice to eliminate recombinant Pasteur and
      Japanese BCG strains which expressed beta-galactosidase. The results of these
      experiments clearly demonstrated that the Prague and Japanese strains were unable
      to protect mice against a second mycobacterial challenge whereas mice immunized
      with the Glaxo, Pasteur, or Russian strain eliminated the recombinant BCG very
      efficiently. Altogether, the results of the present study strongly support the
      view that there are considerable differences in the immunogenicity of various BCG
      vaccine strains and that these differences may play a major role in BCG
      vaccination efficiency.

PMID- 8557325
TI  - Factors influencing secondary vibriocidal immune responses: relevance for
      understanding immunity to cholera.
AB  - Although serum vibriocidal activity is used extensively as a marker of immunity
      to O1 Vibrio cholerae, there are limitations in this assay to detect instances of
      reexposure. We define the conditions operative in producing secondary vibriocidal
      responses in North American volunteers primed with either wild-type V. cholerae
      1, 4, or 6 months later. Secondary serum vibriocidal responses occurred under two
      distinct secondary challenge conditions. The first occurred when secondary
      challenge produced a breakthrough in clinical protection. Following secondary
      exposure, 14 of 22 (64%) and 1 of 29 (3%) subjects with and without vibrio stool
      excretion, respectively, had secondary responses (P < 0.001); 5 of 6 (83%) and 10
      of 45 (22%) subjects with or without diarrhea, respectively, mounted a secondary
      response (P = 0.006). The second condition occurred in the presence of full
      clinical protection but was dependent on the time interval between exposure. No
      subject (0 to 17) vaccinated with CVD 103-HgR and given homologous wild-type
      challenge within 4 months mounted a secondary vibriocidal response (P = 0.0009).
      The majority of the serum vibriocidal activity was of the immunoglobulin M (IgM)
      isotype, seen in 96 and 73% of subjects following primary and secondary exposure,
      respectively. Vibriocidal activity in the IgG fraction following primary and
      secondary exposures occurred with < or = 50% of volunteers; lipopolysaccharide
      (LPS)-specific IgG1 and IgG3 subclass responses supported the vibriocidal isotype
      data. However, following primary exposure, IgG4 LPS responses predominated,
      occurring in 81% of responding volunteers. These data suggest that, under certain
      conditions of secondary exposure to V. cholerae O1 antigens, when there is
      sufficient active local immunity present, there is a block of vibrio antigen
      resampling at the M cell level. We discuss the implications of and possible
      explanations for these findings.

PMID- 8557326
TI  - Molecular characterization, occurrence, and immunogenicity in infected sheep and
      cattle of two minor outer membrane proteins of Brucella abortus.
AB  - Screening of a Brucella abortus genomic library with two sets of monoclonal
      antibodies allowed the isolation of the genes corresponding to two minor outer
      membrane proteins (OMP10 and OMP19) found in this bacterial species. Sequence
      analysis of the omp10 gene revealed an open reading frame capable of encoding a
      protein of 126 amino acids. The nucleotide sequence of the insert producing the
      OMP19 protein contains two overlapping open reading frames, the largest of which
      (177 codons) was shown to encode the protein of interest. Analysis of the N
      terminal sequences of both putative proteins revealed features of a bacterial
      signal peptide, and homology to the bacterial lipoprotein processing sequence was
      also observed. Immunoblotting with monoclonal antibodies specific for OMP10 or
      OMP19 showed that both proteins are present in the 34 Brucella strains tested,
      representing all six Brucella species and all their biovars. The OMP19 detected
      in the five Brucella ovis strains examined migrated at an apparent molecular
      weight that is slightly higher than those of the other Brucella species,
      confirming the divergence of B. ovis from these species. OMP10 and OMP19 were
      produced in recombinant Escherichia coli and purified to homogeneity for
      serological analysis. A large fraction of sera from sheep naturally infected with
      Brucella melitensis were reactive with these proteins in an enzyme-linked
      immunosorbent assay, whereas sera from B. abortus-infected cattle were almost
      completely unreactive in this assay.

PMID- 8557327
TI  - Endotoxin-induced enhancement of glucose influx into murine peritoneal
      macrophages via GLUT1.
AB  - Hypoglycemia is among the most injurious metabolic disorders caused by
      endotoxemia. In experimental endotoxemia with lipopolysaccharide (LPS) in
      animals, a marked glucose consumption is observed in macrophage-rich organs.
      However, the direct effect of LPS on the uptake of glucose by macrophages has not
      been fully understood, and the present study was undertaken to shed light on this
      point. The consumption and uptake of glucose, as measured with 2-deoxy-D
      [3H]glucose, by murine peritoneal exudate macrophages in culture were accelerated
      two- to threefold by stimulation with 3 ng of LPS per ml. The rate of glucose
      uptake reached a plateau after 20 min of stimulation and remained at the maximum
      as long as LPS was present. Northern (RNA) blot analysis with cDNA probes for
      five known isoforms of glucose transporter (GLUT) revealed that the expression of
      GLUT by macrophages was restricted to the GLUT1 isoform during LPS stimulation
      and the amount of GLUT1 mRNA was increased by the stimulation. These results
      suggest that macrophage responses to LPS are supported by a rapid and sustained
      glucose influx via GLUT1 and that this is a participating factor in the
      development of systemic hypoglycemia when endotoxemia is prolonged.

PMID- 8557328
TI  - Bacteroides fragilis enterotoxin induces cytoskeletal changes and surface
      blebbing in HT-29 cells.
AB  - Certain strains of the anaerobic bacterium Bacteroides fragilis are known to
      produce an enterotoxin of about 20 kDa which is able to induce a fluid response
      in ligated intestinal loops and a cytotoxic response in HT-29 cells. It presents
      protease activity, belonging to a family of metalloproteases termed metzincins.
      In order to investigate the mode of action of the enterotoxin in cultured cells,
      we performed a study with HT-29 cells, using both fluoresence and electron
      microscopy. Treated cells underwent morphological changes, mainly consisting of
      the retraction of the cell body and the formation of numerous blebs on the cell
      surface. The microfilament system was reorganized, the F-actin being condensed as
      a ring at the cell periphery, whereas other cell organelles appeared to be
      unaffected. All these changes, clearly visible after 3 h of exposure to the
      toxin, were reversed within 24 h of treatment. By inhibiting the protease
      activity of the toxin with specific metal chelators, the cytoskeletal effects
      were also prevented. Thus, B. fragilis enterotoxin appears to act on cells by
      reversibly modifying the actin cytoskeleton, an effect probably dependent on its
      proteolytic activity.

PMID- 8557329
TI  - A patient-derived cytotoxic T-lymphocyte clone and two peptide-dependent
      monoclonal antibodies recognize HLA-B27-peptide complexes with low stringency for
      peptide sequences.
AB  - HLA-B27 molecules expressed on the T2 mutant cell line do not have peptides. Such
      empty HLA-B27 molecules were not recognized by an HLA-B27-restricted cytotoxic T
      lymphocyte (CTL) clone (auto-1) derived from synovial fluid. To test for peptide
      dependency of the clone, B27-T2 cells were incubated with a panel of 48 different
      peptides. This lack of stringency was compared with that of a peptide-dependent
      monoclonal antibody, B27.M2. Positive B27.M2 reactivity resulted when the B27-T2
      cells were incubated with two peptides: RRKAMFEDI and RRMGPPVGHR, derived from
      Chlamydia HSP60 and human ribonucleoprotein, respectively. Because of the limited
      availability of CTL versus monoclonal antibody, the specificity of B27.M2 was
      studied in greater detail. The importance of the HLA-B27 heavy chain in antibody
      recognition of class I-peptide complexes was demonstrated by site-directed
      mutagenesis. The stringency of the peptide residues was tested by making analogs
      of each of the nine residues in RRKAMFEDI, creating a panel of 180 analogs.
      Although stringency was highest for the sixth position, as many as six different
      amino acids provided positive reactivity. These results indicate that immune
      recognition of HLA-B27-peptide complexes might have rather low stringency for the
      peptide sequences. In theory, then, pathogen-derived peptides which induce
      autoimmunity by generating autoreactive CTL might not share much sequence
      similarity with the responsible self peptides.

PMID- 8557330
TI  - Regulation of Trypanosoma cruzi infection in mice by gamma interferon and
      interleukin 10: role of NK cells.
AB  - Gamma interferon (IFN-gamma) plays an important role in experimental Trypanosoma
      cruzi infections, presumably by controlling the early replication of parasites in
      host macrophages. In this work, we show that NK cells represent an important cell
      type responsible for the production of most of the IFN-gamma in the early stage
      of T. cruzi infection and that the in vivo treatment of mice with anti-NK1.1
      monoclonal antibody made resistant animals susceptible to the infection. Through
      in vitro experiments, we demonstrate that normal splenocytes from euthymic or
      athymic nude mice cultivated for 48 h with live T. cruzi trypomastigotes produced
      elevated levels of IFN-gamma. In addition, NK-depleted splenocytes show a drastic
      reduction of IFN-gamma production in response to live T. cruzi trypomastigotes.
      We also demonstrated that IFN-gamma production is dependent on a factor secreted
      by adherent cells. Supernatants of spleen cells from athymic nude mice are able
      to induce IFN-gamma production by normal splenocytes when cultured with
      trypomastigotes. The addition of anti-interleukin-10 to these cultures resulted
      in a marked increase in IFN-gamma production. On the other hand, the absence of
      NK cells led to an increased secretion of interleukin-10 upon in vitro
      stimulation with T. cruzi. Taken together, these results suggest that NK cells
      are the major source of IFN-gamma that could be involved in limiting the
      replication of T. cruzi in host macrophages during the early acute phase of the
      infection.

PMID- 8557331
TI  - Adherence of Salmonella typhimurium to Caco-2 cells: identification of a
      glycoconjugate receptor.
AB  - The mechanism by which Salmonella species adhere to the epithelium of the
      intestine is not well understood. To identify components on intestinal epithelial
      cells that may be involved in the initial adherence of Salmonella typhimurium, we
      correlated patterns of adherence to well-differentiated Caco-2BBe cell monolayers
      with expression of brush border membrane components and lectin binding sites.
      This cloned cell line shows heterogeneous expression of sucrase-isomaltase and
      most lectin receptors. S. typhimurium adhered to a subpopulation of living or
      formaldehyde-fixed cells with a high multiplicity (up to 150 bacteria per cell).
      Bacterial binding to selected cells was not correlated with expression of the
      brush border hydrolases dipeptidyl-peptidase IV and sucrase-isomaltase or with
      binding of 10 of the 12 lectins tested. However, binding was correlated with the
      presence of binding sites for peanut agglutinin (PNA) [specific for Gal beta (1
      3) GalNAc] and soybean agglutinin (specific for terminal GalNAc). Preincubation
      of live and fixed Caco-2BBe monolayers with PNA inhibited bacterial binding,
      while preincubation with soybean agglutinin did not. Electron microscopic
      analysis demonstrated that the initial adherence of S. typhimurium to Caco-2
      cells in vitro involved peripheral components of the glycocalyx on apical
      microvilli. These results suggest that a Gal beta (1-3)GalNAc epitope recognized
      by PNA and located in the glycocalyx is involved in the early recognition events
      between S. typhimurium and Caco-2 cells and that differences in glycosylation
      patterns among individual epithelial cells may be a determinant in cell-selective
      adherence of S. typhimurium.

PMID- 8557332
TI  - Outer membrane protein A of Escherichia coli contributes to invasion of brain
      microvascular endothelial cells.
AB  - Escherichia coli is the most common gram-negative bacteria causing meningitis
      during the neonatal period, but is unclear what microbial factors mediate
      traversal of E. coli across the blood-brain barrier. Outer membrane protein A
      (OmpA), a highly conserved 35-kDa protein, was examined for its role in E. coli
      K1 invasion of brain microvascular endothelial cells (BMEC). The invasive
      capability of the OmpA+ strains was 25- to 50-fold greater than that of OmpA-
      strains, and the invasive capability of OmpA- strains was restored to the level
      of the OmpA+ strain by complementation with the OmpA+ E. coli into BMEC. Two
      short synthetic peptides (a hexamer, Asn-27-Glu-32, and a pentamer, Gly-65-Asn
      69) generated from the N-terminal amino acid sequence of OmpA exhibited
      significant inhibition of OmpA+ E. coli invasion, suggesting that these two
      sequences represent the OmpA domains involved in E. coli invasion of BMEC. These
      findings suggest that OmpA is the first microbial structure identified to enhance
      E. coli invasion of BMEC, an important event in the pathogenesis of E. coli
      meningitis.

PMID- 8557333
TI  - Endothelial cell GlcNAc beta 1-4GlcNAc epitopes for outer membrane protein A
      enhance traversal of Escherichia coli across the blood-brain barrier.
AB  - Inadequate knowledge of pathogenesis and pathophysiology has contributed to the
      high mortality and morbidity associated with neonatal Escherichia coli
      meningitis. We have shown previously that outer membrane protein A (OmpA)
      contributes to E. coli K1 membrane invasion of brain microvascular endothelial
      cells. In this study we report that this OmpA+ K1 E. coli invasion of brain
      microvascular endothelial cells was inhibited by wheat germ agglutinin and
      chitooligomers prepared from the polymer of 1,4-linked GlcNAc, chitin. The
      specificity of the interaction between OmpA and GlcNAc beta 1-4GlcNAc epitopes
      was verified by the demonstration that chitotriose-bound OmpA and wheat germ
      agglutinin-bound brain microvascular endothelial cell membrane proteins inhibit
      E. coli K1 invasion. Of interest, OmpA+ E. coli invasion into systemic
      endothelial cells did not occur, but invasion similar to that of brain
      microvascular endothelial cells was observed when systemic cells were treated
      with alpha-fucosidase, suggesting that the GlcNAc beta 1-4GlcNAc moieties might
      be substituted with L-fucose on these cells. More importantly, the chitooligomers
      prevented entry of E. coli K1 into the cerebrospinal fluid of newborn rats with
      experimental hematogenous E. coli meningitis, suggesting that the GlcNAc beta 1
      4GlcNAc epitope of brain microvascular endothelial cells indeed mediates the
      traversal of E. coli K1 across the blood-brain barrier. A novel strategy with the
      use of soluble receptor analog(s) may be feasible in the prevention of
      devastating neonatal E. coli meningitis.

PMID- 8557334
TI  - Evidence for occurrence of the ESAT-6 protein in Mycobacterium tuberculosis and
      virulent Mycobacterium bovis and for its absence in Mycobacterium bovis BCG.
AB  - ESAT-6 is a secreted protein present in the short-term culture filtrate of
      Mycobacterium tuberculosis after growth on a synthetic Sauton medium. ESAT-6 has
      recently been demonstrated to induce strong T-cell responses in a mouse model of
      memory immunity after infection with M. tuberculosis. In Western blotting
      (immunoblotting), the monoclonal antibody HYB76-8, reacting with ESAT-6, gave a 6
      kDa region was observed in filtrates from four of eight substrains of M. bovis
      BCG that produced high levels of MPB64, while no band occurred in the 6-kDa
      region with any of these BCG substrains. Southern blotting and PCR experiments
      with genomic mycobacterial DNA showed the presence of the esat-6 gene in
      reference strains and clinical isolates of M. tuberculosis as well as in virulent
      M. bovis. The esat-6 gene could not be demonstrated in any of the eight
      substrains of M. bovis BCG tested by these techniques. Two gene deletions that
      distinguish M. bovis BCG from virulent M. bovis have thus now been demonstrated.
      Deletion of mpb64 affects four of the eight substrains tested; deletion of esat-6
      affects all of them. The reaction of HYB76-8 AT 26 kDa with four of the BCG
      substrains was demonstrated to result from cross-reactivity with MPB64. HYB76-8
      was also shown to cross-react with the A, B, and C components of the antigen 85
      complex and MPT51.

PMID- 8557335
TI  - Multiple host defense defects in failure of C57BL/6 ep/ep (pale ear) mice to
      resolve visceral Leishmania donovani infection.
AB  - Euthymic C57BL/L ep/ep (pale ear [PE]) mice halt the visceral replication of
      intracellular Leishmania donovani but fail to properly resolve infection. A
      previous study identified an isolated defect in tissue granuloma formation in
      these mice; CD4+ and CD8+ cell number, gamma interferon (IFN-gamma) production,
      and macrophage antimicrobial activity in vitro were all intact. New in vivo
      results reported here suggest a considerably more complex immune defect, with
      evidence indicating (i) enhanced control over L. donovani after transfer of
      normal C57BL/6 spleen cells, (ii) a partially suppressive Th2 cell-associated
      response mediated by interleukin-4 (IL-4) but not reversed by CD4+ cell
      depletion, (iii) absent responses to endogenous Th1 cell lymphokines (IFN-gamma
      and IL-2) but preserved responsiveness to endogenous tumor necrosis factor alpha,
      (iv) absent responses to exogenous treatment with recognized antileishmanial
      cytokines (IFN-gamma, IL-2, IL-12, and granulocyte-macrophage colony-stimulating
      factor [GM-CSF]) not corrected by transfer of C57BL/6 spleen cells, and (v) a
      deficient response to antimony chemotherapy. Defective hepatic granuloma
      formation was not corrected by transfer of C57BL/6 spleen cells or by anti-IL-4
      administration. While treatment with IL-2 and GM-CSF modified the tissue reaction
      and induced selected effector cells to encase tissue macrophages, no
      antileishmanial activity resulted. Together, these observations suggest that the
      failure of PE mice to resolve visceral L. donovani infection likely represents
      expression of multiple suboptimal immune responses and/or partial defects,
      probably involving a combination of T-cell dysfunction, a Th2 cell response, and
      target cell (macrophage) hyporesponsiveness.

PMID- 8557336
TI  - Characterization of an RTX toxin from enterohemorrhagic Escherichia coli O157:H7.
AB  - A hemolytic determinant of enterohemorrhagic Escherichia coli O157:H7 is encoded
      on a 90-kbp plasmid (pO157). This enterohemorrhagic E. coli toxin (Ehx) is a
      newly described RTX cytotoxin. The prototype RTX toxin is the E. coli hemolysin
      (Hly) associated with extraintestinal E. coli infections. We expressed Ehx from
      E. coli K-12 strains harboring either pSK3, a pO157 derivative marked with Tn801
      unlinked to Ehx, or a recombinant plasmid containing an 11.9-kbp subclone (pEO40)
      of pSK3. The Ehx activities and antibody reactivities were compared with those of
      Hly. Little Ehx was secreted extracellularly from the strain harboring pSK3;
      however, when the Hly transport genes hlyBD were supplied in trans, both
      intracellular and extracellular levels of Ehx were enhanced more than 15-fold.
      The strain harboring pEO40 secreted at least 140-fold more Ehx than did the
      strain harboring pSK3, and neither intracellular nor extracellular levels were
      significantly enhanced by the addition of hlyBD in trans. Polyclonal anti-HlyA
      antiserum and several anti-HlyA monoclonal antibodies, including the monoclonal
      antibody A10, which is panreactive for nearly all RTX toxins, reacted with EhxA
      antigen by immunoblot analysis. In hemolysis and 51Cr release assays, Ehx
      demonstrated similar efficiencies in lysis of BL-3 cells (cells from a bovine
      lymphoma cell line) and sheep and human erythrocytes. Surprisingly, it
      demonstrated very little activity against two human lymphoma cell lines. In
      contrast, Hly lysed all five cell types tested, each to a greater extent than
      that demonstrated by comparable amounts of Ehx. As with other RTX toxins, Ehx
      activity was calcium dependent and heat labile.

PMID- 8557337
TI  - Human CD4+ and CD8+ T lymphocytes are both cytotoxic to Toxoplasma gondii
      infected cells.
AB  - Studies to determine if Toxoplasma gondii-specific human T cells lyse parasite
      infected cells have yielded conflicting results. Furthermore, attempts to obtain
      human cytotoxic CD8+ T lymphocytes have been difficult because of the lack of a
      reproducible system for their generation. By using paraformaldehyde-fixed, T.
      gondii-infected peripheral blood mononuclear cells as antigen-presenting cells,
      we developed a method whereby T. gondii-specific T-cell lines can be reproducibly
      generated. Six T. gondii-specific T-cell lines were generated from an individual
      chronically infected with T. gondii. Cytofluorometric analysis of these lines
      revealed > 99% CD3+, 85 to 95% CD3+ alpha beta T-cell-receptor-positive (TCR+), 5
      to 9% CD3+ gamma delta TCR+, 50 to 70% CD4+, and 20 to 40% CD8+ cells when cells
      were examined during the first 3 weeks of stimulation and >99% CD3+, >99% CD3+
      alpha beta TCR+, < 1% CD3+ gamma delta TCR+, 20 to 40% CD4+, and 60 to 80% CD8+
      cells when cells were examined between 5 and 11 weeks. Both CD4+ and CD8+ T cells
      had remarkable cytotoxic activity against T. gondii-infected target cells (30 to
      50% specific Cr release at an effector-to-target ratio of 30:1) but not against
      uninfected target cells ( < 10% at an effector-to-target ratio of 30:1).
      Cytotoxic activity by the whole T-cell lines was not T. gondii strain specific.
      Whole T-cell lines were cytotoxic for target cells infected with the C56 and ME49
      strains and the RH strain (which was used to infect peripheral blood mononuclear
      cells). T. gondii-specific T-cell lines displayed the predominant expression of V
      beta 7 TCR. The CDR3 regions of the V beta 7 TCRs of these T-cell lines showed a
      striking degree of sequence identity (oligoclonality). T-cell lines obtained by
      the method reporter here can be used to characterize functional activity of T
      lymphocyte subsets in humans infected with T. gondii.

PMID- 8557338
TI  - Protease cleavage of iron-transferrin augments pyocyanin-mediated endothelial
      cell injury via promotion of hydroxyl radical formation.
AB  - Although a number of bacterium- and host-derived factors have been suggested to
      contribute to the pathogenesis of Pseudomonas aeruginosa-associated tissue
      injury, the mechanism remains unclear. We have previously shown that protease
      modification of iron (Fe)-transferrin generates new iron chelates capable of
      catalyzing hydroxyl radical (.OH) formation from superoxide and hydrogen
      peroxide. The latter two oxidants are generated during redox cycling of another
      P. aeruginosa secretory product, pyocyanin. The lung is a major site of P.
      aeruginosa infection, with damage to local endothelial cells contributing to the
      pathogenesis of such infections. Endothelial cells are highly susceptible to
      oxidant-mediated injury. Therefore, we examined whether pseudomonas elastase
      cleaved Fe-transferrin and pyocyanin synergistically enhance pulmonary artery
      endothelial cell injury via .OH formation. By measuring 51Cr release from
      cultured endothelial cell monolayers, pseudomonas elastase-cleaved Fe-transferrin
      significantly augmented cell injury resulting from cellular exposure to sublethal
      concentrations of pyocyanin. This enhancement in injury was not protease
      specific, as similar results were obtained with pyocyanin in combination with
      trypsin- or porcine pancreatic elastase-cleaved Fe-transferrin. The association
      of iron with the transferrin appeared to be necessary in this process. Supporting
      the involvement of .OH generation via the Haber-Weiss reaction in augmenting cell
      injury, catalase, dimethyl thiourea, superoxide dismutase, deferoxamine, and
      dimethyl sulfoxide significantly inhibited cell injury resulting from exposure to
      pyocyanin and protease-cleaved Fe-transferrin. Furthermore, spin trapping
      demonstrated the production of .OH in this cellular system. We conclude that .OH
      formation resulting from the interaction of protease-cleaved Fe-transferrin and
      endothelial cell redox cycling of pyocyanin may contribute to P. aeruginosa
      associated tissue injury via endothelial cell injury.

PMID- 8557339
TI  - Effect of interleukin 12 neutralization on host resistance and gamma interferon
      production in mouse typhoid.
AB  - Innately resistant (Ityr) A/J mice infected with the virulent Salmonella
      typhimurium C5 strain suppress the early exponential bacterial growth in the
      reticuloendothelial system toward the end of the first week of infection, with
      spleen and liver bacterial counts reaching a plateau phase. In vivo
      administration of neutralizing anti-interleukin-12 (IL-12) antibodies did not
      affect early bacterial growth in the tissues (days 1 to 3) but impaired the
      establishment of the plateau, with higher spleen and liver counts by day 7 of the
      infection in anti-IL-12 treated mice than in untreated controls. Gamma interferon
      (IFN-gamma) was detectable in the sera and spleen homogenates of both control and
      anti-IL-12-treated mice on days 3 and 7 of the infection. Noticeably, IFN-gamma
      levels were significantly lower in anti-IL-12 treated mice than in control
      animals. Splenocytes from uninfected A/J mice released IFN-gamma in response to
      concanavalin A (ConA) or to S. typhimurium C5. In vitro IL-12 neutralization
      dramatically impaired the IFN-gamma response to S. typhimurium but not to ConA.
      Splenocytes harvested from infected anti-IL-12 treated mice on day 7 of the
      infection produced significantly lower amounts of IFN-gamma upon in vitro
      stimulation with ConA and with a Salmonella protein-rich extract than did cells
      from similarly infected untreated control animals. Spleen cells from infected
      mice showed lower proliferative (mitogenic) responses to ConA and to a Salmonella
      soluble extract than did cells from uninfected mice. In vivo anti-IL-12 treatment
      significantly restored the ability of splenocytes from infected mice to
      proliferate in response to the antigens and ConA. In vivo neutralization of IL
      12n in innately susceptible BALB/c mice ((ItyS)) immunized with a live attenuated
      aromatic-dependent Salmonella vaccine reduced host resistance to virulent oral
      challenge with S. typhimurium C5. Thus, in primary Salmonella infections, IL-12
      mediates the suppression of growth of virulent salmonellae in the
      reticuloendothelial system, positively modulates IFN-gamma production, and is
      involved in the immunosuppression which accompanies the acute stages of the
      disease. IL-12 also contributes to host resistance to virulent organisms in
      secondary infections.

PMID- 8557340
TI  - Adherence, fibronectin binding, and induction of cytoskeleton reorganization in
      cultured human cells by Mycoplasma penetrans.
AB  - Mycoplasma penetrans adhered to cultured human cells, forming clusters that
      localized to specific areas of the host cell surface. Adherence and cluster
      formation were inhibited by anti-M. penetrans antibodies, suggesting the
      involvement of specific adhesin-receptor interactions. Ultrastructural studies
      showed that after 2 h of infection, mycoplasmas attach to and penetrate the host
      cell surface. M. penetrans bound selectively to immobilized fibronectin, an
      interaction which was not inhibited by a 70-kDa fragment containing a heparin
      gelatin-binding domain of fibronectin, other matrix glycoproteins, or an RGD
      tripeptide, suggesting the recognition of other specific binding sites on the
      fibronectin molecule. A ca. 65-kDa fibronectin-binding protein of M. penetrans
      was eluted following Sepharose-fibronectin affinity chromatography. Confocal,
      light, and immunofluorescence microscopy demonstrated that the interaction of M.
      penetrans with target cells triggers a signal that causes recruitment of several
      cytoskeletal components, including tubulin and alpha-actinin, and aggregation of
      phosphorylated proteins. Detergent-soluble mycoplasma proteins with apparent
      molecular masses of 18, 28, 32, 36, 39, and 41 kDa selectively bound to
      glutaraldehyde-fixed HEp-2 cells. Our findings offer new insights into
      understanding the interaction of this human mycoplasma with host target cells.

PMID- 8557341
TI  - Vitamin A deficiency predisposes to Staphylococcus aureus infection.
AB  - We have investigated the consequences of vitamin A deficiency in a rat model of T
      cell-dependent and superantigen-mediated Staphylococcus aureus arthritis. After
      intravenous inoculation of enterotoxin A-producing staphylococci, the vitamin-A
      deficient rats showed a decreased weight gain compared with the paired fed
      controls despite equal food consumption. The control rats developed arthritis in
      the first few days after bacterial inoculation, with a peak frequency at day 5,
      and then gradually recovered; however, the frequency of arthritis 18 days after
      bacterial inoculation was 86% among the vitamin A-deficient rats and 44% among
      the control rats. During this period, 3 of 10 deficient rats and 1 of 10 control
      rats died. Further in vitro analysis revealed that T-cell responses to S. aureus
      were significantly higher in the vitamin A-deficient rats than in the control
      animals. In contrast, B-cell reactivity, measured as immunoglobulin levels,
      autoantibody levels, and specific antibacterial antibody levels in serum, did not
      differ between the groups. Interestingly, the innate host defense mechanisms
      against S. aureus were also profoundly affected by vitamin A deficiency. Thus,
      despite a larger number of circulating phagocytic cells in the vitamin-A
      deficient group, the capacity to phagocytize and exert intracellular killing of
      S. aureus was significantly decreased in comparison with the control rats.
      Furthermore, serum from the vitamin A-deficient rats inoculated with
      Staphylococcus aureus displayed decreased complement lysis activity. Our results
      suggest that the increased susceptibility to S. aureus infection observed in the
      vitamin-A-deficient rats is due to a concerted action of antigen-specific T-cell
      hyperactivity, impaired function of the phagocytes, and decreased complement
      activity.

PMID- 8557342
TI  - Chagas' disease is attenuated in mice lacking gamma delta T cells.
AB  - The role of gamma delta T cells in the immunopathology of Chagas' disease is
      evaluated by monitoring the course of Trypanosoma cruzi infection in mice lacking
      gamma delta T cells after disruption of the T-cell receptor C delta locus. Levels
      of parasitemia, states of lymphocyte activation, and levels of lymphokine
      production as well as tissue pathology are compared in delta knockout mice and
      their littermates in acute and chronic phases of infection. Although the levels
      of circulating parasites do not significantly differ in the two groups, mortality
      scores and numbers of inflammatory lesions of skeletal and cardiac muscles are
      lower in gamma delta T cell-deficient m ice than in littermate controls.
      Furthermore, polyclonal lymphocyte activation, as measured by proliferative
      activities and numbers of B- and T-cell blasts in the spleen, are reduced in
      deficient mice in the acute and chronic phases of infection. Levels of gamma
      interferon mRNA obtained from total spleen cells, known to be a critical
      lymphokine in resistance to T. cruzi infection, are significantly higher in
      uninfected gamma delta T cell-deficient mice than in control animals and slightly
      above levels for littermates in the course of acute infection. Interestingly,
      however, in chronic phases, the levels of this lymphokine are not statistically
      different between the two groups of mice. These results indicate that gamma delta
      T cells do not play a crucial role in parasite clearance during the acute phase
      of the disease but contribute to the mechanisms leading to tissue damage and
      pathology.

PMID- 8557343
TI  - The Salmonella dublin virulence plasmid does not modulate early T-cell responses
      in mice.
AB  - The virulence plasmid in Salmonella dublin mediates systemic infection in mice
      and cattle. The role of gamma delta T cells or hepatic extrathymic T cells has
      recently been reported to be important in the control of the early stage of
      Salmonella choleraesuis infections of mice. Here, we report on T-cell responses
      in conventional mice after challenge with a virulent strain of S. dublin carrying
      a virulence plasmid or with a strain cured of the plasmid. Over a period of 4
      days postinfection, when both strains could be compared, similar changes in alpha
      beta and gamma delta T-cell subsets in peritoneal cavities, livers, and spleens
      were recorded, demonstrating no clear role of the virulence plasmid in modulation
      of early T-cell responses. To investigate further the role of the virulence
      plasmid in pathogenesis, the growth of the plasmid-cured strain was assessed in
      SCID, SCID bg, and irradiated mice. During the first 6 days after infection,
      there was no statistically difference in the net growth of Salmonella cells in
      the livers and spleens of SCID and SCID bg mice compared with conventional
      BALB/mice. This observation excludes a key role for a T- or B-cell-mediated
      immune response in controlling the initial growth of the plasmid-cured S. dublin
      strain. Thereafter, the immunocompromised mice were no longer able to control
      infection, although SCID mice were more efficient at controlling net bacterial
      multiplication than SCID bg mice, potentially implicating NK cells in the control
      of infection in SCID mice. The early control of net bacterial multiplication in
      the spleens and livers of BALB/c mice was ablated by whole-body X-irradiation.
      Both wild-type and plasmid-cured strains multiplied significantly more rapidly in
      irradiated than in conventional BALB/c mice. However, the numbers of wild-type
      bacterial still increased more rapidly than in the numbers of the cured strains.
      These results are consistent with a role of the S. dublin virulence plasmid in
      promoting in vivo growth of Salmonella cells.

PMID- 8557344
TI  - Further characterization of delta aroA delta virG Shigella flexneri 2a strain CVD
      1203 as a mucosal Shigella vaccine and as a live-vector vaccine for delivering
      antigens of enterotoxigenic Escherichia coli.
AB  - The use of attenuated delta aroA delta virG Shigella flexneri 2a strain CVD 1203
      as a live vector for enterotoxigenic Escherichia coli (ETEC) antigens is
      reported. CVD 1203 alone or expressing colonization factor antigen fimbriae and
      CS3 fibrillae of ETEC was given to guinea pigs and mice, orogastrically (o.g.) or
      intranasally (i.n.). CVD 1203 given i.n. elicited high titers of
      antilipopolysaccharide (anti-LPS) immunoglobulin A (IgA) and was protective in
      guinea pigs against a homologous conjunctival challenge. Whereas a strong IgA
      response against colonization factor antigen CS3, and Shigella LPS was detected
      in tears and serum of guinea pigs after o.g. or i.n. immunization, the i.n. route
      elicited significantly higher antibody titers. A strong serum IgG response was
      also observed against the ETEC antigens, although no serum anti-LPS IgG response
      was detected. The immune response in mice followed a pattern similar to that in
      guinea pigs, and the difference between the responses after o.g. and i.n.
      administration was even more remarkable.

PMID- 8557345
TI  - Purification, characterization, and primary structure of Clostridium perfringens
      lambda-toxin, a thermolysin-like metalloprotease.
AB  - The lambda-toxin of Clostridium perfringens type B NCIB10691 was purified by
      ammonium sulfate precipitation, followed by size exclusion, anion-exchange, and
      hydrophobic interaction chromatography. The purified toxin had an apparent
      molecular mass of 36 kDa, as determined by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis. The toxin possessed casein-hydrolyzing activity, which was
      inhibited specifically by metal chelators, indicating that the toxin is a
      metalloprotease. The gene encoding the lambda-toxin (lam), which was shown by
      Southern analysis to be located on a 70-kb plasmid, was cloned into Escherichia
      coli cells. Nucleotide and N-terminal amino acid sequencing revealed that the lam
      gene encodes a 553-amino-acid protein, which is processed into a mature form, the
      molecular mass of which was calculated to be 35,722 Da. The deduced amino acid
      sequence of the mature enzyme contains an HEXXH motif characteristic of zinc
      metalloproteases and is homologous to other known enzymes belonging to the
      thermolysin family. The purified toxin degraded various biologically important
      substances, such as collagen, fibronectin, fibrinogen, immunoglobulin A, and the
      complement C3 component. It caused an increase in vascular permeability and
      hemorrhagic edema on injection into the dorsal skin of mice. These results
      suggest that the toxin contributes to the pathogenesis of histolytic infection by
      lambda-toxin-producing C. perfringens.

PMID- 8557346
TI  - Role of the host in pathogenesis of Helicobacter-associated gastritis: H. felis
      infection of inbred and congenic mouse strains.
AB  - In humans, Helicobacter pylori establishes a chronic infection which can result
      in various degrees of gastric inflammation, peptic ulcer disease, and a
      predisposition to gastric cancer. It has been suggested that bacterial virulence
      factors such as the vacuolating toxin (VacA) and the cytotoxin-associated gene
      product (CagA) may play a major role in determining the clinical outcome of
      Helicobacter infections. The role of host responses in these varied outcomes has
      received little attention. Helicobacter felis, which does not express CagA or
      VacA, causes chronic infection and inflammation in a well-characterized mouse
      model. We have used this model to evaluate the role of host responses in
      Helicobacter infections. BALB/c, C3H, and C57BL/6 mice were orally infected with
      a single strain of H. felis, and 2 and 11 weeks after infection, the mice were
      sacrificed and evaluated histologically for magnitude of H. felis infection.
      Intensity and extent of inflammation, and cellular composition of the
      inflammatory infiltrate. All three strains of mice demonstrated comparable levels
      of infection at 11 weeks, but the pattern and intensity of inflammation varied
      from minimal in BALB/c mice to severe in C57BL/6 mice. Gastric epithelial
      erosions were noted in C3H mice, and mucous cell hyperplasia was observed in C3H
      and C57BL/6 mice. Abundant mucosal mast cells were observed in the gastric
      tissues of all three mouse strains. Studies using major histocompatibility
      complex (MHC)-congenic mice revealed probable contributions by both MHC and non
      MHC genes to Helicobacter-induced inflammation. Thus, large variations in the
      severity of disease were observed after infection of different inbred strains and
      congenic mice with a single isolate of H. felis. These results demonstrate the
      importance of the host response in disease outcome following gastric Helicobacter
      infection.

PMID- 8557347
TI  - Responses to vaccination in strains of mice that differ in susceptibility to
      coccidiosis.
AB  - BALB/c mice are normally resistant to infection with Eimeria vermiformis than
      C57BL/6 (B6) mice, but these phenotypes were reversed by prior vaccination with
      crude antigens prepared from developmental stages of the parasite: B6 mice were
      protected, and BALB/c mice were made more susceptible. Infections with a
      heterologous species, E. pragensis, were unaffected when this was given either
      alone or together with E. vermiformis. In both strains of mice, vaccination
      induced serum antibody responses to E. vermiformis and the levels were boosted by
      superimposed infection, the highest values being found in BALB/c mice. Cellular
      responses in the mesenteric lymph nodes (MLN), as indicated by cellularity and
      proliferation, either unstimulated or restimulated in vitro with E. vermiformis
      antigen, were decreased in both strains, but markedly more in BALB/c than B6. The
      capacity of MLN cells to transfer immunity to naive recipients was lowered by
      vaccination of BALB/c donors but unimpaired in vaccinated B6 mice. Responses to
      the mitogen, concanavalin A, and to unrelated antigens (human erythrocytes and
      fowl gamma globulin) were unaffected. Thus, parenteral vaccination, which
      increased the susceptibility of BALB/c mice to infection with E. vermiformis, had
      a depressing effect on some specific immune responses in the MLN. It was
      surprising to find some reduction in the cellular responses of the MLN of B6 mice
      also, although they were protected by vaccination.

PMID- 8557348
TI  - A recombinant baculovirus 42-kilodalton C-terminal fragment of Plasmodium
      falciparum merozoite surface protein 1 protects Aotus monkeys against malaria.
AB  - The immunogenicity and protective efficacy of baculovirus recombinant polypeptide
      based on the Plasmodium falciparum merozoite surface protein 1 (MSP-1) has been
      evaluated in Aotus lemurinus griseimembra monkeys. The MSP-1-based polypeptide,
      BVp42, corresponds to the 42-kDa C-terminal processing fragment of the precursor
      molecule. Immunization of Aotus monkeys with BVp42 in complete Freund's adjuvant
      resulted in high antibody titers against the immunogen as well as parasite MSP-1.
      Fine specificity studies indicated that major epitopes recognized by these
      antibodies localize to conserved determinants of the 19-kDa C-terminal fragment
      derived from cleavage of the 42-kDa processing fragment. Effective priming of MSP
      1-specific T cells was also demonstrated in lymphocyte proliferation assays. All
      three Aotus monkeys immunized with BVp42 in complete Freund's adjuvant showed
      evidence of protection of protection against blood-stage challenge with P.
      falciparum. Two animals were completely protected, with only one parasite being
      detected in thick blood films on a single days after injection. The third animal
      had a modified course of infection, controlling its parasite infection to levels
      below detection by thick blood smears for an extended period in comparison with
      adjuvant control animals. All vaccinated, protected Aotus monkeys produced
      antibodies which inhibited in vitro parasite growth, indicating that this assay
      may be a useful correlate of protective immunity and that immunity induced by
      BVp42 immunization is mediated, at least in part, by a direct effect of
      antibodies against the MSP-1 C-terminal region. The high level of protection
      obtained in these studies supports further development of BVp42 as a candidate
      malaria vaccine.

PMID- 8557349
TI  - A glyceraldehyde-3-phosphate dehydrogenase homolog in Borrelia burgdorferi and
      Borrelia hermsii.
AB  - A polyreactive monoclonal antibody recognized a 38.5-kDa polypeptide with amino
      terminal sequence identity to conserved regions of glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) in Borrelia burgdorferi, the Lyme disease agent, and
      Borrelia hermsii, an agent of American relapsing fever. This monoclonal antibody
      also recognized GAPDH from other pathogenic spirochetes and other prokaryotes and
      eukaryotes as well. GAPDH activity was detected in sonicates of both B.
      burgdorferi and B. hermsii but not in live, intact organisms, indicating the
      possibility of a subsurface localization for the Borrelia GAPDH activity.
      Degenerate primers constructed from highly conserved regions of gapdh of other
      prokaryotes successfully amplified this gene homolog in both B. burgdorferi and
      B. hermsii. Nuclei acid and deduced amino acid sequence analysis of the 838-bp
      probes for each borrelia indicated 93.9% identity between B. burgdorferi and B.
      hermsii at the amino acid level. Amino acid identities of B. burgdorferi and B.
      hermsii with Bacillus stearothermophilus were 59.2% and 58.8% respectively.
      Southern hybridization studies indicated that the gene encoding GAPDH is located
      on the chromosome of each borrella. In other bacterial species, GAPDH has other
      functions in addition to its traditional enzymatic role in the glycolytic
      pathway. GAPDH may play a similar role in borrelias.

PMID- 8557350
TI  - Intracellular growth and cytotoxicity of Mycobacterium haemophilum in a human
      epithelial cell line (Hec-1-B).
AB  - We developed an in vitro model to study the temperature-regulated cytotoxicity
      and intracellular growth of Mycobacterium haemophilum in cultured human
      epithelial and endothelial cells. M. haemophilum associated with human epithelial
      and endothelial cells at similar rates when incubated at 33 and 37 degrees C, but
      only the epithelial cell line supported the multiplication of this organism. M.
      haemophilum grew equally well with epithelial cells at both temperatures. The
      aminoglycoside antibiotic amikacin was used to study the intracellular growth of
      M. haemophilum in the epithelial cells at 33 and 37 degrees C. Although an
      approximately equal number of bacteria were found within cells after 2 days of
      incubation at both temperatures, intracellular replication of M. haemophilum was
      1,000-fold greater at 33 than at 37 degrees C. This intracellular multiplication
      was associated with destruction of the monolayers at 33 but not at 37 degrees C,
      and only culture filtrates from infected monolayers incubated at 33 degrees C
      were cytotoxic to fresh epithelial cell monolayers. This strain of M. haemophilum
      also produced contact-dependent hemolysis of sheep erythrocytes, demonstrating
      the possible presence of a cytolysin. These studies suggest that M. haemophilum
      has a preference for growth with cultured human epithelial cells. In addition,
      intracellular growth is best at 33 degrees C in epithelial cells, and this
      correlated with cytotoxicity at this temperature. This phenotype may be caused by
      induction of a soluble cytotoxic component, possibly a hemolytic cytolysin.

PMID- 8557351
TI  - Characterization of Tn917 insertion mutants of Staphylococcus epidermidis
      affected in biofilm formation.
AB  - Biofilm formation is thought to result from the concerted action of primary
      attachment to a specific surface and accumulation in multilayered cell clusters.
      Here we describe the isolation and characterization of transposon (Tn917) mutants
      of Staphylococcus epidermidis O-47 which were biofilm negative in the polystyrene
      microtiter plate assay. Among 5,000 Tn917 insertion mutants, 4 biofilm-negative
      mutants were isolated. Each mutant carried one copy of Tn917. The mutants were
      divided into two phenotypic classes: class A (mut1 and mut1a) and class B (mut2
      and mut2a). Mutants of phenotypic class A lacked four cell surface proteins, were
      less hydrophobic, and were affected in primary attachment to polystyrene, but
      were still able to form multilayered cell clusters. They were able to form a
      biofilm on a glass surface, a trait that was even more pronounced than in the
      wild-type stain O-47. Loss of several surface proteins might have led to the
      reduced surface hydrophilic structures, thus favoring primary attachment to a
      glass surface and leading to subsequent biofilm formation. Mutants of phenotype
      class B were able to attach to polystyrene but were unable to form multilayered
      cell clusters, had unchanged cell surface proteins and hydrophobicity, and were
      unable to form a biofilm on a glass surface, mut1 and mut2 could be complemented
      by wild-type DNA fragments containing the Tn917 insertion sites of mut1 and mut2,
      respectively. The complemented biofilm-positive clone mut1 (pRC20) produced a 60
      kDa protein which is postulated to function as the adhesin for binding to
      plastic. The traits of binding to polystyrene and the ability to form
      multilayered cell clusters are phenotypically and genetically distinct.

PMID- 8557353
TI  - Vibrio cholerae Hcp, a secreted protein coregulated with HlyA.
AB  - Hcp is a 28-kDa secreted protein of Vibrio cholerae regulated coordinately with
      the hemolysin, HlyA. Both proteins show a dependence on HlyU for expression,
      suggesting that Hcp may be secreted by V. cholerae in vivo. We have identified
      and sequenced two genes for Hcp, designated hcpA and hcpB (hemolysin-coregulated
      protein). The genes encode identical amino acid sequences. Both express a 28-kDa
      protein, despite open reading frames with only a 19-kDa capacity, suggesting that
      the Hcp protein runs aberrantly on polyacrylamide gel electrophoresis. There is
      no cleavage involved in secretion of Hcp from the cell, suggesting a novel
      mechanism of secretion. An hcp null mutant was constructed, and this strain
      displayed no deficiency in virulence or colonization in the infant mouse cholera
      model. From sequence data and primer extension analysis, we predict that the hcp
      promoter is the sigma 54 type, with a candidate integration host factor binding
      site upstream. Although hcp and hlyA are coregulated by HlyU, there are no
      obvious similarities between their promoters. We predict that an intermediate
      regulator may be involved in the activation of hcp by HlyU. This raises the
      possibility that HlyU is part of a regulatory cascade.

PMID- 8557352
TI  - Immunologic characteristics of a Streptococcus mutans glucosyltransferase B
      sucrose-binding site peptide-cholera toxin B-subunit chimeric protein.
AB  - Glucosyltranferases (Gtfs) produced by the mutans streptococci are recognized as
      virulence factors in dental caries, and the inhibition of Gtfs by secretory
      immunoglobulin A is predicted to provide protection against this disease. The
      basis of such mucosal immunity is linked to the ability to reliably stimulate
      production of secretory immunoglobulin A against Gtfs. In this regard, we are
      exploring the immunogenicities of various Gtf peptides genetically fused to the B
      subunit of cholera toxin (CTB), a known mucosal adjuvant. In this work, we have
      created a gene fusion linking the GtfB active-site (AS) peptide
      DANFDSIRVDAVDNVDADLLQIA to the amino terminus of CTB. This sequence, deduced from
      the nucleotide sequence of gtfB from Streptococcus mutans GS5, has been found to
      be strongly conserved in Gtfs from several mutans streptococci. We have purified
      this recombinant protein (AS:CTB) from Escherichia coli carrying the fusion gene
      under the control of the lactose operon promoter. This protein was immunogenic in
      rabbits and produced specific serum antibodies against both the Gtf peptide and
      the CTB moiety. The antiserum was tested for its ability to inhibit GtfB activity
      obtained from a mutant of S. mutans able to make only this enzyme and none of the
      other usual Gtfs or fructosyltransferase. Approximately 50% of the GtfB activity
      was inhibited in such assays. These results suggest that the AS of this enzyme is
      accessible to antibody binding and that this region of the protein may be
      considered a vulnerable target for vaccine design and development. The AS:CTB was
      able to bind GM1, ganglioside in enzyme-linked immunosorbent assays, indicating
      that the recombinant protein retained this property, which is though to be
      critical to the mucosal immunoadjuvant properties of CTB. Thus, this protein may
      be promising as a candidate anticaries vaccinogen alone or in combination with
      other Gtf peptides or conjugates.

PMID- 8557354
TI  - Antigenic differences associated with genetically distinct Pneumocystis carinii
      from rats.
AB  - Pneumocystis carinii is a family of organisms found in a wide variety of
      mammalian lungs. In immunocompromised hosts, the organisms are able to produce an
      oftentimes fatal pneumonia. The existence of distinct types of Pneumocystis
      populations is strongly supported by antigenic and genetic evidence. In the
      present study, we assessed the antigenic profiles of two genetically distinct
      Pneumocystis carinii populations, P. carinii f. sp. carinii and P. carinii f. sp.
      ratti, as well as two types of P. carinii f. sp. carinii defined by
      electrophoretic karyotyping (forms 1 and 2). The separated and blotted proteins
      of the organism preparations were probed with four monoclonal antibodies (MAbs)
      generated to the major surface glycoproteins of rat-derived P. carinii, one anti
      human P. carinii MAb, and two polyclonal antisera made with rat-derived P.
      carinii as the immunogen. Differences in reactivities between the P. carinii f.
      sp. carinii and P. carinii f. sp. ratti preparations were detected with two of
      the MAbs, and both of the rat P. carinii polyclonal antisera in the 45- to 55-kDa
      molecular mass range, but not with the human P. carinii MAb. The reactivities of
      the 16 P. carinii f. sp. carinii preparations were the same with two exceptions.
      Two preparations of form 1 showed strong reactivity with the anti-MSG MAb RA-C11.
      The ratios of cyst forms to trophic forms evaluated by microscopy were not
      associated with any of the differences observed in the antigenic profiles. The
      antigenic differences between P. carinii f. sp. carinii and P. carinii f. sp.
      ratti are consistent with the distinction of these two populations made by
      molecular genetic techniques, while the two differences detected among the P.
      carinii f. sp. carinii preparations suggest the organism may be able to modulate
      antigenic epitopes. The use of immunoblotting to differentiate infecting organism
      populations and assess antigenic modulation holds promise for future
      epidemiologic studies.

PMID- 8557355
TI  - T-cell responses to outer membrane proteins of Neisseria meningitidis:
      comparative study of the Opa, Opc, and PorA proteins.
AB  - Former studies have shown that the class 5 outer membranes proteins (Opa and Opc
      proteins) of Neisseria meningitidis are at least as immunogenic as meningococcal
      porin proteins. High antibody titers to class 5 proteins have been observed in
      sera obtained during convalescence after meningococcal infection. A strong
      increase in anti-class 5 antibodies has also been observed in vaccinees who
      received a meningococcal outer membrane vesicle preparation. The enhanced B-cell
      response to class 5 proteins may be due to the presence of immunodominant helper
      T-cell epitopes in these proteins. In order to investigate this hypothesis, we
      tested purified Opa, Opc, and class 1 proteins for recognition by human T cells.
      a hierarchy of T-cell immunogenicity was observed among the outer membrane
      proteins, the Opa protein being more immunogenic than the other proteins. In most
      cases, the proliferative responses elicited by Opc were higher than the responses
      observed for the class 1 protein. The epitopes recognized by the immune T cells
      were identified by using overlapping synthetic peptides spanning the protein
      sequences of OpaB, Opa5d, and Opc.

PMID- 8557356
TI  - Augmented immunological activities of recombinant lipopolysaccharide possessing
      the mannose homopolymer as the O-specific polysaccharide.
AB  - Recombinant lipopolysaccharide possessing the mannose homopolymer as the O
      specific polysaccharide was manufactured genetically by transforming Escherichia
      coli K-12 with various rfb genes capable of synthesizing the mannose homopolymer.
      Recombinant lipopolysaccharide exhibited levels of anticomplement activity,
      adjuvant activity, and regional lymph node-enlarging activity much higher than
      those exhibited by the original rough-type lipopolysaccharide from E. coli K-12
      or lipopolysaccharide possessing the heteropolysaccharide from E. coli O111.
      Immunological activities of recombinant lipopolysaccharide were as strong as
      those of wild-type lipopolysaccharide possessing the mannose homopolymer.
      Characteristic activities of wild-type lipolysaccharide possessing the mannose
      homopolymer were exhibited by recombinant lipopolysaccharide. The abilities of
      lipopolysaccharide to activate B cells polyclonally and to produce cytokines did
      not seem to be related to the presence of the mannose homopolymer. Therefore, it
      was suggested that the mannose homopolymer in the O-specific polysaccharide might
      exclusively enhance anticomplement activity, adjuvant activity, and regional
      lymph node-enlarging activity among various lipid A activities.

PMID- 8557358
TI  - Intracellular fate of Mycobacterium avium: use of dual-label spectrofluorometry
      to investigate the influence of bacterial viability and opsonization on
      phagosomal pH and phagosome-lysosome interaction.
AB  - Mycobacterium avium is a facultative intracellular pathogen that can survive and
      replicate within macrophages. We tested the hypotheses that survival mechanisms
      may include alteration of phagosomal pH or inhibition of phagosome-lysosome
      fusion. M. avium was surface labeled with N-hydroxysuccinimidyl esters of
      carboxyfluorescein (CF) and rhodamine (Rho) to enable measurement of the pH of
      individual M. avium-containing phagosomes and the interactions of bacterium
      containing phagosomes with labeled secondary lysosomes. CF fluorescence is pH
      sensitive, whereas Rho is pH insensitive; pH can be calculated from their
      fluorescence ratios. Surface labeling of M. avium did not affect viability in
      broth cultures or within J774, a murine macrophage-like cell line. By
      fluorescence spectroscopy, live M. avium was exposed to an environmental pH of
      approximately 5.7 at 6 h after phagocytosis, whereas similarly labeled Salmonella
      typhimurium, zymosan A, or heat-killed M. avium encountered an environmental pH
      of < 5.0. Video fluorescence and laser scanning confocal microscopy gave
      consistent pH results and demonstrated the heterogeneity of intracellular fate
      early in infection. pH became more homogeneous 6 h after infection. M. avium
      cells were coated with immunoglobulin G (IgG) or opsonized to investigate whether
      phagocytosis by the corresponding receptors would alter intracellular fate.
      Opsonized, unopsonized, and IgG-coated M. avium cells entered compartments of
      similar pH. Finally, the spatial distribution of intracellular bacteria and
      secondary lysosomes was compared. Only 18% of live fluorescent M. avium cells
      colocalized with fluorescent lysosomes, while 98% of heat-killed bacteria
      colocalized. Thus, both inhibition of phagosome-lysosome fusion and alteration of
      phagosomal pH may contribute to the intracellular survival of M. avium.

PMID- 8557357
TI  - Staphylococcus aureus binding to human nasal mucin.
AB  - Colonization of human nasal mucosa with Staphylococcus aureus sets the stage for
      subsequent systemic infection. This study characterizes S. aureus adhesion to
      nasal mucosa in vitro and investigates the interaction of S. aureus with human
      nasal mucin. S. aureus binding to cell-associated and cell-free mucus was greater
      than to nonmucin-coated epithelial cells. Scanning electron microscopy of S.
      aureus incubated with human nasal mucosal tissue showed minimal binding to
      ciliated respiratory epithelium. In a solid-phase assay, S. aureus bound to
      purified human nasal mucin-coated wells significantly more than to bovine serum
      albumin-coated microtiter wells. Binding to mucin was saturable in a dose- and
      time-dependent fashion. Staphylococcal adherence to human nasal mucin was
      inhibited by bovine submaxillary mucin but not by fibrinogen. Pretreatment of
      mucin with periodate but not with pronase reduced adherence. Trypsin treatment of
      the bacteria significantly reduced adherence to mucin. 125I-labelled nasal mucin
      bound to two surface proteins (138 and 127 kDa) of lysostaphin-solubilized S.
      aureus. Binding to human nasal mucin occurs in part via specific adhesin-receptor
      interactions involving bacterial proteins and the carbohydrate moiety in mucin.
      These experiments suggest that S. aureus binding to mucin may be critical for
      colonization of the nasopharyngeal mucosa.

PMID- 8557359
TI  - Primary structure of the variable region of monoclonal antibody 2B10, capable of
      inducing anti-idiotypic antibodies that recognize the C-terminal region of MSA-1
      of Plasmodium falciparum.
AB  - Previously, we reported on the properties of a monoclonal antibody, 2B10, which
      has the same determinant on the human erythrocyte as MSA-1 of Plasmodium
      falciparum (FCR3 strain); the binding of both ligands to erythrocyte receptors
      was totally sialic acid dependent. In this work, rabbit anti-2B10 idiopathic
      antibodies were generated. The anti-idiotypic antibodies recognized both the
      erythrocyte binding site of 2B10 and the C-terminal region of MSA-1 (amino acids
      1047 to 1640); they were able to inhibit 2B10 and MSA-1 binding to erythrocytes
      and partially prevent P. falciparum merozoites from invading erythrocytes. The
      utility of 2B10 in the study of the interaction between MSA-1 and human
      erythrocytes prompted us to determine the nucleotide and deduced amino acid
      sequences of its VH and VL regions. The data show that the 2B10 VH region is part
      of the J558 family and is especially homologous to BALB/c anti-nitrophenyl
      monoclonal antibody 21.1.43; the VL region belongs to the VK1 subgroup and comes
      from the same genomic locus as (NZB x W)F1 anti-DNA and C57BL anti-dextran
      monoclonal antibodies BXW-14 and 42.48.12.2, respectively. Most of the
      differences among the VH and VL segments are located in CDR1 and -3. The binding
      site of 2B10 contains both negatively and positively charged amino acid residues.
      The amino acid sequences of the 2B10 VH region and a region of MSA-1 from the
      Wellcome strain of P. falciparum (amino acids 1002 to 1115) share 43% similarity,
      and the amino acid sequences between the 2B10 VL region and another segment of
      the same MSA-1 (amino acids 1247 to 1394) share 48% similarity. We conclude that
      the interactions between erythrocyte receptors and their ligands, 2B10 and MSA-1,
      are related and that the C-terminal region of MSA-1 is the erythrocyte binding
      domain.

PMID- 8557361
TI  - Antibody against the capsule of Vibrio cholerae O139 protects against
      experimental challenge.
AB  - Antiserum to the capsular polysaccharide of an opaque variant of Vibrio cholerae
      O139 strain MDO-12 recognizes capsular antigen in three different colonial
      variants of the strain, although the amount of recognition varies with the extent
      of opacity. The anti-capsular-polysaccharide serum, at subagglutinating doses,
      protected suckling mice against challenge with both the most opaque variant and
      the most translucent variant. Further studies indicated that the protection was
      associated with inhibition of intestinal colonization by the vibrios. These
      results thus highlight the potential importance of the capsule in
      immunoprophylaxis against cholera caused by V. cholerae O139.

PMID- 8557360
TI  - Characterization of 20K fimbria, a new adhesin of septicemic and diarrhea
      associated Escherichia coli strains, that belongs to a family of adhesins with N
      acetyl-D-glucosamine recognition.
AB  - Bovine septicemic Escherichia coli 31A agglutinates bovine, rabbit, and human
      erythrocytes and adheres in vitro to the brush border of bovine or ovine
      intestinal epithelial cells and to the human colon carcinoma Caco-2 cell line.
      The adhesion and hemagglutination of E. coli 31A are mediated by a chromosome
      encoded fimbrial adhesin serologically distinct from known fimbrial adhesins
      found in enterotoxigenic and septicemic bovine E. coli strains. By electron
      microscopy studies the fimbriae designated 20K were observed as fine flexible
      filaments (diameter, 3 nm) and the purified major fimbrial subunit appeared with
      an apparent molecular mass of 20,000 Da. Western blot (immunoblot) analysis, N
      terminal sequence alignment, and amino acid composition revealed a high homology
      with the N-acetyl-D-glcosamine-specific G fimbria of human uropathogenic E. coli
      and with fimbriae belonging to the F17 family produced by bovine enterotoxigenic
      and invasive E. coli strains. Immunological study revealed that 20K fimbria was
      closely related to G fimbria and represents a serological variant of F17 fimbria.
      Hemagglutination and adhesion inhibition assays demonstrated that 20K, G, and F17
      fimbriae bind to an N-acetyl-D-glucosamine-containing receptor, but each probably
      binds to different oligosaccharide sequences or different receptors on host
      tissues. 20K fimbriae were produced by a limited group of clonally related
      strains with the unusual m-inositol-positive phenotype and appeared highly
      associated with the plasmid-mediated virulence factor. An examination of natural
      occurrence of 20K fimbriae among a large collection of human and animal
      pathogenic E. coli showed that 20K fimbria is the prominent adhesin among bovine
      septicemic E. coli isolated from European countries.

PMID- 8557362
TI  - A nontoxic cholera enterotoxin (CT) analog is chimeric with regard to both
      epitypes of CT-B subunits, CT-B-1 and CT-B-2.
AB  - The gene encoding a nontoxic analog, CT-2*, of cholera enterotoxin (CT) with
      attenuating codon substitutions in the A subunit was introduced into the
      attenuated Vibrio cholerae classical biotype mutant candidate vaccine strain
      CVD103, which produces the B subunit (but not the A subunit) of CT-1. The
      recombinant strain produces a chimeric nontoxic analog holotoxin containing both
      CT-B-1 and CT-B-2 subunits. This offers potential advantages over CVD103 in the
      induction of immunity against E1 Tor biotype and V. cholerae O139 strains which
      produce CT-B-2. The recombinant protein may also be useful in polysaccharide
      protein conjugate vaccines against both O1 and O139 serovars of V. cholerae.

PMID- 8557363
TI  - Complete development of Cryptosporidium parvum in bovine fallopian tube
      epithelial cells.
AB  - Cryptosporidium parvum is a coccidian parasite responsible for causing protracted
      and life-threatening diarrheal illness in immunocompromised humans, especially
      patients with AIDS. The lack of medications effective in treating people
      suffering from cryptosporidiosis has prompted the development of in vivo and in
      vitro models for this disease. This study is the first to demonstrate that C.
      parvum can complete its entire life cycle (from sporozoite to infective oocyst)
      in a primary culture of bovine fallopian tube epithelial (BFTE) cells. Scanning
      and transmission electron photomicrographs were used to detail the ultrastructure
      of individual parasitic stages. Successful infections were produced by
      inoculating cell cultures with either oocysts or purified sporozoites. Infection
      of BFTE cells with C. parvum close paralleled in vivo infections with regard to
      host cell location and chronology of parasite development. Infecting BFTE cells
      with sporulated oocysts provided a reproducible and quantitative cultivation
      system with significantly (P < or = 0.001) higher infection rates than in Madin
      Darby canine kidney cells. Oocysts produced in BFTE cells were infective for
      immunosuppressed adult C57BL/6N mice. Cultivation of C. parvum in BFTE cells will
      facilitate the study of interactions between parasites and host cells as well as
      provide a reliable system for evaluating anticryptosporidial compound efficacy.

PMID- 8557364
TI  - Protective immunity to Shiga-like toxin I following oral immunization with Shiga
      like toxin I B-subunit-producing Vibrio cholerae CVD 103-HgR.
AB  - This study addresses a mechanism for inducing systemic immunity to Shiga-like
      toxins by oral administration of a Shiga-like toxin I B-subunit-expressing Vibrio
      cholerae vaccine strain [CVD 103-HgR(pDA60)]. Two sets of three rabbits were
      given either CVD 103-HgR or CVD 103-HgR(pDA60) orally. All rabbits immunized with
      CVD 103-HgR(pDA60) developed neutralizing serum antibodies to Shiga-like toxin I.
      None of the controls developed such antibodies.

PMID- 8557365
TI  - Phospholipase C and perfringolysin O from Clostridium perfringens upregulate
      endothelial cell-leukocyte adherence molecule 1 and intercellular leukocyte
      adherence molecule 1 expression and induce interleukin-8 synthesis in cultured
      human umbilical vein endothelial cells.
AB  - Clostridium perfringens phospholipase C (PLC) and perfringolysin O (PFO)
      differentially induced human umbilical vein endothelial cell expression and
      synthesis of endothelial cell-leukocyte adherence molecule-1 (ELAM-1),
      intracellular leukocyte adherence molecule-1 (ICAM-1), and interleukin-8 (IL-8).
      PLC strongly induced expression of ELAM-1, ICAM-1, and IL-8, while PFO stimulated
      early ICAM-1 expression but did not promote ELAM-1 expression or IL-8 synthesis.
      PLC caused human umbilical vein endothelial cells to assume a fibroblastoid
      morphology, whereas PFO, in high concentrations or after prolonged low-dose toxin
      exposure, caused cell death. The toxin-induced expression of proadhesive and
      activational proteins and direct cytopathic effects may contribute to the
      leukostasis, vascular compromise, and capillary leak characteristics of C.
      perfringens gas gangrene.

PMID- 8557366
TI  - P55, an immunogenic but nonprotective 55-kilodalton Borrelia burgdorferi protein
      in murine Lyme disease.
AB  - Immunization of C3H mice with P55 (previously called S1), a 55-kDa Borrelia
      burgdorferi antigen that is immunogenic after infection, elicited a strong
      antibody response but did not protect mice against B. burgdorferi challenge. Mice
      immunized with a P55 fusion protein in complete Freund's adjuvant developed anti
      P55 antibodies, detectable at a titer of 1:10,000 by immunoblotting. To
      determine, if a protective response had been elicited, P55-vaccinated mice were
      fed upon by ticks infected with B. burgdorferi. The frequency of B. burgdorferi
      infection was similar in P55-immunized and control mice, and spirochetes were not
      destroyed within ticks that fed on P55-vaccinated mice. P55 is an immunogenic
      antigen that does not induce a protective response in the vertebrate or
      invertebrate host.

PMID- 8557367
TI  - Reconstitution of B-cell-depleted mice with B cells restores Th2-type immune
      responses during Plasmodium chabaudi chabaudi infection.
AB  - In mice depleted of B cells from birth by treatment with anti-immunoglobulin
      M(mu) antibodies, progression from a Th1- to a Th2-regulated immune response
      during primary infection with Plasmodium chabaudi chabaudi fails to occur. While
      Th1-type immunity limits parasitemia, in the absence of B cells, chronic low
      grade infections persist. Here, we show that reconstituting immune, and to a
      lesser extent naive, B cells to mice rendered deficient in B-cell function
      through anti-immunoglobulin M(mu) pretreatment restores the CD4+ T-cell response
      to the Th2 type later in P. c. chabaudi infection and with it the capacity to
      eliminate infection. This finding provides clear evidence that B cells are
      required for switching the balance of immune regulation between CD4+ T cells from
      Th1 to Th2 during P.c. chabaudi infection and supports the concept that B cells,
      through antibody production, are needed for effective antimalarial immunity.

PMID- 8557368
TI  - Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis
      of pneumonia in a neonatal mouse model of infection.
AB  - We sought to identify which Pseudomonas aeruginosa products are involved
      initiating respiratory tract infection. Defined mutants derived from strain PAO
      i.e., PAOR1 (lasR),PAO-pmm (algC) (an LPS mutant), and AK1152 (which is Fla- and
      lacks functional pili), were significantly less virulent than PAO1 in a BALBc/ByJ
      neonatal mouse model of infection as measured by their abilities to cause acute
      pneumonia, bacteremia, and death. All three mutants were also less adherent to
      epithelial cells in an in vitro binding assay. PAOR1 and AK1152 were less able to
      elicit epithelial production of interleukin-8 than PAO1. LasR was found to be
      required for the optimal expression of neuraminidase under conditions of
      increased osmolarity, as might be present in certain pathological conditions. PAO
      exsA::omega,, which lacks exoenzyme S expression, was fully virulent, causing at
      least as much pathology as PAO1. The expression of several P. aeruginosa
      virulence factors appears to be required to establish pulmonary infection in the
      neonatal mouse.

PMID- 8557369
TI  - Localization of biologically important regions on toxic shock syndrome toxin 1.
AB  - Toxic shock syndrome toxin 1 (TSST-1) contains a long central alpha helix that
      forms the base of two grooves on opposite sides of the molecule. Previous studies
      indicated that residues 132, 135, and 140 along the back of the central alpha
      helix are important in the biological activities. We made mutations of additional
      central alpha-helix residues exposed along this groove on the back of TSST-1. The
      proteins were purified, shown not to have gross alteration in structure, and
      tested for both superantigenicity and ability to elicit lethal TSS, using the
      superantigenicity, likely to because of alteration in T-cell receptor binding.
      Mutants H135A, Q136A, and E132K/ Q136K lost the ability to induce lethal TSS. The
      mutant Q136A was most increasing because it was superantigenic, yet nonlethal.

PMID- 8557370
TI  - Invasin production by Yersinia pestis is abolished by insertion of an IS200-like
      element within the inv gene.
AB  - The two enteropathogens Yersinia pseudotuberculosis and Yersinia enterocolitica
      penetrate eukaryotic cells in vitro through invasin, a surface-exposed protein.
      In contrast, Yersinia pestis, the causative agent of plague, is unable to enter
      mammalian cell lines, although the inv gene is present on its chromosome.
      Although 99.3% identical to the inv gene of Y. pseudotuberculosis, the Y. pestis
      inv gene was disrupted in its central region by a 708-bp IS200-like element.
      Multiple copies of this insertion sequence element were found within the genome
      of the plague bacillus.

PMID- 8557371
TI  - Interactions of human mannose-binding protein with lipoteichoic acids.
AB  - We explored the interaction of human recombinant mannose-binding protein and
      lipoteichoic acids (LTAs) by enzyme-linked immunosorbent assay. The best ligand
      was Micrococcus luteus lipomannan, followed by Enterococcus spp. LTA containing
      mono-, di-, and oligoglucosyl substituents. LTAs lacking terminal sugars (those
      of Streptococcus pyogenes and Staphylococcus aureus) or containing galactosyl
      substituents (those of Listeria spp. and Lactococcus spp.) were poor ligands.
      These results are consistent with known structural requirements for binding
      through the mannose-binding protein carbohydrate recognition domain.

PMID- 8557372
TI  - In vivo regulation of nitric oxide production by tumor necrosis factor alpha and
      gamma interferon, but not by interleukin-4, during blood stage malaria in mice.
AB  - We investigated whether gamma interferon (IFN-gamma; a Th1 cytokine), tumor
      necrosis factor alpha (TNF-alpha), and interleukin-4 (IL-4; a Th2 cytokine)
      modulate nitric oxide (NO) production in vivo during blood stage infection with
      Plasmodium chabaudi AS. Treatment of resistant C57BL/6 mice, which resolve
      infection with P. chabaudi AS and produce increased levels of IFN-gamma, TNF
      alpha, and NO early during infection, with anti-IFN- gamma plus anti-TNF-alpha
      monoclonal antibodies (MAbs) resulted in a reduction of both splenic inducible NO
      synthase mRNA and serum NO3- levels by 50 and 100%, respectively. Treatment with
      the anti-TNF-alpha MAb alone reduced only serum NO3- levels by 35%, and treatment
      with the anti-IFN-gamma MAb alone had no effect on NO production by these mice
      during infection. Susceptible A/J mice, which succumb to infection with P.
      chabaudi AS and produce increased levels of IL-4 but low levels of IFN-gamma, TNF
      alpha, and NO early during infection, were treated with an anti-IL-4 MAb. The
      latter treatment had no effect on NO production by this mouse strain during
      infection. In addition, our results also demonstrate that treatment of resistant
      C57BL/6 mice with anti-IFN-gamma plus anti-TNF-alpha MAbs affects, in addition to
      NO production, other traits of resistance to P. chabaudi AS malaria such as the
      peak level of parasitemia and the development of splenomegaly. Furthermore, the
      change in spleen weight was shown to be an IFN-gamma-independent effect of TNF
      alpha. Treatment of susceptible A/J mice during infection with an anti IL-4 MAb
      had no effect on these markers of resistance. Thus, these results demonstrate
      that TNF-alpha and IFN-gamma are critical in the regulation of NO production and
      other traits of resistance during P. chabaudi AS malaria in C57BL/6 mice. These
      data also indicate that treatment with an anti-IL-4 antibody alone is not able to
      induce NO production or confer resistance to A/J mice against P. chabaudi AS
      malaria.

PMID- 8557373
TI  - Immunosuppressive factor from Actinobacillus actinomycetemcomitans down regulates
      cytokine production.
AB  - A cytoplasmic soluble fraction of Actinobacillus actinomycetemcomitans Y4 was
      isolated and characterized as suppressing mitogen-stimulated proliferation of and
      cytokine production by C3H/HeN mouse splenic T cells. This factor, designated
      suppressive factor 1 (SF1), was isolated from the supernatant of sonicated whole
      bacteria and purified by Q-Sepharose Fast Flow column chromatography, DEAE
      Sepharose Fast Flow column chromatography, hydroxyapatite high-pressure liquid
      chromatography (HPLC), and Protein Pack 300 & 125 gel filtration HPLC. Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that the
      purified SF1 migrated as a single band corresponding to a molecular mass of 14
      kDa. This molecule was protease labile, heat resistant, and noncytotoxic. N'
      terminal sequence analysis revealed no homology with any known peptides of
      periodontopathic bacteria or with any host-derived growth factors. Purified SF1
      suppressed the proliferation of mouse splenic T cells which had been stimulated
      with concanavalin A, as well as suppressing the production of interleukin-2 (IL
      2), gamma interferon, IL-4, and IL-5 from CD4+ T cells as 0.1 microgram/ml or
      more. These data suggest that SF1 produced by the periodontal pathogen A.
      actinomycetemcomitans functions as a virulence factor by down regulating T-cell
      proliferation and cytokine production at local defense sites.

PMID- 8557374
TI  - Vaccination with genetically modified Shiga-like toxin IIe prevents edema disease
      in swine.
AB  - Escherichia coli strains producing Shiga-like toxin II variant (SLT-IIe, formerly
      called SLT-IIv) cause edema disease in weaned pigs. Vaccination of pigs with a
      genetically modified form of Shiga-like toxin IIe, SLT-IIe(E167Q), has been
      previously shown to be nontoxic and to induce antibodies to SLT-IIe (V.M. Gordon.
      S.C. Whipp, H.W. Moon, A.D. O'Brien, and J.E. Samuel, Infect, Immun. 60:485-502,
      1992). Fifty micrograms of SLT-IIe(E167Q) toxin was used to vaccinate suckling
      pigs at 1 and 2 weeks of age. Both vaccinated and nonvaccinated pigs were orally
      inoculated with an SLT-IIe-producing strain of E. coli after weaning (3 to 4
      weeks of age). Pigs fed a low-protein diet that were not vaccinated with SLT
      IIe(E167Q) developed subclinical edema disease, histologically evident as
      vascular necrosis. Pigs fed a high-protein diet that were not vaccinated with SLT
      IIe(E167Q) developed clinical edema disease manifested as vascular necrosis,
      reduced weight gain, ataxia, palpebral edema, lateral recumbency, and death. Pigs
      vaccinated with SLT-IIe(E167Q) had a reduction in the incidence of subclinical
      edema disease and never developed clinical edema disease. These data demonstrate
      that vaccination with a genetically modified form of SLT-IIe prevents edema
      disease and are consistent with the notion that diet influences susceptibility to
      edema disease.

PMID- 8557375
TI  - The pef fimbrial operon of Salmonella typhimurium mediates adhesion to murine
      small intestine and is necessary for fluid accumulation in the infant mouse.
AB  - We investigated the role of the pef operon, containing the genes for plasmid
      encoded (PE) fimbriae of Salmonella typhimurium, in adhesion to the murine small
      intestine. In an organ culture model, a mutant of S. typhimurium carrying a
      tetracycline resistance cassette inserted in pefC was found to be associated in
      lower numbers with murine small intestine than the wild-type. Similarly,
      heterologous expression of PE fimbriae in Escherichia coli increased the
      bacterial numbers recovered from the intestine in the organ culture model.
      Adhesion to villous intestine mediated by PE fimbriae was further demonstrated by
      binding of an E. coli strain expressing PE fimbriae to thin sections of mouse
      small intestine. The contribution of pef-mediated adhesion on fluid accumulation
      was investigated in infant mice. Intragastric injection of S. typhimurium 14028
      and SR-11 caused fluid accumulation in infant mice. In contrast, pefC mutants of
      S. typhimurium 14028 and SR-11 were negative in the infant mouse assay.
      Introduction of a plasmid containing pefBACD and orf5, the first five genes of
      the pef operon, into the pefC mutant complemented for fluid accumulation in the
      infant mouse assay. However, heterologous expression of PE fimbriae in E. coli
      did not result in fluid accumulation in the infant mouse, suggesting that factors
      other than fimbriae are involved in causing fluid accumulation.

PMID- 8557376
TI  - Effect of nitric oxide on staphylococcal killing and interactive effect with
      superoxide.
AB  - The role of reactive nitrogen intermediates (RNI) such as nitric oxide (.NO) in
      host defense against pyogenic microorganisms is unclear, and the actual
      interactive effect of RNI and reactive oxidative intermediates (ROI) for
      microbial killing has not been determined. Since, in nature, ROI and RNI might be
      generated together within any local infection, we evaluated the separate and
      interactive effects of .NO and O2- on staphylococcal survival by using a
      simplified system devoid of eukaryotic cells. These studies showed that prolonged
      exposure of staphylococci to .NO does not result in early loss of viability but
      instead is associated with a dose-related delayed loss of viability. This effect
      is abrogated by the presence of hemoglobin, providing further evidence that the
      effect is RNI associated. Superoxide-mediated killing also is dose related, but
      in contrast to RNI-mediated killing, it is rapid and occurs within 2 h of
      exposure. We further show that the interaction of .NO and O(2)- results in
      decreased O(2)--mediated staphylococcal killing at early time points. .NO,
      however, appears to enhance or stabilize microbial killing over prolonged periods
      of incubation. This study did not produce evidence of early synergism of ROI and
      RNI, but it does suggest that .NO may contribute to host defense, especially when
      ROI-mediated killing is compromised.

PMID- 8557377
TI  - Resistance to Cryptococcus neoformans is associated with an inflammatory response
      to Toxoplasma gondii in the central nervous system of mice.
AB  - We have studied the resistance of Toxoplasma gondii-infected mice to subsequent
      infection with Cryptococcus neoformans. Mice infected with the moderately
      virulent ME49 strain of T. gondii are resistant to proliferation of yeast cells
      in their brains after intravenous inoculation of the serotype A C. neoformans
      strain 184. The resistance serves to limit proliferation of yeast cells that
      colonize the brain. Maximal levels of resistance correlate not with maximal
      systemic specific anti-Toxoplasma resistance but rather with high levels of
      inflammatory response, presumably to parasites released from cysts in the brain.
      Resistance is localized, as mice infected with ME49 show only limited resistance
      in their lungs after intratracheal instillation of yeast cells, but there is
      substantial protection against development of cerebral cryptococcosis.

PMID- 8557378
TI  - Molecular characterization of a common 48-kilodalton outer membrane protein of
      Actinobacillus pleuropneumoniae.
AB  - Previous studies have shown that a vaccine prepared from outer membranes of
      Actinobacillus pleuropneumoniae serotype 5 can elicit protective immunity in
      swine against challenge with either serotype 5 or serotype 1. These results
      suggest the presence of common subcapsular surface antigens, such as outer
      membrane proteins, that contribute to cross-protective immunity. We have
      identified a 48-kDa outer membrane protein that is common to all 12 capsular
      serotypes of A. pleuropneumoniae but is not present in the outer membranes of
      related species of gram-negative swine pathogens. This protein is immunogenic in
      swine infected with either A. pleuropneumoniae serotype 5 or 1A, as well as in
      swine vaccinated with A. pleuropneumoniae serotype 5 outer membranes. This 48-kDa
      protein is readily detected in outer membranes produced by sucrose density
      gradient centrifugation, but it is sarcosyl soluble and therefore not found in
      outer membranes prepared by detergent treatment. The gene encoding the 48-kDa
      outer membrane protein has been cloned from A. pleuropneumoniae serotype 5 and
      and has been designated aopA, for Actinobacillus outer membrane protein A. The
      gene is 1,347 bp in length and encodes a protein, designated AopA, of 449 amino
      acids with a predicted molecular weight of 48,603. Southern blot analysis under
      high-stringency conditions showed that strains of all 12 serotypes of A.
      pleuropneumoniae contain DNA homologous to this gene, as do strains of two
      closely related species, Actinobacillus suis and Pasteurella multocida. Whether
      antibodies against the AopA antigen contribute to cross-protective immunity
      against A. pleuropneumoniae infection remains to be determined.

PMID- 8557380
TI  - HCV genotypes in Swedish blood donors as correlated to epidemiology, liver
      disease and hepatitis C virus antibody profile.
AB  - Sixty-two anti-HCV and HCV-RNA positive Swedish blood donors (44 men, 18 women;
      median age 34 years) were studied. HCV genotypes were correlated to parenteral
      risk factors, liver morphology, serum alanine aminotransferase (ALAT) levels and
      HCV antibody profile. Forty percent of the donors were infected with HCV genotype
      1a, 10% with 1b, 21% with 2b, and 29% with 3a. Intravenous drug use (IVDU) was
      more common in donors with genotype 3a than in those with genotype 1a (p =
      0.024), and prior blood transfusion more common in genotype 2b than in 3a (p =
      0.012). Chronic active hepatitis with and without cirrhosis was found in 38% of
      donors infected with genotype 2b as compared to 8% of donors infected with 1a (p
      = 0.034). Forty percent of donors with genotype 1a had normal ALAT at the time of
      liver biopsy versus 11% with genotype 3a (p = 0.046). Antibodies to C33c and C22
      3 were present in nearly all donors whereas reactivity to C100-3 and 5-1-1 was
      detected more often in donors with genotypes 1a and 1b as compared to donors with
      genotypes 2b and 3a. In conclusion, genotype 3a was correlated to IVDU or
      tattooing as parenteral risk factors for the acquisition of HCV infection, and
      genotype 2b to prior blood transfusion. Donors with genotypes 1a seemed to have
      less severe liver disease than those infected with genotypes 2b and 3a.

PMID- 8557381
TI  - Correlation of detectability of hepatitis C virus genome in saliva of elderly
      Japanese symptomatic HCV carriers with their hepatic function.
AB  - The hepatitis C virus (HCV) genome was sought in the saliva of 76 chronic HCV
      carriers (mean age nearly 60 years) in a rural Japanese town, who had high serum
      titers of c-100 and anti-core second generation antibodies. In 27 samples (27
      cases, 36%), the HCV-RNA genome was detected by the reverse transcriptase -
      polymerase chain reaction with either of two sets of primers covering two regions
      of the HCV genome: the 5'noncoding region and the region encompassing the
      putative envelope (E1). Transaminase values at the time of sampling were higher
      in the patients with than in those without detectable HCV RNA in saliva (p = 0.04
      for alanine aminotransferase, p = 0.04 for aspartate aminotransferase; Wilcoxon
      test). The prevalence of the positivity was higher by 5'noncoding primers (14/59
      vs. 15/68). Our data show that the severity and duration of hepatic dysfunction
      influence the detectability of the HCV genome in the saliva. This has been a
      controversial point among investigators.

PMID- 8557379
TI  - Detection and characterization by differential PCR of host eukaryotic cell genes
      differentially transcribed following uptake of intracellular bacteria.
AB  - Host eukaryotic cell genes that are differentially transcribed after phagocytosis
      of various pathogenic and nonpathogenic bacterial cells were identified by a
      differential PCR (DPCR) system. This DPCR procedure favors detection and
      isolation of host genes affected at the transcriptional level by selecting for
      poly(A) tails but differs substantially from reverse transcription-PCR. Several
      unidentified macrophage gene fragments from genes that were either
      transcriptionally activated or downregulated following uptake of Listeria
      monocytogenes into J774 mouse macrophage cells were initially defined by this
      DPCR procedure. Because of the sensitivity of the DPCR technique, all of the
      genes exhibited less than a 10-fold difference in transcription compared with
      noninfected cells as measured by limiting-dilution PCR. One of the gene fragments
      has a very high level of homology with a mitogen-activated protein kinase
      phosphatase (MKP-1), whereas the other affected fragments showed no homologies to
      known gene sequences. In addition, one of the gene fragments (WS30-B2/1) was
      specifically downregulated after L. monocytogenes uptake and another gene was
      repressed by uptake of either Shigella flexneri or L. monocytogenes, while
      transcription of the genes represented by fragment WS13-B9/9, and to some extent
      MKP-1, was activated following general phagocytosis (i.e., following uptake of
      any species of bacterium tested). Further characterization of the affected genes
      was conducted by using mutants of L. monocytogenes. A hemolysin-negative mutant
      of L. monocytogenes failed to elicit transcriptional regulation of gene fragment
      WS10-B4/14 or WS30-B2/1, and it elicited only minimal regulation of MKP-1,
      suggesting that escape from the phagosome may be required to initiate these
      responses. Furthermore, mutants with mutations in mpl and actA, two genes whose
      gene products are involved in actin polymerization and intrahost spread, also did
      not induce regulation of WS10-B4/14. These results demonstrate that (i) DPCR can
      identify specific host cell genes which are differentially transcribed after
      infection with certain microorganisms and (ii) some of these genes may be new or
      may never before have been linked to interactions between hosts and pathogens.

PMID- 8557382
TI  - Detection of neopterin, interleukin-6 and acute-phase proteins as parameters of
      potential monocyte activation in preoperative patients.
AB  - Monocytes play a key role in the immune response to trauma and infection. Is
      monocyte function already altered before surgery in terms of cell activation? On
      admission, serum neopterin was at or above 9 nmol/l in 50.2% and serum IL-6 was
      detectable (> 4 pg/ml) in 10.5% of 227 patients electively undergoing major
      abdominal surgery. Mean values of CRP (0.8 vs. 3.6), alpha-1-antitrypsin (267 vs.
      376), albumin (4.0 vs. 3.5), prealbumin (27.0 vs. 17.9, all at p < 0.01) were
      significantly different in patients with or without monocyte activation
      (neopterin > 9 nmol/l and IL-6 > 4 pg/ml). There was a significant correlation
      between neopterin and the acute phase proteins (all at p < 0.01). The data
      reflect a "primed" state at least of some parts of the immune system in a
      subgroup of preoperative patients potentially affecting their response to
      surgical trauma and bacterial contamination.

PMID- 8557383
TI  - Epidemiological survey of an outbreak of multiresistant Serratia marcescens by
      PCR-fingerprinting.
AB  - During an outbreak of Serratia marcescens from May to November 1993 43 strains
      obtained from 27 ICU patients infected or colonized with multiresistant S.
      marcescens were genotypically characterized with random amplified polymerase
      chain reaction (RAPD-PCR)-fingerprinting. In addition, 43 epidemiologically
      unrelated control isolates were selected. PCR-fingerprinting identified ten
      different genotypes of S. marcescens among the outbreak related strains. One
      predominant genotype was demonstrated in 21/43 isolates of 11/27 patients. A
      cluster of this genotype was found in seven/eight patients on the cardiosurgical
      ICU. The epidemiologically unrelated strains all showed different genotypes as
      compared to the predominant type. This survey proved RAPD-PCR to be a highly
      discriminatory and reproducible method for epidemiological studies of S.
      marcescens strains in nosocomial outbreaks.

PMID- 8557384
TI  - Predicting in-hospital outcome in HIV-associated Pneumocystis carinii pneumonia.
AB  - Pneumocystis carinii pneumonia (PCP) in HIV-infected patients remains a life
      threatening complication in the course of HIV infection. Despite effective
      treatment, mortality may still be as high as 10%. The identification of risk
      factors associated with a lethal outcome might be helpful as a guide to therapy
      for patients at risk and in the evaluation of new drugs with anti-pneumocystic
      activity. In a retrospective study 58 first episodes of HIV-associated PCP
      without prophylaxis were analyzed. Variables associated univariately with higher
      mortality were identified. A prognostic rule was established in a multivariate
      approach using canonical discriminant analysis. Cut-off values for parameters
      included were determined in order to allow a clinically applicable estimate of
      the individual risk. Variables associated with early mortality were hemoglobin,
      hematocrit, platelet count, albumin, total protein, gamma-globulins, and AaDO2.
      LDH values, percentage of neutrophils in the BAL, as well as the cellular
      immunologic state as indicated by CD4-cell count were not significantly
      associated with the outcome. The discriminant function yielded the best
      classification results with the inclusion of hemoglobin, albumin, and gamma
      globulins (overall accuracy 86%). Two or more of the following parameters were
      associated with a 14-fold increased risk of in-hospital mortality: hemoglobin
      less than 10 g/dl, albumin less than 3 g/dl, and gamma-globulins less than 1.2
      g/dl. This prognostic rule was 80% sensitive and 94% specific with a negative
      predictive value of 94%, yielding an overall accuracy of 91%. Patients with HIV
      associated PCP with a positive prognostic rule have a 14-fold increased risk for
      in-hospital lethal outcome. This discriminant rule may be helpful in identifying
      patients at risk.

PMID- 8557385
TI  - Ciprofloxacin vs. cefotaxime regimens for the treatment of intra-abdominal
      infections.
AB  - The efficacy of ciprofloxacin plus metronidazole was compared with that of
      cefotaxime plus gentamicin plus metronidazole in 79 patients with proven intra
      abdominal infections. Patients were classified with the Peritonitis Index Altona
      II (PIA-II) score for severity of disease, underlying conditions, prognosis and
      type of infection. Local peritonitis was diagnosed in 21 patients, generalized
      peritonitis in 25, intra-abdominal abscesses in 33; 35 patients had polymicrobial
      infections. Cure and improvement rates were: ciprofloxacin 77%, cefotaxime
      combination 56% (p < 0.02). Failures were significantly associated with a low
      initial PIA-II score, the presence of generalized peritonitis or abscesses,
      persistence of pathogens and superinfection. Superinfection was observed in 49%
      of the cases under cefotaxime and in 30% under ciprofloxacin. Concentrations of
      ciprofloxacin in pus ranged 2.0-5.2 mg/l with simultaneous serum concentrations
      of 1.2-3.1 mg/l.

PMID- 8557386
TI  - Management of problematic intracranial hydatid cysts.
AB  - The authors report four patients with intracranial hydatic cysts. One patient had
      a pontine lesion which was punctured and aspirated and the cyst wall removed with
      a satisfactory outcome. The second patient had multiple cysts which was
      comparable to meningeomatosis. She had a rapidly deteriorating neurologic
      condition which proved to be fatal in spite of two consecutive surgical
      interventions. The third patient had nine lesions although only six were evident
      on the MRI. All of the cysts were removed, while two cysts ruptured. Multiple
      paracardial cysts of this patient were surgically removed shortly after the
      craniotomy. The last patient, again with multiple intracranial hydatid cysts had
      safe, total removal of all cysts. The first postoperative control CT raised the
      possibility of recurrence since the CT was highly suggestive of a hydatid cyst.
      However, this was not confirmed in the follow-up CT examination. Problems and the
      solutions of management are discussed.

PMID- 8557387
TI  - Cerebrospinal fluid antiganglioside antibodies in patients with AIDS.
AB  - In this study the presence of brain antiganglioside antibodies in the
      cerebrospinal fluid (CSF) of patients with HIV infection was analysed. CSF
      samples were collected from 45 patients with AIDS and from 45 anti-HIV negative
      subjects, 15 of whom presented aseptic meningitis. Nineteen AIDS patients had
      clinically well-documented encephalopathy. Thirteen of these patients had white
      matter lesions shown by magnetic resonance imaging (MRI). Both IgG and IgM
      antiganglioside antibodies were detected by immunostaining on thin layer
      chromatography plates in three CSF samples from AIDS patients with progressive
      encephalopathy with signs of a diffuse demyelination, as revealed by MRI. Two of
      these CSF samples reacted specifically with GM3, GM1 and GD1a and one with GD1a.
      In none of the HIV infected patients without demyelinating encephalopathy, but
      with opportunistic infections or cerebral lymphoma, nor in the anti-HIV negative
      control subjects were antiganglioside antibodies detected. No association with
      JCV DNA, CMV DNA, EBV DNA, detected by nested PCR, nor HIV antigen p24 was found.
      These findings show the presence of brain antiganglioside antibodies in the CSF
      of AIDS patients for the first time. However, the findings do not suggest
      relating the presence of these antibodies to HIV encephalopathy or particular
      viral agents, but indicate that the antibodies are detectable in subjects with
      progressive encephalopathy with a diffuse demyelination.

PMID- 8557388
TI  - Influence of serum protein binding on the in vitro activity of anti-fungal
      agents.
AB  - Historically it has been assumed that the pharmacological effect is related to
      the free drug concentration. In exposing Candida albicans to itraconazole and
      ketoconazole serum concentration-time profiles, however, antifungal activity was
      not diminished despite intense albumin binding. The relevance of serum protein
      binding was further investigated, by in vitro susceptibility testing of C.
      albicans (40 clinical isolates) and Trichophyton rubrum (ten strains) against
      antifungal agents using microdilution tests allowing the determination of IC30-
      and MIC-values. The range of serum protein binding ranges from 11% with
      fluconazole to > 99% with itraconazole and terbinafine. The ratios of IC30- and
      MIC-values with and without serum protein (albumin, alpha- and gamma-globulin,
      human plasma) were related to the loss of susceptibility expected according to
      the free-drug hypothesis. A difference in the albumin effect with the test
      strains was not observed. With most antifungals including terbinafine, the
      activity declined as expected. IC30- and MIC-ratios for miconazole were 7 and 13
      (observed) vs. 12-20 (expected), for fluconazole 1.5 and 3.5 vs. 1.1, for
      amphotericin B 10 vs. 11-20, for griseofulvin 3.6 vs. 4, and for terbinafine 61
      vs. 100. Itraconazole activity, however, was not diminished by albumin (expected
      ratio 286), and ketoconazole effects decreased less than expected (ratio 5-15,
      expected about 100). alpha-globulin, but not gamma-globulin induced a major loss
      in anti-Candida activity of itraconazole and ketoconazole, which is paralleled by
      a decline in ketoconazole (but not itraconazole) activity due to plasma. With the
      other antifungals (except for ciclopiroxolamine) IC30-values for C. albicans
      increased, too. Due to the complete inhibition of T. rubrum growth by gamma
      globulin, this species proved unsuitable for studying the gamma-globulin effects.
      The present study demonstrates that the effects of intense protein binding on
      drug activity are only partly predictable from binding studies in vitro.

PMID- 8557389
TI  - Synergy of simultaneous administration of ofloxacin and granulocyte colony
      stimulating factor in killing of Escherichia coli by human neutrophils.
AB  - The in vitro effect of subinhibitory and inhibitory concentrations of ofloxacin
      and G-CSF on the bactericidal activity of polymorphonuclear leucocytes (PMNL)
      against Escherichia coli was investigated. PMNL obtained from healthy volunteers
      were incubated with different concentrations of G-CSF and ofloxacin for 180 min.
      The minimum inhibitory concentration (MIC) of ofloxacin and even 1/4 x MIC
      enhanced the bactericidal activity of PMNL. G-CSF at a concentration of 6,000
      units/ml led to a significant improvement of the bactericidal activity of PMNL.
      The combination of 6,000 units/ml of G-CSF and ofloxacin in inhibitory as well as
      subinhibitory concentrations, however, showed a significant synergistic effect on
      the antibacterial activity of PMNL during the complete incubation period.
      Combinations of G-CSF and antibiotics could therefore be beneficial for infected
      patients, especially those with impaired cellular host defense.

PMID- 8557390
TI  - First case of disseminated Mycobacterium avium infection following chemotherapy
      for childhood acute myeloid leukemia.
AB  - A 14-year-old girl of Indian origin with acute myeloid leukemia (AML) is
      presented, who was diagnosed at the age of twelve. Antileukemic chemotherapy had
      to be discontinued after 6 weeks because of persistent high fever and the
      emergence of liver and spleen abscesses. Serologic and biopsy findings were
      consistent with disseminated candidiasis; however, a liver biopsy also revealed
      granulomatous lesions with caseous degeneration. No acid-fast bacilli could be
      detected. Upon antifungal treatment the patient's condition improved, but fever
      spells and high inflammatory blood parameters persisted. One year after the
      diagnosis of AML was established, Mycobacterium avium was cultured from bone
      marrow aspirates. The patient's cellular immunity was severely compromised at
      that time as reflected by the marked depression of T-lymphocyte counts, in
      particular of CD4-positive cells. HIV and other lymphotropic virus infections
      were subsequently excluded. After 5 months of specific treatment the patient
      recovered from mycobacterial infection and remains in first remission of AML.
      Opportunistic infections have rarely been diagnosed in oncologic patients to
      date, while data on T-cell function in AML is sparse. Fever of unknown origin
      should prompt the search for infectious agents unusual to date in this patient
      group.

PMID- 8557391
TI  - Recurrence of Fusarium solani abscess formation in an otherwise healthy patient.
AB  - Fusarium spp. are usually considered opportunistic fungi in humans. A case of
      Fusarium solani abscess formation of the foot in an immunocompetent patient in
      whom recurrence occurred even after intravenous amphotericin B treatment is
      presented here.

PMID- 8557392
TI  - Acinetobacter endocarditis in children: a case report and review of the
      literature.
AB  - Acinetobacter calcoaceticus, a gram-negative bacterium ubiquitous in soil, water
      and sewage, is a rare cause of endocarditis in children. The first case of
      Acinetobacter endocarditis in an infant is described. This patient had underlying
      tetralogy of Fallot with absent pulmonary valve. A review of the literature in
      English revealed only four other cases of Acinetobacter endocarditis in children;
      three of whom had underlying congenital heart disease. Like the other reported
      cases, this patient responded well to antibiotic treatment. Subsequently this
      patient underwent corrective cardiac surgery but died of post-operative
      complications.

PMID- 8557393
TI  - Seroprevalence of hepatitis A virus antibodies in a pediatric population of
      southern Spain.

PMID- 8557394
TI  - High serum procalcitonin level in a 4-year-old liver transplant recipient with a
      disseminated candidiasis.

PMID- 8557395
TI  - Bordetella bronchiseptica pneumonia in an AIDS patient: a new opportunistic
      infection.

PMID- 8557396
TI  - Influence of control group in studies of intrafamiliar spread of hepatitis C
      virus.

PMID- 8557397
TI  - Munchhausen's syndrome in an HIV-sero-indeterminate patient.

PMID- 8557398
TI  - Comparative pharmacodynamics of clarithromycin and azithromycin against
      respiratory pathogens.
AB  - The differences between the antibacterial activities of new macrolides such as
      clarithromycin (CLA) and azithromycin (AZI) against common respiratory tract
      pathogens are only minor. However, CLA and AZI constitute macrolides with
      extremely different pharmacokinetic profiles. This constellation presents an
      opportunity to evaluate the effect of the pharmacokinetic profile on
      antibacterial kinetics comparatively. In a pharmacodynamic model simulating the
      dynamics of serum concentrations in bacterial cultures, both CLA and AZI
      demonstrate bactericidal activity at concentrations reached in human blood at
      recommended dosages (CLA 250 mg b.i.d., AZI 500 mg o.i.d.). Bactericidal activity
      of CLA against the variety of pathogens included is superior to that of AZI in
      the rate and the extent of killing in this model. These results are considered to
      correlate with the antibacterial effect of macrolides in vivo in cases where
      pathogens enter the blood stream. Furthermore, mutants with susceptibility
      reduced between 8 and 16 times in relation to the initial strain of all strains
      having an initial minimal inhibitory concentration (MIC) < or = 0.25 mg/l, are
      selected during exposure to AZI, but not to CLA. The pharmacokinetic profiles of
      CLA and AZI thus strongly influence their antibacterial effect in the
      pharmacodynamic model, allowing both higher bactericidal activity and greater
      reduction of the risk of selection of resistant mutants with CLA than with AZI.
      As a whole, the pharmacodynamics of these macrolides are determined more by the
      proportion of the MICs to the maximum serum concentration than by the relation of
      the MICs to the area under the curve.

PMID- 8557399
TI  - Multicentre study for diagnostic evaluation of an assay for simultaneous
      detection of antibodies to HIV-1, HIV-2 and HIV-1 subtype 0 (HIV-0).
AB  - The aim of the study was to evaluate a new ELISA for detection of HIV-1, HIV-2
      and HIV-1 subtype 0 (HIV-0) antibodies. The assay format is based on the antigen
      sandwich principle. To enable specific detection of HIV-0 antibodies, in addition
      to HIV-1 and HIV-2 antigens HIV-0 antigen is used for coating the solid phase and
      for the conjugate. The results show that all 12 HIV-0 samples tested were
      detected with a high degree of reactivity, as were all the 1,144 anti-HIV-1 and
      424 anti-HIV-2 positive samples. The capacity of the test to enable early
      detection of seroconversions is equivalent to that of other sandwich ELISAs. The
      specificity of the assay was determined to be 99.89/99.94% (initial/after retest)
      using 58,366 samples, which is superior to the other ELISAs used for comparison.
      Even with difficult samples (i.e. samples of African origin, samples known to
      cause false-positive reactivity in different ELISAs, or samples containing
      potential interference factors) there were very few false-positive reactions.
      Therefore, the new assay is well suited for screening blood donations as well as
      for evaluating samples from patients of different geographic origin.

PMID- 8557400
TI  - Safety and immunogenicity of an inactivated hepatitis A vaccine in children 2 to
      5 years old.
AB  - The reactogenicity and immunogenicity of an inactivated hepatitis A vaccine were
      assessed. Seventy healthy children aged between 2 and 5 years old, who lacked
      antibodies against the hepatitis A virus, were enrolled in this study. With a 0-,
      1-, and 6-month vaccination schedule, the children received three doses of 360
      enzyme-linked immunosorbent assay (ELISA) units of hepatitis A vaccine
      intramuscularly (deltoid). Safety parameters were recorded in standardized diary
      cards by the parents on the day of injection and the three following days. Blood
      tests for liver enzymes and anti-hepatitis A virus antibody analyses were
      performed the day of screening and 1, 2, 6 and 7 months after the first dose.
      Anti-hepatitis A virus antibody was tested by ELISA. Titres < 20 mIU/ml were
      considered negative. For the three hepatitis A vaccine doses administered, 22%
      (46/210) of the diary cards reported any kinds of signs or symptoms. Soreness at
      the injection site (9%, 18/210) and malaise (6%, 12/210) were the most common
      local and systemic reactions reported, respectively. The seroconversion rates
      were 83, 99 and 100% one month after the 1st, 2nd, and 3rd doses, respectively.
      The corresponding geometric mean titres were 124, 352, and 2,778 mIU/ml. We
      conclude that this HAV vaccine is safe and immunogenic in healthy children. As
      the hepatitis A epidemiology pattern is rapidly changing in our country (and
      other regions), resulting in an increasing population of susceptible adolescents
      and young adults, we suggest that the routine vaccination against hepatitis A in
      pre-school children attending day-care centres should be seriously considered.

PMID- 8557401
TI  - Utilization of laboratory resources: developments in knowledge-based ordering
      systems.
AB  - This paper describes two rule based decision support systems. The first system is
      used to screen incoming test requests for adequacy on the basis of signs and
      symptoms volunteered by the requesting GPs. The system was tested using a
      database of 794 requests for a TSH test. About 17% of the test requests were
      correctly identified as unnecessary. In total, 0.5% of the tests were incorrectly
      labelled as unnecessary. This concerned 4% of the patients that appeared to have
      hyperthyroidism and 23% of the patients that appeared to have hypothyroidism on
      the basis of TSH and FT4 results. The other system is a rule-based clinical
      decision support system for the requesting of laboratory investigations,
      originally designed for use at a hospital within the UK, that was implemented in
      a predominantly French-speaking hospital in Belgium. This involved the
      modification of the system to allow multilingual operation, and also the
      implementation of a completely new set of investigation protocols. The purpose of
      this study was to assess the transferability, both of the system itself, and of
      its benefits. The system was introduced gradually and has only recently been in
      full operation. However, the findings from the first months of routine use of the
      system indicate that the transfer of the system to a different clinical
      environment has been successful. Although it is too early to assess fully the
      impact on laboratory utilization, the clinicians believe that it is improving the
      appropriateness of investigations.

PMID- 8557402
TI  - Choice of antibiotics by the site of infection in a community hospital.
AB  - A total of 1578 culture and antimicrobial susceptibility results on clinical
      specimens from various sites of infection were analyzed, by using the software
      installed in the MicroScan System of an automated microbiology analyzer, and by
      mathematical calculation. A list of antimicrobial drugs of choice by the site of
      infection is determined on the basis of the computer and mathematical analysis of
      the above data. The list suggested in this in vitro study may be useful to
      clinicians for selection of an initial antimicrobial agent in hospitals or
      communities when an infection is suspected in a site of infection before the
      results of cultures and antimicrobial susceptibility tests are reported. This
      list may also be helpful for initial therapy in critically ill patients before
      ordering culture and susceptibility testing, as well as for preoperative
      prophylaxis.

PMID- 8557403
TI  - A computerized procedure for developing and administering time perception
      protocols: application to a sample of adults and adolescents.
AB  - The principal goals of this work are: (a) To describe an integrated computerized
      procedure for designing, administering, and recording time perception experiments
      (more specifically, reaction time and time estimation) on human subjects; (b) To
      present the results of applying this procedure to the study of fourteen normal
      adolescents and fourteen normal adults. Individualized time perception protocols
      can be designed with this menu-driven highly interactive computer-program. Such
      protocols can then be used for testing experimental subjects. The programs run on
      any IBM-compatible computer, and the resulting test data are stored in ASCII
      format. As an example of the use of this procedure, reaction time with five
      regular and irregular preparatory intervals (PIs), and time estimation of 10 s
      with and without feedback was measured on normal adolescents and adults. For
      short PIs the adolescents had reaction times (RTs) similar to adults, but
      significant longer RTs than adults for long PIs. In the case of time estimation
      no differences between the two groups were observed; however, both groups
      underestimated time when no feedback was provided; that is, they thought that
      less time had elapsed than really had.

PMID- 8557404
TI  - Computer model of human lung morphology to complement SPECT analyses.
AB  - Aerosol therapy protocols could be improved if inhaled pharmacologic drugs were
      selectively deposited within the human lung. The targeted delivery to specific
      sites, such as receptors and sensitive airway cells, would enhance the efficacies
      of airborne pharmaceuticals. The high spatial discrimination of deposition
      patterns of inhaled particles can be determined via Single Photon Emission
      Computer Tomography (SPECT). However, major problems continue to compromise SPECT
      protocols. Our work focuses on two issues: how can the spatial discrimination be
      improved; and how are the images to be interpreted? We present a methodology,
      described by a mathematical model and supercomputer code, for systematically
      slicing through the human lung in a prescribed manner that is conducive to
      implementation into SPECT analyses. The lung is divided into concentric shells,
      or annuli, and the airway generation-by-generation composition of the respective
      shells determined. This identification was accomplished by superimposing the new
      shell structure with the 3-D branching network presented by Martonen et al. [23].
      Perhaps the key aspect of the model-code is that the supercomputer is instructed
      to determine the 3-D spatial coordinates of each of the airways (over 16 million)
      of the lung with respect to the clinician-selected contours of shells within the
      lung.

PMID- 8557405
TI  - An iterative approach on magnetic source imaging within the human cortex--a
      simulation study.
AB  - A simulation study on magnetic source imaging within the human brain from a
      synthetic evoked magnetic field is presented. An inhomogeneous boundary element
      (BE) head model (cortex cerebrospinal fluid) was built up from real magnetic
      resonance imaging (MRI) cross-sections. In the forward problem, one or two
      rotating primary current dipoles (PCDs) are located at arbitrary sites within the
      auditory cortices. The PCDs should represent focal and distributed neural
      activities, respectively. The reconstruction space (predefined by a priori
      morphological information) is defined as a surface within the three-dimensional
      cortical volume, with an averaged distance of 0.005 m to the outer cortex
      surface. The reconstructed pseudo primary current dipoles (PPCDs) are not
      restricted to any particular direction. The observation space consists of two
      concave surfaces closely above the scalp. Each observation surface contains 37
      observation points. An iterative Wiener filter estimation (WFE) is applied in
      order to reconstruct PPCD distribution from simulated magnetic field data. This
      iterative WFE approach enables the simultaneous localization of focal and
      distributed activities. Aspects on the correlation between neural activities are
      not investigated within this paper.

PMID- 8557406
TI  - A polygon matching algorithm and its applications to verification of radiation
      field placement in radiotherapy.
AB  - An automated method for quantitative evaluation of geometric accuracy of
      radiation field placement during radiation therapy treatments has been developed
      and is presented in this article. The method is based on matching polygons
      representing the boundaries of the prescribed and treated radiation fields. An
      efficient algorithm for finding the intersection of two arbitrary simple polygons
      has been developed for that purpose. The process of polygon matching is performed
      by iterative optimization of the goodness-of-match measure derived from the area
      of the intersection between the two polygons to be matched. The optimization is
      done with respect to the translation and rotation in the plane that are applied
      to the polygon representing the treated field. The optimum translation and
      rotation define the adjustments in the position of the treated field, relative to
      the patients anatomy, which are necessary in order to bring the treated field
      into the best possible agreement with the prescription. The radiation field
      matching scheme was applied to a clinical dataset consisting of prescription
      treatment field pairs extracted from simulation and portal images for 40
      patients. It is concluded that the observed accuracy and efficiency of the method
      make it very suitable for applications in radiation therapy verification.

PMID- 8557407
TI  - Renal function tests for windows--a model for the development and distribution of
      medical software on the Internet.
AB  - A computer application (Renal Function Tests for Windows) was developed to
      calculate and sort data for quantitative renal function testing using the
      Microsoft Visual Basic for Windows programming language. The following diagnostic
      indices are computed: Measured creatinine clearance--The rate at which serum is
      cleared of creatinine. Standardized clearance--Creatinine clearance scaled by
      body surface area. Estimated creatinine clearance--Renal creatinine clearance
      estimated from serum creatinine Renal failure index--To distinguish prerenal
      azotemia from oliguric acute renal failure. Renal free water clearance--Net
      volume per min of free water excreted by the kidneys. Fractional excretion of
      filtered sodium--To distinguish prerenal azotemia from acute renal failure. Renal
      Function Tests for Windows (RFT) allows the user to choose to enter only the data
      that is available. The program will then calculate all the possible results from
      the given data. Upon request, the program will also inform the user of data that
      is missing for those results that cannot be calculated. The flexibility of this
      program allows the user to perform 'what if' analysis through the manipulation of
      input data. Distribution of this program was accomplished using the Internet File
      Transfer Protocol (FTP) service. The effectiveness of mode of distributing
      medical software awaits feedback from users on the Internet.

PMID- 8557408
TI  - Interpretations of risk: the use of scientific information in the development of
      the alcohol warning label policy.
AB  - In 1988 the US Congress passed a law requiring a health warning label on
      alcoholic beverage containers, to include the message that pregnant women should
      not drink alcohol. This paper addresses the role that scientific knowledge played
      in the formation and passage of the alcohol warning label policy. The
      constellation of birth defects implicated in the fetal alcohol syndrome (FAS)
      (including fetal alcohol effects) is sketched, and the FAS-related legislative
      events leading to the law's passage are described. A synopsis of the state of
      knowledge in 1988 regarding the effects of alcohol on the fetus is presented, and
      a snapshot of the social climate at that time is offered. The paper concludes
      with an update of relevant FAS research since the legislation was passed, and
      considers implications for future research and policy in the prevention of FAS.

PMID- 8557409
TI  - A multiple-level, comprehensive approach to the prevention of fetal alcohol
      syndrome (FAS) and other alcohol-related birth defects (ARBD).
AB  - A comprehensive program for the prevention of fetal alcohol syndrome (FAS) and
      alcohol-related birth defects (ARBD) must consider multiple approaches and
      utilize knowledge from a variety of academic disciplines. Issues related to
      culture, society, behavior, belief systems, and medicine must all be considered
      for both etiology and solutions. A broad paradigm such as a public health model
      integrates various elements of approach. Because FAS and other levels of ARBD
      form a spectrum, from severe to negligible damage, a variety of drinking patterns
      with various characteristics and etiologies have to be addressed. This paper
      describes a multiple-level, comprehensive program with primary, secondary, and
      tertiary prevention components. Practical recommendations are proposed for
      addressing ARBD in a variety of arenas. While secondary and tertiary prevention
      hold promise for short-term reduction of FAS and ARBD prevalence, comprehensive
      prevention serves both short- and long-term effects. Multiple level prevention
      efforts are well served by clear and compelling vision and mission statements,
      and require careful evaluation.

PMID- 8557410
TI  - Therapeutic communities for addictions: a theoretical framework.
AB  - Adaptation of therapeutic communities (TCs) for new clients and in different
      settings has resulted in a diversity of programs with unique treatment protocols
      and different planned duration of stays. The extent to which the various
      adaptations retain the essential elements of the TC model is not known, and
      moreover, casts questions about the general effectiveness of the therapeutic
      community modality. This paper outlines a theoretical framework of the addiction
      TC to advance research and guide training, practice, and program development. The
      essential elements of the TC are organized into four areas: its perspective,
      treatment approach, program model, and the treatment process. Some implications
      of a TC theory, model, and method are discussed in terms of research, treatment,
      and policy issues.

PMID- 8557411
TI  - Syringe exchange: HIV prevention, key findings, and future directions.
AB  - HIV among injecting drug users (IDUs) has now been documented in over 60
      countries in the world, and there are an additional 40 countries where injecting
      drug use has been reported including widespread epidemics in Southeast and
      southern Asia and in Latin America. At present HIV infection is almost always
      fatal, and there is no promise that a preventive vaccine will become available
      soon. Given the enormity of the HIV epidemic among IDUs and the critical need to
      reduce the spread of HIV transmission to and from IDUs, prevention efforts are
      essential. Syringe-exchange programs have become a major component of HIV
      prevention strategies in most developed countries and work within the philosophy
      of harm reduction. Increasing access to sterile syringes has been met with
      considerable controversy. Opponents of syringe exchange have generally argued
      that increasing access to sterile syringes would simultaneously increase the
      number of injecting drug users, increase the frequency of injection for already
      active IDUs, and appear to "condone" an illegal behavior. To date many research
      studies and four major reviews of syringe exchange literature have been
      conducted. All studies thus far have shown no increase in illicit drug injection
      associated with syringe exchanges, and significant decrease in drug risk
      behaviors.

PMID- 8557412
TI  - [Traumatic luxation of the peroneal tendons. Report of 36 cases].
AB  - Between January 1970 and September 1992 we operated on 35 patients with
      dislocation of the peroneal tendons; in 1 patient both sides were affected.
      Twelve cases were acute and 24 chronic; 83% were due to injuries at sport, 90% of
      which were in downhill skiers. In 25 cases the fibroperiosteal detachment and the
      lax tendon sheath were repaired using either the technique of Meary, or that
      devised by ourselves. Exner suture of the lesion of the main body of the sheath
      was carried out in 8 cases, and other procedures in the remainder. Ninety two
      percent of patients had a satisfactory result. The surgical procedure adopted
      must depend on the patterns of injury, but the majority of cases require
      fibroperiosteal release with transosseus reattachment of the sheath.

PMID- 8557413
TI  - The cervical spine in the Klippel-Feil syndrome. A report of 57 cases.
AB  - We report 57 cases of the Klippel-Feil syndrome. Five had type I congenital
      cervical fusion, 48 type II and 4 type III. The symptoms and signs varied
      considerably. Patients with C2-C3 fusion often had symptoms associated with
      odontoid dysplasia and occipito-cervical instability. Twenty-one had progressive
      neurological symptoms and 19 were operated on: 3 had occiput-C3 posterior
      arthrodeses, 2 a single level fusion, 1 a laminectomy and anterior arthrodesis,
      and 13 had laminoplasties. Degenerative changes at the unfused segment and a
      narrow bony canal are high risk factors in the development of neurological
      compromise.

PMID- 8557414
TI  - The anatomy of de Quervain's disease. A study of operative findings.
AB  - We have studied the anatomical findings at operation on 67 patients with De
      Quervain's disease, 5% of whom had bilateral lesions, compared with published
      series of cadaveric dissections. There was division with a septum in the extensor
      compartment in 60%. The abductor pollicis longus had more than one tendon in 76%
      and extensor pollicis brevis was represented by a single tendon in 96%. If there
      was an anatomical predisposition to the condition, more cases would have been
      bilateral. A septum and a crowded compartment are mainly responsible for the
      failure of steroid injections.

PMID- 8557415
TI  - The fixation of porous-coated femoral stems. A radiographic study of 113 cases
      with a 4 to 8 year follow up.
AB  - Changes occurring in the fixation of 113 porous-coated PCA uncemented femoral
      stems were studied in 90 patients who were operated on between 1984 and 1988. The
      average follow up was 5 years. Fixation was classified in radiographs as
      osteointegration, stable fibrous fixation or unstable. Four femoral components
      were revised. Metaphyseal osteoporosis was associated with those with a stem
      diameter greater than 13 mm. After 2 years, osteointegration was present in 73%
      and instability in 24% which was not related to the position of the stem. At the
      end of the follow up period, 20% of the stems showing osteointegration had
      changed and become unstable.

PMID- 8557416
TI  - External fixation of intertrochanteric fractures of the femur.
AB  - Forty patients with intertrochanteric fractures of the femur were treated by
      external fixation between July 1992 and April 1994. They were selected because of
      their high surgical risk, and evaluated by radiographs immediately after
      operation, and at 30 and 90 days. The results indicate that external fixation is
      a useful method of treatment for this type of patient.

PMID- 8557417
TI  - Surgical correction of idiopathic medical femoral torsion.
AB  - We reviewed 28 hips in 14 patients with severe bilateral idiopathic medial
      femoral torsion which had been corrected by intertrochanteric rotation osteotomy
      using crossed pins for fixation and a hip spica. There were 10 girls and 4 boys
      with a mean age of 7 years and 9 months. All had functional and cosmetic
      disability before operation. The average follow up was for 3 years and 9 months.
      Full correction was achieved in 27 hips. In one partial avascular necrosis of the
      femoral head occurred one year after operation and was treated by an acetabular
      augmentation procedure with a satisfactory outcome.

PMID- 8557418
TI  - The influence of the position of the patellar component on tracking in total knee
      arthroplasty.
AB  - The position of the patellar component and patellofemoral symptoms were assessed
      in a series of 72 cemented polyethylene patellar components in total condylar
      arthroplasties. A small (25 mm) component was used. The minimum follow up was 2
      years and maximum 3 years. A lateral retinacular release was carried out in 22
      knees. Clinical results were assessed by questionnaire and 86% had no
      patellofemoral symptoms. The mean postoperative patellar height was not changed
      compared to the preoperative height. Lateral placement of the patellar component
      was associated with both increased medial tilt and lateral subluxation. The
      component should be inserted so that its centre is slightly medial to the centre
      of the bone.

PMID- 8557419
TI  - Evaluation of anterior cruciate reconstruction reinforced by the Kennedy ligament
      augmentation device. An arthroscopic and histological study.
AB  - Fifty anterior cruciate ligament reconstructions with the Kennedy ligament
      augmentation device were examined arthroscopically and histologically 6 to 61
      months after operation. The autogenous segments used were the quadriceps tendon
      in 13 and the semitendinosus tendon, with or without gracilis, in 37. The
      arthroscopic findings were rated as good in 31, fair in 15 and poor in 4, and
      there was correlation between these grades and KT-1000 measurements. The
      histological findings were graded as good in 17, fair in 26 and poor in 4; these
      did not correlate with the arthroscopic grades but with the time interval after
      reconstruction. Maturation of the autogenous augmented segment was found to
      progress with time, but took more than 3 years to become complete.

PMID- 8557420
TI  - Evaluation of joint thickness in the hip before and after osteotomy using three
      dimensional modelling.
AB  - Joint thickness was assessed using three-dimensional modelling techniques before
      and after the Bombelli intertrochanteric valgus-extension osteotomy. Before
      operation, the average thickness of the entire hemispherical surface was 2.3 mm,
      which was significantly thinner than that of the controls. After operation, 11 of
      12 patients showed an average increase in thickness to 3 mm, nearly equal to that
      of the controls, and this was accompanied by clinical improvement.

PMID- 8557421
TI  - Incorporation of diaphyseal sequestra in chronic haematogenous osteomyelitis.
AB  - Seventeen patients with haematogenous osteomyelitis and long diaphyseal sequestra
      are reported. Treatment was incision and drainage with antibiotics for at least 6
      to 8 weeks, the limb being protected in plaster for a long time. The sequestra
      became incorporated in every case. Sequestrectomy should only be undertaken when
      successive radiographs show no reduction in size of the sequestrum and an
      increase in the amount of the involucrum.

PMID- 8557422
TI  - Proximal radio-ulnar synostosis treated by interpositional silicone arthroplasty.
      A case report.
AB  - A case of post-traumatic proximal radio-ulnar synostosis in a young adult is
      described. Treatment was by excision of 1 cm of the shaft just below the
      synostosis and interposition of a radial head silicone implant. The functional
      result was excellent after 10 years.

PMID- 8557423
TI  - Slipped capital femoral epiphysis associated with hyperparathyroidism. A case
      report.
AB  - A case of slipped capital femoral epiphyses is reported which occurred in
      association with primary hyperparathyroidism. Only two similar cases have been
      found in the English literature. The patient was a man, 16 years of age, who
      presented with bilateral slipped epiphyses. Investigation showed that he had
      primary hyperparathyroidism due to a parathyroid adenoma. At a single operation,
      the epiphyses were pinned in situ, and the adenoma removed. The result was
      satisfactory.

PMID- 8557424
TI  - Pseudoaneurysm of the brachial artery caused by an osteochondroma. A report of
      two cases.
AB  - We present two cases of osteochondroma associated with a pseudoaneurysm of the
      brachial artery. The diagnosis was confirmed by arteriography and ultrasonography
      in one case. Treatment was resection of the pseudoaneurysm, and saphenous vein
      grafting, with excision of the osteochondroma in both patients.

PMID- 8557425
TI  - Extraskeletal osteosarcoma with a highly malignant course. A case report.
AB  - A case of a highly malignant extraskeletal osteosarcoma is reported. Although
      biopsy is not considered necessary in cases of heterotopic calcification when the
      aetiology is known, malignancy should be suspected when the cause is
      questionable.

PMID- 8557426
TI  - The haemophilic pseudotumour.
AB  - The orthopaedic management of severe haemophilia is mainly concerned with intra
      articular and intramuscular bleeding. Pseudotumour is a serious, but very rare,
      complication; it is a progressive cystic swelling involving muscle, produced by
      recurrent bleeding and accompanied by radiographic evidence of bone involvement.
      Ultrasonography, CT scan, MRI and vascular injection studies should be
      undertaken, but preoperative biopsy is contraindicated. Most pseudotumours are
      seen in adults and occur near the large bones of the proximal skeleton. However,
      a number develop distal to the wrist and ankle in younger patients before
      skeletal maturity. If untreated, proximal pseudotumours will destroy soft
      tissues, erode bone and produce vascular or neurological lesions. Surgical
      removal is the treatment of choice when it can be carried out in major
      haemophilia centres, and has a mortality rate of 20%. Regression, but not a true
      cure, may occur with long term replacement therapy and immobilisation; this
      conservative treatment is not recommended except in patients with high-titre
      inhibitors in whom operation is not a possibility. In these cases, percutaneous
      evacuation and filling with a fibrin seal or cancellous bone, depending on the
      size of the cavity, should be carried out. Distal pseudotumours should be treated
      primarily with long term factor replacement and cast immobilisation because they
      may respond to many modalities of conservative management. The presence of one or
      more progressively enlarging masses in the limbs or pelvis of a haemophiliac
      should raise the suspicion of a pseudotumour, although chondrosarcoma and
      liposarcoma have occurred in such patients.

PMID- 8557427
TI  - Access to equipment which allows scanning and digitalization of radiographs.

PMID- 8557428
TI  - Paradigms, pre-emptions, and stages: understanding the transformation of American
      psychiatry by managed care.

PMID- 8557429
TI  - The overuse of criminal justice dispositions: failure of diversionary policies in
      the management of mental health problems.

PMID- 8557430
TI  - Moral state of reasoning and the misperceived "duty" to report past crimes
      (misprision).

PMID- 8557431
TI  - The expert deposes, but the court disposes: the concept of malingering and the
      function of a medical expert witness in the forensic process.

PMID- 8557432
TI  - Sources of variability in prevalence rates of Alzheimer's disease.
AB  - OBJECTIVE: To investigate potential methodological reasons for the differences in
      published Alzheimer's disease (AD) prevalence rates. BACKGROUND: Studies
      reporting prevalence rates of AD have been published worldwide. These rates
      differ considerably, but may greatly reflect methodological differences. METHODS:
      All studies published between 1984 and 1993 that reported age-specific AD rates
      and sample sizes were included. Logistic regression identified variables that
      contribute to the variation in rates. Estimates of extrabinomial variation were
      also calculated. RESULTS: Studies characterized by the following features yielded
      significantly higher rates: inclusion of mild cases, use of laboratory studies,
      ascertainment of a sample rather than the total population, inclusion of both
      urban and rural populations, non-use of computerized tomography (CT) scans, non
      use of the Hachinski Ischemic Score, and no adjustment for false negatives. The
      odds of having AD increased 18% for every year of age. The variation in the age
      specific prevalence rates of AD was approximately 15 times that expected by
      sampling variation. However, approximately 76% of this excess variation in rates
      could be accounted for by methodological differences. CONCLUSIONS: After
      accounting for age, much of the variability in prevalence rates of AD in the
      published literature may be explained by differences in methodology. Some
      unexplained variation in prevalence rates, however, still remains.

PMID- 8557433
TI  - Use of traditional and orthodox health services in urban Zimbabwe.
AB  - BACKGROUND: Health care in Zimbabwe is provided by both orthodox and traditional
      care providers. With formal medical services under economic strain it is
      important to understand the extent of consulting with traditional care providers
      and their effectiveness. METHODS: A cross-sectional community survey recorded
      consultations and self-treatment for episodes of illness among 1251 individuals
      in 222 households randomly selected in two high-density suburbs of Harare,
      Zimbabwe. Three dependent variables (illness experience, consultation behaviour
      and choice of care provider) were analysed against a range of sociodemographic,
      episode-related and outcome measures. RESULTS: More than one-third of the sample
      had experienced an illness and 83% of these had led to consultation. Medical
      services were consulted eight times more often than traditional ones. Non
      consulting behaviour was associated with lack of money or low perceived
      significance of problems. Physical problems were usually taken to medical clinics
      where their outcome was better, but non-specific pain and other problems did no
      better with medical or traditional care. CONCLUSIONS: While members of the
      community appear to recognize physical problems and take them to medical care,
      traditional and orthodox medical consultations appear to be equally effective for
      non-specific pain or non-specific physical problems. The role of traditional
      medicine in relation to non-specific physical problems and psychological problems
      is one which deserves further examination from both clinical and administrative
      perspectives. Poverty appears to be associated with poorer outcomes; this is a
      potentially important issue in times of increasing economic hardship.

PMID- 8557434
TI  - Epidemiological measures of participation in community health promotion projects.
AB  - BACKGROUND: The paper is concerned with the use of epidemiological methods to
      measure the rates at which different strata of a defined population participate
      in community health promotion projects. The specific aim was to estimate the
      incidence rates of participation in projects sponsored by the Western Australian
      Health Promotion Foundation (Healthway), separately for sociodemographic and
      health-related behavioural subgroups. METHODS: Data were drawn from Healthway
      sponsorship projects in 1992. Each sport, arts and racing project was associated
      with promotion of a health message and creation of a health promoting
      environment. The study used a two-stage sampling design. Thirteen of 57 large
      sponsorship projects and 30 of 129 small projects were selected. In the second
      stage, respondents were randomly surveyed from among project participants. A
      total of 4060 respondents aged > or = 10 years was sampled from the 43 selected
      projects. Population-based incident participants were estimated and were related
      to person-years at risk. RESULTS: The total participation rate was 4.01 per
      person-year. The rate was very high at ages 10-14 years and thereafter declined
      with increasing age. Compared with the least socially disadvantaged 25% of
      population, the participation rate fell by around one-third in the medium and
      high disadvantage groups, but exceeded the baseline by a ratio of 1.85 (95%
      confidence interval: 1.57-2.18) in the most disadvantaged 10% of population. The
      effect was most pronounced at ages 10-19 years. Participation was higher in those
      who smoked, drank alcohol unsafely, reported sunburn and reported low consumption
      of fruit and vegetables. However, participation was reduced in people who were
      sedentary. CONCLUSIONS: Epidemiological methods can be used to evaluate the
      distribution of participation of a population in community health promotion
      projects. The Western Australian Health Promotion Foundation has been successful
      in reaching disadvantaged youth.

PMID- 8557435
TI  - The effect of human immunodeficiency virus infection on birthweight, and infant
      and child mortality in urban Malawi.
AB  - BACKGROUND: Low birthweight, prematurity and intra-uterine growth retardation
      (IUGR) are major determinants of child survival. Therefore, it is important to
      assess excess mortality due to human immunodeficiency virus (HIV) infection in
      populations where low birthweight is common. METHODS: A prospective study was
      conducted on 1385 children born to seropositive and seronegative women in urban
      Malawi. Children were regularly examined and tested for HIV. RESULTS: The
      mortality rate of children of HIV seropositive mothers was substantially higher
      (223/1000 at 12 months, 317/1000 at 24 months and 360/1000 at 30 months) than
      that of children of seronegative mothers (68/1000 at 12 months, 106/1000 at 24
      months and 118/1000 at 30 months). The incidence of prematurity and IUGR was also
      higher in infants of HIV seropositive mothers than in infants of seronegative
      mothers (12.7% versus 3.8%, P < 0.001 for premature and 7.7% versus 4.4%, P =
      0.02 for IUGR infants). The mother-to-infant HIV-1 transmission rate was 35.1%.
      After 12 months of age, HIV infected children showed the highest mortality;
      however, uninfected children of HIV seropositive and children of HIV seronegative
      mothers had similar mortality. The mean birthweight of HIV infected and
      uninfected children was not significantly different. In HIV infected children the
      most frequent causes of death were diarrhoea, pneumonia and failure to thrive.
      Less common risk factors for child mortality included active maternal syphilis
      and cervicitis/vaginitis. CONCLUSION: The substantial difference in survival
      among children of HIV infected and uninfected mothers suggests that mortality
      could be reduced if HIV infection were not a risk factor. To decrease childhood
      mortality, a combination of interventions such as treatment of sexually
      transmitted infections during pregnancy and measures to reduce mother-to-infant
      transmission should be adopted.

PMID- 8557436
TI  - Prevalence of HIV-1 infection in 18 year old men in Tuscany. The Toscana
      Collaborative Group.
AB  - BACKGROUND: The main route of transmission of the human immunodeficiency virus
      type 1 (HIV-1) is sexual contact. A high proportion of young adults is exposed to
      this mode of transmission. Therefore it is important to assess the level of HIV-1
      prevalence among 18 year olds in Italy. METHODS: Available blood samples taken at
      the physical examination of the military draft visit in Tuscany, Italy, have been
      tested in an anonymous unlinked fashion for HIV-1 infection in 1990 and 1991.
      RESULTS: In the 2 years, 4478 and 4959 men were tested, respectively,
      representing 91.7% of all subjects included in the draft lists. Prevalence of HIV
      1 infection was 1.12 per 1000 (95%CI: 0.36-2.61 per 1000) in 1990 and 0.20 per
      1000 (95% CI: 0.01-1.12) in 1991. CONCLUSIONS: Prevalence of HIV-1 infection in
      the 18 year old male population in Tuscany is close to or below 1/1000. Evidence
      of the presence of HIV-1 infection in this population should prompt the
      implementation of adequate prevention programmes among adolescents.

PMID- 8557437
TI  - Validity of self-reported sexually transmitted diseases in a cohort of drug-using
      prostitutes in Amsterdam: trends from 1986 to 1992.
AB  - BACKGROUND: Rates of self-reported sexually transmitted diseases (STD) among drug
      using prostitutes in Amsterdam have been shown to be declining. However, self
      reports may provide biased estimates. METHODS: We determined the prevalence of
      risk indicators for and time trends in incorrect self-reported STD in a cohort of
      drug-using prostitutes. Rates of self-reported STD were validated with diagnosed
      STD from a special STD clinic for drug-using prostitutes. RESULTS: Between 1986
      and 1992, 314 STD were diagnosed in 85 (65%) of 131 studied prostitutes. Overall,
      34% of diagnosed STD was not reported in the cohort, referred to as
      underreporting. For 40% of reported STD, no diagnosis was obtained
      ('overreporting'). In spite of these misclassifications, absolute numbers of
      reported and diagnosed STD practically balanced. Underreporting was independently
      associated with longer residence in Amsterdam (OR = 2.34 per 5 years), more than
      six clinic visits between two cohort visits (OR = 0.31), daily use of non
      parenteral drug (OR = 8.45) and mainly injecting heroin (OR = 6.93);
      overreporting was independently associated only with a lower frequency of clinic
      visits. Multivariate analyses showed that trends in underreporting and
      overreporting were in part explained by a higher number of visits in the cohort
      and by lower numbers of clinic visits between two cohort visits. CONCLUSIONS:
      Self-reporting of STD in our cohort is unreliable and misclassification
      prevalent; risk factors for and associates of self-reported STD are biased.
      Inferences drawn from self reports are potentially misleading and therefore such
      data need to be validated. Trends in misclassification can be interpreted as
      recall errors and as a study participation effect. For monitoring of STD
      prevalences in relation to trends in sexual risk behaviours, diagnosed STD should
      be used in preference to self reports.

PMID- 8557438
TI  - Efficacy of BCG vaccination of the newborn: evaluation by a follow-up study of
      contacts in Bangui.
AB  - BACKGROUND: The efficacy of Bacillus of Calmette and Guerin (BCG) vaccination
      given at birth is still controversial. We therefore conducted a study in Bangui
      (Central African Republic) to estimate the protection afforded over the first
      seven years of life by BCG administered at birth. METHODS: One thousand children
      who had lived in contact with a recently diagnosed case of contagious
      tuberculosis were followed up for a period of 6 months in order to detect the
      occurrence of tuberculosis. Diagnosis of tuberculosis was made through a scoring
      system. Vaccine efficacy (VE) was calculated on the basis of the relative risk of
      contracting tuberculosis according to vaccination status. RESULTS: The efficacy
      of BCG was estimated to be 71% (95% confidence interval: 56-81%). This result
      remained practically the same after changing the definition used for tuberculosis
      cases (VE = 75% for a threshold with a score of 15 instead of 6, VE = 74% when
      only confirmed cases were considered). There was no difference between the two
      groups in the variables measuring intensity of contact with the source of
      contamination, but there was a difference in age distribution. Vaccine efficacy
      adjusted for this factor was the same as the crude VE. CONCLUSION: This study,
      based on a methodology that controls for most of the risks of bias inherent to
      field efficacy measurement, confirms the protective capacity of neonatal BCG
      against childhood tuberculosis. Therefore BCG vaccination at birth must remain a
      public health priority especially in countries with high incidence of the
      disease.

PMID- 8557439
TI  - Assessment of the direct effectiveness of BC meningococcal vaccine in Rio de
      Janeiro, Brazil: a case-control study.
AB  - BACKGROUND: Meningococcal disease is still a serious public health problem in
      many countries. A vaccine produced by Cuba was the first product against B
      meningococcus available on a large scale. In an attempt to control the increasing
      incidence of this serogroup in greater Rio de Janeiro, Brazil, the vaccine was
      used in 1990 in children aged 6 months-9 years. About 1.6 million children were
      vaccinated. METHODS: In order to assess the direct effectiveness of the vaccine
      in preventing disease, we conducted a case-control study during the first year
      after vaccination. Using a hospital-based census, we selected all children
      hospitalized with meningococcal disease and sampled the control group among
      children hospitalized with other types of meningitis. Vaccine effectiveness was
      estimated from the relationship, 1-OR, where OR (odds ratio) was the exponential
      of the logistic regression coefficient for the association between meningococcal
      disease and previous vaccination. RESULTS: A total of 275 cases and 279 controls
      were selected between September 1990 and October 1991. The summary adjusted
      measure of protection against serogroup B was 54% (95% confidence interval [CI]:
      20-74%). Estimated protection varied among different age strata and place of
      residence, being high among children aged > or = 4 years, 71% (95% CI: 34-87%),
      and among those who lived in the City of Rio de Janeiro, 74% (95% CI: 42-89%).
      CONCLUSIONS: The results suggest that the vaccine produced by Cuba may offer
      protection against serogroup B meningococcal disease, but its effects may not be
      homogeneous.

PMID- 8557441
TI  - Estimation of prevalence rate ratios from cross-sectional data.

PMID- 8557440
TI  - Maternal reporting of acute respiratory infection in Egypt.
AB  - BACKGROUND: Acute respiratory infection (ARI) is a major cause of childhood
      morbidity and mortality in developing countries. Community surveys are used to
      determine the proportion of children with ARI for whom care is sought by
      questioning mothers about the signs and symptoms of illness episodes. The
      validity of this approach has been studied infrequently. METHODS: We evaluated
      maternal reporting of signs and symptoms 2 and 4 weeks after diagnosis among 271
      Egyptian children < 5 years old. Children with ARI were evaluated by physical
      examination, chest radiography, and pulse oximetry, and were alternately assigned
      for a maternal interview about the episode 14 or 28 days later. RESULTS: For
      radiographically-defined acute lower respiratory infection (ALRI), the
      sensitivity of several symptoms for combined open- and close-ended questions was
      relatively high: nahagan (deep or rapid breathing) (80%), nafas sarie (fast
      breathing) (66%), and kharfasha (coarse breath sounds) (63%). The specificity of
      these terms was 50-68%. The specificity was inversely related to the follow-up
      time. No term provided both a sensitivity and specificity of > 50% at day 28
      across the radiographically, clinically- and pulse oximetry-based definitions of
      ALRI. Spontaneously mentioned karshet nafas (difficult or rapid breathing) at 14
      days had a specificity and sensitivity for radiographic ALRI of 87% and 41%,
      respectively, suggesting that this term is a good choice for community surveys.
      CONCLUSIONS: Maternal reporting of ARI symptoms is non-specific 2 and 4 weeks
      after diagnosis but may be useful for monitoring trends in the proportion of
      children with pneumonia who receive medical care. To maximize specificity, ARI
      programmes should generally use a recall period of 2 weeks.

PMID- 8557442
TI  - The poverty of Popperian epidemiology.

PMID- 8557443
TI  - The transmission of Helicobacter pylori. A critical review of the evidence.
AB  - This paper critically reviews the reported data regarding the transmission of
      Helicobacter pylori. The mode of transmission remains poorly understood; no
      single transmission pathway has been clearly identified. Laboratory studies have
      experienced difficulty in isolating this organism from material other than
      gastric tissue. The problematic detection of this bacterium has presented
      obstacles to pinpointing portals of entry and exit and to implicating or ruling
      out environmental reservoirs. It is shown additionally that knowledge of H.
      pylori transmission is limited due to lack of solid epidemiological evidence from
      population-based analyses that adequately consider confounding. Reported
      observations in general support a person-to-person mode of transmission that
      occurs most frequently early in life; H. pylori is consistently linked to
      conditions associated with residential crowding in childhood. Laboratory studies
      have yielded evidence in favour of both faecal-oral and oral-oral pathways.
      However, a role for either waterborne or zoonotic transmission has not been ruled
      out. The failure of investigations to single out a mode of transmission for H.
      pylori signals the possibility of multiple transmission pathways.

PMID- 8557444
TI  - The impact of family history of colon cancer on survival after diagnosis with
      colon cancer.
AB  - BACKGROUND: The impact of family history of colon cancer on survival after
      diagnosis with colon cancer is generally unknown. It is possible that family
      history is indicative of a genetically inherited form of disease which may alter
      survival. METHODS: The Utah Population Database was used to evaluate survival
      after diagnosis with colon cancer among 2236 first primary colon cancer cases.
      This database includes detailed information about family history and is linked to
      the Utah Cancer Registry to obtain tumour information. RESULTS: Stage at
      diagnosis was the primary factor associated with death from all causes and from
      colon cancer. An older age at diagnosis, being female, and having a tumour in the
      ascending segment of the colon also were associated with poorer survival,
      although after adjusting for stage at diagnosis these associations disappeared.
      Having a family history of colon cancer had little impact on survival patterns
      although there were suggestions that men who were diagnosed at age < or = 55 were
      more likely to die from all causes as well as colon cancer if they had a sibling
      with colon cancer (hazard rate ratio [HRR] 2.50, 95% confidence interval [CI]:
      1.03-6.10) relative to men > 55 without a sibling with colon cancer. CONCLUSIONS:
      From these data it appears that the major factor which increases survival is
      being diagnosed at an early stage of disease. These data also suggest that
      younger men who have a sibling with colon cancer may have a different form of
      colon cancer which increases their risk of dying.

PMID- 8557445
TI  - Changing trends in the epidemiology of malignant melanoma: gender differences and
      their implications for public health.
AB  - BACKGROUND: Skin cancer has been identified as a key area in the English health
      strategy. Review of trends in the epidemiology of melanoma by age, sex and social
      class can contribute to ensuring that preventive efforts are targeted
      appropriately and subsequently to monitoring the effects of campaigns. METHODS:
      Descriptive epidemiological study using data for both sexes from cancer
      registrations by age (England & Wales 1971-1989), and from mortality statistics
      by age (England & Wales 1951-1970, England 1969-1992) and by social class
      (England & Wales 1970-1972 for men and women, England & Wales 1979-1980, 1982
      1983 for men and Great Britain 1979-1980, 1982-1983 for women). Analysis used age
      standardized and age-specific registration rates by sex, age-standardized and age
      specific mortality rates by sex and standardized mortality ratios by sex and by
      social class. Cohort effects are presented based on model fitting of age- and
      cohort-specific mortality rates for the period 1950-1989. RESULTS: Registration
      rates of new cases of malignant melanoma increased sharply in both sexes between
      1971 and 1989 by 190% in men and 137% in women. Between 1970/1972 and 1990/1992
      age-standardized mortality rates increased by 92% in men and 43% in women. In the
      15-34 age group mortality rates have declined in women since the late 1970s
      whilst remaining level in men. The pattern of significantly higher mortality for
      both men and women in non-manual occupational groups had by the early 1980s
      diminished in women although it remained in men. In non-manual groups the
      mortality rate was higher in men than in women whilst for manual groups the
      opposite was true. CONCLUSION: A difference in trends in mortality from malignant
      melanoma between the sexes was demonstrated. Men are an important target group
      for preventive efforts despite their lower incidence of melanoma. They have a
      higher mortality rate which is increasing, less knowledge about appropriate
      primary and secondary preventive measures, present later with disease and respond
      less to traditional health education approaches. The findings have implications
      for the planning of primary and secondary prevention programmes.

PMID- 8557446
TI  - Do cardiovascular disease risk factors predict all-cause mortality?
AB  - BACKGROUND: The purpose of this study is to describe associations between a
      number of standard cardiovascular risk factors and all-cause mortality. METHOD:
      Mortality data were collected for a randomly selected cohort of 1029 New Zealand
      men aged 35-64 years, followed up over a 9-year period. A proportional hazards
      regression model was used to estimate the relative risks (RR) for all-cause
      mortality associated with a number of cardiovascular risk factors. RESULTS: In
      all, 96 deaths occurred over the 9-year period, of which 50% were due to
      cardiovascular causes. All-cause mortality was positively associated with
      cigarette smoking (age-adjusted RR = 2.01, 95% CI:1.15-3.53, current versus
      never), systolic blood pressure (age-adjusted RR = 2.18, 95% CI:1.23-4.44, upper
      versus lower tertile), and body mass index (age-adjusted RR = 1.59, 95% CI:0.94
      2.66, upper versus lower tertile) and inversely associated with high density
      lipoprotein (HDL)-cholesterol (age-adjusted RR = 0.45, 95% CI:0.25-0.80, upper
      versus lower tertile). All-cause mortality was only weakly associated with serum
      total cholesterol (age-adjusted RR = 1.19, 95% CI:0.70-1.99, upper versus lower
      tertile), and there was no evidence of a U-shaped relationship for this risk
      factor. There was an inverse association between all-cause mortality and
      socioeconomic status (age-adjusted RR = 1.70, 95% CI:1.03-2.80, lower versus
      upper). Light alcohol consumption was associated with reduced all-cause mortality
      (age-adjusted RR = 0.63, 95% CI:0.37-1.05, light versus teetotal), but this
      benefit did not persist for alcohol consumption above about three standard drinks
      per day. CONCLUSIONS: The findings of this study indicate that the standard
      cardiovascular risk factors are likely to have a beneficial impact on all-cause
      mortality as well as cardiovascular disease in middle-aged and older men.

PMID- 8557447
TI  - Relation of fibrinogen to lifestyles and to cardiovascular risk factors in a
      working population.
AB  - BACKGROUND: The association between fibrinogen and smoking behaviour, age, body
      mass index, blood pressure, heart rate and plasma lipid profile, was assessed in
      a cohort of middle-aged working men. METHODS: Seven hundred and forty five
      subjects were examined as part of a health intervention programme at the work
      site. Nine subjects were excluded from the study because of prevalent diabetes.
      Correlates of plasma fibrinogen concentrations were evaluated through univariate
      and multivariate methods. RESULTS: In multiple regression analysis fibrinogen
      correlated with age, smoking behaviour, apolipoprotein B (apo B) apolipoprotein A
      I (apo A-I) and lipoprotein (a) (Lp(a)) levels, which together explained 11% of
      the variation in fibrinogen concentration. From this model, fibrinogen
      concentration was associated with an increase of 13.6 mg/dl for every 10 years'
      increase in age, 28.2 mg/dl if a person smoked, and 4.6 mg/dl and 3.8 mg/dl with
      a 20 mg/dl rise in respectively apo B and Lp(a). A 20 mg/dl increase in apo A-I
      concentrations was estimated to be associated with a 6.0 mg/dl lower fibrinogen
      level. CONCLUSION: The data indicate that both biochemical and lifestyle factors
      are related to the plasma fibrinogen concentration; these interactions may
      explain partly the relationship between fibrinogen and cardiovascular disease.

PMID- 8557448
TI  - Crohn's disease and ulcerative colitis in England and the Oxford record linkage
      study area: a profile of hospitalized morbidity.
AB  - BACKGROUND: Crohn's disease and ulcerative colitis are chronic relapsing
      conditions. National hospital statistics in England only provide episode-based
      admission rates and cannot be used to identify multiple admissions per person. We
      used record linkage to provide a person-based profile of admission rates.
      METHODS: Age-standardized admission rates were calculated from the computer tapes
      of the Hospital In-patient Enquiry (HIPE) for 1970-1985 and the Oxford Record
      Linkage Study (ORLS) for the period 1970-1986. In addition, annual hospitalized
      prevalence, first hospital admission rates (as a proxy for incidence) and
      readmission rates were calculated for the Oxford population. Predictors of
      relapses were assessed by logistic regression models. RESULTS: Episode-based
      admission rates for Crohn's disease increased over time, both nationally and in
      Oxford. In Oxford, hospitalized incidence rates showed no increase for Crohn's
      disease. Neither episode-based nor person-based rates increased for ulcerative
      colitis. Relapses resulting in hospital admission were more common for Crohn's
      disease than for ulcerative colitis. They increased over time. We showed the
      influence of some sociodemographic characteristics (age, social class, district
      of residence, operations) on relapses. CONCLUSIONS: Data on episodes of hospital
      care for Crohn's disease showed an increase over time while data related to
      individuals in receipt of care showed no increase over time. Unlinked episodes of
      hospital care are of limited value when studying temporal trends for chronic
      conditions with multiple admissions.

PMID- 8557449
TI  - A comparative study of two methods for the measurement of alcohol consumption in
      the general population.
AB  - BACKGROUND: One of the major methodological problems in measuring alcohol
      consumption in a general population and in selected groups is underreporting.
      METHODS: The present study is based on a general health questionnaire survey of a
      random sample of about 4000 adults aged 20-74 years in an inner-city area in each
      of two major Swedish cities in 1991. The questionnaire included items both about
      alcohol consumption frequency and the usual amount of intake--the commonly used
      quantity-frequency (QF) method--and other questions about the consumption during
      work-days and weekends during a 'normal week'--the period-specific normal week
      (PSNW) method. RESULTS: With a few exceptions, the reported mean consumption and
      the proportion of high consumers was higher with the latter approach,
      irrespective of sex, age, socio-demographic factors, smoking and health status,
      i.e. for variables which are commonly used as confounders or effect modifiers.
      The differences between the methods was greater among women. The internal non
      response rate was higher with the PSNW method but the non-responders had a
      comparatively low consumption, when measured with the QF method. CONCLUSION: The
      PSNW method has higher validity and greater precision for the measurement of
      alcohol consumption and, thus, is superior to the QF method. The sex differences
      are notable and warrant further studies focusing on sex-related modes of
      answering.

PMID- 8557450
TI  - A comparison of sisterhood information on causes of maternal death with the
      registration causes of maternal death in Matlab, Bangladesh.
AB  - BACKGROUND: To explore whether causes of maternal death can be investigated using
      the sisterhood method, an indirect method for providing a community-based
      estimate of the level of maternal mortality, this study compares the sisterhood
      causes of maternal death with the Matlab Demographic Surveillance System's (DSS)
      causes of maternal death. METHODS: Data for this study came from the Matlab DSS,
      which has been in operation since 1966 as a field site of the International
      Centre for Diarrhoeal Disease Research, Bangladesh. The maternal deaths that
      occurred during the 15-year period from 1976 to 1990 in the Matlab DSS area are
      the basis of this study. A sisterhood survey was conducted in Matlab in November
      and December 1991 to collect information on conditions, events and symptoms that
      preceded death. The collected information was evaluated to assign a most likely
      cause of maternal death. The sisterhood survey cause of maternal death was then
      compared with the DSS cause of maternal death. RESULTS: Cause of death could not
      be assigned with reasonable confidence for 34 (11%) of the 305 maternal deaths
      for which information was collected. For the remaining deaths, the agreement
      between the two classification systems was generally high for most cause-of-death
      categories considered. CONCLUSIONS: Though cause-of-death information obtained by
      the sisterhood method will always be subject to some error, it can provide an
      indication of an overall distribution of causes of maternal deaths. This data can
      be used for the planning of programmes aimed at reducing maternal mortality and
      for the evaluation of such programmes over time.

PMID- 8557451
TI  - Prevalence of cerebral palsy in twins, triplets and quadruplets.
AB  - BACKGROUND: Twins and triplets are at higher risk of cerebral palsy than
      singletons. This study investigated the degree of risk for cerebral palsy in
      twins, triplets and quadruplets, and identified factors associated with the
      increased risk. METHODS: The subjects were recruited from the Kinki University
      Twin and Higher Order Multiple Births Registry. RESULTS: The subjects were 705
      twins pairs (1410 twins), 96 sets of triplets (287 triplets excluding one infant
      death), and 7 sets of quadruplets (27 quadruplets excluding one infant death),
      who were born after 1977. The prevalence of cerebral palsy was 0.9% among 1410
      twins, 3.1% among 287 triplets, and 11.1% among 27 quadruplets. Furthermore, the
      risks of producing at least one child with cerebral palsy were 1.5%, 8.0%, 42.9%
      in twin, triplet, quadruplet pregnancies, respectively. After adjusting for each
      associated factor using logistic regression, the risk of cerebral palsy was
      significantly associated with decrease in gestational age and asphyxia. The odds
      ratio indicated that infants whose gestational age was < 32 weeks were 20 times
      more likely to develop cerebral palsy than infants whose gestational age was > or
      = 36 weeks. CONCLUSIONS: The prevalence of cerebral palsy in triplets and
      quadruplets was higher than that in twins. Lower gestational age was associated
      with a greater risk of cerebral palsy.

PMID- 8557452
TI  - Dietary determinants of a non-progressive spastic paraparesis (Konzo): a case
      referent study in a high incidence area of Zaire.
AB  - BACKGROUND: Konzo is an upper motor neuron disease in Africa, characterized by an
      abrupt onset of a permanent but non-progressive spastic paraparesis. It is named
      after the local designation in the first report from Zaire. Konzo has been
      attributed to a metabolic insult from the combined effect of high cyanide and low
      sulphur intake from several weeks of exclusive consumption of insufficiently
      processed bitter cassava roots. METHODS: The association between insufficient
      soaking of cassava roots and konzo is assessed in a matched case-referent study
      with multivariate conditional logistic regression including 57 case-referent
      pairs from a rural high incidence community of Zaire. RESULTS: In the
      multivariate analysis short processing of cassava in the form of only 2 nights
      soaking yielded an odds ratio of 11.0 (95% confidence interval 1.7-73) when
      controlling for poverty-related factors and diet. We also show a dose-response
      relationship for insufficient cassava soaking, both unadjusted and adjusted for
      potential confounders. CONCLUSIONS: This study supports a causal relationship
      between insufficient processing of bitter cassava and konzo.

PMID- 8557453
TI  - A case-control study of traffic risk factors and child pedestrian injury.
AB  - BACKGROUND: Pedestrian injuries in children constitute an important cause of
      mortality and morbidity. Specific hazards which contribute to these injuries need
      to be identified to enable the development of preventive strategies. METHODS: A
      population-based case-control study was conducted in which 40 aspects of traffic
      and road environment that contribute to the likelihood of childhood pedestrian
      injury were examined. The factors of interest were measured at 100 places of
      injury and 200 control sites between December 1991 and December 1993. RESULTS:
      The volume of traffic (odds ratio [OR] = 2.16 for an increase of 100 vehicles per
      hour) in combination with the proportion of vehicles exceeding the speed limit
      (OR = 1.04) for each 1% increase in average speed, and the presence of footpaths
      (OR = 11.0) were associated with significant increase in the risk of injury. A
      graded inverse relationship was present between socioeconomic status and the odds
      of pedestrian injury. CONCLUSIONS: These findings have obvious implications for
      public health as features of the physical environment are potentially modifiable.

PMID- 8557454
TI  - Discontinuity indices: a tool for epidemiological studies on breastfeeding.
AB  - BACKGROUND: The Discontinuity Index (DI), which measures the percentage of
      infants who were exclusively breastfed (EBF) at the beginning of a given age
      interval and had abandoned this mode of feeding at its end, and the relative
      weight of this discontinuation, was introduced and employed in the National
      Survey on Breast Feeding and Infant Feeding Practices carried out in Cuba in
      1990. The aim of this article is to illustrate, through a specific example, the
      quality of DI as a simple procedure for assessing breastfeeding trends. METHODS:
      The prevalence of EBF in the 14 provinces of Cuba at discharge from the maternity
      services and at 30, 60, 120, and 180 days of age, was obtained using data from a
      national sample of 6661 infants (4820 urban and 1791 rural) which were processed
      by means of a logistic regression model. Cumulative DI were calculated for the
      intervals 0-30, 0-60, 0-120 and 0-180 days, and partial DI for the terms 30-60,
      60-120 and 120-180 days, for each province and for the whole country. RESULTS:
      Cumulative DI show the progress of cessation of breastfeeding and are strongly
      influenced by previous intervals. The Eastern provinces showed the lowest figures
      at most of the terms. Discontinuation during the first month of life was
      particularly high in two Western provinces. Partial DI are more specific and
      allow discrimination of the intervals at which EBF discontinuation is more
      frequent. The highest values were observed between 4 and 6 months. CONCLUSIONS:
      Discontinuity indices are useful complements to prevalence rates in
      epidemiological studies of breastfeeding. The separate analysis of
      discontinuation in different periods can be highly useful when comparing trends
      and in the study of the impact of breastfeeding promotion programmes focused on
      different age intervals.

PMID- 8557455
TI  - Weight-for-height indices of adiposity: relationships with height in childhood
      and early adult life.
AB  - BACKGROUND: The expense and inconvenience of accurate assessment of fat/lean body
      mass have engendered a reliance on weight-for-height indices in epidemiological
      investigations; indices which are independent of height have been considered
      desirable. METHODS: The relationship between weight-for-height and height was
      examined using the 1958 birth cohort, National Child Development Study, at ages
      7, 11, 16, 23 and 33 years. For each age the sample was divided into a number of
      height groups; underweight, overweight and obesity were defined by relative
      weight (RW) and body mass index (BMI) in childhood and adulthood respectively.
      RESULTS: In childhood the variance of RW showed substantial and systematic
      associations with height. Both underweight and overweight/obesity were related to
      height: patterns differed by age and sex, being most evident at age 7 in both
      sexes, continuing at age 11 (but more so in boys), and disappearing by age 16. At
      age 23, underweight was more prevalent and overweight and obesity less prevalent
      in the taller groups due to a linear correlation between BMI and height. At age
      33 obesity was less prevalent in taller groups, particularly in women.
      CONCLUSIONS: These findings have implications for studies of obesity comparing
      groups which differ in height, for example, different cohorts or social classes.
      In the short term, interpretation of such results should take account of the
      phenomenon described. In the longer term, information is needed on the
      relationship between height and more precise assessment of adiposity to confirm
      the findings of the current analysis.

PMID- 8557456
TI  - Physical activity, illness and nutritional status among adults in a rural
      Ethiopian community.
AB  - BACKGROUND: From Africa, our knowledge on how malnutrition and diseases influence
      the ability to work is limited. In a one-year population-based study, we
      investigated the effects of nutritional status, illness and socioeconomic factors
      on the activity pattern in a rural population in southern Ethiopia. METHODS: From
      July 1991 to June 1992, 226 people (109 men and 117 women) from the Elka na
      Mataramofa village in the Rift Valley were examined every 3 months. Information
      on the occurrence of illness and measurement of nutritional status were collected
      every 3 months. At the same time we interviewed each person for seven consecutive
      days to assess the pattern of activities. RESULTS: Men and women had a mean
      estimated energy expenditure (SD) of 2937 kcal (951) and 1977 (513) kcal,
      respectively. The mean body mass index (BMI) (SD) was 19.7 (2.3) for men and 20.0
      (2.6) for women. Men showed a significant seasonal variation in estimated energy
      expenditure that was highest during the pre-harvest time. Women did not show such
      a seasonal variation. In a multivariate analysis, sex, age, state of nutrition,
      period prevalence and severity of diseases and seasonality influenced estimated
      energy expenditures. CONCLUSIONS: Both low BMI and illness are significantly
      associated with low estimated energy expenditure. Most likely, this represents an
      example of the vicious circle of malnutrition, disease and activity that affects
      subsistence farming communities. Development work that improves the state of
      nutrition and health of the adult population may therefore enhance the work
      performance of rural populations.

PMID- 8557457
TI  - Increase in incidence of insulin-dependent diabetes mellitus among children in
      Finland.
AB  - BACKGROUND: In Finland, the incidence of insulin-dependent diabetes mellitus
      (IDDM) in children aged < 15 years is the highest in the world. The aim of this
      study was to determine the temporal variation in incidence and the age
      distribution at diagnosis of IDDM. SUBJECTS AND METHODS: Data on incidence of
      IDDM in Finland nationwide were obtained from two sources: the Central Drug
      Registry for the years 1965-1986 (6195 IDDM cases) and the prospective IDDM
      registry for the years 1987-1992 (2062 IDDM cases). The annual incidence rates
      were calculated per 100,000 population. The increase in incidence from 1965 to
      1992 was estimated by fitting the linear regression with the annual incidence
      data. RESULTS: The overall incidence of IDDM between 1987 and 1992 was 36 per
      100,000/year. During 1965-1992 the increase was almost linear. The regression
      based change in incidence was 2.8% per year. In the 1970s the increase in
      incidence was steepest in 5-9 year olds and since the mid-1980s in those < 5
      years old at diagnosis. CONCLUSIONS: The incidence of IDDM in Finnish children
      seems to increase further. During the last decades the increase in incidence has
      been almost linear with occasional peaks. The age-at-diagnosis of IDDM has been
      moving towards the younger ages, and differences in incidence between age groups
      have now almost disappeared among Finnish children aged 1-14 years.

PMID- 8557458
TI  - A case-control study of aplastic anaemia: occupational exposures. The French
      Cooperative Group for Epidemiological Study of Aplastic Anaemia.
AB  - BACKGROUND: Based on the national register of new cases of aplastic anaemia (AA)
      begun in France in 1984, a case-control study was conducted to explore the
      aetiology of the disease. METHODS: Cases were all included in the French national
      register of AA. Two different groups of controls were derived with individual
      matching; one group from hospitalized patients in the same hospital; the other
      group from neighbours named by the case. A 15-year occupational history was
      collected through interview and then grouped into exposure categories by jobs
      done for one year or more. The study included 98 cases, 181 hospitalized
      controls, and 72 neighbours aged 18-70 years. RESULTS: No differences appeared
      between the cases and both groups of controls relative to any group of occupation
      investigated. However, a borderline non-significant small excess for exposure to
      pesticides was observed among the cases when compared to hospitalized controls.
      Whatever the control group, no association was found between AA and exposure to
      solvents, ionizing radiation, fuel, oils and grease. A positive relationship
      between exposure to glues and AA was observed, as well as a trend towards an
      increased risk after exposure to paints. CONCLUSIONS: This large-scale case
      control study confirmed the vanishing role of previously known toxic substances
      in the aetiology of AA. However, a higher proportion of AA patients reported
      exposure to paints and to glues, a relationship which needs further investigation
      because of the diversity of compounds included in these products.

PMID- 8557459
TI  - Gwendolen Rees F.R.S. 1906-1994.

PMID- 8557460
TI  - Biochemical analyses on single amphidial glands, excretory-secretory gland cells,
      pharyngeal glands and their secretions from the avian nematode Syngamus trachea.
AB  - The gape nematode, Syngamus trachea, has been used as a model to study nematode
      secretions. Individual and intact pairs of amphidial glands, pharyngeal glands
      and pairs of excretory-secretory gland cells have been dissected and their
      secretory products analysed. The protein profiles of each gland and the total
      nematode secretions were analysed on 12.5% homogeneous SDS-PAGE minigels. The
      protein analyses revealed that the structural protein profile of each gland is
      different. The amphidial gland secretes two major proteins of 36.0 and 41.5 kDa,
      the excretory-secretory gland cell secretes a protein of 28.2 kDa and a protein
      of 14.3 kDa, and the pharyngeal gland secretes proteins of 41.5 and 14.6 kDa.
      Analysis of the total nematode secretions revealed all of the above major
      secretory proteins and an additional protein of 49.3 kDa. Syngamus trachea
      secretes acetylcholinesterases and its secretions contain multiple proteases.

PMID- 8557461
TI  - Coomera: a new genus of Fellodistomidae (Digenea) from Monodactylus argenteus
      (Monodactylidae) of southern Queensland, Australia.
AB  - A new genus, Coomera, is erected to accommodate C. brayi new species, here
      described from the intestine and rectum of Monodactylus argenteus from southern
      Queensland, Australia. The species is characterised by a single gut caecum,
      conical pharynx, oblique testes, pars prostatica lined with anucleate vesicles, a
      large genital atrium, and a large muscular cirrus. Despite the single caecum, C.
      brayi is not assigned to the Monascinae for the following reasons: the sub
      terminal oral sucker opens in a round aperture rather than a medial slit, the
      ventral sucker is larger than the oral sucker, a pre-pharynx is present, the
      pharynx is conical rather than elongate and the testes are symmetrical rather
      than tandem. These character states are shared with the Fellodistominae to which
      we assign this genus, suggesting that possession of a single caecum is
      homoplasious within the Fellodistomidae.

PMID- 8557462
TI  - Micro-evolutionary implications of allozymic and morphometric variations in
      sealworms Pseudoterranova sp. (Ascaridoidea: Anisakidae) among sympatric hosts
      from the southeastern Pacific Ocean.
AB  - We found significant morphometric and electrophoretic differences between
      sealworm larvae collected from four sympatric fish host species off the central
      coast of Chile. The South American sea lion, Otaria byronia, is a suitable host
      and most likely the only definitive host species in the study area. Morphological
      patterns of caudal papillae in adult males collected from sea lions and
      electrophoretic evidence from larvae and adults substantiate our conclusion that
      they belong to just one, new species yet to be described. The genetic and
      morphometric differences found between sealworm larvae from sympatric fish hosts
      may be due to selective pressures arising from the internal environment of the
      intermediate hosts, although they may serve only for passing sequential filters
      along the life cycle. The discussion deals with the roles that definitive and
      intermediate hosts may play in the micro-evolutionary processes of sealworms.

PMID- 8557463
TI  - Morphological polymorphism in the nematode Teladorsagia circumcincta in relation
      to age of larvae, infection mode and lamb characteristics in experimental
      conditions.
AB  - Variations in the proportion of the less-frequent morph of Teladorsagia
      circumcincta, T. c. trifurcata, were studied under experimental conditions.
      Infections with older larvae (over 7 months of age at 4 degrees C) yield a lower
      proportion of T. c. trifurcata compared with those obtained from fresh larvae (15
      days). This phenomenon could account for the reduction in the proportion of the
      morph trifurcata in two isolates that were acclimated to laboratory rearing for
      several generations. The infection mode (single or trickle infections did not
      significantly modify the proportions of both morphs. The morph trifurcata was
      found in higher proportions (> 5.5%) in more susceptible male and/or Romanov
      lambs, and in lower proportions (< 2.5%) in less susceptible female and/or
      Merinos d'Arles lambs.

PMID- 8557464
TI  - Increased coprophagic activity of the beetle, Tenebrio molitor, on feces
      containing eggs of the tapeworm, Hymenolepis diminuta.
AB  - When provided with fecal pellets from uninfected (control) rats and rats infected
      with the tapeworm Hymenolepis diminuta, more fed and starved (72 h) female and
      starved male Tenebrio molitor fed on fecal pellets from infected- than from
      control rats; compared to fecal pellets from controls rats, fed males avoided the
      infective fecal pellets. Uninfective and infective fecal pellets had similar
      moisture contents, so increased coprophagic activity was not due to differences
      in moisture content. Fed and starved males and females were fed on fecal pellets
      containing tapeworm eggs and examined for cysticercoids. Significantly greater
      numbers of starved beetles than fed beetles were infected with cysticercoids, but
      the numbers of infected males and females within each treatment were not
      significantly different. On the other hand, males contained significantly greater
      numbers of cysticercoids than did females, and there was no significant
      difference between the numbers of cysticercoids recovered from fed and starved
      beetles. The data support the hypothesis that the feeding behavior of T. molitor
      on rat feces is altered by the presence of tapeworm eggs. The data demonstrated
      further that transmission dynamics are affected by a complex interaction of the
      beetle's sex and nutritional status.

PMID- 8557465
TI  - In vitro studies on the relative sensitivity to ivermectin of Necator americanus
      and Ancylostoma ceylanicum.
AB  - Experiments were carried out to compare the sensitivity of Ancylostoma ceylanicum
      and Necator americanus to ivermectin (IVM) and pyrantel in vitro. Loss of
      motility and inhibition of ingestion by IVM were compared and A. ceylanicum was
      found to be approximately 40-50 times more sensitive to IVM than N. americanus.
      Both species showed a similar sensitivity to pyrantel. Uptake of [3H]IVM across
      the cuticle was compared and shown to be unlikely to account for the differences
      in sensitivity to IVM between the two species.

PMID- 8557466
TI  - Comparison of hepatic and extrahepatic drug-metabolizing enzyme activities in
      rats given single or multiple challenge infections with Fasciola hepatica.
AB  - The activity of drug-metabolizing enzymes was compared in liver, kidneys and
      lungs of rats given single or repetitive fluke infections. Fascioliasis was
      induced by oral administration of 20 metacercariae of F. hepatica to rats, either
      6, or 12 and 6, or 12, 9 and 6 weeks before sacrifice. In the liver of mono
      infected rats, significant reductions (24-67%) were observed in microsomal
      content of cytochrome P450 and all P450-dependent monooxygenases investigated.
      Conjugations to glutathione or acetate were lowered by 34-50% in these animals.
      In multiply infected animals, a majority of specific enzymatic activities were
      unchanged, while some monooxygenase activities such as aminopyrine demethylation
      or benzo(a)pyrene hydroxylation were increased by 26-76% in the liver of tri
      infected rats. A renal compensatory process occurred in all infected groups,
      since cytochrome P450, benzphetamine demethylation and glutathione conjugation
      were significantly increased. By contrast, dealkylation of benzphetamine and
      pentoxyresorufin were decreased in the lungs of monoinfected rats. The
      development of parasite resistance would account for the recovery of liver drug
      metabolizing capabilities in multi-infected animals.

PMID- 8557467
TI  - Influence of diet type on the kinetic disposition of fenbendazole in cattle and
      buffalo.
AB  - The plasma concentration profiles of fenbendazole (FBZ), FBZ-sulphoxide and FBZ
      sulphone were measured following intraruminal administration of FBZ at 7.5 mg kg
      1 body weight in cattle and buffalo offered 3 different diets: 100% dry mature
      sorghum hay, 100% green Pennisetum spp. and a 50:50 mix of these 2 diets.
      Changing the diet from dry to green fodder resulted in significantly lower
      systemic availability of FBZ and its metabolites in both species. Buffalo had a
      lower systemic availability of the drug than cattle on the dry diet and the
      difference between species increased when the diet included green fodder. It is
      suggested that decreased transit time of digesta on the green fodder reduced
      systemic concentrations by reducing the time available for gastrointestinal
      absorption of the drug.

PMID- 8557468
TI  - The pharmacokinetics of albendazole metabolites following administration of
      albendazole, albendazole sulfoxide and netobimin to one-month- and eight-month
      old sheep.
AB  - The principal metabolites detected in plasma of sheep following oral
      administration of albendazole (ABZ), albendazole sulfoxide (ABSO) and netobimin
      (NTB) each at 5.0 mg kg-1 body weight were ABSO and albendazole sulfone (ABSO2).
      The areas under the plasma concentration-time curve (AUC) for ABSO and ABSO2 were
      significantly (P < 0.05) larger following administration for ABSO than NTB in 1
      month- and 8-month-old sheep. The AUC for the ABSO and ABSO2 metabolites were
      larger following administration of ABZ than NTB in 1-month- but not 8-month-old
      sheep and the AUC of the ABSO and ABSO2 metabolites were greater following ABSO
      than ABZ as parent compound in 8-month-old sheep only. The larger AUC values for
      metabolites following administration of ABSO as the parent compound were
      generally coincident with significantly higher maximum (Cmax) concentrations and
      not with persistence in the body, since mean residence times (MRT) of the
      metabolites were not significantly different from those determined following ABZ
      and NTB as parent compounds. The lower metabolite concentration following
      administration of NTB may have been a feature of its requirement for metabolic
      conversion and its larger molecular weight. Correction of AUC values for
      molecular weight removed any significant differences between AUC values for
      either metabolite in 8-month-old lambs. The corrected metabolite AUCs following
      NTB were, however, significantly lower than those following ABSO administration
      in 1-month-old lambs, suggesting that immature metabolic processes in these
      animals contributed to the lower relative bioavailability of NTB in this age
      group. Age did not affect the disposition of metabolites following ABZ or ABSO
      but the AUC of the ABSO metabolite following NTB was significantly (P = 0.014)
      lower in 1-month- than in 8-month-old sheep.

PMID- 8557469
TI  - A protein secreted by Trypanosoma cruzi capable of inducing the entry of inert
      particles into HeLa cells.
AB  - Trypanosoma cruzi requires an intracellular environment to multiply within its
      mammalian host. We describe the purification and some properties of a protein
      secreted exclusively by the metacyclic (infective) forms of the parasite. This
      permeabilizing protein (relative molecular mass 64,000) was secreted under our
      experimental conditions only when the parasites interacted with HeLa cells, HeLa
      membranes, or wheat-germ lectin. The protein is thermostable, and its biological
      activity is inhibited by formaldehyde but not by ethanol or acetone. At low
      concentrations and over short treatment times, this protein acts as a
      permeabilizer and induces endocytosis. No significant protease or neuraminidase
      activity was found. When adsorbed onto bentonite particles and incubated in the
      presence of non-phagocytic cells the protein facilitated the penetration of the
      particles into the cells. Immune serum directed against the protein neutralized
      its cytotoxic action and reduced the rate of penetration of metacyclic forms into
      both macrophages and non-phagocytic cells. Our results suggest that the protein
      secreted by the parasite plays a key role in the penetration of its infective
      form into the host cell.

PMID- 8557470
TI  - Humoral and cellular immune responses to Fasciola hepatica experimental primary
      and secondary infection in sheep.
AB  - Blood leukocyte changes, serum hepatic enzyme levels, lymphocyte proliferation in
      response to Concanavalin A (ConA) and to parasitic excretory-secretory products
      (FhESP), and antibody (IgG and IgM) responses (ELISA and Western blot) were
      studied in sheep, the natural susceptible host of F. hepatica, during the first 3
      months of an experimental primary or secondary infection. The proportion of
      flukes established was similar in once- and twice-infected groups, but the flukes
      originating from the secondary infection migrated more rapidly to the bile ducts.
      Primary infection induced a marked peripheral eosinophilia from 3 to 13 weeks
      post-primary infection (PPIW). FhESP-specific IgM were produced from PPIW 2 with
      peaks in PPIW 3 and 9-10; FhESP-specific IgG increased from PPIW 2 to 6 and
      became stable afterwards. Western blotting revealed 12 major antigenic fractions
      in FhESP from 12, 15, 20, 24, 27, 28.5, 30, 41, 51, 56, 69 and 156 kDa; some non
      specific ones have been characterized. A sequential recognition of higher then
      lower molecular weight antigens was observed. FhESP-specific lymphocyte
      proliferation was marked from PPIW 2 to 5. In contrast, ConA stimulation of
      lymphocytes was decreased. After secondary infection in PPIW 6, immune responses
      were modified. The ConA-induced lymphocyte proliferation was transitorily
      increased. In contrast, the humoral response, in particular against the early
      recognized antigens, and the level and the duration of the FhESP-specific
      lymphocyte proliferative response, were reduced.

PMID- 8557471
TI  - Potentiation of ionophorous anticoccidials with dihydroquinolines: compatibility
      of lasalocid and semduramicin with duokvin.
AB  - Three battery tests were conducted to reveal whether or not there is an
      interaction between the new dihydroquinoline antioxidant, duokvin and lasalocid
      or the new anticoccidial, semduramicin, similar to that observed with some other
      ionophorous anticoccidials. In terms of body weight gain, no significant
      difference due to toxic interaction between duokvin and any dose of lasalocid or
      semduramicin was detected in chickens experimentally infected with oocysts of
      Eimeria tenella and E. mitis. Anticoccidial efficacy at reduced doses of both
      lasalocid and semduramicin in combination with duokvin showed numerical
      improvement; however, this again proved to be insignificant. The lack of
      incompatibility of this antioxidant with lasalocid or semduramicin allows their
      simultaneous administration on the one hand, but it fails to enable a substantial
      reduction of the chemoprophylactic concentration of anticoccidials in the broiler
      ration on the other.

PMID- 8557472
TI  - Concurrent infection with sibling Trichinella species in a natural host.
AB  - Random amplified polymorphic DNA (RAPD) analysis of individual Trichinella muscle
      larvae, collected from several sylvatic and domestic animals in Estonia, revealed
      concurrent infection of a racoon dog with Trichinella nativa and Trichinella
      britovi. This finding provides strong support for their taxonomic ranking as
      sibling species. These 2 species appear uniformly distributed among sylvatic
      animals through Estonia, while Trichinella spiralis appears restricted to the
      domestic habitat.

PMID- 8557473
TI  - Mitochondrial alleles of Simulium damnosum sensu lato infected with Onchocerca
      volvulus.
AB  - Onchocerca volvulus infected Simulium damnosum s.l. were analysed by directed
      heteroduplex analysis. Of 73 infected flies, 68 produced heteroduplex products
      identical to those previously identified. All 6 major sibling species, except S.
      leonense, were present in this group. In the 5 remaining flies, 2 new
      heteroduplex patterns were noted. Molecular phylogenetic analysis of these
      samples suggested that they belonged to the S. squamosum/S. yahense subcomplex.
      The ability to reliably genotype adult flies will permit studies of the vectorial
      capacity of the sibling species of S. damnosum s.l. for the blinding and non
      blinding strains of O. volvulus.

PMID- 8557474
TI  - Shedding of surface-bound antibody by adult Dictyocaulus viviparus.
AB  - Dictyocaulus viviparus-infected calves exhibit strong antibody responses to the
      surface of all stages of the parasite. To examine whether surface-bound antibody
      is released, fluorescent-labelled antibody was bound to living parasites that
      were incubated either at 37 degrees C, or in the presence of a metabolic
      inhibitor at 2 degrees C. The amount of surface-bound antibody was measured by
      quantitative fluorescence before and after incubation for 24 h. Loss of antibody
      from the parasite surface was compared in adult worms, sheathed and artificially
      exsheathed third-stage larvae (L3). Rapid reductions in fluorescence were
      observed with adult parasites maintained at 37 degrees C but this was inhibited
      by incubation at 2 degrees C in the presence of sodium azide. In contrast, there
      was no such loss from the surface of the sheathed or exsheathed L3 maintained at
      37 degrees C.

PMID- 8557475
TI  - Importance of T-cell-dependent inflammatory reactions in the decline of
      microsomal cytochrome P450 concentration in the livers of rats infected with
      Fasciola hepatica.
AB  - The concentration of cytochrome P450, measured spectrophotometrically in
      microsomal preparations from the livers of rats infected with 30 metacercariae of
      Fasciola hepatica, declined by approximately 50% at 3 weeks post-infection.
      Treatment of infected rats with the anti-inflammatory agent dexamethasone (2
      mg/kg at 48 h intervals for 8 days prior to assay) abolished the decline in P450
      content. Assay of P450 in infected congenitally athymic (nude) rats showed normal
      levels. These results demonstrate that the T-cell-dependent inflammatory response
      in the liver of the host is a necessary factor in the development of the decline
      in hepatic P450, which is known to compromise the metabolism of certain drugs in
      infected hosts.

PMID- 8557476
TI  - A prevalence study of ear problems in school children in Kiambu district, Kenya,
      May 1992.
AB  - Information on the prevalence of hearing impairment and related ear pathologies
      in children in sub-Saharan Africa is scarce. A pilot study for a clinical trial
      of simple treatments for chronic suppurative otitis media (CSOM) in school
      children in Kiambu district, Kenya, provided information on the prevalence of
      hearing impairment and ear pathologies. Five-thousand-three-hundred-sixty-eight
      children from 57 randomly chosen primary schools in Kiambu district were
      examined. Simple otoscopy was performed by clinical officers with specialty
      training in ENT, and hering testing was performed by trained nurses, using a hand
      held field audiometer. Microbiological specimens were obtained from those
      children with CSOM. Five-point-six percent of the children had a hearing
      impairment of > 30 dB HL in one or both ears, with 2.2% having bilateral hearing
      impairment. Two-point-four percent had at least one perforated tympanic membrane,
      and 1.1% had CSOM. Eight-point-six percent of the children had wax obstructing
      the tympanic membrane. There is evidence of a relationship between hearing
      impairment and both CSOM and wax obstructing the tympanic membrane. The most
      common organisms found were Pseudomonas spp. (34%), Proteus spp. (34%) and
      Eschericia coli (19%). These results are comparable with other studies in Africa
      and indicate a considerable burden of ear disease in Kiambu district, Kenya.

PMID- 8557477
TI  - Spontaneous and evoked otoacoustic emissions in pre-term and full-term neonates:
      is there a clinical application?
AB  - In neonates and infants, hearing impairment leads to impaired language and
      cognitive development. For that reason, early detection of this sensory deficit
      is of outstanding importance, particularly in pre-term neonates, who constitute a
      high risk population in regard to very early acquired hearing loss. Evoked (EOAE)
      and spontaneous otoacoustic emission (SOAE) recording in 93 pre-term and full
      term neonates revealed that this technique is potentially useful for auditory
      screening in neonatology units. EOAEs and SOAEs can be recorded successfully from
      30 weeks of conceptional age. SOAEs were found to be prevalent in females and
      presented higher peak numbers in right than in left ears. Furthermore, SOAE
      incidence in pre-term and full-term neonates was found to be high in EOAE
      positive ears, associated with strong and robust EOAEs.

PMID- 8557478
TI  - Acoustic features of normal-hearing pre-term infant cry.
AB  - Acoustic features of expiratory cry vocalizations were studied in 125 pre-term
      infants prior to being discharged from a level-3 neonatal intensive care unit.
      The purpose was to describe various phonatory behaviors in infants in whom
      significant hearing loss could be ruled out. We also compared these results with
      normal-hearing full-term infants, and evaluated whether linkage exists among
      acoustic cry features and various anthropometric, diagnostic and treatment
      variables obtained throughout the peri- and neonatal periods. Our analysis
      revealed that cry duration was significantly related to total days receiving
      respiratory assistance. The occurrence of other complex spectral and temporal
      aspects of acoustic cry vocalizations including harmonic doubling and vibrato
      also increased in infants receiving some form of respiratory assistance. The
      presence of harmonic doubling also depended on weight and conceptional age at
      test. The discussion focuses on the implication of these relationships and
      directions for future research.

PMID- 8557479
TI  - Long-term effect of perinatal and postnatal asphyxia on developing human auditory
      brainstem responses: peripheral hearing loss.
AB  - Peripheral hearing was assessed by examining brainstem auditory evoked responses
      (BAER) in children who suffered perinatal or postnatal asphyxia, particularly in
      those with residual neurodevelopmental deficits, to investigate the long-term
      effect of asphyxia on the developing auditory sensitivity. The BAER data were
      collected at least 6 months after the episode of asphyxia. Of the children who
      suffered perinatal asphyxia, hearing loss was found more frequently in those who
      exhibited residual neurodevelopmental deficits (17.1%) than in those who did not
      (6.3%), but this difference did not reach statistical significance. This implied
      that the long-term effect of perinatal asphyxia on the peripheral auditory system
      and its effect on the central nervous system may be relatively discrete or not
      closely correlated. The occurrence of hearing loss did not appear to be closely
      related to the degree of perinatal asphyxia, although hearing loss occurred more
      frequently in the children after severe asphyxia compared to those after mild
      asphyxia. There was no evidence for permanent hearing loss in the children who
      survived severe, prolonged postnatal asphyxia and exhibited residual
      neurodevelopmental deficits. These findings suggest that a critical period of
      particular sensitivity to the effect of hypoxia may exist during the development
      of the human peripheral auditory system. This period may range from some time
      prenatally to some time shortly after birth, probably the third postnatal month.
      After that, hypoxia is unlikely to lead to permanent hearing loss.

PMID- 8557480
TI  - Computer assisted pulse oximetry for detecting children with obstructive sleep
      apnea syndrome.
AB  - A prospective study was carried out on 110 children undergoing tonsillectomy or
      adenotonsillectomy to evaluate the usefulness of computer assisted pulse oximetry
      (POM) as a screening tool for nocturnal obstructive sleep apnea episodes. Twenty
      one healthy age-matched children served as a control group. A self-designed
      software (CAPO version 1.0) was used to analyse collected oximetric data. Pre
      operatively up to 25% of children showed a characteristic pattern of repeated
      oxygen desaturations related to partial or complete airway obstruction, which was
      not seen in the matched group. Thirty-one percent had an oxygen desaturation
      index (ODI) of more than 2 phases/h, being significantly higher than in the
      matched group. These children could not be identified from history or clinical
      examination with an acceptable sensitivity. A second monitoring has been
      performed in 32 patients 5 days after surgery. The nocturnal cyclic oscillations
      of oxygen saturation resolved in almost all cases. Computer assisted POM is
      useful in predicting and grading nocturnal obstruction and adds decision making
      data for the treatment in children suspected of suffering from obstructive sleep
      apnea.

PMID- 8557481
TI  - Investigation of oral alpha-streptococcus showing inhibitory activity against
      pathogens in children with tonsillitis.
AB  - The incidence of oral alpha-streptococcus with inhibitory activity against group
      A streptococcus, as a defense mechanism against bacterial infection in the oral
      cavity, was investigated in pediatric individuals with tonsillitis. Infection by
      group A streptococcus appeared to be common in children, because the detection
      rate of inhibitory alpha-streptococcus in healthy children as well as pediatric
      patients with tonsillitis was lower than in adults and elderly patients. In
      particular, the detection rate of these strains was predominantly low in patients
      with beta-streptococcus. Among pediatric patients scheduled for tonsillectomy,
      the detection rate of inhibitory alpha-streptococcus was low preoperatively.
      However, the rate was markedly increased after surgery. The high postoperative
      detection rate of these strains reflected the decreased incidence of group A
      streptococcal infection. The results of this investigation of bacterial
      interference between oral alpha-streptococcus and group A streptococcus suggested
      that surgical treatment is a more effective approach for improving the oral
      bacterial flora in children with recurrent tonsillitis.

PMID- 8557482
TI  - Nodular fasciitis of the nose in a child.
AB  - Nodular fasciitis is an unusual benign tumour composed of fibroblasts. It
      presents as a rapidly growing mass arising from subcutaneous or deep fascia. Less
      than 20% of cases occur in children. Diagnosis can only be made by
      histopathological examination of a biopsy of the lesion. A case of nodular
      fasciitis presenting as a mass arising from the right nasal cavity in a 19-month
      old female is presented. The lesion was successfully eradicated by surgical
      removal. There has been no recurrence at 4-year review. Nodular fasciitis is a
      benign condition that may mimic malignancy clinically and histologically.
      Recognition of this condition is important to avoid unnecessarily aggressive
      treatment. Relevant clinical, radiological and histological features are
      discussed.

PMID- 8557483
TI  - Neonatal choristoma of the tongue containing glial tissue: diagnosis and surgical
      considerations.
AB  - There are only six case reports documenting the presence of glial tissue in the
      tongue. Because of the small number of cases, the presentation and biologic
      behavior of these lesions is poorly characterized. We present the case of a 10
      day-old male infant who arrived at the University of Michigan Medical Center with
      a history of positional dyspnea, with resultant cyanosis and bradycardia,
      dysphagia, and a mass at the base of the tongue. Histopathologically, this lesion
      was initially labeled as a hamartoma, but was ultimately defined as a choristoma
      based on the exclusive presentation of glial tissue in the specimen. This paper
      will discuss the presentation, diagnostic evaluation, and therapeutic management
      of this case. In addition, the role of intraoperative electrodiagnostic
      monitoring to preserve neuromuscular function will be addressed.

PMID- 8557484
TI  - Aneurysmal bone cyst of the temporal bone presenting as hearing loss in a child.
AB  - We present an unusual case of a temporal bone and skull base tumor in a ten-year
      old child. The patient presented with unilateral hearing loss and headaches.
      Radiologic, surgical, and histologic findings were consistent with an aneurysmal
      bone cyst. This is the first report on this rare entity to document its
      appearance in the temporal bone and skull base using magnetic resonance imaging.
      Treatment consisted of surgical removal, cranioplasty, and reconstruction of the
      external auditory canal.

PMID- 8557485
TI  - Nuclear matrix proteins as structural and functional components of the mitotic
      apparatus.
AB  - The eukaryotic nucleus is a membrane-enclosed compartment containing the genome
      and associated organelles supported by a complex matrix of nonhistone proteins.
      Identified as the nuclear matrix, this component maintains spatial order and
      provides the structural framework needed for DNA replication, RNA synthesis and
      processing, nuclear transport, and steroid hormone action. During mitosis, the
      nucleoskeleton and associated chromatin is efficiently dismantled, packaged,
      partitioned, and subsequently reassembled into daughter nuclei. The dramatic
      dissolution of the nucleus is accompanied by the assembly of a mitotic apparatus
      required to facilitate the complex events associated with nuclear division. Until
      recently, little was known about the fate or disposition of nuclear matrix
      proteins during mitosis. The availability of specific molecular probes and
      imaging techniques, including confocal microscopy and improved immunoelectron
      microscopy using resinless sections and related procedures, has enabled
      investigators to identify and map the distribution of nuclear matrix proteins
      throughout the cell cycle. This chapter will review the structure, function, and
      distribution of the protein NuMA (nuclear matrix mitotic apparatus) and other
      nuclear matrix proteins that depart the nucleus during the interphase/mitosis
      transition to become structural and functional components within specific domains
      of the mitotic apparatus.

PMID- 8557486
TI  - The dynamic properties and possible functions of nuclear lamins.
AB  - The nuclear lamins are thought to form a thin fibrous layer called the nuclear
      lamina, underlying the inner nuclear envelope membrane. In this review, we
      summarize data on the dynamic properties of nuclear lamins during the cell cycle
      and during development. We discuss the implications of dynamics for lamin
      functions. The lamins may be involved in DNA replication, chromatin organization,
      differentiation, nuclear structural support, and nuclear envelope reassembly.
      Emphasis is placed on recent data that indicate that the lamina, contrary to
      previous views, is not a static structure. For example, the lamins form
      nucleoplasmic foci, distinct from the peripheral lamina, which vary in their
      patterns of distribution as well as their composition in a cell cycle-dependent
      manner. During the S phase, these foci colocalize with chromatin and sites of DNA
      replication. At other points during the cell cycle, they may represent sites of
      lamin post-translation processing that take place prior to incorporation into the
      lamina. Secondary modifications of the lamins such as isoprenylation and
      phosphorylation are involved in the regulation of the dynamic properties and the
      assembly of lamins. In addition, a number of lamin-associated proteins have been
      recently identified and these are described along with their potential functions.

PMID- 8557487
TI  - Intracellular structure and nucleocytoplasmic transport.
AB  - Intracellular movement of any solute or particle accords with one of two general
      schemes: either it takes place predominantly in the solution phase or it occurs
      by dynamic interactions with solid-state structures. If nucleocytoplasmic
      exchanges of macromolecules and complexes are predominantly solution-phase
      processes, i.e., if the former ("diffusionist") perspective applies, then the
      only significant structures in nucleocytoplasmic transport are the pore
      complexes. However, if such exchanges accord with the latter ("solid-state")
      perspective, then the roles of the nucleoskeleton and cytoskeleton in
      nucleocytoplasmic transport are potentially, at least, as important as that of
      the pore complexes. The role of the nucleoskeleton in mRNA transport is more
      difficult to evaluate than that of the cytoskeleton because it is less well
      characterized, and current evidence does not exclude either perspective. However,
      the balance of evidence favors a solid-state scheme. It is argued that ribosomal
      subunits are also more likely to migrate by a solid-state rather than a
      diffusionist mechanism, though the opposite is true of proteins and tRNAs.
      Moreover, recent data on the effects of viral proteins on intranuclear RNA
      processing and migration accord with the solid-state perspective. In view of this
      balance of evidence, three possible solid-state mechanisms for nucleocytoplasmic
      mRNA transport are described and evaluated. The explanatory advantage of solid
      state models is contrasted with the heuristic advantage of diffusion theory, but
      it is argued that diffusion theory itself, even aided by modern computational
      techniques and numerical and graphical approaches, cannot account for data
      describing the movements of materials within the cell. Therefore, the mechanisms
      envisaged in a diffusionist perspective cannot be confined to diffusion alone,
      but must include other processes such as bulk fluid flow.

PMID- 8557488
TI  - Toward a molecular understanding of the structure and function of the nuclear
      pore complex.

PMID- 8557489
TI  - Nuclear pore complex proteins.
AB  - The nuclear envelope forms the boundary between the nucleus and the cytoplasm and
      as such regulates the exchange of macromolecules between the two compartments.
      The channels through the nuclear envelop that actually mediate this
      macromolecular traffic are the nuclear pore complexes. These are extremely
      elaborate structures which in vertebrate cells exhibit a mass of approximately
      120 MDa. They are thought to be composed of as many as 100 distinct polypeptide
      subunits. A major challenge in the field of nucleocytoplasmic transport is to
      identify these subunits and to determine their functions and interactions in the
      context of the three-dimensional structure of the nuclear pore complex. It is the
      aim of this review to summarize what is currently known of the 20 or so nuclear
      pore complex proteins that have been described in either vertebrate or yeast
      cells.

PMID- 8557490
TI  - Targeting and association of proteins with functional domains in the nucleus: the
      insoluble solution.
AB  - The mammalian nucleus is highly organized into distinct functional domains
      separating different biochemical processes such as transcription, RNA processing,
      DNA synthesis, and ribosome assembly. A number of proteins known to participate
      in these processes were found to be specifically localized at their corresponding
      functional domains. A distinct targeting sequence, necessary and sufficient for
      the localization to DNA replication foci, was identified in the N-terminal,
      regulatory domain of DNA methyltransferase and DNA ligase I and might play a role
      in the coordination of DNA replication and DNA methylation. The fact that the
      targeting sequence is absent in lower eukaryotic and prokaryotic DNA ligase I
      homologs suggests that "targeting" is a rather recent development in evolution.
      Finally, targeting sequences have also been identified in some splicing factors
      and in viral proteins, which are responsible for their localization to the
      speckled compartment and to the nucleolus, respectively. These higher levels of
      organization are likely to contribute to the regulation and coordination of the
      complex and interdependent biochemical processes in the mammalian nucleus.

PMID- 8557491
TI  - Nuclear matrix acceptor binding sites for steroid hormone receptors: a candidate
      nuclear matrix acceptor protein.
AB  - Steroid/nuclear-hormone receptors are ligand-activated transcription factors that
      have been localized to the nuclear matrix. The classic model of hormone action
      suggests that, following activation, these receptors bind to specific "steroid
      response elements" on the DNA, then interact with other factors in the
      transcription initiation complex. However, evidence demonstrates the existence of
      specific chromatin proteins that act as accessory factors by facilitating the
      binding of the steroid receptors to the DNA. One such protein, the "receptor
      binding factor (RBF)-1", has been purified and shown to confer specific, high
      affinity binding of the progesterone receptor to the DNA. Interestingly, the RBF
      1 is localized to the nuclear matrix. Further, the RBF-1 binds specifically to a
      sequence of the c-myc proto-oncogene that has the appearance of a nuclear matrix
      attached region (MAR). These results, and other findings reviewed here, suggest
      that the nuclear matrix is involved intimately in steroid hormone-regulated gene
      expression.

PMID- 8557492
TI  - Nuclear matrix and the cell cycle.
AB  - The facts that the nuclear matrix represents a structural framework of the cell
      nucleus and that nuclear events, such as DNA replication, transcription, and DNA
      repair, are associated with this skeletal structure suggest that its components
      are subject to cell cycle-regulatory mechanisms. Cell cycle regulation has been
      shown for nuclear lamina assembly and disassembly during mitosis and chromatin
      reorganization. Little attention has so far been paid to internal nuclear matrix
      proteins and matrix-associated proteins with respect to the cell cycle. This
      survey attempts to summarize available data and presents experimental evidence
      that important metabolic functions of the nucleus are regulated by the transient,
      cell cycle-dependent attachment of enzymes and regulatory proteins to the nuclear
      matrix. Results on thymidine kinase and RNA polymerase during the synchronous
      cell cycle of Physarum polycephalum demonstrate that reversible binding to the
      nuclear matrix represents an additional level of regulation for nuclear
      processes.

PMID- 8557493
TI  - Specificity and functional significance of DNA interaction with the nuclear
      matrix: new approaches to clarify the old questions.
AB  - In this chapter the specificity of chromosomal DNA partitioning into topological
      loops is discussed. Different experimental approaches used for the analysis of
      the above problem are critically reviewed. This discussion is followed by
      presentation of a novel approach for mapping the DNA loop anchorage sites that we
      have developed. This approach, based on the excision of the whole DNA loops by
      topoisomerase II-mediated DNA cleavage at matrix attachment sites, seems to
      constitute a unique tool for the analysis of topological organization of
      chromosomal DNA in living cells. We also discuss experimental results indicating
      that the DNA-loop anchorage sites form "weak points" in chromosomes that are
      preferentially sensitive to cleavage with both endogenous and exogenous
      nucleases. In connection with this discussion, rationales for the supposition
      that DNA loops constitute basic units of eukaryotic genome organization and
      evolution are considered. The chapter concludes by suggesting a new model of
      spatial organization of eukaryotic genome within the cell nucleus that resolves
      apparent contradictions between different data on the specificity of DNA
      interaction with the nuclear matrix.

PMID- 8557494
TI  - Nuclear matrix isolated from plant cells.
AB  - Residual nuclear matrices can be successfully obtained from isolated nuclei of
      different monocot and dicot plant species using either high ionic or low ionic
      extraction protocols. The protein composition of isolated nuclear matrices
      depends on the details of isolation protocols. They are stable and present in all
      cases, a tripartite organization with a lamina, nucleolar matrix, and internal
      matrix network, and also maintain some of the basic architectural features of
      intact nuclei. In situ preparations demonstrate the continuity between the
      nuclear matrix and the plant cytoskeleton. Two-dimensional separation of isolated
      plant nuclear matrix proteins reveals a heterogeneous polypeptide composition
      corresponding rather to a complex multicomponent matrix than to a simple
      nucleoskeletal structure. Immunological identification of some plant nuclear
      matrix components such as A and B type lamins, topoisomerase II, and some
      components of the transcription and splicing machineries, internal intermediate
      filament proteins, and also specific nucleolar proteins like fibrillarin and
      nucleolin, which associate to specific matrix domains, establish a model of
      organization for the plant nuclear matrix similar to that of other eukaryotes.
      Components of the transcription, processing, and DNA-anchoring complexes are
      associated with a very stable nucleoskeleton. The plant matrix-attached regions
      share structural and functional characteristics with those of insects,
      vertebrates, and yeast, and some of them are active in animal cells. In
      conclusion, the available data support the view that the plant nuclear matrix is
      basically similar in animal and plant systems, and has been evolutionarily
      conserved in eukaryotes.

PMID- 8557495
TI  - Origin of posterior pituitary high intensity on T1-weighted magnetic resonance
      imaging. Immunohistochemical, electron microscopic, and magnetic resonance
      studies of posterior pituitary lobe of dehydrated rabbits.
AB  - RATIONALE AND OBJECTIVES: To investigate the origin of posterior pituitary high
      intensity (PPHI) seen on T1-weighted magnetic resonance (MR) images. METHODS: Six
      rabbits, including four rabbits deprived of drinking water for 4 days and two
      control rabbits, were examined by MR imaging. Plasma vasopressin levels were
      sequentially measured by radioimmunoassay. Pituitary glands were immunostained
      with guinea pig anti-rabbit vasopressin antibody, and ultrathin sections of
      Epon/Araldite-embedded specimens were observed with a transmission electron
      microscope. RESULTS: In control rabbits, PPHI was noted on T1-weighted MR images,
      and the posterior pituitary lobe was positively immunostained with anti
      vasopressin antibody. At the ultrastructural level, nerve terminals contained
      numerous neurosecretory granules bearing vasopressin. Conversely, plasma
      vasopressin levels gradually increased and PPHI was absent in 4-day dehydrated
      rabbits. The posterior lobe was scarcely stained with anti-vasopressin antibody,
      and neurosecretory granules were rarely observed. However, a number of small
      dispersed vesicles, possibly derived from the fragmentation of neurosecretory
      granule envelopes, were seen in the nerve terminal. CONCLUSIONS: Posterior
      pituitary high signal seen on T1-weighted MR images is attributed to
      neurosecretory granules bearing vasopressin.

PMID- 8557496
TI  - Comparison of gadolinium-DTPA and polylysine-gadolinium-DTPA--enhanced magnetic
      resonance imaging of hepatocarcinoma in the rat.
AB  - RATIONALE AND OBJECTIVES: To compare the magnetic resonance (MR) imaging
      characteristics of gadolinium-DTPA (Gd-DTPA), a low-molecular-weight contrast
      agent, and polylysine-Gd-DTPA, a macromolecular contrast agent, in two types of
      hepatocarcinomas (HCC) in the rat. METHODS: T1-weighted spin-echo images were
      obtained in 13 rats with chemically induced HCC and 26 rats with Novikoff HCC
      before and 3 minutes to 60 hours after administration of either Gd-DTPA or
      polylysine-Gd-DTPA. RESULTS: Three minutes after polylysine-Gd-DTPA
      administration, the tumor-to-liver contrast of the two types of HCC increased
      significantly (positive contrast for chemically induced HCC and negative contrast
      for Novikoff HCC). At 30 minutes and 60 hours, the tumor-to-liver contrast
      remained above baseline values in chemically induced HCC and returned
      progressively to baseline values in Novikoff HCC. No significant increase in
      tumor-to-liver contrast was observed after Gd-DTPA administration. CONCLUSIONS:
      These results suggest that polylysine-Gd-DTPA provides a higher and more
      prolonged increase in tumor-to-liver contrast than Gd-DTPA.

PMID- 8557497
TI  - Breast infection. Mammographic and sonographic findings with clinical
      correlation.
AB  - RATIONALE AND OBJECTIVES: To characterize the mammographic, sonographic, and
      clinical findings of breast infection and to determine characteristics that could
      help differentiate it from inflammatory breast carcinoma. METHODS: The
      mammograms, sonograms, and clinical records of 21 consecutive patients who had
      mammography or sonography within 48 hours of presenting with breast infection
      were retrospectively reviewed. To exclude other causes of breast inflammation,
      patients were required to have histologic or aspiration results specific for
      infection. RESULTS: Twelve of 19 (63%) mammograms were abnormal. Mammographic
      abnormalities included an irregular mass (6; 32%), focal asymmetric density (2;
      11%), diffuse asymmetric density (2; 11%), circumscribed mass (1; 5%), and
      architectural distortion (1; 5%). Mammographic skin thickening, present in four
      (21%) patients, was focal in three and diffuse in one patient with primary breast
      Mycobacterium tuberculosis infection. No abnormally dense lymph nodes were
      demonstrated. There was no abnormal soft tissue gas. All 11 (100%) sonograms
      showed heterogeneous masses that contained internal echoes, 5 of these in
      patients who had normal mammograms. All 21 patients presented with clinical
      abnormalities, including palpable mass (20; 95%), pain (11; 52%), erythema (11;
      52%), warmth (7; 33%), skin thickening or fixation (4; 19%), and breast swelling
      (3; 14%). One patient was lactating. CONCLUSIONS: Mammographic, sonographic, and
      clinical abnormalities were usually present with breast infection that could
      mimic inflammatory carcinoma. However, diffuse mammographic skin thickening,
      edema, and dense lymph nodes were rare, and when present may prospectively
      suggest carcinoma or an unusual infection. Early surgical consultation is
      advised.

PMID- 8557498
TI  - Comparison of quantitative methods for brain single photon emission computed
      tomography analysis in head trauma and stroke.
AB  - RATIONALE AND OBJECTIVES: In this study, three semi-automated (SA) methods for
      brain single photon emission computed tomography (SPECT) analysis were evaluated
      and compared with a quantitative manual (QM) method that allowed precise
      demarcation of telencephalic and cerebellar regions of interest. METHODS: Twenty
      patients with traumatic brain injury or stroke were imaged by SPECT after
      injection of 30 mCi (1110 MBq) of Tc-99m HMPAO: The SA methods included: 1) SA
      left-to-right ratio method, which generated uptake ratios in 4 pairs of symmetric
      brain sectors in each slice; 2) adjusted scale method, which displayed each slice
      according to a linear 10-color scale; and 3) SA brain-to-cerebellum ratio method,
      which exhibited a color scale indicating 5% change in the ratio. RESULTS: The
      concordance with QM method was 85% for the adjusted scale method and 80% for the
      SA left-to-right ratio method. A combination of the Adjusted Scale Method and SA
      left-to-right ratio method yielded concordant results with the QM method in 95%
      of patients. Brain-to-cerebellum ratio method gave inconsistent findings because
      of variable cerebellar activity. CONCLUSIONS: Semi-automated methods reliably
      evaluated relative brain perfusion in most patients. Whereas the adjusted scale
      method had the best correlation with the QM method, a combination of the adjusted
      scale method and SA left-to-right ratio method ws the most useful for routine
      analysis of brain perfusion. Semi-automated brain-to-cerebellum ratio method was
      found to be the least useful because of variability of cerebellum uptake,
      particularly when the brain uptake was higher than the cerebellum. The QM method
      allowed precise and most accurate delineation of regions of interest for
      quantitation of relative brain perfusion but required considerable operator input
      and knowledge of brain anatomy.

PMID- 8557499
TI  - Comparison of magnetic resonance imaging methods for examinations of abdominal
      aortic aneurysms.
AB  - RATIONALE AND OBJECTIVES: Different magnetic resonance imaging techniques were
      compared with respect to available anatomic information regarding abdominal
      aortic aneurysms (AAA) and regions involved in thrombosis. METHODS: Twenty
      patients with AAA were examined by turbo spin-echo (TSE) imaging of coronal and
      transverse slices, resulting in black blood images. Bright blood imaging was
      performed using a spoiled gradient-echo sequence with gradient moment nulling.
      Sets of 25 to 50 thin slices were recorded sequentially in a single slice mode
      using coronal and transverse orientation. Both sets of bright blood images were
      reconstructed by maximum intensity projection. RESULTS: In all patients, the size
      and shape of the AAA could better be assessed by the TSE images than by the
      gradient-echo images. In contrast, reliable differentiation of thrombotic areas
      and of the perfused lumen was possible in only 56% of the slices recorded by TSE
      imaging but in 94% of the gradient-echo images. The two-dimensional inflow
      technique provided clearly higher sensitivity even to slow blood flow than TSE
      imaging. Maximum intensity projection reconstructions from sets of coronal two
      dimensional inflow images often did not depict the lower part of the AAA because
      of saturation effects, whereas sets of transverse slices provided complete
      angiograms of the aortoiliac vascular tree. DISCUSSION: At this time, no single
      magnetic resonance method can provide all essential information. A comprehensive
      examination should include TSE imaging for topographic assessment and transverse
      two-dimensional inflow imaging for analysis of thrombotic areas.

PMID- 8557500
TI  - Cellular uptake and trafficking of a prototypical magnetic iron oxide label in
      vitro.
AB  - RATIONALE AND OBJECTIVES: Target-specific magnetic resonance (MR) contrast agents
      are being developed to improve the accuracy of MR imaging. The purpose of this
      study was to determine the mechanism of cell uptake, and modes of intracellular
      trafficking of a prototypical iron oxide label (RMA) used in the synthesis of
      some target-specific MR contrast agents. METHODS: The prototypical agent (RMA)
      consisted of a dextran-coated monocrystalline iron oxide that was modified with
      rhodamine (fluorescent label) and opsonized with albumin. Fluorescence microscopy
      was performed in a phagocytic C6 cell line and in murine bone marrow macrophages.
      Immunohistochemistry against lysosomal markers was used to confirm the
      intracellular location of the label. RESULTS: RMA was identified inside cells
      after incubation at concentrations as low as 4.0 x 10(-10) M Fe, typically
      observed with receptor mediated endocytosis and several orders of magnitude lower
      than that expected with fluid phase pinocytosis. Cell uptake could be inhibited
      by excess protein but not by dextran. RMA localized initially to tubular and to
      round intracellular organelles and co-localized with an antibody against a murine
      lysosomal glycoprotein antibodies (LGP-A) in macrophages. Three days after
      incubation, RMA was concentrated in perinuclear vesicles, which most likely
      represent terminal lysosomes where final breakdown appears to occur. CONCLUSIONS:
      The mechanism of cellular uptake of a prototypical opsonized iron oxide label is
      consistent with receptor-mediated endocytosis. Immediately after cell contact,
      RMA localizes to the lysosomal compartment and at long time points reside in
      vesicles that by morphology and distribution appear to be terminal lysosomes.
      Iron oxides therefore demonstrate metabolism via the lysosomal pathway.

PMID- 8557501
TI  - A toxicologic risk for using manganese complexes? A literature survey of existing
      data through several medical specialties.
AB  - This article summarizes data from the literature about biologic functions,
      toxicity, and biokinetics of manganese to help the reader assess the importance
      of complex stability of manganese-based contrast agents. Free manganese may
      present a greater risk than free gadolinium, especially because it has a
      physiologic role and can therefore trigger multiple functions. Of particular
      interest are the deleterious effects of manganese on the central nervous system
      (it can cross the intact blood-brain barrier) and on developing life (it
      penetrates the placental barrier as well and is teratogenic). After intravenous
      contrast injection, normal (enteral) regulation mechanisms for manganese
      homeostasis are bypassed, and there is a danger of individual overdosing. Excess
      manganese, for example in patients with chronic liver disease or with chronic
      parenteral nutrition, has already been detected by magnetic resonance imaging in
      the basal ganglia and was found to coincide with neurologic symptoms.
      Decomplexation with release of free manganese substantially prolongs the
      elimination of the metal because manganese can be excreted only slowly via the
      biliary system. This may be of particular importance in patients with impaired
      hepatic function. Although minimal amounts of free manganese ions are not
      considered harmful to the human body, significant decomplexation of manganese
      complexes will require careful analysis of the diagnostic benefit versus the
      potential risk posed by the free metal ions.

PMID- 8557502
TI  - Temporal patterns of uncoupling between oxidative metabolism and regional
      cerebral blood flow demonstrated by functional magnetic resonance imaging.
AB  - RATIONALE AND OBJECTIVES: Brain activation can be detected by functional magnetic
      resonance imaging. Termination of stimulation can cause drop of postactivation
      signal below preactivation baseline; the nature of this "undershoot" remains
      controversial. The authors investigated postactivation signal after stimulation
      of the visual cortex with photic stimuli of different duration. METHODS:
      Activation of visual cortex in 11 healthy subjects was studied. The authors
      underwent short and long stimulation. The relation between activation and
      postactivation signal was investigated after both durations of stimulation.
      RESULTS: Average postactivation signal after short stimulation was -1.71 +/-
      2.66% and after long stimulation 0.82 +/- 1.59% (P < or = 0.01). Significant
      "undershoot" was detected after short stimulation in the majority of cases,
      although this was typically absent after long stimulation. CONCLUSIONS: The
      authors propose that "undershoot" is caused by decreased oxygen content in venous
      blood compared with the preactivation level and may reflect increased extraction
      of oxygen as a result of glycolytic metabolism. The absence of "undershoot" after
      longer stimulation suggests a gradual shift from uncoupling between regional
      cerebral blood flow and oxygen consumption toward a steady state.

PMID- 8557503
TI  - Efficacy of gadolinium administration in magnetic resonance imaging screening of
      patients with complex partial seizures and results of a normal neurologic
      examination.
AB  - RATIONALE AND OBJECTIVES: Magnetic resonance imaging has become a standard
      screening tool in the evaluation of patients with complex partial seizures. This
      study prospectively addresses the efficacy, if any, of routinely adding
      gadolinium-enhanced images to routine T2-weighted images in patients with a
      normal neurologic examination. METHODS: One hundred consecutive patients with
      electroencephalogram and clinical evidence of complex partial seizures and no
      other neurologic abnormalities were examined prospectively with axial and coronal
      T2-weighted spin-echo images, followed by axial and coronal gadolinium-enhanced
      T1-weighted scans. RESULTS: The scans in 73 patients were interpreted as normal,
      14 had nonspecific white matter lesions, 5 had asymmetry of the temporal horns,
      and 2 had asymmetric signal intensity in the temporal lobes, and the scans in 6
      showed abnormal gadolinium enhancement. Of the lesions in the six patients whose
      scans showed abnormal enhancement, four were seen well on the T2-weighted images.
      Of the remaining two, one was a small cerebellar venous angioma, and the other, a
      probable tiny convexity meningioma. One temporal lobe glioma seen on the T2 scans
      did not enhance with gadolinium. CONCLUSIONS: Routine administration of
      gadolinium does not appear to be of benefit in imaging patients with complex
      partial seizures who are otherwise neurologically normal.

PMID- 8557504
TI  - Role of high-resolution magnetic resonance imaging for differentiating melanin
      containing skin tumors.
AB  - RATIONALE AND OBJECTIVES: The aim of the study was to evaluate the use of high
      resolution magnetic resonance imaging (MRI) for differentiation of melanin
      containing skin tumors. METHODS: Twenty-seven melanocytic nevi and 18 malignant
      melanomas were examined by high resolution MRI. Signal intensities and signal-to
      noise (SNR) and contrast-to-noise ratios (CNR) of the tumors were determined in
      enhanced (T1, T2, water-suppression, and fat-suppression sequences) and contrast
      enhanced images (T1 and fat-suppression sequences). The differences were tested
      for significance by a Wilcoxon test. RESULTS: Malignant melanomas differed from
      melanocytic nevi in that they displayed a higher SNR in T2-weight and unenhanced
      and contrast-enhanced fat-suppression scan. Malignant melanomas exhibited a
      higher CNR than did benign lesions in unenhanced and contrast-enhanced fat
      suppression sequences with dermis as reference tissue (P < 0.05) and in enhanced
      fat-suppression sequences with subcutis as reference tissue (P < 0.05).
      CONCLUSIONS: The usefulness of SNR and CNR analysis on MRI for the
      differentiation of malignant skin tumors from benign skin tumors of the melanin
      containing system is limited. Clinical and histologic examinations are, further,
      the important step in evaluation of melanin-containing skin tumors.

PMID- 8557505
TI  - Evaluation of gadobutrol in a rabbit model as a new lanthanide contrast agent for
      computed tomography.
AB  - RATIONALE AND OBJECTIVES: The efficacy of the neutral lanthanide contrast agent
      gadobutrol was compared to that of the iodinated contrast agent iopromide in
      rabbits. METHODS: The computed tomography (CT) attenuation of increasing
      concentrations of gadolinium (Gd) (gadobutrol) and iodine (I) (iopromide) was
      measured in Hounsfield units (HU) in aqueous solution at 80, 120, and 137 kV. The
      peak enhancement (net increase in CT attenuation compared with baseline) and the
      time-enhancement product in the aorta and in the renal parenchyma of the outer
      and inner cortex were measured in rabbits over a 5-minute period after the
      animals were given single intravenous injections of 0.7, 1.0, and 1.5 mmol Gd/kg
      of gadobutrol and 1.0 and 2.4 mmol I/kg of iopromide. RESULTS: In vitro, the CT
      attenuation of gadolinium was 40% higher than that of iodine at equivalent mass
      concentrations (120 kV). The mean peak enhancements in the aorta after the
      injections of 0.7, 1.0, and 1.5 mmol Gd/kg and 1.0 and 2.4 mmol I/kg were 216,
      313, 591, 224, and 498 HU, respectively. In addition, a 30-second injection of
      the high dose of gadobutrol resulted in an attenuation profile that was suitable
      for a three-dimensional reconstruction of the aorta and the renal vasculature.
      CONCLUSIONS: Because of the higher CT attenuation of gadolinium compared with
      that of iodine, the neutral macrocyclic chelate gadobutrol is a more effective
      contrast agent than iopromide for CT at lower doses of the imaging atom.

PMID- 8557506
TI  - Dynamic contrast-enhanced magnetic resonance imaging of the breast combined with
      pharmacokinetic analysis of gadolinium-DTPA uptake in the diagnosis of local
      recurrence of early stage breast carcinoma.
AB  - RATIONALE AND OBJECTIVES: This study was designed to assess the efficacy of
      dynamic contrast-enhanced magnetic resonance imaging (MRI) of the breast combined
      with pharmacokinetic analysis of gadolinium (Gd)-DTPA uptake in the diagnosis of
      local recurrence of early stage breast carcinoma. METHODS: Fifty women treated
      with breast-conserving surgery and radiotherapy underwent breast MRI. Dynamic
      magnetic resonance data obtained at four preselected slice locations were
      analyzed to examine Gd-DTPA uptake based on a pharmacokinetic model using three
      parameters: wash-in rate, wash-out rate, and amplitude of uptake. Synthetic
      images were produced from the above parameters and their derivatives--maximum
      uptake and reciprocal of half the time to maximum. For each region of interest
      (ROI), median parameter values were calculated. The mean pixel signal intensity
      of each ROI was plotted against time, and an enhancement index was determined.
      RESULTS: Sixty ROIs were selected: 49 lesions were benign, and 11, malignant.
      Significant differences between benign and malignant lesions were found for the
      enhancement index (P < 0.0001), maximum uptake (P < 0.0001), amplitude of uptake
      (P < 0.0001), wash-in rate (P = 0.03), wash-out rate (P = 0.01), and the
      reciprocal of half the time to maximum (P = 0.0005). The respective sensitivities
      and specificities were as follows: for the enhancement index, 1.00 and 0.96; for
      maximum uptake, 1.00 and 0.96; for amplitude of uptake, 0.91 and 0.94; for wash
      in rate 0.82 and 0.47; for wash-out rate 0.91 and 0.59; and for the reciprocal of
      half the time to maximum, 1.00 and 0.51. CONCLUSIONS: Dynamic scanning proved
      essential for the detection and differential diagnosis of local tumor recurrence.
      Pharmacokinetic analysis of Gd-DTPA uptake can be used to produce parametric
      images that retain the spatial resolution of the original images while providing
      additional information about lesion permeability and vascularity, and helping to
      avoid the observer variability associated with ROI analysis.

PMID- 8557507
TI  - Adverse effects of calcium binding contrast agents in diagnostic cardiac
      angiography. A comparison between formulations with and without calcium binding
      additives.
AB  - RATIONALE AND OBJECTIVES: The authors compared complications and hemodynamic and
      electrophysiologic effects of two formulations of diatrizoate, one with additives
      that bind calcium and one without, in diagnostic cardiac angiography. METHODS:
      Two hundred twenty-three consecutive low-risk patients alternately received
      Hypaque 76 (group 1, little calcium binding effect), and MD 76 (group 2,
      significant calcium binding). Electrocardiographic and hemodynamic changes
      related to coronary angiography and left ventriculography were measured, and
      complications requiring treatment were recorded. RESULTS: There were more
      complications in patients in group 2 than in group 1 (18 versus 8, P = 0.04).
      Arterial pressure fell more, the QT interval increased more, and the heart rate
      fell more in group 2 after coronary angiography. CONCLUSIONS: Formulations of
      diatrizoate that minimize calcium binding are advocated for cardiac angiography
      when using high osmolality contrast media. The more detrimental effects that
      calcium binding has on myocardial function and cardiac conduction may lead to the
      higher incidence of complications.

PMID- 8557508
TI  - A quantitative physiologic model of blood oxygenation for functional magnetic
      resonance imaging.
AB  - RATIONALE AND OBJECTIVES: Variations in venous deoxyhemoglobin levels in response
      to neuronal activation represent a complex interplay between focal changes in
      cerebral blood flow (CBF), cerebral blood volume (CBV), and regional metabolism.
      The authors present a mathematic model that characterizes the response of venous
      oxygenation to changes in these variables. METHODS: Using a mass balance
      approach, the equations for a simple input-output model are derived and solved
      using Matlab. Changes in blood oxygenation are related to available results from
      functional magnetic resonance imaging experiments. RESULTS: Increases in CBF
      produce declines in oxygen extraction fraction and venous deoxyhemoglobin
      according to Fick's law, and are quantitatively in agreement with available
      magnetic resonance and positron-emission tomography data. A flow-volume envelope
      defines the changes in CBF relative to CBV. CONCLUSIONS: It is possible to obtain
      a quantitative understanding of changes in blood oxygenation and to relate these
      changes to the observed dynamics of magnetic resonance signal change in the
      setting of functional stimulation.

PMID- 8557509
TI  - Local and systemic effects of water-soluble contrast media and barium in rats
      with chronic small bowel obstruction.
AB  - RATIONALE AND OBJECTIVES: The local effects on the small intestine and systemic
      changes produced by different contrast media in small bowel obstruction, with
      time courses of 4 days, were evaluated. MATERIALS AND METHODS: Four groups, each
      with 10 normal rats and another four groups (also each with 10 rats) that had
      ligation of the terminal ileum (obstructed rats) for 4 days were given 3 mL of
      barium, meglumine sodium diatrizoate, iohexol, or saline (control animals).
      Radiographs were taken immediately, 1 and 4 hours after administration of
      contrast media. Immediately before sacrifice, blood samples were taken to
      determine the hematocrit (Hct), hemoglobin (Hb), white blood cell count (WBC),
      red blood cell count (RBC), and serum sodium, and potassium and chloride
      concentrations. Specimens of small bowel were taken for histologic and
      morphometric analysis. RESULTS: In obstructed rats, the image quality with
      iohexol improved on final radiographs despite being diluted in the great
      intestinal contents. There was an improvement in the serum electrolyte
      concentrations in the obstructed animals that were given any one of the contrast
      media, the best improvement being in the iohexol groups. A shortening of the
      length of epithelial cells when any one of the contrast media was administered
      was observed, as was an increase in the lymphatic space area in the diatrizoate
      group in normal rats. In the bowel proximal to the obstruction, the lymphatic
      space area was increased in the diatrizoate group and the size of the epithelial
      cells was higher in the diatrizoate and iohexol groups compared to the barium and
      saline groups. CONCLUSION: Our results suggest that iohexol offers good
      radiologic efficacy and excellent systemic and local tolerance in small bowel
      obstruction.

PMID- 8557510
TI  - BR1: a new ultrasonographic contrast agent based on sulfur hexafluoride-filled
      microbubbles.
AB  - RATIONALE AND OBJECTIVES: The basic characteristics of BR1, a novel echo contrast
      agent based on stabilized sulfur hexafluoride (SF6) microbubbles have been
      evaluated. METHODS: The authors determined the physicochemical properties (bubble
      concentration, bubble size distribution, resistance to pressure, and stability)
      and the acoustic properties (backscatter and attenuation coefficients) of BR1.
      The diagnostic value of BR1 was evaluated further in minipigs. Left heart images
      were recorded before and after injection of different doses of BR1. RESULTS: BR1
      is formulated as a lyophilized product, which after addition of saline, provides
      a suspension containing 2 x 10(8) SF6 microbubbles/mL with a number mean diameter
      of 2.5 microns. More than 90% of the bubbles are below 8 microns. The use of SF6
      rather than air provides an improved resistance to pressure increases such as the
      ones occuring in the left heart during systole. After reconstitution, the
      echogenicity and the bubble characteristics are unchanged for more than 8 hours.
      The high echogenicity remains almost constant over the entire medical frequency
      range (1-10 MHz). BR1 injections in animals resulted in a homogenous, dose
      dependent opacification of the left heart. CONCLUSIONS: Considering its high
      echogenicity, outstanding stability, and resistance to pressure changes, BR1 is a
      very promising ultrasound contrast agent.

PMID- 8557511
TI  - Small hepatocellular carcinomas undetected on two-phased incremental computed
      tomography. Angiographic and clinicopathologic findings.
AB  - RATIONALE AND OBJECTIVES: To elucidate the characteristic clinicopathologic
      features of hepatocellular carcinomas (HCCs) undetected on two-phased incremental
      computed tomography (CT). METHODS: Computed tomographic scans of 115 surgically
      resected small (< or = 3 cm) HCCs from 83 patients were performed 45 seconds and
      6 minutes after the administration of contrast material. These scans were
      compared with corresponding angiographic and histopathologic findings. RESULTS:
      Eighty HCCs (70%) were depicted on the early images; 73 (63%) on the delayed
      images; and 89 (77%) using two-phased incremental CT. The small HCCs undetected
      on the early images but seen histologically had the following characteristics:
      (1) absence of a fibrous capsule, (2) well-differentiated tumor, (3) replacing
      growth patterns of the tumors, (4) lack of fatty metamorphosis and/or clear cell
      changes, (5) hypovascular on angiography. Those not seen on delayed images had
      the following characteristics: (1) absence of a fibrous capsule, (2) replacing
      growth patterns, and (3) presence of portal tracts in the tumors. CONCLUSIONS:
      The replacing growth pattern and the presence of portal tracts correlate with the
      undetectability on CT. For HCCs undetected on CT, treatment methods must be
      considered carefully, because the HCCs may be receiving transsinusoidal and
      portal blood supplies.

PMID- 8557512
TI  - Quantitative analysis of the plain radiographic appearance of eosinophilic
      granuloma.
AB  - RATIONALE AND OBJECTIVES: To quantitate features that distinguish the plain
      radiographic appearance of eosinophilic granuloma (EG) from other solitary
      lesions of bone. MATERIALS AND METHODS: Seven hundred nine focal bone lesions,
      including 26 EGs, were analyzed according to demographic, anatomic, and plain
      radiographic features. Vector analysis of groups of features was performed to
      determine those that are most sensitive and specific for the appearance of EG in
      contrast to other lesions in the data base. RESULTS: The radiographic appearance
      of EGs was most consistently that of a medullary based lytic lesion (100%) with
      geographic destruction (76.9%), lobular contour (73.1%), and well-defined edges
      (73.1%). Long bone lesions showed these features more frequently than EGs in
      other locations. Periosteal reaction was visible in all long bone lesions but in
      only one nonlong bone lesion (5.9%). Characterization of EG in long bones as a
      lytic, medullary-based metaphyseal or diaphyseal lesion with geographic
      destruction, lobular contours, periosteal reaction, no matrix, and no
      subarticular extension showed a sensitivity of 55.6% of EG and prevalence of
      22.7%. The vector analysis-generated differential diagnoses include unicameral
      bone cyst, aneurysmal bone cyst, giant cell tumor, Brodie's abscess, enchondroma,
      chondrosarcoma, and malignant fibrous histiocytoma. CONCLUSIONS: The radiographic
      appearance of EG is relatively nonspecific but, using vector analysis, can be
      better elucidated than in current textbook descriptions.

PMID- 8557513
TI  - Quantitative analysis of the plain radiographic appearance of nonossifying
      fibroma.
AB  - RATIONAL AND OBJECTIVES: To quantitate radiographic features that distinguish the
      plain radiographic appearance of nonossifying fibroma (NOF) from other solitary
      lesions of bone. MATERIALS AND METHODS: Seven hundred nine cases of focal bone
      lesions, including 34 NOFs, were analyzed according to demographic, anatomic, and
      plain radiographic features. Vector analysis of groups of features was performed
      to determine those that are most sensitive and specific for the appearance of NOF
      in contrast to other lesions in the data base. RESULTS: The radiographic
      appearance of NOFs was most consistently a medullary based (97%), lytic lesion
      (100%) with geographic bone destruction (100%), marginal sclerosis (97%), and
      well-defined edges (94%). A statistically significant number of lesions were
      located in the distal aspect of long bones. Unicameral bone cyst shared the most
      radiographic features with the NOF. Vector analysis showed a large degree of
      overlap between NOF and other lesions such as aneurysmal bone cyst, chondromyxoid
      fibroma, and eosinophilic granuloma. The description that optimized sensitivity
      and prevalence for detection of NOF is a medullary based, ovoid lesion in the
      distal or proximal portions of a long bone with well-defined edges, a partial or
      complete rind of sclerosis, and absence of fallen fragment, periosteal reaction,
      and cortical disruption. CONCLUSION: The radiographic appearance of NOF is
      relatively nonspecific but, using vector analysis, can be better elucidated over
      current textbook descriptions.

PMID- 8557514
TI  - Antral nodularity, fold thickness, and narrowing. Signs on the upper
      gastrointestinal series that may indicate chronic active gastritis secondary to
      Helicobacter pylori.
AB  - RATIONALE AND OBJECTIVES: The purpose of this retrospective study was to
      investigate any association between the classic radiographic findings of
      nonerosive gastritis on the upper gastrointestinal (GI) series (antral
      nodularity, fold thickening, and narrowing) and histologically proven gastritis
      secondary to Helicobacter pylori. METHODS: The authors reviewed the
      histopathologic results of 31 patients who had upper GI barium examinations with
      the findings listed above who presented with dyspepsia. These patients were
      compared with 30 dyspeptic patients who had radiographically normal antrums.
      RESULTS: Twenty (64.5%) patients had chronic active gastritis and tested positive
      for H pylori organism, 5 (16.1%) were normal, 5 (16.1%) had inflammation but were
      negative for H pylori, and 1 (3.2%) had an insufficient amount of tissue. The
      barium upper GI series was 66.7% sensitive and 69.4% specific for chronic active
      gastritis secondary to H pylori (P = 0.0002 Fisher's exact test), with a positive
      predictive value of 64.5% and a negative predictive value of 83.3%. CONCLUSIONS:
      The differential diagnosis for antral nodularity, fold thickening, and narrowing
      is extensive. However, because of the common histopathologic diagnosis of chronic
      active gastritis secondary to H pylori in patients with these radiographic
      findings, the radiologist must remember to include this infectious cause of
      gastritis in the interpretive report. If the antrum is normal on the upper GI
      series, other causes should be considered.

PMID- 8557515
TI  - Detectability of early brain meningitis with magnetic resonance imaging.
AB  - RATIONALE AND OBJECTIVES: The ability of high-field (1.5 T) magnetic resonance
      imaging (MRI) to detect early brain meningitis was evaluated in a canine model.
      Contrast dose, timing postinjection, and imaging technique (specifically the use
      of magnetization transfer) were assessed. METHODS: Imaging of five canines was
      performed at 1.5 T 24 hours after injection of Cowans staphylococcus into the
      cisterna magna. Two control animals also were imaged using the same protocol,
      with one animal receiving a cisternal injection of nutrient broth only and the
      other no injection. Contrast doses of 0.1, 0.3, and 0.8 mmol/kg gadoteridol (Gd
      HP-DO3A or Pro-Hance) were compared. Scans were performed at 2, 12, and 22
      minutes after an initial injection of 0.1 mmol/kg. At each time point, paired T1
      weighted scans with and without magnetization transfer (MT) were acquired. Thirty
      minutes after the initial injection of contrast, a supplemental dose of 0.2
      mmol/kg was given (for a cumulative dose of 0.3 mmol/kg). Scans were then
      repeated at 2, 12, and 22 minutes after this dose was administered. A second
      supplemental contrast injection of 0.5 mmol/kg (for a cumulative dose of 0.8
      mmol/kg) was given at 70 minutes, and immediate postinjection scans with and
      without MT were acquired. RESULTS: In the animals receiving a cisternal injection
      of bacteria, the degree of meningeal enhancement was greatest at 0.8 mmol/kg,
      intermediate at 0.3 mmol/kg, and least at 0.1 mmol/kg. These conclusions were
      constant whether imaging was performed with or without MT. Scans in control
      studies did not demonstrate abnormal meningeal enhancement. High-contrast dose,
      MT, and acquisition of immediate postcontrast scans all resulted in statistically
      significant improvement. On masked film review, abnormal meningeal enhancement
      was noted in only 2 of 5 experimental dogs at a dose of 0.1 mmol/kg (regardless
      of the use of MT) compared with all animals at a dose of 0.3 mmol/kg. In 18 of 37
      dogs (paired scans with and without MT), when abnormal enhancement was noted, the
      use of MT improved the visualization of abnormal meningeal enhancement.
      CONCLUSIONS: In early brain meningitis, high-contrast dose (0.3 mmol/kg), MT, and
      scanning immediately after injection improve detection of abnormal meningeal
      enhancement, thus facilitating the diagnosis of meningitis. Of these factors,
      contrast dose is the most important.

PMID- 8557516
TI  - Theoretical considerations and in vitro results for the development of
      percutaneous transcatheter balloon embolectomy.
AB  - RATIONALE AND OBJECTIVES: To prove the feasibility of performing percutaneous
      transcatheter embolectomy using a funnel-shaped catheter tip and balloon
      embolectomy catheters. METHODS: A theoretical model is described to assess the
      influence of the diameter of an introductory device and coaxially introduced
      embolectomy catheter. A funnel-shaped catheter tip was attached to 7F, 8F, and 9F
      introductory sheaths. In vitro embolectomy of 5 g and 12 g thrombi was performed
      with 3F and 4F embolectomy catheters. RESULTS: The number of extractions required
      was significantly related to the ratio of the diameters of the sheaths and
      embolectomy catheter shafts. The combination of a 7F sheath with a 4F embolectomy
      catheter required the greatest number of extractions (8.4 +/- 1.7). The least
      number of extractions was needed for the combination of a 9F sheath with 4F and
      3F embolectomy catheters (1.6 +/- 0.7 and 1.8 +/- 0.4, respectively).
      CONCLUSIONS: Our results indicate that percutaneous embolectomy with balloon
      embolectomy catheters is feasible. However, further research is necessary before
      the final catheter design is chosen.

PMID- 8557517
TI  - Neuronal dysfunction in patients with closed head injury evaluated by in vivo 1H
      magnetic resonance spectroscopy.
AB  - RATIONALE AND OBJECTIVES: With the use of localized, water-suppressed in vivo 1H
      magnetic resonance spectroscopy (MRS), the proton metabolic alterations of white
      matter in patients with closed head injury (CHI) and healthy controls are
      evaluated, and metabolic alterations with Glasgow Outcome Scale (GOS) scores are
      compared. METHODS: Patients with CHI (n = 10) and healthy control subjects (n =
      10) underwent MRS examinations using a stimulated-echo acquisition mode pulse
      sequence that provided 2 x 2 x 2 cm3 volume of interest in the left
      frontoparietal white matter. Proton metabolite ratios relative to creatine were
      obtained using a Marquart algorithm. RESULTS: The specific feature in patients
      with CHI was significant decrease of N-acetylaspartate (NAA)/creatine ratio
      compared with normal controls. No clear correlation of other metabolite ratios
      such as choline/creatine and inositols creatine was established. The level of
      NAA/creatine ratio was significantly correlated with GOS. CONCLUSIONS: Results of
      this preliminary study suggest that the reduction of NAA/creatine ratio may
      indicate neuronal loss in patients with CHI. The NAA/creatine ratio may serve as
      a metabolic criterion to predict the GOS of patients with CHI. Thus, in vivo 1H
      MRS may be a useful modality in the clinical evaluation of patients with CHI
      based on the proton metabolite concentrations of cerebral white matter.

PMID- 8557518
TI  - Effect of phosphodiesterase inhibition on IL-4 and IL-5 production of the murine
      TH2-type T cell clone D10.G4.1.
AB  - The effect of various phosphodiesterase (PDE) inhibitors on anti-CD3 induced
      interleukin-(IL)-4 and IL-5 production of the murine T helper cell clone of type
      2 phenotype D10.G4.1 (D10) has been investigated in vitro. D10 cells were
      incubated in the presence of drugs and anti-CD3 mAb for 16 h before measurement
      of cytokines in the cell supernatants by ELISA. Whereas all PDE inhibitors tested
      exerted minimal effects on anti-CD3 induced IL-4 production, a marked increase in
      IL-5 production by the non-selective PDE inhibitors IBMX, theophylline and
      enprofylline was observed. The action of these non-selective PDE inhibitors was
      mimicked by the PDE IV-selective inhibitor rolipram and in part by the PDE III
      selective inhibitors motapizone and milrinone, whereas the PDE V-selective
      inhibitor zaprinast was inactive. Rolipram and motapizone enhanced IL-5
      production in a synergistic fashion. In support of the functional importance of
      PDE III and IV for IL-5 synthesis in intact murine D10 cells, we have found PDE
      III and IV to be the predominant isoenzyme activities in corresponding cell
      lysates. The stimulatory effect of rolipram on IL-5 production was almost totally
      reversed by the protein kinase A inhibitor KT-5720. In addition, the membrane
      permeable cAMP analogue 8-bromo-cAMP mimicked the stimulatory effect of PDE
      inhibitors on IL-5 production while leaving IL-4 levels unaffected. Both results
      support the view that the action of the PDE inhibitors on murine D10 cells is
      mediated via an elevation of intracellular cAMP.

PMID- 8557519
TI  - Interleukin-2 receptor (CD25) upregulation on human T-lymphocytes: sensitivity to
      immunosuppressants is defined by the mode of T-lymphocyte activation.
AB  - We investigated the transcription and expression of the interleukin-2 receptor
      (IL-2R, CD25) in human T-lymphocytes after different modes of T-lymphocyte
      stimulation in the presence of the immunosuppressants cyclosporin (CsA) and
      tacrolimus (FK506) as well as the structurally related macrolide rapamycin. We
      demonstrate that CsA and FK506 inhibited IL-2R (CD25) gene transcription and
      protein expression after stimulation by anti-CD3 or ionomycin, but not by phorbol
      ester or IL-2. Rapamycin, which does not affect IL-2 transcription, surprisingly
      inhibited IL-2R upregulation after anti-CD3- or ionomycin-induced stimulation,
      but not by phorbol ester or IL-2. Interestingly, the protein synthesis inhibitor
      anisomycin inhibited anti-CD3- or ionomycin-, but not phorbol ester- and IL-2
      induced CD25 gene transcription indicating the dependence on de novo protein
      synthesis of the former pathways. These data suggest that the pharmacological
      effect of the imunosuppressants tested on IL-2R gene expression may be predicted
      by the requirement of protein synthesis of a given activation pathway.

PMID- 8557520
TI  - Dissociation between the mitogenic effect and antitumor activity of seed extract
      from Aeginetia indica L.
AB  - The extract from seeds of Aeginetia indica L. (AIL), a parasitic plant, induces
      potent antitumor immunity against Meth A fibrosarcomas in BALB/c mice. AIL also
      possesses a thymocyte co-stimulatory effect in vitro with suboptimal dose of Con
      A, a B cell mitogenic effect, and stimulates AIL-primed CD4+ T cells to produce
      Th1-type cytokines. In this study, we investigated the relationship between
      mitogenicity and antitumor activity with AIL. When AIL was analyzed by SDS-PAGE,
      there was strong and diffuse staining in the region between 14 kDa and the bottom
      of polyacrylamide gel and it was unaffected when AIL was digested with proteinase
      K (PK) before SDS-PAGE. Some bands with different molecular mass were also found
      in silver-stained gel and they disappeared completely by incubating AIL with PK
      before SDS-PAGE. The in vitro thymocyte co-stimulatory and B cell mitogenic
      effects were not influenced by digesting AIL with PK but were completely
      suppressed by the oxidation of AIL with sodium periodate before culture. In
      contrast, the in vivo antitumor activity was completely abolished by PK, but it
      was not affected by periodate oxidation. We generated mAbs specific for AIL and
      investigated the influence on the antitumor activity of AIL in vivo. Around 60
      80% of tumor-bearing mice failed to recover from a challenge tumor when they were
      treated with supernatants isolated from mAb-induced precipitation reactions.
      Immunoblotting (Western blotting) revealed that all the mAbs reacted exclusively
      with a 50-60 kDa protein and that this reactivity was not influenced after
      oxidizing the blots with sodium periodate. We demonstrated that AIL contains
      polysaccharides and proteins. The polysaccharides induced B cell mitogenic and
      thymocyte co-stimulatory effects in vitro, while the proteins, especially a 50-60
      kDa protein containing non-carbohydrate epitopes recognized by the mAbs, mediated
      antitumor activity in vivo.

PMID- 8557521
TI  - Enhancement of phagocytosis in mouse macrophages by pituitary adenylate cyclase
      activating polypeptide (PACAP) and related peptides.
AB  - The effects of pituitary adenylate cyclase activating polypeptide (PACAP) and
      related peptides on phagocytosis of fluorescent latex beads by mouse peritoneal
      macrophages were examined using flow cytometry (FCM). PACAP38, PACAP27 and
      vasoactive intestinal peptide (VIP) enhanced phagocytosis in a dose-dependent
      manner. Relative potencies of related peptides at a concentration of 10(-6) M
      were PACAP38 > PACAP27 > VIP > secretin > glucagon > (peptide with NH2-terminal
      histidine and COOH-terminal methionine amide, in short PHM). PACAP(6-38) was as
      effective as PACAP38. PACAP(6-27) enhanced phagocytosis more effectively than did
      PACAP27. PACAP(28-38) slightly enhanced phagocytosis. The present result suggest
      that PACAP38 is one of the mediators that the nervous system uses to modulate the
      immune system.

PMID- 8557522
TI  - The effect of chronic treatment with imipramine on the immunoreactivity of
      animals subjected to a chronic mild stress model of depression.
AB  - A depression-like state was induced in Wistar rats by chronic (3-week) exposure
      to very mild, unpredictable stress, which led to diminished food consumption and
      diminished preference for sweet drinks (anhedonia). Anhedonia was then abolished
      by 5 weeks of daily administration of imipramine to the continually stressed
      animals. One day after the last drug injection and stressful event, a
      statistically significant decrease in the proliferative activity of splenocytes
      to Con A stimulation in vitro was observed in those animals. Eight weeks of
      stress (without antidepressant therapy) affected likewise, but in a less potent
      and non-significant manner, the activity of splenocytes. Administration of
      imipramine alone for a period of 5 weeks did not modify the activity of these
      cells.

PMID- 8557523
TI  - Modulatory effect of plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) on
      macrophage functions in BALB/c mice. I. Potentiation of macrophage bactericidal
      activity.
AB  - The modulatory ability of plumbagin, a natural product from Plumbago zeylanica,
      was studied on peritoneal macrophages of BALB/c mice. The macrophage functions
      evaluated were bactericidal activity, hydrogen peroxide and superoxide anion
      release. The bactericidal capacity of in vivo plumbagin-treated mouse macrophages
      was estimated against Staphylococcus aureus. In low doses plumbagin exerted a
      constant increase in bactericidal activity throughout the study period whereas
      with a high dose a higher response was observed up to six weeks. But in the next
      two weeks a considerable decline in the bactericidal activity was noticed
      compared to low dose. Plumbagin was also seen to exert a similar response on
      oxygen radical release by macrophages in vivo showing a clear correlation between
      oxygen radical release and the bactericidal activity. The data indicate that
      plumbagin augments the macrophage bactericidal activity by potentiating the
      oxyradical release at low concentration whereas at the higher concentration it
      has inhibitory activity.

PMID- 8557524
TI  - Pharmacodynamics of prophylactic antirejection therapy with an anti interleukin-2
      receptor monoclonal antibody (BT563) after heart and kidney transplantation.
AB  - A mouse monoclonal antibody (BT563) directed to the alpha-chain of the IL-2
      receptor was administrated immediately after transplantation in a dose of 10
      mg/day prophylactically to 30 heart transplant recipients (HTx) and 40 renal
      transplant recipients (RTx) to induce immunosuppression. Plasma levels increased
      to a plateau level of 5300 ng/ml in HTx and 5900 ng/ml in RTx. BT563 plasma
      disappearance curves gives a mean T1/2 of respectively 39 h (range 14-112 h) and
      42 h (range 8-122 h) for HTx and RTx respectively. The CD25 marker (IL-2R) on the
      peripheral blood lymphocytes disappeared within hours after the first gift and
      returned to normal within 0-20 days after the last gift. In HTx more often CD25+
      cells were found in the presence of BT563 and more rejections occurred shortly
      after discontinuation of BT563 compared to the RTx group. Rejectors and non
      rejectors within the HTX group did not differ with respect to the period of
      depletion of CD25 positive cells in the peripheral blood. In 56% of the patients
      a substantial IgM antibody response was detected. This response was similar for
      HTx and RTx and not related to rejection. The frequency of IgG responses was low
      in both HTx (13%) and RTx (21%) patients and the IgG response was not related
      with graft rejection or with antirejection treatment. Peripheral monitoring
      showed that mAb plasma levels, antimurine antibody responses and number of CD25
      positive cells were not related with the clinical results. The mAb BT563 proved
      to be safe with respect to the generation of antimurine antibodies and, when
      given in combination with CsA, is a therapy with a potential for high efficacy.

PMID- 8557525
TI  - Effects of isoniazid treatment on human lymphocyte proliferative response,
      lymphocyte subsets and natural killer cell activity.
AB  - The effect of isoniazid on proliferative response, natural killer (NK) cell
      activity and lymphocyte subset distribution of blood mononuclear cells (BMNC) was
      investigated. To evaluate the effect of treatment with isoniazid in pharmacologic
      concentrations, twenty healthy HIV-seronegative volunteers were randomized into
      two groups: one group received isoniazid tablets plus pyridoxin tablets once a
      day for 30 days, the other group received pyridoxin only. Blood samples were
      collected on day 0 and day 30. Inhibition of the PHA-induced proliferative
      response was demonstrated in lymphocyte cultures from isoniazid-treated
      volunteers (p < 0.001). However, no effect was seen on the IL-2- or antigen (PPD)
      induced proliferative response or the NK cell activity of isolated BMNC.
      Inhibition of the PHA-induced proliferative response could not be related to
      changes in the distribution of CD3+, CD4+, CD8+, CD14, or CD19+ lymphocyte
      subsets. The effects, in vitro, were investigated by addition of isoniazid to
      cultures of BMNC isolated from either HIV-seroposive or HIV-seronegative donors
      who did not receive any treatment. We found that isoniazid did not influence the
      mitogen- or antigen-stimulated proliferative response or the NK cell activity.

PMID- 8557526
TI  - Survey of Hawaii physicians' attitudes on health care reform.
AB  - Hawaii is more important in health care that its size suggests. It is the first
      state in the U.S. to have mandated employer-funded health insurance for all
      workers, and to realize near universal coverage for residents. Because of that,
      the U.S. can benefit from the experience of those who deliver health services to
      the people of Hawaii. To determine some of the problems in the current system and
      what physicians see as solutions, a study of the attitudes and experiences of
      local physicians was conducted.

PMID- 8557527
TI  - After five decades, can health care costs be controlled without sacrificing
      quality?

PMID- 8557528
TI  - Polymerase chain reaction in situ: an appraisal of an emerging technique.
AB  - Polymerase chain reaction (PCR) in situ is a new technique which promises to
      enhance considerably our ability to detect a few copies of target nucleic acid
      sequences in fixed tissues and cells. It has an enormous potential for
      application in diagnostic histopathology of viral diseases and in the study of
      gene expression. PCR in situ is, however, technically difficult, and
      amplification of the target DNA is only 30-300 fold. In this article we present
      an overview of PCR in situ techniques used to amplify both DNA and RNA targets
      (RT-PCR in situ). We also identify problems which can reduce the efficiency of
      the technique or which can give rise to false-positive results. They include (1)
      the inhibitory effects of cross-linking of histones to DNA or PCR amplification,
      (2) abstraction of PCR reagents by tissue-bonding agents which are used to coat
      glass slides, (3) poor denaturation of target DNA and subsequent DNA renaturation
      due to extensive cross-linking of histones to DNA, or because of incorrect
      temperature regulation of thermal cyclers, (4) false-positive results which arise
      from end-labelling of DNA strand breaks by Taq polymerase, and (5) diffusion of
      PCR products into and out of cells leading to false-positive results. We present
      some of the approaches that have been used to overcome some of these difficulties
      and suggest new avenues for investigation to improve this technique further.

PMID- 8557530
TI  - Histochemical study of glycoconjugates in the epididymis of the hamster
      (Mesocricetus auratus).
AB  - The glycoconjugates of hamster epididymis were investigated with conventional and
      lectin histochemistry. A zone of the caput epididymis, with particular
      histochemical characteristics, has been differentiated. beta-Elimination in
      combination with lectins was used to establish the presence and distribution of N
      and O-linked glycoconjugates. The epithelium, spermatozoa and the intertubular
      matrix were rich in glycoconjugates. The Golgi apparatus and stereocilia of the
      principal cells were intensely positive with HPA, PNA and SBA lectins. beta
      Elimination indicated that these cells contained abundant O-linked
      glycoconjugates. Apical and clear cells presented a common lectin affinity; their
      reactivities towards WGA and UEA-I were very positive. These cells probably
      contain abundant N-glycoconjugates. The spermatozoa were stained by periodic acid
      Schiff (PAS) and by all the lectins (especially in the acrosome), except by those
      with an affinity for alpha-L-fucosyl residues; the most intense reaction was
      found with HPA, WGA, PNA and SBA. Changes in the sperm lectin binding along the
      ductus were observed: sperm flagellum abruptly acquired WGA and PNA labelling
      from the posterior caput, and HPA reactivity was negative only in the zone
      between the caput and the corpus.

PMID- 8557529
TI  - PCR in situ: aspects which reduce amplification and generate false-positive
      results.
AB  - PCR in situ promises the ability to amplify and detect very low levels of target
      nucleic acid in tissues. Despite considerable effort, the technique is still
      technically difficult and has not yet proved to be reliable or reproducible. We
      have now identified a number of factors which can contribute to the poor
      amplification of the target DNA and to the generation of false-positive signals.
      These factors include the effects of fixation, reagent abstraction, DNA
      degradation, DNA end-labelling and product diffusion. We present evidence to show
      that formaldehyde fixation cross-links histones to DNA and thus restricts the
      subsequent amplification of target sequences by PCR. End-labelling of DNA occurs
      when direct incorporation is used to detect amplified products and this gives
      rise to false-positive signals. Amplified products can also diffuse out of cells
      and into neighbouring cells which do not contain target sequences. They can
      undergo re-amplification within these cells giving rise to false-positive
      signals. We believe considerable caution should be exercised in the
      interpretation of results generated using PCR in situ.

PMID- 8557531
TI  - A cytophotometric and electron-microscopical study on catalase activity in serial
      cryostat sections of rat liver.
AB  - The validity of the histochemical procedure for demonstrating catalase activity
      in cryostat sections of rat liver at the light- and electron-microscopical level
      was studied cytophotometrically. Incubations in the presence of 5 mM
      diaminobenzidine, 44 mM hydrogen peroxide and 2% polyvinyl alcohol performed on
      fixed cryostat sections resulted in the highest amounts of final reaction product
      precipitated in a fine granular form which was specific for catalase activity.
      Serial sections processed for electron microscopy indicated that the osmiophilic
      final reaction product was exclusively localized in the matrix and core of
      peroxisomes. The relationship between incubation time and the amounts of final
      reaction product generated by catalase activity as measured at 460 nm in mid
      zonal areas of liver lobules showed non-linearity for the test-minus-control
      reaction because first-order inactivation of the enzyme occurred during
      incubation. Linearity of the test-minus-control reaction and section thickness
      was observed up to 8 microns. Catalase in rat liver showed a Km value of 2.0 mM
      for its substrate hydrogen peroxide when the diaminobenzidine concentration was 5
      mM. It is concluded that the procedure for demonstrating catalase activity in
      serial cryostat sections of rat liver at the light- and electron-microscopical
      level is specific and can be applied to quantitative purposes. This approach may
      be useful in pathology, when only small biopsies are available, when the tissue
      is heterogeneous, and when other histochemical markers also need to be studied in
      the same material.

PMID- 8557532
TI  - Expression of the CD15 antigen (Lewis x) in breast cancer.
AB  - The expression of the cell adhesion molecule CD15 (also known as Lewis x) by
      breast cancers and by adjacent normal and benign breast epithelium was
      investigated in a series of 98 tumours. Immunohistochemistry was performed on
      paraffin sections using the anti-CD15 monoclonal mouse IgM antibody Dako-M1. Some
      35% of cancers expressed CD15, as did 45% of normal and 60% of hyperplasia. No
      association was observed between cancer cell staining, or any epithelial staining
      (cancer, benign and normal), and tumour size, histological grade, nodal status,
      age at diagnosis or the frequency of 'events' (recurrence or death). Chi-squared
      tests in each case were non-significant. The pattern of CD15 expression by breast
      cancer was frequently associated with the leading edge of invading tumour or with
      the outer edge of boli of carcinoma in situ, possibly suggesting a potential role
      in invasiveness, and with cancer cells trapped intravascularly, possibly
      suggesting a role in metastasis.

PMID- 8557533
TI  - Immunohistochemical distribution of S-100 protein and type IV collagen in human
      embryonic and fetal sympathetic neuroblasts.
AB  - The expression and distribution of S-100 protein and type IV collagen was studied
      immunohistochemically in sympathetic neuroblasts from the paravertebral region to
      the adrenal glands in human embryos and fetuses ranging from 7 to 12 weeks
      gestational age. From 7 weeks gestational age, S-100 protein was detected in
      round or oval cells mingling with sympathetic neuroblasts, and in spindle-shaped
      cells forming a continuous layer around them. The latter S-100 protein-positive
      cells were found in contact with the Schwann cells of nerve fibres entering the
      groups of sympathetic neuroblasts. Staining for type IV collagen showed that all
      groups of sympathetic neuroblasts were surrounded by a continuous basement
      membrane. By examining serial sections stained for type IV collagen and S-100
      protein, a continuous basement membrane was found along the distribution pattern
      of the peripheral S-100 protein-positive spindle cells. The morphology of these
      cells, and their relationships with Schwann cells and with the basement membrane
      of the sympathetic neuroblasts, indicated that they were Schwann-like cells
      probably capable of synthesizing a continuous basement membrane separating the
      neuroblasts from the adjacent tissues. In contrast, the round or oval S-100
      protein-positive cells, in contact with the sympathetic neuroblasts and not
      associated with nerve fibres, were considered as sustentacular or sustentacular
      precursor cells. At week 7 gestational age, the peri-adrenal sympathetic
      neuroblasts and their sustentacular and Schwann-like cells started to invade the
      adrenal glands and mingled with the adrenal cortical cells. These findings
      suggest the extra-adrenal origin of the sustentacular cells in embryonic and
      fetal adrenal glands.

PMID- 8557534
TI  - Histochemistry of sarcoplasmic reticulum Ca-ATPase using dysprosium as capturing
      reagent.
AB  - This report describes the development of a histochemical method for the
      demonstration of sarcoplasmic reticulum Ca-ATPase activity in cross-sections of
      skeletal muscle. The demonstration of sarcoplasmic reticulum Ca-ATPase activity
      is complicated by the fact that capturing reagents for phosphate inhibit the
      enzyme. We present a minimal model for heavy-metal-phosphate precipitation
      reactions which gives a theoretical description of the effect of enzyme
      inhibition on the rate of phosphate precipitation in the section. The model
      indicates that the choice of capturing reagent is crucial: whether or not ATPase
      activity can be demonstrated depends mainly on the inhibition constant and the
      solubility product of the phosphate salt of the capturing reagent (but also on a
      fairly large number of other factors). All lanthanides tested can be used to
      demonstrate sarcoplasmic reticulum Ca-ATPase activity, but dysprosium results in
      the highest staining intensity. This suggests that dysprosium inhibits
      sarcoplasmic reticulum Ca-ATPase to a lesser degree than the other lanthanides
      and/or the solubility product of its phosphate salt is smaller. As an example,
      the method is used to investigate the effect of thyroid hormone on sarcoplasmic
      reticulum Ca-ATPase activity in individual fibres of the rat soleus muscle.

PMID- 8557535
TI  - The mATPase histochemical profile of rat type IIX fibres: correlation with myosin
      heavy chain immunolabelling.
AB  - In the present study we report a novel histochemical method which, by sequential
      pre-incubations in alkaline and acidic media, selectively differentiates muscle
      fibres expressing myosin heavy chain IIX, on the basis of a specific profile for
      myofibrillar actomyosin ATPase (mATPase) activity. The enzyme reactions were
      tested for specificity by means of anti-myosin heavy chain monoclonal antibodies,
      which were characterized on Western blots of muscle homogenates. Enzyme
      histochemical reactions with the traditional pH buffers were compared to those of
      the new method and, in conjunction with the immunoreactions, used to confirm the
      relationship between MyHC expression and the distinct profiles for mATPase.
      Immunohistochemical reactions demonstrated that the new method only
      differentiates those fibres expressing myosin heavy chain IIX. The method
      revealed a continuum in which the intermediate staining intensities corresponded
      to hybrid fibres expressing myosin heavy chain IIX in combination with either the
      IIA or IIB forms. Quantitative histochemistry and immunohistochemistry (by image
      analysis), used to examine the relationship between staining intensities for
      mATPase and amounts of myosin heavy chain IIX expression, revealed that the new
      method discriminates well between hybrid fibres expressing variable amounts of
      the IIX isoform (r2 = 0.93).

PMID- 8557536
TI  - Effects of mood states, smoking and urinary catecholamine excretion on hemoglobin
      A1c in male Japanese workers.
AB  - To know the association between psychological strain and glycosylated hemoglobin
      (HbA1c) and to examine roles of smoking and catecholamine excretion as a possible
      mediator in the association, we measured mood states (Profile of Mood States,
      POMS), urinary catecholamines (adrenalin, noradrenaline and dopamine) from urine
      sample in early morning, HbA1c and fasting plasma glucose (FPG) of 63 male
      employees on a rest day. After excluding 12 subjects who had diabetes or impaired
      glucose tolerance or had missing response to the questionnaire, data from 51
      subjects were analyzed. The POMS anger-hostility score significantly and
      positively correlated with HbA1c (p < 0.05), while other scale scores did not (p
      > 0.05). Number of cigarettes smoked per day significantly and positively
      correlated with HbA1c (p < 0.05). Urinary excretion rate of any catecholamine did
      not significantly correlate with HbA1c (p > 0.05). Multiple linear regression
      analysis indicated that the anger-hostility score significantly correlated with
      HbA1c after controlling for number of cigarettes per day (p < 0.05). It is
      suggested that, among mood states, anger-hostility is associated with increased
      HbA1c. However, our study failed to find a mediating role of urinary
      catecholamines or smoking on the association between the mood and HbA1c.

PMID- 8557537
TI  - Dyspnea and exercise testing in workers exposed to silica.
AB  - In order to provide a better objective assessment of exertional dyspnea and
      functional impairment due to exposure to silica, 153 workers exposed to silica
      dust (workers) and 62 patients with silicosis (patients) were performed the
      medical questionnaires with special reference to exertional dyspnea and exercise
      testing on bicycle ergometer. Complaints of breathlessness were present in 77
      (50%) workers and 53 (85%) patients. The findings of exercise tests indicated
      that there were definite correlations between index of dyspnea (ID), or breathing
      reserve (BR) and complaint of breathlessness in both the workers and patients. ID
      increased and BR decreased with the increasing degree of breathlessness. We
      defined ID > 70% or BR < 25 I/min as abnormal criteria and checked the ratios of
      dyspnea quantified objectively. Thus, 30% of the workers and 56% of the patients
      in this study were verified to have slight or moderate breathlessness, which were
      considerably lower than that derived from questionnaire on dyspnea. OUr results
      suggest that objective physiological measures like exercise testing may be of
      value in evaluating dyspnea in workers exposed to silica.

PMID- 8557538
TI  - Effects of smoking on respiratory function and exercise performance in asbestos
      workers.
AB  - To determine the role of smoking in the development of pulmonary impairment in
      asbestos workers, 66 nonsmoking asbestos workers and 70 smoking asbestos workers
      were studied. Occupational and medical questionnaires, lung function and exercise
      test were conducted in all subjects. The frequencies of dyspnea and cough on
      questions were significantly higher in the smoking workers than those in
      nonsmoking workers. Similarly, FEV1, FEV1/FVC and DLco were significantly lower
      in the smoking workers. Exercise performance showed that the smoking workers had
      higher index of dyspnea and lower breathing reserve, Vo2 and Vo2 max than
      nonsmoking workers did. We concluded that cigarette smoking has marked effects on
      both of respiratory function and exercise performance in asbestos workers. Among
      them, smokers show more serious obstructive impairment in static lung function
      testing and more significant limitation during exercise. The history of cigarette
      smoking deserves close attention in the evaluation of pulmonary impairment from
      asbestos exposure.

PMID- 8557539
TI  - Assessment of interlaboratory performance on the measurement of blood lead levels
      in Taiwanese adults.
AB  - The purpose of this proficiency study was to assess the accuracy and consistency
      of blood lead level (BLLs) measurements in a study of Taiwanese adults. Three
      methods, including a certified blood accuracy test, an interlaboratory precision
      test and an intertime repeated measurement test, were applied to the six
      participating laboratories. Accuracy tests showed that most of the blood lead
      measurements were within the acceptable criteria proposed by United States Center
      for Disease Control and Prevention (U.S. CDC). However, an average of 11%
      underestimation was found at BLLs below 15 micrograms/dl. Coefficients of
      variation (CVs) were high in the first 3 months. After technical improvements,
      the CVs were reduced to acceptable limits of around 15% at low target lead values
      and 7% at high lead values. Interlaboratory variations of measurements in blood
      from ten normal healthy donors showed that the standard deviations were less than
      2 micrograms/dl, which is within the acceptable criteria of +/- 4 micrograms/dl,
      in 8 out of 10 samples. Repeated measurements of BLLs in 54 blood samples over
      two months showed that most of the differences were within the acceptable range
      with a few exceptions. The mean BLLs measured in the baseline (pre-test) and two
      months later (post-test) were nearly identical. This proficiency test provides
      comparable and reliable results of BLL estimations in this multilaboratory study.
      However, the accuracy and consistency at low BLLs need to be improved.

PMID- 8557540
TI  - Accidents in the aluminium smelting industry.
AB  - Analysis of the accident records of an aluminium smelting industry, covering
      about 2,100 employees, over a period of three years, showed a total of 465
      accidents of male employees. Out of these, 5 were fatal, 40.86% were from
      contacts with extreme temperatures, causing burn injury to 42.58%. Hot materials
      were the agents causing 44.52% of the burn injuries. Molten aluminium constituted
      43.96% amongst hot materials. Injury to lower limbs constituted 38.71% and that
      to upper limbs 36.99%. The accidents occurring to the employees, in the age group
      of 26-33 years, amounted to 61.72% of the total accidents. The average number of
      man-days lost per year was 11,153. Average frequency rate of accidents was 30.75
      accidents per million man-hours worked. Severity rate of accidents was 2.196 per
      million man-hours worked. Incident rate per thousand employees was 73.81. Average
      number of days lost per accidents was 71.95 days and average duration of man
      hours between accidents was 32,516. Mean age of the employees, who met with the
      accidents were 29.53 years. Share of accidents in the second half of each shift
      was always more than that in the first half, and this average was 66.66%.

PMID- 8557541
TI  - Elevation of cystathionine gamma-lyase activity in the serum of rats treated with
      a single dose of carbon tetrachloride.
AB  - Cystathionine gamma-lyase activity in the sera of rats subjected to experimental
      hepatotoxicity after intraperitoneal administration of carbon tetrachloride
      (CCl4) was measured and compared with activities of aspartate aminotransferase
      (GOT) and alanine aminotransferase (GPT), which have been clinically used for
      detecting liver damage. In the experimental subjects, serum levels of
      cystathionine gamma-lyase showed a similar behavior to GOT and GPT, increasing
      markedly with respect to the controls after administration of CCl4 and reaching a
      maximum at 24 hours. No such cystathionine gamma-lyase activity was detected
      immunochemically in the control subjects. These data suggest that measurement of
      serum cystathionine gamma-lyase activity could be used as a sensitive and
      specific marker of hepatic cytolysis.

PMID- 8557542
TI  - A small-volume constant-flow air sampling device for thermal desorption GC
      analysis.
AB  - A glass syringe with disposable membrane filters was tested as a constant-flow
      air sampling device. The principle of this sampling device is straightforward:
      when the syringe is inverted vertically, the syringe plunger falls at a constant
      speed if an appropriate flow restrictor is connected at the syringe inlet. In
      case of a 100 ml syringe with two Teflon membrane filters of 0.50 microns in pore
      size and 3 mm in diameter, the flow rate was 3 ml/min. The flow rate was constant
      for a 15-minute sampling period when two to eight filters were used as a flow
      restrictor. A sample volume of less than 50 ml is sufficient for the
      determination of organic solvent vapor at the ppm level, when gas chromatography
      with thermal desorption method is employed. Therefore, this sampling device is
      useful for determining the time-weighted average concentrations of organic
      solvent vapor in a working environment.

PMID- 8557543
TI  - JAOA new members.

PMID- 8557544
TI  - Recount of prostaglandin E1 therapy in a patient with Raynaud's phenomenon.

PMID- 8557545
TI  - Preventive medicine indoctrination must begin at undergraduate level.

PMID- 8557546
TI  - Synergism strengthens osteopathic medical education programs.

PMID- 8557547
TI  - Occurrence and impact of suspected delirium in hospitalized elderly patients.
AB  - The records of 95 consecutive people older than 65 years and admitted to a
      community hospital were retrospectively reviewed to determine the prevalence of
      undiagnosed delirium in hospitalized elderly patients. Chart review focused on
      identification of patients with documented diagnosed delirium according to
      Diagnostic and Statistical Manual of Mental Disorders, third edition, revised
      (DSM-III-R) criteria and patients with unrecognized delirium. Unrecognized
      delirium was considered present when information contained in a patient's chart
      met some or all criteria for delirium as described in DSM-III-R, but the
      physician's progress notes failed to indicate delirium as a diagnosed clinical
      entity. The prevalence of diagnosed delirium was 2%. Thirty-six percent of the
      patients were suspected of having unrecognized delirium. The mean length of
      hospital stay and the rate of mortality were significantly higher for patients
      with suspected delirium than for non-delirious patients. The findings of this
      study suggest that unrecognized delirium in the hospitalized elderly may occur
      frequently and is associated with an increased length of hospital stay and
      increased mortality.

PMID- 8557548
TI  - Sickle cell disease: the clinical manifestations.
AB  - In the United States, sickle cell disease primarily affects people of African
      descent, and the multisystemic complications caused by the resultant vaso
      occlusive state create a multitude of diagnostic considerations. In the
      musculoskeletal system, likelihood is high for avascular necrosis of the femoral
      humeral head, as a consequence of skeletal infarcts, and also for leg ulceration
      and osteomyelitis; in the eyes, the incidence of proliferative retinopathy is
      high; in the urinary tract, dehydration is common, and causes for renal failure
      are many; in the pulmonary system, pneumonia is of prime concern, as are sickle
      cell chest syndrome (from occlusion within the microvasculature of the lung) and
      the deadly sickle cell chronic lung disease, for which pulmonary function tests
      are important in early asymptomatic stages. Cholelithiasis occurs in 40% of young
      adult patients with sickle cell disease and can be confused with sickle cell
      hepatopathy, and rheumatologic and immunologic diseases can occur concomitantly
      with sickle cell disease, with similar symptoms. The chance for stroke in
      patients with sickle cell disease is 25%, and early recurrence is common,
      although the pathogenesis has been more clearly elucidated through computed
      tomography and magnetic resonance imaging. Infection with Streptococcus
      pneumoniae has high mortality because of the asplenia associated with sickle cell
      disease.

PMID- 8557549
TI  - Residents' performance before and after night call as evaluated by an indicator
      of creative thought.
AB  - The effects of sleep deprivation on medical personnel have received much
      attention. This study evaluates the effects of sleep loss on divergent-thinking
      (creative or innovative) processes as measured by the Torrance Test of Creative
      Thinking (TTCT). Anesthesia residents who had approximately 30 minutes sleep
      while being on-call were evaluated. These physicians had similar caffeine and
      nicotine consumption before and after the test. The results reported here
      demonstrate that postcall residents had TTCT scores that were appreciably below
      those scores of rested residents. Postcall verbal fluency was less among the on
      call group than among the rested group (94.0 +/- 9.7 vs 101.8 +/- 9.8) as was
      figural originality (89.9 +/- 22.1 vs 113.3 +/- 20.3). These study results
      suggest that sleep deprivation affects divergent, or creative, thinking.
      Divergent-thinking processes are usually innovative and are used during complex
      problem-solving tasks. Further studies are needed on the effects of sleep
      deprivation. This information can then be used to help improve residents' working
      conditions and patient care.

PMID- 8557550
TI  - Female enrollment in colleges of osteopathic medicine: five years and five
      percentage points behind.
AB  - An estimated one fifth of graduates of the colleges of osteopathic medicine
      (COMs) before 1910 were women. However, the proportion of women declined after
      1900, so that by 1969, less than 3% of osteopathic medical students were women.
      Dramatic gains have been made in the past 25 years: for the 1993-1994 academic
      year, women made up 35% of all osteopathic medical students. Although these gains
      seem impressive, allopathic medical school enrollment comprised 40% women during
      the same academic year (5 percentage points higher than in osteopathic medical
      schools). Allopathic medical schools have had significantly more women enrolled
      every year between academic years 1969-1970 and 1993-1994. In academic year 1988
      1989, allopathic medical schools already had an enrollment that consisted of 35%
      female students, a percentage that COMs would first reach 5 years later. Based on
      these findings, enrollment of women in COMs is 5 years and 5 percentage points
      behind that of allopathic medical schools.

PMID- 8557551
TI  - Adult Arnold-Chiari malformation: a postpartum case presentation.
AB  - Adult Arnold-Chiari malformation, also known as Chiari malformation type I,
      typically occurs in women during early adulthood and can be a cause of
      unexplained headaches, as well as associated syringomyelocele. In this unique
      case report, a 32-year-old, postpartum woman with posturally induced headache
      from Chiari malformation type I had symptoms occur for the first time during
      pregnancy. Magnetic resonance imaging of the brain confirmed the diagnosis and is
      the neuroimaging study of choice in such cases. Neurosurgical decompression, when
      performed early, is highly successful in symptomatic individuals.

PMID- 8557552
TI  - Massive tissue necrosis after hydroxyzine injection.
AB  - A 47-year-old man hospitalized for disk surgery received a preoperative injection
      of hydroxyzine hydrochloride in the upper outer quadrant of the gluteal region.
      The immediate pain decreased after 3 days but later became incapacitating.
      Substantial tissue necrosis in the region of the injection was confirmed 4 weeks
      after the injection, and 100 g of necrotic tissue was excised, leaving the
      patient with lost muscle mass and a definite limp 2 years later. During the
      injection of hydroxyzine, the needle penetrated through the gluteal muscle and
      entered the gluteal artery, causing thrombosis of the artery and necrosis of the
      gluteus maximus muscle. This case and other reported cases indicate that the use
      of intramuscular hydroxyzine is contraindicated.

PMID- 8557553
TI  - Transitional cell carcinoma of the distal portion of ureter protruding into the
      sigmoid conduit six years after cystoprostatectomy.
AB  - Bladder tumors develop after the diagnosis of upper urinary tract carcinoma in
      approximately 20% of cases, whereas the incidence of upper urinary tract tumor
      after the diagnosis of bladder cancer is low, approximately 2%. In a 64-year-old
      man who had undergone cystoprostatectomy treatment of bladder carcinoma 6 years
      previously, with the sigmoid conduit used for supravesicle diversion, a
      transitional cell carcinoma that developed in the conduit was not revealed with
      intravenous pyelography at regular follow-up intervals. The patient had only
      hematuria. After an obstructed left kidney, left ureteral stricture, and a
      filling defect in the conduit were observed radiologically and biopsy revealed a
      transitional cell carcinoma at the ureterosigmoid junction, the patient underwent
      left nephroureterectomy, partial resection of a third of the sigmoid conduit, and
      right ureteral reimplantation. The occurrence of upper urinary tract carcinoma
      after treatment of bladder cancer should be considered even in light of
      intravenous pyelography that shows no abnormality; and when such carcinomas occur
      in this situation, disease involving the conduit should be ruled out.

PMID- 8557554
TI  - Adding life to the elder years.

PMID- 8557555
TI  - Functional abilities of elderly survivors of intensive care.
AB  - In a prospective, randomized study undertaken to determine if age, length of
      hospital stay, or severity of illness are predictors of future functional status
      after intensive care unit (ICU) admission, 45 patients were evaluated. Pre-ICU
      functional status was determined by using Activities of Daily Living (ADL),
      Instrumental Activities of Daily Living (IADL), Geriatric Depression Scale (GDS),
      and Mini-Mental State (MMS) examinations. Severity of illness was assessed by
      using the Acute Physiology Assessment and Chronic Health Evaluation (APACHE-II)
      system. There were no significant differences in age or APACHE-II score at 6
      month followup. However, in those patients who had decreased ADL and IADL scores,
      ICU and total hospital length of stay were two and three times longer,
      respectively. Functional status at 6-months was unrelated to age or severity of
      illness, but correlated with the length of ICU and total hospital stay. Advanced
      age and severity of illness should not be used to predict future functional
      ability.

PMID- 8557556
TI  - A trek to the top: a review of acute mountain sickness.
AB  - Acute mountain sickness (AMS) affects, to varying degrees, all travelers to high
      altitudes (elevations greater than 5280 feet). In a small percentage of patients,
      AMS can lead to high-altitude pulmonary edema (HAPE) or high-altitude cerebral
      edema (HACE). Symptoms of AMS range from a combination of headache, insomnia,
      anorexia, nausea, and dizziness, to more serious manifestations, such as
      vomiting, dyspnea, muscle weakness, oliguria, peripheral edema, and retinal
      hemorrhage. Although the primary cause of these symptoms is related to the
      reduced oxygen content and humidity of the ambient air at high altitudes, the
      physiologic pathway relating hypoxemia to AMS and its sequelae remains unclear.
      Tips on self-diagnosis and symptom recognition are critical elements to be
      included in educating patients who are contemplating a trip to high altitudes.
      Preventive strategies include allowing 2 days of acclimatization before engaging
      in strenuous exercise at high altitudes, avoiding alcohol, and increasing fluid
      intake. Conditioning exercise for patients older than 35 years is also
      recommended before departure. A high-carbohydrate, low-fat, low-salt diet can
      also aid in preventing the onset of AMS. Acetazolamide (125 mg two or three times
      daily, or once at bedtime) has also been shown to reduce susceptibility to AMS
      and the incidence of HAPE and HACE. Although effective in treating cerebral
      symptoms of AMS, dexamethasone is not routinely recommended as a prophylactic
      agent for AMS.

PMID- 8557557
TI  - Reexamination of the paradigm of HIV risk reduction in adolescents.
AB  - Infection with the human immunodeficiency virus (HIV) in the adolescent/young
      adult population of the United States is a serious, growing problem. The current
      HIV risk-reduction strategies for adolescents have been less than effective in
      stemming the tide of infection. This ineffectiveness can be linked to failure of
      making developmentally appropriate risk-reduction informational material and
      reliance on condom-based interventions, which have an unacceptably high failure
      rate. A critical analysis of current models of HIV-risk reduction should be
      undertaken to create more developmentally appropriate and effective methods.

PMID- 8557558
TI  - Enzymatic synthesis of hydrophobic penicillins.
AB  - Our knowledge of the enzymes and genes involved in the biosynthesis of beta
      lactam antibiotics has increased notably in the last decade. The purification to
      homogeneity of some of these proteins as well as their biochemical
      characterization has allowed some of them to be used for synthesizing many
      different penicillins and cephalosporin-like products in vitro. In this report we
      describe the most important advances in this field, placing special emphasis on
      the enzymatic synthesis of hydrophobic penicillins. The use of purified acyl-CoA:
      6-aminopenicillanic acid (6-APA) acyltransferase (AT) from Penicillium
      chrysogenum and several acyl-CoA ligases obtained from different microbial
      origins has led to the reproduction "in vitro" of the last step involved in in
      penicillin biosynthesis. By coupling these enzymatic systems (AT and acyl-CoA
      ligases) an impressive number of beta-lactam antibiotics has been obtained. Thus,
      most of the known natural penicillins, many of the semisynthetic variants and
      others, which until now can only be obtained chemically, have been synthesized
      enzymatically from their natural precursors. Furthermore, the use of heterologous
      proteins in coupled systems has opened a new and exciting field in beta-lactam
      antibiotic research, lending new perspectives to the traditional methodology
      followed by antibiotic fermentation industries.

PMID- 8557559
TI  - RES-701-2, -3 and -4, novel and selective endothelin type B receptor antagonists
      produced by Streptomyces sp. I. Taxonomy of producing strains, fermentation,
      isolation, and biochemical properties.
AB  - RES-701-2, -3 and -4, novel cyclic peptide endothelin antagonists, were isolated
      from the culture broths of Streptomyces sp. RE-701 and RE-896, RES-701s
      selectively inhibited the ET-1 binding to endothelin type B receptor (ETB
      receptor) with IC50 values ranging from 5 to 20 nM. Taxonomy of the producing
      strains, fermentation, isolation and biochemical properties of RES-701s are
      described.

PMID- 8557560
TI  - Monamidocin, a novel fibrinogen receptor antagonist. I. Production isolation,
      characterization and structural elucidation.
AB  - Monamidocin, a novel fibrinogen receptor antagonist, has been isolated from the
      culture broth of Streptomyces sp. NR 0637 BY carbon adsorption, n-BuOH
      extraction, SP-Toyopearl, silica gel 60 silanised and Sephadex LH-20 column
      chromatographies and preparative HPLC. The molecular formula of monamidocin has
      been determined to be C15H22N4O4 from HRFAB-MS and 13C NMR spectral data. The
      structure of monamidocin has been determined to be N-[(S)-5-guanidino-2
      hydroxypentanoyl]-L-phenylalanine by 2D NMR experiments.

PMID- 8557562
TI  - A new antiherpetic agent produced by Streptomyces sp. strain no. 758.
AB  - A new antiherpetic agent, AH-758, was isolated from the culture broth of
      Streptomyces sp. strain No. 758. The structure was determined by NMR special
      analyses to be a new antibiotic belonging to bafilomycin group containing (5-oxo
      2-pyrrolin-2-yl) methyl fumarate in its C-21.

PMID- 8557561
TI  - Monamidocin, a novel fibrinogen receptor antagonist. II. Biological activity and
      structure-activity relationships.
AB  - Monamidocin, a fibrinogen receptor binding inhibitor produced by Streptomyces sp.
      NR 0637, inhibits the binding of fibrinogen to its receptor with an IC50 of 0.21
      microM. It also inhibits ADP-collagen- and thrombin-induced aggregation of human
      platelet with IC50S of 46, 30, and 77 microM, respectively. To obtain more potent
      inhibitors, twenty analogs have been synthesized, among which N-[(R)-5-guanidino
      2-hydroxypentanoyl]-L-tyrosine is the most potent. It inhibits the binding of
      fibrinogen to its receptors with an IC50 of 0.022 microM and is about ten times
      more potent than monamidocin.

PMID- 8557563
TI  - Bacillomycin Lc, a new antibiotic of the iturin group: isolations, structures,
      and antifungal activities of the congeners.
AB  - Bacillomycin Lc, a new antifungal antibiotic of the iturin class, was isolated
      from a strain of Bacillus subtilis as a set of five congeners. The structure as
      determined by chemical and spectrometric analyses has been shown to differ from
      that of bacillomycin L by sequence changes from aspartate-1 to asparagine-1 and
      from glutamine-5 to glutamate-5. The five congeners differ from each other only
      in the structure of the aliphatic side chain of the constituent beta-amino acid.
      The hydrophobicity of the beta-amino acid affects the antifungal activity of the
      congener, as activity increased in the order of increased congener retention on a
      reversed-phase HPLC column.

PMID- 8557564
TI  - Trichorzins HA and MA, antibiotic peptides from Trichoderma harzianum. I.
      Fermentation, isolation and biological properties.
AB  - Trichorzins HA and MA, original 18-residue peptides, were isolated from two
      strains of the widespread soil fungus Trichoderma harzianum which have been shown
      to exhibit antibiotic activity against phytopathogenic fungi. These linear
      peptides belonging to the peptaibol class are biosynthesized as a complex of
      closely related analogues. Nine major pure peptides, six trichorzins HA and three
      trichorzins MA, were isolated by reversed-phase HPLC. The isolated peptides
      exhibited antibacterial activity against S. aureus and increased the membrane
      permeability of egg phosphatidylcholine/cholesterol (7/3) liposomes, as measured
      by monitoring leakage kinetics of a fluorescent probe. Structure-activity
      relationships were deduced from the antibiotic and membrane-modifying properties.

PMID- 8557565
TI  - Trichorzins HA and MA, antibiotic peptides from Trichoderma harzianum. II.
      Sequence determination.
AB  - A series of 18-residue antibiotic-antifungal peptides, trichorzins HA and MA,
      were isolated from Trichoderma harzianum strains exhibiting antagonistic
      properties against phytopathogenic fungi. The sequences of the nine major pure
      peptides isolated by HPLC were determined by positive ion FAB-MS data and two
      dimensional NMR measurements, including COSY, HOHAHA, ROESY and 1H-13C LRCOSY
      experiments.

PMID- 8557566
TI  - Chondramides A approximately D, new antifungal and cytostatic depsipeptides from
      Chondromyces crocatus (myxobacteria). Production, physico-chemical and biological
      properties.
AB  - Novel depsipeptides, named chondramides were produced at levels up to 4.3
      mg/liter by several myxobacteria of the genus Chondromyces. The compounds are
      structurally closely related to jaspamide/jasplakinolide from marine sponges of
      the genus Jaspis. Initially the chondramides were detected in acetone extracts of
      the biomass of Chondromyces crocatus, strain Cm c2. So far, four structural
      variants could be characterized, the chondramides A approximately D. They
      inhibited the growth of a few yeasts and showed high cytostatic activity against
      cultivated human and animal cells.

PMID- 8557567
TI  - PCR inhibition assay for DNA-targeted antibiotics.
AB  - DNA amplification by polymerase chain reaction (PCR) should be inhibited if the
      target for amplification region in the template DNA is nicked or cut. Based on
      this premise, we established a sensitive and differential assay using PCR to
      detect antibiotics that act on DNA. After template lambda DNA (10 pg) was
      incubated with antibiotics (10 approximately 20 ng) at 37 degrees C for 30
      minutes in a 5 microliters reaction volume, a PCR assay (10 microliters reaction
      volume; 25 approximately 30 cycles) was performed under the conditions we
      modified, resulting in amplification of a 500 bp fragment of lambda DNA which was
      monitored by agarose gel electrophoresis. Among the several antibiotics examined,
      the anthracyclines, bleomycin, D-cycloserine and mitomycin C clearly inhibited
      the PCR amplification reaction, whereas actinomycin D and ofloxacin did not.
      Preincubation of template DNA in the presence of Fe++ was necessary for bleomycin
      and cycloserine to exhibit marked inhibition of PCR. Mitomycin C exhibited the
      inhibition in the presence of DTT and Cu+. By contrast, non-DNA-acting
      antibiotics (200 ng) such as aminoglycosides, beta-lactams, and macrolides showed
      no inhibition. The PCR-amplified fragment from lambda DNA was not degraded by
      incubation with the antibiotics (20 ng) that inhibited PCR. Furthermore,
      ethylacetate extracts of the cultured broths of actinomycetes proved to be
      suitable as samples for this PCR inhibition assay.

PMID- 8557568
TI  - Assays to detect and characterize synthetic agents that inhibit the ErmC
      methyltransferase.
AB  - High throughput chemical file screening with an enzymatic assay to detect
      inhibitors of the ErmC methyltransferase enzyme from macrolide-lincosamide
      streptogramin B (MLSB) resistant pathogenic bacteria identified low molecular
      weight compounds that had IC50S (50% inhibitory concentration) in the nMolar to
      microMolar range. These same inhibitors were assessed in vitro for their capacity
      to inhibit the liver enzyme, cathechol-O-methyltransferase and the prokaryotic
      enzyme, EcoRI methylase. Selective inhibitors of the ErmC methyltransferase were
      tested in tertiary assays to determine their minimal inhibitory concentrations
      (MICs), as single agents and in combination with the macrolide, azithromycin,
      against strains of pathogenic bacteria expressing MLSB-resistance. Compounds that
      were active in vitro, alone or in combination with azithromycin, against strains
      of macrolide-resistant pathogens were tested in a mouse model of infection using
      an MLSB-resistant strain of Staphylococcus aureus or a macrolide-susceptible
      strain of Streptococcus pyogenes.

PMID- 8557569
TI  - The biosynthesis of monensin-A: thymine, beta-aminoisobutyrate and methacrylate
      metabolism in Streptomyces cinnamonensis.
AB  - Feeding experiments with isotopically labelled samples of [13C,2H3-methyl]
      thymine, (R,S)-[I-13C]- and (R,S-[13C-methyl]-beta-aminoisobutyrates into
      monensin-A demonstrate that these metabolites can all contribute to the
      methylmalonyl-CoA pool in Streptomyces cinnamonensis, and implicate DNA
      catabolism as a contributory metabolic source of propionate carbon atoms for
      secondary metabolic biosynthesis. Further, these labelled compounds were
      unexpectedly incorporated into the butyrate unit of monensin-A, an observation
      which can be rationalised if beta-aminoisobutyrate is converted to methacrylyl
      CoA and then reduced to isobutyryl-CoA prior to conversion to butyryl-Coa by the
      action of isobutyryl-CoA mutase. Feeding experiments with [I-13C]- and [13C
      methyl]-methacrylates and [3-13C]-isobutyrate suggest that these metabolites
      partition similarly between the butyrate and propionate units of monensin-A
      consistent with the view that isobutyryl-CoA and methacrylyl-CoA have a close
      metabolic relationship.

PMID- 8557570
TI  - Stereostructure of Rimocidin.
AB  - NMR studies of rimocidin, consisting of DQF-COSY, ROESY, HSQC, HMBC and 1D-TOCSY
      experiments, resulted in the assignment of the absolute configuration of the
      rimocidin chiral centers as 2S, 3R, 9S, 11R, 13S, 14R, 15S, 17R, and 27R. The
      geometry of tetraene chromophore was found to be all-trans.

PMID- 8557571
TI  - Two conformers of the glycopeptide antibiotic teicoplanin with distinct ligand
      binding sites.
AB  - The clinically important vancomycin group glycopeptide antibiotics, which act by
      blocking cell wall synthesis, are crucial in the treatment of methicillin
      resistant Staphylococcus aureus. All of the group members studied so far, with
      the apparent exception of teicoplanin, enhance their antibiotic action by the
      formation of an asymmetric homodimer. Teicoplanin exists in two main conformers
      which differ by a rotation of approximately 180 degrees of a sugar residue. From
      NMR studies and molecular modelling, we present structures for the two conformers
      and conclude that they have different binding affinities for cell wall analogues.
      The two conformers of teicoplanin are closely analogous to those adopted by each
      half of the asymmetric dimers of the other vancomycin group antibiotics.

PMID- 8557572
TI  - Structure determination of ribosylated rifampicin and its derivative: new
      inactivated metabolites of rifampicin by mycobacterial strains.
AB  - Rifampicin (I) was converted into two inactivated products RIP-Ma and RIP-Mb by
      Mycobacterium smegmatis DSM43756. MS, NMR and chromatographic analysis showed the
      compounds to be 3-formyl-23-[O-(alpha-D-ribofuranosyl)]rifamycin SV (6) and 23-[O
      (alpha-D-ribofuranosyl)]rifampicin (7), respectively.

PMID- 8557573
TI  - Antibiotic GE37468 A: a novel inhibitor of bacterial protein synthesis. II.
      Structure elucidation.
AB  - GE37468 A is a novel antibiotic produced by Streptomyces sp. ATCC 55365. It has
      molecular mass 1309.48 and formula C59H52O12N14S5 and belongs to the thiazolyl
      peptide group of antibiotics. The structure was elucidated by 1H and 13C NMR and
      MS studies on intact molecule and its hydrolysis products. The antibiotic is a
      highly modified peptide containing a macrocycle and a side chain composed of a
      thiazole ring and two dehydroalanine units.

PMID- 8557574
TI  - Base-catalyzed isomerism in elfamycin antibiotics. Structures of ganefromycins
      epsilon and epsilon 1.
AB  - The structures of ganefromycins epsilon (2a) and epsilon 1 (2b) have been
      determined by spectroscopic techniques. The compounds are isomeric deoxygenated
      precursors of the parent antibiotics ganefromycins alpha and beta. The nature of
      the isomerism was determined by chemical interconversion experiments and
      spectroscope analysis to be a change in configuration at C-21. Evidence is
      provided for other cases of this type of isomerism in the elfamycin class of
      antibiotics.

PMID- 8557575
TI  - Chemical modification of tazobactam. Synthesis of 2 beta-[(4-substituted)-1,2,3
      triazol-1-yl]methyl penicillanic acid sulfone derivatives.
AB  - A series of 2 beta-[(4-substituted)-1,2,3-triazol-1-yl] methyl penicillanic acid
      sulfones was synthesized as beta-lactamase inhibitors. Many of these compounds
      showed good in vitro inhibitory activity against penicillinase, cefotaximase and
      plasmid-mediated class III TEM enzymes, but exhibited weaker cephalosporinase
      inhibition. One member in this series--2 beta-[(4-pyridiniummethyl)-1,2,3-triazol
      1-yl]-6,6-dihydropenicillanate 1,1-dioxide (12a), when tested in combination
      with piperacillin, showed excellent synergistic activity against microorganisms
      producing plasmid-mediated enzymes, but had insufficient activity against
      microorganisms producing chromosomally mediated class I enzymes.

PMID- 8557576
TI  - Derivatives of tetrodecamycin.
AB  - The derivatives of tetrodecamycin (1), being introduced acyl, carbamoyl and alkyl
      groups at 14-hydroxyl group and modified at exo-methylene group, were synthesized
      and evaluated on their antibacterial activities. Although 14-O-substituted
      tetrodecamycins (3 approximately 19) showed weak activity against Pasteurella
      piscicida, they were more active against Gram-positive bacteria than 1. Among
      them, 15 showed approximately 10-fold higher activity than 1. The derivatives (20
      approximately 23) modified at 4 or 5 positions had moderate antibacterial
      activity. The absolute structure of 4(R),5-dibromotetrodecamycin (23) was
      determined by X-ray crystallographic analysis.

PMID- 8557577
TI  - The chemistry of pseudomonic acid. Part 14. Synthesis and in vivo biological
      activity of heterocyclyl substituted oxazole derivatives.
AB  - Semisynthetic analogues of pseudomonic acid A have been prepared containing a
      heterocyclyl substituted oxazole. Derivatives in which the heterocycle was
      thiophene, furan, pyridine, or isoxazole showed good antibacterial potency and
      were further evaluated in vivo. Both pharmacokinetic parameters and oral activity
      against an experimental intraperitoneal sepsis were superior to results obtained
      from previously described pseudomonic acid A derivatives.

PMID- 8557578
TI  - Thermorubin and 2-hydroxyphenyl acetic acid, aldose reductase inhibitors.

PMID- 8557580
TI  - 2-Demethylazalomycins F4a and F5a, two new antifungal metabolites from
      Actinomycete sp. HIL Y-9120362.

PMID- 8557579
TI  - 27-O-demethylrapamycin, an immunosuppressant compound produced by a new strain of
      Streptomyces hygroscopicus.

PMID- 8557581
TI  - Phencomycin, a new antibiotic from a Streptomyces species HIL Y-9031725.

PMID- 8557582
TI  - Protein tyrosine kinase and protein kinase C inhibition by fungal anthraquinones
      related to emodin.

PMID- 8557583
TI  - Characterization of a cinodine-resistant mutant of Escherichia coli.

PMID- 8557584
TI  - Eulicin inhibits human immunodeficiency virus infection and replication.

PMID- 8557585
TI  - Effects of a beta-lactamase inhibitor, sulbactam, on the activity of carbapenems
      against Pseudomonas aeruginosa.

PMID- 8557586
TI  - RES-701-2, a novel and selective endothelin type B receptor antagonist produced
      by Streptomyces sp. II. Determination of the primary structure.

PMID- 8557587
TI  - Studies on new catechol containing cephalosporins. I. Synthesis and structure
      activity relationships of cephalosporins having a catechol moiety at the C-3
      position.

PMID- 8557588
TI  - Studies on new catechol containing cephalosporins. II. Synthesis and structure
      activity relationships of cephalosporins having a catechol moiety at the C-7
      position.

PMID- 8557589
TI  - Novel neuronal cell protecting substances, aestivophoenins A and B, produced by
      Streptomyces purpeofuscus.

PMID- 8557590
TI  - Tryprostatins A and B, novel mammalian cell cycle inhibitors produced by
      Aspergillus fumigatus.

PMID- 8557591
TI  - Liposidolide A, a new antifungal macrolide antibiotic.

PMID- 8557593
TI  - Stachybocins, novel endothelin receptor antagonists, produced by Stachybotrys sp.
      M6222. II. Structure determination of stachybocins A, B and C.
AB  - The structures of stachybocins A, B and C, new endothelin receptor antagonist,
      were determined by NMR spectral analysis using pulse-field-gradient technique.
      Stachybocin A consists of two spirobenzofuran units each fused to a substituted
      decalin, which were connected by a lysine residue. Stachybocins B and C are
      derivatives of stachybocin A with an additional hydroxy group at the same
      position in the different decalin unit.

PMID- 8557592
TI  - Stachybocins, novel endothelin receptor antagonists, produced by Stachybotrys sp.
      M6222. I. Taxonomy, fermentation, isolation and characterization.
AB  - Stachybocins A, B and C, novel endothelin (ET) receptor antagonists, were
      isolated from the culture filtrate of Stachybotrys sp. M6222. They were extracted
      with ethyl acetate and then purified by alumina and silica gel column
      chromatographies. The molecular formulae of stachybocins were determined to be
      C52H70N2O10 (stachybocin A) and C52H70N2O11 (stachybocins B and C). It was
      supposed that they consisted of spirobenzofuran and terpene units from NMR
      spectra. They showed the inhibitory activity of 125I-ET-1 binding to rate ETA,
      human ETA and human ETB receptors.

PMID- 8557594
TI  - RES-1214-1 and -2, novel non-peptidic endothelin type A receptor antagonists
      produced by Pestalotiopsis sp.
AB  - RES-1214-1 and -2, novel and non-peptidic endothelin antagonists, were isolated
      from the cultured broth of a fungus, Pestalotiopsis sp. RE-1214. RES-1214-1 and 
      2 selectivity inhibited the ET-1 binding to endothelin type A receptor (ETA
      receptor) with IC50 values of 1.5 microM and 10 microM, respectively. RES-1214-1
      and -2 inhibited the increase in intracellular Ca2+ concentration elicited by 1
      nM ET-1 in A10 cells. Taxonomy of producing strains, fermentation, isolation,
      structural determination, and biochemical properties of RES-1214-1 and-2 are
      described.

PMID- 8557595
TI  - Bassiatin, a new platelet aggregation inhibitor produced by Beauveria bassiana K
      717.
AB  - A new platelet aggregation inhibitor, bassiatin, was isolated from the cultured
      broth of Beauveria bassiana which had been isolated from a soil sample collected
      in Yunnan province, China. The structure of bassiatin was determined to be (3S,
      6R)-4-methyl-6-(1-methylethyl)-3-phenylmethyl-1, 4-perhydrooxazine-2,5-dione by
      NMR analysis, X-ray crystallographic analysis and chemical synthesis. Bassiatin
      inhibited ADP-induced aggregation of rabbit platelets with the IC50 being 1.9 x
      10(-4) M.

PMID- 8557596
TI  - Phenopyrrozin, a new radical scavenger produced by Penicillium sp. FO-2047.
AB  - A new radical scavenger, named phenopyrrozin, was isolated from the culture broth
      of Penicillium sp. FO-2047. Phenopyrrozin was purified from whole broth solvent
      extraction, silica gel chromatography, and HPLC. The structure of phenopyrrozin
      was elucidated as 5,6,7,7a-tetrahydro-2-hydroxy-1-phenyl-3H-pyrrolizin-3-one. The
      IC50 of phenopyrrozin against lipid peroxidation induced by Cr2K2O7 was 73
      micrograms/ml. Phenopyrrozin also reduced chromosomal aberrations induced by
      paraquat.

PMID- 8557597
TI  - Inhibition of acyl-CoA: cholesterol acyltransferase by isohalobacillin, a complex
      of novel cyclic acylpeptides produced by Bacillus sp. A1238.
AB  - A complex of metabolites consisting of two isomeric cyclic acylpeptides was
      isolated from a culture of Bacillus sp. A1238 by successive chromatographies on
      Amberlite XAD-7, silica gel and silica ODS columns. By a combination of
      spectroscopic and chemical analyses, the two subcomponents were identified as
      isomers of halobacillin, and the complex was designated isohalobacillin. Each
      molecule of isohalobacillin subcomponents contains either a 3-hydroxy-1-oxo-13
      methyltetradecyl or a 3-hydroxy-1-oxo-12 methyltetradecyl moiety in place of a 3
      hydroxy-1-oxopentadecyl moiety that is found in the halobacillin molecule. In a
      cell-free assay, isohalobacillin inhibited acyl-CoA: cholesterol acyltransferase
      by 50% at a concentration of 50 microM. When added to a culture of macrophage
      J774, the agent inhibited oxidized low density lipoprotein-induced synthesis of
      cholesteryl ester from [14C]oleate without affecting surface binding,
      internalization and degradation of the lipoprotein in the cells.

PMID- 8557598
TI  - YM-47141 and 47142, new elastase inhibitors produced by Flexibacter sp. Q17897.
      I. Taxonomy, fermentation, isolation, physico-chemical properties and biological
      activities.
AB  - In the course of our screening for elastase inhibitors from microorganism, we
      have found two new cyclic-depsipeptides designated YM-47141 and 47142. In this
      paper, we described the taxonomy of the producing organism and isolation, physico
      chemical properties, and biological activities of YM-47141 and 47142.

PMID- 8557599
TI  - YM-47141 and YM-47142, new elastase inhibitors produced by Flexibacter sp.
      Q17897. II. Structure elucidation.
AB  - YM-47141 and YM-47142 are new elastase inhibitor produced by Flexibacter sp.
      Q17897. These structures were elucidated by MS and NMR spectral analysis. YM
      47141 and YM-47142 were the cyclic peptides containing tricarbonyl moiety
      hydrated on the center carbonyl carbon in DMSO-d6.

PMID- 8557600
TI  - Macrosphelide, a novel inhibitor of cell-cell adhesion molecule. I. Taxonomy,
      fermentation, isolation and biological activities.
AB  - Potent anti-adherent activity was detected in fermentation extracts of microbial
      strain FO-5050. Active compounds designated macrosphelide A and B were isolated
      and the structure was determined to be 16-membered macrolide antibiotics
      possessing three ester bonds in the ring structure. Macrosphelide A dose
      dependently inhibited the adhesion of HL-60 cells to LPS-activated HUVEC
      monolayer (IC50, 3.5 microM); macrophelide B also inhibited HL-60 adhesion but to
      a lesser extent (IL50, 36 microM). Macrosphelide A did not show any antimicrobial
      and cytocidal activities at the concentration of 1000 micrograms/ml and 100
      micrograms/ml, respectively.

PMID- 8557601
TI  - Inhibition of c-fos proto-oncogene induction by Sch 52900 and Sch 52901, novel
      diketopiperazine produced by Gliocladium sp.
AB  - Sch 52900 (1) and Sch 52901 (2), two new inhibitors of c-fos proto-oncogene
      induction, have been isolated from the fermentation of broth of the fungal
      culture (SCF-1168), Gliocladium sp. Along with compounds 1 and 2, a known
      compound verticillin A (3) was also obtained from the culture. Structure
      elucidation of 1 and 2, accomplished by analysis of spectral data in comparison
      with the data of 3, revealed both 1 and 2 were found to be closely related to the
      verticillin family of diketopiperazines. All three compounds prevented serum
      stimulated transcription of the human c-fos promoter, using a fos/lac Z reporter
      gene assay, with IC50 values of 1.5, 18 and 0.5 microM of 1, 2 and 3,
      respectively. Northern analysis revealed the exposure of cells to compound 3
      causes inhibition of both phorbol ester-induced c-fos induction of serum-induced
      JE induction in the absence of inhibiting RNA synthesis, as measured by
      [3H]uridine incorporation. There results suggest that this class of compounds
      exerts antitumor activity by blocking a signal transduction pathway that is
      common to and necessary for the induction of at least a subset of immediate early
      genes involved in cell proliferation.

PMID- 8557602
TI  - Rakicidins, new cytotoxic lipopeptides from Micromonospora sp. fermentation,
      isolation and characterization.
AB  - The new cytotoxic agents rakicidins A and B were isolated from cultured broth of
      a Micromonospora sp. Spectroscopic and amino acid analysis has shown that
      rakicidin A is a new cyclic lipopeptide, consisting of 4-amino-penta-2,4-dienoic
      acid, 3-hydroxy-2,4,16-trimethyl-heptadecanoic acid, sarcosine, and 3
      hydroxyasparagine. Rakicidin B differs by one methylene group in the lipid side
      chain. These compounds exhibited cytotoxicity against the M109 cell line.

PMID- 8557603
TI  - Characterization of a new plasmid-mediated extended-spectrum beta-lactamase from
      Serratia marcescens.
AB  - A new extended spectrum beta-lactamase was detected in Serratia marcescens 42039
      that was isolated from urine of patients with complicated urinary tract infection
      in Japan. This stain produced three different beta-lactamase types (TEM-1, a
      cephalosporinase, and a new beta-lactamase: CKH-1). The TEM-1 and CKH-1 encoding
      genes were conjugated from S. marcescens 42039 to Escherichia coli K-12 at
      frequencies of 10(-5) to 10(-6). The MICs of beta-lactams against the
      transconjugant were: ampicillin > 1600, piperacillin 800, cephalothin 1600,
      ceftazidime 6.25, cefotaxime 100, and ceftriaxone 200 micrograms/ml. The CKH-1
      enzyme was purified to more than 90% by ion-exchange chromatography. The
      molecular weight of purified CKH-1 was 30 K dalton and the isoelectric point was
      8.2. Relative Vmax/Km values (cephaloridine = 100) of penicillin G, cephalothin,
      and oxyiminocephalosporins such as cefuroxime, ceftriaxone, and cefotaxime, were
      256, 226, 116, 87, and 49, respectively. The I50 values of tazobactam, BRL-42715,
      and clavulanic acid against CKH-1 enzyme were 0.0011, 0.0002, and 0.097 microM
      respectively. The enzymatic activity of CKH-1 was not inhibited by EDTA and anti
      TEM-1 serum. These findings indicate that CKH-1 is a member of the groups of
      class A beta-lactamases. This is the first report of a plasmid-mediated
      oxyiminocephalosporin hydrolyzing broad-spectrum beta-lactamase from clinical
      isolates of S. marcescens.

PMID- 8557604
TI  - Synthesis and protein tyrosine phosphatase inhibitory activity of dephostatin
      analogs.
AB  - We have synthesized derivatives of dephostatin, a protein tyrosine phosphatase
      (PTPase) inhibitor, to study the structure-activity relationships of this
      inhibitor. Inactive analogs revealed some insight into structural requirements or
      PTPase inhibitory activity of dephostatin. Both a nitroso group and phenolic
      hydroxyl groups were found to be essential for the inhibitory activity. Among the
      dephostatin derivative synthesized, one of the regioisomers of dephostatin showed
      PTPase inhibitory activity equivalent to that of dephostatin, and also had
      increased stability.

PMID- 8557605
TI  - Structure-antitumor activity relationship of semi-synthetic Spicamycin
      derivatives.
AB  - New derivatives of spicamycin modified at the fatty acid moieties of the molecule
      were synthesized and their structure-activity relationships were examined. The
      antitumor activity was greatly influenced by modification of the fatty acid
      moieties to tetradecadienoyl or dodecadienoyl analogues exhibiting better
      antitumor activity against COL-1 human colon cancer xenograft than SPM VIII.

PMID- 8557606
TI  - Synthesis and antibacterial activity of 2-(isoxazolidinio-5-yl)carbapenem
      derivatives.
AB  - The synthesis and antibacterial activity of the title compounds having an
      isoxazolidine ring at the C-2 position are described. These derivatives were
      synthesized by the 1,3-dipolar cycloaddition reaction of nitrone with 2-vinyl
      carbapenems. This 1,3-dipolar cycloaddition reaction proceeded regioselectively
      to give diastereomeric isomers of 2(-isoxazolidin-5-yl)carbapenems. It was
      ascertained that the antibacterial activity of 1 beta-methylcarbapenem
      derivatives was superior to that of the corresponding 1H-carbapenem derivatives,
      and between the 2-(isoxazolidin-5-yl)-1 beta-methylcarbapenems the antibacterial
      activity of the 5'R-isomer was slightly better than that of the 5' R-isomer
      slightly better than that of the 5' S-isomer.

PMID- 8557607
TI  - Structure-activity relationship of new 2-substituted penem antibiotics.
AB  - The antibacterial activities of three new penems with 4-hydroxyprolinamide, 1
      prolinamide and N-methyl-N-2-propionamide substituents, respectively, in position
      2 and of their stereoisomers were examined against Staphylococcus aureus,
      Enterococcus faecalis, Enterococcus faecium, Escherichia coli and Pseudomonas
      aeruginosa. All substitutes conferred a broad antibacterial spectrum on the penem
      moiety. Changes in stereoisomerism selectively improved the activity against E.
      coli, S. aureus or enterococci. The structure-activity relationships of each
      compound were discussed in relation to minimum inhibitory concentrations,
      penicillin-binding protein (PBP) affinity and outer membrane permeability
      coefficient in E. coli. In this microorganism, PBP 2 was the target for all
      compounds. Changes in stereoisomerism influenced the affinity for PBPs 1A/B and
      2. All antibiotics easily permeated the outer membrane of E. coli and, within
      each group of compounds, the penetration rate correlated with the antibacterial
      activity.

PMID- 8557608
TI  - Nerfilin I, a novel microbial metabolite inducing neurite outgrowth of PC12
      cells.

PMID- 8557609
TI  - Production and isolation of two novel esperamicins in a chemically defined
      medium.

PMID- 8557610
TI  - 4'-Deacetyl-(-)-griseusins A and B, new naphthoquinone antibiotics from an
      actinomycete.

PMID- 8557611
TI  - BE-24566B, a new antibiotic produced by Streptomyces violaceusniger.

PMID- 8557612
TI  - NK374200, a novel insecticidal agent from Taralomyces, found by physico-chemical
      screening.

PMID- 8557613
TI  - A simple immunoassay to detect protease inhibitors in microbial fermentation
      broths.

PMID- 8557614
TI  - Siamycins I and II, new anti-HIV-1 peptides: II. Sequence analysis and structure
      determination of siamycin I.

PMID- 8557615
TI  - Preparation of leustroducsin H and the structure-activity relationship of its
      derivatives.

PMID- 8557616
TI  - Amicenomycins A and B, new antibiotics from Streptomyces sp. MJ384-46F6.

PMID- 8557617
TI  - Hydranthomycin, a new agroactive antibiotic produced by Streptomyces sp. K93
      5305.

PMID- 8557618
TI  - Detection of Escherichia coli in potable water using direct impedance technology.
AB  - Direct impedance measurement utilizing a medium previously described as being
      specific for Escherichia coli and which contains trimethylamine N-oxide (TMAO)
      and glucuronic acid was used to detect E. coli in water samples. The system was
      compared with the Colilert presence/absence test and the United Kingdom standard
      membrane filtration technique using membrane lauryl sulphate broth. The impedance
      method correlated well with both the traditional membrane method (93%) and the
      Colilert method (93.95%) for a number of different water types. No interference
      from Citrobacter spp. (as reported in previous studies) was detected in this
      study although some Salmonella spp. did give false-positive results. The data
      presented here suggest that the use of direct impedance may offer an alternative
      to conventional methods for the detection of E. coli in water.

PMID- 8557619
TI  - Production of feruloyl/rho-coumaroyl esterase activity by Penicillium expansum,
      Penicillium brevicompactum and Aspergillus niger.
AB  - Extracellular esterase production by Penicillium expansum, Penicillium
      brevicompactum and Aspergillus niger was determined in both liquid and solid
      state culture. Methyl ferulate was used as the main carbon source in liquid
      culture whereas wheat bran and sugar beet pulp were used in solid-state culture.
      Extracted enzyme for each fungus showed activity in the presence of ONP butyrate,
      methyl ferulate, methyl coumarate and two 'natural' feruloylated carbohydrate
      esters. Higher enzyme recoveries were obtained using wheat bran in solid-state
      culture. Higher levels of feruloyl esterase activity were recovered from P.
      expansum on all feruloylated substrates than from P. brevicompactum or A. niger.
      Using ONP butyrate as substrate the pH and temperature optima for the esterases
      of both Penicillium spp. were 6.0 and 25-30 degrees C. Aspergillus niger esterase
      activity showed a broader temperature range with an optimum at 40 degrees C.

PMID- 8557620
TI  - Home access modifications: effects on community visits by people with physical
      disabilities.
AB  - We examined the effects of access modifications to home entrances of people with
      physical disabilities on their reported community outings. An interrupted time
      series design was used, in which the introduction of ramps was staggered across
      the homes of 6 people with moderate to severe mobility impairments. Four
      participants reported increases in weekly outings following installation of ramps
      at their entrances, and 2 reported a small decrease. These findings suggest that
      reducing the response requirements of access to and from the residence of people
      with mobility impairments may increase community visits, but may be insufficient
      given other environmental barriers in the community.

PMID- 8557621
TI  - Translating what we know about the context of antisocial behavior into a lower
      prevalence of such behavior.
AB  - Although we have identified many variables that affect antisocial behavior, there
      is no evidence that we have learned how to reduce the incidence of such behavior
      or the proportion of young people who repeatedly engage in antisocial behavior.
      It is appropriate, therefore, for behavioral scientists to turn some of their
      energies to research on reducing the incidence and prevalence of antisocial
      behavior. Small communities may be a particularly useful social unit in which to
      conduct experimental research. The interventions to be tested include advocacy
      and community organizing to influence communities to make validated school and
      clinical interventions widely available and to assist them in increasing other
      forms of supervision of young people and social and material support of families.
      Key components of advocacy and community organizing are suggested, and
      possibilities for research are described.

PMID- 8557622
TI  - Guilt appeals in advertising: what are their effects?
AB  - This study examined consumers' emotional responses, their attitudes toward
      advertisements and brands, attributions about the companies promoting the brands,
      and purchase intention for ads varying on level of guilt appeal. Sixty working
      mothers, a prime target of guilt appeals, participated in the study. Results
      indicated that moderate guilt appeals elicited more felt guilt in the working
      mothers than did low or high guilt appeals. Furthermore, emotional responses,
      particularly anger, mediated the relationship between level of guilt appeal and
      consumers' attitudes and corporate attributions, and an inverse relationship
      occurred between level of guilt appeal and attitudes and attributions. Purchase
      intention was affected by the level of the guilt appeal and by anger.

PMID- 8557623
TI  - Unexpected binding mode of the sulfonamide fluorophore 5-dimethylamino-1
      naphthalene sulfonamide to human carbonic anhydrase II. Implications for the
      development of a zinc biosensor.
AB  - The three-dimensional structure of human carbonic anhydrase II (CAII) complexed
      with the sulfonamide fluorophore 5-dimethylamino-1-naphthalene sulfonamide
      (dansylamide) has been determined to 2.1-A resolution by x-ray crystallographic
      methods. Unlike other arylsulfonamide inhibitors of CAII, the naphthyl ring of
      dansylamide binds in a hydrophobic pocket in the active site, making van der
      Waals contacts with Val-121, Phe-131, Val-143, Leu-198, and Trp-209.
      Interestingly, a conformational change of Leu-198 is required to accommodate
      dansylamide binding, which rationalizes the enhanced dansylamide affinity
      measured for certain Leu-198 variants (Nair, S. K., Krebs, J.F., Christianson, D.
      W., and Fierke, C. A. (1995) Biochemistry 34, 3981-3989). Modeling studies
      indicate that a second binding mode, in which the fused aromatic ring is rotated
      out of the hydrophobic pocket, is sterically feasible. Both experimentally
      observed and modeled binding modes have implications for new leads in the design
      of avid CAII inhibitors. Finally, the structure of the CAII-dansylamide complex
      has implications for its exploitation in zinc biosensor applications, and
      possible routes toward the optimization of fluorophore design are considered on
      the basis on this structure.

PMID- 8557624
TI  - The EcoRV modification methylase causes considerable bending of DNA upon binding
      to its recognition sequence GATATC.
AB  - The EcoRV methyltransferase modifies DNA by the introduction of a methyl group at
      the 6-NH2 position of the first deoxyadenosine in GATATC sequences. The enzyme
      forms a stable and specific complex with GATATC sequences in the presence of a
      nonreactive analogue, such as sinefungin, of its natural cofactor S-adenosyl-L
      methionine. Using circular permutation band mobility shift analysis (in which the
      distance between the GATATC sequence and the end of the DNA is varied) of protein
      DNA-cofactor complexes we have shown the methylase induces a bend of just over 60
      degrees in the bound DNA. This was confirmed by phasing analysis, in which the
      spacing between the GATATC site and a poly(dA) tract is varied through a helical
      turn, which showed that the orientation of the induced curve was toward the major
      groove. There was no significant difference in the bend angle measured using
      unmethylated GATATC sequences and hemimethylated sequences which contain G6-Me
      ATATC in one strand only. These are the natural substates for the enzyme. The
      EcoRV endonuclease, a very well characterized protein, served as a positive
      control. DNA bending by this protein has been previously determined both by
      crystallographic and solution methods. The two proteins bend DNA toward the major
      groove but the bend angle produced by the methylase, slightly greater than 60
      degree, is a little larger than that observed with the endonuclease, which is
      approximately 44 degrees.

PMID- 8557625
TI  - Estradiol and antiestrogens regulate a growth inhibitory insulin-like growth
      factor binding protein 3 autocrine loop in human breast cancer cells.
AB  - MCF-7 human breast cancer cells are commonly used to model tissues responsive to
      estrogens and antiestrogens. We examined the effects of estradiol and the
      antiestrogen ICI 182780 on MCF-7 cell proliferation and insulin-like growth
      factor binding protein 3 (IGFBP-3) gene expression. ICI 182780-induced growth
      inhibition was associated with increased transcription of the IG-FBP-3 gene,
      increased IGFBP-3 mRNA abundance, and increased IGFBP-3 protein accumulation in
      the conditioned medium. The growth stimulatory effect of estradiol was associated
      with opposite effects, and the correlation between cellular proliferation and
      IGFBP-3 mRNA abundance was strong (r = -0.91). Recombinant IGFBP-3 inhibited
      basal and estradiol-stimulated MCF-7 cell proliferation, and an IGFBP-3 antisense
      oligodeoxynucleotide abolished antiestrogen-induced growth inhibition. These
      results provide evidence for an estradiol and antiestrogen-regulated IGFBP-3
      growth inhibitory autocrine pathway in MCF-7 cells.

PMID- 8557626
TI  - Important role of the amino acid attached to tRNA in formylation and in
      initiation of protein synthesis in Escherichia coli.
AB  - In attempts to convert an elongator tRNA to an initiator tRNA, we previously
      generated a mutant elongator methionine tRNA carrying an anticodon sequence
      change from CAU to CUA along with the two features important for activity of
      Escherichia coli initiator tRNA in initiation. This mutant tRNA (Mi:2 tRNA) was
      active in initiation in vivo but only when aminoacylated with methionine by
      overproduction of methionyl-tRNA synthetase. Here we show that the Mi:2 tRNA is
      normally aminoacylated in vivo with lysine and that the tRNA aminoacylated with
      lysine is a very poor substrate for formylation compared with the same tRNA
      aminoacylated with methionine. By introducing further changes at base pairs 4:69
      and 5:68 in the acceptor stem of the Mi:2 tRNA to those found in the E. coli
      initiator tRNA, we show that change of the U4:A69 base pair to G4:C69 and
      overproduction of lysyl-tRNA synthetase and methionyl-tRNA transformylase results
      in partial formylation of the mutant tRNA and activity of the formyllysyl-tRNAs
      in initiation of protein synthesis. Thus, the G4: C69 base pair contributes
      toward formylation of the tRNA and protein synthesis in E. coli can be initiated
      with formyllysine. We also discuss the implications of these and other results on
      recognition of tRNAs by E. coli lysyl-tRNA synthetase and on competition in cells
      among aminoacyl-tRNA synthetases.

PMID- 8557627
TI  - Interleukin-1 enhances pancreatic islet arachidonic acid 12-lipoxygenase product
      generation by increasing substrate availability through a nitric oxide-dependent
      mechanism.
AB  - Interleukin-1 (IL-1) impairs insulin secretion from pancreatic islets and may
      contribute to the pathogenesis of insulin-dependent diabetes mellitus. IL-1
      increases islet expression of nitric oxide (NO) synthase, and the resultant
      overproduction of NO participates in inhibition of insulin secretion because NO
      synthase inhibitors, e.g. NG-monomethyl-arginine (NMMA), prevent this inhibition.
      While exploring effects of IL-1 on islet arachidonic acid metabolism, we found
      that IL-1 increases islet production of the 12-lipoxygenase product 12
      hydroxyeicosatetraenoic acid 12-(HETE). This effect requires NO production and is
      prevented by NMMA. Exploration of the mechanism of this effect indicates that it
      involves increased availability of the substrate arachidonic acid rather than
      enhanced expression of 12-lipoxygenase. Evidence supporting this conclusion
      includes the facts that IL-1 does not increase islet 12-lipoxygenase protein or
      mRNA levels and does not enhance islet conversion of exogenous arachidonate to 12
      HETE. Mass spectrometric stereochemical analyses nonetheless indicate that 12
      HETE produced by IL-1-treated islets consists only of the S-enantiomer and thus
      arises from enzyme action. IL-1 does enhance release of nonesterified
      arachidonate from islets, as measured by isotope dilution mass spectrometry, and
      this effect is suppressed by NMMA and mimicked by the NO-releasing compound 3
      morpholinosydnonimine. Although IL-1 increases neither islet phospholipase A2
      (PLA2) activities nor mRNA levels for cytosolic or secretory PLA2, a suicide
      substrate which inhibits an islet Ca(2+)-independent PLA2 prevents enhancement of
      islet arachidonate release by IL-1. IL-1 also impairs esterification of
      [3H8]arachidonate into islet phospholipids, and this effect is prevented by NMMA
      and mimicked by the mitochondrial ATP-synthase inhibitor oligomycin. Experiments
      with exogenous substrates indicate that NMMA does not inhibit and that the NO
      releasing compound does not activate islet 12-lipoxygenase or PLA2 activities.
      These results indicate that a novel action of NO is to increase levels of
      nonesterified arachidonic acid in islets.

PMID- 8557629
TI  - Overexpression, purification, and properties of Escherichia coli ribonuclease II.
AB  - Ribonuclease II (RNase II) is a major exonuclease in Escherichia coli that
      hydrolyzes single-stranded polyribonucleotides processively in the 3' to 5'
      direction. To understand the role of RNase II in the decay of messenger RNA, a
      strain overexpressing the rnb gene was constructed. Induction resulted in a 300
      fold increase in RNase II activity in crude extracts prepared from the
      overexpressing strain compared to that of a non-overexpressing strain. The
      recombinant polypeptide (Rnb) was purified to apparent homogeneity in a rapid,
      simple procedure using conventional chromatographic techniques and/or fast
      protein liquid chromatography to a final specific activity of 4,100 units/mg.
      Additionally, a truncated Rnb polypeptide was purified, solubilized, and
      successfully renatured from inclusion bodies. The recombinant Rnb polypeptide was
      active against both [3H]poly(A) as well as a novel (synthetic partial duplex) RNA
      substrate. The data show that the Rnb polypeptide can disengage from its
      substrate upon stalling at a region of secondary structure and reassociate with a
      new free 3'-end. The stalled substrate formed by the dissociation event cannot
      compete for the Rnb polypeptide, demonstrating that duplexed RNAs lacking 10
      protruding unpaired nucleotides are not substrates for RNase II. In addition, RNA
      that has been previously trimmed back to a region of secondary structure with
      purified Rnb polypeptide is not a substrate for polynucleotide phosphorylase-like
      activity in crude extracts. The implications for mRNA degradation and the
      proposed role for RNase II as a repressor of degradation are discussed.

PMID- 8557628
TI  - The mouse zic gene family. Homologues of the Drosophila pair-rule gene odd
      paired.
AB  - The mouse Zic gene, which encodes a zinc finger protein, is expressed in the
      developing or matured central nervous system in a highly restricted manner. We
      identified two novel Zic-related genes (Zic2, Zic3) through genomic and cDNA
      cloning. Both genes are highly similar to Zic(1), especially in their zinc finger
      motif. A comparison of genomic organization among the three Zic genes showed that
      they share common exon-intron boundaries and belong to the same gene family .
      Zic1, Zic2, and Zic3 were determined to mouse chromosome 9, 14, and X using an
      interspecific backcross panel. Northern blotting and ribonuclease protection
      showed that Zic2 and Zic3 are expressed in a restricted manner in the cerebellum
      at the adult stage. However, the temporal profile of the mRNA expression in the
      developing cerebella differ in the three Zic genes. Furthermore, we found that
      the Drosophila pair-rule gene, odd-paired is highly homologous to the Zic gene
      family. The similarity was not only the zinc finger motif, but also the exon
      intron boundary was the same as those of mouse Zic gene family. These findings
      suggest that the Zic gene family and Drosophila odd-paired are derived from a
      common ancestral gene.

PMID- 8557630
TI  - Sp1-mediated transcriptional activation of the human Pi class glutathione S
      transferase promoter.
AB  - Previous studies in this laboratory have identified an essential AP-1 recognition
      sequence (C1 region; -69 to -63) in th human Pi class glutathione s-transferase
      (GSTP1) promoter and a negatively acting regulatory element (-105 to -86) that
      acts to suppress GSTP1 transcription in the human mammary carcinoma cell line,
      MCF7 (1). The data presented here further delineate the functional
      characteristics of the GSTP1 promoter by examining the significance of two
      potential binding sites for the transcription factor, Sp1 (-57 to -49 and -47 to 
      39). The introduction of mutations within these Sp1-like elements and the use of
      Sp1 antisera in electrophoretic mobility shift assays demonstrated that Sp1 was
      bound to this region of the GSTP1 promoter in three different cell lines, MCF7,
      VCREMS, and EJ. Moreover, these in vitro studies indicated that only one of the
      two putative Sp1 response elements was utilized. Transient transfection assays
      using GSTP1 promoter constructs that incorporated mutations of the Sp1 elements
      clearly demonstrated that binding of Sp1 to the GSTP1 promoter was absolutely
      required for optimal levels of GSTP1 transcription. In particular, disruption of
      the distal Sp1 recognition motif (-57 to -49) markedly reduced GSTP1 promoter
      activity in each cell line, thus indicating preferential binding of Sp1 to the
      distal site. However, insertion of the repressor binding site (-105 to -86) into
      these constructs suggested that Sp1 was not involved in mediating the suppressive
      effects of the GSTP1 transcriptional repressor in MCF7 cells, because inhibition
      of Sp1 binding did not alleviate repressor activity. Therefore, these studies
      provide strong evidence that Sp1 plays a central role in regulating basal levels
      of GSTP1 transcription.

PMID- 8557631
TI  - The beta-adrenergic receptor is a substrate for the insulin receptor tyrosine
      kinase.
AB  - G-protein-linked receptors and intrinsic tyrosine-kinase growth receptors
      represent two prominent modalities in cell signaling. Cross-regulation among
      members of both receptor superfamilies has been reported, including the counter
      regulatory effects of insulin on beta-adrenergic catecholamine action. Cells
      stimulated by insulin show loss of function and increased phosphotyrosine content
      of beta 2-adrenergic receptors. Phosphorylation of tyrosyl residues 350/354 of
      beta 2-adrenergic receptors is obligatory for counter-regulation by insulin
      (Karoor, V., Baltensperger, K., Paul, H., Czech, M., and Malbon, C. C. (1995) J.
      Biol. Chem. 270, 25305-25308), suggesting the hypothesis that G-protein-linked
      receptors themselves may act as substrates for the insulin receptor and other
      growth factor receptors. This hypothesis was evaluated directly using recombinant
      human insulin receptor, hamster beta 2-adrenergic receptor, and an vitro
      reconstitution and phosphorylation assay. Insulin is shown to stimulate insulin
      receptor-catalyzed phosphorylation of the beta 2-adrenergic receptor.
      Phosphoamino acid analysis establishes that insulin receptor-catalyzed
      phosphorylation of the beta 2-adrenergic receptor in vitro is confined to
      phosphotyrosine. High pressure liquid chromatography and two-dimensional mapping
      reveal insulin receptor-catalyzed phosphorylation of the beta 2-adrenergic
      receptor at residues Tyr132/Tyr141, Tyr350/Tyr354, and Tyr364, known sites of
      phosphorylation in response to insulin in vivo. Insulin-like growth factor-I
      receptor as well as the insulin receptor displays the capacity to phosphorylate
      the beta 2-adrenergic receptor in vitro, establishing a new paradigm, i.e. G
      protein-linked receptors acting as substrates for intrinsic tyrosine kinase
      growth factor receptors.

PMID- 8557632
TI  - Alternative splicing of cAMP-specific phosphodiesterase mRNA transcripts.
      Characterization of a novel tissue-specific isoform, RNPDE4A8.
AB  - In order to characterize the structure and regulation of members of the cAMP
      specific phosphodiesterase (PDE) family (Type IV PDEs; PDE4 family), we have
      cloned from the rat a cDNA, pRPDE39, encoding a novel member of this family,
      which we call RNPDE4A8. Sequencing of the pRPDE39 cDNA shows it to be encoded by
      the rat PDE4A gene, but to differ from two other PDE4A transcripts, RD1 (pRPDE8;
      RNPDE4A1) and pRPDE6 (RNPDE4A5), by the presence of a unique region at its 5'
      end, consistent with alternative mRNA splicing. The pRPDE39 cDNA encodes a
      predicted protein of 763 amino acids, of which all but 21, located at the extreme
      amino terminus, are found in the pRPDE6 protein. Expression of pRPDE39 in COS
      cells produced a protein of 98 +/- 1.4 kDa, as determined by immunoblotting with
      an antiserum specific to the carboxyl-terminal regions of all PDE4A proteins,
      compared to a predicted value of 87.5 kDa. RNase protection analysis detected
      pRPDE39 mRNA only in testis. Immunoblotting of testis extracts demonstrated two
      bands of 97 +/- 2 and 87 +/- 3 kDa, the larger of which co-migrated with the band
      seen in COS cells expressing pRPDE39. COS cell expressed pRPDE39 partitioned
      between a high speed pellet (particulate) fraction (15% of protein; 8% of
      activity) and a cytosolic fraction. The particulate fraction had a Km for cAMP of
      3.3 +/- 0.6 microM, and the cytosolic fraction a Km of 5.4 +/- 2.8 microM. The
      Vmax values for the pRPDE39 protein, relative to the RD1 protein, were 0.16 +/-
      0.06 and 0.29 +/- 0.05 for the particulate and cytosolic forms, respectively. The
      pRPDE39-encoded PDE activity could not be removed from the particulate fraction
      by high salt concentrations, or by nonionic detergents. The pRPDE39-encoded
      enzyme was inhibited by rolipram at an IC50 of 0.5 +/- 0.2 microM for the
      particulate form and 1.0 +/- 0.2 microM for the cytosolic form, which are values
      typical of PDE4 family members. The highly tissue-specific distribution of the
      pRPDE39 mRNA suggest that the pRPDE39 protein functions to modulate a cAMP
      signaling pathway that is present largely, if not exclusively, in the testis.

PMID- 8557633
TI  - Analogs of human plasminogen that are labeled with fluorescence probes at the
      catalytic site of the zymogen. Preparation, characterization, and interaction
      with streptokinase.
AB  - Fluorescent analogs of the proteinase zymogen, plasminogen (Pg), which are
      specifically inactivated and labeled at the catalytic site have been prepared and
      characterized as probes of the mechanisms of Pg activation. The active site
      induced non-proteolytically in Pg by streptokinase (SK) was inactivated
      stoichiometrically with the thioester peptide chloromethyl ketone. N alpha
      [(acetylthio)acetyl]-(D-Phe)-Phe-Arg-CH2Cl; the thiol group generated
      subsequently on the incorporated inhibitor with NH2OH was quantitatively labeled
      with the fluorescence probe, 2-((4'-iodoacetamido)anilino)naphthalene-6-sulfonic
      acid; and the labeled Pg was separated from SK. Cleavage of labeled [Glu]Pg1 by
      urokinase-type plasminogen activator (uPA) was accompanied by a fluorescence
      enhancement (delta Fmax/Fo) of 2.0, and formation of 1% plasmin (Pm) activity.
      Comparison of labeled and native [Glu]Pg1 as uPA substrates showed that
      activation of labeled [Glu]Pg1 generated [Glu]Pm1 as the major product, while
      native [Glu]Pg1 was activated at a faster rate and produced [Lys]Pm1 because of
      concurrent proteolysis by plasmin. When a mixture of labeled and native Pg was
      activated, to include plasmin-feedback reactions, the zymogens were activated at
      equivalent rates. The lack of potential proteolytic activity of the Pg
      derivatives allowed their interactions with SK to be studied under equilibrium
      binding conditions. SK bound to labeled [Glu]Pg1, and [Lys]Pg1 with dissociation
      constants of 590 +/- 110 and 110 and 11 +/- 7 nM, and fluorescence enhancements
      of 3.1 +/- 0.1 and 1.6 +/- 0.1, respectively. Characterization of the interaction
      of SK with native [Glu]Pg1 by the use of labeled [Glu]Pg1 as a probe indicated a
      approximately 6-fold higher affinity of SK for the native Pg zymogen compared to
      the labeled Pg analog. Saturating levels of epsilon-aminocaproic acid reduced the
      affinity of SK for labeled [Glu]Pg1 by approximately 2-fold and lowered the
      fluorescence enhancement to 1.8 +/- 0.1, whereas the affinity of SK for labeled
      [Lys]Pg1 was reduced by approximately 98-fold with little effect on the
      enhancement. These results demonstrate that occupation of lysine binding sites
      modulates the affinity of SK for Pg and the changes in the environment of the
      catalytic site associated with SK-induced conformational activation. Together,
      these studies show that the labeled Pg derivatives behave as analogs of native Pg
      which report functionally significant changes in the environment of the catalytic
      site of the zymogen.

PMID- 8557634
TI  - Protein SIC, a novel extracellular protein of Streptococcus pyogenes interfering
      with complement function.
AB  - The human pathogen Streptococcus pyogenes possesses a chromosomal region, the mga
      regulon, that contains co-regulated genes important to the virulence of these
      bacteria. A novel gene located in the mga regulon of a S. pyogenes strain of
      serotype M1 was cloned and sequenced. It translates into a protein of 305 amino
      acid residues, including a signal sequence of 32 amino acids and a central region
      consisting of three tandem repeats. The sequence represents a novel structure
      with no significant homology to any previously published sequence. The protein
      was purified from the streptococcal culture media where it is present in
      substantial amounts. Affinity chromatography of human plasma on Sepharose coupled
      with the protein specifically absorbed two plasma proteins which were identified
      as clusterin and histidine-rich glycoprotein (HRG). The interactions between the
      streptococcal protein and the plasma proteins were further characterized using
      purified clusterin and HRG. Inhibition experiments indicated that they have
      affinity for overlapping or closely located sites in the streptococcal protein.
      Both clusterin and HRG are regulators of the membrane attack complex (C5b-C9) of
      complement. When the streptococcal protein was added to serum, complement
      mediated lysis of sensitized sheep erythrocytes and guinea pig erythrocytes was
      inhibited. In addition, the streptococcal protein was incorporated into C5b-C9 in
      serum, indicating the location of its action. The name, protein SIC,
      streptococcal inhibitor of complement-mediated lysis, is therefore suggested for
      this novel protein. The occurrence of protein SIC and its gene was investigated
      in a collection of S. pyogenes strains comprising 55 different M serotypes. Only
      M1 and M57 strains were positive in this screening, indicating that protein SIC
      could be a virulence determinant. Thus, during recent years, the M1 serotype has
      been connected with a world-wide increase of severe and toxic S. pyogenes
      infections.

PMID- 8557635
TI  - Splice variants of type VIII adenylyl cyclase. Differences in glycosylation and
      regulation by Ca2+/calmodulin.
AB  - Three alternatively spliced type VIII adenylyl cyclase messages have been
      identified by cDNA cloning and amplification from rat brain cDNA. Type VIII-A was
      previously referred to simply as type VIII (Cali, J. J., Zwaagstra, J. C., Mons,
      N., Cooper, D. M. F., and Krupinski, J. (1994) J. Biol. Chem. 269, 12190-12195).
      The types VIII-B and -C cDNAs differ from that of type VIII-A by deletion of 90
      and 198 base pair exons, respectively, which encode a 30-amino acid extracellular
      domain with two consensus sites for N-linked glycosylation and a 66-amino acid
      cytoplasmic domain. Stable expression of types VIII-A, -B, and -C cDNAs in human
      embryonal kidney 293 (HEK-293) cells leads to the appearance of novel proteins,
      which are recognized by type VIII-specific antibodies and which co-migrate with
      immunoreactive species detected on immunoblots of rat brain membranes. Types VIII
      A and -C are modified by N-linked glycosylation, while type VIII-B is insensitive
      to treatment with N-glycosidase F. An influx of extracellular Ca2+ stimulates
      cAMP accumulation in HEK-293 cells stably expressing type VIII-A, -B, or -C, but
      not in control cells. Adenylyl cyclase activity of each of the variants is
      stimulated by Ca2+/calmodulin and the EC50 for activation of type VIII-C is one
      fourth of that for either type VIII-A or -B. Type VIII-C also has a distinct Km
      for substrate, which is approximately 4-12-fold higher than that for types VIII-A
      or -B depending on whether Mn2+ or Mg2+ is the counterion for ATP. The
      differences in the structural and enzymatic properties of these three variants
      are discussed.

PMID- 8557636
TI  - Further characterization of proteins associated with elastic fiber microfibrils
      including the molecular cloning of MAGP-2 (MP25)
AB  - Together with the 31-kDa microfibril-associated glycoprotein (MAGP), four
      polypeptides designated MP340 (340 kDa), MP78 (78 kDa), MP70 (70 kDa), and MP25
      (25 kDa) have previously been identified in tissue extracts designed specifically
      to solubilize the microfibrillar component of elastic fibers. In the present
      study, both MP78 and MP70 were shown to be forms of a protein which is closely
      related to the human protein beta ig-h3, and MP340 was confirmed to be the bovine
      form of fibrillin-1. Peptide sequences from MP25 proved to be unique, and
      affinity-purified anti-MP25 antibodies were shown, by immunofluorescence and
      immunoelectron microscopy, to localize specifically to the elastin-associated
      microfibrils. This confirmed that MP25 was a distinct component of these
      structures. Expression screening of nuchal ligament cDNA libraries yielded a
      cDNA, cM10A (770 base pairs) which encodes amino acid sequences matching those of
      the MP25 peptides. Further library screening with cM10A identified cDNAs which
      encode the complete primary structures of bovine and human MP25. Bovine and human
      MP25 were found to be around 80% homologous and contain 170 and 173 amino acids,
      respectively. Data base searches revealed that MP25 had significant similarity of
      structure only with MAGP, indicating that the two proteins form a new family of
      microfibrillar proteins. In acknowledgment, MP25 has been formally renamed MAGP
      2, and MAGP is referred to as MAGP-1. The close similarity between the two
      proteins (57%) is confined to a central region of 60 amino acids where there is
      precise alignment of 7 cysteine residues. Elsewhere the MAGP-2 molecule is rich
      in serine and threonine residues and contains an RGD motif. MAGP-2 lacks the
      proline-, glutamine-, and tyrosine-rich sequences and a hydrophobic carboxyl
      terminus, characteristic of MAGP-1. These structural differences suggest that
      MAGP-2 has some functions which are distinct from those of MAGP-1. The locus of
      the human MAGP-2 gene was identified on chromosome 12 in the region of 12p12.3
      12p13.1.

PMID- 8557637
TI  - Zinc fingers 1-7 of EVI1 fail to bind to the GATA motif by itself but require the
      core site GACAAGATA for binding.
AB  - EVI1 is a zinc finger oncoprotein that binds via fingers 1-7 to the sequence
      GACAAGATAA. The target genes on which EVI1 acts are unknown. This binding motif
      overlaps with that for the GATA transcription factors, (T/A)GATA(A/G), and GATA-1
      can bind to and activate transcription via a GACAAGATAA motif. The possibility
      has been raised that, when overexpressed in leukemogenesis, EVI1 may function by
      interfering with the differentiation-promoting action of GATA factors. To explore
      this, we have assessed the affinity of EVI1 for the GATA binding sites derived
      from erythroid-specific GATA-1 target genes, and found only low affinity
      interactions. We examined the contacts between EVI1 and DNA by methylation
      interference studies, which revealed extensive contacts between EVI1 and its
      binding site. The importance of the contacts for high affinity binding was shown
      by in vitro quantitative gel shift studies and in vivo cotransfection studies. To
      examine what types of sequences from mouse genomic DNA bind to EVI1, we isolated
      and sequenced five EVI1-binding fragments, and each showed the GACAAGATA site.
      The data presented contribute to our knowledge of the binding specificity of
      EVI1, and yield a clearer picture of what sequences can, and cannot, act as
      targets for EVI1 action.

PMID- 8557638
TI  - Regulation of cytokine-inducible nitric oxide synthase in cardiac myocytes and
      microvascular endothelial cells. Role of extracellular signal-regulated kinases 1
      and 2 (ERK1/ERK2) and STAT1 alpha.
AB  - Adult rat ventricular myocytes and cardiac microvascular endothelial cells (CMEC)
      both express an inducible nitric oxide synthase (iNOS or NOS2) following exposure
      to soluble inflammatory mediators. However, NOS2 gene expression is regulated
      differently in response to specific cytokines in each cell type. Interleukin-1
      beta (IL-1 beta) induces NOS2 in both, whereas interferon gamma (IFN gamma)
      induces NOS2 expression in myocytes but not in CMEC. Therefore, we examined the
      specific signal transduction pathways that could regulate NOS2 mRNA levels,
      including activation of 44- and 42-kDa mitogenactivated protein kinases (MAPKs;
      ERK1/ERK2) and STAT1 alpha, a transcriptional regulatory protein linked to cell
      membrane receptors. Although IL-1 beta treatment increased ERK1/ERK2 activities
      in both cell types, IFN gamma activated these MAPKs only in myocytes. STAT1 alpha
      phosphorylation, consistent with IFN gamma-induced signaling, was readily
      apparent in both cell types, and binding of activated STAT1 alpha from
      cytoplasmic or nuclear fractions from IFN gamma-treated adult myocytes to a sis
      inducible element could be demonstrated by gel-shift assay. The farnesyl
      transferase inhibitor BZA-5B blocked activation of ERK1/ERK2 and induction of
      NOS2 by IFN gamma and IL-1 beta in myocytes. IL-1 beta and IFN gamma-induced NOS2
      gene expression in myocytes was also down-regulated by both protein kinase C
      (PKC) desensitization and by the PKC inhibitor bisindolylmaleimide, implicating
      PKC-linked activation of Ras or Raf in the induction of NOS2 by IL-1 beta and IFN
      gamma in cardiac muscle cells. In CMEC, the MAPK kinase inhibitor PD 98059
      blocked activation of ERK1/ERK2 and down-regulated IL-1 beta-mediated NOS2
      induction, whereas activation of ERK2 in the absence of cytokines by okadaic
      acid, an inhibitor of phosphoserine protein phosphatases, also induced NOS2 mRNA.
      These data demonstrate that ERK1/ERK2 activation appears to be necessary for the
      induction of NOS2 by IL-1 beta and IFN gamma in cardiac myocytes and CMEC. In the
      absence of ERK1/ERK2 activation by IFN gamma in CMEC, phosphorylation of STAT1
      alpha is not sufficient for NOS2 gene expression. These overlapping yet distinct
      cellular responses to specific cytokines may serve to target NOS2 gene expression
      to specific cells or regions within the heart and also provide for rapid
      escalation of NO production if required for host defense.

PMID- 8557639
TI  - Purification, microsequencing, and immunolocalization of p36, a new interferon
      alpha-induced protein that is associated with human lupus inclusions.
AB  - The trace interferon-alpha-induced protein, p36, was induced in Raji cells in
      association with lupus inclusions. It was solubilized in a nonionic detergent
      buffer, enriched by differential centrifugation and by preparative isoelectric
      focusing, and purified to homogeneity on two-dimensional protein gels. Failure to
      obtain N-terminal amino acid sequence, however, suggested a blocked alpha-amino
      group. Sequences of six tryptic peptides, 13-19 amino acids in length, were
      obtained after digestion, microbore-high performance liquid chromotography
      purification, and chemical sequence analysis. None of the six sequences, which
      represented approximately 25% of the entire protein, shared any meaningful
      homologies with entries in protein sequence repositories. Raji-cell p36 was shown
      in Western blots with antipeptide antibodies to be induced at least 400-fold and
      by immunofluorescence microscopy to co-localize with the endoplasmic reticulum
      resident protein, protein disulfide isomerase. These results show that p36 is a
      new interferon-alpha-induced protein that localizes in the endoplasmic reticulum,
      the cell region in which the lupus inclusions form, and that p36 is probably
      physically associated with the lupus inclusions.

PMID- 8557640
TI  - The role of individual cysteine residues in the activity of Escherichia coli
      RNase T.
AB  - Escherichia coli RNase T, which is responsible for the 3' processing and end
      turnover of tRNA and the maturation of 5 S RNA, is extremely sensitive to
      sulfhydryl reagents and to oxidation, suggesting a role for cysteine residues in
      its activity. Titration of homogeneous RNase T with 5,5'-dithiobis-(2
      nitrobenzoic acid) revealed that the 4 cysteine residues present in each of the
      two protein subunits are in a reduced form and that 1 or 2 of them are important
      for activity. To identify these residue(s), each of the cysteines in RNase T was
      changed individually to either serine or alanine. The serine mutant at position
      168 is greatly reduced in RNase T activity both in vivo and in vitro; likewise,
      the serine mutant at position 112 and the alanine mutants at positions 112 and
      168 also display decreased RNase T activity. Mutations at the other cysteine
      positions show little or no change. Kinetic analyses of the mutant enzymes showed
      that the Km values of C168S and C168A are increased considerably, whereas their
      Vmax values are reduced only slightly compared to the wild type enzyme. The other
      mutant enzymes are little changed. Additional amino acid replacements at position
      168 showed that the in vivo and in vitro activities of RNase T are in the order
      Cys approximately Val > Ala >> Ser >> Asn approximately Asp, which closely
      follows the relative hydrophobicity of these amino acid residues. However, the
      affinity for tRNA, determined by fluorescence quenching, is not altered in C168S,
      suggesting that Cys-168 is not directly involved in substrate binding.
      Interestingly, proteins altered at position 168 showed increased temperature
      sensitivity as the residue at that position became less hydrophobic. These data
      indicate that Cys-168 contributes a hydrophobic group that influences the
      structure and ultimately the catalytic activity of RNase T.

PMID- 8557641
TI  - Escherichia coli RNase T functions in vivo as a dimer dependent on cysteine 168.
AB  - It was shown that Cys-168 is required for RNase T function and thermostability
      and that its hydrophobic properties are important for this role (Li, Z., Zhan,
      L., and Deutscher, M. P. (1996) J. Biol Chem. 271, 1127-1132). To understand the
      molecular basis for these findings, further studies of Cys-168 and RNase T
      structure were carried out. Treatment of RNase T with the sulfhydryl-modifying
      agent 5,5'-dithiobis-(2-nitrobenzoic acid) leads not only to inactivation, but
      also to monomerization of the protein. Similarly, specifically converting Cys-168
      to either serine or asparagine leads to loss of activity and to monomer formation
      at 37 degrees C. However, at 10 degrees C the serine mutant remains as a dimer
      and retains full RNase T activity, whereas the asparagine derivative shows only a
      low level of activity and of dimer formation. These data show a strong
      correlation between activity and the dimer form of RNase T. The importance of
      dimer formation was also shown in vivo using genetic studies. An inactive mutant
      of RNase T, termed HA2, which exists as a dimer at 37 degrees C in vitro,
      completely suppresses endogenous RNase T activity in vivo and in vitro when
      introduced into a RNase T+ cell on a multicopy phagemid, most likely as a
      consequence of inactive heterodimer formation. Introduction of the HA2 gene on a
      single-copy plasmid, as expected, leads to a proportionally smaller effect on
      endogenous activity. The dominant negative effect displayed by the HA2 protein
      can be relieved by an additional mutation in HA2 RNase T that abolishes its
      ability to dimerize. An inactive mutant asparagine derivative of Cys-168, which
      also does not dimerize, also shows little of the dominant negative phenotype.
      Thus, these data demonstrate that RNase T dimerizes in vivo, that the dimer form
      is required for RNase T activity, and that Cys-168 is needed for dimerization of
      the enzyme.

PMID- 8557642
TI  - Regulation of GLUT4 gene expression by arachidonic acid. Evidence for multiple
      pathways, one of which requires oxidation to prostaglandin E2.
AB  - We have previously described the ability of arachidonic acid (AA) to regulate
      GLUT4 gene expression (Tebbey, P.W., McGowan, K.M., Stephens, J.M., Buttke, T.M.,
      and Pekala, P.H. (1994) J. Biol. Chem. 269, 639-644). Chronic exposure (48 h) of
      fully differentiated 3T3-L1 cells to AA resulted in an approximately 90%
      suppression of GLUT4 mRNA accumulation. This decrease was demonstrated to be due
      to a 50% decrease in GLUT4 gene transcription as well as a destabilization of the
      GLUT4 message (t1/2 decreased from 8.0 to 4.6 h). In the current study we have
      identified, at least in part, the mechanism by which AA exerts its effects on
      GLUT4 expression. Compatible with a cyclooxygenase mediated event, the AA-induced
      suppression of GLUT4 mRNA was abolished by pretreating the cells with the
      inhibitor, indomethacin. Consistent with this observation, exposure of the cells
      to 10 microM PGE2 mimicked the effect of AA, in contrast to products of the
      lipoxygenase pathway which were unable to suppress GLUT4 mRNA content.
      Quantification of the conversion of AA to PGE2 demonstrated a 50-fold increase in
      PGE2 released into the media within 7 h of AA addition. Cyclic AMP levels were
      also increased 50-fold with AA treatment consistent with PGE2 activation of
      adenylate cyclase. Various long chain fatty acids, including the nonmetabolizable
      analog of AA, eicosatetraenoic acid (ETYA), also decreased GLUT4 mRNA levels. The
      effect of ETYA, a potent inhibitor of both lipo- and cyclooxygenases and a potent
      activator of peroxisome proliferator activated receptors (PPARs), suggested the
      presence of a second pathway where non-metabolized fatty acid functioned to
      suppress GLUT4 mRNA levels. Further support for a PPAR-mediated mechanism was
      obtained by exposure of the cells to the classic PPAR activator, clofibrate,
      which resulted in a approximately 75% decrease in GLUT4 mRNA content. Nuclear
      extracts prepared from the adipocytes contained a protein complex that bound to
      the PPAR responsive element (PPRE) found in the promoter of the fatty acyl-CoA
      oxidase gene. When the adipocytes were treated with either AA or ETYA, binding to
      the PPRE was disrupted, consistent with an ability of these fatty acids to
      control gene expression by altering the occupation of a PPRE. However, a perfect
      PPRE has yet to be identified in the GLUT4 promoter, but this does not rule the
      possibility of a PPAR playing an indirect role in the AA-induced GLUT4 mRNA
      suppression.

PMID- 8557643
TI  - Activation-induced association of a 145-kDa tyrosine-phosphorylated protein with
      Shc and Syk in B lymphocytes and macrophages.
AB  - Engagement of many cell surface receptors results in tyrosine phosphorylation of
      an overlapping set of protein substrates. Some proteins, such as the adaptor
      protein Shc, and a frequently observed Shc-associated protein, p145, are common
      substrates in a variety of receptor signaling pathways and are thus of special
      interest. Tyrosine-phosphorylated Shc and p145 coprecipitated with anti-Shc
      antibodies following B cell antigen receptor (BCR) cross-linking or interleukin-4
      (IL-4) receptor activation in B cells, and after lipopolysaccharide (LPS)
      treatment or IgG Fc receptor (Fc gamma R) cross-linking in macrophages. In the
      case of BCR stimulation, we have shown that this represented the formation of an
      inducible complex. Furthermore, in response to LPS activation or Fc gamma R cross
      linking of macrophages and BCR cross-linking (but not IL-4 treatment) of B cells,
      we observed a similar tyrosine-phosphorylated p145 protein associated with the
      tyrosine kinase Syk. We did not detect any Shc associated with Syk, indicating
      that a trimolecular complex of Shc, Syk, and p145 was not formed in significant
      amounts. By several criteria, the Syk-associated p145 was very likely the same
      protein as the previously identified Shc-associated p145. The Syk-associated p145
      and the Shc-associated p145 exhibited identical mobility by SDS-polyacrylamide
      gel electrophoresis and identical patterns of induced tyrosine phosphorylation.
      The p145 protein that coprecipitated with either Shc or Syk bound to a GST-Shc
      fusion protein. In addition, a monoclonal antibody developed against Shc
      associated p145 also immunoblotted the Syk-associated p145. The observations that
      p145 associated with both Shc and Syk proteins, in response to stimulation of a
      variety of receptors, suggest that it plays an important role in coordinating
      early signaling events.

PMID- 8557644
TI  - The product of the Drosophila gene, Glued, is the functional homologue of the
      p150Glued component of the vertebrate dynactin complex.
AB  - p150Glued is the largest polypeptide in the dynactin complex, a protein
      heteromultimer that binds to and may mediate the microtubule-based motor
      cytoplasmic dynein. Cloning of a cDNA encoding p150Glued from rat revealed 31%
      amino acid sequence identity with the product of the Drosophila gene, Glued. A
      dominant Glued mutation results in neuronal disruption; null mutations are
      lethal. However, the Glued gene product has not been characterized. To determine
      whether the Glued polypeptide is functionally similar to vertebrate p150Glued, we
      characterized the Glued protein in the Drosophila S-2 cell line. Antibodies
      raised against Glued were used to demonstrate that this protein sediments
      exclusively at 20 S, and associates with microtubules in a salt- and ATP
      dependent manner. Immunoprecipitations from S-2 cytosol with the anti-Glued
      antibody resulted in the co-precipitation of subunits of both cytoplasmic dynein
      and the dynactin complex. An affinity column with covalently bound Glued protein
      retained cytoplasmic dynein from S-2 cytosol. Based on these observations, we
      conclude that Glued is a component of a dynactin complex in Drosophila and binds
      to cytoplasmic dynein, and therefore the mutant Glued phenotypes can be
      interpreted as resulting from a disruption in the function of the dynactin
      complex.

PMID- 8557645
TI  - Expression and functional role of syntaxin 1/HPC-1 in pancreatic beta cells.
      Syntaxin 1A, but not 1B, plays a negative role in regulatory insulin release
      pathway.
AB  - Syntaxin 1/HPC-1 is an integral membrane protein, which is thought to be
      implicated in the regulation of synaptic neurotransmitter release. We
      investigated syntaxin 1 expression in pancreatic beta cells and the functional
      role of syntaxin 1 in the insulin release mechanism. Expression of syntaxin 1A,
      but not 1B, was detected in mouse isolated islets by the reverse transcriptase
      polymerase chain reaction procedure. An immunoprecipitation study of
      metabolically labeled islets with an anti-rat syntaxin 1/HPC-1 antibody
      demonstrated syntaxin 1A protein with an apparent molecular mass of approximately
      35 kDa. Immunohistochemistry of the mouse pancreas demonstrated that syntaxin
      1/HPC-1 was present in the plasma membranes of the islets of Langerhans. In order
      to determine the functional role of syntaxin 1 in pancreatic beta-cells, rat
      syntaxin 1A or 1B was overexpressed in mouse beta TC3 cells using the transient
      transfection procedure. Transfection of beta TC3 cells with either syntaxin 1
      resulted in approximately 7-fold increases in their immunodetectable protein
      levels. Glucose-stimulated insulin release by syntaxin 1A-overexpressing cells
      was suppressed to about 50% of the level in control cells, whereas insulin
      release by syntaxin 1B-overexpressing and control cells did not differ. Next, we
      established stable beta TC3 cell lines that overexpressed syntaxin 1A and used
      them to evaluate the effect of syntaxin 1A on the regulatory insulin release
      pathway. Two insulin secretogogues, 4-beta-phorbol 12-myristate 13-acetate or
      forskolin, increased insulin release by untransfected beta TC3 cells markedly,
      but their effects were diminished in syntaxin 1A-overexpressing beta TC3 cells.
      Glucose-unstimulated insulin release and the proinsulin biosynthetic rate were
      not affected by syntaxin 1A overexpression, indicating a specific role of
      syntaxin 1A in the regulatory insulin release pathway. Finally, in vitro binding
      assays showed that syntaxin 1A binds to insulin secretory granules, indicating an
      inhibitory role of syntaxin 1A in insulin exocytosis via its interaction with
      vesicular proteins. These results demonstrate that syntaxin 1A is expressed in
      the islets of Langerhans and functions as a negative regulator in the regulatory
      insulin release pathway.

PMID- 8557646
TI  - Production and characterization of chimeric transferrins for the determination of
      the binding domains for bacterial transferrin receptors.
AB  - Pathogenic bacteria in the Neisseriaceae and Pasteurellaceae possess outer
      membrane proteins that specifically bind transferrin from the host as the first
      step in the iron acquisition process. As a logical progression from prior studies
      of the ligand-receptor interaction using biochemical approaches, we have
      initiated an approach involving the production of recombinant chimeric
      transferrins to further identify the regions of transferrin involved in receptor
      binding. In order to prepare bovine/human hybrids, the bovine transferrin gene
      was cloned, sequenced, and compared with the existing human transferrin gene
      sequence. After identification of potential splice sites, hybrid transferrin
      genes were constructed using the polymerase chain reaction-based approach of
      splicing by overlap extension. Five hybrid genes containing sequences from both
      bovine and human transferrin were constructed. Recombinant transferrins were
      produced in a baculovirus expression vector system and affinity-purified using
      concanavalin A-Sepharose. The recombinant proteins were analyzed for reactivity
      against polyclonal and monoclonal antibodies and assessed for binding to
      Neisseria meningitidis transferrin receptor proteins in solid-phase binding
      assays and affinity isolation experiments. These experiments enabled us to
      localize the regions of human transferrin predominantly involved in binding to
      the N. meningitidis receptor to amino acid residues 346-588. The construction of
      these chimeras provides unique tools for the investigation of transferrin binding
      to receptors from both human and bovine bacterial pathogens.

PMID- 8557647
TI  - Stimulus-dependent phosphorylation of MacMARCKS, a protein kinase C substrate, in
      nerve termini and PC12 cells.
AB  - MacMARCKS (also known as myristoylated alanine-rich C kinase substrate (MARCKS)
      related protein) is a member of the MARCKS family of protein kinase C substrates,
      which binds Ca2+/calmodulin in a phosphorylation-dependent manner.
      Immunoprecipitation demonstrated that MacMARCKS is present in both PC12 cells and
      in neurons. Upon depolarization of PC12 cells with 60 mM KCl, MacMARCKS
      phosphorylation increased 4-fold over basal levels in a Ca(2+)-dependent manner.
      By immunofluorescence microscopy, MacMARCKS was colocalized in PC12 cells to
      neurite tips with the synaptic vesicle membrane protein synaptophysin and to
      vesicles in the perinuclear region. Subcellular fractionation demonstrated that
      MacMARCKS associates tightly with membranes in PC12 cells. In Percoll-purified
      rat cerebrocortical synaptosomes, depolarization with 60 mM KCl in the presence
      of exogenous Ca2+ transiently increased MacMARCKS phosphorylation, whereas
      phorbol ester promoted a sustained increase in MacMARCKS phosphorylation.
      Subcellular fractionation of rat brain indicated that MacMARCKS was present in
      both soluble and particulate fractions; particulate MacMARCKS was associated with
      both small vesicles and highly purified synaptic vesicles. These results are
      consistent with a role for MacMARCKS in integrating Ca(2+)-calmodulin and protein
      kinase C-dependent signals in the regulation of neurosecretion.

PMID- 8557648
TI  - Prostaglandin F2 alpha stimulates hypertrophic growth of cultured neonatal rat
      ventricular myocytes.
AB  - Prostaglandin F2 alpha (PGF2 alpha) stimulates protein synthesis of skeletal and
      smooth muscle cells in culture and is elevated in the heart during compensatory
      growth. We hypothesized that PGF2 alpha stimulates hypertrophic growth of
      neonatal rat cardiac myocytes. Prostaglandin F2 alpha increased [3H]phenylalanine
      incorporation by cultured ventricular myocytes in a dose-dependent manner (EC50 =
      11 nM), suggesting action through a PGF-specific receptor. Semiquantitative
      reverse transcriptase polymerase chain reaction revealed that PGF receptor mRNA
      is expressed in ventricular myocytes > A7R5 vascular smooth muscle cells >>
      cardiac fibroblast-like cells. The protein content of cardiomyocyte cultures was
      increased by 10 nM PGF2 alpha and 11 beta-PGF2 alpha but was unchanged by 10 nM
      PGD2, PGE2, PGF1 alpha, carbaprostacyclin, U-46619, or 12- or 15
      hydroxyeicosatrienoic acid. Stimulation of myofibrillar gene expression by PGF2
      alpha was demonstrated by Northern and Western blot analysis for myosin light
      chain-2 (MLC-2) and by transient transfection experiments with MLC-2 luciferase
      expression plasmids. In addition, myofibrillogenesis was increased by PGF2 alpha
      as assessed by immunocytochemical staining with MLC-2 antisera. Prostaglandin F2
      alpha did not affect myocyte proliferation or [3H]thymidine incorporation, thus
      myocyte growth occurred by hypertrophy. Proliferative and hypertrophic growth of
      cardiac fibroblast-like cells were unaffected by PGF2 alpha. We conclude that
      PFG2 alpha stimulates hypertrophic growth of neonatal rat ventricular myocytes in
      culture and speculate that PGF2 alpha plays a role in myocardial adaptation to
      chronic hypertrophic stimuli, recovery from injury, and cardiac ontogeny.

PMID- 8557649
TI  - Variable nuclear cytoplasmic distribution of the 11.5-kDa zinc-binding protein
      (parathymosin-alpha) and identification of a bipartite nuclear localization
      signal.
AB  - The 11.5-kDa zinc-binding protein (ZnBP, parathymosin-alpha), a potent
      inactivator of 1-phosphofructokinase, is found only in the cytoplasm of most
      tissues despite the presence of the putative nuclear localization signal PKRQKT.
      Recent reports on nuclear uptake of ZnBP could not exclude the participation of
      unspecific diffusion. We show here that wild-type ZnBP overexpressed in COS cells
      accumulates exclusively in the nucleus but that ZnBP with a mutated or deleted
      PKRQKT motif appears both in the nucleus and in the cytoplasm. In contrast,
      fusion proteins between ZnBP and parts of the endoplasmic reticulum protein
      calreticulin required the intact PKRQKT motif for nuclear import. The motif RKR,
      located nine amino acids upstream of the PKRQKT motif, is also involved in the
      active nuclear import of ZnBP. In contrast to rat hepatocytes and kidney cells in
      situ, which have ZnBP almost exclusively in the cytosol, we find ZnBP in Reuber
      H35 hepatoma cells and normal rat kidney cells only in the nuclei. Freshly
      isolated rat hepatocytes translocate their ZnBP to the nucleus in < 24 h during
      standard cell culture conditions.

PMID- 8557650
TI  - Prosomatostatin processing in permeabilized cells. Calcium is required for
      prohormone cleavage but not formation of nascent secretory vesicles.
AB  - Our laboratory has been using a permeabilized cell system derived from rat
      anterior pituitary GH3 cells expressing prosomatostatin (pro-SRIF) to study
      prohormone processing and nascent secretory vesicle formation in vitro. Because
      calcium is necessary for prohormone processing enzyme activity, secretory granule
      fusion with the plasma membrane, and possibly sorting to the regulated pathway,
      we treated permeabilized cells with the calcium ionophore A23187 to determine the
      role of calcium in pro-SRIF cleavage and nascent vesicle formation from the trans
      Golgi network (TGN). Here we demonstrate that pro-SRIF cleavage was markedly
      inhibited when lumenal free calcium was chelated with EGTA in the presence of
      A23187. Surprisingly, submillimolar free calcium (approximately 15 microM) was
      sufficient to maintain prohormone cleavage efficiency, a value far lower than
      that estimated for total calcium levels in the TGN and secretory granules.
      Experiments using both A23187 and the protonophore CCCP revealed that free
      calcium is absolutely required for efficient pro-SRIF cleavage, even at the
      optimal pH of 6.1. Secretory vesicle formation by contrast was not inhibited by
      calcium chelation but rather by millimolar extralumenal free calcium. Together,
      these observations demonstrate that pro-SRIF processing and budding of nascent
      secretory vesicles from the TGN can be uncoupled and therefore have distinct
      biochemical requirements. Interestingly, our data using intact GH3 cells
      demonstrate that basal secretion of SRIF-related material is largely calcium
      dependent and therefore cannot be equated with constitutive pathway secretion.
      These results underscore the importance of determining calcium requirements
      before assigning a secretion event to either the constitutive or regulated
      secretory pathway.

PMID- 8557651
TI  - Overexpression of parathyroid hormone-related protein in the pancreatic islets of
      transgenic mice causes islet hyperplasia, hyperinsulinemia, and hypoglycemia.
AB  - Parathyroid hormone-related protein (PTHrP) is produced by the pancreatic islet.
      It also has receptors on islet cells, suggesting that it may serve a paracrine or
      autocrine role within the islet. We have developed transgenic mice, which
      overexpress PTHrP in the islet through the use of the rat insulin II promoter
      (RIP). Glucose homeostasis in these mice is markedly abnormal; RIP-PTHrP mice are
      hypoglycemic in the postprandial and fasting states and display inappropriate
      hyperinsulinemia. At the end of a 24-hour fast, blood glucose values are 49 mg/dl
      in RIP-PTHrP mice, as compared to 77 mg/dl in normal littermates; insulin
      concentrations at this time are 6.3 and 3.9 ng/ml, respectively. Islet perifusion
      studies failed to demonstrate abnormalities in insulin secretion. In contrast,
      quantitative islet histomorphometry demonstrates that the total islet number and
      total islet mass are 2-fold higher in RIP-PTHrP mice than in their normal
      littermates. PTHrP very likely plays a normal physiologic role within the
      pancreatic islet. This role is most likely paracrine or autocrine. PTHrP appears
      to regulate insulin secretion either directly or indirectly, through
      developmental or growth effects on islet mass. PTHrP may have a role as an agent
      that enhances islet mass and/or enhances insulin secretion.

PMID- 8557652
TI  - Two types of anti-progestins have distinct effects on site-specific
      phosphorylation of human progesterone receptor.
AB  - Human progesterone receptor (PR) is phosphorylated on multiple serine residues;
      three sites (Ser102, Ser294, and Ser345) are inducible by hormone agonist, while
      at least six others are basally phosphorylated and exhibit a general increase in
      response to hormone. In this study we have used high performance liquid
      chromatography phosphopeptide mapping and manual peptide sequencing to
      investigate how two different progestin antagonists, RU486 and ZK98299, affect
      site-specific phosphorylation of PR isolated from T47D breast cancer cells. As
      compared to the progestin agonist R5020, RU486 stimulated a similar increase in
      overall incorporation of [32P]phosphate per PR molecule (2.5-2.6-fold for PR-A
      and 2.1-fold for PR-B), and at the site-specific level, RU486 stimulated both the
      basal and inducible sites to the same extent as R5020. In contrast, ZK98299
      produced only a minimal increase in overall phosphorylation (1.2-fold for PR-A
      and 1.1-fold for PR-B) which was due to a reduced stimulation of the basal sites
      and failure to induce any of the three hormone-dependent sites. No inappropriate
      phosphorylation sites were detected in response to either RU486 or ZK98299. In
      cotreatment studies, ZK98299 blocked the increase in overall phosphorylation of
      PR induced by R5020, demonstrating that the failure of this antagonist to
      stimulate specific phosphorylation sites is not due to an inefficient interaction
      with PR in the intact cell. These results indicate that the biological effects of
      RU486 are not mediated by an alternation in the phosphorylation state of PR,
      whereas failure to promote phosphorylation of certain sites may contribute to the
      antagonist action of ZK98299. Additionally these results support the concept of
      two mechanistic classes of anti-progestins that affect PR differently in vivo.

PMID- 8557653
TI  - Identification of an essential cis-element near the transcription start site for
      transcriptional activation of the proliferating cell nuclear antigen gene.
AB  - Interleukin 2 (IL-2) stimulates T lymphocyte proliferation and induces the
      expression of proliferating cell nuclear antigen (PCNA), a processivity factor
      for DNA polymerase delta. Previously, deletion analysis suggested cis-element(s)
      in the proximal region of the PCNA promoter (-40 to +143) are required for IL-2
      induction in cloned T lymphocytes. The sequence 5'-TTGCGGGC-3' located at +10 to
      +17 is similar to the E2F consensus binding site and is required for optimal PCNA
      promoter activity. In IL-2-stimulated T cells, nuclear proteins are induced to
      bind to this sequence as demonstrated using electrophoretic mobility shift assay
      (EMSA), competition EMSA, and methylation interference analysis. A 180-kDa
      polypeptide was detected by UV cross-linking to bind specifically to the PCNA E2F
      like sequence. Our data indicate that the protein bound to the PCNA E2F-like site
      is not one of the transcription factor E2F proteins. Our results demonstrate that
      the E2F-like sequence and the protein(s) binding to it are required for optimal
      PCNA promoter activity and IL-2 induction of PCNA expression.

PMID- 8557654
TI  - Oligomerization of the phosphatase CheZ upon interaction with the phosphorylated
      form of CheY. The signal protein of bacterial chemotaxis.
AB  - Earlier studies have suggested that CheZ, the phosphatase of the signaling
      protein CheY in bacterial chemotaxis, may be in an oligomeric state both when
      bound to phosphorylated CheY (CheY approximately P) (Blat, Y., and Eisenbach, M.
      (1994) Biochemistry 33, 902-906) or free (Stock, A., and Stock, J. B. (1987) J.
      Bacteriol. 169, 3301-3311). The purpose of the current study was to determine the
      oligomeric state of free CheZ and to investigate whether it changes upon binding
      to CheY approximately P. By using either one of two different sets of cross
      linking agents, free CheZ was found to be a dimer. The formation of the dimer was
      specific, as it was prevented by SDS which does not interfere with cross-linking
      mediated by random collisions. The dimeric form of CheZ was confirmed by
      sedimentation analysis, a cross-linking-free technique. In the presence of CheY
      approximately P (but not in the presence of non-phosphorylated CheY), a high
      molecular size cross-linked complex (90-200 kDa) was formed, in which the
      CheZ:CheY ratio was 2:1. The size of the oligomeric complex was estimated by
      fluorescence depolarization to be 4-5-fold larger than the dimer, suggesting that
      its size is in the order of 200 kDa. These results indicate that CheZ
      oligomerizes upon interaction with CheY approximately P. This phosphorylation
      dependent oligomerization may be a mechanism for regulating CheZ activity.

PMID- 8557655
TI  - Mutants with defective phosphatase activity show no phosphorylation-dependent
      oligomerization of CheZ. The phosphatase of bacterial chemotaxis.
AB  - CheZ is the phosphatase of CheY, the response regulator in bacterial chemotaxis.
      The mechanism by which the activity of CheZ is regulated is not known. We used
      cheZ mutants of Salmonella typhimurium, which had been isolated by Sockett et al.
      (Sockett, H., Yamaguchi, S., Kihara, M., Irikura, V. M., and Macnab, R. M. (1992)
      J. Bacteriol. 174, 793-806), for cloning the mutant cheZ genes, overexpressing
      and purifying their products. We then measured the phosphatase activity, binding
      to CheY and to phosphorylated CheY (CheY approximately P), and CheY approximately
      P dependent oligomerization of the mutant CheZ proteins. While all the mutant
      proteins were defective in their phosphatase activity, they bound to CheY and
      CheY approximately P as well as wild-type CheZ. However, unlike wild-type CheZ,
      all the four mutant proteins failed to oligomerize upon interaction with CheY
      approximately P. On the basis of these and earlier results it is suggested that
      (i) oligomerization is required for the phosphatase activity of CheZ, (ii) the
      region defined by residues 141-145 plays an important role in mediating CheZ
      oligomerization and CheY approximately P dephosphorylation but is not necessary
      for the binding to CheY approximately P, (iii) the oligomerization and hence the
      phosphatase activity are regulated by the level of CheY approximately P, and (iv)
      this regulation plays a role in the adaptation to chemotactic stimuli.

PMID- 8557656
TI  - Regulation of sucrase-isomaltase gene expression in human intestinal epithelial
      cells by inflammatory cytokines.
AB  - Using metabolic labeling techniques in human intestinal epithelial cell lines in
      tissue culture and in situ hybridization techniques in normal and inflamed
      (Crohn's) intestine, recent studies have shown that there is synthesis of acute
      phase proteins in enterocytes. Moreover, these studies have shown that acute
      phase protein biosynthesis in enterocytes is regulated by inflammatory cytokines
      in a manner characteristic of the physiologic acute phase response. In the course
      of these studies it was noticed that one inflammatory cytokine, interleukin-6 (IL
      6), mediated selective down-regulation of the enterocyte-specific,
      differentiation-dependent integral membrane protein sucrase-isomaltase (SI) in
      the Caco2 intestinal epithelial cell line. In the current study we examined the
      effect of several other inflammatory cytokines interleukin-1 (IL-1 beta), tumor
      necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma) on synthesis
      of SI in Caco2 cells, examined the possibility that inflammatory cytokines affect
      the synthesis of other enterocyte integral membrane proteins using lactase as a
      prototype, and examined the possibility that SI gene expression was down
      regulated in villous enterocytes in vivo during the local inflammatory response
      of Crohn's disease. The results show that IL-6 and IFN gamma each mediate a
      decrease and TNF alpha mediates an increase in synthesis of SI in Caco2 cells.
      The magnitude of down-regulation by IL-6 and IFN gamma is significantly greater
      than the up-regulation by TNF alpha. IL-1 beta has no effect on synthesis of SI.
      Synthesis of lactase is not affected by any of the cytokines. There is a marked
      specific decrease in SI gene expression in villous enterocytes in acutely
      inflamed Crohn's ileum as compared to adjacent uninflamed ileum and normal ileum.
      Taken together, these data show that inflammatory cytokines have specific and
      selective effects on the expression of the brush border hydrolase SI in tissue
      culture and in vivo and provide evidence for a previously unrecognized mechanism
      for disaccharidase deficiency in intestinal inflammation.

PMID- 8557657
TI  - Molecular dissection of effector cell protease receptor-1 recognition of factor
      Xa. Assignment of critical residues involved in antibody reactivity and ligand
      binding.
AB  - Receptor-mediated assembly of blood proteases on vascular cells maintains the
      hemostatic balance and initiates intracellular signal transduction. Effector cell
      protease receptor-1 (EPR-1) is an approximately 62-kDa vascular cell membrane
      receptor for the clotting protease factor Xa, participating in thrombin formation
      and lymphocyte activation. Here, recombinant EPR-1 fragments were engineered in
      the frame of intercellular adhesion molecule-1, transfected in mammalian cells,
      and analyzed for antibody recognition and ligand binding. Chimeric transfectants
      containing the EPR-1 sequence Met1-Arg60 bound the immunosuppressive anti-EPR-1
      monoclonal antibody (mAb) 2E1. In contrast, transfected cells expressing the EPR
      1 sequence Pro120-Ala154 were recognized by the functionally inhibitory anti-EPR
      1 mAbs 9D4 and B6, bound 125I-factor Xa in a reaction quantitatively
      indistinguishable from that of wild-type EPR-1 transfectants, and promoted factor
      Xa concentration-dependent prothrombin activation in the absence of exogenous
      factor V/Va. Chimeric transfectants expressing the COOH terminus end of the EPR-1
      extracellular domain (Ala157-Glu221) did not bind anti-EPR-1 mAbs and did not
      associate with factor Xa. Mutagenesis of Asn131 or Lys133 in the EPR-1 ligand
      recognition domain abolished factor Xa binding by 80 +/- 5.5 and 96 +/- 4%,
      respectively, while mutation of Lys126, Gly128, Asn129, and Asn134 was without
      effect. A synthetic peptide duplicating the EPR-1 sequence S123PGKPGNQNSKNEPP137
      dose dependently inhibited factor V/Va-independent thrombin generation of resting
      endothelium (IC50 approximately 1 microM), while the adjacent EPR-1 sequence
      P136PKK-RERERSSHCYP150 was ineffective. These findings demonstrate that EPR-1
      contains two spatially distinct functional domains implicated in lymphocyte
      activation (Met1-Arg60) or factor Xa binding and prothrombin activation (Pro120
      Ala154). These interacting sequences may provide a novel potential target for
      inhibition of factor Xa-dependent vascular cell responses.

PMID- 8557658
TI  - Vascular endothelial growth factor, a potent and selective angiogenic agent.

PMID- 8557659
TI  - Identification of AF-6 and canoe as putative targets for Ras.
AB  - Ras (Ha-Ras, Ki-Ras, N-Ras) is implicated in the regulation of various cell
      functions such as gene expression and cell proliferation downstream from specific
      extracellular signals. Here, we partially purified a Ras-interacting protein with
      molecular mass of about 180 kDa (p180) from bovine brain membrane extract by
      glutathione S-transferase (GST)-Ha-Ras affinity column chromatography. This
      protein bound to the GTP gamma S (guanosine 5'-(3-O-thio)triphosphate, a
      nonhydrolyzable GTP analog).GST-Ha-Ras affinity column but not to those
      containing GDP.GST-Ha-Ras or GTP gamma S.GST-Ha-Ras with a mutation in the
      effector domain (Ha-RasA38). The amino acid sequences of the peptides derived
      from p180 were almost identical to those of human AF-6 that is identified as the
      fusion partner of the ALL-1 protein. The ALL-1/AF-6 chimeric protein is the
      critical product of the t (6:11) abnormality associated with some human leukemia.
      AF-6 has a GLGF/Dlg homology repeat (DHR) motif and shows a high degree of
      sequence similarity with Drosophila Canoe, which is assumed to function
      downstream from Notch in a common developmental pathway. The recombinant N
      terminal domain of AF-6 and Canoe specifically interacted with GTP gamma S.GST-Ha
      Ras. The known Ras target c-Raf-1 inhibited the interaction of AF-6 with GTP
      gamma S.GST-Ha-Ras. These results indicate that AF-6 and Canoe are putative
      targets for Ras.

PMID- 8557660
TI  - Mammalian AMP-activated protein kinase subfamily.
AB  - The mammalian 5'-AMP-activated protein kinase (AMPK) is related to a growing
      family of protein kinases in yeast and plants that are regulated by nutritional
      stress. We find the most prominent expressed form of the hepatic AMPK catalytic
      subunit (alpha 1) is distinct from the previously cloned kinase subunit (alpha
      2). The alpha 1 (548 residues) and alpha 2 (552 residues) isoforms have 90% amino
      acid sequence identity within the catalytic core but only 61% identity elsewhere.
      The tissue distribution of the AMPK activity most closely parallels the low
      abundance 6-kilobase alpha 1 mRNA distribution and the alpha 1 immunoreactivity
      rather than alpha 2, with substantial amounts in kidney, liver, lung, heart, and
      brain. Both alpha 1 and alpha 2 isoforms are stimulated by AMP and contain
      noncatalytic beta and gamma subunits. The liver alpha 1 isoform accounts for
      approximately 94% of the enzyme activity measured using the SAMS peptide
      substrate. The tissue distribution of the alpha 2 immunoreactivity parallels the
      alpha 2 8.5-kilobase mRNA and is most prominent in skeletal muscle, heart, and
      liver. Isoforms of the beta and gamma subunits present in the human genome
      sequence reveal that the AMPK consists of a family of isoenzymes.

PMID- 8557661
TI  - Tumor necrosis factor promotes phosphorylation and binding of insulin receptor
      substrate 1 to phosphatidylinositol 3-kinase in 3T3-L1 adipocytes.
AB  - Chronic incubation of 3T3-L1 adipocytes with tumor necrosis factor (TNF) induces
      a state of insulin resistance characterized by a diminished ability of insulin to
      induce phosphorylation of the beta subunit of its own receptor and insulin
      receptor substrate 1 (IRS-1). When adipocytes are briefly pretreated with TNF and
      then stimulated with insulin, tyrosine phosphorylation of IRS-1 increases above
      the level induced by insulin alone. By itself, TNF induces the time-dependent
      tyrosine phosphorylation of proteins in 3T3-L1 adipocytes. Among these is IRS-1,
      a docking protein with tyrosine phosphorylation sites that bind cytoplasmic
      signaling molecules that contain Src homology 2 (SH2) domains. TNF stimulation of
      3T3-L1 adipocytes also promotes the association of the p85 regulatory subunit of
      phosphatidylinositol 3-kinase (PI 3-kinase) with IRS-1 and also its tyrosine
      phosphorylation. In murine 3T3-L1 adipocytes, IRS-1 and PI 3-kinase
      phosphorylation and the association of these proteins are promoted by murine TNF,
      which interacts with the type 1 and type 2 TNF receptors. Human TNF, which binds
      to the murine type 1 TNF receptor selectively, also promotes IRS-1
      phosphorylation and binding of IRS-1 to PI 3-kinase. This is the first
      demonstration that a member of the TNF/nerve growth factor receptor superfamily
      can use an IRS-1 signaling system as a component of its cellular response and
      provides a mechanism through which TNF receptors may engage downstream elements
      in signaling pathways.

PMID- 8557662
TI  - Signal transduction pathway of interleukin-4 and interleukin-13 in human B cells
      derived from X-linked severe combined immunodeficiency patients.
AB  - Interleukin-4 (IL-4) and IL-13 are functionally similar cytokines. The functional
      IL-4 receptor (IL-4R) consists of the IL-4R alpha chain (IL-4R alpha) and the IL
      2R gamma chain (gamma c), which is shared by the IL-2, IL-7, IL-9, and IL-15
      receptors. The functional IL-13R is thought to involve the IL-4R alpha but not
      gamma c. In this study, we have analyzed activation of members of the Janus
      tyrosine kinase (Jak) family and signal transducers and activators of
      transcription (STAT) 6 induced by IL-4 and IL-13 in Epstein-Barr virus
      transformed B cells derived from two patients of X-linked severe combined
      immunodeficiency, who have mutations of the gamma c gene in the extracellular and
      intracellular domains. In these B cells, IL-4 failed to induce tyrosine
      phosphorylation of Jak3 and activation of STAT6, or activation of these molecules
      was significantly decreased compared with Epstein-Barr virus-transformed normal B
      cells. In contrast, IL-13 activated STAT6 in these cells as well as normal B
      cells. However, Jak3 was not activated by IL-13, even in normal B cells. These
      results clearly indicated that gamma c is essential for activation of Jak3 and
      STAT6 in the signal transduction pathway of IL-4 in human B cells and that IL-13
      does not utilize gamma c but activates STAT6 through an alternative pathway,
      which is not impaired in B cells of X-linked severe combined immunodeficiency
      patients.

PMID- 8557663
TI  - Internal initiation of translation directed by the 5'-untranslated region of the
      mRNA for eIF4G, a factor involved in the picornavirus-induced switch from cap
      dependent to internal initiation.
AB  - The eIF4 group initiation factors carry out recognition of the mRNA cap,
      unwinding of mRNA secondary structure, and binding of mRNA to the 43 S
      preinitiation complex. Infection by picornaviruses results in proteolytic
      cleavage of one of these factors, eIF4G, an event that severely restricts cap
      dependent translation but permits cap-independent initiation to proceed from
      internal ribosome entry sequences in picornaviral RNAs. The 5'-untranslated
      region (5'-UTR) of eIF4G mRNA resembles such picornaviral sequences in being
      unusually long and containing multiple open reading frames and a polypyrimidine
      tract. When inserted upstream of a luciferase reporter gene, this 5'-UTR served
      as a translational enhancer in four different cell lines. Mutation of all four
      upstream ATG codons to AAG did not alter the translational enhancement. The
      presence of the eIF4G 5'-UTR between an RNA hairpin and the luciferase cistron
      stimulated expression 119-fold. Similarly, the presence of the 5'-UTR between the
      two cistrons of a bicistronic mRNA stimulated expression of the downstream
      cistron 42-fold. These results indicate that the eIF4G 5'-UTR directs internal
      initiation. The ability to continue synthesis of eIF4G when the cell is unable to
      carry out normal cap-dependent translation may represent an autoregulatory
      mechanism or be part of the cellular response to stresses that interrupt cap
      dependent translation.

PMID- 8557664
TI  - Traveling NADH and proton waves during oscillatory glycolysis in vitro.
AB  - Propagation and mutual annihilation of circular and spiral NADH and proton waves
      were detected by spatially resolved spectrophotometry and fluorescent proton
      indicators in a biological in vitro system: an organelle-free yeast extract.
      Spontaneous wave generation during glycolytic sugar degradation is established
      after an induction period of about 1 h. Controlled wave initiation could be
      performed by local injection of the strong activator of phosphofructokinase,
      fructose 2,6-bisphosphate. A crucial role for wave initiation and control of
      pattern dynamics is attributed to the key enzyme of glycolysis, the
      allosterically regulated phosphofructokinase. An overall increase in the
      concentration of its positive effector AMP leads to the formation of rotating
      spirals. The dynamics of the observed wave patterns resemble that of self
      organized calcium waves as recently found in frog eggs and heart cells.

PMID- 8557665
TI  - Persistent activation of c-Jun N-terminal kinase 1 (JNK1) in gamma radiation
      induced apoptosis.
AB  - The c-Jun N-terminal kinases (JNK) are activated by various stimuli, including UV
      light, interleukin-1, tumor necrosis factor-alpha (TNF-alpha), and CD28
      costimulation. Induction of JNK by TNF-alpha, a strong apoptosis inducer, implies
      a possible role of JNK in the regulation of programmed cell death. Present
      studies show that lethal doses of gamma radiation (GR) induced JNK activities at
      the early phase of apoptosis in Jurkat T-cells. We demonstrate that JNK1 was
      activated by either the T-cell activation signals, anti-CD28 monoclonal antibody
      plus phorbol 12-myristate 13-acetate (PMA), or the apoptosis-inducing treatment,
      GR; however, the induction patterns were different. In contrast to the rapid and
      transient JNK1 activation caused by CD28 signaling plus PMA, GR induced a delayed
      and persistent JNK1 activation. This implies a distinct regulatory mechanism and
      specific function of JNK1 in irradiated cells. The nuclear and cytosolic JNK1
      activities were simultaneously increased in the irradiated cells without an
      evident change in the protein levels. The abilities of GR to induce JNK1
      activation and DNA fragmentation were correlated. Peripheral blood lymphocytes
      were more sensitive to GR than Jurkat cells in JNK1 induction. The responsiveness
      of JNK1 to GR suggests the involvement of JNK1 in the initiation of the apoptosis
      process.

PMID- 8557666
TI  - Glycerol reverses the misfolding phenotype of the most common cystic fibrosis
      mutation.
AB  - The common delta F508 mutation in the cystic fibrosis transmembrane conductance
      regulator (CFTR) interferes with the biosynthetic folding of nascent CFTR
      polypeptides, leading to their retention and rapid degradation in an
      intracellular compartment proximal to the Golgi apparatus. Neither the pathway by
      which wild-type CFTR folds nor the mechanism by which the Phe508 deletion
      interferes with this process is well understood. We have investigated the effect
      of glycerol, a polyhydric alcohol known to stabilize protein conformation, on the
      folding of CFTR and delta F508 in vivo. Incubation of transient and stable delta
      F508 transfectants with 10% glycerol induced a significant accumulation of delta
      F508 protein bearing complex N-linked oligosaccharides, indicative of their
      transit to a compartment distal to the endoplasmic reticulum (ER). This
      accumulation was accompanied by an increase in mean whole cell cAMP activated
      chloride conductance, suggesting that the glycerol-rescued delta F508
      polypeptides form functional plasma membrane CFTR channels. These effects were
      dose- and time-dependent and fully reversible. Glycerol treatment also stabilized
      immature (core-glycosylated) delta F508 and CFTR molecules that are normally
      degraded rapidly. These effects of glycerol were not due to a general disruption
      of ER quality control processes but appeared to correlate with the degree of
      temperature sensitivity of specific CFTR mutations. These data suggest a model in
      which glycerol serves to stabilize an otherwise unstable intermediate in CFTR
      biosynthesis, maintaining it in a conformation that is competent for folding and
      subsequent release from the ER quality control apparatus.

PMID- 8557667
TI  - Induction of mitogen-activated protein kinase phosphatase 1 by the stress
      activated protein kinase signaling pathway but not by extracellular signal
      regulated kinase in fibroblasts.
AB  - The intracellular mechanisms involved in the activation of extracellular signal
      regulated kinase (ERK) are relatively well understood. However, the intracellular
      signaling pathways which regulate the termination of ERK activity remain to be
      elucidated. Mitogen-activated protein kinase phosphatase 1 (MKP-1) has been shown
      to dephosphorylate and inactivate ERK in vitro and in vivo. In the present study,
      we show in NIH3T3 fibroblasts that activation of the stress-activated protein
      kinase (SAPK) pathway by either specific extracellular stress stimuli or via
      induction of MEKK, an upstream kinase of SAPK, results in MKP-1 gene expression.
      In contrast, selective stimulation of the ERK pathway by 12-O
      tetradecanoylphorbol-13-acetate or following expression of constitutively active
      MEK, the upstream dual specificity kinase of ERK did not induce the transcription
      of MKP-1. Hence, these findings demonstrate the existence of cross-talk between
      the ERK and SAPK signaling cascades since activation of SAPK induced the
      expression of MKP-1 that can inactivate ERK. This mechanism may modulate the
      cellular response to stimuli which employ the SAPK signal transduction pathway.

PMID- 8557668
TI  - Subunits of yeast RNA polymerase II transcription factor TFIIH encoded by the
      CCL1 gene.
AB  - Both 45- and 47-kDa subunits of TFIIK, a subcomplex of RNA polymerase II general
      transcription factor TFIIH, are encoded by the yeast cyclin gene CCL1. In all
      likelihood, these two subunits individually form cyclin-dependent kinase/cyclin
      dimers with Kin28 protein, a key enzyme in phosphorylation of the C-terminal
      domain of RNA polymerase II concomitant with transcription.

PMID- 8557669
TI  - Initial binding of the elongation factor Tu.GTP.aminoacyl-tRNA complex preceding
      codon recognition on the ribosome.
AB  - The first step in the sequence of interactions between the ribosome and the
      complex of elongation factor Tu (EF-Tu), GTP, and aminoacyl-tRNA, which
      eventually leads to A site-bound aminoacyl-tRNA, is the codon-independent
      formation of an initial complex. We have characterized the initial binding and
      the resulting complex by time-resolved (stopped-flow) and steady-state
      fluorescence measurements using several fluorescent tRNA derivatives. The complex
      is labile, with rate constants of 6 x 10(7) M-1 s-1 and 24 s-1 (20 degrees C, 10
      mM Mg2+) for binding and dissociation, respectively. Both thermodynamic and
      activation parameters of initial binding were determined, and five Mg2+ ions were
      estimated to participate in the interaction. While a cognate ternary complex
      proceeds form initial binding through codon recognition to rapid GTP hydrolysis,
      the rate constant of GTP hydrolysis in the non-cognate complex is 4 orders of
      magnitude lower, despite the rapid formation of the initial complex in both
      cases. Hence, the ribosome-induced GTP hydrolysis by EF-Tu is strongly affected
      by the presence of the tRNA. This suggests that codon-anticodon recognition,
      which takes place after the formation of the initial binding complex, provides a
      specific signal that triggers fast GTP hydrolysis by EF-Tu on the ribosome.

PMID- 8557670
TI  - Lipoyl domain-based mechanism for the integrated feedback control of the pyruvate
      dehydrogenase complex by enhancement of pyruvate dehydrogenase kinase activity.
AB  - To conserve carbohydrate reserves, the reaction of the pyruvate dehydrogenase
      complex (PDC) must be down-regulated when the citric acid cycle is provided
      sufficient acetyl-CoA. PDC activity is reduced primarily through increased
      phosphorylation of its pyruvate dehydrogenase (E1) component due to E1 kinase
      activity being markedly enhanced by elevated intramitochondrial NADH:NAD+ and
      acetyl-CoA:CoA ratios. A mechanism is evaluated in which enhanced kinase activity
      is facilitated by the build-up of the reduced and acetylated forms of the lipoyl
      moieties of the dihydrolipoyl acetyltransferase (E2) component through using NADH
      and acetyl-CoA in the reverse of the downstream reactions of the complex. Using a
      peptide substrate, kinase activity was stimulated by these products, ruling out
      the possibility kinase activity is increased due to changes in the reaction state
      of its substrate, E1 (thiamin pyrophosphate). Each E2 subunit contains two lipoyl
      domains, an NH2-terminal (L1) and the inward lipoyl domain (L2), which were
      individually produced in fully lipoylated forms by recombinant techniques.
      Although reduction and acetylation of the L1 domain or free lipoamide increased
      kinase activity, those modifications of the lipoate of the kinase-binding L2
      domain gave much greater enhancements of kinase activity. The large stimulation
      of the kinase generated by acetyl-CoA only occurred upon addition of the
      transacetylase-catalyzing (lipoyl domain-free) inner core portion of E2 plus a
      reduced lipoate source, affirming that acetylation of this prosthetic group is an
      essential mechanistic step for acetyl-CoA enhancing kinase activity. Similarly,
      the lesser stimulation of kinase activity by just NADH required a lipoate source,
      supporting the need for lipoate reduction by E3 catalysis. Complete enzymatic
      delipoylation of PDC, the E2-kinase subcomplex, or recombinant L2 abolished the
      stimulatory effects of NADH and acetyl-CoA. Retention of a small portion of PDC
      lipoates lowered kinase activity but allowed stimulation of this residual kinase
      activity by these products. Reintroduction of lipoyl moieties, using lipoyl
      protein ligase, restored the capacity of the E2 core to support high kinase
      activity along with stimulation of that activity up to 3-fold by NADH and acetyl
      CoA. As suggested by those results, the enhancement of kinase activity is very
      responsive to reductive acetylation with a half-maximal stimulation achieved with
      approximately 20% of free L2 acetylated and, from an analysis of previous
      results, with acetylation of only 3-6 of the 60 L2 domains in intact PDC. Based
      on these findings, we suggest that kinase stimulation results from modification
      of the lipoate of an L2 domain that becomes specifically engaged in binding the
      kinase. In conclusion, kinase activity is attenuated through a substantial range
      in response to modest changes in the proportion of oxidized, reduced, and
      acetylated lipoyl moieties of the L2 domain of E2 produced by fluctuations in the
      NADH:NAD+ and acetyl-CoA:CoA ratios as translated by the rapid and reversible E3
      and E2 reactions.

PMID- 8557671
TI  - Structural analysis of monosaccharide recognition by rat liver mannose-binding
      protein.
AB  - The structural basis of carbohydrate recognition by rat liver mannose-binding
      protein (MBP-C) has been explored by determining the three-dimensional structure
      of the C-type carbohydrate-recognition domain (CRD) of MBP-C using x-ray
      crystallography. The structure was solved by molecular replacement using rat
      serum mannose-binding protein (MBP-A) as a search model and was refined to
      maximum Bragg spacings of 1.7 A. Despite their almost identical folds, the
      dimeric structures formed by the two MBP CRDs differ dramatically. Complexes of
      MBP-C with methyl glycosides of mannose, N-acetylglucosamine, and fucose were
      prepared by soaking MBP-C crystals in solutions containing these sugars.
      Surprisingly, the pyranose ring of mannose is rotated 180 degrees relative to the
      orientation observed previously in MBP-A, but the local interactions between
      sugar and protein are preserved. For each of the bound sugars, vicinal,
      equatorial hydroxyl groups equivalent to the 3- and 4-OH groups of mannose
      directly coordinate Ca2+ and form hydrogen bonds with residues also serving as
      Ca2+ ligands. Few interactions are observed between other parts of the sugar and
      the protein. A complex formed between free galactose and MBP-C reveals a similar
      mode of binding, with the anomeric hydroxyl group serving as one of the Ca2+
      ligands. A second binding site for mannose has also been observed in one of two
      copies in the asymmetric unit at a sugar concentration of 1.3 M. These structures
      explain how MBPs recognize a wide range of monosaccharides and suggest how fine
      specificity differences between MBP-A and MBP-C may be achieved.

PMID- 8557672
TI  - A doubly cross-linked human hemoglobin. Effects of cross-links between different
      subunits.
AB  - Human deoxyhemoglobin cross-linked with trimesyl tris(3,5-dibromosalicylate)
      produces the previously reported cross-linked hemoglobin in which the epsilon
      amino groups of the two beta chain 82 lysyl residues are joined by a trimesyl
      bridge. Further specific modification of this protein directed to the alpha
      subunits with bis(3,5-dibromosalicyl)fumarate gives a doubly cross-linked
      material in which the epsilon-amino groups of the two alpha chain 99 lysyl
      residues are now joined by a fumaryl bridge. The singly cross-linked beta chain
      species binds oxygen cooperatively with a high oxygen affinity (P50 = 4.8 torr at
      pH 7.4). The addition of the second cross-linking reduces the oxygen affinity to
      15.9 torr, which compares with 13.0 torr for the singly cross-linked alpha chain
      species. The doubly cross-linked hemoglobin retains significant cooperativity
      with a Hill coefficient of 2.3 compared with 3.0 for unmodified hemoglobin.
      Because some of the groups responsible for the Bohr effect are acylated, this
      doubly cross-linked hemoglobin exhibits 25% of the normal Bohr effect and less
      than 20% of the normal chloride effect. The use of two distinct cross-links
      within the same tetramer provides a material for physical and structural analysis
      as well as for further modifications for specific applications. The results
      indicate that the cross-link introducing the lowest oxygen affinity in the two
      singly cross-linked species appears to control the overall affinity in this
      doubly cross-linked species.

PMID- 8557673
TI  - Glyoxal oxidase from Phanerochaete chrysosporium is a new radical-copper oxidase.
AB  - A free radical-coupled copper complex has been identified as the catalytic
      structure in the active site of glyoxal oxidase from Phanerochaete chrysosporium
      based on a combination of spectroscopic and biochemical studies. The native
      (inactive) enzyme is activated by oxidants leading to the elimination of the
      cupric EPR signal consistent with formation of an antiferromagnetically coupled
      radical-copper complex. Oxidation also leads to the appearance of a
      substoichiometric free radical EPR signal with an average g value (gav = 2.0055)
      characteristic of phenoxyl tau-radicals arising from a minority apoenzyme
      fraction. Optical absorption, CD, and spectroelectrochemical measurements on the
      active enzyme reveal complex spectra extending into the near IR and define the
      redox potential for radical formation (E 1/2 = 0.64 V versus NHE, pH 7.0).
      Resonance Raman spectra have identified the signature of a modified (cysteinyl
      tyrosine) phenoxyl in the vibrational spectra of the active complex. This radical
      copper motif has previously been found only in galactose oxidase, with which
      glyoxal oxidase shares many properties despite lacking obvious sequence identity,
      and catalyzing a distinct reaction. The enzymes thus represent members of a
      growing class of free radical metalloenzymes based on the radical-copper
      catalytic motif and appear to represent functional variants that have evolved to
      distinct catalytic roles.

PMID- 8557674
TI  - Kinetic studies of calcium binding to the regulatory site of troponin C from
      cardiac muscle.
AB  - We have studied the kinetics of the structural transitions induced by calcium
      binding to the single, regulatory site of cardiac troponin C by measuring the
      rates of calcium-mediated fluorescence changes with a monocysteine mutant of the
      protein (C35S) specifically labeled at Cys-84 with the fluorescent probe 2(-)[4'
      (iodoacetamido)anilino]naphthalene-6-sulfonic acid. At 4 degrees C, the binding
      kinetics determined in the presence of Mg2+ was resolved into two phases with
      positive amplitude, which were completed in less than 100 ms. The rate of the
      fast phase increased linearly with [Ca2+] reaching a maximum of approximately 590
      s-1, and that of the slow phase was approximately 100 s-1 and did not depend on
      Ca2+ concentration. Dissociation of bound Ca2+ from the regulatory site occurred
      with a rate of 102 s-1, whereas the dissociation from the two high affinity sites
      was about two orders of magnitude slower. These results are consistent with the
      following scheme for the binding of Ca2+ to the regulatory site: [formula: see
      text] where the asterisks denote states with enhanced fluorescence. The apparent
      second-order rate constant for calcium binding is Kok1 = 1.4 x 10(8) M 1 s-1. The
      two first-order transitions occur with observed rates of k1 + kappa-1
      approximately 590 s-1 and kappa 2 + kappa-2 approximately 100 s-1, and the
      binding of Ca2+ to the regulatory site is not a simple diffusion-controlled
      reaction. These transitions provide the first information on the rates of Ca(2+)
      induced conformational changes involving helix movements in the regulatory
      domain.

PMID- 8557675
TI  - Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor.
      Study of Lck- and FynT-dependent T cell activation.
AB  - Here, we have studied the activity of a novel protein-tyrosine kinase inhibitor
      that is selective for the Src family of tyrosine kinases. We have focused our
      study on the effects of this compound on T cell receptor-induced T cell
      activation, a process dependent on the activity of the Src kinases Lck and FynT.
      This compound is a nanomolar inhibitor of Lck and FynT, inhibits anti-CD3-induced
      protein-tyrosine kinase activity in T cells, demonstrates selectivity for Lck and
      FynT over ZAP-70, and preferentially inhibits T cell receptor-dependent anti-CD3
      induced T cell proliferation over non-T cell receptor-dependent phorbol 12
      myristate 13-acetate/interleukin-2 (IL-2)-induced T cell proliferation.
      Interestingly, this compound selectively inhibits the induction of the IL-2 gene,
      but not the granulocyte-macrophage colony-stimulating factor or IL-2 receptor
      genes. This compound offers a useful new tool for examining the role of the Lck
      and FynT tyrosine kinases versus ZAP-70 in T cell activation as well as the role
      of other Src family kinases in receptor function.

PMID- 8557676
TI  - Thrombin receptor activating mutations. Alteration of an extracellular agonist
      recognition domain causes constitutive signaling.
AB  - Constitutively active thrombin receptors were generated while constructing
      chimeric receptors to identify the structural basis for thrombin receptor agonist
      specificity. Substitution of eight amino acids from the Xenopus receptor's second
      extracellular loop (XECL2B) for the cognate sequence in the human thrombin
      receptor was sufficient to confer robust constitutive activity. Smaller
      substitutions within the XECL2B site yielded less constitutive activation, and
      substitution of several unrelated sequences at this site caused no activation.
      Expression of the XECL2B receptor caused high basal 45Ca efflux in Xenopus
      oocytes and high basal phosphoinositide hydrolysis and reporter gene induction in
      COS cells. Of note, a mutant receptor in which all four of the Xenopus thrombin
      receptor's extracellular segments replaced the cognate human sequences showed
      much less constitutive activity than XECL2B and preserved responsiveness to
      agonist. This partial complementation of the XECL2B phenotype by addition of
      other Xenopus extracellular structures suggests that the XECL2B mutation causes
      constitutive activation by altering interactions among the human receptor's
      extracellular domains. Thus, a change in an extracellular loop of a G protein
      coupled receptor can transmit information across the cell membrane to cause
      signaling, perhaps via a conformational change similar to that caused by agonist
      binding. Indeed, the site of the activating mutation in XECL2B coincides with a
      putative agonist-docking site, supporting the hypothesis that agonist
      interactions with the thrombin receptor's extracellular loops contribute to
      receptor activation.

PMID- 8557677
TI  - Members of the caudal family of homeodomain proteins repress transcription from
      the human apolipoprotein B promoter in intestinal cells.
AB  - Apolipoprotein B (apoB) is the major protein component of low density
      lipoproteins, and plays a central role in cholesterol transport and metabolism.
      The apoB gene is transcribed in the liver and in the intestine in humans.
      Although much is known about the DNA sequence elements and protein factors that
      are important for transcription of the human apolipoprotein B gene in the liver,
      less is known about the mechanisms that control transcription of this gene in the
      intestine. The sucrose isomaltase gene (SI), is expressed exclusively in the
      intestine. Two sequences from the promoter region of the SI gene, namely SIF-1
      and SIF-3, are essential for promoter activity of the SI gene in intestinal
      cells. Sequences displaying a high degree of similarity to those of SIF-1 and SIF
      3 are present in the third intron of the apoB gene. Rather than stimulating apoB
      promoter activity, the BSIF-1 and BSIF-3 sequences repressed transcription in
      CaCo-2 cells. Gel retardation studies demonstrated that BSIF-1, like SIF-1, binds
      to proteins related to the caudal family of proteins such as mCdx-4 and mCdx-2.
      These proteins appear to repress transcription from the apoB promoter by a
      mechanism that involves an interaction with members of the C/EBP family of
      proteins, that bind to a target sequence for the repressor in the segment from 
      139 to -111 of the apoB promoter. On the other hand, BSIF-3, like SIF-3, binds to
      HNF-1 and also represses transcription from the apoB promoter.

PMID- 8557678
TI  - Calcium-dependent binding of S100C to the N-terminal domain of annexin I.
AB  - The annexin family of proteins is characterized by a conserved core domain that
      binds to phospholipids in a Ca(2+)-dependent manner. Each annexin also has a
      structurally distinct N-terminal domain that may impart functional specificity.
      To search for cellular proteins that interact with the N-terminal domain of
      annexin I, we constructed a fusion protein consisting of glutathione S
      transferase fused to amino acids 2-47 of human annexin I (GST-AINT; AINT =
      annexin I N-terminal). Extracts from metabolically labeled A431 cells contained a
      single protein (M(r) approximately 10,000) that bound to GST-AINT in a Ca(2+)
      dependent manner. A synthetic peptide corresponding to amino acids 2-18 of
      annexin I inhibited the binding of the 10-kDa protein to GST-AINT with half
      maximal inhibition occurring at approximately 15 microM peptide. In cellular
      extracts, endogenous annexin I and the 10-kDa protein associated in a reversible
      Ca(2+)-dependent manner. Experiments with other annexins and with N-terminal
      truncated forms of annexin I indicated that the 10-kDa protein bound specifically
      to a site within the first 12 amino acids of annexin I. The 10-kDa protein was
      purified from human placenta by hydrophobic and affinity chromatography. Amino
      acid sequence analysis indicated that the 10-kDa protein is the human homologue
      of S100C, a recently identified member of the S100 subfamily of EF-hand Ca(2+)
      binding proteins.

PMID- 8557679
TI  - Isolation and characterization of an endogenous peptide from rat brain
      interacting specifically with the serotonergic 1B receptor subtypes.
AB  - The existence of endogenous compounds interacting with the serotonergic system
      was previously postulated. In the present work, rat brain tissues were extracted
      by acidic and organic procedures. The resulting extract was tested for its
      capacity to interact with the binding of [3H]5-hydroxytryptamine ([3H]5-HT) to 5
      HT1 receptors. Compounds responsible for the observed inhibitory activities were
      isolated and purified by high pressure liquid chromatography. A tetrapeptide
      corresponding to a novel amino acid sequence Leu-Ser-Ala-Leu (LSAL) was
      identified. It reduces the binding of [3H]5-HT to 5-HT1 receptors at low
      concentration (IC50 = 10(-10) M). This effect corresponds to a specific
      interaction at 5-HT1B receptors since LSAL does not significantly affect other
      neurotransmitter bindings. LSAL appears heterogeneously distributed throughout
      the brain (hippocampus > cerebellum > striatum > brain stem) and in peripheral
      tissues (kidney > lung > stomach > blood > liver > spleen). Two other peptides,
      Leu-Ser (LS) and Ala-Leu (AL), were also purified. They hardly affected [3H]5-HT
      binding compared with LSAL. They presumably represent degradation products of the
      functional peptide LSAL. The fact that LSAL interacts specifically with 5-HT1B
      receptors that inhibit the release of neurotransmitters and particularly that of
      5-HT itself suggests that this peptide may be involved in mechanisms controlling
      5-HT neurotransmission and, accordingly, may play an important role in
      pathophysiological functions related to 5-HT activity.

PMID- 8557680
TI  - Interleukin 6 induces the expression of vascular endothelial growth factor.
AB  - Angiogenesis, the formation of new blood vessels, is induced by various growth
      factors and cytokines that act either directly or indirectly. Vascular
      endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial
      cells and therefore has a central role in physiological events of angiogenesis.
      Interleukin-6 (IL-6) expression on the other hand is elevated in tissues that
      undergo active angiogenesis but does not induce proliferation of endothelial
      cells. We demonstrate using Northern analysis that treatment of various cell
      lines with IL-6 for 6-48 h results in a significant induction of VEGF mRNA. The
      level of induction is comparable to the documented induction of VEGF mRNA by
      hypoxia or cobalt chloride, an activator of hypoxia-induced genes. In addition,
      it is demonstrated by transient transfection assays that the effect of IL-6 is
      mediated not only by DNA elements at the promoter region but also through
      specific motif(s) located in the 5'-untranslated region (5'-UTR) of VEGF mRNA.
      Our results imply that IL-6 may induce angiogenesis indirectly by inducing VEGF
      expression. It is also shown that the 5'-UTR is important for the expression of
      VEGF. The 5'-UTR of VEGF is exceptionally long (1038 base pairs) and very rich in
      G + C. This suggests that secondary structures in the 5'-UTR might be essential
      for VEGF expression through transcriptional and post-transcriptional control
      mechanisms.

PMID- 8557681
TI  - Characterization of an unusual Rho factor from the high G + C gram-positive
      bacterium Micrococcus luteus.
AB  - A transcription termination factor (Rho) was purified from the Gram-positive
      bacterium Micrococcus luteus, and the complete gene sequence was determined. The
      M. luteus Rho polypeptide has 690 residues, which is 271 residues more than its
      homolog from Escherichia coli. Most of the additional residues compose a highly
      charged, hydrophilic segment that is inserted in a non-conserved region between
      two conserved regions of the RNA-binding domain of the known Rho homolog
      proteins. This segment extends from residues 49 to 311 and includes a stretch of
      238 residues that contain no hydrophobic side chains. Biochemical studies
      indicate that the M. luteus protein is very similar to E. coli Rho in terms of
      its RNA-dependent NTPase activity and its sensitivity to the Rho-specific
      inhibitor bicyclomycin. However, the M. luteus protein has a less stringent RNA
      cofactor specificity. It also acts to terminate RNA transcription with E. coli
      RNA polymerase on the lambda cro DNA template, but at much earlier termination
      stop points than those recognized by E. coli Rho. Thus, the M. luteus protein
      functions as a true Rho factor, but with a different specificity than that of E.
      coli Rho. We propose that this altered specificity is consistent with its need to
      function on transcripts that have a high content of G + C residues.

PMID- 8557683
TI  - The transmembrane protein-tyrosine phosphatase CD45 is associated with decreased
      insulin receptor signaling.
AB  - Overexpression of the transmembrane protein-tyrosine phosphatase (PTPase) CD45 in
      nonhematopoietic cells results in decreased signaling through growth factor
      receptor tyrosine kinases. Consistent with these data, insulin receptor signaling
      is increased when the CD45-related PTPase LAR is reduced by antisense suppression
      in a rat hepatoma cell line. To test whether the hematopoietic cell-specific
      PTPase CD45 functions in a manner similar to LAR by negatively modulating insulin
      receptor signaling in hematopoietic cells, the insulin-responsive human multiple
      myeloma cell line U266 was isolated into two subpopulations that differed in CD45
      expression. In CD45 nonexpressing (CD45-) cells, insulin receptor
      autophosphorylation was increased by 3-fold after insulin treatment when compared
      to CD45 expressing (CD45+) cells. This increase in receptor autophosphorylation
      was associated with similar increases in insulin-dependent tyrosine kinase
      activation. These receptor level effects were paralleled by postreceptor
      responses. Insulin-dependent tyrosine phosphorylation of insulin receptor
      substrate 1 (IRS-1) and Shc was 3-fold greater in CD45- cells. In addition,
      insulin-dependent IRS-1/phosphatidylinositol 3-kinase association and MAP kinase
      activation in CD45- cells were also 3-fold larger. While expression of CD45 was
      associated with a decrease in the responsiveness of early insulin receptor
      signaling, interleukin 6-dependent activation of mitogen-activated protein kinase
      kinase and mitogen-activated protein kinase was equivalent between CD45- and
      CD45+ cells. These observations indicate that CD45 can function as a negative
      modulator of growth factor receptor tyrosine kinases in addition to its well
      established role as an activator of src family tyrosine kinases.

PMID- 8557682
TI  - The transmembrane protein-tyrosine phosphatase LAR modulates signaling by
      multiple receptor tyrosine kinases.
AB  - Antisense-mediated suppression of the transmembrane protein-tyrosine phosphatase
      (PTPase) LAR has been shown previously to increase insulin-dependent
      phosphatidylinositol 3-kinase (PI 3-kinase) activation by greater than 300% in
      the rat hepatoma cell line McA-RH7777. Here, insulin-dependent insulin receptor
      tyrosine kinase activation was examined with recombinant insulin receptor
      substrate 1 (IRS-1) as the substrate and shown to be 3-fold greater in cells with
      suppressed LAR levels. Consistent with a receptor level effect, in vivo insulin
      dependent tyrosine phosphorylation of both IRS-1 and Shc was increased by a
      similar 3-fold with LAR suppression. These increases in IRS-1 and Shc
      phosphorylation were paralleled by increases in insulin-dependent PI 3-kinase
      association with IRS-1 and activation of the MAP kinase pathway. Reduced LAR
      levels also resulted in increases of over 300% and 250% in epidermal growth
      factor (EGF)- and hepatocyte growth factor (HGF)-dependent receptor
      autophosphorylation, respectively, as well as a severalfold increase in substrate
      tyrosine phosphorylation. In a post-receptor response, EGF- and HGF-dependent MAP
      kinase activation was increased by 300% and 350%, respectively, with LAR
      suppression. Similarly, growth factor-dependent PI 3-kinase activation was
      increased in LAR antisense expressing cells when compared to null vector
      expressing cells. These results demonstrate that the transmembrane PTPase LAR
      modulates ligand-dependent activation of at least three receptor tyrosine
      kinases.

PMID- 8557684
TI  - Effects of myosin light chain kinase and peptides on Ca2+ exchange with the N-
      and C-terminal Ca2+ binding sites of calmodulin.
AB  - Myosin light chain kinase and peptides from the calmodulin (CaM) binding domains
      of myosin light chain kinase (RS-20, M-13), CaM kinase II, and the myristoylated
      alanine-rich protein kinase C substrate protein slowed Ca2+ dissociation from
      CaM's N-terminal sites from 405 +/- 75/s to 1.8-2.9/s and from CaM's C-terminal
      sites from 2.4 +/- 0.2/s to 0.1-0.4/s at 10 degrees C. Since Ca2+ dissociates 5
      29 times faster from the N-terminal in these CaM.peptide complexes and both lobes
      are required for activation, Ca2+ dissociation from the N-terminal would control
      target protein inactivation. Ca2+ binds 70 times faster to the N-terminal (1.6 x
      10(8) M-1 s-1) than the C-terminal sites (2.3 x 10(6) M-1 s-1). In a 0.6-ms half
      width Ca2+ transient, Ca2+ occupied > 70% of the N-terminal but only 20% of the C
      terminal sites. RS-20 produced a 9-fold and CaM kinase II a 6.3-fold increase in
      C-terminal Ca2+ affinity, suggesting that some target proteins may be bound to
      the C-terminal at resting [Ca2+]. When this is the case, Ca2+ exchange with the
      faster N-terminal sites may regulate CaM's activation and inactivation of these
      target proteins during a Ca2+ transient.

PMID- 8557685
TI  - Rad, a novel Ras-related GTPase, interacts with skeletal muscle beta-tropomyosin.
AB  - Rad, a prototypic member of a subfamily of Ras-related GTPases, is overexpressed
      in skeletal muscle of type II diabetic humans. By expression screening of mouse
      embryo and human skeletal muscle cDNA libraries, we found that Rad interacted
      with skeletal muscle beta-tropomyosin. In the mouse skeletal muscle cell line
      C2C12, this interaction was significantly increased by the calcium ionophore
      A23187. A23187 also caused a time- and concentration-dependent decrease in total
      cellular Rad with increased interaction between tropomyosin and Rad in the
      detergent-soluble fraction and the appearance of Rad in the cytoskeleton. In
      C2C12 cells stably overexpressing a putative dominant negative mutant of Rad
      (S105N), there was an increase in the amount of tropomyosin in Rad
      immunoprecipitates. In cells overexpressing wild type Rad, much of Rad was
      associated with the cytoskeleton and was no longer responsive to A23187. In far
      Western blotting and guanine nucleotide saturation studies, GDP-Rad bound to
      tropomyosin far better than GTP-Rad. We conclude that Rad interacts with skeletal
      muscle beta-tropomyosin and the cytoskeleton in a guanine nucleotide-dependent
      manner. These data suggest that Rad may be involved in skeletal muscle motor
      function and cytoskeletal organization.

PMID- 8557686
TI  - Synergistic transcriptional activation of the tissue inhibitor of
      metalloproteinases-1 promoter via functional interaction of AP-1 and Ets-1
      transcription factors.
AB  - The tissue inhibitor of metalloproteinases-1 (TIMP-1) is an inhibitor of the
      extracellular matrix-degrading metalloproteinases. We characterized response
      elements that control TIMP-1 gene expression. One contains a binding site that
      selectively binds c-Fos and c-Jun in vitro and confers a response to multiple AP
      1 family members in vivo. Adjacent to this is a binding site for Ets domain
      proteins. Although c-Ets-1 alone did not activate transcription from this
      element, it enhanced transcription synergistically with AP-1 either in the
      context of the natural promoter or when the sequence was linked upstream of a
      heterologous promoter. Furthermore, a complex of c-Jun and c-Fos interacted with
      c-Ets-1 in vitro. These results suggest that AP-1 tethers c-Ets-1 to the TIMP-1
      promoter via protein-protein interaction to achieve Ets-dependent transcriptional
      regulation. Collectively, our results indicate that TIMP-1 expression is
      controlled by several DNA response elements that respond to variations in the
      level and activity of AP-1 and Ets transcriptional regulatory proteins.

PMID- 8557687
TI  - Substrate specificity of the Escherichia coli 4-aminobutyrate carrier encoded by
      gabP. Uptake and counterflow of structurally diverse molecules.
AB  - Transport of 4-aminobutyrate into Escherichia coli is catalyzed by gab permease
      (GabP). Although published studies show that GabP is relatively specific,
      recognizing the common alpha-amino acids with low affinity, recent work from this
      laboratory indicates that a number of synthetic compounds are high affinity
      transport inhibitors (50% inhibition at 5-100 microM). Here we present evidence
      that many of these structurally heterogeneous compounds not only inhibit
      transport but also function as alternative GabP substrates (i.e. a set of
      observations inconsistent with the idea that the core of the GabP transport
      channel exhibits rigid structural specificity for the native substrate, 4
      aminobutyrate.

PMID- 8557688
TI  - The CDS1 gene encoding CDP-diacylglycerol synthase in Saccharomyces cerevisiae is
      essential for cell growth.
AB  - An open reading frame (CDS1) residing on chromosome II of Saccharomyces
      cerevisiae encodes a hydrophobic protein with a predicted molecular mass of
      51,789 Da, which exhibits 29 and 37% amino acid sequence identities with CDP
      diacylglycerol synthases reported from Escherichia coli and Drosophila,
      respectively. Induction of expression of a GAL1 promoter-driven CDS1 gene on a
      multicopy plasmid in a cds1 null mutant background resulted in synthase activity
      10 times that of wild-type cells and an elevation in the apparent initial rate of
      synthesis of phosphatidylinositol relative to phosphatidylserine. Without
      induction, activity was reduced to 10% of wild-type levels, which was sufficient
      to support growth but resulted in an inositol excretion phenotype, and had an
      opposite effect on the above phospholipid synthesis. Null cds1 mutants were
      incapable of spore germination or vegetative growth and could not be complemented
      under uninduced conditions with a GAL1 promoter-driven CDS1 gene on a low copy
      plasmid. Therefore, the essential CDS1 gene encodes the majority, if not all, of
      the synthase activity. The lack of consensus RNA splice sites derived from the
      genomic CDS1 sequence predicts that the multiple subcellular locations for
      synthase activities do not arise through RNA processing events.

PMID- 8557689
TI  - Isolation and characterization of cDNAs corresponding to two human calcium,
      calmodulin-regulated, 3',5'-cyclic nucleotide phosphodiesterases.
AB  - cDNAs corresponding to two human calcium, calmodulin (CaM)-regulated 3',5'-cyclic
      nucleotide phosphodiesterases (PDEs) were isolated. One, Hcam1 (PDE1A3),
      corresponds to the bovine 61-kDa CaM PDE (PDE1A2). The second, Hcam3 (PDE1C),
      represents a novel phosphodiesterase gene. Hcam1 encodes a 535-amino acid protein
      that differs most notably from the bovine 61-kDa CaM PDE by the presence of a 14
      amino acid insertion and a divergent carboxyl terminus. RNase protection studies
      indicated that Hcam1 is represented in human RNA from several tissues, including
      brain, kidney, testes, and heart. Two carboxyl-terminal splice variants for Hcam3
      were isolated. One, Hcam3b (PDE1C1), encodes a protein 634 amino acids (72 kDa)
      in length. The other, Hcam3a (PDE1C3), diverges from Hcam3b 4 amino acids from
      the carboxyl terminus of Hcam3b, and extends an additional 79 amino acids. All
      the cDNAs isolated for Hcam3a are incomplete; they do not include the 5'-end of
      the open reading frame. Northern analysis revealed that both splice variants were
      expressed in several tissues, including brain and heart, and that there may be
      additional splice variants. Amino-truncated recombinant proteins were expressed
      in yeast and characterized biochemically. Hcam3a has a high affinity for both
      cAMP and cGMP and thus has distinctly different kinetic parameters from Hcam1,
      which has a higher affinity for cGMP than for cAMP. Both PDE1C enzymes were
      inhibited by isobutylmethylxanthine, 8-methoxymethyl isobutylmethylxanthine,
      zaprinast, and vinpocetine.

PMID- 8557690
TI  - Triple-barrel organization of ENaC, a cloned epithelial Na+ channel.
AB  - A cloned rat epithelial Na+ channel (rENaC) was studied in planar lipid bilayers.
      Two forms of the channel were examined: channels produced by the alpha subunit
      alone and those formed by alpha, beta, and gamma subunits. The protein was
      derived from two sources: either from in vitro translation reaction followed by
      Sephadex column purification or from heterologous expression in Xenopus oocytes
      and isolation of plasma membranes. We found that either alpha-rENaC alone or
      alpha- in combination with beta- and gamma-rENaC, produced highly Na(+)-selective
      (PNa/PK = 10), amiloride-sensitive (Kamili = 170 nM), and mechanosensitive cation
      channels in planar bilayers. alpha-rENaC displayed a complicated gating
      mechanism: there was a nearly constitutively open 13-picosiemens (pS) state and a
      second 40-pS level that was achieved from the 13-pS level by a 26-pS transition.
      alpha-, beta-, gamma-rENaC showed primarily the 13-pS level. alpha-rENaC and
      alpha,beta,gamma-rENaC channels studied by patch clamp displayed the same gating
      pattern, albeit with > 2-fold lowered conductance levels, i.e. 6 and 18 pS,
      respectively. Upon treatment of either channel with the sulfhydryl reducing agent
      dithiothreitol, both channels fluctuated among three independent 13-pS sublevels.
      Bathing each channel with a high salt solution (1.5 M NaCl) produced stochastic
      openings of 19 and 38 pS in magnitude between all three conductance levels.
      Different combinations of alpha-, beta-, and gamma-rENaC in the reconstitution
      mixture did not produce channels of intermediate conductance levels. These
      findings suggest that functional ENaC is composed of three identical conducting
      elements and that their gating is concerted.

PMID- 8557691
TI  - Interaction of cardiotonic thiadiazinone derivatives with cardiac troponin C.
AB  - The cardiotonic effects of thiadiazinone derivative EMD 57033 are mediated by
      direct actions on myofilaments (Lues, I., Beier, N., Jonas, R., Klockow, M., and
      Haeusler, G. J. (1993) Cardiovasc. Pharmacol. 21, 883-892). Cardiac troponin C
      has been postulated to be a potential target of the drug (White, J., Lee, J. A.,
      Shah, N., and Orchard, C. H. (1993) Circ. Res. 73, 61-70). This study tested
      whether EMD 57033 interacts directly with recombinant human cardiac TnC (hcTnC).
      EMD 57033 caused concentration-dependent quenching of tyrosine (Tyr) fluorescence
      of hcTnC in the presence of Ca2+ (100 microM) and little change of the
      fluorescence in the presence of Mg2+ (2 mM). Kd for the drug-hcTnC interaction in
      the presence of Ca2+, determined by Tyr fluorescence titrations, was
      approximately 40 microM. The binding of EMD 57033 was stereo-selective: the
      optical isomer of EMD 57033 bound hcTnC much more weakly. The Ca2+ dependence and
      stereo-selectivity of EMD 57033 binding were substantiated by a dialysis-based
      direct binding assay. EMD 57033 was found to interfere with Ca(2+)-dependent
      binding of hydrophobic probe 1,1'-bi-(4-anili-no)naphthalene-5,5'-disulfonate
      (bis-ANS) to hcTnC. The relationships between [Ca2+] and Tyr fluorescence of
      hcTnC and between [Ca2+] and bis-ANS fluorescence in the presence of hcTnC were
      substantially altered by EMD 57033 in the range of [Ca2+] where Ca2+/Mg2+ sites
      of hcTnC were titrated by Ca2+. EMD 57033 was found to bind as tightly to 2
      Ca2+.hcTnC as to 3 Ca(2+).hcTnC. These observations were interpreted as
      indicating that a EMD 57033-binding site is induced by Ca2+ binding, but not Mg2+
      binding, to the Ca2+/Mg2+ sites of hcTnC. The drug-binding site most likely
      resides in the carboxyl domain of hcTnC.

PMID- 8557692
TI  - Molecular chaperones and the centrosome. A role for TCP-1 in microtubule
      nucleation.
AB  - Molecular chaperones play an important role in facilitating the proper maturation
      of many newly synthesized proteins. Here we provide evidence that molecular
      chaperones also participate in regulating the assembly of the microtubule
      cytoskeleton. Via indirect immunofluorescence analysis, both hsp 73 and TCP-1
      localized within the centrosome in interphase and mitotic cells. These proteins,
      along with the centrosome-specific protein, pericentrin, were also present within
      an enriched preparation of centrosomes. Because the centrosome serves as an
      initiation site for microtubule growth, we examined the ability of cells to
      regrow their microtubule network in the presence of hsp 73 or TCP-1 specific
      antibodies. Purified tubulin and GTP were added to cells following the
      depolymerization and extraction of cellular microtubules. Microtubules were
      observed to nucleate off the centrosome using this system, even in the presence
      of anti-hsp 73 antibodies. Incubation with anti-TCP-1 antibodies, however,
      blocked microtubule regrowth off the centrosome. Similarly, anti-TCP-1 antibodies
      microinjected into living cells first treated with nocodazole also inhibited the
      regrowth of the microtubule network following removal of the microtubule poison.
      Our results complement earlier genetic studies in yeast implicating a role for
      TCP-1 in microtubule mediated processes, and may help to explain the previously
      reported mitotic and meiotic abnormalities associated with TCP-1 mutations.

PMID- 8557693
TI  - Molecular chaperones and the centrosome. A role for HSP 73 in centrosomal repair
      following heat shock treatment.
AB  - In the accompanying paper (Brown, C. R., Doxsey, S. J., Hong-Brown, L. W.,
      Martin, R. L., and Welch, W. J. (1996) J. Biol. Chem. 271, 824-832) two molecular
      chaperones, hsp 73 and TCP-1, were shown to be integral components of the
      centrosome. Here we show that heat shock treatment adversely affects both the
      structure and function of the centrosome, and that hsp 73 plays a role in the
      repair of the organelle. After heat shock treatment, the centrosome could not be
      identified via indirect immunofluorescence and cells were unable to support
      microtubule regrowth. During recovery from heat shock, a strong correlation
      between the return of staining of three centrosomal antigens (hsp 73, TCP-1, and
      pericentrin) and the recovery of microtubule regrowth properties was found.
      Incubation of cells with glycerol, a protein protective agent, prevented the heat
      induced alterations in the structure/function of the centrosome. Likewise, the
      recovery of the structure and function of the centrosome after heat shock
      treatment was significantly accelerated in cells first made thermotolerant. We
      provide evidence that this process is related to the levels of hsp 73 since: 1)
      microinjection of hsp 73 antibody blocked centrosomal reassembly and microtubule
      regrowth abilities following heat shock; and 2) microinjection of purified hsp 73
      protein prior to heat shock treatment accelerated both the repair and function of
      the organelle, similar to that observed for thermotolerant cells.

PMID- 8557694
TI  - Mutational analysis of the vacuolar sorting signal of procarboxypeptidase Y in
      yeast shows a low requirement for sequence conservation.
AB  - The core of the vacuolar targeting signal of yeast carboxypeptidase Y (CPY) is
      recognized by the receptor Vps10p and consists of four contiguous amino acid
      residues, Gln24-Arg-Pro-Leu27, near the amino terminus of the propeptide (Valls,
      L.A., Winther, J. R., and Stevens, T. H. (1990) J. Cell Biol. 111, 361-368;
      Marcusson, E. G., Horazdovsky, B. F., Cereghino, J. L., Gharakhanian, E., and
      Emr, S. D. (1994) Cell 77, 579-586). In order to determine the sequence
      specificity of the interaction with the sorting receptor, substitutions were
      introduced into this part of the propeptide by semirandom site-directed
      mutagenesis. The efficiency of vacuolar sorting by the mutants was determined by
      immunoprecipitation of CPY from pulse-labeled cells. It was found that amino acid
      residues Gln24 and Leu27 were the most important ones. While it appears that
      Gln24 is essential for proper function, Leu27 can be exchanged with the other
      hydrophobic amino acid residues, isoleucine, valine, and phenylalanine. Tolerance
      toward various substitutions for Arg25 is fairly high, while substitution of
      Pro26 for uncharged amino acid residues also resulted in only weak missorting. In
      addition to the low requirement for sequence conservation, the position of the
      targeting element relative to the amino terminus of the propeptide was analyzed
      and found not to be critical.

PMID- 8557695
TI  - Selective activation of T cell kinase p56lck by Herpesvirus saimiri protein tip.
AB  - Infection with Herpesvirus saimiri, a T lymphotropic virus of non-human primates,
      immortalizes human T cells in vitro. The cells show a mature activated phenotype
      and retain their antigen specificity. We have previously shown that in H. saimiri
      transformed cells a viral gene product termed tyrosine kinase interacting protein
      (Tip) associates with the T cell-specific tyrosine kinase p56lck and becomes
      phosphorylated by the enzyme on tyrosine residues. Here we show that p56lck is
      activated by recombinant and native Tip in cell-free systems. A dramatic increase
      of Lck activity was also observed in T cell lines transfected with Tip. p60fyn
      and p53/56lyn, the other Src-related kinases expressed in H. saimiri transformed
      T cells, did not phosphorylate Tip, and they were not activated by the protein.
      The selective activation of p56lck by Tip could contribute to the transformed
      phenotype of H. saimiri infected cells, and it might explain the T cell
      selectivity of the transformation event.

PMID- 8557696
TI  - Overexpression of thymidine kinase mRNA eliminates cell cycle regulation of
      thymidine kinase enzyme activity.
AB  - Expression of thymidine kinase (TK) enzyme activity and mRNA is strictly S phase
      specific in primary cells. In contrast, DNA tumor virus-transformed cells have
      enhanced and constitutive levels of TK mRNA during the whole cell cycle. Their TK
      protein abundance, however, still increases at the G1-S transition and stays high
      throughout G2 until mitosis. Therefore, post-transcriptional control must account
      for the decoupling of TK mRNA from protein synthesis in G1. To characterize the
      underlying mechanism, we studied the consequences of TK mRNA abundance on the
      cell cycle-dependent regulation of TK activity in nontransformed cells.
      Constitutive as well as conditional human and mouse TK cDNA vectors were stably
      transfected into mouse fibroblasts, which were subsequently synchronized by
      centrifugal elutriation. Low constitutive TK mRNA expression still resulted in a
      fluctuation of TK activity with a pronounced maximum in S phase. This pattern of
      cell cycle-dependent TK activity variation reflected the one in primary cell but
      is caused by post-transcriptional control. Increasing overexpression of TK
      transcripts after hormonal induction compromised this regulation. At the highest
      constant mRNA levels, regulation of enzyme activity was totally abolished in each
      phase of the cell cycle. These data indicate that post-transcriptional regulation
      of TK is tightly coupled to the amount of mRNA; high concentrations apparently
      titrate a factor(s) required for repressing TK production during G1 and
      presumably also G2.

PMID- 8557697
TI  - The kinetics, substrate, and inhibitor specificity of the monocarboxylate
      (lactate) transporter of rat liver cells determined using the fluorescent
      intracellular pH indicator, 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein.
AB  - The kinetics of transport of L-lactate, pyruvate, ketone bodies, and other
      monocarboxylates into isolated hepatocytes from starved rats were measured at 25
      degrees C using the intracellular pH-sensitive dye, 2',7'-bis(carboxyethyl)- 5(6)
      carboxyfluorescein, to detect the associated proton influx. Transport kinetics
      were similar, but not identical, to those determined using the same technique for
      the monocarboxylate transporter (MCT) of Ehrlich Lettre tumor cells (MCT1)
      (Carpenter, L., and Halestrap, A. P. (1994) Biochem. J. 304, 751-760). Km values
      for L-lactate (4.7 mM), D-lactate (27 mM), D,L-2-hydroxybutyrate (3.3 mM), L-3
      hydroxybutyrate (12.7 mM), and acetoacetate (6.1 mM) were very similar in both
      cell types, whereas in hepatocytes the Km values were higher than MCT1 for
      pyruvate (1.3 mM, cf. 0.72 mM), D-3-hydroxybutyrate (24.7 mM, cf. 10.1 mM), D-2
      chloropropionate (1.3 mM, cf. 0.8 mM), 4-hydroxybutyrate (18.1 mM, cf. 7.7 mM),
      and acetate (5.4 mM, cf. 3.7 mM). In contrast, the hepatocyte carrier had lower
      Km values than MCT1 for glycolate, chloroacetate, dichloroacetate, and 2-hydroxy
      2-methylpropionate. Differences in stereoselectivity were also detected; both
      carriers showed a lower Km for L-lactate than D-lactate, while hepatocyte MCT
      exhibited a lower Km for D- than L-2-chloropropionate and for L- than D-3
      hydroxybutyrate; this is not the case for MCT1. A range of inhibitors of MCT1,
      including alpha-cyanocinnamate derivatives, phloretin, and niflumic acid,
      inhibited hepatocyte MCT with K0.5 values significantly higher than for tumor
      cell MCT1, while stilbene disulfonate derivatives and p-chloromercuribenzene
      sulfonate had similar K0.5 values in both cell types. The branched chain
      ketoacids alpha-ketoisocaproate and alpha-ketoisovalerate were also potent
      inhibitors of hepatocyte MCT with K0.5 values of 270 and 340 microM,
      respectively. The activation energy of L-lactate transport into hepatocytes was
      58 kJ mol-1, and measured rates of transport at 37 degrees C were considerably
      greater than those required for maximal rates of gluconeogenesis. The properties
      of the hepatocyte monocarboxylate transporter are consistent with the presence of
      a distinct isoform of MCT in liver cells as suggested by the cloning and
      sequencing of MCT2 from hamster liver (Garcia, C. K., Brown, M. S., Pathak, R.
      K., and Goldstein, J. L. (1995) J. Biol. Chem. 270, 1843-1849).

PMID- 8557698
TI  - Analysis of the binding of Xenopus transcription factor IIIA to oocyte 5 S rRNA
      and to the 5 S rRNA gene.
AB  - Binding of transcription factor IIIA (TFIIIA) to site-specific mutants of Xenopus
      oocyte 5 S rRNA has been used to identify important recognition elements in the
      molecule. The putative base triple G75:U76:A100 appears to determine the
      conformation of the loop E region whose integrity is especially important for
      binding of the factor. Proximal substitutions in helices IV and V indicate that
      the proper folding of loop E is also dependent on these structures. Mutations in
      helix V affect binding of TFIIIA to 5 S rRNA and to the gene similarly and
      provide evidence that zinc finger 5 makes sequence-specific contact through the
      major groove of both nucleic acids. Although fingers 1-3 are positioned along
      helix IV and loop D, mutations in this region, including those that disrupt the
      tetraloop or close the opening in the major groove of the helix created by the
      U80:U96 mismatch, have no impact on binding. Substitutions made at stem-loop
      junctions in the arm of the RNA comprised of helix II-loop B-helix III display
      minor decreases in affinity for TFIIIA. Despite the alignment of the factor along
      nearly the entire length of 5 S rRNA, the essential elements for high affinity
      binding are limited to the central region of the molecule. Analysis of the
      corresponding mutations in the gene confirm that box C and the intermediate
      element provide the high affinity sites for binding of the factor to the DNA.
      Despite the small thermodynamic contribution made by contacts to box A, mutations
      made in this element can cause substantial changes in the orientation of the
      carboxyl-terminal fingers along the 5'-end of the internal control region.

PMID- 8557699
TI  - Monocyte chemotactic factor in rheumatoid arthritis synovial tissue. Probably a
      cross-linked derivative of S19 ribosomal protein.
AB  - The extracts of rheumatoid arthritis-synovial lesions from seven patients
      possessed a strong chemotactic activity for monocytes and a negligible one for
      polymorphonuclear leukocytes. These results are consistent with a prominent
      histological feature of the synovial lesion, the mononuclear cell predominant
      infiltration. The major monocyte chemotactic factor in the synovial tissue
      extracts was purified to a single protein peak in reverse phase high performance
      liquid chromatography with a C4 column. NH2-terminal amino acid analysis of the
      initial 20 residues yielded a single sequence. Surprisingly, this sequence was
      completely identical to that of S19 ribosomal protein. The purified sample
      demonstrated two protein bands in SDS-polyacrylamide gel electrophoresis with
      apparent molecular masses of 34 and 68 kDa. These sizes were 2 and 4 times that
      of S19 ribosomal protein, suggesting that the chemotactic factor would be a dimer
      or tetramer of S19 ribosomal protein cross-linked by factor XIIIa. A recombinant
      human S19 ribosomal protein was prepared as a fusion protein with a maltose
      binding protein in Escherichia coli. After treatment with factor XIIIa, cross
      linked recombinant S19 ribosomal protein exhibited the monocyte chemotactic
      activity, although the untreated recombinant protein did not.

PMID- 8557700
TI  - Ca2+ pools and cell growth: arachidonic acid induces recovery of cells growth
      arrested by Ca2+ pool depletion.
AB  - The intracellular Ca2+ pump blocker, thapsigargin, induces emptying of Ca2+ pools
      and entry of DDT1MF-2 smooth muscle cells into a quiescent G(0)-like growth
      state. Although thapsigargin blocks pumps essentially irreversibly, high serum
      (20%) induces appearance of new pump protein, return of functional pools, and
      reentry of cells into the cell cycle (Waldron, R. T., Short, A. D., Meadows,
      J.J., Ghosh, T. K., and Gill, D. L. (1994) J. Biol. Chem. 269, 11927-11933).
      Through analysis of the effects of defined serum components and growth
      supplements, we reveal here that the factors in serum responsible for inducing
      recovery of Ca2+ pools and growth in thapsigargin-arrested DDT1MF-2 cells are
      exactly mimicked by the three essential fatty acids, arachidonic, linoleic, and
      alpha-linolenic acids. The EC50 values for arachidonic and linoleic acids on
      growth induction of thapsigargin-arrested cells were the same, approximately 5
      microM. Nonessential fatty acids, including myristic, palmitic, stearic, oleic,
      and arachidic acids, were without any effect. Although not proven to be the
      active component of serum, levels of arachidonic and linoleic acids in serum were
      sufficient to explain serum-induced growth recovery. Significantly, arachidonic
      or linoleic acids induced complete recovery of bradykinin-sensitive Ca2+ pools
      within 6 h of treatment of thapsigargin-arrested cells. Protein synthesis
      inhibitors (cycloheximide or puromycin) completely blocked the appearance of
      serum-induced or arachidonic acid-induced agonist-sensitive pools. The
      sensitivity and fatty acid specificity of Ca2+ pool recovery in thapsigargin
      arrested cells were almost identical to that for growth recovery. No pool or
      growth recovery was observed with 5,8,11,14-eicosatetraynoic acid, the
      nonmetabolizable analogue of arachidonic acid, suggesting that conversion to
      eicosanoids underlies the pool and growth recovery induced by essential fatty
      acids. The results provide not only further information on the link between Ca2+
      pools and cell growth but also evidence for a potentially important signaling
      pathway involved in inducing transition from a stationary to a proliferative
      growth state.

PMID- 8557701
TI  - Functional analysis of conserved histidine residues in Cephalosporium acremonium
      isopenicillin N synthase by site-directed mutagenesis.
AB  - The isopenicillin N synthase of Cephalosporium acremonium (cIPNS) involves a
      catalytically important non-heme iron which is coordinated credibly to histidine
      residues. A comparison of the IPNS genes from various microbial sources indicated
      that there are seven conserved histidine residues. These were individually
      replaced by leucine residues through site-directed mutagenesis, and the sites of
      mutation were confirmed by DNA sequencing. The seven mutant genes were cloned
      separately into the vector pET24d for expression in Escherichia coli BL21 (DE3),
      and the proteins were expressed as soluble enzymes. All the resulting mutant
      enzymes obtained have mobilities of approximately 38 kDa, identical with the wild
      type enzyme on SDS-polyacrylamide gel electrophoresis, and were also reactive to
      cIPNS antibodies. The enzymes were purified by ammonium sulfate precipitation and
      DEAE-Sephadex A-50 ion exchange chromatography, and these were analyzed for
      enzyme activity. A group of mutant enzymes, H49L, H64L, H116L, H126L, and H137L,
      were found to be enzymatically active with reduced activities of 16-93.7%,
      indicating that they are not essential for catalysis. Two of the mutant enzymes,
      H216L and H272L, were found to have lost their enzymatic activity completely,
      indicating that both His-216 and His-272 are crucial for catalysis. It is
      suggested that these histidines are likely to serve as ligands for binding to the
      non-heme iron in the IPNS active site. Alignment of the amino acid sequence of
      IPNS to related non-heme Fe(2+)-requiring enzymes indicated that the two
      essential histidine residues correspond to two invariant residues located in
      highly homologous regions. The conservation of the two closely located histidine
      residues indicates the possible conservation of similar iron-binding sites in
      these enzymes.

PMID- 8557702
TI  - A key role for protein kinase A in homologous desensitization of the beta 2
      adrenergic receptor pathway in S49 lymphoma cells.
AB  - We have used a [3H]forskolin binding assay to assess Gs-adenylyl cyclase
      interactions in intact wild-type (WT) and kin- S49 cells under conditions that
      desensitize the beta 2-adrenergic receptor (beta 2-AR) system. This assay
      provides a measurement of G alpha s-adenylyl cyclase interaction that does not
      rely on the determination of second messenger accumulation or enzyme activity in
      broken cells. Kin- S49 cells lack protein kinase A (PKA) activity and provide a
      unique system in which to study the relative importance of this enzyme in beta 2
      AR desensitization. Although both WT and kin- S49 cells display similar kinetics
      of cAMP accumulation and agonist-induced cell-surface beta 2-AR loss, we found
      that these cell types exhibited very different extents of desensitization of
      forskolin binding following agonist treatment. Specifically, 10 microM
      isoproterenol (37 degrees C, 30 min) induced the loss of 70% of [3H]forskolin
      binding sites in WT cells but only 30% in kin- cells. This loss of sites in WT
      cells displayed a t1/2 of approximately 7 min, was agonist concentration
      dependent (EC50 approximately 60 nM), was not mimicked by 8-Br-cAMP, and could be
      blocked by the PKA inhibitor, H89. The difference between WT and kin- cells in
      agonist-induced desensitization of the beta 2-AR pathway was also noted in
      studies of cAMP accumulation in cells. In addition, preincubation of intact cells
      with isoproterenol did not inhibit guanine nucleotide-dependent [3H]forskolin
      binding in permeabilized cells. Overall, data obtained from [3H]forskolin binding
      assays demonstrate the involvement of PKA in the agonist-dependent uncoupling of
      beta 2-AR and Gs; thus we conclude that PKA plays an important role in the
      homologous desensitization of the beta 2-AR-Gs-adenylyl cyclase pathway in intact
      cells.

PMID- 8557703
TI  - The role of the transcription factor Sp1 in regulating the expression of the
      WAF1/CIP1 gene in U937 leukemic cells.
AB  - The Waf1/Cip1 protein induces cell cycle arrest through inhibition of the
      activity of cyclin-dependent kinases and proliferating cell nuclear antigen.
      Expression of the WAF1/CIP1 gene is induced in a p53-dependent manner in response
      to DNA damage but can also be induced in the absence of p53 by agents such as
      growth factors, phorbol esters, and okadaic acid. WAF1/CIP1 expression in U937
      human leukemic cells is induced by both phorbol ester, a protein kinase C
      activator, and by okaidaic acid, an inhibitor of phosphatases 1 and 2A. Both of
      these agents induce the differentiation of these leukemic cells toward
      macrophages. We demonstrate that phorbol esters and okadaic acid stimulate
      transcription from the WAF1/CIP1 promoter in U937 cells. This transcription is
      mediated by a region of the promoter between -154 and +16, which contains two
      binding sites for the transcription factor Sp1. Deletion or mutation of these Sp1
      sites reduces WAF1/CIP1 promoter response to phorbol ester and okadaic acid,
      while a reporter gene under the control of a promoter containing only multiple
      Sp1 binding sites and a TATA box is induced by phorbol ester and okadaic acid.
      The WAF1/CIP1 promoter is also highly induced by exogenous Sp1 in the Sp1
      deficient Drosophila Schnieder SL 2 cell line. These results suggest that phorbol
      ester and okadaic acid activate transcription of the WAF1/CIP1 promoter through a
      complex of proteins that includes Sp1 and basal transcription factors.

PMID- 8557704
TI  - Degradation of mutant influenza virus hemagglutinins is influenced by cytoplasmic
      sequences independent of internalization signals.
AB  - A mutant influenza virus hemagglutinin, HA+8, having a carboxyl-terminal
      extension of 8 amino acids that included 4 aromatic residues, was internalized
      within 2 min of arriving at the cell surface and was degraded quickly by a
      process that was inhibited by ammonium chloride. Through second-site mutagenesis,
      the internalization sequence of HA+8 was found to closely resemble the
      internalization signals of the transferrin receptor or large mannose 6-phosphate
      receptor. Comparison of the intracellular traffic of HA+8 and a series of other
      HA mutants that differed in their rates of internalization revealed a relation
      between the amount of the protein on the plasma membrane at steady state and the
      internalization rate that would be predicted if most of each protein recycled to
      the cell surface. However, there was no simple correlation between the
      internalization rate and the rate of degradation, indicating that transport to
      the compartment where degradation occurred was not simply a function of the
      concentration of the proteins in early endosomes. The internal populations of
      both HA+8, which was degraded with a t1/2 of 1.9 h, and HA-Y543, which was
      degraded with a t1/2 of 2.9 h, were found by cell fractionation and density-shift
      experiments to reside in early endosomes with little accumulation in lysosomes. A
      fluid-phase marker reached lysosomes 3-4-fold faster than these proteins were
      degraded. Degradation of these mutant HAs involved a rate-determining step in
      early endosomes that was sensitive to some feature of the protein that depended
      upon sequence differences in the cytoplasmic domain unrelated to the
      internalization signal.

PMID- 8557705
TI  - Structure and expression of the mouse necdin gene. Identification of a
      postmitotic neuron-restrictive core promoter.
AB  - Necdin is a 325 amino acid residue protein encoded by a cDNA clone isolated from
      neurally differentiated embryonal carcinoma cells. In situ hybridization
      histochemistry revealed that necdin mRNA-containing cells in vivo coincided with
      postmitotic neurons in the mouse brain from early periods of neurogenesis until
      adulthood. To study the regulation of necdin gene expression, we have isolated
      and characterized the necdin gene from a mouse genomic DNA library. The necdin
      gene contains no intron, and its upstream region lacks canonical TATA and CAAT
      boxes. To assess promoter activity, the 5'-flanking sequence (844 base pairs) of
      the necdin gene was fused to the LacZ reporter gene and transiently transfected
      into retinoic acid-treated P19 embryonal carcinoma cells. Most of the
      transfectants expressing high levels of LacZ immunoreactivity were postmitotic
      neurons differentiated from P19 cells. Deletion analysis using luciferase
      reporter genes demonstrated that a neuron-restrictive core promoter is localized
      to positions -80 to -35, in which a G+C-rich domain and a putative binding site
      for transcription factors with PAS (per, arnt, and single-minded) dimerization
      domain are comprised. These results suggest that postmitotic neuron-restrictive
      expression of the necdin gene is mediated by the specific cis-acting elements and
      that this promoter is applicable to postmitotic neuron-targeted expression of
      various transgenic systems.

PMID- 8557706
TI  - Lys583 in the third extracellular loop of the lutropin/choriogonadotropin
      receptor is critical for signaling.
AB  - The lutropin/choriogonadotropin receptor (LH/CG-R) contains a relatively large
      extracellular domain, in addition to the seven transmembrane helices (TMH), three
      extracellular loops (ECL), and three intracellular loops typical of G protein
      coupled receptors. While high affinity ligand binding has been attributed to the
      N-terminal extracellular domain, there is evidence that portions of the three
      ECLs may function in ligand binding and transmembrane signaling. We have
      investigated the role of several ionizable amino acid residues of rat LH/CG-R in
      human choriogonadotropin (hCG) binding and hCG-mediated cAMP production. COS-7
      cells were transfected with the pSVL expression vector containing cDNAs of either
      wild-type or mutant rat LH/CG-R. Several point mutants of Lys583, located at the
      interface of ECL III and TMH VII, bound hCG like wild-type receptor but exhibited
      greatly diminished ligand-mediated signaling. Neither the point mutant, Lys401-
      >Asp (ECL I), nor the double mutant, Asp397-->Lys/Lys583-->Asp (ECLs I and III,
      respectively, showed significant hCG binding to intact cells; in detergent
      solubilized cells, only the double mutant bound hCG. The mutants Arg341-->Glu
      (interface of the extracellular domain and TMH I) and Lys488-->Glu (ECL II)
      proved to be similar to wild-type receptor in binding and signaling. Our results
      establish that Lys583 is important in signaling but not ligand binding. Its
      location on the opposite side of the membrane from GS precludes a direct
      interaction, thus emphasizing the importance of a conformational change in the
      receptor and suggesting that ligand binding to receptor and ligand-mediated
      receptor activation are dissociable phenomena.

PMID- 8557707
TI  - Genomic organization and chromosomal mapping of the Gal beta 1,3GalNAc/Gal beta
      1,4GlcNAc alpha 2,3-sialyltransferase.
AB  - In this report we describe the chromosome mapping and genomic organization of the
      human Gal beta 1,3GalNAc/Gal beta 1,4GlcNAc alpha 2,3-sialyltransferase gene. The
      gene is localized to human chromosome 11(q23-q24) by in situ hybridization of
      metaphase chromosomes. It spans more than 25 kilobases of human genomic DNA and
      is distributed over 14 exons that range in size from 61 to 679 base pairs.
      Previous characterization of cDNAs encoding the Gal beta 1,3GalNAc/Gal beta
      1,4GlcNAc alpha 2,3-sialyltransferase revealed that the gene produces at least
      three transcripts in human placenta, which code for identical protein sequences
      except at the 5' ends (Kitagawa, H., and Paulson, J. C. (1994a) J. Biol. Chem.
      269, 1394-1401). Repeated screening for clones that contain the 5' end of the
      cDNA has identified two additional distinct mRNAs that are expressed in human
      placenta. Comparison of the genomic DNA sequence with that of the five different
      mRNAs indicates that these transcripts are produced by a combination of
      alternative splicing and alternative promoter utilization. Northern analysis
      indicated that one of them is specifically expressed in placenta, testis, and
      ovary, indicating that its expression is independently regulated from the others.

PMID- 8557708
TI  - Dimerization is required for the activity of the protein histidine kinase CheA
      that mediates signal transduction in bacterial chemotaxis.
AB  - The histidine protein kinase CheA plays an essential role in stimulus-response
      coupling during bacterial chemotaxis. The kinase is a homodimer that catalyzes
      the reversible transfer of a gamma-phosphoryl group from ATP to the N-3 position
      of one of its own histidine residues. Kinetic studies of rates of
      autophosphorylation show a second order dependence on CheA concentrations at
      submicromolar levels that is consistent with dissociation of the homodimer into
      inactive monomers. The dissociation was confirmed by chemical cross-linking
      studies. The dissociation constant (CheA2<==>2CheA; KD = 0.2-0.4 microM) was not
      affected by nucleotide binding, histidine phosphorylation, or binding of the
      response regulator, CheY. The turnover number per active site within a dimer
      (assuming 2 independent sites/dimer) at saturating ATP was approximately 10/min.
      The kinetics of autophosphorylation and ATP/ADP exchange indicated that the
      dissociation constants of ATP and ADP bound to CheA were similar (KD values
      approximately 0.2-0.3 mM), whereas ATP had a reduced affinity for CheA
      approximately P (KD approximately 0.8 mM) compared with ADP (KD approximately 0.3
      mM). The rates of phosphotransfer from bound ATP to the phosphoaccepting
      histidine and from the phosphohistidine back to ADP seem to be essentially equal
      (kcat approximately 10 min-1).

PMID- 8557709
TI  - Plasmalopsychosine of human brain mimics the effect of nerve growth factor by
      activating its receptor kinase and mitogen-activated protein kinase in PC12
      cells. Induction of neurite outgrowth and prevention of apoptosis.
AB  - Plasmalopsychosine, a characteristic fatty aldehyde conjugate of beta
      galactosylsphingosine (psychosine) found in brain white matter, enhances p140trk
      (Trk A) phosphorylation and mitogen-activated protein kinase (MAPK) activity and
      as a consequence induces neurite outgrowth in PC12 cells. The effect of
      plasmalopsychosine on neurite outgrowth and its prolonged activation of MAPK was
      similar to that of nerve growth factor (NGF), and the effect was specific to
      neuronal cells. Plasmalopsychosine was not capable of competing with cold chase
      stable, high affinity binding of NGF to Trk A, indicating that plasmalopsychosine
      and NGF differ in terms of Trk A-activating mechanism. Tyrosine kinase inhibitors
      K-252a and staurosporine, known to inhibit the neurotrophic effect of NGF, also
      inhibited these effects of plasmalopsychosine, suggesting that plasmalopsychosine
      and NGF share a common signaling cascade. Plasmalopsychosine prevents apoptosis
      of PC12 cells caused by serum deprivation, indicating that it has "neurotrophic
      factor-like" activity. Taken together, these findings indicate that
      plasmalopsychosine may play an important role in development and maintenance of
      the vertebrate nervous system.

PMID- 8557710
TI  - Conversion of lysophospholipids to cyclic lysophosphatidic acid by phospholipase
      D.
AB  - Phospholipase D from Streptomyces chromofuscus hydrolyzes lysophosphatidylcholine
      or lysophosphatidylethanolamine in aqueous 1% Triton X-100 solution. In situ
      monitoring of this reaction by 31P NMR revealed the formation of cyclic
      lysophosphatidic acid (1-acyl 2,3-cyclic glycerophosphate) as an intermediate
      which was hydrolyzed further by the enzyme at a functionally distinct active site
      to lysophosphatidic acid (lyso-PA). Synthetic cyclic lyso-PA (1-octanoyl 2,3
      cyclic glycerophosphate) was found to be stable in aqueous neutral solutions at
      room temperature. It was hydrolyzed by the bacterial phospholipase D to lyso-PA
      at a rate which was approximately 4-fold slower than the rate of formation of
      cyclic lyso-PA. The addition of 5-10 mM sodium vanadate could partially inhibit
      the ring opening reaction and thus increase substantially the cyclic lyso-PA
      accumulation. Cyclic lyso-PA may act as a dormant configuration of the
      physiologically active lyso-PA or may even possess specific activities which
      await verification.

PMID- 8557711
TI  - Hydrogen bonding of tyrosine B10 to heme-bound oxygen in Ascaris hemoglobin.
      Direct evidence from UV resonance Raman spectroscopy.
AB  - The hemoglobin from Ascaris suum, a parasitic nematode, has a spontaneous
      dissociation rate for the dioxygen ligand that is 3 orders of magnitude less than
      for mammalian myoglobins or hemoglobins. In this hemoglobin, the distal histidine
      is replaced with a glutamine which is capable of forming a stabilizing hydrogen
      bond to the bound dioxygen. A single hydrogen bond from a glutamine is, under
      typical circumstances, not sufficient to account for the low off rate for oxygen.
      Several studies point to a second hydrogen bond to the heme-bound dioxygen
      originating from tyrosine B10 as the source of this unusual reactivity. In this
      study ultraviolet (UV) resonance Raman spectroscopy is used to directly observe
      the formation of this hydrogen bond upon oxygen binding. The study reveals that
      both oxygen and carbon monoxide induce similar conformational changes in the
      globin upon binding to the heme; however, in the case of oxygen, a strong
      hydrogen bond involving a tyrosine is also observed. Similar studies on the QE7L
      mutant of this Hb suggest that the glutamine plays a role in stabilizing a rigid
      tertiary structure associated with the distal heme pocket. This conformation
      maintains the tyrosine in an orientation conducive to hydrogen bond formation
      with a heme-bound dioxygen ligand.

PMID- 8557712
TI  - Cell cycle regulation of p70 S6 kinase and p42/p44 mitogen-activated protein
      kinases in Swiss mouse 3T3 fibroblasts.
AB  - We show here using synchronized Swiss mouse 3T3 fibroblasts that p70 S6 kinase
      (p70S6k) and mitogen-activated protein kinases (p42mapk/p44mapk) are not only
      activated at the G0/G1 boundary, but also in cells progressing from M into G1.
      p70S6k activity increases 20-fold in G1 cells released from G0. Throughout G1, S,
      and G2 it decreases constantly, so that during M phase low kinase activity is
      measured. The kinase is reactivated 10-fold when cells released from a nocodazole
      induced metaphase block enter G1 of the next cell cycle. p42mapk/p44mapk in G0
      cells are activated transiently early in G1 and are reactivated late in mitosis
      after nocodazole release. p70S6k activity is dependent on permanent signaling
      from growth factors at all stages of the cell cycle. Immunofluorescence studies
      showed that p70S6k and its isoform p85S6k become concentrated in localized spots
      in the nucleus at certain stages in the cell cycle. Cell cycle-dependent changes
      in p70S6k activity are associated with alterations in the phosphorylation state
      of the protein. However, examination of the regulation of a p70S6k mutant in
      which the four carboxyl-terminal phosphorylation sites are changed to acidic
      amino acids suggests that a mechanism independent of these phosphorylation sites
      controls the activity of the enzyme during the cell cycle.

PMID- 8557713
TI  - Structural basis of trimannoside recognition by concanavalin A.
AB  - Despite the fact that complex saccharides play an important role in many
      biological recognition processes, molecular level descriptions of protein
      carbohydrate interactions are sparse. The legume lectin concanavalin A (con A),
      from Canavalia ensiformis, specifically recognizes the trimannoside core of many
      complex glycans. We have determined the crystal structure of a con A-trimannoside
      complex at 2.3-A resolution now describe the trimannoside interaction with conA.
      All three sugar residues are in well defined difference electron density. The 1,6
      linked mannose residue is bound at the previously reported monosaccharide binding
      site; the other two sugars bind in an extended cleft formed by residues Tyr-12,
      Pro-13, Asn-14, Thr-15, and Asp-16. Hydrogen bonds are formed between the protein
      and all three sugar residues. In particular, the 1,3-linked mannose residue makes
      a strong hydrogen bond with the main chain of the protein. In addition, a water
      molecule, which is conserved in other con A structures, plays an important role
      in anchoring the reducing sugar unit to the protein. The complex is further
      stabilized by van der Waals interactions. The structure provides a rationale for
      the high affinity of con A for N-linked glycans.

PMID- 8557714
TI  - Dictyostelium myosin II is regulated during chemotaxis by a novel protein kinase
      C.
AB  - The myosin II heavy chain (MHC)-specific protein kinase C (MHC-PKC) isolated from
      Dictyostelium discoideum has been implicated in the regulation of myosin II
      assembly in response to the chemoattractant, cAMP (Ravid, S., and Spudich, J. A.
      (1989) J. Biol. Chem. 264, 15144-15150). Here we report that elimination of MHC
      PKC results in the abolishment of MHC phosphorylation in response to cAMP. Cells
      devoid of MHC-PKC exhibit substantial myosin II overassembly, as well as aberrant
      cell polarization, chemotaxis, and morphological differentiation. Cells
      overexpressing the MHC-PKC contain highly phosphorylated MHC and exhibit impaired
      myosin II localization and no apparent cell polarization and chemotaxis. The
      results presented here provide direct evidence that MHC-PKC phosphorylates MHC in
      response to cAMP and plays an important role in the regulation of myosin II
      localization during chemotaxis.

PMID- 8557715
TI  - High affinity binding of beta-adrenergic receptor kinase to microsomal membranes.
      Modulation of the activity of bound kinase by heterotrimeric G protein
      activation.
AB  - The beta-adrenergic receptor kinase (beta ARK) modulates beta-adrenergic and
      other G protein-coupled receptors by rapidly phosphorylating agonist-occupied
      receptors at the plasma membrane. We have recently shown that beta ARK also
      associates with intracellular microsomal membranes both "in vitro" and "in situ"
      (Garcia-Higuera, I., Penela, P., Murga, C., Egea, G., Bonay, P., Benovic, J. L.,
      and Mayor, F., Jr. (1994) J. Biol. Chem. 269, 1348-1355), thus suggesting a
      complex modulation of the subcellular distribution of beta ARK. In this report,
      we used recombinant [35S]methionine-labeled beta ARK to show that this kinase
      interacts rapidly with a high affinity binding site (Kd of 20 +/- 1 nM) present
      in salt-stripped rat liver microsomal membranes. Although beta ARK binding is not
      modulated by membrane preincubation with G protein activators, the activity of
      bound beta ARK toward rhodopsin or a synthetic peptide substrate was markedly
      enhanced upon stimulation of the endogenous heterotrimeric G proteins present in
      the microsomal membranes by AIF4- or mastoparan/guanosine 5'-(3-O
      thio)triphosphate, thus strongly suggesting a functional link between these
      proteins and membrane-associated beta ARK. Interestingly, beta ARK association
      with microsomal membranes is not significantly affected by a fusion protein
      derived from the carboxyl terminus of beta ARK1 (the proposed location of the
      beta gamma subunit binding site), whereas it is markedly inhibited by fusion
      proteins corresponding to the amino-terminal region of the kinase. The main
      determinants of binding appear to be localized to an approximately 60-amino acid
      residue stretch (residues 88 to 145). Our results further indicate a functional
      relationship between beta ARK and heterotrimeric G proteins in different
      intracellular organelles, and suggest that additional proteins may be involved in
      modulating the cellular localization of the kinase through a new targeting domain
      of beta ARK.

PMID- 8557716
TI  - Receptors coupled to pertussis toxin-sensitive G-proteins traffic to opposite
      surfaces in Madin-Darby canine kidney cells. A1 adenosine receptors achieve
      apical and alpha 2A adrenergic receptors achieve basolateral localization.
AB  - The alpha 2A adrenergic receptor (alpha 2AAR) previously was shown to be directly
      delivered to and retained on the lateral subdomain of renal epithelial cells. The
      present studies demonstrate that, in contrast, wild-type and epitope-tagged
      canine A1 adenosine receptors (A1AdoR) are apically enriched (65-83%) in Madin
      Darby canine kidney (MDCKII) and porcine renal epithelial (LLC-PKI) cells, based
      on surface biotinylation strategies detecting photoaffinity-labeled A1AdoR.
      Confocal microscopy corroborated the apical enrichment of the epitopetagged
      A1AdoR. Metabolic labeling studies revealed that this steady-state polarization
      is achieved by direct delivery to both the apical (60-75%) and basolateral
      surface. Growth of A1AdoR-expressing cells as monolayers presence of A1AdoR
      antagonists, which decreased cell growth, suggesting that A1AdoR elicit MDCKII
      cell proliferation. The preferential apical but detectable basolateral
      localization of A1AdoR provides a molecular understanding of published reports
      that functional responses can be elicited following apical as well as basolateral
      delivery of adenosine agonists in varying renal preparations. These findings also
      suggest that receptor chimeras derived from the Gi/Go-protein-coupled alpha 2AAR
      and A1AdoR will be informative in revealing structural features critical for
      basolateral versus apical targeting.

PMID- 8557717
TI  - Low-voltage scanning electron microscopic imaging of ultrahigh-molecular-weight
      polyethylene.
AB  - Submicron ultrahigh-molecular-weight polyethylene (UHMWPE) wear particles from
      total joint prostheses may contribute to implant failure through particle
      mediated aseptic loosening. The purpose of this study was to examine the
      microstructure of virgin UHMWPE powder to determine its morphology for future
      comparison with wear debris. A new method of low-voltage scanning electron
      microscopy (LVSEM) in an oil-free vacuum was applied, which produced high
      resolution images of UHMWPE micromorphology, while minimizing specimen damage and
      obviating the need for image processing. GUR 415 UHMWPE virgin powder particles
      were examined by using routine high-voltage SEM, LVSEM, and image analyses. LVSEM
      showed that UHMWPE particles were composed of submicron-size spherical
      subparticles connected by numerous nanometer-size fibrils. These spherical
      subparticles had a highly textured surface morphology seen only by LVSEM.
      Fracture of the nanometer-size fibrils was observed. Routine high-voltage SEM
      obfuscates the intricate and delicate UHMWPE micromorphology as well as the
      damage done by the accompanying high-voltage electrons. This study suggests that
      the micromorphology of wear particles previously studied with routine high
      voltage SEM was overlooked or damaged, justifies the need for LVSEM in future
      studies, and raises the question of what is the true morphology of polyethylene
      wear debris retrieved from human tissues.

PMID- 8557718
TI  - Distribution of titanium and vanadium following repeated injection of high-dose
      salts.
AB  - Titanium and its alloy of 6% aluminium and 4% vanadium are used extensively in
      orthopedic and dental surgery. However, in conditions of motion leading to wear,
      there is significant generation of wear products with deposition of black debris
      in the tissue. The questions remain as to how much of this debris is generated
      and to where it is transported. Previous studies have been hampered by low levels
      of detected elements giving values just above the background levels found in
      normal tissue and body fluids. The purpose of these experiments was to increase
      the body burden of titanium and vanadium by injecting larger doses of titanium
      and vanadium salts over an extended period of time. Each animal (Syrian hamster)
      received 100 micrograms of each element once a week for six weeks. The hamster
      was sacrificed on the seventh week and body fluids and tissue harvested. The
      results indicate that in the experimental animals there was transport of vanadium
      with levels above control in urine, plasma, liver, spleen, and the mineralized
      portion and organic portion of bone. Titanium had less transport but still showed
      levels in the experimental animals in plasma, kidney, liver, spleen, and both
      phases of bone above those in the control animals. Neither element was found
      above control levels in lung or red blood cells. The levels of titanium and
      vanadium in control bone were high, possibly indicating bone as a site for
      storage and accumulation of these elements when encountered in the activities of
      daily living.

PMID- 8557719
TI  - Biomaterial-induced dysfunction in the capacity of rabbit alveolar macrophages to
      kill Staphylococcus epidermidis RP12.
AB  - The effect of poly(methyl methacrylate) (PMMA), titanium alloy, and silicone
      discs on the capacity of rabbit alveolar macrophages (AM) to kill RP12 strain of
      Staphylococcus epidermidis (RP12) was studied in vitro. When freshly harvested AM
      were preincubated with PMMA discs for 3 h and subsequently assayed for RP12
      killing, there was no change in the RP12 killing capacity of AM. However, when AM
      were incubated with PMMA discs for 6 or 18 h at 37 degrees C in 5% CO2, the RP12
      killing capacity of AM was reduced to 15% and 4%, respectively. Preincubation of
      AM with titanium alloy for 6 h reduced RP12 killing capacity of AM to 30%, and to
      21% in 18-h incubation. Silicone discs did not affect the RP12 killing by AM at 6
      h of preincubation, but reduced RP12 killing (35%) by AM when preincubated for 18
      h. Preincubation of AM with PMMA discs for 3 or 6 h did not affect the level of
      PMA-elicited oxidative burst of AM as measured by a luminol-enhanced
      chemiluminescent assay. Superoxide dismutase, which eliminated the oxidative
      burst of AM by 90%, did not affect the RP12 killing by AM.

PMID- 8557720
TI  - An improved model for bacterial encrustation studies.
AB  - A comparative evaluation of various biomaterials for their resistance to
      bacterial colonization and encrustation in infected urine is an important area in
      urological biomaterials research. This article describes an in vitro dynamic
      perfusion system that allows four reactors containing 24 1-in. catheter samples
      (6 per reactor) to be simultaneously perfused at a constant flow rate by
      synthetic urine. A common urease-producing urinary pathogen, Proteus mirabilis,
      was maintained at a level of 10(6) colony-forming units/mL for 7 days in the
      dynamic perfusion reactors. The pH and bacterial population were monitored every
      24 h and the percentage of encrustation on latex and hydrogel-coated commercial
      catheter materials gave reproducible results in three different runs, 15.2 +/-
      3.65% and 13.8 +/- 2.58%, respectively. A major issue of inlet clogging due to
      ascending bacteria or ammonia has been rectified using a dismountable inlet
      assembly. An incubator coupled with a cooling system allowed accurate temperature
      maintenance of 37 degrees C in all four reactors. Results from scanning electron
      microscopy of some latex samples are also presented.

PMID- 8557721
TI  - Endothelial cells on Dacron vascular prostheses: adherence, growth, and
      susceptibility to neutrophils.
AB  - Human umbilical vein endothelial cells (HUVEC) on knitted and woven Dacron
      prostheses were compared with HUVEC on smooth surfaces (tissue culture
      polystyrene, PET film, and Natrix) with regard to adherence, growth, and
      susceptibility to injury by neutrophils (PMN). These are properties of importance
      for successful seeding or coating of prostheses. For prosthetic material of given
      macroscopic dimensions, more endothelial cells (EC) adhered than to smooth
      surfaces. However, the prostheses had a greater effective surface area as
      determined by the number of EC at confluency. When this parameter was taken into
      account, fewer EC were found adherent to prosthetic material per unit effective
      surface area than for the smooth surface substrates. Growth on prostheses was
      clearly inferior to that on smooth surfaces, and EC on prostheses were more
      susceptible to attack by activated PMN than on smooth surfaces. These differences
      may reflect the topographic differences in cells attached to fibers where they
      assume more distorted shapes by stretching to span fibers.

PMID- 8557722
TI  - Degradation of polyetherurethane by subcutaneous implantation into rats. II.
      Changes of contact angles, infrared spectra, and nuclear magnetic resonance
      spectra.
AB  - In vivo degradation of polyetherurethanes (PEUs) was studied using two kinds of
      PEUs, U-3 and U-8, coated on a base film of ethylene/vinyl alcohol copolymer
      (EVAL). U-3 is a nonsegmented PEU prepared from 4,4'-diisocyanatodiphenylmethane
      (MDI) and poly(tetramethylene oxide) (PTMO 1000). U-8 is a segmented PEU prepared
      from MDI, PTMO 1000, and 1,4-butanediol. Previous studies of PEUs were conducted
      using gel permeation chromatography and scanning electron microscopy. In this
      study, the explanted materials were examined with contact angle measurement, ATR
      FTIR, and nuclear magnetic resonance (NMR) spectroscopies. All data obtained by
      these methodologies indicate that the PTMO/MDI oligomers diffused to the material
      surface in the early stage of implantation. Then, the low-molecular-weight
      fraction of the oligomers leached out from the surface to the exudate.
      Degradation became dominant after 2-4 weeks. In the case of PU-8, the PTMO
      fraction decreased approximately 35-40% from the surface at 24 weeks
      postimplantation. In the case of PU-3, the loss of coating material (U-3) on the
      base film (EVAL) was observed after 10 weeks. The PTMO fraction of the surface U
      3 remained on EVAL at 6 weeks postimplantation, however, it was 64% of the
      initial material. The molecular weight of the U-3 remaining on EVAL also
      decreased. Degradation of U-3 occurred more rapidly than that of U-8. The data
      obtained with our materials were insufficient in determining evidence of
      oxidative degradation with IR or NMR spectra.

PMID- 8557723
TI  - Attachment and growth of cultured fibroblast cells on silk protein matrices.
AB  - The attachment and growth of L-929 cells on films made of Bombyx mori silk
      proteins--fibroin and sericin and their mixtures--was studied by a cell culture
      method. Both cell attachment and growth were dependent on a minimum of around 90%
      sericin in the mixture. The results from electron micrography as well as from the
      DSC measurements supported the notion that the mixture of the two proteins
      fibroin and sericin has a phase-separated structure in the solid state. The
      observed minimum of sericin in the cell attachment and growth is thought to be a
      result of this phase-separated structure. Films of pure component proteins (i.e.,
      100% fibroin or sericin) exhibited as high a cell attachment and growth as
      collagen, a widely used mammalian cell culture substrate. However, a
      morphological study of the attached cells revealed that the cells attached to
      silk fibroin were extended and had a spindle shape, just like the cells attached
      to collagen, while the cells attached to the silk sericin had a different shape.
      It is concluded, therefore, that the attachment condition on silk fibroin is
      ideal for the viability, growth and function of the cells.

PMID- 8557724
TI  - Anchorage of TiO2-blasted, HA-coated, and machined implants: an experimental
      study with rabbits.
AB  - The purpose of this study was to evaluate the histometrical and biomechanical
      anchorage of TiO2-blasted implants and TiO2-blasted implants coated with
      hydroxyapatite. The control implants were machined. Twenty-six rabbits had a
      total of 156 implants placed in the proximal part of the tibia. Each rabbit had a
      machined, a TiO2-blasted, and a TiO2-blasted, HA-coated implant placed in each
      tibia. After a healing period of 3 and 12 weeks, respectively, the implants
      placed in the right tibia were used for removal torque test, and the implants
      placed in the left tibia were used for histomorphometrical measurements.
      Preoperatively, implants from the same batches were examined topographically with
      a TopScan 3D system. The TiO2-blasted implants demonstrated significantly higher
      removal torque values than the machined implants, and they also had a
      significantly more irregular surface. Furthermore, significantly higher bone-to
      implant contact length fractions were measured adjacent to the TiO2-blasted
      implants in contrast to the machined implants. The advantages of a TiO2-blasted
      surface were more pronounced after 3 weeks than after 12 weeks. The results
      demonstrated that it was possible to influence the anchorage of implants by
      altering the surface structure morphology. The new method with TiO2 blasting on
      the titanium surface improves the anchorage of implants but is not yet
      practicable for HA coating.

PMID- 8557725
TI  - Cytotoxicity testing of poly(anhydride-co-imides) for orthopedic applications.
AB  - The cytotoxicity of a series of poly(anhydride-co-imides) with osteoblast-like
      cells (MC3T3-E1) was evaluated. The imide component of the copolymers was based
      on trimellitylimidoglycine (TMA-gly), and the anhydride component was based on
      either sebacic acid (SA) or 1,6-bis(carboxyphenoxy)hexane (CPH). Cell adhesion
      and proliferation on surfaces of the polymer discs were observed by environmental
      scanning electron microscopy (ESEM). During the first 24 h of attachment, cells
      showed normal morphology when cultured on the various copolymers of CPH.
      Concurrently, the effects of polymer breakdown products on osteoblast-like cells
      were evaluated by studying their proliferation (cell numbers), viability (dye
      exclusion), and morphology (light microscopy). Cell cultures in the presence of
      these breakdown products resulted in normal morphologies and reached confluency
      after 7 days. This initial in vitro evaluation with osteoblast-like cells
      suggests that the poly(anhydride-co-imides) may be viable carriers for
      osteoblasts.

PMID- 8557726
TI  - Analysis of a vinyl pyrrolidone/poly(propylene fumarate) resorbable bone cement.
AB  - A resorbable bone cement was formulated from N-vinyl-2-pyrrolidinone (VP), the
      unsaturated polyester poly(propylene fumarate) (PPF), and the inorganic filler
      tribasic calcium phosphate (hydroxy apatite). Cure, initiated by benzoyl peroxide
      and accelerated by N,N-dimethyl-p-toluidine, resulted in the formation of VP
      crosslinks between polyester chains. During cure the cement hardened from a
      viscous moldable putty to a rigid structure with a shore D hardness of 50-60. The
      purpose of this study was to determine the fractions of PPF and VP incorporated
      into the crosslinked structure. Dissolution of the cured cement in water followed
      by extraction of the residue in tetrahydrofuran indicated that over 90% of the
      PPF was crosslinked over the range of PPF/VP ratios explored, but that the
      fraction of VP used in formation of crosslinks depended linearly on the PPF/VP
      ratio. Kinetic analysis of these data suggests that k'pp/kpf (the reactivity
      ratio) was approximately 2.0 where k'pp is the rate constant for the addition of
      VP radical to VP monomer leading to formation of poly(vinyl pyrrolidone), and kpf
      is for the addition of VP radical to PPF unsaturation.

PMID- 8557727
TI  - Prevention of bone loss by percutaneous estradiol implants in ovariectomized
      rats.
AB  - This study was conducted to investigate whether hydroxyapatite (HAP) is
      appropriate as a percutaneous drug carrier for estradiol (E2) for the suppression
      of bone loss. Ten-week-old female Sprague-Dawley rats were subjected either to
      bilateral ovariectomy (OVX) or to sham surgery (control). Ovariectomized rats
      were implanted percutaneously with E2-HAP disks containing low, medium or high
      doses of estradiol (50, 250, or 500 micrograms E2/rat, respectively).
      Ovariectomized rats without implant and OVX rats implanted only with HAP served
      as additional controls. All rats were sacrificed 90 days after surgery. At the
      end of the experiment, bone mineral density of the lumbar spine was measured by
      dual energy X-ray absorption, and serum E2 was assayed by radioimmunoassay. The
      bone mineral density of OVX and HAP-treated OVX rats decreased by 18% compared to
      sham surgery rats, but decreased by only 13, 7, and 3% in rats treated with 50,
      250, and 500 micrograms E2/rat, respectively. The in vitro release of E2 from E2
      HAP devices was determined by an HPLC method. Estradiol release from the HAP
      devices followed almost a zero-order kinetics. Estradiol remained intact in E2
      HAP implants for up to six months when stored at 5, 25, and 40 degrees C. This
      study indicates that E2-HAP implants are effective in suppressing bone loss in
      the spine of OVX rats in a dose-dependent manner.

PMID- 8557728
TI  - Antithrombin activity of surface-bound heparin studied under flow conditions.
AB  - Polyacrylamide-grafted polyetherurethane sheets were modified by end-point and
      multipoint attachment of heparin. The surface-bound heparin was firmly attached.
      No release of heparin activity could be detected when the surface was rinsed at a
      wall shear rate of 2000 s-1. Uptake of antithrombin and thrombin inactivation
      were investigated under well-defined flow conditions by the use of a spinning
      device with an attached disk-shaped heparinized surface. It is demonstrated that
      the rate of thrombin inactivation at the antithrombin-heparin surface equals the
      maximal rate of transport of thrombin toward the surface when the surface
      coverage of antithrombin exceeds 10 pmol/cm2. This result indicates that a higher
      intrinsic catalytic efficiency of a surface does not necessarily result in a
      higher antithrombin activity. We varied the heparin content of the surfaces
      between 0 and 35 micrograms/cm2 by increasing the number of functional groups to
      which heparin could be covalently attached. The uptake of antithrombin increased
      with the heparin content of the surface, but the stoichiometry decreased from 2
      to 0.5 pmol antithrombin/micrograms heparin. Apparently, antithrombin could not
      bind to heparins buried in the poly(acrylamide) layer. The rate of thrombin
      inactivation at surfaces with low heparin content (2 micrograms/cm2) fells below
      the transport limit of thrombin and became proportional with the heparin content
      of the surface. Although the contribution of surface-bound heparin to the
      neutralization of fluid-phase thrombin was found to be negligible compared with
      the effect of fluid-phase antithrombin at physiologic relevant concentrations,
      these heparinized surfaces markedly delayed the onset of thrombin generation in
      platelet-rich plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8557729
TI  - Role for interleukin-4 in foreign-body giant cell formation on a
      poly(etherurethane urea) in vivo.
AB  - Interleukin-4 (IL-4) was previously shown to induce extensive macrophage fusion
      to form foreign-body giant cells (FBGCs) in vitro. In the present study, our goal
      was to extend these findings to an in vivo test environment on biomaterials. The
      subcutaneous cage-implant system was modified for mice to elucidate IL-4
      participation in mediating FBGC formation in vivo. Exudate leukocyte
      concentrations from cages containing poly(etherurethane urea) (PEUU A') and empty
      cage controls indicated a similar inflammatory response that turned toward
      resolution by 14 days postimplantation, thus confirming the applicability of the
      cage-implant system in mice. FBGC kinetic analysis showed that the formation of
      mouse FBGCs occurs through the fusion of adherent macrophages at a constant rate
      up to 14 days of implantation. Purified goat anti-mouse IL-4 neutralizing
      antibody (IL4Ab) or normal goat nonspecific control IgG (gtIgG) at various
      concentrations, or recombinant murine IL-4 (muIL4) was injected into the
      implanted cages containing PEUU A' every 2 days for 7 days. The injection of
      IL4Ab significantly decreased the FBGC density on PEUU A' cage-implanted in mice,
      when compared with the nonspecific IgG or PBS injection controls. Conversely, the
      FBGC density was significantly increased by the injection of muIL4 when compared
      with nonspecific IgG and PBS injection controls. Adherent macrophage density,
      FBGC morphology, FBGC average size, and size distribution were not significantly
      different among IL4Ab, nonspecific control gtIgG, muIL4, and PBS control groups.
      Our data suggest that IL-4 participates in FBGC formation on biomaterials in
      vivo.

PMID- 8557730
TI  - Surface-modified poly(methyl methacrylate) enhances adsorption and retains
      anticandidal activities of salivary histatin 5.
AB  - Denture-induced stomatitis is a common intraoral disease which is associated with
      high levels of Candida albicans adhesion to a denture surface. The aim of this
      study was to produce a surface-modified denture resin, which is usually
      manufactured from poly(methyl methacrylate) (PMMA), carrying an immobilized
      anticandidal protein. PMMA was modified by surface polymerization of methyl
      methacrylic acid to enhance adsorption of a potent candidacidal salivary protein,
      histatin 5. The modified PMMA showed higher surface adsorption and desorption of
      histatin 5 than the unmodified material. Because histatin 5 destabilizes C.
      albicans cell membranes and allows efflux of intracellular molecules,
      candidacidal activity was monitored by dye release from fungal cells. Adsorbed
      histatin 5 did not release dye from the yeast cells; however, dye was detected as
      histatin was desorbed from the surface. In an adhesion assay, modified PMMA
      decreased human submandibular-sublingual saliva (HSMSL) mediated adherence of
      yeast cells to the polymer. Precoating histatin 5 onto unmodified PMMA also
      abolished HSMSL-mediated adhesion. These experiments show that dental acrylic may
      be surface modified and loaded with histatin 5 as a means of controlled release
      of histatin 5 to an affected area. This surface modification may additionally
      reduce adhesion of C. albicans cells to the saliva-coated material.

PMID- 8557731
TI  - Structural evaluation of human and sheep bone and comparison with synthetic
      hydroxyapatite by FT-Raman spectroscopy.
AB  - The composition of whole human and sheep cortical bone tissue, and of a synthetic
      hydroxyapatite (P120), were compared using Fourier transform Raman (FT-Raman)
      spectroscopy. Deproteination procedures to remove the bulk of the collagen
      present in bone tissue allowed isolation of the mineral phase. A comparison of
      the spectra obtained from both whole and deproteinated bone with those of
      synthetic hydroxyapatite showed direct correlation only in the region of 952 cm-1
      (symmetric P-O mode). In contrast, human and sheep bone were very closely matched
      in both, the organic and inorganic structures. The results demonstrate that
      deproteination of bone is not a necessary precursor to obtain spectral
      information.

PMID- 8557732
TI  - Surface microarchitectural design in biomedical applications: preparation of
      microporous polymer surfaces by an excimer laser ablation technique.
AB  - In this report we demonstrate a microprocessing method to prepare microporous
      polymer films by an excimer laser ablation technique, which may enable the
      fabrication of functional biomedical devices such as advanced artificial organs.
      The irradiation of a KrF excimer laser pulses (wave-length 248 nm; fluence 1
      J/cm2 pulse) onto several polymer films was achieved by passing a laser pulse
      through an optical microscope, resulting in the formation of an etched pit on the
      irradiated surface due to ablative photodecomposition. The number of pulses and
      the micropositioning of the irradiation were precisely controlled by a computer
      aided control unit. Minimal ablation was observed for polyethylene with very
      small absorption coefficient (alpha) at 248 nm. For polymers which absorbed the
      laser photons, the etch depth increased linearly with number of pulses. The etch
      depth per pulse decreased with an increase in alpha values. An excellent
      structural quality, with micron-order precision of an etched pit, was found for
      those polymers with larger alpha values, such as polyimide, segmented
      polyurethane, and polycarbonate.

PMID- 8557733
TI  - Contact activation during incubation of five different polyurethanes or glass in
      plasma.
AB  - During blood-material interaction, the enzymes factor XII fragment (factor XIIf)
      and kallikrein are generated (contact activation). In this study, the enzymatic
      activities of factor XIIf and kallikrein were examined with an assay based on the
      conversion of tripeptide-p-nitroanilide substrate. With the use of aprotinin to
      inhibit kallikrein, the proteolytic activities of factor XIIf and kallikrein
      could be separately determined. In this in vitro study, two commercially
      available polyurethanes, Pellethane and Biomer; three custom synthesized
      polyurethanes; a biomerlike 2000 MW polytetramethyleneoxide containing
      polyurethane (PU-2000); an octadecyl extended (ODCE) biomer-like 2000 MW
      polytetramethyleneoxide containing polyurethane (PU-2000-ODCE); a hard-segment
      polyurethane (HS-PU); and glass (reference material) were incubated in 25%
      diluted plasma. In both series of experiments, glass caused the highest
      amidolytic activities by factor XIIf and kallikrein compared with any of the
      polyurethanes. In contrast, within the polyurethane group of materials, lower
      amidolytic activities by factor XIIf and kallikrein were measured on the custom
      made polyurethanes than on the commercially available polyurethanes, although the
      differences among the polyurethanes were small. In addition, the influence of
      different ratios of material surface to the plasma incubation volume was studied.
      An increased ratio of surface area over plasma volume resulted in reduced contact
      activation, suggesting that plasma components are the limiting factor.

PMID- 8557734
TI  - Nonrandom gene organization: structural arrangements of specific pre-mRNA
      transcription and splicing with SC-35 domains.
AB  - This work demonstrates a highly nonrandom distribution of specific genes relative
      to nuclear domains enriched in splicing factors and poly(A)+ RNA, and provides
      evidence for the direct involvement of these in pre-mRNA metabolism. As
      investigated in hundreds of diploid fibroblasts, human collagen I alpha 1 and
      beta-actin DNA/RNA showed a very high degree of spatial association with SC-35
      domains, whereas three nontranscribed genes, myosin heavy chain, neurotensin, and
      albumin, showed no such preferential association. Collagen I alpha 1 RNA
      accumulates within the more central region of the domain, whereas beta-actin RNA
      localizes at the periphery. A novel approach revealed that collagen RNA tracks
      are polarized, with the entire gene at one end, on the edge of the domain, and
      the RNA extending into the domain. Intron 26 is spliced within the RNA track at
      the domain periphery. Transcriptional inhibition studies show both the structure
      of the domain and the gene's relationship to it are not dependent upon the
      continued presence of accumulated collagen RNA, and that domains remaining after
      inhibition are not just storage sites. Results support a model reconciling light
      and electron microscopic observations which proposes that transcription of some
      specific genes occurs at the border of domains, which may also function in the
      assembly or distribution of RNA metabolic components. In contrast to the
      apparently random dispersal of total undefined hnRNA synthesis through
      interdomain space, transcription and splicing for some genes occurs
      preferentially at specific sites, and a high degree of individual pre-mRNA
      metabolism is compartmentalized with discrete SC-35 domains.

PMID- 8557735
TI  - Dynamic localization of RNase MRP RNA in the nucleolus observed by fluorescent
      RNA cytochemistry in living cells.
AB  - The dynamic intra-nuclear localization of MRP RNA, the RNA component of the
      ribonucleoprotein enzyme RNase MRP, was examined in living cells by the method of
      fluorescent RNA cytochemistry (Wang, J., L.-G. Cao, Y.-L. Wang, and T. Pederson.
      1991. Proc. Natl. Acad. Sci. USA. 88:7391-7395). MRP RNA very rapidly accumulated
      in nucleoli after nuclear microinjection of normal rat kidney (NRK) epithelial
      cells. Localization was specifically in the dense fibrillar component of the
      nucleolus, as revealed by immunocytochemistry with a monoclonal antibody against
      fibrillarin, a known dense fibrillar component protein, as well as by digital
      optical sectioning microscopy and 3-D stereo reconstruction. When MRP RNA was
      injected into the cytoplasm it was not imported into the nucleus. Nuclear
      microinjection of mutant MRP RNAs revealed that nucleolar localization requires a
      sequence element (nucleotides 23-62) previously implicated as a binding site for
      a nucleolar protein, the To antigen. These results demonstrate the dynamic
      localization of MRP RNA in the nucleus and provide important insights into the
      nucleolar targeting of MRP RNA.

PMID- 8557736
TI  - Nup120p: a yeast nucleoporin required for NPC distribution and mRNA transport.
AB  - To extend our understanding of the mechanism by which the nuclear pore complex
      (NPC) mediates macromolecular transport across the nuclear envelope we have
      focused on defining the composition and molecular organization of the yeast NPC.
      Peptide sequence analysis of a polypeptide with a M(r) of approximately 100,000
      present in a highly enriched yeast NPC fraction identified a novel yeast
      nucleoporin we term Nup120p. Nup120p corresponds to the open reading frame (ORF)
      YKL057c identified by the yeast genome sequencing project. The ORF predicts a
      protein with a calculated molecular mass of 120.5 kD containing two leucine
      zipper motifs, a short coiled-coil region and limited primary sequence similarity
      to Nup133p. Nup120p was localized to the NPC using a protein A-tagged chimera in
      situ by indirect immunofluorescence microscopy. Deletion of the NUP120 gene
      caused clustering of NPCs at one side of the nuclear envelope, moderate nucleolar
      fragmentation and slower cell growth. Transfer of nup120 delta cells to 37
      degrees C resulted in the nuclear accumulation of poly(A)+ mRNA, extensive
      fragmentation of the nucleolus, spindle defects, and cell death.

PMID- 8557737
TI  - Nuclear pore complex clustering and nuclear accumulation of poly(A)+ RNA
      associated with mutation of the Saccharomyces cerevisiae RAT2/NUP120 gene.
AB  - To identify genes involved in the export of messenger RNA from the nucleus to the
      cytoplasm, we used an in situ hybridization assay to screen temperature-sensitive
      strains of Saccharomyces cerevisiae. This identified those which accumulated
      poly(A)+ RNA in their nuclei when shifted to the non-permissive temperature of 37
      degrees C. We describe here the properties of yeast strains carrying mutations in
      the RAT2 gene (RAT - ribonucleic acid trafficking) and the cloning of the RAT2
      gene. Only a low percentage of cells carrying the rat2-1 allele showed nuclear
      accumulation of poly(A)+ RNA when cultured at 15 degrees or 23 degrees C, but
      within 4 h of a shift to the nonpermissive temperature of 37 degrees C, poly(A)+
      RNA accumulated within the nuclei of approximately 80% of cells. No defect was
      seen in the nuclear import of a reporter protein bearing a nuclear localization
      signal. Nuclear pore complexes (NPCs) are distributed relatively evenly around
      the nuclear envelope in wild-type cells. In cells carrying either the rat2-1 or
      rat2-2 allele, NPCs were clustered together into one or a few regions of the
      nuclear envelope. This clustering was a constitutive property of mutant cells.
      NPCs remained clustered in crude nuclei isolated from mutant cells, indicating
      that these clusters are not able to redistribute around the nuclear envelope when
      nuclei are separated from cytoplasmic components. Electron microscopy revealed
      that these clusters were frequently found in a protuberance of the nuclear
      envelope and were often located close to the spindle pole body. The RAT2 gene
      encodes a 120-kD protein without similarity to other known proteins. It was
      essential for growth only at 37 degrees C, but the growth defect at high
      temperature could be suppressed by growth of mutant cells in the presence of high
      osmolarity media containing 1.0 M sorbitol or 0.9 M NaCl. The phenotypes seen in
      cells carrying a disruption of the RAT2 gene were very similar to those seen with
      the rat2-1 and rat2-2 alleles. Epitope tagging was used to show that Rat2p is
      located at the nuclear periphery and co-localizes with yeast NPC proteins
      recognized by the RL1 monoclonal antibody. The rat2-1 allele was synthetically
      lethal with both the rat3-1/nup133-1 and rat7-1/nup159-1 alleles. These results
      indicate that the product of this gene is a nucleoporin which we refer to as
      Rat2p/Nup120p.

PMID- 8557738
TI  - The GLFG repetitive region of the nucleoporin Nup116p interacts with Kap95p, an
      essential yeast nuclear import factor.
AB  - Nup116p is a member of a family of five yeast nuclear pore complex (NPC) proteins
      that share an amino terminal region of repetitive tetrapeptide "GLFG" motifs.
      Previous experiments characterized the unique morphological perturbations that
      occur in a nup116 null mutant: temperature-sensitive formation of nuclear
      envelope seals over the cytoplasmic face of the NPC (Wente, S. R., and G. Blobel.
      1993. J. Cell Biol. 123:275-284). Three approaches have been taken to dissect the
      structural basis for Nup116p's role in NPC function. First, deletion mutagenesis
      analysis of NUP116 revealed that the GLFG region was required for NPC function.
      This was not true for the other four yeast GLFG family members (Nup49p, Nup57p,
      Nup100p, and Nup145p). Moreover, deletion of either half of Nup116p's GLFG
      repeats or replacement of Nup116p's GLFG region with either Nup100p's GLFG region
      or Nsp1p's FXFG repetitive region abolishes the function of Nup116p. At a
      semipermissive growth temperature, the cells lacking Nup116p's GLFG region
      displayed a diminished capacity for nuclear import. Second, overexpression of
      Nup116p's GLFG region severely inhibited cell growth, rapidly blocked
      polyadenylated-RNA export, and fragmented the nucleolus. Although it inhibited
      nuclear export, the overexpressed GLFG region appeared predominantly localized in
      the cytoplasm and NPC/nuclear envelope structure was not perturbed in thin
      section electron micrographs. Finally, using biochemical and two-hybrid analysis,
      an interaction was characterized between Nup116p's GLFG region and Kap95p, an
      essential yeast homologue of the vertebrate nuclear import factor
      p97/Imp90/karopherin beta. These data show that Nup116p's GLFG region has an
      essential role in mediating nuclear transport.

PMID- 8557739
TI  - Characterization of a cis-Golgi matrix protein, GM130.
AB  - Antisera raised to a detergent- and salt-resistant matrix fraction from rat liver
      Golgi stacks were used to screen an expression library from rat liver cDNA. A
      full-length clone was obtained encoding a protein of 130 kD (termed GM130), the
      COOH-terminal domain of which was highly homologous to a Golgi human auto
      antigen, golgin-95 (Fritzler et al., 1993). Biochemical data showed that GM130 is
      a peripheral cytoplasmic protein that is tightly bound to Golgi membranes and
      part of a larger oligomeric complex. Predictions from the protein sequence
      suggest that GM130 is an extended rod-like protein with coiled-coil domains.
      Immunofluorescence microscopy showed partial overlap with medial- and trans-Golgi
      markers but almost complete overlap with the cis-Golgi network (CGN) marker,
      syntaxin5. Immunoelectron microscopy confirmed this location showing that most of
      the GM130 was located in the CGN and in one or two cisternae on the cis-side of
      the Golgi stack. GM130 was not re-distributed to the ER in the presence of
      brefeldin A but maintained its overlap with syntaxin5 and a partial overlap with
      the ER-Golgi intermediate compartment marker, p53. Together these results suggest
      that GM130 is part of a cis-Golgi matrix and has a role in maintaining cis-Golgi
      structure.

PMID- 8557740
TI  - In vitro reconstitution of cytoplasm to vacuole protein targeting in yeast.
AB  - Although the majority of known vacuolar proteins transit through the secretory
      pathway, two vacuole-resident proteins have been identified that reach this
      organelle by an alternate pathway. These polypeptides are targeted to the vacuole
      directly from the cytoplasm by a novel import mechanism. The best characterized
      protein that uses this pathway is aminopeptidase I (API). API is synthesized as a
      cytoplasmic precursor containing an amino-terminal propeptide that is cleaved off
      when the protein reaches the vacuole. To dissect the biochemistry of this
      pathway, we have reconstituted the targeting of API in vitro in a permeabilized
      cell system. Based on several criteria, the in vitro import assay faithfully
      reconstitutes the in vivo reaction. After incubation under import conditions, API
      is processed by a vacuolar-resident protease, copurifies with a vacuole-enriched
      fraction, and becomes inaccessible to the cytoplasm. These observations
      demonstrate that API has passed from the cytoplasm to the vacuole. The
      reconstituted import process is dependent on time, temperature, and energy. ATP
      gamma S inhibits this reaction, indicating that API transport is ATP driven. API
      import is also inhibited by GTP gamma S, suggesting that this process may be
      mediated by a GTP-binding protein. In addition, in vitro import requires a
      functional vacuolar ATPase; import is inhibited both in the presence of the
      specific V-ATPase inhibitor bafilomycin A1, and in a yeast strain in which one of
      the genes encoding a V-ATPase subunit has been disrupted.

PMID- 8557741
TI  - Vesicle accumulation and exocytosis at sites of plasma membrane disruption.
AB  - Plasma membrane disruptions are resealed by an active molecular mechanism thought
      to be composed, in part, of kinesin, CaM kinase, snap-25, and synaptobrevin. We
      have used HRP to mark the cytoplasmic site of a mechanically induced plasma
      membrane disruption. Transmission electron microscopy revealed that vesicles of a
      variety of sizes rapidly (s) accumulate in large numbers within the cytoplasm
      surrounding the disruption site and that microvilli-like surface projections
      overlie this region. Scanning electron microscopy confirmed that tufts of
      microvilli rapidly appear on wounded cells. Three assays, employing the membrane
      specific dye FM1-43, provide quantitative evidence that disruption induces Ca(2+)
      dependent exocytosis involving one or more of the endosomal/lysosomal
      compartments. Confocal microscopy revealed the presence in wounded cells of
      cortical domains that were strikingly depleted of FM dye fluorescence, suggesting
      that a local bolus of exocytosis is induced by wounding rather than global
      exocytosis. Finally, flow cytometry recorded a disruption-induced increase in
      cell forward scatter, suggesting that cell size increases after injury. These
      results provide the first direct support for the hypothesis that one or more
      internal membrane compartments accumulate at the disruption site and fuse there
      with the plasma membrane, resulting in the local addition of membrane to the
      surface of the mechanically wounded cell.

PMID- 8557742
TI  - Calcium-regulated exocytosis is required for cell membrane resealing.
AB  - Using confocal microscopy, we visualized exocytosis during membrane resealing in
      sea urchin eggs and embryos. Upon wounding by a laser beam, both eggs and embryos
      showed a rapid burst of localized Ca(2+)-regulated exocytosis. The rate of
      exocytosis was correlated quantitatively with successfully resealing. In embryos,
      whose activated surfaces must first dock vesicles before fusion, exocytosis and
      membrane resealing were inhibited by neurotoxins that selectively cleave the
      SNARE complex proteins, synaptobrevin, SNAP-25, and syntaxin. In eggs, whose
      cortical vesicles are already docked, vesicles could be reversibly undocked with
      externally applied stachyose. If cortical vesicles were undocked both exocytosis
      and plasma membrane resealing were completely inhibited. When cortical vesicles
      were transiently undocked, exposure to tetanus toxin and botulinum neurotoxin
      type C1 rendered them no longer competent for resealing, although botulinum
      neurotoxin type A was still ineffective. Cortical vesicles transiently undocked
      in the presence of tetanus toxin were subsequently fusion incompetent although to
      a large extent they retained their ability to redock when stachyose was diluted.
      We conclude that addition of internal membranes by exocytosis is required and
      that a SNARE-like complex plays differential roles in vesicle docking and fusion
      for the repair of disrupted plasma membrane.

PMID- 8557743
TI  - Dominant negative effect of cytoplasmic actin isoproteins on cardiomyocyte
      cytoarchitecture and function.
AB  - The intracompartmental sorting and functional consequences of ectopic expression
      of the six vertebrate actin isoforms was investigated in different types of
      cultured cells. In transfected fibroblasts all isoactin species associated with
      the endogenous microfilament cytoskeleton, even though cytoplasmic actins also
      showed partial localization to peripheral submembranous sites. Functional and
      structural studies were performed in neonatal and adult rat cardiomyocytes. All
      the muscle isoactin constructs sorted preferentially to sarcomeric sites and, to
      a lesser extent, also to stress-fiber-like structures. The expression of muscle
      actins did not interfere with cell contractility, and did not disturb the
      localization of endogenous sarcomeric proteins. In sharp contrast, ectopic
      expression of the two cytoplasmic actin isoforms resulted in rapid cessation of
      cellular contractions and induced severe morphological alterations characterized
      by an exceptional outgrowth of filopodia and cell flattening. Quantitative
      analysis in neonatal cardiomyocytes indicated that the levels of accumulation of
      the different isoactins are very similar and cannot be responsible for the
      observed isoproteins-specific effects. Structural analysis revealed a remodeling
      of the cytoarchitecture including a specific alteration of sarcomeric
      organization; proteins constituting the sarcomeric thin filaments relocated to
      nonmyofibrillar sites while thick filaments and titin remained unaffected.
      Experiments with chimeric proteins strongly suggest that isoform specific
      residues in the carboxy-terminal portion of the cytoplasmic actins are
      responsible for the dominant negative effects on function and morphology.

PMID- 8557745
TI  - Synapsin I deficiency results in the structural change in the presynaptic
      terminals in the murine nervous system.
AB  - Synapsin I is one of the major synaptic vesicle-associated proteins. Previous
      experiments implicated its crucial role in synaptogenesis and transmitter
      release. To better define the role of synapsin I in vivo, we used gene targeting
      to disrupt the murine synapsin I gene. Mutant mice lacking synapsin I appeared to
      develop normally and did not have gross anatomical abnormalities. However, when
      we examined the presynaptic structure of the hippocampal CA3 field in detail, we
      found that the sizes of mossy fiber giant terminals were significantly smaller,
      the number of synaptic vesicles became reduced, and the presynaptic structures
      altered, although the mossy fiber long-term potentiation remained intact. These
      results suggest significant contribution of synapsin I to the formation and
      maintenance of the presynaptic structure.

PMID- 8557744
TI  - A highly divergent gamma-tubulin gene is essential for cell growth and proper
      microtubule organization in Saccharomyces cerevisiae.
AB  - A Saccharomyces cerevisiae gamma-tubulin-related gene, TUB4, has been
      characterized. The predicted amino acid sequence of the Tub4 protein (Tub4p) is
      29-38% identical to members of the gamma-tubulin family. Indirect
      immunofluorescence experiments using a strain containing an epitope-tagged Tub4p
      indicate that Tub4p resides at the spindle pole body throughout the yeast cell
      cycle. Deletion of the TUB4 gene indicates that Tub4p is essential for yeast cell
      growth. Tub4p-depleted cells arrest during nuclear division; most arrested cells
      contain a large bud, replicated DNA, and a single nucleus. Immunofluorescence and
      nuclear staining experiments indicate that cells depleted of Tub4p contain
      defects in the organization of both cytoplasmic and nuclear microtubule arrays;
      such cells exhibit nuclear migration failure, defects in spindle formation,
      and/or aberrantly long cytoplasmic microtubule arrays. These data indicate that
      the S. cerevisiae gamma-tubulin protein is an important SPB component that
      organizes both cytoplasmic and nuclear microtubule arrays.

PMID- 8557746
TI  - Structure of synaptogyrin (p29) defines novel synaptic vesicle protein.
AB  - Synaptogyrin (p29) is a synaptic vesicle protein that is uniformly distributed in
      the nervous system (Baumert et al., 1990). We have cloned and sequenced the cDNA
      encoding synaptogyrin, and the sequence predicts a protein with a molecular mass
      of 25,900 D with four membrane-spanning domains. The topology of the protein was
      confirmed by limited proteolysis using domain-specific antibodies. Database
      searches revealed several cDNA sequences coding polypeptides with sequence
      identities ranging from 32 to 46%, suggesting that synaptogyrin is a member of a
      multigene family. When the synaptogyrin cDNA is expressed in COS cells, the
      generated protein is indistinguishable from native synaptogyrin. To study
      intracellular sorting, synaptogyrin was expressed in CHO cells that revealed a
      punctate staining that was very similar to that of synaptophysin and endogenously
      expressed cellubrevin. Significant overlap with transferrin staining was also
      observed, suggesting that synaptogyrin is targeted to a recycling compartment
      involved in membrane traffic to and from the plasma membrane.

PMID- 8557747
TI  - Endocytic depletion of L-MAG from CNS myelin in quaking mice.
AB  - Quaking is an autosomal recessive hypo/dysmyelinating mutant mouse which has a 1
      Mbp deletion on chromosome 17. The mutation exhibits pleiotrophy and does not
      include genes encoding characterized myelin proteins. The levels of the 67-kD
      isoform of the myelin-associated glycoprotein (S-MAG) relative to those of the 72
      kD isoform (L-MAG) are increased in the quaking CNS, but not in other
      dysmyelinating mutants. Abnormal expression of MAG isoforms in quaking may result
      from altered transcription of the MAG gene or from abnormal sorting, transport,
      or targeting of L-MAG or S-MAG. To test these hypotheses, we have determined the
      distribution of L-MAG and S-MAG in cervical spinal cord of 7-, 14-, 21-, 28-, and
      35-d-old quaking mice. In 7-d-old quaking and control spinal cord, L- and S-MAG
      was detectable in periaxonal regions of myelinated fibers and in the perinuclear
      cytoplasm of oligodendrocytes. Between 7 and 35 d, L-MAG was removed from the
      periaxonal membrane of quaking but not control mice. Compared to control mice, a
      significant increase in MAG labeling of endosomes occurred within oligodendrocyte
      cytoplasm of 35-d-old quaking mice. S-MAG remained in periaxonal membranes of
      both quaking and control mice. Analysis of the cytoplasmic domain of L-MAG
      identifies amino acid motifs at tyrosine 35 and tyrosine 65 which meet the
      criteria for "tyrosine internalization signals" that direct transmembrane
      glycoproteins into the endocytic pathway. These results establish that L-MAG is
      selectively removed from the periaxonal membrane of CNS-myelinated fibers by
      receptor-mediated endocytosis. The loss of L-MAG from quaking periaxonal
      membranes results from increased endocytosis of L-MAG and possibly a decrease in
      L-MAG production.

PMID- 8557748
TI  - A neuron-specific isoform of brain ankyrin, 440-kD ankyrinB, is targeted to the
      axons of rat cerebellar neurons.
AB  - Two isoforms of brain ankyrin, 440- and 220- kD ankyrinB, are generated from the
      same gene by alternative splicing of pre-mRNA. The larger isoform shares the same
      NH2-terminal and COOH-terminal domains to the smaller isoform and contains, in
      addition, a unique inserted domain of about 220-kD in size (Kunimoto, M., E.
      Otto, and V. Bennett. 1991. J. Cell Biol. 115:1319-1331). Both Isoforms were
      expressed in primary cerebellar cells in a manner similar to that in vivo; the
      larger isoform appeared first when axogenesis is actively conducted and the
      smaller isoform came up later. 440-kD ankyrinB was localized in the axons of
      cerebellar neurons both in vivo and in vitro using an antibody raised against the
      insert region, while 220-kD isoform was rather localized in the cell bodies and
      dendrites of neurons by a specific antibody prepared using a synthetic peptide
      corresponding to the splice site as antigen. Astroglia cells also expressed 220
      kD ankyrinB but not the 440-kD isoform. These results indicate that 440-kD
      ankyrinB is a neuron-specific isoform targeted to the axons and its unique
      inserted domain is essential for the targeting.

PMID- 8557749
TI  - The tyrosine kinase substrate eps15 is constitutively associated with the plasma
      membrane adaptor AP-2.
AB  - The ubiquitous eps15 protein was initially described as a substrate of the EGF
      receptor kinase. Its functions are not yet delineated and this work provides
      evidence for its possible role in endocytosis. A novel anti-eps15 antibody, 6G4,
      coimmunoprecipitated proteins of molecular mass 102 kD. In human cells, these
      proteins were identified as the alpha- and beta-adaptins of the AP-2 complex on
      the basis of their NH2-terminal sequence and their immunoreactivity with anti
      alpha- and anti-beta-adaptin antibodies but not with anti-gamma-adaptin antibody.
      In addition, the anti-eps15 antibody coimmunoprecipitated metabolically labeled
      polypeptides with molecular mass of 50 and 17 kD, comparable to those of the two
      other components of the AP-2 complex, mu2 and sigma 2. Constitutive association
      of eps15 with AP-2 was confirmed by two sets of experiments. First, eps15 was
      detected in immunoprecipitates of anti-alpha- and anti-beta-adaptin antibodies.
      Second, alpha- and beta- but not gamma-adaptins were precipitated by a
      glutathione-S-transferase eps15 fusion protein. The association of eps15 with AP
      2 was ubiquitous and conserved between species, since it was observed in human
      lymphocytes and epithelial cells and in murine NIH3T3 fibroblasts. Our results
      are in keeping with a recent study showing homology between the NH2-terminal
      domains of eps15 and the product of the gene END3, involved in clathrin-mediated
      endocytosis of the pheromone alpha factor in Saccharomyces cerevisiae, and
      suggest a possible role for eps15 in clathrin-mediated endocytosis in mammals.

PMID- 8557750
TI  - V-src kinase shifts the cadherin-based cell adhesion from the strong to the weak
      state and beta catenin is not required for the shift.
AB  - The elevation of tyrosine phosphorylation level is thought to induce the
      dysfunction of cadherin through the tyrosine phosphorylation of beta catenin. We
      evaluated this assumption using two cell lines. First, using temperature
      sensitive v-src-transfected MDCK cells, we analyzed the modulation of cadherin
      based cell adhesion by tyrosine phosphorylation. Cell aggregation and
      dissociation assays at nonpermissive and permissive temperatures indicated that
      elevation of the tyrosine phosphorylation does not totally affect the cell
      adhesion ability of cadherin but shifts it from a strong to a weak state. The
      tyrosine phosphorylation levels of beta catenin, ZO-1, ERM
      (ezrin/radixin/moesin), but not alpha catenin, vinculin, and alpha-actinin, were
      elevated in the weak state. To evaluate the involvement of the tyrosine
      phosphorylation of beta catenin in this shift of cadherin-based cell adhesion, we
      introduced v-src kinase into L fibroblasts expressing the cadherin-alpha catenin
      fusion protein, in which beta catenin is not involved in cell adhesion. The
      introduction of v-src kinase in these cells shifted their adhesion from a strong
      to a weak state. These findings indicated that the tyrosine phosphorylation of
      beta catenin is not required for the strong-to-weak state shift of cadherin-based
      cell adhesion, but that the tyrosine phosphorylation of other junctional
      proteins, ERM, ZO-1 or unidentified proteins is involved.

PMID- 8557751
TI  - Targeted disruption of CD44 in MDAY-D2 lymphosarcoma cells has no effect on
      subcutaneous growth or metastatic capacity.
AB  - CD44 splice variants have been shown to be involved in metastasis of carcinomas.
      In addition, the standard form of CD44 has been implicated in metastasis,
      particularly of melanomas and lymphomas. To investigate this, we have generated a
      CD44-negative mutant of the highly metastatic murine MDAY-D2 lymphosarcoma. The
      two CD44 alleles of this diploid cell line were sequentially disrupted by
      homologous recombination, using isogenic CD44 genomic constructs interrupted by a
      neomycin or hygromycin resistance-conferring gene. The resulting double knockout
      (DKO) cells had completely lost the capacity to bind to immobilized hyaluronic
      acid, but did not differ from MDAY-D2 cells in integrin expression or in vitro
      growth. Subcutaneous (s.c.) growth potential and metastatic capacity of MDAY-D2
      and DKO cells were assessed by s.c. and i.v. injection of the lowest cell dose
      (10(3) or 10(4), respectively) that gave rise to tumor formation by MDAY-D2 cells
      in approximately 100% of the mice. Quite unexpectedly, we observed no difference
      at all in either s.c. growth rate or local invasion into surrounding tissues
      between MDAY-D2 cells and the CD44-negative DKO cells. Also hematogenous
      metastasis formation upon i.v. injection was similar: both parental and DKO cells
      metastasized extensively to the spleen, liver, and bone marrow. We conclude that,
      at least for these MDAY-D2 lymphosarcoma cells, the standard form of CD44 is
      dispensable for tumor growth and metastasis. Our results show that targeted
      disruption of genes in tumor cells is a feasible approach to study their role in
      tumorigenesis and metastasis.

PMID- 8557752
TI  - The assembly of integrin adhesion complexes requires both extracellular matrix
      and intracellular rho/rac GTPases.
AB  - Interaction of cells with extracellular matrix via integrin adhesion receptors
      plays an important role in a wide range of cellular: functions, for example cell
      growth, movement, and differentiation. Upon interaction with substrate, integrins
      cluster and associate with a variety of cytoplasmic proteins to form focal
      complexes and with the actin cytoskeleton. Although the intracellular signals
      induced by integrins are at present undefined, it is thought that they are
      mediated by proteins recruited to the focal complexes. It has been suggested, for
      example, that after recruitment to focal adhesions p125FAK can activate the
      ERK1/2 MAP kinase cascade. We have previously reported that members of the rho
      family of small GTPases can trigger the assembly of focal complexes when
      activated in cells. Using microinjection techniques, we have now examined the
      role of the extracellular matrix and of the two GTP-binding proteins, rac and
      rho, in the assembly of integrin complexes in both mouse and human fibroblasts.
      We find that the interaction of integrins with extracellular matrix alone is not
      sufficient to induce integrin clustering and focal complex formation. Similarly,
      activation of rho or rac by extracellular growth factors does not lead to focal
      complex formation in the absence of matrix. Focal complexes are only assembled in
      the presence of both matrix and functionally active members of the rho family. In
      agreement with this, the interaction of integrins with matrix in the absence of
      rho/rac activity is unable to activate the ERK1/2 kinases in Swiss 3T3 cells. In
      fact, ERK1/2 can be activated fully by growth factors in the absence of matrix
      and it seems unlikely, therefore, that the adhesion dependence of fibroblast
      growth is mediated through the ras/MAP kinase pathway. We conclude that
      extracellular matrix is not sufficient to trigger focal complex assembly and
      subsequent integrin-dependent signal transduction in the absence of functionally
      active members of the rho family of GTPases.

PMID- 8557753
TI  - A role for phosphatidylinositol 3-kinase in the regulation of beta 1 integrin
      activity by the CD2 antigen.
AB  - The rapid and reversible upregulation of the functional activity of integrin
      receptors on T lymphocytes is a vital step in the adhesive interactions that
      occur during successful T cell recognition of foreign antigen and
      transendothelial migration. Although the ligation of several different cell
      surface receptors, including the antigen-specific CD3/T cell receptor complex,
      the CD2, CD7, and CD28 antigens, as well as several chemokine receptors, has been
      shown to rapidly upregulate integrin function, the intracellular signaling events
      that initiate this increase in adhesion remain poorly defined. In this study, we
      have used DNA-mediated gene transfer to explore the role of phosphatidylinositol
      3-kinase (PI 3-K) in the upregulation of beta 1 integrin functional activity
      mediated by the CD2 antigen. CD2 was expressed in the myelomonocytic cell line
      HL60, which expresses beta 1 integrins that mediate adhesion to fibronectin and
      VCAM-1 in an activation-dependent manner. Antibody stimulation of CD2 expressed
      on HL60 transfectants resulted within minutes in increased beta 1-mediated
      adhesion to fibronectin and VCAM-1 at levels comparable to that obtained upon
      stimulation with the phorbol ester PMA. A role for PI 3-K in CD2-mediated
      increases in beta 1 integrin function is suggested by: (a) the ability of the PI
      3-K inhibitor wortmannin to completely inhibit CD2-induced increases in beta 1
      integrin activity; (b) the association of PI 3-K with CD2; and (c) induced PI 3-K
      activity upon CD2 stimulation. The mode of association of PI 3-K with CD2 is not
      mediated by tyrosine phosphorylation-dependent binding of PI 3-K via SH2 domains,
      since: (a) PI 3-K is associated with CD2 in unstimulated cells; (b) CD2
      stimulation fails to increase the amount of associated PI 3-K; and (c) the CD2
      cytoplasmic domain lacks tyrosine residues. A role for both protein kinase C and
      cytoskeletal rearrangements in CD2 regulation of integrin activity is also
      suggested, since a PKC inhibitor partially inhibits CD2-induced increases in beta
      1 integrin function, and CD2 stimulation increases F-actin content in a
      wortmannin-sensitive manner. Analysis of human peripheral T cells indicated that
      CD2 stimulation also results in PI 3-K-dependent upregulation of beta 1 integrin
      activity. Thus, these results demonstrate that CD2 can function as an adhesion
      regulator in the absence of expression of the CD3/T cell receptor complex; and
      directly implicate PI 3-K as a critical intracellular mediator involved in the
      regulation of beta 1 integrin functional activity by the CD2 antigen.

PMID- 8557754
TI  - The L1 adhesion molecule is a cellular ligand for VLA-5.
AB  - The L1 adhesion molecule is a member of the immunoglobulin superfamily shared by
      neural and immune cells. In the nervous system L1 can mediate cell binding by a
      homophilic mechanism. To analyze its function on leukocytes we studied whether L1
      could interact with integrins. Here we demonstrate that VLA-5, an RGD-specific
      fibronectin receptor on a wide variety of cell types, can bind to murine L1.
      Mouse ESb-MP cells expressing VLA-5 and L1 could be induced to aggregate in the
      presence of specific mAbs to CD24 (heat-stable antigen), a highly and
      heterogeneously glycosylated glycophosphatidylinositol-linked differentiation
      antigen of hematopoietic and neural cells. The aggregation was blocked by both
      mAbs to L1 and VLA-5, respectively. Aggregation was blocked also by a synthetic
      RGD-containing peptide derived from the Ig-domain VI of the L1 protein. ESb-MP
      subclones with low L1 expression could not aggregate. In heterotypic binding
      assays mouse bone marrow cells could adhere in an L1-dependent fashion to
      platelets that expressed VLA-5. Also purified L1 coated to polystyrene beads
      could bind to platelets. The binding of L1-beads was again inhibited by mAbs to
      L1 and VLA-5, by soluble L1 and the L1-RGD peptide in a dose-dependent manner.
      Thymocytes or human Nalm-6 tumor cells expressing VLA-5 could adhere to affinity
      purified L1 and to the L1-derived RGD-containing peptide coated to glass slides.
      The adhesion was strongly enhanced in the presence of Mn(2+)-ions and blocked by
      mAbs to VLA-5. We also demonstrate a direct L1-VLA-5 protein interaction. Our
      results suggest a novel binding pathway, in which the VLA-5 integrin binds to L1
      on adjacent cells. Given its rapid downregulation on lymphocytes after induction
      of cell proliferation, L1 may be important in integrin-mediated and activation
      regulated cell-cell interactions.

PMID- 8557755
TI  - P-selectin must extend a sufficient length from the plasma membrane to mediate
      rolling of neutrophils.
AB  - Under physiological shear stress, neutrophils roll on P-selectin on activated
      endothelial cells or platelets through interactions with P-selectin glycoprotein
      ligand-1 (PSGL-1). Both P-selectin and PSGL-1 are extended molecules. Human P
      selectin contains an NH2-terminal lectin domain, an EGF domain, nine consensus
      repeats (CRs), a transmembrane domain, and a cytoplasmic tail. To determine
      whether the length of P-selectin affected its interactions with PSGL-1, we
      examined the adhesion of neutrophils to CHO cells expressing membrane-anchored P
      selectin constructs in which various numbers of CRs were deleted. Under static
      conditions, neutrophils attached equivalently to wild-type P-selectin and to
      constructs containing from 2-6 CRs. Under shear stress, neutrophils attached
      equivalently to wild-type and 6 CR P-selectin and nearly as well to 5 CR P
      selectin. However, fewer neutrophils attached to the 4 CR construct, and those
      that did attach rolled faster and were more readily detached by increasing shear
      stress. Flowing neutrophils failed to attach to the 3 CR and 2 CR constructs.
      Neutrophils attached and rolled more efficiently on 4 CR P-selectin expressed on
      glycosylation-defective Lec8 CHO cells, which have less glycocalyx. We conclude
      that P-selectin must project its lectin domain well above the membrane to mediate
      optimal attachment of neutrophils under shear forces. The length of P-selectin
      may: (a) facilitate interactions with PSGL-1 on flowing neutrophils, and (b)
      increase the intermembrane distance where specific bonds form, minimizing
      contacts between the glycocalyces that result in cell-cell repulsion.

PMID- 8557756
TI  - Collagen and collagenase gene expression in three-dimensional collagen lattices
      are differentially regulated by alpha 1 beta 1 and alpha 2 beta 1 integrins.
AB  - The reorganization of extracellular matrix (ECM) is an important function in many
      biological and pathophysiological processes. Culture of fibroblasts in a three
      dimensional collagenous environment represents a suitable system to study the
      underlying mechanisms resulting from cell-ECM interaction, which leads to
      reprogramming of fibroblast biosynthetic capacity. The aim of this study was to
      identify receptors that transduce ECM signals into cellular events, resulting in
      reprogramming of connective tissue metabolism. Our data demonstrate that in human
      skin fibroblasts alpha 1 beta 1 and alpha 2 beta 1 integrins are the major
      receptors responsible for regulating ECM remodeling: alpha 1 beta 1 mediates the
      signals inducing downregulation of collagen gene expression, whereas the alpha 2
      beta 1 integrin mediates induction of collagenase (MMP-1). Applying mAb directed
      against different integrin subunits resulted in triggering the heterodimeric
      receptors and enhancing the normal biochemical response to receptor ligation.
      Different signal transduction inhibitors were tested for their influence on gel
      contraction, expression of alpha 1(I) collagen and MMP-1 in fibroblasts within
      collagen gels. Ortho-vanadate and herbimycin A displayed no significant effect on
      any of these three processes. In contrast, genistein reduced lattice contraction,
      and completely inhibited induction of MMP-1, whereas type I collagen down
      regulation was unaltered. Calphostin C inhibited only lattice contraction. Taken
      together, these data indicate a role of tyrosine-specific protein kinases in
      mediating gel contraction and induction of MMP-1, as well as an involvement of
      protein kinase C in the contraction process. The data presented here indicate
      that different signaling pathways exist leading to the three events discussed
      here, and that these pathways do not per se depend upon each other.

PMID- 8557757
TI  - C-terminal fragment of parathyroid hormone-related protein, PTHrP-(107-111),
      stimulates membrane-associated protein kinase C activity and modulates the
      proliferation of human and murine skin keratinocytes.
AB  - Low concentrations of the C-terminal parathyroid hormone-related protein (PTHrP)
      fragments, PTHrP-(107-111) and PTHrP-(107-139), stimulated membrane-associated
      protein kinase Cs (PKCs), but not adenylyl cyclase or an internal Ca2+ surge, in
      early passage human skin keratinocytes and BALB/MK-2 murine skin keratinocytes.
      The fragment maximally stimulated membrane-associated PKCs in BALB/MK-2 cells at
      5 x 10(-9) to 10(-8) M. The maximally PKC-stimulating concentrations of PTHrP
      (107-111) also stopped or stimulated BALB/MK-2 keratinocyte proliferation
      depending on whether the cells were, respectively, cycling or quiescent at the
      time of exposure. Thus, just one brief (30-minute) pulse of 10(-8) M PTHrP-(107
      111) stopped the proliferation of BALB/MK-2 keratinocytes for at least 5 days. On
      the other hand, daily 30-minute pulses of 10(-8) M PTHrP-(107-111) started and
      then maintained the proliferation of initially quiescent BALB/MK-2 cells.
      Similarly PTHrP-(107-111) inhibited DNA synthesis by cycling primary adult human
      keratinocytes, but it stimulated DNA synthesis by quiescent human keratinocytes.

PMID- 8557758
TI  - Basic fibroblast growth factor stimulates hepatocyte growth factor/scatter factor
      secretion by human mesenchymal cells.
AB  - Basic fibroblast growth factor (bFGF) together with other pleiotropic factors
      plays an important role in many complex physiological processes such as embryonic
      development, angiogenesis, and wound repair. Among these factors, hepatocyte
      growth factor/scatter factor (HGF/SF) which is secreted by cells of mesodermal
      origin exerts its mito- and motogenic activities on cells of epithelial and
      endothelial origin. Knowledge of the regulatory mechanisms of HGF/SF may
      contribute to the understanding of its role in physio-pathological processes. We
      observed that the secretion of HGF/SF by MRC-5 cells and by other fibroblast
      derived cell cultures in conditioned media was enhanced by exposure to bFGF.
      HGF/SF was measured by the scatter assay, a bioassay for cell motility, and was
      further characterized by Western blot analysis with anti-HGF/SF antibodies.
      Exposure of MRC-5 cultures to 10 ng/ml of bFGF resulted already 6 h posttreatment
      in a threefold higher amount of scatter factor secreted into the medium as
      compared to untreated cultures. HGF/SF secretion was sustained after bFGF
      treatment for the following 72 h when increased amounts of HGF/SF were detected
      both in conditioned media as well as associated to the extracellular matrix. The
      secretion of HGF/SF in cell supernatants increased dose dependently upon
      treatment with bFGF starting from basal levels of 6 U/ml and reaching 27 U/ml at
      30 ng/ml bFGF, plateauing thereafter. Upregulation of HGF/SF by IL-1, already
      described by others, was confirmed in this study. Based on our findings an
      articulated interaction can be speculated for bFGF, HGF/SF, and IL-1, e.g., in
      tissue regeneration during inflammatory processes or in wound healing.

PMID- 8557759
TI  - Thrombin stimulation of matrix fibronectin.
AB  - Trypsin, thrombin, and peptide analogues of the new amino terminus of the
      proteolyzed thrombin receptor, SFLLRN and SFLLRNPNDKYEPF, stimulated embryonic
      fibroblasts cultured as 3-dimensional tissue-like aggregates to elaborate a
      fibronectin-rich extracellular matrix. Enzymatically inactive thrombin and the
      control peptide FLLRN failed to stimulate matrix production. The induction of
      cell proliferation correlated with production of the fibronectin matrix. The
      regions of active cell proliferation in the fibroblast aggregates co-localized
      with the matrix and peptide analogues of the RGD cell-adhesion site of
      fibronectin reversibly inhibited the accumulation of the fibronectin matrix and
      the stimulation of cell proliferation by SFLLRN. Two different preparations of
      the fibronectin matrix stimulated cell proliferation in aggregates cultured in
      growth factor-free medium. We suggest that the stimulation of matrix production
      is a necessary event for mitogenic signaling in mesenchymal tissue. The tight
      coupling between the matrigenic and mitogenic activities of growth factors was
      absent in monolayer cultures of chick embryonic fibroblasts since thrombin and
      trypsin induced proliferation of monolayer-cultured cells without inducing the
      production of a fibronectin matrix.

PMID- 8557760
TI  - Suppression of platelet-derived growth factor alpha- and beta-receptor mRNA
      levels in human fibroblasts by SV40 T/t antigen.
AB  - It is known that down-regulation of cell surface platelet-derived growth factor
      (PDGF) receptors accompanies transformation by SV40. In this work human embryonic
      lung fibroblasts were used as a model system to study the effects of SV 40 on
      PDGF receptor expression. It is shown that transformation by SV 40 early region
      leads to a total loss of PDGF alpha-receptor and partial loss of beta-receptor
      mRNA. Microinjection experiments revealed that receptor down-regulation was a
      primary effect, and not only secondary to transformation and clonal selection.
      Total loss of PDGF alpha-receptor expression requires both large T and small t,
      and down-regulation of the PDGF alpha-receptor occurs independently of p53 and Rb
      binding to large T.

PMID- 8557761
TI  - Interaction of insulin, glucocorticoids, and protein kinase C in the regulation
      of insulin-like growth factor-binding protein-1 production by H4IIE rat hepatoma
      cells.
AB  - A sensitive RIA was used to examine regulation of IGFBP-1 in H4IIE rat hepatoma
      cells. IGFBP-1 was stimulated up to tenfold by dexamethasone and corticosterone,
      and this stimulation was abolished by RU486. The effect of dexamethasone
      increased with time in culture. Phorbol 12-myristate 13-acetate (PMA) stimulated
      IGFBP-1 up to fourfold with a maximal effect in short-term culture. Dexamethasone
      and PMA were additive in stimulating IGFBP-1. Under basal conditions IGFBP-1
      production was linearly related to cell density: however, stimulation by
      dexamethasone was greatest in confluent cells, and PMA had a greater effect in
      sparse cultures. Insulin inhibited IGFBP-1 up to 80%, and this effect diminished
      with time in culture but was unaffected by cell density. Dexamethasone was
      stimulatory in the presence of a maximal inhibitory concentration of insulin, and
      insulin was inhibitory in the presence of maximal dexamethasone from 3-48 h in
      culture, regardless of cell density. PMA abolished the inhibitory action of
      insulin on IGFBP-1 secretion and mRNA expression during incubation periods of
      less than 4 h and not during longer incubations. PMA did not influence the
      stability of IGFBP-1 mRNA. We conclude that, in rat H4IIE cells, dexamethasone
      and PMA stimulate IGFBP-1 by independent mechanisms and speculate that when
      protein kinase C is activated the inhibitory action of insulin is blocked.

PMID- 8557762
TI  - Regulation by prostaglandin E2 of interleukin release by T lymphocytes in mucosa.
AB  - Regulation of immune cell activation in lymphocyte-bearing human tissues is a
      pivotal host function, and metabolites of arachidonic acid (prostaglandin E2 in
      particular) have been reported to serve this function at non-mucosal sites.
      However, it is unknown whether prostaglandin E2 is immunoregulatory for the large
      lymphocyte population in the lamina propria of intestine; whether low (nM)
      concentrations of prostaglandin E2 modulate immune responses occurring there; and
      whether adjacent inflammation per se abrogates prostaglandin E2's regulatory
      effects. To address these issues, intestine-derived lymphocytes and T hybridoma
      cells were assessed, T cell activation was monitored by release of independently
      quantitated lymphokines, and dose-response studies were performed over an 8-log
      prostaglandin E2 concentration range. IL-3 release by normal intestinal lamina
      propria mononuclear cells was reduced (up to 78%) in a dose-dependent manner by
      prostaglandin E2, when present in as low a concentration as 10(-10) M. PGE2 also
      inhibited (by > or = 60%) mucosal T lymphocytes' ability to destabilize the
      barrier function of human epithelial monolayers. Further, with an intestine
      derived T lymphocyte hybridoma cell line, a prostaglandin E2 dose-dependent
      reduction in IL-3 and IL-2 (90 and 95%, respectively) was found; this was true
      for both mitogen- and antigen-driven T cell lymphokine release. Concomitant [3H]
      thymidine uptake studies suggested this was not due to a prostaglandin E2-induced
      reduction in T cell proliferation or viability. In contrast, cells from
      chronically inflamed intestinal mucosa were substantially less sensitive to
      prostaglandin E2, e.g., high concentrations (10(-6) M) of prostaglandin E2
      inhibited IL-3 release by only 41%. We conclude that prostaglandin E2 in nM
      concentrations is an important modulator of cytokine release from T lymphocytes
      derived from the gastrointestinal tract, and it may play a central role in
      regulation of lamina propria immunocyte populations residing there.

PMID- 8557763
TI  - Ex vivo analysis of leukocyte hydrogen peroxide production using a bi-plate model
      in mice.
AB  - Implantation of artificial materials is followed by inflammation and wound
      healing, where phagocytic cells play an important role. The mechanisms whereby
      the implant surface may elicit and modulate leukocyte functions in vivo are not
      understood, partly due to the technical difficulties of examining the local
      inflammatory events in vicinity of the material-tissue interface with
      conventional biochemical and immunological techniques. In the present study a
      newly developed biplate implant was inserted subcutaneously in the mouse.
      Leukocytes from the local inflammatory exudate and leukocytes associated to the
      surface of the implants were retrieved after 1 and 6 days and separately assayed
      with respect to hydrogen peroxide (H2O2) production ex vivo. Implantation caused
      a local accumulation of predominantly mononuclear cells in the surrounding
      subcutaneous tissue. The H2O2 production was found to be low in both the
      subcutaneous exudate and the implant-associated leukocytes, irrespective of
      implant material and implantation times. However, ex vivo-stimulation with
      phorbol myristate acetate (PMA) caused an enhanced H2O2 production. These
      observations show that biplate implants do not maximally activate the oxidative
      metabolism of the recruited leukocytes. The exudate leukocytes were more
      responsive to PMA stimulation in comparison with implant-associated leukocytes,
      indicating that properties of the implant surface and possibly surface-associated
      proteins could modify the responsiveness of the phagocytic cells at the implant
      site. Our results suggest that the present biplate model may be suitable for
      further studies on local production of oxygen metabolites and function of
      leukocytes at implanted biomaterials.

PMID- 8557764
TI  - Atherogenic levels of low-density lipoprotein increase hydrogen peroxide
      generation in cultured human endothelial cells: possible mechanism of heightened
      endocytosis.
AB  - Cultured human umbilical vein endothelial cells(EC) exposed to atherogenic low
      density lipoprotein (LDL) levels have augmented reactive oxygen species
      generation. Confluent EC were incubated with 30-330 mg/dl LDL cholesterol and
      cellular hydrogen peroxide (H2O2) generation measured. EC incubated with 30 and
      90 mg/dl LDL cholesterol showed similar low level H2O2 production. In contrast,
      EC exposed to 180 and 330 mg/dl LDL cholesterol have a marked, dose-related
      elevation in H2O2 generation. Subsequent studies have explored if direct EC
      exposure to H2O2 promotes cellular functional changes similar to those induced by
      high LDL levels (> 160 mg/dl cholesterol). Confluent EC were incubated with 0.1
      10 mM H2O2 for 30 minutes and endocytosis measured and cytoskeletal structure
      examined. H2O2 exposure (0.5 and 1 mM) promoted heightened EC endocytosis, which
      similarly occurs with high LDL exposure. Likewise, cytoskeletal examination of EC
      perturbed with 1 mM H2O2 reveals structural remodeling with a marked increase in
      stress fibers, which similarly happens with high LDL levels. The above
      observations that high LDL levels cause increased EC H2O2 production, and direct
      H2O2 exposure promotes cellular functional changes similar to those induced by
      high LDL concentrations, suggest a modulatory role for reactive oxygen species.
      Thus LDL-induced reactive oxygen species generation may contribute
      mechanistically to endothelial perturbation, which has been hypothesized to be a
      major contributing factor in the pathogenesis of atherosclerosis.

PMID- 8557765
TI  - Comparative analysis of glucose and glutamine metabolism in transformed mammalian
      cell lines, insect and primary liver cells.
AB  - Glucose and glutamine metabolism in several cultured mammalian cell lines (BHK,
      CHO, and hybridoma cell lines) were investigated by correlating specific
      utilization and formation rates with specific maximum activities of regulatory
      enzymes involved in glycolysis and glutaminolysis. Results were compared with
      data from two insect cell lines and primary liver cells. Flux distribution was
      measured in a representative mammalian (BHK) and an insect (Spodoptera
      frugiperda) cell line using radioactive substrates. A high degree of similarity
      in many aspects of glucose and glutamine metabolism was observed among the
      cultured mammalian cell lines examined. Specific glucose utilization rates were
      always close to specific hexokinase activities, indicating that formation of
      glucose-6-phosphate from glucose (catalyzed by hexokinase) is the rate limiting
      step of glycolysis. No activity of the key enzymes connecting glycolysis with the
      tricarboxylic acid cycle, such as pyruvate dehydrogenase, pyruvate carboxylase,
      and phosphoenolpyruvate carboxykinase, could be detected. Flux distribution in
      BHK cells showed glycolytic rates very similar to lactate formation rates. No
      glucose- or pyruvate-derived carbon entered the tricarboxylic acid cycle,
      indicating that glucose is mainly metabolized via glycolysis and lactate
      formation. About 8% of utilized glucose was metabolized via the pentose phosphate
      shunt, while 20 to 30% of utilized glucose followed pathways other than
      glycolysis, the tricarboxylic acid cycle, or the pentose phosphate shunt. About
      18% of utilized glutamine was oxidized, consistent with the notion that glutamine
      is the major energy source for mammalian cell lines. Mammalian cells cultured in
      serum-free low-protein medium showed higher utilization rates, flux rates, and
      enzyme activities than the same cells cultured in serum-supplemented medium.
      Insect cells oxidized glucose and pyruvate in addition to glutamine. Furthermore,
      insect cells produced little or no lactate and were able to channel glycolytic
      intermediates into the tricarboxylic acid cycle. Metabolic profiles of the type
      presented here for a variety of cell lines may eventually enable one to interfere
      with the metabolic patterns of cells relevant to biotechnology, with the hope of
      improving growth rate and/or productivity.

PMID- 8557766
TI  - In vitro changes in plasma membrane heparan sulfate proteoglycans and in perlecan
      expression participate in the regulation of fibroblast growth factor 2 mitogenic
      activity.
AB  - Fibroblast growth factor 1 (FGF1) and 2 (FGF2) bind to two classes of receptors:
      the high affinity receptors, a family of four known transmembrane tyrosine
      kinases (FGF R1-R4), and the low affinity receptors, cell surface and basement
      membrane heparan sulfate proteoglycan (HSPG). During early (first and second)
      passages of retinal pigmented epithelial (RPE) cells, both FGF1 and FGF2
      exhibited low mitogenic activity, while in later (fifth to ninth) passages the
      activity of FGF1 remained constant but FGF2 activity increased two- to threefold.
      We have investigated aspects of FGF receptor interactions and the role of
      heparin/heparan sulfate which modulates FGF activity on RPE cells during in vitro
      senescence. Northern blot analysis demonstrated that FGF receptor type 1 (FGF R1)
      is the major high affinity receptor expressed in RPE cells and that its level of
      expression did not change during serially passage. Both the FGF R1 and the FGF
      low affinity receptors' binding characteristics (i.e., Kd and number of sites per
      cell) for FGF1 were unaffected by passage number, whereas the capacity of FGF2
      binding to FGF R1 and to the low affinity receptors increased by two- and
      fivefold, respectively, in late passages, although the affinities were unchanged.
      This change in the capacity of FGF2 to bind to FGF R1 and to HSPG was not due to
      a switch of the IIIc splice form of FGF R1 to the IIIb splice form since the exon
      IIIc was the most predominant splice form of FGF R1 during RPE cell cultures.
      Furthermore the ratio of the IIIb to the IIIc splice form was not modified during
      cell subcultures. In parallel in the older RPE cell passages, expression of
      perlecan, the major FGF low affinity binding site localized on the extracellular
      matrix of RPE cells, was much elevated compared to early RPE cell passages.
      Moreover, the cell surface of late passage RPE cells had 79% more HSPG than early
      passage cells. Therefore, it is suggested that the increase in the number of FGF
      low affinity receptors present on the cell surface or basement membrane could
      account for a part of the greater proliferative response of aged RPE cells to
      FGF2.

PMID- 8557767
TI  - Pro-inflammatory cytokines downregulate platelet derived growth factor-alpha
      receptor gene expression in human osteoblastic cells.
AB  - Platelet derived growth factor (PDGF) is thought to play a significant role in
      bone repair and regeneration. We previously demonstrated that PDGF-AA binding can
      be modulated by interleukin-1 (IL-1). We now report that TNF-alpha significantly
      reduces PDGF-AA binding by decreasing the number of PDGF-alpha receptor subunits
      on the surface of normal human osteoblastic cells. This inhibition is likely due
      to a decrease in synthesis of PDGF-alpha receptors since TNF-alpha causes a
      relatively rapid decrease in PDGF-alpha receptor mRNA levels as determined by
      Northern blot analysis. The physiologic importance of this inhibition is
      demonstrated by a TNF-alpha induced decrease in PDGF-AA stimulated tyrosine
      kinase activity. When saturating concentrations of TNF-alpha were used, the
      addition of IL-1 further inhibited PDGF-AA binding and further decreased surface
      expression of PDGF-alpha receptors. In contrast, other mediators such as IL-6,
      PTH, 1,25(OH)2 vit D3, hydrocortisone, PGE2, bFGF, and IGF-1 had no effect. These
      results suggest that binding to the PDGF-alpha receptor is decreased by the
      strong pro-inflammatory cytokines such as IL-1 beta and TNF-alpha rather than as
      a general response to mediators important in bone resorption or bone formation.
      TNF-alpha and IL-1 are often co-expressed during destructive inflammatory
      processes. Thus, TNF-alpha and IL-1 may work in concert to limit the response of
      osteoblastic cells to PDGF-AA during periods of osseous inflammation.

PMID- 8557768
TI  - Uncoordinated, transient mosaic patterns of intestinal hydrolase expression in
      differentiating human enterocytes.
AB  - The heterogenous expression of brush border membrane hydrolases by the human
      enterocyte-like Caco-2 cell line during morphological and functional
      differentiation in vitro was investigated at the cellular level. Indirect
      immunofluorescence revealed that the heterogeneous ("mosaic") expression of
      sucrase-isomaltase, lactase, aminopeptidase N, and alkaline phosphatase was, in
      fact, transient in nature. The labeling indexes for each hydrolase gradually
      increased during culture at postconfluence in order to reach a maximum (> or =
      90%) after 30 days, concomitant with an upregulation of their respective protein
      expression levels. In contrast, dipeptidylpeptidase IV labeling remained
      relatively constant. Backscattered electron imaging analysis in midstage (12 days
      postconfluence) monolayers demonstrated a lack of correlation between brush
      border membrane development and expression of each enzyme studied. Moreover,
      double immunostaining revealed that none of the other four hydrolases correlated
      directly with sucrase-isomaltase expression. Finally, immunodetection for the
      proliferation-associated antigen KI-67 revealed a transient mosaic pattern of
      proliferation which was inversely related to Caco-2 cell differentiation. These
      data indicate that enterocytic differentiation-related (as well as proliferation
      related) gene expression in Caco-2 cells is regulated but uncoordinated at the
      cellular level, suggesting that an overall control mechanism is lacking.

PMID- 8557769
TI  - Improved hepatocyte culture system for studying the regulation of glycogen
      synthase and the effects of diabetes.
AB  - When 3-4-week-old rats (young rats) are used as a source of hepatocytes, primary
      culture cells express the adult, differentiated, liver-specific isoform of
      glycogen synthase. Synthase enzyme protein levels are relatively stable over a 3
      day culture period in young but not in adult (> 150 g rat) hepatocyte cultures.
      Corresponding synthase enzyme activity and mRNA levels decrease over time in
      culture in adult but not in young hepatocyte cultures. Young rat hepatocytes also
      have the ability to proliferate in chemically defined medium in the absence of
      added mitogens. A diabetes-induced increase in total synthase activity has been
      demonstrated by our lab and others, using cultured hepatocytes, liver
      homogenates, and perfused livers. In the present study, utilizing synthase
      specific antibody and primary cultures of cells from young normal and alloxan
      diabetic rats, we found that greater total synthase activity in the diabetic
      cells was associated with higher levels of enzyme protein. Immuneprecipitation of
      35S methionine-labeled freshly plated cells demonstrates an increase in the rate
      of protein synthesis in diabetic as compared with normal cells. Synthase mRNA
      levels are correspondingly increased in the diabetic relative to normal cells.
      Chronic exposure of young, normal hepatocytes to increasing levels of glucose
      induces a dose-dependent increase in total synthase activity, total synthase
      protein, and synthase message levels. By comparison, cells from diabetic animals
      do not respond by any of these measures to increased glucose concentrations. We
      conclude that this defined primary culture system represents a useful model for
      investigating the regulation of hepatic glycogen synthase and the defects which
      occur as a result of diabetes.

PMID- 8557770
TI  - Persistent effects of phorbol 12-myristate 13-acetate: possible implication of
      vesicle traffic.
AB  - Relative to their normal counterparts, transformed epithelial cells have a
      distinctive and quantifiable three-dimensional shape. Biophysical and
      mathematical methods are used to distinguish these extremes in cells from two
      lines, cultured from rat liver and tracheal epithelium, respectively. Cells
      adopted a more transformed-looking configuration transiently when exposed to
      phorbol 12-myristate 13-acetate (PMA) (Plummer and Heckman, [1990] Exp. Cell
      Res., 188:66-74). The purpose of the present work was to dissect the
      physiological processes involved in the shape change. Ruffling activity, known to
      be PMA-stimulated in other cells, was investigated. Although the ruffles appeared
      less robust than normal, PMA stimulated ruffling activity over a 5 h period. The
      number of sites where ruffling was initiated declined by 5 h, however, and
      suppression was seen by 10 h. Cells from both lines adopted the transformed shape
      configuration when exposed for 2 h to monensin. When the subset of shape features
      changed by this treatment was compared with those originally changed during
      transformation, it was found that monensin-treated cells mimicked the features of
      transformed cells. Its effect on ruffling was, however, unlike PMA's. Thus, the
      phenotype was unlikely to arise from ruffling itself but might be a process
      driven by ruffling. Chloroquine also stimulated cells to assume characteristics
      of transformed cells. Since both it and monensin could interfere with endosomes
      and with the processing of endocytosed contents, this was a likely site of
      action. Experiments were done to determine whether PMA also affected the
      processing of extracellular fluids. When the accumulation of horseradish
      peroxidase (HRP) was measured, the rate was found to be higher in PMA-treated
      cells from 5 min, the earliest time assayed, onward. The results suggest that the
      transformed type of cell in these cell lines showed a constitutive dilation
      and/or reorganization of some portion of the endosomal pathway.

PMID- 8557772
TI  - Induction of transforming growth factor-beta autocrine activity by all-trans
      retinoic acid and 1 alpha,25-dihydroxyvitamin D3 in NRP-152 rat prostatic
      epithelial cells.
AB  - Retinoids and vitamin D analogues are known to inhibit the proliferation of a
      variety of cells in culture and prevent the formation of certain tumors in
      mammals. Although it is well established that these hormones control the
      transcription of many genes upon binding to and activating specific nuclear
      receptors, the mechanisms by which they prevent cancer are as yet poorly
      understood. In this study the role of the transforming growth factor-beta (TGF
      beta) growth inhibitors, in promoting the biological activities of all-trans
      retinoic acid (RA) and 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) was studied
      in NRP-152 cells, a nontumorigenic epithelial line derived from rat dorsal
      lateral prostate. Inhibition of growth by nanomolar concentrations of RA was
      associated with an increase in both mRNA and protein for all three TGF-beta
      isoforms, with greater and much earlier increases for TGF-beta s 2 and 3 (5.5 h)
      than for TGF-beta 1 (24 h). A monoclonal antibody against TGF-beta and TGF-beta 1
      latency associated peptide (LAP), both of which neutralize all three TGF-beta
      isoforms, each block the ability of RA to inhibit growth of NRP-152 cells by >
      95%. Neutralization of growth inhibition by isoform-specific antibodies suggested
      that all three TGF-beta s are involved in this effect. The ability of RA to
      upregulate fibronectin and thrombospondin expression in NRP-152 cells was also
      blocked by the monoclonal antibody. 1,25-(OH)2D3, which also induced TGF-beta s 2
      and 3 but not TGF-beta 1, and their respective mRNAs, also induced fibronectin
      and thrombospondin through induction of TGF-beta. Thus, autocrine production of
      TGF-beta s may be a significant part of the mechanisms by which RA and 1,25
      (OH)2D3 promote cellular differentiation.

PMID- 8557771
TI  - Pregnancy-stimulated growth of vascular smooth muscle cells: importance of
      protein kinase C-dependent synergy between estrogen and platelet-derived growth
      factor.
AB  - Dramatic smooth muscle cell (SMC) growth occurs in the uterine artery during
      pregnancy. The potential for pregnancy-associated growth may also exist at other
      vascular sites. We tested the hypothesis that increased growth of uterine artery
      SMC isolated from pregnant (vs. nonpregnant) guinea pigs would be detectable in
      culture, that pregnancy-associated phenotypic changes would also be found in
      nonuterine vascular cells (aortic SMC), and that the enhanced growth would be
      dependent on estrogen, peptide growth factors like platelet-derived growth factor
      (PDGF), and protein kinase C (PKC). Growth responses were measured by [3H]
      thymidine incorporation and cell counts. Uterine artery SMC from pregnant guinea
      pigs grew to a higher plateau density with serum stimulation, had increased
      spontaneous DNA synthesis and persistent growth following serum with-drawal, and
      were more responsive to 3-30 ng/ml PDGF-BB than nonpregnant cells. Aortic SMC
      from pregnant animals also grew to a higher plateau density and had enhanced
      responsiveness of PDGF-BB. This increased response to PDGF-BB by pregnant uterine
      artery and aortic SMC (40-233% increase over nonpregnant PDGF result) was
      reproduced in nonpregnant cells by pretreatment for 1-24 h with 17-beta(beta)
      estradiol (30-100 nM). Neither the pregnancy-induced difference nor the estradiol
      pretreatment was associated with increased PDGF-BB binding activity. The
      synergistic effect of 17 beta-estradiol was partially (62%) reproduced with 17
      alpha(alpha)-estradiol, an isomer which does not bind the estrogen receptor. This
      suggested that 17 beta-estradiol modulates the PDGF-BB response by both estrogen
      receptor- and nonreceptor-mediated mechanisms. To test if the estrogen effects
      were dependent on PKC, two different antagonist strategies (3 microM
      dihydrosphingosine and phorbol-ester-induced downregulation) were applied prior
      to 17 alpha- or beta-estradiol and blocked the enhanced responses to PDGF. The
      synergistic effect of 17 beta-estradiol on PDGF was then reproduced by 1 h
      pretreatment with the cell-permeable PKC activator, 10 nM PMA. We conclude that
      pregnancy stimulates increased growth of uterine and aortic SMC in vitro which is
      dependent on estrogen, PDGF, and PKC and may be important in vascular remodeling
      during pregnancy.

PMID- 8557773
TI  - Quantitative analysis of collagen gel contractile forces generated by dermal
      fibroblasts and the relationship to cell morphology.
AB  - The force generated in granulation tissue during wound contraction is thought to
      be cell mediated; however, it is unclear whether contractile forces are generated
      by fibroblast locomotion or contraction of myofibroblasts. To help clarify this
      question the force of this contraction can now be determined accurately in a
      human dermal fibroblast collagen lattice system using a novel instrument known as
      a Culture Force Monitor. Three distinct phases of contraction of such collagen
      gels could be identified over the first 24 hours. Most of the force generated by
      human dermal fibroblasts was produced during the first stage in parallel with
      cell attachment and associated changes in cell shape, and the appearance of cell
      processes. During this initial 24 hours no evidence could be found for the
      presence of myofibroblasts, but stereoscopic and electron microscopic analysis at
      a range of time points indicated that migratory fibroblasts were present in the
      system. Comparison of the contraction profiles of cells extracted from other
      tissues (tendon and articular cartilage), and extracted by different means from
      the same tissue specimen, indicated that different populations of fibroblasts can
      be distinguished on the basis of their pattern of contractions. It would seem
      that most of the force generated in this model is a result of fibroblast
      attachment and movement within the collagen lattice. Furthermore, different
      groups of fibroblasts, even within the same tissue, may vary in their contraction
      (hence locomotory) activity.

PMID- 8557774
TI  - Isolation of a polyamine transport deficient cell line from the human non-small
      cell lung carcinoma line NCI H157.
AB  - In an effort to study the mechanism underlying the observed phenotype-specific
      response of human lung cancer cell lines to a polyamine analogue, N1,N12
      bis(ethyl)spermine(BESpm), we have isolated a BESpm resistant cell line from the
      BESpm-sensitive large cell lung carcinoma line NCI H157. The mutant line exhibits
      identical growth rates in the presence or absence of the analogue. However, the
      overall growth of mutant cells reaches stationary phase earlier than that of the
      parental cells. In contrast to the parental cells, where a superinduction of
      spermidine/spermine N1-acetyltransferase (SSAT) is associated with BESpm
      toxicity, treatment of this resistant line with BESpm did not induce SSAT mRNA or
      enzyme activity. BESpm treatment was not effective in depleting the intracellular
      polyamine pools and very low intracellular BESpm levels were detected. This BESpm
      resistance is not mediated by multidrug resistance (MDR) protein, since these
      cells maintain their sensitivity to the antineoplastic agent adriamycin.
      Treatment of these cells with methylglyoxal bis(guanylhydrazone) (MGBG), an
      AdoMetDC inhibitor which enters cell using polyamine transport system, shows no
      inhibition of cell growth. Our data suggest that these mutant cells are deficient
      in polyamine transport. Consistent with this hypothesis, exogenous polyamines did
      not prevent difluoromethylornithine (DFMO) induced growth inhibition in the
      mutant cells.

PMID- 8557775
TI  - Maitotoxin, a calcium channel activator, inhibits cell cycle progression through
      the G1/S and G2/M transitions and prevents CDC2 kinase activation in GH4C1 cells.
AB  - Calcium regulates progression through several checkpoints in the cell cycle,
      including the G1/S-phase transition, G2/M-phase transition, and exit from
      mitosis. In the GH4C1 rat pituitary cell line, calcium mobilizing polypeptides
      and calcium channel activation inhibit cell proliferation. This report examines
      the effects of maitotoxin (MTX), an activator of type L voltage-dependent calcium
      channels (L-VDCC), on calcium influx and cell cycle progression in GH4C1 cells.
      MTX causes both a block from G1 to S-phase and a concentration-dependent
      accumulation of cells in G2+M. MTX does not increase the mitotic index; thus,
      sustained calcium channel activation by MTX results in an accumulation of cells
      in G2. In order to temporally localize the MTX-induced G2 block relative to cell
      cycle regulatory events at the G2/M transition, we assessed the relative activity
      of two cell cycle regulatory protein kinases, CDC2 and CDK2, in MTX-treated
      cells. CDC2-specific histone kinase activity in MTX-treated cells is lower than
      either in cells blocked in mitosis with the microtubule destabilizing agent
      demecolcine or in randomly cycling cells. In contrast, the activity of CDK2 is
      highest in MTX-treated cells, consistent with a G2 block prior to CDC2
      activation. Together, these results implicate with a G2 block prior to CDC2
      activation. Together, these results implicate calcium as an intracellular signal
      required for progression through G2 phase of the cell cycle prior to CDC2 kinase
      activation.

PMID- 8557776
TI  - Nucleotide receptor P2u partially mediates ATP-induced cell cycle progression of
      aortic smooth muscle cells.
AB  - mRNA of the P2u purinoceptor (or nucleotide receptor) is detected both by
      polymerase chain reaction or Northern blot analyses in cultured aortic smooth
      muscle cells. When added to the culture medium of these cells, UTP, a specific
      ligand of the P2u receptor, induces an increased expression of both immediate
      early and delayed-early cell cycle-dependent genes. This induction demonstrates
      similar features (kinetics, concentration dependence) to those obtained after
      stimulation of aortic smooth cells by exogenous ATP, a common ligand for most P2
      purinoceptors. In contrast, 2-methylthioATP, a preferential ligand for P2y
      purinoceptors, induces only a significant increase of immediate-early genes but
      not of delayed-early genes. Moreover, the 2-methylthioATP-induced responses (c
      fos mRNA increase, free intracellular calcium transient) are lower than those
      induced by ATP or UTP and are complementary to those of UTP. These results
      demonstrate that functional P2u receptors are present on cultured aortic smooth
      muscle cells and suggest that the bulk of responses induced by extracellular ATP
      on cell cycle progression are mediated via P2u purinoceptors, a hypothesis
      confirmed by cytofluorometric studies. Since some ATP- or UTP-induced genes code
      for chemotactic proteins (monocyte chemoattractant protein-1 and osteopontin),
      this study suggests that these nucleotides may contribute to vascular or blood
      cell migration and proliferation and consequently to the genesis of arterial
      diseases.

PMID- 8557777
TI  - Okadaic acid gives concentration-dependent reciprocal effects on the fluid phase
      endocytosis activated by Ca2+ and phorbol 12-myristate 13-acetate.
AB  - Incubation of a human fibrosarcoma cell line HT-1080 in increasing concentration
      of Ca2+ was found to enhance endocytic internalization of a fluid phase marker,
      horseradish peroxidase. At 16.8 mM Ca2+, generation of the effect required
      incubation for more than 45 min. The effect was reversed by removal of the excess
      ion for 30 min. Monitoring the intracellular concentration showed that the
      incubation induced a transient large Ca2+ influx followed by a recovery to 230 +/
      50 nM instead of the normal level of 83 +/- 5 nM. The activation was not
      inhibited by inhibitors of protein kinases nor a cAMP antagonist. In contrast,
      the effect was prevented by okadaic acid (OKA) at 100 nM without detectable
      effect on the basal activity. Fluid phase uptake by HT-1080 cells was also
      enhanced by phorbol 12-myristate 13-acetate (PMA). In contrast to the case with
      Ca2+, OKA at 100 nM did not prevent the PMA effect but further enhanced the
      endocytosis. The effect of OKA was concentration-dependent, as the reagent at 1
      microM inhibited not only both the activation but also the basal activity. In
      Ca(2+)- or PMA-stimulated cells, FITC-dextran was delivered to endosomes that had
      been labeled with TRITC-transferrin. In contrast, following treatment with a
      combination of PMA and 100 mM OKA, fluid phase was internalized in vesicular
      compartments devoid of transferrin labeling. These results suggest that, through
      differential modifications of protein phosphorylation, endocytosis can be
      enhanced distinctively either by employing conventional receptor-bearing
      compartments or generating a new endosomal population.

PMID- 8557778
TI  - Functional characterization of prostaglandin E2 inducible osteogenic colony
      forming units in cultures of cells isolated from the neonatal rat calvarium.
AB  - Prostaglandin E2 (PGE2) increases the number of mineralized nodules that form in
      cultures of rat calvarial (RC) cells. The purpose of our study was to
      characterize PGE2-inducible osteogenic colony forming units (CFU-Os) by
      determining their number, the cell populations from which they were released,
      their specific responsive period to PGE2, and their proliferating and
      differentiating characteristics under the stimulation of PGE2. Limiting dilution
      analysis was used to determine the number of PGE2-inducible CFU-Os. Sequential
      digestion of intact rat parietal bones with collagenase isolated 5 subpopulations
      of RC cells that were used to estimate the cell populations where PGE2-inducible
      CFU-Os resided. The responsive period of PGE2-inducible CFU-Os to PGE2 was
      evaluated by treating cultures of mixed RC cells for all possible combinations of
      days 1-10, 11-20, and 21-30. PGE2 effects on proliferation and differentiation of
      CFU-Os were evaluated by comparing the DNA synthesis and AP activity in
      subpopulations I and IV on days 3, 6, and 9. Results showed: (1) PGE2-inducible
      CFU-Os represent 0.27% of cells in the mixed RC population, (2) the majority of
      determined and PGE2-inducible CFU-Os were found in the subpopulations released
      during the 60-100 min digestion periods, (3) the response of PGE2-inducible CFU
      Os is limited to the first 10 days of culture, and (4) PGE2-stimulated nodule
      formation is associated with an early increase in DNA synthesis and a sustained
      increase in alkaline phosphatase activity. We conclude that, functionally, PGE2
      inducible CFU-Os are slowly proliferating AP negative cells primarily found in
      the subpopulations III-V. PGE2 stimulates them to proliferate and become AP+, and
      function as determined CFU-Os to form mineralized nodules in vitro.

PMID- 8557779
TI  - Effect of retinoic acid in combination with platelet-derived growth factor-BB or
      transforming growth factor-beta on tissue inhibitor of metalloproteinases and
      collagenase secretion from human skin and synovial fibroblasts.
AB  - This report shows for the first time that platelet-derived growth factor-BB (PDGF
      BB) and transforming growth factor-beta (TGF-beta) can interact in a synergistic
      manner with retinoic acid to stimulate the production of tissue inhibitor of
      metalloproteinases (TIMP) from human skin and synovial fibroblasts. When cells
      are treated with 1, 10, and 100 ng/ml of either of these growth factors in
      combination with 10(-5) M retinoic acid, this results in a dose-dependent
      synergistic induction of TIMP protein secretion which is greater than the
      additive effect of the agents by up to fourfold. These responses can be inhibited
      by the presence of specific neutralising antibodies to the growth factors,
      demonstrating that they are not the result of an experimental artefact such as
      contamination with bacterial endotoxin. The mechanisms of these synergistic
      responses may involve the induction of receptors for retinoic acid, PDGF, or TGF
      beta or may result from synergistic effects on TIMP gene transcription. We have
      also found that retinoic acid potently down-regulates PDGF-BB-stimulated
      collagenase in both types of fibroblast and that the effect of PDGF-BB alone on
      collagenase secretion from skin fibroblasts is biphasic. Finally, this study
      reports that retinoic acid and TGF-beta do not act in an additive fashion to
      inhibit the production of collagenase from skin fibroblasts.

PMID- 8557780
TI  - Expression of parathyroid hormone-related protein in cells of osteoblast lineage.
AB  - The expression of parathyroid hormone-related protein (PTHrP) was studied in a
      range of cell cultures representative of the osteoblast lineage and in rat
      calvarial sections. Primary newborn rat calvarial cells, a rat preosteoblastic
      cell line (UMR 201), a mouse stromal cell line (ST 2), a mouse calvaria-derived
      osteoblastic cell line (KS 4), and rat osteosarcoma cell lines (UMR 106-01 and 
      06), all expressed PTHrP when examined by reverse transcription polymerase chain
      reaction (RT-PCR). Using a radioimmunoassay we also demonstrated PTHrP in the
      conditioned medium of the cultured cells, with the exception of UMR 106-01 and 
      06 cells. Treatment of UMR 201 cells with all-trans-retinoic acid which induces
      them to acquire a more differentiated phenotype, also led to a time-dependent
      decrease in PTHrP mRNA levels as determined by RT-PCR, Northern blot analysis,
      and in situ hybridization. Decreased PTHrP levels in the conditioned medium of
      the treated cells was also observed. These results suggested that PTHrP
      production might be greater in less mature osteoblasts. Examination of the
      populations obtained from newborn rat calvariae by sequential collagenase
      digestion revealed that the early digests exhibited low ALP activity, low
      expression of PTH/PTHrP receptor mRNA, and no adenylate cyclase response to
      PTHrP(1-34). These populations showed the highest level of mRNA and production of
      PTHrP. Cells from later digests, the "osteoblast-rich" populations, had reduced
      PTHrP expression. Immunohistochemistry and in situ hybridization in sections of
      newborn rat calvariae showed PTHrP expression in cuboidal osteoblasts located
      adjacent to bone and in spindle-shaped cells in the periosteal region. It is
      concluded that PTHrP is produced by cells of the osteoblast lineage, supporting
      the hypothesis that PTHrP may function physiologically as a paracrine factor in
      bone.

PMID- 8557781
TI  - Some historical comments on quarantine: Part One.

PMID- 8557782
TI  - Influencing the prescribing behaviour of physicians: a metaevaluation.
AB  - Many different interventions have been used to influence the prescribing
      behaviour of physicians, and qualitative evaluations (metaethnography) of such
      interventions have been reported. So far quantitative evaluations of such
      interventions have not been reported; this study is an attempt in that direction.
      Twenty-six published studies (January 1979-September 1991) on the interventions
      for influencing the prescribing behaviour of physicians were pooled and effect
      sizes were extracted. Mean effect size (Zr) was 0.559 and Cohen's d = 0.886.
      Estimated Fail-Safe N was 89. Success rates of interventions varied from 1% to
      99%.

PMID- 8557783
TI  - Continued prescribing of inappropriate drugs in general practice.
AB  - Seven general practitioners used various methods to identify patients in their
      practices whom they had inherited and whose medication they regarded as
      inappropriate in the light of current knowledge. Information was collected in
      each case about the drug concerned, the patient, the original prescriber, and the
      reason for continued prescribing. Each patient was also interviewed. Altogether,
      25 different drugs were prescribed for 40 patients: in 16 the inappropriate drug
      was one acting on the brain, in 13 an antihypertensive, in seven it was given for
      heart disease and in three, for asthma. The influence of the original prescriber,
      and the patient's dependence on the drug, helped to explain its continued use.
      Almost half the patients said that they might consider changing their medication.
      The study underlines the importance of reviewing long-term medication and offers
      a method of scrutinizing repeat prescribing in general practice. Community
      pharmacists could help in this process.

PMID- 8557784
TI  - A survey of drug treatment and outcomes in diabetic patients with acute
      myocardial infarcts.
AB  - Sixty-four diabetic patients suffering an acute myocardial infarct were
      retrospectively matched, by age, gender and smoking habit, to non-diabetic
      controls. The two groups were compared for cardiovascular risk factors, pre
      admission and discharge drug treatment, in-hospital drug treatment, and
      complication and mortality rates. Hypertension was more prevalent in the diabetic
      (63%) than in the control (42%) group. When comparing drugs on admission to those
      at discharge, there was a significant increase in antiplatelet and nitrate usage
      in both groups (P < 0.001), in beta-blocker usage in the control group (P <
      0.001) and in loop diuretic usage in the diabetic group (P < 0.001). The usage of
      angiotensin converting enzyme inhibitors was low: 16% of diabetic patients and 5%
      of controls at discharge. Thrombolytic therapy was used in 29 diabetics and 37
      controls. There was a significantly higher complication rate in the diabetic
      group than in the control group (P < 0.006), the most common being congestive
      cardiac failure (59% vs 30%, P < 0.001). Four controls and 13 diabetic patients
      died; three of the latter had their diabetes diagnosed during the admission. This
      study did not clearly demonstrate any underlying risk factors or treatment
      variables to account for the increased morbidity or mortality in diabetic
      patients with acute myocardial infarct, when compared to a matched non-diabetic
      population. However, modest associations not detected by this relatively small
      study are still possible.

PMID- 8557785
TI  - Relationship between valproic acid dosage, plasma concentration and clearance in
      adult monotherapy patients with epilepsy.
AB  - Significant variability has been reported in the plasma concentration-dose
      relationship for the anticonvulsant compound valproic acid (VPA). Several factors
      may contribute to this observed variability, including heterogeneous patient
      populations of children and adults, polytherapy, and timing of plasma
      concentration sampling. To optimally determine the relationship between trough
      VPA plasma concentration and dose, we evaluated a homogeneous group of adult
      ambulatory patients with epilepsy receiving VPA monotherapy. Furthermore, we
      sought to evaluate whether a relationship existed between VPA dosage and plasma
      clearance for both total and unbound or free drug. Steady-state trough plasma
      concentrations were determined in thirty-two patients. Mean VPA dose was 22.8 +/-
      10.3 mg/kg/day. Mean total and unbound VPA plasma concentrations were 97.9 +/-
      34.9 and 13.2 +/- 10.6 micrograms/ml, respectively. Significant correlations
      between VPA dose and total and unbound plasma concentrations were found (r = 0.82
      and r = 0.85, P < or = 0.001, respectively). Significant relationships were also
      observed between VPA dose and clearance. A positive correlation was noted for
      dose and total plasma clearance (r = 0.61, P < or = 0.001), while an inverse
      correlation existed between dose and unbound VPA plasma clearance (r = -0.51, P <
      0.01). Although a statistically significant correlation does exist between VPA
      dosage and both total and unbound plasma concentrations, significant interpatient
      variability still remains even under 'optimal' therapeutic drug monitoring
      conditions.

PMID- 8557786
TI  - Review of the initiation of anticoagulant therapy.
AB  - The objective was to retrospectively study the initiation of anticoagulant
      therapy in inpatients of the two major teaching hospitals in Tasmania, Australia.
      The medical records of a random sample of patients with an admission diagnosis of
      deep venous thrombosis (DVT) or pulmonary embolism (PE) during the period
      February 1992 to June 1994 were studied, to examine therapeutic issues including
      (i) the time taken after commencing heparin to achieve a therapeutic activated
      partial thromboplastin time (APTT), (ii) when warfarin was commenced, (iii) the
      time taken after commencing warfarin to achieve a therapeutic International
      Normalized Ratio (INR), and (iv) the degree of anticoagulant control at the time
      of discharge from hospital. The medical records of 99 patients (median age: 65
      years and range: 16-93 years; 52 females) were studied. Heparin was generally
      commenced within 4 h of admission to hospital. The median duration of heparin
      therapy was 5 days (range: 2-26 days). The median number of APTTs performed per
      patient was 6 (range: 1-24), with most results (60%) being below the optimum
      range. Warfarin was commenced from day 1 of hospitalization in only 34% of
      patients. The INR was within the therapeutic range in only 29% of cases when
      heparin was ceased. The median time taken to achieve a therapeutic INR after
      starting warfarin was 3 days (range: 1-15 days).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8557787
TI  - Is the number of surgical day cases a good indicator of rising drug costs?
AB  - There have been various attempts to reduce the expenditure on drugs-limited
      lists, drug formularies, prescribing policies, etc. The number of occupied beds
      in hospitals has fallen, and other indicators of hospital work have altered
      little. In spite of this, the expenditure on drugs by the hospitals in Wales has
      continued to rise. Taking two groups (antibiotics and anaesthetic agents) as
      examples of the high-cost drugs, the expenditure has been related to a number of
      indicators of the workload of a hospital. No clear relationship between any one
      indicator has been demonstrated although the number of surgical day cases is an
      important factor.

PMID- 8557788
TI  - Rapid micromethod for simultaneous measurement of oxcarbazepine and its active
      metabolite in plasma by high-performance liquid chromatography.
AB  - A rapid method for the simultaneous determination of oxcarbazepine (OXC) and its
      active metabolite (10-hydroxycarbazepine) in human and rat plasma by reversed
      phase high-performance liquid chromatography is described. The method involves a
      simple one-step extraction of the drugs from plasma with dichloromethane. The
      extract was evaporated and the residue was reconstituted with mobile phase and
      injected onto a Novapak C18 column. The eluting solvent was 20% acetonitrile in
      water at a flow rate of 1.5 ml/min and the detector was monitored at 215 nm. The
      detection limit of OXC and 10-hydroxycarbazepine was 50 and 20 ng/ml,
      respectively. The within-day and between-day coefficients of variation for OXC
      and its active metabolite were 2.57-6.95% and 4.21-8.3%, respectively. The
      relative and absolute recoveries varied between 71.4% and 104.0%. The
      applicability of the analytical procedure to pharmacokinetic studies was
      illustrated.

PMID- 8557789
TI  - Dental properties of antiseptic throat lozenges formulated with sugars or
      Lycasin.
AB  - Thirteen different formulations of throat lozenges were examined for their
      acidity, demineralizing action on hydroxylapatite, and fermentability by human
      dental plaque micro-organisms. Their flavouring acids gave them low pH values in
      the range 2.6-3.7, leading to the dissolution of calcium and phosphorus from
      hydroxylapatite. The combination of antiseptics and flavouring acids in the
      lozenges inhibited microbial growth and metabolism. In the absence of any
      antiseptics and flavouring acids, the growth and metabolic activity of cultures
      of plaque micro-organisms were significantly greater on sucrose+glucose lozenges
      than on a new Lycasin formulation.

PMID- 8557790
TI  - In vitro dissolution studies on nifedipine capsules.
AB  - The in vitro dissolution rates of 5 and 10 mg nifedipine capsules from eight
      suppliers were measured in simulated gastric fluid using the rotating paddle
      apparatus. A total of fourteen products were tested and the performance was found
      to be satisfactory for all products (> 80% dissolution in 20 min).

PMID- 8557791
TI  - Helicobacter pylori and peptic ulcer disease: current status.

PMID- 8557792
TI  - A pause in cardiac rhythm detected before neck surgery.

PMID- 8557793
TI  - Scientific literacy.

PMID- 8557794
TI  - Retraining specialists for primary care.

PMID- 8557795
TI  - When 'low tech' is better.

PMID- 8557796
TI  - Palpitations and lightheadedness in a 42-year-old man.

PMID- 8557797
TI  - A case of calcium channel blocker overdose.

PMID- 8557798
TI  - Case in point. Tophaceous gout.

PMID- 8557799
TI  - Caring for the terminally ill.

PMID- 8557800
TI  - CT-guided needle biopsy.

PMID- 8557801
TI  - Steps toward gene therapy: 1. The initial trials.
AB  - Hopes for correcting the instruction tape in patients with genetic disease are
      being intensively explored. Initial efforts centered on monogenic
      immunodeficiency states, but in a pattern not wholly expected by researchers, the
      "acquired genetic diseases" of cancer and AIDS account for most ongoing clinical
      trials. Experience with adenosine deaminase deficiency shows the difficulties
      encountered in creating practical gene therapies.

PMID- 8557802
TI  - Pharmacologic management of cancer pain.
AB  - Pain control should be a priority in cancer care. For most patients, the basic
      strategies are straightforward and pharmacologic: Up to 85% of cancer pain can be
      managed with oral agents. Barriers arise from misconceptions about opioids. The
      greatest single problem may be inadequate pain assessment--a deficiency that can
      be rectified by relying on patients to rate their pain.

PMID- 8557803
TI  - Helping patients live with asthma.
AB  - Few patients with asthma receive sufficient basic training in routine self-care.
      Even young children can learn to keep track of their symptoms, use a peak flow
      meter, and recognize when bronchodilator and anti-inflammatory drug dosages must
      be stepped up. Moreover, more than half of patients have chronic inflammatory
      airway disease, yet most of them are not being treated for the inflammatory
      component of their disorder.

PMID- 8557804
TI  - Viral arthritis: the lessons of parvovirus B19.
AB  - Viruses are among the most common and least recognized causes of joint symptoms-
      including syndromes misclassified as seronegative rheumatoid arthritis.
      Parvovirus B19 is notably underappreciated in this role. Many cases resolve
      spontaneously. The challenge is to exclude nonviral causes of joint disease.

PMID- 8557805
TI  - Zollinger-Ellison syndrome: diagnosis and management.
AB  - Patients with peptic ulcer disease who do not have Helicobacter pylori infection
      or a history of NSAID use may have the syndrome. Acid secretion can be controlled
      medically, and tumor resection may be curative in selected patients.

PMID- 8557806
TI  - Estimating premorbid intelligence in African-American and white elderly veterans
      using the American version of the National Adult Reading Test.
AB  - Knowledge of earlier intellectual functioning can be very helpful in the
      diagnosis of neurocognitive disorders. The National Adult Reading Test (Nelson,
      1982), based on the observation that reading irregularly spelled words remains
      intact in mild dementia, may be useful for this purpose. A version for speakers
      of American English (AMNART) was recently published (Grober & Sliwinski, 1991).
      The present study evaluated the validity of the AMNART with demented and
      nondemented African-American and White elderly veterans. The average differences
      between African-American and White participants on the AMNART and WAIS-R were
      similar. The differences between demented and nondemented patients were greater
      on the WAIS-R than on the AMNART, as expected. Paradoxically, the AMNART appears
      to over-estimate IQ among nondemented individuals with lower WAIS-R scores, but
      underestimate IQ among more impaired demented patients. Using Grober and
      Sliwinski's (1991) 10-point discrepancy rule between AMNART and WAIS-R VIQ
      scores, 70% of demented and nondemented veterans were successfully classified. No
      discontinuation rule for the AMNART could be established because word difficulty
      order varies across samples.

PMID- 8557808
TI  - Dense amnesia in a professional musician following herpes simplex virus
      encephalitis.
AB  - We describe the memory functioning of C, a professional musician who became
      amnesic following herpes simplex encephalitis in 1985. Although transient amnesia
      in a professional musician has previously been described, this is the first
      reported case of chronic amnesia in a highly talented professional musician. C is
      unusual in three respects. First, his amnesia is particularly severe. Second, his
      amnesia includes semantic as well as episodic memory deficits. Third, he believes
      he has just woken up and his preoccupation with this state of 'just wakening' has
      persisted for over 9 years. This appears to be the result of a delusion rather
      than the consequence of his amnesia.

PMID- 8557807
TI  - Visual attention and perception in patients with Huntington's disease:
      comparisons with other subcortical and cortical dementias.
AB  - Shifts in attention were examined in patients with Huntington's disease (HD)
      using a divided attention paradigm that involved the presentation of global-local
      stimuli. The HD patients' pattern of performance was compared to the previously
      reported results of groups of patients with Alzheimer's disease (AD; Filoteo et
      al., 1992) or Parkinson's disease (PD; Filoteo et al., 1994). Across consecutive
      trials of the divided attention task, a visual target could appear at either the
      same global-local level or at a different level. When the target changed levels
      across consecutive trials, the AD patients demonstrated an impairment in
      disengaging attention from the level at which the last target appeared, whereas
      the PD patients were impaired in maintaining their attention at the previously
      attended level. In contrast to these patterns of performances, the HD patients
      did not demonstrate a significant impairment in shifting attention between
      hierarchical levels. Both the AD and the PD patients' abnormal shifting ability
      was significantly related to the number of errors they made in identifying target
      stimuli; however, the pattern of the relationship was qualitatively distinct.
      These results suggest that different attentional mechanisms may underlie AD and
      PD patients' visual-perceptual deficits. The HD patients' shifting ability was
      not related to the number of errors they made in identifying target stimuli,
      suggesting that a different mechanism may account for the visual-perceptual
      impairments exhibited by these patients.

PMID- 8557809
TI  - Objective criteria for reporting language dominance by intracarotid amobarbital
      procedure.
AB  - We propose a standardized method for reporting language lateralization by
      intracarotid amobarbital procedure (IAP). We retrospectively reviewed 165 IAPs,
      and classified language lateralization as left, right, or bilateral by three
      different methods, all based on the duration of speech arrest following each
      injection: absolute duration, side-to-side difference, and a "laterality index"
      defined as (L-R/L+R). Cutoff values were obtained by studying a pure subgroup of
      left hemisphere dominant right-handed subjects. In 142 patients (86%), the
      classification remained unchanged among all three methods: left in 112 (79%),
      right in 19 (13%), and bilateral in 11 (8%). In the other 23 patients (14%),
      language classification varied among the three criteria used. The change of
      category was never between left and right, and always involved bilateral
      language. Thus, this index may be helpful in standardizing and comparing IAP
      results from different series.

PMID- 8557810
TI  - Components in the visual processing of known and unknown faces.
AB  - This study investigated the neural basis and cognitive mechanisms of disorders
      affecting the visual processing of human faces. Two patients affected by
      prosopagnosia (PA), 45 unilateral brain-damaged patients not previously selected
      for gnosic disturbance, and 52 normal subjects were administered three tasks
      involving visual matching of unfamiliar faces, identification of famous faces,
      and age attribution to unknown faces. Results confirmed that the right hemisphere
      (and particularly the posterior region) is critical for all of the main aspects
      of facial processing. Neuroradiological and PET examination in both PA patients
      revealed a lesion in the territory of the right posterior cerebral artery (infero
      mesial areas of temporal and occipital lobes). Moreover, group comparisons showed
      that patients affected by a right posterior lesion obtained the worst scores on
      all tasks of our battery. Both group comparisons and single-case analyses pointed
      out that a deficient recognition of familiar faces is generally independent of
      perceptual disorders and, as such, should be considered mnestic in nature.
      Disorders in the age attribution, on the contrary, appear to be strictly
      associated with deficits in the perceptual analysis of unfamiliar faces.

PMID- 8557811
TI  - Comparison of the California Verbal Learning Test and the Rey Auditory Verbal
      Learning Test in head-injured patients.
AB  - Performances of moderate and severe closed-head-injury patients were compared on
      the California Verbal Learning Test (CVLT) and Rey Auditory Verbal Learning Test
      (RAVLT). Results showed that raw scores were highly correlated between tests.
      There were no significant between-test differences in mean raw scores. However,
      standard scores calculated from existing CVLT and RAVLT norms were significantly
      lower on the CVLT than on the RAVLT. Furthermore, there were differences between
      the various RAVLT norm sets. The results indicate that although the CVLT and
      RAVLT measure similar cognitive processes in closed-head-injury patients, there
      are major discrepancies in test interpretation using existing norms. Test and
      norm set selection significantly influence the likelihood of a patient being
      classified as memory-impaired.

PMID- 8557812
TI  - Grouped data do not tell the whole story: individual analysis of cognitive change
      after temporal lobectomy.
AB  - Studies of group measures of central tendency describe the cognitive sequelae of
      anterior temporal lobectomy; however, information regarding clinically
      significant change is scarce. This study examined the frequency of clinically
      significant variability (i.e., a change score > or = 1 standard deviation from
      preoperative to postoperative performance) in 50 temporal lobectomy patients (19
      left-sided; 31 right-sided). A range of cognitive domains was examined. Most
      (68%) indices showed no change. Of those that changed, an approximately
      equivalent number were losses and gains. Such results do not support restricting
      surgical treatment of epilepsy to avoid major cognitive decline. In right
      handers, the observance of material-specific memory decline was variable. Only
      36% of right-handers with left-temporal lobectomy showed only postsurgical loss
      in verbal memory, while 50% showed both losses and gains across several verbal
      memory measures. Almost 60% of right-temporal lobectomy patients exhibited some
      verbal memory loss, but only one-third showed nonverbal memory loss. We conclude
      that group studies identifying material-specific memory loss overestimate the
      consistency and pervasiveness of the negative effects of temporal lobectomy.

PMID- 8557813
TI  - Handedness and other laterality indices in women prenatally exposed to DES.
AB  - A group of 175 women who had been exposed to diethylstilbestrol (DES) prenatally
      were compared with 219 unexposed control subjects on four laterality indices:
      handedness, footedness, eyedness, and earedness. It was found that there was a
      higher incidence of left-handedness among the DES-exposed subjects than among the
      controls. It was concluded that intrauterine exposure to the synthetic estrogen
      DES disturbs the normal process of cerebral lateralization. The mechanism by
      which this takes place is still unknown.

PMID- 8557814
TI  - Assessment of visual memory: a comparison of Chinese characters and geometric
      figures as stimulus materials.
AB  - The study compared the suitability of geometric figures and Chinese characters
      for assessing visual memory. In Study 1, 40 Chinese characters were found to be
      significantly less verbalisable than were 40 geometric figures from the Biber
      Figure Learning Test. In Study 2, memory for Chinese characters, for Biber
      figures, and for items on the Rey Auditory Verbal Learning Test were compared
      using 14 subjects with left cerebrovascular accident, 15 subjects with right
      cerebrovascular accident, and 29 matched controls. Subjects in the left
      hemisphere group showed impairment on the Rey Auditory Verbal Learning Test but
      not on Chinese characters, whereas subjects in the right hemisphere group showed
      impairment on Chinese characters but not on the Rey Auditory Verbal Learning
      Test. This double dissociation was not evident when comparisons involved the
      Biber Figure Learning Test. The Chinese character set used in this study was thus
      judged to be more suitable than were geometric figures in the Biber Figure
      Learning Test for assessing visual memory.

PMID- 8557815
TI  - Concept generation: validation of a test of executive functioning in a normal
      aging population.
AB  - A new test, Concept Generation, was designed to fractionate the processes that
      underlie sorting performance in an efficient paper-and-pencil format. The test
      was administered to 60 subjects, aged 18-79. Results indicated age-related
      deficits for self-initiated concept formation, shifting set, output monitoring,
      and perseverative tendencies. When cuing was introduced to increase structure,
      age group differences were attenuated or eliminated. Within the older group,
      subgroups were identified based upon the nature of their repetitions. The
      hypothesis that sorting behavior is mediated by executive functions led to
      correlational analyses between Concept Generation scores and other measures of
      executive functioning. The pattern of correlations supported the construct
      validity of the Concept Generation test. In addition to providing preliminary
      evidence for the usefulness of Concept Generation in executive functioning
      assessment, the results replicated and extended previous work on executive
      functioning in older individuals.

PMID- 8557816
TI  - Meta-analytic comparison of the components of visual cognition in Parkinson's
      disease.
AB  - Controversy surrounds the presence of deficits of visual cognition in Parkinson's
      Disease. This literature has been seriously undermined by a number of
      methodological and theoretical faults that make interpretation of this hypothesis
      difficult. This review proposes a structure of visual cognition composed of 13
      aspects. A meta-analysis of these components on 70 studies that used standardised
      neuropsychological tests and an appropriate normal control group indicates that
      the PD subjects are significantly compromised on tests of attention and
      concentration, complex visuospatial functions, and multifactorial spatial
      functions. More detailed analysis of the basic components of visual cognition was
      not undertaken due to low statistical power; hence, it remains unclear whether
      these subjects have primary visual processing deficits in association with their
      higher order deficits. The observed deficits may be interpreted as being a
      consequence of either undetermined lower level visual cognitive deficits or a
      compromise in executive functioning.

PMID- 8557817
TI  - Neuropsychological test performance of specific diagnostic groups in the Canadian
      Study of Health and Aging (CSHA).
AB  - An overview of specific neuropsychological data from the Canadian Study of Health
      and Aging is presented. Variables of interest were diagnosis (no cognitive
      impairment, cognitive loss without dementia, and dementia), language of test
      administration (French or English), and residence (community or institution).
      Persons with dementia scored below persons without dementia on all
      neuropsychological measures except the naming of coloured tokens. Some test
      differences were small and not clinically meaningful while others were
      substantial. In particular, and as expected, memory function differed between the
      groups. Language of test administration and place of residence also influenced
      neuropsychological results independently of diagnosis. Scores differed on some
      tests (primarily, visuospatial) depending on whether participants lived in
      institutions or in the community. Persons tested in French scored below those
      tested in English on many language-based tests.

PMID- 8557818
TI  - Working memory as assessed by subject-ordered tasks in patients with obsessive
      compulsive disorder.
AB  - We tested patients with obsessive-compulsive disorder (OCD) and normal subjects
      (n = 18 per group) on a self-paced, working memory task that, based on studies of
      patients with focal brain lesions and functional brain imaging studies of
      normals, is largely mediated by prefrontal cortex. The OCD patients had normal
      working memory spans and normal recognition memory for all types of material
      tested (abstract words, common objects, and novel nonsense objects). The
      patients, however, were slow (p < .005), and the time they took to complete the
      tasks was significantly correlated with ratings of OCD symptoms (r = .539, p <
      .05) and depression (r = .643, p < .01), but not anxiety. Slowed performance on
      this self-paced task was discussed in relation to normal response times by OCD
      patients under typical laboratory conditions. It was suggested that this
      discrepancy may be related to a broader dissociation between real-world and
      laboratory performance as seen in some patients with prefrontal lobe dysfunction.

PMID- 8557819
TI  - Odor identification as an early marker for Alzheimer's disease: impact of lexical
      functioning and detection sensitivity.
AB  - The impact of lexical functioning and detection sensitivity on the deficit of
      odor identification in Alzheimer's disease (AD) was studied in persons diagnosed
      with probable and questionable AD. Tests consisted of lexical-based odor
      identification, lexical-based picture identification, picture-based odor
      identification, and odor-detection threshold. Results suggest (1) that odor
      identification is poorer than picture identification in probable and questionable
      AD, (2) that odor identification continues to be poor even when lexical demands
      are eliminated, (3) that odor detection does contribute to the odor
      identification deficit, but does not account for it completely, and (4) that odor
      identification tests have a correct classification rate of 83-100%. Odor
      identification tests can be very useful tools in diagnosing AD and should be
      considered an important addition to existing diagnostic test batteries.

PMID- 8557820
TI  - Corticotropin-releasing hormone is involved in conditioned stimulus-induced
      reduction of natural killer cell activity but not in conditioned alterations in
      cytokine production or proliferation responses.
AB  - Research from our laboratory has demonstrated that the presentation of an
      aversive conditioned stimulus produces pronounced suppression of several in vitro
      measures of immune status. The present study was designed to evaluate the role of
      central corticotropin-releasing hormone (CRH) in the mechanisms mediating these
      conditioned effects. The aversive conditioned stimulus was a distinct environment
      that had previously been associated with electric footshock. Lewis rats received
      intraventricular administration of either buffered saline or a dose of the CRH
      selective receptor antagonist alpha-helical CRH(9-41) (0, 0.5, 5, or 50
      micrograms) prior to exposure to the aversive conditioned stimulus or home cage
      control treatment. The aversive conditioned stimulus produced decreases in
      splenic natural killer cell activity, splenocyte responsiveness to the mitogens
      concanavalin A (ConA), phytohemagglutinin (PHA), lipopolysaccharide (LPS), and
      the combination of ionomycin and phorbol myristate acetate (PMA), blood leukocyte
      responsiveness to ConA and PHA, and the production of interleukin-2 and
      interferon-gamma by activated splenocytes. The conditioned stimulus also produced
      an increase in plasma levels of corticosterone. Pretreatment with alpha-helical
      CRH(9-14) completely blocked the conditioned stimulus-induced suppression of
      natural killer cell activity. The CRH antagonist had no attenuative effect on the
      conditioned suppression of splenocyte or blood leukocyte proliferation in
      response to mitogens, or the production of interleukin-2 or interferon-gamma by
      activated splenocytes. There was also no effect of alpha-helical CRH(9-14) on the
      conditioned stimulus-induced increase in plasma corticosterone. These findings
      suggest that conditioned stimulus-induced suppression of natural killer cell
      activity is mediated by a mechanism that involves activity at central CRH
      receptors, and that this conditioned modulation is independent of HPA activation.
      Furthermore, these results indicate that the mechanisms involved in conditioned
      stimulus-induced suppression of proliferative or cytokine production responses
      are distinct from those involved in the modulation of natural killer cell
      activity.

PMID- 8557821
TI  - The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces
      acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat.
AB  - Using a highly purified recombinant protein, mMOG, we demonstrated that
      autoimmune responses to the N-terminal domain (a.a 1-125) of the myelin
      oligodendrocyte glycoprotein (MOG) induce an acute demyelinating variant of
      experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Immunisation
      with 100 micrograms of mMOG in adjuvant at the base of the tail induced mild
      clinical disease in 9 of 11 animals (mean clinical score 1.1). The disease was
      characterised histopathologically by the presence of inflammation and focal
      demyelinating lesions in the central nervous system (CNS). Adoptive transfer
      experiments suggest that this inflammatory demyelinating pathology is mediated by
      synergy between a weakly encephalitogenic, MOG-specific T cell response and a
      demyelinating, MOG-specific autoantibody response. Using in vitro selected mMOG
      reactive T cell lines, the encephalitogenic T cell response to this domain of MOG
      was found to recognise two distinct epitopes, MOG1-20 and MOG35-55; whereas ELISA
      demonstrated that the immunodominant B cell epitope was located within the amino
      acid sequence MOG1-25. However although active immunisation with synthetic
      peptides corresponding to the T cell epitopes, MOG1-20 or MOG35-55, induced an
      inflammatory response in the CNS, this was not associated with demyelination
      indicating that the demyelinating antibody response recognises other, possibly
      conformation dependent epitopes. This study unequivocally demonstrates that MOG
      specific autoimmune responses are alone sufficient to induce a demyelinating
      disease of the CNS and supports the proposal that MOG may play an important role
      in the immunopathogenesis of multiple sclerosis.

PMID- 8557822
TI  - Systemic passive transfer studies using IgM monoclonal antibodies to sulfatide.
AB  - We present a patient with benign IgM-gamma anti-Sulfatide (SUL) whose neuropathy
      was transferred in newborn rabbits. The patient's clinico-pathological picture of
      anti-SUL-associated demyelinating neuropathy is reported. The monoclonal IgM
      antibodies prepared by Tatum's method, that retained their biological activity,
      were passively transferred to newborn rabbits. The passive transfer produced
      demyelinating nerve lesions very similar to the donor antibody neuropathy. In
      experimental lesions we observed the human IgM anti-SUL antibodies binding to
      Schmidt-Lanterman incisures and nodes of Ranvier. We postulate that the myelin
      specific and complement-dependent lesions observed in the peripheral nerve
      support the potential demyelinating role of anti-SUL antibodies. Moreover, the
      pattern of the antibody binding to the perineuronal sheath of satellite cells in
      dorsal root ganglia strengthen the hypothesis that anti-SUL antibodies may have a
      pathogenetic role in this sensorimotor syndrome.

PMID- 8557823
TI  - Lymphocyte phenotype and subset distribution in normal cerebrospinal fluid.
AB  - The distribution of lymphocyte subpopulations in cerebrospinal fluid (CSF) and
      their phenotypic characteristics were extensively investigated in a group of 18
      healthy individuals using two- and three-color flow cytometry. Generally, CD3+ T
      lymphocytes constituted the vast majority of CSF lymphocytes while the number of
      B lymphocytes and NK cells were low. Most T lymphocytes exhibited the phenotype
      of memory/primed cells in both the CD4+ and CD8+ subpopulations. Two markers for
      recent activation, HLA-DR and interleukin-2 receptor (CD25) were not upregulated
      when compared with peripheral blood (PB) in the majority of CSF T lymphocytes.
      However, a fraction of T lymphocytes co-expressing the NK cells markers CD56
      and/or CD16 showed a pronounced upregulation of HLA-DR in CSF as compared with
      PB. This study documents that the cellular composition of the normal CSF differs
      profoundly from PB regarding all major lymphocyte subpopulations. This has to be
      taken into account in studies addressing questions regarding cellular immune
      reactions in the central nervous system under pathological conditions.

PMID- 8557824
TI  - Limited T cell receptor usage by HTLV-I tax-specific, HLA class I restricted
      cytotoxic T lymphocytes from patients with HTLV-I associated neurological
      disease.
AB  - T cell receptor (TCR) V alpha and V beta chain usage of HTLV-I tax-specific, HLA
      class I restricted CD8+ cytotoxic T cells (CTL) was determined from lymphocytes
      obtained from peripheral blood of patients with HTLV-I associated neurological
      disease. To characterize TCR repertoire, CD8+ lymphocytes from peripheral blood
      were cloned in limiting dilution, and the resulting wells were screened for HTLV
      I-specific precursor CTL activity. RNA was isolated from HLA-A2 restricted HTLV-I
      tax peptide-specific (tax 11-19; LLFGYPVYV) CD8+ CTL lines and cDNA was analyzed
      by PCR amplification using V alpha and V beta chain family-specific
      oligonucleotide primers. The results indicate that CD8+ cytotoxic T cell lines
      from HLA-A2 HAM/TSP patients express a limited repertoire of T cell receptor
      chains which may correlate with duration and severity of disease. The restricted
      use of TCR genes expressed by antigen-specific CTL may play a critical role in
      the pathogenesis of HAM/TSP and may be of value in developing immunotherapeutic
      strategies that focus on eliminating these cells or inhibiting their activity.

PMID- 8557825
TI  - Colony-stimulating factors regulate programmed cell death of rat microglia/brain
      macrophages in vitro.
AB  - Programmed cell death of activated microglia appears to be one mechanism how
      steady state of microglia is achieved in vivo. Programmed cell death of microglia
      might result either from the downregulation of microglial mitogens/survival
      factors or from signals which directly induce microglial cell death. To further
      elucidate the mechanisms regulating programmed cell death in microglia, growth
      factor and cytokine dependence of microglial proliferation and cell death have
      been examined in vitro in microglia/brain macrophage cultures established from
      neonatal rat brain. Microglial proliferation was assessed by PCNA labelling and
      DNA fragmentation by the TUNEL technique in the presence or absence of several
      cytokines including IL-1, IL-6, TGF beta 1, TNF alpha, M-CSF and GM-CSF. Results
      of TUNEL labellings were supplemented by gel electrophoretic analysis of DNA
      extracted from cultured microglia which showed laddering of DNA fragments. Of all
      cytokines/growth factors tested, GM-CSF and M-CSF were not only the strongest
      microglial mitogens but, moreover, withdrawal of M-CSF or GM-CSF significantly
      enhanced rates of microglial cell death by DNA fragmentation. Expression of
      microglial growth factors, in particular colony-stimulating factors, may thus be
      instrumental in controlling steady states of microglia in the injured nervous
      system.

PMID- 8557826
TI  - Anti ICAM-1 (CD 54) monoclonal antibody reduces inflammatory changes in
      experimental bacterial meningitis.
AB  - We investigated whether monoclonal antibodies directed against intracellular
      adhesion molecule 1 (ICAM-1 mAb) inhibit brain edema, increase of intracranial
      pressure (ICP), regional cerebral blood flow (rCBF) and recruitment of white
      blood cells (WBC) into the cerebrospinal fluid (CSF) in the rat model of the
      early phase of bacterial meningitis. Brain edema was assessed by brain water
      content determinations. rCBF measured by laser Doppler flowmetry and ICP were
      recorded continuously for 6 h after intracisternal challenge. Meningitis was
      induced with pneumococcal cell walls (PCW). Increase of ICP and brain water
      content were significantly inhibited (P <0.05) by intravenous treatment with ICAM
      1 mAb (TM-8, 1 mg/kg). Furthermore, ICAM-1 mAb treatment profoundly attenuated (P
      <0.05) rCBF increase and WBC invasion into the CSF. These results suggest that
      the ICAM-1 pathway is critically involved in the early phase of bacterial
      meningitis.

PMID- 8557827
TI  - The development of sexual dimorphism in natural killer cell activity and
      resistance to tumor metastasis in the Fischer 344 rat.
AB  - The development of sexual dimorphism in the number and activity level of natural
      killer (NK) cells was studied in the inbred Fischer 344 rat from prepubescence to
      maturity. Additionally, in view of the biological significance of NK cells in
      controlling cancer, especially the metastatic process, we used a syngeneic
      mammary tumor (MADB106) to assess the host anti-metastatic activity. This tumor
      model was used because NK cells control the lung clearance of i.v.-injected
      MADB106 tumor cells, a process that critically affects the metastatic
      colonization of these tumor cells in the lungs. The results indicated that
      although prepubescent (36 days of age) males and females exhibited greater NK
      cytotoxicity (assessed in vitro) and higher anti-metastatic activity, evidenced
      by fewer tumor cells retained in the lungs. On the other hand, the mature males
      (140-170 days of age) displayed greater LGL/NK number and activity per ml blood,
      retained fewer tumor cells, and developed fewer lung tumor colonies compared to
      the females. During early postpubescence (63 days of age), a transitional stage
      between prepubescence and maturity, females and males exhibited equivalent
      numbers of circulating LGL/NK cells, and females displayed slightly greater NK
      cytotoxicity per ml blood yet retained somewhat greater numbers of tumor cells
      compared to the males. Overall, whereas the males exhibited increasing levels of
      NK number and activity throughout the age span tested, the females, despite
      displaying greater NK function compared to the males at prepubescence and slight
      improvement at postpubescence, fell behind the males in these indices of NK
      function at maturity.

PMID- 8557828
TI  - Suppression of experimental autoimmune myasthenia gravis and experimental
      allergic encephalomyelitis by oral administration of acetylcholine receptor and
      myelin basic protein: double tolerance.
AB  - Oral administration of acetylcholine receptor (AChR) or myelin basic protein
      (MBP) to Lewis rat prior to immunization with AChr or MBP and complete Freund's
      adjuvant (CFA) has previously been shown to prevent or delay the onset of
      experimental autoimmune myasthenia gravis (EAMG) or experimental allergic
      encephalomyelitis (EAE), which represent animal models of myasthenia gravis and
      multiple sclerosis, respectively. Here we show that Lewis rats immunized with
      AChr+MBP+CFA developed both signs of muscular weakness seen in EAMG and paresis
      characteristic for EAE. This disease was associated with high levels of anti-AChR
      and anti-MBP antibody secreting cells and of AChR- and MBP-reactive INF-gamma
      secreting Th1-like cells in lymph nodes. The diseased rats also showed
      upregulation of AChR- and MBP-induced mRNA expression of IFN-gamma in lymph node
      cells. Oral tolerization with AChR and MBP in combination prior to immunization
      with AChR+MBP+CFA alleviated clinical disease as well as AChR- and MBP-specific B
      cell node cells. The results implicate that oral tolerization simultaneously to
      more than one autoimmune disease-related autoantigen is feasible, and that
      suppression of autoantigen-induced IFN-gamma and augmentation of TGF-beta are
      pivotal in tolerance induction.

PMID- 8557829
TI  - Analysis of cytokine expression in muscle in inflammatory myopathies, Duchenne
      dystrophy, and non-weak controls.
AB  - We investigated the profiles of cytokine mRNA expression in muscle in 15 cases of
      inflammatory myopathy (IM) (5 each of polymyositis, inclusion body myositis, and
      dermatomyositis) and in 10 controls (5 of Duchenne dystrophy and 5 non-weak
      subjects). Expressions of the predominantly T cell-derived cytokines (interleukin
      (IL)-2, IL-4, IL-5, and interferon-gamma (IFN-gamma), of the predominantly
      macrophage-derived cytokines (IL-1, IL-6, and tumor necrosis factor-alpha (TNF
      alpha)), as well as cytokines that can be of either T cell or macrophage origin
      (granulocyte-macrophage colony stimulating factor (GM-CSF) and transforming
      growth factor beta 1 (TGF-beta 1) and TGF-beta 2), were monitored by the reverse
      transcriptase-PCR method. The expression of T cell cytokine mRNAs for IL-2, IL-5,
      and IFN-gamma was generally weak or inconsistent. IL-4 mRNA expression was
      consistently moderate to strong in polymyositis but generally weak or absent in
      the other IMs. The expression of macrophage cytokine mRNAs for IL-1 alpha and IL
      1 beta was weak or absent in all cases. Variable TNF-alpha mRNA expression was
      observed in 12 of 15 IM cases and faint or weak expression in 5 of 10 controls.
      Very strong GM-CSF expression was detected, but only on boosted PCR, in 12 of 15
      cases of IM but in none of the controls. IL-6 was expressed only weakly or
      inconsistently. In contrast to the variable expression of several of the above
      mentioned cytokine mRNAs, all IM specimens strongly expressed TGF-beta 1 mRNA and
      12 of 15 strongly expressed TGF-beta 2 mRNA. Thus, with the exception of IL-4
      expression in polymyositis, a similar pattern of cytokine mRNA expression exists
      in the different types of IMs. Moreover, this pattern resembles that detected in
      non-weak and DD controls, although expression is generally weaker in the non-weak
      controls. The findings suggest that in IM muscle a sustained secretion of
      cytokines by T cells or of IL-1 by macrophages is not a prerequisite for
      operation of the immune effector response and that muscle may not be the site of
      ongoing sensitization.

PMID- 8557830
TI  - Relations between infant neurobehavioral performance and cognitive outcome in
      very low birth weight preterm infants.
AB  - The predictive utility of three aspects of neonatal neurobehavioral performance
      was examined in 144 very low birth weight (< 1500 g) preterms who were followed
      until 6 years of age. Visual-following and auditory-orienting composites derived
      from the Einstein Neonatal Neurobehavioral Assessment Scale were modestly related
      to the Mental Developmental Index (MDI) and IQ scores at several ages, whereas
      the active motility composite was only related to MDI scores at 1 year of age
      (corrected). Infants who showed deviant performance on both visual following and
      auditory orienting composites had significantly lower cognitive test scores at 1
      and 6 years of age and were more likely to be classified as subaverage at 6 years
      of age (IQ < 85). Group differences were independent of both neonatal health
      status and motor scores and were not due to the performance of children with
      severe sensory impairments. These findings suggest that visual following and
      auditory orienting measured in the neonatal period can offer a useful way of
      indexing initial capacities.

PMID- 8557831
TI  - Early childhood surveillance of developmental disorders by a birth defects
      surveillance system: methods, prevalence comparisons, and mortality patterns.
AB  - The prevalence of developmental disabilities in early childhood is not well
      documented. An established birth defects registry extended surveillance to
      identify cases of developmental disorders in early childhood by adding all known
      sources of diagnosis and service to case-finding methods. Residents of a
      northwest Arkansas region born during 1985 to 1987 and diagnosed with either a
      birth defect or a developmental disorder by the 4th birthday comprised the
      studied cohort. Case records were linked with death certificates to examine the
      influence of mortality on prevalence ratios. Prevalence ratios estimated were
      64.5/1000 resident live births (60.9/1000 among survivors to age 4 years) for
      either birth defect or developmental disorder, 33.4/1000 for developmental
      disorder, 37.0/1000 for birth defect, and 9.5/1000 for both developmental
      disorder and birth defect. Prevalence ratios of specific developmental disorders
      and the role of mortality in decreasing population prevalence are reported. The
      most common diagnostic categories in this age group were developmental delay,
      seizures, and failure to thrive. Overlap of birth defect categories with a
      diagnosed developmental disability was examined; 68.8% of children diagnosed with
      neural tube defects and 45.5% of those with chromosomal abnormalities who
      survived to age 4 years had clinically diagnosed developmental disorders. An
      anticipated high degree of overlap (77%) for other central nervous system defects
      was found. For other birth defect categories, developmental disorder diagnosis
      was present in 20 to 30% of the study group. Death before age 4 years occurred
      most often when the diagnosis was newborn seizures (17.1%) or "conditions of the
      brain" (13.6%); the mortality rate was 6 to 8% for epilepsy or seizure disorders,
      mental retardation, and vision loss. The large number of developmental diagnoses
      among this cohort indicates that surveillance of these disorders in early
      childhood, even with tentative diagnoses, is feasible. Data obtained indicate
      that many birth defects are associated with developmental disorders; potentially,
      this association can contribute to earlier identification of developmental
      disorders in childhood.

PMID- 8557832
TI  - School-age follow-up of a single-dose prophylactic surfactant cohort.
AB  - This study reports the school-age developmental and health status of a
      preventilatory surfactant cohort. The sample consisted of 39 surviving subjects
      (21 experimental and 18 controls) born at 25 to 29 weeks gestation who were
      studied at 6 and 12 months and 5 to 7 years of age. At 6- and 12-month follow
      ups, the cohort was functioning close to the population normative mean. Although
      cognitive and motor assessments at school age also showed no group differences, 8
      of 19 (42%) in the surfactant group and 9 of 17 (53%) in the normal saline group
      attained a McCarthy General Cognitive Index score of < or = 84 (abnormal range).
      On the Connors' Parental Questionnaire, both groups scored high on the Learning
      Disability Subscale. The surviving cohort at 5 to 7 years had no identified long
      term sequelae due to surfactant therapy, yet both groups were at risk for
      neurodevelopmental and educational morbidity.

PMID- 8557833
TI  - Psychosocial correlates of chronic fatigue syndrome in adolescent girls.
AB  - Behavior problems and family functioning were investigated in a sample of 10
      adolescent girls with chronic fatigue syndrome (CFS), 10 matched healthy
      adolescent girls, and 10 adolescents with childhood cancer in remission. Based on
      the adolescent girls' reports, the CFS group had significantly higher scores than
      the cancer and healthy comparison adolescent girls on somatic complaints and also
      significantly higher scores than the cancer controls on internalizing symptoms
      and depression. Parent reports resulted in significantly higher scores in the CFS
      group than the adolescent girls from the healthy comparison groups on
      internalizing scores and somatic complaints. There were no significant
      differences on any family variables.

PMID- 8557834
TI  - Problem behaviors in inner-city adolescents with chronic illness.
AB  - This study examines the prevalence of problem behaviors (sexual activity,
      substance use, delinquency, and school failure) in a clinical hospital-based
      sample of 217 inner-city, 14 to 17 year olds with a variety of serious, chronic
      medical illnesses and compares this prevalence to that in a group of 121 similar
      aged, healthy friends with no known chronic illnesses living in the same
      community. No differences were found between groups in substance use,
      delinquency, percent who had ever had sexual intercourse, or mean age at first
      intercourse. There was a significant interaction effect of chronic illness and
      gender on age at first intercourse (p = .015); boys without chronic illness
      initiated sexual intercourse at a younger age than their girlfriends without
      illness. Contrary to expectations, significantly more of the healthy friends had
      repeated a grade in school than had those with chronic illness (p = .002).
      Results are discussed in terms of the interrelationships of chronic illness,
      gender, and environment on problem behaviors.

PMID- 8557835
TI  - Are maternal health behaviors related to preschool children's adjustment? A
      preliminary report.
AB  - Little is known about how parental health behaviors affect others within the
      family. This study examined the relationship of mothers' health behaviors to
      mothers' reports of their preschool children's mental health. Mothers (n = 89) of
      2 and 3 year olds completed a mail survey assessing a variety of health related
      measures. Children's adjustment was assessed by the Child Behavior Checklist, a
      well established measure of child adjustment. The Personal Lifestyle
      Questionnaire and Perceived Stress Scale were also contained in the survey. Most
      mothers were white, married, and had attended college. After entering control
      variables (income, work status, and perceived stress) in regression analyses,
      mothers' overall health behaviors were significantly related to total child
      behavioral/emotional problems. These preliminary findings suggest that the health
      behaviors of mothers may be related to children's mental health, but the
      direction of the relationship should be tested further in longitudinal research.

PMID- 8557836
TI  - Pediatric compliance and the roles of distinct treatment characteristics,
      treatment attitudes, and family stress: a preliminary report.
AB  - Much research and clinical practice derives from the assumption that there is a
      set of psychological-social variables that commonly influence medical
      (non)compliance. This assumption may lead to overly general strategies for
      managing specific illnesses in children with chronic illness. With this concern
      in mind, a study was made of health provider ratings of compliance, treatment
      attitudes, and illness-related family stress for three pediatric cohorts (N = 75,
      ages 8 to 20 years): boys with hemophilia (n = 31), sickle cell disease (n = 22),
      or asthma (n = 22). Between-group differences were found on compliance and
      treatment attitudes (p < .05), with patients with sickle cell demonstrating
      greater treatment cooperation than their counterparts and boys with hemophilia
      expressing more positive outlooks on medical advice and about health outcomes
      (Newman-Keuls test, p < .05). Positive treatment attitudes were associated with
      specific compliance behaviors for boys with hemophilia (p < .045) but not for
      other groups.

PMID- 8557837
TI  - Dyslexia: empowering parents to become their child's educational advocate.

PMID- 8557838
TI  - Developmental and behavioral issues in childhood injury prevention.
AB  - Injuries are the most important cause of mortality, morbidity, and disability
      during childhood and adolescence. Injuries with the greatest impact on the
      behavioral and emotional development of the child are head injuries and severe
      burns, both of which can markedly impact on subsequent development. Important
      risk factors for injury are gender, age, socioeconomic status, developmental
      status, behavior problems, substance abuse by parent and adolescent, and parents'
      perceptions of injury risk. These factors interact to increase or decrease the
      risk of injury in any given child and are much more meaningful than the futile
      search for the "accident-prone" individual. These factors must be taken into
      consideration when planning intervention strategies to ensure optimal
      effectiveness of intervention.

PMID- 8557839
TI  - Expressive language delay in a toddler.

PMID- 8557840
TI  - Evidence to support the distal vagal ganglion as the origin of C cells of the
      ultimobranchial gland in the chick.
AB  - Formation and development of the ultimobranchial anlage were studied in chicken
      embryos by immunohistochemistry with the antibodies to class III beta-tubulin,
      TuJ1, human leukemic cell-line (HNK-1), and protein gene product (PGP) 9.5, all
      of which recognized neurons. Medial to the fourth aortic arch, the
      ultimobranchial anlage was formed by the extension of the ventral portion of the
      fourth pharyngeal pouch at 4.5 days of incubation. At 5 days of incubation, TuJ1
      immunoreactive cells with long cell processes began to enter the ultimobranchial
      anlage, which displayed a follicle structure. At 6 days of incubation, numerous
      neuronal cells that were continuous with the distal vagal ganglion (nodose
      ganglion) and expressed immunoreactivity for TuJ1, HNK-1, and PGP 9.5 were found
      to be in direct contact with the peripheral portion of ultimobranchial anlage.
      The TuJ1 antibody reacted only with the neuronal cells, whereas the HNK-1 and PGP
      9.5 antibodies reacted with both endodermal epithelial cells and the neuronal
      cells in the ultimobranchial anlage. Subsequently, the ultimobranchial anlage
      rapidly increased in size; the follicle wall was thickened and a central cavity
      disappeared. The TuJ1-immunoreactive cells were distributed throughout the
      ultimobranchial parenchyma in 7-day-old embryos. The neuronal cell streams from
      the distal vagal ganglion to the ultimobranchial anlage were still prominent at 8
      days of incubation. Almost all parenchymal cells of the ultimobranchial glands
      were intensely immunoreactive for TuJ1, HNK-1, and PGP 9.5 between 10 and 16 days
      of incubation. These results indicate that the neuronal cells from the distal
      vagal ganglion enter into the ultimobranchial anlage and give rise to C cells,
      i.e., C cells differentiate along the neuronal lineage. During embryonic
      development, C cells of the chick ultimobranchial glands transiently express a
      number of neuronal properties.

PMID- 8557841
TI  - The septal complex of the telencephalon of the lizard Podarcis hispanica. I.
      Chemoarchitectonical organization.
AB  - In this paper we study the septal complex architecture in the lizard Podarcis
      hispanica (Lacertidae). Histochemical and immunohistochemical techniques were
      used to define the distribution of zinc (Timm stain), acetyl cholinesterase
      (AChase), gamma-aminobutyric acid (GABA), tyrosine hydroxylase (TH), dopamine
      (DA), serotonin (5-HT), and two neuropeptides: leu-enkephalin (L-ENK) and
      substance P (SP). These reactions delineate a coherent map of nine septal nuclei
      that are named with a topographical nomenclature: anterior, lateral,
      ventromedial, medial, dorsolateral, ventrolateral, and dorsal septal nuclei,
      nucleus septalis impar, and nucleus of the posterior pallial commissure. The
      anterior septal nucleus is characterized by intense reaction for zinc and the
      presence of fibers immunoreactive for GABA, 5-HT, and L-ENK, which form
      pericellular nests. The lateral septal nucelus shows intense reaction for zinc, a
      high density of GABA-immunoreactive cells, and L-ENK-immunoreactive fibers
      forming basketlike figures around unstained somata. The ventromedial septal
      nucleus shows intense AChase reactivity, a dense network of 5-HT-immunoreactive
      fibers, and virtually no labeling for the other histochemical stains. The medial
      septal nucleus is defined by heavy reactivity for zinc, dense DA/TH and L-ENK
      innervations, and the presence of L-ENK-immunoreactive cells. The dorsolateral
      septal nucleus shows intense AChase staining in the neuropile and a dense network
      of fibers immunoreactive for 5-HT and DA/TH, but it shows low staining for zinc.
      The ventrolateral septal nucleus shows L-ENK-immunoreactive cells and a dense L
      ENK innervation, but low reactivity for zinc. The dorsal septal nucleus,
      intermingled with the fimbrial fibers, shows a dense population of GABA
      immunoreactive cells and terminals, but it is unreactive for zinc. Two
      subdivisions can be established in this dorsal septal nucleus: the dorsal part,
      intensely reactive for AChase and innervated by 5-HT fibers, and the central
      part, which shows L-ENK-immunoreactive neurons and fibers without reactivity for
      either AChase or 5-HT. The nucleus septalis impar, traversed by the fibers of the
      anterior pallial commissure (mildly reactive for zinc), shows reaction for AChase
      but low (if present) reactivity for the remaining markers. The nucleus of the
      posterior pallial commissure shows a generally low reactivity for the
      histochemical reactions employed. The distribution of these markers is similar to
      that found in other squamate reptiles and allows for a direct comparison with the
      septal formation of mammals. Such a comparison reinforces the view that the
      limbic system has undergone a conservative evolution within vertebrates.

PMID- 8557842
TI  - Intrinsic circuit organization of the major layers and sublayers of the
      dorsolateral prefrontal cortex in the rhesus monkey.
AB  - Intrinsic connections are likely to play important roles in cognitive information
      processing in the prefrontal association cortex. To gain insight into the
      organization of these circuits, intracortical connections of major laminar and
      sublaminar divisions were retrogradely labeled in Walker's area 9 and 46 in
      rhesus monkeys by using cholera toxin (B-subunit) conjugated to colloidal gold.
      Microinjections placed within particular cortical laminae produced unique
      patterns of retrograde labeling. Injections in layers II/III yielded labeling
      which was laterally widespread (2-7 mm) in supragranular layers, and more
      narrowly focused, i.e., conforming to a column, in layers IV-VI. In contrast,
      local circuits associated with layers IV and Vb displayed a regular, cylindrical
      organization, whereas intrinsic connections of layer Va were laterally extensive
      (3-5 mm) in layers III and Va. Finally, injections in layer VI gave rise to a
      narrow column of cell labeling traversing all layers, augmented by laterally
      extensive labeling (approximately 7 mm) in layer VI. The intrinsic connections of
      the prefrontal cortex were arrayed within mediolaterally elongated stripes which
      were often distributed asymmetrically in either the medial or lateral direction.
      In addition, labeled cells within these mediolaterally oriented fields were
      frequently grouped within discrete clusters or narrow bands. The intrinsic
      connections identified in this study differ from the local circuits of
      corresponding layers reported for primary visual cortex; the unique intrinsic
      wiring diagram of the prefrontal cortex may be related to its specialized
      cognitive and mnemonic functions.

PMID- 8557843
TI  - Cajal-Retzius neurons in human cerebral cortex at midgestation show
      immunoreactivity for neurofilament and calcium-binding proteins.
AB  - Along with subplate neurons, Cajal-Retzius cells (CRc) are the first neurons to
      be generated in the cortical anlage. Studies of their chemical content, such as
      neurofilament and calcium-binding proteins, might give indications on their role
      in cortical development at midgestation in human fetuses (20-24 gestation weeks),
      when the CRc are morphologically mature. Cajal-Retzius cells were immunolabeled
      with antibodies to subunits of neurofilament proteins SMI31 and SMI32. The SMI32
      antibodies (directed against the nonphosphorylated epitope) specifically labeled
      the CR cell bodies, dendrites, and proximal axons in a Golgilike fashion.
      Specific acetylcholinesterase activity is known to be typical of all the CRc, and
      double labeling for SMI32 immunoreactivity and acetylcholinesterase
      histochemistry demonstrated that all the CRc exhibited SMI32 immunoreactivity.
      The SMI31 antibodies (directed against the phosphorylated epitope) exclusively
      labeled the CRc axons, forming a dense positive network in the deep one-half of
      layer 1. This plexus was much denser than the one described with the Golgi method
      (Marin-Padilla, 1990: J. Comp Neurol 239:89-105). Calbindin D28k, parvalbumin,
      and calretinin immunoreactivities were visualized in the CRc. Double-labeling
      experiments showed that most of the CRc contained both calbindin and calretinin
      and sometimes parvalbumin. These colocalizations revealed a chemical
      heterogeneity within the CRc population even though they were described as
      morphologically homogeneous. These colocalizations of calcium-binding proteins in
      the CRc differed from the other nonpyramidal cortical neurons where calbindin,
      calretinin, and parvalbumin are contained in different (mutually exclusive)
      neuronal populations. Based on the morphological features and differential
      chemical contents described for the CRc, different hypotheses on their possible
      role and fate are discussed.

PMID- 8557844
TI  - Reconstitution of the rat olfactory epithelium after methyl bromide-induced
      lesion.
AB  - The olfactory epithelium and its neuronal population are known to have a
      substantial capacity to recover after either direct injury or damage to the
      olfactory nerve. However, the mechanisms underlying that capacity for recovery,
      and indeed the limits on the recovery process, are not well understood. The aim
      of this study is to describe in detail the way in which the olfactory epithelium
      reconstitutes after direct injury. Adult male rats were exposed to 330 ppm methyl
      bromide (MeBr) gas for a single 6-hour period. The exposure destroys all of the
      neurons and sustentacular cells in over 95% of the olfactory epithelium of food
      restricted rats and in over 90% of the epithelium in ad-libitum-fed rats of the
      same weight, yet substantial recovery of the olfactory epithelium occurs. In
      response to the lesion, cellular proliferation increases markedly beginning
      between 24 and 48 hours, peaks at 1 week, and persists at levels higher than the
      control level for more than 4 weeks after MeBr exposure. Even though
      proliferation accelerates promptly, the beginning of neuronal reconstitution is
      delayed; only a few immature neurons are observed 3 days after the lesion, yet
      they reappear in large numbers by the end of the first week. The first mature
      neurons emerge between 7 and 14 days after lesion and increase to near normal
      numbers by 4-6 weeks. In association with the restoration of the neuronal
      population, basal cell proliferation returns to control levels between 4 and 6
      weeks after damage. Likewise, sustentacular cells, identifiable by
      anticytokeratin 18 labeling, reappear rapidly and reform a distinct lamina in the
      superficial aspect of the epithelium. They closely resemble their counterparts in
      control epithelium with regard to disposition and shape by 3 weeks after lesion
      and with regard to expression of olfactory-specific cytochrome P450s by 8 weeks.
      Thus, most areas of the epithelium are restored to a near normal appearance and
      cellular composition by the end of 8 weeks, suggesting that the MeBr paradigm for
      lesioning the epithelium offers significant advantages over techniques such as
      Triton X-100 or ZnSO4 irrigation. However, not all measures of epithelial status
      are normal even at 8 weeks. Immature neurons remain slightly more numerous than
      normal at this time. Furthermore, some areas of the olfactory epithelium do not
      recover after MeBr lesion and are replaced by respiratory epithelium.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8557845
TI  - GABAA-receptor heterogeneity in the adult rat brain: differential regional and
      cellular distribution of seven major subunits.
AB  - GABAA-receptors display an extensive structural heterogeneity based on the
      differential assembly of a family of at least 15 subunits (alpha 1-6, beta 1-3,
      gamma 1-3, delta, rho 1-2) into distinct heteromeric receptor complexes. The
      subunit composition of receptor subtypes is expected to determine their
      physiological properties and pharmacological profiles, thereby contributing to
      flexibility in signal transduction and allosteric modulation. In heterologous
      expression systems, functional receptors require a combination of alpha-, beta-,
      and gamma-subunit variants, the gamma 2-subunit being essential to convey a
      classical benzodiazepine site to the receptor. The subunit composition and
      stoichiometry of native GABAA-receptor subtypes remain unknown. The aim of this
      study was to identify immunohistochemically the main subunit combinations
      expressed in the adult rat brain and to allocate them to identified neurons. The
      regional and cellular distribution of seven major subunits (alpha 1, alpha 2,
      alpha 3, alpha 5, beta 2,3, gamma 2, delta) was visualized by immunoperoxidase
      staining with subunit-specific antibodies (the beta 2- and beta 3-subunits were
      covisualized with the monoclonal antibody bd-17). Putative receptor subtypes were
      identified on the basis of colocalization of subunits within individual neurons,
      as analyzed by confocal laser microscopy in double- and triple-immunofluorescence
      staining experiments. The results reveal an extraordinary heterogeneity in the
      distribution of GABAA-receptor subunits, as evidenced by abrupt changes in
      immunoreactivity along well-defined cytoarchitectonic boundaries and by
      pronounced differences in the cellular distribution of subunits among various
      types of neurons. Thus, functionally and morphologically diverse neurons were
      characterized by a distinct GABAA-receptor subunit repertoire. The multiple
      staining experiments identified 12 subunit combinations in defined neurons. The
      most prevalent combination was the triplet alpha 1/beta 2,3/gamma 2, detected in
      numerous cell types throughout the brain. An additional subunit (alpha 2, alpha
      3, or delta) sometimes was associated with this triplet, pointing to the
      existence of receptors containing four subunits. The triplets alpha 2/beta
      2,3/gamma 2, alpha 3/beta 2,3/gamma 2, and alpha 5/beta 2,3/gamma 2 were also
      identified in discrete cell populations. The prevalence of these seven
      combinations suggest that they represent major GABAA-receptor subtypes. Five
      combinations also apparently lacked the beta 2,3-subunits, including one devoid
      of gamma 2-subunit (alpha 1/alpha 2/gamma 2, alpha 2/gamma 2, alpha 3/gamma 2,
      alpha 2/alpha 3/gamma 2, alpha 2/alpha 5/delta).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8557846
TI  - Dark-rearing changes dendritic microtubule-associated protein 2 (MAP2) but not
      subplate neurons in cat visual cortex.
AB  - Sensory-dependent modification of cortical morphology is one component of the
      cortical plasticity that occurs during the critical period for ocular dominance
      changes. In this study, we used dark-rearing to examine the sensory dependency of
      subplate neuron death and the quantity of microtubule-associate protein 2 (MAP2)
      positive dendrites. Kittens reared in total darkness until the peak of the
      critical period had fewer laterally extended MAP2-positive dendrites than age
      matched normal kittens. This reduction was found in layer IV but not in layer V.
      Subsequent exposure to light for 10 days after dark-rearing was sufficient to
      bring the number of MAP2-positive dendrites to the normal level. Contrarily, dark
      rearing did not prevent subplate neurons from dying. Exposure to light after dark
      rearing did not increase the number of potential dying neurons. These results
      show that the quantity of MAP2-positive dendrites is sensory-dependent; however,
      the death of the subplate neurons is not. Therefore, the death of subplate
      neurons is probably not directly involved in sensory-dependent modifications of
      synaptic connections. The possible involvement of laterally extended MAP2
      dendrites in visual plasticity is discussed.

PMID- 8557847
TI  - Human orbitofrontal cortex: cytoarchitecture and quantitative immunohistochemical
      parcellation.
AB  - The primate orbitofrontal cortex is a component of the paralimbic cortical "belt"
      and consists of several distinct areas. It is involved in high order association
      functions that include the integration of emotion, behavior, and various sensory
      processes. To define the cyto- and chemo-architectonic organization of the human
      orbitofrontal cortex, we have used antibodies to the nonphosphorylated
      neurofilament triplet protein and to the calcium-binding proteins parvalbumin and
      calretinin. Immunohistochemistry revealed labeling patterns corresponding to the
      cytoarchitecture defined by Nissl preparations. Neurofilament protein
      immunoreactive pyramidal neurons were located only in layers V-VI in the
      agranular posterior orbitofrontal cortex, whereas they were distributed in both
      layers III and V-VI in the anteromedial and anterolateral granular regions. The
      intermediate dysgranular portion of the orbitofrontal cortex represented a
      transition zone with a progressive decrease in layer III labeled pyramidal cell
      numbers posteriorly. The distribution of parvalbumin- and calretinin
      immunoreactive interneurons was more homogeneous, although the posteromedial
      region and the cortex of the inferior rostral sulcus had slightly lower
      parvalbumin-positive neuron counts than the other orbitofrontal areas.
      Parvalbumin immunoreactivity in the neuropil exhibited a high degree of regional
      specialization in that it was consistently less intense in the cortex of the
      intermediate and posterior part of the gyrus rectus, whereas the other
      orbitofrontal areas had a very dense neuropil staining in layers III to V. Also,
      there was a dense plexus of parvalbumin-immunoreactive fibers restricted to layer
      I in the posterolateral orbitofrontal cortex, and patches of neuropil staining in
      layer III of the inferior rostral sulcus. These region-specific neuropil staining
      patterns may correspond to the distribution of parvalbumin-immunoreactive
      thalamocortical projections to distinct domains of the orbitofrontal cortex. This
      regional parcellation of the human orbitofrontal cortex as defined by specific
      neuronal markers, may represent an anatomical substrate for the localization of
      the various functions attributed to this poorly understood cortical region.

PMID- 8557848
TI  - Increase in alpha-CGRP and GAP-43 in aged motoneurons: a study of peptides,
      growth factors, and ChAT mRNA in the lumbar spinal cord of senescent rats with
      symptoms of hindlimb incapacities.
AB  - Sprague-Dawley rats develop progressive motor dysfunctions during the third year
      of life. We use this as a model to examine possible neuronal mechanism(s) that
      may cause motor impairments occuring during aging. In this study we have used
      indirect immunofluorescence histochemistry (IF) and in situ hybridization
      histochemistry (ISH) to study quantitatively and qualitatively the staining
      pattern and mRNA expression of calcitonin gene-related peptide (alpha-CGRP),
      growth-associated protein 43 (GAP-43), and acidic fibroblast growth factor (aFGF)
      in spinal lumbar motoneurons of young adult (2-3 months) and aged (30 months)
      Sprague-Dawley rats. In addition, mRNAs encoding choline acetyltransferase
      (ChAT), beta-CGRP, and cholecystokinin (CCK) were analyzed. All aged rats used in
      this study disclosed symptoms of hindlimb incapacity, ranging from mild weight
      bearing insufficiency to paralysis of the hind limbs. The symptoms were confined
      to the musculature of the hindlimb and hip regions. Only a small number
      (approximately 15%) of the large motoneurons that innervate the hindlimb muscles
      were lost in those aged rats that had clinical symptoms of hindlimb motor
      incapacities. The remaining motoneurons expressed ChAT mRNA at levels similar to
      those of young adult rats. The vast majority of these motoneurons showed
      increased mRNA levels for alpha-CGRP and GAP-43. Aged motoneurons contained more
      CGRP like immunoreactivity (LI), but the number of immunoreactive neurons was
      smaller than in adult rats. GAP-43-LI could be detected in motoneurons in aged,
      but not in adult, rats. GAP-43-LI was always colocalized with CGRP-LI in aged
      motoneurons. Studies of individual aged rats revealed that the increase of GAP-43
      mRNA-positive cell bodies occurred in cases with the most severe clinical
      symptoms, whereas the increase in alpha-CGRP was even evident in rats with mild
      symptoms. No alterations in content of aFGF-LI or aFGF mRNA could be detected in
      the aged rat, and the content of CCK and beta-CGRP mRNAs was also normal. The
      usefulness of this rat model for studies of neuromuscular aging and possible
      functional roles for GAP-43 and CGRP in plastic and regenerative processes during
      aging are discussed.

PMID- 8557849
TI  - Ascending projections of the posterior nucleus of the hypothalamus: PHA-L
      analysis in the rat.
AB  - With the exception of a report by R.B. Veazey, D.G. Amaral, and W.M. Cowan (1982,
      J. Comp. Neurol. 207:135-156) that examined the projections of the posterior
      hypothalamic area in the monkey by using the autoradiographic technique, the
      ascending projections of the posterior nucleus (PH) of the hypothalamus have not
      been systematically examined in any species. The present report describes the
      ascending projections of PH in the rat by using the anterograde anatomical
      tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L). The major ascending route for
      PH fibers is the medial forebrain bundle. PH fibers project densely to several
      subcortical and cortical sites. The subcortical sites are the
      subthalamus/hypothalamus (zona incerta, the supramammillary nucleus, lateral,
      perifornical, dorsal, and anterior nuclei/areas), the thalamus (lateroposterior,
      laterodorsal, parafascicular, reuniens, paraventricular, central medial,
      paracentral, central lateral and intermediodorsal nuclei), the amygdala (central,
      lateral, and medial nuclei), the septal area (bed nucleus of stria terminalis,
      medial and lateral septum), and the basal forebrain (horizontal/vertical limbs of
      diagonal band nuclei and lateral preoptic area). The cortical sites are the
      perirhinal, insular, frontal (lateral agranular), prelimbic, and infralimbic
      cortices. The diversity of PH projections to subcortical and cortical "limbic
      related" sites and to several structures with direct input to the hippocampus
      (supramammillary nucleus, reuniens, paraventricular and laterodorsal nuclei of
      the thalamus, medial and lateral septum, and perirhinal cortex) suggest that the
      PH may serve a critical role in various components of emotional behavior,
      including mnemonic processes associated with significant emotional events.

PMID- 8557850
TI  - Effects of the horn fly (Diptera: Muscidae) on physiological and nutritional
      responses of beef steers: continuous fly population levels.
AB  - Twenty-four Hereford-Angus crossbred beef steers were exposed to 0, 75, 150, and
      225 horn flies, Haematobia irritans (L.), per head under controlled environmental
      conditions. The physiological and nutritional indices of all steers were recorded
      during a 14-d infestation period. Overall rectal temperature increased in steers
      exposed to 225 H. irritans was per head. Feed intake and nitrogen consumption by
      steers exposed to 225 H. irritans was lower than uninfested steers during the
      first 4 d. Overall serum cortisol was lower in steers exposed to 150 or 225 H.
      irritans per head compared with unexposed steers. Compared with unexposed steers,
      packed cell volume (percentage) was lower in steers exposed to 150 H. irritans on
      days 4, 7, and 14, lower in steers exposed to 225 H. irritans on days 7 and 14,
      and lower in steers exposed to 75 H. irritans on day 14. Blood urea nitrogen
      (BUN) was higher on day 1 in steers exposed to 75 H. irritans per head compared
      with uninfested steers, whereas BUN was lower in 225 H. irritans-exposed steers
      on days 7, 10, and 14 when compared with uninfested steers. Our data, in
      conjunction with previously published data, suggest that rectal temperature
      increases in beef steers exposed to > 150 H. irritans per head, and water
      consumption and urine production increases at infestation levels > 225 H.
      irritans per per head. Our data were unable to resolve H. irritans effects on
      steer heart rate, respiration rate, urinary nitrogen excreted, nitrogen retained,
      and serum cortisol levels.

PMID- 8557851
TI  - Development of insecticide resistance in Piophila casei (Diptera: Piophilidae)
      strains selected with low doses of deltamethrin.
AB  - Two populations of the cheese skipper, Piophila casei (L.), were sampled. The 1st
      was from a sheep farm where no chemical was ever applied; the 2nd was present in
      a ham factory where chemical treatment with pyrethroids was applied in the past
      against house flies, Musca domestica L., and Dermestid beetles. A substantial
      difference between their resistance to deltamethrin was observed (LC50 = 11.56
      versus 68.08 micrograms/cm2 for females and 1.11 versus 4.20 micrograms/cm2 for
      males, respectively). Laboratory strains were established from both populations
      and were selected at constant rates for up to 20 generations (2, 4, and 7.3 ppm
      for the strains derived from the 1st population and 40 ppm for that selected from
      the 2nd population). Males and females of both strains showed an increase in LC50
      (tested at the 5th and 19th or 10th generation), except when females were
      selected at the lowest rate (2 ppm). At the end of the trial, slopes of logit
      regressions were substantially steeper in strains selected at higher rates,
      suggesting that the effect of the insecticide was to reduce resistance variance.
      Crosses between unselected and selected strains were done. Results of survival
      analysis in F1 hybrids were analogous for males and females and were similar in
      both reciprocal crosses. LC50S were intermediate between those of the parental
      strains.

PMID- 8557852
TI  - Vasculitis.
AB  - Many cutaneous and systemic disorders are associated with inflammation and
      necrosis of blood vessels. Several classifications of vasculitis have been used.
      Internists tend to utilize the classification of Fauci with modifications such as
      those by Cupps. Gibson and Ryan, who are dermatopathologists, have classified
      vasculitis based on vessel size, leukocyte type, and presence of granulomas. A
      more recent classification has been developed by Jennette, a pathologist, and
      colleagues. The etiology of vasculitis is varied; it includes bacteria, viruses,
      chemicals, autoimmune disease, malignancy and abnormal exogenous and endogenous
      proteins. Leukocytoclastic vasculitis can be experimentally reproduced by the
      Arthus phenomenon. IgM and C3 are found in cutaneous blood vessels and associated
      with circulating immune complexes. CH50, C3 and C4 may be reduced in serum.
      Increased incidence of nasal carriage of staphylococci is associated with higher
      relapse rates in Wegener's granulomatosis and toxic shock syndrome toxin from
      staphylococci is associated with the Kawasaki syndrome. Additionally, at least
      four systemic vasculitic drug reactions can be confirmed with patch testing.
      Antineutrophil cytoplasmic antibodies (ANCA) are found in association with
      certain systemic vasculitides. These may be tested with indirect
      immunofluorescence and enzyme linked immunosorbent assays (ELISA) with
      radioimmunoassays. Originally cytoplasmic ANCA (cANCA) was identified with
      proteinase 3 as the antigen and perinuclear ANCA (pANCA) was related to
      myeloperoxidase. While cANCA is very specific for proteinase 3, pANCA is
      associated with a number of antigens other than myeloperoxidase. pANCA is found
      with alcohol fixed but not formalin-fixed neutrophils. cANCA is particularly
      sensitive and specific for Wegener's granulomatosis and predicts prognosis and
      response to therapy. pANCA is not so specific and is associated with a number of
      other vasculitic syndromes. Cutaneous vasculitis is managed primarily with
      colchicine, dapsone and prednisone, with recent studies indicating that there may
      be a synergistic effect of pentoxifylline with dapsone. Systemic vasculitis
      involves treatment with various agents. Recently it has been observed that co
      trimoxazole (trimethoprim/sulfamethoxazole) is useful in many cases of Wegener's
      granulomatosis along with other more toxic chemotherapeutic agents.

PMID- 8557853
TI  - The porphyrias: a brief overview based on 25 years of experience (1969-1994) by
      the Department of Dermatology of the Hospital Clinic and Faculty of Medicine of
      Barcelona, Spain.
AB  - The porphyrias are uncommon diseases caused by enzymatic deficiencies in the heme
      pathway. In the 25 year period 1969-1994, the Department of Dermatology of the
      Hospital Clinic of Barcelona has been able to study 793 cases of porphyria (724
      cases of PCT, 27 of EPP, 26 of PV, 5 of CEP, 5 of HEP, 5 of AIP, 1 of HCP).
      Homozygous expression of an enzymatic deficiency in the heme pathway produces
      severe disease. Commonly, clinical manifestations appear in the homozygous state
      (the autosomal recessive porphyrias). However, homozygous forms of autosomal
      dominant porphyrias may occur exceptionally. Moreover, there are cutaneous
      porphyrias whose clinical manifestations do not permit dermatologists to classify
      them clearly into one of the well-defined syndromes. These uncommon and atypical
      forms are difficult to recognize without biochemical and enzyme studies. The
      porphyrias have a wide clinico-biochemical spectrum, including a large proportion
      of well defined diseases. Nevertheless, atypical forms occur and may be difficult
      to evaluate. It is important to note the genetic heterogeneicity of porphyrias,
      which accounts for the varying phenotypic expression.

PMID- 8557854
TI  - Studies of patients with anti-epiligrin cicatricial pemphigoid.
AB  - We have recently identified patients with a form of cicatricial pemphigoid who
      have IgG anti-basement membrane autoantibodies directed against epiligrin, a
      laminin isoform closely related if not identical to laminin 5. These patients'
      autoantibodies bind the lower lamina lucida of human epidermal basement membrane
      and immunoprecipitate this laminin isoform from extracts and media of
      biosynthetically radiolabeled human keratinocytes. Immunoblot studies show that
      these patients' autoantibodies specifically bind the alpha subunit of this
      laminin (i.e., laminin subunit alpha 3). We have found no evidence of these
      autoantibodies in normal volunteers or patients with other bullous skin diseases
      (including those with other forms of CP). These studies have identified a group
      of patients with an acquired, autoimmune, subepidermal bullous disorder who have
      disease-specific autoantibodies directed against the alpha subunit of
      epiligrin/laminin 5. These findings correlate with prior reports showing that a
      monoclonal antibody directed against this laminin subunit induces detachment of
      keratinocytes from extracellular matrix in vitro as well as epidermis from human
      skin in situ. Together, these findings suggest that this laminin mediates
      attachment of basal keratinocytes to epidermal basement membrane and that
      autoantibodies directed against it may be pathogenic. Moreover, recent studies
      showing that subunits of this laminin isoform are mutated in some patients with
      Herlitz's junctional epidermolysis bullosa indicate that acquired or inherited
      abnormalities in this adhesion ligand are associated with skin diseases
      characterized by separation of epidermis from epidermal BM.

PMID- 8557855
TI  - What is the epidermal intercellular cement and why is it important?

PMID- 8557856
TI  - Immunologic roles of keratinocytes: expression of HLA-DR and ICAM-1 on cultured
      human keratinocytes and their influences on the alloimmune response.

PMID- 8557857
TI  - Angiogenesis.
AB  - The formation of new blood vessels, angiogenesis, is a complex process which is
      central to normal development and homeostasis. However, uncontrolled angiogenesis
      plays a critical role in both inflammatory and neoplastic disorders. Our
      understanding of angiogenesis has expanded greatly over the past two decades due
      to the development of in vivo and in vitro models to study this important
      process. A variety of cytokines and growth factors have been shown to induce new
      blood vessel formation in vivo, and in vitro studies have been able to define
      whether agents have direct or indirect effects upon vascular endothelial cells.
      Our improved understanding of the mechanisms which regulate angiogenesis has now
      created important opportunities for the development of new therapies for the
      treatment of inflammatory and neoplastic skin disease.

PMID- 8557858
TI  - The epidemiology of non-melanoma skin cancer: who, why and what can we do about
      it.
AB  - Non-melanoma skin cancer (NMSC) comprised of basal cell carcinoma (BCC) and
      squamous cell carcinoma (SCC) are the most common cancers in humans in many
      countries. Sunlight plays a major part in the development of these tumours which
      appear predominantly on areas of the most frequently exposed skin. The site
      distribution for BCC and SCC is not the same, with SCC being most common on the
      sites of very heavy exposure and BCC becoming more common on areas of only
      moderate exposure, e.g. upper trunk in men and women and lower leg in women.
      Incidence rates of NMSC, where they are being recorded, show rises over time.
      Mortality rates, on the other hand, have been dropping most of this century until
      they have been levelling out recently. The case fatality rate due to SCC appears
      to be between 1-2%. The malignant transformation rate of actinic keratoses to SCC
      appears to be very low. Studies on similar populations at different latitudes
      allow estimates to be made of increases which might occur with increasing
      exposure to ultraviolet radiation (UVR) over a life time. These have been used to
      estimate the possible increases in NMSC due to stratospheric ozone depletion.
      Finally, recent studies on the reduction of existing actinic keratoses and
      prevention of new ones with regular use of sunscreen augurs well for prevention
      of NMSC in the future.

PMID- 8557859
TI  - Alopecia areata in Korea (1982-1994).
AB  - I clinically studied 905 patients with alopecia areata (AA) who visited the
      Department of Dermatology, College of Medicine, Chung Ang University, from
      January of 1982 to February of 1994. The purpose of the study was to evaluate the
      clinical manifestations and compare the effects of treatment with intralesional
      injection of triamcinolone acetonide suspension and immunotherapy with
      dinitrochlorobenzene (DNCB) or diphenylcyclopropenone (DPCP). The results were as
      follows: 1) The incidence of AA among all out-patients (59,970) was 1.5% (905
      cases), and the ratio of males to females was 1.3:1 (512:393). 2) The age
      distribution showed high incidences in the third (41.8%) and fourth decades
      (20.0%). 3) The family history was contributory in 104 cases (11.5%). 4) The
      relapse rate was 17.5% (158 cases). 5) Almost half of the patients had a solitary
      lesion (408 cases, 46.7%). 6) The most common site of predilection was the
      occipital region of the scalp in both male and female patients. 7) Associated
      diseases were seborrheic dermatitis, atopic dermatitis, hepatitis, hypertension,
      open heart surgery, thyroid disease, pulmonary disease, and vitiligo in order of
      frequency. 8) The effect of treatment on the patients who had bald patches less
      than 50 cm2 was not significantly statistically different between intralesional
      injection of triamcinolone acetonide and immunotherapy with DNCB or DPCP. 9) In
      cases with bald areas more than 50 cm2, including alopecia totalis and
      universalis, DNCB or DPCP immunotherapy showed better therapeutic effects than
      did intralesional injection of triamcinolone acetonide.

PMID- 8557860
TI  - Iontophoresis for enhancing penetration of dermatologic and antiviral drugs.
AB  - Iontophoresis is the process of introducing ionic drugs into the body for
      therapeutic purposes. Although iontophoresis has the potential for systemic
      therapy, it has mainly been used for local therapy at body surfaces. Many ionic
      drugs are available including lidocaine, epinephrine, methylprednisolone
      succinate, dexamethasone phosphate, several antivirals, various antibiotics, and
      other specific drugs. The use of an indicated ionic drug by iontophoresis offers
      a broad potential for promoting the development of more effective therapies in
      dermatology. Iontophoresis of ionized drugs provided a 20-60 fold increase in
      penetration over topical application. Iontophoresis for dermatological use
      requires that: a) a charged drug be placed at an electrode having a polarity the
      same charge as the drug, b) the condition or disease under treatment be at or
      near the body surface, and c) a modern, sophisticated source of direct current,
      with appropriate accessories, be used. The current source must have features that
      make it not only effective, but also safe for application to the patient. Modern
      systems for application of drugs by iontophoresis have features that make the
      process simple and efficient for use in practice. Iontophoresis has a long
      history of use, having been suggested for various therapies for many years in
      medicine, physical therapy and dentistry. Pilocarpine iontophoresis is a
      preferred method for cystic fibrosis detection. Also, lidocaine iontophoresis has
      been advocated to anesthetize the tympanic membrane before myringotomy.
      Anesthesia of the skin to a depth of 1.0 cm or more has been reported in double
      blind studies of human volunteers. Local anesthesia by iontophoresis was reported
      to be effective for: 1) cutaneous cutdowns in patients requiring kidney dialysis,
      2) delicate eyelid surgery, as the sole anesthetic, 3) preinjection topical
      anesthesia, and 4) shave biopsies of skin lesions. The use of iontophoresis for
      treating difficult cases of hyperhydrosis is quite popular among dermatologists.
      The present report emphasizes uses of iontophoresis in dermatology and is divided
      into discussion of studies using iontophoresis for postherpetic neuralgia, local
      anesthesia, antiviral therapy, and for corticosteroid therapy of nonspecific
      inflammatory lesions. Over 1250 patients have been treated for postherpetic
      neuralgia by corticosteroid iontophoresis at 6 medical centers with 60-80% of
      patients showing a major therapeutic response with return to a tolerable pain
      level. Double-blind studies of varicella zoster (active and postherpetic) and
      herpes simplex have proven that iontophoresis is a valuable modality for treating
      viral diseases of the skin. Many other uses for iontophoresis have been proposed
      in the literature that involve several hundred research papers, several textbooks
      and many book chapters. Review of the literature supports the concept that
      iontophoresis provides an optimal method for drug application in therapy of
      surface tissues.

PMID- 8557861
TI  - UVB-dependent modulation of epidermal cytokine network: roles in UVB-induced
      depletion of Langerhans cells and dendritic epidermal T cells.
AB  - The epidermis of mice consists of three cellular components, i.e., keratinocytes,
      Langerhans cells (LC), and dendritic epidermal T cells (DETC). Each epidermal
      subpopulation produces a different set of cytokines, thereby forming a unique
      cytokine milieu. These cytokines, in turn, support the survival and growth of LC
      and DETC and regulate their immunological functions. LC and DETC play important,
      but distinct, effector roles in protective immunity against antigens that are
      generated in or penetrate into the epidermis. Acute or chronic exposure of mice
      to ultraviolet B (UVB) radiation is known to impair this cutaneous immunity, as
      evidenced by the failure to induce T cell-mediated immune reactions, by the
      generation of antigen-specific immunological unresponsiveness, and by the
      development of skin cancers. Importantly, these changes are associated with
      reduced densities of LC and DETC in UVB-exposed skin, suggesting that the
      deficiency in these epidermal leukocytes may account for some of the deleterious
      influences of UVB radiation on skin. Here I will review the recent advance in our
      understanding of the mechanisms by which UVB radiation may deplete LC and DETC
      from epidermis. More specifically, I will discuss the following possibilities: a)
      UVB-mediated suppression of the production of relevant growth factors for LC and
      DETC, b) UVB-induced abrogation of surface expression of growth factor receptors,
      and c) UVB-triggered apoptotic cell death in epidermal leukocytes.

PMID- 8557862
TI  - Keratinocyte-derived cytokines and UVB-induced immunosuppression.
AB  - Ultraviolet radiation (UVB) in sunlight is known to have multiple effects on the
      immune system. Evidence suggests that UVB-induced immunosuppression is mediated
      in part by immunosuppressive and immunoregulatory cytokines. Our studies have
      utilized gene-targeted mutant mice to determine key molecular requirements
      essential for the development of UVB-induced immunosuppression. Preliminary
      results from our laboratory suggest that TNF-alpha plays a regulatory role in
      contact hypersensitivity, but is not a crucial factor for UVB-induced
      immunosuppression, and that multiple factors are involved in the induction of UVB
      mediated immunosuppression.

PMID- 8557863
TI  - Transporting critically ill patients.

PMID- 8557864
TI  - Deterioration of respiratory function after intra-hospital transport of
      critically ill surgical patients.
AB  - OBJECTIVE: To evaluate the impact of intra-hospital transport of artificially
      ventilated patients on respiratory function, and to define predictors that may
      allow estimation of the risk of post-transport pulmonary deterioration. DESIGN:
      Prospective observation study. SETTING: Surgical ICU, University Hospital.
      PATIENTS: 49 intra-hospital transports (median Apache-score before transport 21,
      of 28 consecutive patients (all intubated and mechanically ventilated) were
      studied. INTERVENTIONS: 32 transports were destined to the radiology department
      and 17 to the operating theatre. Patients were ventilated during transportation
      with a transport ventilator. MEASUREMENTS AND RESULTS: The base-line condition of
      the patients and any changes of hemodynamic function were noted. Arterial blood
      gases were determined before transport as well as 0.25, 1, 6, 12, and 24 h after
      return of the patient to the ICU. Of the transports 41 (83.7%) resulted in a
      decrease of PO2/FIO2-ratio with a deterioration of more than 20% from baseline in
      21 cases (42.8%). The impairment of respiratory function lasted longer than 24 h
      in 10 subjects (20.4%). Ventilation with positive end-expiratory pressure
      correlated significantly (r = -0.4) with post-transport change of PO2/FIO2-ratio,
      whereas initial FIO2, initial PO2/FIO2-ratio, Apache II-score, patients' age or
      transport time did not distinguish between patients with and without a
      consecutive decrease of pulmonary function. CONCLUSION: Intra-hospital transport
      of ventilated critically ill patients may result in a considerable and long
      standing deterioration of respiratory function. Patients ventilated with positive
      end-expiratory pressure are at an increased risk and the indication for
      procedures away from the ICU has to be weighted carefully in these subjects.

PMID- 8557865
TI  - Transesophageal echocardiographic study of venous air embolism following
      pneumomediastinum in dogs.
AB  - BACKGROUND: Continuous venous air emboli have been detected in the inferior vena
      cava and smaller veins using transesophageal echocardiography in patients with
      positive pressure ventilation and associated pulmonary barotrauma. The authors
      hypothesized that gas entered the venous circulation, following dissection of
      small vessels at several sites in the subcutaneous or retro-peritoneal soft
      tissues. OBJECTIVE: The present study was designed to determine if a comparable
      venous gas embolism occurred in anesthetized dogs, after creation of a
      pneumomediastinum. DESIGN: Using transesophageal echocardiography, we observed 11
      anesthetized dogs mechanically ventilated with positive end-expiratory pressure,
      while mediastinal air was introduced through a catheter at a rate of 0.5
      ml/kg/min. RESULTS: A continuous stream of bubbles appeared in the inferior vena
      cava in 8/11 dogs (73%) after an infusion period of 280 +/- 81 min. A surge of
      bubbles was commonly observed following abdominal massage and was often
      associated with a transient decrease of end-tidal carbon dioxide tensions. In two
      dogs the air infusion rate was reduced to 0.25 mg/kg/min, and bubbles were
      detected in the inferior vena cava for as long as 16 consecutive hours.
      CONCLUSION: We conclude that in anesthetized dogs mechanically ventilated with
      positive end-expiratory pressure, unremitting pneumomediastinum is usually
      followed by continuous venous air embolism. A mechanism hypothesized for venous
      gas entry in the clinical condition of positive end-expiratory pressure
      ventilation with subcutaneous gas is suggested by this model.

PMID- 8557866
TI  - Organ function during early acute renal failure does not predict survival in long
      term intensive care.
AB  - OBJECTIVE: To examine outcome in relation to organ function variables during
      early acute renal failure (ARF). DESIGN: Retrospective inception cohort. SETTING:
      General intensive care unit (ICU). PATIENTS: 69 consecutive ARF cases verified to
      have a creatinine clearance below 50 ml/min with no history of previous renal
      disease. MAIN OUTCOME MEASURE: ICU survival. MEASUREMENTS AND RESULTS: Septic
      severity score (SSS), creatinine clearance, thrombocyte count, bilirubin
      concentration, cardiac inotropic support, PaO2/FIO2 ratio and oliguria were
      measured. No differences related to outcome were observed in patients surviving
      more than 7 days after ARF diagnosis. Patients dying within 7 days of ARF had a
      significantly higher (worse) SSS. Organ dysfunction was established at the time
      of ICU admission in the majority of cases. CONCLUSION: The organ function
      variables tested in this study are of limited predictive value during the early
      stage of ARF.

PMID- 8557867
TI  - Early metabolic treatment after liver transplant: amino acid tolerance.
AB  - OBJECTIVE: We investigated the amino acid (AA) tolerance during Total Parenteral
      Nutrition (TPN) in adult patients undergone liver transplant (LTX). DESIGN: The
      treatment (Glucose and AA), induced on the 2nd postoperative day, was later
      maintained with 27 kcal/kg Ideal Body Weight (IBW) as glucose and 0.12 (12
      patients: protocol #1), 0.18 (10 patients: protocol #2) and 0.25 g nitrogen
      (N)/kg IBW (13 patients: protocol #3) till end of the 6th postoperative day. The
      N intake was sequentially modified in protocol #2 and #3 to increase the supply
      of the amino acid (AA) that resulted in an infusion plasma level below the
      expected "normal" range (between 1 and 1.6 times the overnight fasting plasma
      level of volunteer). PATIENTS: 35 consecutive adult patients without diabetes and
      organ failures for the entire study period. MEASUREMENTS: Plasma AA profile was
      measured before LTX and at the last TPN day under continuous infusion. During #1
      and #2 protocol, many AA resulted below or at the lower range of the norm while,
      during 0.25 gN/kg IBW infusion, the majority of the administered AA significantly
      increased with respect to reference values. Nevertheless, they remained in the
      "normal" plasma range indicating that they were supplied in an optimal amount
      (particularly the aromatic and sulphurated ones, potentially toxic if liver
      function is impaired, and the branched chain AA (BCAA) given at consistent
      dosage: 0.5 g/kg). Arginine resulted significantly increased (Arg: 1.9 times the
      reference) and cystine (Cys: 0.45), serine (Ser: 0.8) and taurine (Tau: 0.85)
      remained significantly lower than "normal" as well as the not administered
      citrulline (Cit: 0.58) and alfa amino butyric acid (Aba: 0.41). The AA (and
      calorie) load almost balanced the N losses during the 5th (0.411 +/- 0.038) and
      6th study day (0.305 +/- 0.019 gN/kg). CONCLUSIONS: 0.25 gN/kg could be
      considered the minimum N load in the uncomplicated adult LTX recipients, for
      reassuring a balanced plasma AA pattern and body N turnover in the early
      postoperative phase.

PMID- 8557868
TI  - Paralysis has no effect on chest wall and respiratory system mechanics of
      mechanically ventilated, sedated patients.
AB  - OBJECTIVE: To evaluate the separate effects of sedation and paralysis on chest
      wall and respiratory system mechanics of mechanically ventilated, critically ill
      patients. SETTING: ICU of the University "La Sapienza" Hospital, Rome. PATIENTS
      AND PARTICIPANTS: 13 critically ill patients were enrolled in this study. All
      were affected by disease involving both lungs and chest wall mechanics (ARDS in 4
      patients, closed chest trauma without flail chest in 4 patients, cardiogenic
      pulmonary oedema with fluidic overload in 5 patients). MEASUREMENTS AND RESULTS:
      Respiratory system and chest wall mechanics were evaluated during constant flow
      controlled mechanical ventilation in basal conditions (i.e. with the patients
      under apnoic sedation) and after paralysis with pancuronium bromide. In details,
      we simultaneously recorded airflow, tracheal pressure, esophageal pressure and
      tidal volume; with the end-inspiratory and end-expiratory airway occlusion
      technique we could evaluate respiratory system and chest wall elastance and
      resistances. Lung mechanics was evaluated by subtracting chest wall from
      respiratory system data. All data obtained in basal conditions (with the patients
      sedated with thiopental or propofol) and after muscle paralysis were compared
      using the Student's t test for paired data. The administration of pancuronium
      bromide to sedated patients induced a complete muscle paralysis without producing
      significant modification both to the viscoelastic and to the resistive parameters
      of chest wall and respiratory system. CONCLUSIONS: This study demonstrates the
      lack of additive effects of muscle paralysis in mechanically ventilated, sedated
      patients. Also in view of the possible side effects of muscle paralysis, our
      results question the usefulness of generalized administration of neuromuscular
      blocking drugs in mechanically ventilated patients.

PMID- 8557869
TI  - Role of systemic inflammatory response syndrome and infection in the occurrence
      of early multiple organ dysfunction syndrome following severe trauma.
AB  - OBJECTIVE: To evaluate the role of infection and systemic inflammatory response
      syndrome (SIRS) on the occurrence of early posttraumatic MODS. DESIGN:
      Retrospective study. SETTING: University Teaching Hospital ICU. PATIENTS: 163
      consecutive patients hospitalized for more than 48 hours following severe trauma.
      MEASUREMENTS AND MAIN RESULTS: The patients were classified into two groups in
      respect to the existence of MODS at day 2. There was 27 patients in the MODS
      group and 136 patients in the no MODS group. The two groups were similar with
      respect to age, sex ratio and Simplified Acute Physiology Score. The MODS group
      had a higher mortality (52 versus 7%), Injury Severity Score (45 +/- 14 versus 31
      +/- 13), hypovolemic shock rate (74 versus 30%), massive volume replacement rate
      (59 versus 6%) and SIRS rate (81 versus 54%) than the no MODS group (P < 0.05).
      The rate of infection was similarly low in the MODS and no MODS group (4 versus
      6% respectively). CONCLUSION: Early MODS is often associated with hypotension and
      massive volume administration but very rarely with infection, despite the high
      rate of SIRS.

PMID- 8557870
TI  - Effect of cyclooxygenase inhibition in a canine model of unilateral pulmonary
      occlusion and reperfusion.
AB  - OBJECTIVE: To assess the effects of the cyclooxygenase inhibitor diclofenac in a
      canine model of pulmonary occlusion and reperfusion of the left lower lobe (LLL).
      DESIGN: Twelve adult beagle dogs (13-17 kg) were randomly assigned to a control
      group (n = 6) and a diclofenac-treated group (n = 6). Animals in the treatment
      group received 20 mg diclofenac sodium/kg as a single dose both before the
      experiment and at the end of surgical preparation; six animals served as
      controls. INTERVENTIONS: In the anesthetized animals, the left upper and middle
      lobes were resected. Circulation and ventilation of the LLL were selectively
      blocked by clamping. Complete occlusion of the LLL (30 min) was followed by
      periods of selective reperfusion (10 min, RP) and combined reperfusion and
      reventilation (120 min, RP/RV). MEASUREMENTS AND RESULTS: Reperfusion of the LLL
      resulted in a significant increase in pulmonary arterial pressure (Ppa) in the
      early RP/RV period as compared to baseline values (25.3 +/- 4.7 vs 15.8 +/- 1.9
      mmHg, p < 0.05, paired t-test). This increase was significantly inhibited in the
      diclofenac-treated animals (17.0 +/- 2.0 mmHg, p < 0.01 vs controls, ANOVA).
      Gravimetrically determined extravascular lung water (EVLW) showed no significant
      difference in the continuously ventilated lobes of the right lung between
      diclofenac-treated animals (3.8 ml/g dry weight) and controls (3.9 +/- 0.9 ml/g
      dry weight) at the end of the experiment. EVLW, however, increased significantly
      in the LLL of control animals after 2 h of combined reperfusion and
      reventilation, whereas this increase was significantly inhibited in the
      diclofenac-treated animals (4.5 +/- 0.7 ml/g dry weight in the diclofenac group
      vs 6.5 +/- 1.3 ml/g dry weight in the control group, p < 0.05). CONCLUSIONS:
      Diclofenac inhibits the increase in both pulmonary arterial pressure and EVLW
      during reperfusion and reventilation of LLL. Thus, these changes appear to be
      mediated by cyclooxygenase metabolites.

PMID- 8557871
TI  - High incidence of hypophosphatemia in surgical intensive care patients: efficacy
      of phosphorus therapy on myocardial function.
AB  - OBJECTIVE: To determine the incidence of hypophosphatemia in a surgical intensive
      care unit and to determine whether or not a phosphorus challenge causes a change
      in cardiac performance in hypophosphatemic patients. DESIGN: Prospective clinical
      study and case reports. SETTING: Surgical intensive care unit in an university
      hospital. PATIENTS: A total of 208 consecutive patients admitted to the surgical
      ICU were evaluated over a 6 months period. INTERVENTIONS: All classical risk
      factors for hypophosphatemia were recorded. A group of 8 moderate or severe
      hypophosphatemic patients were evaluated for hemodynamic data before and after a
      phosphorus load. Glucose phosphate was given over 30 min by the intravenous
      route. Dosage regimen was 0.4 mmol/kg weight for moderate hypophosphatemia and
      0.8 mmol/kg weight for severe hypophosphatemia. RESULTS: Risk factors were
      present in 134 patients and 60 patients were hypophosphatemic (44.8%). Only 3
      risk factors were discriminant for hypophosphatemia: sepsis, diuretics and total
      parenteral nutrition. The mortality was higher in the hypophosphatemic group than
      in the normophosphatemic group (30% versus 15.2%; p < 0.05). Cardiac performance
      improved after phosphatemia normalization in all patients (cardiac index: 3.82 +/
      1.87 versus 4.52 +/- 1.83 1/min.m2; p < 0.01). CONCLUSION: This study underlines
      the high incidence (28.8%) of hypophosphatemia in surgical intensive care
      patients and its association with a high mortality rate (30%). A short course of
      phosphotherapy improves cardiac index (+18%).

PMID- 8557873
TI  - Correction of hypocalcaemia in the critically ill: what is the haemodynamic
      benefit?
AB  - OBJECTIVE: The prevalence of hypocalcaemia is known to be elevated in critically
      ill patients, but the expected benefit from calcium repletion in hypocalcaemic
      patients has not been well defined. The objective of the present study was
      therefore prospective determination of the cardiovascular response to calcium
      administration in critically ill patients with hypocalcaemia. PATIENTS: A total
      of 17 patients found to have ionized hypocalcaemia (Ca2+ < 1.05 mmol/l) from a
      group of 32 patients who were invasively monitored as part of their ICU
      management. INTERVENTION: Slow intravenous injection of 1 g of calcium chloride.
      MEASUREMENTS AND RESULTS: Calcium administration was followed by an increase in
      mean arterial pressure from 77 +/- 8 to 90 +/- 12 mmHg (P < 0.01). There was no
      significant change in cardiac filling pressures or heart rate. Cardiac index and
      systemic vascular resistance increased slightly but not significantly (from 2.67
      +/- 0.92 to 2.81 +/- 1.25 1/min.m2 and from 2133 +/- 647 to 2378 +/- 817
      dynes.s.cm-5 m-2, respectively). Left ventricular stroke work index increased
      from 23 +/- 8 to 32 +/- 13 g.m/m2 (P < 0.01). These changes were maintained for
      60 min. CONCLUSIONS: The correction of hypocalcaemia can result in a significant
      increase in arterial pressure that can persist for at least 1 h. Despite an
      associated improvement in left ventricular function, cardiac index and oxygen
      delivery do not increase significantly.

PMID- 8557872
TI  - Plasma ionized calcium in brain-dead patients.
AB  - BACKGROUND: The mechanism of brain death-induced myocardial dysfunction remains
      debatable. Hypocalcemia is known to induce reversible myocardial dysfunction.
      However, the incidence of hypocalcemia and its effect on myocardial function
      during brain death is unknown. METHODS: In 54 consecutive brain-dead patients, we
      measured plasma total and ionized calcium concentrations, QT and corrected QT
      intervals, and left ventricular ejection fraction area (LVEFa), using
      transesophageal echocardiography. RESULTS: 49 (91%) of brain-dead patients had a
      decrease in total plasma total calcium concentration but only 19 (35%) had a
      decrease in plasma ionized calcium. Corrected total plasma calcium failed to
      predict ionized calcium concentration and QT intervals were not significantly
      different in normo and hypocalcemic patients. The LVEFa was not significantly
      different between normo and hypocalcemic patients (53 +/- 13 versus 50 +/- 20%),
      and no correlation was found between LVEFa and ionized calcium (R = 0.02, NS).
      Hypocalcemic patients required greater doses of dopamine (8.2 +/- 5.2 versus 5.0
      +/- 3.4 micrograms.kg-.min-1, p < 0.02) to maintain arterial pressure.
      Hypocalcemia was associated with a higher volume loading and a lower plasma
      protide concentration which reflected hemodilution. CONCLUSION: A decrease in
      plasma ionized calcium is not frequent, rarely severe, and probably not the main
      mechanism of myocardial dysfunction in brain-dead patients. Hypocalcemic patients
      required higher doses of dopamine, suggesting a decrease in systemic resistance.
      Only direct measurement of ionized calcium can assess plasma calcium ion status
      in brain-dead patients.

PMID- 8557874
TI  - Artificial nutrition support in intensive care units in Spain. Nutritional and
      Metabolic Working Group of the Spanish Society of Intensive Care Medicine and
      Coronary Units (SEMIUC).
AB  - OBJECTIVE: A multicenter survey to study the use of nutritional support in
      patients admitted to the ICU in Spain. DESIGN: The survey was announced during
      the annual Spanish Society of Intensive Care Medicine and Coronary Units (SEMIUC)
      congress meeting. SETTING: Questionnaires designed to determine current clinical
      practice concerning artificial nutrition were sent to the 27 ICU who accepted to
      participate. PATIENTS AND PARTICIPANTS: In each center the 235-question form was
      filled out individually for each patient admitted to the ICU during the month of
      March, 1992. INTERVENTIONS: To validate the study a preliminary pilot surveys
      were conducted to ensure that there was a correct interpretation of the
      questions. The replies were entered into a database for analysis. RESULTS: A
      total of 1261 patients were studied; 33.9% received artificial nutrition (AN).
      The administration of AN was significantly higher in the medical group (44%),
      than in the surgical (37%) and the trauma group (19%). AN was significantly lower
      in patients admitted to private clinic than public institutions (26.7% versus
      34.7%). Among the patients who received AN, enteral nutrition (EN) was
      administered to 59.7% of the patients, total parenteral nutrition (TPN) to 38.5%,
      and peripheral parenteral nutrition (PPN) to 18.2%. Medical patients received
      significantly more EN than surgical and trauma patients. Surgical patients
      received more PN than medical and trauma groups. CONCLUSIONS: Nutritional support
      is a common practice in the treatment of ICU patients in our country. All
      information concerning its use is necessary to optimize it.

PMID- 8557875
TI  - Severe hypotension and coma secondary to unrecognized chronic anterior
      hypophysitis.
AB  - We report an endocrine emergency of a 52-year-old woman with chronic anterior
      pituitary failure of autoimmune origin who developed hypopituitary crisis with
      coma and severe hypotension provoked by an intercurrent bronchopneumonia. At
      admission to the ICU hypopituitarism had not been diagnosed and only Hashimoto's
      thyroiditis with thyroid replacement therapy could be obtained from the patient's
      history. Although the patient presented with somatic signs suggestive of
      hypopituitarism, other causes of coma and hypotension had first to be excluded.
      In the absence of specific treatment the patient died 18 h later with refractory
      cardiac arrest. Diagnosis of acute decompensated chronic hypophyseal failure must
      be considered if hypothermia, refractory hypotension and signs of infection
      without fever are associated with a short stature and the loss of axillary and
      public hair. Waiting for laboratory confirmation of the diagnosis must not delay
      immediate life-saving specific glucocorticoid treatment.

PMID- 8557876
TI  - A comparison of extradural and intraparenchymatous intracranial pressures in head
      injured patients.
AB  - The reliability of extradural pressure measurements for the measure of
      intracranial pressure (ICP) is still controversial. This study was undertaken to
      assess the limits of agreement between extradural and intraparenchymatous
      pressures using respectively the Plastimed extradural sensor and the Camino
      fiberoptic system. The study took place in a neurosurgical intensive care unit.
      Ten head injured patients were included in the study, leading to the comparison
      of 1032 pairs of hourly ICP values. Although the measures were significantly
      correlated, there was no agreement between the two methods of ICP monitoring.
      Extradural pressure was higher than intraparenchymatous pressure (bias 9 mmHg;
      95% confidence interval of bias -9.8 to 27.8 mmHg). The lack of agreement between
      the two methods is probably due to the unreliability of extradural pressure for
      the measurement of ICP.

PMID- 8557877
TI  - Influence of urapidil on cerebrospinal fluid pressure in humans with
      uncompromised intracranial compliance.
AB  - OBJECTIVE: Determine the influence of urapidil on mean lumbar cerebrospinal fluid
      pressure (CSFP), mean arterial pressure (MAP), mean central venous pressure (CVP)
      and heart rate (HR) in awake humans without any evidence of cerebral or
      cardiovascular disease. DESIGN: Open, single-dose volunteer study. INTERVENTIONS:
      CSFP was measured via a spinal needle after i.v. injection of a single dose of
      0.2 mg kg-1 urapidil in six volunteers (2 female, 4 male). MEASUREMENTS AND
      RESULTS: After administration of urapidil, CSFP increased from 7 +/- 1 mmHg to 10
      +/- 1 mmHg (p < 0.05), MAP decreased from 88 +/- 7 mmHg to 74 +/- 5 mmHg (p <
      0.05), CPP decreased from 81 +/- 7 mmHg to 64 +/- 5 mmHg (p < 0.05) and CVP
      decreased from 0 +/- 1 mmHg to -3 +/- 1 mmHg (p < 0.05). CONCLUSION: Our data
      suggest that in humans with presumed normal intracranial compliance the
      administration of urapidil causes a small but statistically significant increase
      in CSFP due to a parallel decrease in MAP.

PMID- 8557878
TI  - Critical care of acute ischemic stroke.

PMID- 8557879
TI  - Imipenem/cilastin dosage during acute renal failure and hemofiltration.

PMID- 8557880
TI  - Primary laryngospasm in a patient with Parkinson's disease: treatment with CPAP
      via minitracheostomy following intubation.

PMID- 8557881
TI  - Inhaled nitric oxide is often efficient in severe ARDS.

PMID- 8557882
TI  - An analysis of memory dysfunction in major depression.
AB  - 15 patients suffering from DSM-III-R major depression were compared with 15 age-,
      sex- and intelligence-matched controls on a battery of memory tests, aimed at
      fractionating memory dysfunction in depression. Patients were unimpaired relative
      to controls on measures of short-term memory, recognition, semantic memory and
      implicit memory. There was no evidence of a hedonic bias in recall of positive
      vs. negatively valenced stimuli, nor was there any correlation between depression
      severity and level of memory impairment. Psychotic patients did not demonstrate
      greater memory impairment relative to nonpsychotic depressed patients. As a
      group, however, depressed patients demonstrated deficits in psychomotor speed and
      in free recall of material (both immediate and delayed). The selective recall
      deficit suggests that material has been encoded but that patients are
      particularly impaired with regard to search and retrieval processes.

PMID- 8557883
TI  - Changes in EEG power density of non-REM sleep in depressed patients during
      treatment with trazodone.
AB  - Recently, it was hypothesized that acute or cumulative suppression of non-REM
      sleep intensity might be related to the therapeutic effects of antidepressants.
      This intensity has been proposed to be expressed in the EEG power density in non
      REM sleep. In the present study, the relationship was examined between the
      changes of EEG power density in non-REM sleep and the changes in clinical state
      in 8 depressed patients during treatment with trazodone. A 1-week wash-out period
      was followed by 1 week of placebo administration, a medication period of 5 weeks
      and a 1-week placebo period. To minimize systematic influences of sleep duration
      and non-REM-REM sleep alterations, EEG power was measured over the longest common
      amount of non-REM sleep stages 2-4 (168.5 min), accumulated from sleep onset
      onwards. During trazodone treatment, the 13- and 14-Hz bins showed a significant
      reduction in EEG power. No clear-cut change, however, was observed in the EEG
      power of the delta frequency range (1-4 Hz) which is considered to be the
      principle manifestation of non-REM sleep intensity. Furthermore, no overall
      significant relationship between EEG power suppression and clinical improvement
      could be demonstrated.

PMID- 8557884
TI  - Therapeutic efficacy of antidepressants in agitated anxious depression--a meta
      analysis of moclobemide studies.
AB  - The results of the meta-analysis of studies comparing the efficacy of
      moclobemide, imipramine and so-called sedative antidepressants (amitriptyline,
      mianserin and maprotiline) in 2416 patients are described. The results
      demonstrated that in agitated-anxious depressive patients (defined by HAMD factor
      score or HAMD item 9) a nonsedative, reversible MAO-A inhibitor moclobemide has
      about equal efficacy as imipramine or sedative antidepressants. All
      antidepressants were clearly superior to placebo, irrespective of the outcome
      measures applied (> 50% HAMD decrease, CGI improvement). The efficacy of
      antidepressants in agitated patients was unrelated to the severity of agitation
      and did not appear to be inferior to the efficacy in nonagitated patients.
      Comedication with benzodiazepines had no impact on overall efficacy of either
      moclobemide or other antidepressants in this patient population. Previous
      treatment with antidepressants, however, always negatively influenced the outcome
      with trial drugs, e.g., reduced their efficacy. Placebo response in agitated
      depressives appeared generally to be low (20-30%) and was clearly reduced with
      increased severity of agitation, irrespectively of how the agitation was defined.

PMID- 8557885
TI  - Anticipation in unipolar affective disorder.
AB  - Anticipation describes an inheritance pattern within a pedigree with an increase
      in disease severity and/or decrease in age at onset in successive generations.
      The phenomenon of anticipation has recently been shown to be correlated with the
      expansion of trinucleotide repeat sequences in a neuromuscular disease, various
      neurodegenerative disorders and mental retardation. We have studied parent
      offspring differences in age at onset and disease severity in 31 pairs with
      unilineal inheritance of unipolar affective disorder (UPAD). Life-table analyses
      showed a significant decrease in survival to 1st episode of major depression in
      the offspring generation compared with the parental generation (P = 0.0007).
      There was also a significant difference in age at onset (P < 0.001) between
      parents and offsprings. The offspring generation experienced onset 15.6 years
      earlier and illness 1.5 x more severe than did the parent generation.
      Furthermore, there was a significant correlation (P < 0.05) in age at onset
      between parent and offspring generations. When we excluded pairs where the
      affected parent has an age of onset greater than the age of the child at the time
      of ascertainment (i.e., 23 pairs left), there was still a significant (P = 0.02)
      decrease in age at onset (8.4 years) and 1.5 x more severe disease in the
      offspring generation. No evidence for specific maternal or paternal inheritance
      was found. We found evidence of anticipation in 75-80% of this sample of
      unilineal family pairs of UPAD. Anticipation is, thus, an inheritance pattern in
      a large group of UPAD which suggests that the expansion of trinucleotide repeat
      sequences is a possible mode of inheritance in this group of UPAD. The findings
      of anticipation in this study of families with UPAD and previous findings in
      families with BPAD suggest that the variable expression of unstable expansions of
      trinucleotide repeats may turn out to be the basis of the continuum of liability
      in affective disorders.

PMID- 8557886
TI  - Prevailing mood, mood changes and dreams in bipolar disorder.
AB  - In this preliminary and exploratory study, we collected the dream reports and
      mood ratings of 6 outpatients with bipolar disorder over a 6-month period to
      compare the relationship between dream themes and mood states. We found that
      neutral mood states were associated with mundane, routine or uneventful dreams
      while manic states featured bizarre and improbable dream themes. Neither
      depressed nor mixed states showed a consistent trend in dream themes. By
      categorizing the dreams that preceded mood shifts, we were able to identify a
      particular type of dream that seemed to precede a mood shift, particularly in the
      direction of mania. Shifts to mania were heralded by dreams of death and bodily
      injury. Forthcoming depression was more clearly associated with a decrease in
      overall number of dreams reported. The significance of dreaming in relation to
      mood is discussed in terms of these preliminary findings and our bipolar dream
      scale is offered for the convenience of subsequent investigators.

PMID- 8557887
TI  - The tridimensional personality questionnaire as a predictor of response to
      nefazodone treatment of depression.
AB  - Personality traits have emerged as the strongest identified predictors of
      response to antidepressant treatment of major depressive disorder (Peselow et
      al., 1992; Joyce et al., 1994). 18 subjects in the midst of a major depressive
      episode were treated with nefazodone in an open trial. All subjects completed
      Cloninger's tridimensional personality questionnaire (TPQ) before beginning
      treatment. A multiple regression analysis was performed in an attempt to
      replicate Joyce et al.'s (1994) finding that temperament type, as assessed by the
      TPQ, is a strong predictor of antidepressant response. A model involving TPQ
      reward dependence and harm avoidance scores, and their interaction, was found to
      significantly predict the response to nefazodone (r2 = 0.47, P < 0.027). When
      response was defined as a 50% decrease in HAM-D score at last visit, high reward
      dependence score alone significantly separated responders from nonresponders
      (Fisher's exact P = 0.050, df = 1). These results raise the intriguing
      possibility that TPQ scores may have direct clinical applications.

PMID- 8557888
TI  - The aetiology of depression in the carers of dementia sufferers.
AB  - OBJECTIVE: To examine the associations of depression in the carers of dementia
      sufferers, diagnosed on the basis of a semistructured interview. DESIGN: Case
      control study. SETTING: Referrals to clinical services. SUBJECTS: The informal
      carers of 109 dementia sufferers, 32 with depression and 77 without. MEASURES:
      Carers were interviewed using the Geriatric Mental State Schedule. The diagnosis
      of depression was made according to Research Diagnostic Criteria. Instruments
      used to assess associations included Carers' Stress Scale, Marital Intimacy
      Scale, Cornell Depression Scale and CAMCOG Schedule. RESULTS: Only increasing age
      was significantly associated with depression in the overall group of carers. The
      severity of cognitive impairment was significantly associated with depression in
      carers who lived with a dementia sufferer and a low level of premorbid marital
      intimacy was significantly associated with depression amongst carers who were
      marital partners. CONCLUSION: Few factors are clearly associated with depression
      in the carers of dementia sufferers. The pattern of associations was, however,
      different for carers in different situations.

PMID- 8557889
TI  - An examination of family functioning utilizing the circumplex model in
      psychiatrically hospitalized children with depression.
AB  - The purpose of the current study was to explore the relationship between
      childhood depression and family functioning. 11 children with depression and 11
      children without depression were compared via scores on the adaptability and
      cohesion dimensions of the FACES-III-K. Children with depression reported
      significantly less cohesive and more disengaged (displaying emotional
      separateness and lack of closeness) families than children without depression.
      Cohesion (the emotional bonding and individual autonomy of family members), but
      not adaptability, appears to be an important factor in the relationship between
      family functioning and childhood depression. Clinicians are advised to use
      treatments designed to help alleviate low family cohesion for children with
      depression.

PMID- 8557890
TI  - Clinical symptoms and platelet monoamine oxidase in subgroups and different
      states of affective disorders.
AB  - Platelet monoamine oxidase activity (MAO) and clinical symptoms were examined in
      116 individuals, 32 acute depressed patients and 84 healthy controls. The enzyme
      activity was lower in depressed women than controls. MAO activity correlated
      positively with rated clinical state in depressed women but not in depressed men.
      Patients were reexamined after 10 years and categorized into affective psychosis
      (endogenous) or neurotic depression (International Statistical Classification of
      Diseases, Injuries and Causes of Death, 1987; ICD-9). Neurotic depressed occurred
      frequently in the low activity group. Endogenously depressed showed positive
      correlation between MAO activity and rated clinical state. The association
      between platelet MAO activity and clinical state is discussed.

PMID- 8557891
TI  - Continued benefit of coronary stenting versus balloon angioplasty: one-year
      clinical follow-up of Benestent trial. Benestent Study Group.
AB  - OBJECTIVES: This study sought to determine the 1-year clinical follow-up of
      patients included in the Benestent trial. BACKGROUND: The Benestent trial is a
      randomized study comparing elective Palmaz-Schatz stent implantation with balloon
      angioplasty in patients with stable angina and a de novo coronary artery lesion.
      Seven-month follow-up data have shown a decreased rate of restenosis and fewer
      clinical events in the stent group. It is not established whether this favorable
      clinical outcome is maintained for longer periods or whether coronary stenting
      defers restenosis and its subsequent clinical manifestations. METHODS: To clarify
      this uncertainty, we updated clinical information on all but 1 of 516 patients
      enrolled in the Benestent trial (257 in balloon group, 259 in stent group) at
      least 12 months after the intervention. Major clinical events (primary clinical
      end point) were tabulated according to the intention to treat principle and
      included death, the occurrence of a cerebrovascular accident, myocardial
      infarction, the need for bypass surgery or a further percutaneous intervention in
      the previously treated lesion. RESULTS: After 1 year, no significant differences
      in mortality (1.2% vs. 0.8%), stroke (0.0% vs. 0.8%), myocardial infarction (5.0%
      vs. 4.2%) or coronary bypass graft surgery (6.9% vs. 5.1%) were found between the
      stent and balloon angioplasty groups, respectively. However, the requirement for
      a repeat angioplasty procedure was significantly lower in the stent group (10%)
      than the balloon angioplasty group (21%, relative risk [RR] 0.49, 95% confidence
      interval [CI] 0.31 to 0.75, p = 0.001), and overall primary end points were less
      frequently reached by stent group patients (23.2%) than those in the balloon
      group (31.5%, RR 0.74, 95% CI 0.55 to 0.98, p = 0.04). No differences were found
      between groups with respect to functional class angina and prescribed medication
      at the time of follow-up. CONCLUSIONS: These clinical follow-up data show that
      the benefit of elective native coronary artery stenting in patients with stable
      angina is maintained to at least 1 year after the procedure and results in a
      significantly reduced requirement for repeat intervention.

PMID- 8557892
TI  - Care of acute myocardial infarction by noninvasive and invasive cardiologists:
      procedure use, cost and outcome.
AB  - OBJECTIVES: This study sought to determine how noninvasive and invasive
      cardiologists may differ in the hospital care of patients with acute myocardial
      infarction. BACKGROUND: Scant information exists regarding the effect of
      noninvasive and invasive cardiology subspecialization on invasive cardiac
      procedural use, cost and outcome in the care of patients with acute myocardial
      infarction. METHODS: This study analyzed a prospective cohort of 292 patients
      admitted to an urban tertiary care hospital from the emergency room under the
      care of noninvasive or invasive cardiologists. Clinical characteristics; hospital
      course, including management, utilization of diagnostic coronary angiography and
      percutaneous transluminal coronary angioplasty; direct hospital costs; length of
      hospital stay; and post-hospital discharge follow-up data were collected by a
      prospective data base instrument. RESULTS: Despite similar clinical
      characteristics, extent and severity of coronary artery disease and utilization
      of diagnostic coronary angiography in the two groups of patients, those under the
      care of an invasive cardiologist were significantly more likely to undergo
      coronary angioplasty than those under the care of a noninvasive cardiologist. The
      direct hospital costs and length of stay of the noninvasive and invasive group
      patients who underwent coronary angioplasty were similar, although overall the
      direct hospital costs and length of stay were higher for the invasive than for
      the noninvasive group patients. CONCLUSIONS: Noninvasive and invasive
      cardiologists differ in their rate of utilization of coronary angioplasty in
      similar patients with acute myocardial infarction.

PMID- 8557893
TI  - Predictive power of increased heart rate versus depressed left ventricular
      ejection fraction and heart rate variability for risk stratification after
      myocardial infarction. Results of a two-year follow-up study.
AB  - OBJECTIVES: The aim of this study was to compare the predictive value of mean RR
      interval assessed from predischarge Holter recordings with that of heart rate
      variability and left ventricular ejection fraction for risk stratification after
      myocardial infarction. BACKGROUND: Heart rate variability is a powerful tool for
      risk stratification after myocardial infarction. Although heart rate variability
      is related to heart rate, little is known of the prognostic value of 24-h mean
      heart rate. METHODS: A total of 579 patients surviving the acute phase of
      myocardial infarction were followed up for at least 2 years. Predischarge heart
      rate variability, 24-h mean RR interval and left ventricular ejection fraction
      were analyzed. RESULTS: During the first 2 years of follow-up, there were 54
      deaths, 42 of which were cardiac (26 sudden). Shorter mean RR interval was a
      better predictor of all-cause mortality as well as cardiac and sudden death than
      depressed left ventricular ejection fraction. Depressed heart rate variability
      predicted the risk of death better than mean RR interval for sensitivities < 40%.
      For sensitivities > or = 40%, mean RR interval was as powerful as heart rate
      variability. All three variables performed equally well in predicting nonsudden
      cardiac death. For cardiac death prediction, a left ventricular ejection fraction
      < 35% had a 40% sensitivity, 78% specificity and 14% positive predictive
      accuracy; a mean RR interval < 700 ms had a 45% sensitivity, 85% specificity and
      20% positive predictive accuracy; and a heart rate variability < 17 U had a 40%
      sensitivity, 86% specificity and 20% positive predictive accuracy. CONCLUSIONS:
      Predischarge 24-h mean heart rate is a strong predictor of mortality after
      myocardial infarction that can compete with left ventricular ejection fraction
      and heart rate variability.

PMID- 8557894
TI  - Coronary risk factors measured in childhood and young adult life are associated
      with coronary artery calcification in young adults: the Muscatine Study.
AB  - OBJECTIVES: This study was designed to estimate the prevalence of coronary artery
      calcification in young adult men and women and to examine the association between
      the presence of coronary artery calcification and coronary risk factors measured
      in childhood and young adult life. BACKGROUND: Electron beam computed tomography
      is a sensitive, noninvasive method for detecting coronary artery calcification, a
      marker of the atherosclerotic process. Coronary artery calcification is
      associated with coronary risk factors in older adults. METHODS: Subjects (197
      men, 187 women) had coronary risk factors measured in childhood (mean age 15
      years) and twice during young adult life (mean ages 27 and 33 years). Each
      underwent an electron beam computed tomographic study at their second young adult
      examination. RESULTS: The prevalence of coronary artery calcification was 31% in
      men and 10% in women. Increased body size, increased blood pressure and decreased
      high density lipoprotein (HDL) cholesterol levels were the coronary risk factors
      that showed the strongest association with coronary artery calcification.
      Significant odds ratios for coronary artery calcification, using standardized
      risk factor measurements at a mean age of 33 years in men and women,
      respectively, were 6.4 and 13.6 for the highest decile of body mass index, 6.4
      and 6.4 for the highest decile of systolic blood pressure and 4.3 and 4.7 for the
      lowest decile of HDL cholesterol. CONCLUSIONS: Coronary artery calcification is
      more prevalent in men in this young adult population. Coronary risk factors
      measured in children and young adults are associated with the early development
      of coronary artery calcification. Increased body mass index measured during
      childhood and young adult life and increased blood pressure and decreased HDL
      cholesterol levels measured during young adult life are associated with the
      presence of coronary artery calcification in young adults.

PMID- 8557895
TI  - Prognostic value of coronary calcification and angiographic stenoses in patients
      undergoing coronary angiography.
AB  - OBJECTIVES: This investigation sought to determine the relative prognostic value
      of coronary calcific deposits and coronary angiographic findings for predicting
      coronary heart disease-related events in patients referred for angiography.
      BACKGROUND: The relation among coronary calcification, coronary stenoses and
      coronary heart disease-related events is of interest on a clinical as well as a
      pathophysiologic basis. METHODS: Four hundred ninety-one symptomatic patients
      underwent coronary angiography and electron beam computed tomography at five
      different centers between April 1989 and December 1993. The electron beam
      computed tomograms were interpreted by a cardiologist with no knowledge of the
      coronary angiographic and clinical data. Receiver operating characteristic (ROC)
      curves were constructed to determine the relation between electron beam computed
      tomographic and coronary angiographic findings. A follow-up telephone survey was
      completed in 86% of patients. The records for all patients who died or were
      admitted to the hospital for chest pain or suspected myocardial infarction were
      reviewed by three other cardiologists with no knowledge of the coronary
      angiographic and electron beam computed tomographic study results. RESULTS: The
      mean (+/- SE) area under the ROC curve was 0.75 +/- 0.02 for the coronary calcium
      score, indicating moderate discriminatory power for this score for predicting
      angiographic findings. Thirteen coronary heart disease-related deaths and eight
      nonfatal acute infarctions occurred over 30 +/- 13 months. Scores were sorted in
      ascending order and divided into quartiles of equal size. One patient in the
      first quartile had a fatal myocardial infarction (coronary calcium score range 0
      to 2.1); 2 in the second quartile (range 2.1 to 75.3), 8 in the third quartile
      (range 75.3 to 397.1) and 10 in the fourth quartile (> 397.1) had a coronary
      heart disease-related event. Application of bivariate logistic regression showed
      that log score but not number of angiographically diseased vessels significantly
      predicted the probability of a coronary heart disease-related event occurring
      during follow-up. CONCLUSIONS: Electron beam computed tomographic calcium scores
      correlate moderately well with angiographic findings. These scores predict
      coronary heart disease-related events in patients undergoing angiography as well
      as do the number of angiographically affected arteries.

PMID- 8557896
TI  - Functional behavior and morphology of the coronary artery wall in patients with
      Kawasaki disease assessed by intravascular ultrasound.
AB  - OBJECTIVES: To examine the development of coronary artery lesions in Kawasaki
      disease, we assessed the functional behavior and morphology of coronary arteries
      by intravascular ultrasound. BACKGROUND: Long-term follow-up studies of patients
      with Kawasaki disease have demonstrated the development of localized coronary
      stenoses even after aneurysms have regressed. It is also possible that
      angiographically normal coronary segments in patients with this disease may
      retain histologic changes. METHODS: Twenty-three patients followed up by serial
      coronary angiography were examined at a mean age +/- SD of 14.9 +/- 2.9 years.
      The thickness of the intima-media complex was measured by intravascular
      ultrasound (30 MHz; 3.5 or 4.3 F; 1,800 rpm). Coronary reactivity to
      nitroglycerin was determined by measuring percent changes in cross-sectional
      coronary artery area after intracoronary injection (7 microgram/kg body weight)
      of this agent. RESULTS: A remarkably thickened intima-media complex was observed
      at the sites with persisting (0.54 +/- 0.20 mm, n = 19) and regressed (0.84 +/-
      0.40 mm, n = 23) aneurysms. Mild thickening of the intima-media complex was often
      observed even in angiographically normal segments (0.22 +/- 0.05 mm, n = 31), in
      the left main coronary artery (0.47 +/- 0.15 mm, n = 20) and at normal branches
      (0.36 +/- 0.09 mm, n = 13). Coronary reactivity to nitroglycerin was
      significantly lower at the sites of regressed aneurysms (12.8 +/- 6.6%, n = 9)
      than in normal segments (32.8 +/- 10.9%, n = 13, p < 0.01), indicating the
      presence of functional impairment at the sites with regressed aneurysms.
      Decreased nitroglycerin reactivity was also observed in some segments without
      evidence of aneurysm. CONCLUSIONS: These results indicate that in patients with
      Kawasaki disease the coronary disease accompanying impaired reactivity to
      nitroglycerin is present at the sites of regressed aneurysms as well as in
      angiographically normal coronary segments. We suggest that these sites with
      morphologic and functional abnormalities are related to the development of
      significant stenosis.

PMID- 8557897
TI  - Dissociation of coronary vascular tolerance and neurohormonal adjustments during
      long-term nitroglycerin therapy in patients with stable coronary artery disease.
AB  - OBJECTIVES: We sought to examine whether long-term nitroglycerin treatment causes
      tolerance in large coronary arteries and whether the loss of vascular effects
      parallels neurohormonal adjustments. BACKGROUND: Nitroglycerin therapy is
      associated with increased plasma renin activity and aldosterone levels and a
      decrease in hematocrit. It is assumed that nitroglycerin tolerance results in
      part from these neurohormonal adjustments and intravascular volume expansion.
      METHODS: Three groups were studied: group I (n = 10), no prior nitroglycerin
      therapy; and group II (n = 10) and group III (n = 8), 24- and 72-h long-term
      nitroglycerin infusion (0.5 micrograms/kg body weight per min), respectively.
      Coronary artery dimensions were assessed using quantitative angiography. Plasma
      renin activity, plasma aldosterone and vasopressin levels and hematocrit were
      monitored before and during nitroglycerin infusions. RESULTS: In group I,
      increasing intravenous concentrations of nitroglycerin caused a dose-dependent
      increase of the midportion of the left anterior descending coronary artery
      (baseline diameter 2.13 +/- 0.07 mm [mean +/- SEM], maximally by 22 +/- 2%) and
      left circumflex coronary artery (baseline diameter 2.08 +/- 0.07) mm, maximally
      by 22 +/- 3%). An intracoronary nitroglycerin bolus (0.2 mg) caused no further
      significant increase in diameter, indicating maximal dilation. In group II (n =
      10), the baseline large coronary artery diameter under ongoing nitroglycerin was
      significantly larger than that in group I (left anterior descending artery 2.61
      +/- 0.08 mm, left circumflex artery 2.57 +/- 0.08 mm). Additional intravenous and
      intracoronary nitroglycerin challenges did not cause further dilation, indicating
      maximally dilated vessels. At the same time, plasma renin activity, plasma
      aldosterone and vasopressin levels were significantly increased, and hematocrit
      significantly decreased. In group III patients, the baseline diameter of the left
      anterior descending artery and the left circumflex artery did not differ from
      that in patients without nitroglycerin pretreatment, indicating a complete loss
      of nitroglycerin coronary vasodilative effects. These patients showed no
      significant increase in circulating neurohormonal levels but a significant
      decrease in hematocrit. CONCLUSIONS: Within 24 h of continuous nitroglycerin
      treatment, the coronary arteries were maximally dilated despite neurohormonal
      adjustments and signs of intravascular volume expansion. Within 3 days of
      nitroglycerin infusion, tolerance developed in the absence of neurohormonal
      activation. The dissociation of neurohormonal adjustments and tolerance in large
      coronary arteries indicates that after long-term nitroglycerin treatment, true
      vascular tolerance, perhaps from an intracellular tolerance step, may have
      developed.

PMID- 8557898
TI  - Flow-mediated vasodilation of human epicardial coronary arteries: effect of
      inhibition of nitric oxide synthesis.
AB  - OBJECTIVES: This study sought to investigate the role of nitric oxide, an
      endothelium-derived relaxing factor, in flow-mediated vasodilation in human
      epicardial coronary arteries. BACKGROUND: Endothelium-derived relaxing factors
      may be released from the coronary artery endothelium in response to increases in
      blood flow. METHODS: We studied the effect of the nitric oxide synthesis
      inhibitor NG-monomethyl-L-arginine (L-NMMA) on the flow-mediated vasodilation of
      epicardial coronary arteries in 12 patients, using quantitative angiographic and
      Doppler flow velocity measurements. Adenosine at 100 micrograms/min was infused
      into the left anterior descending coronary artery to test the dilator response of
      the proximal artery to increases in blood flow. Acetylcholine at 3 and 30
      micrograms/min was infused into the left coronary ostium to determine endothelium
      dependent vasodilation of the proximal left anterior descending artery. Adenosine
      and acetylcholine were infused before and after the intracoronary infusion of L
      NMMA (25 mumol/min for 5 min). RESULTS: Infusion of L-NMMA caused a significant
      decrease in the baseline diameter of the proximal left anterior descending artery
      (from 2.90 +/- 0.14 to 2.74 +/- 0.13 mm [mean +/- SEM], p < 0.01). Adenosine
      increased coronary blood flow before and after L-NMMA (+399.5 +/- 27.5% and
      +511.9 +/- 33.3%, respectively). Flow-mediated vasodilation was observed in the
      proximal left anterior descending artery before and after L-NMMA (+9.2 +/- 1.5%,
      p < 0.01 and +8.6 +/- 2.1%, p < 0.01, respectively). A dose of 3 micrograms/min
      of acetylcholine significantly dilated the proximal left anterior descending
      artery before L-NMMA (+7.6 +/- 1.0%, p < 0.01), but acetylcholine-induced
      vasodilation was attenuated after L-NMMA (-1.8 +/- 1.0%). CONCLUSIONS: Our data
      suggest that nitric oxide modulates basal coronary artery tone but that mediators
      other than nitric oxide may be responsible for the flow-mediated vasodilation of
      human epicardial coronary arteries.

PMID- 8557899
TI  - Combination therapy with metoprolol and nifedipine versus monotherapy in patients
      with stable angina pectoris. Results of the International Multicenter Angina
      Exercise (IMAGE) Study.
AB  - OBJECTIVES: This study was designed to investigate whether combination therapy
      with metoprolol and nifedipine provides a greater anti-ischemic effect than does
      monotherapy in individual patients with stable angina pectoris. BACKGROUND:
      Combination therapy with a beta-adrenergic blocking agent (which reduces
      myocardial oxygen consumption) and a dihydropyridine calcium antagonist (which
      increases coronary blood flow) is a logical approach to the treatment of stable
      angina pectoris. However, it is not clear whether, in individual patients, this
      combined therapy is more effective than monotherapy. METHODS: Two hundred eighty
      patients with stable angina pectoris were enrolled in a double-blind trial in 25
      European centers. Patients were randomized (week 0) to metoprolol (controlled
      release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) for 6
      weeks; placebo or the alternative drug was then added for a further 4 weeks.
      Exercise tests were performed at weeks 0, 6 and 10. RESULTS: At week 6, both
      metoprolol and nifedipine increased the mean exercise time to 1-mm ST segment
      depression in comparison with week 0 (both p < 0.01); metoprolol was more
      effective than nifedipine (p < 0.05). At week 10, the groups randomized to
      combination therapy had a further increase in time to 1-mm ST segment depression
      (p < 0.05 vs. placebo). Analysis of the results in individual patients revealed
      that 7 (11%) of 63 patients adding nifedipine to metoprolol and 17 (29%) of 59
      patients (p < 0.0001) adding metoprolol to nifedipine showed an increase in
      exercise tolerance that was greater than the 90th percentile of the distribution
      of the changes observed in the corresponding monotherapy + placebo groups.
      However, among these patients, an additive effect was observed only in 1 (14%) of
      the 7 patients treated with metoprolol + nifedipine and in 4 (24%) of the 17
      treated with nifedipine + metoprolol. CONCLUSIONS: The mean additive anti
      ischemic effect shown by combination therapy with metoprolol and nifedipine in
      patients with stable angina pectoris is not the result of an additive effect in
      individual patients. Rather, it may be attributed to the recruitment by the
      second drug of patients not responding to monotherapy.

PMID- 8557900
TI  - Effects of a new calcium antagonist, mibefradil (Ro 40-5967), on silent ischemia
      in patients with stable chronic angina pectoris: a multicenter placebo-controlled
      study. The Mibefradil International Study Group.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effects of mibefradil
      (Ro 40-5967) on the frequency and duration of episodes of asymptomatic ischemia
      in patients with stable angina pectoris and to determine the most efficient
      single therapeutic dose of this drug. BACKGROUND: Mibefradil is a novel calcium
      channel antagonist that shows a high bioavailability, induces no reflex
      tachycardia and has no negative inotropic effects. METHODS: In a multicenter,
      double-blind, placebo-controlled, parallel-design trial, 126 patients with
      chronic stable angina pectoris were studied. After 1 week of a placebo run-in
      period, patients were randomized to receive 25, 50, 100, 150 mg of mibefradil or
      placebo for 2 weeks. Ambulatory 48-h electrocardiographic (ECG) monitoring was
      performed at the end of both the placebo run-in period and the active treatment
      period. RESULTS: Compared with placebo, mibefradil was associated with
      significantly less ischemia as manifested during ambulatory ECG monitoring. In
      the 150- and 100-mg groups, respectively, the drug resulted in a 73% and 63%
      reduction in the frequency of episodes of ST segment depression and a 78% and 58%
      reduction in the total duration of ST segment depression. Highly significant
      linear dose-response relations were present across all treatment groups for
      ischemic episodes and ischemia duration (p < 0.001). Electrocardiographic
      abnormalities related to treatment were first-degree atrioventricular block,
      sinus bradycardia and short Wenckebach episodes, observed during sleep on Holter
      monitoring. All ECG events were dose related. CONCLUSIONS: Mibefradil is a new,
      safe, well tolerated and very effective dose-dependent anti-ischemic calcium
      channel antagonist.

PMID- 8557901
TI  - Dobutamine-induced hypoperfusion without transient wall motion abnormalities:
      less severe ischemia or less severe stress?
AB  - OBJECTIVES: This study sought to compare the clinical characteristics,
      hemodynamic response and severity of ischemia in patients with coronary artery
      disease and reversible perfusion defects on dobutamine 2-methoxy isobutyl
      isonitrile (MIBI) single-photon emission computed tomography (SPECT) with or
      without transient wall motion abnormalities. BACKGROUND: The occurrence of
      reversible perfusion defects without concomitant wall motion abnormalities in
      patients with coronary artery disease was attributed to less severe ischemia.
      However, little data are available to support this observation. METHODS: Fifty
      four consecutive patients with significant coronary artery disease and reversible
      perfusion defects on dobutamine (up to 40 micrograms/kg body weight per min) MIBI
      SPECT were studied (mean [+/- SD] age 59 +/- 11 years; 38 men, 16 women). All
      patients underwent simultaneous echocardiography. The myocardium was divided into
      six matched segments, and ischemic perfusion score was quantitatively derived in
      myocardial segments with reversible defects. RESULTS: New or worsening wall
      motion abnormalities occurred in 40 patients (74%) (group A) and were absent in
      14 (26%) (group B). There was no significant difference between the two groups
      with respect to age, previous myocardial infarction, number of abnormal coronary
      arteries (1.8 +/- 0.8 vs. 1.6 +/- 0.9), number of reversible perfusion defects
      (1.6 +/- 0.9 vs. 1.8 +/- 0.7) or ischemic perfusion score (412 +/- 750 vs. 526 +/
      553). Patients in group A had a higher prevalence of male gender (80% vs. 43%, p
      < 0.01), higher peak systolic blood pressure (147 +/- 30 vs. 127 +/- 31 mm Hg, p
      < 0.05), higher peak rate-pressure product (19,632 +/- 4,081 vs. 16,939 +/-
      4,344, p < 0.01) and a higher prevalence of angina (53% vs. 14%) and ST segment
      depression (55% vs. 14%) than group B (p < 0.05 for both). CONCLUSIONS: In
      patients with coronary artery disease and ischemia on dobutamine MIBI SPECT, the
      absence of transient wall motion abnormalities is associated with a similar
      extent and severity of reversible perfusion defects, a lower stress rate-pressure
      product and a higher prevalence of female gender than patients with transient
      wall motion abnormalities. Mechanically silent ischemia should not be regarded as
      a marker of less severe ischemia on myocardial perfusion scintigraphy.

PMID- 8557902
TI  - Analysis of interinstitutional observer agreement in interpretation of dobutamine
      stress echocardiograms.
AB  - OBJECTIVES: This study sought to determine the degree of interinstitutional
      agreement in the interpretation of dobutamine stress echocardiograms. BACKGROUND:
      Dobutamine stress echocardiography involves subjective interpretation. Consistent
      methods for acquisition and interpretation are of critical importance for
      obtaining high interobserver agreement and for facilitating communication of test
      results. METHODS: Five experienced centers were each asked to submit 30
      dobutamine stress echocardiograms (dobutamine up to 40 micrograms/kg body weight
      per min and atropine up to 1 mg) obtained in patients undergoing coronary
      angiography. Thus, a total of 150 dobutamine stress echocardiograms were
      interpreted by each center without knowledge of any other patient data. Left
      ventricular wall motion was assessed using a 16-segment model but was otherwise
      not standardized. No patient was excluded because of poor image quality or
      inadequate stress level. Echocardiographic image quality was assessed using a
      five-point scale. RESULTS: Angiographically significant coronary artery disease
      (> or = 50% diameter stenosis) was present in 95 patients (63%). By a majority
      decision (three or more centers), the sensitivity, specificity and accuracy of
      dobutamine echocardiography were 76%, 87% and 80%, respectively. Abnormal or
      normal results of stress echocardiography were agreed on by four or all five of
      the centers in 73% of patients (mean kappa value 0.37, fair agreement only).
      Agreement on the left anterior descending artery territory (78%) was similar to
      that for the combined right coronary artery/left circumflex artery territory
      (74%), and for specific segments the agreement ranged from 84% to 97% and was
      highest for the basal anterior segment and lowest for the basal inferior segment.
      Agreement was higher in patients with no (82%) or three-vessel coronary artery
      disease (100%) and lower in patients with one- or two-vessel disease (61% and
      68%, respectively). Agreement on positivity or negativity of stress test results
      was 100% for patients with the highest image quality but only 43% for those with
      the lowest image quality (p = 0.003). CONCLUSIONS: The current heterogeneity in
      data acquisition and assessment criteria among different centers results in low
      interinstitutional agreement in interpretation of stress echocardiograms.
      Agreement is higher in patients with no or advanced coronary artery disease and
      substantially lower in those with limited echocardiographic image quality. To
      increase interinstitutional agreement, better standardization of image
      acquisition and reading criteria of stress echocardiography is recommended.

PMID- 8557903
TI  - Six-month effects of early treatment with lisinopril and transdermal glyceryl
      trinitrate singly and together withdrawn six weeks after acute myocardial
      infarction: the GISSI-3 trial. Gruppo Italiano per lo Studio della Sopravvivenza
      nell'Infarto Miocardico.
AB  - OBJECTIVES: This 6-month follow-up analysis sought to assess whether the early
      reduction of mortality obtained with a 6-week treatment course of lisinopril or
      glyceryl trinitrate, or both, in unselected patients with acute myocardial
      infarction outlasts therapy and is still present after 6 months. The primary
      outcome of the 6-month follow-up was the combined end point of mortality and
      severe left ventricular dysfunction. BACKGROUND: The assumption was that the
      early benefit on remodeling processes may be maintained over a longer period of
      time, even in the absence of treatment. METHODS: A total of 19,394 patients with
      acute myocardial infarction were randomized within 24 h of onset of symptoms to a
      6-week treatment course of oral lisinopril or open control and, according to a 2
      x 2 factorial design, to glyceryl trinitrate or open control. Randomized
      treatments were stopped after 6 weeks in the absence of specific indications, and
      the patients were followed up for 6 months. RESULTS: At 6 months, among patients
      randomized to lisinopril, 18.1% died or developed severe ventricular dysfunction
      versus 19.3% of those randomized to no lisinopril (2p = 0.03). No difference was
      found between patients with and without glyceryl trinitrate therapy (18.4% vs.
      18.9%, 2p = 0.39). CONCLUSIONS: Although the systematic administration of
      glyceryl trinitrate started early and continued for 6 weeks after acute
      myocardial infarction does not yield evidence of benefit, early treatment with
      lisinopril appears to improve prognosis. This effect seems to carry over the
      first 6 months from randomization, even after treatment withdrawal.

PMID- 8557904
TI  - Prognostic value of cardiopulmonary exercise testing using percent achieved of
      predicted peak oxygen uptake for patients with ischemic and dilated
      cardiomyopathy.
AB  - OBJECTIVES: We tested the hypothesis that percent achieved of predicted peak
      oxygen uptake (predicted VO2max) improves the prognostic accuracy of identifying
      high risk ambulatory patients with congestive heart failure considered for heart
      transplantation compared with absolute peak oxygen uptake (VO2max) in 181
      patients with ischemic or dilated cardiomyopathy. BACKGROUND: Peak oxygen uptake
      during exercise has been shown to be a useful prognostic measurement to risk
      stratify patients with heart failure. The prognostic value of percent predicted
      VO2max has not been assessed in these patients. METHODS: We retrospectively
      studied 181 ambulatory patients referred to the Saint Louis University Heart
      Failure Unit. Clinical, hemodynamic (137 patients) and coronary angiographic (145
      patients) data were recorded, and all patients underwent symptom-limited
      cardiopulmonary exercise. RESULTS: During a mean follow-up period of 12 +/- 6
      months, 26 patients died, and 18 were listed as Status 1 priority for heart
      transplantation. The actuarial 1- and 2-year survival of the 89 patients who
      achieved < or = 50% predicted VO2max was 74% and 43%, respectively, compared with
      98% and 90% in the 92 who achieved > 50% predicted VO2max (p = 0.001).
      Multivariable analysis selected < or = 50% predicted VO2max as the most
      significant predictor of cardiac death (p = 0.007) and cardiac death or Status 1
      priority (p = 0.0005). CONCLUSIONS: Percent achieved of predicted VO2max provides
      important information that can be used to risk stratify ambulatory patients with
      heart failure with ischemic or dilated etiology that exceeds that provided by
      measurement of VO2max alone. Patients who achieve > 50% predicted VO2max have an
      excellent short-term prognosis when treated medically, and heart transplantation
      can be safely deferred.

PMID- 8557905
TI  - Hemodynamic effects of supplemental oxygen administration in congestive heart
      failure.
AB  - OBJECTIVES: This study sought to determine the hemodynamic effects of oxygen
      therapy in heart failure. BACKGROUND: High dose oxygen has detrimental
      hemodynamic effects in normal subjects, yet oxygen is a common therapy for heart
      failure. Whether oxygen alters hemodynamic variables in heart failure is unknown.
      METHODS: We studied 10 patients with New York Heart Association functional class
      III and IV congestive heart failure who inhaled room air and 100% oxygen for 20
      min. Variables measured included cardiac output, stroke volume, pulmonary
      capillary wedge pressure, systemic and pulmonary vascular resistance, mean
      arterial pressure and heart rate. Graded oxygen concentrations were also studied
      (room air, 24%, 40% and 100% oxygen, respectively; n = 7). In five separate
      patients, muscle sympathetic nerve activity and ventilation were measured during
      100% oxygen. RESULTS: The 100% oxygen reduced cardiac output (from 3.7 +/- 0.3 to
      3.1 +/- 0.4 liters/min [mean +/- SE], p < 0.01) and stroke volume (from 46 +/- 4
      to 38 +/- 5 ml/beat per min, p < 0.01) and increased pulmonary capillary wedge
      pressure (from 25 +/- 2 to 29 +/- 3 mm Hg, p < 0.05) and systemic vascular
      resistance (from 1,628 +/- 154 to 2,203 +/- 199 dynes.s/cm5, p < 0.01). Graded
      oxygen led to a progressive decline in cardiac output (one-way analysis of
      variance, p < 0.0001) and stroke volume (p < 0.017) and an increase in systemic
      vascular resistance (p < 0.005). The 100% oxygen did not alter sympathetic
      activity or ventilation. CONCLUSIONS: In heart failure, oxygen has a detrimental
      effect on cardiac output, stroke volume, pulmonary capillary wedge pressure and
      systemic vascular resistance. These changes are independent of sympathetic
      activity and ventilation.

PMID- 8557906
TI  - Enalaprilat augments arterial and cardiopulmonary baroreflex control of
      sympathetic nerve activity in patients with heart failure.
AB  - OBJECTIVES: This study sought to determine the effects of enalaprilat on reflex
      control of sympathetic nerve activity. BACKGROUND: Angiotensin-converting enzyme
      inhibitors decrease mortality in patients with congestive heart failure. Their
      efficacy appears to be related importantly to antiadrenergic effects, the
      mechanism for which has not been determined. Because baroreflexes tonically
      inhibit sympathetic outflow, and baroreflexes are blunted in heart failure, we
      hypothesized that these agents reduce sympathetic activity by augmenting
      baroreflexes. METHODS: We assessed baroreflex control of sympathetic nerve
      activity and heart rate in patients with congestive heart failure and in control
      subjects before and after enalaprilat (0.02 mg/kg body weight intravenously).
      Arterial baroreflexes were perturbed by bolus administration of sodium
      nitroprusside and phenylephrine. Cardiopulmonary baroreflexes were perturbed by
      lower body negative pressure and head-down tilt. Muscle sympathetic nerve
      activity was recorded by microneurography. RESULTS: Enalaprilat decreased
      systolic blood pressure in patients with heart failure and control subjects.
      Sympathetic nerve activity increased in control subjects but decreased in
      patients with heart failure after enalaprilat despite reductions in central
      venous pressure in this group. Baroreflex control of sympathetic nerve activity
      was unchanged by enalaprilat in control subjects. In patients with heart failure,
      both arterial and cardiopulmonary baroreflex control of sympathetic nerve
      activity was enhanced by enalaprilat. Baroreflex control of heart rate was
      unchanged by enalaprilat in either group. CONCLUSIONS: Enalaprilat augments both
      arterial and cardiopulmonary baroreflex control of sympathetic activity in heart
      failure. These augmented inhibitory influences are associated with a reduction in
      sympathetic outflow and may contribute to the beneficial effects of angiotensin
      converting enzyme inhibitors in heart failure.

PMID- 8557907
TI  - A new approach for evaluation of left ventricular diastolic function: spatial and
      temporal analysis of left ventricular filling flow propagation by color M-mode
      Doppler echocardiography.
AB  - OBJECTIVES: To evaluate left ventricular diastolic function and differentiate the
      pseudonormalized transmitral flow pattern from the normal pattern, the
      propagation of left ventricular early filling flow was assessed quantitatively
      using color M-mode Doppler echocardiography. BACKGROUND: Because the propagation
      of left ventricular early filling flow is disturbed in the left ventricle with
      impaired relaxation, quantification of such alterations should provide useful
      indexes for the evaluation of left ventricular diastolic function. METHODS: Study
      subjects were classified into three groups according to the ratio of early to
      late transmitral flow velocity (E/A ratio) and left ventricular ejection
      fraction: 29 subjects with an ejection fraction > or = 60% (control group); 34
      with an ejection fraction < 60% and E/A ratio < 1 (group I); and 25 with ejection
      fraction < 60% and E/A ratio > or = 1 (group II). The propagation of peak early
      filling flow was visualized by changing the first aliasing limit of the color
      Doppler signals. The rate of propagation of peak early filling flow velocity was
      defined as the distance/time ratio between two sampling points: the point of the
      maximal velocity around the mitral orifice and the point in the mid-left
      ventricle at which the velocity decreased to 70% of its initial value. High
      fidelity manometer-tipped measurement was performed in 40 randomly selected
      subjects. RESULTS: The rate of propagation decreased in groups I and II compared
      with that in the control group (33.8 +/- 13.8 [mean +/- SD] and 30.0 +/- 8.6 vs.
      74.3 +/- 17.4 cm/s, p < 0.001, respectively) and correlated inversely with the
      time constant of left ventricular isovolumetric relaxation and the minimal first
      derivative of left ventricular pressure (peak negative dP/dt) (r = 0.82 and r =
      0.72, respectively). CONCLUSIONS: Spatial and temporal analysis of filling flow
      propagation by color M-mode Doppler echocardiography was free of
      pseudonormalization and correlated well with the invasive variables of left
      ventricular relaxation.

PMID- 8557908
TI  - "Diastology": beyond E and A.

PMID- 8557909
TI  - Breakdown of blood pressure and body fluid homeostasis in heart transplant
      recipients.
AB  - OBJECTIVES: This study was designed to investigate disturbances in arterial blood
      pressure and body fluid homeostasis in stable heart transplant recipients.
      BACKGROUND: Hypertension and fluid retention frequently complicate heart
      transplantation. METHODS: Blood pressure, renal and endocrine responses to acute
      volume expansion were compared in 10 heart transplant recipients (57 +/- 9 years
      old [mean +/- SD]) 20 +/- 5 months after transplantation, 6 liver transplant
      recipients receiving similar doses of cyclosporine (cyclosporine control group)
      and 7 normal volunteers (normal control subjects). After 3 days of a constant
      diet containing 87 mEq/24 h of sodium, 0.154 mol/liter saline was infused at 8
      ml/kg per h for 4 h. Blood pressure and plasma vasopressin, angiotensin II,
      aldosterone, atrial natiuretic peptide and renin activity levels were determined
      before and at 30, 60, 120 and 240 min during the infusion. Urine was collected at
      2 and 4 h. Blood pressure, fluid balance hormones and renal function were
      monitored for 48 h after the infusion. RESULTS: Blood pressure did not change in
      the two control groups but increased in the heart transplant recipients (+15 +/-
      8/8 +/- 5 mm Hg) and remained elevated for 48 h (p < or = 0.05). Urine flow and
      urinary sodium excretion increased abruptly in the control groups sufficient to
      account for elimination of 86 +/- 9% of the sodium load by 48 h; the increases
      were blunted (p < or = 0.05) and delayed in the heart transplant recipients,
      resulting in elimination of only 51 +/- 13% of the sodium load. Saline infusion
      suppressed vasopressin, renin activity, angiotensin II and aldosterone in the two
      control groups (p < or = 0.05) but not in the heart transplant recipients. Heart
      transplant recipients had elevated atrial natriuretic peptide levels at baseline
      (p < or = 0.05), but relative increases during the infusion were similar to those
      in both control groups. CONCLUSIONS: Blood pressure in heart transplant
      recipients is salt sensitive. These patients have a blunted diuretic and
      natriuretic response to volume expansion that may be mediated by a failure to
      reflexly suppress fluid regulatory hormones. These defects in blood pressure and
      fluid homeostasis were not seen in liver transplant recipients receiving
      cyclosporine and therefore cannot be attributed to cyclosporine alone. Abnormal
      cardiorenal neuroendocrine reflexes, secondary to cardiac denervation, may
      contribute to salt-sensitive hypertension and fluid retention in heart transplant
      recipients.

PMID- 8557910
TI  - Immediate effects of lung transplantation on right ventricular morphology and
      function in patients with variable degrees of pulmonary hypertension.
AB  - OBJECTIVES: This study sought to determine the immediate effects of lung
      transplantation on right ventricular morphology and function in patients with
      variable degrees of pulmonary hypertension and to evaluate these features as
      potential markers of immediate outcome. BACKGROUND: Selected lung transplant
      recipients with severe preoperative pulmonary hypertension have previously been
      shown to have a reduction in right ventricular size and improved function at
      follow-up evaluation. METHODS: Thirty-two consecutive patients (mean [+/- SD] age
      44 +/- 11 years) were prospectively classified into three groups according to
      their pretransplantation pulmonary artery systolic pressure: severe pulmonary
      hypertensive group > or = 75 mm Hg, intermediate pulmonary hypertensive group 40
      to 74 mm Hg and non-pulmonary hypertensive group < 40 mm Hg. Hemodynamic and
      transesophageal echocardiographic variables were measured immediately before and
      after lung transplantation. RESULTS: Pulmonary artery systolic and mean pressures
      markedly decreased after transplantation in the severe pulmonary hypertensive
      group (from 115 +/- 26 to 45 +/- 19 mm Hg and from 76 +/- 14 to 31 +/- 11 mm Hg,
      respectively, both p < 0.05). Mean pulmonary artery pressure decreased in the
      intermediate group (from 34 +/- 7 to 26 +/- 7 mm Hg, p < 0.05). Right ventricular
      end-diastolic area, end-systolic area and eccentricity index decreased in the
      severe pulmonary hypertensive group after transplantation. End-diastolic area
      also decreased in the intermediate pulmonary hypertensive group. Right
      ventricular fractional area change was not significantly different between groups
      and did not change consistently after transplantation. Three patients with severe
      pulmonary hypertension who had continued depression of right ventricular function
      after transplantation died in the immediate postoperative period. CONCLUSIONS:
      Lung transplantation is associated with an immediate decrease in pulmonary artery
      pressures and right ventricular size and normalization of septal geometry but
      variable changes in right ventricular function. Continued depression of right
      ventricular fractional area change may be a potential marker of poor outcome.

PMID- 8557911
TI  - Determination of aortic valve area in valvular aortic stenosis by direct
      measurement using intracardiac echocardiography: a comparison with the Gorlin and
      continuity equations.
AB  - OBJECTIVES: This study sought to 1) show that intracardiac echocardiography can
      allow direct measurement of the aortic valve area, and 2) compare the directly
      measured aortic valve area from intracardiac echocardiography with the calculated
      aortic valve area from the Gorlin and continuity equations. BACKGROUND:
      Intracardiac echocardiography has been used in the descriptive evaluation of the
      aortic valve; however, direct measurement of the aortic valve area using this
      technique in a clinical setting has not been documented. Despite their
      theoretical and practical limitations, the Gorlin and continuity equations remain
      the current standard methods for determining the aortic valve orifice area.
      METHODS: Seventeen patients underwent intracardiac echocardiography for direct
      measurement of the aortic valve area, including four patients studied both before
      and after valvuloplasty, for a total of 21 studies. Immediately after
      intracardiac echocardiography, hemodynamic data were obtained from transthoracic
      echocardiography and cardiac catheterization. RESULTS: Adequate intracardiac
      echocardiographic images were obtained in 17 (81%) of 21 studies. The average
      aortic valve area (mean +/- SD) determined by intracardiac echocardiography for
      the 13 studies in the Gorlin analysis group was 0.59 +/- 0.18 cm2 (range 0.37 to
      1.01), and the average aortic valve area determined by the Gorlin equation was
      0.62 +/- 0.18 cm2 (range 0.31 to 0.88). The average aortic valve area determined
      by intracardiac echocardiography for the 17 studies in the continuity analysis
      group was 0.66 +/- 0.23 cm2 (range 0.37 to 1.01), and that for the continuity
      equation was 0.62 +/- 0.22 cm2 (range 0.34 to 1.06). There was a significant
      correlation between the aortic valve area determined by intracardiac
      echocardiography and the aortic valve area calculated by the Gorlin (r = 0.78, p
      = 0.002) and continuity equations (r = 0.82, p < 0.0001). CONCLUSIONS: In the
      clinical setting, intracardiac echocardiography can directly measure the aortic
      valve area with an accuracy similar to the invasive and noninvasive methods
      currently used. This study demonstrates a new, quantitative use for intracardiac
      echocardiographic imaging with many potential clinical applications.

PMID- 8557912
TI  - Mechanisms of hemolysis with mitral prosthetic regurgitation. Study using
      transesophageal echocardiography and fluid dynamic simulation.
AB  - OBJECTIVES: The aims of this study were to define the hydrodynamic mechanisms
      involved in the occurrence of hemolysis in prosthetic mitral valve regurgitation
      and to reproduce them in a numeric simulation model in order to estimate peak
      shear stress. BACKGROUND: Although in vitro studies have demonstrated that shear
      stresses > 3,000 dynes/cm2 are associated with significant erythrocyte
      destruction, it is not known whether these values can occur in vivo in conditions
      of abnormal prosthetic regurgitant flow. METHODS: We studied 27 patients
      undergoing reoperation for significant mitral prosthetic regurgitation, 16 with
      and 11 without hemolysis. We classified the origin and geometry of the
      regurgitant jets by using transesophageal echocardiography. By using the physical
      and morphologic characteristics defined, several hydrodynamic patterns were
      simulated numerically to determine shear rates. RESULTS: Eight (50%) of the 16
      patients with hemolysis had paravalvular leaks and the other 8 had a jet with
      central origin, in contrast to 2 (18%) and 9 (82%), respectively, of the 11
      patients without hemolysis (p = 0.12, power 0.38). Patients with hemolysis had
      patterns of flow fragmentation (n = 2), collision (n = 11) or rapid acceleration
      (n = 3), whereas those without hemolysis had either free jets (n = 7) or slow
      deceleration (n = 4) (p < 0.001, power 0.99). Numeric simulation demonstrated
      peak shear rates of 6,000, 4,500, 4,500, 925 and 950 dynes/cm2 in these five
      models, respectively. CONCLUSIONS: The distinct patterns of regurgitant flow seen
      in these patients with mitral prosthetic hemolysis were associated with rapid
      acceleration and deceleration or high peak shear rates, or both. The nature of
      the flow disturbance produced by the prosthetic regurgitant lesion and the
      resultant increase in shear stress are more important than the site of origin of
      the flow disturbance in producing clinical hemolysis.

PMID- 8557913
TI  - Functional results 5 years after successful percutaneous mitral commissurotomy in
      a series of 528 patients and analysis of predictive factors.
AB  - OBJECTIVES: This study sought to assess late functional results after successful
      percutaneous mitral commissurotomy and to determine their predictors. BACKGROUND:
      Few studies have reported late results of percutaneous mitral commissurotomy or
      have analyzed their late results regardless of immediate results, despite the
      fact that late deterioration may well be related either to a decrease in valve
      area or to poor initial results. METHODS: Between 1986 and 1992, 528 patients
      underwent successful percutaneous mitral commissurotomy (mean [+/- SD] age 46 +/-
      18 years; mean follow-up 32 +/- 18 months). A successful procedure was defined by
      a mitral valve area > or = 1.5 cm2 and no regurgitation > 2/4. Dilation was
      performed using a single balloon in 13 patients, a double balloon in 349 and the
      Inoue balloon in 166. Multivariate analysis was performed with a Cox model.
      RESULTS: The survival rate for patients in New York Heart Association functional
      class I or II, with no cardiac-related deaths or need for mitral surgery or
      repeat dilation, was 76 +/- 6% at 5 years. By multivariate analysis, the
      independent predictors of good functional results were echocardiographic group (p
      = 0.01), functional class (p = 0.02) and cardiothoracic index (p = 0.005) before
      the procedure and valve area after the procedure (p = 0.007). The predictive
      model derived allowed estimation of the probability of good functional results
      according to the value of these four predictors for any given patient.
      CONCLUSIONS: Good functional results were observed 5 years after successful
      percutaneous mitral commissurotomy in a large series of varied patients. The
      analysis of predictive factors may provide useful indications for follow-up
      results in patients undergoing this technique.

PMID- 8557914
TI  - Flow-mediated vasodilation during pacing of the free epigastric artery bypass
      graft early and late postoperatively.
AB  - OBJECTIVES: The free epigastric artery bypass graft is proposed as an alternative
      conduit to the saphenous vein graft, known for its high rate of attrition. The
      aim of our study was to assess its endothelial function in vivo. BACKGROUND: The
      endothelium of arterial bypass grafts plays a role in both the performance and
      the patency of such grafts. METHODS: We studied 73 epigastric grafts early (mean
      +/- SD 10 +/- 3 days) and 36 late (12 +/- 5 months) after coronary bypass surgery
      with quantitative angiography at rest, after 2 min of atrial pacing (130
      beats/min) and after injection of isosorbide dinitrate (1 to 2 mg) into the
      graft. RESULTS: At rest, mean epigastric graft diameter was lower in the late
      than in the early postoperative period (2.26 +/- 0.39 vs. 2.61 +/- 0.49 mm, p <
      0.001). Early after operation, epigastric grafts with a small or an intermediate
      runoff, but not those with a large runoff, were capable of vasodilation with
      nitrates (+0.09 +/- 0.10 mm). Late after operation, vasodilation after
      administration of isosorbide dinitrate was similar in epigastric grafts with a
      large runoff and in those with a small or intermediate runoff (+ 0.23 +/- 0.09
      vs. +0.23 +/- 0.18 mm). Significant vasodilation during pacing was observed late
      (+4 +/- 9%, p < 0.01) but not early postoperatively, except in a subset of
      patients with grafts capable of vasodilation after nitrates. A correlation
      between the response to nitrates and the response during pacing was observed
      early (r = 0.579, p < 0.001) and late postoperatively (r = 0.530, p = 0.02).
      CONCLUSIONS: Flow-mediated vasodilation during pacing was observed in most
      epigastric grafts late, but not early, after operation. This endothelium
      dependent dilation was correlated with the importance of the vasodilation
      observed with nitrates (endothelium-independent), which was related to the
      importance of the runoff only in the early postoperative period. The ability of
      epigastric grafts late postoperatively to dynamically adapt their dimensions to
      an acute increase in demand could contribute to the good functional results of
      this new alternative arterial graft.

PMID- 8557915
TI  - Effect of dual-chamber pacing on systolic and diastolic function in patients with
      hypertrophic cardiomyopathy. Acute Doppler echocardiographic and catheterization
      hemodynamic study.
AB  - OBJECTIVES: This study sought to evaluate prospectively the acute hemodynamic
      effect of dual-chamber pacing by using a combined hemodynamic approach of high
      fidelity pressure and Doppler velocity measurements. BACKGROUND: Dual-chamber
      pacing has been proposed recently as an alternative in the symptomatic treatment
      of patients with hypertrophic obstructive cardiomyopathy. Although early reports
      documented a decrease in left ventricular outflow tract gradient and symptomatic
      improvement, questions remain about the hemodynamic effects of dual-chamber
      pacing on systolic and diastolic function. METHODS: Twenty-nine patients with
      hypertrophic cardiomyopathy underwent a combined cardiac catheterization and
      Doppler echocardiographic study during normal sinus rhythm and P-synchronous
      pacing at various atrioventricular (AV) intervals. High fidelity pressure
      measurements of left ventricular inflow and left atrial pressures, ascending
      aortic pressure, thermodilution cardiac output and Doppler mitral flow velocity
      curves were obtained to evaluate both systolic and diastolic left ventricular
      function. RESULTS: During AV pacing at the shortest delay of 60 ms, there was a
      significant decrease in cardiac output (p < 0.05) and peak positive dP/dt (p <
      0.05), an increase in mean left atrial pressure (p < 0.05) and a prolongation of
      tau, the time constant of relaxation (p < 0.05), compared with that during normal
      sinus rhythm. During pacing at the optimal AV delay (longest AV interval with pre
      excitation), there was a similar trend, with deterioration in both systolic and
      diastolic function variables but of lesser magnitude than that during pacing at
      the shortest AV intervals. The deterioration in both systolic and diastolic
      function was present in 21 patients with and 8 without left ventricular outflow
      obstruction. There was a modest decrease in left ventricular outflow tract
      gradient from 73.3 +/- 45.0 (mean +/- SD) to 61.3 +/- 40.5 mm Hg (p = 0.03)
      during dual-chamber pacing at the optimal AV delay compared with that during
      normal sinus rhythm. CONCLUSIONS: The acute effect of pacing the right atrium and
      ventricle may be detrimental to both systolic and diastolic function of the left
      ventricle, particularly at the short AV intervals. Further studies of the long
      term effects of dual-chamber pacing in carefully performed randomized studies are
      needed.

PMID- 8557916
TI  - Appraisal of dual-chamber pacing therapy in hypertrophic cardiomyopathy: too soon
      for a rush to judgment?

PMID- 8557917
TI  - Classification of death in antiarrhythmia trials.
AB  - OBJECTIVES: We sought to develop and apply a new scheme for the classification of
      death to be used in trials of antiarrhythmia treatments. BACKGROUND: Because
      presently accepted classifications of death do not fully describe or tabulate all
      significant aspects of terminal events, nor do they consider unique aspects of
      arrhythmia investigations, a new classification scheme that addresses these
      issues is desirable. METHODS: A classification scheme of deaths that occur in
      antiarrhythmia trials was developed using the following categories: 1) primary
      organ cause (cardiac [arrhythmic, nonarrhythmic or unknown], noncardiac or
      unknown); 2) temporal course (sudden, nonsudden or unknown); 3) documentation
      (witnessed, monitored [yes, no or unknown]); 4) operative relation (preoperative,
      perioperative or postoperative); and 5) system relation (procedure related, pulse
      generator related and lead related [yes, no or unknown]). RESULTS: The
      classification scheme was used in a clinical trial of a new implantable
      cardioverter-defibrillator (1,250 patients, of whom 79 died) and used in an
      application for device market approval. Application of the classification to data
      reported using an older classification scheme is demonstrated. CONCLUSIONS: We
      propose a descriptive classification scheme that 1) fully describes and tabulates
      all significant aspects of terminal events; 2) incorporates previously used
      categorizations of death and new categorizations that address unique aspects of
      arrhythmia investigations; and 3) tabulates sufficient data to allow comparison
      with other studies. Events in a clinical trial of implantable defibrillator
      therapy were classified using the new classification scheme.

PMID- 8557919
TI  - Transthoracic defibrillation: importance of avoiding electrode placement directly
      on the female breast.
AB  - OBJECTIVES: This study sought to determine the effect on transthoracic impedance
      of placement of defibrillation electrodes on the female breast versus adjacent to
      or under the breast. BACKGROUND: Transthoracic impedance is a major determinant
      of transthoracic current flow in defibrillation. For a given energy setting, a
      high transthoracic impedance reduces current flow and may adversely affect the
      ability of electric shocks to accomplish defibrillation. We hypothesized that the
      increased interelectrode tissue associated with placement of the apex
      defibrillation electrode on the female breast would result in increased
      transthoracic impedance compared with electrode placement lateral to or under the
      breast. METHOD: Transthoracic impedance was measured noninvasively by passing a 5
      V, 31.25-kHz square wave current through the chest and comparing the low level
      current flow to known references. We measured transthoracic impedance associated
      with three different apex defibrillation electrode positions--on the breast,
      under the breast and lateral to the breast--in 25 women (brassiere size 34A to
      48C, 25 to 75 years old, body weight 128 to 328 lb [58 to 148 kg] and 2 men. The
      measurements were taken with a modified defibrillator that accurately predicts
      transthoracic impedance without delivering an actual shock. The measurement
      sequence was random. RESULTS: The average measured transthoracic impedance with
      placement of the apex defibrillation electrode on the breast was 95 +/- 25 ohms
      (mean +/- SD), under the breast 84 +/- 17* ohms and lateral to the breast 83 +/-
      20* ohms (asterisk indicates p < 0.01 vs. on the breast by analysis of variance).
      The study cohort was also classified into two groups: large breasted (brassiere
      size > or = 40) and small breasted (brassiere size < or = 39). The measured
      transthoracic impedances for the large-breasted group were 112 +/- 20 ohms for on
      the breast, 94 +/- 13* ohms for under the breast and 98 +/- 19* ohms for lateral
      to the breast. For the small breasted group, the similar transthoracic impedance
      measurements were 81 +/- 21, 77 +/- 16 and 71 +/- 13* ohms, respectively.
      CONCLUSIONS: In women, placement of the apex defibrillation electrode on the
      breast results in higher transthoracic impedance, which will reduce current flow.
      We recommend placing the apex electrode lateral to or underneath the breast.

PMID- 8557918
TI  - Familial cardiomyopathy underlies syndrome of right bundle branch block, ST
      segment elevation and sudden death.
AB  - OBJECTIVES: We sought to assess whether structural heart disease underlies the
      syndrome of right bundle branch block, persistent ST segment elevation and sudden
      death. BACKGROUND: Ventricular fibrillation and sudden death may occur in
      patients with a distinctive electrocardiographic (ECG) pattern of right bundle
      branch block and persistent ST segment elevation in the right precordial leads.
      METHODS: Sixteen members of a family affected by this syndrome underwent
      noninvasive cardiac evaluation, including electrocardiography, Holter ambulatory
      ECG monitoring, stress testing, echocardiography and signal-averaged
      electrocardiography; two patients had electrophysiologic and angiographic study.
      Endomyocardial biopsy was performed in one living patient, and postmortem
      examination, including study of the specialized conduction system, was performed
      in one victim of sudden death. RESULTS: Five years before a fatal cardiac arrest,
      the proband had been resuscitated from sudden cardiac arrest due to recorded
      ventricular fibrillation. Serial ECGs showed a prolonged PR interval, right
      bundle branch block, left-axis deviation and persistent ST segment elevation in
      the right precordial leads, in the absence of clinical heart disease. Postmortem
      investigation disclosed right ventricular dilation and myocardial atrophy with
      adipose replacement of the right ventricular free wall as well as sclerotic
      interruption of the right bundle branch. A variable degree of right bundle branch
      block and upsloping right precordial ST segment was observed in seven family
      members; four of the seven had structural right ventricular abnormalities on
      echocardiography and late potentials on signal-averaged electrocardiography. A
      sib of the proband also had a prolonged HV interval, inducible ventricular
      tachycardia and fibrofatty replacement on endomyocardial biopsy. CONCLUSIONS: An
      autosomal dominant familial cardiomyopathy, mainly involving the right ventricle
      and the conduction system, accounted for the ECG changes and the electrical
      instability of the syndrome.

PMID- 8557920
TI  - Pharmacologic alterations in human type I atrial flutter cycle length and
      monophasic action potential duration. Evidence of a fully excitable gap in the
      reentrant circuit.
AB  - OBJECTIVES: This study compared the effect of changes in action potential
      duration versus conduction velocity on atrial flutter cycle length to determine
      whether there is a fully or partially excitable gap in atrial flutter.
      BACKGROUND: In an excitable gap reentrant circuit, cycle length is proportional
      to conduction velocity. Action potential duration is not a direct determinant of
      cycle length when the gap is fully excitable. METHODS: Right atrial monophasic
      action potentials were recorded from 41 patients during type I atrial flutter
      before and during pharmacologic interventions. RESULTS: Adenosine (17 +/- 3 mg
      [mean +/- SD]) shortened (p < 0.001) action potential duration but did not change
      cycle length. Edrophonium (10 mg) had no significant effect on action potential
      duration or cycle length. Isoproterenol (0.03 microgram/kg body weight per min)
      shortened (p < 0.05) and procainamide (15 mg/kg, then 2 mg/min) prolonged (p <
      0.001) action potential duration and cycle length. Alterations in cycle length
      were not correlated with changes in action potential duration. Procainamide's
      prolongation of action potential duration was reversed by adenosine without
      affecting cycle length. Procainamide's prolongation of action potential duration
      and cycle length was partially reversed by isoproterenol. Adenosine's and
      isoproterenol's shortening of action potential duration and isoproterenol's
      shortening of cycle length were enhanced by procainamide. CONCLUSIONS: Atrial
      flutter cycle length is determined primarily by conduction velocity and does not
      depend directly on action potential duration. Atrial flutter has a fully
      excitable gap, and procainamide does not convert the gap from full to partial
      excitability. Adenosine and isoproterenol interact with procainamide such that
      their effects are enhanced and procainamide's effects are diminished.

PMID- 8557921
TI  - Five- to nine-year follow-up results of balloon angioplasty of native aortic
      coarctation in infants and children.
AB  - OBJECTIVES: To evaluate the usefulness of balloon angioplasty for relief of
      native aortic coarctation, we reviewed our experience with this procedure, with
      special emphasis on follow-up results. BACKGROUND: Controversy exists with regard
      to the role of balloon angioplasty in the treatment of native aortic coarctation.
      METHODS: During an 8.7-year period ending September 1993, 67 neonates, infants
      and children underwent balloon angioplasty for native aortic coarctation. A
      retrospective review of this experience with emphasis on long-term follow-up
      forms the basis of this study. RESULTS: Balloon angioplasty produced a reduction
      in the peak-to-peak coarctation gradient from 46 +/- 17 (mean +/- SD) to 11 +/- 9
      mm Hg (p < 0.001). No patient required immediate surgical intervention. At
      intermediate-term follow-up (14 +/- 11 months), catheterization (58 patients) and
      blood pressure (2 patients) data revealed a residual gradient of 16 +/- 15 mm Hg
      (p > 0.1). When individual results were scrutinized, 15 (25%) of 60 had
      recoarctation, defined as peak gradient > 20 mm Hg. Recoarctation was higher (p <
      0.01) in neonates (5 [83%] of 6) and infants (7 [39%] of 18) than in children (3
      [8%] of 36), respectively. Two infants in our early experience had surgical
      resection with excellent results. Three patients had no discrete narrowing but
      had normal arm blood pressure and had no intervention. The remaining 10 patients
      had repeat balloon angioplasty with reduction in peak gradient from 52 +/- 13 to
      9 +/= 8 mm Hg (p < 0.001). Reexamination 31 +/- 18 months after repeat
      angioplasty revealed a residual gradient of 3 to 19 mm Hg (mean 11 +/- 6). Three
      (5%) of 58 patients who underwent follow-up angiography developed an aneurysm.
      Detailed evaluation of the femoral artery performed in 51 (88%) of 58 patients at
      follow-up catheterization revealed patency of the femoral artery in 44 (86%) of
      51 patients. Femoral artery occlusion, complete in three (6%) and partial in four
      (8%), was observed, but all had excellent collateral flow. Blood pressure,
      echocardiography-Doppler ultrasound and repeat angiographic or magnetic resonance
      imaging data 5 to 9 years after angioplasty revealed no new aneurysms and minimal
      (2%) late recoarctation. CONCLUSIONS: On the basis of these data, it is concluded
      that balloon angioplasty is safe and effective in the treatment of native aortic
      coarctation; significant incidence of recoarctation is seen in neonates and
      infants; repeat balloon angioplasty for recoarctation is feasible and effective;
      and the time has come to consider balloon angioplasty as a therapeutic procedure
      of choice for the treatment of native aortic coarctation.

PMID- 8557922
TI  - The various therapeutic approaches to aortic coarctation: is it fair to compare?

PMID- 8557923
TI  - Morphologic and hemodynamic consequences after percutaneous balloon valvotomy for
      neonatal pulmonary stenosis: medium-term follow-up.
AB  - OBJECTIVES: This study sought to evaluate ventricular and valvular morphologic
      changes, hemodynamic consequences and clinical outcomes of pulmonary balloon
      valvotomy performed in the neonatal period. BACKGROUND: Previous studies support
      percutaneous balloon valvotomy as the management option of choice for infants and
      children with valvular pulmonary stenosis. Less information is available to
      define the impact of valvotomy on the clinical course when performed in the
      neonatal period. METHODS: Patient records, catheterization data, cineangiograms
      and selected echocardiograms (initial and most recent studies) of 37 consecutive
      neonates undergoing attempted balloon dilation were reviewed. RESULTS: Dilation
      was accomplished in 35 (94%) of 37 attempts. Immediately after dilation, the
      transvalvular peak to peak systolic gradient decreased from 60 +/- 22 mm Hg (mean
      +/- SD, range 20 to 100) to 11 +/- 10 mm Hg (range 0 to 45) (p < 0.0001), and the
      right ventricular/aortic systolic pressure ratio decreased from 1.25 +/- 0.43
      (range 0.5 to 2.6) to 0.66 +/- 0.22 (range 0.2 to 1) (p < 0.0001). Oxygen
      saturation measured by percutaneous oximetry increased from 80 +/- 7% to 92 +/-
      4% (p < 0.0001). Three patients died (8%), and two required repeat balloon
      dilation. At the follow-up visit (median 31 months, range 6 months to 8 years),
      the estimated peak instantaneous Doppler gradient was 15 +/- 9 mm Hg (range 6 to
      36). Thickening of valve leaflets, initially present in 93% of patients, was
      found in only 4%, and leaflet mobility improved in all. Hypoplasia of the right
      ventricle, initially present in 31%, was found in only 4% at the latest
      evaluation. Pulmonary annulus diameter Z score increased from -3 +/- 1.0 to 0 +/-
      0.1 (p < 0.0001). Freedom from reintervention was 90%, 84% and 84% at 1, 2 and 8
      years, respectively. CONCLUSIONS: These data support the application of balloon
      valvotomy as the initial intervention in the treatment algorithm for neonates
      with critical pulmonary valve stenosis. Medium-term follow-up observations
      demonstrate sustained hemodynamic relief and support maturation of the right
      ventricle and pulmonary valve annulus, with the expectation of a good long-term
      outcome.

PMID- 8557924
TI  - Balloon valvuloplasty in the neonate with critical pulmonary stenosis.

PMID- 8557925
TI  - Reversed shunting across the ductus arteriosus or atrial septum in utero heralds
      severe congenital heart disease.
AB  - OBJECTIVES: This study was performed to define the significance of Doppler color
      flow mapping in demonstrating reversal of the direction of the normal physiologic
      flow across the atrial septum and ductus arteriosus in the human fetus.
      BACKGROUND: Reversal of the physiologic shunting across the ductus arteriosus or
      atrial septum in utero (i.e., left to right) can be readily identified by Doppler
      color flow mapping, complemented by pulsed and continuous wave Doppler
      information. METHODS: We reviewed echocardiograms recorded at our three
      institutions from 1988 to 1993, which displayed reversal of flow by Doppler color
      flow in 53 fetuses of gestational age 18 weeks to term. The diagnoses were
      confirmed by postnatal echocardiography, operation or autopsy. Reversal of
      shunting was consistently associated with severe heart disease. RESULTS: Reversed
      atrial shunting was found with severe left heart obstructive lesions, including
      19 with hypoplastic left heart syndrome, 3 with critical aortic stenosis, 2 with
      double-outlet right ventricle and 1 each with an interrupted aortic arch,
      atrioventricular septal defect and severe left ventricular dysfunction due to
      dilated cardiomyopathy. Reversed ductus arteriosus shunting was found with severe
      right heart obstructive lesions, including nine fetuses with pulmonary atresia,
      six with severe obstructive tricuspid valve abnormalities, five with severe
      tetralogy of Fallot, four with Ebstein's anomaly and two with single ventricle
      and pulmonary stenosis. Associated cardiac lesions were common in both groups.
      Only 3 of the 15 infants who were delivered alive from the reverse ductus
      arteriosus shunt group and 4 of 12 from the reverse atrial shunt group still
      survive. CONCLUSIONS: The finding of reversed flow by Doppler color flow mapping
      during fetal life provides a key to subsequent accurate diagnosis and denotes a
      spectrum of diseases with a very poor prognosis.

PMID- 8557926
TI  - Long-term beta-blocker treatment prevents chronic creatine kinase and lactate
      dehydrogenase system changes in rat hearts after myocardial infarction.
AB  - OBJECTIVES: We tested the hypothesis that long-term beta-blocker treatment with
      bisoprolol prevents creatine kinase (CK) and lactate dehydrogenase system changes
      that occur after chronic myocardial infarction. BACKGROUND: The mechanism of the
      beneficial effect of beta-blocker therapy is still unclear. METHODS: Six groups
      of rats were studied. Sham operated (sham) and hearts with ligated left anterior
      descending coronary artery (myocardial infarction) were untreated, treated early
      (beginning 30 min after infarction) or treated late (beginning 14 days after
      infarction). After 8 weeks, hearts were isolated and buffer perfused
      isovolumetrically. With a left ventricular balloon, mechanical function was
      recorded at an end-diastolic pressure of 10 mm Hg. Biopsy samples of noninfarcted
      left ventricular tissue were taken. Enzyme activities were measured
      spectrophotometrically; isoenzymes were separated by agar gel electrophoresis;
      and total creatine levels were measured with high performance liquid
      chromatography. RESULTS: The decrease in left ventricular developed pressure in
      untreated hearts (120 +/- 9 vs. 104 +/- 5 mm Hg [mean +/- SE], p < 0.05, sham vs.
      myocardial infarction) after myocardial infarction was prevented by early
      treatment (118 +/- 9 vs. 113 +/- 4 mm Hg). Late treatment failed to improve
      mechanical function. Reduction of CK activity occurring in untreated infarcted
      hearts (6.4 +/- 0.3 vs. 5.1 +/- 0.3 IU/mg protein, p < 0.05, sham vs. myocardial
      infarction) was prevented by early beta-blocker therapy. The increase in CK
      isoenzyme BB and MB levels, decrease in mitochondrial CK isoenzyme levels and
      increase in anaerobic lactate dehydrogenase isoenzyme levels in untreated
      infarcted hearts did not occur during bisoprolol treatment. The decrease in total
      creatine levels after myocardial infarction (74.2 +/- 4.9 vs. 54.9 +/- 3.3
      nmol/mg protein, p < 0.05, sham vs. myocardial infarction) was prevented by
      bisoprolol treatment. Early treatment was more effective than late therapy in
      preventing CK and lactate dehydrogenase system changes. In addition, in sham
      hearts, a 40% increase of creatine levels above normal levels was detected.
      CONCLUSIONS: Bisoprolol prevented changes in CK and lactate dehydrogenase system
      that occur after myocardial infarction. These observations may be related to the
      beneficial effects of long-term beta-blocker treatment in patients with chronic
      myocardial infarction.

PMID- 8557927
TI  - Subacute stent thrombosis: evolving issues and current concepts.
AB  - During percutaneous coronary revascularization, intracoronary stents are
      effective in the treatment of abrupt vessel closure and improvement of suboptimal
      angioplasty results, and compared to balloon angioplasty, they reduce stenosis
      recurrence. Opposing these benefits, subacute thrombosis of stents is associated
      with a substantial increase in periprocedural morbidity and mortality. To review
      factors associated with stent thrombosis and to study the impact of evolving
      procedural techniques on the incidence of stent thrombosis, we reviewed all
      English articles from MEDLINE (1988 to 1995) with key words "stent" and
      "thrombosis." Stent registry data and recent abstracts from scientific meetings
      were also reviewed. Factors related to the clinical setting, the lesion, the
      stent and the procedural technique that affect the risk of stent thrombosis were
      identified. Sixty clinical studies were reviewed and include 7,914 patients
      receiving intracoronary stents. Studies were separated into those reporting
      stents placed emergently or electively without adjunct high-pressure balloon
      inflations, stents placed in saphenous vein graft conduits, and stents placed
      with high-pressure balloon inflations but without subsequent oral anticoagulants.
      Overall, subacute thrombosis was substantially higher in stents placed emergently
      (10.1%) compared to those placed electively (4.3%). Among contemporary trials
      employing high-pressure balloon inflations, the rate of stent thrombosis appears
      markedly lower (1.3%) despite reduced postprocedural anticoagulation. Taken
      together, these studies suggest factors associated with a heightened risk of
      stent thrombosis, many of which can be avoided with proper case selection and
      contemporary techniques.

PMID- 8557928
TI  - Current status of flow convergence for clinical applications: is it a leaning
      tower of "PISA"?
AB  - Spatial appreciation of flow velocities using Doppler color flow mapping has led
      to quantitative evaluation of the zone of flow convergence proximal to a
      regurgitant orifice. Based on the theory of conservation of mass, geometric
      analysis, assuming a series of hemispheric shells of increasing velocity as flow
      converges on the orifice--the so-called proximal isovelocity surface area (PISA)
      effect--has yielded methods promising noninvasive measurement of regurgitant flow
      rate. When combined with conventional Doppler ultrasound to measure orifice
      velocity, regurgitant orifice area, the major predictor of regurgitation
      severity, can also be estimated. The high temporal resolution of color M-mode can
      be used to evaluate dynamic changes in orifice area, as seen in many pathologic
      conditions, which enhances our appreciation of the pathophysiology of
      regurgitation. The PISA methodology is potentially applicable to any restrictive
      orifice and has gained some credibility in the quantitative evaluation of other
      valve pathology, particularly mitral and tricuspid regurgitation, and in
      congenital heart disease. Although the current limitations of PISA estimates of
      regurgitation have tempered its introduction as a valuable clinical tool,
      considerable efforts in in vitro and clinical research have improved our
      understanding of the problems and limitations of the PISA methodology and
      provided a firm platform for continuing research into the accurate quantitative
      assessment of valve regurgitation and the expanding clinical role of quantitative
      Doppler color flow mapping.

PMID- 8557929
TI  - A delayed answer to the calcium blocker question.

PMID- 8557930
TI  - Stress echocardiography for diagnosis of coronary artery disease.

PMID- 8557931
TI  - Antibiotic prophylaxis against infective endocarditis in mitral valve prolapse.

PMID- 8557932
TI  - ADA urges Congress to maintain nursing home standards.

PMID- 8557933
TI  - It's a war out there! Understanding 'tribal' affiliations in the workplace.
      Interview by Deborah Shattuck.

PMID- 8557934
TI  - How should nutrient databases be evaluated?

PMID- 8557935
TI  - How should nutrient databases be evaluated?

PMID- 8557936
TI  - Availability of foods in high schools: is there cause for concern?

PMID- 8557938
TI  - Development and validation of the Cholesterol-Saturated Fat Index (CSI)
      Scorecard: a dietary self-monitoring tool.
AB  - OBJECTIVE: The Cholesterol-Saturated Fat Index (CSI) Scorecard was developed and
      tested as a self-monitoring tool for patients consuming a cholesterol-lowering
      diet. SUBJECTS/DESIGN: Twelve nutritionists used the CSI Scorecard to estimate
      the CSI score of the same five food records. Subsequently, using a revised tool,
      12 subjects with hypercholesterolemia estimated the CSI score of their 4-day food
      records and 11 participated in evaluation meetings. STATISTICAL ANALYSES: Two
      tailed, one-sample t tests and the Spearman rho correlation test were used,
      respectively, to compare CSI Scorecard estimates of nutritionists and
      participants to CSI scores obtained from computer calculations. RESULTS: The CSI
      scores estimated by the nutritionists were close to the computed scores at the
      25th and 75th food record percentiles. The correlation of the estimated CSI
      scores of participants to the computed scores was rs = .8 (P < .05). APPLICATION:
      The CSI Scorecard is a new, simple, quick, and accurate dietary self-monitoring
      tool patients can use in research centers and primary care settings. By
      numerically illustrating the saturated fat and cholesterol content of foods, the
      CSI Scorecard facilitates dietary self-monitoring and, thus, self-efficacy in the
      adoption and maintenance of a cholesterol-lowering dietary pattern.

PMID- 8557937
TI  - Estimated effects of reducing dietary saturated fat intake on the incidence and
      costs of coronary heart disease in the United States.
AB  - OBJECTIVES: To estimate the effects of reducing dietary saturated fat intake on
      the incidence and economic costs of coronary heart disease (CHD) in the United
      States. DESIGN: Modeling techniques and data from secondary sources, including
      the Framingham Heart Study and the second and third National Health and Nutrition
      Examination Surveys, were used to estimate the effects on CHD incidence and
      associated costs of reducing dietary saturated fat intake as a percent of total
      energy by one to three percentage points. SUBJECTS: Persons aged 35 to 69 years
      who have total cholesterol levels of 5.17 mmol/L or higher and are currently free
      of CHD. RESULTS: Approximately 3 million first-time coronary events are estimated
      to occur over a 10-year period among persons with total cholesterol levels
      exceeding 5.17 mmol/L. Reducing saturated fat intake by one to three percentage
      points would reduce CHD incidence by 32,000 to 99,700 events and yield combined
      savings in medical expenditures and lost earnings ranging from $4.1 to $12.7
      billion over 10 years (estimates in 1993 US dollars). CONCLUSION: Population
      based interventions to encourage Americans to reduce dietary intake of saturated
      fat may prevent tens of thousands of cases of CHD and save billions of dollars in
      related costs.

PMID- 8557939
TI  - Picture-sort method for administering a food frequency questionnaire to older
      adults.
AB  - OBJECTIVE: To assess the validity of a picture-sort approach to administering the
      National Cancer Institute food frequency questionnaire to older adults. DESIGN: A
      picture-sort interview was conducted in each respondent's home. After the picture
      sort, a 24-hour recall interview was administered on the same occasion. Five
      additional in-home recall interviews were subsequently conducted at approximately
      1-month intervals. SUBJECTS/SETTING: Forty-seven female and 49 male volunteers
      aged 66 to 100 years were recruited from among Cardiovascular Health Study
      participants from Maryland and North Carolina. MAIN OUTCOME MEASURES: Estimates
      from the picture sort and the recall for intakes of macronutrients, cholesterol,
      fiber, and selected vitamins and minerals exclusive of supplements. STATISTICAL
      ANALYSES: Comparison of means estimated by the two methods and correlation
      analyses were used. Correlations were adjusted under varied assumptions about the
      nature of the information contained in the six 24-hour recalls relative to
      respondents' usual intakes. RESULTS: After correction for attenuation, Pearson
      correlation coefficients for macronutrients ranged from .41 for protein to .74
      for saturated fat and cholesterol. For vitamins and minerals, correlations ranged
      from .26 for beta carotene to .62 for calcium. APPLICATIONS: Picture-sort
      estimates of mean nutrient intakes were comparable with estimates based on 24
      hour recalls, and correlations with reference data were similar to those reported
      in the literature for conventionally administered food frequency questionnaires.
      This dietary assessment method may, therefore, offer a way to simplify or
      structure responses to improve ease of administration and increase respondents'
      liking for the interview without loss of data quality.

PMID- 8557940
TI  - Athetosis increases resting metabolic rate in adults with cerebral palsy.
AB  - OBJECTIVES: To determine whether resting metabolic rate (RMR) is higher or lower
      in adults with cerebral palsy compared with the RMR of control subjects and to
      further examine physical characteristics of cerebral palsy that might affect RMR.
      DESIGN: Twenty-one adults with cerebral palsy (9 women, 12 men) were compared
      with 50 control subjects (25 men, 25 women) within the same age range (18 through
      50 years). The following measurements were made: RMR by indirect calorimetry,
      anthropometrics, body composition, and habitual physical activity patterns. The
      study was conducted at the University of Vermont General Clinical Research Center
      and the Ball State University Human Performance Laboratory. STATISTICAL ANALYSES:
      Mean values +/- standard deviations, t tests, Pearson product-moment correlation
      coefficients, analysis of covariance, and stepwise multiple correlation
      regression analysis were used to examine the relationships among variables of
      interest. RESULTS: No significant differences were found in body weight, body
      mass index, fat mass, percentage body fat, and measured RMR between the two
      groups. The subjects with cerebral palsy were significantly shorter, had less fat
      free mass, and expended fewer kilocalories in leisure time activities than the
      control subjects. After statistical adjustment for differences in fat-free mass,
      the subjects with cerebral palsy had a 14% (P < .001) higher adjusted RMR (1,742
      kcal/day) compared with that of the control subjects (1,534 kcal/day). According
      to stepwise regression analysis, RMR was best predicted in the entire sample by
      fat-free mass and the presence or absence of athetosis (multiple R = .83, P <
      .001). The presence of cerebral palsy alone was not significantly correlated with
      RMR. CONCLUSIONS: The increased energy requirements of adults with cerebral palsy
      can be partially explained by athetotic movements. In this sample, the presence
      of athetosis increased RMR by an average of 524 kcal/day.

PMID- 8557941
TI  - Food sources and dietary intakes of vitamin K-1 (phylloquinone) in the American
      diet: data from the FDA Total Diet Study.
AB  - OBJECTIVE: To identify important food sources and estimate dietary intake of
      vitamin K-1 (phylloquinone) in the American diet. DESIGN: Core foods from the US
      Food and Drug Administration (FDA) Total Diet Study (TDS), which was based on the
      1987-88 Nationwide Food Consumption Survey (NFCS), were analyzed for vitamin K-1.
      These nutrient values were then applied to the FDA TDS consumption model.
      SUBJECTS: Of the NFCS participants within the 14 selected age-gender groups,
      3,634 who had 3 days of dietary data were included in the FDA TDS consumption
      model. MAIN OUTCOME MEASURES: Vitamin K-1 intakes were estimated for each of the
      age-gender groups; the percentage contribution of each food item to total intake
      of vitamin K-1 was calculated from the FDA TDS model. RESULTS: Of the 14 age
      gender groups selected, the 25- to 30-year-old women and men consumed less than
      the current Recommended Dietary Allowance (RDA) for vitamin K. In contrast,
      formula-fed infants had estimated vitamin K-1 intakes six times greater than the
      RDA. All other groups consumed amounts within the recommended daily intakes but
      lower than 90 micrograms/day. The top contributors to total vitamin K-1 intake
      were dark-green vegetables, although the fats and oils added to mixed dishes and
      desserts were also important contributors. The proportion of vitamin K-1 obtained
      from vegetables increased with age. APPLICATIONS: The data identify important
      dietary sources of vitamin K-1 in the American diet. This knowledge can be used
      to develop dietary assessment instruments for use in epidemiologic studies.

PMID- 8557942
TI  - Dietary nutrient profiles of Canadian Baffin Island Inuit differ by food source,
      season, and age.
AB  - OBJECTIVE: To compare the effect of food source (traditional or market), season
      (six seasons), and age (five age groups) on dietary nutrient patterns of Inuit
      living in Baffin Island, Canada. DESIGN: Twenty-four-hour recall interviews of
      all residents who had lived > or = 3 years in this one community in each of six
      seasons. Foods that were recalled were divided by source. SETTING/SUBJECTS: The
      study took place in the Inuit community of Qikiqtarjuaq, which harvests the
      highest quantity of wildlife per capita of all Baffin communities. Three hundred
      sixty-six residents contributed a total of 1,410 recalls: 401 from nonpregnant,
      nonlactating adult women, 74 from pregnant women, 301 from adult men, 451 from
      children aged 3 to 12 years, and 183 from teenagers aged 13 to 19 years.
      Participation was voluntary and averaged 65% to 75% of residents. MAIN OUTCOME
      MEASURES: Energy, total dry weight of food, and dietary nutrients (ie,
      carbohydrate, protein, total fat, saturated fat, polyunsaturated fat, vitamin A,
      iron, copper, zinc, calcium, phosphorus, magnesium, and sodium) were measured by
      food source, season, and age. Nutrient density (nutrient per 1,000 kcal) was
      calculated in traditional and market food sources. Selected nutrients were
      computed in total diets, and compared with Recommended Dietary Allowances (RDAs).
      STATISTICAL ANALYSES PERFORMED: Tests for normality of the distribution of
      nutrient intakes (ie, Shapiro-Wilk statistic) were performed followed by
      nonparametric analyses (ie, Wilcoxon paired-sample t test, Kruskal-Wallis
      analysis of variance, and adjustment for Bonferroni inequalities resulting from
      multiple comparisons). RESULTS: Most nutrient intakes were significantly
      different by food source (P < .05). Traditional food contributed more protein,
      phosphorus, iron, zinc, copper, magnesium, and vitamin A for several age groups.
      Market food contributed greater amounts of dry weight, energy, fat, carbohydrate,
      calcium, and sodium for most age groups. Seasonal variation (P < .05) existed for
      nutrients coming from traditional and market food. Of the 10 nutrients assessed
      for nutrient density, all except calcium and sodium were present in greater
      amounts in traditional food than in market food (P < .05). Calcium and vitamin A
      intakes fell below 66.6% of the RDAs for more than 60% of the population.
      CONCLUSIONS: The comprehensive view of nutrient profiles, food source, and
      seasonality of Inuit diets will assist health professionals in developing
      nutrition promotion and education programs for all age groups of this population.
      Traditional food is an essential source of the total annual dietary nutrient
      intake of Inuit. Results indicated, however, that calcium and vitamin A intake
      must be improved.

PMID- 8557943
TI  - Food safety: review and implications for dietitians and dietetic technicians.
AB  - Section 103 (d) of the Americans with Disabilities Act directs the secretary of
      health and human services to identify, publish, and annually review a list of
      pathogens transmitted via food contaminated by infected food handlers. The
      secretary is also directed to publish means by which diseases on the list are
      transmitted. The intent of the list is to protect disabled food handlers when
      they become ill and to provide managers with information for determining when to
      remove or reassign disabled food handlers who have infectious or communicable
      diseases to jobs that do not involve handling food. Pathogens often transmitted
      via food contaminated by infected food handlers are Salmonella typhi, Shigella
      species, Staphylococcus aureus, Streptococcus pyogenes, hepatitis A virus, and
      the Norwalk and Norwalk-like viruses. This article discusses section 103 (d) and
      for each of the six pathogens describes characteristics and growth requirements,
      types of foods involved in outbreaks, factors that contribute to foodborne
      outbreaks, and prevention and control measures. Human beings are the only
      reservoir of Sal typhi. The source of Shigella species is the intestinal tract of
      human beings and other primates. Human beings are the common reservoir of Staph
      aureus and Strep pyogenes. Staph aureus is frequently found in the nose and on
      the skin of healthy people, whereas Strep pyogenes is carried in the throat of
      infected or asymptomatic carriers. Foodborne viruses of public health concern
      originate in the human intestine. Foods that favor the multiplication of Sal
      typhi are often foods that require no cooking. Many outbreaks of foodborne
      disease attributed to Shigella species and viruses have been associated with
      salads. Moist, high-protein, and salty foods that have been cooked are most often
      involved in outbreaks of staphylococcal foodborne illness. Foods usually
      implicated in Strep pyogenes outbreaks are predominately composed of milk, eggs,
      or meat. Dietitians and dietetic technicians can use three approaches to reduce
      the incidence of foodborne disease attributed to food handlers: conducting
      training and education programs, implementing a Hazard Analysis and Critical
      Control Points system, and supporting certification of foodservice managers.

PMID- 8557944
TI  - Managing osteopetrosis in children: a nutrition challenge.
AB  - Osteopetrosis, a rare condition caused by a failure of osteoclasts to resorb
      bone, results in dense and deformed bones, growth failure, anemia, hypoplastic
      dentition, chronic infection, blindness, and massive splenomegaly. Children with
      infantile osteopetrosis have disease-related complications that affect
      nutritional status. Altered calcium and phosphorus intake has been reported in
      these patients, but previous studies did not include an assessment of dietary
      adequacy or nutrition-related complications. A prospective study of six children
      with severe infantile osteopetrosis was conducted to identify specific nutrition
      related problems and effective nutrition intervention strategies. Patients were
      monitored by a registered dietitian while they participated in a clinical
      research protocol at St Jude Children's Research Hospital. Dietary records for
      each patient were obtained at set intervals during the 4-month study period.
      Because most patients lacked adequate dentition, they had difficulty obtaining
      adequate nutrition through normal oral intake. Three children required nutrition
      supplementation (enteral feedings for one and oral supplements for two). We
      conclude that oral and enteral nutrition support can provide nutrients needed for
      improved growth and response to treatment in patients with osteopetrosis.

PMID- 8557945
TI  - An interdisciplinary nutrition support team improves quality of care in a
      teaching hospital.

PMID- 8557946
TI  - Maternal weight gains in ideal twin outcomes.

PMID- 8557947
TI  - Sex-role orientation and career importance factors do not explain salary
      inequities between male and female foodservice directors.

PMID- 8557948
TI  - Position of the American Dietetic Association: oral health and nutrition.

PMID- 8557949
TI  - Optometry: an international discipline.

PMID- 8557950
TI  - Optometry at the University of Melbourne in Australia.

PMID- 8557951
TI  - The refractive index and protein distribution in the blue eye trevally lens.
AB  - BACKGROUND: The relationship between structure (crystallin distribution) and
      function (refractive index) in the lens is not understood and can be studied by
      comparing biochemical and optical properties. Such a comparison has been made
      using a blue eyed trevally lens. METHODS: The optical parameter of refractive
      index distribution was determined using a nondestructive ray tracing technique.
      The distributions of the various classes of proteins in the lens were determined
      by dissolving lenses in concentric layers and using biochemical protein assay.
      HPLC and SDS-PAGE electrophoresis were used to investigate the proportion of
      proteins in each layer. RESULTS: The refractive index distribution, from center
      to edge, follows a second order polynomial. The proteins do not vary in their
      proportions over most of the lens; only in the inner-most regions is there a
      rapid increase in insoluble protein and a concomitant decrease in the soluble
      protein classes. The smallest proteins (gamma crystallins) become insoluble later
      than the alpha- and beta-crystallins. CONCLUSIONS: There are no similarities in
      the distributions of any of the protein classes to that of the refractive index
      in the fish lens. This result indicates that a quantitative relationship cannot
      be derived by comparing protein to refractive index distributions. However, the
      findings are consistent with those made in other species: a high content of gamma
      crystallins is always found in lenses which have steep refractive index gradients
      and high index magnitudes.

PMID- 8557952
TI  - The effectiveness of putative anti-cataract agents in the prevention of protein
      glycation.
AB  - BACKGROUND: Recent data have favored non-enzymatic glycation as a likely
      mechanism in diabetic cataract formation. The advanced glycation end products
      (AGEs) that are formed lead to opacification of the lens by disrupting the short
      range order between the proteins. Attempts to decrease AGE formation has led to
      the use of various anti-glycating agents. Their efficacy, however, has been
      questionable. METHODS: The extent of AGE formation was monitored in fetal bovine
      eyes using non-tryptophan fluorescence. The amount of carbohydrate bound to the
      proteins was measured after reduction with radio-labelled sodium borohydride.
      RESULTS: While the addition of glucose, glucose-6-phosphate or fructose increased
      the levels of glycation by only 25 percent and the levels of AGEs by 40 percent,
      glyceraldehyde resulted in a 70 percent increase in glycation and showed
      extensive AGE formation (an increase of over 6600 percent when compared to the
      unglycated protein). The anti-glycating agents aspirin and ibuprofen were unable
      to significantly decrease the extent of bound metabolite or reduce the amount of
      AGE formed. In contrast, penicillamine and aminoguanidine were more effective in
      reducing the levels of AGEs, even though the levels of bound metabolite appeared
      unchanged. CONCLUSIONS: Triose phosphates are likely to be the major metabolic
      intermediates that result in AGE formation. The anti-glycating agents, whereas
      penicillamine and aminoguanidine-which react with the Amadori-derived
      fragmentation products-significantly decreased levels of AGEs.

PMID- 8557953
TI  - Amino acids in neurotransmission and disease.
AB  - BACKGROUND: The amino acids, glutamate, GABA and glycine are involved in normal
      cellular function as well as in neuro-transmission. Glutamate in particular may
      be linked to neuron development and an oversupply may be the major cause of many
      acute and chronic neurological diseases. Such diseases include retinopathy of
      prematurity, glaucoma, hypertension, diabetes and ischemic damage secondary to
      vessel occlusion. CONCLUSIONS: This paper provides a review of the localization,
      proposed function and the mechanisms of manufacture and deactivation of the amino
      acid neurotransmitters. Current mechanisms of excitotoxicity are also discussed.
      In addition, the data presented from an animal model of retinal ischemia show
      morphological and neurochemical changes consistent with glutamate induced
      neurotoxicity.

PMID- 8557954
TI  - Clinical evaluation of refractive techniques.
AB  - BACKGROUND: The accuracy of two commercially available auto kerato-refractometers
      (Shin-Nippon Automatic Ref-Keratometer model RC380 and Topcon Auto Kerato
      Refractometer model KR-3100) and one autokeratometer (Alcon Systems Auto
      Keratometer) was compared to that of subjective refraction and conventional
      keratometry. METHODS: Refractive error and corneal curvature were measured on 20
      subjects. Measurements were converted from the standard clinical format of
      sphere, cylinder and axis to a vector format to assess the contribution of
      spherical and cylindrical errors simultaneously. RESULTS: For measurements of
      refractive error taken in immediate succession, the Shin-Nippon instrument was
      found to be more repeatable than the Topcon instrument. This trend reversed when
      subjects were realigned between measurements. The 95 percent confidence limit for
      precision for subjective refraction was considerably greater: 93 percent of
      subjective refractions resulted in visual acuities better than or equal to 6/6,
      compared with 85 percent for the Topcon instrument and 45 percent for the Shin
      Nippon instrument. Each of the methods for measuring corneal curvature showed
      minimal bias and comparable precision. CONCLUSIONS: Although subjective methods
      of determining refractive error generally achieved the same or better visual
      acuity as the automated methods, they displayed considerably poorer precision.
      Each of the methods of measurement of corneal curvature produced similar results.

PMID- 8557955
TI  - Using computers to test visual acuity.
AB  - BACKGROUND: This paper describes a computer-generated acuity test that can be
      produced on IBM compatible equipment in the Windows 3.1 environment. METHODS: The
      acuity test was applied to 14 observers using two psychophysical methods
      (staircase and method of constant stimuli [MOCS]) to determine the validity and
      reliability of the outcomes. Comparisons were made between test methods and a
      hard copy LogMAR chart using statistics suited to intra-class comparisons. The
      effect that screen luminance has on outcomes and hardware warm-up requirements
      were also considered. RESULTS: The computer staircase was found to provide a
      reliable estimate of acuity. The hard copy chart and computer staircase have an
      Intraclass Correlation Coefficient (ICC) of 0.98. The threshold derived from the
      different psychophysical methods is also highly correlated (ICC = 0.98). The
      monitor provides a stable luminance 30 minutes after a cold start, and a 1
      logunit (10 times) change in screen luminance has little effect on outcomes.
      CONCLUSIONS: A computer-driven acuity staircase provides a good estimate of
      threshold if a 30-minute warm-up period is allowed to stabilize monitor
      luminance. It also gives a measure of variability. A staircase is adequate for
      clinical applications as it provides a reasonable compromise between test time
      and accuracy. An extra 30 seconds is needed to obtain a staircase result
      (compared with hard copy), which is offset by the provision of this error term.

PMID- 8557956
TI  - The effects of short-term contact lens wear on adherence of Pseudomonas
      aeruginosa to human corneal cells.
AB  - BACKGROUND: Ulcerative keratitis is the most serious complication of contact lens
      wear, with the majority of infections being attributed to Pseudomonas aeruginosa.
      The degree to which bacteria adhere to the cornea may indicate its susceptibility
      to infection. It has been found that long-term contact lens wear leads to
      increased adherence of Pseudomonas aeruginosa to corneal epithelial cells. This
      study examines the effect of short-term contact lens wear. MEANS: Cells were
      collected using a non-contact corneal irrigation system from a total of 16
      subjects fitted with tight and loosely-fitted soft contact lenses. The control
      group consisted of 10 subjects with no recent contact-lens-wearing experience,
      eight of whom were later fitted with lenses to form a neophyte group. Six contact
      lens wearers formed the experienced group. After wearing lenses for a 30-hour
      period, including overnight, the collected corneal cells were incubated with
      Pseudomonas aeruginosa, differentially stained with Acridine orange and examined
      under fluorescence microscopy. RESULTS: The number of bacteria adhering to the
      cells was determined for the control group, neophyte and experienced groups. The
      frequency distribution profiles were similar for all groups and did not vary
      significantly between lens-wearing and non-wearing conditions, between neophyte
      and experienced wearers, or with lens fit. CONCLUSIONS: Using the technique
      reported, short-term extended contact lens wear produced minimal detectable
      changes in the potential of corneal epithelium cells to bind bacteria.

PMID- 8557957
TI  - Bibliography of the current world literature in hypertension.

PMID- 8557958
TI  - Vascular structure in NG-nitro-L-arginine methyl ester-induced hypertension:
      methodological considerations for studies of small arteries in hypertension.

PMID- 8557959
TI  - The relationships between left ventricular mass and daytime and night-time blood
      pressures: a meta-analysis of comparative studies.
AB  - OBJECTIVE: To review the literature to examine critically the assertion that
      night-time blood pressure is a better predictor of echocardiographic left
      ventricular mass than daytime blood pressure, and that left ventricular mass is
      inversely related to the day-night blood pressure difference. STUDY SELECTION:
      Published studies in which left ventricular mass (index) of normotensive or
      hypertensive individuals, or both, was related to automated blood pressure
      measurement during the day and night, or their difference, or both. RESULTS OF
      DATA ANALYSIS: The meta-analysis of 19 comparative studies, involving 1223
      participants, indicates that the weighted correlation coefficient for the
      relationship between left ventricular mass (index) and systolic night-time blood
      pressure (0.44; 95% confidence limit 0.39-0.48) is not significantly different
      from the correlation with systolic daytime blood pressure (0.48; 95% confidence
      limit 0.44-0.52; P > 0.2). The corresponding correlation coefficients for
      diastolic blood pressure both average 0.37. In half of the eight studies in which
      the association between left ventricular mass (index) and the day-night
      difference in blood pressure was analysed, investigators found no significant
      relationship between those variables; in the others, the variance of the mass
      (index) that can be explained by the blood pressure difference is 15% at the
      most. CONCLUSION: The overall analysis suggests that night-time blood pressure is
      not a significantly better predictor of left ventricular mass than daytime blood
      pressure is, and that the relationship to the day-night blood pressure difference
      is not a unanimous finding and is only ever weakly significant.

PMID- 8557960
TI  - Characteristics and expression of transforming growth factor-beta receptor
      subtypes on vascular smooth muscle cells from spontaneously hypertensive rats.
AB  - OBJECTIVE: To investigate the characteristics and expression of transforming
      growth factor (TGF)-beta receptor subtypes on vascular smooth muscle cells (VSMC)
      from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY)
      rats. METHODS: The effects of TGF-beta 1 on DNA synthesis were evaluated by [3H]
      thymidine incorporation into quiescent VSMC plated at high (5 x 10(4) cells/cm2)
      or low (5 x 10(3) cells/cm2) cell density. Specific binding of TGF-beta to VSMC
      was assessed by incubation of the cells with [125I]-TGF-beta 1. Affinity
      labelling of receptor subtypes was achieved by exposure of the cells to [125I]
      TGF-beta 1 and cross-linking with disuccimidyl suberate. RESULTS: VSMC from SHR
      displayed a biphasic DNA synthesis response to TGF-beta 1 at high cell density,
      with DNA synthesis stimulated by low concentrations of TGF-beta 1 but not by high
      concentrations, whereas at low cell density there was a small increase in DNA
      synthesis in response to TGF-beta 1. TGF-beta 1 inhibited DNA synthesis in VSMC
      from WKY rats at both high and low cell densities. Binding assays revealed that
      VSMC from SHR had a larger number of TGF-beta receptors and a higher affinity for
      TGF-beta at high and at low cell densities. The affinity labelling with [125I]
      TGF-beta 1 revealed the presence of receptor subtypes with relative molecular
      masses of 280-300, 85, 70, 60 and 50 x 10(3) on vascular smooth muscle cells from
      both rat strains at high cell density. The abundance of the 85 x 10(3) molecular
      mass receptor subtype was greater in VSMC from SHR. The 85 x 10(3) molecular mass
      receptor subtype was not detected on VSMC from either strain at low cell density.
      CONCLUSION: The present results suggest a different expression of TGF-beta
      receptor subtypes on VSMC from SHR and WKY rats. These differences may account
      for the exaggerated proliferative response of VSMC from SHR to TGF-beta.

PMID- 8557961
TI  - The influence of perindopril and the diuretic combination
      amiloride+hydrochlorothiazide on the vessel wall properties of large arteries in
      hypertensive patients.
AB  - OBJECTIVE: To compare the cardiovascular effects of 6 months of treatment with
      the angiotensin converting enzyme inhibitor perindopril and with the diuretic
      combination amiloride+hydrochlorothiazide, and to study possible persistence of
      observed treatment effects after discontinuation of antihypertensive therapy.
      DESIGN: A placebo run-in period preceded a 6-month active-treatment phase in 41
      patients with essential hypertension, according to a double-blind, randomized,
      parallel-group design. Patients received either 4 mg perindopril or 2.5/25 mg
      amiloride+hydrochlorothiazide once a day. Patients were then studied for a 3
      month single-blind placebo run-out period. RESULTS: After 6 months of treatment,
      systolic blood pressure was reduced significantly by perindopril (supine by 11%,
      sitting by 10%) and by amiloride+hydrochlorothiazide (supine by 8%, sitting by
      12%). Diastolic blood pressure was also decreased significantly by perindopril
      (supine by 8%, sitting by 11%) and by amiloride+hydrochlorothiazide (supine by
      4%, sitting by 9%). Mean arterial pressure decreased significantly during
      treatment with perindopril (by 9%) and with amiloride+hydrochlorothiazide (by
      6%). Cardiac index increased with perindopril (by 6%), because of an increased
      stroke index (by 5%), but amiloride+hydrochlorothiazide did not change cardiac
      function. Systemic vascular resistance index decreased significantly more with
      perindopril (by 14%) than with amiloride+hydrochlorothiazide (by 8%). The
      distensibility of the common carotid artery was significantly enhanced by
      perindopril (by 16%), but not changed by amiloride+hydrochlorothiazide (1%
      difference). The difference between perindopril and amiloride+hydrochlorothiazide
      for carotid distensibility was statistically significant. The compliance of the
      common carotid artery tended to be increased more by perindopril (by 7%) than by
      amiloride+hydrochlorothiazide, which induced a 5% decrease in carotid compliance.
      After withdrawal of therapy, for both drugs, all treatment-induced changes were
      reversed to pretreatment values within 7 weeks. CONCLUSION: The distensibility of
      the elastic common carotid artery was increased by perindopril, but not by
      amiloride+hydrochlorothiazide. Large-artery properties of the muscular arteries
      and systemic vascular resistance improved with both drugs, but in general the
      changes were more pronounced with perindopril than with
      amiloride+hydrochlorothiazide. The present results indicate a more pronounced
      effect of perindopril at both macro- and microcirculatory levels, which will
      consequently lead to a larger decrease in cardiac afterload. After
      discontinuation of therapy all parameters returned to baseline values within 7
      weeks.

PMID- 8557962
TI  - No evidence for vascular remodelling during hypertension induced by chronic
      inhibition of nitric oxide synthase in Brattleboro rats.
AB  - OBJECTIVE: To examine the effects of hypertension induced by chronic inhibition
      of nitric oxide synthase with NG-nitro-L-arginine methyl ester (L-NAME) on the
      structure of mesenteric resistance arteries. DESIGN AND METHODS: Brattleboro rats
      were given L-NAME (0.01-0.05 mg/ml, equivalent to 10-50 mg/kg per day) in their
      drinking water for 2-3 weeks. On the day of the experiment, mean arterial
      pressure was measured directly using an intra-arterial catheter that had been
      implanted 2 days previously. Isolated mesenteric resistance arteries were set up
      in a pressure-perfusion myograph in a calcium-free physiological solution and
      subsequently fixed with glutaraldehyde, embedded in Araldite, sectioned and
      examined histologically. RESULTS: L-NAME administration increased mean arterial
      blood pressure in comparison with normotensive controls. No differences were
      found between the structural characteristics of mesenteric resistance arteries of
      first (pressurized diameter approximately 350 microns), second (approximately 270
      microns) or third (approximately 200 microns) order vessels isolated from
      normotensive rats and rats that had been treated with L-NAME. There were no
      significant correlations between mean arterial blood pressure and the variables
      of internal diameter, media thickness and media: lumen area ratio. CONCLUSIONS:
      Hypertension produced by chronic inhibition of nitric oxide synthase is not
      associated with remodelling of mesenteric resistance arteries in Brattleboro
      rats.

PMID- 8557963
TI  - Effects of exposure to high altitude on plasma endothelin-1 levels in normal
      subjects.
AB  - OBJECTIVE: To assess whether the hypoxia associated with exposure to high
      altitude affects plasma endothelin-1 levels, and whether changes in endothelin-1
      are related to those in systemic and pulmonary blood pressure. DESIGN: Eight
      normal subjects ascended Mount Everest to an altitude of 5050 m within a period
      of 8 days (study 1) and 10 ascended Mount Rosa in the Italian Alps to an altitude
      of 4559 m within 2 days (study 2). In study 1 systemic blood pressure, heart
      rate, haematocrit, haemoglobin oxygen saturation (evaluated by percutaneous
      oximetry) and venous plasma endothelin-1 were measured several times during the
      ascent, and twice more during the time spent at high altitude. In study 2 the
      same parameters as well as systolic pulmonary pressure by echocardiography were
      evaluated on the second day of resting at 4559 m. In both studies, data obtained
      during the expeditions were compared with those collected from the same subjects
      at sea level. RESULTS: In study 1 plasma endothelin-1 increased progressively up
      to 4240 m (from 1.8 +/- 0.1 pg/ml at sea level to 2.7 +/- 0.2 pg/ml) and
      decreased slightly thereafter; these increments were directly related to the
      decrements in percutaneous oxygen saturation, which, at that altitude, fell from
      98.6 +/- 0.2% at sea level to 80.8 +/- 0.4%. Blood pressure and haematocrit also
      rose in response to exposure to high altitude but these changes were not related
      to changes in endothelin-1. In study 2 the increments in plasma endothelin-1 were
      similar to those observed in study 1 and the changes again correlated with
      changes in oxygen saturation as well as with those in systolic pulmonary
      pressure. On average, systolic pulmonary pressure increased from 19 +/- 1 to 26
      +/- 1.9 mmHg, whereas systemic blood pressure and haematocrit were unchanged.
      CONCLUSION: Exposure to high altitude is associated with consistent increases in
      plasma endothelin-1. This is probably the result of augmented secretion of the
      peptide in response to hypoxia and may contribute to the physiological adaptation
      of the pulmonary circulation to this condition.

PMID- 8557964
TI  - Alterations in intracellular cations and cell membrane ATPase activity in
      patients with malignant hypertension.
AB  - OBJECTIVE: To determine whether cellular cation concentrations and cell membrane
      ATPase activity are altered in patients with malignant hypertension. DESIGN:
      Sixteen black patients with malignant hypertension were studied and compared with
      age- and sex-matched essential hypertensive and normotensive subjects. Calcium,
      magnesium, sodium and potassium concentrations and cell membrane Na,K-ATPase, Ca
      ATPase and Mg-ATPase activities were determined in platelets and erythrocytes.
      METHODS: Intracellular concentrations of total magnesium and calcium were
      measured by atomic absorption spectrophotometry, and those of sodium and
      potassium by flame photometry. Cell membrane ATPase activity was measured by a
      colorimetric method. RESULTS: The intracellular calcium level was significantly
      elevated and intracellular magnesium and potassium levels and cell membrane
      ATPase activity significantly decreased in the hypertensive group. These changes
      were more marked in patients with malignant hypertension than in patients with
      benign essential hypertension. In the malignant hypertensive group, mean arterial
      pressure was negatively correlated with intracellular magnesium and positively
      correlated with intracellular calcium and sodium levels. CONCLUSIONS: Cellular
      cation changes in malignant hypertension may be related to altered transmembrane
      transport mechanisms and activation of the renin-angiotensin system. These
      alterations may be more pronounced in the malignant than in the benign phase of
      hypertension.

PMID- 8557965
TI  - Dietary calcium, blood pressure and cell membrane cation transport systems in
      males.
AB  - OBJECTIVE: A double-blind, placebo-controlled parallel-group study was conducted
      on the effect of a high level of daily oral calcium supplementation (1 g
      elemental calcium given twice a day for 16 weeks) in normal male subjects on
      blood pressure, intracellular cationic concentrations and transmembrane cation
      transport systems, plasma total and ionized calcium, and calciotropic hormones.
      METHODS: After a 1-month run-in period with a limited intake of dairy products,
      the 32 subjects were allocated to a placebo or a calcium group. Placebo or 1 g
      elemental calcium was administered twice a day, in the morning and evening, for
      16 weeks. All subjects were investigated at baseline and after 1, 2, 4, 8 and 16
      weeks of placebo or calcium administration. RESULTS: Compared with the placebo
      group, standing systolic blood pressure was decreased in the calcium group,
      whereas the standing diastolic blood pressure tended to decrease. The changes in
      supine systolic and diastolic blood pressure did not differ between the placebo
      and calcium groups. Decreased intra-erythrocyte and intraplatelet sodium and
      calcium concentrations, an increased activity of platelet and erythrocyte sodium
      pump activity and a reduced membrane cholesterol content were observed in the
      calcium-treated subjects. Erythrocyte membrane surface and core microviscosity,
      however, did not change during calcium supplementation. Oral calcium
      supplementation in these men was accompanied by a reduction in the plasma
      concentrations of intact parathormone and 1,25-dihydroxyvitamin D3, and an
      increase in 24 h urinary calcium excretion, but no change in the plasma total
      calcium concentration, serum ionized calcium level, or plasma phosphate or 25
      hydroxyvitamin D3. The intra-erythrocyte and intraplatelet potassium and
      magnesium concentrations as well as the activities of the erythrocyte Na,Li
      countertransporter and Na,K-cotransporter, and sodium and potassium leakage did
      not change during calcium administration. CONCLUSIONS: The lowering of standing
      blood pressure seen in men with a high calcium intake is accompanied by a
      decrease in cytosolic free platelet calcium and total erythrocyte calcium, by a
      reduction in intraplatelet and intra-erythrocyte sodium concentration and
      erythrocyte membrane cholesterol and by an increase in the activity of the
      erythrocyte and platelet sodium-pump.

PMID- 8557966
TI  - Brain angiotensin II contributes to the development of hypertension in Dahl-Iwai
      salt-sensitive rats.
AB  - OBJECTIVE: To examine the role of brain angiotensin II in the development of salt
      induced hypertension in Dahl-Iwai salt-sensitive (DIS) rats. METHODS: Male DIS
      and Dahl-Iwai salt-resistant (DIR) rats aged 5 or 6 weeks were implanted with an
      intracerebroventricular cannula, and either chronic intracerebroventricular
      infusion of 5 micrograms/day CV-11974, a non-peptide type-1 angiotensin II
      receptor antagonist or artificial cerebrospinal fluid (aCSF) was started. The
      rats were fed a diet containing 8% sodium chloride. RESULTS: On day 11 or 12 of
      chronic infusion, DIS rats given CV-11974 intracerebroventricularly exhibited a
      significantly lower mean arterial pressure than DIS rats given aCSF
      intracerebroventricularly or intravenous infusion of CV-11974. In DIR rats,
      intracerebroventricular infusion of CV-11974 did not alter the mean arterial
      pressure. Sodium and water balances were similar in all of the groups. Plasma
      vasopressin and noradrenaline levels did not differ among the groups, although
      the plasma renin concentration was significantly lower in DIS rats given aCSF
      intracerebroventricularly. Arterial baroreflex control of heart rate and pressor
      response to intravenous injection of phenylephrine were not altered in rats given
      CV-11974 intracerebroventricularly. CONCLUSION: The integrity of the brain renin
      angiotensin system is necessary for the development of salt-induced hypertension
      in DIS rats.

PMID- 8557967
TI  - Angiotensin II receptor blockade in TGR(mREN2)27: effects of renin-angiotensin
      system gene expression and cardiovascular functions.
AB  - OBJECTIVE: To study the effect of angiotensin II receptor AT1 blockade on blood
      pressure, gene expression and pathomorphology of transgenic rats harbouring the
      mouse Ren-2 gene [TGR(mREN2)27], that develop fulminant hypertension while
      exhibiting suppressed components of the circulating renin-angiotensin system.
      DESIGN: TGR(mREN2)27 were treated orally with the newly developed AT1-specific
      angiotensin receptor antagonist Telmisartan, 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi
      1H-benzimidazol]-1'-yl) methyl]-[1,1'-biphenyl]-2-carboxylic acid, in three doses
      (0.1, 1 and 3 mg/kg body weight) for 9 weeks. METHODS: The concentrations of the
      renin-angiotensin system components were analysed in plasma and tissues by
      radioimmunoassay. Messenger RNA levels for the angiotensinogen and renin genes
      were quantified by RNAase protection assay in several tissues. Heart hypertrophy
      and kidney morphology and function were monitored at the end of the treatment.
      RESULTS: In contrast to 0.1 mg/kg, 1 and 3 mg/kg Telmisartan normalized tail
      blood pressure measured once a week. Plasma renin and angiotensin II
      concentration increases were dose-dependent. The renin-angiotensin system genes
      in various cardiovascular organs were differentially regulated by angiotensin II
      receptor blockade. Treatment with Telmisartan stimulated angiotensinogen gene
      expression in the liver, kidney and heart, whereas it remained unchanged in the
      hypothalamus, thymus and adrenal gland. In the kidney, the expression of the
      endogenous, but not of the mouse Ren-2 gene, was increased in parallel to the
      renin concentration. Telmisartan reduced the severe glomerulosclerosis and
      proteinuria as well as cardiac hypertrophy observed in untreated TGR(mREN2)27
      even with the lowest dose of 0.1 mg/kg, at which the blood pressure of the rats
      still exceeded 225 mmHg and the plasma renin-angiotensin system parameters were
      unchanged. CONCLUSION: From these experiments using a specific antagonist we can
      conclude that high blood pressure in TGR(mREN2)27 is angiotensin II-dependent.
      Furthermore, the expression of the renin-angiotensin system genes seems to be
      regulated not only by blood pressure and the plasma renin-angiotensin system but
      also by other, tissue-specific mechanisms. Pathomorphological changes in the
      kidney and in the heart do not seem to be caused by the systemic hypertension
      exclusively, but are also influenced by angiotensin II directly.

PMID- 8557968
TI  - Cardiovascular response to mental stress in offspring of hypertensive parents:
      the Dutch Hypertension and Offspring Study.
AB  - OBJECTIVE: To compare blood pressure-regulating mechanisms during mental stress
      in two groups of offspring with contrasting risk for hypertension. DESIGN:
      Cardiovascular reactivity to two different types of mental stressors was studied
      in adolescents and young adults with two hypertensive or two normotensive
      parents. The two tasks used were intended to evoke either a predominantly
      adrenergic cardiac response (a memory search task) or a predominantly vascular
      response (a reaction-time task with visual search and tone avoidance). METHODS:
      Blood pressure and heart rate were recorded at rest and during stress. To study
      adaptations of the cardiovascular system to mental stress, cardiac output, total
      peripheral resistance and indices of vagal and sympathetic influences on the
      heart were measured. RESULTS: The reactivity of systolic blood pressure (SBP) to
      the memory search task was significantly higher in offspring of hypertensive
      parents, which resulted in a longer recovery after the task. In contrast, during
      the reaction-time task, offspring of hypertensive parents had a significantly
      enhanced reactivity of peripheral resistance, but no differences in heart rate or
      blood pressure response were observed. No differences between the two groups were
      found in sympathetic or vagal activity during either task measured by the ratio
      of pre-ejection time and left ventricular ejection time, and respiratory sinus
      arrhythmia, respectively. CONCLUSION: Apart from a higher reactivity of SBP
      during the memory search task, no other indications supporting the presence of
      hyperadrenergic activation of the heart in early primary hypertension were found.
      On the contrary, the results of the present study support the hypothesis that
      blood pressure responses in prehypertensive subjects are characterized by
      enhanced vasoconstriction rather than by increased cardiac output.

PMID- 8557969
TI  - Risk of fatal stroke according to blood pressure level: an 18-year follow-up of
      the Oslo Study.
AB  - OBJECTIVE: To determine how blood pressure level predicts the incidence of fatal
      stroke. DESIGN: The Oslo Study is a prospective cohort study of preventive and
      epidemiological aspects of cardiovascular disorders in middle-aged men. Of 25,915
      men invited, 16,209 aged 40-49 years attended the screening. A 7% random sample
      of men aged 20-39 years were also invited to attend. METHODS: The screening
      started in May 1972 and the analysis presented is an 18-year follow-up for fatal
      strokes. Men with a history of stroke were excluded from the analyses. RESULTS:
      Of 16,173 men with no history of stroke 85 died from stroke. Results from Cox
      proportional hazards regression analysis confirm diastolic (DBP) and systolic
      blood pressure (SBP) as strong independent risk factors of fatal stroke, with DBP
      being the stronger predictor. Analyses of risk of fatal stroke by quintile values
      show SBP to give significantly increased risk from the third quintile (136 mmHg),
      and DBP from the fifth quintile (95 mmHg) relative to the first quintile. No
      levelling off at highest levels can be seen when analysing decile values. No J
      shape of the curve was evident. Men on drug treatment for hypertension with no
      stroke history (n = 440) had 4.7-fold (crude) and 2.8-fold (adjusted for age and
      DBP) the rate of stroke mortality of men not on drug treatment for hypertension.
      CONCLUSION: DBP was a stronger predictor than SBP, with increasing risk from the
      fifth quintile of DBP and the third quintile of SBP. Men on drug treatment for
      hypertension at screening were at increased risk during the follow-up period,
      indicating that their treatment did not sufficiently reduce their risk of stroke.

PMID- 8557970
TI  - Complications and survival of 315 patients with malignant-phase hypertension.
AB  - OBJECTIVE: To investigate the factors affecting survival in patients with
      malignant hypertension by analysing the prognosis of all of the patients referred
      to the City Hospital, Birmingham, with malignant hypertension since 1965.
      RESULTS: We identified 315 patients with malignant hypertension (211 men, 104
      women; mean age +/- SD 49.4 +/- 12.7 years). Of those patients, 219 were
      Caucasian, 55 were black and 41 were Asian. Black patients had greater renal
      impairment and higher blood pressures at presentation. After a median follow-up
      period of 33 months (range 1-389), 126 patients (40.0%) were still alive, 126
      patients (40.0%) were dead, 10 patients (3.2%) were receiving chronic
      haemodialysis and 53 patients (16.8%) were lost to follow-up. Mean follow-up
      blood pressures in the patients who died were significantly higher than in those
      who lived. Median survival times for Caucasian, black and Asian patients were
      121.0, 30.4 and 107.5 months, respectively, with the lowest survival time being
      that of black patients. There was a lower median survival time among patients
      with proteinuria and high serum urea (> 10 mmol/l) and creatinine (> 200 mumol/l)
      levels at presentation and if left ventricular hypertrophy was detected on the
      electrocardiogram, but there was no difference in median survival time between
      those with and without haematuria, nor between non-smokers and current or former
      smokers. The most common causes of death were renal failure (39.7%), stroke
      (23.8%), myocardial infarction (11.1%) and heart failure (10.3%). Median survival
      times for the patients who presented before 1970, during 1970-1979 and during
      1980-1989 were 39.2, 68.6 and 144.0+ months, respectively, demonstrating an
      improved survival time for the patients who were diagnosed after 1980. Using
      multivariate Cox's proportional hazards analyses, the duration of known
      hypertension and serum urea level at presentation were found to be the main
      predictors of survival. CONCLUSION: Malignant hypertension remains a disease with
      a poor overall prognosis, namely progression to death or chronic renal
      haemodialysis. The prognosis has improved with recent advances in therapy, with a
      5-year survival of 74% of patients. The poor outlook for black patients could be
      explained by their late presentation with severe hypertension and the higher
      prevalence of renal impairment in this group.

PMID- 8557971
TI  - Influence of non-steroidal anti-inflammatory drugs on renal function and 24h
      ambulatory blood pressure-reducing effects of enalapril and nifedipine
      gastrointestinal therapeutic system in hypertensive patients.
AB  - OBJECTIVE: To evaluate the influence of non-steroidal anti-inflammatory drugs
      (NSAIDs; aspirin and indomethacin) on the renal and antihypertensive effects of
      enalapril and nifedipine gastrointestinal therapeutic system (GITS) in patients
      with essential hypertension. DESIGN AND METHODS: In a crossover study, 18
      patients on an unrestricted-salt diet were randomly assigned to receive either
      enalapril (20-40 mg/day) or nifedipine-GITS (30-60 mg/day) for 4-8 weeks,
      followed by aspirin (100 mg/day for 2 weeks) and then indomethacin (75 mg/day for
      1 week). Blood pressure was measured by 24h ambulatory monitoring. RESULTS:
      Enalapril and nifedipine-GITS significantly reduced blood pressure compared with
      placebo. Aspirin did not alter the antihypertensive effect of either drug.
      Indomethacin attenuated (by 45%) the antihypertensive effect of enalapril
      throughout the 24h period of evaluation, but did not interfere with the effect of
      nifedipine. Furthermore, indomethacin significantly reduced the fractional
      excretion of sodium and plasma levels of prostaglandins in a similar way when
      added to either the enalapril or the nifedipine regimen. CONCLUSIONS:
      Vasodilatory prostaglandins are probably involved in the antihypertensive effects
      of enalapril but not of nifedipine, and this interaction seems to be independent
      of any indomethacin-induced decrease in renal sodium excretion. Nifedipine may be
      an appropriate drug to treat hypertensive patients requiring concomitant therapy
      with NSAID.

PMID- 8557972
TI  - Intensified antihypertensive therapy is associated with improved survival in type
      1 diabetic patients with nephropathy.
AB  - OBJECTIVE: To determine the prognosis of treated hypertensive type 1 (insulin
      dependent) diabetic patients with overt nephropathy. DESIGN: A controlled,
      prospective, parallel, 5-year follow-up trial. SETTING: The tertiary care centre
      of the Heinrich Heine University Hospital in Dusseldorf, Germany. PATIENTS AND
      INTERVENTIONS: A sequential sample of 91 hypertensive patients with overt
      diabetic nephropathy participated in a diabetes treatment programme. Thereafter
      45 patients received intensified antihypertensive therapy including blood
      pressure self-monitoring and self-adjustment of antihypertensive drug treatment
      with the goal of permanent normalization of blood pressure values below 140/90
      mmHg. The remaining 46 patients were administered routine antihypertensive
      therapy and formed the control group. At baseline both groups were comparable in
      age, sex, metabolic control and renal function. The groups differed at baseline
      in their duration of diabetes and blood pressure values, which were higher in the
      intensified antihypertensive therapy group. OUTCOME MEASURES: Total mortality and
      the need for renal replacement therapy. MAIN RESULTS: Blood pressure control was
      significantly improved in patients who were subjected to intensified
      antihypertensive therapy, whereas it deteriorated in the group of patients who
      received routine antihypertensive therapy. At follow-up, primary end points of
      the study occurred in five (11%) patients of the intensified therapy group and in
      19 (41%) patients of the routine therapy group. According to life table analysis,
      intensified antihypertensive therapy was associated with less frequent primary
      end points (P = 0.0058) and longer survival (P = 0.01). The differences between
      the groups remained significant after adjustment for covariates in the
      proportional hazards model. CONCLUSION: Participation in a treatment programme
      aimed at intensification of antihypertensive therapy is associated with a
      reduction of mortality in hypertensive type 1 diabetic patients with overt
      nephropathy.

PMID- 8557973
TI  - CD28 expression is not essential for positive and negative selection of
      thymocytes or peripheral T cell tolerance.
AB  - Thymocyte development requires positive selection of clones that can recognize Ag
      presented by MHC molecules and negative selection of clones that are self
      reactive. However, the costimulatory signals required for negative selection and
      cell death, or positive selection and the transition to the peripheral lymphoid
      system, are not well understood. Many molecular interactions that are important
      for T cell activation have also been found to play a role in thymocyte
      development. The importance of the CD28/B7 interaction in the activation of
      mature T cells and recent observations that CD28 may play a role negative
      selection of developing CD4+CD8+ thymocytes suggest that CD28 may also be
      involved in development and maintenance of T cell tolerance. CD28-deficient mice
      were crossed to alpha beta and gamma delta TCR transgenic as well as H-2k Mlsc
      bearing animals and were used to address the role of CD28 in positive and
      negative selection of developing T cells. The CD28-deficient animals demonstrated
      no obvious deficiency in either positive or negative selection of developing
      thymocytes. However, when mixed bone marrow chimeras were created with cells
      derived from both CD28-deficient and wild-type mice, the CD28+ T cells had a
      selective advantage over the CD28-deficient T cells. Therefore, it appears that
      CD28, although not essential for the selection of T cells during development, may
      allow for additional signals that increase the efficiency of selection and/or
      expansion of peripheral T cell populations.

PMID- 8557974
TI  - Transport of anti-sperm monoclonal IgA and IgG into murine male and female
      genital tracts from blood. Effect of sex hormones.
AB  - Ab levels in the genital tract may be important in fertility and in preventing
      sexually transmitted diseases. In this study, 125I-labeled polymer or monomer mAb
      IgA (C4pIgA or C4mIgA) and IgG2b (C4IgG) to murine lactate dehydrogenase C4 and a
      polymer mAb IgA (nplgA) not cross-reacting with mouse sperm were intravenously
      injected into BALB/c mice, and the relative distribution of these Abs was
      determined. Polymer IgA was transported much more efficiently into the genital
      tract, trachea, and duodenum of both sexes than C4IgG and C4 mIgA (p < 0.01). The
      transport of polymer IgA (C4pIgA and npIgA) into the male genital tract greatly
      increased following orchiectomy (p < 0.01); this change was not affected by
      testosterone, suggesting that the unknown regulatory factor(s) from the testis
      may suppress polymer IgA transport. However, the transport of polymer IgA into
      female genital tissues was significantly decreased by ovariectomy (p < 0.01);
      this decline can be rectified by beta-estradiol but not progesterone treatment,
      suggesting that estradiol may stimulate polymer IgA transport. Furthermore, the
      transport of C4IgG into tissues of the Fallopian tubes and the uterus was
      significantly decreased by treatment with progesterone (p < 0.01). Together,
      these findings indicate that serum polymer IgA can be transported selectively
      into the genital tracts of both sexes, that this transport is strongly under the
      control of gonads, and that transport of IgG into the Fallopian tubes and uterus
      is down-regulated by progesterone.

PMID- 8557975
TI  - MEK1 and the extracellular signal-regulated kinases are required for the
      stimulation of IL-2 gene transcription in T cells.
AB  - TCR engagement stimulates the activation of the protein kinase Raf-1. Active Raf
      1 phosphorylates and activates the mitogen-activated protein (MAP)
      kinase/extracellular signal-regulated kinase kinase 1 (MEK1), which in turn
      phosphorylates and activates the MAP kinases/extracellular signal regulated
      kinases, ERK1 and ERK2. Raf-1 activity promotes IL-2 production in activated T
      lymphocytes. Therefore, we sought to determine whether MEK1 and ERK activities
      also stimulate IL-2 gene transcription. Expression of constitutively active Raf-1
      or MEK1 in Jurkat T cells enhanced the stimulation of IL-2 promoter-driven
      transcription stimulated by a calcium ionophore and PMA, and together with a
      calcium ionophore the expression of each protein was sufficient to stimulate NF
      AT activity. Expression of MEK1-interfering mutants inhibited the stimulation of
      IL-2 promoter-driven transcription and blocked the ability of constitutively
      active Ras and Raf-1 to costimulate NF-AT activity with a calcium ionophore.
      Expression of the MAP kinase-specific phosphatase, MKP-1, which blocks ERK
      activation, inhibited IL-2 promoter and NF-AT-driven transcription stimulated by
      a calcium ionophore and PMA, and in addition, MKP-1 neutralized the
      transcriptional enhancement caused by active Raf-1 and MEK1 expression. We
      conclude that the MAP kinase signal transduction pathway consisting of Raf-1,
      MEK1, and ERK1 and ERK2 functions in the stimulation IL-2 gene transcription in
      activated T lymphocytes.

PMID- 8557976
TI  - Delineation of IL-5 domains predicted to engage the IL-5 receptor complex.
AB  - IL-5 is an interdigitating homodimeric glycoprotein and a member of the helical
      bundle family of cytokines. IL-5 is a potent activator of eosinophils and a
      specific promoter of their differentiation. This activity has implicated IL-5 in
      the pathogenesis of asthma and allergic disease. A detailed understanding of IL-5
      structure and function is required to develop immunomodulators of IL-5-mediated
      inflammatory responses. We generated a panel of neutralizing anti-IL-5 mAbs which
      were used to map functional domains on IL-5. In addition, the nucleotide
      sequences for human IL-5, murine IL-5, rat IL-5, and eight human/murine IL-5
      chimeras were engineered and expressed in COS-7 cells. These recombinant
      cytokines and mAbs were used in TF-1 bioassays to identify five functional
      epitopes on the tertiary structure of IL-5. Residues responsible for the species
      specific activity of human IL-5 were identified with the murine BCL1 bioassay.
      One set of epitopes cluster around the helix A-loop 2 region, which is predicted
      to engage the IL-5 receptor beta-chain. The second set of epitopes as well as the
      species specificity domain cluster around the loop 3-helix D region, which is
      predicted to engage the IL-5 receptor alpha-chain. Together, these analyses
      target the A/D helical face of IL-5 as the region involved in receptor
      engagement.

PMID- 8557977
TI  - Deletional mapping of fifteen mouse VH gene families reveals a common
      organization for three Igh haplotypes.
AB  - In addition to the content of germ-line variable gene segments, the organization
      of V genes has been implicated in the development of the Ab repertoire. We have
      searched the expressed VH genes of BALB/c mice for additional VH gene families
      and utilized deletion mapping to explore the extent of VH gene family
      interspersion. We have identified and characterized one new VH gene family (VH15)
      and extended our previous studies of the Igha and Ighb haplotypes to include a
      third haplotype (Ighj) using a newly developed panel of pre-B cell lines (CXCB
      cell lines). We conclude that the Igha, Ighb, and Ighj haplotypes have a similar
      Igh-V locus structure. A refined deletional map for 15 VH gene families and an
      individual member of the VHSM7 family (H10) has been constructed based on the
      deletion profiles of 72 rearranged heavy chain loci. These results demonstrate
      previously unrecognized examples of interspersion among members of the VHS107,
      VH10, and VHSM7 families.

PMID- 8557978
TI  - Differential effects of CTLA-4 substitutions on the binding of human CD80 (B7-1)
      and CD86 (B7-2).
AB  - CTLA-4 expressed on activated T cells binds to CD80 (B7-1) and CD86 (B7-2)
      molecules present on APC with high avidity and appears to deliver a negative
      regulatory signal to the T cell. We have investigated the kinetics of CTLA-4
      binding to CD80 and CD86, together with the effects of selected CTLA-4 mutations
      on binding activity. The dissociation constants (Kd) for binding of CTLA-4-Ig to
      CD80 and CD86 transfectants were 8.1 and 6.7 nM, respectively. Surface plasmon
      resonance was used to determine kinetic parameters of CTLA-4-Ig binding to CD80
      Ig and CD86-Ig fusion proteins and revealed enhanced association (ka) and
      dissociation (kd) rate constants for CD86-Ig compared with CD80-Ig. Furthermore,
      CD80-Ig and CD86-Ig fusion molecules demonstrated variable abilities to cross
      compete for binding to several modified forms of CTLA-4-Ig. Differential binding
      of CD80 and CD86 to CTLA-4 was further revealed by analysis of 10 discrete CTLA-4
      mutants. Five single amino acid substitutions within the CTLA-4 MYPPPY domain
      exerted modest effects on CD80 binding, but each of these substitutions
      completely abrogated CD86 binding. In addition, substitutions just N-terminal of
      the MYPPPY region, and within the CDR1-like region of CTLA-4, eliminated both
      CD80 and CD86 binding. Hence, CD80 and CD86 bind with different
      association/dissociation kinetics to similar, but distinct, sites on CTLA-4.

PMID- 8557979
TI  - Inhibition of IFN-stimulated gene expression and IFN induction of cytolytic
      resistance to natural killer cell lysis correlate with E1A-p300 binding.
AB  - Treatment of target cells with IFN induces resistance to NK cell lysis. This
      process is blocked by expression of E1A gene products in adenovirus (Ad)-infected
      and Ad-transformed cells. We compared the ability of adenovirus serotype 5 (Ad5)
      E1A exon 1 mutants to inhibit the induction of cytolytic resistance by IFN and
      block IFN-stimulated gene expression with their capacity to bind the cellular
      proteins p105 (retinoblastoma gene product), p107, and p300. E1A mutants that did
      not express conserved region 3 (CR3; residues 138-184) or contained deletions in
      the nonconserved regions between residues 26-35 or 86-120, bound p105, p107, and
      p300 and were not impaired in their capacity to block IFN-stimulated gene
      expression or IFN's induction of cytolytic resistance. E1A mutants with deletions
      in CR2 (residues 121-138) could not bind p105 or p107, but blocked IFN-stimulated
      gene expression and IFN's induction of cytolytic resistance. In contrast, mutants
      in CR1 or the N-terminal nonconserved region (residues 2, 4-25, and 48-60), which
      define E1A's binding site for p300, were unable to block either IFN-stimulated
      gene expression or IFN's induction of cytolytic resistance. We conclude that
      E1A's capacity to block both IFN-stimulated gene expression and IFN's induction
      of cytolytic resistance appears to be transduced through a pathway that involves
      E1A-p300 binding. The capacity of E1A to block IFN's induction of cytolytic
      resistance is probably secondary to E1A's more general ability to inhibit IFN
      stimulated gene expression.

PMID- 8557980
TI  - Evolution of hemopoietic ligands and their receptors. Influence of positive
      selection on correlated replacements throughout ligand and receptor proteins.
AB  - The rates of amino acid replacement in cytokines and their receptors are high and
      vary considerably. To determine whether this reflects the action of positive
      selection, rates of nonsynonymous DNA substitution were examined and found to
      exceed the synonymous substitution rate in certain exons of rodent IL-3,
      granulocyte-macrophage stimulating factor, and IL-4. To determine the extent to
      which positive selection could account for correlations between the amino acid
      replacement rates of hemopoietins and their receptors, rates were examined in
      various domains: the correlation with ligand rate was not confined to the ligand
      binding domain of the receptor, but extended into the transmembrane and
      cytoplasmic domains and even to leader peptide domains of both ligand and
      receptor. As the majority of these replacements are unlikely to be strongly
      advantageous, different levels of both positive and purifying selection
      contribute to the extensive variation in hemopoietin/receptor evolutionary rates.
      Changes in a few residues critical for ligand-receptor interaction may be
      followed by changes of lesser selective importance in both molecules:
      replacements of growth hormone residues that form hydrogen or salt bridges with
      the receptor occur in lineages in which there are many concurrent replacements. A
      ligand/receptor rate correlation is not found between the seven-transmembrane
      receptors and their ligands, whose mature forms are often short and completely
      conserved. This study predicts that a minority of concurrent evolutionary changes
      in hemopoietins and their receptors reflect directly compensatory changes.

PMID- 8557981
TI  - Analysis of antigen binding and idiotypic expression by antibodies with
      polyglycine-replaced complementarity-determining regions.
AB  - We investigated the feasibility and usefulness, for structure-function studies,
      of removing the side chains of entire complementarity-determining regions (CDRs)
      of Abs by replacement with polyglycine. The CDRs of a murine Ab specific for p
      azophenylarsonate (Ars) were replaced with polyglycine, one CDR at a time and in
      combinations, by oligonucleotide-directed mutagenesis of the V region genes.
      Mutant Abs were expressed in transfected hybridoma cells and analyzed for Ars
      binding and for idiotypic expression. The results suggest that, except for the
      longest CDRs, polyglycine replacement does not alter the general structure of the
      Ab molecule. However, for analysis of functional contributions of a CDR, the
      polyglycine replacement method appears to be most useful for CDRs with extended
      structures whose replacement by polyglycine does not affect the structure of
      other parts of the variable regions. In the current studies, such CDRs were CDR1
      of the heavy chain (H1) and CDR2 of the light chain (L2). The polyglycine
      replacement of L2, which does not contain an Ag-contacting residue, allowed the
      formation of an Ars binding Ab. Furthermore, this mutant Ab revealed previously
      uncharacterized contributions of L2 to idiotypic expression. Polyglycine
      replacement of H1 abolished Ars binding as expected, because H1 contains an Ag
      contacting residue. However, introduction of the contacting residue (Asn) on the
      polyglycine-replaced H1 background restored the ability of the Ab to bind Ars.
      The results suggest that polyglycine replacement of CDRs can provide structural
      information that complements and extends the information obtained by other
      methods.

PMID- 8557982
TI  - Molecular cloning and characterization of murine IL-12 genes.
AB  - IL-12 is a heterodimeric cytokine composed of two covalently linked chains, p40
      and p35. p40 expression appears to be restricted to monocytes/macrophages and B
      cells and is highly regulated, while p35 is more ubiquitously and constitutively
      expressed. To investigate the mechanism involved in the regulation of IL-12
      expression, we molecularly cloned and characterized the murine p40 and p35 genes.
      The p40 gene spans over 14 kb, consists of eight exons and seven introns, and was
      shown to be localized on chromosome 11A5-B2 by fluorescence in situ
      hybridization. A single major transcription initiation site was detected by
      primer extension analysis, and a TATA box was found at approximately 30 bp
      upstream from the transcription initiation site. The 5' flanking region preceding
      the transcription initiation site induced the enhanced expression of a
      promoterless reporter gene after LPS stimulation when transfected into a
      macrophage-like cell line. In contrast, the p35 gene spans over 8 kb and consists
      of seven exons and six introns on chromosome 6C, and multiple transcription
      initiation sites were detected. The 5' flanking region lacks canonical TATA and
      CAAT boxes at the appropriate position, but, instead, contains GC-rich sequences
      and constitutively mediated promoter activity when placed upstream of a
      promoterless reporter gene and transfected into a B cell lymphoma cell line.
      Thus, the characteristics of promoter regions of p40 and p35 genes are quite
      different, and this would account for the different regulations of p40 and p35
      expression.

PMID- 8557983
TI  - Toxoplasma gondii infection induces specific nonresponsiveness in lymphocytes
      bearing the V beta 5 chain of the mouse T cell receptor.
AB  - We recently reported a superantigen activity associated with Toxoplasma gondii
      tachyzoites that in vitro induces preferential expansion of V beta 5+ T
      lymphocytes following parasite stimulation of nonimmune cells. In the experiments
      presented in this work, V beta 5+ lymphocyte function was examined ex vivo using
      mice undergoing chronic and acute infection with the avirulent parasite strain
      ME49 or acutely infected with the attenuated mutant ts-4. Cells bearing the TCR V
      beta 5 chain were found to be increased by 1.5- to twofold during acute
      infection, whereas during the chronic phase, modest decreases (approximately 20%)
      in cells of the latter subset were observed. When splenocytes from chronically
      infected animals were stimulated in vitro with tachyzoites, the preferential
      expansion of V beta 5+ lymphocytes seen using cells from normal mice was not
      observed. Furthermore, when purified T lymphocytes were cultured with plate-bound
      V beta 5-specific mAb, we found that in contrast to normal and acutely infected
      animals, cells from chronically infected and ts-4-vaccinated mice were
      nonresponsive to TCR-induced stimulation (70 to 90% reduction relative to normal
      cells). In control experiments, mAb to CD3 and V beta 8 elicited normal responses
      in the same animals. Similarly, in contrast to normal splenocytes, cells from
      chronically infected mice failed to produce IFN-gamma in response to anti-V beta
      5 mAb. These data indicate that V beta 5+ cells are rendered nonresponsive as a
      result of in vivo encounter with T. gondii, and as such they provide the first
      demonstration of V beta-specific anergy induced by a protozoan parasite.

PMID- 8557984
TI  - Endogenous IL-12 is necessary for rejection of P815 tumor variants in vivo.
AB  - Although murine tumor cells have been transfected to express a multitude of
      different cytokines and shown to be rejected in vivo, it is unclear which of
      these factors might be useful to facilitate tumor Ag immunization schemes. A
      study of the normal immune mechanisms involved in tumor rejection when it
      naturally occurs should reveal critical signals for generation of antitumor CTL
      in vivo. The highly transfectable variant of P815, P1.HTR, was found to be
      rejected in the hind footpads by approximately one-third of syngeneic DBA/2 mice.
      Analysis of draining popliteal lymph nodes revealed a large influx of CD4+ and
      CD8+ T lymphocytes in all mice, indicating that a failure to reject was not due
      to the complete absence of an inflammatory response. However, although IL-2 and
      IL-3 were produced by lymph node cells from all mice, only approximately one
      third generated a high IFN-gamma response. IL-4 was not detected. To explore a
      role for IL-12 in the induction of the IFN-gamma-producing phenotype, a histidine
      tagged IL-12 fusion protein was expressed in mammalian cells and purified by
      nickel-chelate chromatography, and a rabbit antiserum was produced.
      Neutralization of IL-12 in vivo eliminated the high IFN-gamma response and
      prevented rejection of P1.HTR tumors and also of a more immunogenic tum- variant
      of P815, P198. Conversely, exogenous IL-12 delivered early during challenge with
      P1.HTR cells induced high IFN-gamma production and resulted in tumor rejection in
      most mice. Therefore, endogenous IL-12 is vital for the rejection of these tumors
      when it naturally occurs, supporting a role for exogenous administration of this
      cytokine to favor a Th1-like phenotype in the immunotherapy of cancer.

PMID- 8557985
TI  - The antitumoral effect of the immunomodulator AS101 and paclitaxel (Taxol) in a
      murine model of lung adenocarcinoma.
AB  - The immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate (AS101) has
      been shown to possess antitumoral properties in several murine models. In the
      present study, we demonstrate a synergistic in vivo antitumor effect of AS101 and
      Taxol against early stage Madison 109 lung adenocarcinoma. Treatment with optimal
      doses of Taxol (25 and 17 mg/kg) and AS101 (0.5 mg/kg) resulted in 66.6 and 43.3%
      cures. We propose that the antitumor effect is the result of both a direct and
      indirect effect of the drugs on tumor cells. AS101 and Taxol directly inhibited
      clonogenicity of M109 cells in a synergistic dose-dependent manner. Exposure of
      M109 cells to clinically achievable concentrations of Taxol and AS101 produced a
      synergistic internucleosomal DNA fragmentation associated with programmed cell
      death. We suggest that AS101 renders tumor cells more susceptible to chemotherapy
      in general and to Taxol in particular, partly by increasing the wild-type p53
      protein expression that is required for efficient execution of the death program.
      Moreover, we demonstrate a synergistic effect of AS101 and Taxol in increasing
      the tumoricidal activity of macrophages. This activity is produced by nitric
      oxide secretion. The synergistic antitumoral effects of AS101 and Taxol were
      partly ablated both in vitro and in vivo by inhibition of nitric oxide synthase.
      These findings indicate that AS101 in combination with Taxol may be a promising
      antitumor drug, and illustrate the mechanism of action of both drugs when acting
      synergistically. Phase II clinical trials have been initiated using AS101 in
      combination with Taxol.

PMID- 8557986
TI  - Herpes simplex virus type 1-mediated up-regulation of IL-12 (p40) mRNA
      expression. Implications in immunopathogenesis and protection.
AB  - In this report we investigated whether induction of IL-12 occurs in response to
      herpes simplex virus (HSV) infection of the mouse eye, which may serve to
      regulate the nature of the subsequent immune response. The data show early
      induction and continued maintenance of IL-12 (p40) mRNA in the cornea and
      draining lymph node upon ocular infection with HSV. Using a very sensitive
      radioimmunoassay technique, IL-12 (p40) protein also was detected in the cornea
      upon ocular HSV infection. Unfractionated splenocytes and enriched populations of
      dendritic cells, macrophages, and neutrophils all responded to HSV infection in
      vitro by up-regulating the expression of IL-12 (p40) mRNA. However, cultured
      corneal cells failed to generate IL-12 (p40) upon exposure to HSV. The data
      indicate that inflammatory cells that infiltrate the cornea in response to HSV-1
      infection are the main source of IL-12 in the eye. Our results are consistent
      with the hypothesis that IL-12 induction in the eye acts as a triggering event
      that biases HSV-specific immunity to a type 1 T cell response, which, in the
      environment of the eye, culminates in an immunopathologic disease.

PMID- 8557987
TI  - Generation of primary tumor-specific CTL in vitro to immunogenic and poorly
      immunogenic mouse tumors.
AB  - This study investigated the generation of primary tumor-specific CTL activity in
      vitro to several mouse tumors. We report that the development of optimal primary
      tumor-specific CTL to the P815 mastocytoma, the EL4 thymoma, and the Lewis lung
      carcinoma is dependent on tumor Ags, on enhancement of T cell costimulation by
      B7.1, and on exogenous T helper activity in the form of IL-2 and IL-4. A
      relatively low concentration of IL-2 and IL-4 was required to limit the induction
      of lymphokine-activated killer cells. In the case of P815, the CTL were directed
      toward molecularly defined tumor rejection Ags. These primary cultures yielded
      long term T cell lines that were heterogeneous in fine tumor Ag specificity and
      in cytokine production.

PMID- 8557988
TI  - B7-1 is superior to B7-2 costimulation in the induction and maintenance of T cell
      mediated antileukemia immunity. Further evidence that B7-1 and B7-2 are
      functionally distinct.
AB  - Although intact, viable tumor cells rarely induce a clinically significant immune
      response in vivo, immunogenicity can be elicited by irradiated tumor cells that
      protect against subsequent challenge with wild-type intact viable tumor cells.
      Genetic modification of murine tumor cells, by transfection of cDNAs encoding
      either cytokines, MHC molecules, or costimulatory molecules, has been capable of
      inducing antitumor immunity. We and others have previously demonstrated that
      expression of the B7-1 costimulatory molecule, in either immunogenic or
      nonimmunogenic tumors, can protect against subsequent challenge with wild-type
      tumor cells. In this work, using a murine model of acute myeloid leukemia, we
      demonstrate that the B7-1 costimulatory molecule is superior to the B7-2 molecule
      in its capacity to protect against wild-type tumor challenge and eradicate
      minimal residual disease. These results provide compelling evidence that the B7-1
      and B7-2 costimulatory signals are functionally distinct, thus resulting in
      clinically significant differences in the induction of antitumor immunity in
      vivo.

PMID- 8557989
TI  - Expression and growth-promoting function of the IL-8 receptor beta in human
      melanoma cells.
AB  - The chemokine GRO alpha is an autocrine growth factor for melanoma cells.
      Although GRO alpha has been identified as a high affinity ligand for the IL-8
      receptor beta (IL-8R beta) in recombinant systems, the receptor mediating its
      action in melanoma cells has been a matter of debate. Here, we show by reverse
      transcription and PCR expression of IL-8R beta, mRNA transcripts in different
      melanoma cell lines and in normal human melanocytes. To characterize the role of
      the IL-8R beta in melanoma cells, antiserum was raised in rabbits against a
      fusion protein containing the NH2-terminal portion of the receptor. Its
      specificity was shown by flow cytometry with IL-8R beta-transfected HL60 cells. A
      specific epitope could be mapped with IL-8R beta mutants to the peptide sequence
      between ASP-4 and ASP-14 of this receptor. Binding studies with [125I]GRO alpha
      in IL-8R beta transfectants indicated ligand antagonistic properties of this Ab.
      Expression of IL-8R beta protein at the cell surface of various melanoma cell
      lines could be shown by flow cytometry with F(ab')2 fragments of the IL-8R beta
      antiserum. Moreover, anti-IL-8R beta Ab partially blocked specific binding of
      [125I]GRO alpha in various melanoma cell lines. Addition of F(ab')2 fragments of
      the IL-8R beta antiserum or of neutralizing anti-GRO alpha mAb to different
      melanoma cell lines identified this GRO alpha-IL-8R beta interaction as a major
      component required for serum-independent melanoma cell growth.

PMID- 8557990
TI  - An absolute and restricted requirement for IL-12 in natural killer cell IFN-gamma
      production and antiviral defense. Studies of natural killer and T cell responses
      in contrasting viral infections.
AB  - IL-12 is a potent induce of IFN-gamma and is associated with a wide variety of
      immunoregulatory activities. Using murine CMV (MCMV) and lymphocytic
      choriomeningitis virus (LCMV) models of acute viral infection, we show here that
      IL-12 is integrally involved in certain aspects of antiviral immunity.
      Experiments evaluating the production and function of IL-12 demonstrated the
      induction of biologically active factor early during Smith strain MCMV, but not
      Armstrong strain LCMV, infection. The MCMV-induced IL-12 was responsible for
      early NK cell IFN-gamma production and viral control, as in vivo IL-12
      neutralization by Ab treatment blocked both of these. In contrast, NK cell IFN
      gamma production could not be detected during LCMV infection, and IL-12
      neutralization had no effect on early LCMV replication. In both infections,
      treatments neutralizing IL-12 failed to alter either early NK cell cytotoxicity
      or later T cell responses, including IFN-gamma production and viral clearance on
      days 7 and 9 after infection. These data demonstrate the induction of IL-12
      production during certain viral infections and the function of IL-12 for
      eliciting NK cell IFN-gamma production and antiviral defense. Furthermore, they
      suggest the existence of IL-12-independent mechanisms for IFN-gamma induction and
      viral control by T cells.

PMID- 8557991
TI  - Macrophages have cell surface IL-10 that regulates macrophage bactericidal
      activity.
AB  - IL-10, which is secreted by multiple cell types, has regulatory effects on
      macrophages, including decreasing their ability to kill some microorganisms. The
      experiments presented here test the hypothesis that endogenous IL-10 inhibits the
      ability of macrophages to kill the facultative intracellular bacterium, Listeria
      monocytogenes. We show that the nonbactericidal macrophage hybrid, H36.12j (12j),
      can kill Listeria after incubation for 3 days with anti-IL-10 mAb. IL-10 was not
      detected in 12j macrophage supernatants by ELISA. However, flow cytometric
      analysis revealed high levels of IL-10 on the 12j cell surface. This indicates
      that macrophages that fail to secrete IL-10 may express IL-10 on the cell
      surface, and this IL-10 appears to suppress listericidal activity. Surface IL-10
      is not unique to the 12j macrophage hybrid and may correlate with the absence of
      bactericidal activity in other macrophages. For instance, nonlistericidal
      resident and thioglycolate-elicited peritoneal exudate cells have 24 to 72% IL-10
      positive macrophages. In contrast listericidal proteose peptone-elicited
      peritoneal exudate cells contained < 5% IL-10-positive macrophages. Whether this
      IL-10 is an integral membrane protein or is bound to IL-10 receptors is not yet
      known. However, the IL-10 does not elute with acid as other passively bound
      molecules do, nor does exogenous IL-10 bind to macrophages. In either case, since
      anti-IL-10 induces nonbactericidal macrophages to become bactericidal, the
      surface IL-10 is biologically active, and it appears to regulate macrophage
      bactericidal activity.

PMID- 8557992
TI  - Blood clearance kinetics and liver uptake of mononucleosomes in mice.
AB  - Nucleosomes generated by apoptosis have become of considerable interest in
      relation to pathogenesis of systemic lupus erythematosus in mice and humans.
      Therefore, the fate of circulating mononucleosomes was examined in normal
      C57Bl/6J mice. The mononucleosomes were prepared from chicken erythrocytes and
      radiolabeled on the histone component. The removal of nucleosomes from
      circulation at doses less than 11 micrograms of injected mononucleosomes was
      rapid, but with increasing doses of injected nucleosomes, the slopes of the
      removal curves decreased. Liver was the major organ for removal of circulating
      nucleosomes, accounting for 71.0 to 84.7% of nucleosomes removed from circulation
      at 10 min. After i.v. injection of nucleosomes, 0.52 +/- 0.15% localized in
      kidneys. With prior i.v. injection of histones, the glomerular localization of
      mononucleosomes increased threefold. The clearance of mononucleosomes was
      decreased sixfold by concurrent injection of ssDNA. These studies show that in
      mice, circulating mononucleosomes are handled similar to DNA, and they do not
      avidly localize in glomeruli unless histones have already bound to renal
      glomeruli.

PMID- 8557993
TI  - Bacterial lipopolysaccharide induces the association and coordinate activation of
      p53/56lyn and phosphatidylinositol 3-kinase in human monocytes.
AB  - p53/56lyn and other src family tyrosine kinases become activated in monocytes
      treated with LPS. In a variety of systems, phosphatidylinositol 3-kinase (PI 3
      kinase) is believed to be a downstream effector of tyrosine kinases, and
      activation of PI 3-kinase results in increased levels of D3-phosphorylated
      metabolites of phosphatidylinositol (PtdIns). To examine whether LPS activates PI
      3-kinase, freshly isolated human, peripheral blood monocytes were labeled in
      vitro with [32P]orthophosphate, and inositol phospholipids were detected after
      extraction and separation of lipids by TLC. Levels of PtdIns 3,4,5-trisphosphate
      (PtdIns 3,4,5-P3) were elevated within minutes of exposure of cells to LPS.
      Analysis of 32P-labeled lipid extracts of U937 cells by HPLC confirmed that
      levels of PtdIns 3,4,5-P3 increased rapidly following LPS treatment. Increased
      levels of PtdIns 3,4,5-P3 in LPS-treated cells resulted from an increase in the
      specific activity of PI 3-kinase. Thus, anti-PI 3-kinase immunoprecipitates
      prepared from unlabeled monocytes and assayed in an in vitro phosphorylation
      assay, using PtdIns as substrate, showed higher enzymatic activity when these
      were prepared from lysates of LPS-treated cells as compared with control cells.
      PI 3-kinase activity in immunoprecipitates was elevated as early as 2 min after
      LPS exposure and was dose dependent, with increased activity being observed at
      LPS concentrations as low as 10 pg/ml. Activation of PI 3-kinase involved
      signaling through the monocyte cell surface molecule CD14, since pretreatment of
      cells with Abs to CD14 abrogated LPS-induced increases in PtdIns 3,4,5-P3.
      Immunoprecipitates of p53/56lyn from LPS-treated cells showed a time-dependent
      and transient increase in PI 3-kinase activity assayed in vitro, coordinate with
      activation of p53/56lyn, indicating that LPS induces the association and
      simultaneous activation of these two enzymes in vivo. These findings indicate
      that monocytes respond to LPS with the rapid activation of PI 3-kinase, resulting
      in transient increases in levels of PtdIns 3,4,5-P3. This process is CD14
      dependent and involves the physical association of PI 3-kinase with activated
      p53/56lyn.

PMID- 8557995
TI  - Extracellular matrix proteins attenuate activation and degranulation of
      stimulated eosinophils.
AB  - Cellular adhesion plays an important role in the recruitment and activation of
      eosinophils. Here, we investigated whether extracellular matrix (ECM) proteins
      modify effector functions of activated human eosinophils. We coated 96-well
      plates with laminin or fibronectin and blocked nonspecific protein-binding sites
      with human serum albumin (HSA). When eosinophils were stimulated with platelet
      activating factor (PAF) and incubated in these ECM-coated wells, the eosinophils
      adhered using both beta 1- and beta 2-integrins. Degranulation of eosinophils
      adherent to laminin- and fibronectin-coated wells was reduced about 50% compared
      with cells adherent to uncoated, HSA-blocked wells. Furthermore, these inhibitory
      effects of laminin and fibronectin were concentration-dependent and secretagogue
      specific, that is, degranulation induced by C5a and IL-5 was inhibited while
      degranulation induced by secretory IgA and PMA was not inhibited. Plasma
      fibronectin, type I collagen and type IV collagen also inhibited PAF- and C5a
      induced eosinophil degranulation, whereas fibrinogen did not. By microscopy, PAF
      stimulated eosinophils, adhering to uncoated HSA-blocked wells, appeared
      elongated with many pseudopods. In contrast, eosinophils adhering to laminin
      coated wells appeared oval with few pseudopods. Furthermore, when cells were
      incubated in laminin-coated wells, PAF-stimulated production of a second
      messenger, inositol phosphate, was markedly reduced. These findings suggest that
      ECM protein, such as laminin and fibronectin, attenuate both activation and
      degranulation of eosinophils and also influence their morphology after
      stimulation by physiologic secretagogues. Thus, ECM proteins may regulate
      activation of eosinophils, as they traverse between the peripheral blood and
      their targets.

PMID- 8557994
TI  - A20 zinc finger protein inhibits TNF and IL-1 signaling.
AB  - A20 zinc finger protein is a product of a cytokine-induced primary response gene.
      In this report, we demonstrate that A20 specifically inhibits signal transduction
      pathways induced by TNF and IL-1, suggesting that it functions as a negative
      regulator of the cytokine response. Overexpression of A20 in MCF7 breast
      carcinoma cells or in WEHI-S fibrosarcoma cells inhibits apoptosis induced by
      TNF, whereas cytotoxicity induced by anti-Fas (anti-CD95); lymphokine-activated
      killer (LAK) cells, serum starvation, oxidative stress, or okadaic acid is not
      inhibited. Overexpression of A20 also inhibits TNF-induced activation of
      phospholipase A2 in a similar dose-dependent manner as it inhibits TNF-mediated
      apoptosis, whereas it does not affect the activation of phospholipase A2 by anti
      Fas. Interestingly, A20 also blocks TNF-induced signal transduction pathways not
      directly related to the cytotoxicity, namely activation of NF-kappa B and AP-1
      transcription factors. Activation of these transcription factors by a
      functionally related cytokine, IL-1, is also inhibited by A20, whereas activation
      induced by hydrogen peroxide or phorbol ester is unaffected. Overexpression of
      A20 does not affect the binding of TNF to its cell surface receptors. These data
      suggest that A20 functions as a negative regulator of TNF and IL-1, interfering
      with signal transduction pathways at an early point following receptor binding
      but before the activation of various second messengers, leading to the wide
      variety of effects induced by these cytokines.

PMID- 8557996
TI  - Local inflammation caused by a monoclonal antibody that blocks the function of
      the rat membrane inhibitor of C3 convertase.
AB  - The participation of membrane inhibitors in C-mediated inflammation in vivo was
      analyzed in rats with the use of mAbs against membrane inhibitors of C. 512Ag
      inhibits C3 convertase of homologous rat C and rat CD59 prevents the formation of
      homologous membrane attack complexes. The histologic distributions of 512Ag and
      CD59 in rat skin were essentially the same. However, although intracutaneous
      administration of mAb against 512Ag (anti-512Ag) in the form of F(ab')2 induced a
      remarkable inflammatory response visualized by exudation of Evans blue that had
      been previously injected i.v., the mAb against CD59 caused no inflammatory
      exudate. Furthermore, anti-512Ag F(ab')2 caused deposition of C3 followed by
      intense polymorphonuclear leukocyte infiltration and hemorrhage at the injection
      sites within 24 h. This reaction was completely abrogated by depletion of C.
      Therefore, spontaneous C activation on self cell membranes requires amplification
      at the C3 convertase step, which is restricted by membrane inhibitors such as
      512Ag, thus preventing inflammation. A type II allergic response might
      preferentially occur at sites that exhibit an impairment of membrane inhibitor(s)
      of C3 convertase. However, although depletion of leukocytes by preadministration
      of cyclophosphamide did not reduce C3 deposition by anti-512Ag. Evans blue
      exudation was appreciably reduced, indicating that infiltrated leukocytes play a
      role in enhancing and prolonging inflammation initiated by local C activation.

PMID- 8557997
TI  - Serum amyloid A binds specific extracellular matrix glycoproteins and induces the
      adhesion of resting CD4+ T cells.
AB  - Serum amyloid A (SAA), a prototypic acute phase protein reactant, exists
      naturally in the serum of healthy individuals. However, the levels of SAA in
      serum and its presence in sites of inflammation increase during certain chronic
      diseases associated with a local elevation of cytokine concentrations. Although
      the chemical structure of SAA is defined, its putative immunologic role(s) is
      still obscure. Nevertheless, it has been shown that 1) SAA acts as a
      chemoattractant and regulator of the migration of monocytes, polymorphonuclear
      cells, and T lymphocytes through endothelial cell monolayers; and 2) SAA and its
      proteolytically degraded N-terminal amyloid A fragment contain an extracellular
      matrix (ECM)-related cell adhesion epitopes. Herein, we examined whether SAA can
      associate with specific ECM moieties, and whether immobilized SAA-ECM complexes
      affect T lymphocyte adhesion. Radiolabeled human rSAA ([125I]rSAA) interacted
      avidly (Kd = 10(-9) M) and transiently with intact ECM, laminin, and vitronectin,
      but not with fibronectin or collagen type II. The binding of [125I]rSAA to ECM
      and laminin was inhibited by unlabeled rSAA and by the AA fragment, but not by
      the C-terminal portion of SAA (amino acid residues 2-82 and 77-104,
      respectively). Upon interactions with SAA or amyloid A, immobilized ECM, laminin,
      and vitronectin induced the adhesion of resting human CD4+ T cells in an
      apparently beta 1-integrin-mediated manner. Thus, the ECM appears to serve as a
      temporary anchorage site for SAA and amyloid A, and these ECM-complexed molecules
      seem to be involved in regulating the recruitment and accumulation of immunocytes
      in extravascular inflammatory compartments.

PMID- 8557998
TI  - Regulation of murine macrophage IL-12 production. Activation of macrophages in
      vivo, restimulation in vitro, and modulation by other cytokines.
AB  - IL-12 is important in the host response to a variety of pathogens. It plays an
      adjuvant-like role in an initial immune response as well as a therapeutic role in
      established infections. Despite its well documented importance, comparatively
      little is known about the regulation of IL-12 production. In this study, we
      examined IL-12 production by cultured murine peritoneal macrophages from two
      perspectives: 1) macrophage activation in vivo, and 2) stimulation of IL-12
      secretion in vitro. Macrophages were maximally activated within 48 h in vivo
      during infection with Listeria. Interestingly, although avirulent or heat-killed
      Listeria induced only minimal production of IL-12 by macrophages, the immunogenic
      combination of heat-killed bacteria and rIL-12 was highly stimulatory for IL-12
      production. LPS and peritoneal inflammatory agents were also stimulatory, but
      latex beads were ineffective, indicating that microbial components were essential
      and phagocytosis alone was insufficient. Restimulation in vitro revealed similar
      patterns, in that infection and LPS were stimulatory but latex beads were not. A
      systematic survey of potential stimulatory agents showed that microbial heat
      shock proteins, crude bacterial extracts, bacterial superantigens, a yeast
      extract, and dsRNA induced IL-12 in vitro. Other cytokines also influenced IL-12
      induction. IFN-gamma, which is up-regulated during infection, acted in synergy
      with other stimuli, suggesting an amplification loop for IL-12 production,
      whereas IL-4, IL-10, IL-13, and TGF-beta were inhibitory. The existence of a
      broad range of stimuli from a wide variety of pathogenic organisms underscores
      the fundamental importance of IL-12 in host defense.

PMID- 8557999
TI  - Regulation of bioactive IL-12 production in lipopolysaccharide-stimulated human
      monocytes is determined by the expression of the p35 subunit.
AB  - IL-12 enhances IFN-gamma production by NK cells and T lymphocytes and plays a
      pivotal role in the development of Th1 cells. Bioactive IL-12 (p70) is composed
      of two subunits, p35, which is only secreted as part of the p70 dimer, and p40,
      which can also be secreted by itself. The IL-12 subunits are encoded by two
      separate genes. Therefore, we studied to what extent the expression of each of
      the subunits contributes to the regulation of IL-12 production. We found that in
      LPS-stimulated whole blood and purified monocytes, p70 and p40 production are
      enhanced by IFN-gamma and inhibited by IL-10 and IL-4. However, IFN-gamma and IL
      10 had stronger effects on p70 production than on p40 production, and IL-4
      affected p40 production more strongly. Concomitantly, in all experimental
      conditions tested, p40 production greatly exceeded p70 production, suggesting
      that p35 expression was limiting. Analysis of p35 and p40 mRNA expression by PCR
      confirmed this notion. Resting purified monocytes expressed neither p40 nor p35
      mRNA. The effects of IFN-gamma, IL-10, and IL-4 on the p35 mRNA expression in LPS
      stimulated purified monocytes were similar to the effects of these cytokines on
      p70 protein production, and the p40 mRNA expression corresponded to p40 protein
      production. Our results imply that production of the two IL-12 subunits is
      differently regulated for each subunit, mainly at the level of mRNA expression,
      and that the level of bioactive IL-12 production in monocytes in response to LPS
      and cytokines is determined by the level of p35 expression.

PMID- 8558000
TI  - The role of nitric oxide in proteoglycan turnover by bovine articular cartilage
      organ cultures.
AB  - Monolayer cultures of articular chondrocytes synthesize large amounts of nitric
      oxide (NO) following exposure to IL-1. The latter has antianabolic and
      procatabolic activities on these cells, but little is known about the role, if
      any, of NO in the integrated metabolic pathways of the chondrocyte. In the
      present study, the role of endogenously produced NO in both the synthesis and
      degradation of proteoglycans was investigated for the first time. Bovine
      articular cartilage slices exposed to 20 U/ml human rIL-1 beta (hrIL-1 beta)
      synthesized large amounts of NO for 1 to 2 days, after which production fell to a
      steady state level approximately 20% of the peak value for the remainder of the
      14-day incubation. The NO synthase inhibitor, N-monomethyl L-arginine (L-NMA, 1
      mM), blocked NO production and enhanced the acute catabolic effects of hrIL-1
      beta in cartilage derived from both cartilage derived from both calves and adult
      animals. However, in late cultures, release of proteoglycans was reduced in the
      presence of L-NMA. The proteolytic activity in conditioned medium of these
      cultures (measured as caseinolytic activity) was enhanced by L-NMA; however, this
      inhibitor did not affect the rates of synthesis of proteoglycans. Although NO is
      widely assumed to be a mediator of cartilage catabolism, our data suggest that it
      may instead have an acute protective effect. Whether this effect is maintained
      chronically is less clear.

PMID- 8558001
TI  - Vascular endothelial platelet endothelial adhesion molecule-1 (PECAM-1)
      expression is decreased by TNF-alpha and IFN-gamma. Evidence for cytokine-induced
      destabilization of messenger ribonucleic acid transcripts in bovine endothelial
      cells.
AB  - Platelet endothelial cell-adhesion molecule-1 (PECAM-1, CD31) is constitutively
      expressed by vascular endothelium and concentrates at intercellular junctions.
      Regulation of PECAM-1 expression on endothelial cells may modulate leukocyte
      trafficking, angiogenesis, and vascular permeability. Given that cytokine
      activation induces profound alterations in endothelial phenotype, studies sought
      to determine whether cytokine treatment modulated PECAM-1 mRNA and protein
      content in macro- and microvascular endothelial cells. Northern blot analysis
      revealed expression of PECAM-1 mRNA transcripts in endothelial cells derived from
      bovine aorta, bovine glomeruli, and human umbilical vein under basal conditions.
      Treatment of endothelial cells with TNF-alpha and/or IFN-gamma led to dramatic
      decreases in steady-state levels of PECAM-1 mRNA transcripts. In contrast,
      reciprocal induction of ICAM-1 mRNA was evident. Actinomycin D chase experiments
      demonstrated that cytokines selectively destabilize PECAM-1 mRNA transcripts in
      bovine endothelial cells, decreasing the PECAM-1 mRNA transcript t1/2 from basal
      values of 15 +/- 2 h to 4 +/- 1 h in TNF-alpha- and IFN-gamma-treated cells (p <
      0.005), an effect that appeared to be independent of new protein synthesis.
      Nuclear run-off analysis demonstrated no change in the rates of PECAM-1 gene
      transcription in response to cytokines treatment. Immunoblots and quantitative
      indirect immunofluorescence indicated decreased total cellular and cell-surface
      PECAM-1 protein expression following cytokine treatment. These findings provide
      evidence for cytokine-induced reciprocal regulation of transcripts of Ig-like
      adhesion molecules on vascular endothelium.

PMID- 8558002
TI  - Augmentation by calmodulin of ADP-ribosylation factor-stimulated phospholipase D
      activity in permeabilized rabbit peritoneal neutrophils.
AB  - Activation of the membrane-bound phospholipase D (PLD) requires cytosolic
      factor(s), and ADP-ribosylation factor (ARF) has been identified as a cytosolic
      PLD activator. In the present study, we demonstrate that calmodulin (CaM) and ARF
      are both involved in PLD activation in rabbit peritoneal neutrophils. The PLD
      activity of streptolysin O-permeabilized, cytosol-depleted rabbit neutrophils was
      significantly enhanced when the permeabilized cells were reconstituted with
      bovine brain cytosol in the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP
      gamma S), whereas there was little activation of the enzyme in the absence of
      cytosol. The GTP gamma S-stimulated PLD activity in the presence of cytosol was
      augmented on increasing the concentration of free Ca2+. The PLD activity
      stimulated by GTP gamma S and Ca2+ in this system was inhibited by the calmodulin
      inhibitor W-7. These findings suggest that CaM plays a role as a cytosolic PLD
      activator. Moreover, highly purified CaM alone, as well as partially purified ARF
      alone, promoted a slight stimulation of the PLD activity in permeabilized
      neutrophils. Interestingly, ARF-stimulated PLD activity was augmented by CaM in
      the presence of GTP gamma S and Ca2+. This augmentation was again inhibited by W
      7, as well as by the structurally unrelated CaM inhibitor trifluoperazine. These
      data imply that CaM stimulates the PLD activity of rabbit neutrophils in concert
      with ARF.

PMID- 8558003
TI  - Analysis of the sugar specificity and molecular location of the beta-glucan
      binding lectin site of complement receptor type 3 (CD11b/CD18).
AB  - Zymosan, the cell wall from Saccharomyces cerevisiae, was reported to be a
      macrophage activator through its beta-glucan over 30 yr ago. Nevertheless, the
      identity of the beta-glucan receptor has been controversial. This study showed
      that the alpha M beta 2-integrin, CR3 (Mac-1, CD11b/CD18) served as the beta
      glucan receptor through one or more lectin sites located outside of the CD11b I
      domain that contains the binding sites for iC3b, ICAM-1, and fibrinogen. Sugar
      specificity, analyzed with FITC-labeled soluble polysaccharides and flow
      cytometry, showed CR3-specific staining with several pure beta-glucans but not
      with alpha-mannan. However, a 10-kDa soluble zymosan polysaccharide (SZP) with
      high affinity (6.7 x 10(-8) M) for CR3 consisted largely of mannose and
      approximately 5% glucose. Binding of either SZP-FITC or beta-glucan-FITC to CR3
      was blocked not only by pure beta-glucans from yeast, mushroom, seaweed, or
      barley, but also by N-acetyl-D-glucosamine (NADG), alpha- or beta
      methylmannoside, and alpha- or beta-methyl-glucoside. SZP-FITC and beta-glucan
      FITC stained all leukocyte types similarly to anti-CR3-FITC, and polysaccharide
      FITC staining was inhibited > or = 95% by unlabeled anti-CR3. SZP-FITC staining
      of cells expressing recombinant chimeras between CR3 and CR4 (p150,95,
      CD11c/CD18) suggested that both the divalent cation-binding region of CD11b and
      the region C-terminal to it may regulate binding of polysaccharides to CR3.
      Unlabeled SZP or beta-glucan also blocked CR3 staining by 11 mAb to C-terminal
      domain epitopes of CD11b but had no effect on staining by mAb directed to the I
      domain. In conclusion, CR3 serves as the leukocyte beta-glucan receptor through a
      cation-independent lectin site located C-terminal to the I-domain of CD11b. Its
      sugar specificity is broader than originally appreciated, allowing it to react
      with certain polysaccharides containing mannose or NADG, as well as glucose.

PMID- 8558004
TI  - Phosphorylation of MRP14, an S100 protein expressed during monocytic
      differentiation, modulates Ca(2+)-dependent translocation from cytoplasm to
      membranes and cytoskeleton.
AB  - MRP8 and MRP14 are two Ca(2+)-binding proteins expressed in myelomonocytic cells.
      Complexes of MRP8 and MRP14 colocalize with membranes and intermediate filaments
      in a Ca(2+)-dependent manner. MRP14, unlike MRP8, exists in two isoforms, the
      smaller of which (MRP14') has been shown to lack the first four amino acids; both
      MRP14 and MRP14' are also present as phosphorylated forms. As shown in the
      present work by metabolic labeling of monocytes with [35S]methionine, MRP14 and
      MRP14' are translated simultaneously. By PCR analysis we found no evidence for
      the presence of different mRNA species. Since MRP14 is encoded by a single copy
      gene, our data indicate that MRP14' formation is due to alternative translation
      of a single mRNA species. Two-dimensional electrophoresis of [32P]orthophosphate
      labeled monocyte proteins followed by Western blotting and autoradiography
      revealed that the two phosphorylated MRP14 isoforms incorporated the bulk of the
      radioactivity found in monocytic proteins. Using differential centrifugation we
      demonstrated the presence of distinct isoform patterns in different subcellular
      locations. Further, in response to elevated Ca2+ concentrations we observed a
      preferential translocation of phosphorylated MRP14 isoforms from the cytosol
      toward membranes and the cytoskeleton. This might be caused by altered calcium
      binding, and indeed, using isoelectric focusing and 45Ca2+ overlay the MRP14 band
      containing phosphorylated MRP14 revealed increased Ca2+ binding compared with
      bands containing other MRP14 isoforms. This represents the first evidence for
      functional differences in phosphorylated MRP14 isoforms compared with
      nonphosphorylated MRP14 isoforms. These functional differences suggest that MRP14
      represents the regulatory subunit of MRP8/MRP14 complexes.

PMID- 8558005
TI  - Study of complement-mediated anaphylaxis in humans. The role of IgG subclasses
      (IgG1 and/or IgG4) in the complement-activating capacity of immune complexes.
AB  - The role of Ig classes and subclasses in complement activation has been
      investigated both in vitro and in experimental animals, but not in humans. This
      study was conducted to determine the immunologic events of post-transfusion
      anaphylaxis in humans, and the effects of immune complexes of different IgG
      subclass compositions on complement activation. The ability of immune complexes
      containing mixed IgG1 and IgG4 or IgG4 Ab only to activate complement was
      investigated in two patients with von Willebrand's disease (a congenital bleeding
      disorder). This disease was complicated by precipitating IgG alloantibodies to
      von Willebrand factor (vWF), which triggered complement-mediated anaphylaxis
      after infusion of vWF-containing preparations. Complement activation was greater
      in the presence of mixed IgG1- and IgG4-vWF complexes than with IgG4-vWF alone.
      In one patient, the generation of large amounts of C4a, C3a, and terminal
      complement complexes following the formation of mixed IgG1- and IgG4-vWF was
      associated with life-threatening anaphylaxis. In this patient, IgG4 appeared to
      have no inhibitory effect on antigen-bound IgG1-mediated complement activation.
      In the other patient, formation of IgG4-vWF led to a lesser degree of complement
      activation and was associated with moderately severe anaphylaxis. Since neither
      patient showed any biochemical alterations indicating the involvement of mast
      cells or the contact phase of coagulation at any time, it is probable that the
      pathogenetic mechanism of the clinical syndrome was a direct effect of complement
      anaphylatoxins on vascular permeability and smooth muscle contraction. In both
      patients, IgG-vWF bound C4 and C3 (IgG4-vWF to a lesser extent than mixed IgG1-
      and IgG4-vWF), and this probably prevented serum sickness as a complication.

PMID- 8558006
TI  - Intervention of CD4+ cell subset shifts and autoimmunity in the BXSB mouse by
      murine CTLA4Ig.
AB  - In the BXSB autoimmune disease-prone mouse strain, male mice develop severe lupus
      like symptoms and die early in life (4-6 mo), whereas females do not. We have
      previously demonstrated that profound phenotypic and functional changes occur
      with age in CD4+ cells from BXSB males. CD4+ cells from males (4 mo old) were
      predominantly CD44high, CD45RBlow, and MEL-14low (activated/memory phenotypes),
      while the reciprocal phenotypes characteristic of naive cells were prevalent in
      age-matched females and young adult males (2 mo old). CD4+ cells from older males
      proliferated less and produced less IL-2 and IFN-gamma than cells from either
      females or young males in response to immobilized anti-CD3 mAb. We tested the
      effect of CTLA4Ig treatment on the progression of disease in BXSB males. CD4+
      cells from CTLA4Ig-treated mice at 4 mo of age were predominantly CD44low,
      CD45RBhigh, and MEL-14high phenotypes that were identical with those observed in
      CD4+ cells from young (3-mo-old) females. In contrast, control male mice treated
      with IgG2a accumulated the CD4+ memory phenotype. CD4+ cells from 4-mo-old male
      CTLA4Ig-treated mice proliferated and produced IL-2 at levels similar to those of
      cells from females in response to immobilized anti-CD3 mAb. Furthermore, in
      contrast to IgG2a-treated mice, female and CTLA4Ig-treated male mice at 4 mo of
      age produced no anti-chromatin Abs. Three of four male mice injected with CTLA4Ig
      until 6 mo of age appeared healthy at 8 mo of age, whereas all five of IgG2a
      treated control males died by 6 mo of age. These 8-mo-old CTLA4Ig-treated males
      showed variable resistance to autoimmunity as well as function and phenotype
      marker expression, and a less striking glomerulonephritis than 4-mo-old untreated
      males. The results of this study demonstrate that the rampant T cell activation
      and T cell dysfunction that occur in male BXSB mice by 4 mo of age are abrogated
      by blocking the CTLA4-dependent costimulatory signal(s). They also show that
      treatment with CTLA4Ig can suppress the pathogenesis of disease and increase
      longevity.

PMID- 8558007
TI  - Abnormal thymocyte subset distribution and differential reduction of CD4+ and
      CD8+ T cell subsets during peripheral maturation in diabetes-prone BioBreeding
      rats.
AB  - In this study we quantified CD8+ and CD4+ T cells in T lymphocytopenic BB rats as
      compared with control rats at given stages along the maturational pathway from
      immature thymocytes to mature peripheral T cells. Our results show that BB rats
      exhibit abnormal thymocyte subset distribution. Numbers of mature TCRhigh/CD4-8+
      thymocytes, and also their TCRhigh/CD4+8+ precursors were decreased, as were
      levels of CD8 expression on all thymocyte subsets investigated. By analogy with
      mouse thymocyte development, these findings suggest a decreased efficiency for
      positive selection of CD8 precursors in BB rats. Furthermore, as related to the
      number of available mature TCRhigh single positive thymocytes, numbers of CD4+
      and CD8+ T cells most recently migrated from the thymus were severely decreased
      in BB blood, indicating either reduced thymic output or rapid cell death after
      migration. Subsequently, in peripheral blood and cervical lymph nodes, a 95%
      decrease of CD8+ and a 50 to 80% decrease of CD4+ T cells were demonstrated upon
      maturation from recent thymic migrants to mature peripheral T cells, leaving the
      BB rat with a severely reduced T cell population, consisting of CD4+ T cells and
      a minute population of CD8+ T cells. The vast majority of the latter was found to
      have an immature peripheral phenotype. Possible consequences of our findings for
      the generation of autoreactive CD8+ T cells are discussed.

PMID- 8558008
TI  - Adoptively transferred CD8+ T lymphocytes provide protection against TMEV-induced
      demyelinating disease in BALB/c mice.
AB  - On intracerebral infection with the BeAn strain of Theiler's murine
      encephalomyelitis virus (TMEV), certain mouse strains develop a chronic
      demyelinating disease similar both clinically and pathologically to human
      multiple sclerosis. Other strains remain resistant. We previously established
      that differential susceptibility to this demyelinating disease exists among
      BALB/c substrains, with BALB/cAnNCr mice being susceptible while BALB/cByJ mice
      are resistant. BALB/cByJ mice are rendered susceptible to TMEV-induced
      demyelination on exposure to low dose gamma-irradiation before TMEV infection.
      BALB/cAnNCr and irradiated, infected BALB/cByJ animals are protected against TMEV
      induced demyelination by the transfer of a splenic population from TMEV-infected
      BALB/cByJ donors. Resistance to demyelination appears to be mediated by a CD8+
      radiosensitive population, which is induced on infection with TMEV and which must
      act early to establish resistance to TMEV-induced demyelination.

PMID- 8558009
TI  - Mechanisms for the transendothelial migration of HIV-1-infected monocytes into
      brain.
AB  - HIV-1 penetration of the brain is a pivotal event in the neuropathogenesis of
      AIDS-associated dementia. The establishment of productive viral replication or up
      regulation of adhesion molecule expression on brain microvascular endothelial
      cells (BMVEC) could permit entry of HIV into the central nervous system. To
      investigate the contribution of both, we inoculated primary human BMVEC with high
      titer macrophage-tropic HIV-1 or cocultured them with virus-infected monocytes.
      In both instances, BMVEC failed to demonstrate productive viral replication. Cell
      to cell contact between monocytes and microvascular endothelium resulted in E
      selectin expression on BMVEC. BMVEC. cocultured with LPS-activated HIV-infected
      monocytes expressed even higher levels of E-selectin and vascular cell adhesion
      molecule-1 (VCAM-1). Transwell assays supported a role of soluble factors, from
      virus-infected monocytes, for the induction of adhesion molecules on BMVEC. To
      verify the in vivo relevance of these findings, levels of adhesion molecules were
      compared with those of proinflammatory cytokines and HIV-1 gene products in brain
      tissue of AIDS patients with or without encephalitis and HIV-seronegative
      controls. E-Selectin, and to a lesser degree VCAM-1, paralleled the levels of HIV
      1 gene products and proinflammatory cytokines in brain tissue of subjects with
      encephalitis. Most importantly, an association between macrophage infiltration
      and increased endothelial cell adhesion molecules was observed in encephalitic
      brains. Monocyte binding to encephalitic brain tissue was blocked with Abs to
      VCAM-1 and E-selectin. These data, taken together, suggest that HIV entry into
      brain is, in part, a consequence of the ability of virus-infected and immune
      activated monocytes to induce adhesion molecules on brain endothelium.

PMID- 8558010
TI  - Both Sm and DNA are selecting antigens in the anti-Sm B cell response in
      autoimmune MRL/lpr mice.
AB  - More than half of the anti-Sm hybridomas isolated from MRL/Mp-lpr/lpr (MRL/lpr)
      mice produce Abs that also bind ssDNA, and half of these bind dsDNA. Intraclonal
      comparisons indicate that DNA is a selecting Ag for at least some dual-binding
      clones. To determine whether Sm itself is a selecting Ag for anti-Sm, we have
      identified the somatic mutations within the expressed VH and V kappa genes of
      eight anti-Sm hybridomas, six of which do not bind DNA. We find these V genes
      have between 0 and 12 somatic mutations each, and that four hybridomas possess a
      higher number of heavy or light chain CDR replacement (R) mutations than expected
      by chance, suggesting that these anti-Sm-producing B cells have undergone Ag
      selection. To demonstrate directly the effect of somatic mutation on Sm binding,
      we have engineered the unmutated counterpart of Ab 2-12, an Sm-specific hybridoma
      Ab with a nonrandom distribution of V kappa CDR R mutations, and compared its
      ability to bind Sm and ssDNA with that of the originally isolated 2-12 Ab. We
      find that the unmutated Ab has a much lower avidity for Sm than the mutant, but,
      unlike the mutant, it binds ssDNA. We conclude that Sm can drive clonal expansion
      in the anti-Sm response, and that Sm-only binding B cells can arise from Sm/DNA
      dual-binding B cell clonal precursors. These data also suggest that dual binding
      is not necessary to sustain clonal expansion. Thus, this response is unique in
      that it can be driven by either of two Ags.

PMID- 8558011
TI  - HIV glycoprotein 120 enhances intercellular adhesion molecule-1 gene expression
      in glial cells. Involvement of Janus kinase/signal transducer and activator of
      transcription and protein kinase C signaling pathways.
AB  - It is well established that the two major glial cells in the central nervous
      system (CNS), astrocytes and microglia, are key participants in mediating the
      neurologic dysfunction associated with HIV infection of the CNS. In this study,
      we investigated the ability of the major envelope glycoprotein of HIV,
      glycoprotein 120 (gp120), to regulate intercellular adhesion molecule-1 (ICAM-1)
      expression in glial cells, because ICAM-1 is important in mediating immune
      responsiveness in the CNS, facilitating entry of HIV-infected cells into the CNS,
      and promoting syncytia formation. Our results indicate that gp120 enhances ICAM-1
      gene expression in primary rat astrocytes, primary human astrocytes, a human
      astroglioma cell line CRT, and primary rat microglia. The signal transduction
      events involved in gp120-mediated enhancement of ICAM-1 appear to involve
      activation of both protein kinase C and tyrosine kinase, because inhibitors of
      protein kinase C and tyrosine kinase abrogate gp120-mediated ICAM-1 expression in
      both astrocytes and microglia. Moreover, gp120 induces tyrosine phosphorylation
      of signal transducer and activator of transcription (STAT-1 alpha) as well as the
      Janus kinase (JAK2) in glial cells. We also demonstrate that gp120-mediated ICAM
      1 expression has functional significance, as it enhances the ability of monocytic
      cells to bind to gp120-stimulated human astrocytes in an ICAM-1/beta 2 integrin
      dependent fashion. These results provide new insights into how gp120 can
      influence the involvement of glial cells in the pathogenesis of AIDS dementia
      complex.

PMID- 8558012
TI  - Cytokine gene expression in islets and thyroids of BB rats. IFN-gamma and IL
      12p40 mRNA increase with age in both diabetic and insulin-treated nondiabetic BB
      rats.
AB  - Inflammatory cytokines, particularly those produced by Th1 type lymphocytes, are
      hypothesized to play a major role in the pathogenesis of autoimmune diseases. The
      present studies investigated this hypothesis in the BB rat. Diabetes-prone (DP)
      BB rats develop spontaneous hyperglycemia and thyroiditis. Coisogenic diabetes
      resistant (DR) BB rats do not develop either disorder spontaneously, but both
      diseases are induced by depletion of RT6+ T cells. Reverse transcriptase-PCR was
      used to measure mRNA encoding type 1 and type 2 cytokines. In both DP and RT6
      depleted DR rats, IFN-gamma mRNA was present in islets before and during disease
      onset. IL-2 and IL-4 mRNAs were minimal or undetectable in infiltrated islets but
      present in activated peripheral T cells. IL-10 mRNA was present at low abundance
      in infiltrating T cells. These observations suggested a Th1 type inflammatory
      response, and consistent with this interpretation, we observed that mRNA encoding
      the p40 chain of IL-12 was also present before and during disease onset. Similar
      cytokine mRNA profiles were observed in the thyroids of RT6-depleted DR rats and
      in the islets of DP rats treated with prophylactic parenteral insulin to prevent
      diabetes. We conclude that IFN-gamma and IL-12 may play a major role in the
      expression of insulitis and thyroiditis in the BB rat, that Th1 lymphocytes may
      predominate over Th2 lymphocytes in these inflammatory lesions, and that
      prevention of diabetes by insulin is not associated with an alteration in the
      cytokine gene profile of islet infiltrating cells.

PMID- 8558013
TI  - CD28-mediated up-regulation of beta 1-integrin adhesion involves
      phosphatidylinositol 3-kinase.
AB  - Cross-linking of the CD28 Ag on T cells results in increased beta 1-integrin
      mediated adhesion to fibronectin. Chimeric contructs containing the CD28
      cytoplasmic domain fused to the extracellular and transmembrane regions of CD2
      were expressed in HL60 cells to investigate CD28-mediated regulation of adhesion.
      Ab cross-linking of the CD2/28 chimera resulted in increased beta 1-dependent
      adhesion of HL60 transfectants to fibronectin. Induced binding was completely
      inhibited by the phosphatidylinositol 3-kinase (PI 3-K) inhibitor wortmannin.
      Cross-linking of the CD2/28 chimera also induced association of the p85 subunit
      of PI 3-K with the CD2/28 cytoplasmic domain. In contrast, cross-linking of a
      CD2/28 chimera containing a tyrosine to phenylalanine substitution in the YMNM
      motif did not result in increased adhesion to fibronectin and did not lead to
      association of the chimera with PI 3-K. These results directly implicate the YMNM
      motif and PI 3-K in the regulation of beta 1-integrin activity by the CD28 Ag.

PMID- 8558014
TI  - IL-12, as an adjuvant, promotes a T helper 1 cell, but does not suppress a T
      helper 2 cell recall response.
AB  - IL-12 is a potent inducer of NK and cytolytic T cell activity, IFN-gamma
      production, and T cell proliferation, and is necessary for differentiation of
      naive T cells to the Th1 subset. We have previously shown that IL-12 promotes a
      primary Th1 response and suppresses a primary Th2 response in lymph nodes of mice
      primed with a model hapten-protein conjugate, 2,4,6-trinitrophenyl (TNP)-keyhole
      limpet hemocyanin (KLH). We have now extended these studies to determine the Th
      phenotype of the recall response following immunization with soluble Ag and IL
      12. For these experiments, mice were primed with TNP-KLH with or without
      treatment with IL-12, allowed to progress beyond the primary immune response, and
      challenged by i.p. injection of TNP-KLH. The phenotype of the recall response was
      monitored by measuring ex vivo production of IFN-gamma and IL-4 in Ag-stimulated
      lymph node and spleen cell cultures. Titer and isotype of TNP-specific serum Abs
      were also evaluated. Mice primed with Ag+IL-12 developed a Th1 recall response,
      as detected by KLH-specific IFN-gamma production from cultured spleen cells and
      the presence of TNP-specific IgG2a Ab in serum. However, they also developed an
      Ag-specific Th2 recall response, as characterized by Ag-induced IL-4 production
      from spleen cells and the presence of high titers of anti-TNP IgG1 in the serum.
      Studies of the cytokine profile during the primary response revealed that IL-12
      induced in spleen cells the capacity to express both IL-4 and IFN-gamma. CD4+ T
      cells are necessary for production of IL-4 in the spleens of IL-12-treated mice,
      and most likely account for the Th2 recall response detected in mice primed with
      Ag+IL-12. These results indicate that the Th1 phenotype induced by immunization
      with IL-12 and Ag is maintained so that a Th1 recall response is expressed upon
      subsequent challenge with Ag. However, immunization with IL-12 also supports the
      development of a Th2 recall response, indicating that the Th1-inducing effect of
      IL-12 in vivo is not accompanied by a long lasting suppression of Th2
      development.

PMID- 8558015
TI  - Human T cell repertoire generation in the absence of MHC class II expression
      results in a circulating CD4+CD8- population with altered physicochemical
      properties of complementarity-determining region 3.
AB  - In this study, we have investigated the impact of deficient MHC class II
      expression on the use of TCRBV6 and TCRBJ gene elements, and on the pattern of
      amino acid incorporation exhibited in the N1-D-N2 segments of the third
      complementarity-determining region (CDR3) of these TCRBV6 rearrangements. To this
      end, we have analyzed circulating T cells from three, nonrelated MHC class II
      deficient (bare lymphocyte syndrome (BLS)) patients and three MHC class II
      expressing family members. The patients and healthy controls exhibited similar,
      nonrandom usage profiles of TCRBV6 and TCRBJ gene elements in both the CD4+CD8-
      and the CD4-CD8+ subsets of peripheral blood T cells. No statistically
      significant differences between patients and controls were detected in the length
      of CDR3, or in the amount of non-germline modification at the sites of
      recombination. However, detailed analysis of the TCRBV6 rearrangements derived
      from the CD4+CD8- subsets from the BLS patients revealed patterns of amino acid
      incorporation into the N1-D-N2 region of CDR3 that resulted in altered charge and
      hydropathicity properties of the presumed Ag binding site. In this way, we have
      been able to demonstrate that human T cell repertoire development in the absence
      of MHC class II expression results in a circulating CD4+CD8- T cell population
      bearing TCRs with altered CDR3 profiles. Such altered profiles are likely to be a
      direct reflection of the lack of MHC class II-mediated selection processes in
      these BLS patients.

PMID- 8558016
TI  - Target-induced inactivation and cell death by apoptosis in a subset of human NK
      cells.
AB  - Interaction of sensitive target cells with NK cells results in both positive and
      negative signaling. Positive signaling results in the induction of NK
      cytotoxicity and sensitization for IL-2-mediated proliferation and secretion of
      cytokines. Negative signaling prevents the NK cells from recycling for
      cytotoxicity. Functional inactivation is restricted to the NK-target conjugate
      subset sparing the nonconjugating free NK subset. The mechanism of target-induced
      inactivation of NK cells was examined in cell-sorted and purified conjugates. The
      conjugates were subdivided into two fractions; in one fraction the NK cells were
      dissociated from the target (NKDC), and in the other fraction the conjugates were
      not disturbed (NKC). After coculture overnight with IL-2, the cytotoxic function
      of NKC was not augmented although a subpopulation proliferated and secreted TNF
      alpha and IFN-gamma into the supernatant. In contrast, NKDC cytotoxic activity
      was enhanced by IL-2, but proliferated poorly and did not secrete TNF-alpha or
      IFN-gamma following IL-2 activation. The phenotype of the inactive NKC was found
      to be CD16dim/- CD692+ CD11b2+. Target-mediated inactivation correlated with
      target cell sensitivity to NK cytotoxicity. Furthermore, a significant fraction
      of NK cells in the NKC was programmed for cell death by apoptosis. Altogether,
      these results demonstrate that sensitive targets inactivate NK cells for
      cytotoxicity resulting in loss of NK cells. Furthermore, the results suggest that
      signaling for cytotoxic function by target cells is not linked to signaling for
      proliferation and secretion of cytokines by NK cells.

PMID- 8558017
TI  - Oral antigen inhibits priming of CD8+ CTL, CD4+ T cells, and antibody responses
      while activating CD8+ suppressor T cells.
AB  - We have been investigating the mechanisms by which exogenous protein Ags activate
      CD8+ T cells. Previously, we have shown that OVA primed CTL precursors in vivo if
      administered as an emulsion with an adjuvant such as CFA. Such CTLs inhibit
      development of Ab responses when adoptively transferred into syngeneic mice.
      Thus, CD8+ CTL are immunosuppressive. These studies were initiated to determine
      whether CD8+ suppressor T cells were cytolytic T cells. Oral administration of
      protein Ags is a well-established method for inducing tolerance in humoral and
      delayed hypersensitivity responses which is associated with development of CD8+
      suppressor T cells. OVA was chosen as a model Ag because it has been used
      extensively in oral tolerance studies, and target cells expressing the OVA gene
      are well characterized. Our data show that multiple, intragastric doses of native
      OVA inhibited priming of CD8+ CTL precursors and also inhibited CD4+ T cells and
      Ab responses. Oral OVA inhibited CTL priming in mice immunized with OVA-loaded
      EL4 cells, OVA-expressing transfectants, or OVA in CFA. The observed tolerance is
      specific to the orally administered Ag. Although oral OVA did not prime CTL
      precursors, it did activate spleen cells that transferred unresponsiveness to
      naive syngeneic mice. Suppression was mediated by CD4-CD8+ T cells. These CD8+
      suppressor T cells were phenotypically distinguished from CTL by reactivity with
      a mAb that recognizes activated suppressor T cells.

PMID- 8558018
TI  - An inducible lymphocyte nuclear Ca2+/Mg(2+)-dependent endonuclease associated
      with apoptosis.
AB  - Apoptotic cell death is typically accompanied by internucleosomal chromatin
      fragmentation. Although a number of candidate enzymes have been proposed, there
      is as yet no direct evidence for the involvement of any particular endonuclease
      in this process. Here we demonstrate the existence of an endonuclease(s) that is
      up-regulated during apoptotic T cell death. The endonuclease(s) is located in the
      nucleus, and its activity is increased up to eightfold by a variety of stimuli or
      conditions that induce apoptosis in T cell hybridomas and thymocytes. Treatments
      that prevent TCR-mediated apoptosis, such as cyclosporin A or concomitant
      administration of glucocorticoids, also prevent the induction of enzyme activity.
      The endonuclease activity is associated with three molecular forms, designated A,
      B, and C, with apparent M(r) of 49K, 47K, and 45K, respectively, and constitutes
      the major endonuclease activity in T hybridoma cells. From A exists in resting
      cells, and its activity is increased threefold after the induction of apoptosis.
      Forms B and C are absent in resting cells and are induced up to 20-fold after
      stimuli that lead to apoptosis. All three forms are Ca2+/Mg2+ dependent and are
      inhibited by Zn2+. This enzyme(s) introduces double strand breaks and single
      strand nicks into supercoiled plasmid DNA, demonstrating the mode of DNA
      fragmentation characteristic of products of apoptotic chromatin degradation. The
      enzyme(s) produces DNA fragments with 5'-P and 3'-OH terminals, also consistent
      with apoptotic chromatin degradation. Finally, enzyme solubilized from cells
      activated to die cleaves chromatin in nuclei isolated from unstimulated T
      hybridoma cells, yielding the classic DNA ladder. Because of its biologic
      properties, we named this enzyme(s) inducible lymphocyte Ca2+/Mg(2+)-dependent
      endonuclease, or ILCME. Because inducible lymphocyte Ca2+/Mg(2+)-dependent
      endonuclease possesses the key features predicted for an apoptosis-specific
      enzyme, it is a new candidate for an enzyme(s) that participates in DNA cleavage
      in apoptotic T cells.

PMID- 8558019
TI  - Chemokines regulate T cell adherence to recombinant adhesion molecules and
      extracellular matrix proteins.
AB  - Chemokines are a family of structurally related, low m.w. proteins that regulate
      leukocyte migration both in vitro and in vivo. By virtue of their target cell
      specificity, chemokines have the potential to selectively recruit leukocyte
      subpopulations into sites of inflammation during the genesis of an immune
      response. Chemokines have been shown to induce leukocyte adhesion to endothelium,
      to facilitate trans-endothelial passage, and to direct cell migration along a
      protein gradient (chemotaxis). The chemokines (macrophage inflammatory protein-1
      alpha, macrophage inflammatory protein-1 beta, RANTES, and IFN-inducible protein
      10) have recently been reported to be chemotactic for T cells. We have
      investigated the potential activity of these proteins in regulation of T cell
      adhesion. These chemokines induce T cell adhesion to purified, recombinant human
      adhesion molecules (rhICAM-1, rhVCAM-1) and to ECM proteins: fibronectin,
      collagen, and laminin. The chemokine-induced adhesion process occurs rapidly, is
      dose-dependent, and appears to be mediated via beta 1 and beta 2 integrins. The
      enhanced T cell adhesion is not associated with an increased surface expression
      of adhesion proteins, suggesting that chemokines stimulate the development of a
      high affinity state in the integrin molecules. Our findings provide in vitro
      evidence of a critical role for chemokines in T cell adhesion to endothelial
      adhesion molecules and ECM proteins, thereby promoting haptotactic migration of T
      cells to sites of inflammation in vivo.

PMID- 8558020
TI  - Requirement for phosphatidylinositol 3'-kinase to protect hemopoietic progenitors
      against apoptosis depends upon the extracellular survival factor.
AB  - Hemopoietic growth factors promote survival of progenitor cells by preventing
      their apoptotic death. Recently, phosphatidylinositol 3'-kinase (PI 3-kinase) has
      been shown to be integral in the pathway by which insulin and nerve growth factor
      prevent apoptosis. In this work, we show that IL-3-dependent FDCP-1/Mac-1 murine
      hemopoietic progenitors express receptors for another growth factor, insulin-like
      growth factor-I (IGF-I), and that both IL-3 and IGF-I stimulate PI 3-kinase
      activity. We then demonstrate that IGF-I shares with IL-3 the properties of
      significantly promoting proliferation and enhancing survival of myeloid
      progenitor cells at concentrations as low as 3 ng/ml. IL-3 and IGF-I efficiently
      promote cell survival in the presence of inhibitors of either RNA synthesis
      (actinomycin D) or mitosis (mitomycin C), suggesting that both ligands promote
      survival by a process that is largely independent of RNA synthesis. To determine
      whether PI 3-kinase mediates IL-3- and IGF-I-induced inhibition of apoptosis,
      FDCP-1/Mac-1 cells were incubated with the PI 3-kinase inhibitor, wortmannin.
      While wortmannin inhibited both basal and IGF-I- and IL-3-induced PI 3-kinase
      enzyme activity, it did not affect the ability of IL-3 to protect FDCP-1/Mac-1
      cells from apoptosis, even though it abrogated the IGF-I-induced inhibition of
      apoptosis. These data demonstrate that even though activation of PI 3-kinase is a
      pleiotropic feature of both IL-3 and IGF-I receptors in myeloid progenitors,
      prevention of apoptosis by IL-3 but not IGF-I is independent of PI 3-kinase.
      Survival of hemopoietic progenitors is therefore maintained by at least two
      different intracellular signaling pathways, one requiring PI 3-kinase and one
      that does not.

PMID- 8558021
TI  - Isolation and characterization of cell lines with genetically distinct mutations
      downstream of protein kinase C that result in defective activation-dependent
      regulation of T cell integrin function.
AB  - beta 1-integrins expressed on resting T cells support only minimal adhesion to
      integrin ligands. T cell activation through multiple stimuli, including phorbol
      ester treatment and Ab cross-linking of the CD3/TCR complex, results in a rapid
      and transient switch in integrin function from low to high avidity binding. The
      exact nature of the intracellular signals involved in this avidity switch remain
      poorly defined, but the ability of phorbol esters to induce such up-regulation
      implicates a role for protein kinase C (PKC). We have used a genetic approach to
      identify factors other than PKC that regulate activation-dependent beta 1
      integrin function on T cells. We isolated mutants of the Jurkat T cell line that
      express beta 1- and beta 2-integrins but do not exhibit increased integrin
      activity in response to PMA stimulation or CD3 cross-linking. PKC activity
      appears to be normal in the mutants. One mutation is associated with an altered
      form of the mitogen-activated protein kinase ERK1 and an inability to produce IL
      2. Another mutant with defective integrin function has IL-2 production intact.
      Complementation analysis verified that these two types of mutants are genetically
      distinct. Thus, two mutations downstream of PKC have been identified that alter
      the process of integrin regulation without affecting T cell viability or
      proliferative capacity. These mutants represent novel reagents for the
      identification of integrin regulatory factors and indicate possible sites of
      pharmacologic intervention that could prevent integrin-dependent migration and
      localization in the process of inflammation, while leaving other T cell functions
      intact.

PMID- 8558022
TI  - Long-term culture of triple-negative thymocytes.
AB  - The role of the thymic microenvironment in regulating events that occur
      subsequent to the acquisition of CD4, CD8, and the TCR, such as positive and
      negative selection, has been studied extensively. However, comparatively less is
      known about how thymic stromal cells regulate growth and differentiation within
      the CD4-CD8-TCR- triple negative (TN) cell compartment. Long-term culture systems
      have played a pivotal role in the understanding of microenvironmental regulation
      of myelopoiesis and B lymphopoiesis, but establishment of comparable cultures for
      T lineage cells has proved challenging. This report describes a culture system in
      which a thymic stromal cell line preferentially supports the long-term growth of
      TN thymocytes. In addition to demonstrating that TN cells have a considerable
      proliferative potential, the results provide insights into the effects of IL-7 on
      the growth and/or survival of TN cells and its role in regulating TCR gene
      rearrangements. The ability of the cultured TN cells to mature into CD4- and/or
      CD8-expressing thymocytes, some of which express TCR-alpha beta, suggests that
      the system will be valuable for the identification of microenvironmental stimuli
      that regulate the maturation of TN cells.

PMID- 8558023
TI  - Thymic stromal cells can support B cell differentiation from intrathymic
      precursors.
AB  - T lineage cells are the predominant intrathymic population, but low numbers of
      thymic B cells are also present in the thymus. Recent studies describing the
      contribution of thymic B cells to the shaping of the T cell repertoire have
      raised the question as to whether they are produced intrathymically and the
      potential role of the thymic stroma in this process. During the course of studies
      aimed at testing the B cell developmental potential of CD4-CD8-CD3/TCR- triple
      negative thymocytes present in a newly developed, stromal cell-dependent, long
      term culture system, the ability of selected thymic stromal cells to support
      distinct stages of B cell development was revealed. Some thymic stromal cell
      lines maintained cells with B cell developmental potential but could not support
      their differentiation, while other selected lines efficiently supported the
      development of surface IgM-expressing cells from triple-negative precursors.
      Thymic surface IgM+ B cells were generated most efficiently from thymocytes
      harvested from relatively young mice. Taken together, the results of this study
      demonstrate that the thymic microenvironment exhibits a functional heterogeneity
      in its ability to support different stages of B cell development.

PMID- 8558024
TI  - Medullary thymic epithelial cells induce tolerance to intracellular proteins.
AB  - The role of the medullary thymic epithelial cells in tolerance induction to MHC
      class I restricted self peptides has been analyzed by studying the beta
      galactosidase (beta-gal)-specific cytotoxic T cell response of a transgenic mouse
      expressing beta-gal in the thymus, skin, and central nervous system (Tg beta-gal
      mouse). Our results showed that: 1) beta-gal expression in the thymus was limited
      in a subpopulation of medullary epithelial cells, and bone marrow-derived thymic
      cells were beta-gal-1; 2) Tg beta-gal mice did not mount an anti-beta-gal CTL
      response even in the presence of exogenous IL-2, while Tg beta-gal-->B6 chimeras
      responded to beta-gal as strongly as NTg beta-gal mice; 3) Tg beta-gal mice did
      not generate CTL against the immunodominant Kb-restricted beta-gal 497-504
      peptide; 4) tolerance was due to the thymic epithelial cells that expressed beta
      gal because nude mice grafted with thymus from Tg beta-gal mice were also unable
      to respond to beta-gal; 5) the Tg beta-gal mouse-derived beta-gal+ medullary
      epithelial TEC.X10 line presented the Kb-restricted beta-gal 497-504 epitope. In
      conclusion, these results demonstrate that medullary thymic epithelial cells
      induce a complete tolerance towards class I-restricted self peptides presented on
      their own surface.

PMID- 8558025
TI  - Immune or normal gamma delta T cells that assist alpha beta T cells in
      elicitation of contact sensitivity preferentially use V gamma 5 and V delta 4
      variable region gene segments.
AB  - In the current study, we confirmed previous findings suggesting that gamma delta
      T cells were involved in the successful adoptive cell transfer of contact
      sensitivity (CS) by alpha beta CS-effector T cells. In this study, we used
      hamster anti-mouse gamma delta-TCR mAb treatment of CS-effector T cells, followed
      by enrichment and removal of the gamma delta T cells with goat anti-hamster Ig
      linked magnetic beads, or by addition of hemolytic rabbit C. This removal of
      gamma delta T cells abrogated adoptive cell transfers of CS, despite the presence
      of alpha beta T cells that are known to mediate CS. FACS analysis documented
      enrichment of gamma delta T cells rising from 1 to 2% of the starting cells, to
      60 to 95% of the magnetic bead adherent cells. Adoptive cell transfer of CS was
      reconstituted by adding back to the alpha beta cells, highly enriched gamma delta
      cells attached to anti-gamma delta-TCR magnetic beads. Not only were gamma delta
      enriched T cells from sensitized mice able to assist immune CS-effector alpha
      beta T cells, but gamma delta T cells from normal nonimmune mice also had CS
      assisting activity, and furthermore, neither were MHC-restricted in this
      function. Thus, CS-assisting gamma delta T cells were present endogenously in
      normal mice without prior immunization, and acted without Ag specificity and
      without MHC restriction, to assist CS-effector alpha beta T cells. Similar
      studies, with hamster mAbs specific for V gamma and V delta portions of gamma
      delta-TCR, demonstrated that the gamma delta T cells that assisted the CS
      effector alpha beta T cells preferentially expressed V gamma 5 and V delta 4 in
      their TCR. PCR analysis on extracted mRNA showed that V gamma 5 and V delta 4
      gene segments indeed were rearranged and expressed in the sensitized and normal
      lymph nodes; and one-and two-color FACS analysis of magnetic bead-fractionated
      cells suggested that V gamma 5 and V delta 4 were expressed on the same T cells.
      In summary, these results demonstrated that V gamma 5+, V delta 4+, gamma delta T
      cells were needed to assist alpha beta effector T cells in the adoptive cell
      transfer of CS.

PMID- 8558026
TI  - Thymus-leukemia antigen interacts with T cells and self-peptides.
AB  - The functional role of the class Ib thymus-leukemia (TL) Ag expressed within the
      thymic cortex and intestinal mucosa of the mouse remains unknown. In an approach
      to elucidate the potential functionality of TL, we developed transgenic mice that
      ectopically express the H-2T18d gene product on essentially all nucleated cells
      through the control of a heterologous H-2Kb gene promoter. Transgenic mice
      demonstrated an increase in the number of CD4+ lymphocytes within the thymus and
      lymph nodes; these cells displayed an altered T cell receptor repertoire possibly
      suggesting a role for the ectopically expressed TL protein. The TL protein
      additionally displayed the characteristics of a bona fide transplantation Ag,
      because skin grafts from transgenic animals onto MHC- and minor
      histocompatibility Ag-matched nontransgenic recipient mice resulted in a rapid
      and vigorous immunologic rejection of the allograft. In MLR studies, transgenic
      stimulator cells induced the proliferation of responders to a level intermediate
      between genetically identical and H-2-disparate responder-stimulator
      combinations. The TL protein was also capable of stimulating cytotoxic T
      lymphocytes, thereby resulting in specific lysis of TL+ target cells. Further
      data demonstrated that the TL protein assembles with peptides that are modified
      at the amino terminus, and that TL retains these molecules at the cell surface.
      Together, these data suggest that H-2T18d is capable of interacting with T cells
      via a bound peptide. These data further support the possibility that TL may
      subserve a specialized function within the immunologic system.

PMID- 8558027
TI  - The role of BALB/c donor CD8+ lymphocytes in graft-versus-host disease in (BALB/c
      x A/J)F1 (CAF1) mice.
AB  - To investigate the role of donor T lymphocyte subsets in the development of
      chronic graft-vs-host disease (GVHD) induced in (BALB/c x A/J)F1 (CAF1) mice by
      injecting BALB/c lymphoid cells, we analyzed the effect that CD8+ cell removal
      from donor inoculum has on the manifestation of the disease. Compared with age-
      and sex-matched CAF1 mice injected with whole lymphocyte inoculum, CAF1 mice
      injected with CD8(+)-depleted inoculum exhibited: 1) a higher incidence and
      exacerbation of nephritis by immunocomplexes; 2) higher (five- to sevenfold)
      spontaneous IL-4 production; 3) higher frequency titer and precocity of anti
      dsDNA, anti-histone, and IgM and IgG rheumatoid factors; 4) a dramatic change in
      the frequency and titer of anti-U1 small nuclear ribonucleoprotein Abs; and 5) a
      markedly decreased engraftment (10- to 15-fold) on BALB/c donor lymphocytes. In
      contrast, rheumatoid arthritis-like disease, a later clinical manifestation of
      the GVHD in CAF1 + BALB/c model, is not present in the CD8(+)-depleted model
      (CAF1 + CD8-BALB/c). Considered together, these data suggest that CD8+ donor T
      lymphocytes play an important role in the degree of chimerism, modulation of the
      response to autoantigens, and clinical aspects developed in the GVHD model
      presented here.

PMID- 8558028
TI  - [Simplified vesico-urethral anastomosis after radical retropubic prostatectomy
      for cancer. A preliminary comparative study].
AB  - The authors have done a prospective non randomized study to compare two methods
      of radical retropubic prostatectomy, without bladder neck preservation (Group 1 =
      30 patients) or with bladder neck preservation (Group 2 = 15 patients).
      Anastomosis was simplified for the 15 patients with bladder neck preservation
      according to the Vest suture procedure. A comparative urodynamical study was
      performed with each group. Selection for one or the other technique was made by
      the personal choice or every surgeon. Results were similar for pre operative
      clinical staging, Gleason score with both groups. There was no significant
      difference in survival, progression of the disease and three month PSA level as
      those of the last follow-up visit (18-96 months). There was no difference between
      the 2 groups regarding operative time, blood loss, urethral catheterization time,
      drainage output and mean hospitalisation time. The only significant difference
      was the number of post operative transfused blood units in the Vest suture group
      (p < 0.001). There were no positive margin on the preserved bladder neck in group
      2, even if there was finally an understaging or another apical positive margins.
      Complications were not significantly different in the two groups with 10 bladder
      neck strictures in the group 1 (33%) and only 2 in the group 2 (14.2%) (NS).
      Complete continence rate was 73.3% and 64.2% respectively (NS). Bladder neck
      incision was never followed by incontinence. On urodynamical study, 9 cases in
      each group were compared and both were similar but there was a tendency to a
      higher urethral pressure in group 2. Comments pointed out that bladder neck
      preservation and simplified Vest traction suture did not give more post operative
      nor carcinological complications than classical technique with direct separate
      stitches sutures. Disease progression, continence and bladder neck stricture
      rates were compared to literature. The urodynamical results were the same as
      those observed by others studies.

PMID- 8558029
TI  - [Resistance to chemotherapy in cancers of the kidney and therapeutic
      perspectives].
AB  - Usual treatments combining surgery, radiation therapy, chemotherapy and
      hormonotherapy are poorly effective. The immunotherapy gave and objective
      response rate of 25% but is associated with many side effects. Multidrug
      resistance (MDR) can be explained, in part, by an mdr1 gene overexpression in
      renal carcinoma. The MDR is related to expression of a 170 Kda membrane
      glycoprotein, the so-called P glycoprotein (Pgp). This protein is able to extrude
      from cytoplasm drugs with various structures and mechanisms. Reversal compounds
      capable of inhibiting Pgp, given with antineoplastic drugs, could be able to
      increase their intracellular concentrations. Nevertheless, renal cell carcinomas
      are characterized by their multifactorial resistance and a better knowledge in
      this field will allow to design new circumvention resistance to chemotherapy.

PMID- 8558031
TI  - [Posterior urethral valves in children. Apropos of 22 cases].
AB  - We reviewed 22 cases of posterior urethral valves over a five year period
      (January 1986 to December 1990). We looked at initial management before referral
      to the urologist, treatment and those factors that influence the outcome. We
      found that nosocomial infection from catheters was the major source of morbidity
      and mortality. Other determinants of outcome included postobstructive diuresis
      and the presence of refluxing or obstructing megaureters. The age of the patients
      was not as important as the degree of obstruction in this group of patients. We
      recommend percutaneous cystostomy as initial management for these patients as
      opposed to urethral catheterisation. This should be followed by antegrade or
      retrograde valve ablation one week later depending on the size of urethra.

PMID- 8558030
TI  - [New technique of hypothermic renal protection in surgery for tumor of the
      solitary kidney].
AB  - Ex-situ protection of donor organs for transplantation with initial cold
      perfusion is routinely used. The superiority of the Histidin-Tryptophyn
      Ketoglutarate solution (HTK) has been demonstrated in animal models and clinical
      use. On the other hand, nephron sparing surgery for surgical or functional
      solitary kidneys has been proved effective for many years. Due to widely used
      ultrasound and computerized tomography, the incidence of small renal tumors has
      increased. Therefore, new concepts in conservative renal surgery are gaining more
      popularity. In this study we report about 11 patients with renal masses in a
      functional solitary kidney. For the first time, all enucleations were performed
      with continuous in-situ perfusion with HTK-solution. Despite extensive tumors
      with central extension, complete in-situ tumor resection and kidney
      reconstruction were possible. There were no intraoperative complications.
      Postoperatively, one kidney was lost secondary to renal artery embolism. Urine
      production started within one hour postoperatively in all cases. No further
      patient needs haemodialysis. Postoperatively, renal function was largely
      unchanged except for a transient minor elevation of the serum creatinine. There
      were no changes of serum creatinine. There were no changes of serum electrolytes
      and no cardiac failures under HTK. The indication, the surgical procedures and
      the first clinical results of continuous in-situ perfusion with HTK-solution for
      conservative renal surgery are presented.

PMID- 8558032
TI  - [Urinary calculi, consisting of dehydrated calcium phosphate. Clinical,
      biological, radiologic aspects, clinical course and management].
AB  - Seventeen cases of urinary calculi analyzed by infrared spectrophotometry were
      found to be composed entirely or nearly entirely of bihydrated calcium
      hydrophosphate. The observations are summarized here. This type of stone occurs
      with a frequency of about 1% (0.85% in our experience) of all urinary calculi,
      predominantly in men (14 of our 17 cases). Diagnosis is based on the physical and
      chemical analysis of the stone and on infrared spectrophotometry. Most of these
      stones are pure or nearly pure compounds. The macroscopic aspect of the stones or
      fragments of stones can guide diagnosis. These stones are cream coloured stones
      with a smooth regular outer surface. Broken fragments show the same cream colour,
      sometimes with strips radiating from the centre of the fracture surface.
      Radiologically, these stones are homogeneously radio-opaque, often oval-shaped
      with a regular outline. Blood tests can demonstrate suspected or proven
      hyperparathyroidism (4 out of 10 cases in our 17 observations) with
      hypercalcemia, hypophosphatemia and hypercalciuria. Complementary examinations
      may be needed to search for a parathyroid adenoma. With or without
      hyperparathyroidism, 24-h urinalysis usually shows hypercalciuria up to ro over
      500 to 600 mg/24 h. Crystallization usually occurs in the upper urinary tract, in
      the bladder or in indwelling catheters. These stones are extremely hard and are
      difficult to break in vitro. To be successful, lithotripsy requires prolonged
      treatment: up to 3000 to 6000 shockwaves at 22-23 kv with the Dornier apparatus.
      Despite the notion of hypercalciuria, the pathogenesis of bihydrated calcium
      hydrophosphate calculi remains to be elucidated.

PMID- 8558033
TI  - [Stereology of the human epididymis in different groups of age: fetus, children,
      adolescents and elderly].
AB  - The importance of abnormalities of function and epididymis structure in the
      etiology of male infertility is still not well understood. We studied 52
      individuals distributed in five age groups: fetuses, children, adolescents,
      adults and the elderly. The region of the body of epididymis was obtained by
      autopsy and immediately fixed by immersion in a solution of 10% buffered
      formaldehyde, embedded in paraffin and histologically prepared. The samples were
      observed under an optic microscope. Test-points were counted in 12 random
      microscopic fields with the M42 test-system. The following stereological
      parameters were determined: ductal area, volumetric densities (Vv) of the duct,
      smooth muscle, connective tissue, epithelial duct and blood vessels. The main
      results distinguished by those whose averages were statistically significant (p <
      0.05), showed that the ductal area is 9.7 times greater in the
      adolescent/adult/elderly group than the children's group. The Vv of the lumen of
      the epididymis duct occupies 11.7% of the epididymis body in the fetal period,
      5.3% in the child and in individuals after puberty this figures reaches more than
      15%. The Vv of smooth muscle occupies 28.3% of the body of the epididymis in the
      fetus and 35.9% in children, but after puberty this figures stays around 22%. The
      Vv of the connective tissue occupies 26% in prenatal life, 37% in children, and
      after puberty these figures range from 21 to 27.5%. Comparing the results of the
      adult group with that of the elderly group there is an increase in the volumetric
      density of the connective tissue by 18.1%. In conclusion, the epididymal duct
      area and the Vv of the ductal lumen, smooth muscle and connective tissue were
      significant comparing the different groups. However, the quantitative relative
      differences of the duct's epithelium and the blood vessels were not significant
      comparing these groups. The study of quantitative aspects of the normal human
      epididymis can increase our knowledge about male fertility.

PMID- 8558034
TI  - [Uretero-vesival rupture with vaginal fistula following pelvic fracture. Value of
      early diagnosis and emergency surgery].
AB  - Traumatic fracture of the pelvis led to the rare combination of urethra and
      bladder rupture and fistulization into the vagina. This unusual lesion can go
      undiagnosed initially and must be properly identified during the emergency
      gynaecology and urology examination. Tissue damage involved nearly the entire
      length of the urethra including both the smooth and striated sphincters.
      Reconstructive surgery produced good anatomic and functional results.

PMID- 8558035
TI  - [Tumor of the spermatic cord and the gonadal stroma of the testis. Apropos of a
      case in a 19-year old man].
AB  - A Sertoli cell mesenchymal tumour was observed in a 19-year-old male. The
      prognosis of this rare tumour is good.

PMID- 8558036
TI  - [Role of ultrasound lithotripsy in the treatment of lithiasis of the lower
      urinary tract. Apropos of 38 cases].
AB  - Between February 1989 and February 1994, 38 patients with lower urinary tract
      lithiasis were treated by ultrasonic lithotripsy. Mean size of the stone was 23 x
      19 mm, extreme being 5 mm-50 mm (over 20 mm in 27 patients). Transurethral
      lithotripsy has been performed in 36 patients, and percutaneous cystolithotripsy
      in 2 patients. Some desintegration was complete in 37 cases, and the only failure
      was a case in which the stone was too hard. Morbidity was zero. Ultrasonic
      lithotripsy for urethral and bladder stones appears to be a safe, effective and
      simple method of treatment.

PMID- 8558037
TI  - [Urinary excretion of leucine aminopeptidase after extracorporeal shock wave
      lithotripsy].
AB  - Extracorporeal shock-wave lithotripsy (ESWL) is the treatment of choice in the
      majority of urinary calculi. In experimental and clinical research it has been
      shown that the method has short-term deleterious effects on renal function.
      Several factors, such as urinary tract infection (UTI), the site of the stone,
      pre-existing renal abnormalities, the number and intensity of the shock waves may
      influence the extent of the damage. The aim of this study was to measure the
      excretion of the renal microsomal enzyme, leucinaminopeptidase (MLAP) as
      expression of renal damage following ESWL. Our study shows that there was a
      significant elevation in urinary excretion of MLAP immediately after ESWL,
      especially in patients with UTI. These results indicate that UTI may be one of
      the risk factors for aggravation of renal damage after ESWL. However, these
      changes are transient and expressed less than in patients with light renal trauma
      arising because of other external influence.

PMID- 8558038
TI  - [Limitations of ultrasonography in the detection of small cancers of the left
      kidney].
AB  - Renal ultrasound seems to be more difficult on the left than on the right side.
      In a retrospective analysis of 343 patients in whom a radical nephrectomy for
      renal tumor diagnosed by abdominal ultrasonography had been carried out, we
      analyzed the characteristics of these tumors. TNM classification was used. Right
      kidney tumors (n = 170) were smaller than the left ones (n = 172), 58 +/- 31.7 mm
      and 66.8 +/- 31.5 mm respectively, the difference being statistically significant
      (p = 0.01). Right kidney tumors of a less advanced stage (p < 0.05). Asymptomatic
      renal tumors were found more frequently on the right side (58.7%) than on the
      left (41.3%) (p = 0.03) and were smaller on the right (44 mm +/- 19.6 vs 54.5 mm
      +/- 27.2) (p = 0.04). In conclusion, Ultrasound exploration of the left kidney
      seems to be more difficult, mostly because the exploration of the right kidney is
      facilitated by the acoustic window of the liver.

PMID- 8558039
TI  - [Cancer of the testis in cryptorchidism. Apropos of 5 cases].
AB  - Five cases of cancer of the testicle in patients with cryptorchidism are
      presented. In one case the tumour occurred 16 years after cure for cryptorchidism
      at 15 years of age. In the other cases, the tumour developed on a testicle in an
      inguinal or intra-abdominal position. In two cases, it was impossible to remove
      the tumour which had developed on an intra-abdominal position. These patients
      died. These cases emphasize the importance of surgical cure in all cases of
      cryptorchidism, preferable before the age of 2 years, in order to improve
      functional prognosis and reduce the risk of cancerization. The gravity of cancer
      of the testicle in cases of cryptorchidism is often discovered too late.

PMID- 8558040
TI  - [A new trocar for suprapubic urinary drainage].
AB  - Most of the trocars provided with systems for suprapublic puncture are not
      entirely acceptable due to inadequate technical development. Since suprapublic
      trocars are particularly useful in clinical practice, we developed a new type of
      trocar with several improvements. The tip of the new trocar has three functional
      parts. The first third is a hard very sharp lancet which perforates the tissue
      layers like a scalpel. The second third of the tip is more flexible and cuts a
      half-circle. The last third has a smooth edge which separates and dilates the
      borders of the opening. This eliminates the punch effect and ensures a constant
      contact between the body of the trocar and the catheter placed within its central
      groove. The trocar has a continuous curve between its dilating part and the body
      for smooth insertion. Entry is controlled with a handle, thus avoiding accidental
      lesions. Since the tissues are elastic, the wound closes spontaneously when the
      trocar is removed. The advantages of the new puncture system have been confirmed
      with clinical data.

PMID- 8558041
TI  - [Urogenital tuberculosis. Diagnostic aspects].
AB  - Urogenital tuberculosis still represents a major urologic problem in the northern
      part of Africa, and it is a serious disease because its diagnosis is usually
      late. Furthermore, the affection is frequently bilateral, which may cause the
      renal failure. 86 cases of urogenital tuberculosis have been reviewed. Our
      patients were young adults (average age: 34 year old). Cystitis is the most
      frequent sign (74%), hematuria, lumbar pain, genital signs and nephrologic signs
      are not rare. Urine was negative in 46 patients, and amicrobial leucocyturia was
      present in 24 cases. Diagnosis relies on a range of signs, especially intravenous
      pyelography that has an important place. Endoscopic biopsy did confirm the
      diagnosis of tuberculosis in 12 patients. Generally, definitive diagnosis was
      based on the histologic study of the operative specimen.

PMID- 8558042
TI  - [Urothelial tumor of the bladder in children].
AB  - A papilloma of the bladder was discovered in 10-year-old child who presented with
      haematuria. The review of the literature from 1955 produced 131 similar cases.
      The particular situation of this usually adult tumour in paediatric patients was
      emphasized by this case and those reported in the literature: good prognosis,
      rare invasion, lower rate of recurrence than in the adult and habitual
      effectiveness of endoscopic resection.

PMID- 8558043
TI  - [Ureterovaginal fistulas: treatment with preservation of the distal ureteral
      segment. Apropos of 3 cases].
AB  - The authors report on the treatment of 3 ureterovaginal fistulas using a method
      preserving the segment of ureter below the fistula. In one case, the fistula was
      successfully managed by ureteroscopic placement of ureteral stent. Two other
      cases were managed with ipsilateral ureteroureterostomy, where the segment of
      ureter below the fistula was identified using ureteroscopic perforation of this
      segment.

PMID- 8558044
TI  - [Bilateral fracture of the corpus cavernosum with complete rupture of the
      urethra].
AB  - About a case of complete rupture of the urethra associated to bilateral fracture
      of the corpus cavernosa following manipulation of the penis in erection, we
      stress the interest of an early surgical treatment, which permits a precise
      lesional diagnosis and an immediate reparation of the lesions. It is even the
      best warrant of a correct functional recovery.

PMID- 8558045
TI  - [Adrenal myelolipoma. Apropos of 3 cases].
AB  - The authors report 3 cases of adrenal myelolipoma arising in 3 women who were
      respectively 36, 47 and 48 year old. The diagnosis was made on the surgical
      specimen in 3 cases, and the clinical symptomatology was dominated pain seen in
      all 3 cases. 2 patients have presented hypertensive access. After surgery, the
      evolution was favourable in all 3 cases.

PMID- 8558046
TI  - Medical licensure for osteopathic physicians in Louisiana: why the State Board of
      Medical Examiners should accept the NBOME.
AB  - The Louisiana State Board of Medical Examiners does not recognize the examination
      offered by the National Board of Osteopathic Medical Examiners as a valid pathway
      to licensure, either directly or by endorsement. The State Board recognizes the
      United States Medical Licensing Examination (USMLE) as the appropriate
      examination for direct licensure. For licensure by endorsement, the State Board
      will license physicians who have passed any of the allopathic national licensing
      examinations. Osteopathic physicians do not take the USMLE or other allopathic
      licensing examinations because they test students on allopathic medical education
      and do not measure osteopathic medical training. Instead, osteopathic medical
      students take the examination offered by the National Board of Osteopathic
      Medical Examiners. The National Board of Osteopathic Medical Examiners' test is
      accepted by every other state and is an appropriate measure of the abilities of
      osteopathic physicians.

PMID- 8558047
TI  - ECG of the month. Deadly exposure? Ventricular tachycardia.

PMID- 8558048
TI  - October 1845 and 1895.

PMID- 8558049
TI  - Passive smoking.
AB  - One in three adults in the United States smokes. Smokers inhale one quarter of
      the smoke from cigarettes. But 75% of cigarette smoke is released into the
      environment. Nonsmokers are exposed to this environmental tobacco smoke and are
      at risk for disease. A growing body of literature supports the association of
      passive, involuntary, or secondhand smoking with human pathology. This discussion
      examines the makeup of environmental tobacco smoke and its role in causing human
      disease with a review of the literature relating environmental tobacco smoke to
      head and neck pathology.

PMID- 8558050
TI  - Progress against cancer...?!
AB  - Data from the population based cancer registry in Alberta, Canada as well as from
      the National Canadian Cancer registry were used to evaluate the outcome of
      oncologic treatment over the past 25 years. Age standardized incidence rates for
      all cancers combined, and for most individual cancer sites separately, show a
      continuous increase over time. Overall, the mortality rates have been increasing
      as well. Age specific trends in incidence and mortality show that, despite an
      increase in incidence rate, only in childhood cancers does a decrease in
      mortality exist. However, in patients aged 50 years or more at the time of the
      cancer diagnosis an increase in mortality was noted which actually exceeded the
      increase in incidence. Site specific analysis showed a decreasing trend in
      mortality for Hodgkin's disease, testicular cancer, stomach cancer, and melanoma
      (in females). A disturbingly increasing trend, specifically in women, existed for
      lung cancer mortality. It is projected that in women in Alberta mortality from
      lung cancer will surpass breast cancer mortality to become the number one cancer
      killer in women within the next few years. The overall 1-year, 2-year, and 5-year
      relative survival for all cancers combined remained constant over the 25-year
      period covered in this study. In conclusion, when analyzing the three indicators
      (incidence, mortality, and survival rates) of success in the fight against cancer
      no objective signs of progress could be found. Exceptions are the childhood
      cancers and relatively infrequent tumors such as Hodgkin's disease and testicular
      cancer. A plea is made for a shift in funding towards an increased emphasis on
      applied prevention programs and research.

PMID- 8558051
TI  - Ultrasonography in children of cystic abdominal masses not related to the
      genitourinary system.
AB  - A variety of cystic abdominal masses not related to the genitourinary tract may
      be encountered in the pediatric population. Ultrasound is the most informative
      imaging modality in the workup of these masses which include lymphangiomas,
      duplication cysts, enteric cysts, mesothelial cysts, pseudocysts, choledochal
      cysts, and gastrointestinal teratomas. The clinical and sonographic
      characteristics of these lesions are presented.

PMID- 8558053
TI  - Inaugural address.

PMID- 8558052
TI  - Louisiana neurosurgeons and the organ procurement shortage: a comparative
      analysis of perceptions, attitudes, and ethical values.
AB  - The supply of transplantable organs continues to fall behind demand. Knowledge of
      the perceptions, attitudes, and ethical values held by health care workers
      involved in the process is critical. This is particularly true of neurosurgeons
      because of their pivotal role in the procurement process. Survey data are used to
      compare neurosurgeons (n = 59) with emergency physicians (n = 125), critical care
      nurses (n = 267), and other physicians (n = 445). Analysis revealed that
      attitudes among those health care workers regularly involved with organ
      procurement and transplantation--neurosurgeons, emergency physicians and critical
      care nurses--tend to be similar. While there is general satisfaction and
      confidence in Louisiana's organ procurement and transplantation system, there are
      concerns. Perceived problems cited were: lack of support by the medical and lay
      community, high costs, potential profiteering, and conflict of interest. Other
      contentious issues include: organ request strategies, incentives for organ
      donations, racial bias, and presumed consent legislation. Debate and professional
      education in these areas are indicated.

PMID- 8558054
TI  - Intrafamilial spread of Epstein-Barr virus.
AB  - Epstein-Barr (EBV) virus is a common contagious illness encountered during
      childhood. It is spread through oral secretions, however it has a low rate of
      transmission within a family. This article reports EBV illness among three
      children in the same family.

PMID- 8558055
TI  - Carotid artery occlusion after dog bite.
AB  - The etiology of most penetrating neck injuries is caused by missiles or
      stabbings. Irrespective of the cause of injury, management strategies require
      that life-threatening injuries to underlying deep neck structures such as
      esophagus, trachea, or carotid artery be promptly identified. A case is reported
      in which occlusion of the common carotid artery resulted from a dog bite to the
      neck. The patient presented to the emergency department with four neck
      lacerations but lacked focal neurologic symptoms suggestive of such an underlying
      deep neck injury. The carotid injury was identified by preoperative angiography
      and was repaired with a reversed saphenous vein interposition graft. The patient
      had full recovery without neurologic sequela. While injuries to deep neck
      structures as a result of animal bites are rare, these patients should be
      evaluated according to accepted protocols to exclude or identify such life
      threatening injuries.

PMID- 8558056
TI  - Smokeless tobacco use among adults in Kentucky: 1994.
AB  - We assessed the 1994 prevalence of smokeless tobacco use among Kentucky adults >
      or = 18 years of age. 649 adults, contacted through a statewide random digit
      dialing procedure, completed an 18-minute telephone survey which included
      questions on current and former use of chewing tobacco and snuff. Overall, 4.5%
      of the sample (95% confidence interval [CI] = 2.95%-6.15%) claimed to currently
      use smokeless tobacco. Among males, 9.9% (95% CI = 6.1%-13.3%) claimed to
      currently use smokeless tobacco. Use of chewing tobacco exceeded snuff use by 2
      to 1. No women were current users of either chewing tobacco or snuff. A typical
      current user was male, was over 45 years of age, did not graduate from high
      school, and lived in a rural or Appalachian county of Kentucky. Former users
      comprised 17.3% of the sample; all but one of these were male. By the year 2000,
      the overall prevalence of smokeless tobacco must be reduced by half if Kentucky
      is to meet its public health objective that no more than 2% of Kentuckians use
      smokeless tobacco.

PMID- 8558057
TI  - Role of eosinophil-chemotactic C-C chemokines in cutaneous inflammation.
AB  - In the dermal sites of atopic skin, eosinophil (Eo) granule protein or more
      rarely intact Eos represent a characteristic histological feature. We addressed
      the question of whether lesional scales of patients with various eosinophilic
      skin disorders contain Eo attractant and tried to characterize it biochemically.
      In scales of a patient with drug reaction, heparin-binding Eo attractants could
      be identified. High-performance liquid chromatographic analyses together with
      specific ELISA and Western blot analyses revealed identity with RANTES. No other
      heparin-binding Eo chemotaxin could be identified. HPLC analysis of pooled
      lesional scale extracts of patients with atopic dermatitis showed fractions
      containing only weak heparin-binding Eo-chemotactic activity, which, however,
      showed RANTES immunoreactivity. In experiments to elucidate the putative cellular
      origin of Eo-attracting chemokines in human skin we investigated supernatants of
      atopic skin we investigated supernatants of atopic skin-derived T lymphocytes as
      well as supernatants of stimulated dermal fibroblasts for Eo-chemotactic factors.
      Unexpectedly, we did not find any heparin-bound Eo attractants in supernatants of
      stimulated cultured atopic skin-derived T lymphocyte clones, whereas fibroblasts
      produced RANTES as well as granulocyte-macrophage colony-stimulating factor.
      Therefore, fibroblasts are likely source of eosinophil attractant cells, which
      could contribute to the Eo infiltrate. Selectivity of the infiltrate might come
      from selective induction of RANTES and/or induction of other as yet unidentified
      Eo-specific chemokines.

PMID- 8558058
TI  - The vesiculo-vacuolar organelle (VVO): a distinct endothelial cell structure that
      provides a transcellular pathway for macromolecular extravasation.
AB  - The vesiculo-vacuolar organelle (VVO) is a recently described organelle found in
      the cytoplasm of endothelial cells that line tumor microvessels and normal
      venules. VVOs are grape-like clusters of interconnecting uncoated vesicles and
      vacuoles, bounded by trilaminar unit membranes, that span the entire thickness of
      vascular endothelium, thereby providing a potential trans-endothelial connection
      between the vascular lumen and the extravascular space. Macromolecular tracers
      preferentially cross hyperpermeable tumor microvessels through VVOs. The present
      investigation was undertaken to elucidate further the ultrastructure and function
      of VVOs in a murine ovarian carcinoma (MOT) and in normal venules. Morphometry
      revealed that VVOs were enormous cytoplasmic structures (median area, 0.12-0.14
      microns2 in single electron micrographs). Moreover, the individual vesicles and
      vacuoles that comprised VVOs were on average substantially larger than capillary
      caveolae and followed a non-normal distribution that was skewed to the right.
      Specimen tilting provided conclusive evidence that individual VVO vesicles and
      vacuoles communicated with each other and with the endothelial cells' plasma
      membranes by stomata, some of which were closed by diaphragms composed of a
      single membrane. Studies with two tracers, ferritin (FE, diameter approximately
      11 nm) and horseradish peroxidase (HRP, diameter approximately 5 nm), revealed
      that passage of macromolecules through VVOs was regulated at the level of
      stomatal diaphragms, thereby demonstrating a mechanism for controlling the
      passage of macromolecules across endothelial cells. Thus, compared with tumor
      microvessels, little circulating FE and HRP entered the VVOs of normal venular
      endothelium because stomata joining vesicles and vacuoles to each other and to
      the lumen and ablumen were closed. VVOs and their component vesicles/vacuoles
      were readily distinguished from endosomal organelles such as coated vesicles and
      multivesicular bodies, which also accumulated FE and HRP. Our findings indicate
      that VVOs provide a major pathway for the extravasation of circulating
      macromolecules across endothelia taller than capillary endothelium and suggest
      that upregulated VVO function accounts for the well-known hyperpermeability of
      tumor blood vessels.

PMID- 8558059
TI  - A synthetic peptide containing a predominant protein kinase C site within p47phox
      inhibits the NADPH oxidase in intact neutrophils.
AB  - In vivo loading of a synthetic peptide (peptide 4) corresponding to residues 314
      331 (RSRKRLSQDAYRRNSVRF) consistently diminished the oxidative burst in response
      to either phorbol 12-myristate 13-acetate (PMA) or formylmethionyl-leucyl
      phenylalanine and cytochalasin B (fMLP/CB) compared to other synthetic peptides
      derived from the p47phox sequence. The effects of peptide 4 were concentration
      dependent with respect to both PMA and fMLP/CB. In contrast, peptide 4 enhanced
      the oxidative burst in response to fMLP alone. Peptide 4 inhibited the PMA and
      fMLP-mediated phosphorylation of endogenous neutrophil cytosolic proteins
      including p47phox. The PMA-induced translocation of p47phox to the plasma
      membrane was diminished in neutrophils loaded with peptide 4. These data
      represent the first report of a synthetic peptide derived from p47phox that
      inhibits the NADPH oxidase in intact neutrophils and inhibits the protein kinase
      C-mediated phosphorylation of endogenous p47phox.

PMID- 8558060
TI  - Autocrine regulation of collagenase gene expression by TNF-alpha in U937 cells.
AB  - Tumor necrosis factor alpha (TNF-alpha) has been shown to induce the production
      of interstitial collagenase by fibroblasts and chondrocytes. We investigated the
      role of TNF-alpha in collagenase gene expression by U937 monocyte/macrophage
      cells. Transcription of the TNF-alpha gene was observed after 0.5 h of phorbol
      myristate acetate (PMA) stimulation. Collagenase mRNA expression was not observed
      until 5-7 h of activation with PMA. TNF-alpha was detected in the culture
      supernatants 2-3 h before transcription of the collagenase gene. Neutralization
      of TNF-alpha protein with anti-TNF-alpha antibodies significantly reduced
      collagenase mRNA expression. Protein kinase C (PKC) and protein tyrosine kinase
      (PTK) inhibition essentially abolished both PMA-induced TNF-alpha protein
      secretion and collagenase mRNA expression. Collagenase gene expression induced by
      exogenous TNF-alpha in U937 cells stimulated with a suboptimal concentration of
      PMA was suppressed by PTK, but not PKC, inhibition. The pyrrolidine derivative of
      dithiocarbamate, a potent inhibitor of nuclear factor-kappa B (NF-kappa B)
      activation, resulted in a marked reduction in collagenase gene transcription,
      however, no reduction of TNF-alpha secretion was noted. Anti-TNF-alpha antibodies
      inhibited PMA-induced NF-kappa B activation. These observations demonstrate an
      important role for TNF-alpha in the autocrine regulation of collagenase gene
      expression by U937 cells. Additionally, TNF-alpha-induced PTK and NF-kappa B
      activation were important in collagenase gene expression in this cell line.

PMID- 8558061
TI  - Activation and regulation of chemokines in allergic airway inflammation.
AB  - Allergic airway inflammation is characterized by peribronchial eosinophil
      accumulation with the submucosa surrounding the airway. The initial induction of
      immunoglobulin E (IgE)-mediated mast cell degranulation, up-regulation of
      adhesion molecules, and the production of inflammatory and chemotactic cytokines,
      leading to the infiltration of specific leukocyte subsets, is orchestrated in a
      sequential manner. The activation and degranulation of local mast cell
      populations is an immediate airway response mediated both by antigen-specific,
      surface bound IgE and by cytokine-induced activational pathways. Subsequently the
      infiltration and activation of effector leukocytes (neutrophils and eosinophils)
      mediated by the persistent activation of allergen-specific T cells leads to
      pathological manifestations within the lung and airway. The development of
      appropriate animal models to dissect the critical mechanisms involved in antigen
      induced airway pathology is crucial for the development of efficacious therapies.
      We have utilized a model of allergic airway inflammation induced by intratracheal
      challenge with parasite (Schistosoma mansoni) egg antigen in presensitized mice.
      This model has proven useful in the assessment of eosinophil recruitment and has
      identified key cytokines involved in leukocyte elicitation. These cytokines
      include interleukin-4 and elicitation. These cytokines include interleukin-4 and
      tumor necrosis factor, which appear to act as early response mediators, as well
      as C-C chemokines, macrophage inflammatory protein-1a, and RANTES, which act
      directly on eosinophil recruitment. In addition, we have found that both C-X-C
      and C-C chemokines are expressed in pulmonary-derived mast cells, suggesting an
      important contribution to leukocyte responses in the allergic airway.

PMID- 8558062
TI  - New members of the chemokine receptor gene family.
AB  - Chemokines are relatively small peptides with potent chemoattractant and
      activation activities for leukocytes. Several chemokine receptors have been
      cloned and characterized and all are members of the G protein-coupled receptor
      superfamily. Using degenerate oligonucleotides and polymerase chain reaction, we
      have identified seven novel receptors. Two of these sequences are presented here
      for the first time. We have shown, with gene mapping studies, that receptors with
      the highest sequence similarity are closely linked on human chromosomes. This
      close genetic association suggests a functional relationship as well.

PMID- 8558063
TI  - Expression and regulation of chemokines in bacterial pneumonia.
AB  - Effective host defense against bacterial invasion is characterized by the
      vigorous recruitment and activation of inflammatory cells which is dependent on
      the coordinated expression of both pro and anti-inflammatory cytokines. In this
      review, we present evidence indicating that both C-X-C and C-C chemokines are
      integral components of antibacterial host defense. Specifically, in vitro studies
      indicate that C-X-C chemokines [interleukin-8 (IL-8) and macrophage inflammatory
      protein 2 (MIP-2) and the C-C chemokine macrophage inflammatory protein 1 alpha
      (MIP-1 alpha) augment the ability of polymorphonuclear leukocytes (PMNs) and
      alveolar macrophages, respectively, to phagocytose and kill Escherichia coli. In
      addition, the intratracheal instillation of Klebsiella pneumoniae in CD-1 mice
      results in time-dependent production of MIP-2 and MIP-1 alpha and the inhibition
      of MIP-2 bioactivity in vivo results in decreases in lung PMN influx, impaired
      bacterial clearance, and early mortality. Finally, the anti-inflammatory cytokine
      interleukin-10 (IL-10) is also expressed within the lung during the evolution of
      Klebsiella pneumonia, and neutralization of IL-10 in vivo results in enhanced
      proinflammatory cytokine production, bacterial clearance, and increases in both
      short- and long-term survival. In conclusion, our studies indicate that specific
      chemokines are important mediators of leukocyte recruitment and/or activation in
      bacterial pneumonia and that the expression of these chemokines is regulated by
      endogenously produced IL-10.

PMID- 8558065
TI  - Some aspects of IL-8 pathophysiology. III: Chemokine interaction with endothelial
      cells.
AB  - Chemokines have been convincingly implicated in driving leukocyte emigration in
      different inflammatory reactions. However, the cellular and molecular mechanisms
      of chemokine involvement in leukocyte emigration are not clear. We and others
      suggested that leukocyte adhesion to the endothelium and transmigration are
      induced by chemokines immobilized on the endothelial cell surface. This would
      require the presence of specific chemokine binding sites in this microanatomical
      location. Using an in situ binding assay we demonstrated the presence of binding
      sites for interleukin-8 (IL-8) and RANTES, but not monocyte inflammatory protein
      1 alpha on the endothelium of postcapillary venules and small veins in human
      skin. In contrast, venules and veins in various anatomical locations showed
      dramatically differing IL-8 binding patterns. The subcellular distribution of IL
      8 in the venular endothelial cells following its in vivo and ex vivo injections
      was studied by use of electron microscopy. Our results suggest that IL-8 was
      internalized by the endothelial cells, transported transcellularly via
      plasmalemmal vesicles, and released onto the luminal surface where it appeared
      located preferentially on tips of membrane protrusions. We were unable to study
      the endothelial IL-8 binding or transport in vitro because all the in vitro
      propagated endothelial cell lines and primary endothelial cells tested lacked IL
      8 binding sites. This includes human umbilical vein endothelial cells (HUVECs),
      which also did not bind IL-8 in situ. However, HUVECs provided a satisfactory in
      vitro system to study the secretion of IL-8 by the endothelial cells. Two
      possible alternative pathways were described: secretion directly from the Golgi
      apparatus or following storage in Weibel-Palade bodies.

PMID- 8558064
TI  - The Duffy antigen receptor for chemokines: structural analysis and expression in
      the brain.
AB  - The Duffy antigen receptor for chemokines (DARC) is expressed in human
      erythrocytes and on endothelial cells lining postcapillary venules in kidney and
      spleen. DARC is a promiscuous chemokine receptor and a binding protein for the
      malarial parasite Plasmodium vivax. The expression of DARC by subsets of
      endothelial cells and neurons in discrete anatomic sites in the brain suggests
      that this enigmatic receptor may have multiple roles in normal and pathological
      physiology. Conservation of this promiscuous chemokine binding function is
      evident from the similarity in nucleotide sequence of DARC homologues from
      multiple species, as well as the high-affinity binding of human chemokines to
      murine and avian erythrocytes. Analysis of the functional domains of DARC using
      chimeric receptors and and monoclonal antibodies to multiple extracellular
      domains localized chemokine binding to structures in the amino terminal
      extracellular domain (E1). Scatchard analysis demonstrated that a chimeric DARC
      receptor, composed of the E1 domain of DARC and the predicted hydrophobic helices
      and loops of interleukin-8RB (IL-8RB), bound IL-8, and MGSA with KD values almost
      identical to the wild type receptors and bound a repertoire of C-X-C and C-C
      chemokines characteristic of DARC. Although numerous reports have demonstrated
      that chemokines such as IL-8 are expressed in the brain, presumably by glial
      cells, little insight into the nature of their role in normal or pathological
      physiology in the nervous system has developed because the target cells that
      express the corresponding receptors have not yet been identified. Northern
      blotting experiments suggest that mRNA encoding DARC are expressed in the central
      nervous system, however, interpretation of this is unclear because of the
      ubiquitous expression of DARC lining postcapillary venules. This study provides
      direct evidence to localize expression of DARC in the central nervous system.
      Immunohistochemical examination of human archival sections of the brain with
      monoclonal antibodies specific for DARC localize expression of DARC to cell
      bodies and processes of Purkinjie cells in the cerebellum. The
      immunohistochemical findings were supported by analysis of chemokine binding and
      radioligand crosslinking with membranes made from various brain fractions. The
      hierarchical expression of DARC in neurons in the cerebellum suggest that
      chemokines may play an important role in the modulation of neuronal activity by
      glial cells.

PMID- 8558066
TI  - Genetic approaches to study chemokine function.
AB  - Chemokines are cytokines capable of inducing chemotaxis of inflammatory cells in
      vitro. It is likely that they are also involved in controlling cell migration in
      vivo, but this and other putative functions have not been properly validated to
      date. To investigate these functions in vivo, a number of new experimental
      approaches are required. This mini-review focuses on a set of genetic approaches
      that can be used to understand chemokine function at the level of the organism.
      Hopefully, these approaches will help us define the fundamental role of
      chemokines in development, homeostasis, and disease.

PMID- 8558067
TI  - Selectivity and antagonism of chemokine receptors.
AB  - The chemokine superfamily can be subdivided into two groups based on their amino
      terminal cysteine spacing. The CXC chemokines are primarily involved in
      neutrophil-mediated inflammation and, so far, two human receptors have been
      cloned. The CC chemokines tend to be involved in chronic inflammation, and
      recently we have cloned a fourth leukocyte receptor for this group of ligands.
      Understanding what makes one receptor bind its range of agonists is important if
      we are to develop potent selective antagonist. We have started to investigate the
      molecular basis of this receptor selectivity by looking at why CC chemokines do
      not bind to the CXC receptors in several ways. First, we looked at the role of
      the three-dimensional structure of the ligand, and have solved the three
      dimensional structure of RANTES using nuclear magnetic resonance spectroscopy.
      The structure is similar to that already determined for the CC chemokine
      macrophage inflammatory protein-1 beta, and it has a completely different dimer
      interface to that of the CXC chemokine interleukin-8 (IL-8). However, the monomer
      structures of all the chemokines are very similar, and at physiological
      concentrations the proteins are likely to be monomeric. Second, by examining all
      the known CC and CXC chemokines, we have found a region that differs between the
      two subfamilies. Mutations of one of the residues in this region, Leu-25 in IL-8,
      to tyrosine (which is conserved at this position in CC chemokines) enables the
      mutant IL-8 to bind CC chemokine receptor-1 (CC-CKR-1) and introduces monocyte
      chemoattractant activity. Using other mutations in this region, we can show a
      direct interaction with the N-terminus of CC-CKR-1. Third, we have found that
      modification of the amino terminus of RANTES by addition of one amino acid makes
      it into an antagonist with nanomolar potency. Taken together, this data suggests
      a two-site model for receptor activation and for selectivity between CC and CXC
      chemokines, with an initial receptor contact provided by the main body of the
      chemokine, and activation provided by the amino terminal region.

PMID- 8558068
TI  - The role of chemokines in inflammatory joint disease.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by the
      elicitation and activation of a number of leukocyte populations within both the
      synovial space and joint tissue. The recruited leukocytes subsequently play an
      instrumental role in synovial cell proliferation, pannus formation, and bone
      erosion. Although it is know that leukocytes are important participants in the
      evolving joint pathology, the mechanism responsible for the successful
      elicitation of cells to the joint is not clear. A number of studies have
      identified an association of specific cytokines, including chemokines, with
      active arthritis, but longitudinal analyses of cytokine expression and the causal
      role of these mediators have not been defined. Animal models and cell culture
      systems have proved useful in identifying the expression of various cytokines
      during the maintenance of chronic joint inflammation. In addition, animal models
      have provided important information regarding the kinetic production and
      contribution of specific mediators to the development of experimental arthritis.
      These studies provide insights into the potential mechanisms for leukocyte
      involvement in inflammatory joint disease.

PMID- 8558069
TI  - The role of MIP-1 alpha in inflammation and hematopoiesis.
AB  - Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a member of the C-C
      subfamily of chemokines, a large superfamily of low-molecular weight, inducible
      proteins that exhibit a variety of proinflammatory activities in vitro including
      leukocyte chemotaxis. MIP-1 alpha is a particularly interesting chemokine,
      because in addition to its proinflammatory activities, it inhibits the
      proliferation of hematopoietic stem cells in vitro and in vivo. Here, the
      biologic properties of MIP-1 alpha are reviewed in light of recent data on mice
      homozygous for a disruption of the MIP-1 alpha gene. The MIP-1 alpha null mice
      have no overt abnormalities of peripheral blood or bone marrow cells, indicating
      that MIP-1 alpha is not necessary for normal hematopoiesis. However, the MIP-1
      alpha null mice have a mice have a reduced inflammatory reduced inflammatory
      response to influenza virus and are resistant to coxsackievirus-induced
      myocarditis. These data demonstrate that MIP-1 alpha is required for a normal
      inflammatory response to these viruses. Agent that inhibit the action of MIP-1
      alpha may therefore prove useful for controlling inflammation in these and other
      settings.

PMID- 8558070
TI  - Human monocyte chemotactic proteins-2 and -3: structural and functional
      comparison with MCP-1.
AB  - Structurally, the monocyte chemotactic proteins MCP-1, -2, and -3 form a
      subfamily of the C-C or beta-chemokines. Like other chemokines, MCPs are produced
      by a variety of cells on stimulation with cytokines (interleukin-1, tumor
      necrosis factor-alpha, interferon-gamma), bacterial and viral products or
      mitogens. MCP-1 levels are enhanced during infection and inflammation, which are
      characterized by leukocyte infiltration. In vitro, MCPs are chemotactic for a
      distinct spectrum of target cells and show different specific biological
      activities depending on the cell type and the chemokine tested. MCP-3 has the
      broadest range in that it activates monocytes, dendritic cells, lymphocytes,
      natural killer cells, eosinophils, basophils, and neutrophils. The most sensitive
      cells to all three MCPs are lymphocytes and monocytes. MCP-1 is a potent basophil
      activator but does not attract eosinophils, whereas, at higher concentrations,
      MCP-2 also stimulates both eosinophils and basophils. The signal transduction of
      MCPs on monocytes involves at least two G protein-linked C-C chemokine receptors:
      C-C CKR-1 binds MCP-3 and C-C CKR-2 binds MCP-1 and MCP-3 but not MCP-2. Receptor
      binding leads to enhanced [Ca2+]i for all chemokines except for MCP-2.

PMID- 8558071
TI  - Regulation and expression of chemokines: potential role in glomerulonephritis.
AB  - Glomerular disease represent the major cause of renal failure. Despite decades of
      research or understanding of the mechanism(s) associated with immune-mediated
      glomerular injury remains poor. Consequently most of the therapies that are used
      are nonspecific with major side effects and offer minimal therapeutic benefits
      for the patient. The need for new strategies for therapy is clear. The drawing of
      leukocytes from the circulation into the inflamed glomerulus, accompanied by
      proliferation of resident mesangial cells and expansion of the mesangial matrix
      are key processes in the pathogenesis of glomerulonephritis (GN). The migration
      of inflammatory cells into an extravascular site requires a series of coordinated
      signals including the generation of a chemotactic gradient by the cells of
      extravascular compartment. The nature of the stimulus and the subsequent spectrum
      of chemotactic factors produced determine the specific leukocyte population
      recruited to the inflammatory site. Members of the chemokine family play a
      central role in this process by attracting and stimulating specific subsets of
      leukocytes. Our hypothesis is that mesangial cell-derived chemokines are
      responsible for the initiation and maintenance of glomerular inflammation; in
      this review we discuss our recent findings supporting this theory. Increasing our
      understanding of the intracellular pathway that regulate chemokine production in
      human mesangial cells may provide leads to the design of more effective therapies
      for the prevention and treatment of glomerular inflammation.

PMID- 8558072
TI  - Beta chemokines costimulate lymphocyte cytolysis, proliferation, and lymphokine
      production.
AB  - We report here the ability of the beta chemokines MIP-1 alpha, MIP-1 beta,
      RANTES, and MCP-1 to enhance some lymphocyte effector functions. Initial studies
      focused on the effects of chemokines on human and mouse cytotoxic T lymphocyte
      (CTL)- and natural killer (NK) cell-specific cytolytic responses. The results
      demonstrate that beta chemokines are capable of augmenting mouse and human CTL
      and human NK- but not lymphokine-activated killer cell- or antibody-dependent
      cell cytotoxicity-specific cytolytic responses. Neutralization analysis utilizing
      integrin-specific antibodies revealed that CTL/NK tumor cell conjugate formation
      is required for chemokine-induced killing. In addition, both CTLs and NK cells
      incubated with various beta chemokines were induced to degranulate and release
      granule-derived serine esterases, suggesting that chemokines may be important
      costimulators of CTL and NK cell degranulation and may thus augment local target
      cell destruction. Chemokines also modulate antigen-driven T cell proliferative
      responses as well as effects on lymphokine production. Many of the beta
      chemokines were found to potentiate human and mouse antigen-specific Th1 and Th2
      clone activation promoting cellular proliferation and the release of various
      lymphokines. This chemokine-mediated T cell proliferation was chemokine and
      antigen dose dependent as well as clone dependent. Chemokine pretreatment
      analyses with T cells and antigen-presenting cells (APCs) revealed that
      chemokines up-regulate both T cells and antigen- presenting cells (APCs) revealed
      that chemokines up-regulate both T cell and APC functions. Costimulation assays
      using immobilized antiCD3 monoclonal antibody-coated plates and purified human
      and mouse T cells and T cell clones in the presence of various chemokines also
      exhibited enhanced proliferation and lymphokine secretion. This costimulation was
      interleukin-2 dependent and required the presence of free extracellular calcium.
      Examination of chemokine-treated APCs revealed that the T cell costimulatory
      molecule B7-1 was induced by various beta chemokines. Neutralization of
      endogenously produced chemokines, with specific antibodies during an antigen
      specific T cell response blocked cellular proliferation, suggesting that the
      chemokines have an autocrine role in antigen-induced T cell proliferative
      responses. Together, these results suggest that chemokines play a significant
      role in the activation of polyclonal as well as antigen-specific helper and
      cytotoxic T cells during the genesis of an immune response.

PMID- 8558073
TI  - Effects of dexamethasone on bovine circulating T lymphocyte populations.
AB  - In cattle, gamma delta T cells represent a higher proportion of circulating T
      cells than in humans. Bovine gamma delta T cells can be recognized by expression
      of gamma delta cell receptor (gamma delta TCR) determinants or by a 215/230-kDa
      surface antigen (WC1). WC1 is expressed on 90% or more of circulating bovine
      gamma delta T cells. The effects of dexamethasone on this and other subsets (CD3,
      CD2, CD4, CD8) of peripheral blood T lymphocytes were determined by flow
      cytometric analysis. Twelve 15-month old bulls were injected with dexamethasone
      (0.04 mg/kg/day) for 3 consecutive days and four bulls were untreated controls.
      Blood samples were collected daily for 3 days before dexamethasone injections and
      for an additional 7 days starting on the third day. Data were recorded as percent
      positive cells and as mean fluorescent intensity (MFI) of positive cells.
      Initially, CD3+ cells represented 65-73% of all peripheral blood clear cells
      (PBMC). Dexamethasone reduced CD3+/- cells (PBMC). Dexamethasone reduced CD3+
      cells to 30% and these recovered to 50% positive cells by 9 days after the last
      dexamethasone injection. Loss of CD3+ cells was not due to reductions in alpha
      beta T cells because dexamethasone did not influence the percent CD2+, CD4+, or
      CD8+ cells. However, percent WC1+ cells rapidly declined from a baseline of 26.4%
      of PBMC to < 6% by the final injection. During injections, the MFI of WC1
      increased. The MFI of WC1 returned to control values 7 days after the last
      injection of dexamethasone, but the percent gamma delta T cells recovered to only
      14% WC1+ PBMC by the final day of the study. During its maximum effects on WC1,
      dexamethasone also caused a profound decrease of L-selectin MFI on remaining PBMC
      (mostly alpha beta T cells and monocyte/macrophages). In a second trial, two
      color analyses determined that dexamethasone did not increase apoptosis in WC1+
      cells and did not reduce L-selectin MFI on either CD2+ of WC1+ cells. The
      cumulative results suggested that dexamethasone promoted gamma delta T cell
      migration out of peripheral blood via an L-selectin-independent mechanism and
      that dexamethasone did not alter alpha beta T cell migration kinetics.

PMID- 8558074
TI  - Lipoprotein receptor interactions are not required for monocyte oxidation of LDL.
AB  - Upon activation, human peripheral blood monocytes and U937 cells oxidized low
      density lipoprotein (LDL), converting it to a cytotoxin. The oxidized LDL loses
      its ability to interact specifically with the native LDL (apoB/E) receptor and
      becomes a ligand for the scavenger receptors and two other receptors, Fc gamma
      RII (CD32) and CD36. We performed a series of studies to evaluate the potential
      contribution of each of these receptors to the process of monocyte-mediated LDL
      oxidation. To assess the participation of the apoB/E receptor, we tested the
      ability of activated human monocytes to oxidize LDL after up- and down-regulation
      of apoB/E receptors. Neither up-regulation nor down-regulation of the apoB/E
      receptor significantly modified the level of LDL lipid oxidation. Acetylated LDL,
      a ligand for scavenger receptors, was also oxidized by the activated monocytes.
      Methylated LDL, a chemically modified LDL that is not recognized by the apoB/E or
      scavenger receptors, was oxidized as well. Thus, LDL does not need to interact
      with either the apoB/E receptor or scavenger receptors in order to undergo lipid
      oxidation. Additionally, monoclonal antibodies to CD36 and CD32 were used to
      block these two receptors that recognize oxidized LDL. Although both antibodies
      interfered with oxidized LDL binding to these receptors, neither treatment
      interfered with LDL lipid oxidation mediated by activated human monocytes. Our
      results suggest that interaction with these receptors is not a requirement for
      LDL lipid oxidation by activated human monocytes.

PMID- 8558075
TI  - Animal cell mutants unable to take up biologically active glycerophospholipids.
AB  - We have isolated two mutant strains from the murine, macrophage-like cell line,
      RAW 264.7, that are resistant to the cytotoxic effects of the antineoplastic,
      platelet activating factor analogue, 1-octadecyl-2-methyl-rac-glycero-3
      phosphocholine (ET-18-OMe). The mutants were isolated using a single round of
      selection to ensure that resistance was due to a single gene defect. These
      mutants, RAW.R1 and RAW.R23, are approximately 20 times more resistant to ET-18
      OMe (ID50 = 15-17 microM) than the parent strain (ID50 = 0.7-1.0 microM).
      Resistance to ET-18-OMe was due to a 90-95% reduction in the ability to take up
      and accumulate this compound. The uptake of other choline glycerophospholipids
      (e.g., platelet activating factor and 1-acyl-2-lyso-sn-glycero-3-phosphocholine)
      was also severely affected. This defect was not limited to choline
      glycerophospholipids; the uptake of an ethanolamine glycerophospholipid (1-alkyl
      2-lyso-sn-glycero-3-phosphoethanolamine) was reduced by 80%. The uptake of
      palmitic acid, an amphipathic molecule bearing no phosphate-containing head
      group, was unaffected in the mutants. There was little metabolism of ET-18-OMe by
      either the wild-type or mutant cells. Binding of ET-18-OMe appeared to be normal
      in the mutants, but internalization of pre-bound ET-18-OMe was reduced. Uptake of
      non-lipid ligands such as horseradish peroxidase, lucifer yellow, and transferrin
      was normal in the mutants demonstrating that fluid-phase and receptor-mediated
      endocytosis is functional. The ability to generate mutants displaying a lesion
      that affects the uptake of both choline and ethanolamine phospholipids
      demonstrates that these species are internalized by RAW cells through one common
      primary route or through pathways that share a common factor. These mutants, and
      this approach to their isolation, offer a system with which to study and define
      the mechanisms of glycerophospholipid uptake into macrophages as well as other
      cell types.

PMID- 8558076
TI  - Lipid ester-bound aldehydes among copper-catalyzed peroxidation products of human
      plasma lipoproteins.
AB  - We have isolated the core aldehydes (aldehydes still bound to parent molecules)
      of phosphatidylcholine (PC) and cholesteryl esters (CE) from copper-catalyzed
      peroxidation of human plasma low (LDL) and high (HDL) density lipoproteins. The
      aldehydes were isolated by extraction with acidified chloroform-methanol
      containing 2,4-dinitrophenylhydrazine. The 2,4-dinitrophenylhydrazone (DNPH)
      derivatives formed were resolved by reversed phase high performance liquid
      chromatography (HPLC) and identified by on-line quadrupole mass spectrometry
      (LC/MS). The major PC core aldehydes from oxidized LDL and HDL were identified as
      1-palmitoyl-(1-stearoyl) 2-(9-oxononanoyl)-, 1-palmitoyl-(1-stearoyl) 2-(8
      oxooctanoyl)-, and 1-palmitoyl-(1-stearoyl) 2-(5-oxovaleroyl)-sn-glycerols after
      phospholipase C digestion of the DNPH derivatives of the phospholipids. The major
      aldehydes from peroxidation of cholesteryl esters were the 9-oxononanoyl, 8
      oxooctanoyl, and 5-oxovaleroyl esters of cholesterol and 7-ketocholesterol. The
      core aldehydes were estimated to account for a minimum of 1-2% of the consumed
      linoleate and arachidonate esters. A relatively smaller yield of the PC core
      aldehydes from LDL compared to HDL was attributed to the presence of greater
      amounts of phospholipases in LDL than in HDL. More comparable yields of PC core
      aldehydes were obtained in the presence of phenylmethylsulfonylfluoride, which
      inhibits phospholipases. We conclude that peroxidation of LDL and HDL results in
      formation of detectable amounts of cholesteryl and glycerophospholipid esters
      containing aldehyde functions. The yield of PC aldehydes varies with the activity
      of the platelet activating factor (PAF) acetyl hydrolase.

PMID- 8558077
TI  - Efflux of intracellular versus plasma membrane cholesterol in HepG2 cells:
      different availability and regulation by apolipoprotein A-I.
AB  - We have compared the efflux of cholesterol from different cellular pools of human
      hepatoma cells HepG2 using intact cells or isolated membrane fractions. To label
      different pools, cells were incubated with either unesterified [14C]cholesterol
      that had been incorporated into high density lipoproteins ([14C]FC-HDL), low
      density lipoproteins ([14C]FC-LDL), or phosphatidylcholine liposomes ([14C]FC
      PC), or with [14C]acetate. Cell fractionation revealed that labeling of cells
      with [14C]FC-PC resulted in the incorporation of [14C]cholesterol almost
      exclusively into the plasma membrane (PM), while incubation with [14C]FC-HDL
      resulted in the majority of [14C]cholesterol incorporation into the PM, but with
      a smaller component associated with lysosomes. Labeling with [14C]FC-LDL or
      [14C]acetate led to an accumulation of [14C]cholesterol predominantly in
      lysosomes or the endoplasmic reticulum (ER), respectively. When the kinetics of
      [14C]cholesterol efflux was analyzed after pulse-labeling of different cellular
      pools, half-times of cholesterol efflux from lysosomes and ER were significantly
      longer than that from PM. In another set of experiments, when both labeling and
      efflux times varied, efflux of [14C]cholesterol from the PM to human serum after
      1.5 h pulse and chase incubations was double that from lysosomes and 8-fold that
      from ER. Extension of the incubation times from 1.5 to 3 h diminished the
      difference in cholesterol efflux from different membranes. Further incubation to
      6 h almost abolished the different responses. Cell-free preparations of
      membranes, obtained from cells labeled with [14C]cholesterol, showed no
      differences in cholesterol efflux. No differences in the distribution of
      [14C]cholesterol released into serum among lipoprotein subfractions was observed.
      Pretreatment of the serum with Fab fragments of polyclonal rabbit anti-human
      apolipoprotein A-I antibodies reduced its ability to promote efflux of
      cholesterol from the ER by 77%, but had no effect on cholesterol efflux from the
      PM. Fab fragments of non-immune IgG had no effect on the efflux of both ER and PM
      cholesterol. We conclude that the availability of cellular cholesterol for efflux
      from HepG2 cells is strongly influenced by its subcellular location, and is
      regulated by apolipoprotein A-I.

PMID- 8558078
TI  - Metabolism of deuterium-labeled linoleic, 6,9,12-octadecatrienoic, 8,11,14
      eicosatrienoic, and arachidonic acids in the rat.
AB  - Male weanling rats were fed a diet that contained 2.1% ethyl oleate, 1% ethyl
      linoleate, and 0.2% ethyl linolenate. After 4 weeks all the linoleate was
      replaced by the deuterium-labeled analog and the animals were killed 4 days
      later. The molar fraction of total 20:4(n-6) in liver, heart, and kidney
      phospholipids containing deuterium was 33.9, 8.9, and 13.3%, respectively.
      Second, animals were preconditioned by incorporating either 0.2% of 18:3(n-6),
      20:3(n-6), or 20:4(n-6) into the above diet and again after 4 weeks all the
      linoleate was replaced with the labeled analog. Now the molar fraction of labeled
      20:4(n-6) in liver phospholipids from these three groups of animals was reduced
      from 33.9 to 27.1, 23.9, and 24.1% respectively. In contrast, there was little
      change in the specific activity of 20:4(n-6) in heart and kidney phospholipids.
      The third protocol was a direct crossover study in that again unlabeled linoleate
      was fed during the entire period. Four days prior to killing the unlabeled 18:3(n
      6), 20:3(n-6), and 20:4(n-6) were replaced with the deuterium-labeled analogs.
      The mole % of total esterified 20:4(n-6) in liver phospholipids was now 24.6,
      32.0, and 26.2%, respectively. Even though 18:3(n-6), 20:3(n-6), and 20:4(n-6)
      were all fed at only 20% of the level of 18:2(n-6), it can be calculated that the
      molar fraction of esterified 20:4(n-6) in liver phospholipids was between 65 to
      77% of that found when 18:2(n-6) was the only dietary (n-6) acid as under these
      conditions 33.9 mol % of the 20:4(n-6) was labeled. Interestingly, when deuterium
      labeled 18:3(n-6), 20:3(n-6), or 20:4(n-6) was fed, the specific activity of
      esterified 20:4(n-6) in kidney and heart phospholipids was always equal to or
      greater than what was derived from deuterium-labeled 18:2(n-6). The results show
      that under steady-state dietary conditions, (n-6) dietary fatty acids are
      processed in different ways by liver, heart, and kidney.

PMID- 8558079
TI  - Molecular characterization of two monoclonal antibodies specific for the LDL
      receptor-binding site of human apolipoprotein E.
AB  - Apolipoprotein E (apoE), a 299 amino acid protein, is a ligand for the low
      density lipoprotein receptor (LDLr). It has been established that basic amino
      acids situated between apoE residues 136 and 150 participate in the interaction
      of apoE with the LDLr. Evidence suggests that apoE is heterogeneous on
      lipoproteins in its conformation and in its ability to react with cell surface
      receptors. Our goal was to produce mAbs that could serve as conformational probes
      of the LDLr binding site of apoE. We used a series of apoE variants that have
      amino acid substitutions at residues 136, 140, 143, 144, 145, 150, 152, and 158
      to identify the epitopes of two anti-human apoE monoclonal antibodies (mAbs), 1D7
      and 2E8, that inhibit apoE-mediated binding to the LDLr. We show that most of the
      variants that have reduced reactivity with the LDL receptor also have reduced
      reactivity with the mAbs. The epitopes for both mAbs appear to include residues
      143 through 150 and thus coincide with the LDLr-binding site of apoE. It is
      notable that mAb 2E8, but not 1D7, resembles the LDLr in showing a reduced
      reactivity with apoE (Arg158 --> Cys). While most of the receptor-defective
      variants involve replacement of apoE residues directly implicated in binding,
      substitution of Arg158 by Cys is thought to indirectly affect binding of apoE to
      the LDLr by altering the conformation of the receptor-binding site. To determine
      whether the similarity in specificities of the mAbs and the LDLr reflect
      structural similarities, we cloned and characterized the cDNAs encoding the light
      and heavy chains of both mAbs. Primary sequence analysis revealed that, although
      these two antibodies react with overlapping epitopes, their respective
      complementarity determining regions (CDRs) share little homology, especially
      those of their heavy chains. The two mAbs, therefore, likely recognize different
      epitopes or topologies within a limited surface of the apoE molecule. Four
      negatively charged amino acids were present in the second CDR of the 2E8 heavy
      chain that could be approximately aligned with acidic amino acids within the
      consensus sequence of the LDLr ligand-binding domain. This could indicate that
      mAb 2E8 and the LDLr use a common mode of interaction with apoE.

PMID- 8558080
TI  - Determination of mRNA levels of cholesterol biosynthesis enzymes and LDL receptor
      using ribonuclease protection assay.
AB  - We designed a rapid method for determining mRNA content of cholesterol
      biosynthesis enzymes and LDL receptor (LDLR) using a ribonuclease protection
      assay (RPA). 32P-labeled cRNA fragments for genes of human LDLR and the enzymes
      HMG-CoA synthase (HMGS), HMG-CoA reductase (HMGR), mevalonate kinase (MK),
      farnesyl pyrophosphate synthase (FPPS), and squalene synthase (SQS) were prepared
      by in vitro transcription. Total RNA prepared from HepG2 cells was hybridized
      with the cRNA probe and the hybridized mRNA was determined under protection from
      RNase digestion. Probe content used in this assay was excess in determining the
      desired mRNA in total RNA, and surplus probes were completely digested using
      RNase under standard conditions. When cells were cultured in DMEM supplemented
      with 10% fetal calf serum (FCS), mRNA levels of FPPS, SQS, and LDLR were about 4-
      to 7-fold higher than those of HMGS, HMGR, and MK. On incubation with DMEM
      supplemented with 10% lipoprotein-deficient serum (LPDS) for 8 h, all messenger
      RNA levels increased 1.5- to 3.5-fold. In addition, when the HMG-CoA reductase
      inhibitor compactin was added to 10% LPDS-DMEM, these levels increased even
      further and the change in mRNA level seemed to differ between the enzymes and
      LDLR. From these results, we conclude that RPA is a useful method for determining
      the very small amount of mRNA level of cholesterol biosynthesis enzymes and LDLR
      in the cell.

PMID- 8558081
TI  - Extracellular processing of phospholipids is required for permeability barrier
      homeostasis.
AB  - Three key lipid types, cholesterol, ceramides (CER), and free fatty acids (FA),
      form the stratum corneum (SC) lamellar bilayers that mediate barrier function.
      Prior studies have shown that barrier requirements regulate CER generation from
      glucosylCER, and that this catabolic step takes place within the SC interstices.
      Here, we addressed whether extracellular processing of phospholipids (PL), the FA
      precursor delivered to the SC interstices with glucosylCER and cholesterol during
      exocytosis of lamellar body contents, is also required for barrier homeostasis.
      We applied two chemically unrelated inhibitors of phospholipase A2 (PLA2-I), BPB
      (irreversible) and MJ33 (reversible), topically to hairless mice after barrier
      perturbation with acetone. Both inhibitors delayed barrier recovery at non
      cytotoxic doses, while MJ45, an analogue known to inhibit PLA2-II but not PLA2-I,
      had no effect. Moreover, the delays in barrier recovery induced by BPB and MJ33
      could be overridden by co-applications of palmitic acid, but not linoleic acid or
      lysolecithin. Furthermore, inhibitor-treatment resulted in accumulation of PL and
      depletion of FA in the SC by 4 h, as well as the persistence of "immature"
      lamellar body-derived membrane structures in the SC interstices. Finally, these
      changes in membrane structure were reversed when inhibitor-treated SC was
      incubated in vitro with palmitic acid. These studies show that: 1) inhibition of
      PLA2 results in abnormalities in lipid composition and SC structure that alter
      barrier homeostasis; and 2) the functional defect can be attributed to a
      deficiency of nonessential FA within the SC. Thus, extracellular processing of PL
      into FA is required for normal barrier function.

PMID- 8558082
TI  - Structural and thermotropic properties of synthetic C16:0 (palmitoyl) ceramide:
      effect of hydration.
AB  - Differential scanning calorimetry (DSC) and X-ray diffraction techniques have
      been used to investigate the structure and thermotropic properties of synthetic,
      non-hydroxy fatty acid (16:0) ceramide (NFA(C16)CER) as a function of hydration.
      Anhydrous NFA(C16)CER shows a single, broad endothermic transition at 95.4
      degrees C (delta H = 10.4 kcal/mol). On hydration, a broad exothermic transition
      appears at approximately 50-70 degrees C while the main endothermic transition
      decreases to 90.0 degrees C (delta H = 13.8 kcal/mol). The enthalpy of the
      exothermic transition increases with hydration to a maximum value, delta H = 4.8
      kcal/mol. This polymorphic phase behavior depends on the low temperature
      incubation time and prior cooling rate. X-ray diffraction of fully hydrated
      NFA(C16)CER at 26 degrees C, shows a well-ordered lamellar phase with a bilayer
      periodicity d = 46.9 A. At 68 degrees C, above the first exothermic transition, X
      ray diffraction shows again a lamellar phase with reduced bilayer periodicity d =
      41.8 A and an increased number of both lamellar and wide-angle reflections
      indicative of enhanced layer and chain packing order, respectively. At 90.0
      degrees C, above the main transition, the diffraction pattern shows a broad,
      intense reflection at 29.9 A and a diffuse reflection at 4.6 A, indicative of a
      melted chain phase. On cooling, NFA(C16)CER exhibits polymorphic phase behavior
      involving the conversion of the melted chain phase to a metastable bilayer phase.
      On heating, this metastable phase undergoes an exothermic transition to a stable
      bilayer phase; on further heating, NFA(C16)CER converts endothermically to the
      melted-chain phase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8558083
TI  - Physical properties of ceramides: effect of fatty acid hydroxylation.
AB  - The structural and thermotropic properties of alpha-hydroxy fatty acid (HFA) and
      non-hydroxy fatty acid (NFA) ceramides (CER) have been studied using differential
      scanning calorimetry (DSC) and X-ray diffraction techniques. The DSC of anhydrous
      HFA-CER shows a single, sharp reversible transition at 95.6 degrees C (delta H =
      15.3 kcal/mol). At intermediate hydrations HFA-CER exhibited more complex
      behavior but at maximum hydration only a single reversible transition is observed
      at 80.0 degrees C (delta H = 8.5 kcal/mol). X-ray diffraction of hydrated (74%
      water) HFA-CER at 20 degrees C shows a lamellar structure with a bilayer
      periodicity d = 60.7 Angstrum; a single wide angle reflection at 4.2 Angstrum is
      characteristic of hexagonal chain packing. Above the main transition temperature
      at 91 degrees C, a hexagonal (HII) phase is observed. In contrast, DSC of
      anhydrous NFA-CER demonstrates two thermal transitions at 81.3 degrees C (delta H
      = 6.8 kcal/mol) and 85.9 degrees C (delta H = 3.5 kcal/mol). With increasing
      hydration, both transitions shift towards lower temperatures; at maximum
      hydration, on heating, the endothermic transitions occur at 72.7 degrees C (delta
      H = 9.8 kcal/mol) and 81.1 degrees C (delta H = 4.0 kcal/mol). On cooling, there
      is hysteresis of both transitions. X-ray diffraction of NFA-CER (80% water) at 20
      degrees C shows a well-ordered lamellar structure with a bilayer periodicity d =
      58.6 Angstrum and three wide-angle reflections at 4.6 Angstrum, 4.2 Angstrum, and
      3.8 Angstrum. At 77 degrees C (between the two transitions), again a lamellar
      structure exists with reduced bilayer periodicity d = 53.1 Angstrum and four wide
      angle reflections at 4.6 Angstrum, 4.2 Angstrum, and 3.8 Angstrum are observed.
      Above the second transition, only a single low angle reflection at 30.0 Angstrum
      is observed; a diffuse reflection at 4.6 Angstrum is indicative of a melted chain
      phase. Thus, HFA-CER exhibits a simple phase behavior involving the reversible
      conversion of a gel phase to a hexagonal phase (L beta-->HII). However, NFA-CER
      shows a more complex polymorphic phase behavior involving two gel phases.

PMID- 8558084
TI  - Lipolysis-induced partitioning of free fatty acids to lipoproteins: effect on the
      biological properties of free fatty acids.
AB  - Free fatty acids (FFA) released during the lipolysis of triglyceride (TG)-rich
      lipoproteins in vivo are generally believed to be bound to serum albumin. When
      hypertriglyceridemic (HTG) sera were lipolyzed in vitro by purified bovine milk
      lipoprotein lipase (LpL), there was an 11- to 18-fold increase in serum FFA
      levels, and a major portion (> 80%) of the FFA in serum was partitioned to
      lipoprotein fractions. The greatest portion (33%) of FFA in lipolyzed HTG serum
      was associated with newly formed flocculent remnants that banded just below low
      density lipoproteins (LDL) in the density gradient tube. Very low density
      lipoprotein (VLDL), LDL, and high density lipoprotein (HDL) fractions in
      lipolyzed HTG serum contained 18- to 29-times more FFA molecules than those in
      prelipolysis serum. Analysis of the fatty acyl chain composition of FFA in
      lipolyzed HTG serum showed that the extent of partitioning of saturated FFA into
      the lipoprotein fractions relative to that of polyunsaturated FFA was about 4.5-
      to 11-times greater than that partitioned into the free protein fraction; most
      (84%) of FFA partitioned into flocculent remnants were saturated fatty acids. In
      vivo lipolysis of TG-rich lipoproteins in HTG subjects, induced by
      heparinization, resulted in only a small (2.8-fold) increase in serum FFA and
      little or no increase in the partitioning of FFA to lipoproteins. However, in
      vitro incubation of the postheparin serum at 37 degrees C for 90 min resulted in
      a 2.9- to 6.8-fold increase in the serum FFA level and the partitioning of > 66%
      of total serum FFA into lipoprotein fractions. Studies of the interaction of
      various plasma fractions from control and in vitro lipolyzed HTG serum with
      cultured mouse peritoneal macrophages (MPM) showed that FFA partitioned to
      lipoprotein fractions were highly cytotoxic to cultured MPM, whereas FFA
      partitioned to albumin at a 10 x greater concentration were not cytotoxic. The
      cytotoxic potencies of FFA bound to lipoproteins and albumin were further
      compared after in vitro incorporation of FFA (oleic acids) into LDL and to
      albumin. FFA bound to LDL but not to albumin were cytotoxic to cultured MPM; the
      cytotoxicity of FFA bound to LDL was more closely related to the FFA to LDL
      cholesterol molar ratio than to the total FFA concentration in the culture dish.
      The ability of FFA bound to LDL and albumin to induce foam cell formation was
      studied in THP-1 monocyte-derived macrophages, which were less susceptible to
      cytotoxicity produced by FFA bound to LDL than MPM.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8558085
TI  - Characterization of endothelial cell injury by cholesterol oxidation products
      found in oxidized LDL.
AB  - The present study describes the toxicity of oxidized LDL towards rabbit aortic
      endothelial cells in terms of its lipid components with specific attention to the
      cholesterol oxidation products (ChOx) found in oxidized LDL isolated from human
      plasma. Measurements of the major ChOx associated with freshly isolated
      unmodified LDL, those found in oxidized LDL isolated from human plasma and LDL
      subjected to oxidation in vitro are described. We have confirmed previous
      findings that most of the cytotoxicity of freshly isolated human LDL may be
      attributable to a minor fraction that appears to be oxidatively modified by
      several criteria. Moreover, this plasma-derived oxidized LDL (referred to as LDL)
      is highly enriched in ChOx, whereas the content of lipid peroxides or derived
      products (measured as conjugated dienes and thiobarbituric acid reacting
      products) are much lower, particularly when compared to copper-induced LDL
      oxidation. Much of the ChOx found in plasma are associated with LDL, however, the
      levels and proportions of the various ChOx found in LDL differ from those
      produced after extensive copper-induced oxidation but resemble those produced
      after moderate oxidation with copper. The species and concentrations of ChOx
      found in LDL when applied as a mixture exhibit considerably more toxicity than
      any individual ChOx alone. At non-toxic levels this ChOx mixture causes an
      increased influx of several ions, including calcium, an effect not seen with
      individual ChOx at comparable doses. Perturbations in ionic homeostasis, and
      particularly the sustained increase in intracellular calcium concentrations, are
      associated with much of the cytotoxicity, an effect attributable to the membrane
      disruptive action of ChOx leading to altered ion transporter activity. The effect
      of the ChOx mixture (but not any individual ChOx) on sodium and potassium flux
      appears to be due to enhanced Na+/K(+)-ATPase activity based on the complete
      inhibition produced by ouabain under all treatment conditions. These findings
      also show that the levels of cholesterol oxidation products found in normal LDL
      are not cytotoxic whereas those present in oxidized LDL exceed the toxic
      threshold for endothelial cells and account for most of the cytotoxicity produced
      by this modified lipoprotein.

PMID- 8558086
TI  - Lipoteichoic acid stimulates lipolysis and hepatic triglyceride secretion in rats
      in vivo.
AB  - The host response to infection is frequently accompanied by changes in lipid
      metabolism. Previous studies have shown that endotoxin (LPS), a component of the
      cell wall of gram-negative bacteria, increases serum lipid levels. In this study,
      we demonstrate that lipoteichoic acid (LTA), a component of the cell membrane of
      gram-positive bacteria, also increases serum lipid levels in rats in a dose
      dependent manner (0.1-300 micrograms/200 g body weight). Serum triglyceride
      levels increased within 2 h after LTA administration with peak values at 4 h (2
      fold increase). Serum cholesterol levels also increased but the effect was
      delayed occurring at 16 h and was relatively small (1.2-fold increase). LTA (10
      micrograms/200 g BW) did not decrease adipose tissue lipoprotein lipase activity
      or the clearance of triglyceride-rich lipoproteins. Rather, the LTA-induced
      hypertriglyceridemia is due to an increase in hepatic triglyceride secretion. LTA
      stimulates both hepatic de novo fatty acid synthesis and lipolysis. The increased
      delivery of free fatty acids to the liver plays a major role in the LTA-induced
      hypertriglyceridemia. Pretreatment with phentolamine, an alpha-adrenergic
      receptor antagonist, and alprenolol, a beta-adrenergic receptor antagonist, or
      phentolamine alone significantly suppressed the hypertriglyceridemia induced by
      LTA. These adrenergic inhibitors had no significant effect on the increase in
      lipolysis. These results indicate that catecholamines are involved in mediating
      the LTA-induced increase in hepatic triglyceride secretion via alpha-adrenergic
      receptors. These changes in lipid metabolism may play an important role in the
      organism's response to gram-positive infection.

PMID- 8558087
TI  - Lipoperoxides in LDL incubated with fibroblasts that overexpress 15-lipoxygenase.
AB  - Oxidative modification of LDL plays an important role in early atherogenesis but
      the mechanisms, nonenzymatic and/or enzymatic, by which LDL is oxidized in vivo
      remain to be established. Several lines of evidence suggest that cellular 15
      lipoxygenase (arachidonate 15-oxidoreductase, EC.1.13.11.13) (15-LO) may
      contribute to oxidative modification of LDL, including recent studies
      demonstrating that murine fibroblasts overexpressing 15-LO have an enhanced
      capacity to oxidize LDL in the medium. The present studies were undertaken to
      better understand the mechanisms by which cells expressing 15-LO bring about
      oxidative modification of LDL. LDL incubated 1-2 h with the 15-LO-enriched cells
      showed a much higher lipoperoxide (LOOH) content than did LDL incubated with
      control cells. By far the largest absolute increase occurred in cholesteryl ester
      hydroperoxide (CE-OOH), a much lesser increase in free fatty acid hydroperoxides
      (FFA-OOH), and only a very small increase in phospholipid hydroperoxides (PL
      OOH). Addition of EDTA to the medium abolished these increases in LDL lipid
      hydroperoxides. Enrichment of LDL with probucol or vitamin E also prevented CE
      OOH accumulation. Incubation of LDL with linoleic acid hydroperoxide in the
      absence of cells also caused a significant increase in CE-OOH and this was
      markedly inhibited by EDTA. These findings provide further evidence for the
      potential of 15-LO to participate in LDL oxidation by way of a mechanism
      involving introduction of LOOH into the LDL particle followed by metal-catalyzed
      propagation.

PMID- 8558088
TI  - Oxidized low density lipoprotein-mediated activation of phospholipase D in smooth
      muscle cells: a possible role in cell proliferation and atherogenesis.
AB  - Low density lipoproteins (LDL) are risk factors in atherosclerosis and oxidative
      modification of LDL to oxidized LDL (OX-LDL) increases its atherogenicity.
      Development of atherosclerosis likely involves OX-LDL-mediated smooth muscle cell
      (SMC) proliferation. However, the mechanism(s) of SMC proliferation by OX-LDL is
      unknown. We hypothesized that OX-LDL may mediate SMC proliferation by activation
      of phospholipase D (PLD) through the generation of the second-messenger,
      phosphatidic acid (PA). To test this hypothesis, activation of PLD by OX-LDL was
      investigated in [3H]myristic acid- or [32P]orthophosphate-labeled rabbit femoral
      artery smooth muscle cells (RFASMC) in the presence of 0.5% ethanol or 0.05%
      butanol. Phospholipase D activation, as measured by labeled phosphatidylethanol
      (PEt) or phosphatidylbutanol (PBt) formation, was enhanced (3- to 5-fold) by OX
      LDL. This activation of PLD was specific for OX-LDL, as native LDL or acetylated
      LDL had no effect. Further, OX-LDL-mediated [32P]PEt formation was dose- and time
      dependent. To determine the mechanism(s) of OX-LDL-induced PLD activation, the
      role of protein kinase C (PKC) and Ca2+ was investigated. Pretreatment of
      [32P]orthophosphate-labeled RFASMC with known inhibitors of PKC such as
      staurosporine, calphostin-C, or H-7, had no effect on OX-LDL-induced PLD
      activation. Also, down-regulation of PKC by 12-O-tetradecanoylphorbol 13-acetate
      (TPA) (100 nM, 18 h) did not alter the OX-LDL-mediated [32P]PEt formation.
      However, pretreatment of RFASMC with genistein, a putative inhibitor of tyrosine
      kinases, attenuated the OX-LDL-mediated [32P]PEt formation. In addition, exposure
      of RFASMC to sodium orthovanadate, an inhibitor of phosphatases, enhanced the OX
      LDL-mediated PLD activation. The effects of genistein and vanadate on PLD
      activation were specific for OX-LDL as these agents did not alter the TPA-induced
      [32P]PEt formation. Treatment of quiescent RFASMC with OX-LDL increased
      [3H]thymidine incorporation into DNA. This enhanced incorporation of
      [3H]thymidine into DNA was also mimicked by exogenously added phosphatidic acid
      (PA) or lysophosphatidic acid (LPA). These findings suggest that OX-LDL is a
      potent activator of the PLD pathway in SMC. The activation of PLD by OX-LDL
      generates second-messengers like PA and/or LPA which modulate mitogenesis. Thus,
      these results indicate that OX-LDL, in atherosclerotic lesions, may enhance SMC
      proliferation through the modulation of signal transduction pathways including
      activation of PLD.

PMID- 8558089
TI  - Exchange of oxidized cholesteryl linoleate between LDL and HDL mediated by
      cholesteryl ester transfer protein.
AB  - This study examines the cholesteryl ester transfer protein (CETP)-mediated
      exchange of cholesteryl linoleate hydroperoxide (Ch18:2-OOH) and cholesteryl
      linoleate hydroxide (Ch18:2-OH) between low density lipoprotein (LDL) and high
      density lipoprotein (HDL). When [3H]Ch18:2-OOH- and [3H]18:2-OH-labeled LDL were
      incubated at 37 degrees C for 0-24 h with unoxidized HDL and purified CETP,
      Ch18:2-OOH and Ch18:2-OH accumulated in the HDL. Similarly, when incubations were
      carried out with [3H]Ch18:2-OOH- and [3H]Ch18:2-OH-labeled HDL, unoxidized LDL,
      and CETP, Ch18:2-OOH and Ch18:2-OH accumulated in the LDL. Comparable results
      were obtained for the CETP-mediated transfer of [3H]Ch18:2-OH alone from LDL to
      HDL. Transfer to HDL of oxidized cholesteryl linoleate from [3H]Ch18:2-OOH- and
      [3H]Ch18:2-OH-labeled LDL was comparable to that of unoxidized cholesteryl
      linoleate (Ch18:2). However, the rate of transfer of [3H]Ch18:2-OOH and
      [3H]Ch18:2-OH from LDL to HDL increased linearly as the molar ratio of acceptor
      (HDL) to donor (oxidized LDL) particles in the incubation increased from 0.5:1 to
      10:1. This increased rate of exchange was accompanied by an increased proportion
      of the oxidized Ch18:2 being present as the hydroxide rather than hydroperoxide.
      Further increases in the molar ratio of HDL to oxidized LDL particles neither
      affected the transfer rate nor the extent of reduction of Ch18:2-OOH to Ch18:2
      OH. We therefore conclude that i) CETP mediates bidirectional transfers of Ch18:2
      OOH and Ch18:2-OH between HDL and LDL; ii) CETP does not distinguish between
      Ch18:2-OOH, Ch18:2-OH, and Ch18:2 as it mediates their exchange between HDL and
      LDL; and iii) association with HDL hastens the reduction of Ch18:2-OOH to Ch18:2
      OH.

PMID- 8558090
TI  - Immunoelectron microscopy of low density lipoproteins yields a ribbon and bow
      model for the conformation of apolipoprotein B on the lipoprotein surface.
AB  - In the present study, the relative positions of 11 anti-apolipoprotein B
      monoclonal antibodies have been mapped onto the surface of human low density
      lipoproteins by electron microscopy. As the epitopes recognized by these
      antibodies have been previously located on the primary sequence of apoB, these
      data provide a map of the configuration of the protein on the surface of the LDL.
      The first 89% of apoB-100 may be modeled as a thick ribbon that wraps once around
      the LDL, completing the encirclement by about amino acid residue 4050. The
      thickness of the ribbon is sufficient to penetrate the monolayer, so that it
      makes contact with the core. There is a kink in the ribbon beginning almost
      halfway along its length at approximately apoB-48. The C-terminal 11% of apoB
      constitutes the "bow," an elongated structure of about 480 residues, beginning at
      4050 and stretching back into one hemisphere and then crossing the ribbon into
      the other hemisphere between residues 3000 to 3500, thus bringing sequences in
      the C-terminal portion of apoB-100 near to the suggested binding site for the LDL
      receptor. The C-terminal sequences may act as a negative regulator of LDL
      receptor binding, in agreement with Parhofer et al, 1992. J. Clin. Invest. 89:
      1931-1937, who reported the enhanced clearance from plasma of apoB-89-containing
      lipoproteins. It is proposed that in VLDL the bow could function to inhibit
      binding to the receptor; during lipolysis to form LDL, it is suggested that these
      C-terminal inhibitory sequences forming the bow would move sufficiently to allow
      interaction with the LDL-receptor.

PMID- 8558091
TI  - Features of cholesterol structure that regulate the clearance of chylomicron-like
      lipid emulsions.
AB  - Cholesterol is an absolute requirement for the clearance from plasma of the
      remnants of triglyceride-rich lipoproteins. Our laboratory previously established
      that cholesterol was essential for the hepatic uptake of remnant particles after
      intravenous injection of chylomicron-like lipid emulsions (1). The aim of the
      present study was to determine the structural features of the cholesterol
      molecule that regulate the metabolism of chylomicrons. Chylomicron-like lipid
      emulsions, which reflect the size and composition and mimic the physiology of
      lymph chylomicrons, were prepared with tracer amounts of labeled triolein
      ([14C]TO) and cholesteryl oleate ([3H]CO) to follow the hydrolysis of
      triglyceride and the uptake of chylomicron remnant particles by the liver.
      Sterols selected as cholesterol congeners with functional group variations were
      incorporated into the emulsions in place of cholesterol and injected
      intravenously in rats. Control emulsions contained either no cholesterol or
      approximately 1% (by weight) cholesterol. The effects of the different sterol
      structures on lipolysis and hepatic remnant uptake were compared with controls to
      determine the significance of various functional groups. Clearance of emulsion CO
      was impaired when cholesterol was absent or replaced by cholesteryl chloride,
      cholesteryl formate, or 3-keto-cholesterol. Clearance of emulsions containing
      epicholesterol, where the OH group at the 3-position is in the alpha
      configuration, was similar to control emulsions containing cholesterol. Congeners
      with an additional hydroxyl group, viz. 7 alpha-hydroxycholesterol, 7 beta
      hydroxycholesterol, or 25-hydroxycholesterol, reduced CO clearance. Androstenol,
      which lacks the side chain at the C17-position, also retarded CO clearance from
      plasma. In contrast, emulsions incorporating congeners with side chain variations
      such as campesterol, beta-sitosterol, stigmasterol, or saturated congeners of
      cholesterol such as cholestanol, coprostanol and its epimer, epicoprostanol, all
      were cleared similarly to emulsions containing cholesterol. In conclusion, for
      physiological clearance of a chylomicron-like emulsion, the presence of a
      hydroxyl (-OH) group at the 3-position and an alkyl side chain at the C17
      position of cholesterol are essential, while the structure of the side chain and
      the saturation of the ring structure are not critical. The mechanism of the
      specificity of sterols on the metabolism of protein-free emulsions is unclear,
      but does not relate to changes in microfluidity of the surface lipids, nor to the
      amount or isoform of associated apolipoproteins.

PMID- 8558092
TI  - A rapid, simple high capacity cholesterol crystal growth assay.
AB  - Cholesterol crystal "nucleation time", more recently referred to as cholesterol
      crystal observation time, is defined as the first appearance of cholesterol
      crystals from isotropic crystal-free biles on light microscopy. This test is used
      to assess the potency of nucleating agents. Crystal appearance has conventionally
      been determined by polarizing light microscopy and crystal growth by counting the
      number of crystals. In this study we adapted a spectrophotometric method to a
      microtiter plate reader to generate cholesterol crystal growth curves. Model
      biles were prepared with a cholesterol saturation of 1.2 to 1.3 and total lipid
      concentration of 10.7 g/dl (taurocholate, 125 mM; cholesterol, 16.8-18.4 mM;
      phospholipid, 43 mM). Pronucleating IgM samples were used to establish and
      validate the assay. Cholesterol crystal growth curves were generated by reading
      absorption at 630 nm daily on a Dynatech microplate reader. Results were
      correlated to cholesterol crystal counts as determined by polarizing light
      microscopy. Standard curves generated from absorbencies of known masses of
      cholesterol crystals were used to quantify the mass of cholesterol crystals
      formed over the observation period. The assay was applied to known pronucleating
      biliary immunoglobulins. Results obtained were similar to our previous report
      that biliary IgM is more potent than biliary IgG. We conclude that using
      microplates and a microtiter plate reader provides a rapid high capacity method
      for detecting cholesterol crystal growth to assess potential nucleating agents in
      nucleation assays.

PMID- 8558093
TI  - Serum concentration of 7 alpha-hydroxycholesterol as an indicator of bile acid
      synthesis in humans.
AB  - The serum concentration of 7 alpha-hydroxycholesterol as an indicator of total
      bile acid synthesis was investigated under different experimental conditions in
      humans. 7 alpha-Hydroxycholesterol was measured by gas-liquid chromatography-mass
      spectrometry, using [2H7]7 alpha-hydroxycholesterol and/or 5 alpha-cholestane-3
      beta, 6 beta-diol as internal standards, and bile acid synthesis was estimated by
      the fecal balance method. Intraindividual variation was small when the
      concentration of 7 alpha-hydroxycholesterol was determined twice in the same
      subject 2 days to 11 months apart (7.3 +/- 6.5%, n = 52). In patients with
      advanced cirrhosis of the liver (n = 22) 7 alpha-hydroxycholesterol was 3.4-fold
      lower (22 ng/ml +/- 8) compared to matched controls (75 ng/ml +/- 19).
      Administration of cholestyramine (4 g b.i.d.) for 14 days increased 7 alpha
      hydroxycholesterol concentration in five healthy volunteers from 40 +/- 11 ng/ml
      to 181 +/- 95 ng/ml (P = 0.02) and fecal excretion of acidic sterols from 254 +/-
      60 mg/d to 1336 +/- 344 mg/d (P < 0.01). Although a significant correlation was
      found between 7 alpha-hydroxycholesterol in serum and bile acid synthesis in
      patients with hypercholesterolemia (r = 0.847, P < 0.001, n = 17), it was
      impossible to accurately determine bile acid synthesis from the serum levels of 7
      alpha-hydroxycholesterol. Thus, determination of 7 alpha-hydroxycholesterol
      concentrations in serum can be used to assess changes in bile acid synthesis
      rates over short and long term periods under various experimental conditions, but
      not to calculate bile acid synthesis correctly.

PMID- 8558094
TI  - HLA-B5 in the diagnosis of Behcet's disease.
AB  - Behcet's disease, a multisystem disease is, by its nature, difficult to diagnose.
      The first manifestation of the disease may precede the appearance of other
      symptoms and signs essential for diagnosis by many years. In patients of
      Mediterranean origin, the early manifestations of the disease, may be confused
      with those of familial Mediterranean fever (FMF). Determination of HLA-B5 may,
      however, contribute to the diagnosis in children with partial manifestations of
      Beh,cet syndrome.

PMID- 8558095
TI  - High incidence of occult thyroid disease among general medical ward patients.
AB  - The objective of this study was to prospectively determine the efficacy of the
      results of routine testing of thyroid functions in patients admitted to a general
      medical ward. Blood for thyroid function tests was drawn on admission as part of
      the laboratory screening panel from 270 consecutive patients. Fifty-one were
      excluded due to recognition of thyroid-related problems by the clinical staff.
      138 patients (63%) had normal free thyroxin (FT4) levels, one patient had
      hyperthyroidism, 15 patients (6.8%) had laboratory primary hypothyroidism and 65
      patients (29.6%) had equivocal results (FT4 < 0.9 ng/dL and TSH < 5.0 mmu/L). In
      eight out of 31 patients in the latter group, the thyroid releasing hormone (TRH)
      test revealed primary or secondary hypothyroidism. A total of 55 patients (25.1%)
      expired within one year. The mortality rate was significantly higher among the
      low FT4 patients (p < 0.01), and was independent of age and sex. We conclude that
      inclusion of FT4 in a laboratory screening panel will reveal a large patient
      population with abnormal results. However, establishing the diagnosis requires
      additional tests. Therefore, screening for occult hypothyroidism among a select
      population, not the acutely sick, populations may be more efficient.

PMID- 8558096
TI  - Elevation of ALT to AST ratio in patients with enteroviral myocarditis.
AB  - Enteroviral myocarditis is often a relatively benign condition in adults.
      Physicians, therefore, may not always record detailed clinical and laboratory
      data in such patients. As such, they may not recognize viral involvement in
      organs beyond the heart. The purpose of this study was to examine the hepatic
      involvement of enteroviral peri-myocarditis and to compare the other diseases
      with congestive heart failure. We analyzed 18 patients (ages 15-64) who were
      diagnosed as having enteroviral myocarditis (n = 16) or pericarditis (n = 2).
      Serology was positive for coxsackie viruses in 11 patients and echoviruses in six
      patients. A diagnosis of hepatic involvement was made by the following laboratory
      data: rising levels of alanine amino transferase (ALT), aspartate amino
      transferase (AST) and exceeded serum ALT compared with AST levels. A ratio of
      ALT/AST more than 1.0 was greatly frequent in patients with peri-myocarditis
      (72%; 13/18) compared with acute myocardial infarction (0%; 0/10) and idiopathic
      dilated cardiomyopathy (3%; 3/10). In summary, hepatic involvement in the setting
      of acute enteroviral peri-myocarditis may be considerably more common in adults
      than previously suspected. The recognition of hepatic involvement in association
      with enteroviral peri-myocarditis may allow improvement of diagnostic sensitivity
      and alter approaches to treatments of acute viral myocarditis.

PMID- 8558097
TI  - Possible evidence that the herbal medicine shakuyaku-kanzo-to decreases
      prostaglandin levels through suppressing arachidonate turnover in endometrium.
AB  - The herbal medicine shakuyaku-kanzo-to has been used for the treatment of
      dysmenorrhea. We attempted to establish the effects of shakuyaku-kanzo-to on
      prostaglandin (PG) levels and the turnover of arachidonic acid in endometrial
      cells. Human endometrial cells isolated from proliferative-phase endometria were
      examined. Arachidonic acid reacylation activity was determined by [3H]arachidonic
      acid incorporation into endometrial cell phospholipid. Its deacylation rate was
      determined by both 3H-liberation from [3H]-arachidonic acid-labelled
      phospholipids and production of lyso-phospholipid. [3H]-PG levels were also
      analyzed. Shakuyaku-kanzo-to enhanced the rate and maximal level of arachidonic
      acid incorporation by 1.5-fold into phosphatidyl-ethanolamine and
      phosphatidylcholine. Degradation of the phospholipids to liberate arachidonic
      acid and lyso-derivatives was not affected by the shakuyaku-kanzo-to. Shakuyaku
      kanzo-to decreased PG levels by approximately 50% of control. Because shakuyaku
      kanzo-to stimulates arachidonic acid esterification to phospholipids, it seems
      likely that shakuyaku-kanzo-to depletes cellular free arachidonic acid with a
      consequent suppression of prostaglandin synthesis. Shakuyaku-kanzo-to may exert
      its action against dysmenorrhea through preventing prostaglandin production.

PMID- 8558098
TI  - Analysis of responses to vancomycin in carotid blood flow in the male rat.
AB  - Vancomycin is known to cause vasodilation, and hypotension secondary to histamine
      release. We studied the actions of two forms of vancomycin, a clinically
      available preparation, clinical vancomycin, and a research grade preparation,
      laboratory vancomycin, in the presence of an H1 receptor blockade and during H2
      receptor blockade with Doppler flow probe analysis of carotid artery flow rate.
      Clinical vancomycin, laboratory vancomycin, and histamine, increased the mean
      carotid artery blood flow from baseline in a dose-dependent manner.
      Diphenhydramine, H1 receptor antagonist, attenuated the increase in mean carotid
      artery blood flow for the highest dose of clinical vancomycin and for each dose
      of histamine. Famotidine, H2 receptor antagonist, significantly attenuated the
      increase in mean carotid artery blood flow for the highest dose of clinical
      vancomycin, the two higher doses of laboratory vancomycin, and with each dose of
      histamine. Both diphenhydramine and famotidine attenuated the increase of mean
      carotid artery blood flow with clinical vancomycin, laboratory vancomycin, and
      histamine. These data suggest that the change in carotid flow produced by
      vancomycin, is dependent, in part, on either H1 or H2 receptor activation.

PMID- 8558099
TI  - Fetal blood sampling in the assessment of acute nonimmune hydrops fetalis.
AB  - Nonimmune hydrops fetalis can be associated with many fetal conditions. A fetal
      blood sample obtained from ultrasound-guided cordocentesis can offer vital
      information about the underlying cause of the nonimmune hydrops fetalis, and
      perinatal management can be planned accordingly. We attempted to evaluate a case
      of nonimmune hydrops fetalis conveying poor perinatal outcome through serial
      fetal blood sampling. Although we could establish no apparent reason for this
      acute case, fetal blood sampling in addition to ultrasonographic screening can
      play a key role in the management of the 'perplexing' nonimmune hydrops fetalis.

PMID- 8558100
TI  - Tissue factor pathway inhibitor activity in factor VII deficiency.

PMID- 8558101
TI  - Further clinical studies of curdlan sulfate (CRDS)--an anti-HIV agent.
AB  - Curdlan sulfate (CRDS) is a semi-synthetic sulfated polysaccharide which inhibits
      the attachment of HIV to T-cells, and also has intracellular anti-HIV activity.
      In Phase I clinical trials, CRDS was found in 4 hr i.v. infusions, to be well
      tolerated up to 200 mg/70 kg and unexpectedly to produce marked, dose-related
      increases in CD4 lymphocytes in HIV-infected patients. Prolongation of bleeding
      time is expected to be the dose limiting toxicity, but no episodes of bleeding
      were seen. In one of the studies in this report, CRDS was administered i.v. daily
      for 7 days to HIV patients at doses of 40, 100, 140 and 180 mg/70 kg/day. At the
      higher doses, marked increases in CD4 and CD8 lymphocytes were observed. These
      increases mainly returned to baseline after 24 hr. To further delineate the
      pharmacokinetics of these changes in CD4 and CD8 lymphocytes, another Phase I
      study was done in which CRDS was infused i.v. over a 30 min period in HIV
      patients at single doses of 25, 50, 75, 100, 125, 150, 175 and 200 mg/70 kg/day.
      The drug was well tolerated in all cases and marked increases in CD4 lymphocytes
      were again seen at the higher doses, in some cases amounting to increases of 500
      cells/mm3 after a single dose. The half-life of CRDS in man was found to be about
      two hours, as measured by activated partial thromboplastin time (APTT) and by
      plasma assays.

PMID- 8558102
TI  - Everything, and more, I know about x-rays.

PMID- 8558103
TI  - Roentgen. Early radiology, and subsequent development of diagnostic radiology. A
      history.

PMID- 8558104
TI  - History of radiation oncology.

PMID- 8558105
TI  - Nuclear medicine. Reflections in time.

PMID- 8558106
TI  - Emerging from the shadows.

PMID- 8558107
TI  - Research in radiology.

PMID- 8558108
TI  - The J. Maxey Dell physicians. Pioneer Florida radiologists.

PMID- 8558109
TI  - Paul Colson Perry, M.D.. Early Florida radiographer.

PMID- 8558110
TI  - Academic radiology in Florida.

PMID- 8558111
TI  - Impact of health care reform on practice of radiology.

PMID- 8558112
TI  - For the record.
AB  - The management of medical records in the current climate of fragmented and
      managed care has created very real and present difficulties for physicians.
      Florida law protects the patient's right to the medical record and insures
      confidentiality and access. Similar protections for physicians, to allocate the
      costs of 20th century record keeping fairly among the parties, and to insure the
      physician access to information necessary to treat the patient or to defend
      himself, are essential but so far not forthcoming.

PMID- 8558113
TI  - Medicaid spending.

PMID- 8558114
TI  - Micromanaging medicine.

PMID- 8558115
TI  - Pathology and immunogenicity in the cotton rat (Sigmodon hispidus) model after
      infection with a bovine adenovirus type 3 recombinant virus expressing the
      firefly luciferase gene.
AB  - The histopathology of adenovirus pneumonia in cotton rats (Sigmodon hispidus) due
      to bovine adenovirus type 3-luciferase recombinant virus (BAd3-Luc), which has a
      0.7 kb deletion from the early region 3 (E3) replaced with the firefly luciferase
      gene, was compared with that produced by the parental wild-type (wt) bovine
      adenovirus type 3 (BAd3). After intranasal inoculation of cotton rats with 3 x
      10(7) p.f.u. of BAd3-Luc, the infectious virus titres in the lungs at various
      times post-infection were similar to those of animals infected with the parental
      virus. Quantitative analysis of histopathological changes and immunohistochemical
      staining showed that the character and severity of the lesions were
      indistinguishable in the two infections. Luciferase activity was detected in the
      lungs of BAd3-Luc-inoculated animals until 4 days post-infection (p.i.).
      Antibodies to both BAd3 and luciferase were detected in sera collected from BAd3
      Luc-infected animals until at least 6 weeks p.i. These results show that Bad3-Luc
      produces pulmonary lesions in cotton rats similar to those of wt BAd3 and suggest
      that BAd3-based vectors may be suitable for the development of live recombinant
      virus vaccines.

PMID- 8558116
TI  - Unilateral nasal infection of cotton rats with respiratory syncytial virus allows
      assessment of local and systemic immunity.
AB  - An in vivo model for the study of local and systemic effectors of immunity to
      respiratory syncytial virus (RSV) is described. Cotton rats (Sigmodon
      fulviventer) inoculated in one nostril with a small volume (2 microliters) of
      virus suspension contracted a unilateral nasal infection which did not extend to
      the contralateral nasal turbinates, nor to the lungs. Immunity to subsequent RSV
      challenge could be induced by small priming doses ( < 10 p.f.u. per animal), but
      was dependent upon viral replication, as virus inactivated by UV light was not
      immunogenic. Immunity occurred in the absence of detectable neutralizing serum
      antibody. The onset of resistance to viral challenge occurred simultaneously in
      ipsilateral nasal, contralateral nasal and pulmonary tissues. However, low levels
      of transient viral replication occurred in contralateral nasal turbinates and in
      lungs following virus challenge, thus indicating that local components of
      immunity acting at the ipsilateral site of infection were more effective than
      systemic components acting at the other sites. Further evidence is provided to
      suggest that three types of immunological effectors - local, persistent, systemic
      and transient systemic - participate in the immune response to RSV infection.

PMID- 8558117
TI  - Definition and functional analysis of the signal/anchor domain of the human
      respiratory syncytial virus glycoprotein G.
AB  - The attachment protein G of human respiratory syncytial (RS) virus is a type II
      transmembrane glycoprotein. A secreted from of the G protein is also produced. To
      examine the two distinct hydrophobic regions in the N-terminal 63 amino acids of
      G protein for their role(s) in membrane insertion and anchoring, transport to the
      cell surface, and secretion, G proteins that contained point mutations or
      deletions were synthesized by cell-free transcription-translation and in cells by
      expression from recombinant vaccinia virus vectors. A mutant protein lacking the
      entire major hydrophobic region (amino acids 38-63) was not glycosylated, not
      expressed on the cell surface, and not secreted, because it was not inserted into
      membranes. In contrast, deletion of the minor hydrophobic region (amino acids 23
      31) had no detectable effect on membrane insertion or anchoring. These data
      provided direct evidence that amino acids 38-63 were necessary for membrane
      insertion and contained the signal/anchor domain of RS virus G protein. Mutant
      proteins that lacked either the N-terminal or the C-terminal half of this 26
      residue hydrophobic region were inserted into membranes and processed to
      maturity, showing that either half of this region was sufficient for membrane
      insertion. However, these two mutant proteins were secreted more abundantly than
      wild-type G protein. We propose that their truncated hydrophobic domains
      interacted with membranes in a way that mimicked the N-terminal signal sequence
      of naturally secreted proteins, allowing proteolytic cleavage of the mutant
      proteins.

PMID- 8558118
TI  - Functional promoters in the genome of human papillomavirus type 6b.
AB  - Viral mRNAs from lesions containing human papillomavirus type 6 (HPV-6) have
      previously been mapped on the viral DNA but relatively little is known about the
      control of mRNA production, or whether the mapped RNA termini correspond to
      promoters. By analysis of run-off transcripts synthesized in vitro, primer
      extension and measurements of promoter activity in fragments of the viral DNA
      introduced into cells, we have identified three promoters in the early region of
      the HPV-6b genome. These are: (i) at the end of the long control region upstream
      of the E6 open reading frame; (ii) upstream of E7 and (iii) upstream of E1. The
      promoter upstream of E1 was the most active. These results contrast with results
      of similar assays with HPV-18, in which the strongest promoter was that
      controlling expression of the transforming genes E6 and E7. In addition, a novel
      promoter was detected close to E5a, upstream of the late genes.

PMID- 8558119
TI  - Phenotypic mixing with recombinant haemagglutinin of high cleavability mediates
      multi-cycle replication of human influenza virus in cell culture.
AB  - When CV-1 cells expressing haemagglutinin (HA) of fowl plague virus
      A/FPV/34/Rostock(H7) (FPV) from an SV40-based recombinant vector were
      superinfected with the human influenza virus A/FM/1/47(H1N1)(FM1), phenotypically
      mixed progeny virus was observed. It contained cleaved FPV HA and uncleaved FM1
      HA, was infectious without trypsin treatment and its infectivity was
      neutralizable by anti-FPV serum. When superinfection of H7 HA-expressing CV-1
      cells was performed at a low multiplicity of infection, multi-cycle replication
      occurred. Control cells preinfected with an SV40-based recombinant not expressing
      FPV HA did not allow multi-cycle replication. Multi-cycle replication of FM1
      virus was also observed when cells were preinfected with a vector expressing a
      highly cleavable mutant of influenza virus A/Port Chalmers/1/73(H3) HA carrying
      an insert of four arginine residues at the cleavage site. This was not the case
      when cells expressing uncleaved wild-type H3 HA were used. The results show that
      by phenotypic mixing with recombinant HA of high cleavability, a human influenza
      virus can be obtained in infectious form from cells lacking a suitable protease
      to activate this virus.

PMID- 8558120
TI  - Detection of the ORF3 polypeptide of feline calicivirus in infected cells and
      evidence for its expression from a single, functionally bicistronic, subgenomic
      mRNA.
AB  - Feline calicivirus (FCV) is a small positive-stranded RNA virus within the family
      Caliciviridae. Its genome is 7690 nucleotides in length and encodes three open
      reading frames (ORFs). The smallest, ORF3, is located at the extreme 3' end of
      the genome and can potentially encode a polypeptide of approximately 12 kDa. In
      this paper, we report the identification of an ORF3-encoded polypeptide in FCV
      infected cells using an antiserum raised against a bacterially-expressed
      bacteriophage T7 gene 10-ORF3 fusion protein. Although a small mRNA of 0-5 kb,
      which could potentially encode ORF3, has been described, reports on the number
      and size of FCV subgenomic RNAs have varied considerably. To clarify the
      situation, RNAs from FCV-infected cells were labelled in vivo using
      [32P]orthophosphate, an approach which provided definitive data. Only two RNA
      species were detected, the genomic RNA and a subgenomic mRNA of 2.4 kb. The 5'
      end of the subgenomic mRNA was mapped to position 5227 on the genomic RNA using
      RNA sequencing and primer extension methods. RNA isolated from FCV-infected cells
      in which no subgenomic RNA smaller than 2.4 kb was detectable directed the
      synthesis in rabbit reticulocyte lysate of the ORF3-encoded polypeptide.
      Furthermore, a synthetic RNA copy of the 2-4 kb subgenomic mRNA of FCV,
      containing both ORF2 and ORF3 polypeptides in the in vitro translation system.
      These data strongly suggest that ORF3 is expressed from the 2-4 kb subgenomic RNA
      and that this RNA is functionally bicistronic. The possible mechanisms by which
      ORF3 is expressed are discussed.

PMID- 8558121
TI  - Identification of a short domain within the non-structural protein NS2 of
      epizootic haemorrhagic disease virus that is important for single strand RNA
      binding activity.
AB  - The role that a conserved amino acid motif, found in the non-structural protein
      NS2 of orbiviruses, plays in the interaction of this protein with single stranded
      (ss) RNA was investigated by mutation analysis of the NS2 of epizootic
      haemorrhagic disease virus. An NS2 mutant in which this motif (amino acids 75 to
      83) was deleted was expressed in Spodoptera frugiperda cells by a recombinant
      baculovirus and found to be unable to bind to poly(U)-Sepharose. The deletion
      mutant also differed from wild-type NS2 in that it did not appear to be complexed
      with ssRNA in cells infected with the baculovirus recombinant. Furthermore, the
      deletion exerted an adverse effect on the ability of NS2 to form inclusion bodies
      in the cytoplasm of baculovirus-infected insect cells. To further characterize
      the role of this motif in RNA-binding, specific residues within the region were
      substituted by site-directed mutagenesis and the mutants were expressed in
      Escherichia coli as fusion proteins. Analysis of the different mutant proteins
      indicated that in each case ssRNA-binding was impaired relative to that of the
      wild-type NS2 control. The degree of impairment corresponded to the number of
      amino acid substitutions and the largest effects were associated with non
      conserved substitutions. It is suggested that the conserved motif is an important
      structural determinant in the interaction of NS2 with ssRNA.

PMID- 8558122
TI  - Complete nucleotide sequence of the Nilaparvata lugens reovirus: a putative
      member of the genus Fijivirus.
AB  - The nucleotide sequences of all genome segments of the Nilaparvata lugens
      reovirus (NLRV), which is found in the brown planthopper Nilaparvata lugens, have
      been determined and some genes have been assigned to structural and functional
      proteins. The genome of NLRV consists of 28 699 nucleotides and contains at least
      11 large open reading frames (ORFs). The genome of NLRV is the largest among
      viruses of the family Reoviridae reported to date. The deduced amino acid
      sequence of genome segment S1 contained the major motifs of RNA polymerase and
      that of S7 had the purine NTP-binding motif. Based on the molecular masses of the
      deduced proteins and the particle structure of NLRV, segments S1, S3 and S7 were
      assigned to the 160, 140 and 75 kDa proteins, respectively, that are located in
      the inner core. It was deduced that S2 codes for the 135 kDa protein (B spike),
      which is located on the surface of the inner core. Most reported ORFs of rice
      black streaked dwarf virus (RBSDV), which shares many properties with NLRV, had
      similarities with the corresponding ORFs of NLRV. An exception was S7 ORF2, which
      is found in RBSDV but not NLRV and may therefore be involved in multiplication of
      RBSDV in rice plants. These results and our previous observations indicate that
      NLRV should be classified in the genus Fijivirus.

PMID- 8558123
TI  - Effect of mutations on the intracellular localization of Bombyx mori cytoplasmic
      polyhedrosis virus polyhedrin.
AB  - We have already cloned the polyhedrin genes of the wild-type strain H Bombyx mori
      cytoplasmic polyhedrosis virus (BmCPV) and its mutant, strain A. In this work,
      polyhedrin genes of mutant BmCPV strains C1 and C2 were cloned and their
      nucleotide sequences were determined. The polyhedrin amino acid sequences of
      strains C1 and C2 were compared with that of strain H. Strains C1 and C2
      contained two and three sites of mutation in their polyhedrin genes,
      respectively. Four amino acids (249RLLV) were added at the carboxy terminus of
      the polyhedrin of strain A, C1 and C2 and the corresponding polyhedrin genes were
      introduced into a baculovirus expression vector. Intracellular localization of
      expressed polyhedrin as well as the morphology and localization of polyhedra were
      investigated by Western blot and microscopy analysis. Recombinant baculovirus
      containing the polyhedrin gene of strain H produced hexahedral polyhedra in both
      the cytoplasm and the nucleus. However, the hexahedral polyhedra of strain A were
      localized only in the nucleus. Normal polyhedra were not observed in cells
      infected with recombinant baculoviruses expressing strain C1 or C2 polyhedrin
      genes, but amorphous structures were found in infected cells. Results of
      expression of a chimaeric luciferase-containing carboxyl-terminal sequence of
      strain A demonstrated that this sequence was responsible for the nuclear
      localization. We suggest that a mutation at the carboxy terminus of BmCPV
      polyhedrin led to nuclear localization of polyhedrin and that several other
      mutations were responsible for modification of the crystallization pattern of
      polyhedrin.

PMID- 8558124
TI  - Variation of viroid profiles in individual grapevine plants: novel grapevine
      yellow speckle viroid 1 mutants show alterations of hairpin I.
AB  - This is the first report which gives a general survey about viroid variant
      composition in a vineyard and within single plants. A German vineyard with 20
      year-old grapevines (Vitis vinifera) of the cultivars 'Bacchus' and 'Kerner' was
      analysed for viroid infections. Only grapevine yellow speckle viroid 1 (GYSVd1)
      and the grapevine isolate of hop stunt viroid (HSVdg) were detected. Both viroids
      occur in several sequence variations. Eighteen novel GYSVd1 variants and two
      previously published HSVdg main variants with six new minor variants were found.
      They were randomly spread in the vineyard. The distribution of GYSVd1 and HSVdg
      main variants and their accompanying subvariants differed even in neighbouring
      plants. We conclude that these individual viroid variant profiles are the result
      of 20 years of independent evolution, i.e. mutation and selection, in each single
      plant. Four of the nine GYSVd1 main variants were mutated in the inverted repeats
      bordering the central conserved region. These base substitutions decreased the
      thermodynamic stability of a metastable structure called hairpin I.

PMID- 8558125
TI  - Polyomavirus middle-T antigen lacking a membrane anchor sequence accumulates in
      the nucleus.
AB  - Three proteins expressed early in the replicative cycle of polyomavirus also play
      an essential role during virus-mediated tumorigenesis. One of the proteins,
      middle-T antigen, has been shown to bind cellular proteins involved in cell
      signalling such as c-Src, phosphatase 2A, phosphatidylinositol 3-kinase and SHC.
      Association of middle-T antigen with cellular membranes has been shown to be
      essential for middle-T-mediated cell transformation. A mutant virus encoding a
      truncated form of middle-T lacking a carboxy-terminal hydrophobic sequence
      mediating membrane association is not oncogenic. This mutant middle-T still binds
      phosphatase 2A through amino-terminal sequences common to small-and middle-T and
      is localized in the nucleus, although the protein does not contain a classical
      nuclear targeting sequence. Mutations introduced into the amino-terminal domain
      affecting the ability of truncated middle-T to bind phosphatase 2A prevented
      accumulation of the protein in the nucleus and led to localization in the
      cytoplasm. This suggests that nuclear localization of truncated middle-T may be a
      consequence of binding to phosphatase 2A.

PMID- 8558126
TI  - Characterization of phocid herpesvirus-1 and -2 as putative alpha- and
      gammaherpesviruses of North American and European pinnipeds.
AB  - To study the relationships between herpesvirus recently isolated from different
      pinniped species, antigenic and genetic analyses were performed. First,
      herpesviruses isolated from North American harbour seals (Phoca vitulina), a
      Californian sea lion (Zalophus californianus) and a European grey seal
      (Halichoerus grypus) were examined in an enzyme immunoassay (EIA) with a panel of
      monoclonal antibodies which had previously been shown to allow typing of
      herpesviruses from European harbour seals into two distinct virus types: phocid
      herpesvirus type-1 and type-2 (PhHV-1 and PhHV-2). The EIA data showed that all
      but one of the isolates from seals ranging in United States coastal waters were
      PhHV-2-like while the European grey seal herpesvirus was PhHV-1-like. Genetic
      characterization was facilitated by PCR analysis using primers based on conserved
      regions of the glycoprotein B and D (gB and gD) genes of the antigenically
      closely related canid (CHV) and felid (FHV) herpesvirus. Specific amplified
      products were obtained with five isolates antigenically characterized as PhHV-1
      like but not with five PhHV-2-like isolates. Sequence analysis of the PCR
      products confirmed greatest similarity to members of the genus Varicellovirus of
      the Alphaherpesvirinae and in particular to CHV. Sequence analysis of two EcoRI
      fragments of the PhHV-2 genome (European isolate 7848) revealed greatest
      similarity to gammaherpesviruses and in particular equine herpesvirus-2. Although
      an unambiguous subgrouping was not feasible, this is the first evidence that PhHV
      2 may be a putative gammaherpesvirus of pinnipeds.

PMID- 8558127
TI  - Gene organization in the UL region and inverted repeats of the canine herpesvirus
      genome.
AB  - Restriction mapping and the determination of scattered nucleotide sequences have
      permitted a description of the global structure and evolutionary affinities of
      the canine herpesvirus (CHV) genome. The global structure closely resembles that
      of the totally sequenced genomes of varicella-zoster virus and equine herpesvirus
      1 (EHV-1) in having a 37 bp inverted repeat flanking a long unique region (UL) of
      approximately 100,000 bp, and a 10,100-10,700 bp inverted repeat flanking a short
      unique region (U8) of roughly 7,400-8,600 bp. On the basis of the sequences
      obtained, 35 homologues to previously identified herpesvirus gene products were
      found in UL and the major inverted repeat, and the level of the similarities
      indicated that CHV belongs to the genus Varicellovirus. Within the genus, CHV
      appears to be most closely related to EHV-1, pseudorabies virus and feline
      herpesvirus. Surprisingly, genes for both subunits of the viral ribonucleotide
      reductase were found to be missing from their equivalent place in other
      herpesvirus genomes. Either they have been translocated to another position in
      the CHV genome or, we think more likely, they have been lost.

PMID- 8558128
TI  - Assessment of antigenicity and genetic variation of glycoprotein B of murine
      cytomegalovirus.
AB  - An analysis of linear antibody-binding sites of the glycoprotein B (gB) molecule
      of murine cytomegalovirus (MCMV) and of genetic variation within these regions
      was performed. To achieve this, a series of overlapping fragments spanning the
      entire coding sequence of the gB gene of the K181 strain of MCMV was expressed in
      E. coli as fusion proteins with glutathione S-transferase (GST) using the pGEX
      expression system. Four antibody-binding regions were mapped to locations
      spanning amino acid residues 17-79 (BS), 155-278 (BE2), 809-926 (SS) and 347-508
      (BB and EE), based on reactivity in Western blot analysis of GST-gB fusion
      proteins with murine polyclonal antiserum raised against MCMV. Only the antibody
      binding region BE2 (155-278) elicited an antiserum that exhibited complement
      dependent neutralizing activity, and immunization of mice with the fusion protein
      BE2 led to moderate but significant reductions in the level of MCMV replication
      in the spleen. Polyclonal antisera raised against the GST-gB fusion proteins
      detected purified virion proteins of 105 kDa (anti-BS and anti-BE2) and 52 kDa
      (anti-SS) and are therefore likely to recognize the N-terminal and C-terminal
      portions of the gB molecule, respectively. The antibody-binding region within
      amino acid residues 17-79 was found to be MCMV strain-specific, whereas antibody
      binding regions within residues 155-278 and 809-926 were found to be conserved
      among MCMV field isolates. Comparative sequence analysis of the corresponding
      regions of MCMV gB revealed a level and extent of sequence of sequence
      heterogeneity consistent with these findings.

PMID- 8558129
TI  - Role of apical and basolateral membranes in replication of human cytomegalovirus
      in polarized retinal pigment epithelial cells.
AB  - Human retinal pigment epithelial (RPE) cells, which are permissive for human
      cytomegalovirus (HCMV) replication, were used to evaluate virus infection from
      apical and basolateral membranes of polarized cells. Tests of HCMV infectivity
      showed that the apical membrane was 20-30-fold more susceptible to infection than
      the basolateral membrane; in contrast, both membranes were equally susceptible to
      infection by herpes simplex virus type 1 (HSV-1). Neutralizing monoclonal
      antibodies (MAbs) to HCMV glycoprotein B (gB) blocked penetration of virions into
      polarized RPE cells. This indicated that gB has a function in fusion of the
      virion envelope with the apical membrane of these cells, as it has with the cell
      membrane of unpolarized human fibroblasts. In contrast to HSV-1-infected RPE
      cells, the paracellular permeability of polarized RPE cells changed slowly
      following infection with HCMV. Confocal microscopy examination of HCMV-infected
      RPE cells revealed that the pattern of ZO-1 staining was altered at late times.
      Addition of gB-specific neutralizing MAbs to the apical and basolateral membranes
      of HCMV-infected RPE cells failed to inhibit plaque development; this indicated
      that progeny virions infect adjacent cells before disassembly of tight junctions
      and are sequestered from neutralization during spread across lateral cell
      membranes. The finding that progeny HCMV virions cross lateral cell membranes,
      which differ substantially in protein composition from apical membranes, suggests
      that polarized RPE cells contain multiple receptors for HCMV.

PMID- 8558130
TI  - N-terminal sequence analysis of equine herpesvirus 1 glycoproteins D and B and
      evidence for internal cleavage of the gene 71 product.
AB  - Signal cleavage sites of equine herpesvirus 1 (EHV-1) glycoproteins D and B (gD
      and gB) and an endoproteolytic cleavage site of EHV-1 gB were determined by N
      terminal amino acid sequencing and compared with known cleavage sites of
      homologues in other herpesvirus. Signal cleavage of EHV-1 gD occurred between
      Arg35 and Ala36 in a region of basic amino acids resembling the endoproteolytic
      cleavage sites of viral glycoproteins, nine amino acids downstream of the
      predicted site, while EHV-1 gB was cleaved as predicted between Ala85 and Val86.
      Endoproteolytic cleavage of EHV-1 gB occurred between Arg548 and Ala549, 28 amino
      acids downstream of the cleavage site predicted from conserved sequences of other
      herpesvirus gB homologous. One interpretation of these data is that EHV-1 gB is
      cleaved internally at both sites, a possibility which was supported by the
      apparent molecular masses of the unglycosylated gB subunits produced in the
      presence of tunicamycin. This double cleavage would release a stretch of amino
      acids which is not present in sequenced gB molecules of other herpesviruses.
      Experiments with glycosylation inhibitors indicated that cleavage of EHV-1 gB can
      occur in the absence of glycosylation. N-terminal sequencing also determined that
      a 42 kDa EHV-1 glycoprotein was a product of internal cleavage of the protein
      encoded by gene 71. Staggered endoproteolytic cleavage after adjacent arginine
      residues 506 and 507 separates the 42 kDa C-terminal subunit containing all the
      cysteine residues from the serine and threonine rich N-terminal region.

PMID- 8558131
TI  - Essential role of NF-kappa B in transactivation of the human immunodeficiency
      virus long terminal repeat by the human cytomegalovirus 1E1 protein.
AB  - The 72 kDa 1E1 protein of human cytomegalovirus (HCMV) is one of a few viral
      regulatory proteins expressed immediately after infection of a host cell.
      Although it is now well-established that 1E1 is a potent transcriptional
      activator of the human immunodeficiency virus (HIV) long terminal repeat (LTR),
      the identity of the nucleotide sequence responsive to 1E1 remains elusive and the
      molecular mechanism of this interaction is not well-understood. We have
      constructed various LTR mutants and tested them for their ability to be activated
      by 1E1 using transient transfection assays. Mutations in the NF-kappa B sites, of
      either a few changes in the nucleotide sequence or a deletion of the entire
      region, abrogated 1E1-driven transactivation. Deletion of the Tat-responsive
      element (TAR) had no significant effect on reporter expression. Mutations in the
      Sp1 sites or the TATA box significantly lowered LTR activity, but this is
      probably due to an effect on the general transcription system, as these elements
      are also required for the transactivation of the LTR by many stimulators
      including Tat, tumour necrosis factor alpha (TNF-alpha). E1A/E1B and phorbol
      myristate acetate (PMA). In addition, gel retardation analysis demonstrated that
      NF- kappa B activity was significantly increased in human T lymphoid H9 and
      monocytic U937 cell lines constitutively expressing 1E1. Taken together, these
      data suggest that NF- kappa B plays a central role in the 1E1 transactivation of
      the HIV LTR.

PMID- 8558132
TI  - Comparative study of the cell tropism of feline immunodeficiency virus isolates
      of subtypes A, B and D classified on the basis of the env gene V3-V5 sequence.
AB  - Feline immunodeficiency virus (FIV) isolates have been classified into subtypes
      A, B, C and D based on the env gene V3-V5 sequence. The cell tropism of seven new
      Japanese isolates and a Petaluma (prototype) isolate of FIV, which classified
      into subtypes A, B and D, for feline lymphoblastoid and feline fibroblastoid cell
      lines was compared. FeT-1 (CD4+/-, CD8-, AND CD9+2) and Kumi-1 (CD4+2, CD8- and
      CD9+2) cells were used as the interleukin-2 (IL-2)-dependent feline T-lymphocyte
      cell lines and FeT-J (CD4+, CD8+/- and CD9+2) and 3201 (CD4+2, CD8+ and CD9-)
      cells were used as the IL-2- independent feline T-lymphocyte cell lines. The
      feline fibroblastoid cell lines used were Crandell feline kidney (CrFK) and fewf
      4 (both CD4-, CD8- and CD9+2) cells. All FIV isolates replicated in all
      lymphoblastoid cell lines used. All isolates showed the greatest
      cytopathogenicity for Kumi-1 cells. All isolates replicated even in the CD9
      negative 3201 cells. More isolates caused persistent infection in IL-2
      independent cell lines than in IL-2-dependent cell lines. The number of subtype B
      isolates that established persistent infection was limited, only one of four
      strains. Only the subtype A isolates replicated in CrFK cells, whereas none of
      the isolates replicated in fewf-4 cells, which have similar cell surface markers
      to CrFK cells. The subtype A viruses (CrFK/Petaluma, CrFK/Sendai-1) growing in
      CrFK cells showed greater cytopathogenicity for lymphoblastoid cell lines than
      did those (FL-4/Petaluma, Kumi-1/Sendai-1) growing in a lymphoblastoid cell line.

PMID- 8558133
TI  - A kinetic study of iron release from Azotobacter vinelandii bacterial ferritin.
AB  - The kinetics of iron release from Azotobacter vinelandii bacterial ferritin
      (AVBF) was measured by reduction of core iron with S2O4(2-) followed by chelation
      of Fe2+ with alpha, alpha-bipyridine (bipy). The rate was first order in AVBF and
      one half order in S2O4(2-), suggesting that SO2- is the active reductant formed
      by S2O4(2-) = 2SO2-. With zero-order conditions for dithionite and bipy, two
      consecutive first-order iron release reactions differing by a factor of about 14
      were observed with rate constants of 0.0263 and 0.00184 sec-1, respectively, at
      25 degrees C and pH 7.0. The faster reaction corresponded to the loss of 1433
      iron atoms (91%) and the slower second reaction corresponded to loss of 145 (9%)
      of the original 1575 iron atoms present. The first reaction increased about
      twofold with pH variation between 6.5 and 8.0, whereas the second reaction was
      unchanged in the pH range 5.5-8. Both dramatically increased at pH 5.0. Methyl
      viologen increased the rate of both reactions about tenfold. The biphasic
      behavior for iron loss is interpreted as two different populations of iron atoms
      present in the core of AVBF, the first representing the bulk iron, and the second
      a group of unique iron atoms released last which may represent iron attached to
      the interior of the protein shell or iron associated with the heme groups.
      Kinetic stopped-flow measurements show that the heme is first reduced, followed
      by reduction of the core iron by reduced heme, suggesting an electron transfer
      role for heme in AVBF function.

PMID- 8558134
TI  - Investigation on the mechanism of peptide chain prolongation on montmorillonite.
AB  - Experiments with reduced-charge montmorillonites with gradually collapsed
      interlayer space prove that peptide formation processes occur mainly at the edges
      of the clay mineral. Activation of peptides and amino acids and the intermediate
      formation of cyclic anhydrides are found to be the two dominant processes
      determining the formation of higher peptides on the mineral surface.

PMID- 8558135
TI  - Sentinel lesions of primary CNS lymphoma.
AB  - Some patients ultimately diagnosed with primary CNS lymphoma (PCNSL) have
      transient symptomatic contrast enhancing lesions. These "sentinel lesions" of
      PCNSL recede spontaneously or with corticosteroid treatment and present an
      important diagnostic dilemma because they show variable, but non-diagnostic
      histopathological features. Four previously healthy, immunocompetent patients
      aged 49 to 58 years had contrast enhancing intraparenchymal brain lesions. Before
      biopsy, three of the four were treated with corticosteroids. Initial biopsies
      showed demyelination with axonal sparing in two, non-specific inflammation in
      one, and normal brain in one. Infiltrating lymphocytes predominantly expressed T
      cell markers with rare B cells. All four patients recovered within two to four
      weeks after the initial biopsy and imaging studies showed resolution of the
      lesions. The CSF was normal in three of the four patients tested; oligoclonal
      bands were absent in both of the two tested. After seven to 11 months, each
      patient developed new symptomatic lesions in a different region of the brain,
      biopsy of which showed a B cell PCNSL. The mechanism of spontaneous involution of
      sentinel lesions is not understood, but may represent host immunity against the
      tumour. Sentinel lesions of PCNSL should be considered in patients with contrast
      enhancing focal parenchymal lesions that show non-specific or demyelinative
      histopathological changes. Close clinical and radiographic follow up is essential
      if PCNSL is to be diagnosed early in such patients.

PMID- 8558136
TI  - The moving ear syndrome: a focal dyskinesia.

PMID- 8558137
TI  - Acute anterior horn cell disease resembling poliomyelitis as a manifestation of
      respiratory syncytial virus infection.

PMID- 8558138
TI  - Hereditary defect of cobalamin metabolism (homocystinuria and methylmalonic
      aciduria) of juvenile onset.

PMID- 8558139
TI  - Detection of dilated subarachnoid space around the optic nerve in patients with
      papilloedema using T2 weighted fast spin echo imaging.

PMID- 8558140
TI  - Alzheimer's disease in a case of cortical basal ganglionic degeneration with
      severe dementia.

PMID- 8558141
TI  - Proceedings of the Association of British Neurologists and the British
      Neuropsychological Society, the Commonwealth Institute. London, 28-29 September
      1995. Abstracts.

PMID- 8558142
TI  - Multiple myeloma presenting as the Collet-Sicard syndrome.

PMID- 8558143
TI  - MRI dynamics of brain and spinal cord in progressive multiple sclerosis.
AB  - OBJECTIVE: To assess the usefulness of serial cord MRI in patients with
      progressive multiple sclerosis. METHODS: Monthly MRI of the brain and spinal cord
      with and without gadolinium enhancement was carried out in 19 patients with
      progressive multiple sclerosis (10 primary progressive, nine secondary
      progressive) over the course of one year. RESULTS: During this period there were
      132 active lesions in the brain and only six in the cord. One hundred and twelve
      (85%) active brain lesions occurred in the secondary progressive group; three new
      cord lesions occurred in each group. In the secondary progressive group MRI
      activity was high in patients who had superimposed relapses, whereas in those who
      progressed without relapse and in the primary progressive group it was low. Cross
      sectional areas of the cord decreased at the C5 level in both groups, implying
      progressive atrophy of fibre tracts. There was no relation between either brain
      or cord MRI activity and change in disability over the study period. CONCLUSIONS:
      Although the detection of new lesions by frequent cord imaging using current
      technology has little role in the monitoring of disease activity in progressive
      multiple sclerosis, the serial measurement of cord cross sectional area may be
      important. There is also evidence to suggest that the mechanism underlying
      irreversible disability in patients with progressive multiple sclerosis may be
      different in patients who continue to relapse than in those who do not.

PMID- 8558144
TI  - Management of primary malignant brain tumours.

PMID- 8558146
TI  - A study of oligoclonal band negative multiple sclerosis.
AB  - OBJECTIVES: To determine whether oligoclonal band (OCB) negative multiple
      sclerosis is a reliable diagnosis and, if so, whether it has a distinctive
      prognosis. METHODS: Retrospective and matched prospective comparison of the
      clinical and laboratory features of patients with clinical definite multiple
      sclerosis with and without intrathecal synthesis of oligoclonal IgG. RESULTS:
      Thirty four patients were identified with apparent OCB negative clinically
      definite multiple sclerosis. The results of oligoclonal banding proved to have
      been equivocal in 14 of 34; the clinical diagnosis of multiple sclerosis was
      questionable in 8 of 34. The remaining 12 patients with "true" OCB negative
      multiple sclerosis were significantly less disabled than matched OCB positive
      controls. Re-examination of CSF-serum pairs from six OCB negative patients showed
      that three remained OCB negative while three showed evidence of intrathecal
      synthesis of OCBs. CONCLUSIONS: OCB negative clinically definite multiple
      sclerosis is rare and should be diagnosed with caution; in unequivocal cases it
      seems to have a relatively benign prognosis.

PMID- 8558145
TI  - Soluble E-selectin in multiple sclerosis: raised concentrations in patients with
      primary progressive disease.
AB  - OBJECTIVE: To determine whether concentrations of soluble E-selectin (sE
      selectin), an immunological marker of endothelial activation, were correlated
      with gadolinium-DPTA enhancement on MRI in patients with multiple sclerosis.
      METHODS: Serial sE-selectin concentrations were measured in 28 patients with
      multiple sclerosis undergoing monthly gadolinium (Gd) enhanced MRI of the brain
      and spinal cord, and in 10 control subjects. C reactive protein (CRP), von
      Willebrand factor (vWF), and tumour necrosis factor-alpha (TNF alpha) were also
      determined. RESULTS: Primary progressive patients had significantly increased sE
      selectin concentrations compared with the relapsing remitting and secondary
      progressive patients who had normal sE-selectin concentrations (22.2 (SD1 6.1)
      ng/ml v 9.8 (SD2.1) ng/ml and 7.7 (SD2.7) ng/ml, respectively, P = 0.03). This
      difference was attributable to five of the 10 primary progressive patients who
      had persistently raised sE-selectin concentrations, with relatively inactive MRI
      studies. No correlation could be found between sE-selectin concentrations and Gd
      enhancement on MRI, but a close correlation existed between mean concentrations
      of sE-selectin and TNF alpha (r = 0.71, P < 0.001). Despite raised sE-selectin
      and TNF alpha concentrations, primary progressive patients had normal CRP
      concentrations (1.03 (SD1.14) mg/l), which were significantly lower than the
      relapsing remitting (3.16 (SD2.54) mg/l) and secondary progressive patients (2.28
      (SD2.1) mg/l, P = 0.03). Raised CRP concentrations did correlate with infectious
      episodes, clinical relapse, and Gd enhancement, and were significantly raised
      when no MRI activity was found. Concentrations of vWF were normal in all patient
      groups. CONCLUSIONS: The results further high-light the differences between
      patients with primary progressive and those with relapsing remitting/secondary
      progressive multiple sclerosis.

PMID- 8558147
TI  - Paradoxical puborectalis contraction is a feature of constipation in patients
      with multiple sclerosis.
AB  - OBJECTIVE: To study the disturbed anorectal physiology associated with
      constipation in multiple sclerosis. METHODS: Anorectal function in 10 patients
      with clinically definite multiple sclerosis and constipation has been compared
      with 10 normal persons and 11 patients with idiopathic constipation, without
      multiple sclerosis. RESULTS: All 10 constipated patients with multiple sclerosis
      had difficulty evacuating barium paste during defaecography. In four of these
      there was complete failure of puborectalis relaxation when straining to
      defaecate, and in another four there was incomplete puborectalis relaxation.
      There was no evidence of lower motor neuron involvement of pelvic floor muscles
      in the multiple sclerosis group. CONCLUSIONS: Paradoxical puborectalis
      contraction is common in patients with multiple sclerosis in whom constipation is
      a symptom. This may be a feature of the disturbed voluntary sphincter control
      mechanism, analogous to detrusor sphincter dyssnergia in the bladder.

PMID- 8558148
TI  - Entacapone prolongs levodopa response in a one month double blind study in
      parkinsonian patients with levodopa related fluctuations.
AB  - OBJECTIVES: To establish, in a double blind manner, the antiparkinsonian effects
      of repeated dosing with entacapone, a peripheral COMT inhibitor. METHODS: A one
      month, cross over study was conducted. During the two four-week treatment
      periods, entacapone (200 mg) or placebo was given with each levodopa dose four to
      10 times daily. Motor responses were repeatedly quantified using the motor part
      of UPDRS. Plasma levodopa and its metabolites were measured. RESULTS: Entacapone
      prolonged the availability of levodopa in the plasma and thus to the brain by
      decreasing its peripheral O-methylation and slowing its elimination rate, without
      affecting the maximum plasma levodopa concentration or the time to maximum
      concentration. Corresponding with the pharmacokinetic findings, entacapone
      prolonged the duration of motor response to an individual levodopa/DDC inhibitor
      dose by 34 minutes (24%, P = 0.001) and dyskinesiae by 39 minutes (37%, P =
      0.002) compared with placebo, without affecting their magnitude or starting time.
      Entacapone treatment resulted in a reduction of 16% in the mean total daily
      levodopa dose due to dyskinesiae. Also, according to the home diaries, the mean
      daily "on" time increased by 2.1 hours compared with placebo, despite the lowered
      mean levodopa intake. CONCLUSION: The efficacy of repeated entacapone dosing as
      an adjuvant to levodopa/DDC inhibitor treatment for Parkinson's disease with
      levodopa related fluctuations is verified.

PMID- 8558150
TI  - Willow.

PMID- 8558149
TI  - Jaw movement dysfunction related to Parkinson's disease and partially modified by
      levodopa.
AB  - OBJECTIVES: To test the hypotheses that Parkinson's disease can differentially
      produce deficits in voluntary and rhythmic jaw movements, which involve different
      neuronal circuits, and that levodopa treatment improves specific components of
      the motor deficit. METHODS: Patients with idiopathic Parkinson's disease and
      control subjects were tested on a series of jaw motor tasks that included simple
      voluntary movement, isometric clenching, and natural and paced rhythmic
      movements. Jaw movements were measured by changes in electromagnetic fields and
      EMG activity. Patients with Parkinson's disease with fluctuations in motor
      responses to levodopa were tested while off and on. RESULTS: During the off
      state, patients with Parkinson's disease were significantly worse than the
      control subjects on most tasks. The deficits included a decrease in amplitude and
      velocity during jaw opening and closing, aberrant patterns and low amplitude of
      EMG activity during clenching, and low vertical amplitude and prolonged durations
      of occlusion during rhythmic movements. No decrements were found in the amplitude
      of voluntary lateral jaw movements or the frequency of rhythmic movements. During
      the on state, improvements occurred in the patterns and level of EMG activity
      during clenching and in the vertical amplitude and duration of occlusion during
      rhythmic movements, although a significant decrement occurred in the lateral
      excursion of the jaw. CONCLUSIONS: Parkinson's disease affects the central
      programming of functionally related muscles involved in voluntary and rhythmic
      jaw movements and levodopa replacement influences only certain aspects of jaw
      movement, most likely those requiring sensory feedback.

PMID- 8558151
TI  - Bent spine syndrome.
AB  - Eight elderly patients developed progressive paravertebral muscle weakness with
      bent spine on standing but normal supine posture. Computed tomography showed
      pronounced hypodensity of the paraspinal muscles. Serum creatine kinase was
      moderately increased, paraspinal EMG non-specific, and biopsy myopathic. The
      syndrome was familial in two patients and may be caused by a late onset
      paraspinal muscle dystrophy. In the absence of specific pathological changes,
      such cases could be classified as having "bent spine syndrome".

PMID- 8558152
TI  - Fibrocartilaginous embolism of the spinal cord: a clinical and pathogenetic
      reconsideration.
AB  - A 16 year old girl did a handstand for fun, returned to her feet, experienced a
      sudden pain in her back, and became progressively paraplegic within 30 hours. MRI
      showed lumbar cord swelling, multiple Schmorl's nodes, a collapsed T11-T12 disc
      space, and intraspongious disc prolapse into the T12 vertebral body. These
      findings, related to the initial manoeuvre, suggested that an acute vertical disc
      herniation could have occurred as the first step in a process leading to spinal
      cord infarction due to fibrocartilaginous emboli from the nucleus pulposus of the
      intervertebral disc. The medical literature so far reports 32 cases of
      fibrocartilaginous embolism (FCE) of the spinal cord, all at necropsy, with the
      exception of one histologically demonstrated in a living patient. A clinical
      diagnosis of FCE would be desirable for many important reasons, but was never
      made. This causes severe limitations in the knowledge of the disease and
      precludes any therapeutic possibility. On the basis of the clinical features and
      findings in the present case, compared with data from the reported cases, a first
      attempt is made to identify the clinical context within which new information
      obtainable through MRI examination can lead to a reliable clinical diagnosis of
      FCE. The vexed question of the pathogenesis has been reviewed. An increased
      intraosseous pressure within the vertebral body, due to acute vertical disc
      herniation, seems to offer a consistent pathogenetic explanation and some
      therapeutic prospects.

PMID- 8558153
TI  - Investigation of the neurogenic bladder.

PMID- 8558154
TI  - Post-traumatic syringomyelia (cystic myelopathy): a prospective study of 449
      patients with spinal cord injury.
AB  - OBJECTIVES: To assess the incidence of post-traumatic syringomyelia (PTS), to
      correlate the presence of PTS with its most common signs and symptoms, and to
      compare results from the Swiss Paraplegic Centre with those reported in the
      medical literature. METHODS: A total of 449 recent traumatic paraplegic and
      tetraplegic patients admitted to the Swiss Paraplegic Centre in Zurich between 1
      January 1987 and 31 December 1993 were prospectively analysed. Yearly clinical
      tests with conventional radiographs and additional T1 and T2 weighted images were
      performed as soon as PTS was diagnosed. RESULTS: Of these 449 patients 20
      patients displayed symptoms of PTS (4.45%). Ten non-operated patients remained
      clinically stable (average time: 37 months). Ten worsened--three refused
      operation, seven were operated on. Mean worsening time was 97 months.
      Deterioration was closely related to the enlargement of the cyst whereas in
      operated patients neurological improvement or stabilisation correlated with
      collapse of the cyst. CONCLUSIONS: Delay between appearance of the first symptoms
      of PTS and deterioration making surgery necessary may be long (mean five years in
      the seven operated patients) underlining the need for regular tests. "Slosh" and
      "suck" mechanisms could explain cyst enlargement as surgical realignment of the
      spine resulted in a complete cyst collapse in two of the operated patients
      (normalisation of CSF flow? ). Cord compression, tense syrinx at the fracture
      site, and kyphosis seemed to be closely linked to the enlargement of the cyst
      with subsequent further neurological deterioration.

PMID- 8558155
TI  - Benign paroxysmal positional vertigo of the horizontal canal.
AB  - OBJECTIVES: To review the clinical features, electronystagmography findings, the
      possible mechanism, and a possible therapeutic approach to benign paroxysmal
      positional vertigo (BPPV). METHODS: Sixty-three cases of BPPV of the horizontal
      canal type have been reviewed. It is characterised by horizontal nystagmus and an
      intense vertigo, provoked by rotation of the head in a supine patient. The
      horizontal nystagmus beats towards the ground on both sides, becomes more
      pronounced when lying on the pathological side, and then the nystagmus often
      changes direction. RESULTS: Forty-eight patients underwent electronystagmography.
      On the pathological side, the first phase nystagmus had a mean latency of three
      seconds and a mean duration of 31.6 seconds. Nystagmus inversion occurred in 36
      patients after a nystagmus free interval. The mean second phase nystagmus
      duration lasted 33.4 seconds. On the healthy side, the nystagmus had a mean
      latency of 3.4 seconds and a mean duration of 39.5 seconds. Fatigue was seen in
      six patients. Simultaneous involvement of the posterior canal was present in 16
      patients. A liberatory manoeuvre was successful in six patients. CONCLUSIONS: The
      liberatory manoeuvre should be tried in patients with horizontal canal vertigo.
      It should not be performed in patients with severe cervical arthrosis,
      vertebrobasilar insufficiency, or when the patient has neck pain during the
      manoeuvre.

PMID- 8558157
TI  - Neuropathological diagnosis and CAG repeat expansion in Huntington's disease.
AB  - OBJECTIVE: To correlate the degree of CAG repeat expansion with neuropathological
      findings in Huntington's disease. METHODS: The CAG repeat polymorphism was
      analysed in a large series of brain samples from 268 patients with a clinical
      diagnosis of Huntington's disease in which full neuropathological data was
      available. RESULTS: Analysis by polymerase chain reaction was successful in 63%
      of samples (169 of 268). Repeat expansions were detected in 152 of 153 (99%)
      samples with a neuropathological diagnosis of Huntington's disease. The
      exceptional case (22 CAG repeats) showed mild but definite pathological changes
      and had a typical clinical illness with a positive family history; it raises the
      possibility that an alternative mutation in the Huntington's disease gene may be
      responsible although it is more likely that a mutation in another gene has
      resulted in an Huntington's disease-like phenotype. Four of 16 cases without
      pathological changes of Huntington's disease also possessed an expanded repeat
      sequence; a glioblastoma masked the pathological changes of Huntington's disease
      in one case but the other three cases had a typical clinical history and a
      positive family history. These three cases may reliably be classified as
      Vonsattel's Huntington's disease grade 0. Three of 12 cases with a normal repeat
      length and no morphological changes of Huntington's disease showed other
      neuropathology; two had Alzheimer's disease and the other had multiple sclerosis.
      Review of the clinical notes of two other cases indicated a diagnosis of tardive
      dyskinesia complicating phenothiazine treatment of schizophrenia. The remaining
      pathology negative/expansion negative cases had been referred because of a family
      history of Huntington's disease; all but one were themselves symptom free. Apart
      from emphasising the possibility that an alternative mutation may result in a
      clinical phenocopy of Huntington's disease, this case suggests that such a
      clinical phenocopy may occur without gross or light microscopical
      neuropathological changes (Vonsattel's Huntington's disease grade 0).
      CONCLUSIONS: The study confirms the value of molecular genetic analysis in cases
      of suspected Huntington's disease and shows the importance of detailed
      neuropathological study in the few cases of suspected Huntington's disease with
      normal CAG repeat lengths.

PMID- 8558156
TI  - Hemifacial spasm: a prospective long-term follow up of 83 cases treated by
      microvascular decompression at two neurosurgical centres in the United Kingdom.
AB  - OBJECTIVE: To evaluate the use of microvascular decompression (MVD) for the
      treatment of hemifacial spasm (HFS). METHODS: Eighty three patients with HFS who
      underwent MVD via a suboccipital craniectomy are presented. RESULTS: Seventy two
      out of seventy eight patients available for follow up remained free of any spasms
      at a mean follow up period of eight years. Two patients continued to have minor
      intermittent muscle twitches and three had recurrence of HFS. One patient's
      operation was not completed. Twenty had a transient complication and eight were
      left with permanent postoperative deficits, the commonest being unilateral
      sensorineural deafness. Seventy one patients declared themselves satisfied with
      the procedure. A causative vessel was found on the root exit zone of the seventh
      cranial nerve in 81 patients. CONCLUSION: The procedure seems to provide lasting
      relief for most patients. The correct operative technique is essential if
      complications are to be avoided.

PMID- 8558158
TI  - Clinical application of electrophysiological markers in the differential
      diagnosis of depression and very mild Alzheimer's disease.
AB  - BACKGROUND: Current evidence indicates that, on their own, neither flash visual
      evoked responses (FVEPs) nor event related potentials (ERPs) are sufficiently
      useful to the clinician in the very early stages of memory dysfunction. However,
      the possibilities for the combined use of these measures has not been fully
      explored. METHODS: This study examined the clinical utility of combined FVEP and
      ERP-P300 component latencies as predictive markers in 16 patients with
      Alzheimer's disease, 15 patients with depression, and 21 control subjects.
      RESULTS: There were significant group differences in FVEP P2 latency (P = 0.004)
      between the controls and both the depressive patients and those with very mild
      Alzheimer's disease. There were no statistically significant group differences
      for the ERP component (N2/P300) amplitudes or latencies. The P300 component
      latency was positively correlated with both the FVEP N2 and FVEP P2 component
      latencies in the patients with Alzheimer's disease but not in the control
      subjects or the depressed patients. A discriminant function, using two ERP and
      two FVEP component measures, gave an overall correct classification rate for
      dementia of 78%. In this study of very mildly impaired patients the FVEP
      latencies provided a more sensitive marker for the presence of cognitive
      dysfunction than P300 latency delay. CONCLUSIONS: The findings support the use of
      multimodal evoked potentials in the differential diagnosis of very mild
      Alzheimer's disease and normal aging.

PMID- 8558160
TI  - Some Proustian doctors.

PMID- 8558159
TI  - Inflammatory demyelinating polyradiculitis in a patient with acute disseminated
      encephalomyelitis (ADEM).
AB  - A patient with severe acute disseminated encephalomyelitis died 12 days after the
      first symptom. Necropsy showed widespread severe demyelination in the CNS and
      some foci of demyelination in the spinal roots. The lesions in the peripheral
      nervous system were characterised by myelin stripping and the presence of
      macrophages, being severest in the spinal nerve roots. Some axons were completely
      demyelinated, whereas the axons themselves were preserved. Pathologically
      established ongoing demyelination in both CNS and peripheral nervous systems
      raises the possibility of a shared pathological epitope.

PMID- 8558161
TI  - Executive dysfunction in early Alzheimer's disease.
AB  - Twenty five patients with probable mild Alzheimer's disease were assessed for
      deficits in executive functioning and the impact of these deficits on performance
      in other neuropsychological domains. The Wisconsin card sorting test, the release
      from proactive interference paradigm, the verbal fluency test, and the Stroop
      test were adopted to classify patients with (AD+) and without (AD-) executive
      deficits. Seven of the patients showed an impairment in executive function (AD+),
      defined as a performance below the cut off score in at least two of these tests.
      There were no significant differences in clinical assessments, demographic
      features, or other cognitive functions between patients. Executive dysfunction
      may be an early additional feature in a subgroup of patients with mild
      Alzheimer's disease. Impairment on frontal lobe tests does not seem to be related
      to the severity or duration of disease, or to a different pattern of impairment
      in other cognitive domains.

PMID- 8558162
TI  - Impaired procedural learning after damage to the left supplementary motor area
      (SMA).
AB  - Two paradigms of procedural learning, serial reaction time and tracking tasks,
      were given to a patient with damage to the supplementary motor area (SMA) of the
      left mesiofrontal cortex. This patient exhibited impaired procedural learning
      during the serial reaction time test and mirror reversed tracking. Unreversed
      tracking performance was normal. Therefore the SMA--as well as the cerebellum and
      the striatum--participate in the development of skills requiring internal
      elaboration of motor behaviour.

PMID- 8558163
TI  - Signal changes on MRI and increases in reactive microgliosis, astrogliosis, and
      iron in the putamen of two patients with multiple system atrophy.
AB  - A correlation of clinical, MRI, and neuropathological data is reported in two
      patients with multiple system atrophy (MSA). On MRI, patient 1 showed striatal
      atrophy, reduction of T2 relaxation times within most of the putamen, and a band
      of hyperintense signal changes in the lateral putamen. In patient 2, MRI
      disclosed only shortening of the T2 signal in the putamen. Immunohistochemistry
      showed pronounced reactive microgliosis and astrogliosis in the affected brain
      regions. In patient 1, the area with the most pronounced microgliosis and
      astrogliosis most likely correlated with the area of hyperintense signal changes
      on MRI. This area also contained the highest amount of ferric iron, which was
      increased in the putamen of patient 1 but not patient 2. It is unlikely that the
      hypointense signal changes in the putamen are due to an increase of iron alone.
      Reactive microglial and astroglial cells may play a part in the pathogenesis of
      MSA.

PMID- 8558164
TI  - Current concepts of excitotoxicity.

PMID- 8558165
TI  - Brain myelinolysis following hypernatremia in rats.
AB  - Brain myelinolysis could develop after excessive correction (delta SNa > 20-25
      mEq/1/24 hour [h]) of chronic hyponatremia; however, this neurological event is
      not recognized as a complication of hypernatremia when arising from a
      normonatremic baseline. Previous animal studies were unable to reproduce these
      brain lesions in hypernatremia after acute increase of serum sodium to moderately
      hypernatremic levels. We hypothesize that to produce brain dehydration and
      myelinolysis from normonatremic baseline requires a more important osmotic
      gradient than when starting from hyponatremic state. Rapid and sustained
      hypernatremia (at least > 6 to 12 h) was induced in male rats by i.p.
      administration of NaCl 2 M (3 injections at 6 h intervals). The NaCl doses were
      determined to define two groups of hypernatremic rats (moderate and severe
      hypernatremia) for further analysis of the neurological outcome. In group 1
      (moderate hypernatremia, n = 26) 8 rats died early (< 12 h) after the beginning
      of the NaCl administration without specific neurologic manifestations. All the
      surviving rats fared well and were asymptomatic at time of death (day 8). They
      were submitted for at least 6 to 12 h to a serum sodium gradient of 28 +/- 6
      mEq/l. Brain analysis was normal in all of them without brain demyelinating
      lesions. In group 2 (n = 51), 24 rats also died rapidly (< 12 h). The surviving
      rats developed severe neurologic symptoms as typically encountered in
      hyponatremic rats with myelinolysis. The majority of them died before day 8. The
      hypernatremic gradient in this group was significantly higher than rats in group
      1 that completely recovered (mean delta SNa: 39 +/- 8 mEq/l, p < 0.001). In the 7
      surviving rats (mean delta SNa: 33 +/- 3 mEq/l) brain analysis demonstrated
      severe demyelinating lesions similar to the histologic changes observed in
      hyponatremia-related myelinolysis. We demonstrated for the first time that high
      and sustained levels of hypernatremia could induce brain myelinolysis and that
      the osmotic gradient necessary to produce brain lesions is higher for
      normonatremic than for hyponatremic rats.

PMID- 8558166
TI  - Developmental changes in [3H]lysergic acid diethylamide ([3H]LSD) binding to
      serotonin receptors in the human brainstem.
AB  - The ontogeny of serotonin receptors in the human brainstem is largely unknown,
      despite the putative roles of serotonin in neural development, synaptic
      transmission, brainstem modulation of vegetative functions, and clinical
      disorders of serotonergic function. This study provides baseline information
      about the quantitative distribution of [3H]LSD binding to serotonergic receptors
      (5-HT1A-1D, 5-HT2) in the human brainstem, from midgestation through maturity,
      with a focus upon early infancy. Brainstems were analyzed from 5 fetuses (19-25.5
      weeks postconception), 5 infants (42-55.5 weeks postconception), and 3 mature
      individuals (4, 20, and 52 years). Tissue autoradiography was used with [3H]LSD
      for total serotonergic receptor binding and [3H]LSD and serotonin for nonspecific
      binding; computer-based quantitation was applied. The highest levels of [3H]LSD
      binding occurred prenatally throughout the brainstem. At all ages, the highest
      relative binding localized to the rostral raphe. A marked decline in [3H]LSD
      binding occurred between the midgestation and infancy in brainstem regions
      involved in control of cardiovascular function, respiration, and pain. The fetal
      peak in [3H]LSD binding to 5-HT receptors is consistent with a trophic role of
      serotonin in immature human brainstem, and a decrease, between midgestation and
      infancy, in serotonergic modulation of vegetative functions controlled by the
      brainstem.

PMID- 8558167
TI  - Two types of senile plaque.

PMID- 8558168
TI  - Intracerebral targets and immunomodulation of murine Listeria monocytogenes
      meningoencephalitis.
AB  - In humans, infection with Listeria monocytogenes (L. monocytogenes) can severely
      affect the central nervous system (CNS). In the present study we have employed a
      murine model of CNS listeriosis to characterize the intracerebral distribution of
      L. monocytogenes. Following intracerebral application of a low dose of L.
      monocytogenes (serovar 1/2a, EGD strain) a severe fatal leptomeningitis,
      ventriculitis, and encephalitis developed. Listeria were detectable both
      intracellularly in different cell types of the CNS and extracellularly in the
      cerebrospinal fluid. Ultrastructural analysis revealed macrophages, granulocytes,
      plexus epithelial cells, ependymal cells, and neurons as target cells. An
      inflammatory reaction with macrophages and granulocytes developed in the brains
      of these animals but was not sufficient to prevent the fatal outcome of the
      disease. However, active immunization of mice prior to an intracerebral challenge
      infection significantly reduced the mortality. Immunized animals showed an early
      recruitment of a significant number of CD8+ and, to a lesser degree, CD4+ T cells
      within 24 hours p.i. as well as a strong activation of microglial cells and
      macrophages. These findings may provide an interesting model for studies on the
      pathogenesis of cerebral listeriosis.

PMID- 8558169
TI  - Alterations in nitrogen monoxide-synthesizing cortical neurons in amyotrophic
      lateral sclerosis with dementia.
AB  - Cognitive impairment in the absence of lesions indicative of Alzheimer's disease
      and other dementing conditions has long been recognized in a subgroup of patients
      with motor neuron disease MND), including amyotrophic lateral sclerosis. However,
      the mechanisms underlying this cognitive deterioration and its relationship with
      the relatively selective involvement of motor neurons remains elusive. We used
      histo- and immunocytochemical labeling methods to study the nitrogen monoxide
      (NO; a.k.a. nitric oxide) synthase (NOS)-/NADPH diaphorase-containing neurons
      (NOSN) in three patients with MND and dementia (MND+D), two patients with MND
      without dementia, and 19 controls that included patients with Alzheimer and non
      Alzheimer dementias. Patients with MND+D, but not those with MND without
      dementia, exhibit numerous dystrophic perikarya and neurites throughout all
      sensory, motor, association, and limbic neocortices examined. Interestingly,
      affected NOSN appear to correspond to some subtypes (smooth stellate and spiny
      neurons), while other neurons containing the same molecular phenotype (such as
      layer I local circuit neurons and layer II granule cells) are either spared or
      significantly less affected. These observations indicate that cognitive
      impairment and dementia in MND may be due, at least in part, to a pancortical
      involvement of certain types of NOSN. Consequently, the elucidation of the
      factors that make NOSN vulnerable in MND, and the prevention or pharmacological
      palliation of their loss, may eventually help to prevent or ameliorate cognitive
      impairment in MND and may also shed some light on the nature of the insult that
      targets motor neurons.

PMID- 8558170
TI  - H2O2 and nitric oxide-mediated oxidative stress induce apoptosis in rat skeletal
      muscle myoblasts.
AB  - In many degenerative and metabolic muscle diseases cells die without a marked
      inflammatory response. A potential mechanism how this could be accomplished is
      apoptotic cell death. Since there are no data available about apoptosis in cells
      of myogenic origin, we examined rat skeletal myoblasts for their potential to
      undergo apoptosis when exposed to reactive oxygen intermediates and nitric oxide.
      We observed morphologic changes typical for apoptotic cell death, and DNA
      fragmentation was confirmed by gel electrophoresis and molecular labeling assays.
      With these methods we could show that both reactive oxygen intermediates and
      nitric oxide can induce apoptosis in myoblasts in a dose-dependent manner. These
      results are discussed with regard to possible implications on the pathophysiology
      of various muscle diseases.

PMID- 8558171
TI  - Neocortical lewy body counts correlate with dementia in the Lewy body variant of
      Alzheimer's disease.
AB  - Patients with the Lewy body variant (LBV) of Alzheimer's disease (AD) meet
      diagnostic criteria for AD but have a lighter burden of plaque and tangle AD
      pathology despite comparable dementia. We quantified neocortical Lewy bodies (LB)
      in LBV patients (n = 14) using anti-ubiquitin polyclonal antibody, selecting for
      quantification those neocortical regions with the highest densities of LB.
      Neocortical neurofibrillary tangles (NFT) and neuritic plaques were evaluated
      with thioflavin- S. A group of classical AD patients (n = 12), matched for
      disease duration, was also studied. For most of these cases, entorhinal
      neurofibrillary pathology had previously been assessed by applying a modification
      of the Braak and Braak AD staging protocol. Although LBV and AD groups had
      similar mental test scores when last evaluated prior to death, lower neocortical
      NFT and plaque counts and lower modified Braak stages were observed in LBV.
      Neocortical NFT counts correlated with impaired neuropsychological test
      performance in AD but not in LBV. Plaque counts did not correlate with mental
      status in either group. Lewy body concentrations in four neocortical areas
      correlated significantly with dementia severity in LBV. The association of AD
      lesions in the neocortex with dementia in LBV was comparatively weaker than that
      observed for LB concentrations. These findings suggest that neocortical LB
      combined with entorhinal NFT or subcortical Parkinson's disease-type pathology
      may equalize the degree of dementia seen in LBV with that encountered in
      classical AD.

PMID- 8558172
TI  - Neuropathologic overlap of progressive supranuclear palsy, Pick's disease and
      corticobasal degeneration.
AB  - Several neurodegenerative disorders contain tau-immunoreactive neuronal and glial
      inclusions throughout the cerebral cortex and brainstem. Although these diseases
      have been considered distinct clinicopathological entities, recent recognition of
      many neuropathological and clinical parallels has raised the question of overlap
      between the disorders. In addition, histopathological similarities sometimes
      complicate neuropathological diagnosis. To address these issues, we examined the
      morphology and differential distribution of pathologic lesions in three
      disorders: progressive supranuclear palsy, Pick's disease, and corticobasal
      degeneration. We found considerable similarity in the anatomical regions affected
      by the three entities; however, semiquantitative analysis revealed differential
      anatomical susceptibility. Similarly, although overlap existed in the morphology
      of tau-immunoreactive inclusions, characteristic differences remained and may be
      useful in differential diagnosis. In particular, glial inclusions varied
      dramatically between the disorders. Despite significant overlap among the three
      neurodegenerative diseases examined, the morphological and regional differences
      suggest that each is a distinct pathophysiological entity.

PMID- 8558173
TI  - Cytoskeletal derangements of cortical neuronal processes three hours after
      traumatic brain injury in rats: an immunofluorescence study.
AB  - Semiquantitative Western blot analyses have shown that traumatic brain injury
      (TBI) can produce significant loss of cytoskeletal proteins (neurofilament 68
      [NF68], neurofilament 200 [NF200] and microtubule associated protein 2 [MAP2])
      possibly by calpain-mediated proteolysis. Thus, we employed immunofluorescence
      (light and confocal microscopy) to study the histopathological correlates of
      acute neurofilament and MAP2 protein decreases observed 3 hours following
      unilateral cortical injury in rats. TBI induced dramatic alterations in NF68,
      NF200, and MAP2 immunolabeling in dendrites within and beyond contusion sites
      ipsilateral and contralateral to the injury site. Marked changes in
      immunolabeling were associated with but not exclusively restricted to regions of
      dark shrunken neurons labeled by hematoxylin and eosin staining, a
      morphopathological response to injury suggesting impending cell death. Light
      microscopic studies of NF200 immunofluorescence revealed a prominent fragmented
      appearance of apical dendrites of pyramidal neurons within layers 3 and 5, as
      well as a loss of fine dendritic arborization within layer 1. Confocal microscopy
      detected varying degrees of NF200 disassembly associated with these areas of
      neurofilament fragmentation. Light microscopic studies of NF68 immunofluorescence
      detected subtle and less severe structural changes including smaller breaks and
      focal vacuolization of apical dendrites. Light microscopic immunofluorescence of
      MAP2 revealed changes similar to those seen for NF200. Acute axonal alterations
      detected with NF68 were minimal compared to immunofluorescence changes seen in
      dendritic regions. Therefore, preferential dendritic cytoskeletal derangements
      may be an early morphological feature of experimental traumatic brain injury in
      vivo. In addition, these cytoskeletal derangements may not be exclusively
      restricted to sites of contusion and cell death.

PMID- 8558174
TI  - Detection of complex genetic alterations in human glioblastoma multiforme using
      comparative genomic hybridization.
AB  - The aim of the present study was to detect complex genetic alterations in human
      glioblastoma multiforme (GBM) by comparative genomic in situ hybridization (CGH).
      Of the 24 GBM that were examined, increased fluorescence intensities indicating
      chromosomal polysomy of chromosome 7 and gene amplification at chromosome 7p were
      found in 42% of the tumors. In addition, signal enhancement of chromosome 19 was
      present in 29% and at 12q13-15 in 21% of the tumors. We also detected reduction
      of fluorescence intensities indicating gross deletions on chromosomes 10 (58%),
      9p (46%), and 13 (29%). There was a close correlation of CGH results when
      compared with Southern analysis of the EGFR gene localized on chromosome 7 and
      loss of heterozygosity detection of chromosome 9 and 10 by microsatellite PCR. A
      close correlation was also observed between copy number changes of chromosome 7
      and deletions of chromosome 10. Amplification of chromosome 12q and deletions of
      chromosomes 9p and 13 seemed to be complementary in the tumors investigated in
      the present study.

PMID- 8558175
TI  - Transfection of an invasive human astrocytoma cell line with a TIMP-1 cDNA:
      modulation of astrocytoma invasive potential.
AB  - Malignant astrocytomas are highly invasive tumors which infiltrate diffusely into
      regions of normal brain. The degradation of the extracellular matrix (ECM) by
      matrix metalloproteinases is thought to be one of the most important steps in the
      process of tumor invasion. However, the activity of most matrix
      metalloproteinases (MMPs) can be modulated by simultaneously secreted inhibitors
      (tissue inhibitors of metalloproteinases, TIMPs). We have previously shown that
      an imbalance between the levels of MMPs and TIMPs may be essential in the
      determination of the invasiveness of certain human malignant astrocytoma cell
      lines. To determine if the up-regulation of TIMP genes and gene products could
      modulate the invasiveness of human malignant astrocytoma cells, in the present
      study we have transfected a highly invasive astrocytoma cell line, SF-188, with
      an expression vector carrying a full-length TIMP-1 cDNA. The parental SF-188
      astrocytoma cell line overexpresses the 72-kDa and 92-kDa type IV collagenases
      with little expression of TIMPs-1 and -2. Following transfection with TIMP-1, SF
      188 astrocytoma clones expressed the 0.9 kb TIMP-1 message by northern analysis,
      and produced a 21 kDa metalloproteinase inhibitor by reverse zymography. The
      stable TIMP-1 SF-188 transformants demonstrated morphological changes and
      diminished growth rates in soft agar when compared to controls. The invasion of
      successfully TIMP-1 transfected astrocytoma cells across matrigel-coated filters
      was significantly decreased over controls. These results suggest that
      upregulation of TIMP-1 expression in SF-188 astrocytoma cells has decreased their
      in vitro invasive potential.

PMID- 8558176
TI  - Validity and reliability of the preliminary NINDS neuropathologic criteria for
      progressive supranuclear palsy and related disorders.
AB  - We investigated the validity and reliability of diagnoses made by eight
      neuropathologists who used the preliminary NINDS neuropathologic diagnostic
      criteria for progressive supranuclear palsy (PSP) and related disorders. The
      specific disorders were typical, atypical, and combined PSP, postencephalitic
      parkinsonism, corticobasal ganglionic degeneration, and Pick's disease. These
      disorders were chosen because of the difficulties in their neuropathologic
      differentiation. We assessed validity by measuring sensitivity and positive
      predictive value. Reliability was evaluated by measuring pairwise and group
      agreement. From a total of 62 histologic cases, each neuropathologist
      independently classified 16 to 19 cases for the pairwise analysis and 5 to 6
      cases for the group analysis. The neuropathologists were unaware of the study
      design, unfamiliar with the assigned cases, and initially had no clinical
      information about the cases. Our results showed that with routine sampling and
      staining methods, neuropathologic examination alone was not fully adequate for
      differentiating the disorders. The main difficulties were discriminating the
      subtypes of PSP and separating postencephalitic parkinsonism from PSP.
      Corticobasal ganglionic degeneration and Pick's disease were less difficult to
      distinguish from PSP. The addition of minimal clinical information contributed to
      the accuracy of the diagnosis. On the basis of results obtained, we propose
      clinicopathologic diagnostic criteria to improve on the NINDS criteria.

PMID- 8558177
TI  - Psychoeducational groups for young adults with genital herpes: training group
      facilitators.
AB  - Genital herpes is one of the sexually transmitted diseases that can have serious
      long-term psychological and physical consequences for young adults who contract
      the disease. Because of the chronic, reoccurring nature of genital herpes, these
      young adults need education about the transmission of the herpes virus and about
      safer sexual practices in addition to emotional support. Psychoeducational groups
      have shown to be a nursing intervention that can effectively provide this
      education and support. Yet community health nurses may not be knowledgeable about
      or comfortable with using this type of intervention. In this article we explain
      the process of training community health nurses to be nurse facilitators who
      conduct psychoeducational groups for young adults with genital herpes. The
      training consisted of a 1-day workshop and three follow-up sessions. The content
      and format of this training workshop and the follow-up sessions is presented in
      addition to recommendations to enhance this nursing intervention.

PMID- 8558178
TI  - Using a public health nursing model to assess and plan for health needs at a
      summer day camp.
AB  - The epidemiologic prevention process model (EPPM; Clark, 1992) was designed to
      guide community health nursing practice and research. The model incorporates
      epidemiologic, nursing, and public health perspectives and directs assessment of
      health needs and the planning, implementation, and evaluation of health care
      services at primary, secondary, and tertiary levels of prevention. The EPPM was
      used to assess needs for nursing services at a summer day camp and to plan to
      meet those needs. Assessment indicated that underlying factors in each of four
      components of the model (human biology, environment, lifestyle, and the health
      system) contributed to needs for nursing services. Assessment data were used to
      derive community nursing diagnoses and to plan interventions to meet identified
      health care needs. In this application, the EPPM was found to be an effective way
      of organizing and interpreting findings and of translating those findings into
      improved health care services in a camp setting.

PMID- 8558179
TI  - The lived experiences of homeless men.
AB  - To investigate the phenomenon of social disaffiliation in homeless men, a
      qualitative study was conducted that used a framework of Bahr's (1973) social
      disaffiliation theory. Ten homeless men were interviewed to determine their
      reasons for becoming homeless, their feelings about being homeless, and the
      specific resources they used for maintaining life on the streets. Using a
      semistructured interview, audiotapes were made of the responses of the 10 men, 20
      to 61 years old, who were using a shelter for the homeless in a U.S. southern
      city. For data analysis, Giorgi's phenomenological approach (cited in Omery,
      1983) was used. Activities and resources that the men used to meet their social,
      economic, and other needs were described. The following three major themes were
      identified: rejection, uncertainty, and social isolation. Recommendations include
      changing nursing curricula and conducting staff development programs, testing
      interventions to alleviate social isolation, and assisting the homeless to return
      to the societal mainstream.

PMID- 8558180
TI  - Evaluating a mental health education program for community health nurses.

PMID- 8558181
TI  - Nursing interventions classification: a content analysis of nursing activities in
      public schools.
AB  - Nursing Interventions Classification (NIC) is an effort to describe nursing
      activities by using a standardized nomenclature of nursing treatments (McCloskey
      & Bulechek, 1992). Limited research focused on community nursing activities has
      been included in the Iowa Intervention Project to date. The purpose of this study
      was to investigate how nursing activities performed by RN baccalaureate students
      in the public school setting conformed to the activities and interventions
      classifications proposed by the Iowa Intervention Project. Nursing activities
      were documented by 40 RNs for 1,774 clients in the schools. Those activities
      conformed to 25 of the 336 NICs. Findings further demonstrated that pain
      management was the most frequently used NIC, and patterns of clustering of
      classifications were also common. Although NIC can be used, the fit is not always
      strong. Specific recommendations are addressed for strengthening NIC use in the
      public schools.

PMID- 8558182
TI  - A critical skill for the future: community assessment.

PMID- 8558183
TI  - Finally, a successful adjuvant therapy for high-risk melanoma.

PMID- 8558184
TI  - Graphs to estimate an individualized risk of breast cancer.
AB  - PURPOSE: Clinicians who counsel women about their risk for developing breast
      cancer need a rapid method to estimate individualized risk (absolute risk), as
      well as the confidence limits around that point. The Breast Cancer Detection
      Demonstration Project (BCDDP) model (sometimes called the Gail model) assumes no
      genetic model and simultaneously incorporates five risk factors, but involves
      cumbersome calculations and interpolations. This report provides graphs to
      estimate the absolute risk of breast cancer from the BCDDP model. PATIENTS AND
      METHODS: The BCDDP recruited 280,000 women from 1973 to 1980 who were monitored
      for 5 years. From this cohort, 2,852 white women developed breast cancer and
      3,146 controls were selected, all with complete risk-factor information. The
      BCDDP model, previously developed from these data, was used to prepare graphs
      that relate a specific summary relative-risk estimate to the absolute risk of
      developing breast cancer over intervals of 10, 20, and 30 years. RESULTS: Once a
      summary relative risk is calculated, the appropriate graph is chosen that shows
      the 10-, 20-, or 30-year absolute risk of developing breast cancer. A separate
      graph gives the 95% confidence limits around the point estimate of absolute risk.
      Once a clinician rules out a single gene trait that predisposes to breast cancer
      and elicits information on age and four risk factors, the tables and figures
      permit an estimation of a women's absolute risk of developing breast cancer in
      the next three decades. CONCLUSION: These results are intended to be applied to
      women who undergo regular screening. They should be used only in a formal
      counseling program to maximize a woman's understanding of the estimates and the
      proper use of them.

PMID- 8558185
TI  - Pretreatment serum squamous cell carcinoma antigen: a newly identified prognostic
      factor in early-stage cervical carcinoma.
AB  - PURPOSE: To investigate the prognostic value of pretreatment serum squamous cell
      carcinoma antigen (SCC-ag) levels in patients with cervical squamous cell
      carcinoma in relation to well-established conventional risk factors. PATIENTS AND
      METHODS: Sera from 653 women treated for squamous cervical cancer between 1978
      and 1994 were analyzed for the presence of SCC-ag and related to
      clinicopathologic characteristics and patient outcome using univariate and
      multivariate analyses. RESULTS: Increased pretreatment SCC-ag levels correlated
      strongly with unfavorable clinicopathologic characteristics (International
      Federation of Gynecology and Obstetrics [FIGO] stages IB to IV [P < or = .00005];
      stages IB and IIA: tumor size [P = .0236], deep stromal infiltration [P =
      .00009], and lymph node metastasis [P = .0001]). After multivariate analysis,
      elevated pretreatment serum SCC-ag levels (P = .001), lesion size (P = .043), and
      vascular invasion by tumor cells (P = .001) were independent predictors for the
      presence of lymph node metastases. In Cox regression analysis, controlling for
      SCC-ag, lesion size, grade, vascular invasion, depth of stromal infiltration, and
      lymph node status only the initial SCC-ag level had a significant independent
      effect on survival (P = .0152). Even in node-negative patients, the risk of
      recurrence was three times higher if the SCC-ag level was elevated before
      therapy. CONCLUSION: The determination of pretreatment serum SCC-ag level
      provides a new prognostic factor in early-stage disease, particularly in patients
      with small tumor size. In future trials to assess the value of new treatment
      strategies, pretreatment serum SCC-ag levels can be used to help identify
      patients with a poor prognosis.

PMID- 8558186
TI  - Neoadjuvant combined modality program with selective organ preservation for
      invasive bladder cancer: results of Radiation Therapy Oncology Group phase II
      trial 8802.
AB  - PURPOSE: This phase II study was designed to evaluate effectiveness and toxicity
      of a combined chemoradiotherapy program with selective bladder preservation in
      the management of patients with invasive bladder cancer. PATIENTS AND METHODS:
      Ninety-one eligible patients with invasive bladder cancer stages T2M0 to T4AM0
      suitable for radical cystectomy received two courses of methotrexate, cisplatin,
      and vinblastine (MCV regimen) followed by radiotherapy with 39.6 Gy and
      concurrent cisplatin. After complete urologic evaluation, operable patients who
      achieved complete response were selected for bladder preservation and treated
      with consolidation cisplatin-radiotherapy. RESULTS: Of 91 eligible patients, 85
      underwent complete urologic evaluation and 68 (75%; 95% confidence interval [CI],
      59% to 84%) had documented complete responses. Fourteen operable patients with
      residual tumor underwent immediate cystectomy. Of 70 patients treated with
      consolidation cisplatin-radiotherapy, 36 subsequently developed bladder
      recurrences, 23 of which were invasive. Patients with invasive recurrence (n =
      16), extensive noninvasive recurrence (n = 6), or severe treatment complications
      (n = 1) underwent salvage cystectomy. Thus, a total of 37 of 91 patients (40%)
      required cystectomy. The 4-year cumulative risk of invasive local failure (which
      includes induction failures) was 43% (95% CI, 33% to 53%). The 4-year actuarial
      risk of distant metastasis was 22% (95% CI, 13% to 31%). The 4-year actuarial
      survival rate of the entire group was 62% (95% CI, 52% to 72%). The 4-year
      actuarial rate of survival with bladder intact was 44% (95% CI, 34% to 54%).
      CONCLUSION: Initial results of this combined chemoradiotherapy program show that
      bladder preservation can be achieved in the majority of patients, and that
      overall survival is similar to that reported with aggressive surgical approaches.
      Long-term survival and quality-of-life assessments require longer follow-up
      study.

PMID- 8558187
TI  - Two schedules of teniposide with or without cisplatin in advanced non-small-cell
      lung cancer: a randomized study of the European Organization for Research and
      Treatment of Cancer Lung Cancer Cooperative Group.
AB  - PURPOSE: We conducted a randomized trial to investigate the value of the addition
      of cisplatin to teniposide (VM26) and to investigate the schedule dependence of
      the topoisomerase II inhibitor VM26, in advanced non-small-cell lung cancer
      (NSCLC) patients. PATIENTS AND METHODS: Two hundred twenty-five NSCLC patients
      were randomized to receive VM26 120 mg/m2 on days 1, 3, and 5 or 360 mg/m2 on day
      1 only, either as a single drug or in combination with cisplatin 80 mg/m2 on day
      1. Cycles were repeated every 3 weeks. Response rates, side effects, and survival
      were compared according to the 2 x 2 factorial design of this study. RESULTS: The
      response rate of the two cisplatin-containing arms was superior to that of the
      two arms that contained VM26 only (22% v 6%, P < .001); progression-free survival
      and survival times were also longer in the cisplatin-containing arms (median, 4.3
      v 2.2 months, P = .003; median 7.2 v 5.9 months, P = .008, respectively).
      Toxicity was significantly higher in the cisplatin-containing arms; the most
      frequent side effects were leukopenia, nausea and vomiting, and alopecia. The
      schedule of VM26 did not significantly influence the response rate, progression
      free survival interval, or survival duration. However, the response rate of the 1
      day administration was significantly lower than that of the 3-day administration
      when given as single drugs. CONCLUSION: The addition of cisplatin to VM26
      improves the response rate, progression-free survival interval, and survival
      duration over VM26 alone, although at the cost of a significant increase in
      toxicity. Cisplatin should be considered as the basis for combination
      chemotherapies in advanced NSCLC.

PMID- 8558188
TI  - Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus
      megestrol acetate/placebo in extensive-stage small-cell lung cancer: a North
      Central Cancer Treatment Group study.
AB  - PURPOSE: Megestrol acetate has been reported to improve appetite and quality of
      life and to decrease nausea and vomiting in patients with cancer
      anorexia/cachexia. The present trial was formulated to evaluate the impact of
      megestrol acetate on quality of life, toxicity, response, and survival in
      individuals with extensive-stage small-cell lung cancer who received concomitant
      chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive megestrol
      acetate 800 mg/d orally or placebo. In addition, all patients were scheduled to
      receive a maximum of four cycles of cisplatin and etoposide chemotherapy. Quality
      of life was self-assessed at entry onto study, with every cycle of chemotherapy,
      and 4 months thereafter with a linear visual analog scale. Toxicity was evaluated
      by patient questionnaire and investigator reports. RESULTS: A total of 243
      eligible patients were randomized. Those who received megestrol acetate had
      increased nonfluid weight gain (P = .004) and significantly less nausea (P =
      .0002) and vomiting (P = .02). Significant thromboembolic phenomena occurred more
      often in patients who received megestrol acetate versus placebo (9% v 2%, P =
      .01). Patients who received megestrol acetate had more edema (30% v 20%, P =
      .002), an inferior response rate to chemotherapy (68% v 80%, P = .03), and a
      trend for inferior survival duration (median, 8.2 v 10.0 months, P = .49). These
      findings may have been influenced by a poorer quality of life of the megestrol
      acetate group at study initiation. There were no significant changes in quality
      of life scores over time between either of the study arms. CONCLUSION: Megestrol
      acetate cannot be routinely recommended for all patients with small-cell lung
      cancer at the time of chemotherapy initiation. Rather, its therapeutic ratio may
      be more favorable for patients with problematic cancer anorexia/cachexia.

PMID- 8558189
TI  - Phase II trial of a 3-hour infusion of paclitaxel in previously untreated
      patients with advanced non-small-cell lung cancer.
AB  - PURPOSE: To determine the antitumor activity and toxicity of paclitaxel
      administered as a 3-hour infusion in patients with advanced non-small-cell lung
      cancer (NSCLC). PATIENTS AND METHODS: Fifty-one patients with advanced measurable
      or assessable NSCLC and performance status 0 to 2 who had not received prior
      chemotherapy were treated with paclitaxel 175 mg/m2 over 3 hours with
      premedication. Cycles were repeated every 3 weeks for a maximum of nine cycles.
      Most patients had prior radiotherapy (57%), extrathoracic metastatic disease
      (65%), and measurable disease (75%). Twenty-two percent had previously untreated
      stage III disease. RESULTS: The objective response rate was five of 51 (10%; 95%
      confidence interval, 3% to 21%). No subgroup with a higher response rate could be
      identified. There were no complete responses (CRs) and all responses lasted less
      than 5 months. Treatment was well tolerated with brief World Health Organization
      (WHO) grade IV neutropenia in only 16% of patients. Grade III/IV
      myalgia/athralgia occurred in 22% of patients. No significant hypersensitivity
      reactions occurred. CONCLUSION: The antitumor activity of this dose and schedule
      appears inferior to that reported in previously published phase II trials in
      NSCLC that used higher doses of paclitaxel infused over 24 hours, although
      confidence intervals for response overlap. Determining the optimal dose and
      schedule for using paclitaxel in NSCLC requires further investigation, and these
      results should caution against using shorter infusions outside appropriate
      clinical trials.

PMID- 8558190
TI  - Neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for
      squamous cell carcinoma of the esophagus: a preliminary analysis of the phase II
      intergroup trial 0122.
AB  - PURPOSE: To determine the preliminary acute toxicity and survival results of
      neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose
      radiation therapy in patients with local/regional squamous cell carcinoma of the
      esophagus. MATERIALS AND METHODS: Forty-five patients with clinical stage T1-4N0
      1M0 squamous cell carcinoma were entered onto the trial. Eight patients were
      declared ineligible after registration. Patients received three monthly cycles of
      fluorouracil (5-FU; 1,000 mg/m2/24hr for 5 days) and cisplatin (100 mg/m2 on day
      1) (neoadjuvant segment) followed by two additional monthly cycles of 5-FU (1,000
      mg/m2/24hr for 5 days) and cisplatin (75 mg/m2 on day 1) plus concurrent 64.8 Gy
      (combined modality segment). RESULTS: With a median follow-up of 15 months in
      surviving patients, the incidence of total grade 3+ toxicity during the
      neoadjuvant chemotherapy segment was 61%, and during the combined modality
      segment was 72%. Of the 33 patients who started radiation therapy, 91% were able
      to complete the full course. There were six deaths during treatment, five of
      which (11%), because of nadir sepsis and/or dehydration, were treatment-related.
      For the 37 eligible patients, the median disease-free survival duration was 9
      months, and the overall median survival was 20 months. CONCLUSION: The
      preliminary analysis of this trial demonstrated that the incidence of grade 3+
      toxicity was similar to that reported in the combined modality arm of the prior
      Radiation Therapy Oncology Group (RTOG) intergroup esophageal trial RTOG 85-01.
      However, because of the increased incidence of treatment-related mortality, this
      treatment program will not be used as an experimental arm of intergroup trial INT
      0123 (RTOG 94-05).

PMID- 8558191
TI  - Concurrent radiation therapy and chemotherapy followed by esophagectomy for
      localized esophageal carcinoma.
AB  - PURPOSE: A prospective study was performed to determine the outcome of patients
      with esophageal cancer who received preoperative radiation therapy and
      chemotherapy followed by esophagectomy, and to determine the role of preresection
      esophagogastroduodenoscopy (EGD) in predicting the patients in whom surgery could
      possibly be omitted, and the impact of surgery on survival. MATERIALS AND
      METHODS: Thirty-five patients with localized carcinoma of the esophagus received
      concurrent external-beam radiotherapy and chemotherapy followed by esophagectomy.
      Patients received 45 Gy in 25 fractions. Chemotherapy consisted of continuous
      infusion fluorouracil (5-FU; 1,000 mg/m2/d) on days 1 through 4 and 29 through 32
      and cisplatin (100 mg/m2) on day 1. Patients underwent an Ivor-Lewis
      esophagectomy 18 to 33 days after completion of radiotherapy. RESULTS: Eighty
      percent of the patients had squamous cell carcinoma and 20% had adenocarcinoma.
      In addition, 51% had a pathologic complete response (CR). Twenty-two of the 35
      underwent a preresection EGD before resection. Seventeen of the 22 (77%) had
      negative pathology from the preresection EGD, but seven of the 17 (41%) had
      residual tumor at surgery. The median survival and disease-free survival rates
      for all patients were 25.8 months and 32.8 months, respectively. Eighteen
      patients (51%) had no tumor at resection. The median survival for these patients
      was 36.8 months; the median disease-free survival time has not been reached. The
      median survival and disease-free survival rate for the patients with residual
      tumor in the surgical specimen were 12.9 months and 10.8 months, respectively.
      CONCLUSION: Preresection EGD is not reliable for determining the presence of
      residual disease or the patients in whom surgery could be omitted. Twenty-five
      percent of the patients with residual tumor in the resected surgical specimen
      were long-term survivors; this suggests a benefit from esophagectomy after
      concurrent radiotherapy and chemotherapy.

PMID- 8558192
TI  - Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma.
      European Organization for Research and Treatment of Cancer Gastrointestinal Treat
      Cancer Cooperative Group.
AB  - PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB)
      administered as a single agent in metastatic squamous cell esophageal carcinoma.
      PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were
      included and were stratified according to previous chemotherapy. Thirty patients
      without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy
      were assessable for toxicity and response. VNB was administered weekly as a 25
      mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%)
      without prior chemotherapy achieved a partial response (PR) (95% confidence
      interval [CI], 8% to 39%). The median duration of response was 21 weeks (range,
      17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete
      response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response
      rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI,
      6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well
      tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At
      least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A
      grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred.
      Other side effects were rare, and peripheral neurotoxicity has been minor (26%
      grade 1). CONCLUSION: These data indicate that VNB is an active agent in
      metastatic esophageal squamous cell carcinoma. Given its excellent tolerance
      profile and low toxicity, further evaluation of VNB in combination therapy is
      warranted.

PMID- 8558193
TI  - Relation between tumor size, quality of life, and survival in patients with
      colorectal liver metastases.
AB  - PURPOSE AND METHODS: This study assessed the relationship between survival, tumor
      size, and quality of life (QoL; Rotterdam Symptom Checklist [RSC], Hospital
      Anxiety and Depression Scale [HAD], and Sickness Impact Profile [SIP]) in 50
      patients with colorectal liver metastases (CLM). RESULTS: Physical symptom score
      (RSC) was a stronger survival predictor than tumor size measured on computed
      tomographic (CT) scan. The best model for predicting survival included QoL
      questions about diarrhea, eating, restlessness, and ability to work and sleep.
      The only clinically measured variable included in this best survival prediction
      model was serum alkaline phosphatase level. This is the first study to show that
      QoL indices predict survival in CLM. The findings suggest that differences in
      tumor products and not just in tumor size could influence patient fitness and
      survival in CLM. Such differences are more accurately estimated by QoL assessment
      than measurement of tumor size. CONCLUSION: QoL provides a better survival
      estimate than measurement of tumor size and could be used as a surrogate end
      point for survival in treatment trials.

PMID- 8558194
TI  - Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for
      primary tumor response and overall survival.
AB  - PURPOSE: We tested the hypothesis that polymerase chain reaction (PCR)
      quantitation of the enzyme thymidylate synthase (TS) within a primary
      adenocarcinoma of the stomach, has an inverse relationship to response and
      survival for patients who receive fluorouracil (5FU)-based chemotherapy. PATIENTS
      AND METHODS: Before systemic chemotherapy, the genetic expression of TS (TSmRNA
      level) was determined using a PCR method. Gene expression was calculated by
      determining the ratio between the amount of radiolabeled PCR product with the
      linear amplification range of the TS gene and the beta-actin gene. Chemotherapy
      consisted of two cycles of protracted infusion (PI) 5FU 200 mg/m2/d administered
      for 3 weeks with leucovorin 20 mg/m2/w. Cisplatin 100 mg/m2 was administered on
      day 1. RESULTS: Sixty-five patients with primary gastric cancer had a median TS
      mRNA level of 4.6 x 10(-3) (range, 0.9 to 20.1 x 10(-3)). Thirty-five percent of
      patients had measurable responses in their primary tumors. The mean gastric
      cancer TSmRNA level in responding and resistant patients is statistically
      significant (P < .001). The median survival time was 43+ months for treated
      patients with TSmRNA levels less than the median and 6 months for those with TS m
      RNA levels greater than the median (P = .003). CONCLUSION: The genetic expression
      of TS (TSmRNA level) influences response to 5FU-based chemotherapy and survival
      for a cohort of patients with primary gastric cancer. Confirmation of these data
      could lead to therapeutic decisions based on specific molecular properties within
      a tumor.

PMID- 8558196
TI  - Geographic variation in patient surveillance after colon cancer surgery.
AB  - PURPOSE: Considerable variation among surgeons exists in the current practice of
      patient surveillance after colon cancer treatment. We evaluated whether
      geographic factors are responsible for this observed variation. METHODS: Profiles
      of hypothetical patients and a detailed questionnaire based on the profiles were
      mailed to 2,733 members of two national surgical societies. The influence of the
      geographic location of the respondents on practice patterns were assessed in two
      ways. Repeated-measures analysis of variance was used to compare the practice
      patterns among 19 large metropolitan statistical areas (MSAs) and chi 2 analysis
      was used to determine whether these patterns differed by MSA population size.
      RESULTS: Seven of nine commonly used surveillance modalities were ordered
      significantly more frequently with increasing tumor-node-metastasis (TNM) stage
      and significantly less frequently with year postsurgery among the 995 respondents
      with assessable responses, but MSA population size and geographic location of
      physicians generally had no effect on documented practice variability. The
      remaining two modalities (bone scan and computed tomography [CT]) were used so
      infrequently as to preclude meaningful analysis. CONCLUSION: Surveillance after
      potentially curative colon cancer surgery for otherwise healthy patients is not
      significantly affected by the geographic location of the surgeon who performs the
      surveillance testing and only modestly affected by the population size of the MSA
      in which he/she practices. These data should help in the design of prospective
      trials of this topic.

PMID- 8558195
TI  - Uniform approach to risk classification and treatment assignment for children
      with acute lymphoblastic leukemia.
AB  - PURPOSE: To define more uniform criteria for risk-based treatment assignment for
      children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation
      Program (CTEP) of the National Cancer Institute (NCI) sponsored a workshop in
      September 1993. Participants included representatives from the Childrens Cancer
      Group (CCG), Pediatric Oncology Group (POG), Dana-Farber Cancer Institute (DFCI),
      St Jude Children's Research Hospital (SJCRH), and the CTEP. METHODS: Workshop
      participants presented and reviewed data from ALL clinical trials, using weighted
      averages to combine outcome data from different groups. RESULTS: For patients
      with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event
      free survival [EFS] rate, approximately 80%) will include patients 1 to 9 years
      of age with a WBC count at diagnosis less than 50,000/microL. The remaining
      patients will be classified as having high-risk ALL (4-year EFS rate,
      approximately 65%). For patients with T-cell ALL, different treatment strategies
      have yielded different conclusions concerning the prognostic significance of T
      cell immunophenotype. Therefore, some groups/institutions will classify patients
      with T-cell ALL as high risk, while others will assign risk for patients with T
      cell ALL based on the uniform age/WBC count criteria. Workshop participants
      agreed that the risk category of a patient may be modified by prognostic factors
      in addition to age and WBC count criteria, and that a common set of prognostic
      factors should be uniformly obtained, including DNA index (DI), cytogenetics,
      early response to treatment (eg, day-14 bone marrow), immunophenotype, and CNS
      status. CONCLUSIONS: The more uniform approach to risk-based treatment assignment
      and to collection of specific prognostic factors should increase the efficiency
      of future ALL clinical research.

PMID- 8558197
TI  - Dose-escalation trial of cladribine using five daily intravenous infusions in
      patients with advanced hematologic malignancies.
AB  - PURPOSE: The optimal dose and schedule for cladribine (2CdA) therapy of malignant
      hematologic diseases have not been determined. This dose-escalation study was
      designed to assess toxicity when 2CdA is given using five daily 1-hour
      intravenous infusions. PATIENTS AND METHODS: Forty-two adults with advanced
      hematologic malignancies were treated in one of nine cohorts, starting at 2.5
      mg/m2/d for 5 days. Plasma drug concentrations were measured by high-performance
      liquid chromatography. Responses were assessed by bone marrow biopsy on day 15 of
      the first course and by clinical measurements after each course. Patients
      received one to four courses each. RESULTS: Nonhematologic toxicity was mild, and
      dose-limiting nonhematologic toxicity was not observed, even at the highest dose
      level of 21.5 mg/m2/d. In particular, neurotoxicity was not observed. The maximum
      tolerated dose (MTD) was not identified. However, prolonged cytopenias and severe
      infections were more common in the higher 2CdA dose cohorts. Logistic regression
      analysis suggested that severe hematologic toxicity was associated with
      pretreatment platelet count and performance status (PS). Good-risk patients were
      identified as having a PS of 0 and platelet count > or = 80,000/microL, PS of 1
      and platelet count > or = 120,000/microL, or PS of 2 and platelet count > or =
      160,000/microL. Sustained complete responses (CRs) and partial responses (PRs)
      were observed in eight patients. CONCLUSION: 2CdA can be administered using five
      daily 1-hour infusions at 21.5 mg/m2/d without dose-limiting nonhematologic
      toxicity. Unlike continuous intravenous infusions, neurotoxicity was not observed
      using this schedule. Further dose escalation may be possible in good PS patients
      with adequate platelet counts.

PMID- 8558198
TI  - Significance of cytogenetic clonal evolution in chronic myelogenous leukemia.
AB  - PURPOSE: To describe the incidence and significance of clonal evolution patterns.
      PATIENTS AND METHODS: We analyzed 264 patients with Philadelphia chromosome (Ph)
      positive chronic myelogenous leukemia (CML) who developed clonal evolution
      between 1967 and 1993. RESULTS: The median survival time following clonal
      evolution was 19 months. Factors associated with worse survival (P < .01) were as
      follows: chromosome 17 abnormality or chromosomal translocations other than Ph,
      high percentage of abnormal metaphases, longer time to clonal evolution, and
      presence of other accelerated-phase features. A recursive partitioning technique
      (CART) identified different risk groups. The best group (37 patients; no
      chromosome 17 abnormality, abnormal metaphases < 16%, and interval to clonal
      evolution < or = 24 months) had an estimated median survival time of 54 months.
      The worst two groups included 27 patients with chromosome 17 abnormalities and >
      or = 36% abnormal metaphases (estimated median survival time, 6 months), and 22
      patients with other accelerated features and > or = 16% abnormal metaphases
      (estimated median survival time, 7 months). The intermediate group had an
      estimated median survival time that ranged from 13 to 24 months. Prior interferon
      therapy evaluated within risk groups showed a significant survival advantage only
      in the intermediate-risk group. A multivariate analysis showed similar results,
      and identified the following independent poor prognostic variables: chromosome 17
      abnormality, percentage of abnormal metaphases (cutoff, 24%), longer time to
      clonal evolution (cutoff, 24 months), other accelerated-phase features, and no
      prior interferon therapy. Patients with none, one, two, three, or more of the
      first four features had median survivals times of 51, 24, 14, and 7 months,
      respectively. CONCLUSION: The prognostic significance of clonal evolution in CML
      is not uniform and is related to the specific abnormality, time to its
      development, its predominance in metaphases, and the presence of other
      accelerated features, and it may be modified by specific therapies.

PMID- 8558199
TI  - Randomized trials between behenoyl cytarabine and cytarabine in combination
      induction and consolidation therapy, and with or without ubenimex after
      maintenance/intensification therapy in adult acute myeloid leukemia. The Japan
      Leukemia Study Group.
AB  - PURPOSE: We analyzed complete remission (CR), disease-free survival (DFS), and
      event-free survival (EFS) rates in two groups of patients treated with either N4
      behenoyl-1-beta-D-arabinosylcytosine (BHAC) or cytarabine, and analyzed DFS with
      or without ubenimex, a biologic response modifier. PATIENTS AND METHODS: Newly
      diagnosed patients with acute myeloid leukemia (AML) were randomized to receive
      either BHAC or cytarabine as remission-induction combination chemotherapy and two
      courses of consolidation therapy. After maintenance/intensification therapy,
      patients in CR were randomized to receive either ubenimex and no drug. RESULTS:
      Of 341 patients registered, 326 were assessable. The age of assessable patients
      ranged from 15 to 82 years (median, 48). The overall CR rate was 77%: 72% in the
      BHAC group and 81% in the cytarabine group, and there was a significant
      difference between the two groups (P = .035, chi 2 test). The predicted 55-month
      EFS rate of all patients was 30%: 23% in the BHAC group and 35% in the cytarabine
      group, with a significant difference between groups (P = .0253). The predicted 55
      month DFS rate of all CR patients was 38% and that of CR patients less than 50
      years of age was 47%. There was no significant difference in DFS between the
      ubenimex group and the group that did not receive ubenimex. CONCLUSION: Analyses
      of our clinical trial showed that the use of BHAC in remission-induction therapy
      and in consolidation therapy resulted in poorer CR and EFS rates in adult AML
      patients compared with the use of cytarabine at the doses and schedules tested.
      Immunotherapy with ubenimex after the end of all chemotherapy did not improve
      DFS.

PMID- 8558200
TI  - Outcome of high-dose therapy and autologous transplantation in non-Hodgkin's
      lymphoma based on the presence of tumor in the marrow or infused hematopoietic
      harvest.
AB  - PURPOSE: To evaluate the outcomes in 65 consecutive patients with non-Hodgkin's
      lymphoma (NHL) undergoing high-dose therapy (HDT) and autologous transplantation
      based on initial marrow involvement and the presence or absence of minimal
      disease in the hematopoietic harvests. PATIENTS AND METHODS: Patients with any
      history of histologic evidence of marrow tumor underwent autologous peripheral
      blood stem-cell transplantation (PSCT), whereas others underwent autologous bone
      marrow transplantation (ABMT). Patients who underwent ABMT were further
      segregated retrospectively into two groups depending on whether there was
      evidence by cell culture and/or Southern analysis of minimal tumor in the marrow
      harvest. RESULTS: Comparable proportions (58% to 60%) of patients in each of the
      two groups (PSCT and ABMT) achieved a complete clinical remission (CR) at 100
      days. For patients who achieve a CR, the actuarial relapse-free survival rate at
      5 years for PSCT patients who received a tumor-negative apheresis harvest was
      64%, compared with 57% for patients who received a tumor-negative bone marrow
      harvest and 17% for patients who received a histologically negative but minimally
      contaminated bone marrow harvest. Lymphoma grade and phenotype were not
      significant predictors of outcome. CONCLUSION: The observation that survival was
      significantly better in the groups of patients who received tumor-negative
      harvests and worse for patients who received minimally contaminated harvests
      suggests that tumor cells, even at minimal levels, reinfused in the transplanted
      harvest are responsible for progression in a proportion of patients who achieve a
      CR following HDT, although other biologic characteristics of the tumor could also
      be important. A relatively good outcome can be achieved with HDT and PSCT, even
      in patients with a significant marrow tumor burden.

PMID- 8558201
TI  - Allogeneic marrow transplantation for myelodysplastic syndrome with advanced
      disease morphology: a phase II study of busulfan, cyclophosphamide, and total
      body irradiation and analysis of prognostic factors.
AB  - PURPOSE: To determine if an intensive preparative regimen of busulfan (BU),
      cyclophosphamide (CY), and total-body irradiation (TBI) could improve outcome
      after marrow transplantation for advanced morphology myelodysplasia (refractory
      anemia with excess blasts [RAEB], RAEB in transformation [RAEB-T], and chronic
      myelomonocytic leukemia [CMML]) compared with that obtained with conventional
      CY/TBI and to analyze prognostic factors for transplantation for myelodysplasia.
      PATIENTS AND METHODS: A phase II study was conducted of 31 patients (median age,
      41 years) treated with BU (7 mg/kg), CY (50 mg/kg), TBI (12 Gy), and human
      leukocyte antigen (HLA)-matched (n = 23) or -mismatched (n = 2) related or
      unrelated donor (n = 6) marrow transplantation. Results were compared with 44
      historical control patients treated with CY (120 mg/kg) and TBI. RESULTS: The 3
      year actuarial disease-free survival (DFS) rate was similar for the BU/CY/TBI
      group and the CY/TBI group (23% v 30%, P = .6), but there were trends toward
      lower relapse rates (28% v 54%, P = .27) and higher nonrelapse mortality rates
      (68% v 36%, P = .12) among the current patients compared with historical
      controls. Multivariate analysis showed that a normal karyotype pretransplant and
      the use of methotrexate as part of posttransplant immunosuppression were
      associated with improved survival and reduced nonrelapse mortality. Univariate
      analysis showed significant differences in relapse rates based on marrow source
      (57% for HLA genotypically matched marrow v 18% for all others, P = .04) and on
      disease morphology (66% for RAEB-T v 38% for RAEB and CMML, P = .05). CONCLUSION:
      Patients with advanced morphology myelodysplasia tolerated the intensified
      BU/CY/TBI preparative regimen and reduced posttransplant immunosuppression
      poorly. Novel transplant procedures are needed to reduce relapse rates without
      increasing nonrelapse mortality rates. In addition, transplantation before
      progression to RAEB-T, if possible, may reduce the risk of relapse.

PMID- 8558202
TI  - CEOP-IMVP-Dexa in the treatment of aggressive lymphomas: an Austrian multicenter
      trial.
AB  - PURPOSE: This trial evaluated the efficacy, toxicity, and practicability of a new
      intensive chemotherapy regimen in a multicenter setting of university and
      community hospitals. PATIENTS AND METHODS: We tested a hybrid protocol of two non
      cross-resistant regimens, cyclophosphamide, epirubicin, vincristine, and
      prednisolone (CEOP) and ifosfamide, etoposide (VP-16), methotrexate, and
      dexamethasone (IMVP-Dexa) given every fourth week, three to six times according
      to response, in patients with untreated intermediate- and high-grade non
      Hodgkin's lymphoma. Ten Austrian centers entered 81 patients onto this
      multicenter trial. Eleven patients were excluded. The median age was 55 years.
      Twenty-six of 70 patients had stage III or IV disease. The distribution among
      international risk categories low, intermediate-low, intermediate-high, and high
      was 20%, 34%, 23%, and 23%, respectively. RESULTS: Of 70 eligible patients, 56
      (80%) had a complete remission and seven (10%) a partial remission. After a
      median observation time of 36 months, the estimated time to relapse and overall
      survival rates are 67% and 72%, respectively. Age and Karnofsky index were the
      only independent risk factors for survival. Toxicity was primarily hematologic,
      with a median granulocyte nadir of 0.56 x 10(9)/L. Sixty-seven percent of
      patients had infections; 25.7% were severe World Health Organization (WHO) grade
      III or IV. There were three treatment-related deaths. CONCLUSION: CEOP-IMVP-Dexa
      chemotherapy is safe and feasible on a groupwide basis even when used in
      community hospitals. Neutropenic infections are the major complications. A 72% 3
      year survival rate in patients with intermediate- and high-grade non-Hodgkin's
      lymphoma warrants further studies. These data are the basis for a randomized
      trial to compare cyclophosphamide, doxorubicin, vincristine, and prednisolone
      (CHOP) with CEOP/IMVP-Dexa.

PMID- 8558203
TI  - Cyclosporin A does not reverse clinical resistance to paclitaxel in patients with
      relapsed non-Hodgkin's lymphoma.
AB  - PURPOSE: Cyclosporin A has been shown to reverse paclitaxel resistance in vitro
      by inhibiting P-gp function. Therefore, we determined whether addition of
      cyclosporine to paclitaxel reversed clinical paclitaxel resistance in patients
      with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients with relapsed
      NHL were eligible if they had no intervening treatment after failure to respond
      to paclitaxel (200 mg/m2 over 3 hours), and if they had adequate marrow, renal,
      and hepatic function, no serious cardiac disease, no CNS involvement, and no
      antibodies to human immunodeficiency virus-1. A cyclosporin A bolus dose (5 mg/kg
      over 3 hours) was followed by intravenous infusion (15 mg/kg) over 24 hours. Six
      hours after the beginning of cyclosporin A, the immediately preceding paclitaxel
      dose was administered over 3 hours. All patients were premedicated with
      dexamethasone, diphenhydramine, and cimetidine. Response was assessed after two
      cycles, and those patients who achieved at least a partial response received a
      maximum of six courses. RESULTS: All 26 patients entered were assessable for
      toxicity and 25 were assessable for response. One patient whose disease had
      progressed during paclitaxel treatment had a partial remission after the addition
      of cyclosporin A (response rate, 4%; 95% confidence interval, 1% to 20%). Disease
      progressed in 17 patients (71%) and did not respond in seven (25%). Serum
      cyclosporin A A levels measured at the time of initiation of paclitaxel infusion
      were greater than 2,000 ng/mL during 81% of cycles. Treatment toxicity included
      peripheral neuropathy in 57%, myalgia or arthralgia in 30%, neutropenia in 53%,
      neutropenic fever in 8%, and thrombocytopenia in 42% of patients. One patient
      with preexisting asthma had an acute bronchospasm during the first cycle and was
      removed from the study. There were no renal or hepatic toxicity and no infectious
      or hemorrhagic deaths. CONCLUSION: Cyclosporin A administered on this schedule
      did not reverse established clinical resistance to paclitaxel, which suggests
      that P-gp-mediated drug efflux is unlikely to be the only cause of paclitaxel
      resistance in this patient population.

PMID- 8558204
TI  - Is the small non-cleaved-cell lymphoma histologic subtype a poor prognostic
      factor in adult patients? A case-controlled analysis. The Groupe d'Etude des
      Lymphomes de l'Adulte.
AB  - PURPOSE: To study the prognostic significance of the small non-cleaved-cell
      lymphoma (SNCCL) histologic subtype, we compared the outcome of adult patients
      with SNCCL with that of patients with aggressive lymphoma other than SNCCL by
      means of two case-controlled studies. PATIENTS AND METHODS: We analyzed the
      results of the doxorubicin, cyclophosphamide, vindesine, bleomycin, and
      prednisone (ACVBP) regimen used as a reference scheme in our cooperative study
      group (Groupe d'Etude des Lymphomes de l'Adult [GELA]) in 52 adult SNCCL patients
      with no bone marrow (BM) or CNS involvement. Forty-five SNCCL patients younger
      than 60 years could be compared with two separate case-matched groups of patients
      with aggressive lymphoma other than SNCCL undergoing the same therapeutic
      regimen. In the first case-controlled study, matching ensured identity of each
      risk factor of the age-adjusted International Index (ie, Ann Arbor stage,
      performance status, and lactate dehydrogenase [LDH] level); in the second study,
      matching was performed according to the number of presenting risk factors (zero,
      one, two, or three), regardless of their nature. RESULTS: The 5-year overall
      survival rates were not significantly different between SNCCL and control
      patients in both case-controlled studies: 48% versus 51% in the first study, and
      48% versus 55% in the second study. CONCLUSION: These results support the thesis
      that in patients with no bone marrow or CNS involvement, the SNCCL histologic
      subtype does not confer a prognosis worse than that of other aggressive lymphoma.

PMID- 8558205
TI  - Phase I trial of buthionine sulfoximine in combination with melphalan in patients
      with cancer.
AB  - PURPOSE AND METHODS: Resistance to alkylating agents and platinum compounds is
      associated with elevated levels of glutathione (GSH). Depletion of GSH by
      buthionine sulfoximine (BSO) restores the sensitivity of resistant tumors to
      melphalan in vitro and in vivo. In a phase I trial, each patient received two
      cycles as follows: BSO alone intravenously (i.v.) every 12 hours for six doses,
      and 1 week later the same BSO as cycle one with melphalan (L-PAM) 15 mg/m2 i.v. 1
      hour after the fifth dose. BSO doses were escalated from 1.5 to 17 g/m2 in 41
      patients. RESULTS: The only toxicity attributable to BSO was grade I or II
      nausea/vomiting in 50% of patients. Dose-related neutropenia required an L-PAM
      dose reduction to 10 mg/m2 at BSO 7.5 g/m2. We measured GSH in peripheral
      mononuclear cells (PMN), and in tumor biopsies when available, at intervals
      following BSO dosing. In PMNs, GSH content decreased over 36 to 72 hours to reach
      a nadir on day 3; at the highest dose, recovery was delayed beyond day 7. The
      mean PMN GSH nadirs were approximately 10% of control at BSO doses > or = 7.5
      g/m2; at 13 and 17 g/m2, all but two patients had nadir values in this range. GSH
      was depleted in sequential tumor biopsies to a variable extent, but with a
      similar time course. At BSO doses > or = 13 g/m2, tumor GSH was < or = 20% of
      starting values on day 3 in five of seven patients; recovery had not occurred by
      day 5. We measured plasma concentrations of R- and S-BSO by high-performance
      liquid chromatography (HPLC) in 22 patients throughout the dosing period. Total
      body clearance (CLt) and volume of distribution at steady-state (Vss) for both
      isomers were dose-independent. The CLt of S-BSO was significantly less than that
      of R-BSO at all doses, but no significant differences in Vss were observed
      between the racemates. Harmonic mean half-lives were 1.39 hours and 1.89 hours
      for R-BSO and S-BSO, respectively. CONCLUSION: A biochemically appropriate dose
      of BSO for use on this schedule is 13 g/m2, which will be used in phase II trials
      to be conducted in ovarian cancer and melanoma.

PMID- 8558206
TI  - Clinical relevance of CD44 cell-surface expression and N-myc gene amplification
      in a multicentric analysis of 121 pediatric neuroblastomas.
AB  - PURPOSE: In contrast to other human tumors, a repression of the cell-surface
      glycoprotein CD44 on neuroblastoma is a marker of aggressiveness that usually
      correlates to N-myc amplification. We thus compared the prognostic value of both
      markers in the initial staging of 121 children treated for neuroblastoma in
      collaborative institutions. METHODS: Frozen samples were analyzed by a rapid and
      well-standardized technique of immunostaining with monoclonal antibodies (MoAbs)
      against epitopes in the CD44 constant region. RESULTS: In this retrospective
      series, CD44 was expressed on 102 specimens and strongly correlated with
      favorable tumor stages and histology, younger age, and normal N-myc copy numbers.
      In univariate analysis, CD44 expression and normal N-myc were the most powerful
      markers of favorable clinical outcome (P < 10(-6) and chi 2 = 65.40 and P < 10(
      6) and chi 2 = 42.56, respectively), but analysis of CD44 affords significant
      prognostic discrimination in subgroups of patients with or without N-myc
      amplified tumors. In the subgroup of stage IV neuroblastomas, CD44 was the only
      significant prognostic marker (P < .02, chi 2 = 5.76), whereas N-myc status was
      not discriminant. In multivariate analysis of five factors, ie, N-myc
      amplification, CD44 expression, age, tumor stage, and histology, the only
      independent prognostic factors of event-free survival were CD44 expression and
      tumor stage. CONCLUSION: The analysis of CD44 cell-surface expression must be
      recommended as an additional biologic marker in the initial staging of the
      disease.

PMID- 8558207
TI  - Predicting etoposide toxicity: relationship to organ function and protein
      binding.
AB  - PURPOSE: To investigate the effect of organ function on total and free etoposide
      pharmacokinetics and hematologic toxicity. PATIENTS AND METHODS: Seventy-two
      patients who received single-agent intravenous (i.v.) etoposide over 5 or 8 days
      (total dose, 500 mg/m2) were studied. Pharmacokinetic parameters were derived
      after analysis of total plasma etoposide by high-performance liquid
      chromatography (HPLC) with ultraviolet (UV) detection, and etoposide protein
      binding by ultrafiltration of an etoposide-spiked, pretreatment serum sample,
      followed by HPLC analysis. Free etoposide area under the concentration-time curve
      (AUC) was derived from the total AUC and protein binding. RESULTS: Patients with
      renal impairment (serum creatinine level > 130 mumol/L) had a lower plasma
      etoposide clearance (13.6 v 18.5 mL/min/m2; P = .016), resulting in an increased
      total-drug and free-drug AUC (total etoposide AUC 615 v 452 micrograms/mL.hr; P =
      .016; free etoposide AUC 26.0 v 17.6 micrograms/mL.hr; P = .026) and increased
      hematologic toxicity (nadir neutrophil count 0.3 v 1.9 x 10(9)/L; P = .005).
      Patients with albumin levels less than 35 g/L had no change in total etoposide
      kinetics but had an increase in unbound etoposide (5.2% v 4.1%; P = .01),
      resulting in an increase in free etoposide AUC (27.5 v 16.5 micrograms/mL.hr; P =
      .003) and more profound toxicity (nadir neutrophil count 0.6 v 1.9 x 10(9)/L; P =
      .004). In patients with normal albumin and creatinine, increased toxicity in
      those older than 65 years was associated with a reduced drug clearance, and in
      those with increased liver enzymes by a trend toward an increase in free
      etoposide AUC. CONCLUSION: Increased hematologic toxicity after etoposide in
      patients with abnormal organ function is mediated by an increase in free
      etoposide AUC. A reduction in dose is clearly indicated in such patients.

PMID- 8558208
TI  - Randomized phase II trial comparing different doses of the bisphosphonate
      ibandronate in the treatment of hypercalcemia of malignancy.
AB  - PURPOSE: To evaluate the hypocalcemic effect and safety of three different doses
      of the bisphosphonate ibandronate in tumor-associated hypercalcemia, and to
      identify factors predicting response. PATIENTS AND METHODS: One hundred seventy
      four cancer patients with a serum calcium level greater than 2.7 mmol/L (10.8
      mg/dL) were enrolled onto the trial. If hypercalcemia persisted after fluid
      repletion, patients were randomly assigned to treatment with 0.6 mg, 1.1 mg, and
      2.0 mg of ibandronate. Response, defined as restoration of normocalcemia, was
      evaluated by an intent-to-treat analysis. RESULTS: One hundred seventy-three
      (99%) patients were assessable for toxicity and 151 (87%) for efficacy. The
      administration of 0.6 mg (group A), 1.1 mg (group B), or 2.0 mg (group C) of
      ibandronate led to response rates of 44%, 52%, and 67%, respectively.
      Significantly more patients in group C responded than in group A (P = .0276). Of
      the various parameters examined, only the initial serum calcium level (P < .0001;
      odds ratio, 0.083) and the dose of ibandronate (P = .0162; odds ratio, 2.094)
      correlated with response. One hundred ninety-five adverse events (AEs) were
      reported, 99 classified as serious and 96 as nonserious. Three serious and
      sixteen nonserious AEs were considered related to ibandronate treatment. The
      three serious AEs were one case with thrombocytopenia, one with nausea, and one
      with fever. CONCLUSION: Ibandronate therapy led to a dose-dependent reduction in
      serum calcium levels. The response to ibandronate treatment correlated negatively
      with the initial serum calcium level and positively with the dose administered. A
      dose of 2 mg was necessary to achieve a response rate comparable to that in
      previous studies with the bisphosphonates pamidronate and clodronate. Because the
      incidence of drug-associated AEs was low, a dose escalation of ibandronate can be
      recommended for further clinical trials.

PMID- 8558209
TI  - Phase I/II study of combined granulocyte colony-stimulating factor and
      granulocyte-macrophage colony-stimulating factor administration for the
      mobilization of hematopoietic progenitor cells.
AB  - PURPOSE: To study the toxicity and efficacy of combined granulocyte colony
      stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor
      (GM-CSF) administration for mobilization of hematopoietic progenitor cells
      (HPCs). MATERIALS AND METHODS: Cohorts of a minimum of five patients each were
      treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM
      CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5
      micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort
      4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten
      liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13.
      Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and
      erythroid burst-forming units (BFU-E) were performed on each harvest. RESULTS:
      The principal toxicities were myalgias, bone pain, fever, nausea, and mild
      thrombocytopenia, but none was dose-limiting. Four days of treatment with either
      G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of
      CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7
      +/- 13.0-fold increases over baseline, respectively. This increment was
      attributable both to increased numbers of mononuclear cells collected per 10-L
      apheresis and to increased concentrations of progenitors within each collection.
      The administration of G-CSF to patients already receiving GM-CSF (cohort 4)
      caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the
      reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The
      CFU-GM content of the baseline aphereses correlated with the maximal mobilization
      achieved (r = .74, P = .001). CONCLUSION: Combined G-CSF and GM-CSF
      administration effectively and predictably mobilizes HPCs and facilitates
      apheresis.

PMID- 8558210
TI  - Design and results of phase I cancer clinical trials: three-year experience at
      M.D. Anderson Cancer Center.
AB  - PURPOSE: Alternatives to the standard design for conducting phase I trials are
      proposed with increasing frequency. This study was undertaken to determine how
      phase I trials are currently conducted and to provide a basis for evaluation of
      evolving methodology. SUBJECTS AND METHODS: All published phase I trials from a
      single institution over a 3-year period were reviewed to determine the method of
      selection of the recommended dose for a phase II trial of a new agent, type and
      extent of toxicity, number of patients treated at the recommended dose, and
      clinical response. RESULTS: All 23 published trials used the standard method of
      entering cohorts of patients at increasing dose levels and observing toxic
      effects to determine the dose recommended for phase II study. Among 610 patients,
      26% were treated at or within 10% of the recommended dose and 35% were treated
      with less than 50% of the recommended dose or on a trial that yielded no
      recommended dose. Among 18 trials using agents previously tested in humans, fewer
      patients were treated at much less than the recommended dose. For trials in which
      myelosuppression was dose-limiting, the estimated probability of serious
      myelosuppression associated with the recommended dose ranged from 23% to 66%.
      Nineteen patients (3%) responded to therapy. CONCLUSION: This summary of phase I
      trials recently conducted at M.D. Anderson Cancer Center confirms the need for
      alternative methods, provides baseline information against which alternatively
      conducted trials can be compared, and demonstrates some practical clinical trial
      issues not generally considered when alternative methods are proposed.

PMID- 8558211
TI  - New statistical strategy for monitoring safety and efficacy in single-arm
      clinical trials.
AB  - PURPOSE: Efficacy and toxicity are both important outcomes in cancer clinical
      trials. Nonetheless, most statistical designs for phase II trials only provide
      rules for evaluating treatment efficacy, and moreover only allow early stopping
      after fixed cohorts of patients have been treated. We illustrate a new
      statistical design strategy for monitoring both adverse and efficacy outcomes on
      a patient-by-patient basis in phase II and other single-arm clinical trials.
      DESIGN: The new strategy is used to design a phase II trial of the experimental
      regimen idarubicin plus cytarabine (ara-C) plus cyclosporine for treatment of
      patients with intermediate-prognosis acute myelogenous leukemia (AML). The design
      requires a maximum of 56 patients and provides continuous monitoring boundaries
      to terminate the trial if the toxicity rate is unacceptably high or the complete
      remission (CR) rate is unacceptably low compared with the rates of these events
      with the standard regimen of anthracycline plus ara-C. RESULTS: The design has an
      88% to 91% probability of stopping the trial early with a median of 15 to 18
      patients if the toxicity rate of the experimental regimen is .05 to .10 above
      that of the standard and there is no improvement in the CR rate. If there is a
      .15 improvement in the CR rate and the toxicity rate is no more than .05 above
      that of the standard, then there is at least an 83% probability that the trial
      will run to completion. CONCLUSION: The proposed monitoring strategy provides a
      flexible, practical means to continuously monitor both safety and efficacy in
      single-arm cancer clinical trials. The design strategy can be implemented easily
      using a freely available menu-driven computer program, and provides a
      scientifically sound alternative to the use of ad hoc safety monitoring rules.

PMID- 8558212
TI  - Role of interstitial radiotherapy in the management of clinically organ-confined
      prostate cancer: the jury is still out.
AB  - PURPOSE AND DESIGN: To discuss the evolution of the use of brachytherapy in the
      treatment of clinically organ-confined prostate cancer and to review modern
      techniques, results of therapy, and optimal patient selection criteria. RESULTS:
      Using modern localization and immobilization techniques, interstitial prostate
      radiotherapy for patients with a prostate-specific antigen (PSA) level less than
      10 ng/mL yields an at least 87% rate of freedom from biochemical relapse at 3
      years, which is numerically equivalent to results achieved with external-beam
      radiotherapy or radical prostatectomy. With a minimum median follow-up time of 24
      months, 81% to 85% (2-year actuarial and 3-year crude) potency rates have been
      reported concomitant with 2-year actuarial rates of 12% for grade > or = 2 rectal
      complications and 10% for grade > or = 3 urethral complications. CONCLUSION: The
      combination of clinical stage, PSA level, and biopsy Gleason sum allows for
      selection of patients with the highest probability of having all of the prostate
      cancer encompassed by the high-dose implant volume, while simultaneously
      respecting the normal-tissue tolerance doses of the juxtaposed normal tissues
      (rectum and bladder). In particular, patients with nonpalpable (T1c) lesions, a
      biopsy Gleason sum < or = 6 (ideally < or = 4), and a PSA level less than 10
      ng/mL represent the optimal implant candidates. Differential loading of the
      implant away from the geometric center and not accepting patients with large
      prostate glands (> or = 60 cm3) or history of a transurethral resection of the
      prostate (TURP) as implant candidates, may reduce urethral toxicity. Further
      follow-up evaluation of prostate cancer patients treated with interstitial
      radiotherapy will verify if favorable potency preservation rates and rates of
      freedom from biochemical failure equivalent to those achieved with radical
      prostatectomy or external-beam radiation therapy are maintained.

PMID- 8558213
TI  - Physician-drug company conflict of interest.

PMID- 8558214
TI  - Changing the behavior of breast cancer.

PMID- 8558215
TI  - Schedule-dependent edatrexate toxicity.

PMID- 8558216
TI  - Treatment of rhabdomyosarcoma.

PMID- 8558218
TI  - Selecting treatment for children with acute lymphoblastic leukemia.

PMID- 8558217
TI  - Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil,
      epirubicin, and cyclophosphamide chemotherapy in premenopausal women with
      axillary node-positive operable breast cancer: results of a randomized trial. The
      International Collaborative Cancer Group.
AB  - PURPOSE: To determine whether a combination chemotherapy regimen that contains
      epirubicin (fluorouracil, epirubicin, and cyclophosphamide [FEC]) is superior to
      the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination
      in premenopausal women with axillary node-positive operable breast cancer.
      PATIENTS AND METHODS: The International Collaborative Cancer Group (ICCG)
      conducted a large randomized trial in which two alternative schedules were used
      according to participating center: CMF1 versus FEC1 and CMF2 versus FEC2.
      RESULTS: Seven hundred fifty-nine patients were entered onto the trial. At a
      median follow-up time of 4.5 years, no significant benefit for the anthracycline
      containing regimen was observed in terms of relapse-free (P = .61) or overall
      survival (P = .13). FEC1 and CMF1 appear to be of similar efficacy, but there is
      a suggestion that FEC2 may be superior to CMF2, since patients who received FEC2
      had improved overall (P = .02) and relapse-free survival (P = .03) rates. Nausea
      and vomiting and alopecia were more common in the epirubicin-containing regimen
      (P = .001). CONCLUSION: We conclude that the FEC2 regimen, in which epirubicin
      replaced the methotrexate in CMF, is the preferable adjuvant chemotherapy regimen
      for premenopausal patients with operable axillary node-positive breast cancer.

PMID- 8558219
TI  - Adjuvant CMFVP versus adjuvant CMFVP plus ovariectomy for premenopausal, node
      positive, and estrogen receptor-positive breast cancer patients: a Southwest
      Oncology Group study.
AB  - PURPOSE: To determine whether the addition of surgical ovariectomy to standard
      chemotherapy prolongs disease-free survival (DFS) and overall survival in
      premenopausal patients with estrogen receptor (ER)-positive operable breast
      cancer with positive axillary nodes. PATIENTS AND METHODS: Three hundred fourteen
      premenopausal patients with ER-positive, node-positive breast cancer were
      enrolled between July 1979 and July 1989. Patients were stratified according to
      number of involved nodes and type of primary surgery and randomized to receive
      either of the following: (1) cyclophosphamide 60 mg/m2/d by mouth for 1 year,
      methotrexate 15 mg/m2 intravenously (i.v.) weekly for 1 year, fluorouracil (5-FU)
      400 mg/m2 i.v. weekly for 1 year, vincristine .625 mg/m2 i.v. weekly for the
      first 10 weeks, and prednisone weeks 1 to 10 with doses decreasing from 30 mg/m2
      to 2.5 mg/m2 (CMFVP); or (2) bilateral ovariectomy followed by CMFVP. RESULTS:
      The median follow-up time is 7.7 years and the maximum 13.2 years. Treatment arms
      are not significantly different with respect to either survival or DFS (one-sided
      log-rank, P = .55 and .70, respectively). The 7-year survival rate is 71% on the
      CMFVP arm and 73% on CMFVP plus ovariectomy. No significant differences were
      observed in node or receptor level subsets. CONCLUSION: We conclude that, in this
      study, the addition of ovariectomy did not improve results over chemotherapy
      alone in the treatment of premenopausal women with node-positive, ER-positive,
      operable breast cancer. Our sample size was too small to detect a small
      improvement. The death hazards ratio of CMFVP/CMFVP plus ovariectomy was 1.22
      (95% confidence interval [CI], .79 to 1.89).

PMID- 8558220
TI  - Ipsilateral breast tumor recurrence as a predictor of distant disease:
      implications for systemic therapy at the time of local relapse.
AB  - PURPOSE: To evaluate the prognostic significance of ipsilateral breast tumor
      recurrence (IBTR) with respect to the subsequent development of distant
      metastasis. MATERIALS AND METHODS: Between January 1970 and December 1989, 973
      patients with invasive breast cancer were treated with conservative surgery and
      radiation therapy at Yale-New Haven Hospital. The median follow-up time as of
      December 1993 was 8.6 years. A number of prognostic factors were tested as
      possible predictors of distant metastases, including whether a patient
      experienced IBTR. IBTRs were broken down by time to recurrence to determine
      whether the breast recurrence-free interval had any prognostic relevance with
      respect to the development of distant metastasis. RESULTS: As of December 1993,
      out of the entire population of 973 patients, 73 patients had developed IBTR and
      134 had developed distant metastases. The overall actuarial survival rate at 10
      years was .71 +/- .02, with a 10-year actuarial breast recurrence-free rate of
      .84 +/- .02 and a 10-year distant metastasis-free rate of .77 +/- .02. The
      overall distant metastasis rate was higher in patients who experienced IBTR
      compared with patients who had never experienced IBTR. Furthermore, the time to
      IBTR had a significant effect on distant metastases. Of 32 patients who developed
      an IBTR within 4 years of original diagnosis, 16 (50%) developed distant
      metastases. In contrast, of 41 patients who developed later breast relapses (> 4
      years from original diagnosis), only seven (17%) developed distant metastases (P
      < .01). Of 32 patients who developed early breast relapse, the 5-year survival
      rate following breast relapse was .50 +/- .01, compared with a 5-year post-breast
      relapse survival rate of .78 +/- .10 among 41 patients with later breast relapses
      (P < .05). CONCLUSION: It appears that early IBTR is a significant predictor for
      distant metastases. Whether early breast tumor relapse is a marker for or cause
      of distant metastases remains a controversial and unresolved issue. Implications
      for adjuvant systemic therapy at the time of breast relapse are discussed.

PMID- 8558221
TI  - Phase II and pharmacologic study of docetaxel as initial chemotherapy for
      metastatic breast cancer.
AB  - PURPOSE: Because docetaxel (Taxotere, RP 56976; Rhone-Poulenc Rorer, Antony,
      France) appeared to be active against breast cancer in phase I trials, we
      performed this phase II study. PATIENTS AND METHODS: Thirty-seven patients with
      measurable disease were enrolled. Only prior hormone therapy was allowed, as was
      adjuvant chemotherapy completed > or = 12 months earlier. Docetaxel 100 mg/m2 was
      administered over 1 hour every 21 days. Diphenhydramine hydrochloride and/or
      corticosteroid premedication was added after hypersensitivity-like reactions
      (HSRs) were seen in two of the first six patients. Pharmacokinetic studies were
      performed during cycle 1 for correlation with toxicity. RESULTS: Thirty-seven
      patients were assessable. Nineteen (51%) required dose reductions, usually for
      neutropenic fever. The median nadir WBC count was 1.4 x 10(3)/microL. HSRs were
      noted in 20 patients (54%). At a median cumulative dose of 297 mg/m2 (range, 99.6
      to 424.5 mg/m2), 30 patients (81%) developed fluid retention, for which 11 (30%)
      subsequently stopped treatment. The first-cycle plasma area under the
      concentration-time curve (AUC) did not correlate with toxicity, although an
      ineligible patient with hepatic metastases (pretreatment bilirubin level 1.8
      mg/dL) had an elevated AUC and died of toxicity. Responses were seen at all
      sites. On an intent-to-treat basis, there were two (5%) complete responses (CRs)
      and 18 (49%) partial responses (PRs). The overall response proportion (CRs plus
      PRs) was 54% (95% confidence interval, 37% to 71%). The median time to response
      was 12 weeks (range, 3 to 15) and the median duration was 26 weeks (range, 10 to
      58+). CONCLUSION: Docetaxel is active for metastatic breast cancer. Neutropenia
      and fluid retention are dose-limiting. The AUC did not predict toxicity, but
      caution is warranted when treating patients with liver dysfunction. An
      understanding of the pathophysiology of the fluid retention may facilitate
      prevention. Frequent HSR may warrant prophylactic premedication.

PMID- 8558222
TI  - Outcome of extensive evaluation before adjuvant therapy in women with breast
      cancer and 10 or more positive axillary lymph nodes.
AB  - PURPOSE: To evaluate the effect of extensive screening of women with high-risk,
      node-positive breast cancer on the detection of occult metastatic disease and
      patient eligibility for a randomized trial of the addition of high-dose
      chemotherapy and autologous bone marrow support (ABMT) to standard adjuvant
      therapy. PATIENTS AND METHODS: Women with resected T1-3N1,2 primary breast cancer
      and > or = 10 positive axillary lymph nodes referred for possible trial
      participation were evaluated for this report. All had normal chest x-ray, bone
      scan, and liver ultrasound performed by the referring physician. Those who
      provided informed consent for the randomized trial were further evaluated
      according to protocol with computed tomographic (CT) scans of the head, chest,
      abdomen, and pelvis and bilateral bone marrow biopsies; those with metastatic
      disease detected by any of these tests were excluded from study registration.
      RESULTS: Forty-four women were evaluated between February 1993 and April 1995.
      Fourteen did not undergo further protocol staging because of refusal to
      participate or the presence of metastatic disease on clinical assessment or
      review of outside radiologic studies. The remaining 30 underwent additional
      investigations, and seven (23%; 95% confidence interval [CI], 12% to 41%) had
      metastases detected by CT scanning (four patients) or bone marrow biopsy (three
      patients) not detected by routine screening. CONCLUSION: Although the number of
      patients evaluated is small, these data suggest that some of the improvement in
      outcome of women with > or = 10 positive axillary lymph nodes who receive ABMT as
      part of adjuvant chemotherapy in phase II trials may be from the exclusion of
      patients with occult metastatic disease. The importance of these exclusions can
      only be determined by ongoing, randomized controlled trials.

PMID- 8558223
TI  - Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the
      Eastern Cooperative Oncology Group Trial EST 1684.
AB  - PURPOSE: Interferon alfa-2b (IFN alpha-2b) exhibits antitumor activity in
      metastatic melanoma and on this basis has been evaluated as an adjuvant therapy
      following surgery for deep primary (T4) or regionally metastatic (N1) melanoma.
      METHODS: A randomized controlled study of IFN alpha-2b (Schering-Plough,
      Kenilworth, NJ) administered at maximum-tolerated doses of 20 MU/m2/d
      intravenously (i.v.) for 1 month and 10 MU/m2 three times per week subcutaneously
      (SC) for 48 weeks versus observation, was conducted by the Eastern Cooperative
      Oncology Group (ECOG) in 287 patients. RESULTS: A significant prolongation of
      relapse-free survival (P = .0023, one-sided) and prolongation of overall survival
      (P = .0237, one-sided) was observed with IFN alpha-2b therapy in this trial,
      which is now mature with a median follow-up time of 6.9 years. The impact of
      treatment on relapse rate is most pronounced early during the treatment interval.
      The overall benefit of treatment in this trial was analyzed stratified by tumor
      burden and the presence or absence of microscopic nonpalpable and palpable
      regional lymph node metastasis. The benefit of therapy with IFN alpha-2b was
      greatest among node-positive strata. Toxicity of IFN alpha-2b required dose
      modification in the majority of patients, but treatment at > or = 80% of the
      scheduled dose was feasible in the majority of patients through the IV phase of
      treatment, and for more than 3 months of SC maintenance therapy. Discontinuation
      of treatment due to toxicity was infrequent after the fourth month of therapy.
      CONCLUSION: IFN alpha-2b prolongs the relapse-free interval and overall survival
      of high-risk resected melanoma patients. The increment in median disease-free
      survival (from 1 to 1.7 years) and overall survival (from 2.8 to 3.8 years) that
      results from this therapy is associated with a 42% improvement in the fraction of
      patients who are continuously disease-free after treatment with IFN (from 26% to
      37%) in comparison to observation. IFN alpha-2b is the first agent to show a
      significant benefit in relapse-free and overall survival of high-risk melanoma
      patients in a randomized controlled trial.

PMID- 8558224
TI  - Trade-offs between survival and breast preservation for three initial treatments
      of ductal carcinoma-in-situ of the breast.
AB  - PURPOSE: To assess the trade-offs between survival and breast preservation of
      currently accepted approaches for ductal carcinoma-in-situ (DCIS) of the breast.
      PATIENTS AND METHODS: Decision analysis was performed using the Markov model of
      hypothetical cohorts of 55-year-old white women with nonpalpable mammographic
      abnormalities found to be DCIS. Strategies were breast-conserving surgery (BCS),
      BCS with 50-Gy radiation (RT) or initial mastectomy. Recurrence rates were
      derived from the published literature. Main outcomes were overall, breast cancer
      free, and event-free survival plus years of both breasts preserved. RESULTS:
      Using the conditions defined in this model, the actuarial survival rates at 10
      and 20 years were 91.7% and 74.1% for the initial mastectomy strategy, 91.0% and
      72.1% for BCS plus RT, and 89.6% and 68.2% for BCS alone. At 20 years, the
      initial mastectomy strategy also had a greater breast cancer-free survival rate
      of 74.5%, compared with 63.3% for BCS plus RT, or 46.8% for BCS alone. However,
      BCS alone had the highest survival rate with both breasts preserved (64.2%)
      compared with BCS plus RT (56.0%) or initial mastectomy (0%). Of the breast
      conserving strategies at 20 years, the breast event-free survival rate (no
      invasive cancer or DCIS) was greater for BCS plus RT (47.2%) compared with BCS
      alone (28.4%). Using just survival as the primary end point, mastectomy is the
      optimal strategy by a small margin. However, if quality-adjusted survival is at
      issue, mastectomy is the choice only if the yearly reduction in quality of life
      due to mastectomy is less than 1%. CONCLUSION: BCS with or without radiation
      compared with mastectomy as initial management of DCIS of the breast trades a
      slight decrease in survival rates for the value of breast preservation. This
      model should aid clinicians in matching treatments to their patients'
      preferences.

PMID- 8558225
TI  - Effect of tamoxifen on bone mineral density measured by dual-energy x-ray
      absorptiometry in healthy premenopausal and postmenopausal women.
AB  - PURPOSE: Tamoxifen is an effective treatment for metastatic and primary breast
      cancer and is now being evaluated as a chemoprevention agent in healthy women.
      Any long-term effects on estrogen-sensitive tissues such as bone may have
      important therapeutic implications. METHODS: We measured bone mineral density
      (BMD) in the lumbar spine and hip using dual-energy x-ray absorptiometry (DXA) in
      premenopausal and postmenopausal healthy women who participated in our placebo
      controlled tamoxifen chemoprevention of breast cancer trial. RESULTS: BMD data
      are now available from 179 women for this analysis. In premenopausal women, BMD
      decreased progressively in the lumbar spine (P < .001) and in the hip (P < .05)
      for women on tamoxifen, but not those on placebo. The mean annual loss in lumbar
      BMD per year over the 3-year study period in tamoxifen-treated compliant women
      who remained premenopausal throughout the study period was 1.44% (1.88%
      calculated on an intent-to-treat basis) compared with a small gain of 0.24% per
      annum for women on placebo (P < .001). Tamoxifen had the opposite effect in
      postmenopausal women. The mean annual increase in BMD for women on tamoxifen was
      1.17% in the spine (P < .005) and 1.71% in the hip (P < .001) compared with a
      noninsignificant loss for women on placebo. CONCLUSION: These results indicate
      that tamoxifen treatment is associated with a significant loss of BMD in
      premenopausal women, whereas it prevents bone loss in postmenopausal women. These
      adverse and beneficial effects of tamoxifen should be considered in the
      assessment of the therapeutic benefits for both the adjuvant treatment and the
      chemoprevention of breast cancer.

PMID- 8558226
TI  - Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas.
AB  - PURPOSE: Experiments were designed to investigate the association between tumor
      leukocytic infiltrates with other pathologic and biologic variables in primary
      tumors and with prognosis, and to define the phenotype of the infiltrating
      leukocytes. PATIENTS AND METHODS: A retrospective series of 1,207 primary breast
      carcinomas was studied according to different prognostic variables, including the
      presence of lymphoplasmacytic infiltrate (LPI). LPI was analyzed in association
      with other variables and survival. Additionally, a small prospective series of
      surgical specimens from 75 primary breast carcinomas with infiltrating leukocytes
      was tested by immunohistochemistry on frozen sections to phenotypically
      characterize the infiltrate, using anti-CD reagents, and the tumor, using anti-c
      erbB-2 oncoprotein monoclonal antibody. RESULTS: In the retrospective series,
      menopausal status, nodal status, tumor size, stage, grade, and p185HER2
      overexpression but not LPI were found to be associated with prognosis and
      maintained their prognostic significance in a multivariate analysis. LPI was
      significantly associated with some of these independent prognostic factors, such
      as tumor size (P = .03), stage (P = .004), grade III carcinomas (P < .000001),
      and overexpression of the p185HER2 (P < .000001). In some subgroups of patients
      in whom LPI was found more frequently, such as grade III cases or N- and c-erbB-2
      positive cases, LPI was found to be indicative of a good prognosis (P = .008 and
      P = .03, respectively). Phenotypic analysis of the infiltrating leukocytes
      revealed a preponderance of macrophages in high-grade (P = .05) or c-erbB-2
      positive (P = .008) tumors, whereas T cells constituted most of the infiltrate in
      the other tumors. CONCLUSION: Our data demonstrate different leukocytic types in
      the infiltrate of breast tumors with different prognostic significance.

PMID- 8558227
TI  - Phase I study of paclitaxel in combination with cyclophosphamide and granulocyte
      colony-stimulating factor in metastatic breast cancer patients.
AB  - PURPOSE: In vitro data suggest that prolonged exposure to paclitaxel enhances
      breast cancer cytotoxicity. Our objective in this phase I study was to determine
      the tolerability of paclitaxel administered by 72-hour continuous intravenous
      (i.v.) infusion (CIVI) in combination with high-dose cyclophosphamide and
      granulocyte colony-stimulating factor (G-CSF) in the ambulatory setting to
      metastatic breast cancer patients. PATIENTS AND METHODS: Paclitaxel was
      administered over 72 hours by CIVI and cyclophosphamide was given daily by i.v.
      bolus on days 1, 2, and 3, followed by G-CSF every 21 days. The availability of
      ambulatory infusion pumps and paclitaxel-compatible tubing permitted outpatient
      administration. RESULTS: Fifty-five patients with metastatic breast cancer who
      had been previously treated with a median of two prior chemotherapy regimens were
      entered onto the study. Dose-limiting toxicity of grade 4 neutropenia for longer
      than 5 days and grade 4 thrombocytopenia occurred in three of five patients
      treated with paclitaxel 160 mg/m2 CIVI and cyclophosphamide 3,300 mg/m2 followed
      by G-CSF. The maximum-tolerated dose (MTD) was paclitaxel 160 mg/m2 CIVI and
      cyclophosphamide 2,700 mg/m2 in divided doses with G-CSF. Nonhematologic
      toxicities were moderate and included diarrhea, mucositis, and arthalgias.
      Although hemorrhagic cystitis developed in six patients, recurrence was prevented
      with i.v. and oral mesna, which permitted continued outpatient delivery. One
      hundred seventy-four cycles were safely administered in the ambulatory setting
      using infusional pumps and tubing. Objective responses occurred in 23 (one
      complete and 22 partial) of 42 patients with bidimensionally measurable disease
      (55%; 95% confidence interval, 38% to 70%), with a response rate of 73% (11 of
      15) seen at the highest dose levels. CONCLUSION: Paclitaxel by 72-hour CIVI with
      daily cyclophosphamide followed by G-CSF can be administered safely in the
      ambulatory setting, has acceptable toxicity, and is an active regimen in the
      treatment of metastatic breast cancer.

PMID- 8558229
TI  - Inhibition of the Kv4 (Shal) family of transient K+ currents by arachidonic acid.
AB  - We have found that transient A-type currents expressed in Xenopus oocytes from
      members of the Kv4 family are suppressed by arachidonic acid. Currents from
      members of the Kv1, Kv2, and Kv3 families showed little or no inhibition by fatty
      acids in this expression system, although Shaker currents showed a modest
      increase in peak amplitude. The inhibition of Kv4 channels was not prevented by
      cyclo-oxygenase, lipoxygenase, or cytochrome P-450 inhibitors and was mimicked by
      5,8,11,14-eicosatetraynoic acid, an arachidonic acid analog that is not
      metabolized by these pathways. Other unsaturated cis fatty acids with more than
      two double bonds produced a similar effect. In inside-out macropatches, the
      current was reversibly reduced > 50% by 2 mM arachidonic acid, and the inhibition
      developed in < 40 sec. These results suggest that, at concentrations that are
      likely to be physiologically relevant, arachidonic acid interacts directly with
      the channel or with a closely associated component. Preliminary mutagenesis of
      Kv4.2 channels indicates that the N terminal is not required for arachidonic acid
      action but that the S4-S5 loop may influence the effect.

PMID- 8558228
TI  - Modulation of calcium efflux from cultured rat dorsal root ganglion neurons.
AB  - The free intracellular Ca2+ concentration ([Ca2+]i) is governed by the balance
      between the activation of Ca2+ channels and buffering and efflux processes. We
      tested the hypothesis that Ca2+ efflux pathways are susceptible to modulation.
      The whole-cell patch-clamp technique was used in combination with Indo-1-based
      microfluorometry to record Ca2+ current and [Ca2+]i simultaneously from single
      rat dorsal root ganglion (DRG) neurons grown in culture. Depolarizing test pulses
      (-80 to 0 mV, 100-300 msec) elicited [Ca2+]i transients that recovered to basal
      levels by a process best-fit with a single exponential (tau = 5.1 +/- 0.4 sec; n
      = 14) and were independent of Ca2+ load (40-500 pC) over this range of test
      pulses. [Ca2+]i transients recorded in whole-cell configuration were similar to
      those elicited by a brief train of action potentials in unclamped neurons.
      Inhibition of Ca2+ sequestration into intracellular stores with thapsigargin had
      no effect on the kinetics of recovery. Inhibition of plasma membrane Ca2+ ATPase
      (PMCA) function by including a peptide inhibitor (C28R2) in the patch pipette
      significantly slowed recovery to basal [Ca2+]i (tau = 9.9 +/- 0.8 sec; n = 4).
      Preincubation with calmidazolium, a calmodulin antagonist, produced modest
      slowing of Ca2+ efflux. Phorbol dibutyrate, an activator of protein kinase C
      (PKC), accelerated Ca2+ efflux only when the PMCA had been inhibited by C28R2. We
      conclude that in DRG neurons PMCAs are responsible for lowering [Ca2+]i after
      small Ca2+ loads and that PMCA-mediated Ca2+ efflux is modulated by calmodulin-
      and PKC-signaling pathways.

PMID- 8558230
TI  - Isoproterenol potentiates synaptic transmission primarily by enhancing
      presynaptic calcium influx via P- and/or Q-type calcium channels in the rat
      amygdala.
AB  - The effects of selective beta-adrenergic receptor agonist isoproterenol (Iso) on
      neuronal excitability and synaptic transmission were investigated in brain slices
      of rat amygdala. Iso (15 microM) produced a long-lasting enhancement of the EPSP
      that was not blocked by pretreatment with 20 microM D-2-amino-5-phosphonovalerate
      (D-APV) alone or D-APV in combination with kynuretic acid (1 mM). The sensitivity
      of postsynaptic neurons to the glutamate receptor agonist AMPA was unchanged by
      Iso pretreatment. Superfusion of Iso reversibly blocked the after
      hyperpolarization (AHP) that followed a depolarizing current pulse and caused
      more action potential firing. Intracellular application of a selective inhibitor
      of the catalytic subunit of cAMP-dependent protein kinase A blocked the effect of
      Iso on the AHP, whereas Iso-induced potentiation was entirely normal in the same
      neuron. In addition, Iso decreased the magnitude of paired-pulse facilitation,
      which is consistent with a presynaptic mode of action. Substituting the Mg2+ for
      Ca2+ in the medium completely abolished the Iso-induced enhancement of the EPSP.
      The effect of Iso also was blocked by low concentrations of omega-agatoxin-IVA,
      but not by nifedipine or omega-conotoxin-GVIA. These results suggest that Iso
      enhances synaptic transmission in the amygdala via a presynaptic site of action:
      the mechanism underlying the potentiating effect likely is attributable to an
      increased Ca2+ influx through P- and/or Q-type Ca2+ channels.

PMID- 8558231
TI  - Beta-amyloid-related peptides inhibit potassium-evoked acetylcholine release from
      rat hippocampal slices.
AB  - The 4 kDa beta-amyloid (A beta) protein, a major component of cerebral and
      cerebrovascular plaques in Alzheimer's disease (AD), is derived from the
      proteolytic cleavage of a larger, membrane-bound precursor, the A beta precursor
      protein (APP). Until recently, it was assumed that an aberrant AD-specific
      proteolysis generated A beta peptides, which subsequently could initiate and/or
      contribute to the pathological cascade leading to plaque formation and losses of
      selected neuronal populations, including basal forebrain cholinergic neurons that
      provide major inputs to the hippocampus and neocortex. However, the recent
      detection of soluble A beta fragments in the plasma and CSF of normal
      individuals, as well as in the conditioned media of cultured brain cells,
      suggests a role for A beta-related peptides in normal brain functions. Taking
      into consideration the reported toxic properties of A beta and the preferential
      vulnerability of basal forebrain cholinergic neurons in AD, we investigated the
      possible effects of A beta-related peptides on the release of endogenous
      acetylcholine (ACh) from rat brain slices. A beta 1-28, in a concentration
      dependent manner (10(-12)-10(-8) M), potently inhibited K(+)-evoked ACh release
      from hippocampal slices. The inhibition of ACh release was fully reversible and
      was observed using other A beta-related peptides such as A beta 1-42, A beta 1
      40, and A beta 25-35, but not with the scrambled, reverse, or all D-isomer A beta
      peptide sequences, indicating that the effect of A beta on ACh release is
      mediated via a stereoselective mechanism. Tetrodotoxin (10 microM) failed to
      alter the effect of A beta 1-28 on ACh release, which suggests the lack of
      involvement of voltage-dependent Na+ channels. Except for the hippocampal
      formation, the inhibitory effect of A beta on K(+)-evoked ACh release also was
      observed in the frontal cortex but not in the striatum. Taken together, our
      results demonstrate that APP-derived A beta-related peptides can regulate the
      release of ACh potently by acting on cholinergic terminals. Additionally, the
      evidence that selected cholinergic neuronal populations are sensitive to A beta
      suggests a potential mechanistic link between the deposition of A beta and the
      preferential vulnerability of certain cholinergic projections in AD.

PMID- 8558232
TI  - Nimodipine accelerates axonal sprouting after surgical repair of rat facial
      nerve.
AB  - Facial-facial anastomosis (FFA), i.e., suture of transected facial nerve, was
      performed in adult Wistar rats. For 10-112 d post-operation (DPO), half of the
      animals received standard food (placebo) and half received food pellets
      containing 1000 ppm nimodipine, a Ca2+ channel blocker. The time course of
      mimetic reinnervation between these two groups was compared by counting all
      retrogradely labeled motoneurons after injection of horseradish peroxidase (HRP)
      into the whiskerpad. In unoperated animals, injection of HRP labeled 1280 +/- 113
      motoneurons. After FFA, this number dropped to zero, and the first HRP-labeled
      facial motoneurons reappeared in both placebo- and nimodipine-treated animals at
      14 DPO. The treatment with nimodipine yielded two beneficial effects. (1) It
      accelerated axonal sprouting until 28 DPO. Whereas the number of HRP-labeled
      cells in the placebo group was 171 +/- 9 (mean +/- SD) at 16 DPO, 372 +/- 43 at
      21 DPO, and 636 +/- 187 at 28 DPO, the number of sprouted motoneurons in
      nimodipine-treated rats was twice as high: 386 +/- 34 at 16 DPO, 620 +/- 28 at 21
      DPO, and 756 +/- 257 at 28 DPO. (2) Nimodipine reduced the polyneuronal
      innervation of the target muscles. Whereas the number of HRP-labeled cells in the
      placebo group increased to 1430 +/- 36 at 56 DPO and 1600 +/- 31 at 112 DPO, the
      number of labeled motoneurons in nimodipine-treated rats remained almost within
      the normal range: 1315 +/- 31 at 56 DPO and 1354 +/- 33 at 112 DPO.

PMID- 8558233
TI  - Fluctuations in relative levels of choline acetyltransferase mRNA in different
      regions of the rat basal forebrain across the estrous cycle: effects of estrogen
      and progesterone.
AB  - Quantitative in situ hybridization techniques were used to compare relative
      cellular levels of choline acetyltransferase (ChAT) mRNA in different regions of
      the female rat basal forebrain at different stages of the estrous cycle and at
      different time points after the administration of physiological levels of
      estrogen and progesterone. Significant fluctuations in relative levels of ChAT
      mRNA were detected during the course of the estrous cycle. In the medial septum
      (MS) and striatum, the highest levels of ChAT mRNA were detected on diestrus 1.
      Fluctuations in the nucleus basalis magnocellularis (NBM) were highly variable,
      with the highest levels detected on diestrus 2. In ovariectomized animals,
      significant increases in ChAT mRNA were detected in the MS, NBM, and striatum
      within 1-3 d after a single administration of estradiol. In addition, the effects
      of estradiol on ChAT mRNA expression in the NBM and striatum were significantly
      enhanced by the subsequent administration of progesterone. The magnitude and
      timing of the effects of steroid replacement were consistent with the magnitude
      and time course of the fluctuations detected during the course of the estrous
      cycle. These data demonstrate that estrogen and progesterone can increase basal
      forebrain levels of ChAT mRNA significantly in specific regions of the rat basal
      forebrain, that the magnitude and time course of the effects vary between
      different subpopulations of cholinergic neurons, and that the effects are
      associated with changes in the functioning of specific basal forebrain
      cholinergic neurons across the estrous cycle.

PMID- 8558234
TI  - Synapse formation and establishment of neuronal polarity by P19 embryonic
      carcinoma cells and embryonic stem cells.
AB  - A number of different cell lines that exhibit a partial neuronal phenotype have
      been identified, but in many cases the full extent of their neuronal
      differentiation has not been directly addressed by functional studies. We have
      used electrophysiology and immunofluorescence to examine the formation of
      synapses and the development of neuronal polarity by murine embryonic stem (ES)
      cells and the mouse P19 embryonic carcinoma cell line. Within 2-3 weeks after
      induction by retinoic acid, subsets of P19 and ES cells formed excitatory
      synapses, mediated by glutamate receptors, or inhibitory synapses, mediated by
      receptors for GABA or glycine. In ES-cell cultures, both NMDA and non-NMDA
      receptors contributed to the excitatory postsynaptic response. Staining with
      antibodies to growth-associated protein-43 and microtubule-associated protein-2
      revealed segregation of immunoreactivity into separate axonal and somato
      dendritic compartments, respectively. Consistent with our physiological evidence
      for synapse formation, intense punctate staining was observed with antibodies to
      the synaptic vesicle proteins synapsin, SV2, and synaptophysin. These results
      demonstrate the in vitro acquisition by pluri-potent cell lines of neuronal
      polarity and functional synaptic transmission that is characteristic of CNS
      neurons.

PMID- 8558235
TI  - The possible role of hydrogen sulfide as an endogenous neuromodulator.
AB  - Hydrogen sulfide (H2S), which is well known as a toxic gas, is produced
      endogenously from L-cysteine in mammalian tissues. H2S is present at relatively
      high levels in the brain, suggesting that it has a physiological function. Two
      other gases, nitric oxide and carbon monoxide, are also endogenously produced and
      have been proposed as neuronal messengers in the brain. In this work we show the
      following: (1) an H2S-producing enzyme, cystathionine beta-synthase (CBS), is
      highly expressed in the hippocampus; (2) CBS inhibitors hydroxylamine and amino
      oxyacetate suppress the production of brain H2S; and (3) a CBS activator, S
      adenosyl-L-methionine, enhances H2S production, indicating that CBS contributes
      to the production of endogenous H2S. We also show that physiological
      concentrations of H2S selectively enhance NMDA receptor-mediated responses and
      facilitate the induction of hippocampal long-term potentiation. These
      observations suggest that endogenous H2S functions as a neuromodulator in the
      brain.

PMID- 8558236
TI  - Multiple voltage-dependent mechanisms potentiate calcium channel activity in
      hippocampal neurons.
AB  - Neuronal voltage-gated calcium channels provide a pathway for calcium influx that
      is required for processes ranging from intracellular signaling to alterations in
      cellular excitability. In hippocampal neurons, we have characterized a subtype of
      dihydropyridine-sensitive L-type calcium channels (Lp channel) that shows
      multiple kinds of voltage-dependent potentiation of its activity. One type of
      potentiation is elicited by low-voltage stimuli (-10 mV) and can be seen in dual
      pulse protocols in which a transient hyperpolarization is interposed between
      conditioning and test pulses. The second type of potentiation is elicited by much
      higher voltages (+60 mV) and is selectively deactivated at hyperpolarized
      voltages. We have compared these types of potentiation in the Lp channel, the
      "standard" L-type channel, and the cardiac L-type channel. Our results show that
      the high-voltage potentiation is common to all three channel types. The low
      voltage form of potentiation, however, is unique to the Lp channel. Thus, the Lp
      channel shows two kinds of potentiation that differ in their voltage dependence
      and rate of decay. Therefore, calcium channel plasticity in the hippocampus has a
      variety of forms distinguished by their stimulus requirements and duration.

PMID- 8558237
TI  - Immunohistochemical characterization of alterations in the distribution of
      amyloid precursor proteins and beta-amyloid peptide after experimental brain
      injury in the rat.
AB  - Recent reports suggest a relationship between traumatic brain injury and the
      precocious development of neurodegenerative cascades, including diffuse deposits
      of beta-amyloid peptides (A beta) in the injured brain. Because the lateral fluid
      percussion (FP) model of experimental brain injury produces clinically relevant
      neuropathological sequelae in the rat brain, we used this model together with a
      series of antibodies specific for amyloid precursor proteins (APPs), APP-like
      proteins (APLPs), or A beta to identify acute neurodegenerative changes after
      brain trauma. Male Sprague-Dawley rats were anesthetized and subjected to lateral
      FP brain injury of moderate to high severity. At 1 hr, 2 hr, 48 hr, 1 week, or 2
      weeks after injury, animals were killed and their brains were removed for
      immunohistochemical analysis. APP/APLP immunoreactivity increased in specific
      brain regions as early as 1 hr after injury and persisted for at least 2 weeks.
      Axons in the thalamus and subcortical white matter showed the greatest APP/APLP
      accumulation. Injured cortex, striatum, cingulum, and hippocampus also
      demonstrated significant axonal accumulations of APP/APLP. Accumulation of
      APP/APLPs occurred primarily ipsilateral to the injury, although bilateral
      changes were observed in some brain regions. No deposition of A beta was observed
      in any brain region at any time point examined. These results demonstrate a
      pattern of widespread axonal pathology after lateral FP brain injury in the rat,
      characterized by intra-axonal accumulations of APP/APLP immunoreactivity in the
      absence of plaque-like deposits of A beta in the traumatized brain.

PMID- 8558238
TI  - Multipotential stem cells from the adult mouse brain proliferate and self-renew
      in response to basic fibroblast growth factor.
AB  - It has been established that the adult mouse forebrain contains multipotential
      (neuronal/glial) progenitor cells that can be induced to proliferate in vitro
      when epidermal growth factor is provided. These cells are found within the
      subventricular zone of the lateral ventricles, together with other progenitor
      cell populations, whose requirements for proliferation remain undefined. Using
      basic fibroblast growth factor (bFGF), we have isolated multipotential
      progenitors from adult mouse striatum. These progenitors proliferate and can
      differentiate into cells displaying the antigenic properties of astrocytes,
      oligodendrocytes, and neurons. The neuron-like cells possess neuronal features,
      exhibit neuronal electrophysiological properties, and are immunoreactive for
      GABA, substance P, choline acetyl-transferase, and glutamate. Clonal analysis
      confirmed the multipotency of these bFGF-dependent cells. Most significantly,
      subcloning experiments demonstrated that they were capable of self-renewal, which
      led to a progressive increase in population size over serial passaging. These
      results demonstrate that bFGF is mitogenic for multipotential cells from adult
      mammalian forebrain that possess stem cell properties.

PMID- 8558239
TI  - Mutations in shaking-B prevent electrical synapse formation in the Drosophila
      giant fiber system.
AB  - The giant fiber system (GFS) is a simple network of neurons that mediates
      visually elicited escape behavior in Drosophila. The giant fiber (GF), the major
      component of the system, is a large, descending interneuron that relays visual
      stimuli to the motoneurons that innervate the tergotrochanteral jump muscle (TTM)
      and dorsal longitudinal flight muscles (DLMs). Mutations in the neural transcript
      from the shaking-B locus abolish the behavioral response by disrupting
      transmission at some electrical synapses in the GFS. This study focuses on the
      role of the gene in the development of the synaptic connections. Using an
      enhancer-trap line that expresses lacZ in the GFs, we show that the neurons
      develop during the first 30 hr of metamorphosis. Within the next 15 hr, they
      begin to form electrical synapses, as indicated by the transfer of
      intracellularly injected Lucifer yellow. The GFs dye-couple to the TTM motoneuron
      between 30 and 45 hr of metamorphosis, to the peripherally synapsing interneuron
      that drives the DLM motoneurons at approximately 48 hr, and to giant commissural
      interneurons in the brain at approximately 55 hr. Immunocytochemistry with
      shaking-B peptide antisera demonstrates that the expression of shaking-B protein
      in the region of GFS synapses coincides temporally with the onset of
      synaptogenesis; expression persists thereafter. The mutation shak-B2, which
      eliminates protein expression, prevents the establishment of dye coupling shaking
      B, therefore, is essential for the assembly and/or maintenance of functional gap
      junctions at electrical synapses in the GFS.

PMID- 8558241
TI  - Homogeneous development of electrical excitability via heterogeneous ion channel
      expression.
AB  - Synchronous differentiation of delayed-rectifier potassium current regulates
      electrical excitability and calcium entry in motor, sensory, and interneurons of
      the developing amphibian spinal cord. Although Kv1 and Kv2 potassium channel
      transcripts are detectable in these cells, it is not known which transcript
      contributes to functional expression. Overexpression of a Kv1 dominant-negative
      subunit indicates that 20% of neurons have only Kv1 potassium currents. In other
      neurons, non-Kv1 channels function because the dominant-negative subunit either
      only partially suppresses or has no effect on current. Thus, diverse embryonic
      neurons coordinate differentiation of excitability yet rely on heterogeneous
      potassium channel gene expression.

PMID- 8558240
TI  - The onconeural antigen Nova-1 is a neuron-specific RNA-binding protein, the
      activity of which is inhibited by paraneoplastic antibodies.
AB  - Nova-1, a protein expressed in tumors and neurons, is a target antigen in a human
      paraneoplastic motor disorder [paraneoplastic opsoclonus-myoclonus ataxia
      (POMA)]. We evaluated the relationship between the function of Nova-1 and its
      role as a disease antigen. We show that Nova-1 is a neuron-specific RNA-binding
      protein with sequence and functional similarities to FMR-1. Nova-1 mRNA is
      restricted to the subcortical nervous system, and the protein binds to RNA with
      high affinity. Nova-1 KH domains mediate this RNA binding, and point mutations
      within them abrogate binding. POMA disease antisera (6/6) recognize the third KH
      domain but not an inactive point mutant, and affinity-purified antibody blocks
      Nova-1 RNA binding. Thus, a cardinal feature of POMA is the production of
      antibodies that inhibit Nova-1-RNA interactions, suggesting such inhibition may
      cause the neurological disease.

PMID- 8558242
TI  - Postnatal development of membrane properties of layer I neurons in rat neocortex.
AB  - Using whole-cell patch-clamp techniques in brain slices, we studied the postnatal
      development of electrophysiological properties of rat neocortical layer I neurons
      during the first three weeks of postnatal life. Neurons, including Cajal-Retzius
      cells, were visualized under Nomarski optics before recording. In the first
      postnatal week, all layer I neurons, including Cajal-Retzius cells, had low
      resting membrane potentials (-40 to -55 mV), high input resistances (1-5 G
      omega), and long membrane time constants (80-130 msec). Action potentials (APs)
      of layer I neurons early in postnatal development were lower in amplitude and
      longer in duration. The threshold for APs also was more depolarized than in older
      neurons. A medium after-hyperpolarization already was present at postnatal day 0
      (PN0), but fast afterhyperpolarizations were not seen until PN10. At all
      postnatal ages, layer I neurons were capable of repetitive firing, displayed
      little or no frequency adaptation, and did not display slow
      afterhyperpolarizations. Early in development, layer I neurons had a prominent
      hyperpolarization-activation depolarizing sag that decreased with age. These
      results suggest that the membrane properties of rat neocortical layer I neurons
      mature rapidly during the first two postnatal weeks. Cajal-Retzius cells had
      electrical properties similar to other layer I neurons and did not show an
      earlier maturation of membrane properties.

PMID- 8558243
TI  - Essential role of filopodia in chemotropic turning of nerve growth cone induced
      by a glutamate gradient.
AB  - Pathfinding of growing neurites depends on turning of the growth cone in response
      to extracellular cues. Motile filopodia of the growth cone are known to be
      critical for mediating contact-dependent guidance of the growth cone. However,
      whether filopodia also play an essential role in growth cone turning response
      induced by a diffusible chemotropic substance is unclear. Growth cones of
      cultured Xenopus spinal neurons exhibited chemotropic turning responses in a
      gradient of glutamate within a limited range of concentrations. This turning
      response depends on the activation of the NMDA subtype of glutamate receptors and
      requires the presence of extracellular Ca2+. Time-lapse differential interference
      contrast microscopy with quantitative analysis of filopodia dynamics showed a
      close correlation between an increased number of filopodia on the side of the
      growth cone facing the glutamate source and the turning. Such filopodia asymmetry
      was observed within minutes after the onset of the glutamate gradient, before any
      detectable turning of the growth cone. In Ca(2+)-free medium, no filopodia
      asymmetry was induced by the glutamate gradient, and no growth cone turning was
      observed. Furthermore, elimination of filopodia with a low concentration of
      cytochalasin B completely abolished the turning response without substantially
      affecting neurite extension. Thus, filopodia may be required for chemotropic
      guidance of the growth cone, and an asymmetry in filopodia distribution may be an
      early cellular event responsible for determining the direction the growth cone
      advances.

PMID- 8558244
TI  - Cell cycle blockers mimosine, ciclopirox, and deferoxamine prevent the death of
      PC12 cells and postmitotic sympathetic neurons after removal of trophic support.
AB  - In the present study, we tested whether apoptotic neuronal death caused by
      withdrawal of trophic support might be prevented by agents that block cell cycle
      progression. We used three complementary model systems that exhibit apoptotic
      death: dividing PC12 cells deprived of nerve growth factor (NGF); and primary
      cultures of postmitotic sympathetic neurons deprived of NGF. We show that cell
      death in each case can be suppressed by treatment with the G1/S blockers
      mimosine, ciclopirox, and deferoxamine at concentrations that correlate with
      their abilities to block PC12 cell proliferation. In contrast, agents that block
      cell cycle progression in the S-, G2-, or M-phase do not prevent cell death.
      These observations support the hypothesis that removal of trophic support from
      dividing or postmitotic neuronal cells provokes their apoptotic death by causing
      them either to proceed through or to attempt to re-enter an uncoordinated and
      consequently fatal cell cycle. Moreover, the data suggest that simply blocking
      the cycle at any point is not protective but, rather, that it is necessary to
      block at specific "safe" points. This study defines a safe point in the cell
      cycle before the G1/S transition that is demarcated by the action of these three
      agents.

PMID- 8558245
TI  - Analysis of integrin expression on oligodendrocytes during axo-glial interaction
      by using rat-mouse xenocultures.
AB  - To analyze the expression of cell-surface molecules on neurons or glia during
      myelination, we have developed a xenotypic coculture system in which mouse
      oligodendrocytes interact with rat dorsal root ganglion neurons. The axo-glial
      interactions in these cultures promote oligodendrocyte precursor cell
      proliferation, survival, and differentiation as in vivo, thus supporting the
      validity of the xenocultures as a model system to study myelination in which the
      molecules on the neurons or the glia can be distinguished using species-specific
      antibodies. We examined the expression of integrins, the major family of cell
      surface extracellular matrix receptors, on oligodendrocytes during the early
      stages of myelination and found that, unlike Schwann cells, oligodendrocytes do
      not express alpha 6 beta 4 in association with myelin sheath formation. The
      pattern of integrin expression observed on oligodendrocytes in these cultures is
      similar to that seen in oligodendrocytes that differentiate in purified cultures,
      and it comprises alpha 6 beta 1, alpha v beta 5, and an as yet uncharacterized
      alpha v-associated beta subunit of 80 kDa. Changes in integrin expression
      associated with differentiation, therefore, do not depend on axonal contact, and
      beta 4 is not required for myelin sheath formation, although its expression may
      contribute to the individual properties of oligodendrocytes and Schwann cells.

PMID- 8558246
TI  - Muscimol acts in dorsomedial but not paraventricular hypothalamic nucleus to
      suppress cardiovascular effects of stress.
AB  - Both the dorsomedial hypothalamic nucleus (DMH) and the paraventricular
      hypothalamic nucleus (PVN) have been implicated in the neural control of the
      cardiovascular response to stress. We used the GABAA agonist muscimol to inhibit
      neuronal activation and attempted to identify hypothalamic nuclei required for
      the cardiovascular response to air stress. Chronically instrumented rats received
      bilateral injections of either 80 pmol of muscimol or 100 nl of saline vehicle
      into the DMH, the PVN, or an intermediate area (including the rostral edge of the
      DMH and the region between the two nuclei) and were placed immediately in a
      restraining tube and subjected to 20 min of air stress. In all rats, air stress
      after vehicle injections caused marked increases in heart rate (137 +/- 6
      beats/min) and blood pressure (26 +/- 2 mmHg). Microinjection of muscimol into
      the DMH suppressed the heart rate and blood pressure response by 85 and 68%,
      respectively. Identical microinjection of muscimol into the intermediate area
      between the DMH and the PVN attenuated the increases in heart rate by only 46%
      and in blood pressure by 52%. In contrast, similar injections into the vicinity
      of the PVN failed to alter the cardiovascular response to air stress. These
      findings demonstrate that muscimol-induced inhibition of neuronal activity in the
      region of the DMH blocks air stress-induced increases in heart rate and arterial
      pressure, whereas similar treatment in the area of the PVN has no effect.

PMID- 8558247
TI  - Functional morphology of the feedback pathway from area 17 of the cat visual
      cortex to the lateral geniculate nucleus.
AB  - Two approaches were adopted to study the pattern of connectivity between the cat
      visual cortex and lateral geniculate nucleus. Fourteen individual cortico
      geniculate axons were labeled and reconstructed after intracellular or
      extracellular injection of biocytin into regions of known receptive-field
      position and ocular dominance preference, and the distribution of boutons from
      multi-axon clusters was mapped in three dimensions and compared with the
      locations of strategically placed geniculate recordings made in the same tissue.
      The results show that the feedback has an accurate retinotopic component but that
      individual axons are both more extensive and more selective than described
      previously. Area 17 feedback axons terminate primarily in layers A and A1, but
      the distribution of terminal boutons is strongly biased (3:1 ratio) toward the
      layer that matches their eye preference. Thus, those driven by the contralateral
      eye preferentially target layer A, and those driven by the ipsilateral eye target
      layer A1. Each axon also innervates the perigeniculate nucleus (PGN), but the
      pattern is otherwise variable, suggesting that there are different axonal
      classes. The terminal fields of individual axons are much larger than described
      previously, with a maximum spread of 500-1500 microns. Nevertheless, the
      projection from a given location in area 17 has a center of maximum terminal
      density 400-500 microns across, which is in retinotopic correspondence with the
      aggregate receptive field of the cortical cells of origin. The surrounding zone
      of relatively sparse boutons, however, must permit corticofugal cells to
      influence visual processing well beyond the regions over which their own
      responses summate. It follows that any geniculate cell receives corticofugal
      input covering an equally extensive area of visual space.

PMID- 8558248
TI  - Potentiation of neuronal NMDA response induced by dehydroepiandrosterone and its
      suppression by progesterone: effects mediated via sigma receptors.
AB  - We have shown previously that low doses of selective sigma (sigma)-receptor
      ligands potentiate the excitatory response of pyramidal neurons to NMDA in the
      CA3 region of the dorsal hippocampus in the rat. Because progesterone
      competitively displaces the binding of the ligand N-[3H]allyl-normetazocine (SKF
      10,047), the present studies were undertaken to determine in vivo the effect of
      neuroactive steroids on NMDA-induced excitation of rat CA3 pyramidal neurons. Low
      doses of dehydroepiandrosterone (DHEA) potentiated the NMDA response selectively
      and dose-dependently. The effect of DHEA was reversed by the selective sigma
      antagonist N-dipropyl-2-(4-methoxy-3- (2-phenylethoxy)phenyl)-ethylamine
      monohydrochloride (NE-100) and by haloperidol, but not by spiperone. Progesterone
      had no effect by itself but reversed, at low doses, the potentiation of the NMDA
      response induced by DHEA as well as those induced by nonsteroidal sigma ligands.
      Neither pregnenolone nor pregnenolone sulfate had any effect on the NMDA response
      -nor did they antagonize the potentiation of the NMDA response induced by DHEA
      and by nonsteroidal sigma ligands. A pertussis toxin pretreatment, which
      inactivates Gi/o-proteins, abolished the potentiating effects of DHEA.
      Ovariectomy enhanced the potentiation of the NMDA response by the nonsteroidal
      sigma ligand di(2-tolyl)guanidine (DTG). There was a reciprocal occlusion of the
      effects of DHEA and DTG; DTG did not potentiate the NMDA response further after
      DHEA, and DHEA did not do so after DTG. These results suggest that some
      neuroactive steroids modulate the NMDA response via sigma receptors.

PMID- 8558249
TI  - Specificity in the axonal connections of layer VI neurons in tree shrew striate
      cortex: evidence for distinct granular and supragranular systems.
AB  - Pyramidal neurons in layer VI of striate cortex are the source of descending
      projections to the lateral geniculate nucleus (LGN) as well as a major source of
      axon terminals in the layers of striate cortex that receive LGN projections. This
      study examines how the connections of layer VI neurons are arranged with respect
      to the functionally distinct classes of neurons that compose their cortical and
      subcortical targets. By placing injections of biocytin into layer VI of tree
      shrew striate cortex, we identified two sublayers that differ in their
      intracortical and thalamic connections. Neurons in the upper part of layer VI,
      layer VIa, terminate in cortical layer IV, whereas those in the lower part of
      layer VI, layer VIb, terminate throughout the supragranular layers, layers I-III.
      The selectivity of layer VI subdivisions for the granular and supragranular
      layers is also evident in their descending projections. Neurons in layer VIa
      terminate preferentially in the LGN layers that supply layer IV (LGN layers 1, 2,
      4, and 5), whereas neurons in layer VIb terminate in the LGN layers that supply
      layers I-III (LGN layers 3 and 6) and in the pulvinar nucleus. Additional
      subclasses of layer VIa neurons were identified based on the restriction of their
      terminal fields to narrow subtiers within layer IV. By influencing the activity
      of distinct populations of cortical neurons and the thalamic neurons that supply
      them, layer VI neurons could exert a powerful influence on the flow of activity
      in functionally distinct cortical circuits.

PMID- 8558250
TI  - The effect of depressing glial function in rat brain in situ on ion homeostasis,
      synaptic transmission, and neuron survival.
AB  - The supporting role of glial cells in maintaining neurons and in ion homeostasis
      has been studied in situ by perfusing the gliotoxin fluorocitrate (FC) through a
      microdialysis fiber in the CA1 area of urethane-anesthetized rats. Extracellular
      direct current potential, extracellular potassium concentration ([K+]o) and amino
      acid levels, extracellular pH (pHo), and evoked field activity were studied.
      Histology verified the swelling of glial cells after 4 hr of FC treatment.
      Massive neuron damage was evident after 8 hr. FC dialysis caused the rapid
      decrease of glutamine, pHo became progressively more acid, and [K+]o moderately
      elevated. Orthodromic transmission was variably blocked within 30 min to 4 hr.
      After 4 hr, spreading depression (SD) waves that originated from the neocortex
      invaded hippocampal CA1, [K+]o increased to higher levels, pHo became very acid,
      and there were steep increases in taurine, glutamate, and GABA levels.
      Simultaneously, the antidromic population spike (a-PS) became depressed and
      eventually disappeared. When a shorter dialysis probe that spared cortex was used
      to sample CA1, no SD was seen, a-PS was not abolished, and ion homeostasis was
      altered less markedly. Repeated SD provoked in hippocampus in the absence of FC
      caused only mild depression of a-PS. Dialysis of high-K+ solution in healthy
      neocortex or hippocampus caused only slight elevation of [K+]o at distances of
      200-400 microns from the dialysis membrane. After treatment with FC, similar high
      K+ dialysis raised [K+]o much more. We conclude the following: (1) recurrent SD
      waves injure neurons if and only if glial function has failed; (2) neurons can
      regulate [K+]o, albeit imperfectly; (3) glia is required for the normal fine
      tuning of [K+]o and particularly for the recovery of pathologically elevated
      [K+]o; and (4) glia are required for the regulation of pHo. The similarities
      between glial poisoning by FC and the reported changes in the penumbra of
      ischemic infarcts suggest that the extension of neuron loss into the penumbral
      region might depend on failure of glial protection.

PMID- 8558251
TI  - Cocaine alters cerebral metabolism within the ventral striatum and limbic cortex
      of monkeys.
AB  - The functional consequences of acute cocaine administration in nonhuman primates
      were assessed using the quantitative 2-[14C]deoxyglucose method. Local rates of
      cerebral metabolism were determined after an intravenous infusion of 1.0 mg/kg
      cocaine or vehicle in six awake cynomolgus monkeys (Macaca fascicularis) trained
      to sit calmly in a primate chair. Cocaine administration decreased glucose
      utilization in a discrete set of structures that included both cortical and
      subcortical portions of the limbic system. Glucose metabolism in the core and
      shell of the nucleus accumbens was decreased markedly, and smaller decrements
      were observed in the caudate and anterior putamen. In addition, cocaine
      administration produced significant decreases in limbic cortex. Metabolism was
      decreased in orbitofrontal cortex (areas 11, 12o, 13, 13a, 13b), portions of the
      gyrus rectus including area 25, entorhinal cortex, and parts of the hippocampal
      formation. The cortical regions in which functional activity was altered provide
      dense projections to the nucleus accumbens, and the decreased activity in these
      projections may be responsible in part of the large alterations in functional
      activity within the ventral striatum. Decreased metabolism also was evident in
      the anterior nuclear group of the thalamus, raphe nuclei, and locus ceruleus. The
      acute cerebral metabolic effects of cocaine in the conscious macaque, therefore,
      were contained primarily within a set of interconnected limbic regions, including
      ventral prefrontal cortex, medial temporal regions, the ventral striatal complex,
      and anterior thalamus. The decreased rates of glucose metabolism reported here
      resemble decrements found using positron emission tomography in humans. In the
      rat, by contrast, metabolic activity increased and changes were focused in
      subcortical regions. The present results represent an important expansion of the
      neural circuitry on which cocaine acts in the monkey as compared with the rat,
      and this in turn implies that cocaine affects a broader spectra of behaviors in
      primates than in rodents.

PMID- 8558252
TI  - Intracellular dialysis of cyclic nucleotides induces inward currents in turtle
      vomeronasal receptor neurons.
AB  - Turtle vomeronasal receptor neurons in slice preparations were studied using the
      patch-clamp technique in the whole-cell and cell-attached configurations. The
      mean resting potential was -48, and the response to an injected current step
      consisted of either a single spike or a train of spikes. An injected current of 3
      30 pA was required to depolarize the neuron to spike threshold near -50 mV.
      Voltage-clamped vomeronasal receptor neurons displayed transient inward currents
      followed by sustained outward currents in response to depolarizing voltage steps.
      In cell-attached recordings, 10 microM forskolin added to the bath caused a
      transient increase of spike rate. Intracellular application of cAMP evoked ann
      inward current in a dose-dependent manner from the neurons voltage clamped at -70
      mV; 0.1 mM cAMP was sufficient to elicit an inward current in the neurons. The
      magnitude of the response to cAMP reached a plateau at 1 mM with an average peak
      amplitude of 176 +/- 34 pA. Intracellular application of 1 mM cGMP also evoked an
      inward current with an average peak amplitude of 227 +/- 61 pA. The reversal
      potentials of the induced components were estimated to be 10 +/- 7 mV for cAMP
      and -4 +/- 16 mV for cGMP. The reversal potential of the cAMP-induced current in
      external Cl(-)-free solution was similar to that in normal Ringer's solution,
      suggesting that Cl- current is not significantly involved in the current. The
      present results represent the first evidence of cyclic nucleotide-activated
      conductance in the vomeronasal receptor membranes.

PMID- 8558253
TI  - Altered inhibition of dentate granule cells during spatial learning in an
      exploration task.
AB  - To investigate the extent to which inhibitory interneurons control impulse flow
      through the dentate gyrus during spatial learning in an exploration task, dentate
      field potentials were recorded in response to paired stimulation of the perforant
      path while rats rested or explored. Recurrent inhibition of the granule cells was
      measured as the reduction of the second waveform when a population spike was
      present in the first. Both the population spike and the field EPSP (fEPSP) were
      suppressed at interstimulus intervals shorter than approximately 40 msec.
      Consistent differences were observed between potentials recorded at equivalent
      brain temperature in the exploration and resting (reference) conditions. During
      exploration, the fEPSP of the second (test) waveform was reduced further compared
      with reference potentials with a similar response to the first (conditioning)
      stimulus. This reduction was observed only when the first pulse elicited a
      population spike. The population spike of the second waveform was facilitated
      compared with reference potentials with similar fEPSP slopes. These observations
      suggest that exploration is coupled to increased inhibition on the perforant-path
      terminals or the dendrites of the granule cells, whereas the inhibition on the
      somata is decreased. The two phenomena were not correlated and followed different
      time courses. The suppression of the fEPSP decayed gradually, although it was
      still present at 15 min, whereas the facilitation of the population spike was
      stable. Together, these changes, which likely involve different populations of
      interneurons, may focus and amplify incoming signals from the entorhinal cortex.

PMID- 8558254
TI  - Dorsal spinocerebellar tract neurons in the chronic intact cat during wakefulness
      and sleep: analysis of spontaneous spike activity.
AB  - Relatively little is known about the transmission of ascending sensory
      information from lumbar levels across the behavioral states of sleep and
      wakefulness. The present study used extracellular recording methods in
      chronically instrumented intact behaving cats to monitor the activity of lumbar
      dorsal spinocerebellar tract (DSCT) neurons within Clarke's column during the
      states of wakefulness, quiet sleep, and active sleep. Clarke's column DSCT
      neurons were identified using antidromic identification and retrograde labeling
      techniques. The spontaneous spike rate and interspike interval data of DSCT
      neurons were quantified as a function of behavioral state. During wakefulness and
      quiet sleep, the spike rate of DSCT neurons was stable, and interspike interval
      histograms (ISIH) indicated a relatively high degree of regularity in DSCT
      neuronal spike train patterns. In contrast, during active sleep there was a
      marked reduction in the ongoing spike rate in a vast majority of cells tested.
      The magnitude of change in ISIHs and interspike interval data during active sleep
      depended in part on whether the reduction in cell firing was maintained or
      periodic throughout active sleep. Further suppression of spontaneous activity
      also was observed during intense rapid-eye-movement episodes of active sleep that
      were associated with clustered pontogeniculo-occipital wave and muscular twitches
      and jerks. After re-awakening, spontaneous spike activity of Clarke's column DSCT
      neurons resembled that recorded during previous episodes of wakefulness. These
      data provide evidence that ascending proprioceptive and exteroceptive sensory
      transmission through Clarke's column is diminished during the behavioral state of
      active sleep.

PMID- 8558255
TI  - Changes of synaptic efficacy in the medial geniculate nucleus as a result of
      auditory classical conditioning.
AB  - In this study we examined inputs to neurons in the medial subnucleus of the
      medial geniculate nucleus (mMG) for changes of synaptic efficacy associated with
      heart-rate conditioning to an auditory conditioned stimulus (CS). Conditioning
      related changes of synaptic efficacy were measured in awake animals by examining
      mMG single-unit responses evoked by stimulation of one of two areas that send
      auditory CS and nonauditory information monosynaptically to the mMG, the brachium
      of the inferior colliculus (BlC) and the superior colliculus (SC). Synaptic
      efficacy was measured before, immediately after, and 1 hr after one session of
      classical conditioning with a tone CS and a corneal airpuff unconditioned
      stimulus. To determine whether conditioning produced changes of synaptic efficacy
      on the auditory BlC inputs to mMG cells and not general changes of cellular
      excitability, analyses of synaptic efficacy were performed on the mMG units that
      exhibited short-latency evoked responses (< 3.5 msec) to both BlC and SC
      stimulation. Analyses revealed that the BlC but not the SC test stimulus-evoked
      unit activity from the same neurons exhibited the following changes immediately
      after conditioning: decreases in unit response latency, increases in unit
      response reliability, and increases in spike frequency. BlC-evoked unit responses
      after pseudoconditioning did not exhibit these changes in unit responding. These
      results suggest that the synapses carrying auditory CS information to mMG neurons
      increase in strength as the result of associative conditioning with an acoustic
      CS. Some of these changes of synaptic efficacy remained 1 hr after training.

PMID- 8558256
TI  - Metabolic coupling between glia and neurons.

PMID- 8558257
TI  - Fibroblast growth factor-2 protects entorhinal layer II glutamatergic neurons
      from axotomy-induced death.
AB  - The entorhinal cortex is a major relay between the hippocampus and other cortical
      and subcortical regions. Glutamatergic axons from layer II neurons form the
      entorhinal cortical projection to the hippocampus via the perforant pathway. We
      have demonstrated previously that lesion of the perforant pathway causes the
      death of approximately 30% of entorhinal layer II (ECL2) neurons. To elucidate
      mechanisms contributing to neuronal death and to investigate strategies
      preventing it, we identified the phenotype of the vulnerable neuronal population.
      Sections were immunolabeled with antibodies to the neuronal markers NeuN,
      glutamate, and calbindin-D28k, and to receptors for fibroblast growth factor-2
      (FGFR1) and NMDA (NMDAR1) and were examined using confocal microscopy. Calbindin
      immunoreactivity was strikingly lamina-specific to ECL2, where one-third of all
      ECL2 neurons were calbindin-positive. Localization of glutamate revealed that
      half of the glutamatergic ECL2 neurons coexpressed calbindin. Quantification
      using unbiased stereology at 9 weeks after lesion of the perforant pathway
      revealed that the only ECL2 neuronal population that experienced a significant
      (70%) loss (20% of the total) was the population of glutamatergic ECL2 neurons
      that did not coexpress calbindin. All ECL2 neurons expressed FGFR1; therefore, we
      tested the role of FGF-2 in the survival of glutamatergic ECL2 neurons. We
      grafted fibroblasts genetically engineered to express nerve growth factor or FGF
      2 and found that only FGF-2 grafts prevented loss of the vulnerable
      glutamatergic/calbindin-negative neurons. We present a hypothesis for the
      selective vulnerability of these glutamatergic/calbindin-negative ECL2 neurons
      and address the role of FGF-2 in neuronal rescue.

PMID- 8558258
TI  - Amyloidogenic processing of the human amyloid precursor protein in primary
      cultures of rat hippocampal neurons.
AB  - The aim of this study was to investigate the proteolytic processing of the
      amyloid precursor protein (APP) in polarized primary cultures of hippocampal
      neurons. We have used the Semliki Forest virus (SFV) vector to express human
      APP695 in hippocampal neurons, sympathetic ganglia, and glial cells. The latter
      two cells secrete little or no APP, whereas hippocampal neurons secrete two forms
      of APP695, which differ in sialic acid content and in their kinetic appearance in
      the culture medium. In addition, rat hippocampal neurons expressing human APP
      produced significant amounts of the 4 kDa peptide beta A4. After 3 hr of
      metabolic labeling, the relative amount of beta A4 peptide to total cellular APP
      was 5.3%. Fibroblasts expressing APP695 using the same SFV vector mainly produced
      a related 3 kDa p3 peptide, a nonamyloidogenic fragment. Remarkably, the
      hippocampal neurons also produced significant amounts of beta A4-containing C
      terminal fragments (10-12 kDa) intracellularly. Radiosequencing showed that these
      fragments were created at a previously described beta-secretase cleavage site and
      at a cleavage site 12 residues from the N terminus of the beta A4 domain (Thr584
      of APP695), which we named delta-cleavage. Based on the observation that mature
      hippocampal neurons produce two potentially amyloidogenic fragments and secrete
      substantial amounts of beta A4 when expressing human APP, our results strengthen
      the hypothesis that neurons play a central role in the process of beta A4
      deposition in cases of Alzheimer's disease and in aged primates.

PMID- 8558259
TI  - Sensory transduction in vomeronasal neurons: evidence for G alpha o, G alpha i2,
      and adenylyl cyclase II as major components of a pheromone signaling cascade.
AB  - The mammalian vomeronasal organ (VNO) is an accessory olfactory structure
      implicated in the sensing of pheromones. Although virtually nothing is known
      about sensory transduction in the mammalian VNO, recent findings have raised the
      possibility that it proceeds via a G-protein-coupled mechanism and involves a
      cyclic nucleotide-gated ion channel as in the nasal olfactory epithelium. To
      investigate this possibility, we cloned G-protein alpha subunits, adenylyl
      cyclases, and guanylyl cyclases that are expressed in the VNO and examined their
      patterns of expression. Of seven G alpha subunits identified as being expressed
      in the VNO, we found that mRNAs encoding only two, G alpha o and G alpha i2, are
      highly expressed in VNO neurons. Moreover, G alpha o and G alpha i2 are highly
      expressed by separate subsets of neurons that are located in different regions of
      the VNO neuroepithelium. Immunohistochemical studies show that both G alpha o and
      G alpha i2 are enriched in VNO microvilli, suggesting that G-proteins containing
      both of these alpha subunits may be involved in VNO sensory transduction. Of the
      adenylyl and guanylyl cyclases that we cloned, we found that only one, adenylyl
      cyclase type II, is highly expressed in VNO neurons; furthermore, it is expressed
      by both G alpha o+ and G alpha i2+ subsets. Our findings suggest that spatially
      segregated subsets of VNO neurons may use different, but related, sensory
      transduction pathways in which G-proteins and an adenylyl cyclase play major
      roles.

PMID- 8558260
TI  - Vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide,
      and noradrenaline induce the transcription factors CCAAT/enhancer binding protein
      (C/EBP)-beta and C/EBP delta in mouse cortical astrocytes: involvement in cAMP
      regulated glycogen metabolism.
AB  - We have described previously a transcription-dependent induction of glycogen
      resynthesis by the vasoactive intestinal peptide (VIP) or noradrenaline (NA) in
      astrocytes, which is mediated by cAMP. Because it has been postulated that the
      cAMP-mediated regulation of energy balance in hepatocytes and adipocytes is
      channeled at least in part through the CCAAT/enhancer binding protein (C/EBP)
      family of transcription factors, we tested the hypothesis that C/EBP isoforms
      could be expressed in mouse cortical astrocytes and that their level of
      expression could be regulated by VIP, by the VIP-related neuropeptide pituitary
      adenylate cyclase-activating peptide (PACAP), or by NA. We report in this study
      that in these cells, C/EBP beta and C/EBP delta are induced by VIP, PACAP, or NA
      via the cAMP second-messenger pathway. Induction of C/EBP beta and -delta mRNA by
      VIP occurs in the presence of a protein synthesis inhibitor. Thus, c/ebp beta and
      c/ebp delta behave as cAMP-inducible immediate-early genes in astrocytes.
      Moreover, transfection of astrocytes with expression vectors selectively
      producing the transcriptionally active form of C/EBP beta, termed liver-enriched
      transcriptional activator protein, or C/EBP delta enhance the glycogen
      resynthesis elicited by NA, whereas an expression vector producing the
      transcriptionally inactive form of C/EBP beta, termed liver-enriched
      transcriptional inhibitory protein, reduces this resynthesis. These results
      support the idea that C/EBP beta and -delta regulate gene expression of energy
      metabolism-related enzymes in astrocytes.

PMID- 8558262
TI  - DNA mismatch repair and DNA methylation in adult brain neurons.
AB  - DNA repair is essential for maintaining the integrity of the nucleotide sequence
      of cellular DNA over time. Although much information has accumulated recently on
      the mechanisms of DNA repair in cultured cells, little is known about the DNA
      repair capabilities of cells in the adult brain. In the present study, we have
      investigated the capacity of nuclear extracts from adult rodent brain neurons to
      carry out DNA mismatch repair. We focused on the repair of G.T and G.U
      mismatches, which are caused by deamination of 5-methyl cytosine to thymine, or
      cytosine to uracil, respectively, because these are the only types of mismatches
      that can arise in nondividing cells. We found that nuclear extracts from adult
      brain neurons can correct G.T and G.U mismatches, restoring them to G:C base
      pairs. Several other types of DNA mismatches could not be processed. These data
      provide the first direct demonstration that neurons in the adult mammalian brain
      have the capability to carry out DNA mismatch repair. We also we report that
      adult brain contains high levels of DNA methyltransferase (MTase) activity. We
      propose that one function of DNA MTase in the adult brain is to remethylate newly
      incorporated cytosine residues from G.T mismatch repair after deamination of 5
      methyl cytosine, thereby maintaining the original pattern of DNA methylation. The
      high levels of brain DNA MTase suggest further that this enzyme has additional
      functions in the brain.

PMID- 8558261
TI  - A G-protein-activated inwardly rectifying K+ channel (GIRK4) from human
      hippocampus associates with other GIRK channels.
AB  - Transcripts of a gene, GIRK4, that encodes for a 419-amino-acid protein and shows
      high structural similarity to other subfamily members of G-protein-activated
      inwardly rectifying K+ channels (GIRK) have been identified in the human
      hippocampus. When expressed in Xenopus oocytes, GIRK4 yielded functional GIRK
      channels with activity that was enhanced by the stimulation of coexpressed
      serotonin 1A receptors. GIRK4 potentiated basal and agonist-induced currents
      mediated by other GIRK channels, possibly because of channel heteromerization.
      Despite the structural similarity to a putative rat KATP channel, no ATP
      sensitivity or KATP-typical pharmacology was observed for GIRK4 alone or GIRK4
      transfected in conjunction with other GIRK channels in COS-7 cells. In rat brain,
      GIRK4 is expressed together with three other subfamily members, GIRK1-3, most
      likely in identical hippocampal neurons. Thus, heteromerization or an unknown
      molecular interaction may cause the physiological diversity observed within this
      class of K+ channels.

PMID- 8558263
TI  - Axons regulate the distribution of Schwann cell microtubules.
AB  - It is well established that axons regulate Schwann cell phenotype. The purpose of
      the present study was to determine whether axons influence the arrangement of
      Schwann cell microtubules (MTs). Using double-labeling immunocytochemistry and
      confocal microscopy, we show that MTs in undifferentiated Schwann cells are
      nucleated from and attached to a single MT organizing center (MTOC) that is
      associated with the centrosome. Physical contact with appropriate axons initiates
      a myelin-forming phenotype that disperses MT minus ends and induces multiple MT
      nucleating sites in Schwann cell perinuclear cytoplasm. The axonal signal that
      initiates myelin breakdown during Wallerian degeneration induces multiple MTOCs
      and MT bundles in Schwann cell perinuclear cytoplasm and in cytoplasm between
      degenerating myelin ovoids. These results establish that axons influence Schwann
      cell MT distribution by regulating the location and number of MT-nucleation
      sites.

PMID- 8558264
TI  - Distribution of high-conductance Ca(2+)-activated K+ channels in rat brain:
      targeting to axons and nerve terminals.
AB  - Tissue expression and distribution of the high-conductance Ca(2+)-activated K+
      channel Slo was investigated in rat brain by immunocytochemistry, in situ
      hybridization, and radioligand binding using the novel high-affinity (Kd 22 pM)
      ligand [3H]iberiotoxin-D19C ([3H]IbTX-D19C), which is an analog of the selective
      maxi-K peptidyl blocker IbTX. A sequence-directed antibody directed against Slo
      revealed the expression of a 125 kDa polypeptide in rat brain by Western blotting
      and precipitated the specifically bound [3H]IbTX-D19C in solubilized brain
      membranes. Slo immunoreactivity was highly concentrated in terminal areas of
      prominent fiber tracts: the substantia nigra pars reticulata, globus pallidus,
      olfactory system, interpeduncular nucleus, hippocampal formation including mossy
      fibers and perforant path terminals, medial forebrain bundle and pyramidal tract,
      as well as cerebellar Purkinje cells. In situ hybridization indicated high levels
      of Slo mRNA in the neocortex, olfactory system, habenula, striatum, granule and
      pyramidal cell layer of the hippocampus, and Purkinje cells. The distribution of
      Slo protein was confirmed in microdissected brain areas by Western blotting and
      radioligand-binding studies. The latter studies also established the
      pharmacological profile of neuronal Slo channels. The expression pattern of Slo
      is consistent with its targeting into a presynaptic compartment, which implies an
      important role in neural transmission.

PMID- 8558265
TI  - Proneuropeptide Y processing in large dense-core vesicles: manipulation of
      prohormone convertase expression in sympathetic neurons using adenoviruses.
AB  - The efficient delivery of foreign genes into postmitotic cells is becoming very
      important for studies of nervous system functions. Cultured sympathetic neurons
      synthesize neuropeptide Y (NPY) in addition to catecholamines, providing an
      experimental model for studying neuronal peptide biosynthesis. In this work, we
      have studied the biosynthetic processing of NPY in primary cultures of rat
      superior cervical ganglion (SCG) neurons. NPY activation is complex, requiring
      sequential actions of a prohormone convertase (PC), carboxypeptidase H, and
      peptidylglycine alpha-amidating mono-oxygenase. Northern analyses established
      that SCG neurons in the animal contain mRNAs for both PC1 and PC2, and
      simultaneous immunocytochemistry for NPY and PC1 or PC2 established a 1:1
      correspondence between NPY and PC2 expression in two thirds of the neurons that
      express NPY, both in the animal and in tissue culture. Biosynthetic studies on
      proneuropeptide Y (pro-NPY) processing to mature NPY established a close
      similarity to the rates seen in endocrine cells expressing PC2 and established
      clear differences between the patterns in SCG neurons and in endocrine cells
      expressing PC1. Recombinant adenoviruses were used to increase the level of PC1
      in the cultured neurons from negligible to a level comparable with the level of
      PC1 in the anterior pituitary, and pro-NPY processing was markedly accelerated.
      When the viruses were used to lower the endogenous PC2 levels, using an antisense
      construct, pro-NPY processing was retarded. Taken together, these results support
      a major role for PC2 as the pro-NPY converting enzyme, and they establish the
      cultured SCG neurons as a model to study neuronal peptide biosynthesis.

PMID- 8558266
TI  - Colocalization of GABA, glycine, and their receptors at synapses in the rat
      spinal cord.
AB  - To determine whether GABA and glycine can act as cotransmitters at synapses in
      the rat spinal cord, we have compared the ultrastructural distribution of GABAA
      receptor beta 3 subunit with that of the glycine receptor-associated protein
      gephyrin and combined this with postembedding detection of GABA and glycine. We
      also used a dual-immunofluorescence method to confirm that gephyrin was
      associated with the glycine-receptor alpha 1 subunit throughout the cord. GABAA
      beta 3-subunit immunoreactivity was restricted primarily to synapses, and at a
      majority of these synapses the presynaptic axon was GABA-immunoreactive. Many
      synapses showed both GABAA beta 3 and gephyrin immunoreactivity, and at most of
      these synapses GABA and glycine were enriched in the presynaptic axon. These
      results strongly support the idea that cotransmission by GABA and glycine occurs
      in the spinal cord.

PMID- 8558267
TI  - Activity-dependent short-term enhancement of intercellular coupling.
AB  - It was reported previously that repeated brief tetanization of the posterior
      eight nerve can produce long-term homosynaptic potentiations of the electrotonic
      and chemical components of the mixed EPSP evoked in the Mauthner cell lateral
      dendrite by a single stimulus to the nerve. We show here that the same stimulus
      paradigm can lead, alternatively, to short-term enhancements of both excitatory
      responses. These transient modifications last for approximately 3 min, with a
      time course similar to post-tetanic potentiation at chemical synapses. However, a
      different stimulus pattern that transiently increases the presynaptic calcium
      concentration, paired-nerve stimuli, does not have any significant effect on
      electrotonic transmission, whereas it facilitates the chemically mediated EPSP.
      On the other hand, induction of the short-lasting potentiation of coupling, which
      depended on the discontinuous or burst-like property of the tetanizing paradigm,
      required NMDA-receptor activation and was blocked by postsynaptic intradendritic
      injections of the calcium chelator bis(2-aminophenoxy)ethane-N,N,N',N'-tetra
      acetic acid. The ineffectiveness of presynaptic calcium in potentiating
      electrotonic coupling likely reflects the involvement of a calcium-dependent
      regulatory protein in the postsynaptic cell and suggests that hemichannels on the
      two sides of a gap junction plaque can be modified independently. NMDA-mediated
      modulation of gap junctions could be widespread, because both types of channels
      coexist during development and in several mammalian adult central nervous system
      structures such as hippocampus.

PMID- 8558268
TI  - In vitro analysis of optimal stimuli for phase-locking and time-delayed
      modulation of firing in avian nucleus laminaris neurons.
AB  - Neurons of the avian nucleus laminaris (NL) provide a neural substrate for
      azimuthal sound localization. We examined the optimal stimuli for NL neurons to
      maintain high discharge rates, reliable phase-locking, and sensitivity to time
      delayed stimuli. Whole-cell recordings were performed in chick [embryonic days 19
      21 (E19-E21)] NL neurons using an in vitro slice preparation. Variation of
      membrane properties along the tonotopic axis was examined. Computer-controlled
      intracellular current injection was used to mimic postsynaptic currents or
      conductances (PSCs) generated in NL neurons by the firing of nucleus
      magnocellularis (NM) neurons during acoustic stimulation. At various stimulus
      frequencies, the effects of varying the number of NM cells and PSC amplitudes on
      firing rate and phase-locking were examined. During high-frequency stimulation,
      the greatest firing rate and phase-locking occurred when the protocol contained
      few NM cells that generated large PSCs. Because the stimulus-evoked unitary PSCs
      are small, we propose that NM cells fire in synchrony to generate large PSCs. To
      mimic the arrival of PSCs during binaural stimulation, two stimulus trains were
      summed at different delays before injection. The firing rate of NL neurons was
      greatest with zero delay. A delay of half the stimulus period evoked firing that
      was less than that evoked with a single train. Neurons lacking strong outward
      rectification exhibited neither reliable phase-locking during high-frequency
      stimulation nor sensitivity to stimulus delays. These findings suggest that the
      firing responses of NL neurons are determined primarily by their membrane
      properties.

PMID- 8558269
TI  - Leadership transition in the age of paradox.
AB  - The healthcare delivery system is undergoing great upheaval as individual
      providers respond to market pressures for aggressive cost reduction. Roles,
      relationships, processes, partnerships, and financing arrangements are on the
      table in the great race for competitive survival. The IDN department will address
      issues inherent in the evolution of free-standing acute care centers and private
      medical staffs into integrated delivery networks. It will globally explore
      alternative managed care and direct contracting at-risk strategies.

PMID- 8558270
TI  - Reducing variation in patient care. Nursing responds to capitation.
AB  - As managed care and capitation methods of payment become more common to
      hospitals, a strategy to improve quality and reduce costs is introduced in
      response to these new pressures. Nursing leaders must take the initiative and
      respond to these changes by reducing the variations in patient care. The author
      describes seven initiatives undertaken by the nursing leaders of The St. Joseph
      Healthcare System in Albuquerque. New Mexico during a 3-year period. The success
      of these initiatives and their universal application is discussed.

PMID- 8558271
TI  - Revisioning the recruitment of talented professionals.
AB  - As organizations restructure and redesign, hiring appropriate staff members
      becomes even more crucial for their success. Skill sets become more complex, fit
      becomes more significant, and fast-paced organizations do not have the time or
      resources for extensive grooming or training of in-house or newly hired
      personnel. The authors examine how talented professionals can be recruited and
      hired in a timely manner while using fewer in-house organizational resources.

PMID- 8558272
TI  - The search for the sacred. How to find new meanings in your career.

PMID- 8558273
TI  - Geriatric patients with depression. Improving outcomes using a multidisciplinary
      clinical path model.
AB  - Clinical pathways define multidisciplinary staff members' responsibilities, time
      lines, and patient outcomes. Although medical and surgical care settings
      frequently use them to improve quality, clinical, and fiscal outcomes for
      specific patient populations, staff members of psychiatric care settings have
      been hesitant to use clinical pathways because psychiatry emphasizes patient
      individuality. The authors describe the development and implementation of a
      psychiatric clinical pathway for geriatric patients with depression and identify
      common multidisciplinary interventions and a pattern of outcomes over the course
      of treatment for these patients. They also delineate quality and fiscal outcomes
      and future directions. Implementation of the pathway has been successful, and the
      development and implementation processes have applicability to other patient
      populations and care settings.

PMID- 8558275
TI  - The seven basic rules for successful redesign.
AB  - With all the hype generated by the many efforts to redesign healthcare services,
      some of the basic elements of effective change are forgotten. In their
      enthusiasm, leaders can forget those processes and tenets that can assure
      meaningful and sustainable outcomes. The author focuses on those basic rules
      that, when properly applied, can assure long-term success when undergoing change.

PMID- 8558274
TI  - Policy issues for improving institutional response to domestic violence.
AB  - The call by healthcare providers and advocates to do more for battered women in
      healthcare settings has placed nursing administrators on the front lines in
      developing protocols to identify and intervene with survivors of domestic
      violence. Institutional support and planning are essential in developing
      effective policies and protocols. The author addresses key issues for nurse
      administrators to consider when developing domestic violence policies and
      protocols.

PMID- 8558276
TI  - Democratic administration. 1954.

PMID- 8558277
TI  - The job that didn't fit. The case of Lynda.

PMID- 8558278
TI  - Educating for the community.

PMID- 8558279
TI  - Bridge to the future: nontraditional clinical settings, concepts and issues.
AB  - Healthcare restructuring in the wake of healthcare reform places greater emphasis
      on primary healthcare. Clinical education in acute care settings and existing
      community health agencies are not compatible with teaching basic concepts,
      principles and skills fundamental to nursing. Problems of clients in acute care
      settings are too complex and clients in the community are often too dispersed for
      necessary faculty support and supervision of beginning nursing students.
      Nontraditional learning settings offer the baccalaureate student the opportunity
      to practice fundamental skills of care and address professional skills of
      negotiation, assertiveness, organization, collaboration and leadership. An
      overview of faculty designed clinical learning experiences in nontraditional
      sites such as McDonald's restaurants, inner city churches, YWCA's, the campus
      community and homes are presented. The legal, ethical and academic issues
      associated with nontraditional learning settings are discussed in relation to
      individual empowerment, decision making and evaluation. Implications for the
      future address the role of the students and faculty as they interact with the
      community in which they live and practice.

PMID- 8558280
TI  - Primary health care nursing education in Canadian university schools of nursing.
AB  - This study was designed to investigate the integration of primary healthcare
      (PHC) in the curricula of Canadian university schools of nursing. A descriptive
      survey approach design was used. Development of an instrument that was tested for
      reliability and validity was followed by the survey of the 32 university schools
      of nursing in Canada that offered nursing programs in 1992-1993. Data were
      obtained from 31 of the 32 schools; representing a total of 50 programs (42
      undergraduate and 8 masters). Scales were constructed for 11 measures of PHC
      integration into the curricula. This study reveals that schools are moving toward
      integrating PHC and that approximately 60% of them can be said to have a
      reasonable degree of integration. The findings provide direction for curriculum
      development, nursing practice, and nursing research.

PMID- 8558281
TI  - Intensive immersion of nursing students in rural interdisciplinary care.
AB  - The goal of the Rural Interdisciplinary Practicum is to develop culturally
      sensitive health professionals who can function within an interdisciplinary team
      to deliver care in rural settings. Nursing and other health professions students
      enroll in a 4-semester-hour elective which is offered in an intensive 5-week, 5
      days per week block in the summer. Working closely with preceptors and faculty,
      students are immersed in a rural community. They gain expertise in their own
      specialties, collaborate in an interdisciplinary team approach to community-based
      care, and gain experience with culturally and geographically diverse groups. By
      actually living and practicing in a rural community, students learn that rural
      healthcare presents unique challenges as well as opportunities for a positive,
      high quality lifestyle, both personally and professionally. Findings to date
      indicate that the practicum positively influences students' attitudes toward
      rural, interdisciplinary practice.

PMID- 8558282
TI  - Community-focused experiences in the ADN curriculum.

PMID- 8558283
TI  - Student home care program: a real taste of home.

PMID- 8558284
TI  - The use of a homeless shelter as a clinical rotation for nursing students.
AB  - Homeless persons are a population at risk in the community with health problems
      which nursing can impact. They are a heterogeneous group from all levels of
      society with a variety of acute and chronic health problems. Senior nursing
      students learn the theories and causative factors of becoming homeless as well as
      the resources available to them in this southeastern city. The students are also
      introduced to the mechanisms by which homeless persons interact with the present
      healthcare system. The clinical experience is described as it occurs in this
      inner city location. Learning activities include health assessments, treatments,
      education, and referrals. The value of this experience to the student is that it
      promotes independence, self-direction, and priority setting. The advantages and
      disadvantages of this clinical experience for senior nursing students and their
      clients are discussed.

PMID- 8558285
TI  - Teaching population-focused practice to baccalaureate nursing students: a
      clinical model.
AB  - As the future of healthcare changes, there will be an increased demand for
      community-focused care, especially in the areas of health promotion and disease
      prevention. However, to meet these future demands, nurses must develop a
      population-focused, wellness-oriented approach to practice. This article briefly
      describes why many nurses may lack this focus, and then presents a model for
      teaching these essential community health principles to baccalaureate nursing
      students. The model uses a secondary school as the setting for the community
      health clinical experience.

PMID- 8558286
TI  - Community-based research: a tool for community empowerment and student learning.
AB  - Teaching Nursing Research is most often done close to the end of the student's
      educational experience. This article describes Northeastern University College of
      Nursing's experience using community-based research projects as a method of
      teaching nursing concepts and skills to beginning nursing students. By using
      Paulo Freire's model of Community Empowerment, a group of inner-city teens
      developed a drug awareness manual that is used to teach elementary school
      students about drugs and drug use. Through this model, students also learn that
      healthcare is a partnership among individuals, communities and professionals.

PMID- 8558287
TI  - Community program planning: a clinical outcome.
AB  - Healthcare reform has affected all aspects of the healthcare system including
      nursing education. According to Nursing's Agenda for Health Care Reform, a major
      focus of future care will be in the community. Critical thinking skills are
      needed to practice effectively in this domain. Critical thinking has been
      identified by the NLN as an outcome criteria for baccalaureate education. The
      following community health project was designed to develop this outcome skill of
      critical thinking.

PMID- 8558288
TI  - The role of empowerment in neighborhood-based nursing education.
AB  - It is a challenge to prepare nursing students for practice in the rapidly
      changing healthcare arena. A longitudinal clinical education experience, external
      to tertiary institutions and supportive of lifelong learning, creative and
      critical thinking is one way to empower students to provide appropriate care
      within a diverse population and evolving healthcare system. Nursing faculty,
      nursing students, community providers and neighborhood residents participate as
      colleagues in a joint venture of assessment, intervention, and learning.

PMID- 8558289
TI  - Low birth weight reduces the likelihood of breast-feeding among Filipino infants.
AB  - We studied the relationship of low birth weight (LBW) to concordance of mother's
      feeding intentions during pregnancy with actual feeding practices; initiation of
      breast-feeding; and patterns of feeding in the first 6 mo. Data came from the
      Cebu Longitudinal Health and Nutrition Survey, which followed 3080 mother-infant
      pairs from urban and rural communities of Metro Cebu, Philippines. We used
      logistic regression to estimate the effects of LBW on feeding practices,
      controlling for place of delivery (home, public or private health facility),
      receipt of free infant formula samples; infant sex, urban residence; primiparity,
      education level and age of the mother; and family income and assets. Birth of a
      LBW infant significantly decreased the likelihood that women would initiate
      breast-feeding. Of particular note is the finding of this decreased likelihood
      among women who during pregnancy had stated an intention to breast-feed. In a
      comparison of 6-mo feeding patterns, we also found that LBW increased the
      likelihood of not breast-feeding or of weaning before 6 mo. Among breast-feeding
      mothers, LBW increased the likelihood of full breast-feeding for 6 mo compared
      with patterns characterized by earlier supplementation with other foods and
      liquids. The negative relationship of LBW to breast-feeding was strongest when
      births took place in private or public health facilities. Given the known health
      risks of LBW and the proven benefits of breast-feeding, these results emphasize
      the need for special efforts to promote breast-feeding of LBW infants born in
      clinical settings.

PMID- 8558290
TI  - Validity of single-weight measurements to predict current malnutrition and
      mortality in children.
AB  - In this cross-sectional study of a random cluster sample of 4238 rural Zairian
      children aged 0-5 y, we assessed underweight and wasting, defined as weight-for
      age < 75%, and weight-for-height < 80% of the U.S. National Center for Health
      Statistics reference median, respectively. We determined the diagnostic validity
      of underweight and wasting for protein-energy malnutrition, taking a low arm
      circumference and clinical signs of muscle loss as criteria. Both underweight and
      wasting had low sensitivity in recognizing low arm circumference, any clinical
      muscle loss and even severe marasmus, especially in the weaning period of 12-30
      mos. Receiver operating characteristic (ROC) analysis showed that the diagnostic
      validity of weight-for-height can be improved by using a cutoff for wasting at Z
      score -0.75 instead of Z-score -2 or 80% of reference median. ROC analysis of 30
      mo mortality revealed a poor prognostic validity of weight-for-height and weight
      for-age and better performances of arm circumference (cm) and of age. These data
      suggest that nutritional intervention programs targeted at wasted or underweight
      children can have only a limited effect on the prevalence of protein-energy
      malnutrition in the community or on the long-term mortality associated with it.

PMID- 8558291
TI  - Plasma ascorbic acid concentrations are related to cardiovascular risk factors in
      African-Americans.
AB  - This study was undertaken to examine relationships among blood pressure, blood
      lipids, and plasma concentrations of ascorbic acid and malondialdehyde (MDA)
      equivalents (indicative of lipid peroxidation) in adult African-Americans.
      Subjects (n = 172, mean age = 48.0 y) were recruited from among the memberships
      of several Seventh-Day Adventist Churches. Plasma ascorbic acid and MDA
      equivalents were inversely correlated (r = -0.44, P < 0.0001). There were
      significant inverse correlations between plasma ascorbic acid levels and both
      systolic (r = -0.39, P < 0.0001) and diastolic blood pressure (r = -0.25, P <
      0.03), and between plasma ascorbic acid and serum total cholesterol (r = -0.25, P
      < 0.03), LDL-cholesterol (LDL-C) (r = -0.33, P < 0.004), and the ratio of LDL
      cholesterol to HDL-cholesterol (LDL-C/HDL-C) (r = -0.32, P < 0.004). Serum HDL
      cholesterol was positively related to plasma ascorbic acid (r = 0.22, P < 0.05).
      The correlations for MDA equivalents and the blood pressure and blood lipid
      variables were of similar magnitude to those of plasma ascorbic acid, but were in
      the opposite direction. Multiple regression analysis revealed ascorbic acid to be
      a significant independent contributor to the prediction of blood pressure and LDL
      C concentration. These data suggest that plasma concentrations of ascorbic acid
      and MDA equivalents are related to several cardiovascular risk indicators in
      black Americans.

PMID- 8558292
TI  - Human serum carotenoid concentrations are related to physiologic and lifestyle
      factors.
AB  - We examined the concentrations of five carotenoids in the serum and diet of a
      population-based sample of 400 individuals to determine what physiologic and
      lifestyle factors were related to serum carotenoid concentrations, how these
      relationships differed among the carotenoids, and if these relationships
      reflected differences in carotenoid intake. Lower serum concentrations of alpha
      carotene, beta-carotene, beta-cryptoxanthin, and lutein+zeaxanthin generally were
      associated with male gender, smoking, younger age, lower non-HDL cholesterol,
      greater ethanol consumption and higher body mass index. Serum lycopene generally
      was not related to these factors, but lower lycopene levels were associated with
      older age and lower non-HDL cholesterol. Only the hydrocarbon carotenoids (alpha-
      and beta-carotene and lycopene) were directly associated with HDL cholesterol.
      The associations of some factors (gender, age, smoking, and ethanol intake) with
      serum carotenoids were similar to the associations of these factors with levels
      in the diet, indicating that serum carotenoids may reflect the influence of these
      factors on carotenoid intake. Consistent with this notion, correlations between
      serum and dietary carotenoids did not differ between smokers and nonsmokers.
      Other factors (HDL and non-HDL cholesterol and body mass index) associated with
      carotenoids in the serum were not associated with carotenoid intake, indicating
      that physiologic conditions that affect the absorption, storage, and utilization
      of carotenoids may influence these associations. These physiologic and behavioral
      correlates of carotenoids could explain or modify associations of carotenoids
      with chronic diseases.

PMID- 8558293
TI  - Plant wax components: a new approach to estimating intake and diet composition in
      herbivores.
AB  - The nutrient status of the herbivore depends on the nutritive value of the plants
      available, the botanical composition of the consumed diet and the intake of the
      animal. It has always been difficult to quantify these last two. At present,
      intake is usually calculated from separate estimates of fecal output and diet
      digestibility. In this review we discuss the errors inherent in this approach,
      especially those associated with the determination and application of
      digestibility in vitro. We then critically evaluate a new approach to the
      estimation of intake, based on the use of plant cuticular wax alkanes as markers.
      Plant alkanes are predominantly odd-chain and substantially indigestible. They
      can be used, in combination with orally dosed even-chain alkanes, to obtain an
      intake estimate which is essentially independent of marker recovery in feces and
      which is more truly "individual" because it accommodates the level of
      digestibility occurring in individual animals. We present published data which
      indicate that the method is accurate and can be extended to measure diet
      composition as well. Previous approaches to estimating diet composition have been
      based on the laborious microscopic examination of esophageal extrusa, stomach
      contents or feces. However, most plant species have a characteristic pattern of
      alkane concentrations in their cuticular wax. This permits the estimation of diet
      composition from the pattern of alkanes in the feces and in the plants available.
      We present data to show that this approach can provide accurate estimates of diet
      composition in terms of either plant species or plant parts. A major advantage of
      the approach is that, if the animals are also dosed with even-chain alkanes,
      estimates of total intake and diet composition can be obtained simultaneously.
      The method is equally applicable to domestic and wild herbivores and to animals
      receiving supplementary feeds. In future work, the method will be extended to the
      simultaneous estimation of plant species and plant parts in the diet, and to the
      use of other wax components as markers.

PMID- 8558294
TI  - Selenoprotein P concentration in plasma is an index of selenium status in
      selenium-deficient and selenium-supplemented Chinese subjects.
AB  - Selenoprotein P, a selenium-rich plasma protein, is an index of selenium status
      in rats. Antibodies against human selenoprotein P were raised to study the
      protein and to develop a radioimmunoassay for it. A single collection of plasma
      from a healthy person in the United States contained 1.84 mumol selenium/L and
      was defined as containing 1 Unit (U) selenoprotein P/L. Removal of selenoprotein
      P from the reference plasma by an antibody column indicated that 0.81 mumol
      selenium/L, or 44% of the plasma selenium, was present as selenoprotein P. Work
      by others had determined that glutathione peroxidase accounted for 12% of plasma
      selenium. Stored plasma samples from selenium-deficient (Dechang County) and
      selenium-supplemented (Mianning County) populations in China were assayed for
      selenoprotein P. Boys aged 8-12 y had selenoprotein P concentrations of 0.10 +/-
      0.04 U/L (n = 22) in Dechang and 0.39 +/- 0.17 U/L (n = 17) in Mianning.
      Supplementation with 100 micrograms selenium as selenate per day for 14 d raised
      those levels to 0.51 +/- 0.13 U/L in Dechang and to 0.76 +/- 0.27 U/L in
      Mianning. Similar results were obtained in men, and plasma selenium
      concentrations correlated with selenoprotein P concentrations. A study comparing
      indices of selenium status was conducted in the two counties. Selenoprotein P
      concentration in Dechang subjects (n = 79) was 36% of that in Mianning subjects
      (n = 117). For plasma glutathione peroxidase activity the value was 54%; for
      plasma selenium, 47%; and for whole blood selenium, 64%. We conclude that
      selenoprotein P is the major selenoprotein in human plasma and that its
      concentration is an index of selenium nutritional status that appears to be as
      sensitive as other indices in common use.

PMID- 8558295
TI  - Maternal underweight status and inadequate rate of weight gain during the third
      trimester of pregnancy increases the risk of preterm delivery.
AB  - This study examines the differences in the pattern of weight gain according to
      trimesters of pregnancy for women who delivered term vs. preterm and analyzes the
      independent effect of prepregnancy weight status and rate of weight gain on
      delivering preterm. The differential effects of these variables on the
      etiological pathways of prematurity (preterm labor and preterm rupture of the
      amniotic membranes) were also examined. Data were collected prospectively from
      7589 pregnant women receiving care in public health clinics in the West Los
      Angeles area. Eighty percent of women identified themselves as being of Hispanic
      origin. Multivariate logistic regression techniques were used to isolate the role
      of each nutritional variable from other factors that may influence birth outcome.
      Women who delivered preterm had patterns of weight gain similar to women
      delivering term infants. Underweight status (body mass index < 19.8 kg/m2) before
      pregnancy nearly doubled the likelihood of delivering preterm [adjusted odds
      ratio (AOR) 1.98, 95% confidence interval (CI) = 1.33, 2.98). Inadequate weight
      gain in the third trimester defined as < 0.34, 0.35, 0.30 and 0.30 kg/wk for
      underweight, normal weight, overweight and obese women, respectively, increased
      the risk by a similar magnitude (AOR 1.91, 95% CI = 1.40, 2.61). Slight
      differentiation of these risk factors occurred when analyzing the etiological
      pathways of preterm birth. Preconceptional nutrition counseling and promotion of
      adequate weight gain during the third trimester of pregnancy should be components
      of public health programs designed to decrease the prevalence of preterm birth.

PMID- 8558296
TI  - Purified ferritin and soybean meal can be sources of iron for treating iron
      deficiency in rats.
AB  - Ferritin and soybean meal were reevaluated as dietary treatments of iron
      deficiency in rats. Isotopes that had been used in the past were avoided because
      of contemporary knowledge of the physiological and structural complexity of
      ferritin protein and the solid iron mineral. Rats made anemic by iron-deficient
      diets were given equivalent amounts of iron as FeSO4, horse spleen ferritin,
      baked soybean meal, or soybean meal plus ferritin. Full recovery (89-109%) from
      anemia and increased tissue iron occurred after 28 d of treatment with any of the
      iron sources, which contrasts to past bioavailability studies using 59Fe-labeled
      ferritin and generally shorter periods of observation. Cultivar-specific
      variability was observed in soybean seed soluble iron and ferritin content (1.9
      2.0 times the control cultivar, Arksoy), which was apparently heritable. The
      combined data suggest that manipulating ferritin expression and other soluble
      components of seed iron in soybeans and possibly other seeds, using Mendelian and
      biotechnological approaches, could contribute to a sustainable solution to global
      problems of iron deficiency.

PMID- 8558297
TI  - Dietary soybean protein prevents bone loss in an ovariectomized rat model of
      osteoporosis.
AB  - The purpose of this study was to examine whether soybean protein isolate prevents
      bone loss induced by ovarian hormone deficiency. Thirty-two 95-d-old Sprague
      Dawley rats were randomly assigned to four treatment groups [sham-operated
      (sham); ovariectomized (ovx); ovx+soybean; ovx + 17 beta-estradiol (E2)] and
      killed after 30 d. Rats in the sham, ovx and ovx + 17 beta-estradiol groups were
      fed a casein-based diet, and the soybean group was fed soybean protein isolate
      instead of casein; the diets were otherwise comparable. Rats in the ovx group had
      significantly lower densities of the right femur (P < 0.001) and the fourth
      lumbar vertebra (P < 0.05) than rats in the sham group. These lower bone
      densities were not observed in animals receiving 17 beta-estradiol or fed
      soybean. The ovx group also had significantly (P < 0.01) greater serum
      concentrations of 1,25-dihydroxycholecalciferol than the other three groups. Our
      findings suggest that dietary soybean protein is effective in preventing bone
      loss due to ovarian hormone deficiency. Because serum activities of both alkaline
      phosphatase and tartrate-resistant acid phosphatase were significantly greater in
      the ovx group and in the ovx + soybean group but not in the group receiving 17
      beta-estradiol, compared with sham animals, this confirms that ovariectomy
      enhances and 17 beta-estradiol suppresses the rate of bone turnover. Despite the
      higher rate of bone turnover in the soybean-fed animals, the vertebral and
      femoral bone densities of these rats were significantly greater than those of
      rats in the ovx group, suggesting that formation exceeded resorption. Further
      studies are needed to clarify whether this protective effect on bone is due to
      the protein itself or to the presence of isoflavones in soybean protein.

PMID- 8558298
TI  - Growth failure and altered body composition are established by one month of age
      in infants with bronchopulmonary dysplasia.
AB  - Long-term growth failure and altered body composition are common consequences of
      bronchopulmonary dysplasia (BPD). We hypothesized that these chronic findings are
      preceded by uncompensated, acute early growth failure. The purpose of this study
      was to evaluate the effects of developing bronchopulmonary dysplasia on body
      composition and growth of very-low-birth-weight (VLBW) infants during the first
      six postnatal weeks. Arm muscle and fat accretion and changes in weight, length
      and head circumference were evaluated in 16 very-low-birth-weight infants who
      developed bronchopulmonary dysplasia and compared with 16 birth-weight-matched
      control infants without bronchopulmonary dysplasia. During the 1st wk, both
      groups experienced similarly low nutritional intakes, wasting of arm muscle and
      fat stores, and reduced weight, length and head circumference growth velocities,
      compared with intrauterine growth standards. Between wk 2 and 4, infants with
      developing bronchopulmonary dysplasia consumed less protein and energy (P <
      0.05), accreted less arm fat and muscle (P < 0.05), and grew more slowly than
      control infants in all measured variables (P < 0.05). When infants with
      bronchopulmonary dysplasia had achieved full enteral feedings and had similar
      protein-energy intakes to control infants, they demonstrated similar rates of
      growth and arm muscle and fat accretion, but did not demonstrate catch-up growth.
      These data support the speculation that early reductions in muscle and fat
      accretion and growth velocity contribute to the long-term growth failure in
      infants with bronchopulmonary dysplasia. Prevention may require greater attention
      to defining and delivering optimal nutritional therapy to physiologically
      unstable premature infants in the immediate postnatal period.

PMID- 8558299
TI  - Absorption and excretion of the soy isoflavone genistein in rats.
AB  - Rodent models have been used to study the anticarcinogenic properties of the soy
      isoflavones, particularly genistein, but there is little information regarding
      the pharmacokinetics of the absorption and excretion of genistein. In this study,
      rats were given a single oral dose of genistein (20 mg/kg body weight) or an
      equivalent dose of its glycone forms, as an isoflavone-rich soy extract.
      Concentrations of genistein were measured in plasma, urine and feces at intervals
      up to 48 h after dosing. Plasma genistein concentration at 2 h after dosing was
      11.0 +/- 2.3 mumol/L in genistein-treated rats compared with 4.93 +/- 0.22
      mumol/L (P = 0.025) in soy extract-treated rats, but there were no significant
      differences at 8 h and later times. The mean urinary excretion rate during the
      first 2 h after dosing was more than 10 times higher in the genistein group
      compared with the soy extract group (0.27 +/- 0.08 mumol/h and 0.020 +/- 0.011
      mumol/h, respectively, P = 0.017) but the percentage of dose recovered in urine
      over 48 h was not different between groups (19.9 +/- 2.4% genistein treated; 17.5
      +/- 1.1% soy extract treated). There were no significant differences between
      groups in the recovery of genistein in feces (21.9 +/- 2.8% and 21.1 +/- 2.5% of
      dose, respectively). Only 6.1 +/- 0.9% of the daidzein from the soy extract was
      recovered in the feces. The results suggest that the extent of absorption of
      genistein is similar for the glycone and aglycone forms. Although higher initial
      plasma concentrations may be achieved with the aglycone, similar long-term
      concentrations exist for both forms of isoflavone.

PMID- 8558300
TI  - Iron and copper interact during their uptake and deposition in the brain and
      other organs of developing rats exposed to dietary excess of the two metals.
AB  - This study examined the effect of iron and copper loading on rat brain, liver,
      kidney, femur, blood and plasma concentrations of these metals and iron transport
      into the organs during development. Dams were fed control diets or iron-loaded
      diets (20 g/kg carbonyl iron) with either distilled water or copper-loaded water
      (350 mg/L) beginning at d 20 of pregnancy. The weanlings also had access to the
      diets and water supply and were examined at 15, 21 and 63 d of age. The iron
      content of the liver was 17- to 30-fold greater in iron-loaded rats than in
      controls, whereas liver, kidney and plasma copper levels generally were lower.
      Iron loading alone did not increase brain iron concentrations, suggesting the
      blood-brain barrier is already developed at birth. However, dual loading of iron
      and copper resulted in elevated concentrations of brain non-heme iron and copper
      in 15- and 63-d-old rats compared with animals loaded with iron alone. These
      results suggest that brain iron uptake mechanisms may be different when excess
      copper is present. Liver non-heme iron was also greater in copper-loaded rats,
      irrespective of iron status. However, kidney iron concentrations generally were
      not affected by dietary copper. In rats fed the copper-containing diet, the
      uptake of iron into brain and liver was significantly lower than in those fed the
      control diet, suggesting that copper loading can decrease iron uptake into
      organs. It is concluded that combined dietary supplementation with iron and
      copper can alter the metabolism of each metal. These changes are age and organ
      dependent. Developing rats may be very susceptible to these combined overload
      states because significant effects are seen in early adulthood.

PMID- 8558301
TI  - Maillard reaction products in purified diets induce taurine depletion in cats
      which is reversed by antibiotics.
AB  - The effects of heat processing (Maillard reaction) and addition of antibiotics to
      diets on the metabolism of taurine in adult cats were studied. Groups of four
      cats were given daily 22 g/kg body weight one of four purified diets based on
      casein and starch. All diets contained the same major ingredients as the control
      (diet 1), except for starch substitutions. Diet 2 was autoclaved; in diet 3, 50 g
      glucose replaced 50 g starch before autoclaving; in diet 4, only the casein
      component was autoclaved with 50 g glucose before addition to the diet. Diets
      were fed for 5 wk, then a mixture of antibiotics was added to all diets and they
      were fed for a further 5 wk. In the first (no antibiotics) period, cats given the
      Maillard reaction products (diets 3 and 4) had a significant depletion of plasma
      and whole blood taurine and had twice the fecal, but less than half the urinary
      total taurine excretion of control cats. The addition of antibiotics to the diets
      restored plasma and whole blood concentration in cats given diets 3 and 4,
      reduced fecal and increased urinary taurine excretion, and decreased fecal
      cholyltaurine hydrolase activity. These results suggest that Maillard reaction
      products promote an enteric flora that favors degradation of taurine and
      decreases recycling of taurine by the enterohepatic route.

PMID- 8558302
TI  - Dietary beta-carotene elevates plasma steady-state and tissue concentrations of
      beta-carotene and enhances vitamin A balance in preruminant calves.
AB  - Preruminant calves are regarded as a model for studying beta-carotene
      bioavailability in humans. The objectives of this trial were to determine the
      relationship between multiple beta-carotene doses and plasma steady-state
      concentration, accumulation in selected tissues, and vitamin A balance in liver.
      Seventy newborn Holstein calves in six treatments (n = 10/treatment) were fed a
      complete milk replacer diet low in vitamin A and supplemented with beta-carotene
      doses of 0, 0.23, 0.46, 0.92, 1.84 or 3.68 mumol/(kg body wt.d) for 28 d. Ten
      calves were killed on d 1. Plasma beta-carotene increased in relation to log
      transformations of dose and time (P < 0.05) in all supplemented calves and steady
      state was attained after 4 wk. For doses up to 0.92 mumol/(kg body wt.d), the
      dose-response relationship was linear. A dose-dependent accumulation of beta
      carotene was found for liver, heart, lungs, adrenals and adipose tissue. All
      trans-beta-carotene was the only isomer in plasma and adrenals and the
      predominant isomer in the remaining tissues. In liver, vitamin A increased with
      beta-carotene uptake. Hepatic balance between vitamin A accumulation and loss was
      achieved at beta-carotene intake of 0.36 mumol/(kg body wt.d) for a calf of 45
      kg. It is concluded that preruminant calves within 1 mo of age utilize beta
      carotene as a source of vitamin A, and that for testing bioavailability of beta
      carotene sources, doses up to 0.92 mumol beta-carotene/(kg body wt.d) are most
      appropriate.

PMID- 8558303
TI  - Interactions between ruminal degradable nitrogen intake and in vitro addition of
      substrates on patterns of amino acid metabolism in isolated ovine hepatocytes.
AB  - The effects of ammonia (as NH4Cl) and propionate on the partitioning of amino
      acids between oxidation and gluconeogenesis were determined in isolated
      hepatocytes obtained from sheep fed a basal diet (50:50 bromegrass hay:corn;
      asfed basis) with or without urea. Hepatocyte suspensions were incubated with
      NH4Cl (0, 1.25, 2.5 and 5.0 mmol/L) and/or propionate (0, 2.5 and 5.0 mmol/L), in
      the presence of either 2.5 mmol/L L-alanine and 18.5 kBq L-[1-14C]alanine or 2.5
      mmol/L L-glutamate and 18.5 kBq L-[1-14C]glutamate. Increasing the level of
      ruminal degradable nitrogen with urea increased in vitro rates of oxidation to
      14CO2 of [1-14C]alanine, but not [1-14C]glutamate. Increasing in vitro
      concentrations of NH4Cl and propionate between 0 and 5 mmol/L reduced the rates
      of oxidation to 14CO2 of both [1-14C]alanine and [1-14C]glutamate. Synthesis of
      [14C]glucose with [1-14C]alanine, but not [1-14C]glutamate as the substrate, was
      increased 100% by feeding urea. Increasing in vitro levels of NH4Cl between 0 and
      5 mmol/L reduced the rates of conversion of [1-14C]alanine and [1-14C]glutamate
      to [14C]glucose in hepatocytes isolated from sheep fed both diets. Increasing in
      vitro levels of propionate between 0 and 2.5 mmol/L elevated production rates of
      [14C]glucose from both radiotracers, but from 2.5 to 5.0 mmol/L propionate no
      further increase was evident. Feeding urea increased in vitro rates of urea
      nitrogen production. Increasing propionate levels between 0 and 5 mmol/L reduced
      ureagenic rates in liver cells isolated from sheep fed both diets. Oxygen (O2)
      uptake was unaffected by diet and NH4Cl; however, increasing propionate between 0
      and 5 mmol/L increased rates of O2 uptake. It is concluded that in isolated sheep
      hepatocytes, detoxification of excessive ammonia may cause a repartitioning of
      alanine and glutamate metabolism towards oxidation and gluconeogenesis.

PMID- 8558304
TI  - The acrodermatitis enteropathica mutation transiently affects zinc metabolism in
      human fibroblasts.
AB  - The acrodermatitis enteropathica (AE) mutation has been shown to affect zinc
      transport in human intestinal biopsies. However, whether the mutation is also
      expressed in human fibroblasts has not been determined. The activity of the zinc
      dependent enzyme, 5' nucleotidase, and cell zinc content were measured in normal
      and AE fibroblasts 2 and 4 d after subculturing to determine the effect of the AE
      mutation on zinc metabolism. The activity of 5' nucleotidase in AE cells was 68%
      of normal at 2 d after subculturing. Although 5' nucleotidase activity had
      decreased significantly in both normal and AE fibroblasts at 4 d after
      subculturing, there was no significant difference between the two genotypes. The
      zinc content of AE fibroblasts was also significantly reduced. Acrodermatitis
      enteropathica fibroblasts contained 62% less zinc than normal fibroblasts at 2 d.
      By 4 d the normal fibroblast zinc content had decreased to that of the AE
      fibroblasts. The uptake and transport of 65Zn into AE fibroblasts at 2 d was
      measured because these cells exhibited reduced 5' nucleotidase activity and cell
      zinc content at this time. The uptake of zinc over a 90-min time period was the
      same in the two genotypes. However, AE fibroblasts incubated with 2-10 mumol Zn/L
      for 15 min had significantly slower zinc transport compared with normal
      fibroblasts. In both genotypes, Michaelis-Menten kinetics were observed. Normal
      and AE fibroblasts had similar affinities for zinc (Km), but AE fibroblasts
      exhibited a Vmax which was reduced by 38%. These results indicate that the
      phenotypic expression of the AE mutation occurs in a time-dependent manner, is
      not restricted to the intestine and is also transiently expressed in human
      fibroblasts, resulting in abnormal zinc metabolism in these cells.

PMID- 8558305
TI  - Absorption and metabolism of lipids in rats depend on fatty acid isomeric
      position.
AB  - This study determined the effect of dietary (dipalmitoyl) triacylglycerol (TAG)
      structure on the absorption and metabolism of fat in the presence or absence of
      cholesterol. Sprague-Dawley male rats weighing approximately 180 g were fed diets
      containing 10 g/100 g diet 1,3-dipalmitoyl-2-oleoyl-glycerol-rich oil (POP) or
      1(3),2-dipalmitoyl-3(1)-oleoyl-glycerol-rich oil (PPO), either with or without
      cholesterol supplementation (0.5 g/100 g diet), for 2 wk. There were no
      differences in the growth of rats fed the various diets. The apparent absorption
      efficiency of dietary fat especially the apparent absorption efficiency of
      palmitic acid, was significantly lower in the POP groups than in the groups fed
      the PPO diets. The excretion of cholesterol in feces of rats fed the POP diet
      with cholesterol was significantly greater than those fed the PPO diet containing
      cholesterol. The excretion of total bile acids in the rats fed cholesterol was
      significantly greater than in those fed the diets without cholesterol. Liver
      cholesterol was significantly greater in rats fed cholesterol and was not
      affected by the TAG structure. Plasma cholesterol was significantly lower in the
      POP dietary groups than in the PPO groups. These results suggest that the
      absorption and metabolism of fat depend on the positional isomer of the fatty
      acid.

PMID- 8558306
TI  - Methionine-containing peptides can be used as methionine sources for protein
      accretion in cultured C2C12 and MAC-T cells.
AB  - Twenty-two methionine-containing di- to octapeptides were evaluated for their
      ability to be a source of methionine to support protein accretion in C2C12
      myogenic and MAC-T bovine mammary epithelial cells. The cell cultures were
      incubated for 72 h at 37 degrees C in a humidified environment of 90% air: 10%
      CO2 for C2C12 cells or 95% air: 5% CO2 for MAC-T cells. The basal medium
      contained methionine-free Dulbecco's modified Eagle's medium and 6% desalted
      fetal bovine serum. Treatments included basal medium, the basal medium
      supplemented with one of the 22 methionine-containing peptides, or the basal
      medium supplemented with free L-methionine. Methionine-containing peptides with
      the exception of glycylmethionine and prolylmethionine in C2C12 cells were able
      to support protein accretion with responses ranging from 29.1 to 123.3% of the
      response of L-methionine. Dipeptides with methionine at the N-terminus promoted
      greater (P < 0.0001) protein accretion than dipeptides with methionine at the C
      terminus. Stimulation of protein accretion by seven pairs of dipeptides with
      methionine at either the C- or the N-terminus was linearly (P < 0.0001) related
      to the hydrophobicity of the dipeptides. These results indicate that C2C12
      myogenic and MAC-T mammary epithelial cells have the ability to utilize
      methionine-containing peptides as sources of methionine to support protein
      accretion.

PMID- 8558307
TI  - Folate transport pathways regulate urinary excretion of 5-methyltetrahydrofolate
      in isolated perfused rat kidney.
AB  - The reabsorption of 5-methyltetrahydrofolic acid (5-CH3-H4PteGlu) by the renal
      proximal tubule has an important role in the maintenance of plasma folate
      concentrations. However, the mechanism by which this vitamin traverses the renal
      epithelium remains to be determined. Studies in cultured cells have suggested
      that the folate receptor in association with a probenecid-sensitive anion carrier
      may be involved in the transmembrane transport of the vitamin. Because 5-CH3
      H4PteGlu is reabsorbed and metabolized in the isolated perfused rat kidney (IPRK)
      in a smaller manner to in vivo models, the IPRK was used to evaluate pathways
      involved in folate reabsorption. Reabsorption of 5-CH3-H4PteGlu could not be
      saturated in the isolated perfused rat kidney, even at concentrations up to 2
      mumol/L. Folic acid (PteGlu) was used as a competitive inhibitor of FR-dependent
      reabsorption of 5-CH3-H4PteGlu. When 5-CH3-H4PteGlu was maintained at 1 nmol/L (a
      concentration at which receptor-mediated transport should be maximal), PteGlu (up
      to 100 nmol/L) had no effect on reabsorption. The addition of probenecid (1
      mmol/L) did not affect the reabsorption of 5-CH3-H4PteGlu but inhibited the
      fractional excretion of the anion para-aminohippurate. Probenecid also inhibited
      the urinary excretion of 5-CH3-H4PteGlu metabolites, indicating that reabsorbed 5
      CH3-H4PteGlu was metabolized to products that were subsequently secreted into the
      urine by anion exchange pathways. The physiological importance of a folate
      receptor-mediated reabsorption of 5-CH3-H4PteGlu appears to be minor in the
      isolated perfused rat kidney, whereas nonspecific pathways appear to play a major
      role in the renal folate reabsorption.

PMID- 8558308
TI  - The Caco-2 cell culture system can be used as a model to study food iron
      availability.
AB  - To assess the usefulness of the Caco-2 cell culture system as a model to study
      the availability of dietary iron, preliminary experiments were performed to
      determine the optimal conditions for iron uptake and transport. Iron uptake of
      radioactive ferrous sulfate was optimal at pH 5.5 using a 2:1 molar ratio of
      ascorbic acid to iron and a 1-h incubation time. Under these experimental
      conditions, we studied the effect on iron uptake of adding supernatants from
      homogenates of different meat sources, soybean protein isolates, egg albumen and
      bovine serum albumin. Iron uptake was 6.3 +/- 1.7% from meat, which was
      significantly greater (P < 0.001) than the values of 1.2 +/- 0.3% from soybean
      protein, 1.3 +/- 0.3% from egg albumen and 0.8 +/- 0.1% from bovine serum
      albumin. Iron uptake was also significantly higher from digested meat samples
      than from undigested meat when the protein concentration was equalized.
      Measurements of iron uptake and protein concentration from fractions obtained
      after preparative isoelectric focusing of meat and soybean protein extracts
      showed two peaks of higher protein concentration and iron uptake in meat,
      apparently not found in soybean protein, that contained the factor(s) responsible
      for the higher iron uptake by the cells. In view of these observed similarities
      with iron absorption studies in humans, we conclude that the Caco-2 cell culture
      system is a useful in vitro model to study food iron availability.

PMID- 8558310
TI  - A high protein diet does not improve protein synthesis in the nonweight-bearing
      rat tibialis anterior muscle.
AB  - We recently demonstrated that a high protein intake partially prevented the
      decrease in protein synthesis in the atrophied dark soleus muscle of rats that
      were hindlimb suspended (HS) for 21 d. To study the possible role of protein
      intake in a muscle more representative of the whole musculature, we measured the
      effect of a high protein (HP) (30%) and a medium protein (MP) (15%) diet on
      protein synthesis in the pale fast-twitch tibialis anterior muscle of HS rats.
      The HS animals were suspended by the tail for 21 d so that only their front legs
      were able to rest on the floor. The fractional rate of protein synthesis (Ks) was
      determined in vivo using a flooding dose method. A significantly lower Ks (24
      25%) was found in both HS-MP and HS-HP rats compared with their pair-fed control
      groups. Reduced Ks in HS-MP rats relative to their pair-fed controls resulted
      from a decrease in the translational efficiency (KRNA, 23%, P < 0.01), while the
      ratio of RNA to protein (Cs) was unaffected. In contrast, the decrease in KRNA
      was prevented in the HS-HP animals compared with their pair-fed controls (P <
      0.05). Hindlimb suspension did not alter fiber type distribution in the tibialis
      anterior muscle. However, a higher proportion of intermediate and Type I fibers
      with a concomitant decrease in Type II fibers was observed in both CT and HS
      animals fed the HP diet compared with those fed the MP diet (P < 0.05). These
      data clearly establish that depressed protein synthesis contributes to altered
      protein accretion in fast-twitch muscles during long-term hindlimb suspension.
      Although the HP diet prevented the decrease in translational efficiency in
      muscles from HS rats, it neither sustained protein synthesis nor prevented the
      reduction in muscle growth. Thus, it seems very unlikely that a high protein diet
      had any beneficial effect on the overall musculature during weightlessness in
      rats.

PMID- 8558309
TI  - Diet-induced nephrocalcinosis in female rats is irreversible and is induced
      primarily before the completion of adolescence.
AB  - The effect of altering the dietary Ca:P ratio during critical points of growth
      (based on reproductive and skeletal age) on kidney calcification in female rats
      was investigated. Groups of weanling animals were fed one of three nutritionally
      complete but calcium-altered diets (0.25, 0.5 or 1.0 g Ca/100 g diet) from 4 to
      12 wk of age (Phase 1). Phosphorus concentration remained constant at 0.4 g/100 g
      diet resulting in Ca:P molar ratios of 0.48, 0.96 and 1.92, respectively. During
      Phase 2, the same animals within each diet group were then rerandomized into one
      of the above diets and fed for an additional 25 wk. Each group contained five
      rats. The data from the nine treatment groups were analyzed statistically using a
      two-way ANOVA (Phase 1 dietary Ca level by Phase 2 dietary Ca level). The level
      of dietary Ca during Phase 1 only exerted a significant influence on kidney Ca
      accumulation. Rats fed the two lower dietary Ca levels, and hence lower dietary
      Ca:P molar ratios, during Phase 1 had two- to threefold greater kidney Ca
      concentration and kidney ash Ca concentration than rats fed the diet with the
      highest dietary Ca level (1.92 Ca:P molar ratio) during Phase 1, regardless of
      the Ca intake during Phase 2. In contrast, the dietary Ca:P molar ratio during
      Phase 2 had little effect either positively or negatively on the kidney Ca
      concentration that had been established during Phase 1. The results indicate that
      dietary-induced nephrocalcinosis in female rats is irreversible and is induced
      primarily before the completion of adolescence (approximately 12 wk of age) in
      Sprague-Dawley female rats.

PMID- 8558311
TI  - Manganese protects against heart mitochondrial lipid peroxidation in rats fed
      high levels of polyunsaturated fatty acids.
AB  - We demonstrated previously that dietary manganese (Mn) deficiency depressed Mn
      concentrations in most tissues and consistently depressed Mn superoxide dismutase
      (MnSOD) levels in heart. To examine the functional consequences of these effects,
      we fed weanling male Sprague-Dawley rats (n = 12/diet) diets containing 20%
      (wt/wt) corn oil or 19% menhaden oil + 1% corn oil by weight and 0.75 or 82 mg
      Mn/kg diet for 2 mo (the fish oil mixture was supplemented with (+)-(mixed)-alpha
      tocopherol to the level in corn oil). Heart and liver Mn concentrations in the Mn
      deficient rats were 56% of those in Mn-adequate rats (P < 0.0001), confirming Mn
      deficiency. The Mn-deficient rats had more conjugated dienes in heart
      mitochondria than Mn-adequate rats (P < 0.001); rats fed fish oil had more
      conjugated dienes than those fed corn oil (P < 0.001). The MnSOD activity was
      inversely correlated with conjugated dienes (r = -0.71, P < 0.005), and Mn
      deficient rats had 37% less MnSOD activity in the heart than did Mn-adequate rats
      (P < 0.0001). The dietary treatments did not affect heart microsomal conjugated
      diene formation, possibly because of compensation by copper-zinc (CuZn) SOD
      activity; CuZnSOD activities were 35% greater in the hearts of Mn-deficient
      animals (P < 0.01). Liver was less sensitive to Mn deficiency than was the heart
      as judged by MnSOD activity and conjugated diene formation. This work is the
      first to demonstrate that dietary Mn protects against in vivo oxidation of heart
      mitochondrial membranes.

PMID- 8558312
TI  - L-glutamine supplementation of a high fat diet reduces body weight and attenuates
      hyperglycemia and hyperinsulinemia in C57BL/6J mice.
AB  - C57BL/6J (B/6J) mice are genetically predisposed to become overweight and develop
      hyperglycemia if raised on a high fat diet. The purpose of the present study was
      to explore the effect of dietary supplementation of L-glutamine (Gln), an
      inhibitor of fatty acid oxidation, on the development of hyperglycemia and
      excessive weight gain. Groups of 10 age- and weight-matched male B/6J mice were
      raised on one of four diets: 1) a low fat, low sucrose (LL), studied separately,
      2) a high fat, low sucrose (HL) diet alone, 3) high fat, low sucrose supplemented
      with L-glutamine (HL+Gln) and 4) high fat, low sucrose supplemented with L
      alanine (HL+Ala). Energy intake, body weight, plasma glucose and insulin
      concentrations were monitored over time. We found no difference in energy intake
      per unit body weight between any groups after the first 2 wk of feeding. However,
      the mean +/- SEM for body weight (27.1 +/- 0.6 g) of the LL group measured at 16
      wk was lower (P < 0.05) than that of the HL group at 37.9 +/- 1.9 g. Also, after
      5.5 mo, the mean +/- SEM for plasma glucose and insulin concentrations in the LL
      group of mice were 6.9 +/- 0.4 mmol/l and 146 +/- 30 pmol/l, which were lower (P
      < 0.05) than those in the HL group at 10.1 +/- 0.9 mmol/l and 438 +/- 84 pmol/l,
      respectively. Although both amino acids caused a 10% reduction (P < 0.05) in body
      weight compared with HL feeding at wk 16, only Gln supplementation resulted in
      persistent reductions in both plasma glucose and insulin concentrations over 5.5
      mo. In another experiment, when Gln was added to the high fat (HL) diet of heavy
      hyperglycemic animals for 2 mo, body weight gain, hyperglycemia and
      hyperinsulinemia were attenuated. In conclusion, supplementing glutamine to a
      high fat diet reduces body weight and attenuated hyperglycemia and
      hyperinsulinemia in B/6J mice.

PMID- 8558313
TI  - Lactitol enhances short-chain fatty acid and gas production by swine cecal
      microflora to a greater extent when fermenting low rather than high fiber diets.
AB  - The study was conducted to determine if the response of swine cecal microflora to
      lactitol (beta-D-galactopyranosyl-(1-->4)-D-sorbitol; 3 mmol/L) varies when
      fermenting low (LF) or high fiber (HF) predigested diets. The inoculum was
      collected from four sows fitted with cecal cannulas, pooled, buffered and
      dispensed in 27 vessels under anaerobic conditions. The LF or HF predigested
      diets were used as substrate in two separate experiments. In each trial nine
      vessels were used as controls (C) without feed addition, nine received
      predigested feed (LF or HF) and the remaining nine vessels received the same
      amount of feed with the supplementation of lactitol (LF+L or HF+L). Lactitol (L)
      significantly lowered pH and the acetic to propionic acid ratio in the first 8 h
      of fermentation in both experiments (P < 0.05). At 4 and 8 h, the addition of
      lactitol reduced ammonia by 100 and 84% in LF+L and by 56 and 38% in HF+L (P <
      0.05). In addition, LF+L and HF+L diets gave higher short-chain fatty acid energy
      yields by 70 and 40% than LF and HF, respectively (P < 0.05). Two bacterial
      growth models (logistic and Gompertz) were tested to fit gas production data. The
      Gompertz equation provided a better fit than the logistic model to gas production
      data for both LF and HF experiments. Lactitol reduced culture lag time in both
      experiments by approximately 50%, but it increased gas production rate and
      maximum gas production by approximately 60% only when the microflora was
      fermenting the LF predigested diet (P < 0.05). No difference in the duration of
      the exponential phase due to lactitol was observed in either experiment. Our
      results indicate that lactitol may be an interesting additive to animal feeding.
      It controlled harmful fermentation processes and stimulated short-chain fatty
      acid production to a greater extent in low than in high fiber diets, suggesting
      an improved fermentation of low fiber feed carbohydrates and eventually an
      increased availability of short-chain fatty acids for the host.

PMID- 8558314
TI  - Severe protein deficiency and repletion alter body and brain composition and
      organ weights in infant pigs.
AB  - Three-wk-old genetically lean or obese pigs were used in two experiments to
      determine the changes in body composition, visceral organs and brain in response
      to severe protein deficiency. In Experiment 1, 16 obese pigs were fed an adequate
      (A, 21% protein, 3% fat) or a protein-deficient (D, 5% protein, 23% fat) diet for
      7 wk. One-half of each group was killed at 7 wk, and the remainder of each group
      was fed the A diet for an additional 8 wk. At 7 wk, pigs fed D contained a higher
      percentage of fat than those fed A (P < 0.01); after 8-wk of repletion, body
      composition of the two groups was similar. Duodenum, jejunum, and ileum of the
      protein-deficient pigs had severely atrophic villi, submucosal edema, and
      atrophic muscle layers; after 8 wk of repletion, however, microscopic
      architecture of the gastrointestinal tract was restored to normal. Absolute
      cerebrum weight at 7 wk, but not after 8 wk repletion, in the pigs fed D were
      significantly less than in pigs fed A, indicating reduced brain cellularity after
      7 wk of protein restriction, but not after 8 wk repletion. In Experiment 2,
      genetically obese (O, n = 8) and lean (L, n = 8) pigs consumed the A or D diet ad
      libitum for 10 wk. L and O pigs responded similarly to protein deficiency; D pigs
      were fatter than A pigs and plasma constituents, bone mineral content, bone
      mineral density and most organ weights revealed no interactions between diet and
      genotype. The pig model system used in these experiments enabled the isolation of
      protein deficiency from infectious disease, parasites and social environmental
      stimulation that may confound interpretation of human infant malnutrition
      experiments. The data suggest that genetically controlled body fatness is not a
      major determinant in the response of the infant pig to severe protein deficiency.

PMID- 8558315
TI  - Wheat bran abolishes the inverse relationship between calcium load size and
      absorption fraction in women.
AB  - Fractional calcium absorption from varying intakes of calcium carbonate co
      ingested with wheat bran, as well as alone, was measured in a randomized
      crossover study in healthy adult women. The calcium carbonate was intrinsically
      labeled with 45Ca. Absorption from the carbonate, ingested without bran, showed
      the expected inverse relationship to the logarithm of ingested load size (slope =
      -0.1199; not substantially different from the value previously reported for
      milk). At 0.5 mmol calcium load, fractional absorption averaged 0.769 +/- 0.134,
      whereas at 12.5 mmol load it averaged 0.378 +/- 0.069. In contrast, fractional
      absorption from calcium carbonate co-ingested with 40 g of a cereal product
      containing 16 g wheat bran, across a calcium load range from 0.5 to 15.5 mmol,
      was essentially constant (mean for all loads: 0.230 +/- 0.069). Thus, the calcium
      binding capacity of the bran cereal altered the usual inverse relationship
      between calcium load and fractional absorption. In vitro calcium binding to the
      bran cereal was linear over a wide range of calcium levels. This suggests that
      binding of calcium to one or more components of the bran cereal is sufficient to
      explain the reduced absorption demonstrated in vivo.

PMID- 8558316
TI  - Hemicellulose does not affect iron bioavailability in chicks.
AB  - Two iron repletion experiments using hemoglobin as a response criterion were
      conducted to assess effects of hemicelluloses on iron bioavailability to chicks.
      In Experiment 1, iron bioavailability from intact fiber sources was determined by
      adding tomato pomace (14.6% hemicelluloses), soybean hulls (20.6%
      hemicelluloses), beet pulp (21.5% hemicelluloses), orchard grass (24.1%
      hemicelluloses) and corn fiber (55.2% hemicelluloses) to a casein dextrose basal
      diet providing 0.4-4.1% hemicelluloses to the diet. Test foods were analyzed for
      iron, total dietary fiber, neutral detergent residue, neutral detergent fiber,
      acid detergent fiber, acid detergent lignin, pectins and uronic acids.
      Hemicelluloses were determined by the difference of neutral detergent residue
      minus acid detergent fiber. Iron bioavailability was determined by the standard
      curve method to be (percent relative to ferrous sulfate using hemoglobin as the
      response criterion) as follows: tomato pomace, 82.0; soybean hulls, 94.0; beet
      pulp, 26.5; orchard grass, 68.9; corn fiber, 69.4. Iron bioavailability was not
      related to hemicellulose content of test foods or diets. In Experiment 2, the
      effect of psyllium husk (a fiber source that contains predominantly
      hemicelluloses) on iron bioavailability from ferrous sulfate was assessed.
      Bioavailability was determined by the slope ratio method where treatments
      consisted of graded levels of ferrous sulfate in the presence and absence of 5%
      dietary psyllium. Although iron intrinsic to psyllium was unavailable,
      bioavailability of ferrous sulfate iron was not affected (P > 0.05) by the
      presence of psyllium. Thus, there was no clear effect of hemicelluloses on iron
      bioavailability. However, some feeds that contained high levels of hemicelluloses
      had low intrinsic iron bioavailabilities, suggesting that other dietary factors
      are primarily responsible for determining iron bioavailability from these feed
      components.

PMID- 8558317
TI  - Weight loss alters organ concentrations and contents of lead and some essential
      divalent metals in rats previously exposed to lead.
AB  - The loss of adipose tissue during energy restriction may be accompanied by a loss
      of lean body mass, including bone mass. Because most of the body lead burden is
      in the skeleton, we studied the effects of weight loss on the concentrations of
      lead in bone, blood and several organs in rats with prior but not current lead
      exposure. Concentrations of the essential divalent metals calcium, copper, iron,
      magnesium and zinc were also determined for comparison with lead. Lead-exposed
      rats (n = 25) were randomly assigned to one of three treatment groups: weight
      maintenance (WM), moderate weight loss (MWL) or substantial weight loss (SWL).
      For the two last-named groups, food intake was restricted for 4 wk to 70 and 40%
      of that of the WM group. Lead concentrations did not differ significantly (ANOVA,
      P > 0.05) among the three groups for blood, brain and bone. Significantly higher
      liver lead concentrations were observed in the SWL rats than in the WM and MWL
      groups. In general, organ concentrations of calcium, copper, magnesium and zinc
      were either lower or did not differ in the groups losing weight compared with the
      WM group. In contrast, organ Iron concentrations of the SWL group were higher
      than those of the other groups except in brain where there were no significant
      differences. The total liver content of lead was highest in the SWL group, but
      the lead content of other organs did not differ among the treatment groups. The
      contents of calcium, copper, magnesium and zinc generally were lower in the MWL
      and SWL groups than in the WM group in the liver and some of the other organs.
      The results demonstrate that weight loss can increase the quantity and
      concentration of lead in the liver, even in the absence of continued lead
      exposure. The data also demonstrate considerable differences among organ divalent
      metals in response to weight loss.

PMID- 8558318
TI  - Response of rainbow trout (Oncorhynchus mykiss) growing from 50 to 200 g to
      supplements of dibasic sodium phosphate in a semipurified diet.
AB  - Effects of increasing dietary concentrations of phosphorus on growth, feed
      intake, feed conversion, composition of gain and concentration of inorganic
      phosphate in plasma were studied in rainbow trout. Twelve groups of 20 trout
      initially weighing 53 +/- 0.6 g/fish were fed semipurified diets containing 19.6
      MJ digestible energy per kilogram of dry matter. Twelve levels of phosphorus
      ranging from 1.03 to 10.96 g/kg dry matter were achieved by replacing inorganic
      binder with dibasic sodium phosphate in 11 graded levels. Nonlinear responses of
      trout to increasing dietary phosphorus concentration determined over 53 d were
      described using exponential functions. Feed intake, growth rate and feed
      conversion ratio as well as plasma inorganic phosphate concentration increased
      with increasing dietary phosphorus concentration. The concentrations of
      phosphorus, calcium, magnesium and potassium in weight gain increased, whereas
      concentrations of lipids and energy in weight gain decreased with increasing
      dietary phosphorus concentration. Concentrations of protein and sodium in weight
      gain were unaffected. Different concentrations of dietary phosphorus were
      required for achieving 95% of the plateau value determined for desired traits. In
      growth rate and phosphorus deposition, the required phosphorus concentrations
      were 3.7 and 5.6 g/kg dry matter, respectively. However, dietary phosphorus was
      utilized most efficiently (88%) at a dietary concentration of 2.5 g/kg dry
      matter. At the dietary phosphorus concentration that resulted in maximum
      phosphorus deposition (5.6 g/kg dry matter), phosphorus utilization was about
      60%. Supplemental phosphorus from dibasic sodium phosphate was completely
      available to trout which must be considered in formulating recommendations. Based
      on this work, 0.25 g available phosphorus/MJ digestible energy is recommended for
      trout diets.

PMID- 8558319
TI  - Caco-2 cell iron uptake from meat and casein digests parallels in vivo studies:
      use of a novel in vitro method for rapid estimation of iron bioavailability.
AB  - We developed a model for assessing iron bioavailability from foods which combines
      simulated peptic and intestinal digestion with measurement of iron uptake by Caco
      2 cell monolayers. Our objective was to further validate this model by
      determining if meat enhances Caco-2 cell iron uptake relative to casein. Caco-2
      cell monolayers were covered with Hank's balanced salt solution (HBSS) buffered
      with HEPES, pH 7.4. An upper chamber was created over the cells by fitting the
      bottom of a Costar Transwell insert with a 12,000-14,000 molecular weight cut-off
      dialysis membrane. This membrane allowed low molecular weight iron complexes to
      diffuse into the media bathing the cells and prevented damage to the cells from
      the digestive enzymes. Prior to digestion, each sample (homogenate of beef,
      chicken, fish or casein) was mixed with 59FeCl3 to achieve an iron concentration
      of 10 mumol/L. Following pepsin digestion (pH2), pH was adjusted to 7.4,
      pancreatic enzymes and bile extract were added to each digest, and an aliquot was
      then introduced into the upper chamber of the culture dish. During this
      intestinal digestion period, 59Fe uptake occurred from iron that dialyzed into
      the lower chamber. The 59Fe uptake from beef, chicken and fish digests was 300
      400% of the 59Fe uptake from a casein digest. Our results parallel human
      absorption studies indicating that meat enhances iron absorption. The results
      suggest that digestion products of the meat proteins were at least partially
      responsible for the enhancement of iron uptake. Overall, this study supports the
      usefulness of our model as a means of assessing iron bioavailability.

PMID- 8558320
TI  - Dietary fish oil confers direct antiarrhythmic properties on the myocardium of
      rats.
AB  - This study tested the hypothesis that in vivo antiarrhythmic effects of dietary
      fish oil can be attributed directly to changes in myocardial properties. Sixty
      adult male rats were fed a fish oil diet (FO), an isoenergetic saturated fat diet
      (SAT) or a low fat reference diet (REF) for 16 wk. hearts isolated from these
      rats were perfused with washed porcine erythrocytes (0.4 hematocrit) in working
      heart mode. Dietary fish oil prevented reperfusion-induced ventricular
      fibrillation (VF) (% of rats with VF: REF 50%, SAT 80% P = 0.35, FO 0% P < 0.05 n
      = 10) and reduced arrhythmias in ischemia. In a separate set of hearts from rats
      fed the three diets, FO increased while SAT reduced the stimulation threshold for
      programmed electrical induction of VF during control perfusion compared with REF
      (mean +/- SD: REF 7.1 +/- 0.2 mA; SAT 5.8 +/- 0.2 mA, P < 0.001; FO 15.1 +/- 1.0
      mA, P < 0.001, n = 10) and during subsequent ischemia (REF 5.9 +/- 0.2 mA; SAT
      3.8 +/- 0.3 mA, P < 0.001; FO 8.9 +/- 0.2 mA, P < 0.001, n = 10). The isolated
      working heart model used physiological workload and oxygenation but excluded
      extracardiac influences. Dietary fish oil prevented the initiation and reduced
      the severity of arrhythmias in the isolated hearts in response to a variety of
      stimuli. These results establish that irrespective of any effects on blood
      pressure or platelet function in vivo, dietary fish oil directly affects
      myocardial properties which may contribute to observed clinical reductions in
      cardiac mortality associated with fish consumption.

PMID- 8558321
TI  - Reliability of the doubly labeled water method for the measurement of total daily
      energy expenditure in free-living subjects.
AB  - The reliability of the doubly labeled water method for measuring total daily
      energy expenditure (TDEE) was measured in six adult women at a 6-mo interval. The
      contribution of random error to reliability was assessed by repeating each
      isotopic analysis. Physiologic variation was calculated from the difference
      between the total variance and the analytic variance. In addition, postabsorptive
      resting metabolic rate and thermic effect of a meal were measured to partition
      the physiologic variation in TDEE into its three components. No seasonal effect
      (summer-winter) in TDEE was detected in these six subjects. The within-subject
      coefficient of variation for TDEE was 7.8%, of which physiologic variation was
      6.4%. Within-subject variation in physical activity was the major source of
      variation in TDEE. Review of the 16 published studies, in which at least two
      measurements of TDEE by doubly labeled water were performed in each subject,
      indicated that the reliability of the method is 7.8%, except under conditions of
      high water flux. Care, however, must be taken to ensure that the analytic
      contribution does not inflate this figure in any given laboratory.

PMID- 8558322
TI  - Analytical instruments for stable isotopic tracers in mineral metabolism.
AB  - Thermal ionization mass spectrometry (TIMS) is the best of four currently used
      techniques for obtaining results of high accuracy and precision in studies of
      metal metabolism. TIMS is also the most general technique because it allows
      measurements of all the metallic elements of interest. The highest absolute
      sensitivity as well as the ability to determine multiple elements are
      simultaneously obtained with inductively coupled plasma mass spectrometry (ICP
      MS). Current results with this technique show that, although element
      quantification may be done with acceptable accuracy and precision, use of ICP-MS
      in metabolic studies at low levels of isotopic labels may be limited. The most
      favorable elements for study using ICP-MS in metabolic studies appear to be Mg,
      Zn and possibly Fe. Use of this technique is limited further by isobaric
      interferences from plasma jet ion molecule reactions, and metabolic studies of Ca
      are particularly limited. Acceptable levels of accuracy and precision have been
      obtained from fast atom bombardment-secondary ion mass spectrometry (FAB-SIMS),
      which has allowed these approaches to be used in metabolic studies of ZN, Fe and
      Ca, but the approaches are ultimately limited by hydride isobaric interferences.
      Both FAB-SIMS and gas chromatography-mass spectrometry of metal chelates have the
      advantage of using widely available instrumentation. GC-MS of metal chelates has
      been shown to be useful in studies of Cr and Se metabolism and for the
      determination of a number of other metals. Values of accuracy and precision from
      use of this approach have been satisfactory.

PMID- 8558323
TI  - Stable isotopic tracers for studies of glucose metabolism.
AB  - Because of its unique metabolism, glucose illustrates the advantages and
      limitations of stable isotopic tracers for in vivo studies. The present review
      describes the application of stable tracers in studies of glucose metabolism. The
      natural abundance of these tracers requires that careful attention be given to
      the dose of the tracer and the impact of the background abundance on
      measurements. The consequence of the natural variation of 13C abundance on
      measurements in vivo is described, as is the application of multilabeled
      molecules to estimate kinetics and intrahepatic precursor pool enrichments. The
      final section outlines recently described methods of estimation of
      gluconeogenesis.

PMID- 8558324
TI  - Soybean isoflavones improve cardiovascular risk factors without affecting the
      reproductive system of peripubertal rhesus monkeys.
AB  - Although the beneficial effects of dietary soybean protein compared with animal
      proteins on plasma lipids, lipoproteins and atherosclerosis have been known for
      about 50 years, it has been uncertain whether these effects are due to its amino
      acid concentrations or other components in soybeans. To assess the effect of
      soybean protein's alcohol-extractable components (including the isoflavonic
      phytoestrogens genistein and daidzein) on plasma lipid and lipoprotein
      concentrations and to establish its lack of effect on the reproductive system, we
      fed 27 peripubertal male and female rhesus monkeys moderately atherogenic diets
      in which the source of dietary protein was a soy isolate (20% by weight), either
      containing phytoestrogens (also termed isoflavones) or with the phytoestrogens
      removed by alcohol extraction. The study was a crossover design with each period
      lasting for 6 mo. The phytoestrogen-intact soy protein (compared with the alcohol
      extracted soy protein) had favorable effects on plasma lipid and lipoprotein
      concentrations, specifically by significantly reducing LDL+VLDL cholesterol
      concentrations in both males and females (approximately 30-40% lower),
      significantly increasing high density lipoprotein cholesterol (HDLC)
      concentrations for females (approximately 15% higher) and significantly lowering
      total plasma cholesterol (TPC):HDLC ratios (approximately 20% lower for males and
      50% lower for females). The phytoestrogens had no adverse effects on the
      reproductive systems of either the males or females, as evaluated by reproductive
      hormone concentrations and organ weights at necropsy. Thus, the isoflavones in
      soy protein improve cardiovascular disease risk factors without apparent
      deleterious effects on the reproductive system of peripubertal rhesus monkeys.

PMID- 8558326
TI  - Biotin deficiency decreases ornithine transcarbamylase activity and mRNA in rat
      liver.
AB  - Biotin deficiency is well known as a cause of hyperammonemia, but there has been
      no report on the effect of biotin deficiency on hepatic ureagenesis. In this
      study, we examined the changes in the activities and gene expression of urea
      cycle enzymes using rats fed raw egg white as a model of biotin deficiency. All
      rats were made biotin-deficient by feeding them an avidin-containing diet for 6
      wk. The rats were divided into two groups at the beginning of this experiment:
      biotin-deficient rats (BD rats) and biotin-supplemented rats (BS rats) which were
      treated with biotin once a day at a dose of 1 mg per rat intraperitoneally. The
      plasma ammonia concentration of the BD rats (92.8 +/- 12 mumol/L) was
      significantly higher than that of BS rats (63.9 +/- 16 mumol/L, P < 0.05). The
      activities of ornithine transcarbamylase (OTC) was significantly lower in the
      liver of the BD (110.2 +/- 5.5) rats than in the BS rats (154 +/- 3.8 U/mg
      protein, P < 0.01). Activities of the other urea cycle enzymes were not
      significantly different in the two groups. OTC gene expression in the liver of BD
      rats was 40% lower than in BS rats (P < 0.05). These data suggest that biotin
      deficiency decreases OTC activity and the amount of OTC mRNA.

PMID- 8558325
TI  - Modulation of lysyl oxidase by dietary copper in rats.
AB  - Lysyl oxidase levels were estimated in rat tissues using an enzyme-linked
      immunosorption assay (ELISA) and a functional assay standardized against known
      amounts of purified lysyl oxidase. High concentrations of lysyl oxidase (> or =
      150 micrograms/g of tissue or packed cells) were detected in connective tissues,
      such as tendon and skin. Values for aorta, kidney, lung and liver ranged from 30
      to 150 micrograms/g of tissue; values for skeletal muscle and diaphragm were < 30
      micrograms/g tissue. Purified rat skin lysyl oxidase catalyzed the release of 50
      100 Bq of tritium per micrograms enzyme in assays that used 3H-elastin-rich
      substrates. In dense connective tissues, good agreement was obtained for the
      values from ELISA and those derived from measurements of functional activity in
      aorta, lung, skin and tendon (r2 > 0.9). When egg white-based experimental diets
      containing 2 or 10 micrograms/g added copper were fed to weanling rats, values
      for skin lysyl oxidase functional activity in the group fed 2 micrograms/g added
      copper were one-third to one-half the values for skin lysyl oxidase functional
      activity in rats fed 10 micrograms/g copper. This reduction in lysyl oxidase
      activity, however, had minimal effect on indices of collagen maturation in rat
      skin, e.g., collagen solubility in neutral salt and dilute acid or the levels of
      acid stable cross-links. Moreover, copper deficiency did not influence the steady
      state levels of lysyl oxidase specific mRNA in rat skin or the apparent amounts
      of lysyl oxidase in rat skin as determined by ELISA. These observations
      underscore that the concentration of lysyl oxidase is relatively high in dense
      corrective tissues, and although decreasing dietary copper influences functional
      activity, there is little apparent effect on the production of lysyl oxidase
      protein.

PMID- 8558327
TI  - Methionine reduces the valproic acid-induced spina bifida rate in mice without
      altering valproic acid kinetics.
AB  - The antiepileptic drug valproic acid (VPA) is an established human teratogen
      causing spin bifida aperta. We recently developed a mouse model in which spina
      bifida aperta and occulta are induced with VPA. In a search for protection
      against neural tube defects, we investigated the effect of methionine on the
      incidence of VPA-induced spina bifida in the mouse. To induce spina bifida, we
      injected VPA (350 mg VPA-Na/kg body weight) subcutaneously three times on d 9 of
      gestation at 0, 6 and 12 h. In some mice, L-methionine (3 x 70 mg/kg body weight)
      was injected intraperitoneally 30 min before each VPA administration. When
      fetuses were examined on d 18, methionine treatment slightly reduced the VPA
      induced spina bifida aperta rate from 5 to 1% (P > 0.05, no significant
      difference). The incidence of VPA-induced spina bifida occulta (90%) was
      significantly lower (28%) when methionine was also administered (P < 0.05).
      Examination on d 10 showed that the number of embryos in the mice administered
      VPA and methionine having an open neuroporus posterior was significantly lower
      than in mice administered VPA alone (P < 0.05). Pharmacokinetic studies indicated
      that VPA concentrations in maternal plasma and embryo did not differ between the
      two groups. Methionine reduces VPA-induced spina bifida in mice without altering
      VPA kinetics.

PMID- 8558328
TI  - Higher postpartum hepatic triacylglycerol concentrations in dairy cows with free
      rather than restricted access to feed during the dry period are associated with
      lower activities of hepatic glycerolphosphate acyltransferase.
AB  - We investigated the activities of hepatic glycerolipid synthesizing enzymes
      during postpartum fatty liver development in 10 high-producing dairy cows that
      had free access to feed during the dry period; a parallel group of 8 control cows
      was fed according to recommended energy requirements. After calving, both test
      and control cows had free access to feed. In the period of 10-14 wk before
      calving, voluntary dry matter intake of the test cows was 20.6 kg/d (SEM 0.42);
      the restricted control cows received 7 kg/d. Postpartum triacylglycerol
      concentrations in liver biopsies were one- to twofold higher in the test than in
      the control cows. The higher plasma nonesterified fatty acid (NEFA)
      concentrations after parturition in the test vs. the control group were probably
      caused by a more negative energy balance in the test cows, which was associated
      with a slightly lower postpartum dry matter intake. After calving, hepatic
      mitochondrial glycerolphosphate acyltransferase (GPAT) activities were
      significantly lower in the test than in the restricted control cows. A low GPAT
      activity may divert fatty acids from esterification to beta-oxidation to protect
      the hepatocytes against further accumulation of triacylglycerols. The activities
      of hepatic phosphatidate phosphohydrolase, diacylglycerol acyltransferase, and
      cholinephosphate cytidylyltransferase were not different in the two groups. This
      study indicates that in cows given free instead of restricted access to feed
      during the dry period have a postpartum hepatic triacylglycerol accumulation that
      is mainly determined by a raised hepatic uptake of plasma NEFA.

PMID- 8558329
TI  - Dietary casein phosphopeptides prevent bone loss in aged ovariectomized rats.
AB  - The effect of dietary Ca-bound casein phosphopeptides (CaCPP) on the bones of
      aged ovariectomized (OVX) rats was studied as a model for post-menopausal bone
      loss. Three groups of ovariectomized rats were fed a control diet or one of two
      experimental diets, and one group of sham-operated rats (SHAM) was fed the
      control diet. The experimental diets contained 0.5% Ca and 0.4% P. In one diet,
      CaCPP was the sole source of calcium and provided 62.5% of dietary phosphorus
      (CaCPP diet). In the other, Ca-free CPP provided 100% of dietary phosphorus (Ca
      free CPP diet). In the control diet, CaCO3 and KH2PO4 were used. During a 17-wk
      feeding period, there was little change in femoral bone mineral densities (BMD)
      of ovariectomized rats fed CaCPP and Ca-free CPP, or in the SHAM rats fed the
      control diet, whereas the bone mineral densities in the control ovariectomized
      rats decreased with time. Some of the segmental bone mineral densities of the
      excised femurs from the rats fed CaCPP were significantly higher than those from
      the control ovariectomized rats, but the values of the Ca-free CPP group were
      similar to those of the control ovariectomized rats. In the Ca-free CPP group,
      the discrepancy in bone mineral densities obtained between in vivo results and
      excised specimens might have been the result of a loss in bone mass due to their
      significant loss in body weight. There were no significant differences in serum
      inorganic phosphorus, alkaline phosphatase activity, osteocalcin or 1 alpha-25
      dihydroxycholecalciferol concentrations among the ovariectomized groups. In the
      CaCPP and Ca-free CPP groups, urinary phosphorus excretion decreased and urinary
      calcium excretion increased significantly with time. The inhibitory effect on
      bone loss in aged ovariectomized rats could be due to the effects of dietary
      CaCPP on phosphorus and calcium metabolism.

PMID- 8558331
TI  - Neonatology by rumor or reality: evidence-based decision making.

PMID- 8558330
TI  - Vitamin A deficiency diminishes the salivary immunoglobulin A response and
      enhances the serum immunoglobulin G response to influenza A virus infection in
      BALB/c mice.
AB  - We examined the effect of vitamin A deficiency on the secretory immunoglobulin
      (Ig) A and serum IgG response to influenza A virus infections in BALB/c mice.
      Mice fed a vitamin A-deficient (VAD mice) or a control diet were inoculated with
      influenza virus at 7 or 9 wk of age when serum retinol concentration had dropped
      to < or = 0.35 mumol/L in the VAD mice. The influenza-specific salivary IgA
      response to a mild infection (intranasal inoculation without anesthesia) was not
      significantly lower in the VAD group (5.3 +/- 2.1% of total IgA 4 wk after
      infection) than in the control group (10 +/- 11%, P > 0.05). In a separate
      experiment, this salivary IgA response was significantly lower in the VAD mice
      (0.3 +/- 0.4% of total IgA) following a more severe infection (intranasal
      infection while under anesthesia) than it was in control mice (4.2 +/- 4.6% of
      total IgA, P < 0.0001). In contrast, the concentration of total salivary IgA was
      uniformly greater in the VAD mice than in the control mice during both the mild
      infection (VAD, 17 +/- 6 mg/L vs. control, 8 +/- 11 mg/L at 3 wk, P < 0.0001) and
      the severe infection (VAD, 38 +/- 30 mg/L vs. control, 9 +/- 7 mg/L, P < 0.0001).
      Similarly, the influenza-specific serum IgG response was also greater in the VAD
      mice than in the control mice during both the mild infection (VAD, 194 +/- 91
      mg/L vs. control, 79 +/- 95 mg/L at 5 wk, P = 0.0002) and the severe infection
      [VAD median, 202 mg/L (25th, 75th percentiles, 153, 409 mg/L) vs. control, 123
      mg/L (42, 165 mg/L), P = 0.0023]. Thus VAD significantly impairs the secretory
      IgA response to influenza infection but modestly increases the serum IgG response
      to the same infection.

PMID- 8558332
TI  - Neonatal outcome of premature infants of mothers with preeclampsia.
AB  - Our objective was to compare the outcome of premature infants of mothers with
      preeclampsia and hypertension with properly matched controls to examine whether
      infants of mothers with preeclampsia are at a lesser risk. We designed a
      retrospective cohort study of 99 infants of mothers with preeclampsia and
      hypertension (IHM) at < or = 36 weeks' gestation. Infants of nonhypertensive
      women matched for gestational age, gender, asphyxia, maternal diabetes mellitus,
      twin gestation, and mode of delivery served as controls. Data were analyzed by
      dividing all cases into three gestational age groups: group I, 26 to 30 weeks'
      gestation (IHM n = 21, control n = 39); group II, 31 to 33 weeks (IHM n = 32,
      control n = 61); and group III, 34 to 36 weeks (IHM n = 46). Because detailed
      data on nonhypertensive infants at 34 to 36 weeks' gestation were available only
      for intensive care unit admissions, group III was excluded from the comparative
      analysis. The incidence of hyaline membrane disease was significantly lower in
      IHM compared with the controls in groups I and II (group I, 19.1% vs 46.2%, p <
      0.005; group II, 12.5% vs 32.8%, p < 0.04). Symptomatic patent ductus arteriosus
      occurred less frequently in groups I and II compared with controls (group I,
      28.6% vs 46.2%, p < 0.001; group II, 3.1% vs 13.1%, p < 0.005). Intraventricular
      hemorrhage was less frequent in group I compared with controls (4.8% vs 20.5%, p
      < 0.001). The incidence of intraventricular hemorrhage in group II was similar at
      3.1% versus 1.6% for controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8558333
TI  - Postpartum depression: issues in clinical assessment.

PMID- 8558334
TI  - Enteral administration of recombinant erythropoietin to preterm infants.
AB  - In six preterm infants we tested the hypothesis that, as is the case in infant
      rats, orally administered recombinant erythropoietin (EPO) would be absorbed and
      would stimulate erythropoiesis. Three study subjects were younger than 1 week old
      and had never been fed and three were more than 1 month old and were receiving
      enteral feedings totally. Two hours after the administration of large doses of
      EPO (1000 U/kg body weight) only a small increase in serum EPO concentrations
      (from 6.3 +/- 0.9 to 13.3 +/- 2.8 mU/ml, mean +/- SEM) was observed. No further
      increases were observed 4, 6, 12, or 24 hours after the administration. No
      increases in reticulocyte count or hematocrit were observed after 10 days of EPO
      administration. We conclude that, unlike the situation in infant rats, enterally
      administered recombinant EPO is not absorbed in significant amounts by human
      preterm infants. Therefore oral administration will not be an effective
      substitute for subcutaneous or intravenous EPO administration in preterm infants.

PMID- 8558335
TI  - Extravascular extravasation of fluid as a complication of central venous lines in
      the neonate.
AB  - The use of central venous lines in neonatal intensive care is widespread. We
      report a series of 11 infants in whom extravasation of fluid developed presumably
      as a result of the central line. There were six cases of pericardial effusion
      with a 67% mortality rate and five cases of pleural effusion with no mortality,
      for a total extravasation incidence of 1.1% for central lines placed during a 5
      year period. The highest incidence of effusion occurred with polyethylene
      catheters, but all types of catheters resulted in effusion. This report
      emphasizes the serious morbidity and mortality of these complications of central
      venous lines.

PMID- 8558336
TI  - Treatment for hyperemesis gravidarum in the home: an alternative to
      hospitalization.
AB  - Our objective was to determine whether medical therapy in the home for patients
      with hyperemesis gravidarum is safe, efficacious, and cost effective compared
      with hospitalization. In this retrospective, matched control study 50 women with
      hyperemesis were treated in the home and were matched for gravidity, gestational
      age, and weight loss from prepregnancy weight with 47 patients who were
      hospitalized for traditional treatment. Both groups had similar intravenous fluid
      and medical support until they could tolerate adequate oral intake. Women in the
      home had 9.7 +/- 8.0 days of intravenous therapy compared with 9.5 +/- 6.2 days
      in hospitalized patients (not significant). The mean percent of weight loss at
      initiation of therapy was similar in both groups (4.6% +/- 5.7% vs 4.5% +/- 6.1%,
      not significant). The mean weight change during therapy in the home group was +
      1.0 +/- 4.3 pounds compared with +1.2 +/- 8.6 pounds in the hospitalized group
      (not significant). The only complication was infiltration of the intravenous
      site, the occurrence of which was similar in the two groups (40% vs 57%, not
      significant). At discontinuation of therapy 90% of the home patients no longer
      required any supportive therapy; 10% (n = 5) required hospitalization because of
      relapse. The cost of therapy was significantly lower for patients in the home
      group ($708 +/- $533 vs $2701 +/- $1717, p < 0.001). These data show that
      management of hyperemesis in the home is both safe and efficacious. Furthermore,
      successful therapy can be achieved in the home at a significantly reduced cost.

PMID- 8558337
TI  - Splinting therapy for congenital auricular deformities with the use of soft
      material.
AB  - Congenital auricular deformities present serious esthetic problems. To avoid
      surgical correction, splinting during the early neonatal period has been
      attempted. We describe the results and follow-up of splinting therapy with a
      special soft material in 30 neonates, as compared with results in a control group
      of 20 untreated newborn infants. Good results were achieved in 85% of the
      patients and sufficient results in 15% when the treatment was continuous over the
      entire 4-week period. However, when treatment was partial or discontinuous, only
      10% had good results. None of the infants in the control group showed spontaneous
      improvement during the period of study. Moreover, early initiation of treatment
      (first week of life) proved more effective than later treatment (second week of
      life). Strong parental cooperation and close follow-up are also important for
      success.

PMID- 8558338
TI  - Natal status of infants of cocaine users and control subjects: a prospective
      comparison.
AB  - Cocaine use by pregnant women has increased dramatically in recent years. To
      assess the effect of maternal cocaine use on infant outcome, we enrolled 224
      women (105 cocaine users, 119 control subjects) and their infants (all of 34
      weeks or more gestational age and nonasphyxiated) in a prospective, blinded
      study. Results showed that infants exposed to cocaine were more likely to be
      admitted to the newborn intensive care unit, be treated for congenital syphilis,
      have a greater length of stay, and be discharged to a person other than the
      mother (all p < 0.01). Birth weight and head circumference, adjusted for
      gestational age, were smaller in the infants exposed to cocaine than in control
      infants (p < 0.001). After statistically controlling for cigarette use and other
      confounders, however, the odds of infants exposed to cocaine and control infants
      having birth weight and head circumferences less than the 25th percentile for
      gestational age did not differ (both p > 0.80). Infants of cocaine-using mothers
      and control subjects had a similar incidence of abnormal cranial and renal
      ultrasonographic findings and abnormal pneumocardiograms (all p > or = 0.32). We
      conclude that in this cohort of nonasphyxiated infants of 34 weeks or more
      gestational age, infants exposed to cocaine had more medical and social problems
      than control infants but did not differ statistically in the incidence of severe
      growth retardation, abnormal cranial or renal ultrasonographic findings, or
      abnormal pneumocardiograms. We suggest that natal interventions for the
      nonasphyxiated term and near-term infant exposed to cocaine should include a
      careful history and physical examination, follow-up plans, and social service
      involvement.

PMID- 8558339
TI  - The effect of a comprehensive prematurity prevention program on the number of
      admissions to the neonatal intensive care unit.
AB  - The null hypothesis of this study was that a prematurity prevention program that
      uses computerized prenatal risk assessment, educational interventions
      administered on a weekly basis by telephone, enhanced nutritional support, and
      referral to a perinatologist whenever necessary will result in no difference in
      the number of neonates admitted to the neonatal intensive care unit (NICU). A
      retrospective cohort study was designed to compare the number of admissions to
      the NICU for the 12 months before initiation of the prematurity prevention
      program with those during the first 12 months of the full working program.
      Compared with the year before program initiation, the prematurity prevention
      program resulted in a 56% reduction in the number of NICU admissions, a 49%
      reduction in preterm deliveries with subsequent admission of the infant to the
      NICU, and a 59% reduction in NICU hospital days. In addition, there was a 38%
      reduction in preterm deliveries caused solely by preterm labor. The null
      hypothesis is rejected because a comprehensive prematurity prevention program
      resulted in a significant reduction in NICU admissions, preterm deliveries with
      admission to the NICU, and NICU hospital days.

PMID- 8558340
TI  - Decreased respiratory tolerance from intermittent asphyxia in rat sucklings.
AB  - To study the respiratory tolerance of rat pups to intermittent asphyxia induced
      by exposure to closed rebreathing, we randomized newborn rats from four litters
      into two treatment groups. Respiratory tolerance was defined as the time interval
      during asphyxia until the first episode of 30 seconds of apnea. Rats in the
      experimental group were asphyxiated once daily during the first 4 days of life.
      Rats in the control group were asphyxiated once on day 4 of life. Pups exposed to
      intermittent asphyxia had a significant reduction in respiratory tolerance
      compared with that of littermates asphyxiated once at the same age. These
      findings suggest that the ability of the young mammal to withstand re-exposure to
      asphyxia may be impaired.

PMID- 8558341
TI  - Incidental diagnosis of asymptomatic neonatal cholelithiasis: case report and
      literature review.
AB  - A case of asymptomatic cholelithiasis detected incidentally at the age of 3 days
      in an otherwise healthy newborn infant is presented. The hospitalization was
      uneventful. At follow-up the biliary stones had completely resolved at the age of
      3 months with no symptoms. Fourteen similar cases of incidentally diagnosed
      neonatal cholelithiasis were found in the literature. Clinical course was benign;
      12 cases (86%) were asymptomatic and eight (57%) had spontaneous resolution by
      the age of 6 months. We conclude that incidentally diagnosed neonatal
      cholelithiasis usually has a benign course with about a 50% chance of spontaneous
      resolution during the first 6 months of life. In cases of persistent gallstones
      by age 6 months, no treatment is needed except for long-term follow-up.

PMID- 8558342
TI  - Guidelines on the care of anencephalic infants: a response to baby K.

PMID- 8558343
TI  - Cognitive failure to thrive in high-risk infants: the importance of the
      psychosocial environment.
AB  - We evaluated early social risk assessment as a predictor of cognitive development
      in high-risk infants. A social worker assessed social risk in 122 infants before
      discharge from a neonatal intensive care unit. Infants were evaluated at ages 12
      and 36 months adjusted for prematurity. We found no difference in 12-month
      cognitive development among medical, neurologic, or social risk groups. However,
      from 12 to 36 months there was a significant decline in mean developmental
      quotient in the groups with social risk alone, neurologic and social risk, and
      medical and social risk, but not in the groups with medical or neurologic risks
      without social risk. Social risk assessment correctly predicted 36-month
      cognitive outcome in 71% of infants who had normal findings at 12 months. We
      conclude that neonatal social risk assessment can help identify infants at
      highest risk for cognitive retardation and is particularly important for infants
      who have medical or neurologic problems.

PMID- 8558344
TI  - Acute pancreatitis caused by biliary ascaris in pregnancy.
AB  - Ascaris lumbroicoides is the most prevalent human parasite worldwide. Although
      usually asymptomatic, ascaris is responsible for a variety of severe
      complications such as intestinal obstruction, cholangitis, or hepatitis, which
      are caused by worm migration. This article is the second known case report of
      pancreatitis caused by biliary ascaris during pregnancy. We also review the
      pathophysiology of this disease and review the various treatment modalities
      available for pregnant patients. We believe that because of the growing influx of
      immigrants from endemic areas into the United States, the clinician needs a basic
      understanding of the etiology, diagnosis, and treatment of biliary ascarasis.

PMID- 8558345
TI  - Genetics casebook. Duplication-deletion syndromes.

PMID- 8558346
TI  - Special imaging casebook. Neonatal hemochromatosis.

PMID- 8558347
TI  - Ventilatory management casebook. Systemic air embolism: a potentially fatal
      complication of ventilator therapy.

PMID- 8558348
TI  - Distribution of astigmatism in the adult population.
AB  - We have quantified statistically the astigmatic frequency distribution. Vectorial
      analysis was used, as it enables formal multivariate statistical techniques to be
      applied to astigmatic data, allowing the simultaneous inclusion of both modulus
      and axis in the analytical procedure. These methods were applied to population
      data for each of total, corneal, and residual astigmatism from a sample of 198
      adults. Right and left eyes were analyzed separately. All the distributions were
      found to depart significantly from a normal distribution. All the distributions
      were significantly leptokurtic (p < 0.005), and the distributions of total right
      eye, corneal right eye, and residual left eye astigmatism were also found to be
      significantly skewed (p < 0.05). Significant mild correlations were found between
      total and corneal astigmatism (p < 0.05). These findings add to the database of
      knowledge of astigmatic refractive error and may be of interest to those
      investigating refractive-error development.

PMID- 8558349
TI  - Fundus reflectance and the measurement of crystalline lens density.
AB  - We have developed an optical technique for measuring the in vivo absorption of
      the human crystalline lens based on using the retina as a reflector for a double
      pass measurement of lens density. We compare results obtained by the
      reflectometric technique with results obtained in the same subjects by a
      psychophysical method. We find that the estimates obtained with the two
      techniques are highly correlated, and both measure similar effects of aging on
      the optical density of the lens. In addition, we show that the significant
      variations in retinal reflectance attributable to differences in ocular
      pigmentation and drusen have only a minor effect on the estimate of lens optical
      density. However, correcting retinal reflectances for the effect of lens
      absorption shows that the effect of lens absorption may be overestimated with
      both methods. The overestimation may arise from inaccuracies in the shape of the
      assumed lens spectrum.

PMID- 8558350
TI  - Satisfaction with complete immediate dentures and complete immediate
      overdentures. A 1 year survey.
AB  - The aim of this study was to evaluate denture satisfaction over a 1 year period
      after extraction of the last teeth. Seventy-four patients who required immediate
      denture therapy in the mandible were randomly treated, (1) with complete
      immediate dentures (22); (2) with immediate overdentures on two lower canines
      without attachments (26); or (3) with immediate overdentures on two lower canines
      provided with Dyna direct magnetic attachments, inserted on the abutments 9
      months after treatment (26). Denture satisfaction was estimated by means of
      questionnaires, filled out by each patient at certain periods, starting before
      treatment and ending 1 year after denture insertion. After 1 year approximately
      85% of the patients in the three groups were satisfied with their dentures, had
      got used to them and could eat well. This phenomenon was constant over the whole
      first year period. No differences in denture satisfaction were found between the
      three groups. It can be concluded that although patients who receive immediate
      complete dentures might experience a lot of discomfort during the first year of
      edentulousness, they are satisfied, in general, with their dentures independent
      of the treatment procedure.

PMID- 8558351
TI  - Delayed implants in the anterior maxilla with the IMZ-implant system: a
      radiographical evaluation.
AB  - One hundred and seventy-three IMZ-implants in 81 patients, placed in the anterior
      region of the maxilla, were evaluated radiographically by two observers.
      Radiographs were evaluated at three intervals, namely at the time of implant
      placement, the time of prosthetic restoration and at the latest available
      radiograph, on average 2 1/2 years after implant placement. In this study
      marginal bone height and the type of radiolucency adjacent to the implant were
      determined. Both observers were able to classify the marginal bone height (mesial
      and distal) and the distinctive type of resorptive defects to an acceptable level
      of agreement, with Cohen's kappa ranging between 0.48 and 0.69. It was found
      that, at the most recent visit to the clinic, angular-shaped resorptive defects
      are found mesially and/or distally of the implants at approximately 25% of the
      implants. At this stage 20.7% of the mesial implant sites and 27.9% of the distal
      implant sites show marginal bone heights less than three-quarters of the implant
      length. These findings do not fully underscore and sometimes even contradict the
      clinical observations which were considered highly satisfactory.

PMID- 8558352
TI  - Psychological factors related to the prevalence of temporomandibular joint
      sounds.
AB  - This study focuses on the association between psychological factors and TMJ
      sounds, and the most suitable research design to establish this relation. A
      traditional research design is simulated to demonstrate how self-report may bias
      findings. A refined design is presented to obtain unbiased estimates of the role
      of psychological variables. In the 'naive' design the importance of psychological
      variables was overestimated and the role of physiological variables was
      underestimated. It was concluded that future studies in the aetiology of TMJ
      clicking should abandon the use of self-report as a proxy for objective findings.
      With the refined design it was found that psychological factors play only a minor
      role in the prevalence of TMJ sounds. Findings do not support speculation about
      mechanisms that relate psychological factors to the presence of TMJ sounds.

PMID- 8558353
TI  - The rate of OH- ion release from lining materials containing calcium hydroxide.
AB  - Four light-cured calcium hydroxide and three chemically cured resin-based lining
      materials were compared for hydoxil ion (OH-) release. Results indicated that the
      chemically cured calcium hydroxide cements were capable of OH- release for a
      longer period than the light-cured resin bases. Alkaliner (a chemically cured
      liner) produced and maintained the highest alkaline environment in the long-term,
      whereas calcium fluoride liner and Basic-L (both resin-based) showed the lowest
      values of OH- ion release.

PMID- 8558355
TI  - Electromyographic analysis of the sternohyoid muscle and anterior belly of the
      digastric muscle in head and tongue movements.
AB  - The sternohyoid muscle and anterior belly of the left digastric muscle were
      electromyographically studied in 20 young adult volunteer individuals. A surface
      monopolar electrode and a needle monopolar electrode, inserted into the muscle
      mass 1.0 cm apart were employed. The muscles acted during the following movements
      of the tongue; protraction, lateral movements to either side, and placement of
      the tip of the tongue on the hard and soft palate. It was in the latter movement
      that the most significant action potentials of the sternohyoid muscle were
      observed, which coincided with a major displacement of the hyoid bone. Both
      muscles studied do not take part in the kinesiology of the head.

PMID- 8558354
TI  - Effect of components of resilient denture-lining materials on the growth, acid
      production and colonization of Candida albicans.
AB  - Variation in the components of soft lining materials, i.e. the size of polymer
      particles, the ethyl alcohol content of the liquids and the type of plasticizer,
      were investigated with respect to their effects on the growth and colonization of
      Candida albicans. Inhibitory effects on fungal growth and/or acid production were
      found to vary depending upon the components of soft lining materials. In
      particular, two plasticizers, benzyl benzoate (BB) and benzyl salicylate (BS),
      significantly decreased the growth rate, whereas the size of polymer particle had
      little effect on fungal growth. Ethyl alcohol content of liquid significantly
      affected the fungal growth and/or acid production depending upon the plasticizer
      used. For instance, in the case of BS, the antifungal effect was related to ethyl
      alcohol contents, whereas a reverse effect was observed with benzyl n-butyl
      phthalate (BBP). Further examination using scanning electron microscopy revealed
      that Candida blastospores colonized lining materials in the following two ways
      depending on the plasticizers used. On the BS and dibutyl phthalate (DBP)
      specimen, the blastospore of this yeast associated loosely, whereas, in the case
      of BB, BBP and butyl phthalyl butyl glycorate (BPBG), fungal blastospore tightly
      and invasively colonized onto the specimens. These results clearly demonstrated a
      relationship between components of soft lining materials and fungal growth and
      colonization.

PMID- 8558356
TI  - Changes in the position of the mental foramen as a result of alveolar atrophy.
AB  - The location of the mental foramen has often been claimed to be unaffected by
      alveolar atrophy. In the present study, the distances of the mental foramen and
      the mandibular canal from the lower cortex of the mandible were compared in a
      radiographed series of 40 edentulous elderly women with advanced alveolar atrophy
      and 40 elderly women who had 10 or more lower teeth left. The mental foramen was
      situated on average 3.8 mm lower in dentulous jaws than in dentulous jaws (P <
      0.0001). The mandibular canal was also situated lower in edentulous jaws, but the
      difference was not statistically significant. The results confirm the finding
      that the mental foramen seems to descend as a result of alveolar atrophy.

PMID- 8558357
TI  - Experimental occlusal interferences. Part IV. Mandibular rotations induced by a
      pliable interference.
AB  - In 12 subjects, a pliable, yet unbreakable, intercuspal interference (aluminum
      shim onlay splint; uniform height of 0.25 mm) was placed between either the right
      or left maxillary and mandibular second premolars and first molars. During brief
      and forceful biting (dynamic chewing stroke of about 20 kg force) the
      interference emulated a semisoft food bolus, and at the end of biting (subsequent
      static clenching stroke of about 20 kg force) it emulated a rigid metal
      interference. During dynamic/static biting, rotational electrognathography
      measured maximum frontal and horizontal plane torque of the right and left
      mandibular condyles. Eleven subjects (92%) showed frontal plane upward rotation
      (mean of 1.0 degree) of the condyle contralateral to the interference, and one
      subject (8%) showed frontal plane upward rotation (0.4 degree) of the condyle
      ipsilateral to the interference. Two subjects (17%) showed no horizontal plane
      rotation; seven subjects (58%) showed backward rotation (mean of 0.4 degree) of
      the condyle contralateral to the interference; and three subjects (25%) showed
      backward rotation (mean of 0.3 degree) of the condyle ipsilateral to the
      interference. It is suggested that, in the presence of an occlusal interference,
      mastication may have both short- and long-term detrimental effects.

PMID- 8558358
TI  - The anterior facial triangle: a method of cephalometric appraisal.
AB  - The purpose of this study was to introduce a simple cephalometric method to
      identify individually the possible rotations of the palatal and mandibular
      planes, using point nasion as a reference, without the need to include the Sella
      Nasion or Frankfort horizontal planes. Also, using this method, it was possible
      to detect the antero-posterior position of subspinale. A random sample of 150
      British school children aged 9-12 years was used. Lateral skull radiographs were
      taken. The lateral films were traced and digitzed. A mean shape outline +/- 1
      s.d. for the sample was produced and superimposed on the craniofacial centroid
      for all the digitized tracings. A facial triangle was established, joining nasion
      to posterior nasal spine and nasion to the anteroposterior position of the
      subspinale intersecting the line joining the posterior nasal spine and anterior
      nasal spine.

PMID- 8558359
TI  - Target-peptide-induced changes in the structure and dynamics of calmodulin as
      probed by frequency domain fluorimetry of bound Tb(III).
AB  - Tb(III) luminescence is used to probe the conformational change induced in the
      calcium regulatory protein calmodulin upon binding to a target peptide. The
      luminescence lifetime for Tb(III) measured by frequency domain fluorimetry
      increases from 1278 microseconds for the calmodulin complex to 1496 microsecond
      for the complex of calmodulin and M13, a peptide derived from the calmodulin
      target protein myosin light chain kinase. The intensity of the Tb(III) emission
      increases over the solution value by a factor of 726 and 891 when bound to
      calmodulin and to the complex of calmodulin and M13 respectively. The sensitivity
      of the Tb(III) decay rate to deuterated solvent was also measured and is
      consistent with a single water molecule bound to the metal in both the calmodulin
      and calmodulin-M13 complex. The most dramatic change induced by M13 is the
      threefold reduction in the width of the Tb(III) lifetime distribution, which is
      interpreted to be a target-peptide-induced annealing of the previously flexible
      metal-binding site.

PMID- 8558360
TI  - delta-Aminolevulinic acid induced fluorescence in tumour-bearing mice.
AB  - The potential of protoporphyrin IX fluorescence induced by the systemic
      administration of delta-aminolevulinic acid (ALA) for the detection of tumours
      was tested in three different murine models (MS-2 fibrosarcoma, L1210 leukaemia,
      and Lewis lung carcinoma). Time-gated fluorescence images were acquired up to 4 h
      after the intraperitoneal injection of ALA (200 mg (kg body mass (BM))-1). For
      comparison images were acquired also after the administration of 25 mg (kg BM)-1
      of haematoporphyrin derivative. The latter drug was characterized by better
      localization in the tumour area, leading to higher fluorescence contrast between
      neoplastic mass and surrounding healthy tissue, and consequently was preferable
      for tumour diagnosis in all the models under study.

PMID- 8558361
TI  - Natural fluorescence of white blood cells: spectroscopic and imaging study.
AB  - Autofluorescence has been proved to be an intrinsic parameter of biological
      substrates that may aid in both the characterization of the physiological state
      and the discrimination of pathological from normal conditions of cells, tissues
      and organs. In this work, the fluorescence properties of human white blood cells
      have been studied in suspension and on single cells at microscopy. The results
      indicate that suspensions of agranulocytes and granulocytes differ in the
      amplitude of the fluorescence signal on excitation at wavelengths in the range
      250-370 nm. The differences are particularly enhanced when excitation is
      performed in the 250-265 nm range. Microspectrofluorometric analysis, performed
      on single cells, allows several leukocyte families to be characterized.
      Lymphocytes, monocytes, neutrophils and eosinophils can be distinguished
      according to the intensity and spectral shape of the autofluorescence emission in
      the visible range from 440 to 580 nm. Both the nature and extent of the
      differences change when the excitation wavelength is moved from 366 to 436 nm.
      Differences in the intrinsic metabolic engagement, rather than in the cell
      dimensions, seem to be responsible for the differences observed between the
      leukocyte populations. The results identify interesting perspectives for
      autofluorescence as a discriminating parameter in the differential counting of
      human white blood cells.

PMID- 8558362
TI  - Chronic UVB irradiation induces superoxide dismutase activity in human epidermis
      in vivo.
AB  - In order to study the effects of repeated UVB exposures on the epidermal
      antioxidant defence system, we obtained epidermis samples from male volunteers
      who were exposed to chronic UVB irradiation. Chronic UVB irradiation was shown to
      be accompanied by induction of epidermal superoxide dismutase (SOD) activity in
      vivo, while the activities of the other antioxidant enzymes were not
      significantly changed. The repeated exposure of the epidermis to UVB irradiation
      was not accompanied by accumulation of products of lipid peroxidation reactions.
      As superoxide dismutase is of major importance in scavenging the reactive oxygen
      species, the UVB-induced changes in SOD activity might provide the epidermis a
      way of defending itself against the effects of chronic UVB irradiation.

PMID- 8558363
TI  - Inactivation of viruses by chemically and photochemically generated singlet
      molecular oxygen.
AB  - Inactivation of viruses in blood plasma can be achieved by photodynamic
      procedures using methylene blue (MB) or other photoactive dyes. Singlet molecular
      oxygen (1O2) probably contributes to the virucidal effects of photosensitization.
      We report the inactivation of herpes simplex virus type 1 (HSV-1) and suid herpes
      virus type 1 (SHV-1) by chemically generated singlet oxygen, produced by thermal
      decomposition of the endoperoxide of 3,3'-(1,4-naphthylidene)dipropionate
      (NDPO2). We demonstrate that viruses can be inactivated by 1O2 generated by
      chemiexcitation in a reaction in the dark, even in the presence of human plasma.
      Virus inactivation in phosphate-buffered saline (PBS) was enhanced when water was
      replaced by deuterium oxide (D2O) and diminished when human plasma or quenchers
      (imidazole or histidine) were added. The singlet oxygen quenching activities of
      plasma, imidazole and histidine correlated with their inhibitory effects on virus
      inactivation. The production of 1O2 was assessed by an indicator reaction: the
      bleaching of p-nitrosodimethylaniline (RNO) with imidazole as 1O2 acceptor. Virus
      inactivation and singlet oxygen generation of NDPO2 were compared with those of
      MB/light-mediated photosensitization. Based on similar amounts of 1O2 generated
      by either procedure, virus inactivation by MB/light was more effective. Virus
      inactivation by MB/light was not affected by type I quenchers (e.g. mannitol),
      but was inhibited by human plasma or singlet oxygen quenchers. Furthermore, in
      D2O-based PBS, virus inactivation was more effective than that in H2O. These
      observations confirm that singlet oxygen is involved in virus inactivation by
      MB/light. Taken together, the results demonstrate that singlet oxygen produced by
      either procedure is virucidal. The enhanced effect of the photochemical procedure
      suggests that, in addition to type II, type I reactions and/or the binding
      affinity of the dye for the virus contribute to virus killing by MB/light.

PMID- 8558364
TI  - Wavelength dependence of laser-induced DNA damage in lymphocytes observed by
      single-cell gel electrophoresis.
AB  - Human lymphocytes from a cell culture were irradiated with laser pulses of an Xe
      Cl excimer laser (308 nm) or a dye laser at wavelengths from 312 to 640 nm. After
      conversion of photoinduced DNA damage into DNA strand breaks the "comet assay"
      (single-cell gel electrophoresis) was used to determine the number of photons
      required to induce detectable DNA damage. Between 308 and 450 nm the number of
      photons necessary for DNA damage increases about 10,000 times from 2.14 x 10(8)
      to 2.85 x 10(12) photons. Between 308 and 318 nm the number of photons necessary
      to induce detectable DNA damage is proportional to e0.45 lambda. Between 340 and
      450 nm it is proportional to e0.05 lambda. No detectable damage was induced at
      540 and 640 nm after irradiation with 9900 kJ m-2. Two-photon effects are
      unlikely to play a significant role.

PMID- 8558365
TI  - In vivo damage to chorioallantoic membrane blood vessels by porphycene-induced
      photodynamic therapy.
AB  - Photodynamic therapy (PDT) was performed in the chick embryo chorioallantoic
      membrane (CAM) for the purpose of quantitative evaluation of several porphycenes
      as potential photosensitizers. Porphycenes are structural isomers of porphine
      possessing lower symmetry of the macrocycle and are characterized by 10-fold
      higher absorption at the therapeutic wavelengths for PDT (lambda > 630 nm). PDT
      induced damage to CAM blood vessels included vasoconstriction and blanching as
      was monitored during irradiation and videotaped. Image analysis techniques
      enabled us to follow PDT-induced constriction of vessel diameter (to 50%),
      reduction of blood perfusion (to 40% lower optical density) and shrinkage of
      implanted tumours (to 10% of their original area). The observed PDT efficacy of
      functionalized porphycenes is positively correlated with the number of polar
      substituents.

PMID- 8558366
TI  - Biochemical and spectroscopic characterization of the putative photoreceptor for
      phototaxis in amoebae of the cellular slime mould Dictyostelium discoideum.
AB  - Using sucrose gradient centrifugation, anion exchange chromatography on a SMART
      system, isoelectric focusing (IEF) and sodium dodecylsulphate polyacrylamide gel
      electrophoresis (SDS PAGE), a 45.5 kDa membrane protein was isolated from amoebae
      of the cellular slime mould Dictyostelium discoideum. The absorption spectrum of
      the isolated protein corresponds well with the action spectrum for the
      photoaccumulation of the amoebae of Dictyostelium discoideum showing a major peak
      between 405 and 412 nm and some minor peaks between 500 and 600 nm. The
      remarkable similarity of the two spectra leads to the hypothesis that the
      isolated protein-pigment complex may serve as a photoreceptor for amoebal
      phototaxis.

PMID- 8558367
TI  - Rat lens glycolysis after in vivo exposure to narrow band UV or blue light
      radiation.
AB  - UV radiation and short wavelength visible light are known to damage various
      tissues in the eye. This paper investigates the effect on rat lens glycolysis
      after in vivo exposure with 90 kJ m-2 narrow band UV radiation (UVB, 300 nm) and
      90 kJ m-2 blue light (435 nm) radiation. After exposure, all lenses were
      incubated in Medium 199. Samples of culture medium were withdrawn after 2, 4, 6 h
      and 5, 10, 20 h in two UVB studies and after 5, 10 and 20 h in a blue light
      study. Lactate is the major end product of lens glycolysis. Lactate was
      determined with a modified enzymatic-photometric method. Intralenticular lactate
      was determined in one UVB experiment. In the UVB experiments we found a lower
      lactate production in the exposed lenses 2-6 h after exposure. There was an
      accumulation of lactate inside UVB-exposed lenses after 6 h incubation compared
      with their contralateral lenses. No significant effect on lactate production was
      observed in the blue light experiment. CONCLUSIONS. UVB induced a reversible
      inhibition of glycolysis. UVB also induced an accumulation of lactate inside the
      lens. Blue light tended to increase glycolysis.

PMID- 8558368
TI  - The effects of aggregation, protein binding and cellular incorporation on the
      photophysical properties of benzoporphyrin derivative monoacid ring A (BPDMA).
AB  - Absorption, fluorescence and laser flash photolysis spectroscopies were used to
      investigate the effects of self-aggregation, binding to human serum albumin and
      incorporation in cancer cells on the photophysics of benzoporphyrin derivative
      monoacid ring A (BPDMA). Aggregation of BPDMA has been studied in mixtures of
      methanol and phosphate-buffered saline (PBS). The extent of aggregation was
      dependent on dye concentration and solvent composition, becoming particularly
      marked in mixtures containing less than 30% methanol. A dimerization constant Kd
      or 9 x 10(6) M-1 was determined by fluorescence experiments for BPDMA in pure
      PBS. In addition to spectral modifications, aggregation induces a lowering of the
      fluorescence and intersystem crossing quantum yields. Human serum albumin binds
      BPDMA with an association constant Kb of 5.2 x 10(5) M-1 in PBS. When bound to
      HSA, BPDMA displays photophysical properties very similar to the monomer in
      organic solvents. The molar ratio [HSA]/[BPDMA] corresponding to complete binding
      of the dye was determined to be approximately 10. Efficient generation of the
      triplet state of BPDMA was also observed from aqueous cellular suspensions
      containing incorporated photosensitizer.

PMID- 8558369
TI  - Effects of vacuum UV and UVC radiation on dry Escherichia coli plasmid pUC19. II.
      Mutational specificity at the lacZ gene.
AB  - The mutational spectra at the lacZ gene, induced either by vacuum UV at 160 nm or
      UVC at 254 nm in vacuum-dried preparations of Escherichia coli plasmid pUC19 DNA,
      have been characterized from 72 E. coli-propagated mutants by DNA sequencing. In
      plasmids irradiated in vacuum, vacuum UV is five times more mutagenic than UVC.
      In the UV-induced mutants, base substitutions largely predominate, with GC-->AT
      (G, guanine; C, cytosine; A, adenine; T, thymine) transitions being the most
      abundant type of base change for vacuum UV (61%) and UVC (47%). Most of the GC-
      >AT transitions appear to occur at dipyrimidine sites, which are located at the
      non-transcribed DNA strand. Some, but not all, hot spots for GC-->AT transitions
      are identical for vacuum UV and UVC. Frameshifts, resulting from a loss of the
      thymine residue, are specific for UVC (22%), and were not detected after
      treatment with vacuum UV. They occur predominantly at thymine runs of the
      transcribed DNA strand. Only a few deletions were detected following irradiation
      with vacuum UV (7.5%) and UVC (2%); however, their frequency is not enhanced
      compared with the spontaneous mutation spectrum. The data confirm the important
      role of base substitution mutations in UV-induced mutagenesis, which is not only
      valid for the UVC range, but extends towards the vacuum UV range.

PMID- 8558370
TI  - HepG2 human hepatocarcinoma cells: an experimental model for photosensitization
      by endogenous porphyrins.
AB  - Endogenous protoporphyrin IX (PpIX) synthesis after delta-aminolaevulinic acid
      (ALA) administration occurs in cancer cells in vivo; PpIX, which has a short half
      life, may thus constitute a good alternative to haematoporphyrin derivative (HPD)
      (or Photofrin). This study assesses the ability of the human hepatocarcinoma cell
      line HepG2 to synthesize PpIX in vitro from exogenous ALA, and compares ALA
      induced toxicity and phototoxicity with the photodynamic therapy (PDT) effects of
      HPD on this cell line. ALA induced a dose-dependent dark toxicity, with 79% and
      66% cell survival for 50 and 100 micrograms ml-1 ALA respectively after 3 h
      incubation; the same treatment, followed by laser irradiation (lambda = 632 nm,
      25 J cm-2), induced a dose-dependent phototoxicity, with 54% and 19% cell
      survival 24 h after PDT. Whatever the incubation time with ALA, a 3 h delay
      before light exposure was found to be optimal to reach a maximum phototoxicity.
      HPD induced a slight dose-dependent toxicity in HepG2 cells and a dose- and time
      dependent phototoxicity ten times greater than that of ALA-PpIX PDT. After 3 h
      incubation of 2.5 and 5 micrograms ml-1 HPD, followed by laser irradiation
      (lambda = 632 nm, 25 J cm-2), cell survival was 59% and 24% respectively at 24 h.
      Photoproducts induced by light irradiation of porphyrins absorb light in the red
      spectral region at longer wavelengths than the original porphyrins. The possible
      enhancement of PDT effects after HepG2 cell incubation with ALA or HPD was
      investigated by irradiating cells successively with red light (lambda = 632 nm)
      and light (lambda = 650 nm)(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8558371
TI  - Protection of plasmid pBR322 DNA by flavonoids against single-stranded breaks
      induced by singlet molecular oxygen.
AB  - Flavonoids, the dominant colouring pigments of plants, as well as the related
      polyphenol tannic acid significantly inhibit single-strand breaks in plasmid
      pBR322 DNA induced by singlet molecular oxygen ((1)O2). This reactive species of
      oxygen was generated in an aqueous buffer system by the thermal dissociation of
      the endoperoxide of 3,3'-(1,4-naphthylene)dipropionate. Among the antioxidants
      examined, myricetin showed the highest protective ability, followed by tannic
      acid, (+)catechin, rutin, fisetin, luteolin and apigenin, when the inhibitory
      abilities were compared at 90 min after incubation. The protective abilities of
      these compounds were both time and concentration dependent. At equimolar
      concentrations (100 microM) the antioxidant effect of myricetin was better than
      that of other known antioxidants such as lipoate, alpha-tocopherol and beta
      carotene. Data, when analysed in relation to the structures of various compounds,
      showed a rough correlation with protective abilities. Owing to the abundance of
      these compounds in our normal diet, they may play significant roles in preventing
      oxidative damage resulting from potentially deleterious (1)O2.

PMID- 8558372
TI  - Progress in pediatric neuropsychology.

PMID- 8558373
TI  - Achievement in children with birth weights less than 750 grams with normal
      cognitive abilities: evidence for specific learning disabilities.
AB  - Examined achievement, behavior, and neuropsychological outcomes at early school
      age in a regional population of children < 750-g birth weight who were
      neurologically intact and who scored in the broad average range on a test of
      cognitive ability. Comparison groups included children of birth weight 750-1,499
      g and children born at full-term. The children < 750 g performed more poorly than
      the higher birth weight groups on tests of math, even after adjusting for group
      differences in cognitive ability. Corresponding group differences were found in
      language, perceptual motor, and attentional skills, but not in behavior outcomes.
      Findings document specific weaknesses in achievement and neuropsychological
      skills in children < 750 g birth weight and support the need for early
      identification and special education interventions.

PMID- 8558374
TI  - Late neuropsychological outcomes in preterm infants of normal IQ: selective
      vulnerability of the visual system.
AB  - Evaluated neuropsychological outcomes in 635 children, ages 7 to 10 years, in
      relation to birth weight group: < or = 1,000 g; 1,001-1,500 g; 1,501-2,500 g, and
      > 2,500 g. The prevalence of low IQ (< 85) was related to birth weight. Among
      children with IQ > 84 (N = 475): (a) Birth weight was unrelated to Verbal IQ,
      Performance IQ, Full-scale IQ, or reading achievement; (b) extremely low birth
      weight (ELBW) children achieved more poorly in mathematics than did other birth
      weight groups (p < .05); (c) ELBW and very low birth weight children performed
      more poorly on the Rey-Osterrieth Complex Figure, a complex visual processing
      task, than did heavier birth weight children (p < .05), but performance on the
      Beery Test of Visuomotor Integration was not related to birth weight. Results are
      consistent with heightened neurobehavioral vulnerability of visual processing to
      preterm birth.

PMID- 8558375
TI  - Assessing the effects of traumatic brain injury on family functioning: conceptual
      and methodological issues.
AB  - Reviewed empirical literature published since 1975 on the effects of pediatric
      traumatic brain injury (TBI) on the family. Few systematic, hypothesis-driven
      investigations of the impact of TBI on family functioning have been conducted.
      However, existing findings indicate that severe TBI can adversely affect families
      and individual family members. Certain factors, such as poor preinjury
      functioning and parental psychological disorder, appear to place families at
      greater risk for long-term disruption. Issues associated with the
      conceptualization of the impact of TBI on various aspects of family functioning
      are discussed and methodological considerations are outlined. Special attention
      is given to novel strategies for studying these complex, multifaceted issues.
      Finally, a framework is proposed for examining the processes of family adaptation
      after pediatric TBI to guide future research directions.

PMID- 8558376
TI  - Neuropsychological deficit and academic performance in children and adolescents
      following traumatic brain injury.
AB  - Evaluated the utility of neuropsychological testing in predicting academic
      outcome in children 1 year following traumatic brain injury (TBI). Fifty-one
      school age children who were admitted to hospital after TBI were assessed with a
      battery of neuropsychological measures at 3 months postinjury. Academic
      achievement was assessed at 3 and 12 months postinjury. The neuropsychological
      battery included intelligence testing and measures of memory, learning, and speed
      of information processing. Academic outcome was assessed in terms of post-TBI
      changes in reading, spelling, and arithmetic; changes in teacher ratings of
      school performance; and change in school placement. According to logistic
      regression analysis, change in placement from regular to special education at 1
      year post-TBI was predicted by injury severity and by neuropsychological
      performance at 3 months post-TBI. Findings suggest that neuropsychological
      testing is useful in identifying children with special educational needs
      subsequent to TBI.

PMID- 8558377
TI  - Family and illness predictors of outcome in pediatric brain tumors.
AB  - Investigated the prediction of cognitive and behavioral outcomes in 63 children
      with heterogenous brain tumors. Hierarchical multiple regression analyses were
      used to determine how family-related variables added to the prediction of
      children's outcome over and above illness measures. The best predictors of
      children's behavior problems and adaptive behavior were family and demographic
      variables, whereas the best predictors of achievement were illness and
      demographic variables. A combination of family and illness variables, however,
      was the best predictor of intellectual functioning. In addition to identifying
      specific predictors of cognitive and behavioral outcome in children with brain
      tumors, these results lend initial support for the inclusion of contextual
      factors such as family stress, maternal coping, number of parents in the home,
      and family SES measures in studies of how disease factors affect outcomes in
      pediatric brain tumor patients.

PMID- 8558378
TI  - Verbal and nonverbal skill discrepancies in children with hydrocephalus: a five
      year longitudinal follow-up.
AB  - Compared verbal and nonverbal skills of 65 children ages 5 to 7 years, with a
      history of shunted hydrocephalus (n = 26), arrested hydrocephalus (n = 11), and
      no hydrocephalus (n = 28), over a 5-year period. Comparison of these skills in 4
      assessments revealed poorer average nonverbal than verbal skills on measures from
      the McCarthy Scales of Children's Abilities, the Wechsler Intelligence Scales for
      Children-Revised (WISC-R), and composites of neuropsychological skills for the
      shunted hydrocephalus group in comparison to the arrested-hydrocephalus and no
      hydrocephalus groups. There were higher rates of significant discrepancies
      between WISC-R Verbal IQ (VIQ) and Performance IQ (PIQ), with PIQ < VIQ in the
      shunted group. However, relatively few children exhibited significant
      discrepancies on multiple test occasions. The poorer performance of the shunted
      hydrocephalus group could not be attributed to motor demands of the nonverbal
      tasks.

PMID- 8558379
TI  - Verbal learning and memory in children with myelomeningocele.
AB  - Examined verbal learning and memory in children with myelomeningocele using the
      California Verbal Learning Test (CVLT). Participants included 41 children with
      myelomeningocele, 8 to 15 years of age, 33 of whom had a history of shunted
      hydrocephalus, and 41 matched, unaffected controls. Children with
      myelomeningocele and shunted hydrocephalus performed worse than controls on the
      CVLT. They recalled as many words as controls on the first learning trial, but
      acquired words more slowly across trials, so that their overall recall was lower.
      Their learning was characterized by a pronounced recency effect. Their delayed
      recall of the original list was worse than controls, but not their recognition.
      Performance of children with myelomeningocele but without shunts was generally
      not significantly different from that of the other two groups, although they did
      demonstrate better long-delay free recall than children with shunts.
      Myelomeningocele is associated with significant retrieval problems when
      accompanied by shunted hydrocephalus.

PMID- 8558380
TI  - Spinal lesion level, shunt status, family relationships, and psychosocial
      adjustment in children and adolescents with spina bifida myelomeningocele.
AB  - Investigated whether family functioning and child psychosocial adjustment were
      associated with spinal lesion level and shunt status in 65 children and
      adolescents with spina bifida myelomeningocele (age range = 8-16). Mothers of
      children with higher lesion levels (i.e., thoracic level) reported more
      attachment to their children, less family conflict, and a greater willingness to
      grant autonomy to their offspring. Such findings support a "marginality"
      interpretation of the data, insofar as the least physically impaired children
      with spina bifida exhibited the greatest family difficulties. Based on maternal
      report, children with shunts performed more poorly in school and exhibited lower
      levels of cognitive competence than children without shunts. Findings are
      discussed in relation to literatures on neuropsychological functioning and
      psychosocial adjustment in children with spina bifida.

PMID- 8558381
TI  - Influence of pH adjustment on microcapsules obtained from complex coacervation of
      gelatin and acacia.
AB  - The coacervation behaviour of commercial grade gelatin and acacia mixtures was
      studied with five different acids to adjust the coacervation pH, i.e. HCl, HNO3,
      H2SO4, acetic acid, and citric acid. The electrical equivalence pH value (EEP) of
      the polymer mixture was determined by means of a streaming current detector
      (SCD). With all acids--except H2SO4--maximum coacervate yield was observed at the
      EEP. Using H2SO4 the EEP was found at a lower pH value than compared with the
      point of maximum coacervate yield. The quantity of coacervate at the EEP was
      significantly reduced in the presence of H2SO4 whereas with all other acids,
      almost no differences were found. The dependence of the coacervate volume on the
      added amount of acid did not change in parallel to the dry coacervate yield and
      there was no coincidence of the maximum coacervate volume and the EEP. The
      barrier properties of the capsule shells of corresponding microcapsules using
      indomethacin as a model drug were examined by dissolution studies. Indomethacin
      microcapsules showed the slowest release rate when the coacervation pH was
      adjusted to the EEP and not to the pH of maximum coacervate yield. As expected
      from the coacervation behaviour, dissolution profiles of the microcapsules were
      quite similar even when different acids were used for pH adjustment.

PMID- 8558382
TI  - Preparation and in vitro dissolution of salbutamol sulphate microcapsules and
      tabletted microcapsules.
AB  - Salbutamol sulphate is a sympathomimetic amine having a rather short plasma half
      life. Aiming to achieve sustained release of this drug through
      microencapsulation, the coacervation method with a 1:1 core-shell ratio was used.
      In vitro release rate experiments were performed on the microcapsules prepared
      using ethyl cellulose as the coating agent and compared to the results of intact
      drug, the tabletted microcapsules and a commercial tablet. The release rate of
      salbutamol sulphate could be controlled through microencapsulation. The time for
      the 50% release of the drug was 15 and 90 min for the tabletted microcapsules and
      microcapsules respectively. The specific surface area of the intact drug was 0.35
      m2/cc while it reduced to 0.06 m2/cc after encapsulation.

PMID- 8558383
TI  - Multiple emulsion-based systems carrying insulin: development and
      characterization.
AB  - An insulin delivery system based on liquid surfactant membranes has been
      developed. The formulation was based on a w/o/w emulsion where an organic
      membrane separated two aqueous phases and the internal aqueous phase contained
      insulin. Sesame and cotton seed oils were used as organic membranes. In order to
      facilitate the transportation of glucose across the organic membrane various
      additives such as calcium stearate, lecithin, cholesterol, hexamine, stearic acid
      and glyceryl tristearate were used. The additives were found to be successful
      carriers for the transportation of glucose to the internal aqueous phase.
      Similarly, viscosity enhancers, e.g. cetostearyl alcohol, in the organic phase
      enhanced the immobilization of insulin. Various parameters affecting the
      stability of the emulsions were established. The developed system was
      characterized for insulin activity and insulin efflux profile.

PMID- 8558384
TI  - Evaluation of an aliphatic polyurethane as a microsphere matrix for sustained
      theophylline delivery.
AB  - In spite of several biomedical applications of polyurethanes, very little
      attention has been focused on these polymers for controlled drug delivery. In
      this study, an aliphatic polyurethane, Tecoflex, was evaluated as a microsphere
      matrix for the controlled release of theophylline. Polyurethane microspheres
      containing theophylline were prepared using a solvent evaporation technique from
      a dichloromethane solution of the polymer containing the drug. A dilute solution
      of poly(vinyl alcohol) served as the dispersion medium. Microspheres of good
      spherical geometry having theophylline content of 35% could be prepared by the
      technique. The release of the drug from the microspheres was examined in
      simulated gastric and intestinal fluids at 37 degrees C. While a large burst
      effect was observed in gastric fluid, in the intestinal fluid a close to zero
      order release was seen. Attempts were made to modulate the release by
      incorporating poly(ethylene glycol) in the matrix and also coating the spheres
      with paraffin wax. Preliminary data indicate that polyurethanes could be
      interesting matrices for controlled drug delivery.

PMID- 8558385
TI  - Production of water-containing polymer microcapsules by the complex
      emulsion/solvent evaporation technique. Effect of process variables on the
      microcapsule size distribution.
AB  - The complex emulsion/solvent evaporation technique was employed for the
      production of water-containing polymer microcapsules. The inner phase of the
      microcapsules consisted of an aqueous solution of gelatin. Several polymers (e.g.
      poly(styrene), poly(methyl methacrylate), ethyl cellulose, poly(vinyl chloride))
      were utilized as wall-forming materials and the effect of the polymer type on the
      size and the surface characteristics of the microcapsules was experimentally
      investigated. The size of the microcapsules was strongly affected by the
      conditions applied during the formation of both simple (w/o) and complex (w/o)/w
      emulsions. Poly(styrene) microcapsules with a mean Sauter diameter in the range
      of 4-12 microns were prepared by varying the rate of agitation (1500-4000 rpm)
      and the concentration of stabilizer (potassium oleate, 0.1-1.5% w/v) used in the
      formation of the (w/o)/w emulsion. High stabilizer concentrations and agitation
      rates resulted in a significant reduction of the mean size of the complex
      droplets and in a simultaneous increase of the breadth of the capsule size
      distribution.

PMID- 8558386
TI  - Study of a microencapsulation process of a virucide agent by a solvent
      evaporation technique.
AB  - A highly water-soluble virucide agent was microencapsulated by a water/oil/water
      emulsification-solvent evaporation method. An aqueous drug solution was
      emulsified into a solution of polymer in methylene chloride, followed by
      emulsification of the primary emulsion in an external aqueous phase.
      Microcapsules were formed after solvent evaporation, the solidification of the
      microcapsule walls was followed by an optical method. The influence of stirring
      speed was analysed to find the optimal hydrodynamic conditions with respect to
      the process yield, corresponding to the weight of obtained microcapsules per
      litre of water/oil/water emulsion, the initial virucide agent content and the
      drug release kinetics. The optimal conditions were obtained for the complete
      suspension speed. The improvement of the microencapsulation process was attempted
      by increasing the concentration of the primary emulsion and by the reuse of the
      external aqueous phase after removal of the microcapsules.

PMID- 8558387
TI  - Preparation and in-vitro evaluation of sustained-release metoclopramide
      hydrochloride microspheres.
AB  - Sustained-release metoclopramide microspheres were successfully prepared using
      cellulose propionate polymer at 1:2 drug to polymer ratio employing solvent
      evaporation technique and using acetone as the polymer solvent. The prepared
      microspheres at three stirring speeds were characterized with regard to their
      drug content, particle size distribution, surface topography using SEM and their
      release profiles at two different pHs at 37 degrees C. The surface of all samples
      was smooth with very few irregular elevations or depressions. The average
      particle size decreases as the rotational speed increases and was found to be
      1320, 774 and 345 microns at 600, 900 and 1200 rpm, respectively. The average %
      drug entrapped was found to be 90.5, 100.1 and 60.0% at 600, 900 and 1200 rpm,
      respectively. Small differences in the release rate were observed due to
      different rotation speeds with an apparent lower dissolution for batches produced
      at 1200 rpm probably due to the properties of the coat. The effect of storage
      under accelerated conditions for 10 weeks on the release characteristics of these
      microspheres was also studied. The release properties of the microspheres did not
      change after storing them at 40 degrees C/80% relative humidity for 10 weeks.

PMID- 8558388
TI  - Influence of membrane components on the stability and drug release properties of
      reverse phase evaporation vesicles (REVs): light sensitive all-trans retinal,
      negatively charged phospholipid dicetylphosphate and cholesterol.
AB  - Incorporation of a negatively charged phospholipid, dicetylphosphate, initially
      increased encapsulation efficiency (from 12 to 24%) but beyond 5% (molar) a
      detrimental effect was observed. Rate of drug release from REVs was, for most
      cases, found to be bi-phasic implying partitioning between the lipid bilayer and
      the aqueous compartment. It was not possible to prepare liposomes with more than
      1% (molar) all-trans retinal (ATR) as a membrane component. When ATR was reduced
      to 0.5% (molar), encapsulation efficiency increased to 7.76%. Upon exposure to
      long wave UV (365 nm), release from ATR containing REVs was increased and this
      was attributed to the formation of 13-cis isomer as indicated by HPLC and UV
      spectroscopy data.

PMID- 8558389
TI  - Frequency of self-reported medical conditions in periodontal patients.
AB  - Assessing the medical history of patients before any treatment is provided is an
      essential aspect of the periodontist's responsibility. A patient's compromised
      medical state could alter the response to periodontal treatment or worse,
      contribute to a crisis situation that may prove harmful to his or her well-being.
      This study examines the frequency of medical conditions in periodontal patients
      utilizing a self-administered health questionnaire succeeded by directly
      interviewing the patient for validity. Health histories were taken from 590
      periodontal patients in an outpatient setting; 52.5% of these patients reported a
      positive finding in their medical history, with drug allergies and cardiovascular
      disorders being by far the most frequently found conditions. The frequency of
      medical conditions increased with increasing age. Thorough evaluation of a
      patient's health history is a mandatory first step in the treatment process.

PMID- 8558390
TI  - Familial gingival fibromatosis with unusual histologic findings.
AB  - This article describes the occurrence of numerous calcifications, amyloid
      deposits, and islands of odontogenic epithelium in the gingiva of 3 siblings with
      familial gingival fibromatosis. These microscopic features have not been reported
      previously in patients with this condition.

PMID- 8558391
TI  - Re: Demineralized freeze-dried and autologous bone as aids to healing (J
      Periodontol 1994; 64; 1128-1133)

PMID- 8558392
TI  - Re: Post-rhizotomy periodontal atrophy (J Periodontol 1995; 66:301-302)

PMID- 8558393
TI  - Clinical significance of bacterial resistance to tetracyclines in the treatment
      of periodontal diseases.
AB  - Tetracyclines are frequently employed during the treatment of clinical infections
      in medicine and dentistry, however, emergence of resistant bacterial strains has
      decreased the utility of these drugs. Accordingly, there is concern that
      indiscriminant administration of tetracyclines during periodontal therapy will
      further contribute to the development of additional resistant microorganisms
      which can complicate infectious disease therapy. This review paper briefly
      discusses the utility of tetracyclines as an antimicrobial agent in the treatment
      of periodontal diseases. It then focuses on the clinical significance of
      bacterial resistance to tetracyclines. Patterns of resistance that may be
      associated with the following scenarios are addressed: short- and long-term
      antibiotic therapy, individuals with a history of prior tetracycline therapy,
      patients with refractory periodontitis, and following controlled local drug
      delivery. It appears that selection and development of bacterial resistant
      strains is an inevitable consequence of antibiotic therapy. Nevertheless, prudent
      administration of tetracyclines may help delay or prevent the emergence of
      resistant microorganisms.

PMID- 8558394
TI  - Formation of normal gingival epithelial phenotypes around osseo-integrated oral
      implants in humans.
AB  - The oral, oral sulcular, and junctional epithelia of the natural gingiva each
      possess distinct patterns of differentiation that are demonstrable both
      ultrastructurally and by their individual patterns of macromolecular synthesis.
      The supracrestal tissues reformed around oral implants structurally resemble
      those of natural gingiva but little is known about phenotype changes occurring in
      the epithelia. To investigate whether peri-implant epithelia acquire similar
      patterns of differentiation to those of natural gingiva, biopsies from the
      supracrestal regions of five oral implants were examined by immunofluorescent
      methods using a panel of monoclonal antibodies with specificities for individual
      cytokeratins and ICAM-1, macromolecules which act as markers of the three
      gingival epithelial phenotypes. The observed staining patterns indicated the
      formation of oral, oral sulcular, and junctional epithelia which were
      phenotypically indistinguishable from those of natural gingival epithelia. This
      degree of reprogramming of epithelial gene expression is a surprising observation
      and the potential mechanisms leading to the development of those new epithelial
      phenotypes are discussed in the context of what is known about the development of
      natural gingiva, in terms of the possible effects of inflammation, and in
      relation to the known connective tissue influences on epithelial differentiation.

PMID- 8558395
TI  - An in vitro investigation of the role of high molecular weight human salivary
      sulphated glycoprotein in periodontal wound healing.
AB  - High molecular weight human salivary sulphated glycoprotein (SGP) inhibits
      attachment of fibroblasts to cementum in vitro and thus may enhance periodontal
      wound healing by repair with long junctional epithelium. However, competitive
      inhibition by serum constituents might prevent adequate binding of SGP for this
      effect to occur in vivo. The primary aim of this study was to investigate the co
      adsorption in vitro, of SGP, fibronectin (FN), and albumin (ALB) to synthetic
      hydroxyapatite (HA) from solutions of SGP/FN (62.5/2 micrograms/mL respectively),
      or SGP/FN/ALB (62.5/2/4 micrograms/mL), or from individual solutions of the
      agents as controls: Desorption of SGP and FN was studied by preabsorbing HA with
      SGP or FN and subsequently exposing it to the other agent, or to buffer only as
      control. Adsorbates were assayed after incubation periods of up to 26 hours using
      specific ELISAs. SGP displaced previously adsorbed FN after 3 hours and
      significantly inhibited adsorption of FN and ALB compared with controls. Neither
      FN or ALB had a significant effect on SGP adsorption. These results are
      consistent with the possibility that salivary adsorption to cementum during
      surgery might interfere with repopulation of the root by connective tissue cells
      and thus contribute to wound healing by repair rather than regeneration. Separate
      studies taken to validate the ELISA used for SGP determination showed that HA
      bound SGP contained all constituents of native SGP as revealed by SDS-PAGE and
      that ion exchange chromatography of SGP gave 6 fractions (I through VI), of which
      only the most ionic (VI) was able to inhibit cell attachment in vitro.

PMID- 8558396
TI  - A scanning electron microscope study comparing the effectiveness of different
      types of sharpening stones and curets.
AB  - The effects of various types of sharpening stones on standard carbon steel Gracey
      type curets, and the influence of the sharpened curets on periodontally involved
      root surfaces, during in vitro scaling and root planing, was evaluated by means
      of scanning electron microscopy (SEM). Six different sharpening stones of varying
      texture, two of aluminum oxide, two India, and two Arkansas stones were assigned
      to sharpen six groups of 10 curets each. The curets were first examined under SEM
      and photographed and all exhibited edge irregularities. They were then sharpened
      with the different stones and again examined and photographed using SEM. The
      sharpness of each instrument was graded, related to the type of stone used, and
      the data compared statistically. A positive correlation was found between the
      texture of stone used and the surface sharpness it produced on the cutting edge
      of the instrument. The curets were then used to root plane the root surfaces on
      periodontally involved, extracted teeth. Replicas of the root surfaces were
      examined with SEM before and after removal of the smear layer with 10% EDTA. The
      planed and cleaned root surfaces revealed the effects of the sharpened
      instruments, with the relative surface roughness of the instrument being imparted
      to the tooth surface. The curets sharpened with finger grit stones produced
      smoother surfaces than those sharpened with the rough or coarse grit stone. It
      may be concluded that the sharpness of curets is related to the type of
      sharpening stone used and in turn to the smoothness of the planned root.

PMID- 8558397
TI  - The effect of an antiseptic mouthrinse on implant maintenance: plaque and peri
      implant gingival tissues.
AB  - The purpose of this controlled double-blind, parallel, randomized clinical study
      was to determine the effect of antiseptic mouthrinse on parameters important to
      dental implant maintenance. Plaque, peri-implant gingivitis, gingival bleeding,
      probing depth, and attachment level were assessed over a 3-month test period.
      Twenty healthy adult patients each of whom had at least two dental implants, a
      modified gingival index > 1.5, and a modified Quigley-Hein plaque index score >
      1.7 were enrolled into the study. After a thorough oral prophylaxis, patients
      were randomly assigned to either the antiseptic mouthrinse or a 5% hydroalcohol
      placebo mouthrinse group and instructed to rinse twice daily for 30 seconds with
      20 ml of their assigned mouthrinse as an adjunct to their usual oral hygiene
      procedures. The baseline examination included plaque index, gingival index,
      bleeding index, probing depth measurement, and attachment level measurements. The
      plaque and gingival indices were rescored at 1, 2, and 3 months. Probing depths,
      attachment levels, and bleeding index were determined again at 3 months only. At
      the end of 3 months, the antiseptic mouthrinse group had statistically
      significant reductions in plaque index, gingival index, and bleeding index
      compared to the placebo group. There were no significant differences between
      groups in probing depth or attachment level. The results of this clinical study
      indicate that twice daily use of an antiseptic mouthrinse may provide benefits in
      the maintenance of dental implants.

PMID- 8558398
TI  - The influence of insulin-like growth factor (IGF) on C19 steroid conversions by
      human gingiva and in cultured gingival fibroblasts.
AB  - The metabolic conversion of 14C-testosterone by human gingival tissue in response
      to IGF was studied. Androgen metabolic studies were also performed in 5 to 7 cell
      lines of cultured gingival fibroblasts, using 14C-testosterone and 14C-4
      androstenedione as initial substrates. Duplicate incubations of gingival tissue
      were performed after establishing the wet weight, in Eagle's MEM + 10% FCS and
      optimal stimulatory concentrations of IGF for 24 hours. Similar incubations were
      performed in duplicate with cell-lines of gingival fibroblasts, control/IGF, and
      14C-testosterone/14C-4-androstenedione. At the end of the incubation period, the
      radioactive metabolites were extracted, evaporated, subjected to thin layer
      chromatography for their separation, and quantified by scanning in a Berthold's
      linear analyzer. With the gingival tissue samples, IGF caused a 4-fold increase
      in 5 alpha-dihydrotestosterone (DHT) synthesis (n = 5; P < 0.1, Wilcoxon signed
      rank test for paired observations) and a 3.5-fold increase in 4-androstenedione
      formation (n = 5; P < 0.1) from 14C-testosterone. When similar incubations were
      performed with cell-lines of fibroblasts and 14C-testosterone, average values of
      duplicate incubations showed a 2.5-fold increase in DHT synthesis in response to
      IGF (n = 7; P < 0.002) and a 2.3-fold increase in 4-androstenedione formation (n
      = 7; P < 0.002). With 14C-4-androstenedione as substrate, IGF stimulated a 2.7
      fold increase in DHT synthesis (n = 5; P < 0.1) compared with controls and a 1.8
      fold increase in testosterone formation (n = 5; P < 0.1). Since both DHT and IGF
      are implicated in protein turnover by fibroblasts, significant stimulation of DHT
      synthesis by IGF in gingiva and cultured fibroblasts is suggestive of a possible
      mechanism for mediating inflammatory repair via the androgen metabolic pathway.

PMID- 8558399
TI  - 10-year periodontal response to resin bonded bridges.
AB  - The purpose of this study was to evaluate the long-term (10 years +/- 15 months)
      periodontal response to resin bonded bridges (RBRs). A total of 103 patients who
      had RBRs bonded between 1980 and 1984 were recalled. Periodontal evaluations were
      made by two clinicians for all abutment teeth and for selected control teeth with
      intact, non-restored lingual surfaces. Periodontal indices consisted of: plaque
      index (PI), gingival index (GI), gingival recession, probing depth, and loss of
      attachment. Paired t tests indicated no significant difference in overall GI
      between experimental and control sites, but a significant difference in PI and
      probing depth with experimental sites (abutment teeth) showing higher PI and
      greater probing depths. Significant differences were found in overall recession
      and attachment loss, again with more recession and attachment loss observed on
      the abutment teeth as compared to the controls. Site specific analyses for PI,
      probing, and loss of attachment showed small but significant differences between
      experimental and control teeth in 15 of 21 sites. Although these findings may be
      statistically significant, the clinical impact for resin bonded restorations
      functioning for over 10 years is minimal and is comparable to periodontal
      response to other types of restorations.

PMID- 8558400
TI  - Slow release of tetracycline hydrochloride from a cellulose membrane used in
      guided tissue regeneration.
AB  - The objective of this study was to evaluate if the biologic membrane utilized for
      GTR can be impregnated by tetracycline hydrochloride and if the chemotherapeutic
      agent, once impregnated, can be released in minimal inhibitory concentrations for
      a period compatible with clinical application. Initially, an in vitro study was
      done with cellulose membranes cut in pieces measuring 9 cm2. A volume of 100
      microliters containing a 72,000 micrograms/ml solution of tetracycline was
      dispensed onto each fragment, and dried for 70 minutes at 37 degrees C. Four
      pieces measuring 0.5 cm2 were cut from different points of the 9 cm2 membrane
      (presumably, containing 400 micrograms of tetracycline), placed in test tubes
      containing 4 ml of sterile deionized water, and agitated for 2 minutes. A
      standard curve was made from known concentrations of tetracycline and compared to
      10 microliters of the test solutions obtained by the elution of the 0.5 cm2
      fragments. The concentrations were determined through the bioassay technique in 3
      duplicate experiments. The samples recovered from the membrane fragments had a
      mean of 101 micrograms/ml of tetracycline liberated, demonstrating that the
      membrane was impregnated homogeneously by the chemotherapeutic agent. In a second
      phase, an in vivo study was carried out to determine the length of time the drug
      was liberated from the membranes and at which concentrations, in the presence of
      an inflammatory process. Fourteen 0.5 cm2 fragments containing 400 micrograms of
      tetracycline were placed in 14 polypropylene chambers containing 200 microliters
      of thioglycolate medium. The chambers were implanted in the peritoneal cavities
      of 14 mice, one chamber per animal, and left in from 1 to 14 days. They were then
      removed and the concentrations of tetracycline determined from 20 microliters
      samples using a bioassay. The results showed that the antibiotic was released
      slowly from the 1st through the 12th day in decreasing concentrations that varied
      from 218 to 20.8 micrograms/ml. The impregnated cellulose membrane can probably
      be used in GTR acting as a membrane and as a slow-release device, liberating the
      chemotherapeutic agent in concentrations high enough to eliminate
      periodontopathic microorganisms.

PMID- 8558401
TI  - Reproducibility and validity of furcation measurements as related to class of
      furcation invasion.
AB  - The furcation involvement of 200 molars in 50 patients suffering from advanced
      periodontitis was investigated. Presurgically, the horizontal probing attachment
      levels (CAL-H) within the furcations of 4 molars per patient was assessed twice
      within 14 days. Within a subset of 11 patients duplicate measurements of clinical
      probing depths (PD) and vertical clinical attachment levels (CAL-V) at the same
      molars were performed. To determine the measurement error of CAL-H, PD and CAL-V,
      respectively, the standard deviation of single measurements were calculated. The
      CAL-H measurements were repeated intrasurgically and compared with presurgical
      assessments of furcation measurements. The overall standard deviation of single
      measurements was 0.759 mm. For Class 0, I, and II furcations, the standard
      deviations were 0.879 mm, 0.664 mm, 0.682 mm, respectively. The standard
      deviation of PD single measurements and CAL-V single measurements varied from
      0.393 mm to 0.993 mm (PD) and from 0.555 mm to 1.161 mm (CAL-V), respectively.
      The agreement of replicate measurements of furcation degrees was moderate for
      furcation locations which showed a CAL-H < or = 3 mm and a CAL-H > 3 mm,
      respectively (weighted kappa-coefficients 0.500 and 0.691). At sites with
      furcation involvement Class O and II there was no statistically significant
      difference between presurgical and intrasurgical measurements. At sites with
      Class I furcations there was a statistically significant mean difference of 0.255
      mm between presurgically and intrasurgically assessed CAL-H. There was no
      statistically significant difference between furcation classes as assessed
      presurgically and intrasurgically (chi 2 between 1.9 and 4.4).

PMID- 8558402
TI  - Necrotizing ulcerative gingivitis, periodontitis, and stomatitis: clinical
      staging and predisposing factors.
AB  - Necrotizing ulcerative gingivitis (NUG), necrotizing ulcerative periodontitis
      (NUP), and necrotizing stomatitis (NS), collectively termed necrotizing
      gingivostomatitis (NG), represent a dramatic, but rare oral infection associated
      with diminished systemic resistance, including HIV infection. Over a 5-year
      period, 68 consecutive NG patients from a population with known HIV status were
      evaluated and treated. Lesions were staged (modified Pindborg), and clinical
      findings and predictor variables were compared to 68 random control subjects
      without NG. Most cases (52%) were stage 1, with necrosis of the tip of the
      interdental papilla only; 19% were stage 2, with the entire papilla affected; 22%
      had necrosis of marginal (stage 3) or attached gingiva (stage 4); and 7% were
      more advanced, with mucosal necrosis or bone exposure. Attachment loss was a
      feature of stage 2 or greater NG. Beside HIV infection, significant predisposing
      factors included poor oral hygiene, unusual life stress, inadequate sleep,
      Caucasian race, age 18 to 21 years, and recent illness. Ten of 68 NG patients
      were HIV-positive. These patients were older than seronegative patients, less
      likely to be Caucasian, and maintained better oral hygiene and sleep. HIV
      positive NG cases were clinically indistinguishable from HIV-negative cases in
      this series.

PMID- 8558403
TI  - The effect of bisphosphonate on alveolar bone resorption following mucoperiosteal
      flap surgery in the mandible of rats.
AB  - Following elevation of a full thickness flap a transient burst of regional
      remodeling occurs. This phenomenon is termed in orthopedic surgery as regional
      accelerated phenomenon (RAP), beginning with accelerated resorption activity
      followed by a slow process of bone regeneration. Recently we have demonstrated
      that a mucoperiosteal surgical flap of rat mandible is producing a typical RAP
      process. Bisphosphonates are synthetic compounds that are taken up preferentially
      by the skeleton and suppress osteoclast-mediated bone resorption by a mechanism
      that is not yet fully understood. Amino bisphosphonate has been shown to inhibit
      active bone resorption without interfering with bone formation. In this study we
      evaluated the effect of amino bisphosphonate on bone resorption associated with a
      mucoperiosteal flap used as a resorptive model. We compared the effect of amino
      bisphosphonate in rats using IV administration with topical application at 3 dose
      levels. The results show that topical application of all 3 doses (0.15, 0.75, and
      1.5 mg/ml) had no inhibiting effect on bone resorption after surgery, while IV
      administration at 0.5 mg/kg body weight significantly reduced the bone
      resorption. Interestingly, in the non-operated side, amino bisphosphonate
      increased mineral density.

PMID- 8558404
TI  - 5th International Symposium on Drug Analysis. Leuven, Belgium, 12-15 September
      1995. Abstracts.

PMID- 8558405
TI  - Motivational predictors of weight loss and weight-loss maintenance.
AB  - Self-determination theory proposes that behavior change will occur and persist if
      it is autonomously motivated. Autonomous motivation for a behavior is theorized
      to be a function both of individual differences in the autonomy orientation from
      the General Causality Orientations Scale and of the degree of autonomy
      supportiveness of relevant social contexts. We tested the theory with 128
      patients in a 6-month, very-low-calorie weight-loss program with a 23-month
      follow-up. Analyses confirmed the predictions that (a) participants whose
      motivation for weight loss was more autonomous would attend the program more
      regularly, lose more weight during the program, and evidence greater maintained
      weight loss at follow-up, and (b) participants' autonomous motivation for weight
      loss would be predicted both by their autonomy orientation and by the perceived
      autonomy supportiveness of the interpersonal climate created by the health-care
      staff.

PMID- 8558406
TI  - Genetic and environmental structure of the Tridimensional Personality
      Questionnaire: three or four temperament dimensions?
AB  - Previous phenotypic factor analyses suggest that C. R. Cloninger's Tridimensional
      Personality Questionnaire (TPQ; 1987c) assesses 4 rather than 3 temperament
      dimensions. The purpose of this study was to determine whether Cloninger's
      revised 4-factor model showed incremental validity over his original model and to
      investigate the convergent and discriminant validity of Cloninger's dimensions in
      comparison to the personality dimensions proposed by H. J. Eysenck (1981) and J.
      A. Gray (1970). The sample included 2,420 women and 870 men (aged 50-96) from a
      volunteer population-based sample of twins. Joint phenotypic factor analyses
      supported Cloninger's 4-dimensional temperament model. A 4-dimensional genetical
      factor structure was also confirmed in genetic analyses of the TPQ higher order
      dimensions in women. For men only 3 genetic factors were necessary to explain the
      genetic variance among the TPQ dimensions.

PMID- 8558407
TI  - Resilient, overcontrolled, and undercontrolled boys: three replicable personality
      types.
AB  - Three replicable personality types were identified in a sample of 300 adolescent
      boys and shown to generalize across African Americans and Caucasians. The types
      had conceptually coherent relations with the Big Five dimensions, ego resiliency,
      and ego control, and converged with three of the types identified by J. Block
      (1971). The behavioral implications of the types were explored using several
      independent data sources. Resilients were intelligent, successful in school,
      unlikely to be delinquents, and relatively free of psychopathology;
      Overcontrollers shared some of these characteristics but were also prone to
      internalizing problems; and Undercontrollers showed a general pattern of
      academic, behavioral, and emotional problems. This research demonstrates that
      replicable and generalizable personality types can be identified empirically, and
      that the unique constellation of traits defining an individual has important
      consequences for a wide range of outcomes.

PMID- 8558408
TI  - A prisoner's dilemma experiment on cooperation with people and human-like
      computers.
AB  - The authors investigated basic properties of social exchange and interaction with
      technology in an experiment on cooperation with a human-like computer partner or
      a real human partner. Talking with a computer partner may trigger social identity
      feelings or commitment norms. Participants played a prisoner's dilemma game with
      a confederate or a computer partner. Discussion, inducements to make promises,
      and partner cooperation varied across trials. On Trial 1, after discussion, most
      participants proposed cooperation. They kept their promises as much with a text
      only computer as with a person, but less with a more human-like computer.
      Cooperation dropped sharply when any partner avoided discussion. The strong
      impact of discussion fits a social contract explanation of cooperation following
      discussion. Participants broke their promises to a computer more than to a
      person, however, indicating that people make heterogeneous commitments.

PMID- 8558409
TI  - Cross-cultural generalizability of personality dimensions: relating indigenous
      and imported dimensions in two cultures.
AB  - The cross-cultural generalizability of personality dimensions was investigated by
      (a) identifying indigenous Philippine dimensions, (b) testing the cross-cultural
      replicability of the NEO 5-factor model (P. T. Costa & R.R. McCrae, 1992), and
      (c) relating Philippine and Western dimensions in Philippine and U.S. samples of
      college students. Filipino self-ratings (N = 536) on indigenous items were factor
      analyzed, and 6 Philippine dimensions were obtained. Conclusions about the
      replicability of the 5-factor model in the Philippines (N = 432) depended on
      whether exploratory, Procrustes, or confirmatory factor methods were used. In
      regression and joint factor analyses, moderate to strong associations were found
      between the Philippine dimensions and (a) dimensions from the 5-factor model in
      both Philippine (N = 387) and U.S. (N = 610) samples, and (b) the Tellegen model
      (A. Tellegen, 1985; A. Tellegen & N.G. Waller, in press) in a U.S. sample (N =
      603).

PMID- 8558410
TI  - [Intravascular ultrasound scanning assessment of plaque distribution in the left
      anterior descending coronary artery just distal to the bifurcation].
AB  - Coronary plaque has a distinct spatial distribution with the peak incidence on
      the outer wall around the bifurcation of the left main coronary artery.
      Intravascular ultrasound scanning was used to evaluate the distribution of the
      plaque in the proximal site of the left anterior descending coronary artery in 16
      patients. Coronary angiography showed the examined sites were normal in all
      patients. A cross-sectional coronary scan was recorded in the left anterior
      descending coronary artery just distal to the bifurcation using a 4.3 Fr, 30 MHz
      intravascular ultrasound catheter. The thickness of the plaque was measured at 0,
      90, 180, and 270 degrees, where 0 degree indicates the left circumflex coronary
      artery branching direction. The scan was divided into four areas of 90 degrees
      and labeled 1 to 4 in the counterclockwise direction (site 1 was the left
      circumflex coronary artery branching direction). The thickness and area of the
      plaque were measured in each site. The percentage plaque fraction was calculated
      as (plaque area in each site)/(plaque area of all) x 100. In 15 (94%) of the 16
      patients, images of crescent shaped plaques were obtained. The mean thicknesses
      of the plaque at sites 1-4 were 0.25 +/- 0.07 mm, 0.46 +/- 0.21 mm, 0.82 +/- 0.19
      mm, and 0.42 +/- 0.23 mm, respectively. The mean percentage plaque fractions were
      7.9 +/- 3.6% (site 1), 18.1 +/- 7.2% (site 2), 55.0 +/- 8.1% (site 3), 18.7 +/-
      6.9% (site 4), respectively. In site 3, opposite to the left circumflex coronary
      artery branching, the thickness and percentage plaque fraction were significantly
      greater than the remaining three sites (p < 0.001). In vivo intravascular
      ultrasound scanning revealed that coronary plaque in angiographically normal left
      anterior descending coronary artery just distal to the bifurcation has a distinct
      distribution with a peak incidence opposite to the left circumflex coronary
      artery branching.

PMID- 8558411
TI  - [Comparison of exercise-stress single photon emission computed tomography with
      thallium-201 reinjection and postextrasystolic potentiation to assess myocardial
      viability in patients with myocardial infarction].
AB  - Myocardial viability was examined in 20 patients with myocardial infarction 24 +/
      3 (mean +/- standard deviation) days after onset. Postextrasystolic potentiation
      (PESP) was measured by left ventriculography and thallium-201 (Tl) single photon
      emission computed tomography (SPECT) redistribution was assessed after stress
      loading and reinjection of Tl. The results were compared with the improvement of
      left ventricular segmental wall motion after coronary revascularization which was
      performed successfully in all patients. The uptake of Tl was impaired initially
      in 41 segments, classified into three groups: normal group, 13 segments with
      smooth reversion to normal; new fill-in group, 15 segments with a new fill-in
      after reinjection of Tl; no fill-in group, 13 segments with no fill-in after
      reinjection. When evaluated by the PESP before coronary revascularization,
      segmental wall motion was significantly augmented in all segments in the normal
      group and new fill-in group (p < 0.001), but not in the no fill-in group. After
      coronary revascularization, left ventriculography revealed that segmental wall
      motion was significantly improved in normal group and new fill-in group, but not
      in the no fill-in group except for mild improvement in five segments. The
      sensitivity and specificity of PESP (90% and 93%) and Tl SPECT (80% and 100%) for
      improvement of segmental wall motion after the coronary revascularization were
      very high, with the accuracy of either method attaining 87%. This result
      indicates that both Tl SPECT and PESP are useful for detecting viable myocardium
      in patients with recent myocardial infarction.

PMID- 8558412
TI  - [Effects of weight training on muscle strength and exercise capacity in patients
      after myocardial infarction].
AB  - The effect of combined aerobic and weight training on indexes of muscle strength
      and exercise capacity was investigated in 59 patients after myocardial
      infarction. Subjects were randomly assigned into three groups: group I performing
      combined aerobic and weight training (n = 22), group II performing ordinary
      aerobic training alone (n = 19) and group III not performing physical training (n
      = 18). Before and after the training, isokinetic knee extension strength was
      measured and cardiopulmonary exercise testing was performed. Physical training
      was prescribed for 8 weeks. Weight training of knee extensors was performed at
      60% of 1 repetition maximum and aerobic training was prescribed at the heart rate
      of anaerobic threshold (AT) level. After 8 weeks, the increase of isokinetic knee
      extension strength was significantly greater in group I (26 +/- 14%) than group
      II (6 +/- 8%) and III (4 +/- 8%). Increases in peak VO2, exercise time, AT and
      peak O2 pulse were greater in groups I and II than group III. Furthermore,
      increase of exercise time was greater in group I (25 +/- 14%) than group II (16
      +/- 9%). The rating of perceived exertion in submaximal exercise decreased
      significantly only for group I. In patients with myocardial infarction, combined
      aerobic and weight training is a more effective method for increasing muscle
      strength and exercise capacity than only ordinary aerobic training.

PMID- 8558413
TI  - [Identification of deep septal ventricular tachycardia substrates from epicardial
      breakthrough characteristics].
AB  - This study aimed to elucidate the relationship between the epicardial activation
      pattern and the site of origin of the ventricular tachycardia (VT) occurring from
      the interventricular septum, and to find epicardial breakthrough characteristics
      identifying VT substrates. Seven patients undergoing intraoperative mapping
      including right ventricular endocardial mapping were studied. Thirteen septal
      VTs, which were defined as VTs in which both right and left ventricular
      endocardial breakthroughs were on the septal aspect, were induced. The VT site of
      origin was identified from the site and timing of right and left septal
      endocardial breakthroughs. All VTs were classified into three groups according to
      the site of epicardial breakthrough: type A, epicardial breakthrough in the
      anterior interventricular area; type F, epicardial breakthrough in the right
      ventricular free wall; type P, epicardial breakthrough in the posterior
      interventricular area. All type F VTs had a right ventricular endocardial
      breakthrough in the anterior septum and preceded the left ventricular endocardial
      breakthrough, thereby indicating right anterior septal origin. In the types A and
      P, both the right and left endocardial breakthroughs were localized in consistent
      (anterior and posterior, respectively) halves of the septum, but their relative
      timing was inconstant. This result suggests that epicardial mapping, and even
      noninvasive methods like body surface mapping, can identify the site of origin of
      the septal VTs, especially when the epicardial breakthrough occurs in the right
      ventricular free wall.

PMID- 8558414
TI  - New index of combined systolic and diastolic myocardial performance: a simple and
      reproducible measure of cardiac function--a study in normals and dilated
      cardiomyopathy.
AB  - BACKGROUND: Because systolic and diastolic dysfunction frequently coexist, it is
      hypothesized that a combined measure of left ventricular chamber performance may
      be more reflective of overall cardiac dysfunction than systolic or diastolic
      measures alone. METHODS Study patients consisted of 170 subjects: 70 normals, 47
      patients with severe dilated cardiomyopathy in NYHA class III-IV awaiting cardiac
      transplantation and 53 patients with idiopathic dilated cardiomyopathy of
      intermediate severity [NYHA class II, ejection fractions (EF) 30-50%]. EF, stroke
      volume and cardiac indexes were measured using conventional echo-Doppler methods.
      Pre-ejection period/ejection time (PEP/ET), isovolumetric relaxation time (IRT),
      isovolumetric contraction time/ET (ICT/ET) were also measured. A new derived
      index of myocardial performance: (ICT+IRT)/ET, was obtained by subtracting ET
      from the interval between cessation and onset of the mitral inflow velocity to
      give the sum of ICT and IRT. RESULTS The index was easily measured, reproducible,
      and had a narrow range in normals. The mean value of the index was significantly
      different between normal, intermediate and pre-transplant subjects (0.39 +/-
      0.05, 0.59 +/- 0.10 and 1.06 +/- 0.24, respectively, p < 0.001 for all
      comparisons). The degree of inter-group overlap was smaller for the index
      compared to PEP/ET, ICT/ET and other parameters. Within functional groups, the
      value of the index did not appear to be related to heart rate, mean arterial
      pressure and the degree of mitral regurgitation. CONCLUSION (ICT+IRT)/ET is a
      conceptually new, simple and reproducible Doppler index of combined systolic and
      diastolic myocardial performance in patients with primary myocardial systolic
      dysfunction.

PMID- 8558415
TI  - [Dobutamine stress echocardiography in the diagnosis of myocardial ischemia in
      patients with implanted pacemakers: report of two cases].
AB  - Dobutamine stress echocardiography was used in the diagnosis of myocardial
      ischemia in patients with implanted VVI pacemakers. A 69-year-old woman received
      a pacemaker for Mobitz II type AV block in October 1992. She had suffered from
      chest pain during effort since January 1993 and underwent dobutamine stress
      echocardiography in April 1993. Although the electrocardiogram failed to identify
      ischemia because of the pacemaker rhythm, ischemia of the anterior wall was
      revealed as a worsening of the wall motion on the echocardiogram. The coronary
      angiogram showed 99% stenosis of the left descending artery. A direct coronary
      atherectomy was performed on the lesion. A 68-year-old man received a pacemaker
      for sick sinus syndrome in August 1993. He had suffered from chest oppression
      during effort since May 1992 and underwent dobutamine stress echocardiography in
      October 1993. Spontaneous rhythm appeared with dobutamine infusion, but the
      electrocardiogram could not demonstrate ischemia because of incomparability with
      the rhythm at rest. Echocardiography detected a new wall motion abnormality of
      the inferior wall caused by dobutamine. The coronary angiogram showed 90%
      stenosis of the right coronary artery. PTCA was performed on the lesion.
      Dobutamine stress echocardiography is useful for the diagnosis of myocardial
      ischemia in patients with implanted pacemakers.

PMID- 8558416
TI  - A dose-response study of neuroprotection using the AMPA antagonist NBQX in rat
      focal cerebral ischemia.
AB  - AMPA antagonists have been shown to be remarkably neuroprotective in models of
      global ischemia, but the data in focal ischemia remain controversial. We,
      therefore, studied the dose-response characteristics and the time window of
      efficacy of the AMPA antagonist NBQX in a rat model of permanent focal ischemia.
      NBQX 40, 60 or 100 mg/kg i.v., substantially reduced infarct size.
      Neuroprotection was maintained when the initiation of drug administration was
      withheld for 15, 45 or 90 min after permanent middle cerebral artery occlusion.
      Furthermore, NBQX did not induce heat shock protein in cingulate cortex, as do
      some N-methyl-D-aspartate antagonists. Thus, the compound is a potent
      neuroprotectant in focal ischemia and has an unusually long time window of
      effectiveness.

PMID- 8558418
TI  - Binding of bupivacaine to human serum proteins, isolated albumin and isolated
      alpha-1-acid glycoprotein. Differences between the two enantiomers are partly due
      to cooperativity.
AB  - Binding parameters of R(+)- and S(-)-bupivacaine were determined for human serum
      proteins, human alpha-1-acid glycoprotein (AAG) and human serum albumin (HSA),
      using ultrafiltration. Binding parameters were estimated according to the
      Scatchard model of the law of mass action using nonlinear regression. A sigmoid
      (cooperativity) term was added when needed. Both enantiomers exhibited a two site
      binding profile for human serum and for a solution containing AAG and HSA at
      physiological concentrations. At concentrations lower than 40 microM
      (concentrations encountered in clinical situations), the low capacity, high
      affinity apparent site was predominant and S(-)-bupivacaine exhibited a higher
      free fraction than R(+)-bupivacaine. At concentrations higher than 60 microM, the
      opposite situation was observed and the S(-) enantiomer showed much higher
      binding to AAG than the R(+) enantiomer. Two cooperativity phenomena occurred.
      Negative cooperativity was observed when AAG and HSA were combined in the same
      solution. S(-) and R(+) enantiomers exhibited different behavior toward purified
      AAG and HSA due in part to complex allosteric cooperativity (positive or negative
      depending on the ligand/protein ratio). In conclusion, we observed
      stereoselective binding of bupivacaine to AAG and HSA. Moreover, cooperativity
      occurred, and the behavior of the two enantiomers showed marked differences in
      this respect.

PMID- 8558419
TI  - The role of 5-HT3 receptors in periaqueductal gray-induced inhibition of
      nociceptive dorsal horn neurons in rats.
AB  - Electrical stimulation in the periaqueductal gray (PAG) can inhibit dorsal horn
      cell responses to both innocuous and noxious cutaneous stimuli. This inhibition
      is believed to be due to the release of serotonin (5-HT) into the dorsal horn of
      the spinal cord from descending axons of the nucleus raphe magnus and the
      adjacent reticular formation. It is still not clearly known which subtypes of 5
      HT receptors are involved in the PAG-induced inhibition. Extracellular single
      unit recordings of dorsal horn cell activity, in combination with drug
      administration through a microdialysis fiber, were used to test the role of 5-HT3
      receptors in PAG-induced inhibition. The responses of the cells to mechanical
      stimulation of the skin (BRUSH, PRESS and PINCH) and to the same stimuli while
      stimulating PAG were recorded. When the 5-HT3 antagonist, ondansetron, was
      perfused through the microdialysis fiber, not only was the background activity of
      the cell increased, but also the responses to BRUSH, PRESS and PINCH stimuli. The
      PAG-induced inhibition of responses to the same stimuli was partially or
      completely blocked by ondansetron. Another 5-HT3 antagonist, zacopride, did not
      increase the background activity or responses to PRESS and PINCH, yet this agent,
      like ondansetron, blocked PAG inhibition. The 5-HT3 agonist, phenylbiguanide,
      inhibited the background activity and the responses to mechanical stimuli. These
      results suggest that 5-HT released in the dorsal horn by stimulation in the PAG
      excites inhibitory interneurons through 5-HT3 receptors, resulting in inhibition
      of dorsal horn neurons.

PMID- 8558420
TI  - Interaction of nonpeptide angiotensin II receptor antagonists with the urate
      transporter in rat renal brush-border membranes.
AB  - The angiotensin II (AII) antagonist, losartan, increases uric acid excretion when
      administered to humans. However, the active metabolite of losartan, EXP 3174, and
      other nonpeptide AII antagonists such as eprosartan and SB 203220 are devoid of
      uricosuric activity. To investigate the mechanism of losartan-induced uricosuria,
      we examined the effects of losartan, EXP 3174, eprosartan and SB 203220 on OH- 
      dependent [14C]urate uptake into rat proximal tubule brush-border membrane
      vesicles. Losartan (10 microM) inhibited [14C]urate uptake at all time points
      examined, except at equilibrium (2 hr). Losartan had no effect on urate uptake in
      the absence of an OH- gradient. The inhibitory effect of losartan on urate uptake
      was concentration dependent (IC50 = 9.5 +/- 1.4 microM) and competitive in
      nature. The other AII antagonists also inhibited urate uptake but were 6-8-fold
      less potent than losartan with IC50 values of EXP 3174 (65 +/- 13 microM),
      eprosartan (60 +/- 7.0 microM) and SB 203220 (74 +/- 12.5 microM). In contrast to
      the effects of the nonpeptide AII antagonists, the peptide antagonist, Sar1,Ile8
      AII, as well as AII itself had no effect on urate uptake. These results suggest
      that the uricosuric activity of losartan is, at least in part, due to inhibition
      of urate reabsorption in the proximal tubule and is unrelated to AII receptor
      activity. Furthermore, losartan has a greater affinity for the urate/anion
      exchanger than the other AII antagonists tested. These results are in direct
      agreement with observations made after administration of these compounds to
      humans.

PMID- 8558417
TI  - Human cytochrome P450 isoform specificity in the regioselective metabolism of
      toluene and o-, m- and p-xylene.
AB  - The conversion of toluene and o-, m- and p-xylene to their respective side-chain
      and ring monohydroxylated metabolites by human liver microsomes was investigated.
      Methyl hydroxylation, to form a benzylalcohol, was the major metabolic pathway
      for all four methylbenzenes. With the exception of 2,4-dimethylphenol formation
      from m-xylene, ring hydroxylation accounted for < 5% of total metabolite
      formation. However, regioselectivity of ring hydroxylation was apparent, with
      hydroxylation occurring only at positions ortho and/or para to a methyl
      substituent. Toluene and each xylene isomer exhibited biphasic
      methylhydroxylation kinetics in human liver microsomes. The high-affinity
      component of each methylhydroxylation was selectively inhibited by
      diethyldithiocarbamate and correlated significantly with cytochrome P-4502E1
      (CYP2E1) content and activities in a panel of human liver microsomes. cDNA
      expressed CYP2E1 was shown to catalyze the formation of each benzylalcohol, with
      apparent Km values similar to those of the high affinity microsomal reactions. In
      contrast, the conversion of m-xylene to 2,4-dimethylphenol followed single enzyme
      Michaelis-Menten kinetics, was inhibited selectively by furafylline, and
      correlated significantly with known CYP1A2 catalyzed reactions. cDNA-expressed
      CYP1A2 converted m-xylene to 2,4-dimethylphenol, with an apparent Km similar to
      that of the microsomal reaction. Although CYP1A2 appears to be responsible for
      the formation of the minor (phenolic) metabolites of toluene and the xylene
      isomers, CYP2E1 catalyzed methylhydroxylation will be the major determinant of
      the clearance of these compounds in humans.

PMID- 8558421
TI  - Tachyphylaxis to angiotensin II and [Phe4]-angiotensin II in the rat mesentery in
      vivo.
AB  - The existence of tachyphylaxis to angiotensin II (Ang II) in vivo is not
      unequivocally established, and the hydroxyl group of the Tyr4 residue of Ang II
      has been suggested as a determinant of tachyphylaxis. In view of these
      observations, we conducted a series of experiments to assess and compare the
      ability of Ang II and [Phe4]-Ang II to induce tachyphylaxis in vivo. All
      experiments were performed in the autoperfused rat mesenteric vascular bed. The
      tachyphylaxis to intramesenteric (IMA) infusions of Ang II was minimal, and after
      120 min of continuous infusion (33 pmol/min), Ang II retained most of its
      vasoconstrictor activity (67.7 +/- 6.6% of the initial response). Also most of
      the agonist activity was retained even when Ang II was administered continuously
      in a dose-increasing manner (1-33 pmol/min). Continuous IMA infusions of single
      doses of [Phe4]-Ang II caused an initial full response that rapidly declined, and
      after 120 min retained only 18.2 +/- 9.2% of the initial response. Single
      continuous IMA infusion of [Phe4]-Ang II induced greater vasoconstrictor
      responses compared with vascular responses to the same doses delivered after the
      infusion of smaller doses. This difference was significant (P < .001, unpaired
      Student's t test) for all doses (10, 100, 330 and 1000 pmol/min) of [Phe4]-Ang
      II. In conclusion, although the development of tachyphylaxis to Ang II in vivo is
      minimal, tachyphylaxis to [Phe4]-Ang II does occur (at least in rat mesenteric
      vascular bed). Thus, omission of the hydroxyl group in position 4 dramatically
      increases the tachyphylactic potential, while preserving full agonist activity.
      These results suggest that the hydroxyl group of Tyr4 may protect the Ang II
      receptor from changes that induce tachyphylaxis.

PMID- 8558422
TI  - Beta adrenergic receptor activation attenuates the generation of inositol
      phosphates in the pregnant rat myometrium. Correlation with inhibition of Ca++
      influx, a cAMP-independent mechanism.
AB  - In the pregnant rat myometrium, an averaged 30% of inositol phosphate
      accumulation induced by carbachol and oxytocin was inhibited by oxodipine
      indicating that a part of receptor-mediated generation of inositol phosphates
      depended on Ca++ influx through voltage-gated Ca++ channels. In fura-2-loaded
      cells, carbachol and oxytocin caused a two-phase [Ca++]i response, made up of a
      transient [Ca++]i peak of about 700 nM followed by a sustained phase of about 120
      nM. Oxodipine reduced the [Ca++]i peak by 40% and the plateau phase by 50%,
      pointing to a contribution of Ca++ influx in both the [Ca++]i peak and sustained
      phase. Isoproterenol reduced inositol phosphate response to carbachol and
      oxytocin to an amount equivalent to that elicited by oxodipine. No additional
      reduction could be obtained in a combination of isoproterenol and oxodipine.
      Isoproterenol decreased by 40% the [Ca++]i peak and by 70% the [Ca++]i plateau
      phase. Differently from isoproterenol, forskolin did not affect inositol
      phosphate accumulation induced by oxytocin and failed to attenuate the [Ca++]i
      peak. The inhibitory effect of isoproterenol on both inositol phosphate
      accumulation and [Ca++]i increase induced by oxytocin was abolished by pertussis
      toxin. These data suggest that beta adrenergic receptor activation is linked via
      a cAMP-independent, pertussis toxin-sensitive process to an activation of K+
      channels, as revealed by use of selective K+ channel antagonists, with the
      consequent closure of voltage-gated Ca++ channels, resulting in the inhibition of
      the Ca(++)-associated generation of inositol phosphates.

PMID- 8558423
TI  - Tetrahydro-9-aminoacridine has mixed actions on muscarinic currents and blocks
      opioid currents in rat locus ceruleus neurons.
AB  - Actions of tetrahydro-9-aminoacridine (THA) on membrane properties of locus
      ceruleus neurons were examined using intracellular recording in superfused brain
      slices. Low concentrations of THA (300 nM-3 microM) caused a small inward current
      and a 10-fold increase in the potency of ACh to produce inward (excitatory)
      currents. No effect was seen on currents activated by carbachol, a muscarinic
      agonist not degraded by cholinesterases. High concentrations of THA (30-300
      microM) caused larger inward currents and a decrease in cell conductance. At
      these concentrations THA inhibited inward currents induced by carbachol (IC50 =
      33 microM) and by substance P, which reportedly excites locus ceruleus neurons
      via the same ionic mechanism as muscarinic agonists. Furthermore, outward
      currents activated by opioids could be completely blocked (IC50 = 15 microM).
      Also affected was the action potential waveform, which was slower to rise, longer
      in duration and smaller in amplitude. The results suggest that THA has
      predominantly excitatory effects on locus ceruleus neurons--both by greatly
      enhancing the actions of ACh and by producing a small inward current. At high
      concentrations effects are mixed and include inhibition of muscarinic currents,
      as well as of resting and agonist-induced inwardly rectifying potassium currents.
      The block of opioid currents by THA was not consistent with inhibition of a
      cationic conductance as recently proposed.

PMID- 8558424
TI  - Carbamazepine inhibition of N-methyl-D-aspartate-evoked calcium influx in rat
      cerebellar granule cells.
AB  - The effect of carbamazepine (CBZ) on N-methyl-D-aspartate (NMDA)-stimulated CA++
      influx in rat cerebellar granule cells was studied by use of fura-2
      microfluorometry. CBZ inhibited the rise in intracellular free Ca++ concentration
      ([Ca++]i) induced by NMDA and glycine in a rapid reversible and concentration
      dependent manner. CBZ's inhibition of the [Ca++]i increase was noncompetitive
      with respect to NMDA, glycine and the facilitatory neurosteroid pregnenolone
      sulfate. The degree of inhibition of the NMDA response produced by CBZ increased
      with increasing concentrations of extracellular KCl. Excluding non-NMDA receptor
      mediated contributions to Ca++ influx, depolarization by 50 mM KCl resulted in a
      20-fold decrease (from 723 to 33 microM) in the IC50 for CBZ blockade of the NMDA
      response. Thus, significant blockade of NMDA receptor responses in cerebellar
      granule cells can occur at concentrations of CBZ within the therapeutic range
      under conditions believed to accompany seizures. Moreover, the common toxic side
      effects of CBZ, which include signs of cerebellar dysfunction, may occur as a
      result of CBZ blockade of the NMDA receptors of cerebellar granule cells.

PMID- 8558425
TI  - ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1
      receptor agonist: in vitro characterization and effects in animal models of
      Parkinson's disease.
AB  - (-)-Trans 9,10-hydroxy-2-propyl-4,5,5a,6,7,11b-hexahydro-3-thia-5- azacyclopent-1
      ena[c]phenanthrene hydrochloride (A-86929) is a potent and selective full agonist
      at the dopamine (DA) D1-like receptor. Judging by its binding affinities to the
      D1 and D2 classes of receptors, the compound is approximately 20-fold D1 receptor
      selective, whereas relative potencies based on functional in vitro assays
      indicate that A-86929 is greater than 400-fold D1-selective. A-86929 has moderate
      to weak (Ki > 1 microM) affinity at other monoaminergic and peptidergic
      receptors, at ion channels and at monoamine uptake sites. The catechol of A-86929
      was bis-acetylated to produce the prodrug, (-)-trans 9,10-acetoxy-2-propyl
      4,5,5a,6,7,11-b-hexahydro-3-thia- 5-azacyclopent-1-ena[c]phenanthrene
      hydrochloride (ABT-431), which is more chemically stable yet is rapidly converted
      to the parent compound with a half-life of less than 1 min in plasma. Both A
      86929 and ABT-431 produced contralateral rotation in rats bearing unilateral 6
      hydroxydopamine lesions, with ED50 values of 0.24 mumol/kg s.c. and 0.54 mumol/kg
      s.c., respectively. A-86929 and ABT-431 improved behavioral disability scores and
      increased locomotor activity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      lesioned marmoset model of Parkinson's disease in a dose-dependent manner (the
      minimum effective dose was 0.10 mumol/kg s.c.). When administered three times
      daily for 30 consecutive days to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      lesioned marmosets, A-86929 significantly improved disability scores throughout
      the duration of the study. Current Parkinson's disease therapy includes L-dopa,
      which stimulates both classes of DA receptors by virtue of its conversion to DA
      in vivo, and direct-acting D2-selective agonists. Stimulation of the D2 receptor,
      which is associated with all current DA agonist-based therapies, may contribute
      to their dose-limiting side effects. An agent such as A-86929 (or its prodrug ABT
      431), which selectively stimulates the D1 receptor, may represent a novel
      mechanism for Parkinson's disease therapy with the potential for an improved side
      effect profile and, consequently, improved patient compliance.

PMID- 8558426
TI  - Block of the N-methyl-D-aspartate receptor by remacemide and its des-glycine
      metabolite.
AB  - The anticonvulsant and neuroprotective properties of remacemide [(+/-)-2-amino-N
      (1-methyl-1,2-diphenylethyl)acetamide] and its active des-glycine metabolite [(+/
      )-1-methyl-1,2-diphenylethylamine] may result in part from blockade of N-methyl-D
      aspartate (NMDA) receptors. The blocking actions of the remacemide enantiomers
      and their des-glycinates were investigated in whole cell voltage-clamp recordings
      from cultured rat hippocampal neurons and in binding studies with [3H]dizocilpine
      in rat forebrain membranes. (+/-)-Remacemide caused a rapid and reversible
      inhibition of NMDA-evoked current; the R(+)- and S(-)-enantiomers were roughly
      equipotent (IC50 values at -60 mV, 67 and 75 microM, respectively). In contrast,
      the block by the S(+)- and R(-)-des-glycine analogs was slower, more potent and
      occurred in a stereoselective fashion (IC50 values, 0.7 and 4 microM). The block
      by S(+)-des-glycine remacemide was strongly use- and voltage-dependent, and, in
      addition, could be occluded by Mg++, indicating that it occurs by an open channel
      mechanism. In contrast, the block by R(+)-remacemide was only partially voltage
      dependent, suggesting that it occurs by both channel blocking and nonchannel
      blocking (allosteric) mechanisms. Support for an allosteric mechanism was
      obtained in nonequilibrium [3H]dizocilpine binding studies where it was observed
      that 100 microM R(+)-remacemide slowed the dissociation of the radioligand
      [whereas 10 microM S(+)-des-glycine remacemide did not]. Neither R(+)-remacemide
      nor S(+)-des-glycine remacemide inhibited currents evoked by kainate, alpha-amino
      3-hydroxy-5-methyl-4-isoxazoleproprionate or gamma-aminobutyric acid. We conclude
      that des-glycine remacemide is a potent and selective channel blocking NMDA
      receptor antagonist, whereas remacemide is weaker and inhibits NMDA receptors by
      both channel blocking and nonchannel blocking actions.

PMID- 8558427
TI  - Evidence that a nereistoxin metabolite, and not nereistoxin itself, reduces
      neuronal nicotinic receptors: studies in the whole chick ciliary ganglion, on
      isolated neurons and immunoprecipitated receptors.
AB  - Nereistoxin (100 microM, 2-10 min) blocks nicotinic receptors in the intact chick
      ciliary ganglion. This effect mimics blockade by the reducing agent
      dithiothreitol (2 mM, 20 min), which is not reversed until oxidation with
      dithiobisnitrobenzoic acid (1 mM, 5 min). After treating intact ganglia with
      either nereistoxin or dithiothreitol, the affinity alkylating agent
      bromoacetylcholine causes irreversible blockade that cannot be reversed by
      dithiobisnitrobenzoic acid. These data suggest that nereistoxin, or a metabolite,
      acts to reduce nicotinic receptors, although nereistoxin differs from
      dithiothreitol in that agonists only partially protect against nereistoxin
      reduction. In studies on chick retina, we previously proposed that a metabolite
      of nereistoxin (such as dihydronereistoxin) is the actual reducing agent for
      neuronal nicotinic receptors. Current findings in chick ciliary ganglion
      supporting this hypothesis include: 1) changing pH alters the minimal nereistoxin
      concentration needed for blockade in intact ganglia, but has little effect on the
      minimal concentration needed for dithiothreitol, 2) application of a quaternary
      analog of nereistoxin has little effect on intact ganglion, but a quaternary
      analog of dihydronereistoxin blocks nicotinic receptors by reduction, 3)
      nereistoxin weakly oxidizes rather than reduces immunoprecipitated receptors from
      chick brain and 4) in whole-cell patch-clamp studies, nereistoxin clearly does
      not reduce receptors on chick ciliary neurons, although dihydronereistoxin mimics
      receptor blockade by dithiothreitol, and requires oxidation by
      dithiobisnitrobenzoic acid for reactivation. Together, these data suggest that
      nereistoxin is not a direct reducing agent for neuronal nicotinic receptors.

PMID- 8558428
TI  - Acetylcholine-induced chloride current oscillations in swine tracheal smooth
      muscle cells.
AB  - The activation of muscarinic receptors by acetylcholine (ACh) in tracheal smooth
      muscle cells induced Ca++ oscillations, measured as the activation of Ca(++)
      dependent Cl- currents (Clca) at the K+ equilibrium potential. The currents were
      not abolished by replacement of external and internal K+ with Cs+ but decreased
      after reduction in internal Cl- concentration or extracellular application of
      niflumic acid, a Cl- channel blocker. The Clca oscillations were dependent on
      external Ca++ concentration ([Ca++]e). The mean current and frequency increased
      with increasing [Ca++]e, were enhanced by Bay K 8644 and were inhibited by
      verapamil, suggesting a role for voltage-operated Ca++ channels (VOC). Steady
      state increases in Clca induced by 10(-6) M ACh could be converted to
      oscillations by reducing [Ca++]e or by buffering intracellular Ca++ with
      ethyleneglycolbis-N,N,N'-N'-tetraacetic acid (EGTA). Oscillations in Clca induced
      by 3 x 10(-8) and 10(-7) M ACh were more sensitive to EGTA than those induced by
      10(-6) M ACh. Caffeine induced nonoscillatory, transient increases in Clca and
      reduced subsequent ACh-induced increases in Clca. The oscillatory patterns of
      Clca induced by ACh and the effects of modification of Ca++ influx were similar
      for oscillations in intracellular Ca++ concentration [Ca++]i as measured with
      confocal microfluorimetry. Thus, ACh-induced Clca oscillations reflect
      fluctuations in [Ca++]i that are consistent with initiation of Ca++ release from
      inositol-1,4,5-trisphosphate-(IP3)sensitive Ca++ stores. Maintenance of the
      oscillations requires Ca++ influx, in part through voltage-operated Ca++
      channels.

PMID- 8558429
TI  - Effects of the specific angiotensin II receptor antagonist losartan on urate
      homeostasis and intestinal urate transport.
AB  - Possible mechanisms for the hypouricemic effects of the angiotensin II receptor
      antagonist losartan were examined using rats with experimental chronic renal
      failure (CRF) and control animals. The results show that losartan has a
      uricosuric effect in rats with normal or decreased renal function. Renal
      clearance of urate was increased 3-fold in CRF rats and 2-fold in control rats
      after 7 days of intraperitoneal losartan administration. Although the results
      show that losartan and its metabolite EXP-3174 alter urate and Cl- transport
      across isolated short-circuited intestine, these agents do not promote urate
      secretion into the intestinal lumen. Unidirectional urate and Cl- fluxes were
      reduced across normal rat colon and unaltered in the small intestine in the
      presence of losartan. In CRF rat colon, net secretion of urate and Cl- was
      abolished after losartan addition at 10(-5) M. Transport across the small
      intestine of CRF rats did not change in the presence of a similar concentration
      of drug. Losartan treatment of CRF rats before the removal of colonic tissues
      reversed the basal net secretion of urate to net absorption. These results
      suggest that the changes in intestinal transport observed in the presence of
      losartan appear to be mediated via the angiotensin II receptor antagonistic
      action of this drug. Direct determination of the effects of angiotensin II on
      urate and Cl- transport across colonic tissues from control animals revealed a
      significant angiotensin II stimulation of urate secretion. These angiotensin II
      induced alterations in transport were inhibitable by losartan.

PMID- 8558430
TI  - ATP depletion by iodoacetate and cyanide in renal distal tubular cells.
AB  - Suspensions of proximal tubular and distal tubular (DT) cells from rat kidney
      were treated with iodoacetate and potassium cyanide (IAA+KCN) as a model to
      assess injury from ATP depletion. Cells were also incubated under N2/CO2 to
      assess if they respond similarly to ATP depletion due to hypoxia. Based on
      cytotoxic effects of IAA (lactate dehydrogenase [LDH] release, protein sulfhydryl
      depletion) and inhibition of lactate formation, 20 microM IAA was chosen with 1
      mM KCN to inhibit cellular ATP generation. DT cells exhibited significantly
      greater LDH release due to both IAA + KCN and hypoxia than PT cells. Mechanisms
      of cellular injury and the ability of various strategies to protect against
      (IAA+KCN)-induced injury were then studied in isolated renal DT cells to
      investigate factors responsible for the enhanced susceptibility of this renal
      cell population, about which little metabolic and toxicological information is
      known. IAA+KCN produced marked depletion of ATP, only minimal changes in cellular
      content of glutathione, but significantly decreased cellular content of
      glutathione disulfide, suggesting generation of a proreductant environment.
      Extracellular acidosis (pH 6.2 vs. 7.4) completely prevented the increase in LDH
      release during 2-hr incubations with IAA+KCN and partially prevented ATP
      depletion. Similarly, preincubation with glutathione, glycine, ATP, or adenosine
      significantly protected DT cells from injury. Complete restoration of cellular
      ATP content was not required for protection, although viability correlated better
      with cellular content of total adenine nucleotides. These studies are the first
      to explore cellular energetics and cytotoxicity in renal DT cells and demonstrate
      that these cells are highly sensitive to injury from ATP depletion due to either
      IAA+KCN or hypoxia.

PMID- 8558431
TI  - Pharmacokinetics and blood-brain barrier transport of [3H]-biotinylated
      phosphorothioate oligodeoxynucleotide conjugated to a vector-mediated drug
      delivery system.
AB  - Antisense phosphorothioate oligodeoxynucleotides (PS-ODNs) are potential
      neuropharmaceuticals should these agents be made transportable through the blood
      brain barrier (BBB) in vivo. The present studies report on attempts to enhance
      brain uptake of systemically administered 3'-biotinylated PS-ODN (bio-PS-ODN) by
      conjugation to a complex of streptavidin (SA) and the OX26 monoclonal antibody to
      the rat transferrin receptor. This antibody undergoes receptor-mediated
      transcytosis through the BBB and the OX26/SA conjugate mediates BBB transport of
      biotinylated therapeutics. The brain uptake of unconjugated [3H]-bio-PS-ODN
      approximated that of [14C]sucrose, a plasma volume marker that is not
      significantly transported through the BBB. Conjugation of [3H]-bio-PS-ODN to the
      OX26/SA vector resulted in a marked increase in BBB transport and the
      permeability-surface area (PS) product of the conjugate was 4.0
      microliters/min/g. However, when the bio-PS-ODN/OX26-SA conjugate was injected
      intravenously in anesthetized rats, the BBB PS product of the conjugate was
      reduced 23-fold to a value of 0.173 +/- 0.006 microliters/min/g. The marked
      inhibition of vector-mediated transport of the bio-PS-ODN after intravenous
      injection was due to avid plasma protein binding of PS-ODNs, as has been
      demonstrated with protein binding assays and internal carotid artery perfusion
      studies. In conclusion, although PS-ODNs have the advantage of increased
      metabolic stability and resistance to endonucleases in vivo, the BBB transport of
      antisense PS-ODN therapeutics conjugated to the brain drug delivery vector
      OX26/SA is markedly attenuated due to plasma protein-binding effects.

PMID- 8558432
TI  - Metabolism of 3-methylindole by vaccinia-expressed P450 enzymes: correlation of 3
      methyleneindolenine formation and protein-binding.
AB  - The toxicity of 3-methylindole (3 MI), a selective pneumotoxin, is dependent upon
      cytochrome P450-mediated bioactivation 3. Using vaccinia-expressed P450 enzymes,
      the metabolites of radiolabeled 3 MI produced by 14 individual P450s were
      identified and quantified by high performance liquid chromatography. Indole-3
      carbinol was produced from incubations of 3 MI with only four enzymes. Although 3
      methyloxindole was a product of several P450s, human 1A2 was most efficient in
      producing this metabolite. The toxic intermediate of 3 MI is believed to be a
      reactive methylene imine, 3-methyleneindolenine. In this study, this intermediate
      was detected as its mercapturate adduct, when N-acetylcysteine was added to the
      incubations. 3-Methyleneindolenine was produced by CYP2A6 at a rate of 50.9 +/-
      8.9 pmol/mg protein/hr and by CYP2F1 at a rate of 205.7 +/- 12.5 pmol/mg/hr. The
      mouse 1a-2 and rabbit 4B1 enzymes produced the reactive intermediate in amounts
      that exceeded that of the human 2F1 enzyme by 1.4-fold and 1.9-fold,
      respectively. The toxicity of 3 MI is believed to be due to covalent binding of a
      P450-generated intermediate to critical pulmonary proteins. Comparison of
      covalent binding studies to the formation of the metabolites revealed a strong
      correlation between the amount of the 3 MI adduct detected and covalent binding.
      This study showed that the methylene imine electrophile is produced by only a few
      P450 enzymes and is the metabolite responsible for the covalent binding and
      presumably, the toxicity of 3 MI. Remarkable product preferences between the
      desaturation pathway to form the methyleneindolenine by CYP2F1 and the ring
      epoxidation pathway to form the oxindole by CYP1A2, were observed.

PMID- 8558433
TI  - Electrocorticographic desynchronization after application of visceral and somatic
      noxious stimuli in urethane-anesthetized rats: effect of intrathecal
      administration of tachykinin (NK 1 or NK 2) receptor antagonists.
AB  - We investigated the electrocortical (E.Co.G) correlates of visceral (topical
      capsaicin application or overdistension of the urinary bladder) and somatic
      (perineal pinching) painful stimulation in urethane-anesthetized rats and their
      modulation by intrathecal application of selective tachykinins receptors (NK 1
      and NK 2) antagonists. Vesical overdistension or topical capsaicin on the bladder
      serosal surface produced an immediate and lasting E.Co.G. desynchronization
      resembling a cortical arousal. A second application of capsaicin was ineffective.
      Bladder contraction induced by topical acetylcholine did not alter E.Co.G. A
      desynchronized E.Co.G. was also induced by pinching of the perineal area of the
      rat. Intrathecal administration of lidocaine at lumbosacral level abolished the
      E.Co.G. desynchronization induced by both visceral and somatic noxious
      stimulation. On the other hand capsaicin-induced or over-distension (but not
      pinching-induced) E.Co.G. desynchronization disappeared in animals systemically
      pretreated with capsaicin or after intrathecal administration of NK 1 tachykinin
      receptor antagonists such as the peptide GR 82334 or the nonpeptide RP 67580,
      whereas the inactive enantiomer RP 68651 or the nonpeptide NK 2 antagonists SR
      48968 were ineffective. In conclusion, the experimental model described herein,
      allowing a quantitative analysis of the E.Co.G. correlates of visceral and
      somatic noxious stimulation in urethane-anesthetized rats, provides evidence for
      a specific neural pathway carrying bladder-arising visceral (both mechanical and
      chemical) nociception that uses pelvic capsaicin-sensitive afferents projecting
      to NK 1 (but not NK 2) bearing spinal neurons and that ultimately leads to
      activation of cortical areas.

PMID- 8558434
TI  - Uptake of cimetidine into syncytial microvillus membrane vesicles of human term
      placenta.
AB  - Uptake of the H2-receptor antagonist, cimetidine, into syncytial microvillus
      membrane vesicles of human term placenta was investigated to clarify whether an
      active transport mechanism can be responsible for the observed barrier of the
      human placenta for cimetidine. Imposition of an outwardly directed H(+)-gradient
      stimulated cimetidine uptake, resulting in a small transient overshoot. The H(+)
      gradient-dependent peak uptake was decreased under voltage-clamped conditions by
      carbonyl cyanide p-trifluoromethoxy-phenylhydrazone, suggesting the presence of
      an organic cation-proton exchange mechanism. Uptake was partially, but
      significantly, inhibited by organic cation transport inhibitors, H2-receptor
      antagonists and several other cationic drugs, providing further evidence for
      mediated uptake. H(+)-gradient-dependent cimetidine uptake was saturable and
      characterized by a low-affinity (Km) of 6.3 mM and Vmax of 17.5 nmol/mg
      protein/10 sec. We conclude that the system cannot play an important role in the
      barrier function of the human placenta in the transport of cimetidine. Rather
      than active transport, other factors, as for instance the degree of ionization of
      cimetidine at physiological pH, seem to be a more likely explanation for the low
      clearance of cimetidine across the human placenta.

PMID- 8558435
TI  - Autoradiographic evidence for the modulation of in vivo sigma receptor labeling
      by neuropeptide Y and calcitonin gene-related peptide in the mouse brain.
AB  - Peptides of the neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP)
      families have been reported to modulate, in vivo, sigma receptor systems in the
      mouse and rat hippocampal formation. In an attempt to determine if these
      interactions were specific to the hippocampal formation, quantitative ex vivo
      autoradiography was used with (+)(-)[3H]SKF 10,047 as sigma ligand after i.c.v.
      injections of various NPY and CGRP peptides. High levels of specific (+)(
      )[3H]SKF 10,047 labeling were concentrated in various cranial nerve nuclei,
      whereas lower but still significant amounts of labeling were seen in the cortex,
      hippocampus, various hypothalamic nuclei, red nucleus, substantia nigra, central
      gray and cerebellum. In all brain areas enriched with specific (+)(-)[3H]SKF
      10,047/sigma labeling, the Y1 receptor subtype agonist [Leu31Pro34]-NPY, as well
      as peptide YY and rCGRP beta, inhibited, to a rather similar extent, (+)(
      )[3H]SKF 10,047 labeling. The Y2 receptor agonist NPY13-36 had no effect in any
      of the regions studied. These results extend findings obtained in the hippocampal
      formation and demonstrate the existence of in vivo modulatory effects of NPY and
      CGRP-related peptides on sigma sites throughout the mouse brain.

PMID- 8558436
TI  - A catechol derivative (4-methylcatechol) accelerates the recovery from
      experimental acrylamide-induced neuropathy.
AB  - Acrylamide (ACR) monomer produces neuropathy of the dying-back type and 4
      methylcatechol (4-MC) is a potent stimulator of endogenous nerve growth factor
      synthesis. In the present study, we investigated the efficacy of 4-MC in
      promoting recovery from experimental ACR neuropathy in rats. Twenty-two Sprague
      Dawley rats were made neuropathic by ACR injections. They showed hindlimb
      paralysis, increment of landing foot spread distance and a statistically
      significant reduction in motor nerve conduction velocity. After the ACR
      neuropathy had been established, 12 of the rats were administered 4-MC for 2
      weeks, and the other 10 were injected with phosphate-buffered saline alone. 4-MC
      administered ACR neuropathy rats showed improvement, i.e., a decrease in landing
      foot spread distance, increase in motor nerve conduction velocity and increase in
      nerve growth factor content in the sciatic nerves in comparison with the
      corresponding values for ACR neuropathy rats given phosphate-buffered saline
      alone. A decreased number of large myelinated fiber with a reciprocal increase in
      small myelinated fiber number also was seen in the ACR neuropathy rats; however,
      this change was ameliorated in part by the administration of 4-MC. Therefore,
      these findings suggest that 4-MC can accelerate the recovery process clinically,
      electrophysiologically, biochemically and neuropathologically.

PMID- 8558437
TI  - Forskolin-mediated induction of CYP3A1 mRNA expression in primary rat hepatocytes
      is independent of elevated intracellular cyclic AMP.
AB  - Previously, we demonstrated that elevated levels of cyclic AMP (cAMP) repressed
      phenobarbital (PB)-inducible cytochrome P450 (CYP)2B gene expression in primary
      rat hepatocyte cultures. Although CYP3A1 induction by PB was similarly repressed
      by most of the cAMP-enhancing strategies, forskolin additions in particular
      resulted in marked stimulation of CYP3A1 expression. Here we examined whether
      this effect was due to forskolin's ability to activate adenylate cyclase. By
      using a specific ELISA for assessment of intracellular cAMP levels, we determined
      that forskolin and a water-soluble analog (L858051; 7 beta-desacetyl-7 beta-(N
      methylpiperazine)) were equipotent in stimulating adenylate cyclase activity.
      However, only forskolin and its inactive 1,9-dideoxy analog were active as
      inducers of CYP3A1. In comparative studies, both dexamethasone and PB were
      ineffective in stimulating production of intracellular cAMP. Furthermore,
      treatment of hepatocytes with glucagon, dibutyryl-cAMP, or N6O2'-dibutyryl-cyclic
      GMP, resulted in no detectable enhancement of CYP3A1 gene expression. These
      results demonstrated that CYP3A1 induction by forskolin is independent of cAMP,
      and instead is likely to involve a direct chemical effect of forskolin on the
      CYP3A1 activation pathway.

PMID- 8558438
TI  - Cationized hyperimmune immunoglobulins: pharmacokinetics, toxicity evaluation and
      treatment of human immunodeficiency virus-infected human-peripheral blood
      lymphocytes-severe combined immune deficiency mice.
AB  - The in vivo pharmacokinetics and efficacy of cationized human immunoglobulins in
      the human-peripheral blood lymphocytes-severe combined immune deficiency mouse
      model were evaluated in the present studies using the severe combined
      immunodeficient mouse transplanted with human lymphocytes and infected with human
      immunodeficiency virus (HIV)-1. Immunoglobulins from noninfected humans and from
      HIV-infected individuals were cationized. The pharmacokinetic analysis showed
      that the cationized immunoglobulins have a markedly reduced mean residence time
      and a marked increase in organ uptake compared to the native immunoglobulins. The
      toxicity studies performed with homologous immunoglobulins in BALB/c mice
      demonstrated cationized homologous immunoglobulins have no tissue toxicity at a
      daily dose of 7.5 mg/kg. Treatment of HIV-infected severe combined immune
      deficiency mice that were transplanted with human lymphocytes demonstrated
      therapeutic efficacy for a 2-week treatment at a dose of 5 mg/kg cationized HIV
      immune globulin. In conclusion, cationized immunoglobulins are potential antibody
      based therapeutics for the treatment of acquired immune deficiency syndrome;
      cationized antibodies undergo enhanced transport into lymphocytes and when
      homologous cationized immunoglobulins are administered there is no measurable
      tissue toxicity.

PMID- 8558439
TI  - Variable effects of L-arginine analogs on L-arginine-nitric oxide pathway in
      human neutrophils and platelets may relate to different nitric oxide synthase
      isoforms.
AB  - L-Arginine analogs are generally used as inhibitors of nitric oxide (NO)
      synthesis in a variety of tissues. We studied the effects of two analogs of L
      arginine on L-arginine transport and NO synthase activity in human
      polymorphonuclear leukocytes (PMN) and platelets. Both NG-nitro-L-arginine
      methylester and N omega-nitro-L-arginine reduced the uptake of 3H-L-arginine in
      human PMN and platelets in a concentration-dependent fashion. The inhibitory
      effect of these analogs on the uptake of 3H-L-arginine was greater in PMN than in
      platelets (P < .05). Both agents also modestly inhibited NO synthase activity in
      platelet cytosol, whereas neither had significant and specific effect on NO
      synthase activity in the PMN cytosol. NO synthase activity in intact PMN, but not
      in platelets, was insensitive to exogenous Ca++. Reverse transcription-polymerase
      chain reaction products showed the presence of endothelial constitutive (756 bp)
      and the neuronal constitutive (629 bp) NO synthase isoforms in human platelets
      and PMN, respectively. This was further confirmed by Southern analysis. Thus the
      classic inhibitors of NO synthesis primarily decrease L-arginine uptake in PMN
      and platelets, and significantly affect NO synthase activity only in platelets.
      These differences may, at least in part, be due to the presence of different NO
      synthase isoform in platelets and PMN.

PMID- 8558440
TI  - Suppression of rat hepatic microsomal cytochromes P450 by cyclophosphamide is
      correlated with plasma thyroid hormone levels and displays differential strain
      sensitivity.
AB  - Strain differences in cytochrome P450 (P450) expression were investigated in
      Sprague-Dawley (SDs) compared with Fischer 344s (F344s) rats after administration
      of cyclophosphamide (CPA). Animals received a single dose of CPA with sacrifice
      occurring 6 days post-treatment. At 130 mg/kg, male F344s displayed a greater
      sensitivity to CPA, as evidenced by a 68% loss of total hepatic microsomal P450
      compared with only 35% in SDs. The most dramatic change in P450 was the loss of
      2C11 (84% in F344s, 52% in SDs). In the SD, individual rat 2C11 activity was
      correlated (r2 = 0.76), with the level of plasma thyroxine in that animal. In
      male F344s administered CPA at 50 mg/kg, 43 and 44% losses in 2C11 activity (P <
      .05) and thyroxine (P < .01), respectively, were observed, whereas activities
      characteristic of P450s 2C11, 3A2, 2A2, 2C6 and 2E1/1A2 were unaffected in SDs at
      this dose. CPA also produced suppression of P450 in female SDs, including female
      specific 2C12. Correlation was observed between the loss of P450 expression and
      change in body weight after treatment in both male and female animals, suggesting
      that CPA downregulates P450 expression secondary to decreased caloric intake. The
      anorectic effect of CPA is believed to result from potent central nervous system
      stimulation, accompanied by a state of adaptive hypothyroidism. It has been
      reported that CPA produces "feminization" of P450 expression in male rats.
      However, our findings suggest the alternative explanation that the effects of CPA
      on P450 expression result from decreased caloric intake.

PMID- 8558442
TI  - Long-term safety of the aminobisphosphonate alendronate in adult dogs. I. General
      safety and biomechanical properties of bone.
AB  - Alendronate (4-amino-1-hydroxybutylidene bisphosphonate, ALN) is an
      aminobisphosphonate that is being developed for the treatment of diseases
      characterized by increased bone resorption. The purpose of this study was to
      assess the long-term safety of ALN with special emphasis on bone strength and
      bone morphology. Thirty-two (16 males and 16 females) 83- to 86-week-old beagle
      dogs were treated p.o. for up to 3 years with ALN at 0.00, 0.25, 0.5 or 1.0
      mg/kg/day. The following parameters of toxicity were assessed: physical signs,
      body weight, ophthalmology, radiographic evaluation of bone, electrocardiography,
      hematology, clinical chemistry, urinalysis, necropsy including organ weight
      assessment, histopathology and biomechanical testing of bone. There were no
      apparent compound-related alterations in any of the above mentioned parameters
      except the expected changes (related to the pharmacological activity of ALN) in
      serum phosphorus and Ca concentrations and in the histology of bones with active
      endochondral bone formation (rib). There were mild transient reductions in the
      serum phosphorus and Ca concentrations at the 1.0 mg/kg/day dose level during the
      early part of the study. There was a dose-dependent delay in bone remodeling in
      the ribs of all dogs treated with ALN. There was no similar change in the tibia.
      Most importantly, there were no spontaneous fractures and there were no changes
      in the structural properties of femoral or vertebral bone. The total ALN content
      of bone in an average dog (10 kg) after 3 years of treatment with approximately
      five items of the intended dose for the treatment of osteoporosis was
      approximately 8 mg, which is only 0.001% of total bone mass (700 g).
      Introduction.

PMID- 8558441
TI  - The 21-aminosteroid tirilazad mesylate can ameliorate inflammatory bowel disease
      in rats.
AB  - The 21-aminosteroid tirilazad mesylate (U74006F) is a lipophilic antioxidant and
      free radical scavenger that has been reported to attenuate brain or spinal cord
      injury caused by trauma, stroke, ischemia and reperfusion injury. In this study,
      we have examined the effect of U74006F in reducing the inflammatory parameters of
      trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in
      rats. To induce IBD, rats were given ethanolic TNBS intracolonically. Rats
      received either 1) TNBS and U74006F 2) TNBS and vehicle or 3) saline and vehicle.
      Rats were sacrificed 1, 2 and 3 weeks after IBD induction. Colon to body weight
      ratio (an index of tissue edema) was markedly increased in the vehicle-treated
      IBD rats after 1 week of administration of TNBS. The ratio was significantly
      lower after U74006F treatment and the trend remained even after 3 weeks of
      chronic inflammation. Myeloperoxidase (MPO) activity in vehicle-treated IBD rats
      was substantially increased compared with controls during the entire 3 weeks of
      the experiment. U74006F-treated animals had significantly reduced MPO activity
      (60% lower) when compared with vehicle-treated animals at the end of the second
      and third weeks. These observations were confirmed by histopathology studies
      showing reduced granulocyte infiltration after drug treatment. U74006F treatment
      decreased basal (by 70%) and fMLP stimulated (by 75%) superoxide generation from
      colonic tissue from IBD rats compared with vehicle treatment after 2 weeks, but
      there was no apparent difference in superoxide generation among all three groups
      after 3 weeks. The results of this study suggested that administration of U74006F
      effectively reduces the inflammatory parameters in this chronic rat model of IBD.
      As such, U74006F may be therapeutically beneficial for the treatment of IBD in
      humans.

PMID- 8558443
TI  - Long-term safety of the aminobisphosphonate alendronate in adult dogs. II.
      Histomorphometric analysis of the L5 vertebrae.
AB  - Osteoporosis is a major health problem. Bisphosphonates are synthetic compounds
      that are taken up preferentially by the skeleton and suppress osteoclast-mediated
      bone resorption. Alendronate (ALN) is an aminobisphosphonate used in the
      treatment of diseases characterized by increased bone resorption including
      osteoporosis. The purpose of this study was to rule out possible adverse effects
      of the chronic administration of ALN on the quality of bone. Thirty-one 20- to 21
      month-old beagles (n = 7-8 per group, females and males) were treated p.o. for
      157 weeks with ALN at 0.00, 0.25, 0.5 or 1.00 mg/kg/day and labeled in vivo with
      oxytetracycline and calcein. Undecalcified bone sections obtained from the fifth
      lumbar vertebra were evaluated by static and dynamic histomorphometry. Cortical
      or cancellous bone volume and indices of architecture were not affected by
      treatment. Osteoid thickness and mineralization lag time were not changed by
      treatment. Tissue level bone turnover was inhibited in a dose-dependent manner in
      males. The results indicate that long-term ALN administration at up to 5 times
      the dose used for treatment of osteoporosis in clinical trials causes no
      abnormalities in bone remodeling or bone structure.

PMID- 8558444
TI  - 125I-APE binding to adenosine receptors in coronary artery: photoaffinity
      labeling with 125I-azidoAPE.
AB  - Coronary arteries are known to contain adenosine receptors that elicit
      vasodilation. Past attempts to characterize these receptors by radioligand
      binding have been unsuccessful. In the present study, a newly synthesized
      iodinated adenosine analogue, [125I]2-[2-(4-amino-3
      iodophenhyl)ethylamino]adenosine (125I-APE), was found to bind to adenosine
      receptors in porcine coronary artery smooth muscle membranes. Specific 125I-APE
      binding is temperature sensitive with maximal binding detected at 4 degrees C.
      125I-APE binds to a high affinity low density site with a KD of 0.59 +/- 0.11 nM
      and a Bmax 7 +/- 0.8 fmoles/mg protein. A high abundance lower affinity site is
      suggested by the fact that APE competes for 125I-APE binding with a concentration
      that inhibits 50% (IC50) of 0.96 microM. Competition with various other adenosine
      receptor agonists results in a potency order of (IC50, microM): 2
      phenylaminoadenosine (CV 1808, 0.34) > APE (0.96) > CGS 22988 (5.2) > 2
      chloroadenosine (30) > CGS 21680 and NECA (> 100). Agonist binding is not
      affected by GppNHp (10(-7)-10(-3) M). Among antagonists the potency order is
      (microM): CGS 15943 (1.1) > 8-(3-chlorostyryl)-caffeine (CSC, 5.3) > 8
      sulfophenyltheophylline (SPT, 86) > theophylline (> 100). These binding
      characteristics are similar to the properties of a putative A4 binding site
      characteristic of A2a receptors assayed at a low temperature. Photoaffinity
      labeling of porcine coronary artery membrane proteins with the azide derivative
      of 125I-APE revealed a 45,000-Da binding site. Photolabeling is prevented by
      coincubation of membranes at 4 degrees C with various adenosine receptor
      antagonists (1 microM CSC, 1 microM CGS 15943 or 100 microM theophylline). In
      conclusion, adenosine receptors of coronary arteries have been detected for the
      first time by radioligand binding and photoaffinity labeling. This ligand appears
      to label porcine A4 binding sites that may correspond to A2a receptors assayed at
      4 degrees C.

PMID- 8558445
TI  - Stable expression, pharmacologic properties and regulation of the human neuronal
      nicotinic acetylcholine alpha 4 beta 2 receptor.
AB  - (-)-Nicotine, the prototypical agonist for neuronal nicotinic acetylcholine
      receptors (nAChR) has been shown to bind with high affinity to the rodent and
      avian alpha 4 beta 2 nAChR subtype. This subtype may represent a primary
      molecular target for some of the beneficial central nervous system effects i.e.,
      cognitive enhancement, anxiolysis, analgesia, neuroprotection, of (-)-nicotine
      and related ligands. However, a detailed study of the human alpha 4 beta 2
      subunit combination has not yet been reported. In this study, we stably
      coexpressed the human neuronal alpha 4 and beta 2 nAChR subunits in human
      embryonic kidney (HEK) 293 cells and studied its pharmacological and regulatory
      properties. [3H]Cytisine bound to stably transfected cells with high affinity (KD
      value, 0.2 +/- 0.04 nM) and with a Bmax value of 1359 +/- 91 fmol/mg protein. A
      good correlation (r = 0.98) was observed between binding affinities in
      transfected cells and in native neuronal preparations for a series of nAChR
      ligands. 86Rb+ efflux studies showed that stably transfected cells express
      functional ion channels that are sensitive to blockade by dihydro-beta
      erythroidine. (+/-)-Epibatidine, (-)-nicotine, 1,1-dimethyl-4-phenylpiperazinium,
      (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole (ABT-418), acetylcholine and (
      )-cytisine stimulated 86Rb+ efflux with EC50 values of 0.02, 3.9, 2.5, 10, 44 and
      38 microM, respectively. Treatment of transfected cells with (-)-nicotine for 7
      days led to a significant increase in the density of [3H](-)-cytisine binding
      sites (EC50 = 0.56 microM) and a significant enhancement in the sensitivity of
      ACh. Specific binding or (-)-nicotine-evoked cation efflux was not detected in
      untransfected cells. Analysis of total cellular RNA from transfected, but not
      untransfected cells, showed the expected fragment sizes corresponding to the
      human alpha 4 and beta 2 subunit mRNA. These results demonstrate that stable
      expression of the human alpha 4 beta 2 nAChR subunit combination can give rise to
      functional ion channels that bind [3H](-)-cytisine with high affinity, exhibit
      homologous regulation and evoke agonist-induced cation flux with pharmacological
      properties consistent with native neuronal alpha 4 beta 2 nAChR.

PMID- 8558446
TI  - Biological and biochemical anti-human immunodeficiency virus activity of UC 38, a
      new non-nucleoside reverse transcriptase inhibitor.
AB  - UC 38, a simple analog of oxathiin carboxanilide, UC 84, lacking the oxathiin
      ring, was found to be a potent inhibitor of human immunodeficiency virus (HIV)-1
      induced cell killing and HIV replication in a variety of human cell lines, as
      well as in human peripheral blood lymphocytes and macrophages. UC 38 was active
      against a wide range of biologically diverse laboratory and clinical strains of
      HIV-1. However, UC 38 was inactive against HIV-2 and both nevirapine- and
      pyridinone-resistant strains of HIV-1. UC 38 selectively inhibited HIV-1 reverse
      transcriptase (RT), but not HIV-2 RT. Combination of UC 38 with 3'-azido-3'
      deoxythymidine synergistically inhibited HIV-induced cell killing. An HIV-1
      isolate resistant to UC 38 was selected in cell culture, and the mutations in the
      RT nucleotide sequences were determined. Comparison with the wild-type RT
      sequence revealed an amino acid change at position 181 (Tyr to Cys). The UC 38
      resistant virus was found to be cross-resistant to a variety of structurally
      diverse non-nucleoside RT inhibitors. UC 38 was susceptible to rapid degradation
      in vitro and in vivo; yet, nontoxic in vivo concentrations of UC 38 many-fold in
      excess of the in vitro effective concentrations could be achieved and maintained
      after s.c. or p.o. administration in hamsters. These results establish UC 38 as a
      new chemotype within the general class of HIV-1-specific RT inhibitors. The
      favorable physical characteristics, lack of toxicity, potency and bioavailability
      of UC 38 may make it a candidate for combination chemotherapy of acquired immune
      deficiency syndrome.

PMID- 8558447
TI  - Determination of Km for oxygen of nitric oxide synthase isoforms.
AB  - Biosynthesis of nitric oxide (NO) requires L-arginine and molecular oxygen.
      Although the apparent Km values for L-arginine of NO synthase isoforms have been
      reported, the apparent Km values for oxygen are unknown. Low oxygen tension has
      been shown to attenuate NO synthase activity and NO-dependent vascular
      relaxation. We investigated the effect of different concentrations of oxygen on
      NO synthase activity of bovine brain, cultured bovine aortic endothelial cells
      and RAW 264.7 macrophages. The apparent Km values for oxygen were 23.2 +/- 2.8,
      7.7 +/- 1.6 and 6.3 +/- 0.9 microM for the brain, endothelial and macrophage NO
      synthases, respectively. This suggests that pathophysiological conditions
      involving a decrease in tissue oxygen concentration may attenuate NO production.

PMID- 8558448
TI  - Regulation of CREB expression: in vivo evidence for a functional role in morphine
      action in the nucleus accumbens.
AB  - Previous work has shown that chronic opiate administration regulates protein
      components of the cAMP signaling pathway, specifically in the nucleus accumbens
      (NAc), a brain region implicated in the reinforcing properties of opiates, and
      that such adaptations may contribute to changes in reinforcement mechanisms that
      characterize opiate addiction. In the present study, we examined a possible role
      for the transcription factor cAMP response element-binding protein (CREB) in
      mediating these long-term effects of opiates in the NAc. Chronic, but not acute,
      morphine administration was found to decrease levels of CREB immunoreactivity in
      the NAc, an effect not seen in other brain regions studied. The functional
      significance of this CREB down-regulation was then investigated by the use of an
      anti-sense oligonucleotide strategy that produces a specific and sustained
      decrease in CREB levels in the NAc, without detectable toxicity. It was found
      that the antisense oligonucleotide-induced reduction in CREB levels mimicked the
      effect of morphine on certain, but not all, cAMP pathway proteins in this brain
      region, whereas a large number of other signal transduction proteins tested were
      unaffected by this treatment. Our results support a role for CREB in
      autoregulation of the cAMP pathway in the nervous system, as well as in mediating
      some of the effects of morphine on this signaling pathway in the NAc.

PMID- 8558449
TI  - The Chinese herbal remedy, T2, inhibits mitogen-induced cytokine gene
      transcription by T cells, but not initial signal transduction.
AB  - T2, an extract of Tripterygium wilfordii Hook F, has been reported to be
      effective in the treatment of a variety of autoimmune diseases, including
      rheumatoid arthritis. Previous studies have shown that T2 inhibited mitogen- or
      antigen-induced proliferation of human peripheral blood T cells and B cells, IL-2
      production by T cells and Ig production by B cells. In contrast, T2 did not
      affect monocyte functions, such as IL-1 production and antigen presentation. The
      current studies sought to localize the immunosuppressive action of T2 more
      precisely. Results show that T2 prevented [3H]-uridine uptake by mitogen
      stimulated T cells and arrested them in the early GI phase of the cell cycle. The
      inhibitory effects of T2 could be partially overcome by costimulating PHA
      activated T cells with PMA and completely nullified by costimulation with PMA
      plus a monoclonal antibody to CD28. Moreover, T2 had no effect on expression of
      IL-2R or the transferrin receptor (CD71), but inhibited production of a number of
      cytokines, including IL-2 and IFN-gamma by activated T cells. T2 suppressed IL-2
      mRNA levels, but not IL-2R mRNA levels, in activated T cells. T2-mediated
      inhibition reflected suppression of IL-2 gene transcription as indicated by
      suppression of the expression of a reporter gene driven by the IL-2 promoter. T2
      had little inhibitory effect on either IL-2 gene expression or cell cycle
      progression when added after initial mitogenic stimulation, indicating that an
      early step in the cascade of activation events was inhibited. However, initial
      activation events including protein tyrosine phosphorylation, the generation of
      diacylglycerol, IP3, and the translocation of protein kinase C were not inhibited
      by T2. Moreover, T2 did not inhibit the phosphatase activity of calcineurin.
      These results have localized the effect of T2 to a step in the T cell activation
      cascade after initial second messenger generation, tyrosine phosphorylation and
      protein kinase activation, but before IL-2 gene transcription.

PMID- 8558450
TI  - Comparative properties of a technetium-99m-labeled single-stranded natural DNA
      and a phosphorothioate derivative in vitro and in mice.
AB  - Oligonucleotides, particularly single stranded, may ultimately be of considerable
      use as radiopharmaceuticals. We have compared a synthetic 22-base single-stranded
      phosphodiester DNA with its phosphorothioate analog after both were radiolabeled
      with 99mTc via the hydrazino nicotinamide chelator. Whole body clearance of the
      label in mice was much slower when introduced on the phosphorothioate (30% vs.
      75% clearance at 6 hr) because of immediate and persistent accumulation in liver
      (47% vs. 2% injected dose/g at 4 hr). The label in both cases was present in
      urine primarily on low molecular weight catabolites. High-performance liquid
      chromatography analysis of 37 degrees C serum incubates showed serum protein
      binding of 99mTc in both cases (about 100% bound at 24 hr) but to different
      proteins. Different behavior with respect to protein binding was also observed in
      the analysis of liver and kidney homogenates: the phosphodiester label was almost
      quantitatively converted to lower molecular weight catabolites after only 15 min,
      whereas the phosphorothioate label was primarily on proteins. The rapid digestion
      of the phosphodiester by nucleases was not observed, probably because protein
      binding of the labeled oligonucleotides stabilized against degradation. Thus the
      phosphodiester DNA may be the preferred 99mTc-labeled oligonucleotide in certain
      circumstances to avoid the high and persistent liver uptake observed with the
      phosphorothioate DNA.

PMID- 8558451
TI  - Myocardial protection by the leukotriene synthesis inhibitor BAY X1005:
      importance of transcellular biosynthesis of cysteinyl-leukotrienes.
AB  - Perfusion of the isolated rabbit heart with 5 x 10(6) human polymorphonuclear
      leukocytes, under recirculating conditions (50 ml), and challenge with A-23187
      (0.5 microM) caused an increase in coronary perfusion pressure (from a
      prechallenge value of 46 +/- 1.1 to 176.2 +/- 29.7 mm Hg, 30 min after challenge,
      n = 6-4), which was linearly correlated (P < .006) with formation of cysteinyl
      leukotrienes (29.7 +/- 7.3 pmol/ml, 30 min after challenge). Pretreatment with
      the leukotriene synthesis inhibitor BAY X1005 (1 microM) (n = 6) resulted in
      significant protection against the increase in coronary perfusion pressure (76.7
      +/- 12.8 mm Hg, 30 min after challenge) and in almost complete inhibition of
      sulfidopeptide leukotriene synthesis (3.2 +/- 1.7 pmol/ml, 30 min after
      challenge). In in vivo experiments, ligation of the left anterior descending
      coronary artery in the rabbit (n = 10) resulted in acute myocardial infarction
      marked by a mortality rate of 60% compared with sham-operated animals (n = 10).
      Intravenous treatment of the rabbits with BAY X1005 (10 mg/kg/h, for 2 h) (n =
      10) markedly reduced the mortality rate (20%), protected the rabbits against the
      marked electrocardiogram derangement and abolished the significant increase in
      plasma creatine phosphokinase activity and cardiac tissue myeloperoxidase
      activity induced by coronary artery ligation. BAY X1005 exerts a significant
      cardioprotection and suggests that specific leukotriene synthesis inhibitors may
      lead to innovative therapy in myocardial ischemia.

PMID- 8558452
TI  - The effects of clomipramine on the excitatory action of ethanol on dopaminergic
      neurons of the ventral tegmental area in vitro.
AB  - Dopaminergic neurons of the ventral tegmental area (VTA) are important in the
      mediation of the rewarding properties of drugs of abuse such as ethanol. We have
      demonstrated in electrophysiological experiments in brain slices that serotonin
      potentiates the excitatory effect of ethanol on putative dopaminergic neurons of
      the VTA. Inasmuch as serotonin reuptake inhibitors have been shown to reduce
      ethanol intake in clinical studies, we investigated the effect of two serotonin
      reuptake inhibitors, clomipramine and zimelidine, on ethanol-induced excitation
      of VTA neurons recorded in vitro. Although zimelidine did potentiate ethanol
      induced excitation in some neurons, on average, the effect of zimelidine was not
      significant. Significant potentiation of ethanol excitation was seen with 500 nM
      clomipramine, but not at higher or lower concentrations. In addition,
      clomipramine also enhanced the potentiation produced by low concentrations of
      serotonin. The lack of potentiation of ethanol excitation seen with application
      of higher concentrations of clomipramine could not be explained by inhibition of
      reuptake of norepinephrine or dopamine, and is probably due to blockade of 5-HT2
      receptors by these higher concentrations of clomipramine. These results may have
      some implications for the development of serotonergic drugs, including serotonin
      uptake inhibitors, for the treatment of alcoholism.

PMID- 8558453
TI  - Inhibition of N-methyl-D-aspartate glutamate receptor subunit expression by
      antisense oligonucleotides reveals their role in striatal motor regulation.
AB  - N-methyl-D-aspartate (NMDA) glutamate receptors have an established role in the
      regulation of motor behavior by the basal ganglia. Recent studies have revealed
      that NMDA receptors are heteromeric assemblies of structurally related subunits
      from two families: NMDAR1, which is required for channel activity, and NMDAR2A-D,
      which modulate the properties of the channels. In the rat, the NMDA receptor
      subunits exhibit anatomically restricted patterns of expression, so that each
      component of the basal ganglia has a distinct NMDA receptor subunit mRNA
      phenotype. We have used in vivo intrastriatal injection of synthetic antisense
      oligodeoxynucleotides (ODNs) to examine the roles of particular NMDA receptor
      subunits in the regulation of motor behavior in rats. Injection of 15 nmol of a
      20-mer ODN targeted to the NMDAR1 subunit induced spontaneous ipsilateral
      rotation. Smaller doses of NMDAR1 antisense ODN did not lead to spontaneous
      rotation, but prominent ipsilateral rotation was observed after systemic
      administration of D-amphetamine. An antisense ODN to NMDAR2A was also effective
      in eliciting amphetamine-inducible rotation, although the magnitude of the effect
      was less than that seen with NMDAR1, whereas ODNs targeted to NMDAR2B, NMDAR2C
      and an NMDAR1 sense strand ODN had no effect on behavior. In situ hybridization
      demonstrated that injection of the NMDAR1, NMDAR2A or NMDAR2B antisense ODNs
      produced specific reductions in target mRNA signal intensity in the injected
      striatum. After NMDAR1 antisense ODN injection, striatal binding of 3H-glutamate
      target mRNA signal intensity in the injected striatum. After NMDAR1 antisense ODN
      injection, striatal binding of 3H-glutamate to NMDA sites was not altered,
      although strychnine-insensitive 3H-glycine binding sites exhibited a small but
      significant reduction. These observations suggest that NMDA receptor complexes
      containing NMDAR1 and, to a lesser extent, NMDAR2A subunits play particularly
      important roles in the regulation of motor behavior by neostriatal neurons.

PMID- 8558454
TI  - Roxindole: psychopharmacological profile of a dopamine D2 autoreceptor agonist.
AB  - The putative, selective dopamine (DA) dopamine-2 autoreceptor agonist roxindole,
      which also exhibits serotonin-1A-agonistic and 5-hydroxytryptamine reuptake
      inhibiting properties, was examined for its behavioral effects in rats and mice.
      Roxindole inhibited apomorphine-induced climbing in mice and stereotyped behavior
      in rats with ED50 values of 1.4 mg/kg s.c. and 0.65 mg/kg s.c., respectively, and
      inhibited conditioned avoidance response in rats (ED50 = 1.5 mg/kg s.c.). Thus
      roxindole showed a profile resembling those of the classical antipsychotic
      haloperidol and the atypical neuroleptic clozapine but differing from that of the
      DA autoreceptor agonist talipexole, which did not prevent apomorphine-induced
      behaviors. Unlike haloperidol, roxindole did not induce catalepsy in rats and
      mice. Investigations directed to the DA autoreceptor properties revealed that
      spontaneous motility of rats with normosensitive postsynaptic DA receptors was
      monophasically decreased by roxindole and talipexole, with a threshold dose of
      0.0625 mg/kg s.c. for both compounds. In reserpinized rats with presumably
      hypersensitive postsynaptic DA receptors, roxindole only partially reversed
      reserpine-induced hypomotility (threshold dose: 0.25 mg/kg); talipexole re
      established the activity level to that of normal rats. In contrast to
      apomorphine, roxindole did not induce and talipexole only marginally induced
      stereotyped behavior in normal rats. After administration of the DA dopamine-1
      agonist SKF 38393, talipexole induced stereotyped behavior in rats, which
      indicated its activity at postsynaptic dopamine-2 receptors. In contrast,
      roxindole did not induce stereotyped behavior in rats when co-administered with
      SKF 38393. These results indicate that, compared with talipexole, roxindole
      possesses a greater selectivity for DA autoreceptors.

PMID- 8558455
TI  - Effect of propionyl-L-carnitine on motor nerve conduction, autonomic cardiac
      function, and nerve blood flow in rats with streptozotocin-induced diabetes:
      comparison with an aldose reductase inhibitor.
AB  - The effects of propionyl-L-carnitine (PCAL) on caudal motor nerve conduction
      velocity, the coefficient of variation of the R-R interval on the
      electrocardiogram, and sciatic nerve blood flow were compared with those of [5-(3
      thienyl)tetrazol-1-yl] acetic acid monohydrate, an aldose reductase inhibitor, in
      rats with streptozotocin-induced diabetes. Diabetic control rats showed
      significantly delayed nerve conduction (P < .05), decreased R-R variability (P <
      .05) and reduced sciatic nerve blood flow (P < .05). Oral administration of PCAL
      (0.5 g/kg/day) and [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (0.05% in
      the diet: 60 mg/kg/day) for 8 weeks significantly improved both nerve conduction
      (P < .05) and R-R variability (P < .05) in diabetic rats, along with the
      normalization of sciatic nerve blood flow. PCAL treatment increased the nerve
      tissue levels of carnitine and myo-inositol and reduced the serum triglyceride
      level in diabetic rats. Our results suggests that PCAL could have therapeutic
      potential for the treatment of diabetic neuropathy.

PMID- 8558456
TI  - Novel anti-inflammatory compounds prevent CD11b/CD18, alpha M beta 2 (Mac-1)
      dependent neutrophil adhesion without blocking activation-induced changes in Mac
      1.
AB  - Leumedins are small organic molecules with anti-inflammatory properties in vivo.
      We report here that leumedins inhibit the CD11b/CD18 alpha M beta 2 (Mac-1)
      dependent adherence of neutrophils to serum proteins. The activation of
      neutrophils leading to adherence via Mac-1 is associated with an increase in cell
      surface Mac-1 level, and with an increased affinity of Mac-1 for adhesion
      partners. Inhibition of neutrophil adherence by leumedins does not require
      blocking the recruitment of Mac-1 from intracellular granules to the cell
      surface. Furthermore, leumedins do not block the expression on Mac-1 of the
      epitope for an "activation-specific" antibody (CBRM1/5). Time course studies show
      that leumedins inhibit adherence by targeting an event which occurs concurrently
      with changes in Mac-1 level and induction of the CBRM1/5 epitope. Therefore,
      leumedins block an unknown process which is permissive for Mac-1-dependent
      adherence.

PMID- 8558458
TI  - Biochemical and pharmacological characterization of multiple beta-endorphinergic
      antinociceptive systems in the rat periaqueductal gray.
AB  - Based on the differential abilities of the opioid antagonists naltrexone and D
      Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP) to antagonize the antinociceptive
      action of beta-endorphin and morphine in the rat periaqueducatal gray (PAG),
      three pharmacologically distinct mechanisms were determined to mediate the
      antinociceptive effect of beta-endorphin. Two of these mechanisms are unique to
      beta-endorphin, possess a high affinity for CTP and can be discriminated based on
      their differential sensitivity to naltrexone. The third mechanism displays
      characteristics common to that activated by morphine. The results of radioligand
      binding studies were consistent with these observations. [125I]-beta-Endorphin
      labeled a population of sites in the PAG which (compared to those labeled by
      [3H]morphine) displayed a significantly higher affinity for CTP. In addition, a
      naltrexone-insensitive binding component was identified in the [125I]-beta
      endorphin, but not [3H]morphine assays. Furthermore, comparable competitor
      affinities were determined across assays, suggesting an interaction of the
      radioligands with common PAG sites. A naltrexone-insensitive component to beta
      endorphin antinociception also was identified in studies which evaluated the
      ability of the antagonist to shift the beta-endorphin dose-response curve.
      Interestingly, the ability of low doses of CTP and naltrexone to inhibit
      increasing doses of beta-endorphin was described by a U-shaped dose effect curve.
      The response to low and high, but not intermediate, doses of beta-endorphin were
      antagonized by picomole doses of both antagonists. As there was no evidence for
      allosteric interactions between [125I]-beta-endorphin binding sites in the PAG,
      it appears that beta-endorphin also may activate pain facilitory mechanisms which
      counterbalance its overall antinociceptive effect.

PMID- 8558457
TI  - Corticotropin-releasing factor (CRF) antagonist [D-Phe12,Nle21,38,C alpha
      MeLeu37]CRF attenuates the acute actions of the highly potent cannabinoid
      receptor agonist HU-210 on defensive-withdrawal behavior in rats.
AB  - The present study evaluated the modulatory role of central corticotropin
      releasing factor (CRF) systems in the mediation of the effects of acute exposure
      to the brain cannabinoid receptor agonist HU-210 [3-(1,1-dimethylheptyl)-(-)-11
      hydroxy-delta 8-tetrahydrocannabinol] on defensive withdrawal behavior in male
      rats. The apparatus used for the defensive withdrawal test consisted of a small
      chamber, set on one side of a one-square meter open field. The actions of the
      potent CRF antagonist [D-Phe12,Nle21,38,C alpha MeLeu37]CRF (D-Phe CRF12-41) were
      examined on defensive behavior under both novel and familiar conditions. The
      acute i.c.v. administration of D-Phe CRF12-41 (0.2-5 micrograms/injection)
      antagonized the defensive behavior response to stressing conditions such as
      novelty or swim stress in field-habituated animals. The acute i.p. administration
      of HU-210 (4, 20 and 100 micrograms/kg) produced a clear dose-dependent stress
      like effects in field-habituated animals, as reflected in the HU-210-induced
      increase in both the emergence latency and the mean time spent in the small
      chamber. The i.c.v. administration of 5 micrograms of D-Phe CRF12-41, 5 min
      before the administration of the cannabinoid prevented the stressing actions of
      HU-210 (20 micrograms/kg, but not 100 micrograms/kg). Acute administration of HU
      210 also induced a dose-dependent increase in plasma corticosterone levels which
      was not antagonized by pretreatment with 5 micrograms of D-Phe CRF12-41. The
      present study suggests a role of central CRF systems in the mediation of the
      anxiogenic effects of brain cannabinoid receptor agonists. This finding is
      consistent with a direct hypothalamic effect of cannabinoids on the activation of
      the pituitary-adrenal axis.

PMID- 8558459
TI  - The unusual binding properties of the endothelin receptor antagonist CGS 27830
      distinguishes receptor/agonist interactions.
AB  - CGS 27830 [meso-1,4-dihydro-5-methoxycarbonyl-2,6-dimethyl-4-(3- nitrophenyl)-3
      pyridine carboxylic acid anhydride] is a nonpeptidic, insurmountable, endothelin
      (ET) receptor antagonist with approximately 10- to 20-fold selectivity for ETA
      receptors. CGS 27830 exhibits unusual binding properties which depend on the
      receptor and ligand: standard saturation binding experiments (coincubation of
      membranes with ligand in the absence or presence of antagonist) suggest that CGS
      27830 is a competitive inhibitor of [125I]IRL 1620 binding to ETB receptors in
      rat cerebellar membranes (i.e., there was a change of apparent Kd with no change
      of maximum binding), but a noncompetitive inhibitor of [125I]IRL 1620 binding to
      ETB receptors in rat lung membranes (i.e., significant loss of total binding was
      observed). Although the antagonist appears to be a noncompetitive inhibitor of
      [125I]IRL 1620 binding to ETB receptors in rat lung membranes, CGS 27830 appears
      to be a competitive inhibitor of [125I]ET-1 binding to the same receptors as well
      as to ETA receptors in A7r5 cell membranes. Thus, CGS 27830 can distinguish
      [125I]IRL 1620 binding to ETB receptors in rat cerebellar and lung membranes, but
      not ET-1 binding to ETB receptors in these tissues. These unusual binding
      properties demonstrate that rat lung and cerebellum ETB receptors interact
      differently with IRL 1620 or ET-1.

PMID- 8558460
TI  - YM90K: pharmacological characterization as a selective and potent alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionate/kainate receptor antagonist.
AB  - We investigated the pharmacological properties and neuroprotective actions of a
      novel alpha-amino-3-hydroxy-5-methylisoxazole-y-propionate (AMPA)/kainate
      receptor antagonist, [6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione
      hydrochloride (YM90K); formerly YM900], in comparison with those of 2,3-dihydroxy
      6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX). YM90K selectively displaced [3H]
      AMPA binding (Ki = 0.084 microM) and was less potent in inhibiting [3H]-kainate
      (Ki = 2.2 microM), [3H]-L-glutamate (N-methyl-D-aspartate-sensitive site; Ki >
      100 microM) and [3H]-glycine (strychnine-insensitive site; Ki = 37 microM)
      binding to rat brain membranes. YM90K co-injected with AMPA or kainate into the
      rat striatum protected cholinergic neurons against AMPA- or kainate-induced
      neurotoxicity. YM90K showed potent suppressive activity against audiogenic
      seizure in DBA/2 mice; ED50 values of YM90K and NBQX against tonic seizure were
      2.54 and 7.17 mg/kg (i.p.), respectively. The duration of the anticonvulsant
      effects of YM90K and NBQX was 30 min, indicating that both compounds possess
      short action. In a global ischemia model, YM90K (15 mg/kg i.p. x 3), NBQX (30
      mg/kg i.p. x 3) and CNQX (60 mg/kg i.p. x 3) significantly prevented the delayed
      neuronal death in the hippocampal CA1 region in Mongolian gerbils when
      administered 1 h after 5-min ischemia. In addition, the therapeutic time window
      for the neuroprotective effect of YM90K (30 mg/kg i.p. x 3) was 6 h. In a focal
      ischemia model, YM90K (30 mg/kg i.v. bolus+10 mg/kg/h for 4 h) reduced the volume
      of ischemic damage in the cerebral cortex in F344 rats. Thus, YM90K was shown to
      be a potent and selective antagonist for AMPA/kainate receptors in vitro and in
      vivo. This compound may provide a therapeutic effect in various neurodegenerative
      disorders such as ischemic stroke in which glutamate neurotoxicity is thought to
      play a critical role in neuronal damage.

PMID- 8558461
TI  - A novel P1 purinoceptor activates an outward K+ current in follicular oocytes of
      Xenopus laevis.
AB  - Follicular oocytes of Xenopus laevis possess P1 purinoceptors where, seemingly,
      both adenosine (Ado) and ATP are agonists. The basis of ATP agonism at this P1
      purinoceptor was investigated using electrophysiological and biochemical
      procedures. Ado and ATP activated an outward K+ current that reversed at -90 mV,
      was reduced by TEA and was inhibited by theophylline and 8-(p-sulphophenyl)
      theophylline but not by suramin. Outward K+ current to ATP and Ado also was
      inhibited by alpha, beta-methylene ATP. The affinity constants for Ado and ATP
      were identical, although ATP was a partial agonist. The potency order of
      nucleosides/nucleotides was 5'-N-ethylcarboxamide- adenosine > Ado > AMP > CGS
      21680 > beta, gamma-methylene ATP = ATP > ADP > R-N6 phenylisopropyl-adenosine,
      whereas 2-methylthioadenosine, ATP-O-(3-thiotriphosphate), uridine 5'
      triphosphate and alpha, beta-methylene ATP were inactive. Outward K+ current to
      ATP and nondegradable Ado analogs was unaffected by adenosine deaminase (although
      this enzyme prevented Ado agonism), which suggests that ATP is not broken down to
      Ado before activating K+ channels. The activity of oocyte ecto-ATPase was
      determined by HPLC analysis of ATP breakdown and by the production of inorganic
      phosphate. Oocyte ecto-ATPase showed a low rate of ATP hydrolysis and was
      incapable of generating sufficient Ado/AMP to activate P1 purinoceptors. The
      results show that a P1 purinoceptor that is not typical of other known Ado
      receptors (and ATP receptors) is present in the follicle cell layer of Xenopus
      oocytes and represents a novel purinoceptor subtype where both Ado and ATP are
      agonists in their own right.

PMID- 8558462
TI  - Proceedings of the scientific meeting of the Physiological Society. Oxford, 11-14
      July 1995. Abstracts.

PMID- 8558463
TI  - Phosphorylation of caldesmon by mitogen-activated protein kinase with no effect
      on Ca2+ sensitivity in rabbit smooth muscle.
AB  - 1. Recombinant, activated mitogen-activated protein kinase (3.3 microM; p42mapk)
      phosphorylated caldesmon in phasic (rabbit portal vein) and tonic (rabbit femoral
      artery) smooth muscle strips permeabilized with Triton X-100. 2. Phosphorylation
      of caldesmon by p42mapk neither induced contraction of relaxed smooth muscle nor
      affected the Ca2+ sensitivity of submaximally contracted permeabilized phasic or
      tonic smooth muscle.

PMID- 8558464
TI  - Residual Ca2+ channel current modulation by megestrol acetate via a G-protein
      alpha s-subunit in rat hypothalamic neurones.
AB  - 1. The inhibition of voltage-activated Ca2+ channel currents by the orally active
      progesterone derivative, megestrol acetate (MA), was examined in freshly
      dissociated rat ventromedial hypothalamic nucleus (VMN) neurones using the whole
      cell voltage-clamp technique with 10 mM Ba2+ as the charge carrier. 2. The steady
      state inhibition of the peak high-threshold Ca2+ channel current evoked by
      depolarization from -80 to -10 mV by MA increased in a concentration-dependent
      fashion. MA inhibited a fraction of the whole-cell Ca2+ channel current while
      progesterone had no effect on the peak Ca2+ channel current (7% at 10 microM).
      The low-threshold Ca2+ (T-type) current, evoked from -100 to -30 mV, was
      unaffected by MA. 3. Intracellular dialysis with MA had no effect on the Ca2+
      channel current. Concomitant extracellular perfusion of MA showed normal
      inhibitory activity, suggesting that the MA binding site can only be accessed
      extracellularly. 4. The high-threshold Ca2+ channel current in VMN neurones was
      found to consist of four pharmacologically distinguishable components: an N-type
      current, an L-type current, a P-type current, and a residual current. MA had no
      effect on the N-, L- and P-type Ca2+ channel currents, but inhibited the residual
      current. 5. In neurones isolated from cholera toxin-treated animals, the MA
      induced inhibition of the Ca2+ channel current was significantly diminished,
      suggesting a G-protein alpha S-subunit involvement. 6. Treatment with antisense
      phosphothio-oligodeoxynucleotides to the G alpha S-subunit (antisense-G alpha S)
      significantly reduced the MA-induced inhibition of the Ca2+ channel current.
      Treatment with either sense-G alpha S or antisense-G alpha 11 had no effect,
      confirming a G alpha S-subunit involvement. 7. These results suggest that
      appetite enhancement induced by MA in cachectic patients may in part be due to a
      novel central nervous system action, that is, inhibition of a fraction of the
      whole-cell Ca2+ channel current to attenuate the firing of VMN neurones that may
      be involved in satiety mechanisms.

PMID- 8558465
TI  - Different spatial patterns of [Ca2+] increase caused by N- and L-type Ca2+
      channel activation in frog olfactory bulb neurones.
AB  - 1. The intracellular calcium concentration ([Ca2+]i) in cultured olfactory bulb
      neurones of Xenopus laevis tadpoles was imaged using the calcium indicator dyes
      fluo-3 and Fura Red as well as a laser scanning microscope. 2. Upon extracellular
      application of brief pulses of a solution with high potassium concentration (high
      [K+]o), an increase in [Ca2+]i occurred in all neurones observed. During the
      first 2 days in culture this increase was highest. At later stages (more than 2
      days in culture) the increase in [Ca2+]i was non-homogeneous and highest in the
      dendritic processes. 3. Nifedipine (10 microM) reduced the high [K+]o-induced
      increase in [Ca2+]i. The reduction was greatest in somata and proximal dendrites.
      4. With nifedipine in the bath, the high [K+]o-induced increase of [Ca2+]i was
      further reduced by the application of omega-conotoxin GVIA (1 microM). The omega
      conotoxin-sensitive Ca2+ influx occurred predominantly on dendritic processes. 5.
      Noradrenaline (NA), as well as the alpha 2-adrenergic receptor agonist clonidine,
      reduced the high [K+]o-induced increase of [Ca2+]i. This reduction occurred
      mainly on dendritic processes. 6. Our results suggest a highly non-homogeneous
      spatial distribution of voltage-gated Ca2+ channels in cultured olfactory bulb
      neurones. L-type channels were found mainly on somata and their density seemed to
      decrease on the dendrites with increasing distance from the soma. In contrast,
      nifedipine-insensitive N-type channels were mainly observed on dendrites and were
      blocked by omega-conotoxin. NA, as well as clonidine, markedly blocked Ca2+
      influx through dendritic N-type Ca2+ channels.

PMID- 8558466
TI  - Synaptic GABAA activation induces Ca2+ rise in pyramidal cells and interneurons
      from rat neonatal hippocampal slices.
AB  - 1. Changes in intracellular Ca2+ concentration ([Ca2+]i) induced by activation of
      GABAA receptors (synaptic stimulation or application of the GABAA agonist
      isoguvacine) were studied on pyramidal cells and interneurons from hippocampal
      slices of rats from two age groups (postnatal days (P) 2-5 and P12-13) using the
      fluorescent dye fluo-3 and a confocal laser scanning microscope. Cells were
      loaded with the dye either intracellularly, using patch pipettes containing fluo
      3 in the internal solution, or extracellularly, using pressure pulses applied to
      an extracellular pipette containing the permeant dye fluo-3 AM. 2. Interneurons
      and pyramidal cells from P2-5 slices loaded with fluo-3 AM responded by an
      increase in [Ca2+]i to isoguvacine and to glutamate, in contrast to cells from
      P12-13 slices which responded to glutamate but not to isoguvacine. 3. The
      isoguvacine-induced rise in [Ca2+]i was reversibly blocked by bath application of
      the GABAA receptor antagonist bicuculline (20 microM), suggesting the specific
      involvement of GABAA receptors. The sodium channel blocker tetrodotoxin (TTX, 1
      microM in the bath) did not prevent the isoguvacine-induced rise in [Ca2+]i. 4.
      The isoguvacine-induced rise in [Ca2+]i was reversibly blocked by bath
      application of the calcium channel blocker D600 (50 microM) suggesting the
      involvement of voltage-dependent Ca2+ channels. 5. Electrical stimulation of
      afferent fibres induced a transient increase in [Ca2+]i in neonatal pyramidal
      cells and interneurons (P5) loaded non-invasively with fluo-3 AM. This elevation
      of [Ca2+]i was reversibly blocked by bicuculline (20 microM) but not by APV (50
      microM) and CNQX (10 microM). 6. During simultaneous electrophysiological
      recording in the current-clamp mode and [Ca2+]i monitoring from P5 pyramidal
      cells, electrical stimulation of afferent fibres, in the presence of APV (50
      microM) and CNQX (10 microM), caused synaptic depolarization accompanied by a few
      action potentials and a transient increase in [Ca2+]i. In voltage clamp (-70 mV)
      however, there was no increase in [Ca2+]i following synaptic stimulation, showing
      that it is depolarization dependent. 7. Using a non-invasive method of [Ca2+]i
      monitoring, we demonstrate here that in neonatal (P2-5) hippocampus, GABA is an
      excitatory neurotransmitter which can cause an elevation of [Ca2+]i in
      interneurons and pyramidal cells via activation of voltage-dependent Ca2+
      channels. This action may underlie the trophic role of GABA in hippocampal
      development.

PMID- 8558467
TI  - The effects of caffeine on intracellular calcium, force and the rate of
      relaxation of mouse skeletal muscle.
AB  - 1. Intracellular calcium concentration ([Ca2+]i) and force were measured from
      isolated single fibres of mouse skeletal muscle. The effects of 5 mM caffeine on
      muscle fibres at rest and during short tetani were examined. 2. Caffeine
      increased tetanic tension and slowed the rate of relaxation. [Ca2+]i was
      increased in the presence of caffeine both in the resting muscle and during
      tetani. The time course of decline of [Ca2+]i after a tetanus is complex with a
      large, early, rapid phase followed by a smaller and slower phase. Caffeine
      accelerated the early phase but slowed the later phase. 3. The sensitivity of the
      myofibrillar proteins to Ca2+ measured in the intact fibre was increased in the
      presence of caffeine, confirming earlier findings on skinned muscle fibres. 4.
      Analysis of the late phase of the decline of [Ca2+]i after a tetanus provides
      information about the properties of the sarcoplasmic reticulum (SR) Ca2+ pump.
      Caffeine slowed the pump to 60-70% of the control value at a given [Ca2+]i but
      had no effect on the Ca2+ leak from the SR. 5. Analysis of relaxation made use of
      the Ca(2+)-derived force in which the [Ca2+]i during relaxation was converted to
      the Ca(2+)-derived force by means of the steady-state relation between [Ca2+]i
      and force. The Ca(2+)-derived force fell more slowly in the presence of caffeine
      but the lag between Ca(2+)-derived force and measured force was unaffected. Thus,
      the slowed relaxation was caused by changes in Ca2+ handling and not by slowed
      cross-bridge kinetics. 6. A model of the Ca2+ movements and force production of
      muscle was used to examine independently the effects of increased Ca2+
      sensitivity, slowing of the SR Ca2+ pump and increased SR Ca2+ permeability. The
      effects of caffeine on [Ca2+]i, tetanic force and relaxation could be explained
      by a combination of these three effects.

PMID- 8558468
TI  - Fast activation and inactivation of inositol trisphosphate-evoked Ca2+ release in
      rat cerebellar Purkinje neurones.
AB  - 1. Calcium release from stores via inositol trisphosphate (InsP3) activation of
      intracellular Ca2+ receptor-channels is thought to have a role in regulating the
      excitability of cerebellar Purkinje neurones. The kinetic characteristics of
      InsP3 receptor activation in Purkinje neurones are reported here. 2. InsP3 was
      applied by flash photolysis of caged InsP3 during whole-cell patch clamp. Ca2+
      flux into the cytosol was measured with a low-affinity fluorescent Ca2+ indicator
      and by activation of Ca(2+)-dependent membrane conductance. 3. InsP3 produced
      Ca2+ release from stores with an initial well-defined delay (mean, 85 ms at 10
      microM InsP3), which decreased to less than 20 ms at high InsP3 concentrations.
      4. The rate of rise of free [Ca2+], which provides a measure of Ca2+ efflux and
      InsP3 receptor activation, increased with increasing InsP3 concentration in each
      cell and had a high absolute value of up to 1400 microM s-1 at 40 microM InsP3.
      The period of fast efflux was brief, inactivating in 25 ms at low and in 9 ms at
      high InsP3 concentration. 5. Peak free [Ca2+] was high (mean, 23 microM with a
      pulse of 40 microM InsP3) and increased with InsP3 concentration up to 80 microM
      InsP3 tested here. 6. Experiments with a flash-released, stable 5-thio-InsP3
      confirm that the low InsP3 sensitivity of Purkinje neurones does not result from
      metabolism of InsP3. 7. The low functional affinity and fast activation by InsP3
      suggest a difference in InsP3 receptor properties from non-neuronal cells tested
      in the same way. The large Ca2+ efflux and high peak [Ca2] probably result from
      high InsP3 receptor-channel density. 8. Elevated cytosolic [Ca2+] produced by
      Ca2+ influx through plasmalemmal Ca2+ channels strongly suppressed InsP3-evoked
      Ca2+ release from stores. Rapid termination of InsP3-evoked efflux results mainly
      from inhibition by high [Ca2+]. 9. The fast InsP3 activation kinetics and rapid,
      strong inactivation by Ca2+ influx suggest that interactions between InsP3
      mediated and membrane Ca2+ signalling could occur on a time scale compatible with
      neuronal excitation.

PMID- 8558469
TI  - Receptor kinase-dependent desensitization of the muscarinic K+ current in rat
      atrial cells.
AB  - 1. Activity of rat atrial muscarinic K+ channels has been measured in five
      configurations of the patch clamp technique. 2. In configurations in which the
      normal intracellular solution was lost, the slow phase of desensitization (a slow
      decline of channel activity during an exposure to ACh) was much reduced (or
      absent) and deactivation (on wash-off of ACh) was slowed as compared with
      desensitization and deactivation in configurations in which normal intracellular
      solution was retained. This suggests that soluble intracellular regulators are
      involved in these processes. 3. When a G protein-coupled receptor kinase (GRK2)
      was applied to the cytoplasmic surface of conventional outside-out patches in the
      presence of ATP, the slow phase of desensitization was restored. In the absence
      of ATP, GRK2 failed to restore the slow phase. 4. It is concluded that (i) G
      protein-coupled receptor kinase dependent phosphorylation of the muscarinic
      receptor is responsible for the slow phase of desensitization and (ii) a soluble
      factor (such as a GTPase activating protein or 'GAP') is responsible for normal
      rapid deactivation.

PMID- 8558470
TI  - Volume regulation in a toad epithelial cell line: role of coactivation of K+ and
      Cl- channels.
AB  - 1. We have measured changes in cell volume, membrane potential and ionic currents
      in distal nephron A6 cells following a challenge with hypotonic solutions (HTS).
      2. The volume increase induced by HTS is compensated by a regulatory volume
      decrease (RVD), which is inhibited by both 5-nitro-2-(3-phenylpropylamino)
      benzoate (NPPB) and quinine. Quinine (500 microM) completely blocked RVD, whereas
      100 microM NPPB delayed and attenuated RVD. 3. The resting potential in A6 cells
      was -52.3 +/- 4.8 mV (n = 53), and shifted to -35.1 +/- 2.2 mV (n = 33) during
      HTS. 4. Resting membrane current in A6 cells was 0.35 +/- 0.12 pA pF-1 at -80 mV
      and 0.51 +/- 0.16 pA pF-1 at +80 mV (n = 5). During cell swelling these values
      increased to 11.5 +/- 1.1 and 29.3 +/- 2.8 pA pF-1 (n = 29), respectively. 5.
      Quinine (500 microM) completely blocked the HTS-activated current at -15 mV, the
      reversal potential for Cl- currents, but exerted only a small block at -100 mV
      (K+ equilibrium potential). NPPB (100 microM) inhibited the current at both
      potentials almost to the same extent. The HTS-induced net current reversed at -41
      +/- 2.5 mV (n = 15), which is close to the measured resting potential during HTS.
      6. The quinine-insensitive current reversed near the Cl- equilibrium potential.
      The quinine-sensitive current reversed near the K+ equilibrium potential. The
      respective conductances activated by HTS at the zero-current potential were 2.1
      +/- 0.7 nS for K+ and 5.2 +/- 1.3 nS for Cl- (n = 15). 7. Single channel analysis
      unveiled activation of at least two different channels during HTS. A 36 pS
      channel reversing at the Cl- equilibrium potential showed increased open
      probability at depolarized potentials. HTS also activated a K+ channel with a 29
      pS conductance in high-K+ extracellular solutions (130 mM) or 12 pS in 2.5 mM K+.
      8. This coactivation of K+ and Cl- channels shifts the membrane potential towards
      a value between EK and ECl (the reversal potentials for K+ and Cl-), where a net
      efflux of Cl- (Cl- inward current) and K+ (K+ outward current) under zero-current
      conditions occurs. Block of either the K+ or the Cl- conductance will shift the
      zero-current potential towards the equilibrium potential of the unblocked
      channel, preventing net efflux of osmolytes and RVD. This coactivation of K+ and
      Cl- currents causes a shift of osmolytes out of the cells, which almost
      completely accounts for the observed RVD.

PMID- 8558471
TI  - Activation of the plasma membrane chloride channel by protein kinase C in
      isolated guinea-pig hepatocytes.
AB  - 1. To assess the nature of the underlying mechanism of noradrenaline-induced
      increase of Cl- conductances in hepatocytes, macroscopic and unitary currents
      through noradrenaline-induced Cl- channels were examined in enzymatically
      isolated guinea-pig hepatocytes using whole-cell, cell-attached and excised
      inside-out configurations of the patch-clamp technique. 2. When K+ conductances
      were blocked and the intracellular Ca2+ concentration ([Ca2+]i) was set at 0.1
      microM, bath application of noradrenaline activated the time-independent membrane
      currents under whole-cell voltage-clamp conditions. The current was similarly
      activated by phorbol ester (PMA), an activator of protein kinase C (PKC), while a
      specific protein kinase C inhibitor, H-9, reversed PMA activation of the current.
      The inactive phorbol ester, 4 alpha-phorbol 12-myristate, 13-acetate (alpha PMA),
      failed to activate the channel. 3. The reversal potential of the PMA-activated
      current shifted by approximately 60 mV per 10-fold change in the external Cl-
      concentration, indicating that the current was Cl- selective. Bath application of
      4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) partially inhibited
      both the noradrenaline- and PMA-induced currents. 4. In single channel recordings
      from cell-attached patches, bath application of noradrenaline or PMA induced
      unitary current activity, the averaged slope conductance of which was 10.1 +/-
      1.5 pS (mean +/- S.D.; n = 12) in the noradrenaline-induced current and 9.7 +/-
      1.3 pS (n = 7) in the PMA-induced current. The open time distribution was
      moderately well fitted by a single exponential function with mean open lifetime
      of 88.5 +/- 10.6 ms (n = 10), while at least two exponentials were required to
      fit the closed time distributions with a time constant for the fast component of
      24.4 +/- 5.8 ms (n = 10) and for the slow component of 316.9 +/- 49.2 ms (n =
      10). 5. Bath application of purified PKC to excised inside-out patches activated
      the channel. The PKC selective inhibitor, PKC(19-36), and DIDS inhibited the PKC
      activated channel. 6. These results suggest that PKC can phosphorylate the
      channel protein or a related structure leading to the activation of Cl- channels
      in guinea-pig hepatocytes.

PMID- 8558473
TI  - Non-selective cation current of guinea-pig endocardial endothelial cells.
AB  - 1. Endocardial endothelial (EE) cells, isolated by the enzymatic treatment of
      guinea-pig heart, were used for whole-cell voltage clamp experiments. 2. The
      inward rectifier K+ current was observed in about half of the experiments. The
      contribution of Ca(2+)-dependent K+ current to the resting membrane conductance
      was also suggested. 3. After the K+ conductances were suppressed, removal of
      external Na+ revealed an inward cation current (1.2 pA pF-1, at -45 mV), whose
      slope conductance was a saturable function of external Na+ concentration. When
      Na+ was totally replaced by various monovalent cations, the order of the membrane
      conductances was K+ > Rb+ > Cs+ > Na+ > Li+. 4. This basal non-selective cation
      current was blocked by either Gd3+ or La3+, and showed slight outward
      rectification. 5. Addition of 20 mM Ca2+ or Ba2+, but not Mg2+ or Mn2+, to the
      Na(+)-free solution, induced an inward current, indicating that this current
      possesses a significant Ca2+ permeability. 6. In approximately 15% of the
      experiments, ATP and histamine induced another type of non-selective cation
      current, which showed different ion selectivity (Na+ > K+, Cs+) and rectification
      (inward). 7. The basal non-selective cation current is responsible for both the
      low resting potential and the leak Ca2+ influx of EE cells.

PMID- 8558472
TI  - Patch-clamp analysis of glycine-induced currents in chick ciliary ganglion
      neurons.
AB  - 1. The whole-cell configuration of the patch-clamp technique was used to analyse
      currents induced by glycine in chick ciliary ganglion neurons freshly dissociated
      from 14- to 15-day-old embryos. 2. Application of glycine to cells voltage
      clamped at -60 mV induced inward currents in all neurons tested. Dose-response
      curves yielded an EC50 of about 50 microM. Similar responses were elicited by
      beta-alanine and taurine though higher concentrations were required. 3.
      Strychnine reversibly inhibited the glycine-induced responses. The effect was
      dose dependent with a half-maximal effect being obtained with 20 nM strychnine.
      4. Glycine-induced currents were inhibited by 100 microM Zn2+. The inhibition had
      slow rates of onset and recovery, in contrast to Zn2+ inhibition of GABA
      responses. Both bicuculline and d-tubocurarine inhibited glycine responses in a
      dose-dependent manner. 5. The steady-state I-V curve for glycine-induced currents
      was linear over the range -60 to +60 mV, but showed an outward rectification at
      very hyperpolarized membrane potentials. The reversal potential of glycine
      induced currents shifted with changes in intracellular chloride concentration in
      a manner expected for chloride-selective channels. 6. Expression of functional
      glycine receptors during development was examined at embryonic day 8 (E8), 11,
      14, and 18. The mean peak current was about 60-fold larger at E14 than at E8 and
      vastly exceeded changes in cell size. During the same period, responses to GABA
      increased only 2-fold in amplitude and correlated with changes in cell
      size.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8558474
TI  - Membrane properties of the granule cells of the islands of Calleja of the rat
      studied in vitro.
AB  - 1. Using patch-clamp techniques, we have studied granule neurones from the
      islands of Calleja in vitro: as isolated cells or as groups of varying numbers
      following enzymic digestion, or within untreated slices of approximately 100
      microns thickness. 2. Recordings were made with patch pipettes in conventional or
      nystatin-perforated whole-cell mode. Current-clamp recordings indicated that
      these granule cells are excitable and at resting potential produce irregular
      spontaneous activity. In voltage clamp the transient inward current underlying
      these action potentials could be evoked. This current had a threshold for
      activation of about -50 mV and was sensitive to TTX. In some cells a TTX
      resistant transient inward current was observed with a threshold for activation
      of about -70 mV. 3. Island of Calleja granule cells also exhibited outward
      currents. A rapidly activating transient current was observed that was resistant
      to TEA and sensitive to 4-AP, and therefore resembled IA. The current was half
      maximally activated at -6 mV and steady-state inactivation was half-complete at 
      65 mV. 4. More sustained outward currents were also observed. Although some cells
      appeared to express a Ca(2+)-activated K+ current, the most common finding was a
      rapidly activating, slowly inactivating, voltage-dependent K+ current that was
      sensitive to TEA and Ba2+. This current resembled M-current more than delayed
      rectifier but displayed a number of idiosyncratic kinetic properties. Chief
      amongst these was the accumulation of an inactivating process when the current
      was repeatedly evoked from potentials near the cells' resting value by voltage
      steps that by themselves produced no observable inactivation during the voltage
      command; this behaviour was similar to the 'C-terminal' inactivation exhibited by
      lymphocytes and certain expressed K+ channel clones (Kv1.3). 5. These results
      indicate that the granule cells of the islands of Calleja are excitable and
      contain a number of additional regulatory conductances. The implications of these
      findings in, and the usefulness of this preparation to, the elucidation of the
      function(s) of the islands of Calleja are discussed.

PMID- 8558475
TI  - Light adaptation and the rising phase of the flash photocurrent of salamander
      retinal rods.
AB  - 1. Both theory and analysis of photocurrents in retinal rods show that
      phosphodiesterase activity after a flash rises initially as a delayed ramp. 2.
      The effect of light adaptation on the flash-induced rise in phosphodiesterase
      activity deduced from photocurrent responses was investigated. 3. Background
      adaptation reduces the deduced rate of rise of phosphodiesterase activity. The
      effect is most prominent for bright backgrounds and moderate flashes. There is
      little reduction for bright flashes, even in bright backgrounds. There is no
      effect for weak backgrounds. 4. Light adaptation after bleaching visual pigment
      produces a reduction in the deduced rise of phosphodiesterase activity for all
      flashes. For bright flashes, the reduction is explained by the reduction in
      quantum catch. For moderate flashes, there is an extra reduction, similar to the
      reduction produced by the equivalent background. 5. The results provide support
      for the idea that a reduction in the amplification step of phototransduction
      functions as part of the mechanism of light adaptation in rods. The dependence on
      flash intensity of the background-induced reduction in phosphodiesterase
      activation could imply a feedback mechanism on the activation steps of
      phototransduction.

PMID- 8558476
TI  - Medullary-evoked EPSPs in neonatal rat sympathetic preganglionic neurones in
      vitro.
AB  - 1. Whole-cell patch clamp recordings were made from twenty-three sympathetic
      preganglionic neurones (SPNs) in the upper thoracic segments of a neonatal rat
      brainstem-spinal cord preparation to study their synaptic responses to
      stimulation of the rostral ventrolateral medulla (RVLM) and the receptors
      involved. 2. SPNs were identified by their antidromic activation following
      stimulation of a ventral root, their morphology and their location in the spinal
      cord. 3. Electrical stimulation within the RVLM elicited EPSPs in all SPNs tested
      (n = 23). These EPSPs consisted of one or more components that had different time
      courses, voltage relationships and pharmacological sensitivities. 4. All SPNs
      responded to RVLM stimulation with a constant-latency fast EPSP that increased in
      size as the membrane was hyperpolarized. This EPSP was reduced in amplitude by
      the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10-20
      microM). 5. In thirteen SPNs the response to RVLM stimulation was a complex EPSP
      consisting of a fast EPSP and a slow EPSP that either followed or summed with the
      fast EPSP. The amplitude of the slow EPSP was (i) either reduced in size or not
      affected as the membrane was hyperpolarized, and (ii) reduced by the NMDA
      receptor antagonist, D, L-2-amino-5-phosphonovaleric acid (50 microM). 6.
      Selective activation of neuronal cell bodies in the RVLM by chemical stimulation
      elicited slow depolarizations and increases in synaptic activity in SPNs. 7.
      These results provide evidence that an excitatory amino acid is involved in
      transmitting sympathoexcitatory drive from the RVLM, partly via a monosynaptic
      pathway. Both non-NMDA and NMDA receptors play a role in mediating this drive.

PMID- 8558477
TI  - Effects of divalent cations on exocytosis and endocytosis from single mouse
      pancreatic beta-cells.
AB  - 1. The effects of the divalent cations Ca2+, Ba2+ and Sr2+ on exocytosis and
      endocytosis from single isolated mouse pancreatic beta-cells were investigated by
      monitoring changes in cell capacitance. 2. The immediate increase in capacitance
      elicited by a single depolarization from -70 to +20 mV was dependent on the
      divalent cation species, with Ca2+ (8.2 +/- 1.1 fF pC-1) > Ba2+ (1.0 +/- 0.2 fF
      pC-1) > Sr2+ (0.7 +/- 0.2 fF pC-1) in perforated-patch recordings. 3. In Ba2+
      solutions alone there was subsequently an additional slow increase in capacitance
      (to 4.3 +/- 1.1 fF pC-1). This second phase of exocytosis was unaffected by
      preincubation with colcemid (20 microM, 45 min) or cytochalasin D (10 microM, 15
      min), suggesting that interaction of secretory granules with microtubules or
      microfilaments is not involved. 4. An increase in cell capacitance was elicited
      by depolarization in Ba2+ solutions when intracellular Ca2+ was buffered with 10
      mM EGTA. Infusion of the beta-cell with Ba2+ also stimulated exocytosis although
      the rate was much slower (1.1 +/- 0.2 fF s-1; 8 microM free Ba2+) than for Ca2+
      (39 +/- 5 fF s-1; 2 microM free Ca2+). These data indicate that Ba2+ does not
      evoke secretion by promoting Ca2+ release from internal stores. 5. The lower
      efficacy of Ba2+ in supporting exocytosis may be related to the fact that this
      cation does not activate calmodulin-dependent processes and the slow second phase
      of secretion may result from this ion being removed only slowly from the
      cytoplasm. 6. Endocytosis was faster in Sr2+ than in Ca2+ or Ba2+ solution, and
      the speed increased when the external concentration of all three divalent cation
      species was raised. The ability of Ba2+ to support endocytosis suggests
      calmodulin-dependent processes are not involved. These data suggest membrane
      retrieval is regulated differently from exocytosis in beta-cells.

PMID- 8558478
TI  - Concentration polarization of fluorescent dyes in rat descending colonic crypts:
      evidence of crypt fluid absorption.
AB  - 1. Using confocal microscopy, the rate of fluid absorption into isolated
      perifused descending rat colonic crypt lumens is estimated from the concentration
      polarization and distribution of fluorescein sulphonate (FS) and fluorescein
      isothiocyanate-dextran (FITC-dextran; molecular weight, 10,000) within the crypt
      lumens and pericryptal fluid. 2. The probe dyes enter the crypt via the luminal
      opening, are concentrated in the lumen, then escape into the pericryptal space
      via the paracellular spaces spanning the crypt wall. 3. FITC-dextran is maximally
      accumulated at a luminal depth of 60 microns to 5 times the concentration at the
      crypt opening (p < 0.001) and penetrates 150-200 microns along the lumen. FS is
      maximally accumulated within crypt lumen close to the opening. At crypt luminal
      depths 10-60 microns from the opening FS is accumulated by a factor of 1.5-2.0
      above that found in HgCl2-treated tissue (p < 0.001). 4. Dye enters the crypt
      lumen slowly from the basal side, but from this side does not accumulate above
      the bathing solution concentration. 5. HgCl2 (20 microM) or theophylline (10 mM)
      completely inhibit concentrative accumulation of FITC-dextran and FS within the
      crypts and pericryptal space (p < 0.001). 6. Computer simulation of the dye
      uptake indicates that the rate of water flow into the crypt luminal opening is 1
      x 10(-3) cm s-1 which is equivalent to 15 microliters (cm mucosa)-2 h-1.
      Approximately 75% of the fluid entering the crypt is abosrbed across the proximal
      50 microns of crypt wall as a consequence of the large osmotic pressure gradient
      between the pericryptal and crypt luminal solutions. A pericryptal diffusion
      barrier with lower permeability than that across the crypt wall is required to
      simulate dye accumulation in the pericryptal space. Differences between FITC
      dextran and FS accumulation are explained by the lower diffusion coefficient
      within the crypt lumen, and lower crypt wall permeability of FITC-dextran.

PMID- 8558479
TI  - The effects of systemic hypoxia on renal function in the anaesthetized rat.
AB  - 1. In rats anaesthetized with Saffan, renal function was monitored from the left
      kidney from the 5th minute of spontaneous breathing of 12% O2 for two 20 min
      periods and during air breathing before, between and after the hypoxic periods.
      Two groups of animals (I and II) were used, each group comprising two subgroups
      in which the left kidney was innervated or denervated, respectively; in Group II,
      renal perfusion pressure (RPP) was maintained during the 2nd hypoxic period by
      occl97uding the distal aorta. 2. In both subgroups of Group I, both hypoxic
      periods produced hyperventilation, arterial PO2 falling to approximately 50 mmHg.
      Concomitantly, mean arterial pressure (MABP) fell by similar extents
      (approximately 23%, from a baseline level of 140 mmHg during the 2nd hypoxic
      period). In the innervated subgroup, renal vascular conductance (RVC) increased,
      but glomerular filtration rate (GFR) fell (by 48 and 6%, respectively, during the
      2nd hypoxic period), while urine flow, absolute sodium excretion (UNaV) and
      fractional sodium excretion (FENa) fell (by 52, 63 and 61%, respectively).
      Baseline urine flow, UNaV and FENa were higher in the denervated subgroup, but
      hypoxia produced similar percentage changes from baseline in all variables. 3. In
      Group II, both subgroups showed similar changes during the 1st hypoxic period as
      the corresponding subgroups of Group I. However, during the 2nd hypoxic period
      when the fall in MABP was reduced to approximately 7%, the increase in RVC
      persisted only in the denervated subgroup; there was no significant change in
      GFR, urine flow, UNaV or FENa in either subgroup. 4. These results indicate that,
      in the rat, moderate hypoxia produces antidiuresis and antinatriuresis that are
      not dependent on the renal nerves, but are dependent on the hypoxia-induced fall
      in MABP. The fall in renal perfusion pressure (RPP) may directly determine renal
      function, but reflex influences upon the kidney initiated by, for example,
      arterial baroreceptor unloading, may play a role. The fall in GFR and increase in
      RVC, which persisted after denervation or when renal perfusion was controlled,
      implies a local dilatatory influence acting preferentially on the efferent
      arterioles.

PMID- 8558480
TI  - A study on rats of the effects of chronic hypoxia from birth on respiratory and
      cardiovascular responses evoked by acute hypoxia.
AB  - 1. Comparative studies were performed on eighteen rats 54 days old made
      chronically hypoxic from birth in an hypoxic chamber at 12% O2 (CHB), and in
      eight weight-matched control rats (NB, 42 days old); both CHB and NB rats were
      anaesthetized with Saffan. 2. In NB rats, breathing 12 or 8% O2 for 5 min induced
      a pattern of response comparable to that described in older rats (10-11 weeks
      old): an initial increase and secondary fall in minute volume (VE), a fall in
      arterial pressure (ABP), an increase in muscle vascular conductance, while
      cerebral blood flow (CBF) increased at the 1st minute in six animals and fell by
      the 5th minute in all animals. The adenosine receptor antagonist 8-phenyl
      theophylline (8-PT, 10 mg kg-1) reduced the secondary fall in VE, the fall in ABP
      and muscle vasodilatation, indicating they were partly mediated by adenosine. 3.
      In CHB rats breathing 12% O2, VE was higher (277 +/- 12 vs. 204 +/- 18 ml min-1),
      arterial partial pressures of O2 (45 +/- 2 vs. 88 +/- 3 mmHg), CO2 (32 +/- 1 vs.
      44 +/- 1 mmHg) and ABP (105 +/- 5 vs. 131 +/- 5 mmHg) were lower, while muscle
      vascular conductance was higher (0.08 +/- 0.01 vs. 0.03 +/- 0.01 ml min-1 mmHg-1)
      than in NB rats breathing air; these differences were reduced, but not abolished,
      when CHB rats acutely breathed air for 5 min. 4. In CHB rats, the smaller change
      from 12 to 8% O2 for 5 min evoked a similar pattern of response to that evoked by
      8% O2 in NB rats, except that heart rate (HR) and CBF decreased progressively.
      However, 8-PT increased baseline VE and reduced ABP in 12% O2 and reduced the
      secondary decrease in VE and HR evoked by 8% O2, but had no effect on the fall in
      ABP, or change in muscle vascular conductance. 5. We propose that in CHB rats (i)
      there is accentuation of the components of the response to acute hypoxia (the
      fall in ABP, HR and CBF) that form a positive feedback loop which promotes
      central ventilatory depression and (ii) that adenosine exerts a tonic inhibitory
      influence on VE and vasodilator influence in muscle and mediates the secondary
      fall in VE, but not the muscle vasodilation induced by acute hypoxia.

PMID- 8558482
TI  - The effect of voluntary contraction on cortico-cortical inhibition in human motor
      cortex.
AB  - 1. It has been previously shown that in a relaxed target muscle, at short
      interstimulus intervals (ISIs) (up to 6 ms) a conditioning subthreshold
      transcranial magnetic stimulus can cause suppression of the EMG response evoked
      by a magnetic test stimulus. At longer ISIs (7-15 ms) facilitation of the test
      response is seen. This type of inhibition has been termed ipsilateral cortico
      cortical inhibition. 2. The effect of a minimal tonic contraction on ipsilateral
      cortico-cortical inhibition has been investigated in the first dorsal
      interrosseous (FDI). 3. At short ISIs there was significantly less inhibition of
      the test response during the maintenance of minimal voluntary tonic contraction
      of the target muscle (FDI). 4. At longer ISIs (7-15 ms) there was significantly
      less facilitation of the test response during a tonic contraction than during
      relaxation. 5. Minimal activation of an ipsilateral proximal muscle (biceps) had
      no significant effect on the degree of inhibition seen in the relaxed target
      muscle (FDI). 6. We suggest that voluntary drive reduces the excitability of
      inhibitory circuits in cortical areas that project to the active muscle.

PMID- 8558481
TI  - Disynaptic group I excitation of synergist ankle extensor motoneurones during
      fictive locomotion in the cat.
AB  - 1. Intracellular recording from medial gastrocnemius (MG) motoneurones was used
      to examine postsynaptic potentials produced by electrical stimulation of the
      plantaris nerve at group I strength at rest and during fictive locomotion.
      Fictive locomotion was evoked by stimulation of the midbrain locomotor region
      (MLR) in decerebrate cats or in decerebrate, acute low-spinal cats by perineal
      stimulation following intravenous administration of clonidine and naloxone. 2. In
      both MLR and spinal fictive locomotor preparations, stimulation of plantaris
      nerve group I afferents at rest evoked short-latency (< 2 ms) IPSPs in MG
      motoneurones. During the extensor phase of MLR-evoked locomotion, the same
      stimulation produced short-latency (1.6-1.8 ms) EPSPs. Such latencies suggest
      mediation by one interneurone interposed between plantaris nerve group I
      afferents and MG motoneurones. Non-monosynaptic, short-latency excitation was not
      seen at rest nor during the flexion phase of the step cycle. 3. Group I EPSPs
      during the extensor phase of MLR-evoked locomotion were evoked by stimulation at
      intensities ranging from 1.4-2 times threshold (T). The effectiveness of
      stimulation intensities < 1.5 T suggests that activation of group II afferents is
      not required to evoke disynaptic excitation. Selective activation of group Ia
      afferents by stretches of the Achilles tendon also produced disynaptic EPSPs
      during extension. 4. During fictive locomotion in spinal animals pretreated with
      clonidine, short-latency group I EPSPs were not seen but group I IPSPs recorded
      at rest disappeared or were greatly attenuated. The failure of depolarizing
      current to reveal group I IPSPs suggests that fictive locomotion involves an
      inhibition of the inhibitory interneurones that operate at rest. In both
      clonidine-treated spinal and MLR preparations, trains of stimuli at group I
      strength evoked longer-latency and slowly rising potentials that were more
      prominent during the flexor phase of fictive locomotion. 5. These results show a
      reduction in short-latency group I inhibition of synergists in both MLR and
      clonidine-treated spinal preparations during fictive locomotion. In addition,
      activation of group I afferents evokes short-latency excitation of synergists
      during extension in the MLR preparation. Such excitatory reflexes activated by
      ankle extensor group Ia and Ib afferents may form an excitatory feedback system,
      reinforcing on-going extensor activity during the stance phase of the step cycle.

PMID- 8558483
TI  - Technetium 99m sulfur colloid scintigraphy to evaluate reticuloendothelial system
      function in dogs with portasystemic shunts.
AB  - In a retrospective study, technetium 99m sulfur colloid scintigraphy was used to
      evaluate reticuloendothelial system function in 61 dogs with single congenital
      and 40 dogs with multiple acquired portasystemic shunts. Whole body
      reticuloendothelial function was measured by calculating the plasma clearance
      rate constant from a dynamic study of liver uptake of 99mTc sulfur colloid.
      Relative liver, spleen, and lung uptake, and a ratio of hepatic:extrahepatic
      uptake were measured on static equilibrium images. Results were compared with
      those of a group of 26 normal dogs. Compared with values for the group of normal
      dogs, the plasma clearance rate constant, relative liver uptake, and
      hepatic:extrahepatic uptake ratio were significantly decreased, and relative
      spleen and lung uptake were significantly increased in dogs with portasystemic
      shunts (P < .0001). The only significant difference between dogs with single
      congenital versus multiple acquired shunts was that the relative splenic uptake
      was higher in the former group (P < .0002). Based on these results, we concluded
      that dogs with portasystemic shunts have significantly impaired
      reticuloendothelial function. The primary cause of this dysfunction is likely a
      reduction in effective liver blood flow. Increases in spleen and lung
      reticuloendothelial activity did occur, but only partially compensated for the
      reduction of liver reticuloendothelial activity. Possible mechanisms for the
      increased spleen and lung uptake are discussed.

PMID- 8558484
TI  - Lymphosarcoma in 10 New World Camelids.
AB  - We evaluated the medical information from 10 New World Camelids with
      lymphosarcoma. Additionally, tumor tissue from 5 animals was examined by electron
      microscopy for evidence of retroviral particles. Lymphosarcoma was the most
      common neoplasm of New World Camelids in our hospital. Both llamas and alpacas,
      from 4 months to 15 years of age, were affected. Emaciation (7 of 8) and palpable
      masses (9 of 10) were the most common physical examination abnormalities, and a
      left-shifted leukogram (7 of 7) and hypoalbuminemia (6 of 7) were the most
      characteristic clinicopathologic findings. Lymphosarcoma was diagnosed by lymph
      node aspirate (n = 2), biopsy (n = 2), peritoneal fluid analysis (n = 2), or
      necropsy (n = 4). The clinical course after recognition of the disease was
      usually short, with a median survival of 1 month (1 week to 3 months). Organs
      with neoplastic infiltrates commonly included lymph nodes (n = 8), liver (n = 8),
      kidneys (n = 6), and lungs (n = 5). No retroviral particles were detected
      ultrastructurally.

PMID- 8558485
TI  - Cytological analysis of bronchoalveolar lavage fluid in the diagnosis of
      spontaneous respiratory tract disease in dogs: a retrospective study.
AB  - Results of cytological analysis of bronchoalveolar lavage (BAL) fluid were
      compared with clinical diagnoses in dogs that presented with signs of respiratory
      disease to referral hospitals. Of 68 dogs in which a clinical diagnosis was
      possible, BAL cytological findings were considered definitive for the diagnosis
      in 17 cases (25%), supportive of the diagnosis in 34 cases (50%), and not helpful
      in 17 cases (25%). Findings were most often considered supportive of or
      definitive for the clinical diagnosis in dogs with alveolar or bronchial
      radiographic patterns, or the presence of pulmonary masses. BAL results among
      lung lobes differed in 23 of 63 dogs (37%) with diffuse radiographic patterns.
      Tracheal wash cytology differed from BAL fluid cytology in 45 of 66 dogs (68%).
      Bronchoalveolar lavage was a clinically useful procedure for the diagnostic
      evaluation of dogs with signs of respiratory disease.

PMID- 8558486
TI  - Cervical and thoracic vertebral malformation ("weak neck") in Colombia lambs.
AB  - The purpose of this study is to describe a developmental defect of the caudal
      cervical and cranial thoracic vertebrae in 11 purebred Colombia lambs. The lambs
      were either affected at birth, or developed the condition within the first 18
      days of age. Cervicothoracic kyphosis, with a compensatory cervical lordosis and
      ataxia were common; 8 lambs had abnormal head posture, characterized by inability
      to lift the head from the ground. One lamb had rigid head and neck, and had to
      move the entire body to look to the left or right. Neurological signs included
      ataxia, tetraparesis, diminished conscious proprioception, and increased patellar
      and triceps reflexes. One lamb had inspiratory stridor because of compression of
      the trachea in the area overlying the abnormal vertebrae (cervical vertebrae 6
      [C6] and 7 [C7]). Radiographic and pathological abnormalities included
      malalignment and malarticulation of the caudal cervical and cranial thoracic
      spine, rounded cranioventral margins in the bodies of vertebrae C7 and T1,
      wedging of the intervertebral disc spaces between C6 and T1 vertebrae, and
      hypoplasia of the dens. Pathological changes in the soft tissues included
      hypoplasia of the cervical epaxial and hypaxial musculature, with associated
      focal areas of myodegeneration. Mild Wallerian axonal degeneration, compatible
      with a mild cord compression syndrome, was found in 3 lambs in the
      cervicothoracic spinal cord adjacent to the vertebral anomalies. The
      concentrations of copper and selenium in blood, plasma, or tissues were normal in
      10 of 11 lambs. All but one of the lambs in which pedigree information was
      provided were genetically related. Siblings born as twins to 5 of the affected
      lambs were normal, but both lambs from one twin pregnancy were affected. Owners
      reported that breeding stock had been shared among the ranches. Because of the
      close familial relationships of the affected lambs, the condition is suspected to
      have a hereditary basis.

PMID- 8558487
TI  - Hepatic ultrasonography and pathological findings in dogs with hepatocutaneous
      syndrome: new concepts.
AB  - In dogs, hepatocutaneous syndrome (superficial necrolytic dermatitis) belongs to
      a group of syndromes in which cutaneous signs signal the presence of systemic
      disease. It is characterized by parakeratosis, superficial necrolysis, and
      basilar hyperplasia of the epidermis, in association with an unusual hepatopathy
      accompanied by certain metabolic derangements. Hepatocutaneous syndrome was
      diagnosed in 3 dogs on the basis of typical dermatologic changes and
      clinicopathologic findings. Hepatic ultrasonography revealed a hyperechoic
      network surrounding hypoechoic areas of parenchyma, resulting in a Swiss cheese
      like appearance. The ultrasonographic image corresponded to the pathological
      findings. The liver had a nodular appearance, both grossly and microscopically;
      this was attributed to collapse of the areas of parenchyma surrounding the
      nodules, rather than to the cirrhosis and/or nodular hyperplasia reported
      previously.

PMID- 8558488
TI  - Doppler ultrasonographic, oscillometric sphygmomanometric, and
      photoplethysmographic techniques for noninvasive blood pressure measurement in
      anesthetized cats.
AB  - Blood pressure (BP) measurements obtained using 3 indirect BP measuring
      instruments, a Doppler ultrasonic flowmeter, an oscillometric device, and a
      photoplethysmograph, were compared with direct arterial pressure measurements in
      11 anesthetized cats. The standard deviation of the differences (SDD) between
      direct and indirect pressure measurements were not significantly different from
      each other (P < .01), and ranged from 10.82 to 24.32 mm Hg. The high SDD values
      indicate that indirect BP estimates obtained with all these devices must be
      interpreted cautiously in individual patients. The mean errors (calculated as the
      sum of the differences between direct and indirect pressure measurements divided
      by the number of observations) of the 3 indirect devices were significantly
      different for systolic (SAP), diastolic (DAP), and mean (MAP) arterial pressures
      (P < .05). The Doppler and photoplethysmographic devices had the highest overall
      accuracy, as indicated by mean error values of less than 10 mm Hg. Correlation
      coefficients varied from .88 to .96 for the Doppler flowmeter, and from .85 to
      .94 for the photoplethysmograph; for both devices, the regression line slopes
      were close to unity. The Doppler flowmeter detected a pulse under all
      experimental conditions. The photoplethysmograph was also efficient in obtaining
      BP measurements, obtaining over 90% of SAP, DAP, and MAP readings attempted. The
      oscillometric device was the least accurate, with mean error values varying from
      10 to 22 mm Hg. Correlation coefficients were high (.90 to .94) for this device,
      but the slopes of the regression lines were 0.7 to 0.8, indicating a trend for
      increased error at higher BP. The oscillometric device tended to underestimate BP
      by increasing amounts as the BP increased. The oscillometric device was the least
      efficient device for obtaining BP measurements (P < .01).

PMID- 8558489
TI  - Hypoglycemia in four dogs with smooth muscle tumors.
AB  - Tumor-associated hypoglycemia has been reported in dogs with pancreatic beta-cell
      tumors, hepatic tumors, and, rarely, with other neoplasms. This article describes
      4 dogs with marked hypoglycemia associated with smooth muscle tumors (jejunal
      leiomyoma, gastric leiomyoma and leiomyosarcoma, and splenic leiomyosarcoma).
      Presenting clinical signs included grand mal seizures, lethargy, weakness,
      ataxia, and, in 1 dog, polyuria/polydipsia. The serum insulin concentration was
      low in 1 dog and normal in the other dog evaluated. Immunohistochemical staining
      for insulin was negative in the 4 tumors; the 3 tumors arising from the stomach
      and jejunum stained diffusely positive for glucagon. Blood glucose concentrations
      rapidly returned to normal after complete surgical resection of the tumors, and
      clinical signs associated with hypoglycemia resolved. Long-term follow-up
      available in 3 of the 4 dogs found no recurrence of clinical signs related to
      hypoglycemia at 15, 31, and 38 months after surgery, respectively.

PMID- 8558490
TI  - Balloon valvuloplasty of tricuspid stenosis in a Labrador retriever.

PMID- 8558491
TI  - Response to liposome-encapsulated doxorubicin (TLC D-99) in a dog with myeloma.

PMID- 8558492
TI  - Clinical vignette. Mucopolysaccharidosis VI in a miniature pinscher.

PMID- 8558493
TI  - Transfer of technetium from soil to paddy and upland rice.
AB  - Soil-plant transfer factors (concentration ratio between the plant and soil) of
      technetium in paddy and upland rice plants were obtained from laboratory
      experiments. The transfer factor is one of the most important parameters for
      environmental radiation dose assessment. Technetim tracer (95mTcO4-) was added to
      the soil prior to rice cultivation. The transfer factor of technetium for the
      hulled grains (brown rice) of paddy rice (< or = 0.0002) was much lower than for
      that of upland (0.021). The transfer factors for both types of hulled grains were
      much lower than in the leaves. The technetium decontamination rate from hulled
      grains by polishing was 34%, the percentage of the weight decrease being 12%. The
      concentration of technetium in the soil solution collected from the paddy rice
      soil (flooded conditions) decreased rapidly with time due to its adsorption on
      the soil. In the upland rice soil (non-flooded) solution, the decrease in the
      technetium concentration was fairly slow. The low transfer factors for the paddy
      rice plants could be explained by the immobilization of technetium in the flooded
      soil. The oxidation-reduction potentials (Eh) in the flooded soil decreased
      rapidly with time. We conclude that technetium tracer added as TcO4- to flooded
      soil is readily transformed to an insoluble form (e.g. TcO2) under the reducing
      conditions provided by flooding.

PMID- 8558494
TI  - Long term effects of prenatal exposure to low level gamma rays on spontaneous
      circadian motor activity of male mice.
AB  - The spontaneous circadian motor activity of first generation (F1) hybrid male
      C57BL/6xC3H mice irradiated with gamma rays on the 14th day of gestation was
      studied at the following ages: young (6-7 months), adult (12-13 months), and old
      (19-20 months). Doses were 0.1, 0.2, 0.5 or 1.0 Gy. A 12-hour day-night cycle was
      maintained with light on a at 6:00 hr. Spontaneous circadian motor activity was
      recorded with a capacitance-induction motility monitor for 48 consecutive hours.
      Activity was measured at 2-hour intervals, and the data stored on computer discs.
      The activity of the 1.0 Gy group recorded at 22:00 and 2:00 hr for young mice and
      at 2:00 hr for adult ones was significantly higher than that of the age-matched
      control group. Results suggest that male mice irradiated with 1.0 Gy at
      gestational day 14 show nocturnal hyperactivity in the young and adult stages.

PMID- 8558495
TI  - Analysis of mutations in the human HPRT gene induced by accelerated heavy-ion
      irradiation.
AB  - Multiplex PCR analysis of HPRT(-) mutations in human embryo (HE) cells induced by
      230 keV/microns carbon-ion irradiation showed no large deletion around the exon
      regions of the locus gene in contrast to the irradiations at different LETs. To
      identify these mutations, the sequence alterations in a cDNA of hprt gene were
      determined for 18 mutant clones in this study. Missing of exon 6 was the most
      frequent mutational event (10 clones), and missing of both exons 6 and 8 was next
      most frequent event (6 clones), then base substitutions (2 clones). These
      characteristics were not seen in a similar analysis of spontaneous mutations,
      which showed base substitution (5 clones), frameshift (2 clones), missing of both
      exons 2 and 3 (2 clones), and a single unidentified clone. Direct sequencing and
      restriction enzyme digestion of the genomic DNA of the mutants which showed
      missing of exons 6 and 8 in the cDNA, supports the possibility that they were
      induced by aberrant mRNA splicing.

PMID- 8558496
TI  - Whole-body retention and fetal uptake of 65Zn in pregnant mice fed a Zn-deficient
      diet.
AB  - Whole-body retention and fetal uptake of 65Zn under a Zn-deficient diet were
      studied in pregnant mice in the late gestational stage after a single oral
      administration of 65Zn. Whole-body retentions were much greater in mice given a
      Zn-deficient diet than in those given a Zn-normal diet. Accordingly, the amount
      of 65Zn transmitted to the offspring in utero was greater in the Zn-deficient
      diet group. In another experiment, fetal uptake of 65Zn in dams on gestation day
      17 was examined over a period of 24 hr after a single intravenous administration
      of 65Zn to the Zn-deficient and Zn-normal animals. There was no major difference
      in fetal uptake between the two groups, indicative that approximately a similar
      proportion of the 65Zn retained in the maternal body was transmitted to the in
      utero offspring in both groups.

PMID- 8558497
TI  - Lithium delays the radiation-induced apoptotic process in external granule cells
      of mouse cerebellum.
AB  - Proliferating cells of the external granular layer (EGL) in the developing
      cerebellum are highly sensitive to ionizing radiation. We examined the effect of
      lithium, an inhibitor of intracellular signaling, on the manifestation of
      radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma
      irradiation alone, or first were treated with lithium (10 mumol/g, SC) then given
      0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis
      at various times after treatment. Apoptotic cells increased rapidly, peaked
      (about 14%) 6 hr after irradiation, then decreased gradually to the control level
      by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis,
      the peak appearing at 12 hr. The disappearance of dead cells was delayed for
      about one day. The lithium concentration in the whole brain increased rapidly,
      being 30 micrograms/g at the time of irradiation and remaining at more than 40
      micrograms/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding
      to G proteins as well as phosphoinositide turnover. Of the variety of lesions
      induced by radiation, DNA double strand breaks are the most important source of
      cell lethality. The present findings, however, suggest that cyclic AMP-mediated
      and/or phosphoinositidemediated signaling systems regulate radiation-induced
      apoptosis.

PMID- 8558498
TI  - Augmentation of NO production and cytolytic activity of M phi obtained from mice
      irradiated with a low dose of gamma-rays.
AB  - The activation of macrophages (M phi) by low-dose irradiation (4cGy) was
      examined. The irradiated M phi were obtained from mice exposed to a low dose of
      gamma-rays. The addition of excess irradiated M phi suppressed more the
      concanavalin A-induced proliferation of splenocytes than that of unirradiated M
      phi. This was attributed to large nitric oxide (NO) production from irradiated M
      phi. In addition, low-dose irradiation augmented NO production and glucose
      consumption in M phi treated with interferon-gamma alone or interferon
      gamma/lipopolysaccharide. Furthermore, low-dose-irradiated M phi showed a higher
      cytolytic activity against P-815 mastocytoma cells than unirradiated M phi,
      indicating that the NO production was involved in the activity. On the other
      hand, the M phi irradiated with a low dose in vitro did not enhance the NO
      production. These findings suggest that whole-body irradiation with a low dose of
      gamma-rays activates M phi indirectly and consequently enhances NO production
      from M phi, by which the self-defense systems such as the tumoricidal activity
      will be augmented.

PMID- 8558499
TI  - Substituted 1,2-dihydrophthalazines: potent, selective, and noncompetitive
      inhibitors of the AMPA receptor.

PMID- 8558500
TI  - (2S,3S,5R)-2-(3,5-difluorophenyl)-3,5-dimethyl-2-morpholinol: a novel
      antidepressant agent and selective inhibitor of norepinephrine uptake.

PMID- 8558501
TI  - Two new criteria for choosing sample size in combinatorial chemistry.

PMID- 8558502
TI  - Potent, cell active, non-thiol tetrapeptide inhibitors of farnesyltransferase.
AB  - All previously reported CAAX-based farnesyltransferase inhibitors contain a thiol
      functionality. We report that attachment of the 4-imidazolyl group, via 1-, 2-,
      or 3-carbon alkyl or alkanoyl spacers, to Val-Tic-Met or tLeu-Tic-Gln provides
      potent FT inhibitors. (R*)-N-[[1,2,3,4-Tetrahydro-2-[N-[2-(1H-imidazol-4
      yl)ethyl] -L-valyl]-3-isoquinolinyl]carbonyl]-L-methionine ([imidazol- 4-yl
      ethyl]-Val-Tic-Met), with FT IC50 = 0.79 nM, displayed potent cell activity in
      the absence of prodrug formation (SAG EC50 = 3.8 muM).

PMID- 8558503
TI  - Synthesis and quantitative structure-activity relationship of a novel series of
      small conductance Ca(2+)-activated K+ channel blockers related to dequalinium.
AB  - The synthesis, pharmacological testing, and quantitative structure-activity
      relationship studies of a novel series of bisquinolinium small conductance Ca(2+)
      activated K+ channel blockers (23) related to dequalinium are described. In this
      series, two quinolinium rings are linked via the 4-position to an alpha, omega
      diamino alkylene chain and the ring N atom is quaternized with a methyl or benzyl
      group. The exocyclic N atom can be replaced by O, S, or CH2 but with some loss of
      potency. The quinoline groups do not have to be quaternized for blocking
      activity, as long as they are basic enough to be protonated at the site of
      action. For the quaternary compounds, there is considerable steric tolerance for
      the group R attached to the ring N atom of the quinoline; a benzyl group gave the
      optimum potency in this series. Moreover, and in contrast to previously reported
      results for dequalinium analogues, there is no correlation of activity to
      previously reported results for dequalinium analogues, there is no correlation of
      activity with N1 charge or EHOMO. On the other hand, a good correlation was
      obtained between the blocking potency of the compounds and ELUMO [pEMR = 1.16(+/
      0.26)ELUMO + 5.33(+/-01.29)(n = 11, r= 0.83, s = 0.243)]. It has been possible to
      combine this equation with the previously reported ELUMO correlation for a series
      of dequalinium analogues to include all the compounds of both series [pEMR =
      1.17(+/-0.15)ELUMO +5.33(+/-0.76)(n =24, r = 0.85, s = 0.249)]. A possible
      physical meaning for the ELUMO correlation based upon the principle of maximum
      hardness is discussed.

PMID- 8558504
TI  - 2-Carbomethoxy-3-(diarylmethoxy)-1 alpha H, 5 alpha H-tropane analogs: synthesis
      and inhibition of binding at the dopamine transporter and comparison with
      piperazines of the GBR series.
AB  - We recently reported a new class of tropanes, based on benztropine, that bind
      uniquely, in the S-configuration, to the dopamine transporter. We have now
      extended this series to evaluate the effects of substituents on the nitrogen and
      the diarylmethoxy group. Herein we have described the synthesis and biological
      evaluation of a series of 2-carbomethoxy-3-(diaryl-methoxy)-1 alpha H, 5 alpha H
      tropane (2-carbomethoxybenztropine) analogs. Examination of the binding data
      obtained for these compounds shows that while the 4,4'-difluoro compound is
      potent and selective for the dopamine transporter, introduction of larger groups
      such as 4,4'-dichloro, 4,4'- dibromo, 4,4'-diiodo, or 4,4'dimethyl on the 3
      diphenylmethoxy moiety reduces this potency. However, although introduction of
      only one group (e.g., 4-chloro, 4-bromo, 4-iodo, or 4-methyl) leads to a similar
      reduction of binding affinity, these monosubstituted 2-carbomethoxybenztropines
      are significantly more potent than the related disubstituted compounds. Finally,
      from the data for the N-substituted 2-carbomethoxybenztropine analogs, it is
      evident that steric bulk can be tolerated at the nitrogen site. A comparison of
      structure-activity relationship data for the tropanes, GBR analogs, and these
      benztropines indicates that the 2-carbomethoxybenztropine analogs may be more
      like the GBR analogs in their mode of binding to the dopamine transporter than
      like the tropanes. This conclusion supports the notion that the binding site for
      (-)-cocaine [and the (1R)-tropanes] may differ from of the 2
      carbomethoxybenztropine analogs.

PMID- 8558505
TI  - A comparative molecular field analysis study of N-benzylpiperidines as
      acetylcholinesterase inhibitors.
AB  - A series of 1-benzyl-4-[2-(N-benzoylamino)ethyl]piperidine derivatives and of N
      benzylpiperidine benzisoxazoles has been investigated using the comparative
      molecular field analysis (CoMFA) approach. These compounds have been found to
      inhibit the metabolic breakdown of the neurotransmitter acetylcholine (ACh) by
      the enzyme acetylcholinesterase (AChE) and hence alleviate memory deficits in
      patients with Alzheimer's Disease by potentiating cholinergic transmission.
      Development of the CoMFA model considered two separate alignments: (i) alignment
      I which emphasized the electrostatic fitting of the subject compounds and (ii)
      alignment II which emphasized their steric fitting. In addition, the inhibitor
      compounds were considered both as neutral species and as N-piperidine-protonated
      species. The resulting 3D-QSAR indicates a strong correlation between the
      inhibitory activity of these N-benzylpiperidines and the steric and electronic
      factors which modulate their biochemical activity. A CoMFA model with
      considerable predictive ability was obtained.

PMID- 8558506
TI  - A study of the active site of influenza virus sialidase: an approach to the
      rational design of novel anti-influenza drugs.
AB  - The development of sialidase inhibitor-based potential anti-influenza drugs using
      rational drug design techniques has been of recent interest. The present study
      details as investigation of the active site of influenza virus sialidase by using
      the program GRID in an attempt to design more potent inhibitors in the hope they
      will eventually lead to anti-influenza drugs. A number of different probes
      (amino, carboxy, hydroxy, methyl, etc) have been used in an effort to determine
      the functional groups most likely to improve the binding of the starting template
      2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en). The data have
      correctly predicted the binding regions for the carboxylate, acetamido (NH and
      methyl), and glycerol (OH) groups of N-acetylneuraminic acid. Moreover, the data
      suggest that the addition of certain functionalities (amino group) at the C-4
      position should enhance the overall binding.

PMID- 8558507
TI  - A novel, picomolar inhibitor of human immunodeficiency virus type 1 protease.
AB  - The design, synthesis, and molecular modeling studies of a novel series of
      azacyclic ureas, which are inhibitors of human immunodeficiency virus type 1 (HIV
      1) protease that incorporate different ligands for the S1', S2, and S2' substrate
      binding sites of HIV-1 protease are described. The synthesis of this series is
      highly flexible in the sense that the P1', P2, and P2' residues of the inhibitors
      can be changed independently. Molecular modeling studies on the phenyl ring of
      the P2 and P2' ligand suggested incorporation of hydrogen-bonding donor/acceptor
      groups at the 3' and 4-positions of the phenyl ring should increase binding
      potency. This led to the discovery of compound 7f (A-98881), which possesses high
      potency in the HIV-1 protease inhibition assay and the in vitro MT-4 cell culture
      assay (Ki = approximately 5 pM and EC50 = 0.002 microM). This compares well with
      the symmetrical cyclic urea 1 pioneered at DuPont Merck.

PMID- 8558508
TI  - Tetrahydrobenzothiophenone derivatives as a novel class of adenosine receptor
      antagonists.
AB  - A novel class of non-nitrogen-containing heterocycles, the
      tetrahydrobenzothiophenones, was found to bind to adenosine receptors as
      antagonists in the micromolar range. Affinity was determined in radioligand
      binding assays at rat brain A1 and A2a receptors. A structure-activity analysis
      indicated that a 3-thioether group is favored and affinity at A2a, but not at A1,
      receptors is highly dependent on this thioether substituent. A carboxylic acid
      derived substituent is required at the 1-position of the thiophene ring, with
      esters being more potent in binding at A1 receptors than the corresponding
      carboxyl hydrazide or carboxylic acid derivatives. The methyl (15) and ethyl (16)
      esters are about equipotent at A1 but not at A2a receptors. A 4-keto group on the
      saturated ring is favored for receptor affinity. Dimethyl substitution at the 6
      position of the saturated ring is allowed. One of the most potent derivatives was
      the nonselective compound ethyl 3-(benzylthio)-4-oxo-4,5,6,7-tetrahydrobenzo[c]
      thiophene-1-carboxylate (BTH4, 7; Figure 1), which antagonized adenosine agonist
      induced inhibition of adenylyl cyclase in rat adipocyte membranes with a KB value
      of 1.62 +/- 0.73 microM and adenosine agonist-induced stimulation of adenylyl
      cyclase in pheochromocytoma cell membranes with a KB value of 9.19 +/- 0.98
      microM. Displacement of radioligand binding by BTH4 (7) at cloned human A3
      receptors was negligible but one slightly A3 selective compound (11, 3.9-fold
      over A1 and >7.5-fold over A2a) was found. A 1-methylpropyl thioether (17) was 29
      fold selective for A1 and A2a receptors. BTH4 (7) alone, at 10 mg/kg, stimulated
      locomotor activity in mice but paradoxically acted, under certain circumstances,
      synergistically with an A1 selective agonist to depress locomotor activity. A
      pharmacophore model relating structural features of xanthine and non-xanthine
      adenosine antagonists to BTH4 (7) suggests a high degree of similarity in
      electrostatic surfaces, assuming that the thiophene ring superimposes the region
      of the uracil ring of xanthines.

PMID- 8558509
TI  - Syntheses and conformational analyses of glutamate analogs: 2-(2-carboxy-3
      substituted-cyclopropyl)glycines as useful probes for excitatory amino acid
      receptors.
AB  - An hypothesis that each subtype of glutamate receptors requires a specific
      conformation of L-glutamate for its selective activation was examined using the
      conformationally constrained analogs of L-glutamate, L-2-(2
      carboxycyclopropyl)glycines (CCGs), and L-2-[2-carboxy-3
      (methoxymethyl)cyclopropyl)glycines (MCGs). All MCG isomers were newly
      synthesized in a stereoselective manner via the common synthetic intermediate 5a
      starting with the oxazolidine aldehyde 1. The synthesis of the four MCG isomers
      was characterized by a stereoselective inversion of alpha-cyclopropyl acyl anion
      (e.g., from 10 to 11). The spectroscopic studies, in particular, pH vs J
      correlation experiments of CCGs and MCGs using 1H NMR and their molecular
      mechanics calculations, revealed that these analogs possessed an antiperiplanar
      conformation regarding the H-C2-C1'-H bond as a majority among the other possible
      rotamers in aqueous solution. The fact that each CCG and MCG exhibited potent and
      selective activities to the distinct types of glutamate receptors allowed us to
      extract an active conformation of L-glutamate. Thus, the conformational
      requirement of metabotropic glutamate receptors was speculated to be the anti
      anti conformation (aa-A) because the conformations of CCG-1 and cis and trans-MCG
      I, selective agonists of the receptors, closely mimicked the rotamer A of L
      glutamate. On the other hand, N-methyl-D-aspartate and kainate receptors,
      representative ionotropic glutamate receptors, would require glutamate g+g+
      rotamer E which was deduced from the conformation-activity relationship studies
      of the selective agonists CCG-IV, cis-MCG-IV, and trans-MCG-IV and the related
      analogs.

PMID- 8558510
TI  - Drug delivery systems: water soluble taxol 2'-poly(ethylene glycol) ester
      prodrugs-design and in vivo effectiveness.
AB  - Water soluble 2'-taxol poly(ethylene glycol) (PEG) esters have been synthesized
      and shown to function in vitro as prodrugs. However, in vivo experiments clearly
      establish that in order for these prodrugs to behave in a predictable fashion,
      the molecular weight of PEG must be of such magnitude so as to maintain a
      t1/2(circulation) > t1/2(hydrolysis). When PEG derivatives of molecular weight
      approximately 40 kDa were employed with paclitaxel, ca. 4% by weight of
      paclitaxel was carried by the water soluble prodrug form, and equivalent in vivo
      toxicity and increased life expectancy in the P388-treated mouse was observed. An
      effective method for prescreening prodrugs was found to be the acute murine
      lethality, which reflects the equivalency of the solubilized transport form and
      the native drug.

PMID- 8558511
TI  - Characterizations of the unusual dissociation properties of melanotropin peptides
      from the melanocortin receptor, hMC1R.
AB  - Variation in the degree of prolonged (residual) biological activity of the
      melanotropin peptides alpha-MSH (alpha-melanocyte-stimulating hormone, Ac-Ser-Tyr
      Met-Glu- His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) and the superpotent analogues
      [Nle4,DPhe7]alpha-MSH (MT-I) and Ac-[Nle4,Asp5,DPhe7,Lys10]alpha-MSH(4-10-NH2 (MT
      II) has stimulated considerable interest regarding this biological phenomena. We
      have examined the differences in their relative dissociation rates from the
      melanocortin receptor, hMC1R, to try and correlate peptide dissociation rates
      with the observations of prolonged biological activity. Interestingly, these
      studies revealed that alpha-MSH remained 25% bound, MT-I 65% bound, and MT-II 86%
      bound 6 h after the ligand had been removed from the assay medium. The relative
      dissociation rate of MT-II was 4 times slower than that for alpha-MSH and 2 times
      slower than that for MT-I, which was 2 times slower than that for alpha-MSH.
      These data suggest that slow dissociation kinetics (hours) may contribute to the
      prolonged biological activities observed for both MT-I and MT-II peptides in
      vitro and in vivo. The prolonged binding, biological activities, and enzymatic
      stability of MT-I and MT-II make them putative candidates for clinical uses such
      as external scintigraphy for the localization of tumors (i.e., melanoma).

PMID- 8558512
TI  - Studies on 6-aminoquinolones: synthesis and antibacterial evaluation of 6-amino-8
      methylquinolones.
AB  - The 6-aminoquinolone had previously been identified as a new class of quinolone
      antibacterial agents. To continue our structure-activity relationship (SAR) study
      in this series, novel 6-amino-8-methylquinolone derivatives have now been
      synthesized and evaluated for in vitro antibacterial activity. We have shown that
      the coupled presence of a methyl group at the C-8 position with an amino group at
      C-6 is effective for enhancing antibacterial activity, particularly against Gram
      positive bacteria. The SARs associated with the N-1, C-6, and C-7 are discussed.
      The 1,2,3,4-tetrahydroisoquinolinyl derivative 19v showed the highest
      antibacterial activity with MIC values on Gram-positive bacteria superior to that
      of ciprofloxacin, especially against Staphylococcus aureus strains, including
      those strains which are methicillin-and ciprofloxacin-resistant.

PMID- 8558513
TI  - The chemistry of Pseudomonic acid. 15. Synthesis and antibacterial activity of a
      series of 5-alkyl, 5-alkenyl, and 5-heterosubstituted oxazoles.
AB  - The synthesis of a range of 5-alkyl, 5-alkenyl, and 5-heterosubstituted 2-(1
      normon-2-yl) oxazoles is described. The antibacterial activity was determined as
      the minimum inhibitory concentration against a range of Gram-positive and Gram
      negative organisms using a standard Agar dilution procedure. Compounds possessing
      an acid functionality directly on, or close to, the ring were found to be of
      greatly decreased potency, while increasing lipophilicity with greater chain
      length led to increased potency of these derivatives.

PMID- 8558514
TI  - Indium (III) and gallium (III) complexes of bis(aminoethanethiol) ligands with
      different denticities: stabilities, molecular modeling, and in vivo behavior.
AB  - Complexes of Ga(III) and In(III) radionuclides are widely used in diagnostic
      imaging. In this study, the following ligands of denticities 4, 5, and 6
      respectively were prepared: N,N'-bis-(2,2-dimethyl-2-mercaptoethyl)
      ethylenediamine (4SS), 1-carboxy-N-N'-bis(2,2-dimethyl-2-
      mercaptoethyl)ethylenediamine (5SS), and N,N'-bis(2,2- dimethyl-2
      mercaptoethyl)ethylenediamine-N,N'-diacetic acid (6SS). Syntheses of the two new
      ligands, 5SS and 6SS, are described. Equilibrium constants for their In(III) and
      Ga(III) complexes were determined by both direct and ligand-competitive
      potentiometric methods. The formation constant (KML = [ML]/[M][L]) of In(III)-
      6SS in 0.100 M KNO3 at 25.0 degrees C is 10(39.8), and its pM at physiological pH
      (7.4 with 100% excess of the ligand) is 30.9. These values are higher than those
      of any other previous reported ligand for In(III). The stability constants of the
      complexes of 4SS, 5SS, 6SS, and the analogous ligand EDDASS, N,N'-bis(2
      mercaptoethyl) ethylenediamine-N,N'-diacetic acid, which does not contain gem
      dimethyl groups, are compared. The thermodynamic stabilities of the In(III)
      complexes of all ligands except 6SS are greater than those of the corresponding
      Ga(III) complexes. The presence of the geminal dimethyl groups in 6SS increased
      the stability of the Ga(III) and In(III) complexes over those of EDDASS. The
      effects of the gem-dimethyl groups on complex stabilities are explained by
      molecular modeling. The serum stabilities and biodistributions out to 1 h
      postinjection of 67/68Ga and 111In chelates of 4SS, 5SS, and 6SS were measured
      and compared with those of EDDASS. The 67/68Ga- and 111In-ligand complexes with
      more donor atoms showed were more stable in serum, both in vitro and in vivo. The
      biodistributions of the 67/68Ga- and 111In-ligand complexes exhibited distinct
      trends. None of the 67/68Ga- and 111In-chelates demonstrated significant heart or
      brain uptake. The majority of uptake for all compounds was in the liver and
      kidney. The degree of clearance through the liver corresponded to the
      thermodynamic stability of the complex. Correlations between in vivo behavior,
      molecular modeling data, and thermodynamic stability of the complexes are
      discussed.

PMID- 8558515
TI  - Structure-activity analysis of anandamide analogs: relationship to a cannabinoid
      pharmacophore.
AB  - Anandamides are endogenous fatty acid ethanolamides that have been shown to bind
      to the cannabinoid receptor and possess cannabimimetic activity yet are
      structurally dissimilar from the classical cannabinoids found in Cannabis sativa.
      We have employed molecular dynamics studies of a variety of anandamides to
      characterize their conformational mobility and determine whether there are
      pharmacophoric similarities with delta 9-THC. We have found that a looped
      conformation of these arachidonyl compounds is energetically favorable and that a
      structural correlation between this low-energy conformation and the classical
      cannabinoids can be obtained with the superposition of (1) the oxygen of the
      carboxyamide with the pyran oxygen in delta 9-THC, (2) the hydroxyl group of the
      ethanol with the phenolic hydroxyl group of delta 9-THC, (3) the five terminal
      carbons and the pentyl side chain of delta9-THC, and (4) the polyolefin loop
      overlaying with the cannabinoid tricyclic ring. The shape similarity is extended
      to show that other fatty acid ethanolamides that possess varying degrees of
      unsaturation also vary in their conformational mobility, which affects their
      ability to overlay with delta 9-THC as described above. Within this series of
      compounds, the most potent analog, the tetraene (arachidonyl) analog (i.e.,
      anandamide itself), was determined to have restricted conformational mobility
      that favored an optimal pharmacophore overlay with delta9-THC. Eight
      pharmacologically active anandamide analogs are shown to have similar
      conformational mobility and pharmacophore alignments that are conformationally
      accessible. Furthermore, when these compounds are aligned to delta 9-THC
      according to the proposed pharmacophore overlay, their potencies are predicted by
      a quantitative model of cannabinoid structure--activity relationships based
      solely on classical and nonclassical cannabinoids with a reasonable degree of
      accuracy. The ability to incorporate the pharmacological potency of these
      anandamides into the cannabinoid pharmacophore model is also shown to support the
      relevance of the proposed pharmacophore model.

PMID- 8558516
TI  - Investigation of (Oxodioxolenyl)methyl carbamates as nonchiral bioreversible
      prodrug moieties for chiral amines.
AB  - The preparation of (oxodioxolenyl)methyl carbamates and their evaluation as novel
      nonchiral prodrug moieties for chiral primary and secondary amino functional
      drugs are described. 4-(Carbamoylmethyl)-2-oxo-1,3-dioxolene derivatives of 3,4
      dimethoxyphenethylamine with 5-methyl, 5-phenyl, and 5-anisyl substitution (5a,
      5b, and 5c) on the dioxolenone ring were prepared as model amine prodrugs by a
      one step process involving displacement of p-nitrophenol from appropriately
      substituted ring opening of these carbamates led to a cascade reaction resulting
      in the rapid and quantitative regeneration of the parent amine drug. Aryl
      substitution did not significantly alter the hydrolysis rates of these
      dioxolenone carbamates in buffers at pH 1 and 7.4 or in rat plasma, although the
      hydrolysis rates of 5-phenyl- (1b) and 5-anisyl- 4-methyl-1,3-dioxol-4-en-2-one
      (1c) in pH 7.4 phosphate buffer were 2-3 fold faster than that of the 5-methyl
      substituted analog (1a). Application of this prodrug strategy to the chiral
      fibrinogen receptor antagonist L-734,217 resulted in a prodrug that gave
      quantitative reconversion in rat and dog plasma in vitro and oral bioavailability
      of 23 +/- 6% in dogs for the parent drug.

PMID- 8558517
TI  - Design, synthesis, and structure-activity relationship studies of novel 1-[(1
      acyl-4-piperidyl)methyl]-1H-2- methylimidazo[4,5-c]pyridine derivatives as
      potent, orally active platelet-activating factor antagonists.
AB  - Replacement of the polar head of our previous series of 1-acyl-4-[(2-methyl-3
      pyridyl)-cyanomethyl]piperazines with a 2-methylimidazo[4,5-c]pyridine group has
      led to the identification of a new series of 1-[(1-acyl-4- piperidyl)methyl]-1H-2
      methylimidazo[4,5-c]pyridine derivatives as potent, orally active platelet
      activating factor (PAF) antagonists. On the basis of the general structure-
      activity relationship trends found for the acyl substituent in our earlier
      series, five groups of compounds were tested, diaryl- or alkylarylpropanoyl
      derivatives, their 3-hydroxy-substituted analogues, and urea, carbamate and amino
      acid derivatives. The optimal compound 19 UR-12670), bearing the 3,3
      diphenylpropanoyl moiety, exhibited very high in vitro and in vivo potency IC50 =
      0.0076 microM for the in vitro PAF-induced platelet aggregation assay, ID50 =
      0.0086 mg/kg for the in vivo PAF-induced hypotension test in normotensive rats,
      and ID50 = 0.092 mg/kg po and 0.0008 mg/kg i.v. for the PAF-induced mortality
      test in mice). Compound 19 also showed long duration of activity. It gave 100%
      protection against PAF-induced mortality in mice 7 h after i.v. administration of
      a single dose of 1 mg/kg and also provided 100% inhibition of PAF-induced
      aggregation in dog whole blood 6 h after i.v. administration of the same dose.
      The lead structure 19 has been selected for in-depth pharmacological evaluation.

PMID- 8558518
TI  - Dual metalloprotease inhibitors. 6. Incorporation of bicyclic and substituted
      monocyclic azepinones as dipeptide surrogates in angiotensin-converting
      enzyme/neutral endopeptidase inhibitors.
AB  - A series of substituted monocyclic and bicyclic azepinones were incorporated as
      dipeptide surrogates in mercaptoacetyl dipeptides with the desire to generate a
      single compound which would potently inhibit both angiotensin-converting enzyme
      (ACE) and neutral endopeptidase (NEP). Many of these compounds displayed
      excellent potency against both enzymes. Two of the most potent compounds,
      monocyclic azepinone 2n and bicyclic azepinone 3q, demonstrated a high level of
      activity versus ACE and NEP both in vitro and in vivo.

PMID- 8558519
TI  - Metal-chelating inhibitors of a zinc finger protein HIV-EP1. Remarkable
      potentiation of inhibitory activity by introduction of SH groups.
AB  - HIV-EP1 is a C2H2 type zinc finger protein which binds to DNA kappa B site
      present in the long terminal repeat of HIV provirus. Previously we have reported
      zinc chelators having histidine--pyridine--histidine skeleton and were successful
      in inhibiting the DNA binding of HIV-EP1 by removing zinc from the zinc finger
      domain. Aiming at the potentiation of the inhibitory activity of our previous
      zinc chelators, herein synthesized were novel chelators comprising pyridine and
      aminoalkanethiol. These showed marked inhibitory activity on the DNA binding of
      HIV-EP1. In particular, one of them having a bis(2-mercaptoethyl) amino side
      chain showed inhibitory activity (IC50, approximately 4 microM) 10 times stronger
      than that of the strongest inhibitor that we reported previously. It appeared
      that these inhibited the DNA binding of HIV-EP1 by a mechanism distinct from that
      of the previous histidine-based inhibitors.

PMID- 8558520
TI  - Correlation of anti-HIV potency with lipophilicity in a series of cosalane
      analogs having normal alkenyl and phosphodiester chains as cholestane
      replacements.
AB  - In order to define the role of the cholestane moiety in the anti-HIV agent
      cosalane, a series of cosalane analogs was synthesized in which the cholestane
      ring system was replaced by normal alkenyl and phosphodiester substituents having
      varied chain lengths and lipophilicities. The compounds containing simple alkenyl
      substituents were found to be more potent as inhibitors of the cytopathic effect
      of HIV-1 in cell culture than the phosphodiesters. In addition, the potencies of
      the alkene congeners correlated positively with chain length and lipophilicity of
      the alkene. The results indicate that the cholestane moiety of cosalane functions
      as a lipophilic accessory appendage to escort the dichlorodisalicylmethane
      pharmacophore to a lipid environment.

PMID- 8558521
TI  - Neuroactive polyamine wasp toxins: nuclear magnetic resonance spectroscopic
      analysis of the protolytic properties of philanthotoxin-343.
AB  - Acid-base properties (pKa values and proton distribution patterns) of
      philanthotoxin-343(PhTX-343) were investigated by 1H and 13C NMR titration.
      Chemical shift data and the total ionization shifts were used to assign carbon
      atoms of the polyamine chain. Nonlinear analysis of the 13C NMR titration curves
      gave four pKa values (pK1 8.5, pK2 9.5, pK3 10.4, pK4 11.4) and the intrinsic
      chemical shifts of the non-, mono-, di-, tri-, and tetraprotonated forms. The
      changes of intrinsic chemical shifts enabled analysis of the deprotonation
      sequence of fully protonated PhTX-343. The results of analysis of the 13C NMR
      titration curves were supported by 1H NMR data obtained from two-dimensional 1H,
      13C chemical shift correlation experiments. Thus, the first deprotonation mainly
      takes place at the inner amino group. The phenol group is deprotonated in the
      second and third deprotonation steps. The preferential deprotonation of the inner
      amino group is also apparent in the deprotonated form. The monoprotonated form
      carries a practically fully ionized phenol group and the proton shared between
      the three amino groups. This characteristic is in agreement with existing data on
      polyamines. At physiological pH, the tetraprotonated form of PhTX-343
      predominates, but the proportion of the triprotonated form becomes significant at
      low ionic strength. The terminal, primary amino group, which has been shown to be
      essential for biological activity, remains practically fully protonated at
      biologically relevant pH values, and this charge is likely to participate in the
      receptor-binding event. Protonation of the central amino group does not appear to
      be necessary for biological activity.

PMID- 8558522
TI  - 2-Sulfonyl-4-chloroanilino moiety: a potent pharmacophore for the anti-human
      immunodeficiency virus type 1 activity of pyrrolyl aryl sulfones.
AB  - The synthesis and the evaluation of cytotoxicity and anti-HIV-1 activity of new
      aryl pyrrolyl (8) and aryl indolyl (9) sulfones are reported. Preparation of
      above sulfones was achieved by reacting arylsulfonyl chlorides with substituted
      pyrroles and indoles or by condensing sulfonamides with 2,5
      dimethoxytetrahydrofuran in glacial acetic acid according to the Clauson-Kaas
      method. Chemical requisites relevant to the anti-HIV-1 activity of these
      compounds are both a 2-sulfonyl-4-chloroanilino moiety and an alkoxycarbonyl
      group at position 2 of the pyrrole ring. The best activity and selectivity were
      obtained with ethoxycarbonyl and isopropoxycarbonyl substituents. Substitutions
      at the amino group of the pharmacophore moiety led to inactive products
      (alkylation) or weakened (acylation) anti-HIV-1 activity. Among test derivatives,
      16 compounds showed EC50 values ranging between 10 and 1 microM, and five
      (8b',d',f',h'j') showed EC50S in the sub-micromolar range. The compounds were
      active against HIV-1, both wild type and AZT-resistant strains, but not against
      HIV-2. Moreover, in enzyme assays they potently inhibited the HIV-1 recombinant
      reverse transcriptase, were 10 times less active against enzymes from nevirapine-
      and TIBO-resistant strains, and were totally inactive against the HIV-2
      recombinant enzyme. Interestingly, some compounds (8r'-y') were inactive against
      the recombinant reverse transcriptase while being active in tissue culture.

PMID- 8558523
TI  - Cross-linking and sequence specific alkylation of DNA BY aziridinylquinones. 1.
      Quinone methides.
AB  - The cytotoxicities and DNA cross-linking abilities of 16 1,4-benzoquinones have
      been investigated. All of the alkylmonoaziridinyl-1,4-benzoquinones were able to
      interstrand crosslink DNA after reduction and were cytotoxic in vitro. Compounds
      lacking an aziridine group were unable to cross-link DNA and were less cytotoxic.
      The methyl analogues were shown to preferentially react at TGC sequences. From
      comparing the structural requirements for crosslinking and the cytotoxicities, a
      mechanism has been proposed wherein some hydroquinones can associate and react at
      TGC sequences in DNA. These hydroquinones can subsequently autoxidize to form a
      reactive quinone methide which reacts at the opposite strand to form a cross
      link.

PMID- 8558524
TI  - Synthesis and antiviral activity of 2'-deoxy-4'-thio purine nucleosides.
AB  - A series of 2'-deoxy-4'-thioribo purine nucleosides was prepared by trans-N
      deoxyribosylase-catalyzed reaction of 2'-deoxy-4'-thiouridine with a variety of
      purine bases. This synthetic procedure is an improvement over methods previously
      used to prepare purine 4'-thio nucleosides. The compounds were tested against
      hepatitis B virus (HBV), human cytomegalovirus (HCMV), herpes simplex virus (HSV
      1 and HSV-2), varicella zoster virus (VZV), and human immunodeficiency virus (HIV
      1). Cytotoxicity was determined in a number of cell lines. Several compounds were
      extremely potent against HBV and HCMV and had moderate to severe cytotoxicity in
      vitro. The lead compound from the series, 2-amino-6-(cyclopropylamino)purine 2'
      deoxy-4'-thioriboside, was the most potent and selective agent against HCMV and
      HBV replication in vitro; however, this analogue was nephrotoxic when tested in
      vivo.

PMID- 8558525
TI  - N-substituted analogs of 2 beta-carbomethoxy-3 beta- (4'-iodophenyl)tropane (beta
      CIT) with selective affinity to dopamine or serotonin transporters in rat
      forebrain.
AB  - This report concerns the synthesis and chemical characterization of novel series
      of N-substituted 2 beta-carbomethoxy-3 beta-(4'-iodophenyl)tropane (beta-CIT, 2)
      analogs and their neuropharmacological evaluation for affinity at dopamine (DAT),
      serotonin (5-HTT), and norepinephrine membrane transporters in rat brain tissue.
      N-Substituted analogs of beta-CIT with a 2 beta-carbomethoxy ester moiety showed
      lower DAT affinity than beta-CIT for the DAT, and some were more selective for
      the 5-HTT over the DAT. 2 beta-Carbomethoxy(iodophenyl)nortropane analogs of beta
      CIT with the N-substituents difluoroethyl, mesoxypropyl, iodopropyl, and
      methylpropionyl all yielded > 10-fold lower DAT affinity than beta-CIT itself,
      whereas the N-(fluoropropyl)-2 beta- isopropyl ester analog (1) of beta-CIT
      exceeded beta-CIT (2, an N-methyl-2 beta-carbomethoxy ester) in DAT affinity.
      Several N-haloalkyl-substituted beta-CIT analogs yielded high 5-HTT affinity (Ki
      < 0.6 nM), ranking: N-fluoropropyl (5) > N-chloropropyl (4) > or = N-bromopropyl
      (3) > beta-CIT (2) > N-3'-phtalimidopropyl (11), with particularly high (ca. 30
      fold) 5-HTT-over-DAT selectivity found in the N-fluoropropyl (5) and N
      fluoroethyl (6) compounds, compared to only 3.o-fold 5-HTT selectivity in beta
      CIT itself. Highly 5-HTT selective agents such as 5 and 6 may be useful as brain
      imaging ligands for serotonin neurons or as mood-elevating drugs, while the high
      affinity and selectivity for the DA transporter found in N-(fluoropropyl)-2 beta
      (carboxyisopropyl)-3 beta-(4'-iodophenyl)-nortropane (1) and N-(fluoropropyl)-2
      beta-carboxymethoxy-3 bet-(4'-iodophenyl)nortropane (FP-beta-CIT, 5) support
      their use as improved markers for DA neurons.

PMID- 8558526
TI  - 9-Dihydroxy-2,3,7,11b-tetrahydro-1H-naph[1,2,3-de]isoquinoline: a potent full
      dopamine D1 agonist containing a rigid-beta-phenyldopamine pharmacophore.
AB  - The present work reports the synthesis and preliminary pharmacological
      characterization of 8,9-dihydroxy-2,3,7,11b-tetrahydro-1H-naph[1,2,3-de]
      isoquinoline (4, dinapsoline). This molecule was designed to conserve the
      essential elements contained in our D1 agonist pharmacophore model (i.e.,
      position and orientation of the nitrogen, hydroxyls, and phenyl rings). It
      involved taking the backbone of dihydrexidine [3; (+/-)-trans-10, 11-dihydroxy
      5,6,6a,7,8,12b-hexahydrobenzo[a] phenanthridine], the first high-affinity full D1
      agonist, and tethering the two phenyl rings of dihydrexidine through a methylene
      bridge and removing the C(7)-C(8) ethano bridge. Preliminary molecular modeling
      studies demonstrated that these modifications conserved the essential elements of
      the hypothesized pharmacopore. Dinapsoline 4 had almost identical affinity (KI =
      5.9 nM) to 3 at rat striatal D1 receptors and had a shallow competition curve (nH
      = 0.66) that suggested agonist properties. Consistent with this, in both rat
      striatum and C-6-mD1 cells, dinapsoline 4 was a full agonist with an EC50 of ca.
      30 nM in stimulating synthesis of cAMP via D1 receptors. The design and synthesis
      of dinapsoline 4 provide a powerful test of the model of the D1 pharmacophore we
      have developed and provide another chemical series that can be useful probes for
      the study of D1 receptors. An interesting property of 3 is that it also has
      relatively high D2 affinity (K0.5 = 50 nM) despite having an accessory phenyl
      ring usually though to convey D1 selectivity. Dinapsoline 4 was found to have
      even higher affinity for the D2 receptor (K0.5 = 31 nM) than 3. Because of the
      high affinity of 4 for D2 receptors, it and its analogs can be powerful tools for
      exploring the mechanisms of "functional selectivity" (i.e., that 3 is an agonist
      at some D2 receptors, but an antagonist at others). Together, these data suggest
      that 4 and its derivatives may be powerful tools in the study of dopamine
      receptor function and also have potential clinical utility in Parkinson's disease
      and other conditions where perturbation of dopamine receptors is useful.

PMID- 8558527
TI  - Approaches to short-acting neuromuscular blocking agents: nonsymmetrical bis
      tetrahydroisoquinolinium mono- and diesters.
AB  - Nonsymmetrical bisquaternary mono- and diesters combining the potency-enhancing
      properties of the (1R)-laudanosinium group with a second unhindered quaternary
      ammonium moiety have been studied as a means of promoting short action with high
      potency neuromuscular block. Atracurium-related nonsymmetrical diesters showed
      high potency, freedom from vagal blockade at neuromuscular blocking doses, and
      short action. Nonsymmetrical monoesters were short acting but showed varying
      degrees of vagal block.

PMID- 8558528
TI  - Discovery of 1,5-benzodiazepines with peripheral cholecystokinin (CCK-A) receptor
      agonist activity. 1. Optimization of the agonist "trigger".
AB  - Directed screening of compounds selected from the Glaxo registry file for
      contractile activity on the isolated guinea pig gallbladder (GPGB) identified a
      series of 1,5-benzodiazepines with peripheral cholecystokinin (CCK) receptor
      agonist activity. Agonist efficacy within this series was modulated by variation
      of substituents on the N1-anilinoacetamide moiety. Remarkably, a single methyl
      group confers agonist activity, with an N-isopropyl substituent providing optimal
      efficacy. Hydrophilic substituents on the anilino nitrogen abolish agonist
      activity or produce antagonists of CCK. In contrast, hydrophilic electron
      donating groups at the para-position of the anilino ring enhance or maintain in
      vitro and in vivo agonist activity. Despite decreased affinity for the human CCK
      A receptor, relative to CCK-8, some of these compounds are equipotent to CCK as
      anorectic agents in rats following intraperitoneal administration.

PMID- 8558529
TI  - Synthesis and structure-activity relationships of N-propyl-N-(4-pyridinyl)-1H
      indol-1-amine (besipirdine) and related analogs as potential therapeutic agents
      for Alzheimer's disease.
AB  - A series of novel N-(4-pyridinyl)-1H-indol-1-amines and other heteroaryl analogs
      was synthesized and evaluated in tests to determine potential utility for the
      treatment of Alzheimer's disease. From these compounds, N-propyl-N-(4-pyridinyl)
      1H-indol-1-amine (besipirdine, 4c) was selected for clinical development based on
      in-depth biological evaluation. In addition to cholinomimetic properties based
      initially on in vitro inhibition of [3H]quinuclidinyl benzilate binding, in vivo
      reversal of scopolamine-induced behavioral deficits, and subsequently on other
      results, 4c also displayed enhancement of adrenergic mechanisms as evidenced in
      vitro by inhibition of [3H] clonidine binding and synaptosomal biogenic amine
      uptake, and in vivo by reversal of tetrabenazine-induced ptosis. The synthesis,
      structure-activity relationships for this series, and the biological profile of
      4c are reported.

PMID- 8558530
TI  - Substituted (pyrroloamino)pyridines: potential agents for the treatment of
      Alzheimer's disease.
AB  - A novel series of substituted (pyrroloamino)pyridines was synthesized, and the
      compounds were evaluated for cholinomimetic-like properties in vitro (inhibition
      of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine
      induced dementia) as potential agents for the treatment of Alzheimer's disease.
      Compounds displaying significant activity were more broadly evaluated, which
      revealed the presence of a desirable adrenergic component of activity. The
      synthesis and structure-activity relationships for this series is presented,
      along with the biological profiles of selected compounds.

PMID- 8558531
TI  - Ionophore properties of monensin derivatives studied on human erythrocytes by
      23Na NMR and K+ and H+ potentiometry: relationship with antimicrobial and
      antimalarial activities.
AB  - Eight derivatives of monensin with a modified C25-C26 moiety were synthesized.
      Their ionophore properties were studied on human erythrocytes by measuring Na+
      influx with 23Na NMR and concomitant K+ and H+ efflux by potentiometry.
      Modification of OH-26 led to inversion of selectivity of transport in favor of
      K+/Na+ in comparison with monensin. This selectivity disappeared by suppression
      of the C26-OH moiety. Finally the ionophore ability was lost if the head-to-tail
      chelation of the monensin skeleton was prevented by blocking the terminal OH-25
      and -26 functions. All the compounds were inactive on Gram-negative bacteria and
      fungi. MIC measured on Bacillus cereus showed that derivatives with increased
      K+/Na+ selectivity were clearly the most active against Bacillus growth. Most of
      the compounds showed potential antimalarial properties in the nanomolar range
      when tested in vitro against Plasmodium falciparum. The IC50S measured were
      correlated with the whole Na+ and K+ transport efficiency rather than with the
      ionic selectivity. In both cases determination of initial fluxes of transport for
      both cations (Na+ and K+) was necessary to investigate the relationship between
      biological and ionophore properties.

PMID- 8558532
TI  - 2-[(2-Aminobenzyl)sulfinyl]-1-(2-pyridyl)-1,4,5,6
      tetrahydrocyclopent[d]imidazoles as a novel class of gastric H+/K+-ATPase
      inhibitors.
AB  - Substituted 2-sulfinylimidazoles were synthesized and investigated as potential
      inhibitors of gastric H+/K(+)-ATPase. The 4,5-unsubstituted imidazole series 6-11
      and the 1,4,5,6-tetrahydrocyclopent[d]imidazole series 12 were found to be potent
      inhibitors of the acid secretory enzyme H+/K(+)-ATPase. Structure-activity
      relationships indicate that the substitution of 2-pyridyl groups at the 1
      position of the imidazole moiety combined with (2-aminobenzyl)-sulfinyl groups at
      the 2-position leads to highly active compounds with a favorable chemical
      stability. Other substitution patterns in the imidazole moiety result in reducing
      biological activities. 2-[(2-Aminobenzyl) sulfinyl]-1-[2-(3-methylpyridyl)]
      1,4,5,6-tetrahydrocyclopent++ ++ ++ [d]-imidazole (12h, T-776) was selected for
      further development as a potential clinical candidate. Extensive study on the
      acid degradation of 12h indicates a mechanism of action different from that of
      omeprazole, the first H+/K(+)-ATPase inhibitor introduced to the market.

PMID- 8558533
TI  - Antitumor activity of the R- and S-enantiomers of RS-2-[[hydroxy[[2-[
      (octadecyloxy)methyl]tetrahydrofuran-2-yl]methoxy]-phosphinyl]oxy]-N, N,N,
      trimethylethylaminium hydroxide inner salt.
AB  - The R- and S-enantiomers of 2-[[hydroxyl[[2-[(octadecyloxy)
      methyl]tetrahydrofuran-2-yl]methoxy]-phosphinyl]oxy]-N,N,N,-
      trimethylethylaminium hydroxide salt (SRI 62-834) have been evaluated in several
      assays to determine potential antitumor activity. The S-enantiomer showed
      slightly greater cytotoxic activity than the R- or RS-forms against several
      murine tumor cell lines. In the mouse Meth A fibrosarcoma model, the S-enantiomer
      was ca. 4 times more effective than the R-isomer in controlling size of tumor
      growth and increasing the number of survivors.

PMID- 8558534
TI  - Aminoacetyl moiety as a potential surrogate for diacylhydrazine group of SC
      51089, a potent PGE2 antagonist, and its analogs.
AB  - 8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4
      pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a functional PGE2
      antagonist selective for the EP1 receptor subtype with antinociceptive activity.
      During metabolism in cultured rat hepatocytes, SC-51089, which contains a
      diacylhydrazine moiety, has been shown to release hydrazine. Analogs of SC-51089,
      in which the diacylhydrazine functionality has been replaced by isosteric and
      isoelectronic groups, have been synthesized and have been shown to be analgesics
      and PGE2 antagonists of the EP1 subtype. This report discusses the structure
      activity relationships within these series.

PMID- 8558535
TI  - Analogues of 10-deazaaminopterin and 5-alkyl-5,10-dideazaaminopterin with the 4
      substituted 1-naphthoyl group in the place of 4-substituted benzoyl.
AB  - 10-Deaza modifications of classical antifolate analogues bearing the 1,4
      disubstituted naphthalene ring in place of the 1,4-disubstituted benzene ring
      were prepared and tested for antitumor activity. Naphthalene analogues (9a-c,
      respectively) of 10-deazaaminopterin, 5-methyl-5, 10-dideazaaminopterin, and 5
      ethyl-5,10-dideazaaminopterin were prepared by a route consisting of C
      alkylations of the anion derived from 4-carboxyl-1-naphthaleneacetic acid
      dimethyl ester (2) by 6-(bromomethyl)-2,4-diaminopteridine (1a) and 6
      (bromomethyl)-2,4-diamino-5-methyl- and -5-deazapteridines (1b and 1c,
      respectively) followed by ester hydrolysis and subsequent decarboxylation to give
      naphthalene analogues (7a-c, respectively) of 4-amino-4-deoxy-10-deazapteroic
      acid and 4-amino-4-deoxy-5- methyl- and -5-ethyl-5,10-dideazapteroic acids.
      Peptide coupling of 7a-c with L-glutamic acid dialkyl ester followed by mild
      ester hydrolysis gave target compounds 9a-c. The key advantage of this route is
      circumvention of a hydrogenation step requiring selectivity as in earlier
      approaches involving 9,10-olefinic precursors. Steric limitations thwarted plans
      to prepare the naphthalene analogue of 10-ethyl-10-deazaaminopterin; attempted
      alkylations of 2-(4-carboxy-1-naphthyl)butyric acid dimethyl ester with 1a failed
      as did attempted further alkylation (by EtBr) of the product derived from 1a and
      2. Growth inhibition tests against three tumor cell lines (L1210, S180, and HL60)
      showed 9a to be 4-6-fold more inhibitory than methotrexate but not as inhibitory
      as 10-ethyl-10-deazaaminopterin; 9b and 9c were no more inhibitory than MTX. In
      tests against the EO771 mammary adenocarcinoma in mice, 9a was less active than
      MTX.

PMID- 8558536
TI  - Design, synthesis, and biological activity of a potent inhibitor of the
      neuropeptidase N-acetylated alpha-linked acidic dipeptidase.
AB  - A series of substituted phosphonate derivatives were designed and synthesized in
      order to study the ability of these compounds to inhibit the neuropeptidase N
      acetylated alpha-linked acidic dipeptidase (NAALADase). The molecules were shown
      to act as inhibitors of the enzyme, with the most potent (compound 3) having a Ki
      of 0.275 nM. The potency of this compound is more than 1000 times greater than
      that of previously reported inhibitors of the enzyme. NAALADase is responsible
      for the catabolism of the abundant neuropeptide N-acetyl-aspartylglutamate (NAAG)
      into N-acetylaspartate and glutamate. NAAG has been proposed to be a
      neurotransmitter at a subpopulation of glutamate receptors; alternatively, NAAG
      has been suggested to act as a storage form of synaptic glutamate. As a result,
      inhibition of NAALADase may show utility as a therapeutic intervention in
      diseases in which altered levels of glutamate are thought to be involved.

PMID- 8558537
TI  - Evidence based medicine and ethics.

PMID- 8558538
TI  - Procuring gametes for research and therapy.

PMID- 8558539
TI  - Killing, karma and caring: euthanasia in Buddhism and Christianity.
AB  - In 1993 The Parliament of the World's Religions produced a declaration known as A
      Global Ethic which set out fundamental points of agreement on moral tissues
      between the religions of the world. However, the declaration did not deal
      explicitly with medical ethics. This article examines Buddhist and Christian
      perspectives on euthanasia and finds that in spite of their cultural and
      theological differences both oppose it for broadly similar reasons. Both
      traditions reject consequentialist patterns of justification and espouse a
      'sanctity of life' position which precludes the intentional destruction of human
      life by act or omission.

PMID- 8558540
TI  - Differences between death and dying.
AB  - With so much attention being paid to the development and refinement of
      appropriate criteria and tests for death, little attention has been given to the
      broader conceptual issues having to do with its definition or with the relation
      of a definition to its criterion. The task of selecting the correct criterion is,
      however, virtually impossible without proper attention to the broader conceptual
      setting in which the definition operates as the key feature. All of the issues I
      will discuss arise because of this lack of concern with conceptual matters. Such
      problems as incorrectly diagnosing a patient as dead prior to the harvesting of
      his or her organs, defending the idea that death is reversible, and advocating a
      brainstem criterion of death, are all, I believe, errors that derive from this
      misplaced emphasis.

PMID- 8558541
TI  - The ultimate curse.
AB  - This paper tells the story of a doctor in a vegetative state. The approach
      towards him is quite different from that towards a common patient. The other
      physicians cannot deal with this situation with the necessary open mind.

PMID- 8558542
TI  - Smokers' rights to health care.
AB  - The question whether rights to health care should be altered by smoking behaviour
      involves wideranging implications for all who indulge in hazardous behaviours,
      and involves complex economic utilitarian arguments. This paper examines current
      debate in the UK and suggest the major significance of the controversy has been
      ignored. That this discussion exists at all implies increasing division over the
      scope and purpose of a nationalised health service, bestowing health rights on
      all. When individuals bear the cost of their own health care, they appear to take
      responsibility for health implications of personal behaviour, but when the state
      bears the cost, moral obligations of the community and its doctors to care for
      those who do not value health are called into question. The debate has far
      reaching implications as ethical problems of smokers' rights to health care are
      common to situations where health as a value comes into conflict with other
      values, such as pleasure or wealth.

PMID- 8558543
TI  - Why bioethicists have nothing useful to say about health care rationing.
AB  - Bioethicists are increasingly commenting on health care resource allocation, and
      sometimes suggest ways to solve various rationing dilemmas ethically. I argue
      that both because of the assumptions bioethicists make about social reality, and
      because of the methods of argument they use, they cannot possibly make a useful
      contribution to the debate. Bioethicists who want to make a practical difference
      should either approach health care resource allocation as if the matter hinged
      upon tribal competition (which is essentially what it does), or they should do
      political philosophy in the traditional sense, and examine the health system from
      the outside.

PMID- 8558544
TI  - Prenatal diagnosis: whose right?
AB  - The question who is the subject of the right to prenatal diagnosis may be
      answered in four ways: the parents, the child, society, or no one. This article
      investigates the philosophical issues involved in each of these answers, which
      touch upon the conditions of personal identity, the principle of privacy, the
      scope of social responsibility, and the debate about impersonalism in ethics.

PMID- 8558545
TI  - Mummy was a fetus: motherhood and fetal ovarian transplantation.
AB  - Infertility affects 15 per cent of the world's couples. Research at Edinburgh
      University has been directed at transplanting fetal ovarian tissue into infertile
      women, thus enabling them to bear children. Fetal ovary transplantation (FOT) has
      generated substantial controversy; in fact, one ethicist deemed the procedure 'so
      grotesque as to be unbelievable' (1). Some have suggested that fetal eggs may
      harbour unknown chromosomal abnormalities: however, there is no evidence that
      these eggs possess a higher incidence of genetic anomaly than ova found in a
      healthy adult female. There is also concern that fetal egg children will be
      psychologically harmed by the knowledge of their special conceptual status. It
      will be demonstrated that special conceptual status in and of itself does not
      determine developmental success. Rather, psychological well-being is dependent
      upon how the family and child cope with the unique challenges inherent in FOT.
      Lastly, though considering FOT a legitimate method of family building, given the
      global population crisis the wisdom of procreational rights will be challenged.
      Inherent to this challenge is a re-evaluation of the treatment of infertility as
      a significant disease necessitating remedy.

PMID- 8558546
TI  - Autonomy, problem-based learning, and the teaching of medical ethics.
AB  - Autonomy has been the central principle underpinning changes which have affected
      the practice of medicine in recent years. Medical education is undergoing changes
      as well, many of which are underpinned, at least implicitly, by increasing
      concern for autonomy. Some universities have embarked on graduate courses which
      utilize problem-based learning (PBL) techniques to teach all areas, including
      medical ethics. I argue that PBL is a desirable method for teaching and learning
      in medical ethics. It is desirable because the nature of ethical enquiry is
      highly compatible with the learning processes which characterize PBL. But it is
      also desirable because it should help keep open the question of what autonomy
      really is, and how it should operate within the sphere of medical practice and
      medical education.

PMID- 8558547
TI  - No distinction between male and female circumcision.

PMID- 8558548
TI  - An ethical approach to HIV carriage and AIDS.

PMID- 8558549
TI  - Rhetorical devices are of no avail: a rejoinder to Peter Singer.

PMID- 8558550
TI  - FMR1 triplet arrays: paying the price for perfection.

PMID- 8558551
TI  - General overgrowth in the fragile X syndrome: variability in the phenotypic
      expression of the FMR1 gene mutation.

PMID- 8558552
TI  - Exclusion mapping of chromosomal regions which cross hybridise to FSHD1A
      associated markers in FSHD1B.

PMID- 8558553
TI  - Linkage analysis in blepharophimosis-ptosis syndrome confirms localisation to
      3q21-24.

PMID- 8558554
TI  - Bilateral cataract and high serum ferritin: a new dominant genetic disorder?

PMID- 8558555
TI  - Current issues of personnel and laboratory practices in genetic testing.

PMID- 8558556
TI  - Metachromatic leucodystrophy (MLD) in a patient with a constitutional ring
      chromosome 22.

PMID- 8558557
TI  - Familial partial trisomy 8p without dysmorphic features and only mild mental
      retardation.

PMID- 8558558
TI  - Public attitudes towards the selection of desirable characteristics in children.

PMID- 8558559
TI  - Adolescents' opinions about genetic risk information, prenatal diagnosis, and
      pregnancy termination.

PMID- 8558560
TI  - Treacher Collins syndrome.

PMID- 8558561
TI  - A new autosomal recessive syndrome of characteristic facies, joint contractures,
      skeletal abnormalities, and normal development: second report with further
      clinical delineation.

PMID- 8558562
TI  - An unusual pedigree with microcornea-cataract syndrome.

PMID- 8558563
TI  - Otofaciocervical syndrome: a sporadic patient supports splitting from the
      branchio-oto-renal syndrome.

PMID- 8558565
TI  - WAGR syndrome and multiple exostoses in a patient with del(11)(p11.2p14.2).

PMID- 8558564
TI  - Identification of an unbalanced cryptic translocation t(9;17)(q34.3;p13.3) in a
      child with dysmorphic features.

PMID- 8558566
TI  - Duplication 2 (q11.2-q21): a previously unreported abnormality.

PMID- 8558567
TI  - Characterisation of the unstable expanded CAG repeat in the MJD1 gene in four
      Brazilian families of Portuguese descent with Machado-Joseph disease.

PMID- 8558568
TI  - Short stature in a girl with partial monosomy of the pseudoautosomal region
      distal to DXYS15: further evidence for the assignment of the critical region for
      a pseudoautosomal growth gene(s).

PMID- 8558569
TI  - Reply to the commentary on Decruyenaere et al "adolescents' opinions about
      genetic risk information, prenatal diagnosis, and pregnancy termination".

PMID- 8558570
TI  - Glycogen storage disease type II: frequency of three common mutant alleles and
      their associated clinical phenotypes studied in 121 patients.

PMID- 8558571
TI  - Partial trisomy 3q and the mild Cornelia de Lange syndrome phenotype.

PMID- 8558572
TI  - Response to GIG's response to the UK Clinical Genetics Society report "the
      genetic testing of children".

PMID- 8558573
TI  - Allergic rhinitis.

PMID- 8558574
TI  - The diagnosis of sinusitis.
AB  - The diagnosis of sinusitis is usually based on evidence obtained from history
      taking and physical examination. The making of the diagnosis has been made easier
      recently by CT scanning and by the availability of the rigid Hopkins endoscopes.
      However, the diagnosis remains basically a clinical one. Radiologic and
      bacteriologic evidence may also help, but should be considered neither necessary
      nor required. Minor radiologic abnormalities are not infrequently seen in normal
      asymptomatic people and require no medical or surgical attention. Fungal
      sinusitis is on the increase. Sinusitis in children is briefly reviewed.

PMID- 8558575
TI  - Medical treatment of sinusitis.
AB  - Sinusitis is a very common and increasingly recognized disorder affecting
      patients of all ages and genders. It is most commonly due to infection of the
      paranasal sinuses with symptoms varying from cough and anterior nasal drainage in
      children to headache and post nasal drip in adults. Diagnosis relies heavily on
      medical history with corroboration by careful physical examination including
      nasal endoscopy. The most accurate imaging technique to evaluate sinusitis and to
      delineate the extent of involvement of individual sinuses and identify possible
      anatomic abnormalities is computerized tomography scanning in the coronal plane.
      The mainstay of medical treatment of sinusitis is antibiotics with adjuvant
      treatments such as saline irrigation, decongestants, mucolytics and
      antiinflammatory agents playing a more secondary role. The use of these agents
      will be discussed in detail after an introduction about the risk factors,
      diagnosis and bacteriology of the disease. Surgical treatment of sinusitis will
      be the subject of another article.

PMID- 8558576
TI  - Surgical treatment of sinusitis.
AB  - Chronic sinusitis has become more widely recognized recently because of the
      improved diagnostic tools that are now available. The advent of the nasal
      endoscopes and computed tomography scans have revolutionized our understanding of
      chronic sinus disease and have led to new surgical techniques. Functional
      endoscopic sinus surgery (FESS), a new surgical approach to chronic sinus
      disease, seems to have promising results in the treatment of chronic sinusitis as
      compared to prior traditional techniques.

PMID- 8558577
TI  - Sinusitis and headache.
AB  - The association of headache and sinusitis was studied in 207 patients who
      underwent surgery for chronic sinusitis that failed to respond to medical
      management. Sixty-nine percent of the patients had headaches and 31% did not. In
      9% headache was the only symptom and the diagnosis of sinusitis was made on
      clinical and/or CT grounds. The pain was usually pressure in character, moderate
      in intensity and lasted for hours. Its location usually, but not always, pointed
      to the sinuses involved. Discreet sphenoid or ethmoid disease discovered on
      imaging may be responsible for midline pains. Sinusitis may also trigger or
      aggravate vascular headaches.

PMID- 8558578
TI  - Advances in otology and neurotology.
AB  - During the last few years many advances occurred in the field of Otolaryngology.
      In this article we will present significant advances in the fields of otology and
      neurotology. The adaptation of laser energy to surgery is a significant event in
      the evolution of ear microsurgery. Lasers in otology reduce trauma and increase
      accuracy. Implantable hearing devices are used to rehabilitate patients with mild
      to moderately severe hearing loss. Cochlear implants have secured a permanent
      role in the management of selected profoundly deaf patients. Intraoperative
      cranial nerve monitoring is a major advance in ear surgery. Facial nerve and
      auditory nerve monitoring are now widely used and are the basis for facial and
      hearing conservation.

PMID- 8558579
TI  - Skull base surgery: an emerging new specialty.
AB  - The field of Skull base Surgery evolved rapidly over the past several years. The
      techniques that were developed now make it possible to treat lesions that were
      previously deemed inaccessible. This article is a review of some of the aspects
      of this evolving specialty. Three representative cases will be presented and
      discussed with special emphasis on patient selection, surgical complications and
      postoperative rehabilitation.

PMID- 8558580
TI  - Diagnosis of head and neck cancer.
AB  - The diagnosis of cancer of the head and neck may at times be obvious on clinical
      presentation. In certain situations, however, this may be a dilemma for the
      clinician and the pathologist. In addition to establishing a pathologic diagnosis
      of squamous cell carcinoma of the head and neck, the work-up of these patients
      aims at delineating the exact extent of disease. This has important therapeutic
      and prognostic implications. This review will outline the diagnostic steps in
      head and neck cancer patients. These include a thorough history and physical
      examination, laboratory evaluation, imaging modalities, endoscopic biopsy and
      fine needle aspiration.

PMID- 8558581
TI  - Head and neck cancer: state of the art.

PMID- 8558582
TI  - Pediatric stridor and airway compromise.
AB  - Technological advances in optics, laser, anesthesia, and radiology have improved
      our ability to diagnose and treat airway obstruction in the very young.
      Concomitant advances in neonatology and critical care have led to an increase in
      laryngeal and tracheal stenosis secondary to prolonged endotracheal intubation.
      This manuscript presents a summary of the management of many common pediatric
      airway diseases.

PMID- 8558583
TI  - Middle ear effusion.
AB  - Acute otitis media and middle ear effusion are among the most common illnesses of
      childhood. Accuracy in identification and diagnoses, and awareness of the
      epidemiologic risk factors, the resultant hearing loss and possible language
      impairment are of paramount importance to the pediatrician and otolaryngologist
      alike. The goals of management are prompt and effective treatment and follow up
      to restore hearing and avoid speech and language impairment and other long term
      sequelae.

PMID- 8558584
TI  - Adenotonsillar disease.
AB  - Adenotonsillar disease can be divided into two categories, infection and
      hypertrophy. They are closely related with low grade infection causing
      hypertrophy in most instances. Minor advances have been accomplished in the
      treatment of infectious processes, mainly the advent of new antibiotics. More
      important advances have occurred in the field of airway obstruction secondary to
      adenotonsillar hypertrophy. Currently there exists a significant body of
      knowledge on obstructive sleep apnea. With improvement in anesthetic and surgical
      techniques younger children are being treated earlier to relief airway
      obstruction. This manuscript describes current management of adenotonsillar
      disease.

PMID- 8558585
TI  - Management of upper airway obstruction: intubation vs tracheotomy.
AB  - Management of the obstructed upper airway may be very challenging. It requires
      careful clinical evaluation as well as supportive laboratory data and physiologic
      monitoring. A team approach is essential. This paper is an overall review of the
      subject of airway control intended to guide health care providers dealing with
      such patients. Various options of intervention including endotracheal intubation,
      tracheotomy and transtracheal jet ventilation are discussed. The indications,
      advantages, disadvantages and potential complications of each of these methods
      are detailed. Recent advances in this field are described such as new tube
      material and technology, non-invasive physiologic monitoring (oxygen saturation
      measurements) and modifications of the surgical techniques.

PMID- 8558586
TI  - Recent advances in facial plastic and reconstructive surgery.
AB  - The evolving world of facial plastic and reconstructive surgery has, as in any
      other specialty or subspecialty, seen new trends and experienced tremendous
      bounds. In this review they will be discussed under two headings: cosmetic
      surgery and reconstructive surgery. The aim of this paper is to help educate the
      nonspecialist about the most significant recent advances.

PMID- 8558587
TI  - Lasers in otorhinolaryngology-head and neck surgery.
AB  - Lasers have been used in otorhinolaryngology for more than 2 decades. The Carbon
      Dioxide laser has been the ideal choice for many otolaryngologists, in addition
      to the Nd:YAG, KTP, and Argon lasers. Each of the presently available lasers has
      it benefits and limitations. Advances in laser technology, new laser wavelengths,
      and delivery systems provides more choices for clinical use. A review of the uses
      of lasers in otology, rhinology and head and neck surgery, and advances in
      technology is presented. The advantages, limitations, tissue interaction,
      complications, present, and future clinical applications are discussed.

PMID- 8558588
TI  - Inhibition of Na(+)-pump expression by impairment of protein glycosylation is
      independent of the reduced sodium entry into the cell.
AB  - Previous studies indicate that inhibition of protein N-glycosylation reduces
      Na(+)-pump activity. Since this effect is preceded by an inhibition of the entry
      of sodium into the cell, it is unclear whether the reduced Na(+)-pump is produced
      by the inactivation of protein glycosylation per se or by the lower intracellular
      sodium concentration. We compared the effects of tunicamycin, which inhibits
      protein glycosylation, and amiloride, which inhibits the entry of sodium into the
      cell, on the expression of the Na(+)-pump activity in A6 cells. The short-circuit
      current across A6 epithelia, which corresponds to sodium ions transported through
      the Na+ channel and the Na(+)-pump, was almost totally inhibited after 24-hr
      treatment with 1 microgram/ml tunicamycin. The maximal Na(+)-pump activity,
      measured after permeabilizing the apical cell membrane with amphotericin B, was
      only 30% inhibited. This inhibition increased to 80% after 72-hr treatment with
      tunicamycin. Thus, tunicamycin inhibits the activities of both the apical Na+
      channel and the basolateral Na(+)-pump. However, the reduced number of Na(+)-pump
      molecules, as well as the inhibition of the Na(+)-pump activity, were not
      observed when the Na+ channel was inhibited for 72-hr with amiloride. Thus, the
      reduced Na(+)-pump expression produced by inactivation of protein glycosylation
      is not secondary to reduced entry of sodium into the cell.

PMID- 8558589
TI  - Low conductance states of a single ion channel are not 'closed'.
AB  - We have used a polymer-exclusion method to estimate the sizes of the high- and
      low-conductance states of Staphylococcus aureus alpha-toxin channels across
      planar lipid bilayers. Despite a > 10-fold difference in conductance between high
      and low-conductance states, the size differs by < 2-fold. We conclude that
      factors other than the dimensions have a strong influence on the conductance of
      alpha-toxin channels. We also show that the high conductance state is
      destabilized by the presence of high molecular weight polymers outside the
      channel, compatible with the removal of channel water as the high conductance
      state "shrinks" to the low conductance state.

PMID- 8558590
TI  - Modulation of the serotonin-activated K+ channel by G protein subunits and
      nucleotides in rat hippocampal neurons.
AB  - In hippocampal neurons, 5-hydroxytryptamine (5-HT) activates an inwardly
      rectifying K+ current via G protein. We identified the K+ channel activated by 5
      HT (K5-HT channel) and studied the effects of G protein subunits and nucleotides
      on the K+ channel kinetics in adult rat hippocampal neurons. In inside-out
      patches with 10 microM 5-HT in the pipette, application of GTP (100 microM) to
      the cytoplasmic side of the membrane activated an inwardly rectifying K+ channel
      with a slope conductance of 36 +/- 1 pS (symmetrical 140 mM K+) at -60 mV and a
      mean open time of 1.1 +/- 0.1 msec (n = 5). Transducin beta gamma activated the
      K5-HT channels and this was reversed by alpha-GDP. Whether the K5-HT channel was
      activated endogenously (GTP, GTP gamma S) or exogenously (beta gamma), the
      presence of 1 mM ATP resulted in a approximately 4-fold increase in channel
      activity due in large part to the prolongation of the open time duration. These
      effects of ATP were irreversible and not mimicked by AMPPMP, suggesting that
      phosphorylation might be involved. However, inhibitors of protein kinases A and C
      (H-7, staurosporine) and tyrosine kinase (tyrphostin 25) failed to block the
      effect of ATP. These results show that G beta gamma activates the G protein-gated
      K+ channel in hippocampal neurons, and that ATP modifies the gating kinetics of
      the channel, resulting in increased open probability via as yet unknown pathways.

PMID- 8558591
TI  - The pH-sensitivity of transepithelial K+ transport in vestibular dark cells.
AB  - The pH-sensitivity of transepithelial K+ transport was studied in vitro in
      isolated vestibular dark cell epithelium from the gerbil ampulla. The cytosolic
      pH (pHi) was measured microfluorometrically with the pH-sensitive dye 2',7'
      bicarboxyethyl-5(6)-carboxyfluorescein (BCECF) and the equivalent short-circuit
      current (Isc), which is a measure for transepithelial K+ secretion, was
      calculated from measurements of the transepithelial voltage (Vt) and the
      transepithelial resistance (Rt) in a micro-Ussing chamber. All experiments were
      conducted in virtually HCO3(-)-free solutions. Under control conditions, pHi was
      7.01 +/- 0.04 (n = 18), Vt was 9.1 +/- 0.5 mV, Rt 16.7 +/- 0.09 omega cm2, and
      Isc was 587 +/- 30 microA/cm2 (n = 49). Addition of 20 mM propionate- caused a
      biphasic effect involving an initial acidification of pHi, increase in Vt and Isc
      and decrease in Rt and a subsequent alkalinization of pHi, decrease of Vt and
      increase of Rt. Removal of propionate- caused a transient effect involving an
      alkalinization of pHi, a decrease of Vt and Isc and an increase in Rt, pHi in the
      presence of propionate- exceeded pHi under control conditions. Effects of
      propionate- on Vt, Rt and Isc were significantly larger when propionate- was
      applied to the basolateral side rather than to the apical side of the epithelium.
      The pHi-sensitivity of Isc between pH 6.8 and 7.5 was -1089 microA/(cm2.pH-unit)
      suggesting that K+ secretion ceases at about pHi 7.6. Acidification of the
      extracellular pH (pHo) caused an increase of Vt and Isc and a decrease of Rt most
      likely due to acidification of pHi. Effects were significantly larger when the
      extracellular acidification was applied to the basolateral side rather than to
      the apical side of the epithelium. The pHo sensitivity of Isc between pH 7.4 and
      6.4 was -155 microA/(cm2.pH unit). These results demonstrate that transepithelial
      K+ transport is sensitive to pHi and pHo and that vestibular dark cells contain
      propionate- uptake mechanism. Further, the data suggest that cytosolic
      acidification activates and that cytosolic alkalinization inactivates the slowly
      activating K+ channel (IsK) in the apical membrane. Whether the effect of pHi on
      the IsK channel is a direct or indirect effect remains to be determined.

PMID- 8558592
TI  - Hypo-osmotic challenge stimulates transepithelial K+ secretion and activates
      apical IsK channel in vestibular dark cells.
AB  - Volume regulation of vestibular dark cells from the gerbilline inner ear in
      response to a hypo-osmotic challenge depends on the presence of cytosolic K+ and
      Cl-. The present study addresses the questions: (i) whether and by what mechanism
      K+ is released during volume regulation, (ii) whether the osmolarity of the
      basolateral medium has an effect on the steady-state rate of transepithelial K+
      transport and (iii) whether there is cross-talk between the basolateral membrane
      responsible for K+ uptake and the apical membrane responsible for K+ release. K+
      secretion (JK+,probe) and current density (Isc,probe) were measured with
      vibrating probes in the vicinity of the apical membrane and the transepithelial
      potential (Vt) and resistance (Rt) were measured in a micro-Ussing chamber. The
      equivalent short-circuit current (Isc) was calculated. The current (IIsK),
      conductance (gIsK) and inactivation time constant (tau IsK) of the IsK channel
      and the apparent reversal potential of the apical membrane (Vr) were obtained
      with the cell-attached macropatch technique. Vr was corrected (Vrc) for the
      membrane voltage (Vm) measured separately with microelectrodes. A hypo-osmotic
      challenge (294 to 154 mosM by removal of 150 mM mannitol) on the basolateral side
      of the epithelium increased JK+,probe and Isc,probe by a factor of 2.7 and 1.6.
      When this hypo-osmotic challenge was applied to both sides of the epithelium Vt
      and Isc increased from 5 to 14 mV and from 189 to 824 microA/cm2 whereas Rt
      decreased from 27 to 19 omega-cm2. With 3.6 mM K+ in the pipette IIsK was
      outwardly directed, tau IsK was 267 msec and the hypo-osmotic challenge caused
      IIsK and gIsK to increase from 14 to 37 pA and from 292 to 732 pS. Vrc
      hyperpolarized from -44 to -76 mV. With 150 mM K+ in the pipette IIsK was
      inwardly directed, tau IsK was 208 msec and the hypo-osmotic challenge caused
      IIsK and gIsK to increase in magnitude from 0 to -21 pA and from 107 to 1101 pS.
      Vrc remained unchanged (-2 vs. 1 mV). These data demonstrate that a hypo-osmotic
      challenge stimulates transepithelial K+ secretion and activates the apical IsK
      channel. The hypo-osmotically-induced increase in K+ secretion exceeded the
      estimated amount of K+ release necessary for the maintenance of constant cell
      volume, suggesting that the rate of basolateral K+ uptake was upregulated in the
      presence of the hypo-osmotic challenge and that cross-talk exists between the
      apical membrane and the basolateral membrane.

PMID- 8558593
TI  - Spatial organization of transport domains and subdomain formation in the plasma
      membrane of Chara corallina.
AB  - Pattern formation mechanisms in developing organisms determine cellular
      differentiation and function. However, the components that interact during the
      manifestation of a spatial pattern are in general unknown. Characean algae
      represent a model system to study pattern formation. These algae develop
      alternating acid and alkaline transport domains that influence the pattern of
      growth. In the present study, it will be demonstrated that a diffusion mechanism
      is implicated in acid and alkaline domain formation and this growth pattern.
      Experiments on the characean growth pattern were performed that resulted in
      pronounced, however, unpredictable modifications in the original pattern. A major
      component involved in this pattern-forming mechanism emerged from the nonlinear
      kinetics of the H(+)-ATPase that is located in the plasma membrane of these
      algae. Based on these kinetics, a mathematical model was developed and
      numerically analyzed. As a result, the contribution of a diffusional component to
      the characean acid/alkaline pattern appeared most likely.

PMID- 8558594
TI  - Modulation of a volume-regulated chloride current by F-actin.
AB  - We have examined whether F-actin integrity is involved in activation of a volume
      regulated Cl- current (VRChlC) in B-lymphocytes. VRChlC activation was initiated
      in response to establishing a whole cell recording in the presence of a
      hyposmotic gradient. Parallel confocal microscopy experiments using Rhodamine
      Phalloidin (R-P) as a specific marker of F-actin showed that the submembrane
      actin ring is reversibly disrupted in response to an hyposmotic gradient.
      Disruptions of cortical F-actin integrity by 50 microM cytochalasin B (CB) does
      not trigger activation of VRChlC under isosmotic conditions or potentiate the
      rate of activation when the osmolarity of the extracellular solution was
      decreased by 75%. However, incubation with CB increased the rate of VRChlC
      activation in response to a 90% hyposmotic gradient. Phalloidin, a stabilizer of
      F-actin, decreases the rate of VRChlC activation in response to a 90% gradient,
      but has no effect in response to a 75% gradient. These observations suggest that
      disassembly of cortical F-actin is not critical for VRChlC activation in B
      lymphocytes. The integrity of cortical F-actin, however, can exert a modulatory
      effect on the rate of VRChlC activation in the presence of a hyposmotic gradient.

PMID- 8558595
TI  - Evidence for Na-K-Cl cotransport in alveolar epithelial cells: effect of phorbol
      ester and osmotic stress.
AB  - We have investigated the presence of Na-K-Cl cotransport in alveolar type II
      cells using uptake of 86Rb. Several data support the presence of a Na-K-Cl
      cotransport in these cells. First, a large fraction of ouabain-resistant 86Rb
      uptake was inhibited by bumetanide and furosemide. Second, bumetanide-sensitive
      86Rb uptake required the presence of Na+ and Cl- in the incubation medium;
      dependency on extracellular Na+ and K+ was hyperbolic, with a Km of 14.6 mM and
      8.3 mM, respectively, while dependency on extracellular Cl- was sigmoidal, which
      suggests a 1:1:2 stoichiometry. Third, a fraction of amiloride-insensitive 22Na
      influx was deeply inhibited by bumetanide. 22Na influx was dependent on the
      presence of extracellular K+ and Cl-. Since Na-K-Cl activity dramatically
      decreased with time in culture, further characterization of the cotransport on
      polarized cells could not be performed. The phorbol ester PMA inhibited Na-K-Cl
      cotransport in a time- and concentration-dependent manner. This inhibition was
      mimicked by oleoylacetylglycerol, dioctanoylglycerol, and the diacylglycerol
      kinase inhibitor R59022, and was reversed by an antagonist of PKC, staurosporine.
      Since the Na-K-Cl cotransport has been reported to be involved in cell volume
      regulation, we investigated its modulation by changes in extracellular
      osmolarity. Na-K-Cl activity was increased after a two-step procedure: swelling
      in hypotonic medium followed by shrinking in hypertonic medium. Under these
      conditions, cotransport activity increased whenever PKC activity was up- or
      downregulated, which suggests that the cell volume-induced modulation of the
      cotransport is independent from the PKC activity. Though we were not able to
      determine the polarity of the cotransport, it may also be involved in the
      absorptive function of alveolar type II cells, and would provide an alternate
      pathway for sodium entry.

PMID- 8558596
TI  - Human macrophages contain a stretch-sensitive potassium channel that is activated
      by adherence and cytokines.
AB  - A variety of stimuli, including cytokines and adhesion to surfaces and matrix
      proteins, can regulate macrophage function, in part through changes in Ca(2+)-
      dependent second messengers. While fluctuation in intracellular Ca2+ is an
      important modulator of cellular activation, little attention has been paid to the
      roles of other ions whose cytoplasmic concentrations can be rapidly regulated by
      ion channels. To examine the role of ion channels in macrophage function, we
      undertook patch clamp studies of human culture-derived macrophages grown under
      serum-free conditions. The major ionic current in these cells was carried by an
      outwardly rectifying K+ channel, which had a single-channel conductance of 229 pS
      in symmetrical K(+)-rich solution and macroscopic whole-cell conductance of 9.8
      nS. These channels opened infrequently in resting cells but were activated
      immediately by (i) adhesion of mobile cells onto a substrate, (ii) stretch
      applied to isolated membrane patches in Ca(2+)-free buffers, (iii) intracellular
      Ca2+ (EC50 of 0.4 microM), and (iv) the cytokine IL-2. Furthermore, barium and 4
      aminopyridine, blockers of this channel, altered the organization and structure
      of the cytoskeletal proteins actin, tubulin and vimentin. These cytoskeletal
      changes were associated with reversible alteration to the morphology of the
      cells. Thus, we have identified an outwardly rectifying K+ channel that appeared
      to be involved in cytokine and adherence-mediated macrophage activation, and in
      the maintenance of cytoskeletal integrity and cell shape.

PMID- 8558598
TI  - Lysozyme acts as a chemorepellent and secretagogue in Paramecium by activating a
      novel receptor-operated Ca++ conductance.
AB  - Using combined intracellular recordings and behavioral bioassays, it was found
      that lysozyme has two different effects in Paramecium, depending upon the
      concentrations used. At low concentrations (0.5 mM to 1.0 microM) it acts as an
      effective chemorepellent that causes reliable electrophysiological changes.
      Lysozyme-induced somatic depolarizations, isolated by blocking K+ channels with
      Cs-TEA, showed concentration dependencies that were well correlated with
      chemorepulsion. Ion dependency experiments showed that these were Ca++ based
      depolarizations. Addition of either Na+ or Mg++ improves chemorepulsion by
      providing additional depolarizations. Both the depolarizations and chemorepulsion
      were blocked by 10 microM neomycin, suggesting that the depolarization is
      necessary for this chemosensory transduction event. At higher concentrations (100
      microM), lysozyme is a secretagogue. A transient inward current, recorded in Ca++
      alone solutions with Cs-TEA present, was seen in response to high lysozyme
      concentrations. The amplitude of this inward current was well correlated with
      exocytosis. Addition of neomycin (1.0 mM) eliminated both the inward current and
      exocytosis, suggesting a causal relationship. Neither amiloride or W-7, compounds
      previously suggested to affect the electrophysiological responses to
      secretagogues, had any significant effects. The mucopolysaccharide hydrolysis
      activity of lysozyme was not required for any of these responses. We propose that
      Paramecium have a high affinity receptor on the body plasma membrane that
      responds to either lysozyme or a related compound to cause an increase in a novel
      body Ca++ conductance. This receptor-operated Ca++ conductance causes membrane
      depolarization and chemorepulsion at low concentrations and triggers a sufficient
      Ca++ influx at high concentrations to cause exocytosis.

PMID- 8558597
TI  - pH- and voltage-dependent conductances in toad skin.
AB  - The present study focuses on two closely related topics on ion conductance in
      toad skins: (i) the interaction of apical protons with the apical voltage
      dependent Cl(-)-activated channels of the mitochondria-rich cells, and (ii) the
      description and characterization of a novel subject, a voltage-dependent H(+)
      activated conductance. The Cl- conductance (GCl) is activated by tissue
      hyperpolarization (which leads to apical membrane depolarization) and the
      presence of Cl- ions in the apical solution. Increasing apical proton
      concentration (from pH 8 to pH 4) impairs the process of activation of the Cl-
      conductive pathway, slowing the kinetics of It activation and reducing the steady
      stage values of Gt and It. This effect is markedly voltage-dependent since no
      effect is seen at Vt = -100 mv and is fully present at -50 mV. The voltage
      dependence of the pH effect suggests that the critical protonation sites of the
      apical Cl- channels are not freely exposed to the apical solution but dwell
      within the membrane electric field. An also coherent interpretation is that
      titration of apical proton binding sites affects the gating of the voltage
      dependent Cl- channels, shifting the conductance-vs.-voltage curve to more
      negative clamping potentials. Tissue conductance in the absence of apical Cl-
      ions can be importantly affected by the pH of the apical solution (pHa), the
      effect being markedly dependent on the clamping potential. Generally speaking,
      the effect of rising apical proton concentration can be conspicuous at negative
      clamping potentials, while at positive potentials changes in tissue conductance
      were never observed. For a clamping potential of -100 mV, a turning point
      somewhere between pHa = 4 and pHa = 3 was observed. Apical acidification to pH 4
      has no effect upon tissue conductance while apical acidification to pH 3 leads to
      a marked, slow and reversible increase of tissue conductance. A striking
      similitude exists between the voltage-dependent Cl(-)-gated conductance and the
      voltage-dependent proton-gated conductance regarding: (i) slow time courses of
      activation and deactivation, (ii) requirement for a negative clamping potential
      and the presence of a specific ion species in the apical solution for activation
      to take place, (iv) instantaneous ohmic behavior, and (v) steady-state
      rectification. However, so far the results do not permit one to conclude
      definitely that the voltage-dependent Cl(-)-gated conductance and the voltage
      dependent proton-gated conductance share a common pathway.

PMID- 8558599
TI  - Membrane fatty acid composition of tissues is related to body mass of mammals.
AB  - Phospholipids were extracted from tissues (heart, skeletal muscle, kidney cortex,
      liver and brain) of mammals representing a 9,000-fold range in body mass (mouse,
      rat, rabbit, sheep and cattle) and their fatty acid composition was determined.
      In heart, skeletal muscle and kidney cortex, there were significant allometric
      decreases in the Unsaturation Index (UI; average number of double bonds per 100
      fatty acid molecules) with increasing body mass. There were significant inverse
      allometric relationships between body mass and the proportion of docosahexaenoic
      acid (22:6 omega 3) in heart and skeletal muscle. In heart, skeletal muscle and
      kidney cortex, larger mammals also had shorter fatty acid chains in their
      phospholipids and a higher proportion of monounsaturates. In liver, smaller
      mammals had a higher UI than larger mammals (except the rabbit, which had the
      lowest UI and very low proportions of omega 3 fatty acids). The brain of all
      mammals maintained a high UI with similar levels of polyunsaturated fatty acids,
      especially 22:6 omega 3. Our results suggest that in heart, skeletal muscle and
      kidney cortex the activity of the elongases and desaturases are reduced in large
      mammals compared to small mammals. The allometric trends in membrane composition
      may be involved in modifying membrane permeability. It is proposed that the
      elevated degree of polyunsaturation in the membranes of several tissues from
      small mammals is related to their higher metabolic activity.

PMID- 8558600
TI  - A Cl channel in Ascaris suum selectivity conducts dicarboxylic anion product of
      glucose fermentation and suggests a role in removal of waste organic anions.
AB  - The permeability of organic anions (produced anaerobic fermentation of glucose)
      through a non-selective membrane Cl channel was examined. Single channel
      recording techniques were used to study the permeabilities of the anions:
      oxalate, succinate, oxaloacetate, malate, lactate and pyruvate in Ascaris muscle
      cell membranes. All of the anions, except malate, were found to be conducted
      through the channel. The relative permeability of most anions could be predicted
      from the component structure of the anions. The failure of the channel to conduct
      malate prevents an energy drain on the cell. These studies further the hypothesis
      that a Cl channel functions to transport waste organic anions across the cell
      membrane. This mechanism does not require specific exchange carriers for the
      anions. Channels with properties like the nonselective anion channels of Ascaris,
      are suitable for transport of carboxylic anions through cell membranes, down a
      concentration or potential gradient.

PMID- 8558601
TI  - The expression of Na+/K(+)-ATPase beta-subunit cRNA injected into Xenopus oocytes
      is affected by coinjection with alpha-subunit cRNA.
AB  - The cRNA for Torpedo californica Na+/K(+)-ATPase beta-subunit (cRNA beta) was
      injected into Xenopus oocytes alone or with the cRNA for the Na+/K(+)-ATPase
      alpha-subunit (cRNA alpha). When cRNA beta was injected alone, the amount of the
      beta-subunit that accumulated in oocytes increased with increasing amounts of
      injected cRNA beta. When cRNA beta and cRNA alpha were injected simultaneously,
      less beta-subunit accumulated than when cRNA beta was injected alone, whereas the
      Na+/K(+)-ATPase activity increased markedly. The decrease in the accumulation of
      the beta-subunit was dose-dependent upon the cRNA alpha. The mutant beta-subunit
      unable to assemble with the alpha-subunit accumulated in oocytes independently of
      cRNA alpha, suggesting that post-translational control mechanisms may serve to
      reduce the accumulation of the beta-subunit.

PMID- 8558602
TI  - Ionic permeabilities induced by Bacillus thuringiensis in Sf9 cells.
AB  - The effect of Bacillus thuringiensis insecticidal toxins on the monovalent cation
      content and intracellular pH (pHi) of individual Sf9 cells of the lepidopteran
      species Spodoptera frugiperda (fall armyworm) was monitored with the fluorescent
      indicators potassium-binding benzofuran isophthalate (PBFI) and 2',7'
      bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). The sequential removal of K+
      and Na+ from the medium, in the presence of CryIC, a toxin which is highly active
      against Sf9 cells, caused sharp shifts in the fluorescence ratio of PBFI,
      demonstrating a rapid efflux of these ions. In Sf9 cells, pHi depends strongly on
      the activity of a K+/H+ exchanger. In the absence of toxin, removal of K+ from
      the external medium resulted in a reversible acidification of the cells. In the
      presence of CryIC, pHi equilibrated rapidly with that of the bathing solution.
      This effect was both time- and concentration-dependent. In contrast with CryIC,
      CryIIIA, a coleopteran-specific toxin, and CryIA(a), CryIA(b) and CryIA(c),
      toxins which are either inactive or poorly active against Sf9 cells, had no
      detectable effect on pHi. B. thuringiensis endotoxins thus appear to act
      specifically by increasing the permeability of the cytoplasmic membrane of
      susceptible cells to at least H+, K+ and Na+.

PMID- 8558604
TI  - Correlation of open cell-attached and excised patch clamp techniques.
AB  - The excised patch clamp configuration provides a unique technique for some types
      of single channel analyses, but maintenance of stable, long-lasting preparations
      may be confounded by rundown and/or rapid loss of seal. Studies were performed on
      the amiloride-sensitive Na+ channel, located on the apical surface of A6 cells,
      to determine whether the nystatin-induced open cell-attached patch could serve as
      an alternative configuration. Compared to excised inside-out patches, stable
      preparations were achieved more readily with the open cell-attached patch (9% vs.
      56% of attempts). In both preparations, the current voltage (I-V) relation was
      linear, current amplitudes were equal at opposite equivalent clamped voltages,
      and Erev was zero in symmetrical Na+ solutions, indicating similar Na+ activities
      on the cytosolic and external surfaces of the patch. Moreover, there was no
      evidence that nystatin altered channel activity in the patch because slope
      conductance (3-4pS) and Erev (75 mV), when the bath was perfused with a high
      K:low Na solution (ENa = 80 mV), were nearly equal in both patch configurations.
      Our results therefore indicate that the nystatin-induced open cell-attached patch
      can serve as an alternative approach to the excised inside-out patch when
      experiments require modulation of univalent ions in the cytosol.

PMID- 8558603
TI  - A method for determining the unitary functional capacity of cloned channels and
      transporters expressed in Xenopus laevis oocytes.
AB  - The Xenopus laevis oocyte is widely used to express exogenous channels and
      transporters and is well suited for functional measurements including currents,
      electrolyte and nonelectrolyte fluxes, water permeability and even enzymatic
      activity. It is difficult, however, to transform functional measurements recorded
      in whole oocytes into the capacity of a single channel or transporter because
      their number often cannot be estimated accurately. We describe here a method of
      estimating the number of exogenously expressed channels and transporters inserted
      in the plasma membrane of oocytes. The method is based on the facts that the P
      (protoplasmic) face in water-injected control oocytes exhibit an extremely low
      density of endogenous particles (212 +/- 48 particles/microns2, mean, SD) and
      that exogenously expressed channels and transporters increased the density of
      particles (up to 5,000/microns2) only on the P face. The utility and generality
      of the method were demonstrated by estimating the "gating charge" per particle of
      the Na+/glucose cotransporter (SGLT1) and a nonconducting mutant of the Shaker K+
      channel proteins, and the single molecule water permeability of CHIP (Channel
      like In-tramembrane Protein) and MIP (Major Intrinsic Protein). We estimated a
      "gating charge" of approximately 3.5 electronic charges for SGLT1 and
      approximately 9 for the mutant Shaker K+ channel from the ratio of Qmax to
      density of particles measured on the same oocytes. The "gating charges" were 3
      fold larger than the "effective valences" calculated by fitting a Boltzmann
      equation to the same charge transfer data suggesting that the charge movement in
      the channel and cotransporter occur in several steps. Single molecule water
      permeabilities (pfs) of 1.4 x 10(-14) cm3/sec for CHIP and of 1.5 x 10(-16)
      cm3/sec for MIP were estimated from the ratio of the whole-oocyte water
      permeability (Pf) to the density of particles. Therefore, MIP is a water
      transporter in oocytes, albeit approximately 100-fold less effective than CHIP.

PMID- 8558607
TI  - A 12 month study of Syphilis. Sexually transmitted diseases in a university
      student population.

PMID- 8558605
TI  - Effects of internal pH on the nonselective cation channel from the mouse
      collecting tubule.
AB  - We investigated the effects of internal pH on Ca-activated, nucleotide-inhibited
      nonselective cation channels in the basolateral membranes of mouse collecting
      tubules, using the inside-out variant of the patch clamp technique. pH modulated
      the channel open probability (Po), giving a bell-shaped curve peaking at pH
      6.8/7.0: Po at pH 6.0 was 11 +/- 6% of Po at pH 7.2 and 32 +/- 7% at pH 8.0. The
      open and closed time distributions, best fitted to the sum of two exponentials,
      were differently sensitive to acid and alkaline conditions. Low pH reduced the
      short and long open times to 38 and 24% of their pH 7.2 values, while high pH
      produced a 4-fold increase in the long closed time. As previously reported, 4
      acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) induced a quasi
      permanent opening of the channel. The inhibition of the channel produced by high
      pH disappeared in the presence of SITS, while the inhibition produced by low pH
      was unaffected. These results suggest that the pH dependence of the channel is
      due to two separate mechanisms. pH was without effect on the ATP-evoked
      inhibition of the channel, while high pH profoundly reduced the steepness of the
      AMP inhibition curve, without altering the half-maximal inhibitory AMP
      concentration.

PMID- 8558606
TI  - Selectivity of ATP-activated GTP-dependent Ca(2+)-permeable channels in rat
      macrophage plasma membrane.
AB  - Outside-out configuration of the patch clamp technique was used to test whether
      an intracellular application of G protein activator (GTP gamma S) affects ATP
      activated Ca(2+)-permeable channels in rat macrophages without any agonist in the
      bath solution. With 145 mM K+ (pCa 8.0) in the pipette solution, activity of
      channels permeable to a variety of divalent cations and Na+ was observed and
      general channel characteristics were found to be identical to those of ATP
      activated ones. Absence of extracellular ATP makes it possible to avoid the
      influence of ATP receptor desensitization and to study the channel selectivity
      using a number of divalent cations (105 mM) and Na+ (145 mM) as the charge
      carriers. Permeability sequence estimated by extrapolated reversal potential
      measurements was: Ca2+:Ba2+:Mn2+:Sr2+: Na+:K+ = 68:30:26:10:3.5:1. Slope
      conductances (in pS) for permeant ions rank as follows: Ca2+:Sr2+: Na+:Mn2+:Ba2+
      = 19:18:14:12:10. Unitary Ca2+ currents display a tendency to saturate with the
      Ca2+ concentration increase with apparent dissociation constant (Kd) of 10 mM. No
      block of Na+ permeation by extracellular Ca2+ in millimolar range was found. The
      data obtained suggest that (i) activation of some G protein is sufficient to gate
      the channels without the ATP receptor being occupied, (ii) the ATP receptor
      activation results in the gating of a special channel with the properties that
      differ markedly from those of the receptor-operated or voltage-gated Ca(2+)
      permeable channels on the other cell types.

PMID- 8558608
TI  - Candida as a nail pathogen in healthy patients.

PMID- 8558609
TI  - AMA and USP seek physician assistance in preventing medication errors.

PMID- 8558610
TI  - AMA survey--American's know little or nothing about health care advance
      directives.

PMID- 8558611
TI  - America's failure to use advance directives--helping your patients shape their
      health care future.

PMID- 8558612
TI  - The fourth epoch.

PMID- 8558613
TI  - Case records of the University of the Department of Medicine University of
      Mississippi Medical Center. Polyarteritis nodosa.

PMID- 8558614
TI  - House makes correct diagnosis, offers wrong cure for Medicare/Medicaid.

PMID- 8558615
TI  - Affirmative action politics: the shotgun plan revisited.

PMID- 8558616
TI  - Psychosocial/cultural issues in medicine and psychiatry: treating African
      Americans.
AB  - In general, we are raised in a specific cultural environment, and consequently,
      we have a common sense of identity, shared standards, and religion. The effects
      of this commonality carries over into health-care situations, including health
      maintenance and disease prevention. This article provides an overview of how
      psychosocial/cultural issues have been used with insensitivity to race, culture,
      and the value orientations of African Americans. It is concluded that the
      training of all health-care practitioners should include psychosocial/cultural
      aspects of illnesses.

PMID- 8558617
TI  - Maternal reports of behavior problems in preschool Hispanic children: an
      exploratory study in preventive pediatrics.
AB  - Maternal reports on the health, behavioral, and educational characteristics of
      Hispanic low-income preschoolers were gathered from a pediatric clinic to conduct
      appropriate consultation and teaching of behavioral issues to pediatric
      residents. Fifty-two Hispanic mothers attending an urban hospital clinic were
      given a questionnaire. Interviews provided data on family demographics,
      children's health status, behavior problems (65 items adapted from Achenbach's
      1981 and 1987 Child Behavior Checklists [CBCL]), maternal depression, family life
      stressful events, and discipline methods. Thirteen externalizing and five
      internalizing high frequency behaviors were identified. Behavior problem scores
      were significantly related to the use of yelling and hitting/spanking as methods
      of discipline. Precarious health status and low enrollment in preschool programs
      also were reported. A broader preventive role for pediatricians in that pediatric
      setting was recommended and pursued. Results suggest a broad preventive role for
      pediatricians and pediatric clinics servicing low-income preschoolers.

PMID- 8558618
TI  - Role of platelet age in assessment of coagulation.
AB  - There are two important reasons why most platelet function studies can be
      inaccurate. First, platelet function deteriorates when blood is taken out of the
      vascular tree. Second, tests performed on platelets removed from the blood do not
      incorporate the role of other cellular and chemical components that may alter
      platelet activity. This article demonstrates that a coagulation test developed in
      our laboratory can accurately assess the role of platelet age on the speed of the
      coagulation of blood. Samples (5.0 mL) of citrated venous blood from 15
      volunteers were divided into two groups. One group (n = 6), comprised of
      subgroups A, B, C, and D of 950 microL aliquots each, was tested within 3 hours.
      The second group (n = 9), comprised of subgroups E, F, G, and H of 950 microL
      aliquots each, was tested at 24 hours. The aliquots were added to 50 microL
      saline without collagen (subgroups A and E), 50 microL saline with 10 micrograms
      collagen (subgroups B and F), 50 microL saline with 50 micrograms collagen
      (subgroups C and G), and 50 microL saline with 100 micrograms collagen (subgroups
      D and H). All collagen-incubated fresh blood samples were significantly more
      hypercoagulable (shorter recalcification times) compared with the control (no
      collagen) blood. In the 24-hour-old blood, changes were significant only in the
      sample with 50 micrograms/mL collagen. We conclude that these data authenticate
      the role of platelet age in the assessment of the coagulation process.

PMID- 8558619
TI  - Misdiagnosis among older psychiatric patients.
AB  - The first 13 consecutive referrals to a newly established Geriatric Psychiatry
      Research Division (GPRD) at a community mental health center (CMHC) in Baltimore,
      Maryland, were evaluated with the structured clinical interview (SCID) from the
      third edition of the Diagnostic and Statistical Manual, Revised (DSM-III-R).
      Although the referring primary diagnoses were confirmed in 54% of patients (7 of
      13), an average of three new diagnoses were made for each patient that had not
      been considered. Of the remaining six patients, four (67%) patients with a
      diagnosis of schizophrenia were found to have a diagnosis of affective disorder
      based on the SCID interview (two patients with bipolar disorder, depressed and
      two patients with schizoaffective disorder, depressed). In the remaining two
      (33%) patients, one patient had a diagnosis of mixed dementia due to longstanding
      alcohol abuse with a superimposed primary degenerative dementia of the
      Alzheimer's type. The remaining patient's initial diagnosis of dementia
      associated with alcoholism was changed to bipolar disorder, depressed. These
      results provide support for the hypothesis that older persons with psychiatric
      illness may have been misdiagnosed at a time of less diagnostic rigor.

PMID- 8558620
TI  - The effectiveness of the Masterson curette in sampling the endometrial cavity.
AB  - The Masterson curette was used to sample the endometrial cavity of 25 women prior
      to scheduled hysterectomy for benign or malignant pathology. Adequate amount of
      tissue was obtained in 20 (87%) of 23 patients who did not have endometrial
      atrophy. The Masterson curettage detected all seven cases of endometrial
      hyperplasia or adenocarcinoma for a sensitivity of 100%. However, the Masterson
      curette does not sample the entire endometrial cavity. If abnormal uterine
      bleeding persists despite normal histology on curettings obtained with the
      Masterson or other endometrial sampling device, hysteroscopy is recommended.

PMID- 8558621
TI  - Demographic differences in African-American patients with neoplastic lesions
      detected by flexible sigmoidoscopy.
AB  - There is a higher incidence of colorectal cancer in young African-American
      patients compared with white Americans. This study examines the incidence,
      demographic pattern, and distribution of neoplastic lesions identified by
      flexible sigmoidoscopy in an African-American population. A sample of charts was
      reviewed from an urban gastroenterology practice that serves predominantly
      African Americans. A total of 455 patients were found who underwent flexible
      sigmoidoscopy. The sample included 391 symptomatic patients and 64 asymptomatic
      patients. Two hundred fifty-five patients were < 50 years old and 200 patients
      were > or = 50 years. More neoplastic lesions were found among older patients (21
      patients: 14 with polyps and 7 cancers) than among younger patients (7 patients:
      3 with polyps and 4 cancers); the difference of all positive findings between the
      two groups was significant. However, the cancerous rate for younger patients was
      not statistically different from that for older patients. These findings suggest
      that young African-American patients with colorectal symptoms should undergo
      aggressive approaches to detect cancer early.

PMID- 8558622
TI  - In-utero cocaine exposure and neonatal intestinal perforation: a case report.
AB  - This article describes a case of spontaneous neonatal intestinal perforation in a
      preterm infant with evidence of intrauterine exposure to cocaine. Clinical,
      laboratory, radiological, surgical, and pathological finds were inconsistent with
      necrotizing enterocolitis. Three previous case reports had made the association
      between spontaneous focal neonatal intestinal perforation and prior intrauterine
      cocaine exposure; however, in each case, there were extenuating circumstances
      that may weaken the etiological link. The case described here appears to
      strengthen the association/etiological link. After all other causes of focal
      neonatal intestinal perforation have been excluded, the possibility of
      intrauterine exposure to cocaine should be considered.

PMID- 8558623
TI  - The relationships of anxiety and self-attention to running economy in competitive
      male distance runners.
AB  - Although running economy (RE) is an important physiological characteristic
      associated with superior distance running performance, little is known about the
      potential psychological correlates of RE. Therefore, the current study examined
      the relationship of anxiety and self-attention to RE. Anxiety was measured with
      the Sport Competition Anxiety Test (SCAT; Martens, 1977) and the Trait Anxiety
      Inventory (TAI; Spielberger et al., 1970). Self-attention was assessed with the
      Private Self-Consciousness (PSC) subscale of the Self-Consciousness Scale Revised
      (SCSR; Scheier and Carver, 1985). Running economy was determined by the oxygen
      cost of running at a submaximal velocity of 4.13 m s-1 (< 80% of maximal aerobic
      capacity). The subjects were 18 competitive male distance runners (mean 10-km
      race time 34.17 min). No relationship was found between anxiety (SCAT: r = -0.18,
      N.S.; TAI: r = -0.17, N.S.) and RE. However, PSC and RE were related (r = 0.50, P
      < 0.05), suggesting that runners who habitually directed attention inwards were
      also the most economical. Runners high in PSC may have been more economical
      because they were sensitive to muscle tension interfering with performance and
      subsequently employed relaxation techniques to reduce tension. Additionally, they
      may have employed cognitive techniques aimed at increasing RE such as positive
      self-talk and associative strategies. Despite the tenability of these
      explanations, the association between PSC and RE should be interpreted cautiously
      due to the small sample size.

PMID- 8558624
TI  - Discriminant analysis of biomechanical differences between novice, good and elite
      rowers.
AB  - Oar force and oar angle data resulting from a 6-min maximal rowing ergometer test
      undertaken by novice (n = 9), good (n = 23) and national (n = 9) level male
      rowers, were used to identify biomechanical performance variables which
      accurately discriminated between rowers of differing ability levels. The
      variables included two work capacity measures, mean propulsive power output per
      kilogram of body mass (W kg-1) and propulsive work consistency (%), and two skill
      variables, stroke-to-stroke consistency (%) and stroke smoothness (%).
      Discriminant function analysis indicated the presence of two functions, both of
      which clearly indicated the importance of mean propulsive power output per
      kilogram of body mass as a discriminating variable. Function 2 gave greater
      weight to stroke-to-stroke consistency and stroke smoothness than function 1;
      however, function 1 was the most powerful discriminator. Classification
      procedures were used to predict the ability level to which a rower most likely
      belonged and involved defining the 'distance' between each rower and each ability
      level centroid, with the rower being classified into the 'nearest' ability level.
      These procedures indicated that 100% of the elite, 73.9% of the good, 88.9% of
      the novice and 82.9% of all rowers were correctly classified into their
      respective skill levels. Stepwise discriminant analysis included the variables in
      the following order: mean propulsive power output per kilogram of body mass,
      stroke-to-stroke consistency, stroke smoothness and propulsive work consistency
      (P < 0.001). The results of this study indicate that biomechanical performance
      variables related to rowing capacity and skill may be identified and used to
      discriminate accurately between rowers of differing skill levels, and that, of
      these variables, propulsive work consistency is the least effective
      discriminator.

PMID- 8558625
TI  - The physiological load imposed on basketball players during competition.
AB  - In this study, the intensities of activity and movement patterns during men's
      basketball were investigated by videoing the movements and monitoring the heart
      rate and blood lactate responses of eight elite players during competition. The
      results are expressed according to 'live time', which is actual playing time, and
      'total time', which includes live time as well as all stoppages in play. The mean
      (+/- S.D.) frequency of all activities was 997 +/- 183, with a change in movement
      category every 2.0 s. A mean total of 105 +/- 52 high-intensity runs (mean
      duration 1.7 s) was recorded for each game, resulting in one high-intensity run
      every 21 s during live time. Sixty percent of live time was spent engaged in low
      intensity activity, while 15% was spent in high-intensity activity. The mean
      heart rate (HR) during live time was 169 +/- 9 beats min-1 (89 +/- 2% peak HR
      attained during laboratory testing); 75% of live time was spent with a HR
      response of greater than 85% peak HR. The mean blood lactate concentration was
      6.8 +/- 2.8 mM, indicating the involvement of glycolysis in the energy demands of
      basketball. It is concluded that the physiological requirements of men's
      basketball are high, placing considerable demands on the cardiovascular and
      metabolic capacities of players.

PMID- 8558626
TI  - The effect of sodium bicarbonate ingestion on 1500-m racing time.
AB  - Twelve athletes, all of whom regularly participated in middle- or long-distance
      running races at club to national standard, competed in simulated 1500-m races
      under three conditions: following ingestion of 300 mg sodium bicarbonate per kg
      of body mass (B); following ingestion of a placebo (100 mg sodium chloride per kg
      of body mass and 200 mg calcium carbonate per kg of body mass) (P); and following
      ingestion of neither (C). A double-blind protocol was used between the B and P
      trials. Each condition was replicated so that the athletes competed in six races.
      Ten of the athletes completed all the races. The athletes' average times for
      trials B, P and C were 253.9, 256.8 and 258.0 s, respectively. The data were
      analysed using a two-way ANOVA with replicates and Tukey tests. This revealed a
      difference between trial B and trials P and C (P < 0.05), but no difference
      between trials P and C. These findings, therefore, indicate that sodium
      bicarbonate can have an ergogenic effect upon 1500-m running.

PMID- 8558627
TI  - Running intensity as determined by heart rate is the same in fast and slow
      runners in both the 10- and 21-km races.
AB  - The aims of this study were to determine (1) whether running speed is directly
      proportional to heart rate (HR) during field testing and during 10- and 21-km
      races, and (2) whether running intensity, as estimated from HR measurements,
      differs in 10- and 21-km races and between slow and fast runners at those running
      distances. Male runners were divided into a fast (65-80 min for 21 km; n = 8) or
      slow (85-110 min for 21 km; n = 8) group. They then competed in 10- and 21-km
      races while wearing HR monitors. All subjects also ran in a field test in which
      HR was measured while they ran at predetermined speeds. The 10-km time was
      significantly less in the fast compared with the slow group (33:15 +/- 1:42 vs
      40:07 +/- 3:01 min:s; mean +/- S.D.), as was 21-km time (74:19 +/- 4:30 vs 94:13
      +/- 9:54 min:s) (P < 0.01). Despite the differences in running speed, the average
      running intensity (%HRmax) for the fast and slow groups in the 10-km race was 90
      +/- 1 vs 89 +/- 3% and in the 21-km race 91 +/- 1 vs 89 +/- 2%, respectively. In
      addition, %HRmax was consistently lower in the field test at the comparative
      average running speeds sustained in the 10-km (P < 0.01) and 21-km (P < 0.001)
      races. Hence, factors in addition to work rate or running speed influence the HR
      response during competitive racing. This finding must be considered when running
      intensity for competitive events is prescribed on the basis of field testing
      performed under non-competitive conditions in fast and slow runners.

PMID- 8558628
TI  - Commentary on tumor suppressor gene, distal to BRCA-1, in prostate cancer.

PMID- 8558629
TI  - The influence of diet on urinary stone disease.
AB  - PURPOSE: Conflicting data on the role of diet in the pathogenesis of
      nephrolithiasis prompted us to review the relevant literature regarding the
      impact of diet on urinary stone disease. MATERIALS AND METHODS: MEDLINE searches
      were obtained from 1966 to date using a variety of key words, including
      urolithiasis, nephrolithiasis, diet, protein, carbohydrate, fat, calcium,
      oxalate, phosphate, magnesium, sulfate, citrate, sodium, potassium, fiber,
      fluids, alcohol and vitamins. References earlier than 1966 were obtained through
      bibliographies of these MEDLINE searches. The search included in vitro and in
      vivo animal and human studies. RESULTS: Of the extracted articles 83% addressed
      the issue of nephrolithiasis and diet, and were included in this report. All
      articles were independently reviewed by each of us. The reviews were summarized
      and compiled according to each dietary component. CONCLUSIONS: Appropriate
      dietary manipulation may be beneficial in the prevention of recurrent
      urolithiasis in only a select group of patients.

PMID- 8558630
TI  - Histological characteristics of radical prostatectomy specimens in men with a
      serum prostate specific antigen of 4 ng./ml or less.
AB  - PURPOSE: Of most reported radical prostatectomy series 20% consist of men with a
      serum prostate specific antigen (PSA) of 4.0 ng./ml. or less. Since our series is
      not only prospective but all prostates are reconstructed at 3 mm. intervals, we
      determined the clinical and histological findings in this important subset of men
      undergoing radical prostatectomy. MATERIALS AND METHODS: Of 911 consecutive men
      undergoing radical prostatectomy 187 (21%) had a preoperative serum PSA of 4.0
      ng./ml. or less (values equivalent to those of the Hybritech Tandem-R assay).
      RESULTS: Mean tumor volume was 2.3 cc. Of the 187 cancers 156 (83%) were in the
      peripheral zone and 31 (17%) in the transition zone, while 137 (73%) were organ
      confined and 50 (27%) showed capsular penetration. No patient had positive pelvic
      lymph nodes, only 5 had seminal vesicle invasion and positive surgical margins
      were present in 14%. Cancer volumes less than 0.5 cc were noted in 9% of the
      patients and were probably insignificant. At an average followup of 37 months,
      only 16 men (9%) had a detectable serum PSA. These 16 patients had a larger tumor
      volume (3.7 cc versus 2.2 cc, p < 0.05), and a greater percent of Gleason grade 4
      and/or 5 disease than the 171 with undetectable PSA. CONCLUSIONS: Men with
      prostate cancer and a serum PSA of 4.0 ng./ml. or less are excellent candidates
      for radical prostatectomy if the 9% with clinically insignificant tumors can be
      avoided. Since 70% of all men had a suspicious prostate on digital rectal
      examination, this evaluation is important for men with a serum PSA of 4.0 ng./ml.
      or less.

PMID- 8558631
TI  - Long-term followup of patients with tumor thrombi from renal cell carcinoma and
      total replacement of the inferior vena cava using an expanded
      polytetrafluoroethylene tubular graft.
AB  - PURPOSE: Inferior vena caval resection and its reconstruction are sometimes
      necessary when the inferior vena cava is extensively involved by a large and
      fixed tumor thrombus from renal cell carcinoma or other malignancies. We
      successfully replaced the inferior vena cava using tubular expanded
      polytetrafluoroethylene (Teflon) vascular grafts after en bloc removal of the
      tumor thrombus and inferior vena cava. We followed the patients long term and
      observed inferior vena caval patency. MATERIALS AND METHODS: The 3 men and 2
      women ranged from 42 to 75 years old. The renal tumors were on the right side in
      4 patients and asynchronously bilateral in 1. The suprarenal inferior vena cava
      was replaced in 3 patients and the infrarenal portion was replaced in 2. The
      expanded polytetrafluoroethylene tube grafts, 18 to 22 mm. in diameter and 5 to
      12 cm. long, were externally stented in 3 patients and not stented in 2. RESULTS:
      Followup ranged from 6 to 96 months (mean 58). Long-term patency of the graft was
      maintained in all patients. Of the patients 3 had no evidence of disease at 6
      months and 2 died of recurrent tumor at 6 and 84 months. CONCLUSIONS: Total
      replacement of the inferior vena cava using an expanded polytetrafluoroethylene
      tubular graft may offer a feasible method with good patency rates in the long
      term.

PMID- 8558632
TI  - Long-term followup after surgical treatment for renal cell carcinoma extending
      into the right atrium.
AB  - PURPOSE: Renal cell carcinoma extends into the inferior vena cava in 4 to 10% of
      patients and it is believed that the cephalad extent of inferior vena caval
      involvement is inversely correlated with survival. We evaluated this issue
      further. MATERIALS AND METHODS: From June 1984 to August 1993, 18 patients
      underwent surgical treatment for localized renal cell carcinoma and an inferior
      vena caval thrombus extending into the right atrium. One patient had a
      contralateral adrenal metastasis at operation. All patients underwent complete
      tumor excision with radical nephrectomy and inferior vena caval thrombectomy
      using adjunctive cardiopulmonary bypass and deep hypothermic circulatory arrest.
      Pathological study indicated no renal capsular penetration of renal cell
      carcinoma in 10 patients and perinephric fat involvement in 8. RESULTS: The
      overall and cancer-specific 5-year survival rates were 56.6% and 60.2%,
      respectively. Eight patients (45%) were free of malignancy at a mean of 71.6
      months. One patient was alive with metastatic disease 15 months postoperatively.
      There was 1 operative death, while 8 patients died of metastatic renal cell
      carcinoma at a mean of 18.8 months postoperatively. Mean postoperative survival
      was significantly improved in patients with no renal capsular penetration by
      tumor compared to those with perinephric fat involvement (58.1 versus 19.7
      months, p = 0.035). CONCLUSIONS: Long-term survival after surgical treatment is
      possible in patients with localized renal cell carcinoma extending into the right
      atrium. In patients with localized renal cell carcinoma and an inferior vena
      caval tumor thrombus the cephalad extent of inferior vena caval involvement does
      not appear to be prognostically important.

PMID- 8558633
TI  - Predictive value of magnetic resonance imaging and computerized tomography for
      conservative renal surgery in an ex vivo tumor enucleation study followed by step
      sectioning.
AB  - PURPOSE: Due to the early diagnosis of many renal cell cancers, the treatment
      options of organ conserving surgery is of interest even for patients with a
      normal contralateral kidney. To our knowledge the predictive value of
      preoperative investigations in such patients has not been clarified. MATERIALS
      AND METHODS: In a prospective study of 30 patients with stage T1/T2 renal cell
      carcinoma ex vivo enucleation was performed following tumor nephrectomy. Magnetic
      resonance imaging (MRI) and computerized tomography (CT) were done preoperatively
      in all patients. For pathological evaluation the kidneys were step-sectioned in 1
      mm. slices. Macroscopic and microscopic findings were compared to those of the
      preoperative investigations. RESULTS: Mean tumor diameter was 4.6 cm. (range 2.0
      to 10.0). Twelve tumors were incidental and smaller than 4 cm. Residual carcinoma
      due to incomplete resection was found in 4 kidneys with tumors larger than 4 cm.
      Parenchymal or hilar venous invasion was noted in 4 cases, including 1 in the
      incidental group. Prediction of renal fat capsule invasion by MRI was highly
      confirmed by pathological examination. On the other hand, parenchymal venous
      involvement or secondary renal tumors smaller than 2 cm. could not be predicted
      by MRI or CT. CONCLUSIONS: Neither MRI nor CT predicts complete tumor control
      when conservative renal surgery is considered. All incidental tumors smaller than
      4 cm. could be resected completely by nephron sparing surgery. Nevertheless,
      microscopic venous invasion was present in 1 of the latter cases.

PMID- 8558634
TI  - Phase II study of interferon-gamma versus interleukin-2 and interferon-alpha 2b
      in metastatic renal cell carcinoma.
AB  - PURPOSE: In a randomized phase II study we evaluated response, survival and side
      effects of low dose recombinant interferon-gamma in 30 patients (group 1) versus
      recombinant interleukin-2 and interferon-alpha 2b in 30 (group 2) with metastatic
      renal cell carcinoma. MATERIALS AND METHODS: Group 1 received 200 micrograms
      interferon-gamma subcutaneously once a week. Group 2 received 4 x 4.8 x 10(6)
      IU/m.2 interleukin-2 subcutaneously on days 1 and 22, 2 x 4.8 x 10(6) IU/m.2 on
      days 2 and 23, and 2 x 2.4 x 10(6) IU/m.2 combined with interferon-alpha 2b
      subcutaneously at 3 x 10(6) IU/m.2 on days 3, 5, 24 and 26, and 6 x 10(6) IU/m.2
      3 times weekly for 6 weeks. RESULTS: Toxicity grades 2 and 3 (World Health
      Organization) were observed in group 2 only. After followup of 13 months there
      was no remission in group 1 compared to 7 remissions in group 2, with 23 cases of
      progressive disease detected. CONCLUSIONS: Combination therapy showed an
      objective response rate of 23% (p = 0.01). Although survival was not a primary
      aim of the study, there was a tendency toward no significant difference in
      survival when evaluating these relatively small groups (p = 0.49).

PMID- 8558635
TI  - Value of deoxyribonucleic acid ploidy and nuclear morphometry for prediction of
      disease progression in renal cell carcinoma.
AB  - PURPOSE: A retrospective study was performed on 108 patients with localized renal
      cell carcinoma (pT1 to 3a N0M0) to determine whether ploidy and nuclear
      morphometry are independent predictive factors in addition to stage and grade.
      MATERIALS AND METHODS: Deoxyribonucleic acid (DNA) content was analyzed by flow
      cytometry and nuclear morphometry characterized by 5 nuclear descriptors. A Cox
      proportional hazards regression model was used to identify significant prognostic
      factors for disease progression. RESULTS: A model combining tumor stage and
      grade, DNA ploidy and nuclear minor axis was chosen as optimal with risk of
      disease progression increased with increasing tumor stage and grade, DNA
      aneuploidy and increasing nuclear minor axis. CONCLUSIONS: This improved ability
      to predict disease progression in localized renal cell carcinoma may have
      important clinical use.

PMID- 8558636
TI  - Kidney cancer.

PMID- 8558637
TI  - Elevated levels of basic fibroblast growth factor in the urine of clam
      enterocystoplasty patients.
AB  - PURPOSE: We determined whether basic fibroblast growth factor is elevated in the
      urine of patients who have undergone clam ileocystoplasty. MATERIALS AND METHODS:
      An immunoassay technique was used to measure urinary basic fibroblast growth
      factor in 50 patients equally divided between those with and without neuropathy
      who had undergone clam enterocystoplasty. The results were compared with urinary
      basic fibroblast growth factor concentrations from 25 healthy age and sex matched
      volunteers. RESULTS: There is a highly significant elevation of urinary basic
      fibroblast growth factor in clam enterocystoplasty patients compared to controls,
      which is not related to the presence or absence of infection. There is no
      difference between those with and without neuropathy. CONCLUSIONS: Elevated
      levels of basic fibroblast growth factor are an important consideration in the
      malignant potential of the clam procedure.

PMID- 8558638
TI  - Do human papillomaviruses have a role in the pathogenesis of bladder carcinoma?
AB  - PURPOSE: Since little is known of the associations between bladder carcinoma and
      human papillomaviruses (HPVs), data on the role of HPV in bladder carcinogenesis
      are controversial. We attempted to clarify whether HPVs are present in bladder
      carcinomas. MATERIALS AND METHODS: We examined 36 specimens of bladder carcinoma
      for HPV positivity by the polymerase chain reaction method. RESULTS: HPV-16
      deoxyribonucleic acid was detected in 1 specimen (3%) of a transitional cell
      carcinoma from a 37-year-old woman who had concomitant squamous cell carcinoma of
      the uterine cervix with positive para-aortic lymph node metastasis. The cervical
      tumor, bladder tumor and para-aortic lymph node metastasis were all positive for
      the same type of HPV. CONCLUSIONS: On the basis of this low rate of HPV detection
      (3%), HPVs are not likely to have a prominent role in carcinogenesis of the
      bladder.

PMID- 8558639
TI  - Initial evaluation of the bladder tumor antigen test in superficial bladder
      cancer.
AB  - PURPOSE: We analyzed the value of the Bard bladder tumor antigen (BTA*) test for
      the diagnosis of stage Ta superficial bladder cancer and carcinoma in situ, and
      compared it to the highly sensitive bladder washing cytology. MATERIALS AND
      METHODS: The BTA test is a latex agglutination test that qualitatively detects
      the presence of basement membrane complexes in the urine. A total of 60 patients
      with superficial bladder cancer underwent voided urine BTA analysis and bladder
      washing cytologies. RESULTS: Of the patients 65% were correctly diagnosed with
      the BTA test compared to 32% with bladder washings, which is statistically
      significant (p < 0.001). CONCLUSIONS: The BTA test is a noninvasive diagnostic
      tool that is superior to bladder washing cytology for diagnosing superficial
      bladder cancer.

PMID- 8558640
TI  - Urinary cytokines during intravesical bacillus Calmette-Guerin therapy for
      superficial bladder cancer: processing, stability and prognostic value.
AB  - PURPOSE: An accurate prognostic indicator to identify nonresponding patients with
      superficial transitional cell carcinoma of the bladder at an early stage of
      intravesical bacillus Calmette-Guerin (BCG) therapy is urgently needed. MATERIALS
      AND METHODS: The processing conditions and stability of several BCG induced
      urinary cytokines were analyzed, as was the possible correlation between these
      cytokines (indicating immune responsiveness to BCG) and bladder tumor recurrence.
      We studied 23 patients with superficial transitional cell carcinoma of the
      bladder. Monitoring was performed by serial collection of urine during the first
      24 hours after each of the 6 consecutive weekly intravesical BCG instillations.
      Baseline pre-therapy cytokine levels were 3.9 +/- 4.7 pg./mumol creatinine for
      interleukin-6 and 0.1 +/- 0.2 pg./mumol creatinine for tumor necrosis factor
      alpha (all measured by enzyme-linked immunosorbent assay). To investigate the
      correlation between interleukin-2 and bladder tumor recurrence, patients were
      stratified into 2 groups based on an early (6 months or less) or late (greater
      than 6 months) recurrent tumor. For each patient the highest cytokine value
      measured during the 6-week BCG treatment course was evaluated. RESULTS: The
      results were positive if the level in urine exceeded 0.34 units interleukin-2 per
      mumol. creatinine. A significant correlation between urinary interleukin-2 and
      tumor recurrence was found (p = 0.003, 23 patients). Of the studied cytokines
      obtained from BCG treated patients, interleukin-1 beta, 2 and 6 but not tumor
      necrosis factor-alpha were stable in urine at 4C and 20C. At 37C all cytokines
      were unstable. Interferon-gamma could only be detected in immediately dialyzed
      urine and its occurrence correlated most with that of interleukin-2. Processing
      of urine by centrifugation to remove leukocytes immediately after collection was
      not required for reliable measurements of interleukins-2 and 6. Based on these
      results interleukins-2 and 6 were preferred for extensive monitoring of the BCG
      induced immune reaction. CONCLUSIONS: Our study provides significant evidence for
      a correlation between urinary cytokine induction and clinical response following
      intravesical BCG therapy. Particularly, monitoring of interleukin-2 may have the
      potential for prognostic value provided that strict precautions regarding urine
      collection, such as maximal 2-hour sampling and immediate cooling, are taken.

PMID- 8558642
TI  - Superficial bladder cancer--incremental insight.

PMID- 8558641
TI  - Intravesical versus intravesical plus intradermal bacillus Calmette-Guerin: a
      prospective randomized study in patients with recurrent superficial bladder
      tumors.
AB  - PURPOSE: Intravesical instillation of bacillus Calmette-Guerin (BCG) induces
      various immunological reactions and decreases the recurrence rate of superficial
      bladder tumors. To determine whether additional immune stimulation with
      concomitant intradermal BCG applications could further lower the recurrence rate,
      154 patients with superficial bladder tumors at high risk for recurrence were
      randomized to receive either 6 intravesical instillations of 120 mg. Pasteur
      strain BCG alone or combined with intradermal application. MATERIALS AND METHODS:
      A total of 76 patients received intravesical and intradermal BCG, while 78
      received intravesical BCG only. Median followup was 41 months (range 2 to 89) and
      36 months (range 2 to 86), respectively. Both treatment groups were comparable
      regarding patient age and number of previous transurethral bladder tumor
      resections, as well as tumor recurrence rate, stage and grade before BCG therapy.
      RESULTS: A highly significant decrease in the monthly tumor recurrence rate was
      observed in both arms after BCG compared to the pretreatment recurrence rates (p
      < 0.0001). Recurrence rate decreased from 0.73 +/- 1.07 (standard deviation) to
      0.06 +/- 0.13 in the combined treatment group and from 0.71 +/- 0.90 to 0.074 +/-
      0.17 in the intravesical treatment only group. However, we were unable to find
      any difference between the 2 groups regarding interval to initial recurrence or
      recurrence rates after BCG treatment. Changes in the purified protein derivative
      skin test performed before and after BCG therapy were not useful to predict
      response to treatment because 44% of our patients already had a positive test
      before treatment. Also, interpretation of the skin test was difficult and not
      always reliable. In the multivariate analysis, however, fever was an important
      prognostic factor. Patients with increased body temperature greater than 37.5C
      had a significantly lower recurrence rate than those without fever (37.5C or
      less) after BCG instillation (p = 0.009). Moreover, fever after BCG instillation
      was observed significantly more frequently in patients with a positive purified
      protein derivative skin test before treatment (p = 0.021). CONCLUSIONS: The
      therapeutic benefit from intravesical BCG apparently was not substantially
      improved by simultaneous intradermal BCG vaccination. Fever following
      intravesical BCG instillation is an important prognostic factor regarding
      superficial bladder tumor recurrence. Fever occurs predominantly in patients who
      were previously sensitized to mycobacteria (by BCG vaccination or infection) as
      shown by a positive pretreatment purified protein derivative skin test. This
      finding suggests that previously sensitized patients respond significantly better
      to a single course of intravesical BCG.

PMID- 8558643
TI  - Local recurrence and survival following nerve sparing radical cystoprostatectomy
      for bladder cancer: 10-year followup.
AB  - PURPOSE: The efficacy of nerve sparing radical cystoprostatectomy for the
      treatment of bladder cancer has been evaluated. We reviewed our 10-year
      experience with this technique to ascertain survival and local recurrence rates.
      MATERIALS AND METHODS: The charts of 101 patients treated with nerve sparing
      cystoprostatectomy between March 1982 and November 1989 were reviewed and
      updated. RESULTS: The disease-specific 10-year survival rate for all stages of
      bladder cancer treated was 69% and the 10-year survival rate free of local
      recurrence was 94%. Recovery of sexual function following nerve sparing
      cystectomy correlated with patient age: 62% in men 40 to 49 years old, 47% in men
      50 to 59 years old, 43% in men 60 to 69 years old and 20% in men 70 to 79 years
      old. CONCLUSIONS: Nerve sparing radical cystoprostatectomy does not compromise
      cancer control and provides improved postoperative quality of life.

PMID- 8558644
TI  - A randomized trial of radical cystectomy versus radical cystectomy plus
      cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder
      cancer.
AB  - PURPOSE: Standard treatment for muscle invasive transitional cell cancer of the
      bladder is radical cystectomy. Despite careful staging, the majority of cancers
      with regional lymph node involvement and/or invasion to adjacent organs
      eventually recur. We investigated the benefit of chemotherapy with cisplatin,
      methotrexate and vinblastine (CMV) after radical cystectomy. MATERIALS AND
      METHODS: A prospective trial was done in which patients were randomized after
      cystectomy to receive either 4 cycles of CMV chemotherapy or observation. At
      relapse, patients were treated with standard CMV chemotherapy for metastatic
      disease at our institution. RESULTS: Of 55 patients who entered this trial 1 was
      ineligible and in 4 it is too soon to be evaluated. Of the 50 evaluable patients
      25 were randomized to receive adjuvant CMV chemotherapy and 25 were observed. In
      the CMV arm 12 (48%) and in the observation arm 5 (25%) never had recurrence.
      With a median followup of 62 months and no patient with less than 2 years of
      followup, the freedom from progression in the adjuvant chemotherapy group was
      superior to that in the observation group (median 37 versus 12 months,
      respectively, p = 0.01). Median survival in the adjuvant group was 63 months
      compared to 36 months for the observation group. Surprisingly, some cases with
      relapse could be salvaged with CMV chemotherapy, perhaps contributing to this
      lack of difference in overall survival (p = 0.32). CONCLUSIONS: Treatment with
      CMV chemotherapy after radical cystectomy is an acceptable approach in patients
      with stages p3b and p4N0 or N1 transitional cell carcinoma of the bladder.
      Further studies must be performed to determine whether these results can be
      extrapolated to patients with more limited disease (stages p2 and p3a) who are
      currently treated with radical cystectomy or definitive irradiation.

PMID- 8558645
TI  - The risk of upper tract recurrence following cystectomy in patients with
      transitional cell carcinoma involving the distal ureter.
AB  - PURPOSE: Risk factors for the development of an upper urinary tract transitional
      cell carcinoma following radical cystectomy are identified. MATERIALS AND
      METHODS: The records of 430 patients who underwent cystectomy for transitional
      cell carcinoma of the bladder between 1981 and 1988 were retrospectively
      reviewed. RESULTS: Upper tract tumors developed in 11 patients (2.6%) at a median
      of 40 months after radical cystectomy. Of the potential risk factors evaluated
      only the presence of transitional cell carcinoma within the distal ureter showed
      a statistically significant correlation with upper tract recurrence (p = 0.001).
      Six of the 11 recurrent neoplasms were asymptomatic. Among the patients with
      upper urinary tract recurrence 5 died of disease, 4 had no evidence of disease
      and 2 were alive with cancer. CONCLUSIONS: Patients with distal ureteral
      involvement at cystectomy are at a high risk for upper tract recurrence. These
      patients should be monitored with routine upper tract cytology and imaging
      studies.

PMID- 8558646
TI  - Radical cystectomy--cornerstone or millstone?

PMID- 8558647
TI  - Conventional urodynamics and ambulatory monitoring in the definition and
      management of bladder outflow obstruction.
AB  - PURPOSE: We determined whether ambulatory urodynamics and new objective methods
      of defining bladder outflow obstruction might improve the classification of
      bladder outflow obstruction over conventional urodynamics (cystometrography), and
      whether such measures might improve prediction of the outcome of prostatectomy.
      MATERIALS AND METHODS: A prospective study was performed of 122 men undergoing
      prostatectomy for symptoms and low flow rates. Cystometrography and ambulatory
      urodynamics were performed before and 6 months after prostatectomy but did not
      influence selection for operation. Methods of classifying obstruction included
      the Abrams-Griffiths nomogram, Schafer linear passive urethral resistance
      relation and Griffiths urethral resistance factor. RESULTS: The proportion of
      cases defined as obstructed did not differ on ambulatory urodynamics or
      cystometrography or when the Abrams-Griffiths nomogram was compared to the linear
      passive urethral resistance relation or urethral resistance factor. Significant
      improvements after prostatectomy were noted in flow rates (p < 0.001), residual
      urine (p < 0.001), voiding pressure (p < 0.001) and symptom scores (p < 0.001).
      Ambulatory urodynamics were more sensitive than cystometrography in detection of
      detrusor instability but detrusor instability did not correlate with outcome.
      Voiding pressures were greater during ambulatory urodynamics (p < 0.02). The
      outcome of obstructed cases (on Abrams-Griffiths nomogram during ambulatory
      urodynamics) was better (79% good outcome) than that of nonobstructed or
      equivocally obstructed cases (55% good symptomatic outcome, p < 0.05).
      CONCLUSIONS: Men proved to have obstruction on the basis of pressure and flow
      measurements applied to a nomogram have better outcomes after transurethral
      resection of the prostate but sophisticated or computer derived methods of
      classification of obstruction did not improve prediction.

PMID- 8558648
TI  - Endoscopic collagen injection therapy in elderly women with type I stress urinary
      incontinence.
AB  - PURPOSE: The safety and efficacy of collagen injection therapy for the treatment
      of type I stress urinary incontinence were determined. MATERIALS AND METHODS: A
      total of 12 women 68 to 85 years old (mean age 76) with type I stress urinary
      incontinence underwent collagen injection. Incontinence was subjectively
      categorized as grades 0 to 3, and Valsalva leak point pressures were measured
      before and after injection. RESULTS: At a mean of 10.3 months (range 3 to 24) 10
      of the 12 women (83%) were cured, while the remaining 2 noticed subjective
      improvement in incontinence. Average number of injections per patient was 1.25 (1
      injection in 9 and 2 in 3), average total collagen injected per patient was 2.2
      cc (range 1.0 to 3.5) and average increase in Valsalva leak point pressure after
      collagen injection was 22 cm. water (range 0 to 40). CONCLUSIONS: Collagen
      injection appears to be an effective alternative method for the treatment of type
      I stress urinary incontinence in elderly women.

PMID- 8558649
TI  - Laparoscopic Burch bladder neck suspension: early results.
AB  - PURPOSE: The Burch suspension is an effective treatment for stress urinary
      incontinence due to hypermobility. To decrease the associated morbidity and
      hospital stay, we attempted the procedure laparoscopically in 46 women. MATERIALS
      AND METHODS: All patients had stress incontinence with bladder neck
      hypermobility. Preoperative testing included cystoscopy, multichannel urodynamics
      with pressure-flow studies and measurement of Valsalva leak point pressure. Mean
      patient age was 49.5 years (range 26 to 70). RESULTS: In 12 patients the
      laparoscopic approach could not be completed and an open operation was performed.
      Of the 34 laparoscopic Burch procedures 13 were performed transperitoneally and
      21 extraperitoneally. Mean operative time was 196 minutes (range 130 to 300),
      mean blood loss 96.3 cc (range 50 to 400) and mean postoperative hospital stay
      3.2 days (range 1 to 8). Five postoperative complications included
      hematoma/anemia in 2 patients, transient urinary retention in 1, enterocele in 1
      and uterine prolapse in 1. Mean followup was 17.3 months (range 12 to 26). Of the
      34 patients only 5 had persistent incontinence postoperatively (3 with stress and
      urge incontinence, 1 with stress incontinence only and 1 with urge incontinence
      only). Overall, 85% of the patients are totally dry. With experience the
      operative time and postoperative stay decreased. The extraperitoneal and
      transperitoneal approaches provide certain advantages. CONCLUSIONS: The Burch
      suspension performed laparoscopically appears to have a favorable morbidity
      profile with a successful continence outcome. However, there is a steep learning
      curve to the procedure as manifested by the long operative time.

PMID- 8558650
TI  - Silent autonomic dysreflexia during voiding in men with spinal cord injuries.
AB  - PURPOSE: We determined whether symptoms of autonomic dysreflexia correlated with
      elevations in blood pressure in men with spinal cord injuries. MATERIALS AND
      METHODS: During a routine yearly urodynamic evaluation 45 consecutive men with
      complete spinal cord injuries above T6 underwent simultaneous monitoring of blood
      pressure and symptoms of autonomic dysreflexia. Those with systolic blood
      pressure of greater than 160 mm. Hg or diastolic blood pressure of greater than
      90 mm. Hg during voiding were assigned to the hypertensive group. During voiding
      35 men (78%) had significant hypertension. RESULTS: Before voiding there was no
      statistical difference in mean systolic blood pressure between men with and
      without hypertension (117 versus 110 mm. Hg, p = 0.28). During uninhibited
      contractions and voiding mean systolic blood pressure of the normotensive group
      (131 mm. Hg) versus the hypertensive group (169 mm. Hg) was statistically
      significant (p < 0.0001). Of the 35 hypertensive patients 15 (43%) had no
      symptoms of autonomic dysreflexia. There was no correlation of autonomic
      dysreflexia with length of injury, maximum voiding pressure or bladder capacity
      (p = 0.59, 0.85 and 0.34, respectively). CONCLUSIONS: Urodynamics are helpful to
      detect symptomatic and asymptomatic autonomic dysreflexia. Significant elevations
      in blood pressure can occur without the symptoms of autonomic dysreflexia.

PMID- 8558651
TI  - Voiding dysfunction in human immunodeficiency virus infections.
AB  - PURPOSE: We prospectively evaluated the current spectrum of urodynamic pathology
      in patients infected with human immunodeficiency virus (HIV) who presented with
      voiding dysfunction. MATERIALS AND METHODS: We obtained a directed genitourinary
      and neurological history, and performed a physical examination and urodynamic
      testing in 18 patients. A 4-channel membrane urethral catheter was used to record
      intravesical and intraurethral pressures simultaneously. RESULTS: Detrusor
      hyperreflexia was present in 28% of our patients and detrusor-sphincter
      dyssynergia in 28%. Detrusor areflexia, previously described as the most frequent
      abnormality, was uncommon in our series (6% of patients). CONCLUSIONS: This
      changing proportion of urodynamic diagnoses may reflect a changing pattern of
      neurological manifestations of HIV infection due to more aggressive management.
      Urodynamic evaluation remains critical for precise diagnosis and treatment in
      patients with HIV who present with urinary symptoms.

PMID- 8558652
TI  - The impact of technological and scientific advances in understanding, evaluating
      and managing bladder and outlet obstruction.

PMID- 8558653
TI  - Prevalence of hypothalamic-pituitary imaging abnormalities in impotent men with
      secondary hypogonadism.
AB  - PURPOSE: Because prevalence of structural lesions of the pituitary and
      hypothalamus in impotent men with secondary hypogonadism was undefined, we
      evaluated 164 men 27 to 79 years old whose chief complaint was erectile
      dysfunction and who repeatedly had low serum testosterone levels (less than 230
      ng./dl.). MATERIALS AND METHODS: With computerized tomography or magnetic
      resonance imaging of the sella we detected potentially serious lesions (pituitary
      lesions greater than 5 mm. or any hypothalamic lesion) in 11 men (6.7%, 95%
      confidence interval 2.9 to 10.5%), including 5 pituitary microadenomas (5 mm. or
      larger), 4 pituitary macroadenomas and 2 hypothalamic lesions. RESULTS: Mean
      serum testosterone was lower in patients with (121 +/- 66 ng./dl., standard
      deviation) than without (177 +/- 39 ng./dl.) hypothalamic or pituitary imaging
      abnormalities (p < 0.001). For every 10 ng./dl. decrease in testosterone the risk
      of hypothalamic or pituitary imaging abnormalities increased 1.2-fold (p <
      0.005). Macroadenomas and hypothalamic lesions were confined to 6 subjects with
      testosterone levels of 104 ng./dl. or less. CONCLUSIONS: The risk of hypothalamic
      or pituitary imaging abnormalities is low among men evaluated for erectile
      dysfunction and secondary hypogonadism. However, this risk increases markedly
      when the serum testosterone level is markedly decreased.

PMID- 8558654
TI  - Vacuum erection associated impotence and Peyronie's disease.
AB  - PURPOSE: Use of a nonmedical, catalogue type vacuum erection device resulted in a
      case of vacuum induced vasculogenic impotence and Peyronie's disease. MATERIALS
      AND METHODS: A 66-year-old potent man used a nonmedical vacuum erection device
      (cylinder plus a hand pump without a pressure-release valve and a doughnut-shaped
      ring at the base without tension bands) after having achieved a spontaneous rigid
      erection. The resultant excessive overinflation of the penis was followed by
      dorsal curvature, diminished rigidity and decreased erectile maintenance.
      RESULTS: Physical examination revealed a dorsal mid shaft Peyronie's plaque.
      Nocturnal penile tumescence testing and office injection testing were abnormal
      and demonstrated partial, short-lived, dorsally curved erections. Dynamic
      pharmaco-cavernosometry and pharmaco-cavernosography established vasculogenic
      impotence with site-specific crural (unrelated to the Peyronie's plaque) veno
      occlusive dysfunction and dorsal penile curvature. CONCLUSIONS: Vacuum erection
      devices create pulling forces on the penis. We estimate that the pulling forces
      in this case were prohibitively high (approximately 29 pounds) due to absence of
      a pressure-release valve and to the preexistent erection at vacuum application.
      These intense pulling forces are hypothesized to have damaged the tunica in the
      mid shaft (Peyronie's disease) and the crus (veno-occlusive dysfunction), the
      latter being the site of attachment of the corpora to the ischiopubic ramus and a
      most likely location for high magnitude pulling forces to exert an abnormal
      injury effect. The patient underwent a Nesbit plication procedure and presently
      performs self-injection for satisfactory sexual activity.

PMID- 8558655
TI  - The effect of intracorporeal injection plus genital and audiovisual sexual
      stimulation versus second injection on penile color Doppler sonography
      parameters.
AB  - PURPOSE: We assessed whether genital and audiovisual sexual stimulation following
      1 or 2 intracorporeal injections caused the greatest changes in penile
      hemodynamics as recorded by color Doppler sonography. MATERIALS AND METHODS: A
      total of 50 impotent patients underwent multiphasic color Doppler sonography of
      the cavernous arteries before and after intracorporeal injection (phase 1),
      subsequent genital and audiovisual sexual stimulation (phase 2), a second
      injection (phase 3) and repeat genital and audiovisual sexual stimulation (phase
      4). Peak systolic velocity, end diastolic velocity, resistance index and erectile
      response were studied. RESULTS: Penile erection after injection 1 was upgraded in
      41 patients (82%) by genital and audiovisual sexual stimulation. Further
      upgrading due to injection 2 with stimulation was noted in 11 patients (22%).
      Among the patients who completed the 4 phases of the test the maximal peak
      systolic velocity was noted after 1 and 2 injections in 20 (59%) and 14 (41%),
      respectively. The resistive index was always increased by genital and audiovisual
      sexual stimulation compared to post-injection values. The maximal resistive index
      occurred after initial and repeat genital and audiovisual sexual stimulation in
      15 (48%) and 16 (52%) patients, respectively. After injection 1 with genital and
      audiovisual sexual stimulation, impotence was diagnosed as nonvasculogenic in 14
      patients (28%), arteriogenic in 9 (18%), venogenic in 17 (34%) or mixed
      arteriovenogenic in 10 (20%). After injection 2 with stimulation these results
      were noted in 18 (36%), 9 (18%), 13 (26%) and 10 (20%) patients, respectively.
      Thus, there were 4 false-positive cases (8%) of venogenic impotence. CONCLUSIONS:
      To study cavernous artery inflow and veno-occlusive function, color Doppler
      sonography should be performed after injection plus genital and audiovisual
      sexual stimulation. When the erectile response does not equal the maximal
      physiological erection reported by the patient, a second injection with
      stimulation should be given.

PMID- 8558657
TI  - Impotence.

PMID- 8558656
TI  - Evolving concepts in the diagnosis and treatment of arterial high flow priapism.
AB  - PURPOSE: We investigated 2 evolving concepts in the management of arterial
      priapism: 1) the efficacy of perineal duplex Doppler ultrasound as a diagnostic
      alternative to arteriography and 2) the therapeutic alternative of expectant
      management. MATERIALS AND METHODS: We evaluated 10 patients with high flow
      arterial priapism. RESULTS: Compared to selective internal pudendal
      arteriography, perineal duplex Doppler ultrasonography was associated with 100%
      sensitivity and 73% specificity rates. Compared to physical examination, followup
      duplex ultrasonography had a sensitivity of 75% and specificity of 100%. Followup
      penile duplex ultrasound demonstrated restoration of antegrade flow in the
      cavernous artery after embolization. Patients on expectant management remained
      potent as long as 31 years. CONCLUSIONS: Diagnostic perineal duplex Doppler
      ultrasonography and expectant management are valuable tools for the treatment of
      arterial priapism. A new algorithm for patient care is presented.

PMID- 8558658
TI  - Penetrating trauma to the penis: functional results.
AB  - PURPOSE: The erectile function, cosmetic appearance, indications for surgical
      exploration and need for specific diagnostic tests were evaluated in patients
      with penetrating penile trauma. MATERIALS AND METHODS: We reviewed 26 cases of
      penetrating penile trauma seen during a 4-year period. RESULTS: All patients with
      corporeal injuries who were followed (73%) were potent. Two patients with minimal
      corporeal injury who did not undergo exploration did well. Retrograde
      urethrography did not identify any previously unsuspected urethral injuries.
      CONCLUSIONS: Excellent functional results may be obtained after penetrating
      trauma to the penis. Select patients may not require retrograde urethrography and
      some with minimal wounds, even if involving the corpora, can be treated
      nonoperatively.

PMID- 8558659
TI  - Vibratory stimulation and rectal probe electroejaculation as therapy for patients
      with spinal cord injury: semen parameters and pregnancy rates.
AB  - PURPOSE: The conception rate of patients with spinal cord injuries following
      penile vibratory stimulation and rectal probe electroejaculation in conjunction
      with self-insemination, intrauterine insemination or assisted reproductive
      technique is poorly documented. We reviewed our success rates with penile
      vibratory stimulation and rectal probe electroejaculation, and the pregnancy
      rates achieved with self-insemination, intrauterine insemination and assisted
      reproductive techniques. MATERIALS AND METHODS: A total of 78 consecutive
      patients with spinal cord injuries had a complete neurological examination and
      was treated initially with penile vibratory stimulation. If unsuccessful, rectal
      probe electroejaculation was performed to obtain an ejaculate. The ejaculate was
      then used with self-insemination, intrauterine insemination or assisted
      reproductive techniques and pregnancies were monitored. RESULTS: Vibratory
      stimulation was successful in 20 of 37 patients (54%) with a cervical lesion, 14
      of 26 (54%) with a lesion at or above T10 and none of 15 when the lesion was
      below T10. All patients except 2 who elected followup rectal probe
      electroejaculation had antegrade or retrograde ejaculate. Six patients (7.7%)
      with extremely poor semen quality were not candidates for assisted fertilization.
      Of 27 couples who attempted conception 17 were successful (5 self-insemination, 5
      intrauterine insemination and 7 assisted reproductive techniques). CONCLUSIONS:
      Penile vibratory stimulation should be used as first line therapy in patients
      with lesions above T10 while rectal probe electroejaculation should be considered
      as a second option. Motivated patients can achieve success with self
      insemination, intrauterine insemination and assisted reproductive techniques.

PMID- 8558660
TI  - Accurate staging of carcinoma of the penis in men with nonpalpable inguinal lymph
      nodes by modified inguinal lymphadenectomy.
AB  - PURPOSE: The accuracy and safety of a modified inguinal lymphadenectomy in the
      staging of penile cancer cases with nonpalpable groin nodes were assessed.
      MATERIALS AND METHODS: A modified inguinal lymph node dissection in which the
      saphenous vein is preserved together with reduction of the lateral, distal and
      proximal margins of dissection was performed on 12 consecutive men with invasive
      squamous carcinoma of the penis and negative inguinal nodes. RESULTS: Five
      patients were identified with nodal metastasis. The sites of inguinal node
      involvement were localized within the boundaries of the dissection in all
      patients. No major complications occurred, and no permanent lymphedema or flap
      necrosis was encountered. With a followup of 14 to 72 months no patient has had
      recurrent disease. CONCLUSIONS: The modified inguinal dissection is a reliable
      staging technique that also provides therapeutic benefit to patients with penile
      cancer and clinically negative nodes.

PMID- 8558661
TI  - Quantitative analysis of testicular histology in patients with vas deferens
      obstruction caused by childhood inguinal herniorrhaphy: comparison to
      vasectomized men.
AB  - PURPOSE: We investigated the effects on spermatogenesis of lifelong vas deferens
      obstruction caused by childhood inguinal herniorrhaphy. MATERIALS AND METHODS:
      Testicular histology was analyzed quantitatively in 15 post-herniorrhaphy
      patients with vasal obstruction for a mean of 28.5 years (group 1). The results
      were compared to those of 19 vasectomy patients with obstruction for a mean of
      8.2 years (group 2). RESULTS: There were significantly fewer total germ cells per
      tubular cross section in group 1 than in group 2 (p < 0.05). There was a
      significant negative correlation between the duration of obstruction and total
      germ cells per tubule (r = -0.389, p < 0.03, 34 patients). The tubular diameter
      was significantly larger in group 2 than in group 1 (p < 0.01). CONCLUSIONS:
      Patients with vas deferens obstruction caused by childhood inguinal herniorrhaphy
      have decreased spermatogenesis compared to post-vasectomy patients, probably due
      to the longer obstruction period.

PMID- 8558662
TI  - Optimal dose and duration of exposure to artificial stimulants in cryopreserved
      human spermatozoa.
AB  - PURPOSE: Poor sperm motility after cryopreservation is associated with
      infertility. For any pharmacological stimulation to be of clinical value, its
      effect in enhancing motility and other motion characteristics should be
      maintained for at least 1 hour. MATERIALS AND METHODS: Three motility stimulants
      (pentoxifylline, caffeine and 2-deoxyadenosine) were incubated with post-thaw
      semen samples from 11 healthy donors for 0, 30, 60, 120 and 180 minutes. The
      final concentrations used were 2.5 mM., 5 mM. and 10 mM. for pentoxifylline; 1
      mM., 2 mM. and 5 mM. for caffeine, and 0.5 mM., 1 mM. and 2.5 mM. for 2
      deoxyadenosine. Percent motility and changes in motion characteristics were
      measured on a computer assisted semen analyzer. RESULTS: Compared to controls (0
      minutes, no stimulant), an immediate increase in motility and other motion
      parameters was noted with all 3 stimulants. All stimulants caused a significant
      increase in percentage motility at all periods studied (p < 0.01). Similarly,
      pentoxifylline increased other motion parameters at the 2.5 mM. concentration (p
      < 0.01), caffeine was effective in increasing curvilinear velocity, average path
      velocity and amplitude of lateral head displacement (p < 0.01) at 5 mM., and 1
      and 2.5 mM. of 2-deoxyadenosine increased the curvilinear velocity, straight line
      velocity, average path velocity and amplitude of lateral head displacement (p <
      0.01). Among all stimulants only 2-deoxyadenosine increased linearity only at the
      1 mM. concentration. CONCLUSIONS: Our study suggests that these stimulants, when
      used at optimum concentrations, can maintain the improved sperm quality for
      durations longer than the minimum needed for fertilization. This finding may be
      significant in improving the poor semen quality observed after cryopreservation
      in oligospermic samples and in semen specimens from cancer patients.

PMID- 8558663
TI  - Psychosocial aspects in long-term survivors of testicular cancer.
AB  - PURPOSE: We assessed the psychosocial well-being in cured testicular cancer
      patients who had undergone chemotherapy with or without retroperitoneal lymph
      node dissection, radiotherapy or surveillance therapy. MATERIALS AND METHODS: The
      sample consisted of 83 cured testicular cancer patients of whom 34 had undergone
      cisplatin-based combination chemotherapy with or without retroperitoneal lymph
      node dissection (chemotherapy group), 42 had received infradiaphragmatic
      radiotherapy (radiotherapy group) and 7 had received surveillance therapy
      (surveillance group). The questionnaire reported demographic data, psychosocial
      well-being, working ability, satisfaction with life, relationships, and general
      health and fitness. RESULTS: For questions dealing with psychological distress
      there were no differences among the groups. However, a significant number of
      patients in all groups reported greater feelings of anxiety about health and
      future since treatment. Working ability was significantly better in the
      chemotherapy and radiotherapy groups than in the surveillance group (p < 0.05 and
      p < 0.01, respectively). Interestingly, the patients who received the most
      extensive treatment (chemotherapy plus retroperitoneal lymph node dissection)
      reported the best working ability. Using the satisfaction with life scale,
      patients in the chemotherapy and radiotherapy groups showed significantly higher
      scores than those in the surveillance group (p < 0.05). The majority of the
      patients reported no significant change in long-term relationships with family,
      friends and spouse. CONCLUSIONS: The development of psychosocial problems during
      long-term adjustment seems to be low regardless of treatment received. Although a
      significant number of patients reported a higher incidence of anxiety and
      depression since the illness, the overall attitude was positive toward life. With
      regard to treatment type, patients in the chemotherapy and radiotherapy groups
      had better working ability and greater satisfaction with life than the
      surveillance group.

PMID- 8558664
TI  - Tumor proliferative activity is predictive of pathological stage in clinical
      stage A nonseminomatous testicular germ cell tumors.
AB  - PURPOSE: Traditional histopathological features have failed to predict accurately
      the pathological stage of clinical stage A nonseminomatous germ cell tumors of
      the testis. Based on pilot studies in nonconsecutive patients at our university,
      we evaluated nontraditional risk factors (cell cycle analysis by flow cytometry,
      deoxyribonucleic acid analysis by single cell cytophotometry [image analysis] and
      assessment of proliferative activity by immunohistochemistry) combined with
      histopathological features in consecutive patients with clinical stage A
      nonseminomatous testis cancer. MATERIALS AND METHODS: Orchiectomy specimens from
      105 consecutive patients with clinical stage A nonseminomatous germ cell tumors
      who underwent retroperitoneal lymph node dissection (76 with pathological stage A
      disease and 29 with proved metastasis) were recut, histopathologically reviewed,
      immunohistochemically stained with proliferation markers (for example Ki-67/MIB
      1), and examined by flow cytometry and image analysis. RESULTS: After multiple
      logistic regression analysis, the G2M+S cell cycle fraction of the aneuploid
      tumor stemline was the most predictive parameter of pathological stage (p =
      0.0004). Using a cutoff of 41%, patients with metastasis were predicted with a
      sensitivity of 71%. Of 61 patients with a G2M+S value of less than 41%, 53 had
      pathological stage A cancer (negative predictive value 87%). A low volume of
      embryonal carcinoma was predominant in patients at low risk for metastasis and
      MIB-1 immunohistochemical staining identified 23% of patients with pathological
      stage A tumor who were at extremely low risk for metastatic disease. CONCLUSIONS:
      Assessment of tumor cell proliferation cannot classify accurately high risk
      patients at a clinically applicable level. However, identification of patients at
      low risk for metastasis by flow cytometry, immunohistochemical proliferation
      markers and volume of embryonal carcinoma may be possible at the 90% level. MIB-1
      staining is able to classify patients at extremely low risk for metastasis. These
      parameters deserve further study, since identification of patients at extremely
      low risk for metastasis could potentially decrease overall morbidity in the
      management of clinical stage A nonseminomatous testis cancer.

PMID- 8558665
TI  - The management of patients with clinical stage I nonseminomatous testicular
      tumors and persistently elevated serologic markers.
AB  - PURPOSE: We reviewed our experience with patients who had nonseminomatous germ
      cell tumors clinically limited to the testis and persistently elevated serum
      human chorionic gonadotropin (HCG) or alpha-fetoprotein (AFP) levels after
      orchiectomy. MATERIALS AND METHODS: All patients had clinical stage I disease
      with persistently elevated tumor markers that were not decreasing in accordance
      with the expected metabolic decay rate at retroperitoneal lymph node dissection.
      RESULTS: Of 30 patients identified 3 had elevated AFP, 24 had elevated HCG and 3
      had elevation of both markers. Of the 6 patients with elevated AFP with or
      without concurrent HCG elevation 5 (83%) had relapse and required chemotherapy,
      as did 6 of 24 (25%) with HCG elevation. CONCLUSIONS: Patients with persistently
      elevated AFP after orchiectomy should be treated initially with chemotherapy.
      Although the majority of patients with elevated serum HCG were disease-free after
      surgery alone, a fourth of these patients still had relapse and required
      chemotherapy.

PMID- 8558666
TI  - Incidence and management of testicular carcinoma metastatic to the neck.
AB  - PURPOSE: We evaluated the incidence and impact on outcome of neck metastasis in
      germ cell carcinoma. MATERIALS AND METHODS: A retrospective, institutional
      analysis of patients who presented with germ cell neoplasms was performed.
      RESULTS: During an 11-year period 7 of 155 patients (4.5%) with testis cancer had
      neck metastasis. The incidence of neck metastasis strongly correlated with
      disease stage. Selective neck dissection in 3 patients with post-chemotherapy
      residual neck masses demonstrated teratomatous elements in 2, with scar and
      necrosis in 1. CONCLUSIONS: Post-chemotherapy neck masses should be treated by
      definitive surgery for local disease control and to eliminate the possibility of
      residual neoplastic or teratomatous elements.

PMID- 8558667
TI  - Testis cancer--progress in risk assessment for occult retroperitoneal lymph node
      metastases.

PMID- 8558668
TI  - Natural history of prostatism: longitudinal changes in voiding symptoms in
      community dwelling men.
AB  - PURPOSE: We report the results of 3 contacts during 42 months of The Olmsted
      County Study of Urinary Symptoms and Health Status Among Men, a longitudinal
      cohort study of men 40 to 79 years old that was initiated in 1990 to describe
      changes in lower urinary tract symptom severity. MATERIALS AND METHODS: At
      baseline and followup, men completed questionnaires that elicited urinary symptom
      severity with questions nearly identical to those of the American Urological
      Association symptom index: RESULTS: Overall, there was an average increase in
      American Urological Association symptom index of approximately 0.18 (95%
      confidence interval 0.13 to 0.24) points per year of followup. The average annual
      symptom score slope and variability in slope increased with patient age at
      baseline from a mean of 0.05 +/- 1.06 (standard deviation) per year among men in
      the forties to 0.44 +/- 1.35 per year for men in the sixties, and decreased to
      0.14 +/- 1.42 per year for men in the seventies. The age-related changes in
      symptom severity mirror previous estimates of prostatic growth from autopsy
      prevalence studies. CONCLUSIONS: These results demonstrate a slow but measurable
      progression in urinary symptom severity among community dwelling men for 42
      months of followup.

PMID- 8558669
TI  - Primary care practitioners: an analysis of their perceptions of voiding
      dysfunction and prostate cancer.
AB  - PURPOSE: We analyzed practice and referral patterns of primary care practitioners
      regarding the diagnosis of prostate cancer, and the evaluation and treatment of
      voiding dysfunction. MATERIALS AND METHODS: An anonymous multiple-choice
      questionnaire was mailed to all primary care practitioners in Brooklyn, New York
      who were registered with the Medical Society of the State of New York. RESULTS:
      More than 25% of primary care practitioners begin performing digital rectal
      examination after patient age 55 years. Compared to prostate specific antigen
      (PSA) 59% of practitioners believe that digital rectal examination is more
      sensitive or that the tests are equal, or they do not know. In regard to PSA 11%
      of respondents begin testing after patient age 60 years, 11% evaluate PSA only if
      digital rectal examination is abnormal and greater than 3% never evaluate PSA.
      Approximately 45% of primary care practitioners indicated that PSA of greater
      than 4.0 ng./ml. signifies prostate cancer regardless of patient age, prostate
      size or prostatis and 50% think that digital rectal examination elevates PSA in a
      clinically significant way. Although 93.2% of respondents refer a patient to a
      urologist after palpating a prostatic nodule, only 51.1% refer for an area of
      induration. Of the 47.2% of respondents who attempt pharmacotherapy for voiding
      dysfunction with finasteride, terazosin or both 15% do not know the agent
      mechanisms of action. Of those prescribing finasteride 68.6% are not aware of its
      effects on serum PSA. Overall 66.5% of primary care practitioners are not
      familiar with the American Urological Association Symptom Index while only 15% of
      those attempting pharmacotherapy use the index as a diagnostic tool. CONCLUSIONS:
      Primary care practitioners might require further education in regard to the use
      of PSA, digital rectal examination and pharmacotherapy in voiding dysfunction.
      Consideration should be given to the establishment of guidelines for urological
      referral.

PMID- 8558670
TI  - Value of systematic transition zone biopsies in the early detection of prostate
      cancer.
AB  - PURPOSE: A prospective study was done to determine the value of performing 2
      systematic transition zone biopsies in addition to systematic sextant peripheral
      zone biopsies for early detection of prostate cancer. MATERIALS AND METHODS: From
      January 1 to August 31, 1994 we evaluated 847 consecutive patients referred to us
      for a suspicious lesion on digital rectal examination or an elevated serum
      prostate specific antigen level. All patients underwent 2 systematic transition
      zone biopsies in addition to systematic sextant biopsies of the peripheral zone.
      RESULTS: Of the transition zone biopsies 68 (24.4%) contained malignancy,
      including only 8 (2.9%) with cancer found exclusively in the transition zone. The
      remaining 271 cases (97.1%) had 1 or more positive peripheral zone biopsies and
      would have been detected with or without additional systematic transition zone
      biopsies. The same analysis of 552 patients with a negative digital rectal
      examination yielded 6 (4.1%) exclusively transition zone tumors among 145 cancers
      detected in this group. CONCLUSIONS: The low additional yield of transition zone
      biopsies (2.9 to 4.1%) does not warrant their systematic use for the early
      detection of prostate cancer.

PMID- 8558671
TI  - Transrectal ultrasound guided prostatic nerve blockade eases systematic needle
      biopsy of the prostate.
AB  - PURPOSE: We assessed the effect of transrectal ultrasound guided prostatic nerve
      blockade on the discomfort associated with systematic needle biopsy of the
      prostate. MATERIALS AND METHODS: A prospective randomized double-blind study was
      performed of 64 patients requiring systematic biopsy of the prostate. Patients
      were randomly assigned to receive an injection of 5 ml. 1% lidocaine or 5 ml.
      saline (0.9% sodium chloride) at the vascular pedicle on 1 side of the prostate
      only. They were then asked to score the severity of discomfort of the injection
      and subsequent biopsies on each side. RESULTS: Mean pain scores were
      significantly lower on the side with than the side without lidocaine injection
      (1.6 +/- 0.9 versus 2.4 +/- 1.2, p < 0.0001) and not significantly different when
      saline was injected (2.9 +/- 1.2 versus 3.0 +/- 1.1, p = 0.52). Pain scores were
      significantly different when the lidocaine injected side was compared to the
      saline solution injected side (p < 0.0001) but the difference was not significant
      between the noninjected sides of the 2 groups (p = 0.076). Of the patients in the
      lidocaine group 68% reported that they would prefer to undergo biopsy with the
      injection compared to only 41% in the placebo group (p = 0.037). During the study
      no patient in either group had any adverse effect from the injection.
      CONCLUSIONS: Transrectal ultrasound guided nerve blockade before prostatic biopsy
      results in a more comfortable procedure for the patient.

PMID- 8558672
TI  - Prostate cancer--educating ourselves and our nonurological colleagues.

PMID- 8558673
TI  - Radical perineal prostatectomy without pelvic lymphadenectomy: selection criteria
      and early results.
AB  - PURPOSE: We evaluated the surgical efficacy of radical perineal prostatectomy and
      determined preoperative parameters to identify patients at low risk for nodal
      metastasis. MATERIALS AND METHODS: Of 155 men evaluated for radical perineal
      prostatectomy, 74 were assigned to a low risk category (prostate specific antigen
      less than 10 ng./ml., Gleason score less than 7). Of the patients 40 underwent
      laparoscopic lymph node dissection and 34 did not. This group was compared to 81
      patients who underwent surgical staging and did not fit the low risk criteria.
      RESULTS: None of 74 patients in the low risk group had nodal metastasis, while
      metastasis was present in 5 of 81 (6.1%) who did not meet such parameters. Organ
      confined disease was present in 71.6% of men with low risk criteria, which was a
      significantly different rate than the 51.9% found in the other 81 men.
      CONCLUSIONS: Radical perineal prostatectomy confers adequate cancer control and
      can be performed without pelvic node dissection in select patients.

PMID- 8558674
TI  - Impact of moderate dose of postoperative radiation on urinary continence and
      potency in patients with prostate cancer treated with nerve sparing
      prostatectomy.
AB  - PURPOSE: We analyzed the impact on potency and urinary continence of moderate
      doses of radiation (45 to 54 Gy.) given postoperatively after nerve sparing
      prostatectomy. MATERIALS AND METHODS: Between 1983 and 1992, 294 of 762 prostate
      cancer patients were selected to undergo nerve sparing prostatectomy. Subjective
      patient reports regarding potency and urinary continence status were obtained
      preoperatively, 1 year postoperatively or 1 year after completion of radiation.
      RESULTS: Of the 294 patients 105 received postoperative radiotherapy (45 to 54
      Gy.) to the prostatic bed. There were patients with more advanced stages of
      disease in the irradiated group, including 89% with stages C and D1 (pT3N0 and
      pT1 to 3, N1 to 3), compared to 14% with stages C and D1 (pT3N0 and pT1 to 3, N1
      to 3) in the nonirradiated group (p < 0.001). No difference in urinary continence
      was noted in the irradiated (94%) compared to the nonirradiated group (92%, p =
      0.64). Of the patients who underwent bilateral nerve sparing prostatectomy 44%
      who received and 48% who did not receive radiation had recovered potency at 1
      year (p = 0.76). Of those who underwent unilateral nerve sparing prostatectomy
      10% who received and 33% who did not receive radiation had recovered potency at 1
      year (p = 0.14). Using multivariate analysis patient age younger than 63 years
      and bilateral versus unilateral nerve sparing procedures were significant
      predictors of potency. CONCLUSIONS: Our retrospective study suggests that at 1
      year after treatment moderate doses of postoperative radiotherapy did not have a
      significant impact on the recovery of urinary continence and potency after nerve
      sparing prostatectomy. However, longer followup is required to determine the
      impact of this radiation protocol on long-term preservation of potency after
      nerve sparing prostatectomy.

PMID- 8558675
TI  - Characterization of patients with androgen-independent prostatic carcinoma whose
      serum prostate specific antigen decreased following flutamide withdrawal.
AB  - PURPOSE: We confirmed the reported rate of prostate specific antigen (PSA)
      suppression after flutamide withdrawal in patients with metastatic prostatic
      carcinoma, increasing serum PSA and tumor progression following treatment with
      total androgen blockade (castration and flutamide). The value of clinical
      variables in predicting the rate of PSA decrease after flutamide withdrawal was
      assessed and adrenal androgen metabolism was correlated with the rate of PSA
      suppression following flutamide withdrawal. MATERIALS AND METHODS: A total of 41
      consecutive patients with metastatic prostatic adenocarcinoma and an increasing
      serum PSA while effectively castrated (plasma testosterone level less than 50
      ng./ml.) who were receiving 250 mg. flutamide 3 times daily was evaluated
      prospectively before cessation of the flutamide. Responses were determined at 6
      weeks. Only 2 of the 41 study patients (3%) had stable disease at 6 weeks, that
      is they had not met objective criteria for response or progression at analysis.
      RESULTS: Of 39 patients studied 11 (28.2%, 95% confidence internal 14 to 45%) had
      a PSA decrease (more than 50% from baseline) following flutamide withdrawal and
      they were treated with initial complete androgen blockade. Median duration of PSA
      decrease was only 13 weeks (range 7 to 52), and 3 of the 11 patients had
      continued suppression of serum PSA concentrations at 12+, 13+ and 20+ weeks. The
      serum PSA decrease was associated with improved clinical symptoms, although
      objective regression of the disease was found in only 1 to 2 patients with
      measurable disease. No statistical correlation between endocrine studies or serum
      bombesin secretion and PSA decrease was found, although patients with a PSA
      decrease after flutamide withdrawal tended to have a lower dehydroepiandrosterone
      concentration than those with PSA progression. No correlation between known
      prognostic variables and decreased serum PSA after flutamide withdrawal was
      detected. CONCLUSIONS: We confirmed the existence of the reported paradoxical PSA
      decrease in patients with androgen-independent carcinoma of the prostate, and
      that the delivery of simultaneous initial flutamide with castration predicts for
      PSA decrease. Individual patients appear to benefit from flutamide withdrawal
      although the overall impact was slight. The differences in frequency compared to
      those reported by others may be accounted for by patient selection and the number
      of patients receiving sequential castration therapy followed by flutamide.

PMID- 8558677
TI  - Strategies to manage prostate cancer.

PMID- 8558676
TI  - 5-fluorouracil and allopurinol combined with recombinant interferon-alpha 2b in
      the treatment of patients with advanced prostate cancer: a phase I/II study.
AB  - PURPOSE: We determined the toxicity and preliminary response rate of escalating
      doses of 5-fluorouracil (670 to 1,500 mg./m.2 per day) combined with a fixed dose
      of interferon-alpha 2b (5 million units) and allopurinol (300 mg. every 8 hours)
      in cohorts of patients with metastatic prostate cancer. MATERIALS AND METHODS:
      The trial included 11 men with metastatic prostate cancer. Cohorts of patients
      received a 5-day constant infusion of 5-fluorouracil combined with subcutaneous
      interferon-alpha 2b 3 times weekly and allopurinol for 1 week during 5
      fluorouracil infusion. Treatment was repeat every 3 weeks. RESULTS: Of 10
      patients evaluable for treatment response and toxicity 3 had a partial response
      as judged by significant decreases in prostate specific antigen measurements
      (mean followup 13.5 months). Significant dose limiting toxicities encountered
      included mucositis, diarrhea and leukoneutropenia. CONCLUSIONS: Further
      evaluation of this treatment to determine overall response rates and benefit
      should take into consideration the significant toxicity experienced.

PMID- 8558678
TI  - Direct measurement of blood flow in the human bladder.
AB  - PURPOSE: We evaluated blood flow in the human bladder. MATERIALS AND METHODS: In
      8 surgical cases a laser Doppler flow probe was placed in the bladder dome and
      anterior wall. In 10 endoscopic cases the flow probe was placed in the bladder
      trigone and lateral wall. RESULTS: Bladder filling resulted in reduced mean blood
      flow in the dome and anterior wall. After prostatectomy blood flow decreased in
      the dome but not the anterior wall. During endoscopy bladder filling resulted in
      diminished blood flow. CONCLUSIONS: Laser Doppler flowmetry can measure blood
      flow changes in the human bladder.

PMID- 8558679
TI  - Urological symptomatology in patients with reflex sympathetic dystrophy.
AB  - PURPOSE: We determined the effect of reflex sympathetic dystrophy on lower
      urinary tract function. MATERIALS AND METHODS: A total of 20 consecutive patients
      (16 women and 4 men) with neurologically verified reflex sympathetic dystrophy
      was referred for voiding symptoms, including urgency, frequency, incontinence and
      urinary retention. No patient had had voiding symptoms before the initial trauma
      that induced reflex sympathetic dystrophy. Evaluation included medical history,
      physical examination, video urodynamic testing and cystoscopy. RESULTS: Mean
      patient age was 43.4 +/- 10.2 years (range 28 to 58) and mean duration of
      urological symptoms was 4.9 +/- 3.6 years (range 1 to 14). Urodynamic study
      demonstrated a mean cystometric bladder capacity of 417 +/- 182 ml. (range 120 to
      700). The urodynamic diagnoses included detrusor hyperreflexia in 8 patients,
      detrusor areflexia in 8, sensory urgency in 3 and detrusor hyperreflexia with
      detrusor-external sphincter dyssynergia in 1. In 4 women genuine stress urinary
      incontinence was also documented urodynamically. CONCLUSIONS: Reflex sympathetic
      dystrophy may have a profound effect on detrusor and sphincter function.

PMID- 8558680
TI  - A functioning adrenocortical hemangioma.

PMID- 8558681
TI  - Spontaneous retroperitoneal hemorrhage from a giant adrenal myelolipoma.

PMID- 8558682
TI  - Nearly fatal injury of iliac artery after inaccurate incision of
      ureterointestinal stricture in orthotopic neobladder.

PMID- 8558683
TI  - Inverted Y duplication of the ureter with associated ureterocele and bladder
      outlet obstruction.

PMID- 8558684
TI  - Focal emphysematous cystitis arising in a diverticulum: a case report.

PMID- 8558685
TI  - An unusual pelvic pseudotumor: a case report.

PMID- 8558686
TI  - Spontaneous perforation of the bladder after external beam radiotherapy for
      bladder carcinoma.

PMID- 8558687
TI  - Urethral pseudolipoma: a complication of periurethral lipo-injection for stress
      urinary incontinence in a woman.

PMID- 8558688
TI  - Complete penile corporeal septation.

PMID- 8558689
TI  - Testicular carcinoma in a patient with previously demonstrated testicular
      microlithiasis.

PMID- 8558690
TI  - Malignant peripheral nerve sheath tumor of the scrotum: a case report.

PMID- 8558691
TI  - Paraganglioma of the spermatic cord: report of a case.

PMID- 8558692
TI  - The effect of low dose finasteride therapy in a man with prostatism.

PMID- 8558693
TI  - Spontaneous remission of a bony metastasis in prostatic adenocarcinoma.

PMID- 8558694
TI  - Urinary tract infection with an unusual pathogen (Nocardia asteroides).

PMID- 8558695
TI  - Re: Fournier's gangrene in a patient with erectile dysfunction following use of a
      mechanical erection aid device.

PMID- 8558696
TI  - Re: The syndrome of dysuria and hematuria in pediatric urinary reconstruction
      with stomach.

PMID- 8558697
TI  - Renal tubular abnormalities in infants with hydronephrosis.
AB  - PURPOSE: Abnormalities in renal tubular function have been observed in
      hydronephrotic urinary tract disease, resulting in metabolic acidosis,
      hyperkalemia and excessive free water diuresis. The frequency of these
      abnormalities, particularly in our infant population, was the impetus for our
      study. MATERIALS AND METHODS: We studied 50 infants selected from 199 patients
      followed for hydronephrosis before any surgical intervention during a 5-year
      period. Mean patient age was 1.5 +/- 1.0 months at the time of diagnosis by
      ultrasound, voiding cystourethrography and a radionuclide renal scan. Lesions
      were classified as unilateral or bilateral and graded according to severity of
      renal pelvic dilatation or grade of vesicoureteral reflux. RESULTS: At least 1
      abnormality of tubular function was present in 29 patients (58%) of whom the
      predominant abnormality was renal tubular acidosis in 23 (79%, 46% of the total
      study group). Renal tubular acidosis was diagnosed on the basis of a serum total
      carbon dioxide of 19 mM./l. or less with urinary pH 5.5 or greater. The defect
      appeared to be distal in most cases. Other abnormalities included defects in
      urinary concentrating ability in 10 patients (4 with unilateral urinary tract
      dilatation). Distal tubular aldosterone resistance in 6 patients (3 with
      unilateral dilatation) was demonstrated by hyperkalemia with a low transtubular
      potassium gradient of 3 or less and low fractional excretion of potassium.
      Although common in unilateral lesions, renal tubular dysfunction became more
      prevalent with an increase in severity score and bilaterality. CONCLUSIONS: Renal
      tubular dysfunction is frequent in hydronephrotic infants with unilateral or
      bilateral disease. Although rarely life threatening and usually self-limiting,
      the metabolic consequences of these abnormalities require investigation to allow
      for appropriate medical management.

PMID- 8558698
TI  - Detection of permanent damage in kidneys with vesicoureteral reflux by
      quantitative single photon emission computerized tomography (SPECT) uptake of
      99mtechnetium labeled dimercaptosuccinic acid.
AB  - PURPOSE: We determined the level of functional damage to the kidney which
      inhibits further growth. MATERIALS AND METHODS: Renal functional volume and
      percent uptake of 34 kidneys with reflux were studied by performing sequential
      quantitative single photon emission computerized tomography 2 times at a mean
      interval of 3.2 years. RESULTS: Change in volume between the initial and repeat
      studies was 27.2 +/- 28.4% in all 34 kidneys. Change in volume was less than 7%
      in 8 kidneys and greater than 14% in 26. Receiver operating characteristic curve
      analysis indicated that 15.6% kidney uptake was associated with 75% sensitivity,
      100% specificity and 94% accuracy in distinguishing kidneys with more than 7%
      from those with less than 7% change in volume. The value of kidney uptake of less
      than 15.6% was 100% in predicting less than 7% change in volume (positive
      predictive value) and the value of kidney uptake greater than 15.6% was 93% in
      predicting more than 7% change in volume (negative predictive value).
      CONCLUSIONS: Kidney uptake of less than 15.6% represents irreversible impairment
      of renal growth and indicates permanent damage in kidneys with vesicoureteral
      reflux.

PMID- 8558699
TI  - Gross bilateral reflux in infants: gradual decrease of initial detrusor
      hypercontractility.
AB  - PURPOSE: We performed followup investigations of the urodynamic patterns of 11
      boys with gross bilateral reflux, which are sometimes characterized by low
      bladder capacity and hypercontractility of the detrusor. MATERIALS AND METHODS:
      Urodynamic evaluations were done a mean of 2 years after the initial assessment
      during infancy. RESULTS: Initial hypercontractility resolved and bladder capacity
      increased from below normal to high in the majority of cases. The number of
      children with instability did not change significantly. CONCLUSIONS: The
      urodynamic pattern at followup was similar to that previously reported as the
      most common dysfunction in older children with reflux.

PMID- 8558700
TI  - Transient urodynamic dysfunction of infancy: relationship to urinary tract
      infections and vesicoureteral reflux.
AB  - PURPOSE: Urinary tract infections and vesicoureteral reflux are more common in
      male than female infants. Since these problems can result from voiding
      dysfunction, we obtained a detailed history of voiding patterns and urodynamic
      testing in infants with urinary tract infections in the first year of life.
      MATERIALS AND METHODS: We evaluated 39 male and 22 female infants, including 40
      with primary vesicoureteral reflux and 21 with no reflux or obstruction. RESULTS:
      Voiding abnormalities were noted in 97% of the male and 77% of the female
      infants, including high voiding detrusor pressure of greater than 40 cm. water in
      92% of the male and 66% of the female infants, residual urine greater than 2
      ml./kg. in 13% of the male and 23% of the female infants, and detrusor
      hyperreflexia with filling pressure greater than 40 cm. water in a third of the
      male infants. Voiding detrusor pressure was significantly higher in male than
      female infants and in male infants with grade IV to V reflux than those with
      lower grades of reflux or no reflux. Followup urodynamic testing in 15 infants
      with high voiding detrusor pressure revealed resolution of detrusor hyperreflexia
      and improvement in post-void residual in all and decreased voiding detrusor
      pressure in 14. CONCLUSIONS: We coined the term transient urodynamic dysfunction
      of infancy to describe this constellation of abnormalities, which predisposes
      infants to urinary tract infections and vesicoureteral reflux but improves
      spontaneously. The higher incidence of urinary tract infections and reflux in
      male infants may be related to higher intravesical pressures.

PMID- 8558701
TI  - Elevated interleukin-8 levels in the urine of children with renal scarring and/or
      vesicoureteral reflux.
AB  - PURPOSE: Elevation of urinary levels of interleukin-6 and 8 has been observed in
      patients with acute urinary tract infections. However, to our knowledge there
      have been no studies concerning the secretion of interleukin-6 and 8 into the
      urine after acute inflammation has resolved and renal scarring has occurred. On
      the other hand, it is well known that cytokines are variously related to
      glomerular diseases and, thus, it is possible that the progression of reflux
      nephropathy depends on interleukin-6 or 8. Therefore, we assessed urinary levels
      of interleukin-6 and 8 in children with vesicoureteral reflux and/or renal
      scarring. MATERIALS AND METHODS: We evaluated interleukin-6 and interleukin-8
      levels in the urine of 32 children without a urinary tract infection who
      presented or were admitted to our hospital because of vesicoureteral reflux
      between April and December 1994. Interleukin-6 and 8 were determined using a
      commercially available human enzyme-linked immunosorbent assay kit and the 2-step
      sandwich method. RESULTS: Urinary interleukin-6 levels were below the lower
      detection limit (less than 10 pg./ml.) in all samples. There were statistically
      significant differences between urinary interleukin-8 levels in children with and
      without renal scarring (p = 0.001), and with and without vesicoureteral reflux (p
      = 0.0246). CONCLUSIONS: Urinary interleukin-8 is an effective marker for renal
      scarring and vesicoureteral reflux.

PMID- 8558702
TI  - The tailored low dose fluoroscopic voiding cystogram for familial reflux
      screening.
AB  - PURPOSE: Radionuclide voiding cystography is generally advocated as a screening
      study to detect familial reflux. We assessed the efficacy of tailored low dose
      fluoroscopic voiding cystography for this purpose. MATERIALS AND METHODS: We
      evaluated 10 boys and 10 girls 9 months to 10 years old (mean age 5 years) who
      were siblings of patients known to have reflux. The technique used a low dose
      fluoroscopic system. A tailored voiding cystographic protocol was designed to
      minimize gonadal radiation dose. RESULTS: Absence of reflux was confirmed in 10
      patients. Mean fluoroscopy time was 19 seconds (range 14 to 22), resulting in
      mean gonadal radiation exposure of less than 1.5 mrad., which is comparable to
      the lowest reported doses with the radionuclide technique. After reflux was
      demonstrated in 10 patients the study was immediately converted to a standard
      fluoroscopic imaging technique to define lower tract anatomy and quantitate
      reflux, avoiding a second study. CONCLUSIONS: Tailored low dose fluoroscopic
      voiding cystography appears to be a practical approach for the assessment of
      familial reflux.

PMID- 8558703
TI  - The role of newer modalities in the diagnosis of vesicoureteral reflux.

PMID- 8558704
TI  - Hemorrhagic cystitis caused by acetic acid instillation.

PMID- 8558705
TI  - Ventriculoperitoneal shunt infection after augmentation cystoplasty.
AB  - PURPOSE: We characterized the occurrence of ventriculoperitoneal shunt infections
      after augmentation cystoplasty. MATERIALS AND METHODS: We reviewed the records of
      20 myelodysplastic children with ventriculoperitoneal shunts followed for a
      minimum of 12 months after augmentation. RESULTS: In 4 children (20%) a
      ventriculoperitoneal shunt infection developed. The single gram-positive
      infection occurred early (less than 30 days). The 3 gram-negative infections were
      delayed presentations (greater than 30 days). Organisms in 2 of the 3 gram
      negative infections had been noted in a preoperative urine culture. CONCLUSIONS:
      Ventriculoperitoneal shunt infection after bladder augmentation is common.
      Delayed presentation of shunt infections may indicate gram-negative infection.
      Sterilization of the urinary tract is indicated before augmentation.

PMID- 8558706
TI  - A combined vertical and horizontal pelvic osteotomy approach for primary and
      secondary repair of bladder exstrophy.
AB  - PURPOSE: We describe a new combined horizontal and vertical pelvic osteotomy
      procedure for bladder exstrophy. MATERIALS AND METHODS: A total of 36 patients
      with the bladder exstrophy complex underwent this procedure during a 3-year
      period (8 primary and 18 secondary bladder closures, and 6 at bladder neck
      reconstruction). RESULTS: There were no instances of dehiscence and only a minor
      bladder prolapse in 1 patient with cloacal exstrophy. Two patients had a
      transient femoral nerve palsy and there was 1 superficial pin infection.
      Urological complications included symptomatic urinary tract infections in 5
      patients, acute epididymitis in 1 and bladder calculi in 2. CONCLUSIONS: This new
      osteotomy procedure is of great benefit in initial or repeat closure of bladder
      exstrophy and may help in eventually achieving continence.

PMID- 8558707
TI  - Bladder dysfunction in boys with posterior urethral valves before and after
      puberty.
AB  - PURPOSE: We characterized bladder dysfunction in boys with posterior urethral
      valves during childhood and adolescence. MATERIALS AND METHODS: A total of 12
      prepubertal boys with posterior urethral valves presenting before age 1 year was
      followed from ages 4 to 14 years and compared to 6 postpubertal boys with
      posterior urethral valves. Urodynamic evaluations and renal function studies were
      performed repeatedly. RESULTS: Patients had a changing urodynamic pattern with
      instability decreasing with time, increasing bladder capacity and commonly an
      unsustained voiding contraction causing emptying difficulties. Postpubertal boys
      had high capacity bladders with low contractility. CONCLUSIONS: We suggest that
      previously described urodynamic patterns of the valve bladder (unstable, poorly
      compliant and over distended bladders) are variations of the same basic pattern
      that changes with time toward decompensation.

PMID- 8558708
TI  - Glutaraldehyde cross-linked collagen in the treatment of urinary incontinence in
      children.
AB  - PURPOSE: Prospective analysis was done to assess the efficacy of glutaraldehyde
      cross-linked collagen in the treatment of pediatric structural urinary
      incontinence. MATERIALS AND METHODS: A total of 40 pediatric patients (average
      age 12.1 years) with structural urinary incontinence received 70 glutaraldehyde
      cross-linked collagen injections. Of the 40 patients 25 had spina bifida, 12 had
      the exstrophy/epispadias complex, 2 had continent reservoirs and 1 had bilateral
      ureteral ectopia. Average followup was 2.1 years (range 3 months to 6.3 years),
      and included urodynamic evaluation and assessment of change in continence grade,
      daily pad use and dry interval. Patient satisfaction was evaluated by
      questionnaire concerning self-esteem, activity level and patient assessment of
      overall benefit. RESULTS: Complete cure of incontinence was reported by 22% of
      patients, improvement by 54% and no change by 24%. There was statistically
      significant postoperative improvement of continence grade (exstrophy/epispadias p
      < or = 0.004, spina bifida p < or = 0.0001), decreased daily use of pads
      (exstrophy/epispadias p < or = 0.008, spina bifida p < or = 0.002) and dry
      interval (exstrophy/epispadias p < or = 0.008, spina bifida p < or = 0.004).
      Greater success occurred in cases of the exstrophy/epispadias complex (91%) than
      spina bifida (71%). No patient had unsafe bladder pressures as a result of
      collagen treatment. Reevaluation of a 1992 study group with an initial 88% cure
      or improvement rate showed that after a mean followup of 4.5 years the cure or
      improvement rate remained 86%. CONCLUSIONS: Collagen improves continence in the
      majority of children with anatomically based urinary incontinence.
      Exstrophy/epispadias patients have the best outcome from collagen treatment.
      Glutaraldehyde cross-linked collagen is durable in most patients who have an
      initially positive outcome.

PMID- 8558709
TI  - Satisfaction with penile appearance after hypospadias surgery: the patient and
      surgeon view.
AB  - PURPOSE: We studied the degree of agreement between hypospadias patient and
      surgeon satisfaction with the cosmetic surgical result, and the relation between
      penile length, meatal position and patient satisfaction. MATERIALS AND METHODS:
      Cosmetic and functional results in 35 boys with hypospadias were assessed, and a
      standardized questionnaire was completed by patients and surgeon. RESULTS: There
      was hardly any agreement between patient and surgeon satisfaction with patient
      penile appearance. Patients were less satisfied than the surgeon. No significant
      correlation was noted between penile satisfaction and penile length. Patients
      with a retracted meatus were less satisfied with the meatal position than those
      with a glanular meatus. Of the 35 patients 4 underwent repeat surgery after our
      study. CONCLUSIONS: Hypospadias surgeons should explicitly asked if patients are
      satisfied and they should follow patients through adolescence.

PMID- 8558710
TI  - Glomus tumor of the penis.

PMID- 8558711
TI  - Laparoscopic orchiopexy: clinical experience and description of technique.
AB  - PURPOSE: We reviewed the experience, early followup and technique of laparoscopic
      treatment of the nonpalpable undescended testis at our institution. MATERIALS AND
      METHODS: Charts of patients who underwent laparoscopic treatment of an intra
      abdominal testis from September 1992 to October 1994 were reviewed. RESULTS: A
      total of 13 laparoscopic orchiopexies was performed on 11 children with
      nonpalpable undescended testes. In 10 cases sufficient length was gained on the
      spermatic vessels using laparoscopic dissection to perform tension-free
      orchiopexy without the need for division of the spermatic vessels. CONCLUSIONS:
      When localization of an intra-abdominal testis is confirmed, orchiopexy can be
      performed safely with minimal morbidity using a laparoscopic approach. Length of
      hospital stay and postoperative morbidity may be improved in comparison to
      traditional techniques.

PMID- 8558712
TI  - The remnant orchiectomy.
AB  - PURPOSE: We examined and characterized the histological features of remnant
      testicular tissue distal to the internal inguinal ring in boys who underwent
      exploration for a nonpalpable testis. MATERIALS AND METHODS: The medical records
      and histology of 48 boys (50 remnants) who underwent exploration for a
      nonpalpable testis during a 10-year period were reviewed in detail. RESULTS:
      Remnant tissue was characterized by evidence of ischemia and necrosis (scar,
      calcification, hemosiderin and hyalinization) suggestive of a vascular accident.
      Viable germ cells were identified in 5 remnants. CONCLUSIONS: A 10% incidence of
      viable germ cells in remnant testicular tissue warrants exploration and removal
      of all remnant tissue in boys who undergo exploration for a nonpalpable testis.

PMID- 8558713
TI  - Evidence for a tumor suppressor gene distal to BRCA1 in prostate cancer.
AB  - PURPOSE: The breast-ovarian cancer susceptibility gene, BRCA1, has been
      implicated by both epidemiologic and genetic studies to be involved in prostate
      cancer. We wished to test the frequency of BRCA1 deletion and that of other
      markers in the region of proximal 17q in prostate tumor cells. MATERIALS AND
      METHODS: We used a dual-color fluorescence in situ hybridization (FISH) assay
      using P1 phage probes for the BRCA1 gene and 3 flanking sites at 17q12-21, as
      well as a chromosome 17 centromere-specific alpha-satellite probe, to detect
      deletions in single-cell suspensions and touch preparations from 23 primary
      clinical stage B prostate tumors and adjacent nontumor prostate tissues.
      Lymphoblastoid cells and prostate cells from a normal donor were used to
      determine control loss values. RESULTS: Significant loss (p < 0.05) of at least 1
      of the P1s was detected in 16 of 23 (70%) cases, and in 4 of those cases all
      markers were lost, consistent with whole chromosome loss. Of the 12 cases with
      subchromosomal loss, 8 had loss distal to BRCA1. Loss was detected in 5 cases
      previously reported by using allelic imbalance (AI) methodologies, and was
      detected in an additional 11 non-AI cases, suggesting that FISH is more sensitive
      than AI for deletion detection in prostate tumor cells. CONCLUSIONS: The data
      suggest that the region distal to BRCA1 may contain 1 or more prostate-specific
      tumor suppressor genes and that BRCA1 itself plays only a minor role in prostate
      cancer development.

PMID- 8558714
TI  - The effects of cellular hypoxia on contraction and extracellular ion accumulation
      in isolated human detrusor smooth muscle.
AB  - PURPOSE: The effect of cellular hypoxia on the phasic isometric contraction of
      isolated preparations of human detrusor muscle was measured and the influence of
      the accumulation of extracellular H+ and K+ on the inotropic effects ascertained.
      MATERIAL AND METHODS: Strips of human detrusor smooth muscle were field
      stimulated and superfused with an HCO3-/CO2 medium. Cellular hypoxia was
      generated by superfusion with 1) a low PO2 (approximately 5 kPa) solution; 2) 5
      mM. Na azide; or 3) 10 mM. 2-deoxyglucose and omission of glucose and Na
      pyruvate. Extracellular pH or [K+] was simultaneously measured with ion-selective
      microelectrodes placed in the muscle strip. RESULTS: Interventions produced a
      reversible contractile decay in the steady state, but the decay was preceded by a
      transient increase of force in most preparations. A small rise of the
      extracellular [K+] was also measured, but the effect was significantly smaller
      with 2-deoxyglucose. Extracellular acidosis was recorded with low PO2 and Na
      azide, but was absent with 2-deoxyglucose. The extracellular acidosis was usually
      preceded by a transient extracellular alkalosis. CONCLUSION: Part of the
      contractile changes under these conditions could result from an extracellular
      acidosis generated via glycolysis; the accumulation of extracellular K+ was
      insufficient to exert inotropic effects.

PMID- 8558715
TI  - Genetic and cellular response to unilateral ischemia of the rabbit urinary
      bladder.
AB  - PURPOSE: Previous studies have demonstrated that partial outlet obstruction and
      acute overdistension of the rabbit bladder rapidly stimulate the activation of
      similar patterns of gene expression. Since bladder overdistension has been shown
      to reduce the blood flow of the bladder and since unilateral ischemia of rabbit
      bladder has been found to induce similar physiologic and histologic changes to
      the bladder as found in association with partial outlet obstruction, we tested
      whether experimental ischemia of the rabbit bladder could induce the same
      molecular response. MATERIAL AND METHODS: Unilateral ischemia was created by
      surgically ligating the major arteries entering the rabbit bladder to one side.
      Bladders were recovered from control rabbits and from rabbits at 1 hour, 8 hours,
      1, 3, or 7 days after unilateral ischemia and were divided into ischemic and
      nonischemic portions. These tissues were used for in vitro 35S-methionine and 3H
      thymidine incorporation assays. Ribonucleic acids extracted from these tissues
      were examined by Northern blot assay for the expression of a number of different
      mRNA transcripts. RESULTS: 1) Bladder DNA synthesis was elevated 4-fold at 24
      hours after ischemia; 2) protein synthesis was increased 2-fold at 8 and 24 hours
      after ischemia; 3) early response genes (c-fos and c-jun) mRNAs were induced by 1
      hour of ischemia; hsp-70 mRNA was highly induced by 8 hours of ischemia, and bFGF
      mRNA was elevated 3- to 5-fold by 8 hours of ischemia. CONCLUSION: The early
      molecular response of rabbit bladder to ischemia is similar to responses observed
      in bladder overdistension or partial outlet obstruction.

PMID- 8558716
TI  - Prostate specific antigen releases a kinin-like substance on proteolysis of
      seminal vesicle fluid that stimulates smooth muscle contraction.
AB  - PURPOSE: We investigated whether purified prostate specific antigen (PSA), a
      seminal plasma serine protease of the kallikrein enzyme family, is capable of
      releasing kinin-like peptides from natural substrate glycoproteins in human
      seminal vesicle fluid. MATERIALS AND METHODS: An in vivo rat bladder model was
      used to monitor for release of substances capable of inducing smooth muscle
      contractions. Purified PSA, seminal vesicle fluid (SVF) from radical
      prostatectomy specimens, bradykinin, saline and a bradykinin antagonist were
      injected intravesically into urethane-anesthetized rats, and the resulting
      bladder contractions were measured. RESULTS: Injection of either PSA or SVF alone
      did not induce bladder contractions. Injection of a mixture of SVF and PSA
      preincubated 15 minutes, however, induced strong bladder contractions (23 +/- 7
      cm. H2O) that decreased with time (4 +/- 2 cm. H2O, after 90 minutes). Similar
      contractions were observed after injection of bradykinin (10(-4) M. = 39 +/- 14,
      10(-6) M. = 27 +/- 9, 10(-8) M. = 7 +/- 4 cm. H2O). Addition of a bradykinin
      antagonist to the PSA-SVF mixture prior to injection blocked the observed bladder
      contractions (23 +/- 7 cm. H2O before, versus 0.3 +/- 1.2 cm. H2O after adding
      antagonist). CONCLUSIONS: We conclude that PSA produces a kinin-like substance by
      enzymatic cleavage of glycoproteins in human seminal fluid. This substance
      induces smooth muscle contractions which can be specifically blocked by addition
      of a bradykinin antagonist.

PMID- 8558717
TI  - The influence of cytokines on the adhesion of renal cancer cells to endothelium.
AB  - PURPOSE: The development of tumor metastasis requires direct adhesive
      interactions between tumor cells and vascular endothelium. We examined the
      adherence of renal cell carcinoma (RCC) lines to endothelium after stimulation
      with different cytokines that induce expression of the vascular adhesion
      molecules endothelial leukocyte adhesion molecule (ELAM)-1, vascular cell
      adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1,
      MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) were used
      to determine the adhesion of the RCC lines CCF-RC1, 2 and 7 to endothelium.
      Expression of cell adhesion molecules (CAM) on HUVEC and RCC lines was measured
      with immunoflowcytometry. RESULTS: Stimulation of HUVEC with rIl-1 beta, rTNF
      alpha, or PMA resulted in a time-dependent 1.4- to 2.9-fold increase of RCC
      adhesion to HUVEC. Significant increased tumor cell binding was observed after 4
      hours and paralleled the time-dependent induction of ELAM-1 and VCAM-1.
      Immunocytometry demonstrated the presence of the ligands sialyl Lewis X and VLA-4
      on RCC, and blocking studies with monoclonal antibodies directed against tumor
      cell-endothelial interactions mediated by VCAM-1/VLA-4 and ELAM-1/sialyl Lewis X
      demonstrated marked inhibition of tumor cell adherence to cytokine-stimulated
      HUVEC. CONCLUSIONS: This study demonstrates that cytokine-induced increases in
      RCC adherence to HUVEC are mediated in part by VCAM-1/VLA-4 and ELAM-1/sialyl
      Lewis X interactions and suggest that these molecules may play an important role
      in the ability of RCC to metastasize.

PMID- 8558718
TI  - Crystal-cell interaction inhibition by polysaccharides.
AB  - PURPOSE: We studied the effect of polysaccharides on interactions between calcium
      oxalate monohydrate (COM) crystals and cultured renal cells. MATERIALS AND
      METHODS: Monolayers of Madin-Darby canine kidney (MDCK) cells were incubated with
      radiolabeled crystals in the presence of various concentrations of natural
      glycosaminoglycans (GAGs) and semisynthetic polysaccharides (SSPs). RESULTS:
      While most GAGs were found to have relatively little effect, SSPs (SP54, G871 and
      G872) were potent inhibitors of crystal-cell association. Pretreatment of
      crystals, but not of cells, was similarly effective, suggesting polysaccharide
      induced modification of crystal surface properties. CONCLUSIONS: This result
      further supports the idea that SSPs, and especially G872, are of potential
      interest for treatment of recurrent stone disease.

PMID- 8558719
TI  - Adenoviral-p53 gene transfer to orthotopic and peritoneal murine bladder cancer.
AB  - PURPOSE: This study was designed to examine the potential for adenoviral-mediated
      gene therapy in primary and metastatic bladder cancer. MATERIALS AND METHODS:
      Orthotopic and intraperitoneal bladder tumors were established after delivery of
      1 x 10(6) MBT-2 cells into syngeneic mice. Gene transfer was accomplished via
      intravesical or intraperitoneal instillation by using an E-1 deleted adenovirus
      encoding LacZ or human p53. Successful tumor transduction was confirmed in tumor
      DNA and mRNA by polymerase chain reaction. Detection of recombinant gene product
      was detected by histochemical staining (X-gal) and Western blot. RESULTS:
      Palpable tumors developed 18 days following implantation. LacZ and p53 mRNA were
      present in tumor and adjacent normal tissue after bladder and intraperitoneal
      vector administration. Recombinant gene products were identified by
      histochemistry and Western blot. CONCLUSION: Bladder tumor-directed gene transfer
      using adenoviral vectors is an efficient and powerful tool for evaluating the
      adjuvant role of therapeutic gene products.

PMID- 8558720
TI  - Inhibition of human transitional cell carcinoma in vitro proliferation by
      fluoroquinolone antibiotics.
AB  - PURPOSE: The in vitro effects of the fluoroquinolone antibiotics ciprofloxacin
      and ofloxacin upon 3 human transitional cell carcinoma cell lines were
      investigated at concentrations that are attainable in the urine of patients
      taking these drugs orally. MATERIALS AND METHODS: Cell lines TCCSUP, T24, and J82
      were exposed in culture to either ciprofloxacin or ofloxacin at concentrations
      ranging from 0 to 800 micrograms./ml. and at durations ranging from 24 to 120
      hours. Inhibition of proliferation and DNA synthesis were assessed via MTT and
      tritiated thymidine assays, respectively. RESULTS: From the MTT assay
      ciprofloxacin, at concentrations of 25 to 800 micrograms./ml., produced
      proliferation inhibition in the TCCSUP line ranging from 8.1% to 90.2% at 24
      hours, 25.1% to 94.9% at 72 hours, and 53.8% to 96.9% at 120 hours. Inhibition of
      proliferation for the T24 line ranged from 8.0% to 85%, 31.5% to 96.5%, and 27.3%
      to 98.2%. Inhibition of proliferation of the J82 line ranged from 20.8% to 84.8%,
      22.8% to 92.7%, and 37.4% to 97.1%. Inhibition of DNA synthesis (due to
      ciprofloxacin at the concentrations above) as measured by the tritiated thymidine
      assay was also significant for each of the 3 cell lines. Inhibition of
      proliferation and DNA synthesis due to ofloxacin was lower but not overall
      statistically different from that due to ciprofloxacin. In a separate experiment,
      enhanced cytotoxicity was observed at lower concentrations of ciprofloxacin when
      the initial media pH was approximated to 5.5. CONCLUSIONS: Ciprofloxacin and
      ofloxacin inhibit proliferation and DNA synthesis of these 3 human TCC lines in
      vitro. Inhibition occurred in a concentration- and time-dependent manner. The
      concentrations that were assessed are attainable in the urine of patients taking
      these agents orally.

PMID- 8558721
TI  - Nitric oxide inhibits contraction of isolated pig ureteral smooth muscle.
AB  - PURPOSE: To investigate the L-arginine/nitric oxide (NO) pathway in the pig
      isolated ureter. MATERIALS AND METHODS: Functional inhibitory effects mediated by
      NO were assessed and correlated with cyclic nucleotide levels. Nitric oxide
      synthase (NOS) activity was measured by monitoring the conversion of [3H]
      arginine to [3H]-citrulline. Immunohistochemical studies were performed. RESULTS:
      The NO-donor SIN-1 reduced in a concentration-dependent manner the frequency of
      contractions, whereas NO completely interrupted the contractile activity. In
      precontracted strips exposed to SIN-1 or NO, there were 6- and 12-fold increases
      of the cyclic GMP levels in comparison with control preparations. Activity of NOS
      was moderate. Overall innervation of the ureter was sparse, and there were few
      NOS-immunoreactive nerves. CONCLUSION: Although few NOS-containing nerves were
      found, pathways regulating the cyclic GMP levels of pig ureteral smooth muscle
      were demonstrated. Such pathways may be important targets for drugs producing
      relaxation of the mammalian ureter.

PMID- 8558722
TI  - Urodynamic effects of intravesical oxybutynin chloride in conscious rats.
AB  - PURPOSE: To examine the factors of intravesical oxybutynin influencing the
      cystometrogram in normal conscious rats at various pH levels and concentrations
      of oxybutynin. MATERIALS AND METHODS: A cystostomy catheter was implanted into
      the bladders of male Sprague-Dawley rats. We compared the urodynamic effects of
      intravesical oxybutynin dissolved in pH 4.44, 6.44 and 8.44 buffer. Two
      concentrations of oxybutynin solution were adopted, 0.06 and 0.6 mg./ml., and
      were dissolved in each pH buffer. RESULTS: Although a 26% increase in bladder
      capacity was recognized 1 hour after instillation of pH 8.44, 0.06 mg./ml.
      oxybutynin, no significant difference was found in comparison with control rats.
      At the concentration of 0.6 mg./ml., bladder capacity markedly decreased 30
      minutes to 1 hour after instillation even at pH 6.44 and 8.44. Significant
      decreases in detrusor contraction pressure were recognized 30 minutes to 1 hour
      after instillation. However, there were no significant differences among the 3 pH
      oxybutynin solutions. Compared with preinstillation values, significant increases
      in residual urine rates were observed in all pH oxybutynin solutions.
      Furthermore, the residual urine rate after instillation of pH 8.44 oxybutynin
      solution differed significantly from that of pH 4.44 oxybutynin. CONCLUSION: Our
      results demonstrate that pH and concentration of intravesical oxybutynin solution
      may play an important role in relaxation of the bladder. A high concentration of
      oxybutynin is considered irritating to the bladder mucosa.

PMID- 8558723
TI  - Altered contractility of rabbit penile corpus cavernosum smooth muscle by
      hypoxia.
AB  - PURPOSE: To investigate the effects of severe hypoxia on trabecular smooth muscle
      contractility. MATERIALS AND METHODS: Strips of rabbit corpus cavernosum were
      mounted in organ chambers to measure isometric tension. In some experiments
      intracellular free Ca2+ concentration and tension were measured by the
      intracellular fluorescent dye FURA-2 and isometric tension recording
      simultaneously. RESULTS: Contractions elicited by norepinephrine, endothelin-1 or
      potassium were attenuated under hypoxic conditions (pO2 approximately 10 mm. Hg).
      Strips contracted with 20 mM. K+ under normoxic conditions and then exposed to
      hypoxia consistently lost the potassium-induced tone. The hypoxia-induced
      relaxation was not affected by the removal of the endothelium, by treatment with
      the cyclooxygenase blocker, indomethacin, or with the guanylate cyclase blocker,
      methylene blue. The potassium channel opener, cromakalim, and adenosine relaxed
      potassium contracted strips; however, the potassium channel blockers
      glibenclamide, apamin, barium chloride and charybdotoxin or the adenosine
      receptor antagonist 8-(p-sulfonyl)theophylline were unable to prevent hypoxia
      induced relaxation. Tetraethylammonium, a potassium channel blocker, and the
      depolarizing agents ouabain and high potassium (80 mM.), partially prevented
      hypoxia-induced relaxation. The calcium ionophore, ionomycin, had no effect on
      hypoxia-induced relaxations. Hypoxia, within 2 to 6 minutes, caused a large
      accumulation in intracellular calcium, concomitant with a loss of trabecular
      smooth muscle tone. Both these effects could be reproduced by inhibiting
      oxidative phosphorylation with 2,4,dinitrophenol. Reoxygenation resulted in an
      immediate recovery of both tone and intracellular calcium levels. Tissues under
      hypoxic conditions for 30 minutes had a 24% and 67% decrease in the ATP/ADP ratio
      and in creatine phosphate concentrations, respectively. CONCLUSION: Hypoxia
      causes a simultaneous increase in intracellular calcium and relaxation which, we
      propose, is the consequence of inhibition of oxidative phosphorylation with loss
      of high energy phosphates, necessary for the homeostasis of Ca2+ and the
      contractile mechanism of the cavernosal smooth muscle.

PMID- 8558724
TI  - Veno-occlusive dysfunction of corpora cavernosa: comparison of diagnostic
      methods.

PMID- 8558725
TI  - Exercise training improves functional status in patients with peripheral arterial
      disease.
AB  - PURPOSE: In patients with intermittent claudication (IC) a structured walking
      exercise program improves exercise performance. However, few studies have
      evaluated the effects of exercise training on functional status during daily
      activities. We hypothesized that a supervised exercise training program would
      improve functional status in patients with IC, with 24 weeks of training more
      beneficial than 12 weeks. A secondary aim was to evaluate the effects of strength
      training and combinations of strength and treadmill training on functional
      status. METHODS: Twenty-nine men with disabling IC were randomized to 12 weeks of
      either supervised treadmill training (3 hr/wk at a work intensity sufficient to
      produce claudication), strength training (3 hr/wk of resistive training of six
      muscle groups of each leg), or to a nonexercising control group. Functional
      status was assessed by questionnaires characterizing walking ability (Walking
      Impairment Questionnaire, WIQ), habitual physical activity level (Physical
      Activity Recall, PAR), and physical, social, and role functioning, well-being,
      and overall health (Medical Outcomes Study SF-20, MOS). Patients alos had their
      activity levels monitored with an activity monitor (Vitalog). RESULTS: After 12
      weeks of treadmill training PAR scores increased by 48 metabolic equivalent
      hr/wk, the MOS physical functioning score by 24 percentage points, and the number
      of bouts of walking activity measured by the Vitalog by 4.5 bouts/hr (all p <
      0.05). No changes were seen in WIQ scores. After 12 additional weeks of treadmill
      training improvements initially observed in the PAR, MOS, and Vitalog scores were
      maintained, and in addition the ability to walk distances (WIQ) improved by 31
      percentage points, and the IC severity score had improved by 29 percentage points
      (both p < 0.05). After 12 weeks of strength training patients improved their WIQ
      walking speed, stair climbing scores, and MOS well-being scores with no other
      changes in functional status. Subjects in the control group did not improve
      functional status by any measure. Twelve weeks of treadmill training after the
      strength training program maintained WIQ walking speed scores, and activity level
      defined by Vitalog improved. Twelve weeks of combined treadmill and strength
      training after the control period had no effect on functional status.
      CONCLUSIONS: A supervised treadmill training program improved functional status
      during daily activities, with 24 weeks more effective than 12. In addition,
      treadmill training alone was more effective in improving functional status in
      patients with IC than strength training or combinations of the training
      modalities.

PMID- 8558726
TI  - The correlation of ankle oscillometric blood pressures and segmental pulse
      volumes to Doppler systolic pressures in arterial occlusive disease.
AB  - PURPOSE: This study was designed to evaluate the accuracy and failure rates of
      automatically collected oscillometric ankle systolic pressures (Psys) and pulse
      volumes (Pvol) using a new algorithm as compared with Psys obtained by standard
      manual Doppler-and-cuff technique. METHODS: One hundred ten consecutive patients
      at a vascular laboratory had brachial and ankle Psys measured with the two
      methods. Pvol at or near the mean arterial pressure was also obtained
      automatically by the oscillometric device. RESULTS: Both methods showed a 6.6%
      failure rate when measuring Psys at the ankle. Oscillometric Psys measurement was
      possible when Doppler Psys failed as a result of nonoccluding arteries. No
      difference was found between the two methods in occluding limbs with ankle
      brachial indexes of 1.30 or more. Sequential brachial Psys values had a mean
      difference (Doppler-oscillometric) or 2 +/- 10.9 mm Hg and a correlation
      coefficient (r) of 0.92. Measurements at the ankle had a mean difference of -8.4
      +/- 16.8 mm Hg and r = 0.90. These differences were not statistically
      significant. Mean arterial pressure Pvol recorded at the ankle also correlated
      with ankle Doppler Psys (r = 0.71) and showed a 1.9% failure rate. CONCLUSION:
      Both automatic oscillometric plethysmographic Psys and Pvol at the ankle are
      shown to correlate well with Doppler-and-cuff Psys in patients with vascular
      disease. Oscillometric measurements can replace Doppler measurements in most
      clinical situations.

PMID- 8558727
TI  - Ruptured abdominal aortic aneurysms: who should be offered surgery?
AB  - PURPOSE: Operation for ruptured abdominal aortic aneurysm is generally still
      associated with a high mortality rate. A review of our experience over a 9-year
      period was undertaken to identify factors present on admission associated with 30
      day operative mortality. METHODS: A retrospective analysis of 154 patients with
      ruptured abdominal aortic aneurysm submitted for operation in a university
      teaching hospital between January 1985 and December 1993 was undertaken. RESULTS:
      The hospital mortality rate was 39%. Logistic regression identified a set of five
      independent preoperative factors associated with mortality: age (> 76 years),
      creatinine level (> 0.19 mmol/L), loss of consciousness after arrival, Hb (< 9
      g%), and electrocardiographic ischemia. In the 52 patients with a single risk
      factor present, the mortality rate was 37%, with two factors (32 patients) it was
      72%, with three or more factors (8 patients), it was 100%, and no patient had all
      five risk factors. A 16% mortality rate was found in the 62 patients with no risk
      factors. CONCLUSION: These risk factors can be easily determined on admission and
      may be used to help improve patient selection for surgical intervention. The
      current operative mortality rate for ruptured abdominal aortic aneurysm remains
      high, and in some cases health care resources are used in a nonproductive
      fashion. Restricted patient selection and allocation of scarce resources will
      bring advantages to both the patient and the community.

PMID- 8558728
TI  - Results of a policy with arm veins used as the first alternative to an
      unavailable ipsilateral greater saphenous vein for infrainguinal bypass.
AB  - PURPOSE: Aggressive policies for distal bypass and coronary revascularization
      increase the need to identify alternatives to autologous saphenous vein grafts.
      We examined the performance of arm vein as the primary alternative to
      contralateral saphenous vein when the ipsilateral saphenous vein was not
      available. METHODS: A total of 250 arm vein grafts were studied retrospectively
      in 224 patients (143 men, 81 women, 82.6% with diabetes, mean age 68.3 years)
      from February 1989 to April 1994. Intraoperative angioscopy was carried out to
      observe valve lysis, remove abnormalities, and select optimal vein segments.
      RESULTS: A total of 85 primary, 103 repeat, and 62 graft revision procedures were
      done for limb salvage in 99.2% of the patients. A total of 41 femoropopliteal,
      114 femorotibial-pedal, 33 popliteodistal, and 62 jump or interposition grafts
      were constructed. A total of 199 grafts were single vein, and 51 were composite
      vein. The source was cephalic vein alone in 50.4%, cephalic and basilic vein in
      35.6%, and basilic vein only in 14%. The contralateral saphenous vein as an
      alternative conduit was available in 97 (38.8%) instances. Interventions guided
      by angioscopy to "upgrade" the graft were necessary in 51.6%. Overall early
      patency (< or = 30 days) was 94.8% (n = 13 occlusions). The cumulative primary
      patency rate at 1 year was 70.6%, the secondary patency rate was 76.9%, and the
      limb salvage rate was 88.2%. The 3-year patency rate (limb salvage) was 51.9%
      (92.4%) for primary grafts, 56.7% (67.1%) in revision grafts, and 42.4% (79.9%)
      in repeat grafts. In 22.7% (22 of 97) the available contralateral saphenous vein
      was used for distal revascularization within the follow-up period. CONCLUSIONS:
      Arm veins are an easily accessible autologous conduit of sufficient length to
      reach the midtibial level. Excellent patency rates allow durable limb salvage in
      otherwise difficult circumstances. Vein configuration and splicing do not affect
      patency rates, but vein quality and repeat operations do. Angioscopy is a
      valuable adjunct to upgrade graft quality. The contralateral saphenous should be
      saved for subsequent contralateral revascularization or coronary artery bypass
      grafting.

PMID- 8558729
TI  - Congenitally absent inferior vena cava presenting in adulthood with venous stasis
      and ulceration: a surgically treated case.
AB  - Absence of the inferior vena cava (IVC) is an uncommon congenital abnormality.
      Symptoms of lower extremity venous insufficiency resulting from this anatomic
      abnormality have been reported only once in the English literature, and no
      experience with surgical treatment of this condition has been published. We
      report the case of an otherwise healthy 41-year-old man with an 18-month history
      of severe venous insufficiency involving the right leg manifested by extensive
      ulceration that did not respond to aggressive conservative treatment. Duplex
      findings were not suggestive of venous obstruction or reflux, but venography
      documented no filling of the common iliac vein or inferior vena cava, and outflow
      was via collaterals to the azygous and hemiazygous systems. Computed tomography
      demonstrated complete absence of the inferior vena cava with azygous
      continuation. A prosthetic bypass from the external iliac to the intrathoracic
      azygous vein was performed with complete symptomatic relief after a 30-month
      follow-up period. Venous bypass surgery may play a role in treatment of this rare
      cause of venous insufficiency.

PMID- 8558730
TI  - Intracerebral hemorrhage after carotid endarterectomy associated with ipsilateral
      fibrinoid necrosis: a consequence of the hyperperfusion syndrome?

PMID- 8558731
TI  - Deep venous thrombosis with pulmonary embolus after selective embolization of an
      internal iliac artery aneurysm.
AB  - A 69-year-old man with an isolated right internal iliac artery aneurysm measuring
      5.6 cm in diameter was treated with percutaneous embolization inducing thrombosis
      of the aneurysm. Four months later, he was seen with thrombosis of the right
      common iliac vein and pulmonary embolus. He subsequently underwent ligation of
      the aneurysm and repair of the right common iliac artery. Computed tomographic
      and operative findings suggested that the iliac vein thrombosis was the result of
      direct compression by the aneurysm itself, as well as perianeurysmal inflammation
      that encased the right common iliac vein. This report summarizes this case and
      presents a new potential long-term complication after successful selective
      embolization of an internal iliac artery aneurysm.

PMID- 8558732
TI  - Intravascular stenting of traumatic abdominal aortic dissection.
AB  - PURPOSE: We describe the case of a 34-year-old man with blunt abdominal trauma.
      Initial abdominal computed tomography scan showed retroperitoneal hematoma,
      pancreatic contusion, multiple fractures of the transverse process in the thoraco
      lumbar spine, and infrarenal aortic dissection. METHOD: Angiography revealed that
      the aortic dissection originated proximal to the inferior mesenteric artery and
      extended down to the left common iliac artery without vascular obliteration. The
      pancreatic trauma was managed without operation, and the dissection was treated
      with aortic and left iliac endovascular self-expanding Schneider Wall Stents.
      RESULT: Immediate angiographic and computed tomography scan examination showed
      the obliteration of the greater part of the dissection with persistence of a
      short dissected segment at the level of the aortic bifurcation. Examination a
      week later showed thrombosis of this false lumen and complete obliteration of the
      dissection. CONCLUSION: Intravascular stenting allowed treatment of the
      dissection without open surgical procedures requiring laparotomy and aortic
      operation.

PMID- 8558733
TI  - Infected iliac pseudoaneurysm after uncomplicated percutaneous balloon
      angioplasty and (Palmaz) stent insertion: a case report and literature review.
AB  - Percutaneous balloon angioplasty and endovascular stent placement are becoming
      common techniques intended to reduce the need for surgical bypass procedures that
      may be more expensive or have higher morbidity rates. Prophylactic antibiotics
      are not currently used before stent placement in most centers even when implanted
      via the femoral route. Infectious complications have been rare. In the case
      presented here an infected common iliac pseudoaneurysm occurred after
      percutaneous balloon angioplasty and stent placement. The literature is reviewed.

PMID- 8558734
TI  - A personal view: the Asymptomatic Carotid Atherosclerosis Study results--read the
      label carefully.

PMID- 8558735
TI  - Vascular surgery in the United States: workforce issues. Report of the Society
      for Vascular Surgery and the International Society for Cardiovascular Surgery,
      North American Chapter, Committee on Workforce Issues.
AB  - The Committee on Workforce Issues of the Society for Vascular Surgery (SVS) and
      the North American Chapter, International Society for Cardiovascular Surgery (NA
      ISCVS) generated data on the numbers and trends of operations performed and
      workforce requirements to provide surgical care of patients with vascular
      disease. Data for analysis were obtained from The National Center for Health
      Statistics-National Hospital Discharge Survey and questionnaires sent to 2732
      vascular surgeons. The data showed that SVS/NA-ISCVS and regional vascular
      society (RVS) surgeons performed 51% of 583,000 vascular procedures undertaken in
      the United States in 1992. This represents a 24% increase over the 41% reported
      in 1985 by similarly defined surgeons. Analysis of 1992 index cases documented
      that SVS/NA-ISCVS and RVS surgeons accounted for 80% of 31,000 aortoiliofemoral
      bypasses, 68% of 46,000 aortic aneurysmectomies, 64% of 91,000 carotid
      endarterectomies, and 72% of 98,000 angioaccess procedures. The mean numbers of
      vascular operations performed in 1992 by SVS/NA-ISCVS and RVS surgeons were 144
      and 100, respectively. These procedures represented 64% and 39% of the total
      surgical caseload of SVS/NA-ISCVS and RVS surgeons, respectively. American Board
      of Surgery (ABS)-certified vascular surgeons performed a mean of 171 vascular
      operations in 1992. Other surgeons, including ABS-certified general surgeons,
      appear to be performing fewer vascular operations. The latter fact and the
      increasing incidence of vascular disease in an expanding elderly population
      supports a continued need for vascular surgery specialists. Evolving technology
      and new health care delivery systems, however, may lessen the need for surgical
      care of these patients. Continued assessments of workforce activity will allow
      better definition of changing vascular surgery needs.

PMID- 8558736
TI  - Ongoing vascular laboratory surveillance is essential to maximize long-term in
      situ saphenous vein bypass patency.
AB  - PURPOSE: The purpose of this study was to assess the contribution of ongoing
      graft surveillance to maximize long-term patency of lower limb in situ saphenous
      vein bypasses. METHODS: From January 1981 to October 1994, 556 autogenous grafts
      were constructed in 499 patients. The distal anastomosis was at the popliteal
      level in 207 (37%) and the tibial level in 349 (63%). All patients were enrolled
      in a prospective surveillance protocol to identify lesions that compromise graft
      patency and were evaluated at 1 day, 1 week, 6 weeks, and 3 months. Surveillance
      studies were then obtained every 3 months for the first 2 postoperative years and
      every 6 months thereafter. RESULTS: Four-hundred-fifty abnormalities were
      detected in 236 grafts. The median interval from the initial procedure to
      detection of an abnormality was 12 months (range 0 to 113 months) and varied with
      the location of the defect. Later in the life of the graft, progression of
      atherosclerotic disease manifested as inflow obstruction at a median of 15
      months, and outflow disease threatened the graft at a median of 29 months (r =
      0.0003). Of the 450 surveillance abnormalities, 294 (65%) occurred within the
      first 2 years after operation, and 156 (35%) developed more than 2 years after
      operation. Of the 236 grafts that developed surveillance abnormalities, 50 (21%)
      developed the initial defect more than 2 years after the initial bypass
      procedure. Eleven percent of grafts remaining free of abnormality after 2 years
      went on to fail. Sixty-seven interventions were performed on 62 extremities after
      24 months, with 30 involving previously unrevised grafts. CONCLUSIONS: Because
      lesions amenable to revision continue to develop years after vein bypass
      construction, perpetual surveillance is required to ensure optimal rates of graft
      patency.

PMID- 8558737
TI  - Regarding "What you didn't know about the NASCET". North American Symptomatic
      Carotid Endarterectomy Trial.

PMID- 8558738
TI  - Regarding "What you didn't know about the NASCET". North American Symptomatic
      Carotid Endarterectomy Trial.

PMID- 8558739
TI  - Ultrasound-guided compression closure of postcatheterization pseudoaneurysms
      during concurrent anticoagulation: a review of seventy-seven patients.
AB  - PURPOSE: Data from our institution and elsewhere have demonstrated that
      ultrasound-guided compression closure (UGCC) is an effective method of treating
      postcatheterization pseudoaneurysms. Whereas patients receiving anticoagulation
      do not have as high a success rate as those not receiving anticoagulants, there
      have been no large series evaluating the factors associated with success or
      failure in patients receiving anticoagulation. The purpose of this study is to
      determine whether uninterrupted anticoagulation interferes with successful UGCC
      of pseudoaneurysms and to identify factors associated with success or failure.
      METHODS: From May 1991 to September 1994, 238 cases of attempted UGCC of
      pseudoaneurysms were performed in our vascular laboratory. Only patients who
      received uninterrupted heparin, warfarin, or both at the time of pseudoaneurysm
      compression were eligible for inclusion into the study. Seventy-seven patients
      were identified who met the study criteria. RESULTS: Successful pseudoaneurysm
      compression was obtained in 56 (73%) patients, whereas 21 (27%) patients had a
      failed UGCC. In the successfully treated group, seven (12.5%) required between
      two to three compression attempts to induce sustained thrombosis. There was no
      statistical difference in age, sex, sheath size, days after procedure, location
      of pseudoaneurysm, or number of chambers in the pseudoaneurysm between those
      patients who had a successful repair and those who did not. If the pseudoaneurysm
      was less than 4 cm in diameter, 51 of 65 patients (78%) had a successful repair
      compared with 5 of 12 patients (42%) with a pseudoaneurysm of 4 cm or greater (p
      = 0.013). There was no statistical difference between success and failure in
      patients receiving warfarin alone (3.73 mean international normalized ratio, 72%
      success rate), heparin alone (mean activated partial thromboplastin time of 63
      seconds, 92% success rate), or heparin and warfarin (mean activated partial
      thromboplastin time of 70 seconds, mean international normalized ratio of 4,
      success rate of 67%). No arterial or venous thrombosis occurred during
      pseudoaneurysm compression. CONCLUSION: Successful UGCC of pseudoaneurysms
      occurred in a large percentage of patients receiving full-dose, uninterrupted
      anticoagulation. The only factor influencing success was the size of the
      pseudoaneurysm.

PMID- 8558740
TI  - A prospective evaluation of atherosclerotic risk factors and hypercoagulability
      in young adults with premature lower extremity atherosclerosis.
AB  - PURPOSE: Fifty-one consecutive patients with premature lower extremity
      atherosclerosis were prospectively evaluated for atherogenic risk factors and
      primary or acquired hypercoagulability, which might contribute to early ischemia
      and revascularization failure. METHODS: Laboratory tests included plasma assays
      of (1) natural anticoagulants (NAC), lipoprotein (a) (Lp[a]), and anticardiolipin
      antibodies, and (2) fibrinolytic activators and inhibitors at baseline and
      stimulated after 20 minutes of upper extremity venous occlusion. RESULTS: Forty
      six (90%) of these 51 patients had laboratory abnormalities. One or more NAC
      deficiencies were found in 15 (30%) patients and included antithrombin III (n =
      5), protein C (n = 8), protein S (n = 4), and heparin cofactor II (n = 2).
      Hypofibrinolysis was identified as a deficiency of stimulated tissue plasminogen
      activator in 22 (45%) patients and elevated plasminogen activator inhibitor-1
      (PAI-1) in 29 (59%). Elevated Lp(a) was found in 43 (86%) patients. Five (10%)
      patients had anticardiolipin antibodies. Ten patients had combined NAC deficiency
      and hypofibrinolysis. Five (10%) patients had no abnormality. NAC deficiencies,
      especially protein C deficiency, were associated with acute ischemia (p < 0.01),
      prior vascular intervention (p < 0.01), an increasing number of total vascular
      procedures (p < 0.01), and major amputation (p < 0.01). PAI-1 was associated with
      a history of heart disease (p < 0.05) and prior vascular procedures (p < 0.05).
      Elevated Lp(a) was associated with elevated PAI-1 (p < 0.05). Retesting in 20
      patients suggested that 80% of NAC deficiencies were acquired, but abnormalities
      persisted in 66% of patients with elevated PAI-1 and in 93% of those with
      elevated Lp(a). CONCLUSIONS: These data strongly support the hypothesis that the
      convergence of atherogenic risk factors and hypercoagulability play an important
      role in early ischemia and poor results reported for lower extremity vascular
      procedures in young adults.

PMID- 8558741
TI  - Activated protein C resistance: prevalence and implications in peripheral
      vascular disease.
AB  - PURPOSE: Activated protein C (APC) is a naturally occurring anticoagulant that
      interacts with factors V and VIII to inhibit the clotting cascade. Resistance to
      APC (APC-R), hypothesized to occur as a result of an abnormal factor V, has been
      documented in up to 40% of patients with venous thrombotic events, but its
      prevalence in patients with arterial disease remains ill defined. METHODS: With
      an assay of APC resistance that expresses the ratio of the activated partial
      thromboplastin time with and without the addition of exogenous APC, APC
      resistance ratios were quantitated in 200 individuals comprising 177 patients
      with vascular disease and 23 control subjects. An abnormal activated partial
      thromboplastin time was present in four patients who were excluded from analysis.
      The 173 remaining patients formed the study population and were divided into
      diagnostic subgroups on the basis of the most symptomatic problem. RESULTS: APC
      resistance was documented in 20 individuals, representing 11.6% of the study
      group. The highest prevalence of APC resistance was observed in patients with
      lower extremity occlusive disease, with the APC-R ratio below 2.0 in 13.7%.
      Within the subgroup of individuals with lower extremity disease, 76 patients (10
      with APC-R, 13.2%) underwent infrainguinal bypass and were monitored a mean of 47
      +/- 8 months. Occlusion of the arterial reconstruction occurred in 22 patients
      (29%). Six (60%) of the patients with APC-R had failed reconstructions, versus 16
      (24%) of 66 patients without APC-R (p = 0.02). CONCLUSIONS: These findings
      suggest that APC-R is relatively common in patients with peripheral vascular
      disease, especially in those with lower extremity occlusive disease. APC-R
      appears to be a risk factor for failure of infrainguinal bypass. These
      observations suggest that screening for APC-R may be useful in patients with
      peripheral vascular disease, providing the opportunity to restore the normal
      thrombogenic balance with anticoagulant therapy in susceptible individuals.

PMID- 8558742
TI  - Vascular surgery--comparing outcomes.

PMID- 8558743
TI  - Lipoprotein (a), homocysteine, and hypercoagulable states in young men with
      premature peripheral atherosclerosis: a prospective, controlled analysis.
AB  - PURPOSE: Elevated lipoprotein (a) (Lp[a]) lipoprotein, total homocysteine, and
      hypercoagulable states (HCS) have all been implicated as risk factors for
      premature-onset atherosclerosis. This study was performed to determine the
      prevalence of these abnormalities in young men with chronic lower extremity
      ischemia (peripheral vascular disease [PVD]) and to determine their relative
      strengths as risk factors for premature peripheral atherosclerosis. METHODS: We
      analyzed 50 young white men (aged 45 years or younger at onset of symptoms) and
      compared them with 45 age-matched white male control subjects. RESULTS:
      Atherosclerotic risk factors were similar in both groups. The mean (+/- SEM)
      Lp(a) lipoprotein level was 36 +/- 6 mg/dl among the study patients, compared
      with 14 +/- 2 mg/dl among control subjects (p = 0.02, Mann-Whitney). Twenty (40%)
      study patients and seven (16%) control subjects had Lp(a) lipoprotein levels of
      30 mg/dl or greater (atherosclerotic risk threshold) (p = 0.01, odds ratio =
      3.62, confidence interval (CI) 1.4 to 9.5). Positive HCS panels (antiphospholipid
      antibodies or deficiencies in antithrombin III, protein C, or protein S) were
      nearly twice as prevalent in study patients (n = 15, 30%) as in controls (n = 8,
      18%), but this difference did not achieve statistical significance. The mean
      total plasma homocysteine level among the study patients was 15.9 +/- 0.9
      mumol/L, which was not significantly different from the mean control value of
      14.7 +/- 0.7 mumol/L. Lp(a) lipoprotein was related to risk of premature PVD
      through a linear logistic relationship (p = 0.003, odds ratio per each 1 mg/dl
      Lp(a) change was 1.03, CI 1.0 to 1.1). Multivariate analysis with stepwise
      logistic regression selected two variables: Lp(a) lipoprotein > or = 30 mg/dl (p
      = 0.01, odds ratio = 3.6, CI 1.3 to 9.9) and family history (p = 0.07, odds ratio
      = 2.2, CI 0.9 to 5.3). Tests of interaction demonstrated no effect between Lp(a)
      lipoprotein, HCS, and homocysteine. CONCLUSIONS: Lp(a) lipoprotein of 30 mg/dl or
      greater is an independent risk factor for premature peripheral atherosclerosis in
      men. None of the other examined variables exhibited a significant association
      with premature PVD.

PMID- 8558744
TI  - Thrombolysis or peripheral arterial surgery: phase I results. TOPAS
      Investigators.
AB  - PURPOSE: Thrombolytic therapy is widely used in the treatment of peripheral
      arterial occlusion, but prospective, randomized comparisons with standard therapy
      remain few. A multicenter trial of thrombolysis or peripheral arterial surgery
      (TOPAS) was organized to compare critically the use of recombinant urokinase
      (rUK) or surgery for the initial treatment of acute lower-extremity ischemia.
      Phase I of the trial was designed as a dose-ranging trial to evaluate the safety
      and efficacy of three doses of rUK in comparison with surgery. METHODS: In a
      multicenter, prospective, double-blind comparison, 213 patients who had acute
      lower-extremity ischemia for 14 days or fewer were randomized to one of two
      groups. The first group received one of three dosages of rUK (catheter-directed
      at 2000, 4000, or 6000 IU/min for 4 hours, then 2000 IU/min to a maximum of 48
      hours). The second group underwent surgery. Successful thrombolysis was followed
      by surgical or endovascular interventions when anatomic lesions responsible for
      the occlusion were unmasked. Patients were followed-up for 1 year; data were
      evaluated on an intent-to-treat basis. RESULTS: The 4000 IU/min rUK dosage was
      chosen as the most appropriate thrombolytic regimen because it maximized lytic
      efficacy against the risk of bleeding. Complete (> 95%) lysis of thrombus was
      achieved in 71% of the 49 patients who were randomized to the 4000 IU/min group,
      with a mean infusion time of 23 hours. In contrast, complete lysis was achieved
      in 67% of patients who received 2000 IU/min and in 60% of patients who received
      6000 IU/min. Hemorrhagic complications occurred in 2% of the 4000 IU/min group
      versus 13% of the 2000 IU/min group (p = 0.05) and 16% of the 6000 IU/min group
      (p = 0.03). In a comparison of the 4000 IU/min group with the surgical group, the
      1-year mortality rate (14% vs 16%) or amputation-free survival rate (75% vs 65%)
      did not differ significantly. The frequency and magnitude of surgery in the
      patients randomized to rUK were decreased (p < 0.001). CONCLUSION: The
      preliminary results suggest that an initial rUK dose of 4000 IU/min is safe and
      efficacious in the treatment of acute lower-extremity ischemia. rUK therapy is
      associated with limb salvage and patient survival rates similar to those achieved
      with surgery, concurrent with a reduced requirement for complex surgery after
      thrombolytic intervention.

PMID- 8558745
TI  - Long-term outcome of Raynaud's syndrome in a prospectively analyzed patient
      cohort.
AB  - PURPOSE: Knowledge of the long-term clinical outcome of Raynaud's syndrome (RS),
      essential both for patient counselling and formulation of optimal therapeutic
      recommendations, is conspicuously deficient in current medical literature. We
      have prospectively monitored 1039 patients with RS, 118 (11.4%) for more than 10
      years to determine whether initial characterization was able to predict outcome.
      METHODS: At initial presentation, patients were divided into four groups on the
      basis of vascular laboratory and serologic testing results: vasospastic,
      serologically positive (spast,sero+) and negative (spast,sero-) and obstructive,
      serologically positive (obst,sero+) and negative (obst,sero-). RESULTS:
      Connective tissue disease (CTD) was present initially in 48.6% of patients with
      spast,sero+ results and 72.9% of patients with obst,sero+ results. Of the
      remaining patients in these groups, progression to CTD during follow-up occurred
      in 16.4% of patients with spast,sero+ results and 30.4% of patients with
      obst,sero+ results. In the > 10-year follow-up group, progression to CTD occurred
      in 81.8% of patients in the obst,sero+ group. Progression to CTD occurred in 2.0%
      of patients in the spast,sero-group and 8.5% of patients in the obst,sero- group.
      Digital ulcers occurred in 15.5% of patients in the spast,sero+ group, 5.2% of
      patients in the spast,sero- group, 55.6% of patients in the obst,sero+ group, and
      48.2% of patients in the obst,sero- group. Digital or phalangeal amputations were
      required in 1.4%, 1.6%, 11.6%, and 19.0% of these patients, respectively.
      CONCLUSIONS: The long-term outcome of patients with RS can be predicted by
      initial serologic studies and separation into vasospastic and obstructive
      categories. Initial serologic positivity strongly predicts the development of
      CTD. Initial vascular laboratory classification of obstructive RS strongly
      predicts digital ulcerations, which occurred in half of these patients regardless
      of initial serologic study results. Amputations were required in 10% to 20% of
      patients with obstructive RS. These occurrences did not increase with increased
      duration of disease. Ulcerations and amputations were rare in patients initially
      with vasospastic RS.

PMID- 8558746
TI  - A clinical marker for arterial wall healing: the double line.
AB  - PURPOSE: B-mode imaging of a normal arterial wall shows two echo-dense lines
      separated by an echolucent zone. Immediately after carotid endarterectomy, this
      double-line pattern is no longer detectable, but it subsequently reappears in
      some patients. The objective of this study was to test the hypothesis that the
      postoperative double line is associated with a lower incidence of carotid
      restenosis. METHODS: Carotid arteries were serially studied with B-mode
      ultrasound imaging at 2 weeks and 1, 2, 3, 6, 9, 12, 18, and 24 months after
      carotid endarterectomy. The wall of the common carotid artery 1 to 2 cm distal to
      the proximal endarterectomized shelf was analyzed for the presence, quality, and
      thickness of double lines. All hemodynamically significant stenoses (> or = 50%
      diameter reducing) were documented with standard duplex scanning criteria.
      RESULTS: Twenty-four carotid arteries in 23 patients were studied for a mean of
      14.7 months (range, 3 to 24 months). A double line developed in 21 common carotid
      arteries (87.5%) at a mean time of 3.2 months (range, 0.5 to 9.0 months) after
      surgery with a mean thickness of 0.65 mm (SD = 0.17 mm) at the time of initial
      detection. A single hemodynamically significant stenosis developed in this group.
      All three of the remaining arteries that did not form the double-line pattern
      developed hemodynamically significant stenoses. Carotid restenosis was more
      likely to occur in arteries that did not form double lines (p < 0.05, Fisher's
      exact test). CONCLUSIONS: The majority of carotid arteries re-form a double line
      after endarterectomy. These arteries are less likely to develop restenotic
      lesions caused by myointimal hyperplasia.

PMID- 8558747
TI  - Endogenous reactive oxygen metabolites mediate sublethal endothelial cell
      dysfunction during reoxygenation.
AB  - PURPOSE: Endothelial cells (EC) secrete vasoactive eicosanoids, which maintain
      organ blood flow. Because EC are a major source of eicosanoids, we studied the
      effects of reoxygenation on EC prostacyclin production. METHODS: Bovine aortic EC
      cultures were exposed to 2 hours of normoxia, then 1 hour of hypoxia (PO2 = 10 +/
      3.5 mm Hg), followed by 1.5 hours of reoxygenation in either normal medium or
      medium plus either superoxide dismutase (SOD, 300 units/ml), catalase (1200
      units/ml), allopurinol (5.0 x 10(-4) mol/L), or dinitrophenol (10(-4) mol/L).
      RESULTS: Prostacyclin production decreased to 40% (p < 0.05) of basal
      prostacyclin production after 1 hour of hypoxia. EC reoxygenated with control
      medium recovered to 48% of basal prostacyclin production. EC reoxygenated in SOD
      resulted in recovery (p < 0.05) to 154% of basal prostacyclin production after 60
      minutes. Catalase treatment resulted in recovery to 105% (p < 0.05) of basal
      prostacyclin production within 30 minutes of reoxygenation. Allopurinol treatment
      resulted in 77% recovery (p < 0.05) of basal prostacyclin production only during
      30 minutes of reoxygenation. Dinitrophenol treatment resulted in significant (>
      or = 85%, p < 0.05) sustained recovery of basal prostacyclin production at 30,
      60, and 90 minutes of experimental reperfusion. CONCLUSIONS: The hypoxia-induced
      decrease in EC prostacyclin does not recover during reoxygenation. Catalase/SOD
      allowed return to baseline prostacyclin production during reoxygenation,
      implicating reactive oxygen metabolites as mediators of decreased eicosanoid
      biosynthesis. Recovery of prostacyclin production after 60 minutes reoxygenation
      with dinitrophenol but not allopurinol suggests a mitochondrial origin of the
      oxygen metabolites responsible for decreased prostacyclin biosynthesis.

PMID- 8558748
TI  - Quantitative assessment of daily physical activity levels in patients with
      chronic heart failure by measuring energy expenditure--effects of converting
      enzyme inhibitor therapy.
AB  - Although a major goal in the treatment of chronic heart failure is to improve
      daily physical activity levels, this has not been assessed quantitatively. An
      increased daily activity level may be reflected by an increase in daily energy
      expenditure. In the present study, measurements of energy expenditure with a
      commercially available ambulatory calorimeter were first validated using cardio
      pulmonary exercise tests in 5 normal volunteers. The energy expenditure measured
      by the calorimeter correlated well with that estimated from oxygen uptake (r =
      0.89). Subsequently, the daily energy expenditure was serially measured with the
      calorimeter during long-term administration of the converting enzyme inhibitor
      ramipril for 24 weeks in 8 patients with chronic heart failure. Changes in
      echocardiographic parameters and exercise capacity were also studied. Peak oxygen
      uptake and anaerobic threshold assessed with symptom-limited maximal bicycle
      exercise were significantly increased 12 weeks or more after the initiation of
      treatment (P < 0.01 and P < 0.01, respectively). Left ventricular fractional
      shortening substantially, but not significantly, increased during this period (P
      < 0.1). These results strongly suggest that an overall improvement in heart
      failure was achieved after long-term ramipril therapy. The energy expenditure
      during daily activities was also significantly increased after ramipril therapy
      for 24 weeks (P < 0.01). Thus, the daily energy expenditure increased with
      improvement of heart failure, probably reflecting an increase in daily activity
      levels. We conclude that calorimetric measurement of daily energy expenditure is
      a novel and simple technique for quantitative evaluation of the effect of therapy
      on daily physical activity levels in patients with chronic heart failure.

PMID- 8558749
TI  - Long-term follow-up of idiopathic ventricular arrhythmias in otherwise normal
      children.
AB  - Clinical characteristics and long-term prognosis of 163 children with ventricular
      arrhythmias without underlying heart diseases (78 with ventricular premature
      contractions (VPC group), 39 with ventricular couplets (CPLT group), and 46 with
      ventricular tachycardia (VT group)) were studied by Holter electrocardiographic
      monitoring (Holter ECG) and treadmill exercise testing. The age of the subjects
      at the initial examination was 8.9 +/- 3.4 years in the VPC group, 9.9 +/- 3.5
      years in CPLT group, and 9.4 +/- 3.1 years in the VT group. The duration of the
      follow-up was 71.7 +/- 32.1 months in the VPC group, 65.9 +/- 32.8 months in the
      CPLT group, and 84.0 +/- 31.9 months in the VT group. VPC's disappeared during
      the follow-up period in 22 (28%) of the 78 children in the VPC group. CPLT's
      disappeared in 15 (38%) and VPC's disappeared in 9 (23%) of the 39 children in
      the CPLT group. In the 46 children in the VT group, VT disappeared in 30 (65%),
      and VPC's disappeared in 17 (37%). One child (2%) in the VT group died of heart
      failure due to drug-resistant sustained VT. The mean time until the disappearance
      of VPC's in the 163 patients was estimated to be 115.2 +/- 4.3 months. The mean
      time until the disappearance of VT in the 46 children in the VT group was
      estimated to be 89.0 +/- 4.9 months. Multivariate analysis of prognostic factors
      related to the disappearance of VPC's indicated that nighttime VPC's were
      significantly more likely to disappear (p = 0.018), and that symptomatic VT was
      significantly more likely to disappear than asymptomatic VT (p = 0.032), probably
      because more symptomatic cases received antiarrhythmic therapy. Ventricular
      arrhythmias in children without underlying diseases often disappeared, and the
      prognosis was generally favorable. However, appropriate treatment and follow-up
      were required in children with sustained VT, symptomatic VT, or VT with a high
      rate of VT.

PMID- 8558750
TI  - Effect of the initial bolus volume of recombinant tissue-type plasminogen
      activator on coronary recanalization and infarct size in Japanese acute
      myocardial infarction patients. Kumamoto University Myocardial Infarction Study
      (KUMIS) Group.
AB  - Coronary recanalization rate and infarct size were compared between 2 different
      methods of intravenously administering recombinant tissue-type plasminogen
      activator (rt-PA) 41.4 mg; 1) an initial bolus dose of 30% followed by infusion
      of the remainder over 60 min (30% group), and an initial bolus dose of 10%
      followed by infusion of the remainder over 60 min (10% group). Thirty min after
      beginning rt-PA infusion, the coronary recanalization rate was higher in the 30%
      group than in the 10% group (82.9% (34/41) vs 53.7% (22/41), p < 0.01). The peak
      creatine kinase and peak creatine kinase-MB levels were lower in the 30% group
      than in the 10% group. We conclude that a higher initial bolus dose of rt-PA
      gives a higher rate of recanalization of the infarct-related artery at the very
      early phase, and probably leads to a smaller infarct size.

PMID- 8558751
TI  - Role of collateral flow in a pharmacological stress test (a combination of low
      dose dobutamine and a vasodilator) as a predictor of wall motion reversibility.
AB  - The role of collateral flow was evaluated in a pharmacological stress test [a
      combination of low-dose dobutamine (DOB) and a vasodilator] as a predictor of
      wall motion reversibility at rest after percutaneous transluminal coronary
      angioplasty (PTCA) using ultrafast computed tomography (UFCT). Segments with wall
      motion abnormalities before PTCA were divided into two groups; ie, either with or
      without collateral flow. Patients were scanned at rest for baseline and again
      after 5 min of intravenous administration of 4 micrograms/kg per min of DOB after
      nitroglycerin (0.3 mg sublingually) or isosorbide dinitrate (2.5 mg bolus
      intravenous injection). Three months after PTCA, patients were scanned again and
      wall motion was compared with the previous findings. In collateral-dependent
      segments, the sensitivity of the pharmacological stress test as a predictor of
      wall motion reversibility was 87.5% and the specificity was 83.3%. In collateral
      independent segments, the sensitivity was only 41.7%, while the specificity was
      95.2%. Our findings demonstrate that the pharmacological stress test we used
      satisfactorily predicted wall motion reversibility in collateral-dependent
      segments, but tended to underestimate wall motion reversibility in collateral
      independent segments. Therefore, collateral flow may be an important factor in
      accurately predicting wall motion reversibility by this pharmacological stress
      test.

PMID- 8558752
TI  - Altered platelet alpha 2-adrenoceptors in patients with ischemic heart disease.
AB  - We evaluated the characteristics of platelet alpha 2-adrenoceptors in 12 patients
      with effort angina pectoris, 11 patients with variant angina pectoris and 11
      normal control subjects. alpha 2-Adrenoceptors were quantified using a
      radioligand binding assay with radiolabelled rauwolscine, an alpha 2-selective
      antagonist. In addition, plasma norepinephrine concentrations were measured by
      high performance liquid chromatography. The mean value of the maximal number of
      binding sites (Bmax) in patients with effort angina (205.1 +/- 11.3 fmol/mg
      protein) was significantly lower than that in control subjects (293.0 +/- 10.2
      fmol/mg protein). Bmax did not differ between patients with variant angina (322.9
      +/- 45.4 fmol/mg protein) and control subjects. There was no significant
      difference in the dissociation constant (Kd) among the 3 groups. The plasma
      norepinephrine concentration tended to be higher in patients with effort angina
      or variant angina than in normal controls, but this difference was not
      statistically significant. In addition, studies in another group of young
      volunteers (n = 20) revealed a negative correlation (r = -0.50, p < 0.05) between
      the Bmax of 3H-rauwolscine binding to platelets and the percent change in the
      plasma norepinephrine concentration when subjects moved from the supine to the
      standing position. This suggests a functional correlation between platelet alpha
      2-adrenoceptors and those located at presynaptic sites. If platelet alpha 2
      adrenoceptors correlate with presynaptic alpha 2-adrenoceptors, the current
      findings of decreased alpha 2-adrenoceptor density in platelets from patients
      with effort angina could represent attenuated negative feedback of norepinephrine
      by presynaptic alpha 2-adrenoceptors.

PMID- 8558753
TI  - Hemodynamic profiles during concurrent intraaortic balloon pumping and
      venoarterial bypass--a canine study comparing subclavian and femoral artery
      perfusion sites.
AB  - Concomitant use of venoarterial bypass (VAB) with centrifugal pump and
      intraaortic balloon pumping (IABP) is a common technique for cardiopulmonary
      resuscitation. This experimental study examines whether coronary perfusion and
      hemodynamics are affected by the site of the blood supply, comparing the
      subclavian artery and the femoral artery. VAB and IABP were performed in 11
      mongrel dogs with cardiopulmonary failure induced by acute myocardial infarction
      and hypoventilation. Aortic root pressure (AP), left atrial pressure, central
      venous pressure and coronary sinus blood flow (CSF) were measured, and blood gas
      analysis was performed. Subclavian artery perfusion (SAP) and femoral artery
      perfusion (FAP) were compared at bypass ratios of 25, 50, 75, 85, 100%. At bypass
      ratios of 75% and 85% the mean systolic AP was higher with SAP than with FAP. The
      mean diastolic AP was higher with SAP than with FAP at a bypass ratio of 50% or
      higher. CSF was higher with SAP than with FAP at a bypass ratio of 50% or higher.
      The coronary arteriovenous O2 content difference was lower with SAP than with FAP
      at a bypass ratio of 85% or higher. In conclusion, at a high bypass ratio, SAP
      was more effective than FAP in achieving diastolic augmentation, thus enhancing
      myocardial oxygen balance, even though SAP had less of a systolic unloading
      effect. These data support the use of SAP over FAP in patients with severe
      cardiopulmonary dysfunction requiring high-flow bypass, and especially in
      patients with myocardial ischemia.

PMID- 8558754
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from urinary tract infections (1992). I. Susceptibility
      distribution].
AB  - The frequencies of isolation and susceptibilities to antimicrobial agents were
      investigated on 732 bacterial strains isolated from patients with urinary tract
      infections in 11 hospitals during the period of June 1992 to May 1993. Of the
      above total bacterial isolates, Gram-positive bacteria accounted for 35.4% and a
      majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for
      64.6% and most of them were Escherichia coli. 1. Enterococcus faecalis Ampicillin
      (ABPC), imipenem (IPM) and vancomycin (VCM) showed the highest activities against
      E. faecalis isolated from patients with urinary tract infections. The MIC90S of
      them were 2 micrograms/ml. Piperacillin (PIPC) was also active with the MIC90 of
      8 micrograms/ml. The others except chloramphenicol (CP) were not so active with
      the MIC90S of 32 micrograms/ml or above. 2. Staphylococcus aureus including MRSA
      VCM showed the highest activities against S. aureus isolated from patients with
      urinary tract infections. Its MIC90 was 1 microgram/ml. Arbekacin (ABK) was also
      active with the MIC90 of 2 micrograms/ml. The others were not so active with the
      MIC90S of 32 micrograms/ml or above. 3. Staphylococcus epidermidis ABK showed the
      highest activities against S. epidermidis isolated from patients with urinary
      tract infections. Its MIC90 was 0.5 microgram/ml. Cefotiam (CTM) and VCM were
      also active with the MIC90S of 2 micrograms/ml. Penicillins except ABPC,
      gentamicin (GM), clindamycin (CLDM) and quinolones were not so active with the
      MIC90S of 64 micrograms/ml or above. 4. Streptococcus agalactiae Most of the
      agents were active against S. agalactiae isolated from patients with urinary
      tract infections. Penicillins, cephems, erythromycin (EM), and CLDM showed the
      highest activities. The MIC90S of them were 0.25 microgram/ml or below. Amikacin
      (AMK) and minocycline (MINO) were not so active with the MIC90S of 32
      micrograms/ml or above. 5. Citrobacter freundii IPM showed the highest activities
      against C. freundii isolated from patients with urinary tract infections. Its
      MIC90 was 1 microgram/ml. Cefozopran (CZOP) and amikacin (AMK) were also active
      with the MIC90S of 4 micrograms/ml. Penicillins and cephems generally were not so
      active. 6. Enterobacter cloacae IPM and GM showed the highest activities against
      E. cloacae. The MIC90S of them were 0.5 microgram/ml. Ciprofloxacin (CPFX) and
      tosufloxacin (TFLX) were also active with the MIC90S of 4 micrograms/ml.
      Penicillins and cephems generally showed lower activities. 7. Escherichia coli
      Most of the agents were active against E. coli. Flomoxef (FMOX), cefmenoxime
      (CMX), CZOP, IPM, carumonam (CRMN), norfloxacin (NFLX), ofloxacin (OFLX), CPFX
      and TFLX showed the highest activities against E. coli. The MIC90S of them were
      0.125 microgram/ml or below. Cefotiam (CTM), ceftazidime (CAZ), cefuzonam (CZON)
      and latamoxef (LMOX) were also active with the MIC90S of 0.25 microgram/ml.
      Penicillins were not so active with the MIC90S of 32 micrograms/ml or above. 8.
      Klebsiella pneumoniae Most of the agents were active against K. pneumoniae. FMOX,
      CMX, CZOP and CRMN showed the highest activities. The MIC90S of them were 0.125
      microgram/ml or below. But ampicillin (ABPC) was not so active with the MIC90 of
      128 micrograms/ml. 9. Proteus mirabilis Most of the agents were active against P.
      mirabilis. FMOX, CMX, CAZ, CZON, LMOX, CFIX, CPDX, CRMN, NFLX, CPFX and TFLX
      showed the highest activities against P. mirabilis isolated from patients with
      urinary tract infections. The MIC90S of them were 0.125 microgram/ml or below.
      ABPC and MINO were not so active with the MIC90S of 256 micrograms/ml or above.
      10. Pseudomonas aeruginosa Most of the agents were not so active against P.
      aeruginosa. IPM showed MIC90 of 8 micrograms/ml. Cefclidin (CFCL) and AMK showed
      MIC90S o

PMID- 8558755
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from urinary tract infections (1992). II. Background of
      patients].
AB  - Clinical background was investigated on 913 bacterial strains isolated from
      patients with urinary tract infections (UTIs) in 11 hospitals during the period
      from June, 1992 to May, 1993. 1. Distribution of sex, age and infections Among
      over forties males, the majority was taken by complicated urinary tract
      infections. Among females, the uncomplicated urinary tract infections was most
      frequent without a relation of age. 2. Distribution of sex, age and pathogens
      isolated from UTIs IN uncomplicated UTIs, Escherichia coli was most frequently
      isolated without a relation of age, and next CNS in under fifties. In complicated
      UTIs without indwelling catheter, E. coli and Enterococcus faecalis were isolated
      with a frequency of 12-28%, respectively. In complicated UTIs with indwelling
      catheter, Pseudomonas aeruginosa were most frequently isolated, and next E.
      faecalis. 3. Administration of antibiotics and pathogens isolated from UTIs In
      uncomplicated UTIs, pathogens, after administration of antibiotics, isolated from
      patients have obviously decreased from 306 to 44 isolates. And also, pathogens of
      complicated UTIs without indwelling catheter, have decreased from 217 to 76
      isolates. However, in complicated UTIs with indwelling catheter, pathogens after
      or before administration of antibiotics, were not revealed an obvious change. 4.
      Pathogens and UTIs with or without factor and operation In uncomplicated UTIs
      with or without factor and operation, E. coli was mainly detected. In complicated
      UTIs without indwelling catheter and with or without factor and operation, E.
      coli was mainly detected. In complicated UTIs with indwelling catheter and with
      factor and operation, P. aeruginosa and E. faecalis were detected, 19.6% and
      16.0%, respectively. Without factor and operation, P. aeruginosa was detected,
      28.9%, and next E. faecalis 13.3%. The distribution of pathogens after
      administration of antibiotics was similar.

PMID- 8558756
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from urinary tract infections (1992). III. Secular changes in
      susceptibility].
AB  - Susceptibilities of Enterococcus faecalis, Staphylococcus aureus, Citrobacter
      spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis,
      Pseudomonas aeruginosa and Serratia spp. isolated from patients with urinary
      tract infections (UTIs) in 11 hospitals during June 1992 to May 1993 to various
      antimicrobial agents were compared with those in the same period of previous
      years according to a classification, uncomplicated UTIs, complicated UTIs without
      indwelling catheter, and complicated UTIs with indwelling catheter. The
      susceptibilities of E. faecalis isolated from uncomplicated UTIs to quinolones
      has decreased. As for S. aureus, Citrobacter spp., Enterobacter spp., P.
      mirabilis and Serratia spp., which were detected very few in 1989, 1990, 1991 and
      1992, their susceptibilities were not observed an obvious change. E. coli, all
      strains were highly susceptibilities to latamoxef and cefozopran. And the
      susceptibilities of E. coli isolated from uncomplicated UTIs and complicated UTIs
      without indwelling catheter to minocycline has decreased in 1991, but they has
      been indicated a trend of recovery in 1992. The difference in according UTI's
      classification of the susceptibilities of Klebsiella spp. to minocycline in 1991
      has not recognized in 1992. And the susceptibilities of Klebsiella spp. isolated
      from complicated UTIs without indwelling catheter to quinolones has decreased.
      The susceptibilities of P. aeruginosa isolated from complicated UTIs to
      quinolones has been indicated a trend of recovery. These data should be
      considered in clinical treatment of various urinary tract infections.

PMID- 8558757
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from urinary tract infections (1993). I. Susceptibility
      distribution].
AB  - The frequencies of isolation and susceptibilities to antimicrobial agents were
      investigated on 657 bacterial strains isolated from patients with urinary tract
      infections in 10 hospitals during the period of June 1993 to May 1994. Of the
      above total bacterial isolates, Gram-positive bacteria accounted for 28.3% and a
      majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for
      71.7% and most of them were Escherichia coli. 1. Enterococcus faecalis Ampicillin
      (ABPC), imipenem (IPM) and vancomycin (VCM) showed the highest activities against
      E. faecalis isolated from patients with urinary tract infections. The MIC90s of
      them were 2 micrograms/ml. Piperacillin (PIPC) was also active with the MIC90 of
      8 micrograms/ml. The others were not so active with the MIC90s of 32
      micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM showed the
      highest activities against S. aureus isolated from patients with urinary tract
      infections. Its MIC90 was 1 microgram/ml. Arbekacin (ABK) was also active with
      the MIC90 of 2 micrograms/ml. The others were not so active with the MIC90s of 32
      micrograms/ml or above. 3. Staphylococcus epidermidis VCM showed the strongest
      activity against S. epidermidis isolated from patients with urinary tract
      infections. Its MIC90 was 1 microgram/ml. ABK was also active with the MIC90 of 4
      micrograms/ml. The others except ABPC were not so active with the MIC90s of 32
      micrograms/ml or above. 4. Streptococcus agalactiae Most of the agents were
      active against S. agalactiae isolated from patients with urinary tract
      infections. Penicillins, cephems, erythromycin (EM), and clindamycin (CLDM)
      showed the highest activities. The MIC90s of them were 0.25 microgram/ml or
      below. Amikacin (AMK) and minocycline (MINO) showed somewhat low activities with
      the MIC90s of 16 micrograms/ml. 5. Citrobacter freundii IPM showed the highest
      activities against C. freundii isolated from patients with urinary tract
      infections. Its MIC90 was 2 micrograms/ml. Cefozopran (CZOP) and gentamicin (GM)
      were also active with the MIC90s of 8 micrograms/ml. Penicillins and cephems
      generally were not so active. 6. Enterobacter cloacae IPM and GM showed the
      highest activities against E. cloacae. The MIC90s of them were 1 microgram/ml.
      CZOP and tosufloxacin (TFLX) were also active with the MIC90s of 8 micrograms/ml.
      Penicillins and cephems except CZOP showed lower activities with the MIC90s of 64
      micrograms/ml or above. 7. Escherichia coli Most of antimicrobial agents were
      active against E. coli. Flomoxef (FMOX), CZOP, IPM, CPFX and TFLX showed the
      highest activities against E. coli. The MIC90s of them were 0.125 microgram/ml or
      below. Cefmenoxime (CMX), ceftazidime (CAZ), cefuzonam (CZON), latamoxef (LMOX),
      carumonam (CRMN), norfloxacin (NFLX) and ofloxacin (OFLX) were also active with
      the MIC90s of 0.25 microgram/ml. Penicillins and MINO were not so active with the
      MIC90s of 32 micrograms/ml or above. 8. Klebsiella pneumoniae CZOP, IPM and CRMN
      showed the highest activities against K. pneumoniae. The MIC90s of them were
      0.125 microgram/ml or below. CAZ, CZON, CFIX, CPFX and TFLX were also active the
      MIC90s of 0.25 microgram/ml. Penicillins were not so active with the MIC90s of
      128 micrograms/ml or above. 9. Proteus mirabilis P. mirabilis was susceptible to
      a majority of drugs. CMX, CAZ, CZON, LMOX, CFIX, CRMN and CPFX showed the highest
      activities against P. mirabilis isolated from patients with urinary tract
      infections. The MIC90s of them were 0.125 microgram/ml or below. MINO was not so
      active with the MIC90 of 256 micrograms/ml or above. 10. Pseudomonas aeruginosa
      Most of the agents were not so active against P. aeruginosa. IPM showed MIC90 of
      8 micrograms/ml.

PMID- 8558758
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from urinary tract infections (1993). II. Background of
      patients].
AB  - Clinical background was investigated on 734 bacterial strains isolated from
      patients with urinary tract infections (UTIs) in 10 hospitals during the period
      from June, 1993 to May, 1994. 1. Distribution of sex, age and infections Among
      over fifties males, the majority was taken by complicated urinary tract
      infections. Among females, the uncomplicated urinary tract infections was most
      frequent without a relation of age. 2. Distribution of sex, age and pathogens
      isolated from UTIs In uncomplicated UTIs, Escherichia coli was most frequently
      isolated without a relation of age, and next Klebsiella spp. and CNS. In
      complicated UTIs without indwelling catheter, E. coli and Enterococcus faecalis
      were the most frequent. In complicated UTIs with indwelling catheter, Pseudomonas
      aeruginosa were most frequently isolated, and next E. faecalis. 3. The frequency
      of complexed infections in UTIs The frequency of complexed infections has
      increased from in uncomplicated UTIs to complicated UTIs. 4. Administration of
      antibiotics and pathogens isolated from UTIs In uncomplicated UTIs, pathogens,
      after administration of antibiotics, isolated from patients have obviously
      decreased from 222 to 33 isolates. And also, pathogens of complicated UTIs
      without indwelling catheter, have decreased from 205 to 50 isolates. However, in
      complicated UTIs with indwelling catheter, pathogens after or before
      administration of antibiotics, were not revealed an obvious change. 5. Pathogens
      and UTIs with or without factor and operation In uncomplicated UTIs with or
      without factor and operation, E. coli was mainly detected. In complicated UTIs
      without indwelling catheter and with or without factor and operation, E. coli and
      E. faecalis were mainly detected. In complicated UTIs with indwelling catheter
      and with factor and operation, P. aeruginosa and E. faecalis were mainly
      detected, 22.0% and 14.1%, respectively. Without factor and operation, was
      detected, E. faecalis 21.1%, and next Proteus spp. 15.8%. The distribution of
      pathogens, in the case of Serratia spp., has been obviously varied by the
      influence of factor and operation.

PMID- 8558759
TI  - Analysis of left atrioventricular plane movement during diastole in ischemic
      heart disease.
AB  - The aim of the present study was to investigate the properties of diastolic left
      atrioventricular plane displacement (AVPD) in coronary artery disease (CAD)
      patients. In 125 patients (mean age 58.7 +/- 13.7) with CAD and in 51 age-matched
      healthy subjects, a complete transthoracic echocardiographic study was performed.
      The AVPD was recorded by M-mode echocardiography, from apical four and two
      chamber views at four sites corresponding to the septal, lateral, anterior and
      inferior walls of the left ventricle. Mean AVPD in early diastole (E-AVPD), mean
      AVPD from atrial systole (A-AVPD) and the ratio A-AVPD/E-AVPD were determined. In
      normal subjects, such as in 35 patients without left ventricular segmental wall
      motion abnormalities (SWMA), stepwise multiple regression analysis showed none of
      these factors to be significantly related to E-AVPD or A-AVPD. Aging was
      correlated negatively to the E-AVPD/A-AVPD ratio (p < 0.05). In 90 patients with
      left ventricular SWMA, stepwise multiple regression analysis showed that indices
      of left ventricular systolic function correlated positively to E-AVPD (p < 0.001)
      and A-AVPD (p < 0.001). The E-AVPD/A-AVPD ratio was correlated to left
      ventricular ejection fraction and heart rate (p < 0.005). Mean E-AVPD was
      significantly lower in CAD patients than in normal subjects (p 0.001), while A
      AVPD was higher in patients without left ventricular SWMA in comparison to normal
      subjects (p = 0.02). Also, mean A-AVPD/E-AVPD was higher in CAD patients than in
      the control group (p < 0.001). Mean E-AVPD/A-AVPD was correlated to the E/A ratio
      of transmitral flow in CAD patients with (r = 0.669) and without (r = 0.771)
      SWMA. The E-AVPD and A-AVPD in CAD patients with SWMA is reduced according to the
      deterioration of left ventricular systolic function. The atrial contribution to
      the longitudinal distension of the left ventricle is increased in CAD patients.
      In CAD patients, especially those without left ventricular SWMA, the E-AVPD/A
      AVPD ratio has a good correlation to left ventricular filling behavior.

PMID- 8558760
TI  - Association of ACE gene polymorphisms with coronary artery disease in a northern
      area of Japan.
AB  - The insertion/deletion DNA polymorphism of the gene coding human angiotensin
      converting enzyme (ACE) was examined in 109 patients with coronary artery disease
      (CAD) and 93 non-coronary subjects (NCS) living in a northern part of Japan. The
      presence of risk factors including age, hypertension, hypercholesterolemia,
      tobacco use, diabetes mellitus and hyperuricemia were also examined. An insertion
      (I) / deletion (D) polymorphism of the ACE gene was determined by the polymerase
      chain reaction with oligonucleotide primers encompassing the polymorphic region
      in intron 16. The template DNA was isolated from peripheral blood leukocytes of
      patients. The frequency of the D-allele in NCS was 0.27, significantly lower than
      that reported in Caucasians or in Japanese living in the Osaka area. The
      frequency of the D-allele in patients with myocardial infarction (MI) and angina
      pectoris was 0.39 and was higher than that in NCS. The frequencies of genotypes
      DD, ID, and II were 17.8, 43.3 and 38.9%, respectively, in CAD except in young
      patients (below 40 years of age) with MI and AP groups, and 6.5, 40.9 and 52.7%,
      respectively in NCS (p < 0.05 between CAD and NCS). Young MI showed similar
      frequencies in ACE gene polymorphisms to those in NCS, a pattern which differed
      from that seen in subjects with CAD (p < 0.05). The numbers of risk factors did
      not alter the frequency of ACE gene genotype among patients with CAD, however, in
      normotensives, the odds ratio of DD-genotype was significantly increased to 3.4.
      Accordingly, ACE gene polymorphism may be associated with morbidity from CAD in
      Japanese living in northern Japan as has been noted in Caucasians, despite the
      lower frequencies of the D-allele in the Japanese population.

PMID- 8558761
TI  - Comparison of long-term efficacy of medical treatment versus percutaneous
      transluminal coronary angioplasty (PTCA) in single-vessel disease.
AB  - The long-term outcome of PTCA and medical therapy were compared in patients with
      SVD. All patients were confirmed to have > or - 75% stenosis of a major coronary
      artery by coronary arteriogram. The 5-year survival rates were 96.0% for medical
      therapy and 98.9% for successful angioplasty. Both therapies achieved an equally
      good long-term outcome for SVD. The incidence of nonfatal cardiac events during
      follow-up was higher in patients treated by PTCA than in those on medical
      therapy, but there was no difference between the two groups in the incidence of
      nonfatal MI at 5 years (2.5% vs 1.8%). The most common cardiac event in patients
      undergoing successful PTCA was repeat intervention associated with restenosis. In
      view of the long-term efficacy of PTCA, the high restenosis rate remains an
      important problem and it is necessary to elucidate the causes of restenosis and
      develop countermeasures as soon as possible.

PMID- 8558762
TI  - QT dispersion in acute myocardial infarction with special reference to left
      ventriculographic findings.
AB  - QT and QT dispersion, which is the time difference between QT maximum and QT
      minimum, were evaluated in 22 patients with anterior myocardial infarction
      approximately one month after onset. The purpose of this study was to observe how
      LV wall motion abnormally is related to these variables. Twenty age-matched
      patients without overt heart disease were also studied as a control group. QT and
      QT max in patients with acute myocardial infarction (AMI) were markedly prolonged
      compared to those in normal controls (472.8 +/- 48.0, 483.2 +/- 32.1 vs 390.2 +/-
      18.8, and 418.0 +/- 21.0 msec, respectively). QT dispersion and QTc dispersion in
      patients with AMI were significantly more prolonged than in normal controls
      (111.2 +/- 33.9, (113.4 +/- 32.9 vs 54.3 +/- 15.0, and 60.3 +/- 17.2 msec,
      respectively). QT dispersion has a positive correlation with QT max in AMI
      patients. Ejection fraction (EF) of the left ventricle was relatively well
      maintained in cases where only one segment of the left anterior ventricular wall
      was impaired in its motion. It decreased, however, in accordance with the extent
      of wall motion abnormality QT max and QTc max were prolonged as the number of LV
      wall segments with impairment increased. This, however, was not statistically
      significant. QT dispersion and QTc dispersion had no relation to the extent of LV
      wall motion abnormality nor to EF of the left ventricle In conclusion, no
      definite relationships between QT dispersion (QTc dispersion) and EF of the left
      ventricle, or between these variables and the extent of left ventricular wall
      motion abnormality were found in patients with anterior myocardial infarction in
      our study. Although both QT max and QT dispersion were prolonged in patients with
      myocardial infarction, this suggests that electrical heterogeneity or regional
      variation in electrical ventricular recovery did not always parallel the severity
      of mechanical abnormality of the left ventricle.

PMID- 8558763
TI  - I-123 metaiodobenzylguanidine cardiac scintigraphy in patients with an implanted
      permanent pacemaker.
AB  - T1 scintigraphic abnormalities have been reported in patients with an implanted
      permanent pacemaker, but little is known about the MIBG scintigraphic findings in
      such patients. This study was performed to assess the MIBG scintigraphic findings
      in patients with an implanted permanent pacemaker, and to test the hypothesis
      that imaging characteristics of MIBG scintigraphy differ according to its mode.
      Twelve patients (4 men and 8 women, mean age: 72.4 +/- 9.5 years), who had
      undergone the implantation of a permanent pacemaker for bradyarrhythmias,
      underwent MIBG scintigraphy. The patients were divided into VVI pacemaker and DDD
      pacemaker groups. The tomograms were divided into nine segments and the MIBG
      defect in each segment scored on a scale ranging from 0 (normal uptake) to 3 (no
      uptake). Total MIBG defect scores were generated by summing the scores for the
      nine segments in each patient. MIBG scintigraphic abnormalities were found in ten
      of the twelve patients. The six patients with the VVI pacemaker manifested MIBG
      scintigraphic abnormalities. These MIBG scintigraphic abnormalities were observed
      in all segments, particularly in the posterior segments. The mean total defect
      score of the VVI group was higher than that of the DDD group (14.8 +/- 9.8 vs 3.0
      +/- 3.5, respectively p < 0.05). Therefore, we conclude that despite several
      limitations of the study, MIBG scintigraphic abnormalities occur in patients with
      implanted permanent pacemakers, and that such abnormalities are more prominent
      with the VVI than DDD pacemaker.

PMID- 8558764
TI  - Intraoperative evaluation of myocardial viability by nitroglycerin-induced
      improvement in regional left ventricular function assessed by transesophageal
      echocardiography.
AB  - The aim of this study was to assess whether intraoperative transesophageal
      echocardiography with nitroglycerin infusion could identify viable myocardium.
      Twenty-eight patients with coronary artery disease with regional dysfunction
      underwent transesophageal echocardiography during bypass surgery. A transgastric
      left ventricular cross-sectional image at the midpapillary level was obtained and
      divided into four segments for wall motion analysis. Forty-four segments were
      graded as asynergic. Nitroglycerin was then given intravenously with an initial
      infusion rate of 1 microgram/kg/min, followed by an increase in dose up to 3
      micrograms/kg/mini. Functional improvement with nitroglycerin was observed in 33
      or 44 asynergic segments, while 11 remained unchanged. Follow-up transthoracic
      echocardiography was performed at 15.9 +/- 5.5 days after surgery. A segment was
      defined as viable when wall motion was better than or equal to severe hypokinesis
      at baseline or follow-up. Forty-three of 44 asynergic segments at baseline were
      defined as viable; these were the same segments demonstrating wall thickening
      with nitroglycerin. In particular, four of 5 akinetic segments at baseline
      demonstrated viability at follow-up, which had been predicted with nitroglycerin.
      Transesophageal echocardiography with nitroglycerin correctly identified
      viability (p < 0.05). No adverse hemodynamic effect was observed. Intraoperative
      transesophageal echocardiography with nitroglycerin appears to be a safe,
      noninvasive, feasible, and widely available method to identify myocardial
      viability under the condition supported by cardiopulmonary bypass.

PMID- 8558765
TI  - Simulation of chronic mitral regurgitation.
AB  - In mitral regurgitation the left ventricle enlarges in order to increase its
      stroke volume because of the regurgitation through the mitral valve. The amount
      of this volume increase, and of the consequent increase in left ventricular mass,
      its dependent upon the amount of the regurgitant volume, but many other factors
      come into play, such as left ventricular pumping capability (contractility), the
      level of peripheral pressure, resistance and compliance of the arterial tree. The
      aim of this study is to predict the final left ventricular volumes and mass given
      the amount of mitral regurgitation. The predicted results are compared with
      actual data in real patients. In most cases prediction is fairly good; some
      discrepancies can be interpreted as an index of advanced decompensation.

PMID- 8558766
TI  - Evaluation of left ventricular diastolic hemodynamics from the left ventricular
      inflow and pulmonary venous flow velocities in hypertrophic cardiomyopathy.
AB  - We evaluated the characteristics of left ventricular diastolic hemodynamics in
      hypertrophic cardiomyopathy (HCM) by measuring left ventricular inflow (LVIF) and
      pulmonary venous flow (PVF) velocities in 62 patients with asymmetric septal
      hypertrophy and 34 normal controls. The patients were divided into four groups
      according to the LVIF pattern and left ventricular end-diastolic pressure
      (LVEDP): 1) the pseudonormalization group; 13 patients with the ratio of peak
      atrial systolic (A) to early diastolic (E) LVIF velocity (A/E) < or = 1 and LVEDP
      > or = 15 mm Hg, 2) the normal pattern group; 10 patients with the A/E < or = 1
      and LVEDP < 15 mm Hg, 3) the relaxation failure group; 25 patients with the A/E >
      1, and 4) the mid-diastolic wave group; 14 patients with a mid-diastolic wave.
      The peak early diastolic LVIF velocities in the pseudonormalization, relaxation
      failure and mid-diastolic wave groups were significantly smaller than in the
      control group. The deceleration time from the peak of the E wave and the
      isovolumic relaxation time were significantly prolonged in the relaxation failure
      and mid-diastolic wave groups. The peak diastolic PVF velocity in the relaxation
      failure and mid-diastolic wave groups was significantly decreased, and was
      significantly increased in the pseudonormalization group. The peak atrial
      systolic PVF velocity was significantly increased in all patients with HCM,
      particularly in the pseudonormalization group. LVEDP was the highest in the
      pseudonormalization group, followed by the mid-diastolic wave, relaxation failure
      and normal pattern groups, in that order. In conclusion, combined analysis of the
      LVIF and PVF provides useful information regarding various abnormalities of left
      ventricular diastolic hemodynamics in patients with HCM.

PMID- 8558767
TI  - The effects of nisoldipine on carotid artery stiffness and left ventricular
      functions.
AB  - Doppler echocardiographic determination, left ventricular (LV) fractional
      shortening (FS), cardiac output (CO), diastolic function parameter (E/A ratio)
      and carotid artery pulse wave velocity and stiffness were evaluated in 36
      patients with essential hypertension before and after nisoldipine treatment.
      Blood pressure decreased significantly, and carotid artery width and fractional
      shortening increased significantly following nisoldipine administration (p <
      0.0001). Carotid artery pulse wave peak velocity did not change following the
      treatment period (p > 0.05). In conclusion, short term nisoldipine administration
      improved blood pressure and LV systolic function, whereas LV diastolic function
      and carotid artery stiffness did not change. Nisoldipine did not alter serum
      biochemical parameters, including cholesterol, triglyceride, HDL-cholesterol, and
      LDL-cholesterol (p > 0.05). Only one patient manifested symptoms of hypotension
      as an adverse effect of the drug.

PMID- 8558768
TI  - Aortic dissection in Taiwan.
AB  - We retrospectively reviewed all patients with a final diagnosis of spontaneous
      thoracic aortic dissection treated at Linkou Chang Gung Memorial Hospital between
      January 1989 and December 1994. There were a total of 109 patients with a mean
      age of 55 +/- 11 years ranging from 19 to 88 years. The male-to-female ratio was
      2 to 1 (73 to 36). There was a predilection to present during the colder months,
      with 69% seen between September 1 and February 28 and only 31% during the warmer
      half of the year. In most patients, hypertension (85%) was the major predisposing
      factor with another 7% having Marfan syndrome. The remaining 8% had no obvious
      underlying disease except for one patient who had an atrial septum defect.
      Presenting chief complaints in order of frequency included: anterior chest pain
      58.7% (64/109), back pain 19.2% (21/109), abdominal pain 10.1% (11/109),
      consciousness change 3.7% (4/109), neck pain 2.7% (3/109), paraparesis 2.7%
      (3/109), dyspnea 1.8% (2/109), and hemoptysis 0.9% (1/109). The diagnostic
      breakdown revealed 46% to be type A (50/109) and 54% type B (59/109). A total of
      26 (24%) patients died in hospital (16% were type A and 8% were type B). (Type A
      included all proximal dissections and those distal dissections that extend
      retrograde to involve the arch and ascending aorta; Type B refers to the other
      distal dissections without proximal extension; proposed by Daily et al.) Thoracic
      aortic dissection remains an important concern in patients with a history of
      hypertension. Patients seem particularly susceptible during cold weather months.
      The average age of our patients was only 55 years and 24% of them died during
      hospitalization. Earlier identification and more aggressive antihypertensive
      treatment is required.

PMID- 8558769
TI  - Intracellular sodium concentration in diabetic rat ventricular myocytes.
AB  - We measured intracellular NA+ concentration ([Na+]i) of diabetic rat ventricular
      myocytes using sodium-binding benzofuran isophthalate (SBFI). We used diabetic
      rats at 8 weeks after the injection of streptozotocin (45 mg/kg i.v.). The level
      of [Na+]i during the control perfusion was significantly lower in diabetic
      myocytes than that in normal myocytes (9.2 +/- 0.4 mM v.s. 12.0 +/- 0.3 mM, p <
      0.01). After the 40 min perfusion of 1 microM hexamethylene amiloride (HMA),
      [Na+]i decreased significantly in both groups. However, there was no difference
      in [Na+]i between the two groups after the perfusion of HMA. It was suggested
      that the lower [Na+]i in diabetic myocytes could be due to the decreased activity
      of Na+/H+ exchange system.

PMID- 8558770
TI  - Local delivery of heparin inhibits neointimal hyperplasia in injured rabbit
      artery.
AB  - The efficacy of local delivery of an antithrombotic drug on neointimal
      hyperplasia was investigated in 17 rabbits. One rabbit iliac artery was injured
      by a balloon catheter as a control injured artery. The other iliac artery was
      also injured and treated by local delivery of 25 U/kg of heparin. One hour after
      the balloon injury, angioscopy demonstrated an occlusive or mural thrombus in all
      the controls, but few in the locally-treated arteries. Four weeks after balloon
      injury, the percent stenosis was 34 +/- 31% in the heparin treated group (n = 7,
      p < 0.005) vs control side 73 +/- 17%). Accumulation of FITC-labeled heparin at
      the injured site was confirmed by microscopy. The activated partial
      thromboplastin time and fibrinogen level did not change significantly. PDGF-B
      chain was prominent at the neointimal layer in all the controls, whereas it was
      less in the locally treated arteries. Thus local delivery of heparin can inhibit
      neointimal hyperplasia after balloon injury by reducing thrombus-related growth
      stimulation.

PMID- 8558771
TI  - Vasospastic angina in two sisters.
AB  - Vasospastic angina was observed in two sisters. The 52-year-old younger sister
      presented with rest angina at midnight and in the early morning. The coronary
      arteriogram showed no significant organic stenosis. Vasospasm to the left
      anterior descending and right coronary arteries was induced by the intracoronary
      administration of acetylcholine. The 57-year-old elder sister complained of rest
      and effort angina. Her coronary arteriogram was also normal. Vasospasm to the
      left circumflex and right coronary arteries was provoked by acetylcholine. In
      both cases, human leukocyte antigen DQw3 was negative. In the present cases,
      genetic factors may partly contribute to the mechanism of vasospastic angina.

PMID- 8558772
TI  - A surgically treated case of both Wolff-Parkinson-White syndrome and atrial
      septal defect complicating single coronary artery and partial pericardial defect.
AB  - A surgically treated case of both Wolff-Parkinson White syndrome and atrial
      septal defect complicating a single coronary artery and partial pericardial
      defect is reported. These complications are very rare. In addition, the accessory
      pathway of this case had unique decremental conduction characteristics.

PMID- 8558773
TI  - Systemic amyloidosis following ankylosing spondylitis associated with congestive
      heart failure. A case report.
AB  - We report the case of a 38-year-old man who developed fatal, systemic amyloidosis
      following ankylosing spondylitis. He was admitted for symptoms of congestive
      heart failure. Based on parotid gland biopsy and echocardiography, he was
      diagnosed as having systemic amyloidosis following active ankylosing spondylitis.
      However, the clinical course was rapidly progressive and eventually the patient
      died of acute necrotizing pancreatitis. The association has been reported thus
      far in a limited number of cases worldwide. The literature has featured localized
      lesions and a benign clinical course of the amyloidosis. This case, the first
      report from Japan, indicates that the amyloidosis associated with ankylosing
      spondylitis might exhibit a rapidly progressive clinical course, thereby
      suggesting that in such a case, meticulous treatment is required.

PMID- 8558774
TI  - [Progress in pancreatic endocrine tumor surgery: with special reference to the
      Zollinger-Ellison syndrome].

PMID- 8558775
TI  - [Immunological effect of immunoglobulin on experimental colitis induced by
      dextran sulfate].
AB  - To clarify the mechanism of action of immunoglobulin (IgG) in intravenous
      immunoglobulin therapy for ulcerative colitis (UC) patients, we studied the
      effect of IgG on the dynamics of immunocompetent cells in the colonic mucosa of
      experimental colitis induced by dextran sulfate sodium (DSS) in rats. The
      administration of the same species' IgG suppressed the mucosal infiltration of
      immunocompetent cells (activated T cells, macrophages and neutrophils), although
      the different species' IgG didn't. We have already shown that the same species'
      IgG, suppressed the production of inflammatory cytokines (TNF alpha, IL-1 alpha
      and IL-8) in the colonic mucosa of experimental colitis induced by DSS. In the
      present report, we demonstrated the different species' IgG, as well as same
      species' IgG, suppressed the production of inflammatory cytokines (TNF alpha and
      IL-1 alpha) from lamina propria mononuclear cells of rat large intestine in
      vitro. Therefore, it was considered that the suppression of cytokine production
      was a consequence of the decreased immunocompetent cells in colitis mucosa.
      Furthermore, we demonstrated that the DSS-treated antigen presenting cells (APCs)
      activated antigen-specific T cells as a possible mechanism underlying the colitis
      induced by DSS and the same species' IgG inhibited this activation of T cells.

PMID- 8558776
TI  - [Overexpressed p53 protein and cell-proliferative activity disappear or
      remarkably decrease in neoplastic CGA-positive endocrine and Paneth cells in
      cancer or dysplasia of ulcerative colitis].
AB  - We examined over-expression of p53 protein and proliferative activity of
      neoplastic endocrine and Paneth cells in cancer or dysplasia of ulcerative
      colitis (UC). The labeling index of p53 or Ki-67 of endocrine cells was counted
      with double immunostaining of p53 or Ki-67 and chromogranin A (CGA). 540 CGA
      positive cells and 65 Paneth cells were all negative for p53. 5.1% of CGA
      positive cells and none of 56 Paneth cells were positive for Ki-67 reaction.
      These observation suggest that even in cancer or dysplasia of UC cell
      differentiation to neoplastic endocrine and Paneth cells decrease proliferative
      activity, and that these types of cell-differentiation suppress over-expression
      of p53 protein.

PMID- 8558777
TI  - [The pharmacokinetics of the glycyrrhizin and glycyrrhetic acid after intravenous
      administration of glycyrrhizin for the patients with chronic liver disease caused
      by type C hepatitis virus].
AB  - Glycyrrhizin had been used widely for the patients with chronic liver disease. We
      examined the pharmacokinetics of the glycyrrhizin and glycyrrhetic acid in the
      blood stream after intra-venous administration of glycyrrhizin. The stream
      concentration of glycyrrhizin in the patients of liver cirrhosis tend to be kept
      higher than that of chronic hepatitis but there were no significant difference
      between them except for after a half hour from the administration. There was
      negative correlation between ICG R15 and the speed of excretion of glycyrrhizin
      from the serum. On the other hand, the concentration of the glycyrrhetic acid was
      kept higher in the patients with liver cirrhosis than that of chronic hepatitis,
      but there were no significant difference between them except for after a half
      hour from the administration. These findings suggested that the accumulation of
      glycyrrhizin and glycyrrhetic acid in the patients of liver cirrhosis can be seen
      by long term administration.

PMID- 8558778
TI  - [A case report of gastric leiomyoblastoma showing exogastric pedunculated
      development].

PMID- 8558779
TI  - [A case report: giant gastric leiomyosarcoma, showing pedunculated extragastric
      development].

PMID- 8558780
TI  - [A case of extraluminally growing giant gastric leiomyoblastoma].

PMID- 8558781
TI  - [A case of gastric MALT lymphoma diagnosed by jumbo biopsy using endoscopic
      mucosal resection].

PMID- 8558782
TI  - [Seven cases of ulcerative colitis associated with pyoderma gangrenosum].

PMID- 8558783
TI  - [Ulcerative colitis in female monozygotic twins].

PMID- 8558784
TI  - [A case of ileocecal actinomycosis with marked swelling of ileocecal valve].

PMID- 8558786
TI  - [A case of mucinous cystadenocarcinoma of the pancreas with intraductal growth to
      the main pancreatic duct].

PMID- 8558785
TI  - [A case of liver abscess caused by lapaloscopic liver biopsy after endoscopic
      sphincteropapillotomy (EST) during to the interferon therapy].

PMID- 8558787
TI  - [Helicobacter pylori in intractable gastric ulcer and cagA gene].

PMID- 8558788
TI  - [Quantification of renal function with 99mTc-MAG3--quantification of tubular
      extraction rate using Bubeck's method].
AB  - 99mTc-mercaptoacetyltriglycine (MAG3) is a new agent for dynamic renal
      scintigraphy. It provides not only superior quality of imaging to conventional
      agents such as 131I-orthoiodohippurate or 99mTc-demethylenetriaminepantaacetic
      acid but also quantification of renal function as do the latter agents. The aim
      of the present study was to evaluate the value of the tubular extraction rate
      (TER) using 99mTc-MAG3 calculated by Bubeck's method, a simple technique for
      quantifying renal function. In 31 patients with renal disorders, we compared the
      TER thus obtained with laboratory data, plasma paraaminohippurate clearance,
      effective renal plasma flow calculated by Tauxe's method, and plasma 99mTc-MAG3
      clearance calculated according to the two-compartment model. TER was easily
      applicable in clinical settings, and showed close parallels with the other
      indexes of renal function. We believe, therefore, that it can serve as a useful
      parameter of renal function.

PMID- 8558789
TI  - [Prognostic significance of 123I-metaiodobenzylguanidine scintigraphy in dilated
      cardiomyopathy].
AB  - The prognostic factor was identified by performing 123I-Metaiodobenzylguanidine
      (MIBG) myocardial scintigraphy on 17 patients with dilated cardiomyopathy (DCM).
      During 5 years period, 9 patients had cardiac events, four of whom died, six were
      admitted due to heart failure and five had ventricular tachycardiac events. At
      the starting point, we collected rest early and 3-hr-delayed MIBG SPECT along
      with rest 201T1 (T1) SPECT. In the SPECT, regional tracer uptake was scored using
      4-grades defect score (0 = normal to 3 = uptake-defect), and summed up to total
      defect score (TDS). At the same time, we estimated left ventricular end-diastolic
      dimension/body surface area (LVDd/BSA), end-systolic dimension/body surface area
      (LVDs/BSA) and left ventricular ejection fraction (LVEF) by echo-cardiography,
      pulmonary arterial wedge pressure (PAWP) and New York Heart Association (NYHA)
      symptom class. We compared the clinical and hemodynamic parameters between the
      patients with cardiac events (group A) and the other patients (group B). TDS of
      delayed MIBG SPECT (p < 0.001), TDS of early MIBG SPECT (p < 0.05), TDS of T1
      SPECT (p < 0.01), LVDd/BSA (p < 0.01), LVDs/BSA (p < 0.001) and NYHA class (p <
      0.05) of group A were significantly larger than those of group B. But, LVEF of
      group A was significantly less than that of group B (p < 0.01). On multivariate
      analysis, the following parameters were independent predictors of cardiac events:
      TDS of delayed MIBG SPECT (p < 0.001), PAWP (p = 0.0124) and LVDd/BSA (p =
      0.0026). These data suggest that delayed MIBG scintigraphy is thought to be
      important to predict cardiac events in patients with DCM.

PMID- 8558790
TI  - [A time-saving approach for quantifying regional cerebral blood flow and
      application to split-dose method with 123I-IMP SPECT using a single-head rotating
      gamma-camera].
AB  - We have proposed a modified early method, which can shorten the total time
      required for the quantitative regional cerebral blood flow (rCBF) measurement
      with N-isopropyl-p(-)[123I]iodoamphetamine (123I-IMP) using single-head rotating
      gamma-camera and the continuous arterial sampling method. Between 7 to 25 minutes
      after the intravenous injection of 123I-IMP, brain activity increases linearly,
      the SPECT data acquisition is being performed, and during which detector is
      rotating continuously. Then the rCBF values based on the microsphere model were
      calculated using the planar images obtained before and after the above
      acquisition and 5 min after the injection, and input counts obtained by the
      continuous arterial sampling. A good correlation (r = 0.951) was observed between
      the rCBF values obtained by this method and the traditional method, in which the
      SPECT data acquisition started about 30 min after injection. Applying this method
      to the quantitative rCBF measurements at rest and during stress with Diamox by
      the split dose method of 123I-IMP, we could evaluate the rCBF at rest and
      cerebral perfusion reserve in the same day. We conclude that this method can
      shorten the total time required for the standard normal microsphere method and
      can be applied to the split dose method, and this method provide the rCBF values
      not so much affected by washout of the tracer from the brain.

PMID- 8558791
TI  - [Assessment of left ventricular contraction kinetics by ECG-gated myocardial
      SPECT with 99mTc-MIBI: a new attempt with multi-plane long axial tomography].
AB  - To investigate left ventricular (LV) contraction kinetics, we performed ECG gated
      myocardial tomography (gated-SPECT) with 99mTc-MIBI (99mTc methoxy-2-isobutyl
      isonitrile) at rest. Data were obtained from 32 views and R-R interval was
      divided into 16. To clarify whether myocardial count change during systole (%CC)
      reflected LV wall thickening (%WT), we compared septal and posterior %CC in short
      axis image with %WT which were obtained by echocardiography. And %CC correlated
      well with %WT (r = 0.86, p < 0.01). In order to assess myocardial contraction
      kinetics in various parts of LV, multi-plane long axial tomograms were
      constructed in 10 normal subjects and 9 patients with myocardial infarction (MI).
      By multi-plane long axial tomography, LV was divided into 17 segments. In each
      segment %CC was calculated from time activity curves of myocardial count of 99mTc
      MIBI. And the disparity of the appearance of peak count in each segment was also
      observed. In normal subjects %CC was greatest at apex and they decreased from
      apex to cardiac base. Besides %CC at lateral segments was greater than that in
      septal segments. Normal range of %CC was determined segment by segment. In normal
      subjects the intervals from ECG R-wave to peak count were not different in each
      segment. But in patients with MI they distributed in wide range and prolonged
      intervals were observed in segments with rest perfusion defect (infarcted
      segment). In patients with MI decreased %CC was observed in 91% of infarcted
      segments, in 83% of the segments with exercise induced ischemia and in 89% of the
      segments with 123I-BMIPP defects. These results indicated decreased %CC
      represented viable but compromised myocardium as well as necrotic myocardium. In
      gated-SPECT we obtained useful informations in addition to myocardial perfusion.
      But it took more than 30 minutes to perform. More experience will be necessary to
      ascertain the value of this technique.

PMID- 8558792
TI  - [99mTc-ECD dynamic SPECT in "luxury perfusion" of subacute stroke].
AB  - To evaluate the cerebral pharmacokinetics of 99mTc-ethyl cysteinate dimer (99mTc
      ECD) at blood flow levels beyond the normal range, we investigated "luxury
      perfusion" in subacute stroke, ictal hyperperfusion in epilepsy and post
      decompressive hyperemia in head trauma. All 7 patients showed a hyperactive area
      on SPECT studies using 99mTc-HM-PAO. 99mTc-ECD static image demonstrated a
      hyperactive area in both epilepsy and head trauma, and a hypoactive area in
      "luxury perfusion." On the dynamic SPECT of 99mTc-ECD in both epilepsy and head
      trauma, brain distribution of the tracer was determined within 2 min.
      postinjection and remained stable for up to 1 hour; however, "luxury perfusion"
      area showed a change from initial hyperactivity to late hypoactivity with the
      passage of time. The time activity curve in "luxury perfusion" area demonstrated
      a steep decrease of counts/pixel for up to 4-5 minutes postinjection, and a
      moderate decrease in the following phase. The early wash-out mechanism of 99mTc
      ECD from "luxury perfusion" area can be described by a biexponential function
      including an initial steep decrease representing the rapid loss of the lipophilic
      complexes which were not metabolized in injured brain tissue.

PMID- 8558793
TI  - [Clear skeletal visualization on whole body 201Tl-chloride scintigraphy: a case
      of prostatic cancer with diffuse bone metastases].
AB  - A 70-yr-old man who was diagnosed as early gastric cancer showed leukocytopenia
      after total gastrectomy. Osteosclerotic findings on radiography were not
      remarkable. 99mTc-HMDP bone scintigraphy showed diffusely increased uptake in the
      axial skeleton, but visualization of the kidney and urinary bladder was apparent.
      However, whole body 201Tl-chloride scintigraphy showed diffuse abnormal
      visualization of axial skeleton. Physical and ultrasonographic examination
      indicated no abnormality in prostate. Afterward, further investigation, including
      bone marrow biopsy and immunohistochemical study, confirmed the diagnosis of bone
      metastasis from prostatic cancer. Microscopically, metastatic tumor cells were
      located in the intertrabecular space. Furthermore, no osteoclastic bone
      resorption or new trabecular bone formation was seen in this biopsy specimen.
      These findings suggest that whole body 201Tl-chloride scintigraphy can be a
      useful non-invasive diagnostic tool to investigate patients with suspicious
      malignancy in the bone marrow.

PMID- 8558794
TI  - [Quantitative changes in cerebral blood flow of Shy-Drager syndrome induced by
      upright position: assessment by 99mTc-HMPAO].
AB  - We assessed orthostatic changes of cerebral blood flow (CBF) in 4 patients with
      Shy-Drager syndrome. Brain perfusion index (BPI) was measured by 99mTc
      hexamethylpropylene amine oxime (99mTc-HMPAO). Cerebral angiography using aortic
      time-activity curve as an input function BPI values in supine and upright
      positions in Shy-Drager syndrome were compared with those in 2 cerebrovascular
      disease patients without orthostatic hypotension. BPI values in the upright
      position were significantly decreased in patients with Shy-Drager syndrome as
      compared with these in the supine position. No significant decrease in BPI was
      noted in the patients without orthostatic hypotension. These results suggest that
      the BPI measurement by 99mTc-HMPAO cerebral angiography is useful for the
      noninvasive evaluation of the orthostatic changes of the CBF.

PMID- 8558795
TI  - [Comparative examinations of serum pepsinogen I, II and gastric area using
      computed radiography in the atrophic gastritis].
AB  - The relationship between serum PG I, PG II levels and extent of atrophic
      gastritis was examined. On 64 patients (male: 32, female: 32, 51.9 years old on
      average) with established diagnosis of either atrophic gastritis or normal. In
      the X-ray gastric examination, Fuji Computed Radiography (FCR) was used to obtain
      clear-cut images of the gastric area. Concerning the serum PG I level, patients
      in the group with atrophic gastritis showed lower levels than those of the people
      in the group with no atrophic change, but the variation was wide, and no definite
      tendency was seen in the relationship between the atrophic change and the serum
      PG I levels. Concerning the serum PG II level, as the atrophic change progresses,
      the serum PG II level tended to increase gradually. A significant reduction in
      the PG I/II ratio was seen in the group with atrophic changes (p < 0.01) in
      comparison with the group with no atrophic changes, and the PG I/II value tended
      to decrease. In conclusion, as a relationship between the atrophic change and the
      serum PG levels had a wide variation, we considered to be difficult by to measure
      the serum PG level to understand the presence and extent of the atrophic
      gastritis.

PMID- 8558796
TI  - [Imaging of infectious and inflammatory foci using 111In-DTPA-IgG].
AB  - We performed radionuclide scanning after intravenous administration of 80 MBq of
      111In-labeled non-specific polyclonal human immunoglobulin G (111In-DTPA-IgG).
      Serial scintigrams were acquired at 6, 24, 48, and 72 hr after injection in 10
      patients suspected of having inflammation and/or infection. In 5 patients, the
      results of scintigraphy were verified with intraoperative cultures or biopsy. The
      values were as follow: sensitivity: 100% (4/4); specificity 50% (3/6); accuracy:
      70% (7/10); positive predictive value: 57.1% (4/7); and negative predictive
      value: 100% (3/3). The results indicate that 111In-DTPA-IgG scintigraphy is
      certainly a promising method for the detection of inflammation and/or infection.

PMID- 8558798
TI  - [Pulmonary nuclear medicine].
AB  - Pulmonary nuclear medicine dates back to Knipping and West in the late 1950's but
      practically starts with the successful production of 131I-MAA by GV Taplin in
      1963. Not only is the diagnosis of pulmonary embolism greatly facilitated by
      using 131I-MAA but also studies of regional lung function have made rapid
      progress. Radioactive gas and aerosol inhalation have been used to study
      ventilation distribution in the lungs. Using nuclear medicine technology regional
      hypoxic vasoconstriction was found to play a great role in regulating regional
      perfusion distribution in the lungs. Ventilation and perfusion mismatch and match
      indicate organic lung diseases and pulmonary vascular diseases, respectively.
      Aerosol deposition patterns in the lungs are helpful in the differential
      diagnosis of chronic obstructive lung diseases (COPD). Technigas is an ultrafine
      aerosol which is probably more useful for ventilation studies than conventional
      aerosols produced by either a jet or an ultrasonic nebulizer. Besides respiratory
      lung function pulmonary nuclear medicine techniques have made it possible to
      study nonrespiratory lung function. One is mucociliary clearance mechanisms. They
      can be studied by using a nonabsorbable aerosol like 99mTc-albumin. Dynamic
      mucociliary clearance function can be visualized in vivo by radioaerosol
      inhalation lung cine-scintigraphy. Four abnormal mucociliary transport patterns
      were discernible in COPD. An objective evaluation of a drug effect on mucociliary
      transport is feasible. Detailed quantitative analysis of mucociliary clearance is
      also possible by computer techniques. Pulmonary epithelial permeability is
      studied following inhalation of 99mTc-DTPA aerosol. Inhaled 99mTc-DTPA disappears
      from the lungs more rapidly in smokers and patients with interstitial lung
      diseases. Nuclear medicine has great potential to elucidate other functions of
      the lung which are still not defined yet by the present knowledge of lung
      function.

PMID- 8558797
TI  - [Phase 3 multicenter clinical study of 111In-DTPA-D-octreotide (MP-1727) in
      patients with gastrointestinal hormone producing tumors].
AB  - A phase 3 multicenter clinical study was performed to investigate the efficacy,
      safety and usefulness of MP-1727, a novel tumor imaging agent which binds to
      somatostatin receptors, in 23 patients with gastrointestinal hormone producing
      tumor. The efficacy was graded effective or very effective in 16 cases (76.2%)
      out of 21 cases who could be evaluated. Positive predictive accuracy was 77.8%
      (7/9) for carcinoids, 100% (5/5) for gastrinomas and 40.0% (2/5) for insulinomas.
      In three cases, tumor lesions which had been unknown were detected by MP-1727
      scintigraphy. The consistent ratio between scintigraphically positive sites and
      preinjection localizations was 82.0% (41/50 sites) in total. Although adverse
      drug reactions were observed in two cases, the safety was graded 'not problematic
      at all' in all of 23 cases. These results show that MP-1727 is a very useful
      radiopharmaceutical for detection and localization of gastrointestinal hormone
      producing tumors.

PMID- 8558799
TI  - [Chest wall reconstruction using polyester mesh].
AB  - From January 1987 through December 1994, we performed chest wall reconstruction
      using the polyester mesh in 15 patients with lung cancer, 11 with empyema after
      open drainage, 8 with chest wall tumor and 1 with radiation dermatitis and costal
      chondritis. Twenty five patients were resected 3 or more ribs. Chest wall defects
      were reconstructed with the polyester mesh covered with Gore-Tex soft tissue
      patch. Twenty two cases passed more than a year without signs of infection and
      follow-up averaged 27.6 months. Polyester mesh was removed due to bronchial
      fistula (3 cases), deformities (3 cases) and abscess formation (1 case). In these
      cases, polyester mesh was well incorporated and had no foreign body change. In
      conclusion, the polyester mesh seems to be a dependable prosthetic material for
      chest wall reconstruction.

PMID- 8558800
TI  - [A clinical analysis of the patients with chest wall reconstruction].
AB  - Twenty-three patients underwent chest wall reconstruction in our department. The
      underlying disease was bronchial carcinoma in 14, urachus tumor in 2, breast
      cancer in 1, renal cancer in 1, thymic Hodgkin's lymphoma in 1, tuberculosis in
      1, fibrosarcoma in 1, and pseudoaneurysm of the aortic arch caused by
      reconstructed material in 1. An average of 3.4 ribs were resected in 18 patients
      and sternectomies were performed in 5. Chest wall reconstruction was performed
      with Marlex mesh in 14, Marlex mesh with methyl methacrylate in 5, Marlex mesh
      with steel wire in 1, Marlex mesh with omentopexy in 1, Marlex mesh with A-O
      plate in 1, and net formation with catgut in 1. There was no operative death.
      Postoperative wound infection occurred in only 1 patient with Marlex mesh cleaned
      by irrigation and administration of antibiotics. Three patients with Marlex mesh
      and metyl methacrylate required removal of the prosthetic material
      postoperatively because of wound infection in 1, seroma in 1, and dislocation of
      the former reconstructed material in 1. One patient with Marlex mesh and steel
      wire had protrusion of the wire under the skin and the wire was removed. Eleven
      patients of lung cancer died at 2-17 months after surgery. In conclusion, chest
      wall reconstruction with Marlex mesh had excellent results, and chest wall
      resection and reconstruction for malignancy could be good palliation.

PMID- 8558801
TI  - [Resection and reconstruction of full thickness chest wall].
AB  - Nine patients underwent full thickness chest wall resection and reconstruction in
      our department between January 1981 and December 1994. There were chest wall
      recurrence of breast cancer in 5 cases, primary chest wall chondrosarcoma in 2,
      primary chest wall malignant fibrous histiocytoma in 1 and metastatic sternal
      renal cell carcinoma in 1. Seven of 9 cases underwent partial sternal resection.
      Sizes of chest wall defects were from 10 x 7 cm to 15 x 14 cm. In eight cases of
      9, chest wall reconstruction was by double Marlex mesh repairs and various flaps
      (major pectoral muscle in 3, major pectoral myocutaneous flap in 2, latissimus
      dorsi myocutaneous flap in 1 and pedicled omentum in 1). The last case underwent
      repair with rectus abdominis myocutaneous flap without mesh. There was no
      operative death. Postoperative complications occurred in 4 patients: partial skin
      necrosis in 2, skin dehiscence in 1 and respiratory failure in 1. Eight cases are
      alive now from 9 months to 14 years and 8 months after chest wall reconstruction.
      One patient with metastatic renal cell carcinoma died of recurrence 3 years after
      operation. Full thickness chest wall resection and reconstruction is a safe
      operation and may provide a long-term survival.

PMID- 8558802
TI  - [Resection of sternal lesion and its reconstruction].
AB  - Our experience of seven cases with resection and reconstruction of sternum were
      introduced. The lesions were 1 chondrosarcoma, 1 malignant fibrous histiocytoma,
      1 myeloma, 1 fibrous dysplasia, 1 thymic carcinoma and 2 recurrent breast
      carcinomas. Partial resection of sternum was performed in 6 and subtotal
      resection in 1. In reconstruction of sternum we have used frequently Marlex mesh
      for prosthetic material, and pedicled pectoralis major muscle flap and/or rectus
      abdominis musculocutaneous flap for overlying the prosthesis. All patients are
      living and well for except one case.

PMID- 8558803
TI  - [A clinical evaluation of chest wall reconstruction].
AB  - From April 1987 to June 1995, we performed the chest wall reconstruction in 13
      cases of 25 ones who had chest wall resection. The clinical records of these 13
      patients were reviewed as follows. The histological diagnosis of these cases were
      direct invasion by primary lung cancer in 13 cases, malignant tumor of the chest
      wall in 5 cases, benign tumor or inflammation of the chest wall in 4 cases, local
      recurrence of the breast cancer and post operative radiation ulcer in each 1 case
      respectively, and mediastinal peripheral nerve sheath tumor in 1 case. Full
      diagnosis of the mediastinal malignant tumors were Ewing' sarcoma,
      chondrosarcoma, malignant lymphoma, malignant fibrous histiocytoma and
      eosinophilic granuloma in each 1 case respectively. The total number of resected
      ribs was 10 (bilateral 5 ribs with sternal body) in 1 case, 4 in 1 case, 3 in 6
      cases, 2 in 2 cases and 1 in 4 cases. The following statement shows our methods
      of chest wall reconstructions. We treated one case with wide anterior chest wall
      resection, we treated by the Marlex-resin sandwich, 4 cases with 4 or 3 ribs of
      anterior or lateral chest wall, by sheets of Marlex mesh in layers, 3 cases with
      3 ribs of posterior site, 1 case with 2 ribs and 4 cases with one rib, these 7
      cases treated by cross sutures. And, we treated another 2 cases by pedicle
      omental flap and major pectoral muscle in each case respectively. The Marlex
      resin sandwich has easy fixation and excellent stability, but it has also foreign
      body reaction. Therefore our case needed to remove of sandwich 10 months later
      for cellulitis and infection after the operation. Recently we use mostly sheets
      of Marlex mesh in layers, for the reconstruction of the chest wall with 3 or more
      rib's defect, but if it is more small defect, we use the cross suture method. The
      cross suture is very easy and effective method to maintain the stability of small
      chest wall defect.

PMID- 8558804
TI  - [Indication and method of chest wall reconstruction].
AB  - Fifty two patients with chest wall resection were reviewed, with emphasis upon 16
      patient with chest wall reconstruction. The latter 16 patient consisted of 6 with
      metastatic tumor, 3 of primary lung cancer, 2 of breast cancer, one of primary
      chest wall tumor, and others. Before 1985, reconstruction after chest wall
      resection was conducted in four cases by using methyl methacrylate (Resin). One
      patient developed erosion of the overlying skin due to protrusion of the edge of
      Resin-plate with delayed wound healing. Since 1986, we have employed muscle or
      myocutaneous flap and/or Marlex mesh in reconstruction of the chest wall defect.
      Twelve patients underwent surgery in this way. Neither paradoxical movement of
      the chest wall nor respiratory distress developed in the postoperative course of
      any patient. Thirty six of fifty two patients underwent chest wall resection
      without following reconstruction as in the former group. Of them one patient of
      anterior chest wall resection developed respiratory failure. We conclude that rib
      resection involving as many as three or more in the anterior chest wall, or four
      rib resection or more in the lateral chest wall, if the area of the defect is
      greater than 100 cm2, chest wall reconstruction is indicated. Moreover, we
      believe that muscle or myocutaneous flap and/or Marlex mesh in the best way of
      reconstruct in following chest wall resection.

PMID- 8558805
TI  - [Operative corrections of funnel chest depend on age group].
AB  - The methods of correcting funnel chest are various and many. It's necessary to
      select the proper method depending on the age group. For children, sternal
      elevation by Ravitch's procedure produces to better results without prosthesis.
      For adolescent patients, the elevated sternum can be maintained by Kirschner's
      wires. Furthermore, adult patients have severe chest wall deformities with
      calcificated costal cartilage. The methods sternal elevation methods cause an
      unsatisfactory by postoperative appearance for adult patients with funnel chest.
      Two adult patients, 20 and 48-year-old men, underwent the sternal turnover
      methods with complete sternal blood supplies. The procedures of the new method
      turn over the sternal body crossing bilateral internal thoracic vessels and
      abdominal rectal muscles. No chest wall deformities were seen and the patency of
      internal thoracic arteries and superior epigastric arteries was revealed by
      postoperative arteriography.

PMID- 8558806
TI  - [Chest wall reconstruction after the resection of primary chest wall tumors].
AB  - Between April 1983 and June 1994, we performed chest wall reconstructions on 9
      patients (7 males and 2 females) out of 27 all of whom underwent the radical
      resection for the primary chest wall tumors. Histological diagnosis of tumors
      included 6 chondrosarcomas, 1 Ewing's sarcoma, 1 plasmacytoma and 1 giant cell
      tumor. Six lesions were located on the rib and 3 on the sternum. For the
      materials for reconstruction of the chest wall use a polyethylene plate in 2
      patients, a Marlex mesh in 5 patients and a Marlex mesh with a methyl
      methacrylate utilizing the sandwich method in 2 patients. The polyethylene plate
      proved to be satisfactory for maintaining stability of the chest wall. However,
      our experience using this plate showed intensive foreign body reactions, and
      discovering these we have not use the polyethylene plate. Marlex mesh had an
      affinity with human tissue and was very easy to use and produced no
      complications. We use Marlex mesh for flat surfaces on the anterior or posterior
      chest wall. Marlex mesh and methyl methacrylate utilizing the sandwich method,
      combined the solidity and shaping of methyl methacrylate with the benefit such as
      easy fixation and excellent incorporation of the mesh.

PMID- 8558807
TI  - [Reconstruction after wide resection of the chest wall: application of plates as
      rigid prosthetic materials].
AB  - Wide resection of the chest wall requires reconstruction with rigid prosthetic
      material to protect the thoracic organs and to avoid flail chest. We tried to use
      three kinds of plates for chest wall reconstruction in 4 cases: acrylic plate for
      1, ultra-high-molecular-weight polyethylene (UHMWP) plate for 1 and methyl
      metacrylic resin (MMR) plate for 2. Marlex mesh was utilized to strengthen the
      rebuilt chest wall sandwiching rigid prosthesis in UHMWP plate and MMR plate.
      Except for somewhat local accumulation of serous fluid in two cases of acrylic
      plate and MMR plate, postoperative courses were uneventful in all cases. Acrylic
      plate which was used for patient with metastatic sternal tumor was easily damaged
      by heat. UHMWP plate which was used for patient with large benign sternal tumor
      was expensive and took a long time to make. On the other hand, MMR plates which
      were used for two patients with malignant lateral chest wall tumor were easy to
      handle on the spot and not expensive. MMR plate sandwiched by Marlex mesh seems
      to be more suitable and available for chest wall reconstruction.

PMID- 8558808
TI  - [Reconstruction of chest wall defects with autogenous ribs grafts].
AB  - Three methods of chest wall reconstruction using autogenous rib grafts were
      reported. Fresh non-vascularized autogenous rib graft, vascularized autogenous
      ribs with muscle-flap, and pasteurized autogenous rib grafts were the materials
      used in these techniques. They are less convenient than those with artificial
      materials but afterwards physiologically more natural chest wall will be
      reconstructed. The third method (pasteurized rib graft) was applied to 22-year
      old female with large recurrent desmoid tumor. Six resected ribs were heated in
      the saline at 60 degrees C for 30 min. and three of them were returned to the
      former position. Though tumor cells and bacteria are killed under this condition,
      these heated bone can be revascularized and replaced by normal bone as early as
      fresh non-vascularized rib graft.

PMID- 8558809
TI  - [Chest wall reconstruction, relation between reconstruction method and
      infection].
AB  - We have operated 52 cases of chest wall resection in these 20 years. Twenty five
      cases in it were reconstructed by unabsorbable artificial materials such as
      Marlex mesh, Gore-Tex sheet and some others (Group 1). Eleven cases were covered
      with the net knitted by absorbable threads or muscle flaps (Group 2). Resting 16
      cases have not received any definitive renovations (Group 3). Group 1 has
      suffered from such severe postoperative complications as acute empyema (8%) and
      chronic empyema (8%). Few cases in Group 2 has had infectious complication and
      ventilatory disturbance. Rate of postoperative vital capacity in Group 3 was the
      lowest value among three groups, though they had the smallest chest wall defects.
      We obtained following conclusions from this study. Every chest wall defect should
      be repaired by some way even if the defect were small. Chest wall defect in
      compromised host should be repaired by absorbable artificial material and muscle
      flap. Unabsorbable artificial materials are now indispensable for the
      reconstruction of large chest wall defect, however we must fully take care of
      postoperative infections in cases of its use.

PMID- 8558810
TI  - [Chest wall reconstruction for lung cancer patient].
AB  - To prevent flail chest after chest wall resection, chest wall reconstruction was
      performed to 74 primary lung cancer patients during the period between 1975 and
      1994, out of 1,435 resected lung cancer patients, while in 29 cases, chest wall
      resection were performed without reconstruction. Numbers of ribs resected were
      from 1 to 5, mean 2.7, median 3. Chest wall reconstructions were performed in
      66.7% of the patients for 2 ribs resected cases, 83.8% for 3 ribs cases, and
      90.9% for more than 4 ribs cases. For chest wall reconstruction double layered
      Marlex mesh was used since 1982, while Dacron or Teflon felt was used until 1984.
      There was no flail chest, wound infection or operative death in the patients with
      chest wall resection and reconstruction. Survival curve of the p-T 3 N 0, 1 M 0
      received chest wall reconstruction was compatible to the stage II cases out of
      1,435 resected lung cancer patients (47.1% and 43.0% at 5 years). There is no
      need to perform chest wall reconstruction in cases like 1st to 3rd rib resection,
      or whose chest wall defect is covered with scapula. If the chest wall defect is
      lower than that and also lateral or anterior, chest wall reconstruction is
      indicated, even if resected ribs are less than 3. We should not hesitate to
      remove chest wall in order to get complete resection of the tumor, if tumor
      invasion is suspected surgically. Because we can reconstruct the chest wall with
      satisfactorily low risk of complications.

PMID- 8558811
TI  - [Homologous graft transplantation].

PMID- 8558812
TI  - [One stage operation for ischemic heart disease and abdominal aortic aneurysm
      with ascending aortic calcification].
AB  - A 69-year-old man was referred to us with the diagnosis of abdominal aortic
      aneurysm (7 cm in diameter). Additionally his coronary arteriogram showed severe
      stenosis (LMT 75% and #6 99% delay). Because his ascending aorta was calcified
      severely, double CABG (LITA to LAD and RGEA to PL) was carried out in hypothermic
      ventricular fibrillation. Abdominal aortic aneurysm was replaced thereafter while
      the patient was still on cardiopulmonary bypass. His postoperative courses was
      satisfactory. In cases requiring early operation for both myocardial ischemia and
      abdominal aortic aneurysm, one stage operation was recommended. When
      atherosclerotic changes in the ascending aorta were severe, in situ arterial
      bypass grafting for ischemic heart disease under hypothermic ventricular
      fibrillation was useful.

PMID- 8558813
TI  - [Usefulness of open lung biopsy for corrective surgery on incomplete
      atrioventricular septal defect associated with severe pulmonary hypertension and
      right to left shunting].
AB  - In congenital heart defects, it is sometimes difficult to decide the operative
      indication in patients, who has severe pulmonary hypertension (PH) and right to
      left shunting, from clinical symptoms and cardiac catheterization. We here report
      a case of incomplete atrioventricular septal defect. The patient is 9 months old
      with the Down's syndrome. The cardiac catheterization showed severe PH and right
      to left shunting. Preoperative mean pulmonary artery pressure was 75 mmHg,
      pulmonary systemic pressure to systemic pressure ratio (PP/PS) was 1.17,
      pulmonary systemic flow to systemic flow ratio (QP/QS) was 0.79, pulmonary
      systemic resistance to systemic resistance ratio (RP/RS) was 1.54 and pulmonary
      vascular resistance (PVR) was 9.6 woodunits.m2. These data suggested that the
      irreversible pulmonary vascular disease was present. However the PVR decreased
      from 9.6 to 3.6 woodunits.m2 after inspiration of 100% oxygen. We therefore
      performed open lung biopsy for further evaluation of the pulmonary vascular bed.
      The pathological findings obtained at lung biopsy indicated that there was no
      irreversible pulmonary vascular disease. This case was diagnosed suitable for a
      corrective surgery. Total repair was performed and the subsequent clinical course
      was satisfactory. We thus suggest that the open lung biopsy is useful to decide
      the surgical indication when it is difficult to determine an operative indication
      from hemodynamic measurement alone.

PMID- 8558814
TI  - [Reconstruction procedure for full-thickness chest wall defects].
AB  - Reconstruction of full-thickness chest wall defects after the total layer
      resection of the chest wall has been performed on 6 cases. Five of 6 cases had
      local recurrent of breast carcinoma, one case had a recurrent liposarcoma in the
      chest wall. The reconstruction procedure of skeletal chest wall used to double
      soft Marlex mesh. The soft tissue layer of the chest wall was reconstructed with
      myocutaneous flaps in five cases (four cases using latissimus dorsi, one case
      using rectus abdominis), with omental pedicle graft and free skin flap in one
      case. Minor wound complications occurred in 2 in the 6 cases, one case had
      myocutaneous flap using rectus abdominis, the other case using omental pedicle
      flap, but any postoperative complications including respiratory insufficiency was
      not seen with myocutaneous flap using latissimus dorsi. The latissimus dorsi
      myocutaneous flap was most suitable to cover the soft tissue layer of the chest.
      We confirmed that Marlex mesh and latissimus dorsi myocutaneous flap were able to
      reconstructed for large defects of full-thickness chest wall involving the
      sternum, there were best approach to reconstruction full-thickness chest wall
      defects after total layer chest wall resection.

PMID- 8558815
TI  - [Surgery for thoracic aortic aneurysm in the elderly patients with renal
      insufficiency and pulmonary disfunction].
AB  - Renal insufficiency and pulmonary disfunction are the major risk factors of
      surgical treatment for thoracic aortic aneurysm (TAA). The 1st case was 79-year
      old female with ruptured TAA. The 2nd case was 76-year-old female with thoraco
      abdominal aortic aneurysm. Both patients successfully treated with graft
      replacement using temporally shunt (12 mm Gore-Tex graft), tracheostomy and
      epidural analgesia.

PMID- 8558816
TI  - An investigation into the effects of solid or grid cage flooring on the welfare
      of laboratory rats.
AB  - The welfare of laboratory rats housed on either solid or grid floors was
      investigated in several ways. No differences were found in body weight gain, food
      consumption or water consumption amongst rats housed in either condition. When
      handling was standardized between the 2 groups, there was no correlation between
      flooring and docility. Preference testing revealed that rats chose to dwell on
      solid floors rather than grids, regardless of previous housing experience. This
      preference for solid floors was particularly marked (88%) when the animals were
      resting and much less marked during activity (55.4%). Since the rats were
      observed to spend 70 to 75% of their time resting, it was concluded that their
      welfare was likely to be improved by housing them on solid floors.

PMID- 8558817
TI  - Short-term evaluation of a foraging device for non-human primates.
AB  - In the USA, any institution involved in using non-human primates for research has
      had, for regulatory reasons, to address the psychological needs of these animals.
      Enriching the environment through the use of foraging devices has been one method
      and a study was designed to evaluate the short-term effect of a new foraging
      device on singly-housed cynomolgus monkeys. The study was divided into 3 one-week
      periods of observation: baseline, device filled with normal ration, and device
      filled with a novel food. Four behaviours were recorded: foraging, self-directed,
      hopper feeding, and other behaviours. During the observation periods the device
      was accepted in preference to the standard hopper style feeder and self-directed
      behaviours were significantly reduced compared with the baseline period. Changing
      to a novel food re-kindled interest in the device and reduced the extinguishing
      effect: i.e. decrease in interest or use of the device. Based on this study, the
      feeder has been included with several other devices in a rotation programme.

PMID- 8558818
TI  - Evaluation of animal welfare by the self-expression of an anxiety state.
AB  - Although mental well-being has long been accepted as an important aspect of
      animal welfare, the subjective feelings of farm or laboratory animals are
      regarded as lying beyond the scope of scientific enquiry. We now report that
      pharmacological conditioning of pigs with a drug, pentylenetetrazole, known to
      induce anxiety in man, permits investigation of the presence or absence of this
      psychological state during exposure to a variety of environmental stimuli
      encountered during normal husbandry. Such pharmacological conditioning therefore
      provides a valuable means to assess and improve elements of animal welfare and
      should be applicable to other species that show operant behaviour.

PMID- 8558819
TI  - Effects of gentling on open-field behaviour of Wistar rats in fear-evoking test
      situation.
AB  - The effect of individual gentling on open-field behaviour of adult male Wistar
      rats was studied. Dark open-field evoked prey-like behaviour both in the gentled
      and in the nonhandled rats. Escape activity dominated in both groups although
      some habituation as a function of trials occurred. The effects of gentling were
      mainly seen in the quality of the fear-reaction as a result of reduced fear of
      human contact. Parameters that differentiated the 2 groups were middle field
      ambulation, middle field rearing and passive motionlessness.

PMID- 8558820
TI  - Hereditary compulsive self-mutillating behaviour in laboratory rabbits.
AB  - During the last few years an increasing number of cases of extensive
      automutilation has been observed in a rabbit breeding colony of Checkered
      crosses. Digits and pads of the front feet were traumatized. No other behavioural
      abnormalities or signs of disease were evident. Self-mutillation was seen both in
      stock, breeding and experimental animals, in rabbits kept singly in cages and in
      those housed in groups on the ground, in rabbits kept in different buildings and
      under the care of different staff members. This behavioural abnormality of
      Checkered crosses has also been observed in animals after being placed into other
      institutions or private homes. No evidence of an agent responsible for the
      occurrence of self-injury could be found with parasitological, mycological,
      histological, clinical or haematological examination. Twelve to 16 animals are
      affected yearly in a colony varying in size between 130 and 230 rabbits.
      Following complete healing, relapses occurred up to 3 times per year, on either
      the same or the opposite front foot. In the last 21 cases episodes of
      automutillation could be regularly interrupted with the dopamine antagonist,
      haloperidol. Similar signs of auto-mutillation were never seen in animals of
      another breeding line kept in the same building and under the same conditions nor
      in animals brought in from other breeding colonies. A relatively high coefficient
      of inbreeding can be presupposed in this 15-year-old breeding colony of Checkered
      crosses. A genetic predisposition for the behavioural anomaly described appears
      very likely.

PMID- 8558821
TI  - Acquisition of a conditioned reflex in New Zealand white rabbits from three
      sources.
AB  - In studies of learning using rabbits, there has been standardization of
      behavioural procedures across laboratories. Less attention has been paid to
      variation that may arise from genetic differences and/or differences in rearing
      conditions. The present experiment revealed that acquisition of a conditioned
      reflex can be affected dramatically by such differences. Specifically, the
      acquisition of a conditioned reflex in New Zealand White (NZW) rabbits from 3
      different suppliers was compared. All rabbits received behavioural training in
      which a tone or a light signalled an electrotactile stimulation of the trigeminal
      nerve near the rabbits' right eye. This tactile stimulus reliably elicited an
      eyeblink. Repeated presentations of the auditory and visual signals followed by
      the tactile stimulus yielded the acquisition of a conditioned response (CR),
      namely closure of the eyelids during the warning period provided by the signal
      stimuli. Two of the groups showed steady CR acquisition at a rate that matched
      previous results in other laboratories as well as in the senior author's
      laboratory. However, the third group of rabbits showed very slow acquisition, and
      some rabbits failed to show any CR acquisition.

PMID- 8558822
TI  - Midazolam in combination with fentanyl/fluanisone and nitrous oxide as
      anaesthesia in rabbits--cardiovascular parameters.
AB  - When establishing a rabbit model for cardiovascular research in our laboratory we
      have used midazolam in combination with fentanyl/fluanisone (MFF) and nitrous
      oxide as anaesthesia. In this study we focused on the effect of the anaesthetic
      regimen on cardiovascular parameters during open-chest surgery in 12 rabbits.
      Rabbits were tranquillized by intramuscular injection of fentanyl/fluanisone (0.2
      ml/kg of the drug that contained 10 mg/ml fentanyl and 0.2 mg/ml fluanisone).
      After an intraperitoneal injection of midazolam (4 mg/kg) and additional i.m.
      injection of fentanyl/fluanisone (0.1 ml/kg) the rabbits were tracheotomized and
      ventilated on a respirator delivering a gas mixture of 50% N2O, 47.5% O2, and
      2.5% CO2. The femoral vein and artery were cannulated and then rabbits received a
      supply of MFF intravenously. The chest was opened by midline sternotomy and the
      left ventricle was instrumented with piezo-electric crystals for measurement of
      regional left ventricular function and with a pressure catheter to measure left
      ventricular pressure. Radiolabelled microspheres were used to assess cardiac
      output and left ventricular tissue blood flow. Blood gas analysis showed no
      difference in the values of pH, pCO2 and pO2 between the open-chest and the
      closed-chest states. Mean aortic pressure was 74 +/- 4 mmHg in the closed-chest
      state and 65 +/- 4 mmHg in the open-chest state. Tissue blood flow showed that
      the left ventricle was well perfused, and mean tissue blood flow values varied
      between 1.80 and 2.36 ml/min.g. We conclude that the anaesthetic regimen used is
      easy to control. It is well tolerated in rabbits and is suitable for studies on
      myocardial contraction in rabbits.

PMID- 8558823
TI  - An anaesthetic mask for use on guinea pigs (Cavia porcellus) in a stereotaxic
      frame: technical note.
AB  - A mask was designed to allow inhalation anaesthesia to be used on guinea pigs
      (Cavia porcellus) whilst placed in a stereotaxic frame. To date, anaesthesia has
      been maintained in approximately 60 animals using this method, with no
      mortalities.

PMID- 8558824
TI  - Tracheoesophageal anastomosis, continent gastrostomy and oesophagostomy--a new
      experimental model in minipiglets.
AB  - Tracheoesophageal fistulae endanger newborn children by aspiration pneumonia. An
      animal model of this dangerous malformation was thought to be impossible until
      now. By tracheoesophageal anastomosis, occlusion of the oesophagogastral
      junction, proximal cervical oesophagostomy and continent gastrostomy in 25
      minipiglets a reliable model of tracheoesophageal fistula has been developed.
      After establishing the model in a pilot study the mortality following the
      establishment of this procedure was 5.6% and the minipiglets survived in
      excellent condition for 2-10 week periods under complete alimentary restriction
      and gastrostomy feeding. Therefore the method seems to be suitable for long-term
      investigations on major oesophagotracheal surgery.

PMID- 8558825
TI  - A new rat model for studying the calpain-calpastatin system.
AB  - A recombinant rat strain--Milan low-calpastatin strain (MLCS)--was derived from
      Milan hypertensive (MHS/Gib) and Milan normotensive (MNS/Gib) strains. The MLCS
      rats have normal blood pressure and low calpastatin activity, and this strain is
      proposed as a model for studies of the calpain-calpastatin system, which is
      involved in important cellular mechanisms. Calpastatin polymorphism was observed
      in 10 different strains of laboratory rats and a single locus hypothesis is
      suggested as the mode of inheritance.

PMID- 8558826
TI  - The cerebral function monitor (CFM) is a useful addition to a bilateral carotid
      artery, vein graft model.
AB  - Following human coronary artery bypass surgery, vein graft occlusion is a major
      cause of morbidity and mortality. An agent is required which will reduce the
      incidence of early graft thrombosis without causing systemic bleeding. To assess
      the efficacy of such agents a suitable experimental vein-graft model is required.
      A porcine, unilateral saphenous vein-carotid artery bypass graft model has been
      described previously, although to assess the effect of locally applied
      anticoagulant drugs, insertion of grafts bilaterally would be advantageous,
      allowing treated and control grafts to be implanted in the same animal which
      would then act as its own control. Pigs are reported as having an excellent
      collateral cerebral circulation and hence in theory, would be suitable animals to
      use as a bilateral carotid vein-graft model. This paper describes the occurrence
      of serious neurological complications during the development of such a model and
      suggests that by using a cerebral function monitor, detection of critical
      reductions in cerebral perfusion can be made early and remedial action take.

PMID- 8558828
TI  - Direct determination of saturable and non-saturable calcium uptake in the
      developing rat duodenum.
AB  - Significant changes in saturable and non-saturable intestinal calcium uptake
      processes occur during development of the rat. A modified 'free floating disc'
      assay was used to measure total, active and passive duodenal calcium uptake on
      matching duodenal segments from male Sprague Dawley rats aged 14 to 56 days of
      age. The results were compared and found to give patterns similar to data
      published for the in situ ligated loop technique.

PMID- 8558827
TI  - Choice of vehicle for three-month continuous intravenous toxicology studies in
      the rat: 0.9% saline versus 5% glucose.
AB  - A study to assess the toxic potential of a candidate-drug administered to
      unrestrained rats as 1-h infusions thrice daily for 3 months, using 5% glucose as
      vehicle, had to be aborted on day 34 because of poor physical status and
      mortalities in all groups, including controls receiving the vehicle alone.
      Investigation demonstrated an opportunistic infection, probably secondary to the
      glucose present in the intravenous formulation. A second study using 0.9% saline
      solution as a vehicle, was successfully completed.

PMID- 8558829
TI  - Non-phenotypic detection of osteopetrotic (op/op) mutation by using PCR-SSCP
      analysis.
AB  - Mice homozygous for recessive mutation osteopetrosis (op/op) on chromosome 3
      provide a unique model to study the mechanism of haematopoiesis in conjunction
      with bone formation. Based on the DNA sequence data recently reported, we
      established a PCR-SSCP (polymerase chain reaction--single strand conformation
      polymorphism) assay which identifies an amplified fragment having an insertional
      point mutation present in macrophage colony-stimulating factor (M-CSF) gene of
      op/op mice. With this assay, three genotypes, op/op, +/op, and +/+ can be
      distinguished. Although heterozygous (+/op) and normal (+/+) mice could not be
      discriminated phenotypically, we could generate op/op mutant mice starting from a
      single heterozygous (+/op) mouse using only the PCR-SSCP aided screening method.
      This assay will permit introduction of the op mutant into any strain to generate
      a new animal model to study the cytokine network and haematopoiesis.

PMID- 8558830
TI  - Rapid genotyping of low density lipoprotein receptor knockout mice using a
      polymerase chain reaction technique.
AB  - A new method for the rapid genotyping of low density lipoprotein receptor
      knockout mice is described. This method using a polymerase chain reaction (PCR)
      technique may be performed on small tissue biopsies, and represents a significant
      advantage in time over conventional genotyping by Southern blot analyses.

PMID- 8558831
TI  - Practical aspects of milk collection in the rat.
AB  - It is a requirement as part of the safety evaluation of novel compounds, which
      are intended to be administered to pregnant women or women with young children,
      that the potential for the compound or its metabolites to be transferred from a
      dam to its litter during lactation is measured. The data obtained from the rat
      milking studies are also used to support the rat peri- and post-natal studies.
      Therefore it is necessary to collect multiple milk samples from lactating rats.
      In this paper it was decided to concentrate on three areas: 1. The factors which
      had to be considered during the development of the rat milking technique; 2. The
      outline of the basic study design for a rat milking study; 3. The technique for
      milking rats.

PMID- 8558832
TI  - Black scorpion (Heterometrus longimanus) as a laboratory animal: maintenance of a
      colony of scorpion for milking of venom for research, using a restraining device.
AB  - Scorpion venom is a rich source of many proteins and peptides. A method for
      collection of venom from scorpions using a restraining device is being described.
      The details and measurement of the restraining device as well as that of the
      current used are described.

PMID- 8558833
TI  - Spleen pigmentation in young C57BL mice is caused by accumulation of melanin.
AB  - It has been previously reported that in 2 C57BL mouse sublines a dark
      pigmentation of the cranial part of the spleen occurs in up to 30% of the animals
      within the populations. It was not clear whether this discoloration is caused by
      melanosis, lipofuscinosis or haemosiderosis. With the use of light and electron
      microscopy of stained spleen sections, we identified the pigment in 14 out of 60
      C57BL mice aged 8-10 wks. In the mice with pigmented spleens there was
      accumulation of melanin, predominantly in melanophores. Literature data indicate
      that apart from melanin, lipofuscin and haemosiderin can be observed in splenic
      macrophages provided that the mice are older than those studied by us. We
      conclude that melanin is the principal pigment causing spleen discoloration in
      young C57BL mice. Splenic melanosis displays inter-individual variation, but its
      relevance from a pathophysiological point of view remains obscure.

PMID- 8558834
TI  - Spontaneous rhabdomyosarcomas in aged Mastomys (Praomys coucha).
AB  - Two spontaneous tumours in the hind leg of 2 aged Mastomys were diagnosed as
      poorly differentiated rhabdomyosarcomas. In both cases, the neoplastic cells had
      no evidence of cross-striation, but had a positive reaction for muscle-specific
      proteins. This is the second report of rhabdomyosarcomas in Mastomys, and the
      first described in detail.

PMID- 8558835
TI  - Helicobacter pylori and gastric mucosal cytokines: evidence that CagA-positive
      strains are more virulent.

PMID- 8558836
TI  - New concepts in the pathogenesis of drug-induced lupus.
AB  - Although the importance of DNA methylation in normal cellular development and
      hereditary disease states has been appreciated for some time, the role of
      environmental agents in causing DNA methylation abnormalities and the effects of
      DNA hypomethylation on T cells have only recently been examined. This review
      summarizes current knowledge about the role of DNA methylation in regulating T
      function and gene expression and highlights a novel mechanism causing
      autoimmunity, in which epigenetic modification of T cell DNA by environmental
      agents plays an important role in triggering lupus-like diseases. The
      observations that DNA methylation inhibitors modify gene expression and induce
      autoreactivity in cloned, Ag-specific CD4+ cells in vitro, that the modified
      cells cause autoimmunity in vivo, and that similar changes are found in patients
      with active lupus provide a new approach to understanding how some forms of
      autoimmunity develop and may lead to new and more effective treatments.

PMID- 8558837
TI  - Heightened inflammatory response and cytokine expression in vivo to cagA+
      Helicobacter pylori strains.
AB  - BACKGROUND: Helicobacter pylori strains that possess the cytotoxin-associated
      gene (cagA) are highly associated with peptic ulcer disease, but the role of cagA
      in pathogenesis is unknown. EXPERIMENTAL DESIGN: To test the hypothesis that
      cagA+ stains elicit a greater proinflammatory cytokine response in the gastric
      mucosa than cagA- strains, gastric biopsies were obtained from 52 patients and
      studied by histology, culture, enzyme-linked immunosorbent assay, and reverse
      transcription polymerase chain reaction. RESULTS: Of 52 patients, 32 (62%) were
      infected with H. pylori based upon both serology and histology or culture, 16
      (31%) were negative by serology, histology, and culture, and four (7%) were
      positive by serology only. Of 15 H. pylori-infected patients with peptic
      ulceration, 14 (92%) were infected with cagA+ strains compared with 8 (50%) of 16
      patients with gastritis alone, and those infected with cagA+ strains had
      significantly higher grades of inflammation in the gastric mucosa. Antral
      inflammation score was significantly associated with IL-8 production. Antral
      biopsies from infected patients, compared with uninfected patients, significantly
      more often demonstrated IL-1 beta, IL-2, and IL-8 expression, and those infected
      with cagA+ compared with cagA- strains significantly more often expressed IL-1
      alpha and IL-1 beta and showed elevated antral IL-8 protein levels. Similarly,
      patients with ulcer disease significantly more often expressed antral IL-1 alpha
      and IL-8 than those without ulceration. CONCLUSION: These results indicate that
      infection with cagA+ H. pylori strains is associated with higher grades of
      gastric inflammation, correlating with enhanced mucosal levels of IL-8, and
      increased risk of peptic ulceration.

PMID- 8558838
TI  - Myocyte nuclear mitotic division and programmed myocyte cell death characterize
      the cardiac myopathy induced by rapid ventricular pacing in dogs.
AB  - BACKGROUND: Observations in humans have raised the possibility that idiopathic
      dilated cardiomyopathy is characterized by myocyte cell loss and cell
      proliferation, which contribute to wall thinning and chamber dilation. Moreover,
      the mechanism of myocyte cell death in this patient population has been unclear.
      Because rapid ventricular pacing in dogs leads to a dilated myopathy that mimics
      the idiopathic form in man, this animal model was used to demonstrate whether
      myocyte nuclear mitotic division and programmed myocyte cell death occur in this
      setting. Additionally, the expression of proliferating cell nuclear antigen
      (PCNA) and Fas protein in myocytes was examined as a molecular indicator of the
      activation of the cell cycle and apoptotic cell death, respectively. EXPERIMENTAL
      DESIGN: Mongrel dogs were chronically instrumented for measurements of systemic
      hemodynamics and for left ventricular pacing. At sacrifice, myocardial samples
      were obtained for the estimation of the number of myocytes and interstitial cells
      showing mitosis and for the detection of DNA laddering. In addition, the number
      of myocyte nuclei exhibiting DNA strand breaks, as well as the frequency of
      myocytes labeled by PCNA and Fas protein, was determined. Finally, the
      distribution of nuclei in enzymatically dissociated myocytes was evaluated.
      RESULTS: Pacing-induced heart failure was characterized by DNA fragmentation and
      by 3700 myocytes per million cells undergoing apoptotic cell death. This
      phenomenon was accompanied by 11,000 cells per million expressing Fas protein.
      Concurrently, 22 and 17 myocytes and interstitial cells per million showed
      nuclear mitotic division, whereas no changes in the relative proportions of
      mononucleated and multinucleated myocytes were detected. Moreover, PCNA-labeled
      myocytes accounted for 40,000 cells per million. CONCLUSIONS: In conclusion, the
      induction of PCNA and Fas may be linked to the activation of myocyte
      proliferation and programmed cell death in the myocardium with rapid ventricular
      pacing, and these two cellular responses may play a key role in the development
      of the congestive dilated myopathy.

PMID- 8558839
TI  - Chronic administration of epidermal growth factor to pigs induces growth,
      especially of the urinary tract with accumulation of epithelial glycoconjugates.
AB  - BACKGROUND: Epidermal growth factor (EGF) receptor hyperstimulation induced by
      systemically administered EGF or by the development of transgenic mice
      overexpressing transforming growth factor alpha (TGF alpha) or other EGF-related
      ligands is known to induce various effects, such as acceleration of developmental
      processes like incisor eruption, inhibition of gastric acid secretion,
      morphologic changes in the pancreas resembling pancreatitis, and malignancies in
      mammary glands and the liver. The present investigation was initiated to explore
      the effects of systemic EGF administration to the mature organism in a species
      with greater anatomic resemblance to humans than rodents. EXPERIMENTAL DESIGN:
      Eleven Goettingen Minipigs underwent 4 weeks of treatment either with placebo (n
      = 5) or human recombinant EGF 30 micrograms/kg/day (n = 6) administered
      subcutaneously. At the end of Week 4, the animals were sacrificed, autopsy was
      performed, and tissue samples were collected for histologic examination. RESULTS:
      EGF treatment caused macroscopic enlargement of the ureters, kidney, and heart.
      The ureters increased 4-fold in cross sectional area due to growth of all wall
      layers. The urothelium was hyperplastic with intracellular accumulations of
      material staining with Periodic acid-Schiff. Similar but less pronounced changes
      were found in the pancreas, lungs, salivary glands and esophagus. CONCLUSIONS:
      The most important observation of the present study is that systemic treatment
      with EGF for 4 weeks induces considerable growth to the urinary tract. We suggest
      new biologic effects of the EGF family in promoting growth of the urinary tract
      and in stimulating epithelial glycoconjugate biosynthesis in the urothelium and
      excretory ducts of the pancreas.

PMID- 8558840
TI  - FK506 nephrotoxicity: morphologic and physiologic characterization of a rat
      model.
AB  - BACKGROUND: FK506 is a useful agent in the prevention of allograft rejection but
      has recently been shown to be nephrotoxic. EXPERIMENTAL DESIGN: Sprague-Dawley
      rats (n = 40) were divided into four groups: control (C); low-salt (LS); FK506, 3
      mg/kg daily by gavage (FK); and FK506-low-salt (FK-LS). After 6 weeks, the
      animals underwent physiologic studies and were sacrificed with perfusion fixation
      of the kidneys. Semiquantitative analysis of morphologic injury was performed as
      well as grading of juxtaglomerular apparatus (JGA) granularity (1-micron plastic
      sections). Computer-assisted morphometry was used to measure medullary thick
      ascending limb (mTAL) size within the inner stripe. RESULTS: Serum creatinine and
      plasma renin activity were significantly elevated only in the FK-LS group, but
      both FK groups had significantly increased fractional excretion of Mg. Tubular
      atrophy and fibrosis involving medullary rays and inner stripe (areas of low
      oxygen availability) was minimally present in FK, but prominent in FK-LS (P <
      0.001). Injury correlated with decreased function (P < 0.001). Variance of mTAL
      size, an expression of co-existent tubular atrophy and hypertrophy was
      significantly greater in FK-LS and correlated with decreased renal function and
      urine osmolality (P < 0.001). JGA granularity was increased by FK506 (P < 0.006)
      with the highest values in FK-LS (P < 0.001), and strongly correlated with injury
      (P < 0.001). JGA granularity did not correlate with circulating renin activity
      levels, suggesting local activation of a renin-angiotensin system. CONCLUSIONS:
      FK506 compromises renal parenchymal zones which are known to have limited oxygen
      availability (medullary ray and inner stripe), a pattern that has been observed
      with other nephrotoxins. The injury is potentiated by salt depletion and may be
      mediated by the renin-angiotensin system. Furthermore, these findings illustrate
      the close correlation between the medullary injury that was observed and the
      impaired function that was documented.

PMID- 8558841
TI  - Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine
      of patients with lupus nephritis.
AB  - BACKGROUND: In patients with lupus nephritis, mononuclear inflammatory cells
      infiltrate the renal interstitium and glomeruli, and the degree of leukocyte
      infiltration correlates with the severity of the renal dysfunction. The precise
      mediator signaling inflammatory cells to migrate into the kidney is not known.
      Recent findings that monocyte chemoattractant protein-1 (MCP-1), a chemotactic
      cytokine with a high degree of specificity for lymphocytes and monocytes, is
      overexpressed in glomeruli from rats with immunecomplex glomerulonephritis
      prompted us to explore the possibility that MCP-1 could be implicated in the
      renal inflammatory response of lupus erythematosus. EXPERIMENTAL DESIGN: Serum
      and urine levels of MCP-1 were evaluated in 10 patients with active lupus
      nephritis. Patients were studied at admission, before therapy, and at various
      time points after the first administration of high dose methylprednisolone. There
      was an additional observation of the four patients who underwent remission of
      clinical signs of the disease after chronic steroid treatment. Three additional
      groups, one (n = 9) of patients with inactive lupus nephritis, one (n = 9) of
      patients with nonlupus glomerulonephritis and high degree proteinuria, and one (n
      = 10) of healthy subjects, were also studied. RESULTS: In patients with active
      lupus nephritis, urinary MCP-1 was significantly higher than in lupus patients
      studied in the inactive phase of the disease or in healthy volunteers. High doses
      of i.v. methylprednisolone significantly lowered urinary MCP-1 in patients with
      active lupus nephritis. In patients undergoing remission of lupus nephritis after
      chronic steroid treatment, urinary MCP-1 did not correlate with either serum MCP
      1 levels or proteinuria. Unlike in lupus, in patients with nonlupus forms of
      glomerulonephritis, urinary MCP-1 was comparable to controls. CONCLUSIONS:
      Altogether, the present data suggest a role for MCP-1 in mononuclear cell
      migration into the kidney in lupus nephritis.

PMID- 8558842
TI  - Biochemical interaction between Tamm-Horsfall glycoprotein and Ig light chains in
      the pathogenesis of cast nephropathy.
AB  - BACKGROUND: Cast nephropathy in multiple myeloma patients is caused by
      heterotypic aggregation of Tamm-Horsfall glycoprotein (THP) with monoclonal light
      chains (Bence Jones protein, BJP). Co-aggregation of these proteins is triggered
      by the binding of BJP to a specific peptide portion of THP. Defining those
      factors that alter the interaction between BJP and THP may help to understand
      further the pathogenesis of cast nephropathy and serve to decrease the morbidity
      and mortality of cast nephropathy. We hypothesized that pH, calcium, furosemide,
      and the carbohydrate moiety of THP all modulate the protein-protein interaction
      between BJP and THP. EXPERIMENTAL DESIGN: Binding affinity and aggregation rate
      of human THP with two human nephrotoxic BJP were tested at pH 8.5, 7.4, and 5.0.
      The effects of calcium, furosemide, and free sialic acid were also evaluated.
      Binding and aggregation of BJP with THP purified from normal volunteers treated
      with oral colchicine were observed. The carbohydrate components of THP were also
      analyzed. RESULTS: An acidic environment increased initial binding rate and
      produced a parallel increase in the aggregation rate of THP with BJP. Calcium and
      furosemide enhanced aggregation rates without interfering with binding.
      Colchicine treatment decreased the amount of sialic acid linked alpha(2-6) to
      galactose (NeuAc alpha 2-6Gal) and sialic acid linked alpha(2-3) to galactose
      (NeuAc alpha 2-3Gal) on THP and thereby decreased the aggregation rate with BJP
      without altering binding. Addition of free sialic acid did not alter binding but
      did decrease aggregation rates of the two proteins. CONCLUSIONS: Environmental
      conditions modulate BJP-THP interactions and may be responsible for inducing case
      nephropathy in multiple myeloma. Modification of carbohydrate components of THP
      or use of oligosaccharides may decrease or prevent cast nephropathy.

PMID- 8558843
TI  - Critical role of extracellular matrix on induction by phenobarbital of cytochrome
      P450 2B1/2 in primary cultures of adult rat hepatocytes.
AB  - BACKGROUND: Although it has been known for more than three decades that
      administration of lipophilic chemicals, including phenobarbital, produces liver
      hypertrophy, proliferation of smooth endoplasmic reticulum, and induction of
      liver microsomal enzymes such as cytochromes P450 (CYP) 2B1 and 2B2, the
      mechanism of this adaptive response remains largely unknown. An important advance
      was the recognition that, unlike cultures of continuously proliferating liver
      cell lines or cultures of primary non-proliferating adult rat hepatocytes
      maintained on either plastic or collagen-coated dishes, hepatocytes cultured on a
      basement membrane gel, Matrigel, formed rounded clusters and permitted
      phenobarbital-mediated induction in vitro of CYP 2B1/2 mRNAs and immunoreactive
      proteins (1). EXPERIMENTAL DESIGN AND RESULTS: We cultured adult rat hepatocytes
      on Type 1 collagen (Vitrogen) and allowed the cells to spread, flatten, and
      firmly attach to the substratum. Subsequent incubation in medium containing
      Matrigel as a soluble component, fully restored, in a dose-dependent manner, the
      ability to respond to phenobarbital with induction of CYP 2B1/2 mRNAs. Repeating
      this experiment with medium containing equivalent amounts of purified laminin, a
      major component of Matrigel, or with YIGSR or SIKVAV, two peptides known to mimic
      various activities of laminin, similarly restored phenobarbital responsiveness to
      hepatocytes cultured on Vitrogen. In contrast, use of equal amounts of SHA-23, a
      scrambled peptide relevant to SIKVAV, produced no such effect. None of these
      treatments caused a rounding or any other observable change in the flattened,
      cellular morphology, making it unlikely that cell-spreading or alterations in
      cell shape account for loss of such differentiated liver functions as
      phenobarbital induction of CYP 2B1/2 mRNAs in cultured hepatocytes on Vitrogen.
      Hepatocytes cultured on Matrigel in the presence of either colchicine,
      cytochalasins B and D, nocodazole, or taxol did not show induction of 2B1/2 mRNAs
      by phenobarbital specifically, while the amounts of both albumin and glucose-6
      phosphate dehydrogenase (G6PD) mRNAs were unaffected. CONCLUSIONS: We conclude
      that the process by which phenobarbital induced 2B1/2 mRNAs in hepatocytes
      appears to require highly concerted effects of specific extracellular components
      prominently involving laminin. This likely occurs through a signal transduction
      process requiring probably both microfilament and microtubular integrity.

PMID- 8558845
TI  - Comparison of P53 protein overexpression with P53 mutation in bladder cancer:
      clinical and biologic aspects.
AB  - BACKGROUND: Alterations of the tumor suppressor gene p53 are known to occur in
      bladder cancer. Although p53 overexpression is associated with mutation of the
      p53 gene, a substantial discrepancy between molecular genetic alteration in p53
      and overexpression of the protein has been found. EXPERIMENTAL DESIGN: Tumor
      specimens of 39 bladder cancer patients were immunohistochemically analyzed for
      p53 overexpression, and the results were compared with the presence of a mutation
      as assessed by single strand conformation polymorphism (SSCP) and direct
      sequencing. Both clinical and biologic aspects were studied. RESULTS: A
      significant correlation between p53 overexpression and poor survival in the whole
      group studied was found (p < 0.01). No association between p53 overexpression and
      decreased survival was found for invasive tumors in contrast with other studies.
      Differences in treatment of the patients and different Ab and scoring systems
      used might explain these differences. In our study, the Kaplar-Meier curves
      showed the same result for p53 overexpression and p53 mutation when the whole
      group and the invasive tumors were studied. However, in the group of superficial
      tumors, which was unfortunately too small for statistical analysis, we found p53
      overexpression in three tumors, and no p53 mutations were found. A good
      concordance between p53 mutation and p53 overexpression was found (p < 0.02).
      However, two out of eight tumors with an SSCP-proven p53 mutation showed no p53
      immunoreactivity, probably as a result of loss of the nuclear localization
      signal. Twenty three percent (7/31) of the tumors showed p53 overexpression
      without any sign of a mutation. CONCLUSIONS: Our results indicate that, despite
      good concordance between p53 mutation and p53 overexpression, there is no direct
      casual relationship between mutation and protein accumulation. Apparently, other
      events than mutation can trigger p53 stability.

PMID- 8558844
TI  - Expression of cystic fibrosis transmembrane conductance regulator in human
      gallbladder epithelial cells.
AB  - BACKGROUND: Hepatobiliary complications in cystic fibrosis result predominantly
      from lesions of the biliary epithelium. These abnormalities affect the
      intrahepatic as well as extrahepatic bile ducts and the gallbladder. The protein
      cystic fibrosis transmembrane conductance regulator (CFTR), the gene product
      defective in cystic fibrosis, functions as a cAMP-activated chloride channel in
      the plasma membrane. As such, it may represent an important driving force for
      fluid transport across the epithelium. EXPERIMENTAL DESIGN: The purpose of this
      study was to investigate the expression of CFTR in human gallbladder epithelial
      cells and to examine the chloride ion transport properties of these cells.
      Immunolocalization was performed on tissue sections. The reverse transcription
      PCR was used to analyze the expression of CFTR mRNA in freshly isolated and
      cultured gallbladder epithelial cells. The CFTR protein was detected by Western
      blotting and immunoprecipitation. The chloride ion transport properties of the
      cells were determined by 36Cl efflux studies. RESULTS: The CFTR protein was
      immunodetected in human gallbladder in situ and localized predominantly to the
      apical membrane of epithelial cells. High levels of CFTR mRNA and protein were
      maintained in gallbladder epithelial cells in primary cultured. Glycosylated
      forms of CFTR were present as confirmed by treatment with N-glycanase. Chloride
      efflux was stimulated by Ca(++)-dependent pathways but more intensely by cAMP
      dependent pathways. Stimulation of chloride efflux by agonist of the cAMP-pathway
      was inhibited by diphenylamine carboxylic acid, a chloride channel blocker. Two
      physiologically active peptides--acting via cAMP, vasoactive intestinal peptide,
      and secretin--also stimulated chloride efflux in vitro. CONCLUSIONS: Our results
      are consistent with a high expression of endogenous functional CFTR protein in
      human gallbladder epithelial cells. Physiologically active peptides, vasoactive
      intestinal peptide and secretin, stimulate chloride conductance in these cells.
      These findings indicate that CFTR play an important role in the pathophysiology
      of the biliary epithelium, including the gallbladder epithelium.

PMID- 8558846
TI  - Endothelial cell proliferation in prostatic carcinoma and prostatic hyperplasia:
      correlation with Gleason's score, microvessel density, and epithelial cell
      proliferation.
AB  - BACKGROUND: Tumor angiogenesis is necessary for tumor growth and metastasis, and
      increasing intratumoral microvessel density (MVD) in prostate carcinoma has been
      shown in several studies to be associated with increasing tumor stage. But, the
      relationships of endothelial cell proliferation to intratumoral MVD, tumor cell
      proliferation, and Gleason's score remain unknown in prostate carcinoma.
      EXPERIMENTAL DESIGN: Using a double-immunolabeling technique (paraffin-reactive
      MIB1 Ab to determine Ki67 labeling index (Ki67LI) and anti-CD34 to quantify
      microvessels), we immunostained 20 prostatic carcinomas and adjacent benign
      prostate hyperplasia (BH) and four cases of trauma-induced granulation tissue. We
      correlated intratumoral endothelial cell proliferation with intratumoral MVD,
      tumor cell proliferation, and Gleason's score, and we compared these measurements
      with endothelial cell proliferation, MVD, and epithelial cell proliferation in
      adjacent BH. RESULTS: The intratumoral endothelial cell proliferation index (mean
      0.15%) and intratumoral MVD measured 30-fold (p = 0.00007) and 1.9-fold (p =
      0.000003) greater than that of adjacent BH, respectively. However, the
      intratumoral endothelial cell proliferation index did not correlate with
      intratumoral MVD, tumor cell proliferation, or Gleason's score. Nor did
      intratumoral MVD correlate with tumor cell proliferation. In comparison, the mean
      MVD and endothelial cell proliferation rates in granulation tissue were 199 and
      6.50%, respectively, the latter 43-fold greater than the mean intratumoral
      endothelial cell proliferation index (p = 0.00023). CONCLUSIONS: Endothelial
      cells are actively proliferating in prostatic carcinoma, and their proliferation
      appears independent of intratumoral MVD and tumor cell proliferation. Yet, the
      relatively low intratumoral hyperplasia, suggests that endothelial cell migration
      and capillary remodeling play an important role in neovascularization of
      prostatic carcinoma, especially when compared with granulation tissue, which
      showed a 43-fold greater endothelial cell proliferation index. Moreover, the lack
      of correlation of intratumoral endothelial cell proliferation and intratumoral
      MVD with tumor cell proliferation suggests that tumor angiogenesis and tumor-cell
      proliferation are regulated by different mechanisms.

PMID- 8558847
TI  - Age-dependent injury in human umbilical vein endothelial cells: relationship to
      apoptosis and correlation with a lack of A20 expression.
AB  - BACKGROUND: It has recently been shown that human umbilical vein endothelial
      cells (HUVEC) become increasingly sensitive to growth factor deprivation,
      resulting in cell death, as a function of age in culture. The overall goal of the
      present study was to investigate the mechanism of lethal injury in these cells
      and compare the injury process to other known mechanisms of injury in the same
      cells. EXPERIMENTAL DESIGN: HUVEC were established in culture and maintained for
      four passages. Injury to first-passage cells and fourth-passage cells were
      examined for injury in the presence of agents that are known to confer resistance
      to apoptosis. Ultrastructural features of injury and DNA fragmentation patterns
      were assessed. Expression of factors that are known to be associated with
      resistance to apoptosis in other models were assessed. RESULTS: Fourth-passage
      HUVEC undergoing injury exhibited morphologic features characteristic of
      apoptosis and DNA fragmentation. Agents known to inhibit apoptotic cell injury in
      other models inhibited injury. A20 expression was correlated with resistance to
      injury in fourth-passage HUVEC, but there was no correlation between bcl-2 and
      bcl-x expression and resistance to injury. CONCLUSIONS: HUVEC injury resulting
      from growth factor deprivation increases as a function of age in vitro and
      appears to be a form of apoptosis. A20 expression may confer resistance to cell
      injury through this pathway.

PMID- 8558848
TI  - Expression of vascular endothelial growth factor and its receptor mRNA in
      angiosarcoma.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF), a specific mitogen for
      endothelial cells in vitro, can be angiogenic factor in vivo. VEGF is known to be
      produced by several tumor cells and plays an important role for
      neovascularization in tumor tissue. Recently, tyrosine kinase encoded by the flt
      gene was identified as a receptor for VEGF. Angiosarcoma (AS) is a rare malignant
      tumor that arises from endothelium. At present, little is known about a mechanism
      of proliferation of the AS. EXPERIMENTAL DESIGN: In an immunohistochemical study
      of 99 cases of AS, 11 cases showing a positive reaction for anti-VEGF Ab were
      selected for the present study. In these cases, expression of VEGF and its
      receptor (flt) mRNA was examined by in situ hybridization: sense and antisense
      probes for VEGF and flt mRNA were used. RESULTS: In situ hybridization study with
      antisense probes revealed that the VEGF mRNA was expressed in AS cells and
      mononuclear cells in all but one case. Intensity of VEGF staining by
      immunohistochemistry correlated well with VEGF mRNA expression. The flt mRNA was
      expressed in AS cells in all 10 cases that were positive for VEGF mRNA. Sense
      probe for VEGF and flt mRNA gave no positive reactions. CONCLUSIONS: These
      findings suggest a presence of paracrine or autocrine mechanism of proliferation
      in AS through VEGF and its receptor flt.

PMID- 8558849
TI  - Widespread expression of the parathyroid hormone-related peptide and PTH/PTHrP
      receptor genes in intestinal epithelial cells.
AB  - BACKGROUND: This study was designed to determine whether the genes for both
      parathyroid hormone-related peptide (PTHrP) and its receptor were expressed in
      close proximity to one another in various regions of the gut and whether they
      both were evident in two intestinal epithelial cell lines. The findings would
      test the idea that PTHrP acts as an autocrine or paracrine factor in the gut.
      EXPERIMENTAL DESIGN: Reverse transcription/PCR and Northern analysis were used to
      detect mRNA for PTHrP and its receptor in various regions of the normal rat gut,
      in epithelial cell populations isolated along the villus tip-crypt axis in rat
      jejunum, and in a rat and a human gastrointestinal epithelial cell line (IEC-6
      and LoVo, respectively). Antisera to PTHrP also were used to detect the peptide
      in rat gastrointestinal tissues or in growth medium from cultured cells. RESULTS:
      Both PTHrP and PTHrP receptor mRNA were found in all regions of the rat gut, in
      all cell populations isolated from rat jejunum, and in the rat and human cell
      lines. Immunoreactive PTHrP in tissue sections was observed in rat jejunal
      epithelial cells all along the villus but not in crypt cells, and immunoreactive
      peptide was found in growth medium from the cultured intestinal epithelial cells.
      CONCLUSIONS: The results show that genes for PTHrP and its receptor are expressed
      widely in gut epithelia. Expression of the two genes in the same regions of the
      gut and in the same cell line implies a local autocrine/paracrine action of the
      peptide. Expression of the peptide in villus epithelium but not in crypt cells
      suggests a role in differentiating gastrointestinal epithelial cells.

PMID- 8558850
TI  - Cryptococcus neoformans survive and replicate in human microglia.
AB  - BACKGROUND: Cryptococcus neoformans (CN) is an opportunistic pathogen that can
      cause fatal meningoencephalitis in patients with immune deficiency. Among the
      central nervous system (CNS) cells that are infected by CN are perivascular
      microglia and macrophages. Little is known about the interaction of CN and CNS
      phagocytes at the cellular level. EXPERIMENTAL DESIGN: To better understand the
      fate of CN in microglia, we followed Ab-opsonized CN in human fetal microglial
      culture by phase-contrast microscopy, combined lighted microscopy and
      transmission electron microscopy of plastic-embedded monolayers, and
      immunocytochemistry for localization of capsular Ag. RESULTS: Phase-contrast
      microscopy revealed that microglia initially internalized and contained Ab
      opsonized yeast cells within phagolysosomes. However, CN escaped from microglia
      and resumed extracellular growth 16 to 24 hours after being phagocytosed.
      Transmission electron microscopy/1-mu epoxy sections revealed that intracellular
      CN were localized in two types of phagosomes in microglia: spacious phagosomes
      (SP) and close-fitting phagosomes (CP). Three lines of evidence indicate that SP
      are the primary sites for intracellular CN survival and replication: (a) SP
      contained multiple, budding yeast cells, whereas CP contained only single yeast
      cells within a tightly bound phagosomal membrane; (b) the number of SP and the
      number of CN within SP increased considerably at 24 hours compared with at 2
      hours; and (c) microglial cultures challenged with heat- or amphotericin B
      treated CN had significantly fewer SP than those challenged with live CN. Both SP
      and CP phagosomes fused with lysosomes, suggesting that CN survival in SP was not
      due to failure of phagolysosomal fusion. In SP, there was attenuation and
      diffusion of capsular polysaccharide within the phagosome, whereas in CP the
      fungal capsules remained compact and homogeneous. Immunocytochemistry with an mAb
      directed to capsular glucoronoxylomannan supported continued synthesis of
      polysaccharide within SP. CONCLUSION: The results suggest that, in human
      microglia, CN survive and replicate within SP. Modification of CN capsular
      polysaccharide within SP may be a contributing factor to this aberrant microglial
      CN interaction.

PMID- 8558851
TI  - Oral inoculation of SCID mice with an attenuated herpes simplex virus-1 strain
      causes persistent enteric nervous system infection and gastric ulcers without
      direct mucosal infection.
AB  - BACKGROUND: After placement of herpes simplex virus type 1 (HSV-1) into the
      esophageal lumen of BALB/c mice, the virus replicated in enteric neurons within
      the esophagus and stomach and was transported to the sensory ganglia of the vagus
      nerve (nodose ganglia), where viral replication also occurs and where ultimately
      a long term latent infection is established. This described infection of
      immunocompetent mice primarily involved neuronal cells and associated satellite
      cells. EXPERIMENTAL DESIGN: Severe combined immunodeficient (SCID) mice were
      orally infected with an attenuated strain of HSV-1 to better identify sites of
      viral involvement in the gastrointestinal tract, particularly the mucosa.
      RESULTS: Three to five weeks after oral inoculation of SCID mice with HSV-1
      strain in1814, a persistent viral infection of the gastrointestinal tract was
      established in most of the mice. Extensive viral replication was detected by
      immunohistochemistry throughout pathways of the vagus nerve and within the
      intrinsic enteric nervous system. Despite this ultimately fatal infection, viral
      replication in the gut occurred almost exclusively in enteric neurons and their
      processes; viral proteins were occasionally seen in smooth muscle cells
      immediately adjacent to heavily infected enteric ganglia. More than 50% of these
      persistently infected mice, when killed 18 to 31 days postinoculation, had
      gastric ulcers that were identified grossly and histologically. Only one of the
      40 gastric ulcers was found to contain viral Ag. The remaining ulcers, although
      devoid of viral proteins, were found adjacent to virus-infected ganglia.
      CONCLUSIONS: HSV-1 can enter enteric neurons with minimal initial mucosal
      involvement, and once inside the nervous system, the virus is contained there
      despite the absence of a specific host immune response. Furthermore, chronically
      infected enteric neurons may provide an indirect mechanism for the pathogenesis
      of gastric ulcers in these immune-deficient mice.

PMID- 8558852
TI  - Abundant expression of translation initiation factor EIF-4E in post-meiotic germ
      cells of the rat testis.
AB  - BACKGROUND: Eukaryotic translation initiation factor EIF-4E is a key component in
      the regulation of translational efficiency of MRNAs and its increased expression
      may accelerate cell growth and division. EIF-4E has the potential to transform
      rat embryo fibroblast cells by cooperation with v-Myc or adenovirus E1A. Our
      previous study showed that a variety of tumor cells examined exhibited elevated
      levels of eIF-4E gene expression. Thus it is thought that overexpression of EIF
      4E can result in aberrant growth and cell transformation. EXPERIMENTAL DESIGN: To
      characterize rat EIF-4E, a clone containing rat eIF-4E cDNA was isolated from a
      rat testis cDNA library by screening with a synthetic probe prepared by the
      reverse transcription-polymerase chain reaction (RT-PCR) method. Based on the
      conserved nucleotide sequences between mouse and human eIF-4E cDNA, two
      oligonucleotide primers for RT-PCR were synthesized chemically. The cloned cDNA
      was sequenced and used as a probe for analysis of the expression level of eIF-4E
      mRNA in normal, differentiated rat tissues by Northern blot analysis. In situ
      hybridization analysis with digoxigenin-labeled antisense eIF-4E RNA as a probe
      was carried out to identify the eIF-4E-expressing sites in rat tissues. In
      addition, to analyse the phosphorylation level of EIF-4E, the proteins were
      fractionated from rat tissues by affinity column chromatography followed by
      isoelectric focusing (IEF)-gel electrophoresis. RESULTS: The nucleotide sequence
      of the eIF-4E cDNA is highly conserved in human, rat, and mouse. Extraordinarily
      elevated expression, more than 50-fold compared with that in the adult rat
      prostate, of eIF-4E was observed in testicular germ cells of rats of reproductive
      age, which was much greater than that in any tumor cell lines examined so far.
      The amount of EIF-4E fractionated from the adult rat testis was approximately 10
      times higher than that from the adult rat liver. At least half of the purified
      testicular EIF-4E proteins were phosphorylated, a ratio similar to that in other
      rat tissues such as liver. In situ hybridization analysis demonstrated that
      elevated expression of eIF-4E mRNA was mainly observed in post-meiotic germ
      cells. CONCLUSIONS: Full activity of EIF-4E in translation requires the
      phosphorylation of the protein on a specific serine residue. Thus the elevated
      level of EIF-4E observed in the adult rat testis should be reflected in increase
      of the functional activity of EIF-4E. Based on the results of in situ
      hybridization analysis and characterization of EIF-4E, it was concluded that
      abundant EIF-4E in the testis may play an important role in spermatogenesis
      through translational regulation of stage-specific mRNAs during germ cell
      development.

PMID- 8558853
TI  - Production of matrix metalloproteinases at the bone-implant interface in loose
      total hip replacements.
AB  - BACKGROUND: Incidence of aseptic loosening of hip prostheses is increasing in
      recent years. Previous studies suggested involvement of proteinases and cytokines
      in the accelerated bone lysis associated with loosening. EXPERIMENTAL DESIGN: To
      investigate the role of matrix metalloproteinases (MMPs) in the loosening we
      immunolocalized MMP-1 (tissue collagenase), MMP-2 (gelatinase A), MMP-3
      (stromelysin-1), MMP-9 (gelatinase B) and their common inhibitors, tissue
      inhibitors of metalloproteinases (TIMP-1 and TIMP-2), in the bone-prosthesis
      interface membranes. In situ hybridization was performed for the detection of MMP
      9 mRNA in the membranes. The amounts of these MMPs and TIMPs in the tissue were
      measured by the sandwich enzyme immunoassays and enzyme activities assayed using
      radiolabeled collagen, gelatin, and carboxymethylated transferrin substrates. We
      also examined the ability of the cells from interface membranes to resorb mouse
      calvaria bone. RESULTS: The membranes obtained from the loose bone-implant
      interface were composed of fibrous granulation tissue containing numerous
      multinucleated giant cells with high density polyethylene debris.
      Immunohistochemical examination revealed that the giant cells were strongly
      positive for MMP-9 and weakly for MMP-1. Expression of MMP-9 mRNA in the cells
      was demonstrated by in situ hybridization. MMP-2 and TIMP-2 were immunolocalized
      mainly in the fibroblasts. TIMP-1 was localized in the endothelial cells of the
      blood vessels and weakly in fibroblasts. However, MMP-3 was almost negative in
      the membrane tissue. Sandwich enzyme immunoassays showed that MMP-9 levels are
      significantly higher in both homogenates and culture media of the cup and stem
      interface membranes than the control pseudocapsule. Gelatinolytic activity was
      also remarkably higher in the membrane samples than the control. The cells
      isolated from the membranes had no ability to resorb calvaria bone. CONCLUSIONS:
      These data demonstrate that MMP-9 is produced by the multinucleated giant cells
      appeared by the reaction to polyethylene debris in the interface membranes. This
      proteinase may play a role in degradation of the extracellular matrix
      macromolecules present around and on the surface of the bone trabeculae,
      facilitating the osteoclastic bone resorption.

PMID- 8558854
TI  - High lipid levels in very low density lipoprotein and intermediate density
      lipoprotein may cause proteinuria and glomerulosclerosis in aging female
      analbuminemic rats.
AB  - BACKGROUND: Male rats are generally more prone to developing renal disease than
      female rats. However, female Nagase analbuminemic rats (NAR) are profoundly
      hyperlipidemic and develop proteinuria and glomerulosclerosis after
      uninephrectomy. Male NAR are less hyperlipidemic and are resistant to developing
      renal damage after uninephrectomy. Ovariectomy markedly decreases hepatic
      triglyceride secretion and plasma triglyceride levels in the female NAR.
      EXPERIMENTAL DESIGN: In this study, we investigated the relationship between
      plasma lipids and lipoprotein composition as well as the development of
      proteinuria, glomerular apolipoprotein and lipid deposition, and
      glomerulosclerosis in aging female and male analbuminemic rats. We also studied
      whether ovariectomy in female NAR at an early age would protect their renal
      function in old age. RESULTS: Aging hyperlipidemic female NAR with high
      triglyceride and cholesterol levels in very low density lipoprotein (VLDL) and
      intermediate density lipoprotein (IDL) were found to develop spontaneous
      proteinuria at 9 months of age. Glomerular lipid deposition and
      glomerulosclerosis were observed at 18 months of age. In male NAR that had lower
      lipid levels in VLDL and IDL, only mild proteinuria and no glomerular lipid
      deposition or glomerulosclerosis were observed up to the age of 22 months.
      Concurrently ovariectomized NAR demonstrated profound and persistent decreases in
      triglyceride and cholesterol content of VLDL and IDL as well as total plasma
      triglycerides, without much change in LDL, high density lipoprotein, total plasma
      cholesterol, or apolipoprotein B, and they remained completely free of
      proteinuria and glomerulosclerosis. Apolipoprotein B deposition in glomeruli was
      not different in the oldest female, male, or ovariectomized NAR. No important
      differences were observed in glomerular diameter between the three different
      groups up to the age of 1 year. CONCLUSIONS: These findings point to an important
      role of elevated lipid content of the triglyceride-rich lipoproteins VLDL and IDL
      in the pathogenesis of proteinuria and glomerulosclerosis in the female NAR.

PMID- 8558855
TI  - Heterogeneity and reproducibility of microvessel counts in breast cancer.
AB  - BACKGROUND: Microvessel counting has proven to be of prognostic value in breast
      cancer, as shown in different retrospective studies. However, methodology has not
      been studied widely, and this must be done before the method can become
      clinically applicable. The aim of this study was to determine the degree of
      heterogeneity and reproducibility of microvessel counts (MC) in breast cancer.
      EXPERIMENTAL DESIGN: In 10 cases of breast cancer, the available blocks (2-4
      blocks) containing invasive tumor parts were selected, and four sections (4
      microns) were cut with interdistances of 100 microns. In each section, two or
      three invasive areas (0.5 x 0.5 cm) were demarcated. Microvessels, visualized by
      immunohistochemistry (CD31 Ab), were counted by one observer in 10 systematically
      selected fields of vision (400 x magnification). Furthermore, microvessels were
      counted in four fields with the highest microvessel density ("hot spots").
      Coefficients of variation (CV) were calculated for the different sampling levels.
      RESULTS: Repeated MC yielded high intra- and interobserver reproducibility
      (correlation coefficients > 0.92). For the systematic counting method, CV between
      MC from different areas within one section was on average (17.1% (0.7-52.1). When
      comparing MC from corresponding areas in different sections from the same black,
      CV was on average 14.7% (0.5-41.9), and for MC from different blocks of the same
      tumor, CV was on average 25.8% (9.9-44.6). Nested ANOVA showed an approximately
      equal contribution to the total variance of the different sampling levels, except
      for the variation between sections (not significant). For the hot spot MC, CV for
      different sections from the same block was on average 11.1% (0.7-29.5) and for
      different blocks from the same tumor, 24.2% (5.7-54.9). Nested ANOVA showed that
      variation between different blocks from the same tumor contributed most to the
      total variance. CONCLUSIONS: There is a noteworthy heterogeneity in MC between
      different areas from the same section, between corresponding areas in different
      sections from the same block, and between different blocks from the same tumor.
      Consequently, one must carefully scan all the available tumor material in each
      case for the best hot spot. The hot spot approach is efficient and reproducible,
      but only a comparative prognostic evaluation can show whether it is clinically
      more useful than systematic counts.

PMID- 8558856
TI  - The School Health Policies and Programs Study (SHPPS): rationale for a nationwide
      status report on school health programs.

PMID- 8558857
TI  - Methodology.

PMID- 8558858
TI  - School health education.

PMID- 8558859
TI  - School physical education.

PMID- 8558860
TI  - School health services.

PMID- 8558861
TI  - School food service.

PMID- 8558862
TI  - School health policies prohibiting tobacco use, alcohol and other drug use, and
      violence.

PMID- 8558863
TI  - The School Health Policies and Programs Study (SHPPS): context, methods, general
      findings, and future efforts.

PMID- 8558864
TI  - Intrathoracic tracheal avulsion in three cats.
AB  - The surgical repair of complete intrathoracic tracheal avulsion in three cats is
      described. The initial presenting signs included dyspnoea, exercise intolerance
      and exertional cyanosis. Diagnosis was based upon the clinical signs, survey
      radiography and tracheal endoscopy. The ruptures were repaired via a right
      lateral thoracotomy made at the third or fourth intercostal interspace. Abnormal
      trachea was resected and a standard tracheal anastomosis was performed. Surgical
      results were considered excellent in all cases.

PMID- 8558865
TI  - What is your diagnosis?. Infected fracture with secondary osteomyelitis.

PMID- 8558867
TI  - Normal handling of diets--are all dogs created equal?
AB  - Observations on food tolerance in dogs have shown that differences occur between
      breeds--especially in the giant breeds which can have an increased frequency of
      soft stools. This may be explained, at least in part, by differences in the dogs'
      ability to utilise a diet. To investigate this phenomenon, four digestive trials
      were conducted using two canned and two dried commercial diets. The ability to
      digest most nutrients was lower in the great danes in three out of the four
      trials. The great danes also had a significantly higher faecal loss of water,
      sodium and potassium. The underlying causes should be associated with the
      relationship between body-weight and the gastrointestinal tract or with
      differences in transit time of the ingesta, particularly through the large
      intestine.

PMID- 8558866
TI  - Comparative study of marbofloxacin and amoxicillin-clavulanic acid in the
      treatment of urinary tract infections in dogs.
AB  - One hundred and four dogs with clinical signs of urinary tract infection were
      selected by 15 practitioners in a multicentric, controlled and randomised study.
      The clinical diagnosis was confirmed by urinalysis and imaging. Each dog received
      either marbofloxacin (2 mg/kg orally once daily or 4 mg/kg by subcutaneous
      injection every four days) or amoxicillin-clavulanic acid tablets (12.5 mg/kg
      twice daily) for 10 or 28 days, depending on the clinical diagnosis. Rectal
      temperature, general condition, appetite, urinary signs, defecation disorders and
      pain on abdominal palpation were monitored at each visit, the timetable depending
      on diagnosis: three urinalyses and at least three examinations per case were
      performed. Side effects were also thoroughly sought at each examination.
      Marbofloxacin and amoxicillin-clavulanic acid both yielded good bacteriological
      cure rates (96.2 per cent versus 85.0 per cent, respectively) and clinical cure
      rates (83.3 per cent versus 69.7 per cent). Fewer relapses were observed in those
      dogs that received marbofloxacin. Few mild side effects were recorded with both
      products.

PMID- 8558868
TI  - Comparison of hemilaminectomy and dorsal laminectomy for thoracolumbar
      intervertebral disc extrusion in dachshunds.
AB  - Neurological improvement after decompressive surgery, without routine therapeutic
      or prophylactic disc fenestration, was evaluated retrospectively in a consecutive
      series of 93 dachshunds with thoracolumbar disc extrusion. In 24 per cent of
      procedures, deep pain sensation was not elicited in at least one hind paw before
      surgery. Median neurological status one to seven days after surgery, at the time
      of discharge, was significantly improved after hemilaminectomy compared with
      dorsal laminectomy (P < 0.05). After hemilaminectomy, deep pain sensation was not
      elicited in one or both hind paws of 8 per cent of dogs in which pain sensation
      was elicited before surgery, compared with 21 per cent after dorsal laminectomy
      (P > 0.05). Improvement in neurological grade at follow-up examination two to 12
      weeks after hemilaminectomy was not significantly different compared with dorsal
      laminectomy (P > 0.05). Of dogs which were unable to walk before surgery, 83 per
      cent regained the ability to walk after hemilaminectomy, compared with 74 per
      cent after dorsal laminectomy (P > 0.05). In both groups, 50 per cent of dogs in
      which deep pain sensation was abnormal before surgery eventually regained the
      ability to walk after surgery (P = 1). One to two years after the first
      operation, a second laminectomy was performed in only 5 per cent of dogs because
      of extrusion of a different intervertebral disc which had not been fenestrated.

PMID- 8558869
TI  - Automobile-induced obstruction of the intrathoracic caudal vena cava in a dog.
AB  - A two-year-old labrador retriever was examined after a year's history of
      persistent ascites and exercise intolerance that began shortly after the dog was
      struck by an automobile. Contrast venography showed tortuosity of the
      intrathoracic caudal vena cava with partial obstruction caused by kinking of the
      vessel. Surgical resection of a fibrous connective band that was found to be
      tethering the intrathoracic vena cava ventrally, creating a partial obstruction,
      was performed. A hypothesis of the aetiology of this phenomenon is presented.

PMID- 8558870
TI  - The influence of speaking rate on vowel space and speech intelligibility for
      individuals with amyotrophic lateral sclerosis.
AB  - The relationship between speaking rate, vowel space area, and speech
      intelligibility was studied in a group of 9 subjects with amyotrophic lateral
      sclerosis (ALS) and 9 age- and gender-matched controls. Subjects read a standard
      passage (the Farm Passage) at three speaking rates, including HABITUAL, FAST, and
      SLOW. Vowel segment durations and target formant frequencies were measured at
      each speaking rate from select words containing the vowels /i/, /ae/, /a/, and
      /u/. To quantify changes in vowel space area across speaking rate, the area of
      the vowel quadrilateral was calculated for each speaker at each speaking rate. In
      addition, intelligibility estimates at each speaking rate were obtained for the
      dysarthric speakers. Results revealed that dysarthric speakers exhibited smaller
      vowel space areas and less systematic changes in vowel space as a function of
      speaking rate, when compared to the neurologically intact speakers. In an
      examination of the relationship between vowel space area and speech
      intelligibility, vowel space was found to account for 45% of the variance in
      speech intelligibility. This result suggests that vowel space area is an
      important component of global estimates of speech intelligibility.

PMID- 8558871
TI  - Temporal characteristics of speech in simultaneous communication.
AB  - The purpose of this investigation was twofold: (a) to determine if there are
      changes in specific temporal characteristics of speech that occur during
      simultaneous communication, and (b) to determine if known temporal rules of
      spoken English are disrupted during simultaneous communication. Ten speakers
      uttered sentences consisting of a carrier phrase and experimental CVC words under
      conditions of: (a) speech, (b) speech combined with signed English, and (c)
      speech combined with signed English for every word except the CVC word that was
      fingerspelled. The temporal features investigated included: (a) sentence
      duration, (b) experimental CVC word duration, (c) vowel duration in experimental
      CVC words, (d) pause duration before and after experimental CVC words, and (e)
      consonantal effects on vowel duration. Results indicated that for all durational
      measures, the speech/sign/fingerspelling condition was longest, followed by the
      speech/sign condition, with the speech condition being shortest: It was also
      found that for all three speaking conditions, vowels were longer in duration when
      preceding voiced consonants than vowels preceding their voiceless cognates, and
      that a low vowel was longer in duration than a high vowel. These findings
      indicate that speakers consistently reduced their rate of speech when using
      simultaneous communication, but did not violate these specific temporal rules of
      English important for consonant and vowel perception.

PMID- 8558872
TI  - Orofacial muscle activity of children who stutter: a preliminary study.
AB  - This study was a preliminary investigation of the relations between stuttering
      development and the maturation of speech motor processes. Electromyographic (EMG)
      activity was recorded from the orofacial muscles of children who stutter and
      their normally fluent peers during fluent and disfluent speech. Nine children who
      stutter (8 boys and 1 girl), ranging in age from 2:7 to 14:0, and 9 age- and sex
      matched children who do not stutter were subjects. Pairs of surface EMG
      electrodes were placed on children's faces overlying the anterior belly of the
      digastric (ABD), levator labii superior (ULIP), and orbicularis oris inferior
      (LLIP) muscles. Twenty segments of stuttered (for the children who stutter) and
      perceptually fluent speech were extracted from children's conversational speech
      samples. Spectra of the amplitude envelopes of the EMG activity were computed.
      The 3 oldest children who stutter showed evidence of tremorlike oscillations of
      EMG activity in the 5 to 15 Hz range during stuttering in either ULIP, LLIP, or
      ABD muscles. The younger children who stutter and the children who do not stutter
      demonstrated primary spectral peaks in the 1 to 4 Hz range during stuttered
      and/or perceptually fluent speech. It is hypothesized that the emergence of
      tremorlike instabilities in the speech motor processes of children who stutter
      may coincide with aspects of their general neural maturation and with the
      development of stuttering.

PMID- 8558873
TI  - Validity of parent report measures of vocabulary development for children with
      Down syndrome.
AB  - This study investigated the validity of a parent report measure of vocabulary
      development, the MacArthur Communicative Development Inventory: Words and
      Sentences (CDI), in children with and without developmental disabilities.
      Concurrent validity was examined by comparing results from the CDI and laboratory
      measures of vocabulary in 44 children with Down syndrome and 46 typically
      developing children with mental ages from 12 to 27 months. Significant
      correlations between .70 and .82 were obtained. Predictive validity was examined
      by measuring the vocabulary of 20 children with Down syndrome and 23 typically
      developing children first at approximately 20 months mental age and later at a
      mental age of approximately 28 months. Significant correlations were obtained
      between the CDI at Time A and all but one of the vocabulary measures at Time B (r
      = .46 to .66). These results establish the validity of parent measures of
      vocabulary development for children with Down syndrome and confirm their validity
      for typically developing children.

PMID- 8558874
TI  - Responsiveness of male adolescents with mental retardation to input from
      nondisabled peers: the summoning power of comments, questions, and directive
      prompts.
AB  - The expressive communication of individuals with cognitive impairments may be
      directly influenced by a partner's input, because such individuals often have
      limited conversational skills. Sequential analyses of dyadic interactions
      examined the effects of input by 32 normally developing adolescents on responses
      by male subjects with mental retardation whose communication modes included
      augmented communication. Results suggested that (a) verbal prompts in the form of
      questions were significantly more likely to receive responses from subjects with
      mental retardation than directive prompts, (b) comments were significantly more
      likely to receive responses from subjects with retardation than were directive
      prompts, when the nondisabled peer was male, and (c) male subjects with mental
      retardation were more likely to respond to input from male peers than from
      females. These data suggest that questions facilitate naturally occurring
      conversations but underscore the importance of evaluating gender-related effects
      on interaction involving persons with severe cognitive and communication
      impairments.

PMID- 8558875
TI  - Discourse topic management in senile dementia of the Alzheimer's type.
AB  - The purpose of the study was to provide a detailed evaluation of the topic
      management abilities of a group of subjects with senile dementia of the
      Alzheimer's type (SDAT) and to compare their patterns of topic management to that
      of a normal elderly (NE) subject group. Twenty-four subjects participated in the
      study: 12 SDAT subjects and 12 NE subjects matched along the variables of age,
      sex, and education. The evaluation of topic management was based on a 20-minute
      casual conversational interaction between the subject and a speech-language
      pathologist that was videotaped and later transcribed orthographically. Topic
      management was analyzed in terms of a modified version of the multidimensional
      topic coherence analysis developed by Mentis and Prutting (1991). The results
      indicated significant differences between the SDAT and NE subjects along a number
      of parameters of topic introduction and maintenance. The topic management
      profiles of the SDAT subjects were characterized by a reduced ability to change
      topics while preserving the discourse flow, difficulty in actively contributing
      to the propositional development of the topic, and a failure to consistently
      maintain topic in a clear and coherent manner. These problems appeared to be
      related to underlying problems across the discourse-pragmatic, linguistic, and
      cognitive domains; they highlight the need to more fully explore the interactions
      among deficits in SDAT and their effects on conversational discourse.

PMID- 8558876
TI  - Advanced verb form production in story retelling.
AB  - This study investigated the rate at which 60 elementary school children produced
      three advanced verb forms--past progressive, past perfect progressive, and past
      perfect--when asked to retell literate narratives, a discourse genre that
      originates from written prose and frequently contains these advanced verb forms.
      The three verb forms were embedded in nine story episodes and told to the
      children. The children were then asked to retell the stories. Verb form
      production by the children was scored as either "borrowed" or substituted
      spontaneous production. During their story-retelling episodes, the 6-, 7-, and 8
      year-old children borrowed all verb forms under investigation from the stimuli
      stories. They significantly preferred to borrow the past progressive over the
      past perfect progressive and past perfect forms. Rate of verb form production by
      8-year-old children was significantly higher than for the younger age groups.
      These data suggest that advanced verb form production is influenced by the
      children's sensitivity to the type of narrative register (i.e., 1st or 3rd person
      perspective), the propositional ability associated with narrative development,
      and the progressive meaning of the -ing suffix.

PMID- 8558877
TI  - Comparison of personalized cueing and provided cueing on the facilitation of
      verbal labeling by aphasic subjects.
AB  - This study investigated the effects of two associative learning tasks on aphasic
      subjects' labeling of novel symbols. It was designed to determine if aphasic
      subjects need to develop their own associations for word-symbols pairs
      (personalized cueing) to obtain the long-term labeling benefits observed in prior
      research or if comparable results are obtained when "ready-made" associations are
      used during training (provided cueing). The results showed that the two cueing
      techniques were equal in their ability to elicit correct responses from the
      subjects. The results also demonstrated the long-term effectiveness of both
      cueing procedures on the subjects' labeling accuracy up to 30 days after training
      was discontinued.

PMID- 8558878
TI  - Familial aggregation of phonological disorders: results from a 28-year follow-up.
AB  - This investigation is a follow-up to a longitudinal speech and educational
      outcome study involving approximately 400 normally developing children that was
      initiated in 1960. From this database, two groups of subjects (now aged 32-34),
      their spouses, and all of their offspring over the age of 3:0 (years:months)
      completed a battery of cognitive-linguistic and interview measures. One group
      (probands) consisted of 24 adults with a documented history of a moderate
      phonological-language disorder that persisted through at least the end of the
      first grade. The other group (controls) consisted of 28 adults who were known to
      have had normal articulation abilities as children. Results of this study
      demonstrated that, in comparison to the children of controls, the children of the
      proband subjects performed significantly more poorly on all tests of articulation
      and expressive language functioning and were significantly more likely to have
      received articulation treatment. There was, however, no evidence that specific
      misarticulations or phonological processes traveled within proband families.
      These results are in agreement with those of most previous family studies that
      have demonstrated an increased rate of occurrence of speech-language disorders of
      unknown origin in families including a first-degree relative who is similarly
      affected.

PMID- 8558879
TI  - Hierarchical planning abilities in children with specific language impairments.
AB  - The present study examined Cromer's (1983) claim that children with language
      impairments have a hierarchical planning deficit that affects language as well as
      performance on complex construction tasks. Subjects were 30 boys (ages 5-7
      years), 15 with specific language impairments (SLI) and 15 with normally
      developing language. Children were asked to build four hierarchical structures: a
      block construction, a puzzle construction, a simple straw construction, and a
      complex straw construction. Children who failed to complete the complex straw
      construction were taught how to construct the model using a sequential strategy.
      The two groups tended to perform comparably on the block and complex straw
      construction, the easiest and hardest of the four constructions. The two groups
      performed least comparably on the puzzle, simple straw construction, and the
      training task. On the basis of these findings and recent work by Greenfield
      (1991), we concluded that it is time to reject the notion that a central
      hierarchical planning mechanism underlies language and non-language structures
      that contain hierarchical components. The possible exception is early in
      development before language and manual actions become more autonomous and modular
      in nature.

PMID- 8558880
TI  - Conversational interactions of mothers and their preschool children who had been
      born preterm.
AB  - This study examined the conversational interactions of mothers and their 4.5-year
      old children, who had been born preterm, during a social problem-solving task
      asking each dyad to agree on the choice of a snack. Relative to comparison
      mothers, mothers of preterm children seemed to approach the task as a vocabulary
      lesson; they produced less complex sentences and were more likely to name the
      snacks and to test their children's knowledge of snack names. Comparison mothers
      were more likely to focus on the social negotiation aspect of the task, by
      offering more opinions and reasons. Discussed is whether the conversational
      strategies of mothers of preterm children reflect appropriate "fine-tuning" or a
      lag in adjusting to their children's emerging language skills because of a
      lingering "prematurity stereotype."

PMID- 8558881
TI  - Behavioral genetics: concepts for research and practice in language development
      and disorders.
AB  - This paper is an introduction to behavioral genetics for researchers and
      practitioners in language development and disorders. The specific aims are to
      illustrate some essential concepts and to show how behavioral genetic research
      can be applied to the language sciences. Past genetic research on language
      related traits has tended to focus on simple etiology (i.e., the heritability or
      familiality of language skills). The current state of the art, however, suggests
      that great promise lies in addressing more complex questions through behavioral
      genetic paradigms. In terms of future goals it is suggested that: (a) more
      behavioral genetic work of all types should be done--including replications and
      expansions of preliminary studies already in print; (b) work should focus on fine
      grained, theory-based phenotypes with research designs that can address complex
      questions in language development; and (c) work in this area should utilize a
      variety of samples and methods (e.g., twin and family samples, heritability and
      segregation analyses, linkage and association tests, etc.).

PMID- 8558882
TI  - Effects of age, education, and living environment on Boston Naming Test
      performance.
AB  - The 60-item Boston Naming Test (BNT; Kaplan, Goodglass, & Weintraub, 1983) was
      administered to 323 normal elderly subjects between the ages of 65 and 97. The
      combined effects of age, education, and living environment
      (institutionalized/independent living) on total test score was determined. These
      three variables accounted for 32% of the variance in BNT performance. Educational
      background accounted for the greatest proportion of the variance, followed by age
      and living environment. There was also a significant interaction between age,
      education, and living environment. Overall, increased age adversely affected BNT
      scores. However, institutionalized subjects with a sixth-ninth grade education
      performed poorly on the BNT regardless of age. In addition, there was little
      difference in BNT performance according to age or living environment for the well
      educated. (The only exceptions were the oldest institutionalized subjects, who
      performed poorly on the BNT regardless of level of education.) The data presented
      in this study should be helpful for those clinicians who administer the BNT to
      elderly patients who are institutionalized or who have a limited educational
      background.

PMID- 8558884
TI  - Reliability and sensitivity of paired comparisons and category rating in
      children.
AB  - Children's subjective judgments of speech clarity using the methods of paired
      comparisons and category rating were evaluated in this investigation. Eighty
      children with normal hearing between the ages of 4 and 8 years judged the clarity
      of sentences that were systematically bandpass-filtered using conditions that
      increased intelligibility as estimated by the Articulation Index. Subjects were
      classified into four age groups (4-, 5-, 6-, and 7-8-year age groups) with 20
      subjects per group. With use of materials and training methods suitable for
      children, judgments were obtained via the two psychophysical procedures (10
      subjects per age group for each procedure). Results indicated that children 5
      years of age and older were able to make reliable clarity judgments using either
      procedure; however, the method of paired comparisons was more sensitive than
      category rating in detecting differences between the bandpass-filtered
      conditions.

PMID- 8558883
TI  - Recognition of multiply degraded speech by young and elderly listeners.
AB  - This study investigated the hypothesis that age effects exert an increased
      influence on speech recognition performance as the number of acoustic
      degradations of the speech signal increases. Four groups participated: young
      listeners with normal hearing, elderly listeners with normal hearing, young
      listeners with hearing loss, and elderly listeners with hearing loss. Recognition
      was assessed for sentence materials degraded by noise, reverberation, or time
      compression, either in isolation or in binary combinations. Performance scores
      were converted to an equivalent signal-to-noise ratio index to facilitate direct
      comparison of the effects of different forms of stimulus degradation. Age effects
      were observed primarily in multiple degradation conditions featuring time
      compression of the stimuli. These results are discussed in terms of a postulated
      change in functional signal-to-noise ratio with increasing age.

PMID- 8558885
TI  - Evaluating hearing threshold differences between ears as a screen for acoustic
      neuroma.
AB  - Differences in pure tone thresholds between ears were evaluated at two different
      patient care facilities to determine this measure's value as a screen for
      acoustic neuroma. We evaluated the audiograms of tumor and nontumor groups to
      estimate the true positive rates and false positive rates for several decision
      rules. Threshold differences were found to be a more effective diagnostic tool
      for females than for males. However, even for the most effective rules, the
      efficiency of this test alone is mediocre, which indicates that hearing threshold
      differences between ears must be combined with other criteria for a cost
      effective approach to acoustic neuroma identification. Furthermore, tumor size
      was not predicted by the amount of threshold asymmetry between ears, which
      suggests that some large, potentially life-threatening tumors may be missed if
      pure tone threshold differences are the sole criterion for referral for
      additional tests.

PMID- 8558886
TI  - Effects of distance on vocal intensity.
AB  - The vocal response of speakers to change of distance from a listener is in
      dispute. Warren (1968) found that speakers obeyed the inverse square law when
      compensating for distance changes; that is, they decreased their vocal intensity
      by 6 dB when distance was halved. However, speakers in a study of Johnson, Pick,
      Siegel, Cicciarelli, and Garber (1981) changed their vocal intensity by much less
      than 6 dB. This study was an attempt to reconcile the conflicting results and to
      gain better understanding of what people know implicitly about the effects of
      distance on intensity. Speakers in the present study significantly changed their
      vocal intensity to compensate for changes in distance, but by a maximum of 2.46
      dB. Possible reasons for the different results are discussed.

PMID- 8558887
TI  - Disfluency clusters of children who stutter: relation of stutterings to self
      repairs.
AB  - The purpose of this study was to account for the frequency, type, and possible
      origins of speech disfluency clusters in the spontaneous speech of 3- to 6-year
      old children, 30 who stutter and 30 who do not stutter. On the basis of the
      Covert Repair Hypothesis (Postma & Kolk, 1993), which suggests that stutterings
      are the by-products of self-repairs or self-corrections of speech errors, three
      hypotheses were tested in attempts to account for the frequency and location of
      stutterings within speech disfluency clusters. Sequences of various types of
      speech disfluencies in utterances containing disfluency clusters were collected
      from audio/videotaped conversations between each of these 60 children and their
      mothers. Three types of speech disfluencies--overt self-repairs, covert self
      repairs, and within-word disfluencies ("stutterings")--and the disfluency
      clusters they comprised, were identified and analyzed frame-by-frame. Results
      indicated that children who stutter produced significantly more stuttering
      stuttering clusters (e.g., "I-I-I w-w-want ..." or "w-w-waaaant") and that,
      although children who do not stutter occasionally produced stutterings, they
      never produced stuttering-stuttering clusters. Furthermore, children who stutter
      produced significantly more stuttering-repair clusters, whereas children who do
      not stutter produced significantly more repair-repair clusters. Within the
      disfluency clusters of children who do not stutter, stutterings were more likely
      to follow an overt self-repair produced at a relatively fast speaking rate (6.6
      sylls/sec). Findings are taken to suggest that stuttering-stuttering clusters may
      help differentiate between children who do and do not stutter, and that speech
      errors, self-repairs, and speech disfluencies influence one another within and
      between adjacent sounds, syllables, and words in what appears to be a
      nonhappenstance and theoretically important fashion.

PMID- 8558888
TI  - Parents' speech and children's stuttering: a critique of the literature.
AB  - The role of parents in relation to their children's stuttering has been of great
      interest to speech-language pathologists for more than 50 years. As part of
      treatment, speech-language pathologists frequently advise parents to modify their
      speech behaviors when talking with their children. For example, parents are often
      told to speak more slowly and to refrain from interrupting or questioning the
      child excessively. Given the commonness of this advice, it is important to
      examine the research upon which it is based. This article contains a critical
      review of the literature concerning the role of parents' speech behaviors (e.g.,
      rate, interruptions, question-asking) in relation to their children's stuttering.
      Published studies are reported and analyzed in order to determine the extent to
      which parents may affect their children's stuttering through their own speech
      behaviors. The review indicates that there is little convincing evidence to
      support the view that parents of children who stutter differ from parents of
      children who do not stutter in the way they talk with their children. Similarly,
      there is little objective support for the argument that parents' speech behaviors
      contribute to children's stuttering or that modifying parents' speech behaviors
      facilitates children's fluency. Implications for treatment and for future
      research are discussed.

PMID- 8558889
TI  - Orolaryngeal reflex responses to changes in affective state.
AB  - Previous research has shown that the eye-blink startle reflex can be modulated by
      changes in affective state. The purpose of the present study was to determine
      whether human perioral and trigemino-laryngeal reflexes are sensitive to
      affective state changes. Impetus for this study comes from theories suggesting
      that orolaryngeal reflexes may be modulated by affective states, and as such
      influence voice and speech production. Subjects were 24 classically trained
      female sopranos (21-35 years). Each produced a pursing lip posture while
      sustaining the continuant /m/ at 440 Hz and at a comfortable voice intensity
      level. Simultaneously subjects were shown an aversive, pleasant, or neutral slide
      (experimental conditions) or no slide (control condition) and received
      unanticipated, servo-controlled mechanical taps to the midline upper lip.
      Perioral responses were recorded bilaterally from the orbicularis oris inferior
      (OOI) muscle using surface electromyography (EMG). Trigemino-laryngeal responses
      were obtained indirectly by measuring changes in the voltage analog of the voice
      fundamental frequency (VF0). Reflex responses were detected by smoothing and
      signal-averaging the VF0 and rectified EMG signals. Response magnitude and
      latency measures were compared across the affective valence and no-slide
      conditions. Statistically significant differences were not observed between
      conditions for the magnitude or temporal measures of either reflex. Significant
      differences, independent of affective valence, were observed between right and
      left early excitatory perioral response magnitudes. Differences between the
      startle and orolaryngeal reflexes, as well as the implications of these findings
      for speech motor control, are discussed.

PMID- 8558890
TI  - Short-term treatment careers and outcomes of previously untreated alcoholics.
AB  - OBJECTIVE: To describe treatment selection and outcomes over a 3-year follow-up
      period for 439 individuals who had drinking problems and had not yet received
      formal treatment at baseline. METHOD: By the 3-year follow-up, individuals had
      self-selected into one of four groups: no-treatment (n = 70), completed treatment
      (i.e., help was received only in Year 1 of follow-up: n = 109), additional
      treatment (i.e., help was received in Year 1, with more help in Years 2 and 3; n
      = 233), and delayed treatment (i.e., no help was received until Years 2 and 3 of
      follow-up; n = 27). RESULTS: Compared with individuals who remained untreated,
      individuals who sought help during Year 1 had more severe drinking problems,
      poorer psychosocial functioning and more negative life events at baseline;
      however, treated individuals had better drinking outcomes than untreated persons
      at the 1- and 3-year follow-ups. Compared to individuals who completed treatment
      in Year 1, additional treatment group members had more severe drinking problems
      at baseline and 1 year later, but better drinking outcomes at the 3-year follow
      up. Formal treatment in conjunction with Alcoholics Anonymous (AA) was associated
      with better drinking outcomes than formal treatment alone. In addition, more
      involvement with formal inpatient or outpatient treatment, or AA, was associated
      with more improvement on drinking indices. CONCLUSION: Overall, the findings
      suggest a reciprocal relationship between individuals' functioning and their
      participation in alcohol abuse interventions.

PMID- 8558891
TI  - Harmful effects of drinking and the use and perceived effectiveness of treatment.
AB  - OBJECTIVE: The objectives of the study were to examine relationships between: (1)
      harmful effects of drinking and use of treatment services, (2) the number of
      different types of harm experienced and whether or not treatment was obtained,
      and (3) the types of treatment obtained and the perceived effectiveness of
      treatment. METHOD: A secondary analysis was carried out of data obtained from the
      Canadian National Alcohol and Other Drugs Survey, conducted by Statistics Canada
      in 1989. The sample consisted of 1,954 respondents who reported experiencing at
      least one of six specified harmful effects from drinking. Chi-square tests were
      used to test relationships, with the alpha level set at 0.01. RESULTS: While
      21.5% of all current drinkers suffered at least one type of harm, only 10.6% of
      these obtained treatment (Objective 1). The number of harmful effects experienced
      is directly related to the likelihood of obtaining treatment: only 3.8% of those
      who had experienced one type of harm received treatment compared to 41.6% of
      those suffering all six types of harm (Objective 2). Almost three-quarters
      (73.8%) of those who received treatment obtained it through self-help groups such
      as Alcoholics Anonymous. While the findings about perceived effectiveness of
      treatment are tenuous because of the small numbers involved, more than half
      (52.0%) of those who had used self-help groups rated them as very effective, with
      most of the remainder (43.2%) rating them as moderately effective (Objective 3).
      CONCLUSIONS: The results confirm the contention that those who suffer harm from
      drinking are often difficult to involve in treatment. They also show, however,
      that the greater the number of harmful effects experienced, the more likely it is
      that a person will obtain treatment, suggesting that those most harmed are
      easiest to involve in treatment. The findings also emphasize that self-help
      groups are the overwhelmingly preferred mechanism for those who do obtain
      treatment, perhaps because of their greater accessibility and flexibility. Also,
      although the least reported harmful effect was on work, studies and employment,
      persons suffering this type of harm were the most likely to obtain treatment,
      suggesting that others affected by the harmed person may play a significant role
      in influencing him or her to obtain treatment.

PMID- 8558892
TI  - AA group dynamics and 12-step activity.
AB  - OBJECTIVE: AA groups may differ in perceived social dynamics but little is known
      about diversity in other potentially curative processes within AA. This study
      examined how three AA groups differed in perceived social dynamics, group
      emphasis on the 12 steps of AA, and completion of the 12 steps. METHOD:
      Questionnaires were completed by AA members affiliated with three mainstream AA
      groups. Surveys were done after investigators paid several visits to meetings as
      an aid to identifying group members. A majority of the AA members were male (64%)
      and had, on average, 45 months of continuous sobriety. RESULTS: Profile analyses
      showed that the three AA groups differed in perceived group cohesiveness,
      independence, aggressiveness and expressiveness. The AA groups also differed in
      how frequently members reported that the 12 steps were discussed in meetings.
      Step discussion was lowest in the group with highest aggressiveness. Differences
      were also found in the reported frequency of completing AA steps, such that
      members in the group with highest cohesiveness and step discussion reported
      having completed the fewest surrender (1-3) steps. CONCLUSIONS: AA groups appear
      to differ not only in perceived social environment (fellowship) characteristics,
      but in AA program implementation as reflected in discussion and completion of the
      12 steps. Such differences may be stable within groups across time. These
      findings further caution against regarding AA as a homogeneous entity. Clearer
      understanding of the heterogeneity among AA groups may provide bases for initial
      matching of individuals to AA experiences.

PMID- 8558893
TI  - Influence of alcoholism on the prognosis of schizophrenic patients.
AB  - OBJECTIVE: This study was undertaken to investigate possible differences in
      clinical, social and hospital prognosis in schizophrenics with or without
      codiagnosed alcoholism. METHOD: A representative sample was selected by a two
      stage random sample of sets from the total of 10,569 schizophrenic patients
      registered in the Croatian Psychotic Case Register in the period 1962-71. The
      resulting 449 schizophrenic patients were psychiatrically examined in 1973-75
      wherever they were found--at home, in a hospital or in a social-health
      institution. Of these original patients, 312 with or without a dual diagnosis of
      schizophrenia and alcoholism who were found at home were followed up until the
      final examination in 1990-91. RESULTS: Rate changes in 37 patients with the dual
      diagnosis were significant in the following characteristics: they were more often
      men, married, with a paranoid-hallucinatory disease form, were aggressive during
      examination, and were without psychiatric aftercare or regular
      psychopharmacotherapy (p < .01); they came from rural areas, had a mixed clinical
      picture with a deteriorating disease course and were less communicative and
      socially functional, and were without work self-initiative and personal income (p
      < .05). CONCLUSIONS: Schizophrenic patients found at home with codiagnosed
      alcoholism have poorer clinical, hospital, social and life prognosis and need
      longer hospitalization. They represent a special subgroup of schizophrenics
      requiring special therapeutic approach and early identification, inasmuch as
      their course of the disease has a tendency toward rapid deterioration. Prevention
      of alcoholism and its adequate treatment have far reaching implications for the
      prognosis of schizophrenic illness.

PMID- 8558894
TI  - The adverse impact of heavy episodic drinkers on other college students.
AB  - OBJECTIVE: College student survey data were examined to assess the impact of
      campus levels of heavy episodic drinking on nonheavy episodic drinking college
      students. METHOD: Analyses are based on a survey mailed to a random sample of
      college students at 140 American colleges. A total of 17,592 students (69%) at
      participating colleges responded. The study defined "heavy" drinking as the
      consumption of five or more drinks in a row for men and four or more for women,
      and divided schools into approximately equal categories: lower drinking level
      schools where 35% or fewer students were heavy drinkers; midlevel schools (36-50%
      heavy drinkers); and high drinking level schools where over 50% of the students
      were heavy drinkers. RESULTS: Residing on campus at high drinking level schools
      adversely affected students who were not engaging in heavy drinking. The odds of
      experiencing at least one problem from other students' drinking was 3.6 to 1 when
      nonheavy drinking students at high drinking level schools were compared to
      nonheavy drinking students at lower drinking level schools. Examples of such
      secondary heavy drinking effects included being hit or assaulted, having one's
      property damaged or experiencing an unwanted sexual advance. CONCLUSIONS: College
      alcohol prevention efforts should include a focus on the needs of students who
      are not engaging in heavy drinking yet may be adversely impacted by other
      students' heavy drinking.

PMID- 8558895
TI  - The relationship of alcohol sales to cirrhosis mortality.
AB  - OBJECTIVE: The goal of the current study was to evaluate the extent to which
      beverage specific alcohol sales (beer, wine and distilled spirits) are associated
      with cirrhosis mortality rates. METHOD: Cirrhosis mortality rates were related to
      measures of beverage specific alcohol sales data from 50 states in the United
      States taken over 12 years. Cirrhosis mortality rates were regressed over
      beverage specific alcohol sales in a time series cross-sectional analysis that
      included age compositions of state populations, measures of the availability of
      health care, population density, proscriptions on alcohol use, income, tourism
      and nighttime traffic fatality crash rates as covariates. RESULTS: Controlling
      for empirically observed first order autocorrelated errors in estimation, and the
      effects of other related covariates, the analyses showed that there was a
      beverage specific effect of distilled spirits sales on cirrhosis mortality rates.
      One percent increases in spirits sales were reflected in .282% increases in
      cirrhosis mortality rates. There were no significant effects for either beer or
      wine sales. CONCLUSIONS: The relationship of spirits sales to cirrhosis mortality
      rates may be explained most reasonably by the association of chronic heavy
      drinking with the consumption of spirits.

PMID- 8558896
TI  - Alcohol-related risk factors associated with HIV infection among patients
      entering alcoholism treatment: implications for prevention.
AB  - OBJECTIVE: Reports suggest that alcoholics may be at risk for HIV infection. In
      this article we examine several alcohol-related risk factors for HIV infection
      among patients entering alcoholism treatment in an AIDS epicenter. Our objective
      was to identify key factors for HIV prevention and screening among populations
      receiving treatment for alcohol abuse or alcohol dependence. METHOD: Clients (N =
      921) entering five alcoholism treatment centers in the San Francisco Bay area
      underwent an interview and blind serotesting for HIV antibodies (76% were male,
      16% men who had sex with men, 50% black, 10% Latinos and 6.5% were HIV
      seropositive). Logistic regression was used to predict HIV serostatus from five
      possible alcohol-associated risk factors, controlling for demographics and
      traditional HIV risk factors. These were alcohol impairment, attitudes about
      socializing in bars, increased sexual risk expectancies when drinking, enhanced
      sexual expectancies when drinking and decreased nervousness when drinking. Male
      and female heterosexuals and men with a history of homosexuality were analyzed
      separately. RESULTS: Among male and female heterosexuals, HIV infection was
      positively associated with higher alcohol impairment (OR = 2.69, p = .031) and
      negatively associated with higher sexual risk expectancies when drinking (OR =
      0.24, p = .075). Among men who had sex with men, HIV infection was positively
      associated with higher bar socializing orientations (OR = 10.06, p = .004).
      Infection was also negatively associated with higher alcohol impairment (OR =
      0.34, p = .052) and higher sexual risk expectancies when drinking (OR = 0.26, p =
      .024) for these men. CONCLUSIONS: Since these associations were independent of
      demographics and traditional HIV risk factors, our research suggests it may be
      important to also focus HIV screening and prevention on alcohol-related risk
      factors in AIDS epicenters. For heterosexual alcoholics, the focus should be on
      those with higher alcohol dependence. For male alcoholics who had sex with men,
      the focus should be on those who primarily socialize in bars. Further research is
      needed to determine why higher sexual risk perceptions when drinking were
      associated with lower rates of HIV infection for both groups, since this
      discovery may have important prevention implications. The negative association
      between infection and alcohol impairment among homosexual men also warrants
      further investigation.

PMID- 8558897
TI  - Assessing and tracking family histories of alcoholism.
AB  - OBJECTIVE: This study sought to (1) determine the rates of family history of
      alcoholism among a community sample, using both specific questions and structured
      interviews, (2) document conversions from negative (FH-) to positive (FH+)
      alcoholism diagnoses among parents and grandparents of subjects, and (3)
      investigate the concordance between interview and questionnaire methods in
      assessing alcoholism in family members. METHOD: Information concerning alcoholism
      among relatives of a sample of 1,201 (620 female) probands was gathered
      longitudinally over a 13-year period, spanning adolescence into adulthood. At
      Times 1 through 3 of the study, information was gleaned from personal interviews
      with subjects, medical health forms and information from subjects' parents, which
      was used to determine a "best estimate diagnosis." At Time 4, the Family History
      Research Diagnostic Criteria (FH-RDC) interview was used. RESULTS: The number of
      subjects having an alcoholic relative increased at each test time with the
      largest rise occurring at Time 4. Over 80% of subjects whose parent converted to
      FH+ at Time 4 had previously described that parent as a heavy or problem drinker.
      CONCLUSIONS: The higher than previously seen escalation in FH+ status occurring
      at Time 4 is speculated to be the result of one or more of the following: an
      actual increase in the number of relatives becoming alcoholic, a newfound
      awareness on the part of probands about alcohol-related problems, the fact that a
      global judgment or single behavior observation provides an inadequate indication
      of familial alcoholism, or that the FH-RDC may include a more global measure of
      "alcohol-related problems" or "problem drinking."

PMID- 8558898
TI  - The growth of conduct problem behaviors from middle childhood to early
      adolescence: sex differences and the suspected influence of early alcohol use.
AB  - OBJECTIVE: This study investigates the levels and rates of growth of conduct
      problem behaviors over time in an urban sample of American youth. Our hypotheses
      focused on differences between the sexes and between youths with and those
      without early use of alcohol without parental permission. METHOD: Data for this
      study are from an ongoing epidemiologic study of urban public school students,
      recruited originally at the time of their entry into Grades 1-2 between 1985 and
      1987. Each spring, from 1991 to 1993, a total of 1,212 students were interviewed
      privately for this study. A total of 408 (54.2% female, 84.7% black) respondents
      met study criteria as either an "early unsanctioned alcohol user" or an
      "abstainer." These youths constitute the analytic subsample. RESULTS: Estimates
      from longitudinal growth modeling analyses showed that boys and girls had
      different initial levels of conduct problem behaviors, but similar rates of
      growth. Both the initial level of conduct problem behaviors and the rates of
      growth were greater for early unsanctioned alcohol users as compared to
      abstainers. In a combined analysis the difference between early unsanctioned
      alcohol users and abstainers seemed to offset the initially observed sex
      difference. CONCLUSION: Early alcohol use without parental permission was
      associated with higher levels of conduct problem behaviors by the ages of 10-12
      years and higher rates of growth in those behaviors during the transition from
      late childhood to early adolescence for both boys and girls, although the levels
      differed by sex. It may be that unsanctioned early alcohol use puts youths on an
      accelerated pathway of conduct problem behaviors and development of conduct
      disorder in adolescence.

PMID- 8558899
TI  - Patterns of DSM-IV alcohol abuse and dependence symptoms in adolescent drinkers.
AB  - OBJECTIVE: Diagnostic criteria for alcohol use disorders have largely been
      developed from research and clinical experience with adults. This research was
      designed to describe patterns of DSM-IV alcohol use disorder symptoms, and other
      problem domains, in adolescents with alcohol problems. METHOD: A modified version
      of the Structured Clinical Interview for the DSM (SCID) was used to assess DSM-IV
      alcohol abuse and alcohol dependence symptoms in 91 male and 90 female adolescent
      drinkers with various levels of alcohol consumption and alcohol-related problems.
      The SCID was expanded to assess other alcohol problem domains thought to be
      relevant for adolescents. RESULTS: DSM-IV dependence symptoms showed moderate to
      high covariation, supporting the utility of the alcohol dependence construct in
      adolescence. Compared to previous reports from adult samples, some symptoms were
      relatively infrequent (e.g., withdrawal, medical problems). Tolerance had low
      specificity for the diagnosis of alcohol dependence. There was significant
      heterogeneity in the symptomatology of subjects with DSM-IV alcohol abuse.
      Although they are not in the DSM-IV criteria, alcohol-related blackouts, craving
      and risky sexual behavior were common in adolescents with DSM-IV alcohol
      dependence and abuse diagnoses. CONCLUSIONS: The data generally support the
      utility of DSM-IV criteria for alcohol dependence among adolescents. However,
      tolerance, withdrawal and medical problems appear to present differently in
      adolescents than has been reported in adults. Those with DSM-IV alcohol abuse
      diagnoses had very heterogeneous patterns of symptomatology, suggesting
      limitations of the criteria for DSM-IV alcohol abuse in adolescence. Alcohol
      related blackouts, craving and risky sexual behavior are common among adolescents
      with alcohol use disorders and are an important focus for assessment and
      treatment efforts.

PMID- 8558900
TI  - Intraclass correlation among measures related to alcohol use by young adults:
      estimates, correlates and applications in intervention studies.
AB  - OBJECTIVE: Alcohol intervention studies that allocate intact social groups to
      study conditions require adjustment to the usual analytic methods to account for
      the positive intraclass correlation that exists in such groups. This article
      presents intraclass correlations for measures related to alcohol use among young
      adults and discusses the use of those estimates to plan new studies. METHOD:
      Young adults aged 18-20 were selected at random from driver's license lists in
      each of the 15 communities participating in the Communities Mobilizing for Change
      on Alcohol project. Respondents were surveyed by telephone to assess their
      drinking habits and other factors related to alcohol use. Community-level
      intraclass correlations were computed for those measures, both prior to and after
      adjustment for person- and community-level covariates. RESULTS: The community
      level intraclass correlations tend to be small, with larger values for belief and
      attitude items than for self-reported behaviors. Even so, correlations of this
      magnitude can have important deleterious effects on the power to detect important
      treatment effects in an otherwise well-designed and well-executed study.
      Adjustment for person-level covariates often reduced those correlations, and
      adjustment for community-level covariates often reduced them substantially.
      CONCLUSIONS: There is measurable variation in measures related to alcohol use
      among young adults that is attributable to their community of residence. With
      adjustment for selected person- and community-level covariates, the magnitude of
      these correlations can be sharply reduced allowing the investigator to plan a
      more efficient community trial.

PMID- 8558901
TI  - Analysis of cut points for screening instruments for alcohol problems in the
      emergency room.
AB  - OBJECTIVE: The purpose of this study is to evaluate the performance of a number
      of alcohol screening instruments (CAGE, Brief MAST, AUDIT, TWEAK), in an
      emergency room population, against ICD-10 criteria for harmful drinking and for
      alcohol dependence from the CIDI, by gender, race and injury status. METHOD: A
      probability sample of patients were interviewed (N = 1,330) at the University of
      Mississippi Medical Center. Analyses were carried out on only current drinkers (n
      = 771; 58% of the sample). Instruments were compared on sensitivity, specificity
      and area under the curve using receiver operating characteristic (ROC) analysis
      to determine optimum cut points. RESULTS: Overall the TWEAK and AUDIT performed
      best (in relation to sensitivity and area under the ROC curve) at standard cut
      points (3 and 8, respectively) for both harmful drinking and alcohol dependence.
      These instruments did not perform equally well across all subgroups, however,
      particularly among women, and among whites where the CAGE, with a cut point of 1,
      outperformed both the TWEAK and AUDIT at standard cut points. The TWEAK at a cut
      point of 2 also did as well as the CAGE at a cut point of 1 among women.
      CONCLUSION: These data suggest that standard screening instruments do not perform
      equally well across ethnic and gender subgroups and that consideration of
      alternative cut points may be appropriate in some populations.

PMID- 8558902
TI  - A mechanochemical model for adult dermal wound contraction and the permanence of
      the contracted tissue displacement profile.
AB  - The healing of adult mammalian skin wounds involves a complex sequence of
      spatially and temporally coordinated processes. Wound contraction, by reducing
      the size of the injury, is an intrinsic component of full-thickness excisional
      dermal wound healing. The underlying biomechanics of wound contraction, however,
      are not fully understood, and little is known about the pathogenesis of severe
      medical conditions known as fibrocontractive diseases. The aim of this work is to
      investigate a deterministic mathematical model in order to obtain insight into
      the mechanistic relationships between wound contraction and associated normal and
      pathological healing processes. The model describes the essential roles of
      fibroblast and myofibroblast cells, a chemical growth factor and the
      extracellular matrix which includes type I collagen. The model results are
      qualitatively consistent with the biology of fibroplasia and wound contraction.
      It is shown that a contracted state evolves during a (long) transient phase of
      healing known as "proliferation", while collagen kinetics are fundamental to the
      considerably longer "remodelling" phase. Some quantitative results, notably on
      the evolution of wound contraction, compare favourably with experimental data.
      Application of the model to adult human dermal wound healing in vivo, with a
      greater understanding of the underlying biological mechanisms involved, may
      suggest strategies for controlling contraction and fibrocontractive diseases.

PMID- 8558903
TI  - Pathogen coexistence induced by density-dependent host mortality.
AB  - A model of two competing infectious diseases with complete cross-protection
      sharing one host allows for coexistence, provided that the host population is
      subject to strong density regulation. The phenomenon is caused by the different
      ways in which host density affects transmission rate and transmission period. The
      analysis suggest that disease coexistence is most likely when the two diseases
      differ significantly in virulence and transmission and that the evolutionary
      stability of the two-disease association depends critically on details in the
      functional relationship between virulence and transmission.

PMID- 8558904
TI  - The inhibition of maltose transport by the unliganded form of the maltose-binding
      protein of Escherichia coli: experimental findings and mathematical treatment.
AB  - Binding protein-dependent transport systems in Gram-negative enteric bacteria are
      multicomponent systems in which a soluble periplasmic binding protein of high
      substrate binding affinity establishes the major substrate recognition site.
      Usually, there are two integral membrane proteins which are thought to interact
      with the substrate loaded form of the binding protein to allow transport of
      substrate to occur. Transport is against the concentration gradient and needs
      energization by an ATP hydrolizing polypeptide. Overall transport is considered
      mainly unidirectional due to the high energy of ATP hydrolysis coupled to
      transport. In the study reported here, maltose transport in membrane vesicles in
      the presence of varying concentrations of unliganded maltose-binding protein but
      with constant amounts of maltose was measured. The conditions were chosen such
      that the concentration of maltose was always smaller than that of the binding
      protein and the initial concentration of the liganded binding protein was
      essentially constant. It was found that the initial rate of transport went
      through a maximum with increasing amounts of binding protein and declined
      thereafter. This finding strongly supports the conclusion that both the liganded
      and the unliganded forms of the binding protein interact with the membrane
      components of the transport system. The mathematical treatment of the
      experimental data allowed the ratio of the affinities for the membrane components
      of the substrate loaded and unloaded binding protein to be estimated. Published
      data on the binding protein-dependent transport of histidine in membrane vesicles
      of Salmonella typhimurium were also used. The data allowed the ratio of the
      binding affinity of the membrane components to the substrate-loaded and free
      binding protein to be determined. In addition, the KM of transport to the KD of
      binding protein was approximated.

PMID- 8558905
TI  - Lymphocyte development in irradiated thymuses: dynamics of colonization by
      progenitor cells and regeneration of resident cells.
AB  - Lymphocyte development in irradiated thymuses was analyzed using two
      complementary strategies: an in vitro experimental model and computer
      simulations. In the in vitro model, fetal thymus lobes were irradiated and the
      regeneration of cells that survived irradiation were examined, with the results
      compared to those of reconstitution of the thymus by donor bone marrow cells and
      their competition with the thymic resident cells. In vitro measurements of
      resident cell kinetics showed that cell proliferation is slowed down
      significantly after a relatively low (10 Gy) irradiation dose. Although the
      number of thymocytes that survived irradiation remained low for several days post
      irradiation, further colonization by donor cells was not possible, unless
      performed within 6 h after irradiation. These experimental results, coupled with
      the analysis by computer simulations, suggest that bone marrow cell engraftment
      in the irradiated thymus may be limited by the presence of radiation-surviving
      thymic resident cells and the reduced availability of seeding niches.

PMID- 8558906
TI  - Properties of evolutionarily stable learning rules.
AB  - Suppose a strategy for learning the optimal behavior in repeatedly played games
      is genetically determined. Then the animal is engaged in a learning game as well
      as the repeatedly played game. Harley (1981, J. theor. Biol. 89, 611-633)
      considers evolutionarily stable strategies in such learning games, called
      evolutionarily stable (ES) learning rules. Harley's work, though significant, is
      limited in that he does not establish the stochastic convergence of ES learning
      rules. Furthermore, his study of the relative payoff sum (RPS) approximation is
      limited to simulation experiments. Here, the stochastic convergence of ES
      learning rules and the RPS approximation is established. The ES learning rules
      and the RPS approximation were found to converge to the same quality, the so
      called matching ratio, with probability one.

PMID- 8558907
TI  - Pseudologica fantastica and other tall tales: the contagious literature of
      Munchausen syndrome.

PMID- 8558908
TI  - Imperial pathologies: medical discourse and drink in Dubliners' "Grace".

PMID- 8558909
TI  - To give suffering a language.

PMID- 8558910
TI  - Tenderness and steadiness: emotions in medical practice.

PMID- 8558911
TI  - Playing doctors: refiguring the doctor-patient relationship in Herve Guibert's
      AIDS novels.

PMID- 8558912
TI  - A new approach to analyzing the utility of immunophenotyping for predicting
      clinical outcome in acute leukemia. Eastern Cooperative Oncology Group.

PMID- 8558913
TI  - Cell surface c-kit receptors in human leukemia cell lines and pediatric leukemia:
      selective preservation of c-kit expression on megakaryoblastic cell lines during
      adaptation to in vitro culture.
AB  - We produced a monoclonal antibody MTK1 which recognized c-kit protein. Using
      MTK1, 31 leukemia cell lines and 76 leukemia blasts from pediatric patients were
      analyzed for expression of the c-kit receptor by flow cytometry. The c-kit
      receptor was detectable on four of four cell lines assigned to the
      megakaryo/erythromegakaryoblastic lineage and on one of seven cell lines of
      myeloid lineage. C-kit expression was not seen on any of 20 cell lines of
      erythroid and lymphoid lineages. Furthermore, c-kit was expressed on 16 of 24
      nonlymphoid blasts without platelet surface antigens (67%) and on six of eight
      non-lymphoid blasts with platelet surface antigens (75%), but was not detectable
      on 44 lymphoid blasts from pediatric leukemia patients. In these cases CD34 was
      expressed on 26 of 32 myeloid blasts (81%) and on 27 of 44 lymphoid blasts (61%).
      The findings indicate a dominant expression of the c-kit receptor on established
      cell lines assigned to the megakaryo/erythromegakaryoblastic lineage, though a
      high percentage of leukemic myeloblasts also expressed the c-kit receptor on
      their surface.

PMID- 8558914
TI  - The adhesion molecule E-cadherin and a surface antigen recognized by the antibody
      9C4 are selectively expressed on erythroid cells of defined maturational stages.
AB  - The antigen expression of immature erythroid bone marrow cells was studied using
      two recently generated monoclonal antibodies (mAb), mAb 67A4 and 9C4, with
      specificities for the epithelial cell adhesion molecule E-cadherin (E-cad; mAb
      67A4), and a novel 110 kDa differentiation antigen (mAb 9C4) with unknown
      molecular structure. Pappenheim staining of FACS-purified cells labeled with mAb
      9C4 and anti-glycophorin A (GA) revealed that the majority of the 9C4+GA- and
      9C4+GA+ cells consisted of erythroblasts. In contrast, the E-cad-positive
      population comprised normoblasts and erythroblasts. While the E-cad+GA- fraction
      contained mainly erythroblasts and basophilic normoblasts, the E-Cad+GA+
      population was enriched in orthochromatic and polychromatophilic normoblasts. By
      colony assays of affinity column-purified cells it could be shown that erythroid
      colony forming units (CFU-E) were enriched and erythroid burst forming units (BFU
      E) were depleted in the 9C4- and E-cad-positive fractions. Flow cytometric
      analysis of bone marrow cells double-labeled with mAb 67A4 and anti-CD71, anti
      CD117, anti-CD34, or anti-GA revealed that about 90% of the E-cad-positive cells
      coexpressed CD71, about 70% were positive for CD117, about 50% for GA, and only
      about 5% coexpressed CD34. The expression pattern of 9C4 antigen was similar to
      that of E-Cad with the exception that only a minority of the 9C4-positive cells
      coexpressed GA. Lymphoid and myeloid markers were negative on both the E-Cad- and
      9C4-positive populations. In these studies we describe the identification of a
      new mAb-defined antigen which is specifically expressed on erythroblasts and CFU
      E(9C4) and demonstrate that E-Cad is not only expressed on epithelial cells but
      also on erythropoietic cells of defined maturational stages.

PMID- 8558915
TI  - Interleukin 4 and interferon gamma costimulate the expansion of early human
      myeloid colony-forming cells. Proposal of a model for the regulation of
      myelopoiesis by interleukin 4 and interferon gamma and its integration with the
      regulation of the immune response.
AB  - We have previously shown that interleukin 4 (IL-4) and interferon gamma (INF
      gamma) reciprocally regulate the production of granulocytes and monocytes from
      mature monopotential hematopoietic progenitor cells, while at the level of the
      very primitive stem cells IFN-gamma is a selective inhibitor of proliferation and
      differentiation, and IL-4 has weak stimulatory effects. We investigated the
      effects of IL-4 and IFN-gamma on the expansion in suspension culture of myeloid
      colony-forming cells (CFCs) induced by either IL-3 or IL-1+IL-3, using on the one
      hand more differentiated CD34+HLA-DR strongly positive (HLA-DR++) and on the
      other hand more primitive Cd34+HLA-DR weakly positive (HLA-DR+/-) human bone
      marrow cells. It is shown that both IL-4 and IFN-gamma stimulate the IL-3- and IL
      3+IL-1-induced expansion of the number of CFCs in the HLA-DR+/- population. In
      the presence, but not in the absence of IL-1, additive effects of IL-4 and IFN
      gamma were seen. We could not demonstrate any IL-3-like effect by IL-4 on early
      human hematopoietic progenitors. No expansion of CFC number was seen in the HLA
      DR++ population. Based on these data and on data which we have published
      previously, a model for the regulation of myelopoiesis by IL-4 and IFN-gamma is
      proposed. In this model, IL-4 and IFN-gamma, which are both immune recognition
      induced inflammatory cytokines, both stimulate the expansion and recruitment of
      early myeloid progenitors, whereas at the level of their terminal
      differentiation, the balance between both cytokines determines whether
      preferentially monocytes/macrophages (IFN-gamma) or granulocytes (IL-4) are being
      produced. At the level of the most primitive cells, the inhibitory action of IFN
      gamma might prevent differentiative exhaustion of the stem cell compartment in
      situations of hematopoietic stress.

PMID- 8558916
TI  - The beta subunit common to the GM-CSF, IL-3 and IL-5 receptors is highly
      polymorphic but pathogenic point mutations in patients with acute myeloid
      leukaemia (AML) are rare.
AB  - The intracytoplasmic tail of the granulocyte-macrophage colony-stimulating factor
      receptor (GM-CSFR) beta c chain is essential for the activation of ligand
      mediated signal transduction pathways in myeloid cells. Alterations in this
      region could deregulate normal signalling processes. We have therefore used RT
      PCR-SSCP analysis of the receptor tail to look for point mutations in RNA from 35
      patients with acute myeloid leukaemia (AML) and 10 haematologically normal
      controls. Patterns differing from those of the haemopoietic cell line TF-1 were
      detected in 25/35 (71%) AML patients and 8/10 (80%) normal controls. A total of
      six base substitutions were identified by sequencing. Three were conservative for
      the amino acid involved, three led to amino acid differences, valine652-
      >methionine, glycine647-->valine and proline603-->threonine. One alteration was
      found only in a normal control, the other five were all found in both AML
      patients and normal controls suggesting that they were DNA polymorphisms. Two
      substitutions were particularly common with allele frequencies of 0.23 (G1972-
      >A, unchanged proline648) and 0.13 (C1306-->T, unchanged serine426). These
      results indicate that the GM-CSFR beta c chain is highly polymorphic but point
      mutations of the intracytoplasmic tail do not appear to contribute frequently to
      the pathogenesis of AML.

PMID- 8558917
TI  - Chemotherapy versus transplants for acute myelogenous leukemia in second
      remission.
AB  - The best therapy for persons with acute myelogenous leukemia (AML) in 2nd
      remission is unknown. Bone marrow transplants from an HLA-identical sibling are
      reported to be better than chemotherapy but this is controversial. The objective
      of the study was to compare 3-year leukemia-free survival (LFS) in comparable
      subjects receiving chemotherapy or a transplant. 485 persons with AML in 2nd
      remission were studied. The chemotherapy cohort included 244 persons treated on
      trials of the British Medical Research Council, Eastern Cooperative Oncology
      Group and MD Anderson Hospital. The transplant cohort included 257 persons
      transplanted worldwide and reported to the international Bone Marrow Transplant
      Registry (16 were also chemotherapy subjects.) Subjects were selected for
      comparable age and year of treatment. Preliminary analyses identified two factors
      correlated with LFS: age < or = or > 30 years and 1st remission duration < or =
      or > 1 year; subsequent analyses were partitioned accordingly. Three-year
      probabilities of treatment-related mortality with chemotherapy and transplants
      were 7% (95% confidence interval, 3-15%) vs 56% (49-63%). Three-year leukemia
      relapse probabilities were 81% (74-86%) vs 41% (33-49%). Three-year probabilities
      of LFS were 17% (12-23%) vs 26 (20-32%). Cohort analysis showed significantly
      higher LFS with transplants vs chemotherapy in persons < or = 30 years and 1st
      remissions > 1 year (41% (29-53%) vs 17% (7-32%); P = 0.017) and those in > 30
      years with 1st remissions < or = 1 year (18% (9-29%) vs 7% (2-16%); P = 0.046).
      Others had comparable LFS with both treatments. These data indicate better LFS
      with HLA-identical sibling transplants than chemotherapy in some persons with AML
      in 2nd remission.

PMID- 8558918
TI  - Establishment of a human B-CLL xenograft model: utility as a preclinical
      therapeutic model.
AB  - Chronic lymphocytic leukemia (CLL), a proliferative disease of mature looking B
      lymphocytes, is the commonest leukemia in western countries. It remains incurable
      by available treatment modalities. We report on the establishment of a permanent,
      EBV-negative, B-CLL line (WSU-CLL) from the peripheral blood of a patient with
      CLL. The cells grow as suspension in liquid culture, express IgG lambda and other
      B cell markers and show lg heavy and light gene rearrangements. Karyotypic
      analysis shows 45,X,del(3)(p14;p24),t(4;12;12) (q31;q22;p13), t(5;12) (q31;p13),
      add(16)(q24)X2, t(18;21) (q12;p12). WSU-CLL forms colonies when grown on soft
      agar. A xenograft model was established by injecting the WSU-CLL cells
      subcutaneously (s.c.) in severe combined immune deficient (SCID) mice. When the
      s.c. tumor was transplanted in vivo to other SCID mice, the success rate was 100%
      with a doubling time of 7.3 days. The CLL-SCID xenograft model was used to test
      the efficacy of selected standard chemotherapy drugs and new therapeutic agents
      against WSU-CLL. The cell line and the xenograft described can be used as a model
      to facilitate the development of new therapeutic agents against CLL in man.

PMID- 8558919
TI  - Circulating malignant lymphocytes from Sezary syndrome express high level of
      glycoproteins carrying beta (1-6)N-acetylglucosamine-branched N-linked
      oligosaccharides.
AB  - The circulating forms of malignant cells from patients with Sezary syndrome
      exhibit on their glycoproteins a high level of beta (1-6)GlcNAc-branched N-linked
      oligosaccharides, a particular species of glycans related to the metastatic
      potential of several tumors and T lymphocytes activation. An increased activity
      of the N-acetylglucosaminyltransferase V and of the beta (1
      4)galactosyltransferase, two enzymes implicated in beta (1-6)GlcNAc-branching is
      also found. Nevertheless, contrary to activated normal T lymphocytes, Sezary
      lymphocytes in agreement with their non-proliferating state, do not exhibit
      increased thymidine uptake. This result suggests that expression of the beta (1
      6)GlcNAc-branched N-linked carbohydrates could be related to some of the
      malignant properties of Sezary lymphocytes.

PMID- 8558920
TI  - The (2;5)(p23;q35) translocation in cell lines derived from malignant lymphomas:
      absence of t(2;5) in Hodgkin-analogous cell lines.
AB  - The CD30+ anaplastic large cell lymphoma (ALCL) represents a new lymphoma entity
      thought to be related to Hodgkin'S disease (HD), but displaying also its own
      unique features. Cytogenetic studies of ALCL have demonstrated the presence of a
      (2;5)(p23;q35) translocation in a substantial number of these cases. Recently,
      the t(2;5) has been cloned and described to represent fusion of the NPM gene with
      the ALK gene on chromosome 5. To better define the spectrum of lymphomas
      containing this abnormality we have analyzed 50 continuous human cell lines
      established from various types of non-Hodgkin's lymphoma, ALCL and HD. In a first
      step, the expression of the NPM-ALK fusion gene was examined by reverse
      transcriptase-polymerase chain reaction (RT-PCR). In a second step, the t(2;5)
      carrying cells were tested for the translation of functional chimeric mRNA into a
      fusion protein by immuno-staining of single cells with a polyclonal antibody. The
      NPM-ALK fusion transcript and the p80 protein were detected in eight of nine ALCL
      cell lines. We were unable to find PCR evidence for the t(2;5) in any of the non
      ALCL cell lines including other CD30+ cell lines. As all seven bona fide HD cell
      lines were NPM-ALK-negative, these results do not support the notion that the
      t(2;5) represents a chromosomal aberration common to both ALCL and HD.

PMID- 8558921
TI  - Preservation of functional and regulatory domains of expressed bcl-2 genes in non
      Hodgkin's lymphoma.
AB  - The most common translocation in human lymphoma, t(14;18)(q32;q21), recombines
      the bcl-2 gene with the immunoglobulin (Ig) heavy-chain locus leading to the
      production of high levels of chimeric RNAs and the resulting 26 kDa bcl-2
      protein. The oncogenic role of the bcl-2 gene has been shown by the suppression
      of a variety of programmed cell deaths (apoptosis). Bcl-2 is able to interact
      with other members of the bcl-2 family through at least one of its conserved
      dimerization domains. Although overproduction of the wild-type protein appears
      sufficient for conferring a selective growth or a survival advantage to
      hematopoietic cells, the mode of activation of the proto-oncogene remains to be
      elucidated. In a first step, we examined and quantitated the expression of the
      bcl-2 gene in primary biopsies of non-Hodgkin's lymphomas (NHL) as well as in
      cell lines derived from NHLs. The results show that bcl-2 expression is found in
      a variety of hematopoietic lineages, but is most strongly associated with the B
      cell lineage. Within the B cell lineage, the expression levels vary depending on
      the differentiation as well as on the t(14;18) rearranged status. The
      quantitative measurements show high steady-state mRNA levels in early and in
      t(14;18) arranged B cells, whereas bcl-2 expression decreases with further B cell
      maturation and differentiation. In a second step we analyzed the bcl-2 mRNA for
      secondary genetic alterations, which may alter regulatory regions rendering it
      more tumorigenic. For this purpose, we chose a combined RT-PCR/SSCP method in
      order to screen out mutations of alleles which are not expressed. Different
      migration patterns of SSCP products were found only in two cell lines and
      subsequent sequencing revealed that the functional domains are not affected. Our
      data suggest that the dimerization properties of this protein are preserved in
      tumor cells and that modifications of the bcl-2 gene by the somatic hypermutation
      mechanism are not involved and do not influence the pathobiology of NHL.

PMID- 8558922
TI  - A case of malignant mastocytosis with circulating mast cell precursors: biologic
      and phenotypic characterization of the malignant clone.
AB  - The phenotypic and biologic properties of malignant cells in a case of aggressive
      mastocytosis with multi-organ involvement, circulating mast cell precursors and
      absence of skin infiltrates were analyzed. Circulating mast cell precursors were
      detected by immunostaining using antibodies against mast cell tryptase as well as
      by electron microscopy. These progenitors were tryptase+/chymase- (MCT) and
      accounted for 10 to 20% of nucleated mononuclear blood cells (MNC). A subset of
      them contained metachromatic granules. As assessed by combined toluidine
      blue/immunofluorescence staining, the granulated mast cell precursors were found
      to express CD9 (P24), CD33 (gp67) and CD44 (Pgp-1), but not basophil-related
      markers (CD11b (C3biR), CDw17 (lactosylceramide), CD123 (il-3R alpha))or monocyte
      related antigens (CD14, CD15). Expression of the mast cell growth factor (MGF)
      receptor, c-kit(CD117), was also demonstrable, whereas the skin mast cell marker
      C5aR (CD88) could not be detected on mast cell precursors. The ligand of c-kit,
      recombinant human (rh) stem cell factor (SCF = MGF), induced histamine release
      from circulating mast cell progenitors, whereas rhC5a, a potent skin mast cell
      /basophil-agonist, was ineffective over the dose-range (10(-9) to 10(-7(M))
      tested. Analysis of mast cell antigens in malignant mastocytosis or mast cell
      leukemias may be helpful to establish a diagnosis and to determine the phenotype
      of the clone.

PMID- 8558923
TI  - Deletion of the short arm of chromosome 12 is a secondary event in acute
      lymphoblastic leukemia with t(12;21).
AB  - Translocation t(12;21) has been described as a nonrandom event in acute
      lymphoblastic leukemia (ALL) in patients with deletion of the short arm of
      chromosome 12, using fluorescence in situ hybridization techniques. Extensive
      FISH experiments were performed in order to re-examine the short arm of
      chromosome 12 in three children with ALL, previously shown to have t(12;21). It
      was shown that the t(12;21) is undetectable by routine R-banding technique and
      that the translocated 12 looks like a cytogenetically normal chromosome 12 in the
      three patients. Partial 12p deletion involving the TEL locus was shown to be
      interstitial in one patient with 12p- by using cosmid and YAC probes. In the
      second patient, the 12p- chromosome was secondary to the translocation since it
      was observed in about one half of the metaphases analyzed with FISH. In the third
      patient, the region of TEL usually rearranged in the t(12;21) displayed a
      germline pattern by Southern blotting, at diagnosis and in relapse. A few
      metaphases showed associated 12p- by standard cytogenetics, only in relapse. Thus
      we conclude that the TEL allele not involved in t(12;21) is inconstantly lost in
      patients with this subtype of ALL and occurs on the 12p- chromosome. These data
      question the status of tumor suppressor gene hypothesized for TEL.

PMID- 8558924
TI  - Differential efficacy of adenoviral mediated gene transfer into cells from
      hematological cell lines and fresh hematological malignancies.
AB  - As a first step to evaluate the possibility of gene therapy using adenoviral
      vectors in hematological malignancies in vivo, we tested the efficacy of gene
      transfer by a recombinant adenovirus in cell lines and fresh cells from various
      hematological neoplasms. Thirteen cell lines and samples from 27 patients were
      studied. Cells were infected by a recombinant adenovirus expressing beta
      galactosidase gene (Ad RSV betagal) and efficacy of transduction assessed by
      evaluating betagal expression in cells with a histochemical method. After
      infection of the cells at a multiplicity of infection (MOI) of 200 p.f.u./cell,
      the percentage of beta gal-positive cells after 48h was high in two cell lines.
      K562 (64%) and RPMI 8226 (a myeloma cell line, 65%), relatively large in the two
      myeloma cell lines tested (41% and 20%, respectively) and in MT4 (an adult T cell
      leukemia cell line, 38%) and low or absent in other cell lines. In fresh samples
      from AML, ALL, CLL, NHL, myeloma and MDS, no betagal positive cells were seen 48h
      and 72h after infection, except in one case of myeloma and one case of CLL (where
      10% and 2% of betagal positive cells were seen after infection, respectively).
      Exposure of fresh malignant cells to GM-CSF before and during adenoviral
      infection, in three cases, did not increase the number of transfected cells. This
      suggests that adenoviral vectors, at least in their present form, cannot
      efficiently be used for direct gene transfer in hematological malignant cells.

PMID- 8558925
TI  - Are growth factors leukemogenic?
AB  - The National Cancer Institute (NCI) recently alerted clinicians to the
      possibility that patients, entered on a NCI-sponsored cooperative group trial of
      doxorubicin and cyclophosphamide adjuvant therapy for breast cancer, may be at
      high risk of developing secondary acute myeloid leukemia (AML). Secondary AML
      following standard doses of doxorubicin and cyclophosphamide is uncommon,
      suggesting that the high risk on this trial may result from its higher-than
      standard doses of chemotherapy. However, the cases of secondary AML were
      characteristic of the type that follows treatment with topoisomerase II-active
      agents, especially etoposide, and this type of secondary AML is rare after
      treatment with either cyclophosphamide or doxorubicin at any dose. We raise the
      possibility that another component of this trial, hematopoietic growth factors to
      decrease the toxicities related to myelosuppression, may play an important role
      in the development of secondary AML. Growth factors not only stimulate
      hematopoietic progenitor proliferation and differentiation, they also regulate
      hematopoietic cell survival by interfering with apoptosis (programmed cell
      death). Inhibition of apoptosis by a variety of genetic factors is an important
      mechanism of oncogenesis, and appears to be the initiating event in some
      malignancies. Growth factor-mediated suppression of the apoptotic death of
      hematopoietic progenitors damaged by chemotherapy may contribute to their
      leukemic transformation.

PMID- 8558926
TI  - Acute promyelocytic leukemia after treatment of malignant glioma in a patient
      with von Recklinghausen's disease: case report and review of the literature.

PMID- 8558927
TI  - Dicentric (9;12) in pre-B acute lymphoblastic leukemia (ALL) in an infant.

PMID- 8558928
TI  - Frequency of molecular elimination of Ph1 clone in chronic myelogenous leukemia
      (CML) with interferon alpha.

PMID- 8558929
TI  - Persistence of AML1/ETO fusion mRNA in t(8;21) acute myeloid leukemia (AML) in
      prolonged remission: is there a consensus?

PMID- 8558930
TI  - Quinine-induced voltage activated inward current in the megakaryocytes of an ALL
      patient.

PMID- 8558931
TI  - CD34 antigen expression in adult acute lymphoblastic leukemia.

PMID- 8558932
TI  - Refractory cytopenia with multilineage dysplasia: further characterization of an
      'unclassifiable' myelodysplastic syndrome.
AB  - Myelodysplastic syndromes (MDS) characterized by multilineage cytopenias and
      dysplasia but lacking an increase in blasts, with no Auer rods or monocytosis, do
      not exactly fit any of the categories of the French-American-British (FAB)
      classification of MDS and are often diagnosed as refractory anemia (RA),
      refractory anemia with ringed sideroblasts (RARS), or 'unclassifiable' MDS. It
      has been suggested that these 'unclassifiable' cases form a distinct subset with
      a clinical behavior more like that of refractory anemia with excess of blasts
      (RAEB) than that of RA or RARS, but few studies have been undertaken that
      characterize this group. We compared the clinical, hematologic, morphologic and
      cytogenetic features of 18 such patients - for whose disease we propose the
      designation 'refractory cytopenia with multilineage dysplasia' (RCMD) - to those
      of 42 patients meeting the FAB criteria for RA or RARS (14 patients) and RAEB (28
      patients). Our results show that cytopenias in RCMD are more severe than those in
      RA or RARS, but are similar to those in RAEB. Erythroid hyperplasia and
      dyserythropoiesis are the main findings in bone marrow specimens of RA or RARS,
      but the major features in RCMD are multilineage proliferation and dysplasia,
      which, except for the lack of increased blasts resemble the findings in RAEB.
      Only 1/14 patients (7%) with RA or RARS had an abnormal karyotype, whereas RCMD
      resembled RAEB in terms of the frequency (41 vs 50%, respectively) and type of
      karyotypic lesions. Abnormalities of chromosomes 5 and 7 (excluding del(5q) as an
      isolated finding) or complex aberrations were seen only in RCMD and RAEB. in
      RCMD, the median survival was 24 months, with a 4-year survival rate of48 +/-
      13%, intermediate between the findings in RA/RARS (107 months and 77 +/- 12%,
      respectively) and RAEB (18 months and 27 +/- 9%, respectively). Our data indicate
      that RCMD is a distinct subset of MDS, with an unfavorable clinical outcome. The
      designation 'refractory cytopenia with multilineage dysplasia' emphasizes the
      differences between such cases and the primarily dyserythropoietic, indolent
      subgroups of MDS, such as RA or RARS.

PMID- 8558933
TI  - Secondary acute promyelocytic leukemia. Characteristics and prognosis of 14
      patients from a single institution.
AB  - The aims of this study were to analyze the characteristics and outcome of
      patients with secondary acute promyelocytic leukemia (APL) and compare them to
      those with primary APL. One hundred and thirteen patients referred to our service
      with a diagnosis of APL were reviewed. Fourteen were classified as secondary APL.
      Nine were induced with chemotherapy, and five with all-trans retinoic acid plus
      chemotherapy. Pretreatment characteristics, response to therapy and outcome of
      primary vs secondary APL were compared by standard statistical methods. Secondary
      APL constituted 12% of all APL cases. Patients with secondary APL were
      significantly older (median age 56 vs 36 years; P < 0.01) and had a lower
      incidence of hypofibrinogenemia (P < 0.01) than those with primary APL. The
      complete response (CR) rates were similar with secondary vs primary APL (CR rates
      79 vs 69%), as were CR duration and survival. The CR rates at 5 years were 57 and
      45%, respectively(P not significant), and the survival rates 37 and 35%,
      respectively (P not significant). The incidence of secondary APL within APL
      disease (12%) was similar to the incidence of secondary acute myeloid leukemia
      (AML) in karyotypes not known to be therapy-related (diploid, t(8;21), inversion
      16: incidences 9 to 12%), but was significantly lower than in karyotypes known to
      be therapy-related (chromosome 5 or 7 abnormalities, 11q; incidences 30 and 33%).
      We conclude that secondary APL has general characteristics and outcome similar to
      primary APL. it is more likely a second primary rather than therapy-related AML,
      and should be treated in a manner similar to primary APL.

PMID- 8558934
TI  - Granulocyte colony-stimulating factor following chemotherapy in elderly patients
      with newly diagnosed acute myelogenous leukemia.
AB  - Given the high treatment-related mortality in elderly patients with acute
      myelogenous leukemia (AML), we undertook a study using granulocyte colony
      stimulating factor (G-CSF) following chemotherapy in an effort to ameliorate
      toxicity. Patients ( > 60 years) received induction with idarubicin 12 mg/m2/day
      x 3 and cytosine arabinoside (Ara-C) 200 mg/m2/day x 5. A second course of
      chemotherapy consisting of mitoxantrone 12mg/m2/day x 3, etoposide (VP-16) 150
      mg/m2/day x 3 and Ara-C 200 mg/m2/day x 4 was given approximately 1 month after
      achieving a complete remission (CR) or immediately if patients failed the first
      induction. Twenty-four hours following completion of the chemotherapy, G-CSF (10
      micrograms/kg/day continuous i.v. infusion) was started. A historical control
      group of 28 patients treated without G-CSF was used for comparison. Twenty-six
      patients were evaluable for response. Following induction, the recovery of
      neutrophils to greater than 500/microliters and 1000/microliters was more raped
      in the responders who received G-CSF compared to historical controls (median 13
      vs 17 days, P = 0.008; 14 vs 19 days, P = 0.005). The toxic death rate of 8% in
      the study group was significantly lower than the 32% mortality observed in the
      historical controls (P = 0.04). There was no difference in supportive care
      requirements or infectious complications. The complete remission (CR) rate was
      58% in the entire study group with 71% of de novo AML patients achieving CR.
      Disease-free survival and overall survival were comparable between the study and
      historical control groups. These results indicate that G-CSF benefits elderly
      patients after intensive chemotherapy for AML by decreasing the duration of
      neutropenia. The reduced neutropenic period may have contributed to the small
      number of early toxic deaths.

PMID- 8558935
TI  - Homoharringtonine in patients with myelodysplastic syndrome (MDS) and MDS
      evolving to acute myeloid leukemia.
AB  - Current anti-leukemic chemotherapy in patients with myelodysplastic syndromes
      (MDS) and MDS evolving to acute myeloid leukemia (AML) is associated with low
      response rates and high treatment-related toxicity. Homoharringtonine (HHT) is a
      novel cephalotaxime alkaloid with reported efficacy in relapsed and de novo AML
      and more recently, chronic myeloid leukemia. Although its mechanism(s) of action
      is not completely understood, in vitro studies have demonstrated both cytotoxic
      and differentiating activity in leukemic cells, as well as intra-cellular changes
      suggestive of apoptotic cell death. In a phase II trial, HHT was administered at
      a dose od 5 mg/m2 by 24-h continuous infusion daily for 9 days to patients with
      MDS and MDS evolving to AML (MDS/AML). Twenty-eight patients (MDS 16, MDS/AML 12)
      with a median age of 67 years (range 23-83) were entered. A complete remission
      was achieved in seven patients, a partial remission was achieved in one patient
      for an overall response rate of 28% (8/28). There were four of 13 responders in
      MDS/AML patients and four of 15 in patients with MDS. The median duration of
      complete response was 7 months (range 2-10). Significant myelosuppression was
      universal and resulted in a high incidence of induction deaths (13/28) due to
      neutropenic-related infections. Extramedullary toxicity was mild and consisted of
      hypo-tension, fluid retention, hypoglycemia, diarrhea, nausea and vomiting. HHT
      given in this dose and schedule demonstrated limited activity in MDS and MDS/AML
      and was associated with prolonged pancytopenia and marrow hypoplasia in many
      patients. Administration of HHT at a lower dose or in combination with
      hematopoietic growth factors may lead to better results, but treatment with HHT
      as single agent at this dose and schedule is not currently recommended for these
      patients.

PMID- 8558936
TI  - Recombinant human interleukin-3 (rH IL-3) in combination with remission induction
      chemotherapy in patients with relapsed acute myelogenous leukemia (AML): a phase
      I/II study.
AB  - Patients with AML who relapse after an initial remission, have a poor prognosis.
      Administration of hemopoietic growth factors (HGFs) such as interleukin-3 (IL-3)
      during chemotherapy may result in an increased cell kill by cytotoxic agents. In
      addition, administration of IL-3 following chemotherapy may potentially
      accelerate hemopoietic recovery from chemotherapy-induced bone marrow hypoplasia.
      We performed an open labelled, phase I/II study in which patients received IL-3
      by continuous infusion from 24 h before the beginning of chemotherapy until day
      28. Chemotherapy included daunorubicin or mitoxantrone days 1-3 and cytarabine
      200 mg/m2 days 1-7. IL-3 was given at a dose of 5 microgram(s)/kg/day in 10
      patients, 7.5 microgram(s)/kg /day in six patients and 10 microgram(s)/kg/day in
      four patients. Complete remissions (CR) after one cycle of this treatment were
      obtained in 5/10 patients and 5 microgram(s)/ kg group, 2/6 in the 7.5
      microgram(s)/kg group and 3/4 in the 10 microgram(s)/kg group). Thus, 50% (10/20)
      of all individuals and 45% (5/11) of the elderly patients attained CR. Eight of
      20 patients entered PR, and 2/20 patients died during the hypoplastic phase from
      infectious complications. Neutrophils and platelets recovered to 0.5 x 10(9)/l at
      day 25 (median) and to 50 x 10(9)/l at day 32, respectively. Adverse events
      during IL-3 and concomitant chemotherapy were fluid retention (4/20), rash
      (14/20), bone pain (2/20), headache (10/20), chest pain (1/20), arthritis (1/20),
      fever and nausea. IL-3 (at the dose of 10 microgram(s)/kg) was discontinued in
      two patients because of side-effects (fluid retention, fever, rash and chest
      pain), and in two other patients the high IL-3 dose was tolerated with no
      problems for 29 days. Thus, IL-3 applied to patients with high-risk AML at
      dosages of 5-10 microgram(s)/kg is tolerated with acceptable toxicity and results
      in a satisfactory frequency of complete responses following a single treatment
      cycle.

PMID- 8558937
TI  - Expression of multidrug resistance-associated protein (MRP) mRNA in blast cells
      from acute myeloid leukemia (AML) patients.
AB  - A specific and quantitative reverse-transcription polymerase chain reaction (RT
      PCR) assay was developed for measuring the mRNA of the multidrug resistance
      associated protein (MRP). A region corresponding to bp 3897-4471 of MRP cDNA is
      amplified, which encompasses approximately half of the second nucleotide-binding
      domain (NBD2). In two multidrug resistant (MDR) sublines of the HL-60 human acute
      myeloid leukemia (AML) cell line which overexpress MRP but not P-glycoprotein,
      the assay detects elevated levels of MRP mRNA (4- to 8-fold) relative to the drug
      sensitive parental cells (designated HL-60/W). Blast cells from 24 patients with
      AML were also studied for MRP expression using this RT-PCR method. Expression of
      MRP was normalized for that of beta-actin in the blast cells, which was also
      determined by RT-PCR. All of these blast cell samples had MRP expression that was
      detectable after 35 PCR cycles. Eighteen of these patients samples had levels of
      expression of MRP mRNA equal to or less than that expressed by HL-60/W cells. In
      six patient blast cell specimens, the expression of MRP mRNA was up to 1.7-fold
      higher than that of HL-60/W cells. In 21 specimens, the steady-state
      intracellular accumulation of daunorubicin (1 microgram/ml, 3h) was also
      determined. The blast cells with MRP mRNA expression higher than HL-60/W had a
      lower median accumulation of daunorubicin compared to those whose MRP expression
      was less than HL-60/W, suggesting a functional defect in drug transport in the
      cells with higher MRP expression; a similar trend toward lower daunorubicin
      accumulation was also noted in the one-third of samples that displayed the
      highest expression of MDR1 mRNA (also determined by RT-PCR). These studies
      illustrate the range of expression of MRP in AML blast cell specimens. The
      identification of MRP overexpression in MDR AML cell lines and in some AML
      patient blast cells with low intracellular daunorubicin accumulation warrants
      further study of MRP as a component of clinical drug resistance in AML.

PMID- 8558938
TI  - Morphologic, immunologic, and cytogenetic classification of acute myeloid
      leukemia and myelodysplastic syndrome in childhood: a report from the Childrens
      Cancer Group.
AB  - The purposes of this report are to reaffirm concordance difficulties with the
      acute myeloid leukemia (AML) French-American-British (FAB) classification, to
      present the frequency of previously delineated AML syndromes in pediatric
      patients and to describe additional characteristic AML profiles utilizing
      composite morphologic, cytogenetic and immunophenotypic data. Profiles of 124
      children with acute myeloid leukemia (AML) and 13 children with myelodysplastic
      syndrome entered on the Childrens Cancer Group (CCG) pilot study CCG-2861 were
      examined. Concordance between institutions and reviewers for FAB designation was
      65%. Discordance was found principally between M1 and M2, M2 and M4, and M4 and
      M5. In 49% of marrow specimens, leukemic blasts expressed at least one T lineage
      related antigen; 24% expressed the B lineage-related antigen CD19. CDw14
      correlated with FAB M4 or M5 morphology and was the only surface antigen
      associated with a specific FAB subtype. Normal karyotypes were found for 15% of
      the 75 children with satisfactory karyotype preparations. Recurring aberrations,
      found in 76% of children, included t(15;17)(q22;q11), t(8;21)(q22;q22),
      inv(16)(p13q22), rearrangements of band 11q23, t(6;9) (p23;q34), trisomy 8 and
      monosomy 7. Results from this pilot study and from the current CCG randomized
      trial correlating morphology, immunophenotyping and cytogenetics, will help to
      classify AML into unique subgroups with differing clinical consequences or
      therapy requirements.

PMID- 8558939
TI  - Allopurinol inhibits de novo purine synthesis in lymphoblasts of children with
      acute lymphoblastic leukemia.
AB  - Allopurinol is used to prevent hyperuricemia in newly diagnosed patients with
      acute lymphoblastic leukemia (ALL). Although allopurinol has been shown to
      inhibit de novo purine synthesis (DNPS) in fibroblasts in vitro, this effect has
      not been assessed in ALL lymphoblasts. We assessed DNPS in ALL lymphoblasts in 46
      consecutive patients with ALL. DNPS was determined by 14C-formate incorporation
      in purine bases both at diagnosis (n = 46) and 44h after MTX therapy +/-
      allopurinol (n = 31). The 27 patients who had received no allopurinol prior to
      the diagnostic bone marrow aspirate had significantly higher rates of DNPS
      (median, 102 fmol new purines/nmol total purines/h) compared to the 12 patients
      who had received more than one dose of allopurinol (100 mg/m2 orally) (median,
      2.3 fmol/nmol/h; P < 0.001); the seven patients who received one dose of
      allopurinol had intermediate rates of DNPS (median, 58.5 fmol/nmol/h). Among
      patients who were evaluable for MTX effects at 44h (n = 31), the percent
      inhibition of DNPS was greater in the eight patients who received concomitant
      allopurinol (median, 100% inhibition) compared to the 23 patients who received
      only methotrexate therapy (median, 89% inhibition, P = 0.03). These data indicate
      that allopurinol suppresses may contribute to the decrease in circulating blasts
      in patients with newly diagnosed acute leukemias.

PMID- 8558940
TI  - Minimal residual disease detection in acute promyelocytic leukemia by reverse
      transcriptase PCR: evaluation of PML-RAR alpha and RAR alpha-PML assessment in
      patients who ultimately relapse.
AB  - RT-PCR assays used to detect acute promyelocytic leukemia (APL) are generally
      considered less sensitive than those for other hematological malignancies, such
      as CGL. Most patients with APL express del(17q)-derived RAR alpha-PML transcripts
      as well as the putative leukemogenic PML-RAR alpha associated with add(15q). We
      have found that a nested RT-PCR for RAR alpha-PML affords greater sensitivity
      than that for PML-RAR alpha, particularly in patients with the commonest
      breakpoint pattern. Therefore, we have evaluated both assays in parallel to
      monitor a group of 12 de novo APL patients who relapsed despite treatment with
      both all-trans retinoic acid (ATRA) and chemotherapy. 5' (bcr 3) breakpoints in
      PML were over represented among the group and three patients had complex
      cytogenetic abnormalities suggesting both factors may increase the risk of
      relapse. The RAR alpha-PML assay changed the PCR status of two patients in
      morphological remission; in both cases disease contamination of bone marrow
      harvest specimens was detected. Although parallel assessment of PML-RAR alpha and
      RAR alpha-PML can enhance minimal residual disease detection in APL, this study
      demonstrates that treatment strategies involving determination of PCR status post
      consolidation, even using RAR alpha-PML in addition to the more conventional PML
      RAR alpha assay will fail to identify all patients at risk of relapse. Whether
      the duration of PCR positivity is a helpful prognostic indicator in those
      patients who ultimately become PCR negative is being addressed by

PMID- 8558941
TI  - High levels of Ca(2+)-independent endonuclease activity capable of producing
      nucleosomal-size DNA fragmentation in non-adherent marrow mononuclear cells from
      patients with myelodysplastic syndromes and acute myelogenous leukemia.
AB  - The endogenous endonucleases capable of producing nucleosomal-size DNA
      fragmentation are considered candidates of the key enzyme of apoptosis. We
      examined these activities in the nuclear fraction of non-adherent marrow
      mononuclear cells (NonAd-MNCs) from patients with myelodysplastic syndromes (MDS)
      and acute myelogenous leukemia (AML) using a nuclear autodigestion method. We
      detected Ca2+/Mg(2+)-dependent endonuclease activity in all samples examined. In
      contrast, Ca(2+)-independent activity with the ability to produce nucleosomal
      size DNA fragmentation was found only in samples from a proportion of patients
      with MDS (12 of 26 consecutive cases) and all the patients with AML (n = 6), but
      not in the samples from control group patients (n = 10). This activity was
      correlated with the percentage of bone marrow (BM) blast cells to some extent.
      Although the levels of these endogenous endonuclease activities seem not to be
      correlated directly with the susceptibility of the cells to apoptosis, we
      postulate that the Ca(2+)-independent endonuclease activity may be associated
      with apoptosis and/or cell proliferation. Further follow-up study of these
      patients may be meaningful to clarify the prognostic significance of the Ca(2+)
      independent endonuclease activity in patients with MDS.

PMID- 8558942
TI  - 11q23 rearrangements in acute leukemia.
AB  - The MLL gene, located at chromosome 11, band q23, is frequently disrupted by a
      variety of chromosomal rearrangements that occur in acute lymphoblastic leukemias
      and in a subset of de novo and secondary acute myeloid leukemias. In both
      scenarios, MLL rearrangements are associated with distinct clinical features and
      a poor prognosis. MLL encodes a large protein (MLL) that shares homology with the
      Drosophila trithorax protein. 11q23 translocations result in the generation of a
      series of acute leukemia-specific chimeric proteins that contain the N-terminus
      of MLL and are thought to be crucial to leukemogenesis. In this article, we
      review the structural features of the MLL fusion proteins as well as the clinical
      features and molecular diagnosis of acute leukemias containing MLL arrangements.

PMID- 8558943
TI  - Mutant ras promotes haemopoietic cell proliferation or differentiation in a cell
      specific manner.
AB  - The ras gene products play a fundamental role in signal transduction in
      haemopoiesis. In this study, we have examined the effects of ras upon
      haemopoietic cell proliferation and differentiation, using two human cell lines
      which represent different stages of haemopoietic cell maturation. When a mutant
      H12-ras gene (codon 12: gly-->asp) was expressed in the monoblastic cell line,
      U937, marked inhibition of growth was seen together with morphological,
      functional and immunophenotypic evidence of monocytic maturation. Infection of
      U937 cells with a c-myc retrovirus produced similar changes strongly suggesting
      that Myc plays an important role in this action of Ras. By contrast, expression
      of H12-ras promoted factor-independent growth of the multipotent cell line, TF-1.
      Furthermore, mutant ras dramatically enhanced the growth of TF-1 cells in the
      presence of added GM-CSF or erythropoietin, but did not influence the state of
      differentiation of these cells. These data clearly indicate that in haemopoietic
      cells, Ras may promote either proliferation or differentiation depending upon
      cell type and/or state of maturation.

PMID- 8558944
TI  - Coexpression of thrombopoietin and c-mpl genes in human acute myeloblastic
      leukemia cells.
AB  - Thrombopoietin (TPO) is a recently identified hematopoietic growth factor that is
      essential for the growth and development of megakaryocytes. We have previously
      shown that TPO induces proliferation of acute myeloblastic leukemia (AML) cells
      in vitro. In this study, we have examined the expression of TPO and its receptor
      c-mpl in a series of AML cases and human leukemia cell lines. The mRNA
      transcripts of TPO were detectable in 18 of 50 AML cases and in some myeloid
      leukemia cell lines (HEL, M07E and CMK) by means of reverse transcriptase
      polymerase chain reaction (RT-PCR). In addition, TPO transcripts were coexpressed
      with c-mpl transcripts in 10 of 50 AML cases and in HEL, M07E and CMK cells. With
      regard to the French-American-British (FAB) classification, coexpression OF TPO
      and c-mpl was observed with high frequency in AML cases of M7-type. Despite the
      TPO expression in a substantial fraction of leukemia cells, biological activity
      of TPO was not found in the conditioned medium that was obtained from cultivation
      of TPO mRNA-positive leukemia cells. These results suggest that TPO may not
      commonly participate in the abnormal growth of AML cells as an extracellular
      autocrine growth factor.

PMID- 8558945
TI  - All-trans retinoic acid rapidly decreases cathepsin G synthesis and mRNA
      expression in acute promyelocytic leukemia.
AB  - The cells from patients with acute promyelocytic leukemia (AML M3) undergo
      terminal differentiation when treated with all-trans retinoic acid (ATRA). We
      have analyzed the expression of the mRNA for cathepsin G, a promyelocyte stage
      specific transcript, in the leukemia and in retinoic acid responsive cell lines.
      We showed that the transcript is perpetually synthesized in patients' cells and
      that it rapidly disappears when the cells are treated with ATRA. In ATRA
      sensitive (HL-60, NB4) cell lines and an ATRA-resistant (HL-60R) cell line we
      have shown that this process is dependent on proteins synthesized during the
      first 6h of ATRA-triggered differentiation and may involve both pre- and post
      transcriptional mechanisms. A corresponding decrease in cathepsin G protein
      synthesis then follows. These findings indicate that the maturation arrest in AML
      M3 results in cells that may constitutively continue to produce proteins whose
      production is temporally confined during normal hemopoiesis. This would explain
      the elevated plasma-free serine protease activity we have demonstrated in this
      disease, and has implications for both the coagulopathy and the 'retinoic acid
      syndrome' in AML M3.

PMID- 8558946
TI  - An approach to intelligent ischaemia monitoring.
AB  - The paper describes an approach to intelligent ischaemia event detection based on
      ECG ST-T segment analysis. ST-T trends are processed by means of a Bayesian
      forecasting approach using the multistate Kalman filter. A complete procedure,
      intended for use in CCU/ICU monitoring areas, is proposed, in order to give the
      clinician an intelligent monitoring tool. The approach serves to describe trends
      and their changes in a symbolic way. A novel aspect is its ability to observe
      certain features of ST-T elevation/depression not detected by other means, and to
      reject artefacts and erroneous events. A sensitivity of 89.58% and a predictivity
      of 84.31% are obtained on selected records of the European ST-T database. Using a
      restriction on event amplitude, the predictivity is raised to 95.55%. An
      ischaemia sensitivity index of 1.2 was determined. The method has been shown to
      be a robust and practical trend analysis tool, and seems to be appropriate for
      numeric/symbolic transformations in next-generation intelligent monitoring
      systems.

PMID- 8558947
TI  - Hybrid time-frequency adaptive filtering for the recovery of ventricular late
      potentials.
AB  - Ventricular late potentials are small ECG components that have significant
      diagnostic importance. Temporal averaging is used to recover these signals from
      high levels of background noise, but is not the optimum approach. A new form of
      hybrid time-frequency adaptive filtering is introduced that is based on signal
      division into a series of frequency bands. This technique is able to process the
      averaged data further and to reduce significantly the noise levels beyond that
      achieved by simple averaging. Examples of the processing are shown and its
      applicability is discussed.

PMID- 8558948
TI  - Modelling selective activation of small myelinated nerve fibres using a monopolar
      point electrode.
AB  - The aim of this study is to investigate theoretically the possibility for
      activation of small myelinated nerve fibres without activating larger ones when
      stimulating a nerve fibre bundle using a monopolar point electrode. Therefore,
      the sensitivity of excitation and blocking threshold currents of nerve fibres to
      fibre diameter, electrode-fibre distance and pulse duration has been simulated by
      a computer model. A simple infinite, homogeneous volume conductor and a cathodal
      point source were used in combination with a model representing the electrical
      properties of a myelinated nerve fibre. The results show that selective
      activation of small myelinated fibres may be possible in a region at some
      distance from the electrode.

PMID- 8558949
TI  - Optimisation of transcutaneous cardiac pacing by three-dimensional finite element
      modelling of the human thorax.
AB  - The goal of the study is to determine by finite element analysis (FE) the optimal
      electrode placement, size and electrolyte resistivity that minimise the pain
      experienced by patients during successful transcutaneous cardiac pacing (TCP).
      The three-dimensional FE model generated for this purpose has 55,388 nodes,
      50,913 hexahedral elements and simulated 16 different organs and tissues, as well
      as the properties of the electrolyte. The model uses a non-uniform mesh with an
      average spatial resolution of 0.8 cm in all three dimensions. To validate this
      model, the voltage across 3 cm2 Ag-AgCl electrodes is measured when currents of 5
      mA at 50 kHz are injected into a subject's thorax through the same electrodes.
      For the same electrode placements and sizes and the same injected current, the FE
      analysis produced results in good agreement with the experimental data. The
      optimisation analysis tested seven different electrode placements, five different
      electrode sizes and six different electrolyte resistivities. The analysis
      indicates that the anterior-posterior electrode placement, electrode sizes of
      about 90 cm2 and electrolytes with resistivity of about 800 omega.cm yield the
      most uniform current distribution through the skin, thus having the best chances
      to minimise the pain delivered to the patient during successful TCP. The anterior
      anterior electrode placement is the second most efficient.

PMID- 8558950
TI  - Computer-controlled mechanical lung model for application in pulmonary function
      studies.
AB  - A computer controlled mechanical lung model has been developed for testing lung
      function equipment, validation of computer programs and simulation of impaired
      pulmonary mechanics. The construction, function and some applications are
      described. The physical model is constructed from two bellows and a pipe system
      representing the alveolar lung compartments of both lungs and airways,
      respectively. The bellows are surrounded by water simulating pleural and
      interstitial space. Volume changes of the bellows are accomplished via the fluid
      by a piston. The piston is driven by a servo-controlled electrical motor whose
      input is generated by a microcomputer. A wide range of breathing patterns can be
      simulated. The pipe system representing the trachea connects both bellows to the
      ambient air and is provided with exchangeable parts with known resistance. A
      compressible element (CE) can be inserted into the pipe system. The fluid-filled
      space around the CE is connected with the water compartment around the bellows;
      The CE is made from a stretched Penrose drain. The outlet of the pipe system can
      be interrupted at the command of an external microcomputer system. An automatic
      sequence of measurements can be programmed and is executed without the
      interaction of a technician.

PMID- 8558951
TI  - Multi-frequency static imaging in electrical impedance tomography: Part 1.
      Instrumentation requirements.
AB  - Static images of the human body using electrical impedance tomography techniques
      can be obtained by measuring at two or more different frequencies. The
      frequencies used depend on the application, and their selection depends on the
      frequency behaviour of the impedance for the target tissue. An analysis using
      available data and theoretical models for tissue impedance yields the expected
      impedance and boundary voltage changes, therefore setting the measurement
      instrument specifications. The instrument errors produced by different sources
      are analysed, and, from this analysis it is possible to determine the feasibility
      of building the instrument, the limit values for some parameters (or components)
      and indications on the most suitable design of critical parts. This analysis also
      shows what kinds of error can be expected in the reconstructed images. It is
      concluded that it is possible to build an instrument with limited errors,
      allowing static images to be obtained. An instrument has been built that meets
      some of the design requirements and fails in others because of technological
      problems. In vivo images obtained with this instrument will be presented in Part
      2 of this work.

PMID- 8558952
TI  - Influence of materials and geometry on fields produced by cochlear electrode
      arrays.
AB  - Most cochlear prostheses use multichannel electrode arrays implanted in the scala
      tympani to generate multiple parallel channels of activity in the tonotopically
      mapped auditory nerve. Various materials and geometrical arrangements of contacts
      and locations within the scala tympani have been used, resulting in substantial
      differences in the required stimulus strengths and resulting spatial
      distributions of neural activity. Activated iridium (AIR) permits systematic
      adjustment of its metal-electrolyte interface properties by changing the degree
      of electrochemical activation. Planar equivalent models of bipolar cochlear
      electrode geometries using iridium have been built, and their impedance magnitude
      and phase versus frequency for various degrees of activation have been
      characterised. The electrical fields produced at various distances from bipolar
      contacts in saline are measured. In comparison to platinum and unactivated
      iridium, AIR provides a much lower metal-electrolyte interfacial impedance. When
      two AIR contacts are placed with their edges close together, the resulting field
      distributions are determined largely by the high (but safe) current densities at
      their apposed edges rather than the overall extent of the contacts. These edge
      effects permit a novel design for a bipolar array that produces N channels of
      radially distributed, non-overlapping fields and that requires only N + 1
      contacts.

PMID- 8558953
TI  - Design optimisation of planar electrolytic conductivity sensors.
AB  - Planar conductivity sensors are the subject of increasing interest as basic
      transducers for biosensors. The high degree of control of the performance
      characteristics undoubtedly forms an important argument in favour of conductivity
      based sensing. The paper provides an outline of the design rules to be followed
      if an optimal design of a planar conductivity cell is required. Based on a
      simplified model, it is shown that the required accuracy establishes a lower
      limit to the overall sensor dimensions. This lower limit is expressed as a
      minimum longitudinal path length necessary to obtain the desired accuracy. Given
      an available area, the optimum ratio of electrode-width over inter-electrode
      spacing for a basic two-electrode structure is shown to be close to unity.
      Furthermore, it is shown that the decomposition of the two electrodes into an
      interdigitated structure decreases the accuracy of the device if all other
      parameters are considered constant. If the sensing region has to be limited to
      within a thin sensitive layer, the splitting is proposed of one of the electrodes
      into a compound electrode. The optimum lay-out of this compound structure is
      calculated as a function of the layer thickness.

PMID- 8558955
TI  - The concept of half-life of hormone.

PMID- 8558956
TI  - In vivo measurement of arterial pre-tension.

PMID- 8558954
TI  - Haemocompatibility of invasive sensors.
AB  - In recent years the importance and utilisation of invasive chemical sensors have
      increased, especially in respect to their function and behaviour in a biological
      environment. This review aims to highlight the development of various sensors and
      reflect on the problems which can occur when the sensors come into contact with
      blood. Thus their haemocompatibility is a key area of importance. A clear
      understanding of their interaction with plasma proteins at the point of interface
      is fundamental as this determines their ultimate capability to function safely
      and effectively. There is also an overview of various techniques that have been
      developed, together with a broad summary of inherent problems which may arise
      when aiming to improve the haemocompatibility of invasive sensors for in vivo
      applications.

PMID- 8558957
TI  - Microprocessor-based physiological signal monitoring and recording system for
      ambulatory subjects.

PMID- 8558958
TI  - Linearisation of a urinary flow transducer.

PMID- 8558959
TI  - Buckling of elastic tubes: study of highly compliant device.

PMID- 8558960
TI  - ANN compression of morphologically similar ECG complexes.
AB  - A compression algorithm for electrocardiogram signals is presented, based on an
      auto-associative neural network. Issues of weight and activation coding are
      considered, and compression performances of various network sizes are compared. A
      unique feature is the performance improvement achieved using DC level removal. A
      comparison with existing techniques is provided.

PMID- 8558961
TI  - [Prospective study of the incidence of post-transfusion hepatitis after the
      exclusion of donors positive for anti-HCV ELISA 2].
AB  - BACKGROUND: The incidence of post transfusional hepatitis (PTH) after the
      exclusion of anti-HCV ELISA 2 positive donors is not well known. The aim of this
      study was to determine the incidence and type of PTH in 113 post transfused
      patients. METHODS: A post transfusional follow up was performed for at least one
      year with periodic controls of transaminase levels. When an increase in GPT level
      compatible with PTH was demonstrated investigation of all the virus related with
      the transfusion was carried out in both the donor and the transfused subject:
      HAV, HCV, HEV, HBV and CMV. RESULTS: Four cases (3.5%) were detected which
      fulfilled the PTH criteria with the following characteristics: short period of
      time between transfusion and the increase in GPT level, moderate GPT increase,
      moderate clinical expression and good evolution. In all the cases the viral study
      was negative and other non viral possibilities were eliminated. CONCLUSIONS:
      Transfusions are currently relatively safe and the increase in transaminases may
      not be related with transfusion.

PMID- 8558962
TI  - [Effectiveness of influenza vaccine in the elderly. A critical review of the
      bibliography].
AB  - BACKGROUND: The acceptance of influenza vaccine has been slow as doubts about its
      effectiveness persist. The goal of this study is to review the existing evidence
      on influenza vaccine effectiveness in preventing pneumonia and influenza
      hospitalizations in non institutionalized elderly. METHODS: We have conducted a
      search in MEDLINE, including a period between 1984 and 1994, and of cross
      references, between 1980 and 1994. Twelve studies have been identified and valued
      independently by the authors. The results are combined through a graphic
      representation and the quantitative method proposed by Woolf. RESULTS: Four
      studies have been excluded; two, because they did not satisfy the comparability
      principle; one, because it was a publication already published; and one because
      of small numbers. According to the graphic method, influenza vaccine prevents
      between 29 and 51 percent of pneumonia and influenza hospitalizations in the non
      institutionalized elderly. When results are integrated by the quantitative
      method, the odds ratio is 0.63 (CI 95%, 0.54 to 0.72). The percentage of
      pneumonia and influenza hospitalizations prevented by the influenza vaccine
      equals 37.40% (CI 95%, 27.81% to 45.72%) in the vaccinated. CONCLUSIONS: The
      annual influenza immunization of those 65 years old or older is an effective
      primary prevention strategy.

PMID- 8558963
TI  - [The COMBELL project. Analysis of the medical clinical competence].
AB  - BACKGROUND: The most frequent tests for evaluate medical education in Spain, do
      not analyze clinical competence. The aims of this project was to introduce a
      method for the assessment of clinical skills using the simulation methodology
      with standardized patients. METHODS: All 83 first-year medical residents were
      evaluated. Three evaluation exercises were used in all study. The first was 10
      standardized patients encounters, the second was 100 multiple choice questions,
      and the third 60 clinical images. Sixty-four last year medical students were
      evaluated using the same 10 standardized patients. RESULTS: The global mean score
      for the residents was 56.7% for all the encounters, and was lower in physical
      examination and patients notes. The global mean score for the students was 57.1%
      and was also lower in physical examination. We did not find correlations between
      clinical competence assessment, multiple choice-questions, MIR exam and clinical
      images. CONCLUSIONS: Our results show that: this assessment method was
      successful; the clinical competence levels of our residents and students, and the
      lack of statistical correlation between this method and other methods, which,
      basically analyze cognitive capacities.

PMID- 8558964
TI  - [Penetration and intracellular activity of antimicrobial agents. A new
      pharmacologic parameter?].

PMID- 8558965
TI  - [Theory and practice teaching: a relevant classification?].

PMID- 8558966
TI  - [Iatrogenic hyperthyroidism. Report of an outbreak].
AB  - The clinical observation of a series of 30 patients (age 29.6 +/- 9.8 years, 29
      females and 1 male) who were remitted for evaluation of a thyroid dysfunction
      with a decrease in TSH and free thyroxin with clinical symptoms of
      hyperthyroidism and absence of goiter or exophthalmous is presented. Most of the
      patients (90%) had no family or personal history of previous thyroid disease.
      Anamnesis demonstrated the previous ingestion of uncommercialized prepared weight
      losers, dispensed in different areas off the pharmacy offices. Seventy-three
      percent of the patients had received the treatment from the same source
      (prescriber). In most of the cases (28 out of 30) normalization was observed in
      thyroid function tests. The demonstrated inefficacy of this medication as well as
      the health care importance of the problem are discussed.

PMID- 8558967
TI  - [Lung toxicity of cancer treatment].

PMID- 8558968
TI  - [Asthenia, weight loss, and left supraclavicular tumor in a 31-year-old male].

PMID- 8558969
TI  - [Capillaria philippinensis diarrhea].

PMID- 8558970
TI  - [Smoking and arterial blood pressure among adolescents in Girona].

PMID- 8558971
TI  - [Delirium in an elderly population hospitalized at a general hospital].

PMID- 8558972
TI  - [Self esteem, clinical protocols, and protocollized dissent. Task Force of Care
      Quality].

PMID- 8558973
TI  - [When the residents leave].

PMID- 8558974
TI  - [Lithium: therapeutic usefulness and treatment of lithium poisoning].

PMID- 8558975
TI  - [Carotid atherosclerosis evaluated by two-dimensional ultrasonography in patients
      with primary hypercholesterolemia].
AB  - BACKGROUND: Two-dimension ultrasonography permits to noninvasively quantify
      extracoronary atherosclerosis. The objective of this study was to assess
      preclinical atherosclerosis of the extracranial carotid arteries in patients with
      primary hypercholesterolemia. METHODS: Lipid and nonlipid cardiovascular risk
      factors were evaluated in 206 patients with dyslipidemia (127 men and 79 women,
      mean age 49 years, range 18-75), and a multifactorial cardiovascular risk profile
      was constructed for each patient. Ultrasound measurements of the intima-media
      thickness in the common carotid artery of each side were taken, and the number
      and height of any atheroma plaques present were quantified. RESULTS: Asymptomatic
      plaques were found in 120 patients (58%), and were more frequent in men than in
      women (65 vs 47%, p = 0.009), and in patients with than in those without prior
      coronary heart disease (80 vs 50%, p < 0.001). Both intimal thickening,
      indicative of early atherosclerosis, and the extent of arterial wall involvement
      with plaques, which represents an advanced stage of the disease, increased
      significantly with age and with increasing multifactorial cardiovascular risk,
      reflecting a positive relation between signs of atherosclerosis and the burden of
      risk factors. Intima-media thickness also increased with increasing plaque score,
      indicating the generalization of atherosclerosis. CONCLUSIONS: The high
      prevalence of preclinical carotid atherosclerosis confirms the atherogenic risk
      of primary dyslipidemias. The relation between carotid lesions and both coronary
      heart disease and multifactorial risk supports the validity of arterial
      ultrasound studies for cardiovascular risk prediction.

PMID- 8558976
TI  - [Transmembrane Na+ transport kinetics in arterial hypertension: relations with
      vascular risk parameters].
AB  - BACKGROUND: To characterize the possible existence of kinetic anomalies of four
      erythrocyte membrane sodium transport systems in a group of essential
      hypertensive patients, and to study the clinical and biochemical profile of those
      with anomalies. METHODS: We studied 33 essential hypertensive patients and 33
      normotensive controls. The kinetics (maximal rate and apparent dissociation
      constant for internal sodium) of Na(+)-K+ pump, Na(+)-K(+)-Cl- cotransport and
      Na(+)-Li+ countertransport was calculated after a sodium loading procedure,
      according to the methods of Garay; the passive Na+ permeability was also
      determined. RESULTS: The studied kinetic parameters were not significantly
      different in both groups. Nevertheless, we found a group of hypertensive patients
      with some transport abnormalities: increased intracellular sodium (9.1%),
      accelerated Na+ passive permeability (9.1%), lower activity of the Na(+)-K+ pump
      (7.1%) and the Na(+)-K(+)-Cl- cotransport (4%) and an increased maximal rate of
      the Na(+)-Li+ countertransport (11.8%). Na+Li+ countertransport activity was
      statistically related to plasma levels of urea, creatinine, glucose and LDL
      cholesterol, and the activity of the Na(+)-K(+)-Cl- cotransport was related to
      plasma uric acid. The hypertensive patients with sodium transport anomalies
      showed higher body mass index, uric acid plasma levels and atherogenic index than
      those without these kind of anomalies, and they also showed lowered HDL
      cholesterol plasma levels. CONCLUSIONS: A small group of essential hypertensive
      patients (around 31%) show kinetic alterations of sodium transport systems. There
      is a relation between Na(+)-Li+ countertransport activity and some cardiovascular
      risk parameters. Hypertensive patients with transport anomalies are a group with
      an increased cardiovascular risk.

PMID- 8558977
TI  - [Is there any association between Helicobacter pylori infection and peptic
      esophagitis?].
AB  - BACKGROUND: To describe the prevalence of Helicobacter pylori infection in
      patients with reflux esophagitis, and compare it with that in patients with
      normal endoscopy. METHODS: Fifty-five patients with endoscopic peptic esophagitis
      and 55 symptomatic patients with normal endoscopy were studied. Age and sex
      distribution were similar in both groups. At endoscopy biopsy specimens were
      taken from gastric antrum and body (H & E, Gram stain and culture). RESULTS: H.
      pylori was found in 74.5% (95% CI = 62-84%) of patients with reflux esophagitis,
      and in 76.4% (CI = 64-86%) of cases with normal endoscopy (a non-significant
      difference). In patients with esophagitis and H. pylori infection normal
      histologic antral mucosa was observed in 7.3% of cases (CI = 2.5-19.4%). In
      patients with normal endoscopy the corresponding figure was 4.8% (CI = 1.3-15.8%)
      (a non-significant difference). At gastric body from infected patients the
      percentages of patients with normal histologic mucosa was 29.3% (n = 12) and
      23.8% (n = 10), in both groups respectively. CONCLUSIONS: The prevalence of H.
      pylori infection in patients with reflux esophagitis was 74.5%, and no difference
      was observed when comparing with infection rate in patients with normal endoscopy
      (76.4%). Therefore, a non-significant association was found between this
      esophageal disorder and H. pylori infection.

PMID- 8558978
TI  - [Diagnosis of Sjogren's syndrome].

PMID- 8558979
TI  - [Farewell].

PMID- 8558980
TI  - [Celiac disease with occipital calcifications: 2 late cases].
AB  - The association of celiac disease, epilepsy and occipital calcifications with
      initial clinical manifestations of epilepsy during the first two decades of life
      with an often progressive and variable course and clinical expression of
      malabsorption has recently been described. Two cases of celiac disease with
      occipital calcifications and a presentation with neurologic symptoms in adulthood
      are reported. The first case is that of a 40-year-old male who presented
      recurrent and alternating pure brachial monoparesis and later acute abdominal
      pain following which celiac sprue was diagnosed. The second case is that of a 53
      year-old woman diagnosed with celiac sprue 20 years before, presenting permanent
      myoclonus in the lower limbs which were progressive in severity, ataxic march and
      generalized tonoclonic seizures. Both patients had bilateral occipital
      calcifications on CT and celiac disease was demonstrated on biopsy. The first
      case also showed marked signal alteration in the white matter on MRI. Celiac
      disease with cerebral calcifications presents also in adulthood with atypical
      clinical manifestations. Suspicion of celiac disease may be confirmed by non
      invasive methods such as antigliadin and antiendomysium antibody determination.
      CT imaging is characteristic.

PMID- 8558981
TI  - [Radiotherapeutic oncology: a little known specialty].

PMID- 8558982
TI  - [49-year-old man with chronic diarrhea and anemia].

PMID- 8558983
TI  - [Granulomatous pneumonitis: a clinical manifestation and atypical pathology of
      pneumocystosis in AIDS].

PMID- 8558984
TI  - [Parkinsonism secondary to the use of sertraline].

PMID- 8558985
TI  - [Bilateral primary adrenal lymphoma with atypical presentation as an addisonian
      crisis].

PMID- 8558986
TI  - [Familial complement deficiency in a patient with recurrent meningococcal
      sepsis].

PMID- 8558987
TI  - [The booster effect or the "empuje" effect: it is better to use an anglicism than
      a confusing translation].

PMID- 8558988
TI  - Peptide, peptidomimetic, and organic synthetic combinatorial libraries.

PMID- 8558989
TI  - Recent development in the design of antiviral agents.

PMID- 8558990
TI  - TNF and AIDS: two sides of the same coin?

PMID- 8558991
TI  - What the doctor thought and did: Sir James Crichton-Browne (1840-1938).

PMID- 8558992
TI  - "That puzleing problem": Isaac Newton and the political physiology of self.

PMID- 8558994
TI  - Malpighi's De polypo cordis: an annotated translation.

PMID- 8558993
TI  - What's in a name? Henry Dale and adrenaline, 1906.

PMID- 8558996
TI  - [Reconstruction of bile duct injuries].

PMID- 8558995
TI  - John Evelyn's tables of veins and arteries: a rediscovered letter.

PMID- 8558997
TI  - A new technique for reconstruction of the common bile duct after severe injury by
      laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy involves a higher incidence of severe common bile
      duct injury than did open cholecystectomy. The severe injuries most often result
      from technical problems and inadequate exposure. Reconstruction of the bile duct
      is then possible provided that an immediate diagnosis is made and an appropriate
      surgical technique is applied. The report focuses on a new method of
      reconstruction of the common bile duct by interposition of a small jejunal
      conduit. The procedure was performed in five patients with severe bile duct
      injury (Bismuth class 3-4) that occurred during laparoscopic cholecystectomy. The
      outcome after follow-up periods of 9 months to more than 2 years is promising.
      This method of reconstruction is therefore recommended for severe forms of bile
      duct injury.

PMID- 8558998
TI  - [Compartment syndrome. Frequently missed, with severe sequelae].
AB  - Experience and late results in patients with a compartment syndrome which was
      either missed or diagnosed too late are reported. In the case of 14 patients we
      were consulted after a delay of 24 h, in another three patients 48 h after the
      causative event. At that time the diseased extremity was severely swollen,
      blistered and extremely painful. Ten patients presented with loss of sensitivity;
      in eight the peripheral pulses were not palpable. CPK was elevated in nine
      patients (up to 30,000); in six patients CPK was not determined. Causative
      factors included vascular occlusion (n = 6), paravenous infusions or injections
      (n = 4), compression in heroin or alcohol abusers (n = 4) and infections
      secondary to i.m. injections, sepsis or snake bites (n = 4). One patient
      developed a compartment syndrome after the closure of a muscular hernia. The late
      results were sobering: eight limbs had to be amputated, another 13 showed muscle
      necrosis necessitating necrosectomy, and both transitory and persistent median,
      ulnar, radial and peroneal nerve damage was observed. Our experience shows that
      dermatofasciotomy should be done on a more generous scale, because it obviously
      prevents sequelae and because the late complications following inadequately
      treated compartment syndromes are grave.

PMID- 8558999
TI  - [Surgical therapy of hepatoblastoma in childhood].
AB  - Hepatoblastoma is a rare but highly malignant liver tumour, predominantly
      occurring during early childhood. Clinical data of 71 children treated from 1988
      to 1993 according to the protocol of the multicentre liver tumour study (HB89) of
      the German Society for Paediatric Oncology and Haematology were evaluated to
      assess the effects of surgical therapy in these patients. The protocol prescribed
      an initial laparotomy for all children with a liver tumour, except for infants
      with distant metastases and a high serum-alpha-fetoprotein; for small
      hepatoblastomas confined to one liver lobe primary resection by a lobectomy; and
      for those extending into both lobes and metastasizing tumours tumour reductive
      chemotherapy including ifosfamide, cisplatin and adriamycin (IPA), preparatory to
      resection at second-look surgery. All patients received adjuvant IPA chemotherapy
      after tumour resection. In 20 of the 71 cases, the hepatoblastomas were
      completely resected at initial laparotomy (stage I), while in 6 cases microscopic
      residues were left (stage II). In 38 of 45 children with extended hepatoblastomas
      (stage III, 38 patients) or distant metastases (stage IV, 7 patients) the tumour
      was resected during later surgery, and 1 patient received a liver transplant.
      Thus, the overall resection rate was 92% (65 of 71 hepatoblastomas). After a
      median follow-up of 3.8 years (range 1.0-5.9 years), 53 (75%) of the patients
      were tumor-free and 18 (25%) had died. Recurrence-free survival was 100% for
      stage I, 50% for stage II, 71% for stage III and 29% for stage IV patients (P =
      0.0009).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559000
TI  - [Solitary glomus tumors of the hand. A clinico-pathologic evaluation study].
AB  - The incidence of recurrence following surgical treatment of solitary tumours of
      the hand ranges from 12% to 50%. Examination of the reports in the literature
      reveals that different methods of histological typing have been used and that
      most of the publications available are case reports or refer to studies of small
      numbers of patients, so that direct adequate comparison of the rates in the
      literature is not possible. In an attempt to find out the reasons for local
      recurrence of retrospective clinicopathological study was performed. All
      histological specimens examined within one decade were analysed. The tumours they
      were taken from included 46 glomus tumours (female: male ratio 28:18, age range 9
      82, average 52.3 years) of different locations, 30 of them affecting the upper
      extremity. We had operated on 13 solitary, digitopalmar glomus tumours (8
      vascular type, 3 epitheloid solit type, 1 myxoid, 1 neural) in our institution,
      in most cases with the aid of either a magnifying lens or an operating
      microscope. The mean follow-up period was 76 months, and we had no recurrences.
      Therefore, we conclude that regardless of the histological type, optical
      magnification during surgical resection of solitary glomus tumours of the hand
      prevents recurrences. In our opinion, early recurrences are due to incomplete
      excision of tumours of the types mentioned above or to misdiagnosis because of
      the multiple forms of glomus tumours that can occur, especially during childhood.

PMID- 8559001
TI  - [Orthograde intestinal irrigation or Fordtran solution for bowel preparation in
      elective colorectal surgery. Prospective outcome study].
AB  - In a prospective cohort study, which was carried out at the department for
      abdominal surgery of the university of Mainz from June to December 1993, two
      methods of bowel preparation for elective colorectal surgery were compared: oral
      bowel preparation with Fordtran a new polyethylene glycol solution (63 patients),
      and whole-gut lavage with Ringer's solution (37 patients). The serum chloride
      levels and the bodyweight increased significantly more in the whole-gut lavage
      group. These patients also showed a higher frequency of vomiting during bowel
      preparation. Neither the bowel cleansing effect nor the postoperative
      complications differed significantly between the two groups. Owing to these
      results, the better patient acceptance, and the easier handling and lower costs
      of PEG solution, we recommend this method of preoperative bowel preparation for
      elective colorectal surgery.

PMID- 8559002
TI  - [Local recurrence of soft tissue sarcoma of the extremities and trunk].
AB  - Soft tissue sarcomas (STS) tend to recur locally. In a series of 140 patients
      operated on during the past two decades with STS of the extremities and trunk,
      prognostic factors influencing local recurrence were determined. Statistical
      significance was evaluated for the quality of surgical resection (P < 0.001),
      regional positive lymph nodes (P = 0.03), and adjuvant radiotherapy (P = 0.01)
      [for resection without wide margins (R1) and low-grade (G3) tumors]. In 1988, the
      surgical procedure was standardized. After 1987, local recurrence decreased
      significantly (P < 0.001). In subfascial tumors, local recurrence occurred far
      less in cases of compartmental resection than with wide excision. These data
      indicate that the course of patients with STS can be beneficially influenced by
      optimal therapy. Resection with wide margins in all three dimensions is the aim
      of sarcoma surgery. Postoperative radiation therapy is indicated in the case of
      R1 resection.

PMID- 8559003
TI  - [Nonparasitic liver cysts. Overview of therapy with long-term results].
AB  - Symptomatic nonparasitic cysts of the liver require surgical intervention.
      Seventy-one patients were treated between 1977 and 1993 at the Department of
      General Surgery, University of Vienna. Different surgical treatments were
      compared with regard to complications and recurrence. Interventional puncture led
      to recurrences in nearly all cases and represents only a palliative procedure.
      Surgical treatment consisted of either laparoscopic (n = 7) or conventional (n =
      44) fenestration or excision. The rates of recurrence did not differ
      significantly (14% vs 9%). The laparoscopic procedure is successful not only in
      polycystic disease but also in solitary cysts. Wide deroofing and excision were
      equally effective. Laparoscopic therapy should be tried in all cysts initially,
      because it causes less stress than celiotomy. Because of the small number of
      laparoscopically treated patients in the literature and in the authors' own
      experience, the significance of the difference in outcome between the two methods
      could not be established. In more patients, further investigations should be
      carried out to ascertain whether the laparoscopic method is superior regarding
      surgical stress and recurrence. Cystojejunostomy (n = 3) and hepatic resection (n
      = 2) are reserved for special indications. One homologous liver transplantation
      was successfully carried out 6 months after cystojejunostomy because of a
      cholangiocellular carcinoma. Frequent postoperative ascites represented a
      persistent problem in only one patient. Two of three cases of postoperative
      infection with intraabdominal abscesses led to death. Altogether, 16 patients
      died, including seven because of malignancy and three because of septic
      complications of a Potter III syndrome.

PMID- 8559004
TI  - [Benign pleural mesothelioma. Report of 2 cases].
AB  - We report two cases of benign pleura mesothelioma. We compare our pre-, intra-
      and postoperative findings with other reports in the literature. This tumor is
      rare. The patients have few symptoms. Large tumors may cause hypoglycemia. The
      treatment of choice is complete resection of the tumor. The prognosis is good.

PMID- 8559005
TI  - Malignant schwannoma of the breast.
AB  - Malignant schwannoma (MS) is a tumor of the Schwann or nerve sheath cells, most
      frequently occurring in the lower and upper extremities, trunk and head region.
      We report the third known case of MS of the breast, which occurred in a 27-year
      old woman. The palpable tumor, about 1.2 cm in diameter, was localized in the
      upper inner quadrant of the right breast. After ultrasonography, mammography and
      fine needle aspiration cytology, the tumor was removed surgically.

PMID- 8559006
TI  - [Epitheloid osteosarcoma. Differential diagnostic problems].
AB  - The case of a 23-year-old female patient suffering from a rare variety of
      osteosarcoma of the distal femur with epithelial differentiation and only traces
      of osteoid is reported. The tumour cells reacted strongly to antibodies against
      vimentin. Metastases were found in the fifth rib and the right kidney. There was
      no response to chemotherapy. One year after implantation of a tumour prosthesis
      of the knee a thigh amputation was necessary because of a local failure. The
      patient died 2.5 years after the tumour had initially been diagnosed. Other
      reports of this rare type of epitheloid osteosarcoma illustrate the difficulties
      involved in reaching a correct diagnosis. This tumour can be mistaken for a
      skeletal metastasis of an epithelial tumour.

PMID- 8559008
TI  - [Travel and pregnancy].

PMID- 8559007
TI  - [Significance of serum beta-hCG as a tumor marker for stomach carcinoma].
AB  - INTRODUCTION: Recent investigations indicate that in 50% of patients with gastric
      cancer, beta-hCG-positive cells can be found in the tumour by immunohistochemical
      investigations. The objective of this study was to investigate how often beta-hCG
      immunoreactive gastric carcinomas were accompanied by an elevation in serum beta
      hCG, that could have been used as a course control variable. METHODS: In 54
      patients with gastric carcinoma a monoclonal antibody directed against beta-hCG
      was used for immunohistochemical marking in the APAAP system. The evaluation was
      graded positive or negative. In parallel, serum beta-hCG was determined
      preoperatively using an enzyme immunoassay (MEIA). Tumour stage, grading and
      tumour localization were determinants in the evaluation. RESULTS: We found that
      41% (22 of 54) of the carcinomas induced a positive immunohistochemical response
      to beta-hCG, regardless of their location in the stomach. In relation to tumour
      stage, a positive beta-hCG immunoreactivity was apparent in 27% (6/22) of tumours
      without lymph node or distant metastases (T1-4N0M0), in 54% (7/13) of tumours
      with lymph node and without distant metastases (T1-4N > or = 1M0) and in 47%
      (9/35) of tumours with distant metastases. Poorly differentiated tumours (G3-4)
      were positive in 42% (15/36) and well-differentiated tumors (G1-2) in 39% (7/18)
      of cases. In only 1 patient was the beta-hCG level in serum elevated, however.
      CONCLUSIONS: beta-hCG-Positive gastric carcinomas are found more frequently in
      advanced tumour stages and poorly differentiated carcinomas. These carcinomas,
      however, seem not to excrete beta-hCG in sufficient amounts to produce measurable
      serum values. Therefore, beta-hCG cannot be used a prognostic factor or for
      course control. The relevance of beta-hCG expression of tumour cells to the
      patients' prognosis remains obscure.

PMID- 8559009
TI  - [At the end of the corridor to the left....].

PMID- 8559010
TI  - [New approach to health in the Federal Islamic Republic of Comoros].

PMID- 8559011
TI  - [Leptospirosis and vaccination].

PMID- 8559012
TI  - [Evaluation of Plasmodium falciparum resistance to antimalarial drugs].

PMID- 8559013
TI  - [Sickle cell anemia: how to interpret a radiological bone lesion].

PMID- 8559014
TI  - [Tropical medicine in Europe: plea for a new dream].

PMID- 8559015
TI  - [Anti-parasitic therapies: good reasons to hope....].

PMID- 8559016
TI  - [Water supply, excrement disposal and diarrheal diseases in rural zones of Ivory
      Coast].
AB  - This study was designed to determine the incidence of diarrhea over a 15 day
      period in children below 4 years living in villages in a rural area of Cote
      d'Ivoire and to identify possible correlation with water supply and excrement
      disposal. In this exhaustive cross-sectional household survey, each person caring
      for a child between the ages of 0 and 4 years was interviewed at home using an
      open, pretested survey with questions concerning diarrhea, water supply, and
      excrement disposal. Responses were authenticated by on-site observations made by
      surveyors. The study population included 1151 care providers and 1260 children
      between 0 and 4 years of age. Diarrhea had occurred in 27.7% of children within
      the 15 days prior to questioning, i.e. an annual incidence rate of 3.1 episodes
      per child after seasonal correction. Age was a risk factor for diarrhea since the
      incidence of diarrhea was inversely proportional to age. The number of episodes
      increases up to 6 months, stabilizes at a maximum of 37 to 38% until 36 months,
      and then gradually decreases to 6% between 53 and 59 months. Diarrhea was more
      common in children whose care provider was illiterate, the relative risk being
      1.22. There was also a correlation between occurrence of diarrhea and age of the
      care provider since older providers were more likely to be illiterate. Use of a
      technique to prevent water from splashing out during transport was correlated
      with diarrhea. Children whose care providers used leaves or plastic covers to
      prevent splashing during transport had more episodes of diarrhea (30%) than the
      those whose care providers did not use these techniques (23%). The place where
      stool pots were emptied was also related to diarrhea. Disposal behavior was
      strongly correlated with literacy of the care provider, with the site of disposal
      being relevant only if the provider was illiterate. In view of these findings, we
      conclude that educating women, teaching child care providers about healthy eating
      habits in children as young as 5 months, and informing families about proper
      water storage and excrement disposal would reduce the incidence of diarrheal
      disease in village children.

PMID- 8559017
TI  - [Chlamydia trachomatis in a urogenital practice: 435 specimens collected at a
      Senegalese hospital].
AB  - Between March 1993 and April 1994, tests to detect Chlamydia trachomatis were
      performed by direct immunofluorescence on genital discharges from 99 men and 336
      women at the Medical Biology Laboratory of Principal Hospital in Dakar, Senegal.
      Chlamadyial infection was demonstrated in 30 men (30.3%) and 31 women (9.2%).
      Working women who tested positive for Chlamydia trachomatis were significantly
      older than those who tested negative (p < 0.05). The opposite was true for
      working men (p < 0.05). The incidence of positive findings was significantly
      higher in students (20.5%) than in non-students (10.7%) (p < 0.05). From a
      clinical standpoint urethral discharge was noted in only 24% of infected men
      whereas vaginal discharge was present in 96% of infected women. For most infected
      women the motive for consultation was infertility. The findings of this study
      attest to the prevalence of Chlamydial infection in the population studied and
      underline the need for further study to determine its role in the etiology of
      infertility.

PMID- 8559019
TI  - [Study of a custom in Somalia: the circumcision of girls].
AB  - Female circumcision and infibulation is a common practice in parts of Africa. The
      present report describes the results of a study conducted in Somalia during
      Operation "Restore Hope". Using pre-defined questionnaire, a total of 300 women
      and 70 men were interviewed in order to evaluate the prevalence of this practice
      in Somalia, the procedures used, and the psychologic implications for the
      population. Fully 100% of the women interviewed had been circumcized and 80% had
      undergone infibulation. In most cases the procedure had been performed before the
      age of 10 years. Infection, hemorrhage and double episiotomy were reported by
      60%, 20%, and 10% of responders respectively. All but 10 responders expressed
      support for the practice and many had already had the procedure performed in
      their children. The findings of this study demonstrate that the practice remains
      widespread in Somalia where a large proportion of the population is favorable
      despite the fearful childhood memories of many women.

PMID- 8559018
TI  - [Relationship between chronic liver diseases and hepatitis C in Burundi adults].
AB  - A case/control study was conducted in Bujumbura, Burundi, from 1991 to 1992 to
      assess the relationship between chronic liver disease and hepatitis C virus
      (HCV). Patients presenting chronic liver disease (n = 80) were selected based on
      clinical, laboratory, ultrasonographic, and/or endoscopic findings. Patients with
      AIDS or hepatocellular carcinoma were excluded. Controls (n = 159) matched with
      regard to age and sex were recruited from outpatients who had blood tests at a
      liver disease clinic. Patients and controls were tested for anti-HCV antibodies
      by ELISA and LIA. Screening for hepatitis B virus (HBs antigen, anti-HBs and anti
      HBc antibodies) and human immunodeficiency virus (HIV) was achieved by ELISA with
      confirmation of HIV infection by LIA. The incidence of anti-HCV antibodies was
      significantly higher in patients (55.0%) than controls (33.3%) (p < 0.001). The
      incidence of HBs antigens was significantly higher in patients (28.8%) than
      controls (7.5%) (p < 0.0001). The incidence of anti-HIV antibodies was not
      significantly different in the two groups. Multifactorial analysis indicated that
      anti-HCV antibodies and HBs antigens were risk factors for chronic liver disease,
      but did not detected a significant interaction between these two risk factors.
      Prevention of hepatitis C and B would reduce the incidence of chronic liver
      disease but cost currently limits widespread use of this approach.

PMID- 8559020
TI  - [Heterophyiasis and diarrhea after travel: a case report of a child returning
      from a trip to Egypt].
AB  - The most frequently reported parasite-related diarrheal diseases in tropical
      travellers are amibiaisis, giardiasis, and certain types of nematoodiasis.
      Intestinal distomiasis is uncommon because the parasite is strictly limited to
      certain areas of the world. However observation is possible as is demonstrated by
      this case report involving a 3-year-old child who presented diarrhea two weeks
      after returning from a six-week stay Egypt. Heterophyes heterophyes eggs were
      identified. This small fluke has only exceptionally been reported in France where
      no indigenous case has ever been described. The present report provides an
      opportunity to review the clinical symptoms and epidemiology of this rare
      distomiasis, found only in south-east Asia and Egypt. Comparison of egg
      morphology allowed diagnosis of hysterophiasis by differentiation from smaller
      fluke species (Clonorchis and Opistorchis). The authors of this report emphasize
      that this is a rare but possible cause of diarrhea in travellers.

PMID- 8559021
TI  - [Kaposi's sarcoma in dermatology consultations at Lome, Togo].
AB  - The purpose of this retrospective study conducted in a dermatologic out patient
      clinic in Lome was to assess the epidemiologic, clinical, and prognostic profile
      of Kaposi's sarcoma in Togo during the 15 years period between 1980 and 1994.
      Only patients who had undergone serologic tests for human immunodeficiency virus
      (HIV) were included. There were 30 patients (27 men and 3 women) with a mean age
      of 35.2 years (range: 17 to 59 years). Thirteen patients were seropositive
      (epidemic Kaposi's sarcoma or EPK) and 17 were seronegative (endemic Kaposi's
      sarcoma or ENK). The mean age of patients with EPK was lower than that of
      patients with ENK (30.0 vs 42.3 years). Extensive (92.3%) and edematous (90%)
      forms and involvement of the upper extremities (66.7%), trunk (01.6%), and mucosa
      (92.3%) were characteristic clinical features of EPK while localized nodular
      forms (92.3%) were characteristic of ENK. A death was noted after 5 years of
      follow-up in the ENK group as compared to 12 deaths after a mean follow-up of
      15.95 years in the EPK group. This study illustrates the current profile of
      Kaposi's sarcoma in Black Africa where HIV infection has greatly changed clinical
      findings and prognosis.

PMID- 8559022
TI  - [Bilharziasis and human immunodeficiency virus infection in Congo].
AB  - To assess the relationship between schistosomiasis and human immunodeficiency
      virus (HIV) infection, a cross-sectional study of HIV seroprevalence was carried
      out in 1992 in a village in the Bouenza region of the Congo where there is a high
      incidence of urinary schistosomiasis. No correlation was found between eggs in
      urine and positive serology for HIV in the 895 adults examined nor between
      positive schistosome serology and positive HIV serology. The incidence of frank
      schistosome infection (eggs in urine and positive blood tests) was significantly
      lower in patients with positive HIV serology (3.5%) than in patients with
      negative HIV serology (6.7%). Similarly the mean number of eggs in urine was
      significantly lower in patients with positive HIV serology (3.6 eggs per ml) than
      in patients with negative HIV serology (26.6 eggs per ml) (p < 0.01). These
      observations suggest that HIV infection limits schistosome development and
      decreases antibody production. Further study will be needed to confirm these
      findings.

PMID- 8559023
TI  - [Autopsy findings in 70 AIDS patients who died in a department of pneumology in
      Ivory Coast: impact of tuberculosis].
AB  - Based on autopsy findings in 70 patients infected by human immunodeficiency virus
      (HIV) who died in the Pulmonology Department of the Treichville University
      Hospital Center in Abidjan, Ivory Coast. the authors assess the incidence of
      tuberculosis as the cause of death and analyze the clinical, bacteriologic, and
      histologic features of the disease. in this population. Pulmonary tuberculosis
      was the first cause of death in this series accounting for 31 cases (44.2%). In
      12 cases (38.7%), microscopic identification failed during hospitalization and
      the disease had been misdiagnosed as common bacterial pneumonia. In 29 cases
      (93.5%) pulmonary tuberculosis was associated with abdominal involvement. In 17
      cases (54.8%) involvement of more than two organs was observed. Of the 60
      abdominal sites detected during the autopsy of the 31 patients with pulmonary
      tuberculosis, there were 19 (31.3%) in lymph nodes, 18 (30%) in the liver, 14
      (23.3%) in the spleen, and 9 (14.9%) in the kidneys. Histologic features were
      remarkable by the absence of typical tuberculous granulomas. The findings of this
      study confirm the high incidence of disseminated tuberculosis in patient infected
      by HIV as noted in a number of previous studies.

PMID- 8559024
TI  - [Sensitivity of Acinetobacter baumannii to antibiotics and disinfectants used in
      a Tunisian hospital milieu].
AB  - Seventy-nine strains of Acinetobacter baumannii isolated from pathologic products
      obtained mainly from surgical and intensive care units at the Rabta Hospital in
      Tunisia were studied. The sensitivity of these bacteria to the antibiotics used
      singly or in combination was tested in order to determine the most effective
      agents. Sensitivity to the disinfectants routinely used in our hospital was also
      studied using the "dilution-neutralisation" method according to "AFNOR" norms in
      order to identify the product with the most powerful preventive effect for
      Acinetobacter baumannii infection. The bacteria tested were resistant to all
      antibiotics except imipernem, colistin, and some aminoglycosides. A combination
      of imipenem-amikacin was effective against all strains. Best disinfection was
      obtained after 5 minutes of bacterial contact with aldehyde, phenol and
      amphotere.

PMID- 8559025
TI  - [Porocephalosis, a little known parasitosis, literature review and a Congolese
      case report].
AB  - The authors describe another case of symptomatic porocephalosis in a 59-year-old
      man from the Congo and review recent epidemiologic, clinical, and laboratory data
      from the literature concerning pentastomiasis in man. There are a variety of
      modes of transmission to man, parasitic dead end, and sites of infection. A
      perusal of symptomatic cases reported since 1970 confirms that complications are
      mainly associated with uncalcified nymphal forms. This poses a diagnostic problem
      since clinical and laboratory findings associated with young forms in non
      specific. When feasible, surgical resection of infested tissue allows diagnosis
      and treatment. Many questions remain unanswered concerning the incidence of
      pentastomiasis in endemic areas, its physiopathology, and its relationship with
      cirrhosis and liver cancer in the tropics. New diagnostic techniques (serologic
      tests, ultrasonography, CT-scan) may help to resolve these issues.

PMID- 8559026
TI  - [Noma or cancrum oris: etiopathogenic and nosologic aspects].
AB  - Noma is a gangrenous disease that usually begins in the mouth and is
      characterized by rapid necrotizing destruction of soft tissue and underlying
      bone. The disease, which is associated with a strong putrid odor suggestive of
      mixed bacterial infection, develops only in predisposed persons, especially
      children whose natural defenses have been weakened by poor socio-economic living
      conditions. However a few atypical cases have recently been reported in adults in
      whom the main risk factor seemed to be immunodepression. The increasing number of
      wars in the Third World and the AIDS epidemic raise the likelihood that the
      number of cases of this disease will rise sharply particularly since the
      incidence has been grossly underestimated for many years. It now seems clear that
      a combination of local and systemic risk factors are implicated in the
      etiopathogenesis of noma with the common denominator being a weakened immune
      system. This would account for the fulminating course of the infectious process
      due to one or more opportunistic microbial or cytopathogenic agents or even to a
      still undetermined immunopathologic reaction that lead to massive tissue
      destruction. Poor understanding of the etiopathogenesis of noma is a major factor
      perpetuating the nosologic problems posed by this disease. Some authors add to
      the confusion by including a range of gangrenous diseases under the heading of
      noma. It is important that the term noma be applied only to necrotizing processes
      that begin in the mouth and present the characteristic features and course.

PMID- 8559027
TI  - [Vietnam: appropriate management of a pediatric hospital in the context of
      limited resources].
AB  - To cope with problems arising from limited economic resources, the pediatric
      hospital of Ho Chi Minh City, Vietnam, integrated several primary health care
      concepts into its overall policy: designation of priority diseases, adaptation of
      therapeutic modalities, decentralisation, and community funding. These concepts
      have been in use since 1988. Five diseases were designated for priority, i.e.
      diarrhea, acute pulmonary infection, dengue fever (DF), malaria, and routine
      pediatric emergencies, malnutrition. Training courses focusing on these diseases
      have been organized for hospital staff and health care assistants and education
      programs have been offered to the families of patients. Outpatient treatment is
      encouraged to lower the number of unnecessary hospitalizations and use of simple,
      cost-effective therapies has been developed for priority diseases. Responsibility
      has been delegated to department heads. Treatment is provided at no cost to the
      poorest but a small fee is requested from others and funding is also obtained
      from local authorities and non-governmental organizations. In five years, these
      concepts have achieved a 40% reduction in overall mortality. Funding from non
      governmental organizations has been allocated to training and research programs
      designed to respond to specific community needs. This experience shows that
      reducing mortality does not depend only on budgetary increases but also to a
      great extent on rational spending and managing available resources. These can be
      effective in any developing countries that cannot increase budgetary spending.

PMID- 8559028
TI  - [Niger: nutritional recuperation and education in a sub-Saharan urban area].
AB  - Located in Niamey, capital of Niger, a Sub-Saharian country where the rate of
      acute malnutrition in children is estimated at 16.8 percent, the National Armed
      Forces Center for Nutritional Rehabilitation and Education has been expanding its
      activities since 1986. The center offers curative and educational services to the
      children of military personnel and the population in neighboring districts. These
      services are regularly scheduled two and a half or three hours each morning five
      days a week. In 1990 our center received 115 malnourished children detected
      either during consultations or infant weighing sessions. Twenty-seven presented
      moderate protein-caloric malnutrition and 28 serious malnutrition. Medium age at
      admission was 11 months 16 days and medium length of stay was 9.5 days. Long-term
      recovery was confirmed in 30.5% while 69.5% were lost from follow-up. Keeping a
      healthbook throughout the weight control period, enforcing coercive measures for
      military families, organizing a permanent campaign to maintain awareness of
      nutritional problems, prolonging opening hours to improve access to the center,
      and above all improving the level of women's education are necessary to improve
      these results. Primary prevention requires better family planning with a longer
      interval between births.

PMID- 8559029
TI  - [In vivo evaluation of Plasmodium falciparum sensitivity to chloroquine in
      Moundou, Chad].

PMID- 8559030
TI  - [Gallbladder schistosomiasis haematobium. A case report].

PMID- 8559031
TI  - [The quantitative buffy coat technique in detecting trypanosomes].

PMID- 8559032
TI  - [Seroprevalence of human toxocariasis in Wallis].

PMID- 8559033
TI  - [Darier-Ferrand dermatofibrosarcoma: six case reports].

PMID- 8559034
TI  - [Reflections on dental caries in schoolchildren in Lome].

PMID- 8559035
TI  - Purification and characterization of a CHO cell-elongating toxin produced by
      Aeromonas hydrophila.
AB  - A Chinese hamster ovary (CHO) cell-elongating toxin produced by Aeromonas
      hydrophila was purified from cell-free supernatant fluids by ammonium sulfate
      precipitation and fast protein liquid chromatography. The purified toxin had an
      isolelectric point (pl) of 3.7 and a molecular weight of 70,000 in a single band
      on isoelectric focusing (IEF) gels and SDS-PAGE gels, respectively. The N
      terminal sequence, amino acids 1-20, and the amino acid content were determined
      from Western blots of the 70 kDa band. No homology with any known microbial toxin
      was found. CHO cell activity was not neutralized by antiserum to cholera toxin
      (anti-CT), and the toxin did not react with anti-CT on Western blots. The toxin
      did not increase cyclic AMP, cyclic GMP, or prostaglandin E2 levels in CHO cells.
      No cytotoxic activity was observed. Intragastric administration of purified toxin
      (5 x 10(4) and 5 x 10(8) CHO cell units) induced intestinal fluid accumulation in
      infant mice. These results suggest that this toxin may be a novel cytotonic toxin
      distinct from previously described toxins produced by A. hydrophila or A. sobria.

PMID- 8559036
TI  - Thymine auxotrophy as an attenuating marker in Vibrio cholerae.
AB  - Vibrio cholerae CVD102 is a thymine-dependent auxotroph of CVD101, a cholera
      toxin A-B+ candidate live oral cholera vaccine. Previous clinical experience with
      these strains suggested that, by restricting intestinal growth, thymine
      auxotrophy is attenuating for V. cholerae. Studies in the infant mouse cholera
      model cast doubt upon this conclusion however. Stable thyA mutants selected from
      each of three pathogenic strains showed unimpaired gut colonization in mixed
      infection competition experiments. Similar results were obtained using thyA
      mutants selected from two atoxigenic strains, including CVD101. Further studies
      with CVD102 showed that the reduced colonization potential of this strain could
      not be compensated by the provision of a functional thyA+ gene in trans. CVD102
      shows reduced synthesis of toxin-coregulated pili (TCP) during in vitro growth,
      suggesting the presence of a second, undefined mutation in this strain. Given the
      critical role of TCP in intestinal colonization, it seems probable that this
      previously unrecognized mutation is responsible for the poor in vivo performance
      of CVD102.

PMID- 8559037
TI  - Ex vivo induction of TNF-alpha and IL-6 mRNA in bovine whole blood by
      Mycobacterium paratuberculosis and mycobacterial cell wall components.
AB  - Johne's disease is a chronic enteritis of cattle and other ruminant species that
      is of worldwide economic importance. The cytokines tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-6 (IL-6) have been associated with granuloma
      formation and wasting in other disease syndromes. The potential role of these
      cytokines in the development and progression of Johne's disease has not been
      investigated. Using reverse transcriptase polymerase chain reaction (RT-PCR) and
      specific bovine oligonucleotide cytokine primers and probes for bovine TNF-alpha
      and IL-6, we examined the ex vivo expression of mRNA for these inflammatory
      cytokines in whole blood from healthy cattle. Cytokine mRNA levels increased
      after a brief incubation of bovine whole blood with Mycobacterium
      paratuberculosis or its lipoarabinomannan (LAM). Muramyl dipeptide (MDP) and
      Escherichia coli LPS also stimulated TNF-alpha and IL-6 mRNA expression. Several
      strains of M. paratuberculosis were tested and found to have similar abilities to
      stimulate TNF-alpha and IL-6 mRNA expression. Several strains of the closely
      related Mycobacterium avium, and the unrelated saprophyte, Mycobacterium phlei,
      had somewhat less ability to stimulate TNF-alpha and IL-6 mRNA expression.

PMID- 8559038
TI  - Specificity of the immune response to Haemophilus ducreyi.
AB  - The specificity of the antibody response to Haemophilus ducreyi in sera from
      patients attending a sexually transmitted disease clinic in South Africa has been
      studied using immunoblotting. Patients with chancroid were shown to have higher
      levels of IgG (mean 0.74, SD 0.34) to H. ducreyi than those with no history of
      chancroid (mean 0.34, SD 0.19). The pattern of the antibody specificity was
      highly variable between patients with culture proven chancroid but there was no
      observed strain specificity. In comparison, the patterns obtained using sera from
      patients without known exposure to H. ducreyi showed less variation between
      patients and were of less intensity at the dilution used. Sera from patients with
      chancroid recognised epitopes on proteins that varied in molecular weight between
      strains, particularly of 60-66kDa (10 of 36 patients) and 25-27kDa (8 of 36
      patients). In addition epitopes were recognised on the GroEL and/or DnaK heat
      shock proteins in 13 of 36 sera tested. There was no apparent change in the
      epitopes recognised on proteins between the homologous and heterologous strains.
      Patterns of antibody specificity in sequential sera only varied in one of six
      patients tested.

PMID- 8559039
TI  - Pathogenesis studies on Vibrio alginolyticus in the grouper, Epinephelus
      malabaricus, Bloch et Schneider.
AB  - A pathogenic vibrio, strain S3y was isolated from an outbreak of vibriosis in
      grouper (Epinephelus malabaricus) fry in Kaohsiung, Southern Taiwan in November
      1991. It was identified as Vibrio alginolyticus on the basis of a number of
      biochemical tests. The bacterium was therefore identified as Vibrio, a Gram
      negative, straight rod, motile, oxidase and catalase positive, swarming on TSA
      plate, fermentative and produced yellow colonies on TCBS agar. It did not utilise
      sodium citrate, but it was gelatinase positive and sensitive to the vibriostatic
      agent, 0/129. It could grow on TSA with up to 11% NaCl. Its G+C ratio was 47%.
      The minimum lethal dose of strain S3y was 500 cfu/g fish body weight in the
      grouper (Epinephelus malabaricus). The same bacterial species could be reisolated
      from the kidney of moribund fish following bacterial challenge. The extracellular
      products (ECP) of S3y were lethal to fish with a minimum lethal dose of 0.52
      microgram/g fish body weight. A 34 kDa protease was purified from the ECP of S3y
      and demonstrated to be a toxin by intraperitoneal injection in the grouper. The
      minimum lethal dose of the purified protease was 0.17 microgram/g fish body
      weight. Intraperitoneal injection of the bacteria, ECP or the 34 kDa protease all
      caused slight exophthalmia with corneal opaqueness in moribund and dead fish. The
      results suggested that the 34 kDa protease might play an important role in the
      pathology of vibriosis caused by this bacterium.

PMID- 8559040
TI  - Opsonization of Staphylococcus aureus with a fibronectin-binding protein
      antiserum induces protection in mice.
AB  - The virulence of Staphylococcus aureus opsonized with an antiserum raised against
      a recombinant fibronectin-binding protein (FnBP) was compared with homologous,
      non-opsonized bacteria (treated with pre-immune serum) in a mouse mastitis model.
      Virulence was evaluated comparing the number of bacteria removed from the
      infected mammary glands and according to the type of lesions produced. The
      average number of bacteria recovered from the mammary glands inoculated with S.
      aureus opsonized with FnBP-antiserum was significantly lower (up to 10(7) cfu/ml)
      than the average number of bacteria recovered after inoculation with non
      opsonized bacteria (up to 10(10) cfu/ml). Gross examination of infected mammary
      glands showed that 65% of glands infected with opsonized bacteria developed low
      grade/or had no pathological changes, and 35% developed severe mastitis whereas,
      75% of glands inoculated with non-opsonized bacteria developed severe mastitis
      and 25% low grade mastitis or had no pathological changes. According to the
      histopathological examination eight out of 10 glands inoculated with opsonized
      bacteria produced disseminated focal necrosis or had no pathological changes and
      two glands produced non reactive necrotic lesions. In contrast, only three out of
      10 glands inoculated with non-opsonized homologous bacteria developed
      disseminated focal necrosis and had no pathological changes while seven glands
      developed total necrosis.

PMID- 8559041
TI  - Persistent Yersinia enterocolitica infection in three rat strains.
AB  - Yersinia enterocolitica may persist for prolonged periods of time in humans
      sometimes resulting in the development of reactive arthritis. To elucidate
      factors predisposing for persistence we developed animal models. In Lewis and
      Fischer rats, viable bacteria could be demonstrated for prolonged time and
      abscesses could be found in the liver, spleen and lungs. Splenic abscesses were
      observed for more than 20 weeks. Yersinia enterocolitica persisted in Lewis and
      Fischer rats, but only Lewis rats developed reactive arthritis. In Brown Norway
      rats abscesses developed early during infection but in contrast to the other
      strains disappeared after 3 weeks. Culture of homogenized abscess-containing
      tissue of all three rat strains yielded Yersiniae. Immunofluorescence studies of
      the abscesses showed diffuse staining inside the abscesses only, indicating the
      presence of Yersinia enterocolitica antigen. Brown Norway rats, in contrast to
      Lewis and Fischer rats, developed a different serological reaction pattern
      against Yersinia enterocolitica antigens and this correlated with the
      disappearance of the abscesses.

PMID- 8559042
TI  - Fibronectin binding by Streptococcus milleri group strains and partial
      characterisation of the fibronectin receptor of Streptococcus anginosus F4.
AB  - The Streptococcus milleri group were shown to bind fibronectin (Fn) to their cell
      surface and this binding increased the adhesion of cells to hydroxyapatite. The
      binding of Fn to Streptococcus anginosus F4 was studied in more detail. Fn
      binding to bacterial cells increased the association of the bacteria with the
      polymorphonuclear leukocytes obtained from the peritoneal cavity of rats but did
      not increase killing of the bacteria. The cell-surface receptor was a protein of
      M(r) 14,000 which was released from cells after mutanolysin digestion. The
      binding was specific, with cells having a maximum number of binding sites per
      cell of 770. Electron microscopy, using gold-labelled Fn, localised the receptor
      to areas between daughter cells.

PMID- 8559043
TI  - Binding specificity for four monoclonal antibodies recognizing terminal Gal alpha
      1-->4Gal residues in Haemophilus influenzae lipopolysaccharide.
AB  - Four murine monoclonal antibodies (MAbs) reactive with the outer-core region of
      the lipopolysaccharide (LPS) from Haemophilus influenzae were generated after
      immunization with azide-killed H. influenzae RM.7004 AH1-2 and their epitope
      specificities studied. The monoclonal antibodies: MAHI 6 (IgM), MAHI 5 (IgG2a),
      MAHI 8 (IgG3), and MAHI 11 (IgG2b) bound to synthetic glycoconjugates or
      glycolipids with terminal galabiosyl (Gal alpha 1-->4Gal beta 1-) or
      globotriaosyl (Gal alpha 1-->4Gal beta 1 1-->4GLc) residues as evaluated in
      enzyme immunoassays (EIA). Glycoconjugates or glycolipids with internally placed
      galabiose elements were not active, indicating selectively of the MAbs for
      recognition of the epitope. Nine LPSs from H. influenzae inhibited the binding of
      the four MAbs. The presence of the galabiosyl disaccharide element in these nine
      LPSs was evidence by the binding of 125I-labeled Shiga toxin isolated from the
      bacterium Shigella dysenteriae type 1, reported to have as receptor the Gal alpha
      1-->4Gal beta disaccharide (Lindberg et al., J Biol Chem, 1987, 262: 1779-85).
      Structural studies of these H. influenzae LPSs were also in accord with the
      presence of the galabiosyl disaccharide, in addition 1H-NMR spectroscopy showed
      the presence of O-acetyl groups in the RM.7004 AH1-2 LPS. However, differential
      binding specificities of the MAbs to modified RM.7004 AH1-2 LPSs were observed.
      MAHI 6 and MAHI 11 bound equally well to LPS, polysaccharides obtained after mild
      acidic treatment, and dephosphorylated LPS samples as shown in inhibition EIA. In
      contrast, both dephosphorylated LPS samples and polysaccharides were poorer
      inhibitors of the binding of MAHI 5 and MAHI 8 to native RM.7004 AH1-2 LPS.
      Neither the de-O-acylated nor the de-O,N-acylated LPSs were effective inhibitors
      of any of the four MAbs. These results suggest that the MAbs recognition involves
      Gal alpha 1-->4Gal and O-acetyl and other saccharide residue(s) from the
      oligosaccharide moiety of the LPS. The epitopes are also expressed and accessible
      to recognition in clinical isolates coming from different sources of Neisseria
      spp., Haemophilus spp., and Moraxella catarrhalis, but not in Bordetella spp.,
      Aeromonas spp. or Enterobacteriaceae as evaluated by whole-bacteria EIA and
      colony-dot-immunoblotting.

PMID- 8559044
TI  - Short-chain lipopolysaccharide mutants of serogroup B Neisseria meningitidis of
      potential value for production of outer membrane vesicle vaccines.
AB  - Four lipopolysaccharide (LPS) mutants (Mu-1 to Mu-4) were isolated after exposing
      Neisseria meningitidis strain 44/76 to pyocins from Pseudomonas aeruginosa.
      Parent strain LPS contained one major SDS-PAGE band expressing the immunotype
      determinants of L3, L3,7 and L3,7,9 and a minor band of higher mobility
      expressing the immunotype determinants of L8, L8a, L1,8,10 and L11. Each mutant
      LPS appeared as one SDS-PAGE band of higher mobility than the bands of the parent
      strain. None of these LPSs expressed the immunotype determinants of the parent
      strain, except Mu-4 LPS which reacted with the L11-specific MAb 4C4. Strain 44/76
      LPS was found to contain galactose (Gal), glucose (Glc), heptose (Hep),
      glucosamine (GlcN), and 2-keto-3-deoxy-octulosonic acid (Kdo) in the molar ratios
      of 1.9:1.3:1.7:3.5:2.1. The corresponding ratios of the mutants were: Mu-4,
      0:1.7:1.7:2.8:2.0; Mu-3, 0:0:1.7:2.4:1.6; Mu-2, 0:0:2.1:1.8:2.0, Mu-1,
      0:0:1.8:1.9. Thus, all mutant LPSs lacked Gal and possessed less GlcN as compared
      to strain 44/76 LPS. Consequently, these mutants do not express the lacto-N-neo
      tetraose (Gal1-4GlcN1-3Gal1-4Glc) commonly found as a part of meningococcal LPS
      and also on structures of human erythrocytes. These LPS mutants will be
      considered for use in production of OMV vaccines without host-like antigens,
      which might favour induction of antibodies to more conserved epitopes of
      meningococcal LPS.

PMID- 8559045
TI  - Apoptosis as a cause of death in chicken embryos inoculated with Newcastle
      disease virus.
AB  - Eleven-day-old chicken embryos were inoculated by the allantoic route with the GB
      strain of Newcastle disease virus (NDV). At 0, 24, 36 and 42 h post-inoculation
      (p.i.), the brain and heart tissues were harvested for DNA extraction, and the
      thymus and the brain were fixed and processed for light and electron microscopy.
      At 42 h p.i., most of the embryos had died; however, no histopathological changes
      could be seen in the embryos at any stage of infection. DNA extracted from the
      brain cells started showing fragmentation at 24 h p.i., and from the heart muscle
      cells at 36 h p.i. Electron microscopy of the brain and thymus showed
      condensation of the nuclear chromatin, apoptotic bodies, various forms of
      crescent formation and some evidence of necrosis. Fragmentation of cellular DNA,
      crescent formation and apoptotic bodies are the typical signs of cells undergoing
      apoptosis. We suggest that apoptosis of the heart and brain is probably a cause
      of death of chicken embryos in acute Newcastle disease infection.

PMID- 8559046
TI  - Tumor necrosis factor as a mediator of inflammation in influenza A viral
      pneumonia.
AB  - The role of tumor necrosis factor alpha (TNF alpha) in the pathogenesis of
      influenza A viral pneumonia was examined. CD-1 male mice were challenged
      intranasally with influenza A virus A/PR/8/34 (H1N1) and administered rabbit anti
      mouse TNF alpha-specific-neutralizing antibodies intraperitoneally. The effect of
      treatment on virus titer, TNF alpha levels, morbidity, mortality, and on
      pathologic lung lesions were compared with sham-treated controls. The severity of
      gross and histologic lung lesions positively correlated with the peak
      bronchoalveolar TNF alpha levels and was ameliorated with anti-TNF alpha
      treatment. Survivorship was prolonged in mice given a lethal dose of virus by
      treatment with TNF-alpha neutralizing antibodies. Reduction of TNF alpha levels
      by treatment with TNF alpha-antibodies did not affect virus titers in the lung.
      These results suggest that TNF alpha is a mediator of pulmonary inflammation
      during influenza A viral pneumonia, but may not play a significant anti-viral
      role in influenza pneumonia.

PMID- 8559047
TI  - Increased oral virulence of Escherichia coli expressing a variant Shiga-like
      toxin type II operon is associated with both A subunit residues Met4 and Gly102.
AB  - We have previously demonstrated that Escherichia coli DH5 alpha clones expressing
      closely-related Shiga-like toxin type II operons (designated SLT-II/OX3b and SLT
      II/O48) had similar cytotoxicity for Vero cells, but differed in oral virulence
      for streptomycin-treated mice. Studies with chimeric toxin operons indicated that
      increased virulence was associated with the A subunit of SLT-II/OX3b, which
      differs from that of SLT-II/O48 by two amino acids (at positions 4 and 102). In
      the present study, we have constructed a series of additional chimeric
      derivatives of the SLT-II/OX3b and SLT-II/O48 operons and assessed the effect of
      single A subunit amino acid substitutions on oral virulence. Maximal virulence,
      as judged by median survival time after oral challenge, was associated only with
      the combination of Met4 and Gly102, as found in the A subunit of SLT-II/OX3b.

PMID- 8559048
TI  - [Social-occupational risk factors for fetal growth retardation and preterm birth.
      I. Role of occupational and non-occupational work].
AB  - Clinical and control examinations were performed in order to assess the effect of
      certain demographic, social and occupational factors on a relative risk for fetus
      hypotrophia and preterm birth. Two groups of cases were distinguished: mothers of
      hypotrophic children (72 women) and mothers of eutrophic premature babies (41
      women). The control group was composed of women who had given birth to eutrophic
      babies (438 persons). An analysis of individual variables indicated the following
      risk factors for preterm birth: mother's age over 35 years, unmarried status of
      mothers, a low level of education; while unmarried status increased the risk for
      fetus hypotrophia. Only a half of women under study worked when pregnant, and no
      relationship between working during pregnancy and increased risk for the
      pathologies discussed, were found. An aggravated risk for preterm birth in women
      overloaded with housekeeping duties was noted. This observation applied, in
      particular, to women who had not been working occupationally during pregnancy.
      Bearing in mind a multifactorial etiology of fetus hypotrophia and preterm birth,
      in the authors' opinion it would be useful to analyse an unrelated effect of
      individual risk factors with concomitant control of confounding factors.

PMID- 8559049
TI  - [Social-occupational risk factors for fetal growth retardation and preterm birth.
      II. An analysis of the independent effect of variables under study].
AB  - In the study covering 551 female inhabitants of Lodz, a model for clinical and
      control examinations was used in order to identify risk factors (estimated by
      means of odds ratio) for fetus hypotrophia and preterm birth. Logistic regression
      was employed to determine independent variables and those contributing directly
      to the occurrence of both pathologies. The following risk factors for preterm
      birth and fetus hypotrophia were identified: smoking during pregnancy, bleeding
      in more than one trimester of pregnancy and low weight gain by mothers during
      pregnancy. Late reporting to a doctor, uterus cervical insufficiency, recent loss
      of the job, excessive responsibility for the management of household affairs and
      premature baby or a baby with low birth weight as an outcome of the previous
      pregnancy were proved to be specific risk factors responsible for preterm birth,
      while marital status, namely single young mothers, and short stature of mothers
      were responsible for fetus hypotrophia. The results obtained did not provide the
      basis for drawing a conclusion that work during pregnancy exerted an adverse
      effects and contributed to the magnitude of the analysed obstetric pathologies.
      Nevertheless, risk factors identified should be taken into account in the
      planning of mother and child care. The authors stress the need for taking further
      steps to eliminate, wherever possible, the aforesaid risk factors.

PMID- 8559050
TI  - [Neurologic and neurophysiologic evaluation of workers occupationally exposed to
      mixed organic solvents. Preliminary study].
AB  - The study covered 72 persons (39 females and 33 males), engaged in the production
      of dyes and varnishes, and exposed to mixtures of organic solvents which contain
      benzene C-9 and C-10 alkyl derivatives. For females--length of employment
      accounted for mean = 15.9 years and cumulative exposure index for mean = 12.11,
      and for males - mean = 16.4 years and mean = 12.17, respectively. The study
      results applying to the group exposed were compared with the results of the
      controls matched according to gender, age and work shifts. Clinical examination
      indicated that among complaints the following manifestations predominated:
      headache, dizziness, increased emotional excitability, memory and concentration
      disturbances, hypersomnia during a day and mood instability. Subjective symptoms
      were more frequently observed in females. Neurological examination revealed no
      organic changes neither in the central nor in the peripheral nervous system.
      Certain anomalies were noted in EEG and visual evoked potential (VEP)
      examinations which may indicate pre-clinical changes in the nervous system.

PMID- 8559051
TI  - [Mortality of workers in the dye industry. I. Analysis of general mortality].
AB  - A mortality study was carried out among workers employed in a plant producing
      different kinds of dyes using benzidine. The cohort comprised 8,523 males and
      2,006 females whose vital status was recorded between Jan 1, 1945 and Dec 31,
      1991. They had worked in this plant for, at least, 3 months between Jan 1, 1945
      and Dec 31, 1974. The cohort was divided into 4 subcohorts: I. those exposed only
      to benzidine; II. those exposed to benzidine and to other occupational hazards;
      III. those involved directly in the dyes production but not exposed to benzidine,
      and IV. those not involved directly in the dye production-mainly administrative
      staff. Death risk was estimated on the basis of standardized mortality ratio
      (SMR), determined by means of the person-years method. The general population of
      Poland was taken as a reference group. The observed number of deaths in the
      cohort and each subcohort was compared with expected deaths. The comparison was
      based on the national rates by adjustment for age, gender and calendar time. An
      excessive mortality due to mental disorders (SMR = 2.37) was found in the male
      cohort, and due to atherosclerosis in both cohorts--male (SMR = 1.25) and female
      (SMR = 1.37). An analysis of mortality in subcohorts showed similar but not the
      same relationship. Mortality because of malignant neoplasms will be presented in
      the next paper.

PMID- 8559052
TI  - [Mortality among the dye industry workers. II. An analysis of malignant neoplasm
      mortality].
AB  - A mortality study was carried out among workers employed in a plant producing
      different kinds of dyes, including benzidine. The cohort comprised 8,523 males
      and 2,006 females whose vital status was recorded between Jan 1, 1945 and Dec.
      31, 1991. They had worked in this plant for, at least, 3 months between Jan. 1,
      1945 and Dec 31, 1974. The cohort was divided into 4 subcohorts: I. those exposed
      only to benzidine: II. those exposed to benzidine and other occupational hazards;
      III. those involved directly in the dye production but not exposed to benzidine,
      and IV. those not involved directly in the dye production-mainly administrative
      staff. Death risk was estimated on the basis of standardized mortality ratio
      (SMR) determined by means of the person-years method. The general population of
      Poland was taken as a reference group. The observed number of deaths in the
      cohort and each subcohort was compared with expected deaths. The comparison was
      based on national rates by adjustment for age, gender and calendar time.
      Significant excessive mortality due to cancer of urinary bladder was observed in
      the male subcohort I (SMR = 14.69), II (SMR = 16.34) and III (SMR = 3.17); due to
      malignant neoplasm of pancreas in the male subcohort II (SMR = 3.26); due to
      malignant neoplasm of testis in the male subcohort III (SMR = 3.17); due to
      malignant neoplasm of pancreas in the male subcohort II (SMR = 3.26); due to
      malignant neoplasm of testis in the male subcohort III (SMR = 3.23). Significant
      excessive mortality due to malignant neoplasm of liver and intrahepatic bile
      ducts was found in the female subcohort IV (SMR = = 2.36).

PMID- 8559053
TI  - [The effect of exogenous iron on levels of adenosinetriphosphate and 2,3
      diphosphoglycerate in erythrocytes of men during extreme physical exertion].
AB  - Nine men were examined during a three-week training requiring much physical
      effort. They were given nutrient, "LIVEX", enriched with iron. Hematological
      parameters as well as concentration of erythrocyte ATP and 2,3-DPG were
      determined before and after the experiment. Hematological parameters were
      determined using standard methods while Boehringer's test (Germany) was used for
      determining ATP and 2,3-DPG. The level of reticular cells was statistically
      higher after the experiment, and the increase in ATP and 2,3-DPG concentration
      was insignificant. A positive adaptation of energy metabolism after exogenous
      iron administration during physical effort was discussed.

PMID- 8559054
TI  - [Emission of electromagnetic radiation from selected computer monitors].
AB  - The emission of electromagnetic fields from computer monitors was analysed. The
      data were compared with the permissible exposure level. EM radiation of chromatic
      monitors is higher than that of monochromatic ones. The radiation of magnetic
      fraction is insignificant. Both electric and magnetic fractions of EM radiation,
      50 cm away from the monitor, are very low and do not exceed permissible values.
      It was observed that screen filters were effective in suppressing EM emission
      only at a short (up to 30 cm) distance from the monitor. At a distance of 50 cm
      they proved to be ineffective. Metallic-net filters were more effective than
      glass filters in suppressing EM radiation. It seems that EM fields generated by
      computer monitors are not harmful to computer operators if the distance is kept
      in safe limits.

PMID- 8559055
TI  - [Classification of neuroses in the practice of occupational health physicians].
AB  - The author discussed current opinions on classification of neuroses. She stressed
      the diversified and complicated terminology which has been developed in this
      regard for the requirements of psychiatrists and statistics. The description of
      individual types of neuroses, useful for occupational health service physicians
      and based on a concise definition of major symptoms, is proposed.

PMID- 8559056
TI  - [Glutathione S-transferase as a metabolic biomarker for predisposition to lung
      neoplasms induced by chemical carcinogens].
AB  - In the case of lung cancer induced by chemical carcinogens, cellular processes of
      metabolic activation and deactivation of these substances play a particular role.
      The involvement of glutathione--S-transferase in the process of deactivation of
      active metabolites draws special attention. Cellular activity of these enzymes is
      a significant factor which can define individual susceptibility to carcinogenic
      effect of occupational and environmental carcinogens. Glutathione--S-transferase
      catalyses the reaction of binding glutathione with a great number of
      pharmacologically active substances, including also those with genotoxic
      properties. These reactions protect cells against toxic and genotoxic effect of
      exo- and endogenous substances. They prevent among others, from producing adducts
      by genotoxic substances with macromolecules. Some of glutathione--S-transferases
      (the so-called ligands) act as proteins which bind and transport organic ligands
      in cells (bilirubin, steroid metabolites, bile acids). To date studies have not
      confirmed uni-vocally that low activity of glutathione--S-transferases be one of
      the reasons for an increased incidence of lung cancer. Observations of persons
      with phenotype of a low activity of glutathione--S-transferase (GSTM1-0) have
      indicated that the incidence of lung cancer is significantly higher among them
      than in persons with phenotype of normal activity of this enzyme. These
      observations, however, have not been confirmed by an analysis of relationship
      between the incidence of lung cancer and the genotype of low and normal activity
      of glutathione--S-transferase.

PMID- 8559057
TI  - [Indications for psychological examination in diagnosis, certification and
      prevention of occupational diseases].
AB  - The work is based on the author's clinical experience gained due to her
      responsibilities as a consultant in the Department of Occupational Diseases,
      Nofer Institute of Occupational Medicine, Lodz, as well as on the literature
      dealing with the effect of some chemical and physical occupational hazards on the
      central nervous system. The author points out that psychological examinations
      play a significant role in diagnosis and prevention of occupational disease. She
      suggests that workers should be subjected to periodical psychological
      examinations during the whole period of employment. Particular indications for
      these examinations are also discussed.

PMID- 8559058
TI  - [Computer systems in medical practice. I. The aims, difficulties and
      implementation of computerization in health care organizations].
AB  - Several phenomena accompanying the implementation of computer systems in polish
      health care are discussed. The initiatives of managers of health care
      organizations or individual hospitals, are directed toward the software
      supporting their financial and administration activities. On the other hand, the
      Ministry of Health initiatives deals mainly with registration of manpower
      (doctors, nurses, etc.), and registration of equipment of health care
      organizations. Several computer programs elaborated by the polish authors are
      adjusted to the needs and abilities of health care organizations, hospital and
      private practices of individual doctors. However, the possibilities of data
      exchange between different computer software systems are rather limited.
      Implementation of computer systems are accompanied by the resistance resulting
      from the fears personnel which uses computers in the health care organizations.
      The effectiveness of computer systems implementation depends mainly on the user's
      ability to define precisely his needs, and on approval the computer system by the
      personnel.

PMID- 8559059
TI  - RNA capping enzyme and DNA ligase: a superfamily of covalent nucleotidyl
      transferases.
AB  - mRNA capping entails GMP transfer from GTP to a 5' diphosphate RNA end to form
      the structure G(5')ppp(5')N. A similar reaction involving AMP transfer to the 5'
      monophosphate end of DNA or RNA occurs during strand joining by polynucleotide
      ligases. In both cases, nucleotidyl transfer occurs through a covalent lysyl-NMP
      intermediate. Sequence conservation among capping enzymes and ATP-dependent
      ligases in the vicinity of the active site lysine (KxDG) and at five other co
      linear motifs suggests a common structural basis for covalent catalysis.
      Mutational studies support this view. We propose that the cellular and DNA virus
      capping enzymes and ATP-dependent ligases constitute a protein superfamily
      evolved from a common ancestral enzyme. Within this superfamily, the cellular
      capping enzymes display more extensive similarity to the ligases than they do to
      the poxvirus capping enzymes. Recent studies suggest that eukaryotic RNA viruses
      have evolved alternative pathways of cap metabolism catalysed by structurally
      unrelated enzymes that nonetheless employ a phosphoramidate intermediate.
      Comparative analysis of these enzymes, particularly at the structural level,
      should illuminate the shared reaction mechanism while clarifying the basis for
      nucleotide specificity and end recognition. The capping enzymes merit close
      attention as potential targets for antiviral therapy.

PMID- 8559060
TI  - RNase P--a 'Scarlet Pimpernel'.
AB  - RNase P is responsible for the maturation of the 5'-termini of tRNA molecules in
      all cells studied to date. This ribonucleoprotein has to recognize and identify
      its cleavage site on a large number of different precursors. This review covers
      what is currently known about the function of the catalytic subunit of
      Escherichia coli RNase P, M1 RNA, and the protein subunit, C5, in particular with
      respect to cleavage-site selection. Recent genetic and biochemical data show that
      the two C residues in the 3'-terminal CCA sequence of a precursor interact with
      the enzyme through Watson-Crick base-pairing. This is suggested to result in
      unfolding of the amino acid acceptor-stem and exposure of the cleavage site.
      Furthermore, other close contact points between M1 RNA and its substrate have
      recently been identified. These data, together with the two existing three
      dimensional structure models of M1 RNA in complex with its substrate, establish a
      platform that will enable us to seek an understanding of the underlying mechanism
      of cleavage by this elusive enzyme.

PMID- 8559061
TI  - Why does Escherichia coli recycle its cell wall peptides?
AB  - This review discusses the phenomenon of recycling of cell wall peptides. It is a
      major, though non-essential, pathway of the cell and is required for induction of
      beta-lactamase. Consequently, the recycling pathway is viewed as a possible
      signalling vehicle, informing the cell of the condition of the murein sacculus,
      an essential structure existing outside the cell itself. As the study of this
      phenomenon is in its infancy, several speculations are offered for a possible
      regulatory function.

PMID- 8559062
TI  - Maturation pathway of nisin and other lantibiotics: post-translationally modified
      antimicrobial peptides exported by gram-positive bacteria.
AB  - Lantibiotics form a family of highly modified peptides which are secreted by
      several Gram-positive bacteria. They exhibit antimicrobial activity, mainly
      against other Gram-positive bacteria, by forming pores in the cellular membrane.
      These antimicrobial peptides are ribosomally synthesized and contain leader
      peptides which do not show the characteristics of signal sequences. Several amino
      acid residues of the precursor lantibiotic are enzymatically modified, whereafter
      secretion and processing of the leader peptide takes place, yielding the active
      antimicrobial substance. For several lantibiotics the gene clusters encoding
      biosynthetic enzymes, translocator proteins, self-protection proteins, processing
      enzymes and regulatory proteins have been identified. This MicroReview describes
      the current knowledge about the biosynthetic, immunity and regulatory processes
      leading to lantibiotic production. Most of the attention is focused on the
      lantibiotic nisin, which is produced by the food-grade bacterium Lactococcus
      lactis and is widely used as a preservative in the food industry.

PMID- 8559063
TI  - An intron-containing meiosis-induced recombination gene, rec15, of
      Schizosaccharomyces pombe.
AB  - Mutations in the rec15 gene of Schizosaccharomyces pombe reduce meiotic
      recombinant frequencies, in the three intervals tested, as much as 1000-fold but
      have no detectable mitotic phenotype. The rec15 gene was mapped to within 1 cM of
      mat1. The gene was cloned by genetic complementation and its nucleotide sequence
      determined. Deletion analysis and gene replacement confirmed that the clones
      contained the rec15 gene on DNA fragments as short as 1.3 kb. The nucleotide
      sequence of the 1.3 kb fragment predicted that rec15 had a 49 bp intron
      separating two exons encoding a 180-amino-acid polypeptide product. This
      predicted intron was confirmed by reverse transcriptase-polymerase chain reaction
      (RT-PCR) analysis. During thermally induced meiosis in a pat1-114 (Ts) mutant,
      the rec15 transcripts were induced to maximal levels at 2-3h but were present at
      much lower levels before and after this time. The transient induction of the
      transcripts and the phenotype of a rec15 null (deletion) mutation suggest that
      the rec15 gene product is required during the early stages of meiosis for meiotic
      recombination.

PMID- 8559064
TI  - The extreme C-terminus is required for secretion of both the native
      polygalacturonase (PehA) and PehA-Bla hybrid proteins in Erwinia carotovora
      subsp. carotovora.
AB  - A set of gene fusions was constructed between the pehA gene encoding the secreted
      endopolygalacturonase (PehA) and the bla gene coding for a normally periplasmic
      beta-lactamase (Bla). The resulting hybrid proteins were specifically and
      actively routed out of the cells via the Out-terminal branch of the general
      secretory pathway (GSP) in Erwinia carotovora subsp. carotovora (Ecc), provided
      that no more than the last two amino acids (aa) of the PehA domain were excluded
      from the fusion. However, both PehA-Bla hybrid proteins and PehA variants lacking
      at least four aa from the C-terminus of the PehA accumulated in the periplasm.
      Also, overexpression of the gene fusions prevented extracellular targeting of the
      hybrid proteins. Site-directed mutagenesis of the codons -4 and -3 (encoding Asn
      373 and Val-374, respectively) from the end of the pehA gene and analysis of the
      protein products suggested that the Val-374 was important both for the structure
      and secretion of PehA, while the Asn-373 proved to be insignificant. We conclude
      that: (i) the GSP of Ecc is capable of secreting heterologous proteins; (ii) as
      the PehA protein can accommodate C-terminal extensions, secretion can occur with
      no part of the proposed targeting signal lying within the C-terminal extremity of
      a secreted molecule; and (iii) residues within the C-terminus of PehA play a role
      in secretion, possibly through stabilization of a structure needed for proper
      exposition of the proposed targeting motif.

PMID- 8559065
TI  - MxiG, a membrane protein required for secretion of Shigella spp. Ipa invasins:
      involvement in entry into epithelial cells and in intercellular dissemination.
AB  - Entry of Shigella flexneri into epithelial cells involves secretory proteins, the
      Ipa proteins, and their dedicated secretion apparatus, the Mxi-Spa translocon,
      which is encoded by the mxi and spa operons. We have characterized the mxiG gene
      that is located at the proximal part of the mxi operon. Inactivation of mxiG
      abolished lpa secretion, which indicates that MxiG is an essential component of
      the Mxi-Spa translocon. Immunoblotting analysis of membrane fractions suggests
      that the 42 kDa MxiG protein is associated with both the inner and outer
      membranes. Taking advantage of the complementation of the mxiG mutant by a
      plasmid carrying a wild-type copy of mxiG (which restored Ipa secretion, entry
      into HeLa cells, and cell-to-cell spread) we mutagenized the mxiG gene carried by
      the complementing plasmid to replace the RGD motif of MxiG by RAD. This mutation
      (mxiG*), which had no effect on the stability of the protein, did not affect Ipa
      secretion in vitro or entry into HeLa cells, but impaired intercellular
      dissemination. Therefore, MxiG and possibly proteins secreted by the Mxi-Spa
      translocation are involved not only in entry but also in spread of Shigella
      between epithelial cells.

PMID- 8559066
TI  - Analysis of an Escherichia coli mutant TyrR protein with impaired capacity for
      tyrosine-mediated repression, but still able to activate at sigma 70 promoters.
AB  - In Escherichia coli, TyrR represses and activates transcription of operons
      required for tyrosine, phenylalanine and tryptophan biosynthesis and uptake. The
      TyrR central domain is homologous with NtrC and some other bacterial regulatory
      proteins, although TyrR regulates sigma 70, not sigma 54, promoters. We isolated
      a central domain TyrR mutant (TyrR E274Q) by substitution of a normally conserved
      amino acid. The mutant was unable to bring about tyrosine-mediated repression of
      aroF, aroL, tyrB, and tyrP and had diminished capability for tyrosine- and
      phenylalanine-mediated repression of aroP. In contrast, it was able to effect
      wild-type levels of phenylalanine-mediated repression of aroG, tryptophan
      mediated repression of aroP and transcriptional activation of mtr and tyrP. The
      binding of purified TyrR E274Q to ATP (a requirement for tyrosine binding) and to
      the strong TyrR box of tyrP operator DNA were normal, but tyrosine binding and
      tyrosine-dependent hexamerization were significantly impaired. These properties
      are consistent with the proposal that self association is essential for tyrosine
      mediated repression by TyrR but not for tyrosine- or phenylalanine-mediated
      activation. E274 of TyrR must participate in either the binding of tyrosine, or
      the coupling of ATP binding with a conformational change that alters the affinity
      of the ATP-dependent aromatic amino acid-binding site.

PMID- 8559067
TI  - Evidence for two aromatic amino acid-binding sites, one ATP-dependent and the
      other ATP-independent, in the Escherichia coli regulatory protein TyrR.
AB  - In Escherichia coli, genetic regulation of aromatic amino acid biosynthesis and
      uptake is effected by the protein TyrR, which acts via ligand-mediated repression
      and activation. Characterization of the interactions of tyrosine, phenylalanine
      and tryptophan with TyrR revealed the presence of two separate aromatic amino
      acid-binding sites, one ATP-dependent, the other ATP-independent. Binding to the
      ATP-dependent site induces the self-association of TyrR. Using sedimentation
      equilibrium analyses, dissociation constants for this site in the dimeric and
      hexameric forms of TyrR were determined to be 330 microM and 24 microM,
      respectively, for tyrosine, and 55 mM and 3.7 mM, respectively, for
      phenylalanine. Tryptophan bound with a strength similar to that of phenylalanine,
      and both phenylalanine and tryptophan competed with the binding of tyrosine. The
      ATP-independent site, which has not been observed previously, was characterized
      by ultraviolet (u.v.) difference spectroscopy and a sedimentation-velocity
      meniscus-depletion method. Phenylalanine bound co-operatively to this site,
      exhibiting half-saturation at 260 microM. Tryptophan competed weakly with
      phenylalanine, half-saturation occurring at 1.2 mM. No binding of tyrosine to
      this site could be detected. We propose that the binding of phenylalanine or
      tryptophan to this ATP-independent site is responsible for phenylalanine- and
      tryptophan-mediated regulation by TyrR.

PMID- 8559068
TI  - Transcription-induced deletions in Escherichia coli plasmids.
AB  - Characterization of functions that render DNA susceptible to rearrangement is
      important for a better understanding of genome instability. In a previous work,
      we showed that sequences located downstream of a strong promoter are particularly
      prone to deletion. In this paper, the parameters that influence transcription
      induced deletions were studied. pBR322 derivatives carrying the M13 (+)
      replication origin and a PTac-dependent transcription region were used. Deletion
      formation was analysed in the presence of the replication protein of M13, which
      introduces a nick at the phage replication origin, and in a rep- strain to avoid
      M13-driven replication. Our study showed that: (i) 4 h after induction of
      transcription, a few per cent of the plasmids have experienced a deletion; (ii)
      these deletions result in joining of the M13 replication origin to a nucleotide
      located in or downstream of the transcribed region; (iii) deletion formation
      strongly depends on the orientation of transcription, on promoter strength and
      transcript length, but is independent of translation; (iv) formation of
      transcription-induced supercoiling domains does not induce deletion formation. We
      propose that deletions in the transcribed region result from collisions between
      converging replication and transcription machineries.

PMID- 8559069
TI  - Direct regulation of the ATPase activity of the transcriptional activator DmpR by
      aromatic compounds.
AB  - The NtrC-like regulator DmpR controls transcription from the dmp operon that
      encodes the enzymes for catabolism of phenol and some related aromatic compounds.
      DmpR activates transcription from the sigma 54-dependent dmp-operon promoter in
      the presence of pathway substrates or structural analogues in the growth medium.
      Using affinity-purified DmpR and a truncated derivative, we show here that
      aromatic compounds directly activate the ATPase activity of this protein in
      vitro, and that the amino-terminal domain represses this activity in the absence
      of an aromatic ligand. In order to dissect the activation process, derivatives of
      DmpR exhibiting single amino acid changes were isolated and their effector
      dependence and specificity profiles were analysed in vivo. The mechanistic
      implications of the phenotypes of these mutants are discussed.

PMID- 8559070
TI  - Functional analysis of the pediocin operon of Pediococcus acidilactici PAC1.0:
      PedB is the immunity protein and PedD is the precursor processing enzyme.
AB  - The bacteriocin pediocin PA-1 operon of Pediococcus acidilactici PAC1.0
      encompasses four genes: pedA, pedB, pedC and pedD. Transcription of the operon
      results in the formation of two overlapping transcripts, probably originating
      from a single promoter upstream of pedA. The major transcript comprises pedA,
      pedB, and pedC, while a minor transcript encompasses all of these genes and pedD.
      By deletion analysis and overexpression of pedB in Pediococcus pentosaceus we
      demonstrate that this gene encodes the pediocin PA-1 immunity protein.
      Prepediocin is active in Escherichia coli and when pedA was expressed
      concomitantly with pedD both the precursor and the mature form of pediocin were
      observed intracellularly. Extracellular pediocin was only detected if both pedC
      and pedD were present. The N-terminal domains of PedD and a subgroup of
      bacteriocin ABC-transporters are conserved. Expression of only this domain of
      PedD in cells producing prepediocin was sufficient for prepediocin processing.
      From these results we conclude that both PedC and PedD are essential for pediocin
      transport, and that PedD is capable of processing prepediocin.

PMID- 8559071
TI  - Salmonella typhimurium responses to a bactericidal protein from human
      neutrophils.
AB  - Bactericidal/permeability-increasing protein [BPI] is a cationic antimicrobial
      protein from neutrophils that specifically binds to the surfaces of Gram-negative
      bacteria via the lipid A component of lipopolysaccharide. To obtain information
      about the responses of Salmonella typhimurium to cell-surface damage by BPI, two
      dimensional gel electrophoresis and N-terminal microsequencing were used to
      identify proteins that were induced or repressed following BPI treatment. The
      majority of the affected proteins are involved in central metabolic processes.
      Upon addition of BPI, the beta-subunit of the F1 portion of Escherichia coli ATP
      synthase was repressed threefold whereas six proteins were induced up to 11-fold.
      Three of the latter were identified as lipoamide dehydrogenase, enoyl-acyl
      carrier protein reductase, and the heat-shock protein HtpG. Additionally, a novel
      protein, BipA, was identified that is induced over sevenfold by BPI; sequence
      analysis suggests that it belongs to the GTPase superfamily and interacts with
      ribosomes. A conserved direct-repeat motif is present in the regulatory regions
      of several BPI-inducible genes, including the bipA gene. Only one of the BPI
      responsive proteins was induced when cells were treated with polymyxin B, which
      also binds to lipid A. We therefore conclude that BPI and polymyxin B affect
      different global regulatory networks in S. typhimurium even though they bind with
      high affinity to the same cell-surface component.

PMID- 8559072
TI  - Characterization of pra, a gene for replication control in pSAM2, the integrating
      element of Streptomyces ambofaciens.
AB  - pSAM2 is a genetic element found integrated in Streptomyces ambofaciens (B2) and
      additionally in a replicating form in two mutants B3 and B4. The presence of the
      pSAM2 replicating form in these mutants was the result of mutations located on
      pSAM2 in the pra locus, named pra3 and pra4, respectively. The pra gene is not
      directly involved in replication, but its inactivation led to the disappearance
      of the pSAM2 free form; therefore, it was considered as a replication regulator.
      The pra3 and pra4 mutations were located in the pra promoter and were shown to be
      point substitutions that increase the promoter strength. The replication
      regulator role of pra was demonstrated by the fact that its constitutive
      expression in cells harbouring pSAM2B2, which is normally only integrated, led to
      the appearance of the pSAM2 replicating form. Northern analysis showed that the
      pra gene transcript can be detected only for the replicating mutants B3 and B4
      and that the three adjacent genes korSA, pra and traSA were transcribed
      separately. As replication of pSAM2 is not needed for its maintenance but is an
      indispensable stage of its transfer, the pra gene, described formally as an
      activator of pSAM2 replication, is patently involved in pSAM2 transfer.

PMID- 8559073
TI  - Detection of induced beta-galactosidase activity in individual non-culturable
      cells of pathogenic bacteria by quantitative cytological assay.
AB  - One Escherichia coli and two F' lac+ Salmonella strains were carbon and nitrogen
      stressed at 37 degrees C over 35 days in the presence or absence of
      chloramphenicol; the number, activity and culturability of cells in the resultant
      populations were studied. Active cells were enumerated by fluorescence microscopy
      after treatment with the lac inducer IPTG and cytological assay for beta
      galactosidase. In all experiments, active and total cell counts remained within a
      three-fold range of each other and their initial values, while culturability fell
      by > 10(8)-fold and 10(3)-fold in chloramphenicol-treated and untreated
      preparations, respectively. Quantitative image analysis revealed different
      distributions of cell-specific fluorescence and indicated a progressive decline
      in the levels of induced enzyme activity in both E. coli and Salmonella
      enteritidis. It was concluded that the non-culturable cells studied retained
      inducible enzyme activity and that this activity did not result from a starvation
      induced programme of gene expression. Whether or not such active but non
      culturable cells are viable, they are clearly responsive and have the potential
      to influence their environment. The assay described can be applied to
      heterogeneous populations and environments and shows considerable potential for
      the study of gene expression at the single cell level.

PMID- 8559074
TI  - Identification and characterization of a cell envelope protein of Haemophilus
      influenzae contributing to phase variation in colony opacity and nasopharyngeal
      colonization.
AB  - Haemophilus influenzae undergoes spontaneous phase variation in colony
      morphology. Organisms from transparent colonies efficiently colonize the
      nasopharynx in an infant rat model of H. influenzae carriage, whereas organisms
      from more opaque colonies are deficient at colonization. A genetic approach
      relying on the transformability of H. influenzae was used to identify a locus
      contributing to opacity variation. By screening a library of chomosomal DNA from
      an opaque variant of strain Rd, it was possible to isolate a single clone capable
      of transforming a transparent Rd host to a more opaque phenotype. A region
      containing two genes, designated oapA and oapB, was identified. The deduced amino
      acid sequence of oapB has similarity to a consensus sequence for bacterial
      lipoproteins. Genetically defined mutations in oapA were transformed into the
      transparent Rd to confirm that this gene is required for expression of the
      transparent colony phenotype. Although oapA lacks a signal sequence, gene fusions
      to phoA show that OapA is secreted in H. influenzae and undergoes phase variation
      in expression. Mutagenesis of oapA in strain Rd, and type b strain Eagan,
      resulted in loss of the ability to colonize the nasopharynx of infant rats. The
      type b mutant, however, was as virulent as its parent strain when inoculated
      intraperitoneally. This suggests that the contribution of OapA to pathogenesis is
      limited to events associated with colonization of the mucosal surface.

PMID- 8559075
TI  - Identification of base pairs important for OmpR-DNA interaction.
AB  - OmpR, the transcriptional regulator of the ompF and ompC porin genes, is a member
      of a novel class of DNA-binding proteins. The mechanism(s) by which this class of
      proteins interacts with target DNA sites is not understood. To address this
      issue, we investigated the nature of the DNA sequences recognized by OmpR. A 36
      bp DNA fragment was identified that is capable of supporting OmpR-DNA interaction
      in vivo. The base pairs within this region of DNA that are critical to this
      interaction were identified by isolating mutations within the fragment that
      hinder normal OmpR-DNA binding. The results obtained provide insights concerning
      the nature of the sequences recognized by OmpR and also support a model in which
      co-operative binding is involved in OmpR-DNA interaction.

PMID- 8559076
TI  - A novel locus of Yersinia enterocolitica serotype O:3 involved in
      lipopolysaccharide outer core biosynthesis.
AB  - Yersinia enterocolitica serotype O:3 strain 6471/76-c (YeO3-c) was sensitive to
      bacteriophage phi R1-37 when grown at 37 degrees C but not when grown at 22
      degrees C because of steric hindrance by abundant lipopolysaccharide (LPS) O-side
      chain (O-antigen) expressed at 22 degrees C. The transposon library of YeO3-c was
      grown at 37 degrees C and screened for phage phi R1-37-resistant transposon
      insertion mutants. Three types of mutant were isolated: (i) phage receptor
      mutants expressing O-antigen (LPS-smooth), (ii) phage receptor mutants not
      expressing O-antigen (LPS-rough), and (iii) LPS-smooth mutants with the phage
      receptor constitutively sterically blocked. Mutant type (i) was characterized in
      detail; the transposon insertion inactivates an operon, named the trs operon. The
      main findings based on this mutant are: (i) the frs operon is involved in the
      biosynthesis of the LPS outer core in YeO3-c; the nucleotide sequence of the trs
      operon revealed eight novel genes showing similarly to known polysaccharide
      biosynthetic genes of various Gram-negative bacteria as well as to capsule
      biosynthesis genes of Staphylococcus aureus; (ii) the biosynthesis of the core of
      YeO3-c involves at least two genetic loci; (iii) the trs operon is required for
      the biosynthesis of the bacteriophage phi R1-37 receptor structures; (iv) the
      homopolymeric O-antigen of YeO3-c is ligated to the inner core in Y.
      enterocolitica O:3; (v) the trs operon is located between the adk-hemH and galE
      gsk gene pairs in the Y. enterocolitica chromosome; and (vi) the phage phi R1-37
      receptor is present in many but not in all Y. enterocolitica serotypes. The
      results also allow us to speculate that the trs operon is a relic of the
      ancestral rfb region of Y. enterocolitica O:3 carrying genes indispensable for
      the completion of the core polysaccharide biosynthesis.

PMID- 8559077
TI  - RNase K: one less letter in the alphabet soup.

PMID- 8559078
TI  - Comment on the Microreview by Conrad Woldringh (Significance of plasmolysis
      spaces as markers for periseptal annuli and adhesion sites. Mol Microbiol, 1994,
      14: 597-607)

PMID- 8559079
TI  - Fur regulation in Yersinia species.

PMID- 8559080
TI  - Detection and partial characterization of Pasteurella multocida found in feline
      skin lesions.
AB  - Pasteurella multocida was isolated from 21 of 105 purulent skin lesions in
      household cats. The bacterium was in pure culture in nine specimens and
      predominant in six specimens. Its viable counts were 10(2) to 10(7) colony
      forming units/ml. Of 21 isolates of P. multocida, seventeen were considered to be
      capsular type A. The predominant capsular and somatic type was the serotype
      A:3,4. Inoculation of the filter-sterilized supernatants of the isolates induced
      an erythematous response in guinea pig skins. These findings suggest that P.
      multocida is a candidate as a pathogen of feline skin lesions and the erythema
      inducing activity of the bacterium may participate in the formation of skin
      lesions in household cats.

PMID- 8559081
TI  - The pattern of respiratory burst of leucocytes in patients with Echinococcus
      granulosus.
AB  - The function of polymorphonuclear leucocytes (PMN) of patients with hydatidosis
      was investigated. The patients were divided into three categories according to
      the characteristics of the cyst (calcified, alive and dead cyst). Healthy blood
      donors were used as a control group. The oxidative activity of PMN was determined
      by chemiluminescence (CL) assay. Reduction of ferricytochrome C was used to
      measure the superoxide (O2-) production. Phagocytosis was monitored by opsonized
      yeast uptake. The results showed that the CL response, O2- production and
      phagocytic index of PMN, significantly increased in patients with dead cysts
      compared with healthy subjects while in patients with live cysts there was a
      marked reduction. No significant changes were noticed in patients with calcified
      cysts. These data indicate that the PMN of infected patients were in an activated
      state both functionally and metabolically.

PMID- 8559082
TI  - Utilization of water hyacinth cellulose for production of cellobiase-rich
      preparation by Aspergillus niger 1.
AB  - Production of a cellobiase-rich preparation by Aspergillus niger 1 was achieved
      using water hyacinth cellulose as the sole carbon source in the culture medium.
      Production of cellobiase, carboxymethylcellulase (CMC-ase) and filter paper (FP)
      cellulase was favoured by controlling the pH of the culture medium during
      fermentation at 5.0. Sodium citrate (0.5%), sodium phytate (0.1%), Tween-80
      (0.2%, v/v) and asparagine (0.07%) had stimulating effects on the productivity of
      cellobiase, CMC-ase and FP-cellulase. Potassium dihydrogen phosphate doubled the
      yield of CMC-ase but had a slight effect on FP-cellulase and cellobiase. Wheat
      bran had a pronounced stimulating effect on the production of cellobiase and CMC
      ase. The combined effects of these stimulators resulted in an enzyme preparation
      rich in cellobiase and contained 18.5, 0.29 and 2.21 U/ml of cellobiase, FP
      cellulase and CMC-ase, respectively. A high cellobiase/FP-cellulase ratio of
      63.8:1 was thus obtained with the fungal enzyme preparation. The cellobiase
      activity was maximal at pH 5.0 and showed good thermostability.

PMID- 8559083
TI  - AH17, a new non-polyenic antifungal antibiotic produced by a strain of
      Spirillospora.
AB  - An antibiotic (AH17) was produced by Spirillospora strain 719. This substance was
      obtained only from the broth filtrate after precipitation with acetic acid
      followed by extraction with n-butanol. Its purification was carried out by thin
      layer chromatography on silica gel followed by HPLC procedures. It showed
      activity against Gram-positive and Gram-negative bacteria and fungi. The
      spectroscopic and chemical properties were examined and indicated that AH17 was a
      quinone. It seems that this is a new antibiotic from Spirillospora.

PMID- 8559084
TI  - The advent of mergers. A new type of group practice is taking shape in Michigan.

PMID- 8559085
TI  - Last in series of PO site visits offers valuable insights into PO success.

PMID- 8559086
TI  - Withdrawal of life support.

PMID- 8559087
TI  - Extended hospital stays with increasing age: the impact of an acute geriatric
      unit.
AB  - OBJECTIVES: To examine the association between increasing age and extended length
      of hospitalisation, and the impact of an acute geriatric unit on this
      association. DESIGN: Retrospective analysis of concurrently collected data of
      patients admitted to three general medical units, one of which was an acute
      geriatric unit. SETTING: Alfred Hospital, Melbourne (a tertiary referral teaching
      hospital), between 1 July 1993 to 30 June 1994. PATIENTS: Those classified into
      the same diagnosis-related groups (DRGs) as the 15 most common DRGs of the acute
      geriatric unit. OUTCOME MEASURE: Incidence of patients with extended lengths of
      stay ("high outliers"), analysed by age, medical unit and DRG. RESULTS: Of 3499
      patients discharged from the hospital with the 15 study DRGs, 303 patients (8.6%)
      were from the acute geriatric unit, and 274 and 300 patients (7.8% and 8.5%) were
      from the two other general medical units, respectively. Patients in the acute
      geriatric unit were significantly older (median age group, 75-79; age range, 18
      98) than patients in all other hospital units (median age group, 60-64; age
      range, 18-97) (P < 0.0001). Analysis of patients with respiratory and
      cardiovascular DRGs admitted to all general medical units compared with specialty
      units showed this age discrepancy was even more marked for patients aged over 85.
      There was an increased likelihood (P < 0.001) of an extended length of stay for
      patients aged over 55. The incidence of high outliers for comparable DRGs was
      lower for patients cared for by the acute geriatric unit, compared with general
      medical units. In the acute geriatric unit, unlike the overall trend, the
      proportion of high outliers did not increase with age. CONCLUSIONS: The
      specialised management of acute geriatric medical units can counteract the trend
      towards increased incidence of high outliers with increasing age, despite
      significantly older patients.

PMID- 8559088
TI  - Physical, sexual and emotional violence against women: a general practice-based
      prevalence study.
AB  - OBJECTIVE: To determine the prevalence of domestic violence, childhood abuse and
      sexual assault experienced by women attending general practitioners. DESIGN: A
      cross-sectional, questionnaire-based prevalence survey. SETTING: 15 general
      practices in metropolitan Melbourne between November 1993 and February 1994.
      SUBJECTS: 3026 women over the age of 18 attending for a consultation. RESULTS:
      The response rate was 72%. Over a quarter of women in relationships had been
      victims of physical or emotional partner abuse in the previous year, one in 10
      having experienced severe physical violence. Thirteen percent of women had
      experienced rape or attempted rape, 10% had been severely beaten during childhood
      and 28% had experienced childhood sexual abuse involving physical contact. The
      abuse had been disclosed to the woman's doctor by only 27% of those who had
      experienced partner or childhood physical abuse (mostly because the doctor had
      never asked) and 9% of those who had experienced sexual abuse (mostly because the
      woman did not see it as relevant to the consultation). CONCLUSION: There is a
      high prevalence of physical, sexual and emotional violence against women as well
      as poor communication about this violence to their general practitioners.
      RECOMMENDATION: Medical practitioners should be more proactive in questioning
      women about violence.

PMID- 8559089
TI  - Human hydatidosis in New South Wales and the Australian Capital Territory, 1987
      1992.
AB  - OBJECTIVE: To determine the prevalence of human hydatidosis in New South Wales
      and the Australian Capital Territory. METHODS: Data on human hydatid infection
      occurring between 1987 and 1992 were collected retrospectively from 25 hospitals
      and 13 health services in New South Wales and four hospitals in the Australian
      Capital Territory. Mean annual prevalences of human hydatidosis were determined
      for shires in eastern New South Wales and data on infection in immigrants and
      Australian-born patients were compared. RESULTS: 321 patients were diagnosed with
      hydatid disease, 1987-1992; 195 were new cases and 117 readmissions (nine cases
      were not identified as new or recurrent). Most patients lived in the eastern half
      of New South Wales (which includes the Australian Capital Territory), half in
      rural areas and half in the major coastal cities. Most Australian-born rural
      patients lived in 39 shires in the north-eastern and south-eastern Tablelands.
      Sixty per cent of the patients in major cities were born overseas. CONCLUSIONS:
      Hydatid infection occurs more commonly in south-eastern Australia than the
      official figures suggest. In rural areas of the north-eastern and south-eastern
      Tablelands hydatid infection is of public health importance. The national
      notification system must be improved and control campaigns alerting the public to
      the dangers of hydatid infection promoted.

PMID- 8559090
TI  - Relevance of body weight to apolipoprotein levels in Australian children.
AB  - OBJECTIVES: To assess weight and apolipoprotein profiles in a representative
      sample of primary school children. PARTICIPANTS AND SETTING: 1543 children (936
      girls and 607 boys) aged 6-11 years from schools in the Eastern Sydney Area
      Health Service region in 1994. METHODS: We measured body mass index (BMI) and
      capillary blood apolipoprotein (apo) B and A-I levels (the carrier proteins for
      low and high density lipoprotein cholesterol, respectively) as well as
      lipoprotein (Lp) (a). We related BMI levels to those documented in the 1985
      Australian Council on Health, Physical Education and Recreation (ACHPER) survey
      of school children. RESULTS: Compared with the ACHPER distribution, BMI was
      increased in the boys but not in the girls; 16.8% of boys were above the 90th
      percentile of the ACHPER distribution (P = 0.003) and only 6.5% were below the
      10th percentile (P = 0.046). There were 45 boys (7.4%) and 53 girls (5.7%) with
      BMIs above the 95th percentile who were, by definition, obese. They had highly
      significant increases in apo B (P = 0.003) and apo B: apo A-I ratio (P = 0.0001)
      compared with children in the normal BMI range (10th-90th percentiles); and 20%
      of the population, including the obese group, also had Lp(a) levels greater than
      300 mg/L. The results in children aged 10 and 11 years were not different from
      those of the whole group, consistent with an absence of possible confounding
      effects due to early puberty or smoking. CONCLUSIONS: There was an increase in
      weight relative to height in boys aged 6-11 years in eastern Sydney, compared
      with the 1985 ACHPER survey. In both boys and girls with the highest BMI
      category, levels of apo B and the apo B: apo A-I ratio were significantly
      increased. As these apolipoprotein changes are correlated closely with early
      onset atherogenesis and are correctable, their identification offers prospects
      for prevention.

PMID- 8559091
TI  - Workers' compensation--what role the doctor?

PMID- 8559092
TI  - Donation of heart valve tissue: seeking consent and meeting the needs of donor
      families.
AB  - OBJECTIVE: To report on the experiences of senior social workers in seeking
      consent for donation of heart valve tissue at coronial autopsies. METHODS:
      Retrospective review of the records of an allograft heart valve program at a
      tertiary referral hospital in Brisbane between 11 October 1990 and 11 October
      1995. RESULTS: Of the 305 families who could be contacted after the sudden death
      of a family member, 247 consented to donation (81%) and 58 did not (19%). In the
      context of coronial enquiries, a sensitive assessment of the counselling needs of
      potential donor families is necessary. Difficulties in seeking consent include:
      the sudden nature of the death and lack of information about the prospective
      donor and his/her family; and the limited time available for tissue retrieval as
      well as the necessity, in most cases, to obtain consent for donation by
      telephone. The needs of these families included information on autopsy,
      transplantation and recipient outcome; grief counselling; emotional and practical
      support; and recognition of their contribution. CONCLUSION: In this successful
      tissue donation program, senior social workers have maximised the availability of
      heart valve tissue for donation, while respecting the needs and wishes of
      potential donor families and helping them with their loss through counselling and
      assistance. The program has been extended to the retrieval of eye and bone tissue
      at coronial autopsies in Queensland.

PMID- 8559093
TI  - Techniques to reduce the discomfort of paediatric laceration repair.
AB  - The wide variety of techniques now available to provide analgesia and sedation in
      children undergoing laceration repair include needle-free techniques of wound
      repair, alternative methods of local anaesthetic infiltration, and non
      pharmacological interventions. Knowledge and use of these options will help the
      practitioner limit a child's distress.

PMID- 8559094
TI  - Panic in the potting shed. The association between Legionella longbeachae
      serogroup 1 and potting soils in Australia.
AB  - Is gardening a health hazard? Legionella longbeachae, a potential cause of
      pneumonia, has been found in Australian potting media. However, further research
      is needed to determine its clinical relevance in this situation. This did not
      stop the popular media linking two deaths from Legionella infection in Queensland
      to potting mix exposure.

PMID- 8559095
TI  - Aminoglycoside dosing: one, two or three times a day?
AB  - The safety and efficacy of conventional aminoglycoside dosing regimens have been
      proven in clinical trials. Higher doses at longer intervals may be more effective
      if they result in higher peak serum levels of the drug, but few trials of "once-a
      day" dosing have shown improved clinical outcome. The clinical safety of allowing
      trough serum levels to fall below the minimum inhibitory concentration is not
      established. Literal "once-a-day" dosing will result in drug accumulation and
      toxicity in patients with reduced renal clearance, and in potential lack of
      efficacy and the emergence of antibiotic-resistant organisms in those with
      increased renal clearance. However, modified "once-a-day" dosing, with the
      interval determined by the individual's renal clearance rate (hence avoiding
      subtherapeutic trough levels), will avoid these problems.

PMID- 8559096
TI  - Syndrome X (insulin resistance metabolic syndrome): a deadly quartet or an
      awesome foursome?

PMID- 8559097
TI  - Psychosocial support, treatment of metastatic disease and palliative care.
AB  - This article deals with four linked but distinct aspects of care for women with
      breast cancer, with an emphasis on the pivotal role of the general practitioner:
      1. Modern medicine is fast recognising the need for psychosocial support of
      patients; in fact, for an integrated approach to caring for the whole person at
      all stages of illness. 2. Oncological treatment of metastatic disease needs to be
      individualised and based on realistic expectations of outcome balanced against
      side effects. 3. An open dialogue about the role and appropriateness of so-called
      "alternative" or "complementary" therapies is needed. 4. Despite significant
      improvements in palliative care quality and access in Australia in the last
      decade, many practitioners still require support and advice in this demanding
      area of care (particularly about difficult symptom control).

PMID- 8559098
TI  - Optimum care of the elderly in an acute general hospital.

PMID- 8559099
TI  - The diabetes epidemic in Australia: could undiagnosed diabetes in pregnancy be
      part of the cause?

PMID- 8559100
TI  - The diabetes epidemic in Australia: prevalence, patterns and the public health.

PMID- 8559101
TI  - Pharmaceutical Benefits Advisory Committee: some questions answered.

PMID- 8559102
TI  - Pharmaceutical Benefits Advisory Committee: some questions answered.

PMID- 8559103
TI  - Asymptomatic carotid stenosis: how should it be managed.

PMID- 8559104
TI  - Differences in work activities between private and community health centre GPs.

PMID- 8559105
TI  - Clinical practice guidelines.

PMID- 8559106
TI  - Marfan syndrome in aboriginals.

PMID- 8559107
TI  - General practitioner attitudes to recall systems for cervical screening.

PMID- 8559108
TI  - Snakes and ladders: getting patients into metropolitan public hospitals.

PMID- 8559109
TI  - Deaths attributed to an "ecstasy" overdose.

PMID- 8559110
TI  - Septic arthritis secondary to toothpick penetration.

PMID- 8559112
TI  - Enter the Web: an experiment in electronic research peer review.

PMID- 8559111
TI  - Hydatid disease: medical problems, veterinary solutions, political obstacles.

PMID- 8559113
TI  - Systemic antifungal drugs.

PMID- 8559114
TI  - Acarbose for diabetes mellitus.

PMID- 8559115
TI  - The potential health impacts of climate change: an overview.
AB  - Climate change would have a range of impacts on human health. Health impacts
      would be caused by the direct effect of climatic factors on human health, such as
      heat stress, and possible changes in the frequency and intensity of extreme
      weather events such as storms, floods and droughts. Impacts on health would also
      be mediated by the indirect effects of climate change, such as changes in
      availability of food and water and the distribution of vector-borne diseases. The
      majority of health impacts would be adverse and would depend greatly on the
      vulnerability of populations.

PMID- 8559116
TI  - Climate change and human health: possible communicable disease consequences in
      the United Kingdom.
AB  - In May 1990 a 'Think Tank' was constituted in order to advise the Director of the
      Public Health Laboratory Service (PHLS) on the potential effects of global
      climatic change, and of world population increase and movements, on the
      epidemiology of infectious diseases internationally and in the United Kingdom,
      and to consider the implications for the PHLS. This article draws on the Think
      Tank deliberations and describes the scenario considered, and some of the major
      issues identified, with particular reference to the UK.

PMID- 8559117
TI  - Conceptual and methodological challenges in predicting the health impacts of
      climate change.
AB  - Describing (not to mention quantifying) the anticipated adverse health impacts of
      global climate change poses basic challenges to biomedical science. First and
      foremost, it is beset with uncertainties and complexities; it is necessarily an
      'If-Then' exercise, that takes as given climatologists' estimates of the
      plausible range of greenhouse-induced climate change over the coming century. The
      health impacts of climate change would generally not occur via the familiar
      direct-acting mechanisms that characterise local environmentally-induced
      toxicology or pathophysiology; therefore they would lack the mechanistic
      directness-of-effect that epidemiological research methods are best equipped to
      study. Rather, the health impacts would occur on a larger scale, and would result
      predominantly from perturbations of natural biogeochemical systems that reduce
      Earth's capacity for life support. Therefore, scientists will need to address the
      assessment of impacts within an ecological framework, and with an unusually long
      time horizon. This assessment requires a new capacity for systems-based thinking,
      predictive modelling, and dealing with uncertainty. Scientists, policy-makers and
      general public will have to adjust to unfamiliar styles of 'anticipatory'
      science, with an unusual overlay of uncertainty and provisionality.

PMID- 8559118
TI  - Climate change and malaria: exploring the risks.
AB  - That the enhanced greenhouse effect may prove to influence human health will come
      as no surprise. One of the potential health consequences is a change in
      distribution patterns of vector-borne diseases. In tropical countries, such
      diseases are a major cause of illness and death. One of the most important vector
      borne diseases in the world is malaria, which is associated with one of four
      species of parasite and transmitted by a mosquito vector. Climatic conditions,
      and temperature in particular, directly influence mosquito development, feeding
      frequency and longevity of the mosquito, as well as the time in which the
      parasite develops inside the mosquito. Other environmental factors such as
      vegetation and breeding sites are indirectly influenced by climate conditions. In
      order to assess the impact of an anthropogenic climate change on the transmission
      of malaria, an integrated assessment model has been developed. In this integrated
      model, the direct effects of a change in temperature and precipitation on the
      transmission potential of a mosquito population is assessed by means of the
      vectorial capacity. The effect of a human-induced climate change on human health
      is evaluated by assessing the change in malaria prevalence and disease burden. A
      sustainable development index, which is an aggregate of an environmental pressure
      indicator, a health indicator and a socio-economic development indicator is
      introduced and discussed. Such an index can be used to determine whether future
      projections are sustainable.

PMID- 8559119
TI  - The climate change convention and human health.
AB  - The United Nations Framework Convention on Climate Change, signed at Rio in June
      1992, is intended to minimize climate change and its impact. Much of its text is
      ambiguous and it is not specifically directed to health considerations. It is,
      however, recognized that adverse effects of climate change on health are a
      concern of humankind, and health is an integral part of the Convention. The
      Convention includes commitments by the developed countries to reduce emissions of
      greenhouse gases and to increase public awareness of these commitments. The
      significance of the Convention in these respects is discussed critically and
      future developments considered.

PMID- 8559120
TI  - Minding your manners.

PMID- 8559121
TI  - One-on-one cost accounting.

PMID- 8559122
TI  - Otolaryngology quiz #8. Intranasal foreign body.

PMID- 8559123
TI  - Overview of 1995 PIAA Breast Cancer Study.

PMID- 8559124
TI  - The new social engineers of the 90s: Federal Trade Commission (FTC) and the
      Department of Justice anti-trust division (DOJ).

PMID- 8559125
TI  - A new wave of treatments for HIV infection is on the horizon.

PMID- 8559126
TI  - Outcome variations for BPH-TURP patients.

PMID- 8559127
TI  - Barrett's esophagus: a review.
AB  - Complications of Barrett's esophagus include ulceration, stricture, hemorrhage,
      perforation, and the development of malignancy. Barrett's esophagus and
      adenocarcinoma may be diagnosed simultaneously and that gastroesophageal reflux
      symptoms may be absent in many cases. Although endoscopic surveillance is
      justified, no agreement on the frequency can be made. Survival of patients with
      adenocarcinoma in Barrett's esophagus depends on the stage at diagnosis.

PMID- 8559128
TI  - Health status of Asian Pacific Americans in Missouri.
AB  - The dramatic increase in Asian Pacific Americans has created a different set of
      social, economic and health issues for the country as well as for this state.
      Asian Pacific Americans are extremely heterogeneous and bipolar in socioeconomic
      status and health issues. Asian Pacific Islander Americans come from over 43
      countries and speak over 100 languages and dialects. This study reveals that in
      this state, 23% of Asian Pacific American households are linguistically isolated.
      Almost 20% of Asian Pacific American families (married couples with children
      under 5 years old) have an income below the poverty line. The need for severe
      mental health service is four times higher for southeast Asian refugees than the
      overall population. The death rates from communicable disease and suicide are
      lowest for Asian Pacific Americans, and for Asian Pacific Americans, the age
      adjusted death rates are widely different. For example, people with Hawaiian
      background appear to have a high incidence of death from heart disease (363.3 per
      100,000) whereas Chinese experienced a higher incidence of death from cancer
      (70.2 per 100,000). The Asian Pacific Americans have the lowest infant mortality
      rate. This paper suggests that providers, educators and legislators should pay
      more attention to Asian Pacific American communities regarding socioeconomic and
      health care needs to create a healthy and productive community.

PMID- 8559129
TI  - [Malignancy of cancer and its surgical treatment].

PMID- 8559130
TI  - [Surgery in patients with organ dysfunctions].

PMID- 8559131
TI  - [Problems with organ preservation].

PMID- 8559132
TI  - [Advances in heterologous transplantation researches].

PMID- 8559133
TI  - [Recent advances and problems in the diagnosis and therapy of congenital
      deformities].

PMID- 8559134
TI  - [Treatment of progressive rectal cancer].

PMID- 8559135
TI  - [Choice of treatment for hepatocellular carcinoma].

PMID- 8559136
TI  - [Surgical treatment in advance cancer of the mammary gland and endocrine glands].

PMID- 8559137
TI  - [Choices of antineoplastic chemotherapy in cancer surgical patients].

PMID- 8559138
TI  - [Problems in thoracic and abdominal aortic aneurysm surgery].

PMID- 8559139
TI  - [Surgical treatment of the complications of myocardial infarction (heart rupture,
      heart septal perforation)].

PMID- 8559140
TI  - [Diagnosis of non-open injuries].

PMID- 8559141
TI  - [Problems with lung transplantation].

PMID- 8559142
TI  - Two forms of Hox11 a T cell leukemia oncogene, are expressed in fetal spleen but
      not in primary lymphocytes.
AB  - HOX11 is identified from the breakpoint of human T cell acute lymphoblastic
      leukemias with t(10;14). Since overexpression of HOX11 in T cells caused
      leukemias in transgenic mice, the endogenous HOX11 may play a role in
      proliferation and differentiation of T cells. In order to elucidate the role, we
      examined the expression of Hox11 in normal lymphocytes by a reverse transcriptase
      polymerase chain reaction analysis. Two alternatively spliced Hox11 mRNAs were
      expressed in fetal spleens. However, lymphocytes did not express Hox11 mRNA
      during differentiation. Furthermore, it was not induced in primary lymphocytes
      after activation. These results suggest that ectopic expression of HOX11 in T
      cells is responsible for leukemogenesis.

PMID- 8559143
TI  - In vitro and in vivo inhibition of complement activity by a single-chain Fv
      fragment recognizing human C5.
AB  - Complement activation has been implicated in the pathogenesis of several human
      diseases. Recently, a monoclonal antibody, (N19-8) that recognizes the human
      complement protein C5 has been shown to effectively block the cleavage of C5 into
      C5a and C5b, thereby blocking terminal complement activation. In this study, a
      recombinant N19-8 scFv antibody fragment was constructed from the N19-8 variable
      regions, and produced in both mammalian and bacterial cells. The N19-8 scFv bound
      human C5 and was as potent as the N19-8 monoclonal antibody at inhibiting human
      C5b-9-mediated hemolysis of chicken erythrocytes. In contrast, the N19-8 scFv
      only partially retained the ability of the N19-8 monoclonal antibody to inhibit
      C5a generation. To investigate the ability of the N19-8 scFv to inhibit
      complement-mediated tissue damage, complement-dependent myocardial injury was
      induced in isolated mouse hearts by perfusion with Krebs-Henseleit buffer
      containing 6% human plasma. The perfused hearts sustained extensive deposition of
      human C3 and C5b-9, resulting in increased coronary artery perfusion pressure,
      end-diastolic pressure, and a decrease in heart rate until the hearts ceased
      beating approximately 10 min after addition of plasma. Hearts treated with human
      plasma supplemented with either the N19-8 monoclonal antibody or the N19-8 scFv
      did not show any detectable changes in cardiac performance for at least 1 hr
      following the addition of plasma. Hearts treated with human plasma alone showed
      extensive deposition of C3 and C5b-9, while hearts treated with human plasma
      containing N19-8 scFv showed extensive deposition of C3, but no detectable
      deposition of C5b-9. Administration of a 100 mg bolus dose of N19-8 scFv to
      rhesus monkeys inhibited the serum hemolytic activity by at least 50% for up to 2
      hr. Pharmacokinetic analysis of N19-8 scFv serum levels suggested a two
      compartment model with a T1/2 alpha of 27 min. Together, these data suggest the
      recombinant N19-8 scFv is a potent inhibitor of the terminal complement cascade
      and may have potential in vivo applications where short duration inhibition of
      terminal complement activity is desirable.

PMID- 8559144
TI  - Isolation of LERK-5: a ligand of the eph-related receptor tyrosine kinases.
AB  - Hek and elk are members of the eph-related family of receptor tyrosine kinases.
      Recently we isolated four cDNAs encoding membrane-bound ligands to hek and elk
      [Beckman et al. (1994) EMBO J. 13, 3757-3762; Kozlosky et al. (1995) Oncogene 10,
      299-306]. Because of the promiscuous nature of their binding, we have termed
      these proteins ligands of the eph-related kinases or LERKs. A search of GenBank
      revealed an expressed sequence tag (EST) with homology to the LERKs. Using this
      EST as a probe, we have isolated human and murine cDNAs that encode a protein
      which we call LERK-5. The human and murine cDNAs encode proteins of 333 and 336
      amino acids, respectively, with a 97% amino acid identity; LERK-5 has an amino
      acid identity of 27-59% with the other reported LERKs. LERK-5 is a ligand for
      both elk and hek and induces receptor phosphorylation. It is expressed in adult
      lung and kidney and the fetal tissues heart, lung, kidney, and brain. In
      addition, Southern blot analysis of DNA from interspecific backcross mice
      indicated that LERK-5 (Eplg5) maps to the proximal region of mouse chromosome 8.

PMID- 8559145
TI  - Immunodominant RNA recognition motifs of human nucleolin/C23.
AB  - Nucleolin/C23 is a nucleolar phosphoprotein implicated in the synthesis,
      processing and transport of ribosomal RNA and gene transcription. Auto-antibodies
      to human nucleolin/C23 have been reported in patients with systemic lupus
      erythematosus and other systemic autoimmune disorders. To identify immunodominant
      regions in nucleolin/C23, deletion fragments of nucleolin/C23 were fused in frame
      with the glutathione S-transferase gene. Seven monoclonal anti-nucleolin/C23
      antibodies were used to determine the immunoreactivity of the bacterially
      expressed fusion proteins. Two sets of immunogenic regions at amino acids 314-389
      and 387-461 were identified; each contained overlapping discontinuous epitopes
      and a centrally located RNA recognition motif. An auto-immune serum from a
      patient with systemic lupus erythematosus patient was found to contain antibodies
      against human nucleolin/C23 which recognized amino acids 387-461 of
      nucleolin/C23.

PMID- 8559146
TI  - Evidence for an antigen-driven selection process in human autoantibodies against
      acetylcholine receptor.
AB  - Autoantibodies to the nicotinic acetylcholine receptor (AChR) play a central role
      in the neurological symptoms associated with myasthenia gravis (MG). A better
      knowledge of the structural organization and of the mechanisms leading to the
      production of these antibodies may help in understanding the pathogenesis of the
      disease. To achieve this, four IgG anti-AChR monoclonal autoantibodies obtained
      in a previous work were derived from lymphoid cells of MG patients. Two of them
      (MH1 and MH6) were capable of modulating in vitro the expression of AChR at the
      surface of TE-671 cells. We report here the complete nucleotide sequence of the
      heavy and light chains of these four antibodies. Although it is difficult to
      address the issue of VH gene usage in anti-AChR autoantibodies because of the
      limited number of clones studied, our results associated with others which have
      appeared in the literature point to non-stochastic usage by anti-AChR antibody of
      some defined VH genes belonging to VH2 and VH5 minifamilies overexpressed in the
      fetal repertoire. The second and major aim of this work was to assess the role of
      an antigen-driven selection process in the production of anti-AChR
      autoantibodies. When comparing the expressed sequences to their closest germline
      counterparts, it appeared that all four studied clones displayed numerous
      mutations in VH regions. In particular, MH1 and MH6, characterized by their AChR
      modulating capacity, displayed a higher than expected number of mutations and
      replacements occurring in CDR regions. These data point to an antigen-driven
      selection process. On the contrary, the mutational process observed in the MH%
      clone was borderline and that of MH7 was compatible with a random process.
      Interestingly, when comparing mutations in heavy and light chains, a
      significantly lower number of mutations were expressed in light chains for the
      four clones.

PMID- 8559147
TI  - Effects of secondary forces on the primary antibody-ligand interaction.
AB  - The binding efficiency of high affinity monoclonal antifluorescyl antibody 4.4-20
      with the homologous ligand situated in different protein environments has been
      investigated to quantitate the effect of non-active site secondary factors. To
      synthesize monofluoresceinated proteins, fluorescein 5-isothiocyanate was reacted
      with a 100-fold molar excess of ribonuclease, lysozyme, lactalbumin and bovine
      serum albumin. Absorption and emission spectra, as well as fluorescence life-time
      measurements which yielded discrete components and proteolytic studies suggested
      that fluorescein was conjugated to a specific lysine residue consistent with a
      non-random distribution of lysines within each protein population. The
      derivatized residue was probably a surface moiety based on accessibility analyses
      with iodide as a dynamic quencher. Dissociation rate analyses indicated that the
      relative release time of 4.4-20 with each monofluoresceinated protein was Fl
      RNAse > or = Fl-lyso > or = FDS > Fl-lact > or = Fl-BSA which correlated with
      changes in free energy of binding. Relative fluorescence quenching measurements
      of the fluorescein moiety indicated that 4.4-20 showed decreasing quenching in
      the order FDS > Fl-RNAse > Fl-lyso > or = Fl-lact > Fl-BSA. Because spectral data
      indicated that fluorescein was conjugated to a specific residue or a non-random
      distribution of residues in each protein population, the results represented the
      effect of a single distinct environment or a weighted average of different
      microenvironments. Results have been interpreted within the theoretical framework
      of a dynamic antibody model involving conformer selection and the relative
      effects of primary and secondary interactions.

PMID- 8559148
TI  - Characterization of a type II'o group A streptococcal immunoglobulin-binding
      protein.
AB  - The opacity factor positive M type 2 group A streptococcal isolate, A207,
      expresses a unique functional type II'o IgG-binding protein which reacts with all
      four human IgG subclasses and rabbit IgG. In order to determine the gene product
      or products responsible for this activity, three genes of the vir regulon from
      this isolate were cloned, expressed and analysed. The fcr A2 gene coded for a
      protein binding hyman IgG1, IgG2 and IgG4 but not IgG3. The enn2 gene coded for a
      protein reacting exclusively with human IgA, while the emmL2 gene product bound
      IgG1, IgG2, IgG3 and IgG4 as well as rabbit but not horse or pig IgG. The IgG3
      binding activity of the EmmL2 protein was functionally indistinguishable from the
      Form 1 IgG3-binding activity present in heat extracts of group A isolate A207.

PMID- 8559149
TI  - The Fc epsilon RII/CD23 gene is actively transcribed during all stages of murine
      B-lymphocyte development.
AB  - It is generally accepted that the expression of Fc epsilon RII/CD23 on the
      surface of the B-lineage cells is restricted to the stage of the resting, mature
      (sIgM+/sIgD+) B-lymphocyte. However, it is unknown whether activation of the Fc
      epsilon RII/CD23 gene is also restricted to the stage of the mature B-lymphocyte.
      To address this question we investigated a panel of B-lineage cell lines for the
      presence of transcripts encoding Fc epsilon RII/CD23. We detected transcripts in
      16 of 26 B-lineage cell lines representing the entire spectrum of B-cell
      development. In most cases (13 of 16) active transcription of the murine Fc
      epsilon RII/CD23 gene was not coupled with the expression of cell surface Fc
      epsilon RII/CD23 expression did not hold for all murine B-cell lines. One post
      switch B-cell line (sIgM-/sIgG+) expressed Fc epsilon RII/CD23 on the cell
      surface and another could be induced with IL-4 and LPS to express surface Fc
      epsilon RII/CD23. Transcription of the murine CD23 gene in the absence of cell
      surface expression of Fc epsilon RII/CD23 does not appear to simply be an
      aberrant feature of transformed B-cells since we found transcripts, but not
      surface expression, in some normal splenic and peritoneal B-lymphocytes. Our
      findings suggest that the potential for expression of Fc epsilon RII/CD23 may
      occur over a much broader development window of the B-lineage than previously
      suspected. Transcription of the Fc epsilon RII/CD23 gene, in the absence of
      detectable cell surface protein expression in B-lineage cell lines, and in sort
      purified B-lymphocyte subpopulations, implies that in addition to regulatory
      mechanisms already known, murine CD23 is also regulated through post
      transcriptional mechanisms that have not yet been characterized.

PMID- 8559150
TI  - Structural, immunological and functional comparisons of factor H, rheumatoid
      arthritis protein (RHP), and its apparent normal counterpart (N-RHP).
AB  - The isolation and characterization of two human serum proteins, RHP and N-RHP,
      are described. N-RHP appears to be the normal counterpart of RHP which is found
      at elevated levels in sera of patients with rheumatoid arthritis [Rosano et al.
      (1988b) Inflammation 12, 351 - 360]. Although both proteins crossreact with anti
      Factor H and have identical N-terminal amino acid sequences, they differ from
      Factor H in pI, solubility at low ionic strength, and in glycosylation. RHP
      differs from Factor H and N-RHP in antigenicity in the rabbit, in effect on the
      C1q-anti-C1q precipitin reaction, and in ability to disaggregate C1, the first
      component of the complement system. Removal of RHP, N-RHP and Factor H from
      binding to C1q is a prerequesite for separation of RHP and N-RHP from Factor H by
      anion exchange chromatography and isoelectric focusing. The finding of uniquely
      demonstrable RHP activity (enhancement of C1q-anti-C1q precipitin activity) in
      unfractionated sera from patients with rheumatoid arthritis, but not in normal
      sera, suggests that RHP is not an artefact of Factor H produced during isolation.

PMID- 8559151
TI  - The immunogenicity of the 7E3 murine monoclonal Fab antibody fragment variable
      region is dramatically reduced in humans by substitution of human for murine
      constant regions.
AB  - A murine monoclonal antibody (7E3) directed against the platelet glycoprotein
      IIb/IIIa was engineered to reduce immunogenicity by substituting human for murine
      constant regions. The chimeric antibody is functionally identical to the murine
      antibody in vitro. Results from clinical trials with 7E3 Fab antibody fragments,
      however, show that the 7E3 variable region, which elicits the vast majority of
      the immune response to murine 7E3 Fab, is rendered dramatically less immunogenic
      (incidence reduced from 17% to 1%) when the identical variable region is linked
      to human rather than murine constant regions. Neither murine nor human constant
      regions were highly immunogenic themselves. We conclude that the constant regions
      of the Fab fragments are critical in modulating the immune response elicited by
      the linked 7E3 variable region. Because naturally occurring anti-human Fab
      fragment antibodies are prevalent both in the normal human population and in the
      patient population studied here, murine 7E3 Fab and chimeric 7E3 Fab may be
      fundamentally different in their interactions with the human immune system. This
      difference may be related to the dramatic difference in immunogenicity observed
      between murine 7E3 Fab and chimeric 7E3 Fab.

PMID- 8559152
TI  - Manipulation of B cell antigen receptor tyrosine phosphorylation using aluminum
      fluoride and sodium orthovanadate.
AB  - The B cell antigen receptor complex (BCR) is composed of a membrane-spanning
      immunoglobulin molecule (mIg) non-covalently associated with heterodimers of the
      transmembrane proteins Ig-alpha and Ig-beta. The cytoplasmic domains of Ig-alpha
      and Ig-beta do not contain kinase domains but are phosphorylated on tyrosine
      residues immediately upon receptor ligation. The mechanism and kinase responsible
      for initial Ig-alpha and Ig-beta phosphorylation following receptor ligation is
      unknown, In an attempt to better understand this process, Ig-alpha and Ig-beta
      phosphorylation was examined in response to treatment of permeabilized B cells
      with the pharmacologic agents, aluminum fluoride (AlFx) and sodium orthovanadate
      (Na3VO4). AlFx is known to stimulate GTP-binding proteins while Na3VO4 inhibits
      protein tyrosine phosphatases (PTPs), both of which are involved in the BCR
      signalling cascade. In these studies, AlFx and Na3VO4 stimulated rapid tyrosine
      phosphorylation of Ig-alpha, Ig-beta, and additional cellular proteins, including
      the protein tyrosine kinase (PTK) Lyn. The tyrosine phosphorylation does not
      appear to be mediated through GTP-binding proteins, since GTP gamma S did not
      stimulate tyrosine phosphorylation. As expected, however, PTPs modulate the
      phosphorylation state of these proteins since another PTP inhibitor, phenylarsine
      oxide (PAO), increased phosphorylation of Ig-alpha, Ig-beta and other proteins in
      this system. Interestingly, the extent and kinetics of the mIg-associated Lyn and
      Ig-alpha/Ig-beta phosphorylation was correlated, suggesting that Lyn may mediate
      receptor phosphorylation. Alternatively, Lyn, may be a downstream effector of
      phosphorylated Ig-alpha and Ig-beta as suggested by the reported ability of
      biphosphorylated Ig-alpha to activate Fyn PTK in vitro. Finally, all components
      necessary for Na3VO4, but not AlFx, stimulation of phosphorylation are membrane
      associated. The data are consistent with modulation of phosphorylation of Ig
      alpha and Ig-beta through both PTP inhibition and AlFx treatment, and a common
      intermediary in or effector of these phosphorylation pathways appears to be the
      Lyn kinase.

PMID- 8559153
TI  - Pep34, a synthetic peptide whose sequence corresponds to the intracytoplasmic
      domain of the Epstein-Barr virus receptor (CR2, CD21), regulates human B
      lymphocyte proliferation triggered through CR2.
AB  - CR2 is involved in regulation of human B lymphocyte proliferation by interacting,
      through distinct domains, with extracellular, cell surface or intracellular
      components. Contribution of CR2 intracytoplasmic domain in CR2 regulatory
      functions remains unclear. Thus, we used pep34, a 34 amino acid synthetic peptide
      whose sequence corresponds to CR2 intracytoplasmic domain. Pep34 was incorporated
      into B lymphocytes which were then activated by EBV or C3d through CR2. Our data
      demonstrate that pep34 inhibits 100% B lymphocyte proliferation triggered by EBV
      or C3d. Irrelevant peptide had no effect. When B lymphocyte proliferation was
      triggered by a multipotent B cell activator as SAC, pep34 did not exert any
      inhibitory effect. Our data demonstrate that pep34 inhibits B lymphocyte
      proliferation only when lymphocytes are triggered through CR2. Thus, this
      strongly supports that despite its short length. CR2 intracytoplasmic domain
      participates to regulatory functions of this receptor.

PMID- 8559154
TI  - Is it easier to use a secure mother as a secure base? Attachment Q-sort
      correlates of the adult attachment interview.

PMID- 8559155
TI  - The role of parenting sensitivity, infant temperament, and dyadic interaction in
      attachment theory and assessment.

PMID- 8559156
TI  - Attachment security, affect regulation, and defensive responses to mood
      induction.

PMID- 8559157
TI  - The prototype hypothesis and the origins of attachment working models: adult
      relationships with parents and romantic partners.

PMID- 8559158
TI  - A quantitative approach to the description and classification of primary social
      relationships.

PMID- 8559159
TI  - Reciprocal change of motor evoked potentials preceding voluntary movement in
      humans.
AB  - Reciprocal change of motor evoked potentials (MEPs) recorded from the agonist and
      antagonist muscles of the forearm was studied in 10 normal subjects in whom
      transcranial magnetic stimulation (TMS) was applied to the hand motor area before
      voluntary wrist movements. MEP recorded from the agonist muscles, that is, radial
      extensor muscles for wrist extension and ulnar flexor muscle for wrist flexion,
      were gradually facilitated with shortening of the interval between the magnetic
      stimulation and the voluntary muscle contraction. In contrast, MEP recorded from
      the antagonist muscles, that is, ulnar flexor muscle for wrist extension and
      radial extensor muscles for wrist flexion, were gradually suppressed as the
      interval shortened. The reciprocal change of MEP was recognized when TMS was
      applied within 60 ms prior to the voluntary movements. The present data confirmed
      that reciprocal change of MEP was recognized before voluntary movements; they
      further suggest that cortically originated reciprocal control of the
      corticospinal pathway may exist and that it may be generated just before the
      voluntary movement.

PMID- 8559160
TI  - Yields of muscle from myogenic cells implanted into young and old mdx hosts.
AB  - Implantation of normal muscle precursor cells (mpc) for treatment for inherited
      myopathies such as Duchenne muscular dystrophy is in clear need of improvement to
      become practicable, but few variables have been studied comparatively. Here, we
      report the first quantitative estimate of the effectiveness of implanting mpc
      into preirradiated muscles of young and old mice and into preirradiated and
      nonirradiated old muscles. Estimates were made of the amount of muscle formed by
      injection of 5 x 10(5) cells dissociated from neonatal normal mouse muscle into
      tibialis anterior muscles of the dystrophin-deficient mdx mouse. We show that
      normal mpc are incorporated slightly more efficiently into muscles of young than
      old host mice, to form some 10 mg of dystrophin-positive fibers. In older
      muscles, prior irradiation has little effect on the total yield of new muscle.

PMID- 8559161
TI  - Frequency of median mononeuropathy in patients with mild diabetic neuropathy in
      the early diabetes intervention trial (EDIT). Tolrestat Study Group For Edit
      (Early Diabetes Intervention Trial)
AB  - We used electrophysiologic criteria to identify median mononeuropathy (MM) at the
      nondominant wrist among 414 patients enrolled in a multicenter study of patients
      with mild diabetic neuropathy according to consensus recommendations. Patients
      with absent sural or peroneal responses or greater than mild symptoms of carpal
      tunnel syndrome were ineligible. Ninety-five of 414 participants (23%) fulfilled
      criteria for MM, independent of diabetes type. Patients with MM had a longer
      duration of diabetes than remaining patients, independent of age, and patients
      with MM and type II diabetes were more likely to be female (34% vs. 19%; P =
      0.008), shorter (165.7 vs. 172.7 cm; P = 0.001), and have a higher body mass
      index (32.5 vs. 29.1; P = 0.0008) than remaining type II patients. Sural or
      peroneal conduction abnormalities did not influence the frequency of MM. These
      results suggest that patients with diabetic neuropathy require special
      consideration with regard to the evaluation of suspected carpel tunnel syndrome.

PMID- 8559162
TI  - Tenascin-C expression in dystrophin-related muscular dystrophy.
AB  - The mdx mouse has a mutated dystrophin gene and is used as a model for the study
      of Duchenne muscular dystrophy (DMD). We investigated whether regenerating mdx
      skeletal muscle contains the extracellular matrix protein tenascin-C (TN-C),
      which is expressed in wound healing and nerve regeneration. Prior to the
      initiation of muscle degeneration, both normal and mdx mice displayed similar
      weak staining for TN-C in skeletal muscle, but by 3 weeks of age the mice
      differed substantially. TN-C was undetectable in normal muscle except at the
      myotendinous junction, while in dystrophic muscle, TN-C was prominent in
      degenerating/regenerating areas, but absent from undegenerated muscle. With
      increasing age, TN-C staining declined around stable regenerated mdx myofibers.
      TN-C was also observed in muscle from dogs with muscular dystrophy and in human
      boys with DMD. Therefore, in dystrophic muscle, TN-C expression may be stimulated
      by the degenerative process and remain upregulated unless the tissue undergoes
      successful regeneration.

PMID- 8559163
TI  - Electrophysiological pattern of involuntary limb movements in the restless legs
      syndrome.
AB  - Patients with restless legs syndrome (RLS) suffer from involuntary limb movements
      during the day. We studied these leg movements in 18 idiopathic (n = 8) and
      uremic (n = 10) patients at rest. Electromyographically measured muscle
      contractions were preceded by sensory discomfort in all patients. The mean
      duration of the contractions ranged between 0.67 and 5.71 s with a mean frequency
      of 244 epochs of muscle activity per hour. Seven of 18 patients showed a constant
      order of recruitment with propagation of muscle activity up or down spinal
      segments (L3 to S1 and vice versa). No difference in electrophysiologically
      recorded patterns was observed between patients with idiopathic and uremic RLS.
      We suggest a brainstem disinhibition phenomenon as the pathological mechanism
      that activates a spinal generator. The spinal origin of the involuntary limb
      movements in patients with RLS is confirmed by the long duration of jerks, the
      recruitment characteristics, and the periodicity of the jerks. No jerk could be
      elicited by sensory reflexes.

PMID- 8559164
TI  - Hypertrophic neuritis due to chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP): a postmortem pathological study.
AB  - A postmortem pathological study of a 65-year-old woman with hypertrophic neuritis
      associated with hand tremor and limb ataxia is described. There were many onion
      bulbs and loss of myelinated nerve fibers in the peripheral nerves, including the
      facial and subserosal visceral nerves. The hypertrophic neuritis was caused by
      chronic inflammatory demyelinating neuropathy (CIDP), in which interstitial
      amorphous substances in the endoneurium and onion bulb formation might contribute
      to nerve swelling. We speculate that visceral autonomic nerves as well as somatic
      peripheral nerves are involved in patients with a long clinical CIDP course and
      that peripheral nerve pathology in this disorder shows more heterogeneous changes
      than previously recognized.

PMID- 8559165
TI  - Lumbrical-interossei motor studies localize ulnar neuropathy at the wrist.
AB  - Ulnar nerve entrapment at the wrist (UNW) is uncommon and often difficult to
      localize electrophysiologically. The difference between the motor latencies to
      the median-innervated second lumbrical (2L) and ulnar-innervated palmar
      interosseous (Pl) (Diff 2L-Pl) has been shown to be of localizing value in
      patients with median neuropathy at the wrist. In the last year, we evaluated 2
      patients with clinically definite ulnar neuropathy at the wrist. We performed
      motor studies to the 2L-Pl on the 2 patients and 12 disease controls with ulnar
      neuropathy at the elbow as follows: Using the same electrodes to record both the
      2L and Pl, the median and ulnar nerves were each stimulated supramaximally above
      the wrist using identical distances. In the disease control subjects, the Diff 2L
      Pl was essentially the same as normal controls (mean [0.13], range [(-0.3)-0.4]).
      In both patients with UNW, the Diff 2L-Pl clearly supported the routine
      electrophysiological studies in localizing the lesion (ulnar latencies were 1.1
      and 1.8 ms longer than the median latencies). We conclude that the lumbrical
      interosseous latency difference is useful in localizing ulnar nerve entrapment to
      the wrist.

PMID- 8559167
TI  - Current perception thresholds in toe-to-digit transplantation and digit-to-digit
      replantation.
AB  - Recovery of digital nerve function in toe-to-digit transplantation and digit-to
      digit replantation was evaluated by transcutaneous constant current sine wave
      stimulation at 5-, 250-, and 2000-Hz frequencies to determine the current
      perception thresholds (CPT). For toe transplantation and digit replantation, the
      mean interval between injury and surgery was 9 months and 7 h, respectively,
      while the mean interval between surgery and CPT study was 52 months and 20
      months, respectively. Control CPTs evoked by three frequency stimuli were
      obtained from contralateral corresponding normal finger and normal toe. Normal
      finger had significantly lower 250- and 2000-Hz CPTs than normal toe, but the 5
      Hz CPT was not different between them. Replanted digit achieved nearly complete
      recovery of these three frequency CPTs when compared to normal finger. In toe
      transplantation, 2000-Hz CPT was comparable to normal finger, while 5- and 250-Hz
      CPTs were comparable to normal toe. The present findings suggest that the
      transplanted toe was intermediate between normal finger and normal toe, but more
      like normal toe than normal finger with regard to detection thresholds of the
      current-evoked sensation.

PMID- 8559166
TI  - Localization and amount of myoglobin and myoglobin mRNA in ragged-red fiber of
      patients with mitochondrial encephalomyopathy.
AB  - The localization and amounts of myoglobin (Mb) and Mb mRNA in ragged-red fibers
      (RRF) in skeletal muscle of 6 patients with mitochondrial encephalomyopathy were
      examined immunohistochemically and by in situ hybridization. The amounts of Mb
      and Mb mRNA were expressed in terms of optical densities (ODs) of Mb
      immunostaining and Mb mRNA signals. In nonatrophic RRF, Mb was predominantly seen
      in the ragged-red region and Mb mRNA signals were increased throughout the
      sarcoplasm. The amounts of Mb and Mb mRNA in nonatrophic RRF were greater than
      those in nonatrophic non-RRF. In contrast, the localization and amount in
      atrophic RRF were similar to those in atrophic non-RRF. Thus, Mb synthesis in
      nonatrophic RRF may increase to compensate for mitochondrial dysfunction and to
      supply sufficient oxygen to mitochondria, but this compensatory function may be
      impaired in atrophic RRF.

PMID- 8559168
TI  - Sporadic MERRF/MELAS overlap syndrome associated with the 3243 tRNA(Leu(UUR))
      mutation of mitochondrial DNA.
AB  - We studied a patient with a mitochondrial encephalomyopathy characterized by the
      presence of all the cardinal features of both myoclonic epilepsy and ragged-red
      fibers (MERRF) and mitochondrial encephalomyopathy, lactic acidosis, and
      strokelike episodes (MELAS) syndromes. Muscle biopsy showed ragged-red fibers
      (RRF). Some RRF were cytochrome c oxidase (COX)-negative while some others
      stained positive for COX. Muscle biochemistry revealed defects of complexes I and
      IV of the respiratory chain. Both muscle and blood mitochondrial DNA from the
      patient showed the presence of the mutation at nucleotide position 3243 in the
      tRNA(Leu(UUR)) gene and the absence of point mutations related to MERRF syndrome.
      The proportions of mutant mtDNA were 70% in muscle and 30% in blood. The mutation
      was absent in blood from all maternal relatives, in hair follicles from the
      mother, and in muscle from one sister of the proband. Therefore, there was no
      evidence of maternal inheritance.

PMID- 8559169
TI  - Somatosensory evoked potentials during the ideation and execution of individual
      finger movements.
AB  - Scalp somatosensory evoked potentials (SEPs) were recorded in 10 volunteers after
      median nerve stimulation, in four experimental conditions of hand movements
      performance/ideation, and compared with the baseline condition of full
      relaxation. The experimental conditions were (a) self-improvised hand-finger
      sequential movements; (b) the same movements according to a read sequence of
      numbers; (c) mental ideation of finger movements; and (d) passive displacement of
      fingers in complete relaxation. Latencies and amplitudes of the parietal (N20,
      P25, N33, and P45) and frontal peaks (P20-22, N30, and P40) were analyzed.
      Latencies did not vary in any of the paradigms. Among the parietal complexes,
      only the P25-N33 amplitude was significantly reduced in (a), (b), (c), and (d)
      and the N20-P25 was reduced in (a) and (d); among frontal waves, N30 and P40 were
      significantly reduced (20-75%) in (a) and (b). Coronal electrodes showed
      amplitude decrements maximal at the frontal-rolandic positions contralateral to
      the stimulated side.

PMID- 8559170
TI  - Efficacy of limb cooling on the salvage of peripheral nerve from ischemic fiber
      degeneration.
AB  - Since peripheral nerve has a large ischemic safety factor, hypothermia, by
      reducing metabolic demands, is potentially an efficacious technique to rescue
      nerve from ischemic fiber degeneration (IFD). We therefore evaluated the
      influence of temperature on the severity of IFD resulting from a standard
      ischemic stress. Ischemia to the left sciatic nerve in the rat was produced by
      embolization of 2 x 10(6) microspheres (14 microns) into its supplying arteries.
      The limb was embolized at three temperatures, 37 degrees C, 32 degrees C, and 28
      degrees C and was maintained at each temperature for an additional 4 h. End
      points, evaluated 7 days after embolization, for the embolized limb were: (1)
      behavioral scores, 0-11 in increasing limb function; (2) compound nerve action
      potential of sciatic-tibial nerve; (3) sciatic nerve blood flow (NBF, in mL/100
      g/min); and (4) histologic grade, expressed as percentage of fibers undergoing
      IFD (0 = < 5%; 1 = 5-25%; 2 = 26-50%; 3 = 51-75%; 4 = > 75%). NBF was reduced in
      all groups, varying with temperature, and all indices of nerve structure and
      function were significantly improved with hypothermia. We conclude that
      hypothermia, easily achievable in a limb nerve, is highly efficacious in the
      rescue of nerve from IFD. These findings are of clinical relevance.

PMID- 8559171
TI  - Isaacs' syndrome associated with chronic inflammatory demyelinating
      polyneuropathy.
AB  - We report the first case of Isaacs' syndrome in which an inflammatory
      demyelinating neuropathy was documented histologically. For 9 months, the patient
      developed slowly progressive weakness, muscle spasms and stiffness,
      fasciculations, and myokymia in the arms, which were unmodified by sleep. Nerve
      conduction studies showed multifocal motor conduction block, abnormal dispersion
      phenomenon, and abnormal sensory and mixed nerve conduction. Needle
      electromyogram showed continuous motor unit potentials at rest with bursts of
      rapid-firing discharges which were unaffected by spinal anesthesia but diminished
      by peripheral nerve block and completely abolished by local curarization. Sural
      nerve biopsy demonstrated an inflammatory demyelinating neuropathy. Muscle
      cramping, twitching, and stiffness responded to phenytoin. The patient's weakness
      gradually responded to prednisone and azathioprine. Over a 17-year period, the
      patient had three relapses which were well controlled with prednisone and
      azathioprine. At this time, the patient is symptom-free without any medication.

PMID- 8559172
TI  - Are fibrillation potentials and positive sharp waves the same? No.
AB  - Electrodiagnostic medicine consultants report electrical activity in muscle
      recorded at rest and during voluntary movement by means of waveform and firing
      rate characteristics. This principle allows us to distinguish fibrillation
      potentials from positive sharp waves. Although in most cases these two potentials
      have the same clinical significance, there are at least five different situations
      in which they do not have an identical meaning: (1) positive sharp waves can be
      recorded earlier after a peripheral nerve injury than can fibrillation
      potentials; (2) occasionally, nonclinically significant diffuse positive sharp
      wave activity may be seen in the absence of fibrillation activity (i.e., "EMG
      disease"); (3) positive sharp waves may be seen in distal muscles of "normal"
      subjects without the presence of fibrillation activity or clinical significance;
      (4) positive sharp waves without fibrillation potentials may be seen following
      local muscle trauma; and (5) positive sharp waves may be seen alone in some
      demyelinating polyneuropathies. By accurately describing the observed potentials,
      the electrodiagnostic medicine consultant may be able to obtain more clinically
      useful information from an electrodiagnostic study.

PMID- 8559173
TI  - Single muscle fiber discharges (insertional activity, end-plate potentials,
      positive sharp waves, and fibrillation potentials): a unifying proposal.
AB  - The exact origin and precise morphologic explanation of positive sharp waves
      (PSWs) are presently lacking. Observing normal needle electromyographic
      insertional activity reveals two types of waveforms: (1) biphasic
      negative/positive spikes, and (2) positive spikes followed by a small negative
      phase. In the end-plate region, it is possible to occasionally observe a biphasic
      end-plate spike transform into a monophasic positive end-plate waveform. It is
      postulated that this waveform is simply a form of intracellular recording for the
      biphasic end-plate spike or a form of extracellularly recorded but blocked single
      muscle fiber discharge. Similarly, the observed monophasic positive insertional
      activity may be an intracellularly recorded single muscle fiber discharge or a
      blocked extracellular discharge originating about the needle electrode. Applying
      this reasoning to PSWs suggests that they may also be an intracellular recording
      of a fibrillation potential, or needle-induced extracellular blocked local single
      muscle fiber discharge. This unifying concept is applied to various clinical
      situations purported to demonstrate "different" types of PSWs.

PMID- 8559174
TI  - Combined motor and sensory median-ulnar anastomosis: report of an
      electrophysiologically proven case.

PMID- 8559175
TI  - Mononeuropathy multiplex associated with celiac sprue.

PMID- 8559176
TI  - Severe carpal tunnel syndrome: clinical and electrodiagnostic outcome of surgical
      and conservative treatment.

PMID- 8559177
TI  - (CTG)n expansions in various tissues from a myotonic dystrophy patient.

PMID- 8559178
TI  - Value of latency measurements to the small palm muscles compared to other
      conduction parameters in the carpal tunnel syndrome.

PMID- 8559179
TI  - Facial myokymia: segmental demyelination demonstrated by magnetic stimulation.

PMID- 8559180
TI  - Plexiform neurofibroma of the cauda equina presenting as peroneal muscular
      atrophy.

PMID- 8559181
TI  - Thoracic outlet syndrome.

PMID- 8559182
TI  - Trigger points related to calcium channel blockers.

PMID- 8559183
TI  - How often are preoperative electrodiagnostic studies obtained for carpal tunnel
      syndrome in a Medicaid population?

PMID- 8559184
TI  - Infection by Mycoplasma pneumoniae induces serum antibody against Gal-C.

PMID- 8559185
TI  - Prolonged latency to 2nd lumbrical signifying an incipient carpal tunnel
      syndrome: a case report.

PMID- 8559186
TI  - New systematically active antimycotics from the beta-blocker category.
AB  - Candida albicans secretes phospholipases, which are considered to be one of the
      mediators of cell penetration. It is known that other phospholipases from
      mammalian cells can be inhibited by lipophilic beta-blocking structures. As the
      result of a synthesis programme of several years' duration, structures deriving
      from beta-hydroxyethylamines were introduced. In vitro and in vivo results with
      these compounds are presented in comparison with standard antimycotics. In
      combination with fluconazole, several of the compounds can prevent death in mice
      infected with lethal inocula of C. albicans. Histological examinations confirm
      the inhibitory effect of the beta-blocker-like structures on tissue penetration.
      The structures therefore constitute new antimycotics that are endowed with
      extensive in vitro effectiveness against fungi and also definite in vivo effects
      in the animal model.

PMID- 8559187
TI  - Growth of Candida albicans in normal and altered faecal flora in the model of
      continuous flow culture.
AB  - We used the model of faecal microflora under continuous flow culture (CFC)
      conditions to study the growth of Candida albicans in mixed cultures. The
      development of Candida is usually limited by the high germ counts of aerobic and
      anaerobic bacteria. Candida growth in faecal flora could be obtained neither by
      the continuous inflow of C. albicans CFC monocultures nor by intermittent input
      of highly concentrated suspensions of C. albicans into the system. If the system
      was run under aerobic conditions development of C. albicans could be observed.
      After some days, however, the faecal flora again suppressed further development
      of the yeasts. Only marked destruction of the aerobic and anaerobic microflora by
      antibiotics resulted in growth or overgrowth of Candida albicans.

PMID- 8559188
TI  - Mycetoma due to Exophiala jeanselmei and Mycobacterium chelonae in a 73-year-old
      man with idiopathic CD4+ T lymphocytopenia.
AB  - Exophiala jeanselmei and Mycobacterium chelonae were isolated from cutaneous
      nodules in a 73-year-old man with mycetoma of the right lower leg. Further
      evaluation revealed CD4+ lymphocytopenia without evidence of HIV infection.
      Antibodies to HIV 1/2, p24 antigen and HIV 1/2 (PCR) and reverse transcriptase
      activity were not detectable. The patient was not a member of any HIV risk group.
      He had not previously undergone therapy or suffered from immunodeficiency. This
      case clearly demonstrates that infections with opportunistic moulds and/or
      atypical mycobacteria should be taken into consideration not only in patients
      with classical immundeficiency diseases but also in apparently healthy patients
      because infection with these agents can be the first sign of underlying
      immunodeficiency.

PMID- 8559189
TI  - Fluconazole in the treatment of pulmonary zygomycosis.
AB  - Pulmonary zygomycosis is an aggressive, often terminal infection that may be
      found in patients who are immunocompromised as a result of cytotoxic
      chemotherapy. Conventional treatment is by surgical debridement augmented with
      high-dose intravenous amphotericin B, but even with such treatment the course is
      usually fulminant with a high mortality rate. Recent work has suggested that the
      new antifungal triazole, fluconazole, may be of benefit in treating zygomycete
      infection. The case of a 15-year-old boy who developed pulmonary zygomycosis
      while on chemotherapy for acute lymphoblastic leukaemia, and who survived for 11
      months with oral fluconazole therapy alone, is supportive of this proposal.

PMID- 8559190
TI  - Mixed intranasal infection caused by Fusarium solani and a zygomycete in a
      leukaemic patient.
AB  - We report a case of mixed intranasal infection caused by Fusarium solani and a
      zygomycete, with probable sinus and brain involvement. The patient had chronic
      myelogenous leukaemia and was treated with chemotherapy. Diagnosis of the
      infection was established by direct examination of the intranasal eschar and
      histopathological study of an excisional biopsy. Only F. solani was isolated from
      both specimens. Difficulties in diagnosis and treatment of these infections are
      discussed.

PMID- 8559191
TI  - Successful treatment of cutaneous sporotrichosis with liquid nitrogen: report of
      three cases.
AB  - Sporotrichosis is a not uncommon deep fungal infection that frequently involves
      the skin. At present, there are several therapeutic modalities available to treat
      this infection. This report outlines the successful treatment of three cases of
      sporotrichosis using liquid nitrogen. Cryotherapy may be useful in treating some
      cases of this disease.

PMID- 8559192
TI  - The yeast spectrum of the 'tea fungus Kombucha'.
AB  - The tea fungus 'Kombucha' is a symbiosis of Acetobacter, including Acetobacter
      xylinum as a characteristic species, and various yeasts. A characteristic yeast
      species or genus has not yet been identified. Kombucha is mainly cultivated in
      sugared black tea to produce a slightly acidulous effervescent beverage that is
      said to have several curative effects. In addition to sugar, the beverage
      contains small amounts of alcohol and various acids, including acetic acid,
      gluconic acid and lactic acid, as well as some antibiotic substances. To
      characterize the yeast spectrum with special consideration given to facultatively
      pathogenic yeasts, two commercially available specimens of tea fungus and 32 from
      private households in Germany were analysed by micromorphological and biochemical
      methods. Yeasts of the genera Brettanomyces, Zygosaccharomyces and Saccharomyces
      were identified in 56%, 29% and 26% respectively. The species Saccharomycodes
      ludwigii and Candida kefyr were only demonstrated in isolated cases. Furthermore,
      the tests revealed pellicle-forming yeasts such as Candida krusei or Issatchenkia
      orientalis/occidentalis as well as species of the apiculatus yeasts (Kloeckera,
      Hanseniaspora). Thus, the genus Brettanomyces may be a typical group of yeasts
      that are especially adapted to the environment of the tea fungus. However, to
      investigate further the beneficial effects of tea fungus, a spectrum of the other
      typical genera must be defined. Only three specimens showed definite
      contaminations. In one case, no yeasts could be isolated because of massive
      contamination with Penicillium spp. In the remaining two samples (from one
      household), Candida albicans was demonstrated. The low rate of contamination
      might be explained by protective mechanisms, such as formation of organic acids
      and antibiotic substances. Thus, subjects with a healthy metabolism do not need
      to be advised against cultivating Kombucha. However, those suffering from
      immunosuppression should preferably consume controlled commercial Kombucha
      beverages.

PMID- 8559193
TI  - Chronic bilateral suppurative otitis media caused by Aspergillus terreus.
AB  - A case of bilateral suppurative otitis media is described in a patient with the
      presenting symptoms of otorrhoea, itching, mild deafness, heaviness in the ear
      and otalgia. The patient had perforation in the tympanic membrane. Histological
      sections revealed aggregated fungal masses of Aspergillus terreus. The infection
      responded well to topical ketoconazole therapy. Incidentally, this is the second
      case from India of chronic suppurative otitis media caused by fungi.

PMID- 8559194
TI  - Two cases of cutaneous phaeohyphomycosis caused by Curvularia pallescens.
AB  - Two cases of cutaneous phaeohyphomycosis caused by Curvularia pallescens are
      described. Lesions were found on the feet, thigh and thumb and were irregularly
      marginated, pruritic black and occasionally purulent. Histopathology revealed
      heavy infection of the stratum corneum and other cutaneous layers as well as host
      tissue response. The fungus appeared as dark, aggregated to simple branched
      hyphae. Oxiconazole was most effective 'in vitro' against the pathogen. This is
      the first report of C. pallescens as an opportunistic pathogen of human skin.

PMID- 8559195
TI  - In vitro antifungal activity of Polyporaceae against yeasts and dermatophytes.
AB  - The antifungal activity of 38 Polyporaceae sensu lato against yeasts and
      dermatophytes was tested in vitro by the agar dilution method. Strains were typed
      organisms and clinical isolates. In this first report, Pycnoporellus fulgens
      (Fr.) Donk was found to be the most active species against pathological fungi and
      showed broad-spectrum antifungal activity against yeasts (Candida albicans,
      Candida glabrata) and dermatophytes (Trichophyton mentagrophytes, Trichophyton
      rubrum, Microsporum canis, Microsporum gypseum, Epidermophyton floccosum). Other
      Polyporaceae species also showed antifungal activity, but only against
      dermatophytes.

PMID- 8559196
TI  - Preliminary screening of some squalenoid derivatives for toxicity towards
      dermatophytes.
AB  - We report a preliminary study of the in vitro anti-dermatophyte activity of six
      squalenoid derivatives that inhibit 2,3-oxidosqualene cyclase and squalene
      epoxidase: 2-aza-2,3-dihydrosqualene, 22,23-epoxy-2-aza-2,3-dihydrosqualene,
      azasqualene alcohol, 19-aza-18,19,22,23-tetrahydrosqualene, 2,3-epoxy-19-aza
      18,19,22,23-tetrahydrosqualene and hexafluorosqualene epoxide. The tests were
      done by inoculating 10 microliters of Trichophyton mentagrophytes (Robin)
      Blanchard or Microsporum canis Bodin homogenate into 1 ml of Sabouraud glucose
      liquid medium containing serial dilutions from 100 to 0.25 micrograms ml-1 of the
      substance. For each compound the minimum inhibitory concentration (MIC) and the
      minimum fungicidal concentration (MFC) were determined. The most effective
      compounds were 22,23-epoxy-2-aza-2,3-dihydrosqualene and azasqualene alcohol,
      with MICs respectively of 3 and 6.25 micrograms ml-1 for each of the two species
      of dermatophyte. The first of these compounds was the only one to show fungicidal
      activity over the range of concentrations tested.

PMID- 8559197
TI  - Topical treatment of tinea corporis and tinea cruris with eberconazole (WAS 2160)
      cream 1% and 2%: a phase II dose-finding pilot study.
AB  - In a phase II pilot dose-finding study 60 patients with mycologically proven
      tinea corporis and tinea cruris were treated with eberconazole cream 1% once
      daily (group A, 15 patients), 1% twice daily (group B, 15 patients), 2% once
      daily (group C, 15 patients) or 2% twice daily (group D, 15 patients). Treatment
      was continued for 2 weeks after clinical cure; the maximum duration of treatment
      was limited to 6 weeks. The characteristics of the four groups of patients,
      distribution of the target lesions, clinical sum of baseline scores and infecting
      organisms were similar. Statistical examination showed that the mean time of
      appearance in weeks of negative microscopy and culture was similar in the four
      groups. There was no significant difference between the groups in terms of the
      range and mean duration of treatment. By the end of the study, treatment was
      effective in 13 patients (87%) in group A, 14 (93%) in group B and 11 (73%) in
      both groups C and D (mycological cure and clinical cure or residual minimal signs
      and symptoms). One patient in group A did not respond to treatment and two
      patients in group C had to withdraw because of side-effects. No undesirable
      effects or significant changes were seen in the blood tests. At the assessment 6
      weeks post therapy, eberconazole was judged to have been effective in 93% of
      patients in group A, 100% of patients in groups B and D and 61% of patients in
      group C. Although not statistically significant, a trend towards more favourable
      results was seen in group B when considering the mean time of appearance of
      clinical cure and negative KOH and culture.

PMID- 8559198
TI  - Tinea capitis in the Florence area between 1985 and 1993.
AB  - This paper describes the main epidemiological findings in 203 patients with tinea
      capitis and in seven other patients with dermatophytosis that had also extended
      to the scalp. The patients were observed over a 9-year period (from 1985 to 1993)
      at the Department of Dermatology of the University of Florence. Tinea capitis was
      the fourth most frequent dermatophytosis. Most of the patients were children,
      although 23 were adults. The most frequent aetiological agent was Microsporum
      canis. It is interesting to note that there were 12 cases of tinea capitis due to
      Trichophyton violaceum in African immigrants. This dermatophyte was believed to
      have disappeared from Italy. One case was due to Epidermophyton floccosum.

PMID- 8559199
TI  - Tinea capitis in adults.
AB  - Invasion of keratin of the hair by dermatophytes is a rare event after puberty. A
      study of 2200 patients affected by various mycotic cutaneous infections during 6
      years of observation brought to our attention three cases of tinea capitis in
      adults. Confirming the studies of other authors, we also found that this disease
      mostly affected females. In all cases the isolated aetiological agent was
      Microsporum canis, the fungus species most frequently responsible for tinea
      capitis in Italy.

PMID- 8559200
TI  - Electrocardiographic diagnosis of evolving acute myocardial infarction in the
      presence of left bundle-branch block. GUSTO-1 (Global Utilization of
      Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)
      Investigators.
AB  - BACKGROUND: The presence of left bundle-branch block on the electrocardiogram may
      conceal the changes of acute myocardial infarction, which can delay both its
      recognition and treatment. We tested electrocardiographic criteria for the
      diagnosis of acute infarction in the presence of left bundle-branch block.
      METHODS: The base-line electrocardiograms of patients enrolled in the GUSTO-1
      (Global Utilization of Streptokinase and Tissue Plasminogen Activator for
      Occluded Coronary Arteries) trial who had left bundle-branch block and acute
      myocardial infarction confirmed by enzyme studies were blindly compared with the
      electrocardiograms of control patients who had chronic coronary artery disease
      and left bundle-branch block. The electrocardiographic criteria for the diagnosis
      of infarction were then tested in an independent sample of patients presenting
      with acute chest pain and left bundle-branch block. RESULTS: Of 26,003 North
      American patients, 131 (0.5 percent) with acute myocardial infarction had left
      bundle-branch block. The three electrocardiographic criteria with independent
      value in the diagnosis of acute infarction in these patients were an ST-segment
      elevation of 1 mm or more that was concordant with (in the same direction as) the
      QRS complex; ST-segment depression of 1 mm or more in lead V1, V2, or V3; and ST
      segment elevation of 5 mm or more that was disconcordant with (in the opposite
      direction from) the QRS complex. We used these three criteria in a multivariate
      model to develop a scoring system (0 to 10), which allowed a highly specific
      diagnosis of acute myocardial infarction to be made. CONCLUSIONS: We developed
      and validated a clinical prediction rule based on a set of electrocardiographic
      criteria for the diagnosis of acute myocardial infarction in patients with chest
      pain and left bundle-branch block. The use of these criteria, which are based on
      simple ST-segment changes, may help identify patients with acute myocardial
      infarction, who can then receive appropriate treatment.

PMID- 8559201
TI  - Efficacy of pamidronate in reducing skeletal events in patients with advanced
      multiple myeloma. Myeloma Aredia Study Group.
AB  - BACKGROUND: Skeletal complications are a major clinical manifestation of multiple
      myeloma. These complications are caused by soluble factors that stimulate
      osteoclasts to resorb bone. Bisphosphonates such as pamidronate inhibit
      osteoclastic activity and reduce bone resorption. METHODS: Patients with stage
      III multiple myeloma and at least one lytic lesion received either placebo or
      pamidronate (90 mg) as a four-hour intravenous infusion given every four weeks
      for nine cycles in addition to antimyeloma therapy. The patients were stratified
      according to whether they were receiving first-line (stratum 1) or second-line
      (stratum 2) antimyeloma chemotherapy at entry into the study. Skeletal events
      (pathologic fracture, irradiation of or surgery on bone, and spinal cord
      compression), hypercalcemia (symptoms or a serum calcium concentration > or = 12
      mg per deciliter [3.0 mmol per liter]), bone pain, analgesic-drug use,
      performance status, and quality of life were assessed monthly. RESULTS: Among 392
      treated patients, the efficacy of treatment could be evaluated in 196 who
      received pamidronate and 181 who received placebo. The proportion of patients who
      had any skeletal events was significantly lower in the pamidronate group (24
      percent) than in the placebo group (41 percent, P < 0.001), and the reduction was
      evident in both stratum 1 (P = 0.04) and stratum 2 (P = 0.004). The patients who
      received pamidronate had significant decreases in bone pain and no deterioration
      in performance status and quality of life. Pamidronate was tolerated well.
      CONCLUSIONS: Monthly infusions of pamidronate provide significant protection
      against skeletal complications and improve the quality of life of patients with
      stage III multiple myeloma.

PMID- 8559202
TI  - A reversible posterior leukoencephalopathy syndrome.
AB  - BACKGROUND AND METHODS: In some patients who are hospitalized for acute illness,
      we have noted a reversible syndrome of headache, altered mental functioning,
      seizures, and loss of vision associated with findings indicating predominantly
      posterior leukoencephalopathy on imaging studies. To elucidate this syndrome, we
      searched the log books listing computed tomographic (CT) and magnetic resonance
      imaging (MRI) studies performed at the New England Medical Center in Boston and
      Hopital Sainte Anne in Paris; we found 15 such patients who were evaluated from
      1988 through 1994. RESULTS: Of the 15 patients, 7 were receiving
      immunosuppressive therapy after transplantation or as treatment for aplastic
      anemia, 1 was receiving interferon for melanoma, 3 had eclampsia, and 4 had acute
      hypertensive encephalopathy associated with renal disease (2 with lupus
      nephritis, 1 with acute glomerulonephritis, and 1 with acetaminophen-induced
      hepatorenal failure). Altogether, 12 patients had abrupt increases in blood
      pressure, and 8 had some impairment of renal function. The clinical findings
      included headaches, vomiting, confusion, seizures, cortical blindness and other
      visual abnormalities, and motor signs. CT and MRI studies showed extensive
      bilateral white-matter abnormalities suggestive of edema in the posterior regions
      of the cerebral hemispheres, but the changes often involved other cerebral areas,
      the brain stem, or the cerebellum. The patients were treated with
      antihypertensive medications, and immunosuppressive therapy was withdrawn or the
      dose was reduced. In all 15 patients, the neurologic deficits resolved within two
      weeks. CONCLUSIONS: Reversible, predominantly posterior leukoencephalopathy may
      develop in patients who have renal insufficiency or hypertension or who are
      immunosuppressed. The findings on neuroimaging are characteristic of subcortical
      edema without infarction.

PMID- 8559203
TI  - Ragweed immunotherapy in adult asthma.
AB  - BACKGROUND: Although allergen immunotherapy is effective for allergic rhinitis,
      its role in treating asthma is unclear. METHODS: We examined the efficacy of
      immunotherapy for asthma exacerbated by seasonal ragweed exposure. During an
      observation phase, adults with asthma who were sensitive to ragweed kept daily
      diaries and recorded peak expiratory flow rates between July and October. Those
      who reported seasonal asthma symptoms and medication use as well as decreased
      peak expiratory flow were randomly assigned to receive placebo or ragweed-extract
      immunotherapy in doses that increased weekly for an additional two years.
      RESULTS: During the observation phase, the mean (+/- SE) peak expiratory flow
      rate measured in the morning during the three weeks representing the height of
      the pollination season was 454 +/- 20 liters per minute in the immunotherapy
      group and 444 +/- 16 liters per minute in the placebo group. Of the 77 patients
      who began the treatment phase, 64 completed one year of the study treatment and
      53 completed two years. During the two treatment years, the mean peak expiratory
      flow rate was higher in the immunotherapy group (489 +/- 16 liters per minute,
      vs. 453 +/- 17 in the placebo group [P = 0.06] during the first year, and 480 +/-
      12 liters per minute, vs. 461 +/- 13 in the placebo group [P = 0.03] during the
      second). Medication use was higher in the immunotherapy group than in the placebo
      group during observation and lower during the first treatment year (P = 0.01) but
      did not differ in the two groups during the second year (P = 0.7). Asthma-symptom
      scores were similar in the two groups (P = 0.08 in year 1 and P = 0.3 in year 2).
      The immunotherapy group had reduced hay-fever symptoms, skin-test sensitivity to
      ragweed, and sensitivity to bronchial challenges and increased IgG antibodies to
      ragweed as compared with the placebo group; there was no longer a seasonal
      increase in IgE antibodies to ragweed allergen in the immunotherapy group after
      two years of treatment. Reduced medication costs were counterbalanced by the
      costs of immunotherapy. CONCLUSIONS: Although immunotherapy for adults with
      asthma exacerbated by seasonal ragweed exposure had positive effects on objective
      measures of asthma and allergy, the clinical effects were limited and many were
      not sustained for two years.

PMID- 8559204
TI  - Brief report: testicular and ovarian resistance to luteinizing hormone caused by
      inactivating mutations of the luteinizing hormone-receptor gene.

PMID- 8559205
TI  - Images in clinical medicine. Multiple myeloma.

PMID- 8559206
TI  - Acute spinal injury.

PMID- 8559207
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 6-1996. A 40-year-old man with a cough, increasing dyspnea, and
      bilateral nodular lung opacities.

PMID- 8559208
TI  - Acute myocardial infarction and left bundle-branch block--can we lift the veil?

PMID- 8559209
TI  - Management of myeloma with bisphosphonates.

PMID- 8559210
TI  - Is immunotherapy for asthma worthwhile?

PMID- 8559211
TI  - Social, institutional, and economic barriers to the exercise of patients' rights.

PMID- 8559212
TI  - Cocaine-associated myocardial ischemia.

PMID- 8559213
TI  - Cocaine-associated myocardial ischemia.

PMID- 8559214
TI  - Cocaine-associated myocardial ischemia.

PMID- 8559215
TI  - Cocaine-associated myocardial ischemia.

PMID- 8559216
TI  - Survival after age 80.

PMID- 8559217
TI  - Survival after age 80.

PMID- 8559218
TI  - Survival after age 80.

PMID- 8559219
TI  - Clinical problem-solving: hypereosinophilic syndrome.

PMID- 8559221
TI  - Clinical problem-solving: hypereosinophilic syndrome.

PMID- 8559220
TI  - Clinical problem-solving: hypereosinophilic syndrome.

PMID- 8559222
TI  - Clinical problem-solving: hypereosinophilic syndrome.

PMID- 8559223
TI  - Herpesvirus-like DNA sequence in angiosarcoma in a patient without HIV infection.

PMID- 8559224
TI  - Unemployed physicians.

PMID- 8559225
TI  - Patient advocacy in the 1990s.

PMID- 8559226
TI  - Whose right to genetic knowledge?
AB  - A new section in this issue of Nature highlights the growing demands of insurers
      for access to genetic information, the diversity of legislative responses, and
      the many scientific uncertainties. The history of genetics suggests a
      controversial way forward.

PMID- 8559227
TI  - Scientists challenged over 'unauthorized' export of data.

PMID- 8559228
TI  - Indian researchers press for stricter rules to regulate 'gene-hunting'.

PMID- 8559229
TI  - Russia approves gene therapy research grants.

PMID- 8559230
TI  - Cancer charity installs former critic as head.

PMID- 8559231
TI  - US court challenge may limit use of data in DNA banks.

PMID- 8559232
TI  - Embryo research barred from federal funds.

PMID- 8559233
TI  - Shot in the arm for medical policy body.

PMID- 8559234
TI  - Tokyo professor accused of perjury over evidence of HIV infection.

PMID- 8559235
TI  - Gene tests: who benefits from risk?
AB  - The insurance industry is likely to find it more difficult to use genetic data on
      disease susceptibility than some of its critics claim. But it is already
      contesting demands for strict controls on the way this data is used.

PMID- 8559236
TI  - Complexity limits the powers of prediction.

PMID- 8559237
TI  - DNA chips intensify the sequence search.

PMID- 8559238
TI  - Clinical trials.

PMID- 8559240
TI  - . . . meanwhile, elsewhere in Italy.

PMID- 8559239
TI  - Birth dates in Florence...

PMID- 8559241
TI  - Inexpressible trinucleotides.

PMID- 8559242
TI  - Medical genetics. Crystal-clear chloride channels.

PMID- 8559243
TI  - Conservation biology. Dangerous liaisons and disease.

PMID- 8559244
TI  - Gene expression. When the junk isn't junk.

PMID- 8559245
TI  - The ins and outs of fertilization.

PMID- 8559246
TI  - Protein folding in the central cavity of the GroEL-GroES chaperonin complex.
AB  - The chaperonin GroEL is able to mediate protein folding in its central cavity.
      GroEL-bound dihydrofolate reductase assumes its native conformation when the
      GroES cofactor caps one end of the GroEL cylinder, thereby discharging the
      unfolded polypeptide into an enclosed cage. Folded dihydrofolate reductase
      emerges upon ATP-dependent GroES release. Other proteins, such as rhodanese, may
      leave GroEL after having attained a conformation that is committed to fold.
      Incompletely folded polypeptide rebinds to GroEL, resulting in structural
      rearrangement for another folding trial in the chaperonin cavity.

PMID- 8559247
TI  - A canine distemper virus epidemic in Serengeti lions (Panthera leo).
AB  - Canine distemper virus (CDV) is thought to have caused several fatal epidemics in
      canids within the Serengeti-Mara ecosystem of East Africa, affecting silver
      backed jackals (Canis mesomelas) and bat-eared foxes (Otocyon megalotis) in 1978
      (ref. 1), and African wild dogs (Lycaon pictus) in 1991 (refs 2, 3). The large,
      closely monitored Serengeti lion population was not affected in these epidemics.
      However, an epidemic caused by a morbillivirus closely related to CDV emerged
      abruptly in the lion population of the Serengeti National Park, Tanzania, in
      early 1994, resulting in fatal neurological disease characterized by grand mal
      seizures and myoclonus; the lions that died had encephalitis and pneumonia. Here
      we report the identification of CDV from these lions, and the close phylogenetic
      relationship between CDV isolates from lions and domestic dogs. By August 1994,
      85% of the Serengeti lion population had anti-CDV antibodies, and the epidemic
      spread north to lions in the Maasai Mara National reserve, Kenya, and uncounted
      hyaenas, bat-eared foxes, and leopards were also affected.

PMID- 8559248
TI  - A common molecular basis for three inherited kidney stone diseases.
AB  - Kidney stones (nephrolithiasis), which affect 12% of males and 5% of females in
      the western world, are familial in 45% of patients and are most commonly
      associated with hypercalciuria. Three disorders of hypercalciuric nephrolithiasis
      (Dent's disease, X-linked recessive nephrolithiasis (XRN), and X-linked recessive
      hypophosphataemic rickets (XLRH)) have been mapped to Xp11.22 (refs 5-7). A
      microdeletion in one Dent's disease kindred allowed the identification of a
      candidate gene, CLCN5 (refs 8,9) which encodes a putative renal chloride channel.
      Here we report the investigation of 11 kindreds with these renal tubular
      disorders for CLCN5 abnormalities; this identified three nonsense, four missense
      and two donor splice site mutations, together with one intragenic deletion and
      one microdeletion encompassing the entire gene. Heterologous expression of wild
      type CLCN5 in Xenopus oocytes yielded outwardly rectifying chloride currents,
      which were either abolished or markedly reduced by the mutations. The common
      aetiology for Dent's disease, XRN and XLRH indicates that CLCN5 may be involved
      in other renal tubular disorders associated with kidney stones.

PMID- 8559249
TI  - Preferential activation of midbrain dopamine neurons by appetitive rather than
      aversive stimuli.
AB  - Midbrain dopamine systems are crucially involved in motivational processes
      underlying the learning and execution of goal-directed behaviour. Dopamine
      neurons in monkeys are uniformly activated by unpredicted appetitive stimuli such
      as food and liquid rewards and conditioned, reward-predicting stimuli. By
      contrast, fully predicted stimuli are ineffective, and the omission of predicted
      reward depresses their activity. These characteristics follow associative
      learning rules, suggesting that dopamine responses report an error in reward
      prediction. Accordingly, neural network models are efficiently trained using a
      dopamine-like reinforcement signal. However, it is unknown whether the responses
      to environmental stimuli concern specific motivational attributes or reflect more
      general stimulus salience. To resolve this, we have compared dopamine impulse
      responses to motivationally opposing appetitive and aversive stimuli. In contrast
      to appetitive events, primary and conditioned non-noxious aversive stimuli either
      failed to activate dopamine neurons or, in cases of close resemblance with
      appetitive stimuli, induced weaker responses than appetitive stimuli. Thus,
      dopamine neurons preferentially report environmental stimuli with appetitive
      rather than aversive motivational value.

PMID- 8559250
TI  - Calcium-dependent interaction of N-type calcium channels with the synaptic core
      complex.
AB  - Neurotransmitter release is initiated by influx of Ca2+ through voltage-gated
      Ca2+ channels, within 200 microseconds of the action potential arriving at the
      synaptic terminal, as the Ca2+ concentration increases from 100 nM to > 200
      microM. Exocytosis requires high Ca2+ concentration, with a threshold of 20-50
      microM and half-maximal activation at 190 microM. The synaptic membrane proteins
      syntaxin, 25K synaptosome-associated protein (SNAP25), and vesicle-associated
      membrane protein (VAMP)/synaptobrevin, are thought to form a synaptic core
      complex which mediates vesicle docking and membrane fusion. Synaptotagmin may be
      the low-affinity Ca(2+)-sensor, but other Ca(2+)-sensors are involved as residual
      neurotransmission persists in synaptotagmin-null mutants. Syntaxin binds to N
      type Ca2+ channels at a site in the intracellular loop connecting domains II and
      III. Here we describe Ca(2+)-dependent interaction of this site with syntaxin and
      SNAP25 which has a biphasic dependence on Ca2+, with maximal binding at 20 microM
      free Ca2+, near the threshold for transmitter release. Ca(2+)-dependent
      interaction of Ca2+ channels with the synaptic core complex may be important for
      Ca(2+)-dependent docking and fusion of synaptic vesicles.

PMID- 8559251
TI  - Two mechanisms of quantized calcium release in skeletal muscle.
AB  - Skeletal muscle uses voltage sensors in the transverse tubular membrane that are
      linked by protein-protein interactions to intracellular ryanodine receptors,
      which gate the release of calcium from the sarcoplasmic reticulum. Here we show,
      by using voltage-clamped single fibres and confocal imaging, that stochastic
      calcium-release events, visualized as Ca2+ sparks, occur in skeletal muscle and
      originate at the triad. Unitary triadic Ca(2+)-release events are initiated by
      the voltage sensor in a steeply voltage-dependent manner, or occur spontaneously
      by a mechanism independent of the voltage sensor. Large-amplitude events also
      occur during depolarization and consist of two or more unitary events. We propose
      a 'dual-control' model for discrete Ca2+ release events from the sacroplasmic
      reticulum that unifies diverse observations about Ca(2+)-signalling in frog
      skeletal muscle, and that may be applicable to other excitable cells.

PMID- 8559252
TI  - Cloning and characterization of the thyroid iodide transporter.
AB  - Iodide (I-) is an essential constituent of the thyroid hormones T3 and T4, and is
      accumulated by the thyroid. The transport of iodide, the first step in thyroid
      hormogenesis, is catalysed by the Na+/I- symporter, an intrinsic membrane protein
      that is crucial for the evaluation, diagnosis and treatment of thyroid disorders.
      Although several other important thyroid proteins involved in hormogenesis have
      been characterized, the Na+/I- symporter has not. Here we report the isolation of
      a complementary DNA clone that encodes this symporter, as a result of functional
      screening of a cDNA library from a rat thyroid-derived cell line (FRTL-5) in
      Xenopus laevis oocytes. Oocyte microinjection of an RNA transcript made in vitro
      from this cDNA clone elicited a more than 700-fold increase in perchlorate
      sensitive Na+/I- symport activity over background. To our knowledge, this is the
      first iodide-transporting molecule to have its cDNA cloned, providing a missing
      link in the thyroid hormone biosynthetic pathway.

PMID- 8559253
TI  - A mammalian RNA editing enzyme.
AB  - Editing of RNA by site-selective adenosine deamination alters codons in brain
      expressed pre-messenger RNAs for glutamate receptor (GluR) subunits including a
      codon for a channel determinant (Q/R site) in GluR-B, which controls the Ca2+
      permeability of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
      receptors. Editing of GluR pre-mRNAs requires a double-stranded RNA (dsRNA)
      structure formed by exonic and intronic sequences and is catalysed by an unknown
      dsRNA adenosine deaminase. Here we report the cloning of complementary DNA for
      RED1, a dsRNA adenosine deaminase expressed in brain and peripheral tissues that
      efficiently edits the Q/R site in GluR-B pre-mRNA in vitro. This site is poorly
      edited by DRADA, which is distantly sequence-related to RED1. Both deaminases
      edit the R/G site in GluR-B pre-mRNA, indicating that members of an emerging gene
      family catalyse adenosine deamination in nuclear transcripts with distinct but
      overlapping substrate specificities.

PMID- 8559254
TI  - A mammalian gene with introns instead of exons generating stable RNA products.
AB  - The nucleoli of eukaryotic cells are the sites of ribosomal RNA transcription and
      processing and of ribosomal subunit assembly. They contain multiple small
      nucleolar RNAs (snoRNAs), several of which are essential for rRNA maturation. The
      U3, U8 and U13 snoRNA genes are transcribed independently, whereas U14-U24, as
      well as E3, are located within introns of protein-coding genes, most of whose
      functions are linked to translation. These snoRNAs are co-transcribed with their
      host pre-mRNAs and released by processing from excised introns. Here we show
      that, in addition to U22, seven novel fibrillarin-associated snoRNAs, named U25
      U31, are encoded within different introns of the unusually compact mammalian U22
      host gene (UHG). All seven RNAs exhibit extensive (12-15 nucleotides)
      complementarity to different segments of the mature rRNAs, followed by a C/AUGA
      ('U-turn') sequence. The spliced UHG RNA, although it is associated with
      polysomes, has little potential for protein coding, is short-lived, and is poorly
      conserved between human and mouse. Thus, the introns rather than the exons
      specify the functional products of UHG.

PMID- 8559255
TI  - Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray
      mass spectrometry.
AB  - Molecular analysis of complex biological structures and processes increasingly
      requires sensitive methods for protein sequencing. Electrospray mass spectrometry
      has been applied to the high-sensitivity sequencing of short peptides, but
      technical difficulties have prevented similar success with gel-isolated proteins.
      Here we report a simple and robust technique for the sequencing of proteins
      isolated by polyacrylamide gel electrophoresis, using nano-electrospray tandem
      mass spectrometry. As little as 5 ng protein starting material on Coomassie- or
      silver-stained gels can be sequenced. Multiple-sequence stretches of up to 16
      amino acids are obtained, which identify the protein unambiguously if already
      present in databases or provide information to clone the corresponding gene. We
      have applied this method to the sequencing and cloning of a protein which
      inhibits the proliferation of capillary endothelial cells in vitro and thus may
      have potential antiangiogenic effects on solid tumours.

PMID- 8559256
TI  - Newer techniques for noninvasive vascular imaging.

PMID- 8559257
TI  - Ethical responsibilities in a managed care system.
AB  - Managed care is becoming increasingly important in health care. A number of
      ethical questions arise in this system. This paper examines the ethical
      responsibilities of four players in a managed care system: i) the insurance
      company; ii) the patient; iii) the primary care provider; and iv) the specialist.

PMID- 8559258
TI  - Dislocation of the knee. A case report.

PMID- 8559259
TI  - Neonatal herpes simplex virus (HSV) infections.
AB  - Prevention remains the best form of "treatment" of neonatal HSV infection. Prompt
      work-up and initiation of antiviral therapy provide the best outcome once
      infection has occurred. It is critical that practitioners be aware of the urgency
      of initiation of therapy as well as the signs/symptoms of maternal and neonatal
      HSV infection.

PMID- 8559260
TI  - [Cerebral vasospasm following subarachnoid hemorrhage as studied from the
      mechanism of physiological smooth muscle contraction].

PMID- 8559261
TI  - [Cerebrospinal fluid leak after cranial base surgery].
AB  - We investigated the incidence, prevention and management of postoperative
      cerebrospinal fluid (CSF) leaks in 64 cranial base surgeries (18 transzygomatic
      subtemporal approaches, 14 transpetrous approaches, 21 suboccipital approaches
      and 11 lateral approaches). The incidence was 13% (8/64); the lateral approach
      had the highest incidence (25%) among the four surgical approaches. The CSF
      leakage usually occurred as rhinorrhea, but the lateral approach resulted in the
      subcutaneous CSF retention and CSF leakage from the surgical wound. Six CSF leaks
      developed within 10 days after surgery ("early onset") and two developed 21 and
      23 days after surgery ("late onset"). Preventive lumbar CSF drainage was
      significantly effective. Post-operative CSF leak occurred in none of 8 cases
      using preventive lumbar CSF drainage and in 8 out of 56 cases without it (P <
      0.01). Lumbar CSF drainage was also effective in the treatment of the
      postoperative CSF leaks; it cured 5 out of 8 CSF leaks. All of the five CSF leaks
      which were cured by lumbar drainage were of the "early onset" type. Both of the
      two "late onset" CSF leaks needed surgical treatment.

PMID- 8559262
TI  - [Encapsulated dopamine-secreting cells transplanted into the brain: a possible
      therapy for Parkinson's disease].
AB  - Encapsulation of neurosecretory cells within a semipermeable membrane may
      possibly isolate the enclosed cells from the host immune system and allow inward
      diffusion of nutrients and outward diffusion of neurotransmitters. Moreover, the
      encapsulation procedure may prevent the tumor formation of enclosed cells, when
      they are derived from tumor cells. In the present study, PC12 cells, a
      dopaminergic cell line derived from a rat pheochromocytoma, were enclosed within
      an agarose/poly (styrene sulfonic acid) (agarose/PSSa) mixture and transplanted
      into the brains of rats (allogeneic transplantation) or guinea pigs (xenogeneic
      transplantation). Tyrosine hydroxylase (TH) immunoreactive PC12 cells within the
      microcapsules were observed in all rats and guinea pigs at least up to five weeks
      after transplantation. PC12 cells were round in shape and of relatively uniform
      small size. Although PC12 cells occasionally formed cell clusters, the formation
      of a tumor was not observed. The host reaction to agarose/PSSa microcapsules was
      minimum. The degree of glial fibrillary acidic protein (GFAP) positive astrocyte
      density around the microcapsules was similar to that around injection tracks.
      There was no apparent immunological rejection around the capsules. High
      performance liquid chromatography with electrochemical detection (HPLC-EC) showed
      basal and potassium-evoked release of dopamine from the PC12 cell-enclosed
      microcapsules in vitro. Although our data is preliminary, we believe that
      agarose/PSSa microcapsules are promising for producing semipermeable membranes
      that enable allo-and xenotransplantation of neurosecretory cells into the brain
      in the absence of systemic immunosuppression. This approach is expected to be
      applied in Parkinson's disease in the near future.

PMID- 8559263
TI  - [Problems encountered with a programmable pressure valve (SOPHY) positioned in
      the chest wall].
AB  - Sixty-eight hydrocephalic patients were treated with a shunt system that
      incorporated a SOPHY programmable valve. This device is very effective for
      treating disorders of CSF circulation. However, when the valve is placed on the
      scalp, it produces artifacts on MR imaging due to its small magnetic rotor, and
      may cause necrosis of the scalp above it. On the other hand, when it is
      positioned on the chest, MR artifacts decrease and exchanging the valve devices
      becomes easier. Therefore, we have positioned the device on the chest. However,
      some complications were encountered, such as the turning over of the valve in the
      subcutaneous pocket and the twisting of the shunt tube. Moreover, the shunt tube
      may stretch due to growth of the neck during development in infantile patients or
      extension of the neck during exercise. These complications are associated only
      with subcutaneous placement on the chest, so we conclude that such a valve, if
      placed on the chest, should be placed in a lower position on the chest, and if MR
      examination will not be performed in the foreseeable future, we recommend that it
      be placed on the occipital scalp, especially in infantile patients.

PMID- 8559264
TI  - [Promotive factors of chronic subdural hematoma in relation to age].
AB  - To reveal the pathogenesis of chronic subdural hematoma (CSDH), 256 patients with
      CSDH over 1 year of age were studied in relation to various traumatic or
      nontraumatic promotive factors of CSDH including arachnoid cyst, implantation of
      a cerebrospinal fluid shunt, secondary cerebral atrophy, coagulopathies and past
      history of acute subdural hematoma or effusion. All patients were grouped
      according to decade of age. The incidences of associated promotive factors were
      individually analyzed in each group. The incidences of associated promotive
      factors in the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th decades of life were
      71%, 89%, 56%, 33%, 9%, 11%, 8%, 8% and 5%, respectively. Thus, they were divided
      into two groups; youth (1st to 4th decade: n = 34) and elder (5th to 9th decade:
      n = 222). The incidences of associated promotive factors were 62% and 8%,
      respectively (P < 0.001). Severity of head injury received was also evaluated in
      these two groups. In the youth group, 15 out of 34 patients (44.1%) had received
      severe head injuries with loss of consciousness, while in the elder group, only
      22 out of 222 patients (9.9%) had received severe head injuries (P < 0.001). The
      analysis was repeated after each group was divided into two subgroups regarding
      the coexistence of promotive factors. Among the youth group, 13 patients had no
      promotive factors and 21 had one or more promotive factors. In those without any
      promotive factor, 9 out of 13 had received severe head injuries with loss of
      consciousness, while in those with promotive factors, 6 out of 21 had received
      severe head injuries. On the other hand, majority of the elder group had not
      received severe head injuries irrespective of whether patients had promotive
      factors or not. The present study revealed that majority of young CSDH patient
      had some promotive factors or severe head injuries with loss of consciousness,
      and that majority of patients aged over 40 years had no promotive factors and did
      not receive severe head injuries.

PMID- 8559265
TI  - [A case of amnesic syndrome caused by hematoma in the left anterior medial
      thalamus].
AB  - We reported a case of amnestic syndrome caused by a hematoma in the left
      thalamus. The case was that of a 68-year-old, right-handed man who suddenly
      showed amnestic syndrome. He had neither motor paresis nor sensory disturbance.
      Clinical examination showed he had disorientation, anterograde amnesia and mild
      retrograde amnesia. Immediate recall and remote memory were intact, but recent
      memory was severely impaired. CT scan revealed a high density area in the
      anterior medial part of the left thalamus. We concluded that amnesia in this
      patient was caused by fasciculus mamillothalamicus damage because of a hematoma
      during thalamic hemorrhage.

PMID- 8559266
TI  - [A case of moyamoya disease in the aged associated with cerebral embolism].
AB  - We reported a rare case of Moyamoya disease in the aged associated with cerebral
      embolism. A 76-year-old female was brought into our hospital by ambulance 30 min
      after an attack of fainting. She had no past history of cerebrovascular disease.
      On admission her consciousness level was JCS 3-IA and she showed Rt. hemiparesis
      ECG exhibited Af tachycardia. No abnormal region was recognized on brain CT.
      Emergency cerebral angiograms (AG) disclosed that unexpectedly she had Moyamoya
      disease. Stenotic or occluded lesions were seen from bilateral IC terminal
      portions to MCA and ACA, and basal moyamoya vessels were visualized. Transdural
      anastomosis was poor and posterior circulation was the main source of collateral
      flow. Mode of onset and neurological signs suggested that the cause of the attack
      was Lt. MCA occlusion at its sphenoidal portion by cardiogenic embolism.
      Superselective endovascular fibrinolysis was carried out by the use of urokinase
      and low molecular weight Dextran and Lt. MCA was able to be recanalized. She was
      recovered without neurological deficit. Lt. STA-MCA anastomosis and encephalo
      myosynangiosis was performed in the chronic stage because stenosis had remained
      in Lt. MCA and hypo-perfusion in bilateral frontal lobes was presented on SPECT.
      Post-operative AG demonstrated that Lt. MCA was occluded but Lt. frontal lobe was
      supplied with plenty of blood flow from Lt. STA. During the next day morning, she
      had another attack of fainting and showed moderate consciousness disturbance and
      motor aphasia. No abnormal change was noticed on brain CT. Emergency AG revealed
      that Lt. STA had become stuffed up with embolic and bypass flow had disappeared.
      Superselective endovascular fibrinolysis was able to recanalize the blood flow
      imperfectly, but mild motor apasia remained due to Lt. frontal infarction.

PMID- 8559267
TI  - [Anterior choroidal artery territory infarction with transcortical sensory
      aphasia after a neck clipping of left internal carotid artery aneurysms: a case
      report].
AB  - Anterior choroidal artery (Ach A) syndrome is widely known to be composed of a
      triad of hemiparesis, hemisensory loss and homonymous hemianopia. The authors
      report a case of Ach A-territory infarction after a direct operation for internal
      carotid artery aneurysms, which presented transcortical sensory aphasia in
      association with the characteristic triad. The literature and several previously
      reported cases with dominant and nondominant cerebral hemisphere signs in AcH A
      infarction are reviewed. The danger of Ach A occlusion and the importance of
      preserving it during aneurysm surgery are emphasized.

PMID- 8559268
TI  - A case of calcification of the cervical ligamentum flavum.
AB  - We report a case of cervical myelopathy caused by the calcification of the
      cervical ligamentum flavum. A 42-year-old woman with gait disturbance and an
      episode of dysuria was transferred to our hospital on June 30, 1994. Neurological
      examination revealed only a mild right hemiparesis. A plain neck X-ray and a
      tomogram revealed a nodular calcification in the posterior part of the spinal
      canal at the level of C5/6. Three dimensional computed tomography clearly
      demonstrated that the mass consisted of three nodular structures on the vertebral
      lamina. Magnetic resonance images demonstrated severe compression of the spinal
      cord by the mass whose intensity was low. The mass was removed en bloc together
      with the ligamentum flavum and C5 and C6 lamina. The mass showed no continuity to
      the dura mater. The calcification was confined within the ligament. The patient's
      neurological deficits were resolved two weeks after the surgery. X-ray
      diffraction study demonstrated the component of the mass was found to be pure
      hydroxyapatite. Clinical features of calcification of the ligamentum flavum are
      reviewed from 85 reported cases including ours, and the difference between this
      calcification and the ossification of the ligament is emphasized. Calcification
      of the ligamentum flaum is a distinct clinical entity.

PMID- 8559269
TI  - [Clinical application of functional mapping; the present state of the art and its
      future prospects: (series 1) functional MRI: signal mechanism of fMRI and
      quantification of brain function by echo planar imaging].

PMID- 8559270
TI  - Craniospinal arachnoid cyst: case report.
AB  - We encountered a rare case of craniospinal arachnoid cyst. A 54-year-old woman
      was admitted to our clinic for headache, posterior nuchal pain, and vomiting,
      which had started one month before. On admission she was drowsy, and neurological
      examination revealed papilledema and prompt deep tendon reflexes bilaterally. T1
      weighted images of MRI revealed a homogeneous, round, low density mass in the
      left cerebellar hemisphere which extended down on the dorsal side of the spinal
      cord to the level of C2. It was high intensity on T2 weighted images and was not
      enhanced by Gd-DTPA. The fourth ventricle was compressed and obstructed and
      hydrocephalus was observed. An operation was performed via a left suboccipital
      craniectomy with C1 laminectomy. A large cyst was located in the left cerebellar
      hemisphere, and it extended into the spinal canal down to the C2 level where the
      cyst compressed the spinal cord right-anteriorly. The content of the cyst was
      xanthochromic fluid. After the removal of as much of the cyst as possible, the
      flattened tonsil was seen just dorsal to the medulla. The cyst extended into the
      cerebellar hemisphere via the widened fissura secunda. The arachnoid of the
      cisterna magna was incised and communication between the cisterna magna and the
      cyst was made. The cyst was markedly reduced on the following day, and
      disappeared on the 50th postoperative day. The patient was discharged without
      neurological deficit. Pathological diagnosis of the cyst wall in the cerebellum
      was that the molecular layer of the cerebellar cortex was covered by arachnoid
      membrane, which indicated arachnoid cyst. Five such cases have been reported
      apart from this one. The therapy is the extirpation of the cyst wall and making
      communication between the arachnoid cyst and the subarachnoid space. The etiology
      of craniospinal arachnoid cyst is not well known but postoperative prognosis is
      good.

PMID- 8559271
TI  - [A case of dural AVM detected after STA-MCA anastomosis].
AB  - A case of dural arteriovenous malformation (AVM) in the posterior cranial fossa
      detected after STA-MCA anastomosis surgery. A 52-year-old male consulted a
      neighbourhood hospital for sudden headache and vomiting. He was diagnosed as
      having intraventricular hemorrhage on CT scan. Though the obstruction of the
      right internal carotid artery was revealed angiographically, his symptoms
      improved after conservative therapy. Two weeks after onset, his consciousness
      deteriorated and he developed left hemiparesis. Thereafter, he was transferred to
      our hospital. After thorough examination, right STA-MCA anastomosis surgery was
      performed. Approximately 2 months after surgery, right tinnitus developed and
      gradually exacerbated. Since it was thought to be due to increased blood flow in
      the right superficial temporal artery, it was kept under observation. On
      angiogram, 8 months after surgery, good blood flow supplied from the right
      superficial temporal artery to the territory of the right middle cerebral artery
      was shown, and a dural AVM fed by the right occipital artery was found. Fourteen
      months after the surgery, an enlarged dural AVM with backflow to the superficial
      cerebral veins fed by the enlarged right occipital artery and right ascending
      pharyngeal artery was revealed. Embolization therapy to the right occipital and
      ascending pharyngeal artery was performed using coils and ivalon, and irradiation
      of 30 Gy was added. After this treatment, right tinnitus improved. On angiography
      2 years later, transverse sinus was slightly visible via the right occipital
      artery and ascending pharyngeal artery, but the dural AVM was significantly
      reduced. The origin of dural AVMs remains controversial. In our case, dural AVM
      was not found before the STA-MCA anastomosis surgery, and sinus thrombosis was
      not found throughout the course of observation. It is thought that the occult
      dural AVM was disclosed and enlarged by the increased blood flow through the
      external carotid artery via the STA-MCA anastomosis. Therefore, the dural AVM
      seemed to be congenital in origin.

PMID- 8559272
TI  - [A case of anterior cerebral artery dissecting aneurysm].
AB  - The incidence of intracranial dissecting aneurysms is lower than that of berry
      aneurysms. Following the recent spread of the use of cerebral angiography,
      however, the number of patients identified as having this type of aneurysm has
      been increasing. In a majority of cases of intracranial dissecting aneurysms, the
      aneurysm afflicted the vertebral and basilar arteries. After these, the internal
      carotid artery and the middle cerebral artery are the next most frequently
      affected. It is very rare that this type of aneurysm develops in the anterior
      cerebral artery. According to our search of the literature, only 17 cases of
      dissecting aneurysm of the anterior cerebral artery have been reported to date
      (including the case to be presented here). The case we recently encountered was
      that of a 52-year-old male. On October 25, 1994, the man suddenly developed a
      headache and strong paresis of the left leg while performing clerical work. The
      plain head CT, taken next day, revealed low density in the area supplied by the
      right anterior cerebral artery. An angiogram taken 6 days after onset disclosed
      characteristic signs of dissecting aneurysm (i.e., double lumen, etc.) at the A2
      segment of the right anterior cerebral artery, as well as the presence of non
      ruptured berry aneurysms at the bifurcation of the right middle cerebral artery.
      The non-ruptured berry aneurysms were treated by neck clipping, while the
      dissecting aneurysms were treated conservatively. The patient was discharged on
      March 21, 1995, without needing any assistance to walk. We analyzed the 17
      reported cases of dissecting aneurysms of the anterior cerebral artery. The cause
      of this aneurysm was often hypertension, and only 3 of the 17 cases were rated as
      being idiopathic cases. The site of this aneurysm was often the pericallosal
      artery (segments A2, A3, etc.). Of the 17 patients, 11 were middle-aged or
      elderly (over 40). The male-to-female ratio was 13: 4, indicating a predominance
      of males. The incidence did not differ significantly between the right and left
      hemispheres. The number of ischemic cases was more than double that of
      hemorrhagic cases. Most ischemic cases had a good prognosis, even when treated
      conservatively. All 3 patients with the hemorrhagic type, who were treated
      conservatively, died.

PMID- 8559273
TI  - [Benign intracranial hypertension and continuous CSF pressure monitoring: case
      report].
AB  - The authors report a case of benign intracranial hypertension (BIH) treated with
      a ventriculoperitoneal shunt. A 62-year-old man was referred to the Kobe City
      General Hospital with several episodes of transient visual obscuration.
      Neurological examination on admission revealed bilateral papilledema and a right
      lower quadrantic homonymous hemianopsia. Computed tomography (CT) showed
      normalized ventricles and a low-density area in the left occipital lobe without
      mass effects. From the findings of magnetic resonance images (MRIs) the occipital
      lesion was diagnosed as a chronic intracerebral hematoma. Because the hematoma
      did not show mass effects. BIH was suspected to be responsible for the
      papilledema. In spite of intravenous administration of dexamethasone and glycerol
      for a week, a lumbar puncture showed an opening pressure of 360mm H2O. Several
      subsequent lumbar punctures failed to improve intracranial hypertension. The mean
      opening pressure of the last 6 punctures was 392mm H2O. The mean terminal
      pressure dropped to 32mm H2O after removal of 10m/ of cerebrospinal fluid (CSF).
      A spinal subarachnoid drainage was inserted at the level of L4-L5 interspace for
      continuous CSF pressure monitoring. The mean CSF pressure ranged from 20 to
      40mmHg. The continuous recording showed typical B waves frequently and plateau
      waves (A waves) occasionally. Removal of only 8m/ of CSF caused significant
      pressure reduction immediately. Then, pressure returned to the predrainage level
      about 35 minutes later. These findings supported the diagnosis of BIH. A
      ventriculoperitoneal shunt was inserted, which resulted in rapid and complete
      resolution of the papilledema. Postoperative CSF monitoring returned to normal
      pressure and waves. This case emphasizes the usefulness of continuous CSF
      pressure recording for the diagnosis and subsequent therapy of BIH.

PMID- 8559274
TI  - Does melatonin act on dopaminergic pathways in the mediobasal hypothalamus to
      mediate effects of photoperiod on prolactin secretion in the ram?
AB  - Previous studies have shown that the chronic administration of melatonin in the
      mediobasal hypothalamus (MBH) using micro-implants in Soay rams housed under long
      days causes a sustained decrease in the secretion of prolactin as occurs in
      response to short days. The purpose of this study was to investigate whether
      hypothalamic dopaminergic (DA) systems acting through D2 receptors may be
      involved in this melatonin-induced effect. Groups of Soay rams living under long
      days were treated in the MBH with micro-implants containing bromocriptine (BROM,
      DA D2 receptor agonist), or sulpiride (SULP, DA D2 receptor antagonist), given
      alone or in combination with melatonin (MEL), to establish whether the DA drugs
      would mimic or negate the effects of melatonin. A control group (C) received
      empty micro-implants or no treatment. The micro-implants were bilateral and were
      left in place for 14 weeks; the trial continued for a total of 28 weeks (14-week
      implant period and 14-week post-implant period) while the animals remained under
      long days. The ability of the micro-implants to release BROM and SULP for 14
      weeks was confirmed by incubating implants in vitro and testing for the presence
      of the compounds using a pituitary cell bioassay. MEL in the MBH induced a marked
      decrease in the blood plasma concentrations of prolactin during the implant
      period and an increase during the postimplant period (MEL vs. C, p < 0.001). BROM
      given alone induced a sustained decrease in the plasma concentrations of
      prolactin (less marked than MEL), while SULP caused an increase (BROM and SULP
      vs. C, p < 0.001); the effects were restricted to the implant period. BROM given
      in combination with MEL produced the same effect as MEL alone during both the
      implant and postimplant periods, while SULP given with MEL produced the same
      effect as MEL during the implant period, but impaired the increase in plasma
      concentrations of prolactin during the postimplant period (MEL + SULP vs. MEL, p
      < 0.001). There were changes in growth and moulting of the pelage correlated with
      the marked changes in the secretion of prolactin induced by MEL, but not related
      to the lesser effects of BROM and SULP. In conclusion, the long-term effects of
      the D2 agonist and antagonist are consistent with the inhibitory role of
      hypothalamic DA pathways in the homeostatic regulation of prolactin secretion.
      The inhibitory effect of the D2 agonist did not mimic that of MEL in the MBH,
      thus it is unlikely that the short day MEL signal operates primarily through a
      hypothalamic DA system to inhibit the secretion of prolactin. However, since the
      administration of the D2 antagonist in the MBH did influence the response to MEL,
      it is probable that DA pathways are involved in relaying the effects of MEL on
      the long-term cycle in the secretion of prolactin in the ram.

PMID- 8559275
TI  - Semicircadian rhythm of dopamine release in the mediobasal hypothalamus in awake
      rats during pseudopregnancy: evidence that a thyrotropin-releasing hormone
      analogue stimulates dopamine release and thereby inhibits prolactin secretion.
AB  - The release of dopamine (DA) from tuberoinfundibular (TIDA) neurons during
      prolactin (PRL) surge and nonsurge periods and the effects of the thyrotropin
      releasing hormone (TRH) analogue CG 3703 on DA and PRL secretion were studied in
      awake pseudopregnant (PSP) rats by simultaneous measurement of extracellular DA
      levels in the mediobasal hypothalamus (MBH) by means of microdialysis and of
      plasma PRL concentrations by radioimmunoassay of PRL in blood sampled from a
      permanent heart cannula. Since basal DA levels were low, the experiments were
      performed under local infusion of the reuptake inhibitor nomifensine (5 mumol/l),
      which increased extracellular DA levels 5-fold around the probe, but did not
      affect the occurrence of the nocturnal PRL surge on day 7-8 of PSP. Under
      nomifensine conditions, during the interphase (18.00-1.00 h) plasma PRL levels
      were low (< 50 ng/ml), while the DA release from TIDA neurons was elevated
      (approximately 250%) relative to the DA values measured during the phase when the
      nocturnal PRL surge occurred (100%; 1.00-12.00 h; plasma PRL levels were elevated
      to approximately 300 ng/ml). Thus, semicircadian rhythms were detected both for
      DA and PRL, which were broadly reciprocal in timing. The TRH analogue CG 3703
      (100 and 500 micrograms/animal i.v.), when administered at 00.00 h, dose
      dependently increased extracellular DA levels (to 300 and 500% of pretreatment
      values, respectively) and postponed the PRL surge in a corresponding manner (for
      approximately 2 and 3 h, respectively). Thus, in addition to its PRL-releasing
      effects, TRH can also suppress the PRL secretion by stimulating the release of DA
      from TIDA neurons, thereby increasing the inhibitor DAergic tone on lactotrophs.
      During the interphase, when DA levels were relatively elevated, administration of
      the DA blocking agent HA 966 (100 mg/kg body weight i.p.) at 20.00 h resulted in
      a short-lasting decrease in extracellular DA levels (to approximately 60% of
      pretreatment values for 30 min) accompanied by an immediate, short-lasting
      increase in PRL levels (to 400 ng/ml for approximately 1 h). Administration of CG
      3703 (500 micrograms/animal i.v.) in combination with HA 966 (100 mg/kg body
      weight i.p.) at 20.00 h prevented the decrease in DA levels and the rise in
      plasma PRL values. Thus, the TRH analogue and HA 966 counteracted each other
      regarding the DAergic system, which again illustrates the stimulatory effect of
      the TRH analogue on the release of DA from TIDA neurons. Moreover, our results
      suggest that the interphase and the phase during which the nocturnal PRL surge
      occurs under the condition of PSP differ with regard to the DAergic inhibition of
      the PRL secretion; during the interphase the DAergic inhibitory tone prevents the
      rise in PRL secretion, while during the nocturnal PRL surge period another factor
      in addition to a decrease in DA levels appears necessary to increase plasma PRL
      levels.

PMID- 8559276
TI  - Pattern of prolactin diurnal secretion in normal humans: evidence for nonlinear
      dynamics.
AB  - Prolactin (PRL) circadian profiles were analyzed using methods of nonlinear
      dynamics, directly from the experimental data, by combining in a single time
      series (432 measurements), six individual 24-hour PRL profiles (72 measurements
      per profile, sampling interval = 20 min), obtained from young healthy human
      volunteers (4 males, 2 females), under basal conditions. Significant
      autocorrelation exists between any given point of the time series and a limited
      number of its successors. Fourier analysis showed a dominant frequency of 1
      cycle/24 h, without sub-24-hour harmonics. Poincare section indicated the
      presence of a fractal attractor and a sketch of the attractor revealed a highly
      convoluted geometric structure with a conical contour. The box-counting dimension
      (D0), information dimension (D1) and correlation dimension (D2) of the attractor
      had low, fractal values, did not differ significantly from each other, and
      exhibited saturation at an embedding dimension of 2. The evidence taken together
      suggests that, under basal conditions, the daily changes in the peripheral blood
      levels of PRL are governed by nonlinear deterministic dynamics, with a dominant
      rhythm of 1 cycle/day mixed with a higher-frequency, low-amplitude signal.

PMID- 8559277
TI  - DNA binding of hypothalamic nuclear proteins on estrogen response element and
      preproenkephalin promoter: modification by estrogen.
AB  - Preproenkephalin (PPE) gene expression is specifically induced by estrogen in
      hypothalamus of ovariectomized (OVX) females, better than in male rats. To study
      estrogen actions on gene regulation, we have presently characterized protein-DNA
      interactions by use of a consensus estrogen response element (ERE) and a putative
      ERE from PPE gene, with nuclear extracts from hypothalamus. By use of the
      electrophoretic mobility shift assay (EMSA), ERE binding activity was detected in
      nuclear extracts from neuronal tissues including hypothalamus, hippocampus,
      striatum, cerebellum and frontal cortex, and non-neuronal tissues such as
      pituitary and uterus, but not lung of OVX female rats with a consensus ERE, as
      well as a 129-bp PCR fragment from PPE promoter and a hairpin oligonucleotide
      that contains a putative ERE of the rat PPE gene. The ERE binding was eliminated
      by the addition of specific ERE-containing oligonucleotide, but not control
      oligonucleotides. Protein and DNA associated and dissociated very rapidly. By use
      of supershift assay, interactions of estrogen receptor with ERE were demonstrated
      in hypothalamic nuclear extracts. The initial levels of specific ERE binding in
      the hypothalamic nuclear extracts were comparable between castrated male and OVX
      female rats. However, estrogen treatment, either estradiol or estradiol benzoate,
      produced a rapid and tissue-specific induction of a slow mobility complex of ERE
      binding in hypothalamic nuclear extracts from females, better than in male rats,
      presumably from other associated factors, or a conformational change or other
      posttranslational modifications. This estrogen-induced slow mobility complex of
      ERE binding in hypothalamus was not observed after treatment with progesterone or
      tamoxifen. These results suggest that specific ERE binding is present in rat
      hypothalamic nuclear proteins, which may contribute to the upregulation of PPE
      gene expression by estrogen, and that the sexually differentiated action of
      estrogen may be related to an estrogen-induced conformational change, but not to
      the initial level of ERE-binding activity.

PMID- 8559278
TI  - Central stimulation of oxytocin release in the lactating rat by N-methyl-D
      aspartate: requirement for coactivation through non-NMDA glutamate receptors or
      the glycine coagonist site.
AB  - Excitatory amino acid (EAA) neurotransmitters participate in the regulation of
      secretion of several neuropeptides, including oxytocin (OT), via actions at
      different receptors. In earlier studies, release of OT could be achieved reliably
      by injection into the supraoptic nucleus (SON) of alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA)/kainate receptor agonists, but not by
      treatment with N-methyl-D-aspartate (NMDA) alone. This prompted further
      examination of the possible role of NMDA receptors in OT release following
      central coapplication of NMDA and AMPA-site agonists, or of NMDA and agonists
      active at the glycine coagonist site. The agonists were injected into the right
      SON, the right paraventricular nucleus (PVN), or into the third ventricle (3V) of
      nonsuckled lactating rats. Cotreatment with NMDA and AMPA (using doses that alone
      did not include OT release) elicited a strong OT release in all animals by either
      the SON or the PVN route, and this was attenuated by pretreatment/cotreatment
      with specific antagonists of either the NMDA or the AMPA receptor. The SON area
      or 3V coinjection of NMDA and the NMDA/glycine site agonists glycine or D-serine
      also induced OT discharges in all animals, while cotreatment in the PVN did not
      result in uniform OT discharges. This release was potently reduced by cotreatment
      with the specific NMDA/glycine site antagonist 5, 7-dichlorokynurenate (DCK). L
      Serine somewhat increased the frequency of discharge-type response to NMDA, while
      intra-SON coinjection of L-leucine did not stimulate OT release. D-Serine alone
      stimulated the release of OT much less than in combination with NMDA, and with no
      obvious dose dependence. The suckling-induced release of OT was attenuated, but
      not abolished, by DCK, while PRL release was briefly stimulated by this agent. A
      physiological role for the NMDA receptor in OT release is clearly supported by
      these studies. NMDA receptor activation in the lactating rat may result from
      either an allosteric stimulation by glycine site agonists, or a synergistic
      interaction with the AMPA/kainate group of excitatory amino acid receptors.

PMID- 8559279
TI  - Preoptic rather than mediobasal hypothalamic amino acid neurotransmitter release
      regulates GnRH secretion during the estrogen-induced LH surge in the
      ovariectomized rat.
AB  - Inhibitory and excitatory amino acid neurotransmitters have been suggested to
      participate in the feedback actions of estradiol (E2) on LH secretion. In the rat
      estrogen-receptive neurons have been demonstrated in the preoptic/anterior
      hypothalamic area (POA) and mediobasal hypothalamus/median eminence (MBH) and
      many of these neurons utilize gamma-aminobutyric acid (GABA) as neurotransmitter.
      The actions of excitatory amino acids (EAA) differ in ovariectomized (ovx) and
      ovx E2-substituted rats indicating that EAAs also participate in the positive
      feedback action of E2 on LH release. However, little information is available as
      to whether in vivo these transmitters exert their effects in the POA, where most
      of the GnRH perikarya are located, or in the MBH, i.e. at the nerve terminals.
      Therefore we conducted push pull cannula perfusions to compare the release rates
      of GABA, aspartate (ASP) and glutamate (GLU) in the MBH and POA. A subcutaneous
      implant of a silastic tube containing E2 resulted in LH surges in the afternoon
      of all treated animals. Prior to and during this LH surge the MBH release rates
      of neither GABA nor ASP nor GLU were significantly altered. In contrast, a
      conspicuous drop in preoptic GABA release occurred prior to and during the time
      of estrogen-induced LH surges and this was accompanied by enhanced preoptic
      secretion of ASP and GLU. In conclusion, we present the first data about amino
      acid release in the MBH during the E2-induced LH surge. Since only in the POA the
      LH surge is associated with changes in amino acid release, it appears that both
      inhibitory and excitatory amino acids act at the level of the GnRH cell bodies
      and/or dendrites and not on GnRH nerve terminals to mediate the feedback
      mechanism of E2 on LH release.

PMID- 8559280
TI  - Androgen and estrogen receptors coexist within individual neurons in the brain of
      the Syrian hamster.
AB  - Many aspects of reproductive neuroendocrine function and sexual behavior are
      responsive to both androgens and estrogens, suggesting that receptors for these
      steroid hormones may reside within single cells in brain regions that control
      reproductive function. We determined the distribution of estrogen receptor
      containing neurons in 40-microns coronal brain sections in gonadectomized, DHT
      treated male Syrian hamsters using immunocytochemistry with the H222 antibody (10
      micrograms/ml; Abbott Laboratories). Subsequently, we colocalized estrogen
      receptors with androgen receptors using the PG-21 antibody (0.5 microgram/ml;
      G.S. Prins). In males, the distribution of estrogen receptor-containing neurons
      was similar to that reported previously for the female hamster. Colocalization of
      androgen and estrogen receptor immunoreactivity was observed in brain regions
      that contain numerous androgen and estrogen receptor-positive neurons, including
      subdivisions of the medial preoptic area, bed nucleus of the stria terminals,
      ventromedial nucleus of the hypothalamus, and the amygdalohippocampal area.
      Single-labelled estrogen receptor-containing neurons were most numerous in the
      amygdalohippocampal area and the rostral medial preoptic nucleus; androgen
      receptor-immunoreactive cells were most abundant in the ventral premammillary
      nucleus and the lateral septum. These data suggest the potential of androgens and
      estrogens to influence neuronal function within individual steroid receptor
      containing neurons of the hamster limbic system.

PMID- 8559281
TI  - Identification, cellular localization and in vitro release of a novel teleost
      melanin-concentrating hormone gene-related peptide.
AB  - The melanin-concentrating hormone (MCH) precursor encodes MCH and a second
      peptide named neuropeptide EI (NEI) in mammals, neuropeptide EV (NEV) in
      salmonids and MCH gene-related peptide (Mgrp) in other fish. The primary
      structure of the putative Mgrp of the cichlid fish tilapia (Oreochromis
      mossambicus) appears to be very different from mammalian NEI and salmonid NEV. To
      investigate the processing and release of tilapia Mgrp (tMgrp), in the present
      study an antiserum was raised against synthetic tMgrp. By immunocytochemistry,
      tMgrp immunoreactivity was colocated with MCH immunoreactivity in the tilapia
      hypothalamus and pituitary. In addition, a tMgrp enzyme-linked immunosorbent
      assay in combination with reversed phase HPLC was used to demonstrate the
      presence of processed tMgrp in tilapia hypothalamus and pituitary. The release of
      tMgrp from neuro-intermediate lobes (NILs) of tilapia pituitaries was
      demonstrated after in vivo incubation of chopped NILs. Depolarizing
      concentrations of potassium significantly stimulated tMgrp release. Six weeks of
      adaptation of tilapia to white or black backgrounds had no effect on in vitro
      tMgrp release or on the tMgrp content of NIL and hypothalamus. Tilapia Mgrp,
      unlike MCH, had no effect on tilapia scale melanophores, nor did it modulate the
      melanin-concentrating effect of MCH. We conclude that tMgrp is processed from the
      MCH preprohormone, that it is released in vitro, and that the peptide has no
      direct role in the melanin concentration of fish scale melanophores. Therefore a
      neuroendocrine or neuromodulatory function is proposed for tMgrp.

PMID- 8559282
TI  - Stress-induced inhibition of the hypothalamic-pituitary-thyroid axis is
      attenuated in the aged Fischer 344/N male rat.
AB  - Aging is associated with a progressive decrement in the basal activity of the
      hypothalamic-pituitary-thyroid axis in male Fischer 344/N rats. The aim of this
      study was to determine whether stress influences the activity of this axis in
      young and old rats. As prolactin and growth hormone share some regulatory
      mechanisms with thyrotropin-releasing and thyroid-stimulating hormones, which are
      influenced by stress, the plasma levels of these two hormones were also
      determined during immobilization (Immo). To accomplish this, young (3-month-old)
      and old (23-month-old) male 344/N Fischer rats were immobilized for 2 h; blood
      was collected by cannulation from the tail artery at different intervals during
      Immo (0, 5, 30, 60, and 120 min), and brains were removed at the end of Immo. The
      basal plasma levels of thyroid-stimulating hormone were similar in both groups,
      but were significantly and progressively inhibited by Immo in young, but not in
      old rats. The baseline plasma levels of total triiodothyronine were slightly
      lower in old than in young rats; Immo caused a significant decrease of total
      triiodothyronine levels only in the young animals. The baseline plasma levels of
      free triiodothyronine were similar and were not altered by Immo in either age
      group. The paraventricular nucleus thyrotropin-releasing hormone mRNA levels were
      lower in old than in young rats under basal conditions; under stress they were
      significantly inhibited in young, but remained unchanged in old rats. The basal
      thyroid-stimulating hormone beta mRNA levels in the anterior pituitary were
      significantly lower in old than in young rats, but were not affected by Immo in
      either age group. The plasma prolactin levels were similar at baseline and were
      significantly increased by Immo in both age groups, but significantly more in old
      than in young rats. The plasma growth hormone levels were also similar at
      baseline; they were significantly decreased by Immo to a similar extent in both
      age groups. In summary, these data indicate that the stress-induced decrease in
      plasma thyroid-stimulating hormone is in part mediated at the level of the
      hypothalamic thyrotrophin-releasing hormone neuron and that this phenomenon is
      attenuated in the aged rat.

PMID- 8559283
TI  - Modulation of regulatory and catalytic subunit levels of cAMP-dependent protein
      kinase A in anterior pituitary cells in response to direct activation of protein
      kinases A and C or after GnRH stimulation.
AB  - We have previously shown that direct activation of protein kinase A (PKA) and
      protein kinase C (PKC) induced changes in the expression of genes coding for PKA
      RII beta and C alpha subunit isoforms in cultured anterior pituitary cells,
      suggesting the possibility of interconnected regulation at this point. To
      evaluate whether the cell content of PKA protein subunits could be similarly
      altered, the catalytic (C) and regulatory type I (RI) and type II (RII) subunits
      were identified by Western blot analysis using specific immunoaffinity-purified
      antibodies. Activation of PKA by the permeant cyclic adenosine monophosphate
      (cAMP) analogue 8-Br-cAMP induced a dramatic time- and concentration-dependent
      decline of C subunit to a residual level that may represent 10-15% of that in
      untreated cells. The most profound decrease occurred during the first 5 h
      following treatment with 0.5-2 mM analogue (by 65 +/- 14 and 79 +/- 5%,
      respectively). Under identical conditions, RII was increased by about 40% at the
      higher concentrations, while RI increased slightly, but only at low
      concentrations (below 1 mM 8-Br-cAMP), and then gradually decreased. Exposure of
      cells to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) also
      resulted in decreased levels of the PKA C subunit, however, with a different
      concentration-dependent profile. In particular, a decline in PKA C was most
      pronounced (60%) at a low concentration of TPA (10 nM) as compared with the
      concentrations equal to or above 20 nM (40% decrease). TPA at 10 nM also
      depressed notably (by 25%) the level of RII subunit, but higher concentrations
      were essentially ineffective, although a slight and statistically not significant
      elevation of the cell subunit content was observed as for RI. Simultaneous
      activation of both PKA and PKC pathways resulted in further depletion of PKA C
      and an important loss (50%) of RII, a subunit which was enhanced by the
      activation of either system alone. Finally, gonadotropin-releasing hormone, a
      neuropeptide that has the potentiality to activate both PKA and PKC signaling in
      gonadotropes, was able to alter PKA subunit cell content: PKA C was significantly
      reduced at either a subliminal (0.1 nM) or maximal (10 nM) concentration, whereas
      RII increased at the low concentration and decreased at the high concentration.
      In conclusion, these data demonstrate that the pituitary cell contents of RI,
      RII, and C subunits of PKA are regulated under the activation of PKA itself as
      well as PKC in a manner that can exhibit further alteration when both systems
      come simultaneously into play. Changes in the PKA subunit levels in certain cases
      may correlate with a variation of the mRNAs suggesting multiple control
      mechanisms, including an alteration of gene expression and changes in subunit
      degradation, synthesis, and/or turnover. These data, together with those obtained
      in the presence of gonadotropin-releasing hormone, provide further support for a
      hormonally induced interplay between PKA and PKC signaling pathways at the
      crucial level of PKA in the pituitary gland including gonadotropes.

PMID- 8559284
TI  - Immunocytochemical localization of basic fibroblast growth factor in the human
      pituitary gland.
AB  - The immunocytochemical localization of basic fibroblast growth factor (bFGF) was
      studied in the human pituitary gland using a polyclonal antibody against fraction
      1-24 of bovine recombinant bFGF. From a technical perspective, methacarn-fixed
      tissues were associated with a better preservation of bFGF immunoreactivity.
      Basic FGF-immunopositive glandular secretory cells were detected from the fetal
      period to adulthood in the pars distalis. No bFGF-positive cells were found in
      the neural lobe, basophil invasion areas, pars tuberalis or the walls of the
      pituitary cleft in the fetal pituitaries where this area was available.
      Endothelial cells and the axons of the neurohypophysis appeared weakly
      immunopositive or immunonegative depending on the fixative. According to their
      morphology, distribution, and the serial section analysis with all the pituitary
      hormones and vimentin, a folliculostellate cell marker, we conclude that bFGF
      positive cells appear to be somatotropes. These results are consistent with the
      interpretation that bFGF plays a paracrine role in the modulation of the
      synthesis and secretion of various pituitary hormones.

PMID- 8559285
TI  - Dexamethasone suppresses the release of prolactin from the rat anterior pituitary
      gland by lipocortin 1 dependent and independent mechanisms.
AB  - Glucocorticoids have been shown repeatedly to inhibit the release of prolactin
      (PRL) in the rat but their site and mode of action is unknown. In the present
      study, we used an in vitro model to examine the requirement for protein synthesis
      for dexamethasone to suppress the release of immunoreactive (ir)-PRL release from
      the rat pituitary gland. In addition we have performed a series of in vitro and
      in vivo experiments to investigate the potential role in this regard of
      lipocortin 1 (LC1), a protein shown previously not only to mediate aspects of the
      anti-inflammatory and anti-proliferative actions of the glucocorticoids but also
      to contribute to the regulatory actions of the steroids in the brain
      neuroendocrine system. In vitro, the release of ir-PRL from rat anterior
      pituitary tissue initiated by submaximal concentrations of VIP (10 nM). TRH (10
      nM) or the adenyl cyclase activator forskolin (100 microM) was reduced
      significantly (p < 0.01) by preincubation (2 h) of the tissue with dexamethasone
      (0.1 microM). By contrast, ir-PRL release evoked by a submaximal concentration of
      the L-Ca2+ channel opener BAY K8644 (10 microM) was unaffected by the steroid
      although readily antagonised (p < 0.01) by nifedipine (1-100 microM). Exposure of
      the pituitary tissue to dexamethasone (0.1 microM) also caused a pronounced and
      highly significant increase in de novo protein synthesis, as assessed by the
      incorporation of 14C-lysine into the tissue (p < 0.001). This response was
      reduced markedly by the inclusion of the RNA and protein synthesis inhibitors,
      actinomycin-D (0.5 micrograms/ml) or cycloheximide (1.0 micrograms/ml), in the
      incubation medium (p < 0.001), both of which also effectively abrogated (p <
      0.01) the dexamethasone-induced inhibition of the release of ir-PRL evoked by
      TRH. VIP and forskolin. Lipocortin I was readily detectable by Western blotting
      in protein extracts of freshly excised anterior pituitary tissue: a small
      proportion of the protein was found to be attached to the outer surface of the
      cells where it was retained by a Ca(2+)-dependent mechanism. Exposure of the
      tissue in vitro to dexamethasone (0.1 microM) or corticosterone (0.1 microM) but
      not 17 beta-oestradiol (0.1 microM) caused a pronounced increase in the amount of
      LC1 attached to the outer surface of the cells and concomitant decrease in the
      LC1 content of the intracellular LC1 pool. Addition of an N-terminal LC1
      fragment. LC11-188 (10 pg-10 ng/ml), to the incubation medium reduced
      significantly (p < 0.01) the increases in ir-PRL release induced in vitro by VIP
      (10 nM) and forskolin (100 microM). By contrast, at all concentrations tested.
      LC11-188 (10 pg-10 ng/ml) failed to influence (p < 0.05) the highly significant
      (p < 0.01) ir-PRL response to TRH (10 nM). Similarly, the inhibitory actions of
      dexamethasone (0.1 microM) on the release of ir-PRL induced by VIP (10 nM) or
      forskolin (100 microM) but not by TRH (10 nM) were substantially reversed (p <
      0.01) by a specific monoclonal anti-LC1 antibody while an isotype-matched control
      antibody was without effect. In vivo, rats pretreated with either a polyclonal
      anti LC1 antiserum (anti-LC1 pAb, 1 ml/day s.c. for 2 days) or a corresponding
      volume of non-immune sheep serum (NSS) responded to stress (laparotomy under
      ether anaesthesia) with significant (p < 0.05) increases in the serum ir-PRL
      concentration. In the NSS-treated group, the ir-PRL response to stress was
      effectively inhibited by dexamethasone (100 micrograms/kg i.p.) which had no
      effect on the pre-stress serum ir-PRL concentration. By contrast, in rats
      pretreated with anti-LC1 pAb dexamethasone failed to block the stress-induced
      release of ir-PRL. The results show clearly that the inhibitory actions of
      dexamethasone on PRL release are dependent on de novo protein synthesis and
      provide novel evidence for the involvement of both LC1-dependent and LC1
      independent mechanisms.

PMID- 8559286
TI  - Intracranial cavernous malformations: lesion behavior and management strategies.
AB  - Intracranial cavernous malformations are vascular anomalies consisting of
      endothelium-lined caverns filled with blood at various stages of thrombosis and
      organization and separated by a collagenous stroma devoid of mature vessel wall
      elements. They occur in an estimated 0.45 to 0.9% of the population, with male
      and female patients equally affected and all ages represented. They commonly
      manifest as seizures, gross intracranial hemorrhage, and focal neurological
      deficits. Lesions are frequently multiple in the same patient, and 10 to 30% are
      associated with familial clustering. Several reports have documented a dynamic
      clinical-radiological lesion behavior with de novo lesion genesis, intralesional
      and perilesional hemorrhage, and corresponding fluctuations in lesion size.
      Hemorrhagic risk and neurological disability seem to be related to multiple
      factors, including lesion location, age, gender, state of reproductive cycle, and
      previous hemorrhage. Lesions may behave aggressively with repetitive hemorrhages
      and cumulative disability or may remain quiescent for many years. Management
      strategies include expectant follow-up in patients with asymptomatic or
      inaccessible lesions, excision of symptomatic and accessible lesions, and
      radiosurgery of progressively symptomatic lesions in inoperable locations.
      Relevant disease-specific outcome parameters are proposed to guide clinical
      decisions and future research. Prospective, stratified, hypothesis-driven studies
      using rigorous epidemiological methods must be undertaken to delineate patient
      and lesion factors influencing clinical aggressiveness. Biological studies are
      essential to uncover strategies to predict and modify lesion behavior.

PMID- 8559287
TI  - The safety and effectiveness of brain arteriovenous malformation embolization
      using acrylic and particles: the experiences of a single institution.
AB  - The purpose of this article is to report on the safety and effectiveness of brain
      arteriovenous malformation (AVM) embolization for two series of patients, of
      which one was treated with particulate embolization and the other with acrylic
      embolization. Sixty-five consecutive patients from embolization logs and patient
      records from 1988 to 1993 were reviewed. AVMs were routinely treated with
      particulate embolization early in the review (1988-1991), and after a transition
      period, the technique was changed to acrylic embolization for the remainder of
      the study period (1992-1993). All patients were treated with the ultimate goal of
      complete AVM obliteration. AVMs were embolized and resected, if possible, and if
      unresectable, they were reduced in size with embolization and radiated. The
      course of treatment for each patient was reviewed. The effectiveness at the end
      of treatment was analyzed for the ability to resect the AVM and, if unresectable,
      the ability to reduce the AVM to radiation size. Additionally, the safety of each
      embolization technique was evaluated in the context of comprehensive care, in
      terms of the safety of the procedure itself, the surgical resection after
      embolization, and the outcome at the end of comprehensive treatment. This article
      outlines the safety and effectiveness of acrylic and particulate embolization at
      a single institution. The ability to surgically resect an AVM after embolization
      and to reduce nidus size with acrylic was at least comparable with that with
      particulate embolization. Comprehensive complication rates were lower after
      acrylic embolization and were heavily influenced by a decreased number of
      surgical complications in the acrylic series. These data support the need to
      conduct a randomized prospective clinical trial to compare the relative safety
      and effectiveness of the two methods of embolization.

PMID- 8559288
TI  - Functional magnetic resonance imaging as a management tool for cerebral
      arteriovenous malformations.
AB  - The location of eloquent cortex, such as the motor strip, the visual cortex, or
      Broca's area, may be difficult to predict even with multiprojectional magnetic
      resonance imaging (MRI). Distortion and displacement of this cortex may occur
      with a congenital lesion, such as an arteriovenous malformation, or by an
      acquired disease, such as a neoplasm. A desire to avoid damaging these eloquent
      areas by conventional surgery, radiosurgery, or endovascular surgery makes their
      accurate identification an important part of the pretherapeutic planning process.
      Blood oxygen level dependent functional MRI is a technique that uses the local
      increase of oxyhemoglobin concentration in the patient that occurs as a result of
      the increase in flow rate and blood volume in eloquent cortex undergoing
      stimulation from, for example, flashing lights, hand movements, or speech. We
      have used the blood oxygen level dependent technique to localize eloquent cortex
      relative to arteriovenous malformations and tumors. Using a 4.0-T magnetic
      resonance (MR) system, there is a sufficiently high degree of spatial resolution
      of the MR signal intensity changes during stimulation to allow the identification
      of eloquent cortex. Alternative, non-MR, invasive techniques for functional
      localization include electrocorticography and stimulation from subdural grids and
      strips. Noninvasive, non-MR technologies, such as positron emission tomography
      and magnetoencephalography, can also provide functional localization of eloquent
      cortex. However, the perfection of functional MRI at the 1.5-T field strength and
      the large number of such MR systems in operation mean that a highly accurate
      cerebral cortical localization technique can be available to most neuroscientists
      without the need to purchase alternative expensive technology.

PMID- 8559289
TI  - Intracranial aneurysm surgery in the 8th and 9th decades of life: impact on
      population-based management outcome.
AB  - Thirteen percent of Sweden's population (8.6 million) is aged 70 years or older,
      and this percentage is expected to increase over the coming decades. We have
      traced every diagnosed case of subarachnoid hemorrhage in patients older than 70
      years in a well-defined catchment population of 953,000 individuals. The age
      specific incidence for this group was 16 per 100,000 individuals per year,
      corresponding to 2.3 per 100,000 inhabitants per year. In most recent population
      based surgical series on ruptured aneurysms, few patients in this age group are
      included, corresponding to only 20 to 25% of the actual number of patients, as
      shown in this study. Surgery is, in many cases, refused to the "elderly" because
      of age. However, patients who are neurologically intact after the bleed and who
      are without severe intercurrent diseases are potential candidates for surgical
      treatment. In our series, surgery yielded good results in two-thirds of 76
      patients aged 70 to 74 years who returned to independent living in good mental
      condition. Among matched patients being refused surgery because of age, 75%
      suffered morbidity and mortality, with more than half of the patients having died
      within the 1st 3 months. When calculated for the entire population of Sweden, our
      data show that a 14% increase in the number of individuals achieving complete
      remedy from aneurysm rupture each year can be expected with more active therapy
      among the elderly. Most of these patients are between 70 and 74 years old. In the
      9th decade of life, aneurysm surgery probably best remains an exception.

PMID- 8559290
TI  - Familial cerebral aneurysms: a study of 13 families.
AB  - Despite the recent interest in familial cerebral aneurysms, the epidemiology,
      natural history, pattern of inheritance, screening of asymptomatic relatives, and
      the search for a biochemical marker remain problematic. To assess these issues,
      we report the results of our prospective study of 30 patients with 38 aneurysms
      (27 ruptured) and of the angiographic screening of asymptomatic relatives, all
      from 13 families seen consecutively since 1986. Women were over-represented
      (77%), and patients with multiple aneurysms (17%) were under-represented,
      compared with sporadic cases. Only 16% of the aneurysms were at the anterior
      communicating artery. Aneurysms occurred at the same or at the mirror site in 10
      of 16 siblings (62%) and in 50% of mother-daughter pairs versus 20% for randomly
      selected, sporadic aneurysm patients. Rupture occurred in the same decade in 10
      of 12 siblings (83%) versus the expected 21% for randomly selected, sporadic
      aneurysms. The average age at rupture was 47.2 years, and 60% of patients with a
      ruptured aneurysm were 50 years of age or younger. Seventy percent of patients
      died or were disabled from aneurysmal rupture. Screening of 41 individuals,
      including 2 dizygous twins, identified 1 aneurysm and 2 infundibula. A specific
      pattern of inheritance could not be ascertained from the pedigrees. The presence
      of an aneurysm was not associated with a specific human leukocyte antigen
      haplotype or antigen, and collagen Type III was qualitatively and quantitatively
      normal. Until a biological marker is identified, angiographic screening by intra
      arterial digital subtraction or magnetic resonance angiography remains the only
      way to identify patients at risk of harboring a familial cerebral aneurysm.

PMID- 8559291
TI  - Early treatment of ruptured aneurysms with Guglielmi detachable coils: effect on
      subsequent bleeding.
AB  - The major causes of mortality and morbidity in patients surviving the rupture of
      a saccular aneurysm are subsequent bleeding and vasospasm. The purpose of this
      study was to evaluate the influence of early treatment of ruptured aneurysms with
      Guglielmi detachable coils on the incidence of subsequent bleeding. Thirteen
      patients were treated within 72 hours of initial aneurysm rupture with Guglielmi
      detachable coils. Excluding three patients who died 2, 4, and 12 weeks after
      initial hemorrhage, all others have been followed up for intervals between 6 and
      36 months (mean, 16 mo). None of these have had either clinical or radiographic
      evidence of subsequent bleeding. Assuming that there is a 30% incidence of
      subsequent bleeding in conservatively (nonsurgically) treated patients, the 0%
      subsequent bleed rate observed in this subgroup was significant at a P value of
      0.01. Only one procedure-related complication occurred in this series, and 9 of
      13 (69%) aneurysms were 100% occluded at the time of initial treatment. All
      aneurysms were at least 90% occluded at the end of initial treatment. In addition
      to reducing the risk of subsequent bleeding, early treatment facilitated the
      institution of an aggressive approach for management of both vasospasm and
      increased intracranial pressure. Patient outcome, as measured by the Glasgow
      Outcome Scale, was good in 9 of 13 (69%), poor in 1 of 13 (8%), and death in 3 of
      13 (23%) patients. The results of this study suggest that early Guglielmi
      detachable coil treatment of ruptured aneurysms may be effective in reducing the
      incidence of subsequent bleeding and can be performed with a low incidence of
      complications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559292
TI  - Delayed onset of hyponatremia after transsphenoidal surgery for pituitary
      adenomas.
AB  - Hyponatremia is rarely reported as a delayed complication of transsphenoidal
      resection of pituitary adenoma. Usually attributed to the syndrome of
      inappropriate secretion of antidiuretic hormone (SIADH), hyponatremia causes
      nonspecific symptoms, often after hospital discharge. To clarify the frequency,
      presentation, and outcome of this poorly understood complication, we reviewed our
      database of 2297 patients who underwent transsphenoidal pituitary surgery between
      February 1971 and June 1993. Of 53 patients (2.3%) treated for symptomatic
      hyponatremia, 11 were excluded (2 received arginine vasopressin within 24 hours,
      1 had untreated hypothyroidism, 4 had untreated adrenal insufficiency, and 4 had
      incomplete records). The remaining 42 patients (1.8%), 11 men and 31 women aged
      21 to 79 years, presented 4 to 13 days (mean, 8 d) postoperatively with nausea
      and vomiting (20 patients), headache (18 patients), malaise (12 patients),
      dizziness (4 patients), anorexia (2 patients), and seizures (1 patient).
      Hyponatremia was unrelated to sex, age, adenoma type, tumor size, or
      glucocorticoid tapering. Although the clinical picture in our patients is
      consistent with SIADH, this was not supported by the antidiuretic hormone levels,
      which were normal or low-normal in the two patients in whom they were measured,
      suggesting the possibility that low serum sodium may not reflect SIADH. In all
      patients, hyponatremia resolved within 6 days (mean, 2 d); treatment consisted of
      salt replacement and mild fluid restriction in 37 patients and fluid restriction
      only in 4 (treatment unknown in 1). Delayed hyponatremia after transsphenoidal
      resection of pituitary adenoma is not as rare as previously thought, nor is it
      necessarily associated with SIADH or with hypoadrenalism during glucocorticoid
      tapering.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559293
TI  - Intracranial ependymomas of childhood: long-term outcome and prognostic factors.
AB  - A detailed outcome analysis was performed on 40 children with intracranial
      ependymomas treated at our institution between 1975 and 1993 to identify those
      factors that were predictive of overall and progression-free survival. Three
      patients (7.5%) who were treated in the first 5 years of the study died within 3
      months of surgery and were excluded from further outcome assessments. Eight (22%)
      of the 37 patients who survived the perioperative period had evidence of
      leptomeningeal dissemination at presentation, on the basis of either imaging
      (three children) and/or cytological (six children) results. The 5- and 10-year
      progression-free survival rates among these 37 patients were 45.1 and 36.1%,
      respectively; overall survival rates were 57.1 and 45.0%, respectively. The site
      of progression was local in 17 of 19 patients with progressive disease. Three
      factors were found to have a significant association (P < or = 0.05) with the
      outcome on both univariate and multivariate analyses: 1) the extent of the
      resection, 2) the age of the patient at diagnosis, and 3) the duration of the
      symptoms before diagnosis. The 5-year progression-free and overall survivals were
      8.9 and 22%, respectively, among patients who had evidence of residual disease on
      postoperative imaging studies, compared with 68 and 80% rates among patients with
      no apparent residual disease (P = 0.0001 and P < 0.0001, respectively). Patients
      younger than 3 years fared significantly worse than older children (5-year
      progression-free and overall survival rates of 12 and 22%, respectively, in the
      younger children versus 60 and 75% in older children (P = 0.003 and P = 0.01,
      respectively). In addition, patients with a duration of symptoms before diagnosis
      of < 1 month had a worse outcome than those with a more protracted course (5-year
      progression-free and overall survival rates of 33 and 33%, respectively, versus
      rates of 53 and 64%, respectively (P = 0.02 for both). Neither the finding of
      evidence for dissemination at presentation nor the detection of anaplastic
      histological features (e.g., dense cellularity or high numbers of mitoses) were
      associated with a significantly worse outcome in this series. The combination of
      variables that had the strongest association with both favorable and unfavorable
      outcomes was the combination of the age of the patient and the resection extent.
      Only 2 of 17 patients older than 3 years with gross total resections have died,
      whereas 13 of 20 children who were either younger than 3 years or had
      radiologically incomplete resections have died (P < 0.0001).(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8559294
TI  - Differences between ventricular and lumbar cerebrospinal fluid in hydrocephalus
      secondary to cysticercosis.
AB  - We studied ventricular and lumbar cerebrospinal fluid (CSF) in 16 patients with
      hydrocephalus secondary to meningeal cysticercosis, and samples were taken at the
      time of the surgical implantation of a ventricular shunt. All lumbar CSF samples
      revealed raised cell counts (mean, 72 +/- 28/mm3) and protein counts (mean, 78 +/
      12 mg/dl), as well as positive immune reactions to cysticerci antigens. In
      contrast, 50% of the ventricular CSF samples exhibited cell and protein counts
      within normal limits and five showed negative immune reactions to cysticerci
      antigens. Ample differences between ventricular and lumbar CSF were also observed
      in the contents of glucose and immunoglobulins G, A, and M. The biochemical and
      immunological composition of the CSF varied greatly along the cerebrospinal axis
      in patients with chronic arachnoiditis caused by cysticercosis. Our findings
      further support the premise of the subarachnoid space as an immunologically
      active substratum and provide information to explain the frequent occlusion of
      ventricular shunts in patients with hydrocephalus secondary to inflammatory
      disorders of the subarachnoid space.

PMID- 8559295
TI  - Surgical indication and results of foramen magnum decompression versus
      syringosubarachnoid shunting for syringomyelia associated with Chiari I
      malformation.
AB  - Several surgical procedures have been used for the treatment of syringomyelia
      associated with Chiari I malformation at our institute. The purpose of this
      article is to evaluate the results of two major surgical procedures, foramen
      magnum decompression (FMD) and syringosubarachnoid (SS) shunting. The series
      consisted of 70 patients with syringomyelia associated with Chiari I malformation
      who were surgically treated. Their ages ranged from 3 to 59 years (median, 29.4
      yr). FMD was performed on 33 patients, and SS shunting was performed on 37
      patients. The follow-up period ranged from 6 months to 12.5 years, with a mean of
      60 months. The clinical and radiological outcomes were analyzed comparing the two
      groups. We principally performed FMD in patients with symptoms of Chiari I
      malformation and/or a small syrinx. We prefer to use SS shunting in patients with
      large syringes. Postoperative magnetic resonance imaging demonstrated that the
      syrinx had collapsed or decreased in size in 94% of the patients who underwent
      FMD and in 100% of the patients who underwent SS shunting. Neurological
      improvements were observed in 82% and in 97% of the patients who underwent FMD
      and SS shunting, respectively. In particular, the relief of pain was more fully
      achieved after SS shunting than after FMD. The average time for the syrinx to
      collapse was 6.3 weeks after surgery in the FMD group and 1.8 weeks in the SS
      shunting group. These results indicate that clinical symptoms and radiological
      findings improved much more quickly in the SS shunting group than in the FMD
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559296
TI  - Outcome after stereotactic thalamotomy for parkinsonian, essential, and other
      types of tremor.
AB  - A better understanding of the mechanisms underlying movement disorders, coupled
      with refinements in surgical technique, has led to a resurgence of interest in
      the surgical treatment of patients with tremor. We retrospectively analyzed the
      outcomes of 60 patients (62 patient sides) with medically intractable tremor who
      underwent stereotactic thalamotomy. Of these 60 patients, 42 had Parkinson's
      disease (of whom 2 patients underwent bilateral surgery for a total of 44 patient
      sides), 6 had essential tremor, 6 had cerebellar tremor, and 6 had post-traumatic
      tremor. The patients received follow-up for as long as 13 years (mean, 53.4 mo)
      after their operations. At the most recent follow-up visit, 86% of the patients
      with Parkinson's disease, 83% of the patients with essential tremor, 67% of the
      patients with cerebellar tremor, and 50% of the patients with post-traumatic
      tremor had cessation of or moderate-to-marked improvement in their contralateral
      tremor, with a concomitant improvement in function. The mean daily dose of
      levodopa for those patients preoperatively taking levodopa (n = 35) was reduced
      by approximately 156 mg at a mean of 53.4 months after thalamotomy. Immediate
      postoperative complications were common, occurring in 58% of patients. The most
      common complications were contralateral weakness (34%), dysarthria (29%), and
      confusion (23%). These complications generally resolved rapidly during the
      postoperative period.

PMID- 8559297
TI  - C1-C2 posterior cervical fusion: long-term evaluation of results and efficacy.
AB  - Posterior wiring techniques are the most commonly used methods of achieving C1-C2
      arthrodesis. Recently, transarticular screw fixation and interlaminar clamping
      have been advocated to achieve more secure fixation. A retrospective review of
      patients undergoing C1-C2 fusion for nonneoplastic disease was undertaken at the
      University of Toronto Hospital, with the aim of determining the long-term outcome
      of the selected procedures. Thirty-two patients underwent 36 procedures from 1986
      to 1992, with a mean follow-up of 4.7 +/- 2.2 years (range, 2.0-8.0 yr). The most
      common disease processes were odontoid fracture (18 patients), transverse
      atlantal ligament injury (5 patients), os odontoideum (5 patients), and
      rheumatoid C1-C2 instability (3 patients). Thirty-one Gallie fusions, one Brooks
      Jenkins fusion, two transarticular screw fusions, and two Halifax clamp
      applications were performed. Six (19%) of Gallie/Brooks-Jenkins fusions failed.
      These occurred with os odontoideum (three patients), Type II odontoid fracture
      (two patients), and transverse atlantal ligament injury (one patient). All
      transarticular screw and Halifax clamp procedures resulted in successful fusions.
      Two procedures (6%) resulted in new neurological deficit; both of these patients
      underwent posterior wiring for os odontoideum. This study suggests that Type II
      odontoid fractures may be successfully managed by a posterior wiring technique
      alone. Rheumatoid C1-C2 instability may be managed by posterior wiring
      supplemented with halo immobilization. Transarticular screw fixation has several
      potential advantages as a technique for C1-C2 arthrodesis and, in particular, may
      be appropriate for os odontoideum that had a high failure rate (75%) with
      conventional posterior wiring, even when this was supplemented with halo bracing.

PMID- 8559298
TI  - Functional image-guided neurosurgical simulation system using computerized three
      dimensional graphics and dipole tracing.
AB  - This report describes a preoperative simulation and intraoperative localization
      system for use with three-dimensional functional images in intracranial surgery.
      The system, which produces three-dimensional functional images by superimposition
      of the generators of somatosensory evoked potentials derived from dipole tracing,
      was applied in the preoperative localization of central sulci in 12 patients with
      intracranial disorders. The preoperative localization of central sulci was
      assessed by intraoperative cortical recording of somatosensory evoked potentials
      in three patients. In six patients, three-dimensional computer graphics were
      reconstructed from magnetic resonance images and allowed visualization of the
      lesions through the semitransparent views of the scalp surface and the brain. The
      three-dimensional functional images were created by superimposing the generators
      of somatosensory evoked potentials on three-dimensional computer graphics. This
      combined technique provided preoperative data regarding the three-dimensional
      relationship between the sensorimotor cortex and the lesions. We also developed a
      three-dimensional digitizer that incorporates a mechanical arm and a laser
      pointer for use in integrating information obtained in the preoperative
      simulation into the surgical field. Intraoperative localization can be performed
      in real time on the three-dimensional computer graphics in combination with the
      functional images created from dipole tracing. This system was applied in five
      patients who underwent surgical brain tumor resections with minimal damage to the
      normal brain tissue. The use of this system for stereotactic craniotomy increased
      the safety of the surgery by affording preoperative simulation and intraoperative
      localization with the three-dimensional functional images. Two illustrative case
      reports are presented.

PMID- 8559299
TI  - The anterior cervical approach to the cervicothoracic junction.
AB  - To reach the upper thoracic vertebrae, a number of extensive approaches have been
      proposed combining thoracotomy, sternotomy, or clavicle resection with anterior
      dissection into the superior mediastinum. We present a simple anterior cervical
      approach for patients with disease limited to one vertebral level, in which
      midline ventral decompression is the goal of surgery. Regardless of the anterior
      approach used, the caudal extent of exposure is limited to T3 by the great
      vessels of the mediastinum, whereas the angle of the approach to the
      cervicothoracic junction is dictated by the manubrium. In the anterior cervical
      approach, lateral exposure to the uncovertebral joints is easily achieved. Five
      patients are reviewed in whom this anterior cervical approach was used at the
      first or second thoracic level. Decompression and instrumentation resulting in
      neurological improvement and axial stability were achieved in all five patients.
      The surgical anatomy of the cervicothoracic junction is reviewed with attention
      to the recurrent laryngeal nerves and the thoracic duct as they relate to the
      side of approach chosen.

PMID- 8559300
TI  - A comparison of fluoroscopy and computed tomography-derived volumetric multiple
      exposure transmission holography for the guidance of lumbar pedicle screw
      insertion.
AB  - Holographic technology has recently been modified in such a manner that it may
      now provide clinical use. It allows the visualization of complex structures in
      three dimensions and permits clinician interaction with the image, which, in
      turn, provides significant additional geometric and anatomic information. To
      objectively assess the potential clinical applicability of holography in pedicle
      screw placement, we studied 11 elderly human cadavers. All of the cadavers, each
      of which showed significant degenerative disease of the lumbar spine, underwent
      thin-section computed tomographic scans of the lumbar spine. The acquired digital
      information was processed, and volumetric multiple exposure transmission
      holographic images were rendered. Pedicle screws were passed into anatomically
      acceptable and radiographically visualized L3-L5 pedicles in each cadaver, half
      using fluoroscopic guidance and half using holographic guidance alone. The
      accuracy of screw placement was objectively assessed by a three-point grading
      scale. The total score for the placement of each pedicle screw was determined by
      both trajectory (location within the pedicle) and accuracy (containment within
      the vertebral body) of screw tip placement parameters. Three points were possible
      for each screw placed. Screw placement in the last six cadavers was individually
      timed for each technique, and fluoroscopic time was also recorded. Each technique
      was used on 27 pedicles. The total score for fluoroscopic screw placement was 71
      (71 of a possible 81; 88%) and for holographic screw placement was 74 (74 of a
      possible 81; 91%). In the last six cadavers, the screw placement time (per
      cadaver) was 8 minutes for fluoroscopic placement and 3.6 minutes for holographic
      placement. Fluoroscopic time averaged 1.9 minutes per cadaver.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8559301
TI  - Stereotactic ventrolateral thalamotomy: is ventriculography necessary?
AB  - In the computed tomography/magnetic resonance imaging (CT/MRI) era, the need for
      ventriculography to perform ventrolateral thalamotomy accurately has been
      debated. We retrospectively compared CT/MRI-derived coordinates for ventrolateral
      thalamotomy with the final lesion coordinates that were determined by
      ventriculography and microelectrode recording in 74 thalamotomies performed from
      1984 to 1994. The median three-dimensional distance between the CT/MRI-derived
      loci and the ventriculography/microelectrode loci was 4.7 mm (range, 1.0-11.7
      mm). The techniques correlated least along the Y axis (median, -0.3 mm; range, 
      8.2 to 8.0 mm). Correlation along the X axis was most consistent (median, 0.5 mm;
      range, -4.2 to 5.0 mm). Since 1990, the CT/MRI-derived coordinates have been
      generated by a multimodality correlative imaging technique (MCIT). A comparison
      of thalamotomies performed with and without the MCIT revealed a significant
      improvement in the correlation of CT/MRI- and ventriculography/microelectrode
      derived coordinates when the MCIT was employed. The greatest improvement was
      noted along the Y axis where the median absolute difference was reduced from 4.0
      to 1.8 mm (P = 0.0001). The result was a statistically significant reduction in
      the median three-dimensional distance from 5.6 to 3.7 mm (P = 0.0007). The
      authors conclude that thalamotomies can be safely and effectively performed
      without ventriculography when the MCIT is employed and supported by
      neurophysiological monitoring.

PMID- 8559302
TI  - The potential role of basic fibroblast growth factor in the transformation of
      cultured primary human fetal astrocytes and the proliferation of human glioma (U
      87) cells.
AB  - Basic fibroblast growth factor (bFGF) is a potent stimulator of angiogenesis,
      proliferation, and invasion in human gliomas. To test the hypothesis that bFGF is
      important in the development of the malignant phenotype of human gliomas, bFGF
      expression was prospectively modulated in primary human fetal astrocytes and in
      an established human glioma cell line. Fetal astrocytes were transfected with a
      vector expressing bFGF modified by the addition of a secretory signal peptide
      sequence. Two of these bFGF astrocyte clones examined in vitro demonstrated
      anchorage-independent growth, loss of contact inhibition, and decreased glial
      fibrillary acidic protein immunoreactivity, changes consistent with cellular
      transformation. To analyze the inhibition of bFGF expression, phosphorothioated
      bFGF antisense oligodeoxynucleotides were added to cultures of the U-87 human
      glioma cell line. The U-87 cell proliferation was inhibited to 70.6 +/- 0.4% of
      control at 10 mumol/L and to 53.2 +/- 5.6% of control at 20 mumol/L (P < 0.05).
      Both the 7.0- and 4.0-kilobase bFGF messenger ribonucleic acid transcripts were
      reduced after exposure to the antisense oligodeoxynucleotide, and cell-associated
      bFGF protein was reduced by 44%. The sense oligodeoxynucleotide, a negative
      control, failed to inhibit U-87 proliferation. These data support the concept
      that bFGF expression could be a key event in glial tumorigenesis that may be
      necessary for the sustained growth of human gliomas.

PMID- 8559303
TI  - Effects of brain-derived neurotrophic factor on 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-induced parkinsonism in monkeys.
AB  - The effects of intrathecal infusion of brain-derived neurotrophic factor (BDNF)
      were examined in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced
      parkinsonian model in monkeys. Nine Japanese monkeys were divided randomly into
      three groups, an untreated control (n = 3), a BDNF group (n = 3), and a non-BDNF
      group (n = 3). Animals in the BDNF group received continuous intrathecal infusion
      of 10 ml of cell culture medium containing 10 micrograms of BDNF protein; the non
      BDNF group received intrathecal infusion of the same culture medium without BDNF.
      To induce parkinsonian syndromes, a total of 1 mg/kg 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine was administered intravenously to each monkey in both the BDNF
      and non-BDNF groups. The neurological signs in the monkeys were monitored for 2
      weeks and were scored according to the monkey parkinsonism rating scale;
      histological changes in the substantia nigra were evaluated after the 2-week
      observation period. The BDNF-treated animals remained asymptomatic during the 1st
      week and showed mild parkinsonism during the 2nd week, whereas the non-BDNF group
      showed typical parkinsonian syndrome during the 1st week, with deterioration in
      the 2nd week. Histological damage in the substantia nigra correlated well with
      the clinical features. Severe neuronal cell loss in the substantia nigra was
      observed in animals with severe parkinsonism (those in the non-BDNF group),
      whereas significantly less damage was observed in this region in the BDNF
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559304
TI  - Focal cerebral ischemia during anesthesia with etomidate, isoflurane, or
      thiopental: a comparison of the extent of cerebral injury.
AB  - An investigation was performed to compare the cerebral protective properties of
      etomidate, isoflurane, and thiopental. In separate groups of spontaneously
      hypertensive rats, etomidate, isoflurane, or thiopental was administered to
      achieve and maintain burst-suppression of the electroencephalogram (3-5
      bursts/min) for the duration of the experiment. A fourth group received 1.2
      minimal alveolar concentration halothane. All groups underwent 3 hours of middle
      cerebral artery occlusion and then 2 hours of reperfusion. Thereafter, the
      animals were killed and the volume of injured brain was determined by staining
      with 2,3,5-triphenyltetrazolium. Physiological parameters did not differ among
      the four groups during the investigation, with the exception that hemolysis
      occurred in the etomidate group (free hemoglobin levels, approximately 0.4 g.dl
      1). The volume of injured brain in the thiopental group (56 +/- 10 mm3) was
      significantly smaller than that in the halothane control group (99 +/- 13 mm3).
      The volumes of injured brain in the etomidate and isoflurane groups (145 +/- 11
      mm3 and 139 +/- 14 mm3, respectively) were significantly larger than those in the
      control and thiopental groups. We speculate that the apparently detrimental
      effect of etomidate may be the result of the binding of nitric oxide of cerebral
      endothelial origin by the iron component of free hemoglobin. Intracranial
      pressure was not recorded, and in the isoflurane group, there may have been
      adverse effects on cerebral perfusion pressure associated with vasodilation
      caused by high concentrations of isoflurane. The results are consistent with a
      protective effect by barbiturates.

PMID- 8559305
TI  - Interrupted arterial occlusion reduces ischemic damage in a focal cerebral
      ischemia model of rats.
AB  - It is generally thought by neurosurgeons that when temporary clipping of a major
      cerebral vessel is necessary during aneurysm surgery, repeated short periods of
      cerebral ischemia are safer for the brain than a single long episode. This study
      was performed to investigate whether repetitive short episodes of cerebral
      ischemia would alter the resulting brain injury as compared with a single long
      period of ischemia in a rat model for focal cerebral ischemia. Middle cerebral
      artery occlusion and reperfusion were performed by the intraluminal thread
      technique. The experimental design consisted of a single 90-minute occlusion
      period in the continuous ischemia group versus three 30-minute occlusion periods
      with 15-minute reperfusion periods in the repetitive group. Local cerebral blood
      flow was measured by the hydrogen clearance technique. During the ischemic
      period, local cerebral blood flow values significantly decreased in both the
      continuous and the repetitive groups. Cerebral blood flow restoration was
      demonstrated after each episode of reperfusion in both groups. The neurological
      status scores 2 hours after surgery in the rats subjected to repetitive insults
      were significantly better compared with those in the rats of the continuous
      ischemia group. However, the scores on Days 1, 3, and 7 did not show a
      significantly better difference. The animals were killed 7 days after the
      induction of ischemia for the measurement of the infarction area under the
      microscope. The total area of infarction was significantly reduced (4.05 +/- 4.56
      versus 47.2 +/- 37.3 mm2, P < 0.001) by interruption of the ischemic time
      period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559306
TI  - Tumor necrosis factor-alpha induces p53-dependent apoptosis in rat glioma cells.
AB  - In this study, we demonstrated that tumor necrosis factor (TNF)-alpha inhibited
      the viability of rat glioma (C6) cells and induced apoptosis but did not affect
      the viability of rat newborn brain, mainly astroglial cells. The antitumor
      activity of TNF-alpha against C6 cells was partially inhibited by actinomycin D
      and cycloheximide, suggesting that it is possibly dependent upon new ribonucleic
      acid and protein synthesis. The results of immunoblotting assay demonstrated that
      TNF-alpha decreased the expression of mutant p53 protein but induced the
      expression of wild-type p53 in C6 cells during apoptosis. We suggest that TNF
      alpha may activate the function of wild-type p53 protein by the suppression of
      mutant p53, at least indirectly, and induce p53-dependent apoptosis in glioma
      cells.

PMID- 8559308
TI  - Computer modeling of intracranial saccular and lateral aneurysms for the study of
      their hemodynamics.
AB  - There is strong evidence indicating hemodynamic stress as an underlying cause for
      saccular intracranial aneurysm growth, thrombosis, and/or rupture. We examined
      flow fields encountered in models of cerebral aneurysms having a lateral
      (originating from the side of an artery, not at a branch point) geometric
      configuration. Shear stress and pressure gradients acting on aneurysm walls under
      a variety of flow and geometric conditions were evaluated. For this purpose, a
      two-dimensional finite-element computer model of lateral aneurysms in a steady
      flow state was developed. Three idealized aneurysm shapes were studied, half
      spherical, spherical, and pear-shaped. The ostium width of the cerebral aneurysm,
      relative to the radius of the parent artery and the Reynolds number, were also
      varied. Maximal shear stresses and maximum pressures (for an ostium width of 2
      times the radius of the parent artery) were typically found at the downstream
      site of the ostium, rather than at the dome of the aneurysm. In general, the
      highest shear stresses and the lowest pressures (at the distal portion of the
      ostium) were obtained in the spherical aneurysm, whereas the lowest shear
      stresses and the highest pressures were found in the half-spherical aneurysm. The
      location of maximal stresses (shear and pressure) at the distal region of the
      ostium suggests that growth and/or rupture may well proceed from this point. Such
      findings are in contrast to the commonly held opinion that aneurysm rupture
      occurs at the dome. Careful pathological investigation will need to be performed
      to clarify this finding. The results of this preliminary investigation also
      indicate that the flow field in lateral aneurysms is highly dependent on a number
      of factors related to flow and geometric parameters. Geometry seems to be a
      significant mediator of local magnitudes of stress. Thus, the tendency for growth
      or thrombosis may be influenced by variations in size or shape.

PMID- 8559307
TI  - Combined molecular genetic studies of chromosome 22q and the neurofibromatosis
      type 2 gene in central nervous system tumors.
AB  - Monosomy of chromosome 22 or deletions of 22q have been described in meningiomas
      and astrocytic tumors, the incidence of which is increased in Type 2
      neurofibromatosis. Recently, the gene for neurofibromatosis Type 2 (NF2) has been
      identified at Chromosome 22q12, and a tumor suppression role has been suggested.
      Because there have been only a few studies of the NF2 gene on central nervous
      system tumors other than vestibular schwannomas, we investigated the potential
      role of NF2 as a tumor suppressor gene in a group of sporadic meningiomas and
      astrocytomas. Forty-four tumors (26 meningiomas and 18 astrocytic tumors of
      different grades) were screened for NF2 mutations for the entire 17 exons by the
      polymerase chain reaction-single-strand conformation polymorphism method. In
      addition, 37 tumors and their respective constitutional deoxyribonucleic acid
      were analyzed for loss of heterozygosity of 22q alleles by four polymorphic
      microsatellite markers. Seven inactivating mutations were found in Exons 4, 5, 6,
      and 10 in 7 of 26 (27%) meningiomas, but none were found in astrocytic tumors.
      Altogether, 69% of meningiomas and 20% of astrocytic tumors revealed a loss of
      heterozygosity of 22q markers. All tumors with NF2 mutations showed concurrent
      loss of alleles on 22q, thus fulfilling Knudson's criteria for tumor suppressor
      genes in meningiomas. We conclude that inactivation of the NF2 gene is involved
      in the pathogenesis of a proportion of meningiomas but not in astrocytic tumors.
      Because many meningiomas and some astrocytic tumors had allelic loss of 22q but
      intact NF2, there is a possibility that other tumor suppressor genes exist on 22q
      and may be involved in the pathogenesis of central nervous system tumors.

PMID- 8559309
TI  - Neurosurgery at the University of Florida.
AB  - The significant factors in the development of the neurosurgery program at the
      University of Florida have been the funding for 10 endowed chairs and a Brain
      Institute, the achievement of departmental status in the College of Medicine, the
      collaborative research with a strong Department of Neuroscience, and the strong
      commitment by the faculty to subspecialty neurosurgery and to service in the
      national neurosurgical organizations.

PMID- 8559310
TI  - Phrenology in the science and culture of the 19th century.
AB  - In the last decade of the 18th century, Franz Joseph Gall of Vienna invented a
      combination of physiognomy and brain localization that he originally called
      "craniology" (the science of the head) and later called "organology" (the science
      of the organs of the brain). Between 1800 and 1812, he worked with Johann
      Christoph Spurzheim on a variety of important neuroanatomic studies to support
      this new science. By 1812, when they parted company in Paris, Spurzheim had
      become intrigued with the psychosocial potential of the undertaking, which he
      renamed "phrenology" (the science of the mind). Because a phrenological
      examination (palpation of skull prominences) could provide an analysis of a
      person's strengths and weaknesses, Spurzheim thought that his system could lead
      to personal improvement for everyone, including the laboring classes. He was thus
      a 19th century reformer, generally on the liberal side of the political and
      social spectrum. Spurzheim spread his gospel to Britain through several long
      lecture tours, and phrenology became briefly popular through the efforts of other
      British reformers, especially George Combe. In 1832, Spurzheim came to the United
      States. Three months later, he died in Boston, a martyr to his cause. Phrenology
      then spread widely into American popular culture, encouraged by the
      entrepreneurial efforts of "the phrenological Fowlers" and others like them. By
      1843, the entire Western scientific community rejected organology and phrenology.
      All forms of cerebral localization were lumped with phrenology and similarly
      repudiated. Nonetheless, Gall's organology was the first comprehensive, premodern
      statement of a theory of cerebral localization. The early pioneers of modern
      localization, especially Paul Broca and David Ferrier, were careful to define how
      their theories differed from phrenology, even as they provided the clinical and
      scientific data that confirmed some of its basic tenets.

PMID- 8559311
TI  - Expanding intracerebral hematoma from pituitary adenoma: case report.
AB  - We report the case of a 53-year-old man presenting with a headache of sudden
      onset and blurred vision secondary to hemorrhage from a nonfunctioning pituitary
      adenoma, which had been treated 25 years previously by transcranial surgery and
      postoperative irradiation. The intratumoral and intracerebral hematoma expanded
      to three times its initial size because of a recurrent hemorrhage that occurred
      during a 2-day period while the patient awaited surgery. The mechanisms of
      hematoma expansion and the management strategy in such a case are discussed, and
      a review of the pertinent literature is presented.

PMID- 8559312
TI  - Gonadotropic pituitary carcinoma: case report.
AB  - A 37-year-old man developed multiple intracranial, intraspinal, and general
      metastases from an invasive nonfunctioning pituitary adenoma after surgery and
      radiation therapy. This is the first gonadotropic pituitary carcinoma reported in
      literature.

PMID- 8559313
TI  - Intramedullary spinal cord abscess: case report.
AB  - Intramedullary spinal cord abscesses are rare lesions with a poor prognosis
      unless diagnosed and treated promptly. We report a case of a Nigerian man with
      tuberculous meningitis that was complicated by an intraspinal cord abscess and
      was treated surgically. The literature regarding this uncommon clinical entity is
      reviewed.

PMID- 8559314
TI  - Postsurgical development of dural arteriovenous malformations after transpetrosal
      and transtentorial operations: case report.
AB  - The authors present a case of mixed pial and dural arteriovenous malformations
      (AVMs) in the transverse and the sigmoid sinuses, which developed 2 years after
      the resection of a trigeminal neuroma via the transpetrosal and transtentorial
      approach. To the best of our knowledge, this is the first case of the delayed
      development of dural AVMs after transpetrosal and transtentorial surgery. The
      cause of acquired dural AVMs is discussed, and the potential risk of delayed
      development of dural AVMs after transpetrosal and transtentorial surgery is
      described.

PMID- 8559315
TI  - Spontaneous cerebrospinal fluid fistula through the clivus: report of two cases.
AB  - There have been no previous reports of a spontaneous cerebrospinal fluid fistula
      through the clivus. We present two such cases, describe their management, and
      propose a physiopathological explanation. The pulsating effect of the basilar
      artery in Patient 1 and brisk increases in intracranial pressure through repeated
      Valsalva maneuvers, acting on a congenitally thin bone in Patient 2, seem to be
      the plausible causes for the clival leakage.

PMID- 8559316
TI  - Surgical management of pseudotumor cerebri in pregnancy: case report.
AB  - Little has been written concerning the surgical treatment of pregnant patients
      with pseudotumor cerebri. We present four cases of pregnant women who underwent
      lumboperitoneal shunt placement during pregnancy for progressive visual loss
      despite maximal medical therapy. The intraperitoneal pressure measured during
      surgery was significantly less than the cerebrospinal fluid pressure. Three of
      the four women had marked improvement in their vision after shunting, and one
      required optic nerve sheath decompressions for improvement. All delivered healthy
      babies. Pseudotumor cerebri in pregnant patients with progressive visual loss
      despite medical therapy is surgically treatable, and normal deliveries are
      expected. Therapeutic abortion to limit progression of the disease is not
      indicated.

PMID- 8559317
TI  - Endovascular stent placement for multiple aneurysms of the extracranial internal
      carotid artery: technical case report.
AB  - A patient with multiple extracranial internal carotid artery aneurysms that
      caused cerebral infarction was treated by endovascular placement of a metallic
      stent. Complete disappearance of the aneurysms was angiographically confirmed
      within 15 weeks. Endovascular observation 6 months after the stent placement
      revealed that the endoluminal surface was totally covered by normal endothelium.
      The patient returned to his regular work routine and had no complication or
      neurological deterioration during the 17-month follow-up period.

PMID- 8559318
TI  - Reduction and stabilization without laminectomy for unstable degenerative
      spondylolisthesis: a preliminary report.

PMID- 8559319
TI  - Management of the vertebral artery in excision of extradural tumors of the
      cervical spine.

PMID- 8559320
TI  - Spinal epidural cavernous angioma presenting as a lumbar radiculopathy with
      analysis of magnetic resonance imaging characteristics: case report.

PMID- 8559321
TI  - Cystic meningiomas: a review.

PMID- 8559322
TI  - Glomus jugulare tumor metastatic to the sacrum after high-dose radiation therapy:
      case report.
AB  - A 47-year-old woman with left ear pain and hearing loss was diagnosed with a
      glomus jugulare tumor for which she received radiation therapy as the primary
      treatment. Over a period of 20 years, she developed temporal bone necrosis, brain
      stem calcifications, local tumor recurrence, and eventually metastases to her
      lungs and sacrum. This case underscores the often indolent nature of glomus
      jugulare tumors, the late sequelae of radiation therapy for benign intracranial
      tumors, and the potential of these tumors to metastasize. This patient's history
      suggests that aggressive surgical resection should be considered early for such
      tumors, particularly because radiation treatment does not ablate the tumor. This
      is only the second reported case of a glomus jugulare tumor metastatic to the
      sacrum.

PMID- 8559323
TI  - Split notochord syndrome: case report.
AB  - Split notochord syndrome includes a cleft of the vertebral column associated with
      malformation of the central nervous system. Fourteen cases involving the
      lumbosacral spine have been reported in the literature. We report on a female
      neonate who had intact function of her lower extremities, a posterior midline
      lumbar defect bounded by two complete spinal canals that contained two spinal
      cords. A meningocele, a large bowel fistula, and a mature teratoma protruded
      through the cleft. The baby is doing well after repair of the anomaly and
      placement of a ventriculoperitoneal shunt.

PMID- 8559324
TI  - Diffuse leptomeningeal enhancement, "ivy sign," in magnetic resonance images of
      moyamoya disease in childhood: case report.
AB  - We report three cases of children with moyamoya disease who revealed prominent
      leptomeningeal enhancement on postcontrast magnetic resonance (MR) images. Two of
      the children underwent bilateral extracranial-intracranial bypass operations
      because of ischemic symptoms. During the operations, a profuse pial arterial
      network was observed, which was considered to be the origin of the enhancement.
      The ischemic episodes disappeared after the operations, and the follow-up MR
      images showed marked reduction of the leptomeningeal enhancement. One of the
      three patients had an extracranial-intracranial bypass operation on one side, but
      postoperative MR images have not yet been obtained. We named this finding on
      postcontrast MR images "ivy sign," because it resembles ivy creeping on stones.
      Ivy sign seems to be a unique, characteristic feature of the pial network
      observed in moyamoya disease.

PMID- 8559325
TI  - Endoscopic treatment of a symptomatic pineal cyst: technical case report.
AB  - Symptomatic pineal cysts are rare and typically managed with an open surgical
      approach. We report the successful treatment of a symptomatic pineal cyst using a
      stereotactic endoscopic technique.

PMID- 8559326
TI  - Resection and replacement of the superior sagittal sinus for treatment of a
      parasagittal meningioma: technical case report.
AB  - We report a case of the complete resection of a parasagittal meningioma,
      including an 8-cm length of the superior sagittal sinus and adjacent dura. Flow
      through the sagittal sinus was reestablished through an interposed saphenous vein
      graft. Intraoperative angiography confirmed immediate patency of the graft, as
      did delayed angiography performed at 8 days. Follow-up magnetic resonance
      angiography 9 months after surgery demonstrated continued patency of the graft.
      Sagittal sinus replacement with a vein graft can be safely performed during
      Simpson Grade I resection of parasagittal meningiomas.

PMID- 8559327
TI  - Ultrasonic ventriculostomy stylet.
AB  - I describe my design for a ventriculostomy stylet fitted with a phase array
      ultrasonic imaging device in its tip. Theoretically, this would allow
      identification of the ventricles and their exact location at the bedside, without
      the need for expensive stereotactic equipment. A device such as this could
      potentially facilitate the placement of ventriculostomy catheters in patients
      with small ventricles, and it could even contribute to the education of
      neurosurgery residents. At present, a prototype of the device is being
      manufactured.

PMID- 8559328
TI  - Lectures on the diseases of the nervous system. Jean Martin Charcot. Lectures on
      the localisation of cerebral and spinal diseases. Jean Martin Charcot.

PMID- 8559329
TI  - Embolization with temporary balloon occlusion of the internal carotid artery and
      in vivo proton spectroscopy improves radical removal of petrous-tentorial
      meningioma.

PMID- 8559330
TI  - A randomized trial of intraoperative, intracisternal tissue plasminogen activator
      for the prevention of vasospasm.

PMID- 8559331
TI  - Simple risk predictions for arteriovenous malformation hemorrhage.
AB  - We present a simple risk prediction formula for arteriovenous malformation
      hemorrhage. Natural history studies have shown an annual risk of hemorrhage of 2
      to 4% for patients with brain arteriovenous malformations. Although decision
      analysis programs and biostatistical models are available to predict long-term
      risks of hemorrhage, we hypothesized that there was varying knowledge regarding
      the use of such programs within the general neurosurgical community. To obtain
      information on the current use of risk data, we performed a survey of
      neurosurgeons at national meetings in 1988 and 1994. Neurosurgeons were asked to
      define the risk for arteriovenous malformation hemorrhage in the young adult
      patient over a 20- to 30-year period, given a 3 or 4% annual risk of hemorrhage.
      A wide range of answers was obtained (1-100% risk), and many different methods of
      calculation were used. The use of the multiplicative law of probability formula
      requires only knowledge of patient age and annual hemorrhage risk. Risk of
      hemorrhage = 1 - (risk of no hemorrhage) expected years of remaining life. The
      assumptions pertaining to this multiplicative formula include a constant yearly
      risk of hemorrhage and the independent behavior of all years of observation. We
      calculated the predictions of risk of hemorrhage across all age groups, as
      modified by published survival data. We think the use of this formula is
      justified by published natural history data across different ages and populations
      and that it is a simple and reasonable alternative to other methods of
      calculation.

PMID- 8559332
TI  - Correlation of the angioarchitectural features of cerebral arteriovenous
      malformations with clinical presentation of hemorrhage.
AB  - Superselective angiography is the most accurate technique in the analysis of
      brain arteriovenous malformation (AVM) angioarchitecture. Therefore, we reviewed
      the selective and superselective angiograms of 100 consecutive patients with
      intracerebral AVMs. Our purpose was to determine which parameters of
      angioarchitecture were significantly correlated with a clinical presentation of
      hemorrhage. The vascular characteristics evaluated on the angiograms were the
      size of the AVM, the location of the AVM, the type of nidus, the type of feeders,
      the characteristics of venous drainage, and the number and location of aneurysms.
      The parameters found to correlate with hemorrhage were deep venous drainage (P =
      0.01), feeding by perforators (P = 0.01), intranidal aneurysm(s) (P = 0.004),
      multiple aneurysms (P = 0.001), feeding by the vertebrobasilar system (P =
      0.002), and location in the basal ganglia (P = 0.04). Six parameters of AVM
      angioarchitecture were correlated with a clinical presentation of hemorrhage.
      Among these parameters, three (feeding by perforators, number of aneurysms, and
      presence of intranidal aneurysms) were well displayed by superselective
      angiogram.

PMID- 8559333
TI  - Short-term perioperative anticonvulsant prophylaxis for the surgical treatment of
      low-risk patients with intracranial aneurysms.
AB  - The long-term use of anticonvulsant medication to prevent postoperative seizures
      in patients with aneurysms has been accepted medical practice for many years. The
      low incidence of seizures in more recent aneurysm series makes it appropriate to
      re-evaluate the use of prophylactic anticonvulsants to prevent postoperative
      epilepsy, especially in patients at low risk of seizure disorders. On the basis
      of preoperative presentation, we categorized 387 of the 420 craniotomies for
      aneurysms over a 4-year period to be at low risk of seizure. Postoperative
      anticonvulsant medication in this group was restricted to an average of 3 days. A
      retrospective analysis of the incidence of early postoperative seizures and late
      postoperative seizure disorders was performed in the populations of patients with
      ruptured aneurysms and with unruptured aneurysms with an average follow-up of 2.4
      years. The overall seizure rate in the study group was 5.4%. Patients with
      ruptured aneurysms had an early postoperative seizure rate of 1.5% and a long
      term seizure disorder rate of 3.0%. Early and long-term seizure rates for
      unruptured aneurysms were 2.6 and 4.4%, respectively. No patients who had early
      seizures went on to develop epilepsy, and all seizure disorders were well
      controlled once anticonvulsants were begun. These data support the idea that
      anticonvulsant medication may be safely restricted to the immediate perioperative
      period for most patients with aneurysms.

PMID- 8559334
TI  - Complications of Swan-Ganz catheterization for hemodynamic monitoring in patients
      with subarachnoid hemorrhage.
AB  - Invasive hemodynamic monitoring has become standard in the management of
      aneurysmal subarachnoid hemorrhage. This study is a retrospective analysis of 630
      Swan-Ganz catheters placed in 184 patients with aneurysmal subarachnoid
      hemorrhage. Evaluation of complications demonstrated a 13% incidence of catheter
      related sepsis (81 of 630 catheters), a 2% incidence of congestive heart failure
      (13 of 630 catheters), a 1.3% incidence of subclavian vein thrombosis (8 of 630
      catheters), a 1% incidence of pneumothorax (6 of 630 catheters), and a 0%
      incidence of pulmonary artery rupture. In the management of patients with
      aneurysmal subarachnoid hemorrhage, invasive hemodynamic monitoring continues to
      be an important tool with acceptable complications.

PMID- 8559335
TI  - Current treatment of normal-pressure hydrocephalus: comparison of flow-regulated
      and differential-pressure shunt valves.
AB  - FROM THE RECORDS of approximately 1500 shunt operations performed between 1987
      and 1992, we identified 37 adults between ages 38 and 86 years (mean, 70 yr) with
      the normal-pressure hydrocephalus (NPH) syndrome who underwent surgery by a
      single surgeon. Since 1990, we have routinely used a flow-regulated shunt system
      (Orbis-Sigma valve [OSV]; Cordis Corporation, Miami, FL) in these patients. In
      this study, we compared the OSV system with conventional differential-pressure
      (DP) shunt systems uniformly used before 1990. This series (n = 37) consisted of
      62% men (n = 23) and 38% women (n = 14). We excluded all patients with
      hydrocephalus associated with central nervous system neoplasms, intracerebral
      hemorrhage, or trauma as well those with radiographically documented late-onset
      aqueductal stenosis. All patients presented with the NPH clinical syndrome,
      chiefly with magnetic gait. In addition, 75% of patients experienced cognitive
      loss and 59% experienced urinary incontinence. The mean duration of preoperative
      symptoms was 35 months (range, 7-120 mo). Eight patients (22%) had undergone
      previous shunting procedures before referral to our service. A total of 89 shunt
      operations were performed in the 37 patients. Using actuarial methods and
      controlling for a history of prior shunt surgery, we found no significant
      difference in the time to initial malfunction (shunt survival) between the OSV
      and the DP shunts. There were three subdural hematomas and one infection in the
      OSV group compared with no complications in the DP valve group (P = 0.11). Thirty
      six patients were available for follow-up, at a mean of 14 months after surgery.
      Nearly 90% of all patients experienced improvement in gait after shunting,
      regardless of the valve system that was used. There was one unrelated death.
      Realizing the limitations of a retrospective analysis and on the basis of the
      limited number of patients in this study, we conclude that using actuarial
      methods, we found no significant difference in shunt survival when comparing the
      OSV with the standard DP valve shunt systems with antisiphon devices in patients
      with NPH. Contrary to previous reports, the OSV is not free of overdrainage
      complications. Most patients (89%) with the NPH syndrome who primarily presented
      with gait disorder experienced significant improvement in gait after either OSV
      or DP shunting procedures when selected for surgery on the basis of the clinical
      syndrome and confirmatory radiographic data.

PMID- 8559336
TI  - Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in
      children: incidence and pathophysiology.
AB  - MUTISM AND A variety of other neurobehavioral symptoms have been reported
      anecdotally after the removal of posterior fossa mass lesions. To determine the
      incidence and clinical spectrum of this syndrome, a detailed review was performed
      of patients undergoing resection of infratentorial tumors at our institution
      during the last 9 years; 12 of 142 patients (8.5%) manifested this syndrome, the
      largest series of such patients reported to date. Each child had a lesion that
      involved the vermis; seven had medulloblastomas, three had astrocytomas, and two
      had ependymomas. The incidence among children with vermian neoplasms was 13%. Ten
      children underwent division of the inferior vermis during tumor resection, and
      three had a superior vermian incision; one child underwent both superior and
      inferior vermian incisions. In 10 children, mutism developed in a delayed fashion
      postoperatively. The speech disturbance was associated with poor oral intake in 9
      children, urinary retention in 5, long-tract signs in 6, and bizarre personality
      changes, emotional lability, and/or decreased initiation of voluntary movements
      in all 12. Neuropsychiatric testing, performed in seven children, confirmed
      impairments not only in speech but also in initiation of other motor activities.
      Ten children regained normal speech, bladder control, and neurological
      functioning, other than ataxia and mild dysarthria, within 1 to 16 weeks; two
      children had significant residual deficits. Characteristically, affect and oral
      intake returned to their preoperative baseline before the speech difficulties
      began to resolve. A detailed radiological review of these cases in parallel with
      24 cases of vermian tumors without mutism identified only one factor that was
      significantly associated with the mutism syndrome, bilateral edema within the
      brachium pontis (P < 0.01). Neither the size of the tumor nor the length of
      vermian incision was associated with the development of mutism. The clinical
      features of this syndrome in the context of these imaging findings suggest that
      the mutism syndrome results from transient impairment of the afferent and/or
      efferent pathways of the dendate nuclei that are involved in initiating complex
      volitional movements. The clinical courses of our patients are presented and
      compared with those of similar cases in the literature in an attempt to evaluate
      the validity of this hypothesis.

PMID- 8559337
TI  - Transient cerebellar mutism after posterior fossa surgery in children.
AB  - Cerebellar mutism has been reported after surgery for posterior fossa tumors in
      children and, rarely, in adults. The pathogenesis of this syndrome remains
      unclear, and controversy exists regarding whether it is a purely psychogenic
      disorder or an organic syndrome. The anatomical substrate for the mutism also
      remains unknown. We encountered five cases of postoperative transient cerebellar
      mutism in a consecutive series of 63 children with posterior fossa tumors. These
      cases were analyzed and compared with the patients without mutism to find
      predictive factors for the occurrence of mutism, with the hope of elucidating
      further the pathophysiological mechanism. The most significant finding was the
      presence in all cases of a period of cerebellar dysarthria after resolution of
      the muteness. We, therefore, believe that cerebellar mutism is an extreme form of
      dysarthria, rather than a real cognitive deficit or a psychological disturbance.

PMID- 8559338
TI  - Evolving brain lesions in the first 12 hours after head injury: analysis of 37
      comatose patients.
AB  - From January 1, 1990, to April 30, 1994, 412 patients were admitted to our
      intensive care unit in coma after head injuries. Our study group consisted of 37
      patients who were retrospectively identified as harboring lesions or developing
      new lesions within a 12-hour period from the time of admission. We defined the
      evolution of a lesion as an increase or decrease in the size of an already
      present hematoma or as the appearance of a totally new lesion. There were 25 male
      and 12 female patients (mean age, 34.9 yr), and the cause of trauma was road
      traffic accidents in 32 patients. Nine patients presented with shock, and six had
      evidence of abnormal coagulation at admission. Patients were divided into two
      different groups. In Group 1, 15 patients harbored lesions that evolved toward
      reabsorption. In Group 2, 22 patients harbored hematomas that evolved toward
      lesions requiring surgical removal. Fifteen of these patients had initial
      diagnoses of diffuse injury that evolved in this manner, whereas the remaining
      seven patients had already been operated upon and had developed second,
      noncontiguous, surgical lesions. Patients with lesions that required surgical
      evacuation had their computed tomographic (CT) scans obtained earlier and had a
      higher incidence of clinical deterioration. There was a significant difference in
      the evolution of the different lesions (P < 0.001), with subdural hematomas being
      more prone to reabsorption and intracerebral and extradural hematomas being more
      likely to increase in size or to appear as new lesions. Second CT scans were
      obtained because of clinical deterioration in 10 patients and because of increase
      in intracranial pressure in 5 patients. Scheduled CT scans were obtained in 13
      patients, whereas in the remaining 9 patients, the diagnosis emerged from a
      combination of scheduled CT scans and intracranial pressure monitoring. There was
      a trend toward a poorer result among the patients with clinical deterioration,
      which, however, was not significant. A significant proportion of post-traumatic
      patients, particularly those who are unconscious, harbor early evolving
      intracranial lesions. When the first CT scan is performed within 3 hours after
      injury, a CT scan should be repeated within 12 hours.

PMID- 8559339
TI  - Retropleural approach to the thoracic and thoracolumbar spine.
AB  - Retropleural thoracotomy was used in 15 patients for the management of ventral
      thoracic and thoracolumbar spine abnormalities. This approach provides the
      shortest direct route to the anterior thoracic spine and avoids pleural cavity
      entry. A detailed description of retropleural thoracotomy and the clinical
      experiences of 15 patients treated with it are presented.

PMID- 8559340
TI  - Staged removal of acoustic tumors: techniques and lessons learned from a series
      of 83 patients.
AB  - The removal of large acoustic tumors is associated with increased mortality and
      cranial nerve injury. One method for treating these difficult lesions is staged
      resection. Between 1972 and 1992, more than 600 acoustic tumors were resected at
      our institution. Of these, 83 were removed in stages. This represents the largest
      series of staged acoustic tumor resections reported to date. A review of
      available films and patient records was performed for all acoustic tumors
      resected in stages between 1972 and early 1993 to analyze demographic
      information, tumor size, operative technique, outcome, and complications. The
      information was collected on standardized data sheets and entered into a computer
      database. Virtually all tumors were large, with the average size being 4 cm in
      greatest diameter. The average patient age was 41 years, and there was a slight
      preponderance of female patients. Ten patients had neurofibromatosis Type 2. The
      suboccipital approach was used in most patients. Anatomic preservation of the
      VIIth cranial nerve was achieved in > 72% of patients, with an average House
      Brackmann score of Grade 3 at the longest follow-up (mean, 43 mo). Facial
      reanimation was performed in 19 of 23 patients with transected VIIth cranial
      nerves. Complications included cerebrospinal fluid fistulas in 11 patients, with
      8 of 11 fistulas resolving after lumbar drainage. Six patients had meningitis
      (bacterial in three and aseptic in three). Two patients developed wound
      infections, and 10 patients developed exposure keratitis. There were two
      documented recurrences. There were no operative deaths. In most series, the
      incidence of cranial nerve deficits as well as morbidity and mortality is
      directly related to tumor size. Our operative strategy involved debulking the
      lateral aspect of large tumors during Stage I. Second stage removal is performed
      after the remaining tumor is shown to decompress out of the pons on computed
      tomographic or magnetic resonance images. During the second procedure, the
      residual tumor is less vascular and no longer densely adherent to the brain stem.
      Although staged removal is not without risk, there seems to be no apparent
      increase in morbidity when these results are compared with the results of series
      from the literature. Although there remain no absolute indications for staged
      resection of acoustic tumors, we think that it may represent the safest option
      for these difficult lesions.

PMID- 8559341
TI  - Brain stem mapping: neurophysiological localization of motor nuclei on the floor
      of the fourth ventricle.
AB  - We have improved upon a brain stem mapping technique that can be used to locate
      cranial motor nuclei on the floor of the fourth ventricle. This technique helped
      to intraoperatively locate the facial colliculus and the motor nuclei of cranial
      nerves IX/X and XII in 14 patients undergoing removal of brain stem tumors. The
      motor nuclei of these cranial nerves are usually located relative to specific
      anatomic landmarks on the ventricular floor. These landmarks were not evident in
      most patients studied because of the distorting effects of the tumor. Different
      points of the floor of the fourth ventricle were electrically stimulated while
      electromyographic responses were recorded with electrodes inserted in the
      orbicularis oculi and orbicularis oris muscles, the lateral posterior pharyngeal
      wall, and the intrinsic muscles of tongue. Mapping was performed before and after
      tumor resection. The technique was found to be useful for locating cranial motor
      nuclei before tumor resection. It enabled surgeons to avoid damaging the nuclei
      when entering the brain stem. This technique, however, has certain limitations.
      Because this is a mapping technique, not a monitoring technique, continuous
      monitoring during tumor resection was unavailable. Also, the presence of a muscle
      response after tumor resection did not always indicate preservation of immediate
      postoperative function (7 days after surgery) because damage to the corticobulbar
      tract and/or the underlying neural circuitry was not detectable by mapping.
      Further research is needed to determine the point of stimulation in the
      functional motor circuitry and the relationship between intraoperative recordings
      and postoperative function in the long term.

PMID- 8559342
TI  - Sequelae of carpal tunnel surgery: rationale for the design of a surgical
      approach.
AB  - The sequelae of carpal tunnel surgery were reviewed and were presumed to be
      associated with the linear vertical section of the transverse carpal ligament
      because this was the common element in the reported series. The authors adopted a
      modified approach, substituting a parabolic incision that left a protective flap
      of the ligament to cover the structures within the tunnel in the area of maximum
      convexity of the wrist. The results from a recent series of 100 cases were
      contrasted with a control series of 770 previous cases. Untoward postoperative
      sequelae were significantly reduced through this modified approach. The improved
      results, the authors conclude, were attributable to a reduction of pressure
      within the carpal tunnel, while avoiding the wide gaping of the tunnel space that
      is associated with vertical incisions, which may allow an anterior displacement
      of the median nerve and flexor tendons between the cut ends of the transverse
      carpal ligament and sometimes result in a continuous scar through the skin.

PMID- 8559343
TI  - Inhibition of in vitro meningioma proliferation after growth factor stimulation
      by calcium channel antagonists: Part II--Additional growth factors, growth factor
      receptor immunohistochemistry, and intracellular calcium measurements.
AB  - We have previously reported that calcium channel antagonists can block both the
      growth of meningiomas in culture and the potent growth stimulation of meningioma
      cells by epidermal growth factor (EGF) and platelet-derived growth factor (PDGF).
      This study further defines the nature of this growth inhibition. Primary
      meningioma cultures were established, and cells were characterized. Fibroblast
      growth factor or insulin-like growth factor-I growth stimulation in the presence
      of calcium channel antagonists was examined. In addition, the effects of ethylene
      glycol-bis-(aminoethylether) N,N,N',N"-tetraacetic acid and Bay K 8644, a calcium
      channel agonist, on the growth factors were analyzed. Growth factor receptor
      immunohistochemistry was performed on the original tumors and the in vitro
      meningioma cells. Twelve of 17 (71%) meningiomas in this study were positive for
      the EGF receptor, and 14 of 17 (82%) were positive for the PDGF receptor. Five of
      six (83%) of the culture cells were positive for the EGF receptor, and four of
      five (80%) were positive for the PDGF receptor. Intracellular calcium changes
      were quantified using the intracellular calcium-chelating, fluorescent dye, Fura
      2. The growth stimulation of fibroblast growth factor and insulin-like growth
      factor-I on meningioma cells in culture was decreased in a dose-dependent manner
      by calcium channel antagonists. The growth stimulation of fibroblast growth
      factor and insulin-like growth factor-I was not affected by a reduction of
      extracellular calcium, whereas the growth stimulation of EGF and PDGF was.
      Interestingly, intracellular calcium was not increased after exposure to growth
      factors but was increased after serum stimulation. This increase could be blocked
      by preincubation with verapamil. Calcium channel antagonists can inhibit
      proliferation of meningioma cells in culture after stimulation with a number of
      growth factors. These drugs might disrupt intracellular calcium homeostasis or
      interfere with key elements of the growth factor signal transduction pathways.
      These mechanisms as well as the potential clinical relevance of these findings
      are discussed.

PMID- 8559344
TI  - Alterations in striatal dopamine release and reuptake under conditions of mild,
      moderate, and severe cerebral ischemia.
AB  - Cerebral ischemia can result in varying degrees of tissue damage. Conditions of
      severe ischemia can produce extensive areas of irreversible injury, whereas in
      conditions of moderate ischemia, tissue damage may be reversible, as in the
      region of the ischemic penumbra. The reversibility of tissue damage in the
      penumbral region is of clinical interest, because the characterization of
      conditions underlying this reversible state may provide information needed for
      the development of new therapeutic approaches for treatment. Our previous studies
      demonstrated neurochemical alterations in the levels of dopamine (DA) within the
      striatum after cerebral ischemia. In the present study, we postulate that these
      changes may be caused, in part, by alterations in transmitter release and
      reuptake. To test this hypothesis, forebrain ischemia was induced in Sprague
      Dawley rats (Harlan, Indianapolis, IN) by means of bilateral common carotid
      artery occlusion and hemorrhagic hypotension. Cerebral blood flow (CBF) in the
      striatum was measured by the method of hydrogen clearance, and the extracellular
      DA ([DA]e) levels were measured by in vivo microdialysis. Varied reductions of
      CBF were induced and maintained for 5 hours. Three subgroups were established
      retrospectively according to the degree of CBF reduction: 67.7, 35.6, and 13.2%
      of normal CBF in the mild, moderate, and severe ischemic groups, respectively.
      The induction of ischemia resulted in 1.9-, 9.3-, and 122.3-fold increases in
      [DA]e above baseline in the mild, moderate, and severe ischemia groups,
      respectively. At 3 hours after the induction of ischemia, high potassium (100
      mmol/L) or Nomifensin (Sigma, St. Louis, MO) (10 mmol/L), a DA uptake blocker,
      was administrated via a microdialysis probe to stimulate DA release while
      reductions in CBF were maintained continuously. Thirteen rats were used in the
      study of the release of DA by potassium or Nomifensin in nonischemic conditions.
      The administration of high potassium or Nomifensin stimulated DA release in
      conditions of mild and moderate ischemia. The increase in DA release by potassium
      stimulation was higher in rats with mild ischemia (106.6-fold) than that in
      normal rats (22.3-fold). This suggests a hyperexcitability of DA terminals under
      mild ischemia, as compared with nonischemic conditions. On the other hand,
      Nomifensin increased [DA]e levels more in moderately ischemic brains than in
      control brains, suggesting that DA uptake is up-regulated in the former case. The
      increased release of DA by potassium and Nomifensin was sustained after
      stimulation in conditions of mild and moderate ischemia. The high level of [DA]e
      with severe ischemia after ischemic induction was sustained throughout the period
      of study and was not stimulated by potassium or Nomifensin. We conclude that
      under conditions of mild and moderate ischemia, DA terminals become highly
      excitable and reuptake mechanisms are compromised. These changes of DA metabolism
      during mild and moderate ischemia may explain the sustainability of neurons in
      the "penumbra" condition of cerebral ischemia and the transformation of the
      ischemic penumbra to a necrotic core.

PMID- 8559345
TI  - Expression of tissue plasminogen activator in cerebral capillaries: possible
      fibrinolytic function of the blood-brain barrier.
AB  - Previous work has shown that tissue plasminogen activator (tPA) is a key enzyme
      in the control of fibrinolysis within the vascular system. The sources of brain
      tPA and the mechanisms by which tPA secretion and production occur within
      cerebral microcirculation are not well established. In this study, expression of
      tPA was investigated in cerebral capillaries and capillary-depleted brain
      isolated from cortices of 4- to 5-week-old rats and guinea pigs. In both species,
      a single tPA band of M(r) 67,000 was detected in cerebral capillaries by Western
      blot analysis. The tPA signal was absent from capillary-depleted brain. These
      results were corroborated at the messenger ribonucleic acid level. Reverse
      transcription-polymerase chain reaction analysis revealed the presence of tPA
      complementary deoxyribonucleic acid in samples derived from cerebral microvessels
      and demonstrated very low or undetectable tPA expression in capillary-depleted
      brain. Immunohistochemical analysis confirmed tPA localization in endothelial
      cells of brain capillaries. We conclude that microvascular endothelium, i.e., the
      blood-brain barrier, may have a role in promoting plasmin-dependent fibrinolysis
      in brain microcirculation. Delineation of the molecular mechanisms of blood-brain
      barrier-mediated fibrinolysis will likely contribute to future stroke prevention
      efforts.

PMID- 8559346
TI  - Papaverine-sensitive vasospasm and arterial contractility and compliance after
      subarachnoid hemorrhage in dogs.
AB  - This study examined the relationship between papaverine-sensitive and 
      insensitive components of vasospasm, arterial contractility and compliance, and
      time after subarachnoid hemorrhage (SAH) in dogs. Eighteen dogs underwent
      angiography and then two intracisternal injections of blood. Angiography was
      repeated 4 (n = 5), 7 (n = 4), 10 (n = 4), or 14 (n = 5) days later. Papaverine,
      100 to 200 mg, was infused into the basilar artery, and angiography was repeated.
      Four additional dogs had cerebral angiography only and served as controls. The
      basilar arteries were removed and studied pharmacologically. Significant
      vasospasm of the basilar artery was observed each time after SAH. Papaverine
      significantly reversed vasospasm at 4 and 7 days (88 +/- 6% and 63 +/- 11% of
      vasospasm reversed; analysis of variance, P < 0.05). The papaverine-insensitive
      component of vasospasm increased significantly with increasing time after SAH and
      with increasing severity of vasospasm. Arterial contractility and compliance
      decreased significantly with increasing time after SAH and were significantly
      related to the degree of papaverine-insensitive vasospasm but not to the severity
      of vasospasm. In conclusion, the majority of vasospasm early after SAH in dogs
      was caused by reversible vasoconstriction. The ability of papaverine to reverse
      vasospasm depended on the time after SAH and on the severity of vasospasm, a
      finding that may be important to the use of papaverine in humans. The
      pathological and biochemical basis for the association between papaverine
      insensitive vasospasm and reduced arterial wall contractility and compliance
      remains to be determined.

PMID- 8559347
TI  - The effects of propofol on rat transcranial magnetic motor evoked potentials.
AB  - INTRAOPERATIVE MONITORING OF motor evoked potentials (MEPs) may become a valuable
      test of spinal cord function during surgery. Unfortunately, MEP responses are
      affected by most common anesthetics. We studied the effect of intravenous
      propofol on transcranial magnetic MEPs (tcMMEPs) in the rat. Baseline tcMMEPs
      were recorded before administration of the drug. Each rat then received three
      induction doses of propofol, 10, 5, and 5 mg/kg (totaling 10, 15, and 20 mg/kg)
      and three successive 20-minute infusion doses at rates of 10, 20, and 40 mg/kg/h,
      respectively. An MEP intensity series was performed after each induction dose,
      during each infusion, and during a 20-minute recovery period. tcMMEPs recorded
      during the induction period demonstrated a significant, dose-dependent increase
      in onset latency and a marked decrease in amplitude. Infusion tcMMEPs displayed
      increased onset latencies but demonstrated a significant change in amplitudes
      only after the largest infusion dose. The MEPs approached baseline levels after
      discontinuation of the propofol. This study demonstrates that tcMMEPs can be
      successfully recorded from the rat during propofol anesthesia.

PMID- 8559348
TI  - Peri-insular hemispherotomy: surgical principles and anatomy.
AB  - THE NATURE OF functional hemispherectomy continues to be misunderstood despite
      its 20-year history. Recently, we introduced the concept of peri-insular
      hemispherotomy, a functional hemispherectomy with minimal brain removal (9, 21).
      To avoid additional confusion, a detailed neuroanatomic account of this
      operation, which has been performed in 11 patients, is presented. The name of the
      operative variant presented derives from the central importance of the exposure
      of the insula as the first surgical landmark. Incising along the circular sulcus
      that surrounds the insula not only allows access to the dilated ventricular
      system but also disrupts the entire internal capsule. A parasagittal callosotomy
      is performed from within the lateral ventricle by incising the medial ventricular
      roof. Projections through the anterior commissure are disrupted at the time of
      radical amygdalar resection. The posterior hippocampus need not be radically
      removed, because its posterior transsection disconnects it. Overall, peri-insular
      hemispherotomy can be viewed as a radical hemispheric tractotomy, resulting in a
      completely disconnected hemisphere. Advantages include shorter operative times, a
      less stormy postoperative course, and better anatomic preservation of the
      operated hemisphere, thus presumably reducing long-term complications.

PMID- 8559349
TI  - Extent of medial temporal resection on outcome from anterior temporal lobectomy:
      a randomized prospective study.
AB  - WE REPORT A prospective, randomized, blinded clinical trial comparing seizure and
      neuropsychological outcomes from anterior temporal lobectomies between two groups
      of patients. One group (n = 34) underwent hippocampal resection posteriorly to
      the anterior edge of the cerebral peduncle (partial hippocampectomy). In the
      other group (n = 36), the hippocampus was removed further to the level of the
      superior colliculus (total hippocampectomy). The amount of lateral cortical
      resection was the same between groups. Patients were and neuropsychological
      morbidity. At 1 year postoperatively, the total hippocampectomy group had a
      statistically superior seizure outcome compared with the partial hippocampectomy
      group (69 versus 38% seizure-free), and examination of time to first seizure
      (survival analysis) revealed significantly superior outcomes associated with
      total hippocampectomy. There was no increased neuropsychological morbidity
      associated with the more extensive hippocampal resection.

PMID- 8559350
TI  - Retained language in dysgenic cortex: case report.
AB  - Since the advent of magnetic resonance imaging, there has been renewed interest
      in disorders of cortical migration in the cause of focal epilepsy. The function
      of dysplastic cortex is poorly understood. We report a 46-year-old woman in whom
      this was assessed by intraoperative stimulation. This left-handed patient had a
      30-year history of complex partial seizures with secondary generalization.
      Prolonged electroencephalographic recordings documented an epileptic focus in the
      right lateral and inferomesiotemporal lobe. Computed tomographic scanning and
      angiography suggested a right posterotemporal hamartoma. Amytal testing showed
      major speech representation in the right hemisphere. At craniotomy, an ivory
      colored, posterotemporal lesion originating 5 cm from the temporal tip and 4 cm
      in diameter occupied the posterotemporal region. Electrical stimulation of this
      lesion produced speech interference. A histological examination of the resected
      anterotemporal lobe, amygdala, and hippocampus and biopsy specimens of the lesion
      showed extensive multifocal cortical microdysgenesis and gliovascular and
      cortical hamartoma. This case shows that grossly dysplastic cortex can remain
      functional. Cortical mapping under local anesthesia should be performed before
      resection of dysplastic lesions in putatively functional areas in patients with
      intractable epilepsy.

PMID- 8559352
TI  - XXIst Congress and 5th Advanced Course of the European Society of Neuroradiology.
      Budapest, Hungary, 20-23 September 1995. Abstracts.

PMID- 8559351
TI  - Rapidly growing histologically benign meningiomas: cell kinetic and
      deoxyribonucleic acid ploidy features: report of three cases.
AB  - We present three cases of histologically benign meningiomas with a rapid and
      known time course to the development of symptoms. Tumor doubling time calculated
      from sequential computed tomographic scans and computer-assisted image analysis
      of proliferating cell nuclear antigen reactivity suggested rapid growth. Feulgen
      staining indicated deoxyribonucleic acid aneuploidy. Tests for progesterone and
      estrogen receptor immunoreactivity were negative. These cases are noteworthy for
      their uncharacteristically rapid growth in the absence of histological evidence
      of atypia.

PMID- 8559353
TI  - Pilot trial of immunoglobulin versus plasma exchange in patients with Guillain
      Barre syndrome.
AB  - We compared intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) in the
      treatment of 50 patients with Guillain-Barre syndrome (GBS). Standard outcome
      measures did not differ for the two groups. Sixty-one percent of the PLEX-treated
      group and 69% of the IVIG-treated group improved by one disability grade at 1
      month. The complication rate was higher in the PLEX-treated group. We conclude
      that the efficacy of IVIG in the treatment of GBS is comparable with that of PLEX
      and that it can be used safely, although we had a small number of patients. We
      did not observe a higher relapse rate with IVIG. The usefulness of combination
      therapy is unknown at this time.

PMID- 8559354
TI  - Peripheral neurotoxicity induced by docetaxel.
AB  - Docetaxel, a new semisynthetic taxoid used as an antineoplastic agent, induced a
      predominantly sensory neuropathy in 20 of 41 patients. We assessed neurotoxicity
      in all patients participating in four phase II trials conducted in our
      institution. The neuropathy was evaluated by a clinical sum-score for symptoms
      and signs and by measurement of the Vibration Perception Threshold (VPT). The
      severity of neuropathy was graded according to the National Cancer Institute's
      Common Toxicity Criteria. Neuropathic symptoms were mild in most patients.
      However, at cumulative doses above 600 mg/m2, 3 of 15 patients developed a
      moderate and 1 of 15 patients a severe neuropathy. There was a significant
      correlation between the cumulative dose of docetaxel and the post-treatment sum
      score (p = 0.002). We found no correlation between post-treatment VPT and
      clinical sum-score or between post-treatment VPT and the cumulative dose of
      docetaxel. We conclude that docetaxel produced a mild and predominantly sensory
      neuropathy in a high proportion of treated patients. This neurotoxicity appeared
      to be dose dependent and may be severe and disabling at higher dose levels.
      Determination of the VPT is not a reliable method to monitor docetaxel-induced
      neuropathy.

PMID- 8559355
TI  - Peripheral neuropathy secondary to docetaxel (Taxotere)
AB  - Docetaxel (Taxotere), a semisynthetic analogue of the antitumor agent paclitaxel,
      inhibits tubulin depolymerization. Paclitaxel produces a peripheral neuropathy.
      This study delineates clinically and electrophysiologically the characteristics
      of a peripheral neuropathy due to docetaxel. In 186 patients receiving docetaxel
      in phase I and phase II protocols, we performed serial neurologic exams. As
      patients became symptomatic, quantitative sensory testing and nerve conduction
      studies were done. Twenty-one patients developed mild to moderate sensory
      neuropathy on taxotere at a wide range of cumulative doses (50 to 750 mg/m2) and
      dose levels (10 to 115 mg/m2). Ten of these patients also developed weakness of
      varying degree in proximal and distal extremities. Nine of the 21 patients had
      received neurotoxic chemotherapy before; 16 were treated with docetaxel at a dose
      level of 100 to 115 mg/m2. In summary, docetaxel produced a sensorimotor
      peripheral neuropathy in 11% of our patient population.

PMID- 8559356
TI  - Peripheral nerve abnormalities in adrenomyeloneuropathy: a clinical and
      electrodiagnostic study.
AB  - Adrenomyeloneuropathy (AMN) is one of the most frequent phenotypes of X-linked
      adrenoleukodystrophy. Whether the polyneuropathy in AMN results from primary
      demyelination or axonal degeneration is uncertain. We examined 23 patients (18
      men with AMN and five female carrier with AMN symptomatology), performed
      electroneurography and EMG, and compared our results with standardized
      electrodiagnostic criteria for primary demyelination. Both clinically and
      electrodiagnostically, the lower extremities were most frequently and most
      severely affected. A longer duration of symptoms was related to more severe
      pyramidal dysfunction (p < 0.004) and spasticity (p < 0.04), and to a more severe
      impairment of vibration sense (p < 0.05). There were on correlations between the
      different electrophysiologic studies and the duration of neurologic symptoms.
      Only two AMN patients (9%) fulfilled the electrodiagnostic criteria for primary
      demyelination. However, both had abnormally low compound muscle action
      potentials, which may have been a reflection of primary axonal degeneration. Six
      other patients (26%) partially fulfilled the criteria for primary demyelination,
      of whom five also manifested low compound muscle action potentials. In 15
      patients (65%), we found polyneuropathy with predominantly axonal, sensorimotor
      features. We conclude that the neuropathy in AMN patients is due to primary
      axonal degeneration.

PMID- 8559357
TI  - Friedreich's ataxia with retained tendon reflexes: molecular genetics, clinical
      neurophysiology, and magnetic resonance imaging.
AB  - Lower limb areflexia is generally regarded as an essential criterion for the
      diagnosis of Friedreich's ataxia (FRDA). We describe a family with a recessive
      form of early-onset ataxia in which one member had a phenotype typical of FRDA
      whereas another, with retained tendon reflexes in the lower limbs, did not have
      electrophysiologic evidence of the usual severe afferent axonal neuropathy of
      FRDA. In contrast, somatosensory evoked potentials, eye-movement recordings, and
      MRI of the head and cervical cord provided results highly suggestive of FRDA in
      both patients. We performed genetic linkage analysis in this family, using
      markers tightly linked to the FRDA locus on chromosome 9. Inheritance of
      identical paternal and maternal genotypes by the affected members, but not by
      their unaffected siblings, provided supporting evidence that this disorder may
      result from mutation within the FRDA gene or is tightly linked to the
      investigated loci on chromosome 9.

PMID- 8559358
TI  - Management of patients receiving interferon beta-1b for multiple sclerosis:
      report of a consensus conference.
AB  - Results of a double-blind, placebo-controlled study in ambulatory patients with
      relapsing-remitting MS showed that interferon beta-1b reduced the rate of
      exacerbations by one-third compared with placebo and limited new disease activity
      in the brain as evidenced by MRI. Interferon beta-1b, administered subcutaneously
      at a dosage of 0.25 mg (8 million IU) every other day is indicated for the
      treatment of ambulatory patients with relapsing-remitting MS. Interferon beta-1b
      may help a wider range of patients, but it should be prescribed only for patients
      with a diagnosis of clinically definite or laboratory-supported definite MS. The
      decision to treat a patient with interferon beta-1b should be individualized;
      that is, based on each patient's clinical presentation and course of MS. The most
      common adverse effects include (1) injection-site reactions and (2) flu-like
      symptoms, which are generally manageable and usually abate after the first few
      months of treatment. Spasticity may increase. Patients with severe depression or
      suicidal ideation should be monitored carefully, and symptomatic treatment should
      be pursued. Interferon beta-1b is contraindicated in pregnant and nursing women.
      Interferon beta-1b is effective in reducing the progression of total disease
      burden as seen on MRI in patients with MS. Its use is relatively straightforward
      and generally does not require alteration in the symptomatic treatment of MS.
      Patient education and support remain the mainstays of maintaining compliance
      through the early phases of therapy.

PMID- 8559359
TI  - Subjective memory complaints may announce dementia.
AB  - Whether subjective memory complaints in the absence of objective memory decline
      can predict future dementia has been investigated only in highly selected
      clinical and volunteer cohorts. Our study examines this question in a subsample
      of AMSTEL (Amsterdam Study of the Elderly), a longitudinal population study on
      cognitive decline and dementia. Subjects (aged 65 to 84 years; n = 357) without
      dementia or other psychiatric disorders at baseline were followed for 3 years.
      After this interval, 16 of 203 re-examined patients developed a dementia.
      Logistic regression analyses indicated that memory complaints at baseline
      contributed a small but significant amount of diagnostic information. However,
      the most powerful predictor of future dementia was deficient memory performance.
      We conclude that subjective memory complaints may predict dementia within 3
      years, particularly when there are objective signs of memory deterioration.

PMID- 8559360
TI  - Increased risk of familial late-onset Alzheimer's disease in women.
AB  - The role of gender in the pathogenesis of Alzheimer's disease (AD) is an
      important issue that remains controversial. We compared men and women in late
      onset familial AD kindreds for the risk of developing AD by studying 26 well
      characterized familial AD kindreds from the Oregon Alzheimer Disease Center and,
      for confirmation, an additional 32 kindreds from the National Cell Repository
      (NCR) at the Indiana University Alzheimer Disease Center. Comparing women to men,
      the age-adjusted odds ratio estimates were 3.2 (p = 0.0002) for the Oregon data
      and 2.3 (p = 0.004) for the NCR data. These results suggest that gender is an
      independent risk factor for familial late-onset AD and may play a role in the
      pathogenesis of this disease.

PMID- 8559361
TI  - The spectrum of behavioral changes in Alzheimer's disease.
AB  - We investigated the range of behavioral abnormalities in patients with
      Alzheimer's disease (AD) compared with normal age-matched control subjects. The
      range of behavioral disturbances manifested and the relationship between specific
      abnormalities with the level of cognitive impairment have not been established.
      Fifty consecutive outpatients with mild (n = 17), moderate (n = 20), and severe
      (n = 13) AD and 40 age-matched normal controls were evaluated for behavioral
      abnormalities occurring in the month preceding the interview. The caregivers of
      the patients and the spouses of the control subjects were interviewed with the
      Neuropsychiatric Inventory (NPI). The frequency and severity of the following 10
      behaviors were assessed: delusions, hallucinations, agitation, dysphoria,
      anxiety, euphoria, apathy, disinhibition, irritability, and aberrant motor
      behavior. Correlations among these 10 behaviors and their relationship with
      cognitive impairment were also investigated. Eighty-eight percent of AD patients
      had measurable behavioral changes. All 10 behaviors were significantly increased
      in the AD patients compared with normal subjects. The most common behavior was
      apathy, which was exhibited by 72% of patients, followed by agitation (60%),
      anxiety (48%), irritability (42%), dysphoria and aberrant motor behavior (both
      38%), disinhibition (36%), delusions (22%), and hallucinations (10%). Agitation,
      dysphoria, apathy, and aberrant motor behavior were significantly correlated wit
      cognitive impairment.

PMID- 8559362
TI  - Clinical and neuropsychological differences between patients with earlier and
      later onset of Alzheimer's disease: A CERAD analysis, Part XII.
AB  - To determine whether the age of the onset of Alzheimer's disease (AD) is related
      to the expression and rate of decline of this disorder, we examined the clinical
      and neuropsychological performance of 421 patients entered into the Consortium to
      Establish a Registry for Alzheimer's Disease and followed annually for up to 4
      years. Statistical analyses were based on multivariable logistic regression
      analysis for dichotomous clinical measures and multivariable linear regression
      analysis for psychometric measures. All analyses examined the effect of age after
      controlling for gender, education, and stage of dementia. Clinical information
      obtained on entry into the study indicated that younger patients performed more
      poorly on measures of language and concentration, and older patients performed
      more poorly on measures of memory and orientation. On neuropsychological measures
      at entry, younger patients, performed more poorly on praxis and had significantly
      higher scores of confrontation naming. Younger age predicted a significantly
      faster rate of progression for all neuropsychological measures. These findings
      support the concept of age-related clinical subtypes of AD.

PMID- 8559363
TI  - The consortium to establish a registry for Alzheimer's Disease (CERAD). Part
      XIII. Obtaining autopsy in Alzheimer's disease.
AB  - Although autopsy rates in the United States have been decreasing steadily, the
      necessity for brain autopsy to confirm Alzheimer's disease (AD) remains. Of 308
      consecutively deceased AD patients at 24 CERAD (Consortium to Establish a
      Registry for Alzheimer's Disease) sites, 167 (54%) were autopsied; 141 (46%) were
      not. The autopsied and nonautopsied groups were comparable in gender (men, 57.5%
      versus 49.7%), marital status (married, 69.3% versus 67.1%), age at entry (73
      versus 74 years), age at death (76 versus 77 years), and stage of disease at
      entry (mild, 46% versus 43%). However, the autopsied patients were significantly
      more likely to be white (94.5% versus 82.1%), to be better educated (13.1 versus
      11.3 years), to have been in the study longer (mean, 3.3 versus 2.6 years), and
      to have had longer total duration of AD (8.1 versus 6.7 years). Of the 24 CERAD
      sites, 13 stressed the importance of autopsy by dedicating a staff member to seek
      autopsy and by providing free autopsy and transportation; 11 did not. Logistic
      regression analysis showed that white race (odds ratio [OR] = 2.74; 95%
      confidence interval [CI] = 1.10-6.83), increased education (OR = 1.12; 95% CI =
      1.04-1.21), and emphasis on autopsy (OR = 4.69; 95% CI = 2.67-8.25) were the only
      significant factors. Although race and education were important, autopsy was more
      likely to be obtained when sites dedicated resources to this endeavor.

PMID- 8559364
TI  - Apolipoprotein E genotype and Alzheimer's disease in Hong Kong elderly Chinese.
AB  - We studied the apolipoprotein E (apoE) allele frequencies in 65 Chinese patients
      with late-onset Alzheimer's disease (AD) and 82 age- and sex-matched controls.
      The apoE epsilon 4 allele frequency was significantly higher in the AD group than
      in the control group (0.169 versus, p < 0.01). There were five homozygotes for
      epsilon 4 in the AD group but none among the controls. The odds ratio for AD was
      1.6 for epsilon 4 heterozygotes. The age at onset was lower in the presence of
      the epsilon 4 allele and higher with the epsilon 2 allele, although neither of
      these differences reached statistical significance. The association between apoE
      alleles and AD previously reported in Caucasian populations was also present in
      this reports of lower prevalence of AD compared with the prevalence of multi
      infarct dementia.

PMID- 8559365
TI  - A prospective study of the clinical utility of ApoE genotype in the prediction of
      outcome in patients with memory impairment.
AB  - Given the relationship between the presence of ApoE epsilon 4 and Alzheimer's
      disease (AD), were studied whether knowledge of epsilon 4 status would predict
      which memory-impaired patients would develop AD over time. One hundred seven
      patients who presented with memory impairment but not dementia were referred to
      the study by their family physicians. These patients were followed prospectively
      over a 2-year period. Twenty-nine patients developed AD, while 78 did not develop
      dementia. We found that ApoE genotype was a reliable prognostic indicator of who
      developed AD in this group only when memory test performance was included in the
      predictive model. These findings indicate that limitations of ApoE genotyping in
      isolation as a prognostic indicator of AD. Because this study included
      prospectively selected patients who were followed longitudinally, our findings
      are likely to have more relevance in the clinical setting than those obtained
      from currently available retrospective studies.

PMID- 8559366
TI  - Dementia after ischemic stroke: a population-based study in Rochester, Minnesota
      (1960-1984)
AB  - We used the medical records linkage system for the population of Rochester,
      Minnesota, to identify persons in the community who had their first cerebral
      infarct without previous dementia. In this cohort (n = 971), the incidence of
      dementia in the first year was nine times greater than expected, but if we did
      not observe dementia in the first year, the risk of dementia in the cohort each
      year thereafter was about twice the risk in the population. After the first year,
      a 50% increase was observed in Alzheimer's disease in the cohort compared with
      that in the community. Although the incidence of dementia increased with
      increasing age, the standardized morbidity ratios decreased with increasing age.
      Age, sex (male), and second stroke were significant independent predictors of
      dementia in a multivariate Cox proportional hazards model. There was no effect of
      location or clinical severity of infarct on the rate of occurrence of dementia.

PMID- 8559367
TI  - Silent brain infarction in nonrheumatic atrial fibrillation. EAFT Study Group.
      European Atrial Fibrillation Trial.
AB  - BACKGROUND: Cerebral infarction associated with atrial fibrillation usually
      causes permanent neurologic disability, but several studies also reported
      patients with silent cerebral infarcts on CT. The clinical relevance of this
      findings is unknown, partly because of variable criteria for the diagnosis of
      "silent" brain infarction. METHODS: This report describes the frequency of silent
      brain infarcts in 985 patients with nonrheumatic atrial fibrillation, who shortly
      before suffered a symptomatic transient ischemic attach or nondisabling ischemic
      stroke, and evaluates the predictive value of silent infarcts for the future
      development of recurrent vascular events. RESULTS: Of 985 patients, 14% had CT
      evidence of brain infarcts not explainable by current or previous episodes of
      cerebral ischemia. In comparison with symptomatic infarcts, these silent infarcts
      were more often of the small deep lacunar type (odds ratio 5.1; 95% confidence
      interval 3.4-7.7). If silent and zone infarcts occurred, these often involved the
      territory of the posterior cerebral artery or the right hemisphere. The presence
      of a silent infarct at entry was associated with an increased risk of vascular
      events in general and of recurrent stroke in particular. This was due largely to
      the presence of multiple infarcts on CT. CONCLUSION: Silent infarcts reflect
      advanced vascular disease.

PMID- 8559368
TI  - Isolated infarcts of the pons.
AB  - We studied 36 patients with MRI-proven isolated acute pontine infarct.
      Corresponding to the constant territories of intrinsic pontine vessels, infarcts
      followed a predictable distribution, enabling us to delineate three main
      syndromes. Twenty-one patients had a ventral pontine infarct. Motor involvement
      varied from mild hemiparesis (ventrolateral pontine syndrome) to severe
      hemiparesis with bilateral ataxia and dysarthria (ventromedial pontine syndrome).
      In addition, three-fourths of the patients had clinical evidence for usually mild
      tegmental dysfunction. Eleven patients had a tegmental pontine infarct,
      presenting tegmental signs (eye movement disorders, cranial nerve palsies,
      sensory disturbances), and mostly mild motor deficits (tegmental pontine
      syndrome). Only four patients had alternating deficits, and these never
      corresponded to any of the so-called classic pontine syndromes. Infarcts in the
      medial and the extreme lateral tegmental territory were never observed in
      isolation, being always associated with cerebellar or larger (and multiple)
      infarctions in the posterior circulation. Four patients with a bilateral
      ventrotegmental pontine infarct presented with acute pseudobulbar palsy,
      bilateral motor deficits, and tegmental signs. The results of etiologic work-up
      emphasize the concept of basilar artery branch disease, which was the most common
      presumed cause of stroke (16/36, 44%). Basilar artery branch disease was
      particularly associated with large ventral infarcts, severe clinical
      symptomatology, progressive or fluctuating course, and local recurrence. Presumed
      small-artery disease (9/36, 25%) was usually associated with small ventral or
      tegmental infarcts and rapidly improving lacunar syndromes. Large-artery stenosis
      (8/36, 22%) and cardioembolism (1/36, 3%) were less common than in series of
      posterior circulation infarcts that include simultaneous pontine and extrapontine
      lesions. Recovery was good in two-thirds of the patients, the worse outcome being
      associated with large ventral infarcts.

PMID- 8559369
TI  - Brain edema after carotid surgery.
AB  - The postoperative hyperperfusion syndrome describes an abrupt increase in blood
      flow with loss of autoregulation in surgically reperfused brain. Reports
      described a spectrum of findings, including severe headache, transient ischemia,
      seizures, and intracerebral hemorrhage. Hypertension is common after carotid
      artery surgery and often plays a role in the pathophysiology. We now report five
      patients with severe white matter edema after carotid surgery, a finding not
      previously included in the hyperperfusion syndrome. Five to 8 days after carotid
      surgery and after hospital discharge, each patient developed hypertension,
      headache, hemiparesis, seizures, and aphasia or neglect due to severe white
      matter edema ipsilateral to the carotid surgery. One patient had a small
      hemorrhage within the edematous area. Hypertension was severe in four patients
      and moderate in one. The carotid artery was patent by ultrasound or angiography
      in each patient after surgery. Transcranial Doppler showed increased velocities
      ipsilateral to surgery in two patients and bilaterally in one. Computed
      tomographic abnormalities and neurologic signs resolved within 3 weeks in four of
      the five patients treated with antihypertensives and anticonvulsants. The fifth
      patient died from herniation secondary to massive edema. Brain edema with focal
      neurologic signs should be included as a serious but potentially reversible
      component of the postoperative hyperperfusion syndrome.

PMID- 8559370
TI  - Horner's syndrome after coronary artery bypass surgery.
AB  - We established the frequency of Horner's syndrome (HS) in 248 elective patients
      after coronary artery bypass surgery. Patients were evaluated neurologically pre-
      and post-operatively and 6 months after surgery. Nineteen patients (7.7%)
      developed unilateral HS postoperatively, 12 involving the left eye. The finding
      persisted in 10 patients (4%) at 6 months. When assessed 2 to 6 days, or 6
      months, postoperatively, HS tended to be isolated and not associated with C8/T1
      plexopathy. Among nondiabetic subjects, hypertensive patients had a higher
      frequency of HS than normotensive patients (10.6% versus 2.9%, p = 0.05). Among
      normotensive subjects, diabetic patients had a higher frequency than nondiabetic
      patients (15% versus 2.9%, p = 0.08). There was no association between HS, age,
      sex, internal mammary artery grafting, or length of cardiopulmonary bypass time.
      In summary, HS is a common and sometimes persistent complication of coronary
      artery bypass surgery. Hypertensive, and possibly diabetic, patients appear to be
      at greatest risk for developing HS.

PMID- 8559371
TI  - Unilateral spatial neglect recovery after sequential strokes.
AB  - We describe a patient who had sequential strokes in both hemispheres with a
      severe unilateral spatial neglect after a first right-sided parietal infarct and
      abrupt disappearance of the neglect after a second left-sided frontal infarct.
      The first lesion involve the caudalmost right angular gyrus (area 39), whereas
      the second lesion involved the left frontal eye field (area 8) and surrounding
      cortex. Those two cortical areas are assumed to have a pivotal role in modulating
      both shifts of attention within extrapersonal space and saccadic eye movements
      through their connections with subcortical structures, in particular, superior
      colliculi and thalamic nuclei. Our case supports the existence of a distributed
      anatomic-functional network in subserving directed spatial attention.

PMID- 8559372
TI  - Chronic lymphocytic leukemia and the central nervous system: a clinical and
      pathological study.
AB  - Chronic lymphocytic leukemia is the most common human leukemia but infrequently
      causes neurologic symptoms. We have reviewed all previously reported cases of
      chronic lymphocytic leukemia in the CNS along with three new cases; one patient
      was diagnosed antemortem and treated with immediate improvement and 4-year
      survival. In addition, we reviewed all autopsy cases since 1972 and available
      lumbar puncture data on patients with chronic lymphocytic leukemia admitted to
      the Massachusetts General Hospital. Invasion of the CNS by chronic lymphocytic
      leukemia often leads to confusional state, meningitis with cranial nerve
      abnormalities, optic neuropathy, or cerebellar dysfunction. Lumbar puncture shows
      a lymphocytosis consisting of monoclonal B cells, but CSF cytology studies are of
      limited value in establishing the diagnosis. Long-term survival may be related to
      the stage of chronic lymphocytic leukemia at the time of CNS disease and may be
      associated with intrathecal chemotherapy. A mild, asymptomatic infiltration of
      the brain, frequently noted in late-stage chronic lymphocytic leukemia in autopsy
      series, may explain the CSF lymphocytosis in some patients with late-stage
      chronic lymphocytic leukemia.

PMID- 8559373
TI  - Primary angiitis of the central nervous system associated with cerebral amyloid
      angiopathy: report of two cases and review of the literature.
AB  - Early diagnosis is essential for the effective management of primary angiitis of
      the CNS (PACNS), but the presence of cerebrovascular amyloid angiopathy (CAA) may
      complicate the pathologic diagnosis since nonvasculitic inflammatory reactions
      can accompany CAA. We report two patients with PACNS associated with CAA in whom
      the progression of symptoms ceased during combined
      corticosteroid/cyclophosphamide therapy. One patient had prominent eosinophilic
      vasculitis and eosinophilic CSF pleocytosis. Based on review of reported cases,
      features supporting the diagnosis of symptomatic vasculitis in these patients
      include subacute progression of mental status changes and multifocal deficits,
      elevated ESR and CSF protein, and multifocal nonhemorrhagic lesions on imaging
      studies. We conclude that combined disease (PACNS/CAA) is similar to PACNS and
      probably occurs more frequently than expected by coincidence. The presence of CAA
      should not alter the treatment strategy in patients presenting with symptoms and
      laboratory studies consistent with PACNS.

PMID- 8559374
TI  - Elevated intracranial venous pressure as a universal mechanism in pseudotumor
      cerebri of varying etiologies.
AB  - Pseudotumor cerebri (PTC), or idiopathic intracranial hypertension, is a syndrome
      associated with multiple clinical conditions. We hypothesize that most if not all
      etiologies result in an increase in intracranial venous pressure as a final
      common pathway. We studied 10 patients with PTC. Five had dural venous outflow
      obstruction as demonstrated by venography, and the five remaining patients had
      normal venous anatomy. Pressure measurements, made during venography in eight
      patients, all showed elevated pressures. Pressure measurements in the superior
      sagittal sinus ranged from 13 to 24 mm Hg (mean, 16.6 mm HG). Patients with
      obstruction tended to have a high pressure gradient across the stenotic segment.
      Five patients with normal dural venous anatomy had elevated right atrial
      pressures (range, 6 to 22 mm Hg; mean, 11.8 mm Hg), which were transmitted up to
      the intracranial venous sinuses. Endovascular techniques, including angioplasty
      and infusion of thrombolytic agents in some cases, improved outlet obstruction
      from a hemodynamic perspective but were ineffective in consistently and reliably
      alleviating the clinical manifestations of PTC. Patients in both groups tended to
      respond well to conventional CSF diversion procedures. Our study suggests that
      elevated intracranial venous pressure may be a universal mechanism in PTC of
      different etiologies. This elevated venous pressure leads to elevation in CSF and
      intracranial pressure by resisting CSF absorption. Although the mechanism leading
      to venous hypertension in the presence of outflow obstruction is obvious, the
      etiology of increased intracranial and central systemic venous pressure in PTC
      remains obscure.

PMID- 8559375
TI  - Docetaxel neuropathy.

PMID- 8559376
TI  - Low-grade oligodendroglioma responds to chemotherapy.
AB  - We administered chemotherapy in standard and intensified formulations of
      procarbazine, lomustine (CCNU), and vincristine to nine symptomatic patients with
      low-grade oligodendroglioma. Eight patients were treated with chemotherapy at
      presentation and one was treated for a recurrence after radiotherapy had failed.
      All patients improved by clinical or MRI criteria, or both. No patient
      deteriorated while in therapy and the responses were sustained without
      radiotherapy for a median of 35 months (range, 22-45) in all surviving patients
      treated at presentation. Chemotherapy was well tolerated; all patients developed
      myelosuppression, but only those receiving the intensified regimen required dose
      reduction or premature discontinuation of treatment. As with recurrent and
      anaplastic oligodendroglioma, low-grade oligodendroglioma responds to
      chemotherapy.

PMID- 8559377
TI  - Mutations in American families with spinocerebellar ataxia (SCA) type 3: SCA3 is
      allelic to Machado-Joseph disease.
AB  - We identified an expansion of the CAG trinucleotide repeat in the coding region
      of the Machado-Joseph disease gene in 7 of 24 American families diagnosed with
      autosomal dominant ataxia. All affected individuals were heterozygous for an
      expanded allele that ranged from 67 to more than 200 CAG repeats, whereas the
      normal allele had 14 to 33 repeats. In contrast to the Azorean-Portuguese origins
      of Machado-Joseph disease, the two largest American families were of German and
      Dutch-African descent. Clinical, pathologic, and genetic evaluations suggest that
      American families with spinocerebellar ataxia type 3 differ from those with
      Machado-Joseph disease by their ethnic origins, predominant spinopontine atrophy,
      lack of dystonic features, and larger CAG repeat expansion.

PMID- 8559378
TI  - Frequency of spinocerebellar ataxia type 1, dentatorubropallidoluysian atrophy,
      and Machado-Joseph disease mutations in a large group of spinocerebellar ataxia
      patients.
AB  - The spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative
      disorders varying in both clinical manifestations and mode of inheritance. Six
      different genes causing autosomal dominant SCA are mapped: SCA1, SCA2, Machado
      Joseph disease (MJD)/SCA3, SCA4, SCA5, and dentatorubropallidoluysian atrophy
      (DRPLA). Expansions of an unstable trinucleotide CAG repeat cause three of these
      disorders: SCA type 1 (SCA1), MJD, and DRPLA. We determine the frequency of the
      SCA1, DRPLA, and MJD mutations in a large group of unrelated SCA patients with
      various patterns of inheritance and different ethnic backgrounds. We studied 92
      unrelated SCA patients. The frequency of the SCA1 mutation was 3% in the overall
      patient group and 10% in the non-Portuguese dominantly inherited SCA subgroup. We
      found that DRPLA mutation in only one Japanese patient, who was previously
      diagnosed with this disease. We identified the MJD mutation in 41% of the overall
      patient group, which included 38 autosomal dominant kindreds of Portuguese
      origin; the frequency of the MJD mutation among the non-Portuguese dominantly
      inherited cases was 17%. These results suggest that SCA may be occasionally
      caused by the SCA1 mutation and rarely caused by the DRPLA mutation and that, to
      date, the MJD mutation seems to be the most common cause of dominantly inherited
      SCA. Finally, our results suggest that recessively inherited cases of SCA are not
      caused by the known trinucleotide repeat expansions.

PMID- 8559379
TI  - Association of the mitochondrial 8344 MERRF mutation with maternally inherited
      spinocerebellar degeneration and Leigh disease.
AB  - We report previously undescribed or atypical clinical and biochemical
      manifestations of the mitochondrial DNA MERRF mutation at nucleotide 8344 in
      members of a multigenerational family with maternally inherited, highly variable
      neurodegenerative disorder. The more profound neurologic abnormalities include
      Leigh disease, spinocerebellar degeneration, and atypical Charcot-Marie-Tooth
      disease.

PMID- 8559380
TI  - MELAS: Clinical and pathologic correlations with MRI, xenon/CT, and MR
      spectroscopy.
AB  - We describe the clinical, imaging, and pathologic findings in a patient with
      mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
      (MELAS). The patient experienced her first stroke-like episode at age forty-four.
      Brain MRI, obtained at symptom onset, at 3 weeks, and at 1 year, revealed
      migrating T2-weighted hyperintensities in the temporal/parietal and occipital
      cortices and later revealed atrophy. Abnormal cerebrovascular reserve was evident
      on xenon/CT four days after the first MRI. MR spectroscopy at 1 year revealed
      increased lactate in both the occipital and temporal lobes. Histologic sections
      demonstrated spongy degeneration of the cortex that was most prominent at the
      crests of the gyri. Electron microscopy of the blood vessels showed increased
      numbers of abnormal mitochondria within the vascular smooth muscle and in
      endothelial cells. We hypothesize that the stroke-like episodes in MELAS may be
      due to impaired autoregulation secondary to the impaired metabolic activity of
      mitochondria in the endothelial and smooth muscle cells of blood vessels.

PMID- 8559381
TI  - Neuronal loss in the medullary reticular formation in myotonic dystrophy: a
      clinicopathological study.
AB  - Respiratory insufficiency occurs frequently in patients with myotonic dystrophy
      (MyD). We have performed a quantitative study of neurons linked to respiratory
      function in the dorsal central medullary nucleus (DCMN), the ventral central
      medullary nucleus (VCMN), and the subtrigeminal medullary nucleus (SMN) in seven
      patients with MyD and eight age-matched controls. Alveolar hypoventilation of the
      central type occurred in three of the MyD patients but not in the remaining MyD
      patients or controls. The densities of neurons of the DCMN, the VCMN, and the SMN
      in MyD patients with hypoventilation were significantly lower than in MyD without
      hypoventilation and controls. These data suggest the neuronal loss of the DCMN,
      VCMN, and SMN is associated with the presence of hypoventilation in MyD and may
      be an important feature of MyD.

PMID- 8559382
TI  - [123I] beta-CIT/SPECT imaging demonstrates bilateral loss of dopamine
      transporters in hemi-Parkinson's disease.
AB  - We have used in vivo single-photon emission computed tomography (SPECT) of the
      dopamine transporter with 2 beta-carboxymethoxy-3 beta-(4-iodophenyl)tropane
      ([123I] beta-CIT) to investigate striatal dopamine transporter loss in patients
      with early Parkinson's disease (PD). Striatal uptake of ([123I] beta-CIT was
      compared in eight early-PD patients with exclusively hemi-parkinsonism and eight
      age- and sex-matched healthy subjects. [123I] beta-CIT striatal uptake was
      reduced by approximately 53% contralateral and by 38% ipsilateral to the
      clinically symptomatic side in the hemi-PD patients, compared with the mean
      striatal uptake in age- and sex-matched healthy subjects. The relative reduction
      in [123I] beta-CIT uptake in the hemi-PD patients was greater in the putamen than
      in the caudate. These data demonstrate that SPECT imaging of the dopamine
      transporter with [123I] beta-CIT can identify patients with PD at the onset of
      motor symptoms and suggest that this technique also may be useful in identifying
      individuals with developing dopaminergic pathology before onset of motor
      symptoms.

PMID- 8559383
TI  - Differential effect of aspirin versus warfarin on clinical stroke types in
      patients with atrial fibrillation. Stroke Prevention in Atrial Fibrillation
      Investigators.
AB  - The Stroke Prevention in Atrial Fibrillation II study compared the efficacy and
      safety of aspirin and warfarin in patients with atrial fibrillation. Three
      neurologists, blinded to patient therapy, categorized the pathophysiology of
      ischemic strokes that occurred in the trial based on predetermined clinical
      criteria. Upon analyzing the patients being treated with these two drugs,
      warfarin proved significantly more effective than aspirin in preventing
      cardioembolic strokes (p = 0.005) and strokes of uncertain pathophysiology (p =
      0.01). There was no significant difference in the efficacy for prevention of
      noncardioembolic strokes.

PMID- 8559384
TI  - Lamotrigine-induced rash in children.
AB  - Of 68 children treated with lamotrigine, a new antiepileptic medication, five
      developed a rash. One child developed Stevens-Johnson syndrome on lamotrigine
      monotherapy. Of the five patients with the rash, three were admitted to the
      hospital (two to the intensive care unit). All recovered completely, but one
      child had a recurrence of the rash within 30 minutes of reexposure to lamotrigine
      after 6 months.

PMID- 8559385
TI  - Plasmapheresis in Rasmussen's encephalitis.
AB  - Rasmussen's encephalitis (RE) is a progressive childhood disorder characterized
      by intractable focal seizures, hemiplegia, dementia, and inflammatory
      histopathology. The process is typically limited to one cerebral hemisphere. We
      report four patients with pathologically confirmed RE who were treated with
      repeated plasmapheresis. Three patients exhibited repeated, dramatic, transient
      responses to plasmapheresis, manifested by reduced seizure frequency and improved
      neurologic function. One patient exhibited marginal improvement after treatment
      with plasmapheresis. These observations indicate that circulating factors, likely
      autoantibodies, are pathogenic in at least some patients with RE and suggest that
      RE is an autoimmune disease. Plasmapheresis may be a useful adjunctive therapy in
      status epilepticus, and can also aid in assessment of residual function in the
      diseased hemisphere before surgical resection.

PMID- 8559386
TI  - Chronic steroid-responsive encephalitis without autoantibodies to glutamate
      receptor GluR3.
AB  - Autoantibodies to GluR3, an AMPA glutamate receptor subtype, may be a cause of
      chronic unilateral encephalitis (Rasmussen's syndrome). We report a woman with
      chronic left hemisphere encephalitis whose partial seizures, aphasia, and motor
      weakness are highly responsive to intermittent steroids and cyclophosphamide. Her
      serum and CSF were negative for antibodies to GluR3 by both immunoblot and
      immunocytochemical analysis of cells transfected with GluR3 cDNA, indicating that
      separate immune-mediated processes may be involved in some cases of chronic
      encephalitis.

PMID- 8559387
TI  - Reversible encephalopathy with cerebral vasospasm in a Guillain-Barre syndrome
      patient treated with intravenous immunoglobulin.
AB  - We report a patient with a reversible multifocal encephalopathy that developed 3
      days after completion of treatment with intravenous immunoglobulin for Guillain
      Barre syndrome. Magnetic resonance imaging showed reversible bioccipital white
      matter changes, and transcranial Doppler demonstrated transiently increased flow
      rates in all major cerebral arteries. We conclude that intravenous immunoglobulin
      therapy caused cerebral arterial vasospasm and a reversible encephalopathy.

PMID- 8559389
TI  - Late juvenile metachromatic leukodystrophy treated with bone marrow
      transplantation; a 4-year follow-up study.
AB  - We treated a 28-year-old woman who had metachromatic leukodystrophy with bone
      marrow transplantation. Leukocyte arylsulfatase A levels increased to the donor's
      range after successful graft. Motor and sensory nerve conduction values did not
      change significantly in the 4 years after the transplant, and subcortical white
      matter lesions, as shown on MRI, remained stable during that period of time. The
      results, after 4 years of follow-up, indicate that the disease has not progressed
      and signs and symptoms are stabilized.

PMID- 8559388
TI  - Cyclosporine-associated mutism in liver transplant patients.
AB  - Four liver transplant recipients treated with cyclosporine developed a reversible
      neurologic syndrome characterized by a speech disorder leading to mutism. This
      complication, previously reported in a few liver transplant recipients treated
      with the immunosuppressive drug FK506, had not been described with cyclosporine.
      Recognition of this syndrome should prompt withdrawal of the drug and avoidance
      of unnecessary diagnostic procedures.

PMID- 8559390
TI  - Dystonic postures generated from complex repetitive discharges.
AB  - We report a woman with a chronic inflammatory myopathy who developed muscle
      stiffness and dystonic postures of both upper extremities. Electromyography
      demonstrated that involuntary complex repetitive discharges of muscle caused the
      posture. Rare cases of dystonic posturing may be of peripheral, and not central
      system, origin.

PMID- 8559391
TI  - Myokymic discharges of the tongue after radiation to the head and neck.
AB  - We report two patients who developed myokymic discharges of the tongue after
      radiation therapy. One patient had carcinoma of the nasopharynx, and the other
      had a chemodectoma of the middle ear. Radiation therapy may damage the
      hypoglossal nerve and cause myokymia of the tongue, similar to myokymic
      discharges associated with brachial plexopathies after radiation therapy.

PMID- 8559392
TI  - Botulinum toxin therapy, immunologic resistance, and problems with available
      materials.
AB  - Botulinum toxin is a valuable technology for the treatment of regional movement
      disease. High-dose applications ( > 100 LD50 units per injection cycle) have been
      associated with sensitization that renders further therapeutic injections
      ineffective. The true incidence of sensitization is probably underestimated by
      the mouse bioassay. Other immunotypes of botulinum toxin have been effective in
      producing some therapeutic benefit; however, duration of action (botulinum toxin
      type F) and lower potencies may make these less attractive alternatives than
      botulinum type A. Increased specific activity botulinum toxin may be a method to
      reduce antigen exposure and mitigate against immunoresistance associated with
      dystonia therapy. Limiting the dose to < or = 100 LD50 units per injection cycle
      may limit this complication in the interim.

PMID- 8559393
TI  - Melatonin replacement corrects sleep disturbances in a child with pineal tumor.
AB  - A child with a germ cell tumor involving the pineal region had marked suppression
      of melatonin secretion associated with severe insomnia. Exogenous melatonin (3 mg
      in the evening) for 2 weeks restored sleep continuity, as demonstrated by
      objective monitoring of rest-activity cycles. This case report provides direct
      evidence of the essential role of melatonin in normal sleep.

PMID- 8559394
TI  - Bilateral ocular neuromyotonia: oculographic correlations.
AB  - We observed bilateral ocular neuromyotonia in a 45-year-old woman previously
      treated for a pituitary adenoma. She experienced episodic diplopia attributable
      to dysfunction of muscles innervated by both oculomotor nerves. Oculography
      demonstrated episodes of tonic adduction with slowing and restriction of saccades
      in all directions, but no oscillatory component. A combination of impaired phasic
      firing in agonist muscles and tonic contraction of antagonist muscles explains
      the paroxysms of eye movement limitation in this disorder.

PMID- 8559395
TI  - Vomiting out of proportion to dizziness in ischemic brainstem strokes.

PMID- 8559396
TI  - Transient hemiballism/hemichorea due to an ipsilateral subthalamic nucleus
      infarction.

PMID- 8559397
TI  - Headaches after inadvertent lumbar puncture during bone marrow harvest.

PMID- 8559398
TI  - Recurrent neck pain as a variant of migraine: a case report.

PMID- 8559399
TI  - Trigeminal sensory neuropathy in connective tissue disease: evidence for the site
      of the lesion.

PMID- 8559400
TI  - Exacerbation of myasthenia gravis associated with cocaine use.

PMID- 8559401
TI  - Reversible myoclonus, tremor, and ataxia in a patient exposed to methyl ethyl
      ketone.

PMID- 8559402
TI  - Prion analogues and twin studies in Parkinson's disease.

PMID- 8559403
TI  - Proving the worth of neurologists.

PMID- 8559404
TI  - Assessment of brain SPECT. Report of the Therapeutics and Technology Assessment
      Subcommittee of the American Academy of Neurology.
AB  - Brain SPECT is beginning to emerge as a helpful tool in the evaluation of a
      variety of neurologic disorders (table). Studies are needed to further define the
      cost-effectiveness of this modality.

PMID- 8559405
TI  - Subcutaneous sumatriptan and the migraine aura.

PMID- 8559406
TI  - M-Bacod as first treatment for primary CNS lymphoma.

PMID- 8559407
TI  - Encephalopathies after levamisole therapy.

PMID- 8559408
TI  - Rubral tremor.

PMID- 8559409
TI  - Saccade-induced nystagmus.

PMID- 8559410
TI  - Primary progressive aphasia and frontal lobe involvement.

PMID- 8559411
TI  - Ergotamine-induced headache associated with cluster headache.

PMID- 8559412
TI  - Antiphospholipid antibodies and Binswanger's disease.

PMID- 8559413
TI  - Antiphospholipid antibodies and Binswanger's disease.

PMID- 8559414
TI  - Localizing cognitive functions in the brain.

PMID- 8559415
TI  - Muscles of a different 'color': the unusual properties of the extraocular muscles
      may predispose or protect them in neurogenic and myogenic disease.
AB  - The rules that govern many aspects of skeletal muscle structure and function are
      very different for the extraocular muscle allotype. The myoblast lineages present
      in the extraocular muscle primordia are permissive for generation of an unusually
      wide range of fiber types. The balance that is struck between genetic
      specification and activity dependent factors in shaping fiber phenotype to suit
      the demands of complex visuomotor systems is not yet well defined. Because
      skeletal muscle has high energy demands, diversity in fiber types is needed to
      maximize efficiency; greater diversity in fiber composition then indicates a more
      diverse functional repertoire. Together, the characteristics of small motor unit
      size, precise dependence of muscle force upon motor neuron discharge rate, high
      contractile speed but low tension development, and contractile protein
      heterogeneity contribute toward the high precision and diversity that is required
      for eye movements. Finally, the structural and functional characteristics and
      plasticity of the individual extraocular muscle fiber types play an important
      role in determining their response to disease or manipulation. The lack of
      uniform responses across the muscle allotypes in disease, or in response to
      pharmaceutical or surgical interventions, requires that we obtain a better
      understanding of the fundamental differences that exist between muscle groups.

PMID- 8559416
TI  - Extracorporeal 'phantom' tics in Tourette's syndrome.
AB  - Some tics are intentional movements made in an attempt to diminish uncomfortable
      sensations. These sensations, sometimes termed sensory tics, are focal and
      usually arise in the part of the body involved in the subsequent motor act. We
      report a patient whose sensations associated with tics were felt in other people
      and in objects. The discomfort associated with his out-of-body sensations was
      temporarily relieved by touching or scratching the object involved. The
      definition of premonitory sensations should be expanded to include extracorporeal
      sensations, and a history of external sensations should be sought in patients
      with Tourette's syndrome. Theories on the generation of tics must incorporate an
      explanation for extracorporeal sensations.

PMID- 8559417
TI  - Machado-Joseph disease and SCA3: the genotype meets the phenotypes.

PMID- 8559418
TI  - Does the number of seizures before treatment influence ease of control or
      remission of childhood epilepsy? Not if the number is 10 or less.
AB  - Using a population-based regional cohort of 479 children with epilepsy, we
      studied the effect of the number of pretreatment afebrile seizures on seizure
      control and remission. The number of pretreatment seizures varied from 1 to 20.
      For the first 10 pretreatment seizures, there was no significant difference or
      trend in (1) the proportion of children who were seizure free long enough to
      attempt stopping medication (mean, 70%), (2) the number of breakthrough seizures
      before control was achieved, or (3) the proportion of children who were seizure
      free after stopping medication for the first time (mean, 70%). More patients with
      more than 10 pretreatment seizures had complex partial seizures (59%) than those
      with 10 or fewer seizures (16%) (p < 0.00001). We conclude that there does not
      appear to be any penalty for seizure control or early remission of epilepsy if
      medication is delayed for up to 10 pretreatment seizures.

PMID- 8559419
TI  - Unilateral blinking: a lateralizing sign in partial seizures.
AB  - BACKGROUND: Despite lateralizing signs, clinical lateralization of partial
      seizures may be difficult. We evaluated the usefulness of ictal unilateral
      blinking as a new lateralizing sign. METHODS: We retrospectively searched our
      seizure database over a 30-month period and collected videotapes of patients with
      ictal unilateral blinking. After initial review, we excluded patients in whom
      blinking was not clearly unilateral and those in whom it was accompanied by
      simultaneous facial clonic activity or mouth deviation. All patients underwent
      prolonged EEG-video monitoring. RESULTS: We identified 14 patients who met the
      above criteria, for a frequency of 1.5%. Age ranged from 18 months to 50 years
      (mean, 21.6). There were 11 males and 3 females. Unilateral blinking occurred 0
      to 37 seconds (mean, 10) after clinical onset and was visible for 1 to 37 seconds
      (mean, 17). In 10 patients, other lateralizing signs were present. All patients
      had partial epilepsy, localized by surface EEG in 10 and by additional invasive
      EEG in four--nine were left hemisphere (four temporal, four frontal, one not
      further localized), three right hemisphere (two temporal, one frontal), and two
      undetermined. Of the 12 patients whose epileptogenic zone was lateralized,
      blinking was ipsilateral in 10 and contralateral in two. The predictive value of
      unilateral blinking was 83% against EEG localization. CONCLUSION: Unilateral
      blinking is a relatively uncommon but reliable lateralizing sign in partial
      seizures, usually indicating an ipsilateral epileptogenic zone.

PMID- 8559420
TI  - Efficacy and safety of add-on divalproex sodium in the treatment of complex
      partial seizures. The M88-194 Study Group.
AB  - We studied the efficacy of divalproex sodium in patients with complex partial
      seizures taking concomitant carbamazepine or phenytoin as monotherapy. Patients
      were selected because of inadequate seizure control by current therapy. The
      primary efficacy measure was median reduction of seizure frequency during add-on
      treatment compared with baseline. A secondary measure was the percentage of
      patients achieving > or = 50% reduction in seizure frequency. In the intent-to
      treat analysis (137 patients), divalproex-treated patients experienced a median
      reduction of 7.9 complex partial seizures per 8 weeks compared with 2.5 in the
      placebo group (p = 0.001). Also, 38% of divalproex-treated patients completed the
      study with a seizure reduction of > or = 50% compared with 19% receiving placebo
      (p = 0.011). Six divalproex- and one placebo-treated patient became free of
      complex partial seizures. We conclude that divalproex sodium is an effective drug
      for treating patients with complex partial seizures.

PMID- 8559421
TI  - A double-blind, placebo-controlled study of vigabatrin three g/day in patients
      with uncontrolled complex partial seizures. Vigabatrin Protocol 024 Investigative
      Cohort.
AB  - This study compared the efficacy and tolerability of vigabatrin 3/day as add-on
      therapy with that of placebo in patients with focal epilepsy whose complex
      partial seizures were difficult to control with established antiepilepsy drug
      therapy. We enrolled 203 patients; 182 (90 placebo; 92 vigabatrin) received drug
      therapy under double-blind conditions. We increased the daily dosage to 2.5 g/day
      during a 4-week titration segment and maintained it at 3 g/day during the 12-week
      maintenance segment. By analyses we found a statistically significant lower
      frequency of seizures (complex seizures plus partial seizures secondarily
      generalized) at the end of the study for patients receiving vigabatrin than for
      those receiving placebo. The median monthly frequency was reduced by three
      seizures per 28 days in the placebo group (baseline, 8.3; end of study, 7.5) (p =
      0.0002). Therapeutic success (a 50% reduction from baseline in mean monthly
      seizure frequency) was attained in 40 of the vigabatrin patients (43%) compared
      with 17 of those treated with placebo (19%) (p < 0.001). Vigabatrin significantly
      increased the mean number of seizure-free days per 28 days (2.2 days) compared
      with placebo (0.5 days) (p = 0.0024). Mean trough serum vigabatrin concentration
      during therapy was 8.6 +/- 7.7 micrograms/ml. The oral clearance of vigabatrin
      was determined to be 7.8 L/hr, and the elimination half-life was 8.4 hours. No
      clinically important changes in MRI, evoked potential, or other laboratory tests
      were noted during vigabatrin treatment. The results of this study indicate that 3
      g/day vigabatrin is more effective than placebo as add-on therapy. Vigabatrin was
      well tolerated, compliance was high with twice-daily administration, and therapy
      did not result in clinically relevant drug interactions.

PMID- 8559422
TI  - Use of antiepileptic drugs in a community-dwelling Dutch population.
AB  - We compared the treatment policy for patients with epilepsy in six Dutch cities,
      comprising 302, 149 inhabitants, with the treatment policies of a secondary
      referral center (a university hospital) and tertiary referral centers (outpatient
      departments of epilepsy centers). By comparing the prevalence of individuals
      receiving antiepileptic drugs in the six cities with the epidemiologic data for
      epilepsy in Rochester, Minnesota, we concluded that prescription data offer a
      suitable means by which to estimate the prevalence of epilepsy in a community. To
      compare prescriptions in cases of polytherapy, we normalized data by using
      defined daily doses published by the WHO Collaborating Center for Drugs
      Statistics Methodology and the Nordic Council on Medicines and concluded that the
      defined daily doses of antiepileptic drugs should be further elaborated. There is
      a need to obtain complete dose-response curves of equivalent antiepileptic drugs
      in humans. The trend of drugs use found in the six cities, the university
      hospital, and the epilepsy centers is, however, in accord with the expectations
      regarding primary, secondary, and tertiary referral centers.

PMID- 8559423
TI  - Delayed-onset progressive movement disorders after static brain lesions.
AB  - We studied 53 patients (64% females) with static brain lesions who developed
      progressive movement disorders. Of these, 50 (94%) had dystonia, 17 (32%) tremor,
      eight (15%) parkinsonism, seven (13%) myoclonus, and three (6%) chorea. The
      precipitating insults included perinatal hypoxia/ischemia in 22 (42%), stroke in
      12 (23%), head injury in eight (15%), encephalitis in eight (15%), and carbon
      monoxide poisoning, kernicterus, and radiation necrosis in one patient (2%) each.
      Among the 30 patients with initial insult occurring at age 2 years or younger
      (Infant group), distribution of dystonia at follow-up was focal in three (10%),
      segmental in eight (27%), unilateral in 10 (33%), and generalized in nine (30%).
      The mean latency between the original injury and onset of movement disorder was
      25.5 +/- 16.7 years. Among the nine patients who developed dystonia after an
      insult occurring between ages 6 and 17 (Childhood group), the distribution of
      dystonia at follow-up was segmental in two (33%) and unilateral in seven (78%);
      the mean latency of dystonia onset was 4.9 +/- 7.8 years. Of the 14 patients in
      the Adult group (injury at age 25 or older), 11 developed dystonia, two developed
      parkinsonism, and one had carbon monoxide encephalopathy and parkinsonism. The
      distribution of dystonia in the 11 patients at follow-up was segmental in three
      (27%) and unilateral in eight (73%). The mean latency of movement disorder onset
      in the 14 patients of the Adult group was 2.5 +/- 4.9 years. No individuals in
      the Childhood or Adult groups became left-hand dominant; by comparison, nine of
      the 30 individuals in the Infant group became left-handed. In conclusion, brain
      injury at a young age is associated with a longer latency to onset of subsequent
      movement disorder, a greater tendency to development of generalized dystonia, and
      a greater probability of altered handedness. These tendencies may result from
      differences in age-related neuroplasticity.

PMID- 8559424
TI  - Thalamic tremor: case reports and implications of the tremor-generating
      mechanism.
AB  - We report two patients with unilateral resting and postural tremor of the upper
      limb as a delayed manifestation of thalamic stroke. Neuroradiologic examination
      showed a lesion in the posterolateral thalamic region in both patients, but with
      no obvious involvement of the brainstem, the cerebellum, or the cerebellar
      outflow tract to the thalamic ventrolateral nucleus.

PMID- 8559425
TI  - Lack of progression of neurologic deficit in survivors of paralytic polio: a 5
      year prospective population-based study.
AB  - We completed a prospective, population-based cohort study of polio survivors in
      Olmsted County, Minnesota, between 1986 and 1993. We identified 50 individuals
      who had had paralytic polio between 1935 and 1960, as representative of all 300
      cases of paralytic polio in the county. We completed detailed quantitative
      clinical and electrophysiologic studies at entry and after 5 years. These studies
      demonstrated stable neuromuscular function within the cohort, although 60% of the
      individuals were symptomatic. In two-thirds of the symptomatic patients, the
      causes of their symptoms were unrelated to earlier polio. For the 20% of patients
      who had unexplained muscle pain, perception of weakness, and fatigue, a
      mechanical disorder most likely underlies their symptoms.

PMID- 8559426
TI  - Nerve conduction measures in mild diabetic neuropathy in the Early Diabetes
      Intervention Trial: the effects of age, sex, type of diabetes, disease duration,
      and anthropometric factors. Tolrestat Study Group for the Early Diabetes
      Intervention Trial.
AB  - We evaluated nerve conduction measures at baseline from 429 patients enrolled in
      a multicenter diabetic neuropathy study. We defined neuropathy by using recently
      proposed recommendations but included only patients who had measurable sural and
      peroneal responses and quantitative vibration thresholds. Patients with type II
      diabetes were older than type I patients (54.5 versus 39.1 years), were heavier
      (body mass index [BMI] of 30.9 versus 25.5 kg/m2, and in general had lower evoked
      amplitudes. The effects of diabetes type upon nerve conduction measures
      disappeared when age and BMI were included in regression models. The men had
      lower amplitudes and conduction velocities and longer latencies than the women.
      The effect of gender was greatly reduced when height was included in the
      regression models, but gender continued to be a significant predictor of median
      sensory amplitude, most conduction velocities, and most latencies in these
      models. The relationships between nerve conduction measures and age, sex, and
      anthropometric factors were similar for patients with type II, but not those with
      type I, diabetes to the relationships reported for normal subjects. This may be a
      result of greater homogeneity with respect to degree of neuropathy for type II
      patients than for type I patients. These findings are important in designing and
      interpreting clinical studies of diabetic neuropathy.

PMID- 8559427
TI  - Rasmussen's encephalitis and the new hat.

PMID- 8559428
TI  - A questionnaire study of 138 patients with restless legs syndrome: the 'Night
      Walkers' survey.
AB  - After verifying the diagnosis of restless legs syndrome (RLS) in 105 patients who
      are part of a nationwide support group, we undertook a telephone survey of their
      symptomatology. We then compared the answers with those of 33 of our own RLS
      patients who had undergone a neurologic examination and had a periodic limb
      movement in sleep (PLMS) index of > 5 (number per hours of sleep). Although RLS
      has generally been considered to be a condition of middle to older age, the
      results for the support group, and for our patients, are similar in that more
      than a third of the patients in each group experienced their first symptoms
      before the age of 10. Initial lack of diagnosis or misdiagnosis by a physician
      were common and the symptoms were commonly thought to be psychogenic whatever the
      age of onset. In some cases, young age-onset RLS was severe from the start. For
      younger age-onset patients whose symptoms were severe enough to seek immediate
      medical attention, confounding or misdiagnosis included "growing pains" and
      attention deficit hyperactivity disorder. However, medical attention was
      generally not sought until the fourth decade. Most respondents stated that this
      was because their symptoms were mild at onset and then progressed. In the older
      age-onset patients, misdiagnoses also included skin irritation, arthritis, and
      malingering. A total remission of symptoms of a month or more was present in at
      least 15% of the individuals in all groups surveyed. More than 50% of the
      respondents know of one or more first-degree relatives affected by RLS. Five of
      our 33 patients had RLS initially triggered either by diabetic peripheral
      neuropathy or lumbosacral radiculopathy.

PMID- 8559429
TI  - Liver function disturbances in Guillain-Barre syndrome: a prospective
      longitudinal study in 100 patients. Dutch Guillain-Barre Study Group.
AB  - In 100 consecutive patients with Guillain-Barre syndrome, we assessed liver
      function on admission and at fixed intervals after either intravenous
      immunoglobulin (IgIV) or plasma-exchange (PE) treatment. On admission, 38% showed
      a plasma alanine aminotransferase elevation, gamma glutamyl transferase
      elevation, or both or more than 1.5 times the upper limit of normal. Ten of these
      patients had serologic evidence of recent cytomegalovirus infection. The
      remaining 28 patients were negative for other known causes of liver damage,
      including infection with Epstein-Barr virus or hepatitis A, B, and C; alcohol
      abuse; hepatotoxic drugs; recent surgery; and concurrent liver disease. In a
      hospital control group of 100 consecutive patients with subarachnoid hemorrhage,
      only 5 had unexplained liver function disturbances on admission (p < 0.0001). In
      the IgIV-treated group, the percentage of patients with elevated liver function
      tests increased from 35% before to 69% shortly after treatment at 2 weeks
      postadmission (p < 0.005). In the PE-treated group, this percentage decreased
      somewhat from 41% to 36% (not significant). There was also a significant rise in
      median plasma activity of the various liver enzymes in the IgIV group. At 1
      month, however, significant difference had disappeared. At 3 and 6 months, the
      percentage of patients with liver function disturbances reached a significantly
      lower level in both treatment groups compared with the time of admission. We
      concluded that many patients with Guillain-Barre syndrome had mild liver function
      disturbances without obvious cause. In addition, IgIV treatment was associated
      with mild transient liver function disturbances through an unknown mechanism.

PMID- 8559430
TI  - [Electron microscopic analysis of possible ultrastructural damage to spermatozoa
      after preparation by various methods].
AB  - We investigated the possibility of ultrastructural damage to human spermatozoa
      induced by different sperm preparation techniques. Ejaculates from 20
      normozoospermic men were divided into equal aliquots and processed by glass wool
      filtration, Percoll density gradient centrifugation, and a simple two step
      centrifugation procedure which served as a control. Ultrastructural damage was
      assessed by scanning electron microscopy. Compared with Percoll density gradient
      centrifugation, glass wool filtration yielded a significantly increased
      proportion of intact acrosomes (p < 0.05). However, both preparations gave
      significantly better results than control (p < 0.001 and p < 0.01 for glass wool
      filtration and Percoll centrifugation, respectively). The conspicuous bending of
      sperm tails after Percoll centrifugation has a yet unknown importance. In
      conclusion, both glass wool filtration and Percoll centrifugation are efficient
      techniques for the accumulation of spermatozoa with intact acrosomes. Because of
      the higher sperm recovery rate, glass wool filtration appears to be the more
      appropriate method.

PMID- 8559431
TI  - [Therapeutic management of recurrent uterine cervix carcinoma following surgery
      alone or surgery with complementary endocavitary curietherapy].
AB  - Sixty-eight cases of recurrence of cancer of the uterine neck, among which 8
      after conization and 60 after Wertheim's enlarged hysterectomy, in a group of 472
      patients are examined. No one of these 472 patients was subjected to external
      radiotherapy, because metastatic lymph nodes were not found at the time of the
      surgery of the primary tumor. The aim of the work was to examine the
      possibilities of identifying a subgroup of patients, among those without
      metastatic lymph nodes, for whom external radiotherapy, besides brachytherapy,
      could be considered useful on the basis of the extent of the primary tumor and of
      the histological type. Surgery has cured 11 patients; radiotherapy and
      radiochemotherapy possibly combined with surgery have cured 8 patients.
      Histological type and the extension of the tumor do not seem to influence the
      incidence of the relapses, however the authors opine that a multifactorial
      analysis, with includes other factors (HB rate, angiogenesis aneuploidism) could
      indicate a subgroup of patients for whom, in spite of absence of metastatic lymph
      nodes, could be concluded that the external precautional radiotherapy is useful.

PMID- 8559432
TI  - [The role of prostaglandin E2 in cervix maturation and labor induction. Clinical
      experience].
AB  - In obstetrics there are sometimes situations that require a prompt induction of
      labour. The possibility of employing prostaglandins instead of oxytocin would
      seem to increase the prospects of success. The aim of the present study is to
      strike a preliminary balance of our experience on how the use of exogenous PGE2
      (dinoprostone) helps to start the labour in term pregnant women. The study
      considered retrospectively a sample of 40 women that underwent one or more
      attempts to induct labour through intracervical application of PGE2 gel during
      the period 01/12/1992-01/04/1994. The results of the attempts were evaluated
      according to numerous parameters. In addition, we tried to define the prognostic
      value that could be attached to the characteristics of the tocogram an hour after
      dinoprostone had been administered. The percentage of success (88.89%) was high,
      while the incidence of instrumental deliveries and/or complications proved
      unimportant. The results of the attempts were positively linked to the Bishop
      score and to the regularity of the uterine contractions an hour after the
      application of PGE2. The utilization of dinoprostone proved effective and free
      from risks, authorising its clinical employment and the experimentation of new
      protocols.

PMID- 8559433
TI  - [Labor and delivery in a pregnancy involving fetal macrosomia].
AB  - The alleged connection between fetal magalosomia and the increased risk of
      maternal and perinatal morbidity justifies the lively discussion that has
      developed about the management problems caused by a big unborn child. The aim of
      this study is to offer a contribution to the definition of the more or less
      peculiar problems associated with labour and delivery in a pregnant women with a
      megalosomic fetus. The study was retrospectively carried out on a sample of 45
      women who, during the period 1190-1993, delivered a fetus weighing at least 4 kg.
      This sample was statistically compared with a numerically identical standard
      sample, selected at random. The main characteristics of labour and delivery were
      examined in the two groups under study. The most considerable differences
      observed concern the length of the labour, greater in the sample than in the
      standard group, and the frequency of dystocic events, similarly more considerable
      in the pregnant women with a megalosomic fetus. Maternal and perinatal outcomes,
      in spite of the small number of cesarean sections performed, were anyway very
      good in both the examined groups. In our experience, the risks associated with
      fetal megalosomia were rather limited, but this is not a reason to minimize
      beyond measure the problem we are talking about.

PMID- 8559434
TI  - [Frequency and mode of use of testing for HIV infection in women hospitalized for
      childbirth].
AB  - OBJECTIVE: To assess the use of HIV testing "because of pregnancy". DESIGN: Cross
      sectional study. PATIENTS: Parturients admitted to the obstetric divisions of a
      public hospital located in Rome (February-April 1994). INTERVENTION: Standardized
      interview during post test counseling. OUT-COMES: Frequency and characteristics
      of HIV testing "because of pregnancy" and women's know ledge on HIV sexual and
      vertical transmission. RESULTS: Among the 506 women admitted all consented to be
      tested and 3 were found HIV seropositive (0.6%). A total of 239 (47%) unselected
      parturients were interviewed; the remaining differ only for a lower rate of
      cesarean delivery (13% vs 54%). Of the interviewed, 140 (58%) had been already
      tested for HIV infection, 91 (38%) during the current pregnancy according to
      gynaecologist's prescription (79.87%) and without counseling (55.60%) or
      ascertained risk factors (82.90%); 40% had been tested after the first trimester
      of pregnancy. Rate of vertical transmission was estimated higher than 50% in 147
      cases; 150 women knew the "window period" but less than half estimated it
      correctly. CONCLUSIONS: The study showed a unsatisfactory use of HIV testing
      "because of pregnancy" and suggests the need for implementing in Italy
      information campaigns targeted both to women and gynecologists.

PMID- 8559435
TI  - [Role of radiotherapy in the combined treatment of invasive cancer of the vulva].
AB  - The authors review the literature on the different combinations of radiotherapy
      with chemotherapy and surgery with the aim of giving a state of art on the role
      of combined multimodality treatment of invasive vulvar carcinoma. From the data
      of the recent literature it appears that radiation integrated with surgery and
      chemotherapy can play an important role in reducing the risk of postoperative
      locoregional failure in patients with advanced primary or nodal disease and
      avoiding exenteration in patients with disease involving the anus or proximal
      urethra. This integrated multimodality therapy is a promising approach in the
      treatment of invasive vulvar carcinoma but further exploration in a larger number
      of patients is needed before giving consolidated data applicable in routine
      oncological clinical practice.

PMID- 8559436
TI  - [Prenatal diagnosis of pulmonary cystic dysplasia associated with a polymorphic
      variant of chromosome 19. A clinical case].
AB  - A case of congenital cystic adenomatoid malformation of the lung diagnosed during
      pregnancy with, echography in a foetus 19.4 weeks old is reported. The ACP is to
      be included among the most rare malformations, but even rarer is the prenatal
      diagnosis. It must to be noted that the previous child of the same couple was
      also found to be affected by a malformation of the lungs. Through a genetic study
      of the family it was discovered that both children and the father were carriers
      of the same morphological chromosomic variation. The authors report the case.

PMID- 8559437
TI  - [Effect of GnRH analogues on bone density in the vertebral column and the femur].
AB  - The objective of this study was to evaluate the effect on vertebral and femural
      bone density of the gonadotropin-releasing hormone (GnRH) analog administration.
      The changes in mineral bone density after 6 months discontinuation of the GnRH
      analog treatment were also measured. Forty-three premenopausal women with regular
      cycles and suffering from uterine myomatosis have been selected for the study.
      Twenty-eight women (group A) were treated with Goserelin 3.2 mg given as a depot
      every 28 days for 6 months. Fifteen women were treated with 10 mg of
      medroxyprogesterone acetate (MPA) from day 16 to day 25 of each month for 6
      months. Vertebral and femural bone density was measured (by Hologic QDR-X 1000)
      just before the start of the study, at 6 months of treatment and at 12 months
      (after 6 months of discontinuation treatment). Significant loss of vertebral bone
      density was demonstrated in women treated with GnRH analog. After six months of
      treatment discontinuation bone mineral density did not recover the pretreatment
      values. Bone femural density showed a not significant decrease in the GnRH analog
      group. In our experience, the treatment with GnRH analog in premenopausal women
      induces a reduction in lumbar bone density that is not reversible after the
      treatment withdrawal; for this reason it would be safe to add at the GnRH analog
      a therapy which can prevent the bone loss.

PMID- 8559438
TI  - [Use of a GnRH analogue in the treatment of certain forms of endometrial
      hyperplasia associated with menometrorrhagia].
AB  - Hyperestrogenism is a powerful factor inducing the development of endometrial
      hyperplasia that in its turn may represent the first step in the natural history
      of endometrial carcinoma. During menopause it is possible to have a condition to
      relative hyperestrogenism induced by a residual hormonal activity and by
      aromatisation of androgens in the adipose tissue. Therapeutical approach in this
      pathology aims to control hyperplastic development of the endometrial mucosa and
      to exclude menometrorrhagia. This study has been performed according to an open
      uncontrolled design in 14 women (4 menopausal women) with abnormal uterine
      bleeding and hysteroscopic endometrial cystic or adenomatous hyperplasia. At the
      beginning and at the end of treatment all patients underwent routine biohumoral
      blood-tests, hysteroscopy and diagnostic curretage. The GnRH analogue
      (tryptorelin) 3.75 mg 1 ampoule i.m. every 28 days was administered during a 6
      month treatment cycle. At the end of therapy bleeding had disappeared in all
      menopausal women; in the premenopausal group 8 patients have shown a normal
      menstrual cycle while 2 are still amenorrhoic. The final hysteroscopic evaluation
      displayed atrophic endometrium in 9 patients and simple proliferative endometrium
      in 5 cases. Safety was excellent: 3 cases of slight increase of systolic blood
      pressure and 1 case of slight increase of weight took place. Our results
      demonstrate therapeutic efficacy of GnRH analogues in the treatment of
      endometrial hyperplasia with menometrorrhagia either in premenopausal or
      menopausal women.

PMID- 8559439
TI  - [The diagnostic capacities of transvaginal echography and hysteroscopy in the
      characterization of endometrial pathology].
AB  - The diagnostic accuracy of transvaginal sonography (TVS) and hysteroscopy in the
      assessment of endometrial pathology was studied comparing retrospectively both
      methods with the results of histologic findings after dilatation and curettage
      (D&C) performed in the last four years on 467 patients, 155 of whom were in
      postmenopause. Endometrial thickness, tissue texture, myometrial invasion and
      haemodynamic characteristics were studied with TVS. Uterine cavity, endometrial
      patterns and superficial vascularization were evaluated by hysteroscopy. For the
      purpose of this study all histologic findings were subdivided to a) normal (206
      cases); b) benign lesions (240 cases); c) atypical hyperplasia or adenocarcinoma
      (21 cases). In our experience hysteroscopy was superior to TVS in detecting
      endometrial pathology. Both techniques were more sensitive in detecting
      premalignant and malignant lesions. Considering endometrial thickness evaluated
      with TVS as a single parameter in patients in postmenopause, we found that the
      most sensitive cut-off for defining normality was 3 mm; nevertheless, in the
      group of patients that had an endometrial thickness equal to or less than 3 mm
      there were 2 cases of malignancy. Therefore, neither TVS nor hysteroscopy are
      sufficiently reliable to replace curettage in the diagnosis of endometrial
      pathology.

PMID- 8559440
TI  - [The value of the Pap test in the diagnostic approach to HPV infection of the
      cervix uteri].
AB  - HPV infection of the low genital tract is the most diffuse STD world wide. For
      this reason it's necessary to follow a simple flow chart to reach a correct
      diagnosis and to practice an adequate therapy. The authors relate on their
      experience in the management of a group of patients they have observed in a STD
      clinic. In this group it was executed a diagnostic protocol including Pap test,
      in situ hybridization, dot blot and histologic examination on tissue biopsies.
      From the analysis of the obtained data, the authors state that the Pap test is
      very useful to start in the diagnostic protocol, for it is precise, inexpensive
      and allows to identify the patients to follow with further diagnostic procedures
      such as colposcopy and histologic examination, in order to reach an exhaustive
      diagnosis and to assess the proper therapy.

PMID- 8559441
TI  - [Fetal lesions due to the bistoury during cesarean section: a study of 58 cases.
      The 5-year case records of 3117 cesarean sections at the Institutes of Clinical
      Obstetrics and Gynecology of the University of Rome La Sapienza].
AB  - In the present article the authors have carried out a statistical investigation
      on data relative to the caesarean sections performed in the Departments of
      Obstetrics and Gynaecology of the University of Rome "La Sapienza" since 1986 to
      1990. Particular object of this study is to evaluate data regarding fetal
      bistoury lesions incidentally caused while performing the incision of the uterine
      wall during a caesarean section. To our knowledge, this topic has never been
      taken into account by the world's literature, nevertheless it is important also
      for its legal and insurance implications. Throughout the mentioned period 13787
      deliveries occurred, 3117 of which were caesarean sections: this is equal to a
      frequency of 22.6%, with an increase rate of 37.5% during the whole 5 years time.
      58 cases of fetal bistoury lesions have been found to occur since 1986 to 1990:
      this equal to 1.8% of all the performed caesarean sections. Even if their gravity
      was usually scarce, and only 7 cases needed a specific treatment, 25.8% of these
      lesions involved areas such as forehead, cheek bone, cheek, mostly related to
      possible aesthetic damages with their connected legal consequences. In order to
      evaluate what factors can contribute to the occurrence of these lesions and
      taking account of the large number of factors that may be involved (such as
      conditions at which the operation is performed, skill and experience of the
      surgeon etc.), the authors focus their attention to those which, for their
      clinical significance and possibility of detection, suit more than others such a
      statistical investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559442
TI  - [The biochemical screening of Down's syndrome].
AB  - Since the initial observation of an association between low maternal serum aFP
      and trisomies noninvasive for chromosomal abnormalities is an obvious goal of
      genetics and obstetricians. Here are reported the results of a biochemical
      screening for fetal trisomies study based on the dosages of maternal serum aFP,
      bHCG and uE3 at 16 week gestational age on 1166 pregnant women without risk
      factors for genetical abnormalities. Sensitivity, positive predictivity and
      negative predictivity of the screening were 50%, 42.86% and 99.74% respectively.

PMID- 8559443
TI  - [The emotive and cognitive reactions in temporary pharmacological menopause].
AB  - The authors have attempted to evaluate the extent to which menopausal crisis is
      linked to hypoestrogenism and the extent to which it is linked to the
      socioenvironmental context in which it takes place. The study analyses emotional
      and cognitive aspects in a group of women in temporary menopause which was
      pharmacologically induced for therapeutic purposes. The study was carried out in
      30 patients suffering from benign gynecological pathologies receiving ovarian
      steroidogenesis-blocking treatment. Treatment consisted of a subcutaneous
      administration of a Gn-Rh analog every 28 days for 6 months. After having
      collected information regarding the symptoms that appeared following the
      administration of therapy, the authors evaluated the emotive (anxiety and
      depression) and cognitive (short-term memory and concentration) conditions of
      patients using psychometric reactives performed during the first check-up, and
      then repeated at the 3rd, 5th and 7th control visit: the State-Trait-Anxiety
      Inventory to assess trait anxiety and state anxiety; scale D of the Minnesota
      Multiphasic Personality Inventory to assess depression; the sub-test for memory
      of figures from Wechsler-Bellevue Intelligence Scale to evaluate short-term
      memory; the Toulouse-Pieron reactive to evaluate attention and concentration. The
      results obtained were analysed statistically using Student's t-test and Pearson's
      coefficient. An analysis of the data shows that, after the first doses of the
      drug stress trends to diminish from the high levels recorded at the first visit,
      stabilising at normal values throughout treatment. Like anxiety and depression,
      concentration and memory do not show marked variations.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8559444
TI  - [Dysspermia due to inflammation. The evaluation of sperm cultures].
AB  - The study evaluates 160 cases of positive spermioculture taken from 522 sterile
      individuals examined by the authors at the Couple Sterility Outpatient unit in
      Department A of the Institute of Gynecology and Obstetrics at Turin University
      during the period between January 1984 and December 1993. The germs responsible
      for infection were assayed in order to evaluate the strains which showed the
      highest incidence every year. Whereas there was no significant change in the
      absolute number of cases of sterility over the period, the number of cases caused
      by infection increased significantly during the second five-year period. It was
      found that the germs predominantly implicated in the genesis of male sterility
      formed part of the so-called mixed flora group, responsible in women for
      syndromes of often asymptomatic bacterial vaginosis which are not identified and
      consequently not treated.

PMID- 8559445
TI  - [Blue nevus of the endocervix].
AB  - We report a case of blue nevus of the uterine cervix discovered in a cone removed
      for other reasons. The lesion can be interpreted as a visceral analogue of the
      cutaneous blue nevus. Histological and Immunohistological studies suggest the
      melanocytic nature of the lesion.

PMID- 8559446
TI  - [Piperacillin in prevention and therapy in gynecological surgery].
AB  - The authors have studied the use of sodic piperacillin in surgical gynecological
      prophylaxis. The drug, used in the intravenous tract, has proved efficacious for
      broad spectrum of antibacterial action versus gram+, gram-, and anaerobic and
      aerobic. It has shown an excellent tolerability by reducing hospital surgical
      infections (11% of cases) and sepsis (9.2% of cases) with social, economic and
      professional advantages.

PMID- 8559447
TI  - [The possibility of using sulprostone during laparoscopic myomectomy in uterine
      fibromyomatosis. Preliminary studies].
AB  - The authors considered sulprostone effects, PGE2 synthetic derivative, on the
      hematic loss during laparomyomectomy. This drug is been used by intravenous way
      during the operation in 84 patients affected with uterine myomatosis. The
      effectiveness and tolerance of the drug is thus evident in the reduction of the
      hematic intraoperative loss.

PMID- 8559448
TI  - von Hippel-Lindau syndrome: a rare syndrome as the clue for the molecular basis
      of common renal disorders.

PMID- 8559449
TI  - Look who's talking--intracellular communication in chronic vascular disease.

PMID- 8559450
TI  - Molecular mechanisms in renal phosphate reabsorption.

PMID- 8559451
TI  - The fibroblast--a (trans-) differentiated cell?

PMID- 8559453
TI  - A renocentric view of essential hypertension: lessons to be learnt from kidney
      transplantation.

PMID- 8559452
TI  - 11 beta-hydroxysteroid dehydrogenase--why is it important for the nephrologist?

PMID- 8559454
TI  - Effect of low-protein diets on renal disease: are non-haemodynamic factors
      involved?

PMID- 8559455
TI  - The patient with type II diabetes and uraemia--to transplant or not to
      transplant.

PMID- 8559456
TI  - Pharmacokinetics and drug dosage adjustment to renal impairment.

PMID- 8559457
TI  - Renin and hypertension.

PMID- 8559458
TI  - Salt and hypertension: where things stand.

PMID- 8559459
TI  - Novel aspects of renal fibrogenesis.

PMID- 8559460
TI  - Molecular mechanisms of lymphocyte activation.

PMID- 8559461
TI  - Liver and kidney in acid-base regulation.

PMID- 8559462
TI  - Acid-base and potassium homeostasis.

PMID- 8559463
TI  - Tubular function and acid-base disturbances.

PMID- 8559464
TI  - Is it necessary to treat metabolic acidosis in chronic renal insufficiency?

PMID- 8559465
TI  - Renal tubular dysfunction and acidosis.

PMID- 8559466
TI  - Sodium channels and non-selective cation channels in the cortical collecting
      duct.

PMID- 8559467
TI  - Physiology of cell survival and cell death: implications for organ conservation.

PMID- 8559468
TI  - How T cells recognize alloantigen: evidence for two pathways of allorecognition.
AB  - During allograft rejection, both allorecognition pathways seem to be effective.
      The direct pathway, where T-cell receptors directly recognize intact allo-MHC
      with or without bound peptides on the surface of target cells, accounts for most
      of the cytotoxic T cell function. The indirect pathway in contrast, where T-cell
      receptors recognize MHC allopeptides after processing and presentation by self
      APCs, may lead to the activation of T helper cells which secrete cytokines and
      provide the necessary signals for the growth and maturation of effector cytotoxic
      T lymphocytes and B cells leading to allograft rejection. The role of the
      indirect pathway is supported by the findings that mouse skin transplants from a
      class II deficient donor can be rejected involving CD4+ self-restricted T-cell
      recognition of donor antigen. In addition, rats primed by class I MHC peptides do
      reject skin grafts as well as renal allografts in an accelerated fashion. Studies
      showing that synthetic class II peptides can also be used to tolerize animals for
      a subsequent renal transplant further underline the importance of this self
      restricted recognition of allo-MHC. More studies are needed to better define the
      contribution of this self-restricted T cell recognition of processed allo-MHC to
      the rejection process in particular in regard to its suggested role in chronic
      allograft failure as well as to its susceptibility to therapeutic regimens in
      organ transplant recipients.

PMID- 8559469
TI  - Control of renal microcirculation.

PMID- 8559470
TI  - Intrarenal renin-angiotensin system and its contribution to the regulation of
      glomerular haemodynamics.

PMID- 8559471
TI  - Effector mechanisms in renal allograft rejection.

PMID- 8559472
TI  - Biology of erythropoietin production.

PMID- 8559473
TI  - Progression of renal failure: what is the role of cytokines?

PMID- 8559474
TI  - Are corticosteroids really necessary in renal transplantation?

PMID- 8559475
TI  - TGF-beta upregulates interleukin 6 production by rat glomerular epithelial cells
      in vitro.
AB  - BACKGROUND: Glomerular epithelial cells (GECs) play an important role in
      maintaining normal glomerular permselectivity in vivo. Recent in-vitro studies
      have suggested that GECs are able to secrete substances which may modulate
      glomerular injury. Interleukin 6 (IL-6) has been shown to be a potent mediator of
      glomerular injury. It is also known that IL-6 could be produced by various cells.
      METHODS: IL-6 production by rat GECs in culture was examined in this study. IL-6
      bioactivity in conditioned medium collected from cultured GECs (GEC-CM) was
      measured using IL-6 dependent murine hybridoma cell line, namely B9 cells. IL-6
      gene expression by GECs was analysed by reverse transcriptase polymerase chain
      reaction (RT-PCR). Effects of recombinant IL-6 on the proliferation of GECs and
      type IV collagen secretion by GECs were evaluated to examine the possible role of
      GECs derived IL-6. RESULTS: GEC-CM stimulated B9 cells growth in a dose dependent
      fashion. The mitogenic activity was inhibitable by anti-murine IL-6 antibody. De
      novo synthesis of IL-6 was suggested by the demonstration of IL-6 mRNA by GECs
      using the RT-PCR. Secretion of IL-6 by GECs was increased by transforming growth
      factor beta but not by IL-1 beta. Recombinant murine IL-6 stimulated GECs growth
      and their type IV collagen secretion. CONCLUSIONS: These results indicate that
      rat GECs could produce IL-6 which may modulate glomerular inflammation and that
      IL-6 may function as an autocrine factor for GECs.

PMID- 8559477
TI  - Anticipation of age at renal death in autosomal dominant polycystic kidney
      disease (ADPKD)?
AB  - It has been claimed that anticipation occurs in ADPKD, i.e. endstage renal
      failure at progressively earlier age in successive generations. This observation
      might possibly point to unstable DNA as the molecular basis of ADPKD. We analysed
      74 parent-offspring pairs of 148 families in Germany and Austria in whom (i)
      ADPKD was verified by appropriate imaging procedures and (ii) age at renal death
      was accurately known. The median difference for age at renal death between parent
      and offspring was 0 years, range -26.3 to +27.2 years. There was no deviation
      from normal (Gaussian) distribution according to the Shapiro-Wilk test (P =
      0.75). We conclude that systematic anticipation cannot be demonstrated with this
      sample which had sufficient size for meaningful biostatistical analysis.

PMID- 8559476
TI  - Effect of diltiazem and methyldopa on gestation-related renal complications in
      rats with adriamycin nephrosis. Relationship to glomerular prostanoid synthesis.
AB  - BACKGROUND: In the presence of pre-existing renal disease, occurrence of
      hypertension during pregnancy may compromise renal function and aggravate
      proteinuria. In pregnant rats with early adriamycin nephropathy, this is
      associated with an increase in the glomerular TxB2:PGE2 ratio. In the present
      study we evaluated the effect of blood-pressure control on renal function and its
      relationship with glomerular prostanoid synthesis. DESIGN OF THE STUDY: Pregnant
      Wistar rats with adriamycin nephropathy received diltiazem, 30 mg/kg/day or
      methyldopa, 400 mg/kg/day from mid-gestation. Mean arterial pressure (MAP),
      inulin clearance (CIN), urine protein excretion (UP) and glomerular prostanoid
      synthesis were measured. Results were compared with (i) untreated pregnant rats
      with adriamycin nephropathy, (ii) virgin rats with adriamycin nephropathy, and
      (iii) normal virgin or (iv) pregnant normal rats. RESULTS: MAP increased in
      untreated pregnant rats with adriamycin nephropathy (P < 0.01 versus virgin rats
      with adriamycin nephropathy), contrasting with the physiological decrease
      observed in normal pregnant rats. Diltiazem and methyldopa decreased MAP to
      normal values. In untreated pregnant rats with adriamycin nephropathy CIN
      decreased and proteinuria increased significantly at the end of gestation.
      Treatment with diltiazem and methyldopa augmented GFR, but only diltiazem
      decreased UP significantly. It was associated with an increased glomerular PGE2
      synthesis. CONCLUSION: We conclude that in rats with adriamycin nephropathy,
      antihypertensive treatment improved GFR. Diltiazem also decreased urinary protein
      excretion, associated with a normalization of the glomerular TxB2:PGE2 ratio.

PMID- 8559478
TI  - Chronic hypokalaemia of adults: Gitelman's syndrome is frequent but classical
      Bartter's syndrome is rare.
AB  - We evaluated 27 adult patients with chronic hypokalaemia (K+ = 2.9 +/- 0.2
      mmol/l), documented over at least 5 years, in whom the cause of the hypokalaemia
      had not been clarified in spite of previous testing. In 15 patients it was
      possible to establish a diagnosis by a thorough outpatient workup (diuretic abuse
      (n = 5), surreptitious vomiting (n = 8), laxative abuse (n = 1), renal tubular
      acidosis (n = 1)). Commonly utilized tests such as measurements of plasma renin
      activity, plasma aldosterone, and urinary potassium concentration proved not to
      be useful in the differential diagnosis of these patients. In contrast the
      following were diagnostically important: in surreptitious vomiting the
      hypochloraemia, the mild renal insufficiency, and the extremely low urinary
      chloride concentration; in diuretic abuse the high urinary concentration of
      chloride together with repeatedly positive toxicology screens for diuretics; in
      laxative abuse the high stool weight and extremely low urinary sodium
      concentration. In the remaining 12 patients none of these diagnoses applied and
      further tests for suspected Bartter's syndrome were done in the
      hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559479
TI  - Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal
      calcium stone formers and healthy controls.
AB  - The calciuric response after an oral calcium load (1000 mg elemental calcium
      together with a standard breakfast) was studied in 13 healthy male controls and
      21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa
      x V > 7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2
      vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6 +/-
      5.1 versus 50.9 +/- 5.0 pg/ml), whereas it tended to increase in hypercalciuric
      (from 53.6 +/- 3.2 to 60.6 +/- 5.4 pg/ml, P = 0.182) and fell in normocalciuric
      stone formers (from 45.9 +/- 2.6 to 38.1 +/- 3.3 pg/ml, P = 0.011). The total
      amount of urinary calcium excreted after OCL was 2.50 +/- 0.20 mmol in controls,
      2.27 +/- 0.27 mmol in normocalciuric and 3.62 +/- 0.32 mmol in hypercalciuric
      stone formers (P = 0.005 versus controls and normocalciuric stone formers
      respectively); it positively correlated with serum calcitriol 6 h after calcium
      load (r = 0.392, P = 0.024). Maximum increase in urinary calcium excretion rate,
      delta Ca-Emax, was inversely related to intact PTH levels in the first 4 h after
      calcium load, i.e. more pronounced PTH suppression predicted a steeper increase
      in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate
      was inversely related to the ratio of delta calcitriol/deltaPTHmax after calcium
      load (r = -0.653, P = 0.0001), indicating that an abnormally up-regulated
      synthesis of calcitriol and consecutive relative PTH suppression induce
      hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559480
TI  - High-risk features of lupus nephritis: importance of race and clinical and
      histological factors in 166 patients.
AB  - BACKGROUND: The pleomorphic nature of lupus nephritis has confounded efforts to
      refine estimates of prognosis. Consideration of interactions among prognostic
      factors may help to identify high-risk patients. METHODS: By univariate and
      multivariate survival analysis, race and attributes of severe active lupus
      nephritis were evaluated as potentially important prognostic factors in 166
      patients upon entry into prospective therapeutic trials of lupus kidney disease.
      RESULTS: Black patients were significantly more likely than others to develop
      renal insufficiency. Cellular crescents emerged as the most predictive active
      pathological feature and interstitial fibrosis was the strongest chronic
      histological prognostic factor. Combinations of these morphological attributes
      identified particularly high-risk individuals. Patients with 50% or more cellular
      crescents and those with less extensive cellular crescents plus moderate to
      severe interstitial fibrosis were at markedly increased risk for doubling serum
      creatinine compared to those who lacked these histologic features (P < 0.0001).
      Azotaemia, anaemia, hypocomplementaemia, hypertension, tubular atrophy and
      glomerular sclerosis were also associated with an increased probability of renal
      function deterioration. Serum creatinine, haematocrit, race, and kidney pathology
      data emerged as independent predictors of renal insufficiency. Black patients in
      this study were more likely than the others to have high-risk histological
      features, including extensive cellular crescents (> or = 50%) and moderate to
      severe interstitial fibrosis, prior to randomization. CONCLUSIONS: Combinations
      of high-risk demographic, clinical and histological attributes identify patients
      at increased risk for progressive renal function deterioration. Several factors,
      including the severity of kidney biopsy findings, probably contribute to the poor
      prognosis of Black patients in this study population.

PMID- 8559481
TI  - Sequential analysis of variation in glomerular filtration rate to calculate the
      haemodynamic response to a meat meal.
AB  - BACKGROUND: The renal haemodynamic response to a meat meal is usually measured as
      either filtration capacity (maximal achieved GFR), or renal reserve (maximal GFR
      increase over baseline), or percent renal reserve (maximal GFR increase as a
      percentage of baseline). The time-course of GFR response to a meat meal varies in
      different individuals as the peak GFR tends to occur late in renal disease. This
      study proposes a new method to measure the GFR response independently of
      differences in peaking time. METHODS: The study is based on measurement of GFR
      (inulin clearance, ml/min x 1.73 m2 BSA) in three 30-min pre-meal clearance
      periods (baseline) followed by analysis of the GFR changes for up to 180 min
      (four 30-min and one 60-min clearance periods) after a meat meal (2 g of
      protein/kg of BW as red cooked meat). Data were analysed from 85 healthy people
      (GFR > or = 100) and 273 individuals with renal disease (RD) who were divided
      into three groups based on their baseline GFR (RD1, n = 115, GFR 99-66; RD2, n =
      85, GFR 65-33; RD3, n = 73, GFR < 33). RESULTS: In healthy people after the meat
      meal GFR peaked between 30 and 60 min and returned to baseline by 120 min. In the
      three RD groups GFR peaked later than in healthy people (P < 0.001) and remained
      higher than baseline for up to 180 min (P < 0.001). Cumulative post-meal GFR
      changes, calculated as cumulative GFR increase over baseline up to 120 min after
      meal (ml/120 min x 1.73 m2 BSA), were significantly different (P < 0.01) in the
      four groups (healthy people, 937 +/- 141; RD1, 1222 +/- 141; RD2, 587 +/- 104;
      RD3, 361 +/- 89). Interindividual variability in cumulative GFR increase was only
      partially explained by the value of filtration capacity (r2 = 0.285), renal
      reserve (r2 = 0.640), and percent renal reserve (r2 = 0.175). CONCLUSION: The
      data indicate that commonly used parameters are poor indices of the actual total
      time-course of the renal response to a protein load.

PMID- 8559483
TI  - Age as a determinant of glomerular filtration rate in non-insulin-dependent
      diabetes mellitus.
AB  - BACKGROUND: The level of glomerular filtration rate (GFR) and its determinants in
      non-insulin-dependent diabetes mellitus (NIDDM) are currently controversial.
      DESIGN OF THE STUDY: We measured GFR and effective renal plasma flow (ERPF) in
      121 consecutive NIDDM without evidence of overt diabetic nephropathy. Age varied
      from 28 to 70 years, 61.2% were women and known duration of NIDDM was 0-37 years.
      Hypertension was detected in 36.4% of patients and 47.8% had microalbuminuria.
      RESULTS: An inverse correlation was found between GFR and age, but not with known
      duration of NIDDM: It was a weak correlation (r = -0.41) but statistically
      significant (P < 0.001). The other variables considered were not significant by
      multiple stepwise regression analysis, but patients with lower GFR tended to have
      diabetic retinopathy more frequently. GFR was lower in hypertensive compared to
      normotensive patients (123 +/- 28.4 versus 136 +/- 32.5 ml/min/1.73 m2; P <
      0.05), but was not different between patients with normal and elevated albumin
      excretion rate. ERPF also had an inverse correlation with age (r = -0.45, P <
      0.001). CONCLUSION: We conclude that (i) age should be considered as a
      confounding variable when evaluating GFR in patients with NIDDM, and (ii) the age
      dependent decline in GFR may mask hyperfiltration in the early stages of diabetic
      nephropathy in NIDDM:

PMID- 8559482
TI  - Heterogeneity of renal carcinoma.
AB  - Monoclonal antibodies were used to study the expression of three recently
      characterized basement membrane components and two carbohydrate antigens in 11
      renal-cell carcinomas, using immunohistological and biochemical techniques. The
      expression of several site-specific kidney antigens in renal-cell carcinoma were
      studied to determine the origin of the carcinoma and if it is possible further
      classify this type of carcinoma. Tubulointerstitial nephritis antigen (TIN) and
      two alpha-chains of type IV collagen, alpha 1 (IV) and alpha 3 (IV) were studied.
      In addition the expression of carbohydrate antigens Lex and SLex, which also
      exhibit site-specific distribution were characterized. Lex and SLex antibodies
      stained the majority of the tumours. TIN was expressed in 9 of 11 tumours, the
      alpha 1 (IV) chain was present in all 11, and the alpha 3 (IV) chain in two of
      the 11 tumours. Interestingly, the two alpha 3 (IV)-positive tumours were the
      same two that were negative for TIN. In normal tissue alpha 3 (IV) is found in
      distal tubules while TIN is found in proximal tubules. Our results are consistent
      with earlier observations that the proximal tubule is the origin of most renal
      cell carcinomas, but the results also indicate that renal-cell carcinoma may
      originate from the distal tubule.

PMID- 8559484
TI  - Elevated body lead burden from drinking water in end-stage chronic renal failure.
AB  - Delta aminolaevulinic acid dehydratase (ALA-D) who assayed in 66 patients with
      end-stage renal failure who live in a region where there is a high risk of lead
      poisoning from drinking water (Vosges mountains). Sixty patients received
      dialysis and six underwent renal transplantation. Results were compared to those
      obtained in 366 control subjects with normal renal function hospitalized in a
      department of Internal Medicine and living in the same geographical area. The ALA
      D level was significantly lower in dialysed patients (0.40 +/- 20) than in
      controls (0.57 +/- 0.31) (P = 0.0014). Transplant recipients had ALA-D levels
      comparable to subjects with normal renal function (0.59 +/- 0.37). In this high
      risk population an EDTA test was performed in 74 subjects (with normal renal
      function and 17 dialysis patients in combination with haemofiltration for the
      latter patients. In the two study groups a negative correlation was found between
      ALA-D and the amount of lead chelated during the 24 h following administration of
      EDTA (r = -0.77 and -0.88 respectively). In subjects who live in an area of
      endemic lead poisoning, the incidence of elevated body lead burden from drinking
      water was similar in the group with normal renal function and in the group of
      dialysed patients (18.6 and 8.3% respectively). This study shows (i) that in
      dialysis patients, measurement of ALA-D represents an accurate screening test for
      lead overload, provided that the lower threshold of normal is lowered from 0.40
      to 0.20, and (ii) that diagnosis and treatment are possible by administering EDTA
      in conjunction with haemofiltration or CAPD.

PMID- 8559485
TI  - Effects of selenium supplementation on immune parameters in chronic uraemic
      patients on haemodialysis.
AB  - BACKGROUND: The involvement of selenium (Se) in immune response has been
      increasingly recognized, cell-mediated immunity being principally affected by Se
      deficiency. Blood Se levels in chronic uraemic patients are frequently lower than
      in controls, and in these patients cellular immunity in generally impaired.
      METHODS: The present study was designed to assess the effects of Se
      supplementation over 6 consecutive months on immune parameters in haemodialysis
      (HD) patients from Rostock (Germany) and Chieti (Italy). In both cities, five
      patients were supplemented with Se (500 micrograms thrice weekly for 3 months,
      then 200 micrograms thrice weekly for the next 3 months), whereas another five
      patients received placebo. All Se determinations were performed in a single
      laboratory. RESULTS: In both cities, basic plasma Se levels were significantly
      lower in patients than in their corresponding normal controls. After beginning Se
      supplementation, plasma Se concentration promptly normalized and levelled off in
      the normal range throughout the study. Se administration was well tolerated by
      all patients, and no side-effects attributable to Se toxicity were observed.
      Although no major change in immunocompetent cells (white blood count, total
      lymphocyte count, lymphocyte subpopulations) was observed during Se therapy, an
      improvement in T-cell response to phytohaemoagglutinin (as evaluated in Rostock
      patients) and a significant progressive increase in delayed-type hypersensitivity
      (as evaluated in Chieti patients) was observed in supplemented patients. After 6
      months of Se therapy, the increase in delayed-type hypersensitivity of
      supplemented patients proved to be significantly higher when compared to both
      presupplementation values and to the results found in non-supplemented patients.
      Three months after suspension of Se supplementation, plasma Se levels and delayed
      hypersensitivity significantly decreased in Chieti patients, with both parameters
      returning similar to presupplementation values. CONCLUSIONS: In accordance with
      previous studies done in non-uraemic subjects, our investigation demonstrates for
      the first time the immunostimulatory properties of Se in HD patients. Though
      several problems on Se metabolism in uraemia remain unresolved, in our opinion
      moderate and safe Se supplementation can be beneficial in chronic uraemic
      patients.

PMID- 8559486
TI  - Expression of receptors for advanced glycosylated end-products in renal disease.
AB  - BACKGROUND: Advanced glycation endproducts (AGEs) are believed to mediate long
      term complications in diabetes mellitus. In this context we studied the
      expression of the receptor for AGEs (RAGE) in the kidney of patients with a
      variety of different renal diseases. METHODS: RAGE was detected by
      immunocytochemistry in renal biopsies. We compared the staining for RAGE in nine
      patients with diabetic nephropathy, 20 with inflammatory and/or immune complex
      and 10 with non-inflammatory renal diseases. Normal renal tissue from seven
      patients with tumour nephrectomies served as controls. RESULTS: In controls the
      only cells expressing RAGE constitutively were interstitial cells and vascular
      smooth muscle cells (6/7), while distal tubular cells were rarely positive (1/7).
      Endothelial cells of arteries/arterioles, glomerular endothelial cells,
      podocytes, and capsular epithelial cells were consistently negative. In diabetic
      nephropathy, inflammatory and/or immune complex, and non-inflammatory renal
      diseases, all cell types mentioned above became positive for RAGE. Whilst the
      distribution of RAGE in the tissue was quite similar, staining intensity in
      inflammatory and/or immune complex diseases was higher than in diabetic
      nephropathy. CONCLUSION: RAGE induction in the kidney is not specific for
      diabetic nephropathy and occurs in other types of renal diseases as well.

PMID- 8559487
TI  - Atherogenic lipid profile and lipoprotein(a) in relation to serum albumin in
      haemodialysis patients.
AB  - Malnutrition in haemodialysis patients is associated with an increased
      cardiovascular mortality. Lipoprotein(a) (Lp(a)) is an independent risk factor
      for atherosclerotic cardiovascular disease. To evaluate the relationship between
      atherogenic lipid profile and serum albumin in haemodialysis patients we measured
      fasting serum Lp(a), total cholesterol (TC), high-density lipoprotein-cholesterol
      (HDL-C), triglyceride (TG), apoprotein A-I (ApoA-I), apoprotein B (ApoB) and
      albumin in 101 haemodialysis patients and in 46 healthy subjects as a control.
      The haemodialysis patients were divided into two groups on the basis of the level
      of serum albumin: group I, serum albumin < 4.0 g/dl; group II, serum albumin > or
      = 4.0 g/dl. Haemodialysis patients as a whole (n = 101, 17.1 mg/dl (10.3-30.9))
      had higher serum Lp(a) than normal subjects (n = 46, 10.5 mg/dl (3.3-24)) (P <
      0.05). Lp(a) in group I (n = 38, 27.1 mg/dl (14.6-35.0)) was significantly higher
      than in group II (n = 63, 14.5 mg/dl (7.7-21.7), P < 0.005) and normal subjects
      (P < 0.0005). However, serum Lp(a) level of group II was not different from those
      of normal subjects. There was a significant inverse correlation between serum
      Lp(a) and albumin concentration (rs = -0.26, P < 0.01). TC, TG, HDL-C, ApoA-I,
      ApoB, TC/HDL-C, and ApoA-I/ApoB ratios were not different between group I and
      group II. No correlation was found between albumin and TC, TG, HDL-C, TC/HDL-C,
      and ApoA-I/ApoB ratios. These results suggest that Lp(a) could be responsible for
      an increased cardiovascular mortality in haemodialysis patients with
      malnutrition.

PMID- 8559488
TI  - Highly sulphated glycosaminoglycans in articular cartilage and other tissues
      containing beta 2 microglobulin dialysis amyloid deposits.
AB  - BACKGROUND: Highly sulphated glycosaminoglycans (GAGs) are a common constituent
      of amyloid deposits and an integral component of articular connective tissues
      where beta 2-microglobulin (beta 2M) amyloid is most often found. METHODS: Using
      alcian blue, magnesium chloride, critical electrolyte concentration, mucin
      histochemistry, and immunohistochemistry, the GAGs composition of beta 2M amyloid
      deposits in joint capsule and cartilage, carpal, and heart tissues of 22 uraemic
      patients was determined. RESULTS: Highly sulphated GAGs were found in beta 2M
      amyloid deposits not only within cartilage, where such GAGs are normally found in
      high concentration, but also in other articular and extra-articular connective
      tissues. Keratan sulphate was often specifically localized to beta 2M amyloid
      deposits in articular cartilage and to a lesser extent in periarticular tissues,
      with one case showing colocalization with systemic vascular amyloid deposition.
      Other sulphated GAGs, chondroitin 4 and 6 sulphate, dermatan sulphate, and
      heparan sulphate were also identified in tissues containing beta 2M amyloid
      deposits, but with the exception of heparan sulphate (identified by mucin
      histochemistry) were not specifically localized to the deposits themselves.
      CONCLUSIONS: These findings suggest that qualitative or quantitative changes in
      the composition of highly sulphated GAGs may play a role in localization of beta
      2M amyloid deposits in articular and extra-articular tissues.

PMID- 8559489
TI  - Adherence of human monocytes to haemodialysis membranes: LFA 1 (CD11a/CD18) CR1
      (CD35) and CR3 (CD11b/CD18) triggering promotes the biosynthesis of platelet
      activating factor and adherence.
AB  - BACKGROUND: Platelet-activating factor is a mediator of inflammation involved in
      the blood-membrane interaction. We report that selective stimulation of
      complement receptors (CR1 and CR3) triggers PAF synthesis and monocyte adherence
      to complement-activating membranes. METHODS: The synthesis of PAF was studied
      after stimulation of normal human adherent monocytes with F(ab)2 and Fab
      fragments of monoclonal antibodies specific to CR1 and CR3. CD11a, CD11b, CD18,
      and CD35 was studied by flow cytometry on neutrophils and monocytes. The
      molecular species of PAF from stimulated monocytes were identified by reverse
      phase high-performance liquid chromatography coupled with mass spectrometry.
      RESULTS: Anti-CR1 and anti-CR3 monoclonal antibodies induced a dose-dependent C
      16 but not C-18 PAF production. The latter occurred also with monovalent Fab
      fragments of both anti-CR1 and anti-CR3 monoclonal antibodies, that were not
      internalized as seen by immunofluorescence. Adherence of monocytes to Cuprophan
      membranes was markedly higher (P < 0.01) in membranes pretreated with fresh than
      with heat-inactivated normal plasma. However, the high adherence to fresh plasma
      treated membranes was completely abrogated by coincubating the cells with Web
      2170, a specific PAF receptor antagonist. This was not due to downregulation of
      adhesion molecules expression on leukocytes. CONCLUSIONS: These studies implicate
      a crucial role of PAF in blood interaction with haemodialysis membranes that fix
      complement activated products.

PMID- 8559490
TI  - Kinin kinetics during different dialysis protocols with AN69 dialyser in ACEI
      treated patients.
AB  - The effect of different dialysis modes on kinin kinetics was studied in seven
      stable haemodialysis patients treated with AN69 dialysers and ACE inhibitors
      (ACEI). AN69 haemodiafiltration with calcium-enriched substitution (HDF), AN69
      haemodialysis with 1.75 (HD 1.75) and 1.50 (HD 1.50) mmol/l dialysate calcium,
      AN69 haemodialysis with 1.25 mmol/l dialysate calcium and substitution of 2.25
      mmol/h calcium (HD+Ca), and cellulose acetate haemodiafiltration (CA HDF) were
      compared. Dialysis was uneventful in all patients. During dialysis, serum
      calcium, sodium, pH, albumin, and bradykinin were measured at the start and after
      5 min at arterial, venous, and postinfusion side of the extracorporeal circuit.
      Serum predialysis bradykinin was 107 +/- 18fmol/ml (mean +/- SEM) in patients on
      HDF, 61 +/- 9 fmol/ml in patients on HD 1.50, 49 +/- 13 fmol/ml in patients on HD
      1.75, 35 +/- 3 fmol/l in patients on HD+Ca, and 75 +/- 27 fmol/ml in CA HDF. No
      significant change of mean bradykinin levels occurred after 5 min at the arterial
      and venous side of the dialyser or postinfusion. Individual high bradykinin
      levels, up to 2672 fmol/ml, were observed but without clinical consequences,
      suggesting that the threshold value is difficult to determine. No significant
      correlations were evidenced between bradykinin levels and any of the biochemical
      measurements. The present data show an intraindividual variability of the
      bradykinin levels with variation coefficients ranging from 0.386 to 2.783. The
      present study illustrates that haemodialysis and haemodiafiltration with AN69 in
      ACEI-treated patients, under the present conditions, does not result in
      anaphylactoid reactions or in a clinically significant release of
      bradykinin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559491
TI  - No generation of bradykinin with a new polyacrylonitrile membrane (SPAN) in
      haemodialysis patients treated with ACE inhibitors.
AB  - BACKGROUND: Anaphylactoid reactions occurring in uraemic patients haemodialysed
      with polyacrylonitrile haemodialysis (HD) membranes and being treated with ACE
      inhibitors have been attributed to an excessive generation of bradykinin.
      METHODS: Here we tested in a prospective trial a new type of polyacrylonitrile
      membrane (SPAN) with respect to bradykinin generation in nine HD patients
      receiving either captopril or enalapril. Each patient had three consecutive HD
      sessions with each of the three tested membranes, high-flux SPAN, high-flux
      polysulphone (F60) and low-flux Hemophan (GFS Plus 16). RESULTS: No clinical
      signs of anaphylactoid reactions were observed in any of these patients but the
      number of patients was relatively small and the duration of exposure to different
      membranes relatively short. At 5 min after the start of HD session, plasma
      bradykinin levels were significantly higher in the venous than in the arterial
      line for all three HD membranes: SPAN, 18.5 +/- 11.9 versus 12.4 +/- 5.3 fmol/ml
      (P < 0.05); F60, 19.0 +/- 13.8 versus 11.5 +/- 6.5 fmol/ml (P < 0.01); and GFS
      Plus 16, 39.1 +/- 22.9 versus 15.8 +/- 12.4 fmol/ml (P < 0.005), mean +/- SD
      respectively. Higher venous line levels were still observed at the 15 and 60 min
      time points for F60 and GFS Plus 16, but not for SPAN. However, these levels were
      still insignificant compared to levels measured during episodes of anaphylactic
      shock from the literature. Plasma histamine and C5a anaphylatoxin levels did not
      show any increase during HD with SPAN. CONCLUSION: The SPAN membrane did not
      induce significant bradykinin release in dialysis patients on ACE-inhibitor
      therapy. It may therefore be used for high-flux dialysis in such patients.

PMID- 8559492
TI  - Relationship between serum beta 2-microglobulin, bone histology, and dialysis
      membranes in uraemic patients.
AB  - BACKGROUND: beta 2-Microglobulin (beta 2M) is the main constituent of
      osteoarticular amyloid deposits in haemodialysis patients. When dialysed with
      cellulosic (C) membrane such patients present a higher incidence of beta 2M
      related amyloid arthropathy than with synthetic high-flux (SHF) membrane, and
      they have higher serum levels of beta 2M. This could favour beta 2M deposition as
      amyloid fibrils and/or modify bone and cartilage metabolism. METHODS: We examined
      56 uraemic patients dialysed in the same centre for 7.5 +/- 4.8 years (mean +/-
      SD). Based on bone histomorphometry criteria they were classified into either
      high-turnover bone disease (HTBD, 45 patients) or normal/low-turnover bone
      disease (N/LTBD, 11 patients). A subgroup of 30 patients had been dialysed with
      the same dialysis membrane for at least 18 months prior to study, 8 on C and 22
      on SHF membrane. RESULTS: Serum intact parathyroid hormone levels were not
      different between the two patient subgroups. In contrast, serum beta 2M levels
      were higher in patients on C than on SHF membrane: 59.8 +/- 14.1 versus 32.8 +/-
      8.7 mg/l, and so were serum total alkaline phosphatase and osteocalcin levels:
      323 +/- 167 versus 173 +/- 50 IU/l, and 656 +/- 395 versus 288 +/- 263 ng/ml
      respectively. The increase of these serum markers of bone formation was
      associated with a higher bone cell number: osteoblast surface, 21.7 +/- 5.1
      versus 9.8 +/- 11%; osteoclast surface, 4.27 +/- 1.86 versus 1.96 +/- 1.34%; and
      osteoclast number/mm2, 2.85 +/- 1.26 versus 1.27 +/- 0.88 respectively. Serum
      beta 2M was positively correlated with serum osteocalcin (r = 0.58, P < 0.001),
      bone-specific alkaline phosphatase (bAP) (r = 0.46, P < 0.008), and free
      pyridinoline (PYD) (r = 0.62, P < 0.002), and negatively correlated, only for
      HTBD, with osteoid volume: r = -0.40, P < 0.006. Serum beta 2M was higher in
      patients with HTBD than N/LTBD: CONCLUSION: The bone metabolism of chronic
      haemodialysis patients may be influenced by dialysis membrane biocompatibility.
      Moreover, the association of high serum beta 2M with increased bone cell number
      and serum markers of bone turnover suggests that beta 2M is either another marker
      of bone cell activity or an activator of bone cells.

PMID- 8559493
TI  - Predictors of mortality in long-term haemodialysis patients with a low prevalence
      of comorbid conditions.
AB  - BACKGROUND: Total and cardiovascular mortality rates for haemodialysis patients
      are still high despite the continuous improvement of dialysis technology. This
      trend may be a consequence of the increased number of elderly patients and
      patients with concurrent systemic diseases admitted to dialysis programmes. The
      objective of the present investigation was to determine the predictors of
      mortality more closely related to uraemic status and to dialysis treatment by
      studying relatively young haemodialysis patients with a low prevalence of
      comorbid conditions using the Cox proportional hazards model. METHODS: Seventy
      four haemodialysis patients with a low prevalence of extrarenal diseases (mean
      age 44.5 +/- 12.1 years, mean dialysis duration 51.3 +/- 36.1 months) were
      submitted to extensive cardiological and clinical evaluation and followed
      prospectively for a median period of 60.8 months (range: 5.1-79.8). There were
      only three diabetics and all patients denied previous myocardial infarction.
      RESULTS: At follow-up 23 patients had died, 10 of cardiac causes. Five-year
      survival rates were 70% for overall mortality and 83% for cardiac mortality. Age
      over 44 years (relative risk 3.73; 95% confidence interval 1.35-10.26) and serum
      creatinine (inverse correlation) (relative risk 0.73; 95% confidence interval
      0.57-0.94) were shown to be independently associated with global mortality by the
      Cox proportional hazards analysis. Gender, race, dialysis duration, interdialytic
      weight gain, angina, NYHA classification, hypertension, LV hypertrophy, LV
      systolic and diastolic dysfunction, complex ventricular arrhythmias and altered
      myocardial perfusion tests were not significant predictors of overall mortality.
      There were crude associations between cardiac mortality and cardiothoracic and
      Sokolow indices (P < 0.01) and age, NYHA classification, systolic hypertension,
      LV wall and septum hypertrophy, LV dilatation and complex ventricular arrhythmias
      (P < 0.05). CONCLUSION: In the absence of serious comorbid conditions, the
      survival of patients on long-term haemodialysis is influenced by nutritional
      status (as indicated by lower serum creatinine) and age.

PMID- 8559494
TI  - Recombinant tissue plasminogen activator (rt-PA) as first-line therapy for
      declotting of haemodialysis access.
AB  - One of the most common complication in haemodialysis patients is thrombosis of
      the arteriovenous fistula (AVF). Thirty-five patients with a total of 42
      thromboses of the angioaccess were infused via a small needle: (i) into the
      feeding artery (50% of the cases); (ii) into a AVF venous segment of the
      arteriovenous fistula (42.8%); (iii) directly into the thrombus (7.1%), by rt-PA.
      After an initial pulse of 5-10 mg, according to body weight, the drug was
      continuously infused by a pump with the speed automatically programmed in 30
      Brescia-Cimino autologous AV fistulae and 12 polytetrafluoroethylene (PTFE)
      grafts. A complete thrombolysis with return of bruit and thrill was obtained in
      71.4% of the cases using a mean drug dose of 21 mg and an infusion time of 3.8 h.
      All the successful cases underwent haemodialysis via AVF on the same day. No
      bleeding occurred at remote sites. Local bleeding occurred in 16% of the cases;
      in no case was it so severe as to require the suspension of the therapy or blood
      transfusions. The median cumulative duration of patency after thrombolysis was
      32.4 months. Respectively 21, 12 and two patients had a functioning angioaccess
      after 3.6, 32.4 and 36 months from the lytic approach. Failure of the treatment
      was not related to the patients' gender or age, AVF age, route of administration
      of the drug, type of vessel (natural or artificial), or delay between the
      discovery of the fistula occlusion and the start of the therapy. In unsuccessful
      cases an organic lesion of the vessels was documented by angiography or echo
      colour Doppler. In summary, rt-PA local infusion provides a useful means of
      preservation of AV fistulae and may be used as the therapy of first choice in
      dialysis patients without active bleeding or high bleeding risk.

PMID- 8559495
TI  - Haemodynamic changes induced by the correction of anaemia by erythropoietin: role
      of antiplatelet therapy.
AB  - BACKGROUND: In a retrospective study, antiplatelet therapy has been shown to be
      associated with a decreased incidence of erythropoietin-induced hypertension. In
      order to ascertain the role of antiplatelet drugs in the haemodynamic response to
      the correction of anaemia by rHuEpo, 18 patients on chronic haemodialysis who
      started rHuEpo therapy were prospectively studied. METHODS: The subjects were
      randomly assigned to receive or not, one of the following antiplatelet drugs:
      ditazole (3 patients), ticlopidine (3 patients) or aspirin plus dipyridamole (3
      patients). Cardiac index (CI) by echo-Doppler, total peripheral resistance (TPR)
      and mean arterial pressure (MAP) were determined at baseline 10 and 20 weeks
      following the initiation of rHuEpo therapy. rHuEpo therapy was administered
      subcutaneously at the same dose (40 U/kg thrice weekly) during the first 10
      weeks. Ten uraemic patients on haemodialysis who had never received rHuEpo
      therapy served as the control group. RESULTS: One patient in the group without
      antiplatelet drugs discontinued the study due to the development of severe
      hypertension after 12 weeks on rHuEpo therapy. There were no significant
      differences in the haemodynamic parameters at baseline. At 10 weeks, MAP was
      higher in patients without than with antiplatelet drugs or controls untreated
      with rHuEpo (128.5 +/- 28 versus 100.6 +/- 13.5 versus 98.7 +/- 14 mmHg
      respectively, P = 0.0047), TPR was also higher in patients without antiplatelet
      drugs than in the 2 other groups (1919 +/- 433 versus 1576 +/- 359 versus 1418 +/
      324 din.seg.cm-5m2 respectively, P = 0.0231), but CI did not differ among the
      three groups. At 20 weeks, MAP was still higher in patients without antiplatelet
      drugs than in patients with antiplatelet drugs or controls not on rHuEpo therapy
      respectively (112.9 +/- 24.6 versus 91.0 +/- 9.0 versus 101.7 +/- 14.1 mmHg
      respectively, P = 0.075), but at this stage TPR and Cl did not differ among the
      three groups. CONCLUSIONS: These data reinforce the previous observation that
      antiplatelet therapy may prevent the development of rHuEpo-induced hypertension.

PMID- 8559496
TI  - Bidirectional peritoneal transport of albumin in continuous ambulatory peritoneal
      dialysis.
AB  - The present study was undertaken in order to assess bidirectional peritoneal
      kinetics of albumin after simultaneous i.v. and i.p. injection of radioiodinated
      albumin tracers (125I-RISA and 131I-RISA) in eight clinically stable uraemic
      patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The plasma
      volume, intravascular albumin mass (IVM), and overall extravasation rate of
      albumin were not significantly different from that found in healthy controls.
      Albumin flux from the plasma into the peritoneal cavity was 3.71 +/- 0.82 (SD)
      mumol/h, which was only 3% of the overall extravasation rate (137 +/- 52
      mumol/h). Albumin flux from the peritoneal cavity into the plasma was
      substantially lower (0.22 +/- 0.07 mumol/h, P < 0.01). The net peritoneal
      accumulation of the albumin from plasma over 4 h was 14 +/- 3.2 mumol, which was
      significantly lower than the intraperitoneal albumin mass at the end of the
      dialysis (54 +/- 19 mumol, P < 0.01). This indicates that only about 25% of the
      albumin loss during CAPD occurs directly from the plasma. The initial osmotic net
      filtration was 508 +/- 302 ml. The volume flow equivalent to the albumin flux was
      6.3 +/- 1.5 ml/h into the peritoneal cavity and 7.8 +/- 1.9 ml/h back into the
      plasma. Although minor, as compared to the osmotic net filtration (508 ml), the
      albumin flux equivalent volume (31.2 ml) exceeded the steady state filtration
      (25.2 ml) significantly (P < 0.01) during the 4 h investigation. In conclusion,
      albumin flux into the peritoneal cavity is small compared to the overall
      extravasation rate, but our results suggest that CAPD loss of albumin
      predominantly occurs from the subperitoneal interstitial space and only to a
      minor degree directly from the plasma. Albumin flux equivalent volume flow is
      relatively small and most probably represents peritoneal lymph drainage.

PMID- 8559497
TI  - Recombinant erythropoietin improves cognitive function in patients maintained on
      chronic ambulatory peritoneal dialysis.
AB  - Psychometric performance was studied in 17 patients maintained on CAPD. Nine
      patients treated with rHuEpo performed a battery of psychometric tests before
      treatment (haemoglobin mean (SD) 6.8 (0.8) g/dl) and after partial correction of
      anaemia (haemoglobin 9.0 (1.0) g/dl). The same battery of psychometric tests was
      administered to eight patients (haemoglobin 7.7 (0.7) g/dl), matched with the
      treatment group for age, duration of dialysis and social class, who did not
      receive rHuEpo. The National Adult Reading Test was used in all patients to
      estimate the premorbid IQ (the peak cognitive level attained before any cognitive
      deterioration). In the rHuEpo-treated group current IQ, measured by a short form
      of the Wechsler Adult Intelligence Scale--Revised, improved by a mean of 7.2
      points (P < 0.01) and approached estimated premorbid levels, while in the control
      group an improvement by 0.3 points was not significant. Concentration and speed
      of information processing were assessed by the Paced Auditory Serial Addition
      Task and also improved in the treatment group (P < 0.05). Memory, assessed by the
      Rey Auditory Verbal Learning Test, tended to improve in the treatment group with
      amelioration of anaemia, although only the improvement in delayed recall was
      significant. No overall change was seen in either group in the time taken to
      complete the Trail Making Test (part A). These results are consistent with our
      earlier findings in haemodialysis patients, indicating that anaemia makes a
      reversible contribution to uraemic cognitive dysfunction.

PMID- 8559498
TI  - Acute renal and immunological effects of low-dose cyclosporin in humans.
AB  - BACKGROUND: In recent years a reduction of oral cyclosporin A (CsA) dose has been
      adopted to minimize its adverse renal effects. To date, however, little is known
      about the intrinsic renal and immunological effects of low-dose CsA. METHODS:
      Four oral doses of the drug (2, 3, 4 and 5 mg/kg body wt) and placebo (P) were
      randomly administered in two half-doses to seven healthy subjects. Studies were
      performed during water diuresis 4 h after administration of the 2nd half-dose,
      i.e. when the biological activity of the drug is considered maximal. Renal
      function was evaluated after all doses. In the same subjects, the levels of
      interleukin-2 (IL-2) and IL-2 receptor (IL-2R), that are the main immunological
      targets of CsA, were measured in the supernatant of peripheral blood mononuclear
      cells cultured with phytohaemagglutinin (PHA) after P, 3 and 5 mg/kg of the drug.
      RESULTS: CsA induced a dose-dependent and proportional decrease of GFR and RPF
      associated with increasing renal vascular resistances (RVR) in presence of
      unmodified blood pressure. Similarly, Na+ urinary excretion decreased in a dose
      dependent manner due to both GFR reduction and to an higher tubular reabsorption
      mainly localized at the level of the proximal nephron. All these changes were
      significant only after 4 and 5 mg/kg. A significant suppression of PHA-stimulated
      IL-2 and IL-2R cell release was observed following 5 mg/kg only. CONCLUSIONS:
      This study suggests that nephrotoxic and immunosuppressive effects of low-dose
      CsA are strictly linked.

PMID- 8559499
TI  - Fish oil and cyclosporin A-induced renal hypoperfusion in kidney-transplanted
      patients.
AB  - BACKGROUND: Dietary supplementation with fish oil has been said to improve renal
      function in cyclosporin A (CsA)-treated subjects. METHODS: Renal function and the
      acute renal haemodynamic and tubular response to an oral CsA-dose (3 mg/kg) were
      investigated before and after 12 weeks of fish oil supplementation (6 g/day) in
      12 low-dose CsA-treated kidney-transplanted patients (s-creatinine, 124 +/- 24
      mumol/l, mean +/- SD). After an overnight fast, ten l-h renal clearance periods
      were performed, two periods before and eight after CsA-ingestion. An additional
      control clearance study without CsA intake was performed in six subjects.
      RESULTS: Fish oil did not change baseline values of the effective renal plasma
      flow (ERPF) or the glomerular filtration rate (GFR). Compared to the control
      study, CsA decreased GFR and ERPF significantly on average 20 +/- 3% (P < 0.01)
      and 23 +/- 3% (P < 0.01) respectively, 4-6 h after peak CsA blood concentration
      with no additional effect of fish oil. CsA also significantly decreased the renal
      clearance of lithium, used as an index of proximal tubular outflow, with no
      impact of dietary fish oil. CONCLUSION: Fish oil supplementation had no effect on
      baseline renal function or CsA-induced hypoperfusion in stable renal transplant
      recipients treated with a low maintenance dose of CsA.

PMID- 8559501
TI  - Acute renal failure due to naftidrofuryl oxalate Praxilene overdose in a kidney
      transplant recipient.

PMID- 8559500
TI  - Potential nephrotoxicity of intravenous infusions of naftidrofuryl oxalate.
AB  - We report two cases of acute renal failure in patients with arteriosclerosis
      obliterans treated by intravenous infusion of naftidrofuryl oxalate. At renal
      biopsy the histological lesions were identical with those found in ARF due to
      hyperoxaluria of other causes, revealing tubular epithelial necrosis and massive
      intratubular precipitation of calcium oxalate monohydrate (C1) crystals. A second
      study was then conducted in four other patients with arteriosclerosis obliterans
      to evaluate serum and urinary levels of oxalate, and crystalluria during the
      intravenous administration of 800 mg of naftidrofuryl oxalate per day for 10
      days. During the course of treatment, the serum and urinary oxalate levels were
      found to increase substantially, with the gradual onset of massive C1
      crystalluria. These results indicate that naftidrofuryl oxalate was responsible
      for the acute renal failure in the first two patients. High intravenous doses of
      naftidrofuryl oxalate must be used cautiously, with close surveillance of renal
      function.

PMID- 8559502
TI  - Etoposide: sometimes the drug of choice in Wegener's granulomatosis?

PMID- 8559503
TI  - Morning glory optic disc anomaly associated with chronic renal disease.

PMID- 8559504
TI  - Hyperthyroidism in haemodialysis patients: report on a case and review of the
      literature.

PMID- 8559505
TI  - Heparin-induced thrombocytopenia during continuous haemofiltration.

PMID- 8559506
TI  - Metastatic renal-cell carcinoma developing in two recipients of renal grafts
      derived from the same donor.

PMID- 8559507
TI  - Acyclovir-associated encephalopathy, lack of relationship between acyclovir
      levels and symptoms.

PMID- 8559508
TI  - A dialysis patient with fatigue and ascites.

PMID- 8559509
TI  - Zinc supplementation and hepatitis B vaccination in chronic haemodialysis
      patients: a multicentre study.

PMID- 8559510
TI  - Potential role for antiphospholipid antibodies in renal thrombotic
      microangiopathy induced by interferon-alpha.

PMID- 8559511
TI  - Can hypercalcaemia be avoided during oral calcitriol pulse therapy of secondary
      hyperparathyroidism in haemodialysis patients?

PMID- 8559512
TI  - Is calcitonin a helper of phosphate binders in the control of renal
      osteodystrophy?

PMID- 8559513
TI  - About C3NeF activity and acute post-streptococcal glomerulonephritis.

PMID- 8559514
TI  - The biosynthesis of pyridoxine.

PMID- 8559515
TI  - The biosynthesis of shikimate metabolites.

PMID- 8559516
TI  - A United States national reference for fetal growth.
AB  - OBJECTIVE: To develop a current national fetal growth curve that can be used as a
      common reference point by researchers to facilitate investigations of the
      predictors and consequences of small and large for gestational age delivery.
      METHODS: Single live births to United States resident mothers in 1991 (n =
      3,134,879) were used for the development of this curve, which was compared with
      four previously published fetal growth curves. Techniques were developed to
      address cases with implausible birth weight-gestational age combinations and to
      smooth fetal growth curves across gestational age categories. RESULTS: In
      general, the previously published fetal growth curves underestimated the 1991
      United States reference curve. This underestimation is most apparent during the
      latter weeks of gestation, approximately 33-38 weeks. CONCLUSION: Our findings
      indicate that the prevalence of fetal growth restriction (FGR) will vary
      markedly, depending on the fetal growth curve used. Furthermore, many previously
      published fetal growth curves no longer provide an up-to-date reference for
      describing the distribution of birth weight by gestational age and for
      determining FGR that is consistent with the most recent live birth data for the
      entire United States.

PMID- 8559517
TI  - Do growth-retarded premature infants have different rates of perinatal morbidity
      and mortality than appropriately grown premature infants?
AB  - OBJECTIVE: To determine if perinatal morbidity and mortality differ in growth
      retarded, small for gestational age (SGA), premature infants and appropriate for
      gestational age (AGA) infants. METHODS: All consecutive, singleton, nondiabetic,
      preterm pregnancies delivered over a 15-year period were analyzed. Infants were
      categorized as SGA (at or below the tenth percentile) or AGA (11th to the 89th
      percentiles), then stratified by birth weight and gestational age categories.
      Perinatal morbidity and mortality were examined. RESULTS: We studied 4183 preterm
      deliveries, 1012 of them SGA and 3171 of them AGA. Overall, we found
      significantly higher rates of fetal and neonatal death in the SGA group.
      Stratification by gestational age revealed significantly higher rates of neonatal
      death for the SGA group compared with the AGA group in each gestational age
      category. Overall, comparison also revealed significantly higher rates of fetal
      heart rate abnormality in the SGA group but no difference in neonatal sepsis,
      birth trauma, cesarean delivery, hyaline membrane disease, or congenital
      anomalies. CONCLUSION: Growth-retarded premature infants have a significantly
      higher risk of morbidity and mortality, both before and after delivery, than do
      appropriately grown infants.

PMID- 8559518
TI  - Influence of acid-base status at birth and Apgar scores on survival in 500-1000-g
      infants.
AB  - OBJECTIVE: To evaluate the influence of acid-base status at birth and Apgar
      scores on survival in very low birth weight infants. METHODS: We evaluated 1073
      infants born alive and weighing 500-1000 g during 1979-1991; 658 had umbilical
      artery gas values examined. Apgar scores were assigned at 1 and 5 minutes after
      birth. Umbilical artery blood samples were collected at delivery for pH, carbon
      dioxide pressure (PCO2), and bicarbonate. Infants were grouped at 23-24, 25-26,
      27-28, and 29 weeks or more. Using survival as the dependent variable, multiple
      logistic regression analyses were performed controlling for gestational age,
      birth weight, plurality, antenatal glucocorticoid use, mode of delivery, and year
      of birth, as well as for Apgar scores and cord blood gases. RESULTS: In every
      gestational age grouping, compared with infants with a pH lower than 7.05,
      survival was higher in infants with an umbilical artery pH of 7.05 or higher,
      significantly so at 27-28 weeks. There was no consistent relationship between
      umbilical artery PCO2 or bicarbonate and survival. However, with the exception of
      the 1-minute Apgar score at 23-24 weeks, the relationship of Apgar scores to
      survival was significant in all gestational age periods. Using multiple logistic
      regression analyses, the only significant relationships between any of the cord
      blood gases, Apgar scores, and mortality involved low 1-minute (odds ratio [OR]
      2.7 [95% confidence interval (CI) 2.0-3.6]) and low 5-minute Apgar scores (OR 2.8
      [95% CI 2.0-3.8]) and a bicarbonate less than 21 mEq/L (OR 1.6 [95% CI 1.1-2.4]).
      CONCLUSION: One- and 5-minute Apgar scores are better predictors of survival than
      umbilical artery blood gases in neonates weighing 500-1000 g at birth.

PMID- 8559519
TI  - Amniotic fluid meconium: a fetal environmental hazard.
AB  - OBJECTIVE: To investigate the hypothesis that meconium aspiration syndrome, the
      major hazard of meconium during labor, may be associated with superimposed fetal
      acute acidemia. METHODS: Umbilical artery blood gases were measured in 7816 term
      pregnancies with meconium in the amniotic fluid (AF) and the results were
      correlated with intrapartum and neonatal outcomes. RESULTS: Sixty-nine (1%)
      infants developed meconium aspiration syndrome and 31 (45%) of these were in
      association with fetal acidemia at birth. Moreover, umbilical blood gas analysis
      and intrapartum events suggested that the fetal acidemia linked to meconium
      aspiration was an acute event rather than a long-duration process, which might be
      expected if meconium was itself a marker of an antecedent fetal asphyxial event.
      CONCLUSION: Meconium in the AF may be a fetal environmental hazard when acidemia
      supervenes rather than solely a marker of preexisting fetal compromise leading to
      the release of meconium.

PMID- 8559520
TI  - The effect of maternal blood contamination on amniotic fluid glucose and white
      blood cell count from preterm gestations.
AB  - OBJECTIVE: To determine the influence of maternal blood contamination on amniotic
      fluid (AF) glucose and white blood cell count (WBC). METHODS: Amniotic fluid from
      23 preterm, nondiabetic pregnant women was studied. Maternal blood was added to
      the AF at increasing concentrations, and glucose and WBCs were assessed. RESULTS:
      The median AF glucose in the uncontaminated specimen was 43 mg/dL (range 11-86).
      Median glucose levels were unchanged by the addition of maternal blood until a
      mean +/- standard deviation AF red blood cell count of 63,000 +/- 22,000/mm3 was
      exceeded, at which time the median glucose level significantly increased to a
      median of 45 mg/dL (range 19-90). The ratio of observed to expected values of
      WBCs ranged from 0.12-1.8, regardless of the level of maternal blood
      contamination. CONCLUSION: Glucose levels in preterm AF-containing maternal blood
      are accurate in all except the most heavily contaminated specimens. Accurate
      determination of the WBC in contaminated AF is difficult.

PMID- 8559521
TI  - Risk factors for neonatal sepsis.
AB  - OBJECTIVE: To determine the associations between maternal characteristics,
      intrapartum events, and neonatal sepsis by multivariate analysis. METHODS: We
      enrolled 823 women from a high-risk population and analyzed maternal and neonatal
      demographic and outcome variables with univariate analysis and multivariate
      logistic modeling. RESULTS: Two-hundred sixteen women (26%) were colonized with
      group B streptococci, 82 (10%) developed chorioamnionitis, and 141 (17%)
      delivered prematurely. Culture-proven neonatal sepsis or meningitis was found in
      15 of 833 (1.8%) neonates, and 101 of the remaining 818 (12.3%) infants were
      suspected to have sepsis or pneumonia. Multivariate analysis of risk factors for
      proven neonatal sepsis demonstrated a statistically significant association with
      decreasing gestational age, duration of internal monitoring for more than 12
      hours (odds ratio [OR] 7.2, 95% confidence interval [CI] 1.6-32.2), maternal
      group B streptococcal infection (OR 4.2, 95% CI 1.4-13.1), chorioamnionitis (OR
      4.4, 95% CI 1.2-16.1), and endometritis (OR 6.4, 95% CI 1.2-34.2). CONCLUSION:
      Through the use of multivariate modeling, we determined that chorioamnionitis or
      endometritis, preterm delivery, group B streptococcal colonization, and a
      prolonged duration of internal monitoring are independent risk factors for
      neonatal sepsis. We postulate that the presence of a foreign body that traverses
      the birth canal may facilitate ascending peripartal infection.

PMID- 8559522
TI  - Pregnancy rates among women infected with human immunodeficiency virus.
      Adult/Adolescent HIV Spectrum of Disease Project Group.
AB  - OBJECTIVE: To examine pregnancy rates among women infected with human
      immunodeficiency virus (HIV). METHODS: We used data from an ongoing survey of
      medical records of 3915 women who were 15-44 years of age, infected with HIV, and
      who received care between January 1990 and August 1994 in more than 90 clinics,
      hospitals, and private practices in 11 United States cities. RESULTS: At
      enrollment, 570 (14%) of these women were pregnant. Pregnancy rates at entry
      varied significantly (P < .05) by age in years (15-19 [47%], 20-24 [30%], 25-29
      [18%]; 30-34 [11%]; 35-39 [5%]; 40-44 [2%]); clinical status (with AIDS
      opportunistic illness [3%], without AIDS opportunistic illness [17%]; and race
      ethnicity (white [12%], black [17%], Hispanic [8%], Asian [0%], Native American
      [30%]) but not by mode of exposure (injecting drug use [10%], heterosexual
      contact [15%], and blood transfusion [12%]). After enrollment, 5.8% of women
      became pregnant each year. New pregnancies were significantly less likely to
      occur among women with an AIDS opportunistic illness (adjusted rate ratio 0.4,
      95% confidence interval [CI] 0.2-0.6), and significantly more likely to occur
      among women who were less than 25 years of age (adjusted rate ratio 8.3, 95% CI
      5.3-13.2) and who were black (adjusted rate ratio 1.6, 95% CI 1.2-2.1). Among
      women who were pregnant at enrollment or during observation, 12% were pregnant
      more than once. CONCLUSIONS: High rates of pregnancy at entry to medical care
      among HIV-infected women stress the importance of counseling and voluntary
      testing as routine obstetric-gynecologic practice. In some groups, rates of new
      pregnancies remain high; standard HIV care for women should include family
      planning services and assurance that if a woman chooses to practice
      contraception, contraceptives will be available and affordable.

PMID- 8559523
TI  - Pregnancy in sickle cell disease: experience of the Cooperative Study of Sickle
      Cell Disease.
AB  - OBJECTIVE: To determine the maternal and fetal outcomes of pregnancy in women
      with sickle cell disease. METHODS: The subjects were part of a cohort recruited
      from 19 centers for a prospective study of the clinical course of sickle cell
      disease. Each participant was evaluated using a structured protocol in which
      steady-state data and information on both sickle- and non-sickle-related events
      were collected. The rates of antepartum and intrapartum complications were
      tallied for pregnancies carried to delivery. Fetal outcome was assessed according
      to gestational age, birth weight, and Apgar score. Differences among genotypes in
      event rates were assessed using Fisher exact test. Differences in gestational age
      and birth weight, and predictors of these outcomes, were assessed using analyses
      of covariance. RESULTS: Two hundred eighty-six of the 445 reported pregnancies
      proceeded to delivery. Non-sickle-related antepartum and intrapartum complication
      rates were comparable with those of African-American women who did not have
      sickle cell disease. One of the two deaths observed during this study was
      directly related to the presence of sickle cell disease. Rates of maternal
      morbidity from sickle cell disease were the same during pregnancy as during the
      nonpregnant state. Ninety-nine percent of those pregnancies carried to delivery
      resulted in a live birth. Twenty-one percent of the infants born to women of the
      SS genotype were small for gestational age (SGA). Preeclampsia and acute anemic
      events were identified as risk factors for SGA infants. CONCLUSIONS: Those caring
      for women with sickle cell disease should support them if they desire to have
      children.

PMID- 8559524
TI  - Diurnal blood pressure difference in the assessment of preeclampsia.
AB  - OBJECTIVE: To evaluate diurnal variation in blood pressure (BP) in normal
      gravidas and those with preeclampsia, using ambulatory BP monitoring. METHODS: A
      cross-sectional comparative observational study was performed in three teaching
      hospital maternity units. Twenty-four normotensive and 24 preeclamptic women who
      were similar in age, weight, and mean duration of gestation (35 weeks) were
      studied. Diurnal variation and BP measurement were assessed using ambulatory BP
      monitors validated for use in pregnancy and for which normal reference ranges for
      pregnancy have been derived. RESULTS: At night, the BP fall was less in
      preeclamptic women than in normotensive women. The day-night BP difference
      decreased as average BP rose (diastolic gradient = -0.54 [95% confidence interval
      (CI) -0.77 to -0.31], systolic gradient = -0.36 [95% CI -0.58 to -0.14], where
      gradient denotes a unit increase in BP leading to an increase or decrease in the
      day-night difference). CONCLUSION: The decrease in day-night BP difference
      observed in preeclampsia is inversely related to average BP. This blunting of the
      day-night BP difference may be a useful adjunctive measure of disease severity in
      preeclampsia.

PMID- 8559525
TI  - Use of the Centers for Disease Control and Prevention childhood lead poisoning
      risk questionnaire to predict blood lead elevations in pregnant women.
AB  - OBJECTIVE: To assess the accuracy of a questionnaire developed by the Centers for
      Disease Control and Prevention (CDC), given to pregnant women for identification
      of children at risk for lead poisoning. METHODS: The study population consisted
      of all 314 new prenatal patients enrolled in health department clinics in 1990
      1992. Lead was measured in venous blood, and patients completed written
      questionnaires to gather information about lead exposure risk factors. The
      relationship between elevated maternal blood lead levels (at or greater than 10
      micrograms/dL or 0.483 mumol/L) and responses to the CDC questionnaire and other
      questions were examined using chi 2 statistical analysis. RESULTS: Two hundred
      ninety-nine women provided responses to questions about lead exposure risk.
      Thirty-nine women (13%) had elevated blood lead levels. A woman with a positive
      response to at least one CDC question was more likely to have elevated blood lead
      than a woman who answered negatively to all four CDC questions (relative risk =
      2.39, 95% confidence interval 1.17-4.89; P = .01). Using the CDC definition of
      high risk ("yes" to at least one question), the questionnaire had a sensitivity
      of 75.7% and a negative predictive value of 93.1%. A questionnaire that combined
      housing conditions, smoking status, and high consumption of canned foods had a
      sensitivity of 89.2% and a negative predictive value of 96.4%. A high prevalence
      of elevated blood lead in children living with women with elevated blood lead was
      observed. CONCLUSION: Querying pregnant women about risk factors for lead
      exposure can aid in assessing prenatal lead exposure risk. The sensitivity and
      negative predictive value of the CDC questionnaire, when used with high-risk
      women, are comparable to its reported accuracy in young children.

PMID- 8559526
TI  - Prognostic significance of unexplained elevated amniotic fluid alpha-fetoprotein.
AB  - OBJECTIVE: To compare the prognostic values of unexplained elevated amniotic
      fluid alpha-fetoprotein (AF AFP > or = 2.0 multiples of the median [MoM]) and
      unexplained elevated maternal serum alpha-fetoprotein (MSAFP > or = 2.5 MoM).
      METHODS: We accessed a data base containing the results of MSAFP screening tests,
      genetic amniocenteses, and pregnancy outcome data on all women undergoing second
      trimester genetic amniocentesis from October 1988 through August 1994. After
      excluding all patients whose elevated AFP levels had any identifiable cause
      (positive AF acetylcholinesterase, AF blood contamination, fetal malformation or
      aneuploidy, multiple gestation, etc), 5743 cases were analyzed. Relative risks
      (RR) for selected pregnancy complications were determined. RESULTS: Elevated
      MSAFP, with any AF AFP, was associated with fetal growth restriction (RR 2.5, 95%
      confidence interval [CI] 1.4-4.4), stillbirth (RR 3.5, 95% CI 1.4-8.3),
      preeclampsia (RR 2.8, 95% CI 1.1-7.0), and preterm delivery (RR 2.8, 95% CI 2.3
      3.4). Elevated AF AFP, with any MSAFP, was associated with preeclampsia (RR 4.4,
      95% CI 2.0-10.0) and preterm delivery (RR 1.7, 95% CI 1.3-2.4). Elevation of both
      AF AFP and MSAFP was associated with preterm delivery (RR 4.0, 95% CI 2.8-5.7).
      When elevated AF AFP was found in association with a normal MSAFP, the RR to
      develop preeclampsia was 4.6 (95% CI 1.9-11.2). CONCLUSION: Maternal serum alpha
      fetoprotein is a better predictor of late pregnancy complications than AF AFP.
      However, unexplained elevated AF AFP appears to be especially predictive of
      preeclampsia.

PMID- 8559527
TI  - Elevated second-trimester maternal serum hCG alone or in combination with
      elevated alpha-fetoprotein.
AB  - OBJECTIVE: To evaluate the clinical significance of a second-trimester elevated
      maternal serum hCG in women carrying singleton, chromosomally normal fetuses.
      METHODS: The results of second-trimester maternal serum screening (alpha
      fetoprotein [MSAFP], hCG, and unconjugated estriol) for 25,438 women were
      reviewed, and those with hCG values exceeding 3.0 multiples of the median (MoM)
      were identified. A control population was selected only on the basis of samples
      accessioned by the laboratory at the same time as the study group. Follow-up
      information was collected from physicians' offices for both groups. Incidence of
      fetal or neonatal loss (spontaneous abortion, fetal death, and neonatal death
      combined), preterm birth (before 37 weeks' gestation), small for gestational age,
      and preeclampsia were compared. RESULTS: Three hundred twenty-two women (1.3%)
      had hCG levels exceeding 3.0 MoM. In addition to chromosomal abnormalities and
      fetal death at the time of testing, this group showed a significantly higher
      incidence of fetal or neonatal death, preterm birth, low birth weight, and
      preeclampsia than did controls. For patients with elevated second-trimester hCG,
      many of the preterm deliveries occurred before 34 weeks' gestation. Logistic
      regression analysis indicated that hCG, MSAFP, and race were significant
      independent factors in predicting risk for adverse outcome. CONCLUSIONS: Similar
      to elevated AFP, elevated hCG is associated with poor pregnancy outcome. By
      combining the results of the two tests, it may be possible to improve
      substantially the identification of patients at very high risk for adverse
      outcomes.

PMID- 8559528
TI  - A randomized comparison of prostaglandin E2, oxytocin, and the double-balloon
      device in inducing labor.
AB  - OBJECTIVE: To compare the efficacy of three methods for ripening and dilating the
      unfavorable cervix for induction of labor. METHODS: Pregnant women having an
      indication for induction of labor with a singleton vertex fetus, intact
      membranes, and Bishop score of no more than 4 were randomized to one of three
      induction methods: intravaginal prostaglandin (PG) E2 tablets (3 mg) followed by
      a second dose if labor did not start; continuous intravenous oxytocin drip; or
      the Atad Ripener Device, with inflation of both balloons and removal after 12
      hours. For all patients, the cervix was assessed by the same investigator before
      induction and 12 hours later. RESULTS: Thirty subjects were included in the PGE2
      group, 30 in the oxytocin group, and 35 in the Atad Ripener Device group. The
      postpartum course was comparable in all. The change in Bishop score in the PGE2
      and Atad Ripener Device groups was significantly better than in the oxytocin
      group (median and range of 5[0-9] and 5[0-7], respectively, versus 2.5 [0-9]; P <
      .01). Cervical dilation more than 3 cm was more frequent in the Atad Ripener
      Device group compared with both the PGE2 and oxytocin groups (85.7 versus 50 and
      23.3%, respectively; P < .01). The trial of induction failed in only two patients
      (5.7%) in the Atad Ripener Device group, compared with six (20%) in the PGE2 and
      16 (53.3%) in the oxytocin groups (P < .001). Mean (+/- standard deviation)
      induction-to-delivery interval was 21.3 +/- 7.0 hours in the Atad Ripener Device
      group, 23.2 +/- 12.5 hours in the PGE2 group, and 28.2 +/- 14.7 hours in the
      oxytocin group. The success rate for vaginal delivery was significantly better in
      the Atad Ripener Device and PGE2 groups compared with the oxytocin group (77.1
      and 70%, respectively, versus 26.7%; P < .01). CONCLUSION: The Atad Ripener
      Device had a significantly better success rate for cervical dilation and a lower
      failure rate than those for PGE2 and oxytocin. The PGE2 and Atad Ripener Device
      groups had better results than the oxytocin group in regard to Bishop score
      change and induction-to-delivery interval. The Atad Ripener Device may be a
      superior method for cervical ripening and labor induction in patients with
      unfavorable cervices.

PMID- 8559529
TI  - Prostaglandin E2 gel for cervical ripening in patients with an indication for
      delivery.
AB  - OBJECTIVE: To determine if labor can be induced safely and efficiently in
      patients with a medical or obstetric indication for delivery before 41 completed
      weeks of gestation by pre-induction cervical ripening with prostaglandin (PG) E2
      gel. METHODS: One hundred eighteen women with confirmed indication for induction
      of labor before 41 completed weeks were randomized in a double-blind fashion to
      either intracervical PGE2 gel or placebo before induction by a standard oxytocin
      protocol. Data regarding the change in Bishop score, interval to complete
      dilation, maximal oxytocin dose required to establish labor, and route of
      delivery were collected. Apgar scores and umbilical artery pH were also recorded.
      RESULTS: The maximum oxytocin dose required to establish progressive labor was
      significantly lower in the PGE2 group (10.06 +/- 8.50 versus 13.35 +/- 9.27
      mU/minute, P = .014). The cesarean rate was also significantly lower in the PGE2
      group (13.1 versus 31.6%, P = .016). CONCLUSION: Pre-induction intracervical
      deposition of 1 mg PGE2 gel decreased the amount of oxytocin required to induce
      progressive labor and decreased the cesarean rate in patients who had medical or
      obstetric indications for delivery before 41 completed weeks. This was
      accomplished without negative effect on Apgar score or umbilical artery pH.

PMID- 8559530
TI  - Maternal blood C-reactive protein, white blood cell count, and temperature in
      preterm labor: a comparison with amniotic fluid white blood cell count.
AB  - OBJECTIVE: To compare the diagnostic and prognostic performance of maternal blood
      C-reactive protein, white blood cell count (WBC), and temperature with that of
      amniotic fluid (AF) WBC in preterm labor. METHODS: One hundred two women with
      preterm labor and intact membranes were studied. Maternal blood was collected to
      measure C-reactive protein concentration and WBC, and maternal temperature was
      also measured. Amniotic fluid obtained by amniocentesis was cultured and WBC
      determined. Receiver operating characteristic curve, logistic regression, and
      survival techniques were used for analysis. RESULTS: Patients with acute
      histologic chorioamnionitis had significantly higher median C-reactive protein
      concentration, WBC, temperature, and AF WBC than patients without this lesion (P
      < .05). Receiver operating characteristic curve and survival analysis
      demonstrated that an elevated C-reactive protein, WBC, or AF WBC was strongly
      associated with the likelihood of histologic chorioamnionitis, shorter interval
      to delivery, clinical chorioamnionitis, and neonatal morbidity (P < .05 for
      each). Of all the tests, AF WBC was the best independent predictor of a positive
      AF culture (odds ratio [OR] 16.8), interval to delivery (hazard ratio 5.7),
      clinical chorioamnionitis (OR 15.2), neonatal sepsis (OR 16.8), and significant
      neonatal complications (OR 7.4), after other confounding variables were adjusted
      (P < .05 for each). CONCLUSION: An elevated C-reactive protein, WBC, or AF WBC
      identified patients with intrauterine infection and adverse perinatal outcomes.
      Amniotic fluid WBC was a better independent predictor of these outcomes than C
      reactive protein, WBC, or temperature.

PMID- 8559531
TI  - T and J vertical extensions in low transverse cesarean births.
AB  - OBJECTIVE: To determine the frequency of T and J extensions in low transverse
      cesarean births at a regional perinatal center, identify the indications for
      these incisions, and evaluate the associated complications. METHODS: We reviewed
      the medical records of 56 patients delivered between January 1988 and November
      1994 by low transverse cesarean birth requiring vertical extension of the
      incision into-the upper uterine segment. Cases of extension were compared with
      controls matched for gestational age, presentation, and indication for cesarean
      delivery. Data collected included demographic information, indications for
      extension, extension type, estimated blood loss, intraoperative complications,
      and length of hospital stay. Paired Student t test and McNemar test were used for
      statistical analysis. RESULTS: Vertical extensions were performed in 1.3% (95%
      confidence interval 0.42-2.26%) of low transverse incisions over a 7-year period.
      The most common indications were malpresentation (n = 31), poorly developed lower
      uterine segment (n = 12), and fetal head deeply arrested in the midpelvis (n =
      6). Estimated blood loss was greater for patients requiring an extension (990 +/-
      310 mL) compared with controls (790 +/- 150 mL), as were differences in
      preoperative versus postoperative hemoglobin and hematocrit (P < .05). Surgical
      complications were observed in 28 of 56 (50%) subjects with a uterine extension,
      including excessive blood loss (n = 20), broad ligament hematomas or extensions
      (n = 4), cervical lacerations (n = 4), and uterine artery lacerations (n = 4).
      Patients with vertical extensions also had longer hospital stays (4.6 +/- 1.6
      versus 3.8 +/- 1.1 days) (P < .05). CONCLUSIONS: Low transverse uterine incisions
      may be inadequate for the safe delivery of a fetus in cases of malpresentation,
      preterm birth, and poor development of the lower uterine segment. Used to
      complete these difficult deliveries, T and J extensions are often associated with
      intraoperative complications and prolonged hospital stays compared with controls.

PMID- 8559532
TI  - Least microtransfusion from mother to fetus in elective cesarean delivery.
AB  - OBJECTIVE: To examine the variability of maternal-fetal microtransfusion in
      different modes of delivery, as measured by hepatitis B surface antigen (HBsAg)
      and placental alkaline phosphatase. METHODS: We recruited 97 HBsAg-positive
      pregnant women. The mode of delivery included elective cesarean in 16, normal
      spontaneous vaginal delivery in 56, vacuum or forceps delivery in 12, and
      emergency cesarean after labor in 13. We measured HBsAg and placental alkaline
      phosphatase levels in 97 pairs of maternal and fetal blood samples collected at
      delivery. RESULTS: The mean maternal placental alkaline phosphatase levels did
      not differ among these four groups. The mean cord placental alkaline phosphatase
      level of the elective cesarean group was the lowest (P < .05). All samples of
      cord sera for this group were negative for HBsAg, compared with 38 of 56, eight
      of 12, and seven of 13 in the spontaneous vaginal, vacuum or forceps, and
      emergency cesarean groups, respectively (P < .05). CONCLUSION: The level of
      mother-to-fetus microtransfusion least in the elective cesarean group, as
      revealed by both the lowest cord placental alkaline phosphatase and HBsAg levels.
      These observations may have implications for reducing perinatal transmission of
      blood-borne viruses.

PMID- 8559533
TI  - Nitric oxide synthase activities in human myometrium and villous trophoblast
      throughout pregnancy.
AB  - OBJECTIVE: To study the changes in nitric oxide synthase activities in human
      myometrium and trophoblast throughout pregnancy and around delivery. METHODS:
      Samples of villous trophoblast were collected from women undergoing elective
      cesarean delivery at term (n = 12) or voluntary termination of pregnancy in the
      first (n = 27) or second (n = 11) trimesters of pregnancy. Myometrial samples
      were obtained from nonpregnant women undergoing hysterectomy (n = 5) and pregnant
      women both before (n = 7) and after (n = 7) the onset of spontaneous labor at
      term. Nitric oxide synthase activity was quantified for homogenized samples using
      the L-citrulline assay in the presence and absence of calcium. RESULTS: The
      highest levels of nitric oxide synthase activity were found in first-trimester
      villi (range 2-29 nmol L-citrulline/minute/g protein), with a significant fall in
      activity in the third trimester (range 2-10 nmol L-citrulline/minute/g protein; P
      < .001 for both calcium-dependent and calcium-independent activity). Myometrial
      activities were relatively low compared with those in the trophoblast (0-2 nmol L
      citrulline/minute/g protein), with no significant differences in calcium
      dependent activities between subgroups. Myometrial calcium-independent activities
      were lower in pregnant than in nonpregnant women (P = .007), with those in labor
      having levels higher than those not in labor (P = .048). CONCLUSION: Levels of
      nitric oxide synthase activity are relatively high in villous trophoblast,
      particularly during the first trimester. Although the contribution to total
      nitric oxide production in the uterus by myometrial nitric oxide synthase appears
      to be relatively small, nitric oxide produced by the trophoblast may play a role
      in maintaining uterine quiescence by a paracrine effect. Further work is needed
      to test this hypothesis and explore other possible roles for trophoblast-derived
      nitric oxide in early pregnancy.

PMID- 8559534
TI  - Linea alba pigmentation and umbilical deviation in nulliparous pregnancy: the
      ligamentum teres sign.
AB  - OBJECTIVE: To determine the incidence and direction of umbilical deviation in
      pregnancy at term in nulliparas with linea alba pigmentation. METHODS: All women
      attending one prenatal clinic over a period of 19 months were available. Subjects
      studied were the 315 nulliparas whose pregnancies had reached at least 37 weeks'
      gestation. The presence of linea alba pigmentation, with or without umbilical
      flattening and/or deviation, was assessed with the woman lying symmetrically on
      her back on an examination couch. RESULTS: Forty-four of the 315 women (14%) had
      sufficient pigmentation for assessment; 27 of the 44 (61.4%) were born in Asia or
      the Indian subcontinent, although such women comprised only 13.5% of the clinic
      population. In 31 of the 44 women (70.5%), the umbilicus and supra- or
      infraumbilical linea nigra was deviated to the right side, and in 13 it remained
      in the midline; in none was there deviation to the left side. CONCLUSION:
      Displacement of the umbilicus and adjacent structures commonly occurs in term
      pregnancy; pressure of the uterus on the ligamentum teres and falciform ligament
      determines that displacement is invariably toward the right side.

PMID- 8559535
TI  - Long-term effects of vaginal dissection on the innervation of the striated
      urethral sphincter.
AB  - OBJECTIVE: To study the long-term effects of vaginal dissection on the
      innervation of the striated urethral sphincter. METHODS: Perineal nerve terminal
      motor latency was measured before and 8 weeks and 1 year after anterior
      colporrhaphy, colpoperineoplasty, and vaginal hysterectomy in 33 women, 19 of
      whom also underwent endoscopic suspension of the bladder neck. RESULTS: In the
      entire series, the mean perineal nerve terminal motor latency was prolonged
      before surgery over that in normal continent women and further prolonged 8 weeks
      and 1 year postoperatively. In the subjects who underwent vaginal hysterectomy
      and anterior colporrhaphy, perineal motor latencies were not significantly
      prolonged at the 8-week postoperative follow-up and had almost returned to
      preoperative values 1 year later. However, in those who underwent additional
      endoscopic bladder neck suspension, perineal motor latencies were prolonged at
      both postoperative follow-up examinations. Perineal motor latencies were
      unchanged 1 year postoperatively in continent patients (N = 19) but were
      prolonged in incontinent patients (N = 14). CONCLUSION: Vaginal dissection,
      especially during endoscopic bladder neck suspension, can worsen preexisting
      perineal neuropathy in patients with pelvic relaxation and stress incontinence.

PMID- 8559536
TI  - Long-term effect of pelvic floor muscle exercise 5 years after cessation of
      organized training.
AB  - OBJECTIVE: To evaluate clinically and urodynamically the effect of pelvic floor
      muscle exercise on genuine stress incontinence 5 years after cessation of a
      structured training program. METHODS: All 23 women who had participated in a 6
      month intensive pelvic floor muscle exercise regimen participated in the follow
      up study. Mean age was 50.7 years (range 30-70). The assessment included history
      by interview, use of subjective rating instruments (leakage index and social
      activity index), vaginal palpation, measurement of pelvic floor muscle strength
      by use of vaginal pressure measurement, cystometry, urethral pressure profiles
      during cough, and pad test with standardized bladder volume. RESULTS: Three of 23
      women had been treated surgically. Sixteen (70%) were exercising the pelvic floor
      muscles once a week or more. This included two of the women treated surgically.
      Of the 20 women not treated surgically, 70% were satisfied and did not want
      further treatment. Fifteen of 20 (75%) did not show any visible leakage during
      cough, and 11 had positive closure pressure during cough. There was a
      statistically significant increase in the scores of the leakage index and the pad
      test (P < .05) but not on the social activity index (P = .09). Pelvic floor
      muscle strength was reduced from a mean of 22 cm H2O (95% confidence interval
      [CI] 17-26.9) to 19.1 (95% CI 13.2-24.9) (P = .113) during the 5-year period.
      CONCLUSION: There was a significant increase in incontinence measured by pad test
      and leakage index 5 years after cessation of organized pelvic floor muscle
      exercise. However, 75% showed no leakage during stress test, and 70% were
      satisfied with the condition. Seventy percent were exercising the pelvic floor
      muscles at least once a week, and pelvic floor muscle strength was maintained.

PMID- 8559537
TI  - Prevention of postoperative urinary stress incontinence after surgery for
      genitourinary prolapse.
AB  - OBJECTIVE: To compare cystopexy alone versus cystopexy with posterior
      pubourethral ligaments plication for the occurrence of postoperative stress
      incontinence after prolapse surgery, and to compare the two surgical series in
      terms of complications and urodynamic effects. METHODS: One hundred two continent
      patients randomly underwent cystopexy alone (N = 52) or cystopexy with posterior
      pubourethral ligaments plication (N = 50). All had a urethrocystocele grade 2 or
      greater and a negative stress test with the prolapse repositioned. A full
      urodynamic investigation was repeated 6 months after surgery. RESULTS: Twelve
      (23%) and 14 (28%) patients (P = .73) required intermittent self-catheterization
      for 11.1 +/- 5.1 and 16.5 +/- 11.1 days, respectively (cystopexy alone versus
      cystopexy with posterior pubourethral ligaments plication, P = .002). Long
      lasting difficulties in voiding were present in zero and five (10%) patients (P =
      .02). One subject receiving posterior pubourethral ligaments plication underwent
      urethral dilation for complete urinary retention. At 1 year follow-up, four
      patients (8%) in each series developed postoperative stress incontinence (P =
      .62). Symptomatic detrusor instability complicated the postoperative course in
      one patient (2%) of each group. CONCLUSION: Cystopexy alone implied lower
      morbidity in terms of resumption of spontaneous voiding and long-lasting
      difficulties in voiding. The procedure could be recommended as an effective and
      safe treatment for continent patients with severe urethrocystocele. Additional
      plication of the posterior pubourethral ligaments did not seem superior to
      cystopexy alone in preventing the postoperative occurrence of stress
      incontinence.

PMID- 8559538
TI  - Diagnosis and management of serious urinary complications after major operative
      laparoscopy.
AB  - OBJECTIVE: To evaluate the incidence, diagnosis, and management of serious
      urinary complications after major operative laparoscopy. METHODS: For this
      retrospective study of 953 consecutive cases of major operative laparoscopy from
      January 1, 1990, to December 31, 1994, we reviewed incidence, method of
      diagnosis, and management of complications. Urinary complications included
      bladder injuries, urinary fistulas, and ureteral injuries. Major operative
      laparoscopic procedures included hysterectomy, adnexectomy, treatment of tubal
      pregnancy, ovarian cystectomy, and ablation-fulguration of severe endometriosis
      (stage IV). RESULTS: Serious urinary complications were found during or after
      operative laparoscopy in 15 of 953 patients (1.6%, 95% confidence interval [CI]
      0.8-2.4). Four ureteral injuries, three bladder fistulas, and eight bladder
      perforations were documented in this series. Eight cases of urinary complications
      were recognized during the original surgery (one ureteral injury and seven
      bladder injuries) and repaired at that time. Laparotomy or additional major
      surgery was performed in seven patients (three ureteral injuries, two bladder
      fistulas, and two bladder perforations). CONCLUSIONS: Serious urinary
      complications after major operative laparoscopy were discovered in 1.6% of
      patients. This incidence compares favorably to serious urinary complications
      after standard gynecologic surgery. Intraoperative recognition of these
      complications will likely avoid additional surgery.

PMID- 8559539
TI  - Magnetic resonance imaging of the levator ani with anatomic correlation.
AB  - OBJECTIVE: To define in women the anatomy of the levator ani muscle visible on
      magnetic resonance imaging (MRI) so these muscles can be studied in women with
      prolapse or incontinence. METHODS: Multiplanar T1- and T2-weighted MRI was
      obtained of two female pelvic cadaver specimens, ages 25 and 33. One specimen was
      hemisected, with half sectioned in the axial plane and the other half in the
      coronal plane. The other specimen was sectioned in the coronal plane. Anatomic
      cross sections of these specimens were correlated with the cadaver MRI and MRI of
      living patients. One sagittal and two axial series of anatomic sections not
      imaged were also used for comparison. RESULTS: Serial sagittal and axial MRI
      demonstrates the pubovisceralis ("pubococcygeus") muscle as it originates from
      the pubic bone, passes alongside the urethra, vagina, and rectum, and then dorsal
      to the anorectum. Its muscle bulk, attachment to the distal half of the vagina,
      and insertion between the internal and external anal sphincters can be seen on
      axial views. The origin of the iliococcygeus muscle at the arcus tendineus
      levator ani is seen in axial and coronal images. Coronal and sagittal images
      demonstrate the relative thickness and medial position of the pubovisceralis
      muscle compared with the thin, diaphragm-like lateral iliococcygeus muscle.
      CONCLUSION: Magnetic resonance imaging of the cadaver pelvis demonstrates the
      detailed anatomy of the levator ani muscle. This is an important precursor to
      future research of the structure, bulk, and orientation of the levator ani in
      living women with prolapse.

PMID- 8559540
TI  - Postmenopausal bartholin gland enlargement: a hospital-based cancer risk
      assessment.
AB  - OBJECTIVE: To assess the risk of Bartholin gland carcinoma in postmenopausal
      women. METHODS: A referral patient population from a tertiary care cancer center
      and a hospital-based regional tumor registry was used in a case-control and
      retrospective cohort study. We searched for data on any discharge diagnosis or
      procedures involving the Bartholin gland, including excision, cystectomy, or
      marsupialization, and pathology reports confirming cancer diagnoses from a
      hospital-based regional tumor registry and a tertiary hospital's medical records
      department and operating room log. RESULTS: A total of 284 patients were
      identified, 161 patients from the hospital-based tumor registry and 123 from the
      tertiary hospital data bases. Pathology reports from 104 of the 161 patients with
      vulvar cancer were available and revealed two primary adenocarcinomas in
      postmenopausal women, one squamous cell carcinoma of the Bartholin gland in a
      postmenopausal woman, and two squamous cell carcinomas of the Bartholin gland in
      premenopausal patients over a 24-year period. Based on local New York State
      Department of Health census data, the incidence of Bartholin gland carcinoma was
      0.023 per 100,000 woman-years in premenopausal women and 0.114 per 100,000 woman
      years in postmenopausal women (incidence rate ratio 5.01, 95% confidence interval
      [CI] 0.67-25.1). The overall incidence rate of squamous cell vulvar carcinoma was
      0.42 per 100,000 woman-years in premenopausal and 4.72 per 100,000 woman-years in
      postmenopausal women (odds ratio [OR] 11.55, 95% CI 7.82-17.14). The ratio of
      Bartholin gland cancer to other vulvar cancers was two per 37 in premenopausal
      women versus three per 124 in postmenopausal women (OR 2.3, 95% CI 0.39-17.9). Of
      thirteen postmenopausal patients (mean age 65.4 years) with Bartholin gland
      enlargement admitted to the tertiary care center, only four (30.8%) had
      excisions, whereas the remainder (69.2%) had drainage or marsupialization. None
      of the patients treated with drainage or marsupialization were listed
      subsequently in the tumor registry as developing Bartholin gland cancer during a
      median surveillance of 10.3 years (range 1.7-14.4). CONCLUSION: Bartholin gland
      cancer is exceedingly rare in all women, including postmenopausal women. We were
      unable to find evidence that would justify excision as the initial treatment of a
      Bartholin gland enlargement in postmenopausal women. Drainage and selective
      biopsy may be sufficient as initial management.

PMID- 8559541
TI  - The relationship of early follicular phase serum LH and pregnancy rates in women
      with regular menses.
AB  - OBJECTIVE: To investigate the relationship of early follicular phase serum LH
      levels and pregnancy rates in ovulatory women with regular menstrual cycles.
      METHODS: One hundred consecutive couples seeking help for infertility who had
      bilateral tubal patency, a minimum motile sperm-density-of 2.5 million/mL, and
      regular menstrual cycles were enrolled in the study. Baseline serum measurements
      of LH, FSH, and testosterone were obtained before treatment. Patients were
      treated with clomiphene citrate, human menopausal gonadotropin, or progesterone
      supplementation, as needed. Treatment continued for 6 months or until conception
      occurred. The 6-month pregnancy rates were correlated with baseline early
      follicular phase serum levels and age. RESULTS: The 6-month viable pregnancy
      rates did not decrease with an increase in baseline LH serum levels; they were
      50% if LH was 10 mIU/L or less, 15.3% if LH was 11-20 mIU/mL, and 71.4% if LH was
      more than 20 mIU/mL. The 16.7% pregnancy rate in women whose baseline FSH
      exceeded 25 mIU/mL was significantly lower than the 56.3% rate in women whose FSH
      was 25 mIU/mL or lower. The pregnancy rates also declined significantly with age.
      When we controlled for age, FSH did not have an independent effect on conception
      rates. CONCLUSION: Early follicular phase serum levels of LH were not associated
      with pregnancy rates in infertile ovulatory women who were treated with
      progesterone in the luteal phase when needed. However, early follicular levels of
      FSH and age at treatment were found to be related to pregnancy rates.

PMID- 8559542
TI  - Previous cesarean delivery and the risk of ectopic pregnancy.
AB  - OBJECTIVE: To determine whether previous cesarean delivery is an independent risk
      factor for ectopic pregnancy. METHODS: We analyzed data collected between October
      1988 and August 1990 from a case-control study of ectopic pregnancy among parous,
      black, non-Hispanic women, 18-44 years old, at a major metropolitan hospital in
      Georgia. Cases were 138 women with confirmed ectopic pregnancy; controls were 842
      women either seeking abortion or delivering an infant. Unconditional logistic
      regression was used to estimate the relative risk while controlling for the
      effects of potential confounders selected a priori. RESULTS: Adjusted for age,
      parity, marital status, history of pelvic inflammatory disease, infertility,
      douching, and smoking, the odds ratio was 0.6 (95% confidence interval 0.4-1.1),
      indicating no significant association. CONCLUSION: We found no evidence of an
      increased risk of ectopic pregnancy related to previous cesarean delivery.

PMID- 8559543
TI  - An ethically justified algorithm for offering, recommending, and performing
      cesarean delivery and its application in managed care practice.
AB  - When cesarean delivery is substantively supported and vaginal delivery is not
      supported in beneficence-based clinical judgment, the physician should offer and
      recommend only cesarean delivery. When both cesarean and vaginal delivery are
      substantively supported in beneficence-based clinical judgment, the physician
      should offer both, discuss any controversy, and make a recommendation. When
      cesarean delivery is substantively supported and vaginal delivery is more
      substantively supported in beneficence-based clinical judgment, the physician
      should offer both and recommend vaginal delivery. If cesarean delivery is not
      supported and vaginal delivery is substantively supported in beneficence-based
      clinical judgment, the physician should offer only vaginal delivery. When
      cesarean delivery is requested and well supported solely in autonomy-based
      clinical judgment, the physician should repeat the recommendation for vaginal
      delivery and either perform cesarean delivery or make a referral. Physicians may
      use this algorithm in negotiating managed care contracts.

PMID- 8559544
TI  - An inevitable dilemma: prenatal testing for mutations in the BRCA1 breast-ovarian
      cancer susceptibility gene.
AB  - The BRCA1 breast-ovarian cancer susceptibility gene was identified recently.
      Germline mutations in BRCA1 may be responsible for as many as 5% of breast and
      ovarian cancers. Inherited alterations confer up to a 94% risk of developing
      breast and/or ovarian cancer by age 70. With the discovery of BRCA1, there will
      be a heavy demand for genetic testing. Because of the large size of the gene and
      the distribution of reported mutations, scientists face considerable technical
      problems in developing widely available screening tests; clinicians will face
      even greater ethical problems in applying them. In the context of research
      programs, women with BRCA1 mutations are already being identified, and their
      physicians are confronted with a number of complex medical, ethical, legal, and
      social issues. Obstetricians will be faced with counseling parents regarding
      prenatal testing for specific BRCA1 mutations. Although it is difficult to
      formulate straightforward guidelines regarding prenatal BRCA1 testing, clinicians
      and health care providers must be familiar with the nuances of the debate so that
      these issues can be discussed wisely with patients. As with many ethically
      challenging problems in medicine, individual clinicians and their patients will
      have to work together to determine the course of action with which they are most
      comfortable. Although elective termination of a pregnancy with a germline
      mutation in BRCA1 is an option, experience with other adult-onset diseases
      suggests that only a minority of parents will choose this option.

PMID- 8559545
TI  - Cardiac output in normal pregnancy: a critical review.
AB  - OBJECTIVE: To review the literature about the effect of normal pregnancy on
      cardiac output, with special attention to study design, measurement technique,
      position of the subject, and parity. DATA SOURCES: For studies from the period
      1955-1987, we examined Cumulated Index Medicus (National Library of Medicine
      Cataloging in Publication. Chicago: American Medical Association). For studies
      from 1988 to May 1, 1994, we used Medline on Silver Platter (U.S. National
      Library of Medicine Silver Platter International, 1994). METHODS OF STUDY
      SELECTION: Thirty-three cross-sectional and 19 longitudinal studies on cardiac
      output measurement in normal pregnancy were retrieved and reviewed. Thirteen
      longitudinal studies were excluded from analysis because an unvalidated technique
      was used or because not all subjects were measured at each study interval. The
      six remaining studies of genuine longitudinal design with at least two
      measurements throughout pregnancy were used for the definitive analysis. The
      results of the cross-sectional studies were included only to demonstrate a trend.
      DATA EXTRACTION AND SYNTHESIS: By pooling data from cross-sectional studies, a
      tendency was shown toward a higher cardiac output in the second trimester
      compared with the first trimester, and a tendency toward lower cardiac output was
      found in the third trimester compared with the second trimester. After delivery,
      cardiac output was lower than at any time during pregnancy. Selected longitudinal
      studies showed that the rise in cardiac output occurred early in the first
      trimester, and a further rise occurred during the second trimester. During the
      third trimester, cardiac output rose, fell, or plateaued, irrespective of the
      method of measurement applied or conditions during measurement. CONCLUSIONS:
      Cardiac output during the third trimester was widely divergent among the studies
      and probably dependent on individual factors. The tendency to report cardiac
      output as averages negated these inter-individual differences.

PMID- 8559546
TI  - High cervical spinal cord injury in neonates delivered with forceps: report of 15
      cases.

PMID- 8559547
TI  - Can meconium in the amniotic fluid injure the fetal brain?

PMID- 8559548
TI  - The menopause and osteoporosis.
AB  - Osteoporosis is a disease of reduced skeletal mass and microarchitectural
      deterioration of the skeleton, resulting in an increased risk of fractures. With
      the aging of the population, the considerable financial and personal costs of
      osteoporosis will increase. The loss of ovarian hormone production in menopause
      is the major risk factor for osteoporosis, causing increased skeletal resorption
      and relatively decreased bone formation. Estrogen administration protects from
      the loss of bone mass and reduces the incidence of vertebral and hip fractures,
      although administration must be continuous for the beneficial effects to remain.
      These effects occur regardless of the route of administration or the concomitant
      use of a progestin. Alternatives to estrogen are currently in development,
      including calcitonin, bisphosphonates, and tissue-specific estrogen.

PMID- 8559549
TI  - Menopause and hormone replacement therapy: an overview.
AB  - This article presents an overview of the health changes that women face as they
      traverse menopause and the years beyond. It serves to link a series of individual
      articles, which follow it in this journal issue and relate to specific topics in
      these areas important to women's health. Indications, contraindications, and
      risks and benefits of hormone replacement therapy are reviewed in depth.
      Alternative therapies are discussed and the role of preventive health is
      stressed. It seems that the menopause can be a time of positive change for women,
      provided that they and their physicians understand and individualize their care.
      If there is a central theme to such management, it is the education and
      responsibility of both the patient and physician.

PMID- 8559550
TI  - Hormones, mood, and cognitive functioning in postmenopausal women.
AB  - Findings from basic neuroscience have provided information on the effects of
      estrogen on brain morphology and chemistry that explain how this sex steroid may
      influence brain function. The clinical literature shows that estrogen enhances
      mood and specific aspects of cognitive functioning in postmenopausal women. There
      is also evidence that estrogenic effects on various psychological functions are
      dissociable and specific. Although several recent epidemiologic case-control
      studies have suggested a protective effect of estrogen against Alzheimer disease,
      these findings need to be verified by prospective, controlled investigations.

PMID- 8559551
TI  - Estrogen: effects on the cardiovascular tree.
AB  - My objective is to review the current literature with respect to basic science
      aspects concerning the effects of both endogenous and exogenous sex steroids on
      the vascular system. For simplification in this complex, burgeoning field,
      generalizations are made and mechanisms are highlighted. Major landmark studies
      in the English language over the past 25 years are reviewed. Cardiovascular,
      endocrinologic, and gynecologic references are targeted. Investigations by
      leading authorities are emphasized with an intent to bridge clinical significance
      with in vitro studies, in vivo data (both animal and human), and current
      epidemiologic information. Study results indicate that atherosclerotic lesions
      can stabilize, and occlusion can regress. The combined effects of estrogen in
      preventing atherosclerosis and maintaining arterial tone and integrity indicate
      that the circulatory system is a major target for estrogen action. A number of
      direct and indirect effects of estrogen have been shown to be beneficial.

PMID- 8559552
TI  - The clinical aspects of estrogen and the cardiovascular system.
AB  - Extensive epidemiologic and postmortem studies have identified a link between
      menopause and cardiovascular disease. The relation is especially strong in
      surgically menopausal women who do not receive estrogen replacement. More than 30
      observational studies and one small randomized, controlled clinical trial have
      provided evidence that estrogen replacement reduces cardiovascular risk by
      approximately 50%. Four studies that used coronary arteriography to document the
      presence of coronary atherosclerosis have provided some of the most compelling
      evidence that estrogen replacement reduces cardiovascular risk in postmenopausal
      women. One study of survival in women undergoing coronary arteriography found
      that the greatest improvement in total mortality took place in those women with
      substantial coronary stenosis; less benefit was observed in those without
      disease. Angiographic studies have also confirmed the importance of high-density
      lipoprotein cholesterol in mediating the effect of estrogen and the beneficial
      effect of estrogen on endothelial function. Although the addition of progestins
      to estrogen attenuates estrogen's effect on high-density lipoprotein cholesterol,
      limited observational daa have suggested that the cardioprotective effect is not
      reduced.

PMID- 8559553
TI  - Postmenopausal hormone therapy and breast cancer.
AB  - Given the magnitude of the older female population, the possibility that
      postmenopausal hormone therapy is associated with an increased risk of breast
      cancer is an issue of great public and individual importance. Epidemiologic
      evidence indicates the possibility of a slightly increased risk of breast cancer
      associated with long durations of postmenopausal estrogen use. However, in a
      review of the literature, it is apparent that the epidemiologic data are
      contradictory and do not yield uniform and consistent results. It is further
      apparent that adding a progestin to a postmenopausal hormone program does not
      alter the findings compared with the use of estrogen alone. Reasons for this
      disagreement and lack of definitive evidence are detailed, and it is suggested
      that any impact of postmenopausal hormone therapy on the risk of breast cancer is
      unlikely to be great. Finally, the question of whether a woman who has had breast
      cancer should use postmenopausal hormones is addressed.

PMID- 8559554
TI  - Carbohydrate cytochemistry of the endothelium lining the splenic blood vessels in
      the rat.
AB  - In the endothelial cells lining the rat splenic blood vessels, neutral
      carbohydrates were studied by means of combined periodic acid-thiocarbohydrazide
      silver protein (PA-TCH-SP) and alpha-amylase digestion methods. In the
      endothelial cells lining the central and follicular arteries of the spleen, the
      neutral glycoconjugate-containing surface coat of the luminal plasma membrane and
      related pinocytotic invaginations and vesicles in the apical cytoplasm were
      strikingly distinguished, as compared with those in the cells lining the splenic
      sinuses. In contrast, cytoplasmic glycogen particles in the sinus endothelial
      cells were apparently larger in amount than those in the arteriolar endothelial
      cells. Such cytochemical variations of neutral carbohydrates with the arteriolar
      and venous vessels of the rat spleen were discussed with special reference to
      varying cytophysiological functions of the endothelial cells with the different
      segments of the splenic blood vessels.

PMID- 8559555
TI  - Descending projections from the paraventricular hypothalamic nucleus to the
      spinal cord: anterograde tracing study in the rat.
AB  - We investigated the direct projections from the paraventricular hypothalamic
      nucleus (PVH) to the spinal cord. When Phaseolus vulgaris leucoagglutinin (PHA-L)
      was injected into the PVH, labeled descending fibers were observed running
      bilaterally through three pathways. The first pathway ran into the dorsal
      longitudinal fasciculus and projected to the central gray matter, Edinger
      Westphal nucleus, pedunculopontine tegmental nucleus, nucleus of the locus
      ceruleus and parabrachial nucleus. The second and third pathways coursed through
      the medial forebrain bundle, ventral tegmental area, and ventral part of the
      medulla oblongata. At the medulla oblongata, the second pathway curved
      dorsolaterally and joined Rexed's lamina V of C1 after giving many projections to
      the nucleus ambiguus, nucleus of the solitary tract, dorsal motor nucleus of the
      vagus, and a few to the area postrema. The fibers descended through lamina V
      until C5, and coursed through lamina I from C6 to the upper coccygeal segments.
      They gave collateral projections to lamina I from the cervical through the upper
      coccygeal segments. The third pathway coursed laterally and descended through the
      lateral funiculus after giving projections to the lateral reticular nucleus and
      the marginal layer of the spinal trigeminal nucleus. These fibers gave off many
      projections to the intermediolateral cell column of the thoracic cord and the
      sacral parasympathetic nucleus. Lamina X received many projections from the
      fibers of the lateral funiculus at C5 through the b-segment of sacral spinal
      cord. These results indicate that the PVH may integrate directly with the
      medullary and spinal autonomic regulatory nuclei, including the vagus complex,
      sympathetic intermediolateral cell column, laminae I and X, and sacral
      parasympathetic nucleus.

PMID- 8559556
TI  - Distribution of taste buds on the epiglottis of the rat and house shrew, with
      special reference to air and food pathways.
AB  - We investigated the positioning of the epiglottis in the pharyngo-laryngeal
      region and the distribution of taste buds on the epiglottis in the rat and house
      shrew, animals which have different feeding habits. In the fixed samples of both
      species, when the mouth was closed or slightly opened, the epiglottis was found
      to protrude into the nasopharyngeal hiatus above the soft palate. But it
      retracted from its position when the mouth was widely opened. In omnivorous rats
      (n = 6), the mean number (mean density +/- s.d.) of taste buds was 52 (12.6 +/-
      2.2/mm2) on the laryngeal surface but only 4 (1.3 +/- 1.0/mm2) on the oral
      surface. The three-dimensional view was reconstructed from serial sections. The
      taste buds were distributed most densely close to the caudal base and became
      fewer toward the more rostral tip. In insectivorous house shrews (n = 2), 4 taste
      buds on average were found only on the laryngeal surface of the epiglottis.
      Epiglottal taste buds may work as chemosensory detectors to initiate the reflex
      reaction to protect the airway from oral substances during swallowing and
      drinking.

PMID- 8559557
TI  - Vagal preganglionic neurons innervating the different gastric regions in the
      Japanese quail (Coturnix japonica).
AB  - The cytoarchitecture and distribution patterns of the vagal preganglionic neurons
      within the dorsal motor nucleus of the vagus nerve (DMNX) innervating the
      proventriculus and the gizzard of the Japanese quail were examined by Nissl
      staining and the horseradish peroxidase (HRP) method. A 30% solution of HRP was
      injected into nine different gastric regions: the ventral and dorsal parts of the
      proventriculus, the caudodorsal and cranioventral thick muscles, the craniodorsal
      and caudoventral thin muscles, and the pylorus, and the ventral and dorsal
      tendons of the gizzard. Nissl preparations showed that the DMNX is composed of
      two cell groups, the dorsal magnocellular and mediocellular subnucleus (Xd) and
      the ventral parvicellular subnucleus (Xv). After injection of HRP into the
      ventral and dorsal parts of the proventriculus, HRP-labeled cells were
      predominantly observed in the left and right DMNX, respectively. The rostrocaudal
      distribution patterns of HRP-labeled cells in the Xd and Xv were symmetric on the
      left and right sides. The distribution patterns of labeled cells following the
      injection of HRP into each region of the gizzard showed that there was very
      little difference in the number of neurons between the left and right DMNX, and
      no topographic localization was found in the Xd and Xv. The vagal preganglionic
      neurons projecting to the gizzard lay more caudal than the ones for the
      proventriculus. This study suggested topographic localization in the distribution
      patterns of the vagal preganglionic neurons innervating the proventriculus and
      the gizzard.

PMID- 8559558
TI  - Classification of the ophthalmic artery that arises from the middle meningeal
      artery in Japanese adults.
AB  - In a study of Japanese adults, we found that the orbital branch (OB) passing
      through the superior orbital fissure frequently anastomosed with the lacrimal
      artery or the ophthalmic artery (12/20). However, the OB passing through the
      meningo-orbital foramen (mof) only associationaly anastomosed with branches of
      the ophthalmic artery (4/79). Furthermore, the OB in the orbit, excluding the
      lacrimal gland as previously reported. We examined 116 cases in which the OB
      passed through the mof in 129 adult Japanese cadavers (45.0% in 258 sides). The
      OB passing through the mof was always distributed to the periorbital region and
      the area that it supplied was limited to the periorbita in about half of those
      cases. In another half of the cases (58/116), the area supplied included the
      lacrimal gland.

PMID- 8559559
TI  - Microscopic anatomy of the equine skin with special reference to the dermis.
AB  - We have observed and re-evaluated the histology of the skin of the horse, using
      samples from four Thoroughbreds. The skin was composed of the usual three
      components: epidermis, dermis and subcutis. In particular, the dermis was found
      to have three fibrous components: a papillary layer, a reticular layer and a
      cordovan-leather tissue layer. The cordovan-leather tissue layer was subdivided
      into a superficial main layer and a deeper accessory layer. The superficial main
      layer was thick, and present in all of the skin samples. The deeper accessory
      layer was found in the dorsal and dorso-lateral parts of the neck and trunk and
      in the extremities. Hair bulbs and sudoriferous glands did not extend into the
      cordovan-leather tissue layer and subcutis.

PMID- 8559560
TI  - Architecture of the lateral line organ of the sea eel Conger myriaster.
AB  - The architecture of trunk canal neuromasts of the Japanese sea eel was
      morphologically examined. A fluid-filled canal is connected with the outside by
      horn-shaped tubules whose outer openings are seen as pores, which are variable in
      shape and very narrow as compared to the canal diameter. A projection shaped like
      a semilunar valve hangs over each neuromast from the opposite wall. The total
      number of hair cells in a canal neuromast was 500 to 600, about fivefold more
      numerous than that in a superficial neuromast. Two groups of hair cells,
      rostrally and caudally oriented, are nearly equal in number. The observed
      architectures are thought to favor efficient detection of the flow of water
      within the canal. These findings substantiate the current understanding that each
      canal neuromast encodes the pressure difference between two adjacent pores.

PMID- 8559561
TI  - A qualitative ultrastructural study of melanocytes after grenz-ray and UVA
      irradiation.
AB  - Seven female human subjects were irradiated with 4 Gy of grenz rays and 30J/cm2
      of long-wave ultraviolet (UVA) radiation once a week for three weeks. 6/7
      subjects when irradiated on the back developed a clearly visible pigmentation due
      to both grenz-ray and UVA pigmentation. The effect on epidermal melanocytes was
      observed with transmission electron microscopy. Ultrastructural changes in
      melanocytes following both grenz-ray and UVA irradiation were an increase in the
      number of premature and mature melanosomes, elongation and protrusion of
      cytoplasm, sometimes indented nuclei, and the development of multilamella of
      basal lamina. Compared with UVA-irradiated skin, in the same individuals the
      melanocytes seemed somewhat more hypertrophic after grenz-ray irradiation. In
      general the observed qualitative ultrastructural differences between UVA- and
      grenz-ray-irradiated melanocytes were limited, indicating that the influence of
      grenz-rays is similar to that of UVA.

PMID- 8559562
TI  - Midbrain paralemniscal projections to the facial nucleus: an anatomical and
      immunohistochemical study.
AB  - Serial 30 microns-thick sections through the midbrain tegmentum were stained with
      cresyl violet. The PL was found to be situated along the medial edge of the
      lateral lemniscus. The PL consisted of small- (10-15 microns) and medium-sized
      neurons (25-35 microns), and was the most prominent at the caudal level of the
      superior colliculus. In order to confirm the existence of the inhibitory
      paralemniscal-facial pathway, a combined HRP and immunohistochemical technique
      was use in the rat. This experiment revealed that 10.9% of the total number of
      GABA immunoreactive PL neurons also labeled with HRP after HRP injection was made
      in the medial part of the facial nucleus (FN). Electron microscopic observations
      were carried out on the medial part of the facial nucleus (FN) after kainic acid
      injection was made into the contralateral PL in the cat. The majority of
      degenerating PL fibers were ranged from 0.5 to 3.1 microns in diameter and made
      synaptic contacts with somata, proximal dendrites and dendritic profiles. These
      fibers, containing either round or pleomorphic vesicles, formed asymmetrical or
      symmetrical synapses. It was of particular interest in the present study that
      40.7% of the total number of degenerating fibers make synaptic contacts with
      large dendrites more than 3.0 microns in diameter.

PMID- 8559563
TI  - The double omohyoid muscle in humans: report of one case and review of the
      literature.
AB  - An anomalous muscle was found in the right anterior cervical region of a 68-year
      old Japanese man. The muscle was investigated anatomically, with special
      reference to its supply. Few such reports are available. The anomalous muscle
      arose from the upper margin of the scapula as an aponeurotic sheet, ran
      medialocranialward and separated into the superficial and profound fasciculi at
      the lateral edge of the sternohyoid muscle. The former fasciculus was inserted
      into the lower border of the hyoid bone without fusing with adjacent muscles, or
      as an independent fasciculus. Meanwhile, the latter fasciculus incompletely fused
      with the lateral portion of the sternohyoid muscle. This muscle was supplied from
      its posterior surface and the upper edge by two slender nerves from the ansa
      cervicalis (roots of origin: C1, C2 and C3). Based on the nerve supply and a
      review of the literature, the muscle is discussed in terms of its true nature and
      its mechanism of formation. As a result of the investigation, this muscle is
      assumed to be a vestigial structure in humans reduced from the M. episterno
      cleido-hyoideus sublimis (Furbringer), which is observed in lower types of
      vertebrates (reptilies, etc.).

PMID- 8559564
TI  - Ultrastructure of spinal relay of hypoglossal afferents to the parabrachial
      nucleus.
AB  - Wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) injection into
      the hypoglossal nerve mainly resulted in retrograde labeling in the superior
      ganglia of the glossopharyngeal and vagal nerves ipsilaterally. Anterogradely
      labeled fibers were found in lamina I of the ipsilateral upper cervical spinal
      cord with a few distribution to laminae IV-V and VII-VIII. WGA-HRP injection into
      the PBN revealed intensive labeling of lamina I neurons of the upper cervical
      spinal cord ipsilaterally. These light microscopic observations appear to
      indicate the hypoglossal sensory inputs to the PBN through the spinal cord. In
      order to investigate the synaptic nature of this spinal relay, electron
      microscopic observations were carried out on lamina I of the first and second
      cervical spinal cord after cutting the hypoglossal nerve and WGA-HRP injection
      into the PBN in the same animal. The spinoparabrachial projection neurons were
      demonstrated to show a low cytoplasmic/nuclear ratio and have an oval or deeply
      indented nucleus with a centrally located nucleolus. Furthermore, dark and light
      type degenerating fibers were observed to make synaptic contacts with HRP-labeled
      somata and dendritic profiles.

PMID- 8559566
TI  - [Franz Cardinal Konig: "We always had those great discussions...". Interview by
      Harald Verworner].

PMID- 8559565
TI  - [In the middle ages nursing was ... a purely religious enterprise].

PMID- 8559567
TI  - [Hauling stones or bearing crosses. Disease and the anointing of patients in a
      christian hospital].

PMID- 8559568
TI  - [Nursing and foreign cultures: Islam].

PMID- 8559569
TI  - Irradiated soft tissue and its management.
AB  - The healing of a surgical wound is significantly affected by radiation. Radiation
      can affect all cells within its treatment field, thus making irradiated tissue
      more susceptible to trauma, infection, and irritation. In the irradiated patient,
      careful preoperative planning and a preventive approach to optimize conditions
      for wound healing are crucial to minimizing complications. This article describes
      the principles and management of common complications seen from irradiated soft
      tissue wounds of the head and neck.

PMID- 8559570
TI  - Irradiated bone and its management.
AB  - There are two undeniable attributes of radiotherapy: its value in controlling
      head and neck malignancies and the progressive damage it inflicts on all treated
      tissues. It is fortunate that over the past decade, we have developed techniques
      and treatments that counteract, at least in part, the negative effects of
      radiotherapy on bone. Some of these measures are purely preventive and must be
      employed before or during radiation therapy to be successful. They include
      limiting the total radiation dose to less than 7000 Rads, appropriately shielding
      structures that do not require radiation, sparing one or more major salivary
      glands to minimize xerostomia, limiting fraction dosages to less than 200 Rads,
      obtaining pre-radiation dental evaluations, and performing dental extractions
      before radiotherapy begins. Additionally, treatments have been devised to prevent
      ORN following radiotherapy. They consist of patient participation in aggressive
      dental maintenance programs, oral fluoride treatments, and the use of
      preextraction hyperbaric oxygen when unhealthy teeth need to be removed. Should
      radiation-induced complications develop in spite of these efforts, treatments
      have been developed that effectively deal with ORN, namely, hyperbaric oxygen
      (the Marx protocol) and prolonged courses of intravenous antibiotics. Finally,
      when ORN results in mandibular loss and deformity, these defects can be
      effectively reconstructed with either corticocancellous particulate bone grafts
      or microvascular osseous tissue transfers, depending on the clinical situation.
      Much can be done to prevent and treat radiation-induced complications involving
      bone, and it remains the responsibility of the head and neck surgeon to make sure
      that these measures are utilized. When all priorities in treating ORN are
      considered, differentiating a radiation-induced wound healing problem from a
      delayed tumor recurrence remains paramount. This differentiation should always be
      the first step in the treatment of any radiation-induced wound.

PMID- 8559571
TI  - Burns and wound management.
AB  - The evaluation and treatment of head and neck burns remains a challenge to the
      burn surgeon, because of the long-term emotional and psychologic effects of even
      the most minor change in facial appearance. Fortunately, the results currently
      achieved are orders of magnitude better than previously available, but they still
      remain far below the perfect outcome desired by both the physician and the burn
      victim.

PMID- 8559572
TI  - Management of scar contractures, hypertrophic scars, and keloids.
AB  - Aberrant fibrous tissue formation after surgery or trauma still presents a
      challenge to surgeons. Current research hopes to identify the characteristics of
      the population of fibroblasts that lead to hypertrophic or keloid scar formation.
      Surgical procedures and laser therapy followed by intralesional steroid
      treatments still are the foundation of treatment; but new modalities are being
      applied. The pathogenesis and management of hypertrophic scars, keloids, and scar
      contractures are discussed in this article.

PMID- 8559573
TI  - Methods and materials for wound closure.
AB  - Over the years, a number of different modalities have become available to close
      wounds. Before selecting a method of wound closure, the characteristics of the
      specific tissues to be closed and the anticipated time for wound healing to occur
      must be considered. This article reviews the methods available for tissue closure
      for the head and neck surgeon.

PMID- 8559574
TI  - Choice of wound dressings and ointments.
AB  - Over the last several decades, methods for wound dressing have dramatically
      changed. This article reviews the effects of wound dressing, antiseptics, and
      antimicrobials on the process of wound healing and on the incidence of wound
      infection. A set of guidelines is provided to help the surgeon decide what to
      apply topically to wounds and which dressing to select to achieve the best
      possible outcome in wound healing.

PMID- 8559575
TI  - Cutaneous wound healing. An overview.
AB  - This article is a general discussion of the mechanisms of soft-tissue wound
      healing with an emphasis on tissue. The overall phases of cutaneous wound healing
      and their influencing factors are described as are concepts for managing skin
      incisions to achieve a more optimal scar appearance.

PMID- 8559576
TI  - Cartilage wound healing. An overview.
AB  - Cartilage wound healing is a tentative balance between deposition of type I
      collagen in the form of scar tissue and repair by expression of type II collagen
      and proteoglycans. Small full-thickness cartilage defects are replaced by
      fibrocartilage, whereas partial-thickness defects are normally repaired by
      deposition of fibrous scar tissue. The mechanism of fibrocartilaginous repair
      appears to be mediated by proliferation and differentiation of mesenchymal cells
      of the marrow. Biologic grafts such as perichondrium have been successfully used
      to repair full-thickness defects, probably because they contain progenitor cells
      that can differentiate into chondroblasts. Other grafts composed of
      fibrocartilage, such as meniscus, appear potentially useful because they serve as
      a source for chondrocytes. When graft material is unavailable or cannot be easily
      fashioned to fit the defect, cell-cultured materials containing chondrocytes or
      progenitor cells appear promising. Finally, growth factors such as somatomedin-C
      have growth-promoting effect on cartilage and offer a future means of promoting
      cartilage repair.

PMID- 8559577
TI  - Facial bone wound healing. An overview.
AB  - Facial bone wound healing has practical importance not only in acute fracture
      repair, but also in head and neck surgery. Fundamental principles of fracture
      fixation are now understood, and the benefit of acute bone grafting has emerged.
      In the future, bone healing may be augmented with growth factors and implants
      incorporating cells grown in tissue culture.

PMID- 8559578
TI  - Nerve wound healing. An overview.
AB  - This article describes the mechanisms of peripheral nerve healing and the efforts
      to achieve an optimal healing outcome. The mainstay of treatment has been
      adherence to good surgical technique and the use of microsurgical equipment.
      Despite advances in microsurgery, complete structural and functional recovery is
      uncommon. Research focused on adjunctive methods for nerve repair is also
      reviewed in this article.

PMID- 8559579
TI  - Respiratory mucosa wound healing and its management. An overview.
AB  - Successful management of airway wounds are gauged by the extent to which the
      three functions of the airway (protection, respiration, phonation) are preserved.
      A major objective during wound healing of the airway is to minimize scarring and
      stricture formation. This article discusses the important concepts relating to
      current management strategies of the airway and encourages future directions of
      research.

PMID- 8559580
TI  - Tympanic membrane wound healing. An overview.
AB  - This article is a comprehensive overview of tympanic membrane injury and its
      healing. Its wound healing process is unique from soft tissue because
      epithelialization occurs before fibrous tissue advancement. Contemporary and
      future modalities to improve tympanic membrane repair are also discussed in this
      article.

PMID- 8559581
TI  - Growth factors in wound healing.
AB  - Growth factors are signal proteins that regulate the cellular processes in wound
      healing. By manipulating the actions of growth factors, it may be possible to
      accelerate or modify wound healing. Currently, intense research is being
      conducted throughout the world to investigate this possibility. In
      otolaryngology, the impact of improved wound healing could be tremendous. This
      article discusses the involvement of growth factors in soft-tissue healing that
      is relevant to otolaryngology.

PMID- 8559582
TI  - Immune involvement in wound healing.
AB  - Both in vitro and in vivo studies have demonstrated that the presence of both
      macrophages and T lymphocytes at the wound site is essential in order for the
      normal healing process to occur. Both macrophages and T lymphocytes possess the
      capacity to regulate essential steps in the process of wound healing. The
      presence of macrophages is essential for the initiation and maintenance of wound
      fibroblast activity. T cells do not appear to be required for the initiation of
      the healing process, and healing can progress in the absence of T lymphocytes,
      but the presence of an intact T-cell immune system is essential for a normal
      outcome, indicating that the T cells probably exert a regulatory influence over
      macrophage-induced activities. Further research is still required into the
      interaction of these immune cells, their secretory products, and other wound
      elements before our understanding of the mechanism of wound healing is complete.

PMID- 8559583
TI  - Wound healing after laser surgery.
AB  - Compared with scalpel wounds, CO2 laser wounds show delays in inflammation,
      collagen production, reepithelialization, and tensile strength in the early
      stages of healing. Some of these delays are similar to those seen with
      electrocautery and burn wounds. Later stages compensate for these early
      deficiencies, because scalpel and laser wounds become more similar in
      epithelialization and wound strength over time. Healed CO2 laser wounds tend to
      have less scar contraction than scalpel wounds. Debridement of initial laser
      wound char, tissue cooling techniques during lasering, and pulsed modes of laser
      delivery all seem to result in more rapid, favorable healing. Similar wound
      healing trends have been seen with the CO2 laser in bone, with other lasers, and
      with laser vascular and neural anastomosis. Biostimulation with low-level laser
      energy is a complex subject of ongoing investigations.

PMID- 8559584
TI  - The infected wound and its management.
AB  - The infected wound is one of the most frequent causes of delayed wound healing.
      Even in the face of appropriate antibiotic prophylaxis, infections can occur in
      10% to 20% of clean-contaminated procedures in the head and neck. The authors
      describe their comprehensive approach to prevent and manage the infected wound at
      the head and neck area.

PMID- 8559585
TI  - The impact of variations in temperature on early Plasmodium falciparum
      development in Anopheles stephensi.
AB  - The effect of temperature on early Plasmodium falciparum development was examined
      in Anopheles stephensi. The rates of both ookinete development and bloodmeal
      digestion were lengthened as temperatures decreased from 27 to 21 degrees C.
      However, low temperatures (21-27 degrees C) did not significantly influence
      infection rates or densities of either ookinetes or oocytes. In contrast, high
      temperatures (30 and 32 degrees C) significantly impacted parasite densities and
      infection rates by interfering with developmental processes occurring between
      parasite fertilization and ookinete formation, especially during zygote and early
      ookinete maturation. This study demonstrates clearly that temperature affects the
      sporogonic development of P. falciparum in anophelines by altering the kinetics
      of ookinete maturation. These studies not only confirm the ookinete as the key
      development stage affecting the probability of vector infectivity, they provide
      new insights into the epidemiology of P. falciparum infections.

PMID- 8559586
TI  - The blood-stages of Plasmodium georgesi, P. gonderi and P. petersi: course of
      untreated infection in their natural hosts and additional morphological
      distinctive features.
AB  - In the blood of a Cercocebus albigena and of a C. galeritus agilis monkey, the
      infection with Plasmodium gonderi was found to follow its well-known chronic
      course; P. georgesi seemed to occur as a relapsing type of malaria parasite; P.
      petersi was found for only a few days and at a low level in C. albigena (end of
      an attack?). As shown by using polarized light, the pigment granules appeared
      mostly as fine dots in P. georgesi, short rods in P. gonderi and long needles in
      P. petersi. The three species can be distinguished by the morphological
      appearance of the nucleus of the young trophozoites, and also by the measurement
      of its surface area (Sa): small round nucleus (Sa = 0.81 +/- 0.06 microns 2) in
      P. gonderi, large 2-coloured nucleus (Sa = 1.43 +/- 0.21 microns 2) in P.
      petersi, and long crescent-shaped nucleus (Sa = 2.18 +/- 0.25 microns 2) in P.
      georgesi. The first colour illustrations of the blood-stages of P. georgesi are
      presented. The dynamics of single and mixed blood infections in primate malaria
      parasites are discussed, with a proposal to classify them into 3 types.

PMID- 8559587
TI  - Plasmodium yoelii nigeriensis: the effect of high and low intensity of infection
      upon the egg production and bloodmeal size of Anopheles stephensi during three
      gonotrophic cycles.
AB  - Anopheles stephensi mosquitoes showed a reduction in fecundity over 3 successive
      gonotrophic cycles, after becoming infected with Plasmodium yoelii nigeriensis.
      This effect could be observed at high oocyst burdens (> 75) or at low oocyst
      burdens (mean of 4.36). Mean bloodmeal size of the infected mosquitoes was
      significantly reduced only when feeding upon a mouse with a high gametocytaemia
      and the conversion of the bloodmeal into eggs by the infected mosquitoes was
      disrupted. Patterns of infected mosquito mortality, over the 3 gonotrophic
      cycles, varied with severity of infection. Although in 1 case increased mortality
      and decreased bloodmeal size may have affected fecundity, this could not have
      accounted for all of the observed fecundity reduction. We propose that other,
      unknown parasite related factors, are involved.

PMID- 8559588
TI  - Characterization of the first European isolate of Neospora caninum (Dubey,
      Carpenter, Speer, Topper and Uggla).
AB  - Neospora caninum is an apicomplexan, protozoan parasite, which causes severe
      disease in dogs and cattle. It has previously been isolated only in the United
      States. A 5-week-old Boxer pup with a progressive hindlimb paresis was diagnosed
      as suffering from neosporosis on the basis of clinical signs and the presence of
      anti-Neospora antibodies in it, 2 litter-mates and its dam. Despite treatment
      with sulphonamides, the pup was euthanased 3 days later. The diagnosis of
      neosporosis was confirmed by immunohistochemical examination of muscle and CNS
      tissue sections from the pup. Parasites were isolated into Vero cell culture from
      the cerebrum, and confirmed as Neospora caninum by immunofluorescence with
      specific antibody, tachyzoite ultrastructure and 16S-like ribosomal RNA
      sequences. This isolate (designated NC-Liverpool) has been continuously passaged
      every 7-10 days. Its growth characteristics, ultrastructure and antigenic
      profile, as revealed by immunoblotting, have revealed no major differences from
      the American NC-1 isolate. Furthermore, no difference was seen when comparing the
      sequences of 16S-like ribosomal RNA and the ITS1 region of the two isolates.

PMID- 8559589
TI  - Spontaneous release of cysteine proteinases but not of pore-forming peptides by
      viable Entamoeba histolytica.
AB  - Invasive properties of pathogenic Entamoeba histolytica have been postulated to
      depend on the secretion or release of cysteine proteinases and pore-forming
      peptides (amoebapores) by trophozoites. To establish whether such toxic molecules
      are released by viable trophozoites or upon cellular disintegration, amoebae were
      maintained in various culture media, and activities in supernatants were
      monitored over time in correlation to cellular integrity. By measuring the
      release of the cytoplasmic marker enzyme NADP(+)-alcohol dehydrogenase, it became
      apparent that release of amoebapore was accompanied by cellular disintegration.
      In contrast, considerable quantities of cysteine proteinases were found to be
      present in culture supernatants also when amoebae remained intact. Treatment of
      amoebae with concanavalin A, bacterial lipopolysaccharides or the calcium
      ionophore A23187 did not result in amoebapore secretion suggesting that here
      target cell contact is required as an essential stimulus.

PMID- 8559590
TI  - Asparaginyl endopeptidase activity in adult Schistosoma mansoni.
AB  - Sequence comparisons have recently shown that the Schistosoma mansoni protein
      Sm32 is similar to asparaginyl endoproteinases, a novel family of cysteine
      proteinases, of which the legumains from legumes are the best characterized. By
      synthesizing and employing fluorogenic peptide substrates for the specific
      detection of asparaginyl endopeptidases, we have identified this type of activity
      in extracts of adult S. mansoni. The S. mansoni activity is similar to that of
      the legumains in its substrate specificity and sensitivity to thiol inhibitors,
      but differs in its pH and temperature optima for activity. In contrast, unlike
      the legumains, the schistosome asparaginyl endopeptidase activity is not
      activated by the reducing agent dithiothreitol. As suggested for legumains, Sm32
      may function in the post-translational modification processes that regulate the
      activity of other molecules.

PMID- 8559591
TI  - Improved specificity of Trypanosoma cruzi identification by polymerase chain
      reaction using an oligonucleotide derived from the amino-terminal sequence of a
      Tc24 protein.
AB  - In the present study, the diagnostic value of Trypanosoma cruzi recombinant
      protein (Tc24) was examined. Although antibodies against Tc24 were detected
      during natural and experimental T. cruzi infections, specificity studies revealed
      that sera from T. rangeli-infected mice also recognized to some extent Tc24
      protein. In addition, sera from Tc24-immunized mice reacted against a 21 kDa
      polypeptide in T. rangeli extracts. Detailed analysis of the antibody response
      against 20-40 peptide localized in the Tc24 amino-terminal domain suggests that
      this sequence is not expressed by T. rangeli 21 kDa antigen. Therefore, the PCR
      reaction using oligonucleotides corresponding to a 20-26 peptide clearly
      demonstrated the specificity of the oligoprobes for T. cruzi identification.
      Positive signals were also found when using blood samples from T. cruzi-infected
      mice. Taken together, these results suggest that the PCR-based 20-26 assay may be
      useful in the specific diagnosis of Chagas' disease.

PMID- 8559592
TI  - Hymenolepis diminuta and H. microstoma: uptake of cyclosporin A and drug binding
      to parasite cyclophilins.
AB  - Cyclosporin A (CsA) acts as a powerful immunosuppressant through its binding to
      the cytosolic isomerase, cyclophilin (CyP), forming a complex which inhibits the
      phosphatase activity of calcineurin. The drug is also selectively anti-parasitic
      but its mode of action remains unknown. The mouse tapeworm, Hymenolepis
      microstoma is sensitive to CsA, but the rat tapeworm, H. diminuta is not
      susceptible either in rats, mice or in vitro. Using these two tapeworm models,
      the uptake and binding of CsA were examined in relation to parasite cyclophilins.
      Uptake and compartmentalization of the drug were markedly different in the two
      species: H. microstoma takes up more drug than does H. diminuta and sequesters
      more drug into intracellular compartments. Characterization of cyclophilins using
      both CsA binding and isomerase activity assays reveals that H. microstoma
      possesses two cyclophilin isoforms (M(r) 17,700 and 21,400) with isomerase
      activity that is inhibited by CsA. using identical assays, we have been unable to
      demonstrate CsA-binding proteins or CsA-sensitive isomerase activity in H.
      diminuta. These data suggest that the anthelmintic action of CsA relates in some
      way to the presence and function of parasite cyclophilins.

PMID- 8559593
TI  - Identification and properties of a neuropeptide-degrading endopeptidase
      (neprilysin) of Ascaris suum muscle.
AB  - We have previously identified in membranes of the locomotory muscle of Ascaris
      suum a phosphoramidon-sensitive endopeptidase which hydrolyses the neuropeptide
      AF1 (Lys-Asn-Glu-Phe-Ile-Arg-Phe-NH2) by cleavage of the Glu3-Phe4 bond (Sajid &
      Isaac, 1994). We have determined the properties of this neuropeptide-degrading
      enzyme of A. suum muscle using AKH-1 (pGlu-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr
      NH2) and [D-Ala2, Leu5]enkephalin as convenient endopeptidase substrates.
      Phosphoramidon, thiorphan and SQ 28603, potent inhibitors of mammalian neprilysin
      (neutral endopeptidase, endopeptidase 24.11), inhibited the endopeptidase
      activity towards AKH-I with IC50 values of 0.13 microM, 22 microM and 6.3 microM,
      respectively. Two other neprilysin inhibitors (SCH 32615 and SCH 39370) and the
      bivalent metal ion chelators, EDTA (1 mM) and 1, 10 bis-phenanthroline (1 mM)
      failed to inhibit the nematode enzyme. The endopeptidase had a neutral pH optimum
      and a significant proportion (45%) of the enzyme activity partitioned into the
      detergent-rich phase of Triton X-114, indicating that the enzyme is an integral
      membrane protein. The muscle enzyme also attacked [D-Ala2, Leu5]enkephalin
      cleaving the Gly3-Phe4 bond and this hydrolytic activity was inhibited by
      phosphoramidon and thiorphan (IC50, 0.28 microM and 15.8 microM, respectively)
      but not by EDTA and 1, 10 bis-phenanthroline. The phosphoramidon-sensitive
      endopeptidase activity was detected on intact muscle cells prepared by
      collagenase treatment of the body wall musculature, indicating that endopeptidase
      is accessible to peptide molecules that interact with the cell surface.

PMID- 8559594
TI  - Nuclear rDNA ITS sequence variation in the trematode genus Echinostoma: an aid to
      establishing relationships within the 37-collar-spine group.
AB  - The taxonomic history of members of the 37-collar-spine group within the genus.
      Echinostoma has been very confused. We obtained DNA sequence data from the
      nuclear rDNA ITS1, 5.8S and ITS2 of 7 nominal species belonging to this group,
      Echinostoma trivolvis (Cort, 1914), E. revolutum (Frolich, 1802), E. caproni
      Richard, 1964, E. liei Jeyarasasingam et al. 1972, E. paransei Lie & Basch, 1967,
      two African isolates, E. sp.I and E. sp.II, and of one 28-collar-spined
      echinostome, E. hortense (Asada, 1926). Five of the eight species were clearly
      distinguishable using ITS data. Sequences from the remaining three taxa, E.
      caproni, E. sp.II and E. liei were identical to one another and the group
      containing these taxa was distant from other 37-collar-spine species on a
      phylogenetic tree. E. trivolvis and E. paraensei form a second, but less distinct
      group within the 37-collar-spine group. The resolution obtained using DNA
      sequencing will assist in the current reclassification of the group. It also
      provides a model for future work on sibling species.

PMID- 8559595
TI  - Estimating the number of multiple-species geohelminth infections in human
      communities.
AB  - Infections with Ascaris lumbricoides, Trichuris trichiura and the hookworm
      species are often found in the same communities and individuals. Hosts infected
      by more than one species are potentially at risk of morbidity associated with
      each infection. This paper describes the use of a probabilistic model to predict
      the prevalence of multiple-species infections in communities for which only
      overall prevalence data exist. The model is tested against field data, using log
      linear analysis, and is found to be more effective at estimating the numbers of
      multiple infections involving hookworms than those involving only A. lumbicoides
      and T. trichiura. This latter combination of infections is found, in half the
      communities examined, to be more common than expected by chance. An age
      stratified analysis reveals that the degree of interaction between these two
      infections does not alter significantly with age in the child age classes of a
      Malaysian population.

PMID- 8559596
TI  - X-linked lymphoproliferative disease: twenty-five years after the discovery.
AB  - The X-linked lymphoproliferative disease (XLP), one of six described X-linked
      immunodeficiencies, stems from a mutation at Xq25 which renders males impotent to
      mount an effective immune response to the ubiquitous EBV. Purtilo, who first
      observed this disease in 1969, established a Registry in 1980 to serve as a
      worldwide resource for the diagnosis, treatment, and research of this condition.
      Since Purtilo's death in late 1992, the Registry and research unit have not only
      continued to function as a worldwide consultative service, but have contributed
      the following. First, the number of affected boys has continued to grow; some 272
      among 80 kindreds have been identified. Second, some boys (10%) who inherit the
      mutated XLP gene are immunologically abnormal even before evidence of EBV
      exposure. Third, the search for the XLP gene has been narrowed to a small region
      on Xq25. Its identification is near at hand; once cloned, this gene may well
      illustrate how the body orchestrates the complex immune response to EBV. Therein
      lies the justification for the quest for this gene, not only for the benefit of
      the few surviving boys and those to be born to female carriers, but also for
      defining its role in defending the body against a ubiquitous DNA virus.

PMID- 8559597
TI  - Glucocorticoid stimulation interacts with sympathetic innervation to affect
      cardiac development in oculo.
AB  - The effects of chronic glucocorticoid stimulation and sympathetic innervation on
      myocardium developing in the absence of hemodynamic load were tested by grafting
      embryonic rat hearts into the anterior eye chamber (in oculo) of adult host rats.
      Myocardial grafts in control rats with normal hormonal milieu were compared with
      grafts in rats with chronic glucocorticoid stimulation (dexamethasone 40
      micrograms/d) or glucocorticoid receptor type II blockade (RU 38486, 330
      micrograms/d). Unilateral superior cervical ganglionectomy of one eye chamber
      prevented sympathetic innervation to one graft in each host. Two indices of
      growth, graft size (projected area) and terminal graft weight, were obtained.
      Dexamethasone treatment increased both size and weight of sympathetically
      innervated grafts, whereas RU486 treatment significantly decreased graft weight.
      Conversely, dexamethasone treatment decreased graft size in denervated eye
      chambers, whereas RU486 treatment had no effect. No differences in graft beating
      rate were observed among conditions. Sympathetic innervation modulated the effect
      of glucocorticoids on developing myocardium, suggesting that growth of
      sympathetically innervated myocardium is enhanced with glucocorticoid exposure,
      but growth of noninnervated myocardium (e.g. fetal heart) may be compromised by
      excessive glucocorticoid exposure.

PMID- 8559598
TI  - Int-2 influences the development of the nodose ganglion.
AB  - The int-2 gene was first described as a common proviral integration site in
      tumors induced by mouse mammary tumor virus (MMTV). During embryonic development
      int-2 is produced and released by cells in the rhombencephalon and diffuses to
      the ectoderm to induce formation of the otocyst from the otic placode. Int-2 also
      influences the development of the vestibulocochlear ganglion that is derived from
      the otic placode. During embryogenesis the otic and nodose placodes, primordia of
      the inner ear and the nodose ganglia, respectively, are located adjacent to each
      other in the embryonic ectoderm. The nodose ganglia provide sensory innervation
      to all of the viscera. Using Northern analysis we determined that a high level of
      int-2 is transcribed in stage 14 chick embryos. This is the time when cells begin
      to migrate from the nodose placodes to form the nodose ganglia. Using human and
      mouse sequences to design primers around the translation start site of the
      transcript, a partial clone containing the translation start site of chick int-2
      was obtained by polymerase chain reaction amplification from chick genomic DNA
      and cloned. An antisense oligodeoxynucleotide was designed to the region of the
      translation start site, and in vitro and in vivo techniques were used to
      demonstrate that inhibition of int-2 translation using this antisense
      oligonucleotide causes delayed and abnormal development of the nodose placodes.
      For in vitro studies, explants of stage 12 chick embryos containing neural tube,
      adjacent surface ectoderm, and pharyngeal endoderm were cultured with int-2
      antisense oligonucleotide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559599
TI  - Maturation modulates serotonin- and potassium-induced calcium-45 uptake in ovine
      carotid and cerebral arteries.
AB  - Neonatal vulnerability to intracranial hemorrhage is often attributed to a
      relative inability of immature cerebral arteries to contract. Because this
      depressed contractility may involve age-related differences in cerebrovascular
      calcium handling, the present study examined age-related differences in cerebral
      artery contractility and its dependence on extracellular calcium from 24 newborn
      lambs and 36 adult sheep. Contractile tensions and 45Ca uptakes were measured
      under baseline conditions and as a function of time during stimulation by both
      receptor-dependent (100 microM serotonin) and receptor-independent (122 mM K+)
      mechanisms of contraction in endothelium denuded newborn (N) and adult (A) ovine
      middle cerebral (MCA) and common carotid (COM) arteries. Maximum contractile
      responses to potassium averaged 4.5 +/- 0.2 (N-COM), 5.8 +/- 0.9 (A-COM), 3.0 +/-
      1.1 (N-MCA), and 3.1 +/- 0.6 (A-MCA) g. Corresponding averages for responses to
      serotonin were 7.2 +/- 0.8, 7.3 +/- 1.1, 3.6 +/- 0.1, and 3.6 +/- 0.2; except for
      COM responses to potassium, contractile responses were little affected by
      maturation in either artery type. At baseline, uptakes averaged 0.39 +/- 0.04 (N
      MCA), 0.33 +/- 0.04 (A-MCA), 0.25 +/- 0.03 (N-COM), and 0.14 +/- 0.01 (A-COM)
      mumol Ca/g dry weight/min. Maximum increases in calcium uptake produced by
      potassium depolarization averaged 231 +/- 19% (N-MCA), 152 +/- 13% (A-MCA), 156
      +/- 11% (N-COM), and 140 +/- 14% (A-COM) above baseline. Corresponding increases
      produced by 100 microM serotonin averaged 201 +/- 15% (N-MCA), 129 +/- 23% (A
      MCA), 143 +/- 20% (N-COM), and 145 +/- 18% (A-COM).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8559600
TI  - Effect of Kawasaki disease on migration of human umbilical vein endothelial
      cells.
AB  - Kawasaki disease, which is characterized by systemic vasculitis causing coronary
      arterial involvement in childhood, shows a variety of immunoregulatory
      abnormalities. Especially the direct or indirect deleterious effects on
      endothelial cells of cytokines and anti-endothelial cell antibodies (AECA) are
      considered to be involved in the mechanism responsible for production of
      vasculitis. Intravenous administration of high doses of gamma-globulin (IVGG) has
      been used as an effective therapy for Kawasaki disease. To examine the behavior
      of endothelial cells affected by cytokines and IVGG in Kawasaki disease, we
      studied the effects of interferon (IFN), IL-1 beta, IL-6, and tumor necrosis
      factor (TNF)-alpha on the migration of human umbilical vein endothelial cell line
      (tHUE01) by a modified Boyden chamber method. Plasma from patients with acute
      Kawasaki disease markedly enhanced the migration of tHUE01 cells. Cytokines, with
      the exception of TNF-alpha, also enhanced the migration of tHUE01 cells in a dose
      dependent manner. Anti-IFN antibody inhibited the migratory activity in response
      to not only IFN-gamma but also to the plasma from patients with Kawasaki disease.
      Rabbit AECA (rAECA) also significantly stimulated the migration of tHUE01 cells.
      Plasma from patients treated with IVGG did not affect the migration of tHUE01
      cells. Addition of gamma-globulin significantly inhibited the migration of tHUE01
      cells induced by the cytokines or rAECA. These results suggest that cytokines and
      AECA are important in restructuring and destroying vessel walls in Kawasaki
      disease by enhancing the migration of endothelial cells, and that IVGG may be
      therapeutically effective for this disease by suppressing this endothelial cell
      migration.

PMID- 8559601
TI  - Differential regulation of glucocorticoid receptor expression by ligand in fetal
      rat lung cells.
AB  - The glucocorticoid receptor (GR) mediates glucocorticoid stimulation of
      surfactant production by fetal mammalian lung. In many other tissues,
      glucorticoids decrease expression of GR, thereby reducing responsiveness to these
      hormones. We therefore determined whether there is a similar effect of exogenous
      glucocorticoids on GR in fetal rat whole lung, and in the principal cell types
      involved in the stimulation of surfactant, the fibroblasts and the epithelial
      cells. The ontogeny of GR in late gestation lung differed between the two cell
      types, with maximal levels occurring in fibroblasts on gestational d 19, and on d
      20 in epithelial cells. Administration of dexamethasone (1 mg/kg) to the mother
      on gestational d 18 or 19 (term = 22 d) increased specific GR binding activity in
      whole lung 24 h later. Furthermore, in vitro, incubation of cultured fibroblasts
      of gestational d 20 with 10(-7) M cortisol increased GR immunoreactive protein
      and binding activity in a dose- and time-dependent manner, without affecting
      cellular levels of GR mRNA. However, identical treatment of d 20 distal airway
      epithelial cells was followed by decreased GR protein without significant change
      in cellular GR mRNA. Surfactant protein-A protein levels, taken as assessments of
      lung maturation, were increased in response to the same treatment. Our findings
      suggest that hormonal regulation of GR in fetal lung cells occurs at a
      posttranscriptional level, and is cell-specific. In the context of substantial
      increases in circulating glucocorticoid concentrations during late gestation,
      these findings may be of physiologic importance to the biochemical maturation of
      the antenatal lung.

PMID- 8559602
TI  - The combined effects of insulin and cortisol on surfactant protein mRNA levels.
AB  - Infants of diabetic mothers are frequently hyperinsulinemic and have an increased
      incidence of neonatal respiratory distress syndrome, a disease caused by a
      deficiency in the production of pulmonary surfactant by alveolar type II cells.
      It has been hypothesized that insulin inhibits fetal lung type II cell
      differentiation. We have shown previously that insulin inhibits the accumulation
      of surfactant protein (SP)-A and SP-B mRNA and has no effect on SP-C mRNA levels
      in human fetal lung tissue maintained in vitro. We hypothesized that treatment
      with glucocorticoids, which are used clinically to accelerate human fetal lung
      maturation, would overcome the inhibitory effects of insulin on human fetal lung
      development. In the present study, human fetal lung explants were maintained in
      the presence or absence of cortisol added alone, or in insulin plus cortisol
      added together. Cortisol significantly decreased SP-A mRNA levels by
      approximately 50% at the 100 nM concentration and significantly increased levels
      by approximately 20% at the 1 nM concentration. Cortisol increased SP-B and SP-C
      mRNA levels in a dose-dependent fashion (5- and 45-fold at 100 nM cortisol,
      respectively). The combination of 1 nM cortisol and insulin resulted in
      inhibition of mRNA levels for SP-A, SP-B, and SP-C at the high insulin
      concentrations (approximately 50% inhibition for SP-A and SP-B and approximately
      25% inhibition of SP-C mRNA levels, in the presence of 40 pmol/L x 10(-3)
      insulin). Surprisingly, 100 nM cortisol plus inhibitory concentrations of insulin
      increased SP-A mRNA levels (2-fold at 40 pmol/L x 10(-3).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8559603
TI  - Effect of weaning on serum lipoprotein(a) concentration: the STRIP baby study.
AB  - Risk for coronary heart disease is increased in adult Caucasians with high serum
      lipoprotein(a) [Lp(a)] concentration. In adults the concentration is mainly
      regulated by genetic factors. Our previous study suggests that breast milk has a
      beneficial effect on serum Lp(a) concentration in infants. Now we analyzed the
      influence of weaning by measuring serum Lp(a) and cholesterol in 414 infants at
      7, 13, 24, and 36 mo of age. At 7 mo the infants received, in addition to solid
      food, only breast milk (n = 148), breast milk and formula (n = 74), or formula
      only (n = 191). Median (range) serum Lp(a) concentrations were then 25 (< or = 12
      743) mg/L, 35 (< or = 12-1188) mg/L, and 45 (< or = 12-577) mg/L in the three
      feeding groups, respectively (p = 0.0013). Breast milk and formula were changed
      to cow's milk in all infants before 12 mo of age. At 13 mo serum Lp(a)
      concentration had increased more in infants who were weaned from breast milk than
      in those who had been fed both breast milk and formula, or formula only (median
      increases 37, 26, and 20 mg/L, respectively; p = 0.0062). Thus the serum Lp(a)
      concentration was similar in all feeding groups at 13 mo. This finding was also
      observed at 24 and 36 mo. The increase in serum Lp(a) concentration was
      independent of the baseline Lp(a) level, apolipoprotein E phenotype, gender, and
      weight gain of the infants between 7 and 13 mo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559604
TI  - Variability of continuously measured arterial pH and blood gas values in the near
      term fetal lamb.
AB  - In fetal sheep, arterial blood gas values show considerable spontaneous
      fluctuations. The aim of the present study was to obtain quantitative data on
      fetal blood gas variability. Accurate assessment of the intraindividual
      variations can hardly be obtained from intermittent blood samples, but requires
      continuous measurement. For this purpose we developed a small extracorporeal flow
      through cuvette, containing pH and blood gas electrodes and the fiber optic probe
      of an oximeter. The cuvette is connected through two catheters to the fetal
      circulation. Blood from the carotid artery flows through the cuvette at a
      constant rate of 2 mL/min and is drained into the jugular vein. Continuous
      recordings for 6 h were obtained from five chronically instrumented sheep fetuses
      at 134-137-d gestational age. Intraindividual variability of fetal arterial blood
      pH (pHa), partial pressure of arterial blood CO2 (Paco2) and O2 (Pao2), and
      saturation of arterial blood (Sao2) is quantitatively described. The individual
      variation coefficients ranged from 0.1 to 0.4% (pHa), from 1.4 to 7.6% (Paco2),
      from 2.5 to 5.5% (Pao2), and from 3.6 to 7.0% (Sao2). The 5th to 95 percentile
      intervals (delta) of the individual blood gas values ranged from 0.03 to 0.09
      (pHa), from 0.3 to 1.6 kPa (Paco2), from 0.22 to 0.5 kPa (Pao2), and from 10.5 to
      26.0% (Sao2). These findings indicate that considerable fluctuations in fetal
      arterial blood gases occur during a 6-h period. These fluctuations are associated
      with uterine contractures and changes in maternal and fetal activity.

PMID- 8559605
TI  - Changes in the temporal structure of periodic breathing with postnatal
      development in preterm infants.
AB  - The progressive decrease in the periodic cycle duration (PCD) of periodic
      breathing with postnatal age in term infants has been previously reported by a
      number of authors and is thought to be associated with peripheral chemoreceptor
      maturation. We hypothesized that a similar decrease should be observed in preterm
      infants. Therefore, in this study we measured the changes in PCD with postnatal
      age in a small group of preterm (n = 4) infants followed longitudinally (36
      afternoon nap studies) over the first 6 mo postnatally. PCD declined in these
      infants from 17.1 +/- 3.3 s (mean +/- 2 SD) at 9 d to 9.8 +/- 3.2 s (mean +/- 2
      SD) at 105 d. The regression slope was -0.072 s/d. Beyond 105 d there was no
      change in PCD up to 6 mo postnatally. We found no significant difference between
      active and quiet sleep. These results are similar to results previously published
      in term infants but apparently contradict recent data on a group of preterm
      infants. Possible reasons for this discrepancy are discussed. By examining long
      epochs of periodic breathing in these infants we also identified characteristic
      changes in PCD and V/A ratio, defined as the duration of the ventilatory period
      divided by the duration of the apneic interval. V/A ratio fell from the start of
      an epoch from 1.21 +/- 0.08 (mean +/- SEM) to a minimum of 0.62 +/- 0.03 and then
      increased again to 0.8 +/- 0.05 at the end of the epoch.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8559606
TI  - Blunted catecholamine responses after glucose ingestion in children with
      attention deficit disorder.
AB  - Eating simple sugars has been suggested as having adverse behavioral and
      cognitive effects in children with attention deficit disorder (ADD), but a
      physiologic mechanism has not been established. To address this issue, metabolic,
      hormonal, and cognitive responses to a standard oral glucose load (1.75 g/kg)
      were compared in 17 children with ADD and 11 control children. Baseline and oral
      glucose-stimulated plasma glucose and insulin levels were similar in both groups,
      including the nadir glucose level 3-5 h after oral glucose (3.5 +/- 0.2 mmol/L in
      ADD and 3.3 +/- 0.2 mmol/L in control children). The late glucose fall stimulated
      a rise in plasma epinephrine that was nearly 50% lower in ADD than in control
      children (1212 +/- 202 pmol/L versus 2228 +/- 436 pmol/L, p < 0.02). Plasma
      norepinephrine levels were also lower in ADD than in control children, whereas
      growth hormone and glucagon concentrations did not differ between the groups.
      Matching test scores were lower and reaction times faster in ADD than in control
      children before and after oral glucose, and both groups showed a deterioration on
      the continuous performance test in association with the late fall in glucose and
      rise in epinephrine. These data suggest that children with ADD have a general
      impairment of sympathetic activation involving adrenomedullary as well as well as
      central catecholamine regulation.

PMID- 8559607
TI  - Evaluation of the protective efficacy of reshaped human monoclonal antibody
      RSHZ19 against respiratory syncytial virus in cotton rats.
AB  - Reshaped human MAb RSHZ19, which is specific for the surface fusion protein of
      respiratory syncytial virus (RSV) is in clinical development for the prevention
      and treatment of RSV-induced disease in human infants. The current studies
      profile lung virus clearance and evaluate lung histopathology in MAb-treated, RSV
      infected cotton rats, a well characterized model of RSV infection. The highest
      dose of this MAb (10 mg/kg) administered parenterally 24 h before infection
      decreased subgroup A or B RSV lung titers to below detectable levels (> or = 2.3
      log10 reduction), and significantly reduced lung virus titers (> or = 2.0 log10
      reduction) when administered 96 h postinfection. Prophylactic administration of
      10 mg/kg RSHZ19 was significantly more protective than 1000 mg/kg conventional
      human immune serum globulin (HSIg), and protective serum-neutralizing titers in
      MAb-treated animals (1:32, which correlated with approximately 40 micrograms/ml
      determined by anti-idiotype ELISA) were significantly lower than those reported
      previously for HSIg or for convalescent human serum (1:200-1:400). MAb
      concentration in lung lavages was determined by ELISA to be approximately 1% of
      the serum MAb concentration, but was not detectable by neutralization assay. The
      degree of lung histopathology in MAb-treated cotton rats was proportional to lung
      virus titer, and inversely proportional to the RSHZ19 dose administered. There
      was no evidence of exacerbated disease in the lungs of MAb-treated animals. These
      studies thus support the potential clinical utility of RSHZ19 MAb in the
      prevention and treatment of RSV-induced disease in humans.

PMID- 8559608
TI  - Antibodies to tumor necrosis factor-alpha: use as adjunctive therapy in
      established group B streptococcal disease in newborn rats.
AB  - Group B Streptococcus (GBS) is the leading cause of neonatal sepsis. Adjunctive
      therapies are being sought to improve the outcome. Because increased blood levels
      of tumor necrosis factor (TNF)-alpha may play a role in the development of sepsis
      and an adverse outcome thereof, we evaluated the potential use of antibodies
      against TNF-alpha as adjunctive therapy of GBS sepsis. Using a neonatal rat model
      of GBS sepsis, we measured serum levels of TNF-alpha. Levels of TNF-alpha were
      significantly increased beginning 12 h after GBS inoculation and remained
      significantly increased at 30-36 h. We then examined the use of adjunctive
      therapy with antibody to TNF-alpha in animals with established GBS sepsis using
      polyclonal rabbit antirecombinant mouse TNF-alpha antiserum. Twelve hours after
      GBS inoculation, animals received a single dose of antibody to TNF-alpha or
      normal rabbit serum, and penicillin therapy (twice a day for 3 d) was begun.
      Animals receiving penicillin and antibody to TNF-alpha had a survival rate of 52%
      (13 of 25) versus 29% (7 of 24) for animals receiving penicillin and normal
      rabbit serum. Thus, the use of antibodies directed against TNF-alpha may have a
      role as adjunctive therapy of established GBS sepsis in the newborn infant.

PMID- 8559609
TI  - Extramedullary hematopoiesis and intratumoral production of cytokines in
      childhood hepatoblastoma.
AB  - Extramedullary hematopoiesis is a characteristic feature of hepatoblastoma (HB).
      We investigated 15 HB to characterize intratumoral hematopoietic foci and to find
      clues to the pathophysiology of their formation. By conventional histology and
      immunohistochemistry, we found erythroblasts in all and megakaryocytes in 10 of
      the HB, whereas granulocyte and monocyte precursor cells could not be identified
      in hematopoietic foci of any tumor. Only a minority of erythropoietic cells in
      these foci contained fetal Hb (HbF). We recently found that HB cells produce IL-1
      beta and thus stimulate stromal cells to secrete IL-6. We therefore searched for
      other hematopoietic cytokines in HB. Supernatants of primary HB cultures were
      subjected to ELISA, bioassayed, and immunoblotted. We detected erythropoietin
      (EPO) in 11 of 15, stem cell factor (SCF) in 7 of 11, granulocyte colony
      stimulating factor (G-CSF) in 4 of 15, granulocyte/macrophage colony-stimulating
      factor (GM-CSF) in 6 of 15, IL-3 in 1 of 12, leukemia inhibitory factor (LIF) in
      1 of 9, and macrophage colony-stimulating factor (M-CSF) in 1 of 8 conditioned
      media. With immunoenzymatic labeling we localized EPO and SCF to the cytoplasm of
      epithelial HB cells, whereas stromal cells and cells of immature fibrous tissue
      of mixed HB expressed SCF, G-CSF, GM-CSF, LIF, and M-CSF. EPO and SCF could also
      be detected in extracts of epithelial HB cells. We conclude that, in HB,
      erythropoiesis and megakaryopoiesis but not the granulocyte-macrophage lineage is
      induced by fetal and embryonal tumor cells in cooperation with stromal cells by
      locally secreted cytokines.

PMID- 8559610
TI  - Impaired D-myo-inositol 1,4,5-triphosphate generation from cord blood
      polymorphonuclear leukocytes.
AB  - D-myo-Inositol 1,4,5-triphosphate (IP3) is a key second messenger in many cells,
      including macrophages, T and B cells, and neutrophils, in which it regulates free
      intracellular calcium ion levels. In human polymorphonuclear leukocytes the rise
      of intracellular [Ca2+] is the signal that activates a number of functions such
      as adherence, aggregation, chemotaxis, and degranulation, which are typically
      depressed in newborn infants. IP3 generation can be stimulated by N-formyl
      methionyl-leucylphenylalanine (fMLP) tripeptide, which mimics the naturally
      occurring bacterial oligopeptides. In this study both neonatal and adult
      polymorphonuclear leukocytes were stimulated by fMLP (1 x 10(-6) M) and the
      levels of IP3 were assayed by a specific radiometric method. The time course of
      IP3 generation was studied for up to 60 s in a total of 10 samples. The response
      appeared reduced in cord blood samples. To confirm this observation, we extended
      our study to a larger number of samples, quantitating [IP3] at the time peak of
      10 s. As expected IP3 generation was significantly (F test, p < 0.0001, n = 39)
      lower in newborns than in adults (means +/- SD = 0.64 +/- 0.25; 1.26 +/- 0.36,
      ng/10(6) cells, respectively). Besides soluble stimulus, neutrophils were treated
      with a particulate stimulus, namely serum-treated zymosan, which is also able to
      stimulate IP3 synthesis from polymorphonuclear leukocytes. Serum-treated zymosan
      produced a prolonged elevation in the level of IP3, reaching a plateau within 120
      s in both cord blood and in control samples.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559611
TI  - Prognostic value of serum hyaluronic acid and type I and III procollagen
      propeptides in extrahepatic biliary atresia.
AB  - Although portoenterostomy has greatly improved the prognosis of extrahepatic
      biliary atresia (EHBA), 10-20% of patients still die before 5 y of age, and the
      only treatment option is liver transplantation (LT). To investigate whether these
      patients may be identified at an early stage, when the changes of successful LT
      are optimal, we have measured serum concentrations of hyaluronic acid (HA), the
      amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy
      terminal and amino-terminal propeptides of type I procollagen (PICP, PINP) in 24
      selected patients with EHBA, both before portoenterostomy and then every 6 mo
      until death (n = 10, age at death = 7-20 mo), LT (n = 6, age at LT = 1.1-4.8 y)
      or 5 y of age (n = 8). Raised serum HA above 200 micrograms/L before
      portoenterostomy identified those patients who would die or require LT in the
      first 5 y of life with a positive predictive value of 88%; after
      portoenterostomy, longitudinal changes in HA reflected clinical status in each
      patient. None of the other three markers was of prognostic value, and only PIIINP
      showed any relationship with clinical status, and then only up to 1.5 y.
      Interestingly, PINP (but not PICP) tended to be low in all patients before
      portoenterostomy and may reflect impaired bone collagen metabolism during early
      skeletal changes in EHBA. This study therefore suggests that measurement of serum
      HA may be a useful complementary test in EHBA, particularly in identifying, at an
      early stage, those patients who should be considered for LT.

PMID- 8559612
TI  - Ornithine decarboxylase and tyrosine kinase activity in juvenile polyps of
      childhood.
AB  - Juvenile polyps (JP) are the most common colonic tumor in children. Although
      considered benign, malignant transformation has been reported in JP. Ornithine
      decarboxylase (ODC) and tyrosine kinase (TyK) enzymes are markers for a rapid
      cell proliferation index. DNA aneuploidy score and p53 gene expression are late
      malignant changes seen in patients with colon cancer. In this study, we
      investigated ODC and TyK activities as well as DNA aneuploidy score and p53
      expression in juvenile polyps compared with the adjacent normal colonic mucosa.
      Results showed that ODC was significantly increased in JP compared with the
      adjacent normal colonic mucosa. TyK activity was increased in 3/5 polyps and
      decreased in 2/5 polyps compared with the mucosa. Mean TyK activity was higher in
      JP compared with normal mucosa but did not reach significance (707 and 632
      pmol/mg pmol, respectively). Moreover, changes in phosphorylization of TyK
      proteins was also observed in JP but not in normal mucosa. JP had a normal DNA
      aneuploidy score and showed no expression of p53 gene. We conclude that JP do not
      express p53 gene and aneuploidy but had higher activity of ODC and TyK enzymes,
      suggesting a higher stage of cell proliferation.

PMID- 8559613
TI  - Intravenous cysteamine therapy for nephropathic cystinosis.
AB  - A 4-y-old boy with nephropathic cystinosis and gastrointestinal dysmotility of
      unknown etiology was treated with i.v. cysteamine over a period of 10 mo. Thirty
      minutes after a dose of 10 mg/kg cysteamine free base, the leukocyte cystine
      value had fallen from 11.9 to 4.9 nmol of half-cystine/mg of protein. When
      cysteamine was given every 6 h, the leukocyte cystine concentration, measured 5-7
      h after a dose, decreased with increasing cysteamine doses up to 17 mg/kg; at
      this dose the cystine value was 1.1 nmol of half-cystine/mg of protein, or 9% of
      the untreated value. Oral administration of approximately 16 mg/kg per dose every
      6 h to this patient over the previous 3 y achieved similar leukocyte cystine
      depletion, to 1.2 nmol of half-cystine/mg of protein. The plasma cysteamine
      concentration 30 min after a dose of 10 mg/kg was 71 microM; 5-7 h after a dose
      of up to 20 mg/kg, the concentration was below 5 microM. Dimethylsulfide was
      elevated in the breath and urine of this boy after, but not before, the
      initiation of i.v. cysteamine therapy. Ten months after the start of therapy, the
      patient tolerated 250 mg (14 mg/kg) every 8 h. Adverse effects of this treatment
      included lethargy and increased nausea and vomiting when a schedule of therapy
      every 6 h was attempted. This investigation demonstrates that cysteamine given
      through a central venous catheter is effective in reducing leukocyte cystine
      levels.

PMID- 8559614
TI  - Intrauterine vitamin B2 uptake of preterm and full-term infants.
AB  - Intrauterine uptake of vitamin B2 in preterm and full-term infants was examined.
      Factors of influence on vitamin supply were considered. Forty-four women and
      their infants were included in the study. Fetal vitamin uptake was calculated as
      arteriovenous concentration gradient in cord plasma times umbilical plasma flow.
      Concentration of vitamin B2 (free riboflavin and flavocoenzymes) was determined
      by high performance liquid chromatography of placental tissue and blood plasma
      (maternal vein, umbilical artery, umbilical vein). Flavocoenzymes were analyzed
      as flavin mononucleotide after acid hydrolysis of flavin adenine dinucleotide.
      Umbilical plasma flow was measured using pulsed Doppler sonography. Both free
      riboflavin and flavocoenzymes were transferred from the maternal plasma to the
      umbilical vein, but only free riboflavin was accumulated (approximately 1:4 for
      preterm and full-term infants, respectively). Flavocoenzyme concentration was
      higher in the umbilical vein than in the umbilical artery (p < 0.05). This
      indicated a median uptake of flavocoenzymes of 1.5 nmol/min.kg in preterm infants
      and 0.4 nmol/min.kg in full-term infants (preterm versus full-term, p < 0.01).
      Fetal vitamin supply depended on umbilical plasma flow and on maternal vitamin
      status (the latter was shown only in full-term infants). No dependence on
      placental vitamin concentration was observed (p > 0.05). Concentration of free
      riboflavin was higher in umbilical artery than in umbilical vein (p < 0.05). This
      indicated a release of free riboflavin from fetal tissues independent of
      gestational age (0.4 nmol/min.kg, preterm; 0.2 nmol/min.kg, full-term; p > 0.05).

PMID- 8559615
TI  - Basal testosterone secretion and response to human luteinizing, follicle
      stimulating, and growth hormones in culture of cells isolated from testes of
      infants and children.
AB  - Little is known on the hormonal regulation of the early postnatal phase of Leydig
      cell activation in the human. Testosterone secretion by prepubertal testicular
      cells in culture was studied in two different age groups, 0-7-mo-old (group 1)
      and 16-36-mo-old (group 2) boys. A mixed cell preparation was isolated from
      testes collected at necropsy and maintained in culture for 6 d. Cells were
      cultured in serum-free medium in basal conditions and under the stimulation of
      human (h)LH, hFSH, or recombinant hGH, and the secretion of testosterone was
      determined on d 6 by RIA. In basal conditions, cells of group 1 secreted more
      testosterone (median 5.83 pmol/10(6) cells.d, n = 7) than cells of group 2
      (median 1.73, n = 5), p < 0.05, reflecting the steroidogenic potential of the
      testes in vivo. Under hLH stimulation, cells of group 1 responded by increasing
      testosterone secretion significantly. Surprisingly, hFSH stimulation elicited a
      similar response in cells of group 1. Because FSH receptors are presumably
      located in Sertoli cells, it is concluded that these cells secreted a paracrine
      factor that stimulated testosterone secretion by Leydig cells. On the other hand,
      recombinant hGH also stimulated the secretion of testosterone by cells of group
      1. Recombinant hGH could have interacted with either GH or prolactin receptors of
      testicular cells. Cells of group 2 did not respond to any stimulus. Because serum
      levels of LH, FSH, GH, and prolactin are higher during the first months of life
      than later in childhood, it is possible that the early postnatal activation of
      the testis is under multiple pituitary hormone influence.

PMID- 8559616
TI  - Diabetes in pregnancy: uterine blood flow and embryonic development in the rat.
AB  - The uterine blood flow to individual implantation sites was evaluated in early
      normal and diabetic rat pregnancy, and related to maternal metabolic state,
      length of gestation, and embryonic outcome. The aim was to search for a possible
      coupling between the flow rate and embryonic development. We studied pregnant
      rats of a malformation-prone Sprague-Dawley strain on gestational d 9, 10, 11,
      and 12, a time period which roughly corresponds to postconception wk 3-6 in human
      gestation. The blood flow in the uterus was estimated with the aid of a
      microsphere technique, and the embryos were evaluated with respect to morphology
      and uterine position. We found increased blood flow in the uterine and decidual
      tissue of the pregnant diabetic animals compared with normal pregnant rats on all
      days studied. The blood perfusion peaked on gestational d 10, both in normal and
      diabetic pregnancy. The implantations tended to be fewer, whereas the resorption
      and malformation rates were higher, in the left horn than in the right horn. The
      blood flow in the uterine and decidual tissues was increased in the left horn in
      diabetic d 10 tissue, as well as d 12 tissues, thereby suggesting that
      compromised embryonic development is associated with increased rather than
      decreased supply of nutrients to the implantation site. These findings are in
      concert with previous in vitro results suggesting that enhanced oxidative stress
      due to increased substrate availability is an important factor in diabetic
      teratogenesis.

PMID- 8559617
TI  - Longitudinal data on growth and final height in diabetic children.
AB  - The available data on growth in children with insulin-dependent diabetes mellitus
      are conflicting and are mainly derived from cross-sectional studies. In this
      longitudinal study, height, weight, skeletal age, and pubertal development were
      recorded until final height was attained in 46 children (22 girls and 24 boys)
      with onset of diabetes before the age of 10 y. At the onset of diabetes, height
      SD score (SDS) averaged 0.41 in girls and 0.56 in boys, which was normal when
      corrected for the secular trend. Prepubertal growth was unaffected in both sexes.
      Diabetic boys had a marked delay in onset of puberty (mean age at genitalia stage
      2: 13.7 y) but attained a normal final height (final height SDS: 0.48 +/- 0.89).
      In girls final height was slightly reduced (height SDS 0.27 +/- 0.97) due to a
      suboptimal pubertal growth spurt. Mean pubertal height gain in girls was 16.6 cm
      and mean age at breast stage 2 was 11.6 y. Diabetic girls also tended to become
      obese during puberty. Skeletal maturation was normal at all ages. These data
      suggest that conventional therapy does not guarantee optimal growth, especially
      in girls.

PMID- 8559618
TI  - The eight-year stability of problem behavior in an epidemiologic sample.
AB  - This study assessed the 8-y stability and change of parent-reported problem
      behaviors in 791 children from the general population assessed at 2-y intervals
      with the same standardized procedure, the child behavior checklist (CBCL).
      Problem behaviors were rather stable across even the relatively long time
      interval of 8 y. The 8-y stability coefficient for total problem score was 0.48,
      with somewhat higher stability for externalizing than internalizing problems.
      Despite stability, problem behaviors also changed considerably across time. These
      changes do not only reflect the increase in chronologic age. The present study
      showed that there are changes in children's problem levels that result from
      historical time influences. These secular trends seemed of even greater
      importance than aging effects, and reflect a slight increase of the norm of
      children's problem behaviors.

PMID- 8559619
TI  - Hepatitis C virus genotypes in serum and liver of children with chronic hepatitis
      C.
AB  - Hepatitis C virus (HCV) 1a, 1b, 2a, and 2b subtypes have been studied in 30 serum
      samples and in 20 paired liver biopsies from children with chronic hepatitis C.
      One serum sample was negative to the four HCV subtypes studied. HCV 1b was
      detected alone in 53.3% (16/30) of the serum samples; HCV 1a alone in 23.3%
      (7/30) and a mixed infection in 20% (6/30). In liver samples, HCV mixed infection
      was detected in a significantly higher proportion (50%: p < 0.05) than in serum,
      whereas HCV 1b was detected alone in 35% (7/20) and HCV 1a alone in the remaining
      15% (3/20) of liver samples. These results suggest that serum HCV genotyping may
      not reflect the viral population infecting the liver of a given patient.
      Additional studies should be performed concerning the pathobiology of hepatitis C
      virus with relation to the subtypes detected in liver.

PMID- 8559620
TI  - What to expect from medical treatment of otitis media.
AB  - 1. To state the expected rates of spontaneous improvement for untreated acute
      otitis media (AOM), recurrent AOM, and otitis media with effusion (OME). 2. To
      state the expected impact of antibiotic therapy on AOM, recurrent AOM, and OME in
      terms of the number of children needed to be treated to cure or prevent a single
      episode. 3. To explain why oral steroids are a promising, but unproven, treatment
      for OME. 4. To update and modify expectations for medical treatment of otitis
      media based on meta-analysis of randomized clinical trials.

PMID- 8559621
TI  - Varicella vaccine: its past, present and future.

PMID- 8559622
TI  - High prevalence of multidrug-resistant Streptococcus pneumoniae among children in
      a rural Kentucky community.
AB  - In 1992 drug-resistant Streptococcus pneumoniae was cultured with increasing
      frequency from aspirates of middle ear fluid from children with acute otitis
      media in a rural Kentucky community. To determine the prevalence of carriage of
      drug-resistant S. pneumoniae in the community, we obtained nasopharyngeal swabs
      from 158 (70%) of 227 children attending a child daycare center and from 82
      children attending the county health center. S. pneumoniae was isolated from 126
      children. Among 123 isolates tested 65 (53%) were penicillin-resistant, including
      41 (33%) strains that were highly resistant; 61 (50%) were multidrug-resistant.
      Serotypes 19F, 6B, 23F and 6A comprised 89% of the penicillin-resistant isolates.
      Detection of a variety of serotypes and drug resistance patterns among
      nasopharyngeal isolates of S. pneumoniae suggests that multidrug-resistant
      pneumococcal strains are endemic in this community. Surveillance for drug
      resistant pneumococci with the use of respiratory secretions obtained by
      nasopharyngeal swab may provide useful information on the prevalence of drug
      resistant strains causing invasive disease and otitis media. Such information
      could be used to guide empiric therapy of pneumococcal infections.

PMID- 8559623
TI  - Penicillin-resistant Streptococcus pneumoniae in acute otitis media: risk
      factors, susceptibility patterns and antimicrobial management.
AB  - From January, 1992, to January, 1994, penicillin-resistant (minimal inhibition
      concentration (MIC) > 0.06 microgram/ml) Streptococcus pneumoniae (PRSP) isolates
      accounted for 48 (17%) of 283 isolates from acute otitis media (AOM) or recurrent
      AOM in 246 ambulatory patients in rural Kentucky. By broth microdilution,
      relatively penicillin-resistant (MIC > 0.06 to 1.0 microgram/ml) and highly
      penicillin-resistant (MIC > or = 2.0 micrograms/ml) strains were detected in 25
      (16%) and 23 (15%), respectively, of 157 pneumococcal middle ear isolates. Using
      1994 National Committee for Clinical Laboratory Standards breakpoints for
      pneumococci (unavailable for oral cephalosporins except cefuroxime), highly PRSP
      strains were almost uniformly susceptible to clindamycin and vancomycin. In
      contrast highly PRSP strains were resistant to most oral antimicrobials
      customarily used for AOM with one-third of strains highly resistant (MIC > or =
      2.0 micrograms/ml) to ceftriaxone. Serotypes 6B, 19F and 23F accounted for 95% of
      highly PRSP strains and serotype 9V for 48% of relatively PRSP strains. By
      multivariate analysis, otitis-prone condition (P = 0.0008) and number of
      antibiotic courses before day of culture (P < 0.0001) were independently
      predictive of PRSP. Highly PRSP isolates were more commonly isolated from
      patients recently treated within 3 days (30%) vs. those who completed therapy
      more than 3 days earlier (2%) (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559624
TI  - Effect of antibiotic therapy on the outcome of outpatients with unsuspected
      bacteremia.
AB  - The records of 559 consecutive outpatient children with unsuspected bacteremia
      (467 Streptococcus pneumoniae) were reviewed. When compared with patients
      receiving oral or parenteral antibiotics, those patients who received no
      antibiotics at the initial visit were in follow-up: (1) less likely to be
      improved (32% vs. 86%, P < 0.01); (2) more likely to be febrile (75% vs. 28%, P <
      0.01); (3) more likely to be hospitalized (67% vs. 22%, P < 0.01); (4) more
      likely to have persistent bacteremia (28% vs. 3%, P < 0.01); and (5) more likely
      to have new focal infections (13% vs. 5%, P < 0.01). Compared with patients
      receiving parenteral antibiotics at the initial visit, patients receiving oral
      antibiotics were in follow-up: (1) less likely to be improved (81% vs. 89%, P <
      0.05); and (2) more likely to have persistent bacteremia (5% vs. 0%, P < 0.05).
      There was no statistical difference between patients receiving parenteral or oral
      therapy in the development of focal infections, although children with new focal
      infections receiving oral antibiotics more often had persistent or new positive
      cultures. No patients receiving parenteral antibiotics at the initial visit had
      positive blood or spinal fluid cultures at the follow-up visit. Analyses of the
      subgroups with (1) occult bacteremia with all organisms, (2) unsuspected
      bacteremia S. pneumoniae and (3) occult bacteremia with S. pneumoniae show
      results similar to those for the entire group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559625
TI  - Increased incidence and severity of Streptococcus pyogenes bacteremia in young
      children.
AB  - An increase in the incidence and severity of bacteremia caused by group A
      streptococci was noted in 1993 and 1994 in the Hadassah University Medical
      Center, Jerusalem. During the 6-year period 1987 to 1992, 12 children with group
      A streptococcal bacteremia were hospitalized, whereas in 1993 and 1994 there were
      17 patients, 5 of them with 1 each of the following severe clinical
      manifestations: meningitis and septic shock; streptococcal toxic shock syndrome;
      septic shock; pleural empyema; and fatal outcome. Our 29 patients with group A
      streptococcal bacteremia were younger than those reported in the literature: 10
      (35%) were < 3 months of age; 17 (59%) were < 1 year old. Most children were
      previously healthy and only 3 had an underlying immunodeficiency predisposing to
      infection (1 case each): leukemia; Di George syndrome; and congenital nephrotic
      syndrome. Two children were recovering from varicella. The skin was the most
      common site of primary infection (16 of 29). The average white blood cell (WBC)
      count was 18 150 cells/mm3 (range, 2200 to 34,200). The cases were not related
      epidemiologically and were caused by a variety of M-protein types. Polymerase
      chain reaction amplification of the genes encoding exotoxins A (speA) and C
      (speC) was done on 19 isolates and disclosed 2 strains positive for speA and 5
      positive for speC. One of the speA-positive isolates was from the single patient
      with toxic shock syndrome.

PMID- 8559626
TI  - Yersinia enterocolitica infection in children.
AB  - The clinical presentation, course and outcome of Yersinia enterocolitica
      infection was studied prospectively in 125 children. Enteric forms occurred in
      114 children (92 enteritis, 20 pseudoappendicitis, 2 chronic ileitis), of whom 17
      also had extramesenteric manifestations; 11 children had one or more
      extramesenteric forms without enteric disease. Enteritis occurred more frequently
      in young children whereas serious forms and extramesenteric forms were more
      common in children older than 6 years of age (P < 0.001). Arthritis was observed
      in 13 children and extensive lymphadenopathy in 11; 1 child had septicemia with
      pleurisy, 1 had vasculitis, 1 had cholecystitis and 4 had erythema nodosum.
      Diagnosis was established by positive culture in 100 (80%) children and by
      agglutinin test in 11 of 45 (24%), demonstration of circulating specific anti-IgA
      and anti-IgG to Yersinia outer membrane proteins in 47 of 48 (98%) and detection
      of antigen in biopsies in 28 of 33 (85%) children. The 2 latter methods were
      superior to the agglutinin test. Serotype O3 and O9 predominated. The frequency
      and seriousness of complications may justify the use of antibiotics for Yersinia
      enteritis in children 6 years of age or older.

PMID- 8559627
TI  - Neonatal Candida parapsilosis outbreak with a high case fatality rate.
AB  - A Candida parapsilosis outbreak of 58 cases in a neonatal intensive care unit
      lasted for 55 months. Patients infected by or colonized with C. parapsilosis were
      mainly very low birth weight infants (birth weight < 1500 g). Their mean birth
      weight was 817 g and their mean gestational age was 28 weeks. Statistical
      analysis including logistic regression confirmed that prematurity was the main
      risk factor. The analysis also suggested that C. parapsilosis infection (or
      colonization) was associated with a poor prognosis. In infants with gestational
      age < 29 weeks the risk for death in C. parapsilosis-infected patients was 16
      fold greater than in those with no C. parapsilosis infection. The case fatality
      rate of C. parapsilosis patients was higher than that of the controls (9 of 23
      vs. 1 of 40; P < 0.0001). The outbreak was most likely a result of cross
      infection because C. parapsilosis could be isolated only from the patients and
      from the hands of four nurses immediately after they had cared for a colonized
      patient. Cessation of the outbreak was temporally associated with long term
      parenteral fluconazole (6 mg/kg/day) prophylaxis.

PMID- 8559628
TI  - Cerebrospinal fluid shunt infections in children.
AB  - We reviewed cerebrospinal fluid (CSF) shunt infections treated in the Royal
      Children's Hospital, Melbourne from 1981 to 1991. Forty-one episodes of CSF shunt
      infection were found after 900 shunt operations, an infection rate of 4.5%.
      Clinical symptoms were nonspecific in 31.7% of episodes, and in 17.1% of episodes
      the initial CSF sample was normal on microscopy and biochemistry, although a
      pathogen was isolated on culture. Most episodes occurred within 4 months of the
      last operation on the shunt, the exception being infections caused by Haemophilus
      influenzae. Four patients died during treatment, but none could be attributed to
      infection alone. Treatment of suspected CSF shunt infection should not be
      withheld because of lack of firm clinical diagnosis or normal CSF microscopy, and
      episodes occurring more than 4 months after the last operation on the CSF shunt
      should receive antibiotic cover for H. influenzae.

PMID- 8559629
TI  - Echovirus type 9 epidemic in Kagoshima, southern Japan: seroepidemiology and
      clinical observation of aseptic meningitis.
AB  - An outbreak of aseptic meningitis caused by echovirus type 9 occurred between
      March and October, 1990, in Kagoshima, Southern Japan. Clinical manifestations
      and laboratory data of 259 children with aseptic meningitis who were admitted to
      the outpatient clinic of pediatrics in the Kagoshima City Hospital were analyzed
      (other diseases caused by echovirus type 9 were not investigated). The patients'
      age ranged from 1 month to 15 years and the highest incidence was in 4-year-old
      children. The male:female ratio was 1.3:1. Frequencies of headache (69%),
      vomiting (64%), neck stiffness (36%) and rash (195%) were lower than those in the
      previous reports in the United States or in the Europe. Pleocytosis in the
      cerebrospinal fluid increased with increasing age in the younger children. A
      predominance of neutrophils in cerebrospinal fluid lasted for 3 days or more
      after onset in 16% of the patients. Seroepidemiologic study suggested that the
      accumulation of susceptible children < 5 years of age had predisposed to the
      epidemic.

PMID- 8559630
TI  - Acellular pertussis vaccine as a booster dose for seventeen- to nineteen-month
      old children immunized with either whole cell or acellular pertussis vaccine at
      two, four and six months of age.
AB  - The safety and immunogenicity of two formulations of an acellular pertussis
      vaccine as a booster at 17 to 19 months of age were assessed in children
      immunized at 2, 4 and 6 months of age with acellular or whole cell pertussis
      vaccine. In Study I 86 children primed with a five-component acellular vaccine
      combined with diphtheria and tetanus toxoids or with a whole cell pertussis
      diphtheria-tetanus vaccine were boosted with the same vaccine. Local reactions
      (64% vs. 93%; relative risk, 0.7; 95% confidence interval, 0.5 to 0.9) and
      systemic reactions (68% vs. 97%; relative risk, 0.7; 95% confidence interval, 0.5
      to 0.9) were less common after the fourth dose of acellular vaccine than after
      the fourth dose of whole cell vaccine. In Study II 96 children primed with either
      an acellular or whole cell pertussis vaccine were boosted with an acellular
      vaccine. Local adverse reactions after booster immunization with acellular
      vaccine were more common in children primed with acellular vaccine than those
      primed with whole cell vaccine (68% vs. 33%; relative risk, 2.1; 95% confidence
      interval, 1.3 to 3.3). Antibody response to pertussis toxin, filamentous
      hemagglutinin and fimbriae were higher before and 1 month after the booster dose
      in children primed with the acellular vaccine. We conclude that the acellular
      pertussis vaccine is safe and immunogenic when used for the booster dose in
      children primed with either whole cell or acellular vaccine but is associated
      with local reactions.

PMID- 8559631
TI  - The antimeningococcal vaccine VAMENGOC B-C induced poor serum and salivary
      antibody response in young Brazilian children.
AB  - In 1989 about 2.3 million Brazilian children received the antimeningococcal
      vaccine VAMENGOC B-C (Havana, Cuba). We evaluated the serum and secretory immune
      response of vaccinated children by enzyme-linked immunosorbent assay with outer
      membrane complex antigens. Western blotting and bacterial adherence inhibition
      assays with human buccal epithelial cells were performed with some of the
      samples. Serum and salivary antibody concentrations to Neisseria meningitidis
      Group B of vaccinated children < 4 years old were not significantly higher than
      those of nonvaccinated children, as observed in convalescing patients used as
      positive controls. Older children (4 to 6 years old) presented a slight increase
      in antibody OD indexes. Sera and saliva from vaccinated children showed a weak
      reaction with meningococcal antigen by Western blotting and were unable to
      inhibit significantly the adherence of N. meningitidis B to buccal epithelial
      cells. These data suggest that this vaccine induced a poor serum and salivary
      antibody response in the population studied.

PMID- 8559632
TI  - Safety of imipenem in neonates.

PMID- 8559633
TI  - Bacteriology and beta-lactamase activity in ear aspirates of acute otitis media
      that failed amoxicillin therapy.

PMID- 8559634
TI  - Myelopathy as a presenting sign of acquired immunodeficiency syndrome.

PMID- 8559635
TI  - Severe varicella after low dose inhaled corticosteroids.

PMID- 8559636
TI  - Fatal air embolism as a complication of staphylococcal pneumonia with
      pneumatoceles.

PMID- 8559637
TI  - Acute acalculous cholecystitis associated with enteric fever in children.

PMID- 8559638
TI  - Bordetella holmesii sepsis in an asplenic adolescent.

PMID- 8559639
TI  - Burkholderia cepacia sepsis in neonates.

PMID- 8559640
TI  - Progressive vertebral blastomycosis mimicking tuberculosis.

PMID- 8559641
TI  - Congenital systemic candidiasis.

PMID- 8559642
TI  - A thirteen-year-old with a painful, swollen foot and eosinophilia.

PMID- 8559643
TI  - How long may perinatally acquired human immunodeficiency virus infection last
      asymptomatically?

PMID- 8559644
TI  - Cat-scratch disease: single or multiple causative microorganisms?

PMID- 8559645
TI  - Monitoring trends in acute rheumatic fever in the United States.

PMID- 8559646
TI  - Cord blood may be inappropriate for sensitive assays.

PMID- 8559647
TI  - 18th European Conference on Visual Perception. Tubingen, Germany, 21-25 August
      1995. Abstracts.

PMID- 8559648
TI  - 1st Congress of the Federation of European Physiological Societies. Maastricht,
      The Netherlands, 9-12 September 1995. Abstracts.

PMID- 8559649
TI  - RBP-J kappa repression activity is mediated by a co-repressor and antagonized by
      the Epstein-Barr virus transcription factor EBNA2.
AB  - The Epstein-Barr virus (EBV) protein EBNA2 is a transcriptional activator that
      can be targeted to its DNA responsive elements by direct interaction with the
      cellular protein RBP-J kappa. RBP-J kappa is a ubiquitous factor, highly
      conserved between man, mouse and Drosophila, whose function in mammalian cells is
      largely unknown. Here we provide evidence that RBP-J kappa is a transcriptional
      repressor and, more importantly, that RBP-J kappa repression is mediated by a co
      repressor. The function of the co-repressor could be counterbalanced by making a
      fusion protein (RBP-VP16) between RBP-J kappa and the VP16 activation domain.
      This RBP-VP16-mediated activation could be strongly increased by an EBNA2 protein
      deprived of its activation domain, but not by an EBNA2 protein incapable of
      making physical contact with RBP-J kappa. Our results suggest that EBNA2
      activates transcription by both interfering with the function of a co-repressor
      recruited by RBP-J kappa and providing an activation domain.

PMID- 8559650
TI  - Characterization of hybridization between synthetic oligodeoxynucleotides and RNA
      in living cells.
AB  - Cells internalized synthetic oligonucleotides (oligos) in culture. The
      hybridization of these molecules to target RNA in the living cell was
      subsequently detected and characterized after fixation of the cells, with or
      without previous detergent extraction. Hybridized oligo was distinguished from
      free oligo in the cell using an in situ reverse transcription technique. This
      assay exploited the ability of the hybridized oligo to prime synthesis of a
      specific cDNA strand; unhybridized oligo present in the cell could not act as a
      primer for reverse transcription. Phosphorothioate and fluorochrome-labeled
      phosphodiester oligo dT were found to enter cells rapidly and hybridize to poly
      (A) RNA within 30 min. Hybrids containing phosphorothioate oligo dT were
      detectable in cells after up to 4 h of efflux time. Phosphodiester bonded oligo
      dT containing covalently-linked fluorochromes appeared more stable in the cell
      than unmodified phosphodiester oligo dT; hybrids containing these oligos could be
      detected in cells as long as 18h after efflux began. The in situ transcription
      assay was also sensitive enough to detect hybridization of anti-actin oligos to
      actin mRNA in the cell. It is probable, therefore, that this assay can be used to
      help assess the efficacy of antisense oligos by their hybridization to a target
      mRNA in cells or tissues; hybridized oligos are more likely to induce a specific
      antisense effect. Additionally, this assay will help to identify probes that
      would be useful as stable hybridization tags to follow RNA movement in living
      cells.

PMID- 8559651
TI  - Efficient hammerhead ribozyme-mediated cleavage of the structured hepatitis B
      virus encapsidation signal in vitro and in cell extracts, but not in intact
      cells.
AB  - Hepatitis B virus (HBV), the causative agent of B-type hepatitis in man, is a
      small enveloped DNA virus that replicates through reverse transcription of an RNA
      intermediate, the terminally redundant RNA pregenome. An essential highly
      conserved cis-element present twice on this RNA is the encapsidation signal
      epsilon, a stem-loop structure that is critical for pregenome packaging and
      reverse transcription. Epsilon is hence an attractive target for antiviral
      therapy. Its structure, however, is a potential obstacle to antivirals whose
      action depends on hybridization, e.g. ribozymes. Here we demonstrate effective in
      vitro cleavage inside epsilon by hammerhead ribozymes containing flanking
      sequences complementary to an adjacent less structured region. Upon co
      transfection with a HBV expression construct corresponding ribozymes embedded in
      a U6 snRNA context led to a significant, though modest, reduction in the steady
      state level of HBV pregenomes. Inactive ribozyme mutants revealed that antisense
      effects contributed substantially to this reduction, however, efficient epsilon
      cleavage by the intracellularly expressed ribozymes was observed in Mg(2+)
      supplemented cell lysates. Artificial HBV pregenomes carrying the ribozymes in
      cis and model RNAs lacking all HBV sequences except epsilon exhibited essentially
      the same behaviour. Hence, neither the absence of co-localization of ribozyme and
      target nor a viral component, but rather a cellular factor(s), is responsible for
      the strikingly different ribozyme activities inside cells and in cellular
      extracts.

PMID- 8559652
TI  - Identification of a 67 kDa protein that binds specifically to the pre-rRNA
      primary processing site in a higher plant.
AB  - In radish pre-rRNA primary processing cleavage occurs at a UUUUCGCGC element
      (motif P) mapped in the 5'-external transcribed spacer (Delcasso-Tremousaygue et
      al., 1988). Significantly, motif P is part of a cluster of homologous elements
      including three UUUUCCGG elements (motifs A123) and a single UUUUGCCCC element
      (motif B). Here we used the EMSA to identify in radish extracts an RNA-binding
      activity, NF C, that specifically interacts with the pre-rRNA A123BP sequence.
      Using different RNA probes and competitors we show that NF C recognises a 38 base
      RNA sequence including the 3'-end of motif A3 and motifs B and P. NF C binds to
      poly U, but not to poly A, poly C or poly G. Therefore we used poly (U) Sepharose
      chromatography as a final step to obtain pure NF C fractions. These, analysed by
      SDS-PAGE, revealed two major polypeptides of 67 and 60 kDa. According to UV cross
      linking analysis the 67 kDa polypeptide corresponds to NF C activity, while the
      60 kDa species is a proteolysed form of this protein. We also showed that NF C is
      enriched in nuclear extracts. Based on its stringent RNA substrate specificity
      and its nuclear localisation we propose that NF C is involved in pre-rRNA primary
      processing in plants.

PMID- 8559653
TI  - Preference of the recombination sites involved in the formation of
      extrachromosomal copies of the human alphoid Sau3A repeat family.
AB  - The human alphoid Sau3A repetitive family DNA is one of the DNA species that are
      actively amplified to form extrachromosomal circular DNA in several cell lines.
      The circularization takes place between two of the five approximately 170 bp
      subunits with an average of 73.1% homology as well as between identical subunits.
      To investigate the nature of the recombination reaction, we cloned and analyzed
      the subunits containing recombination junctions. Analysis of a total of 68
      junctions revealed that recombination had occurred preferentially at four
      positions 10-25 (A), 40-50 (B), 85-90 (C) and 135-160 (D) in the 170bp subunit
      structure. Two regions (B and C) were overlapped with the regions with higher
      homology between subunits, while other two regions (A and D) cannot be explained
      solely by the regional homology between the subunits. These regions were located
      at both junctions of the nucleosomal and the linker region, and overlapped with
      the binding motifs for alpha protein and CENP-B. Approximately 90% of the
      recombination occurred between the subunits located next but one (+/- 2 shift),
      although the frequency of recombination between the adjoining subunits (+/- 1
      shift) was approximately 10%.

PMID- 8559654
TI  - Transcription factors interacting with herpes simplex virus alpha gene promoters
      in sensory neurons.
AB  - Interference with VP16-mediated activation of herpes virus immediate-early (or
      alpha) genes is thought to be the major cause of establishing viral latency in
      sensory neurons. This could be brought about by lack of a key activating
      transcription factor(s) or active repression. In this study we find that sensory
      neurons express all important components for VP16-mediated alpha gene induction,
      such as the POU transcription factor Oct-1, host cell factor (HCF) and GABP
      alpha/beta. However, Oct-1 and GABP alpha/beta are only present at low levels and
      the VP16-induced complex (VIC) appears different. We do not find protein
      expression of the transcription factor Oct-2, implicated by others as an alpha
      gene repressor. The POU factor N-Oct3 (Brn 2 or POU3F2) is also present in
      sensory neurons and binds viral TAATGARAT motifs with higher affinity than Oct-1,
      indicating that it may be a candidate repressor for competitive binding to
      TAATGARAT motifs. When transfected into HeLa cells, where Oct-1 and GABP
      alpha/beta are highly abundant, N-Oct3 represses model promoters with
      multimerized TAATGARAT motifs, but fails to repress complete alpha gene
      promoters. Taken together our findings suggest that modulation of alpha gene
      promoters could contribute to viral latency when low concentrations of the
      activating transcription factors Oct-1 and GABP alpha/beta prevail. Our data,
      however, refute the notion that competing Oct factors are able to block alpha
      gene transcription to achieve viral latency.

PMID- 8559655
TI  - Identification of the fifth subunit of Saccharomyces cerevisiae replication
      factor C.
AB  - Yeast replication factor C (RF-C) is a multipolypeptide complex required for
      chromosomal DNA replication. Previously this complex was known to consist of at
      least four subunits. We here report the identification of a fifth RF-C subunit
      from Saccharomyces cerevisiae, encoded by the RFC5 (YBR0810) gene. This subunit
      exhibits highest homology to the 38 kDa subunit (38%) of human RF-C (activator
      1). Like the other four RFC genes, the RFC5 gene is essential for yeast
      viability, indicating an essential function for each subunit. RFC5 mRNA is
      expressed at steady-state levels throughout the mitotic cell cycle. Upon
      overexpression in Escherichia coli Rfc5p has an apparent molecular mass of 41
      kDa. Overproduction of RF-C activity in yeast is dependent on overexpression of
      the RFC5 gene together with overexpression of the RFC1-4 genes, indicating that
      the RFC5 gene product forms an integral subunit of this replication factor.

PMID- 8559656
TI  - A new DNA sequence assembly program.
AB  - We describe the Genome Assembly Program (GAP), a new program for DNA sequence
      assembly. The program is suitable for large and small projects, a variety of
      strategies and can handle data from a range of sequencing instruments. It retains
      the useful components of our previous work, but includes many novel ideas and
      methods. Many of these methods have been made possible by the program's
      completely new, and highly interactive, graphical user interface. The program
      provides many visual clues to the current state of a sequencing project and
      allows users to interact in intuitive and graphical ways with their data. The
      program has tools to display and manipulate the various types of data that help
      to solve and check difficult assemblies, particularly those in repetitive
      genomes. We have introduced the following new displays: the Contig Selector, the
      Contig Comparator, the Template Display, the Restriction Enzyme Map and the Stop
      Codon Map. We have also made it possible to have any number of Contig Editors and
      Contig Joining Editors running simultaneously even on the same contig. The
      program also includes a new 'Directed Assembly' algorithm and routines for
      automatically detecting unfinished segments of sequence, to which it suggests
      experimental solutions.

PMID- 8559657
TI  - Stereodifferentiation--the effect of P chirality of oligo(nucleoside
      phosphorothioates) on the activity of bacterial RNase H.
AB  - P stereoregular phosphorothioate analogs of pentadecamer 5'-d(AGATGTTTGAGCTCT)-3'
      were synthesized by the oxathiaphospholane method. Their diastereomeric purity
      was assigned by means of enzymatic degradation with nuclease P1 and,
      independently, with snake venom phosphodiesterase. DNA-RNA hybrids formed by
      phosphorothioate oligonucleotides (PS-oligos) with the corresponding
      complementary pentadecaribonucleotide were treated with bacterial RNase H. The
      DNA-RNA complex containing the PS-oligo of [all-RP] configuration was found to be
      more susceptible to RNase H-dependent degradation of the pentadecaribonucleotide
      compared with hybrids containing either the [all-SP] counterpart or the so called
      'random mixture of diastereomers' of the pentadeca(nucleoside phosphorothioate).
      This stereodependence of RNase H action was also observed for a
      polyribonucleotide (475 nt) hybridized with these phosphorothioate
      oligonucleotides. The results of melting studies of PS-oligo-RNA hybrids allowed
      a rationalization of the observed stereodifferentiation in terms of the higher
      stability of heterodimers formed between oligoribonucleotides and [all-RP]
      oligo(nucleoside phosphorothioates), compared with the less stable heterodimers
      formed with [all-SP]-oligo(nucleoside phosphorothioates) or the random mixture of
      diastereomers.

PMID- 8559658
TI  - RNA:DNA complex formation upon transcription of immunoglobulin switch regions:
      implications for the mechanism and regulation of class switch recombination.
AB  - Central the regulation and mechanism of class switch recombination is the
      understanding of the relationship between transcription and DNA recombination. We
      demonstrated previously, using mini-chromosome substrates, that physiologically
      oriented transcription is required for recombination to occur between switch
      regions. In this report, we demonstrate the formation of an RNA:DNA complex under
      in vitro transcription conditions for these same and other switch DNA fragments.
      We find that cell-free transcription of repetitive murine switch regions (Smu, S
      gamma 2b and S gamma 3) leads to altered DNA mobility on agarose gels. These
      altered mobilities are resistant to RNase A but sensitive to RNase H.
      Transcription in the presence of labeled ribonucleotides demonstrates the stable
      physical association of the RNA with the DNA. Importantly, complex formation only
      occurs upon transcription in the physiologic orientation. Reaban and Griffin
      [1990 Nature, 348, 342-344] found an RNA:DNA hybrid structure that was limited to
      an atypical 143 nucleotide purine region within a 2.3 kb S alpha segment. Here we
      demonstrate RNA:DNA hybrid formation in more typical switch sequences (lacking
      the atypical 143 nucleotide purine tract) from a variety of switch regions that
      are only 60-70% purine on the non-template strand. These results suggest a
      general model involving an RNA:DNA complex as an intermediate during class switch
      recombination.

PMID- 8559659
TI  - Double-strand breaks at the target locus stimulate gene targeting in embryonic
      stem cells.
AB  - Double-strand breaks (DSBs) are recombinogenic lesions in chromosomal DNA in
      yeast, Drosophila and Caenorhabditis elegans. Recent studies in mammalian cells
      utilizing the I-Scel endonuclease have demonstrated that in some immortalized
      cell lines DSBs in chromosomal DNA are also recombinogenic. We have now tested
      embryonic stem (ES) cells, a non-transformed mouse cell line frequently used in
      gene targeting studies. We find that a DSB introduced by I-Scel stimulates gene
      targeting at a selectable neo locus at least 50-fold. The enhanced level of
      targeting is achieved by transient expression of the I-Scel endonuclease. In 97%
      of targeted clones a single base pair polymorphism in the transfected homologous
      fragment was incorporated into the target locus. Analysis of the targeted locus
      demonstrated that most of the homologous recombination events were 'two-sided',
      in contrast to previous studies in 3T3 cells in which 'one-sided' homologous
      events predominated. Thus ES cells may be more faithful in incorporating
      homologous fragments into their genome than other cells in culture.

PMID- 8559660
TI  - Stabilization of RNA stacking by pseudouridine.
AB  - The effect of the modified nucleoside pseudouridine (psi) on RNA structure was
      compared with uridine. The extent of base stacking in model RNA oligonucleotides
      was measured by 1H NMR, UV, and CD spectroscopy. The UV and CD results indicate
      that the model single-stranded oligoribonucleotides AAUA and AA psi A form
      stacked structures in solution and the CD results for AA psi A are consistent
      with a general A-form helical conformation. The AA psi A oligomer exhibits a
      greater degree of UV hypochromicity over the temperature range 5-55 degrees C,
      consistent with a better stacked, more A-form structure compared with AAUA. The
      extent of stacking for each nucleotide residue was inferred from the percent 3'
      endo sugar conformation as indicated by the H1'-H2' NMR scalar coupling. This
      indirect indication of stacking was confirmed by sequential NOE experiments. NMR
      measurements as a function of temperature indicate that pseudouridine forms a
      more stable base stacking arrangement than uridine, an effect that is propagated
      throughout the helix to stabilize stacking of neighboring purine nucleosides. The
      N1-H imino proton in AA psi A exchanges slowly with solvent, suggesting a role
      for the extra imino proton in stabilizing the conformation of pseudouridine.
      These results show that the conformational stabilization is an intrinsic property
      of pseudouridine occurring at the nucleotide level. The characteristics of
      pseudouridine in these models are consistent with earlier studies on intact rRNA,
      indicating that pseudouridine probably performs the same stabilizing function in
      most structural contexts.

PMID- 8559661
TI  - Trans-complementation by human apurinic endonuclease (Ape) of hypersensitivity to
      DNA damage and spontaneous mutator phenotype in apn1-yeast.
AB  - Abasic (AP) sites in DNA are potentially lethal and mutagenic. 'Class II' AP
      endonucleases initiate the repair of these and other DNA lesions. In yeast, the
      predominant enzyme of this type is Apn1, and its elimination sensitizes the cells
      to killing by simple alkylating agents or oxidants, and raises the rate of
      spontaneous mutation. We investigated the ability of the major human class II AP
      endonuclease, Ape, which is structurally unrelated to Apn1, to replace the yeast
      enzyme in vivo. Confocal immunomicroscopy studies indicate that approximately 25%
      of the Ape expressed in yeast is present in the nucleus. High-level Ape
      expression corresponding to approximately 7000 molecules per nucleus, equal to
      the normal Apn1 copy number, restored resistance to methyl methanesulfonate to
      near wild-type levels in Apn1-deficient (apn1-) yeast. Ape expression in apn1-
      yeast provided little protection against H2O2 challenges, consistent with the
      weak 3'-repair diesterase activity of the human enzyme. Ape expression at
      approximately 2000 molecules per nucleus reduced the spontaneous mutation rate of
      apn1- yeast to that seen for wild-type cells. Because Ape has a powerful AP
      endonuclease but weak 3'-diesterase activity, these findings indicate that
      endogenously generated AP sites can drive spontaneous mutagenesis.

PMID- 8559662
TI  - Thyroid hormone receptors bind to the promoter of the mouse histone H10 gene and
      modulate its transcription.
AB  - It has been shown that the mouse histone H10 promoter contains a DNA element,
      composed of a direct repeat of the sequence GGTGACC separated by 7 nt, which is
      able to bind retinoic acid receptors and to modulate transcription of reporter
      genes following treatment with retinoic acid. We have now investigated whether
      this DNA motif is also responsive to thyroid hormone. We co-transfected CV-1
      monkey kidney cells with chloramphenicol acetyltransferase (CAT) expression
      plasmids containing either 740 bp of the H10 wild-type promoter or five copies of
      the repeat element cloned in front of the thymidine kinase promoter and
      expression vectors for human thyroid hormone receptors (TRs) alpha or beta and
      retinoid X receptor alpha (RXR alpha). Treatment of transfected cells with
      triiodothyronine led to a dose-dependent increase in CAT activity. Transfection
      experiments with increasing amounts of expression vectors for either TR alpha or
      RXR alpha resulted in up to 6-fold enhancement of CAT transcription. Furthermore,
      point mutations within the half-sites of the response element of the H10
      promoter, as well as deletions within the interspace region, lowered CAT activity
      to 60-80% of that of the wild-type control. Electrophoretic mobility shift assays
      showed that the repeat element was able to form retarded complexes with TR alpha
      homodimers, as well as with TR alpha-RXR alpha heterodimers. Our results suggest
      that thyroid hormone receptors are involved in the regulation of mouse histone
      H10 expression.

PMID- 8559663
TI  - Identification of the interleukin-6/oncostatin M response element in the rat
      tissue inhibitor of metalloproteinases-1 (TIMP-1) promoter.
AB  - The rat tissue inhibitor of metalloproteinase 1 (TIMP-1) gene is expressed in rat
      hepatocytes, and this expression is up-regulated by interleukin 6 (IL-6). We
      report here the cloning of the 5' flanking region of the rat TIMP-1 gene and
      identification of an IL-6/oncostatin M (OSM) response element at -64 to -36 which
      functions in hepatic cells. Within this element we have identified two functional
      binding sites for transcription factors AP-1 (activatory protein-1) and STAT
      (signal transducer and activator of transcription). IL-6/OSM stimulation induces
      binding of a protein, identified as STAT3, to the IL-6/OSM response element,
      while binding of the AP-1 protein was constitutive. Binding sites for both AP-1
      and STAT3 are necessary for full responsiveness of the TIMP-1 promoter to IL
      6/OSM, as shown by deletion and mutation analysis. Furthermore, the entire IL
      6/OSM response element conferred responsiveness onto a heterologous promoter,
      whereas this has not been observed when AP-1 and STAT elements were separately
      tested.

PMID- 8559664
TI  - Specific binding of the replication protein of plasmid pPS10 to direct and
      inverted repeats is mediated by an HTH motif.
AB  - The initiator protein of the plasmid pPS10, RepA, has a putative helix-turn-helix
      (HTH) motif at its C-terminal end. RepA dimers bind to an inverted repeat at the
      repA promoter (repAP) to autoregulate RepA synthesis. [D. Garcia de Viedma, et
      al. (1996) EMBO J. in press]. RepA monomers bind to four direct repeats at the
      origin of replication (oriV) to initiate pPS10 replication This report shows that
      randomly generated mutations in RepA, associated with defficiencies in
      autoregulation, map either at the putative HTH motif or in its vicinity. These
      mutant proteins do not promote pPS10 replication and are severely affected in
      binding to both the repAP and oriV regions in vitro. Revertants of a mutant that
      map in the vicinity of the HTH motif have been obtained and correspond to a
      second amino acid substitution far upstream of the motif. However, reversion of
      mutants that map in the helices of the motif occurs less frequently, at least by
      an order of magnitude. All these data indicate that the helices of the HTH motif
      play an essential role in specific RepA-DNA interactions, although additional
      regions also seem to be involved in DNA binding activity. Some mutations have
      slightly different effects in replication and autoregulation, suggesting that the
      role of the HTH motif in the interaction of RepA dimers or monomers with their
      respective DNA targets (IR or DR) is not the same.

PMID- 8559665
TI  - A novel PRD I and TG binding activity involved in virus-induced transcription of
      IFN-A genes.
AB  - Comparative analysis of the inducible elements of the mouse interferon A4 and A11
      gene promoters (IE-A4 and IE-A11) by transient transfection experiments, DNase 1
      footprinting and electrophoretic mobility shift assays resulted in identification
      of a virus-induced binding activity suggested to be involved in NDV-induced
      activation of transcription of these genes. The virus-induced factor, termed VIF,
      is activated early by contact of virions with cells. It specifically recognizes
      the PRD I-like domain shared by both inducible elements, as well as the TG-like
      domain of IE-A4. This factor, distinct from the IRF-1, IRF-2 and the alpha F1
      binding proteins and presenting a different affinity pattern from that of the TG
      protein, is proposed as a candidate for IFN-type I gene regulation.

PMID- 8559666
TI  - Characterization of a silencer element in the first exon of the human osteocalcin
      gene.
AB  - Osteocalcin, the major non-collagenous protein in bone, is transcribed in
      osteoblasts at the onset of extracellular matrix mineralization. In this study it
      was demonstrated that sequences located in the first exon of the human
      osteocalcin gene possess a differentiation-related osteocalcin silencer element
      (OSE). Osteocalcin was rendered transcribable in UMR-106 cells and proliferating
      normal osteoblasts after deletion of the -3 to +51 region. Site-specific
      mutagenesis of this region revealed that a 7 bp sequence (TGGCCCT) (+29 to +35)
      is critical for silencing function. Mobility shift assays demonstrated that a
      nuclear factor bound to the OSE. The OSE binding protein was present in
      proliferating normal pre-osteoblasts and in UMR-106 and ROS 17/2.8 osteosarcoma
      cells, but was absent from post-proliferative normal osteoblasts. The binding
      protein was inhibited by fragments containing the +29/+35 sequence, but not by
      other promoter fragments or by the consensus oligomers of unrelated nuclear
      factors AP-1 and Sp1. DNase 1 footprinting demonstrated that the OSE binding
      protein protected the +17 to +36 portion of the first exon, consistent with the
      results of mapping studies and competitive mobility shift assays. It is
      hypothesized that this silencer is activated by complexing of the OSE binding
      protein to the OSE during the osteoblast proliferation stage and that the OSE
      binding protein is down-regulated at the onset of extracellular matrix
      mineralization.

PMID- 8559667
TI  - Characterization and cloning of p11, a transrepressor of Drosophila melanogaster
      retrotransposon 1731.
AB  - The NssBF element has been characterized as a 26 nt sequence in the long terminal
      repeat of Drosophila melanogaster retrotransposon 1731. This sequence has been
      shown to be implicated in transcriptional repression of the 1731 promoter. We
      here report the cloning of a cDNA encoding a nuclear DNA binding protein named
      p11 that binds specifically to the NssBF element. P11 is a 98 amino acid
      polypeptide. It exhibits similarities with the mouse p9 single-stranded DNA
      binding protein, raising the possibility of a very general family of protein
      factors. Co-transfection experiments in human U937 cells showed repression of the
      1731 promoter by overexpression of p11.

PMID- 8559668
TI  - A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene
      segments including deletion in germ cells.

PMID- 8559669
TI  - Improved strategy for mutation detection--a modification to the enzyme mismatch
      cleavage method.

PMID- 8559670
TI  - A new horizon for pBR322: in vivo insertion of plasmid fragments into wide host
      range shuttle vectors.

PMID- 8559672
TI  - Professional development. Digestive tract cancers: the role of the nurse
      (continuing education credit).

PMID- 8559671
TI  - A simple, rapid method for isolation of high quality genomic DNA from animal
      tissues.

PMID- 8559673
TI  - Maddening inaction.

PMID- 8559674
TI  - Laboured relations. Interview by Daloni Carlisle.

PMID- 8559675
TI  - New year, new editor. Interview by Tricia Reid.

PMID- 8559676
TI  - Intensive questions.

PMID- 8559677
TI  - How Swedish nurses are tackling nurse prescribing.
AB  - The prescription of a limited range of products by nurses in the UK is now into
      its second year of evaluation. This paper describes a visit made to study nurse
      prescribing in Sweden. The Swedish scheme is analysed and compared with the
      system being developed in the UK. One scheme involves prescribing with a
      protocol, while the other involves diagnosis and treatment.

PMID- 8559678
TI  - Nurse prescribing. The case for prescribing the pill.
AB  - As the law stands, nurses cannot prescribe the oral contraceptive pill. However,
      it is an open secret that many technical contraventions of the law occur. The
      nurses at the Margaret Pyke Centre have carried out a pilot study for the re
      issuing of oral contraceptives by designated nurses. The aim is to regularise
      practice within the existing law and to help nurses acquire the authority to
      prescribe in future. This paper presents the interim findings of the study which
      suggest that clinical nurse specialists and experienced family planning nurses
      should prescribe the oral contraceptive pill to healthy women.

PMID- 8559679
TI  - Nasopharyngeal suction study reveals knowledge deficit.
AB  - Nasopharyngeal suction is carried out frequently in paediatric practice. A
      questionnaire survey was distributed to nurses and physiotherapists at The Royal
      Hospital for Sick Children in Edinburgh to ascertain the extent of their
      knowledge in the theory and practice of suctioning. Results revealed several
      problem areas in use of nasopharyngeal suction at this hospital. There was
      significant disagreement over appropriate catheter size, suction pressure and
      method of suction as well as use of pre-oxygenation and knowledge of adverse
      effects. The results indicate that further theoretical and practical education is
      needed in the use of nasopharyngeal suction and that a standard method should be
      implemented throughout the hospital.

PMID- 8559680
TI  - Systems of life. The adrenal gland 2.

PMID- 8559681
TI  - Christmas: Leavesden revisited.

PMID- 8559682
TI  - Christmas: 20th century foxed.

PMID- 8559683
TI  - Christmas. Pagan party.

PMID- 8559684
TI  - Mothers' help.

PMID- 8559685
TI  - A war of starvation.

PMID- 8559686
TI  - Clinch the ideal.

PMID- 8559687
TI  - Continence. Toilets out of order.

PMID- 8559688
TI  - Continence. Easing the social stress.

PMID- 8559689
TI  - The importance of outcome studies.

PMID- 8559690
TI  - The impact of managed care on musculoskeletal physical treatment.

PMID- 8559691
TI  - The effectiveness of cut-proof glove liners: cut and puncture resistance,
      dexterity, and sensibility.
AB  - Five types of commercial glove liners (within double latex gloves) were compared
      to single and double latex gloves for cut and puncture resistance and for
      relative manual dexterity and degree of sensibility. An apparatus was constructed
      to test glove-pseudofinger constructs in either a cutting or puncture mode.
      Cutting forces, cutting speed, and type of blade (serrated or scalpel blade) were
      varied and the time to cut-through measured by an electrical conductivity
      circuit. Penetration forces were similarly determined with a scalpel blade and a
      suture needle using a spring scale loading apparatus. Dexterity was measured with
      an object placement task among a group of orthopedic surgeons. Sensibility was
      assessed with Semmes-Weinstein monofilaments, two-point discrimination, and
      vibrametry using standard techniques and rating scales. A subjective evaluation
      was performed at the end of testing. Time to cut-through for the liners ranged
      from 2 to 30 seconds for a rapid oscillating scalpel and 4 to 40 seconds for a
      rapid oscillating serrated knife under minimal loads. When a 1 kg load was added,
      times to cut-through ranged from 0.4 to 1.0 second. In most cases, the liners
      were superior to double latex. On average, 100% more force was required to
      penetrate the liners with a scalpel and 50% more force was required to penetrate
      the liners with a suture needle compared to double latex. Object placement task
      times were not significantly liners compared to double latex gloves. Semmes
      Weinstein monofilaments, two-point discrimination, and vibrametry showed no
      difference in sensibility among the various liners and double latex gloves.
      Subjects felt that the liners were minimally to moderately impairing. An
      acclimation period may be required for their effective use.

PMID- 8559692
TI  - Assessment of patellar height after autogenous patellar tendon anterior cruciate
      ligament reconstruction.
AB  - In this study, we sought to determine if a significant change in patellar height
      occurs after autogenous patellar tendon anterior cruciate ligament (ACL)
      reconstruction at our clinic. In a series of 71 patients (52 males and 18
      females; average age: 22 years; range: 12 to 41) randomly selected, all had
      undergone an identical autogenous patellar tendon ACL reconstruction, by the same
      surgeon, and followed the same postoperative accelerated rehabilitation program.
      All patients had standardized preoperative and postoperative lateral knee
      radiographs. The patellar tendon length as well as the patellar height and ratio
      of Blackburne and Peel were measured by the same person for all subjects. The
      length of the patellar tendon shortened by an average of 0.4 mm (range: 6%
      lengthening to 12% shortening) which is less than 1% and not statistically
      significant (P = .068). The Blackburne and Peel ratio for patellar height
      decreased by 1%, which was also not statistically significant (P = .060). The
      evidence obtained from this study indicated no significant change in patellar
      height after autogenous patellar tendon ACL reconstruction combined with
      postoperative accelerated rehabilitation and no correlations with postoperative
      complications, secondary surgeries, timing of surgery, age, or anterior knee
      symptoms.

PMID- 8559693
TI  - Free vascularized temporal parietal flap in hand surgery.
AB  - Free vascularized temporo-parietal fascia (TPF) flap is a flap of thin, pliable
      and vascularized tissue which can cover an area measuring up to 12 cm x 14 cm.
      The flap is harvested based on temporal vessels, which provide a smooth, gliding
      surface for tendon function and eliminates the need for secondary procedures
      usually required by the pedicled or bulky free vascularized myocutaneous flaps.
      The donor pedicle is long and consistent with an average diameter of 3 mm in
      adults. This flap is versatile. In 12 resurfacings for traumatic wounds of hand
      and wrist, no flaps were lost. Donor site morbidity, except for a transient
      sideburn hair loss in one case, was not encountered. We recommend this flap as a
      viable one-stage procedure for coverage of complex hand wounds.

PMID- 8559694
TI  - Intraoperative complications during total hip arthroplasty.
AB  - Total hip replacement is one of the most common adult reconstructive procedures
      performed today. Even though training in total hip replacement has become fairly
      common in many orthopedic residency programs, complications can still occur
      during surgery. Preoperative planning and close attention to detail may prevent
      intraoperative problems. Awareness of the potential downfalls allows the surgeon
      to properly prepare for surgery, avoid intraoperative complications, and manage
      unavoidable problems when they do arise.

PMID- 8559695
TI  - Electromyography and biomechanics of a dynamic knee brace for anterior cruciate
      ligament deficiency.
AB  - Twelve anterior cruciate ligament (ACL)-deficient subjects performed concentric
      isokinetic knee extensions at maximum effort both with and without the Bledsoe
      Pro Shifter knee brace. Electromyogram signals from the quadriceps, hamstrings,
      knee angle, and the extension force were recorded and evaluated to determine the
      effects of such dynamic bracing on muscle activity and joint stability. High
      activity, or asymptomatic, subjects (n = 5) experienced no change in muscle
      activity, but displayed a decrease in extension force throughout the active range
      of the brace. Low activity, or symptomatic, subjects (n = 7) exhibited increased
      quadriceps activity and decreased hamstrings activity, and displayed a minor
      increase in force in the mid-range (80 degrees to 40 degrees flexion). These
      results indicate that dynamic bracing prevents quadriceps inhibition in
      symptomatic subjects by exerting a posteriorly directed force to the superior
      tibia; thus, the brace compensates externally for the absence of the ACL.

PMID- 8559697
TI  - Nonunion of an olecranon epiphyseal plate stress fracture in an adolescent.

PMID- 8559696
TI  - Patella tendon rupture: a late complication of a tibial nail.

PMID- 8559698
TI  - Compartment syndrome in the leg requiring fasciotomy after bicillin injection in
      the thigh.

PMID- 8559699
TI  - Disseminated intravascular coagulopathy (DIC) complicating intramedullary
      fixation of impending femur fracture from metastatic prostate cancer.

PMID- 8559700
TI  - The shelf sign indicating instability in minimally displaced extraarticular
      distal radial fractures.

PMID- 8559701
TI  - What's new in cardiology!

PMID- 8559702
TI  - Family-focused behavioral pediatrics: clinical techniques for primary care.
AB  - Whenever a behavioral or psychosocial problem presents in a child, all members of
      the family are affected. Conversely, when the problem lies within the family, the
      child is affected and often presents as the symptomatic patient. The goals of
      family-focused pediatrics are to: 1) determine the need for a family
      intervention; 2) conduct a family interview-assessment; 3) clarify the issues; 4)
      teach healthy communication skills and interactions; and 5) facilitate generation
      of family goals and solutions. Family-focused strategies provide an effective,
      brief, and timely approach that can aid the pediatrician in helping children and
      their families function in more healthy and satisfying ways.

PMID- 8559703
TI  - Hodgkin disease.

PMID- 8559704
TI  - The child who has a limp.

PMID- 8559705
TI  - Preparing for pediatric emergencies.

PMID- 8559706
TI  - Corrosive ingestions.

PMID- 8559707
TI  - Erythema infectiosum (fifth disease).

PMID- 8559708
TI  - Choanal atresia.

PMID- 8559709
TI  - Uveitis.

PMID- 8559710
TI  - Cold, cough, and allergy medications: uses and abuses.

PMID- 8559711
TI  - Staphylococcal scalded skin syndrome.

PMID- 8559712
TI  - Leukocyte disorders: quantitative and qualitative disorders of the neutrophil,
      Part 1.

PMID- 8559713
TI  - Blunt trauma to the abdomen.

PMID- 8559714
TI  - Index of suspicion. Case 1. Typhoid fever.

PMID- 8559715
TI  - Index of suspicion. Case 2. Myasthenia gravis.

PMID- 8559716
TI  - Index of suspicion. Case 3. Hypertensive encephalopathy.

PMID- 8559717
TI  - Hypnosis: teaching children self-regulation.

PMID- 8559718
TI  - Two-way selection for threshold body weight at first egg in broiler strain
      females. 5. Replication of results in a two-generation selection experiment.
AB  - Selection for high and low threshold weight for onset of lay (ThrWtLay), carried
      out in a broiler line over six generations, was previously found to increase
      reproductive performance in the low line (LL). Because of the potential
      importance of this effect, a two-generation replication of the original
      experiment was carried out using a modern broiler line. Selection was on the
      basis of ThrWtLay, measured as body weight at first egg, following gradual
      release from feed restriction. The total response to selection over two
      generations was 382 g, giving a realized heritability of .42. The difference in 6
      wk body weight of the two lines was +19 g in favor (P > .05) of the high line
      (HL). Reproductive performance was measured in the S2 generation and in the first
      (R1) generation of relaxed selection. On the average, age at first egg of LL was
      17.6 d earlier, and prepeak, postpeak, and total egg production of LL to a fixed
      age was 9.9, 1.1, and 11.1 eggs greater, respectively, than that of HL. The
      differences in age at first egg, prepeak, and total egg production were
      significant; those in postpeak production were not. There was a difference of 1.1
      g in favor (P > .05) of HL for egg weight. Thus, the results of this short-term
      selection experiment are broadly consistent with those of the original, long-term
      selection. Namely, ThrWtLay responded strongly to selection, with a powerful
      accompanied response in age at onset of lay and in prepeak egg production, and
      only a small effect on 6-wk body weight. However, in contrast to the results
      obtained previously, LL in the present experiment showed only a small increase (P
      > .05) in postpeak production relative to HL. Nevertheless, although an effect on
      postpeak production was not obtained in the present experiment, the results do
      provide general support for the previously expressed view that selection for
      early onset of lay, on release from feed restriction, may provide a means of
      increasing photoperiodic drive and consequent reproductive performance of broiler
      breeders.

PMID- 8559719
TI  - Comparison of index selection and best linear unbiased prediction for simulated
      layer poultry data.
AB  - The advantage of using best linear unbiased prediction (BLUP) of breeding value
      over different selection indexes was examined for a sex-limited trait in a
      simulated layer poultry population. The base breeding population consisted of 30
      males and 300 females that were unrelated to each other. Heritability for
      different analyses was assumed to be either .1, .2, or .5. Each generation was
      reproduced from two hatches each year, with a hatch variance of 3.165% of the
      phenotypic variance, except for one simulation, in which it was assumed to be 40%
      to test the effect of a large fixed effect. Parents were selected on 1) BLUP of
      breeding value, 2) optimum selection index (individual, full-, and half-sibs), 3)
      classical selection index (as for optimum, but index weight constant across
      generations), 4) reduced selection index (individual and full-sibs only), or 5)
      combination of classical and BLUP. The relative selection response with the
      selection indices compared to the BLUP estimates (except for the reduced
      selection index) were from 94.5 to 99.4% of BLUP. Inbreeding was higher in the
      BLUP selected populations, which could offset any advantage of BLUP if the
      populations were structured so that inbreeding could rise too rapidly.

PMID- 8559720
TI  - Nutritional homeostatic capacity of a three-breed cross in poultry and associated
      effects of genotypes at the pea comb and endogenous viral element 1 loci.
AB  - The effect of varying combinations of dietary CP, at 16, 18, and 20%, with ME, at
      2,900 and 3,100 kcal ME/kg, on BW and feed conversion (FC) at 2 to 6 wk of age
      for a three-breed cross was evaluated. Additionally, effect of genotypes at the
      pea comb (P) and endogenous viral element 1 (ev1) loci on dietary treatments were
      evaluated. Average weekly feed intake per bird varied from 25.6 to 32.6 g for
      birds on 16% CP, 3,100 kcal ME/kg and 20% CP, 2,900 kcal ME/kg diets,
      respectively. Weekly BW and FC were highest for birds on a combination of 20% CP
      and 3,100 kcal ME/kg diet. On 18% CP and 3,100 kcal/ME diet, males with pea comb
      had significantly higher BW than those with a single comb. At the ev1 locus,
      differences among genotypes were significant only for BW of females on a diet
      consisting of 20% CP and 2,900 kcal ME/kg. Pooled data from the dietary
      treatments revealed that males with pea comb had significantly higher BW than
      males with single comb at 3 to 6 wk of age. Birds heterozygous at the ev1 locus
      had higher BW than those homozygous at this locus. Results of the current studies
      provide information necessary to develop the optimal protein and energy
      combination for BW and FC for a three-breed cross involving Araucona, White
      Leghorn, and Rhode Island Red. These studies also provide additional evidence of
      the possible effects of the P locus and a gene linked to it, ev1, on production
      traits in chickens.

PMID- 8559721
TI  - Bronchodilator, oxygen level, and temperature effects on ascites incidence in
      broiler chickens.
AB  - Oxygen level, ambient temperature, and bronchodilator (metaproterenol) effects on
      performance, ascites incidence, and hematology were investigated using commercial
      broilers. In Experiment 1, two atmospheric oxygen concentrations (17.6, 20.6%)
      and two ambient temperatures (26.7, 32.2 C) were examined in a factorial
      arrangement. The low-oxygen (17.6%), ambient temperature combination (26.7 C)
      reduced (P < .01) weight gain whereas the high-oxygen ambient temperature
      combination enhanced (P < .05) such performance. Ascites incidence for chicks
      housed at 32.2 C was higher (P < .01) for birds maintained at 17.6% oxygen but
      oxygen concentration did not impact ascites incidence at 26.7 C. White blood cell
      counts were elevated in the low-oxygen (17.6%) group at both 26.7 and 32.2 C, and
      hematocrit was positively (R = .84; P < .05) correlated with ascites incidence.
      In Experiment 2, two oxygen levels (17.6, 20.6%) at constant 26.7 C were examined
      with and without metaproterenol, a bronchodilator. Metaproterenol reduced (P <
      .01) ascites incidence at 17.6% oxygen and completely prevented ascites at 20.6%
      oxygen. The data suggest that therapeutic development may be enhanced by using
      hematocrit as an indices of ascites and further that studies directed at
      bronchodilation have potential to alleviate ascites.

PMID- 8559722
TI  - Does pulmonary hypertension syndrome (ascites) occur more frequently in broilers
      medicated with monensin?
AB  - The performance of broilers reared in floor pens and given monensin in the feed
      at 121 ppm was compared with that of birds given no drug. Feed intake and BW gain
      of medicated birds was significantly lower than that of unmedicated birds from 0
      to 22 d of age. Feed intake and feed conversion of medicated birds was
      significantly reduced, compared with unmedicated birds, from 22 to 53 and 0 to 60
      d of age. Total mortality, and mortality due to leg abnormalities from 22 to 53
      and 0 to 60 d, was significantly lower in birds given monensin. There was no
      difference in the incidence of tibial dyschondroplasia (TD) by 60 d. No
      differences in mortality due to pulmonary hypertension syndrome (PHS) were
      observed for any age period. Birds removed from pens at 28 d that had received
      monensin had lower hematocrit and percentage saturation of hemoglobin with oxygen
      in the blood than unmedicated birds. No differences in these variables were found
      at 54 d. There were no differences in the right ventricle weight: total
      ventricular weight ratios or electrocardiogram lead II values at 28 or 54 d. The
      results indicate that PHS does not occur more frequently in broilers medicated
      with monensin.

PMID- 8559723
TI  - The effect of in ovo oocyst or sporocyst inoculation on response to subsequent
      coccidial challenge.
AB  - A trial was conducted to investigate the effects of in ovo Eimeria maxima
      inoculation on response to subsequent posthatch challenge with E. maxima. The in
      ovo treatments were arranged in a 4 x 2 factorial with four in ovo inoculation
      sites (air cell, amnion, yolk sac, and allantois) and two parasite forms (oocyst
      and sporocyst). Four control treatments included an uninoculated (naive)
      unchallenged group, a naive challenged group, and two posthatch inoculated
      challenged groups. Chicks were challenged by crop intubation with 50,000
      sporulated E. maxima oocysts 10 d posthatch. On Day 8 postchallenge, feed intake
      was determined and birds were weighed and lesions scored. During the brooding
      period, oocysts were isolated from the fecal material of chicks receiving in ovo
      administration of sporocysts in the amnion and sporocysts or oocysts in the yolk
      sac. Posthatch inoculated chicks had gain and feed:gain ratios similar to those
      of naive unchallenged chicks. Gain, feed:gain ratio, lesion scores, and oocyst
      shedding of chicks inoculated in ovo were similar to those of naive, challenged
      chicks. Although there was some indication that parasites introduced in ovo may
      complete their life-cycle within the developing chick, this experiment provided
      no evidence that in ovo administration of either E. maxima oocysts or sporocysts
      will protect birds from subsequent coccidial challenge. Contrarily, inoculating
      chicks on day of hatch with a single oral dose of E. maxima oocysts provided
      significant protection against subsequent coccidial challenge.

PMID- 8559724
TI  - Sheep red blood cell and Brucella abortus antibody responses in chickens selected
      for multitrait immunocompetence.
AB  - Chickens from replicated lines divergently selected for multitrait
      immunocompetence were tested for their antibody responses to sheep red blood
      cells and Brucella abortus antigen. All birds were injected with sheep red blood
      cells and B. abortus antigens at 4 and 9 wk of age, and blood samples were taken
      6, 8, and 10 d postimmunization. Antibody titers were determined by using
      agglutination assays. For sheep red blood cell responses, the most marked
      difference was between the high and low lines postsecondary immunization. The
      high line titer was still rising at 10 d, whereas the low line had reached its
      peak at 8 d and was decreasing. This may be a result of the selection process in
      which the high line is selected for a high, persistent response to two T cell
      dependent antigens at 3 wk postimmunization. For B. abortus responses, the only
      differences were between high and low lines postsecondary immunization. The high
      lines were always higher than the low lines, with differences getting smaller as
      time postimmunization increased. In summary, selection for multitrait
      immunocompetence resulted in changes in antibody response to unrelated antigens.

PMID- 8559725
TI  - Mitigating the effects of halofuginone on skin strength by feeding L-proline to
      broiler chickens.
AB  - Two experiments were conducted to determine whether supplemental levels of L
      proline in the diets of broiler chickens would mitigate the skin weakening effect
      caused by continuous feeding of the anticoccidial halofuginone. In Experiment 1,
      tensile strength and collagen levels in thigh apteria skin were determined at 21
      and 42 d of age in male broilers fed 0, .5, and 1% L-proline with either
      halofuginone (3 mg/kg) or salinomycin (61 mg/kg). In Experiment 2, the same
      measurements were made on female broilers receiving diets containing halofuginone
      and supplemented with 0, .5, or 1% L-proline, 1% L-proline through 21 d of age,
      or 1% L-glutamic acid through 21 d of age, or a diet containing high L-proline
      feedstuffs (corn gluten meal and ring dried blood meal). In Experiment 1, dermis
      thickness of thigh apteria was measured in the males at Day 21. Skin strength was
      increased in male and female broilers fed halofuginone with addition of .5 and 1%
      L-proline, respectively, at 21 and 42 d of age. Continuous incorporation of
      synthetic L-proline into diets was shown to improve skin strength in females,
      whereas diets formulated to contain high levels of L-proline from feedstuffs, 21
      d feeding of L-proline, or L-glutamic acid did not increase skin strength.

PMID- 8559726
TI  - Posthatch changes in morphology and function of the small intestines in heavy-
      and light-strain chicks.
AB  - The morphology of the small intestines of heavy (Arbor Acres) and light (Lohman)
      chicks was determined posthatch in parallel with digestion, enzyme secretion, and
      passage time. Villus height and volume increased from 4 to 10 d, particularly in
      the jejunum and ileum. The number of enterocytes per villus increased with age,
      but enterocyte density was greater in jejunum than ileum. Villus volume and
      enterocyte density was greater in Arbor Acres than Lohman chicks from hatching
      and the rate of change with age was similar in both strains. Enzyme secretion to
      the duodenum was higher per gram of feed intake in heavy-strain birds on Day 4
      after hatching but thereafter no differences were apparent. Passage time was 50%
      shorter in light-strain chicks on Day 4 but the difference between the strains
      was not significant from Day 10. No differences in fatty acid digestion were
      observed with age or between strains. Nitrogen digestion increased in both
      strains from approximately 70% on Day 4 to close to 90% on Day 14. Starch
      digestion was 90 to 95% from 4 to 14 d in Arbor Acres birds, but increased from
      approximately 80% on Day 4 in Lohman chicks to 93% on Day 14. Feed intake may
      determine the amount of uptake in posthatch chicks.

PMID- 8559727
TI  - Effect of feeding raw and treated common vetch seed (Vicia sativa) on the
      performance and egg quality parameters of laying hens.
AB  - Two experiments were conducted to study the effect of feeding raw or treated
      common vetch seeds (V) on BW, feed intake (FI), egg production (EP), feed
      conversion (FC), egg weight (EW), shell thickness (ST), yolk color score (YC),
      and Haugh unit score (HU) of Single Comb White Leghorn hens for 56 d. In
      Experiment 1, diets contained 0, 7.5, 15, and 22.5% raw V. Compared with the
      control, the 22.5% V diet decreased (P < .05) BW, FI, and EP. In Experiment 2,
      intact or ground (G) V were either soaked (S) in water (1:5) for 24 h or
      autoclaved (A) at 103.5 x 10(3) Pa for 8 h, and then dried (D) at 55 C for 24 h.
      Eight diets were used, a corn soybean (control) and seven others, each containing
      25% V, previously subjected to the forementioned treatments as follows: untreated
      V (UV), SDV, GSDV, ADV, GADV, SADV, and GSADV. Compared with the control, the UV
      diet decreased (P < .05) FI (75 vs 98 g) and EP (47.3 vs 88.7%), increased FC
      (1.99 vs 1.4 kg feed per dozen eggs), and induced BW loss (-63 vs 49 g). Soaking
      intact V improved (P < .05) FI (85 g) and EP (69%). Remaining treatments resulted
      in further improvement. Hens fed all V diets produced eggs with HU score 13
      points better than that of the control (P < .05). In both experiments, EW, YC,
      and ST were not different among treatments. Results indicated that autoclaved V
      at 25% level was not detrimental to layers' performance.

PMID- 8559728
TI  - Effect of full feed and early feed restriction on broiler performance, abdominal
      fat level, cellularity, and fat metabolism in broiler chickens.
AB  - Three hundred sixty Peterson x Arbor Acres chicks were fed two feed regimens to
      compare their effects on adipose cellularity, adipocyte lipolysis, hepatic
      glucose oxidation, adipocyte lipogenesis, bird performance, and abdominal fat
      level. Broilers in the first regimen had ad libitum access to feed throughout the
      7-wk experiment, whereas broilers in the second regimen consumed feed at will
      throughout the experiment except that they were subjected to feed restriction
      (1.49 kcal/g BW2/3 daily) from 7 to 12 d of age (DOA). No differences in mean
      body weights were observed between the full-fed and restricted males and combined
      sex broilers at 49 DOA. Feed conversion and abdominal fat levels of female and
      combined sex were lower (P < .05) for the restricted than full-fed broilers. No
      differences in adipocyte numbers based either on whole abdominal fat pads at 28
      and 42 DOA or per gram fat at 42 DOA were observed between broilers fed the two
      feed regimens. However, the adipocyte numbers per gram fat at 28 DOA were greater
      (P < .05) for the restricted broiler than for the broilers that ate freely.
      Lipolysis based per million adipocytes was not different between the treatments
      at 28 and 42 DOA; however, lipolysis based on per gram adipose tissue was
      increased (P < .05) with the addition of isoproterenol and theophylline for the
      restricted broilers compared to the full-fed broilers at 28 DOA. No difference
      was observed between the feed regimens at 42 DOA with hormone addition.
      Lipogenesis of the restricted broilers was lower (P < .05) than that of the full
      fed broilers at 14 and 56 DOA. No difference in glucose oxidation was found
      between chickens fed the two regimens. Reduced abdominal fat in the restricted
      broilers is attributed to the reduction of adipocyte volume, which may be due to
      decreased lipogenesis.

PMID- 8559729
TI  - A method to determine and factors that influence in vivo solubilization of
      phosphates in commercial Leghorn hens.
AB  - Experiments 1 and 2 were conducted to establish a technique for the recovery of
      dietary phosphates from commercial layer manure. Solutions of ethanol, 60%
      ethanol:40% water (vol/vol), 50% ethanol:50% water, 40% ethanol:60% water, and
      100% water were tested to determine the efficacy of dicalcium phosphate recovery.
      Solutions containing 50% or greater ethanol were found to be most effective.
      Experiments 3 and 4 were conducted to determine factors that influence in vivo
      phosphate solubilization in commercial Leghorn hens. In Experiment 3, mono
      dicalcium phosphate (Biofos), di-monocalcium phosphate (Dynafos), and tricalcium
      phosphate (Multifos) were fed to layers at 1.67 and 3.3 g hen/d levels. In vivo
      phosphate solubilization was higher (P < or = .05) for Biofos and Dynafos than
      for Multifos. Dietary phosphate level did not consistently influence in vivo
      phosphate solubilization in hens. In Experiment 4, a 3 x 2 x 2 factorial
      arrangement consisting of three types of phosphates (Biofos, Dynafos, and
      Multifos), two dietary levels of added P (.3 and .6%), and two levels of dietary
      Ca (.88 and 3.75%) were used. In vivo phosphate solubilization decreased as Ca
      level was increased. In vivo solubilization of Multifos was lower than Biofos or
      Dynafos at both dietary Ca levels tested. These results indicate that phosphate
      source and calcium level, but not phosphorus level, consistently influence in
      vivo solubilization of phosphates.

PMID- 8559730
TI  - Characterization of carcass development from 14 to 145 days of age in turkey hens
      from two strains.
AB  - Body weight and carcass components were measured from 14 to 145 d in Nicholas
      (NIC) and Hybrid (HYB) strain turkey hens. At most ages, BW of HYB hens was
      greater than that of NIC and there were small but significant differences in the
      weight of the Pectoralis minor (PMIN). The relative weight of the PMIN increased
      in HYB hens from 98 to 145 d. No strain differences in either the absolute or
      relative weights of the Pectoralis major (PMAJ) were observed. The absolute and
      relative weights of the tibia plus associated muscles (DRUM) and femur plus
      associated muscles (THIGH) were significantly heavier in HYB hens. The same was
      true for the Gastrocnemius muscle (GASTROC). The relative weight of the abdominal
      fat pad (ABFAT) was significantly increased in NIC hens compared with HYB hens
      from 70 to 145 d. There was a linear relationship between the relative weight of
      the PMAJ and BW in hens from both strains (NIC, r2 = .69; HYB, r2 = .51). The
      relationship between the relative weight of the PMIN and BW was best described
      with a quadratic model but the r2 in both strains was considerably lower than
      that for the PMAJ (NIC, r2 = .26; HYB, r2 = .36). The linear relationship between
      BW and the relative weights of the THIGH and DRUM was negative and positive for
      ABFAT.

PMID- 8559731
TI  - Chemical and physical evaluations of commercial dicalcium phosphates as sources
      of phosphorus in animal nutrition.
AB  - Seven samples of commercial dicalcium phosphate, expected to contain variable
      amounts of monocalcium phosphate, from five established producers in Brazil and
      two in the United States, were evaluated and compared with a purified grade
      calcium phosphate dibasic dihydrate used as a reference standard. All samples
      were submitted to a wide range of tests at seven laboratories. Each determination
      was performed at least at two different laboratories, except for moisture,
      insoluble residue, loss on ignition, and x-ray diffraction assays, obtained from
      one single laboratory. All phosphate samples studied were in compliance with the
      manufacturer's levels of guarantee, except for three samples that were slightly
      out of specification (Ca, P, and F). Particle size patterns were variable,
      allowing for a classification of two products as "coarse", three as "fine", and
      three as "irregular". Phosphorus solubility in 2% citric acid ranged from 85.9 to
      97.6%, pH from 3.2 to 6.1, and apparent density from 572 to 967 g/L. Atomic
      absorption or plasma emission spectrometry concentrations (average parts per
      million) for Al (3,200), As (10), B (14), Ba (165), Bi (< .1), Cd (6), Cr (57),
      Co (11), Cu (28), Fe (7,515), Hg (< .2), Mg (11,300), Mn (367), Mo (6), Ni (25),
      Pb (17), Se (< .5), Sb (1.3), Th (19), U (51), V (134), W (< 5), and Zn (152)
      were safe for all phosphates as compared to NRC standards. X-ray diffraction
      detected CaCO3 and impurities for all commercial samples, dolomite for three
      phosphates. Monocalcium phosphate was found in four samples. Aluminum salts
      present were identified as the low solubility, low toxicity silicates, and
      phosphates.

PMID- 8559732
TI  - Morphologic characteristics of oviducts from hens producing eggs of different
      Haugh units caused by genetics and by feeding vanadium as determined with
      computer software-integrated digitizing technology.
AB  - Magnum and isthmus morphologic characteristics (surface epithelium height, fold
      height and diameter, and periodic acid-Schiff-positive area and surface
      epithelium cells) of stained 6-micron tissue sections were measured by light
      microscopy, with data acquisition using a digitizing tablet interfaced to a
      microscope and to a personal computer with morphometric-dimensional software.
      Tissues were obtained from Leghorn layers in two separate experiments in which
      production of eggs with low and high Haugh unit (HU) values was induced by either
      genetic selection or by feeding V. Eggs produced by these hens had HU differences
      between the high and low groups of 11 to 14 units (both experiments, P = .0001)
      and had a greater volume of thick albumen fraction in high-HU groups (both
      experiments, P = .0001). The computer software-integrated digitizing system
      enabled rapid measurements of multiple characteristics. In the genetic lines,
      higher magnum fold height and magnum and isthmus surface epithelium height were
      detected at moderate significance (all at P < .05) in the tissues of the layers
      producing high-HU eggs than in tissues from the low-HU line. Other morphologic
      variables were not different between genetic lines. In response to feeding V,
      none of the morphological characteristics were affected, although magnum fold
      height approached difference at P < .07. Based on the observations in these two
      experiments, magnum fold height may be a further important factor related to egg
      albumen condition, in addition to surface epithelium height. It appears, however,
      that layers producing eggs of considerably different HU values, due in these
      experiments to genetics or V feeding, can have magnum or isthmus morphological
      characteristics that are indistinguishable, or only moderately different, as
      detected by integrated digitizing technology.

PMID- 8559733
TI  - Pulmonary arteriole hypertrophy in broilers with pulmonary hypertension syndrome
      (ascites).
AB  - Two experiments were conducted to determine the effect of low ventilation or cool
      temperature environments on pulmonary arteriole hypertrophy. Male broilers were
      maintained under control or low ventilation conditions in Experiment 1, whereas
      male broiler breeder by-product chicks were exposed to cool temperature
      conditions in Experiment 2. Birds were randomly selected for histological
      evaluation of lung tissue in both experiments. In Experiment 1, birds that had
      pulmonary hypertension syndrome (PHS+) exhibited a greater degree of inflammation
      of lung tissue at 5 and 7 wk of age than controls or birds that did not have PHS
      (PHS-). These PHS+ birds also had higher numbers of cartilaginous osseous nodules
      at 3 and 7 wk of age than controls. Morphometric analyses revealed that PHS+
      birds in Experiment 1 had a thicker medial layer associated with 100 to 200
      microns diameter pulmonary arterioles at 7 wk of age, and 50 to 100 microns
      arterioles at 3 and 7 wk of age than PHS- or control birds. In Experiment 2, PHS+
      birds exhibited a thicker medial layer in pulmonary arterioles at 7 wk of age
      than did PHS- birds, but there were no differences in medial layer thickness at 5
      wk of age nor were there differences in the degree of inflammation or amount of
      osseous nodule formation between PHS+ and PHS- birds at 5 and 7 wk of age. Thus,
      pulmonary arteriole hypertrophy was observed in birds having PHS in response to
      both low ventilation and cool temperature environments and this hypertrophy
      occurred with or without a coincident inflammatory response in lung tissue.

PMID- 8559734
TI  - Ostrich slaughter and fabrication: 1. Slaughter yields of carcasses and effects
      of electrical stimulation on post-mortem pH.
AB  - A commercial ostrich slaughter protocol was developed. Ostriches (n = 7 males and
      n = 7 females) averaged 95.54 kg live weight and yielded 55.91-kg carcasses. By
      product yields were measured. The most significant by-products by weight were
      full viscera (8.29 kg), hide (6.71 kg), full gizzard and crop (5.80 kg), and
      abdominal fat (4.11 kg). Sex had no effect on slaughter yields. Post-mortem
      temperature declines were measured on five separate muscles and showed that
      chilling for 24 h was sufficient to adequately chill the deep muscle temperature
      to under 4 C. The effect of electrical stimulation on post-mortem pH decline also
      was investigated and had no effect.

PMID- 8559735
TI  - Nutritional value for growing turkeys of corn of light test weight.
AB  - An experiment was conducted to determine the relationship between test weight of
      corn and growth, efficiency of feed utilization, nutrient retention, and carcass
      composition of young turkeys. The MEn values of corn were also measured. Two
      samples of corn differing substantially in test weight were fed to male turkey
      poults (Nicholas Large White) from 1 to 20 d of age. The test weights of the
      light-weight corn and the normal-weight corn were 55 kg/hL (43 lb/bu) and 70
      kg/hL (54 lb/bu), respectively. The light-weight corn was lower in crude protein
      concentration (6.63%) than the normal-weight corn (8.53%). The determined MEn of
      the corn samples did not differ (3.22 vs 3.25 kcal/g). The light-weight corn diet
      had modest adverse effects on growth and feed efficiency of poults during the 1
      to 7 d after hatching. Poult carcass composition and retention of nitrogen and
      energy were not affected by the test weight of corn.

PMID- 8559736
TI  - Correlation of plasma calcium with experimentally elevated cholesterol and
      triglycerides in laying hens.
AB  - An experiment was conducted to determine the relationship between plasma Ca,
      cholesterol, and triglycerides in commercial laying hens. A 2 x 2 factorial
      arrangement of treatments was used with two levels of dietary iodine (0 and 5,000
      ppm) from KI and two levels of beta-estradiol (0 and 12 mg in a single
      subcutaneous injection), in a corn oil carrier. Feeding iodine or injecting beta
      estradiol resulted in increased plasma Ca, cholesterol and triglycerides. The
      increases were additive for the two treatments. Plasma Ca and cholesterol was
      significantly correlated. Plasma Ca was negatively correlated with triglycerides
      when the hens were injected with beta-estradiol. Cholesterol and triglycerides
      were correlated when hens were injected with beta-estradiol. However, feeding KI
      decreased the correlation between Ca and triglycerides, and cholesterol and
      triglycerides.

PMID- 8559737
TI  - Atherosclerosis in Japanese Quail males selected for high or low plasma
      cholesterol.
AB  - Three lines of Japanese quail males, unselected controls (CL), high response
      (HL), and low response (LL) lines, selected for plasma total cholesterol for 18
      generations, were fed all-plant source, nonatherogenic diets to which 0 or .5%
      cholesterol were added from 6 to 18 wk of age. Atherosclerotic scores (AS) of
      aorta of HL birds fed cholesterol were significantly higher than those of LL
      birds fed cholesterol. Scores of LL fed cholesterol were not higher than LL not
      fed cholesterol. Fatty infiltration of muscularis and foam cell disruption of
      elastic fibers were observed in HL males fed cholesterol. In a second experiment,
      males of the three lines were fed from 6 to 14 wk of age four plant source diets
      to which were added: 1) 10% glucose monohydrate (cerelose); 2) 10% cerelose + .1%
      cholesterol; 3) 4% corn oil; or 4) 4% coconut oil. All diets were calculated to
      be isocaloric and isonitrogenous. Overall, AS of HL and CL males were
      significantly higher than LL males, but there were no effects of diet for the 56
      d feeding period.

PMID- 8559738
TI  - 10th American Association of Pharmaceutical Scientists (AAPS) annual meeting.
      Miami Beach, Florida, November 5-9, 1995. Abstracts.

PMID- 8559739
TI  - [Intelligence and language performance of special education children at 7 and 9
      years of age].
AB  - Prospective longitudinal data from children at a school for learning disabled
      were obtained. Intelligence and language scores were assessed at first grade and
      two years later. The results of two samples from Erlangen and Munchen showed a
      high stability of the intelligence scores but less stability of the language
      scores. There were remarkable improvements in language comprehension. Expressive
      language had a constant lag compared with the test-standard of children of the
      same age; the articulation did improve as expected. The children from this
      special school still had problems with verbal short term memory.

PMID- 8559741
TI  - [Predisposition for violence in adolescence].
AB  - Uncontrolled aggressiveness, violence, and reckless behavior make up the contents
      of many myths of the 'real man'. For youths with unfavourable developmental
      conditions these myths are especially important. Two types of adolescents,
      willing use violence, with antisocial personality developments are illuminated
      with the help of psychoanalytic models of understanding; the borderline disorder
      on a low structure level and the mimicry development with its 'false' structure
      development, which often leads to a wrong diagnosis. With specific interactions
      with youths of both types in an inpatient setting, developmental processes are
      described which then often lead to the use of violence if effective interventions
      are not used enough. In closing pedagogic, social-therapeutic and
      psychotherapeutic strategies for dealing with such adolescents are discussed.

PMID- 8559740
TI  - [What is concealed behind nonspecific emotional disorders (F93.8/9)--a diagnostic
      comparison with reference to 4 diagnostic codes of ICD-10].
AB  - Psychiatric diagnoses of three patient groups attending a clinical service in
      1992 and 1993 were compared: children with rather inspecific diagnoses F93.8 and
      F93.9, children with specific diagnoses (f93.0 to F93.3 and children without
      psychiatric disorders. Data were gathered by the clinical documentation based on
      WHO recommendation. Result was a difference between the specific group and the
      inspecific group due to the psychopathological evidence. Further the variables of
      the fifth axis of MAS were analysed.

PMID- 8559742
TI  - ["Sceno-R": a revision of materials for the Sceno Test].
AB  - Von Staabs Scenomaterial, which was designed in the thirties, is in many parts
      obsolete and therefore only partially applicable, was critically examined, partly
      replaced, completed and new elements were added. The reasons for each piece were
      produced by the projective framework which von Staabs herself uses as a pretext.
      With the aid of the new material the possibilities of projections have been
      considerably extended and furthermore, they make areas like father-symbolization
      or modern media available, which were not available up to now.

PMID- 8559743
TI  - [Separation in the mother-son relationship: an adolescent problem in Rainer Maria
      Rilke's story "Silent accompaniment"].
AB  - The story 'Quiet Accompanying' by Ranier Maria Rilke's early work is of special
      interest for research on adolescence. The story is a literary contribution to the
      separation conflict of parents and their maturing children, especially the
      separation crisis in the mother-son relationship. The story's suspense is derived
      from the son's desire to begin a new phase in life and his experience of being
      powerless regarding his ties to his family. Thereby the adolescent crisis of the
      male main character is indirectly picked out as the main theme in the description
      of the mother's separation crisis. In the mother's 'dream' where the departure
      for a sunday excursion is described, an image of the son's adolescence with the
      components search for identity, separation and closeness develops. The son's
      efforts finally fail because mother and son are captured in their relationship
      characterized by conflicts and fears.

PMID- 8559744
TI  - [Indications for family therapy in university ambulatory psychotherapy].
AB  - Research about indications for family therapy is almost lacking. There are only
      few studies dealing with the issue which problem or which intrapsychic or
      interpersonal conflicts should be addressed by family therapy. Clinical decisions
      concerning family therapy should be based on empirical studies to get more
      knowledge about the criteria, in which case a specific modality of family therapy
      and/or a specific setting are indicated. The differential and adaptive indication
      process complements one another by means of the interaction of the therapist
      family system. Our study includes 67 decision making processes which took place
      at an university outpatient clinic. Our results show that the decisionmaking
      process is based on a selection of indications. The modality of treatment-
      individual or family therapy--run either in combination or in a sequence, is
      related to criteria with respect to the patient and his family. The style of
      application for psychotherapy--whether one family member is registering the
      family as a whole or the patient seeks help only for himself--makes the
      difference. The style of application seems to clear the way for the treatment
      suggested by the therapist.

PMID- 8559745
TI  - [Are "behaviorally disordered" migrant children of "noncompliant" parents
      treatable? Interdisciplinary cooperation between system-oriented school
      psychology and psychoanalytically oriented therapy].
AB  - This case presentation describes the cooperation between experts of different
      basic training and theoretical provenance. A system oriented school psychologist
      takes on the 'case' of a massively behaviourally abnormal, aggressive, and
      marginalized girl of working migrants from the lower stratum, prepares the way
      for psychotherapy and transfers the treatment to a psychoanalyst. In this case
      the role of the school psychologist consists of receiving a crisis situation
      which is slipping out of hand and redefining the problems with all parties
      involved. By expanding the perspective to the context of school-family
      immigration society contradictions and breaks become evident. The culture shock
      of the first migration phase was reinacted by the parents in the difficult
      confrontation with the Swiss institutions. In contrast to psychosocial sees the
      contradictions as being logical-congruent and tries to build bridges and activate
      change. The transformation of rigid reality constructs is furthered and
      psychotherapeutic treatment is mediated, explained and accompanied during the
      process. The role of the psychoanalyst consists of taking up the relationship to
      the girl and establishing a serviceable working relationship with the parents.
      She has to recognize the girl's inner and unconscious conflicts which are
      actualized in transference and countertransference in the therapeutic process.
      After empathetic interpretative work she offers new forms of dealing with
      conflicts which take the girl's outer reality (family, school, migrant situation,
      cultural reality) into consideration. Accompanying the parents intensively at the
      same time broadens their competence in raising their daughter. In this case the
      neurotic developmental disorder is strongly connected with the migration problem.

PMID- 8559746
TI  - [Borderline developmental disorders in children--on theory and treatment].
AB  - The author characterizes so called "borderline-children" on the basis of 190 case
      studies referring to the results of a survey of some 100 child therapists and 40
      child psychiatrists. "Borderline-children" show severe psycho-social strain and
      traumatic experiences and can be characterized by discrepant development,
      narcissistic pathology, aggressively and impulsiveness, clinging relationships as
      well as contact problems with children of the same age. The therapy aims at
      helping children to continue their development at a level appropriate to their
      age. Due to anxieties and hectic acting out, the therapy has to set distinct
      boundaries from the very beginning. Regression has to be curbed, archaic
      fantasies are to be copied with at a metaphorical level by play therapy and not
      interpreted by the therapist so that dissociated conscious matter is bridged.
      Usually the social environment has to be integrated into the treatment. In some
      cases. residential treatment and pharmacotherapy are necessary.

PMID- 8559747
TI  - [Social work in the child and adolescent psychiatric clinic--aspects of quality
      assurance within the scope of the psychiatric personnel regulation].
AB  - After defining social work in child and adolescent psychiatry as social therapy,
      we present the development of our own concept and our experiences, referring to
      the Psych-PV's professional provisions (Psych-PV being a law ruling the staff:
      patient ratios in FRG). Social work in the multiprofessional team contributes
      independently to therapy, and it unquestionably adds to the institutional
      perspectives.

PMID- 8559748
TI  - Evaluation of routine prenatal diagnosis by a registry of congenital anomalies.
AB  - Prenatal diagnosis performed by ultrasound scan is now a routine part of prenatal
      care in many countries. How many fetal anomalies are actually detected by these
      procedures? We have used our registry of congenital malformations to answer this
      question. In a previous study (Prenat. Diagn., 12, 263-270, 1992), considering
      the period 1979-1988, we have shown that prenatal diagnosis was performed in 23.1
      per cent of fetuses with a chromosomal aberration and in 20.1 per cent of fetuses
      with non-chromosomal anomalies. In 1991 and 1992, the percentage of termination
      for Down syndrome was 44.4 and 41.9 per cent, respectively. From 1989 to 1992,
      the detection rate and the specificity of prenatal diagnosis by ultrasonographic
      examination were improved. The detection rate for isolated malformations (fetuses
      with only one anomaly) and for multiple malformed children was 26.2 and 66.0 per
      cent, respectively. The detection rate of congenital anomalies by ultrasonography
      was variable for the different categories of malformation. A high detection rate
      was observed for anencephaly (100 per cent) and urinary tract malformation. A low
      detection rate was seen for cleft lip (17.5 per cent) and limb reduction defects
      (18.2 per cent).

PMID- 8559749
TI  - Prenatal diagnosis of fragile X syndrome: (CGG)n expansion and methylation of
      chorionic villus samples.
AB  - Fragile X syndrome is the most common form of inherited mental retardation, due
      to an expansion of the (CGG)n trinucleotide repeat in the FMR-1 gene and
      hypermethylation of its 5' upstream CpG island. Two major problems remain to be
      resolved for fragile X prenatal diagnosis: the abnormal methylation patterns of
      chorionic villus samples (CVS) and the inability to predict the mental status of
      females with the full mutation. We present here the results of ten prenatal
      diagnoses of fragile X syndrome using Southern blotting and polymerase chain
      reaction (PCR) amplification, and the analysis of 50 further CVS to test the
      methylation status of the CpG island of the FMR-1 gene. In the ten 'at-risk' CVS,
      eight normal (five males and three females) and two affected male fetuses were
      detected. Absence of methylation in the CVS was observed in two cases, which was
      not found upon subsequent examination of the newborn or of fetal tissues. In the
      50 CVS not 'at risk' for fragile X syndrome, abnormal fragment patterns for probe
      StB12.3 were detected in 32 per cent for female and 24 per cent for male fetuses.
      This abnormal pattern could be due to absent or partial methylation of the CpG
      island of the FMR-1 gene in chorionic villus tissues.

PMID- 8559750
TI  - Pregnancy outcome after transcervical CVS with a flexible biopsy forceps:
      evaluation of risk factors.
AB  - The pregnancy outcome of 1936 women who had transcervical chorionic villus
      sampling (CVS) with a flexible biopsy forceps was evaluated. Follow-up until 4
      weeks after delivery was 99.4 per cent. Various patient- and procedure-related
      risk factors for spontaneous loss (fetal or neonatal death) were analysed using
      stepwise logistic regression analysis. The overall spontaneous loss rate was 4.5
      per cent. Factors found to be significantly associated with spontaneous loss were
      quantity of villi < or = 15 mg (relative risk (RR) 2.13), a history of first
      trimester miscarriage (RR 1.87) or delivery between 16 and 27 weeks (RR 3.87),
      cervical culture positive for anaerobes (RR 4.52) or group B streptococcus (RR
      3.62), post-procedural bleeding > 3 days (RR 1.99), and multiple insertions (RR
      2.64). Significant differences in loss rates between individual operators were
      found. A learning effect was not present. There were no infants born with
      terminal transversal limb anomalies in our series. We conclude that knowledge
      about significant risk factors for spontaneous loss after CVS is important both
      for obstetricians carrying out CVS procedures and for women seeking prenatal
      diagnosis.

PMID- 8559751
TI  - Prenatal diagnostic testing for familial dysautonomia using linked genetic
      markers.
AB  - Familial dysautonomia (FD), a recessively inherited disease, has been mapped to
      chromosome 9q31. Highly polymorphic dinucleotide repeat markers flanking the
      genetic locus and at the same genetic location have been identified. We describe
      the prenatal diagnosis of FD using linkage and linkage disequilibrium analyses
      with these markers. Twelve families were analysed for informativeness and of
      these, seven went on to have prenatal testing (a total of eight fetuses tested).
      All of these fetuses were predicted to be heterozygous unaffected (FD carriers).
      Seven fetuses have come to term and are normal. In the absence of a recombinant
      proband, a panel of three proximal and three distal markers is sufficient to
      provide informative flanking markers and an 87-96 per cent likelihood of a highly
      predictive test. In an additional family at 1:4 risk for FD, no DNA was available
      from the propositus. This family was analysed using linkage disequilibrium to the
      #18 allele of the tightly linked marker D9S58 in conjunction with linkage
      analysis using data from two unaffected children. Prenatal diagnosis in this
      family indicated an affected fetus.

PMID- 8559752
TI  - Isolated fetal hydronephrosis: beware the effect of bladder filling.
AB  - The aim was to assess the role that fetal bladder size has in the determination
      of fetal hydronephrosis. Forty-three fetuses were evaluated for fetal
      hydronephrosis in the second trimester of pregnancy. Anteroposterior measurements
      of the renal pelvis were obtained with a full bladder and again when the bladder
      emptied in each fetus. Statistical analysis was performed using the Spearman rank
      order correlation coefficient to assess the relationship between bladder status
      and renal dilation. The anteroposterior size of the fetal renal pelvis diminished
      from 6.8 +/- 1.8 mm on a full bladder scan to 4.5 +/- 1.6 mm when the bladder was
      emptied (P < 0.001). Fifty-three per cent of the fetuses whose renal pelvic
      measurements were 5 mm or more on a full bladder scan had normal-appearing renal
      pelvises when their bladders emptied. The status of the fetal bladder should be
      considered when evaluating fetal hydronephrosis.

PMID- 8559753
TI  - Cross-hybridization of the chromosome 13/21 alpha satellite DNA probe to
      chromosome 22 in the prenatal screening of common chromosomal aneuploidies by
      FISH.
AB  - In a routine application of commercially available centromeric DNA probes for the
      prenatal screening of common trisomies involving the autosomes 13, 18, and 21,
      and sex chromosomes, four cases of discrepancy between fluorescence in situ
      hybridization (FISH) results and follow-up cytogenetic analysis were observed
      from a total of 516 cases of amniocentesis. In three of these cases, the results
      were false negative, and in one false positive. In this case, amniocentesis was
      performed because of a positive triple test in a 34-year-old woman with previous
      infertility treatment. The alpha satellite DNA probe for chromosomes 13/21
      revealed five signals in 50 per cent of uncultured amniocytes, while standard
      cytogenetic analysis showed a normal karyotype. FISH analysis on metaphase
      chromosomes demonstrated the location of the additional signal in the centromeric
      region of chromosome 22. This additional signal was also present in the
      centromeric region of chromosome 22 of the mother, providing evidence for a
      possible inherited polymorphism in chromosome 22 responsible for unspecific
      hybridization with the alpha satellite probe for chromosomes 13/21 in this case.
      The observed polymorphism in centromeric regions may contribute to unreliability
      of the use of the 13/21 alpha satellite probe for prenatal screening by FISH.

PMID- 8559754
TI  - Chromosome 18 analysis by fluorescence in situ hybridization (FISH) in human
      blastomeres of abnormal embryos after in vitro fertilization (IVF) attempt.
AB  - We performed fluorescence in situ hybridization (FISH) with a chromosome 18
      specific probe on human abnormal cleaved embryos, fertilized either by two
      spermatozoa and exhibiting three pronuclei (3 PN) or normally fertilized and
      exhibiting two pronuclei (2 PN) with subsequent severe fragmentation and/or
      blocking. The aim of the study was to evaluate the incidence of chromosome 18
      anomalies among these embryos in order to evaluate the FISH efficiency on such
      material and to obtain more precise and complete data than those obtained with
      classical cytogenetic analysis. For the 3 PN cleaved embryos, FISH confirmed the
      frequent regulation towards diploidy (25 per cent) and the high frequency of
      mosaics (53 per cent). For the 2 PN blocked or damaged embryos, FISH permitted
      chromosome evaluation, which was otherwise impossible with classical cytogenetic
      techniques: we also found a high mosaic frequency (45 per cent) with these
      embryos. If this frequency were the same for normally developing embryos, it
      would be a major obstacle to the reliability of either chromosomal or genetic
      preimplantation diagnosis.

PMID- 8559756
TI  - The prognostic factors in the prenatal diagnosis of the echogenic fetal lung.
AB  - The prenatal diagnosis of an echogenic fetal lung (EFL) is now often made in the
      early second trimester using high-resolution ultrasound. This ultrasound
      appearance is usually caused by a congenital cystic adenomatoid lung malformation
      (CCAM), an intrapulmonary lung sequestration or obstruction of a major airway. In
      order to provide prognostic guidelines to parents who may be considering
      termination of a fetus with these findings, we have analysed a series of 11 cases
      diagnosed in our centre over the past 2 years in conjunction with 60 cases from
      major published series. The data suggest that in the absence of non-immune
      hydrops fetalis (NIHF) or other anomalies, the outcome for the fetuses is
      excellent, with over 90 per cent survival. Neither early diagnosis (24 weeks) nor
      the presence of mediastinal shift is a poor prognostic indicator. In addition, it
      appears that if NIHF is absent at diagnosis, the chance that it will develop as
      the pregnancy continues is small (6 per cent). Furthermore, there is a
      significant (up to 30 per cent) chance that this ultrasound finding will resolve
      in utero. The development of in utero fetal surgical techniques may be the only
      hope for those hydropic fetuses who appear to have a dismal prognosis.

PMID- 8559755
TI  - Identification of a case of maternal uniparental disomy of chromosome 10
      associated with confined placental mosaicism.
AB  - We report a case of maternal uniparental disomy of chromosome 10 discovered after
      chorionic villus sampling (CVS). Direct preparations revealed mosaic trisomy 10,
      while cultured CVS cells, as well as amniotic fluid cells, showed only a normal
      46,XY complement. DNA analysis using microsatellite markers showed both
      chromosomes 10 to have been inherited from the mother. The pregnancy was
      complicated by polyhydramnios. A phenotypically normal male infant of appropriate
      size was delivered by Caesarean section at 41 weeks' gestation. Since only the
      direct preparations showed trisomy 10, this case illustrates the importance of
      CVS direct preparations in the detection of pregnancies at risk of uniparental
      disomy (UPD). Although the increased frequency of confined placental mosaicism
      (CPM) diagnosed when direct preparations are performed has been viewed
      negatively, identification of both CPM and UPD may have biological and clinical
      significance for a pregnancy. Even though only a single case of maternal disomy
      10 is reported here, the apparently normal phenotype provides evidence that there
      are no major imprinted loci on chromosome 10 that affect in utero growth and
      development. However, other potential effects such as mental retardation will
      require long-term follow-up of this as well as additional cases.

PMID- 8559757
TI  - Prenatal diagnosis of Smith-Lemli-Opitz syndrome is possible by measurement of 7
      dehydrocholesterol in amniotic fluid.
AB  - Amniocentesis was performed at 17.3 weeks in a pregnancy with severe intrauterine
      growth retardation. Cytogenetic studies on amniocytes were normal, 46,XX, and the
      pregnancy was continued. The diagnosis of Smith-Lemli-Opitz syndrome was
      suspected in the neonatal period and confirmed by the presence of 7
      dehydrocholesterol (7-DHC) in the plasma (0.4 mmol/l, normal = not detectable)
      associated with a low total cholesterol concentration (0.4 mmol/l, normal = 2.56
      +/- 0.23). Retrospective analysis of the amniotic fluid sample revealed an
      elevated level of 7-DHC (0.022 mmol/l; normal = undetectable). Therefore
      measurement of 7-DHC levels in amniotic fluid during the second trimester of
      pregnancy is useful for the prenatal diagnosis of Smith-Lemli-Opitz syndrome in
      families at risk and should be considered in cases of severe growth retardation
      of unknown aetiology for which amniotic fluid is available and in which a normal
      chromosomal pattern in amniocytes is present.

PMID- 8559758
TI  - Non-immunological hydrops fetalis and intrapericardial teratoma: case report and
      review.
AB  - A large intrapericardial teratoma was found at necropsy in a 38-week stillborn
      fetus, in which prenatal diagnosis of hydrops fetalis and an echogenic cardiac
      mass had been made. Clinical and pathological data are reported. In utero
      intrapericardial teratomata lead to different outcomes depending on whether fetal
      hydrops is associated. When generalized fetal hydrops is not present, the outcome
      is good, even in cases with large pericardial effusions. When generalized fetal
      hydrops occurs, it often results in a poor outcome. In our literature review, we
      have found eight perinatal deaths in nine similar cases reported.

PMID- 8559759
TI  - Fetal ascites and oligohydramnios: prenatal diagnosis of a sialic acid storage
      disease (index case).
AB  - In a 20-year-old primiparous patient, a routine ultrasound scan performed at 28
      weeks revealed fetal ascites, bilateral talipes, and oligohydramnios. This woman,
      married to possibly her first cousin, was at risk for an autosomal recessive
      disease, a metabolic disorder. At 29 weeks, an amniotic fluid biochemical study
      revealed the presence of an abnormal band of free sialic acid, leading to a
      diagnosis of a congenital form of sialic acid storage disease. Termination of
      pregnancy was performed at 30 weeks. Measurement of free sialic acid in cultured
      fetal skin fibroblasts confirmed the diagnosis.

PMID- 8559760
TI  - Prenatal sonographic diagnosis of autosomal recessive polycystic kidney disease
      (ARPKD) during the early second trimester.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is a rare hereditary
      disease with a high neonatal mortality. Currently, prenatal diagnosis is possible
      only during the second half of pregnancy, when bilaterally enlarged, echogenic
      kidneys are visible by ultrasound. We describe a case in which a diagnosis of
      ARPKD was sought in the first half of pregnancy. High-resolution ultrasonography
      revealed echogenic, normal-sized kidneys at 15 + 4 weeks. Microsatellite DNA
      analysis of a chorionic villus sample, parental blood, and blood of an affected
      sibling showed that the fetus had the maternal haplotype and a recombination of
      the paternal haplotype. Thus, no distinction between homo- and heterozygosity for
      the ARPKD mutation in the fetus was possible. A further ultrasound examination at
      19 + 4 weeks confirmed the previous results, indicating that the fetus was likely
      to be affected. After termination of the pregnancy, the diagnosis was confirmed
      on microscopic examination.

PMID- 8559761
TI  - Prenatal diagnosis of ring chromosome 6.
AB  - An amniocentesis was performed on a gravida 1, para 0 23-year-old female because
      of high maternal serum alpha-fetoprotein and nuchal thickening/cystic mass
      apparent on the fetal ultrasound. Detailed ultrasound examination revealed
      multiple anomalies including brain abnormalities. The fetus was found to have a
      mosaic female karyotype: 45,XX, - 6/46,XX,r(6) (p25q27) (62 per cent:38 per
      cent). This is the first report of a prenatally diagnosed case of ring chromosome
      6.

PMID- 8559762
TI  - Cholecystomegaly and fetal gallstones.

PMID- 8559763
TI  - The origin of ascites in prune belly syndrome--early sonographic evidence.

PMID- 8559764
TI  - Postnatally confirmed trisomy 16 mosaicism: follow-up on a previously reported
      patient.

PMID- 8559765
TI  - Posting maternal blood samples for free beta-human chorionic gonadotrophin
      testing.

PMID- 8559766
TI  - Current awareness in prenatal diagnosis.

PMID- 8559767
TI  - 19th Symposium of the Association of Neuropsychopharmacology and
      Pharmacopsychiatry (AGNP). Nuremberg, October 4-7, 1995. Abstracts.

PMID- 8559768
TI  - World Congress on Medical Physics and Biomedical Engineering. Rio de Janeiro,
      Brazil, 21-26 August 1994. Abstracts. Part 1.

PMID- 8559769
TI  - World Congress on Medical Physics and Biomedical Engineering. Rio de Janeiro,
      Brazil, 21-26 August 1994. Abstracts. Part 2.

PMID- 8559770
TI  - Sexual responses to urinary chemosignals depend on photoperiod in a male primate.
AB  - In male lesser mouse lemurs, testicular size and plasma testosterone levels are
      controlled by photoperiodic variations but can be modified by urinary cues from
      conspecifics. To test whether urinary cues may have differential effects on
      testicular size and testosterone levels depending on the photoperiodic state of
      the receiver, isolated males were exposed for 4 wk to urinary cues from oestrous
      females or dominant males:--at the beginning of the breeding season induced by
      long photoperiod (LD),--during refractoriness to LD leading to spontaneous sexual
      regression and during sexual quiescence exhibited by males kept in short
      photoperiod (SD). Urinary chemosignals from females were always stimulatory
      producing significant increases in testosterone levels. By contrast, urinary cues
      from dominant males produced significant differential effects on reproductive
      function. They depressed sexual function only at the beginning of the breeding
      season. During SD or during refractoriness to LD, chemosignals were stimulatory
      leading to increases in testosterone levels and full development of testes. These
      results demonstrate that the same chemosignal may have opposite effect on sexual
      function of the receiver depending on endocrine mechanisms set up by photoperiod.

PMID- 8559771
TI  - Diel rhythms of feeding activity in the European catfish, Silurus glanis.
AB  - The diel rhythms of feeding activity of S. glanis held singly or in groups, and
      with free or time-restricted access to self-feeders is described. It was found
      that this this species has a strongly nocturnal feeding activity. European
      catfish can be trained to feed itself by day, but in such case its voluntary feed
      intake is reduced. When trained to feed by day, they resume their nocturnal
      behavior in less than 24 h when they have again free access to feed. It is also
      clearly evidenced that this fish species does not behave the same way when it is
      isolated from its congeneres rather than when it is maintained in groups, with a
      tendency to become arhythmic.

PMID- 8559772
TI  - Short days increase sensitivity to methadone inhibition of male copulatory
      behavior.
AB  - Exposure to short, winter-like daylengths produces deficits in male golden
      hamster copulatory behavior, even when exogenous testosterone is administered to
      replicate serum concentrations typical of hamsters housed in long days. Daylength
      also regulates opiate receptor concentrations in limbic brain regions which
      control sexual behavior, and the response of gonadotropin secretion to opiate
      receptor antagonists is modulated by daylength. This study tests the hypothesis
      that short days amplify the opiatergic inhibition of copulatory behavior. Male
      golden hamsters were castrated and given testosterone implants before transfer to
      short days. Hamsters were tested for copulatory behavior after injections of
      saline or various doses of methadone, an opiate agonist believed to be specific
      for mu receptors. Locomotor activity was also measured. Hamsters housed in short
      days showed copulatory deficits in response to lower doses of methadone than
      hamsters housed in long days. Short days enhanced copulatory deficits after
      methadone at doses which did not affect general activity.

PMID- 8559773
TI  - An analysis of factors that induce hibernation in Syrian hamsters.
AB  - Factors that induce hibernation of Syrian hamsters were analyzed in young adults
      and older adults under two photoperiodic conditions (i.e., a long photoperiod and
      a natural photoperiod). The experiment was performed from September 1st, 1992 to
      March 24th, 1993. The older hamsters entered earlier into and spent longer in
      hibernation than the young ones. Water deprivation caused more torpor than free
      access to water in the older hamsters as well as in the young ones. As the
      ambient temperature dropped, not only the number of animals entering hibernation
      but also the number of days in hibernation increased. Long photoperiod in the
      cold environment tended to induce torpor in the older animals but not in the
      young ones. An examination of testicular weight at the end of the experiment
      revealed that the regressed testes were well correlated with the induction and
      maintenance of hibernation regardless of age and photoperiod.

PMID- 8559774
TI  - Effects of diencephalic lesions on approach responses and color preferences in
      quail.
AB  - The effects of stereotaxic radio-frequency lesions on artificially selected
      approach responses and artificially selected or imprinted red or blue preferences
      were studied in Japanese quail chicks. No effects were found from lesions in
      anterior preoptic or pretectal areas and only slight attenuation of red
      preferences by lesions in nucleus rotundus, opticus principalis thalami and
      geniculatus lateralis pars ventralis. Extensive lesions in medial diencephalic
      and bordering areas of telencephalon, ansa lenticularis, lateral and medial
      forebrain bundle diminished approach tendencies and greatly attenuated the
      genetically influenced red preferences. Medial diencephalic lesions confined to
      the dorsomedial thalamic complex and lateral hypothalamus left approach
      tendencies intact but similarly attenuated only red preferences. Imprinted red or
      blue preferences of a highly imprintable quail line were also attenuated; red
      preference strongly, blue preference moderately. The data indicate differential
      diencephalic mediation of the quail's genetically distinct color preferences and
      suggest diverse subtelencephalic channels for mediation of approach responses and
      stimulus preferences. The results also suggest common neural mediation of
      genetically determined and acquired stimulus preferences.

PMID- 8559775
TI  - Nest defense and survival of offspring in highly aggressive wild Canadian female
      house mice.
AB  - Nest defense behavior was examined in wild female house mice (Mus domesticus)
      that were derived from a stock initially trapped in Alberta, Canada. The first
      objective was to determine whether behavior toward pups prior to mating was
      related to the intensity of postpartum aggression in a variety of social
      situations. Therefore, prior to the experiments we screened virgin females for
      their behavior toward a newborn pup [60% of the females exhibited infanticide and
      40% were noninfanticidal: 7% were parental (retrieved and hovered over the pup)
      and 33% ignored the pup]. Infanticidal and noninfanticidal females were then
      mated with males and used in four experiments. In Experiment 1 the females were
      housed individually prior to deliver, while in Experiment 2 the females were
      allowed to remain with their mates; in both situations all females successfully
      reared litters of similar sizes. Male and female intruders (that had all
      exhibited infanticide when previously tested with a pup) were placed separately
      into a test cage containing a lactating female during the first four days after
      delivery. Regardless of the presence of the stud male, previously infanticidal
      females were more aggressive (exhibited more attacks per min) toward both male
      and female intruders than were previously noninfanticidal females; infanticidal
      females also exhibited more of both forms of attack (offensive and defensive) and
      also attacked with greater intensity than did noninfanticidal females. The number
      of attacks toward intruders of both sexes increased for both infanticidal and
      noninfanticidal females between Day 1-4 postpartum, but very high rates of attack
      were observed on all days by the lactating females, including the day of
      delivery. In Experiments 3 and 4 only the most aggressive (previously
      infanticidal) females were tested. In Experiment 3, two unrelated, unfamiliar
      females were mated separately and then were housed together just prior to
      delivery, which was planned to occur 3-4 days apart. In 5 of the 15 cages, all
      pups disappeared on the day of delivery of the second female to deliver her
      litter. In the remaining 10 cages, it appeared that none of the pups produced by
      the 20 females were killed. Thus, in this experiment, 66% of pups survived to Day
      4 postpartum. In Experiment 4, two previously infanticidal female siblings, which
      had been housed together since birth, were placed together with a stud male. In
      all 9 cages only one female became pregnant and delivered pups, but only 3
      litters survived to Day 4 (no litters were observed being attacked during
      intruder tests).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8559776
TI  - Circadian activity rhythms in the solitary cape molerat (Georychus capensis:
      bathyergidae) with some evidence of splitting.
AB  - Circadian activity patterns were measured in the solitary, subterranean Cape
      molerat, Georychus capensis, under fixed 12:12 LD, constant dark DD, and constant
      light LL photoperiods for 250 consecutive days using passive infra-red activity
      sensors. The molerats displayed significant nocturnal activity rhythms under
      12:12 LD and free-running rhythms (23.5 h < tau > 25.8 h) under constant
      conditions. In one individual evidence was found of splitting of the activity
      rhythm under constant dark; the split rhythms free-ran with short- and long
      periods of 23.6 h and 24.7 h, respectively. These data show that, despite
      degenerate retinae, G. capensis (i) are capable of perceiving light at the level
      of the circadian pacemaker; (ii) can entrain endogenous activity oscillators to
      fixed photoperiods; and (iii) display evidence of a free-running activity
      oscillator.

PMID- 8559777
TI  - A comparison of rats and mice in a swimming pool place task and matching to place
      task: some surprising differences.
AB  - An ecological niche that requires competency in water has prepared rats for the
      swimming pool spatial tasks that they are administered in the laboratory. Their
      ability to eventually solve spatial tasks in a single trial makes them ideal
      subjects for evaluating neural contributions to spatial behavior and for
      addressing many other neuroscience problems. Swimming pool place tasks are also
      given to mice, but the spatial abilities of the animal has not been evaluated as
      extensively as have those of rats. In the present paper, place learning in a
      single place task and a matching to place task is comparatively assessed in
      groups of rats and mice. The rats were superior to the mice on both problems.
      Although the mice could learn a single place problem, their acquisition was
      slower and their asymptotic performance was inferior to that of rats. Mice also
      did not display one trial learning on the matching to place task as did rats.
      These species differences in swimming pool place learning are discussed with
      respect to both methodological considerations and to species differences in
      preparedness to learn. It is suggested that given the variability of the
      performance of mice across both strains and laboratories, rat performance could
      be used to provide a baseline for comparative purposes.

PMID- 8559778
TI  - PTZ-kindling after colchicine lesion in the dentate gyrus of the rat hippocampus.
AB  - Pentylenetetrazol (PTZ)-kindling represents a model of a primarily generalized
      epilepsy. We investigated the role of the dentate gyrus of the hippocampus in
      this model of epilepsy by destruction of this structure by colchicine, injected
      in the dorsal and ventral hippocampus of rats. After a period of 7 days PTZ
      kindling was started. The kindling development was slightly accelerated in
      colchicine treated animals compared to control rats. After kindling completion
      the learning performance of the rats was tested in a shuttle-box experiment. The
      learning deficit found in fully kindled rats was not influenced by colchicine
      pretreatment. However, colchicine itself impaired the learning performance of
      rats in the shuttle-box.

PMID- 8559779
TI  - Effects of the menstrual cycle on dressing behavior in the cold.
AB  - The purpose of the present study was to determine the effect of the menstrual
      cycle on dressing behavior in cold exposure. Rectal and skin temperatures,
      temperature sensation and metabolic rate were measured in seven women during the
      luteal (L) and the follicular (F) phases of the menstrual cycle, as was their
      dressing behavior in these two phases. The subjects were instructed to dress so
      as to feel comfortable when the ambient temperature was decreased from 30 degrees
      C to 15 degrees C (07:00-09:00). Most subjects dressed more quickly and with
      thicker clothing in the L phase. They felt cooler in the L phase during the last
      30 min of the temperature fall. Rectal and skin temperatures showed significant
      differences between L and F phases and metabolic rate was significantly higher in
      the L phase. The results can be interpreted in terms of the establishment of a
      higher set-point in core temperature during the L phase.

PMID- 8559780
TI  - Light-dark and food restriction cycles in sea bass: effect of conflicting
      zeitgebers on demand-feeding rhythms.
AB  - Sea bass, a fish species characterized by its dualistic feeding pattern, was
      investigated to study the synchronizing effect of light and food on the demand
      feeding rhythm. Nocturnal and diurnal sea bass, both in groups and individually,
      were exposed to restricted-feeding (RF) and light-dark (LD) cycles of different
      periods. The phase relationship between both zeitgebers was also studied. The
      results show that food-demand rhythms synchronize to periodic food availability
      under constant light conditions (DD) and that there is a partial coupling between
      food-entrained and light-entrained activity under conflicting zeitgebers (LD
      13:13 h and RF 4:20 h), suggesting the existence of a feeding entrainable
      oscillator (FEO) in addition to the master light entrainable oscillator (LEO). In
      some cases, food availability restricted to the light or dark phase contrary to
      that of the previous feeding phase changed a diurnal feeding pattern into
      nocturnal and viceversa, suggesting that food can be one of the switching factors
      that decides whether the circadian system of sea bass is nocturnal or diurnal.
      However, the fact that the feeding pattern of some fish was unrelated with the
      phase in which food was available suggests that other internal and/or external
      factors could be involved in the temporal flexibility of sea bass.

PMID- 8559781
TI  - Effect of ovarian steroids on footshock avoidance learning and retention in
      female mice.
AB  - Mice were trained to avoid footshock in a T-maze, with retention tested one week
      later. Adult male CD-1 mice made their first avoidance during acquisition after
      fewer trials than random cycling females and with less variability. Female mice
      in diestrus, when plasma levels of progesterone are low, learned to avoid
      footshock faster than females in estrus. Ovariectomized (OVX) mice learned in
      fewer trials than intact random cycling mice. Similar differences, though of a
      smaller magnitude, were found on the retention tests (i.e. males had better
      retention than females, mice in diestrus showed better retention 8 days later
      when in the same part of the estrous cycle than those in estrus, and OVX mice had
      better retention than cycling females). OVX mice with estrogen implants learned
      faster than those with progesterone implants or progesterone plus estrogen
      implants. Hormonal status did not affect sensitivity to acoustic or footshock
      stimuli as measured by a startle reflex, nor did it affect activity. Pretraining
      administration of amphetamine, picrotoxin and strychnine attenuated the impairing
      effect of progesterone on acquisition. The possibility that progesterone may
      impair learning and to some extent, retention by facilitating the GABAergic
      activity and thereby reducing arousal level is discussed.

PMID- 8559782
TI  - Dopaminergic neurons in the zona incerta modulates ingestive behavior in rats.
AB  - The zona incerta, located in the ventral thalamus, is a site of convergence of
      signals related to drinking. In the present experiments, agonists and antagonists
      of dopamine receptors were injected into the ZI of animals deprived of water
      overnight. Injection of 53 nM dopamine or the D2 dopamine receptor agonist PPHT
      caused a reduction of water and food intake, while the injection of the D1
      receptor agonist SKF38393 had no effect. The current results suggest that
      dopamine injected into the ZI exerts inhibitory influences on drinking behavior
      mediated by D2 type receptor.

PMID- 8559783
TI  - Effect of peptide YY (PYY) on food-associated conflict.
AB  - Peptide YY (PYY) administered centrally in rats induces powerful overeating. PYY
      also occurs endogenously in humans and is elevated in abstaining bulimic
      patients. To examine the effect of PYY in an environment that parallels some
      aspects of bulimia, rats were tested in a paradigm associated with approach
      avoidance behavior, choosing a preferred (sweet) food paired with shock, over
      regular food safe from shock. PYY-treated rats chose to sustain shock to retrieve
      and consume the preferred food, at a significantly greater speed and quantity.
      The number of approaches that were met without retrieval of food due to anxiety
      after PYY treatment indicates that PYY increased motivation towards feeding,
      rather than anxiolysis. This effect of PYY in a model of conflict associated with
      food choice resembles aspects of bulimic binge-eating, which is characterized by
      the repetitive, rapid intake of food, despite anxiety associated with this
      behavior.

PMID- 8559784
TI  - Potentiation of the immobility response elicited by bandaging and clamping in
      mesencephalic rats.
AB  - In earlier work, we showed that adult rats exhibit immobility response (IR) if a
      clamp is fastened to the skin of the nape of the neck, but not at other areas of
      the body, and not by bandaging. The present study characterizes IR in adult rats
      with complete mesencephalic transections. In the mesencephalic rats, the duration
      of the IR not only increased, but the stimuli capable of eliciting it were more
      diverse. All head and body areas clamped or bandaged were capable of inducing a
      profound IR. In contrast, the IR in intact rats was of shorter duration, and was
      only induced by clamping the neck, or by bandaging the upper or the lower torso.
      Furthermore, unlike the mesencephalic rats the ability of the bandaging to induce
      IR is reduced after the first trial and finally disappears. Only clamping the
      neck was able to persistently induce IR in intact rats. These data support the
      hypothesis that the IR control system is in the midbrain, hindbrain or spinal
      cord, and that systems above the mesencephalon modulate the IR. Such modulation
      appears to involve the ability to discriminate amongst tactile stimuli, and to
      integrate previous experience.

PMID- 8559785
TI  - Effects of electromagnetic fields and gender on neurotransmitters and amino acids
      in rats.
AB  - Epidemiological studies have linked electromagnetic field (EMF) exposure to
      certain forms of cancer, however only limited laboratory evidence supports a
      connection between EMF and biological effects. In the present study we exposed
      male and female rats to low level, 1000 milli-Gauss (mGs), direct current EMF
      generated with Helmholtz coils for 1 mo or 4 mo. The effects of these EMF
      exposures on regional brain neurotransmitter metabolism and circulating amino
      acid concentrations were determined. After 1 mo of EMF exposure the concentration
      of serotonin was elevated in the hypothalamus of male rats. Levels of the
      dopamine metabolite, 3-methoxytyramine, were increased in the corpus striatum of
      male and female rats that were exposed to EMF for 1 mo. Hypothalamic
      concentration of norepinephrine was elevated in both groups of male rats, as
      compared to respective female groups, but was not affected by EMF. Similarly,
      levels of tyrosine were increased in hypothalamus, corpus striatum and nucleus
      accumbens of male rats, but were not affected by EMF exposure. Following 4 mo of
      EMF exposure, no significant effect of EMF was observed. Significant sex
      differences in plasma amino acid concentrations were observed in both studies,
      with female rats exhibiting decreases in a majority of the amino acids measured.
      These results are suggestive that short-term exposure may cause small alterations
      in neurotransmitter metabolism and in circulating amino acids, which dissipate
      when exposure duration is increased.

PMID- 8559786
TI  - Effect of dexfenfluramine on metabolic and neurochemical measures in restraint
      stressed ob/ob mice.
AB  - Genetically obese (ob/ob) and lean C57BL/6J mice were subjected to 1 h acute
      restraint stress, and the effects on plasma glucose and corticosterone, and brain
      amines, were assessed relative to nonrestrained groups. Some mice were treated
      with dexfenfluramine (DFEN) prior to restraint. Compared with their lean
      counterparts, ob/ob mice had elevated basal plasma levels of both glucose and
      corticosterone. Both lean and ob/ob showed comparable absolute restraint-induced
      increments in these measures, but the fractional increase was much smaller in
      ob/ob. Metabolism of NE, DA and 5-HT was also assessed from the ratio of the
      metabolite-to-amine in various brain regions. Obese mice had smaller restraint
      related increases in monoamine metabolism than lean their counterparts. Acute
      DFEN increased corticosterone, but tended to reduce the restraint-induced
      elevations in glucose and monoamine metabolism.

PMID- 8559787
TI  - Central insulin enhances sensitivity to cholecystokinin.
AB  - Insulin acts in the brain to reduce food intake and body weight. Cholecystokinin
      (CCK) reduces meal size when administered peripherally. The purpose of these
      experiments was to examine their interaction. In Experiment 1, Long-Evans rats
      were infused with vehicle or insulin at doses from 0.5 to 2.0 mU/day into the
      third cerebral ventricles. Doses of 1.0 mU/day and higher caused reduced body
      weight. A dose of 0.5 mU/day was therefore taken to be subthreshold. In
      Experiment 2, rats receiving 0.5 mU/day of insulin intracerebroventricularly had
      greater suppression of 30-min meal size in response to intraperitoneal CCK-8 at
      doses from 0.25 to 8 mg/kg than did rats receiving intracerebroventricular
      saline. By itself, the insulin had no effect on body weight or meal size.
      However, a change of sensitivity to CCK by control rats over the course of the
      experiment clouded the interpretation. A third experiment was therefore conducted
      in which rats received an acute intracerebroventricular injection of insulin (0.1
      mU) or saline 1 h prior to a 30-min meal, and IP CCK-8 (4 mg/kg) or saline
      immediately prior to the meal. As in Experiment 2, insulin, itself, had no effect
      on meal size but enhanced the anorexic effect of CCK. These results are
      consistent with the hypothesis that central insulin acts by altering sensitivity
      to satiety agents.

PMID- 8559788
TI  - Spontaneous behavior and body temperature in male Central American Agoutis
      (Dasyprocta punctata) under different social conditions.
AB  - Pair-bonded males did not change rhythmic or phasic components of body
      temperature and motoric or behavioral activity with changing situations. Non pair
      bonded males displayed lowered oscillations of body temperature and decreased
      motoric activity, those living with a male under established conditions and those
      living with a female under changed conditions. Non pair-bonded males exhibited
      distinct changes in amounts of at least one of behavioral elements (scrapemark,
      scentmark, bury and scrape; indicating elevated sympathetic arousal) with
      changing situations. Variations in motoric activity and amounts of these
      behavioral elements were correlated with variations in rhythmic and phasic
      components of body temperature. For the regulation of arousal the results suggest
      a balance between behavioral and physiological activity effecting body
      temperature. The efforts for this regulation depend on the social situation of
      the animal.

PMID- 8559789
TI  - Combined effects of caffeine and malnutrition on the development of the
      trigeminal nuclear center: autoradiographic and biochemical studies.
AB  - Six groups of pregnant dams were each fed a 20%, 12%, and 6% protein diet with
      and without caffeine (2 mg/100 g b.wt), starting on day 7 of gestation. Dams of
      each group were injected with two successive daily doses of 3H-thymidine in an
      overlapping series beginning on day 7 and ending on day 16 of gestation. At day
      15 postbirth, brains of the offspring were removed, fixed and embedded.
      Neurogenesis in the rat trigeminal motor nucleus was examined by radiogram in
      serial sections. In general, the peak production of the neurons of the motor
      nucleus of V in the malnourished group of the control was on embryonic (E) days
      E10 + 11, whereas that of the caffeine group was E11 + 12. In the normally
      nourished group, peak production in the control was E9 + 10, whereas in the
      caffeine group it was E11 + 12. Trigeminal areas from the brains of pups of each
      group, which were kept frozen from our previous studies on suckling behavior
      (23), were used to analyze DNA, protein and cholesterol levels in the present
      study. At day 1 caffeine's effects on DNA, protein and cholesterol concentrations
      of the trigeminal area between the groups were different, depending upon the
      nutritional status. At day 15, those parameters in the caffeine group were
      greater although no caffeine was added to the lactating dams' diet. This study
      again demonstrated that prenatal caffeine intake in combination with protein
      energy malnutrition produces permanent effects on the trigeminal nuclear center
      indicated by autoradiography and changes in biochemical parameters.

PMID- 8559790
TI  - Oxygen consumption and body temperature rhythms in the golden spiny mouse:
      responses to changes in day length.
AB  - The golden spiny mouse Acomys russatus is a rock dwelling rodent which lives in
      extremely arid and hot habitats. In Israel it is nocturnal except in areas in
      which it coexists with the common spiny mouse A. cahirinus. In such places it is
      diurnal. The daily rhythms of body temperature (Tb) and oxygen consumption (VO2)
      were compared in mice acclimated to two different photoperiod regimes in the
      laboratory: 8L:16D (short day) and 16L:8D (long day) at a constant ambient
      temperature. The daily rhythms of VO2 and of Tb in A. russatus were found to
      differ greatly under long and short photoperiod. Both parameters peaked at lights
      out under both photoperiod regimes. In short day acclimated mice the effect of
      transmitter implantation was also studied. VO2 values at night were lower after
      implanting. The results of this study show that Tb and VO2 rhythms are altered by
      the lighting regimes. Seasonal acclimatization of thermoregulatory mechanisms in
      the golden spiny mouse are partly induced by changes in photoperiodicity.

PMID- 8559791
TI  - Influence of different light intensities during the daytime on evening dressing
      behavior in the cold.
AB  - The primary purpose of this study was to determine the effect of bright light
      exposure during the daytime on dressing behavior in the cold. Seven female
      volunteers were exposed to bright light of 4,000 lx ("Bright") or dim light of 10
      lx ("Dim") from 10 h to 18 h, complete darkness during the sleep period (22:30 h
      06:00 h), and 10 lx for the rest of the time. The subjects were instructed to
      dress to remain comfortable when the ambient temperature was decreased from 30
      degrees to 15 degrees C (20:30 h-22:30 h). Most subjects dressed more quickly and
      with thicker clothing in the Dim condition and felt cooler during the last 30 min
      of the temperature fall. The rectal temperature showed clear circadian rhythm
      both under Bright and Dim conditions, but it was significantly lower during sleep
      in the Bright condition. It is suggested that the set-point of core temperature
      is reduced at night during the Bright condition.

PMID- 8559792
TI  - Interaction of male sensory cues and estradiol in the induction of estrus in the
      prairie vole.
AB  - In the prairie vole, estrus and ovulation are induced by stimulation from a male,
      which also increases the female's gonadal weight and serum estradiol level. It is
      not known whether the induction of receptivity is dependent solely on an
      endogenous increase in circulating estradiol or an interaction of increased
      estradiol and male sensory stimulation. Using a dose response paradigm, we
      examined if a dose of estradiol within physiological range was sufficient to
      induce receptivity. We also examined if extended male contact could induce
      receptivity in ovariectomized females tested either without estradiol replacement
      or with a subthreshold dose of estradiol. We found that elevating blood levels of
      estradiol to those found during estrus was sufficient to induce sexual
      receptivity; male contact was not necessary. Extended male cohabitation did
      induce estrus in ovariectomized females treated with a subthreshold dose of
      estradiol, a dose which without male contact did not support sexual receptivity.
      In these same females, the extended male contact elevated circulating estradiol
      levels; the source of the estradiol is unknown.

PMID- 8559793
TI  - Opioid modulation of sucrose intake in CD-1 mice: effects of gender and housing
      conditions.
AB  - The effects of naltrexone (1 mg/kg, sc.) on consumption of a 5% sucrose solution
      were observed in nondeprived adult female CD-1 mice and in male mice. Males were
      either individually housed or were housed in pairs. Naltrexone significantly
      reduced the consumption of the sucrose in both female and male mice; in the case
      of the males the administration of naltrexone produced an intake pattern
      identical to that obtained for a less palatable (1.5%) sucrose solution in
      control conditions. There was no difference between subordinate and dominant
      males, neither in sucrose intake nor in the response to the naltrexone treatment.
      In a second experiment, it was shown that switching from a 5% to a 10% solution
      was sufficient to overcome naltrexone's suppressant effect in female mice,
      conversely this was not seen in the males. In general, the data are consistent
      with the view that opioid antagonists reduce effective palatability of sweet
      sucrose solutions in mice. There was no evidence that social isolation and stress
      related to subordination affected male mice's sucrose intake and response to the
      naltrexone challenge.

PMID- 8559794
TI  - Immunosuppressive treatment prevents behavioral deficit in autoimmune MRL-lpr
      mice.
AB  - MRL-lpr mice, which develop severe autoimmune disease, explore novel objects less
      well than do their congenic MRL(-)+/+ controls, in which symptoms of the disease
      are relatively mild. Moreover, diminished exploration in MRL-lpr mice correlates
      with the elevated titers of antinuclear antibodies (ANA) in their sera,
      suggesting that this behavioral deficit is caused by the autoimmune process. To
      test the hypothesis that autoimmunity affects behavior, in this study we examine
      whether treatment of the autoimmune process will reduce the difference in
      performance between the two MRL substrains in the novel-object test. Forty mice
      in each substrain were treated from 4 to 10 wk of age with the immunosuppressive
      drug, cyclophosphamide (100 mg/kg/wk, IP) or a saline vehicle. The
      immunosuppressive treatment reduced ANA titers to low levels and eliminated ANA
      production completely in 55% of MRL-lpr mice, suggesting an attenuation of the
      autoimmune process. In addition, treatment with cyclophosphamide, but not saline,
      abolished significant differences in exploration between the MRL-lpr and MRL +/+
      groups, as measured by the latency to touch a novel object and the time spent
      exploring it. Thus, the present results suggest that a treatment which
      ameliorates autoimmune symptoms can concurrently remove the substrain difference
      in behavior. The effect of cyclophosphamide in the MRL-lpr group is believed to
      reflect the suppression of pathogenic immune factor(s) that alter behavior during
      the onset of autoimmune disease.

PMID- 8559795
TI  - Effects of novelty and conditioned fear on small intestinal and colonic motility
      and behaviour in the rat.
AB  - Novelty and conditioned fear were used to investigate the effects of
      psychological stress on fasting small intestinal and colonic myoelectric activity
      and their relation with behaviour in freely moving rats fitted with bipolar
      electrodes on proximal jejunum and colon. Rats in both novelty and conditioned
      fear groups spent a 15 min session in a novel box, where only rats in the fear
      group received unescapable, repeated foot shock (10 x 6 s, 0.5 mA). Behaviour in
      groups reexposed to the box on day 1 or day 7 indicated a profound difference in
      emotional state. Conditioned fear rats remained largely immobile, while novelty
      rats displayed active exploratory behaviour. Behaviour during conditioned fear
      did not differ significantly between rats reexposed to the box either 1 or 7 days
      after foot shock, while novelty animals appeared more aroused on day 7.
      Conditioned fear on day 1 caused a significant increase in colonic spike burst
      frequency compared to basal values in the home cage. A smaller but significant
      increase was found in novelty rats. In groups tested after 7 days, both novelty
      and conditioned fear resulted in small increases in colonic burst frequency that
      did not differ significantly from each other. No effects were found on the
      incidence of the fasting jejunal Migrating Motility Complex. Defecation was see
      only in conditioned fear rats, but did not differ quantitatively between day 1
      and day 7. We conclude that, in the rat, colonic myoelectric spike burst activity
      is highly responsive to psychological stress, while the fasting pattern of small
      intestinal activity is more resistant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8559796
TI  - Measurement of physiological parameters and activity in a Mongolian gerbil during
      gravidity and lactation with an implanted transmitter.
AB  - This communication reports the first use of a transmitter implanted into the
      abdominal cavity of a small pregnant rodent to simultaneously measure the heart
      rate, core body temperature and general locomotory activity with no apparent side
      effects to the animals. Using this method the heart rate of one female Mongolian
      gerbil (Meriones unguiculatus) decreased from a mean of 303 +/- 6 (SE) (beats per
      minute) during gravidity to a level of 248 +/- 3 (SE) (beats per minute) during
      lactation. At the same time, the core body temperature increased from 37.7 +/-
      0.05 (SE) degrees C to 38.0 +/- 0.03 (SE) degrees C. During pregnancy the general
      locomotory activity of this female followed the normal nocturnal pattern for this
      species (i.e., greater activity during the dark period) but there was an overall
      reduction in activity to 85% of the nonpregnant state. The level of activity was
      further reduced during lactation to about 43% of the nonpregnant state. This was
      largely the result of less activity during the dark period so that activity in
      the dark period and light period became more or less equivalent.

PMID- 8559797
TI  - Retention of rotationally induced taste aversions.
AB  - Retention interval effects are seen in single-element taste-aversion learning
      when taste aversions are significantly weaker if testing occurs 1 day after
      conditioning compared to tests conducted 3 or more days after conditioning. Since
      all previous demonstrations of this phenomenon have occurred following
      conditioning with the drug lithium chloride (LiCl), it was necessary to determine
      if the increased drinking at the 1-day interval was due to the aftereffects of
      LiCl. The present experiment explored the presence of retention interval
      differences following the use of a nonpharmacological unconditioned stimulus
      (US), rotational stimulation. Following a saccharin-rotation pairing, a saccharin
      aversion was seen at a 5-day testing interval, and this aversion was
      significantly stronger than the aversion observed at a 1-day test. Thus, these
      results are clear in showing that the retention interval effect occurs following
      conditioning with a nonpharmacological US, and this outcome allows for the
      refutation of an aftereffects of LiCl hypothesis.

PMID- 8559798
TI  - Age-related changes in learning, memory, and lipofuscin as a function of the
      percentage of SAMP8 genes.
AB  - SAMP8 (P8) mice are characterized by impaired learning and memory relatively
      early in their life, while CD-1 mice show impairment later in life. A series of
      paternal backcross strains were developed from a CD-1 dame and P8 sire. Siblings
      from each backcross were bred to establish strains with 50% to 97% P8 genes. F4
      mice, 4 or 12 mo of age, were trained to avoid foot shock in a T-maze with
      retention tested 1 wk later. After testing, brain sections were examined for
      lipofuscin autofluorescence. At 4 mo of age, all strains, including the CD-1 and
      P8 strains, showed no significant differences in learning, retention or
      lipofuscin deposits. At 12 mo of age, groups with 94%, 97% P8 genes or P8 mice
      (100%) required significantly more trials to learn the task or relearn the task 1
      wk later than groups with 88% or fewer P8 genes. Lipofuscin deposits increased in
      the hippocampus as the percentage of P8 genes increased suggesting that many
      genes control aging of the brain. However, the sudden appearance of impaired
      learning in the 94% strain suggests that the mechanism(s) responsible for the
      impairment involves a few recessive genes and are independent of the mechanisms
      controlling the general aging of the brain.

PMID- 8559799
TI  - Characterization of the replicon from the lactococcal theta-replicating plasmid
      pJW563.
AB  - The replication region of the lactococcal plasmid pJW563 was localized to a 2.3
      kb EcoRI fragment. This DNA fragment was sequenced ans a 1155-bp open reading
      frame, repB563, encoding a putative protein RepB563 of 385 amino acids was found.
      An AT-rich noncoding region, repA563, was found upstream of repB563. This segment
      included several direct and inverted repeats. A downstream 591-bp open reading
      frame, ORF X, which was not necessary for replication, was putatively
      translationally coupled to repB563, RepB563 supplied in trans could support
      replication of a plasmid containing repA563 and a truncated repB563. This
      observation suggests that RepB563 is a trans-acting replication protein, and
      repA563 the cis-acting origin of replication, repA563, repB563, and the beginning
      of ORF X showed high homology to similar regions in a family of lactococcal theta
      replicating plasmids. The repA DNA sequences and the RepB amino acid sequences of
      the plasmids were aligned and the consensus sequences generated. The comparison
      revealed highly conserved areas among this family of plasmids. In addition,
      variable domains emerged, presumably having a plasmid specific function, pVS40
      and pC1305 were plasmids with replication proteins showing high homology to
      RepB563. Despite this homology, replication from repA563 could not be supported
      by the pVS40 or pC1305 replication protein supplied in trans. Likewise the pJW563
      protein could not support replication from the pVS40 origin. pJW563 was found to
      be compatible with the pVS40 and pC1305 replicons. The results indicate that
      pJW563 belongs to the widespread family of lactococcal theta-replicating
      pladmids. Despite the high homology between their replicons, the interaction
      between the replication origin and the protein is highly specific in many cases
      rendering the plasmids compatible.

PMID- 8559800
TI  - The Corynebacterium xerosis composite transposon Tn5432 consists of two identical
      insertion sequences, designated IS1249, flanking the erythromycin resistance gene
      ermCX.
AB  - Analysis of the 50-kb R-plasmid pTP10 from the clinical isolate Corynebacterium
      xerosis M82B revealed that the erythromycin resistance gene, ermCX, is located on
      a 4524-bp composite transposable element, Tn5432. The ends of Tn5432 are
      identical, direct repeats of an insertion sequence, designated IS1249, encoding a
      putative transposase of the IS256 family. IS1249 consists of 1385 bp with 45/42
      imperfect terminal inverted repeats. The nucleotide sequence of the 1754-bp
      Tn5432 central region is 99% identical to the previously sequenced erythromycin
      resistance region of the Corynebacterium diphtheriae plasmid pNG2. It encodes the
      erythromycin resistance gene, ermCX, and an ORF homologous to the amino-terminal
      end of the transposase of IS31831 from Corynebacterium glutamicum. Transposons
      with regions flanking the insertion sites were recovered from the C. glutamicum
      chromosome by a plasmid rescue technique. Insertion of Tn5432 created 8-bp target
      site duplications. A Tn5432-induced isoleucine/valine-auxotrophic mutant was
      found to carry the transposon in the 5' region of the ilvBNC cluster; in pTP10
      the transposon is inserted in a region similar to replication and partitioning
      functions of the Enterococcus faecalis plasmid pAD1 and the Agrobacterium
      tumefaciens plasmid pTAR.

PMID- 8559801
TI  - Genetic analysis of the minimal replicon of plasmid pIP417 and comparison with
      the other encoding 5-nitroimidazole resistance plasmids from Bacteroides spp.
AB  - The nucleotide sequence of the DNA replication origin region of a Bacteroides
      vulgatus plasmid, pIP417, encoding 5-nitroimidazole resistance has been
      determined. This region of 1934 bp presents some characteristics similar to those
      of other replication protein-dependent origins. It contains a large open reading
      frame which could encode a basic Rep protein (RepA) of 36.8 kDa. Upstream of this
      ORF exist an AT-rich region, three direct repeats (iterons) of 21 bp, multiple
      DnaA binding sites, and sites, and sites for the integration host factor (IHF).
      Moreover, the amino acid sequence of the pIP417 RepA protein shows similarities
      with those of other Rep proteins encoded by plasmids of gram-negative bacteria:
      pRO1600 from Pseudomonas aeruginosa; pPS10 from Pseudomonas syringae; pFA3 from
      Neisseria gonorrhoeae; and two cryptic plasmids from Campylobacter
      hyointestinalis and Butyrivibrio fibrisolvens. Although RepA can be expressed in
      an Escherichia coli in vitro transcription-translation assay, vectors containing
      the pIP417 replication origin did not replicate in E. coli. The homology of the
      pIP417 replication region with the corresponding regions of other Bacteroides
      spp, plasmids was also studied by Southern blot hybridization. The results
      indicated that the repA gene of plasmid pIP417 is homologous to that of plasmid
      pIP421, but not of plasmid pIP419. The replication region of plasmid pIP421 was
      sequenced and showed about 80% identity at the nucleotide level with that of
      pIP417. A small (3634-bp) cloning vector (pFK12) of entirely defined nucleotide
      sequence was constructed for Bacteroides spp.

PMID- 8559802
TI  - Construction of a cloning vector from a naturally occurring plasmid of Salmonella
      typhimurium.
AB  - A naturally occurring plasmid isolated from a drug-resistant strain of Salmonella
      typhimurium (993) has been used to construct a plasmid vector for cloning in a
      wild strain of Salmonella. The strain (993) contains at least two plasmids. The
      smaller plasmid (9 kb) contains an ampicillin-resistant marker, while the larger
      one (25 kb) is cryptic. Physical mapping of the 9-kb plasmid and construction of
      a 3.5-kb derivative have been carried out. This plasmid has been used for cloning
      in a restriction+modification+strain of S. typhimurium using a conventional
      calcium chloride method. It exhibited better efficiency of transformation than
      other commonly used plasmids such as pBR322 or its derivatives and transformants
      were found to be stable in the absence of antibiotic selection. The vector is
      compatible with pBR322 and can be used to study the expression of cloned genes in
      minicells.

PMID- 8559803
TI  - pDcsA vectors for strictly regulated protein synthesis during early development
      of Dictyostelium discoideum.
AB  - Two expression vectors have been constructed to express proteins exclusively in
      developing cells of Dictyostellium discoideum. In these Escherichia coli/D.
      discoideum shuttle vectors, proteins are synthesized under control of the
      promoter of the contact site A (csA) gene, which is efficiently suppressed during
      growth and becomes strongly activated during early development of D. discoideum.
      The pDcsA vectors appear to be valuable tools for the production of proteins that
      are not compatible with growth of D. discoideum cells.

PMID- 8559804
TI  - Frequency of aggregation substance and cytolysin genes among enterococcal
      endocarditis isolates.
AB  - Enterococcus faecalis blood isolates were probed for the serine protease
      activator of cytolysin (cylA) and aggregation substance (asa1), traits that
      generally reside on pheromone-responsive plasmids, to determine how commonly
      these genotypes were associated with disease. In dot blot assays, no significant
      difference was found in the frequency of asa1 for blood isolates [55 of 103
      (54%)] and isolates recovered from stool [9 of 14 (60%); P > 0.1, chi 2 test]. In
      contrast, cylA occurred more frequently among bacteremia isolates [34 of 68
      (50%)] than endocarditis [4 of 35 (11%)] or stool isolates (0 of 14; P < 0.001;
      chi 2 test). However, when the clonality of isolates was accounted for, the
      frequency of asa1 and cylA among unrelated strains was not significantly
      different among the three sets of strains (P > 0.2, chi 2 test). The lack of
      enrichment for asa1 or cylA among clonally unrelated E. faecalis bloodstream
      isolates fails to support a role for plasmid-encoded aggregation substance or
      cytolysin in the transition from bacteremia to endocarditis. Clonally related,
      cytolytic strains, however, demonstrated an increased propensity to cause
      bloodstream infection.

PMID- 8559805
TI  - Sequence analysis of an Erwinia stewartii plasmid, pSW100.
AB  - The nucleotide sequence of the smallest plasmid of Erwinia stewartii SW2 was
      determined. This plasmid, pSW100 (4272 bp), consists of a 702-bp region
      homologous to the origins of replication of plasmids p15A, ColE1, and ColA.
      Plasmid pSW100 also contains sequences homologous to the bom region and mobCABD
      genes of ColE1, except that a single-base deletion in mobA has been detected.
      This deletion did not affect the mobilization ability of pSW100 by an endogenous
      conjugative plasmid of E. stewartii SW2, pDC250. Plasmid pSW100 also has a 1596
      bp open reading frame with five 132-bp perfect repeats. However, this open
      reading frame and the repeats are not required for plasmid replication.
      Furthermore, curing of pSW100 did not cause any phenotypic change, suggesting
      that this plasmid is not essential for the survival of the organism.

PMID- 8559806
TI  - Development of a heterodimer plasmid system for the introduction of heterologous
      genes into streptococci.
AB  - We have previously constructed a model secretion system for oral streptococci
      using the secretory domain of the Streptococcus mutans GS-5 gtfB gene. As an
      initial step in developing systems for secreting protein fusions containing a
      glucan-binding polypeptide from streptococci, a DNA fragment corresponding to the
      glucan-binding domain (GBD) of the glucosyltransferase-S enzyme from strain GS-5
      was fused to the gtfB secretory domain. However, it was not possible to clone the
      hybrid gene into Escherichia coli-streptococcal shuttle plasmids using E. coli as
      host cells. Integration of the hybrid GBD gene into the Streptococcus gordonii
      chromosome was directly accomplished utilizing a strategy involving a novel
      heterodimeric plasmid system. The heterodimer was constructed by ligating
      together two plasmids each containing DNA fragments homologous with a
      corresponding region of the S. gordonii chromosome flanking the hybrid GBD gene
      following a double crossover recombination event. However, this single-copy
      integrant secreted limited quantities of the GBD protein. In order to achieve
      high-level expression of the protein, the hybrid GBD gene was integrated into
      resident plasmids in S. gordonii following construction of intermediate
      heterodimeric plasmids. These plasmids contained the GBD gene flanked by
      sequences homologous to regions of the resident plasmids. The presence of the GBD
      protein in culture fluids from transformants harboring the multicopy plasmids
      demonstrated the secretion of the functional GBD protein. The strategy
      successfully developed for secreting the GBD in the streptococci should be
      adaptable for other organisms for which gene transfer systems are available. In
      addition, these systems will allow the direct introduction of genetic constructs
      when the constructs cannot be stably maintained in shuttle vectors within
      intermediate hosts such as E. coli.

PMID- 8559807
TI  - Transformation of the methylotrophic actinomycete Amycolatopis methanolica with
      plasmid DNA: stimulatory effect of a pMEA300-encoded gene.
AB  - Amycolatopsis methanolica contains a 13.29-kb plasmid (pMEA300) present both in
      the free state and integrated at a unique genomic location. A pMEA300-free
      derivative (strain WV1) was selected, allowing further analysis of pMEA300
      encoded functions. Whole cells of strain WV1 could be transformed at high
      frequencies (approximately 10(6) transformants per microgram of plasmid DNA) with
      both circular and linear plasmid DNA, provided that the pMEA300-encoded stf
      (stimulation of transformation frequency) gene was present. stf would encode a
      putative protein of 373 amino acids with M(r) 40,201, resembling putative
      regulatory proteins involved in sporulation of Streptomyces griseus and
      Streptomyces coelicolor.

PMID- 8559808
TI  - Breast enlargement and reduction: results from a breast cancer case-control
      study.
AB  - In a population-based case-control study of breast cancer that included 2174
      cases and 2009 population controls under 55 years of age, prior breast implants
      were reported by 36 cases versus 44 controls. After adjustment for the matching
      factors as well as variables associated with both breast cancer risk and breast
      enlargement (race, family history of breast cancer, body size, screening
      history), the relative risk of breast cancer associated with a prior implant was
      0.6 (95% CI 0.4-1.0). The reduced risk persisted with increasing interval since
      surgery, arguing against selection bias as an explanation. Further, although a
      deficit of in situ tumors was seen among women with implants (RR = 0.2), the risk
      associated with implants remained reduced for both localized and distant tumors
      (RR = 0.8 for both stages). In a smaller group of women who had prior breast
      reduction surgery (10 cases, 13 controls), a reduced risk of breast cancer also
      was observed (RR = 0.7, 95% CI 0.3-1.6). The results of this study must be
      interpreted cautiously because of the small number of women involved and reliance
      on patient reports of prior operations. In not showing any elevation in breast
      cancer risk following a breast implant, our results confirm several record
      linkage studies but contradict some clinical studies that suggest an adverse
      effect. Additional investigations are needed in relation to specific types of
      breast implants, including the polyurethane-coated implants, which have been
      linked to high cancer rates in laboratory animals.

PMID- 8559809
TI  - Long-term studies of metopic synostosis: frequency of cognitive impairment and
      behavioral disturbances.
AB  - Although the occurrence of cognitive impairment and behavioral disturbances in
      patients with metopic synostosis has been described, the incidence of this
      dysfunction has not been established. The records of 36 consecutive children with
      metopic synostosis followed at one craniofacial center from 1978 to 1993 were
      reviewed and parental questionnaires were completed to establish the frequency of
      mental retardation, learning disabilities, and behavioral problems associated
      with this synostosis. Documentation of syndromes, abnormal karyotype, and central
      nervous system anomalies also was done. The study group consisted of 27 males and
      9 females. The average age at most recent follow-up was 7 years and 1 month
      (range 6 months to 22 years). Two patients had chromosomal abnormalities (9p
      syndrome and trisomy 21). On the basis of CT and MRI scans, intracranial
      anomalies were identified for only one patient having an absent corpus callosum.
      Thirty-two of the study patients had adequate information for longitudinal
      assessment. Twenty patients have normal development without apparent disability.
      Of these, those of school age are at appropriate grade level. Eight patients have
      mild to moderate learning disabilities or behavioral problems, including
      attention deficit/hyperactivity disorder and impaired language development. Four
      patients have significant mental impairment. Impaired cognitive development was
      not limited to children with abnormal karyotype or central nervous system
      anomaly. Cognitive and behavioral abnormalities occur in at least a third of
      patients with metopic synostosis. The, at times, subtle nature of these
      abnormalities mandates longitudinal developmental and neurologic evaluation for
      infants with metopic synostosis.

PMID- 8559810
TI  - Plagiocephaly: differential diagnosis based on endocranial morphology.
AB  - Plagiocephaly is a descriptive term that connotes an asymmetrically oblique or
      twisted head. Such cranial dysmorphology has a number of etiologies, the most
      common of which are unicoronal synostosis, unilambdoid synostosis, and
      plagiocephaly without synostosis. Use of the term plagiocephaly in the literature
      is often ambiguous in that at times it is used inclusively for all etiologies
      while at other times it is used exclusively as a synonym for unicoronal
      synostosis. Although differentiation by physical examination among unicoronal
      synostosis, unilambdoid synostosis, and plagiocephaly without synostosis usually
      is possible for an experienced observer, inexperienced observers often have
      difficulty making an anatomically accurate diagnosis even with the assistance of
      conventional skull radiographs. High-resolution CT scans, including three
      dimensional osseous surface re-formations, have become a standard element in the
      evaluation of craniofacial anomalies in many centers. We hypothesized that the
      three major etiologies of plagiocephaly could be unambiguously differentiated by
      means of endocranial three-dimensional CT osseous surface re-formations. Archival
      pretreatment CT data on 15 unicoronal synostosis, 4 unilambdoid synostosis, and
      15 plagiocephaly without synostosis patients were reviewed to define,
      qualitatively and quantitatively, the characteristics of the endocranial base
      morphologies for each group; in addition to visual dysmorphology specific to each
      group, there was a statistically significant difference in the angle of deviation
      from the midlines of the anterior and posterior cranial fossae among unicoronal
      synostosis, unilambdoid synostosis, and plagiocephaly without synostosis. Four
      radiologists experienced in reading images of craniofacial anomalies were
      oriented to the group characteristics and then instructed to perform differential
      diagnosis for each of the 34 patients using only the endocranial three
      dimensional CT images. The raters were blind to all other clinical and diagnostic
      information. The raters correctly diagnosed unicoronal synostosis. Errors were
      made in differentiation of unilambdoid synostosis and plagiocephaly without
      synostosis. These errors resulted from the raters' reliance on image inspection
      rather than quantitation of anteroposterior fossae midline angulation. Such
      quantitation unambiguously differentiated between unilambdoid synostosis and
      plagiocephaly without synostosis in the "error" cases. The endocranial base
      dysmorphology of patients with plagiocephaly is etiology-specific for unicoronal
      synostosis, unilambdoid synostosis, and plagiocephaly without synostosis. Three
      dimensional CT endocranial base images can assist differential diagnosis of
      plagiocephaly.

PMID- 8559811
TI  - Morbidity associated with increased intracranial pressure in Apert and Pfeiffer
      syndromes: the need for long-term evaluation.
AB  - Although the incidence of elevated intracranial pressure is increased in patients
      with the craniosynostosis syndromes, the significance of these findings and their
      impact on clinical practice remain unclear. The morbidity related to elevated
      intracranial pressure in patients with Apert and Pfeiffer syndromes was reviewed.
      Sixty-seven patients with Apert syndrome and 39 patients with Pfeiffer syndrome
      were identified. The morbidity in 5 of the 106 patients (4.7 percent) was felt to
      be directly related to persistently elevated intracranial pressure. These
      included 2 deaths, 1 due to brainstem herniation after an elective subcranial Le
      Fort III advancement and 1 following removal of a lumboperitoneal shunt during
      the surgical release of syndactyly. The remaining 3 complications included
      bilateral papilledema detected 3.5 years after cranial vault remodeling in 1
      patient and venous hypertension with excessive bleeding detected during elevation
      of the bicoronal flap in 2 patients, resulting in delay of a planned Le Fort III
      advancement. Patients with the syndromal craniosynostoses are at risk for
      complications resulting from elevated intracranial pressure from infancy through
      adulthood despite surgical attempts to increase cranial capacity in infancy.
      Clinical guidelines are proposed by which these patients should be evaluated
      beyond infancy in a regular fashion so as to reduce morbidity from unrecognized
      elevations in intracranial pressure.

PMID- 8559812
TI  - The sandwich epicranial flaps.
AB  - Sandwich epicranial flaps are prefabricated composite flaps that have multiple
      uses in reconstructing the middle and the lower facial region. Sandwich
      epicranial flaps always comprise the galea and a full-thickness skin graft; they
      may, in addition, include the temporal muscle and a fragment of parietal bone.
      According to their composition, four types of sandwich epicranial flaps are
      described. Experience with a use of 36 sandwich epicranial flaps (13 with
      vascularized bone) is reported. A few examples demonstrate the use of sandwich
      epicranial flaps in dramatic facial mutilation following noma in children. The
      sandwich epicranial flap can be performed at any age, does not require
      microsurgical anastomoses, and has a low complication rate. It is particularly
      useful for major reconstructive procedures in children.

PMID- 8559813
TI  - Median cleft of the lower lip and mandible: case reports, a new embryologic
      hypothesis, and subdivision.
AB  - Median clefts of the lower lip and mandible are rare. In the literature so far,
      about 62 cases have been described. In addition, three more patients are
      presented here. These cases show a broad variation in the severity of this
      deformity, ranging from a simple notch in the vermillion to a complete cleft of
      the lip involving the tongue, the chin, the mandible, the supporting structures
      of the median of the neck, and the manubrium sterni. Several hypotheses
      concerning the pathogenesis of median clefts of the lip and mandible have been
      proposed. Most authors consider it to be a failure of fusion of the first pair of
      branchial arches or failure of mesodermal penetration into the midline. From our
      embryologic point of view, however, instead of paired branchial arches, only one
      first branchial arch develops during the early embryonic period (< or = 17 mm
      crown-rump length). Within this first branchial arch, two mandibular processes
      grow out, separated by a groove in the median. These mandibular processes do not
      fuse but merge during the late embryonic period (> or = 17 mm to < or = 60 mm
      crown-rump length). In the same developmental period, there is formation of the
      lip and the alveolar process and the anlage and outgrowth of one membrane bone
      center in each mandibular process, resulting in the formation of the mandible
      with its symphysis. As a consequence of the preceding, we propose the following
      subdivision of the median clefts of the lip and/or mandible: Hypoplasia of the
      mandibular processes during the early embryonic period will lead to the severest
      cleft of the mandible extending into the neck. During the late embryonic period,
      the less severe median clefts will develop. Disturbances of the outgrowth of bone
      centers of the mandible, resulting in nonformation of its symphysis, cause
      clefting of the mandible with involvement of all related soft tissues. Defects in
      the merging process produce just a notch of the vermilion or a higher cleft of
      the lower lip with or without involvement of the alveolar process of the
      mandible. In conclusion, the variety of the clefts in the median of the lower lip
      and/or mandible as well as the low rate of incidence can be explained by the
      embryologic hypothesis proposed here.

PMID- 8559814
TI  - Open rhinoplasty without transcolumellar incision.
AB  - Traditional open rhinoplasty produces a scar on the columella. To avoid such a
      scar and still obtain a wide exposure of the nasal framework, the bilateral
      paramarginal incisions close to the columella were extended into the nasal
      floors, and a wide undermining of the base of the columella was performed. The
      nasal tip with the crura together could then be presented through one of the
      nostrils. Conditions similar to those of the traditional open rhinoplasty wer
      thus achieved. The technique has been used in selected patients for 8 years with
      satisfactory results. In conclusion, the open rhinoplasty without transcolumellar
      incision can replace the traditional transcolumellar open rhinoplasty technique.

PMID- 8559815
TI  - Optimizing bone-graft nasal reconstruction: a study of nasal bone shape and
      thickness.
AB  - Nasal reconstruction may best be carried out with bone grafting in certain cases
      of loss of structural support. In order to optimize both the aesthetic and
      functional results of bone-graft nasal reconstruction, we studied the shape and
      thickness of the normal human nasal bone. Sixty Caucasian skull nasal bones were
      measured by width throughout their length at three planes of depth. Seventeen
      Caucasian cadaver nasal bones were examined to determine the thickness of the
      bone throughout its length at three sagittal planes. The results showed that the
      nasal bone was widest at the nasofrontal suture (14 mm), narrowest at the
      nasofrontal angle (10 mm), and then widened again to a maximum width of 12 mm
      about 9 to 12 mm inferior to the nasofrontal angle. The nasal bone was thickest
      superiorly at the nasofrontal angle (average 6 mm) and progressively thinned
      toward the tip. It was 3 to 4 mm thick in the critical area where screws are most
      commonly placed for fixation (5 to 10 mm inferior to the nasofrontal angle). From
      these data, three-dimensional models of the normal nasal bone shape were
      formulated and used in clinical bone-graft cases.

PMID- 8559816
TI  - Simplified procedure for aesthetic improvement of facial contour by maxillary
      augmentation using a porous hydroxyapatite graft for maxillofacial deformity.
AB  - A simplified procedure of maxillary augmentation with a porous hydroxyapatite
      block graft in the anterior aspect of the maxillary parapiriformis area is
      described. This procedure is an alternative for maxillary advancement osteotomy
      and is simple to perform for maxillofacial deformity of cleft lip and palate and
      other deformities. It is effective for facial aesthetics in association with
      mandibular surgery, such as mandibular setback by sagittal splitting osteotomy,
      mandibular segmental osteotomy with premolar extraction, bimaxillary osteotomy,
      and/or genioplasty. We used this procedure on 21 patients (15 for cleft lip and
      palate jaw deformity and 6 for aesthetic reasons). Although postoperative
      infection requiring removal of the hydroxyapatite block occurred in one cleft
      deformity patient, satisfactory results were obtained in all patients.

PMID- 8559817
TI  - The role of microfixation in malar fractures: a quantitative biophysical study.
AB  - Microfixation and wire fixation techniques were used in combination with
      miniplates in the stabilization of simulated simple zygoma fractures in four
      fresh human cadaver heads. An orthogonal conveyer and rigid steel test frame were
      used to test rotational stability after deforming forces were applied. After
      testing multiple combinations at an initial deforming force of 5 kg, selected
      combinations were tested over a range of 2 to 22 kg. Evaluation of force
      displacement data revealed that three-point fixation with miniplates was superior
      to all other methods, in agreement with previous studies. The combination of
      lateral buttress miniplate fixation in conjunction with microfixation at the
      zygomaticofrontal and infraorbital rim regions exhibited stable characteristics
      over the range of forces applied. Miniplate-microplate combinations exhibited
      greater stability than corresponding miniplate-wire combinations. The combination
      of miniplate-microplate fixation clinically allows a balance between stability
      and aesthetics in selected zygoma fractures.

PMID- 8559818
TI  - Microsurgical correction of facial asymmetry in 60 consecutive cases.
AB  - Restoring soft-tissue contour in patients with facial asymmetry is a difficult
      problem for plastic surgeons. We report our experience with 57 consecutive
      patients who underwent 60 microvascular free flaps for the correction of facial
      asymmetry between July of 1989 and June of 1994. Etiologies of facial asymmetry
      included hemifacial microsomia, hemifacial atrophy, postradiation sequelae, burns
      and trauma, and selected congenital anomalies. Thirty-eight patients were
      reconstructed with a customized parascapular flap incorporating extensions of
      dorsal thoracic fascia. Other donor sites utilized were as follows: six
      superficial inferior epigastric flaps, three myocutaneous flaps, seven muscle
      flaps, and six fasciocutaneous flaps with bone. To correct facial asymmetry, the
      recipient site was dissected through a limited preauricular incision whenever
      feasible, and the superficial temporal artery and vein were used as recipient
      vessels. A monitoring skin paddle was rarely used. There were no flap losses in
      this series. Six patients experienced a postoperative hematoma, three of which
      were drained at the bedside. Limited skin slough occurred in three patients. No
      donor-site complications other than hypertrophic scarring were encountered. Flap
      revisions were performed in 22 of the 57 patients to maximize aesthetic results.
      Based on our experience, we feel that the operative approach presented here
      allows excellent and stable correction of facial asymmetry due to a variety of
      etiologies. Furthermore, this technique is applicable to other congenital
      craniofacial deformities such as Treacher-Collins syndrome and orbital-facial
      clefts.

PMID- 8559819
TI  - Comparison of resource costs between implant-based and TRAM flap breast
      reconstruction.
AB  - Resource costs, as measured by hours of time in the operating room, days of stay
      in the hospital, and other costs of care, were evaluated for 240 patients who
      underwent mastectomy with immediate breast reconstruction using either TRAM flaps
      or breast implants at The University of Texas M. D. Anderson Cancer Center. To
      make costs comparable, only patients who completed reconstruction of the nipple
      were included. As expected, the initial resource costs of implant-based
      reconstruction were much lower than those of TRAM flap reconstruction. After
      correcting for patients whose reconstructions were unsuccessful and including the
      costs of surgery subsequent to the initial reconstruction, however, the cost
      advantage of implant-based reconstruction disappeared. If current trends
      continue, it is likely that with increased follow-up, the long-term resource
      costs of implant-based reconstructions will continue to increase, while those of
      autogenous tissue reconstructions will not. Autogenous breast reconstruction with
      the TRAM flap therefore appears to be more cost-effective, in terms of time as
      well as dollars, in the long run than reconstruction based on prosthetic
      implants.

PMID- 8559820
TI  - A 30-year experience with vertical mammaplasty.
AB  - In 1964, I started using vertical mammaplasty without a submammary scar for all
      breast reductions. This technique was based on the following principles: a
      central wedge resection, an upper pedicle for the areola, no undermining, and a
      vertical scar to finish off. Because of the drawings, there was a pitfall: In
      large breasts, the inferior portion of the vertical scar was showing below the
      submammary fold. This is why, in 1977, I modified the technique with the addition
      of a short horizontal scar to eliminate this drawback. At the time, I was
      respecting the dogma that the length of a vertical scar should not exceed 5.5 cm.
      Taking a look again at my patients after a few months, I was surprised to find
      that the horizontal scar had moved upward. This led me to verify that the
      distance between the inferior border of the areola and the inframammary fold was
      variable with the size of the breast. I was then convinced that it was possible
      to finish every mammaplasty with a vertical scar. Thus I modified the procedure
      again to make the vertical scar stay above the inframammary fold in almost all
      patients. In a personal series of 710 patients (1350 breasts) operated on from
      1964 to 1994, mastopexy was performed in 439 breasts and breast reduction was
      performed in 911 breasts. There were few complications. This long experience with
      vertical mammaplasty indicates that it is a safe procedure giving long-lasting
      results.

PMID- 8559821
TI  - Nipple-areolar perfusion and reduction mammaplasty: correlation of laser Doppler
      readings with surgical complications.
AB  - Clinical assessment of nipple-areolar perfusion by color, capillary refill, and
      temperature during and after reduction mammaplasty is generally satisfactory.
      However, the estimation of vascular perfusion in patients with very large breasts
      or dark-skinned women is difficult. If marginal perfusion of the nipple-areolar
      areas is undetected, necrosis is likely. To this point, no studies have tested
      the ability of the laser Doppler perfusion monitor to give absolute alarm values
      that would suggest marginal perfusion in the nipple-areola following reduction
      mammaplasty. We therefore completed a prospective study of areolar perfusion
      during surgery and for up to 24 hours following reduction mammaplasty. Fifty-four
      patients were studied and data collected from 104 breasts. Laser Doppler
      perfusion was measured with a LASERFLO BPM2 Blood Perfusion Monitor (Vasamedics,
      St. Paul, Minn.). Perfusion values were recorded for each breast following
      anesthesia but prior to the incisions, at the end of surgery, and every 2 hours
      for 24 hours. Patients were divided into three groups according to their follow
      up results: no complications (92 breasts), minor complications (9 breasts), and
      patients with tissue necrosis (3 breasts). The no complications group had a
      perfusion of 4.8 ml/min/100 gm following the reduction procedure, while the minor
      complications and tissue necrosis groups had average perfusions of 1.4 and 0.8,
      respectively, immediately after incision closure. The average tissue removed from
      each group was 811, 1171, and 2118 gm for the no complications, minor
      complications, and tissue necrosis groups, respectively. The results from this
      study suggest that a laser Doppler perfusion monitor could prove useful for
      monitoring areolar perfusion following reduction mammaplasty, especially in
      patients with extremely large breasts and/or dark skin. Our studies have shown
      that laser Doppler perfusion values that consistently are in the range of 1.0 to
      2.0 ml/min/100 gm indicate marginal perfusion, and the recovery of these patients
      should be followed closely. Furthermore, patients with consistent perfusion
      values equal to or less than 1.0 coupled with other clinical signs of low
      perfusion should be considered for suture removal and/or free nipple graft.

PMID- 8559822
TI  - Computed tomographic observations on subcutaneous fat: implications for
      liposuction.
AB  - The anatomy of the abdominal subcutaneous tissues is discussed in the light of
      data obtained in 20 female patients examined on a modern computed tomographic
      system. We have shown that the superficial fascia, which separates the
      superficial and deep layers of subcutaneous fat, forms a continuous
      circumferential fascial plane. This superficial fascia, contrary to previous
      reports, does not appear to merge with the deep fascial plane around the external
      oblique muscle. The fat in the deep subcutaneous layer, bounded by the
      superficial fascia, is the target for liposuction techniques. The CT data have
      shown that about 50 percent of subcutaneous fat resides within this deep layer.

PMID- 8559823
TI  - Ultrastructural observations of lymphatic vessels in lymphedema in human
      extremities.
AB  - Microsurgical lymphaticovenous anastomoses were done on a total of 14 patients.
      Six upper extremities of six female patients (average age 56.5 years) were
      operated on with lymphaticovenous anastomoses and were followed up for 17 months
      or more after surgery (average 25.5 months). Twelve legs of eight patients
      (average age 44.6 years) also were operated on and followed up for 12 months or
      more after surgery (average 23.4 months). Among these patients, 33 biopsied
      lymphatic trunks with lymphedema in 16 extremities of 12 patients were evaluated
      histologically by light and electron microscopy. Regarding the operative effect
      in the arms, the decreased circumference of the arms ranged from 2 to 9 cm
      (average 5.3 cm). The rate of preoperative versus postoperative excess
      circumference decreased in range from 25 to 94.7 percent (average 65.7 percent).
      As for the surgical effect in the legs, half the legs showed improvement. These
      postoperative improvements showed no correlation with the preoperative duration
      of edema and excess circumference in either the upper or lower extremities.
      Histologically, in the initial stage of lymphedema, there was destruction of both
      endothelial cells and smooth muscle cells in the proximal level of the lymphatic
      trunks. The lumen of some proximal trunks was then occluded by organization with
      a few small recanalizations, but the distal lymphatics remained patent with
      minimal destruction of both the endothelial cells and the smooth muscle cells
      even in the later stage of lymphedema. These results suggest that the occlusions
      of the lymphatic trunks and degeneration of the smooth muscle cells may start
      from the proximal ends of the extremities and that the timing of the occlusions
      and the degeneration of smooth muscle cells may not correspond to the duration of
      edema. It is also considered that because of the smooth muscle degeneration, the
      lymph-drainage capacity of the lymphatic trunks may be remarkably weakened in the
      proximal lymphatics of the extremities. Therefore, it is suggested that the
      remaining lymphatic drainage function with the smooth muscle cells may correlate
      with the postoperative improvement of edema. It is also suggested that the
      preoperative ultrastructural examination of the lymph-drainage capacity may be a
      suitable method for predicting the surgical effect and operative indication for
      lymphatic edema in the extremities.

PMID- 8559824
TI  - A radiographic perfusion study of the cephalic venous flap.
AB  - The circulatory anatomy of the arterialized cephalic venous flap was investigated
      radiographically in five fresh cadavers. Microfil, which was dripped from the
      caudal end of the cephalic vein, flowed first into the concomitant veins and then
      into an intimate vascular network around the cephalic vein. The Microfil then
      flowed to a septocutaneous perforator of the radial artery through the vascular
      network around the cephalic vein. This suggests that in the arterialized cephalic
      venous flap there is a circulatory pathway by means of the cephalic vein to the
      venous network around the cephalic vein, to the arterial network around the
      cephalic vein, to the arterial system, and to the venous system returning to the
      cephalic vein.

PMID- 8559825
TI  - Urethral reconstruction using the radial artery forearm free flap: conventional
      and prefabricated.
AB  - For successful reconstruction of the scarred urethra it is logical to employ well
      vascularized skin flaps. The radial artery forearm free flap is ideal for this
      purpose. This paper describes the first seven consecutive patients in whom we
      have used this flap for urethral reconstruction. In one, the forearm skin was too
      hirsute for urethral lining, and a prefabricated hairless skin flap was created
      by application of a preliminary full-thickness skin graft from a nonhairy site
      onto the forearm fascia. The longest follow-up is 5 1/2 years.

PMID- 8559827
TI  - What's in a name? Everything and nothing.

PMID- 8559826
TI  - Superficial ulnar artery flap.
AB  - Superficial ulnar artery is a known abnormality. It replaces the normal ulnar
      artery and has a superficial course. Its accidental division during the raising
      of the radial forearm flap can seriously jeopardize hand circulation. The
      presence of this vessel can be diagnosed preoperatively by careful palpation, and
      its course can be confirmed by vascular Doppler. This abnormality was found in
      9.38 percent of upper limbs in cadaver dissections. A similar incidence of 9.12
      percent was observed in clinical practice. Superficial ulnar artery gives several
      good-sized fasciocutaneous branches in the forearm. A type C fasciocutaneous
      flap, similar to a radial forearm flap, can be raised with safety on this
      anomalous vessel. Over the past 4 years, six such flaps have been raised. The
      largest fap was 24 x 12 cm. The flaps can be made neurosensory. Palmaris longus
      muscle can be raised with the flap for bulk or as an active motor unit. The
      extralong pedicle with good-sized vessels makes free-flap transfer safe. The
      donor site heals uneventfully. The presence of this abnormality can be a trap to
      an unsuspecting surgeon but is in fact a boon if diagnosed in time.

PMID- 8559828
TI  - Congenital auricular deformity consisting of cleft concha and transposition of
      the earlobe and antitragus.
AB  - We have reported a patient with a congenital auricular deformity consisting of
      cleft concha transposition of the earlobe and antitragus. This is an extremely
      rare entity. We have named it congenital auricular deformity consisting of cleft
      concha and transposition of the earlobe and antitragus because the case we
      described is a congenital cleft auricle and transposition of the earlobe and
      antitragus in terms of position of the deformity.

PMID- 8559829
TI  - The retroangular flap for nasal reconstruction.
AB  - Many techniques can be used for nasal reconstruction. This paper describes the
      preliminary results of our study and shows a one-stage method for partial nasal
      reconstruction performed with a fasciocutaneous island flap with a retrograde
      blood supply based on the angular artery. This flap is called the retroangular
      flap. Six patients had been treated from January of 1993 to January of 1994. The
      technique is illustrated, and the correlated complications and results are also
      shown. The flap's color and texture have always been satisfactory. In one
      patient, the thickness of the flap required a secondary defatting. No sequelae
      were observed in the donor site.

PMID- 8559830
TI  - A custom-made nasal implant: prefabrication from curing of silicone adhesive.
AB  - When nasal augmentation is performed with implants fashioned from a piece of
      solid silicone block or commercially available prefabricated implants, the
      precise sculpturing of the ventral surface of the implant in order to conform to
      the convex contour of the nose is often difficult to achieve, increasing the
      possibility for malposition and extrusion. We devised two methods of making soft
      silicone elastomer implants from nasal cast models obtained from alginate
      impressions of patients' noses: type I, in which the implant is made from the
      curing of silicone adhesive that is spread on both sides of the sheet blueprint
      placed on the cast model, and type II, in which the implant is made only from the
      curing of silicone adhesive. Because these custom-made implants have a ventral
      surface of exact concave contour conforming to the convex surface of the nasal
      framework, they blend in nicely with the various configurations of the existing
      nasal framework and thus minimize malposition and extrusion. These implants also
      avoid having a prototype nose for everyone and are more cost-effective than
      commercially available implants.

PMID- 8559831
TI  - Refining silicone implant correction of pectus excavatum through computed
      tomography.
AB  - Silicone implant correction of pectus excavatum has yielded satisfactory results
      in asymptomatic patients. Problems have been encountered with accurate implant
      fabrication and fit due to the soft-tissue masking of actual sternal contours. We
      have employed computed tomography to reconstruct the pectus deformity to improve
      implant design and fit. Instability can be prevented with the reduced need for
      intraoperative manipulation as well.

PMID- 8559832
TI  - "Pull-through": a new technique for breast reduction in gynecomastia.
AB  - This paper reports a new technique for breast reduction in gynecomastia, removing
      the glandular parenchyma by pulling it through two incisions previously made for
      liposuction. These incisions are localized in the anterior axillary pilar area
      and on the right side of the inframammary fold. No complications have been
      reported in the 6-month follow-up visits of 11 patients. The technique makes it
      possible to eliminate the incision in the areolar area, avoiding its related
      complications. The advantage of this technique is that it removes the breast
      parenchyma without leaving any scars in the breast aesthetic unit, which, from a
      psychological point of view, has been greatly appreciated by our patients.

PMID- 8559833
TI  - The transversus and rectus abdominis musculoperitoneal (TRAMP) composite flap for
      vulvovaginal reconstruction.
AB  - The transversus and rectus abdominis musculoperitoneal (TRAMP) flap, a novel
      composite flap supplied by the deep inferior epigastric vessels, was used
      successfully for partial vulvovaginal reconstruction following anterior and
      posterior exenteration. The full potential of the TRAMP flap in vulvovaginal
      reconstruction is being investigated further.

PMID- 8559834
TI  - Reconstruction of the pharynx and overlying soft tissue by a partitioned free
      jejunal flap.
AB  - The partitioned free jejunal flap has proven useful in cases where soft-tissue
      coverage is required after pharyngeal reconstruction. It provides durable
      coverage and eliminates a second flap procedure.

PMID- 8559835
TI  - Color monitoring after replantation.
AB  - The recognition of postmicrosurgical minute skin color changes is an important
      element in assessing vascular insufficiency that has traditionally relied on a
      skilled microsurgeon's subjective clinical impression. This study investigates
      the use of a color monitor for the objective quantitative evaluation of such skin
      color changes. Twenty-two replanted digits were monitored postmicrosurgically
      with a color meter while deep skin temperature recordings, an established method
      of postmicrosurgical monitoring, were taken simultaneously. The results showed
      that the digits' clinical courses, namely, "uneventful," "necrosis,"
      "congestion," and "acute arterial obstruction," showed characteristic patterns of
      postmicrosurgical circulation that were reflected in skin color change
      measurements. The reliability of the color measurements was confirmed by the deep
      skin temperature recordings. This study suggests that skin color after
      microsurgery can be evaluated quantitatively with the proposed color monitoring
      system and that this system is useful for the diagnosis of postmicrosurgical
      vascular insufficiency.

PMID- 8559836
TI  - Growth factors in surgery.
AB  - Surgical reconstruction of functional and aesthetic defects is often compromised
      by donor-tissue limitations and wound-healing constraints--problems that can
      potentially be overcome by peptide growth factor therapy. The effectiveness of
      growth factor therapy in animal models and in limited human clinical trials has
      been realized. Epidermal growth factor (EGF), fibroblast growth factor (FGF),
      platelet-derived growth factor (PDGF), platelet-derived wound-healing formula
      (PDWHF), transforming growth factor (TGF), the bone morphogenetic proteins
      (BMPs), and general considerations of growth factor therapy are reviewed.

PMID- 8559837
TI  - The value of Polaroid photography in a burn unit.

PMID- 8559838
TI  - Nasal moulages.

PMID- 8559839
TI  - Do as the artists and sculptors do: the mastectomy specimen as a model to
      finalize TRAM flap shape in immediate breast reconstruction.

PMID- 8559840
TI  - Suborbicularis oculi fat pads.

PMID- 8559841
TI  - The unrecognized giants.

PMID- 8559843
TI  - The effect of lasers, electrocautery, and sharp dissection on cutaneous flaps.

PMID- 8559842
TI  - Macroscopic intraductal silicone gel.

PMID- 8559844
TI  - A new instrumentally tied approximation knot.

PMID- 8559845
TI  - The "supercharged" posterior calf fasciocutaneous flap.

PMID- 8559846
TI  - Necrosis of the nasal tip.

PMID- 8559847
TI  - Use of Gore-Tex.

PMID- 8559848
TI  - [Informing a child about his illness in HIV infection: words and meaning].
AB  - The account of the medical and psychological treatment of Pascal over a period of
      three years shows the complexity and the stakes of the problem that families and
      the medical core are faced with when confronted to a child infected by the HIV:
      to talk of his infection or his illness. How do you approach the problem with an
      8 year old child? What do you answer to his questions without the risk of
      triggering an unbearable death anxiety for him and his family? Starting with a
      lie, Pascal's mother will progressively realise the intrication of her own
      internal conflicts (that go back to her childhood) with her present suffering.
      She thus becomes able to look at her son's illness properly and discuss it with
      him in a healthy and natural manner. The question of whether to disclose his
      diagnosis to a child is discussed; some recommendations are suggested.

PMID- 8559849
TI  - [Anxiety and reconstructive surgery in children and adolescents].
AB  - Study of 133 children and adolescents hospitalized and operated in child and
      adolescent reconstructive surgery. We will study the fantasy representations of
      anxiety as it is expressed by this population, as well as the psychological
      repercussions of surgical interventions: behavior disorders, depression, anxiety.
      We will show that pre-adolescents and adolescents represent the most vulnerable
      patients in regard to the anxiety triggered by the surgical act and that some of
      them experience, at the time of the operation, episodes of psychic
      disorganization of psychotic appearance. We will look into the impact of this
      mutilating surgery and the weight of severe orthopedic handicaps, and have noted
      that the expression of anxiety isn't always in relation to the seriousness of the
      handicap and/or that of the intervention. The anxiety is linked to the
      psychological balance of the child which is largely due to the relationship he
      has with his parents and the feeling of self-esteem that the child has if he is
      accepted as he is. The surgeon seems to us like an important element in the
      dynamic of the way anxiety is dealt with since the patient and his parents
      establish a truly transferential bond to him that is of great intensity. The
      number of school problems, relational and behavioral difficulties and depressive
      reactions noted in this population shows that reconstructive surgery is very
      disorganizing for the personality and acts as a psychological trauma.

PMID- 8559850
TI  - [A transference from somewhere else: reevaluation of the controversies between
      Melanie Klein and Anna Freud (of noise and silence)].
AB  - Starting from The Freud-Klein Controversies, the author explores the historical
      reality of these controversies and their transformations into myth which give
      them the appearance of titanic fights. The verification of the different periods,
      the description of the variations in themes and style of intervention of the
      principal actors of these debates show aspects of the way a psychoanalytic
      institute works and of the theoretical elaboration in psychoanalysis: these
      appear very different from what the myth suggests. The major function of myth is,
      as Freud noted and Strachey reminds us, to hide very trite, even shameful
      realities. History and myth, theoritical effort and institutional life are all
      organized from and around transference, a major axis of psychoanalytic thought.
      When we organize our psychoanalytic lives in societies, we have the pride or the
      vanity of participating in a great historical movement. This goes back to the
      work of transference in institutional life that involves primal objects in the
      crudeness of their sexuality. Such is the constraining strength of transference.
      Being fully conscious of it, like Stratchey or Balint show us, enables to
      alleviate its violence and stimulate creativity.

PMID- 8559851
TI  - [Observation in day care centers for children and infants: reflection on the team
      role of the psychologist].
AB  - This work tempts to emphasize the relation between the quality of the reception
      of the young child and the shared observation work done by the team. It also
      tries to define the psychologist's contribution.

PMID- 8559852
TI  - [Humanitarianism: the gardener, the truck driver and the "shrink"].
AB  - The way NGO's intervene can offend "shrinks", who are attached to a slow
      temporality and suspicious of practices that are for the most part
      interventionist and that indicate the primacy of act over thought. Yet a certain
      number of people from our profession engage in "humanitarian activities", taken
      in, like others, by the effects of an illusional salvation and omnipotence. Yet
      when "shrinks" are aware of the context in which they intervene they can help
      establish alliances, create frameworks referred to a third party and seek for
      meaning. It is these three last points that seem to make their intervention most
      pertinent.

PMID- 8559853
TI  - [An update on merycism and early depression: a critical review of the literature
      and a psychopathological hypothesis].
AB  - Merycism has always intrigued clinicians. A review of the recent literature
      reminds us of its characteristics. The auto-stimulation dimension appears
      important, whatever the underlying psychopathology of mericysm. The frequence of
      mericysm during early childhood seems to have considerably diminished, even
      almost disappeared. We will discuss the reasons why mericysm continues to exist
      in the anorexic and boulmic young adult. We will analyze the relationship of
      mericysm in early childhood to depression and to growth delay. The dimension of
      ascendency seems to help us understand this problem.

PMID- 8559854
TI  - [Considerations on the diagnosis of infantile anorexia].
AB  - Authors propose a review of the international literature on infantile anorexia
      nervosa. They show that a nasographical consensus is far from being reached
      although this trouble occurs very frequently. They suggest classification axes
      which should be considered before research criteria that be used in a unified
      nosology.

PMID- 8559855
TI  - [Reaction of a young boy in early latency to the sudden death of his newborn
      brother].
AB  - Surprisingly little has been written on the impact of the death of a baby on an
      older sibling. This paper describes how a narcissistically vulnerable latency boy
      grappled, in the course of his psychotherapy, with the painful loss of his baby
      brother. Emotional and cognitive aspects of his early confrontation with the
      reality of death are considered. The patient's six theories about the cot death
      are described. Attention is drawn to the value of the sibling relationship and to
      the narcissistic needs which this relationship fulfilled. The termination phase
      is discussed in the light of the dynamics of sudden loss. The safe therapeutic
      context provided the space in which this young, rather muddled latency boy could
      grieve and mourn this traumatic loss.

PMID- 8559856
TI  - [Between life and death; a case of retrieved sudden death].
AB  - This article is about the case of a six month old baby whose parents had found
      more than twenty times in his bed almost agonizing and who had been reanimated
      each time thanks to the alarm given by a monitor. The psychotherapeutic treatment
      of the family, in the presence of the child lasted 32 sessions: this put an end
      to the respiratory and cardiac disorders and enabled a better understanding of
      the psychodynamics and the psychopathology of infancy.

PMID- 8559857
TI  - [The presence of absent persons: the identification changes of an adopted child].
AB  - Through the case study of the analytic psychotherapy of an adopted child, the
      authors illustrate the specificity of identification problems, in particular
      towards the paternal imago within an oedipal context. The transferential
      countertransferential conditions that enable to consider the psychosexual
      development, in relation to trauma and adoption, within the framework of the
      therapeutic relationship will also be considered.

PMID- 8559858
TI  - A general procedure for the estimation of interdependence.
AB  - Dependencies among observations are of interest to psychologists for both
      methodological and substantive reasons. A general procedure is developed that can
      be used to estimated dependencies among observations, given a set of a priori
      expectations about the structure of those dependencies. The utility of this
      general procedure is illustrated for specific cases: the estimation of serial
      dependency in time-series data, of dyadic and group interdependence in social
      psychology, and of reliability. The utility of the approach derives from its
      generality and from its ability to handle randomly missing data.

PMID- 8559859
TI  - Measuring ordinal association in situations that contain tied scores.
AB  - The construal of ties is critical for assessing the association between two
      variables. Ties should be excluded when the investigator's data-collection
      procedure forces ties to occur (e.g., a J-place rating scale is used to rate K
      items, with J < K; a criterion variable contains fewer than K possible outcomes
      per item). Four measures arising from excluding or including ties on 2 ordinal
      variables are Goodman & Kruskal's G, Somer's dyx, Kim's dyx, and Wilson's e. In
      contrast to measures having variance-accounted-for interpretations, probabilistic
      interpretations developed here can be applied meaningfully both to ordinal-scaled
      variables and to stronger scales. Recommendations are offered for which measure
      to use in various situations.

PMID- 8559860
TI  - Applying cognitive-social theory to health-protective behavior: breast self
      examination in cancer screening.
AB  - This article applies recent developments in cognitive-social theory to health
      protective behavior, articulating a Cognitive-Social Health Information
      Processing (C-SHIP) model. This model of the genesis and maintenance of health
      protective behavior focuses on the individual's encodings and construals,
      expectancies, affects, goals and values, self-regulatory competencies, and their
      interactions with each other and the health-relevant information in the course of
      cognitive-affective processing. In processing health information, individuals are
      assumed to differ in both the accessibility of these mental representations and
      the organization of relationships among them. In this article, the model is
      applied to analyze and integrate the often-confusing findings on breast self
      examination in cancer screening. Implications are considered for assessments and
      interventions to enhance adherence to complex, long-term, health-protective
      regimens, tailored to the needs and characteristics of the individual.

PMID- 8559861
TI  - Authoritarianism and projection.
AB  - To extend the 1995 work of McCollaum and Lester, 378 undergraduate students were
      administered the conservatism scale of the Wilson-Patterson Attitude Inventory
      and the projection scale of the Defense Style Questionnaire-40. No significant
      association was found between scores on conservatism and projection.

PMID- 8559862
TI  - Implicit memory for stimuli presented during inhalation anesthesia in children.
AB  - During general inhalation anesthesia, neutral phrases including either the color
      blue or yellow combined with one of two objects, ball or kite, were repeatedly
      presented to 36 children undergoing eye surgery. Postoperative testing with a
      coloring and two-choice task was performed to detect preferences for the colors
      and objects presented under anesthesia. No preference attributable to implicit
      memory could be demonstrated, and there was no explicit recollection of
      intraoperative events. Memory of intraoperative events occurring during
      inhalation anesthesia was not demonstrated with the present methodology in young
      children.

PMID- 8559863
TI  - Machiavellian scores of nursing faculty and students.
AB  - The purpose of the research was to identify differences in scores on
      Machiavellianism between nursing faculty and students. Measurement of
      Machiavellianism was on the Mach V Scale completed by 33 nursing faculty, 47 RN
      students completing the nursing baccalaureate, and 58 senior generic students in
      one baccalaureate nursing program. Each subject received a research packet coded
      for retrieval of the nonrespondents and reducing selection bias associated with
      large nonresponse. Analysis showed no significant difference between groups and
      none related to education, age, clinical specialty, or for (faculty and student)
      groups.

PMID- 8559864
TI  - Personality inferences drawn about abusive mothers.
AB  - This study investigated the personality inferences people draw about abusive
      mothers by having 287 subjects view videotapes of four female targets engaged in
      social discourse with other adults. Some subjects were primed beforehand to
      believe that the female targets had physically abused or neglected their child
      and other subjects viewed the tapes without being primed. Afterward, all subjects
      rated the targets' personalities using 17 bipolar trait scales and estimating the
      likelihood of six social behaviors. Analyses compared the ratings of the two
      types of abuse groups (physical abuse and neglect) with each other and with the
      unprimed control group. Analysis showed that ratings of one or both of the abuse
      groups differed from those of the control group on 10 of the 17 trait dimensions
      and four of six social behaviors. Implications are drawn about the social forces
      experienced by abusive mothers and the possible role of such forces in
      therapeutic change.

PMID- 8559865
TI  - Personality, peer influence, and use of alcohol and drugs by first-year
      university students.
AB  - A comparison of 42 male and 42 female first-year university students showed
      significant personality differences between the populations. Also, males were
      more influenced by their peers to drink alcohol than were females.

PMID- 8559867
TI  - Comments on "Alcohol use and risky sex among college students".

PMID- 8559866
TI  - Cognitive behavior therapy, relaxation training, and tricyclic antidepressant
      medication in the treatment of depression.
AB  - Outcomes of seven treatment trials comparing cognitive behavioral therapy to
      treatment with tricyclic antidepressant medication in major depressive disorder
      have been quite similar to one another. This led us to question whether treatment
      outcome in time-limited studies reflected a unique effect of cognitive behavioral
      therapy. To test the uniqueness hypothesis, relaxation training, a
      nonpharmacologic, noncognitive treatment, was chosen as a comparison for
      cognitive behavioral therapy as well as drug therapy. Treatment duration was 16
      weeks. The sample of 37 patients treated for major depressive disorder was less
      depressed than those previously studied. For both cognitive behavioral therapy
      and relaxation training, outcome of depression was superior to that of tricyclic
      antidepressant medication by endpoint analysis. The posttreatment scores on the
      Beck Depression Inventory of 82% of the group receiving cognitive behavioral
      therapy improved to a Beck Depression Inventory score < or = 9 which was not
      significantly greater than that for the group receiving relaxation training
      (73%), so a unique effect was not demonstrated for cognitive behavioral therapy.
      The outcome for tricyclic antidepressant medication (29% improved to criteria)
      was significantly worse than that for cognitive behavioral therapy. The patient's
      pretreatment initial expectancy was not predictive.

PMID- 8559868
TI  - Self-consciousness Scale: a Brazilian version.
AB  - The aim of this study was to examine the applicability of a Brazilian version of
      the Self-consciousness Scale to university students. Factorial structure,
      subscale intercorrelations, and normative data obtained with 182 subjects are
      reported. These results suggest that the proposed model of self-consciousness is
      applicable in the Brazilian culture, although some significant sex differences
      were found for two of the scales. Reliability tests and the factorial validity of
      the scale showed that this version still needs refinement to be used as a
      reliable research tool.

PMID- 8559869
TI  - Adjustment to breast cancer in couples.
AB  - Present aims were to examine differences in fulfillment of emotional and
      interactional needs between 128 breast cancer patients and 121 partners and to
      examine differences in emotional and physical adjustment outcomes using a
      multivariate model of family adjustment to illness. Intact data series were
      obtained at 7 to 10 days, at 1, 2, 3, and 6 months, and 1 year postsurgery. The
      effect of cancer accentuated a complementary pattern for both emotional and
      interactional needs. The t tests of differences between means were significant at
      all phases. The main effect of time was statistically significant for scores on
      Negative Emotions, Psychological Distress, and Psychological Well-being for both
      partners. Performance of life roles in the vocational, domestic, and social
      environments also improved significantly over time. Although perceived Health
      Status remained stable for partners, patients' perceptions improved across phases
      of illness.

PMID- 8559870
TI  - A partial replication of Lippin (1990) using the Myers-Briggs type indicator with
      a sample of female prisoners.
AB  - A sample of 108 women incarcerated in a state prison who volunteered to
      participate in an employment seminar were given the Myers-Briggs Type Indicator.
      Comparison of the distribution of types here and in Myers and McCaulley's 1985
      sample using a Selection Ratio Type Table for analysis indicated an
      overrepresentation of ISTJ, ISFJ, and ISTP. The ESFP and ESFJ types were
      underrepresented. Further analysis of the types and the relationship to criminal
      offense was not significant. Results are compared with those of Lippin from 1990.

PMID- 8559871
TI  - Comparison of scores on WISC-III and WISC--R of urban learning disabled students.
AB  - Wechsler Intelligence Scale for Children-III IQs and Wechsler Intelligence Scale
      for Children--Revised IQs of 16 preadolescents who were learning disabled, urban
      students (14 black) receiving special education services were compared. Analyses
      indicated lower mean WISC-III IQs, correlations of .57, .74, and .72 between
      scores on Full, Verbal, and Performance Scales, respectively, and significant
      correlations of .44 to .80 between respective sets of subtests. Exceptions were
      Information (.34), Similarities (.30), and Picture Arrangement (.15). These
      results suggest that the WISC-III may compare favorably with the WISC--R, if
      replicated with a substantial group.

PMID- 8559872
TI  - Preconditions for sensitivity in measuring change: visual analogue scales
      compared to rating scales in a Likert format.
AB  - In a study of preconditions of responsiveness, we examined the variances obtained
      by two different ways of responding to questionnaire items. Subjects were 168
      first-year medical students. They all completed a questionnaire of nine items.
      The original Likert-like scoring was (partially) replaced by visual analogue
      scoring in three quarters of the questionnaires. For three items the analogue
      form had a significantly greater variance than the discrete form, but no discrete
      item had a significantly greater variance than its analogue counterpart. Assuming
      that a greater variance was indicative for a greater responsiveness, our findings
      provide some support for the preferred use of analogue scales over discrete
      response categories in the measurement of changes over time.

PMID- 8559873
TI  - Coping and personality.
AB  - 146 women and 47 men were given the Eysenck Personality Questionnaire and the
      Coping Inventory for Stressful Situations. Neuroticism accounted for 37% of the
      variance in emotion-focused coping. Personality was not a substantial predictor
      of other coping strategies.

PMID- 8559874
TI  - The Multidimensional Perfectionism Scale: correlations with depression in college
      students with learning disabilities.
AB  - Interpretations of depression in children and adolescents with learning
      disabilities have tended to be neuropsychological or motivational. Some research
      has related various cognitive-behavioral constructs with depression and other
      problematic outcomes for this population. Research with nonlearning-disabled
      college students has provided correlations for scores on the Self-oriented and
      the two social scales of the Multidimensional Perfectionism Scale with those on
      depression. No such work has been done with college students having learning
      disabilities. Measures for multidimensional perfectionism, anxiety, and
      depression were administered to 110 learning-disabled undergraduate men and
      women. Analysis showed that scores on only one of the social scales of
      perfectionism were positively correlated with depression scores, and this
      relation was weaker than previously found for nonlearning-disabled students.
      Findings are discussed in terms of previous research and a motivational
      interpretation of depression in learning-disabled collage students.

PMID- 8559876
TI  - College date rape: incidence and reporting.
AB  - The present survey based on 70% returns (N = 140) of a random sample of 200 women
      at one college indicated that, although 5% had been date raped, none reported the
      rapes to authorities due to feelings of self-blame and embarrassment. That rapes
      are not reported perpetuates a self-fulfilling prophecy that rapes do not occur.
      A victim of rape may feel she is the only one and may be reluctant to become the
      exception who reports. This denial by both collage authorities and victims does
      not encourage programs for prevention and treatment.

PMID- 8559875
TI  - Operant learning (R-S) principles applied to nail-biting.
AB  - The principles of R-S learning were applied to a 32-yr.-old Caucasian woman to
      reduce the frequency and duration of fingernail-biting activity in a reversal
      replication (ABAB) research design. The undesirable behavior, fingernail-biting
      which included frequency and duration, antecedents, and setting events, was
      recorded during a 28-day study. Self-monitoring recordings indicated that anxiety
      was the most prevalent antecedent. Through the use of a preliminary questionnaire
      and interview, increase in self-awareness was judged to be most effective in the
      extinction of the undesired behavior. The systematic desensitization techniques
      of deep muscle relaxation and Transcendental Meditation were used during the
      treatment phase.

PMID- 8559877
TI  - Love-styles among Latino community college students in Los Angeles.
AB  - 145 Latino community college students enrolled in Chicano Studies classes in Los
      Angeles, California were administered a love-attitudes scale. Analysis showed
      that the mean scores and endorsement patterns were similar to those in earlier
      research on white-Latino and white-non-Latino students in the United States.
      Significant gender differences were found. Latino men scored more Ludic and
      Agapic than women. Researchers might examine the love-styles and ethnic identity
      in and out of marriage among Latinos, whites, and Asians in southern California.

PMID- 8559878
TI  - Cross-sectional age differences in the self-conceptions of adults.
AB  - 105 young, 104 middle-aged, and 96 elderly adults were asked to supply 20 answers
      to the question "Who am I." This followed previous research which has shown the
      responses of children and adolescents display an age-related increase in the
      number of abstract ideas used to answer this question. Participants of all age
      groups also used a high number of abstract ideas to characterize themselves, but
      the nature of these abstractions showed maturation-related variations in
      openness, competence, and moral integrity. This pattern of results supports Erik
      Erikson's theory of identity development in adulthood.

PMID- 8559879
TI  - Personality disorders and psychiatric symptoms in psoriasis.
AB  - Two groups of psoriatic outpatients (ns = 192 and 119) were given, respectively,
      the Million Clinical Multiaxial Inventory-II and Foulds' Delusions-Symptoms
      States Inventory. They were compared with dental (n = 192) and with general
      surgical (n = 190) patients. The psoriatic group presented clearly higher mean
      scores and frequencies on most of the personality disorder scales. On Foulds'
      inventory, psoriatic patients showed higher frequencies of neurotic and psychotic
      class allocations. A cluster analysis of personality scores provided evidence for
      4 different personality clusters of patients with psoriasis: (a) Avoidant,
      Dependent, Schizoid, and Self-defeating (32.2%), (b) Compulsive, Narcissistic,
      and Aggressive (30.7%), (c) no personality disorder (18.2%), (d) Borderline,
      Paranoid, and Schizotypal, etc. (18.8%).

PMID- 8559880
TI  - Pretense and hidden feelings in the Humane Society environment: a source of
      stress.

PMID- 8559881
TI  - Performance anxiety among professional musicians in symphonic orchestras: a self
      report study.
AB  - 155 of 650 professional musicians playing symphonic orchestras in The Netherlands
      completed a self-report questionnaire concerning performance anxiety. 91 of the
      155 respondents reported experiencing or having experienced performance anxiety
      seriously enough to affect their professional or personal lives. There appeared
      to be no difference in prevalence between men and women. Substantial percentages
      of the anxious musicians reported considerable anticipation anxiety days (36%),
      weeks (10%), or even months (5%) prior to a performance. The results indicate
      that performance anxiety is a significant professional problem. It is suggested
      that teaching explicit coping strategies should be incorporated in the curricula
      of schools of music.

PMID- 8559882
TI  - Did Freud misinterpret reported memories of sexual abuse as fantasies?
AB  - While serious questions have arisen concerning the validity of Freud's seduction
      theory of neurosis, a related issue concerns the extent to which Freud, following
      the abandonment of the seduction theory, may have misinterpreted real memories of
      sexual abuse as imaginary. Certain theoretical statements by Freud as well as his
      advice to Jung concerning a 6-yr.-old patient who had accused her foster-father
      of sexual abuse indicate that he may have been significantly biased toward
      interpreting certain types of incest allegations as fantasies. Increased
      awareness of Freud's biases, both in his early tendency to pressure patients into
      believing that they were victims of abuse and in his later tendency to regard
      certain types of incest allegations as unreal, may contribute to a more objective
      approach to the diagnosis and treatment of sexual abuse in the future.

PMID- 8559883
TI  - Willingness to work with and sympathy for HIV-positive coworkers: an experimental
      examination of mode of transmission concern, and knowledge.
AB  - This study investigated concern about HIV infection, knowledge about HIV/AIDS,
      and mode of transmission on willingness to work with and sympathy expressed
      towards a coworker with AIDS. 120 undergraduate students were randomly assigned
      to one of 12 groups in a 3 x 4 between-subjects design. Subjects viewed one of
      three 12 min. videotapes, including one videotape designed to increase concern,
      one designed to increase information, and a control videotape of music.
      Participants then read one of four scenarios about training a new employee. The
      scenarios varied the mode of HIV transmission (unknown, heterosexual contact,
      homosexual contact, or blood transfusion). Analysis showed that the ratings of
      willingness to work with or sympathy toward the HIV-positive coworker made after
      the videotape were not higher than those of other groups; however, significantly
      greater sympathy was reported for coworkers with unknown means of transmission
      than for coworkers who had contracted the virus through homosexual activity and
      more sympathy was also shown for coworkers who had contracted AIDS through blood
      transfusion than for employees who became infected through any type of sexual
      activity. Findings are discussed in terms of the AIDS literature and suggestions
      for employers.

PMID- 8559884
TI  - Seclusion in treatment of adolescents on an acute inpatient unit.
AB  - Seclusion practices on a unit of adolescent inpatients with acute problems are
      compared with those in Norway on an innovative unit for adults. Research into the
      effectiveness of such programs is discussed.

PMID- 8559885
TI  - Effects of drinking by the victim or offender on verdicts in a simulated trial of
      an acquaintance rape.
AB  - College students, 232 women and 151 men, read a simulated trial of rape by an
      acquaintance under one of four conditions: victim only drinking, offender only
      drinking, and both drinking or neither drinking before the alleged assault. How
      much students blamed the victim or offender for what happened and their verdict
      were unaffected by these conditions. Yet students rated alcohol consumption as
      having contributed to the alleged assault. Apparently, they simply did not
      attribute blame to consuming alcohol. How much students blamed the victim and the
      offender and having been or having known a rape victim predicted jurors' verdicts
      with 89% accuracy.

PMID- 8559886
TI  - Case outcomes in domestic violence court: influence of judges.
AB  - Observation of 174 domestic violence cases in a civil court indicated that the
      only significant factor related to case outcomes was the judge hearing the case.
      The three judges whose cases were observed differed significantly in their rates
      of cases dismissed, findings for or against the respondents, and number and types
      of orders issued. The data suggest the need for more consistent education of
      judges in regard to domestic violence.

PMID- 8559887
TI  - Use of the Rorschach in planning psychotherapy.
AB  - Research has shown that the Rorshach can be used to identify people who benefit
      from psychotherapy; the critical variable in that assessment is form level. One
      way of looking at form level is as a reflection of ego strength, and one can
      conclude that the level of ego strength and all of the implications regarding
      information-processing, meaning-making, and the capacity for logical and
      realistic thinking would, then, seem to be associated with benefiting from
      psychotherapy. This finding was extended to suggest that this Rorschach
      assessment of ego strength is related to the kind of psychotherapy a person might
      or should be offered; that is, whether it should be supportive or exploratory or
      short-term and problem-centered. Rorschach data can also be helpful in
      identifying whether treatment-disruptive transferential reactions or resistances
      exist. In light of the information which can be gleaned from the Rorschach, it
      seems reasonable to suggest that the Rorschach should be used routinely in the
      planning of psychotherapy.

PMID- 8559888
TI  - Survivors' trauma and departmental response following deaths of police officers.
AB  - It was hypothesized that satisfaction with supportive reactions of the police
      department following the on-duty death of an officer helps to ameliorate
      traumatic stress in surviving spouses. This hypothesis is based on the premise
      that the police-work group is cohesive and provides a psychological safety net
      for the surviving spouse. A secondary analysis was conducted of data obtained
      from 162 surviving police spouses. Analysis indicated that spouses' reported
      satisfaction with the department was significantly associated with lower trauma
      stress scores. These findings suggest that police departments should formulate
      policy to provide assistance to spouses surviving duty-related police deaths.

PMID- 8559889
TI  - Aging and sense of control.
AB  - Three groups representing different phases of the developmental lifecycle--12
      senior citizens, 67 young adults, and 14 healthy middle-aged normal adults--were
      assessed using a multidimensional control inventory. Senior citizens had a
      healthy over-all sense of control comparable to those of the other two groups and
      a significantly lower (healthier) negative sense of control. They also were
      significantly more likely to endorse acceptance as a way of addressing areas of
      concern and to complement self as a source of control with a sense of control
      coming from others (including God, belief in a higher power).

PMID- 8559890
TI  - Correlations of grade point averages at a rural college with reports of abuse in
      rural families.
AB  - The possible influences of intrafamilial conflict and emotional physical, and
      sexual abuse were examined in relation to academic achievement in college. 135
      students of a small private university in a rural setting responded to a
      questionnaire. Reported histories of sexual abuse and physical abuse by family
      members wee associated with lower mean grade point averages. Individuals who
      reported occasional emotional abuse had a lower mean grade point average than
      those who reported frequent or no emotional abuse. Treatment implications and
      directions for research should be considered.

PMID- 8559891
TI  - Using the Multiphasic Sex Inventory with child molesters.
AB  - Subjects were 30 white men who denied that they were child molesters at the time
      of arrest and were court ordered to have a psychological evaluation as part of
      the pre-sentencing. The Multiphasic Sex Inventory was administered to the
      subjects during the initial interview and later in therapy sessions they did
      admit to the offense. When scores for the group were compared with scores for a
      pretreatment child-molester group (n=140) in a study cited in the manual, the
      difference was significant on the Child Molest Lie Scale. Implications are
      discussed.

PMID- 8559892
TI  - Birth order, family environment, and young adults' occupational aspirations.
AB  - Relationships were examined among birth order, family environments, and
      occupational aspirations for 320 21-yr.-old Australians. The results indicated
      that relations between birth order and aspirations were mediated by associations
      between the young adults' perceptions of their parents' involvement in learning
      and the measures of aspiration.

PMID- 8559893
TI  - Social skills of persons with self-defeating personality.
AB  - 55 undergraduate men and 55 women took Schill's 1990 Self-defeating Personality
      Scale and Lorr, Youniss, and Stefic's (1991) multidimensional Social Relations
      Survey. As expected, persons who endorsed more self-defeating characteristics
      scored lower on scales which make up the Social Skills or Assertiveness Factor.
      However, these scores did not have significant correlations with the Empathy or
      Social Approval Need Scales; two of the three scales which make up the Empathy
      Factor. The results were discussed in terms of prior work relating deficits in
      social skills to dysfunctional early parenting.

PMID- 8559894
TI  - Scores of Brazilian University students on the Beck Depression and the State
      Trait Anxiety Inventories.
AB  - The profiles of the Beck Depression Inventory and State-Trait Anxiety Inventory
      scores were obtained for a sample of Brazilian university students and compared
      with those of other studies. Subjects were 270 students from various universities
      in Sao Paulo, age 23.8 yr. (SD=6.7 yr.). The mean Beck score for the total sample
      was 8.5 (SD=7.0); according to the cut-off score of 16, 86.9% were considered
      normal, 7.5% had scores compatible with dysphoria, and 5.6% had scores indicative
      of depression. The mean State-Trait Anxiety score for the total sample was 40.7
      (SD=8.6). Considering one standard deviation as the threshold point, 17.8%
      published data indicated that the Portugese versions of the questionnaires are
      equivalent to original versions.

PMID- 8559895
TI  - Prevalence of depression among middle-school Kuwaiti students following the Iraqi
      invasion.
AB  - The prevalence of depression among 1981 middle-school students (995 boys and 986
      girls) in Kuwait was estimated using the Arabic Children's Depression Inventory.
      Cronbach coefficients alpha for their scores were .86, .88, and .87, for boys,
      girls, and the combined group, respectively. There were 3.7% of boys and 4.8% of
      girls who attained total scores greater than 2 SDs above the mean. It was noted
      that subjects who have a martyr or a POW in the family exhibited a significant
      difference on depressive symptoms. The boys obtained a mean of 44.2 whereas the
      girls obtained a mean of 42.5. Further, there was a significant correlation
      between scores on depression and report of stressful experience. An
      interpretation of this finding was provided.

PMID- 8559896
TI  - Preventing relapse in weight control: a discussion of cognitive and behavioral
      strategies.
AB  - Weight maintenance is the most difficult part of weight control. People who diet
      and regain weight often experience negative physiological effects and lowered
      self-esteem each time they regain weight. This suggests the need for successful
      weight maintenance programs. Health-care professionals can develop and implement
      maintenance programs using cognitive and behavior-change strategies which include
      ways to cope with relapse. This paper describes the physiological and emotional
      problems associated with weight maintenance and explores the use of cognitive and
      behavioral concepts in addressing these issues.

PMID- 8559897
TI  - Measuring workaholism: content validity of the Work Addiction Risk Test.
AB  - A total of 20 psychotherapists, randomly selected from a state list, critically
      examined the 25 items on the Work Addiction Risk Test for content validity.
      Subjects were asked to identify 25 items from a list of 35 which most accurately
      measured work addiction. Selected test items have generally high content validity
      for the domain of work addiction.

PMID- 8559898
TI  - Development and psychometric validation of the Mental, Physical, and Spiritual
      Well-Being Scale.
AB  - Due to the growing interest in holistic health and well-being, the Mental,
      Physical, and Spiritual Well-being Scale was developed. This well-being scale has
      30 items and incorporates mental, physical, and spiritual subscales. An initial
      set of items was developed and 186 university students responded to these. An
      exploratory factor analysis was conducted using principal components analysis
      with varimax rotation (N=100) to reduce the number of items in the scale. Three
      factors were extracted based on the eigenvalues, loading coefficients exceeding
      0.3, and the screen test. Ten items from each of the three factors were selected,
      reducing the number of items from 66 to 30. Another factor analysis, performed on
      129 employees of the Commonwealth Scientific and Industrial Research Organisation
      and 229 students from Monash University, indicated three factors were
      representative of the mental, physical, and spiritual subscales. Test-retest
      reliabilities over 1 mo. ranged from 0.87 to 0.97 for the three subscales whilst
      internal consistency ranged from 0.75 to 0.85. Concurrent validity was examined
      using the General Health Questionnaire and the Spiritual Well-being Scale. The
      discriminant validity of the MPS was also explored using three activity groups
      nominated as highly physical (weight training) or highly mental (chess) or highly
      spiritual (prayer). Out of a total of 88 cases, 77.3% of these were correctly
      classified into their actual activity group based on their scores. Sample sizes
      were moderate and testing was of limited samples. More psychometric work is
      needed but preliminary findings indicate an accurate and reliable test.

PMID- 8559899
TI  - Alcohol consumption and health: synergistic interaction with personality.
AB  - In this study, 6,386 males and 5,990 females, with a mean age of 55 years,
      constituting a random sample, were administered questionnaires by interviewers
      relating to amount of self-regulation and drinking status. They were then
      followed up over a 20-yr. period, and health status (living well, chronically
      ill, or deceased) was ascertained. It was hypothesized that the deleterious
      effect of alcohol would be worse for those low on self-regulation; that health
      status would be worse for those in whom drinking diminished self-regulation, as
      compared with those for whom drinking improved self-regulation; and that smoking
      would have greater effects in lowering health status in those in whom drinking
      diminished self-regulation than in those in whom drinking improved self
      regulation. All predictions were borne out by the data at high statistical
      significance. The results confirmed findings from an earlier study to the effect
      that psychological factors like self-regulation powerfully influence the kind of
      effects drinking has with respect to health.

PMID- 8559900
TI  - Trends in police suicide.
AB  - Little empirical information is available concerning trends of suicide by police
      officers. Anecdotes and articles in the popular press imply that the rate is
      increasing but do not provide a scientific base. Data from an epidemiological
      mortality database are used to describe trends in police suicide in a medium
      sized police department over a 40-yr. period.

PMID- 8559901
TI  - Relationship between the Quick Test and WAIS-R in low-functioning criminal
      defendants.
AB  - Quick Test and WAIS-R scores of 30 low-functioning criminal defendants were
      compared. Analysis indicated that the Quick Test (even 1 form) genetically
      provides an accurate estimate of WAIS-R IQ in this population.

PMID- 8559902
TI  - Self-actualization and empathy as predictors of marital satisfaction.
AB  - The relationships between marital satisfaction, self-actualization, and empathy
      scores were tested for 30 intact couples. Analyses indicated that both
      satisfaction and empathy scores were independent predictors of marital
      satisfaction scores for men, but not for women. Implications were discussed.

PMID- 8559903
TI  - Patterns of adjustment among women with breast cancer and their partners.
AB  - Four inventories were completed by 128 women and 121 partners evaluating
      predictors of emotional and physical adjustment at six phases of experience with
      breast cancer. Emotional adjustment could be predicted by marital support,
      support from other adults, and role function. The relationships were significant
      at concurrent times, across contiguous times, and predicting from the 7- to 10
      day postsurgical phase to both the 6-mo. and 1-yr. end points.

PMID- 8559904
TI  - Psychological screening of impotence with Finney's MMPI-derived Impotence Scale.
AB  - Three groups of patients in treatment were assessed for impotence, using MMPI
      derived Impotence Scale. Group I were 46 patients who had been screened and
      scheduled for a penile prosthesis when the impotence resulted from known organic
      causes (biogenic). Group II were 198 patients in a sexual dysfunction clinic, for
      whom biogenic causes had been ruled out (psychogenic). Group III were 51
      substance abusers in drug rehabilitation. While scores on the Impotence Scale did
      not distinguish between the biogenic and psychogenic groups, the scores were
      almost three times higher than average scores among subjects in the
      standardization sample. MMPI-derived Impotence Scale scores were similarly
      elevated among the substance abusers. Results suggest that the Impotence Scale
      may serve as a useful screening tool to alert clinicians to the possibility of
      erectile dysfunction for which further clinical evaluation would be required.

PMID- 8559905
TI  - Comment on the inpatient treatment of mood disorders.

PMID- 8559906
TI  - Evaluation status, educational setting, and behavior ratings of students with
      serious emotional disturbance.
AB  - 60 students' files were randomly selected from a pool of 308 who were designated
      as seriously emotionally disturbed by their school districts. Analysis indicated
      that n = 30 students receiving their initial evaluations were rated more
      negatively by their special education and homeroom teachers than those 30 being
      reevaluated. Compared with the 60 special education teachers, more negative
      ratings were given by the 60 homeroom teachers. Elementary and secondary school
      placement did not significantly affect the behavior ratings.

PMID- 8559907
TI  - Cold-induced amnesia blocks escape deficits in the cockroach (Periplaneta
      americana).
AB  - For three consecutive days, four groups of adult cockroaches (Periplaneta
      americana) were yoked to cockroaches receiving escapable shock. The four groups
      of subjects received either inescapable shock followed by exposure to 12 minutes
      of cold (2 degrees C), inescapable shock followed by no exposure to cold, no
      shock followed by exposure to cold, or no-shock followed by no exposure to cold.
      24 hr. later all five groups were run on a different escape task. The cockroaches
      exposed to inescapable shock followed by no exposure to cold showed the usual
      escape deficit. The cockroaches exposed to inescapable shock followed by exposure
      to cold did not alter from the escapable shock cockroaches or the controls.

PMID- 8559908
TI  - Neuropsychological principia brevita: an application to traumatic (acquired)
      brain injury.
AB  - The concepts and discoveries of modern neuroscience now challenge many of the
      presumptions that influence diagnostic decisions within neurology, psychiatry,
      and clinical neuropsychology. Many of these presumptions are derived from archaic
      bivariate models such as the mind-body argument, organic-functional dichotomy,
      and single lesion-single behaviour causality. Thirteen basic principles which may
      be useful for inferring more reliable and accurate relationships between
      microstructural function an clinical manifestations are developed.

PMID- 8559909
TI  - Childhood psychopathology and nonintact family status in South Africa.

PMID- 8559910
TI  - Self-esteem and alexithymia.
AB  - 236 college students completed Coopersmith's Self-esteem Inventory and Taylor's
      20-item Toronto Alexithymia Scale. As predicted, the total scores on self-esteem
      and alexithymia were significantly negatively correlated-.42. Two factors of the
      subjects' orientations of alexithymia, difficulty recognizing and verbalizing
      feelings and difficulty describing feelings, explained 19% of the variance
      associated with self-esteem. These results suggest a negative association between
      difficulty in expressing emotions and college student's self-rated self-esteem.

PMID- 8559911
TI  - Psychometric measures of trauma among psychiatric patients reporting ritual
      abuse.
AB  - Increasing reports by psychiatric patients of ritual abuse have provoked a debate
      about the appropriate interpretation of such allegations. Some authors contend
      that these claims represents fantasy material, dissimulation, or delusions.
      Others maintain that patients' descriptions of ritualized trauma may constitute a
      newly identified psychiatric syndrome. The present investigation compared
      psychometric measures of trauma, the MMPI-2 PK and PS scales, in a group of
      patients reporting ritual abuse and another group with no such accounts of ritual
      abuse. Comparisons were statistically significant with mean PK and PS scores of
      86.3 and 85.8, respectively, for the 34 reporting ritual abuse and 58.3 and 58.7
      for the 31 not reporting ritual abuse. Further, 91% of the patients alleging
      ritual abuse had scores on at least one of the two scales within the clinical
      range, i.e., T score > or = 65. It was concluded that patients reporting
      histories of ritual abuse also showed significantly elevated scores on these
      scales and their scores were higher than those obtained for a sample of patients
      not reporting ritual abuse.

PMID- 8559912
TI  - Retrospective self-reported symptoms of attention-deficit hyperactivity disorder:
      reliability of the Wender Utah Rating Scale.
AB  - We measured the internal consistency and four-week temporal consistency and
      temporal stability of the Wender Utah Rating Scale and its 25-item short form.
      The Wender scale is a rationally constructed retrospective self-report rating
      scale for symptoms of Attention-deficit Hyperactivity Disorder. Both scales
      manifested excellent internal consistency. Over one month, both versions
      manifested significant temporal consistency and good temporal stability in the
      nonclinical sample of 83 successful young adults most likely to be referred for
      an evaluation of suspected Attention-deficit Hyperactivity Disorder. The
      collegiate group had a considerably higher Wender score than the original
      normative group, calling into question the adequacy of the limited normative
      data. However, both forms of the scale are reliable and comprehensive validation
      research is advocated.

PMID- 8559913
TI  - Narcissism and Machiavellianism.
AB  - Associations of Machiavellianism and narcissism were examined in two samples (Ns
      = 214 and 205) via the Mach-IV and the Narcissistic Personality Inventory. Scores
      on these self-report measures were correlated. Machiavelianism scores were
      positively associated with aspects of narcissism which indicate maladjustment,
      i.e., entitlement and exploitativeness, and inversely associated with adaptive
      narcissistic tendencies, i.e., self-sufficiency. The discussion focuses on the
      relative adjustment of those scoring high on Machiavelianism.

PMID- 8559914
TI  - Severity of alexithymia is related to psychosocial factors in patients with
      peritoneal dialysis.
AB  - We examined the relationship between alexithymia and psychosocial factors in 72
      peritoneal dialysis patients. The 72 patients had significantly higher scores on
      alexithymia and anxiety than did 73 healthy volunteers. The alexithymia scores
      were significantly and positively correlated with anxiety scores, suggesting that
      alexithymia may be related to anxiety derived from the stress associated with
      dialysis therapy. After 3 yr. of follow-up consultations, patients were still
      showing higher scores on alexithymia and anxiety; however, alexithymia scores
      were not correlated with anxiety scores but rather were significantly associated
      with poor social support. Alexithymic characteristics may be related to
      psychosocial factors such as the availability of social support.

PMID- 8559915
TI  - Identifying the relationship between work and nonwork stress among bank managers.
AB  - The purpose of this study was to (1) test the effects of various demographic and
      socioeconomic variables on perceived stress among bank managers in both work and
      nonwork environments and (2) to ascertain whether the correlation is significant
      between perceived stress in the work and nonwork environments among the same bank
      managers. Significant differences were found between genders, among management
      levels, and among age groups. A multiple linear regression test showed a positive
      relationship between perceived stress at work and away from work.

PMID- 8559916
TI  - Psychology of computer use: XXXIV. The Computer Hassles Scale: subscales, norms,
      and reliability.
AB  - Data from 1199 students users formed the normative database for the Computer
      Hassles Scale, a 37-item measuring computer users' stress. The Computer Hassles
      Scale was scored to yield a severity of hassles score for the total scale and two
      subscales, Computer Runtime Errors and Computer Information Problems. The total
      scale and both subscales showed high internal consistency as measured by the
      Cronbach coefficient alpha. Guidelines for identifying high and low severity of
      computer users' stress were suggested.

PMID- 8559917
TI  - Retrospective appraisals of fathers' effectiveness and psychological health of
      adults.
AB  - Previous research has shown fathers' self-reports of their effectiveness to be
      positively correlated with their children's psychological health. To assess the
      relationship between adults' retrospective appraisals of fathers' effectiveness
      using a modified version of the Seven Secrets Survey and rated their current
      psychological health on the Personality Assessment Questionnaire. Total scores on
      the two measures correlated - .37. Three of the six Seven Secrets Survey scales,
      Knowing your Child, Consistency, and Protecting/Providing, were also correlated
      with total scores on the Personality Assessment Questionnaire.

PMID- 8559918
TI  - Use of smokeless tobacco by Mexican-American high school students.
AB  - A survey of 208 girls and 191 boys attending a public high school in southwestern
      New Mexico was conducted to examine students' use of smokeless tobacco products.
      One Mexican-American girl identified herself as a user of chewing tobacco. Of the
      boys 8% (17) indicated that they used chewing tobacco and 7% (15) reported that
      they dipped snuff. 6% (12) indicated use of both snuff and chewing tobacco. The
      boys included 153 Mexican-Americans of whom 7% used smokeless tobacco and 26
      Anglo-Americans of whom 34% were users.

PMID- 8559919
TI  - Psychosocial effects of skin treatment with Imedeen.
AB  - In a 3-mo. randomized double-blind placebo-controlled study, the psychosocial
      effects of the food supplement IMEDEEN on health-specific quality of life were
      examined. Participants were 45 Caucasian women with a normal skin condition in
      relation to their age. The variables measured were social anxiety and social
      skills, self-esteem, satisfaction with several parts of the body, state and trait
      anxiety, and psychological and social problems related to the skin. No
      significant effect of IMEDEEN was found on any of these psychosocial variables.
      Suggestions for further research are given.

PMID- 8559920
TI  - Gender differences in teachers' behaviors in relation to adolescents' self
      concepts.
AB  - Gender differences in the relationship between teachers' behaviors and
      adolescents' self-concepts were investigated in 276 (156 boys and 120 girls)
      Standard Ten students from two coeducational high schools in Langa, Cape Town,
      South Africa. The Perceived Teacher Behavior Inventory was used to measure
      adolescents' self-concepts. Analysis indicated significant differences in
      perceived teachers' behavior and adolescents' self-description scale scores
      between boys and girls. Further, students' self-concept dimensions most strongly
      associated with teachers' behaviors were relations with family, general school,
      and health.

PMID- 8559921
TI  - Differences in attitudes among medical students towards psychiatry in one English
      university.
AB  - Responses of 146 medical students in the final academic year on the Attitudes
      Towards Psychiatry Questionnaire were obtained before and after the clerkship in
      psychiatry. While there were no significant differences between the 57 men and 89
      women, students' image of psychiatrists did not change but several initially held
      attitudes about psychiatric practice and training improved following the
      clerkship.

PMID- 8559922
TI  - Importance of central issues and students positive evaluation of life events.
AB  - To increase our understanding of stress-resistance factors in college students,
      we examined whether the importance attached to certain issues would distinguish
      among 123 students who evaluated recent stressful life events positively or
      negatively. For a subsample of undergraduate students, 16 positive evaluators
      considered Intimacy and Adventure less important than 24 negative evaluators.

PMID- 8559923
TI  - Dilemmas associated with rehousing homeless people who have companion animals.
AB  - 66 individuals were given a questionnaire during the initial visit to a
      veterinary clinic for homeless pet owners. Among the 35 men and 31 women, 32 had
      been homeless for 6 mo. or less and were termed the acutely homeless subgroup,
      and 34 had been homeless multiple times or for more than 6 mo. and were termed
      the chronically homeless subgroup. In responding to the Lexington Attachment to
      Pets Scale, both men and women participants had significantly higher mean scores
      on attachment to their pets than did the scale's standardization population.
      Participants did not differ from the normative sample of adults on the Beck
      Hopelessness Scale. Both men and women participants stated a preference for being
      rehoused. 93% of men and 96% of women said that housing would not be acceptable
      if pets were not allowed. 61% of the men and 33% of the women stated they would
      be willing to live anywhere pets were allowed except in a shelter. Reluctance to
      live in a shelter was significantly greater among chronically homeless men than
      other subgroups, and they also had low desire to be rehoused. A majority of the
      participants had been refused housing because they had pets. Attempts to rehouse
      homeless individuals who have pets are likely to be unsuccessful unless
      accommodation for pets is included.

PMID- 8559924
TI  - College depression: causes, duration, and coping.
AB  - Analysis of 149 responses (based on a 15% random college sample) indicated that
      90% considered they were or had been depressed at college. Depression was usually
      moderate and of short duration and associated with boyfriend/girlfriend
      difficulties, other social adjustment, and grades. These students turned to
      friends, themselves, and parents for help. Treatment could be provided by a
      college.

PMID- 8559925
TI  - Measuring social desirability among senior medical students.
AB  - The purpose of the study was to assess the role of medical students' social
      desirability scores on influencing their attitudes toward either a geriatric or
      hypochondriac patient. To carry out this investigation, we developed a social
      desirability scale that was domain-specific for medicine. Students' medical
      social desirability scores predicted negative attitudes and beliefs toward the
      geriatric but not the hypochondriac patient. This difference suggests that
      medical students find it acceptable to dislike the hypochondriac as a patient but
      not the elderly person. Social desirability scores were inversely related to
      Machiavellan scores, suggesting that medical students with a Machivellian
      response pattern tended to view their role as a physician in a less idealized
      way. Students who scored highest on social desirability tended to choose
      obstetrics-gynecology for their future career and those with the lowest scores
      either pathology or surgical subspecialties. Research with this scale should help
      access social desirability's role in medical students' in managing the impression
      they leave with patients.

PMID- 8559926
TI  - Measurement of social interaction in change of health behavior.
AB  - A social network approach to measuring social interaction related to change of
      health behavior required 460 participants in a health promotion program to
      nominate up to five network members and to rate the supportiveness of each person
      in changing health behavior during the previous year. Exploratory factor analysis
      of intercorrelations of the eight items suggested two factors representing
      supportive and negative interaction with internal consistency reliability of .89
      and .61, respectively.

PMID- 8559927
TI  - Factors that influence professional employees willingness to seek counseling.
AB  - 120 MBA students in a program with a professional work experience component
      completed a survey in which they were asked whether they would seek counseling
      under different sets of circumstances. Respondents were more likely to seek
      counseling when they were looking for general career counseling or when their
      employer insisted on the counseling and when they did not have to pay for the
      counseling themselves.

PMID- 8559928
TI  - Ethnic differences on the Outcome Questionnaire.
AB  - The Outcome Questionnaire is a 45-item inventory of client-report symptoms and
      distress, used to track therapeutic change on a session-by-session basis. Data
      collected with the cooperation of a managed care provider were analyzed to note
      ethnic differences on the questionnaire. 1552 first session questionnaires were
      selected and mean total and subscale scores were analyzed using analysis-of
      variance procedures for differences by ethnicity. No significant differences were
      found; however, significant ethnic differences on some items were noted, and
      these are reported with ethnic trends in clients' problems, diagnoses, and
      therapists' ratings on Global Assessment of Functioning. These findings were
      contrasted with those of other studies reporting ethnic differences on various
      measures such as IQ and personality assessment.

PMID- 8559929
TI  - Self-critical depressive experience in posttraumatic stress disorder.
AB  - Consistent with prior research, 73 hospitalized male Vietnam veterans with combat
      related Posttraumatic Stress Disorder (PTSD) reported high scores on Self
      criticism as measured by the Depressive Experiences Questionnaire. Self-criticism
      scores predicted greater severity of PTSD (Mississippi scale) after controlling
      for symptomatic depression (MMPI-D scale), suggesting that the nature of
      depression in Posttraumatic Stress Disorder differs from that in major depressive
      disorder.

PMID- 8559930
TI  - Self-esteem, compliance, and cervical screening.
AB  - A computerized version of the semantic differential was administered to 57
      respondents and 43 nonrespondents to invitations for a cervical smear test. 26
      concepts pertaining to emotional, social, parental, and health-related domains
      were tested. The semantic differential was followed by a personal questionnaire.
      Analysis indicated that fear, worry, and embarrassment were negatively correlated
      with the decision to have a cervical smear test. Respondents seemed to have
      higher self-esteem and better relationships with their husbands than
      nonrespondents.

PMID- 8559931
TI  - Time perspective of substance abuse patients: comparison of the scales in
      Stanford Time Perspective Inventory, Beck Depression Inventory, and Beck
      Hopelessness Scale.
AB  - This study examined the correlations between the Stanford Time Perspective
      Inventory, the Beck Depression Inventory, and the Beck Hopelessness Scale for an
      in-patient substance-abuse population of 50. Analysis did not support the
      hypothesis that substance abusers would be more likely to be present-hedonistic
      and present-fatalistic rather than past- or future-oriented. However, the results
      modestly supported the hypothesis that future orientation would be negatively
      correlated with scores on depression and hopelessness measures. In this sample,
      there was a slight tendency toward the time orientations of future- and present
      fatalistic. Correlations among scores on the three measures were generally low
      (range = .06 to -.38).

PMID- 8559932
TI  - Changes in national suicide rates, 1980-1990.

PMID- 8559933
TI  - Creativity, depression, and circannual variation.
AB  - Verbal creativity has been linked to personal and family histories of bipolar
      depression. The present studies investigated the relationship between creativity
      and atypical symptoms of bipolar depression such as seasonal mood variations.
      Although more creative individuals, as measured by scores on the Remote
      Associates Test and a writing sample, perceived seasonal fluctuations in their
      creativity, no significant differences in performance were found.

PMID- 8559934
TI  - An ego-psychological approach to the Rorschach.
AB  - This presentation is an extension and amplification of the ego-psychological
      assessment of Rorschach data initiated in 1946 by Rapaport, Gill, and Schafer
      whose focus was on the quality of the perception of reality and the assessment of
      defence. A more contemporary view of ego psychology not only includes an expanded
      view of defence but also of the nature of self- and object representations and
      the nature of object relations. An assessment of the synthesizing function of the
      ego was also discussed. The present purpose was to present a comprehensive
      assessment of Rorschach data from the point of view of contemporary ego
      psychology.

PMID- 8559935
TI  - Questionnaire format bias: when are juxtaposed scales appropriate: a call for
      further research.
AB  - This study examined the use of juxtaposed scales, a type of self-report response
      scale used to study numerous attitudinal and behavioral concepts. This research
      is an extension of the exploratory work on the bias associated with juxtaposed
      scales begun by Hunt and Miller in 1983. Findings support the hypothesis that
      juxtaposed scales will elicit different responses than separate scales. When are
      these differences explicit and when are they an unwanted bias? Results and
      attendant discussion and recommendations are used to call attention to the
      importance of planning for the method bias which can be created by the use of
      juxtaposed scales.

PMID- 8559936
TI  - Suicide, homicide, and a history of oppression in the Caribbean nations.

PMID- 8559937
TI  - Applicability of the goodness-of-fit hypothesis to coping with daily hassles.
AB  - This study examined the applicability of Lazarus and Folkman's (1984) goodness-of
      fit hypothesis to the relationship between college students' daily hassles and
      psychological symptomology. Specifically, the model predicts that, given a daily
      hassle which one may change, it is more functional to alter the source of the
      daily hassle than it is to let the stressor go unchecked and simply try to manage
      the negative emotions produced by the event. Conversely, given a stressor one
      cannot alter, it is more functional to regulate the emotions produced by the
      event than to engage in repeated futile attempts to change an uncontrollable
      stressor. It was predicted that subjects who tended to violate these principles
      across multiple daily hassles would be characterized by the highest psychological
      symptomology. Although the 69 college students' frequency of daily hassles was
      positively associated with psychological symptomatology and students tended to
      match the method of coping with the appraised controllability of their daily
      hassles, no support for the goodness-of-fit hypothesis was found.

PMID- 8559938
TI  - Infant mortality in Caucasians and African Americans.

PMID- 8559939
TI  - Gender differences of reported safer sex behaviors within a random sample of
      college students.
AB  - This study investigated the frequency of safer sex behaviors with a random sample
      of sexually active college students (N = 315) at a university in the Northwest.
      The most frequent safer sex behaviors were discussion of contraceptives (58.6%),
      being more selective (46.5%), and reducing the number of sexual partners (43.6%).
      The least frequent safer sex behaviors included discussion of partner's sexual
      health prior to sexual behavior (26.1%), using condoms or dental dams (24.4%),
      one sexual partner (22.6%), and abstaining from sex as a safer sex practice
      (12.3%). The only two behaviors which indicated gender differences were (a) if
      they were being more selective as a safer sex practice and (b) reducing number of
      sexual partners as a safer sex practice. Women were more likely to state that
      they were " almost always" more selective than their male peers. Findings from
      this study indicated that a substantial number of students reported "risk
      factors" sexual practices. These findings indicated a need for HIV-prevention
      efforts.

PMID- 8559940
TI  - The pleasures and problems of hearing dog ownership.
AB  - Emotional aspects of owning hearing dogs were explored in 38 hearing-dog owners
      and a control group of 23 prospective owners. Both groups listed companionship
      and hearing assistance as pleasant reasons for owning such dogs. Having a dog and
      personal independence were reasons mentioned only by prospective owners. Both
      groups mentioned travel complications as unpleasant problems. Owners referred to
      dogs' behavior problems significantly more often than did prospective owners who
      appeared to have unrealistic expectations that dog ownership would be problem
      free.

PMID- 8559941
TI  - Self-perceived traumatic stress in college: a survey.
AB  - Most studies of Posttraumatic Stress Disorder have involved war veterans and
      victims of natural disasters and violent crime. To evaluate the incidence at
      college, 179 college students' responses were examined. Analysis indicated that
      there was a high frequency of self-perceived traumatic stress in this sample; 42%
      reported traumatic events, whereas only 6% would meet strict diagnostic criteria.
      Automobile accidents, deaths, and harassment were events perceived as traumatic.
      Most students turned to themselves or friends for treatment. Apparently traumatic
      events are more prevalent on campus than previously thought and (with the
      exception of rape) are rarely covered in prevention programs. College health
      authorities should be aware of the high incidence of perceived trauma, inform
      college students of potential stressors, and provide appropriate treatment.

PMID- 8559942
TI  - Vulnerability Scale scores in female inpatients diagnosed with self-injurious
      behaviour, dissociative identity disorder, and major depression.
AB  - For three groups of predominantly female inpatients scores on the Glover
      Vulnerability Scale were compared with each other and with those of a control
      sample. The four groups included individuals who were diagnosed with self
      injurious behavior, females diagnosed with Dissociative Identity Disorder,
      females whose predominant diagnosis was Major Depressive Disorder, and female
      controls. Females with a trauma-related diagnosis (Groups 1 and 2) scored higher
      on the Glover Vulnerability Scale than Group 3. History of exposure to trauma or
      childhood abuse most clearly discriminated higher scores within the control
      sample. The findings highlighted the close relationship between histories of
      exposure to trauma and high scores on this scale. Additional analysis of these
      scores and those on the Glover Numbing Scale showed a close association between
      feelings of vulnerability and the numbing response.

PMID- 8559943
TI  - American Indian suicide rates and the economy.

PMID- 8559944
TI  - Televised violence: a Japanese, Spanish, and American comparison.
AB  - In Japan, Spain, and the USA during one week acts of violence (verbal and
      nonverbal) were rated on the Index of Television Violence by 3 raters in each
      country. In all three countries televised violence was more likely depicted in
      interpersonal conflict than against property. Fewer scenes of physical or fatal
      injury appeared in Japan than in the other two countries. Other observations were
      made. Replication is urged.

PMID- 8559945
TI  - Fluctuation of symptoms and social functioning in panic disorder with or without
      concomitant depression. A 5-year prospective follow-up.
AB  - After controlled treatment with either imipramine or doxepin with additional
      psychotherapy, 30 patients with pure panic disorder and 20 with concomitant
      depression were followed under ordinary treatment conditions over a 5-year
      period. While the overall level of illness severity was mild in both groups
      (slightly worse in the group with comorbidity), social impairment as well as
      fluctuation of symptoms were similar in both groups. Therefore, comorbidity of
      panic disorder and depression does not necessarily imply a poorer outcome in a
      self-referred patient sample initially treated with psychotropic drugs combined
      with supportive psychotherapy.

PMID- 8559946
TI  - Persistent cognitive defects after corrected hypothyroidism.
AB  - The authors present a case history in which cognitive defects caused by
      hypothyroidism persist after the patient has been rendered euthyroid.
      Concentration, recall and short-term memory appear to be most severely affected.
      The scarce literature on the subject is reviewed.

PMID- 8559947
TI  - 100 years of delusional parasitosis. Meta-analysis of 1,223 case reports.
AB  - Delusional parasitosis (DP) is mostly described in single cases or small samples.
      Data on epidemiology, nosological classification, therapy and course are
      therefore difficult to interpret. A thorough literature review is recommended to
      delineate common features of the syndrome. All case reports concerning DP (except
      toxic forms) were collected and analyzed according to a standardized protocol. DP
      is a disorder which may occur in every period of life but is much more frequent
      in older subjects. Sex differences with a predominance of females increase with
      age. Mean duration of delusion was 3.0 +/- 4.6 years (median: 1 year). Social
      isolation seems to be more a premorbid feature than a secondary phenomenon
      related to the delusion. Diagnostic classification revealed a high proportion of
      so-called 'pure' forms ('delusional disorders' in DSM-III-R or ICD-10) but the
      syndrome was also reported in schizophrenia, affective or organic psychosis or
      even as a neurotic symptom. Frequency of induced DP can be estimated between 5
      and 15%. Course of DP is not so unfavorable as commonly thought; in about half
      the patients a full remission was described during the observation period or at
      catamnesis. Short preclinical courses may indicate better outcome. Comparing the
      patients of the prepsychopharmacological era (before 1960) with those after, the
      rate of full remissions increased from 33.9 to 51.9%.

PMID- 8559948
TI  - The phenomenology of perceptual hallucinations in alcohol-induced delirium
      tremens.
AB  - In a qualified detoxication, states of anxiety caused by hallucinations can be
      specifically assimilated and psychologically reduced. Knowledge of the
      hallucinations experienced promotes the subsequent motivation phase. A
      semistandardized investigation of 64 patients with alcohol-induced delirium
      tremens was carried out over a period of 14 months in order to establish the
      nature of their perceptual hallucinations. Visual hallucinations predominated
      followed by auditory and tactile perceptual hallucinations. Amongst visual
      hallucinations pertaining to animals, the well-known 'white mice' were only
      reported once. Hallucinated cats, dogs, and snakes were most frequent, and were
      only then followed by mice (in general).

PMID- 8559949
TI  - The influence of comorbid disorders and of continuation light treatment on
      remission and recurrence in winter depression.
AB  - The objectives of this prospective study were to investigate the influence of
      comorbid disorders and that of continuation light treatment on remission rates
      and on a subsequent onset of a depressive episode in outpatients (n = 20) with
      winter depression. The effects of light treatment were evaluated by the
      structured clinical interviews and by the self-ratings of mood scored monthly for
      a follow-up period of 1 year. The remission rates of the patients (n = 8) who
      proceeded light treatment until the late winter were not significantly different
      from those of the patients (n = 6) who stopped treatment early during the winter.
      A more extensive variation in the rates during the year was observed in the
      former group of patients among whom the comorbid avoidant personality was more
      frequent, indicating an increased risk of an earlier onset of a depressive
      episode.

PMID- 8559950
TI  - Alexithymia and schizophrenias.
AB  - The purpose of this study is to verify whether an increasing degree of
      alexithymia correlates with a prevalence of negative over positive symptoms. The
      framework of the research is phenomenologically oriented conception of the
      illness-coping vulnerability paradigm. Schizophrenic basic symptoms as markers of
      schizotropic process activity were assessed with the Frankfurter Beschwerde
      Fragebogen, and cognitive features of the personological matrix were investigated
      using the Toronto Alexithymia Scale. Our findings on a sample of 20
      longitudinally followed outpatients advocate the hypothesis that among those
      factors characterizing the tendency towards the nonparanoid prototype of
      schizophrenia, impairment of language capacity and alexithymia may have a
      relevant role.

PMID- 8559951
TI  - Change in symptomatology of melancholic depression over two decades. Core
      symptoms and culturally determined symptoms.
AB  - The psychopathology of 183 patients with melancholic depression first admitted to
      our department in 1969 and 1970 was compared with that of 184 patients first
      admitted in 1989 and 1990. A multivariate statistical analysis was performed. The
      main results were as follows: A socioculturally invariable core syndrome of
      melancholia comprising psychomotor inhibition and vegetative disturbances can be
      identified. The contents of depressive thinking are, at least in part, culturally
      determined and vary with value changes in society. Paralleles to social change
      could be shown in particular for feelings of guilt and a concern with self
      realization.

PMID- 8559952
TI  - Family factors affecting bone marrow transplantation. A case report.
AB  - Bone marrow transplantation (BMT) is the last resort for children with leukemia
      for whom conventional treatments have failed. The case presented herein is one of
      an adolescent girl whose parents were unable to cope with the extreme challenge
      of BMT. Couple- and family-related data collected prior to the BMT showed this
      family was at risk. Indeed, throughout the ordeal the patient seriously regressed
      and her parents' reactions appeared to exacerbate her condition. At discharge,
      when left alone, the patient manifested somatic symptoms which required her
      parents to attend to her needs. How family factors may influence BMT outcome is
      discussed.

PMID- 8559953
TI  - Obsessive-compulsive disorder limited to pregnancy.
AB  - The relationship between obsessive-compulsive disorder and pregnancy is reviewed
      in the light of recent reports concerning the frequent onset and exacerbation of
      obsessive-compulsive disorder during pregnancy. We present the case of a young
      woman who developed obsessive-compulsive disorder during a pregnancy and
      recovered completely after delivery. Five years afterwards she is still symptom
      free. Several possible explanations for this unusual occurrence are discussed.

PMID- 8559955
TI  - Psychological aspects of non-cardiac chest pain.
AB  - Approximately 30% of patients visiting a cardiologist for the first time with
      complaints of chest pain appear to have normal coronary arteries. These patients
      generally have a higher prevalence of atypical chest pain, are relatively young,
      often female, in most cases suffer from panic disorder and have high scores on
      depression and anxiety scales. In this article some of the recent studies
      conducted in this particular line of research are reviewed and some possible
      explanations for the relationship between complaints and non-cardiac findings are
      presented. Furthermore, the ability of predicting non-cardiac chest pain from
      psychological factors and a range of follow-up studies are discussed. Finally the
      possibilities of treating cardiac phobia are mentioned.

PMID- 8559954
TI  - Holding on: depression, sensitization by antidepressant drugs, and the prodigal
      experts.

PMID- 8559956
TI  - To control or to be controlled? From health locus of control to morphine control
      during patient-controlled analgesia.
AB  - We postulated that patients with an internal locus of control, i.e. those who
      like to control their health problems themselves, would adapt more adequately to
      the 'patient-controlled analgesia' technique as compared to patients with an
      external health locus of control, who do not believe in their own control. Since
      contradicting studies have been published on this matter, we investigated
      relations between the demand for analgesics, perceived pain in the postoperative
      phase, and the health locus of control in the postoperative context of cardiac
      surgery. Findings demonstrate distinct utilization patterns between subjects with
      internal or external locus of control concerning total morphine consumption,
      number of unsatisfied demands and reduction of perceived pain.

PMID- 8559957
TI  - Family background and sexual abuse associated with somatization.
AB  - To help clarify the complex association between negative childhood experiences
      and somatization, the authors examined the possible relationship between self
      reported childhood sexual abuse, dysfunctional family background and several
      types of somatization in a nonclinical sample. Three anonymous questionnaires
      were completed by 202 female university students (average age 22 years). The
      findings confirm that severe or repeated childhood sexual victimization and a
      familial deficiency syndrome in childhood may be important in the pathogenesis of
      somatization.

PMID- 8559958
TI  - Medically unexplained somatic symptoms in different cultures. A preliminary
      report from phase I of the World Health Organization International Study of
      Somatoform Disorders.
AB  - The World Health Organization has recently launched an international study of
      somatoform disorders in different cultures. Five centres representing distinct
      cultures participated in phase I of the project, the main objective of which was
      to test the cross-cultural applicability and reliability of instruments for the
      assessment of somatoform disorders. The analysis of the assessed somatic symptoms
      showed that various aches and pains in different parts of the body represented
      cross-culturally the most frequent symptoms for which there was no medical
      explanation. Such symptoms may indicate the presence of an underlying mental
      disorder but can also represent a means for culture-specific expression of
      psychosocial distress. This bears particular significance for health
      professionals in primary and general medical care, who are most likely to
      encounter patients presenting with multiple, persistent and medically unexplained
      somatic symptoms.

PMID- 8559959
TI  - Psychological and somatic symptoms in young adults with chronic physical
      diseases.
AB  - To find out whether a long-term physical illness since childhood increases the
      risk of experiencing psychological and somatic symptoms, we interviewed a group
      of 487 patients aged 20-25 years and compared these findings to 211 controls.
      Both somatic (chi 2 = 9.11, d.f. = 6, p < 0.001) and psychological (chi 2 = 11.0,
      d.f. = 6, p < 0.001) symptom indexes varied significantly between the patient
      groups. Female sex, family conflicts during childhood, poor scholastic
      performance and depressive mental disorders were especially observed to be
      significant risk factors related to an excessive occurrence of these symptoms.
      The results suggest that a disabling disease lasting from childhood unit
      adulthood is complicated by a significant incidence of both psychological and
      somatic symptoms.

PMID- 8559960
TI  - How many HIV infections are there in Israel? Reconstructing HIV incidence from
      AIDS case reporting.
AB  - BACKGROUND: The reporting of AIDS cases to Israel's Ministry of Health is
      believed to be accurate, but the completeness of HIV surveillance is unknown. We
      implement a model that reconstructs HIV incidence in Israel from AIDS case
      reports excluding Ethiopian immigrants. METHODS: We apply the well-known method
      of backcalculation to AIDS cases reported to the Ministry of Health. The data are
      adjusted statistically to account for reporting delays and the elimination of
      AIDS Related Complex reporting. The analysis also accounts for the impact of
      differential administration of antiretroviral therapy to HIV-infected persons
      over time. RESULTS: Excluding Ethiopian immigrants, we find that the cumulative
      number of HIV infections reported to the Ministry of Health through December 1993
      (1,011) is not statistically different from the model's estimate of 922 (z =
      1.04; p = 0.30), though the reported number of new infections in recent years
      exceeds the modeleted rate. CONCLUSIONS: The low HIV incidence estimated among
      non-Ethiopian Israelis is consistent with other studies of sexually transmitted
      diseases and HIV-related risky behavior in Israel. This result counters the
      hypothesis that an explosive HIV epidemic will occur. That the number of recently
      reported new infections exceeds the estimate from the model could indicate that
      the reporting system is catching up with the extant spread of disease, or that
      the model is missing some aspect of the dynamics of HIV in Israel. We suggest
      that comparing future annual HIV incidence rates to the model's upper bound of 80
      infections per year will enable resolution of this issue over time.

PMID- 8559961
TI  - Physical activity within a community-based weight control program: program
      evaluation and predictors of success.
AB  - OBJECTIVES: To assess the feasibility and effectiveness of adding physical
      activity sessions to a weight control program in a community health center and to
      identify individuals suitable for outpatient group treatment with and without
      physical activity. METHODS: The study population included 42 overweight women who
      were randomly divided into treatment groups. Both treatment groups received
      guidance in nutrition and behavior modification and the exercise group also
      participated in physical activity sessions. Both treatments included 20 sessions
      and participants were followed up for eight months. RESULTS: In both treatments,
      significant improvements were seen in physical fitness, anthropometric
      measurements, nutritional knowledge, food consumption, and eating behaviors.
      Weight loss following three months of weekly sessions did not differ by treatment
      group. At follow-up there was a trend towards increased maintenance of weight
      loss in the exercise group, however differences were not statistically
      significant. Attrition rates were low in both treatments and participant
      satisfaction was high. Lower baseline BMI predicted larger weight losses, in
      particular in the exercise group. Other predictors of weight loss included poorer
      baseline eating behaviors and employment outside of the home. Perceived spouse
      support predicted continual participation.

PMID- 8559962
TI  - Obesity among Jewish and Bedouin secondary school students in the Negev, Israel.
AB  - BACKGROUND: Obesity, which is a common problem, may be associated with many
      pathological conditions. In this study we compare the prevalence of obesity among
      Jewish and Bedouin 11th and 12th grade students. METHODS: Five secondary schools
      were chosen in the Beer Sheva region. The health charts of school infirmaries of
      all 512 students attending high classes were reviewed. Birth weight, and weight
      at ages 6-7, 14-15, and 17-18 were abstracted together with height at 17-18 y, as
      these data were available to us. Triceps skinfold thickness measurements (TST)
      were made in a subsample of 243 students. Obesity was defined by comparing the
      individual weight and height (W-H) and the TST to standard norms for age and sex.
      RESULTS: The differences between the prevalence rates of obesity among Jewish and
      Bedouin students were not significant (13.7% vs. 11.0%; 9.9% vs. 6.2%, using the
      W-H and the TST methods, respectively). Obesity at the ages 6-7 and 14-15 is a
      significant risk factor for obesity at 17-18 y. (RR = 5.8 and 12.1 respectively
      with 95% CI = 4.0-12.7 and 7.0-21.9, respectively). No significant differences
      were found between the rates of obesity obtained by the W-H and the TST methods
      (13.3% vs. 8.6%).

PMID- 8559963
TI  - Patient delay in seeking help for potential breast cancer.
AB  - BACKGROUND: Patient delay in seeking medical attention could be a contributing
      cause in a substantial number of breast cancer deaths. The purpose of this study
      was to identify factors associated with long delay in order to identify specific
      groups in need of more intensive education regarding the signs of breast cancer
      and the importance of early treatment. METHODS: A study of 162 women with
      potential breast cancer symptoms was done in the area of Worcester, MA. Two
      methods of analysis were used. A case-control approach was used where the outcome
      variable was categorized into two groups of longer and shorter delay, and a
      survival analysis was used where the outcome variable was treated as a continuous
      variable. RESULTS: It was found that women with increasing symptoms were more
      likely to delay than women whose symptoms either decreased or remained the same.
      Women performing monthly breast self-examination and/or receiving at least bi
      annual mammograms were much less likely to delay than women who performed breast
      self-examination or received mammograms less often. It was also found that women
      using family practitioners were less likely to delay than women using other types
      of physicians. CONCLUSIONS: Patient delay continues to be a major problem in
      breast cancer, as 16% of the women here delayed at least two months before
      seeking help. This study presented a new and improved method for defining patient
      delay, which should be explored further in larger studies.

PMID- 8559964
TI  - The perceptual centre of a stimulus as the cue for synchronization to a
      metronome: evidence from asynchronies.
AB  - In tasks where subjects are required to tap in synchrony to a sequence of evenly
      spaced uniform auditory stimuli (a metronome), tap onsets typically tend to
      anticipate the metronome's stimulus onsets. We investigated this phenomenon,
      called "negative asynchrony", as a function of (1) the duration of the stimuli (1
      or 2, 50, 100, and 300 msec), (2) the rise time of the stimuli (0%, 40%, and 80%
      of stimulus duration), and (3) the interstimulus onset interval duration (500,
      700, and 900 msec). The results from three experiments with 28 different subjects
      showed a significant reduction of the negative asynchrony with longer stimulus
      durations, and the reduction was not significantly affected by the tempo of the
      stimulus sequence. Also, a prolongation of the rise time of the stimuli caused an
      analogous reduction of the negative asynchrony. Findings were taken to suggest
      that subjects use the perceptual centre rather than physical onset of stimulus as
      the cue with which to synchronize their responses to metronome stimuli. It is
      concluded that perceptual processes play an important role in synchronization.

PMID- 8559965
TI  - Diagnostic imaging and combined modality therapy of the cancer of the pancreatic
      head area.

PMID- 8559966
TI  - Carcinoma of the pancreatic head area. Epidemiology, natural history and clinical
      findings.

PMID- 8559967
TI  - Carcinoma of the pancreatic head area. Diagnostic imaging: ultrasound.
AB  - At present ultrasound (US) is performed as first choice exam in the diagnostic
      approach to the patient with suspected carcinoma of the pancreatic head area. The
      role of US is limited because of the difficult assessment of the infiltration of
      peripancreatic fat, of hollow viscera and of adjacent vascular structures. Lymph
      node invasion is better shown by CT than by US. A significant improvement in the
      diagnostic accuracy may be possible with the clinical application of the new US
      procedures as color-Doppler US, endoscopic US and laparoscopic US.

PMID- 8559968
TI  - Carcinoma of the pancreatic head area. Diagnostic imaging: computed tomography.
AB  - CT is at present considered the most accurate procedure in the staging of tumors
      of the pancreatic head area. Accuracy is based on a rigorous exam performed
      either with a conventional equipment or with spiral CT. Basic signs and symptoms
      and staging criteria according to TNM classification are analyzed. Comparison
      with other imaging methods is made based on a review of the literature. The role
      of a high resolution procedure is stressed especially in case of vascular
      infiltration, the determining factor to indicate resectability. In this respect
      CT is still to be considered the most reliable method.

PMID- 8559969
TI  - Carcinoma of the pancreatic head area. Diagnostic imaging. Direct
      cholangiography: ERCP.
AB  - In case of clinical and radiologic findings suggestive for periampullary cancer,
      primary goals of ERCP are the observation of the duodenum and the periampullary
      region and the opacification of biliopancreatic ducts to confirm the diagnosis of
      neoplastic stricture of biliopancreatic ducts and to establish its origin and
      extent at the level of the ducts and of the intestinal lumen. Secondarily, during
      ERCP, histologic and/or cytologic typing of the neoplasm by biopsy sampling and
      brushing of the lesion or exfoliative cytology of the bile and pancreatic juice,
      is feasible. At the level of the area of the pancreatic head various types of
      neoplasms can arise with different prognostic features which require different
      therapeutic approaches. Endoscopic cholangiopancreatography for its high
      sensitivity and specificity plays a major role in a correct combined
      radiodiagnostic imaging.

PMID- 8559970
TI  - Carcinoma of the pancreatic head area. Diagnostic imaging. Direct
      cholangiography: PTC.
AB  - The use of Chiba needle and a carefully performed procedure make percutaneous
      transhepatic cholangiography (PTC) highly diagnostic, with a low incidence of
      complications. However, because of their anatomy, visualization of pancreatic
      ducts, mandatory for an accurate diagnostic approach to the carcinomas of the
      pancreatic head area is impossible and thus this limits the diagnostic
      indications for PTC. At present it is performed in case of failure of endoscopic
      retrograde cholangiography (ERCP) or in view of interventional maneuvers. In
      carcinomas of the pancreatic head area PTC pattern is characterized by a more or
      less tight stenosis of the distal common bile duct with upward dilatation of
      biliary tree. The morphological features, the site and extent of stenosis usually
      permit a differential diagnosis between malignancies and benign forms
      (pancreatitis) while for definitive differentiation of cholangiocarcinoma from
      carcinoma of the pancreatic head infiltrating the common bile duct or from
      ampullary carcinoma, PTC should be combined with other imaging procedures.

PMID- 8559971
TI  - Carcinoma of the pancreatic head area. Diagnostic imaging: magnetic resonance
      imaging.
AB  - MRI using tailored pulse sequences and gadolinium administration on high field
      systems has a crucial role to play in the investigation of malignant disease of
      the pancreatic head. Breath hold spoiled gradient echo images after gadolinium
      administration in the capillary phase of enhancement and fat suppressed images
      are particularly effective MR techniques. This review highlights specific MRI
      findings in a spectrum of malignant tumors of the head of the pancreas. Emphasis
      is given to the ability of MRI to differentiate ductal adenocarcinomas from
      chronic pancreatitis and islet cell tumors. Improved detection and
      characterization of small, non organ deforming tumors and the recent
      implementation of MR cholangiography are also addressed.

PMID- 8559972
TI  - Carcinoma of the pancreatic head area. Therapy: resectability and surgical
      management of resectable tumors.
AB  - Surgical resection is being increasingly performed for carcinomas of the area of
      the head of the pancreas with curative intent. Pre-and intraoperative assessment
      of the site of origin and the stage of the lesion is of the utmost importance for
      a more favorable prognosis of non pancreatic forms and for a better evaluation of
      long term results of treatment adopted. Staging of non pancreatic periampullary
      tumors is usually very precise since they are most often shown to be resectable
      on laparotomy. Surgical resection by pancreaticoduodenectomy is the treatment of
      election based on good long term results. To the contrary, problems involved in
      the carcinoma of the head of the pancreas are non negligible. Some aspects
      related to the criteria of resectability of these tumors (diameter of primary
      lesion, infiltration of adjacent organs and large vessels, lymph node
      involvement) are discussed. How extensive pancreatic resection (subtotal, total
      or regional pancreatectomy) should be, is still a debated subject. In fact, it is
      not directly proportional to an improvement in prognosis. Complementary
      treatments directed to the improvement of the disappointing results at present
      achieved with surgery alone, are desirable.

PMID- 8559973
TI  - Carcinoma of the pancreatic head area. Therapy: intraoperative radiotherapy.
AB  - Pancreatic tumors represent a major field of application of intraoperative
      radiotherapy (IORT) with electron beams. First clinical studies were carried out
      principally on unresectable tumors and control of pain was observed in most of
      them. However, as for prognosis, IORT alone has yielded disappointing results.
      The use of IORT to boost external beam radiotherapy (ERT) frequently applied in
      recent trials, has improved local control but not survival rate because of the
      high incidence of abdominal metastasis. To-date, results of IORT used as an
      adjuvant to radical surgery have been controversial. As in unresectable tumors,
      studies have been focused on the combination IORT+ERT, however the
      intensification of the dose delivered to the tumor bed and the consequent better
      local control has not resulted in a better prognosis. A more significant
      contribution of IORT to the treatment of pancreatic tumors may come in the future
      from the combination of IORT with more effective methods in the control of the
      abdominal disease ("prophylactic" ERT to the liver or upper abdomen, intra
      arterial or intraperitoneal chemotherapy) or from variously timed combinations
      with ERT (neoadjuvant ERT+IORT).

PMID- 8559974
TI  - Carcinoma of the pancreatic head area. Therapy: nonoperative biliary drainage for
      palliation.
AB  - Jaundice is the dominant symptom in patients with biliary obstruction from
      carcinomas of the pancreatic head area. The many symptoms usually associated to
      prolonged biliary stasis (malnutrition, coagulopathy, pruritus hepatocellular
      failure, renal dysfunction, angiocolitis) is commonly resolved or relieved by
      biliary drainage. Palliation is frequently the only feasible treatment in these
      patients due to the biological aggressiveness of these tumors characterized by
      the early infiltration of adjacent tissues. Endoscopic and percutaneous
      procedures of biliary recanalization are as effective as those of surgical
      palliation, are more comfortable to the patients and burdened with a lower
      morbidity and mortality. In selected patients, palliation of jaundice can be
      combined with intraluminal radiotherapy or pancreatic drainage the latter aimed
      at the relief of the "obstructive" pain present in some patients with carcinoma
      of the area of the head of the pancreas.

PMID- 8559975
TI  - Carcinoma of the pancreatic head area. Therapy: intraluminal brachytherapy.
AB  - Intraluminal brachytherapy (Il-BRT) consists in the treatment of neoplasms by the
      positioning of radioactive sources in the lumen of cavitary organs such as the
      esophagus, the trachea, the bronchi and bile ducts. This procedure has been used
      to deliver relatively high doses of irradiation to bile duct and periampullary
      carcinomas while sparing the adjacent organs. Results of a number of reports
      appeared in the last fifteen years document the feasibility and tolerance of the
      procedure. Moreover these data seem to suggest that Il-BRT is able to prolong the
      survival of patients undergoing biliary drainage and that its use as boost dose
      in external beam radiotherapy (ERT) enhances the results of the latter. Combined
      ERT+Il-BRT is associated to an incidence of gastrointestinal ulcerations related
      to the total dose delivered. Better patient selection and standardization of
      reference dose represent prerequisites for testing this procedure in prospective
      randomized trials.

PMID- 8559976
TI  - Carcinoma of the pancreatic head area. Therapy: concomitant radiochemotherapy.
AB  - A series of studies carried out by the Gastrointestinal Tumor Study Group have
      shown the efficacy of the combination of external beam radiotherapy (ERT) and 5
      fluorouracil (5-FU) chemotherapy (CHEM) in unresectable and resectable tumors of
      the exocrine pancreas. In the former in particular, this method was shown to be
      superior to ERT alone as well as to polychemotherapy alone. In these studies 5-FU
      was administered during (concomitant chemotherapy: C-CHEM) or after ERT (adjuvant
      chemotherapy: A-CHEM). This led several authors to consider this combined
      treatment as reference standard for pancreatic carcinoma. Its prognosis is still
      definitely poor because of the difficult local eradication as well as because of
      the frequent early distant spread, especially at the abdominal level (hepatic and
      peritoneal). An improvement of present results may stem from the combination of
      ERT+C-CHEM +/- A-CHEM with methods of dose intensification at the local level
      (e.g. IORT) concurrently with the use of treatments aiming at a better control of
      the abdominal spread (e.g. ERT+C-CHEM for prophylaxis of the liver or upper
      abdomen).

PMID- 8559977
TI  - Carcinoma of the pancreatic head area: follow-up.
AB  - Preliminary results of a planned follow-up schedule based on periodic
      clinicoinstrumental controls applied to a population of 73 patients with
      pancreatic cancer undergoing combined modality treatments modulated according to
      the different prognosis, are reported. The following considerations are stressed:
      1) the feasibility of scheduled controls is confirmed by the low rate (1.4%) of
      patients lost to follow-up in spite of the rapidly fatal course of the disease,
      characterized by the deteriorating performance status in most patients; 2)
      radiologic exams should be performed in the same center where the patients were
      initially staged by a team experienced in the natural history of this disease and
      aware of the difficulties in assessing the treatment, surgery in particular; 3)
      supportive care plays a major role in patients followed-up for the frequent onset
      of symptoms which impact on the quality of life; 4) the interdisciplinary
      collaboration between surgeons, oncologists, radiotherapists, endoscopists and
      experts in nutrition and pain relief plays a major role.

PMID- 8559978
TI  - Policy goals for health and safety.
AB  - Health management and safety regulation are separate disciplines but share the
      aim to extend expectancy of life in good health. The need to improve cost
      effectiveness calls for their co-ordinated management according to a unified
      rationale. Three guiding principles of accountability, demonstrable net benefit
      and a uniform measure of performance, have been laid out in Canada by the Joint
      Committee on Health and Safety. They call for open accounting in terms of (health
      related quality-adjusted) life expectancy. The principles are utilitarian in
      format but, it is argued, inequity is naturally diminished in the process of
      optimizing cost-effectiveness through maximum marginal returns. Comments are made
      on practical implementation. The need for public consent in practice calls for
      two additional principles reflecting fair procedure and sovereignty of the
      citizens. It is concluded that public health and safety measures should be
      surveyed, documented for cost-effectiveness and prioritized for improvement.

PMID- 8559979
TI  - How dangerous is low level radiation?
AB  - Problems in the theoretical basis for the linear-no threshold theory of radiation
      carcinogenesis are reviewed, and it is shown that they very strongly suggest that
      the theory greatly overestimates the risk of low level radiation. A direct test
      of the theory, based on the radon-lung cancer relationship is described; it
      strongly reinforces that conclusion. However, it is shown that even if the linear
      no threshold theory is valid, the public's fear of low level radiation, at least
      in some contexts, is grossly exaggerated.

PMID- 8559980
TI  - Perspectives on cancer prevention.
AB  - Cancer prevention is a major component of cancer control, which also comprises
      screening, treatment, rehabilitation and palliative care. Preventive approaches
      need to be congruent with those adopted for other chronic diseases, with a major
      impact in reduction of incidence and mortality of many common cancers to be
      expected from smoking control and dietary modification. Increasing interest is
      now being paid to other environmental causes of cancer, and to gene-environment
      interactions. However, one of the major research needs remains the evaluation of
      better ways to convince people to make the necessary changes in their lifestyle
      that will reduce their risk of cancer.

PMID- 8559981
TI  - Canada's health status: a public health perspective.
AB  - Health status assessment and disease surveillance are essential to identify and
      priorize health issues, to evaluate intervention programs and to plan to meet
      future needs for health services. Canadians currently benefit by having among the
      highest life expectancies at birth in the world (81 for females, 74 for males).
      Disability-free life expectancies for females and males, respectively, were 10.1
      and 11.3 years lower for the lowest income quintile compared to the highest.
      Canada's infant mortality rate in 1990 (7/1000 live births) was one of the lowest
      in the world but within Canada, the rate in the lowest income quintile (10.5/1000
      live births) was almost double that in the highest income quintile (5.8/1000 live
      births). Fair or poor health was reported by 36% of adult Canadians in the lowest
      income category in 1990 compared to only 5% in the highest income group. The
      leading causes of premature death for females in 1991 were breast cancer,
      coronary heart disease, lung cancer, car crashes, birth defects and suicide;
      those for males were coronary heart disease, suicide, car crashes, lung cancer,
      birth defects, and AIDS. Lowest income quintile males had mortality rates at
      least double those for the highest income quintile for alcohol-related
      conditions, violence, injuries and emphysema. Cardiovascular diseases, cancer,
      musculoskeletal diseases, injuries and respiratory diseases imposed the highest
      direct and indirect economic costs in Canada in 1986. For all of these
      conditions, improved prevention is possible. For example, the forecasted tobacco
      related deaths before age 70 among current male smokers age 15 will far exceed
      those due to car crashes, suicide, murder, AIDS, and drug abuse combined.
      Population aging will aggravate trends for many chronic conditions especially
      those with increasing incidence rates; there will be large increases in the
      numbers of persons with aging-related cancers, dementias and other conditions.
      There is an urgent need for Canadian health jurisdictions to ensure that rational
      priorities, goals/objectives, strategies, and programs are in place to enhance
      prevention and disease control.

PMID- 8559982
TI  - Determination of a tolerable daily intake of DDT for consumers of DDT
      contaminated fish from the lower Yakima River, Washington.
AB  - DDT, DDE, and DDD have been detected at elevated concentrations in sediments and
      fish of the Yakima River, its tributaries and drainages. An assessment was
      conducted to evaluate the public health significance of eating fish from the
      river. This was accomplished by establishing a daily intake level of DDT for the
      population of greatest concern, and comparing this level to a tolerable daily
      intake. The most sensitive and highly exposed group was determined to be
      breastfeeding infants. Infant daily intakes of DDT, based on estimated mother's
      DDT-breast milk levels, were compared to a recommended tolerable daily intake.
      Results indicate that mothers who frequently consume Yakima River bottom-feeding
      fish could have breast milk DDT concentrations sufficiently high to expose their
      infants to levels above the tolerable daily intake.

PMID- 8559983
TI  - Perception and acceptance of technological and environmental risks: why are poor
      countries less concerned?
AB  - The research has been aimed at answering two questions: (1) What factors impact
      perception and acceptance of technological and environmental hazards? (2) Why are
      rich societies involved more in protecting their environment and health than poor
      societies? Data has been collected from representative samples of two countries-
      Poland and Sweden. The results indicate that (1) contrary to earlier findings,
      the inverse relations between perceived benefits and dangers of hazards has not
      been observed, (2) acceptance of a risk has been mostly influenced by perceived
      benefits, (3) rejection of a risk has been mostly influenced by its perceived
      harmful consequences. Concerning the second question, it has been found that: (1)
      perceived hazard's danger and benefit is not the only factor that impacts its
      acceptance, and (2) a broader economic context can impact acceptance (tolerance)
      of hazards. It has been found that being aware of high dangers and not very high
      benefits of hazardous activities, Poles still have accepted them. Thus, Poles
      seem to follow an old proverb: "When one does not have what one likes, one has to
      like what one has."

PMID- 8559984
TI  - [Absent or reverse diastolic umbilical flow].
AB  - We show our experience in the diagnostic and management of 19 pregnancies with
      absent or reverse diastolic blood flow velocity (ARFV) in the umbilical artery.
      The presence of ARFV was a rare condition (2.2% of the high risk patients), and
      it was associated with a poor prognosis shown by the high percentage of fetuses
      SGD (small for gestational age) (63.2%), malformations and hydrops fetalis (26%)
      and asphyxiated fetuses, giving a final perinatal mortality rate of 36.8%. In 8
      cases (42.1%) the termination or pregnancy was delayed for at least 48 hours,
      allowing in some cases the administration of corticosteroid. There were
      significant differences when comparing the groups of survivors and non survivors
      in relation to the gestational age at the moment of delivery (33.1 +/- 3.4 vs
      28.6 +/- 3.8 weeks), malformations (8.3 vs 57.1%) and C-section (91.7 vs 42.9%).
      Finally, we conclude that the presence of ARFV in the umbilical artery is
      associated with a critical fetal condition and termination of pregnancy should be
      considered. In this decision the gestational age and fetal and maternal well
      being ought to be taken into account when choosing the best moment and route of
      delivery.

PMID- 8559985
TI  - [Randomized comparative study of induced labor with oxytocin and misoprostol in
      prolonged pregnancies].
AB  - The efficacy of oxytocin for induction of labor at 41 to 42 weeks of gestational
      age, was compared with misoprostol (a PGE1 analog) in 100 pregnant women. Half a
      tablet containing 100 mcg of misoprostol was placed intravaginally in 50 women
      and the remaining 50 received iv oxytocin (2-32 mU/min). The obstetric features
      were similar in both groups. Delivery within 24 hours was achieved in 88% of the
      patients induced with misoprostol and in 72% with oxytocin (p < 0.05). The mean
      time from induction to delivery was similar, 10.3-10.9 hrs (p NS) and no
      differences in obstetric and perinatal outcomes were found. Polisystoly with
      misoprostol, was the only side effect observed in the study (11.4%), and was
      without neonatal consequences. CONCLUSION: intravaginal misoprostol (100 mcg), is
      more effective, cheaper and less stressful than IVI oxytocin in post term
      inductions. The safety profiles of both were similar.

PMID- 8559986
TI  - [Fetal endoscopic surgery in a case of twin pregnancy complicated by reversed
      arterial perfusion sequence (TRAP sequence)].
AB  - We present the first report in our country of endoscopic fetal surgery in a
      patient with a twin pregnancy and twin reversal arteral perfusion (TRAP
      sequence). We performed fetoscopic ligation of the umbilical cord of an acardiac
      twin at 26 week's gestation.

PMID- 8559987
TI  - [Leukemia and pregnancy. Review apropos of a clinical case].
AB  - A clinical case is presented of a 37 year old patient with acute myelocytic
      leukemia who conceived while in therapy. The pregnancy was controlled in our
      department in association with the Hematology Department. A cesarean section was
      performed in the 37th week of gestation, resulting in a healthy newborn. A review
      of literature is presented, analyzing the association between these two
      conditions, as well as repercussion on the mother and infant and the recommended
      obstetric management.

PMID- 8559988
TI  - [Pustular psoriasis in pregnancy].

PMID- 8559989
TI  - [Cervical cystic hygroma].
AB  - We present a clinical case of prenatal ultrasound diagnosis of cystic hygroma
      resulting in intrauterine fetal death. In the follow up we review the clinical
      pathology of the case.

PMID- 8559990
TI  - [Pulmonary hypoplasia of the newborn infant in a pregnancy complicated with
      ovular premature rupture and oligohydramnios].
AB  - Premature amnion rupture occurs in about 5%-7% of normal pregnancies. Early and
      prolonged decreased amount of amniotic fluid determines deformities and
      impairment of fetal lung development. We report a case of a 35 year old mother
      with severe oligohydramnios since 25 weeks gestation, secondary to premature
      rupture of membranes. A male baby was born a 31 weeks with unmanageable asphyxia
      dying eleven hours later. Pathologic findings revealed a Potter phenotype
      including severe lung hypoplasia. The fall in intrauterine volume affects,
      through diverse mechanisms lung growth and maturation. The duration and severity
      of oligohydramnios are important elements in predicting the risk of pulmonary
      hypoplasia and neonatal morbidity.

PMID- 8559991
TI  - [Bacterial vaginosis II. Related pathology and therapy].

PMID- 8559992
TI  - [Family counseling in infertility couples].
AB  - For couples who want to have children, infertility is an undesirable situation.
      Certain emotions both obvious and hidden can emerge which could complicate the
      clinical picture and the couple's relationship. Fifteen infertile women between
      the ages of twenty five and forty were interviewed and invited to form workshops
      to identify the emotions evoked by infertility. The spontaneous expressed
      emotions were; fear, anxiety, frustration loneliness and sadness. The non
      expressed emotions were; rage and guilt. Women held themselves more responsible
      for the couple's infertility and generally protected their partners even when
      male factors were the evident cause. Men showed scant interest iin joining
      infertility workshops. Family orientated advice is vital in the management of the
      infertile couple both in the diagnosis and treatment.

PMID- 8559993
TI  - [Development of a human semen bank].

PMID- 8559995
TI  - [Experience with bladder-amniotic shunts].
AB  - Four bladder-amniotic shunts were done in three fetuses with megacystis. The
      procedure was successful in all cases on the first attempt. The interval between
      the shunt insertion and delivery was range from three to twenty eight days.
      Pulmonary and renal damage were irreversible in two fetuses. Spontaneous abortion
      occurred with the third fetus which had multiple malformations. We believe that
      selection of candidates for such procedures should be improved. Early diagnosis
      and referral to high technology centers will increase clinical experience.

PMID- 8559994
TI  - [Parasitic and viral marker detection in pregnant adolescents and their newborn
      infants at risk].
AB  - We have investigated the prevalence of antibodies against Toxoplasma gondii,
      Trypanosoma cruzzi, Hepatitis B virus, cytomegalovirus, rubella virus, and human
      immunodeficiency virus in 139 adolescent pregnant women and in their high risk
      newborn children. The methods employed were the Sabin and Feldman reaction,
      complement fixation reaction, ELISA, and xenodiagnostic 30.9% of the pregnant
      group were seropositive for T. gondii, both mothers and newborns were IgM
      negative. Two mothers (1.4%) presented anti T. cruzii antibodies, and one newborn
      child had circulating parasites. Related to the virological studies, 93.5% of the
      population were anti CMV antibodies positive and all their newborns were IgM (-)
      90.6% of the adolescents were rubella positive and one was seropositive to VIH.
      We conclude that the prevalence found in this group of adolescent pregnant women
      are not significantly different to the one reported for the general pregnant
      women population.

PMID- 8559996
TI  - [Experience with Wertheim-Meigs surgery at the Dr. Juan Noe de Arica Hospital].

PMID- 8559997
TI  - [Postoperative low patella. Treatment by lengthening of the patellar tendon].
AB  - PURPOSE OF THE STUDY: Patella infera is a post operative complication that can be
      prevented in most cases. This study was undertaken to determine etiological
      factors and to determine the means to avoid patella infera following knee
      surgery. The authors describe a new surgical technic to correct this complication
      and describe prognostic factors for achieving good results. MATERIAL AND METHODS:
      From 1985 to 1991, 35 patellar tendon lengthenings were performed in 35 patients.
      There were 28 female and 7 male patients with an average age of 37 years (21 to
      72). Follow-up averaged 27 months and all patients had radiographic follow-ups.
      All patients had previous knee surgery: 21 for patellar pain (= patellar pain), 9
      ACL reconstructions, 5 traumatic lesions. The range of motion of the knee was
      between 5 and 120 degrees. Patients complained of a burning pain in the patellar
      region and the sensation that the knee was held in a vice. The average Insall
      index was 0.55 (0.3 to 0.87). 25 patients had osteoporosis of the patella and 31
      patients had a typical "sunrise" aspect on axial radiographs in 30 degrees of
      flexion. The usual diagnosis was that of algodystrophy. All patients underwent
      patellar tendon lengthening. RESULTS: Intra operative findings showed transverse
      retractions leading to resection of the medial and lateral retinaculum. The
      patellar tendon was short but its histological structure was normal. 15 patients
      had excellent results with no residual pain and were able to resume sports
      activities. 11 had good results with residual pain in hyperflexion and 9 had poor
      functional results, however nocturnal pain disappeared. Range of motion was
      between 0 and 130 degrees. Radiographic results were excellent since the
      preoperative average Insall score of 0.55 increased to 1.02 at follow-up.
      DISCUSSION: Patella infera is caused by combination of two factors: patellar
      surgery (painful patellar syndrome, patellar instability, ACL reconstruction
      using the mid third of the patellar tendon) and painful post operative
      rehabilitation with no active quadriceps contractions. To avoid this
      complication, the knee should be braced in 20 degrees of flexion to tense the
      patellar tendon and rehabilitation should be undertaken with active quadriceps
      contractions. Patellar lengthening is a successful procedure with the results
      being dependent upon number of previous surgeries, cartilage damage and, most
      importantly, the patellar index: between 0.8 and 0.65 the results are uncertain,
      < 0.6, the results are usually good. CONCLUSION: Patella infera is not a frequent
      complication of knee surgery. It is important to diagnose it early in order to
      prevent it. For chronic cases, surgical criteria should be strict: sensation of
      burning pain, lack of motion, unstable flexed monopodal stance, "sunrise" aspect
      on axial radiographs and a patellar index < 0.6. Patella infera differs from
      algodystrophy and re operation by retinacular release is indicated if the delay
      from previous surgery is < 2 months. In older cases, patellar tendon lengthening
      should be undertaken.

PMID- 8559998
TI  - [Surgical treatment of cervical disk displacement. Anterior or posterior
      approach?].
AB  - PURPOSE OF THE STUDY: This study is a retrospective analysis of the treatment of
      cervical soft disc herniation comparing anterior and posterior approach. MATERIAL
      AND METHODS: Twenty eight patients presenting with cervico-brachial radiculopathy
      secondary to acute soft posterolateral disc herniation were reviewed. Cases with
      myelopathy or radiculopathy secondary to chronic spondylosis were excluded.
      Involved level was C5-C6 or C6-C7 in most cases. There were 14 females and 14
      males. Age at operation averaged 44 years. Fourteen patients underwent an
      anterior approach with discectomy and fusion using autologous iliac bone graft.
      Average age was 46 years in this group with an average follow-up of 30 months.
      Average duration of surgery was 2 hours. Average hospital stay was 6 days.
      Fourteen patients underwent a posterior approach with partial lateral laminotomy
      extending medially for several millimeters over the facet joint. Extruded disc
      material was removed in 10 cases. No curettage was performed. Average age at
      surgery was 41 years with an average follow-up of 36 months in this group.
      Average duration of surgery was 70 minutes. Average hospital stay was 6 days.
      RESULTS: Patients were evaluated 3 months post-operatively and at their maximum
      follow-up. At 3 months follow-up, no patient complained of radicular pain;
      occasional cervical pain was present in 5 cases following posterior surgery but
      was not observed at late follow-up. Return to work was possible on an average of
      3 months in both series. Results were graded as excellent, good, fair and poor.
      At late follow-up, in patients with a posterior approach, there were 8 excellent
      results, 5 good results with neck fatigue at work, and 1 fair result requiring
      analgesics. In patients with an anterior approach, there were 7 excellent
      results, 6 good results, and 1 fair result. Two patients complained of pain at
      the iliac donor site. DISCUSSION: These results suggest that the anterior
      approach gives better short term results, but no significant difference is
      observed between anterior and posterior approaches a few years after surgery.
      Although the anterior approach is more appropriate than the posterior one for the
      treatment of central disc herniation, the posterior approach may be considered as
      an alternative to anterior discectomy and fusion for antero-lateral soft disc
      herniation.

PMID- 8559999
TI  - [Hip dysplasia in adolescence].
AB  - INTRODUCTION: Hip growth continues on till adolescence with the fusion of the
      different ossification centers. Does this growth exist in hip dysplasia? What is
      the role of surgery at adolescence? Is an additional varus osteotomy indicated
      with a pelvic osteotomy? MATERIAL AND METHODS: Clinical and radiological criteria
      of adolescent hip dysplasia were studied in a series of 18 patients (mean age 12
      years). The 28 hips were divided into 4 groups depending on the treatment: non
      operated hips (group 1, N = 8), hips operated on only by pelvic osteotomy (group
      2, N = 8), hips operated on by combined pelvic and femoral osteotomies (group 3,
      N = 9), and hips operated on only by femoral osteotomy (group 4, N = 3). Tonnis's
      clinical criteria were used. The acetabular index of the weight bearing zone, the
      center-edge angle of Wiberg, the acetabular angle of Idelberger and Frank, the
      neck-shaft angle, the head coverage index were measured and compared between the
      4 groups (average follow-up was 46 months). RESULTS: We noted continuation of
      growth of the acetabulum at adolescence with a correction of moderate hip
      dysplasia when the head was covered (group 1), the acetabular index of the weight
      bearing zone decreased from 20.1 degrees to 11.1 degrees; the center-edge angle
      of Wiberg increased from 15.25 degrees to 23 degrees. The comparison of groups 2
      and 3 showed that an additional femoral osteotomy does not change significantly
      the radiologic results. DISCUSSION: Does surgery benefit at adolescence from the
      growth which exists during this period? The clinical results and the evolution of
      arthrosis following a Chiari pelvic osteotomy are better when the operation is
      performed early. CONCLUSION: A pelvic osteotomy is indicated in symptomatic hips,
      when the congruity is abnormal, with deficient head coverage, as well as moderate
      dysplasia when the evolution of the acetabular parameters are not satisfactory. A
      femoral osteotomy in addition to a pelvic osteotomy does not seem justified.

PMID- 8560000
TI  - [Value of pelvic osteotomy in the management of the hip in children with cerebral
      palsy].
AB  - PURPOSE OF THE STUDY: The authors analyzed the effectiveness of pelvic osteotomy
      for the treatment of hip dislocation or subluxation in CP children. MATERIAL:
      Fifteen pelvic osteotomies were performed on 11 children aged 30 months to 12
      years (mean age 6 years). Seven children suffered from Little's disease. Follow
      up averaged 10 years (from 2 to 16). Six children were reviewed at the end of
      growth (9 cases). METHODS: A Salter or triple osteotomy with adductor release was
      performed. Four cases had also a proximal femoral osteotomy. RESULTS: Following
      surgery, the mean Reimers' percentage decreased from 55 to 0 per cent. Correction
      was perfect in 11 cases, incomplete in 4 but excentration remained under 20 per
      cent. At the end of growth, 6 out of 9 hips remained stable without any further
      surgery, 2 hips developed slight excentration (less than 20 per cent) and one
      recurrent subluxation was treated by proximal femoral osteotomy. Six hips
      remained stable but their growth was not ended at last review. DISCUSSION: This
      surgical procedure is compared to others described in literature. Pelvic
      osteotomy with tenotomy improves acetabular cover and corrects muscle imbalance.
      Its risks seem overestimated in the literature. Both pelvic and femoral
      osteotomies are useful in specific cases. CONCLUSION: Triple or Salter osteotomy
      with adducter release seems to be a useful procedure to restore good hip
      morphology at the end of growth. No posterior dislocations following this
      osteotomy were seen in spite of the important correction. Proximal femoral
      osteotomy is not always necessary.

PMID- 8560001
TI  - [Treatment of osteoid osteoma by CT-controlled percutaneous drill resection.
      Apropos of 27 cases].
AB  - PURPOSE OF THE STUDY: Osteoid osteoma is a benign tumor requiring excision due to
      pain, usually severe and invalidating. Surgical "en bloc" resection is not always
      easy. Complete resection of the nidus is required to prevent recurrence while at
      the same time a limited resection should also be used to avoid a pathological
      fracture or a growth plate injury in children. In order to achieve these 2 goals,
      we have developed an alternative method: CT guided drill resection. This method
      is reported with special reference to its technical aspects. MATERIAL AND
      METHODS: Twenty seven patients (16 children and 11 young adults) were treated
      during a seven year period (June 87 through June 94) and observed clinically and
      radiologically with an average two-year follow-up (range one to three years).
      Osteoid osteoma was localized mainly in the lower limb: Femoral neck (or head):
      10 cases, 3 in the acetabulum; Femoral shaft: 6 cases; Tibial shaft: 4 cases.
      Diagnosis was based on clinical features and imaging: radioisotope bone scan and
      computed tomography in all cases--angiography in 3 patients to assess the
      diagnosis more accurately. The procedure was performed under general anesthesia
      (a short hospitalization is needed). The nidus was first localized by Computed
      Tomography, then approached and resected through a small percutaneous incision. A
      special device has been manufactured in order to remove a bone cylinder
      containing the nidus. It was thus possible to perform histological studies of the
      specimen and confirm the diagnosis. Histological confirmation was possible in 50
      per cent of the cases. No complication (except a case of transient extensor
      hallucis palsy) was observed in this series, 24 patients healed completely; pain
      disappeared immediately, and the control CT scan returned to normal after a one
      year follow-up. In 3 patients, because of a technical error, the nidus was not
      totally removed. These patients underwent a second procedure, which was
      effective. DISCUSSION: This method is a good alternative to the direct surgical
      approach because of its technical advantages: precision in nidus localization and
      minimal bone resection; consequently, one should underline the practical benefits
      for the patient: short hospitalization, immediate full weight bearing, quick
      return to socio-economic activities. Furthermore, some localizations of the nidus
      which are difficult to reach (for instance the acetabulum) represent a good
      indication for the method. Accurate pre-operative diagnosis has now become
      possible with recent advances in imaging techniques but still remains
      "uncertain". The resection of the specimen allows confirmation of the diagnosis
      is most of cases. This procedure should ideally be performed by a team
      (orthopedic surgeon and a radiologist): collaboration instead of competition is
      in fact the best way to progress in this field of "interventionnal radiology".

PMID- 8560002
TI  - [Dual-energy X-ray absorptiometry: value in orthopedics].
AB  - We emphasize the opportunity of an in vivo bone mass measurement with an easy and
      accurate technique for orthopedic practice. At the present time, Dual Energy X
      Ray Absorptiometry (DEXA) is the most used technique, and is a safe and short
      examination. It can assess the quantity of mineral of any region of the body with
      a remarkable reproducibility (1 to 3 per cent). New machines are improved, and
      they permit many practical applications beyond the osteoporosis field. Thus, in
      orthopedics, we can distinguish several interesting topics. Peripheral risk of
      fracture can be evaluated because of good correlation between bone mineral
      content and biomechanical properties of bone. Even if a peripheral fracture
      occurs after a fall, low bone mineral density plays an important role, as in the
      case of femoral neck fractures in elderly patients. In traumatological practice,
      a DEXA with a specialized advice has to be requested if the traumatism cannot
      fully explain the occurrence of the peripheral fracture. Low bone mineral density
      defines an osteoporotic state, with the possibility of selecting adequate
      therapy. The good reproducibility of the measurement allows early estimation of
      bone loss following a period of immobilization. Varying models of osteosynthesis
      can be compared in vivo, to evaluate a decrease of "stress shielding" bone
      resorption. The role of stiffness of an implant on regional bone mineral content
      can be assessed. Likewise, periprosthetic bone mineral content can be measured in
      various regions, and followed over time. Specific software allows the exclusion
      of the region where the metallic prosthesis is projected. The reproducibility of
      this peripheral bone mineral content is 2 to 3 per cent, which individually
      allows an estimation of variations of more than 5 per cent. It will be possible
      to evaluate in vivo the influence of various parameters of the prosthesis on bone
      mineral content in controlled studies, such as the role of the shape, the
      position, the structure, the coating. Mineral content of biomaterials and bone
      grafts are taken into account. Focusing the X Ray beam allows ultrahigh
      resolution. Precise measurements of very small parts of bone such as rodent tibia
      or vertebra are possible. The good reproducibility (2 per cent) authorizes the
      evaluation of various parameters which modify bone remodeling, such as
      immobilization or activity, ovariectomy. Preventive or curative therapeutics
      which change bone mass can be evaluated in animal pre clinical studies. There are
      other methods of measurement of bone mineral content. Digitalization of
      radiographs is not sufficiently accurate and CT Scan generate high levels of
      radiation. The DEXA is actually the best compromise for an accurate and
      reproducible measurement of the bone mineral content in vivo. This method will
      certainly be an important tool in orthopedics for several clinical or animal
      investigations in the future.

PMID- 8560003
TI  - [Adamantinoma and osteofibrous dysplasia of the tibia].
AB  - PURPOSE OF THE STUDY: Fibrous dysplasia and adamantinoma of the long bones are
      two different entities encountered on the same part of the tibial shaft. The
      relationship between these two diseases seems to be established. We describe a
      case with some common, features arguing for a single pathology. MATERIAL AND
      METHODS: A seven year old boy presented in 1974 with a destructive lesion
      involving the cortex of the tibial shaft. The patient subsequently presented
      several fractures, treated surgically and has been followed for nineteen and a
      half years. The first biopsy specimen in 1974 led to the diagnosis of ossifying
      fibroma or fibrous dysplasia. It was reviewed with immunohistochemical technics
      but no epithelial component could be found. RESULTS AND DISCUSSION: These
      pathologic aspects led to the diagnosis of adamantinoma associated with
      osteofibrous dysplasia of the tibia. Twenty five such cases were found in the
      literature. Two theories are proposed: 1) these two diseases are independent and
      coexist on the same bone; 2) there is only one disease with different features
      that are either those of fibrous dysplasia or those of adamantinoma.
      Immunohistochemical technics are needed for diagnosis. CONCLUSION: Two sorts of
      adamantinoma can be observed on the long bones: adamantinoma without features of
      fibrous dysplasia with poor prognosis, adamantinoma with fibrous dysplasia's
      features called "differentiated adamantinoma" with a better prognosis.

PMID- 8560005
TI  - [Tuberculosis of the greater trochanter. Apropos of 2 cases].
AB  - INTRODUCTION: The authors report two cases of tuberculosis of the greater
      trochanter as an uncommon localization in osseous tuberculosis. MATERIAL AND
      METHODS: 1st case: A 77 year old male presented with hip pain and swelling.
      Laboratory studies revealed an increased erythrocyte sedimentation rate. The
      patient had a positive skin test reaction for tuberculosis. Radiographs showed
      greater trochanter remodeling. M.R.I. demonstrated a bilobed abscess. There were
      enough arguments to initiate medical treatment, before surgery: excision of the
      abscess and partial trochanteric resection. 2nd case: In a 51 year old male, a
      large lytic lesion of the whole greater trochanter suggesting benign bone tumors
      was found an radiographs after a traumatism. Curettage and grafting were
      undertaken. The final diagnosis was made with the results of the intra-operative
      samples culture of and led to appropriate medical treatment. RESULTS: The outcome
      was good in both cases with four years follow-up for the first case, and two
      years for the second one. DISCUSSION: Trochanteritis Tuberculosis occurs in 1.8
      per cent of bony tuberculosis cases. Local symptoms are discrete and the
      diagnosis is belatedly made when the tuberculous abscess appears. Radiographs and
      CT scan show the bony lesions: unevenness of the contours of the trochanter and
      several gaps in it. MRI shows the abscess and its spread. The microbiological
      test (when antibiotic therapy has not been initiated) and anatomo-pathological
      tests confirm the diagnosis. General treatment is based on a six month long
      specific antibiotic therapy. Local treatment concerns the abscess and the bony
      lesions. As the case may be; careful curettage is undertaken, or wide excision is
      performed.

PMID- 8560004
TI  - [Bone metastasis of leiomyosarcoma. Apropos of a case].
AB  - INTRODUCTION: Bone leiomyosarcoma is a rare tumor, whether it may be primary or
      secondary. The authors report on the case of a woman, aged 67, admitted in
      January 1992 complaining of pain in the left hip and the upper end of the femur.
      CASE REPORT: In 1985 the patient underwent surgical excision of a soft tissue
      tumor in the right thigh, histologically diagnosed as a benign fibrous tumor.
      This lesion recurred locally four times and repeated excisions were performed
      throughout the years, always with a histological diagnosis of a benign lesion. On
      admission to hospital, the physical examination as well as laboratory data and
      plain roentgenograms were unremarkable. Both tomography and MRI showed a lesion
      in the upper end of the left femur. An isotopic bone scan showed marked increased
      uptake in the left hip extending to the femoral diaphysis. An open biopsy was
      performed for histology, immunohistochemistry and electron microscopy. A
      diagnosis of metastatic leiomyosarcoma was made. The retrospective histological
      examination of specimens of the soft tissue tumor excised in 1985 showed the same
      immunohistochemical features of the contralateral leiomyosarcoma. On this basis,
      one stage resection of the left hip and the upper end of the femur was performed
      and a Kotz modular prosthesis was inserted. Postoperative healing was achieved
      without any complications and the function of the operated limb was satisfactory.
      Three months after the operation pulmonary lesions were noted on chest
      radiographs and CT scan. The patient died two years after the first admission for
      widespread metastasis. DISCUSSION: In the reported case, the bony metastasis
      appeared to be the presenting finding of the soft tissue tumor of the
      contralateral thigh. This presentation is rare in previously published series.
      The misdiagnosis of the primary tumor had caused local recurrences, and an
      increased malignity occurred. According to the literature, a soft tissue
      leiomyosarcoma can be easily confused with other spindle cell lesions. Therefore
      an accurate histological and ultrastructural diagnosis is necessary for adequate
      surgical treatment.

PMID- 8560006
TI  - [10 years follow-up of the M.E. Muller self-locking cemented total hip
      prosthesis].
AB  - PURPOSE OF THE STUDY: This study concerns the analysis 10 years follow-up
      survival, of the Muller self-locking cemented straight stem, inserted with a
      cemented polyethylene socket. MATERIAL: 193 Muller self-locking cemented straight
      stems were inserted by the author between january 82 and March 83. The first part
      of the study is a survival analysis of the individual components. The second part
      is a clinical and a radiological evaluation of 93 hips reviewed at 10 to 11 years
      with the initial components. RESULTS: Using revision of the components as the
      definition of failure, survival analysis depicted 94.3 per cent survival for the
      socket (86.5 per cent), and 98.3 per cent for the femur (95 per cent). 7 sockets
      and 2 stems were revised in 7 patients (one of them is a late infection at 9
      years). Up to date this revisions have been successful. 93 patients, 50 females
      et 43 males, were reviewed, at an average follow-up time of 10.5 years, with the
      initial components. 70 hips were rated excellent, 12 good, 9 fair and 2 poor. The
      two poor results presented stiff joints at follow-up. Complete radiographic
      studies were available for these 93 patients. 38 sockets had no bone-cement radio
      lucent lines, 52 had limited non progressive radiolucent lines, 3 had a
      circumferential radiolucent zone around the cup; two of them migrated. The mean
      polyethylene wear was 1.30 mm (0.4-2.6). On the femur, there was a low incidence
      of radiolucencies: 9 patients had limited radiolucencies on the AP view, 4 on the
      lateral view, with no stem settling more than 3 mm. Demarcations occurred
      predominantly in Gruen zones 5 et 6 with undersized stems placed in valgus. 13
      per cent of the femurs presented some degrees of osteolysis with internal defects
      of the medial cortex, one was extensive. DISCUSSION: The clinical result of the
      stem was satisfactory but roentgenographic evaluation revealed signs of
      osteolysis in 13 per cent of the femurs. This mechanism of bone loss has been
      clearly documented to occur because of accumulated polyethylene wear debris, a
      factor which also accounts for the high failure rate of the socket. It could be
      related to the high friction produced by the 32 mm metallic head. Migration of
      the debris along the medial cortex is probably consecutive to the design of the
      self locking stem with a lack of cement on the borders. CONCLUSION: The
      satisfactory long-term results of the cemented straight Muller stem encourage us
      to continue, but the 32 mm metallic head should be abandoned. We prefer the use
      of a 32 mm alumina ceramic femoral head combined with the same stem and
      polyethylene acetabular cup. The study of this next series with the same follow
      up is currently being evaluated.

PMID- 8560007
TI  - [Bousquet's device in the treatment of recurrent dislocation of a total hip
      prosthesis. Apropos of 13 cases].
AB  - PURPOSE OF THE STUDY: Dislocation following total hip arthroplasty (THA)
      continues to be a problem. An innovative treatment is described with the
      intermediate Bousquet's prosthesis. This study reported 13 cases and demonstrates
      its high reliability despite the origins of the dislocation. Recurrent
      dislocation following initial dislocation, occurs in between 25 to 60 per cent of
      the cases reported in the literature. The main cause is a malpositioned
      prosthetic component and especially a retroverted acetabulum. The other reasons
      for dislocation were: trochanteric non-union, bone or cement impingement,
      previous surgery, age and neurologic disorder. In every case the instability of
      the hip may be caused or increased by muscular insufficiency. Various methods are
      described to control recurrent dislocation: repositioning the component,
      posterior acetabular wall component, trochanteric advancement, retentive
      acetabular component, bracing. When the cause is clear and isolated, the rate of
      success may be 70-80 per cent. This study examines the results of a revision
      procedure with the intermediate Bousquet's prosthesis. MATERIAL AND METHODS: 13
      recurrent dislocations were treated with the intermediate Bousquet's prosthesis.
      There were 10 women and 3 men with an average age at operation of 73 years. The
      main cause in 7 cases was an abductor insufficiency including 4 trochanteric non
      unions. The other causes were 6 component malpositions, 7 previous surgery, 1
      impingement. The average delay between the first dislocation and revision was one
      year. The Bousquet's acetabular component is an steel cup covered with alumina,
      impacted without cement. The polyethylene component is free in the cup and
      retentive on the femoral head. The femoral positioning was not modified. RESULTS:
      The revision did not correct all of the causes of luxation, however we noted only
      one case of dislocation and no recurrent dislocations. DISCUSSION: At last follow
      up, all recurrent dislocations were controlled. Nevertheless, there remained 7
      abductor insufficiencies and 4 femoral malpositionings. In the literature the
      rate of success depends on the cause. The main difficulty is the treatment of
      joint laxity. Some authors propose trochanteric advancement, a larger head, a
      posterior wall acetabular component, retentive acetabular component. Success is
      not uniform. The Bousquet's acetabular component supports joint laxity and
      femoral malpositioning. This allows to keep the same original femoral component
      when the risk is too high for a cemented prosthesis or impossible for a non
      cemented prosthesis. CONCLUSION: This treatment of the recurrent dislocation is
      reliable with a short and simple operation.

PMID- 8560008
TI  - [Growth plate in primary osteochondritis dissecans of the hip: a prospective
      study with MRI].
AB  - INTRODUCTION: In Perthes' disease, epiphyseal necrosis impairs the function of
      the growth plate and may result in growth disturbances of the femoral neck. The
      physeal changes during active disease were prospectively evaluated with magnetic
      resonance imaging (MRI). MATERIALS AND METHODS: MRI was performed and radiographs
      were obtained with six-month intervals from the time of diagnosis up to two years
      in nine hips (eight patients). RESULTS: Normal growth plate was seen in MRI as a
      stripe of low signal intensity between areas of high signal intensity from the
      epiphysis and the metaphysis. Distortion, widening and partial disappearance of
      the growth plate were noted in the hips classified into Catterall groups 3 and 4.
      The physeal distortion was seen as anterior curling, and, in some hips, as a W
      shaped abnormality projecting down into the metaphysis. Delayed growth of the
      femoral neck, due to premature physeal closure, was noted in hips where the
      physeal deformation involved more than half of the growth plate. All pathological
      changes appeared on the MRI scans three to fifteen months after the first
      symptoms. The extent of the MRI changes did not correlate directly with
      Catterall's plain film staging. DISCUSSION: The distortion and widening of the
      growth plate seen in MRI probably reflect histological disarrangement of the
      physis due to an extensive epiphyseal necrosis. The physeal W-formation in MRI
      may represent a radiographic "metaphyseal cyst". Disappearance of the growth
      plate in MRI seems to indicate premature closure of the physis. CONCLUSION: It
      seems possible to predict premature closure with MRI even within fifteen months
      after the onset of Perthes' disease.

PMID- 8560009
TI  - [Sequelae in the knee extensor system following graft removal for the "Mac in
      Jones" type procedure].
AB  - PURPOSE OF STUDY: The aim of this study was to evaluate clinical and radiological
      sequelae following removal of part of the patellar tendon for A.C.L.
      reconstruction. MATERIALS AND METHODS: A consecutive and homogenous series of 100
      patients operated for chronic anterior instability (66 men, 34 women; age 16 to
      55 years, average: 28.5 years) was studied. The procedure involved a free
      patellar tendon graft harvested from the mid third of the tendon and including
      its bony attachments, and in particular a long strip from the patella and a strip
      10 centimeters long from the rectus femoris tendon for extra-articular
      reconstruction. Tendon graft sites were closed. Patellae and tibial tunnels were
      filled with bone debris from the drilling, and the pre-patellar fascia was
      closed. The mean follow-up period was 35 months. pain and radiological
      alterations (with pre-operative X-rays as reference) were studied, particularly
      for: calcifications, patellar height changes using the Insall, Blackburne and
      Caton methods, increase in patella tip length, femoro-patellar joint alteration.
      RESULTS: Calcification were found in: quadriceps tendon: 24 per cent of cases
      (always painless), Pre-patellar: 16 per cent of cases (usually less than 5 mm),
      Superior patellar tendon: 47 per cent of cases (only 2 cases being painful, no
      unaffected tendons were painful), Inferior patellar tendon: 7 per cent of cases
      (1 in the mid), Tibia tunnel: 26 per cent of cases. No cases required surgical
      removal. Patellar tip length did not increased significantly. Patellar tendon
      length decreased by 1.37 mm. Patellar height measured by the Insall, Blackburne
      and Caton methods was not significantly affected. The femoro-patellar joint was
      normal in 95 per cent of cases. There were five cases of remodelling, one being
      painful. CONCLUSION: Graft harvested from the extension system for A.C.L.
      reconstruction frequently resulted in radiological sequelae but were usually
      asymptomatic. In most cases these calcifications concerned the superior patellar
      tendon, quadricipital tendon and pre-patellar zone. Patella height was not
      affected.

PMID- 8560011
TI  - [Humeral retroversion and shoulder prosthesis].
AB  - PURPOSE OF THE STUDY: From a theoretical point of view, humeral torsion is
      described as the angle between the transcondylar plane and the posteromedially
      facing joint surface of the humeral head. In this study, humeral torsion was also
      identified as the angle between the anatomical neck of the humerus and at the
      inferior part the axis of rotation of the elbow and the axis of the forearm.
      MATERIALS: 60 cadaveric humeral shafts were obtained. The axis were defined and
      measured by CT Scans. METHODS: The orientation of the cartilage of the humeral
      head was determined as a line perpendicular to the limits of the joint area of
      the humeral head. The axis of the humeral anatomical neck was defined as the
      plane that contains both the long axis of the humerus and the center of the
      humeral head. The rotation axis of the elbow was defined as the line passing
      through the centers of the capitellum and the trochlear sulcus. RESULTS: The
      angle between the orientation of the humeral head and the orientation of the
      transcondylar line averaged 23 degrees. The angle between the humeral neck and
      the orientation of the transcondylar line averaged 38 degrees. The angle between
      the humeral neck and a line perpendicular to the axis of the forearm averaged 41
      degrees. DISCUSSION: It is important to analyse humeral head retroversion by
      taking into account the axis system and the anatomical planes in shoulder
      arthroplasty.

PMID- 8560010
TI  - [Macroscopic, histologic and ultrastructural study of 89 prostheses of anterior
      cruciate ligament excised because of prosthesis failure].
AB  - PURPOSE OF THE STUDY: This study concerns the etiology of failed synthetic
      anterior cruciate ligament (ACL) prostheses, and attempts to identify the primary
      mechanisms that lead to their premature rupture. MATERIAL AND METHODS: A total of
      89 failed and surgically excised ACL prostheses were retrieved from young and
      active patients (27 +/- 7 years) at various orthopaedic centres in France. Their
      average duration of implantation was 34 +/- 24 months. They were examined
      macroscopically, histologically and by scanning electron microscopy (SEM) to
      determine the model, the manufacturer, the surgical technique used at
      implantation, the extent of healing, the site of rupture, as well as the
      morphology of the damage fibers. RESULTS: Seventy two of these explants
      represented 6 different models. While all 6 were fabricated from polyester
      fibres, each had a different textile construction, and each were associated with
      a unique healing and mechanical response in vivo. SEM observations confirmed that
      abrasion of the textile fibres were a phenomenon common to all models, and were
      the primary cause of prosthesis failure. Such wear zones were particularly
      prevalent at the exit of the tibial tunnel and around the femoral condyle.
      Collagenic infiltration into the synthetic ACL was poorly organized and
      unpredictable. It did not increase with the duration of implantation. In fact in
      certain models, it appeared to have caused deterioration and fraying of the
      textile structure rather than serving as a reinforcing matrix around the
      prosthesis. DISCUSSION: A synthetic ACL prosthesis is to be preferred for
      patients who do not have tissue available for autologous ligamentoplasty. Yet
      none of the synthetic devices examined in the present study were capable of
      stabilizing the knee over the long term. Among the factors that influenced their
      failure we found that the three most common mechanisms were flat abrasion against
      an osseous surface, flexural and rotational fatigue of the fibres, and loss of
      integrity of the textile structure due to unpredictable tissue infiltration
      during healing. CONCLUSION: The results of the present study show that none of
      the current models succeed in replacing the natural ACL. Future improvements may
      be achieved by developing surgical procedures for implantation combined with a
      prosthesis made from fibres and textile structures which are more abrasion
      resistant and promote predictable and controlled tissue infiltration.

PMID- 8560012
TI  - [The Cortel-Dubousset device: prospective study on derotation].
AB  - PURPOSE OF THE STUDY: CD instrumentation has been presented as a system which is
      able to achieve a 3-dimensional correction of idiopathic scoliose. We performed a
      prospective study about the apex derotation following CD instrumentation.
      MATERIALS AND METHODS: 24 consecutive patients with idiopathic scoliosis were
      included in this study. On pre- and postoperative CT scans the rotation angle
      relative to the sagittal plane according to Aaro and Dahiborn (RA sag) were
      measured the pre- and postoperative changes were evaluated with paired T-tests
      together with the significance. Kruskal Wallis tests were performed to correlate
      the mean values of those calculated changes with the number of instrumented
      levels and with the different King types of scoliosis. RESULTS: There was no
      statistical significant increase or decrease of the rotation if we consider the
      sag without taking into account the type of curve. DISCUSSION: The different ways
      to measure rotation in scoliosis are presented. The limits of the method we used
      (RA sag) are also discussed. We reviewed the literature concerning derotation
      with CD instrumentation to compare it with our results. CONCLUSION: The
      evaluation of rotation in scoliosis is not easy. The CT scan seems to be the best
      method. Nevertheless, the postoperative changes of the morphology of the patient
      can be a factor of error in rotational measurement.

PMID- 8560013
TI  - [In vitro study of the properties of bioresorbable lactic acid polymer
      materials].
AB  - PURPOSE OF THE STUDY: The potential applications of biodegradable osteosynthesis
      implants present many advantages over conventional metallic devices. Polyesters
      of the poly and hydroxy-acid type were recognized early as serious candidates.
      These polymers have demonstrated a very good biocompatibility and are
      biodegradable in vivo. After biological and chemical testing poly L. lactic acid
      98 (PLA 98) was selected as a candidate. We used a static and dynamic
      investigation in vitro to assess firstly the material properties of PLA 98 and
      secondly how its characteristics could be modified within a physiological
      environment. MATERIAL: Michel Vert and colleagues have shown that polymers of
      lactic acid have a similar time to resorption providing they contain 98 per cent
      of the "L" form of the polymer. In vitro studies were assessed on bars made in
      PLA 98. METHODS: In a first time in vitro studies in traction and flexion on bars
      allowed an assessment of mechanical properties of PLA 98. In a second time
      stresses were applied on bars using a physiological environment (Haemacel - 37
      degrees C). In a third time we assessed the mechanical properties at the
      temperature of 37 degrees C with dynamic tests on bars in traction and flexion.
      RESULTS: The stress-strain curves on bars showed that the material is fragile.
      Sterilisation with ethylene-oxide did not affect the mechanical properties. When
      bars were placed in a thermostatically controlled (37 degrees C) physiological
      environment, the stress-strain curve showed that the material became ductile.
      With a temperature of 37 degrees C and with a frequency better than one hertz,
      the dynamic tests on bars showed that the material endurance is good up to 20,000
      cycles. At 37 degrees C and at the end of one month, the Young modulus and the
      maximal strain before breaking lose 50 per cent of their initial value.
      DISCUSSION: All things considered and as the digital value showed, the PLA 98
      appear to be ten times less strong than steel. In a physiological environment the
      mechanical properties improved due to hydratation of the polymer. The material
      become quickly ductile or malleable. This allowed transient loading without
      causing breakage. CONCLUSION: The mechanical properties of bioresorbable
      materials are very different from those of stainless steel and there is a
      learning curve in their utilisation. The PLA 98 polymer has demonstrated a very
      good biocompatibility and is totally biodegradable in vivo. With these results we
      think that PLA 98 can be used in clinical practice. Indications and clinical use
      should remain limited to bones regions with low applied stresses.

PMID- 8560014
TI  - [A new case of tibial stress fracture as a complication of knee osteoarthritis].
AB  - PURPOSE OF STUDY: Transverse stress fractures of the proximal tibia are
      associated with osteoarthritis of the knee. This uncommon complication is
      presented in this case report as a non-union form along with a literature review.
      CASE REPORT: A fifty nine year old black African woman who had a thirteen-year
      history of osteoarthritis in both knees, was seen for increasing pain in the
      proximal part of the left leg without demonstrative traumatism. This homemaker
      measured 155 cm for 85 kgs. Clinical and radiological examination revealed a non
      united stress fracture of the proximal part of the tibia and bilateral
      osteoarthritis of the knee with varus deformity (40 degrees on the left). A
      compression plate with bone grafting was used for treatment of the tibial non
      union. DISCUSSION: Eleven other cases have been published on the rheumatological
      and orthopaedical literature. All the twelve patients were female, elderly,
      overweight, had marked varus deformities and a long history of osteoarthritis of
      the knee. A non-united stress fracture was a complication of osteoarthritis in
      four cases and treated with a compression plate. CONCLUSION: Stress fractures of
      the proximal tibia are an unusual mechanical and an uncommon complication of
      osteoarthritis of the knee. Biomechanic is perhaps one of the possible
      explication of these tibial stress fractures.

PMID- 8560015
TI  - [Acute compartment syndrome as a complication of a distal forearm fracture:
      apropos of a case of a child].
AB  - PURPOSE OF THE STUDY: We describe a case of acute volar compartment syndrome of
      the forearm occurred after fracture of the diaphyseal-metaphyseal junction of the
      distal radius and ulna. MATERIAL: A 7-year-old child fell down steps and injured
      his left forearm. METHODS: After reduction, the patient developed clinical signs
      of volar forearm compartment syndrome. Measurement of intramuscular pressure by
      the saline injection technique confirmed the diagnosis. RESULTS: Early
      decompressive fasciotomy led to uneventful healing with no residual symptoms.
      DISCUSSION: We discuss the mechanism, diagnosis and treatment of this injury.
      CONCLUSION: The development of suspicious clinical signs should be supplemented
      by compartment pressure measurements to determine the need of surgical
      decompression.

PMID- 8560016
TI  - [Distal reconstruction of the Achilles tendon with a bone-tendon graft from
      extensor system of the knee].
AB  - PURPOSE OF THE STUDY: The authors describe a new surgical technique of tendo
      achilles reconstruction using bone tendon plasty from the patellar tendon, for
      rare chronic ruptures of the Achilles tendon flush within its calcaneal
      insertion, with distal loss of substance, requiring bone fixation. METHODS: The
      two step operation was carried out either in lateral or ventral decubitus (the
      latter two involving repositioning the patient): 1) Plasty harvesting. By a short
      anterior approach, we harvested either a strip of patellar tendon (10 mm wide)
      with a piece of tibia tuberosity or a strip of rectus femoris tendon (10 mm wide,
      up to 10-15 cm long) with a piece of patellar bone, in cases with a greater loss
      of substance. Tendo achilles reconstruction: following resection of fibrous
      tissue, and drilling of a blind calcaneous tunnel, the bone plasty is fitted into
      the calcaneous with interference screw for safety, the two tendon ends are
      superposed and sutured. The patient is placed in a cast for two months. RESULTS:
      Two patients (1 thirty-eight year old sportsman, 1 thirty-seven year old woman)
      were treated with a good morphological and functional outcome at two years.
      DISCUSSION: This new technique is compared with other available solutions:
      triceps plasty, other local tendon plasties, artificial plasties, It met the two
      criteria for these unusual ruptures: solid calcaneous fixation, no skin damage.

PMID- 8560017
TI  - [Allergic dermatitis caused by metallic implants in orthopedic surgery].
AB  - PURPOSE OF THE STUDY: Dermatitis due to metallic implants in orthopaedic surgery
      are uncommon complications and are difficult to diagnose. MATERIAL AND METHODS: A
      literature review found descriptions of 54 cases. All types of implants, even
      small in size such as screws or loops, made of stainless steel or chromium-cobalt
      alloys have been incriminated. There was no case related to titanium alloy.
      RESULTS: The clinical aspects were very different; all the forms of dermatitis
      are possible. The most frequent were eczemas (44 per cent), bullous dermatitis
      (11 per cent) and inflammatory forms (13 per cent). DISCUSSION: These dermatitis
      result either from immuno-allergic mechanisms or from cell-toxicity. There are
      two main diagnostic difficulties. 1--To confirm the responsibility of the implant
      in the dermatitis because the cutaneous lesions appears often generalized or
      localized in an area distant from the implant and because their emergence may be
      very belated, sometime after several years. 2--To distinguish some of these
      dermatitis and especially inflammatory forms, from sepsis. There is no current
      means to state positively this diagnosis without removing the implant. The
      microscopic tissues analysis surrounding the implant and the cutaneous patch
      tests using fillings of the implant itself are the only methods which appear able
      to confirm the diagnosis. There are no reliable means to detect risk subjects,
      the emergence of a dermatitis seems to be unpredictable. The specificity and the
      sensibility of the usual patch-tests are insufficient. CONCLUSION: The main means
      to prevent dermatitis is to reduce the production of metallic particles due to
      wear, fritting and corrosion. Management is based on removing of the incriminated
      implant. Treatment using drugs, including local applications or general
      dispensing of steroids, have generally a low efficiency.

PMID- 8560018
TI  - [Pseudarthrosis and delayed union of the distal phalanx of the long fingers.
      Apropos of 13 cases].
AB  - PURPOSE OF THE STUDY: The authors present 13 cases of delayed or non-union of the
      distal phalanx of the long fingers treated surgically. MATERIAL AND METHODS: The
      patients were all men aged from 41 years to 60 years. The involved digits were 4
      second, 2 long, 5 ring, and 2 little fingers. The operated side was the right
      side 5 times, the left one 8 times, the dominant one 4 times. Ten cases were due
      to inadequate treatment of the initial fracture. The three others cases had no
      clear explanation. Three types of incisions were used: transverse distal, lateral
      or an extended one combining the two previous. Bone stabilisation was made
      either, by longitudinal K wires or with a small cancellous screw. In 7 cases,
      bone grafting was needed. RESULTS: Bone healing was obtained in 9 cases in an
      average time of 9 weeks. Further procedures included: 2 distal amputations after
      septic conditions, 2 removals of distal bone fragment and 2 fusions of the distal
      interphalangeal joint. Overall results evaluated by the patients themselves were
      fair, including 2 excellent, 6 good (but 2 after distal interphalangeal joint
      arthrodesis), 2 mild (1 after distal interphalangeal joint arthrodesis), 1 poor
      and 2 failures. DISCUSSION: The type of skin incision was chosen according to the
      bone condition; distal in cases of fibrous nonunion when fibrous tissue removal
      and bone grafting were needed. Neither the type of bone stabilisation (pinning or
      screwing) nor the donor site of bone grafting influenced the final result.
      CONCLUSION: The authors would like to stress the importance of an adequate
      treatment of finger injuries in a emergency situation, considering the
      difficulties to restore secondarily a satisfactory functional outcome.

PMID- 8560019
TI  - [Results of orthopedic and surgical treatment of mallet finger by subcutaneous
      rupture of the extensor tendon. Apropos of a series of 216 cases].
AB  - PURPOSE OF THE STUDY: To assess the late results of orthopaedic and surgical
      treatment for mallet finger, two groups of patients were reviewed in a
      retrospective study. MATERIAL AND METHODS: 156 fingers (Group I) had conservative
      treatment and 60 fingers (Group II) some form of surgical treatment. RESULTS: In
      Group I, a dorsal custom-made perforated splint maintained the distal
      interphalangeal joint (DIP) in extension for an average of 54 days (st13). The
      mean delay of presentation was 22 days (st36). Initial lack of extension was 35
      degrees (st13). After an average follow-up of 154 days (st240), the lack of
      extension was only 7 degrees with an active range of flexion of 61 degrees
      (st11). 68 of these patients were reviewed for a long-term assessment (61
      months). At this time, lack of extension and range of flexion were not different
      (respectively 5 degrees- st10 and 61 degrees- st16). In Group II, 45 per cent of
      patients had initially some form of orthopaedic treatment. Delay between injury
      and consultation was 118 days (st250). Review with a mean follow-up of 5.6 years
      demonstrated a lack of extension and a DIP joint flexion of 12 degrees and 53
      degrees for tenodermodesis (14 cases), 2 degrees and 59 degrees for the Thompson
      and Littler procedures (14 cases), 1 degree and 55 degrees for the Fowler
      tenotomy (10 cases). DISCUSSION AND CONCLUSION: Orthopaedic treatment gave good
      functional results even in cases with delay of presentation. Surgery is only
      indicated in failure of conservative treatment. In absence of swan-neck
      deformity, tenodermodesis is a simple and effective technique. When a swan-neck
      is present, if the DIP deformity is corrected by PIP stabilization, the Fowler
      tenotomy is used. Otherwise, the Thompson and Littler operation allows to fully
      correct the deformity.

PMID- 8560020
TI  - [Quadriceps dysplasia and patellar tilt in objective patellar instability].
AB  - PURPOSE OF THE STUDY: Dysplasia of the vastus medialis, a well-known landmark of
      patellar instability, is difficult to point out pre-operatively. We propose the
      measurement of patellar tilt on the CT scans in order to appreciate abnormality.
      MATERIAL AND METHODS: We studied 3 well defined groups: 143 knees operated on for
      a true dislocation of the patella, either for the first time or a recurrent
      episode, 67 asymptomatic and nonoperated contralateral knees and 54 control
      knees. The patellar tilt in extension was measured on the CT-scan with the
      quadriceps relaxed and contracted. RESULTS: The results showed the increase of
      the patellar tilt as an characteristic factor of patellar instability (28.8 +
      10.5 degrees against 11.8 degrees + 5.7 degrees in the control group). Patellar
      tilt was not a consequence of the dislocation because it was also significantly
      increased in the asymptomatic contralateral group (17 degrees + 9 degrees).
      Quadricipital contraction increased the patellar tilt only in the two groups of
      patellar instability (+ 6 degrees) and asymptomatic contralateral group (+ 13
      degrees) but not in the control group (+ 1.6 degrees). The mean of the relaxed
      and the contracted quadriceps patellar tilt includes the dynamic trouble. We
      propose the threshold of 20 degrees to determine a pathological patellar tilt. In
      this case, sensibility is 90 per cent and the specificity is 91 per cent. In the
      other patellar instability factors, only severe trochlear dysplasias involved the
      patellar tilt. DISCUSSION: We think that the patellar tilt in extension is a
      landmark of a functional disorder of the whole quadriceps muscle more than the
      vastus medialis only. The mean of the relaxed and contracted quadriceps patellar
      tilt measures permitted to point out the border cases of this functional
      abnormality. This measurement is reliable and can be considered pathologic above
      20 degrees. The results of Insall's muscular plasty were only symptomatic because
      this procedure could not correct the effect of the quadricipital contraction.

PMID- 8560021
TI  - [Uncemented knee prosthesis. Results apropos of 58 cases with a minimum of 5-year
      follow-up].
AB  - PURPOSE OF THE STUDY: The aim of this study was to evaluate, after at least 5
      year's follow-up, the results of 64 PCA (TM) cementless total knee prostheses.
      MATERIAL: From 1984 to 1988, 13 male and 45 female patients (a total of 64
      prostheses including 6 bilateral) received PCA Primary prostheses. Both femoral
      and tibial components were implanted without cement. Mean age of patients was
      68.9 years (range: 35-81); mean patient height was 164.41 cm and mean weight
      76.74 Kg. The most frequent pathology was gonarthrosis: 43 cases of medial
      gonarthrosis and 15 of lateral gonarthrosis. There were 4 cases of rheumatoid
      arthritis and two post-traumatic degenerative arthritis. 52 knees were free of
      any previous surgical procedure. Of the 64 prostheses and the 58 patients: 6 died
      and 2 were lost to follow-up; 56 knees were reviewed. The longest follow-up is 9
      years for an average of 6.8 years. METHODS: Prosthetic review included clinical
      evaluation (Hungerford score based on 100 points, ISK rate based on 200 points)
      and complete radiological evaluation enabling the postoperative position of the
      implants to be examined. Radiolucencies were examined according to Ewald. X-ray
      study of polyethylene wear was performed based on the distance between the
      prosthetic condyle to the height of the metal tibial plateau. All patients were
      operated on by the same surgeon using the same procedure, and the same
      postoperative outcome. RESULTS: There were no local postoperative complications
      or any early reoperations. PHlebitis occurred in 12 per cent of cases. With the
      exception of 8 patients who were reoperated due to mechanical complications, the
      Hungerford score raised from 37.5 preoperatively to 88.3 postoperatively. The
      results of 43 of the 48 patients were rated good or excellent. The 200 point
      score rating gave 91 per cent of good and excellent results for knee examination,
      and 69 per cent of good and excellent results for knee function. Mean flexion
      angle was 107.8 degrees mean pain scored 45/50. Radiologically 75 per cent of
      operated patients had postoperative varus or valgus in the range 0-5 degrees as
      against 24 per cent preoperatively. The study of edge defects revealed the
      absence of any radiological abnormality on the femoral lateral projection in 85
      per cent of cases, and the absence of abnormality on the tibial anteroposterior
      and lateral projections in more than 60 per cent of cases. X-ray study of
      polyethylene wear was conducted on 49 cases: polyethylene wear was observed
      radiologically in 1 of 4 cases. There was no correlation between polyethylene
      wear and polyethylene thickness, postoperative axes, body weight or clinical
      results. 8 patients had to be reoperated due to mechanical complications: 2
      because of a tilting tibial plateau (due to a technical fault), 4 because of
      polyethylene wear and 2 because of patellar loosening (uncemented metal-back
      patellar implant). DISCUSSION: The implantation of femoral and tibial components
      of cementless PCA Primary fitted seems very satisfactory. With longer follow-up,
      we noted no tibial or femoral osteolysis signs such as those described by Engh,
      Peters or Berry in the USA. Stability of mid term radiographical results was
      commonly observed throughout our study. Only 5 very slight lateral displacements
      were noted: 3 cases of secondary LCP insufficiency with tibial posterior
      subluxation; in 2 cases the cause was R.A. CONCLUSION: The implantation of
      uncemented PCA Primary prosthesis caused non complications with respect to the
      femur. Regarding the tibia, only two reoperations were required because of tibial
      fixation failure due to a technical fault. The use of a hybrid prosthesis is not
      required. The microbeads used in PCA are effective but current availability of
      other materials promoting better bone growth (such as hydroxyapatite, titanium
      mesh) allows safe implantation of uncemented prostheses. PCA Primary polyethylene
      wear seems to develop steadily. This is why it should be replaced by the less

PMID- 8560022
TI  - [Results of sutures of the internal meniscus associated with reconstruction of
      the anterior cruciate ligament in chronic knee joint instability. Apropos of 42
      cases, 30 of them controlled by arthrography].
AB  - PURPOSE OF THE STUDY: Most authors agree on the importance of medial meniscus
      preservation in the case of A.C.L. reconstructive surgery. The purpose of this
      study was to analyze the anatomical results of sutures of medial meniscus tears
      by the means of arthrography. MATERIAL: Medial meniscus 42 sutures for peripheral
      tears at the posterior horn (length between 10 and 50 mm, 70 per cent greater
      than 20 mm) had been performed through an open procedure using a posterior
      approach. The average age of the patients was 24 years (17-54) with a clear male
      predominance (64 per cent). The average age at the time of injury was 22 years, 6
      months. METHODS: The patients were operated on by the same surgeon, with the same
      technique. Resorbable sutures were used spaced every-3 mm, and tightened outside
      the joint. The A.C.L. was reconstructed by a bone-patellar tendon-bone technique
      (modified K.G. Jones). A first series of 13-patients were no weight bearing
      allowed for 6 weeks post-operatively. A second series of 29 patients were allowed
      immediate partial weight bearing. All the patients were permitted active flexion.
      All the patients had been examined with a minimum of 6 months follow-up. They
      were all controlled clinically (results evaluated with the I.K.D.C. score) and
      with passive dynamic X rays to measure residual laxity. 32 patients had an
      arthrogram before the operation in the aim to compare with the postoperative
      arthrogram. 30 patients had an arthrogram after an average of 21 months. 12
      patients refused follow-up arthrograms. 9 patients had arthroscopy for pain or
      effusion. RESULTS: All the patients obtained a range of flexion-between 90
      degrees and 110 degrees at 4 weeks. A flexed contracture of 10 degrees was noted
      in only 1 case. Meniscal functional results were good for 32 cases after a mean
      follow-up of 4 years and 4 months. Arthrograms in 30 cases showed no residual
      tear in 19 cases (63 per cent), 3 cases had incomplete healing and 8 cases had
      failed. The healing was influenced by the size of the tear, its situation near
      the posterior wall. In the first series (no weight bearing), there were 2
      failures for 9 cases and 6 out of 21 in the second series and 3 incomplete
      healing. There was no correlation between meniscal functional results and
      functional ligamentous results evaluated with the I.K.D.C. score. 9 patients had
      an arthroscopy and 7 out of them a meniscectomy (after 17 months 3). CONCLUSIONS:
      This study confirms the possibility of healing following suture of peripheral
      medial meniscal tears in the case of ACL reconstructive surgery (even if the tear
      is long). The use of arthrogram, before the operation and for anatomical control
      after the operation, ensures complete healing (better than M.R.I. for the suture
      control). Arthrography is certainly a less invasive technique than arthroscopy.

PMID- 8560023
TI  - [Congenital convex talus. Methods and results of a single-stage surgical
      correction].
AB  - PURPOSE OF THE STUDY: The aim of this study was to emphasize the anatomical
      particularities of congenital vertical talus. We propose a one stage operative
      procedure adapted to the deformities. MATERIALS AND METHODS: A retrospective
      study of 24 children with congenital vertical talus was conducted. An etiology
      was observed in 58 per cent of cases and 42 per cent were considered as
      idiopathic. From a radiological analysis of 39 feet, we precise the anatomical
      particularities. We used anteroposterior and lateral X-ray and lateral stress
      views with maximal plantar and dorsal flexion. Most of the lesions were localized
      in the midtarsal joint. The irreducibility of the talonavicular dislocation is
      the predominant lesion. It is usually associated with a disorientation of the
      cubocalcaneal joint. The articular surfaces are disorganized with a dorsal
      orientation. There is a variable amount of equinus deformity in the hindfoot.
      However the talocalcaneal divergence angle is nearly normal. The forefoot is most
      of the times in eversion but sometimes in inversion. PROCEDURE: All children were
      treated initially by physiotherapy. We recommend operative treatment for them
      between one to two years old. After a soft tissue release, the talonavicular
      dislocation and the hind foot equinus deformity is reduced simultaneously. The
      subtalar joint is respected and not opened. Retracted tendons may be an obstacle
      to the reduction. They must be lengthened if necessary especially the Achilles
      tendon, the peronei, the extensors and the tibialis anterior. Reduction is
      maintained by a K wire transfixing the midtarsal joint. RESULTS: Clinical results
      were difficult to evaluate. Out of 24 operated feet, a satisfactory outcome had
      been achieved in 15 feet. All were plantigrad and 18 had a good cosmetically
      aspect. The only bad result concerned an old case which was not operated by this
      technique. DISCUSSION AND CONCLUSION: Conservative treatment is usually
      unsuccessful in congenital vertical talus. Numerous procedures have been
      advocated for the surgical correction of this deformity. Some authors advised
      excision of the navicular, full open peritalar release or extraarticular
      talocalcaneal arthrodesis. These are often extensive procedures and most are
      performed in two stages. Recently, one stage operative procedure was proposed. It
      allows a good correction with the respect of the subtalar joint and a lower risk
      of talus avascular necrosis. Furthermore it is more adapted to the deformity with
      a less extensive scar and a better respect of the anatomy.

PMID- 8560024
TI  - [Pelvic ring fractures in children. Apropos of 47 cases].
AB  - PURPOSE OF THE STUDY: The aim of this study was to report the different
      anatomical types, associated injuries, morbidity and mortality of pelvic ring
      disruption in child in Dakar traumatological centers. MATERIAL AND METHODS:
      [corrected] Forty seven children were admitted in two of three traumatology
      centers in Dakar between 1968 and 1992. This retrospective and intermittent study
      excluded tendon-bone avulsions and acetabular fractures. Twenty eight boys and
      nineteen girls presented a fracture with or without ring disruption according to
      Ducloyer and Filipe classification. In this first group, they make difference
      between an isolated or combined fracture and distinguished an anterior and a
      posterior one. Forty five children were treated by a non-operative methods.
      RESULTS: Forty three boys and girls sustained their injuries in a pedestrian
      motor vehicle accidents and 4 among were struck by a truck. A massive fracture
      dislocation with complete pelvic disruption was found in 70.3 per cent. Half of
      them (34.4 per cent) presented an anterior isolated anatomic type. In the other
      group the high energy forces caused major pelvic instability and also various
      associated soft-tissue injuries. The majority of complications were open pelvic
      fractures (21.1 per cent), genito-urinary (34.4 per cent), vascular (16.6 per
      cent), neurological and perineo-rectal injuries. Four children (8.4 per cent)
      died. At the last review others presented orthopaedic, genito-urinary,
      neurological or perineo-rectal sequelae. DISCUSSION: The frequency of pelvic
      fractures in child present a peak between 6 and 12 years old. These types of
      fractures are the results of a high energy injury in pedestrian motor vehicle
      accidents in Dakar suburbs. The anatomo-radiographic types had an interesting
      bimodal pattern: Among the benign types: a double fracture of the iliopubic ramus
      is dangerous for the bladder (1 case), and leads to a dysplastic acetabulum with
      time (1 case). Unstable fractures (70.3 per cent): some of them (23.3 per cent)
      present a complex dislocation of the pelvis. The present review focuses on double
      urethral injuries (2 cases), open pelvic fractures (10 cases) and mortal
      hemorrhagic shock (4 cases). The morbidity rate is high (38.4 per cent) caused by
      skeletal and soft-tissue sequelae and also management difficulties. CONCLUSION:
      Pelvic fracture in children requires early diagnosis and management. In our
      countries, morbidity and mortality of these injuries must decrease with the
      popularization of road safety, multidisciplinary management and improvement of
      working conditions.

PMID- 8560025
TI  - [False aneurysm of the posterior tibial artery complicating fracture of the tibia
      and fibula].
AB  - PURPOSE OF THE STUDY: Although tibia and fibula fractures are common, associated
      injury of the posterior tibial artery is rare. We present an unusual case of
      pseudoaneurysm of posterior tibial artery complicating a closed tibial and
      fibular fracture. MATERIAL: A 21-year-old man injured his left leg while playing
      football. METHOD: The diagnosis was suspected by the presence of persisting
      painful swelling at the fracture site. Echography, and later angiography
      confirmed it. RESULT: The patient was successfully treated with a saphenous vein
      interposition graft. The tibial fracture was stabilized with a Kuntscher nail,
      and five months after surgery the fractures healed. DISCUSSION: A review of the
      literature revealed only 11 civilian cases of pseudoaneurysm of the posterior
      tibial artery. The clinical signs, specific diagnosis and operative treatment are
      discussed. CONCLUSION: Our case emphasizes that attention must be paid to the
      vascular complications of fractures, that may not become evident until some time
      after the initial injury.

PMID- 8560026
TI  - [Chronic compartment syndrome of the foot. A case report].
AB  - PURPOSE OF THE STUDY: The aim of this paper is to present an unusual localization
      of a chronic compartment syndrome concerning the medial compartment of the foot.
      It emphasizes surgical treatment, using a fasciotomy procedure. MATERIAL AND
      METHODS: A thirty year old man was examined for a painful right foot. Pain was
      situated on the medial plantar aspect of the foot. It appeared following 15
      minutes of physical effort, especially after walking and running. It usually
      disappeared after a few minutes of rest and then, foot and lower leg examination
      were normal. The patient had comparative tissue pressure measurements at rest and
      after running, using a digital hand-held monitor (Stryker). A rest, the pressure
      was about 4 mmhg on both sides and it increased to 55 mmhg against 45 mmhg at the
      opposite side after exercise. It required more than 7 minutes vs. 30 seconds to
      return to their preexercise resting values. Thus a fasciotomy of the medial
      compartment was performed, using a medial approach. RESULTS: The patient had a
      good result at three months follow-up, recovering normal physical activity
      without any pain. DISCUSSION: The foot localization of an acute compartment
      syndrome has been recently described and it concerned only post-traumatic cases.
      The compartmental structure of the foot has been previously report. The chronic
      compartment syndrome of the lower leg was the reason for a pressure measurement
      study, at rest and following physical exercise; thus surgical fasciotomy was
      indicate when intracompartmental pressure rose above 30 mmHg in the presence of
      normal diastolic blood pressure, and particularly if delayed normalization of the
      pressure was greater than 5 minutes. The publications of foot pressure
      measurement are uncommon and they concerned only pressure at rest. In our
      observation, the profile of pressure of the patient and the result of fasciotomy,
      are in favour of chronic compartment syndrome. CONCLUSION: Chronic compartment
      syndromes require dynamic pressure measurements for an accurate diagnosis.
      Surgical fasciotomy may be sufficient to restore muscle function. We think this
      syndrome could happen in all anatomical compartmental structure when there is
      intensive use of muscles.

PMID- 8560028
TI  - [Dysbaric disease. Dysbarisms].

PMID- 8560029
TI  - [Native valve endocarditis caused by Staphylococcus aureus and streptococci. A
      comparative study].
AB  - OBJECTIVE: To know the validity and current prognosis of clinical prototypes
      assigned to streptococcal endocarditis (STREPEND) and Staphylococcus aureus
      endocarditis (SAE). PATIENTS AND METHODS: Fifty-four patients with SAE were
      compared with 43 patients with STREPEND diagnosed from 1984 to 1994 following a
      retrospective cohort study model. RESULTS: The incidence of SAE and STREPEND was
      0.21 and 0.17, respectively, per 1,000 hospital admissions. The acquisition of
      community endocarditis (non drug abusers vs. drug abusers) and nosocomial
      endocarditis was 74% (31% vs. 43%) and 26% for SAE; the corresponding values for
      STREPEND: 89% (70% vs. 19%) and 11%, respectively. The overall mortality rate for
      STREPEND/SAE was 9%/26% (among drug abusers there were no fatalities recorded),
      whereas in non drug abusers the mortality rate reached 41% and for nosocomial
      forms 36%. SAE was independently associated with drug abuse habits, right-sided
      heart infection, development of embolism and a high mortality rate. In contrast,
      by means of the multivariant analysis, STREPEND was independently associated with
      a subacute onset form, left-sided heart infection, cardiac surgery, and a low
      mortality rate. CONCLUSIONS: Traditional stereotypes of the two main etiologies
      for endocarditis are still valid, although at present it is important to
      differentiate nosocomial endocarditis and in non drug abusers. Chemoprophylaxis
      compliance is low for STREPEND: Given the poor prognosis of SAE at the left heart
      side a more aggressive surgical attitude would be warranted.

PMID- 8560027
TI  - [Multifocal bone tuberculosis: apropos of a case].
AB  - INTRODUCTION: Tuberculosis of bone is rare (10 to 20 per cent of all skeletal
      tuberculosis). The multifocal form is exceptional even in endemic countries of
      tuberculosis. It constitutes less than 5 per cent of all osseous tuberculosis.
      CASE REPORT: O.H. 34 year-old, Moroccan woman of black race not vaccinated
      against tuberculosis, with a contagion, complained for a year from scapular pain
      and weight loss. She noticed that two masses had appeared six months ago. The
      patient was feverish (38 degrees). The physical exam showed a non inflammatory
      mass 10 cm wide located in front of the left sacroiliac joint and seeming to be a
      cold abscess. The radiologic assessment showed a lytic image of the humerus upper
      extremity, the right iliopubis branch, the left ischium and the left iliac wing.
      The surgical biopsy of the humerus showed an evolutive caseo-follicular
      tuberculosis. The nuclear scan of bone found two other localizations in the
      fourth lumbar vertebra and the ninth left rib. We concluded to a multifocal bone
      tuberculosis with seven localizations: The upper extremity of both humerus Right
      pubis Left ischium Left iliac wing 4th lumbar vertebra 9th left rib. The
      treatment consisted in a specific antibiotic therapy for 6 months associated to
      the evacuation of the cold abscess. DISCUSSION: Multifocal bone tuberculosis is
      more frequent in young adults of black race. The beginning of the disease is
      progressive and the fistulas are the main reason of consultation. The radiologic
      lesions are not specific and have a geodic shape rimmed with an
      osteocondensation. Multifocal bone tuberculosis in black african predominate in
      flat bones. Otherwise in the white race it is located in the long bones
      extremities. The diagnosis of certitude is based on histologic findings of the
      peripheric bone lesion. The specific antibiotic therapy leads to the recovery if
      given early. Short protocols (9 or 6 months) are recently more used with success.

PMID- 8560030
TI  - [Ogilvie syndrome. Diagnostic and therapeutic attitude].
AB  - Ogilvie's syndrome (OS) is a clinical condiction with the symptoms, signs and
      radiological appearances of acute bowell obstruction but without any apparent
      mechanical cause. Diagnosis and treatment are often delayed and many patients are
      still inappropriately managed which in turn results in an increase in morbidity
      and mortality. We have reviewed our experience in eleven patients with OS in
      order to establish a system for their diagnostic and therapeutic management.

PMID- 8560031
TI  - [Prevalence of Helicobacter pylori infection in gastrectomy and vagotomy].
AB  - OBJECTIVE: To report the prevalence of Helicobacter pylori infection in patients
      undergoing gastrectomy or vagotomy plus pyloroplasty because of peptic ulcer
      disease. METHODS: Eighty-five patients were studied (mean age = 61 years; 85%
      males) who had undergone gastric surgery: Billroth I gastrectomy (n = 25),
      Billroth II (n = 51) and vagotomy plus pyloroplasty (n = 9). During endoscopy
      biopsy specimens were obtained from fundus and both sides of anastomosis for
      histological (hematoxylin-eosin) and microbiological (Gram stain and culture)
      investigations. RESULTS: The overall percentage of Helicobacter pylori infection
      was 43.6% (Billroth I = 40%; Billroth II = 37%; vagotomy = 89%) and no
      differences were observed between both types of surgical reconstruction. However,
      differences were indeed observed (p < 0.01) when comparing percentages of
      infection between patients undergoing gastrectomy and vagotomy. Among infected
      gastrectomized patients H. pylori was detected in fundus in 93% of cases, whereas
      the recovery rate from anastomotic mouth biopsies was only 72% (p < 0.05).
      CONCLUSIONS: The prevalence of H. pylori infection in gastrectomized patients
      (Billroth I and II) was low regarding the cause of surgery (peptic ulcer
      disease), and no differences were observed between both types of surgical
      reconstruction. The prevalence of infection after vagotomy and pyloroplasty was
      significantly higher. Among infected gastrectomized patients, H. pylori was
      detected more frequently in gastric fundus compared with biopsy specimens
      obtained from the anastomotic mouth.

PMID- 8560032
TI  - [Goodpasture syndrome: re-exacerbations associated with intercurrent infections].
AB  - A review is made of eleven patients diagnosed with Goodpasture syndrome from 1981
      1992 to study the possible causes of re-exacerbation episodes in this syndrome.
      Twelve episodes were detected in eight patients. Eight episodes were
      chronologically associated with intercurrent bacterial infections, one with
      discontinuation of therapy, one with volume overloading, and a concomitant
      infectious symptomatology was present in two patients, although no organism was
      recovered. All re-exacerbations manifested as pulmonary hemorrhage and most of
      them occurred in the early months after diagnosis. We therefore believe that an
      early diagnosis and aggressive therapy of intercurrent infections in this
      syndrome is recommended to avoid the re-emergence of pulmonary hemorrhage, which
      occasionally compromises patient survival.

PMID- 8560033
TI  - [Intracranial mass as single manifestation of sarcoidosis].
AB  - Neurological involvement in sarcoidosis occurs in 5-10% of cases and may adopt a
      great variety of forms, included space-occupying cerebral masses. The presence of
      these masses as single G manifestation of the disease, with no evidence of
      systemic involvement, is uncommon. In a review of the literature we found 15
      reported cases and we report here the case of a 74 year-old woman with a
      parietooccipital mass histologically diagnosed with sarcoidosis, with no evidence
      of systemic involvement. In most cases masses are supratentorial, evidenced by
      neuroradiological procedures and diagnosed by means of pathological
      investigation. Corticosteroids are the therapy of choice because of the favorable
      outcome of cases so treated.

PMID- 8560034
TI  - [Primary testicular lymphoma. Report of two cases].
AB  - Primary testicular lymphoma (PTL) is the most frequently diagnosed testicular
      tumor in men over 60 years, in spite of this circumstance it is a rare process.
      Two cases of PTL are reported, the first one in a child and the second in an
      adult. Both cases were intermediate grade lymphoma and had low stage (IEA),
      presenting initially as an enlargement of the testicle as the only symptom, the
      second case presented involvement by contiguity of the abdominal muscles.
      Immunohistological markers showed T nature in the first case, and B in the
      second. The treatment applied in both cases was orchiectomy and systemic
      chemotherapy using COP-BLAM/IMVP-16, in the child prophylaxis of the central
      nervous system using methotrexate was made. Response to treatment was good, the
      first patient achieved complete remission and his survival at present is 24
      months, the second patient died 5 month after diagnosis due to stroke without
      having completed chemotherapy but with an important reduction of the tumoral
      mass. A review of the literature on clinical, diagnostic and therapeutic issues
      is made.

PMID- 8560035
TI  - [Hematuria, a major sign. Causes and practical diagnosis].

PMID- 8560036
TI  - [Peritoneal pseudomyxoma].

PMID- 8560037
TI  - [Omeprazole and amoxycillin in the eradicating treatment of Helicobacter pylori].

PMID- 8560038
TI  - [Therapeutical savageness, diagnostic cruelty and medicine on the defensive].

PMID- 8560039
TI  - [Primigravida with rapid evolved liver insufficiency in third trimester
      pregnancy].

PMID- 8560040
TI  - [Systemic purpura in a 38-year old patient].

PMID- 8560041
TI  - [Cutaneous tumoral infiltration: intraarterial palliative chemotherapy].

PMID- 8560042
TI  - [Muscle pain and swelling in a HIV-positive patient].

PMID- 8560043
TI  - [Lynch syndrome. Report of a case].

PMID- 8560044
TI  - [Head of residents: a brilliant dawn].

PMID- 8560045
TI  - [Ischemic cerebrovascular incident associated with crack consumption].

PMID- 8560046
TI  - [Lichen planus and Hepatitis C virus serology].

PMID- 8560047
TI  - [Anesthetic pharmacology in recovery rooms].

PMID- 8560048
TI  - [Prolonged sedation with midazolam in critically ill patients undergoing
      artificial ventilation].
AB  - OBJECTIVES: To analyze the dose of midazolam needed for induction and maintenance
      of sedation, as well as its hemodynamic repercussions in critically ill patients
      requiring mechanical ventilation. PATIENTS AND METHODS: We studied 20 adult
      patients requiring mechanical ventilation for respiratory failure in the
      intensive care unit. An induction dose of 1 mg/min midazolam was given until the
      patient became drowsy (eyes closed but opened again) and this level of sedation
      was maintained by continuous intravenous perfusion. We calculated induction dose,
      maintenance dose and their correlation with age, weight, general state (APACHE-II
      index), liver function, hematocrit and blood chemistry. RESULTS: The induction
      dose was 4.76 +/- 3.4 mg and correlated with weight and plasma albumin levels.
      The maintenance dose of 6.4 +/- 3.97 mg/h did not correlate with any of the
      parameters studied. A statistically significant reduction in arterial pressure
      was observed. CONCLUSIONS: The sedation dose of midazolam in critically ill
      patients is related to weight and plasma albumin levels. Recovery time is related
      to mean maintenance dose.

PMID- 8560049
TI  - [Clinical care in a recovery room. Triennial review].
AB  - OBJECTIVES: To evaluate clinical practice in our intensive care unit over a
      period of 3 consecutive years (January 1991-December 1993). PATIENTS AND METHODS:
      Retrospective computer analysis of clinical data recorded for the 1157 patients
      admitted during the study period. RESULTS: Seven hundred thirteen men and 443
      women were admitted. Mean age was 58.8 years. Eighty-nine percent had undergone
      elective or emergency surgery, 7% were non surgical emergency admissions and 4%
      were transferred from other hospital wards. The mean stay was 3.8 days, though
      the mean stay for elective surgery patients was significantly shorter (p <
      0.001). We assess the usefulness of the APACHE-II scale applied during the first
      24 hours of admission, finding that mean scores were significantly lower (p <
      0.001) for the 1089 survivors (10.2 +/- 4.7) than for the 68 patients who died
      (23.6 +/- 9.4). The score on the APACHE II scale was above 16 for 82% of those
      who died. Overall mortality for the unit was 5.9%, though the proportion was
      statistically higher (p < 0.001) in emergency patients. Complications developed
      in 299, though the number of complications was significantly lower (p < 0.001)
      for elective surgery patients. The patients who died required more use of
      invasive monitoring and mechanical ventilation (p < 0.001). CONCLUSIONS: Our
      review shows that mortality, lengthy of stay in the unit and number of
      complications were all greater among emergency admissions. The patients who died
      had higher mean APACHE-II scores and required more care. Computerized data
      collection and later analysis is a useful way to assess clinical practice and
      facilitate future studies.

PMID- 8560051
TI  - [Postoperative analgesia in herniated disk surgery. Comparative study of
      diclofenac , lysine acetylsalicylate, and ketorolac].
AB  - INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in
      treating musculoskeletal pain and are theoretically ideal for treating
      postoperative pain of the lumbar column. OBJECTIVES: To compare the analgesic
      efficacy and side effects of treatment with 3 NSAIDs (lysine acetylsalicylate,
      ketorolac and diclofenac) in the treatment of pain after surgery for lumbar disc
      hernia. PATIENTS AND METHODS: We enrolled 75 ASA I-II patients undergoing
      discectomy because of lumbar disc hernia; balanced general anesthesia was used in
      all cases. The patients were randomly distributed in 3 groups based on type of
      analgesia given in the immediate postoperative period. Group A received lysine
      acetylsalicylate (1800 mg), group B received ketorolac (30 mg) and group C
      received diclofenac (75 mg). The analgesics were diluted in 100 mg of saline
      solution and administered through a peripheral vein over 10 min. We evaluated the
      analgesia attained on a visual analog scale (VAS) and the physiological response
      to pain was assessed by monitoring changes in arterial pressure, heart rate and
      breathing frequency. If analgesia was insufficient 30 min after administration of
      the drug, 200 mg of lysine cloximate was given as a top-up. The side effects of
      each drug were also recorded. RESULTS: VAS evaluation showed significant
      reductions in pain 60 min after administration in groups A and B and after 120
      min in group C. Nine patients in each group required lysine cloximate. There were
      no significant differences in physiological response among the 3 groups. No
      patient suffered major side effects. Mild side effects were reported most often
      in group B. CONCLUSIONS: The NSAIDs studied were inadequately for treating pain
      after surgery for lumbar disc hernia. Ketorolac was no better than the other
      analgesics studied but was associated with a higher number of mild side effects.

PMID- 8560050
TI  - [Comparative study of clonidine and lidocaine on the attenuation of the
      intraocular pressure increase associated with laryngoscopy and endotracheal
      intubation].
AB  - OBJECTIVE: To verify and compare the efficacy of clonidine and lidocaine for
      attenuating the ocular hypertensive response generated by manipulation of the
      laryngoscope and endotracheal intubation (EIT). PATIENTS AND METHODS: In this
      prospective double blind study 45 patients undergoing non-ocular surgery were
      divided into 3 groups according to pretreatment protocol: A, approximately 3
      micrograms/kg clonidine orally 90-120 min before surgery; B, 1.5 mg/kg
      intravenous lidocaine 1 min before EIT and C, control group. On all patients we
      recorded intraocular pressure (IOP), mean arterial pressure and heart rate at the
      following times: basal, just before EIT, immediately after EIT, 5 minutes later
      and 10 minutes later. RESULTS: The patients pretreated with clonidine had
      significantly lower IOP levels than did the control group at all measurements
      times; patients pretreated with lidocaine had lower IOP after induction and after
      intubation. IOP was significantly lower in patients who received lidocaine than
      in control group patients after EIT, although IOP levels with lidocaine were
      higher than with clonidine. CONCLUSIONS: Pretreatment with oral clonidine is an
      effective method for preventing increases in IOP after EIT, is more effective
      than pretreatment with lidocaine, and should therefore be used for that end.
      Intravenous lidocaine represents a valid alternative in emergency cases when the
      approximate wait time of 2 hours is contraindicated.

PMID- 8560052
TI  - [Effect of controlled hypotension using sodium nitroprusside on platelet
      aggregation].
AB  - OBJECTIVE: To determine the influence of sodium nitroprusside (SNP) on platelet
      aggregation when this agent is used to induce hypotension during surgery.
      PATIENTS AND METHODS: Spontaneous platelet aggregation (SPA) determined by
      impedance measurement and induced platelet aggregation (IPA) determined by
      turbidimetry were studied in 30 subjects scheduled for elective ear, nose or
      throat surgery. Fifteen patients in the SNP group (SNPG) received SNP in doses
      adjusted to maintain a mean arterial pressure of 50 mmHg. Another 15 patients who
      did not receive SNP served as controls. RESULTS: SPA increased progressively in
      both groups. The greatest increase occurred after anesthetic induction (control
      group +172%, SNPG +48%); the highest level recorded was reached on the morning of
      the first day after surgery (control group +215%, SNPG +46%). IPA decreased after
      anesthetic induction (control group -21%, SNPG -40%) and stayed down throughout
      surgery. IPA was higher on the first morning after surgery than before the
      operation (control group +35%, SNPG +2%). SPA was significantly higher 60 minutes
      after start of surgery than before surgery in the control group; IPA and SPA were
      likewise higher in these patients the morning after surgery. CONCLUSIONS:
      Platelet aggregation increases during surgery and in the immediate postoperative
      period. This increase is attenuated when SPA is given to induce hypotension. SPA
      should be determined by measurement of impedance in whole blood when the nature
      of platelet aggregation during surgery is being studied, given that early
      increases in IPA can be masked as a result of the low sensitivity of
      turbidimetry.

PMID- 8560053
TI  - [Analysis of knowledge about the anesthesiology specialty among a population of
      medical students].
AB  - OBJECTIVES: To analyze the knowledge of anesthesiology possessed by a group of
      medical students representative of medically trained individuals who have not yet
      worked in a hospital. MATERIAL AND METHOD: Students in their fifth year of
      medical studies at the University of Valencia were invited to voluntarily and
      anonymously answer a questionnaire with dichotomous and multiple choice responses
      covering general and specific aspects of anesthesiology. The survey also
      collected personal and epidemiological data. One hundred eighty-five
      questionnaires were returned. RESULTS: The results obtained were analyzed for
      correlations with epidemiological and personal data (sex, information received,
      prior anesthesia); no significant correlations were found between these data and
      correct response. It was believed by 78.4% that the anesthesiologist's function
      during surgery does not go beyond warning the surgeon of changes in vital signs.
      Nevertheless, 76.2% asserted that the anesthesiologist's function is to protect
      the patient during the perioperative period. CONCLUSION: In comparison with the
      general population, medical students' training has left them with inadequate
      understanding of anesthesiology.

PMID- 8560054
TI  - [ 2 cases of tension pneumopericardium after unilateral lung transplantation].
AB  - We present 2 patients who developed tension pneumopericardium after undergoing
      unilateral lung transplantation, describing their clinical evolution after
      surgery until the diagnosis of tension pneumopericardium. In both cases
      aspiration of air from the pericardium resulted in improved hemodynamic status.
      Tension pneumopericardium is rare in adults. Our patients were at high risk due
      to the difficulty of ventilating native and implanted lungs with different
      compliances. Moreover, the passage of air from the mediastinum to the pericardium
      is facilitated by the large opening made in order to dissect the pulmonary veins.

PMID- 8560056
TI  - [Patient with tricuspid atresia undergoing orthopedic surgery: anesthetic
      considerations].
AB  - We describe a 52-year-old patient with rheumatoid arthritis, interventricular
      communication and pulmonary stenosis. After an accidental fall she was scheduled
      for total hip replacement. The main objective of anesthetic management was to
      preserve pulmonary blood circulation at arterial pressures that would assure
      adequate tissue perfusion. Other objectives were to maintain hydration to prevent
      decreases in hematocrit levels, avoid systemic embolization and allow for
      antibiotic prophylaxis.

PMID- 8560055
TI  - [Application of the laryngeal mask in pediatric anesthesiology].
AB  - To analyze problems with inserting, maintaining and removing a laryngeal mask in
      children, as well as to assess the possible involvement of certain factors
      (experience with the laryngeal mask, type of anesthesia, duration of surgery,
      type of surgery, obesity, etc.) in favoring the development of complications. One
      hundred eighty-nine children undergoing a variety of surgical procedures under
      general anesthesia were studied; patients with full stomachs and/or a history of
      hiatus hernia were excluded. The agent used for anesthetic induction and the
      method of ventilation were chosen by the anesthesiologist responsible for each
      case. Variables monitored in all patients were continuous ECG, heart rate,
      systolic and diastolic arterial pressure, capnography, pulse oximetry, airways
      pressure and respiratory rate. Values were recorded at five times: before
      induction (T1), immediately after induction (T2), after placement of the
      laryngeal mask (T3), before removing the laryngeal mask (T4) and after removing
      the laryngeal mask (T5). Correct insertion was achieved on the first try in 85%.
      The remaining 15% required 2 or more tries. There were no cases in which a
      tracheal tube or face mask were required. We found no correlation between type or
      duration of surgery and the occurrence of complications. Complications were more
      frequent when the laryngeal mask was placed by inexperienced personnel, when
      inhalational anesthetics were used for induction and maintenance, and when a No.
      1 laryngeal mask was used. Adequate ventilation was provided for the patients who
      required it with an airways pressure between 8 and 18 cmH2O, arterial oxygen
      saturation over 98% and end-expiratory CO2 pressure under 35 mmHg. Cardiovascular
      repercussions were slight and hemodynamic stability was good.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8560057
TI  - [Cervical epidural anesthesia for carotid mycotic aneurysms].
AB  - Extracranial mycotic aneurysms of the carotid are unusual. We present such an
      aneurysm of the right primary carotid caused by enteritis due to Salmonella in a
      75-year-old patient at high risk for surgery (myocardial ischemia evolving over 3
      months) and with coexisting stenosis of 75% of the left internal carotid.
      Endarterectomy of the left internal carotid, with shunting, was performed, after
      which the right primary carotid was tied during the same operation. Epidural
      anesthesia to C6-C7 was provided through a catheter supplemented with an
      intravenous propofol infusion. Neurological and hemodynamic variables monitored
      during surgery were stable. No neurological deficits or myocardial ischemic
      changes were recorded. Three months after discharge the patient was asymptomatic.

PMID- 8560058
TI  - [Neuromuscular relaxants in the recovery room].

PMID- 8560059
TI  - [Malignant hyperthermia or neuroleptic malignant syndrome?].

PMID- 8560060
TI  - [Reduction of the need for isoflurane and of postoperative pain with
      preanesthetic intrathecal morphine].

PMID- 8560061
TI  - [High-frequency ventilation in a patient with bilateral tension pneumothorax
      caused by barotrauma and severe bronchospasm].

PMID- 8560062
TI  - [Intradural anesthesia in cesarean sections].

PMID- 8560063
TI  - [Anorectal malignant melanoma].
AB  - The cases of four patients who are carriers of primitive anorectal malignant
      melanoma are presented, reviewing at the same time the medical literature
      available. The clinic of all these patients was similar: pain, proctorrhagia,
      tumors, tenesmus, hemorrhoids and changes in the intestinal rhythm. One of these
      cases was similar to thrombosed hemorrhoids, and for this reason we believe that
      all of the parts that are removed should be biopsied. The prognosis of this
      pathology is in general adverse, notwithstanding the treatment received. There
      are very few cases on record that have survived more than 5 years, with early
      diagnosis and treatment with an abdominal-perineal resection. Radiotherapy and
      chemotherapy can reduce the size of the lesion but it is acknowledged that the
      prognosis will not change.

PMID- 8560064
TI  - [Laparoscopic hysterectomy. Results in 80 cases].
AB  - Our experience is based on laparoscopic hysterectomies performs from August 1992
      to May 1994. The purpose of the initial surgical objective is described, as well
      as different variations of the technique. The procedure was systematized, the
      operating time was diminished to a considerable extent, thus avoiding intra
      operatory complications. Pre-operatory diagnosis and histopathological findings
      were enumerated. Intra-operatory and post-operatory complications were evaluated.
      With an increasing development of the technique, a shorter operating time was
      made possible. The length of hospital stay and its quality were unrelated to the
      operation time. A quick recovery was reached as regards complete activity of the
      patients. Laparoscopic hysterectomy performed by an endoscopic-gynecologist
      surgeon represents an alternative and a new way of thinking.

PMID- 8560065
TI  - [Pulmonary lymphomatoid granulomatosis: report of a case].

PMID- 8560066
TI  - [Proposal: education of human resources in basic biomedical sciences].

PMID- 8560067
TI  - [Structure of dental services in a social security system: Cordoba, Argentina].
AB  - We describe here the results of a survey carried out to determine the nature,
      extent and distribution of the dental service provided by the Board of the
      University Personnel Social Assistance (Direccion de Asistencia Social del
      Personal Universitario [DASPU] From 1988 to 1990. Such survey was performed on
      the bases of a representative sample of assistance recipients. The greatest
      dental service demand was registered among the group of persons of 25-44 years
      old (40.3% of the total), although the rendered services per person/years
      increased with the member's ages. Restorative Dental and Prosthesis registered
      the highest occurrence (50.2% of the total). Preventive Odontology practices were
      infrequent (1.2%) while Odontopediatric was the less demanded (0.3%). 31.8% of
      the assistance was provided by DASPU own services, Prothesis being the most
      predominant kind. As for external effectors (62.3%), the most frequent were those
      of Dental Operating. It is concluded that the demanded dental services were
      mainly curative and reparative. The reorganization of the Odontology Service may
      increase the system' performance efficiency and effectiveness.

PMID- 8560069
TI  - [Measuring pneumonology activity at the hospital: more and better?].

PMID- 8560068
TI  - Serum levels of prolactin and alpha-melanotrophin and structure of the ovary
      during the reproductive cycle of Columba livia (domestic pigeon).
AB  - Given the importance of the hormones prolactin and alpha-melanotrophin in the
      regulation of the mammalian reproductive cycle, it was decided to assess their
      serum levels during the reproductive cycle of Columba livia (domestic pigeon).
      Female pigeons were utilized in the stages of egg-laying, incubation and rearing.
      Simultaneously, the structural changes of the ovary in the aforementioned periods
      were studied. The levels of prolactin and alpha-melanotrophin showed similar
      behaviour. The low concentrations found in the period of egg-laying (x +/- s =
      4.3 +/- 0.6; 3.5 +/- 0.26 ng/ml) increased significantly during incubation (x +/-
      s = 6.5 +/- 0.7 ng/ml; 6.6 +/- 1.7 ng/ml) to reach the maximum value in the
      rearing period (x +/- s = 10.33 +/- 1.8 ng/ml; 13.6 +/- 1.9 ng/ml). Accompanying
      these changes a marked predominance of the medullary zone over the cortex and
      lack of developing follicles were found in the rearing state.

PMID- 8560070
TI  - [Hematopoietic growth factors in iatrogenic neutropenia in oncology].

PMID- 8560071
TI  - [Gene transfer: an economic challenge].

PMID- 8560072
TI  - [Mechanism of antibiotic resistance in bacteria responsible for respiratory
      infections].
AB  - Bacterial resistance is both a frequent phenomena and in perpetual evolution;
      currently it effects all antibiotics. The acquisition of resistance is a result
      of chromosomal mutations or is a contribution of genetic material either as
      plasmids or transposons. The principle mechanisms which can be isolated or
      associated can be grouped together under changes of bacterial permeability which
      alters the target of the anti-infectious agents; or the synthesis of enzymes
      which inhibit the activity of the antibiotic. Some micro-organisms such as
      Staphylococcal aureus, Streptococcus pneumoniae, Haemophilus influenzae,
      Pseudomonas aeruginosa, and certain enterobacteria have developed resistance to
      varying degrees against the antibiotics initially or more recently introduced
      which pose, in some cases, very real therapeutic problems. The prescribing doctor
      should recognise the principle bacterial phenotypes which are resistant, as well
      as the rules of association of the different antibiotics in order to institute an
      effective anti-infectious regime, which allows the cure of the patient and limits
      any introduction of resistance or the selection of resistant mutants.

PMID- 8560073
TI  - [Role of hematopoietic growth factors in bronchial cancerology].
AB  - Haematological growth factors constitute a major development in haematological
      and oncological practice. There are many questions raised as to their place and
      their optimal usage in the treatment of bronchial cancer. Growth factors enable
      the dose of chemotherapy to be increased by 20-40%, the limiting factor being
      thrombocytopenia and non-haematological toxicity. Nevertheless, a dose response
      relationship has never been clearly shown with chemotherapy for small cell and
      non-small cell carcinoma. Prescribing growth factor prophylactically enables a
      reduction in both the depth and duration of neutropaenia. Randomised studies
      which have evaluated G-CSF and GM-CSF for prophylaxis of infections in patients
      treated for small cell carcinoma lead to the same conclusions: a diminution in
      febrile episodes with neutropaenia, the duration of hospital stay and in the
      prescription of antibiotics. It seems justifiable to prescribe growth factors in
      patients presenting with a febrile illness and aplasia after the first treatment
      without growth factor in small cell carcinoma. It seems equally legitimate to
      prescribe these drugs in non-small cell carcinoma which have responded to
      chemotherapy at the price of aplasia. Outside these circumstances, it does not
      seem appropriate to prescribe these factors as first intention to those patients
      receiving conventional doses of chemotherapy who had not been treated before.
      There does not yet exist clear data for their use in established febrile
      conditions. The economic assessment has been limited to studies of minima-listing
      costs. No study of cost-effectiveness and cost-utility has been carried out to
      date.

PMID- 8560074
TI  - [Role of expiratory muscles in chronic obstructive respiratory insufficiency].
AB  - We have studied the pattern of abdominal muscle (transversus abdominis, external
      oblique and rectus abdominis) contraction and its mechanical correlates in
      patients with CAO. When breathing at rest, many stable patients with severe CAO
      contract the abdominal muscles during expiration and this expiratory contraction
      is usually confined to the transversus muscle. Moreover, this contraction most
      often makes expiration a mechanically active process and is an important
      determinant of intrinsic positive end-expiratory pressure (PEEPi) in such
      patients. The pathophysiologic implications of these findings are discussed.

PMID- 8560075
TI  - [Upper airways and sleep apnea syndrome].
AB  - The imaging techniques of the upper airway (UA) now permit a description of the
      characteristics of pharyngeal collapse during the course of obstructive apnoea.
      The start is oropharyngeal with active movements anterior and posterior of the
      soft palate and a falling back of the tongue. The extension occurs almost
      systematically towards the hypopharynx. A displacement of the hyoid bone and of
      the cervical spine is noted synchronously with thoracoabdominal movements. These
      imaging techniques of UA show the occurrence of passive pharyngeal collapse
      during certain types of central apnoea. In snorers and in apnoeics, there is a
      reduction of the calibre of the pharynx. However, these abnormalities are not
      specific and do not enable the diagnosis to be confirmed nor an estimate of the
      severity of the sleep apnoea syndrome. Cephalometry and computed tomography of
      the pharynx should be carried out particularly when a uvulopalatopharyngoplasty
      (UPPP) is envisaged. For practical purposes, the existence on cephalometry of
      retrognathism with an MP-H > 24 mm and a PAS distance of < 5 mm is associated
      with a poor result for UPPP. The same thing applies when macroglossia or a
      reduction of the surface of the hypopharynx is found on computed tomography.

PMID- 8560076
TI  - [Retrospective study of pneumoconiosis in Champagne-Ardenne].
AB  - This study was carried out in two departments of Champagne-Ardenne. The aim was
      to assess the level of retrieval in patient population suffering from
      pneumoconiosis who were hospitalised with this disorder, compared to another
      population who had contracted the same disease in the working environment and
      were known to the local social security benefit office in the North East
      (CRAMNE). A list of 77 names of hospitalised patients had been obtained following
      requests for mineralogical analysis addressed to a specialised national
      laboratory. A second list of 59 names of patients who were receiving compensation
      for pneumoconiosis was provided by CRAMNE. Five subjects were common to both
      populations. The discordance between the two was partly explained by the non
      recognition of the system of compensation for indemnifiable occupational disease.
      The recruitment of hospitalised patients leads to a bias which influences the
      distribution of pneumoconiosis patients. Subjects presenting with the most
      consistent abnormalities in pulmonary function did not all figure amongst the
      notified cases.

PMID- 8560077
TI  - [Video thoracoscopy of pulmonary nodules. Can one avoid preoperative markers?].
AB  - For a period of 35 months, 50 patients presenting with a total of 61 peripheral
      pulmonary nodules were operated on under videothoracoscopy. As a matter of
      principle none of these nodules were marked radiologically pre-operatively. All
      the scanners were reviewed retrospectively by a radiologist and a thoracic
      surgeon without knowing the results of the thoracoscopic intervention: 23 of
      these patients on the evidence would have quite obviously required preoperative
      marking (group I), and 27 would have been presented for direct thoracoscopy
      (group II). In group I there was only one group of nodules which could not be
      localised and by necessity, a thoracotomy was required. In group II, two nodules
      could only be localised thanks to a mino-thoracotomy. The level of failure was
      between 4 and 7%, and was identical to that found in the literature for different
      techniques of pre-operative radiological marking: these techniques were often
      complicated by a pneumothorax and intrapulmonary haemorrhage. These techniques
      for marking are used extensively. Prospective studies based on precise and
      complete criteria should enable better definition of rare cases which might
      benefit.

PMID- 8560078
TI  - [Pulmonary embolism and the level of thrombosis. A prospective study of 155
      patients].
AB  - This study was designed to assess the risk of associated pulmonary embolism
      according to the level of deep venous thrombosis. From March 1992 to March 1994,
      328 patients were referred to medical units for suspected deep venous thrombosis,
      with recent clinical signs, less than a week. Each patient underwent contrast
      venography and/or duplex ultrasounds of lower extremities, ventilation and
      perfusion lung scan within 48 hours and angiography in case of low or
      intermediate pulmonary embolism probability. Diagnosis of deep venous thrombosis
      was confirmed in 155 patients; location was distal in 41, proximal in 114; an
      associated pulmonary embolism was found in 66 patients (10 with distal, 56 with
      proximal deep venous thrombosis); odds ratio was 2.99 (95% Cl: 1.2-3.13).
      Significantly higher risk of associated pulmonary embolism when deep venous
      thrombosis involves proximal veins is confirmed, but as many as 10 out of 41
      patients with distal thrombosis also had an associated embolism. Management of
      both distal and proximal deep venous thromboses appears identical.

PMID- 8560079
TI  - [Chronic course of reactive bronchial dysfunction syndrome. Apropos of 6 further
      cases].
AB  - The reactive airways dysfunction syndrome (RADS) occurs as a persistent bronchial
      hyper-reactivity with asthmatic-type dyspnoea and occurs after a single and
      massive inhalation of irritant gases, smoke or vapours, in subjects who had
      previously had no respiratory disease. We report six cases in patients without
      any previous asthmatic history or history of atopy who had developed RADS after
      being exposed to different irritants. The symptoms evolved over 5-84 months after
      the initial accident. Only moderate airflow obstruction was found, but all
      subjects had bronchial hyper-reactivity to methacholine. A bronchial biopsy was
      performed in a patient and this showed moderate sub-epithelial mononuclear
      inflammatory infiltrate. A specific feature of this syndrome is the facility to
      inaugurate a susceptibility to asthma after the initial accident and for this to
      progress of its own accord with secondary aggravation, even in the absence of new
      exposure to the irritating agent. Its frequency is probably under-estimated
      because it remains little known in France. It is very important both to recognise
      and notify inhalational accidents at work to be able, should the nedd arise, to
      identify the worker and to enable a move to a different job if necessary.

PMID- 8560080
TI  - [Explanatory indicators of the length of stay in a pneumology department].
AB  - BACKGROUND: Utilization of Diagnosis Related Groups (DRGs') for hospital payments
      in France. OBJECTIVES: To search the variations and the explicative factors of
      length of stay in a pneumologic unit, to analyse the relevance of the indicators
      by using the DRG's and the supplementary variables in a medical and economical
      perspective. SETTING: Pneumologic unit of Limoges' teaching hospital. METHODS:
      From 1-4-93 to 31-5-94, a prospective study analysed 1081 stays (one-day-longer)
      by the medical unit summary and by some variables describing the stay (planned
      admission, appropriateness), the patient (physical mobility at entrance, severity
      of disease), the procedures (physiotherapy, social needs). Statistical tests
      associated univariate analysis, linear and logistic regressions, hierarchic
      segmentation. RESULTS: DRG's explain 23% of logarithm length of stay. The
      mathematical model has separated five variables, which are associated with an
      increase of length of stay (age, number of procedures, physical mobility at
      entrance, social complexity, intensity of physiotherapy), one associated with a
      decrease of length of stay (planned admission). CONCLUSION: DRG's, alone, do not
      describe the dispersion of the length of stay, which is usually used to assess
      the consumption of resources during an hospitalization. The record of
      supplementary variables needs further studies, to improve the patients'
      classification.

PMID- 8560081
TI  - [Pulmonary metastases of glioblastoma].
AB  - Extracranial metastases arising from primary brain tumors are very unusual. We
      report a case of glioblastoma with intra-thoracic spread characterized by
      mediastinal lymph nodes metastasis and bronchial, lung parenchyma and pleura
      carcinomatous lymphangitis. Pathologic findings are consistent with non
      differentiated cell proliferation but Glial Fibrillary Acidic Protein
      immunodetection can be helpful to relate such a non-differentiated cell
      proliferation to its glial origin. The mechanisms of extra-cerebral spread are
      discussed according to autopsic findings and to the data reported in the
      literature.

PMID- 8560082
TI  - [Idiopathic spontaneous pneumomediastinum: a not to be mistaken diagnosis in
      chest pain].
AB  - We report two cases of mediastinal emphysema occurring without etiologic factor.
      Chest pain and subcutaneous emphysema are the most prevalent symptoms. In the
      absence of oesophagus related symptoms, a single chest radiograph is usually
      sufficient to make the diagnosis. In this paper, we recall the main radiographic
      signs, physio-pathological mechanisms, and differential diagnosis of spontaneous
      pneumomediastinum.

PMID- 8560083
TI  - [Diffuse alveolar hemorrhage secondary to oral anticoagulant use].
AB  - We report a case of alveolar haemorrhage in all probability, attributable to the
      use of anti-vitamin K. The favourable outcome of this type of disease has rarely
      been reported with anticoagulants and fibrinolytics, most frequently in a
      disturbed haematological setting with disseminated intravascular coagulation or
      profound thrombocytopaenia. One should not forget this diagnosis in cases of
      acute respiratory failure in association with an alveolar syndrome in an exposed
      patient due to the fact that the outcome is generally favourable after correcting
      the disturbed coagulation.

PMID- 8560084
TI  - [Fatal acute silicosis caused by voluntary inhalation of scouring powder].
AB  - We report a case of acute fatal fibrosing silico-proteinosis occurring in nine
      months in a young woman who had voluntarily inhaled scouring powder. We recall
      the reports in the literature of the subacute or chronic forms associated with
      systemic diseases occurring after such inhalational practices. We recall the need
      for specific questioning and to complete the study, the need for microscopy and
      electron-microscopy associated with X-ray defraction, either on the alveolar
      lavage fluid or on a lung biopsy.

PMID- 8560085
TI  - [Phrenic stimulation].

PMID- 8560086
TI  - [Medical thoracoscopy].

PMID- 8560087
TI  - [Noninvasive ventilation using nasal mask in mucoviscidosis].

PMID- 8560088
TI  - Assessment of right ventricular diastolic function by pulsed Doppler
      echocardiography in chronic pulmonary disease and pulmonary thromboembolism.
AB  - We evaluated right ventricular (RV) diastolic performance in 12 healthy subjects
      (control), 25 patients with chronic pulmonary diseases (CPD) and 6 patients with
      chronic pulmonary thromboembolism (PTE). Flow velocity patterns were determined
      by the pulsed Doppler technique. The values determined included acceleration time
      (AT), deceleration time (DT), and the ratio of the atrial contraction wave (A) to
      the rapid filling wave (R) (A/R ratio) from flow velocity patterns in the RV
      inflow tract. DT was significantly prolonged in the CPD and PTE groups compared
      with the control group, indicating dysfunction during the early (middle) filling
      period. The prolongation was marked in those patients with pulmonary
      hypertension. The A/R ratio was significantly higher in the CPD and PTE groups
      than in the control group, indicating a decrease in RV compliance. The A/R ratio
      increased slightly with the increase in the end-diastolic volume index. These
      results suggested that the pressure overload plays an important role in RV
      diastolic dysfunction in patients with pulmonary disease, and that preload
      contributes to the dysfunction.

PMID- 8560089
TI  - Canine pulmonary hypertension model induced by pulmonary artery embolization of
      gelatin sponges.
AB  - We attempted to develop a pulmonary hypertension model in dogs by gelatin sponge
      embolization. We then monitored right-ventricular pressure overload by
      echocardiography. Gelatin sponges (Spongel, Yamanouchi, Tokyo) were homogenized
      and mixed in normal saline (0.6 mg/ml). The mixture was administered via the
      jugular vein to general pulmonary emboli. Repeated administration of the sponges
      increased the mean pulmonary arterial pressure and caused right ventricular
      pressure overload. The degree of pulmonary hypertension was proportional to the
      volume of gelatin sponge injected. Echocardiography, performed both before and
      after embolization, proved useful assessing for the degree of right-ventricular
      pressure overload.

PMID- 8560090
TI  - Can interstitial pneumonia as the sole presentation of collagen vascular diseases
      be differentiated from idiopathic interstitial pneumonia?
AB  - We prospectively followed 68 patients diagnosed as idiopathic interstitial
      pneumonia (IIP) over a period of 1-11 years. Thirteen patients (19%) subsequently
      developed systemic manifestations of collagen vascular diseases (CVD) and were
      diagnosed as having had interstitial pneumonia as the sole presentation of CVD
      (CVD-IP). Compared with the 55 IIP patients, the 13 CVD-IP patients were
      relatively younger, predominantly female, and had a lower incidence of dust
      inhalation in their history. They also had a higher erythrocyte sedimentation
      rate, higher incidence of the x-ray finding of discoid atelectasis in the lower
      lung fields, and a better prognosis than the IIP patients. However, these
      features did not clearly distinguish the two groups. We conclude that the
      patients clinically and/or histologically defined as suffering from IIP cannot be
      distinguished from CVD-IP patients before systemic signs of CVD appear in the
      latter group.

PMID- 8560091
TI  - Measurement of urinary desmosine as an indicator of acute pulmonary disease.
AB  - A modified radioimmunoassay (RIA) for desmosine in the urine was investigated as
      a tool for the rapid estimation of lung elastin catabolism. Cystic fibrosis (CF)
      and oxygen toxicity were chosen as conditions that might show altered elastin
      destruction. Using an antibody bound to magnetic particles the RIA was adapted to
      handle large numbers of samples requiring only 50 microliters or urine. The
      experiments show that it was not necessary to hydrolyze or extract the urine
      prior to assay and that collecting spot urines and normalizing the data to urine
      creatinine gives the same interpretation of the data as total desmosine in a 24
      hour collection. Urine desmosine levels were elevated in 10 of 16 patients with
      CF; however, daily fluctuations were considerable in some subjects, varying as
      much as 5-fold and underlining the importance of assaying several consecutive
      days of urine in acute disorders for an accurate estimate of desmosine excretion.
      The RIA for desmosine is a rapid and sensitive assay that requires no sample
      preparation and could be applied to clinical situations that require large
      numbers of samples.

PMID- 8560092
TI  - Efficacy of D-dimer and total fibrin degradation products evaluation in suspected
      pulmonary embolism.
AB  - Three different assays for fibrin/fibrinogen degradation products (FDP) were
      evaluated in patients with suspected pulmonary embolism (PE) as rapid screening
      tests with the aim of evaluating whether they could be used either as a
      substitute of ventilation/perfusion lung scanning or to supplement scintigraphy
      in patients in whom the scan was inconclusive (low or intermediate probability).
      D-Dimer by enzyme-linked immunosorbent assay (ELISA) and latex and total FDP by
      ELISA were measured prospectively in 85 consecutive patients with suspected PE.
      With a cutoff of 500 ng/ml, D-dimer by ELISA presented a 96% sensitivity and a
      42% specificity, with positive and negative predictive values of 49 and 96%,
      respectively. D-Dimer by latex, also with a cutoff of 500 ng/ml showed a 93%
      sensitivity and 29% specificity, with positive and negative predictive values of
      43 and 89%. For total FDP, with a cutoff of 900 ng/ml, the sensitivity and
      specificity were 96 and 26% respectively, with positive and negative predictive
      values of 42 and 93%. A normal assay may have reduced the necessity of a
      ventilation/perfusion only in 28% patients with D-dimer ELISA, 21% with D-dimer
      latex and 17% with total FDP ELISA and with a possible error of 4, 11 and 7%,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8560093
TI  - Cough reflex threshold in diabetes mellitus with and without autonomic
      neuropathy.
AB  - The cough reflex, a vagus-mediated respiratory protective reflex, was
      investigated in diabetics and healthy controls by establishing a cough reflex
      threshold to increasing concentrations of citric acid aerosol. Diabetics with
      autonomic neuropathy (n = 20), whether overtly symptomatic (n = 5) or evident
      only on certain non-invasive cardiovascular autonomic function tests, were found
      to have significantly (p < 0.05 by chi 2 test) raised cough reflex threshold
      (range 1 to > 100%, median value 50%) in contrast to either the non-neuropathic
      diabetics (n = 20) or normal controls (n = 20; range 1-10%, median value 2%).
      This difference suggests vagal (parasympathetic) denervation of the respiratory
      tract, with possible serious consequences, hitherto little appreciated.

PMID- 8560094
TI  - Inhibition by erythromycin of superoxide anion production by human
      polymorphonuclear leukocytes through the action of cyclic AMP-dependent protein
      kinase.
AB  - The long-term low-dose administration of erythromycin is effective in treating
      chronic inflammatory diseases of the lower respiratory tract. The aim of this
      study was to clarify the mechanism for this therapeutic effect of erythromycin.
      We measured its effect on the production of superoxide anion (O2-) by
      polymorphonuclear leukocytes (PMN) that was induced by N-formyl-methionyl-leucyl
      phenylalanine (fMLP) or by phorbol myristate acetate (PMA). 25 microM
      erythromycin inhibited fMLP-induced O2- production by about 50%, but not PMA
      induced O2- production. Moreover, this inhibition was overcome by adding an
      inhibitor of cyclic AMP-dependent protein kinase (PKA), H-89. The fMLP-induced O2
      production was also inhibited by isoproterenol, a beta-adrenergic agonist, and
      by dibutyryl cyclic AMP, a cell membrane permeating analogue of cyclic AMP. The
      inhibition was also overcome by the addition of H-89. Therefore, the effect of
      erythromycin seemed to be, in part, mediated through the activation of PKA. The
      inhibition by erythromycin of O2- generation by PMN may contribute to the
      beneficial effect of this drug in treating chronic respiratory diseases.

PMID- 8560095
TI  - Chloride transport mechanism in swine tracheal submucosal gland cells.
AB  - To clarify the mechanism for Cl- transport in swine tracheal submucosal gland
      cells, we measured chloride (Cl-) flux by means of a Cl(-)-sensitive fluorophore,
      6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ). An abrupt change of Cl(-)-free bath
      to a Cl(-)-containing (114 mM) solution induced the Cl- influx into the cells at
      a rate of 0.52 mM/s (p < 0.05). Removal of sodium (Na+) and the addition of 0.5
      mM furosemide significantly reduced the rate of gradient-induced Cl- influx to
      0.21 (p < 0.05) and 0.19 mM/s (p < 0.05), respectively. In gland tissue treated
      with 0.1 mM ouabain, the removal of external potassium (K+) in the presence of 5
      mM barium significantly reduced the rate of Cl- influx to 0.21 mM/s (p < 0.05).
      An abrupt change from a Cl(-)-containing bath to a Cl(-)-free solution induced
      the Cl- efflux from the cells at a rate of 0.10 mM/s (p < 0.05). Acetylcholine
      increased the rate of gradient-induced Cl- efflux in a dose-dependent manner to
      0.78 mM/s at 10(-6) M. This effect of acetylcholine was significantly diminished
      by diphenylamine-2-carboxylic acid (DPC, 10(-9) M), a Cl- channel blocker (p <
      0.05). Isoproterenol (10(-5) M) had no effect on the Cl- efflux. These findings
      indicate that a Na-K-Cl co-transporter plays a major role in Cl- entry, and that
      Cl- efflux was activated by cholinergic receptor stimulation, but not by beta
      adrenergic stimulation, via a DPC-inhibitable Cl- channel.

PMID- 8560096
TI  - Probability and characteristics of human immunodeficiency virus infection in male
      Greek military personnel with tuberculosis.
AB  - The probability of an AIDS patient being infected with tuberculosis (TB) has been
      studied in different populations and found to be increased by as much as 500
      times, but the reverse, i.e. the probability of a patient with TB being infected
      with HIV, has not been studied. The aim of this study was to investigate the
      hypothesis of greater HIV seropositivity and altered immune status, as indicated
      by CD4+ T-lymphocyte counts, in TB patients. We prospectively studied 162 males,
      aged 18-30 years, hospitalized for active, proven TB. Serum for HIV antibodies
      was tested twice by ELISA and confirmed by the Western blot technique. The
      control group consisted of 145,000 blood donor volunteers serving in the army,
      aged 18-30 years. The number of CD4+ T lymphocytes was also measured in the
      patients and the control group. We found that the rate of HIV seropositivity in
      TB patients was 2.4% (4 of 162), while it was 0.214% in the control group (p <
      0.0001). Using the Bayes' theorem we found that the probability of a TB patient
      being infected with HIV was 9.1%, approximately 150 times higher than the
      expected rate in the matched control group (p < 0.0001). The number of CD4+ T
      lymphocytes was significantly lower in pulmonary and extrapulmonary TB patients
      than in the control group, taking into account the HIV status (p < 0.001). Our
      results suggest that there is a 150 times greater probability of a TB patient
      being infected with HIV. CD4+ T lymphocytes are significantly lower in all groups
      of TB patients.

PMID- 8560097
TI  - Diffuse interstitial lung disease as an early manifestation of ankylosing
      spondylitis.
AB  - A rare case of ankylosing spondylitis with interstitial pulmonary disease of the
      upper lung field, at an early stage in the disease, is described. The patient, a
      35-year-old asymptomatic woman, was admitted to the hospital due to an abnormal
      chest radiograph that was found during preoperative evaluation for a toxic
      adenoma of the thyroid gland. Her mother and sister were also found to suffer
      from ankylosing spondylitis but without lung involvement. History, physical and
      laboratory examination as well as open lung biopsy excluded other causes of an
      interstitial pulmonary disease. The diagnosis of ankylosing spondylitis was based
      on clinical, radiographic, positive human leukocyte antigen (HLA-B27) and
      histologic findings.

PMID- 8560098
TI  - Bullous emphysema occurring in pulmonary sarcoidosis.
AB  - We describe a rare case of bullous emphysema occurring in a young male with
      sarcoidosis. The patient had progressive pulmonary symptoms over 14 years. Chest
      radiology showed bilateral bullae predominantly of both upper and the left lower
      lobes and mild bronchiectasis. Pulmonary function tests revealed mild restrictive
      disease and a severe reduction in diffusion capacity. Loss of alveolar surface
      area due to bullous disease contributes to functional and physiological
      impairment of lung function in sarcoidosis.

PMID- 8560099
TI  - Invasive thymoma with hypogammaglobulinemia spreading within the bronchial lumen.
AB  - A case of invasive thymoma with hypogammaglobulinemia showing endobronchial
      growth is presented. A 63-year-old man was admitted for evaluation of a left
      hilar mass. A biopsy specimen obtained from the intraluminal mass, which occluded
      the left upper division bronchus, was highly suggestive of thymoma. The
      laboratory tests were almost normal except for hypogammaglobulinemia. The tumor
      was resected with the left upper lobe. Most of the tumor invaded the left upper
      lobe, and grew into the bronchi. The case was diagnosed histologically as
      invasive thymoma spreading within the bronchial lumen.

PMID- 8560100
TI  - Compression characteristics of CPR manikins.
AB  - We evaluated the force-depth compression characteristics of 8 different CPR
      manikins during mechanical cardiopulmonary resuscitation by a thumper. The force
      required to compress the manikin's thorax of 1, 2, 3, 4 and 5 cm was measured. It
      ranged between 6.3 and 14 kp at a depth of 1 cm, 11.6-30 kp at 2 cm, 17-38 kp at
      3 cm, 22.5-54 kp at 4 cm and 28.5-69 kp at 5 cm. The manikins with a spring in
      the thorax (Ambu Man, Ambu MultiMan, Drager CPR-Max, Laerdal Resusci Anne) as
      well as one without (Ambu CPR Pal) showed a rather linear relationship between
      depth and force required to compress the chest. Ambu Man, set at 'High', Laerdal
      Resusci Anne and Drager CPR-Max revealed a slight increase in resistance, whereas
      2 manikins without a spring (Laerdal Little Anne, Laerdal Family Trainer) and 1
      manikin with a plastic spring-like construction (Actar 911) exhibited less
      resistance with increasing depth. According to our results, the manikins are not
      uniform in their compression characteristics; some become nonlinear when 3 cm of
      compression is exceeded. For correct CPR it is of utmost importance that the CPR
      trainee learns to compress in a sufficiently strong manner, but simultaneously to
      avoid an exceedingly high depth of compression irrespective of the thorax
      resistance. In order to prepare the CPR student for the varying chest resistances
      of the human body, we recommend to train CPR on manikins with different chest
      resistances.

PMID- 8560101
TI  - Semi-automatic external defibrillation and implanted cardiac pacemakers:
      understanding the interactions during resuscitation.
AB  - Many emergency medical service (EMS) systems are currently implementing semi
      automatic external defibrillation (AED) by emergency medical technicians.
      Surprisingly little information is available on the possible interactions between
      AEDs and implanted cardiac pacemakers. Therefore, at present there are no clear
      guidelines for the use of AEDs on patients having a cardiac pacemaker. During
      resuscitation, multiple interactions between pacemakers and AEDs are possible.
      External defibrillation can cause damage to several functions of the pacemaker.
      On the other hand, the presence of pacemaker spikes during cardiac arrest might
      prohibit recognition of the ventricular fibrillation by the AED. We report on two
      resuscitation attempts in which the interaction between the ventricular
      fibrillation, an implanted dual chamber pacemaker and the AED was decisive for
      the defibrillation success. A clear understanding of these possible interactions
      is necessary for the further refining of diagnostic algorithms and clinical
      strategies of prehospital defibrillation.

PMID- 8560102
TI  - Predictors of short-term survival after helicopter rescue.
AB  - The purpose of the present retrospective study was to identify easily obtainable
      predictors of short-term outcome for emergency victims treated by a physician
      staffed helicopter emergency medical system (HEMS). The study was conducted at
      the HEMS unit 'Christophorus 1' based at Innsbruck, Austria. Outcomes for 2139
      patients rescued in primary missions during a 3-year period from 1 January 1989
      to 31 December 1991 were included in the study. The majority of missions were in
      response to sports accidents, although missions included a wide spectrum of
      emergencies. Data were obtained from the 'Christophorus 1' operation protocols
      and by written, personal, or telephone request from admitting hospitals. Eleven
      parameters selected from the HEMS flight logs were tested for their predictive
      value on survival following helicopter rescue. In a univariate analysis, the
      cause of the emergency, time at the scene, total duration of the emergency
      mission, patient age, patient gender, severity of the emergency using the
      National Advisory Committee of Aeronautics (NACA) scoring system, state of
      consciousness, respiratory status and patient circulatory status each had a
      statistically significant influence on survival up to 90 days following the
      emergency. Flight time to the scene and the original specialty of the
      additionally trained emergency physician had no significant influence on outcome.
      Multivariate analysis using the Cox proportional hazards model revealed that
      severity of the emergency by the seven-level NACA scale (P = 0.0001), initial
      respiratory status (P = 0.0001), time at the scene (P = 0.0108), patient age (P =
      0.0047) and patient gender (P = 0.0477) were each independent predictors of short
      term survival following physician-staffed helicopter rescue. We conclude that the
      parameters described above can be used in an initial predictive assessment by the
      flight physician and the admitting institution.

PMID- 8560103
TI  - Paediatric out-of-hospital cardiac arrests--epidemiology and outcome.
AB  - OBJECTIVE: To determine the epidemiology and aetiology of out-of-hospital
      paediatric cardiac arrest and the outcome of resuscitation and to apply the
      Utstein template for the paediatric cardiac arrest population. DESIGN:
      Retrospective cohort study. SETTING: A middle-sized urban city (population
      516,000) served by a single emergency medical services (EMS) system. PATIENTS: 79
      consecutive paediatric (age under 16 years) prehospital cardiac arrest patients
      between January 1, 1985 and December 31, 1994. No patient was excluded.
      INTERVENTION: Advanced paediatric life support according to the recommendations
      of American Heart Association. MAIN OUTCOME MEASURES: Survival from cardiac
      arrest to discharge and factors associated with favourable outcome defined as
      alive 1 year after discharge with Bloom category I or II. RESULTS: 79 patients
      had cardiac arrest. The incidence of paediatric out-of-hospital cardiac arrest
      and sudden unexpected out-of-hospital death was 9.8 and 8.9/100,000/inhabitants
      aged under 16, respectively. The mean age was 2.9 years, 72.2% were under 18
      months. SIDS was the leading cause of cardiac arrest followed by trauma, airway
      related cardiac arrest and (near)drowning. Fifty-two patients were considered for
      resuscitation in whom asystole was the most common initial rhythm (78.9%)
      followed by pulseless electrical activity (13.5%) and ventricular fibrillation
      (3.8%). Resuscitation was attempted in 34 patients. The overall survival rate was
      9.6%, for attempted resuscitation 14.7%, for attempted resuscitation when cardiac
      arrest was witnessed 25.0% and for attempted resuscitation with witnessed arrest
      of cardiac origin 0%. Favourable outcome was registered in four of five
      survivors. Factors associated with favourable outcome were collapse in a public
      place, the near-drowning aetiology of arrest, bystander initiated CPR and short
      duration of resuscitation. Multivariate regression analysis showed no factor
      related to favourable outcome, but MICU time interval < 10 min was related with
      survival. Due to the retrospective nature of this study all core times could not
      be obtained. In spite of this, the Utstein template was applicable also in our
      paediatric cardiac arrest population. CONCLUSIONS: Survival from paediatric
      cardiac arrest has remained low. The overall survival rate was 9.6%, survival
      after attempted resuscitation 14.7% and 0% when resuscitation was attempted in
      witnessed arrest of cardiac origin. Asystole was the most common initial rhythm
      and the four leading causes for cardiac arrest were SIDS, trauma, airway related
      arrest and (near)drowning. The Utstein template adopted for adult out-of-hospital
      cardiac arrests was was found applicable also in paediatric cardiac arrests.

PMID- 8560104
TI  - Organizing and implementing a hospital-wide first-responder automated external
      defibrillation program: strengthening the in-hospital chain of survival.
AB  - First-responder automated external defibrillation (AED) in the hospital is
      consistent with the American Heart Association's (AHA) early defibrillation
      standard or care. With trained personnel and automated external defibrillators
      immediately available, early defibrillation should have a greater impact on
      survival than early cardiopulmonary resuscitation (CPR). Therefore, in our
      hospitals we modified basic life support to include automated external
      defibrillation (BLS-AED) for all personnel who are expected to respond to a
      cardiac arrest, with rapid defibrillation taking priority over CPR. We describe
      how we organized and implemented this hospital-wide first-responder BLS-AED
      program. Planning the process includes gaining support from key leaders who are
      responsible for resuscitation practice, and identifying the target audience of
      the training program. Hospital unit needs for AED or conventional defibrillation
      and equipment must be identified, the training program developed, and existing
      policies and procedures modified. Several barriers to implementation may exist.
      Education about the efficacy and safety of AED and experience once the BLS-AED
      program is in place can overcome attitudes and bias. Concerns about the cost of
      equipment and training must be addressed. Program evaluation may include patient
      issues such as measuring the time to the first defibrillation and patient
      outcome; as well as training and retention issues.

PMID- 8560105
TI  - A practical approach to the aetiology of pulseless electrical activity. A simple
      10-step training mnemonic.

PMID- 8560106
TI  - The use of ultrasound in the non-invasive detection of changes in the renal
      circulation in response to blood loss using an animal model.
AB  - Using a continuous haemorrhage model, 8 anaesthetised swine were bled 1 ml/kg per
      min for 30 min. The resistance index (RI) of the main renal artery, interlobar
      and arcuate vessels all significantly increased. Cortical Doppler signals were
      lost in 4 animals at a mean arterial pressure of 26 mmHg. After reinfusion of
      blood and normal saline only the RI of the interlobar vessels was significantly
      different from baseline readings. Ultrasound demonstrated non-invasively changes
      in regional blood flow within the kidney in response to hypovolaemic shock.

PMID- 8560107
TI  - The hemodynamic and arterial blood gas response to asphyxiation: a canine model
      of pulseless electrical activity.
AB  - OBJECTIVE: Asphyxiation is a time-honored animal model for producing pulseless
      electrical activity cardiac arrest. To date, there has not been a detailed
      description of the hemodynamic and arterial blood gas response to asphyxiation in
      a large number of animals. Our objective was to describe a single laboratory's
      experience with a standardized canine model of asphyxial pulseless electrical
      activity arrest. METHOD: Design--Data from 4 separate research protocols using a
      standardized asphyxial model were retrospectively reviewed. Setting-
      Resuscitation research laboratory. Participants--169 mixed-breed dogs.
      Interventions--Each animal was anesthetized and instrumented for hemodynamic
      monitoring. The endotracheal tube was clamped and hemodynamic data was monitored.
      Following loss of aortic fluctuations by thoracic aortic catheter, animals
      remained in pulseless electrical activity for up to 20 min. Hemodynamic data was
      measured continuously and arterial blood gases were sampled intermittently.
      RESULTS: Following endotracheal tube clamping, there was a characteristic
      increase in heart rate and systolic blood pressure. The heart rate peaked at 2-3
      min following clamping, while the systolic blood pressure peaked at 7 min. Both
      heart rate and systolic blood pressure then steadily decreased until loss of
      aortic fluctuations. Loss of aortic fluctuations occurred 11.4 +/- 2.4 min
      following clamping. Following loss of aortic fluctuations, the heart rate
      steadily decreased. Arterial blood gases during asphyxiation and pulseless
      electrical activity arrest showed profound hypoxemia with hypercarbia (pH 7.03 +/
      0.07; Pco2 93 +/- 19; Po2 12 +/- 7 at loss of aortic fluctuation). CONCLUSIONS:
      In this canine asphyxial model of pulseless electrical activity, a characteristic
      hemodynamic pattern of mild tachycardia-hypertension-bradycardia-hypotension was
      produced. Arterial blood gases reflect a profound hypoxemia and respiratory
      acidosis.

PMID- 8560108
TI  - Origins of cardiopulmonary resuscitation. Death, life and resuscitation in
      ancient Greek religion.

PMID- 8560109
TI  - Recommended guidelines for uniform reporting of pediatric advanced life support:
      the Pediatric Utstein Style. A statement for healthcare professionals from a task
      force of the American Academy of Pediatrics, the American Heart Association, and
      the European Resuscitation Council.
AB  - This consensus document is an attempt to provide an organized method of reporting
      pediatric ALS data in out-of-hospital, emergency department, and in-hospital
      settings. For this methodology to gain wide acceptance, the task force encourages
      development of a common data set for both adult and pediatric ALS interventions.
      In addition, every effort should be made to ensure that consistent definitions
      are used in all age groups. As health care changes, we will all be challenged to
      document the effectiveness of what we currently do and show how new interventions
      or methods of treatment improve outcome and/or reduce cost. Only through
      collaborative research will we obtain the necessary data. For these reasons, and
      to improve the quality of care and patient outcomes, it is the hope of the task
      force that clinical researchers will follow the recommendations in this document.
      It is recognized that further refinements of this statement will be needed; these
      recommendations will improve only when researchers, clinicians, and EMS personnel
      use them, work with them, and modify them. Suggestions, recommendations, and
      other comments aimed at improving the reporting of pediatric resuscitation should
      be sent to Arno Zaritsky, MD, Eastern Virginia Medical School, Children's
      Hospital of The King's Daughter, Division of Critical Care Medicine, 601
      Children's Lane, Norfolk, VA 23507.

PMID- 8560110
TI  - [1st sexual intercourse and 1st pregnancy in puerperal women at a hospital of the
      metropolitan area].
AB  - One thousand women hospitalized at a maternity were surveyed after their delivery
      or abortion about their first sexual intercourse and pregnancy. Mean age at the
      first sexual intercourse was 18.7 years and only 9.2% used a contraceptive method
      in spite that 20% were not willing to become pregnant. The mean age of sexual
      partners was 22 years old. Women of less than 32 years old generally had older
      sexual partners, but among those older than 25 years old the proportion of
      younger partners increased. The first pregnancy occurred at 20 years old as a
      mean, 62% of women were single, only 1.3% used a contraceptive method, and 27.3%
      of resultant pregnancies were not desired.

PMID- 8560111
TI  - [Relationship between the duration of the clinical course of human brucellosis
      and the avidity of specific IgG antibodies].
AB  - The aim of this work was to relate the avidity of specific IgG antibodies with
      the time of evolution of human brucella infection. IgG anti-brucella antibodies
      were measured using an ELISA assay with 8 M urea in 17 patients with recent
      active brucellosis (group I), 31 patients with chronic active brucellosis (group
      II) and 120 asymptomatic patients with past brucellosis (group III). Twelve
      patients of group I (70.6%), three of group II (9.7%) and none in group III had
      low avidity antibodies against Brucella. It is concluded that these antibodies
      have a high diagnostic efficiency for recent Brucella infections.

PMID- 8560112
TI  - [Diltiazem versus intravenous nitroglycerin in the treatment of unstable angina
      pectoris. A randomized study].
AB  - Prognosis of unstable angina pectoris is related to admission EKG changes and
      prompt symptom control. The aim of this study was to compare the clinical effects
      of intravenous diltiazem (DTZ) or nitroglycerin (NTG) in patients with unstable
      angina pectoris. We studied 43 patients admitted to the hospital with a history
      of rest angina within the last 48 hours, associated with EKG evidence of
      ischemia. All subjects received intravenous heparin and oral aspirin, 23 were
      randomly assigned to receive intravenous DTZ and 20 to receive intravenous NTG.
      Both groups had similar baseline features and the endpoints of treatment were
      recurrence of angina, myocardial infarction, death during hospitalization and
      secondary side effects. Treatment with DTZ, when compared to NTG, resulted in a
      significant reduction of recurrent angina (8.7 and 59% respectively; p < 0.005),
      number of angina episodes per patient (0.18 +/- 0.5 and 0.9 +/- 1.2 respectively;
      p < 0.05) and lower need for dose increment to control symptoms (3 and 9 patients
      respectively; p < 0.05). The most common side effects observed were cephalea with
      NTG (60% of patients) and asymptomatic sinus bradicardia with DTZ (28% of
      patients). In each group, one patient had a myocardial infarction and one patient
      died. It is concluded that intravenous DTZ reduces myocardial ischemia to a
      greater extent than NTG and can be safely used in patients with unstable angina
      pectoris.

PMID- 8560113
TI  - [Treatment of breast cancer in males].
AB  - Breast cancer is an unusual disease in males. We report the treatment results in
      12 male patients with breast cancer and without distant metastases at the moment
      of diagnosis, treated between 1978 and 1993. All were subjected to surgical
      resection and radiotherapy; chemotherapy was not used. In four patients with
      local lymph node involvement, tamoxifen was used. Clinical staging at the moment
      of diagnosis was stage I in one patient, stage II in seven and stage III in four.
      Subjects were followed for a mean of 67 months and a median of 56 months. Local
      control of the tumour was achieved in 100% of patients and five years survival
      was 90%. Two patients presented with distant metastases at nine and 106 months of
      follow up. It is concluded that breast cancer in men has a similar survival rate
      than in women.

PMID- 8560114
TI  - [Junctional reciprocating tachycardia: clinical and electrophysiological
      characteristics, and the role of fulguration in 5 cases].
AB  - The permanent form is a variety of junctional reciprocating tachycardia that is
      refractory to medical treatment. The anterograde arm of the circuit is formed by
      the His Purkinje bundle and the retrograde conduction is through a slow
      conduction Accessory Atrioventricular Pathway. We report five patients with this
      type of arrhythmia, subjected to electrophysiological assessment. Their mean age
      was 37 years, all suffered from palpitations and several medical treatments had
      failed. During tachycardia, electrocardiogram had a negative P wave in inferior
      leads and RP interval was bigger than PR interval. Accessory Pathway were located
      in the right postero-septal region in three patients, in the left postero-septal
      region in one and in the left lateral in one. Specific bundle fulguration was
      successfully attempted in four patients, in whom arrhythmias did not recur
      without medical treatment.

PMID- 8560115
TI  - [Clinical and anatomopathological study of 5 patients with vasculitis and anti
      neutrophil cytoplasmic antibodies with cytoplasmatic pattern].
AB  - We report five patients with vasculitis and antineutrophil cytoplasmic antibodies
      with cytoplasmatic pattern. All had severe upper and lower respiratory tract
      necrotizing lesions. Three had kidney failure due to rapidly progressive
      glomerulonephritis. The pathological study showed a crescentic
      glomerulonephritis, a chronic granulomatous inflammation in the lungs and in the
      nasal mucosa, an acute nonspecific inflammation or a chronic granulomatous
      inflammation and focal blood vessel fibrinoid necrosis. All patients with
      simultaneous involvement of lungs and kidneys had high titers of antineutrophil
      cytoplasmic antibodies. The nomenclature and classification of these diseases is
      discussed.

PMID- 8560116
TI  - [Microsporidiosis in patients with chronic diarrhea and AIDS, in HIV asymptomatic
      patients and in patients with acute diarrhea].
AB  - Microsporidia are intracellular protozoa that mainly affect AIDS patients and
      chronic diarrhea, caused by the strains Enterocytozoon bieneusi and Septata
      intestinalis, is the most common clinical manifestation. The diagnosis is made in
      intestinal biopsies, however the recently developed trichromic stain with
      chromotrope 2R, is able to detect microsporidia in stools and has a good
      correlation with the biopsy. Using this technique, we studied 43 asymptomatic HIV
      infected subjects, 89 AIDS patients with chronic diarrhea and 186 patients with
      acute diarrhea as controls. Thirty-three percent of patients with AIDS, 16.3% of
      HIV infected subjects and none of the individuals with acute diarrhea had
      microsporidia in their stools (p < 0.05). In 15 patients with AIDS we detected
      intermitted stool microsporidia shedding; this finding should encourage
      repetitive examinations in negative cases. The trichromic stain for microsporidia
      is proposed as a routine test in AIDS patients with diarrhea.

PMID- 8560117
TI  - [Diagnostic role of the combination of computerized tomography and angiography in
      traumatic injuries of the thoracic aorta].
AB  - AIM: To assess the diagnostic value of the combination of computed tomography and
      angiography in patients with blunt thoracic trauma and suspicion of aortic
      injury. PATIENTS AND METHODS: Retrospective analysis of six patients, aged 22 to
      72 years old, with traumatic thoracic aorta injury secondary to severe trauma,
      specially car accidents, seen between 1985 and 1994. RESULTS: An early diagnosis
      was done in three patients. One patient, in whom diagnosis was delayed, died
      before surgery. In three cases, CAT scan showed indirect evidence of aortic
      rupture, consisting in alterations of aortic outline. In other three patients, it
      showed hemomediastinum, associated to a left hemothorax in one case. Angiography
      confirmed the diagnosis, localized and characterized the injury in all patients.
      CONCLUSIONS: The delay in the diagnosis of aortic injury may be fatal. The
      combination of CAT scan and angiography has a high sensitivity and specificity to
      localize and characterize lesions of the aorta or its branches or associated
      organs, essential step for surgical planning. CAT scan restricts the use of
      angiography, avoiding false negative studies, but cannot be used as the sole
      diagnostic procedure.

PMID- 8560118
TI  - [Treatment of ocular inflammatory disease with glucocorticoids and
      cyclophosphamide pulses].
AB  - The effectiveness, toxicity and prognostic factors influencing responses to
      cyclophosphamide (CP) iv pulses plus oral glucocorticosteroids (GC) in patients
      with GC-resistant ocular inflammatory diseases (OID) was evaluated in a cohort of
      15 consecutive patients suffering from active, non-infectious OID refractory to
      oral GC. All patients underwent monthly evaluations with clinical, hematological,
      hepatic, renal and ophthalmologic tests. These included checking visual acuity
      and both anterior chamber and posterior segment inflammation. The overall effect
      evaluated by repeated measurements ANOVA demonstrated that after an average of 5
      CP pulses 1-10, the group showed significant improvement regarding of visual
      acuity and inflammation (p < 0.000001). Amelioration was not sustained over time
      in patients with granulomatous uveitis. Patients with retinal vasculitis
      experienced rapid and sustained recovery. By the end of the follow-up period, 53%
      of the patients had improved, 20% remained stationary and 26% suffered visual
      acuity deterioration as compared with the baseline. No serious side effects were
      detected during treatment and follow-up. CONCLUSIONS: A combination of oral GC
      and iv CP pulses appears to be an effective way to treat patients suffering from
      noninfectious, non-granulomatous, GC-resistant OID.

PMID- 8560119
TI  - [Factitious gastrointestinal hemorrhage in 3 school-age girls].
AB  - Three female patients aged 9, 13 and 14 years, respectively, seen by the authors
      over a 1-year period presented with the complaint of recurrent hematemesis (2
      patients) or melena (1 patient). The (presumed) bleeding episodes had only been
      seen by the respective patient and one parent (the mother in two cases and the
      father in one). In two cases, the other parent was antagonistic with the reported
      situation. A clear symbiosis had been forged between the index case and the
      allied parent. Two patients had previously been seen in several hospitals and had
      undergone various diagnostic tests, including esophagogastroduodenoscopies, all
      of which had proved normal. Two girls had attempted suicide. Two of the mothers
      had a depressive disorder. Re-evaluation of the patients by the authors again
      ruled out any cause for the presumed bleeding or any sequelae originating from
      it. The patients and their parents were referred to a psychiatric service but
      this was only complied by one family; the other two repeatedly avoided attending
      the psychiatric clinic. Awareness of this pattern of presentation and of the
      psychiatric profiles of the patients and their families is critical for
      practitioners in order to recognize factitious illness whenever a patient with a
      history of gastrointestinal bleeding presents with incongruous or illogical
      medical history and clinical findings.

PMID- 8560120
TI  - [Osteopoikilosis. A clinical case].
AB  - We report a 35 years old female presenting with a right wrist pain. Physical
      examination was normal but, on a hand X ray examination, multiple dense para
      articular bone foci were observed. Studying the rest of the skeleton, similar
      alterations were found in pelvis, knees, ankles, feet, shoulders and elbows.
      Osteopoikilosis is an infrequent sclerotic bone dysplasia. Its diagnosis is made
      by the observation of multiple dense, nodular and symmetrical images of para
      articular location on bone X ray examinations. It has no clinical or pathological
      importance. Thus, it must be distinguished from osteoblastic bone metastases.

PMID- 8560121
TI  - [Pharmacokinetic implications associated to the use of drugs as racemates or pure
      enantiomers].
AB  - This article critically reviews the recent specialized literature concerning the
      influence of the stereochemical nature of quiral drugs on the pharmacokinetic
      processes and its pharmacological implications. Evidence is presented indicating
      that as a function of the type of enantiomer administered, profound differences
      in the pharmacokinetic profiles, e.g. absorption, distribution, biotransformation
      and elimination can occur. As a consequence of the enantioselective nature of the
      drug-organism interaction, major differences in the therapeutic responses can be
      envisaged depending on whether the drug is administered as a pure enantiomer or
      as a racemic mixture.

PMID- 8560122
TI  - [Non-university programs for specialist training: an experiment at the National
      Autonomous Corporation for Certification of Medical Specialties (CONACEM)].
AB  - After 10 years certifying medical specialists Conacem is committed to evaluate
      the process focusing, among other aspects, on critical issues of postgraduate
      training programs. In this prospect, it has been important to look at the fact
      that there are several non university programs with a variety of contents,
      institutional sponsorship, curricula and faculty support. This constitutes a very
      inhomogenous source of knowledge and skills, even though many arise in the same
      area of academic influence of the most traditional Medical Schools. Available
      data disclose 316 specialty programs, alluded by 398 physicians, that were
      offered in about 40 institutions, referring to 28 different disciplines. This
      represents the 20.7% of all the specialists certified in this period with
      accomplished formal academic programs. At least 92.7% pertain to institutions
      academically related to the Medical Faculties and, among them, a 77% to the
      University of Chile. This information allows a critical review of proposals and
      to raise initiatives to put in order some scenarios of postgraduate education,
      that urgently need to be better managed from the standpoint of both the
      universities and the accreditation system.

PMID- 8560123
TI  - [The death of Moctezuma II].
AB  - Moctezuma was the Aztec emperor when Spaniards arrived in Mexico in 1519. After
      his entrance in Tenochtitlan, Cortes held the emperor hostage, forcing him to
      govern under conditions in his own palace. The psychic evolution experienced by
      Moctezuma until his death in 1520 is analyzed based on testimonial reports of
      Benal Diaz del Castillo and historian contributions. Although there is evidence
      that Moctezuma was stoned and wounded by an arrow, we propose the hypothesis that
      the emperor was affected by a Major Depression.

PMID- 8560124
TI  - [Prevalence of hepatitis C virus antibodies in pregnant women in Santiago].

PMID- 8560125
TI  - [Which are the causes death among Chilean women?].
AB  - We analyzed all death certificates issued during 1991 to investigate the
      principal diseases causing death among Chilean women. We calculated direct
      relative risks and their confidence intervals, highlighting those diseases
      causing a significantly higher number of deaths among women. The main causes of
      death, shared by men and women, were acute myocardial infarction, cerebrovascular
      diseases and bronchopneumonia. The diseases that caused more deaths among women
      were fractures of head of femur, gallbladder cancer, mitral valve disease, kidney
      infections and cholelithiasis.

PMID- 8560126
TI  - [Nicanor Rojas, dean of the School of Medicine during Balmaceda's dictatorship].
AB  - The Chilean President Jose Manuel Balmaceda (1886-1891) had a constitutional
      conflict with the parliament. This conflict lead to a revolution that ended with
      the President's suicide, when he was refuged at the Argentinian Embassy in
      September 1891. President Balmaceda conducted an authoritarian government during
      several months. A decree from February, 1897, disposed the reorganization of the
      Medical School, dismissed and imprisoned the Dean, Dr Barros-Borgono and
      nominated new Professors. Dr Nicanor Rojas, Professor of Gynecology was assigned
      as Dean and Dr Carlos Sazie as secretary. During the During the war against Peru
      and Bolivia, Dr. Rojas worked gratuitously and became prominent, being named
      Chief Surgeon of the Chilean Army. After the triumph of the revolution against
      President Balmaceda, Dr Rojas was discharged, and died in 1892.

PMID- 8560127
TI  - Chronic alveolar hypoventilation: a review for the clinician.
AB  - Chronic alveolar hypoventilation may present in an insidious fashion with
      nonspecific manifestations. The clinician should be aware of the potential for
      developing this condition in patients with certain thoracic and systemic
      diseases. Once chronic alveolar hypoventilation is confirmed with arterial blood
      gas analysis, a systematic evaluation can often point to the underlying etiology.
      As sleep in affected individuals is often associated with marked worsening of gas
      exchange and may also contribute to worsening daytime cardiopulmonary
      dysfunction, polysomnography is often indicated to determine the severity of
      nocturnal aberrations and to look for coexistent obstructive sleep apnea. Therapy
      of chronic alveolar hypoventilation often focuses on elimination of the nocturnal
      deterioration in gas exchange, and recent applications of noninvasive positive
      pressure ventilation during sleep have proven useful in the management of
      individuals with obesity-hypoventilation syndrome, restrictive thoracic
      disorders, neuromuscular diseases and central causes for hypoventilation. It is
      unclear whether wide-spread application of nocturnal ventilatory support to
      patients with chronic ventilatory failure due to chronic obstructive pulmonary
      disease is of long-term benefit.

PMID- 8560128
TI  - Impact of self-reported sleep-breathing disturbances on psychosocial performance
      in the Swedish Obese Subjects (SOS) Study.
AB  - Patients with severe obesity commonly have obstructive sleep apnea (OSA). In
      order to determine the impact of OSA on psychosocial morbidity in severe obesity,
      subjects enrolled in the Swedish Obese Subjects (SOS) Study were classified into
      two subgroups based on questionnaire data: one group with a high likelihood and
      one with a low likelihood of OSA. These groups were contrasted and multivariable
      analysis was used to examine whether OSA had independent effects on divorce rate,
      sick leave, work performance, income and self-estimated general health after
      adjustment for obesity, fat distribution, alcohol, smoking, medications and
      coexisting medical conditions. A high likelihood of OSA was identified in 338 men
      and 155 women, compared with 216 men and 481 women who had a low likelihood of
      OSA. Men with OSA were identical in age to men without OSA and had slightly
      higher levels of visceral fat (p = 0.01), but were similar in most psychosocial
      variables except self-perceived general health. Women with OSA were identical in
      age and visceral fat mass to women without OSA, but were characterized by a
      higher rate of impaired work performance, sick leave and divorce. When frequent
      sleepiness was used as an additional discriminator between OSA and non-OSA
      groups, marked differences in psychosocial morbidity were observed. Multivariable
      analysis revealed either OSA or frequent sleepiness or both to be independent
      predictors of amount of sick leave, worse self-rated general health, impaired
      work performance and divorce rate. Therefore OSA, measured by self report, is an
      important independent predictor of psychosocial morbidity in subjects with severe
      obesity.

PMID- 8560129
TI  - The effect of temazepam on respiration in elderly insomniacs with mild sleep
      apnea.
AB  - This study evaluated the respiratory effect of temazepam in elderly subjects
      (mean age 65 +/- 3.8 years), with mild sleep apnea. The 15 subjects of this
      report were enrolled in a larger randomized trial comparing pharmacological and
      behavioral treatments for insomnia. Seven subjects received temazepam 15-30
      mg/day either alone or in combination with behavior therapy, and eight subjects
      received placebo or behavior therapy. The mean baseline respiratory disturbance
      index (RDI) was 9.2 +/- 2.8 for the nondrug and 8.8 +/- 5.3 for the temazepam
      group. There were no significant time, group or interaction effects. There was no
      increase in the RDI in elderly subjects with mild respiratory apnea receiving 15
      30 mg of temazepam.

PMID- 8560130
TI  - Subjective estimates of sleep differ from polysomnographic measurements in
      obstructive sleep apnea patients.
AB  - It is well established that, as a group, insomnia patients overestimate sleep
      onset latency (SOL) and underestimate total sleep time (TST) when compared to
      objective polysomnographic (PSG) findings. Whether a similar phenomenon occurs
      with other sleep disorders is not fully established. We compared the PSG sleep of
      84 patients with suspected sleep apnea (SA) to their subjective experience of
      sleep reported on a sleep diary the morning after PSG testing. Both patients with
      SA (SA+) and those without (SA-) tended to overestimate SOL, but the SA+ group (n
      = 50) made larger overestimations (p < 0.02). The SA+ and SA- groups also
      differed in their accuracy at estimating TST, with SA+ patients underestimating
      TST (p < 0.05). These findings support the premise that marked discrepancies
      between subjective and PSG-determined sleep may not be limited to insomnia, but
      present in other sleep disorders as well, and should be appreciated by
      practitioners when obtaining sleep histories.

PMID- 8560131
TI  - The assessment of upper airway patency during apnea using cardiogenic
      oscillations in the airflow signal.
AB  - We investigated the relationship between airway patency and the occurrence of
      cardiogenic related oscillations in the airflow signal during 67 apneas occurring
      in non-rapid eye movement sleep in eight subjects. Spontaneously occurring apneas
      and apneas induced by mechanical ventilation were analyzed. Airway occlusion was
      determined by direct observation of the pharyngeal lumen using fiberoptic
      endoscopy. The presence or absence of cardiogenic oscillations was determined
      from an expanded airflow signal by an investigator blinded to the airway patency.
      Of the total 67 apneas, complete airway occlusion occurred during 51, and the
      airway remained patent throughout in 16. Cardiogenic oscillations were seen
      throughout 39 of the 51 occluded apneas and throughout 9 of the 16 apneas with
      the airway patent. There was no relationship between the occurrence of
      cardiogenic oscillations and airway patency. In addition, in a canine model where
      the upper airway was anatomically isolated, cardiogenic oscillations were evident
      during apneas in pressure signals recorded from the isolated upper airway and in
      airflow signals at the tracheal stoma. We conclude that cardiogenic oscillations
      cannot be used to predict airway patency during apnea.

PMID- 8560132
TI  - Methodological and statistical problems in sleep apnea research: the literature
      on uvulopalatopharyngoplasty.
AB  - A comprehensive review of the literature on the surgical treatment of sleep apnea
      found 37 appropriate papers (total n = 992) on uvulopalatopharyngoplasty (UPPP).
      Methodological and statistical problems in these papers included the following:
      1) There were no randomized studies and few (n = 4) with control groups. 2)
      Median sample size was only 21.5; thus statistical power was low and clinically
      important associations were routinely classified as "not statistically
      significant". 3) Only one paper presented the confidence bounds that might
      distinguish between statistical and clinical significance. 4) Because of short
      follow-up time and infrequent repeat follow-ups, little is known about whether
      UPPP results deteriorate with time. 5) In at least 15 papers, bias caused by
      retrospective designs and nonrandom loss to follow-up raised questions about the
      generalizability of results. 6) Few papers associated polysomnographic data with
      patient-based quality of life measures. 7) Missing data and missing and
      inconsistent definitions were common. 8) Baseline measures were often biased
      because the same assessment was inappropriately but routinely used for both
      screening and baseline. We conclude that because of these and other problems,
      there is much that is needlessly unknown about UPPP. It is the responsibility of
      the research and professional communities to define training, editorial and
      review procedures that will raise the methodological and statistical quality of
      published research.

PMID- 8560133
TI  - Sleep problems of junior high school students in Taipei.
AB  - The objective of this work was to study the relationship between daily sleep time
      and characteristics of students, e.g. grade level, gender, and academic program.
      A sleep habit questionnaire was designed to survey students at two junior high
      schools, one from northern Taipei and the other from southern Taipei. The impact
      of shortened duration of sleep on daily function was also evaluated. A total of
      965 students and their parents were selected randomly in December 1993 for the
      questionnaire study. The response rate was 96.4% (930) for students and 88.6%
      (855) for parents. The self-reported daily sleep time of students declined, and
      daytime sleepiness and moodiness increased in the higher grades. The girls slept
      fewer hours than the boys and did not show an increase in daytime sleepiness.
      Those students not taking the senior high school joint entrance examination slept
      more hours at night and maintained more alertness in the daytime than those who
      were taking the examination. The more academic pressures that adolescents faced,
      the fewer hours they slept. Students not participating in the joint entrance
      examination seemed to show a healthier sleep pattern. Little sleep at night made
      the students feel sleepy in the daytime and tired, drowsy, moody and difficult at
      arising in the morning. The reason why girls slept less than boys needs further
      investigation.

PMID- 8560134
TI  - Sleep and agitation in agitated nursing home residents: an observational study.
AB  - An observational study was conducted to describe the physical and social
      environment of sleep of 16 highly agitated and cognitively impaired nursing home
      residents, and the relationships between manifestations of agitation and sleep.
      Results showed that nursing home residents were more likely to be observed asleep
      when alone, in their own rooms, and between 9 p.m. and 5 a.m. Considerable
      amounts of sleep were also observed during the day. Great individual variation
      was observed in the presence of sleep-related disorders, although a tendency was
      observed for more fragmented sleep during the day hours. Almost all the agitated
      behaviors observed decreased immediately after sleep. Similar to findings of
      objective studies, much individual variation was found in sleep patterns and
      sleep pathology of cognitively impaired and highly agitated nursing home
      residents. Findings suggest that agitation may be exacerbated by fatigue.

PMID- 8560136
TI  - New actigraphic assessment method for periodic leg movements (PLM).
AB  - A new actigraphic method by which periodic leg movements (PLM) can be measured is
      presented. Data acquistion and analysis were brought into line to distinguish
      short-lasting repetive leg movements from random motor restlessness. The
      definition of PLM follows the generally accepted criteria for PLM scoring. Thirty
      restless legs patients, all also suffering from PLM, were investigated three
      times by polysomnography, including tibialis anterior surface electromyography
      and actigraphy. A high correlation (reliability) was found for the number of PLM
      per hour spent in bed between the two methods. Furthermore, the actigraph records
      PLM specifically. An index of random motor restlessness is not sufficient for a
      reliable PLM according. In addition, periodic movements in sleep (PMS) and PLM
      show comparable variability in general. The actigraphic assessment of PLM,
      however, gives a better measure because PMS recordings may result in a
      substantial underestimation of PLM when sleep efficiency is reduced. This method
      is an ambulatory assessment tool that can also be used for screening purposes.

PMID- 8560137
TI  - Long-term follow-up of chronic insomnia.
AB  - In order to assess the long-term outcome of sleep disturbance, 28 well
      characterized patients with psychophysiological insomnia or sleep state
      misperception were given structured interviews 40 months and 64 months after
      initial assessment. Most patients still reported sleep disturbance, albeit with
      some improvement. The number of nights per week of disturbed sleep decreased,
      subjective total sleep time increased, daytime sleepiness declined, there was an
      increase in feeling refreshed in the morning and there was a trend toward
      decreased global complaints of poor sleep. Subjective sleep latency was
      unchanged, and the only parameter that worsened was difficulty falling asleep.
      Only a minority of the patients (18%) were taking prescription hypnotics at
      follow-up, but these patients believed that they were of benefit. There was a
      significant rate of increase in the use of over-the-counter hypnotics at the time
      of the second follow-up, although there was a low rate of satisfaction associated
      with them.

PMID- 8560138
TI  - Determination of observer-rated alpha activity during sleep.
AB  - Patients suffering from chronic fatigue syndrome (CFS) have been described as
      having alpha intrusion into sleep. In a separate study of the relationship
      between depression and CFS, we investigated the sleep of CFS patients. We could
      not detect any observable alpha anomaly in our group of CFS patients. It is
      possible that there is a subgroup of CFS patients in whom no alpha anomaly is
      present. However, the sleep electroencephalogram (EEG) montage used in our study
      was different to that employed by previous researchers. This paper investigates
      the influence of electrode derivations on the outcome of observable alpha
      ratings. We compared simultaneous recordings of sleep EEG using three commonly
      employed montages. Our results indicate that use of the mastoid reference
      (montage 1) results in the highest observer-related alpha. This may suggest that
      data regarding alpha intrusion should always be collected using montage 1.
      However, there is a possibility that the mastoid electrode is not electrically
      silent and is contaminating the data of the referenced channels. The implications
      of these findings are discussed in relation to the validity of alpha intrusion
      measurement of CFS and fibromyalgia.

PMID- 8560135
TI  - L-dopa therapy of uremic and idiopathic restless legs syndrome: a double-blind,
      crossover trial.
AB  - We report the effects of a single bedtime dose of L-dopa 100-200 mg on sleep
      quality, frequency of periodic leg movements (PLM) and daily living in patients
      with idiopathic and uremic restless legs syndrome (RLS). Seventeen patients with
      idiopathic and 11 with uremic (on continuous hemodialysis) RLS were evaluated
      comparatively by polysomnography, actigraphy and subjective ratings in a
      randomized, controlled and double-blind crossover trial with L-dopa and placebo
      for 4 weeks each. Neurophysiologic assessments showed significant reduction of
      the number of periodic leg movements (p = 0.003) and the PLM-index (p = 0.005)
      most pronounced during the first 4 hours of bedtime after L-dopa (p = 0.001).
      Subjective evaluation confirmed improvement of sleep quality (p = 0.002) and
      showed significantly higher quality of life during daytime (p = 0.030) while the
      patients received L-dopa therapy. We conclude that L-dopa 100-200 mg proved to be
      effective in idiopathic RLS and for the first time under controlled conditions in
      uremic RLS without any severe side effects.

PMID- 8560139
TI  - Sleep-related periodic arm movement.

PMID- 8560140
TI  - Availability of home sleep diagnostic systems.

PMID- 8560142
TI  - Bibliography of recent literature in sleep research.

PMID- 8560141
TI  - Assessment of accuracy and analysis time.

PMID- 8560143
TI  - [Professor Alvaro Eduardo de Almeida Magalhaes].

PMID- 8560144
TI  - [INRAD 2000].

PMID- 8560145
TI  - MRI of congenital pituitary insufficiency.
AB  - We compared 1.5 T magnetic resonance (MR) image findings in 193 patients with
      congenital pituitary insufficiency. One hundred and thirty nine of the MR studies
      were obtained in patients who had isolated growth hormone deficiency (GHD). Other
      fifty-four patients had multiple pituitary hormone deficiency (MPHD). On MR
      images, normal anterior and posterior lobes of the pituitary gland can be clearly
      differentiated because the posterior lobe has a characteristic high intensity on
      T1-weighted images. In fifty-four patients, the high-intensity of the posterior
      lobe was not seen, but a similar high signal intensity was observed at the
      proximal stump in fifty-one patients. This high-intensity area is the newly
      formed ectopic posterior lobe, which also secrets anti-diuretic hormone just as
      the posterior lobe would. MR imaging can demonstrate the transection of the
      pituitary stalk and the formation of the ectopic lobe, revealing to be a usefull
      diagnostic tool in the definition of the type of alteration in growth defects of
      endocrine origin.

PMID- 8560146
TI  - [Percutaneous transluminal angioplasty. An efficient alternative in the treatment
      of peripheral obstructive arteriopathy].
AB  - At the present, patients with obstructive vascular disease in the lower
      extremities can be treated with percutaneous procedures without surgery. By what
      is called Interventional Radiology. Three patients with iliac or femoral arterial
      obstructions were treated with Percutaneous Transluminal Angioplasty (PTA). For
      all of them, claudication was the principal symptom and was treated with PTA due
      the failure of regular treatment. The dilatation was performed with high pressure
      balloon. Both technical and clinical results showed success and there were no
      complications.

PMID- 8560147
TI  - [HIV-associated nephropathy].
AB  - AIDS can affect many parenchymal organs but the renal involvement is of vital
      value for patient's prognosis. Sonography can easily analyse most of all renal
      insult even in those patients without symptoms.

PMID- 8560148
TI  - [Hemifacial spasm: study using magnetic resonance angiography].
AB  - Nine patients with "idiopathic" hemifacial spasm were evaluated with cranial
      magnetic resonance imaging and angiography. Alterations of the posterior fossa
      vasculature, possibly related to the facial nerve irritation, were found in 8
      patients (88%). Magnetic resonance angiography is a noninvasive procedure and
      appears to be a sensitive method to evaluate the hemifacial spasm etiology.

PMID- 8560149
TI  - Nonneoplastic, noninflammatory, cerebral intraventricular cysts.
AB  - Currently, nonneoplastic, noninflammatory, cerebral intraventricular cysts can be
      divided into two groups: neuroepithelial (neuroglial) cysts, and the colloid
      cysts. The neuroglial (neuroepithelial) cysts and colloid cysts were considered
      to be derived from the primitive neuroepithelium, but recent immunohistochemical
      investigations suggest an endodermal origin of the colloid cysts. The
      neuroepithelial cysts were divided into the major categories by their size and
      location. Colloid cysts were characterized by its features. Differential
      diagnosis of the intraventricular cysts were presented.

PMID- 8560150
TI  - [Value of magnetic resonance in the assessment of demyelinating diseases].
AB  - The degenerative diseases that primarily commit the myelin (white matter) are
      rare and varied affections. The diagnosis has different levels of difficulty.
      Some of them are bound to enzymatic disturbances of the myelin metabolism and its
      diagnosis is based upon enzymatic, leucocytic or urine measurements. In some it
      is not possible to measure the biochemical alteration, when the diagnosis shall
      be done clinically, particularly in those cases presenting megaloencephaly. The
      MRI proved to be very sensitive on the detection and diagnosis of the white
      matter diseases.

PMID- 8560151
TI  - Principles of magnetic resonance angiography.
AB  - It has been a decade since it was realized that MR could image blood flow. In
      this period of time, the technique of imaging vascular structures has improved
      significantly and has developed into a new area: vascular magnetic resonance
      imaging or magnetic resonance angiography (MRA). MRA is not simply a single new
      MR imaging technique, rather, it consist of an entire family of new pulse
      sequences. Each one of these pulse sequences requires careful consideration for
      optimal visualization of the vascular structures of interest. Recent development
      in MRA produced not only anatomical information but also physiologic data such as
      flow velocity and flow rates. The intent of this review is the summarize the
      basic principles of neuro MRA techniques currently in use. Terms like: time-of
      flight, phase contrast, signal loss in MRA will be discussed.

PMID- 8560152
TI  - Clinical applications of magnetic resonance angiography.
AB  - The development of MRA 2D TOF or 3D TOF and its implementation in extracranial
      and intracranial circulation has defined some clinical applications. However,
      when deciding to use MRA study some intrinsic aspects must be considered about
      the quality that varies from site to site owing to differences in technique, and
      artefactual signal loss, flow variations that can be misdiagnosed. There is no
      question that MRA can provide useful anatomic and physiologic information about
      the cerebral circulation, also as good screening tool for the setting of
      extracranial carotid disease.

PMID- 8560153
TI  - [Facial and cervical manifestations of AIDS].
AB  - The manifestations of the acquired immunodeficiency syndrome (AIDS) are common in
      the head and neck and include opportunistic infections, malignancies and diffuse
      reactive adenopathy. This article reviews the usual and unusual manifestation of
      AIDS affections of the parotid gland, sinonasal and oral cavity, nasopharynx,
      temporal bone and neck as analysed by different methods of imaging, particularly
      by computed tomography.

PMID- 8560154
TI  - Calcification in primary lung non-Hodgkin lymphoma.
AB  - Calcification in lymphoma before treatment or after chemotherapy is extremely
      rare. There have been scarse reports of calcified masses due to Hodgkin and non
      Hodgkin lymphomas, originating in the main lymphatic chains of the mediastinum
      and retroperitoneum. We report a case of primarily extra-nodal (pulmonary) non
      Hodgkin lymphoma with calcification prior to current treatment.

PMID- 8560155
TI  - [Glomus tumors in head and neck: assessment with magnetic resonance].
AB  - Glomus tumors originate from paranglionic tissues. In head and neck, these
      lesions are mainly found near carotid bifurcation, X nerve, jugular bulb or
      middle ear. These tumors have a low growing rate and are hypervascularized. Their
      histology show "nonchromaffin" cells and vascular structures involved by a
      fibrous matrix. MRI, CT and angiography are imaging methods used in glomus tumor.
      The author describe four cases of jugulo-timpanic glomus tumors studied by MRI,
      showing their main findings and the value of this method to detection of these
      lesions.

PMID- 8560156
TI  - [Hepatic chemoembolization for the treatment of carcinoid syndrome].
AB  - Clinical manifestation of carcinoide syndrome are often difficult to control with
      medical treatment and so present a large problem for doctors. In the majority of
      cases, such manifestations are seen in patients with hepatic metastases. In such
      cases the control of the problem can be achieved by local hepatic treatment. A 57
      year old patient with carcinoide syndrome for a year, with extensive hepatic
      tumor from a carcinoide tumor, whose origins were not lokted, had a urinary
      excretion 5-hidroxi-indolacetic = 73 mg in 24 hours, he used cyproheptadin,
      loperamida and metisergida without showing improvement. In light of the failure
      of medical treatment and the impossibility of surgery he was given into hepatic
      chemoembolization (QEH) with lipiodol, doxorrubicin (1.0 mg/Kg) and mitomicin
      (10.0 mg) twice. Clinical control with absolute recovery of "flushing" and
      diarrhea were achieved, a dose of 5-HIAA U (5.5 mg) after the first application.
      Transitory alterations of the aminotransferasis alkaline phosphates and
      leucocytosis. Besides the post embolization syndrome that regressed in 20 days,
      there were no complications recurring after treatment. The period of recovery was
      more than 9 months. We can then conclude that hepatic chemoembolization is an
      efficient treatment to control carcinoid syndrome.

PMID- 8560157
TI  - Towards molecular oncology.
AB  - Oncogene amplification and loss of heterozygosity for tumor suppressor genes have
      been correlated with prognosis in a variety of human tumors. Detection of
      mutations in tumor suppressor genes have been found to serve as risk factor
      determinants in gastrointestinal adenocarcinomas.

PMID- 8560158
TI  - [Actinic lesions: computed tomography features].
AB  - The authors emphasize the importance of knowing, understanding and identifying
      the radiation-induced changes in various body organs by radiologists in order to
      distinguish them from residual or recurrent malignancies. Computed tomography
      enables the evaluation of the effects and complications of the radiation therapy,
      besides other image modalities, and its findings are outlined. The clinical
      correlation, mainly with the time elapsed between the treatment and the
      examination is very important to establish the diagnosis.

PMID- 8560159
TI  - Memorable dates in radiological history.
AB  - The discovery of Xrays was made by Wilhelm C. Roentgen in 1895. To celebrate
      Roentgen's centenary discovery we taken some of the memorable dates in
      radiological history.

PMID- 8560160
TI  - Intranasal levocabastine for the treatment of seasonal allergic rhinitis: a
      multicentre, double-blind, placebo-controlled trial.
AB  - In this international, multicentre, randomized, double-blind, parallel-group,
      placebo-controlled trial 262 patients participated to assess the efficacy and
      tolerability of levocabastine nasal spray in the treatment of seasonal allergic
      rhinitis. Patients were randomized to receive either twice daily 0.05%
      levocabastine or matching placebo nasal spray with a treatment duration of four
      weeks. Assessments of global therapeutic efficacy favoured levocabastine. At the
      end of the trial, 55% of levocabastine-treated patients considered therapeutic
      efficacy to be excellent or good compared to 36% of those who received placebo (p
      < 0.001). The corresponding values for the investigator assessments were 54% and
      37% (p < 0.001), respectively. Analysis of patients' diary data showed
      significantly lower AUCs for all parameters in the levocabastine group (p <
      0.05). Investigator assessments revealed a trend towards a greater reduction in
      individual symptom severity from baseline in levocabastine-treated patients
      compared to placebo-treated controls. Adverse experiences were reported by 21% of
      levocabastine-treated patients and by 19% of those who received placebo, with no
      statistically significant differences in incidence or type. Headache and local
      reactions following application were the most frequently reported adverse events.
      Levocabastine nasal spray appears to be effective and well-tolerated for the
      treatment of seasonal allergic rhinitis and is an alternative to oral
      antihistamines.

PMID- 8560161
TI  - Intranasal immunotherapy with Dermatophagoides extract: in vivo and in vitro
      results of a double-blind placebo-controlled trial.
AB  - Intranasal immunotherapy (IT) has been proposed as a means to induce an effective
      immunity of the nasal mucosa in patients with allergic rhinitis, avoiding
      systemic side effects. In the present study 20 individuals with chronic allergic
      rhinitis, and skin prick test reactive to Dermatophagoides pteronyssinus (DP)
      only, were randomized and subjected to a three months' double-blind placebo
      controlled trial of intranasal IT with DP extract. All patients received also
      sodium cromoglycate as pre-medication. Before and at the end of the treatment the
      patients performed specific nasal provocation tests, and samples of serum and
      nasal secretions were collected to measure total and specific IgE, levels of
      eosinophil cationic protein (ECP), and mast-cell-derived tryptase. A clinical
      score was computed by the symptoms indicated by the patients. The clinical score
      did not change in the two groups after the treatment, whereas a decrease in nasal
      reactivity was observed. Total IgE increased only in secretions from placebo
      treated patients, but were not modified in sera. IgE to DP in sera and nasal
      secretions did not change significantly. Tryptase levels in nasal secretions
      decreased in both groups, while ECP was unchanged after IT. Serum ECP levels
      decreased more in actively treated patients than in the placebo group. The data
      suggest that changes of IgE and inflammatory mediators may be affected by the use
      of sodium cromoglycate in both groups, but some parameters change early in
      different directions in IT- and placebo-treated groups.

PMID- 8560162
TI  - Clinical efficacy of N-acetyl-aspartyl-glutamic acid nasal spray in children
      suffering from pollinosis: a double-blind multicentre study.
AB  - A double-blind, four-centre study was carried out in 66 children to compare the
      clinical efficacy and safety of N-acetyl-aspartyl-glutamic acid (NAAGA) and
      disodium cromoglycate (DSCG) nasal sprays. At similar dosage conditions (one puff
      per nostril, four times daily, for 3 weeks), no significant differences between
      the treatments were discernible in the primary efficacy parameters (scores,
      patients' and physicians' opinion). Both products induced statistically
      significant improvements in the nasal, ocular and total scores, but not in the
      respiratory (breathing) score. The hay-fever symptoms improved clinically in >
      50% of the children after only two weeks with both treatments. The exact figures
      depended on the parameters considered. Thirteen out of 25 patients (52%) in the
      NAAGA group found the efficacy "good" or "excellent" at the end of the treatment
      period; the corresponding opinion in the DSCG group was expressed by 10 out of 24
      patients (41.7%). Of the 28 patients that used the rescue medication, 12 (42.8%)
      were from the NAAGA group and 16 (57.1%) from the DSCG group. One patient on
      NAAGA treatment reported side effects, i.e. pruritus in the nose and sneezing.

PMID- 8560163
TI  - The interdomal ligament does not exist.
AB  - Some authors consider the interdomal ligament to be an important structure of
      nasal tip support, whereas in other studies of lobular anatomy such a ligament is
      not mentioned at all. To clarify this question, we performed an anatomical
      investigation, which included macroscopical dissection and histological
      sectioning of 14 human cadaveric noses. Our anatomical study failed to reveal the
      presence of an actual ligament in the interdomal area.

PMID- 8560164
TI  - Errors arising in cross-sectional area estimation by acoustic rhinometry produced
      by breathing during measurement.
AB  - Standardization of acoustic rhinometry is becoming increasingly important as the
      use of this technique becomes more widespread. The effects of breathing through
      the nose during acoustic rhinometry were investigated to determine if this
      affected the measurements of minimal cross-sectional area. During inspiration,
      and inspiration with the contralateral nasal airway obstructed, the minimal cross
      sectional area decreased by 12.48% (p < 0.05) and 56.68% (p < 0.01),
      respectively, from the measurement made during a breathing pause. During
      expiration the reverse was observed, with increases in the minimal cross
      sectional area of 13.95% (p > 0.05) and 40.20% (p < 0.05), respectively. In all
      but quiet expiration, the minimum cross-sectional area recorded during
      respiratory manoevres, differed significantly from those measured during a
      breathing pause. We recommend that in order to avoid changes in nasal
      measurements during breathing, acoustic rhinometry should be performed during a
      brief breathing pause.

PMID- 8560165
TI  - Evaluation of leukocyte chemotactic function in patients with chronic sinusitis.
AB  - In this study the chemotactic activities of neutrophils and monocytes were
      evaluated in patients with chronic sinusitis as compared to a control group.
      Leukocyte chemotaxis was measured with a micropore filter method in blood samples
      taken from 26 patients with chronic sinusitis and 10 volunteers. A statistically
      significant impairment of leukocyte chemotaxis capacity in patients with chronic
      sinusitis was found. It is concluded that a functional disorder of leukocytes may
      play a role in the progression of the disease into a chronic state.

PMID- 8560166
TI  - The effect of a new ostium and sinus mucosal flaps on mucociliary flow of the
      maxillary sinus.
AB  - To evaluate the effect of a new ostium upon the mucociliary flow of the maxillary
      sinus, a window in the lateral wall of the sinuses was made and left open in New
      Zealand rabbits. The contralateral sinuses were used as controls. No change in
      mucociliary flow was observed, except for a shorter clearance time in sinuses
      with a new ostium. In the second group of rabbits the maxillary sinus mucosa was
      elevated at the floor, lateral and medial walls and rotated about 80-90 degrees.
      The other side acted as control, the mucosa was elevated and put in place again.
      The mucociliary flow of sinuses with rotation decreased significantly.

PMID- 8560167
TI  - Endoscopic sinus surgery for nasal polyps in children: results.
AB  - Functional endoscopic sinus surgery (FESS) was performed on 21 children with
      nasal polyps, who had a total of 34 operations, on 65 sides. Retrospectively, we
      reviewed the pre-operative symptoms, pre-operative findings and results of FESS.
      The diagnoses were made with anterior rhinoscopy and CT scan. Allergy could be
      confirmed in 24%. Half of the children (52%) had been previously operated on
      because of nasal polyps. They had more recurrences and worse results than
      children who underwent primary FESS. The subjective results were good in 77% with
      a mean follow-up of more than two years. However, a poor correlation between
      subjective and objective results was noted. Minor complications were seen in 9.2%
      of 65 sides operated on. The specific advantages of FESS in children are
      discussed.

PMID- 8560168
TI  - Endoscopic and CT-scan evaluation of rhinosinusitis in cystic fibrosis.
AB  - In order to obtain an accurate evaluation of nasal and paranasal sinus disease in
      cystic fibrosis patients, 75 patients with a proven cystic fibrosis diagnosis
      have been investigated using the following standard techniques: questionnaire,
      ENT examination, endoscopical examination, sinus X-rays, and in 31% of the cases
      a CT scan. The analysis of results shows that nasal obstruction is the most
      frequent symptom (32%) and that nasal polyps are present in 43% of the cases.
      Endoscopic examination seems to be of great interest in giving a more accurate
      picture of nasal and paranasal sinus disease. Analysis of CT scan images leads
      the authors to describe a new and specific entity in nasal and paranasal sinus
      disease in cystic fibrosis patients: the pseudomucocele. In this report, the
      authors discuss the various aspects of pseudomucocele, attaching particular
      importance to the CT scan results.

PMID- 8560169
TI  - The endoscopic management of sphenoid and ethmoid mucoceles with orbital and
      intranasal extension.
AB  - Mucoceles of the sphenoidal and ethmoidal sinuses act as benign neoplasms and can
      result in bony erosion extending from within the confines of the sinuses into the
      intracranial and orbital spaces. Endoscopic management of such mucoceles has been
      debated, and, by some, considered a radical form of therapy. A review of
      consecutive patients with sinus mucoceles revealed eight sphenoid and six ethmoid
      mucoceles. Four of these were confined to the sinuses and 11 extended outside of
      the confines of the sinuses. There were four with intracranial extension, two
      with orbital extension, three with both intracranial and orbital extension, and
      two involving the clivus. All 15 patients were managed with endoscopic
      decompression. Two patients with ethmoid-frontal mucoceles also had frontal sinus
      obliteration, via an osteoplastic flap along with sphenoethmoidal decompression
      with an endoscopic approach. Thirteen patients had more than one year of follow
      up. Two patients with ethmoid mucoceles with intracranial extension had
      recurrences of the mucoceles which again have been decompressed endoscopically.
      There were no orbital or intracranial complications in relationship to these
      procedures or from the mucoceles. Symptoms related to the mucoceles including
      loss of vision and severe headaches were resolved with decompression. The
      endoscopic management of sphenoid and ethmoid mucoceles with orbital and
      intracranial extension is a safe and reliable approach, obviates the need for
      major intracranial surgery and diminishes post-operative morbidity. Close follow
      up is necessary and secondary decompression can be accomplished should the
      mucocele recur.

PMID- 8560170
TI  - Efficacy of systemic corticosteroid treatment for anosmia with nasal and
      paranasal sinus disease.
AB  - Systemic administration of corticosteroids was attempted in the treatment of
      olfactory loss resistant to topical corticosteroid treatment in patients with
      nasal and paranasal disease and post-upper respiratory infection. Significant
      efficacy was achieved with a short course of high-dose oral corticosteroids in
      patients with non-allergic sinus disease. On the other hand, anosmia induced by
      upper respiratory infection failed to respond to systemic corticosteroid
      treatment, suggesting permanent damage to the olfactory receptor cell. The
      underlying mechanism of effectiveness observed in patients with sinus disease may
      be explained by improvement of the mucosal thickening of the olfactory fissure,
      leading to the access of an odorant to the olfactory neuroepithelium.

PMID- 8560171
TI  - Evaluation of endoscopic sinus surgery for chronic sinusitis: post-operative
      erythromycin therapy.
AB  - We discuss the results of endoscopic endonasal sinus surgery for chronic pan
      sinusitis characterized by nasal polyposis, especially the effects of post
      operative long-term administration of low-dose erythromycin (EM) therapy. The
      subjects analysed in this retrospective study are surgical cases who had
      initially been operated for chronic pan-sinusitis. They are classified into one
      group who has received a post-operative long-term, low-dose EM regimen and into
      another group who has not received this treatment. The groups have been compared
      with respect to: (1) the degree of improvement in the post-operative subjective
      symptoms; (2) postoperative objective findings of the ethmoidal sinus and the
      ostium of the frontal sinus; and (3) the degree of improvement in the maxillary
      sinus lesion. Better improvement is achieved in subjective symptoms and objective
      findings in the EM group than in the non-EM group.

PMID- 8560172
TI  - Nasal obstruction and skull base development: experimental study in the rat.
AB  - The influence of nasal obstruction on the development of the anterior skull base,
      of the tympanic bulla, and of the Eustachian tube was investigated in three
      groups of 20 albino Wistar rats in which one (group B) or both nostrils (group C)
      had been experimentally obstructed by means of synthetic resin mixed with
      radiopaque material. After two months, a cephalometric investigation demonstrated
      that the angle formed by the median line passing through the superior
      interincisive point and the most posterior median point of the occipital bone and
      by the line connecting the tympanic bulla and the superior interincisive point
      was significantly increased when the homolateral nostril had been obstructed if
      compared to controls (group A). On the basis of these preliminary cephalometric
      observations we suggest that nasal obstruction is able to determine anatomical
      changes of the superior maxilla, the skull base, and the jaw, with abnormal
      skeletal growth and consequent possible Eustachian tube dysfunction.

PMID- 8560173
TI  - "Cross-stealing" technique for septal perforation closure.
AB  - The authors described a technique for the surgical repair of anterior septal
      perforations of medium size (up to 2 cm). This technique is based on two
      mucoperichondral (mucoperiosteal) flaps, one from each side of the septum. Four
      patients have been treated in this way, resulting in permanent and complete
      closure in three of them. In one patient the perforation has been significantly
      reduced and positioned much more posteriorly. The main advantage of this
      technique is a mutual overlapping of the raw flap surfaces which prevents drying
      out and decay of the flaps. This technique proves to be rather simple to perform
      and has not shown any evidence of disturbed nasal physiology in a long-term
      follow-up period.

PMID- 8560174
TI  - Acinic cell tumour of the maxillary sinus: an unusual case initially diagnosed as
      parotid cancer.
AB  - An unusual case of acinic cell tumour of the maxillary sinus is presented. The
      patient, a 41-year-old male who had undergone incomplete excision of the tumour
      in the left parotid region previously, was referred to our department for further
      treatment. The initial pathological diagnosis was adenocarcinoma of the parotid
      gland. CT-scan not only revealed tumours in the left pre-auricular and upper neck
      region, but also an enhanced mass in the left maxillary sinus. Although there
      were neither nasal symptoms nor destruction of the maxillary bone, aspiration
      biopsy of the maxillary sinus revealed class V. Total maxillectomy, radiotherapy
      and systemic chemotherapy were performed just after total parotidectomy and
      radical neck dissection at the left side. The clinical and histopathological
      findings are discussed.

PMID- 8560176
TI  - Speaking from experience: ALS patients can lead happy lives.

PMID- 8560177
TI  - Coordinating special projects.

PMID- 8560178
TI  - Minimize the risk of DVT.

PMID- 8560175
TI  - Hutchinson's sign and its importance in rhinology.
AB  - Herpes zoster ophthalmicus usually has a typical appearance. However, if the
      disease is limited to the nasociliary branch of the trigeminal nerve, the ocular
      appearance may be confusing. Hutchinson in 1865 first noted that involvement of
      the external nasal branch of the fifth cranial nerve was associated with an
      increased incidence of ocular zoster. A case of herpes zoster ophthalmicus is
      presented that clinically resembled an ocular complication of sinus disease. The
      presence of a localized vesicular rash at the nasal tip assisted in an early
      diagnosis. Although this sign is known amongst ophthalmologists, its importance
      in rhinology is stressed. An anatomical explanation of Hutchinson's sign is given
      and the treatment of herpes zoster ophthalmicus is briefly discussed.

PMID- 8560179
TI  - Hypokalemia.

PMID- 8560180
TI  - Finally, an ICU flow sheet that makes sense.

PMID- 8560181
TI  - The RN pin collection: symbols of pride.

PMID- 8560182
TI  - Chest tubes made easy.

PMID- 8560183
TI  - Medication errors: learn from your colleagues' mistakes.

PMID- 8560184
TI  - Theophylline is off the OTC market. Ephedrine may be next.

PMID- 8560185
TI  - How about a little respect?

PMID- 8560186
TI  - Another solution to counteract hypoglycemia.

PMID- 8560187
TI  - The two-signal model and 'self'-reactivity: are they really compatible? A reply
      to Faro & Carneiro.
AB  - Given that the associative recognition of antigen (two signal) model permits a
      certain level of 'autoreactivity', Faro & Carneiro argue that this unavoidable
      'autoreactivity' is required as part of the regulation of the general physiology
      of the animal. This paper gives the author's reply pointing out two facets of the
      functioning of the immune system. (1) Under an associative recognition of antigen
      model, the scenarios of B-cell activation postulated by them are ruled out. (2)
      There is no way to use a destructive ridding effector function to regulate the
      self/non-self discrimination because autoimmune reactivity would accompany any
      postulated regulatory mechanism.

PMID- 8560189
TI  - Limited T-cell receptor V gene usage in inclusion body myositis.
AB  - Inclusion body myositis (IBM) is a chronic, progressive inflammatory myopathy.
      The inflammatory infiltrates are dominated by T cells, which frequently invade
      muscle fibres. The present study was performed to characterize the usage of the
      variable (V) segment of the T-cell receptor of muscle infiltrating cells in IBM.
      Using the reverse transcriptase polymerase chain reaction (RT-PCR) technique the
      authors analysed the expression of 22 V alpha and 24 V beta families in muscle
      tissue from six patients with IBM displaying intense inflammatory cell
      infiltration. The following V alpha/V beta families appeared in at least 50% of
      the patients: V alpha 1, 5, 7, 15, 16, 17, 20, 21, 22 and V beta 3, 5.2, 8, 12,
      14, 22. In all patients V alpha 7, 16 and V beta 8 were expressed in muscle
      tissue. Furthermore, in two of the patients peripheral blood lymphocytes (PBL)
      were investigated in parallel. There was a restricted usage of V alpha and V beta
      families in muscle in comparison to PBL, indicating a selective homing or local
      proliferation of T lymphocytes in the inflammatory lesions in IBM.

PMID- 8560188
TI  - HLA-B27-restricted cytotoxic T lymphocyte responses to arthritogenic
      enterobacteria or self-antigens are dominated by closely related TCRBV gene
      segments. A study in patients with reactive arthritis.
AB  - Identification of the T-cell receptors (TCR) used by synovial cytotoxic T
      lymphocytes (CTL) of patients with reactive arthritis (ReA) may be crucial to
      better understanding the pathogenetic mechanism underlying the HLA-B27
      association of spondylarthropathies. The authors, therefore, sequenced 25 TCRB
      chains from HLA-B27-restricted CD8+ CTL clones and two clonal lines specific for
      self- or Yersinia enterocolitica antigen isolated from synovial fluids of 3 HLA
      B27+ patients with ReA and PBL of one healthy HLA-B27+ individual. Fourteen non
      HLA-B27-restricted CTL served as controls. Both autoreactive and Y.
      enterocolitica specific HLA-B27-restricted CTL used a highly limited set of VB
      genes with preferential rearrangement of three closely related VB families (VB
      13, 14, 17), suggesting that these families contain a preferred site for contact
      with the HLA-B27 molecule. In addition, the presence of limited TCRBJ usage,
      limited heterogeneity in CDR3 sequences and dominant clones from individual
      donors among these CTL indicate that TCRB chain usage is further restricted by a
      limited set of peptides bound to the HLA-B27 molecule. Limited TCR usage by SF
      CTL of ReA patients may lay a basis for therapeutical manipulation of the T-cell
      response in the spondylarthropathies.

PMID- 8560192
TI  - Antibody-dependent cellular cytotoxic activity of cells in the rat metrial gland
      in pregnancy.
AB  - Antibody-dependent cellular cytotoxic (ADCC) activity of cells in rat metrial
      glands at days 13 and 20 of pregnancy has been examined. A 51chromium-release
      cytotoxicity assay was carried out using Yac-1 cells and P815 cells as targets in
      the presence of the corresponding, heat inactivated rat antibody or non-immune
      rat serum. No killing was observed when effector metrial gland cells and target
      cells were cultured in the presence of non-immune rat serum. In the presence of
      rat antibody to Yac-1 cells, or rat antibody to P815 cells, cells from the
      metrial glands of rats killed at day 13 of pregnancy demonstrated ADCC activity,
      but cells from the metrial glands of rats killed at day 20 of pregnancy showed no
      ADCC activity. Spleen and peritoneal exudate cells displayed ADCC activity.
      Immunohistological and immunocytological studies showed OX-6, OX-34, OX-35 and OX
      42 positive cells were present at days 13 and 20 of pregnancy, in sections of
      metrial glands and in the cell suspensions prepared for the cytotoxicity assays.
      It is suggested that macrophages are the cells most likely to be responsible for
      the ADCC activity in the rat metrial gland.

PMID- 8560190
TI  - Serum antibodies from patients with primary Sjogren's syndrome and systemic lupus
      erythematosus recognize multiple epitopes on the La(SS-B) autoantigen resembling
      viral protein sequences.
AB  - The aim of this study was to investigate the epitope recognition pattern of La(SS
      B) autoantibodies in sera from patients with Sjogren's syndrome (SS) and systemic
      lupus erythematosus (SLE) using overlapping synthetic decapeptides on solid
      phase. Eighty different decapeptides with five amino acids overlap from the human
      La(SS-B) autoantigen were synthesized on cellulose paper using F-moc chemistry.
      Tests were performed with 14 SS and six SLE sera. The results showed that the
      immune response to the La(SS-B) oligopeptides was restricted and unique for each
      individual with no particular pattern typical for each of the two diseases, apart
      from the fact that SLE sera gave positive reaction with fewer peptides. Regions
      within the N- and C-termini harboured most of the positive sequences. The authors
      specifically addressed the possibility of a viral aetiology for disease
      development or autoantibody generation. In this context the most frequently
      recognized linear epitopes on the La(SS-B) autoantigen showed sequence
      similarities with proteins from a range of ubiquitous human viruses, in
      particular from the herpes virus group. The La(SS-B) autoantibodies may thus be
      generated through molecular mimicry.

PMID- 8560191
TI  - Interleukin 10 release during endotoxaemia in chimpanzees: role of platelet
      activating factor and interleukin 6.
AB  - Interleukin (IL-)10 has been demonstrated to inhibit endotoxin-induced production
      of a number of pro-inflammatory cytokines. The present study sought to compare
      the appearances in the circulation of IL-10, IL-6 and IL-8, and to assess the
      roles of endogenously produced platelet-activating factor (PAF) and IL-6 in IL-10
      release during endotoxaemia in chimpanzees. Intravenous injection of endotoxin
      (lot EC-5, 4 ng/kg, n = 8) induced a transient rise in serum IL-10
      concentrations, peaking after 2 h (213 +/- 70 pg/ml; P < 0.05). No correlations
      existed between peak IL-10 levels, and peak IL-6 and IL-8 levels. Neither
      infusion of the specific PAF antagonist TCV-309 (n = 4), nor infusion of a
      neutralizing anti-IL-6 monoclonal antibody (n = 4) influenced endotoxin-induced
      IL-10 release. IL-10 release elicited by injection of endotoxin is not mediated
      by PAF or IL6.

PMID- 8560193
TI  - The influence of follicular dendritic cells on B-cell proliferation depends on
      the activation of B cells and the mitogen used.
AB  - Follicular dendritic cells (FDC) are unique non-lymphoid cells found only in
      lymph follicles. They play a part in the survival, proliferation and
      differentiation of B cells. To analyse the influence of FDC on B-lymphocyte
      proliferation, we isolated them from human tonsils on albumin gradients and
      treated them with mitomycin C to prevent the multiplication of lymphoid cells
      harboured in their cytoplasmic evaginations. FDC cultured for 12-16 h remained
      attached to the substrate; non-adherent cells were carefully eliminated by
      washing. Purified B cells cultured alone or with contaminant-cleared FDC were
      maintained for 2 days in the presence or absence of various stimulants, after
      which tritiated thymidine uptake by these cells was measured. In the absence of
      activators, FDC did not induce B-cell multiplication. B cells cultured in the
      presence of FDC exhibited increased 3H-TdR uptake when activated with anti-CD40
      MoAb, anti-immunoglobulin MoAb or transferrin, but not when stimulated with
      Staphylococcus aureus strain Cowan I (SAC) at a given concentration. In the
      latter case, B-cell proliferation clearly decreased. In control cocultures where
      mitomycin-C-treated non-adherent cells were used instead of FDC in the presence
      of the different stimulants, no increase in B-cell proliferation was observed.
      The results suggest that, inside the germinal centres, FDC modulation of B-cell
      proliferation depends on the activation state of the B cells and on the stimulant
      encountered.

PMID- 8560194
TI  - Fc gamma receptor expression on sheep afferent lymph dendritic cells and rapid
      modulation of cell surface phenotype following Fc gamma receptor engagement in
      vitro and in vivo.
AB  - Afferent lymph dendritic cells were analysed for the presence of Fc gamma
      receptors by Western blotting and for modulation of surface markers following Fc
      gamma receptor engagement in vitro and in vivo. The results showed that
      unstimulated dendritic cells expressed Fc gamma RII constitutively. When
      dendritic cells were incubated in vitro with antigen/antibody complexes in
      antibody excess, a marked reduction in surface staining was observed for MHC
      class II, CD1, CD44, and VLA-4 after 8 h in culture. These changes did not occur
      with antigen or antibody alone. DC expression of LFA-1 and LFA-3 were slightly
      reduced after 8 h in culture with Ova alone, but this was enhanced slightly when
      the cells were cultured with immune complexes. Even more marked reductions in
      surface staining for MHC class II, CD1, CD44 and VLA-4 were observed on dendritic
      cells 4-8 h following secondary antigen challenge in vivo. LFA-1 and LFA-3
      expression was reduced only slightly. The level of expression of MHC class II,
      CD1, LFA-1 and LFA-3 was substantially increased over resting values 24 h after
      Fc gamma R occupancy. The intensity of staining at this time was also
      significantly elevated for CD44, LFA-1, LFA-3 and VLA-4. These results show that
      engagement of Fc gamma receptors cause a substantial modulation of the dendritic
      cell surface phenotype after immune complex uptake. The phenomenon may function
      to maximize subsequent presentation of the challenge antigen to T cells.

PMID- 8560195
TI  - Expression of MHC class II molecules on human monocytes is regulated
      independently from each other after phagocytosis of bacteria.
AB  - Reactive arthritis is usually self-limiting polyarthritis which develops in HLA
      B27 positive individuals after certain gastrointestinal or urogenital infections.
      The pathogenesis of reactive arthritis is unknown but T cells seem to have a
      crucial role. Most of the antigen-specific T cells isolated from the synovial
      fluid have been MHC class II restricted. The role of antigen presentation in the
      pathogenesis of reactive arthritis has been studied relatively little. In this
      work the authors studied the effect of arthritis-triggering bacterium (Yersinia
      enterocolitica O:3) on the expression of MHC class II molecules on human
      monocytes and found that the expression of different MHC class II molecules was
      regulated independently from each other in half of the individuals after certain
      incubation periods. In these cases the expression of HLA-DP was parallel to the
      expression of HLA-DQ, while HLA-DR expression went to the opposite direction or
      did not change at all. No difference between HLA-B27 negative and HLA-B27
      positive healthy individuals was seen. The authors conclude that independent
      regulation of the expression of different MHC class II antigens on antigen
      presenting cells is a more common phenomenon than usually thought.

PMID- 8560196
TI  - Acquisition of CD40 expression during murine B-cell differentiation.
AB  - Expression of CD40 on mouse cells was investigated comparing the binding to cells
      of a monoclonal antibody against CD40, to that of a soluble fusion protein
      consisting of the extracellular domains of the mouse CD40-ligand. The analysis of
      a series of established cell lines failed to demonstrate expression of CD40 on
      pro- or pre-B cells, and indicated that CD40 expression was restricted to cells
      that had undergone productive heavy- and light-chain gene rearrangements, and
      expressed surface Ig. In cells from normal mice, CD40 first becomes detectable,
      although at low levels, on a subset of small pre-B-II cells in bone marrow, the
      levels of CD40 expression increasing thereafter during B-cell maturation. Thus,
      immature B cells (IgM+ IgDlo B220lo) express intermediate levels of CD40, and
      mature B cells (IgM+ IgDhi B220hi) express high levels of CD40. Anatomical
      location also seems to correlate with the levels of CD40 expression, as B cells
      expressing the highest levels of CD40 were found in lymph nodes and Peyer's
      patches.

PMID- 8560197
TI  - Oral tolerization leads to active suppression and bystander tolerance in adult
      rats while anergy dominates in young rats.
AB  - Oral tolerance was induced in 4-week-old (young) and 12-week-old (adult) rats by
      feeding ovalbumin (OvA)-containing pellets during 4 weeks. Seven weeks after
      removal of the OvA-pellets the rats were immunized with a mixture of OvA and
      human serum albumin (HSA) in Freund's complete adjuvant (FCA), and the following
      immune response was monitored. Both the young and adult groups of OvA-fed rats
      had significantly suppressed OvA-specific delayed-type hypersensitivity (DTH)
      responses and T-cell proliferation, reflecting a long-lasting T-cell tolerance to
      OvA both in vivo and in vitro. Furthermore, spleen cells from rats tolerized as
      adults were able to suppress the proliferation of primed T-cells from normal
      immunized rats, demonstrating the presence of antigen-specific suppressive cells.
      Accordingly, the adult rats showed bystander suppression of the response to HSA
      with respect to DTH-reaction, specific proliferation, and reduced enlargement of
      the draining lymph nodes after immunization. There was no evidence of active
      suppression in vitro or bystander tolerance in the orally tolerized young group,
      indicating that anergy rather than active suppression was prevalent in these
      rats. Furthermore, in the young group there was no suppression of the antibody
      response since the IgG and IgE anti-OvA antibody levels were indistinguishable
      from those of the controls. Contrary to the young rats, the adult fed group
      showed transiently elevated levels of IgG anti-OvA antibodies at 1 week post
      immunization, followed by a subsequent significantly suppressed IgG antibody
      response. In conclusion, the results demonstrate that the induction of anergy or
      active suppression after antigen feeding can be determined by the age at which
      the antigen is introduced to the mucosal immune system.

PMID- 8560198
TI  - Effect of 12 neutralizing anti-cytokine antibodies on in vitro activation of B
      cells. Interleukin-12 is required by B1a but not B2 cells.
AB  - Normal human peripheral blood mononuclear cells, depleted of most monocytes and
      virtually all CD8-positive cells, were stimulated in vitro with pokeweed mitogen
      plus Staphylococcus aureus Cowan I in the presence or absence of various
      neutralizing anti-cytokine antibodies. Numbers of CD5+ and CD5- immunoglobulin
      secreting cells were determined using the protein A haemolytic plaque assay after
      labelling B1a cells with anti-CD5-coated beads. Antibodies against IL-2, IL-5 and
      IL-10 had little or no effect on plaque-forming cell (PFC) induction; anti-IL-6, 
      TNF alpha and -TGF beta enhanced PFC induction; anti-IL-1 alpha, -IL-1 beta, -IL
      4, -IFN gamma and -IL-13 suppressed PFC induction. B1a and B2 cells were equally
      affected by cytokine deprivation using these 11 neutralizing antibodies. In
      contrast, neutralizing anti-IL-12 suppressed induction of CD5+ but not CD5- PFC.
      Furthermore, recombinant IL-12, if added during the first 48 h of culture,
      enhanced CD5+ PFC induction while marginally suppressing (IgG-) or not affecting
      (IgA-, IgM-) induction of CD5- PFC. IL-12 did not preferentially increase
      survival in culture of B1a cells nor induce expression of CD5 on B2-cells.
      Further studies are required to determine whether manipulation of B1a and B2
      subsets in vivo using IL-12 could be achieved in clinical situations where
      imbalances in the two populations have been observed.

PMID- 8560199
TI  - CD5+B cells: differential capping and modulation of IgM and CD5.
AB  - CD5 is associated with the B-cell antigen receptor (BcR) complex. As an approach
      to understanding its role in B-cell function, the authors investigated the
      capping and modulation of CD5 and surface IgM (sIgM). Tonsillar B cells were
      treated with anti-IgM or anti-CD5 antibodies, capping examined after 1 h (by
      fluorescence microscopy) and modulation after 24 h (by flow cytometry). CD5 co
      capped and co-modulated with sIgM. Of various drugs tested, only the protein
      tyrosine kinase inhibitor (genistein) had any effect on capping and co-capping.
      Capping of sIgM (and co-capping of CD5) but not capping of CD5 (or co-capping of
      sIgM) was inhibited by genistein. None of the other drugs affecting PKC or
      cytoskeletal structures (colchicine and cytochalasin D) had any effect. However,
      the PKC inhibitors, staurosporine and H-7, inhibited the modulation of sIgM by
      anti-IgM but not CD5 by anti-CD5. In contrast, PKC activators, PMA and mezerein,
      inhibited modulation of CD5 by anti-CD5 but not sIgM by anti-IgM. This suggests
      that direct ligation of CD5 utilizes different signalling pathways compared with
      sIgM. It seems likely that in CD5+ cells, interaction of CD5 with its ligand CD72
      modulates signals transmitted through the BcR.

PMID- 8560200
TI  - Presynaptic membrane receptor-reactive T lymphocytes in myasthenia gravis.
AB  - The majority of patients with myasthenia gravis were shown to have T and B cells
      specific for a beta-bungarotoxin binding protein, presynaptic membrane receptor
      (PsmR). Such autoreactive T cells may be subdivided into different subsets
      according to the pattern of cytokine production. In this study the authors
      examined the subpopulation of the T cells by analysing their IFN-gamma and/or IL
      4 secretion pattern. T cell response to human muscle acetylcholine receptor
      (AChR) was examined in parallel. PsmR-stimulated IFN-gamma secretion was found in
      60%, and IL-4 secretion in 48% of the patients. Cells stimulated to secrete both
      IFN-gamma and IL-4 or IFN-gamma only were the most common patterns. Treatment of
      the cells with a mouse anti-human HLA-DR antibody abolished the secretion of
      cytokines. There was a positive correlation between the numbers of PsmR-reactive
      and AChR-reactive T cells. In conclusion, the results show that PsmR-stimulated T
      cells secreted IFN-gamma and/or IL-4. This T cell response is MHC class II
      restricted. Thus, this study indicates that both Th1/Th2 or Th0 subsets of the T
      cells are involved in the autoimmune response in the disease.

PMID- 8560201
TI  - Chagasic patients lack CD28 expression on many of their circulating T
      lymphocytes.
AB  - A balanced host-parasite interaction during Trypanosoma cruzi infection allows
      for the establishment of a chronic infection that can last for many years. T
      cells are a major element responsible for parasite specific and non-specific
      immunity during the complex immune response of the host. However, the
      subpopulations of T cells involved in the response, as well as the exact
      mechanisms through which those cells are activated or rendered unresponsive, are
      not well defined. It is known that co-stimulatory signals, some of which are
      mediated via CD28, are of critical importance in the triggering of appropriate T
      cell responses. In this study the authors performed double-labelling studies to
      determine the frequency of expression of CD28 by CD4+ and CD8+ T lymphocytes in
      the peripheral blood of patients with Chagas' disease. The results show that
      chagasic patients throughout the spectrum of chronic clinical forms of the
      infection have significantly higher mean frequencies of CD4+CD28- and CD8+CD28-T
      cells, as compared with non-chagasic individuals. Considering the importance of
      CD28 for T-cell activation, the observed down-regulation or loss of CD28 during
      infection may indicate a possible basis for observed immunoregulatory events or
      distinct stages of T-cell activation in this infection. Recent evidence from
      patients with HIV/AIDS indicates that CD28- cell populations are more likely to
      undergo apoptosis, and increased apoptosis has been observed in experimental
      Chagas disease.

PMID- 8560202
TI  - Histaminergic regulation of natural killer cell-mediated clearance of tumour
      cells in mice.
AB  - Treatment of Swiss albino mice with histamine enhanced the clearance of natural
      killer (NK)-cell sensitive YAC-1 lymphoma and B16/F10 melanoma cells from lung
      tissue in vivo, but did not affect the elimination of NK-cell-insensitive P815
      mastocytoma cells. The effect of histamine was apparently mediated by H2-type
      histamine receptors (H2R) since it was blocked by ranitidine, and H2R antagonist.
      Histamine did not affect clearance of tumour cells in animals depleted of NK
      cells in vivo by treatment with antibodies to asialo-GM1 or NK1.1. The effect of
      histamine was time-dependent: pretreatment with histamine for 3 h significantly
      augmented the clearance of YAC-1 cells, whereas, pretreatment with histamine for
      5 min was ineffective. Histamine potentiated the anti-tumour properties of NK
      cell activators such as interleukin-2 (IL-2) or interferon-alpha (IFN-alpha) in
      vivo. None of these lymphokines significantly affected the clearance of YAC-1
      cells unless animals were concomitantly treated with histamine. Treatment with
      ranitidine alone reduced the in vivo clearance of YAC-1 cells from lungs but did
      not affect the clearance of NK-cell-insensitive P815 cells. Effects of ranitidine
      on NK-cell function in vivo were not shared by a chemical control to ranitidine,
      AH20239AA, thus indicating that the inhibition of NK-cells results from H2R
      antagonism rather than non-specific toxicity. It is concluded that histaminergic
      mechanisms may be involved in the regulation of NK cell function in vivo.

PMID- 8560203
TI  - IFN-gamma restores HIV- and non-HIV-specific cell mediated immune response in
      vitro and its activity is neutralized by antibodies from patients with AIDS.
AB  - The addition of IFN-gamma to cultures of peripheral blood mononuclear cells
      (PBMCs) obtained from asymptomatic HIV-infected patients increased cell
      proliferation in response to HIV envelope synthetic peptides (Env), influenza A
      virus (VIRUS), and allogeneic lymphocytes (ALLO) but not to phytohaemagglutinin
      (PHA) stimulation. F(Ab)2 fragments of IgG purified from the sera of HIV
      seropositive patients specifically interfered with IFN-gamma-induced cell
      proliferation in response to recall antigens. Neutralization of the lymphokine
      activity was found to be sustained by specific IFN-gamma antibodies. Data
      obtained demonstrate that IFN-gamma can restore the cell-mediated immunity of a
      number of asymptomatic HIV+ individuals in vitro, while IFN-gamma antibodies
      present in sera of patients with AIDS interfere with the activity of the
      lymphokine.

PMID- 8560205
TI  - 44th Annual meeting of the Scandinavian Association for Thoracic Surgery.
      Abstracts.

PMID- 8560204
TI  - Changing the ecology of residential units for profoundly and severely mentally
      handicapped adults. A quasi-experimental investigation of generalization and
      maintenance of behavior change.

PMID- 8560206
TI  - The bacteria behind ulcers.

PMID- 8560207
TI  - Keeping vaccines cold. Travails of immunizing the world's children.

PMID- 8560208
TI  - Fluoridation.

PMID- 8560209
TI  - The doctor glut. Experts debate predictions of a physician surplus.

PMID- 8560210
TI  - Schizophrenia revisited. New studies focus on malfunctions in the brain.

PMID- 8560211
TI  - A harebrained scheme. Experimental rabbit-killing virus runs amok in Australia.

PMID- 8560212
TI  - A new way to spell relief: v-e-n-o-m. A toxin from killer sea snails promises a
      better painkiller.

PMID- 8560213
TI  - Profile: Daniel C. Dennett. Dennett's dangerous idea.

PMID- 8560214
TI  - Malnutrition, poverty and intellectual development.

PMID- 8560215
TI  - Telomeres, telomerase and cancer.

PMID- 8560216
TI  - Radiostrontium transfer to sheep's milk as a result of soil ingestion.
AB  - Soil ingestion as a source of radiostrontium contamination of ruminant milk
      products was studied by measuring the transfer coefficient to ovine milk. This is
      a follow-up report from a previous experiment (Assimakopoulos et al., 1993),
      which investigated radiocaesium transfer to sheep's milk as a result of soil
      ingestion. Milk samples from three lactating ewes, housed in individual
      metabolism cages, were used. Fifty grams per day of heavily contaminated sandy
      topsoil, collected in the Chernobyl area, were administered orally to the animals
      for a period of 1 week. The daily intake of 90Sr was 78 Bq day-1. During this
      contamination period, daily milk production and excreta output were measured.
      Excreta and milk was collected for an additional 7-day decontamination period,
      while they were fed on uncontaminated feed. The transfer coefficient was obtained
      through a best fit (minimum chi 2) of the data to predictions of a linear
      compartment model. The value obtained was fm = 0.041 +/- 0.016 d kg-1 for
      radiostrontium transport to milk. This result suggests that soil ingestion can be
      a major source of radiostrontium contamination in sheep and other free-grazing
      ruminants.

PMID- 8560217
TI  - Survey of bioavailable selenium in Sweden with the moose (Alces alces L.) as
      monitoring animal.
AB  - Liver tissues were collected from moose (Alces alces L.) from the regular hunting
      seasons of 1981 and 1982. The material (from about 4300 animals) was stored at 
      20 degrees C at the National Veterinary Institute (SVA). From this material, 2080
      specimens from 12 counties representing 14 regions were analyzed for selenium.
      The counties included were Norrbotten, Vasternorrland (northern region), Uppsala,
      Kopparberg, Gavleborg, Jamtland (central region), north and south Kalmar (eastern
      region), Halland, north and south Alvsborg (western region), and Blekinge,
      Kristianstad and Malmohus (southern region). The analysis was performed by a
      combination of continuous hydride generation using a flow-injection technique and
      atomic absorption spectrometry. The median selenium concentration in the liver in
      the entire material was 0.15 and the mean (+/- S.D.) 0.25 +/- 0.29 (range: 0.03
      3.1) mg/kg wet wt. The highest median values obtained were 0.26, 0.28 and 0.29
      mg/kg, in the counties of Gavleborg (central region) and north and south Alvsborg
      (western region), respectively. The lowest medians, 0.09-0.10 mg/kg, were found
      in the counties of Uppsala (central region), north and south Kalmar (eastern
      region), and Jamtland (central region). Intermediate median values were obtained
      in the other counties: 0.13 mg/kg in the county of Vasternorrland (northern
      region), 0.15-0.16 mg/kg in the counties of Blekinge and Malmohus (southern
      region) and Norrbotten (northern region), 0.18 mg/kg in the county of Halland
      (western region), and 0.23 mg/kg in the counties of Kristianstad and Kopparberg
      (southern and central regions, respectively). Selenium concentrations < 0.1 mg/kg
      in the liver of cattle are considered to be deficient. In some of the regions, 50
      60% of the moose livers showed values below this level. The results indicate that
      the moose is useful for monitoring the amount of selenium available for wild
      grazing animals and confirm that the Swedish environment is poor in selenium.

PMID- 8560218
TI  - Function of the rat salivary glands after exposure to inorganic mercury.
AB  - In spite of many studies on the toxicity of mercury, very little is known about
      the effects of mercury on the function of exocrine glands. In the present paper
      selected functions of Sprague-Dawley rat salivary glands were studied after the
      exposure of the animals to inorganic mercury at two different doses; 3.25 mg/kg
      body weight given during 25 days and 7.0 mg/kg body weight given during 27 days.
      The function of the salivary glands was estimated by saliva secretion rate,
      secretion of electrolytes, proteins and biosynthesis of glycoproteins. The
      function was compared between mercury exposed rats and age and sex matched
      control rats that were given injections with equal volumes of 0.154 mol/l NaCl on
      the same time schedule. In the present study we report that no significant effect
      on saliva secretion rate, concentrations of salivary constituents or biosynthesis
      of glycoproteins in the salivary glands could be observed in rats as a result of
      mercury exposure at two levels that gave 30 or 60 times higher serum mercury
      concentrations than in the majority of the Swedish population.

PMID- 8560219
TI  - Technetium-99, iodine-129 and tritium in the waters of the Savannah River Site.
AB  - Surface water samples were collected from streams on and around the Savannah
      River Site (SRS) to assess current 3H, 99Tc, and 129I concentrations in the
      water. The SRS is a nuclear facility operated by Westinghouse Savannah River
      Company for the US Department of Energy. Water quality parameters were measured
      at the time of collection using field portable instrumentation. The tritium
      activity was determined by liquid scintillation spectrometry. The isotopes, 99Tc
      and 129I, were determined by isotope dilution/inductively coupled plasma-mass
      spectrometry (D.M. Beals, Determination of technetium-99 in aqueous samples by
      isotope dilution inductively coupled plasma-mass spectrometry. Presented at the
      3rd International Conference on Nuclear and Radiochemistry, Vienna, September
      1992, unpublished data; D.M. Beals, P. Chastagner and P.K. Turner, Analysis of
      iodine-129 in aqueous samples by inductively coupled plasma-mass spectrometry.
      Presented at the 38th Annual Conference on Bioassay, Analytical and Environmental
      Radiochemistry, Santa Fe, NM, November 1992). Elevated activities of 3H, 99Tc,
      and 129I were found in some surface streams of the SRS, principally due to
      migration of ground water from beneath old seepage basins, however the levels in
      the waters leaving the SRS are well below any regulatory guidelines.

PMID- 8560220
TI  - Low-level analysis of lead-210 in waters via bismuth-210 measurement.
AB  - This communication reports the development of an analytical method for the
      measurement of low-levels of lead-210 in natural waters via measurement of the
      beta activity of its in-grown bismuth-210 daughter. The analysis essentially
      consists of three stages. (a) Pre-concentration of the lead-210 in a known volume
      of water by co-precipitation with a mixed barium/lead sulphate, where the
      efficiency of the step is determined by gamma measurement of a barium-133
      internal tracer. (b) Separation of the in-grown bismuth-210 from its lead-210
      parent by solvent extraction of a bismuth carrier into a solution of
      diethylammonium diethyldithiocarbamate (DDTC) in chloroform. (c) Preparation of a
      bismuth oxychloride source for gross beta counting to determine the bismuth-210
      activity. The reported method is capable of achieving a detection limit (4 sigma
      b) of < 10 mBq/l.

PMID- 8560221
TI  - Investigations of the potential bioavailability of 210Po in some foodstuffs.
AB  - Extraction of 210Po from lamb's liver, pig's kidneys, mussel flesh and brown
      crabmeat with a series of solvent systems has been used to gain some insight into
      the uncertainty about the gastrointestinal absorption factor for Po incorporated
      into foodstuffs. By extracting the tissues with diethyldithiocarbamate dissolved
      in chloroform, and also in methanol, it has been shown that 210Po is more
      effectively extracted from lamb's liver and crabmeat than it is from each of the
      other tissues. A similar pattern of extractability is also evident for aqueous
      solutions of citric acid on crabmeat and mussel flesh. Of particular note is the
      low extractability by dimethylsulphoxide (3%) of 210Po in mussel flesh as opposed
      to 24% extractability of 210Po from crabmeat. 210Po-binding macromolecules of
      about 10 kDa have been released from crabmeat and mussel flesh by digestion with
      pepsin.

PMID- 8560222
TI  - The determination of low levels of radiocaesium and radioruthenium in foodstuffs.
AB  - The Ministry of Agriculture, Fisheries and Food (MAFF) has the responsibility for
      safeguarding the food supply from authorised and accidental releases of
      radioactivity to the environment. MAFF funds a radiological research programme to
      assist in the achievement of its objectives and has recognised that there is a
      continuing requirement to develop cost effective and sensitive analytical methods
      for the detection of very low levels of radioactivity in foodstuffs. High
      resolution gamma spectrometry is often the most appropriate analytical method for
      the determination of 103Ru, 106Ru, 134Cs and 137Cs but the detection limits for
      these radionuclides in bulk foodstuffs do not permit the acquisition of accurate
      data at very low levels. Beta counting techniques offer inherently higher
      sensitivities but the development of radiochemical separation techniques is
      essential to provide appropriate counting sources. A radiochemical separation
      method has been developed for the determination of radiocaesium and
      radioruthenium in 0.5 kg fresh wt samples of a variety of foodstuffs. The method
      was shown to be robust and specific and mean method recoveries of 75% were
      obtained for both radiocaesium and radioruthenium. MDA's for the 1000 min counts
      on a gas-flow proportional counter were determined to be 0.015 Bq/kg fresh wt for
      both 137Cs and 106Ru.

PMID- 8560224
TI  - Pilot study of labelling bovine muscle tissue with 14C.
AB  - A pilot study has been performed to assess the feasibility of labelling bovine
      muscle tissue with 14C, in order to produce material suitable for intercomparison
      exercises. Approximately 1 kg of tissue was prepared by grinding, blending,
      labelling with 14C-methylated bovine haemoglobin and thoroughly mixing by
      repeated blending. The product was sealed in cans and sterilized to preserve it.
      Portions of raw material were dried to test the homogeneity of moisture content.
      Homogeneity of 14C in the natural and labelled materials was tested by analyzing
      sub-samples of 2-3 g in weight of the freeze-dried materials. The 14C content was
      determined by combusting and collecting the CO2 for liquid scintillation
      counting. The material was found to be homogeneous to the extent of 2-4%
      (R.S.D.), which is comparable with the R.S.D. of the 14C measurements. The 14C
      concentration in the labelled material was 8190 +/- 220 Bq.kg-1 of carbon. It was
      concluded that bovine muscle prepared in this manner would be suitable for
      intercomparison exercises. The 14C level in unlabelled tissue was found to be 260
      +/- 7 Bq.kg-1 of carbon, which is similar to the level of 14C previously
      determined in milk and both are consistent with levels measured in vegetation in
      Eastern Ontario.

PMID- 8560223
TI  - Determination of strontium-90 in milk samples using a controlled precipitation
      clean-up step prior to ion-chromatography.
AB  - Strontium-90 may be determined by beta-counting its yttrium-90 daughter following
      separation by ion-chromatography, using a three column system comprising a
      chelating concentrator column, a cation-exchange column and an anion-exchange
      separator column. The column system has previously been applied to the
      determination of strontium-90 in water and urine samples. The applicability of
      the system to the analysis of milk is hampered by the large concentrations of
      calcium present, which significantly reduces the extraction of yttrium-90 by the
      concentrator column. A maximum of approximately 200 mg of calcium can be present
      for the successful extraction of yttrium-90, which greatly limits the quantity of
      milk that can be analysed. The quantity of milk analysed can be increased by the
      inclusion of a controlled precipitation step prior to the ion-chromatographic
      separation. The precipitation is carried out on acid digested milk samples by the
      addition of ammonia solution until the addition of one drop causes a reduction in
      pH resulting in the precipitation of calcium hydrogenphosphate. Under these
      conditions, approximately 20% of the calcium present in the original milk sample
      is precipitated, yttrium-90 is precipitated whereas strontium-90 is not
      precipitated. Dissolution of the precipitate, followed by separation of yttrium
      90 using the ion-chromatography system facilitates the analysis of a litre of
      milk with recoveries of greater than 80%.

PMID- 8560225
TI  - Distribution of toxic and radiation components in air particulates.
AB  - The concentrations of several toxic heavy metals and volatile organic compounds
      (VOCs) in various types of Hungarian fly-ash fine particulates were investigated
      by means of instrumental neutron activation analysis, X-ray fluorescence analysis
      and gas chromatography, coupled with mass spectrometry. Within a power station,
      particulate samples were taken from the boiler zone (BO), from the electrostatic
      dust filter chamber (FI) and from the flue-gas at the top of the stack (ST).
      Enrichment rates of the toxic metals both in FI and ST particulate fractions
      related to the BO concentrations were calculated to enable the temperature
      dependence on the adsorption of the toxic components to be studied. In addition,
      both the total amounts of the VOCs and their partial distributions in accordance
      with the number of carbon atoms were also studied in fly-ash particulates. From
      them, 31 organic species were identified and determined. Since Hungarian brown
      coals have high uranium and thorium contents, the specific radioactivities of the
      daughter isotopes of both the 232Th and 238U decay series were also measured and
      are discussed.

PMID- 8560226
TI  - The impact of heavy metals from environmental tobacco smoke on indoor air quality
      as determined by Compton suppression neutron activation analysis.
AB  - The method of instrumental neutron activation analysis (NAA) has been improved
      for air filter samples in the determination of low level heavy metals in indoor
      air. By using the techniques of epithermal neutron irradiation in conjunction
      with Compton suppression, the detection limits of cadmium, arsenic and antimony
      measurements have been dramatically reduced to 2 ng for Cd, 0.2 ng for As, and
      0.03 ng for Sb. The determination of these heavy metals in particulate material
      generated from cigarette smoking in indoor environments has been conducted. Other
      elements, Br, Cl, Na, K, Zn were also found at elevated levels.

PMID- 8560227
TI  - The determination of 129I in milk and vegetation using neutron activation
      analysis.
AB  - A new method has been developed to measure 129I in the environment with detection
      limits below 10 mBq/kg of vegetation and 10 mBq/l of cows' milk. The method is
      based on extraction of 129I from the milk or vegetation sample, onto an ion
      exchange resin. An inactive carrier of 127I is added to the sample before
      separation, to monitor losses throughout the entire procedure. The ion exchange
      resin is irradiated for 7.5 h in a neutron flux of 10(16) n m-2 s-1 to induce the
      129I(n, gamma) 130I reaction with thermal neutrons. The 127I carrier undergoes a
      (n,2n) reaction with fast neutrons to produce 126I. Iodine is extracted from the
      ion exchange resin after irradiation with an elution scheme which removes
      contamination from the radionuclide 82Br, the main interference in the analysis.
      Finally iodine is precipitated as AgI for gamma ray analysis. The sample is
      counted for 3 h on a Ge semiconductor detector to measure the radionuclide 130I,
      which has a half life of 12.4 h and 126I, which has a half life of 13.0 days. The
      measured 130I activity is compared to a known standard to deduce the amount of
      129I in the sample, and the concentrations are corrected for losses during
      processing using the measured activity of 126I. The detection limits for 129I by
      this method are below 10 mBq/l for milk samples and 10 mBq/kg for vegetation. In
      addition to routine monitoring of milk and grass samples the method has been used
      to measure 129I deposition on grass and soils in a field near the Sellafield
      plant. Results of these analyses, along with measurements of 129I in air and
      rainfall using the same methodology, have been used to determine deposition
      velocity and retention coefficients of 129I to grass.

PMID- 8560228
TI  - Transfer of radionuclides to vegetable and other crops grown on land reclaimed
      from the sea.
AB  - An area of reclaimed land on the Lancashire coast has been used to grow a wide
      range of crops to provide data on transfer parameters of radionuclides in
      foodchains when the activity is almost entirely of marine origin. Activity
      concentrations in the foodstuffs were low and not of radiological significance.
      However, meaningful results could be obtained if large sample sizes were
      employed. This paper sets out the methodology applied to a substantial field
      investigation of transfer to vegetable crops. The large sample sizes could be
      accommodated adequately with only minor modifications to established analytical
      procedures. The results of the study are discussed briefly. Since the growing
      conditions were virtually identical for each crop, comparisons of transfer
      factors between the different crops should therefore be valid. For some
      radionuclides, notably 239,240Pu, 241Am and 99Tc, the work has added
      significantly to the data that are presently available. For most of the
      radionuclides studied, uptake by crops could be adequately predicted using the
      parameter values currently used in generic assessments, but for 99Tc, lower
      values would be more appropriate.

PMID- 8560229
TI  - The effect of dialysis on radiocaesium in man.
AB  - Dialysis is used for cleaning the blood in patients with end-stage renal disease.
      The most common methods are hemodialysis (HD) and peritoneal dialysis (PD).
      Dialysis patients might constitute a critical group because of poor elimination
      of radioactive elements ingested. On the other hand dialysis may be a useful
      decontamination method for radioactivity. The effect of dialysis on the turnover
      of radiocaesium was studied in 10 HD patients and 4 PD patients. The dialysis
      fluid, which contains electrolytes and the metabolic waste products, was analyzed
      for radiocaesium. In this connection the patients were whole-body counted for
      radiocaesium and 40K. The results show that HD patients generally have a lower
      body burden of radiocaesium than normal subjects, while PD patients show normal
      levels. At steady state both dialysis methods eliminate slightly less
      radiocaesium than normal kidneys do, but in the case of HD during a much shorter
      time. The calculated effective half-life for radiocaesium was normal in the HD
      patients, and somewhat longer in the PD patients. Considering that HD is
      performed only for 12-15 h weekly, the elimination rate of radiocaesium by HD is
      much higher compared with that by normal kidneys. Thus, HD might constitute an
      important method for decontamination of radiocaesium after accidental internal
      contamination.

PMID- 8560230
TI  - A field study of tritium migration in groundwater.
AB  - A field study of tritium migration from an underground nuclear explosion was
      carried out for more than 7 years. A series of satellite wells was drilled around
      the explosion cavity, which is within a nuclear test site water-supply aquifer.
      Samples from various wells were analysed. In this way, variations in the tritium
      concentration of water from different wells were determined, and the extent of
      tritium migration during the 7 years after the detonation was examined. The
      maximum tritium concentration reached in water from various wells is just 52
      times higher than the maximum permissible concentration for drinking water and
      decreased afterwards. According to the results obtained, the flow rate of
      groundwater was inferred to be about 91 m per year and the maximum contamination
      distance of water supplies by the tritium were < or = 2 km from the explosion
      cavity.

PMID- 8560231
TI  - Application of Cerenkov radiation for the assay of 226Ra in natural water.
AB  - A Cerenkov based method has been developed for the determination of 226Ra via its
      beta-emitting daughters, 214Bi and 214Pb. Radium isotopes are separated from
      interfering elements by coprecipitation on barium sulphate. The precipitate is
      dissolved in an alkaline solution of EDTA and the Cerenkov signal produced by the
      build-up of daughter beta activities is counted after 25 days using the tritium
      channel of a liquid scintillation counter. To correct for any contribution from
      the daughters of the radium isotopes 224Ra and 228Ra present in the sample, the
      barium(radium) sulphate is reprecipitated, dissolved in EDTA, and counted 2 days
      later. Using this procedure, 228Ra can be determined in the same sample. Cerenkov
      counting efficiency was found to be 77.25%. A lower limit of detection of 17.4
      mBq l-1 (based on 3 sigma of the background with 500 min counting time) was
      achieved. Any liquid scintillation counter can be used. Chemical recoveries in
      the range 75-95% were determined gravimetrically. Data from both artificial
      spiked samples and natural samples are presented.

PMID- 8560232
TI  - Optimization and comparison of three different methods for the determination of
      Rn-222 in water.
AB  - Three different systems for the determination of radon in water have been
      examined: liquid scintillation counting (LSC), degassification followed by Lucas
      cell counting (LCC) and gamma counting (GC). Particular care has been devoted to
      the sampling methodologies of the water. Comparative results for several
      environmental samples are given. A critical evaluation is also given on the basis
      of the final aim of the measurements.

PMID- 8560233
TI  - Characterisation of Nile and drinking water quality by chemical and cluster
      analysis.
AB  - Nile- and drinking water samples were collected from several locations between
      Aswan city and Cairo before and during the flood. Short-time activation analysis
      was applied to determine the concentrations of Al, Ca, Cl, F, K, Mg, Na and V,
      while Ba, Cr, Co, Fe, Hf, Rb, Sb, Sc and Zn were determined by irradiating the
      samples for 20 h at a neutron flux of 1.8 x 10(12) cm-2 s-1. The values of
      dissolved oxygen, nitrate, sulphate, orthophosphate, organic matter and the pH
      were determined by applying the standard methods. All data were examined
      statistically, and classified using cluster analysis technique. The results show
      that the concentrations of the major and trace elements in drinking water are
      higher compared with their levels in Nile water. This indicates that the water
      pumped from the Nile for use as drinking water is mixed with underground water
      before supplying. It has also been found that the concentrations of nitrate and
      phosphate in Nile water are significantly higher in Aswan than in those taken
      from the lower parts of the Nile. Cluster analysis proved to be an ideal
      technique for classifying these types of samples according to their sampling time
      and sites.

PMID- 8560234
TI  - Residual Chernobyl fallout and Sellafield pollutants found on the Isle of Man.
AB  - The Isle of Man is particularly vulnerable to radioactive pollution being located
      in the middle of the Irish Sea, only 55 km from the Sellafield nuclear site.
      Paradoxically, radioactive fallout from the accident at Chernobyl is the only
      significant radioactive pollution on the Island and requires legal restrictions
      on sheep farming. This paper gives an overview of the occurrence and magnitude of
      radioactive pollution on the Isle of Man, using results of live-monitoring of the
      Island's hill flocks since August 1987, and data selected from the results of
      laboratory analysis of more than 1000 samples of foodstuffs and environmental
      materials between 1990 and 1993. Radioactive contamination is of no significance
      in local agricultural produce, however, about one sixth of the Island's hill
      grazing land is still subject to controls. Sellafield pollutants are found only
      in samples from the marine environment.

PMID- 8560235
TI  - A rapid method for the detection of uranium in surface water.
AB  - A method has been optimized to preconcentrate uranium from waters using the ion
      exchanger Hyphan. The sample (up to 10 1) is agitated thoroughly with a portion
      of the ion exchanger for between 40 min and 2 h. The exchanger is filtered off
      and treated with a small volume (< 100 ml) of either nitric acid (for ICP
      measurement) or hydrochloric acid (for alpha measurement). The acid is filtered
      off and measured directly by ICP-AES, or it is brought to pH 2 and saturated with
      ammonium chloride, then directly electrolyzed. Yields lie in the order of 60-90%
      and the overall analysis time is approximately 3 h (ICP) or approximately 4 h
      (alpha measurement). Precisions reached are better than 15% relative. Detection
      limits lie at about 2 ppb (ICP) and 0.4 ppb (alpha measurement).

PMID- 8560236
TI  - Determination of natural radionuclides in drinking water; a tentative protocol.
AB  - Routine analysis of drinking water is in general limited to artificial
      radionuclides although some naturally occurring radionuclides have
      radiotoxicities well comparable to those of the worst artificial ones. This
      unsatisfactory situation is mainly due to problems with traditional radiochemical
      preparation methods. They are very time consuming and the chemistry involved is
      too high a hurdle for many laboratories. A simplified protocol for the
      determination of natural radionuclides in drinking water has been setup and
      tested. It makes full use of the gamma-spectrometry's analyzing power and of
      state-of-the-art liquid scintillation alpha-spectrometry combined with extractive
      scintillators. It also includes the use of metal-adsorbing thin layers for direct
      alpha-spectrometry. The protocol does not offer record-low detection limits, but
      allows for a rapid check that no individual natural radionuclide present in the
      water will contribute more than 50 microS v to the annual dose.

PMID- 8560237
TI  - Trace element concentrations in cetacean liver tissues archived in the National
      Marine Mammal Tissue Bank.
AB  - The National Biomonitoring Specimen Bank (NBSB), a collaborative project of
      several U.S. government agencies, includes marine mammal tissues collected for
      the Alaska Marine Mammal Tissue Archival Project (AMMTAP) and the National Marine
      Mammal Tissue Bank (NMMTB). Tissues were collected from 139 animals representing
      13 species of marine mammals from around the U.S. Recently, concentrations for up
      to 30 elements in liver tissues of nine long-finned pilot whales (Globicephala
      melas), six harbor porpoises (Phocoena phocoena), and four white-sided dolphins
      (Lagenorhynchus acutus) from the NMMTB were measured using instrumental neutron
      activation analysis. Results from analyses of these tissues are presented,
      compared with results for liver tissues from other marine mammals from the
      AMMTAP, and compared with published values.

PMID- 8560238
TI  - Concentrations of Cu, Cd, Ni, and Pb in the blood and tissues of cancerous
      persons in a Pakistani population.
AB  - The Cu, Cd, Ni, and Pb contents of blood and tissue samples of some cancer
      patients in a Pakistani population were measured by atomic absorption
      spectroscopy. The results were compared with those found in the blood samples of
      healthy controls selected from persons with known previous health record. The
      trace element contents were found to be different in various cancer types, age
      groups, and between male and females. The results of this investigation showed
      that the average Cd and Ni concentrations were higher in the blood of cancer
      patients as compared to controls. Copper levels in the blood of male cancer
      patients were higher than the controls and the opposite was the case for females.
      The concentration levels of Pb in the blood were almost the same in all groups.
      In cancerous tissues the concentrations of Cu were found to be lower as compared
      to the unaffected part of the same organ of the same patient. The relationship of
      Cd and Ni to carcinogenesis is well established now and their abnormal levels
      could indicate an exposure to them. Changes in copper levels could be due to the
      altered metabolic requirements of the subjects under biological stress i.e.
      presence of cancer.

PMID- 8560239
TI  - The femur capitulum as a biomarker of contamination due to indicating lead
      content in the air by participation of the other metals.
AB  - The occurrence of nine elements in the coxarthrosis human femoral capitula is
      described. The atomic absorption spectrophotometry (AAS) method was used to
      determine Cd, Pb, Cr, Cu, Mn, Fe, Zn, Ni and Co concentrations in the three kinds
      of tissues: spongious and cortical bone and joint surface cartilage. Based on the
      Pb bone concentrations, an ecotoxicological Pb contamination risk for the
      industrial region can be predicted.

PMID- 8560240
TI  - Accidental contamination from uranium compounds through contact with ceramic
      dinnerware.
AB  - Examination of orange-colored dinnerware samples purchased in antique stores and
      flea markets has revealed the occasional presence of surface uranium compounds
      that are readily transferred to the hands and clothing. We have further been able
      to produce soluble uranium compounds on the surfaces of clean dishes by exposing
      them to household vinegar or bleach. We estimate that handling of a contaminated
      dish can transfer up to 1-2 becquerels or more of uranium compounds to the hands.
      Uranium contamination is of concern because the element is not only an alpha
      emitter but also a chemical nephrotoxin. Although the amount of uranium likely to
      be ingested as a result of casual handling may be small, it could still exceed by
      several times the amount occurring in the average diet (about 40 mBq/day).
      Furthermore, since fresh surface compounds are readily formed, it is possible
      that a person who regularly handles or eats from uranium-glazed dinnerware can
      accidentally ingest significant amounts of uranium.

PMID- 8560241
TI  - Human hair mercury levels in Tucurui area, State of Para, Brazil.
AB  - The environmental mercury contamination at the Tucurui water reservoir was
      studied by measuring the amount of mercury in human hair samples collected from
      fishermen and their families. Samples were also collected from the Parakana
      Indian reservation in the vicinity to give information about the background
      levels in the area. The mercury concentrations in hair samples ranged from 0.9 to
      240 mg/kg. The mean value in the main reservoir was 65 mg/kg. Seven values
      exceeded 100 mg/kg and 31 values exceeded 50 mg/kg. The hair Hg concentrations
      amongst the fishermen in Tucurui reservoir are high enough to cause health
      effects. The fetal exposure is especially alarming. Changes in gold mining
      practises and in the human diet are recommended.

PMID- 8560242
TI  - Mercury and methylmercury in fish and human hair from the Tapajos river basin,
      Brazil.
AB  - Mercury is being released in the Amazon in an abusive way due to goldmining
      activities. The Tapajos river basin was the first to be intensively exploited in
      the modern Amazon gold rush. Fish and hair samples as the best indicators of
      human methylmercury contamination were investigated in the main cities and
      villages along the Tapajos river basin. The upper basin has typical fish fauna
      with much larger carnivorous fish with higher mercury levels reaching an average
      value of 0.69 microgram.g-1 wet wt. in 43 fish. This was accompanied by high
      levels in hair of the human population living in the same area. The maximum hair
      value reach 151 micrograms.g-1 dry wt. with two villages presenting an average
      value close to 25 micrograms.g-1 dry wt. An analytical laboratory
      intercalibration exercise was performed between Japanese and Brazilian
      laboratories for total mercury analysis. Critical fish, areas, and more exposed
      human groups are identified.

PMID- 8560243
TI  - On heavy metals in soil; rationalization of extractions by dilute salt solutions,
      comparison of the extracted concentrations with uptake by ryegrass and lettuce,
      and the possible influence of pyrophosphate on plant uptake.
AB  - Extractions of Cu, Zn, Cd and Pb from soils by dilute salt solutions have been
      rationalized by a simple chemical equilibrium relation which includes the total
      load of metals, soil pH, soil cation exchange capacity (CEC), and extractant
      ionic strength. Correlations between metal uptakes by ryegrass and lettuce with
      calculated concentrations of Cu, Zn, or Cd in a fictitious soil solution at zero
      ionic strength are comparable to those obtained with the weakest salt solutions,
      0.1 mol.l-1 NaNO3 and 0.05 mol.l-1 CaCl2. The other salt solutions correlate
      slightly less well. Uptake of Pb is not represented well.

PMID- 8560245
TI  - NASA's life science.

PMID- 8560244
TI  - Soil and waste analysis for environmental risk assessment in France.
AB  - In France today, analysis of soil and waste after digestion by strong acids is a
      technique used for the estimation of environmental risks due to soil pollution
      and spreading of wastes on cultivated soils. The technique of digestion by strong
      acid accounts for total or 'near total' content of As, Cd, Cr, Cu, Hg, Ni, Pb, Se
      and Zn. Risk management based on these methods aims to minimize the risks, since
      the concentration limits are derived from the geochemical levels. However, this
      method of analysis gives no idea of the extent to which elements are really
      transferable or bioavailable. Analytical methods based on partial extraction are
      used to discern deficiencies in B, Cu, Fe, Mn and Zn in soil. These extractions
      are carried out using boiling water and EDTA or DTPA solutions. The extraction
      methods have been standardized for use in agriculture, but have not been tested
      for assessing the risks due to the pollution by trace elements. One partial
      extraction method has been standardized for the analysis of wastes. It uses
      successive water extractions. Researchers have studied different partial
      extraction methods for estimating the bioavailability of mineral pollutants. Some
      of them gave results which correlated well with the amounts taken up by plants.
      However, at present, no general frame of reference has yet been established for
      the interpretation of results on a broad scale.

PMID- 8560247
TI  - Antisense research.

PMID- 8560246
TI  - NASA's life science.

PMID- 8560248
TI  - State key labs in China.

PMID- 8560249
TI  - AIDS task force fizzles out.

PMID- 8560250
TI  - Policy on DNA research troubles tissue bankers.

PMID- 8560251
TI  - 'Natural' cancer prevention trial halted.

PMID- 8560252
TI  - Can some infants beat HIV?

PMID- 8560253
TI  - Mutant enzyme provides new insights into the cause of ALS.

PMID- 8560254
TI  - Modified microbe may boost TB vaccine.

PMID- 8560255
TI  - Proteins 'clock' the origins of all creatures--great and small.

PMID- 8560257
TI  - Gating by cyclic AMP: expanded role for an old signaling pathway.

PMID- 8560256
TI  - A docking receptor for HDL cholesterol esters.

PMID- 8560258
TI  - BMP-1: resurrection as procollagen C-proteinase.

PMID- 8560259
TI  - Determining divergence times of the major kingdoms of living organisms with a
      protein clock.
AB  - Amino acid sequence data from 57 different enzymes were used to determine the
      divergence times of the major biological groupings. Deuterostomes and protostomes
      split about 670 million years ago and plants, animals, and fungi last shared a
      common ancestor about a billion years ago. With regard to these protein
      sequences, plants are slightly more similar to animals than are the fungi. In
      contrast, phylogenetic analysis of the same sequences indicates that fungi and
      animals shared a common ancestor more recently than either did with plants, the
      greater difference resulting from the fungal lineage changing faster than the
      animal and plant lines over the last 965 million years. The major protist
      lineages have been changing at a somewhat faster rate than other eukaryotes and
      split off about 1230 million years ago. If the rate of change has been
      approximately constant, then prokaryotes and eukaryotes last shared a common
      ancestor about 2 billion years ago, archaebacterial sequences being measurably
      more similar to eukaryotic ones than are eubacterial ones.

PMID- 8560260
TI  - Thiyl radicals in ribonucleotide reductases.
AB  - The ribonucleoside triphosphate reductase (RTPR) from Lactobacillus leichmannii
      catalyzes adenosylcobalamin (AdoCbl)-dependent nucleotide reduction, as well as
      exchange of the 5' hydrogens of AdoCbl with solvent. A protein-based thiyl
      radical is proposed as an intermediate in both of these processes. In the
      presence of RTPR containing specifically deuterated cysteine residues, the
      electron paramagnetic resonance (EPR) spectrum of an intermediate in the exchange
      reaction and the reduction reaction, trapped by rapid freeze quench techniques,
      exhibits narrowed hyperfine features relative to the corresponding unlabeled
      RTPR. The spectrum was interpreted to represent a thiyl radical coupled to
      cob(II)alamin. Another proposed intermediate, 5'-deoxyadenosine, was detected by
      rapid acid quench techniques. Similarities in mechanism between RTPR and the
      Escherichia coli ribonucleotide reductase suggest that both enzymes require a
      thiyl radical for catalysis.

PMID- 8560261
TI  - Reversible encapsulation of disc-shaped guests by a synthetic, self-assembled
      host.
AB  - Here, the synthesis of a bowl-shaped molecule is described and evidence of its
      reversible dimerization by means of hydrogen bonds is presented. The dimer
      features a flattened spherical cavity of peculiar symmetry and acts as a host for
      the encapsulation of guest molecules of complementary shape. Encapsulation of
      aromatic guests in chloroform solution and of cyclohexane in p-xylene solution
      was demonstrated by nuclear magnetic resonance experiments. The passage of guests
      into and out of the cavity is slow and occurs on a time scale of hours. The
      system was used to explore the effects of size, shape, and solvation on molecular
      recognition coupled with assembly.

PMID- 8560262
TI  - Reduction of HIV concentration during acute infection: independence from a
      specific immune response.
AB  - After infection with the human immunodeficiency virus (HIV), the concentration of
      the virus in the person's plasma increases. The subsequent decrease in
      concentration a few weeks later was though to result from an HIV-specific immune
      response. This purported causal relation is investigated with a model of the
      dynamics of early HIV infection that incorporates no increase in the rate of
      removal of free virions or virus-infected cells. A pattern of changes in virus
      concentration similar to that observed in patients is predicted by the model.
      Thus, the reduction in virus concentration during acute infection may not reflect
      the ability of the HIV-specific immune response to control virus replication.

PMID- 8560263
TI  - Dependence of cyclin E-CDK2 kinase activity on cell anchorage.
AB  - Most nonmalignant cells are anchorage-dependent; they require substrate
      attachment for growth and, in some instances, survival. This requirement is lost
      on oncogenic transformation. The cyclin E-CDK2 complex, which is required for the
      G1-S transition of the cell cycle, was activated in late G1 phase in attached
      human fibroblasts, but not in fibroblasts maintained in suspension. In
      transformed fibroblasts the complex was active regardless of attachment. The lack
      of cyclin E-CDK2 activity in suspended cells appeared to result from increased
      expression of CDK2 inhibitors and a concomitant decrease in phosphorylation of
      CDK2 on threonine-160. Suppression of cyclin E-CDK2 activity may thus underlie
      the anchorage dependence of cell growth.

PMID- 8560264
TI  - Angiotensin II-forming activity in a reconstructed ancestral chymase.
AB  - The current model of serine protease diversity theorizes that the earliest
      protease molecules were simple digestive enzymes that gained complex regulatory
      functions and restricted substrate specificities through evolution. Among the
      chymase group of serine proteases are enzymes that convert angiotensin I to
      angiotensin II, as well as others that simply degrade angiotensins. An ancestral
      chymase reconstructed with the use of phylogenetic inference, total gene
      synthesis, and protein expression had efficient and specific angiotensin II
      forming activity (turnover number, about 700 per second). Thus, angiotensin II
      forming activity is the more primitive state for chymases, and the loss of such
      activity occurred later in the evolution of some of these serine proteases.

PMID- 8560265
TI  - Molecular cloning and disease association of hepatitis G virus: a transfusion
      transmissible agent.
AB  - An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma
      of a patient with chronic hepatitis. Extension from an immunoreactive
      complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a
      polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV
      C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was
      associated with acute and chronic hepatitis. Persistent viremia was detected for
      up to 9 years in patients with hepatitis. The virus is transfusion-transmissible.
      It has a global distribution and is present within the volunteer blood donor
      population in the United States.

PMID- 8560266
TI  - Receptor-ligand interaction between CD44 and osteopontin (Eta-1).
AB  - The CD44 family of surface receptors regulates adhesion, movement, and activation
      of normal and neoplastic cells. The cytokine osteopontin (Eta-1), which regulates
      similar cellular functions, was found to be a protein ligand of CD44. Osteopontin
      induces cellular chemotaxis but not homotypic aggregation, whereas the inverse is
      true for the interaction between CD44 and a carbohydrate ligand, hyaluronate. The
      different responses of cells after CD44 ligation by either osteopontin or
      hyaluronate may account for the independent effects of CD44 on cell migration and
      growth. This mechanism may also be exploited by tumor cells to promote metastasis
      formation.

PMID- 8560267
TI  - Activation by attention of the human reticular formation and thalamic
      intralaminar nuclei.
AB  - It has been known for over 45 years that electrical stimulation of the midbrain
      reticular formation and of the thalamic intralaminar nuclei of the brain alerts
      animals. However, lesions of these sectors fail to impair arousal and vigilance
      in some cases, making the role of the ascending activating reticular system
      controversial. Here, a positron emission tomographic study showed activation of
      the midbrain reticular formation and of thalamic intralaminar nuclei when human
      participants went from a relaxed awake state to an attention-demanding reaction
      time task. These results confirm the role of these areas of the brain and
      brainstem in arousal and vigilance.

PMID- 8560268
TI  - Altered reactivity of superoxide dismutase in familial amyotrophic lateral
      sclerosis.
AB  - A subset of individuals with familial amyotrophic lateral sclerosis (FALS)
      possesses dominantly inherited mutations in the gene that encodes copper-zinc
      superoxide dismutase (CuZnSOD). A4V and G93A, two of the mutant enzymes
      associated with FALS, were shown to catalyze the oxidation of a model substrate
      (spin trap 5,5'-dimethyl-1-pyrroline N-oxide) by hydrogen peroxide at a higher
      rate than that seen with the wild-type enzyme. Catalysis of this reaction by A4V
      and G93A was more sensitive to inhibition by the copper chelators
      diethyldithiocarbamate and penicillamine than was catalysis by wild-type CuZnSOD.
      The same two chelators reversed the apoptosis-inducing effect of mutant enzymes
      expressed in a neural cell line. These results suggest that oxidative reactions
      catalyzed by mutant CuZnSOD enzymes initiate the neuropathologic changes in FALS.

PMID- 8560269
TI  - Identification of scavenger receptor SR-BI as a high density lipoprotein
      receptor.
AB  - High density lipoprotein (HDL) and low density lipoprotein (LDL) are cholesterol
      transport particles whose plasma concentrations are directly (LDL) and inversely
      (HDL) correlated with risk for atherosclerosis. LDL catabolism involves cellular
      uptake and degradation of the entire particle by a well-characterized receptor.
      HDL, in contrast, selectively delivers its cholesterol, but not protein, to cells
      by unknown receptors. Here it is shown that the class B scavenger receptor SR-BI
      is an HDL receptor. SR-BI binds HDL with high affinity, is expressed primarily in
      liver and nonplacental steroidogenic tissues, and mediates selective cholesterol
      uptake by a mechanism distinct from the classic LDL receptor pathway.

PMID- 8560270
TI  - Interfering with apoptosis: Ca(2+)-binding protein ALG-2 and Alzheimer's disease
      gene ALG-3.
AB  - Two apoptosis-linked genes, named ALG-2 and ALG-3, were identified by means of a
      functional selection strategy. ALG-2 codes for a Ca(2+)-binding protein required
      for T cell receptor-, Fas-, and glucocorticoid-induced cell death. ALG-3, a
      partial complementary DNA that is homologous to the familial Alzheimer's disease
      gene STM2, rescues a T cell hybridoma from T cell receptor- and Fas-induced
      apoptosis. These findings suggest that ALG-2 may mediate Ca(2+)-regulated signals
      along the death pathway and that cell death may play a role in Alzheimer's
      disease.

PMID- 8560271
TI  - Newly learned auditory responses mediated by NMDA receptors in the owl inferior
      colliculus.
AB  - Alignment of auditory and visual receptive fields in the optic tectum of the barn
      owl (Tyto alba) is maintained through experience-dependent modification of
      auditory responses in the external nucleus of the inferior colliculus (ICX),
      which provides auditory input to the tectum. Newly learned tectal auditory
      responses, induced by altered visual experience, were found to be
      pharmacologically distinct from normal responses expressed at the same tectal
      sites. N-methyl-D-aspartate (NMDA) receptor antagonists administered systemically
      or applied locally in the ICX reduced learned responses more than normal
      responses. This differential blockade was not observed with non-NMDA or broad
      spectrum antagonists. Thus, NMDA receptors preferentially mediate the expression
      of novel neuronal responses induced by experience during development.

PMID- 8560272
TI  - [Various therapy concepts in severe fractures of the tibial pilon (type C
      injuries). A comparative study].
AB  - Between 1982 and 1992, 79 pylon fractures were treated with internal fixation as
      the primary treatment at the trauma department of the Hannover Medical School. In
      a retrospective study 71 patients were evaluated, and 51 of them were re-examined
      clinically and radiographically an average of 68 months after injury. The purpose
      of this study was to compare these different forms of surgical management
      concerning their long-term results: 1. Minimal invasive internal fixation for
      reconstruction of the joint with external transfixation of the ankle joint and/or
      plaster cast until bony healing occurred. 2. Primary internal fixation with
      plating of tibia and fibula following the AO techniques. 3. Internal fixation
      with a plate applied in a second step after initial reconstruction of the joint
      with minimal internal fixation and short-term external transfixation. Evaluation
      was based on the infection rate, the development of posttraumatic arthritis and
      the range of motion in the ankle joint as objective criteria. Subjective criteria
      were pain, swelling, and restrictions of working or leisure activities. Although
      only closed fractures were treated primarily by internal fixation with plating no
      significant differences between the three groups were found in the classification
      of fractures and soft tissue damage. All but 4 fractures were type-C lesions
      according to the AO classification, and 19 patients sustained open injuries. The
      infection rate for minimal invasive internal fixation was significantly lower
      with a two-step procedure (group 3) than with the one-step procedure according to
      a suitable statistic test (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8560273
TI  - [Quantitative follow-up of callus distraction with dual-energy roentgen
      absorptiometry (DEXA)].
AB  - With dual-energy X-ray absorptiometry (DEXA), bone mineralization during and
      after limb-lengthening procedures with unilateral fixators can be monitored
      quantitatively and precisely with low radiation exposure. We measured
      prospectively the bone mineral density (BMD) in the newly formed callus, in the
      bone adjacent to the callus and in the proximal femur in 21 patients with leg
      lengthening of the femur and/or tibia with unilateral external fixators.
      Mineralization showed a typical course with a peak value of 0.365 +/- 0.196 g/cm2
      (30.9% of the first value) at 6-8 weeks after the beginning of distraction and a
      minimum value at the time of maximum distraction. In the consolidation period BMD
      in the distraction gap increased to 1.020 +/- 0.234 g/cm2 (87%) at the time of
      fixation removal. BMD in the regenerated bone increased faster in regions of
      interest (ROIs) opposite the fixator compared to ROIs near it. Dynamization of
      the fixation device led to a 13% increase in mineralization velocity (VBMD). On
      the other hand, dynamization caused more homogeneous regeneration equalizing VBMD
      in the different ROIs as well. BMD in the proximal femur of the leg operated on
      decreased to 67% and in the contralateral leg to 87% of the preoperative value.
      We consider DEXA to provide a precise and quantitative assessment of callus and
      bone mineralization during limb lengthening with unilateral fixators. Since we
      are well aware of the limitation of the technique. DEXA helps to understand what
      is happening in limb-lengthening procedures by providing quantitative values.

PMID- 8560274
TI  - [Post-traumatic shoulder arthrodeses--indications, technique, results].
AB  - Shoulder arthrodesis definitely results in a restricted range of motion. However,
      in patients with a painful restricted motion after glenohumeral empyema or
      arthritis reduction of pain and an improved range of motion in the
      thoracoscapular joint are achieved with arthrodesis. Glenohumeral arthrodesis is
      also indicated for the management of paralysis of the rotator cuff if
      multidirectional stability is present. From 1978 to 1991 shoulder fusion was
      performed in ten patients in our institute. The mean age of the seven male and
      three female patients was 49 years. In six cases arthrodesis was necessary
      because of shoulder infections after internal fixation of humeral head fractures;
      three were performed because of posttraumatic arthritis and two, because of
      complete plexus lesions. The followup an average of just over 3 years after
      arthrodesis revealed acceptable function according to the Neer and Hawkins score.
      All patients but one reported a significant improvement of function and pain
      relief after arthrodesis.

PMID- 8560275
TI  - [Biomechanical studies of human Achilles tendon rupture].
AB  - The biomechanical properties of human Achilles tendon are described with a
      computer-controlled material-testing machine. With an optimized fixation device
      for the muscle-tendon-calcaneus system the rupture was intratendineal. The
      tendons were compared for different rupture speed (1000 mm/min vs 100 mm/min),
      sex and age ( < 35 years vs > 35 years). The tendons ruptured at 1000 mm/min had
      better results in terms of maximum rupture force, stiffness and tensile stress,
      while the results for elongation and energy were less good. None of these
      differences were statistically significant. Significant differences were found
      between the sexes: male tendons had higher maximum rupture force and stiffness
      and a larger cross-sectional area. In the younger tendons significantly higher
      tensile rupture stress and lower stiffness were found.

PMID- 8560276
TI  - [Diagnosis and spontaneous course of non-traumatic localized myositis
      ossificans].
AB  - Non-traumatic localized myositis ossificans is a rare variant of pseudotumoral
      muscular ossification. In the early stage it may be misdiagnosed as soft tissue
      sarcoma or some kind of osteosarcoma. Myositis ossificans itself does not always
      require therapy; when diagnosed on the basis of the typical features revealed by
      meticulous non-invasive investigation, biopsy is not mandatory for confirmation
      of the diagnosis. The diagnostic procedures needed - radiography, ultrasound,
      MRI, and isotope bone scan - are discussed with reference to three clinical case
      reports.

PMID- 8560277
TI  - [Intraoperative EMG recording in stimulation of the glenohumeral joint capsule].
AB  - In an experimental study we investigated the EMG response in 10 patients after
      intraarticular stimulation of the joint capsule. Intraoperative stimulation was
      achieved by arthroscopic placement of the stimulation catheter at the anterior
      joint capsule. The muscle response was documented by mono- or bipolar electrodes.
      We found reproducible EMG muscle responses in both superficial and deep muscle
      layers. The response time was between 100 and 516 ms. The shortest muscle
      response was found at the anterior part of the deltoid muscle and the longest at
      the supraspinatus muscle and the lateral part of the deltoid muscle.

PMID- 8560278
TI  - [Quality assurance in trauma surgery].

PMID- 8560279
TI  - [Development of a practice-oriented curriculum. 9. Arthrology].
AB  - The background problem this article addresses is the need to reduce the quantity
      of medical information to a standard core of knowledge relative to the
      overwhelming amount of scientific information to be learned in the limited amount
      of time students have available. The article is part of a study the aim of which
      is to define a core students, independent of their further medical
      specialization. The design of this study is a survey of a representative sample
      of Swiss general practitioners who were asked to identify in the list of Nomina
      Anatomica the most prevalent anatomical entities (terms) occurring in their
      practice. To assure the representativeness of the sample the identified terms
      were compared to prevalent diagnoses of all Swiss general practitioners and to
      the incidence of cases in German hospitals. From the list of International
      Anatomical Nomenclature (IANC) 280 anatomical terms could be identified with
      respect to arthrology. Of these, 250 were judged uniformly by the physicians: 52
      terms were considered relevant, while it was not though necessary for 198 terms
      to be relevant, while it is was not thought necessary for 198 terms to be
      learned, i.e. general practitioners agreed on 89.3% of the terms. Only 29.7% of
      the terms in the IANC list belong to anatomical core knowledge in arthrology.
      There is evidence for the representativeness of these findings when compared to
      the prevalence of diagnoses made by general practitioners and to the incidence of
      cases in German hospitals. The method of using criteria of prevalence in a survey
      to identify a core of knowledge in medicine is suited for the definition of
      learning content necessary for professional purposes.

PMID- 8560280
TI  - [Overview, analysis and evaluation of the 1995 public health structural law and
      the federal social care law from the viewpoint of the trauma surgery department
      of a university clinic. Measures for preparation of a new reimbursement system
      and documentation requirements].
AB  - All doctors in Germany are required to cooperate in the implementation of the
      health system reform and the new system for reimbursement of the hospitals to
      limit the negative consequences to the patients. It would be absolutely wrong to
      leave the medical services of the insurance companies to define the diagnosis
      related groups and determine the charges. The revision of the health system is
      beneficial in that it supports the economical independence of hospital
      departments. It is a good idea for them to be paid by results; however, there are
      no established methods of measuring results or efficacy in medicine. Germany is
      about 10 years behind the USA in this, so that our country is not yet ready for
      this reform. Hospital departments do have the freedom to make economic decisions,
      being heavily dependent on the insurances and the government, because most people
      who work in hospital are paid from these sources. Departments of trauma or
      orthopaedic surgery are disadvantaged by the reform, because of the number and
      kind of diagnosis related groups and the method of reimbursement. This leads to a
      profit-oriented system of medical documentation, with possible upcoding of
      diagnoses in future. The present health reform most probably will not increase
      the efficiency of hospitals; it will not be possible to attain cost reductions
      with the same level of medical care. The reduced reimbursement will force doctors
      to cut down their expenses and restrict diagnostic and therapeutic procedures. On
      the other hand the administration sector in hospitals and insurances will expand
      dramatically in future.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8560281
TI  - Introduction: management of thalassemia.

PMID- 8560282
TI  - Prevention of beta-thalassemia major and Hb Bart's hydrops fetalis syndrome.

PMID- 8560283
TI  - The management of patients with Cooley's anemia: transfusions and splenectomy.

PMID- 8560284
TI  - Management of thalassemias: growth and development, hormone substitution, vitamin
      supplementation, and vaccination.

PMID- 8560285
TI  - Transfusion-dependent thalassemia: viral complications (epidemiology and follow
      up).

PMID- 8560286
TI  - Management of cardiac complications in patients with thalassemia major.

PMID- 8560287
TI  - Bone marrow transplantation in thalassemia.

PMID- 8560288
TI  - Chelation therapy in beta-thalassemia: the benefits and limitations of
      desferrioxamine.
AB  - In summary, long-term studies of DFO therapy in multiply-transfused patients with
      beta-thalassemia major have clearly shown it to be generally safe and effective.
      Appropriate use of DFO can remove excess iron, prevent iron-induced organ damage,
      and improve survival in thalassemia patients. Patients who begin treatment at a
      young age can be protected from the lethal complications of iron overload for at
      least two decades, but chelation therapy may not always prevent or ameliorate
      late growth failure and/or delayed or absent puberty. Those with iron damage to
      the heart and possibly other organs may experience stability or improvement in
      function with intense chelation. High-dose intravenous DFO produces a rapid
      decrease in hepatic iron content and improved cardiac function but can also cause
      severe toxicity, as can normal doses in patients with a low iron burden.
      Continuing studies of DFO are necessary to help further define its long-term
      efficacy and toxicity. In particular, significant attention should be paid to new
      strategies aimed at fostering improved compliance with its use.

PMID- 8560289
TI  - Periconceptional folic acid supplementation as a social intervention.
AB  - Periconceptional folic acid supplementation has been shown to decrease the first
      occurrence of isolated neural tube defects (NTDs) by as much as 50%, and to
      decrease the recurrence risk for NTDs by more than 70%. The possible mechanisms
      of vitamin supplementation in the prevention of NTDs are discussed, as are the
      current recommendations for reproductive-age women. Further, the limitations of
      dietary and pharmacological recommendations with regard to patient compliance as
      well as the possibility of grain fortification are reviewed.

PMID- 8560290
TI  - Preterm birth in the African-American community.
AB  - Preterm births account for a substantial portion of infant mortality, the major
      difference in mortality between African-American and white births in the United
      States, and the key reason that US infant mortality exceeds that of other
      developed nations. Although preterm birth rates are higher in the African
      American community for certain known reasons (proportionately more unwanted
      conceptions, poorer nutrition, less sufficient prenatal care, and stress
      associated behavioral risks), most of the excess risk for preterm delivery
      remains unexplained. Because preterm delivery is poorly understood in general,
      prevention strategies are limited. Future research directions should explore
      contextual and social conditions that might be altered to reduce preterm births
      in the African-American community.

PMID- 8560291
TI  - Home visits during pregnancy: consequences on pregnancy outcome, use of health
      services, and women's situations.
AB  - This review of eight randomized controlled trials assessed two different types of
      home visits during pregnancy: (1) those offering social support to high-risk
      women; and (2) those providing medical care to women with complications. In both
      categories, pregnancy outcome was not improved when women received home visits.
      The summary odds ratio for preterm delivery (< 37 weeks) was 1.0 (95% CI: 0.8 to
      1.1). Nor did the home visits decrease the rate of hospital admission for women
      with complications (mainly threatened preterm labor or toxemia); the
      corresponding summary odds ratio was 0.9 (95% CI: 0.7 to 1.2). Nevertheless in
      some trials home visits had positive effects on women (medical knowledge, support
      levels, health habits, and satisfaction). The randomized controlled trials
      provide little evidence that programs offering home visits are effective in
      improving either pregnancy outcome or the use of health services. A better
      integration of hospital and home services might allow a more rational use of
      health services for women with complications. In addition, we need to define more
      precisely the content of home visits providing social support. For this, further
      research is required on how emotional support, health education, and advice
      influence the health of women and infants and mother-child interactions.

PMID- 8560292
TI  - Working conditions, maternity legislation, and preterm birth.
AB  - The review of the scientific literature on the role of employment-related
      physical activity suggests that prolonged standing and long working hours may
      increase the risk of preterm delivery. Although maternity legislation in many
      European countries has regulated work schedules and working conditions for
      pregnant women, none of the European countries except for France seems to have
      experienced a reduction in preterm rates. France has had both a comprehensive
      maternity legislation and a national program specifically aimed to reduce preterm
      birth. Despite the lack of reduction in preterm rates, paid maternity leave,
      guaranteed job protection, and regulation of hazardous working conditions remain
      a desirable societal goal for any industrialized nation.

PMID- 8560293
TI  - Smoking cessation interventions for pregnant women: review and future directions.
AB  - A substantial proportion of disease and death in the US could be prevented if
      tobacco use was curtailed or eliminated. Low birth weight, pregnancy
      complications, and infant morbidity are but a few of the adverse outcomes
      experienced by pregnant and postpartum women and infants that result from
      cigarette smoking. Pregnancy may be an ideal time to intervene with smoking
      women. On learning of their pregnancy, many women reduce or quit smoking on their
      own. For those who do not quit, interventions during the childbearing year could
      provide additional incentive and support for complete cessation. Successful
      clinic-based interventions share similar characteristics and tailoring cessation
      messages to client populations may enhance the effectiveness of interventions.
      Assessing a smoker's degree of addiction and tailoring counseling for cessation
      according to the patient's readiness might enhance current clinical practices.
      Even with the most effective individual counseling, it is increasingly evident
      that additional strategies are needed to achieve population-wide reductions in
      smoking and its related health conditions. Examples of these efforts are
      increased taxation on cigarettes, community-based anti-tobacco programs, and
      increasing the number of smoke-free environments. Thus, in addition to clinic
      based efforts, health professionals might take an active role in supporting the
      broad range of programmatic, legislative, and advocacy efforts.

PMID- 8560294
TI  - Identification and care of problems associated with alcohol ingestion in
      pregnancy.
AB  - Fetal alcohol syndrome (FAS) and alcohol-related birth defects (ARBD) are fully
      preventable if alcohol use is separated from pregnancy. However, accomplishing
      this can be much harder than it might seem. This article describes some
      strategies for identification and treatment of women who drink during pregnancy.

PMID- 8560295
TI  - Cocaine using during pregnancy and low birth weight: the impact of prenatal care
      and drug treatment.
AB  - Cocaine use in pregnancy has been associated with low birth weight. Large
      population-based studies suggest that 5 to 7% of pregnant women have used
      cocaine, with much higher rates in low income inner-city women. Among 140 births
      at our institution of cocaine-using women, we found a lower rate of low birth
      weight in those who received prenatal care compared with those without prenatal
      care: 33 of 96 (34.3%) versus 23 of 44 (52.3%), P < .05. A review of the
      literature shows that comprehensive care, which includes both prenatal care and
      drug treatment, seems to be associated with better birth weight outcomes,
      particularly in women who stop their use in the first trimester. Prenatal care
      alone, however, is also associated with improved outcomes even if not specialized
      or linked to drug treatment.

PMID- 8560296
TI  - Addressing battering during pregnancy: reducing low birth weight and ongoing
      abuse.
AB  - It has been established that battering during pregnancy is a frequently occurring
      and significantly deleterious phenomena. This article reviews the evidence
      regarding dynamics, prevalence, outcomes, and cultural and other influences on
      this issue. Although tested interventions for abuse during pregnancy are limited,
      there are clear indications from research with other battered women for
      directions to be taken.

PMID- 8560297
TI  - Enhancing perinatal outcome in homeless women: the challenge of providing
      comprehensive health care.
AB  - Homeless women who are pregnant present a number of challenge to health care
      providers. As a group, they are at risk for a variety of illnesses that could
      affect their pregnancies, including sexually transmitted diseases and substance
      abuse. Poor access to health care, inadequate prenatal care, poor nutrition, and
      poor housing cause these women to suffer poor birth outcomes. They are more
      likely to deliver low birth weight infants and have higher rates of infant
      mortality. It should be understood that homeless pregnant women are a
      heterogenous group. Generally, they are pregnant adolescents and women in
      homeless families. Additionally, there are differences within these two groups.
      The causes of homelessness for these women vary as do their needs during
      pregnancy. Any provider of health care to the homeless must understand the
      different situations of these women to deliver directed, effective care.

PMID- 8560298
TI  - Pregnancy behind bars.
AB  - Since the 1960s, the cycle of violence and drug use has mounted and an increasing
      number of people are being incarcerated. Coincident with this phenomena, we have
      experienced rising rates of morbidity and mortality among the incarcerated, many
      of whom suffer from infectious diseases. In fact, the spread of diseases like
      tuberculosis has been facilitated by the congregate nature of the penal system.
      As the number of people behind bars has risen, we have seen a disproportionate
      increase in the number of women incarcerated, most of whom are in their
      childbearing years. The number of pregnant women in jails and prisons has, in
      turn, been escalating. Certain prenatal interventions are described and evaluated
      in the literature, which we review in this article. Experience with the prenatal
      program in the New York City jail system is described. In general, the authors'
      position is that as society chooses a social policy of incarceration to address
      the problems of violence and drug use, there is solid public health reason to
      design and implement comprehensive prenatal programs in correctional facilities
      with connections to community-based health services.

PMID- 8560299
TI  - Social interventions in the care of human immunodeficiency virus (HIV)-infected
      pregnant women.
AB  - The incidence of infection with the human immunodeficiency virus (HIV) is
      increasing among women of childbearing age. Women now account for 18% of the
      total number of cases of the acquired immunodeficiency syndrome (AIDS), compared
      with 9% a decade ago. The medical care of pregnant HIV-infected women must take
      into account the high prevalence of substance abuse, preceded and often
      accompanied by significant levels of physical, emotional, and sexual trauma, and
      the concomitant stigmatization of these women in their families and communities.
      Pregnancy is often a time when women are motivated to make major positive
      behavioral and life-style changes. To do this, they need ongoing,
      multidisciplinary counseling and support, with recognition that progress may be
      intermittent and slow. The Special Prenatal Care Program at Bellevue Hospital is
      described to show the level of resource commitment that is needed as well as the
      nearly universal acceptance of voluntary HIV counseling and testing in these
      conditions. Trends in permanency planning for the children of HIV-infected women
      are described. Future research needs are outlined, including female-specific drug
      treatment and more effective contraceptive technology for both men and women.

PMID- 8560300
TI  - Preventive interventions with low birth weight premature infants: an evaluation
      of their success.
AB  - The outcome literature on low birthweight (LBW) premature children indicates that
      they are at risk for a variety of neurodevelopmental impairments throughout
      childhood. To prevent such disabilities, numerous interventions have been
      initiated with LBW children. Nineteen intervention programs designed for LBW
      preterms that have published study results dating from 1971 are reviewed.
      Included are interventions in the neonatal nursery, at home, and at centers as
      well as interventions that are both child-focused and parent-focused. One
      randomized clinical trial evaluating comprehensive intervention services, the
      Infant Health and Development Program, is described in detail. Conclusions from
      the studies reviewed indicate that intervention programs have had only modest
      success in altering neurodevelopmental outcomes, although parent-child
      interaction has often been facilitated. Future research on the effects of
      preventive intervention needs to examine long-term developmental competencies and
      to replicate positive findings in multiple settings.

PMID- 8560301
TI  - Developing outcome measures for ambulatory care--an application to asthma and
      diabetes.
AB  - Increasing emphasis is now being placed on the assessment of patient outcomes,
      both in evaluating medical interventions and in quality assurance initiatives.
      Clinicians, purchasers, managers and researchers need outcome measures that are
      valid, reliable and responsive. This paper describes the theory and practice
      underlying the development of outcome measures for two chronic conditions, asthma
      and diabetes, for application in ambulatory settings. Existing generic and
      condition-specific health status and health-related quality-of-life measures were
      administered to almost 1300 patients. The psychometric properties of these
      measures were examined to identify those that were of adequate validity and
      reliability in these population groups. Step-wise regression procedures were then
      used to identify a core set of scales that best predicted patients' general
      health perceptions, which could be used in measuring general health outcomes for
      each of these groups. These core sets consist of up to 40 items, spanning
      physical function, energy and vitality, emotional well-being and condition
      specific aspects of health such as symptom control. Further analysis is being
      carried out to assess the responsiveness to change of these core item sets.

PMID- 8560302
TI  - The Swedish SF-36 Health Survey--I. Evaluation of data quality, scaling
      assumptions, reliability and construct validity across general populations in
      Sweden.
AB  - We document the applicability of the SF-36 Health Survey, which was translated
      into Swedish using methods later adopted by the International Quality of Life
      Assessment (IQOLA) Project procedures. To test its appropriateness for use in
      Sweden, it was administered through mail-out/mail-back questionnaires in seven
      general population studies with an average response rate of 68%. The 8930
      respondents varied by gender (48.2% men), age (range 15-93 years, mean age 42.7),
      marital status, education, socio-economic status, and geographical area.
      Psychometric methods used in the evaluation of the SF-36 in the U.S. were
      replicated. Over 90% of respondents had complete items for each of the eight SF
      36 scales, although more missing data were observed for subjects 75 years and
      over. Scale scores could be computed for the vast majority of respondents (95%
      and over); slightly fewer in the oldest subgroup. Item-internal consistency was
      consistently high across socio-demographic subgroups and the eight scales. Most
      reliability estimates exceeded the 0.80 level. The highest reliability was
      observed for the Bodily Pain Scale where all subgroups met the 0.90 level
      recommended for individual comparisons; coefficients at or above 0.90 were also
      observed in most subgroups for the Physical Functioning Scale. Tests of scaling
      assumptions including hypothesized item groupings, which reflect the construct
      validity of scales, were consistently favorable across subgroups, although lower
      rates were noted in the oldest age group. In conclusion, these studies have
      yielded empirical evidence supporting the feasibility of a non-English language
      reproduction of the SF-36 Health Survey. The Swedish SF-36 is ready for further
      evaluation.

PMID- 8560303
TI  - German translation and psychometric testing of the SF-36 Health Survey:
      preliminary results from the IQOLA Project. International Quality of Life
      Assessment.
AB  - International translation and psychometric testing of generic health outcome
      measures is increasingly in demand. Following the methodology developed by the
      International Quality of Life Assessment group (IQOLA) we report the German work
      with the SF-36 Health Survey. The form was translated using a forward-backward
      method with accompanying translation quality ratings and pilot tested in terms of
      translation clarity and applicability. Psychometric evaluation included
      Thurstone's test of ordinality and equidistance of response choices in 48
      subjects as well as testing of reliability, validity, responsiveness and
      discriminative power of the form in crossectional studies of two samples of
      healthy persons and longitudinal studies of two samples of pain patients
      totalling 940 respondents. Quality ratings of translations were favorable,
      suggesting a high quality of both forward and backward translations. In the pilot
      study, the form was well understood and easily administered, suggesting high
      clarity and applicability. Thurstone's test revealed ordinality (in over 90% of
      the cases) and rough equidistance of response choices also as compared to the
      American original. On item and scale level, missing data were low and descriptive
      statistics indicated acceptable distribution characteristics. In all samples
      studied, discriminative item validity was high (over 90% scaling successes) and
      Cronbach's alpha reliabilities were above the 0.70 criterion with exception of
      one scale. Furthermore convergent validity, responsiveness to treatment and
      discriminative power in distinguishing between healthy and ill respondents was
      present. The preliminary results suggest that the SF-36 Health Survey in its
      German form may be a valuable tool in epidemiological and clinical studies.
      However further work as concerns responsiveness and population based norms is
      necessary.

PMID- 8560304
TI  - Quality of life in chronic fatigue syndrome.
AB  - Whilst the debilitating fatigue experienced in patients suffering from Chronic
      Fatigue Syndrome (CFS) results in a subjective marked impairment in functioning,
      little research has investigated the impact of this disorder on quality of life.
      Forty-seven subjects with a confirmed diagnosis of CFS and 30 healthy controls
      were compared using the Sickness Impact Profile (SIP). A subgroup of subjects
      were interviewed regarding the impact CFS has had on their social and family
      relationships, work and recreational activities. Results from both the SIP and
      the interview revealed that CFS subjects had significantly impaired quality of
      life, especially in areas of social functioning. These findings highlight the
      importance of addressing the social isolation and loss of role functioning
      experienced by CFS sufferers.

PMID- 8560305
TI  - Environmental and health-related quality of life: conceptual and methodological
      similarities.
AB  - The recent revival of interest in the concept of quality of life by academics in
      both the social and medical sciences, and amongst politicians has focused
      attention on the continuing debate about the definition, measurement and
      utilisation of quality of life. In particular, the need amongst regulatory and
      financial authorities--both in the health sector and in local government--to know
      about the potential impact of intervention has encouraged further interest in the
      use of quality of life measures to assist resource allocation and assessing the
      impact of policy decisions. In this paper it is argued that whilst such measures
      may be the ultimate goal of research, this can only be constructed on a fuller
      understanding of quality of life measures of current conditions and the
      relationship between components of life quality. A conceptual framework is
      developed to show the relationship between the way that quality of life, in both
      environmental and health-related studies, has been conceived and measured. The
      strong similarities in both respects are discussed, pointing to the need for
      heightened interdisciplinary dissemination of research methods and assessments.

PMID- 8560306
TI  - Clinical and public health perspectives and applications of health-related
      quality of life measurement.
AB  - Health-related quality of life (HRQL) measures have been developed from the
      utilitarian ethical perspective of public health medicine which may be contrasted
      with individual-centered indicators; these emphasise the unique experience of a
      patient. The impairment-disability-handicap framework provides a more complete
      description of disease consequences and health outcomes than a generic HRQL
      indicator. The assessment of reliability and validity of HRQL indicators is often
      carried out inappropriately: population repeatability is measured when an
      indicator will be used to examine changes in individuals; between observer
      variation may be large compared with variation between populations. Content and
      construct validity are usually measured but the more important predictive
      validity is neglected. Effect sizes of HRQL indicators are likely to be inflated
      by use of between subject estimates of variance but the more appropriate within
      subject variance is seldom reported. HRQL indicators are of very limited value
      for many clinical and public health tasks: monitoring health of individuals and
      populations; evaluating the effects of health and social policy; allocating
      resources; evaluating the effects of treatment. Alternative methods of assessment
      derived from the impairment-disability-handicap conceptual framework are
      preferable.

PMID- 8560307
TI  - Evaluating the efficacy of medical treatment: possibilities and limitations.
AB  - This review outlines the possible uses of subjective health status measures in
      the evaluation of medical treatment, and possible limitations and pitfalls that
      potential users of such measures must be aware. Whilst much has been written
      about the requirements of measures in terms of reliability, validity and
      responsiveness, many existing measures which have gained widespread use have
      serious shortcomings. In this paper, the limitations of some existing
      questionnaires are outlined. It is argued that whilst outcomes measurement has
      the promise to positively influence medical care, done without due consideration
      of its limitations and weaknesses it could lead to inaccurate or inappropriate
      data. In the current climate, in which health outcomes data is viewed as central
      to monitoring and evaluation, inappropriate or unconsidered use of measures could
      have drastic effects.

PMID- 8560308
TI  - The World Health Organization Quality of Life assessment (WHOQOL): position paper
      from the World Health Organization.
AB  - This paper describes the World Health Organization's project to develop a quality
      of life instrument (the WHOQOL). It outlines the reasons that the project was
      undertaken, the thinking that underlies the project, the method that has been
      followed in its development and the current status of the project. The WHOQOL
      assesses individuals' perception of their position in life in the context of the
      culture and value systems in which they live and in relation to their goals,
      expectations, standards and concerns. It has been developed collaboratively in
      several culturally diverse centres over four years. Piloting of the WHOQOL on
      some 4500 respondents in 15 cultural settings has been completed. On the basis of
      this data the revised WHOQOL Field Trial Form has been finalized, and field
      testing is currently in progress. The WHOQOL produces a multi-dimensional profile
      of scores across six domains and 24 sub-domains of quality of life.

PMID- 8560309
TI  - Health-related quality of life between naturalism and hermeneutics.
AB  - Interest in measuring Quality of life (QOL) in modern medicine has increased
      considerably in recent years. However, there is no generally agreed definition of
      QOL, but the term encompasses several constructs, including physical, functional,
      emotional, social and cognitive domains. A psychometric approach is typically
      applied, but major problems conceptual confront this tradition. It is argued that
      QOL research follows a naturalistic tradition in medicine, and that the
      theoretical status of the QOL concept remains ambiguous. Hence, the more neutral
      term multidimensional evaluation is suggested as more appropriate than QOL.
      Hermeneutic thinking with its focus on meaning, understanding and interpretation
      of the individual placed in a historical and social context is briefly introduced
      and its role for QOL discussed. A radical hermeneutic position focusing solely on
      the subjectivity of the individual is rejected, and a balanced view is suggested.
      Such a view should not ignore that man is a biological organism which can be
      subjected to naturalistic studies, but it should also take into account those
      features which constitutes man as a person, e.g. understanding and
      interpretation. Future QOL research may benefit from an integration of
      philosophical reflection on health and disease issues and a psychometric
      tradition.

PMID- 8560310
TI  - A QALY-based societal health statistic for Canada, 1985.
AB  - This paper assesses the appropriateness of QALYs (quality adjusted life years) as
      a foundation for an index of societal health, and the feasibility of using such
      an index to guide health care policy. Results of this paper suggest that the
      standard aggregate QALY index imposes an ethical position on policy makers which
      may promote inequality in well-being associated with health. It is possible to
      rectify this problem in theory, but current data are insufficient to estimate
      such corrected indices. A QALY-based index, constructed using the best available
      data, indicates morbidity has a significant effect on Canadian health status
      (e.g. life expectancy figures alone overstate community health by about 10%),
      that the impact of morbidity is unequal across regions and gender, and that role
      (the ability to fulfil social functions) and mobility dysfunction are important
      determinants of ill-health in this population.

PMID- 8560312
TI  - Elderly people's definitions of quality of life.
AB  - The subject of this paper is the definition and measurement of the concept of
      quality of life, and questions the operationalization of quality of life simply
      in terms of health status measures and scales of functional ability. It is based
      on a review of the literature, and the initial analyses of the first stage of a
      study designed to identify individual's views of the quality of their lives and
      to test the relevance of various scales used to measure quality of life. The
      study focuses on older people living at home in two contrasting areas of south
      east England, and demonstrates not only that older people can talk about, and do
      think about, quality of life, but also highlights how quality of life varies for
      different age groups of the elderly population living at home, in different
      geographical areas. In addition, early conclusions also indicate that there is
      more to quality of life than health; indeed, social contacts appear to be as
      valued components of a good quality of life as health status. This study deals
      with issues high on the agenda of the current debate on quality of life and its
      measurement; it has implications for those involved in both quality of life
      research and in health and social service policy for older people.

PMID- 8560311
TI  - Maximizing health benefits vs egalitarianism: an Australian survey of health
      issues.
AB  - Economists have often treated the objective of health services as being the
      maximization of the QALYs gained, irrespective of how the gains are distributed.
      In a cross section of Australians such a policy of distributive neutrality
      received: (a) very little support when health benefits to young people compete
      with health benefits to the elderly; (b) only moderate support when those who can
      become a little better compete with those who can become much better; (c) only
      moderate support when smokers compete with non smokers; (d) some support when
      young children compete with newborns; and (e) wide spread support when parents of
      dependent children compete with people without children. Overall, the views of
      the study population were strongly egalitarian. A policy of health benefit
      maximization received very limited support when the consequence is a loss of
      equity and access to services for the elderly and for people with a limited
      potential for improving their health.

PMID- 8560313
TI  - What things are important in people's lives? A survey of the public's judgements
      to inform scales of health related quality of life.
AB  - The research presented here aimed to obtain population norms on pertinent domains
      of quality of life and health related quality of life, and the relative
      importance of these domains to people. The OPCS Omnibus Survey was used as the
      vehicle for the study. This is a monthly survey of a random sample of 2000 adult
      members of the population in Great Britain, based on a random sample of
      households. The data was collected for a one month period. The response rate to
      the survey was 77%. In response to a generic question about the five (priority
      ordered) most important things in their lives (good or bad), respondents were
      most likely to freely mention as the first most important thing in their lives
      relationships with family or relatives, followed by their own health, the health
      of another (close) person and finances/standard of living/housing. When responses
      relating to respondents' priority ranked areas 1-5 were combined, the most
      frequently mentioned area of life was finances/standard of living/housing,
      followed by relationships with family and friends, own health, the health of
      close others and social life/leisure activities. Thus, different distributions
      were obtained depending on whether priority ordering or frequency with which item
      was mentioned was analysed. Of those who reported a longstanding illness, the
      conditions which were most likely to be reported as affecting their lives were
      respiratory conditions, joint disorders and heart and circulatory diseases. The
      most commonly freely mentioned first most important effects of the longstanding
      illness on their lives were (in order of frequency) ability to get out and
      about/stand/walk/go out shopping, being able to work/find a job and effects on
      social life/leisure activities (based on office coding from verbatim responses
      recorded on the questionnaire). When the responses relating to respondents'
      priority ranks 1-5 were combined, the most frequently mentioned area of life
      affected was ability to get out and about/stand/walk/go out shopping, followed by
      social life/leisure activities, and availability of work/ability to work. Again,
      differences in distributions were obtained depending on the method of analysis.
      Further investigations also revealed differences according to the method of
      questioning and coding (respondent vs office). When respondents selected their
      own codes from a showcard in relation to health effects, there were some
      discrepancies with their (office coded) verbatim replies (which were recorded by
      the interviewer before they saw the showcard, for later office coding). The
      showcard had the effect of prompting them, and the then most commonly mentioned
      first most important effects of the longstanding illness on their lives were (in
      order of frequency) pain, tiredness/lack of energy/lethargy, social life/leisure
      activities, and availability of work/ability to work. This discrepancy
      illustrates the biasing influence of using showcards, in comparison with the open
      coding of actual verbatim responses back in the office (on the assumption that
      the latter are more valid-unprompted-responses). Analysis of the domains included
      in the most popularly used health status scales, which are used to measure health
      related quality of life, revealed that several items ranked as important by the
      public were missing.

PMID- 8560314
TI  - Quality of life assessment in pediatric oncology: a retrospective review of phase
      III reports.
AB  - BACKGROUND: although the quality of life of cancer patients has been a topic of
      increasing interest, the research literature to date has generally noted minimal
      reporting of these data in adult clinical trials. PURPOSE: the purpose of this
      investigation was to examine the frequency with which these measures are reported
      in pediatric cancer clinical trials. METHOD: published reports of 70 Phase III
      clinical trials from the Pediatric Oncology Group and Childrens Cancer Group were
      reviewed for presentation of quality of life and toxicity data. RESULTS:
      approximately 3% of these reports included quality of life data, while toxicities
      were noted for over 75% CONCLUSIONS: quality of life endpoints are not reflected
      in clinical trial reports. Education as to the potential usefulness of these
      data, as well as recognition of the barriers that exist to using such measures
      must be addressed.

PMID- 8560315
TI  - Substance abuse-affected families in the child welfare system: new challenges,
      new alliances.
AB  - During the past decade a record number of single-parent families entered the
      child welfare system because the mother had an identified problem of substance
      abuse. These trends have forced child welfare agencies and substance abuse
      treatment providers to take a new look at the needs of mothers with problems of
      chemical dependency and their children. This article examines the issues that
      face child welfare and substance abuse treatment professionals as they attempt to
      address these new challenges and recommends strategies for forging new alliances
      and closing gaps in service delivery. The article calls for action to end the
      oppression that hampers efforts to effectively serve these families.

PMID- 8560316
TI  - Beneficence re-examined: protective intervention in mental health.
AB  - Social workers have long reacted negatively to the idea of limiting client
      freedoms, seeing such activity as directly contrary to such central social work
      values as autonomy and self-determination. Nevertheless, practitioners often find
      themselves required to actively intervene in a protective manner when clients are
      unable to fend for themselves. Such interventions are increasingly a part of
      everyday practice as social workers respond to new mandates to provide services
      to disabled and vulnerable individuals. Because of these changing circumstances,
      the concept of beneficence and the process of protective treatment are currently
      being re-examined, especially in mental health. This article develops a
      conceptual model of protective intervention that can be used by clinical decision
      makers in a variety of situations. Case examples drawn from work with chronically
      mentally ill patients are used to illustrate the discussion.

PMID- 8560317
TI  - Supporting patient autonomy: decision making in home care.
AB  - This study examines the policies and procedures that home health care agencies
      have developed to handle the incapacitated patient and life-sustaining treatment
      decisions. Data collected from a survey of 154 home health care agency directors
      and interviews with 92 local agency staff (including nurses and social workers)
      and 67 patients confirmed that directors, staff, and patients agree that patients
      are informed about their legal rights. When asked about specific rights, fewer
      patients were aware of their right to execute an advance directive, and even
      fewer patients had actually executed one. Only 67 percent of agencies reported
      having existing policies on advance directives and life-sustaining treatment
      decisions, whereas 41.5 percent had policies on how to handle the patient with
      questionable decision-making capacity. Consistent policies are needed for social
      workers, nurses, and other staff to handle such difficult ethical dilemmas. A
      review of specific agency policies is presented with recommendations for future
      policy changes and development.

PMID- 8560318
TI  - Research responds: monitoring the impact of social legislation.

PMID- 8560319
TI  - Fear of AIDS and homophobia: implications for direct practice and advocacy.
AB  - Studies of health care trainees and professionals have demonstrated that their
      level of empathy and caring is negatively affected by the knowledge that the
      person being treated is homosexual, in part because of stigma associated with HIV
      infection and AIDS. The survey discussed in this article examined the
      relationship between homophobia and the fear of AIDS within the context of
      several categorical questions. Gender differences in attitudes were also
      examined. Respondents who more liberally endorsed rights for gay men and lesbians
      were less homophobic and had less fear of AIDS. Suggestions are made for
      sensitizing social workers to the inhibitory effects of homophobia and fear of
      AIDS when working with HIV-infected clients or people in the gay community.

PMID- 8560320
TI  - Asymmetrical role-taking: comparing battered and nonbattered women.
AB  - Franks's social psychological model of oppressive situations and asymmetric role
      taking offers a new way of understanding the predicaments faced by battered
      women. Unlike individualistic or single-factor explanations, the model suggests
      that women faced with a particular combination of situational pressures and
      relationship inequities are especially vulnerable to distressful emotions and
      self-esteem difficulties. Survey data from 66 battered women using domestic
      violence services and 80 nonbattered women were collected to test the major
      propositions of the model. Battered women's social situations were oppressive and
      characterized by powerlessness, social isolation, and economic dependency.
      Batterers were poor empathizers. Predictions about self-blame and identification
      with the aggressor were not confirmed. The practical value of this theoretical
      approach with its emphasis on enhancing women's power base and increasing men's
      interpersonal sensitivity is developed.

PMID- 8560321
TI  - People with disabilities and social work: historical and contemporary issues.
AB  - From the earliest recorded history, people with disabilities have been
      ostracized, rejected, and discriminated against in society. Although social work
      has a history rich in advocacy for oppressed people, the profession has been
      hesitant to become involved with people with disabilities. This article addresses
      historical and contemporary issues concerning disability. Recent developments in
      the disability movement, including independent living, are discussed and compared
      to social work's approaches to disability. Finally, a plea is made to the social
      work profession and the disability movement to combine efforts to enhance the
      lives of people with disabilities.

PMID- 8560322
TI  - Pathways of older adolescents out of foster care: implications for independent
      living services.
AB  - This article reports the results of a study of final discharge outcomes for an
      exit cohort of 2,653 foster youths in California who were at least 17 years old
      at exit and had spent at least 18 months in care before their final discharge. A
      logistic regression model of discharge status was developed that expresses the
      effect of selected variables on the odds that a child exited foster care via one
      of three routes: (1) by reaching the age of majority while still in care or being
      legally emancipated to independent living; (2) by family reunification, placement
      with a relative or guardian, or adoption; or (3) by an "unsuccessful" exit from
      care. A youth's number of placements in foster care, time spent in care, and the
      type of placement the child last resided in were all found to be related to final
      discharge status. The implications of these findings for efforts to prepare
      foster youths for independent living are discussed. Of particular interest is the
      finding that a large proportion of youths who have spent a long time in foster
      care away from their families nevertheless return to their families at exit from
      care.

PMID- 8560323
TI  - A closer look at self-image in male foster care adolescents.
AB  - Using the Offer Self-Image Questionnaire, this study attempted to determine the
      differences between 58 male adolescents in foster care and their peers in the
      normal population and to establish if there are characteristics of the
      adolescents' background or foster care experience related to specific domains of
      self-image. Characteristics from foster care history included number of
      placements and length of time at the current placement. Individual background
      characteristics included race, educational achievement, and age. Foster care
      youths had lower family self-image and emotional health and higher social self
      image when compared with the normative population. Lower scores on several
      domains of self-image were associated with being younger, being white, having
      lower academic achievement, having more placements, and staying at the current
      placement for a longer time. The implications of these findings for foster care
      placement decisions are discussed.

PMID- 8560324
TI  - Understanding the social needs of streetwalking prostitutes.
AB  - The social dynamics of prostitution render prostitutes unable at times to meet
      basic human needs, vulnerable to violence, and at risk for sexually transmitted
      disease. Since April 1989 a mobile van from a private foundation has been
      contacting prostitutes throughout the five boroughs of New York City to provide
      HIV testing and counseling and to distribute condoms, bleach kits for cleaning
      needles, and HIV prevention information. Data collected from 1,963 female
      prostitutes are discussed in this article. Information is provided on
      demographics, family and living arrangements, sex and drug practices, HIV status
      and risk reduction practices, and health history. Methods are discussed for
      social workers to develop creative ways to provide outreach and develop
      relationships with a vulnerable population that invests much effort in remaining
      concealed.

PMID- 8560325
TI  - Rates of first hospitalizations for affective psychoses in Costa Rica.
AB  - What demographic, geographic and temporal factors characterize the rate of first
      hospitalizations for affective psychosis in Costa Rica? This report presents
      graphically the first hospitalization rates for the whole country of Costa Rica,
      with analysis of specific rates for the subgroups by age, sex, marital status,
      level of education, occupation, place of residence, and place of birth, as well
      as separate rates by month and date of hospital admission, monopolar first
      admissions increased slowly from the age of 10 to the age of 45 years, then
      "exploded" to a peak between 55 and 65 years, then declined somewhat. The
      educational group among men with the highest rate was the group with at least
      some university education. Professionals, clerical workers, unskilled laborers,
      and those with no occupation had high rates. Higher rates were also associated
      with being single, divorced, widowed, having no occupation, and living in rural,
      coffee-growing areas that were not too distant from the hospital.

PMID- 8560326
TI  - Hospital at war: treatment changes in mental patients.
AB  - The implications of the chemical war threat and the missile attacks during the
      Gulf War for a medium-sized psychiatric community are analyzed in terms of
      psychiatric care and management. Changes in medication, physical restraint, and
      ward transfer were observed for schizophrenic patients in active psychotic phase
      (n=50), in residual post-active phase (n = 37), and patients with long-term
      residual type (n = 167). The variables for the first week of the war (n = 250)
      were compared to those the same week 1 year before (n = 254). Patients in active
      phase and patients in residual phase received more supplementary treatment and
      radical changes in treatment; patients in active phase received more treatment
      reinforcement, as well as physical restraint, compared to patients in phase and
      residual type patients. Residual type patients remained unchanged on all
      variables. Residual type patients remained mostly indifferent, while many
      severely disturbed patients residing in open wards required only minor
      tranquilizers. Patients in active phase tended to behave very erratically while
      denying being affected by the war, and patients in residual phase overtly
      expressed their anxiety and remained in control.

PMID- 8560327
TI  - Caregivers of Turkish schizophrenic patients: causal attributions, burdens and
      attitudes to help from the health professionals.
AB  - The purpose of this study was to examine the causal attributions, difficulties,
      perceived and expected help behaviour of health care professionals, and hope for
      the future well-being of the caregivers of Turkish schizophrenic patients in
      order to form guidelines for forming a collaboration with the families of
      schizophrenic patients. Sixty caregivers were interviewed by using a semi
      structured interview schedule. The responses of the caregivers were categorized
      within the guidelines of the literature in this area. The caregivers attributed
      schizophrenia mainly to psychosocial causes, namely stressful events (50%),
      family conflicts (40%) and patients' characteristics (28%). The most frequently
      reported difficulties were family conflicts and disruptions of family life,
      subjective burden (48%), and financial costs due to the patient (27%). The number
      of difficulties reported by caregivers was related to the duration of the
      patient's illness. Caregivers perceived pharmacological treatment (42%), interest
      and support given to the caregiver (28%), and the hospitalization of the patient
      (20%) as helpful. THeir expectations of help were in similar areas. About half of
      the caregivers were optimistic about the future well-being of their relatives.
      Optimistic and pessimistic caregivers differed in the educational level of the
      caregiver and the duration of the patient's illness. The results suggested that
      the families of schizophrenics need support of professionals and the
      establishment of networks focusing on the caregivers and their relationships with
      their ill relatives and with health care institutions.

PMID- 8560328
TI  - Changes in suicide numbers in psychiatric hospitals: an analysis using log-linear
      time-trend models.
AB  - We examined the hypothesis that there is an increase in the number of suicides
      committed by psychiatric inpatients. Data were recorded in five psychiatric
      hospitals/departments in Baden-Wurttemberg (Germany) for the period between 1970
      and 1992. Statistical analysis was performed by means of log-linear time-trend
      models that allowed us to test several hypothesis, to compare their goodness of
      fit, and to correct for related factors (number of admissions, number of suicides
      in the general population). Results showed that the model of a general increase
      could be rejected. The separation of the yearly frequencies into two parts (1970
      1979 and 1980-1992) revealed an increase in the inpatient suicide rate during the
      years 1970-1979 and a slowly decreasing inpatient suicide rate during the years
      1980-1992, especially when taking admission numbers into account. Diagnostic
      subgroups (schizophrenia and depression) did not seem to deviate from these
      trends. The correction for the suicide numbers in the general population of Baden
      Wurttemberg, which exhibited a remarkable decrease in the 1980s, did not
      influence these results. We speculate that, after some starting difficulties, the
      effects of the more humane treatment procedures introduces in the 1970s are
      beginning to be felt.

PMID- 8560329
TI  - Premorbid abnormalities in mania, schizomania, acute schizophrenia and chronic
      schizophrenia.
AB  - The aim of this study was to examine the hypothesis that differences in outcome
      among affective and non-affective psychoses are associated with differences in
      the degree of developmental deviance. We conducted a retrospective survey of
      first contact cases treated over a 20-year period in a psychiatric hospital
      serving a catchment area in South London. All patients with non-depressive
      functional psychosis residing in the catchment area who received their first
      psychiatric treatment between 1965 and 1984 were included in the study. Cases
      were classified according to the relative chronicity of their illness into four
      non-overlapping groups: mania, schizomania, acute schizophrenia and chronic
      schizophrenia. There was a linear trend in the association between illness
      chronicity and proxy measures of development deviance, such as premorbid
      unemployment, single status and poor academic achievement. Compared to
      individuals with mania, schizophrenic patients had a 3-6 times increased risk of
      premorbid abnormality. For patients with schizomania and acute schizophrenia, the
      risk was 1.5-3 times greater than for manic subjects. We conclude that the
      prevalence of premorbid abnormalities is highest among chronic schizophrenia, but
      similar disturbances also occur, to a lesser degree, in less disabling affective
      and non-affective psychotic disorders.

PMID- 8560331
TI  - Anterior screw fixation of type II odontoid fractures. A biomechanical study.
AB  - STUDY DESIGN: This study examined the torsional and shear stiffness of Type II
      odontoid fractures that were stabilized with two 3.5-mm cannulated AO screws or a
      single 4.5-mm cannulated Herbert screw. OBJECTIVE: To determine the stability of
      a commonly used two-screw method versus a single-screw fixation method. Insertion
      of a single screw could make the procedure technically easier. SUMMARY OF
      BACKGROUND DATA: Biomechanical studies have shown the 4.5-mm Herbert screw to
      generate greater compressive forces than 3.5-mm cannulated screws, which are
      commonly used to anteriorly stabilize Type II odontoid fractures. No previous
      biomechanical studies have compared the shear or torsional stiffness of Type II
      odontoid fractures stabilized with these screws. METHODS: Twelve cadaver C2
      vertebrae were harvested and an osteotomy was performed to simulate a Type II
      fracture pattern. Six were stabilized with two 3.5-mm cannulated screws, and the
      remaining were stabilized with a single 4.5-mm cannulated Herbert screw. Each
      specimen then was tested in torsion through +/- 0.75 degrees, +/- 1.25 degrees,
      and +/- 1.75 degrees for 10 cycles each. Shear forces then were applied from an
      anterior to posterior direction to a maximum load of 44.48 N. RESULTS: The mean
      torsional stiffness for the Herbert screw was 1196 N.m/deg, which was
      significantly greater than the mean stiffness of the 3.5-mm screw fixation, which
      measured 434 N.m/deg. The mean shear stiffness for the Herbert screw fixation was
      106.9 kN/m, compared to 86.1 kN/m for the 3.5-mm cannulated screw. This was not
      statistically significant. CONCLUSIONS: The biomechanical properties of the 4.5
      mm cannulated Herbert screw suggest it may lend itself for use in fixation of
      Type II odontoid fractures. With only a single screw to insert, this technically
      demanding procedure may be less daunting.

PMID- 8560330
TI  - The epidemiology of bipolar affective disorder.
AB  - This paper reviews the current position of studies on the epidemiology of bipolar
      affective disorder. A disorder that cannot be recognized until sometime after its
      onset poses special difficulties for epidemiological study. These are discussed
      and attempts made to solve them. Community psychiatric surveys suggest a morbid
      risk of bipolar disorder of around 2-2.5%, but probably include many false
      positives. Studies of treated cases indicate a morbid risk of 0.5%, but will miss
      untreated cases. It is probably reasonable to suggest a compromise value of 1
      1.5%; bipolar disorder is thus still a rare condition. It is possible to quantify
      the unipolar-bipolar conversion rate, which is of the order of 5%, and is of
      particular interest that female sufferers have proportionately fewer manic
      episodes. Age at onset, possible cohort phenomena, comorbidity, and
      sociodemographic correlates are discussed.

PMID- 8560332
TI  - Assessment of unicortical and bicortical fixation in a quasistatic cadaveric
      model. Role of bone mineral density and screw torque.
AB  - STUDY DESIGN: The stabilizing potential of the Caspar Trapezial Osteosynthetic
      Plate was studied using unicortical and bicortical screw placement in cadaveric
      cervical spines. OBJECTIVE: To determine if Caspar plates secured with
      unicortical screws provide the same degree of stability as those anchored with
      unlocked bicortical screws. SUMMARY OF BACKGROUND DATA: Previous work has
      demonstrated that bicortical cervical vertebral screws are superior to
      unicortical screws in terms of pullout strength and decreased wobble. However,
      these two methods of plate fixation have not been directly compared in a
      clinically relevant cadaveric model. METHODS: The immediate and post-fatigue
      stabilizing potential of Caspar plates secured with unicortical or bicortical
      screws was assessed using a model of complete segmental instability. RESULTS:
      Unicortical screw placement resulted in inadequate stabilization in half of the
      cervical specimens. CONCLUSIONS: Our results suggest that, for the Caspar screw,
      bicortical fixation provides greater flexion-extension stability.

PMID- 8560333
TI  - The accuracy of Risser staging.
AB  - STUDY DESIGN: This study analyzed the accuracy of Risser sign staging on
      posteroanterior radiographs. OBJECTIVE: To correlate the Risser sign on a
      posteroanterior radiograph with that on an anteroposterior radiograph. SUMMARY OF
      BACKGROUND DATA: On the posteroanterior view of the spine, the full length of
      iliac apophysis is difficult to interpret. No report has assessed the relation of
      these findings. METHODS: The staging of the Risser sign was examined in 89 girls.
      In 52 subjects, the stage of the Risser sign was identical on both views, whereas
      in 37 (42%) the interpretations were different. RESULTS: On evaluation of the
      iliac apophysis using a skeletal specimen, the posteroanterior views produced a
      distorted image of the iliac apophysis, and the medial and lateral aspects of the
      apophysis were superimposed over the ilium. CONCLUSIONS: As a result of these
      findings and the fact that the Risser staging was developed for the
      anteroposterior radiograph, the appearance of the iliac apophysis on the
      posteroanterior radiograph cannot be used as a reliable indicator of skeletal
      maturity.

PMID- 8560334
TI  - Intraoperative lower extremity reflex muscle activity as an adjunct to
      conventional somatosensory-evoked potentials and descending neurogenic monitoring
      in idiopathic scoliosis.
AB  - STUDY DESIGN: Lower extremity polysynaptic reflexes and descending neurogenic
      motor and ascending somatosensory activity were recorded. OBJECTIVE: Two cases
      are presented to illustrate the intraoperative use of lower extremity reflex
      recordings for detecting compromise of spinal cord function. SUMMARY OF
      BACKGROUND DATA: Lower extremity reflex processing can be used to measure
      integrated spinal cord activity, whereas descending neurogenic and ascending
      somatosensory potentials measure only long tract function. METHODS: Eight
      channels of lower extremity polysynaptic reflex activity were recorded
      simultaneously after unilateral lower extremity mixed nerve stimulation.
      Sequential descending neurogenic and ascending somatosensory activity was
      recorded simultaneously with reflex recordings. RESULTS: In these two patients
      with idiopathic scoliosis, intraoperative reflexes changed before descending
      neurogenic and before ascending somatosensory activity changed. High-amplitude
      synchronous persistent reflex activity correlated with a postoperative neurologic
      deficit. Low-amplitude asynchronous transient reflex activity was not associated
      with a postoperative neurologic deficit. CONCLUSION: Intraoperative lower
      extremity reflex changes are more sensitive to spinal cord compromise than are
      changes in long tract function. Lower extremity polysynaptic reflexes monitor the
      integrated activity of the spinal cord that is responsible for the control of
      complex motor behavior.

PMID- 8560335
TI  - The prevalence and clinical features of internal disc disruption in patients with
      chronic low back pain.
AB  - STUDY DESIGN: This was a cross-sectional analytic study of patients with chronic
      low back pain. OBJECTIVE: To investigate whether the criteria for internal disc
      disruption, as adopted by the International Association for the Study of Pain,
      could be satisfied in patients with chronic low back pain and to test whether
      there were any conventional clinical features that could identify this condition.
      SUMMARY OF BACKGROUND DATA: Internal disc disruption has been postulated as an
      important cause of low back pain. To diagnose this condition, the International
      Association for the Study of Pain taxonomy requires that pain be reproduced on
      provocation discography and that computed tomography discography reveal internal
      disc disruption, provided that as a control, stimulation of at least one other
      disc fails to reproduce pain. METHODS: Ninety-two consecutive patients with
      chronic low back pain and no history of previous lumbar surgery were studied.
      Each patient underwent a standard physical examination. Computed tomography
      discography was performed at a minimum of two levels. RESULTS: The diagnostic
      criteria for internal disc disruption were fully satisfied in 39% of patients,
      most commonly at L5-S1 and L4-L5. None of the clinical tests used could
      differentiate between those patients with internal disc disruption and other
      patients. CONCLUSIONS: A diagnosis of internal disc disruption can be made in a
      significant proportion of patients with chronic low back pain, but no
      conventional clinical test can discriminate patients with internal disc
      disruption from patients with other conditions.

PMID- 8560336
TI  - The prevalence of cervicogenic headache in a random population sample of 20-59
      year olds.
AB  - STUDY DESIGN: From a random population sample, those experiencing frequent
      headaches were identified. They were examined to determine how many fulfilled the
      1990 International Headache Society classification criteria for cervicogenic
      headache. OBJECTIVE: To estimate the prevalence of cervicogenic headache in the
      general population and in the group experiencing frequent headaches. SUMMARY OF
      BACKGROUND DATA: Only with the publication of the 1990 headache classification
      criteria did a generally accepted clinical definition of cervicogenic headache
      emerge. The prevalence of this form of headache has been estimated only in two
      highly selected in-clinic patient populations. No data exist regarding the
      prevalence in representative unselected populations. METHODS: A short
      questionnaire on headaches was mailed to 826 randomly selected residents of a
      midsized Danish town. A group of 57 individuals in the age range 20-59 years who
      reported having headache episodes on 5 or more days in the previous month were
      identified. Forty-five of the 57 were eventually interviewed and examined with
      respect to the IHS criteria for cervicogenic headache (the radiological criteria
      were omitted on ethical grounds). RESULTS: Of the 45 persons examined, eight
      fulfilled the diagnostic criteria for cervicogenic headache, equivalent to a
      prevalence in the headache group of 17.8% (95% confidence interval = 8%-32%).
      CONCLUSIONS: Cervicogenic headache appears to be a relatively common form of
      headache, similar to migraine in prevalence.

PMID- 8560337
TI  - Estimating the prevalence of low back pain in the general population. Evidence
      from the South Manchester Back Pain Survey.
AB  - STUDY DESIGN: This report gives the results of a population-based cross-sectional
      mailed questionnaire, with prospective follow-up of survey responders and
      nonresponders. OBJECTIVE: To determine the 1-month period prevalence of low back
      pain in an adult population in the United Kingdom and to estimate the effect of
      nonresponse bias. SUMMARY OF BACKGROUND DATA: Previous United Kingdom population
      studies have reported a 1-year period prevalence of low back pain of 37%.
      However, the definitions of low back pain have varied, and the influence of
      nonresponse rarely has been reported. METHODS: The study population was made up
      of all 7669 adults (18 to 75 years old) registered with two family practices in a
      sociodemographically mixed suburban area. The questionnaire, including a pain
      drawing to identify the site of any pain, was mailed to the entire study
      population. Two repeat mailings were sent to nonresponders. Family practice
      consultations about low back pain by individuals from the study population were
      monitored over the following 12 months using computerized records of all surgery
      contacts. RESULTS: Of the study population, 4501 (59%) responded. The 1-month
      period prevalence of low back pain was 39% (35% in males, 42% in females). The
      age distribution was unimodal, with peak prevalence in those aged 45 to 59 years
      old. Responders to the first mailing had a small but nonsignificant increase in
      prevalence compared with those who responded to the second or third mailing.
      Nonresponders had a subsequent consultation rate for low back pain that was 22%
      lower than that for the survey responders. CONCLUSIONS: After considering
      potential differences in nonresponders, the estimated 1-month prevalence of low
      back pain was between 35% and 37%. Prevalence figures in survey responders may
      overestimate the true population prevalence by a modest amount.

PMID- 8560338
TI  - The influence of initial horizontal weight placement on the loads at the lumbar
      spine while lifting.
AB  - STUDY DESIGN: This was a biomechanical study of the effect of the initial
      horizontal distance between a person lifting and the load. Experimental data were
      analyzed using a dynamic rigid link model. OBJECTIVE: To determine the effect of
      the initial horizontal load placement on the moments acting on the lumbar spine
      and the lower extremity joints during lifting, and to determine the role of the
      lower extremities during lifting from the floor. SUMMARY OF BACKGROUND DATA:
      Epidemiologic studies have implicated lifting as a cause of back pain, and over
      80% of all worker's compensation back injuries are considered to be caused by
      manual material handling Guidelines have been proposed to increase the safety of
      lifting, but they are primarily based on static biomechanical analyses,
      psychophysical data, and physiologic limitations. METHODS: Each of 12 male
      subjects lifted a weight box containing 0 to 300 N, in 100-N increments. Each
      subject performed 20 lifts--four weights at five horizontal distances (20, 30,
      40, 50 and 60 cm). Motion was measured with an optoelectronic system, ground
      reaction forces were measured with a force plate, and moments were calculated
      using a rigid link model. RESULTS: The peak predicted L5-S1 moment increased as
      the weight and horizontal distance increased. The influence of horizontal
      distance on moment magnitude was nonlinear. As the distance changed from 20 to 40
      cm, the distance-related rate of increase was approximately one-half of that
      occurring with a distance change from 40 to 60 cm. This can be explained by the
      need to reach out further, beyond 40 cm, which is accomplished by a deeper
      flexion of the knees and ankles and an anterior translation of the upper body and
      arms. CONCLUSION: As the horizontal distance at the start of a lift increased,
      the peak moment acting on the lumbar spine also increased, but the increase was
      nonlinear. This is explained by a change in the technique of lifting when the
      distance is 40 cm or greater.

PMID- 8560339
TI  - Assessing health-related quality of life in patients with sciatica.
AB  - STUDY DESIGN: This study analyzed health-related quality-of-life measures and
      other clinical and questionnaire data obtained from the Maine Lumbar Spine Study,
      a prospective cohort study of persons with low back problems. OBJECTIVE: For
      persons with sciatica, back pain-specific and general measures of health-related
      quality-of-life were compared with regard to internal consistency, construct
      validity, reproducibility, and responsiveness in detecting small changes over a 3
      month period. SUMMARY OF BACKGROUND DATA: Data were collected from 427
      participants with sciatica. Baseline in-person interviews were conducted with
      surgical and medical patients before treatment and by mail at 3 months. METHODS:
      Health-related quality-of-life measures included symptoms (frequency and
      bothersomeness of pain and sciatica) functional status and well-being (modified
      back pain-specific Roland scale and Medical Outcomes Study 36-item Short Form
      Health Survey (SF-36), and disability (bed rest, work loss, and restricted
      activity days). RESULTS: Internal consistency of measures was high.
      Reproducibility was moderate, as expected after a 3-month interval. The SF-36
      bodily pain item and the modified Roland measure demonstrated the greatest amount
      of change and were the most highly associated with self-rated improvement. The
      specific and generic measures changed in the expected direction, except for
      general health perceptions, which declined slightly. A high correlation between
      clinical findings or symptoms and the modified Roland measure, SF-36, and
      disability days indicated a high degree of construct validity. CONCLUSIONS: These
      measures performed well in measuring the health-related quality-of-life of
      patients with sciatica. The modified Roland and the physical dimension of the SF
      36 were the measures most responsive to change over time, suggesting their use in
      prospective evaluation. Disability day measures, although valuable for assessing
      the societal impact of dysfunction, were less responsive to changes over this
      short-term follow-up of 3 months.

PMID- 8560340
TI  - Posterior instrumentation and anterior interbody fusion for tuberculous kyphosis
      of dorsal and lumbar spines.
AB  - STUDY DESIGN: Thirty-nine adults and five children with active spinal
      tuberculosis and resulting kyphosis of the dorsal and lumbar spine who had
      combined posterior instrumentation and anterior interbody fusion were observed to
      determine whether the corrected spinal deformity could be maintained until solid
      fusion. OBJECTIVE: To evaluate the effectiveness of the combined two-stage
      procedure for treating kyphosis due to active spinal tuberculosis. SUMMARY OF
      BACKGROUND DATA: Until 1970, with all methods of treatment, kyphosis due to
      active spinal tuberculosis tended to increase during therapy. Most of the
      patients treated with these methods were not happy with this residual kyphosis,
      even though their disease was arrested or cured. Kyphosis became their main
      concern regarding further treatment. METHODS: A combined two-stage procedure,
      under the cover of 18 months of triple chemotherapy, was used for all patients.
      For posterior stabilization, the Harrington distraction system, Rush nails or
      Steinmann pins and wires, and Texas Scottish Rite Hospital instrumentation were
      used. The diagnosis of successful interbody fusion was made if there was no loss
      of correction, no graft resorption or graft bed resorption, and if there was
      visible graft remodeling, such as trabeculation between the graft beds and graft
      and the graft hypertrophy. RESULTS: In the 39 adults, average preoperative,
      immediate postoperative, and last follow-up kyphosis angles were 37 degrees, 16
      degrees, and 18 degrees, respectively. In four children, the average
      preoperative, immediate postoperative, and last follow-up kyphosis angles were 55
      degrees, 28 degrees, and 31 degrees, respectively. The loss of correction did not
      exceed 3 degrees. For one-segment spondylodesis, the average fusion times were 4
      months in adults and 3.5 months in children. For a two-segment fusion, the
      average fusion times were 6 months in adults and 6.3 months in children.
      CONCLUSION: Posterior instrumental stabilization and anterior interbody fusion
      were found helpful in arresting the disease early, providing early fusion,
      preventing progression of kyphosis, and correcting the kyphosis.

PMID- 8560341
TI  - Transpedicular fixation for the treatment of isthmic spondylolisthesis in adults.
AB  - STUDY DESIGN: This study analyzed the fusion rate and clinical success rate in
      adult patients undergoing surgical treatment for symptomatic, low grade, isthmic
      spondylolisthesis. A postoperative questionnaire and grading scale were used to
      judge clinical success. Successful fusion was judged using radiographic criteria.
      OBJECTIVE: To evaluate the clinical success and fusion success in a group of
      adult patients undergoing instrumented posterolateral arthrodesis for symptomatic
      isthmic spondylolisthesis. SUMMARY OF BACKGROUND DATA: Seventeen consecutive
      adult patients with symptomatic low grade isthmic spondylolisthesis underwent the
      identical surgical procedure consisting of Gill laminectomy, L5 nerve root
      decompression, Luque pedicle-screw plate instrumentation, and posterolateral
      arthrodesis at L5-S1 using autogenous iliac crest bone graft. Results were
      analyzed at an average 30-month follow-up. METHODS: An independent observer
      reviewed the results using a postoperative questionnaire to determine rates of
      return to work, symptom relief, and analgesic medication usage. Radiographs were
      evaluated to determine the fusion status. RESULTS: Seventeen patients were
      evaluated at an average of 30 months after the index procedure. Sixteen of 17 had
      solid fusions using radiographic criteria. Sixteen of 17 had satisfactory
      clinical results. Eight of 13 (62%) employed patients, including three of six
      patients with worker's compensation, returned to their usual jobs. CONCLUSIONS:
      An instrumented posterolateral arthrodesis in combination with a Gill procedure
      and L5 nerve root decompression results in a high rate of fusion, satisfactory
      clinical success, and a high rate of return to work.

PMID- 8560342
TI  - Intraoperative chemonucleolysis as an adjunct to lumbar discectomy.
AB  - STUDY DESIGN: This is a report of a series of 104 patients who underwent lumbar
      discectomy and chemonucleolysis at the University of Virginia between 1985 and
      1989. OBJECTIVE: The primary objective was to determine the safety of this
      procedure. A secondary objective was to begin studying its efficacy. SUMMARY OF
      BACKGROUND DATA: This is the first report on the use of chymopapain during open
      surgery. METHODS: Patients with low back pain and radicular symptoms not cured
      with conservative therapy were selected for participation in the study.
      Intraoperatively, disc spaces were injected with 2 ml of chymopapain. Patients
      were followed-up for an average of 5 years. Patients were surveyed regarding pain
      relief, and failures of the procedure were analyzed. RESULTS: Seventy percent of
      patients reported good or excellent pain relief. Operative failures,
      characterized by reoperation at the same level, totaled 9.6%. Recurrent disc
      herniation at the time of reoperation occurred in 4.8%. CONCLUSION: The procedure
      is safe and the relief of pain was similar to that in other published series. The
      suggestion is that the rate of recurrent disc herniation is reduced.

PMID- 8560343
TI  - Traumatic atlantoaxial rotatory subluxation and dislocation.
AB  - STUDY DESIGN: This is a retrospective single-patient case report with a
      literature review. OBJECTIVE: To report on a neurologically intact adult with
      bilateral traumatic atlantoaxial rotatory subluxation/dislocation and associated
      facet fracture, and present a review of the literature. SUMMARY OF BACKGROUND
      DATA: Unilateral rotatory dislocation is relatively common at the atlantoaxial
      articulation. On the contrary, atlantoaxial rotatory subluxation with bilateral
      facet dislocation is uncommon, particularly in adults. Periodic reports have
      appeared in the literature regarding this entity in children, but only two
      previous citations have involved adults. METHODS: The patient was followed-up
      through personal examination and chart review from initial presentation to 5
      months after discharge. RESULTS: Closed reduction with cervical traction was
      followed by surgical fusion with stable repair and no neurologic deficits over 5
      months follow-up. CONCLUSIONS: Traumatic bilateral atlantoaxial rotatory
      subluxation is uncommon in adults. This probably is due to the unique
      biomechanical features of the atlantoaxial articulation and the probable
      lethality of injury to the adjacent medulla or vertebral arteries before
      presentation at the trauma center.

PMID- 8560344
TI  - Is there a link between acute spinal epidural hematoma and aspirin?
AB  - STUDY DESIGN: This is a report of a patient with acute spinal epidural hematoma
      taking aspirin, 250 mg/day. OBJECTIVE: To describe the association of spinal
      epidural hematoma and aspirin. SUMMARY OF BACKGROUND DATA: In about 50% of
      patients, the cause of acute spinal epidural hematoma is obscure. Analysis of
      possible mechanisms is necessary. METHODS: Diagnostic lumbar puncture,
      suboccipital myelography, and surgical removal of the hematoma was performed.
      RESULTS: Increased bleeding was noticed during these procedures. Bleeding time
      was normal 6 days after discontinuance of aspirin. CONCLUSION: Because aspirin is
      widely used, its role in causing spinal epidural hematoma will remain
      conjectural. For the present patient, however, it was postulated that aspirin had
      a major impact on the extent of the epidural bleeding. There should be awareness
      of a possible link between aspirin and spinal epidural hematoma.

PMID- 8560345
TI  - Primary xanthoma of thoracic spine presenting with myelopathy.
AB  - STUDY DESIGN: This retrospective case study reports on a patient with an isolated
      primary xanthoma arising in the second thoracic vertebra with paravertebral and
      spinal canal extension. OBJECTIVE: The possibility of this lesion's occurrence in
      the spine is presented with radiologic and pathologic findings appropriate for
      the diagnosis of spinal xanthoma. SUMMARY OF BACKGROUND DATA: Primary xanthoma of
      bone is an extremely rare but benign entity. It has not been previously described
      in this location, and has been described only once in the spine at all. METHODS:
      The mass was resected by curettage, and posterior instrumentation was
      successfully performed. Preoperative radiographs and magnetic resonance imaging
      of the thoracic spine were performed, as was histologic examination of the
      lesion. RESULTS: Radiographs of the upper thoracic spine revealed a lytic defect.
      Magnetic resonance imaging revealed a heterogeneous lesion that was enhanced upon
      the administration of gadolinium-diethylenetriaminetetraacetic acid. Histologic
      examination revealed a cellular lesion consisting of lipid-laden macrophages,
      fibroblasts, and scattered Touton giant cells. These features correspond to
      descriptions of primary xanthoma of bone. Two years after surgery, the patient
      was neurologically intact with no evidence the lesion would recur. CONCLUSIONS:
      Primary xanthoma of bone is considered a benign lesion and can be successfully
      treated by local resection without adjuvant therapy. It should be considered part
      of the differential diagnosis of a mass lesion, with appropriate signal
      characteristics presenting in a thoracic vertebra.

PMID- 8560346
TI  - Progressive kyphosis and neurologic compromise complicating spondylothoracic
      dysplasia in infancy (Jarcho-Levin syndrome).
AB  - STUDY DESIGN: This is a case report and review of the literature. OBJECTIVE: To
      review the orthopedic literature regarding the spinal abnormalities found with
      spondylothoracic dysplasia, and to present the history and management of severe
      kyphosis with neurologic impairment in an infant with spondylothoracic dysplasia.
      SUMMARY OF BACKGROUND DATA: Spondylothoracic dysplasia (Jarcho-Levin syndrome) is
      a rare form of short-limbed dwarfism characterized by extensive vertebral and
      chest-wall abnormalities. Although the spinal anomalies generally are
      radiographically severe, no patient previously reported in the English orthopedic
      literature has required surgical stabilization. METHODS: The clinical findings,
      course, and surgical management of an infant with spondylothoracic dysplasia and
      severe congenital kyphosis are presented. This patient required anterior
      decompression and anterior/posterior spinal fusion to obtain stabilization. The
      follow-up from the index surgical procedure was 2 years. RESULTS: The patient
      underwent an initial anteroposterior fusion and decompression at 5 months of age.
      She underwent revision of both anteroposterior procedures 7 months later because
      of pseudarthroses and a progressive kyphosis. Her residual neurologic abnormality
      was minimal and she appeared to have a stable fusion at 24 months post-index
      procedure. CONCLUSIONS: The spinal abnormalities associated with spondylothoracic
      dysplasia may not be as benign as previously reported. Sagittal, as well as
      frontal, plane deformities may exist secondary to multiple hemivertebrae. Longer
      life span, possibly due to improved pulmonary care, may increase the incidence of
      deformities requiring intervention.

PMID- 8560347
TI  - Functional disability scales for back pain.
AB  - Functional disability scales for back pain are reviewed for content and
      measurement properties, concentrating on five widely used questionnaires. Current
      methodological issues in functional assessment also are discussed.

PMID- 8560348
TI  - Spondylolysis. An historical review.
AB  - This historical review covers the earliest recorded findings and descriptions of
      lumbar spondylolysis, as well as the century-old etiologic controversy regarding
      this condition. The importance of the work of Robert zu Coblenz in 1855 is
      recognized regarding the biomechanical and clinical understanding of the nature
      of spondylolysis. Other important medical personalities are discussed through an
      extensive look at the literature.

PMID- 8560349
TI  - Degenerative lumbar spondylolisthesis: a meta-analysis of literature 1970-1993.

PMID- 8560350
TI  - [Ureteral obstruction in the kidney transplant patient].
AB  - Ureteric obstruction is a common complication following kidney transplantation
      ranging from 2% to 5% after one year and till 9% after five years post
      transplantation. It hinders the return to good renal function and in certain
      cases leads to the organ loss or patient mortality. Technical factors and
      ureteric ischemia are the most important causes. The authors report their
      experience with kidney transplantation and 6 cases of ureter obstruction with a
      global incidence of 5.5%. We discuss the aetiology, the management and the
      treatment for this complication emphasizing the importance of either color
      Doppler ultrasound for the diagnosis or percutaneous nephrostomy for the
      radiological establishment of the blocked level as well as the first choice of
      treatment. In order to reduce the morbidity and mortality for this complication
      early and aggressive treatment is advocated.

PMID- 8560351
TI  - [Effects of cyclosporin A on various indices of cholestasis in kidney transplant
      recipients].
AB  - A cholestatic syndrome has been reported as one of the main side effects of CyA
      therapy. The aim of the present study was to evaluate frequency and degree of
      severity of the cholestatic syndrome in a group of patients with renal transplant
      treated with CyA. In 55 patients we evaluated both clinical: jaundice, pruritus,
      presence of biliary lithiasis and biochemical parameters: total serum biliary
      salts (TBS), total bilirubin (TB), alkaline phosphatase (AP), gammaglutamyl
      transpeptidase (GGT), transaminase (AST, ALT), cholesterol (CT), triglycerides
      (TG), HDL-cholesterol (HDL-C) and compared them with a control group matched for
      sex and age. In the transplant patients significantly higher values of TBS, TB,
      AP (p < 0.05) were found; 55% of the patients had above mean values of at least
      one of the classical parameters of liver function and an higher frequency of
      biliary lithiasis was also found, in the absence of the classical risk factors.
      However, none of the patients presented severe signs of hepatic disease and to
      date it has never been necessary to stop treatment. In conclusion, our study
      shows that the dosage of CyA used at present is quite safe; however, it is
      necessary to monitor in these patients some parameters of liver function to
      prevent the minor side effects we observed from progressing into more serious
      damage.

PMID- 8560352
TI  - [Multiple primary neoplasia in a urologic setting. Clinical review and tentative
      etiopathogenetic profile].
AB  - The authors present the results of a retrospective study aimed at identifying the
      most common neoplastic associations diagnosed in urology. Between 1991-94 430
      patients with neoplasia of the urogenital tract were diagnosed and studied: 50
      (11.6%) showed a second primary neoplasia (48 cases dual, 2 cases triple). The
      long-term results show that the most frequent neoplastic associations were, in
      order of greatest incidence, those involving the gastrointestinal, respiratory
      and hemolymphatic regions. In 30 patients the second neoplasia became manifest
      within 5 years of the first, whereas neoplasias of the uterus and adnexa or
      breast have a late onset. An oncological familial pattern was observed in 14
      cases, but it was not easy to analyse the clinical significance. The genetic
      interpretation of each individual neoplastic association is still complex and
      difficult to evaluate. Biomolecular research may in the future be able to provide
      some of the vital data for a correct etiopathogenetic classification.

PMID- 8560353
TI  - [Tumor enucleation as the conservative treatment of choice for renal carcinoma].
AB  - Nine cases of renal cell carcinoma treated by conservative elective surgery
      (enucleation) are reported. The positive results obtained, together with the
      experience of others, indicate enucleation as an effective treatment in selected
      patients with small, peripheral and low-stage tumors.

PMID- 8560354
TI  - [Surgical treatment of benign prostatic hypertrophy and Kelami syndrome].
AB  - The authors analyze a group of 116 consecutive patients treated with transvesical
      prostatic adenomectomy or transurethral prostatic resection for benign prostatic
      hypertrophy (BPH) isolated five of them with a Kelami syndrome. These patients,
      aged between 53 and 70 years old, had a relevant ventral penile deflection with
      severe sexual impairment postoperatively. Among them only one asked for a
      corrective surgical procedure. Aetiology, preventive measures and therapeutic
      choices are discussed. Authors pointed out that this syndrome is actually
      underestimated considering the high number of transurethral or open surgery
      procedures for BPH.

PMID- 8560355
TI  - [Gynecomastia in chronic renal insufficiency. Presentation of a clinical case].
AB  - Gynecomastia may occur in men with chronic renal failure, developing in the
      course of complex endocrine abnormalities. It is often associated with aberration
      in the hypothalamo-pituitary-testicular axis even producing a severe
      hypogonadism. A case of monolateral gynecomastia in a hemodialyzed young man,
      without other clinical and endocrine signs, is described.

PMID- 8560356
TI  - [Unusual presentation of bilateral ureterocele in an adult Black male. Clinical
      case].
AB  - Ureterocele is a congenital urinary abnormality characterized by the presence of
      an intra-bladder hernia or cystic ballooning of the lower end of a ureter between
      the mucosa and muscle of the bladder. The abnormality leads to urinary retention
      and recurrent urinary tract infection which can cause irreversible damage to the
      kidney. Antenatal ultrasound diagnosis of ureterocele is possible but remains
      difficult. The disease is confirmed during radiologic examination after birth,
      and renal function is assessed by 99mTc-DMSA. Ureterocele, while not an uncommon
      pediatric urologic problem, has been reported only rarely in adults. It is
      bilateral in 10% of cases, is rare in black people, and requires thoughtful
      management decisions. A relatively uncommon case of bilateral ureterocele with
      single ureter, associated with left vesicoureteral reflux, in African black man
      is reported. The patient was investigated by ultrasonography and intravenous
      urography. Surgical transvesical right "osteoplasty" and excision of the left
      ureterocele plus ureteric reimplantation, using Politano-Leadbetter technique,
      were performed. The surgical approach to ureterocele is discussed and we
      underlined the difficulty of therapeutic decisions, especially if surgery is
      considered.

PMID- 8560357
TI  - Intrauterine unilateral torsion of the spermatic cord.
AB  - A case of unilateral torsion of the spermatic cord in a newborn is reported.
      Extra-vaginal neonatal torsion of the spermatic cord, although rare, is being
      recognized with increasing frequency. Treatment requires immediate surgical
      exploration. Controversy exists concerning the urgency of exploration as well as
      the need for contralateral orchiopexy, since some reports suggest that the
      contralateral testicle is not a risk for torsion. Treatment of the ipsilateral
      testicle is determined by operative findings.

PMID- 8560358
TI  - [The Urovac bladder evacuator: comparison with traditionally used devices].
AB  - Bladder evacuation device "Urovac": comparison with the conventional most used
      devices. We evaluated a new technique for bladder evacuation primarily during
      Turp using a disposable device called Urovac. This device proved to be better for
      evacuation of prostatic chips than both the Ellik evacuation and Toomey syringe.

PMID- 8560359
TI  - [Treatment of urinary tract infections with macro-crystalline nitrofurantoin].
AB  - Therapy of urinary tract infections with nitrofurantoin macro-crystals. The aim
      of this study is to evaluate the therapeutic effectiveness of two dosages of
      nitrofurantoin macro-crystals. Between January 1993 and February 1994, 101
      patients (54 male and 47 female), either suffering from urinary tract infections
      or on whom internal examination had been carried out, were treated with
      nitrofurantoin macro-crystals. There were divided into two groups: A, a posology
      of 100 mg 3 times daily for 7 days and B, a posology of 100 mg 4 times daily for
      7 days. A urine culture was carried out on all patients before and after
      treatment. E. Coli was found in 60.5% of cases, Streptococcus Faecalis in 12.7%
      and Staphylococcus aureus in 5.6%. Infection was eliminated in 85.3% of patients
      in group A and 93.9% in group B. The dysuric symptomatology was cured in 84.6% of
      patients in group A, and 89% in group B. The statistic elaboration of the results
      with X2 and p tests did not reveal any difference between the two groups
      examined.

PMID- 8560360
TI  - Social work and the new integrative hospital.
AB  - The principles of bureaucratically organized hospitals are counter to the values
      of social work. In a move to new integrative hospitals, social work can be the
      champions. The values of the social work profession that emphasize negotiation,
      change, flexibility, relationships, choice and control, the right to exercise
      autonomy, and participatory decision-making, are congruent with the principles
      that form the foundation for the new integrative models for hospitals. A model
      for the organization of social work practice, continuing education, standard
      setting, research and the student program. The Professional Standards Group, is
      proposed for the new hospital age.

PMID- 8560361
TI  - Occupational stress among AIDS social service providers.
AB  - This survey reveals high levels of job-related stress among social workers,
      counselors and health educators working with HIV/AIDS patients in five large,
      urban medical centers. Stress is associated not only with the severity of AIDS as
      a disease, but also with several organizational characteristics of respondents'
      job sites. The availability and usefulness of several on-site, stress-reduction
      strategies are explored. Overall, where services such as stress-reduction
      workshops, support groups, and rotations away from direct patient care are
      offered, workers participate in them and perceive them as useful in reducing job
      related stress. Interest in these and other stress-reduction services is high
      among those who do not currently have them available.

PMID- 8560362
TI  - Tuberculosis and AIDS: the impact on the hospital social worker.
AB  - The second decade of the AIDS epidemic is marked by increasing numbers of people
      being diagnosed with HIV infection as well as mycobacterium infection (pulmonary
      tuberculosis). The convergence of these two epidemics presents new challenges for
      social workers. Serious threat of HIV infection from occupational exposure was
      diminished by the knowledge of roots of disease transmission. TB, on the other
      hand, is an airborne infectious disease. Social workers working with patients
      over long periods of time in confined spaces can be at risk for contracting TB.
      Hospital social workers must struggle and advocate for full information regarding
      the incidence of risk and risk precaution. They must find ways of coping with
      their own emotional responses to the resurgence of TB and their own fear of
      exposure to avoid physical and emotional withdrawal from their HIV infected
      patients. This paper will address the unique impact on the worker's personal
      safety, the impact on the therapeutic relationship with the patient, and provide
      action steps for workers facing these challenges.

PMID- 8560363
TI  - Psychosocial outcomes of HIV illness in male and female African American clients.
AB  - With the rapid growth of HIV infection among African Americans, the issue of how
      medical problems relate to psychological functioning in the black community
      population has acquired new meaning and urgency for health care policy. To
      develop effective strategies to meet the mental health needs of infected African
      Americans we need a better understanding of the pattern of Association between
      HIV and psychological distress. The objective of this study is to test several
      hypotheses that predict depression and anxiety in black adults infected with HIV.
      Our conceptual model is derived from learned helplessness theory (Seligman,
      1975), the concept of perceived coherence (Antonovsky, 1980; Lewis & Gallison,
      1989), and social support theory (Cohen & Willis, 1985). Instruments used in the
      study include: The Center for Epidemiological Studies-Depression (CES-D) Scale
      (Radloff, 1977), the Anxiety Scale (Lewis, Firsich, and Parsell, 1979), and the
      Perceived Coherence Scale (Lewis, 1989). Data were obtained from 255 HIV infected
      black males and females (age > or = 18) who sought support, counseling, and
      maintenance services from one of three HIV care and referral centers in the Mid
      South. The results of the study emphasize the relative importance of perceived
      physical symptoms over stage of illness for psychological functioning among
      African American adults with HIV. Further, the findings also demonstrate the
      potential importance of perceived coherence for psychological functioning. Black
      clients who reported higher perceived coherence, regardless of the stage of
      illness or level of HIV symptoms, had lower anxiety and depression. Significant
      gender differences in depression are also observed and implications are drawn for
      strategies to address HIV related mental health care needs of African Americans.

PMID- 8560364
TI  - Occupational exposure of health care workers (HCWs) to human immunodeficiency
      virus (HIV): stress reactions and counseling interventions.
AB  - As more people become infected with HIV, Health Care Workers (HCWs) have a
      greater likelihood of being exposed at work. HIV exposure threatens the life of
      the HCW and can elicit a stress reaction. Although HCWs have reactions similar to
      those of people who have been exposed to other traumatic events, the nature of
      this stressor and the length of time it lasts is unique. This article presents
      counseling interventions that address the needs of the individual HCW during this
      event. These counseling guidelines promote the HCW's discussion of the event and
      any relevant past unresolved traumatic experiences; evaluate and aid the worker
      and his or her support system; provide information on stress reactions and HIV;
      examine the HCW's practice methods; and helps to reintegrate the HCW back into
      the work environment.

PMID- 8560365
TI  - Racial minorities and other high-risk groups with HIV and AIDS at increased risk
      for psychological adjustment problems in association with health locus of control
      orientation.
AB  - This study compared minority subjects (n = 45) with non-minority subjects (n =
      49) with HIV and AIDS, examining levels of perceived locus of control over health
      status, and whether different health locus of control (HLOC) orientations
      (internal, powerful others, or chance) determined psychological adjustment as
      measured by depression levels, and intrusive and avoidant thoughts. Gender,
      lifestyle orientation, and socioeconomic status were also included as predictor
      variables. It was determined that minority subjects were significantly more
      likely to believe that their health status was in the hands of powerful others or
      chance. Further, an external HLOC orientation, in most instances, was associated
      with problems in psychological adjustment for subjects overall, and particularly
      for females and those of lower socioeconomic status. Additional findings and
      implications for social work are discussed.

PMID- 8560366
TI  - Social work with dying and bereaved clients: helping the workers.
AB  - This paper considers the stresses and satisfactions experienced by health care
      social workers as they help clients with grief and loss at a time of great fiscal
      restraint. Their clients face life-threatening illnesses such as AIDS and many
      forms of cancer. There are untimely losses in families and communities whose
      resources are dwindling. As social workers confront struggles with death and
      bereavement, they may receive limited support to deal with these stresses in
      their work. The authors suggest administrative strategies both to help workers
      reduce stress and increase satisfactions and to demonstrate the value of social
      work services to dying and bereaved clients along a continuum of health care.

PMID- 8560367
TI  - Educating African-Americans about cancer prevention and detection: a review of
      the literature.
AB  - The high incidence of cancer mortality and morbidity among African-Americans has
      led to a need for cancer education and detection programs designed for this
      underserved population. This review of the literature focuses on key cancer
      related health beliefs, barriers to utilization, and methods of intervention that
      should be considered in developing programs for African-Americans. Implications
      for social work practice are discussed.

PMID- 8560368
TI  - Folk medicine use: diverse populations in a metropolitan area.
AB  - This paper discusses folk medicine practices among four groups--African
      Americans, Mexican-Americans, Chinese-Americans and White non-Hispanics--in an
      urban area. Folk medicine or home remedies are defined as "cures" that have been
      passed on through generations and are part of the tradition of the group. The
      data show that folk medicine and home remedies are widely used among all groups
      even though these practices are often viewed as primarily limited to rural
      settings. Folk medicine remedies are utilized in addition to, rather than in
      place of, formal biomedical health care. Folk medical cures are not used for
      chronic illness but primarily to treat minor illnesses and to prevent serious
      illness. Implications are drawn for social work practitioners in health care
      settings.

PMID- 8560370
TI  - Supportive and unsupportive interactions as perceived by cancer patients.
AB  - This exploratory qualitative study was undertaken to expand our knowledge of
      cancer patients' perceptions of supportive and unsupportive interactions with
      members of their social networks and the factors that lead them to evaluate
      certain kinds of support as helpful and others as unhelpful. Fifteen cancer
      patients were interviewed using a structured interview schedule. The interview
      focused on several aspects of the social support process, including types of
      helpful and unhelpful behaviours, perceived contingencies affecting the
      expression of supportive and unsupportive behaviours and appraisals of helpful
      and unhelpful interactions.

PMID- 8560369
TI  - Cancer screening utilization: is there a role for social work in cancer
      prevention?
AB  - Colorectal cancer is a life threatening, yet treatable, disease. Although early
      detection can improve health outcomes and preserve quality of life, many people
      are not screened. A post-test experimental design was used to test an
      intervention to increase screening behavior among eighty-one family practice
      patients, aged 50-70. Subjects were given a brief talk and a packet of
      educational materials. The physician recommended that each person complete a
      screening test at home. The experimental group was given a free screening test.
      The utilization rate in the experimental group was 51% compared to 0% in the
      control group. Findings suggest free kits encourage more use; yet further
      exploration is needed to explain non-use, even when free kits are provided.
      Recommendations for future social work practice and research are discussed.

PMID- 8560371
TI  - Annual statistical supplement, 1995.

PMID- 8560372
TI  - Professionalism, responsibility, and service in academic medicine.
AB  - BACKGROUND: Academic medical centers have responded to health care reform
      initiatives by launching a series of strategic plans designed to maintain patient
      flow and reduce hospital expenditures. Thought is also being given to processes
      by which the faculty can individually and collectively adjust to these changes
      and maintain morale at a time when reductions in the labor force and pay cuts are
      virtually certain. Physicians are concerned because managed care threatens their
      autonomy and jeopardizes the traditional ways in which they have carried out
      their multiple missions. Some doctors believe that it will become increasingly
      difficult to obtain genuine satisfaction from their job. METHODS: The strategies
      that academic medical centers have begun to use to address the numerous
      challenges posed by a system of health care based on managed competition are
      reviewed. Potential mechanisms by which academic departments can continue to find
      fulfillment in an environment that threatens their traditional missions and
      values are discussed. RESULTS: A study of the social and historical origins of
      medicine in the United States reveals that the introduction of corporate medicine
      in the United States was destined to happen. Strategies implemented by academic
      medical centers in response to managed care include building an integrated
      delivery network, the acquisition of primary care practices, increasing cost
      effectiveness, and creating physician-hospital organizations. Emphasis must be
      placed on integrating traditional core values (excellence, leadership, and
      innovation) with newer values such as patient focus, accountability, and
      diversity. A shift from rugged individualism to entrepreneurial teamwork is
      crucial. These reforms, although frightening at the onset, can serve to reaffirm
      our commitment to academic medicine and preserve our mission. CONCLUSIONS: The
      evolving managed care environment offers unique opportunities for academic
      medical centers to shape and positively impact health care delivery in the twenty
      first century. In a reconfigured model that combines core values with newer
      values, university-based physicians can continue to reap the intangible rewards
      derived from patient care, research, and education.

PMID- 8560374
TI  - Bladder stone as a rare complication one year after laparoscopic herniorrhaphy.

PMID- 8560373
TI  - Nitric oxide is an autocrine feedback inhibitor of vascular smooth muscle
      contraction.
AB  - BACKGROUND: Substances that increase intracellular calcium ([Ca2+]i), such as
      potassium chloride and serotonin, are known to induce vascular smooth muscle
      (VSM) contraction. One form of nitric oxide synthase, which converts L-arginine
      to nitric oxide, exists as a Ca(2+)-calmodulin dependent enzyme. The objective of
      this study was to determine whether agonists that induce VSM contraction by
      increasing [Ca2+]i might also activate Ca(2+)-calmodulin dependent nitric oxide
      synthase in VSM. METHODS: Strips of bovine carotid arterial smooth muscle denuded
      of endothelium were equilibrated in a physiologic muscle bath. A maximal
      contractile response to high extracellular potassium chloride and serotonin was
      established. The strips were then preincubated with NG-monomethyl-L-arginine (L
      NMMA), a structural analog of L-arginine and specific inhibitor of nitric oxide
      synthase, and again treated with either KCl or 5-hydroxytryptamine. RESULTS: The
      contractile responses of muscle strips to KCl or 5-hydroxytryptamine were
      significantly greater in muscle strips pretreated with L-NMMA than responses in
      the absence of L-NMMA (p < 0.02, Student's t test). To determine whether this
      response was Ca2+ dependent, phorbolester-induced contractions in Ca(2+)-free
      conditions were examined. No difference was noted in the magnitude of Ca(2+)
      free, phorbol ester-induced contractions in the presence and absence of L-NMMA.
      CONCLUSIONS: These data thus suggest that Ca(2+)-calmodulin dependent nitric
      oxide synthase is functionally present in VSM and may function as an autocrine
      regulatory mechanism of VSM contraction.

PMID- 8560375
TI  - Islet cell carcinoma treated by induction regional chemotherapy and radical total
      pancreatectomy with liver revascularization and small bowel autotransplantation.

PMID- 8560376
TI  - Reform in academic health centers.

PMID- 8560377
TI  - Training of care givers for our aging population.
AB  - We cannot rely on geriatricians, internists, and family practitioners alone in
      the medical community to provide all of the geriatric care. Even though there are
      alternatives to the use of specialists, we cannot afford to ignore the largest
      group of current physician trainees who will provide a great deal of geriatric
      medical care in the future. We need to help make the basic principles of
      geriatric care part of every training program for every resident, whether in
      general or specialty programs.

PMID- 8560378
TI  - Staging of resectable colorectal liver metastases.

PMID- 8560379
TI  - Adequacy of stereotaxic breast biopsies.

PMID- 8560380
TI  - Advanced age alone does not suppress anastomotic healing in the intestine.
AB  - BACKGROUND: Because retrospective clinical studies yield conflicting results and
      experimental data are completely absent, this study was performed to determine
      whether anastomotic repair in the intestine deteriorates with age. METHODS: Ileal
      and colonic anastomoses were constructed in two groups of healthy rats, ages 2 to
      3 months and 27 to 30 months, respectively. Healing was assessed, both 3 and 7
      days after operation, by measuring anastomotic bursting pressure, breaking
      strength, and collagen content, the latter both biochemically (hydroxyproline)
      and morphometrically. In addition, the ex vivo collagen synthetic capacities were
      compared. RESULTS: The development of anastomotic strength was similar in young
      and old rats; average strength increased from 3 to 7 days and was never lower in
      the older animals. This was true for both bursting pressure and breaking
      strength. The collagen production capacity was suppressed in the old rats,
      particularly in the ileum (p < 0.05), whereas the synthesis of noncollagenous
      protein remained unaltered. However, this did not result in a reduced
      accumulation of collagen in the anastomotic area--both anastomotic hydroxyproline
      content and the volume percentage of collagen in the actual wound area were
      unchanged. CONCLUSIONS: Advanced age per se does not affect development of
      strength or deposition of collagen during early repair of intestinal anastomoses.

PMID- 8560381
TI  - Experiences of 120 microsurgical reconstructions of hepatic artery in living
      related liver transplantation.
AB  - BACKGROUND: We reviewed 120 microsurgical reconstructions of a hepatic artery in
      living related liver transplantation and discussed the problems encountered.
      METHODS: From January 1991 to July 1994 we performed a series of 105 living
      related liver transplantations on children with end-stage liver disease. Arterial
      reconstruction was performed under the optical field of a continuous zoom
      magnification of approximately 10 times with an operating microscope. RESULTS:
      Twenty-six percent of the graft arteries were less than 2 mm in diameter. The
      time required for an arterial reconstruction was 49.5 +/- 1.8 minutes. In 15 of
      the 31 cases in which there were two graft arteries, two arterial reconstructions
      were required. The caliber differences between the graft artery and the recipient
      artery in 30 instances was dealt with by cutting an undersized artery obliquely
      (17 instances), by fish-mouth method (10 instances), by end-to-side anastomosis
      (1 instance), or by funnelization method (2 instances). In one case we performed
      an intimal dissection of a recipient hepatic artery and substituted a splenic
      artery. Consequently, hepatic arterial thrombosis occurred in only two cases
      (1.7%). CONCLUSIONS: Microsurgical technique has overcome the high risk of
      hepatic arterial thrombosis in cases of fine graft arteries, enabled the
      reconstruction of arteries with caliber difference, and decreased arterial
      complications with its delicate manipulation.

PMID- 8560382
TI  - Anatomy of vasculature of 850 spleen specimens and its application in partial
      splenectomy.
AB  - BACKGROUND: Anatomic knowledge of vasculature of the splenic lobe and segment is
      of great clinical significance in partial resections and transplantation of the
      spleen. METHODS: The methods of two-colored corrosion casting, roentgenography,
      and anatomic dissection were used to evaluate the vasculature of the splenic
      hilum and intraspleen. On this basis splenic lobectomy and segmentectomy were
      performed on 42 patients with traumatized spleens. RESULTS: In the observation of
      850 spleen specimens the spleen showed a single lobar artery in 7 cases (0.8%),
      two lobar arteries in 730 cases (86%), three lobar arteries in 104 cases (12.2%),
      and multiple lobar arteries (i.e., more than three lobar arteries) in 9 cases
      (1%). In a subgroup of 276 specimens 17%, 53%, 24%, 4%, 1%, and 1% of spleen
      specimens had three, four, five, six, seven, and eight segmental arteries,
      respectively. The result from a subgroup of 280 specimens indicated that mean
      percentages of the existence of the superior and inferior polar arteries and of
      the coexistence of both polar arteries were 31.3%, 38.8%, and 13.3%,
      respectively. Relative avascular planes between segments or lobes were seen.
      Basic steps of splenic lobectomy or segmentectomy include mobilization of the
      injured spleen, ligation of vessels in the lobe or segment, transection of the
      splenic parenchyma, and sutures of the cut surface of the remaining spleen. The
      postoperative courses of all 42 patients undergoing partial splenectomy were
      uneventful. No postoperative bleeding and necrosis of the remaining spleen or
      infectious complications were registered. CONCLUSIONS: Anatomically the spleen is
      defined with two primary lobes (the superior lobe and inferior lobe), one
      accessory lobe, and three to five segments. This new classification facilitates
      surgeons to perform partial resections of the spleen and allotransplantation of
      the hemispleen from a living related donor in human beings.

PMID- 8560383
TI  - Progression of postoperative residual medullary thyroid carcinoma as monitored by
      plasma calcitonin levels.
AB  - BACKGROUND: Patients operated on for medullary thyroid carcinoma (MTC) frequently
      have persistent elevated plasma calcitonin concentrations after operation,
      indicating remaining tumor. The plasma calcitonin concentration in a patient with
      MTC roughly reflects the endogenous tumor burden. The only effective treatment
      for MTC is surgical. The decision about whether a patient with persistent MTC
      should have a repeat operation would be influenced by knowledge of the natural
      course of the disease. METHODS: Forty patients with persistently elevated peak
      plasma calcitonin concentrations after thyroidectomy for MTC were monitored for a
      mean of 6 years. Serial determinations of plasma calcitonin levels were obtained
      before and after intravenous injection of calcium and pentagastrin. RESULTS: At
      the first postoperative test 63% of the patients had undetectable basal
      calcitonin values, although their stimulated plasma calcitonin concentrations
      were elevated. The mean annual increase in stimulated plasma calcitonin
      concentrations was 117%, but plasma calcitonin concentrations were stable in
      three patients and decreased in one patient. Five patients are known to have
      experienced distant metastases. CONCLUSIONS: MTC is a progressive disease in most
      patients with persistent hypercalcitoninemia after thyroidectomy. Stimulated peak
      plasma calcitonin levels are more meaningful than basal levels in the serial
      postoperative evaluation of patients with persistent hypercalcitoninemia after
      thyroidectomy for MTC.

PMID- 8560384
TI  - Surgical resection for small hepatocellular carcinoma.
AB  - BACKGROUND: Surgical resection for hepatocellular carcinoma (HCC) can be curative
      in selected patients, particularly in those with a solitary small HCC (s-sHCC; 2
      cm or less in diameter). However, even these patients often have a risk of tumor
      recurrence or death from underlying liver dysfunction. Therefore it is important
      to determine which clinicopathologic features are related to the long-term
      prognosis after resection of s-sHCC. METHODS: Fifty patients with s-sHCC
      underwent partial hepatectomy at our department between 1977 and 1992. Six (12%)
      died of liver failure in hospital after operation. Eight clinicopathologic
      features were examined in the remaining 44 patients with regard to their long
      term prognosis by use of univariate and multivariate analyses. RESULTS: The 1-, 3
      , and 5-year survival rates were 90%, 75%, and 53%, respectively. The
      corresponding disease-free survival rates were 80%, 53%, and 30%, respectively.
      None of the following parameters was significantly related to survival rate or
      disease-free survival rate: presence of vascular invasion or capsular formation,
      the distance of free surgical margin (1 cm or more or not), serum alpha
      fetoprotein level, positive hepatitis B surface antigen, and preoperative
      transarterial embolization. Complicated liver function was the only significant
      factor related to survival rate and disease-free survival rate. CONCLUSIONS: A
      good hepatic reserve is an important factor in treating patients with s-sHCC by
      surgical resection, even for a long-term prognosis. Liver transplantation should
      be considered for patients with severe cirrhosis and s-sHCC, even though a
      curative resection might be possible.

PMID- 8560385
TI  - Conservative management of esophageal leaks by transluminal endoscopic drainage
      of the mediastinum or pleural space.
AB  - BACKGROUND: The management of postoperative leaks into the mediastinum or pleural
      cavities after esophageal surgery yields unsatisfactory results. A recently
      described method, drainage of the mediastinum or pleural cavity through suture
      line defects, has been used in our department with eight patients. METHODS: A
      suction tube was advanced over an endoscopically placed guide wire into the
      abscess from inside the esophagus, and gentle aspiration was used to remove
      saliva and secretions. Intravenous antibiotics and total parenteral nutrition
      were also given. RESULTS: The sepsis was rapidly controlled, and the abscess
      cavity progressively collapsed in all cases. Seven patients recovered and were
      discharged 34 to 61 days after operation; one died of concomitant complications.
      CONCLUSIONS: This method seems promising for the management of intrathoracic
      esophageal leaks.

PMID- 8560386
TI  - Association of rectal prolapse with colorectal cancer.
AB  - BACKGROUND: Although screening for colorectal cancer facilitates earlier
      detection and improves survival, cost-effective screening requires identification
      of patients at high risk for colorectal cancer. Rectal prolapse has not been
      clearly linked to colorectal carcinoma. Whether patients with rectal prolapse
      should be screened for colorectal cancer is therefore unclear. METHODS: We
      retrospectively identified 70 consecutive patients treated for rectal prolapse at
      a community hospital during a period of 16 years and monitored for an average of
      4.4 +/- 2.7 years and 350 patients of similar age treated for chronic unrelated
      conditions in the same institution during a similar period. We determined their
      incidence of colorectal cancer and sought demographic correlates. RESULTS: The
      prevalence of rectosigmoid carcinoma among patients with prolapse was 5.7% during
      the study. Only 1.4% of the comparative group had colorectal cancer. Thus
      patients with rectal prolapse exhibited a 4.2-fold (95% confidence interval, 1.1
      to 16.0) relative risk for colorectal cancer over the comparative group (p <
      0.02). CONCLUSIONS: To the extent to which these patients represent the
      population of patients with rectal prolapse, routine initial screening of
      patients with symptomatic rectal prolapse by use of flexible sigmoidoscopy may be
      appropriate.

PMID- 8560387
TI  - Facts and fiction: the death of Saint Ignatius of Loyola.
AB  - BACKGROUND: The biography of Ignatius of Loyola, the sainted founder of the
      Society of Jesus (the Jesuits), ends with his death in curious circumstances.
      METHODS: A careful search of the available sources written from the time of his
      death in 1556 to the present has reviewed the evidence. RESULTS: The evidence
      does not support the claims for a diagnosis that has been used for four
      centuries. CONCLUSIONS: So-called historical "facts" simply are the opinions of
      historians. Ignatius may have suffered from hyperparathyroidism that led to his
      death rather than from a cholangioportal venous fistula.

PMID- 8560389
TI  - Anatomic study of the bronchial arteries with special reference to their
      preservation during the radical dissection of the upper mediastinum lymph nodes.
AB  - BACKGROUND: The anatomy of the bronchial arteries was studied, with special
      reference to their preservation during the radical dissection of the upper
      mediastinum lymph nodes. METHODS: The bronchial arteries of 71 cadavers were
      studied macroscopically by use of the surgical field of right thoracotomy. The
      small branches difficult to identify macroscopically were described by x-ray
      imaging with digital subtraction angiography. Their anatomic relationship to the
      adjacent organs was observed microscopically. RESULTS: The bronchial arteries
      arising from the intercostal arteries (the intercostobronchial arteries) were
      observed in 66 of 71 cases. By use of the surgical field of right thoracotomy the
      intercostobronchial arteries were easily found and preserved. All cadavers also
      had other bronchial arteries arising from the aorta. These were difficult to
      preserve because of the depth of the surgical field and the location of their
      course in the dissected area. Bronchial arteries had established connection with
      each other via the vascular network in the tracheal proper sheath. India ink
      injected into the intercostobronchial arteries was observed in the tracheal
      proper sheath and the submucosa of the trachea. CONCLUSIONS: Saving the blood
      supply to the trachea is possible with careful preservation of the
      intercostobronchial arteries and the tracheal proper sheath during radical
      dissection of the upper mediastinum.

PMID- 8560388
TI  - Nitric oxide produced by cytokine-activated pulmonary artery smooth muscle cells
      is cytotoxic to cocultured endothelium.
AB  - BACKGROUND: We recently demonstrated that rat pulmonary artery smooth muscle
      (RPASM) generates maximal nitric oxide (NO) when exposed to inflammatory
      cytokines, such as tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma.
      Our hypothesis is that NO produced by cytokine-stimulated RPASM has local
      cytotoxic effects on endothelium. Accordingly, we designed a pulmonary smooth
      muscle and endothelial coculture experiment in which the effects of NO on
      endothelium can be distinguished from the direct effects of cytokines. METHODS:
      RPASM cells were incubated with a mixture of TNF-alpha (500 units/ml) and IFN
      gamma (100 units/ml) for 24 hours. This cytokine mixture was then removed and the
      NO-producing smooth muscle cells were incubated in a coculture transwell system
      with rat pulmonary artery endothelial (RPAE) cells. Subsequent NO production (as
      measured by nitrite concentration in cell supernatants), and the number of viable
      attached endothelial cells were then measured at 48 hours. RESULTS: RPASM
      continued to produce large amounts of NO, in the absence of further cytokine
      stimulation, after a 24-hour exposure to TNF-alpha and IFN-gamma. This RPASM
      generated NO decreased the number of viable attached endothelial cells after 24
      hour RPASM-RPAE coculture by 57%. The competitive stereospecific inhibitor of
      inducible NO synthase (iNOS), NG-monomethyl-L-arginine (NMA), returned the
      inducible NO production to basal levels and reversed the cytotoxic effects on
      endothelial cells. The number of viable attached endothelial cells returned to
      control levels. CONCLUSIONS: The NO produced by cytokine-activated RPASM has
      local cytotoxic effects on RPAE in coculture. Such NO produced in the vasculature
      may be a factor in the origin of acute lung injury under conditions of trauma and
      sepsis.

PMID- 8560390
TI  - Corticosteroids increase blood interleukin-10 levels during cardiopulmonary
      bypass in men.
AB  - BACKGROUND: Interleukin (IL)-10 is a potent antiinflammatory cytokine inhibiting
      the release of tumor necrosis factor--alpha (TNF-alpha) and IL-8 by activated
      macrophages and polymorphonuclear leukocytes. Cardiopulmonary bypass (CPB)
      represents a unique situation where an inflammatory reaction is predictably
      induced. The present study examined the influence of CPB on the release of TNF
      alpha, IL-1 beta, IL-8, and IL-10 and also defined the effects of pretreatment
      with corticosteroids on the release of these cytokines. METHODS: The study
      included 22 patients undergoing coronary artery bypass graft operations,
      including eight control patients and seven patients who received dexamethasone,
      and seven patients who received methylprednisolone 4 hours before the operation.
      Cytokines were measured with the enzyme-linked immunosorbent assay technique
      before treatment, before anesthesia induction, immediately before heparin
      administration, before aorta declamping, 10 minutes and 90 minutes after aorta
      declamping, and 4 hours after the end of CPB. RESULTS: In the control patients
      the TNF-alpha levels and especially the IL-8 levels increased during CPB and
      reached their maximal levels 4 hours after CPB. IL-10 levels rose moderately and
      transiently, reaching peak values 90 minutes after aorta declamping. Notably,
      administration of corticosteroids prevented IL-8 release but increased IL-10
      levels, which were tenfold higher than in the control group 90 minutes after
      aorta declamping (dexamethasone, 271 +/- 128 pg/ml; methylprednisolone, 312 +/-
      213 pg/ml; control, 17 +/- 12 pg/ml, p < 0.05). IL-1 beta was not detected in any
      group of patients. CONCLUSIONS: The present data indicate that IL-10 is released
      together with proinflammatory cytokines during and after CPB and that
      pretreatment with corticosteroids markedly enhances this release. The release of
      IL-10 may play an important role in the antiinflammatory effects of
      corticosteroids.

PMID- 8560391
TI  - Effects of acid aspiration-induced lung injury on left ventricular function.
AB  - BACKGROUND: Acid aspiration-induced acute lung injury (AALI) leads to myocardial
      leukosequestration and edema in rats and hemodynamic depression in dogs, but the
      effects of AALI on left ventricular (LV) function have not been carefully
      studied. METHODS: We examined the effects of 0.1 N HCl administration into the
      lung on LV function, leukosequestration, and edema in pentobarbital-anesthetized,
      atropinized (n = 8), or autonomically blocked (n = 7) dogs. Saline solution was
      administered into the lungs of a control group of autonomically blocked dogs (n =
      6). LV contractility was assessed by end-systolic elastance (EES) and preload
      recruitable stroke work (PRSW). Active relaxation was assessed by the time
      constant of LV pressure decline (tau). RESULTS: AALI resulted in significant (p <
      0.05) decreases in mean arterial pressure and cardiac output and increases in
      pulmonary artery pressure and systemic vascular resistance in atropinized and
      autonomically blocked dogs but not in saline control group. In atropinized dogs
      tau did not change after injury, but EES and PRSW were increased significantly at
      2 and 3 hours after injury, despite significant myeloperoxidase activity and
      extravascular fluid wet-dry weight ratios. EES, PRSW, and tau did not change in
      the autonomically blocked dogs in response to AALI or in the saline control
      group. CONCLUSIONS: We concluded that AALI results in a baroreflex mediated
      enhancement of LV contractility in dogs, despite mild myocardial
      leukosequestration and edema formation.

PMID- 8560392
TI  - Reversibility of deoxycholate-induced cellular hypercalcemia in rabbit gastric
      mucosal cells.
AB  - BACKGROUND: Bile acid exposure produces cellular hypercalcemia in gastric and
      hepatic cells. It is not known, however, whether this event contributes to cell
      injury or if it results from passive equilibration of calcium ion concentrations
      across the membranes of irreversibly damaged cells. This study was performed to
      determine whether the cellular hypercalcemia produced by bile acid exposure in
      gastric cells is reversible and to determine whether the source of this
      hypercalcemia is from intracellular stores of calcium, extracellular sources, or
      both. METHODS: Cytosolic free calcium concentrations ([Ca]i) were measured in
      rabbit gastric mucosal cells that had been loaded with the intracellular probe
      FURA-2. Measurements were performed in suspensions of dispersed cells by using
      standard spectrofluorometry and in primarily cultured cells by using fluorescence
      videomicroscopy. Measurements were made before and after exposure to 0.2, 0.5,
      and 1.0 mmol/L deoxycholic acid (DC). These measurements were made in the
      presence of 1 mmol/L extracellular calcium and in the absence of any
      extracellular calcium (0.5 mmol/L EGTA). RESULTS: In experiments with dispersed
      cells and spectrofluorometry, [Ca]i increased from a pretreatment level of 194 +/
      8 nmol/L to 396 +/- 21 nmol/L within 3 minutes of exposure to 0.2 mmol/L DC.
      When these cells were washed and resuspended in DC-free medium, [Ca]i] decreased
      to 180 +/- 5 nmol/L. In experiments with cultured cells and fluorescence
      videomicroscopy, rapid, reversible hypercalcemia was observed after exposure to
      0.5 and 1.0 mmol/L DC. Removal of extracellular calcium from the incubating
      medium reduced both the magnitude and duration of the observed hypercalcemia.
      CONCLUSIONS: These data show that the cellular hypercalcemia that accompanies DC
      induced injury in gastric cells is a reversible event. The initial increase in
      [Ca]i appears to come from both intracellular and extracellular sources, although
      sustained hypercalcemia requires a source of extracellular calcium. As a
      reversible event, cellular hypercalcemia may be an important pathophysiologic
      feature of bile acid induced injury of the upper gastrointestinal tract.

PMID- 8560393
TI  - Effect of the duration of symptoms, transport time, and length of emergency room
      stay on morbidity and mortality in patients with ruptured abdominal aortic
      aneurysms.
AB  - BACKGROUND: Despite improvements in emergency medical services, surgical
      technology, and postoperative critical care, ruptured abdominal aortic aneurysm
      (AAA) is associated with constantly high morbidity and mortality. To determine
      the effect of the duration of symptoms, transport time to hospital, and length of
      emergency department assessment on outcome, we evaluated 124 consecutive patients
      with ruptured AAA treated during the past decade. METHODS: The medical records
      for 122 patients were abstracted for preoperative hypotension, cardiopulmonary
      resuscitation (CPR), blood loss, and three time intervals: symptom onset to
      operation, transport time to hospital, and emergency department assessment.
      RESULTS: Intraoperative mortality was 26% (n = 32), 30-day mortality was 51% (n =
      63), and cumulative hospital mortality was 56% (n = 69). Death occurred in 52
      (64%) of 81 patients with hypotension compared with 14 (35%) of 40 patients
      without hypotension (p < or = 0.01). Hypotension was present in 37 (82%) of 45
      patients who arrived in the operating room in 2 hours or less compared with 26
      (60%) of the 43 patients who arrived later than 2 hours (p < or = 0.05). Death
      followed in 21 (91%) of 23 patients who received CPR compared with 46 (46%) of 99
      patients who did not receive CPR (p < or = 0.01). Bowel ischemia was observed in
      18 (30%) of 60 patients who received more than 10 units of blood compared with 3
      (5%) of 61 patients who received 10 units or less (p < or = 0.01). CONCLUSIONS:
      For patients with ruptured AAA, prolonged presurgical time was associated with a
      more hemodynamically stable patient and a lower mortality. Progressive bleeding
      in those hemodynamically stable patients was reflected by a larger blood
      transfusion requirement. Such patients exhibited an increased incidence of
      ischemic bowel complications, perhaps caused by splanchnic arterial ischemia
      augmented by preexisting atherosclerosis, as well as extrinsic compression by
      mesenteric hematomas.

PMID- 8560394
TI  - Mechanistic imbalance of pulmonary vasomotor control in progressive lung injury.
AB  - BACKGROUND: Pulmonary hypertension is the major hemodynamic feature of
      progressive lung injury. We hypothesized that the mechanisms of pulmonary
      vasorelaxation become progressively impaired in progressive lung injury. The
      purpose of this study was to examine the following mechanisms of pulmonary
      vasorelaxation in a rat model of monocrotaline-induced progressive lung injury:
      endothelial-dependent cyclic guanosine monophosphate-mediated relaxation
      (response to acetylcholine), endothelial-independent cyclic guanosine
      monophosphate-mediated relaxation (response to nitroprusside), beta-adrenergic
      cyclic adenosine monophosphate-mediated relaxation (response to isoproterenol),
      and hypoxic pulmonary vasoconstriction. METHODS: Rats were studied 2, 7, and 14
      days after monocrotaline injection (100 mg/kg intraperitoneally). Pulmonary
      vasomotor control mechanisms were studied in isolated pulmonary artery rings.
      Controls were studied 14 days after saline injection. Statistical analysis was by
      ANOVA; p < 0.05 was considered significant. RESULTS: A progressive impairment of
      pulmonary vasorelaxation was observed. By 14 days after monocrotaline injection
      acetylcholine produced only 25% +/- 5% relaxation versus 95% +/- 5% in controls
      (p < 0.05), nitroprusside produced 46% +/- 5% relaxation versus 100% in controls
      (p < 0.05), and isoproterenol produced only 18% +/- 5% relaxation versus 94% +/-
      4% in controls (p < 0.05). At the same time hypoxic pulmonary vasoconstriction
      became progressively exaggerated. CONCLUSIONS: Progressive dysfunction of
      pulmonary vasomotor control may contribute to the pulmonary hypertension seen in
      progressive lung injury.

PMID- 8560395
TI  - The validity of four methods for age determination by teeth in Swedish children:
      a multicentre study.
AB  - Four principally different methods for age determination of children by means of
      teeth have been tested on a Swedish population. 197 panoramic radiographs of
      children aged 5, 6, 9 and 12 years were collected and examined by 13 independent
      pedodontists, radiologists and forensic odontologists. The results showed a
      satisfactory precision for those methods which have been developed on a
      Scandinavian population, but a method from a French-Canadian population showed a
      consistent over-estimation when used on the Swedish children.

PMID- 8560396
TI  - Effects of static magnetic fields on human periodontal fibroblasts in vitro.
AB  - In orthodontic treatment, the use of mechanical forces generated by magnetic
      fields have increased significantly over the past years, triggered by the
      introduction of rare earth permanent magnetic alloys. Rare earth magnets,
      initially made from cobalt-samarium alloy and later from neodymium-iron-boron
      alloy generate high mechanical forces in relation to their small size. Relating
      to their use in orthodontic treatment, queries about possible side effects have
      been expressed. This study was undertaken in order to determine if cell growth
      and attachment in vitro is affected over time in a static magnetic field of a
      magnitude comparable to that used clinically. Significantly and progressively
      impaired attachment and growth over a 5 week period was observed when human
      periodontal fibroblasts were cultured in a static magnetic field. These results
      indicate that a static magnetic field itself is capable of influencing vital cell
      functions, although they do not exclude the possibility of corrosion products
      from the magnets contributing to previously observed cytotoxic in vitro and
      biological in vivo effects.

PMID- 8560397
TI  - Linear unsharp mask filtering of linear cross-sectional tomograms of the
      posterior mandible.
AB  - Linear unsharp mask filtering is a digital image processing technique which can
      enhance diagnostic information by subtracting from the original image the linear
      blur which was formed in the direction of the linear tomographic movement. It was
      applied to linear cross-sectional tomograms of the posterior mandible aiming at
      retrieving cross-sectional outline information. This study demonstrated that the
      current Orthophos Program 16 with a 6.72 degrees tomographic angle does not
      provide accurate cross-sectional outline information of the posterior mandible.
      Linear unsharp mask filtering of these images also failed to provide more
      information. A larger tomographic angle of 10 degrees was employed with the
      Polytome to simulate the modified Program 16 with a wider beam. The resulting
      tomographic images showed better defined cross-sectional outlines, and after the
      linear unsharp mask filtering, the outlines were more readily retrieved. In order
      to get cross-sectional outline information of the posterior mandible, the
      tomographic angle of the Orthophos program 16 should be increased to more than 10
      degrees which can be achieved by increasing the width of the x-ray beam.

PMID- 8560398
TI  - The reproducibility and the validity of landmarks for the antero-inferior part of
      the maxilla in radiographic cephalometry.
AB  - Two possible landmarks, C1 and C2, were evaluated as alternatives to the A point
      (subspinale), in lateral radiographic cephalometry. The landmarks were determined
      on tracings of 25 straight lateral radiographs. Horizontal and vertical
      coordinates were recorded for C1 and C2, and also for point A, and the incisor
      edge and apex. The reproducibilities of the landmarks were determined by
      statistical analyses of the differences between landmark determinations on
      repeated tracings. Regression analyses were used to evaluate the validity of
      measurements on C1 and C2 in relation to corresponding measurements on the A
      point. In addition, the influences of upper incisor inclinations and of alveolar
      process inclinations on validity were investigated by regression analyses and
      analytical geometry, respectively. The reproducibility of all landmarks including
      C1 and C2 was high (correlation coefficients above 0.985). Both C1 and C2 were
      strongly correlated with point A (adjusted R2 values from 82 to 85 per cent). The
      inclination of the lingual aspect of the alveolar process may change from an
      alteration of the incisor inclination. When this happens, the positional change
      of C2 horizontally is smaller than the change of C1. Therefore, C2 appears to be
      the more valid landmark for horizontal measurements. The designation suggested
      for this landmark is C.

PMID- 8560399
TI  - The use of time study results in a system model for presenting dental care
      outcome.
AB  - The documentation of dental care outcome and dental clinic efficiency is based on
      variables for the patient's dental health and on resources in time and costs
      concerning the dental treatment. The aim of this paper was to measure dental
      clinic activities using a time study method in relation to a model for a system
      for presenting dental care outcome, and the dental clinic's output and
      efficiency. For efficiency reporting of dental care related effects, the
      documentation should be based on rules for input costs related to dental clinic
      activities, based on valid country-wide criteria for work times of the dental
      personnel; dental care economics; and current epidemiological indices. Additional
      use of results from time studies made it possible to adapt the need of resources
      in dental care, and to obtain essential information concerning the choice of
      dental team models. For reporting, a dental health related patient group system,
      based on the patients' dental health and need of dental treatment, should be
      used. In the proposed model for a system for presenting dental care, knowledge of
      patients, and of what services the dental personnel can perform was used.

PMID- 8560400
TI  - The fundamental theorem of natural selection in Ewens' sense (case of many loci).
AB  - We correct an equation characterizing the additive allelic effects on fitness
      determined at many loci without the assumption of random mating given in Ewens
      (1989, 1992) and we show that the additive genetic variance in fitness divided by
      the mean fitness is equal to a partial change in the mean fitness from one
      generation to the next as stated in Ewens (1989).

PMID- 8560401
TI  - Protein C Osaka 10 with aberrant propeptide processing: loss of anticoagulant
      activity due to an amino acid substitution in the protein C precursor.
AB  - We studied the molecular basis of protein C deficiency in a family with a history
      of thromboembolic disease. An approximately 50% reduction in anticoagulant
      activity despite normal levels of protein C amidolytic activity and antigen was
      detected in plasma from the proband. All the exons and intron/exon junctions of
      the protein C gene were studied using a strategy that combined polymerase chain
      reaction amplification with DNA sequencing of the amplified fragments. We
      identified a C-to-A change at nucleotide number 1387 of the protein C gene in the
      proband and his mother, and this mutant was designated protein C Osaka 10. The C
      to-A change resulted in the substitution of Ser for Arg at position -1, which is
      the processing protease cleavage site. The mutant protein C was partially
      purified from plasma of the patient's mother using barium adsorption followed by
      ion-exchange column chromatography. It eluted at the same sodium chloride
      concentration as normal protein C, and thus gamma-carboxylation of the mutant
      protein appeared to be normal. The apparent molecular weight of this mutant
      protein C was the same as that of the normal protein on immunoblotting. Amino
      terminal sequence analysis showed that the light chain of the mutant protein C
      had an additional Ser at position-1. Thus, the loss of anticoagulant activity of
      protein C Osaka 10 can be explained by alteration of the conformation of the Gla
      domain by the additional Ser in the mutant molecule.

PMID- 8560402
TI  - Diagnosis of hemophilia B carriers using two novel dinucleotide polymorphisms and
      Hha I RFLP of the factor IX gene in Japanese subjects.
AB  - We identified two novel dinucleotide polymorphisms in intron A at nucleotide 192
      (FIX192) and in the 5' flanking region at nucleotide -793 (FIX-793) of the factor
      IX gene, which are present in normal Japanese. The Hha I restriction fragment
      length polymorphism (FIX-HhaI) located 8 kb 3' to the factor IX gene was also
      found to be an efficient marker for detecting carriers in a Japanese family with
      hemophilia B. Each of these polymorphisms was able to be rapidly ascertained by
      the polymerase chain reaction (PCR) technique. In 22 Japanese families with
      hemophilia B, 18 families (81.8%) were heterozygous for at least one of these
      polymorphisms, whereas 11 (50%) were informative for the extragenic DXS99/Sac I
      RFLP which was previously reported as a useful gene marker for Japanese
      hemophilia B. Using all 4 polymorphisms together, the informative rate improved
      to 86.4%. Carrier detection and, possibly, the prenatal diagnosis of hemophilia B
      can be achieved effectively and rapidly in Japanese with these polymorphisms.

PMID- 8560403
TI  - Thromboxane biosynthesis, neutrophil and coagulative activation in type IIa
      hypercholesterolemia.
AB  - Thromboxane (Tx) A2 biosynthesis is enhanced in the majority of patients with
      type IIa hypercholesterolemia. Because blood clotting activation is an important
      component of the inflammatory response, involved in the initiation and
      progression of atherosclerotic plaques, we have investigated TxA2 biosynthesis,
      neutrophil activation and thrombin generation in 24 patients with type IIa
      hypercholesterolemia. Urinary 11-dehydro-TxB2, was significantly higher (p =
      0.0001) in patients than in 24 sex- and age matched healthy subjects. Similarly,
      prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complexes and
      plasma elastase were significantly higher in patients than in controls. Urinary
      11-dehydro-TxB2 excretion was correlated with plasma elastase (r = 0.758; p =
      0.0001), and prothrombin fragment 1 + 2 (r = 0.804; p = 0.001). The enzyme 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (20 mg/day
      for 2 months) significantly reduced cholesterol levels, urinary 11-dehydro-TxB2
      excretion, plasma elastase and plasma F1 + 2 in 8 patients. We conclude that type
      IIa hypercholesterolemia is associated with biochemical evidence of platelet,
      neutrophil and blood clotting activation. The relationship between these events
      remains to be investigated.

PMID- 8560404
TI  - High lipoprotein (a) levels in chronic hemodialysis patients are closely related
      to the acute phase reaction.
AB  - To study the mechanism underlying the high lipoprotein (a) [Lp(a)] level in
      uremic patients on chronic hemodialysis, we investigated the levels of Lp(a),
      acute phase reactants (C-reactive protein and sialic acid), and interleukin-6 (IL
      6) in 54 dialysis patients. The mean [95% CI] Lp(a) level was increased in the
      hemodialysis patients compared with the 30 controls (30 [25-36] vs. 18 [14-23]
      mg/dl, p < 0.005). Among dialysis patients, 46% had an Lp(a) level > 30 mg/dl,
      which was significantly higher than the percentage in the control group (17%).
      The levels of C-reactive protein, sialic acid, and IL-6 were also increased in
      dialysis subjects compared with controls (200 [134-299] vs. 37 [24-58]
      micrograms/dl, p < 0.0001; 63 [59-66] vs. 54 [52-56] mg/dl, p < 0.002; and 9.2
      [7.8-11] vs. 5.5 [5.0-6.1] pg/ml, p < 0.0005, respectively). The Lp(a) level was
      positively correlated with that of C-reactive protein (r = 0.415, p < 0.002),
      sialic acid (r = 0.426, p < 0.002), and IL-6 (r = 0.298, p < 0.05) in the
      hemodialysis patients, but not in the controls or non-dialysis uremic patients.
      The Lp(a) level in the dialysis patients was also positively correlated with
      activation markers of coagulation (thrombin-antithrombin III complex and plasmin
      alpha 2-plasmin inhibitor complex, p < 0.005). These results indicate that the
      Lp(a) level is closely related to the acute phase reaction and hypercoagulability
      in chronic hemodialysis patients.

PMID- 8560405
TI  - Influence of various heparin preparations on lipoproteins in hemodialysis
      patients: a multicentre study.
AB  - Recent studies have indicated controversial effects of low molecular weight
      heparin (LMWH) on lipid metabolism in patients on chronic hemodialysis as
      compared to unfractionated heparin (UFH). We therefore conducted a cross
      sectional multicentre study comparing 153 patients treated with LMWH and 153
      patients with UFH, matched for sex, age and diabetes mellitus. Both groups have
      been treated with LMWH or UFH for six months or longer (14.9 vs. 23.4 months). We
      observed no differences between the UFH and LMWH treatment groups for total
      cholesterol, LDL cholesterol, triglycerides, apoB, apoA-IV or Lp(a). The only
      significant differences were seen for HDL cholesterol and the corresponding
      apolipoprotein apoA-I, which were significantly higher in the UFH group (HDL
      cholesterol: 0.97 +/- 0.35 mM/l vs. 0.87 +/- 0.37 mM/l, p < 0.05; apoA-I 1.23 +/-
      0.27 g/l vs. 1.15 +/- 0.27 g/l, p < 0.05). We conclude that the results of
      studies investigating the influence of LMWH on lipid metabolism are as
      heterogeneous as the substances themselves. This challenges the beneficial
      influence supposedly had by LMWH preparations on lipid metabolism.

PMID- 8560406
TI  - The factor V Leiden mutation which predisposes to thrombosis is not common in
      patients with antiphospholipid syndrome.
AB  - Antiphospholipid syndrome is associated with venous, arterial, and placental
      thrombosis, possibly through autoantibody impairment of phospholipid-dependent
      protein C activation. Recently, a missense mutation in the factor V gene (1691 G-
      >A) has been identified that results in an abnormal factor V product (1). This
      mutation, known as the Leiden mutation, causes an amino acid substitution of
      glutamine for arginine at position 506 in the factor V molecule and renders the
      protein resistant to proteolytic inactivation by activated protein C and thus
      predisposes to thrombosis (2, 3). We hypothesized that some individuals with
      antiphospholipid syndrome may also carry the Leiden mutation, and thus have a
      "second hit" predisposition to thrombosis. To test this hypothesis, allele
      specific hybridization and allele-specific restriction analysis were used to test
      for the Leiden mutation in thirty women with the antiphospholipid syndrome, 10 of
      whom had a history of thrombosis. None of the women were heterozygous or
      homozygous for the factor V mutation. We conclude that the presence of the factor
      V Leiden mutation is not a prerequisite for the thrombotic events in patients
      with antiphospholipid syndrome, due to the occurrence of thrombosis seen in
      patients lacking the factor V mutation.

PMID- 8560407
TI  - Plasminogen activator inhibitor-1 (PAI-1) promoter polymorphism and coronary
      artery disease in non-insulin-dependent diabetes.
AB  - Elevated levels of PAI-1 are found in coronary artery disease (CAD) and non
      insulin-dependent diabetes (NIDDM). PAI-1 may be involved in the pathogenesis of
      CAD through suppression of fibrinolysis, alternatively the high levels may result
      from vascular damage. There is evidence that PAI-1 levels are related to genotype
      at a PAI-1 promoter polymorphism. Genotype at this 4G/5G polymorphism was
      determined in 160 NIDDM (90 males and 70 females) patients with (n = 38) or
      without (n = 122) clinical evidence of CAD. Levels of cholesterol were higher
      (6.5 vs 5.9 mM, p < 0.01) and PAI-1 tended to be higher (PAI-1 activity 23.0 vs
      20.4 U/ml) with CAD. The frequency of the 4G/4G genotype was increased and the
      5G/5G genotype decreased, in the group CAD compared to those without (p < 0.05).
      These results suggest that possession of the 4G/4G PAI-1 promoter genotype is a
      risk factor for the development of CAD in subjects with NIDDM.

PMID- 8560408
TI  - Elimination of acquired factor VIII antibodies by extracorporal antibody-based
      immunoadsorption (Ig-Therasorb).
AB  - Treatment of potent factor VIII antibodies is a difficult problem. In some cases
      a reduction of the antibody titer is necessary for effective treatment with human
      factor VIII concentrates. We describe a new method for extracorporal elimination
      of factor VIII antibodies (antibody-based immunoadsorption). Blood is drawn from
      an antecubital vein, citrated, and plasma is separated with a rotating membrane.
      Plasma passes alternately through one of two columns filled with sepharose
      coupled polyclonal sheep antibodies to human immunoglobulins (Ig-Therasorb),
      whereas the other column is regenerated. Each cycle has a duration of 15 min.
      Three patients with high titer factor VIII antibodies (one hemophiliac and 2 with
      spontaneous antibodies; titers 29, 132, and 313 BU/ml, respectively) were
      treated. The average reduction of the antibody titer was 76.1 +/- 17.2% per
      session. In each patient 4 sessions were necessary to reduce the antibody titer
      to < 1 BU/ml. The mean processed plasma volume was 6731 +/- 640 ml and the mean
      duration of each session 3.9 +/- 0.7 h. Serum IgG, IgA and IgM levels decreased
      by 75.3 +/- 11.9%, 62.9 +/- 19.1%, and 54.8 +/- 23.8% respectively. The procedure
      was tolerated without any side effects. Thus, rapid elimination of factor VIII
      inhibitors can be achieved with antibody-based immunoadsorption, which can be
      life-saving in some cases. This promising method should be evaluated in a larger
      number of patients.

PMID- 8560409
TI  - Induction of immune tolerance in a 7-year-old hemophiliac with an anaphylactoid
      inhibitor.
AB  - BACKGROUND: Anaphylactic reactions were a rare complication of low purity VIII
      concentrates, but not with high purity VIII concentrates. CASE: 7 y/o WM with
      severe hemophilia A, received only cryoprecipitate and monoclonally purified VIII
      concentrates; developed post-infusional urticaria. A 2-Bethesda-unit inhibitor
      was detected. Generalized urticaria and bronchospasm following factor developed
      as the titer increased. Skin tests demonstrated reactivity to plasma derived
      VIII, but not recombinant VIII (rhVIII). Attempts at desensitization using rhVIII
      failed. ELISA revealed an anti-VIII IgE antibody. He was treated with a modified
      tolerance regimen using rhVIII starting at 500 U/day with aggressive
      premedication. The dosage increased by 200 U weekly as tolerated to a maximum of
      100 U/kg/d without symptoms. RESULTS: His antibody titer decreased rapidly once
      he started 100 U/kg/d. Six months later, the inhibitor was < 1 Bethesda unit.
      CONCLUSION: Immune tolerance induction using a graduated dosage of rhVIII was
      successful.

PMID- 8560410
TI  - Clinical outcome of orthopaedic patients with negative lower limb venography at
      discharge.
AB  - Pharmacological prophylaxis for postoperative venous thromboembolism is generally
      restricted to the hospital stay. A high incidence of deep vein thrombosis (DVT)
      and pulmonary embolism presenting after hospital discharge has been reported and
      thus it has been claimed that pharmacological prophylaxis should be continued
      after discharge. The aim of this study was to perform a prospective survey to
      assess the prevalence of clinically overt thromboembolic events in hip surgery
      patients discharged with a negative venography without further pharmacological
      prophylaxis. We followed-up 213 patients with negative venography at discharge
      (105 elective hip replacement and 108 hip fracture patients). 186 patients
      (87.3%) were re-examined as outpatients one to two months after discharge. Five
      patients reported symptoms of DVT but the diagnosis was not confirmed by
      objective testing. The remaining 27 patients (12.7%) were followed up through
      their family doctor or by telephone call; in these patients the follow-up period
      ranged from 60 days to 2 years. Twenty-two patients (10.3%) were still alive and
      reported no signs or symptoms of venous thromboembolism. Three patients (1.4%)
      died for reasons not correlated with venous thromboembolism. Two patients could
      not be traced due to geographical inaccessibility; they were still alive after 1
      year according to the records of their health care district. The results of our
      study suggest that in hip surgery patients with negative venography the
      prevalence of clinically overt thromboembolic events after hospital discharge
      ranges from 0 to 2.2% (95% C.I.). It is conceivable that the majority of late
      presenting postoperative DVT actually develop during the hospital stay and become
      symptomatic after hospital discharge.

PMID- 8560411
TI  - Alterations in vascular endothelial cell-related plasma proteins in thalassaemic
      patients and their correlation with clinical symptoms.
AB  - An increased level of plasma thrombomodulin (TM) in alpha- and beta-thalassaemia
      was demonstrated using an enzyme-linked immunosorbent assay (ELISA).
      Nonsplenectomized patients with beta-thalassaemia/haemoglobin E (BE) had higher
      levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU)
      were found to have the highest increase in TM level. Appearance of larger
      platelets in all types of thalassaemic blood was observed indicating an increase
      in the number of younger platelets. These data indicate that injury of vascular
      endothelial cells is present in thalassaemic patients.

PMID- 8560412
TI  - Decreased plasma tissue factor pathway inhibitor activity in ischemic stroke
      patients.
AB  - Although tissue factor pathway inhibitor (TFPI) plays an essential role in the
      regulation of blood coagulation, the quantitative changes in its levels in
      thrombotic disease are still undefined. We compared TFPI activity in ischemic
      stroke patients and control subjects matched for age and cholesterol level to
      determine whether TFPI activity is changed in the disease. TFPI activity was
      significantly lower in the stroke patients (1.01 +/- 0.24 U/ml) than in the
      control subjects (1.10 +/- 0.16 U/ml). In relation to clinical subtypes of
      stroke, TFPI activity in atherothrombotic infarction (0.93 +/- 0.19 U/ml) and
      lacunar infarction (0.99 +/- 0.23 U/ml) was significantly lower than in the
      control subjects, whereas the level in cardioembolic infarction (1.16 +/- 0.31
      U/ml) was not. No relationship could be established between TFPI activity and
      other haemostatic parameters reflecting the production of thrombin/fibrin and the
      activation of fibrinolysis. These results may suggest that the moderately lower
      TFPI activity in stroke patients could be due to atherosclerotic changes rather
      than to consumptive coagulopathy.

PMID- 8560413
TI  - The efficacy and safety of oral anticoagulation in patients with cancer.
AB  - OBJECTIVES: To compare the complication rate (bleeding and thrombosis) of oral
      anticoagulation in a cohort of patients with cancer to a cohort without cancer.
      DESIGN: Prospective cohort study. SETTING: Outpatient anticoagulation clinic in a
      community hospital. PATIENTS: Consecutive patients enrolled in an anticoagulation
      clinic: 44 with cancer, 64 without cancer. INTERVENTIONS: Patients received
      prophylactic doses of Warfarin (target INR 2-3 in the majority of instances) and
      complication rates were assessed. MEASUREMENTS: Major bleeding (strictly
      defined), minor bleeding, recurrent thrombosis, proportion of time with
      therapeutic INR, frequency of clinic visits. RESULTS: The rates of major
      bleeding, minor bleeding, and recurrent thrombosis were not statistically
      significantly different in the two groups of patients. Therapeutic INR's were
      more difficult to sustain in the cancer patients as compared to the non-cancer
      patients (43.3% vs 56.9%, p < 0.0001). There was a non significant trend towards
      more frequent monitoring for the cancer patients compared with the non-cancer
      patients (4.6 vs 3.5 visits per treatment month, p = 0.14). CONCLUSIONS: Oral
      anticoagulation is safe and effective in the patient with cancer. It is more
      difficult to sustain a therapeutic INR in the cancer patients and they may need
      more frequent monitoring to achieve a low complication rate.

PMID- 8560414
TI  - Flow cytometric detection of activated platelets in pregnant women prior to the
      development of pre-eclampsia.
AB  - Pre-eclampsia is a common complication of pregnancy, in which platelets may have
      an early pathogenetic role. In this prospective study a whole blood flow
      cytometric method has been used to detect circulating activated platelets in
      pregnant women prior to the development of pre-eclampsia. Activated platelets
      were identified by bound fibrinogen or by CD63 antigen expression. Of 121 healthy
      primiparous women studied at 28 weeks of pregnancy, 18 (15%) developed clinical
      pre-eclampsia six to thirteen weeks later. The platelets of these women showed
      increased fibrinogen binding ex vivo (5.1% platelets positive, compared with 3.4%
      in those who completed a normal pregnancy, p < 0.02), and increased CD63 antigen
      expression (0.73% positive compared to 0.45%, p = 0.01). In contrast, no
      differences between the women with different outcomes were detected at 28 weeks
      in platelet counts, or plasma beta-thromboglobulin levels. These findings confirm
      that whole blood flow cytometry is a sensitive technique for investigating
      platelet activation in a clinical setting and support the hypothesis that
      platelets have a critical role in the pathogenesis of pre-eclampsia.

PMID- 8560415
TI  - The effect of desmopressin on reducing blood loss in cardiac surgery--a meta
      analysis of double-blind, placebo-controlled trials.
AB  - The effect of desmopressin (DDAVP) on reducing postoperative blood loss after
      cardiac surgery has been studied in several randomized clinical trials with
      conflicting outcomes. Since most trials had insufficient statistical power to
      detect true differences in blood loss, we performed a meta-analysis of data from
      relevant studies. Seventeen randomized, double-blind, placebo-controlled trials
      were analyzed, which included 1171 patients undergoing cardiac surgery for
      various indications; 579 of them were treated with desmopressin and 592 with
      placebo. Efficacy parameters were blood loss volumes and transfusion
      requirements. Desmopressin significantly reduced postoperative blood loss by 9%,
      but had no statistically significant effect on transfusion requirements. A
      subanalysis revealed that desmopressin had no protective effects in trials in
      which the mean blood loss in placebo-treated patients fell in the lower and
      middle thirds of distribution of blood losses (687-1108 ml/24 h). In contrast, in
      trials in which the mean blood loss in placebo-treated patients fell in the upper
      third of distribution (> 1109 ml/24 h), desmopressin significantly decreased
      postoperative blood loss by 34%. Insufficient data were available to perform a
      sub-analysis on transfusion requirements. Therefore, desmopressin significantly
      reduces blood loss only in cardiac operations which induce excessive blood loss.
      Further studies are called to validate the results of this meta-analysis and to
      identify predictors of excessive blood loss after cardiac surgery.

PMID- 8560416
TI  - Mechanisms of platelet dysfunction and response to DDAVP in patients with
      congenital platelet function defects. A double-blind placebo-controlled trial.
AB  - To examine the impact of the underlying defective platelet mechanism on the
      response to 1-desamino-8-D-arginine vasopressin (DDAVP, Desmopressin), we studied
      the effect of intravenous infusion of 0.3 microgram/kg of DDAVP in a randomized
      double blind placebo-controlled trial with cross-over in 18 carefully
      characterized patients with congenital platelet defects (CPD) and BT > or = 9
      min. Eleven patients had normal dense granule stores and normal thromboxane A2
      (TxA2) production (Group I), 3 patients had normal granule stores but impaired
      TxA2 production (Group II), and 4 had delta-storage pool deficiency (Group III).
      DDAVP shortened BT at 50 min (DDAVP 14.6 +/- 2.2 vs placebo 19.6 +/- 2.3 min; n =
      18; mean +/- SE; p = 0.003) and 4 h (17.0 +/- 2.2 vs 19.6 +/- 2.1 min, p =
      0.055), and raised plasma FVIIIC and von Willebrand factor (vWF). At 50 min DDAVP
      shortened BT by > or = 5 min in 8 of 11 Group I patients (mean 9.7 +/- 1.3 vs
      16.3 +/- 2.8 min; p < 0.008), 1 of 3 Group II patients (11.9 +/- 3.9 vs 17.7 +/-
      6.6; p = NS) and none of Group III patients (mean 30 min both arms). Ten patients
      (Group I or II) were managed successfully during surgical procedures with DDAVP
      alone. We conclude that DDAVP shortens BT in majority of CPD patients with normal
      dense granule stores and suggest that BT response may be dependent on the
      underlying platelet defect. DDAVP is a useful modality in management of selected
      patients, particularly those with normal dense granule stores.

PMID- 8560417
TI  - Characterization of a cDNA for rhesus monkey protein C inhibitor--evidence for N
      terminal involvement in heparin stimulation.
AB  - cDNAs for protein C inhibitor (PCI) were cloned from human and rhesus monkey
      liver RNAs by reverse transcription and polymerase chain reaction (PCR)
      amplification. Sequencing showed that rhesus monkey and human PCI cDNAs were 93%
      identical. Predicted amino acid sequences differed at 26 of 387 residues. Four of
      these differences (T352M, N359S, R362K, L363I) were in the reactive center loop
      that is important for inhibitory specificity, and two were in the N-terminal
      helix (M8T, E13K) that is implicated in glycosaminoglycan binding. PCI in human
      or rhesus monkey plasma showed comparable inhibitory activity towards human
      activated protein C in the presence of 10 U/ml heparin. However, maximal
      acceleration of the inhibition of activated protein C required 5-fold lower
      heparin concentration for rhesus monkey than for human plasma, consistent with
      the interpretation that the additional positive charge (E13K) in a putative
      heparin binding region increased the affinity for heparin.

PMID- 8560418
TI  - Conformational changes in low molecular weight kininogen alters its ability to
      bind to endothelial cells.
AB  - The plasma kininogens, high (HK) and low (LK) molecular weight kininogens, are
      the parent proteins for bradykinin, a potent vasoactive peptide that locally
      influences vascular biology. Binding of both HK and LK to the endovascular wall
      contributes to bradykinin delivery. Recently, we found one preparation of LK
      (LKd) which had reduced inhibition of biotin-HK binding to endothelium. The
      functional defect in LKd was not merely due to bradykinin loss because two
      preparations of bradykinin-free LK blocked biotin-HK binding. However, using two
      different particular monoclonal antibodies to bradykinin, LKd, but no other
      preparation of LK, had its epitope to bradykinin exposed on non-reduced samples
      on immunoblot. These data suggested that LKd had an altered conformation which
      exposed the amino terminal arginine of bradykinin to antigenic detection. The
      altered conformation of LKd allowed it to be more susceptible to trypsin
      proteolysis. On circular dichroism, the percentage of alpha-helix was
      significantly increased, indicating an alteration in the protein. This alteration
      in LKd was not due to a loss of molecular mass of the protein. On laser
      desorption mass spectroscopy, the molecular mass of LKd was similar to the other
      preparations of LK. Investigations were performed to ascertain the mechanism by
      which LKd had altered ability to bind to cells. LKd was found to be proteolyzed
      by an unknown protease at the beginning of domain 2 between threonine119 and
      alanine120. Reduction of functional LK with dithiothreitol to expose its
      bradykinin epitope did not produce the LKd defect. Proteolysis of functional LK
      with plasma kallikrein, elastase followed by plasma kallikrein, chymotrypsin, or
      bromelain also did not produce the defect seen in LKd. These combined data
      indicated that LK maintains a particular conformation that allows the protein to
      orient itself such that it can bind to endothelial cells. Proteolysis in the
      surface exposed region between domains 1 and 2 probably allows for the protein to
      unfold and contributes to its lost ability to bind to endothelial cells.

PMID- 8560419
TI  - Tissue factor expression on mesothelial cells is induced during in vitro culture-
      manipulation of culture conditions creates perspectives for mesothelial cells as
      a source for cell seeding procedures on vascular grafts.
AB  - Lining the luminal surface of prosthetic small diameter bypasses with endothelial
      cells (EC) will lower its thrombogenicity. Unfortunately, human EC are only
      scarcely available. Mesothelial cells (MC) have antithrombotic properties in vivo
      and can be harvested in large numbers, from the omentum. Recent work demonstrated
      that the expression of tissue factor (TF) is induced in MC after isolation and
      culture. Different culture conditions were studied to suppress TF-expression. MC
      grown in pooled human serum (HS) are procoagulant (717 +/- 119 pM factor
      Xa/min.10(5) cells). Replacing HS for fetal calf serum, precoating the surface
      with extracellular matrix and the addition of the xanthine-oxidase inhibitor
      allopurinol, inhibited TF expression by 90% (p < 0.001). Allopurinol clearly
      reduced TF-mRNA levels. TF expression on cultured MC is an in-vitro effect due to
      culture conditions and the formation of oxygen free radicals. By reducing TF
      expression by 90%, we have established conditions in which MC are a good
      alternative for EC for seeding on synthetic grafts.

PMID- 8560420
TI  - Factor VIIa in patients with C1-inhibitor deficiency.
AB  - In hereditary angioedema (HAE), normal C1-inhibitor (C1-INH) is low and the
      contact system activated. Recently, the findings of a tissue factor mutant
      selectively deficient in promoting the conversion of FVII to FVIIa, but with
      retained cofactor for FVIIa, made it possible to examine reliably the pre
      existing content of FVIIa in HAE patients. This was of interest as FXIIa (mainly
      inhibited by C1-INH) is able to activate FVII directly. FVIIa in 21 remission HAE
      patients were within normal limits but nearly doubled as compared to their 23
      normal siblings (p = 0.0017). Cold promoted activation of FVII (CPA) (common clot
      assay) was displayed in plasma of all 5 untreated patients (C1-INH function <
      35%), but not in plasma of 2 patients treated prophylactically with danazol (C1
      INH function about 40%). These results suggest that there is a minute, yet
      significant activation of FVII in patients with C1-INH deficiency.

PMID- 8560421
TI  - Inhibition of thrombin by peptides containing Lysyl-alpha-keto carbonyl
      derivatives.
AB  - Several H-N-Me-D-Phe-Pro-Lysyl-alpha-keto carbonyl derivatives were shown to be
      potent thrombin inhibitors (Ki 0.2 to 27 nM). The inhibitory potencies of these
      compounds toward tissue plasminogen activator, plasmin and factor Xa were
      minimal; however, substantial cross-reactivity versus trypsin was observed (Ki
      values from 0.5 to 1500 nM). Inhibition of thrombin by alpha-keto carbonyl
      compounds appeared to occur via a one-step reversible reaction. The alpha-keto
      carbonyl inhibitors bound thrombin with a second order rate constant (k1 1-4
      microM-1s-1) that was 10-100-fold slower than that expected for a diffusion
      controlled reaction. Certain alpha-keto carbonyl inhibitors were as potent (on a
      weight basis) as hirudin when evaluated in a rat arterial thrombosis model. The
      modest oral bioavailability (10-19%) in rats demonstrated for three of the alpha
      keto carbonyl thrombin inhibitors suggests the possibility that alpha-keto amide
      containing thrombin inhibitors may have utility as orally-active antithrombotic
      agents.

PMID- 8560423
TI  - Development of an ELISA for autoantibodies to prothrombin showing their
      prevalence in patients with lupus anticoagulants.
AB  - Some lupus anticoagulants (LA) have been shown to be directed against
      phospholipid-bound prothrombin. While developing an ELISA to detect anti
      prothrombin autoantibodies in patient serum or plasma, no or very low signal was
      observed using human prothrombin immobilized on plain polystyrene plates. In
      contrast, the same LA-positive samples bound specifically to prothrombin coated
      on gamma-irradiated plates, depending on the radiation dose, in the absence of
      added calcium and phospholipid. Optimization of the assay required the addition
      of 0.1% Tween 20 to the buffers. Antibody specificity for immobilized prothrombin
      was ascertained by competition using liposome-bound prothrombin, since fluid
      phase prothrombin competed poorly. Seventy-seven of 139 patients (55.4%) with LA
      related to a variety of underlying diseases possessed anti-prothrombin antibodies
      (27 IgG, 35 IgM and 15 both isotypes), either isolated or more often associated
      with anti-beta 2 glycoprotein I (beta 2GPI) antibodies. These included 67-71% of
      the patients with systemic lupus erythematosus and related disorders, primary
      antiphospholipid antibody syndrome or drug-induced LA (autoimmune groups), but
      only 19-20% of those with infection or malignancy (p < 0.001). As previously
      shown for anti-beta 2GPI antibodies, IgG2 was the predominant IgG subclass
      reactive with prothrombin. Thus, autoimmune patients with LA have a high
      incidence of antibodies to beta 2GPI and prothrombin, the binding of which could
      similarly require high antigen density and/or exposure of cryptic epitopes
      resulting from protein interaction with an irradiated (i.e. more anionic)
      polystyrene surface.

PMID- 8560422
TI  - Orientation of the carboxy-terminal regions of fibrin gamma chain dimers
      determined from the crosslinked products formed in mixtures of fibrin, fragment
      D, and factor XIIIa.
AB  - There are two schools of thought regarding the orientation of the intermolecular
      epsilon-amino-(gamma-glutamyl) lysine isopeptide bonds formed between gamma
      chains in the D domains of assembled fibrin fibers. Some investigators believe
      that these bonds are oriented parallel to the direction of fiber growth
      (longitudinally) at the contacting ends of fibrin D domains ('DD-long'), whereas
      others believe that these bonds are oriented across the two-stranded fibril,
      between D domains in opposing strands ('DD-transverse'). To distinguish between
      these two possibilities, the structure of crosslinked products formed in mixtures
      of fibrin, plasmic fragment D, and factor XIIIa were analyzed, based upon this
      rationale: Complex formation between D fragments and a fibrin template depends
      upon the non-covalent 'D:E' interaction between each fibrin E domain and two D
      fragments ('D:fibrin:D'). If carboxy-terminal gamma chains in the D:fibrin:D
      complex become aligned in a DD-long configuration, only crosslinked fragment D
      dimers ('D-D') will result and the fibrin 'template' will not become crosslinked
      to the associated D fragments. If instead, gamma chain crosslinks form
      transversely between the D fragments and fibrin, covalently linked D-fibrin
      complexes will result. SDS-PAGE of factor XIIIa crosslinked mixtures of fibrin
      and fragment D demonstrated products of a size and subunit composition indicating
      D-fibrin and D-fibrin-D formation. Small amounts of D dimers were also formed at
      the same levels as were formed in mixtures of fragment D and factor XIIIa alone.
      Electron microscopic images of D-fibrin-D complexes prepared under physiological
      buffer conditions demonstrated that the D fragments were associated with the
      central E domain of the fibrin molecule, but that they could be dissociated from
      this non-covalent association in 2% acetic acid. These findings indicate that
      gamma chain crosslinks occur transversely in D:fibrin:D complexes and permit the
      extrapolated conclusion that gamma chain crosslinks are also positioned
      transversely in an assembled fibrin polymer.

PMID- 8560424
TI  - Biological effects of combined inactivation of plasminogen activator and
      plasminogen activator inhibitor-1 gene function in mice.
AB  - Mice with combined homozygous deficiency of tissue-type plasminogen activator (t
      PA) and urokinase-type plasminogen activator (u-PA) (T-U-), of t-PA and
      plasminogen activator inhibitor-1 (PAI-1) (T-P-), of u-PA and PAI-1 (U-P-) or of
      t-PA, u-PA, and PAI-1 (T-U-P-) were generated by inbreeding of mice with the
      respective deficiencies. Homologous recombination at the t-PA, u-PA and PAI-1
      locus was verified by Southern blot analysis of genomic tail tip DNA, and
      confirmed by measurement of antigen levels in plasma or urine. T-P- and U-P- mice
      were apparently healthy and fertile. T-U- mice showed extensive fibrin deposition
      with calcification in the liver, whereas T-U-P- mice were significantly (p <
      0.001) less affected. Spontaneous in vivo clot lysis measured 4 h after injection
      of a 125I-fibrin-labeled clot prepared from plasma of wild-type (WT) mice into
      the jugular vein, was (mean +/- SEM of n experiments) 2 +/- 1% (n = 8) for T-P-,
      49 +/- 6% (n = 9) for U-P-, 1 +/- 1% (n = 4) for T-U- and 3 +/- 3% (n = 3) for T
      U-P- mice, as compared to 32 +/- 4% (n = 10) for WT, 1 +/- 0% (n = 7) for T-, 30
      +/- 5% (n = 5) for U- and 58 +/- 10% (n = 6) for P- mice. Plasminogen-dependent
      lysis of 125I-fibrin-labeled matrix and of 3H-proline-labeled subendothelial
      matrix (mean +/- SEM; n = 4 to 6) was lower with thioglycollate-stimulated
      macrophages obtained from U-P- mice (22 +/- 7% and 5 +/- 1%, respectively), as
      compared to WT mice (57 +/- 14% and 18 +/- 5%, respectively) and T-P- mice (87 +/
      6% and 27 +/- 4%, respectively). A similar decrease was previously observed with
      U- mice, but not with T- or P- mice. Thus, the phenotype of mice with combined
      deficiency of t-PA and PAI-1 or of u-PA and PAI-1 is similar to the phenotype
      observed in mice with single deficiency of the plasminogen activator. Additional
      deletion of PAI-1 does not affect viability, fertility, macrophage function or
      thrombolytic potential of the single deficient mice. Additional deletion of PAI
      in mice with combined deficiency of t-PA and u-PA does not restore the deficient
      in vivo fibrinolytic capacity, but significantly reduces the thrombotic
      phenotype, as revealed by fewer, smaller and less calcified fibrin deposits in
      the liver.

PMID- 8560425
TI  - Magnesium modifies the responses of platelets to inhibitory agents which act via
      cAMP.
AB  - This study has investigated the interaction of raised extracellular magnesium and
      agents which act via cAMP with respect to inhibition of platelet aggregation and
      effects on platelet cAMP accumulation. Iloprost (3 ng/ml) and PGD2 (0.2
      microgram/ml) each caused time dependent increases in platelet cAMP which were
      significantly greater in the presence of 3 mM added MgSO4 (p < 0.01). Addition of
      ADP (5 microM) resulted in a fall in cAMP which remained higher in the presence
      of MgSO4 (p < 0.01). Forskolin (5 micrograms/ml) and DN9693 (100 microM) also
      caused increments in platelet cAMP but these responses were not influenced by
      added MgSO4. Addition of ADP resulted in a further increase in cAMP which was
      augmented by MgSO4 (p < 0.03). This increase was abolished by adenosine deaminase
      (1.2 U/ml). These experiments show that MgSO4 can modify the cAMP responses
      produced by iloprost and PGD2 and by forskolin and DN9693 when ADP is present. It
      appears that as well as inhibiting, ADP can also stimulate cAMP production under
      certain experimental conditions. This appears to be due to breakdown of ADP to
      adenosine.

PMID- 8560426
TI  - Targeting of porcine pancreatic phospholipase A2 to human platelets: introduction
      of an RGD sequence by genetic engineering.
AB  - The possibility to induce specific disruption of activated platelets by binding
      of porcine pancreatic phospholipase A2 (PLA2) was tested by constructing a set of
      PLA2-mutants containing an Arg-Gly-Asp (RGD) sequence. One mutant was made with
      RGD as part of a surface-exposed loop (RGDloop). Four mutants were made with RGD
      as part of a C-terminal extension: one with RGD directly coupled to the C
      terminus (RGDc) and three mutants (CRSx) with x= 22, 42 and 82 hydrophylic non
      charged amino acids between RGD and the enzyme. All mutants retained 20-80%
      activity of native PLA2 and showed little binding to resting platelets. The
      binding of the native enzyme and RGDloop was not increased following stimulation.
      In contrast, the mutants RGDc and CRSx showed stimulation-dependent binding to
      the platelet receptor GPIIb/IIIa, since GRGDS-peptide and a monoclonal antibody
      against the complex interfered with binding. In alpha-thrombin-stimulated
      platelets, CRS42 and CRS82 induced about 5% hydrolysis of [3H]-arachidonic acid
      labeled phospholipids. Stimulation with a combination of alpha-thrombin and
      collagen (known to expose phosphatidylserine) increased hydrolysis to 11%.
      Despite the membrane disruption, the cells did not leak lactate dehydrogenase. We
      conclude that PLA2 can be targeted to activated platelets by introducing RGD in a
      C-terminal extension with a minimum distance (42 amino acids) between RGD and the
      enzyme. However, more hydrolytic activity is required to eliminate activated
      platelets among a suspension of resting platelets and other blood cells.

PMID- 8560427
TI  - Ultrastructural detection of surface exposed phosphatidylserine on activated
      blood platelets.
AB  - Phosphatidylserine (PS) is normally restricted to the inner leaflet of the plasma
      membrane of cells (including blood platelets). Upon cell activation PS may become
      exposed to the outer surface of the cell. Cell membranes with surface exposed PS
      at the outside form a catalytic surface for coagulation reactions. When platelets
      are activated with ionophore or with thrombin in combination with thapsigargin,
      calcium induced scrambling of phospholipids takes place, resulting in PS
      exposure. Concomitant with PS exposition structural changes take place. On
      resting and activated platelets we combined the immunocytochemical detection of
      surface exposed PS with (ultra)structural information. Blood platelets were
      activated in the presence of annexin V, a protein which binds to PS in the
      presence of Ca2+. Annexin V was found to bind to lipid bilayers containing more
      than 5 mole % PS as estimated by binding of fluorescent-labelled annexin V to
      liposomes with varying PS concentrations. After vitrification, freeze
      substitution and embedding of the platelets, annexin V was located on ultra thin
      sections, as detected by an anti-annexin V antibody and gold labelled protein A.
      Upon activation, the platelets show two different forms; irregular platelets with
      unchanged cytoplasm and round cells with apparently diluted cytoplasm. Activation
      with ionophore initially resulted in both forms, but after ten minutes only round
      platelets with diluted cytoplasm were observed. Both forms of these platelets as
      well as the microvesicles were found to be annexin V positive. However upon
      activation with thrombin in combination with thapsigargin, only the round cells
      with diluted cytoplasm and microvesicles were annexin V positive, whereas
      platelets with unchanged cytoplasm, even when microvesicles are present, are
      negative for annexin V.

PMID- 8560428
TI  - Inhibition of platelet aggregation by an SLE-derived human hybridoma autoantibody
      against an activation-dependent antigen.
AB  - Anti-platelet autoantibodies may be responsible for hematological complications
      in patients with systemic lupus erythematosus (SLE), but the mechanisms by which
      these antibodies cause abnormal hemostasis remain unknown. In the present study,
      using fluorescence activated cell sorter (FACS) analysis, we demonstrate that an
      SLE-derived human hybridoma autoantibody, 9604, recognizes a surface antigen
      expressed on platelets activated by ADP, calcium ionophore A23187, or phorbol
      myristate acetate (PMA), showing saturation with approximately 2,000 antibody
      molecules bound per platelet and a Kd of 41 nM. The binding of 9604 to activated
      platelets was significantly inhibited by EDTA, indicating partial dependence on
      divalent cations. It did not appear to be dependent on platelet secretion, nor
      did it directly affect alpha-granule or dense granule secretion. The protein
      antigen responsible for the binding of 9604 to activated platelets was
      characterized by Western blot and immunoprecipitation and shown to have a native
      molecular weight (M. W.) of greater than 400,000, with a 32,000 M. W. subunit (p
      32). Antibody 9604 had little or no effect on the shape change and the initial
      rate of primary aggregation of normal platelets. In contrast, 9604 inhibited
      secondary aggregation of stirred platelet suspensions (IC50 < or = 1 nM)
      following activation by ADP, thromboxane A2 mimetic U46619, or calcium ionophore
      A23187, but not PMA or thrombin. The inhibition of large platelet aggregate
      formation (secondary aggregation), with a major shift to smaller microaggregates
      and singlets, was confirmed by direct particle count and sizing studies. The
      functional inhibition of platelet aggregation by an SLE-derived human hybridoma
      autoantibody in vitro suggests one potential mechanism that may play a role in
      the hemostatic disorders found in SLE.

PMID- 8560429
TI  - Effects of heparin and hirudin on thrombin generation and platelet aggregation
      after intrinsic activation of platelet rich plasma.
AB  - The effects of unfractionated heparin (UH) and recombinant hirudin (rH) on
      prothrombin activation, free thrombin generation, and platelet aggregation
      induced by endogenously generated thrombin after intrinsic activation of platelet
      rich plasma were compared. Free thrombin generation and platelet aggregation were
      assessed simultaneously by delaying fibrinogen polymerisation with GPRP. UH more
      effectively inhibited prothrombin activation and free thrombin generation than
      rH. Increasing concentrations of rH had hardly any effect on the peak amount of
      free thrombin, while in the presence of 400 nM UH only traces of free thrombin
      were detected. Comparison of TAT and THC (thrombin-hirudin complex) generated
      until the onset of platelet aggregation on a molar basis showed that much more
      thrombin was inactivated in the presence of rH than in plasma containing UH. The
      explosive generation of free thrombin in hirudinized plasmas was accompanied by a
      markedly steeper aggregation curve as compared to heparinized plasmas. The
      generation of thromboxane B2 was markedly delayed in the presence of UH but not
      influenced in the presence of rH. Our results suggest that UH is more effective
      than rH in inhibiting prothrombin activation after intrinsic activation of
      platelet rich plasma, while rH prevents clotting more by direct inactivation of
      already generated thrombin. The inability of even high concentrations of rH to
      prevent the explosive generation of free thrombin might contribute to the
      observed inefficiency of rH to inhibit platelet aggregation.

PMID- 8560430
TI  - Minimum fragments of the heparin molecule able to produce the accumulation and
      change of the sulfation pattern of an antithrombotic heparan sulfate from
      endothelial cells.
AB  - Heparin and low molecular weight heparins stimulate two to three fold the
      accumulation of an antithrombotic heparan sulfate secreted by endothelial cells
      in culture. This led us to search for the minimum structural requirements of the
      heparin molecule able to elicit the enhancement of the heparan sulfate. Fragments
      were prepared from heparin by degradation with bacterial heparinase and
      heparitinases. A heparin pentasulfated tetrasaccharide was shown to be the
      minimum structural sequence able to enhance two to three fold the secretion of
      heparan sulfate by endothelial cells. The stimulation is specific for the
      endothelial cell, is concentration dependent and the effect is already noticed
      after one hour of exposure of the cells to heparin and the tetrasaccharide.
      Degradation of the [35S]-heparan sulfate synthesized in the presence of heparin
      or the tetrasaccharide has shown a higher degree of sulfation of its iduronic
      acid residues.

PMID- 8560431
TI  - Oxidized LDL and reduction of the antiaggregating activity of nitric oxide
      derived from endothelial cells.
AB  - Oxidized LDL has been observed to induce abnormalities in endothelial function
      which may be relevant for the progression of atherosclerotic lesions. We studied
      in vitro the possible effects of oxidized LDL on the antiaggregating activity of
      endothelial cells, which is dependent on release of prostacyclin and nitric
      oxide. We used an experimental model in which cultured human endothelial cells
      were placed in the aggregometer in contact with human platelets, after blockade
      of cyclo-oxygenase by adding acetylsalicylic acid. In this way the antiaggregant
      effect of endothelial cells was dependent on the release of nitric oxide alone;
      prevention of antiaggregant activity by preincubation of endothelial cells with
      300 microM L-NG-mono-methylarginine confirmed this. When this system was used,
      endothelial cells (2-7.5 x 10(5)/ml) almost completely inhibited thrombin-induced
      (0.02-0.08 U/ml) platelet aggregation (2 x 10(8) platelets/ml), measured
      according to Born (11.1% +/- 8.5 vs 68.6% +/- 12.6, M +/- SD). This
      antiaggregating activity was reduced when slightly oxidized LDL 100 micrograms/ml
      (35.2% +/- 14.9, p < 0.001), but not native LDL 100 micrograms/ml (7.5% +/- 7.6),
      was added immediately before aggregation was induced. Incubation of endothelial
      cells with oxidized LDL 100 micrograms/ml for 1 h did not affect the
      antiaggregating capacity, unless oxidized LDL was present during aggregation
      (18.3% +/- 10.2 vs 35.8% +/- 9.6, p < 0.02). No significant direct effect of
      either oxidized or native LDL on stimulated platelet aggregation was observed.
      Our results indicate that slightly oxidized LDL can reduce the antiaggregating
      properties of the endothelium, probably by interaction with NO rather than
      through inhibition of its synthesis.

PMID- 8560432
TI  - Estimation of the carbohydrate moiety of von Willebrand factor in the plasma of
      patients with subtypes 2a and 2b of von Willebrand disease.
AB  - Von Willebrand disease (vWD) results from quantitative (types 1 and 3) or
      qualitative (type 2) deficiency of von Willebrand factor (vWF). This glycoprotein
      present in plasma is involved in platelet adhesion at the site of vascular injury
      and serves as the carrier of antihaemophilic A factor (FVIII). Whereas recent
      studies have identified mutations in patients suffering from type 2 vWD, the
      integrity of the carbohydrate moiety of vWF in these patients is still matter of
      debate. In order to analyse in the plasma milieu the carbohydrate content of
      plasma vWF from various well-characterized type 2 vWD patients, we developed a
      colorimetric assay in microtiter plate based on the use of peroxidase-conjugated
      lectins specific for either alpha 2-6 sialic acid or beta 1-4 galactose. Removal
      of sialic acid from purified plasma vWF induced significant changes in the
      reactivity of both lectins. The analysis of various normal plasmas showed no
      influence of the blood groups and allowed us to compare various vWD patients. The
      reactivity of lectins for plasma vWFs from two type 2A and six type 2B vWD
      patients harbouring different mutations was not statistically different from that
      of a pool of normal plasmas. We conclude that the alpha 2-6 sialic acid and beta
      1-4 galactose content of plasma vWF is not altered in these patients affected
      with types 2A and 2B vWD.

PMID- 8560433
TI  - Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the
      Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific
      and Standardisation Committee of the ISTH.

PMID- 8560434
TI  - In vivo recovery of factor VIII following transfusion: a survey of recent data
      and publications to assess the influence of standards used for potency
      assignment. On behalf of the Subcommittee on Factor VIII and IX of the Scientific
      and Standardization Committee of the ISTH.
AB  - In the therapy of factor VIII deficiency, experience has taught the value of
      achieving a target level of plasma coagulation factor VIII. There is a consensus
      that an empirical value of 2 iu/dl/iu/kg may be used to estimate recovery, and
      hence plasma levels, of factor VIII. This may be influenced by the methods used
      to assign label potency to the products and for assessment of patient post
      infusion plasmas. To assess a possible influence of the standard used to assign
      product potency on in vivo recovery, a survey was undertaken of recent in vivo
      recovery studies. Analysis of submitted data, in combination with published
      studies over the last ten years, revealed a significant influence of the standard
      used to assign potency to products on the measured in vivo recovery. Furthermore,
      from limited data the potency determined in post-infusion patient plasmas was
      found not to be influenced by the use of one-stage or chromogenic assay methods.

PMID- 8560435
TI  - Resistance to activated protein C--diagnostic strategy in a laboratory of
      haemostasis.

PMID- 8560436
TI  - Lowered APC-sensitivity ratio related to increased factor VIII-clotting activity.

PMID- 8560437
TI  - Thrombophilia in a child with CDG-syndrome type I.

PMID- 8560439
TI  - Alu-repeat polymorphism in the tissue-type plasminogen activator (tPA) gene does
      not affect basal endothelial tPA synthesis.

PMID- 8560438
TI  - Relation between plasma PAI activity and adipsin levels.

PMID- 8560440
TI  - Five-year follow-up of human anti-mouse antibody in multitransfused HIV negative
      haemophilics treated with a monoclonal purified plasma derived factor VIII
      concentrate.

PMID- 8560441
TI  - Complement activation and tissue factor expression on the feto-placental
      allograft.

PMID- 8560442
TI  - Differentiation of beef and pig mucosal heparins by NMR spectroscopy.

PMID- 8560443
TI  - Does albumin affect clotting of fibrinogen with thrombin?

PMID- 8560444
TI  - Increased incidence of cardiovascular attacks in the epicenter just after the
      Hanshin-Awaji earthquake.

PMID- 8560445
TI  - Sulfated polysaccharide anticoagulants suppress natural killer cell activity in
      vitro.
AB  - In contrast to the well studied anticoagulant activity of sulfated
      polysaccharides (SPS), little is known about their influence on immune competent
      cells. Using two naturally derived SPSs (unfractionated heparin and low molecular
      weight heparin), one semi-synthetic SPS (pentosanpolysulfate), and one synthetic
      SPS (lactobionic acid) as well as the polypeptide hirudin we investigated the
      effect of these drugs on natural killer cell activity in vitro. We demonstrate
      that all SPSs tested significantly suppress the activity of natural killer cells
      at clinically relevant dosages. At all concentrations and at all effector:target
      ratios tested pentosanpolysulfate was the most potent natural killer cell
      inhibitor. In contrast, hirudin had no effect on natural killer cell function.
      Furthermore, scanning electron microscopy revealed that reduced natural killer
      cell activity is paralleled by decreased lymphocyte cell size and altered cell
      surface structures. Our results indicate that defined therapeutically applied
      SPSs can interfere with the tumor cell killing process.

PMID- 8560446
TI  - Complete generic and extensive fine-specificity typing of the HLA-B locus by the
      PCR-SSOP method.
AB  - This study describes sequence specific oligonucleotide probe (SSOP) typing of
      hypervariable regions in exons 2 and 3 of HLA-B locus genes. A single HLA-B
      specific PCR-product spanning from bp 84 in exon 2 to bp 241 in exon 3 was used
      for dot blot hybridization to forty-seven chemiluminescent labeled
      oligonucleotide probes. Thirty-one of these probes were derived from four
      hypervariability zones in exon 3 of HLA-B genes and covered most known sequence
      polymorphisms within these regions. In addition, sixteen probes derived from
      polymorphic regions in exon 2 were used to discriminate alleles not unequivocally
      characterized by the exon 3 based probes. This SSOP panel gave rise to eighty-six
      distinct hybridization patterns that could be used to unequivocally define all
      WHO-designated serological HLA-B specificities except for HLA-B54 in all homo-
      and heterozygous combinations. Furthermore, sixty-six out of ninety-seven
      molecularly defined HLA-B subtypes were characterized by unique hybridization
      patterns in all homozygous and most (possibly all) heterozygous combinations. The
      reproducibility of these results was confirmed by analysis of forty-four Workshop
      reference cell lines and of seventy-eight randomly chosen samples (one-hundred
      forty-seven alleles) from unrelated individuals serologically typed in the
      laboratory. For sixty-five samples (one-hundred-thirty-three alleles), molecular
      typing confirmed the results obtained by serology and allowed molecular subtype
      assignment for ninety-one alleles tested. A serologically blank allele could be
      defined by molecular analysis in three cases. The method presented here for
      molecular typing of the HLA-B locus can be used as an alternative to biochemical
      methods such as one-dimensional isoelectric focusing for assignment of
      serologically cross-reacting HLA-B molecules as well as for subtype
      characterization of a large variety of HLA-B alleles.

PMID- 8560447
TI  - Molecular analysis of HLA class II polymorphism in Croatians.
AB  - HLA-class II polymorphisms have been studied in a population of 141 unrelated
      healthy Croatians using PCR amplification, followed by non-radioactive
      oligonucleotide hybridization. Thirty one DRB1, 8 DQA1, 13 DQB1 and 16 DPB1
      alleles were found in the tested population. DRB1*1601, 0701, 1501, 0101 and 1104
      are the most frequent alleles at the DRB1 locus. At the DQA1 locus two alleles
      predominate: DQA1*0501 and 0102, while the most frequent DQB1 allele is *0301.
      Analysis of HLA-DPB1 polymorphism showed that, as in other Europeans, DPB1*0401
      is the most frequent allele. Four different two locus haplotypic associations
      (DRB1-DRB3, DRB1-DRB5, DRB1-DQB1 and DQA1-DQB1) as well as three locus DRB1-DQA1
      DQB1 haplotypic associations were assigned on the basis of known linkage
      disequilibria. Several unusual two-locus associations have been observed:
      DRB1*0301-DRB3*0202, DRB1*1501-DRB5*02, DRB1*1601-DRB5*0101, DRB1*1502-DRB5*0101,
      DQA1*0103-DQB1*0503 and DQA1*0501-DQB1*0302. Among 236 examined DRB1-DQA1-DQB1
      haplotypic combinations, the most frequent was DRB1*1601-DQA1*0102-DQB1*0502 that
      was found with statistically significant higher frequency than in other
      Europeans. Twenty-eight distinct probable haplotypes were observed just once,
      suggesting that the main characteristic of Croatian population is great
      heterogeneity of haplotypes. This study will serve as a reference for further
      anthropology studies, HLA and disease associations studies and for
      donor/recipient matching in organ and bone marrow transplantation.

PMID- 8560448
TI  - DQCAR microsatellite polymorphisms in three selected HLA class II-associated
      diseases.
AB  - DQCAR is a very polymorphic CA repeat microsatellite located between the HLA DQA1
      and DQB1 gene. Previous studies have shown that specific DQCAR alleles are in
      tight linkage disequilibrium with known HLA DR-DQ haplotypes. Of special interest
      was the fact that haplotypes containing long CA repeat alleles (DQCAR > 111) were
      generally more polymorphic within and across ethnic groups. In these latter
      cases, several DQCAR alleles were found even in haplotypes containing the same
      flanking DQA1 and DQB1 alleles. In this work, three HLA class II associated
      diseases were studied using the DQCAR microsatellite. The aim of this study was
      to test if DQCAR typing could distinguish haplotypes with the same DRB1, DQA1 and
      DQB1 alleles in control and affected individuals. To do so, patients with
      selected HLA DR-DQ susceptibility haplotypes were compared with HLA DR and DQ
      matched controls. This included: Norwegian subjects with Celiac disease and the
      HLA DRB1*0301, DQA1*05011, DQB1*02 haplotype; Japanese subjects with Type 1
      (insulin-dependent) Diabetes Mellitus and the HLA DRB1*0405, DQA1*0302, DQB1*0401
      haplotype; and French patients with corticosensitive Idiopathic Nephrotic
      Syndrome and the HLA DRB1*0701, DQA1*0201, DQB1*0202 haplotype. These specific
      haplotypes were selected from our earlier work to include one haplotype bearing a
      short DQCAR allele (celiac disease and DR3,DQ2-DQCAR99) and two haplotypes
      bearing long DQCAR alleles (Diabetes Mellitus and DR4,DQ4-DQCAR 113 or 115
      Idiopathic Nephrotic syndrome and DR7,DQ2-DQCAR 111-121). Additional DQCAR
      diversity was found in both control and patients bearing haplotypes with long CA
      repeat alleles. The results indicate that DQCAR typing did not improve
      specificity in combination with high resolution DNA HLA typing as a marker for
      these three disorders.

PMID- 8560449
TI  - Characterization of two human IgM monoclonal antibodies reactive with HLA-B27.
AB  - We describe here the generation and characterization of two human monoclonal IgM
      antibodies (UL-4F11 and UL-F6) reactive with HLA-B27. The monoclonal antibody
      (mAb) UL-4F11 is cytotoxic for peripheral mononuclear cells and, therefore,
      useful as typing reagent for HLA-B27 and HLA-B38. Protein chemistry showed that
      the mAb UL-4F11 precipitates HLA-B27 molecules. Epitope mapping analysis suggests
      that the amino acids 45, 67, 82 and 83 (alpha-1 domain) of the HLA-B27 sequence
      are necessary for mAb UL-4F11 reactivity. The mAb UL-F6 is suitable for
      complement dependent lysis of lymphoblastoid cell lines and stimulated peripheral
      blood mononuclear cells with HLA-B27 (B*2701, B*2702, B*2703, B*2705, B*2707),
      B13, B40 (60,61), B47 and B48 specificities. Its reactivity indicates that the
      amino acid valine in position 152 and glutamic acid in position 163 of the alpha
      2 domain are crucial for the binding epitope.

PMID- 8560450
TI  - HLA phenotypes and severe Rh(D) immunization.
AB  - Blood samples from 24 Rh(D) immunized women were analyzed for antibody titers and
      quantification of anti-D. The HLA-DR and -DQ polymorphisms were identified as
      RFLP. In 11 women with titers 16-256 the HLA-DQB1 allele *0201 was found in 18%,
      i e as in a reference population. In 13 women with titers > or = 512 the HLA-DQB1
      allele *0201 was found in 85% indicating a correlation between severe Rh(D)
      immunization with high titers/quantification values and the DQB1 allele *0201. In
      this group the fetus was severely affected by the immunization and treatment
      during pregnancy was frequently needed. HLA phenotyping of women known to have
      anti-D antibodies early in pregnancy seems to be an effective way to assess the
      probability of severe hemolytic disease of the newborn.

PMID- 8560451
TI  - Expression of an unusual Bw4 epitope by a subtype of HLA-B8 [B*0802].
AB  - The primary structure of a variant HLA-B8 antigen has been determined by cDNA
      cloning and sequencing. The variant, B*0802 differs, from the common B*0801
      subtype at positions 77-83 of the alpha 1 helix that determine the Bw4 and Bw6
      public epitopes. Whereas B*0801 has the common Bw6 motif, B*0802 has the Bw4
      motif found in B*13 and B*44 allotypes. Serological analysis of B cell lines
      expressing B*0802 and of a B*0802 transfectant made with the HLA-A,B negative
      cell line 721.221 shows that B*0802 reacts with Bw4-specific antibodies, but at a
      level much lower than expected for Bw4 positive HLA-B allotypes.

PMID- 8560452
TI  - A novel HLA-A30 allele (A*3004) identified by single-strand conformation
      polymorphism analysis and confirmed by solid-phase sequencing.

PMID- 8560453
TI  - A cytotoxic human monoclonal antibody that can discriminate HLA-A*3002 from HLA
      A*3001 subtypes.

PMID- 8560454
TI  - Homogeneity of allelic sequence for serological variants of HLA-B53.

PMID- 8560455
TI  - The multiple sclerosis- and narcolepsy-associated HLA class II haplotype includes
      the DRB5*0101 allele.

PMID- 8560456
TI  - A novel DRB1 allele (HLA-DRB1*1318) featuring a DR8-associated sequence motif on
      a DR52 haplotype.

PMID- 8560457
TI  - A new HLA-DR8 subtype showing unusual serological reaction and the confirmatory
      sequence of DRB1*0809.

PMID- 8560458
TI  - A novel HLA-DR allele, DRB1*1419.

PMID- 8560459
TI  - Ambiguous DPB1 allele combinations resolved by direct sequencing of selectively
      amplified alleles.

PMID- 8560460
TI  - Nomenclature for factors of the HLA system, update July 1995.

PMID- 8560461
TI  - Determination of aflatoxin B1 biotransformation and binding to hepatic
      macromolecules in human precision liver slices.
AB  - Although epidemiological studies suggest that aflatoxin B1 (AFB1) is a human
      carcinogen, at least in the presence of hepatitis B virus infection, animal
      studies have demonstrated large differences in species sensitivity to AFB1, and
      the sensitivity of humans relative to experimental animals remains unclear. The
      purpose of this study was to determine the profile of AFB1 metabolism and the
      extent of AFB1 binding to cell macromolecules in human liver slices under
      experimental conditions that would allow direct comparison to similar endpoints
      in the rat, a species sensitive to the carcinogenic actions of AFB1. Liver slices
      were prepared from three individual human liver samples with a Krumdieck tissue
      slicer and incubated with 0.5 microM [3H]AFB1 for 2 hr. Significant
      interindividual variations were observed in the rates of oxidative metabolite
      formation and in specific binding to cell macromolecules. The rates of oxidative
      metabolism of AFB1 to AFQ1, AFP1, and AFM1 in the three human liver samples were
      similar to those previously observed in rat liver slices. AFB1-GSH conjugate
      formation was not detected in any of the human liver samples, and yet specific
      binding of AFB1 to cell macromolecules was considerably lower in the human liver
      slices relative to that in rat liver slices. AFB1-DNA binding levels ranged from
      3 to 26% of control rat and AFB1-RNA binding levels ranged from 25 to 49% of
      control rat. The AFB1-protein binding level in the one human sample measured was
      20% of that observed for control rat. While these results suggest that humans do
      not form as much AFBO as the rat, they are also consistent with the hypothesis
      that humans do not possess GST isozyme(s) with high specific activity toward
      AFBO. Significant individual differences in AFB1 metabolism and binding between
      humans suggest the presence of genetic and/or environmental factors that may
      confer large variability in susceptibility to AFB1.

PMID- 8560462
TI  - Mg2+ antagonism on Ni(2+)-induced changes in microtubule assembly and cellular
      thiol homeostasis.
AB  - As an essential metal for cell metabolism, Mg2+ is known to exert antagonism on
      Ni2+ genotoxic and other effects. This study examined the influence of Mg2+ on
      Ni(2+)-induced changes in microtubule (MT) assembly in vitro, cytoplasmic MT
      organization, cellular glutathione (GSH), and cytoskeletal and cytosolic protein
      sulfhydryls (PSH). As determined by a turbidity assay at 27 degrees C, Ni2+
      enhanced the in vitro MT assembly in a Pipes buffer by shortening the initial lag
      (nucleation phase) and increasing the rate of polymerization with a higher final
      plateau. However, presence of 1 mM exogenous MgCl2 abolished the Ni2+ enhancing
      effect. Exposure of 3T3 cells to 2 mM NiCl2 for 20 hr resulted in perinuclear
      bundling of MTs and decreases in cytoskeletal and cytosolic PSH and cellular GSH
      levels. However, coincubation of cells with MgCl2 (1.25-20 mM) added to the
      culture medium markedly diminished the Ni2+ injury to MT organization. Under
      these conditions the Ni2+ interference with PSH was blocked such that both the
      cytoskeletal and cytosolic PSH levels returned to the range of control cells
      without metal treatment. Treatment of cells with Mg2+ (1.25-5 mM) for 20 hr
      slightly increased, while with higher Mg2+ doses (> 10 mM) decreased, cellular
      GSH content. Importantly, in Ni(2+)-treated cultures, addition of Mg2+ (1.25-10
      mM) elevated GSH levels to > or = 200% of that in cells treated with Ni2+ alone.
      Furthermore, these Ni2+ and Mg2+ (1.25-10 mM) treated cells actually maintained
      GSH levels which were essentially unchanged from the basal level of control cells
      with no metal treatment. Although Mg2+ replacement of Ni2+ bound to MT proteins
      could be an important mechanism, cellular GSH may also be a critical factor in
      Mg2+ antagonism on Ni(2+)-enhanced MT assembly in view of the essential role of
      tubulin PSH in modulating MT assembly and, in turn, the GSH modulation of PSH.

PMID- 8560463
TI  - Neonatal polychlorinated biphenyl treatment increases adult testis size and sperm
      production in the rat.
AB  - Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants which
      decrease serum thyroxine (T4) concentrations. We have previously demonstrated
      that neonatal hypothyroidism in the rat increases Sertoli cell numbers, adult
      testis weight, and daily sperm production (DSP). The aim of this study was to
      determine if neonatal PCB treatment increases adult testis weight and DSP.
      Treated rats received either Aroclor 1242 or 1254 (0.4-3.2 mg/day), from birth to
      Day 25 by daily injection; some treated litters also received T4 replacement.
      Controls received vehicle alone. Tritiated thymidine autoradiography was used to
      assess Sertoli cell proliferation in 15-day control and Aroclor-treated rats.
      Serum T4 was measured at 25, 45, and 135 days of age, and serum testosterone,
      testis weight, DSP, and testicular histology were examined at 135 days. Both
      Aroclor 1242 and 1254 suppressed serum T4 concentrations; Aroclor 1254 was more
      potent and long lasting. Testis weight was increased 22 and 13% in rats that
      received the 1.6 and 3.2 mg/day Aroclor 1242 doses, respectively, while the 0.4
      mg/day dose did not produce significant increases. Aroclor 1254 produced
      significant increases in testis weight of 13 and 23% at the 0.4 and 1.6 mg/day
      doses, respectively. The 1.6 mg/day Aroclor 1242 and the 0.4 and 1.6 mg/day
      Aroclor 1254 doses increased DSP by 27, 11, and 42%, respectively; other
      treatments did not produce significant increases. At 15 days of age, Sertoli cell
      proliferation was greater in treated rats than in controls. T4 replacement
      decreased or eliminated the increased testis weight and DSP seen in Aroclor
      treated rats. The highest dose of Aroclor 1242 and both doses of Aroclor 1254
      decreased adult body weight, while other treatments did not. These results
      indicate that neonatal PCB treatment increases adult testis weight and DSP in
      rats. PCBs produce this effect primarily by inducing hypothyroidism, which leads
      to increased Sertoli cell proliferation, testis weight, and DSP. Thus PCBs,
      despite inhibitory effects on adult reproductive organs, can paradoxically
      stimulate increases in adult testis weight and DSP when administered neonatally.
      These data emphasize the pleiotropic nature of PCB effects and the susceptibility
      of the developing reproductive system to environmental factors.

PMID- 8560464
TI  - Inhibition of rat brain phosphatidylinositol-specific phospholipase C by
      aluminum: regional differences, interactions with aluminum salts, and mechanisms.
AB  - We have shown previously that aluminum chloride (AlCl3, 10-500 microM) inhibits
      hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by
      phosphatidylinositol-specific phospholipase C (PI-PLC) in a concentration
      dependent manner. In the present study, we characterize further the effects of
      aluminum on PI-PLC. A comparison of different brain regions and liver revealed
      varying basal PI-PLC specific activities, as well as differential susceptibility
      to inhibition by 100 microM AlCl3. The hippocampus had the highest specific
      activity of PI-PLC, followed by striatum, frontal cortex, cerebellum, and liver.
      PI-PLC inhibition by 100 microM AlCl3 was greatest in the liver, followed by
      cerebellum, hippocampus, cortex, and striatum. Moreover, 100 microM AlCl3 or
      aluminum lactate (Al (lac)) were similarly effective at inhibiting PI-PLC
      activity in rat cortical tissue. Addition of AlCl3 (100 microM) decreased PI-PLC
      activity at CaCl2 concentrations ranging from 0 to 2 mM; however, AlCl3 did not
      affect the shape of the calcium concentration curve, suggesting that aluminum
      does not inhibit PI-PLC activity by interference with the cofactor, calcium.
      AlCl3 (100 microM) did inhibit rat cortical PI-PLC hydrolysis of PIP2 in a
      competitive manner. These results demonstrate some regional/tissue differences in
      PI-PLC activity and its sensitivity to aluminum, and effects of AlCl3 and Al(lac)
      consistent with the effects previously noted in PI turnover in brain slices.
      Furthermore, our results suggest that competitive inhibition of PLC-mediated PIP2
      hydrolysis by aluminum is a potential mechanism by which aluminum may cause the
      disruptions phosphoinositide signaling which have been reported following in vivo
      and in vitro exposure.

PMID- 8560465
TI  - A tissue composition-based algorithm for predicting tissue:air partition
      coefficients of organic chemicals.
AB  - The objectives of the present study were (i) to develop an algorithm for
      predicting the tissue:air partition coefficients (PCs) of volatile organic
      chemicals (VOCs) and (ii) to apply this algorithm to predict the rat tissue:air
      PCs of 45 VOCs. The approach consisted of estimating the tissue:air PCs by
      dividing the tissue solubility of chemicals by their saturable vapor
      concentrations. The tissue solubility of chemicals was calculated as the sum
      total of their solubility in neutral lipid, phospholipid, and water fractions of
      tissues. The rat liver:air, muscle:air, and adipose tissue:air PCs predicted
      using this algorithm compared well with literature data available for several
      ketones, alcohols, acetate esters, alkanes, haloalkanes, aromatic hydrocarbons,
      and diethyl ether. The average ratios between the predicted and experimental
      values of the tissue:air PC values were 0.94 (liver), 0.93 (muscle), and 1.10
      (adipose tissue). The mechanistic algorithm developed in the present study should
      be useful for predicting tissue:air PCs of VOCs and for verifying the current
      default assumption of considering tissue:air PCs to be species-invariant.

PMID- 8560466
TI  - A mechanistic algorithm for predicting blood:air partition coefficients of
      organic chemicals with the consideration of reversible binding in hemoglobin.
AB  - The objectives of the present study were (i) to develop a mechanistic algorithm
      for predicting blood:air partition coefficients (PCs) of volatile organic
      chemicals (VOCs), and (ii) to apply this algorithm to predict the rat blood:air
      PCs of several VOCs. The approach consisted initially of developing an algorithm
      to predict the blood:air PCs of VOCs solely based on the solubility phenomenon
      and then of extending the algorithm to include protein binding. The algorithm
      based on solubility phenomenon predicted blood:air PCs by dividing the estimated
      solubility of chemicals in blood by their saturable vapor concentrations at 37
      degrees C. The rat blood:air PCs predicted using this algorithm were in close
      agreement with the experimental values for relatively hydrophilic VOCs such as
      ketones, alcohols, acetate esters, and diethyl ether (with an average ratio of
      0.80 between predicted and experimental values), whereas there was a marked
      discrepancy in the case of relatively lipophilic VOCs such as alkanes,
      haloalkanes, and aromatic hydrocarbons (with an average ratio of 0.21 between
      predicted and experimental values). This discrepancy was hypothesized to be due
      to the occurrence of reversible binding of these substances in rat hemoglobin
      based on literature evidence of the existence of hydrophobic holes (or "xenon
      binding" pockets). The association constants (Ka) for the presumed reversible
      hemoglobin binding of several alkanes, haloalkanes, and aromatic hydrocarbons
      were estimated from the difference between chemical concentration in rat
      erythrocytes predicted by the solubility-based algorithm and that deduced from
      the previously published experimental blood:air PCs for these chemicals (which
      presumably included contribution of hemoglobin binding in addition to "true"
      solubility). The Ka values estimated in this manner ranged from 504 to 4725 M-1
      for the chemicals investigated in the present study. The a priori predictions of
      the percentage of several VOCs (diethyl ether, methyl isobutyl ketone, n-hexane,
      toluene, and chloroform) in rat erythrocytes obtained with the algorithm using
      these Ka estimates corresponded well with previously published experimental data.
      The mechanistic algorithm developed in the present study should be useful for
      predicting the "apparent" blood:air PCs of VOCs regardless of exposure
      concentrations, by accounting for the relative contributions of both the true
      chemical solubility and reversible hemoglobin binding.

PMID- 8560467
TI  - L-2-chloropropionic acid-induced neurotoxicity is prevented by MK-801: possible
      role of NMDA receptors in the neuropathology.
AB  - We have demonstrated that following a single oral dose of L-2-chloropropionic
      acid (L-CPA) to rats (750 mg/kg; pH 7) there was a marked and widespread loss of
      granule cells in the cerebellum as assessed by neuropathology by 48 hr. There
      also appeared to be limited damage to Purkinje cells, whereas stellate, Golgi,
      and basket cells were not affected by L-CPA administration. The L-CPA-mediated
      cerebellar neuropathology was accompanied by a significant increase in the
      cerebellar water content and sodium concentration, 48 hr following L-CPA
      administration, suggesting an edematous reaction. After 36 hr, the animals
      displayed marked locomotor dysfunction and had to be terminated at 54 hr due to
      marked weight loss. We did not observe any neuropathology in forebrain regions
      nor was the water content in the forebrain significantly different from controls
      in animals which had been treated with L-CPA. Cerebellar aspartate concentrations
      were reduced 48 hr following L-CPA administration becoming marked at 54 hr and
      accompanied by a significant reduction in cerebellar glutamate concentrations.
      The density of N-methyl-D-aspartate (NMDA) receptors in the granular layer of the
      cerebellar cortex was also significantly reduced at 48 and 54 hr following L-CPA
      administration. Prior administration of MK-801 (dizocilpine) (5 mg/kg/i.p.), an
      irreversible NMDA receptor antagonist, 30 min before an oral dose of L-CPA (750
      mg/kg) prevented the loss of both granule and Purkinje cells. There was no
      abnormal locomotor activity in the L-CPA rats treated with MK-801 except for the
      first 4 hr following dosing when animals were severely sedated. Animals which
      received L-CPA plus MK-801 were normal 96 hr post dosing showing that MK-801 did
      not delay the onset of L-CPA toxicity. There was no alteration in cerebellar
      water content or sodium concentrations in rats which had been administered MK-801
      with L-CPA. The reductions in cerebellar aspartate and glutamate concentrations
      were totally prevented by administration of MK-801, as was the reduction in L(
      )[3H]glutamate binding to cerebellar NMDA receptors. Administration of MK-801
      alone (5 mg/kg/i.p.) did not alter the water content, sodium concentrations,
      aspartate or glutamate concentrations, or the density of NMDA receptors in the
      cerebellum. In conclusion, we suggest that L-CPA-induced neurotoxicity leading to
      loss in granule cells and an accompanying cerebellar edema can be prevented by MK
      801, suggesting that a subpopulation of NMDA receptors found on cerebellar
      granule cells play a pivotal role in mediating the toxicity of this compound.

PMID- 8560469
TI  - Biotransformation of acrolein in rat: excretion of mercapturic acids after
      inhalation and intraperitoneal injection.
AB  - Biotransformation of acrolein (ACR) was studied in vivo in the rat following
      inhalation and ip administration. The major and minor urinary metabolites were 3
      hydroxypropylmercapturic acid (HPMA) and 2-carboxyethylmercapturic acid (CEMA),
      respectively. Male Wistar rats were exposed to ACR, 23, 42, 77 and 126 mg/m3, for
      1 hr. The sum of mercapturic acids HPMA and CEMA excreted within 24 hr after the
      exposure amounted to 0.87 +/- 0.12, 1.34 +/- 0.5, 2.81 +/- 1.15, and 7.13 +/-
      1.56 mumol/kg, i.e., 10.9 +/- 1.5, 13.3 +/- 5.0, 16.7 +/- 6.9, and 21.5 +/- 4.8%
      of the estimated absorbed dose, respectively. The dose estimate was based on
      reported values of minute respiratory volume and respiratory tract retention and
      was corrected for the ACR-induced changes in minute respiratory volume. In the
      relevant dose range (8.9 to 35.7 mumol/kg) the portion of mercapturic acids
      excreted was nearly constant for ip exposed rats. The sum of HPMA and CEMA
      amounted to 29.1 +/- 6.5% of the dose. These results indicate that the deficiency
      in rat lung metabolism of ACR to acrylic acid previously observed is not
      compensated by the other detoxication pathway in vivo, mercapturic acid
      formation. The health hazard arising from inhalation of ACR is likely to be
      higher than that from other routes of exposure.

PMID- 8560468
TI  - Protective effects of garlic and related organosulfur compounds on acetaminophen
      induced hepatotoxicity in mice.
AB  - In previous studies, we have demonstrated that diallyl sulfide, a flavor
      component of garlic, protects against chemically induced hepatotoxicity. The
      present study examined the activities of fresh garlic homogenates (FGH) and
      related organosulfur compounds in the protection against acetaminophen (APAP)
      induced hepatotoxicity and the possible mechanisms involved in this protection.
      When FGH (5 g/kg) was administered to Swiss-Webster mice 2 hr prior to, or
      immediately after, an APAP treatment (0.2 g/kg), APAP-induced hepatotoxicity was
      essentially prevented as indicated by serum levels of alanine aminotransferase
      and lactate dehydrogenase and by liver histopathology. Partial protection was
      observed with a lower dose of FGH (0.5 g/kg). FGH also prevented APAP-induced
      hepatic glutathione depletion in a dose-dependent manner. FGH significantly
      inhibited the formation of APAP-oxidized metabolites, as indicated by decreased
      plasma levels of oxidized APAP metabolites. The amount of APAP excreted as
      oxidized metabolites in the 24 hr urine samples was also significantly lower in
      the mice pretreated with FGH. FGH supernatant inhibited cytochrome P450-dependent
      APAP oxidation in microsomal incubations. The results suggest that the protection
      against APAP-induced hepatotoxicity by FGH is mainly due to its inhibition of
      P450-mediated APAP bioactivation. Several garlic-derived organosulfur compounds
      and structurally related compounds were examined for their abilities to protect
      against APAP-induced hepatotoxicity. An S-allyl structure appears to be a common
      feature for most sulfides to inhibit P450 2E1-dependent activity and to display
      good protective activities.

PMID- 8560470
TI  - Acetaminophen nephrotoxicity in the CD-1 mouse. II. Protection by probenecid and
      AT-125 without diminution of renal covalent binding.
AB  - Acetaminophen (APAP) administration (600 mg/kg, ip) to 18-hr fasted, 3-month-old
      male CD-1 mice results in necrosis of the convoluted renal proximal tubules with
      a corresponding elevation of plasma urea nitrogen (BUN). Administration of the
      gamma-glutamyl transpeptidase inhibitor, L-(alpha S,5S)-alpha-amino-3-chloro-4,5
      dihydroxy- 5-isoxazoleacetic acid (AT-125) (50 mg/kg, ip), to mice 30 min before
      APAP significantly diminished the APAP-induced histopathologic damage and BUN
      elevation. Administration of the organic-anion transport inhibitor, probenecid
      (150 mg/kg, ip), 30 min before APAP challenge also protected against the APAP
      induced elevation of BUN and detectable histopathologic changes. By contrast,
      pretreatment of mice with the cysteine conjugate beta-lyase inhibitor,
      (aminooxy)acetic acid (100 mg/kg, ip), 1 hr before APAP did not alter
      nephrotoxicity. None of the pretreatments altered the APAP-induced elevation of
      plasma sorbitol dehydrogenase activity, nor were there any detectable changes in
      liver histopathology after APAP challenge. Despite the protective effects of both
      probenecid and AT-125 against nephrotoxicity, they did not affect either the
      level of immunochemically detectable covalent binding to protein or the depletion
      of renal glutathione at 4 hr after APAP. Thus, the protection appears independent
      of effects on renal APAP uptake or activation and indirectly suggests that an
      APAP-glutathione conjugate may contribute to the observed nephrotoxicity.

PMID- 8560472
TI  - Ototoxicity of tobramycin in young adult and old rats.
AB  - To study the possible age-dependent ototoxic effects of tobramycin a subacute
      toxicity study was performed. To young adult (3 months) and old (27-30 months)
      female Wag-Rij rats 0, 10, 40, and 160 mg tobramycin sulfate/kg was administered
      subcutaneously in two doses a day. After 14 days all animals were autopsied. The
      cochlea was fixed by perfusion through the opened oval window and prepared for
      scanning electron microscopy. The rat cochlea consists of two turns. In all
      animals of the young control group the row of inner hair cells (IHC) as well as
      the three rows of outer hair cells (OHC) of the organ of Corti were fully intact.
      IHC as well as OHC are provided with three rows of stereocilia, from inside to
      outside with increasing length. The stereocilia of OHC are arranged in a
      characteristic W-configuration. In the young low dose group effects were focally
      seen in only 1 of 10 rats, consisting of shortened, disoriented or partly
      disappeared stereocilia of IHC and OHC in the basal turn. In the young mid dose
      group 4 of 10 animals had focally shortened, disoriented, and less stereocilia in
      the first row of OHC in the basal turn, and once of IHC and OHC in the apical
      turn. Seven of 8 animals of the young high dose group showed effects consisting
      of focal loss or shortening of stereocilia of IHC and OHC of the apical turn
      (3x), of OHC in the basal turn (3x), and once of stereocilia of IHC only. In the
      old control group the stereocilia of IHC were fully intact. However, many OHC,
      independent of row or turn, had no stereocilia at all. The percentages of OHC
      without stereocilia in the three rows of the apical and basal turns were 44-10-50
      and 40-20-50, respectively. In the old low, mid, and high dose group the
      percentages of OHC without stereocilia were nearly identical to those of the old
      control group. In the old low and high dose group a reduced number of stereocilia
      per IHC occurred in half of the number of animals, while in the mid dose group
      the IHC were fully intact. In young adult animals the number of mildly affected
      cochleae increased as well as the extent of the lesion increased with increasing
      dose of tobramycin. The lesions of IHC and OHC, consisting of a decrease in
      number or shortening of stereocilia, were restricted mainly to (the last part of)
      the basal turn. As old control rats showed already a large number of OHC without
      stereocilia, the possible ototoxic effects of tobramycin were not detected
      against this "background" of stereociliary loss, consistent with aging. The
      damage in old rats was certainly not greater than in young adult rats. In
      conclusion, old rats were not more sensitive to the possible ototoxic effects of
      tobramycin than young adult rats.

PMID- 8560471
TI  - Effects of acute acetaldehyde, chronic ethanol, and pargyline treatment on
      agonist responses of the rat aorta.
AB  - The purpose of this investigation was to determine the mechanism(s) underlying
      the vasorelaxant effects of acute versus chronic acetaldehyde (ACA) exposure, in
      particular, the role of intact endothelium on contractile responses of rat aortic
      ring segments to potassium chloride (KCl) or norepinephrine (NE). The acute
      effects of ACA were assessed in preparations from normal animals maintained on a
      standard rat chow (non-ethanol-ingesting). The monoamine oxidase inhibitor,
      pargyline, elevates plasma ACA levels by decreasing acetaldehyde dehydrogenase
      activity. Accordingly, preparations from pargyline-treated ethanol-ingesting
      animals (PE) were used to assess the effects of chronic (12 weeks) ACA and
      results were compared to those of pargyline-treated non-ethanol-ingesting (P)
      rats fed a standard liquid diet. In normal and P preparations, maximal inotropic
      response to KCl and NE were greater in endothelium-denuded than in endothelium
      intact preparations. However, in aortic rings obtained from PE rats, the maximal
      inotropic response to KCl was depressed only in endothelium-denuded rings and
      that to NE was nearly identical in endothelium-denuded compared to endothelium
      intact preparations. Acute ACA (30 mM) exposure significantly reduced both NE-
      and KCl-induced contractile responses in muscles from all groups. The magnitude
      of the vasorelaxant effect of this [ACA] on NE-induced responses was endothelium
      independent and was similar between groups. However, the vasorelaxant effect of
      ACA (30 mM) on KCl-induced contractile responses was significantly attenuated in
      muscles from PE animals with greater inhibition occurring in endothelium-denuded
      preparations. These results suggest that chronic acetaldehyde exposure leads to
      an impairment in the inotropic response to membrane depolarization in endothelium
      denuded preparations resulting in depressed responsiveness. In addition, the
      acute vasorelaxant effect of ACA on KCl-induced contractures is significantly
      attenuated in preparations chronically exposed to ACA which suggests a possible
      development of tolerance.

PMID- 8560473
TI  - Metabolic deglucuronidation and demethylation of estrogen conjugates as a source
      of parent estrogens and catecholestrogen metabolites in Syrian hamster kidney, a
      target organ of estrogen-induced tumorigenesis.
AB  - Estrogen-induced tumors in kidneys of male Syrian hamsters have been postulated
      to arise from cells which are damaged by free radicals and other reactive species
      generated during metabolic redox cycling of catecholestrogens and which at the
      same time are exposed to excessive growth stimulation mediated by estrogen
      receptors. In this study, we have determined the rates of metabolic deconjugation
      of estrogen glucuronides and of catecholestrogen methyl ethers by cellular
      fractions from male hamster kidney and liver to evaluate the contribution of this
      process to renal pools of parent estrogens and of catecholestrogen metabolites.
      Lysosomes from male hamster kidney catalyzed the deconjugation of estradiol- and
      estrone-3 beta-D-glucuronides at rates of 51.7 and 64.6 pmol/mg protein/min,
      respectively, which were 65 and 34% higher than corresponding deconjugation rates
      by liver lysosomes. Treatment of hamsters with estradiol implants for 9 days
      increased lysosomal glucuronidase activities for these estrogen glucuronides by
      15 to 25% in kidney and doubled the activities in liver, but it did not alter
      their corresponding Km values. Microsomal glucuronidase activities in kidney and
      liver were approximately 10 to 20% of lysosomal activities. Rates of
      demethylation of 2- and 4-methoxyestradiol by kidney microsomes were comparable
      (with Vmax values of 24 and 30 pmol/mg protein/min, respectively), whereas the
      rate of demethylation of 2-methoxyestradiol by liver microsomes was approximately
      fivefold higher than that of 4-methoxyestradiol. The rates of renal demethylation
      of methoxyestrogens were comparable with previously published rates of renal
      aromatic hydroxylation of estradiol, whereas rates of hepatic demethylation were
      about one-fifth of the corresponding hydroxylation rates. It is concluded that
      metabolic deconjugation is an important source of primary estrogens and of
      catecholestrogen metabolites in hamster kidney, a target of estrogen-induced
      tumorigenesis. The increased renal estrogen glucuronidase activity during
      prolonged estradiol treatment may also facilitate the development of estrogen
      induced tumors in this target organ.

PMID- 8560474
TI  - Toxicokinetics of parathion and paraoxon in rainbow trout after intravascular
      administration and water exposure.
AB  - Fish are less sensitive than mammals to organophosphate insecticide toxicity. The
      species differences have been mainly investigated by biochemical studies of AChE
      and organophosphate interaction. To examine whether species differences in the
      toxicokinetics of the organophosphate insecticides were also involved in their
      differential toxicity, rainbow trout were fitted with a dorsal aorta cannula and
      administered parathion and its active metabolite paraoxon intraarterially (ia)
      and via water exposure. Serial blood samples were removed and the plasma
      concentrations of parathion and paraoxon were determined by capillary GC with EC
      detection. Plasma protein binding was determined by equilibrium dialysis and
      ultrafiltration. After ia injection the plasma concentration-time profiles of
      parathion and paraoxon were multiexponential, with a terminal t1/2 of 56.1 and
      0.528 hr. The steady-state volumes of distribution and total body clearances
      (CLb) for parathion and paraoxon were 1370 and 1080 ml kg-1 and 21.4 and 3020 ml
      hr-1 kg-1; the plasma unbound fractions were 1.23 and 52.5%. The large difference
      in CLb between parathion and paraoxon appeared to result primarily from
      differences in plasma protein binding. Parathion had greater persistence in trout
      than rat, suggesting that sensitivity difference were unrelated to toxicokinetic
      differences.

PMID- 8560475
TI  - Modification of acetylcholinesterase during adaptation to chronic, subacute
      paraoxon application in rat.
AB  - These experiments examined the changes in acetylcholinesterase (AChE) during
      tolerance development in rats exposed to paraoxon, an irreversible inhibitor of
      AChE. Rats were injected sc for 20 days with 0.09, 0.12, or 0.19 mg/kg of
      paraoxon. Tolerance to the clinical signs of paraoxon toxicity developed rapidly.
      The hypothesis was tested that changes in the kinetics of reactivity of AChE with
      its substrate acetylcholine (ACh) and the inhibitor paraoxon contribute to the
      observed tolerance. The kinetic constants Vmax and Km were determined by
      Lineweaver-Burk transformations. The affinity (Kd), phosphorylation (kp) and the
      bimolecular rate (ki) constants were established from slopes and standard
      deviations of inhibition curves. Acetylcholinesterase properties of brain and
      diaphragm from controls and paraoxon-tolerant rats were compared. In controls,
      Km, determining the affinity of AChE for ACh, was 0.063 x 10(-3) M and 0.072 x
      10(-3) M for diaphragm and brain, respectively. In paraoxon-tolerant rats, the
      affinity of AChE for ACh increased since the Km for diaphragm was reduced to
      0.047 x 10(-3) M and the Km for brain to 0.057 x 10(-3) M. This decrease was seen
      with all paraoxon concentrations and was significantly different from controls
      after the fifth day of treatment. Small, significant increases of IC50 values for
      paraoxon were observed in diaphragm (from 27.30 to 45.14 nM) and in brain (from
      13.67 to 15.38 nM). In brain, a 20-day treatment with paraoxon caused a fivefold
      decrease in the dissociation constant (Kd) from 1.56 to 0.268 microM and a
      threefold decrease in the phosphorylation constant (kp) from 4.72 to 1.52 min-1.
      The observed changes in diaphragm were smaller and not significant. The increase
      in affinity to ACh gives an advantage to tolerant rats, because the remaining
      reduced amount of AChE can hydrolyze ACh more efficiently, regardless of the
      change in sensitivity to the inhibitor. The observed changes may be the result of
      structural changes of AChE or the result of altered levels of preexisting
      isozymes of AChE.

PMID- 8560476
TI  - Rat hepatocytes with elevated metallothionein expression are resistant to N
      methyl-N'-nitro-N-nitrosoguanidine cytotoxicity.
AB  - Metallothionein (MT) is a small cysteine-rich metal-binding protein involved in
      Zn and Cu homeostasis as well as in heavy metal detoxication. It is also believed
      that when MT is overexpressed, it can confer resistance against alkylating
      agents. However, the mechanisms involved are still poorly understood. The purpose
      of the present work was to investigate whether metal treatment, which induces MT
      synthesis, could protect isolated rat hepatocytes against the cytotoxic effects
      of the alkylating agents methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG). Exposure to 12.5 microM ZnSO4 for 18 hr raised MT levels
      approximately 15-fold (as measured by the 109Cd-heme assay). When these cells
      were exposed to increasing concentrations of MNNG, a significant reduction in
      cell death (as measured by lactate dehydrogenase leakage into extracellular
      medium) was observed (LC50 = 468 +/- 20 microM vs 362 +/- 13 microM for control
      cells). On the other hand, Zn pretreatment was not accompanied by resistance
      against MMS toxicity. In addition, the synthesis of graded amounts of MT,
      achieved by incubation with various concentrations of Zn or Cu, led to a high
      correlation between MT levels and the extent of hepatocyte survival. Cd (another
      MT inducer) failed to protect hepatocytes from MNNG cytotoxicity. Time-course
      studies also revealed a good correlation between the onset of MT induction by Zn
      (> 3 hr) and that of protection against MNNG (> 3 hr). The stability of MT in the
      presence of MNNG was studied by incubating 109Cd-labeled MT with MNNG and by
      analyzing the mixture using Sephadex G-75 Chromatography. Direct interaction of
      MNNG with rabbit liver (Cd,Zn)-MT was demonstrated by the release of 109Cd bound
      to MT. Similar results were obtained with 109Cd-exposed hepatocytes, 109Cd being
      redistributed from MT to high-molecular-weight proteins after incubation with
      MNNG. None of the metals used to induce MT modulated glutathione (GSH) because it
      remained at control levels after 18 hr. However, within 15 min of incubation,
      MNNG had completely depleted GSH in both control and Zn-pretreated hepatocytes
      equally. This was followed by a marked decline in MT levels. Taken together,
      these results suggest that Zn- and Cu-induced tolerance against killing by MNNG
      appears to be related to the accumulation of MT. The mechanism of protection
      might reside in the antioxidant properties of MT and on its ability to scavenge
      electrophilic species.

PMID- 8560477
TI  - Effect of agents which modify reticuloendothelial system function on acute
      phalloidin-induced lethality and hepatotoxicity in mice.

PMID- 8560478
TI  - A mechanistic model of effects of dioxin on thyroid hormones in the rat.
AB  - A physiological dosimetric model of the disposition of TCDD in the rat (Kohn et
      al., Toxicol. Appl. Pharmacol. 120, 138-154, 1993) was extended to include
      effects of dioxin on serum concentrations of thyroid hormones in the rat. The
      extended model included distribution of blood among major vessels and tissue
      capillary beds and resorption of TCDD released into the gut lumen from the liver
      by cell lysis consequent to cytotoxicity. TCDD metabolism was represented by Hill
      kinetics. Parameter values were estimated by fitting time-course data for a
      single oral subcutaneous injection of TCDD and dose-response data for biweekly
      oral dosing. The extended model included new compartments for the thyroid and
      thyroxine-sensitive tissues (e.g., pituitary, kidney, and brown fat), secretion
      and tissue uptake of thyroid hormones, binding of 3,5,3'-triiodothyronine (T3)
      and 3,5,3',5'-tetraiodothyronine (thyroxine, T4) to proteins in blood and
      tissues, deiodination of iodothyronines, and glucuronidation of T4 by the hepatic
      UDP-glucuronosyltransferase (UGT) activity induced by TCDD. Secretion of thyroid
      hormones was modeled as regulated by thyrotropin (TSH), whose secretion was
      modeled as regulated by the hypothalamic factors thyrotropin releasing hormone
      and somatostatin. Release of the hypothalamic factors was modeled as under
      feedback control by the blood T4 level. Induction of UGT was modeled as
      stimulated by the Ah receptor-TCDD complex. The extended model fit the observed
      dose-response of P450 isozymes and Ah and estrogen receptors following repeated
      oral doses with comparable accuracy as the earlier model. The fit to liver and
      fat TCDD levels following single and repeated oral and subcutaneous doses was
      improved over the earlier model. The revised model's predicted liver TCDD
      concentrations at very low doses were verified experimentally. The model
      reproduced the responses observed for blood T3, T4, and TSH after 31 weeks of
      biweekly oral dosing of rats with TCDD. The model also predicted responses of UGT
      mRNA and UGT enzymatic activity comparable to those observed in TCDD-treated rats
      in experiments whose data were not used in constructing the model. Calculated
      increases in blood TSH levels are consistent with prolonged stimulation of the
      thyroid and may represent an early stage in the induction of thyroid tumors
      identified in previous two-year bioassays. Thus, increases in UGT activity may be
      useful as a biomarker for tumorigenic changes in hormone levels subsequent to
      TCDD exposure.

PMID- 8560479
TI  - Differences in rates of benzene metabolism correlate with observed genotoxicity.
AB  - Benzene (BZ) requires oxidative metabolism via cytochrome P450 2E1 (CYP 2E1) to
      exert its hematotoxic and genotoxic effects. Male mice are two- to threefold more
      sensitive to the genotoxic effects of BZ as measured by micronuclei induction and
      sister chromatid exchanges. The purpose of our study was to investigate sex
      related differences in the metabolism of BZ, phenol (PHE) and hydroquinone (HQ)
      in order to understand the metabolic basis for sex-dependent differences in BZ
      genotoxic susceptibility in mice. Rates of BZ oxidation were quantitated using
      closed chamber gas uptake studies with male and female B6C3F1 mice exposed to
      initial low (400-500 ppm), intermediate (1200-1300 ppm), and high (2600-2800 ppm)
      BZ concentrations. Acetone-pretreated and diethyldithiocarbamate-pretreated male
      mice were also studied to determine the extent to which induction and inhibition
      of CYP 2E1, respectively, would alter in vivo BZ oxidation rates. Elimination of
      PHE and HQ from blood was also compared in male and female mice to complement
      previously reported data on sex-related differences in urinary excretion of
      conjugated metabolites following iv administration of PHE. Based on PBPK model
      analysis, the optimized rate of metabolism (Vmax) of BZ was almost twofold higher
      in male mice (14.0 mumol/hr-kg) than in female mice (7.9 mumol/hr-kg); both male
      and female mice gas-uptake data were well fit with a KM of 3.0 microM.
      Pretreatment of male mice with 1% acetone in drinking water for 8 days to
      specifically induce CYP 2E1 enhanced the rate of BZ oxidation by approximately
      fivefold (Vmax = 75 mumol/hr-kg), while diethyldithiocarbamate pretreatment (320
      mg/kg ip 30 min prior to uptake study) completely inhibited BZ oxidation (Vmax =
      0 mumol/hr-kg). Thus, both pretreatment regimens are potentially useful
      investigative tools to study the metabolic basis for benzene toxicity.
      Elimination of PHE from blood was significantly faster in male mice, while
      elimination of HQ did not differ between male and female mice. Previous data
      indicated male mice produce more of the oxidized and conjugated metabolite, HQ
      glucuronide, after PHE administration, suggesting that HQ production from PHE is
      greater in male mice. Taken together, these data support the hypothesis that the
      greater sensitivity of male mice to the genotoxic effects of BZ compared to
      females is a function of greater oxidative metabolism toward both BZ and PHE in
      male mice. These data also suggest that differences in hepatic human CYP 2E1
      activity may be an important factor to consider when evaluating human risk for
      benzene-induced hematotoxic and genotoxic effects.

PMID- 8560480
TI  - Changes in cerebellar amino acid neurotransmitter concentrations and receptors
      following administration of the neurotoxin L-2-chloropropionic acid.
AB  - 1p4studied the effect of L-2-chloropropionic acid (L-CPA)-induced (250
      mg/kg/po/day for 3 days) neurotoxicity, which results in an almost total
      destruction of cerebellar granule cells over 5 days, on forebrain and cerebellar
      neurochemistry. There was a reduction in cerebellar aspartate and glutamate
      concentrations of L-CPA-treated rats and a reduction in N-methyl-D-aspartate
      (NMDA) and kainate receptor densities in the cerebellar cortex following loss of
      the granule cells. Concentrations of glutamine and GABA were increased
      transiently during the development of the granule cell lesion but fell back to
      control levels by Day 5 of the study. Glycine concentrations began to rise as the
      granule cells began to disappear and concentrations remained elevated until the
      end of the study. In contrast, concentrations of taurine began to fall around the
      same time point as the granule cells were gradually depleted. We did not observe
      any consistent changes in forebrain amino acid concentrations following the L-CPA
      administration or any changes in NMDA, kainate, GABAA, or A1-adenosine receptor
      densities. We therefore conclude that the L-CPA-induced loss in cerebellar
      granule cells is accompanied by a reduction in cerebellar aspartate and glutamate
      concentrations and in the density of NMDA and kainate receptors in the cerebellar
      cortex. Changes in cerebellar GABA, glutamine, glycine, and taurine
      concentrations probably reflect secondary compensatory changes in cerebellar
      activity resulting from a widespread loss of cerebellar granule cells and loss of
      excitatory inputs. We suggest that L-CPA-induced neurotoxicity may be valuable
      tool to study cerebellar neurochemistry and physiology.

PMID- 8560481
TI  - Epidermal cytokinetics, DNA adducts, and dermal inflammation in the mouse skin in
      response to repeated benzo[a]pyrene exposures.
AB  - Few studies have investigated the chronic cytokinetic effects of carcinogen
      exposure in the mouse skin. We report two experiments involving the repeated
      application of benzo[a]pyrene (BaP) to the dorsal skin of female Ha/ICR mice. In
      the first experiment, the cytokinetic, inflammatory, and DNA adduct responses
      were studied daily over a 9-day period encompassing the fourth and fifth weekly
      applications of BaP at doses of 16, 32, and 64 micrograms. The second experiment
      involved the same cytokinetic measurements at 1, 3, 5, and 8 months, and the
      weekly BaP doses were 4, 8, and 16 micrograms. The first study showed that after
      each application of 32 or 64 micrograms BaP, there was a wave of slow DNA
      synthesis in the epidermis which peaked at 24 hr, in coincidence with a wave of
      BaP-DNA adducts, followed by the appearance of dead and damaged keratinocytes.
      For the first few days after BaP application there was a depression in the
      mitotic rate which recovered several days before the next BaP application. There
      was a predominantly monocytic dermal inflammation throughout the observation
      period. In the second experiment, at the lower BaP doses, there was proliferative
      depression at 1 month, without dermal inflammation. With continued exposure, the
      proliferative depression changed to a dose-dependent increase in the rate of
      proliferation and dermal inflammation. The level of BaP-DNA adducts was followed
      in the 4 micrograms/week dose group, which showed a threefold increase after 4
      months with the appearance of inflammation and heightened cell proliferation.
      These results suggest that the delayed inflammatory reaction, possibly based on a
      cell-mediated immune reaction to BaP, might have been responsible for the late
      cytokinetic responses and the associated increase in the level of BaP-DNA
      adducts.

PMID- 8560482
TI  - Pharmacokinetics and interspecies scaling of recombinant human factor VIII.
AB  - Recombinant human (rh) factor VIII is a glycoprotein consisting of multiple
      polypeptides with relative mobilities (M(r)) ranging from 80,000 to 210,000. It
      is produced in mammalian cells. Single-dose intravenous pharmacokinetic studies
      were conducted with rh factor VIII (Kogenate rh Antihemophilic Factor, Miles,
      Inc.) in male mice (21.0-25.8 g) and rats (252.0-254.2 g). Each species received
      400 IU/kg, and blood was collected up to 12 hr (mice) or 32.5 hr (rats) post
      dose. Immunoreactive factor VIII concentrations in plasma were quantified by a
      sensitive and specific ELISA. In both species, the disposition profiles were
      described by the sum of two exponentials. The pharmacokinetics of rh factor VIII
      in mouse were as follows: clearance, 27.7 ml/hr/kg; initial volume of
      distribution, 72 ml/kg; steady-state volume of distribution, 148 ml/kg; and
      terminal half-life, 4.1 hr. In rat, the mean estimates were as follows:
      clearance, 16.0 ml/hr/kg; initial volume of distribution, 41 ml/kg; steady-state
      volume of distribution, 125 ml/kg; and terminal half-life, 5.5 hr. These
      pharmacokinetic parameters for rh factor VIII in animals and human rh factor VIII
      pharmacokinetic parameters from the literature were evaluated to determine if the
      parameters can be represented by the allometric relationship, Y = aWb, where Y is
      the pharmacokinetic parameter, and W is body weight. The following allometric
      relations were obtained for rh factor VIII: clearance (ml/hr) = 10.4W0.69, half
      life (hr) = 7.5 W0.18, initial volume of distribution (ml) = 43.6 W1.04, and
      steady-state volume of distribution (ml) = 99.1 W0.84. The allometric exponents
      for each parameter conformed to theory and were within the range of values
      commonly observed for xenobiotics and therapeutic proteins. These studies suggest
      that the pharmacokinetics of rh factor VIII in laboratory animals are predictive
      of the disposition in humans despite the complex nature of its biological
      interactions and the chemical diversity of the purified material.

PMID- 8560483
TI  - Modulation by iron of hepatic microsomal and nuclear cytochrome P450, and
      cytosolic glutathione S-transferase and peroxidase in C57BL/10ScSn mice induced
      with polychlorinated biphenyls (Aroclor 1254).
AB  - Exposure of iron-loaded C57BL/10ScSn mice to the polychlorinated biphenyls (PCBs)
      mixture Aroclor 1254 in the diet (0.01%) for 5 weeks caused massive hepatic
      porphyria far greater than occurred with PCBs alone. This regime eventually
      causes hepatocellular carcinoma. Hepatic microsomal ethoxy-, pentoxy-, and
      benzyloxyresorufin dealkylase activities (respectively EROD, PROD, and BROD)
      catalyzed primarily by cytochrome P4501A1 and 2B isoenzymes were markedly induced
      after 2 weeks of diet (when no porphyria had developed) but showed little effect
      of iron. EROD activity in the nuclear membrane was also induced by the PCBs as
      was CYP1A1 protein when shown by immunoblotting. Nuclear dealkylase activities of
      PCBs-treated mice were considerably less than microsomal activities but were
      stimulated by iron pretreatment. The mechanism of the iron-enhanced toxicity may
      be due to oxidative damage associated with chronic induction of CYP1A1 isoforms.
      Lucigenin-enhanced chemiluminescence (CL) by microsomes and nuclear membranes was
      used as a method to estimate their potential to form reactive oxygen species.
      Despite CL being induced by PCBs it was less with microsomes from iron-treated
      mice. In a comparison of a variety of inducers of microsomal cytochrome P450
      there was no correlation between inducer, uroporphyrogenic agent, and intensity
      of CL. On the other hand, cytosolic glutathione S-transferase (GST) activities
      with 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene (DCNB) as
      substrates, were also induced by the PCBs mixture, the induction with DCNB being
      synergistically potentiated by iron pretreatment. Complementary results were
      observed by immunocytochemistry using anti alpha-GST antibody. In contrast, total
      glutathione peroxidase activity and selenium-dependent glutathione peroxidase
      activity were depressed by PCBs but particularly in mice also administered iron.
      The results illustrate that PCBs not only induce CYP1A1 in microsomes but also in
      the nuclear membrane, which may be of significance in the mechanism of the iron
      enhanced carcinogenicity of these chemicals. The iron-enhanced induction of GST
      with accompanying depletion of glutathione peroxidase provides evidence for
      oxidative processes induced in vivo by the PCBs.

PMID- 8560484
TI  - In vivo and in vitro kinetics of ethylene oxide metabolism in rats and mice.
AB  - Ethylene oxide (EO) is a direct-acting mutagen and animal carcinogen used as an
      industrial intermediate and sterilant with a high potential for human exposure.
      Kinetics of EO metabolism in rodents can be used to develop human EO dosimetry
      models. This study examined the kinetics of EO metabolism in vivo and in vitro in
      male and female F-344 rats and B6C3F1 mice. In vivo studies measured blood and
      tissue EO levels during and 2-20 min following whole-body inhalation exposure (4
      hr, 100 or 330 ppm EO). At 100 ppm EO, the half-life of elimination (t1/2) in
      rats was 13.8 +/- 0.3 (mean +/- SD) and 10.8 +/- 2.4 min for males and females,
      respectively, compared to a t1/2 in mice of 3.12 +/- 0.2 and 2.4 +/- 0.2 min in
      males and females, respectively. On exposure to 330 ppm EO, the t1/2 in mice
      increased approx twofold, while no change in t1/2 was observed in rats. In vitro
      kinetic parameters (Vmax and KM) of EO metabolism were determined using tissue
      cytosol and microsomes. EO metabolism in vitro occurred primarily via cytosolic
      glutathione S-transferase-mediated EO-GSH conjugation (cGST-EO), with highest
      activity in the liver. Liver cGST-EO activity (Vmax) was 258 +/- 86.9 and 287 +/-
      49.0 nmol/mg protein/min (mean +/- SD) in male and female mice, respectively,
      compared to 52.7 +/- 10.8 and 29.3 +/- 4.9 in male and female rats, respectively.
      In rats, but not mice, there was a statistically significant (p < 0.05) gender
      difference in the Vmax for liver cGST. The KM for liver cGST-EO was approximately
      10 mM in both species. The higher Vmax values observed in mice are consistent
      with the more rapid elimination of EO observed for this species in vivo compared
      to rats.

PMID- 8560485
TI  - Alterations in nuclear ploidy and cell phase distribution of rat liver cells in
      experimental alcoholic liver disease: relationship to antioxidant enzyme gene
      expression.
AB  - The ability of a cell to withstand oxidative stress has been hypothesized to be
      related to its ploidy status. We used the intragastric feeding rat model for
      alcoholic liver disease to evaluate the relationship between severity of liver
      injury, antioxidant mRNA levels, and DNA ploidy of liver cells. Rats were fed
      ethanol with different dietary fats (saturated fat, corn oil, and fish oil); pair
      fed control animals received isocaloric amounts of dextrose. All animals were
      euthanized at 1 month and had evaluation of pathologic changes in the liver, DNA
      content by flow cytometry, and mRNA levels for catalase and glutathione
      peroxidase. The fish oil-ethanol group exhibited the most severe pathology, the
      corn oil-ethanol group had intermediate pathologic changes, and no pathologic
      changes were seen in the saturated fat-ethanol and dextrose-fed controls. Flow
      cytometric analysis of propidium iodide-stained nuclei revealed that saturated
      fat-dextrose and corn oil-dextrose groups had about 65% of cells with (diploid)
      G1 DNA content and about 30% of cells with tetraploid (4C) nuclei. The fish oil
      dextrose had a significantly higher (p < 0.001) number of 4C cells (67.4 +/-
      2.1%) compared to the other two dextrose-fed groups. In the animals showing
      pathologic liver injury, there was a higher percentage of cells with
      hypertetraploid nuclei. The highest percentage of these hypertetraploid cells was
      seen in the fish oil-ethanol group. Catalase and glutathione peroxidase mRNA
      levels correlated significantly with polyploidy. A significant correlation was
      seen between the number of cells in the greater than G2 + M phase and glutathione
      peroxidase mRNA levels (r = 0.91, p < 0.01) and catalase mRNA. The different
      slopes of correlation analysis between catalase mRNA and dietary fats show that
      the degree of saturation of fatty acids may influence catalase mRNA expression in
      cells with different ploidy states. We propose that polyploidization of liver
      cell nuclei may serve as a defense mechanism against ethanol-induced
      hepatotoxicity. This defense mechanism may also, in part, account for the
      antiregenerative effect of ethanol on hepatocytes.

PMID- 8560486
TI  - Induction of metallothionein mRNA and protein in murine astrocyte cultures.
AB  - Astrocytes are known to express metallothionein (MT) and were studied in culture
      to determine whether MT could be directly induced and which isoforms are induced.
      Primary astrocyte cultures were established from neonatal CF-1 mice. Both
      concentration-response and time-course analyses for MT induction at the protein
      level were determined. At the mRNA level, induction of MT-I, -II, and -III was
      examined 6 hr following the addition of the inducing agents. Dexamethasone (Dex),
      cadmium (Cd), mercury (Hg), or zinc (Zn) increased (three- to fourfold) MT
      protein in the astrocytes, whereas methyl mercury, lead, and interleukin-1 and -6
      were ineffective. Cadmium was the most potent inducer, but was not more effective
      than Hg or Zn in inducing MT protein. All effective inducers increased MT protein
      by 24 hr. After 48 hr, Hg caused cell death, but all other effective inducers
      increased the MT protein examined over the 5 days. Cadmium induction of MT
      protein reached a peak at 96 hr, whereas the other effective inducers stimulated
      maximal MT protein at 24-48 hr. The effects of Dex, Cd, and Zn, on MT-I, -II, and
      -III mRNAs were also examined. Cadmium, Zn, and Dex stimulated increases in both
      MT-I and MT-II mRNA, with Dex producing the greatest effect (2.0- and 3.5-fold
      for MT-I and -II mRNA, respectively). Metallothionein-III mRNA was relatively
      unresponsive to induction. Therefore, Cd, Zn, and Dex induced MT-I and -II mRNA
      but not MT-III mRNA in astrocytes. These results demonstrate that MT-I and -II
      are directly induced in mouse astrocyte primary cultures.

PMID- 8560487
TI  - Substrates of human hepatic cytochrome P450 3A4.
AB  - Cytochrome P450 isozyme 3A4 (CYP3A4) is a major isozyme in the human liver and is
      known to metabolize a larger variety of xenobiotics and endogenous biochemicals.
      The identities of CYP3A4 substrates are summarized here. A total of 32 chemicals
      belonging to different structural classes have been evaluated and found to be
      substrates for CYP3A4. The metabolic pathways for these substrates include N
      oxidation, C-oxidation, N-dealkylation, O-dealkylation, nitro-reduction,
      dehydration, and C-hydroxylation. While the major experimental system used to
      elucidate the role of CYP3A4 in the metabolic transformation of these substrates
      is the human liver microsome system, cultured human hepatocytes and
      yeast/cultured cells genetically engineered to express CYP3A4 are also employed
      by the different investigators. The common approaches to identify the role of
      CYP3A4 are also summarized, which include correlation of metabolic activity of
      the substrates studied with those for known CYP3A4-catalyzed substrates,
      correlation of activity with CYP3A4 content, inhibition of activity with CYP3A4
      specific antibodies, inhibition of activity with known CYP3A4 substrates and
      inhibitors, induction of activity with CYP3A4 inducers and demonstration of
      activity with purified CYP3A4 enzyme.

PMID- 8560488
TI  - Antagonism of cyanide toxicity by isosorbide dinitrate: possible role of nitric
      oxide.
AB  - In a search for improved cyanide antidotes, the efficacy of isosorbide dinitrate
      (ISDN), was compared with that of the known cyanide antidote, NaNO2. ISDN was as
      effective as an optimal dose of NaNO2 in protecting mice against cyanide
      lethality. To study the mechanism involved, the extent of formation of the
      cyanide scavenger, methemoglobin, in the action of ISDN was determined. ISDN (300
      mg/kg, p.o.) increased methemoglobin from 5 to 10% of total hemoglobin, while, in
      contrast, NaNO2 (100 mg/kg, i.p.) increased methemoglobin levels to 50% of total
      hemoglobin. Lowering the dose of NaNO2 to 30 mg/kg reduced methemoglobin levels
      to approximately 10% of total hemoglobin and in turn nearly abolished its
      antidotal effect. Decreasing methemoglobin to less than control levels using
      methylene blue failed to abolish cyanide antagonism by ISDN. Thus, methemoglobin
      formation by ISDN does not account for its antidotal action. Further studies
      comparing the respiratory depressant effects of cyanide in the presence of ISDN
      or NaNO2 also indicated that these two antidotes have different mechanisms of
      action. Efforts to produce tolerance to the antidotal effect of ISDN against
      cyanide toxicity were unsuccessful. It is suggested that the well-known ability
      of ISDN to generate nitric oxide may account for the noted cyanide antagonism.

PMID- 8560489
TI  - Interactions of cis-fatty acids and their anilides with formyl-methionyl-leucyl
      phenylalanine, phorbol myristate acetate and dioctanoyl-s,n-glycerol in human
      leukocytes.
AB  - Aniline-denaturated rape-seed food oils that contained anilides of linoleic and
      oleic acids caused a poisoning epidemic, known as Toxic Oil Syndrome, in Spain in
      1981. Toxic Oil Syndrome affected mainly the lungs and the immune system of
      exposed individuals. Linoleic and oleic acids, and linoleic and oleic anilides
      increased the production of reactive oxygen metabolites in human
      polymorphonuclear leukocytes. Both cis-fatty acids inhibited a chemotactic
      peptide-, fMLP-induced production of reactive oxygen metabolites without
      affecting fMLP-induced elevation of intracellular calcium levels. Linoleic acid
      anilide slightly amplified fMLP-induced respiratory burst, whereas oleic acid
      anilide was without an effect. However, both fatty acid anilides decreased fMLP
      induced elevation of levels of free intracellular calcium. Moreover, both cis
      fatty acids and their anilides inhibited phorbol myristate acetate (PMA)- and
      dioctanoyl-s,n-glycerol (DiC8)-induced production of reactive oxygen metabolites.
      Thus, both cis-fatty acids and their anilides inhibited agonist-stimulated
      production of reactive oxygen metabolites; this is most likely due to
      interactions with cell signalling events. These results suggest that both
      linoleic and oleic acids and their anilides may inhibit immunological responses
      of leukocytes.

PMID- 8560490
TI  - Isoflurane acts as an inhibitor of oxidative dehalogenation while acting as an
      accelerator of reductive dehalogenation of halothane in guinea pig liver
      microsomes.
AB  - The effects of isoflurane, 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether, on
      the oxidative metabolism of halothane to produce trifluoroacetic acid (TFA) and
      on the reductive metabolism of halothane to produce chlorodifluoroethylene (CDE)
      and chlorotrifluoroethane (CTE) in liver microsomes of guinea pig were examined.
      Isoflurane enhanced the production of CDE and CTE and inhibited the production of
      TFA. Isoflurane enhanced cytochrome P450 reduction and formation of an
      intermediate complex with cytochrome P450 without enhancement of NADPH-cytochrome
      P450 reductase (EC 1.6.2.4) activity. We conclude that isoflurane interacts with
      cytochrome P450 to prevent the formation of the halothane-cytochrome P450
      complex, causing inhibition of the oxidative dehalogenation. This interaction of
      isoflurane enhances the reduction of cytochrome P450 and the formation of a
      reductive intermediate-cytochrome P450 complex under anaerobic conditions causing
      reductive dehalogenation of halothane.

PMID- 8560491
TI  - In vitro and in vivo generation of reactive oxygen species, DNA damage and
      lactate dehydrogenase leakage by selected pesticides.
AB  - Reactive oxygen species may be involved in the toxicity of various pesticides and
      we have, therefore, examined the in vivo effects of structurally dissimilar
      polyhalogenated cyclic hydrocarbons (PCH), such as endrin and chlordane,
      chlorinated acetamide herbicides (CAH), such as alachlor, and organophosphate
      pesticides (OPS), such as chlorpyrifos and fenthion, on the production of hepatic
      and brain lipid peroxidation and DNA-single strand breaks (SSB), two indices of
      oxidative stress and oxidative tissue damage. The selected pesticides were
      administered p.o. to female Sprague-Dawley rats in two 0.25 LD50 doses at 0 h and
      21 h and killed at 24 h. In a parallel set of experiments, we have determined the
      in vitro effects of these pesticides on the DNA-SSB and enhanced lactate
      dehydrogenase leakage (LDH) from neuroactive PC-12 cells in culture. In vitro
      production of reactive oxygen species by these pesticides was also assessed by
      determining the enhanced chemiluminescence responses of hepatic and brain
      homogenates. Following treatment of rats with endrin, chlordane, alachlor,
      chlorpyrifos and fenthion, increases of 2.8-, 3.0-, 4.2-, 4.3- and 4.8-fold were
      observed in hepatic lipid peroxidation, respectively, while at these same doses,
      increases in lipid peroxidation of 2.4-, 2.1-, 3.6-, 4.6- and 5.3-fold,
      respectively, were observed in brain homogenates. Increases of 4.4-, 3.9-, 1.6-,
      3.0- and 3.5-fold were observed in hepatic DNA-SSB following treatment of the
      rats with endrin, chlordane, alachlor, chlorpyrifos and fenthion, respectively,
      while at these same doses, increases of 1.9-, 1.7-, 2.2-, 1.4-, 1.4-fold,
      respectively, were observed in brain nuclear DNA-SSB. Following in vitro
      incubation of hepatic and brain tissues with 1 nmol/ml of each of the five
      pesticides, maximum increases in chemiluminescence occurred within 4-7 min of
      incubation and persisted for over 10 min. Increases of 3.0-, 2.7-, 3.6-, 4.9- and
      4.4-fold were observed in chemiluminescence following in vitro incubation of the
      liver homogenates with endrin, chlordane, alachlor, chlorpyrifos and fenthion,
      respectively, while increases of 1.7-, 1.8-, 2.0-, 3.4- and 3.7-fold,
      respectively, were observed in the brain homogenates. Increases of 2.2-, 2.3-,
      2.9-, 2.9- and 3.4-fold were observed in the chemiluminescence responses in the
      liver homogenates of the animals treated with endrin, chlordane, alachlor,
      chlorpyrifos and fenthion, respectively, while increases of 1.8-, 2.0-, 3.2-, 2.9
      and 2.4-fold, respectively, were observed in the brain homogenates. Cultured
      neuroactive PC-12 cells were incubated with the pesticides and the release of the
      enzyme lactate dehydrogenase (LDH) into the media as an indicator of cellular
      damage and cytotoxicity was examined. Maximal release of LDH from cultured PC-12
      cells was observed at 100 nM concentrations of the pesticides. Increases of 2.3-,
      2.5-, 2.8-, 3.1 and 3.4-fold were observed in LDH leakage following incubation of
      the PC-12 cells with endrin, chlordane, alachlor, chlorpyrifos and fenthion,
      respectively. Following incubation of the cultured PC-12 cells with 100 nM
      concentrations of these same pesticides, increases in DNA-SSB of 2.5-, 2.2-, 2.1
      , 2.4- and 2.5-fold, respectively, were observed. The results clearly demonstrate
      that these different classes of pesticides induce production of reactive oxygen
      species and oxidative tissue damage which may contribute to the toxic
      manifestations of these xenobiotics. Reactive oxygen species may serve as common
      mediators of programmed cell death (apoptosis) in response to many toxicants and
      pathological conditions.

PMID- 8560492
TI  - Heme oxygenase induction by cadmium chloride: evidence for oxidative stress
      involvement.
AB  - Cadmium chloride (CdCl2), a well-known inducer of heme oxygenase, produced a
      strong increase in 'in vivo' rat liver chemiluminescence (QLV) 3 h after
      administration. Heme oxygenase activity increased 5 h after treatment, reaching a
      maximum value around 12-15 h after CdCl2 administration. Such induction was
      preceded by a decrease in the intrahepatic GSH pool and an increase in hydrogen
      peroxide steady-state concentration, both effects taking place several hours
      before induction of heme oxygenase. The activity of antioxidant enzymes,
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)
      was found to be significantly decreased 5 h after CdCl2 injection. Administration
      of bilirubin, the end product of heme catabolism in mammals, and alpha
      tocopherol, a widely employed antioxidant, prevented heme oxygenase induction as
      well as the decrease in hepatic GSH and the increase in chemiluminescence when
      administered 2 h before CdCl2 treatment. These results obtained with CdCl2
      treatment support our recent reports correlating heme oxygenase induction with
      oxidative stress.

PMID- 8560493
TI  - Experiences with an advanced screening procedure for the identification of
      chemicals with an immunotoxic potential in routine toxicology.
AB  - The development or selection of suitable tests for immunotoxicological screening
      and thus for incorporation into guidelines presents some problems. Most of the
      tests which have been proposed for immunotoxicological investigations and most
      knowledge and experience in immunology are based on mouse models. The standard
      species in the early phase of toxicological testing, however, is the rat. Any
      discussion about basic tests is hampered by a paucity of data from routine
      toxicological and/or epidemiological studies. Here we present data obtained from
      an advanced screening battery on the basis of OECD guideline 407. Thirteen
      pesticides of early development stage had been included in this screening. Two
      out of these 13 compounds turned out to be cytotoxic and were picked up by the
      immunological parameters as being 'primary immunotoxic', i.e., immunological
      changes not induced by overtly toxic doses ('indirect or secondary immunotoxic').
      The advantages and disadvantages of each additional test is discussed as well as
      the comparison of the results obtained on the basic and the extended guideline
      test battery. In summary, the tests described here show that a little extra
      effort at the screening stage can save animals, time and costs for additional
      testing.

PMID- 8560494
TI  - Direct exposure to nitrogen dioxide fails to induce the expression of some
      inflammatory cytokines in an IC-21 murine macrophage cell model.
AB  - Biologically-active molecules secreted from alveolar macrophages, such as
      cytokines, have been proposed to be involved in the induction of pulmonary
      toxicity and inflammation in response to the inhalation of oxidant gas pollutants
      such as NO2 and O3. Despite this, mechanistic studies are hampered by the
      difficulty in obtaining control macrophages from human subjects, and the
      intrinsic variability of such primary cells. It is, thus, of importance to
      develop alternative models for such studies. Here, we have characterised
      expression kinetics of the mRNAs for tumour necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1 beta), macrophage inflammatory protein-1 alpha (MIP-1
      alpha) and macrophage inflammatory protein-1 beta (MIP-1 beta) in confluent
      cultures of the murine IC-21 macrophage line in response to LPS. The secretion of
      TNF-alpha protein into the medium, assayed by L-929 cell bioassay, closely
      followed the expression of its mRNA in response to the LPS stimulus. In contrast
      to LPS, the exposure of IC-21 cells to either air or various concentrations of
      NO2 in air between 2 and 20 ppm, in an inverted plate exposure model, failed to
      induce the expression of any of the cytokine mRNAs probed. We conclude that the
      IC-21 cell line may represent a suitable model for studying the role of
      stimulated cytokine gene expression in inflammation and that the early events in
      the pulmonary inflammatory response to the inhalation of NO2 do not involve
      stimulated release of TNF-alpha, IL-1 beta or MIP-1 alpha/MIP-1 beta from
      macrophages.

PMID- 8560495
TI  - Effects of a single dose of the cytochrome P450 inducer, beta-naphthoflavone, on
      hepatic and renal covalent DNA modifications (I-compounds).
AB  - I-compounds are age-dependent covalent DNA modifications, which occur in rodent
      tissues without known carcinogen exposure. A number of studies from our
      laboratory indicate that I-compounds may serve as biomarkers of carcinogenesis.
      Recently, we demonstrated significant lowering of liver I-compound levels in rats
      that were exposed to different cytochrome P450 inducers. In order to gain further
      mechanistic insights into the possible relationship between P450 induction and I
      compound reduction, female Sprague-Dawley rats were administered a single dose of
      the CYP1A1 inducer, beta-naphthoflavone (BNF) (80 mg/kg), in corn oil (CO) (2
      ml/kg) or CO only (2 ml/kg) as vehicle control. Liver and kidney microsomal P450
      contents and P450-related enzyme activities and DNA I-compounds were determined
      at 4, 24, and 48 h after treatment. Liver and kidney I-compounds were analyzed by
      nuclease P1-enhanced 32P-postlabeling. DNA synthesis was determined by measuring
      [3H]methylthymidine incorporation. Liver and kidney microsomal P450 contents were
      elevated by BNF at 24 and 48 h. Ethoxyresorufin-O-deethylase (EROD) and
      methoxyresorufin-O-demethylase (MROD) were significantly elevated at all time
      points, with the former displaying a much higher extent of induction. BNF
      treatment resulted in significant diminution of the levels of several individual
      and total I-compounds in liver at 48 h, but few effects were seen at the earlier
      time-points. Kidney I-compounds were also markedly affected by BNF at 48 h,
      albeit to a lesser extent than in liver. In both tissues, P450 induction preceded
      I-compound reduction. Taken together, the results of this investigation
      demonstrate significant diminution of I-compound levels by a single dose of BNF,
      a CYP1A1 inducer, in a time-dependent manner, suggesting the participation of a
      specific biochemical process, possibly involving CYP1A1, in the metabolic
      regulation of these endogenous DNA adducts.

PMID- 8560496
TI  - Evaluation of contact sensitivity to formaldehyde and tetramethylthiuram
      monosulfide using a modified lymphocyte transformation test.
AB  - To examine the validity of a modified lymphocyte transformation test for
      evaluating contact hypersensitivity from weak sensitizers, guinea pigs were
      sensitized with formaldehyde (F) or tetramethylthiuram monosulfide (TMTM) using
      the maximization test procedure. Lymph node cells from the animals were then
      cultured with F or TMTM, in the presence or absence of epidermal cells (EC).
      Transformed lymphocyte counts were evaluated by uptake of 3H-thymidine.
      Nonsensitized guinea pigs were used as controls. The lymphocytes from sensitized
      guinea pigs showed stronger blastogenesis when cultured with F or TMTM in the
      presence of EC than when the sensitizers were not added to the culture and the
      response depended on the concentration of F or TMTM. Cultures in the absence of
      EC also showed significant enhancement of blastogenesis by F or TMTM, but the
      responses were significantly weaker than those in the presence of EC. Lymphocytes
      from the control animals did not show significantly enhanced blastogenesis in
      response to F or TMTM, even when EC was added to the cultures. The results
      suggested that contact sensitivity for weak sensitizers can be evaluated by this
      modified lymphocyte transformation test, especially when lymph node cells were co
      cultured with EC.

PMID- 8560497
TI  - The effects of mercuric chloride on growth, cytokine and MHC class II gene
      expression in a human leukemic mast cell line.
AB  - We have examined the effects of mercuric chloride (HgCl2) on growth and IL-4, IL
      8, TNF-alpha and MHC class II gene expression in the HMC-1 human leukemic mast
      cell line. Proliferation, measured by [3H]thymidine incorporation or production
      of a formazan product (MTT assay), was substantially inhibited by HgCl2 at
      concentrations of 10(-6) M and above. Inspection of the DNA by agarose gel
      electrophoresis from HgCl2-treated cells revealed that it was intact, indicating
      inhibition of DNA synthesis, but not denaturation. HgCl2 inhibited expression of
      mRNA for IL-8, TNF-alpha and MHC class II at 4 x 10(-6) M and inhibited
      expression of IL-4 mRNA at 8 x 10(-6) M and above. At a concentration of 10(-5)M,
      HgCl2 almost completely blocked mRNA expression for IL-4, IL-8, TNF-alpha and MHC
      class II, but produced negligible inhibition of expression of mRNA encoding the
      housekeeping gene beta-actin, thus demonstrating selective toxicity for the
      cytokine and MHC class II genes studied. Pre-exposure of the cells to human
      recombinant IL-4 prior to treatment with HgCl2 had no effect on expression levels
      of any of the genes examined. The effects seen in this study are consistent with
      previous reports showing immunotoxic effects of HgCl2 on other cell types,
      therefore, the HMC-1 mast cell line may prove useful in further studies of mast
      cell cytokine gene expression and the mechanisms involved in cytokine gene
      toxicity.

PMID- 8560498
TI  - Effects of trichothecene structure on cytokine secretion and gene expression in
      murine CD4+ T-cells.
AB  - The effects of trichothecene structure on cytokine secretion and gene expression
      were assessed in primary CD4+ T-cells from murine spleen. CD4+ T-cells were
      stimulated with concanavalin A (Con A) for 2 or 7 days in the presence of various
      concentrations of the trichothecenes, vomitoxin (VT or deoxynivalenol), nivalenol
      (NIV), 15-acetyl deoxynivalenol (15-ADON), 3-acetyl deoxynivalenol (3-ADON), T-2
      toxin (T-2) and verrucarin A (Ver A). Culture supernatants were subsequently
      analyzed for interleukin (IL)-2, IL-4 and IL-5 by ELISA. At day 2, all
      trichothecenes were found to have inhibited production of IL-2, IL-4, and IL-5.
      However, at day 7, supernatant IL-2 was significantly increased (2-5.5-fold) in
      cultures containing VT, NIV, 3-ADON, and 15-ADON at 250, 250, 2500, and 1000
      ng/ml doses, respectively, when compared to control Con A-stimulated cultures;
      significant increases in IL-2 were not observed with T-2 and Ver-A. Similarly, at
      day 7, IL-4 and IL-5 were significantly increased in the presence of VT (100
      ng/ml), NIV (100 ng/ml), 3-ADON (1000 ng/ml), 15-ADON (500 ng/ml), T-2 (1 ng/ml),
      and Ver A (50 pg/ml, only IL-5) when compared to control cultures. IL production
      was inhibited at trichothecene concentrations exceeding the aforementioned
      optima. When total RNA of 2-day cultures was assessed by reverse transcriptase
      polymerase chain reaction (RT-PCR) in conjunction with Southern analysis, IL-2
      mRNA was also found to be superinduced by VT (50 and 100 ng/ml), NIV (50, 100 and
      250 ng/ml), 3-ADON (1500 ng/ml), 15-ADON (100 ng/ml), T-2 (0.5 ng/ml) and Ver A
      (25, 50 and 100 pg/ml); IL-4 mRNA by VT (50 ng/ml), NIV (50 ng/ml), and Ver A
      (25, 50 and 100 pg/ml); IL-5 mRNA by VT (50 ng/ml); and IL-6 mRNA by 15-ADON (100
      ng/ml) and Ver A (50 pg/ml). As the trichothecene concentration increased from
      these levels, inhibition of mRNA transcript levels was also observed for many of
      the interleukins. Taken together, the results suggest that trichothecenes as a
      group can either inhibit or superinduce both IL secretion and mRNA levels in CD4+
      T-cells. Superinduction exhibited a rank order of macrocyclic > type A > type B
      trichothecenes and was dependent on acylation of the trichothecene nucleus.

PMID- 8560499
TI  - Effect of several metallothionein inducers on oxidative stress defense mechanisms
      in rats.
AB  - One mechanism by which chemicals cause cellular injury is the formation of
      reactive oxygen species. In vitro studies have shown that metallothionein (MT), a
      small metal-binding, sulfhydryl-rich, readily inducible protein, can scavenge
      reactive oxygen species, especially hydroxyl radicals. Nevertheless, whether or
      not MT protects against oxidative stress in the intact animal is not known.
      Experimental induction of MT could help to clarify this question, however, it is
      unclear whether agents that induce MT also influence known antioxidant systems.
      Therefore, the present study was designed to determine whether the well-known MT
      inducers are specific for induction of MT or whether they might also influence
      other hepatic systems that protect against oxidative stress. Male rats were
      administered cadmium chloride (Cd; 30 mumol/kg, s.c.), zinc chloride (Zn; 1000
      mumol/kg, s.c.), alpha-hederin (alpha-H, 30 mumol/kg, s.c.) or lipopolysaccharide
      (LPS; 1 mg/kg, s.c.) 24 h prior to measurement of antioxidant systems. Zn and
      alpha-H increased hepatic GSH concentration 20% and 55%, respectively. Cd
      significantly increased, whereas LPS reduced, the activities of selenium
      dependent glutathione peroxidase and glutathione reductase. Glutathione S
      transferases were not altered by any of the inducers. Cd also increased DT
      diaphorase activity. Cd, Zn and alpha-H all decreased catalase activity 20-35%,
      while the activity of superoxide dismutase was unaffected by the inducers. The
      amount of total cytochrome P450 enzymes and cytochrome b5 were decreased by LPS,
      Cd and alpha-H, while Zn appeared to have no effect. The activities of P450
      enzymes towards testosterone oxidation were also decreased by LPS, Cd and alpha
      H. In conclusion, all four MT inducers examined affect systems known to protect
      cells against oxidative stress. Therefore, using these chemicals to determine the
      in vivo role of MT in protecting against oxidative stress poses difficulties.

PMID- 8560500
TI  - Sodium arsenite and heat shock induce stress proteins in precision-cut rat liver
      slices.
AB  - The present study was undertaken to investigate the usefulness of stress proteins
      as early, sensitive indicators of hepatotoxicity. Induction of stress protein
      synthesis in precision-cut rat liver slices was examined following in vitro
      exposure to sodium arsenite or heat shock. Precision-cut rat liver slices were
      incubated with 10(-5) or 10(-6) M sodium arsenite for 2, 4 or 8 h in the presence
      of 35S-methionine or exposed to hyperthermia (42.5 +/- 0.5 degrees C) for 45 min
      and then incubated with 35S-methionine for 2, 4 or 8 h. Fluorographic analysis
      indicated an increase in the synthesis of HSP 70 and HSP 90 family of proteins by
      both treatments. Immunoblot analysis demonstrated that there was a specific
      induction of HSP 72 and HSP 90. Induction of HSP 70 was greater than that of HSP
      90 by both treatments. Stress protein induction occurred at earlier times by
      concentrations of arsenite which did not alter other viability parameters such as
      leakage of intracellular K+ or total protein synthesis. The results indicated
      that induction of stress proteins has the potential usefulness as an early
      biomarker of arsenite toxicity.

PMID- 8560501
TI  - Compared toxicity of the potassium channel blockers, apamin and dendrotoxin.
AB  - The central toxicities of two potassium ion channel blockers, apamin and alpha
      dendrotoxin (DTx), have been compared. Both apamin and dendrotoxin injected
      intracerebroventricularly produced signs of poisoning, including tremor and
      ataxia; however, only DTx produced changes in brain electrical activity, with
      high voltage spikes and epileptiform activity and subsequent brain damage. DTx,
      but not apamin, increased the amplitude of evoked field potentials and caused
      repetitive firing of neurones in hippocampal slices. Signs of poisoning following
      peripheral (intraperitoneal) administration of apamin were similar to those
      following central administration, including dramatic haemorrhagic effects on the
      lungs of decedent animals. These results are consistent with dendrotoxin being a
      centrally-active neurotoxin producing epileptiform activity and brain damage,
      whilst apamin produces its most significant pathology in the lung, possibly
      involving a neurogenic mechanism.

PMID- 8560502
TI  - Comparison of rat hepatic and pulmonary microsomal metabolism of benzene and the
      lack of benzene-induced pneumotoxicity and hepatotoxicity.
AB  - Since little is known about the toxicity of benzene in the lung or if the lung is
      capable of metabolizing benzene, the ability of the lung to bioactivate or
      detoxify benzene and the pneumotoxicity of benzene were determined. While overall
      metabolism was lower, pulmonary microsomes converted benzene (17.5 microM) to
      hydroquinone, considered to be a marker for benzene toxicity, in proportionately
      greater amounts than did hepatic microsomes. Treatment of rats with pyridine, an
      inducer of CYP2E1, enhanced hepatic microsomal metabolism of benzene, although
      benzene, which is also considered to be an inducer of CYP2E1, did not. Neither
      pyridine nor benzene treatment induced the pulmonary microsomal metabolism of
      benzene. When hepatic and pulmonary microsomes from control and pyridine-treated
      rats were incubated with benzene (17.5 microM) and the CYP2E1 inhibitor,
      diethyldithiocarbamate, benzene metabolism was significantly inhibited,
      indicating that CYP2E1 is the predominant cytochrome P-450 isozyme involved in
      hepatic and pulmonary metabolism in microsomes from control and pyridine-treated
      rats. Benzene (600 mg/kg body weight, i.p.) did not cause significant lung cell
      damage as determined by measurement of gamma-glutamyltransferase and lactate
      dehydrogenase in bronchoalveolar lavage fluid. Induction of CYP2E1 and CYP2B1/2
      with pyridine and phenobarbital, respectively, did not alter this lack of effect.
      Thus, the primary concern about benzene and the lung should focus on benzene
      metabolism as opposed to acute toxicity.

PMID- 8560503
TI  - Effects of 1,2-dichloroethane intoxication on dolichol levels and
      glycosyltransferase activities in rat liver microsomes and Golgi apparatus.
AB  - Rat intoxication with a single dose of 1,2-dichloroethane (DCE) (50
      microliters/100 g b.w) is able to induce a significant modification of protein
      glycosylation in the liver endoplasmic reticulum and Golgi apparatus. HPLC
      analysis shows that within 5-60 min after DCE-intoxication, the levels of total
      dolichol, free dolichol and dolichyl phosphate strongly decreased in the
      microsomes and Golgi apparatus. Particularly in total microsomes, dolichyl
      phosphate, which is rate-limiting for the biosynthesis of the N-linked
      oligosaccharide chains, drops to values significantly lower than in the control
      group 15 min after DCE poisoning. In the Golgi apparatus, the total dolichol,
      essential to enhance the fluidity and permeability of these membranes, early and
      significantly decreases already 5 min after DCE poisoning. Moreover, in the Golgi
      apparatus galactosyl- and sialyltransferase activities, the main enzymatic
      activities of terminal protein glycosylation, are significantly reduced, as
      measured 15 min after DCE intoxication. These data suggest that the impairment of
      glycoprotein synthesis, maturation and secretion may be involved in the
      pathogenesis of liver injury induced by acute DCE-intoxication.

PMID- 8560505
TI  - Pathological changes in the Brown Norway rat cerebellum after mercury vapour
      exposure.
AB  - Our previous studies have demonstrated that mercury vapour exposure of Brown
      Norway rats induced an autoimmune response with development of glomerulonephritis
      and resulted in mercury deposition in the central nervous system, particularly in
      the neurons. The aim of this study was to investigate the effect on the central
      nervous system. A loss of Purkinje cells accompanied by Bergmann glial cell
      proliferation was found at a brain mercury level of 0.71 micrograms/g and became
      even more pronounced as the exposure dose increased. At a brain mercury level of
      5.0 micrograms/g, a heavy gliosis was present in the brain stem, particularly
      around the pontine nuclei. In comparison with our previous study, the
      pathological changes in the brain appeared at the same mercury exposure dose as
      the glomerulonephritis. However, the location of pathological changes at the
      mercury level of 0.71 micrograms/g was not completely in accordance with the
      mercury distribution in the brain, which might be due to the sequence of mercury
      deposition, its amount or the vulnerability of the various cells classes.

PMID- 8560504
TI  - Inhibition by phospholipids, lysophospholipids and gangliosides of melittin
      induced phosphorylation in bovine mammary gland.
AB  - Melittin, a toxic peptide from bee venom known to inhibit protein kinase C (PKC)
      activity, induces, like sphingosine, phosphorylation of proteins, such as the 19
      kDa and 27 kDa, in bovine mammary gland. This phosphorylation is inhibited by the
      addition of phosphatidylserine (PS). The present study was conducted to examine
      whether phospholipids (other than PS), lysophospholipids and gangliosides can
      inhibit the phosphorylation of cytosolic proteins from bovine mammary gland. The
      lipid effects were also explored in the sphingosine-induced phosphorylation for
      comparison. Like PS, phosphatidic acid, phosphatidylglycerol and
      phosphatidylinositol inhibited the melittin-induced phosphorylation.
      Phosphatidylcholine was less potent and phosphatidylethanolamine was inactive in
      inhibiting the phosphorylation. Similar results were obtained when sphingosine
      was used instead of melittin. Of the lysophospholipids tested, lysophosphatidic
      acid was most effective in inhibiting the phosphorylation induced by melittin.
      Lysophosphatidylcholine was inactive in reversing the melittin-induced
      phosphorylation, but it selectively suppressed the 19 kDa phosphorylation induced
      by sphingosine. Gangliosides inhibited both melittin- and sphingosine-induced
      phosphorylation and their effectiveness was: GT1b > GD1a = GD3 > GM3. Of the
      phosphoproteins, the 19 kDa was most sensitive to ganglioside inhibition. These
      results suggest that melittin-induced phosphorylation is selectively inhibited by
      specific lipids and also that the enzyme(s) responsible for the phosphorylation
      is not identical to the sphingosine-activated protein kinases.

PMID- 8560506
TI  - Potential metabolism and cytotoxicity of N-(3,5-dichlorophenyl)succinimide and
      its hepatic metabolites in isolated rat renal cortical tubule cells.
AB  - N-(3,5-Dichlorophenyl)succinimide (NDPS) is an agricultural fungicide and
      antimicrobial agent that produces nephrotoxicity in rats. The contribution of the
      kidney, if any, to the mechanism of toxicity of NDPS is not known. Therefore, the
      ability of isolated renal cortical tubule cells to metabolize NDPS and some of
      its known hepatic metabolites was studied. The cytotoxic potential of these
      compounds was also assessed. Renal cortical tubule cells were isolated by
      collagenase digestion and were incubated with the test compounds (2 mM) for 3 h.
      Metabolite formation was monitored by reversed phase HPLC and cell viability was
      assessed using trypan blue exclusion. The isolated kidney cells do not appear to
      metabolize NDPS or any of its known hepatic metabolites. In addition, none of
      these compounds were directly cytotoxic to the renal cells. However, the cells
      were susceptible to mercuric chloride (1 mM) and chloroform (125 or 200 mM).
      Intracellular glutathione levels were unaltered by the presence of NDPS in the
      incubations. These results suggest that NDPS and its metabolites are not directly
      toxic to the kidney and are not converted into the ultimate nephrotoxic species
      by the kidney. Extrarenal metabolism may, therefore, be critical to the
      expression of NDPS-induced nephrotoxicity.

PMID- 8560507
TI  - Adenosine triphosphate (ATP) levels in paracetamol-induced cell injury in the rat
      in vivo and in vitro.
AB  - We have investigated the relationship between ATP levels and the onset and
      progression of cell injury induced by paracetamol overdose both in vivo and in
      vitro. Liver slices obtained from phenobarbitone-induced and non-induced rats
      were used in a model in vitro system. Slices were exposed to paracetamol (2-10
      mM), for 120 min and then incubated without paracetamol for a further 240 min.
      ATP levels are reduced upon exposure to paracetamol in liver slices from both
      phenobarbitone-induced and non-induced rats. Cell injury, as quantified by
      measuring leakage of lactate dehydrogenase (LDH) and potassium (K+), does not
      become apparent until 240 min, some 120 min after exposure to paracetamol had
      ended. This irreversible cell injury is not observed in liver slices from non
      induced rats. For in vivo studies rats were phenobarbitone-induced and received
      i.p. injections of 800 mg/kg body weight paracetamol. Hepatic ATP levels were
      measured and are found to drop sharply by 3 h post-injection. Development of
      irreversible hepatic cell injury was assessed by measuring serum enzyme (ALT)
      activity. ALT levels do not rise until 12 h have elapsed. Paracetamol in overdose
      gives rise to ATP depletion in liver cells, that is early, independent of
      paracetamol metabolism and probably spread throughout the lobule. In contrast
      cell injury is found late and only in our phenobarbitone-induced rats. No cell
      injury is observed in liver slices from non-induced rats. This suggests that
      while the level of ATP depletion which is observed may be a necessary part of
      cell injury by paracetamol, it is not a sufficient cause.

PMID- 8560508
TI  - Induction of metallothionein in the Reuber H-35 rat hepatoma cell.
AB  - The feasibility of using the Reuber H-35 rat hepatoma cell (RH-35 cells) as model
      for studying metallothionein induction was examined. The RH-35 cells were treated
      with Cd, a toxic metal which is known to induce metallothionein. The LC50 after a
      3-h treatment was 70 microM. The value was significantly higher (P < 0.05) if the
      cells were pre-treated with a sublethal dose of CdCl2 (5 microM) for 2 days,
      indicating that pre-treatment with a low dose of Cd can protect against a
      subsequent higher dose of the same metal. Both the mRNA and the gene product
      metallothionein can be identified in the cells 2 days after treatment with 5
      microM Cd. In addition to Cd, Zn and Cu were also able to induce the expression
      of metallothionein to various degrees. The results indicate that the MT gene is
      present in RH-35 cells and is responsive to treatment with various metals. Thus,
      this cell line can be used as a model to study metallothionein induction.

PMID- 8560509
TI  - The Wellcome Tropical Medicine Resource: 19th century principles, 21st century
      technology, and distance learning with global horizons.

PMID- 8560510
TI  - Skin diseases of children in Mali: a public health problem.
AB  - In order to estimate the importance as a public health problem of skin diseases,
      we investigated the prevalence and severity of skin diseases in a representative
      sample of children in Mali. 1817 children were randomly selected in 30 clusters
      by probability-proportional-to-size sampling in Koulikoro region. The mean
      prevalence (+/- 2 SD) of skin diseases was 34 +/- 4%. The most frequent
      dermatoses were pyoderma (12.3 +/- 1.6%), tinea capitis (9.5 +/- 2.5%),
      pediculosis capitis (4.7 +/- 1.4%), scabies (4.3 +/- 1.5%), and molluscum
      contagiosum (3.6 +/- 1%). The most troublesome dermatoses were scabies and severe
      pyoderma. Pyoderma was the only dermatosis associated with poor individual or
      household hygiene. Public health services were little used by the population for
      skin diseases, probably because of the lack of an adequate response by the
      services and the high cost of treatment. The high prevalence and the severity of
      many of the lesions, and the discomfort caused, make pyoderma and scabies a
      significant public health problem in Mali.

PMID- 8560512
TI  - Cutaneous leishmaniasis of humans due to Leishmania (Viannia) naiffi outside
      Brazil.

PMID- 8560511
TI  - A prospective sero-epidemiological study of visceral leishmaniasis in Baringo
      District, Rift Valley Province, Kenya.
AB  - The incidence of visceral leishmaniasis (VL) was studied in 30 clusters with an
      average of 98 individuals in each cluster in a defined, endemic rural area of
      Baringo District, Kenya. The clusters were centred around recent cases of VL.
      Anti-leishmanial antibodies were measured by the direct agglutination test (DAT)
      and a clinical examination was performed on 2 occasions between April 1991 and
      May 1993. Of 2934 individuals tested by the DAT during the first visit, 78 (2.7%)
      were seropositive, 54 with and 24 without a history of VL. The seroconversion
      rate was 9/1000 person-years of observation (95% confidence interval 5.1-12.92)
      among 2332 seronegative individuals retested the following year. During the
      entire study period, VL was diagnosed in 10 patients, with an incidence rate of
      2.2/1000 person-years of observation (95% confidence interval 0.8-3.6). Household
      contacts of individuals with previously confirmed VL had a higher frequency of
      DAT positivity than the rest of the population. This difference was significant
      for both sexes. These results suggest transmission in and around houses.

PMID- 8560513
TI  - Anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: the high
      susceptibility of Phlebotomus sergenti to Leishmania tropica.

PMID- 8560514
TI  - High prevalence of Enterocytozoon bieneusi infections among HIV-positive
      individuals with persistent diarrhoea in Harare, Zimbabwe.
AB  - Infection with the microsporidian parasite Enterocytozoon bieneusi may be a major
      cause of prolonged diarrhoea in individuals also infected with human
      immunodeficiency virus (HIV). The parasite has been reported from Europe,
      Australia and the Americas, with a prevalence of 7-29%. Faecal specimens were
      obtained from 202 adults and 106 children in Harare, Zimbabwe, all of whom were
      in hospital and had diarrhoea. HIV serology was available for 119 adults: 106
      were HIV seropositive. There were clinical grounds for suspecting HIV infection
      in 23 of the remaining patients. E. bieneusi was identified in specimens from
      13/129 patients (10%) for whom HIV infection was indicated by serology and/or
      clinical signs, 1/60 patients (2%) of uncertain HIV status, and 0/13 seronegative
      patients. 18/106 children were HIV seropositive and 12 were not; HIV serology was
      not available for the remainder, but 19 were strongly suspected of being infected
      with HIV on clinical criteria. E. bieneusi was not detected in samples from any
      child. As is common in Zimbabwe, the prevalence of other parasites in faecal
      specimens was low and, amongst patients with proven or suspected HIV infection,
      E. bieneusi was the most prevalent parasite identified, particularly in patients
      with diarrhoea of over 4 weeks duration.

PMID- 8560515
TI  - Epidemiological aspects of hepatitis B and D virus infection in the northern
      region of Amazonas, Brazil.
AB  - The State of Amazonas in the Brazilian Amazon region is an area of high
      prevalence of hepatitis B and D virus (HBV and HDV) infection. The aim of this
      study was to identify epidemiological patterns and risk factors of HBV and HDV
      infections in Barcelos, in the basin of the Negro river. A random sample (798 in
      all) of the total population in the urban area and in 2 rural villages was
      surveyed. A standardized questionnaire was used and blood samples were tested by
      enzyme-linked immunosorbent assay: 1.63% had hepatitis B surface antigen, 12.9%
      had anti-hepatitis B surface antibody and 21.4% had anti-hepatitis B core
      antigen. The overall prevalence of HBV infection was 24.6%. Anti-hepatitis D was
      present in 5 subjects, all of them non-natives, and hepatitis B e antigen in 2. A
      positive association between history of dental treatment with an unqualified
      dental surgeon was found (P < 0.05). These results suggest a low prevalence of
      HVB and HDV infection, in contrast with other parts of the Amazon area.

PMID- 8560516
TI  - Prevalence of hepatitis C virus and other blood-borne viruses in Pygmies and
      neighbouring Bantus in southern Cameroon.
AB  - The prevalences of antibodies to hepatitis C virus (anti-HCV), human
      immunodeficiency virus (anti-HIV), human T lymphotrophic virus (anti-HTLV) and of
      hepatitis B surface antigen (HbsAg) were determined in 168 subjects aged 12 years
      and over (108 Pygmies, 60 Bantus) living in south Cameroon. In 167 subjects, we
      found an estimated minimal anti-HCV prevalence of 13%. The prevalence was
      significantly higher in Bantus (31.7%) than in Pygmies (11.1%) and increased with
      age in both groups, albeit more rapidly in Bantus. The overall prevalence of
      HBsAg was 7.2% and correlated with neither sex nor ethnic group. No association
      was found between anti-HCV and HbsAg prevalence rates. No subject was confirmed
      to be positive for HTLV or HIV. These findings confirm the high prevalence of HCV
      infection in south Cameroon and indicate that even secluded population groups are
      affected.

PMID- 8560517
TI  - Seroprevalence of hepatitis viruses in children in rural Viet Nam.

PMID- 8560518
TI  - Quantitative recovery of Burkholderia pseudomallei from soil in Thailand.
AB  - Melioidosis is common in north-eastern Thailand, but is reported rarely from the
      adjacent areas of central Thailand, although rice farming is common to both
      regions. Quantitative soil cultures for Burkholderia pseudomallei were therefore
      prepared on 12 rice farms in both regions. B. pseudomallei was isolated from a
      similar proportion of rice fields in the central region (6/12) and in the north
      east (7/12). Within the culture-positive sites, the number of B. pseudomallei
      colony-forming units (cfu) per mL of soil/water supernatant was significantly
      higher in the north-east (median 230 cfu/mL; range 1-17,000) than in the central
      region (median 10 cfu/mL; range 1-600). As bacterial counts in the soil are
      probably related to the risk of developing melioidosis, differences in exposure
      to B. pseudomallei probably contribute to the considerable differences in the
      incidence of this disease between these 2 adjacent regions.

PMID- 8560519
TI  - Survival of Burkholderia pseudomallei in the absence of nutrients.

PMID- 8560520
TI  - Visceral leishmaniasis: use of the polymerase chain reaction in an
      epidemiological study in Baringo District, Kenya.
AB  - The polymerase chain reaction was applied to capillary blood spots dried on
      filter paper from 20 parasitologically proved cases of visceral leishmaniasis
      (VL), 21 subclinical cases, and 11 healthy controls in a longitudinal study of
      anthroponotic VL in Baringo District, Kenya. Leishmania deoxyribonucleic acid
      (DNA) was detected 10.5 months before diagnosis and up to 3 years after diagnosis
      and apparently successful treatment. Subclinical cases can have detectable
      circulating parasite DNA in their blood. These findings may indicate that
      subclinical cases can be a reservoir and formerly treated VL patients can remain
      a reservoir for a long time. Xenodiagnosis should be performed on subclinical
      cases and former VL patients to establish their role in transmission of VL in
      Kenya.

PMID- 8560521
TI  - The value of an enzyme-linked immunosorbent assay for the diagnosis of
      schistosomiasis mansoni myeloradiculopathy.
AB  - The role of serological tests on cerebrospinal fluid (CSF) in the diagnosis of
      neuroschistosomiasis has not been fully elucidated; the condition is essentially
      diagnosed on the basis of circumstantial evidence, which may lead to an erroneous
      diagnosis, especially in highly endemic areas. We therefore carried out a
      prospective case-control study in which we compared the concentrations of
      immunoglobulin G (IgG) specific for schistosome soluble egg antigen (SEA) present
      in the CSF of 54 patients with schistosomiasis mansoni myeloradiculopathy (SMMR)
      with those observed in a control group consisting of 41 patients with
      epidemiological and serological evidence of exposure to schistosomes, and with
      other neurological disorders that result in mild to moderate impairment of the
      blood-brain barrier. Anti-SEA IgG was estimated by an enzyme-linked immunosorbent
      assay. The sensitivity, specificity and positive and negative predictive values
      were 56%, 95%, 94% and 62% respectively. Likelihood ratios and the corresponding
      post-test probabilities were determined for 4 levels of anti-SEA IgG in CSF. A
      value below 0.1 micrograms/mL practically excluded the possibility of SMMR (post
      test probability < 5%), a value above 1.4 micrograms/mL practically confirmed the
      diagnosis of SMMR (post-test probability > 96%), values of 0.1 to 0.5
      microgram/mL had no diagnostic value (post-test probability approximately 45%),
      and values of 0.6 to 1.4 micrograms/mL were useful in some situations (post-test
      probability approximately 70%). We conclude that the estimation of anti-SEA IgG
      in the CSF is useful for the diagnosis of SMMR.

PMID- 8560522
TI  - Transabdominal ultrasound for the diagnosis of Schistosoma haematobium infection
      of the upper female genital tract: a preliminary report.

PMID- 8560523
TI  - Helicobacter pylori in endoscopy patients in Zimbabwe: value of enzyme-linked
      immunosorbent assay and a rapid urease test.
AB  - Biopsy and serum specimens were obtained from 95 patients undergoing endoscopy at
      the University of Zimbabwe Medical School. Common presenting features were
      epigastric pain, bleeding and dyspepsia. Ulcers were detected in 16 patients
      (17%), and were more common in men (24%) than in women (7%). Histological
      examination of biopsies showed that all 95 patients had spiral-shaped organisms
      that were indistinguishable microscopically from Helicobacter pylori, though the
      numbers of organisms varied considerably. There was evidence that the degree of
      inflammation in the mucosa was related to the numbers of H. pylori-like organisms
      (HPLO) present. Fifty-one biopsy specimens (55%) gave a positive rapid urease
      test (RUT), with colour change occurring within 4 h. In all but one case, the
      gastric mucosa from these patients contained moderate to numerous HPLO. We
      defined the 'gold standard' of H. pylori-associated gastritis as the presence of
      both moderate to numerous HPLO and moderate to severe inflammation in the gastric
      mucosa. Using these criteria, RUT had a sensitivity of 67% and a specificity of
      68%. Sera from 92 patients were tested for immunoglobulin G antibodies reactive
      with a glycine-extract antigen of H. pylori, using an enzyme-linked immunosorbent
      assay (ELISA). Sera giving an indeterminate reaction in the ELISA were also
      tested by Western blotting. In all, 36 sera (39%) gave a positive ELISA or
      Western blot reaction. There was poor correlation between serology and RUT
      results, with only 57% of biopsy specimens from seropositive patients giving a
      positive RUT, compared with 45% from seronegative patients. Positive serology was
      found in only 35 patients (61%) with histological evidence of H. pylori
      associated gastritis, and the specificity of the test was only 54%. When used in
      combination with the RUT result, however, 79% of patients with a positive RUT and
      positive serology had histological evidence of H. pylori-associated gastritis.
      There was a general trend for increased seroprevalence in patients with mild to
      moderate atypia. These findings indicate that serology, using an antigen derived
      from the type strain of H. pylori, is unreliable in detecting H. pylori infection
      in Zimbabwe. Current studies are aimed at characterizing antigens from organisms
      isolated from Zimbabwean patients.

PMID- 8560524
TI  - Microbiological investigation of diarrhoea epidemics among Rwandan refugees in
      Zaire.

PMID- 8560525
TI  - Fever in uncomplicated Plasmodium falciparum malaria: randomized double-'blind'
      comparison of ibuprofen and paracetamol treatment.
AB  - Fever almost invariably accompanies uncomplicated falciparum malaria. In a
      randomized, double-'blind' study, we compared a single dose of ibuprofen (10
      mg/kg, n = 8) with paracetamol (15 mg/kg, n = 8) for the treatment of fever >
      38.5 degrees C due to uncomplicated falciparum malaria. Ibuprofen was
      significantly more effective than paracetamol in lowering temperatures throughout
      the first 4.5 h after dosing (P = 0.016) and should be considered as an
      antipyretic agent in the management of uncomplicated falciparum infections,
      providing there is no contraindication to its use.

PMID- 8560526
TI  - Multiple invasion of red blood cells by Plasmodium vivax in vivo.

PMID- 8560527
TI  - The effect of plasma free fatty acids and long-chain triglycerides on glucose
      metabolism in uncomplicated falciparum malaria.
AB  - To investigate the therapeutic potential of increased plasma free fatty acid
      (FFA) and triglyceride concentrations in hypoglycaemic patients receiving
      quinine, 32 untreated Thai adults with uncomplicated falciparum malaria were
      allocated at random to one of 4 regimens: 2 mg/kg/min dextrose infused over 60
      min either alone (group A) or with a prior injection of 5000 units of heparin and
      simultaneous Intralipid infusion (group C), or 4 min/kg/min dextrose alone (group
      B) or with heparin and Intralipid (group D). Quinine (10 mg/kg) was also infused
      over 60 min in all cases. In patients of groups A and C, mean changes in plasma
      glucose concentrations from the beginning to the end of the infusion were 0.1 (SD
      0.8) and 1.0 (SD 0.7) mmol/L respectively (P = 0.015). In groups B and D, plasma
      glucose increased by 1.8 (SD 1.2) and 2.2 (SD 0.4) mmol/L respectively (P < 0.5).
      Plasma FFA levels fell by approximately 50% during the infusion in groups A and B
      but increased by a similar percentage in groups C and D. Despite significant mean
      increases in plasma insulin during the infusion (from 12.2 milliunits (mu)/L in
      group A to 38.8 mu/L in group D), no rebound hypoglycaemia was observed in any
      patient during the ensuing 7 h. These data suggest that the glycaemic response to
      dextrose given at high rates, which match average glucose utilization in a
      severely ill patient with malaria, is not augmented by increased plasma FFA and
      long-chain triglycerides. However, this strategy increases the glycaemic efficacy
      of lower dextrose infusion rates and the combination could, therefore, reduce the
      volumes of hypertonic dextrose required to prevent hypoglycaemia in severely ill
      patients in whom optimal fluid balance is crucial.

PMID- 8560528
TI  - Co-existent kala-azar and malaria in India.

PMID- 8560529
TI  - Lymphatic pathology in Wuchereria bancrofti microfilaraemic infections.
AB  - To determine the extent of lymphatic disease in persons infected with Wuchereria
      bancrofti who were microfilaraemic, we examined the superficial lymphatics of the
      legs by scintigraphy. In 4 endemic control subjects and in 10 of 14 clinically
      asymptomatic microfilaraemic individuals, lymphoscintigraphy revealed one major
      channel of lymphatic drainage in each leg. However, while trunk lymphatics were
      bilaterally symmetrical in the control, marked differences in the calibre of
      lymphatic vessels were observed in the microfilaraemic persons. Non-discrete
      lymphatics and a diffuse symmetrical distribution of collateral vessels in both
      legs were observed in all of 5 amicrofilaraemic patients with grade 2
      lymphoedema. A similar diffuse drainage pattern was also seen in 3 previously
      microfilaraemic persons who had remained amicrofilaraemic and asymptomatic
      following treatment with diethylcarbamazine citrate (DEC). Thus, clearance of
      microfilaraemia by DEC therapy did not appear to reverse the type of lymphatic
      pathology observed in microfilaraemic subjects. The lymphoscintigraphy patterns
      did not correlate with serum levels of antibodies to 3 recombinant filarial
      antigens. Virtually all the asymptomatic microfilaraemic individuals infected
      with W. bancrofti examined had subclinical lymphatic disease detected by the non
      invasive imaging technique of lymphoscintigraphy.

PMID- 8560530
TI  - Hookworm infection in pregnancy.

PMID- 8560531
TI  - Artesunate versus artemether in combination with mefloquine for the treatment of
      multidrug-resistant falciparum malaria.
AB  - To compare the therapeutic efficacy of oral artesunate and artemether in
      combination with mefloquine for the treatment of multidrug resistant malaria, a
      trial was conducted in 540 adults and children on the Thai-Myanmar border. Three
      regimens were compared: artesunate (4 mg/kg/d for 3 d), artemether (4 mg/kg/d for
      3 d), both in combination with mefloquine (25 mg/kg), and a single dose of
      mefloquine (25 mg/kg). The artesunate and artemether regimens gave very similar
      clinical and parasitological responses, and were both very well tolerated. There
      was no significant adverse effect attributable to the artemisinin derivatives.
      Fever and parasite clearance times with mefloquine alone were significantly
      longer (P < 0.001). After adjusting for reinfections the failure rates were 13.9%
      for the artesunate combination, 12.3% for the artemether combination and 49.2%
      for mefloquine alone (P < 0.0001; relative risk 3.8 [95% confidence interval 2.6
      5.4]). Mefloquine should no longer be used alone for the treatment of multidrug
      resistant falciparum malaria in this area. Three-day combination regimens with
      artesunate or artemether are well tolerated and more effective.

PMID- 8560533
TI  - Successful treatment of experimental murine Trypanosoma brucei infection with
      topical melarsoprol gel.
AB  - Melarsoprol gel applied topically (0.1 mL for at least 2 d) can cure late-stage
      Trypanosoma brucei brucei and T. b. rhodesiense infections in mice. The best
      regimen was 3 applications at approximately 0, 6, and 24 h. The melarsoprol gel
      retained its activity at room temperature for at least 63 d. There was only
      minimal skin irritation and no sign of toxicity.

PMID- 8560532
TI  - Sensitivity of Plasmodium falciparum to amodiaquine and chloroquine in central
      Africa: a comparative study in vivo and in vitro.
AB  - A comparative study in vivo of amodiaquine efficacy (35 mg/kg over 3 d) and
      chloroquine (25 mg/kg over 3 d) was conducted in 1991 and 1992 in Cameroon and
      Congo in 123 patients with uncomplicated Plasmodium falciparum malaria.
      Amodiaquine was more effective than chloroquine, with parasite clearance by day 7
      in 79.7% of the patients compared with 59.4%. Sixteen of 32 (50%) P. falciparum
      isolates tested in vitro were resistant to chloroquine and only 3 of 34 (9%) were
      resistant to amodiaquine. 5.3% of patients treated with amodiaquine complained of
      pruritus and 18.7% of nausea, compared with 15.7% and 5% respectively of those
      treated with chloroquine.

PMID- 8560534
TI  - Low level ivermectin coverage and the transmission of onchocerciasis.
AB  - Regular collections of biting Simulium damnosum s.l. were carried out during a
      community-based trial of doses of ivermectin every 6 months for onchocerciasis in
      Sierra Leone. Over 64,000 blackflies were caught at 4 sites close to treated
      villages and one site near an untreated village. More than 17,000 of these
      blackflies were dissected during the 31 months of the study and 5 doses of
      ivermectin were distributed to about 30% of the human population in the treated
      villages. High annual biting rates (about 100,000 bites per year) and
      transmission potentials (about 5000 larvae per year) were found at all catching
      sites. Approximately 30% of parous blackflies carried Onchocerca volvulus larvae,
      and 8% had infective stage larvae. None of these indices appeared to be affected
      by the distribution of ivermectin. However, the mean number of larvae per
      infected blackfly fell from 8.7 to 5.8 during the study period in the treated
      villages, equivalent to a 21% decrease per year. No such reduction was seen in
      the control village. This study demonstrates that in areas where high capacity
      vectors predominate, the effect on transmission of even a low coverage of the
      human population with repeated doses of ivermectin may be detectable using the
      sensitive entomological index of intensity of infection in infected flies.
      Statistical analysis of onchocerciasis transmission data is a complex issue and
      ways of improving the design of trials and applying appropriate statistical
      methods are discussed.

PMID- 8560535
TI  - Rate of reinfection with intestinal nematodes after treatment of children with
      mebendazole or albendazole in a highly endemic area.
AB  - The comparative efficacy of albendazole and mebendazole in the treatment of
      intestinal nematode infections were compared 3 weeks after treatment in a
      randomized trial among schoolchildren on Pemba Island, Tanzania. Egg counts were
      compared 3 weeks, 4 months and 6 months after treatment of 731 children seen on
      each occasion. Differences in the efficacies were apparent with some nematodes 21
      d after treatment, but these were no longer apparent 4 months after treatment,
      and by 6 months intensities of infection were similar to pre-treatment levels.
      These findings suggest that treatment of schoolchildren every 4 months may be
      necessary in this highly endemic area in order to have an impact on the intensity
      of intestinal nematode infections sufficient to be likely to reduce morbidity.

PMID- 8560536
TI  - Immunological response to Vibrio cholerae O1 infection and an oral cholera
      vaccine among Peruvians.
AB  - A 'double-blind', randomized, placebo controlled study of an oral inactivated
      whole cell plus recombinant B subunit (WC/rBS) cholera vaccine was conducted
      during February-March 1992 in Peru in 346 military recruits, 307 (89%) of whom
      received 2 oral doses of vaccine or Escherichia coli K12 placebo, 2 weeks apart.
      Paired serum samples were obtained from 155 (50%) of the recipients of 2 doses.
      An epidemic of cholera took place between doses. No difference in cholera attack
      rates was detected between vaccine and placebo recipients after one dose (8%
      versus 14%). Seroconversion (4-fold or higher increase in vibriocidal antibody
      titres) was detected in 90% and 80% of vaccine and placebo recipients,
      respectively, with low pre-existing vibriocidal titres (< 0.01). The anti-cholera
      toxin seroconversion rate among those with low pre-existing titres was higher in
      vaccinated subjects (97%) than in placebo recipients (68%) (P < 0.01).
      Administration of 2 doses of WC/rBS vaccine concomitantly with natural V.
      cholerae O1 infection enhanced the serum anti-cholera toxin response. The immune
      response to the whole cell component of the vaccine was reduced by high pre
      existing vibriocidal antibody titres.

PMID- 8560537
TI  - A prospective comparison of co-amoxiclav and the combination of chloramphenicol,
      doxycycline, and co-trimoxazole for the oral maintenance treatment of
      melioidosis.
AB  - An open randomized comparison of the oral 'conventional' regimen (combination of
      chloramphenicol, cotrimoxazole and doxycycline) and co-amoxiclav for the
      maintenance treatment of melioidosis was conducted in Ubon Ratchatani, north
      eastern Thailand, between 1989 and 1992. The total antibiotic treatment duration
      was 20 weeks. Of 101 patients followed, 10 (10%; 95% confidence interval [CI] 4.9
      17.5%) subsequently relapsed: 2 of 52 patients (4%) in the oral 'conventional'
      group, and 8 of 49 patients (16%) receiving oral co-amoxiclav. This compares with
      a relapse rate of 23% in our previous study of 8 weeks' total therapy. Only 50%
      of patients complied with the 20 weeks' treatment regimen and poor compliance
      proved the most significant risk factor for subsequent relapse (relative risk
      [RR] 4.9, 95% CI 1.2-20.3). Neither the presence of known underlying disease nor
      choice of initial parenteral treatment was significantly associated with a higher
      risk of relapse. Co-amoxiclav is safer and better tolerated, but may be less
      effective (RR of relapse 0.4, 95% CI 0.2-1.2) than the oral 'conventional'
      regimen. The minimum duration of total treatment with either regimen should be 12
      20 weeks, depending on clinical progress.

PMID- 8560538
TI  - Treatment of snake bites by Bothrops species and Lachesis muta in Ecuador:
      laboratory screening of candidate antivenoms.
AB  - Bothrops xanthogrammus/asper, B. atrox and Lachesis muta are probably responsible
      for most cases of severe envenoming in Ecuador. In recent years, the most widely
      used antivenom ('Myn' Ronti, imported from Mexico) has proved clinically
      ineffective. There is an urgent need to identify an effective alternative for
      clinical testing. Five antivenoms with activity against Bothrops venoms were
      compared using standard World Health Organization rodent and in vitro assays: (i)
      'Myn', Ronti Mexico SA ('B. atrox', 'Crotalus terrificus'), (ii) Instituto
      Butantan (Bothrops polyvalent, Brazil), (iii) Instituto Nacional de Hygiene y
      Medicina Tropical (Bothrops polyvalent, Ecuador), (iv) Instituto Nacional de
      Salud (B. asper, C. durissus and Lachesis muta, Colombia), and (v) Laboratorios
      Probiol (Bothrops, Lachesis and Crotalus, Colombia). The venoms against which
      these antivenoms were tested were Ecuadorian B. atrox, B. asper and B.
      xanthogrammus. Brazilian antivenom proved to be the most effective, followed by
      the Ecudorian and Colombian antivenoms. Mexican antivenom was completely
      ineffective in neutralizing the lethal effects of Ecuadorian Bothrops venoms.
      Monospecific Brazilian L. muta antivenom (Instituto Butantan) proved effective
      against Ecuadorian L. muta venom, but the Colombian polyspecific antivenoms did
      not. Clinical trials of Brazilian and Ecuadorian antivenoms are planned in the
      Amazon region of Ecuador in the near future.

PMID- 8560539
TI  - Acquired antibody levels to Plasmodium falciparum merozoite surface antigen 1 in
      residents of a highly endemic area of Papua New Guinea.
AB  - The prevalence and concentration of antibodies to a yeast-expressed N-terminal
      region (195A) and a baculo-virus-expressed C-terminal region (BVp42) of merozoite
      surface antigen 1 (MSA-1) were measured during a cross-sectional survey in the
      Wosera area of East Sepik Province, Papua New Guinea, in order to obtain baseline
      data on naturally acquired antibody response to this antigen in preparation for a
      vaccine trial. Overall, the seropositivity rate was 78% for 195A and 91% for
      BVp42. Although antibody prevalence to both molecules increased with age, higher
      antibody prevalence rates were observed for BVp42 in all age groups studied. In
      children, significant positive associations were found between parasite
      prevalence and antibody prevalence for both regions of MSA-1 and between spleen
      rates and anti-BVp42 antibody prevalence. Concentration of antibody against both
      regions increased significantly with age, but was always higher for BVp42. In
      children, antibody levels to both regions of MSA-1 were significantly higher in
      those infected (symptomatic and asymptomatic), while in adults no significant
      difference in antibody concentration was observed between those infected and
      those uninfected. However, enlarged spleens were associated with higher antibody
      concentration to both regions of MSA-1 in both children and adults. The C
      terminal of MSA-1 appeared to be more recognized than the N-terminal, in terms of
      both antibody prevalence and concentration.

PMID- 8560540
TI  - A longitudinal study of malaria infection, morbidity and antibody titres in
      infants of a rural community in Ghana.

PMID- 8560541
TI  - Nutritional status and the IgE response against Ascaris lumbricoides in children
      from a tropical slum.
AB  - Helminthic infection can stimulate the interleukin-4 (IL-4)-dependent polyclonal
      synthesis of immunoglobulin E (IgE) in children endemically exposed to these
      parasites. As such children are also frequently at nutritional risk, in this
      study we considered the possible influence of malnutrition on serum IL-4 levels
      and the IgE response in helminthic infection. We evaluated 85 Ascaris-infected
      children living in an urban slum area of Caracas, Venezuela, and found that the
      serum levels of IL-4 and total IgE were significantly higher in malnourished
      children than in their well nourished counterparts. In contrast, the specific
      anti-Ascaris IgE antibody response was significantly lower in the malnourished
      group. After anthelmintic treatment of the children, the total serum IgE and IL-4
      levels decreased significantly in the well nourished group, while the specific
      anti-Ascaris IgE antibody response increased. No significant change was detected,
      however, in the malnourished group. Our results suggested that malnutrition
      potentiates the polyclonal stimulation of IgE synthesis induced by helminths. As
      specific IgE antibody has been implicated in the resistance to helminthic
      infection, and the polyclonal stimulus diminishes this response, these factors
      may increase the susceptibility of malnourished children to such parasites.

PMID- 8560542
TI  - Isolation and partial characterization of a Paracoccidioides brasiliensis 58 kDa
      extracellular glycoprotein which is recognized by human immune sera.
AB  - A novel 58 kDa antigenic determinant of the fungus Paracoccidioides brasiliensis
      was identified by enzyme-linked immunosorbent assay using a panel of species
      specific murine monoclonal antibodies (MAbs). Western immunoblot analysis,
      deglycosylation studies and isoelectric focusing indicated that this 58 kDa
      antigen is a glycoprotein, with a pI of approximately 5.2. The molecule was
      purified from P. brasiliensis culture filtrate and yeast cytoplasmic antigens by
      membrane ultrafiltration, liquid isoelectric focusing and gel filtration; N
      terminal amino acid sequence data revealed no substantial homology with known
      proteins. The presence of the antigen in the cytoplasm of both yeast and mycelial
      forms of the fungus was demonstrated when these MAbs were used as markers in
      immunofluorescence, immunoperoxidase and immunoalkaline phosphatase techniques to
      label P. brasiliensis in cryostat sections. These MAbs also recognized the
      cytoplasm of P. brasiliensis yeast forms in paraffin-embedded pathological
      specimens from human cases. A preparation of the 58 kDa component from yeast
      cytoplasmic antigen was reacted by Western immunoblotting with 26 different serum
      samples from paracoccidioidomycosis patients, and 81% of them recognized it.

PMID- 8560543
TI  - Syndrome resembling tropical pulmonary eosinophilia but of non-filarial
      aetiology: serological findings with filarial antigens.
AB  - Although the tropical pulmonary eosinophilia (TPE) syndrome of filarial aetiology
      has very distinctive clinical and immunological features, its clinical profile is
      not unique; other helminths sometimes induce similar presentations. We carefully
      evaluated 7 individuals with non-filarial TPE-like syndromes and found that
      serological tests based on detection of 'antifilarial' immunoglobulin (Ig) G,
      IgG4, and IgE antibodies that are usually considered diagnostic for filarial TPE
      were equally elevated in patients with non-filarial, TPE-like syndromes and were
      therefore unhelpful diagnostically. The apparent reasons were immunological hyper
      responsiveness of such individuals and the shared (i.e., cross-reactive)
      antigenicity found in the filarial antigen preparations used routinely for
      diagnosis. Because appropriate treatment for those different pulmonary
      eosinophilia conditions requires different drugs and management, and because
      delay in effective treatment results in significant morbidity in such patients,
      diagnostic capabilities must be improved by identifying and obtaining unique
      antigens that can serologically discriminate between filarial TPE and other
      similar, but non-filarial, pulmonary eosinophilia syndromes.

PMID- 8560544
TI  - Change in the type of wild poliovirus circulating in the Central African Republic
      between 1991 and 1994.

PMID- 8560545
TI  - Immediate detection of malaria parasites by acridine orange staining.

PMID- 8560546
TI  - Multilineage hematopoietic reconstitution of supralethally irradiated rats by
      syngeneic whole organ transplantation. With oarticular reference to the liver.

PMID- 8560547
TI  - Effect of monoclonal anti-CD4 and anti-CD8 on skin allograft survival in mice
      treated with donor bone marrow cells.
AB  - Allograft unresponsiveness can be induced by donor bone marrow cells (BMC) in
      antilymphocyte serum (ALS)-treated recipients. The effect of administering
      monoclonal anti-CD4 and -CD8 at several points has been examined in a mouse skin
      allograft model of this protocol. Brief peritransplant administration of anti-CD4
      and -CD8 was used to replace ALS. Anti-CD4 treatment prolonged graft survival
      only slightly and conditioned recipients poorly for the effect of
      posttransplantation donor BMC infusion. Anti-CD8 was ineffective in both
      capacities. A mixture of anti-CD4 and anti-CD8 was at least as effective as ALS
      in prolonging graft survival and in promoting the beneficial effects of donor
      BMC. Like the monoclonal antibodies, ALS also depleted splenic and lymph node
      CD4+ and CD8+ cells. Injection of ALS, but not the monoclonal antibodies, altered
      the CD4/CD8 phenotype of thymocytes, although persistent binding of both types of
      antibody to thymocytes was demonstrated. Abrogation of the positive effect of BMC
      by reconstitution of normal spleen cells on day +3 after ALS treatment confirmed
      that cell depletion is a requirement of this system. Monoclonal antibodies were
      also given to ALS/BMC-treated recipients after their grafts had become
      established. Anti-CD8 injection at either 2 or 4 weeks after transplantation
      further prolonged graft survival. In contrast, anti-CD4 injection at 2 or 6 weeks
      after grafting precipitated rejection, which suggests that continued allograft
      survival following ALS and donor BMC treatment is due to the activity of a CD4+
      cell population.

PMID- 8560548
TI  - Association between epidermal interleukin-10 secretion and the ability of
      cotransplanted skin from neonatal donors to prolong adult allograft survival.
AB  - Cotransplantation of skin from neonatal donors prolongs the survival of adult
      skin allografts on rabbit anti-mouse lymphocyte serum-treated and donor bone
      marrow cell-treated mice relative to controls (the cotransplant effect). In B6AF1
      (H2a/b) recipients, cotransplants of skin from C3HeB/FeJ (C3H; H2k) neonates up
      to 6-7 days old prolonged the survival of adult C3H skin grafts. Skin from 9- to
      10-day-old neonates was inactive. The magnitude of the cotransplant effect
      declined with increasing cotransplant age. Although few class II+ cells are
      present in skin from < 24-hr-old mice, the numbers of these cells increase
      rapidly after birth. On days 3-4, when the cotransplant effect is strong, their
      numbers in neonatal skin are greater than in adult skin. Development of class II
      expression continues when neonatal skin is grafted, but with an apparent 2-day
      lag. Because class II+ cell numbers decline in grafted adult skin, we speculate
      that this apparent developmental lag may be due to Langerhans cells migrating
      from the graft as they mature. Epidermal cells from litters of neonates were
      cultured overnight and supernatants were tested for interleukin (IL)-10. All 11
      samples from 0- to 4-day-old neonates and 4 of 9 samples from 4- to 7-day-old
      neonates were positive. IL-10 was found in 1 of 9 samples from donors 8-16 days
      old and 1 of 7 samples from individual adult mice. Thus, there is a temporal
      association between the ability of neonatal skin to produce a cotransplant effect
      and its ability to secrete IL-10.

PMID- 8560549
TI  - Donor-specific prolongation of rat skin graft survival induced by rat-donor cells
      and cyclophosphamide under coadministration of monoclonal antibodies against T
      cell receptor alpha beta and natural killer cells in mice.
AB  - Because of the recent interest in human xenotransplantation, we investigated the
      possibility of inducing tolerance in a xenogeneic combination using
      cyclophosphamide (CP). Donor-specific prolongation of xenogeneic Fisher 344
      (F344) rat skin graft survival for up to 60 days was induced in C57BL/6 (B6) mice
      by giving F344 bone marrow cells and spleen cells on day 0, CP on day 2, and
      monoclonal antibodies against murine TCR-alpha beta and NK1.1 on days--1 and 3.
      The inoculation of the xenogeneic cells brought accelerated repopulation of TCR
      alpha beta+ T cells, even under the administration of anti-TCR-alpha beta mAb.
      The quick increase of the host TCR-alpha beta+ T cells caused by the xenogeneic
      cell injection was deeply suppressed by CP. Mixed lymphocyte reaction, CTL
      activity, and antibody production against donor F344 were profoundly suppressed
      for 50 days. Mixed xenogeneic chimerism was observed for 1 month after the
      inoculation of donor cells in the spleen and peripheral blood of the recipient B6
      mice, but was never observed in the thymus. Moreover, when irradiated F344 cells
      were used in place of viable cells, chimerism was never detected and graft
      survival was only slightly prolonged. Clonal deletion of V beta 5- or V beta 11
      bearing murine T cells was not observed on day 50 in the thymus or spleen of the
      recipient B6 mice. These results suggest that treatment with viable xenogeneic
      donor cells, CP, and mAbs against T and NK cells can induce a temporary
      peripheral mixed chimerism and donor-specific prolongation of xenogeneic skin
      graft survival. The destruction with CP of T and B cells that are xenoreactive
      and thus proliferating after antigen stimulation, followed by mechanism other
      than intrathymic clonal deletion, may be the mechanism of the hyporesponsiveness
      in the present system.

PMID- 8560550
TI  - Natural killer cells weakly resist engraftment of allogeneic, long-term,
      multilineage-repopulating hematopoietic stem cells.
AB  - Natural killer (NK) cells effect hybrid resistance, in which parental
      hematopoietic cell grafts are rejected by F1 recipients. NK cells can also resist
      engraftment of fully MHC-mismatched allogeneic marrow. However, studies of NK
      cell-mediated alloresistance have relied on short-term proliferation, colony, or
      survival assays; therefore, their results may not reflect effects of NK cells on
      the engraftment of allogeneic pluripotent hematopoietic stem cells (PHSC). We
      have now addressed the role of NK cells in resisting engraftment of these most
      primitive hematopoietic cells, which provide long-term repopulation of multiple
      hematopoietic lineages. We took advantage of a nonmyeloablative conditioning
      regimen that permits allogeneic marrow engraftment and induction of mixed
      chimerism in mice to evaluate the effect of host NK cell depletion with mAb PK136
      on long-term competitive repopulating ability of allogeneic marrow. Mice were
      pretreated with depleting anti-CD4 and anti-CD8 mAbs, then received 3 Gy of whole
      body irradiation and 7 Gy of thymic irradiation prior to allogeneic bone marrow
      transplantation. Depending on the strain combination used, statistically
      significant increases in long-term allogeneic repopulation of both myeloid and
      lymphoid cell lineages were observed in recipients depleted of NK cells before
      bone marrow transplantation compared with controls. Depletion of host NK cells
      alone was sufficient to enhance donor PHSC engraftment. However, a statistically
      significant increase in allogeneic reconstitution in NK cell-depleted chimeras
      compared with control chimeras was not observed in every experiment, and
      differences were most readily apparent in a strain combination in which recipient
      NK cells have been shown to have high resistance to engraftment of donor short
      term repopulating cells. Chronic (16 weeks) anti-NK1.1 treatment resulted in
      higher levels of donor-type repopulation than that in animals receiving only
      pretransplant NK cell depletion. Our studies demonstrate for the first time that
      host NK cells resist engraftment of allogeneic long-term repopulating PHSC, and
      provide a model for studying the elements that determine what is regarded as
      "self" and "non-self" by newly developing NK cells.

PMID- 8560551
TI  - The alpha-1,3-galactosyltransferase knockout mouse. Implications for
      xenotransplantation.
AB  - Organ xenografts in discordant combinations such as pig-to-man undergo hyperacute
      rejection due to the presence of naturally occurring human anti-pig
      xenoantibodies. The galactose alpha(1,3)-galactose epitope on glycolipids and
      glycoproteins is the major porcine xenoantigen recognized by these
      xenoantibodies. This epitope is formed by alpha(1,3)-galactosyltransferase, which
      is present in all mammals except man, apes, and Old World monkeys. We have
      generated mice lacking this major xenoantigen by inactivating the alpha(1,3)
      galactosyltransferase gene. These mice are viable and have normal organs but
      develop cataracts. Substantially less xenoantibody from human serum binds to
      cells and tissues of these mice compared with normal mice. Similarly, there is
      less activation of human complement on cells from mice lacking the galactose
      alpha(1,3)-galactose epitope. These mice confirm the importance of the galactose
      alpha(1,3)-galactose epitope in human xenoreactivity and the logic of continuing
      efforts to generate pigs that lack this epitope as a source of donor organs.

PMID- 8560552
TI  - Restricted TCR V beta repertoire in the human mixed lymphocyte reaction is
      determined by the TCR on the responder cell and not by the stimulating antigen on
      the stimulator cell.
AB  - The use of a restricted TCR repertoire has been reported in antigen-stimulated T
      cells. We have examined by flow cytometry and polymerase chain reaction the
      changes in the TCR variable beta (V beta) repertoire as they occur in the mixed
      leukocyte reaction. The HLA class I-negative lymphoblastoid B cell line, Daudi,
      an HLA class I-positive variant of the Daudi cell line, and the homozygous typing
      cell line HTC 9062 were used to stimulate HLA-mismatched responder cells from 8
      individuals. The magnitude of HLA incompatibility in various combinations ranged
      from single DR10 and DR13 differences to full 6-antigen differences at the HLA-A,
      -B, and -DR loci. Using a panel of 19 V beta-specific oligonucleotide primers,
      changes in the level of TCR V beta mRNA were assessed. The observed V beta
      repertoire was not specific for the stimulator cell antigens used. We did not
      find a correlation between the number of mismatched HLA antigens and the number
      of V beta elements involved. It rather appeared that individual responder cells
      displayed a uniform V beta pattern following exposure to single and multiple HLA
      antigens. We conclude that the V beta repertoire was largely determined by
      factors associated with the TCR on the responder cells, and not as obviously
      influenced by the HLA antigen(s) on the stimulator cells.

PMID- 8560553
TI  - Effects of leflunomide and other immunosuppressive agents on T cell proliferation
      in vitro.
AB  - Leflunomide and its active metabolite, A771726, are structurally unrelated to
      immunosuppressive agents currently under investigation. Previous in vitro studies
      have revealed that leflunomide primarily inhibits interleukin-2-stimulated T cell
      proliferation. In the current study, we have extended our previous work and
      demonstrate that leflunomide prevents T cell progression induced by
      phytohemagglutinin into the S phase of the cell cycle. To discriminate further
      the action on T cells of leflunomide from other immunosuppressive agents, we
      performed kinetic studies where leflunomide was added either after the initiation
      of mixed lymphocyte cultures (MLC) or after interleukin-2 stimulation of CTLL-4
      cell proliferation. These studies revealed that leflunomide acted comparably to
      rapamycin, but was distinct from brequinar sodium in the MLC, and from
      cyclosporine and mycophenolic acid in both MLC and CTLL-4. Although previous
      biochemical studies indicated that leflunomide can inhibit src-family tyrosine
      kinase activity, more recent studies have suggested that leflunomide can also
      inhibit pyrimidine synthesis. Our data demonstrate that the ability of
      leflunomide (25-100 microM) to inhibit MLC and CTLL-4 cell proliferation is
      partially antagonized by uridine (25-100 microM), and support the hypothesis that
      leflunomide inhibits pyrimidine synthesis in T cells. Unique molecular mechanisms
      of immunosuppression suggest that drug combinations may result in synergistic
      immunosuppression. Our in vitro studies revealed synergistic inhibition of T cell
      proliferation with the combinations of leflunomide with cyclosporine or with
      rapamycin. We have extended those studies to quantitate inhibition of MLC by the
      combinations of leflunomide and brequinar sodium or mycophenolic acid.

PMID- 8560554
TI  - Cryptococcal meningitis after liver transplantation.
AB  - We present our experience with 10 liver transplant recipients in whom
      cryptococcal meningitis developed after liver transplantation. Disease developed
      a median period of 3.5 months (range, 2-36 months) after transplantation and
      patients were diagnosed a median period of 9 days (range, 2-90 days) after
      initial symptoms. Headache, fever, and mental status changes were the most
      frequent clinical presentations, while meningismus was found in only 30% of
      patients. Cerebrospinal fluid analysis was diagnostic in all cases. All patients
      were treated with amphotericin B and flucytosine. Immunosuppression was either
      decreased or discontinued during therapy. Five patients died, four as a direct
      result of cryptococcal infection and one as a result of chronic rejection. Three
      patients had long-term survival without any sequelae. One long-term survivor
      suffered blindness consequent to the disease. We conclude that cryptococcal
      meningitis is a rare complication in liver transplant recipients (0.25%), and has
      a high mortality rate (50%). Early recognition, combination antifungal therapy,
      and decrease or discontinuation of immunosuppression are important for cure. No
      relapse has been seen in surviving patients.

PMID- 8560555
TI  - Rhesus immunization after renal transplantation.
AB  - Previous reports, before the advent of cyclosporine, suggest that the small
      amount of blood transplanted with a kidney can result in rhesus D (RhD) antibody
      production. We looked for retrospective and current evidence of primary RhD
      antibody production following renal transplantation in RhD-negative recipients of
      an RhD-positive kidney. Of 42 patients, all on triple immunosuppressive therapy,
      2 (5%) were found to have an RhD antibody identified for the first time after
      transplantation. As the number of pregnancies in transplant recipients increases,
      the small risk of primary immunization and subsequent risk of hemolytic disease
      of the newborn will become more important. Therefore, we recommend that all RhD
      negative women of child-bearing age receiving an RhD-positive solid organ
      transplant are given a prophylactic dose of 500 IU of anti-D immunoglobulin
      intramuscularly at the time of transplantation.

PMID- 8560556
TI  - HLA matching in pediatric recipients of a first kidney graft. A single center
      analysis.
AB  - We retrospectively examined the effect of HLA-A, -B, and -DR serological matching
      on graft survival in 88 pediatric end-stage renal disease patients who underwent
      primary renal transplantation. Actuarial graft survivals (GS) at 2 and 6 years in
      patients with zero DR mismatches (MM) (12 patients) or 1 DR MM (58 patients) were
      significantly higher than those in patients with 2 DR MM (18 patients) (2-year
      GS: 100% vs. 90% vs. 59%; 6-year GS: 100% vs. 79% vs. 59%, respectively). Because
      of the low number of patients in the zero DR MM group, only the GS difference
      between 1 DR MM and 2 DR MM had a significant result at 1 year (92% vs. 68%). No
      clear HLA matching effect was obtained in the HLA-A and -B loci. When DR were
      combined with A or B antigens (0-2 MM vs. 3-4 MM), significantly higher GS at 1,
      2, and 6 years persisted for patients with 0-2 MM only in the A, DR group (96%,
      94%, and 85% vs. 68%, 63%, and 56%, respectively). It is suggested that avoidance
      of mismatching for DR alleles at the serological level, in the selection of
      pediatric recipients of first cadaveric renal transplantation, leads to an
      improvement of both short- and longterm graft outcome.

PMID- 8560557
TI  - Radionuclide studies in intestinal transplantation. Diagnosis of rejection and
      assessment of permeability.
AB  - Three patients who received intestinal allografts were studied using two distinct
      radionuclide investigations. In the first, 111In or 99mTc-labeled leukocyte
      scanning was performed to assist in the diagnosis of rejection. It was able to
      demonstrate the occurrence of rejection in the transplanted intestine, and the
      response to antirejection therapy. In 1 case, the abnormality on the scan
      preceded the histological confirmation of rejection. The second technique studied
      mucosal integrity by serial 51Cr-EDTA/14C-mannitol permeability tests. These
      studies demonstrated the initial marked impairment and the slow return to normal
      function of the intestinal mucosal barrier. In 1 patient, this occurred by 91
      days; in another, it took 232 days. A single assay performed in the third patient
      at the time of allograft rejection was also abnormal. Both radionuclide tests
      were helpful in the care of these complicated cases.

PMID- 8560558
TI  - Cyclosporine inhibition of leukocyte calcineurin is much less in whole blood than
      in culture medium.
AB  - Recent reports have shown that cyclosporine (CsA)-treated patients have abundant
      calcineurin phosphatase (CN) activity in vivo despite CsA blood concentrations
      that would be completely inhibitory in vitro. We sought to determine whether this
      disparity was a result of altered distribution of CsA in culture medium (CM)
      compared with whole blood (WB). CN activity was measured in peripheral blood
      leukocytes (PBL) that had been exposed in vitro to CsA in either WB or CM. Cells
      from both groups were also stimulated with OKT3 to determine the effect of CsA on
      the induction of IFN-gamma synthesis. CsA accumulation in PBL was determined by
      liquid scintillation counting of PBL exposed to 3H-CsA. The IC50 for CsA
      inhibition of CN activity was significantly lower for PBL in CM (2 micrograms/L)
      compared with PBL in WB (102 micrograms/L, P < or = 0.005). Likewise, for CsA
      inhibition of IFN-gamma induction, the IC50 was 18 micrograms/L for PBL in CM
      compared with 690 micrograms/L for PBL in WB (P < or = 0.005). The shift in IC50
      was accompanied by a 10-fold increase in 3H-CsA in PBL in CM compared with PBL in
      WB. We conclude that PBL exposed to CsA in CM accumulate significantly more CsA
      than PBL in WB. The result is that CsA inhibition of CN activity and cytokine
      induction appears at least an order of magnitude greater than its true effect in
      biologic fluids. This disparity is due to partitioning of CsA to irrelevant CsA
      binding sites, which are abundant in WB and in vivo, but absent in culture
      medium.

PMID- 8560559
TI  - Human natural killer cells induce morphologic changes in porcine endothelial cell
      monolayers.
AB  - In this study, we have investigated the early in vitro effects of natural killer
      (NK) cells on porcine aortic endothelial cell (PAEC) monolayers. Incubation of
      effector cells containing about 70% CD56+ cells on PAEC monolayer led to time
      dependent changes in PAEC monolayer morphology. As little as 20 min of incubation
      resulted in changes in PAEC shape and in the appearance of gaps between the
      cells. These effects have been observed for up to 6 hr, but not before 20 min or
      after 6 hr. When NK-depleted effector cells were used, no morphological changes
      were observed in comparison with the same effectors before depletion; if CD56+
      cells were added back, the effects were comparable with those on nondepleted
      effector cells. There was no detectable NK cell-mediated cytolytic activity
      during the 1-6 hr of incubation of peripheral blood lymphocytes with PAEC
      monolayers. These data indicate that NK cells may participate in endothelial cell
      changes leading to xenograft rejection.

PMID- 8560560
TI  - Peripheral monitoring of direct and indirect alloantigen presentation pathways in
      clinical heart transplant recipients.
AB  - It has been reported that the response to alloantigens presented by the direct
      and indirect pathway may be of differential relevance after human kidney
      transplantation. Accordingly, we monitored these routes in peripheral blood
      mononuclear cells (PBMC) of heart transplant patients from before transplantation
      and up to 2 years thereafter in an attempt to find a correlation with the
      clinical status of the patients. Both before and after transplantation,
      comparable proportions of PBMC samples reacted in mixed lymphocyte culture to
      nondepleted donor spleen cells (direct route), but never to donor cells depleted
      for antigen-presenting cells (indirect route). In contrast, the latter route
      could easily be activated by a nominal antigen and persisted after
      transplantation, although the proportion of PBMC samples responding was
      significantly suppressed, irrespective of the occurrence of rejection.
      Consequently, complete removal of antigen-presenting cells from the stimulator
      population in a mixed lymphocyte culture with PBMC as responder is not a suitable
      tool for measuring indirect presentation of alloantigens, and therefore not
      relevant for monitoring the immunological status of heart transplant recipients.

PMID- 8560561
TI  - Apoptosis as a mechanism of cell death in liver allograft rejection.

PMID- 8560562
TI  - Detection of anti-idiotypic antibodies after OKT3 treatment by flow cytometry.

PMID- 8560563
TI  - Donor-recipient microchimerism and tolerance induction.

PMID- 8560564
TI  - The use of N-acetylcysteine in solid-organ preservation solutions.

PMID- 8560565
TI  - Low dose isotretinoin in the prophylaxis of skin cancer in renal transplant
      patients.

PMID- 8560566
TI  - Synthesis of high energy phosphates during cold ischemic rat liver preservation
      with gaseous oxygen insufflation.
AB  - The depletion of biochemical energy stores during anoxic ischemic preservation is
      a major problem affecting the viability of the graft in transplantation medicine.
      After cessation of blood flow and, thus, lack of metabolic substrates and oxygen
      supply, a swift decrease of energy-rich phosphates can be observed in the tissue,
      since endergonic metabolic processes continue, but no further oxidative
      regeneration of biochemical energy stores will take place. We investigated the
      effect of a continuous gaseous oxygen supply via the venous vessels during
      extended ischemic preservation of rat livers in University of Wisconsin
      preservation solution for 48 hr. Results showed that aerobic ischemic storage not
      only prevented the depletion of biochemical energy stores, but promoted a de novo
      synthesis of high energy phosphates, and significantly enhanced the functional
      recovery of the organs after postischemic reperfusion. The findings suggest that
      maintenance of oxidative energy metabolism largely protects the organ during
      ischemia and may enable organ viability even after extended preservation times.

PMID- 8560567
TI  - Influence of pulmonary arterial pressure during flushing on lung preservation.
AB  - The effect of changing pulmonary artery pressure during flushing (flushing
      pressure) on lung preservation was examined in an ex vivo rabbit lung perfusion
      model. Both lungs were flushed in situ with 200 ml of a preservation solution
      (extracellular fluid [ECF] type) at 8 degrees C, at a constant flushing pressure
      maintained by regulating the flushing flow rate from 20 to 120 ml/min. In the
      controls, the flushing pressure was maintained at 15 mmHg and the lungs were
      assessed without storage. In the other 5 groups (n = 7 in each group), the lungs
      were flushed at pressures of 5, 10, 15, 20, and 25 mmHg, respectively. The heart
      lung block was then harvested, and immersed in the same solution at 8 degrees C
      for 24 hr. After 24 hr of storage, the block was reperfused with pooled venous
      blood for 10 min, and then with oxygenated blood for another 60 min in a closed
      circuit. Assessment of lung function included blood gas analysis of effluent
      blood, pulmonary artery pressure, airway pressure, wet:dry weight ratio, and
      histologic study. At flushing pressures of 5, 20, and 25 mmHg, uniform and clear
      flushing out of the pulmonary vascular beds was not obtained, resulting in
      postperfusion pulmonary hypofunction and a high incidence of pulmonary edema.
      However, at flushing pressures of 10-15 mmHg, we succeeded in completely flushing
      out the pulmonary vascular beds, and managed to preserve good pulmonary function.
      In conclusion, we determined the optimal flushing pressure for rabbit lung
      preservation to be 10-15 mmHg.

PMID- 8560568
TI  - Resuscitation of ischemically damaged pancreas during short-term preservation at
      20 degrees C by the two-layer (University of Wisconsin
      solution/perfluorochemical) method.
AB  - We have shown that 24-hr preservation by a two-layer (University of Wisconsin
      solution [UW]/perfluorochemical [PFC]) cold storage method allows tissue ATP
      synthesis and makes it possible to resuscitate a canine pancreas subjected to 90
      min of warm ischemia. The purpose of this study was to examine whether increasing
      preservation temperature to 20 degrees C makes it possible to shorten a
      preservation period for recovery of ischemically damaged pancreas grafts. After
      90 min of warm ischemia, canine pancreas grafts were preserved using the two
      layer (UW/PFC) method for 1 to 8 hr at 20 degrees C, and then autotransplanted. A
      K-value of intravenous glucose tolerance test more than 1.0 at 2 weeks after
      transplantation was considered graft survival. ATP tissue levels were measured by
      high performance liquid chromatography at the end of preservation. Pancreatic
      tissue perfusions were measured using an H2 clearance technique after 30 min to 4
      hr of reperfusion. Pancreas grafts subjected to 90 min of warm ischemia were not
      viable (0/5, control group). However, 3- and 5-hr preservations made it possible
      to recover the ischemically damaged pancreas (3/5 and 5/5, respectively),
      although 1- and 8-hr preservations were not successful (0/3 and 0/3,
      respectively). ATP tissue levels in 1-hr-preserved grafts were 2.55 +/- 0.38
      mumol/g dry weight and were significantly lower compared with the levels in 5-
      and 8-hr-preserved grafts, 9.40 +/- 2.09 (P < 0.01) and 7.37 +/- 1.06 (P < 0.01),
      respectively. On the other hand, pancreatic tissue perfusions in 8-hr-preserved
      grafts after 2 hr of reperfusion were 28.50 +/- 7.52 ml/100 g/min and were
      significantly lower than the values in 1- and 5-hr-preserved grafts, 66.0 +/-
      11.22 (P < 0.01) and 57.10 +/- 4.40 (P < 0.01), respectively. It was suggested
      that 1-hr-preservation was not enough to synthesize ATP, which was essential to
      repair damaged cells, although vascular microcirculation at reperfusion was
      maintained and 8-hr preservation incurred microcirculatory disturbances, although
      ATP for repairing damaged cells was synthesized. We conclude that 3- to 5-hr
      preservation at 20 degrees C by the two-layer (UW/PFC) method accelerates ATP
      synthesis, which is essential for repairing damaged cells and protects vascular
      microcirculation. This makes it possible to resuscitate ischemically damaged
      pancreases faster. This method holds promise for pancreas-kidney transplantation
      from cardiac arrest donors.

PMID- 8560569
TI  - Alternate-day steroid dosing improves growth without adversely affecting graft
      survival or long-term graft function. A report of the North American Pediatric
      Renal Transplant Cooperative Study.
AB  - Data from the North American Pediatric Renal Transplant Cooperative Study were
      analyzed to determine the effects of alternate-day (QOD) steroid dosing on
      growth, graft survival, and graft function in children with functioning grafts 12
      months after transplantation. At 12 months after transplantation, 16.8%
      (337/2001) of transplant recipients were receiving QOD dosing. The basis for the
      selection of a steroid dosing regimen cannot be determined from registry data;
      however, the frequency of QOD dosing differed by donor source, race, age at
      transplant, and the occurrence of rejection episodes in the first year. The
      effect of the steroid dosing pattern on growth was evaluated in children
      continuously on either QOD or daily (QD) steroid dosing. The mean change in the
      standardized height scores from 1 month to 24 months after transplantation was
      significantly greater in those on QOD dosing (+0.5 +/- 0.06) than in those on QD
      dosing (+0.1 +/- 0.03). Using multiple regression analyses, better growth was
      associated with QOD dosing, recipient age less than 13 years, lower total steroid
      dose over 48 hr, and lower serum creatinine (all P < 0.001). Graft survival did
      not differ on the basis of the steroid dosing pattern. In a proportional hazards
      model for survival of living donor grafts after 12 months, graft survival was
      negatively associated with the use of QD dosing, black race, rejection episodes
      in the first year, and a higher serum creatinine at 12 months. The survival of
      cadaver grafts was negatively associated with the use of QD steroid dosing,
      recipient age less than 2 years, rejection episodes in the first year, and a
      higher serum creatinine at 12 months. In addition, the decline in graft function
      did not differ between those on QOD steroid therapy and those on QD therapy. We
      conclude that selected pediatric renal transplant recipients receiving QOD dosing
      have better growth than those receiving QD dosing without compromising allograft
      survival or function.

PMID- 8560570
TI  - Double renal transplant from infant donors. A good alternative for adult
      recipients.
AB  - Several groups have reported technical complications and poor graft survival
      rates in kidney transplants from pediatric donors to adult recipients. Increased
      incidences of acute rejections, vascular thrombosis, and early glomerulosclerotic
      lesions have led many groups to abandon this graft combination. Over the last 4
      years, we have set up a program of two-kidney transplantation from cadaveric
      infant donors under age 3 years, which to date includes 15 adult recipients.
      Thirteen of these grafts are currently functioning at least as well as those from
      adult donors, after a mean follow-up of 1.5 years. Our surgical and therapeutic
      procedures have led to a minimization of the early complications reported by
      other groups. With this transplantation procedure, the patients receive double
      the number of nephrons, which will probably give them better long-term function.
      The encouraging results achieved by our group may help change the current
      consideration of pediatric donors as "suboptimal" ones.

PMID- 8560571
TI  - CD40-gp39 interactions play a critical role during allograft rejection.
      Suppression of allograft rejection by blockade of the CD40-gp39 pathway.
AB  - Studies in vivo have documented the importance of CD40-gp39 interactions in the
      development of T-dependent antibody responses to foreign and auto-antigens. In
      this report, we demonstrate that allograft rejection is also associated with
      strong induction of CD40 and gp39 transcripts. When treatment was initiated at
      the time of transplant, MR1, a mAb specific for gp39, induced markedly prolonged
      survival of fully disparate murine cardiac allografts in both naive and
      sensitized hosts. However, when therapy was delayed until postoperative day 5,
      anti-gp39 failed to prolong graft survival. Allografts from recipients treated
      with MR1 from the time of transplantation showed decreased expression of
      transcripts for the macrophage effector molecule, inducible nitric oxide
      synthase, but essentially unaltered expression of B7 molecules and T cell
      cytokine transcripts (interleukin [IL]-2, interferon-gamma, IL-10, and IL-4)
      relative to control allografts. In addition, alloantibody responses in the MR1
      treated mice were profoundly inhibited. However, our studies using B cell
      deficient mice indicated that the ability of MR1 to prolong allograft survival
      was not dependent on B cells. These data suggest that blockade of CD40-gp39
      interactions may inhibit allograft rejection primarily by interfering with T cell
      help for effector functions, rather than by interference with T cell activation.

PMID- 8560572
TI  - Development, stability, and clinical correlations of allogeneic microchimerism
      after solid organ transplantation.
AB  - To assess the development, stability, and clinical relevance of donor-type
      microchimerism, skin and blood were analyzed in heart (n = 53) and liver (n = 18)
      transplant recipients by nested polymerase chain reaction. Microchimerism was
      detectable in 40 (75%) and 13 (72%) patients after heart and liver
      transplantation, respectively. In heart transplantation, chimerism-positive
      patients showed a lower frequency of acute rejection as compared with negative
      patients, although this was only of borderline statistical significance. Repeated
      intraindividual analyses demonstrated variable patterns of microchimerism over
      time, but changes did not correlate to the clinical state. In liver
      transplantation, chimeric state showed no clear correlation with the patients'
      immunological situation. Our results demonstrate that peripheral microchimerism
      frequently develops after different types of organ transplantation and represents
      a dynamic process but without diagnostic value to predict the immunological risk
      for individual patients.

PMID- 8560573
TI  - Coronary artery intimal thickening in the transplanted heart. An in vivo
      intracoronary untrasound study of immunologic and metabolic risk factors.
AB  - This study examined the hypothesis that immunologic factors are the major
      correlates of coronary artery intimal thickening and luminal stenosis. The study
      population included 116 adult heart transplant recipients with a mean age of 44.7
      +/- 12.0 years (89 men and 27 women) undergoing annual coronary angiography and
      intracoronary ultrasound 3.4 +/- 2.7 (range, 1.0-14.6) years after
      transplantation. Mean intimal thickness was obtained from several distinct sites
      along the left anterior descending and/or left circumflex coronary artery by
      intracoronary ultrasound. Coronary artery stenosis defined by angiography was
      classified as mild (< 30% luminal stenosis), moderate (> or = 30-70% luminal
      stenosis), or severe (> 70% luminal stenosis or diffuse pruning of distal
      vessels). Prevalence of any transplant coronary artery disease (TxCAD) was 85% by
      intracoronary ultrasound and 15% by angiography. By multiple regression analysis,
      only average fasting plasma triglyceride level (P < 0.006) and average weight (P
      < 0.007) were significantly correlated with severity of intimal thickening (R =
      0.54, P < 0.0001). Donor age (P < 0.006) and average fasting plasma triglyceride
      level (P < 0.009) were significantly correlated with stenosis by angiography.
      Correlation of multiple immunologic and metabolic factors with intimal thickness
      by univariate analysis suggests a multifactorial etiology for TxCAD. Among the
      multiple univariate correlates of TxCAD, higher fasting plasma triglyceride
      levels and body weight are the only independent correlates of TxCAD. The absence
      of acute rejection as an independent predictor of intimal thickening suggests
      that mechanisms beyond those mediating typical cellular rejection should be
      targeted for advancing our understanding of Tx-CAD.

PMID- 8560574
TI  - Bone marrow transplantation for severe aplastic anemia from genotypically HLA
      nonidentical relatives. An update of the Seattle experience.
AB  - This report updates the results of marrow transplantation at the Fred Hutchinson
      Cancer Research Center for patients with severe aplastic anemia whose donors were
      HLA-nonidentical relatives. Between 1970 and 1993, 40 patients received
      transplants for severe aplastic anemia from related donors other than HLA
      genotypically matched siblings. Nine patients (group 1) were conditioned with
      cyclophosphamide (Cy) at 50 mg/kg for 4 doses and received marrow from
      phenotypically HLA-matched relatives. With the exception of one accidental death,
      all patients are alive and disease free 3-18 years after transplantation. Thirty
      one patients received marrow from HLA-mismatched relatives who differed by one or
      more loci. Fifteen of these patients (group 2) received Cy at 50 mg/kg for 4
      doses without total body irradiation (TBI) and none survived. Because of failure
      to sustain engraftment in 9 of 14 evaluable patients in group 2, the regimen for
      HLA-mismatched patients was changed in 1984 to include Cy at 60 mg/kg for 2 doses
      and TBI was added at 1200 cGy to increase immunosuppression (group 3). Sixteen
      patients in group 3 received marrow grafts after failure to respond to
      immunosuppressive therapy. Eight of the 16 patients in group 3 remain alive
      without disease between 1.5 and 11.3 years after transplantation. In conclusion,
      transplants from phenotypically HLA-identical related donors can be carried after
      Cy alone and results are comparable to those observed with genotypically HLA
      identical siblings. Transplants from related donors mismatched for one or more
      HLA loci require a more intensive conditioning regimen, for example, one
      containing TBI, to achieve sustained engraftment.

PMID- 8560575
TI  - Late hepatic artery thrombosis in liver allograft recipients is associated with
      intrahepatic biliary necrosis.
AB  - Hepatic artery thrombosis (HAT) after liver transplantation is a potentially life
      threatening complication that occurs in 2-25% of patients, depending on several
      risk factors and the patient population studied. Arterial thrombosis occurring
      early after liver transplantation is associated with acute fulminant hepatic
      failure, biliary tract necrosis and leaks, or relapsing bacteremia and is
      associated with a high rate of graft loss and patient mortality. The onset of
      late posttransplant HAT (after 6 months) has been thought to have a more benign
      and often asymptomatic course. The reasons for the differences between the
      manifestations of early and late HAT are not well understood. We reviewed the
      adult liver transplant experience at the University of Cincinnati and found four
      patients with late HAT, three of whom developed severe intrahepatic biliary
      necrosis. Two patients were successfully retransplanted and 1 patient who refused
      retransplantation died. One patient had mild, transient graft damage due to
      gradual arterial stenosis and the development of arterial collaterals prior to
      thrombosis. Late HAT has a significant potential for irreversible graft damage
      requiring retransplantation. Screening for the development of hepatic artery
      stenosis prior to late thrombosis may be worthwhile.

PMID- 8560576
TI  - Tissue pH in cold-stored human donor livers preserved in University of Wisconsin
      solution. A noninavasive clinical study with 31P-magnetic resonance spectroscopy.
AB  - It is not known whether the tissue acidosis that accompanies cold storage is the
      beginning of irreversible cell injury, ultimately leading to cell death, or
      whether it is a natural "protective" mechanism for cells to survive hypoxic
      periods. To answer this question, the tissue pH of 45 cold-stored human donor
      livers preserved in University of Wisconsin solution (UW) was assessed shortly
      before implantation using noninvasive 31P magnetic resonance spectroscopy. We
      conclude that tissue pH during cold storage may be partly dependent upon hepatic
      glycogen stores and donor age. The wide range of tissue pH values that was
      observed at the time of implantation does not result in significant effects on
      cellular damage after transplantation. This indicates that tissue pH is not a
      major determinant for the viability of UW solution-preserved human donor livers,
      as indicated by postoperative hepatocellular damage and liver synthesis function.
      The membrane stabilizing and buffering capacity of UW solution appears to protect
      liver viability against tissue acidosis. Our results also indicate that liver
      tissue pH can be lower than has been previously assumed in the literature without
      significant adverse effects on liver viability.

PMID- 8560577
TI  - Hodgkin's disease after transplantation.
AB  - Hodgkin's disease (HD) has seldom been reported after transplantation. Epstein
      Barr virus (EBV) is present in about 50% of Reed-Sternberg cells in HD developing
      in immunocompetent individuals, but is more frequently found in HD of acquired
      immune deficiency syndrome patients. We report 7 cases of HD that occurred in
      transplant recipients. Clinical and pathological data and studies of EBV reveal
      specific features of HD after transplantation. Six patients received kidney
      transplants and 1 patient received combined kidney and pancreas transplantation.
      Immunosuppressive therapy consisted of cyclosporine, steroids, azathioprine, and
      antilymphocyte globulins. One patient received, in addition, anti-CD3 mAb therapy
      and an EBV+ B cell lymphoma developed. Retrospective EBV serological data from
      patients were collected. Tumors were classified according to pathology. EBV
      studies were conducted by immunohistochemical methods with monoclonal antibodies
      to EBV-latent membrane protein (LMP) or EBV-nuclear antigen 2 (EBNA2), and by in
      situ hybridization for latent nuclear EBV-early RNAs (EBERs). The mean lapse of
      time between transplantation and HD was 49 months. Six patients presented with
      enlarged lymph nodes and 1 patient presented with liver involvement. HD was
      classified as IA in 2 patients, IIA in 3 patients, IIIB in 1 patient, and IVB in
      1 patient. Four patients had primary EBV infection after graft, before HD, and
      the others reactivated latent EBV infection. Histological subtypes were mixed
      cellularity in 6 cases and lymphocytic depletion in 1 case. Latent EBV infection
      was detected with EBERs in all tumors. Reed-Sternberg cells expressed LMP, and
      were negative for EBNA2 expression. Six patients were treated: 2 patients at
      stage I received radiotherapy, and relapsed within 1 year with a more advanced
      stage of HD; chemotherapy was indicated as primary therapy in 5 patients, and as
      salvage therapy in 2 patients; it was associated with radiotherapy in 4 patients.
      Immunosuppressive therapy was reduced in all patients. Four patients were alive
      and in complete remission 18, 25, 31, and 67 months after chemotherapy, with a
      functioning graft in 3 patients. Two patients died of infection. Mixed
      cellularity is the most frequent histological subtype observed in HD occurring in
      transplant patients. EBV is present in all Reed-Sternberg cells. Posttransplant
      HD shows similarities with human immunodeficiency virus-associated HD. These
      facts argue for a role of EBV infection and immunosuppression in the progression
      of HD after transplantation.

PMID- 8560578
TI  - The role of endogenous glucocorticoids on host T cell populations in the
      peripheral lymphoid organs of mice with graft-versus-host disease.
AB  - Previously, we demonstrated that immature CD4+8+ and mature CD4+ thymocyte
      populations were selectively eliminated during murine graft-versus-host disease
      (GVHD) as a consequence of elevated levels of endogenous glucocorticoids. In this
      report, we investigated whether the marked reduction of CD4+8+ and CD4+ thymocyte
      populations would affect host CD4+ and CD8+ T cell populations in the spleens and
      lymph nodes (LN) of mice undergoing GVHD. GVHD was induced in (C57BL/6 x A)F1
      (B6AF1) mice by injecting A strain parental lymphoid cells. Using an antibody
      against H2Kb antigens, labeled host B6AF1 cells were distinguished from unlabeled
      donor A cells. Our results demonstrated a marked deficiency of host CD4+ and CD8+
      T cells in the spleens and LN of GVHD mice on day 21 after GVHD induction. The
      severe reduction of host T cell populations in the peripheral lymphoid organs did
      not appear to result from the elimination of CD4+8+ and CD4+ thymocyte
      populations. However, adrenalectomy before GVHD induction reversed the severe
      loss of both host CD4+ and CD8+ T cell populations in the LN of GVHD mice on day
      21, whereas cortisone treatment of adrenalectomized (ADX) GVHD mice resulted in
      reduction of host LN CD4+ and CD8+ T cell populations similar to that observed in
      non-ADX GVHD animals on day 21. In addition, adrenalectomy markedly improved the
      proliferative response of LN T cells to mitogens when compared with
      immunosuppressed T cells from the LN of non-ADX GVHD mice. In contrast,
      adrenalectomy did not reverse splenic T cell immunosuppression and the marked
      reduction of splenic host T cell populations during GVHD. These results suggest
      that high levels of endogenous glucocorticoids during GVHD play a central role in
      mediating severe deficiency of host T cell populations and inducing severe T cell
      immunosuppression in the LN, but not in the spleen, of GVHD mice.

PMID- 8560579
TI  - In vivo anti-CD3-driven cell activation. Cellular source of induced tumor
      necrosis factor, interleukin-1 beta, and interleukin-6.

PMID- 8560580
TI  - Pharmacodynamic assessment of mycophenolic acid-induced immunosuppression by
      measurement of inosine monophosphate dehydrogenase activity in a canine model.
AB  - The combination of pharmacokinetic and pharmacodynamic (measurement of the
      biological effect) monitoring of immunosuppressive drugs provides a method for
      the optimization of drug dosing. We chose to investigate this using mycophenolic
      acid (MPA), an immunosuppressive drug that mediates its effect by the inhibition
      of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo
      biosynthesis of purines. Using an assay developed for measurement of IMPDH
      activity in whole blood, the concentration required for 50% inhibition of IMPDH
      activity was approximately 200 mg/L (58 +/- 8.3% for whole blood [n = 6] and 55
      +/- 10.0% for isolated lymphocytes). To ascertain the relationship between MPA
      concentration and IMPDH inhibition in vivo, dogs were administered a single dose
      of mycophenolate mofetil, the pro-drug of MPA, at 20 or 40 mg/kg orally.
      Pharmacokinetic analysis revealed that the Cmax of the 40-mg/kg group was
      statistically greater than that of the 20-mg/kg group (P < 0.05). There were no
      statistical differences in the other parameters investigated (area under the
      curve, beta half-life, mean residence time, volume of distribution at steady
      state, and clearance) between the two treatment groups. The half-life was
      calculated at approximately 8 hr for both dose groups. There was also substantial
      variability among the dogs in the absorption and clearance of MPA. An inverse
      relationship was found between the MPA concentration and IMPDH. Maximal
      inhibition of IMPDH activity of 30-40% occurs approximately 2-4 hr after dosing,
      followed by a gradual restoration in enzyme activity. After 24 hr, there is an
      increase in IMPDH activity that exceeds the pre-dosing levels in some cases by 3
      fold. Evaluation of the pharmacokinetic and the pharmacodynamic responses to MPA
      in the canine model suggests that the drug should be administered ever 8 hr to
      optimize its immunosuppressive efficacy. This combined approach can be used for
      optimization of doses of this and other immunosuppressive drugs.

PMID- 8560581
TI  - Successful transfer of immune unresponsiveness to concordant rat islet
      xenografts.
AB  - Indefinite survival of concordant xenogeneic Wistar Furth (WF) rat islet survival
      was obtained by intrahepatic transplants of cultured WF islets and a single
      injection of antilymphocyte sera in C57BL/6 mice. Adoptive transfer of
      splenocytes from mice with established WF islet xenografts produced a marked
      prolongation of survival of WF islets transplanted under the kidney capsule of
      diabetic irradiated (600 rads), naive C57BL/6 recipients (mean survival time =
      48.9 +/- 17.1 days), and three of the recipients were still normoglycemic at 100
      days after transplantation. Adoptive transfer of an equal mixture (3 x 10(7)
      cells each) of these splenocytes with normal splenocytes also prolonged survival
      of the kidney capsule islet xenografts (mean survival time = 26.5 +/- 7.8 days
      vs. 15.2 +/- 5.3 days for controls). In vitro studies on lymphocyte proliferation
      demonstrated a low rate of proliferation of splenocytes from established islet
      xenografts in the presence of irradiated WF splenocytes (stimulation index = 1.6
      vs. 16.2 for naive C57Bl/6 mice), and mixing the cells with control splenocytes
      also decreased the proliferation of splenocytes as compared with controls
      (stimulation index = 5.4 vs. 16.2 in controls). The inhibitory effect was not
      species specific, since splenocytes from mice with established islet xenografts
      also produced a 42% inhibition of proliferation in the presence of irradiated
      Lewis splenocytes. These findings demonstrate that concordant, islet xenograft,
      immune unresponsiveness can be adoptively transferred by splencotyes from mice
      with established islet xenografts.

PMID- 8560582
TI  - Gas-generating systems in acute renal allograft rejection in the rat. Co
      induction of heme oxygenase and nitric oxide synthase.
AB  - Gases are now viewed as biologic messengers, and in this regard, carbon monoxide
      and nitric oxide are incriminated in signaling processes in neural tissue. Carbon
      monoxide is generated by heme oxygenase (HO), an enzyme inducible by heme,
      cytokines, and oxidative stress and considered an antioxidant response; nitric
      oxide is generated by nitric oxide synthase, an enzyme also inducible by
      cytokines. Since mononuclear cells infiltrate the acutely rejecting kidney, and
      foster within the kidney oxidative stress and a cytokine-enriched milieu, we
      examined the expression of these enzymes in acute renal allograft rejection (AR)
      (Brown Norway kidney to a Lewis rat; n = 17) and in control isografts (Lewis
      kidney to a Lewis rat; n = 17). No immunosuppressives were used. We found marked
      induction of HO mRNA and protein in renal allografts at day 5 after
      transplantation. Prominent expression of HO protein, as detected by
      immunofluorescence, was observed in the mononuclear cells infiltrating the renal
      allograft. More than 80% of these cells were macrophages, as identified by
      positive staining with ED1 antibody. ED1+ cells were rare in isografts and did
      not stain for HO. We also found co-expression of mRNA and protein for the
      inducible isoform of nitric oxide synthase (iNOS) in AR at day 5 after
      transplantation. Induction of HO and iNOS may reflect the cellular effect of
      diverse cytokines elaborated in the rejecting kidney. HO may enable the
      macrophage to degrade heme-containing proteins released from erythrocytes and
      other damaged cells; alternatively, induction of HO may defend the macrophage
      against oxidant injury. Increased nitric oxide, as a result of iNOS activity, may
      antagonize the vasoconstrictive effects of a number of mediators (i.e.,
      thromboxane and endothelin) present in acute rejection; conversely, nitric oxide
      may prove cytotoxic through a number of recognized effects. Our studies provide
      the first demonstration of the induction of HO in the rejecting renal allograft
      as well as the first demonstration in vivo for the induction of HO in macrophages
      at the site of an inflammatory response. Such expression, linked as it is to the
      expression of iNOS, indicates that the macrophage mimics the behavior of neural
      cells by generating these gaseous messengers; thus, neural cells are not alone in
      deploying these mediators. Through a number of effects, these products of HO and
      iNOS may influence the nature and severity of tissue injury in AR.

PMID- 8560583
TI  - The F(ab')2 fragment of an anti-ICAM-1 monoclonal antibody attenuates liver
      injury after orthotopic liver transplantation.
AB  - Long-term storage of liver grafts results in increased adhesion of leukocytes
      onto the sinusoidal walls. This eventually leads to posttransplant graft damage
      through disturbances of hepatic microcirculation. Intracellular adhesion molecule
      1 (ICAM-1) is known to be involved in attachment of leukocytes. This study was
      designed to examine whether ICAM-1 participated in the pathogenesis of
      posttransplant liver injury. Inbred Lewis rats were used as both donors and
      recipients to avoid immunoreactivity. Donor livers were stored for either 1 or 6
      hr in ice-cold Euro-Collins solution and subsequently implanted. Expression of
      ICAM-1 was examined immunohistochemically. In some rats that received livers
      stored for 6 hr, the intact IgG (1.0 mg/kg) or the F(ab')2 fragment (0.5 mg/kg)
      of an anti-ICAM-1 mAb (1A29) was administered via the tail vein immediately after
      reperfusion of portal blood. In the group receiving livers stored for 6 hr, ICAM
      1 began to be expressed on the sinusoidal endothelial cells as early as 15 min
      after reperfusion of the portal blood. Strong ICAM-1 expression was observed from
      2 hr up to 24 hr after reperfusion. In contrast, expression of ICAM-1 was not
      evident at any time point after surgery in the 1-hr storage group as well as in
      untransplanted, normal livers. Serum alanine aminotransferase (ALT) levels were
      significantly higher in the 6-hr storage group compared with those of the 1-hr
      storage group (1-hr: 171 +/- 9 IU/L; 6-hr: 825 +/- 109 IU/L, P < 0.05; mean +/-
      SEM) 24 hr after transplantation. Serum ALT levels were markedly reduced by
      treatment with the F(ab')2 fragment of 1A29 (247 +/- 34 IU/L, P < 0.05 vs. 6-hr
      storage group). This was associated with reduced accumulation of leukocytes in
      the liver. In marked contrast, treatment with the intact IgG of 1A29 increased
      serum ALT levels dramatically (5297 +/- 634 IU/L, P < 0.05 vs. 6-hr storage
      group) and reduced serum complement. Histological examination revealed focal
      hepatocellular necrosis 24 hr after surgery in the 6-hr storage group. Treatment
      with the F(ab')2 fragment decreased the liver damage; in marked contrast,
      treatment with the intact IgG strikingly aggravated the injury, as characterized
      by massive necrosis throughout the liver. Liver damage caused by the intact IgG
      might be related to activation of the complement system by the Fc portion of the
      antibody. Taken together, these results indicate that ICAM-1 is involved in the
      mechanism of postoperative liver injury following liver transplantation.

PMID- 8560584
TI  - Is the lesser growth of African schoolchildren essentially prejudicial to their
      present and future health?
AB  - In African and other Third World countries, 20-50% of schoolchildren lie under
      the 5th centile of US National Center for Health Statistics (NCHS) growth
      reference standards for weight- and height-for-age. Such lesser growth,
      orthodoxly, categorizes those affected as malnourished, at greater risk of
      disease, of lesser intelligence, and in need of nutritional supplementation.
      Questions arising include: 'Are there limitations to the application of NCHS
      reference standards?' In African schoolchildren, is lesser growth attributable
      largely, or marginally, to insufficient food intake? How powerful are the non
      dietary influencing factors? What are the associated disadvantages to health?
      Conversely, could lesser growth around puberty even be beneficial respecting
      possible lessening of subsequent risk of degenerative diseases? Discussion
      indicates that there are numerous complexities in the whole subject of
      anthropometry, malnutrition and its stigmata, and interventions, dietary and non
      dietary, in the youth of poor populations. In view of the invariably low health
      funds available in Third World countries, only intervention measures of proven
      significance to pupils' health warrant implementation.

PMID- 8560585
TI  - Recent observations on the epidemiology of kala-azar in the eastern and central
      states of the Sudan.
AB  - The main endemic area of kala-azar (visceral leishmaniasis) in the Sudan is in
      Eastern State and the Blue Nile area of Central State. In order to obtain more
      recent information about kala-azar in both States, the major hospitals and health
      centres were visited, the physicians and medical assistants interviewed and
      available records inspected. In Eastern State a cross-sectional survey of one
      village was carried out and a longitudinal population-based study of another
      village started. In this State, after a decline since 1985, a sharp increase in
      the number of cases was noted from 1991 onwards. This increase was seen in large
      areas, especially along the Rahad and Dinder Rivers. In contrast, in Central
      State, there was a decline in the frequency of the disease since the 1960s in the
      area around Sennar and Singa, which was regarded as a hyperendemic focus up to
      about 30 years ago. It was hypothesized that this decline may be related to the
      extensive agricultural development with regular insecticiding and the
      deforestation of the area. Several aspects with regard to transmission of kala
      azar are discussed.

PMID- 8560586
TI  - Quantitative interpretation of coprocultures in a population infected with
      Oesophagostomum bifurcum.
AB  - Coproculture is used in northern Togo and Ghana in the research on
      Oesophagostomum bifurcum, a common parasite of man in these regions. Prior to a
      follow-up study to investigate patterns of reinfection in Oesophagostomum and
      hookworm, it was attempted to evaluate the relevance of counting larvae for the
      assessment of the intensity of infection at the population level. Of 102 samples,
      one egg count (Kato-smear) and three coprocultures were carried out. Frequency
      distributions of counts of larvae of Oesophagostomum and of hookworm isolated in
      three coprocultures, showed log-normality. There was a highly significant
      correlation between egg counts and the combined number of Oesophagostomum and
      hookworm larvae (Spearman rank correlation test, r = 0.74, p < 0.01). It is
      concluded that the mean larval counts of three coprocultures can be interpreted
      quantitatively, as normally done for egg counts. A quantitative classification of
      larval counts is proposed.

PMID- 8560587
TI  - Reinfection patterns of Oesophagostomum bifurcum after anthelmintic treatment.
AB  - Subjects infected with the adult worms of Oesophagostomum bifurcum, diagnosed
      through semiquantitative detection of characteristic third stage larvae, were
      treated in the middle of the dry or in the middle of the rainy season with two
      different dosages of albendazole. A third group was not treated. The pattern of
      reinfection after treatment was analysed. Transmission of Oesophagostomum
      infection appeared to be limited to the rainy season and the rate of reinfection
      was independent of the dose of albendazole received. The impact on transmission
      of developing stages that might survive in the nodules in the intestinal wall is
      discussed.

PMID- 8560588
TI  - Culture of Salmonella typhi and Salmonella paratyphi from blood and bone marrow
      in suspected typhoid fever.
AB  - We studied the yield of blood and bone marrow (BM) cultures in 145 patients
      clinically suspected of typhoid fever (TF) in Indonesia. The objectives were to
      compare the positivity of blood culture using 3 ml versus 10 ml of blood and to
      examine in how far specific antibiotic treatment for TF interfered with the
      positivity of BM culture. Blood for culture was collected before antibiotic
      treatment was initiated in hospital and BM 1 to 10 days after the start of
      treatment. Cultures were performed with Oxgall subcultured on SS agar. Seventy
      nine per cent of patients was treated for 14 days or more with oral
      chloramphenicol, 18% with chloramphenicol followed by ampicillin or cotrimoxazol
      and 3% with other antibiotics. Cultures were positive for Salmonella typhi or S
      paratyphi A in 57 of the 145 patients (39.3%) when 3 ml of blood was cultured and
      in 58 (40%) when 10 ml of blood was cultured. BM culture was positive despite
      antibiotic treatment in 70 patients (48.2%); this positivity was significantly
      greater than that of blood cultures (p < 0.05). When we considered the positivity
      of BM culture in relation to the number of days on antibiotics in hospital, the
      yield of BM culture remained apparently unchanged during the first 5 days of
      treatment. This may be the consequence of slow elimination of S.typhi or
      S.paratyphi by the antibiotics used and could be responsible for relapses.

PMID- 8560589
TI  - Cutaneous manifestations of liver cirrhosis in an African (negroid) population.
AB  - Sixty negroid patients with liver cirrhosis were examined for their cutaneous
      features at the University College Hospital, Ibadan, Nigeria. When compared with
      age and sex matched controls, the cirrhotic patients had significantly lower body
      temperature, onycholysis and hyperpigmented palmo-plantar macular areas (p <
      0.05). Until now, these features have not been previously associated with liver
      cirrhosis. Other cutaneous signs such as sparse silky hair, female public hair
      pattern, digital clubbing, leuconychia, ankle oedema and corneal jaundice are
      found more commonly in cirrhotic patients (p < 0.05) and have been previously
      documented. All these features in a middle-aged man with hepatomegaly may be of
      added distinctive value particularly in many rural centres in tropical countries
      where facilities for definitive histological diagnosis are frequently lacking.
      The relevance of some of these cutaneous features in the light of the pattern
      described in Caucasians is also discussed.

PMID- 8560590
TI  - The changing pattern of mortality in an African medical ward.
AB  - The pattern of adult medical deaths in Queen Elizabeth Central Hospital,
      Blantyre, Malawi was documented over a 12 month period between April 1992 and
      March 1993. Results were compared with mortality data collected from the same
      wards in the pre-AIDS era in 1973. Tuberculosis and AIDS together accounted for
      49% of all medical deaths in 1992-93. Eighty-two per cent of deaths occurred in
      the age group 13-49 years; tuberculosis, AIDS, gastroenteritis, pneumonia,
      pyogenic meningitis and septicaemia were the most important causes of death in
      these young patients. These findings are very different to those observed in the
      same wards 20 years previously when tuberculosis was responsible for 13% of
      deaths and there were no deaths due to AIDS. The predicted upsurge in AIDS
      related deaths in sub-Saharan Africa in the 1990s will have grave consequences
      not only for the health sector, but for the social and economic fabric of the
      countries concerned.

PMID- 8560591
TI  - Effect of socio-cultural beliefs on patients' perception of leprosy. The gender
      factor.
AB  - A study to determine the gender factor in the effect of socio-cultural beliefs on
      patients' perceptions of leprosy was conducted with the participation of 293
      leprosy patients in Kaduna State, Nigeria. Results indicate that, contrary to
      popular belief, the male model is not the single interpretative model for leprosy
      as far as socio-cultural aspects are concerned. These differences are analysed
      and appropriate suggestions made.

PMID- 8560592
TI  - Acute psychosis after mefloquine. Report of six cases.
AB  - A self-limiting psychosis characterized by acute onset of visual and auditory
      hallucinations and poor sleep developed in six adults between 8 and 24 hours
      after oral administration of 750-1500 mg of the antimalarial mefloquine. All
      patients had no personal or family history of psychosis and were neurologically
      and mentally normal before mefloquine ingestion. These cases illustrate that
      acute psychotic symptoms may occur in patients treated with mefloquine.

PMID- 8560593
TI  - Colonic perforation caused by taeniasis.
AB  - In this report, a case of colonic perforation caused by Taenia saginata is
      presented. Preoperative ultrasonographic examination showed a 'pseudokidney sign'
      suggestive of colonic carcinoma. Clinical and ultrasonographic appearance of this
      rare case and the possible perforation mechanism are discussed.

PMID- 8560594
TI  - Fluoroquinolone antimicrobials.

PMID- 8560595
TI  - Multiple high doses of vitamin A.

PMID- 8560596
TI  - Effects of secondary hyperparathyroidism on cardiac function in pediatric
      patients on hemodialysis.
AB  - Cardiovascular complications are an important cause of morbidity and mortality in
      chronic hemodialysis patients. In order to examine the effect of parathyroid
      hormone (PTH) and vitamin D on left ventricular functions, 11 patients between
      the ages of 13 and 18 years on regular hemodialysis were investigated using M
      mode echocardiography and systolic time intervals. The ratio of the pre-ejection
      period to the left ventricular ejection time was found to be 0.38 +/- 0.02 (range
      (0.25 +/- )>50) and was elevated above normal in five of the 11 patients
      examined. Four of these patients has hypertension and one had severe anemia. The
      left ventricular ejection fraction was 55 +/- 2.54% and fractional fiber
      shortening was 31.55 +/- 2.26%, both of which were within normal limits for age.
      Although the velocity of circumferential fiber shortening was within normal
      limits in the majority of cases, the mean value was 1.437 +/- 0.11 circ/s, which
      is above normal for this age period. PTH levels were between one and 4.70 ng/ml.
      All of the hemodialysis patients had been receiving 1 alpha hydroxy
      cholecalciferol and had normal calcium levels. Although they had high PTH levels,
      most of these patients displayed normal myocardial contractility. No significant
      correlation was obtained between increment in PTH levels and myocardial function
      indices. These results imply that PTH is not the only factor affecting myocardial
      functions. Since all of these patients have received vitamin D therapy for long
      periods, we suggest that vitamin D may have prevented the deleterious effect of
      PTH on myocardial function.

PMID- 8560597
TI  - The effects of contrast media on renal function in children: comparison of ionic
      and non-ionic agents.
AB  - Nephrotoxicity is a common side effect of intravascular contrast media (CM).
      Although nephrotoxicity of ionic CM has been widely demonstrated, recent studies
      suggest that newer and more costly non-ionic agents are not less nephrotoxic. We
      studied the hemodynamic, hematologic and nephrotoxic effects of CM prospectively
      in 38 patients (ages six months-16 years) with or without risk factors
      predisposing to nephropathy and compared ionic and non-ionic CM. We performed
      intravenous urography (IU) with a ionic CM, sodium meglumine diatrizoate (n = 18)
      and a non-ionic CM, iohexol (n = 20). The patients were divided into three groups
      according to glomerular filtration rate (GFR) [GFR < or = 50 (n = 9), 50-80 (n =
      13), > or = 80 ml/min/1.732 (n = 26)]. Eleven patients had risk factors for
      nephropathy. Blood pressure, heart rate, ECG, urine and blood samples were
      obtained 24 hours and one hour before as well as one, 24, and 48 hours after CM
      infusion. Although a significant increase was found in urine specific gravity,
      protein/creatinine ratios and serum Na and creatinine levels, the increased
      levels were within normal limits. We observed a significant reduction in Hb and
      Htc and urinary prostaglandin E1 levels. Many of the changes observed in the
      urine and serum values after the use of CM were minor, insignificant and
      transient, later returning to their initial values. The GFR levels, the presence
      of risk factors and the use of ionic vs. non-ionic CM had no effect on the
      results. The elevated urinary basal beta-2-microglobulin levels further increased
      after CM in patients with low GFRs. It was concluded that non-ionic CM was not
      superior to ionic CM in patients with GFRs greater than 50 ml/min regardless of
      predisposing risk factors. One of the non-invasive radiological methods is
      advised instead of IU in patients with low GFRs.

PMID- 8560598
TI  - Comparative efficacy of rice-ORS and glucose-ORS in moderately dehydrated Turkish
      children with diarrhea.
AB  - The efficacy of precooked rice-based (50 g/L) oral rehydration solution (R-ORS)
      was compared with standard glucose-based ORS (G-ORS) in a randomized controlled
      trial in 79 children who were moderately dehydrated due to diarrhea. ORS intake
      rate and weight gain after rehydration were found to be similar in the two
      treatment groups (p > 0.05). The time necessary for rehydration was significantly
      lower in the R-ORS-treated group than in the G-ORS-treated group (5.2 +/- 2.2 and
      7.5 +/- 3.4 hours, respectively, p < 0.05). Although the mean serum bicarbonate
      levels were significantly increased in both treatment groups at the end of the
      treatment, a significant increase in the mean pH value was observed in only the R
      ORS treated group (p < 0.05).

PMID- 8560599
TI  - Serum osteocalcin levels in type I diabetes mellitus.
AB  - Serum osteocalcin levels are a marker of bone formation. In this study, bone and
      mineral metabolism in type I diabetes mellitus (DM) were investigated, and the
      changes related to diabetic microvascular complications were examined. Serum
      calcium (Ca), inorganic phosphate (P), osteocalcin (OC) and parathyroid hormone
      (PTH) levels were measured in 42 type I diabetic subjects. Diabetics were
      subdivided into those with or without complications. Age and sex-matched control
      subjects were used for comparisons with the diabetic groups. Serum P and PTH
      levels were not different from those of controls. Serum Ca levels were
      significantly increased (p < 0.001) although the values were within the normal
      range. OC levels were significantly lower in the complicated (retinopathy and/or
      protenuria) diabetic group (p < 0.005). In Type I diabetes mellitus, the serum OC
      level is influenced by the presence of microvascular complications.

PMID- 8560600
TI  - Age-specific seroprevalence of hepatitis B virus infection.
AB  - In this study, we have tried to determine the age-specific seroprevalence of
      hepatitis B virus (HBV) infection and to make some conclusions about the mode of
      transmission and vaccination strategy which should be chosen in Turkey. Eight
      hundred and one patients between the ages of six months and 60 years of age were
      included in this study. According to the HBV serologic markers, (HBsAg, Anti-HBc
      and Anti-HBs), HBsAg positivity and HBV exposure rates were 6.5% and 32.8%,
      respectively. HBsAg positivity was 6.6% under one year of age. The highest rate
      of HBsAg positivity was in the 6-10 year age-group (p < 0.05). The prevalence of
      total hepatitis B virus seropositivity increased with age (p < 0.05). The HBV
      exposure rate was higher in males than in females (p < 0.05). It was concluded
      that HBV infection is an important infection in Turkey and is acquired very early
      in life. A mass hepatitis B vaccination strategy should be thus chosen in Turkey.

PMID- 8560601
TI  - Salmonella typhi infections. A 10-year retrospective study.
AB  - Enteric fever is still a common health problem in many countries, especially in
      children. Thus a ten-year retrospective study was carried out to evaluate the
      clinical and laboratory properties of enteric fever and the incidence of
      antimicrobial resistance in children. Throughout the past 10 years, Salmonella
      was isolated in 105 patients by blood culturing, 27 of which were Salmonella
      typhi. Most of the patients were above the age of two. Besides the typical
      symptoms and signs of enteric fever, 29.2% of the patients had some neurologic
      findings. Besides, 68.5% had elevated liver enzymes while only 44.4% had
      hepatomegaly with or without splenomegaly. Anemia was present in 44%, leukopenia
      in 16% and leukocytosis in 11.1% of the cases. The emergence of antimicrobial
      resistance during the last five years against ampicillin, chloramphenicol and
      trimetoprim-sulfamethoxazole has created a challenge in treating these
      infections.

PMID- 8560602
TI  - The effect of high-dose methylprednisolone on CD34-positive bone marrow cells in
      the children with acute myeloblastic leukemia.
AB  - The expression of CD34 antigen on the surface of bone marrow (BM) cells during
      remission induction was studied in 20 patients with CD34-negative acute
      myeloblastic leukemia (AML). The patients were given high-dose methylprednisolone
      (HDMP) alone for one week, after which time mitoxantrone and low-dose Ara-C were
      added. BM cells from all patients were studied one, two and four weeks after
      initiation of treatment to evaluate CD34 antigen expression using a three-step
      peroxidase antiperoxidase staining technique. The mean percentage of CD34
      positive BM cells was 5.3% at presentation, increasing to 15.6% in the first
      week, 12.9% in the second week and 21.7% in the fourth week of therapy. During
      the same period the mean percentages of the initial BM blasts decreased from 64%
      to 22%, 7% and 2% in the first, second and fourth weeks of therapy, respectively.
      The increase in the CD34-positive BM cells one week after HDMP treatment alone
      suggests that HDMP directly or indirectly stimulates CD34-positive hematopoietic
      progenitor cells while decreasing BM blasts in patients with AML.

PMID- 8560603
TI  - Should an echocardiographic scan be done routinely for infants of diabetic
      mothers?
AB  - Several cardiologic pathologies are seen in infants of diabetic mothers (IDMs).
      Though asymmetrical septal hypertrophy (ASH) is a frequent pathology in IDMs, it
      is not routinely searched for with an echocardiographic scan. We have performed
      an echocardiographic examination for all IDMs (56 neonates) hospitalized between
      January 1987 and December 1992 in our neonatology and neonatal reanimation units.
      Of 56 patients, the diagnosis of 17 cases of ASH 930%) was made. The group with
      ASH (17 neonates) had a greater corporeal index than the group without ASH (39
      neonates) (p < 0.05). Four of the 17 IDMs (24%) with ASH and one of the 39 IDMs
      (3%) without ASH presented with a cardiac insufficiency (p < 0.05). ASH is a
      pathology which should be searched for routinely IDMs.

PMID- 8560604
TI  - Renal amyloidosis in childhood. An overview of the topic with 25 years
      experience.
AB  - Amyloidosis is a heterogeneous group of diseases characterized by extracellular
      accumulation of an eosinophilic, hyalin and proteinaceous material containing
      mucopolysaccharide substance in various tissues and organs. Knowledge about the
      chemical structure of amyloid fibril proteins has led to the recognition of
      various forms of amyloidosis including Amyloid-A (AA), Amyloid-L (AL),
      hereditary, senile, dialysis-related, localized and cerebral amyloidosis. It is
      now recognized that all types of amyloid contain amyloid P (AP) component which
      is derived from the serum amyloid P component, a normal circulating glycoprotein
      and a member of the pentraxin family. A recent classification proposed by WHO
      IUIS (Nomenciature Subcommittee) is based on the chemical nature of amyloid
      fibris rather than their clinical and pathologic features. The kidneys are
      frequently involved, and renal failure is the major cause of death. Childhood
      renal amyloidosis is almost always secondary (reactive, AA type) and usually
      associated with chronic inflammatory, infectious and heredofamilial diseases. In
      developed countries, rheumatoid arthritis is the most common cause of renal
      amyloidosis, while in developing countries patients with familial Mediterranean
      fever (FMF) (untreated) and chronic suppurative infections constitute a large
      proportion of renal amyloidosis cases. No specific therapy is currently available
      for amyloidosis. Once renal amyloidosis develops, progress to end-stage renal
      failure is almost inevitable within 2-13 years. The aim of treatment is to give
      effective supportive therapy and to control the underlying diseases by
      colchicine, alkylating agents and appropriate antibiotics. The prognosis of
      patients with end-stage renal failure can be improved by maintenance dialysis and
      renal transplantation. The growing knowledge about the pathogenesis and chemical
      nature of amyloid fibris may open up further avenues for the discovery of
      specific therapeutic modalities against amyloidosis.

PMID- 8560605
TI  - Primary osteosarcoma presenting in axial bones in childhood.
AB  - Six cases of osteosarcoma occurring between 1971 and 1992 and involving the axial
      bones were reviewed. They constituted 4% of 129 osteosarcomas occurring in the
      skeleton in childhood during the same period at our center. The patients' ages
      ranged from eight to seventeen years. Four of the six patients were female. The
      distribution of axial bones of osteosarcoma was as follows: one case was in the
      vertebrae, two cases in the craniofacial bones (maxilla and mandible), two cases
      in the pelvis and one case in the ribs. The prognosis was very poor, with only
      one case of mandible osteosarcoma still alive. The other five patients died three
      to sixteen months after diagnosis. A combination of wide surgical resection and
      aggressive chemotherapy may offer the best chance for longterm survival.

PMID- 8560606
TI  - A case of adenosine deaminase-negative severe combined immunodeficiency with
      neurological abnormalities.
AB  - Presented here is a 17-month-old adenosine deaminase-deficient, severe combined
      immunodeficient patient with chest symptoms, oral ulcer, neurologic
      manifestations, head lag, spasticity and developmental delay in motor functions.
      Antibiotics, systemic antifungal agents, intravenous immunoglobulins and partial
      exchange transfusions with irradiated fresh red cells were given. No other mode
      of therapy for adenosine deaminase (ADA) deficiency was available at that time.
      Amelioration of neurologic manifestations within one month of therapy with
      irradiated fresh red cell exchange transfusions suggests that these
      manifestations may have resulted from accumulated toxic metabolites. However, no
      improvement was seen in the course of infection and oral ulcer, and the patient
      died of respiratory failure on the 48th day of admission.

PMID- 8560607
TI  - Unusual malformations in occult spinal dysraphism.
AB  - Two cases of occult spinal dysraphism with different clinical symptoms, signs and
      congenital pathologies are presented. One had malformations including scoliosis,
      dermoid tumor, hydromyelia, diastematomyelia, dermal sinus, low conus, vertebrae
      anomalies and dextrocardia. The occurrence of dextrocardia in association with
      occult spinal dysraphism was found to be extremely unusual. The second case is
      presented in relation to the rarity of teratoma with dermal sinus and tethered
      cord in the lumbar area. Myelography, computed tomography, (CT), Myelo CT and
      magnetic resonance were used in making a diagnosis.

PMID- 8560608
TI  - Biliary ascariasis. A case report.
AB  - Ascaris lumbricoides is a worldwide intestinal infestation that may cause various
      complications. Biliary ascariasis, however, is a rare condition. We describe a
      child with biliary ascariasis. The patient's clinical symptoms were pain,
      vomiting and abdominal tenderness, and she was thought to have acute
      appendicitis. However, laboratory examination revealed high serum alkaline
      phosphatase and amylase levels, and ultrasonography and percutaneous
      cholangiography demonstrated biliary ascariasis. The patient was successfully
      treated with mebendazole and antispasmolytic drugs.

PMID- 8560609
TI  - Splenic abscess due to brucella in childhood. A case report.
AB  - An eleven-year-old male was diagnosed with multiple splenic abscesses due to
      brucella. He was treated only with antibiotics. Although splenic abscess is very
      rare in childhood, in febrile patients with upper quadrant abdominal pain,
      tenderness and splenomegaly, splenic abscess should be suspected especially in
      epidemic regions. Diagnosis can be confirmed by ultrasonography and computerized
      tomography.

PMID- 8560610
TI  - Endophthalmitis in a young child with meningococcal meningitis.
AB  - Meningococcic meningitis is still a serious infection with high rates of
      morbidity and mortality. It is associated with severe complications. In recent
      years ocular complications have occurred less frequently, and endophthalmitis has
      been recognized as a rare complication. We present a case of meningococcic
      meningitis complicated by endophthalmitis.

PMID- 8560611
TI  - Cyclosporin-induced remission in an infant with alkylating agents-resistant
      nephrotic syndrome. A case report.
AB  - The efficacy of cyclosporin-A, a potent immunosuppressive agent, has not been
      clearly proven in the management of childhood nephrotic syndrome. The occurrence
      of early relapse as the dose of cyclosporin is tapered or as soon as the drug is
      stopped and the potential nephrotoxic effects of prolonged treatment have caused
      it to be used in limited cases. We report an eighteen-month-old boy with steroid
      toxicity and alkylating agents-resistant nephrotic syndrome, who subsequently
      went very quickly into remission lasting at least one year after receiving
      cyclosporin-A for only three months.

PMID- 8560612
TI  - Infantile myofibromatosis. A case report.
AB  - Infantile myofibromatosis is a rare mesenchymal disorder of infancy characterized
      by the formation of tumors in the skin, muscle, viscera, bone and subcutaneous
      tissue. The etiology of the disorder is unknown. We describe here a newborn with
      multiple infantile myofibromatosis, peritonitis and intestinal perforation.
      Surgery revealed multiple intestinal obstructions and jejunal perforation due to
      intestinal tumors; consequently, a jejunostomy was performed. The patient was
      maintained on total parenteral nutrition and oral semiliquid infant formula for
      two months, however, he died due to multiple attacks of diarrhea and septicemia.

PMID- 8560613
TI  - Neonatal form of hypophosphatasia. A case report.
AB  - Hypophosphatasia is a rare (1/100,000), inherited inborn error of metabolism
      characterized by low serum and tissue alkaline phosphatase activities resulting
      in skeletal abnormalities. Four clinical forms are recognized depending on the
      age of diagnosis. Since treatment is not available and the prognosis is always
      lethal, detection of index cases and prenatal diagnosis is subsequent pregnancies
      is very important. Here we report a case with the most severe form of
      hypophosphatasia associated with lung hypoplasia.

PMID- 8560614
TI  - Bernard-Soulier-like functional platelet defect in myelodysplastic syndrome and
      in acute myeloblastic leukemia associated with trilineage myelodysplasia.
AB  - Platelet function was studied in a child with myelodysplastic syndrome (MDS:
      refractory anemia with an excess of blasts) and a child with acute myeloblastic
      leukemia (AML-M6) associated with trilineage myelodysplasia (TMDS). An acquired
      Bernard-Soulier-like platelet defect was considered in both patients with the
      findings of prolonged bleeding time and abnormally large platelets that failed to
      aggregate in response to ristocetin. In contrast to findings in von Willebrand's
      disease, the abnormal response of platelets to ristocetin could not be corrected
      by the addition of normal flesh plasma. The detection of abnormal platelet
      aggregation response to ristocetin may be a useful diagnostic finding for clonal
      disorders causing impaired platelet function in MDS and coexistent TMDS
      associated with AML. Further studies of ristocetin-induced platelet aggregation
      in a large number of these patients are required.

PMID- 8560615
TI  - A case of childhood shigellosis with mutism.
AB  - Bacillary dysentery, an acute infection caused by various strains of Shigella, is
      characterized by abdominal pain, tenesmus, and diarrhea with mucus, pus and
      blood. Neurologic manifestations including meningismus, delirium and convulsions
      may accompany the infection. We describe a thirteen-year-old girl who presented
      with headache, convulsion and loss of consciousness at the onset and developed
      diarrhea with blood and pus after hospitalization. The diagnosis of shigellosis
      was based on clinical data and isolation of the microorganism in the stool
      specimen. After improved physical functions, the patient developed mutism that
      continued for two days in the course of her illness, despite having no history of
      neurologic or psychological problems. She was diagnosed by a psychiatrist with
      organic mental syndrome NOS (Not Otherwise Specified) according to DSM-III-R
      criteria. None of the conditions that may cause mutism could be confirmed. This
      is the first reported case of mutism accompanying shigellosis.

PMID- 8560616
TI  - Unilateral agenesis of the sternocleidomastoid muscle.
AB  - An eight-year-old girl with an asymmetrical appearance of the neck is presented.
      Physical examination and ultrasonographic (USG) findings revealed the absence of
      the patient's right sternocleidomastoid muscle.

PMID- 8560617
TI  - [Ugeskrift and the readers].

PMID- 8560618
TI  - [Decreasing vaccination rate--increasing risk of epidemics].

PMID- 8560619
TI  - [Molecular biology in acute myeloid leukemia].

PMID- 8560620
TI  - [Ugeskrift's 1995 survey of readers. A questionnaire study of random population
      of readers of Ugeskrift].

PMID- 8560621
TI  - [Diagnosis and treatment of conjuncitivitis].
AB  - Conjunctivitis is a frequent reason for consulting a doctor. Most often treatment
      consist of antibiotics, even though sensitive bacteria are only rarely
      demonstrated. In our part of the world conjunctivitis is self-limiting, and it
      may be worth considering the effect of treatment, if any. With this in mind,
      diagnosis and differential diagnoses are reviewed, and with regard to treatment
      distinctions are made between neonatal conjunctivitis (gonococcus, chlamydia,
      virus), conjunctivitis in children (symptoms of upper respiratory tract
      infections), and conjunctivitis in adults and the elderly (dry eyes, epiphora in
      ectropion).

PMID- 8560622
TI  - [Male breast cancer. A review].
AB  - Male breast cancer is a rare disease, making up less than 1% of all breast
      cancers. A review of the literature does not disclose major differences between
      male and female breast cancer regarding etiological, prognostic or diagnostic
      features. In male breast cancer endocrine therapy is more widely used, but there
      are otherwise no differences in the therapeutic strategies used.

PMID- 8560623
TI  - [Individual-based statistics on drug utilization].
AB  - The Danish retail pharmacies' drug subsidy system is completely computerised. The
      data are person-identifiable, making it possible to chart the population's drug
      use from the perspective of the individual users. We undertook an analysis to
      explore the potential of this data source and to analyse the heavy drug users
      specifically. The analysis encompassed all 890,352 prescriptions presented by
      Odense citizens in 1991. There was a total sales volume of 32 million defined
      daily doses, consumed by 113,468 adult drug users, corresponding to 65.1% percent
      of the adult population. We found 2388 heavy drug users defined by an annual
      purchase of more than 2000 defined daily doses. Heavy drug users accounted for
      1.4% of the adult population and 22.9% of drug sales. Heavy drug users were
      remarkably well characterised by their main therapeutic class which constituted a
      median of 47% of their drug use. A median of 97% of each heavy user's drugs were
      issued by one main prescriber. We conclude that heavy drug use generally can be
      ascribed to severe disease rather than to irresponsible prescribing. For the most
      important drug classes, we present various epidemiological measures of drug use,
      including one-year prevalence, incidence, duration of therapy and some measures
      of skewness in utilization. If analysed regularly these measures can disclose
      subtle trends in clinical drug use that would not be evident from the wholesale
      figures.

PMID- 8560624
TI  - [Occurrence of sexual abuse of children referred to a pediatric department over a
      5-year period].
AB  - The study concerns 287 children, who were referred to and examined by the
      paediatric department's clinical psychologist. Evidence of sexual abuse was
      observed in 29 of the children (23 girls and 6 boys). Sexual abuse was initially
      suspected in 15 children; the suspicion was confirmed in 11 cases and rejected in
      four cases. The remaining 18 patients had been admitted because of somatic
      complaints and sexual abuse was later uncovered in the psychological examination.
      The somatic problems originated in different organ systems: Five from the
      gastrointestinal system, five from the urogenitary system, three from the
      endocrinological system, two from the locomotor system, two enuresis/encopresis
      and one from the central nervous system. Sexual intercourse was completed in
      seven cases, four with vaginal abuse and three with anal abuse. Four children
      were subjected to oral abuse. Sexual abuse through touching was cited in 14
      cases. In all cases the children were abused on more than one occasion. In 65%
      the perpetrator was a family member. The perpetrator in five cases were 15 year
      old boys. Sex, age, nature of abuse, and frequency is described. Sexual abuse
      within the family is described. It is concluded that sexual abuse was found in
      10% of 287 children referred to the psychologist in a paediatric department
      during the period from 1988-1992. Sexual abuse as a diagnosis must be considered
      in situations with uncertain pathological pictures, behavioral changes and
      problems in learning. It is important to know the different types of sexual abuse
      and their expression in children. Maternal abuse was often seen.

PMID- 8560625
TI  - [Profile of pediatric diseases and symptoms in Southern Greenland. Experiences of
      a consultant visiting in 1992].
AB  - During a scheduled visit to southern Greenland in 1992, the pediatric consultant
      registered signs and symptoms that had led to the children being brought for
      examination, and simultaneously registered the actual frequency of asthma,
      epilepsia and cerebral palsy. A total of 211 children or 8% of the background
      population under the age of fifteen were examined. The point prevalence of asthma
      was 1.1% which was considered to be an absolute minimum value due to selection of
      patients. The point of epilepsy was 0.6% and cerebral palsy 0.3%, a surprisingly
      high prevalence compared to prior investigations and actual patient selection.
      The consultant was met as well by a broad spectrum of pediatric problems, many of
      the social pediatric type. In conclusion, the importance of yearly visits is
      maintained along with a need of instruction of the local local health personnel.
      A systematic registration of cerebral palsy cases is required in order to
      implement necessary prophylactic intervention. Contact between the Greenlandic
      and the Danish health services could be intensified by the use of electronic
      media.

PMID- 8560626
TI  - [Extra-nasal microscopic dacryocystorhinostomy].
AB  - A microsurgical extranasal dacryocystorhinostomy, incorporating the lacrimal sac
      into the nasal cavity by creating a flap of the lacrimal sac mucosa and suturing
      it to the nasal mucosa is described. The results from 81 patients (84 eyes) with
      chronic epiphora operated during the period of 11 years from 1980 to 1991 are
      described and analyzed. The long term results on 84 eyes with a median
      observation time of five years demonstrated good stability of the primary
      results. Only one patient (2%) with distal tear duct stenosis had chronic
      epiphora at the re-evaluation.

PMID- 8560627
TI  - [Angioneurotic edema in relation to therapeutic use of angiotensin-converting
      enzyme inhibitor].
AB  - Angioneurotic oedema secondary to angiotensin-converting enzyme (ACE) inhibitors
      is a rare condition, but it is a side effect which is likely to be seen more
      frequently because of the increased use of these drugs in the treatment of heart
      failure and hypertension. We report two cases which illustrate problems in the
      diagnosis and management of this life-threatening condition, and also demonstrate
      that angioedema re-occurs if the ACE inhibitor is not discontinued. If angioedema
      is suspected, therapy with any angiotensin converting-enzyme inhibitor should be
      discontinued promptly, respiratory distress should be treated appropriately, and
      subsequent therapy should be initiated with an agent from an alternative class of
      drugs.

PMID- 8560628
TI  - [Research strategy--research planning].

PMID- 8560629
TI  - [Mutations in thyrotropin receptors as a cause of thyroid dysfunction].

PMID- 8560630
TI  - [Cancer and vitamin C].

PMID- 8560631
TI  - A simulation algorithm for ultrasound liver backscattered signals.
AB  - In this study, we present a simulation algorithm for the backscattered ultrasound
      signal from liver tissue. The algorithm simulates backscattered signals from
      normal liver and three different liver abnormalities. The performance of the
      algorithm has been tested by statistically comparing the simulated signals with
      corresponding signals obtained from a previous in vivo study. To verify that the
      simulated signals can be classified correctly we have applied a classification
      technique based on an artificial neural network. The acoustic features extracted
      from the spectrum over a 2.5 MHz bandwidth are the attenuation coefficient and
      the change of speed of sound with frequency (dispersion). Our results show that
      the algorithm performs satisfactorily. Further testing of the algorithm is
      conducted by the use of a data acquisition and analysis system designed by the
      authors, where several simulated signals are stored in memory chips and
      classified according to their abnormalities.

PMID- 8560632
TI  - [What psychotherapy to offer to anxious patients?].

PMID- 8560633
TI  - [Rubella: epidemiology, diagnosis and prevention].

PMID- 8560634
TI  - [Terbinafine (Lamisil)].

PMID- 8560635
TI  - [Legionnaires' disease in East districts. A retrospective study (1979-1992)].

PMID- 8560636
TI  - [Treatment of essential tremor].

PMID- 8560637
TI  - [Long-term use of neuroleptics].

PMID- 8560638
TI  - [Understanding the treatment of migraine].

PMID- 8560639
TI  - [New antidepressive agents].

PMID- 8560640
TI  - Evaluation of urethral strictures and associated abnormalities using high
      resolution and color Doppler ultrasound.
AB  - OBJECTIVES: To study the role of urethral sonography and color Doppler imaging in
      the evaluation of patients with urethral strictures and associated abnormalities.
      METHODS: We reviewed our experience with 41 urethral sonographic studies in 35
      patients and compared them to 33 retrograde urethrograms. For 6 recent cases, we
      also used color Doppler imaging to assess spongiosal tissue blood flow and the
      location of urethral arteries. RESULTS: Both retrograde urethrography and
      urethral sonography assessed the caliber and length of the strictures well.
      Urethral sonography provided additional information about stricture involvement
      of the spongiosum, location of urethral arteries, and associated abnormalities
      (that is, periurethral abscess and urethrocutaneous fistula). This information
      was useful for the clinical stratification of urethral stricture disease and the
      planning of treatment. CONCLUSIONS: With the advantages of avoiding radiation to
      testis, providing real-time evaluation of the distensibility of the urethra, and
      having the capacity of assessing spongiosum and periurethral tissue involvement
      and urethral artery location, urethral sonography appears to offer more than
      retrograde urethrography for the evaluation of anterior urethral stricture.

PMID- 8560641
TI  - Mohs' micrographic surgery and distal urethrectomy with immediate urethral
      reconstruction for glanular carcinoma in situ with significant urethral
      extension.
AB  - OBJECTIVES: To report the use of conservative extirpative surgical techniques to
      manage glanular carcinoma in situ with significant urethral extension. METHODS:
      Over a 5-year period, 2 patients with carcinoma in situ of the glans with
      significant distal urethral involvement, who refused penectomy, were managed with
      combined treatment modalities using Mohs' micrographic surgery and distal
      urethrectomy with immediate urethral reconstruction. RESULTS: At follow-up of 5
      years and of 12 months, there has been no evidence of meatal or proximal urethral
      recurrence. CONCLUSIONS: Mohs' micrographic surgical excision and distal
      urethrectomy with immediate urethral reconstruction offers an acceptable
      alternative to partial penectomy in patients with perimeatal carcinoma in situ
      who fail conservative treatment or refuse penectomy.

PMID- 8560642
TI  - Isolated ureteral injury caused by blunt trauma.
AB  - OBJECTIVES: Ureteral injury is rare after blunt trauma. Herein is presented this
      unusual scenario of ureteral trauma in addition to the pathophysiology of this
      injury. METHODS: A 12-year-old boy sustained a rupture of the right ureter 6 cm
      below the ureteropelvic junction after a car accident. No other injuries or
      fractures were identified. RESULTS: Ureteral injury was immediately diagnosed and
      repaired primarily. Intravenous urography performed 8 weeks after surgery
      revealed normal ureteral healing without stricture formation. CONCLUSIONS: To our
      knowledge, the isolated avulsion of the ureter in this location has not been
      reported previously, but must be considered in those patients with severe blunt
      trauma and hyperextension injuries.

PMID- 8560643
TI  - Prenatal diagnosis of genital anomalies.
AB  - OBJECTIVES: This is a report of five cases of abnormal fetal genitalia detected
      by routine prenatal ultrasound. METHODS: Retrospective review was conducted to
      identify all cases of abnormal fetal genitalia identified by routine obstetrical
      ultrasound at our institution in which postpartum follow-up was available.
      RESULTS: Five cases of prenatal sonographically diagnosed abnormal fetal
      genitalia were confirmed postnatally. The abnormalities include ambiguous
      genitalia, severe hypospadias with unilateral cryptorchidism, megalourethra, and
      concealed penis. In all cases, other anomalies were discovered during the
      prenatal ultrasound. CONCLUSIONS: Prenatal ultrasound may detect a variety of
      abnormalities of the fetal genitalia.

PMID- 8560644
TI  - Endoscopic intrauterine fetal therapy: a monkey model.
AB  - OBJECTIVES: Prenatal ultrasonographic investigations have led to an increasing
      number of prenatally detected abnormalities, of which a large number involves the
      urogenital tract. This study was performed to evaluate if endoscopic intra
      amniotic access is possible in primates. METHODS: In 10 midtrimester rhesus
      monkeys (Macaca mulatta), endoscopic intrauterine fetoscopy was performed with
      three access cannulas. Using a Seldinger technique, a vascular access system, and
      a pediatric laparoscopy set, intra-amniotic inspection was attempted. Fetal
      growth throughout pregnancy was monitored by ultrasonographic measurements of
      fetal biometry. RESULTS: Intrauterine access could successfully be achieved in 10
      rhesus monkeys with three cannulas. After partial amniotic fluid exchange,
      adequate fetoscopy was always possible. Two monkeys aborted on the second and
      sixth postoperative days. Serial ultrasonographic investigations for fetal
      biometry showed no disturbance of the intrauterine growth patterns in the
      remaining 8 monkeys. CONCLUSIONS: We currently conclude that the rhesus monkey
      model for experimental intrauterine endoscopic surgery may be suitable for study
      of the developmental abnormalities of the genitourinary tract.

PMID- 8560645
TI  - Technique of radical cystectomy and simultaneous repair of an abdominal aortic
      aneurysm.
AB  - Surgical repair of an abdominal aortic aneurysm in conjunction with radical
      cystectomy and orthotopic urinary diversion can be safely performed without
      morbidity secondary to excessive blood loss, operative time, or vascular graft
      infection. The techniques required for this combined procedure and a case report
      are discussed.

PMID- 8560646
TI  - A simplified method of epididymal sperm aspiration.
AB  - We present a simple technique of epididymal sperm aspiration that uses
      inexpensive and readily available materials. Men undergoing epididymal
      reconstruction with vasoepididymostomy or autogenous sperm reservoir had sperm
      aspiration for cryopreservation. Mean total and total motile sperm per aspirate
      recovered from 25 men have been 25.1 +/- 4.8 x 10(6) and 4.0 +/- 1.4 x 10(6),
      respectively. Two ongoing pregnancies have been achieved with intracytoplasmic
      sperm injection using thawed epididymal sperm. Sperm aspiration and
      cryopreservation maximize a couple's fertility potential with a single procedure
      and provide a viable fertility alternative to a second surgical procedure in the
      event of a primary reconstructive failure.

PMID- 8560647
TI  - Renal cell carcinoma with caval extension to the heart.

PMID- 8560648
TI  - Bilateral emphysematous pyelonephritis: a case report and review of the
      literature.
AB  - Emphysematous pyelonephritis is a rare, rapidly progressive, life-threatening
      infection of the renal parenchyma. It most commonly is unilateral, is found
      almost exclusively in diabetics, is associated with gas-forming coliform
      bacteria, and is characterized by the presence of gas within the renal
      parenchyma. Early aggressive therapy (combined medical and surgical) is the
      hallmark of successful treatment. A high index of suspicion coupled with
      radiographic imaging is essential to make a timely diagnosis and guide
      therapeutic intervention. Bilateral emphysematous pyelonephritis is an even more
      rare phenomena, with only 14 reported cases in the English literature and is
      associated with a high patient mortality. We herein present an additional case
      and review the literature as it pertains to bilateral emphysematous
      pyelonephritis. Appropriate care requires aggressive combined medical and
      surgical therapy in an attempt to preserve renal function without increased
      mortality.

PMID- 8560649
TI  - Ureteral bladder augmentation using the lower pole ureter of a duplicated system.
AB  - Megaureters of nonfunctioning renal segments in a duplex system are commonly
      available for use in reconstructive procedures secondary to high-grade reflux,
      ectopic ureter, ectopic ureterocele, or obstructive megaureter. The use of
      megaureters subtending a nonfunctioning lower pole renal segment for bladder
      augmentation in 2 patients is reported.

PMID- 8560650
TI  - Ileal-ileal intussusception: an unusual complication following enterocystoplasty.
AB  - Postoperative ileal-ileal intussusception is an unusual and uncommonly cited
      complication of bladder augmentation. The preoperative diagnosis is difficult due
      to the vague clinical findings. We report a case of ileal-ileal intussusception
      that occurred following gastrocystoplasty in a child. Computed tomography
      accurately diagnosed the condition preoperatively, and led to early exploratory
      laparotomy and successful reduction.

PMID- 8560651
TI  - Computer modeling in urology.

PMID- 8560652
TI  - Delayed infection of a pelvic lymphocele following pelvic lymphadenectomy.
AB  - Pelvic lymphocele is an infrequent complication of pelvic surgery, usually
      presenting shortly after surgery. We report a case of an infected pelvic
      lymphocele presenting more than 1 year after a staging pelvic lymphadenectomy for
      adenocarcinoma of the prostate. This case illustrates that late infection of
      pelvic lymphoceles can occur following a pelvic lymphadenectomy and radical
      prostatectomy.

PMID- 8560653
TI  - Osteomyelitis secondary to an osteoenteric fistula.
AB  - Osteomyelitis involving the symphysis pubis is a rare complication of pelvic
      surgery, and differentiation with osteitis pubis may be difficult. Herein we
      present a case of a patient in whom a disabling public pain developed 4 months
      after a radical cystectomy for bladder cancer. His pain was unresponsive to
      medical and antibiotic therapy and subsequently proved to be caused by public
      osteomyelitis secondary to a small-bowel fistula precipitated by cancer
      recurrence.

PMID- 8560654
TI  - Neurogenic erectile dysfunction: the course of nicotinamide adenine dinucleotide
      phosphate diaphorase-positive nerve fibers on the surface of the prostate.
AB  - OBJECTIVES: Nitric oxide (NO) plays an important role as a neurotransmitter in
      the peripheral neural regulation of erection. A histochemical stain able to
      localize fibers releasing NO in combination with an in vivo study were used to
      evaluate the course and physiologic significance of the nerve fibers innervating
      the cavernous smooth muscle. METHODS: Morphologic studies in 6 rats and 6 human
      cadavers were performed, tracing the course of branches of the cavernous nerve
      branches using a nicotinamide adenine dinucleotide phosphate diaphorase staining
      technique. Electrostimulations in rats were performed before and after
      transection of the anterolateral part of the prostate capsule. RESULTS: Multiple
      nerve fibers were documented running on the lateral and ventral surfaces of the
      prostate distinct from the classically described dorsolateral neurovascular
      bundle. Transection of these fibers resulted in a loss of electrically induced
      intracavernous pressure (59.4 +/- 5.6 cm H2O versus 27.0 +/- 4.6 cm H2O).
      CONCLUSIONS: These preliminary morphologic and physiologic studies support a
      significant role for these nerve fibers in erection.

PMID- 8560655
TI  - Economic modeling to assess the costs of treatment for benign prostatic
      hyperplasia.

PMID- 8560656
TI  - Practical biomedical statistics: a guide to the selection of statistical tests.

PMID- 8560657
TI  - Same day surgery for radical retropubic prostatectomy: is it an attainable goal?
AB  - OBJECTIVES: Economic forces are stimulating a re-evaluation of various management
      strategies. Recent critical pathways for radical prostatectomy have resulted in
      reduced length of stay to as low as 2.9 days. METHODS: The time in the operating
      room and recovery room, average blood loss, length of hospitalization, patient
      charges, and estimated hospital costs were compared for 20 patients undergoing
      radical prostatectomy up to 1 year before and for 27 men after initiation of a
      critical pathway. Under the protocol, patients receive an education booklet and
      preoperative teaching in preparation for early discharge and an epidural for
      anesthesia. An anonymous questionnaire was mailed to all patients treated by the
      pathway after catheter removal. RESULTS: The new pathway resulted in a
      significant reduction in average time in the operating room (3.7 +/- 0.4 hours
      versus 4.9 +/- 1.2 hours), estimated blood loss (1204 +/- 527 cc versus 1948 +/-
      740 cc), and length of hospitalization (1.7 +/- 0.6 days versus 4.6 +/- 1.5
      days). In addition, patient charges and hospital costs were reduced by 32% and
      35%, respectively. Thirty-seven percent of the study group was discharged after 1
      night compared with 0% in the group treated before the pathway was initiated.
      Forty-one percent of the study group was not transfused and did not donate blood.
      Outcome surveys completed by 25 of 27 study patients revealed an overall
      satisfaction of 96% with 0 of 10 patients who were discharged after one night
      indicating they would have preferred to be hospitalized longer. CONCLUSIONS:
      Conventional management of men undergoing radical prostatectomy can be safely
      modified while preserving patient satisfaction without increasing morbidity.
      Avoiding peripheral narcotics and emphasizing preoperative teaching has enabled
      us to reduce length of stay greatly, with same day discharge now an attainable
      goal.

PMID- 8560658
TI  - Transforming growth factor-alpha expression in human renal cell carcinoma: TGF
      alpha expression in renal cell carcinoma.
AB  - OBJECTIVES: To characterize the expression of transforming growth factor-alpha
      (TGF-alpha) in various histologic types of renal cell carcinomas. METHODS:
      Immunohistochemistry of renal cell carcinoma and adjacent normal tissue was
      performed on formalin-fixed tissue using a specific monoclonal antibody to TGF
      alpha. RESULTS: Clear and distinct staining was present in normal distal
      convoluted tubules and collecting ducts. The growth factor was not observed in
      the glomerulus or the proximal tubule. In tumors composed of clear cells,
      staining was evident only in endothelial cells but not in the tumor cells
      themselves. In granular cell type tumors, the tumor cells as well as endothelial
      cells stained for TGF-alpha. When mixed cell type tumors were studied, a
      heterogenous pattern of growth factor expression was found. Endothelial cells and
      granular cells but not clear cells demonstrated positive staining. CONCLUSIONS:
      These studies suggest that TGF-alpha is likely to play a major role in
      neovascularization of clear cell carcinomas and that the growth factor may be
      more important in supporting proliferation of granular cell type tumors.

PMID- 8560659
TI  - Prognostic value of urokinase-type plasminogen activator in patients with
      superficial bladder cancer.
AB  - OBJECTIVES: A number of studies have demonstrated that urokinase-type plasminogen
      activator (u-PA) is one of the major enzymes in the development of cancer
      invasion and metastasis. We examined the possibility that u-PA content is an
      independent prognostic marker for superficial bladder cancer. METHODS: The u-PA
      content was estimated in superficial bladder cancer from 52 patients undergoing
      transurethral resection for the first time. The survival rates of the patients
      were calculated and the prognostic values for u-PA content (less than 8 ng/mg
      protein versus more than 8 ng/mg), Stage (pTa or pT1), grade (1 and 2 versus 3),
      number (single versus multiple), and size (less than 1 cm versus more than 1 cm)
      of tumor were determined by a multivariate regression model. RESULTS: Development
      of cancer invasion and metastasis was observed in 3 and 8 patients, respectively.
      The survival rate of the patients with high u-PA content was significantly lower
      than those with low u-PA content (P < 0.005). In the multivariate regression
      analysis, u-PA content was the most important risk factor for the prognosis,
      compared with the other factors: tumor stage, grade, multiplicity, and size.
      CONCLUSIONS: We have first shown that u-PA content is a new independent
      prognostic marker in patients with superficial bladder cancer.

PMID- 8560660
TI  - Comparison of the cellular composition of benign prostatic hyperplasia in Chinese
      and Caucasian-American men.
AB  - OBJECTIVES: To compare the cellular composition of benign prostatic hyperplasia
      (BPH) in Chinese and Caucasian-American men. METHODS: Surgical specimens of the
      prostate were obtained from 9 Chinese and 8 Caucasian-American men undergoing
      cystoprostatectomy for invasive transitional cell carcinoma. The mean ages of the
      Chinese and Caucasian-American men were 66.8 years and 66.4 years, respectively
      (P = 0.94). The mean prostate weight of the Chinese and Caucasian-American men
      was 53.4 g and 32.1 g, respectively (P = 0.01). Double immunoenzymatic staining
      with antibodies against actin and prostatic acid phosphatase and computer
      assisted color image analysis were performed on whole-mount tissue sections. The
      percent area density of smooth muscle (SM), connective tissue (CT), epithelium
      (E), and epithelial lumen (L) were obtained by analyzing 30 fields from each
      specimen. RESULTS: The mean percent area density of SM, CT, E, and L in the
      prostate of Chinese men was 32%, 9.1%, 10.8%, and 48.5%, respectively. The mean
      percent area density of SM, CT, E, and L in the prostate of Caucasian-American
      men was 52.5%, 27.9%, 12.8%, and 7%, respectively. Overall, the prostates of
      Chinese men contained significantly more glandular lumen and significantly less
      SM and CT. CONCLUSIONS: The present study demonstrates that the cellular
      composition of BPH in the prostates of Caucasian-American and Chinese men is
      different. These cellular differences may account for previously observed
      differences in the incidence of clinical BPH.

PMID- 8560661
TI  - The Oxford Laser Prostate Trial: sensitivity to change of three measures of
      outcome.
AB  - OBJECTIVES: To evaluate the sensitivity to change of outcome measures in a double
      blind randomized controlled trial of transurethral resection of the prostate
      (TURP) and contact laser prostatectomy. METHODS: A total of 152 patients were
      randomized to TURP or contact laser prostatectomy using the Surgical Laser
      Technology (SLT) system. Preoperative data were obtained using a self
      administered questionnaire containing the American Urological Association (AUA-7)
      symptom score, the bothersome score (benign prostatic hyperplasia impact index),
      and the Short Form-36 health status questionnaire (SF-36). Follow-up was at 1 and
      3 months. Effect size scores were calculated to indicate the extent of change
      from baseline to follow-up. RESULTS: Data were available on 148 patients: 72
      received laser therapy and 76 received TURP. Mean change in AUA-7 score at 3
      months was 7.3 in the laser arm, compared with 11.9 in the TURP arm (P < 0.05).
      Furthermore, substantial change was detected in both groups on the bothersome
      score. However, very few significant differences in SF-36 dimension scores from
      baseline to 3 months were detected. CONCLUSIONS: The SF-36 at both baseline and
      follow-up indicated a similar level of health status as that reported in the
      general population. Subsequently, the measure did not improve on any dimensions.
      Our data support the claim of some researchers that shorter disease-specific
      indices are vital to the evaluation of treatment regimens in clinical trials,
      especially when the general health of the patients is similar to that of the
      population.

PMID- 8560662
TI  - Holmium laser resection of the prostate: preliminary results of a new method for
      the treatment of benign prostatic hyperplasia.
AB  - OBJECTIVES: To assess the early efficacy and safety of holmium laser resection of
      the prostate (HoLRP) for the treatment of patients with symptomatic benign
      prostatic hyperplasia (BPH). METHODS: The initial 84 patients undergoing HoLRP at
      this institution are reported. All patients underwent standard urologic
      evaluation for BPH with American Urological Association (AUA) symptom score, peak
      urinary flow rate (Qmax), ultrasound prostate volume estimation, prostate
      specific antigen and digital rectal examination. The patients were reassessed at
      1 month (72 patients) and 3 months (48 patients) postoperatively. The resection
      time, total operating time, holmium energy used (kilojoules), catheter time, and
      hospital stay were all recorded. RESULTS: The mean patient age was 65.3 years (49
      to 80). The mean AUA score improved from 21.3 preoperatively to 7.6 at 1 month
      and 4.1 at 3 months. The mean Qmax likewise increased from 7.5 mL/s
      preoperatively to 17.8 mL/s at 1 month and 19.3 mL/s at 3 months. Two patients
      (2%) required bladder irrigation for heavy hematuria perioperatively and 4
      patients (5%) required recatheterization. Few patients experienced irritative
      urinary symptoms and to only a mild degree. CONCLUSIONS: The technique of HoLRP
      produces a cavity identical in appearance to transurethral resection of the
      prostate. It is a relatively bloodless procedure that results in a short catheter
      time, immediate symptomatic improvement, and minimal postoperative irritative
      symptoms. The short-term results are excellent but longer-term follow-up is
      necessary.

PMID- 8560663
TI  - Transurethral fulguration of the prostate with the roller ball.
AB  - OBJECTIVES: To assess the histologic changes in the prostate and the clinical
      outcome in men with symptomatic benign prostatic hyperplasia (BPH) following
      transurethral fulguration of the prostate (TUFP) with the roller ball. METHODS:
      The study was conducted in two phases. In the first phase of the study,
      histologic changes in the prostate following fulguration with the roller ball
      were studied in 10 men with BPH who were already scheduled for transurethral
      resection of the prostate (TURP). In the second phase of the study, 20 male
      patients with symptomatic BPH underwent TUFP with the roller ball. All patients
      had preoperative assessment with history and physical examination, urinalysis,
      uroflow, transrectal ultrasound of the prostate, serum prostate-specific antigen,
      serum hemoglobin and electrolytes, and cystoscopy. The procedure was performed
      under general or spinal anesthesia using standard equipment and 3-mm roller ball.
      The patients were seen in follow-up at 1, 3, 6, 9, and 12 months. RESULTS: The
      results of the first phase of the study indicate that the coagulating current
      results in thermal destruction of prostatic tissue in the form of coagulative
      necrosis with minimal if any vaporization. The cutting current results in tissue
      vaporization with minimal coagulative necrosis. Twenty men have enrolled in the
      second phase of the study. Their mean age is 63.2 +/- 7.5 years and their mean
      follow-up is 4.6 months (range, 1 to 12). Their mean American Urological
      Association (AUA) symptom score declined from 22.9 +/- 4.2 preoperatively to 6.4
      +/- 4.9, 5.3 +/- 3.2, 4.3 +/- 1.9, 6 +/- 2.9, and 9 at 1, 3, 6, 9, and 12 months,
      respectively. The mean maximum flow rate (Qmax) increased from 8.9 +/- 3.4 mL/s
      preoperatively to 24.3 +/- 1.9 mL/s at 3 months, 22 +/- 4.4 mL/s at 6 months,
      17.6 +/- 5 mL/s at 9 months, and 21 mL/s at 12 months postoperatively. The mean
      prostate volume was 31.9 +/- 10 mL and the mean operative time was 44.9 +/- 10
      minutes. No significant changes were seen in serum hemoglobin and serum sodium.
      The mean hospital stay was 0.7 day (0 to 2). Nineteen patients had their
      catheters removed within 24 hours and 1 patient had his catheter removed 48 hours
      postoperatively. No patient experienced impotence, incontinence, urethral
      stricture, post-transurethral resection syndrome, or required blood transfusion.
      In 1 patient (5%) bladder neck stenosis developed at 9 months and 1 patient
      required TURP for residual apical adenoma at 3 months. CONCLUSIONS: The nature
      and the degree of tissue changes in the prostate following fulguration with the
      roller ball are well controlled and predictable. When the cutting current is
      used, prostatic tissue can be removed safely and effectively. The clinical
      outcome after TUFP with the roller ball demonstrates significant improvement in
      subjective (AUA symptom score) and objective (Qmax) parameters, with reduced
      morbidity and short hospital stay. These early results compare favorably with
      those seen after TURP and laser ablation of the prostate. Larger series with
      longer follow-up are necessary to establish the long-term efficacy of TUFP in the
      treatment of BPH.

PMID- 8560664
TI  - Variability of repeated serum prostate-specific antigen (PSA) measurements within
      less than 90 days in a well-defined patient population.
AB  - OBJECTIVES: To determine the variability of repeated serum prostate-specific
      antigen (PSA) measurements within less than 90 days in a well-defined patient
      population. METHODS: A retrospective review of the PSA database at the Dallas
      Veterans Affairs Medical Center in Dallas was performed to identify patients who
      had two serum PSA measurements within less than 90 days, with the first PSA being
      less than 10 ng/mL (monoclonal assay, Abbott IMx). Patients' age and the dates
      and results of the PSA 1 and 2 measurements were captured in a database. Charts
      were reviewed on all patients, and those who had undergone a manipulation likely
      to alter the PSA value either before PSA 1 or between the two PSA measurements
      were excluded. The results of digital rectal examination (DRE) were classified as
      follows: no pathologic condition, benign prostatic hyperplasia, or suspected
      carcinoma of the prostate. The data were stratified in a variety of ways and
      analyzed to determine the variability of repeated PSA measurements under varying
      conditions. RESULTS: A total of 295 men were identified who fulfilled the
      conditions. Mean age was 66.3 +/- 8.3 (standard deviation [SD]) years, and the
      mean PSA 1 was 2.7 +/- 2.4 (SD) ng/mL. When stratified by whether PSA 1 was 4.0
      or less or from 4.1 to 10.0 ng/mL, the mean values (1.41 versus 1.43 and 6.00
      versus 5.89 for PSA 1 and 2, respectively) were not significantly different.
      Similarly, when stratified by whether PSA 2 was obtained within 30 days, 30 to 60
      days, or 60 to 90 days, there was no significant difference between the mean
      values for PSA 1 and 2. When stratified by decade of life, there were no
      differences between PSA values for any decade, although a clear relationship was
      seen between mean PSA and age (less than 50 years: 1.39 versus 1.06; 50 to 60
      years: 1.89 versus 1.70; 60 to 70 years: 2.47 versus 2.48; 70 to 80 years: 3.65
      versus 3.70; more than 80 years: 3.45 versus 3.56). A stratification by results
      of the DRE (1 = normal, 2 = benign prostatic hyperplasia, 3 = prostate cancer
      suspected) yielded the following values: DRE 1: 2.40 versus 2.47; DRE 2: 2.99
      versus 2.75; DRE 3: 3.64 versus 3.81; the difference was not significant for all
      three groups. Forty-six percent of patients either had an identical PSA or an
      increase in the PSA, and 54% had a decrease. One third of the patients had a
      difference of greater than +/- 1.0 ng/mL. The largest differences noted were -5.3
      and +7.5 ng/mL. Cumulative distributions of differences were calculated, and the
      patients were stratified by time intervals, age, DRE findings, and PSA 1 values.
      With the exception of the latter, there were no significant differences noted in
      the other three stratifications. CONCLUSIONS: There is a significant variability
      between two serum PSA measurements obtained within a short-time interval, which
      is due to chance alone. These results highlight the problem when relying on a
      single PSA measurement and using either a single cutoff, age-specific reference
      ranges, or a rate of change to trigger further diagnostic tests, such as a
      biopsy. Furthermore, they raise the question whether two measurements and in case
      of discrepancy a third measurement should precede any further recommendation or
      invasive testing. Decision aids are offered to physicians to select ranges of PSA
      within which they may wish to repeat a PSA test, depending on calculated
      probabilities for the second PSA to cross the predefined cutoff value.

PMID- 8560665
TI  - Quality of life of persons with urinary incontinence: development of a new
      measure.
AB  - OBJECTIVES: Our objective was to develop a self-report quality of life measure
      specific to urinary incontinence (I-QOL) that could be used as an outcome measure
      in clinical trials and in patient care centers. METHODS: The I-QOL was developed
      from interviews of 20 individuals with urinary incontinence. Refining the
      questionnaire was accomplished by structured interviews of 17 individuals with
      urinary incontinence. Testing the I-QOL's psychometric properties involved two
      administrations (n = 62) along with measures of psychologic well-being and
      functional status. RESULTS: The rigorous development process ensured that the
      measure was complete and understandable. The I-QOL proved to be internally
      consistent (alpha 0.95) and highly reproducible (r = 0.93; 18 days; SD 4). For
      discriminant validity, severity of incontinence (P < 0.0001) and number of
      medical appointments in the past year to treat incontinence (P < 0.0001)
      significantly predicted I-QOL scores. Convergent validity analyses confirmed our
      predictions that the I-QOL scores were more closely related to overall well-being
      than bodily pain. CONCLUSIONS: The I-QOL proved to be valid and reproducible as a
      self-administered measure for assessing quality of life of patients with urinary
      incontinence.

PMID- 8560666
TI  - Incidence of varicoceles in men with primary and secondary infertility.
AB  - OBJECTIVES: To determine whether varicoceles are more prevalent in men with
      secondary infertility than in men with primary infertility. METHODS: The records
      of 2188 consecutive men attending three infertility centers were reviewed to
      determine the incidence of varicoceles in men with primary and secondary
      infertility. In addition, other factors affecting both male and female
      infertility were assessed in these patients. RESULTS: The incidence of
      varicoceles was not significantly different between the 1447 men with primary
      infertility versus the 741 men with secondary infertility: 44% and 45%,
      respectively. The incidence of vasal agenesis was significantly greater in men
      with primary infertility (P < 0.001). In addition, the female partner was
      significantly older in couples with secondary infertility (P < 0.001).
      CONCLUSIONS: These findings do not support the conclusion that varicoceles have a
      progressive adverse effect on fertility over time and suggest that further study
      is needed to determine whether varicocele repair is indicated in patients with
      normal semen parameters.

PMID- 8560667
TI  - Sperm kinematics of cryopreserved normozoospermic specimens after artificial
      stimulation.
AB  - OBJECTIVES: Cryopreservation of semen is associated with reduced motility after
      thawing, resulting in a decreased pregnancy rate. Artificial stimulation of
      motility has been used in fresh semen samples. This study measured the effect of
      motility stimulants on various motion characteristics and other sperm functions
      using cryopreserved semen. METHODS: Frozen semen samples from healthy donors were
      thawed, and motility stimulants were added in vitro and incubated for 60 minutes.
      The percentages of motile spermatozoa in each specimen and other motion
      characteristics were measured. In addition, spermatozoon's viability, membrane
      integrity, and ability to penetrate bovine cervical mucus were studied after
      addition of stimulants. RESULTS: Percentage motility and all other motion
      characteristics improved after stimulation with pentoxifylline, caffeine, or 2
      deoxyadenosine. Linearity did not significantly differ in the control samples
      after adding any of the stimulants. Viability, membrane integrity, and
      penetration ability did not improve significantly and were comparable with
      control values. CONCLUSIONS: Pentoxifylline, caffeine, and 2-deoxyadenosine can
      stimulate sperm motility and other motion characteristics. This may be beneficial
      in the cryopreservation of sperm from normal donors and oligozoospermic patients
      for use in assisted reproduction.

PMID- 8560668
TI  - Testicular cancer in association with developmental renal anomalies and
      hypospadias.
AB  - OBJECTIVES: To characterize the clinical, pathologic, and genetic aspects of
      patients with a previously undescribed phenotype of testicular germ cell tumors
      associated with renal hypoplasia or agenesis and urethral hypospadias. METHODS:
      Review of clinical and pathologic findings and genetic analysis of constitutional
      and tumor DNA for mutations of the Wilms' tumor suppressor gene (WT1). RESULTS:
      Clinical findings suggest that this phenotype is distinct from other syndromes
      associated with renal anomalies and that the associated testicular tumors are
      histologically and clinically similar to those that occur sporadically. No
      karyotypic abnormalities, loss of heterozygosity, or mutations in the zinc finger
      domains (exons 7-10) of WT1 were observed in 5 patients with this phenotype.
      CONCLUSIONS: The phenotype of testicular germ cell tumor, developmental renal
      anomalies, and urethral hypospadias constitutes a discrete syndrome caused by a
      gene distinct from WT1.

PMID- 8560669
TI  - Surgical treatment of penile veno-occlusive dysfunction: is it justified?
AB  - OBJECTIVES: Veno-occlusive dysfunction is a commonly diagnosed cause of
      impotence. Surgical removal of the intermediate (deep dorsal vein and its
      tributaries) venous system of the penis has been advocated as an effective
      treatment but recurrence of the dysfunction is common after a few months. We
      studied prospectively the first 100 cases of veno-occlusive dysfunction
      undergoing surgical treatment at our institutions. METHODS: One hundred
      consecutive patients undergoing penile venous ligation surgery were evaluated.
      All patients had a comprehensive workup prior to therapy. Surgery involved
      excision of the intermediate venous drainage. Short-term results were
      investigated by personal interview, and long-term outcome was determined by
      separate telephone interview of patients and their partners when available.
      RESULTS: Short-term success (3 months) was 62%, and long-term success (45 months)
      was 31%. Historical factors, preoperative testing results, and histologic
      assessment of the surgical specimens were not found to be helpful in predicting
      outcome. CONCLUSIONS: Despite the mediocre long-term results of the surgical
      procedure and lack of preoperative predictive factors, we believe that venous
      leak surgery could be offered to well-selected patients in whom the only other
      available alternative would be a prosthetic device.

PMID- 8560670
TI  - 7-Nitroindazole: a selective inhibitor of penile erection: an in vivo study in a
      rat animal model.
AB  - OBJECTIVES: The neuronal isoform of nitric oxide synthase (nNOS) has been
      localized in neurons innervating the penis and is believed to be an important
      mediator of erection. Using the selective inhibitor 7-nitroindazole (7-NI), we
      evaluated the possible role of nNOS in penile erection using a rat animal model.
      METHODS: Eighteen Sprague-Dawley rats were divided into three study groups. A
      sham group (n = 6) received the vehicle arachis oil, a low-dose group received 5
      mg/kg (n = 6), and a high-dose group received 50 mg/kg (n = 6) of 7-NI prior to
      measurement of blood pressure and cavernous nerve stimulation-induced rise in
      intracavernous pressure. RESULTS: A dose-dependent inhibition of erection by 7-NI
      was seen. Control animals had an intracavernous pressure rise of 55.5 +/- 4.0 cm
      H2O, whereas the low-dose group had 26.5 +/- 2.8 cm H2O and the high-dose group
      had 6.2 +/- 2.1 cm H2O. A partial recovery of erection was seen in the low- and
      high-dose groups after 3 hours. Blood pressure was unaffected by 7-NI
      administration. CONCLUSIONS: 7-NI induced a reversible, dose-dependent inhibition
      of erection without affecting blood pressure. This in vivo study provides further
      evidence of the role played by nNOS in erection.

PMID- 8560671
TI  - Detection of leakage in inflatable genitourinary devices.
AB  - OBJECTIVES: Improved manufacturing techniques and stronger materials have
      significantly reduced but not eliminated the incidence of hydraulic leakage in
      the inflatable genitourinary devices. This study was designed to test the
      efficacy of pressure dissipation and volume loss as potential tests for the
      detection of site-specific hydraulic leakage in the inflatable penile prosthesis
      (IPP) and the artificial sphincter (AS) and compare their efficacy with the
      current standard--the ohmmeter technique. METHODS: Five IPPs and ASs were
      dismantled to achieve five reservoirs and cuff-pump assemblies. Each component
      was inspected visually and then tested for volume, pressure, and electrical
      resistance over 5 minutes. Next a needle puncture was deliberately made in these
      components, and the experiment was repeated. The in vivo pseudocapsule was
      simulated by an elastic covering, made from antiembolic hose. RESULTS: The
      techniques of pressure, volume, and ohmmeter testing were not able to detect
      current leakage in all the components, with the pseudocapsule in place.
      CONCLUSIONS: None of the currently available tests qualify for the label of "gold
      standard" in accurately detecting hydraulic leakage. We currently recommend
      testing the device's integrity by visual inspection in vivo, starting with the
      reservoirs. If a leakage is detected, the reservoir alone is replaced. If no
      leakage is found, we recommend that the entire unit be removed and replaced. If
      the malfunctioning device is more than 2 years old, we suggest that it be
      entirely replaced.

PMID- 8560672
TI  - Bicalutamide (Casodex): The Critical Issues 1996. Proceedings of a meeting.
      Boston, Massachusetts, July 6-9, 1995.

PMID- 8560673
TI  - The preclinical development of bicalutamide: pharmacodynamics and mechanism of
      action.
AB  - OBJECTIVES. To describe the preclinical development of bicalutamide and clarify
      its pharmacodynamics and mechanisms of action. Bicalutamide was developed from a
      series of nonsteroidal compounds related to flutamide that showed a range of
      pharmacologic activity from full androgen agonist to pure antiandrogen, including
      progestational and antiprogestational properties. METHODS AND RESULTS.
      Bicalutamide is a pure antiandrogen that binds to rat, dog, and human prostate;
      the affinity compared with the natural ligand 5 alpha-dihydrotestosterone is low,
      but bicalutamide has an affinity for the rat androgen receptor approximately four
      times higher than hydroxyflutamide, the active metabolite of flutamide.
      Bicalutamide also binds to androgen receptors found in the LNCaP human prostate
      tumor and the Shionogi S115 mouse mammary tumor cell line, as well as androgen
      receptors transfected into CV-1 and HeLa cells. In all cases, bicalutamide
      behaves as a pure antiandrogen and inhibits gene expression and cell growth
      stimulated by androgen. Studies with the LNCaP cell line are particularly
      interesting, as these cells contain a mutated androgen receptor (codon 868, Thr-
      >Ala), which behaves idiosyncratically with other antiandrogens (cyproterone
      acetate and flutamide): both these antiandrogens act as agonists in this cell
      line and stimulate proliferation. Studies in vivo show that bicalutamide is a
      potent antiandrogen in the rat. In immature, castrated male rats treated daily
      with testosterone propionate, bicalutamide produces a profound inhibition of
      accessory sex organ (ventral prostate and seminal vesicles) growth at oral doses
      as low as 0.25 mg/kg; it is more active in this test than flutamide or
      cyproterone acetate. In mature male rats, daily oral doses of bicalutamide
      produce a dose-related reduction in weights of the ventral prostate glands and
      seminal vesicles: in this test, bicalutamide is around five times as potent as
      flutamide. In contrast to flutamide, which produces dose-related, marked
      increases in serum luteinizing hormone (LH) and testosterone as a consequence of
      the central inhibition of the negative feedback effects of androgens on the
      hypothalamic-pituitary-tests axis, bicalutamide has little effect on serum LH and
      testosterone; i.e., it is peripherally selective. The peripheral selectivity of
      bicalutamide in the rat is not due to differences between the prostate versus
      hypothalamic or pituitary receptors, as bicalutamide reverses the suppressive
      effect of testosterone on luteinizing hormone-releasing hormone (LHRH) secretion
      from hypothalamic slices in vitro and is as effective as flutamide at sensitizing
      the pituitary gland to secrete LH in response to administered LHRH. The
      peripheral selectivity of bicalutamide has now been shown to be due to poor
      penetration across the blood-brain barrier: tissue distribution studies with
      [3H]bicalutamide show that although it is concentrated in the organs of
      metabolism and secretion as well as in the prostate, the pituitary glands, and
      the seminal vesicles, levels in the hypothalamus and the central nervous system
      (CNS) are much lower than in blood. Indeed, it is probable that levels found in
      the CNS reflect levels of blood contamination. In dogs, bicalutamide has
      exquisite potency and causes dose-related atrophy of the prostate gland and
      epididymides; with an oral ED50 of 0.1 mg/kg, it is around 50 times as potent as
      flutamide in this species and also more potent than the steroidal antiandrogen
      WIN49596 and the 5 alpha-reductase inhibitor MK-906. Even at substantial
      multiples of the active dose (up to 100 mg/kg orally), bicalutamide failed to
      increase serum testosterone, so it is also peripherally selective in the dog.

PMID- 8560674
TI  - Pharmacodynamics and pharmacokinetics of bicalutamide: defining an active dosing
      regimen.
AB  - Bicalutamide, a potent nonsteroidal antiandrogenic drug devoid of hormonal
      agonist activity, is considered to be a pure antiandrogen. Binding of
      bicalutamide to the androgen receptor results in regression of prostate tumors.
      The antiandrogenic activity resides exclusively in the R-enantiomer. The S
      enantiomer of bicalutamide is rapidly cleared, but the R-enantiomer has a plasma
      elimination half-life of about 1 week, with a tenfold plasma accumulation at all
      dose levels, making it suitable for a once-daily administration. It has been
      shown that plasma concentrations increase linearly with dose after either single
      or multiple dosing. These pharmacokinetics are not affected by age, impairment of
      renal function, or mild-to-moderate hepatic impairment. Following daily
      administration of single doses of 50 mg/day for 12 weeks result in steady-state
      plasma concentrations for the R-enantiomer of +/- 9 micrograms/mL. A single dose
      of 50 mg/day was preferred because this dose resulted in a 50% decrease of
      prostatic acid phosphate (PAP) in 83% of the treated patients. Subsequent studies
      focused on the decrease of prostate-specific antigen (PSA) as a surrogate
      endpoint. Decreases of PSA of > or = 90% were noted with daily doses of 100-200
      mg. The excellent safety profile allows further investigations of doses up to 450
      mg daily. Studies are ongoing to establish the most efficient dose with
      acceptable levels of toxicity in order to maximize the effect of bicalutamide on
      clinical response, time to progression, mortality, and quality of life.

PMID- 8560675
TI  - Hormone therapy for prostate cancer: a topical perspective.
AB  - Evolution of the roles proposed for antiandrogenic agents in prostatic disease
      has been rapid. Since the early suggestions by Labrie and his colleagues that the
      nonsteroidal antiandrogen flutamide could be used in combination with medical or
      surgical castration to provide superior care for patients with metastatic
      prostate cancer, and subsequent substantiation of the theory in a number of
      clinical trials, we have observed an increasing tendency to test the use of
      antiandrogens (alone or in combination with other interventions) earlier in the
      disease process. At least in part, this tendency is a consequence of our
      increased ability to detect prostate cancer earlier in the disease process. At
      the present time, flutamide is the only nonsteroidal antiandrogen available for
      the treatment of prostate cancer in general clinical practice in the United
      States. However, two other nonsteroidal antiandrogens currently await decisions
      on their efficacy and safety by the Food and Drug Administration: nilutamide and
      bicalutamide. Will either of these agents offer clinical benefits beyond those
      offered by flutamide? Will the safety, activity, and dosing profiles of the
      nonsteroidal antiandrogens allow us to use them to treat even earlier stages of
      prostate cancer and perhaps even prostatic intraepithelial dysplasia in patients
      at high risk of prostate cancer? What are the potential future roles for
      bicalutamide and other nonsteroidal antiandrogens in the management of prostatic
      disorders? This article will attempt to lay out the key questions that await
      definitive answers as we expand our understanding of the possible future roles
      for antiandrogens in the management of prostate cancer and related conditions.

PMID- 8560676
TI  - Bicalutamide in the treatment of advanced prostatic carcinoma: a phase II
      multicenter trial.
AB  - OBJECTIVES: The safety, efficacy, and pharmacokinetics of the nonsteroidal
      antiandrogen bicalutamide were investigated in a Phase II trial in 150 patients
      with metastatic prostate cancer. METHODS: Patients took bicalutamide, 50 mg
      daily, in an open-label multicenter North American trial. RESULTS: The objective
      response rate (modified European Organization on Research and Treatment of Cancer
      [EORTC] criteria) was 70% (57% partial, 13% stable); 59 (39%) of 150 patients had
      either a > 90% decrease in prostate-specific antigen (PSA) levels or a decline to
      < 4 ng/mL. Extent of disease on the bone scan was a significant predictor of
      response. Patients with < 6 metastatic lesions were more likely to respond.
      Breast pain and gynecomastia occurred in 76% and 60% of patients, respectively.
      Gastrointestinal toxicity was very infrequent (diarrhea, 5%) The mean drug plasma
      concentration was 8528 (+/- 2928) ng/mL. CONCLUSIONS: Bicalutamide, 50 mg daily,
      was well tolerated and has efficacy in metastatic prostate cancer. The percentage
      of men who had > 90% decline in PSA levels is less than observed with surgical or
      medical castration and has led to trials using this antiandrogen at higher doses
      as monotherapy.

PMID- 8560677
TI  - A controlled trial of bicalutamide versus castration in patients with advanced
      prostate cancer.
AB  - OBJECTIVES: Bicalutamide is a new, potent antiandrogen with potential efficacy in
      the treatment of men with advanced prostate cancer. Although no pure antiandrogen
      has been well studied versus castration, potentially fewer adverse effects could
      occur, making such an agent a potentially useful alternative therapy. To date,
      three randomized controlled trials have been performed comparing these two
      treatments. In preliminary studies, a dose of 50 mg bicalutamide per day was
      selected for these trials. In two of the studies (0302, 0303), this drug was
      compared to either medical or surgical castration, the latter choice being made
      by the patient. In the third study (0301), bicalutamide was compared to bilateral
      orchiectomy. METHODS: Using an intention-to-treat format, the outcomes assessed
      were time-to-treatment failure, time-to-objective disease progression, subjective
      response, and survival time in men with previously untreated metastatic disease.
      The incidence of breast tenderness, gynecomastia, and hot flushes was also
      determined in both treatment arms. A quality-of-life questionnaire was
      administered on multiple occasions after initiation of therapy. RESULTS: Based on
      an analysis of > 1000 patients, the objective and subjective results favored
      castration over bicalutamide (50 mg/day). The hazard ratios for time-to-treatment
      failure (1.59), time-to-disease progression (1.62), and median survival (1.44)
      were all significantly greater in the castration group (P > 0.001). Another
      difference noted at 3 months was a significantly lower median fall in prostate
      specific antigen values in the bicalutamide group (86-88% versus 96-97%).
      Symptomatic patients receiving bicalutamide were only 0.43 times as likely to
      have subjective improvement as the patients treated by castration. A comparison
      of pharmacologic effects showed that only the incidence of hot flushes was lower
      in the bicalutamide group, whereas breast tenderness and gynecomastia were more
      common. This difference in hot flushes, however, translated into better quality
      of life during the first several months with regard to sexual relations and
      sexual functioning. CONCLUSIONS: Bicalutamide monotherapy at 50 mg/day appears
      inferior to castration in overall objective and subjective response rates.
      Whether higher doses of bicalutamide can compete more favorably will need to be
      tested in further clinical trials.

PMID- 8560678
TI  - High-dose bicalutamide monotherapy for the treatment of prostate cancer.
AB  - OBJECTIVES: Bicalutamide is a nonsteroidal competitive inhibitor of androgens at
      the androgen receptor. The level of blockade that can be achieved is dependent on
      the relative numbers of molecules of the agonist and the competitive antagonist
      around the receptor. Increasing the dose of a competitive inhibitor, therefore,
      should potentially increase the level of blockade. Bicalutamide has been
      investigated extensively at daily doses up to 150 mg, and there is evidence of
      increasing blockade at doses up to this point, as evidenced by increasing
      suppression of prostate-specific antigen (PSA) and also improvement in response
      rate, both subjective and objective. At doses of up to 150 mg, increases in
      plasma concentration of bicalutamide were approximately linear, and all doses
      were equally well tolerated. It was thought, therefore, that there was a case for
      investigating higher doses of bicalutamide to determine whether increased
      androgen blockade could be achieved with the use of bicalutamide as monotherapy.
      METHODS: A number of studies have now been carried out evaluating bicalutamide in
      daily doses of 200 mg, 300 mg, and 450 mg. The 200-mg dose has been evaluated as
      a primary treatment for advanced prostate cancer and also as a second-line
      treatment option for patients who have demonstrated a flutamide withdrawal
      response. RESULTS: In noncomparative trials, the decline in PSA value associated
      with daily doses of 200 mg bicalutamide was greater than that observed with daily
      doses of 150 mg, and there was also a slightly higher response rate. When 200 mg
      daily doses were used as therapy following failure of flutamide in combination
      with castration, and also following evidence of a flutamide withdrawal response,
      further responses were seen, perhaps suggesting the theory that in some prostate
      cancer cell mutations, bicalutamide acts as a pure antagonist rather than as a
      partial agonist. More recently, bicalutamide has been evaluated at higher doses:
      20 patients have been exposed for periods up to 6 months at daily doses of 300
      mg. This dose was well tolerated, and evidence of PSA suppression and responses
      were seen that were at least equivalent to those observed at lower doses.
      Pharmacokinetics evaluation has been carried out at this dose, and there is now
      evidence of nonlinearity of plasma concentrations, suggesting that further dose
      escalation is unlikely to confer major additional benefit over the 150- and 200
      mg doses. To confirm the evidence of nonlinearity of plasma concentrations at
      doses > 200 mg, a randomization between 450 mg bicalutamide and medical
      castration is currently being carried out. Patients are still being recruited
      into this trial, but there has been no evidence of any change in the tolerability
      profile of bicalutamide at any dose > 150 mg. CONCLUSIONS: In summary,
      bicalutamide has shown increasing evidence of activity as a competitive blocker
      of the androgen receptor at daily doses of up to 200 mg. At daily doses > 200 mg,
      there is evidence of nonlinearity of plasma concentrations, and therefore further
      benefit is unlikely to be seen as a result of further escalating the dose of
      bicalutamide.

PMID- 8560679
TI  - Maximal androgen blockade for patients with metastatic prostate cancer: outcome
      of a controlled trial of bicalutamide versus flutamide, each in combination with
      luteinizing hormone-releasing hormone analogue therapy. Casodex Combination Study
      Group.
AB  - OBJECTIVES: To review the outcome of therapy with maximal androgen blockade and
      compare the efficacy and safety of bicalutamide and flutamide, each used in
      combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy,
      in patients with untreated metastatic (Stage D2) prostate cancer. METHODS:
      Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x
      2 factorial design. A total of 813 patients were allocated 1:1 to bicalutamide
      (50 mg once daily) or flutamide (250 mg three times daily), plus 2:1 to goserelin
      acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days).
      RESULTS: At the time of analysis (median follow-up, 49 weeks), bicalutamide plus
      LHRH-A was associated with a statistically significant improvement in time-to
      treatment failure, the primary endpoint, when compared with flutamide plus LHRH
      A. The results with longer follow-up (median, 95 weeks) support previous findings
      of an improved time-to-treatment failure with bicalutamide plus LHRH-A; however,
      the difference between groups was not statistically significant. A treatment
      failure endpoint was reached by 68% of patients in the bicalutamide plus LHRH-A
      group, compared with 72% of patients in the flutamide plus LHRH-A group. The
      hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.87 (95%
      confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95%
      confidence limit for survival was 1.00, meeting the definition for equivalence (<
      1.25). With longer follow-up, overall mortality was 34%, with equivalent survival
      between groups: 32% of patients in the bicalutamide plus LHRH-A group died,
      compared with 35% in the flutamide plus LHRH-A group. The hazard ratio of
      bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95% CI, 0.69-1.11; P
      = 0.29). The upper one-sided 95% confidence limit for survival was 1.07, meeting
      the definition for equivalence (< 1.25). Diarrhea occurred in 24% of patients in
      the flutamide plus LHRH-A group compared with 10% of patients in the bicalutamide
      plus LHRH-A group (P < 0.001). CONCLUSIONS: In patients with metastatic prostate
      cancer, bicalutamide plus LHRH-A is effective and well tolerated. Because of its
      efficacy and tolerability profile, together with its convenient once-daily dosing
      formulation, bicalutamide represents a prime candidate for antiandrogen of first
      choice in combination with LHRH-A therapy in the treatment of men with metastatic
      prostate cancer.

PMID- 8560681
TI  - Worldwide activity and safety of bicalutamide: a summary review.
AB  - OBJECTIVES: To evaluate bicalutamide as a therapy in nearly 3000 patients with
      advanced prostate cancer and to determine the dose-ranging, pharmacodynamic, and
      pharmacokinetic properties of bicalutamide. To evaluate bicalutamide as a
      monotherapy or in combination with luteinizing hormone-releasing hormone analogue
      (LHRH-A) therapy. RESULTS: Bicalutamide is a potent, nonsteroidal antiandrogen
      with a plasma half-life consistent with a once-daily schedule. Monotherapy trials
      with 50 mg of bicalutamide established its intrinsic activity, as demonstrated by
      subjective and objective responses and decreases in PSA concentrations. In
      comparison with castration, 50 mg of bicalutamide monotherapy was inferior with
      respect to survival. In a randomized, double-blind (for antiandrogen therapy)
      trial, with a median follow-up of 49 weeks, 50 mg of bicalutamide plus an LHRH-A
      was superior (P = 0.005) to flutamide plus an LHRH-A in delaying time-to
      treatment failure and was better tolerated, as was evident from a significantly
      (P < 0.001) lower incidence of diarrhea and fewer withdrawals for adverse events
      among bicalutamide-treated patients. With longer follow-up and a 34% mortality,
      survival was equivalent between groups. Dose-related effects of bicalutamide on
      serum PSA concentrations were clearly demonstrated in the clinical trial program.
      With a total exposure of > 2800 patient-years, bicalutamide has been shown to be
      a well-tolerated therapy with a low incidence of treatment-related withdrawals.
      CONCLUSIONS: Bicalutamide is a new antiandrogen that offers the convenience of
      once-daily administration, demonstrated activity in prostate cancer, and an
      excellent safety profile. Because it is effective and offers better tolerability
      than flutamide, bicalutamide represents a valid first choice for antiandrogen
      therapy in combination with castration for the treatment of patients with
      advanced prostate cancer.

PMID- 8560680
TI  - Hormone and antihormone withdrawal: implications for the management of androgen
      independent prostate cancer.
AB  - OBJECTIVES: To analyze reported clinical outcomes for patients in whom an agent
      that acts via a steroid hormone receptor was "withdrawn." METHODS: Published
      reports where agent(s) known to act via steroid hormone receptors were
      discontinued in patients with relapsing prostatic cancer were retrieved from
      MEDLINE listings. The trials included patients who progressed on steroidal and
      nonsteroidal antiandrogens, progestational agents, and estrogens. Included were
      the specifics of all treatments administered prior to discontinuation of the
      drugs, concomitant therapies, and factors that might predict a favorable response
      to "withdrawal." RESULTS: Withdrawal responses were observed following the
      discontinuation of the antiandrogens flutamide and bicalutamide, flutamide plus
      aminoglutethimide, estrogens, and progestational agents. In most responding
      cases, responses were seen in patients with long exposure to the drug. No
      specific factors were predictive for response. CONCLUSIONS: Withdrawal responses
      to agents that act via steroid hormone receptors represent a generalized
      phenomenon that can result in palliation for patients with hormonally relapsed
      prostate cancer. A trial of "withdrawal therapy" is warranted in patients with
      relapsing disease prior to the initiation of more toxic therapies. Failure to
      control for this phenomenon in clinical trials may lead to false attribution of
      response to a study agent. The data provide support for the concept that androgen
      independence does not necessarily mean that a tumor is resistant to further
      hormonal manipulations.

PMID- 8560682
TI  - Defining the role of antiandrogens in the treatment of prostate cancer.
AB  - OBJECTIVES: Although antiandrogens have been used as monotherapy and in
      combination with other treatment modalities for management of metastatic prostate
      cancer, their major role to date has been one in which they are used in
      conjunction with surgical or medical castration for treatment of Stage D
      (T4/Nx/M1) carcinoma of the prostate. The widespread use of prostate-specific
      antigen (PSA) is increasing the number of men who are diagnosed with earlier
      stages of this disease, thus resulting in a greater number of definitive
      therapeutic procedures. Also, PSA has become the primary modality for following
      these patients after definitive treatment. Because the use of PSA results in the
      discovery of lower volume of disease and in discerning earlier recurrence of
      disease, the question arises as to whether an antiandrogen alone could be an
      adequate treatment in both neoadjuvant and adjuvant settings. METHODS: As data
      accumulate that point to the efficacy of combined androgen blockade in metastatic
      disease, a protocol has been developed to test the hypothesis of intermittent
      combined treatment in patients who present with minimal disease and good
      performance status. In this study, the antiandrogen bicalutamide will be used in
      combination with the luteinizing hormone-releasing hormone (LHRH) analogue
      goserelin acetate. Also, short-term combined androgen ablation continues to be
      investigated prior to both radiation therapy and radical prostatectomy for
      localized disease. RESULTS: Two groups of patients are ideal candidates for the
      use of antiandrogen monotherapy following radical prostatectomy: those whose PSA
      values do not fall to undetectable levels and the far larger group of men who
      have capsular penetration or positive surgical margins with nondetectable PSA
      levels. Protocols have been developed to assess the clinical potential of
      bicalutamide as the sole adjuvant therapy in these postprostatectomy patients,
      based in no small part on the relative paucity of side effects of this
      antiandrogen. CONCLUSIONS: Antiandrogens in general, and bicalutamide in
      particular, are poised to play an increasing role in the treatment of all stages
      of adenocarcinoma of the prostate. The safety profile of bicalutamide, combined
      with its long half-life, resulting in once-a-day dosing, makes it an ideal choice
      for clinical trials evaluating an antiandrogen, either alone or combined with
      reversible medical castration, in earlier stages of prostate cancer as well as in
      various combination regimens in metastatic disease.

PMID- 8560683
TI  - Mice as carriers of Salmonella enteritidis on persistently infected poultry
      units.
AB  - Evidence of the possible role of wild mice in the epidemiology of Salmonella
      enteritidis infection on broiler breeder and layer breeder units was obtained by
      a bacteriological examination of local mice. Persistent S enteritidis infection
      in birds on these units had been a problem and a high proportion of the mice were
      found to carry salmonella. S enteritidis was isolated from the liver and the
      intestine of most of the mice, indicating a systemic infection. Three-week-old
      chicks were infected by contact with droppings from mice which had been infected
      experimentally with S enteritidis two and five months previously. Wild mice
      infected artificially or naturally excreted S enteritidis intermittently, with up
      to 10(4) organisms in some individual droppings. A naturally infected mouse which
      died after intermittently excreting small numbers of S enteritidis in its
      droppings for 19 weeks had 10(4) organisms/g of liver and 10(3)/g of macerated
      intestine and contents. S enteritidis was also found in fetal tissue in a
      naturally infected mouse suggesting the possibility that the organism might be
      transmitted vertically.

PMID- 8560684
TI  - A review of clinical conditions in pet rabbits associated with their teeth.
AB  - Pet rabbits are frequently treated by veterinary surgeons but most of the
      literature is based on diseases encountered in laboratory or commercial rabbits.
      Many pet rabbits suffer from dental abnormalities and 40 clinical cases of
      diseases associated with teeth problems are reviewed. The clinical and
      radiological examination of the oral cavity of conscious and anaesthetised
      rabbits is described and the treatment of dental disorders is discussed. Post
      mortem studies of 20 of the skulls revealed bone of poor quality. Deformed teeth
      with little or no enamel were found during clinical examination and post mortem.
      The poor quality of the teeth and bone was not related to malocclusion. Distorted
      growth of the crowns led to lacerations to the tongue or inside the cheek,
      causing anorexia, weight loss and problems with grooming. Distorted growth of the
      roots resulted in penetration of the weakened bones of the maxillae, mandibles
      and orbits. Osteomyelitis, abscess formation or infections of the lacrimal duct
      or nasal cavity were a result of this disease process. The cause of the defective
      teeth and poor bone quality was not determined but preventative measures are
      proposed.

PMID- 8560685
TI  - Persistence of bovine herpesvirus-1-specific antibodies in cattle after
      intranasal vaccination with a live virus vaccine.
AB  - To study the development and persistence of circulating antibodies directed
      against bovine herpesvirus-1 (BHV-1) induced by vaccination, approximately 80 per
      cent of the seronegative cows in four partly seronegative dairy herds were
      vaccinated once with a temperature-sensitive live virus vaccine. Most (83 per
      cent) of the vaccinated animals developed antibodies to BHV-1 within two months
      after the vaccination. In the same period, 21 per cent of the unvaccinated
      control cattle also seroconverted, suggesting that the vaccine virus had been
      transmitted to them. Thirty months after they had been vaccinated 91 per cent of
      the vaccinated animals which responded still had detectable antibodies. The
      results suggest that vaccine-induced antibodies may persist for years and thus
      may interfere with control programmes for BHV-1 which are based on serological
      monitoring.

PMID- 8560686
TI  - Mycotic osteomyelitis in a dog following nasal aspergillosis.

PMID- 8560687
TI  - Effect of antibiotic treatment on competitive exclusion against Salmonella
      enteritidis PT4 in broilers.

PMID- 8560688
TI  - Veterinary manpower and 24-hour service.

PMID- 8560689
TI  - Veterinary manpower and 24-hour service.

PMID- 8560690
TI  - Veterinary manpower and 24-hour service.

PMID- 8560691
TI  - Docking of puppies' tails.

PMID- 8560692
TI  - Docking of puppies' tails.

PMID- 8560693
TI  - Docking of puppies' tails.

PMID- 8560694
TI  - Docking of puppies' tails.

PMID- 8560695
TI  - E coli O101 isolated from common seals.

PMID- 8560696
TI  - Veterinary medicines.

PMID- 8560697
TI  - 'Time to stop bleating' about medicines.

PMID- 8560698
TI  - The science and sense behind behaviour counselling.

PMID- 8560699
TI  - Veterinarians and wildlife.

PMID- 8560700
TI  - Portal hypertension associated with primary hypoplasia of the hepatic portal vein
      in dogs.
AB  - Portal hypertension caused by primary hypoplasia of the portal vein was diagnosed
      in 42 dogs. The portal hypertension was manifested by the presence of multiple
      portosystemic collateral vessels. The main clinical signs were retarded growth or
      weight loss, apathy, intermittent diarrhoea and vomiting, anorexia, abdominal
      distension and polydipsia. Major findings at physical examination were ascites in
      23 dogs and neurological signs in 16 dogs. The dogs had increased activities of
      liver enzymes in plasma and increased fasting levels of total bile acids and
      ammonia; in many of the dogs the packed red cell volume, total serum protein and
      albumin were low. Gross inspection of the portal vein revealed a patent but
      underdeveloped extrahepatic vein in 13 of the dogs. Microscopic examination of
      the liver revealed hypoplasia of the intrahepatic portal veins in all the dogs,
      and this was associated with minor arteriolar proliferation and absence of
      fibrosis in 12 of them, with moderate to marked arteriolar proliferation often
      combined with ductular proliferation in 13, and with marked portal fibrosis
      (formerly described as hepatoportal fibrosis) with a varying number of arteriolar
      and bile ductular structures in 17 of the dogs. The disease affected mainly young
      dogs, and was most likely to have been of congenital origin.

PMID- 8560702
TI  - Ultrasonographic evaluation of the jugular vein of cows with catheter-related
      thrombophlebitis.
AB  - Thirty cows with an indwelling jugular catheter developed thrombophlebitis 72
      hours after the insertion of the catheter. The animals with palpable changes of
      the jugular vein, were examined ultrasonographically to reveal the severity and
      extent of the thrombosis. Sixteen cows had mild to moderate thrombotic changes at
      the site of insertion or at the tip of the catheter, and in the other 14 cows the
      jugular vein was completely thrombosed, from 7 to 20 cm. Catheter-related damage
      to the intima, chemical damage by irritating medications and reduced host
      resistance attributable to the underlying illness were thought to be possible
      causes of the thrombophlebitis.

PMID- 8560701
TI  - Comparative pharmacodynamics of flunixin, ketoprofen and tolfenamic acid in
      calves.
AB  - The pharmacodynamics of the non-steroidal anti-inflammatory drugs flunixin,
      tolfenamic acid and ketoprofen were studied in calves after intravenous
      administration. An acute inflammatory reaction was induced in tissue cages by the
      intracaveal injection of the mild irritant carrageenan, and the inhibition of
      inflammatory mediators and enzymes was investigated. The substances measured in
      the exudate included the enzymes (active and total metalloproteases, serine and
      cysteine proteases, acid phosphatase [AP], lactate dehydrogenase [LDH] and beta
      glucuronidase) and the eicosanoids (prostaglandin [PG]E2 and leukotriene [LT]B4).
      Studies were also made of inhibition of the synthesis of serum thromboxane (Tx)B2
      ex vivo, of bradykinin-induced oedema in vivo and of the generation of superoxide
      anions (O2-) in vitro. None of the drugs affected the concentration of LTB4, or
      the activities of metalloproteases, cysteine and serine proteases, AP or LDH in
      the exudate. All the drugs inhibited the synthesis of serum TxB2 and exudate PGE2
      and inhibited the release of beta-glucuronidase. They also decreased the
      oedematous response to intradermally injected bradykinin and inhibited the
      generation of O2- ions by neutrophils in vitro. These actions may contribute to
      the anti-inflammatory effects of the drugs and hence to their clinical efficacy.

PMID- 8560703
TI  - In vitro antibiotic sensitivity of Ornithobacterium rhinotracheale strains from
      poultry and wild birds.

PMID- 8560704
TI  - Infertility associated with monosomy-X in a crossbred cattle heifer.

PMID- 8560705
TI  - Reduced fecundity and egg viability in the pasture tick (Ixodes ricinus) exposed
      to closantel.

PMID- 8560706
TI  - An outbreak of avian influenza in poultry in Pakistan.

PMID- 8560707
TI  - Multiple cases of maedi and visna in a flock in East Anglia.

PMID- 8560708
TI  - Mycoplasma canis in a British calf.

PMID- 8560709
TI  - Cold water vibriosis in Shetland salmon.

PMID- 8560710
TI  - Protests against live animal exports.

PMID- 8560711
TI  - Veterinary nursing examinations.

PMID- 8560712
TI  - Welfare of caged birds.

PMID- 8560713
TI  - A live attenuated vaccine for the control of avian coccidiosis: trials in broiler
      breeders and replacement layer flocks in the United Kingdom.
AB  - Losses caused by coccidiosis are a significant problem in the rearing of breeder
      and layer flocks. A live vaccine has been developed that contains attenuated
      lines of the seven species of Eimeria that infect the chicken. The attenuated
      lines were derived from virulent strains by selection for earlier development in
      chickens. In 11 field trials, the performance of vaccinated chicks was compared
      with that of matched controls receiving conventional drug prophylaxis. The
      vaccine was given in the drinking water to 116,600 young chickens and provided
      excellent control of coccidiosis. The occurrence of coccidial oocysts in the
      litter, coccidial lesions post mortem and overt coccidiosis was markedly lower in
      the vaccinated birds than in the controls.

PMID- 8560714
TI  - Persistence of the effect of a moxidectin pour-on against naturally acquired
      cattle nematodes.
AB  - In a controlled trial with 32 calves on the persistence of the effect of a 0.5
      mg/kg moxidectin pour-on against cattle nematodes the following periods of
      persistence were observed: Virtually 100 per cent efficacy for more than five
      weeks against Dictyocaulus viviparus (total numbers and juveniles) and Ostertagia
      species (total numbers, inhibited early fourth stage larvae [L4] and juveniles);
      over 97 per cent for more than four weeks against Trichostrongylus axei (total
      numbers, inhibited early third stage larvae [L3] and juveniles); 100 per cent for
      more than two weeks against T vitrinus (total numbers and inhibited early L3),
      and more than 90 per cent against Cooperia species (total numbers and inhibited
      early L4), and 89 per cent against L4 of Nematodirus species. Moxidectin thus had
      a more persistent effect against worms from the lungs and the abomasum than
      against worms from the small intestine, particularly because differences were
      observed between Trichostrongylus species from both locations. The population
      dynamics of T axei and T vitrinus in the calves appeared to differ from that in
      sheep. The relatively high percentages of inhibited early L3 in the untreated
      calves suggest that there was a much stronger tendency for a seasonal pattern of
      inhibition than in sheep.

PMID- 8560715
TI  - Idiopathic infective arthritis of the coxofemoral joint in a mature horse.
AB  - A mature thoroughbred-cross gelding developed chronic severe hindlimb lameness.
      Despite intensive clinical investigation, the diagnosis of infective arthritis of
      the coxofemoral joint was difficult, and a definitive diagnosis was reached only
      after synoviocentesis of the joint. The horse was euthanased and examined
      thoroughly post mortem but no definitive aetiology for the condition was
      discovered.

PMID- 8560716
TI  - Bilateral upward patellar fixation in two pregnant beef heifers.

PMID- 8560717
TI  - Clinical science, veterinary science and comparative medicine: problems of
      continuing neglect.

PMID- 8560718
TI  - Ryegrass staggers.

PMID- 8560719
TI  - BSE compensation.

PMID- 8560720
TI  - Docking of puppies' tails.

PMID- 8560721
TI  - Risk of parasitic gastroenteritis in sheep.

PMID- 8560722
TI  - Patterns of feeding and behaviour in horses recovering from dysautonomia (grass
      sickness).
AB  - Three horses suffering from grass sickness were treated successfully but showed
      clinical signs which varied in severity and duration. They were all characterised
      by marked and often erratic changes in behaviour and appetite.

PMID- 8560723
TI  - Pulmonary function changes induced by three regimens of bronchodilating agents in
      calves with acute respiratory distress syndrome.
AB  - Two aerosolised bronchodilators, one sympathomimetic and one parasympatholytic,
      were tested either alone or in combination for their ability to improve the
      pulmonary function of double-muscled calves suffering from acute respiratory
      distress syndrome. In control animals treated with 0.9 per cent saline the
      parameters of pulmonary function and signs of clinical distress did not change
      significantly within the hour following the first treatment. Among the other
      animals, both at one hour and seven days after the first treatment, the most
      clinical improvement was observed in the animals treated with both
      bronchodilators and the least in the animals treated with clenbuterol
      hydrochloride. One hour after the first treatment the respiratory system
      compliance of the animals treated with ipratropium bromide and the arterial
      oxygen tension of the animals treated with both bronchodilators were
      significantly enhanced. After seven days the resistive parameters, the rectal
      temperature and the respiratory rate were also significantly improved in the
      animals treated with ipratropium bromide or both bronchodilators whereas only the
      respiratory rate and rectal temperature were significantly reduced in the animals
      treated with clenbuterol hydrochloride.

PMID- 8560724
TI  - Activities of selected aerobic and anaerobic enzymes in the gluteus medius muscle
      of endurance horses with different performance records.
AB  - Biopsies of the gluteus medius muscle were taken at three different depths from
      36 endurance horses aged 8.42 +/- 2.85 years and of both sexes. Twenty of the
      horses were considered to be excellent performers on the basis of the mean speed
      of their three fastest records in endurance events over the previous two or three
      years, whereas 16 were moderate performers. The biopsy samples were analysed for
      the activities of the enzymes citrate synthase (an indicator of citric acid cycle
      activity), 3-OH-acyl-CoA-dehydrogenase (an indicator of lipid oxidation) and
      lactate dehydrogenase (an indicator of anaerobic metabolism). The 20 excellent
      performers had higher activities of citrate synthase (P < 0.001) and 3-OH-acyl
      CoA-dehydrogenase (P < 0.02) than the 16 moderate performers. The activities of
      citrate synthase and 3-OH-acyl-CoA-dehydrogenase increased by 65 per cent and 75
      per cent, respectively, and the activity of lactate dehydrogenase decreased by 23
      per cent in the samples taken at successively greater depths. There was a strong
      linear relationship between the ratios of the activities of lactate
      dehydrogenase/citrate synthase and lactate dehydrogenase/3-OH-acyl-CoA
      dehydrogenase and the depth from which the samples were taken for both
      performance groups (P < 0.001). The intercepts of the regression lines were
      higher in the moderate than in the excellent performers (P < 0.001 and P < 0.01
      for the two ratios), showing that the endurance horses with the better
      performance record had a greater aerobic capacity and a relatively lower
      anaerobic capacity in the gluteus medius muscle than the horses with a poorer
      record.

PMID- 8560725
TI  - Prevalence of leptospire infections in buffalo herds in Italy.

PMID- 8560726
TI  - Lead toxicosis in captive houbara bustards (Chlamydotis undulata maqueenii).

PMID- 8560727
TI  - Pasteurellosis in elk (Cervus elaphus): DNA fingerprinting of isolates.

PMID- 8560728
TI  - Reorganization of the State Veterinary Service.

PMID- 8560729
TI  - Detection of FeLV antigen.

PMID- 8560730
TI  - Early calving.

PMID- 8560731
TI  - Veterinary manpower and recruitment.

PMID- 8560732
TI  - Swine dysentery: more unknown than known.
AB  - Swine dysentery (SD) is an economically important disease. It is caused by the
      spirochete Serpulina hyodysenteriae. In order to minimize the economic damage of
      SD, several methods to control this disease are recommended. Whereas hygienic
      measures and use of antimicrobials are actually practised for prevention,
      detection and exclusion of carriers of S. hyodysenteriae and vaccination against
      the disease still needs further attention. The last two methods require reliable
      and sensitive diagnostic tests and understanding of the pathogenesis of and
      immune development against SD. At present the detection of all individual
      carriers of S. hyodysenteriae is not yet assured, since the tests for screening
      individual animals are not satisfactorily evaluated as far as sensitivity and/or
      specificity are concerned. Studies on the pathogenesis of SD have been performed
      to develop a vaccine. Besides hemolysin/cytotoxin production, no other virulence
      factors have been identified with certainty for S. hyodysenteriae. Recently
      however, further indications for a role of motility in the pathogenesis of SD
      have been obtained. In this manuscript we summarize the most relevant recent
      findings.

PMID- 8560733
TI  - A fluorometric beta-glucuronidase assay for analysis of bacterial growth in milk.
AB  - The growth of common mastitis-causing bacteria in milk was followed by a
      fluorometric technique based on the release of fluorescent 4-methylumbelliferone
      (4-MU) from 4-methylumbelliferyl-beta-D-glucuronide by the beta-glucuronidase of
      bacterial or milk origin. Three of four Escherichia coli strains, all four
      strains of Streptococcus uberis (4/4) and Streptococcus agalactiae (4/4) produced
      beta-glucuronidase. Four Staphylococcus aureus strains (4/4) and one E. coli
      strain, though unable to produce the enzyme, activated the milk beta
      glucuronidase most probably by lowering the pH of bacterial cultures in milk for
      optimum activity of the indigenous enzyme. The beta-glucuronidase of milk, Str.
      uberis and Str. agalactiae origin had similar optimum pH ranges (5.3-6.6) while
      E. coli beta-glucuronidase was more active at neutral or slightly alkaline pH
      (6.8-7.7). The increase of beta-glucuronidase activity in milk cultures of E.
      coli, Str. uberis, Str. agalactiae and S. aureus seemed to parallel the increase
      of colony forming units and were dependent on the inoculum size. The time to
      reach a predetermined enzyme threshold in E. coli-milk cultures showed excellent
      linear relationship with the inoculum size.

PMID- 8560734
TI  - Production and characterization of monoclonal antibodies against Actinobacillus
      pleuropneumoniae serotype 1.
AB  - Three monoclonal antibodies (mAbs) against Actinobacillus pleuropneumoniae
      serotype 1, designated 4.2 A11 B5, 5.1 G8 F10 and 1.5 C5 F4 (IgG3, IgG2b and IgM
      respectively), were produced and characterized. mAbs 4.2 A11 B5 and 5.1 G8 F10
      were directed against different epitopes located in the O chain of the LPS. Both
      clones also recognized reference strains of A. pleuropneumoniae serotypes 9 and
      11. The mAb 1.5 C5 F4 reacted with the reference strain of A. pleuropneumoniae
      serotype 1, with the encapsulated strain 4045 (but not with its non-capsulated
      mutant) and with A. pleuropneumoniae serotype 1 purified capsular polysaccharides
      (CPS). The epitope was sensitive to periodate oxidation, heat-labile, and located
      in the capsular material of A. pleuropneumoniae serotype 1, as demonstrated by
      immunoblotting. Treatment of the CPS with 5% ammonium hydroxide eliminated the
      reaction, which may indicate that the epitope recognized by 1.5 C5 F4 mAb is a O
      acetyl containing determinant. When different A. pleuropneumoniae field strains
      were tested, the percentage of strains recognized by the mAbs varied with the mAb
      and the test used. Cross-reactions associated with the LPS of some A.
      pleuropneumoniae serotype 5 field strains could be observed with the 4.2 A11 B5
      mAb. Of the three mAbs characterized, 1.5 C5 F4 seemed to be the most suitable
      for A. pleuropneumoniae serotype 1 detection since it reacted with 99% of
      serotype 1 field strains and it did not recognize any of the strains belonging to
      other serotypes.

PMID- 8560735
TI  - Association with HeLa cells by Rhodococcus equi with and without the virulence
      plasmid.
AB  - HeLa cell association was examined in eight Rhodococcus equi isolates containing
      80-85 kb plasmids and their plasmid negative derivatives, and in two other
      plasmid negative R. equi strains. Seven of the eight plasmid positive strains
      possessed an 85 kb plasmid and produced the virulence-associated protein (VapA)
      detected by monoclonal antibody staining in immunoblots; one of the eight had an
      80 kb plasmid but did not produce VapA. Curing of the plasmids by repetitive
      subcultures at 42 degrees C in broth was confirmed by colony and DNA dot blot
      hybridization with a 7.5 kb BamHI-HindIII plasmid fragment probe, by attempted
      isolation of plasmid DNA, and by demonstration of lack of VapA. Most strains
      associated well with HeLa cells and no relationship was found with plasmid status
      and possession of VapA. Association with HeLa cells was significantly greater for
      strains with a dry colony type than for those with a mucoid colony, a result
      which correlated with hydrophobicity of the colonies. HeLa cell association does
      not correlate with the presence of the virulence plasmid in R. equi.

PMID- 8560736
TI  - Bronchopneumonia in mice caused by Pasteurella haemolytica A2 after
      predisposition by ovine Bordetella parapertussis.
AB  - Initial intranasal inoculation of four to eight-week-old Swiss White mice with
      7.5 x 10(6) colony forming units (cfu) of ovine B. parapertussis followed 30 min,
      three or five days, by intranasal inoculation with 1.4 x 10(5) cfu of Pasteurella
      haemolytica A2 resulted in a more severe infection pattern than when either agent
      was administered alone. Histopathological examination showed that inoculation
      with B. parapertussis alone caused a bronchopneumonia the severity of which was
      dependant upon the infecting dose. Bacteria were recovered up to 10 days after
      inoculation. P. haemolytica alone had no apparant pathogenic effect and was
      cleared from the lungs within 24 h. When both agents were given in combination
      the lesions were most severe when P. haemolytica was administered three days
      after B. parapertussis infection. These findings suggest that B. parapertussis
      predisposes mice to subsequent infection with P. haemolytica and that the timing
      of the P. haemolytica administration influences the severity of the lung lesions.

PMID- 8560737
TI  - Stimulation of avian respiratory phagocytes by Pasteurella multocida: effects of
      the route of exposure, bacterial dosage and strain, and the age of chickens.
AB  - The effects of the route of exposure (intratracheal [IT], drinking water [DW] and
      aerosolization [AS]), the age of chickens, and the dose of two vaccine strains of
      Pasteurella multocida (CU and M-9) on the number, phagocytic proportion and
      capacity of macrophages, granulocytes and lymphocytes (collectively avian
      respiratory phagocytes [ARPs]) were analyzed. Administration of P. multocida via
      the DW even at very high dose failed to stimulate ARPs. In contrast,
      administration of both strains of P. multocida either IT or by AS resulted in
      rapid and highly significant increases in the numbers of ARPs. 10 x 10(9) colony
      forming units (cfu) of aerosolized P. multocidaCU strain activated ARPs maximally
      in both young (3-6 weeks of age) and old (4-6 months of age) chickens. Old
      chickens responded in dose dependent manner to 20 x 10(9), 8 x 10(9), and 4 x
      10(9) cfu of aerosolized P. multocida CU strain. Young chickens responded
      significantly only to 8 x 10(9) CU organisms. The M-9 and CU strains had limited
      differences in inducing migration of ARPs into the respiratory system of chickens
      or elevating phagocytic proportions and capacity of ARPs. The results indicate
      that the analyzed factors influence the response of ARPs to P. multocida to
      various degrees.

PMID- 8560738
TI  - Phenotypic characterization of Streptococcus dysgalactiae isolates from bovine
      mastitis by their binding to host derived proteins.
AB  - The binding of 80 Streptococcus dysgalactiae mastitis isolates from 51 farms to
      plasma and connective tissue proteins fibronectin (29 kDa N-terminal fragment),
      vitronectin, collagen type I, fibrinogen, alpha 2-macroglobulin, IgG, and albumin
      was studied. All isolates boiund the bovine 29 kDa fibronectin fragment and the
      binding of bovine fibrinogen, caprine albumin, bovine alpha 2-macroglobulin
      trypsin complexes and caprine IgG was also very frequent (92.5, 92.5, 72.5% and
      87.5%, respectively). Binding to human vitronectin was observed in 55% of the
      isolates, whereas only 20% of the isolates bound human type I collagen. None of
      the isolates bound native alpha 2-macroglobulin. Nearly all isolates (91%) bound
      more than 3 ligands. The bacterial binding sites for these proteins (termed here
      receptors) occurred in different combinations of which the combination
      fibronectin-, albumin-, fibrinogen-, vitronectin-, alpha 2-macroglobulin- and IgG
      receptor was the most common. More than one isolate was obtained from 10 farms.
      The isolates from 5 farms showed close similarity of binding profiles within the
      farm, indicating that they were of similar origin and suggesting that the binding
      characteristics were relatively stable. Wider variation among the isolates
      obtained from other 5 farms was detected. The different isolates of the same farm
      origin varied mostly in the binding of albumin, IgG and fibrinogen.
      Interestingly, a difference in the number of receptors between isolates from two
      different sampling areas was observed. The binding profiles offer a new
      phenotypic method for epidemiological studies and may also when combined with
      genetical studies provide more insight both into the role of the bacterial plasma
      and connective tissue protein receptors in the infection process and the
      regulation of receptor expression.

PMID- 8560739
TI  - Bactericidal activity of the bovine myeloperoxidase system against bacteria
      associated with mastitis.
AB  - Myeloperoxidase (MPO) is a lysosomal enzyme found in the primary granules of
      mammalian neutrophils. Together with MPO, peroxide and halide form a system of
      defense against bacteria. The present investigation was undertaken to study the
      bactericidal effects of the bovine-MPO/peroxide/halide system on pathogenic
      bacteria associated with bovine mastitis. We demonstrated that MPO together with
      oxidizing agents generated by xanthine oxidase, hypoxanthine and chloride form a
      potent antibacterial system against the common udder pathogens Staphylococcus
      aureus, Streptococcus uberis, Streptococcus agalactiae, Streptococcus
      dysgalactiae and Escherichia coli in a synthetic medium. However, when milk was
      added to the reaction mixture, the bactericidal properties of this enzyme system
      were completely inhibited. Loss of bactericidal activity in the milk-containing
      cultures was unable to be restored by increasing the concentration of MPO. Nor
      did an increase in concentrations of hypoxanthine and xanthine oxidase, or the
      replacement of the above-mentioned peroxidase generating system with a high
      concentration of hydrogen peroxide, significantly elevated the bactericidal
      activity that was inhibited by milk. The addition of bovine serum albumin to the
      synthetic medium reduced the bactericidal activity of the MPO/peroxide/chloride
      system in a dose-dependent manner. Therefore, milk proteins probably form adducts
      with strong bactericidal agents that are generated by the MPO system and thereby
      reduce the bactericidal potential of this system.

PMID- 8560740
TI  - Production and use of monoclonal antibodies to Microsporum canis.
AB  - Microsporum canis NCPF 179 and M. canis NCPF 177 dermatophyte cytoplasmic
      extracts (DCEs) were used as antigens to generate monoclonal antibodies (mAbs).
      Hybridomas with supernatants of optical density (OD) > 1 for homologous
      dermatophyte cytoplasmic extracts (CE) and OD < 0.5 for heterologous CE of
      Candida albicans tested by the enzyme-linked immunosorbent assays (ELISA) were
      selected for cloning. mAbs secreted by cloned hybridoma lines were screened
      against CE of M. canis, M. gypseum, M. equinum, M. distortum, Trichophyton
      verrucosum, C. albicans, Malassezia pachydermatis and Aspergillus fumigatus. The
      ELISA performed on clone supernatants identified a variety of different
      activities between the dermatophyte and other fungal CEs. The selected mAbs were
      used for immunoblotting of native and sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) gels. Immunoblots with some of the mAbs tested allowed
      the differentiation of strains belonging to different dermatophyte species and
      isolates belonging to the M. canis.

PMID- 8560741
TI  - Popliteal tendon transposition for stabilization of the cranial cruciate ligament
      deficient stifle joint in dogs: an experimental study.
AB  - Popliteal tendon transposition was performed in five dogs with surgically induced
      cranial cruciate ligament rupture. After a lateral approach to the stifle joint,
      the popliteal tendon was severed distal to the sesamoid bone and transposed
      cranially onto the tibial crest to mimic the sagittal orientation of the cranial
      cruciate ligament. The origin of the popliteal tendon on the lateral femoral
      condyle was preserved. Lameness was not clinically detectable 2 months after
      surgery. At 6 months postoperatively, there was minimal radiographic and
      histopathologic evidence of degenerative joint disease in the stifle joints that
      had underwent surgery. There was no gross or microscopic evidence of meniscal
      damage found at necropsy 6 months after surgery. Biomechanical studies are
      warranted before recommending the procedure.

PMID- 8560742
TI  - Distribution of topical agents in the frontal sinuses and nasal cavity of dogs:
      comparison between current protocols for treatment of nasal aspergillosis and a
      new noninvasive technique.
AB  - To document and compare patterns of distribution of topically applied antifungal
      medication, heads from 42 canine cadavers were assigned to seven treatment groups
      which included two current surgical treatment protocols for nasal aspergillosis,
      and a new, noninvasive method. Catheters (8 Fr) were placed through trephine
      holes into the frontal sinuses and nasal cavity. Dilute dye was injected through
      the catheters and the heads were sectioned sagittally. The administration of 5 mL
      of dye into the lateral frontal sinus and nasal cavity (group IA, 10 mL total)
      was compared with 25 mL injected through catheters placed bilaterally in the
      lateral frontal sinus and nasal cavity (group II, 100 mL total). Both were
      compared with the administration of 50 mL of dye through a catheter placed in the
      dorsal nasal meatus via each nostril (group III). The heads in group III had
      significantly (P < .05) better dye distribution to all cavities than group IA and
      better distribution to the rostral frontal sinus than group II. Groups IV to VI
      were designed to show the pattern of distribution of dye to the contralateral
      nasal cavity and frontal sinuses. In all groups, dye injected into the lateral
      frontal sinus did not cross into the ipsilateral rostral frontal sinus or vice
      versa unless the transverse septum dividing the compartments had been penetrated
      during trephination.

PMID- 8560743
TI  - Effects of growth factors and L-arginine on ischemic skin flaps in rats.
AB  - This study determined the effect of the polypeptide growth factors transforming
      growth factor-beta (TGF-beta), insulin-like growth factor-I (IGF-I), and growth
      hormone (GH) alone and in combination with dietary L-Arginine HCL (ARG) on skin
      flap survival in rats. Caudally based dorsal skin flaps were created in 110
      Sprague-Dawley rats. The rats were randomly assigned into three treatment groups,
      based on drinking water supplementation. Group 1 (n = 50) received ARG in their
      drinking water, group 2 (n = 50) received tap water alone, and group 3 (n = 10)
      received N-omega-nitro-L-arginine (L-NA) and hydralazine. Groups 1 and 2 were
      divided into subgroups of 10 rats each based on treatment with either: TGF-beta,
      IGF-I, GH, or IGF-I + GH. All subgroups that received GH had significantly
      greater (P < .0001) median body weight gains when compared with subgroups not
      receiving GH. L-arginine HCL when added to IGF-I negated the positive effects of
      IGF-I on both flap survival and weight gain. Although the rats in all subgroups
      from groups 1 and 2 had an increase in mean percent skin flap survival when
      compared with the water alone subgroup, only rats receiving IGF-I, or the
      combination of ARG with either TGF-beta or GH, had statistically significant
      enhanced skin flap survival. Rats in group 3 did not show an increase in skin
      flap survival when compared with the control subgroup.

PMID- 8560744
TI  - Ventral abdominal approach for laparoscopic ovariectomy in horses.
AB  - Eleven mares and four mules were ovariectomized by a ventral abdominal
      laparoscopic technique. This approach required tilting the operative table about
      30 degrees elevating the pelvis to allow observation of the ovaries. A
      triangulation technique with a single laparoscopic portal and four instrument
      portals was used. The ovarian pedicles were ligated and the ovaries were removed
      through a single enlarged instrument portal. Females ranged in age from 5 months
      to 18 years. Mean operative time was 44 minutes (range 20 to 90 minutes); mean
      operative time of the last seven animals was 26 minutes. Signs of abdominal pain
      occurred in three mules and one mare in the immediate postoperative period.
      Peritoneal fluid collected from six animals 48 hours after surgery had a mean
      leukocyte count of 34,463/microL: (range, 21,000 to 62,800/microL), mean protein
      concentration of 3.1 g/dL (range, 2.2 to 4.6 g/dL), and mean differential
      leukocyte count of 74% neutrophils and 26% mononuclear cells. The animals were
      confined for 2 weeks after surgery. Signs of estrus were observed in two mares
      within 6 months after ovariectomy. All owners reported satisfaction with the
      results of laparoscopic ovariectomy. The ventral abdominal laparoscopic approach
      permitted efficient and safe ovariectomy of foals and adults.

PMID- 8560745
TI  - Tube cystostomy for treatment of obstructive urolithiasis in small ruminants.
AB  - Tube cystostomy was used to treat 13 goats and two sheep with obstructive
      urolithiasis. The cystostomy tube was intermittently occluded 3 to 4 days after
      placement to determine if urine could be voided through the urethra. If the
      animal showed no discomfort during urination after the cystostomy tube had been
      occluded for several days, the tube was removed. This procedure was successful in
      relieving urethral obstruction in 12 animals. The mean time until the animal
      could urinate freely and until the cystostomy tube was removed was 11.5 and 14.4
      days respectively. Follow-up was available for 10 animals; seven were alive with
      no recurrence of urinary obstruction. One goat died from unrelated to urinary
      obstruction 1 year postoperatively. One goat died from unknown causes, and one
      goat died after urinary obstruction recurred.

PMID- 8560746
TI  - Complications of celiotomy incisions in horses.
AB  - Complications of celiotomy incisions were evaluated retrospectively in 274 horses
      that survived at least 1 month after surgery, or died or were euthanatized within
      1 month of surgery, as a direct result of these complications. Horses were
      divided into four groups; group A, a ventral median celiotomy for intestinal
      disease; group B, ventral median celiotomy for nonintestinal disease; group C,
      repair of an umbilical hernia; and group D, celiotomy in a region other than the
      midline. Specific incisional complications were peri-incisional edema, drainage,
      incisional abscess, suture sinus, and dehiscence. Incision-related complications
      occurred in 30% of the horses (group A, 40%; group B 18%; group C, 7%; and group
      D, 88%). Complications occurred more frequently in group D than group A (P =
      .009), which were higher than in groups B and C (P < .00001). Incisional hernia
      occurred in 28 of 256 (11%) horses that survived at least 4 months and were
      available for follow-up. Hernia formation was more common P < .00001) in horses
      that had other incisional complications (23 horses) than those without (5
      horses). Serous or purulent incisional drainage, were more likely to be
      associated with hernia formation than was serosanguineous drainage or other
      incisional complications.

PMID- 8560748
TI  - Confidential enquiry into perioperative equine fatalities (CEPEF)

PMID- 8560747
TI  - Jejunal intussusception: a complication of functional end-to-end stapled
      anastomoses in two ponies.
AB  - Jejunojejunal intussusception occurred after jejunal resection and stapled
      functional end-to-end anastomosis in two pony mares. In both mares, the lead
      point of the intussusception was the stapled functional end-to-end (FEE)
      anastomosis. The stapled free ends of jejunum were oversewn with an inverting
      suture pattern. A possible explanation for development of the intussusception was
      the acute angle created in the intestine by the FEE anastomosis. This angulation
      may have impaired flow of ingesta causing motility changes that predisposed the
      site to intussusception. Because the oversewn blind intestinal ends acted as the
      lead point for formation of the intussusception, it may be inadvisable to oversew
      the stapled anastomotic ends.

PMID- 8560749
TI  - Comparison of intra-articular and epidural morphine for analgesia following
      stifle arthrotomy in dogs.
AB  - We prospectively studied 18 dogs that presented for exploratory stifle
      arthrotomy, with or without meniscectomy, and lateral extracapsular stabilization
      as a result of cranial cruciate ligament rupture. Dogs were premedicated with
      acepromazine, induced with thiopental, and maintained with halothane in oxygen.
      Preoperatively, dogs were assigned to one of three groups. Group 1 (n = 6)
      received intra-articular morphine (0.1 mg/kg diluted in 1 mL/10 kg body weight of
      saline) and epidural saline (1 mL/5 kg body weight saline plus the volume of
      saline representing 0.1 mg/kg of morphine). Group 2 (n = 6) received intra
      articular saline (1 mL/10 kg body weight of saline plus the volume of saline
      representing 0.1 mg/kg of morphine) and epidural saline (1 mL/5 kg body weight
      saline plus the volume of saline representing 0.1 mg/kg of morphine). Group 3 (n
      = 6) received intra-articular saline (1 mL/10 kg body weight of saline plus the
      volume of saline representing 0.1 mg/kg of morphine) and epidural morphine (0.1
      mg/kg of morphine diluted in 1 mL/5 kg body weight saline). The efficacy of each
      analgesia regimen was evaluated for 6 hours postoperatively with a pain score
      based on subjective and objective variables. Serum cortisol and blood glucose
      concentrations were measured. Butorphanol was used to provide analgesia as needed
      based on a predetermined maximum pain score. Supplemental analgesics were
      required postoperatively every 2 to 3 hours for 6 hours in all dogs that did not
      initially receive analgesics (group 2). Pain scores were significantly lower in
      dogs administered morphine intra-articularly (group 1) and epidurally (group 3)
      at 30 minutes and 30, 120, and 360 minutes, respectively, compared with dogs that
      did not initially receive analgesics (group 2). One dog in group 1 and one dog in
      group 3 required supplemental analgesia with butorphanol. There was no difference
      between analgesia produced by intra-articular morphine compared with that of
      epidural morphine. Side effects after intra-articular or epidural morphine were
      not observed. Intra-articular administration of morphine can produce effective
      analgesia in dogs comparable with that produced by epidural administration of
      morphine.

PMID- 8560750
TI  - The effects of atropine and glycopyrrolate on heart rates in conscious mature
      goats.
AB  - The effects of intravenously administered atropine (0.2 mg/kg) and glycopyrrolate
      (0.01 mg/kg) on heart rate were studied in 10 conscious mature goats. In a drug
      cross-over fashion, either atropine, glycopyrrolate, or 0.9% saline solution was
      administered using the same volume (0.05 mL/kg). Atropine and glycopyrrolate
      caused a significant increase in heart rate (P < .05), whereas saline solution
      (0.09%) did not. The mean percent changes in heart rate from baseline were
      similar for atropine and glycopyrrolate up to 14 minutes after administration.
      Thereafter, glycopyrrolate had a significantly greater mean change in heart rate
      than atropine, ie, up to 29 minutes (P < .05). Within the atropine group, the
      mean percentage changes in heart rate became significantly lower compared with
      the initial increase (1 minute) starting at 11 minutes. For the glycopyrrolate
      group, the mean percent changes became significantly lower starting at 27
      minutes. Glycopyrrolate and atropine had a mean percentage change in heart rate
      of greater than 1.0%, up to 31 and 22 minutes, respectively. At the doses used,
      glycopyrrolate had longer duration of action than atropine but the magnitude of
      increase was similar.

PMID- 8560751
TI  - The activity of lecithin:cholesterol acyltransferase in the serum of cows at
      parturition or with fatty liver.
AB  - The activity of lecithin:cholesterol acyltransferase (LCAT), which is responsible
      for esterification of plasma cholesterol, was evaluated in bovine serum. It was
      associated with the high-density lipoprotein fraction that contains
      apolipoprotein A-I, an activator of LCAT. In lactating cows, the activity was
      around 1000 U (decrease in nmol of free cholesterol per h per ml of serum),
      slightly higher than in 1-month-old calves. LCAT activity decreased around
      parturition, at which the time the serum concentrations of cholesteryl esters and
      free cholesterol were concomitantly decreased. A reduced LCAT activity was also
      found in cows with fatty livers induced by the administration of ethionine. In
      the cows with fatty livers, the serum concentration of cholesteryl esters was
      markedly decreased, whereas that of free cholesterol was only slightly decreased,
      thereby increasing the free- to esterified-cholesterol ratio. These results
      suggest that the decrease in LCAT activity may be involved in the reduction in
      fertility associated with fatty liver because esterification of cholesterol by
      LCAT is essential for its transport from the liver to peripheral tissues, such as
      the corpus luteum, and because cholesterol serves as the source of progesterone
      synthesis in the latter organ.

PMID- 8560752
TI  - Determination of a reference range for fructosamine in feline serum samples.
AB  - Fructosamine, the product of a non-enzymatic reaction between glucose and serum
      proteins, is a component of serum which reflects long-term deviations from normal
      glucose and protein homeostasis. Thirty-one healthy, intact, domestic short
      haired cats, living under uniform feeding and environmental conditions, were
      sampled to calculate a reference range for feline serum fructosamine. The results
      were obtained using a nitroblue tetrazolium colorimetric method. The analytical
      assay was evaluated by calculation of within-run and between-day variation,
      detection limit, and accuracy. Serum fructosamine concentrations were
      approximately normally distributed and the calculated reference range was 146-271
      mumol/L (mean 209 mumol/L, standard deviation 31.6 mumol/L). There were no
      significant differences between male and female cats, or between cats older and
      younger than 12 months. Previously conducted studies give higher reference
      ranges, possibly because of differences in the test procedure and homogeneity of
      the test population.

PMID- 8560753
TI  - A lectin histochemical study of the zygomatic salivary gland of adult dogs.
AB  - Seven lectins (PNA, DBA, SBA, UEA I, LTA, WGA and ConA), conjugated with
      horseradish peroxidase, were used to characterize the glycosidic residues in the
      zygomatic gland of adult dogs. In some cases (PNA and DBA), lectin staining was
      preceded by neuraminidase digestion. The acinar and tubular cells produced
      glycoconjugates with different sugar residues, presenting binding sits for all of
      the lectins used. The apical surfaces of the cells lining the intra- and
      interlobular ducts were also stained by all the lectins. In contrast, the
      demilunar cells only reacted with the Neu-PNA sequence and Con A.

PMID- 8560755
TI  - Clinical disorders observed in anteaters (Myrmecophagidae, Edentata) in
      captivity.
AB  - The major health problems found in 103 captive lesser anteaters (Tamandua
      tetradactyla) and giant anteaters (Myrmecophaga tridactyla), family
      Myrmecophagidae, are presented and correlated with management. The most common of
      200 recorded clinical disorders involved the digestive system (26%), nutritional
      deficiency (20%), injury (15.5%), respiratory system (10%), skin (7%) and
      circulatory system (4.5%), but 13% of the cases were inconclusive. Parasites were
      identified in 48.5% of faecal samples, mainly the eggs of nematodes (40%), of
      which the commonest were Trichuris spp (28%) and Strongyloides spp (11%);
      protozoa (16%), of which the commonest were Eimeria spp (10%), Entamoeba spp (5%)
      and Giardia spp (1%); and cestodes (8%) and acanthocephalids (1%). Bacteria
      cultured from the various materials included Salmonella enteritidis, S.
      cholerasuis, Escherichia coli, Enterobacter aerogenes, Streptococcus spp and
      Staphylococcus spp. The ectoparasites found were Amblyomma spp and Otodectis spp
      (Arthropoda, Acaridae).

PMID- 8560756
TI  - A caprine experimental model for studies on inflammation.
AB  - A new experimental model for in vivo studies on local inflammation in the goat is
      presented. The teat and udder cisterns were separated by a surgical procedure,
      resulting in the teat cistern being an isolated pouch which is easily accessible
      through the teat canal and suitable for experimental studies. The surgery was
      consistently successful in closing the passage and no post-surgical complications
      were observed. The model was applied to a study of the inflammatory response
      induced by infusion of Salmonella endotoxin. A marked response was observed as
      measured by the accumulation of leukocytes, serum albumin and N-acetyl-beta-D
      glucosaminidase (NAGase) in the test cistern. An initial increase in serum
      albumin, indicating an increase in the epithelial permeability, was observed from
      1.5 h after endotoxin infusion. Approximately 0.5 h later, the cell count started
      to increase, reaching its peak level 3 h after infusion. The NAGase concentration
      was closely correlated with the cell count. The model provides new possibilities
      for in vivo studies on local inflammation and fulfils many of the requirements of
      an inflammatory model; for example, it allows non-traumatic repeated samplings
      from the same animal. The goat is a suitable experimental animal for many studies
      and, as each goat has two teats, intra-goat comparisons can be performed.

PMID- 8560757
TI  - Some pharmacokinetic parameters of doxycycline in east African goats after
      intramuscular administration of a long-acting formulation.
AB  - A compartmental and non-compartmental study was carried out on five adult goats
      following intramuscular administration of doxycycline at 20 mg/kg bodyweight. The
      concentration of the drug in serum was determined by a microbiological assay
      employing Bacillus cereus var mycoides (ATCC 11778) as the test organism. The
      mean serum concentration (Cmax) and the time of maximum concentration (Tmax) were
      1.87 micrograms/ml and 0.85 h, respectively. Using compartmental analysis, the
      plasma concentration-time curve of doxycycline best fitted a three-compartment
      open model with first-order absorption. A three-phase disposition of doxycycline
      was found, the terminal elimination half-life being approximately 40 h. The
      statistical moment theory was mainly used for non-compartmental analysis. The
      value obtained for the mean residence time (MRT) was 16.4 h. The mean values for
      the volume of distribution at steady state (Vdss), determined by compartmental
      and non-compartmental analyses, were 8.73 and 13.19 L/kg, respectively. There
      were no statistically significant differences when the major pharmacokinetic
      parameters were compared. It was concluded that the pharmacokinetic behaviour of
      doxycycline in goats after intramuscular administration is characterized by a
      three-compartment model with a slow terminal elimination phase. Based on current
      knowledge, this could be due to enterohepatic recycling and/or flip-flop
      kinetics. The study indicated that a single intramuscular administration of 20
      mg/kg of doxycycline may only provide therapeutic concentrations for up to 24 h
      owing to slow absorption at the injection site.

PMID- 8560758
TI  - Exogenous mouse mammary tumor virus (MMTV) infection induces endogenous MMTV sag
      expression.
AB  - The mouse mammary tumor virus (MMTV) superantigen (Sag) protein is involved in
      the transmission of milk-borne MMTV from virus-infected milk in the gut to the
      target mammary gland tissue. Using an RT-PCR assay for in vivo MMTV infection,
      BALB/c or C3H mice nursed on C3H MMTV-infected mothers showed sag mRNA expression
      in intestine, spleen, and thymus as early as 1 day after infection, whereas
      uninfected BALB/c control animals had approximately 10- to 30-fold lower sag
      expression. Further fractionation experiments with small intestine indicated that
      sag expression occurred in gut-associated lymphoid cells. Restriction enzyme
      digestion of PCR products indicated that the sag mRNA detected was derived from
      the endogenous MMTVs, and sequencing analysis confirmed that the PCR products
      were derived from endogenous MTv-6. Expression of C3H-specific mRNA was
      detectable in BALB/cfC3H or C3H tissues by RNase protection or by RT-PCR.
      Endogenous MMTV sag expression was low in spleen and undetectable in thymocytes
      of C3H MMTV-infected C57BL/6 mice, a strain resistant to C3H MMTV tumorigenesis
      and defective for MHC class II I-E molecules. The RT-PCR assay for sag mRNA
      appears to measure the Sag-induced stimulation previously predicted for milk
      borne MMTV infection. Together these data suggest that exogenous MMTV sag
      expression is minimal, but sufficient to rapidly stimulate transcription of
      endogenous MMTV sag mRNA in B- and T-cells in an MHC class II I-E-dependent
      manner. The endogenous sag expression on maternal lymphocytes may increase the
      number of proliferating T-cells available for milk-borne MMTV infection.

PMID- 8560754
TI  - Applications of DNA amplification techniques in veterinary diagnostics.
AB  - An overview of the principles of the polymerase chain reaction, ligase chain
      reaction, self-sustained sequence replication and Q beta replicase is given. The
      application of these methods for the diagnosis of veterinary infectious and
      hereditary diseases as well as for other diagnostic purposes is discussed and
      comprehensive tables of reported assays are provided. Specific areas where these
      DNA-based amplification methods provide substantial advantages over traditional
      approaches are also highlighted. With regard to PCR-based assays for the
      detection of viral pathogens, this article is an update of a previous review by
      Belak and Ballagi-Pordany (1993).

PMID- 8560759
TI  - N-linked glycans in the CD4-binding domain of human immunodeficiency virus type 1
      envelope glycoprotein gp160 are essential for the in vivo priming of T cells
      recognizing an epitope located in their vicinity.
AB  - Deglycosylation of viral glycoproteins has been suggested to influence the number
      of available T cell determinants and to increase T cell recognition of antigens.
      In this study, we have investigated whether T cell responses to the HIV-1
      envelope glycoprotein gp160 were influenced by deletion of three N-glycans of the
      protein. Wild type (wt) and a mutated form of gp160 (gp160A123) lacking the three
      N-glycans in the C-terminal CD4-binding region efficiently induced antigen
      specific T cell responses in mice of the H-2b, H-2d, and H-2k haplotypes.
      Further, T cells primed by either wt gp160 or gp160A123 were stimulated in vitro
      to a similar extent by the homologous and heterologous protein, indicating that
      deletion of the glycans did not affect the overall immunogenicity and
      antigenicity of gp160A123. Wild-type gp160 and gp160A123 induced comparable T
      cell responses to those of epitopes which with respect to the secondary structure
      of gp160 were distant from the deleted glycans. However, in mice of the H-2b
      haplotype, wt gp160 primed T cells which responded in vitro to a peptide
      containing one of the deleted N-glycosylation sites (Asn448), whereas T cells
      induced by gp160A123 were unable to recognize this peptide. Thus, deletion of the
      glycans abrogated the in vivo priming of T cells recognizing an epitope in close
      proximity to the deletion sites. Furthermore, enzymatically deglycosylated gp160
      failed to induce a T cell response to this epitope. These results indicate that
      the in vivo generation of certain T cell determinants from glycoproteins is
      dependent on the glycosylation of the protein.

PMID- 8560760
TI  - The capsid architecture of channel catfish virus, an evolutionarily distant
      herpesvirus, is largely conserved in the absence of discernible sequence homology
      with herpes simplex virus.
AB  - Although herpesviruses have a wide host range and their genomes vary
      substantially in size, the nucleocapsid appears to be a conservative element of
      viral design. The capsid shell is icosahedrally symmetric (T = 16), and 125 nm in
      diameter and 15nm thick in the case of herpes simplex virus 1 (HSV-1). Channel
      catfish virus (CCV) has the gross morphology of a herpesvirus, although no
      relationship to other herpesviruses is evident from the sequences of its
      proteins. To examine CCV capsid architecture more closely, we have determined its
      structure by cryoelectron microscopy and three-dimensional image reconstruction.
      The CCV capsid is smaller than that of HSV-1, but its 12% smaller genome is
      packed to essentially the same average density; its icosahedral facets are
      flatter, and its shell is about 20% thinner, consistent with the smaller size of
      its major capsid protein. Otherwise, their major features are remarkably similar:
      CCV has the same triangulation number; its hexons and pentons also have chimney
      like protrusions with an axial channel through each capsomer; and there are
      "triplexes" on the outer surface at the sites of local threefold symmetry. The
      basic herpesvirus capsid architecture is, therefore, remarkably well conserved in
      CCV and implies a utilitarian basis to this design. The protein composition of
      CCV mirrors that of HSV-1, except for the absence of the 12-kDa protein, VP26,
      which is dispensable for assembly in the HSV-1 system and, apparently, wholly
      dispensable for CCV.

PMID- 8560761
TI  - Effects of subtle changes in the SU protein of ecotropic murine leukemia virus on
      its brain capillary endothelial cell tropism and interference properties.
AB  - PVC-211 murine leukemia virus (MuLV) is a neuropathogenic variant of Friend MuLV
      (F-MuLV) that causes a rapidly progressive neurodegenerative disease in
      susceptible rodents. PVC-211 MuLV, but not the parental F-MuLV, can infect rat
      brain capillary endothelial cells (BCEC) efficiently, and the major determinant
      for BCEC tropism of PVC-211 MuLV is localized within the XbaI-BamHI fragment of
      the viral genome containing the 5' half of the env gene. To further dissect the
      XbaI-BamHI region for its effects on BCEC tropism, we constructed recombinant
      viruses between PVC-211 MuLV and F-MuLV and tested their infectivity on a cell
      line established from rat BCEC. Our results indicated that Glu116-to-Gly and
      Glu129-to-Lys substitutions in the background of the F-MuLV envelope SU protein
      were sufficient for conferring BCEC tropism on the virus. Interference studies of
      these viruses on Rat-1 fibroblastic cells showed that the structure of the SU
      protein encoded by the XbaI-BamHI region also has significant effects on their
      affinity for the rat ecotropic MuLV receptor. These results support the
      possibility that structural elements I and II of the SU protein are important
      determinants for virus-receptor interaction.

PMID- 8560762
TI  - The product of a 1.9-kb mRNA which overlaps the HSV-1 alkaline nuclease gene
      (UL12) cannot relieve the growth defects of a null mutant.
AB  - Alkaline nuclease, a relatively abundant viral phosphoprotein in herpes simplex
      virus type 1 (HSV-1)- or HSV-2-infected cells, is encoded by a 2.3-kb mRNA (R. H.
      Costa, K. G. Draper, L. Banks, K. L. Powell, G. Cohen, R. Eisenberg, and E. K.
      Wagner, 1983. J. Virol. 48, 591-603). This mRNA is a member of a family of five
      unspliced 3'-coterminal messages. Costa et al. proposed that another member of
      this family of mRNAs (1.9-kb) may encode an N-terminally truncated protein which
      shares its carboxy-terminus with the alkaline nuclease protein. We previously
      described the isolation of AN-1, a deletion/insertion mutant of the alkaline
      nuclease gene (S. K. Weller, R. M. Seghatoleslami, L. Shao, D. Rowse, and E. P.
      Carmichael, 1990. J. Gen. Virol. 71, 2941-2952). The deletion in AN-1 would be
      predicted to abolish gene products of both the 2.3- and the 1.9-kb mRNAs. To
      investigate whether the putative truncated version of alkaline nuclease encoded
      by the 1.9-kb mRNA has enzymatic activity and plays a role in the viral life
      cycle, a viral mutant (AN-F1) was constructed which is predicted to abolish the
      gene product of the 2.3-kb mRNA (full-length alkaline nuclease) but leave intact
      the putative product of the 1.9-kb mRNA. Using a highly sensitive polyclonal
      antiserum raised against a bacterially expressed full-length alkaline nuclease,
      we observed a 60-kDa protein in KOS- and AN-F1-infected cells but not in AN-1
      infected cells. This suggests that the 60-kDa protein is likely to be expressed
      from the 1.9-kb mRNA; the open reading frame is now designated UL12.5. Despite
      the presence of the 60-kDa band, AN-F1 failed to exhibit any alkaline exonuclease
      activity. This result suggests that the truncated polypeptide (UL12.5) is not
      enzymatically active, has low levels of activity, or possesses enzymatic activity
      which is not detected because of the low abundance of the polypeptide. AN-1 and
      AN-F1 are both severely restricted with respect to growth in Vero cells, as viral
      yields are 100- to 1000-fold lower than those of wild-type virus. We previously
      reported that the major defect in AN-1 is in the ability of DNA-containing
      capsids which form in the nucleus to mature into the cytoplasm (L. Shao, L. M.
      Rapp, and S. K. Weller, 1993. Virology 196, 146-162); AN-F1 exhibits the same
      defect. These results indicate that although the 1.9-kb mRNA encodes a 60-kDa
      protein presumably from the UL12.5 open reading frame, this polypeptide cannot
      substitute for the full-length UL12 product.

PMID- 8560763
TI  - Subgroup B adenovirus type 35 early region 3 mRNAs differ from those of the
      subgroup C adenoviruses.
AB  - Adenovirus type 35 (Ad35) is a member of Ad subgroup B, DNA homology cluster B2.
      The B2 Ads are unique in that they are isolated most frequently from
      immunosuppressed individuals such as AIDS patients and bone marrow transplant
      recipients and in that they have a tropism for the urinary tract. One region of
      the Ad genome which may influence serotype specific pathology is early region 3
      (E3). E3 of subgroup C Ad2 and Ad5 has been shown to encode proteins which
      counteract the immune response to Ad infection. While a great deal is known about
      gene expression of the subgroup C Ad E3s, little is known about the E3 gene
      expression from the subgroup B Ads. Although some E3 open reading frames (ORFs)
      are shared between subgroups B and C, there are additional ORFs that appear in
      subgroup B. This paper demonstrates the results of an analysis of gene expression
      from the Ad35 E3 and describes differences in splicing and polyadenylation
      between the Ad35 and Ad2 E3s. RT-PCR, cDNA sequencing, RNase protection, 3'RACE,
      and Northern blotting techniques were utilized to identify, quantify, and
      determine the structure of six Ad35 E3 mRNAs predicted to encode at least seven
      proteins. A common intron that is removed during splicing of the subgroup C E3
      mRNAs is not removed from Ad35 E3 mRNAs, and only one E3 polyadenylation signal
      is present in the Ad35 E3 while two polyadenylation signals are used in the
      formation only one E3 polyadenylation signal is present in the Ad35 E3 while two
      polyadenylation signals are used in the formation of subgroup C E3 mRNAs. The
      quantity of individual mRNAs encoding homologous proteins for Ad35 and Ad2 also
      differ substantially, presumably because of the absence in Ad35 of cis-acting
      signals which have been shown to be important for regulation of Ad2 E3 pre-mRNA
      processing. Such information should contribute to an understanding of the role
      the E3 plays in determining subgroup B Ad pathogenesis in general and Ad35
      pathogenesis in particular.

PMID- 8560764
TI  - Human JC virus cAMP response elements functional for enhanced glial cell
      expression in differentiating embryonal carcinoma cells.
AB  - Human JC virus (JCV) is glial cell-specific for growth and expression. This
      specificity is attributed to the cis-acting sequences of the two 98-bp tandem
      repeats in the JCV regulatory region. JCV causes brain lesions, especially in
      AIDS patients. To study the expression of JCV in glial cells, the role of both
      repeat region TGAGCTCA sequences, which are homologous to the classical TGAGCTCA
      cAMP response element (CRE), was examined. The effect of the CRE on expression of
      the JCV early promoter (JCVE) in response to cAMP was studied with
      undifferentiated, glial and muscle P19 embryonal carcinoma cells. The results
      showed a threefold increase in response to cAMP only in the glial cells in which
      JCV is efficiently expressed. The direct in vivo role of the JCV CRE was
      confirmed by site-directed mutagenesis. Additionally, a CRE oligonucleotide was
      induced by cAMP in vivo, and in in vitro transcription assays with glial cell
      extracts. The early promoter of human BK virus containing nonhomologous CRE
      sequences was previously shown not to be glial cell-specific and failed to
      respond to cAMP in glial P19 cells in this study. Mobility shift assays showed
      the cAMP-induced in vitro interaction of glial cell protein(s) with the CRE
      oligonucleotide. Southwestern blot and uv crosslinking experiments identified an
      approximately 43-kDa protein interacting with the JCV CRE oligonucleotide. The
      results indicate that the in vivo expression of JCVE is specifically increased in
      response to cAMP only in glial cells and JCV CRE in vitro protein complexes are
      only detected in response to cAMP for glial cell extracts.

PMID- 8560765
TI  - Evolution of canine parvovirus involved loss and gain of feline host range.
AB  - Canine parvovirus (CPV) type-2 emerged as a new virus infecting dogs in 1978, and
      it was probably derived as a variant of feline panleukopenia virus or of a
      closely related virus infecting another carnivore. CPV type-2 was subsequently
      replaced in nature by antigenically variant viruses (CPV type-2a and CPV type-2b)
      which now coexist in dog populations worldwide. We show that CPV type-2 isolates
      did not replicate in cats, but that both CPV type-2a and CPV type-2b isolates
      replicated efficiently. About 10% of the viruses isolated from cats with natural
      parvovirus disease were antigenically indistinguishable from CPV type-2a or type
      2b. The capsid protein gene sequence of a 1990 feline parvovirus isolate ("FPV
      24") was essentially identical to the sequence of CPV type-2b viruses from dogs.
      The loss and reacquisition of the feline host range in CPV was most likely due in
      each case to small numbers of changes in a region of the virus capsid where three
      protein monomers interact.

PMID- 8560766
TI  - Sequence analysis of the E3 region and fiber gene of human adenovirus genome type
      7h.
AB  - Adenovirus type 7h is currently the predominant virulent genome type of serotype
      7 isolated in Argentina, Chile, and Uruguay in association with severe infantile
      pneumonia. In order to characterize possible molecular determinants of
      pathogenicity, the nucleotide sequence of a 5904-bp fragment (76 to 93 mu)
      containing the entire E3 region and the fiber gene of Ad7h was established. The
      organization of the ORFs within the E3 region was similar to that reported for
      the prototype strains of Ad7 and Ad3. A comparison of the nucleotide and amino
      acid sequences of all ORFs revealed a higher homology between Ad7h and Ad7p than
      between Ad7h and Ad3 for 12.0K and 16.1K, whereas the 15.3K ORF and the adjacent
      fiber gene were strikingly more homologous to those of Ad3 (99.5 vs 81.1% and
      98.2 vs 66.6%, respectively). The equivalent to ORF 7.7K in Ad7p was missing in
      Ad7h due to a deletion and a mutation affecting the start codon (ATG-->ATT).
      Although the hemagglutinin of the Ad7h fiber could not be characterized due to
      its lack of activity on monkey erythrocytes, our results indicate that Ad7h is an
      intermediate strain 7-3.

PMID- 8560767
TI  - Coexpression of a nonsyncytium inducer HIV-1 glycoprotein inhibits syncytium
      formation by another HIV-1 Env protein.
AB  - The biosynthesis and biological properties of the envelope glycoprotein from a
      primary isolate of the human immunodeficiency virus type 1, HIV-1 YU2, and the
      Env product from the laboratory-adapted strain, HIV-1 LAI were compared in the
      absence of viral replication. We found that the level of expression and
      proteolytic processing into gp120/gp41 complexes of both glycoproteins was
      equivalent and independent of the cell type used. Although the two glycoproteins
      were detected on the surface of HeLa cells expressing high levels of CD4, only
      the HIV LAI Env product induced significant syncytium formation. Interestingly,
      when both glycoproteins were coexpressed in HeLa-CD4 cells, syncytium formation
      was greatly reduced. However, cell fusion could be restored by increasing amounts
      of the LAI envelope gene product. HeLa-CD4 cells expressing either glycoprotein
      fused with high efficiency to CEM-A cells, a hybrid of CEM and peripheral blood
      mononuclear cells, indicating that both glycoproteins were expressed in a
      biologically active form on the surface of these cells. These studies suggest
      that primary isolates and laboratory adapted stains may require, in addition to
      the CD4 receptor, independent accessory membrane components for the fusion
      activation step. Our results agree with the concept that virus entry requires the
      concerted activation of each glycoprotein subunit of the Env oligomeric complex.

PMID- 8560768
TI  - Long-term cultivation and productive infection of primary thymocyte cultures by a
      thymocytopathic murine retrovirus.
AB  - ts1, a mutant of MoMuLV, selectively kills T cells and neurons in the infected
      host resulting in neuroimmunodegeneration. In the infected thymus there is an
      early increase in mitosis of thymocytes followed by rapid death, suggesting that
      thymocyte death may be induced by viral mitogenic activation. Studies on
      thymocytes obtained from ts1-infected mice indicated that the ts1-induced
      depletion of thymocytes is mediated through activation-induced death by
      apoptosis. To further investigate the interaction between ts1 and thymocytes, we
      have established long-term primary murine thymocyte cultures by placing the
      thymocytes together with thymic remnants in culture medium containing IL-2 and IL
      7. These thymocytes retained their immature phenotype and we susceptible to
      infection by ts1 and its parental wild-type MoMuLV. ts1-infected thymocytes
      proliferated initially at accelerated rate but subsequently produced more
      infectious virus and died much faster than control or MoMuLV-infected thymocytes.
      These in vitro studies to some extent reflect our in vivo studies reported
      previously.

PMID- 8560769
TI  - Evidence for phenotypic mixing with reovirus in cell culture.
AB  - From pairwise mixed infections of different reovirus wild-type isolates (T3
      Dearing plus T1 Lang or plus T2 Jones) the progeny virus is phenotypically mixed,
      i.e., progeny viral particles contain proteins derived from both parents but the
      corresponding genes derived from only one parent. Experiments with differential
      inactivation of virus progeny of mixed infections by monoclonal antibodies or by
      33% ethanol reveal phenotypic mixing of two outer shell proteins, sigma 1 and
      probably mu 1. Phenotypic mixing of the mu 1 protein, the product of the M2 gene,
      is a possible explanation for the recent observation of M2 gene-linked dominant
      interference between reovirus isolates.

PMID- 8560770
TI  - Heptad-repeat sequences in the glycoprotein of rhabdoviruses.
AB  - Two or three regions containing three or more successive newly defined heptads of
      a-d hydrophobic amino acid repeats have been located in the cDNA-derived amino
      acid sequences of glycoprotein G of all rhabdoviruses examined (rabies, vesicular
      stomatitis, fish, and plant rhabdoviruses) by computer search. These new heptad
      repeats differ from those previously reported in other viruses because of the
      presence of all the hydrophobic amino acids in positions a or d, and because they
      are not predicted to form coiled coils by current methods and thus they have not
      been detected previously in any rhabdoviruses. The two or three heptad-repeat
      regions were the only parts of the glycoprotein with at least three successive
      heptad-repeats in all the rhabdoviral sequences studied and had low sequence
      variability among the members of each of the rhabdoviral genius but show no
      sequence similarity among the different genus. All these newly detected heptad
      repeats were in the vicinity of some of the higher hydrophobic regions in each of
      the rhabdovirus genera studied and were found mostly, but not always, outside the
      extra amino acid sequences that occur in the longer insect or plant rhabdovirus
      glycoprotein G. The correspondence of position and structure of these heptad
      repeats among all the rhabdoviruses suggests its participation in common
      function(s), most probably related to viral fusion with cellular membranes.

PMID- 8560771
TI  - Baculovirus expression and affinity purification of protein E2 of classical swine
      fever virus strain Alfort/187.
AB  - The genome region encoding the major envelope glycoprotein E2 (gp55) of the
      classical swine fever virus (CSFV) strain Alfort/187 was cloned and sequenced.
      The E2 gene, either with or without additional authentic 5'-terminal sequences
      coding for two variants of a putative signal sequence, was used to construct
      recombinant baculoviruses expressing the respective glycosylated and
      nonglycosylated E2 protein in insect cells. The signal sequences mediated
      glycosylation in insect cells, but no efficient secretion of the protein into the
      cell culture supernatant was observed. Six histidine residues introduced at the
      carboxy terminus of E2 allowed purification of E2 protein by Ni(2+)-chelate
      affinity chromatography. The proteins obtained were characterized and their
      immunological properties were compared by western blot analysis.

PMID- 8560772
TI  - Herpes simplex virus recombination vectors designed to allow insertion of
      modified promoters into transcriptionally "neutral" segments of the viral genome.
AB  - The use of recombinant viruses has been essential in investigation of the biology
      of herpes simplex virus (HSV). In this communication we describe a number of
      viral recombination vectors that we have generated for use in promoter
      structure/function analysis within the context of the HSV-1 genome. We have
      utilized two regions of the HSV genome that contain genes nonessential for
      replication in cultured cells--the glycoprotein C (gC or UL44) locus in the UL of
      the genome and the area encompassing the promoter and 5' portion of the latency
      associated transcript (LAT) within the RL factual influence on promoters due to
      the site of insertion. Two different kinetic promoters were analyzed, those
      controlling expression of the gamma UL 38 and the beta dUTPase genes, in both
      loci. All constructs tested displayed reporter gene mRNA expression with expected
      kinetics, and we conclude that there are no neighboring cryptic promoter elements
      that could interfere with expression studies using the vectors described.

PMID- 8560773
TI  - Identification of the membrane protein of porcine epidemic diarrhea virus.
AB  - Sequence information on the genome of porcine epidemic diarrhea virus(PEDV) has
      only recently been determined. In contrast, very little is known about the viral
      proteins. In the present report we have identified the membrane glycoprotein (M)
      of PEDV by use of rabbit anti-peptide sera and transient expression of the cloned
      M gene in Vero cells and by expression in the baculovirus system. The native M
      protein of PEDV is incorporated into virions, is N-glycosylated, and migrates
      with a relative mobility (Mr) of 27 k in polyacrylamide gels. In contrast, the M
      protein synthesized by recombinant baculoviruses migrates with a Mr of 23 k, that
      is, with identical mobility as the deglycosylated product of PEDV. Thus, it
      appears that M protein specified by the recombinant baculovirus is poorly, if at
      all, glycosylated. Using monoclonal antibodies and rabbit and rabbit antipeptide
      sera specific for the N and C termini of the M protein, we were able to show that
      a 19 k band detected in PEDV-infected cells but not in virions represented a
      fragment of M from which the C terminus had been cleaved off. Finally, by
      electron microscopy and immunogold labelling, the relative orientation of M
      within the virion envelope was determined as NexoCcyt. In conclusion, all of
      these data strongly support the hypothesis that PEDV should be classified with
      the group I coronaviruses.

PMID- 8560774
TI  - A conserved sequence motif at the 5' terminus of the Southampton virus genome is
      characteristic of the Caliciviridae.
AB  - We have determined the 5'terminal cDNA sequence for the genome of Southampton
      virus, a recently characterized, human, small round-structured virus (SRSV).
      Genomic RNA was extracted directly from a stool sample and amplified by RT-PCR by
      homopolymer tailing of the 3' terminus of the cDNA. The additional sequence
      increases the overall length of the Southampton virus genome by 12 nucleotides,
      resulting in a significant change to the genome organization by extending the
      first large open reading frame (ORF) by 51 amino acids. The 5'terminal bases pGpT
      and the presence of conserved genome and putative subgenomic RNA terminal motifs
      are now prominent features shared between the human SRSV Southampton virus and
      the animal caliciviruses rabbit hemorrhagic disease virus and feline calicivirus.

PMID- 8560775
TI  - Molecular analysis of human T-cell lymphotropic virus type II from Wayuu Indians
      of Colombia demonstrates two subtypes of HTLV-IIb.
AB  - Studies of the genetic heterogeneity of human T-cell lymphotropic virus type II
      (HTLV-II) have revealed the presence of two genetic subtypes, termed HTLV-IIa and
      HTLV-IIb. The HTLV-IIb subtype encodes an immunodominant epitope present at the C
      terminus of the extended Tax protein and, by using an LTR-based, restriction
      fragment-length polymorphism (RFLP) assay, can be further classified into IIb60
      IIb5, with HTLV-IIb1 (Central Amerindian-like) and HTLV-IIb5 (North Amerindian
      like) being characteristic subtypes for Native American Indians. To determine the
      antigenic and genetic heterogeneity among HTLV-II-infected South Amerindians, we
      used a Tax synthetic peptide immunoassay on serum, and RFLP and phylogenetic
      analysis on LTR sequences amplified from genomic DNA from four Wayuu Indians of
      Colombia. The Wayuu specimens displayed seroreactivity to the immunodominant
      epitope located in the extended Tax region, as predicted, and demonstrated
      genetic heterogeneity by the presence of both the IIB1 (Wyu1, Zuc31) and IIb5
      (Wyu2, Zuc42) subtypes sequences within separate phylogroups represented by the
      Guaymi Indian (IIb1) and North Amerindian (IIb5) sequences, respectively.
      Sequence analysis showed that major LTR regulatory motifs and the cis-acting
      repressive elements in the LTR RNA secondary structure were relatively conserved
      in both Wayuu subtypes, but the predicted secondary structure of the rex response
      stem loop in the Wyu2 (IIb5) LTR sequence was 45 nucleotides (nt) and 95 nt
      longer than that observed in the Wyu1 (IIb1) and G12.1 (IIb1) LTR sequences,
      respectively. These results extend our knowledge of the genetic heterogeneity of
      HTLV-II in South Amerindians.

PMID- 8560776
TI  - A polycistronic transcript in transformed cells encodes the dihydrofolate
      reductase of herpesvirus saimiri.
AB  - Herpesvirus saimiri, an oncogenic gamma herpesvirus of primates, is the only
      eukaryotic virus that carries the entire metabolic gene set for a complex
      biochemical synthesis. Every element of the thymidine synthesis gene cascade is
      present in the virus, and their function is probably related to the uniquely high
      A + T content of the genome. Although one member of the gene set, dihydrofolate
      reductase (DHFR), is mapped in a region required for oncogenesis, very little is
      known of the expression and function of this gene in transformed cells. We report
      the expression of the DHFR sequence on a novel, unique tricistronic transcript in
      virally transformed tumor cells. The DHFR sequence is the first open reading
      frame on a 5.3 kb minor transcript. Alpha-amanitine sensitivity indicates that it
      is an RNA polymerase II transcript, and since it is also polyadenylated it
      appears to be a functional, relatively unstable (half-life 3 hr) mRNA. Initiation
      of transcription uniquely overlaps with the HSUR3 small RNA gene. Expression of
      the small transcript appears to be alpha-amanitine resistant, implicating
      polymerase III transcription. Together with the remarkably low-level expression
      of HSUR3 in tumor cells, the data may indicate transcription interference between
      two different RNA polymerases, with unusual overlapping regulation and
      initiation.

PMID- 8560777
TI  - Bacteriophage T4 as a surface display vector.
AB  - We describe a method for construction of hymeric bacteriophage T4 particles
      displaying foreign polypeptides on their surface. The method is based on our
      finding that minor T4 fibrous protein fibritin encoded by gene wac (whisker's
      antigen control) could be lengthened at the C terminus without impairing its
      folding or binding to the phage particle. The lengthened fibritin gene could
      easily be transferred into the T4 genome by homologous recombination with a
      plasmid containing the modified gene wac. The modified gene wac is expressed
      properly during phage reproduction, and the lengthened fibritin is bound to phage
      particles. As an example of this type of method, we have obtained the hymeric T4
      particles carrying a polypeptide of 53 residues, 45 of which are from the pre-S2
      region of hepatitis B virus. The T4 display vector extends currently available
      display systems.

PMID- 8560778
TI  - Changes in the hemagglutinin gene of the neurovirulent influenza virus strain
      A/NWS/33.
AB  - The neurovirulent strain of influenza A virus, A/NWS/33, is able to infect a
      large range of cell types, including mouse brain cells, which are not infected by
      its parent, A/WS/33. This seems to be largely due to the hemagglutinin of
      A/NWS/33. The complete nucleotide sequence of the HA genes of both strains has
      been determined and a comparison revealed a number of changes. Analysis showed
      that the virulence capabilities of the NWS HA involve at least three different
      mechanisms: (a) loss of a glycosylation site; (b) a change at the cleavage site;
      and (c) a substitution in HA2, which may increase the pH of fusion.

PMID- 8560779
TI  - Characterization of the hog cholera virus 5' terminus.
AB  - Hog cholera virus (HoCV) 5' terminus of the ALD and GPE(-) strains were analyzed
      by using rapid amplification of cDNA end method (5'RACE). An additional nine
      nucleotides were found at the 5' termini of genomic RNA in the ALD and GPE(-)
      strains of HoCV. These nine nucleotides were also conserved in BVDV and were
      suggested to form a hairpin structure at the 5' terminus by computer-assisted
      analysis. It seems possible that the secondary structure and/or the 5' terminus
      sequence has a significant role in the HoCV virus genome.

PMID- 8560780
TI  - Computer simulations to predict the availability of peptides with known HLA class
      I motifs generated by proteolysis of dengue fever virus (DFV) type 1 structural
      and nonstructural proteins in infected cells.
AB  - Cytotoxic T cells that recognize dengue fever viral (DFV) peptides were reported.
      To predict the cleavage pattern of DFV proteins by cytoplasmic proteasomes into
      nonapeptides with motifs fitting known HLA class I molecules, the computer
      program "Findpatterns" was used. In this study the combined amino acid motifs for
      proteolytic cleavages and the HLA class I haplotype-restricted peptides were
      analyzed. It was noted that putative peptides with motifs of HLA A2 and A68 were
      abundant compared with nonapeptides with motifs HLA A24, B8, B35, and B53. The
      possible interpretation of the computer analysis in explaining the cellular
      immune response in endogenous populations of endemic DF is discussed.

PMID- 8560781
TI  - Sequence of the PV2 gene of rice hoja blanca tenuivirus RNA-2.
AB  - Comparison of a partial sequence of rice hoja blanca tenuivirus RNA-2 with 40%
      similarity to rice stripe tenuivirus RNA-2 revealed regions of high local
      sequence homology at the 5' terminus, within the coding region (the pv2 gene),
      and in the intergenic region separating this gene from the other protein (pc2)
      encoded by this ambisense RNA. Analysis of the conserved regions of the pv2
      protein identified two motifs found principally in viral membrane glycoproteins
      and six motifs found each in a wide variety of proteins. The possible
      significance of these results is discussed.

PMID- 8560782
TI  - Neural network in the transcription-translation process in eukaryotic cells and
      viruses, a comparison.
AB  - The transcription-translation process in the virus-host cell system is analyzed
      in terms of a virtual neural network. In contrast to findings in the
      transcription-translation process in eukaryotic cells, an inverse correlation
      between the frequency of protein amino acids and code degeneracy and between code
      degeneracy and the rate of amino acid substitutions was not found. Misuse of the
      virtual host cell network by virus protein synthesis could be attributed to the
      different amino acid composition of the virus proteins (input unit) studied here.

PMID- 8560783
TI  - HSV-1 brain infection by the olfactory nerve route and virus latency and
      reactivation may cause learning and behavioral deficiencies and violence in
      children and adults: a point of view.
AB  - Two recent studies provided new evidence on the latency of HSV-1 DNA in 15.5% of
      olfactory bulbs and in 72.5% of trigeminal nerves from human corpses at forensic
      postmortems (1) and in 35% of 40 autopsied human brains (2). In the latter
      brains, latent HSV-1 DNA was found in the olfactory bulbs, amygdala, hippocampus,
      brain stem, and trigeminal ganglia. Although in these studies it is not known by
      which route HSV-1 entered the olfactory bulbs and brain, experimental studies in
      mice (3) revealed that injection of HSV-1 into the olfactory bulbs leads to virus
      migration into the brain amygdala and hippocampus via the olfactory nerve and
      locus coeruleus. If the olfactory ciliary nerve epithelium is the port of entry
      of HSV-1 into the olfactory bulbs and brain in humans as well, protection of the
      nose against HSV-1 infection may be needed to prevent virus latency in neurons in
      the amygdala and hippocampus (3). Infection of humans by HSV-1 was estimated to
      increase from 18.2% in the 0-20 year population group to 100% in persons older
      than 60 years (1), indicating that worldwide human populations at all ages are at
      risk of brain infection by the olfactory nerve route. In addition, both primary
      infection and reactivation of latent DNA in the brain may lead to damage of
      neurons in the brain involved in memory, learning, and behavior, as observed in
      infected, acyclovir-treated mice (3). The current introduction of a live
      apathogenic varicella-zoster virus (VZV) vaccine to immunize children against
      chickenpox (4) may suggest that the time is ripe for immunization of children and
      adults against HSV-1 infections, especially infections by the olfactory nerve
      route, to prevent potential brain damage.

PMID- 8560784
TI  - Computer simulations to predict the availability of peptides with known HLA class
      I motifs possibly generated by proteolysis of HIV-1 proteins in infected cells.
AB  - Cytotoxic T cells that recognize HIV-1 peptides generated from all viral proteins
      were reported. To predict the cleavage pattern of HIV-1 proteins by cytoplasmic
      proteasomes into peptides with motifs fitting known HLA class I molecules, the
      computer program Findpatterns was used. In this paper the combined amino acids
      patterns for proteolytic cleavages and the HLA class I haplotype-restricted
      peptides motifs are studied. It was noted that peptides with motifs of HLA class
      I A2 and A68 were abundant compared with HLA class 5B2, B8, B53, and B35.

PMID- 8560785
TI  - Molecular characterization of the 11th RNA segment from human group C rotavirus.
AB  - The complete nucleotide sequence of genome segment 11 from the noncultivatable,
      human group C rotavirus (Bristol strain) was determined. Comparison of the
      nucleotide sequence of the segment termini with the consensus 5' and 3' terminal
      noncoding sequences of the human group C rotavirus genome revealed characteristic
      5' and 3' sequences. Human group C rotavirus genome segment 11 is 613 bp long and
      encodes a single open reading frame of 450 nucleotides (150 amino acids) starting
      at nucleotide 39 and terminating at nucleotide 489, leaving a long 3'
      untranslated region of 124 nucleotides. The predicted translation product has a
      calculated molecular weight of 17.7 kD and contains four potential N-linked
      glycosylation sites. No significant homologies to other viral proteins were found
      in database searches. Hydropathy analysis predicted the human group C rotavirus
      genome segment 11 translation product has a hydrophilic carboxy terminus (amino
      acids 54-150) and a hydrophobic amino terminus (amino acids 1-53) that can be
      further subdivided into three short hydrophobic sequences--H1, H2, and H3. These
      features are analogous to the integral membrane glycoprotein NSP4 encoded by
      group A rotavirus gene 10.

PMID- 8560786
TI  - Long, nearly identical untranslated sequences at the 3' terminal regions of the
      genomic RNAs of cherry leafroll virus (walnut strain).
AB  - Hybridization analyses of cDNA clones derived from the two genomic RNAs, RNA1 and
      RNA2, of the walnut strain of the nepovirus cherry leafroll nepovirus (wCLRV)
      demonstrated a long region of high homology between the two viral RNAs.
      Subsequent mapping and nucleotide sequencing revealed a long, noncoding,
      presumably untranslated, region (3' UTR) immediately 5' of the terminal
      polyadenylate, a region that is almost identical in the two RNAs. This 3' UTR is
      1567 nucleotide residues long in RNA1. Homologies of about 80% were found with
      corresponding regions of genomic RNAs from other strains of CLRV, but not with
      the corresponding regions of other nepovirus genomic RNAs.

PMID- 8560787
TI  - Changes in the neuraminidase of neurovirulent influenza virus strains.
AB  - The influenza virus A/WS/33 has been adapted to mouse brain to produce two
      neurovirulent derivatives, A/NWS/33 (NWS) and A/WSN/33 (WSN), with the viral
      neuraminidase gene shown to be the major determinant of neurovirulence. The
      complete nucleotide sequence of the NA genes from each strain has been
      determined, which has allowed the identification of changes that have occurred
      during adaptation to mouse brain. Five changes are shared by the neurovirulent
      strains. Comparison to the known neuraminidase structure has identified four of
      these that may affect the active site of the enzyme. In addition, significant
      differences in the properties of the neuraminidase from the neurovirulent strains
      were observed relative to the parent strain. While no correlation was observed
      between neurovirulence and overall neuraminidase activity or preference for a
      particular N-substitution, the enzymes from both neurovirulent strains showed an
      increased preference for small substrates and those with 2-->3 linkages, and
      their activity was potentiated by Ca2+ ions.

PMID- 8560789
TI  - Genetic characterization of a new hantavirus detected in Microtus arvalis from
      Slovakia.
AB  - A new hantavirus, called Malacky, has been identified in lung tissue specimens of
      a vole, Microtus arvalis, by the reverse transcriptase polymerase chain reaction
      (RT-PCR). The voles were trapped in a geographical area in Slovakia where
      hemorrhagic fever with renal syndrome (HFRS) is endemic in the human population.
      Sequence analysis of a major part of the S segment showed this virus to represent
      a new subtype within Tula, a new hantavirus genetic group defined very recently.

PMID- 8560790
TI  - Nucleotide sequence of a strain of tobacco etch virus that does not cause Tabasco
      pepper wilt.

PMID- 8560788
TI  - Noncoding control region of naturally occurring BK virus variants: sequence
      comparison and functional analysis.
AB  - The human polyomavirus BK (BKV) has a proven oncogenic potential, but its
      contribution to tumorigenesis under natural conditions remains undetermined. As
      for other primate polyomaviruses, the approximately 5.2 kbp double-stranded
      circular genome of BKV has three functional regions: the coding regions for the
      two early (T, t antigens) and four late (agno, capsid proteins; VP1-3) genes
      separated by a noncoding control region (NCCR). The NCCR contains the origin of
      replication as well as a promoter/enhancer with a mosaic of cis-acting elements
      involved in the regulation of both early and late transcription. Since the
      original isolation of BKV in 1971, a number of other strains have been
      identified. Most strains reveal a strong sequence conservation in the protein
      coding regions of the genome, while the NCCR exhibits considerable variation
      between different BKV isolates. This variation is due to deletions, duplications,
      and rearrangements of a basic set of sequence blocks. Comparative studies have
      proven that the anatomy of the NCCR may determine the transcriptional activities
      governed by the promoter/enhancer, the host cell tropism and permissivity, as
      well as the oncogenic potential of a given BKV strain. In most cases, however,
      the NCCR sequence of new isolates was determined after the virus had been
      passaged several times in more or less arbitrarily chosen cell cultures, a
      process known to predispose for NCCR rearrangements. Following the development of
      the polymerase chain reaction (PCR), it has become feasible to obtain naturally
      occurring BKV NCCRs, and their sequences, in samples taken directly from infected
      human individuals. Hence, the biological significance of BKV NCCR variation may
      be studied without prior propagation of the virus in cell culture. Such variation
      has general interest, because the BKV NCCRs represent typical mammalian
      promoter/enhancers, with a large number of binding motifs for cellular
      transacting factors, which can be conveniently handled for experimental purposes.
      This communication reviews the naturally occurring BKV NCCR variants, isolated
      and sequenced directly from human samples, that have been reported so far. The
      sequences of the different NCCRs are compared and analyzed for the presence of
      proven and putative cellular transcription factor binding sites. Differences in
      biological properties between BKV variants are discussed in light of their
      aberrant NCCR anatomies and the potentially modifying influence of transacting
      factors.

PMID- 8560791
TI  - Coat protein sequence of a resistance-breaking strain of potato virus X isolated
      in Argentina.
AB  - The PVX coat protein (CP) is involved in many aspects of plant-virus interaction
      (virion morphology, plant symptoms, viral pathogenesis and virulence, and genomic
      RNA accumulation). Different virus strains have been distinguished according to
      their compatibility with the host resistance genes Nx, Nb, and Rx. Substitution
      of the Thr 122 on the CP with a Lys in PVX strain HB has been shown to affect the
      response of potato cultivars with the Rx resistance gene. In PVX DX the
      avirulence determinant for the Nx gene has been localized in the Gln 78 of the
      coat. PVX strain MS, like PVX HB, is able to overcome the Rx, Nx, and Nb genes.
      Sequencing of the CP gene of PVX MS (EMBL accession number Z34261) shows that it
      has a Thr in codon 122 and a Gln in codon 78. These results suggest that, in
      addition to the coat protein gene, other regions of the viral genome are involved
      in the pathogenicity.

PMID- 8560792
TI  - Are laws that govern behavior embedded in the structure of the CNS? The case of
      Hering's law.
AB  - The pattern of axonal terminations of individual premotoneuronal medium lead
      burst neurons (MLBs) has been elucidated with the help of the intraaxonal
      recording and horseradish peroxidase injection technique in alert behaving
      monkeys. These findings indicate that individual MLBs do not influence individual
      muscles; instead they influence groups of muscles. Horizontal medium lead burst
      neurons (EBNs) project to ipsilateral lateral rectus motoneurons directly, and
      could contact contralateral medial rectus motoneurons indirectly, through the
      internuclear neurons of the ipsilateral abducens nucleus. Also, upward MLBs
      project to motoneurons innervating both the superior rectus and the inferior
      oblique muscles of both eyes. Finally, downward MLBs project to ipsilateral
      motoneurons innervating the ipsilateral inferior rectus muscle and the
      contralateral superior oblique muscle. All in all, the pattern of oculomotor
      terminations of MLBs provides experimental support for Hering's law of equal
      innervation. EBNs also project to the nucleus prepositus hypoglossi while
      vertical MLBs also project to the interstitial nucleus of Cajal (NIC). These
      structures are thought to participate in the process of "velocity to position
      integration", in the horizontal and vertical planes respectively. Intracellular
      recording from individual neurons of the NIC in alert behaving monkeys followed
      by biocytin or horseradish peroxidase injections demonstrates that their axons
      pass through the posterior commissure on their way to vertical extraocular
      motoneurons. It also demonstrates that these fibers carry a phasic signal related
      to saccades and a tonic signal related to eye position in a precise quantitative
      manner. Work is in progress to determine whether their pattern of oculomotor
      terminations is also appropriate for Hering's law.

PMID- 8560793
TI  - Saccadic eye movement conjugation in children.
AB  - In recent years the conjugacy of the saccadic eye movements has been studied
      extensively in adult humans, while little investigation has been carried out in
      children. We studied the characteristics of binocular saccades in school-age
      children, finding significant differences with adults, particularly in their
      dynamics and binocular coordination. The largest deviations were found in the
      youngest children. An incomplete optimization of the saccadic waveform and a poor
      disconjugate compensation of the mechanical asymmetries of the plants are
      hypothesized to explain the results.

PMID- 8560795
TI  - Theoretical explanations of Listing's law and their implication for binocular
      vision.
AB  - We shall discuss three theoretical explanations of Listing's law for conjugate
      eye movements with the head fixed: the original argument by Helmholtz, which is
      "sensorimotor" in its attempt to optimize vision by using internal feedback from
      the oculomotor system, and two comparatively simple recent explanations based on
      either visual or oculomotor performance. These geometrical demonstrations shed
      some light on recent generalizations of Listing's law to vergent eye movements.

PMID- 8560794
TI  - Binocular alignment and vergence in early infancy.
AB  - Vergence to static targets presented at five distances between 25 and 200 cm from
      the subject was measured in 631 infants aged between 17 and 120 days.
      Photographic images of the eyes were magnified and measured to yield information
      on the monocular and binocular eye positions for each target. Vergence data were
      fit by a linear function and compared to the vergence calculated from target
      distance and each infant's measured interpupillary distance. Differences in
      vergence across targets were also evaluated for each subject by calculating the
      change in angle of rotation for each eye. Many of even the youngest infants
      showed good ocular alignment both monocularly and binocularly, although the
      youngest infants showed the greatest variability in vergence. However, the median
      difference in vergence angle between the eyes for even the youngest group was < 4
      deg (6.8 prism D), and some of this difference is attributed to versional eye
      movements and to slightly off-axis head position across trials. The average
      infant of 1-2 months showed substantially better vergence than has been reported
      in some recent studies. Apparently, oculomotor constraints are not a significant
      barrier to the development of the higher forms of binocularity that begin to
      emerge in the months immediately following the interval studied here, and may
      form the substrate for later developments in binocular vision.

PMID- 8560796
TI  - Rotation of Listing's plane by horizontal, vertical and oblique prism-induced
      vergence.
AB  - We examined the changes in Listing's plane resulting from prismatically induced
      vergence. The three-dimensional angular positions of the two eyes were compared
      in normal subjects wearing search coils and gazing at targets 1.9 m away with and
      without prisms. For horizontal base-out prisms each degree of convergence in one
      eye yielded 0.72 deg of temporal rotation of Listing's plane in that eye. The
      results from vertical prisms were not what was expected from the horizontal
      results. A base-up prism on the right eye induced a downward and temporal
      rotation of Listing's plane. A base-down prism on the right eye induced an upward
      and nasal rotation of Listing's plane. The effects of oblique prisms were those
      expected from combining the effects of horizontal and vertical prisms. Thus in
      addition to producing a horizontal or vertical misalignment of the gaze line,
      prisms induce an unexpected position-dependent torsional disparity.

PMID- 8560797
TI  - Regulation of static and dynamic ocular alignment in patients with trochlear
      nerve pareses.
AB  - Ocular alignment and saccades were studied in seven patients with trochlear nerve
      pareses, before and after strabismus surgery. Prior to surgery, a position
      dependent vertical ocular misalignment was present, and downward saccades were
      hypometric in the paretic eye. Strabismus surgery reduced the magnitude and
      position-dependence of the static misalignment. Saccade conjugacy improved in the
      patients with congenital pareses, and in the patient with a gradual-onset
      acquired paresis, but less improvement occurred in subjects with traumatic
      pareses. The post-operative change in saccade conjugacy relative to the change in
      static alignment correlated with pre-operative vertical vergence, suggesting that
      changes in saccade yoking depend on an interaction between saccades and vertical
      vergence.

PMID- 8560798
TI  - Excess cyclovergence in patients with intermittent exotropia.
AB  - Recently, we developed a model of binocular fixation. This model predicts the
      amount of cyclovergence as a function of target elevation and horizontal target
      vergence. The prediction derives from the assumption that version and vergence
      add linearly and that the eye positions are constrained in three respects: (1)
      the foveae of the two eyes are directed towards the target, (2) the version
      component follows Listing's law, i.e. cycloversion, and horizontal and vertical
      version are not independent, (3) the vergence component is restricted to a plane
      approximately perpendicular to Listing's plane, i.e. horizontal, vertical and
      torsional vergence are not independent. The version and the vergence components
      are characterized by a common primary direction for the two eyes. We applied this
      model to data of patients with intermittent exotropia. In two patients with an
      amblyopic eye we found that the common primary direction rotates towards the
      amblyopic eye. In the third patient, not suffering from amblyopia, the common
      primary direction was practically straight ahead. In all three patients,
      cyclovergence angles were larger than those found in normal subjects. We found
      that the increased cyclovergence was compatible with our model for normal
      subjects if an offset on the horizontal vergence was given. This offset
      represents the additional convergence effort required in these patients to
      overcome the exodeviation of the eyes. According to our model the increased
      horizontal vergence effort results in excess cyclovergence. The relation between
      horizontal vergence and cyclovergence offers a new method for measuring the angle
      of exotropia.

PMID- 8560799
TI  - Plasticity of human motion processing mechanisms following surgery for infantile
      esotropia.
AB  - Monocular oscillatory-motion visual evoked potentials (VEPs) were measured in
      prospective and retrospective groups of infantile esotropia patients who had been
      aligned surgically at different ages. A nasalward-temporal response bias that is
      present prior to surgery was reduced below pre-surgery levels in the prospective
      group. Patients in the retrospective group who had been aligned before 2 yr of
      age showed lower levels of response asymmetry than those who were aligned after
      age 2. The data imply that binocular motion processing mechanisms in infantile
      esotropia patients are capable of some degree of recovery, and that this
      plasticity is restricted to a critical period of visual development.

PMID- 8560800
TI  - Initial directions and landing positions of binocular saccades.
AB  - Existing models for the generation of saccades predict fixed trajectories between
      start and landing positions of saccades. Experimental data show that saccades
      have rather variable trajectories. The objective of the present research is to
      quantify the variability in trajectories of binocular saccades and to test in how
      far spatial variability can be described by adding noise to components of
      existing models. We studied the trajectories of self-paced saccades. Saccades
      were made between a number of stationary, visual targets lying in the frontal
      plane. More than 75 saccades were made to each target. Horizontal and vertical
      movements of both eyes were measured with a scleral coil technique. We defined
      the direction from starting position to end position of each primary saccade as
      the effective direction. We defined the direction from starting position to the
      eye position when the saccade had covered a distance of 2.5 deg as the initial
      direction of the saccade. We find that variability is two to seven times larger
      in initial directions than in effective directions. Effective directions are more
      accurate and more precise than initial directions. For each eye, initial and
      effective directions of saccades made to a particular target are negatively
      correlated, although in most cases rather weakly (0.1 < r2 < 0.5). Contrastingly,
      initial directions are always highly correlated (r2 > 0.8) of associated
      binocular saccades. High correlations are also found between effective
      directions. We conclude that curvedness of saccades is the result of a purposeful
      control strategy. The saccadic trajectories show that, initially, the eyes are
      accelerated roughly in the direction of the target and subsequently they are
      guided to the target. Analysis of possible models suggests that variability
      predominantly enters the saccadic system at a central stage of neuronal saccade
      generation. We conclude from simulations, in which we used different models of
      saccade generation, that the major sources of directional variability are part of
      a feedback loop. This conclusion provides indirect evidence for the presence of a
      feedback loop in the saccadic system.

PMID- 8560801
TI  - Saccade latency toward auditory targets depends on the relative position of the
      sound source with respect to the eyes.
AB  - The latency of saccadic eye movements evoked by the presentation of auditory and
      visual targets was studied while starting eye position was either 0 or 20 deg
      right, or 20 deg left. The results show that for any starting position the
      latency of visually elicited saccades increases with target eccentricity with
      respect to the eyes. For auditory elicited saccades and for any starting position
      the latency decreases with target eccentricity with respect to the eyes.
      Therefore auditory latency depends on a retinotopic motor error, as in the case
      of visual target presentation.

PMID- 8560802
TI  - A field theory of saccade generation: temporal-to-spatial transform in the
      superior colliculus.
AB  - Recent models have placed the superior colliculus inside the local feedback loop
      that generates the pulse of innervation needed to make a saccade. Such closed
      loop models need to take into account the different coordinate systems of visual
      and motor signals. This paper presents a computational model showing how the
      superior colliculus can bring the visual and motor information together in a
      common reference frame.

PMID- 8560803
TI  - Transient torsion during and after saccades.
AB  - In five normal subjects, we analyzed uncalled for torsion (blips) during and
      after horizontal and vertical saccades. Torsion was defined as movement out of
      Listing's plane. During horizontal saccades in downward gaze the abducting eye
      extorted and the adducting eye intorted. The direction of the blips reversed in
      upward gaze. Peak torsional amplitudes (up to 1-2 deg) were always reached during
      saccades; drifts back to Listing's plane outlasted the saccades. Torsion of the
      extorting eye was larger than that of the intorting eye, producing a transient
      positive cyclovergence. Torsion and cyclovergence evoked by vertical saccades
      were also stereotyped in each eye, but showed idiosyncratic differences among
      subjects. We conclude that Listing's law is violated during saccades. Transient
      saccade-evoked torsion might reflect properties of the three-dimensional velocity
      to-position integrator and/or the ocular plant.

PMID- 8560804
TI  - Voluntary binocular gaze-shifts in the plane of regard: dynamics of version and
      vergence.
AB  - We studied the dynamics of voluntary, horizontal, binocular gaze-shifts between
      pairs of continuously visible, real three-dimensional targets. Subjects were
      stabilized on a biteboard to allow full control of target angles, which were made
      to differ only in distance (pure vergence), only in direction (pure version;
      conjugate saccades) or in both distance and direction (disjunctive saccades). A
      wide range of changes in vergence (0-25 deg) and version (0-65 deg) was recorded
      to study the dynamics of disjunctive saccades, described until now for limited
      ranges, throughout the horizontal oculomotor range within manual working space,
      and to study the velocity-duration-amplitude relations ("main sequence") of
      disjunctive vs conjugate saccades. Pure vergence was almost never observed;
      divergence, especially, was always associated with saccades. Likewise, horizontal
      saccades were never strictly conjugate, they always contained a transient
      divergence-convergence sequence. The amplitude and velocity of these transient
      components varied systematically with saccadic size. In combined version-vergence
      movements, vergence was, in general, accelerated and shortened as a function of
      increasing version. This effect was fairly uniform for divergence, which appeared
      to increase in velocity by about as much as the transient peak divergent velocity
      of the version saccade. The intrasaccadic fraction of divergence increased from
      about 50% to close to 100% as a function of increasing version. For convergence,
      saccades up to about 20 deg were also accelerating; in this case it appeared as
      if the transient peak convergent velocity of the version saccade was added to the
      basic convergence velocity. For larger saccades this effect was partly
      counteracted by the penetration of an initial divergence associated with the
      saccade. This initial divergence delayed and slowed down convergence. The
      intrasaccadic fraction of convergence varied between about 40% and 70%. In
      disjunctive saccades the individual eyes did not follow the main-sequence
      parameters of conjugate saccades of comparable sizes, except for the eye that
      moved with the combination "abduction and divergence". For all other combinations
      of vergence and version, disjunctive saccades had lower peak velocities and
      longer durations than conjugate saccades. As a consequence, disjunctive version
      was also slower than conjugate version. Thus, while version accelerates vergence,
      vergence slows down version: in the generalized case of three-dimensional gaze
      shifts, peak velocities and durations are in between those of the limiting cases
      of pure version and pure vergence. We conclude that, within manual working space,
      binocular gaze-shifts are effected by the highly integrated action of conjugate
      and disjunctive mechanisms, both of which are expressed preferentially in fast,
      saccadic movements.

PMID- 8560805
TI  - Providing distinct vergence and version dynamics in a bilateral oculomotor
      network.
AB  - Given reported interactions between vergence and version dynamics, ocular
      reflexes cannot be properly modelled as separate independent subsystems. Using a
      model structure compatible with known anatomy, we show that a single bilateral
      system can produce results consistent with observed data both at the central and
      ocular levels. This model provides for both vergence and conjugate integrators in
      a single controller, and explains the observed modulation on abducens
      interneurons and mesencephalic vergence cells during vergence responses. Reported
      interactions between version and vergence would then be a natural consequence of
      a shared premotor network. Major implications include: the need to record both
      eyes in a protocol, since cross-talk is always possible; and adaptation to
      monocular changes could be distributed in all motor projections to both eyes.

PMID- 8560806
TI  - Gap-overlap effects on latencies of saccades, vergence and combined vergence
      saccades in humans.
AB  - We examined the effect of gap-overlap stimuli on the distribution of latencies
      for pure saccades, pure vergence and combined saccades and vergence in three
      normal subjects. With the gap stimulus, a distinct peak of "express saccades"
      occurred, both with and without associated vergence, but a distinct "express
      vergence" response was not identified. Nevertheless, with the gap stimulus there
      was a decrease in vergence latencies (17 msec), but less so than for saccades (41
      msec). In the combined paradigm the gap effects on saccades and vergence
      resembled those for each component made alone. In addition, the latencies of the
      saccade and vergence components were linearly correlated with an average slope of
      0.5. To explain these results we suggest that there is common signal processing
      at an early stage of saccade and vergence initiation, which is followed by
      activity that builds in separate trigger mechanisms that can be influenced by the
      conditions of fixation.

PMID- 8560808
TI  - The function of visual search and memory in sequential looking tasks.
AB  - Eye and head movements were recorded as unrestrained subjects tapped or only
      looked at nearby targets. Scanning patterns were the same in both tasks: subjects
      looked at each target before tapping it; visual search had similar speeds and
      gaze-shift accuracies. Looking, however, took longer and, unlike tapping,
      benefitted little from practice. Looking speeded up more than tapping when memory
      load was reduced: memory was more efficient during tapping. CONCLUSION: eye
      movements made when only looking are different from those made when tapping.
      Visual search functions as a separate process, incorporated into both tasks: it
      can be used to improve performance when memory load is heavy.

PMID- 8560807
TI  - Initiation of disjunctive smooth pursuit in monkeys: evidence that Hering's law
      of equal innervation is not obeyed by the smooth pursuit system.
AB  - Monkeys generated disjunctive smooth pursuit eye movements when they tracked
      visual targets that moved toward or away from them. Eye acceleration was computed
      during the initial 100 msec of pursuit (the open-loop interval) for various
      target trajectories. The initial acceleration of either eye was a function of the
      target's motion with respect to that eye, regardless of whether or not the
      pursuit was conjugate or disjunctive, or performed with one eye occluded. Eye
      movements produced by fusional vergence could be separated temporally from eye
      movements produced by smooth pursuit using step-ramp paradigms. The separation of
      the two responses demonstrates that the fusional vergence system operates in
      parallel with the smooth pursuit system, presumably to minimize disparity, but
      not to generate disjunctive components of smooth pursuit eye movements.

PMID- 8560809
TI  - Analysis of saccadic short-term plasticity in three dimensions.
AB  - The capacity for short-term adaptation is a well-established property of the
      horizontal (H) and vertical (V) components of saccades. It allows these
      directional components, which clearly serve the goal of foveation, to maintain
      their precision even under changing circumstances. Torsional (T) saccade
      components, on the other hand, which deal with the orientation of the target on
      the fovea, have hardly been investigated in adaptation experiments. They appear
      to be severely restricted by Listing's law during fixations and saccades. The
      main purpose of Listing's law is far from obvious but could be visual or
      oculomotor. Better knowledge of the adaptive capacity of the saccadic system in
      the torsional direction could throw new light on the functional significance of
      this interesting neural strategy. To study short-term plasticity in the torsional
      components of saccades, binocular 3D-eye positions were measured, using magnetic
      search coils. Five normal human subjects were instructed to make uni-directional
      refixation saccades, while they viewed a large visual scene. To induce a change
      in the torsional component, the complete stimulus was rapidly rotated during
      these saccades. We thoroughly investigated the torsional responses of the
      saccadic system, to see if any short-term adaptive response in torsional
      direction was induced, in which case the notion of a visual purpose for Listing's
      law would be strengthened. In none of our experiments, however, did we find any
      clear adaptive response in torsional direction. To further investigate the
      reliability of this result and to ascertain that our experimental conditions
      allowed classical gain adaptation, we also did experiments designed to achieve a
      combination of torsional adaptation and classic gain shortening in one of the
      directional components. While gain adaptation was very obvious, none of the
      experiments provided evidence for a short-term effect in torsion. We conclude
      that our experiments do not support a purely visual basis for Listing's law.

PMID- 8560810
TI  - Binocular interactions in rapid saccadic adaptation.
AB  - An adaptive mechanism controls the strength of innervation to the two eyes
      independently. However, under some circumstances an adjustment in strength of
      innervation to one eye is generalized to the other. The coupling and uncoupling
      of the two eyes during saccadic motor learning was studied using the technique of
      intrasaccadic target displacements to provide a precise visual-motor error
      proportional to the commanded movement. Early adaptive changes (saccade plus fast
      vergence) were measured within the saccadic interval and late adaptive changes
      (vergence error) were measured after the saccadic interval. When one viewing eye
      was retrained using intrasaccadic displacements, saccadic amplitude changes
      generalized to the other nonviewing eye. Thus, rapid adaptive changes trained
      monocularly were transferred to the nonviewing eye. But when two eyes were
      viewing and an adaptive stimulus was provided to only one eye (binocular viewing
      monocular training), adaptive changes also occurred in both eyes. Experiments
      described here suggest that the recalibration of the saccade occurs quickly as a
      conjugate adjustment of gain which is used to balance innervation to the two
      eyes. Thereafter, disconjugate mechanisms provide a further recalibration to each
      eye independently.

PMID- 8560811
TI  - Rapid gain adaptation affects the dynamics of saccadic eye movements in humans.
AB  - The effect of rapid gain adaptation on the dynamics of visually guided saccades
      was investigated in six human subjects by using a search coil system. Saccadic
      adaptation was induced artificially by dislocating the target (by about 30% of
      the initial step) either forward (gain increase) or backward (gain decrease)
      during the primary saccade ("double-step paradigm"). Duration, peak velocity and
      peak acceleration and deceleration of a "standard 12 deg saccade" were computed
      from the data and were compared for the conditions of gain decrease, gain
      increase and the control without gain adaptation. The gain as well as the peak
      velocity and duration of the saccades showed an increased variability during the
      adaptation. In general, the abducting saccades had a higher peak acceleration
      than the adducting saccades, and all subjects showed an idiosyncratic pattern of
      the acceleration and deceleration. In the gain increase paradigm the subjects
      showed an increase in the duration and a decrease in the peak velocity. In the
      gain decrease paradigm there was a significant smaller ratio of peak
      acceleration/peak deceleration compared to the gain increase and the control
      condition. The findings demonstrate that rapid gain adaptation influences the
      dynamics of saccades in a specific way: peak saccadic velocity decreases and
      duration increases in the gain increase paradigm and peak acceleration/peak
      deceleration decreases in the gain decrease paradigm. Moreover, these results
      also suggest that the deceleration is neuronally controlled and not merely a
      result of mechanical constraints.

PMID- 8560812
TI  - Unequal amplitude saccades produced by aniseikonic patterns: effects of viewing
      distance.
AB  - This study describes differences in horizontal and vertical disconjugate saccades
      under far and close viewing conditions of two dichoptically presented aniseikonic
      random checkerboard patterns. At far viewing, disconjugacy of horizontal saccades
      requiring divergence was accomplished intrasaccadically after several minutes;
      for convergence the intrasaccadic disconjugacy was limited. Size differences
      partially persisted in open-loop trials. At close viewing intrasaccadic divergent
      changes in conjugacy were instantaneous, but motor storage during open-loop was
      absent. It is concluded that disconjugate saccades to targets at far distance
      lead to an adaptation process, whereas at close viewing distance horizontal
      disparity is a visual compensation process used directly to scale the relative
      amplitudes of both eyes, not leading to adaptation. The time-course of
      disconjugate vertical saccades was much slower, with mostly postsaccadic
      vergence. Nearby viewing enhanced the disconjugacy of vertical saccades.

PMID- 8560813
TI  - Unequal saccades produced by aniseikonic patterns: a model approach.
AB  - This study addresses a possible mechanism for fast disconjugate adaptation of
      binocular horizontal saccades. Disconjugacy of binocular saccades was elicited by
      two dichoptically presented, identical but aniseikonic, random checkerboard
      patterns. Adaptation was achieved with the patterns at far distance (144 cm). In
      this condition, which requires a relatively small (8%) size difference of the
      saccades, a short learning period was mandatory for the binocular saccades to
      become disconjugate. The saccadic modifications were superimposed on an
      idiosyncratic pattern of intra-saccadic yoking. A model of saccadic signal
      generation is described, that has been used to separate the contributions on
      saccadic disconjugacy provided by modification of visual inputs processing, which
      alters the motor-system inputs, and by modification of the control system: the
      adaptation. We identified three major components of the saccadic command (two
      phasic and one tonic) that contribute and in a specific way to the saccadic
      yoking and disconjugacy. The model analysis proposes that separate control
      mechanisms exist operating on these phasic and tonic signals. We show that the
      saccadic system can generate the vergence component shown by our aniseikonic
      saccades. We discuss a distributed-parallel implementation of the saccadic system
      able to provide both the conjugate and disconjugate components of control.

PMID- 8560814
TI  - Position dependency of rapidly induced saccade disconjugacy.
AB  - We tested the ability of normal subjects to alter the conjugacy of their saccades
      in a position-specific manner. Five subjects dichoptically viewed a stereogram
      produced by two random-dot patterns. They immediately perceived a three
      dimensional wedge with its apex closer to them. They were asked to saccade for 15
      min back and forth between the apex and two lateral dots of the wedge. For
      fixation sequences between centre-right-centre, saccades immediately became
      larger in the right eye. For sequences between centre-left-centre, saccades
      immediately became larger in the left eye. For two subjects this non-monotonic
      position-specific disconjugacy compensated for the disparity of the stereogram
      almost perfectly. The disconjugacy persisted even under monocular viewing of one
      of the random-dot patterns. It diminished or disappeared immediately, however,
      when the random-dot pattern was shifted on the screen. We suggest the existence
      of a fast learning mechanism capable of producing position-specific disconjugacy
      by associating saccades with disparity. Such a mechanism would use a visual
      reference rather than the position of the eyes in the orbit.

PMID- 8560815
TI  - Immediate saccade amplitude disconjugacy induced by unequal images.
AB  - We tested the ability of normal subjects to make changes in the conjugacy of
      their saccades. Subjects dichoptically viewed a grid the size of which was 10%
      larger in one eye. The grids were centred onto a flat screen at 57 cm or 1 m from
      the subject. Horizontal saccades immediately became larger in the eye viewing the
      larger grid. For some subjects this disconjugacy persisted even under subsequent
      monocular viewing. Such persistent changes occurred mainly in the field where the
      required disconjugacy was divergent for centrifugal saccades, convergent for
      centripetal saccades. Vertical saccades also developed compensatory disconjugacy;
      its amplitude was smaller but less variable. To explain these results we propose
      a fast associative learning mechanism that pairs peripheral disparity with
      saccades and is capable of producing saccade disconjugacy even in the absence of
      disparity. For horizontal saccades a secondary conditioning of monocular depth
      cues by the disparity would also be involved.

PMID- 8560816
TI  - An adaptable association between vertical and horizontal vergence.
AB  - Vertical phoria (vergence error under monocular viewing conditions) can be
      trained to vary with conjugate eye position. The adaptive response controls the
      vertical alignment of the two eyes in the absence of binocular disparity and is
      used to compensate for binocular changes of the oculomotor system induced by
      developmental and environmental factors. Vertical phoria was associated with
      horizontal disparity vergence by adapting vertical vergence to two vertically
      disparate targets separated along the depth axis. This association was primarily
      dependent on the horizontal vergence as opposed to monocular eye position or
      binocular conjugate eye position. Following this adapted association with
      horizontal disparity vergence, vertical phoria aftereffects were also evoked by
      accommodative vergence. Previous reports have demonstrated an adapted association
      between vertical phoria and conjugate eye position. The current report examines
      the difference in the vertical phoria resulting from adaptation to vertically
      disparate targets separated along either the vertical axis or depth axis. The
      amplitude of the vertical vergence aftereffect was approximately 4 times greater
      for targets separated along the depth axis than in the vertical meridian. The
      association between vertical phoria with conjugate eye position and horizontal
      vergence is proposed to result from a cross-coupling of vertical vergence with
      supranuclear regions that control conjugate and horizontal vergence eye
      movements. A selective interaction would enable the oculomotor system to correct
      disturbances in specific supranuclear regions as they interface with vertical
      vergence.

PMID- 8560817
TI  - Separate adaptive mechanisms for the control of reactive and volitional saccadic
      eye movements.
AB  - Adaptive reduction of the gain of the saccadic system was induced by means of two
      basically different paradigms. In the first approach the subjects had to follow a
      step-wise moving target. During each follow-up saccade the target was
      systematically displaced by 25% of the initial step, into the opposite direction
      of the saccade. In the second approach the subjects scanned a display of six
      small items. During each scanning saccade the whole display was displaced by 25%
      into the opposite direction of the saccade. Both conditions lead to fast and
      consistent saccadic gain reductions. However, adaptation with the stepping target
      did not transfer to the saccades in the scanning situation, nor to delayed
      saccades in an overlap paradigm, nor to memory-guided saccades. Conversely, when
      saccades were adapted in the scanning situation, induced gain changes transferred
      to overlap and memory-guided saccades, but not to saccades following steps of a
      single target. The results suggest that two separate and largely independent
      mechanisms are involved in the generation of reactive, stimulus-triggered and
      volitional, internally generated saccades, respectively. Both types of responses
      can be selectively adapted.

PMID- 8560818
TI  - [Mechanisms of the favorable effect of spinal anesthesia in traumatic shock].
AB  - Changes in the level of total peptidoleukotriens-pLT (LTC4 + LTD4 + LTE4) and
      inositol triphosphates (IP3) were analyzed in the thalamus of rats subjected to
      "tourniquet" trauma of both hind extremities (LD50) depending on the power of
      afferent nociceptive nerve impulses. Prevention of spreading, i.e., reduction of
      painful impulses from the damaged regions was achieved by the spinal anesthesia
      with bupivacain-chloride immediately after removal of the rubber bandage.
      Together with pLT and IP3 levels determined by radio immunoassay, physiologic
      parameters (mean arterial pressure, blood-brain barrier permeability) were also
      analyzed. Morphologic changes in the thalamus of rats were analyzed by electron
      microscopy. Extreme increase of the thalamic pLT and IP3 levels in traumatized
      animals together with increased blood-brain barrier permeability were found.
      Spinal anesthesia prevented, i.e., reduced these pathologic changes. Authors
      conclude that afferent painful impulses cause pLT increase in the thalamus and
      could modify CNS response to the trauma.

PMID- 8560819
TI  - [Mortality in the most common malignant tumors in women in Serbia].
AB  - The incidence and mortality rate due to the most common malignant tumors in women
      in Serbia 1982-1991 were presented. Records from the Republic Institute of
      Statistics were used as the source of data. Descriptive method was used in
      epidemiological analysis. Within the period 1982-1991, women in Serbia had died
      most frequently due to malignant tumors of breast, lung, cervix, rectum, liver,
      colon, ovary, pancreas and uterine body. Tendency towards increased mortality
      rate due to the cancer of the breast, cervix, ovary, pancreas, rectum and colon
      has been registered in this period. Reduced mortality rate was observed in the
      cancers of uterine body, liver and stomach.

PMID- 8560820
TI  - [Lateral humeral epicondylitis].
AB  - Incidence of the epicondylitis humeri lateralis in a sample of 48 patients was
      analyzed according to age groups. The highest incidence was found in the age
      group of 21-30 that corresponds to the etiologic factor of more intensive work
      with extended arm and clenched hand, practiced by tennis players, bricklayers,
      house painters, etc. The incidence in soldiers was insignificant. Patients were
      treated conservatively. There were no severe cases requiring operative treatment.
      Success was achieved by deep subtendinous and subperiostal infiltration of
      corticosteroids with 0.5 or 1% Novocain around the affected area. Infiltration
      was performed in 7-day intervals and the best result was achieved after the
      second one.

PMID- 8560821
TI  - [The effect of therapeutic plasma exchange on serum immunoglobulins and the
      clinical course of myasthenia gravis].
AB  - Fourteen patients with clinically, pharmacologically and electrophysiologically
      confirmed myasthenia gravis in which therapeutic plasma exchange was performed
      were analyzed. Condition of these patients was assessed before and after the
      plasma exchange using the Besinger score. The serum immunoglobulin levels were
      also determined by ELISA-test before and after the plasma exchange. Findings have
      shown that clinical improvement was highly significant. Changes in IgM and IgA
      levels were significant, but not in IG and IgE. Significant correlation neither
      between the level of each separate immunoglobulin and clinical condition of the
      patient, nor between the change in the level of each separate immunoglobulin and
      changed clinical course was found after the series of plasma exchange. Cumulative
      effect of all immunoglobulins was not observed due to differences in their
      physical and chemical properties. Absence of significant statistical correlation
      between the level of each immunoglobulin and clinical condition of the patient as
      well as between the level changes of each separate immunoglobulin and changed
      clinical condition after series of plasma exchange could be explained by
      cumulative effect of all immunoglobulins, but probably also by the presence of
      some other, circulating factor not belonging to the class of immunoglobulins and
      associated with the development of myasthenic weakness.

PMID- 8560822
TI  - [The role of nitric oxide in physiologic functions and pathologic conditions].

PMID- 8560823
TI  - [Rehabilitation of drug addicts].

PMID- 8560824
TI  - [Erythropoietin--physiology and therapeutic use].

PMID- 8560825
TI  - [Therapy of epilepsy with stimulation of the vagus nerve].

PMID- 8560826
TI  - [The first cases of tularemia in Vojvodina].

PMID- 8560827
TI  - [Mixed cryoglobulinemia in chronic virus diseases of the liver].

PMID- 8560828
TI  - [Pseudomalignant myositis ossificans as a diagnostic problem].

PMID- 8560829
TI  - [Glomerulonephritis and infected ventriculoatrial shunt in hydrocephalus (shunt
      nephritis)].

PMID- 8560830
TI  - [The effect of gammaphos on the course and outcome of surgical treatment in
      combined radiation injuries in pigs].
AB  - The effect of gamaphos (0.6 mmol kg-1 im, 20 min before irradiation) was
      investigated upon the course and outcome of the surgical management of combined
      radiation-gunshot injury in pigs. The hypothesis was tested that the infliction
      of perforating gunshot injury (LD0/30 days) in pigs in the latent phase of the
      acute radiation injury (LD0/30 days) results in the increase of the lethal
      outcome. Gamaphos treatment prevented the lethal outcome. Besides, wound
      reepithelization and granular tissue vascularization in protected pigs was more
      intensive in comparison with the unprotected ones.

PMID- 8560831
TI  - [Neuromodulation of synaptic transmission with thymopentin].
AB  - The effect of thymopentin (TP-5; 1 x 10(-5) and 1 x 10(-4) M), the active center
      of the thymic hormone thymopoietin was examined upon spontaneous and induced
      neuromuscular synaptic activity (N-MS) in the isolated diaphragm of Wistar-strain
      rat. Standard electrophysiological method of intracellular registration was used.
      Analysis of original experimental microphysiologic results revealed clear
      depressant neuromodulative effect of TP-5 upon skeletal N-MS in vitro. Effect of
      TP-5 is expressed in decreased amount of the released median quantal value of
      neurotransmitter acetylcholine at orthodromic stimulation of the alpha-motor
      nerve. TP-5 also reduces chemiosensitivity of postsynaptic nicotinic
      acetylcholine receptors.

PMID- 8560832
TI  - [Sensitivity of electrophysiologic tests in the diagnosis of carpal tunnel
      syndrome].
AB  - According to anatomic characteristics of median nerve branches and
      pathophysiological basis of the carpal tunnel syndrome (CTS), significant
      difference in sensitivity of some electrophysiological parameters in the
      diagnosis of this syndrome was presumed. The aim of this study was to analyze
      characteristics of some abnormalities of electrophysiological parameters and to
      determine their frequency in the carpal tunnel syndrome. Investigation was
      performed on 34 patients with the carpal tunnel syndrome and 30 neurologically
      healthy subjects. EMGs of the tenar muscles, terminal latency parameters for the
      median nerve and sensory conductivity of the median nerve branches including
      cutaneous palmar branch and ulnar nerve branches of the ring finger were examined
      and analyzed. Results have shown that abnormalities were most frequently found in
      sensory conductivity parameters for median nerve branch of the ring finger.
      Significant difference between sensory conductivity parameters for cutaneous
      palmar branch and median nerve branch of the thumb was also found. These results
      were discussed in terms of current knowledge about anatomic characteristics of
      the hand innervation and pathophysiology of the carpal tunnel syndrome. It was
      concluded that the most frequent physiological findings could be used as a highly
      sensitive test for reliable and early diagnosis of CTS.

PMID- 8560833
TI  - [Incidence and localization of deep venous thrombosis and disorders of pulmonary
      perfusion in patients after surgery in colorectal carcinoma].
AB  - In 50 patients aged 60 +/- 4 operated for colorectal carcinoma simultaneous
      combined radionuclide phlebography (RNP) and pulmonary perfusion scintigraphy
      (PPS) using 99Tcm labeled macroaggregates of the human serum albumin (MAHSA) were
      performed within 20 postoperative days aiming to detect deep vein thrombosis
      (DVT) and pulmonary thromboembolism (PTE). The aim of the study was to determine
      the incidence and segmental DVT localization as well as incidence, localization
      and clinical characteristics of developed pulmonary perfusion disorders. Deep
      vein thrombosis was detected in 33 (66%) patients with rather uniform
      distribution in vein segments. According to their scintigraphic characteristics
      the findings suggested recent thrombosis in almost all cases (only two of them
      had signs of chronic thrombosis). Of patients with detected DVT 17 (52%) had
      pulmonary perfusion disorders of which 10 (59%) were unilateral (7 right and 3
      left) and 7 (42%) bilateral. Characteristics and extent of perfusion defects
      suggested very probable PTE in 11 (65%) patients and less probable in 6 (35%). It
      has been concluded that patients operated for colorectal carcinoma were highly
      exposed to DVT and PTE development which necessitates all measures contributing
      to their prevention.

PMID- 8560834
TI  - [The effect of indobufen on patency in femoro-popliteal/crural bypass using
      artificial grafts].
AB  - The aim of this clinical prospective study was to determine the effect of
      indobufen upon synthetic graft patency in femoral-popliteal/crural position. 15
      operated patients were observed during the three-month period. One day prior to
      operation patients were given 400 mg of indobufen perorally. The same daily dose
      was continued on the first postoperative day as well as during the following
      three months. Blood levels of 6-keto-prostaglandin (PG) F1alpha (stable
      metabolite of PGI2) and thromboxane (Tx) B2 (stable metabolite of TxA2) were
      determined by RIA before indobufen administration, i.e., one day and three months
      postoperatively. The three-month patency of grafts was achieved in 86% of cases.
      Plasma levels in all observed time periods showed significantly reduced TxB2,
      increased 6-keto-PGF1alpha, and higher PGI2 levels compared with TxA2 that could
      suggest the normalization of aggregation/antiaggregation process.

PMID- 8560835
TI  - [Use of the Hemoccult Test in the detection of colorectal cancer].
AB  - Hemoccult-test was performed in 3,000 inhabitants of Ruma aged 40-75 years. The
      response rate was 94%. Hemoccult was positive in 2% of cases. After detailed
      diagnostic procedures (rectosygmoidoscopy, colonoscopy or double-contrast
      irrigography) colerectal carcinoma was found in 3 and polyps in 6 subjects.
      Positive predicted value was 5.3% for colorectal cancer and 10.7% for polyps. Due
      to the used methodological approach our study failed to answer the question
      whether early detection of colorectal carcinoma by Hemoccult-test influenced the
      reduction of mortality rate in this malignoma, but it revealed the motivation of
      examined population for early detection of the colorectal cancer.

PMID- 8560836
TI  - [Diagnostic value of electroencephalography and evoked potentials in monitoring
      brain maturation in children with febrile convulsions].
AB  - A group of 31 children aged 4-14 was presented with clinical manifestations of
      febrile convulsions, which after clinical examination, were followed--up in
      outpatient clinics during 1-12 year period. Together with continuous
      electroencephalographic monitoring, visual and somatosensory potentials were
      measured with the aim to stress a diagnostic significance of these
      neurophysiological methods for cerebral maturation assessment in children with
      febrile convulsions. Results reveal that electroencephalography (EEG) and
      somatosensory potentials (SEP) have higher diagnostic sensitivity compared to the
      visual ones (VEP). In 25 children (80.64%) SEP changes were registered in the
      form of prolonged central conductivity time (CCT) and EEG revealed changes in the
      form of slower cerebral activity and posterior theta activities fr. 4-7 Hz (P-O
      bilaterally) in 10 children (32.26%). Registered SEP changes, particularly
      prolonged CVP, as well as changes in the form of slower basic cerebral activity
      or posterior theta rhythm could be explained by slower maturation of some CNS
      regions. EEG and SEP findings show positive correlation with clinical findings
      and different diagnostic sensitivity, therefore their use in clinical follow-up
      of children with febrile convulsions is important.

PMID- 8560837
TI  - [Effect of a reducing diet and physical activity in obese individuals with
      arterial hypertension].
AB  - The effects of reducing diet of 4.4 MJ with reduced daily sodium chloride intake
      and physical activity (walking and floor exercise) in 90 patients of the
      Counseling office for Dietetics (23 males and 67 females) with excessive obesity
      and arterial hypertension (AH) were examined. Although both groups of patients
      were of the similar nutritional status, rate of the body mass loss during the
      diet was significantly higher in males (p < 0.05). At the end of the diet
      therapy, beside reduced body mass, significantly lower average systolic and
      diastolic pressure (p < 0.01) was observed in both sexes. Correlation analysis
      showed significant positive correlation between the weight loss rate and reduced
      diastolic pressure (p < 0.05) only in females.

PMID- 8560838
TI  - [Critical approach to antibiotic therapy in Lyme disease].

PMID- 8560839
TI  - [Differential diagnosis of disorders of neuromuscular transmission: myasthenia
      gravis and myasthenic syndrome].

PMID- 8560840
TI  - [Identification of Toxocara canis larvae in ocular granuloma].

PMID- 8560841
TI  - [The anorexia nervosa syndrome].

PMID- 8560842
TI  - [Sensitivity of atherosclerosis indices in patients with ischemic brain disease].
AB  - Epidemiological studies suggest that dyslipoproteinemias and
      hyperlipoproteinemias present one of the most important risk factors in the
      development of atherosclerosis and its complications. The aim of this study was
      to find out which of the lipid status disorders in patients with ischemic brain
      disease was the most important risk factor in the development of cerebral
      atherosclerosis. Patients with ischemic brain disease were examined in the acute
      and subacute phase. Total blood cholesterol, low density lipoproteins (LDL) and
      high density lipoproteins (HDL) as well as of apolipoproteins A1 and B were
      determined. Correlations (atherogenic indices) of some lipid components with the
      severity of clinical course and echo-angiographic finding were determined. It was
      concluded that the highest correlation with the cerebral atherosclerosis severity
      degree existed with the level of apoA1 and apoB apolipoproteins, followed by
      correlation of LDL and HDL cholesterol, and the lowest correlation was found
      between HDL and the total cholesterol. Accordingly, apolipoproteins, i.e.,
      apoA1/apoB indices are the most sensitive markers of the risk for atherogenesis.

PMID- 8560843
TI  - [Distribution of p27 and gp70 feline leukemia virus antigens in various tissues].
AB  - Application of immunocytochemical methods (DP, IP, PAP, APAAP and IP-IP) has
      confirmed the existence of p27 and gp70 feline leukosis viral antigens (FeLV) in
      various tissues of 22 cats. Both viral antigens were found in bone marrow stem
      cells, but p27 antigens were mostly found in epithelial cells of intestinal
      crypts. In splenic T-lymphocytes and mediastinal lymph nodes the predominance of
      gp70 antigens in FeLV was confirmed, while the tropism of leukosis viruses in the
      lung was inclined to epithelial cells of bronchial glands where p27 antigens were
      dominant.

PMID- 8560844
TI  - [Personal experience in the treatment of chronic viral hepatitis B with
      recombinant interferon B alfa-2].
AB  - Twelve patients were treated with alpha-2 recombinant interferon during 4 months.
      Patients were given daily dose of 3 million units three times a week. Therapeutic
      effect expressed as the percentage of HBeAG seroconversion or by the loss of
      antibodies for the core antigen in IgM fraction and by the core antigen loss from
      hepatic tissue, was achieved in 41.6% of patients. Corticosteroids, administered
      before interferon, could improve therapeutic effect. Better response to therapy
      was observed in patients with higher serum transaminase levels and with
      histopathologically confirmed chronic hepatitis. Predictive value of each
      immunological parameter of therapeutic effect requires further study.

PMID- 8560845
TI  - [Significance of renal biopsy in patients with isolated microhematuria].
AB  - Retrospective study included 30 patients with isolated microhematuria in which
      renal biopsy was performed. Renal biopsy provided diagnosis in 28 (98.3%) cases,
      and histological finding was normal in only 2 (6.7%) patients. The most frequent
      finding was IgA nephritis found in 15 (50%) patients, while the other forms of
      glomerulonephritis were less frequent. In our patients there were no indications
      for steroid therapy. It was concluded that renal biopsy had great diagnostic
      value and that it should be preferred to invasive urologic-radiologic diagnostic
      procedures particularly when it is to be performed transcutaneously.

PMID- 8560846
TI  - [Clinical and morphologic characteristics of adult IgA nephropathy].
AB  - Within the period 1987-1992 IgA nephropathy was diagnosed at the Nephrology
      Clinic of the Military Medical Academy in 61 patients aged from 17 to 41 years
      (mean +/- SD = 24.31 +/- 6.39). The aim of the study was to evaluate their
      importance as markers of progressive forms of IgA nephropathy by analysis of
      mutual relationship of clinical-laboratory and histopathological characteristics.
      Clinical form of the disease with recurrent macroscopic hematurias existed in 30
      (49.2%) patients, and oligosymptomatic form in 31 (50.8%) patients. Acute renal
      failure of reversible oliguric character had 5 (8.2%) patients. Patients with
      recurrent macroscopic hematurias had more progressive course of IgA nephropathy
      which could be indirectly seen from the parameters of the global renal function.
      The most frequent histological form of IgA nephropathy was diffuse
      mesangioproliferative glomerulonephritis registered in 30 (49.2%) patients.

PMID- 8560847
TI  - [Anatomic characteristics and clinical signs of congenital anomalies in the
      circle of Willis].
AB  - Anatomical characteristics and clinical importance of congenital anomalies of
      cerebral arteries were examined based on the results obtained by dissection of
      the circle of Willis blood vessels of 70 native cadaveric brains. Anomalies were
      most frequently found in posterior communicant artery and their most frequent
      type was hypoplasia of the blood vessel. Multiple anomalies of the circle of
      Willis were found in 3 cadavers. Premortal neurological symptomatology (PNS)
      existed in 5 cadavers. There was no significant difference in PNS occurrence at
      autopsy in cases with or without anomalies. Association of aneurisms with
      anomalies of the circle of Willis was found in two cases, but it was not
      significant in comparison to the control group with no anomalies.

PMID- 8560848
TI  - [Epidemiologic-anamnestic study of stomach cancer in relation to nutrition].
AB  - Correlation between the disease and nutritional habits was evaluated in this
      epidemiologic-anamnestic study. It included 80 patients with the confirmed
      diagnosis of stomach cancer and the same number of controls selected from five
      hospitals in Belgrade. Both groups were matched by the sex, age and living place.
      McNemar's test was used for testing differences in exposure to the hypothetic
      factors. Based on the analysis of various food intake frequency it could be
      concluded that nutrition of patients with stomach cancer was, in comparison with
      the one taken by the control group, poorer in animal proteins, vegetables and
      citrus fruits, and rich in cereals processed in the form of various pastas and
      sweets, delicatessen, canned food as well as fruit rich in unsaturated fatty
      acids (nuts).

PMID- 8560849
TI  - [The inflammatory response syndrome].

PMID- 8560851
TI  - [Infectious erythema caused by parvovirus B19--2 case reports].

PMID- 8560850
TI  - [Biological, psychological and social aspects of aging--prevention and
      therapeutic methods].

PMID- 8560852
TI  - [Plasmacytoma as a diagnostic problem--case report].

PMID- 8560853
TI  - [Testimony of Dr. Rudolf Archibald Reiss on the use of explosive missiles and
      injuries in Serbian soldiers in the battles of Jadar and Cer].

PMID- 8560854
TI  - Brain PGD2 and PGE2 changes during posthaemorrhagic hypovolemia in rats.
AB  - This study examined the changes of prostaglandins (PGs) E2 and D2 in brain
      structures of conscious rats during one hour period following acute bleeding. The
      analyses were performed in brain structures which are important for
      cardiovascular homeostasis (medulla oblongata, hypothalamus) and these which are
      not directly involved in central homeostatic mechanisms but are selectively
      vulnerable to low-flow states (hippocampus, cortex). Haemorrhage was induced by
      gradual withdrawal of blood from the cannulated right femoral artery (18 ml/kg,
      LD30) during a 3-min interval. The brain prostanoid contents were measured by
      radioimmunoassays. The bleeding induced significant changes in brain prostanoid
      content which were expressed to the highest extent in medulla oblongata and
      hypothalamus. The time course of the alterations in PGD2 and PGE2 contents was
      different in m. oblongata and hypothalamus from that in cortex and hippocampus.
      It was observed that PGE2 and PGD2 levels rose significantly in brain structures
      which are important for cardiovascular homeostasis and that their alterations
      were less expressed with different time course in structures which are
      selectively vulnerable to ischemia. Therefore, the authors suppose that the
      prostanoid changes in m. oblongata and hypothalamus are induced by the activation
      of central homeostatic mechanisms rather than by cerebral ischemia produced by
      haemorrhagic hypotension.

PMID- 8560855
TI  - [Abdominal war injuries].
AB  - In the period of July 1, 1991-December 31, 1992, 4292 wounded were treated in the
      Military Medical Academy (MMA) in Belgrade. Out of 410 (9.6%) wounded with
      abdominal war injuries, 156 (38%) received the primary treatment in MMA and the
      remainder in other hospitals. One fifth of the wounded with abdominal injuries
      suffered combined injuries of more organs and 82.7% of the cases had multiple
      injuries of one organ or combined injury of two or more abdominal organs.
      Wounding caused by explosive devices prevailed (61.5%), and the most frequently
      injured organs were small intestine in 40% and colon in 30.7% of the cases.
      Reoperation due to complications was performed in 7% of the wounded primarily
      managed in MMA and 33.8% of there primarily managed in other hospitals. Total
      mortality due to the abdominal war injuries was 10.9%, while mortality in
      patients primarily managed in MMA amounted to 4.5% compared to 14.9% of those
      operated on in other hospitals.

PMID- 8560856
TI  - [Analysis of treatment of perforating ocular injuries during warfare in Bosnia
      Herzegovina].
AB  - The analysis of 210 patients with penetrating eye injuries was performed. The age
      of the majority of injured was 20-30 (40%). Most injuries were caused by
      explosive devices (80%). Entering wounds were found on the cornea in 66.19%, on
      the sclera in 21.42% and on the limbus in 12.38% of the cases. Traumatic cataract
      was found in 45.72%, hemophthalmus in 53.33%, detachment of the retina in 40%,
      intrabulbar foreign body in 51.42%, prolapse of the iris and uvea in 36.19%, and
      endophthalmitis and hypopyon in 11.42% of the cases. Visual acuity after the
      operation was more than 0.10 in 37.89% of the cases. The basic principles of the
      treatment of penetrating eye war injuries were discussed.

PMID- 8560857
TI  - [Photocoagulation in the prevention of retinal detachment in perforating injuries
      of the eye caused by warfare].
AB  - Main indications for application of photocoagulation in the prevention of retinal
      detachment in penetrating eye war injuries were presented. Photocoagulation was
      performed when intrabulbar foreign body was present, before its extraction and in
      the cases of traumatic ruptures of sectorial traumatic tractional retinal
      detachment. Modified photocoagulation by argon laser, with linked spots in two
      rows was used since it was shown to be clinically the most suitable.

PMID- 8560858
TI  - [Experience in the care of ophthalmologic patients under difficult war
      conditions].
AB  - In the period of June 15 1992-June 1 1993, 4230 ophthalmological (patients
      conscripts and civilians) were examined at 5 points of East Herzegovina theater
      of operations. Some problems in management (great length of the front, scattered
      settlements and medical facilities, insufficient equipment, poor training of
      general physicians) were pointed out and suggestions for their solution were
      given.

PMID- 8560859
TI  - [Implantation of artificial lenses in primary and secondary management of severe
      eye injuries in warfare].
AB  - The authors report their experience concerning intraocular implantation of
      artificial lenses during primary management of the eye war injuries as well as
      during secondary management, after shorter or longer period of consolidation, on
      16 eyes of the same number of patients. Primary intraocular implantation was
      performed on 5 eyes simultaneously with primary management of the injured eye,
      while secondary implantation was performed on 11 eyes later, after more or less
      time of consolidation of the primary wound treatment. In regard to anatomical and
      functional consequences of severe trauma of the eye and the surgery itself, the
      functional state of the eyes operated on was satisfactory. The most frequent
      chronic complications were deformities of the pupil and, to a lesser degree,
      secondary cataract.

PMID- 8560860
TI  - [Psychotraumatic reactions in participants and non-participants in warfare-
      members of a special unit].
AB  - The investigation was performed on a sample of members of a special parachute
      unit, aged 25-30 years. During combat activities in the territory of former
      Yugoslavia, in the period of 1991-92, they were exposed to intensive stress and
      psychotraumatic events which could have detrimental influence on personality and
      psychological functions, most frequently causing posttraumatic stress disorder.
      The results of investigation showed that in spite of numerous traumatic
      experiences, psychological stability and professional efficiency could be
      maintained in specially selected individuals with appropriate personality
      structure, who were particularly motivated and included in so-called elite units,
      which show high degree of group cohesion and mutual support. This investigation
      used for the first time the methodology, most frequently recommended in
      literature as standard for follow up and early diagnosis of psychological
      disorders caused by traumatic stress in war or everyday life. Practical value of
      the used methodology, which included the list of stress-inducing events, the
      scale of influence of stress-events and the interview for posttraumatic stress
      disorder, was confirmed.

PMID- 8560861
TI  - [Anticardiolipin antibodies in patients with ischemic brain disease].
AB  - Anticardiolipin antibodies are best defined antiphospholipid antibodies and a
      recently described marker of increased risk for ischemic brain disease.
      Investigations were performed in 151 patients with ischemic brain disease in
      order to determine the occurrence of anticardiolipin antibodies and define the
      clinical characteristics of patients with an increased titer of anticardiolipin
      antibodies. Measurement of anticardiolipin antibody titer was performed by
      immunoenzyme method. Besides, analyses of certain tests indicative for blood
      coagulative properties were also done. In addition, the occurrence of
      anticardiolipin antibodies was investigated in 49 patients with other non-immune
      neurological diseases and disorders. Control sera were obtained from 50 healthy
      subjects and 6 patients with senile cataract. Investigation showed the increase
      of anticardiolipin antibody titer in 22.8% of the patients with ischemic brain
      disease (30% with transient ischemic attacks, 19% with brain infarction) and in
      4% of the patients with other neurological disorders of non-immunological
      genesis. The patients with increased titer of anticardiolipin antibodies suffered
      more frequently from recurrent forms of ischemic brain disease, all of them were
      below 50, and they had less risk factors for atherosclerosis and ischemic brain
      disease. It was concluded that the presence of increased titer of anticardiolipin
      antibodies in younger patients with recurrent forms of ischemic brain disease and
      less risk factors could be the marker of the increased risk for ischemic brain
      disease.

PMID- 8560862
TI  - [Anatomic and clinical characteristics of arteriovenous malformations of the
      brain].
AB  - Vascularization, drainage and clinical presentation were analyzed on the series
      of 25 patients with cerebral arteriovenous malformations (AVM), diagnosed by
      pancephalic angiography. Monoarterial vascularization was most frequently seen in
      frontally localized anomalies, and drainage was always done by the nearest major
      venous vessel (dural sinus of Galen's vein). Initial symptom was intracranial
      bleeding in 60%, and epilepsy in 40%. Intraventricular bleeding occurred
      initially in all paraventricular AVMs. All focal attacks occurred in parietal
      AVMs, all psychomotor in temporal AVMs and 80% of generalized attacks occurred in
      cases of frontal anomalies. The most frequent symptom was headache (44%).

PMID- 8560863
TI  - [Prevention of Lyme disease].

PMID- 8560864
TI  - [Interactions between the immune and neuroendocrine system].

PMID- 8560865
TI  - [Development and use of expert systems in medicine].

PMID- 8560866
TI  - [Endophthalmitis caused by Fusarium moniliforme and Pseudomonas species].

PMID- 8560867
TI  - [Neuropsychiatric disorders in patients with cryoglobulinemia].

PMID- 8560868
TI  - [Paramyotonia congenita].

PMID- 8560869
TI  - [Development and problems of health services in the Royal Serbian and Royal
      Yugoslav Army according to the papers of General and Dr. Zarko M Ruvidic. I].

PMID- 8560870
TI  - [Study of immunomodulating properties of beta-carotene in patients].
AB  - It was shown that in patients with hypertension, duodenal and gastric ulcers and
      erosive gastritis leukopenia and lymphopenia are seen. At the same time contents
      of T- and B-lymphocytes are decreased and contents of C- lymphocytes are
      increased in circulation blood. Peroral daily intake of 20 mg of beta-carotene
      during 3-4 weeks caused increasing the contents of B- and T-cells and decreasing
      contents of C-lymphocytes in blood of patients.

PMID- 8560872
TI  - [Artificial therapeutic nutrition using special food mixtures in complex
      treatment of patients].
AB  - The experience of using special food mixtures for enteral nutrition in treatment
      of 5518 of the wounded and inpatients allows propose practical conception of
      using these artificial food mixtures at different pathological situations. The
      whole characteristics, nutritional and biological values of these mixtures and
      methodology of their applications are summarized.

PMID- 8560871
TI  - [Interrelationship between dietary intake of minerals and prevalence of
      hypertension].
AB  - 1556 of men living in Kiev aged 20-59 years were examined to evaluate
      interrelationship between the dietary intakes of Ca, Mg, P, Fe, Cu, Zn and level
      of arterial blood pressure (AP). Dietary intake was studied by 24-h recall
      methodology. Systolic AP > 160 mm Hg and/or diastolic AP > 90 mm Hg were referred
      as arterial hypertension (AH). It was shown that high dietary intakes of Ca or Zn
      were related with the higher rate of AH. At low level of dietary intake of Mg, Cu
      or P the prevalence of AH was seen in 1.8-2 times more often than at high level
      of intake of these micronutrients. Mean systolic AP had trend to increasing and
      diastolic AP was significant higher at low level of dietary intake of P.
      Correction of dietary intake of microelements should be used in preventive
      measures of AH.

PMID- 8560873
TI  - [Complex formation in manufacturing of infant foods].
AB  - Until now the questions related to the character of lipid-protein interaction,
      the nature and role of their complexes and compounds still remain in dispute. The
      subjects of this paper are the investigation of the character of lipid-protein
      interaction during technological treatment of baby food mixtures, the elucidation
      of technological conditions leading to the formation of such complexes and the
      optimization of the manufacturing conditions of final products.

PMID- 8560874
TI  - [Biomedical aspects of the use of milk whey in nutrition (review)].
AB  - The present review of biotechnological research-works is connected with the use
      of milk whey in nutrition. The review deals with the use of milk whey in
      nutrition. The review deals with those aspects of the problem which prevent the
      widest use of milk whey possible in this field. A detailed review of
      technological methods is given, as far as their role in increasing the
      nutritional and biological value of milk wheys is concerned. The review also
      contains new data about modern ways of milk whey processing and a brief
      evaluation of the final products.

PMID- 8560876
TI  - [Problems restraining development of infant foods manufacture].

PMID- 8560875
TI  - [The vitamin provision of the adult population of the Russian Federation and
      changes during 1983-1993. II. Vitamin B complex].
AB  - The present paper is a continuation of the previous communication ("Problems of
      Nutrition" No4/95). The paper contains the generalized analysis of the data
      obtained by the laboratory of vitamin and mineral metabolism of the Institute of
      Nutrition during investigation of vitamin B1, B2, B6, B12 and folic acid
      provision of adult able to work population (men and women) of different regions
      of Russian Federation (Moscow, Ekaterinburg, Orenburg, Kusnetzk Basin, West and
      East Siberia, Far East, Bashkyria, Mary-El) from 1983 till 1993.

PMID- 8560877
TI  - [Certification of food products].

PMID- 8560878
TI  - [Vitamin and health status of miners of the Karaganda coal basin].
AB  - Vitamin status, health statistics and capacity for work of miners of
      Karagandinsky coal field were studied. It was shown that inadequate vitamin
      nutrition of miners in combination with harmful occupational and environmental
      factors negatively influence the miner's health status and capacity for work.

PMID- 8560879
TI  - Age-specific incidence of cancer in Kingston and St. Andrew, Jamaica, 1988-1992.
AB  - During the period 1988-1992, a total of 4,030 malignant neoplasms were recorded
      in Kingston and St. Andrew, Jamaica. These comprised 1,829 in males and 2,201 in
      females. Histological confirmation was obtained in 83.4%. The crude incidence
      rate for males was 128.5, and 136.2 for females. The age-standardized rates (ASR)
      were 179.9 for males and 166.1 for females. Age-specific rates by site, sex and
      age are tabulated. Attention is drawn to increased incidence for cancers of
      prostate, larynx, bronchus and non-Hodgkin's lymphoma in males. There was also an
      increase in female breast cancer (crude rate 36.0; ASR 47.1). Invasive cervix
      cancer has shown no significant change in incidence. Neoplasms of the body of the
      uterus have increased (crude rate 7.6; ASR 9.5). The rise in cancer of breast and
      body of uterus suggests that the influence of exogenous oestrogens should be
      considered.

PMID- 8560880
TI  - Cutaneous furuncular myiasis in a Jamaican resident.
AB  - Data are presented on a case of cutaneous furuncular myiasis in a Jamaican
      resident. This condition is virtually unknown in the Caribbean, but is endemic in
      Central and South America. The infection, which was caused by Dermatobia hominis,
      was acquired in Belize and was misdiagnosed and treated as infected insect bites.
      Cutaneous furuncular myiasis should be considered in patients with sub-acute
      inflammatory nodular skin lesions with a history of recent travel to endemic
      countries.

PMID- 8560881
TI  - The class of 2000.

PMID- 8560882
TI  - Activation of guanylate cyclase in the guinea-pig trachea reduces contractile
      responses of the smooth muscle.
AB  - Guinea-pig tracheal strips were used to investigate whether activation of
      guanylate cyclase in the trachea can reduce the contractile responses of the
      smooth muscle. Guanylate cyclase was activated by glyceryl trinitrate and a
      combination of sodium nitrite and ascorbic acid. These activators inhibited
      tracheal smooth muscle contractions produced by acetylcholine, histamine and
      electrical field stimulation. However, in the presence of methylene blue, a
      guanylate cyclase inhibitor, tracheal smooth muscle contractions were not
      inhibited by the activators. But, in the presence of propranolol, which blocked
      inhibition mediated by beta-adrenoceptor, both glyceryl trinitrate and the sodium
      nitrite/ascorbic acid combination were still capable of inhibiting tracheal
      smooth muscle contractions. Additionally, methylene blue inhibited tracheal
      smooth muscle relaxation that was electrically induced. These results suggest
      that the inhibitory action mediated by activated guanylate cyclase may be a
      mechanism for regulating tracheal smooth muscle contractile responses.

PMID- 8560883
TI  - Pharmacoeconomics of intravenous antibiotic use in serious infection.
AB  - A pharmacoeconomic study of 15 antibiotics available in Barbados was performed.
      The antibiotics studied were amoxycillin/clavulanate, ampicillin,
      ampicillin/sulbactam, cefazolin, cefotaxime, ceftazidime, ceftriaxone,
      clindamycin, cloxacillin, cotrimoxazole, gentamicin, imipenem, metronidazole,
      piperacillin, piperacillin/tazobactam, and vancomycin. The costs of use of these
      compounds were calculated for a five-day course using a formula comprising eight
      categories: antibiotic purchase cost, maintenance of intravenous access, drug
      delivery cost, drug monitoring cost, dose readjustment, general monitoring cost,
      'sharps' disposal cost and adverse effects. The costs of adverse effects were not
      included in this study due to lack of accurate data. The total cost of antibiotic
      use (in U.S. dollars) ranged from $42.52 to $463.73 per five-day course. Generic
      compounds were less expensive ($45.52 - $98.23) than brand-name compounds
      ($106.18 - $106.18 - $463.73). Antibiotic purchase costs accounted for
      proportions of total costs ranging from 7 to 93%. Non-drug costs represented a
      much greater proportion of total costs of generic compounds. For most compounds
      the non-drug costs were related to the frequency of dosing, but for gentamicin
      the non-drug costs were relatively higher because of the need for monitoring of
      serum gentamicin levels. Efficacy and freedom from side-effects will remain the
      most important determinants in the choice of antibiotic therapy. However,
      pharmacoeconomic analyses can provide prescribers with the information required
      to make cost-effective choices for treatment of their patients.

PMID- 8560884
TI  - Idiopathic focal and segmental glomerulosclerosis in Jamaica. A 10-year review.
AB  - Idiopathic focal and segmental glomerulosclerosis (IFSGS) in a predominantly
      black population does not appear to behave any differently than in Caucasian
      patients. Response to steroid therapy and cyclophosphamide had favourable
      prognostic significance. There may be a subgroup of IFSGS which responds more
      slowly to steroids. The duration of steroid therapy should extend beyond four
      months.

PMID- 8560885
TI  - Childhood portal hypertension in Jamaica.
AB  - Portal hypertension and bleeding from oesophageal varices in children remain a
      difficult medical problem. The clinical course and management of children with
      portal hypertension seen over a 14-year period was reviewed. There were 5 females
      and 2 males with a mean age of 3.6 years at presentation. Five patients presented
      with severe upper gastrointestinal bleeding and two with severe hypersplenism.
      All patients had extra-hepatic portal hypertension. Five patients were treated
      with endoscopic sclerotherapy, including one who had bleeding five years post
      splenectomy. A mean of 9 sclerotherapy sessions was performed in each patient.
      Complete obliteration of varices was not achieved in any patient and a single
      rebleeding episode occurred in four. Three children underwent operative
      management consisting of splenectomy in two and splenectomy and central spleno
      renal shunt in one. There was no mortality in either group after a mean follow-up
      of 4.3 years. Sclerotherapy may not be totally successful in long-term management
      of childhood portal hypertension. Surgical therapy or a combination of
      sclerotherapy and surgery may be the best approach.

PMID- 8560886
TI  - Pre-operative autologous blood donations. A five-year experience in Trinidad and
      Tobago.
AB  - A pre-operative autologous blood donation programme was started in 1988 and made
      available to all doctors offering elective surgical procedures. Two hundred and
      seventy-seven (277) patients presented for autologous donation over a five-year
      period. Nine point four per cent were rejected because of low haemoglobin ( <
      10.5 g/dl). The single biggest user of the programme was the Princess Elizabeth
      Hospital for handicapped persons. Patients undergoing orthopaedic procedures gave
      50% of the donations, and ranged in age from 10 to 73 years. The oldest donor was
      a 73-year-old man who had an abdominal aortic aneurysm replaced. Gynaecological
      surgeons in the public and private sectors together provided 43.9% of donors,
      3.6% of these underwent elective Caesarean Section, each donating one unit of
      blood at 36 weeks. Patients undergoing general surgical procedures comprised
      10.4% of donors. Autologous donors contributed 1.3% of the total number of
      donations over this period.

PMID- 8560887
TI  - Primary aortoenteric fistula.
AB  - One hundred and thirty-eight patients with abdominal aortic aneurysms were
      treated by aneurysmorrhaphy over an eleven-year period. Six patients, all male
      and aged 60-74 years, were found to have developed primary aortoenteric fistulae.
      Four patients presented with bleeding into the gastrointestinal tract in
      association with a tender abdominal swelling. In the other two cases, the
      aneurysm was discovered at emergency laparotomy for gastrointestinal haemorrhage.
      The presence of the fistula was confirmed at operation in five patients and at
      autopsy in one. Two patients died, one from a massive gastrointestinal
      haemorrhage prior to surgery, the other from sepsis complicated by Adult
      Respiratory Distress Syndrome and renal failure following operation.

PMID- 8560888
TI  - Aetiology of vaginal infections in pregnant and non-pregnant women in Barbados.
AB  - The aetiology of vaginal discharge was studied in 175 Barbadian women. Pregnant
      women accounted for 52% (91) of the population studied. Candida albicans was
      detected in 45% of the women, bacterial vaginosis in 28% and Trichomonas
      vaginalis in 8.6%. Bacterial vaginosis was more common in non-pregnant women (33%
      vs 23%) whereas C. albicans was more common in pregnant women (49% vs 39). T.
      vaginalis was found with almost equal frequency in pregnant and non-pregnant
      women. Mixed infections were found in 10 women and an aetiological agent was
      detected in 75% of the women studied. These data emphasize the need for
      laboratory investigation of vaginal discharge since each of these infections can
      be treated effectively with specific agents.

PMID- 8560889
TI  - A pilot study of alcohol and drug-related traffic accidents and death in two
      Jamaican parishes, 1991.
AB  - This study is a preliminary effort to document the role of drugs in motor vehicle
      accidents as it examines the presence of alcohol, marijuana and cocaine in blood
      samples of thirty-one motor vehicle fatalities. The study identified that males
      (90.3%) and pedestrians (41.9%) were killed most often. Evidence of alcohol
      intake was found in 77.5% of the fatalities and 35.5% had alcohol levels above
      the legal acceptable limits. Traces of marijuana were found in 22.5% and a
      combination of alcohol and marijuana in 22.5% of the victims.

PMID- 8560890
TI  - [Percutaneous transhepatic cholangioscopy (PTCS)--evaluating the clinical
      status].
AB  - In 44 patients with biliary obstructions, percutaneous transhepatic
      cholangioscopy (PTCS) was performed during percutaneous transhepatic biliary
      drainage procedures (PTCD). In all patients the obstruction could be decompressed
      via the PTCD sufficiently. 30 of these cases who had PTCS showed suspect hepatic
      and pancreatic malignancies. In contrast to the brush cytology (14% false
      negative) the biopsies revealed insufficient histology in 33%. However, in 3
      cases a more extended tumor site was seen that at the initial exploration, shown
      by ERCP.

PMID- 8560891
TI  - [A new concept in imaging pelvic recurrence of curatively operated rectal
      carcinoma--image fusion of nuclear magnetic resonance tomography and anti-CEA
      immunoscintigraphy (SPECT): technique and clinical example].
AB  - We present a new technique of image fusion (IF) of magnetic resonance imaging
      (MRT) and anti-CEA-immunoscintigraphy (Behring 431/26) and single photon emission
      computed tomography (SPECT). We performed SPECT and MRT within 8 hours on the
      same day. Glucagon intravenously was used to reduce artefacts due to intestinal
      motility. Before image fusion we analysed the SPECT and MRT images independently
      of each other. The MRT and SPECT were connected by a local area network (LAN) to
      a Gateway computer, which is also used as a picture archive. There a program
      automatically starts, translates the MRT data from the ACR/NEMA format to the
      Elscint one and these data are sent for image fusion to the nuclear medicine
      computer Elscint SP1. By means of a clinical example we present anatomic
      concordant superimposition and explain the findings and the clinical value of our
      technique. This system and technique are equally applicable to other digital
      imaging investigations. By IF, on the basis of the certain evidence of the tracer
      depot of a pathological lesion diagnosed by MRT and the reliability of the
      anatomical assignment of a focal lesion diagnosed by SPECT, early detection of
      local recurrence after surgical treatment of rectal cancer, the correct
      localisation of recurrent disease and its distinction from non-malignant tissue
      becomes possible. This enables planning of further therapeutical strategies.

PMID- 8560892
TI  - [Total cavo-pulmonary connection as a therapeutic principle in anatomical and
      functional univentricular heart].
AB  - The original Fontan operation was employed for patients with tricuspid atresia,
      but its application has been extended to a broad spectrum of congenital cardiac
      defects with a functional or anatomical single ventricle. From 1989 to 1995, 35
      patients (23 males, 12 females) underwent a modified Fontan procedure; their age
      ranged from 14 months to 15 years (mean 5.1 a). Indications for operation were
      the following: D(S)ILV = 16, TA = 9, MA = 3, TGA with straddling AV-valve = 2,
      DORV = 4 and criss-cross heart = 1. The same surgical technique was utilized in
      all patients with redirection of the systemic venous return by means of a
      bidirectional cavopulmonary anastomosis and an intraatrial baffle, adaptable to
      all the various forms of underlying anatomy. Associated anomalies such as
      dextrocardia, coarctation, anomalous systemic or pulmonary venous return,
      subaortic stenosis and situs anomalies were present in 26%, 9%, 26%, 9%, and 20%,
      respectively. 12 patients were presumed to be at high risk and underwent a two
      stage procedure (n = 7 bidirectional Glenn preceding the definitive repair and n
      = 5 a fenestration of the intraatrial baffle). Risk factors in our group of
      patients were: age under 2 years, abnormal systemic venous drainage, stenotic
      pulmonary arteries, PVR over 2 Wood units, mPAP over 15 mmHg, AV-valve
      incompetence, subaortic obstruction and ventricular dysfunction. Two patients had
      failure of the total cavo-pulmonary connection necessitating the take-down to a
      bidirectional Glenn anastomosis in the early postoperative period, with one
      death. Hospital mortality was 24% (n = 8). One child did not survive
      complications following the fenestration closure 4 months
      postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8560893
TI  - CMV antigenemia (the lower matrix protein PP65), a marker for the guidance of
      antiviral therapy in cytomegalovirus disease after orthotopic heart
      transplantation.
AB  - During CMV viremia, the CMV specific lower matrix protein CMV pp65 can be
      detected in the nucleus of polymorphonuclear cells. A relationship has been found
      between the number of CMV pp65 positive cells, the clinical course and the effect
      of antiviral treatment on CMV disease. From 1990, heart recipients (triple drug
      therapy) were screened for CMV pp65 (antigenemia, according to the method
      described by The et al.), anti-CMV-IgM and -IgG. Tests were repeated at least
      every 4 weeks. Group 1 consisted of 23 patients who had been transplanted at
      least one year before the introduction of CMV testing as described. Between 1990
      and 1992 26 patients were followed up during the first year after transplantation
      and represent group 2. In group 1, 1184 antigenemia assays were performed and 13
      tested positive. In group 2 (1195 tests, 261 positive results), 20 out of the 26
      recipients tested positive for CMV pp65. Without preceding evidence of a positive
      CMV pp65, no rise of IgM or IgG antibodies was observed. The time until the first
      antigenemia (time from detection until a subsequent test remains negative); 13
      were found in group 1, 84 in group 2. In group 2, 46 episodes of antigenemia
      (mean duration 24.5 +/- 27.1 days) consisted of more than 1 consecutive positive
      result of the antigenemia assay (4.8 +/- 4.1). During these episodes the white
      blood cell count was 3460 +/- 1790/mm3. After the episodes, the mean leucocyte
      count was 6320 +/- 1870/mm3. The detection of CMV antigenemia indicated the
      initiation of antiviral treatment (hyperimmune globulin and ganciclovir). Therapy
      was stopped again when the antigenemia assay tested negative again. Antigenemia
      disappeared in all patients after initiation of antiviral treatment, CMV disease
      was not observed. CMV antigenemia mainly cumulates within the first year after
      heart transplantation. Antigenemia directed antiviral therapy does not prevent
      infection or repeated antigenemia but prevents CMV disease after heart
      transplantation.

PMID- 8560894
TI  - [Development of trauma surgery and the Graz trauma surgery university clinic].
AB  - The relatively late achievement of independence of the traumatological Department
      from the Department of Surgery at the University of Graz is described, as well as
      the development of the operative trauma school in Graz/Austria for the management
      of injuries. Despite the lack of staff, space and equipment international
      accepted contributions in research, teaching and specialized treatment of trauma
      patients have been established.

PMID- 8560895
TI  - [3-years results of endoprosthetic management of radiation-induced hip joint
      necrosis].
AB  - Radioosteonecrosis of the acetabulum is a rare side effect of radiotherapy. The
      latency period of 2 to 17 years is much longer than that reported for other bones
      (1-3 years). The reason for this is unknown. Plane radiograms show sclerosis,
      cysts and fractures of the acetabulum and, in most cases, a migration of the
      femoral head with flattening. The diagnosis of a radioosteonecrosis has to be
      made by exclusion of malignomas by scintigraphy and MRT or CT. This paper
      presents the follow-up of four patients treated by total hip replacement (THR)
      for radioosteonecrosis of the acetabulum. Within 9 months postoperatively the
      fractures of the acetabulum had healed with full weight bearing. 36 to 78 months
      after operation no signs of progression of the bone changes were detected. In
      this period the loosening of one spherical thread cup occurred, but a radiolucent
      gap above a cemented cup stayed unchanged. We conclude that irradiation damage of
      the acetabulum can be treated successfully by THR even in cases with fractures of
      the acetabulum as far as a stable implantation can be achieved and the remaining
      osteoblasts are preserved by the procedure.

PMID- 8560896
TI  - [Indications and results of ex-vivo surgery of the kidney].
AB  - 394 renal transplantations have been performed in our unit between 1974 and 1995.
      In all instances extra-corporal surgical procedures on the graft, its vessels
      and, in rare instances, on the collecting system were necessary. The surgical
      procedures, which took up to 90 minutes on the work-bench, ranged from repair of
      minor iatrogenic vascular injuries to major vascular reconstructions, in order to
      facilitate the subsequent implantation of the graft. During the same period work
      bench surgical procedures with subsequent autotransplantation were performed in 8
      patients. The indication for such a procedure was a renal cell carcinoma in 2
      patients with a solitary kidney and bilateral renal cell carcinoma in 1 patient,
      as well as renovascular disease (renal artery stenosis, aneurysm of the renal
      artery) in the remaining 5 cases.

PMID- 8560897
TI  - [Prenatal diagnosis of abnormalities of the urinary tract].
AB  - During the period January 1983 to December 1993 malformations of the urinary
      tract were suspected in 166 cases prenatally and confirmed after birth. Boys
      dominated (72% of cases); in 66% of the cases the malformation was unilateral.
      The most frequent diagnosis was ureteropelvic obstruction in 74 infants (45%). 73
      out of 166 infants (44%) required surgical intervention. Altogether 124
      operations were performed (68% temporary diversions; 32% definitive corrections).
      The high number of required interventions already during the first month of life
      highlights the importance of prenatal screening for the early detection of
      urinary tract malformations, especially obstructive uropathy and multicystic
      dysplastic kidney. On the other hand, vesicouretal reflux is usually detected
      only postnatally on investigation of a urinary tract infection.

PMID- 8560898
TI  - [Hyperbaric surgery and oxygen therapy in clostridial myonecrosis].
AB  - 116 patients with verified clostridial myonecrosis were treated by means of a
      regimen of combined cyclic hyperbaric oxygenation at 3 ata and repeated
      necrectomy. With proximal localization of gas gangrene in the elbow or knee (n =
      55) 34.5% of patients survived, whilst with peripheral localization at the limbs
      (n = 44) the survival rate was 88.6% amputation being avoided in 21 of these
      cases. Abdominal localization (n = 17) was associated with the lowest survival
      rate (23.5%). In spite of severe clostridial toxicity in 80.1% of patients at the
      time of admission, the overall mortality was 50.8%.

PMID- 8560899
TI  - [Plastic surgery in the tension field of surgery].
AB  - The 70th birthday of Professor Kraft-Kinz, who holds the Chair of Surgery at the
      University of Graz, is a suitable occasion to review the development of several
      surgical disciplines into independent specialist fields. Plastic surgery is one
      such monospecialty which has been in existence as a separate entity for the past
      7 years. Important personalities and events in surgery are traced back to the
      18th century and described from an Austrian perspective, with particular
      reference to the University of Graz. The process of achieving independence since
      1988, in conjunction with the application of new techniques, in particular
      microsurgery, has led to enormous expansion of this specialty, both regarding
      quantity and quality of practice. Hence, the initial divergence has changed to an
      overlapping convergence of the specialties and the current interdisciplinary
      cooperation is of great benefit to all the individual subspecialist fields. This
      is illustrated by means of case reports representing two distinct areas of
      exemplary interdisciplinary interaction in surgical management.

PMID- 8560900
TI  - [Epithelioid leiomyosarcoma of the stomach. Clinical experiences with a rare
      stomach tumor].
AB  - Gastric epithelioid leiomyosarcoma (epLMS), which generally occurs in mid- or
      late adult life, is a rare smooth muscle tumor of the stomach. Out of 25 soft
      tissue tumors of the stomach operated at the Department of Surgery, University of
      Graz, two epLMS were diagnosed. This paper presents the case of a 67-year-old
      male with an epLMS in the corpus and of a 80-year-old female with an epLMS in the
      fundus of the stomach. The tumors were not diagnosed by gastroscopy; they were
      localized by sonography and CT-scan. In both cases the tumor was completely
      removed surgically, using a TA 90 4.8 mm respectively a TA 55 4.8 mm stapler.
      Diagnosis was reached by histological and immunohistochemical examination of the
      tumor tissue. Surgical excision with wide tumor-free resection margins is the
      therapy of choice in this tumor group.

PMID- 8560901
TI  - [Effectiveness, tolerance and safety of simvastatin in comparison with
      bezafibrate in treatment of hypercholesterolemia].
AB  - The efficacy, tolerability and safety of simvastatin was compared to that of
      bezafibrate in a randomized placebo controlled double-blind trial including 64
      patients with primary hypercholesterolemia with total cholesterol levels above
      240 mg/dl and low-density lipoprotein (LDL) cholesterol above 195 mg/dl. During a
      placebo period of four weeks patients were counselled for a diet low in
      cholesterol (< 300 mg/day) and saturated fat (< 10% of calories). This period was
      also used for randomization of the individuals into the bezafibrate and
      simvastatin group, respectively. Patients assigned to bezafibrate treatment took
      bezafibrate at 600 mg/day throughout the entire 12 weeks of active treatment.
      Patients assigned to simvastatin took simvastatin at 10 mg/day when LDL
      cholesterol was below 195 mg/dl, and at 20 mg/day when LDL-cholesterol was above
      195 mg. To compare the lipid lowering effect of both substances total
      cholesterol, LDL- and high-density lipoprotein (HDL)-cholesterol were measured as
      well as triglycerides, very low density lipoprotein (VLDL)-cholesterol and the
      concentrations of apolipoproteins (apo)-AI, apo-AII and apo-B, respectively.
      These variables were compared between the two study groups with respect to the
      percentage change from baseline levels obtained during the placebo period. After
      a 12 week treatment period mean percent reduction of total cholesterol in the
      simvastatin group was 24% and that of LDL-cholesterol was 36%, both more
      pronounced than the respective reductions (14% and 17%) observed in the
      bezafibrate group. The mean percent increase in HDL-cholesterol was similar in
      both treatment groups (simvastation by 20% vs. bezafibrate by 17%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8560902
TI  - [Erectile dysfunction in patients with type I diabetes mellitus].
AB  - To improve diabetes care according to the St. Vincent Declaration an
      interdisciplinary working group on erectile dysfunction in patients with diabetes
      was installed in the Departments of Internal Medicine, Urology and Psychiatry at
      the University of Graz. The screening and basic diagnostic procedures are
      performed in the diabetes clinic in the Department for Internal Medicine. To
      inform the patients about the options of treatment of diabetic erectile
      dysfunction and to determine prevalence data an anonymous questionnaire with a
      pre-stamped envelope was sent to 133 male patients with diabetes mellitus type I
      (IDDM). 59 (44%) of the questionnaires were returned and could be analyzed. Mean
      age and diabetes duration were representative for the male diabetes population.
      The prevalence of erectile dysfunction in this group was 49%. 7% of the patients
      were completely impotent. None of the patients reported the use of erection aids
      as a vacuum device or intracavernosal injection of smooth muscle-relaxant drugs.
      The prevalence of erectile dysfunction is high among patients with diabetes
      mellitus type I. Modern management offers satisfactory success in most cases,
      therefore screening for erectile dysfunction and adequate therapy should be
      offered to all patients.

PMID- 8560903
TI  - [Electrocardiographic examinations after orthotopic heart transplantation].
AB  - The electrocardiographic examinations of 220 post orthotopic heart transplant
      patients have shown: A marked left axis deviation (LA hemiblock) was seen in
      15.9% of the patients and a marked right axis deviation in 6.8%. During the
      postoperative observation of the progress a change of the marked axis type became
      visible in 14.2% of the marked left axis type of the patients. 21.8% of the
      patients showed a pronounced (= complete) right bundle branch block pattern (QRS
      duration > or = 0.12 s), 90% of them a pronounced (= complete) bundle branch
      block pattern of the Wilson type. 15.9% of the patients showed a moderate (=
      incomplete) right bundle branch block pattern (QRS-duration > 0.1 < 0.12 s).
      Pronounced (= complete) or moderate (= incomplete) right bundle branch block
      pattern was noticed in 71.7% of the patients during the first 14 days
      postoperative. In 96.6% of the patients the right bundle branch block pattern
      remained constant. A progress course could be observed very rarely. A right
      ventricular dysfunction is a possible cause.

PMID- 8560904
TI  - [Sedation without risk of addiction--the melperon alternative].
AB  - In two thirds the medication of melperon in a geriatric sample yielded good (and
      often very good) results. The most important item in evaluation process was
      psychomotor restlessness. We tried to apply a new approach: nurses had the task
      to score the patients.

PMID- 8560905
TI  - Who will pay for our future?

PMID- 8560907
TI  - Patient satisfaction with current impotence therapy.
AB  - One hundred ninety-eight impotent men were evaluated between July 1993 and June
      1994. A "patient goal-directed" approach was used in all cases. Treatment options
      presented to patients included: oral yohimbine, vacuum constriction devices,
      penile self-injection therapy, penile prostheses, and testosterone
      supplementation when clinically indicated. Thirty-two percent of patients
      declined treatment, and 67% chose nonsurgical therapy. Only two patients (1%)
      chose penile prostheses. In August 1994, a survey addressing satisfaction with
      therapy was mailed to all patients, and 99 men (50%) responded. Of the treated
      respondents, 80% stated that their therapy was "easy to use," and 70% reported
      that they were "able to have intercourse." Patients prefer nonsurgical impotence
      therapy, which restores satisfactory sexual function in most men.

PMID- 8560906
TI  - Percutaneous balloon aortic valvuloplasty in high-risk elderly patients.
AB  - From 1987 to mid-1994 we performed 16 percutaneous balloon aortic
      valvuloplasties. All patients (mean age 80 years; 53% female, 47% male) had
      significant congestive heart failure from aortic valve stenosis; the majority
      were categorized as New York Heart Association Class IV (shortness of breath at
      rest). Twelve patients were not surgical candidates; four patients refused
      surgery. After valvuloplasty, all patients became asymptomatic (NYHA Class I &
      II), the average preprocedure valvular gradient of 59 mm Hg decreased to 31 mm
      Hg, and valve area increased from 0.8 cm2 (0.3 cm2-0.98 cm2) to 1.3 cm2 (0.6 cm2
      1.44 cm2). The only complications were two minor groin hematomas (2 patients).
      Within 6 months, 50% of the patients were symptomatic again; the overall survival
      rate was 23 months. We conclude that in the proper environment this procedure can
      be effective and safe--even in high-risk elderly patients. Although symptom
      improvement is transient, valvuloplasty provides a valuable opportunity to treat
      intercurrent medical conditions and possibly follow up with surgery.

PMID- 8560908
TI  - A reason to hope: linking dementia research, care and services in the 21st
      century.

PMID- 8560909
TI  - Breast cancer mortality rates decline for Wisconsin women.

PMID- 8560910
TI  - The Wisconsin Women's Cancer Control Program: 1993-1995.

PMID- 8560911
TI  - Establishing a Women's Cancer Control Program using a multi-county consortium.

PMID- 8560912
TI  - A bold survivor: Wisconsin's first lady leads way to increasing breast cancer
      awareness.

PMID- 8560913
TI  - Video, support group are partners in survival.

PMID- 8560914
TI  - Medicare update: SMS summarizes proposed 1996 changes to Medicare Part B.

PMID- 8560915
TI  - Decreasing the rate of bilateral cardiac catheterization.

PMID- 8560916
TI  - Call to the community. II: We called; you responded.

PMID- 8560917
TI  - Public health strategies. To reduce firearm injuries and deaths in Milwaukee
      County. Executive summary.

PMID- 8560918
TI  - [The role of the catecholaminergic innervation of the neocortical frontal area in
      regulating the behavior of rats with differing resistance to acoustic stress].
AB  - Influence of 6-OHDA (40 mcg) injection in the frontal neocortex on behaviour was
      studied in Wistar rats with different resistance to sound-induced stress.
      Reduction of exploratory activity in the open field, reactivity to stimuli of
      different modality and deterioration of food-procuring conditioning were observed
      after 6-OHDA treatment of stress-resistant rats. On the contrary, treatment of
      non-resistant rats with 6-OHDA increased the reactivity to stimuli of different
      modality and the learning capacity. Thus, catecholaminergic system of the frontal
      neocortex is differently involved in the regulation of cognitive processes in
      stress-resistant and non-resistant rats.

PMID- 8560919
TI  - [The stress-protective effect of fenazepam in rats with different capacities for
      escape in an acute aversive situation].
AB  - Stress-protective effect of phenazepam (1 mg/kg) was studied in rats with
      different ability to avoid acute aversive situation. Two types of extreme
      situations were created, immobilization and hyperkinesia (permanent running
      inside the wheel). It was found out that rats which easily avoided acute aversive
      situation (I group) were more resistant to extreme effects. In immobilization
      stress phenazepam produced protective effect mostly in rats with low ability to
      avoid acute stress situation (II group). In situation with hyperkinesia the drug
      did not essentially influence the state of rats of the II group and even
      aggravated the state of rats of the I group. It seems likely that stress
      resistance of animals and dissimilar protective effects of phenazepam are
      determined by distinctions in coping mechanisms.

PMID- 8560920
TI  - [Damage to the catecholaminergic system causes a slowing in the formation of
      early behavioral reactions in rats].
AB  - Influence of 6-hydroxydopamine (6-OHDA) on catecholaminergic brain system and
      development of early behavioural patterns was studied in 1-20-days-old Wistar
      rats. After 6-OHDA neonatal injection the number on catecholaminergic terminals
      in deep layers of pons-medulla was considerably reduced while the number of
      catecholaminergic neurons was 2-3 times increased. Damage of catecholaminergic
      innervation of the forebrain of rats was shown to cause a delay in development of
      washing behaviour, searching activity and disturbance of orientation in new
      environment.

PMID- 8560921
TI  - [The alteration of a motor habit in rats with different motor preferences].
AB  - 60 mixed-bred male white rats were trained to reach food in a horizontal tube
      with a forepaw. In the second test access to the tube was limited by a partition
      so that the left-handed rats were forced to use the right forepaw and the right
      handed animals the left one. While the right-handed rats successfully changed for
      the unpreferred left limb the left-handed animals had problems in using the right
      forepaw. They were manifested in 1) longer time which it took for beginning
      manipulation with the unpreferred limb; 2) lower rate of manipulation; 3) smaller
      number of animals which succeeded in switching to the unpreferred limb; 4) higher
      number of attempts to use the preferred limb in the left-handed rats as compared
      with the right-handed ones. The authors suppose that distinctions in ability of
      rats to shift manipulatory reaction to the unpreferred forepaw result from
      different lability of inhibitory processes in the left and right hemispheres. In
      other words, ability of the right hemisphere to inhibit the program of
      manipulation with the dominant left paw (left-handed rats) is lower than that of
      the left hemisphere to inhibit the movement of the right forelimb (right-handed
      rats).

PMID- 8560922
TI  - [Sex differences in information processing in younger schoolchildren with
      different lateral profiles].

PMID- 8560923
TI  - [The influence of naloxone on the antinociceptive effects of stimulation of the
      emotiogenic brain structures].

PMID- 8560924
TI  - [The dynamic changes in dental and visual evoked potentials under conditions of
      immobilization and drinking stress].

PMID- 8560925
TI  - [A delay in the development of auditory sensitivity in nestlings and the
      reorganization of their feeding behavior].

PMID- 8560926
TI  - [A method for the multiple implantation of semimicroelectrodes into the brain of
      small animals for research in free behavior].

PMID- 8560927
TI  - [Diazepam eliminates the anxious state induced by amputation of the vibrissae (a
      model for assessing anxious behavior)].
AB  - Diazepam (0.5 mg/kg) prevented reduction of motor activity of rats (both vertical
      and horizontal components) induced by vibrissae amputation. It is suggested that
      the observed decrease in motility is related to development of a pathologic
      reaction of anxiety. The method is recommended as a test for anxious behaviour in
      experiment.

PMID- 8560928
TI  - [I. P. Pavlov on religion].

PMID- 8560929
TI  - [The dynamics of the high-frequency components of the brain electrical activity
      in dogs during cognitive activities].
AB  - Dynamics of parameters of low-voltage high-frequency components (HFC; 40 Hz and
      higher) of electrical activity (EA) of the brain in a broad frequency range (1
      256 Hz) was studied in dogs in the process of conditioning using correlation and
      spectral analysis. Motor skill of pressing the pedal of the food dispenser in
      response to presentation of sound stimuli was elaborated. Spectra of power,
      coherence and phase of EA were studied in interstimulus intervals (2-3 minutes)
      and intervals (1 sec) of EEG reaction to conditioned stimuli preceding the motor
      response. It follows from the distinctions between the parameters of EA at these
      states that underlying them mechanisms are different. It is assumed that the
      dynamics of HFC (40-170 Hz) in interstimulus intervals (intensification of HFC
      and dominance of small phase shifts) is an expression of cognitive activity
      (forming of the internal integral image of forthcoming activity). Characteristics
      of EEG reactions to the conditioned stimuli (increase of phase shifts between
      potentials) are regarded as a "motor program" which ensure direct realization of
      multicomponent motor reaction.

PMID- 8560930
TI  - [The regulation of the septal pacemaker of theta rhythm by the midbrain raphe
      nuclei].
AB  - Neuronal activity of the medial septum (MS--DB) and hippocampal slow
      electroencephalogram (EEG) were recorded in unanaesthetized rabbits with
      stimulating electrodes implanted in the median raphe nucleus and reticular
      formation of midbrain and pons. In all the animals with raphe electrodes the
      background frequency of theta-rhythm was decreased (mean 4.7 +/- 0.15 Hz) in
      comparison with the intact animals and those with stimulating electrodes in the
      reticular formation only (5.2 +/- 0.19 Hz, p < < 0.5). Stimulation of the raphe
      had effects of suppression of theta-bursts, decrease in their frequency and
      regularity, and appearance or increase of delta-modulation in MS--DB neuronal
      activity. The number of spikes per burst was decreased while interburst pauses
      became significantly longer. At the same time, gradual decrease of theta
      frequency and amplitude, theta suppression, appearance of irregular delta-waves
      and spindles were observed in the hippocampal EEG. Stimulation of the reticular
      formation evoked the opposite effects in MS--DB neuronal activity, as well as in
      the hippocampal EEG. The data confirm the role of the midbrain raphe in
      constraining the reticulo-septohippocampal system of theta-rhythm generation and
      do not support the statements on the existence of septum-independent high
      frequency serotonergic theta-rhythm. It is suggested that theta-limiting raphe
      influences may be important for suppression and switching of attention.

PMID- 8560931
TI  - [The lateralization of human visual-spatial perception during verbal
      reinforcement].
AB  - Influence of positive (word "good") and negative (word "mistake") verbal
      reinforcement on the ability of mental construction of six geometric figures from
      two fragments administered tachistoscopically under backward masking conditions
      was studied in healthy persons and patients with chronic alcoholism. In healthy
      persons negative verbal reinforcement induced a reduction in the latency of N200
      and growth of the amplitude of N200-P300 components of evoked potentials mainly
      in the right parietal area and vertex. There were no such changes in patients.
      Worse performance of the visuo-spatial task by the patients may be explained by
      the general suppression of the brain evoked potentials and disappearance of
      interhemispheric asymmetry which is characteristic for healthy persons and play
      an important role in visuo-spatial perception.

PMID- 8560932
TI  - [The effect of unconscious interoceptive afferentation on the spatial
      organization of the electrical activity in the human cerebral cortex].
AB  - The model of human perception and cortical regulation of unconscious
      interoceptive signals from the internal organs (heart, lungs, liver, intestines)
      was created by acupuncture of the corresponding channels. The features of the
      spatial organization of cortical electrical activity were analysed. A positive
      effect (for example, a decline of initially high heart rate) was accompanied by a
      fall in the general level of spatial synchronization, a decrease in the linear
      and non-linear correlations between potentials led from the anterior areas of the
      right hemisphere and the left posterior areas, and a growth of coherence in the
      range of 21.5-23 Hz. Absence of the acupuncture effect (or its negative
      influence) correlated with less expressed (or of another character) changes in
      the spatial organization of electrical activity. The conclusion is drawn that
      reorganization of cortical activity is necessary for perception and regulation of
      unconscious interoceptive information. Functional significance of this
      reorganization consists in the restriction of processing of exteroceptive
      information.

PMID- 8560933
TI  - [The effect of the brain stem structures on the shaping of the functional state
      of the human cerebral hemispheres (data from complex clinico
      electroencephalographic and neuropsychological research)].
AB  - To study the influence of the brainstem on formation of the functional state of
      the left and right brain hemispheres clinical electrophysiological examination of
      13 patients with focal brainstem lesions (neurinoma of the auditory nerve) was
      carried out before and after surgery. The result were compared with
      neuropsychological data. Definite correlation was revealed between the changes in
      coherent structure of EEG and neuropsychological estimation of the functional
      state of brain areas. The brainstem was shown to be more intimately functionally
      connected with the left hemisphere than with the right one. The regional
      specificity within the left hemisphere was determined by the form of cerebral
      decompensation.

PMID- 8560934
TI  - [The EEG characteristics in a lesion of different sections of the human caudate
      nucleus].
AB  - The study was aimed to reveal the characteristic features of EEG in 343 patients
      with caudate lesions depending on the localization of the pathological process
      (arteriovenous malformation, AVM). Methods of multivariate statistics were
      applied. It was shown that lesions in the body of the caudate nucleus (NC) were
      accompanied by the alpha-rhythm suppression up to its complete disappearance at
      the side of AVM and at the opposite side. Lesions in the head of NC were
      characterized by diffuse cortex irritation and local changes of the irritative
      character in the fronto-posterior and central regions at the side of AVM. Applied
      methods of EEG analysis made it possible to separate the influence of AVM
      localization within the limits of NC from other pathological factors accompanying
      it and to show the role of different parts of NC in formation of brain
      bioelectrical activity.

PMID- 8560935
TI  - [The characteristics of the spatial-temporal organization of the cortical
      potentials in the free-moving rabbit during training (a comparison of the stages
      in the generalization and specialization of the conditioned-reflex response)].
AB  - Analysis of successive topograms was applied to investigation of peculiarities of
      the spatio-temporal organization of cortical potentials of a rabbit at different
      stages of conditioning. Qualitative distinctions were shown between the stages in
      the character of regulation of the spatial synchronization (SS) related to
      variations in cortico-subcortical relations. Higher SS level at the stage of
      generalization changed for more complicated pattern of the spatio-temporal
      organization of cortical potentials. These complex spatio-temporal
      characteristics favoured facilitation of excitation spreading along the paths
      which provide specialization of the conditioned response under the action of the
      conditioned stimulus. Obtained results were correlated to specific membrane and
      synaptic modifications in the course of conditioning. The findings extend the
      notions of the cellular mechanisms which determine the features of the cortical
      SS at the stages of generalization and specialization of the conditioned reflex.

PMID- 8560936
TI  - [The dependence of striatal control over the temporal organization of behavior on
      the function of beta-adrenergic mechanisms].
AB  - Bilateral striatectomy disorganized the rhythmical structure of forced swimming
      and circadian motility of rats. Destruction of dorsal but not ventral striatum
      eliminated the effect of beta-adrenoblocker propranolol on temporal organization
      of behaviour. The results suggest that just the dorsal striatum is mainly
      subjected to adrenergic control.

PMID- 8560938
TI  - [Interstrain differences in extrapolation capacity and exploration of a cruciform
      maze correlate with various indices of monoamine metabolism in the brain].
AB  - C57BL/6J (B6) and CBA mice with normal karyotype and respective substrains
      carrying robertsonian translocation (fusion) of chromosomes 8 and 17 (Rb) were
      compared in their ability to extrapolate the direction of stimulus movement
      disappearing from the field of vision, rearings and hole-poke responses, and
      exploration strategies in a plus-maze. Rb mice were shown to be superior to
      normal karyotype groups in extrapolation behaviour. The pattern of interstrain
      differences in noradrenaline level in the cortex and serotonin turnover indices
      in the hippocampus correlated with differences in extrapolation ability, while
      exploration strategies in the plus-maze correlated with differences in dopamine
      level and its turnover rate in the neocortex and striatum. The data demonstrated
      that chromosomal rearrangement inducing behavioural differences was accompanied
      also by discrete neurochemical changes, and that spatial exploration strategies
      (being probably the constituent of general spatial abilities of mice) were to a
      large extent independent from extrapolation ability which was regarded as the
      index of animal reasoning capacity.

PMID- 8560937
TI  - [The correlation of dopamin- and enkephalinergic influences on rat conditioned
      reflex activity].
AB  - Behavioural effects of enkephalin microinjections into substantia nigra of rat
      brain were studied in short time after intrastriatal administration of 6
      hydroxydopamine (6-OHDA). It was shown that such microinjections improved
      conditioned activity of animals. A conclusion was made that the role of
      enkephalinergic brain structures in compensatory processes in acute period of
      development of 6-OHDA neurotoxic action was related to increase in efficiency of
      the mechanisms of self-regulation of dopamine neurons.

PMID- 8560939
TI  - [The relationship between catecholamine levels, tyrosine hydroxylase activity in
      the brain and the rank of male mice in a population hierarchy].
AB  - This study was aimed to investigate processes of biosynthesis in
      catecholaminergic system of male mice with genotypically determined dominant and
      submissive behaviour in population and their F1 offsprings. F1 inherited not only
      high capacity for dominance but also high tyrosine hydroxylase activity and
      catecholamine levels in striatum and hindbrain. It has been concluded that the
      high level of biosynthesis in catecholaminergic neurons is necessary for
      coordination of neurochemical systems involved in the regulation of genotypically
      determined dominant behaviour in male mice.

PMID- 8560940
TI  - [Long-term changes in the efficiency of the excitatory and inhibitory connections
      in the neuronal micronetworks of the motor cortex induced by tetanization of the
      thalamic nuclei and the sensory cortex].
AB  - Assumption was verified that tetanization which produces long-term potentiation
      (LTP) and long-term depression (LTD) in the efficacy of thalamo-cortical inputs
      and the inputs from the sensory cortex to motor cortex results also in long-term
      modifications of the efficacy of interneuronal interactions in the motor-cortical
      networks. It was shown that monosynaptic excitation of one of the neighbouring
      neurons in the motor cortex by rhythmical stimulation of some thalamic nuclei or
      the sensory cortex resulted in LTP or LTD in the efficacy of excitatory and
      inhibitory transmission between the neurons of the network. The efficacy of the
      synapses formed by the terminals of one axon on the neighbouring cells could be
      variously modified. If the network contained the neurons with multiple convergent
      inputs the tetanization resulted in the LTP of most of them. In the neuronal
      networks which contained local feed-forward inhibitory circuits, LTP (LTD) of the
      inhibitory input to the target cell was accompanied by LTD (LTP) of the
      excitatory input to the same target cell. Different patterns of modified
      interneuronal connections were caused by tetanization of different brain
      structures (thalamic nuclei or sensory cortex).

PMID- 8560941
TI  - [The restructuring of the neuronal activity of the lateral hypothalamic preoptic
      area during the development of sleep].
AB  - Activity of neurons of hypothalamic lateral preoptic area was studied in cats
      during wakefulness, drowsiness and slow-wave sleep. It was shown that development
      of sleep was accompanied by changes either in frequency and pattern or only in
      frequency of pulse activity. Neurons which increased their firing rate retained
      their initial activity pattern characteristic for wakefulness (continuously
      arrhythmic or burst firing) throughout all sleep stages. The majority of neurons
      which decreased their firing frequency changed their pattern of activity during
      drowsiness or SWS. Continuously arrhythmic activity changed for a mixed-type
      (combination of single-pulse and burst discharges), and mixed-type activity
      changed for bursting. During SWS substantial part of neurons displayed changes in
      activity which were phased-locked with sleep spindles. The results support the
      existence of somnogenic neuronal populations in the preoptic area which
      participate in the central mechanisms of transition from wakefulness to sleep and
      formation of the slow-wave phase.

PMID- 8560942
TI  - [The discrimination by the rabbit of light intensities and the plotting of its
      achromatic space].
AB  - Elaboration of differential instrumental conditioned reflexes in rabbits showed
      that probabilities of responses to differential stimuli were inversely related to
      differences in intensity between conditioned and differential stimuli. Factor
      analysis of a response probability matrix revealed two orthogonal axes. They
      could be interpreted as the axes of brightness and darkness in achromatic space
      of a rabbit. Lights of different intensities were located on a semicircle in
      accordance with their intensities. The experiments imply that light intensities
      are coded by excitation vectors composed of responses of brightness and darkness
      neurons.

PMID- 8560943
TI  - [The perceptive brightness space in the carp (Carpio cyprinus L.)].
AB  - Brightness discrimination of black-white (in the range of 0.0082-0.214 W/m2; CIE
      chromaticity coordinates X = 0.340, Y = 0.354) and red (in the range of 0.0035
      0.106 W/m2; CIE chromaticity coordinates X = 0.641, Y = 0.342) stimuli was
      studied during using choice conditioning paradigm in two carps. Confusion
      matrices for black-white and red stimuli separately were constructed from
      probabilities of instrumental responses (catching of a bead) to conditioned and
      differential stimuli in sequential six series in which one of ten intensities
      used in the experiment served as a conditioned stimulus. Confusion matrices were
      transformed into correlation matrices between the vectors which corresponded to
      the applied stimuli. Principal component analysis revealed two-dimensional
      circular structure of carp's brightness perceptual space both for achromatic and
      for red stimuli. This space was principally similar to that in humans. Two
      eigenvectors which constitute two-dimensional Euclidean space of brightness may
      be interpreted as bright and dark neuronal channels.

PMID- 8560944
TI  - [The characteristics of the effects of morphine and naloxone in rat strains
      differing by the excitability thresholds of their nervous systems].
AB  - Effect of morphine and naloxone on nociceptive sensitivity were studied in 3 rat
      strains, with high, low, and intermediate thresholds of nervous system
      excitability. The highest sensitivity to morphine correlated with its dose
      dependence was revealed in rats with low and high thresholds of excitability. The
      lowest sensitivity was found in rats with intermediate thresholds of
      excitability. The obtained data led to the conclusion about essential
      contribution of genetical control of excitability in the mechanisms of
      functioning of the opiate system.

PMID- 8560945
TI  - [Changes in the content of substance P, beta-endorphin and corticosterone in the
      hypothalamus and blood of rats with emotional stress after the administration of
      the delta sleep-inducing peptide].
AB  - The aim of this study was to investigate time-related changes in substance P (SP)
      beta-endorphin (BE), and corticosteron (CORT) levels induced by DSIP
      administration in rats subjected to emotional stress. Experiments were carried
      out in male Wistar and August rats with different resistance to emotional stress.
      At night rats were tied by their tails to the backside of the special cages.
      These stress-inducing procedure was repeated for 12 hours daily in the course of
      5 days. SP and BE immunoreactivity in the hypothalamus and plasma and blood CORT
      level were determined radioimmunologically. Six groups of animals were formed: 1.
      control animals; 2. stressed animals; 3. rats which received DSIP in a dose of 60
      nmol/kg one hour before decapitation; 3. rats to which DSIP was injected 24 hours
      before decapitation; 5. stressed rats to which DSIP was injected one hour before
      decapitation during the 5th exposure to stress; 6. stressed rats to which DSIP
      was injected 12 hours before the 5th exposure to stress, i.e. 24 hours before
      decapitation. Our experiments showed that DSIP administration induced marked
      changes in SP, BE, and CORT levels in the hypothalamus and blood plasma. This
      suggests that long-term stress-coping effects of DSIP in underlied by
      considerable changes in the content of other oligopeptides and hormones.
      Evidently, DSIP triggers these processes inducing a cascade of interrelated
      molecular reactions which are different in Wistar and August rats. It seems
      likely that DSIP administration stimulates the mechanisms of resistance in August
      rats to a lesser extent than in Wistar rats.

PMID- 8560946
TI  - [The neurochemical characteristics of rats differing by their behavior in the
      emotional resonance test. Free-radical processes and lipids of the cerebral
      cortex in older rats].
AB  - Free radical processes and lipid content in brain membranes were investigated in
      old male Wistar rats with differences in individual behaviour in "emotional
      resonance" test. Two groups of rats were selected, i.e. 1--which stayed for more
      than 2/3 of the total test time in the dark part of the experimental chamber and
      2--which spent the total test time in the light part of the chamber. Free radical
      processes and lipid content in the cortex of the left and right brain hemispheres
      did not differ in control animals of groups 1 and 2. Acute immobilization stress
      induced changes of the studied parameters depending on behavioural type. Rats of
      group 2 were more reactive than those of group 1.

PMID- 8560947
TI  - [The neurochemical characteristics of rats differing by their behavior in the
      emotional resonance test. Adenosine cyclic monophosphate in the brain structures
      of rats].
AB  - Content of cAMP in the frontal cortex (FC), hippocampus (HP), hypothalamus (HT)
      and amygdala (A) was determined in 20-month old male Wistar rats with different
      types of behaviour in "emotional resonance" test. Two groups of rats were
      selected, i.e., 1--animals which did not demonstrate ER phenomenon and 2--those
      which did not leave the light part of the chamber. Hippocampal content of cAMP
      was higher in group 1 than in group 2, in other brain structures no differences
      were detected. After acute immobilization stress cAMP level increased in FC, HT
      and A in both groups of animals. When the structures from the left and right
      hemispheres were analysed separately significant changes were revealed only in
      group 2 rats. Cross-correlations of cAMP levels between symmetrical FC, HP, HT
      and A were revealed in control animals of both groups. A number of new intra- and
      interhemispheric correlations appeared after stress, their pattern being
      dependent on behavioural type.

PMID- 8560948
TI  - [Inpatient-ambulatory psychoanalytic group therapy, a useful concept].
AB  - Concepts of group psychotherapy are standard in contemporary inpatient
      psychotherapy. The effective treatment combination of both inpatient and
      outpatient group psychotherapy, however, is less common. The following discussion
      evaluates the effectiveness of inpatient-outpatient group psychotherapy as a
      therapeutic method as well as its applicability for standard treatment.

PMID- 8560949
TI  - [Bio-psychosocial interactions in follow-up of Crohn disease].
AB  - The bio-psycho-social model serves as a guideline to the presentation of the main
      results of a longitudinal study of Crohn's disease (Heidelberg research project
      on Crohn's disease). The interactions and interrelations of the biological,
      psychological and social dimension during a 3 years' course of the disease are
      presented; in addition, the psychological data based on different theoretical
      concepts are compared to and linked with each other (defense/coping; disease
      concepts/personality and coping). Conclusions are drawn in respect to the
      biopsychosocial research on Crohn's disease and, more generally, to bio-psycho
      social research designs and research methodology.

PMID- 8560950
TI  - [Eating disorders and diabetes mellitus].
AB  - Numerous empirical studies indicate a higher frequency of eating disorders such
      as anorexia or bulimia nervosa in young female diabetic patients compared to the
      normal population. The comorbidity of the two syndromes usually leads to a
      continuous metabolic disorder bearing high risks of acute metabolic failure or
      early microangiopathic lesions. In addition to "restraint eating" as an essential
      element of diabetic therapy a premorbid neurotic malformation and/or poor coping
      strategies are further predisposing aspects for the development of an eating
      disorder. The inpatient treatment of a 22 year old patient suffering from both
      diabetes mellitus and bulimia nervosa demonstrates the association of neurotic
      malformation, poor coping style and the directive function of diabetic therapy.

PMID- 8560951
TI  - [2 sets of monozygotic twins concordant for anorexia nervosa].
AB  - The case reports at hand describe the discordant and the common characteristics
      of two pairs of monozygotic twins, concordant for anorexia nervosa. The resulting
      test scores of psychometric questionnaires including the Eating Attitudes Test
      (EAT) and the Eating Disorders Inventory (EDI) are descriptively presented and
      compared with each other. Finally the psychodynamic and the psychogenetic
      implications considering biogenetic findings are discussed.

PMID- 8560952
TI  - [Causal attributions and coping with illness by breast cancer patients: results
      of a longitudinal study].
AB  - The present 3-year longitudinal study investigated the relationship between
      causal attribution and coping mechanism. Data were collected in a group of 66
      breast cancer patients by self-report questionnaires. Three issues were
      addressed: 1. How do the patients explain the cause of their illness? 2. Do the
      subjective causes change over the course of three years? 3. What kind of
      relationship can be found between the causal attributions and the coping
      mechanism of the patients? Results showed a predominance of psychological
      attribution. Only little statistical prove could be found for changes between the
      four ratings. Analysing the individual data of the patients however revealed
      changing perceptions for about half the patients. A relationship between
      psychological attribution and depressive coping and problem solving as well were
      found.

PMID- 8560953
TI  - [Trauma of illness--crises in self concept regulation by cancer patients].
AB  - Oncological diseases often represent a psychic trauma, which leads affected
      patients into a narcissistic crisis. Starting from the concept of narcissistic
      regulation system (Deneke, 1989), the origins of the destabilisation of the self
      are described, and parallels to persecution trauma will be drawn. The longing of
      the patients for symbiotic relationships are investigated in their double sense.
      On the one hand they serve the patient to stabilise his self, on the other hand
      they involve the danger of traumatisation within an object relation. The
      consequences for the process of mourning and integration will be discussed.

PMID- 8560954
TI  - Temporal and spatial factors in diethylstilbestrol-induced squamous metaplasia in
      the developing human prostate. II. Persistent changes after removal of
      diethylstilbestrol.
AB  - To determine if the metaplastic effects of diethylstilbestrol (DES) on prostatic
      development are reversible, human fetal prostates (obtained from abortus
      specimens 6-22 weeks old) were bisected mid-sagittally; one half was grafted
      under the renal capsule of untreated, athymic, male nude mice and the
      contralateral half was similarly grafted into DES-treated hosts. Severe squamous
      metaplasia seen in the prostatic ducts after 1 month of continuous DES exposure
      either disappeared entirely or became reduced in extent and degree after
      retransplantation of the DES-treated specimens to untreated, intact male hosts
      and 2 additional months of growth. However, 14 of 21 DES-treated prostates
      harvested after a 2-month recovery period without DES revealed ductal dilatation
      (ectasia) and persistent distortion of ductal architecture. Ectasia was most
      severe in the proximal ducts near the urethra and in prostates 17 weeks or older
      at the end of 1 month of DES treatment. The clinical consequences of early
      alteration of prostatic ductal architecture and development are potentially
      deleterious, as men who were prenatally exposed to DES may be at increased risk
      for the development of prostatic disease.

PMID- 8560955
TI  - Differential expression and localization of integrins and CD44 in the membrane
      domains of human uterine epithelial cells during the menstrual cycle.
AB  - Human uterine epithelium displays a distinctly polarized organization with basal,
      lateral, and apical plasma membrane domains. Although nonadhesive throughout most
      of the menstrual cycle, uterine epithelial cells allow attachment of trophoblast
      cells to their apical pole during embryo implantation. Development of the
      receptive state might involve expression of cell adhesion molecules and/or
      redistribution of such molecules with respect to their localization at the basal,
      lateral, and apical membrane domains of cells. Expression and distribution of
      alpha 1-, alpha 3-, alpha 5-, alpha 6-, beta one-, beta 3- and beta 4-integrin
      subunits as well as of CD44 were examined in the luminal epithelium of human
      endometrium by immunohistochemistry in different phases of the menstrual cycle.
      The luminal epithelium was found to express alpha 1-, alpha 3-, alpha 6-, beta 1
      , beta 4-integrin subunits and CD44. alpha l6-Integrin subunits and CD44
      displayed cycle dependency. The alpha 6-integrin subunits were detected in the
      basal membrane domains in all phases. However, in correlation with increasing
      expression during the secretory phase of cycle, these subunits newly appeared in
      the lateral membranes of epithelial cells. CD44 showed increased expression in
      the secretory phase but was always restricted to the lateral membranes. The
      conspicuous behavior of alpha 6-integrin subunits and CD44 is discussed with
      respect to its possible functional significance for embryo implantation, and in
      relation to a hypothesis postulating that steroid-controlled master genes direct
      the acquisition of the receptive state of the luminal uterine epithelium by
      changing elements of the apicobasal polarity of these cells.

PMID- 8560957
TI  - A morphological and ultrastructural study of the paracloacal (scent) glands of
      the marsupial Metachirus nudicaudatus Geoffroy, 1803.
AB  - Morphological and ultrastructural features of the paracloacal glands of
      Metachirus nudicaudatus are described. Two pairs of glands, one on the right and
      the other on the left of the anal canal, are formed, each consisting of a major
      and a minor portion. Their wall is made up of three layers: a mucosal, a muscular
      and an external capsule. The inner one is a mucosa the epithelium of which
      contains holocrine cells characterized by lipid droplets and intermediate
      filaments. The surrounding vascular lamina propria contains flattened tubular
      apocrine glands whose epithelial cells contain abundant endoplasmic reticulum,
      prominent Golgi complexes and numerous secretory granules. The middle layer is
      formed by skeletal striated muscle and the outer (third layer) consists of dense
      connective tissue. Each gland originates from a single duct. Transverse sections
      show that each duct, except in the female major gland, is in fact formed by a
      duct system. One of these ducts comes from the central cavity, lined by holocrine
      epithelium, and the others result from the branched tubular glands of the lamina
      propria.

PMID- 8560956
TI  - Estrogen effects on lymphoid tissue in neonatal and adult female mice.
AB  - Outbred female mice of the NMRI strain were treated with daily doses of
      diethylstilbestrol (DES; 0.1-10 micrograms), estradiol-17 beta (E2; 5
      micrograms), testosterone (T; 5 or 25 micrograms), progesterone (P; 100
      micrograms), corticosterone (CC; 10 or 50 micrograms), or olive oil (controls)
      for the first 5 days after birth. Animals were killed on day 6 after birth, at 2,
      4, and 8 weeks or at 4 and 6 months. Only CC resulted in reduced thymus index
      weight (IW, mg organ weight/g body weight) on day 6 while the estrogen-induced
      reduced IW was secondary to a reduced body weight. Four-week-old and older
      estrogen-treated females had increased thymus IW (1.8-fold at 8 weeks after 5
      micrograms DES/day neonatally) which was still seen at 6 months. Estrogen-induced
      thymus enlargement also occurred in 8-week-old inbred NMRI females and in females
      belonging to the BALB/c strain. Thymus IW in 8-week old T-, P- and CC-treated
      females was as in controls. The leukocyte counts in blood and bone marrow were
      lower in DES females than in controls. The responses (thymus IW, peripheral blood
      leukocyte count) of 8-week-old females to ovariectomy and challenge with DES were
      different in DES females and in control females. The mitogen response of spleen
      lymphocytes and thymocytes was similar in controls and DES females. An anomaly in
      the hypothalamic-pituitary-gonad-thymus axis of adult, neonatally estrogen
      treated females might explain the thymus enlargement.

PMID- 8560958
TI  - Mild age-related changes in the dentate gyrus of adult rhesus monkeys.
AB  - Memory and cognitive performance decline with advancing age in humans. Rhesus
      monkeys show a similar age-related memory deficit. Since the functional
      neuroanatomy of the temporal lobes in the two species is similar, and since the
      circuits of the temporal lobes are known to be involved in memory function, we
      undertook a study of the anatomical characteristics of synapses in the dentate
      gyrus of the rhesus monkey throughout the adult life span. Light- and electron
      microscopic examinations were carried out on the dentate gyrus of 10 adult rhesus
      monkeys (4-35 years) to determine the effect of age on the thickness of the
      molecular layer and on axon terminals in the outer portion of the molecular
      layer. The thickness measurements were made on 100-microns-thick Vibratome
      sections and on 1 micron-thick Araldite-embedded sections. A total of 100
      electron micrographs covering a test area of 3,600 microns2 for each monkey were
      taken in the outer portion of the molecular layer. Counts of axon terminals
      synapsing with dendritic spines or shafts, measurements of the cross-sectional
      area of these terminals, and the length of the postsynaptic density were taken on
      enlarged prints. The thickness of the molecular layer remained unchanged
      throughout adulthood. Statistical analysis revealed no overall age-associated
      loss of synapsing axon terminals or shrinkage of the cross-sectional areas of
      their profiles. Further, there was no loss in the total number of synapses
      (axospinous plus axodendritic) or any change in the lengths of their postsynaptic
      membrane densities. However, when axodendritic (shaft) synapses (which constitute
      13% of the total) were considered separately, a statistically significant age
      related loss was detected. Qualitative observations revealed that older monkeys
      had a moderate number of dystrophic myelinated axons and corpora amylacea located
      in astrocytic processes in the outer portion of the molecular layer, features not
      present in young monkeys. Also, glial cells and pericytes showed age-associated
      accumulation of lipofuscin-like inclusions. A single occurrence of a structured
      inclusion body in a dendrite was observed in a 10-year-old monkey. In conclusion,
      most synaptic measures in the dentate gyrus remain stable throughout adulthood of
      rhesus monkey and there are relatively few other age-related changes. The small
      age-associated loss of axodendritic synapses is only apparent following separate
      statistical treatment of these synapses. The functional significance of this loss
      is unclear since it would result in only 3% reduction in total synapses (shaft
      plus spinous) from 4 to 35 years of age, the maximal life span of the rhesus
      monkey.

PMID- 8560959
TI  - Sensory receptors situated in the interphalangeal joint capsule of the fingers of
      the bonnet monkey (Macaca radiata).
AB  - Using bonnet monkeys (Macaca radiata) the content, location and types of sensory
      endings with regard to interphalangeal joints of the fingers of the hand were
      studied. Use of the modification of Barker and Ip [J Physiol (Lond) 1963;124: 476
      488] of the de Castros silver method showed that the Paciniform/Pacinian
      corpuscles are almost the exclusive encapsulated receptors in this tissue. Free
      nerve endings are present. Using serial paraffin sections stained with the May
      Grunwald-Giemsa stain, the proximal interphalangeal joint capsules were
      reconstructed. This confirmed the results of the study using teased preparations
      stained by the Barker and Ip method. In addition it was shown that the
      encapsulated endings were situated exclusively in the lateral and ventral aspects
      of the joint capsule. The number of lamellae of these encapsulated endings varied
      from as few as three to more than fifty. It is suggested that the contribution of
      these various receptors to kinaesthesis can depend on such factors as their
      relationship with tendons and skin.

PMID- 8560960
TI  - Terminal distribution of the branch termed Ramus communicans cum nervo
      glossopharyngeo of the facial nerve and its morphological significance.
AB  - It has already been clarified that the branch termed Ramus communicans cum nervo
      glossopharyngeo of the facial nerve in the current Nomina anatomica was in fact
      one of the branches of the glossopharyngeal nerve that ran towards the auricle
      [Kawai et al., 1989]. For this investigation, using 5 head sides including 3 with
      this branch, the author studied the course and the terminal distribution of this
      branch and compared the data with those of the usual vagal auricular branch which
      is known to be distributed into the auricle. As a result, the author confirmed
      that the branch in question was distributed into the cutaneous layer of the
      concha of the auricle and the posterior wall of the external acoustic meatus,
      into which the vagal auricular branch is usually distributed, and that the usual
      vagal or glossopharyngeal auricular branch existed simultaneously with the branch
      in question in 3 cases. These results suggest that this branch of the
      glossopharyngeal nerve does not appear simply as a compensatory branch in place
      of the usual vagal auricular branch.

PMID- 8560961
TI  - The fine vasculature of the rat mandibular joint.
AB  - There is no detailed description of the fine vasculature of the rat mandibular
      joint in the literature. The gross vasculature of the cephalic area and of the
      mandible is known, but without particular emphasis on the joint itself. This
      article describes the fine vasculature of the rat mandibular joint, using
      transverse (coronal) and sagittal thick sections of specimens injected with India
      ink and analyzed with light microscopy. The main vascular supply to the joint
      comes from the rostral and caudal aspects. Medially, the joint is directly
      vascularized by vessels from the lateral pterygoid muscle. Rostrally, the
      synovial membrane and the bilaminar zone of the disc are supplied by articular
      branches from the rostral deep temporal vessels, terminal branches of the
      maxillary artery. Caudally, the rich synovium of the retrodiscal pad and the
      bilaminar zone are supplied by the articular branches of the caudal deep temporal
      artery, a branch of the maxillary artery. Venous return is into the short, but
      large retroarticular vein which empties into the maxillary vein together with the
      vein from the transverse sinus exiting from the postglenoid foramen. Intra
      articular synovial membranes own rich venous plexuses, and are lined by a dense
      capillary network. The central part of the fibrous articular disc is avascular in
      adult rats, and is circumferentially lined by a rim of capillaries from the
      bilaminar zone.

PMID- 8560962
TI  - Fine structure of the epidermal basement membrane of the lip: applications of
      dithiothreitol separation and ultrathin frozen sectioning.
AB  - The fine structure of the epidermal basement membrane at the electron-microscopic
      level has already been defined. To obtain more details, two techniques,
      dithiothreitol separation and ultrathin frozen sectioning, were applied either
      alone or in combination. Negatively stained ultrathin sections showed a much
      thicker lamina densa than ordinary plastic-embedded sections. In the lamina
      lucida, bridging filaments and subbasal dense plates were observed in negative
      images. After the treatment with dithiothreitol, the lamina densa could be peeled
      off mechanically from the underlying dermis, and the anchoring fibrils were
      pulled off the dermis, preserving the connection with the lamina densa. With this
      specimen, bundles of anchoring fibrils were observed clearly and their lengths
      could be measured. Negatively stained ultrathin sections of dithiothreitol
      separated specimens showed the fine structure of the lamina lucida. Bridging
      filaments in the lamina lucida were resolved by negative staining.

PMID- 8560963
TI  - Accumulation and massive cell death of polymorphonuclear neutrophils in the
      developing bone marrow of the mouse: a histological study.
AB  - Accumulation and cell death of neutrophils were studied by light and electron
      microscopy in neonatal mouse bone marrow. At the beginning of bone marrow
      hematopoiesis, the marrow cavity contained a large number of polymorphonuclear
      leukocytes. Polymorphs comprised approximately 75% of the total nucleated cells
      in the hematopoietic compartment of the newborn marrow, the majority being
      neutrophils. Mature neutrophils were sometimes crossing the endothelium of the
      marrow blood sinus. Neutrophils in neonatal marrow show features typical of
      apoptosis, e.g. formation of nuclear pockets and blebs, margination of compact
      nuclear chromatin to form sharply circumscribed masses, condensation of
      cytoplasm, and convolution of cell outlines. Dying neutrophils were devoured and
      digested by phagocytes. The occurrence of large-scale neutrophil death and
      removal of neutrophils by phagocytes in neonatal bone marrow are discussed in
      relation to programmed cell death in development of the fetal hematopoietic
      system.

PMID- 8560964
TI  - Innervation of the human vaginal mucosa as revealed by PGP 9.5
      immunohistochemistry.
AB  - In order to obtain a description of the innervation of the vaginal wall we
      employed an antiserum against the general neuronal marker, protein gene product
      9.5, on normal human vaginal mucosa. Specimens were taken from the anterior and
      posterior fornices, from the anterior vaginal wall at the bladder neck level and
      from the introitus vaginae region, and then processed for indirect
      immunohistochemistry. All regions studied revealed a profound innervation,
      although regional differences were noted. The more distal areas of the vaginal
      wall had more nerve fibers compared to the more proximal parts. Also, biopsies
      from the anterior wall generally were more densely innervated than the posterior
      wall. Some large nerve coils were observed in lamina propria of the anterior wall
      as well as gatherings of thick-walled medium-sized blood vessels. Free
      intraepithelial nerve endings were only detected in the introitus vaginae region.
      These fibers were very thin, always varicose and could be observed just a few
      cell layers from the surface. In this part of the vagina, protein gene product
      9.5 antibodies also stained cells within the basal parts of the epithelium. These
      cells were also neurone-specific enolase positive and resembled, from a
      morphological point of view, Merkel cells.

PMID- 8560965
TI  - Anti-Leu-19 is a marker for nervous tissue in the mucosa of the human rectum.
AB  - Despite numerous investigations on the enteric nervous system, the knowledge
      about the mucosal innervation of the human rectum and colon is very shallow and
      mainly based on ultrastructural studies. We performed an enzyme (NADH-Ach) and
      immunohistochemical (NF, synaptophysin, anti-Leu-19) study on cryostat sections
      of the human rectal mucosa in order to study the possible additional
      characteristics of the mucosal innervation in depth. Enzyme histochemistry
      reveals positively staining fibers in the muscularis mucosae. Staining with
      antibodies against neurofilaments and synaptophysin reveals positively staining
      fibers in the lamina propria and muscularis mucosae. The latter staining is
      comparable with the findings obtained with anti-Leu-19. The monoclonal antibody
      anti-Leu-19 is characterized by a nerve-like staining in the mucosa revealed by
      nerve-like fibers from the plexus submucosus internus (Meissner) penetrating the
      muscularis mucosae, and creating a real plexus of fine twisted fibers in the
      lamina propria, around the crypts and underneath the epithelium. The distribution
      of the mucosal nerve-like pattern in the areas with mucosa-associated lymphoid
      follicles differs from the pattern observed in the lamina propria in between.
      Since the monoclonal antibody anti-Leu-19 and the monoclonal antibody NKH1a show
      a great similarity, we were interested also in the possible relation between the
      nerve like mucosal staining pattern and the lymphocytic population. Comparing the
      distribution pattern of anti-Leu-19 with other lymphocytic markers, there was an
      apparent similarity with the distribution of the T-helper subgroup. Our data
      indicate that the monoclonal antibody anti-Leu-19 shows a nerve-like staining
      pattern in the mucosa.

PMID- 8560966
TI  - Investigation of the blood-ganglion barrier properties in rat sympathetic ganglia
      by using lanthanum ion and horseradish peroxidase as tracers.
AB  - Vascular permeability in various rat sympathetic ganglia, including superior
      cervical ganglia, thoracic ganglia and the celiac-mesenteric ganglia (CMG)
      complex, was investigated by using lanthanum and horseradish peroxidase (HRP) as
      tracers with special attention to the neuronal and small granule-containing (SGC)
      cell area. After lanthanum perfusion, lanthanum tracer was present within the
      lumen of blood vessels. No lanthanum depositions were found in the extravascular
      space surrounding neurons in the superior cervical and thoracic ganglia. By
      contrast, an accumulation of lanthanum was observed in both luminal, abluminal
      and subendothelial surface of blood vessels in neuronal and SGC cell areas of the
      CMG complex and surrounding SGC cells in superior cervical ganglia. Injecting HRP
      revealed that all blood vessels of various sympathetic ganglia, either in
      neuronal or in SGC cell areas, were impermeable to HRP. HRP reaction product was
      limited to the vascular lumen and macrophages. The escape of HRP was obstructed
      by the junctional complex at intercellular clefts of endothelia and also by the
      diaphragms of the fenestrated capillaries associated with SGC cells. We conclude
      that there are different properties in the blood-ganglion barriers among rat
      sympathetic ganglia: (1) continuous capillaries in superior cervical ganglia and
      thoracic ganglia provide an efficient blood-ganglion barrier that prevents the
      penetration of tracers, and (2) capillaries in the CMG complex and in regions of
      the superior cervical ganglia that contain SGC cells possess a selective blood
      ganglion barrier that discriminates between tracers based on their molecular
      sizes.

PMID- 8560967
TI  - Alcohol intake effects on the dorsal vagal complex of the rat: a cellular
      morphometric study.
AB  - We have analyzed the morphometric effects on the dorsal vagal complex (DVC) of
      the rat of alcohol exposure and/or hypoproteic diet intake during 8 weeks. In the
      area postrema (AP), alcohol treatment (combined with normal isoproteic or
      hypoproteic diet) caused a significant decrease in karyometric parameters. In the
      dorsal motor nucleus of the vagus (DMV) and nucleus tractus solitari (NTS), the
      alcohol isoproteic intake (AI) produced an increase in neuron size (expressed by
      an increase in the neuronal nuclear area and the cell/neuropil coefficient). The
      hypoproteic diets produced a reduction in the global volume of each structure of
      the DVC which was accompanied by a decrease in global brain volume. These results
      indicate that after 8 weeks of treatment, alcohol is the main cause of the
      morphometric alteration found in the DVC, while variations in the amount of
      protein intake appear to produce global effects on the whole brain.

PMID- 8560968
TI  - Relationship of the mechanical properties of the cat inferior oblique muscle to
      the anatomy of its motoneurons and nerve branches.
AB  - Physiologically, the contractile characteristics and electromyography (EMG) of
      cat inferior oblique (IO) muscle fibers supplied by the medial and lateral IO
      muscle nerve branches were studied by direct nerve stimulation. Anatomically, the
      brain stem locations and sizes of IO motoneuron soma were evaluated after
      retrograde labeling by horseradish peroxidase (HRP) through whole IO muscle
      nerves and/or through each medial or lateral IO muscle nerve branch. Stimulation
      of the lateral nerve branch elicited significantly (p < 0.005) slower twitch
      contraction times (8.0 +/- 1.5 ms) and lower fusion frequencies (217 +/- 46 Hz)
      than when the medial branch of the IO nerve was stimulated (average twitch
      contraction time = 6.8 +/- 1.1 ms; average fusion frequency = 260 +/- 34 Hz). The
      EMG wave shape responses in the global and orbital layers could be differentiated
      when the individual nerve branches were stimulated, but the response differences
      were not consistent among animals. The average diameter of IO motoneuron soma
      with axons in the lateral branch of the nerve were significantly smaller (p <
      0.001) than the average diameter of those IO motoneuron soma associated with the
      medial branch of the nerve (27.9 +/- 7.2 vs. 32.9 +/- 7.2 microns). Regardless of
      which nerve branch was labeled, the full range of motoneuron soma sizes was
      found, and these were distributed throughout the IO subdivision of the oculomotor
      nucleus. These findings showed that muscle contraction time and motoneuron soma
      diameter were correlated with the IO nerve branch subjected to stimulation or
      exposed to HRP. But no topographic organization of motoneurons was found within
      the IO division of the oculomotor nucleus.

PMID- 8560969
TI  - Epithelio-stromal interactions in neonatal hamster bronchioles: morphology and
      distribution of epithelial foot processes and their possible relation to
      epithelial growth inhibition.
AB  - Morphology and distribution of epithelial foot processes (FP) were studied in
      hamster neonatal lung bronchioles. To correlate them with growth, bronchiolar
      mitotic index was determined, rat small intestine used as a reference tissue and
      the distribution of foot processes compared to the distribution of
      immunoreactivity against proliferating cell nuclear antigen (PCNA). In
      bronchioles, where growth occurs through dispersed mitoses, FP also occur
      dispersed throughout the whole perimeter of the epithelium; whereas in small
      intestine, where growth is localised in a specific region (crypts), FP are
      likewise confined to a distinct, but different, zone (villi). Staining the
      bronchioles for PCNA labels dispersed grouplets of nuclei; most of which being
      only weakly stained. In the intestines, strong immunostaining mainly occurs in
      the crypts, while the villi mainly display a weak nuclear stain. Additionally, in
      both types of tissue the distribution of FP and weak PCNA staining are parallel.
      Thus, an apparent association between FP, lack of proliferation and nucleoplasmic
      PCNA staining arises; the basis of which being presently unclear. However, a
      possible interrelating factor might be a growth inhibitory influence of epithelio
      stromal interactions on the epithelial cells.

PMID- 8560970
TI  - Presence and possible implications of open-ring centrioles, multiple basal
      centrioles and basal cilia in neonatal hamster bronchioles.
AB  - In studying epithelio-stromal interactions in the neonatal hamster lung, basal
      centrioles, basal cilia and open-ring centrioles attracted our attention. The
      same structures are also found in bronchiolar epithelium of a 3-week-old fawn
      hooded rat, indicating that they are not specific phenomena of hamster lung.
      Although cells with basal centrioles are not common, they are more readily
      observed in a sample of bronchioles at the second postnatal week as compared to
      the fourth neonatal day. The centrioles may often possess two satellites and
      function as microtubule organizing centers (MTOC). Open-ring centrioles are
      mature structures and also serve as MTOC. Apparently, triplets may de novo be
      added to and/or degraded from an open-ring centriole. The basal cilia and the
      cilia in the ciliated vacuoles/cysts, have a normal axonemal structure and may
      have a common origin from the basal centrioles. It is, however, unclear whether
      or not they are primary-like cilia. In addition, presence of the multiple basal
      MTOC and some morphologic features point to a high microtubule-associated
      vesicular transport activity and probably indicate an elevated interaction with
      the interstitium; thus, the cells have a different polarization then normal
      ciliated cells.

PMID- 8560971
TI  - Basement membrane formation of fetal mouse intestinal epithelial cells in
      organoid cultures.
AB  - Basement membrane formation of fetal mouse intestinal epithelial cells was
      investigated in organoid cultures. Intestinal cells were dissociated with a
      commercial collagenase/dispase preparation, and the cells were grown at high
      density on a membrane filter at the interface between the medium and air. This
      type of culture allows the histotypical reorganization of cells. After 2 days in
      culture, epithelial cells began to accumulate on the surface, in particular the
      periphery of the culture. These cells were usually cuboid, and small vesicles
      were formed in the center of the culture. Laminin-positive material was observed
      at peripheral sites. However, no basement membrane could be identified beneath
      the epithelial cells at the electron-microscopic level. After 3 days, epithelial
      cells that had gathered at the periphery became columnar in shape. Laminin
      positive material extended across the surface of the culture. However, the
      vesicles formed in the center of the culture were not associated with laminin
      positive material. Basement membrane was observed by electron microscopy at some
      sites beneath groups of epithelial cells, but did not extend continuously beneath
      these cells. Some epithelial cells made contact with the underlying mesenchymal
      cells through the discontinuous basement membrane via intercellular contacts.
      After 5-6 days, the surface of the culture was almost completely covered with
      epithelial cells and, at some sites, villus-like structures were visible. Laminin
      positive material was clearly detectable under epithelial cells, as well as
      around epithelial vesicles located in the center of the culture. By electron
      microscopy, basement membrane was clearly visible between the epithelial and
      mesenchymal cells. After 9 days, villus-like structures were rarely observed.
      After 3 weeks, the cell mass had become smaller and villi had disappeared.
      Basement membrane was extensively folded and no basement membrane was visible at
      some sites. Formation of basement membrane by epithelial cells in monolayer
      culture occurs in an incomplete and irregular manner. It occurs rapidly in
      organoid cultures that include mesenchyme and epithelium. The organoid culture
      used here should be a useful tool for studies of the formation and degeneration
      of the basement membrane as well as interactions between the epithelium and
      mesenchyme.

PMID- 8560972
TI  - White matter microglia produce membrane-type matrix metalloprotease, an activator
      of gelatinase A, in human brain tissues.
AB  - Membrane-type matrix metalloprotease (MT-MMP) is an activator of gelatinase A
      (MMP-2), which has previously been found in carcinoma cells. We examined non
      neurological and Alzheimer's disease brain tissues for MT-MMP by
      immunohistochemistry and in situ hybridization. The anti-MT-MMP antibodies gave
      positive staining of brain microglial cells in all the brain tissues. Positively
      stained microglia were found only in the white matter. The cells producing MT-MMP
      protein were also shown to be white matter microglia. These results provide
      further evidence that activated gelatinase A, which may be a processing enzyme
      for degradation of beta-amyloid protein, may be produced in white matter
      microglia.

PMID- 8560973
TI  - Experimental model of chronic tonsillar herniation associated with early stage
      syringomyelia.
AB  - This report describes an experimental model of chronic tonsillar herniation and
      its effects on the spinal cord. In ten rats, a small piece of chemically induced
      mammary cancer was transplanted to the supraoccipital bone. In all cases, the
      transplanted cancers grew into the posterior fossa, destroying the supraoccipital
      bone and compressing the cerebellum extradurally. In six of the ten rats,
      tonsillar herniation was observed at 8-14 weeks after transplantation. Transdural
      infiltration of the tumor cells was not apparent in any animal. In those rats
      with tonsillar herniation (n = 6), the spinal cord from the C5 to the T8 segments
      showed enlargement of the central canal without exception. Histological
      examination revealed the following changes: stretching and thinning of the
      ependymal cells; swelling of the astrocytic processes; and extra-cellular edema,
      predominantly in the dorsal gray matter, but also in the ventral inner portion of
      the dorsal column. In the control group (n = 4) and those rats without tonsillar
      herniation (n = 4), such histological changes of the spinal cord were not
      observed. Although the lesions can not be regarded as representing mature
      syringomyelia, they most likely constitute an earlier evolutionary stage.

PMID- 8560974
TI  - Ultrastructural studies of cerebral vascular spasm after cardiac arrest-related
      global cerebral ischemia in rats.
AB  - The present investigation was undertaken to study the ultrastructural morphology
      of brain blood vessels during vasospasm following total cerebral ischemia. Global
      cerebral ischemia was produced in rats by compression of the cardiac vessel
      bundle (i.e., cardiac arrest) using a metal hook that was introduced into the
      mediastinum. Ischemia lasted for 10 min with blood recirculation for 6, 12 and 24
      h. Rat brains were perfusion-fixed and regions from the cerebral cortex and
      associated leptomeningeal vessels were evaluated by scanning and transmission
      electron microscopy. We noted three general vasoconstrictive responses in vessels
      of various sizes including veins and arteries. These alterations related to the
      smooth muscle cell arrangement associated with each constricted vessel including
      a circumferential, and longitudinal arrangement, or a combination of both types.
      Other features in the three types of vasoconstricted vessels included thickening
      of the vessel basement membranes with increased endothelial microfilaments and
      vesicular profiles. Our studies present evidence that ischemia of 10-min duration
      with blood reflow for 6, 12 and 24 h produces profound and variable vasospastic
      changes in some but not all vessels. These vascular alterations are thought to be
      caused in part by vasoactive substances released both by endothelial and blood
      cells and by perivascular cellular elements in response to the ischemic episode.

PMID- 8560975
TI  - Immunogold labelling of paired helical filaments and amyloid fibrils by specific
      monoclonal and polyclonal antibodies.
AB  - Senile plaque and paired helical filament (PHF) formation are characteristic of
      Alzheimer's disease, but the mechanisms leading to these lesions still remain
      unclear. To understand them better, we have performed different immunolabellings
      of amyloid protein and PHF. We describe a very specific immunodetection of PHF
      with AD2, a monoclonal antibody directed against a hyperphosphorylated epitope of
      PHF-tau, and use double immunolabelling to show that PHF and plaque amyloid are
      discretely labelled by different antibodies. We also discuss different mechanisms
      of PHF maturation.

PMID- 8560976
TI  - Histochemical study of Ca(2+)-ATPase activity in ischemic CA1 pyramidal neurons
      in the gerbil hippocampus.
AB  - Although cytosolic Ca2+ accumulation plays a pivotal role in delayed neuronal
      death, there have been no investigations on the role of the cellular Ca2+ export
      system in this novel phenomenon. To clarify the function of the Ca(2+)-ATPase
      activity of CA1 pyramidal neurons was investigated ultracytochemically in normal
      and ischemic gerbil hippocampus. To correlate enzyme activity with delayed
      neuronal death, histochemical detection was performed at various recirculation
      times after 5 min of ischemia produced by occlusion of the bilateral carotid
      arteries. At 10 min after ischemia, CA1 pyramidal neurons showed weak Ca(2+)
      ATPase activity. Although enzyme activity had almost fully recovered 2 h after
      ischemia, it was reduced again 6 h after ischemia. Thereafter, Ca(2+)-ATPase
      activity on the plasma membrane of CA1 pyramidal neurons decreased progressively,
      losing its localization on day 3. On day 4 following ischemia, reaction products
      were diffusely scattered throughout the whole cell body. Our results indicate
      that, after once having recovered from ischemic damage, severe disturbance of the
      membrane Ca2+ export system proceeds from the early stage of delayed neuronal
      death and disturbs the re-export of accumulated cytosolic Ca2+, which might
      contribute to delayed neuronal death. Occult disruption of Ca2+ homeostasis seems
      to occur from an extremely early stage of delayed neuronal death in CA1 pyramidal
      cells.

PMID- 8560978
TI  - Ischemic stress induces deposition of amyloid beta immunoreactivity in human
      brain.
AB  - The histoblot immunostaining technique for locating and characterizing
      amyloidogenic proteins was used to obtain information about the relationship of
      cerebral ischemia/hypoxia to the accumulation of amyloid beta protein (A beta).
      We investigated brains of 131 subjects (ages 25-94 years, mean 72 years). Three
      distribution patterns of A beta immunoreactivity were identified: (1)
      colocalization with diffuse and neuritic plaques of Alzheimer's disease (AD) and
      aging; (2) diffuse punctuate deposits in the cerebral cortex in association with
      small vessel cerebral vascular disease ; and (3) cerebral cortical accumulation
      localized to arterial boundary zones and other regions susceptible to
      ischemic/hypoxic injury designated "stress-induced deposits" (SID). SID were not
      identified in tissue sections by immunohistochemical, Congo red or Bielschowsky
      silver techniques; no histological abnormalities were present in adjacent
      formalin-fixed tissue sections, SID occurred in subjects with histories of
      cerebral ischemia, and severe orthostatic hypotension. There was also an
      association with aging in general and with the incidence of neuritic plaques
      specifically. These latter findings are consistent with the hypothesis that brain
      ischemia/hypoxia plays a role in the pathogenesis of AD.

PMID- 8560977
TI  - Role of the endothelial cytoskeleton in blood-brain-barrier permeability to
      protein.
AB  - The role of the cytoskeletal elements, microfilaments and microtubules in
      cerebral endothelial permeability to protein during steady states was
      investigated by studies of cerebrovascular permeability to horseradish peroxidase
      (HRP) in rats pretreated with cytochalasin B or colchicine, agents known to
      disrupt microfilaments and microtubules, respectively. In addition, the effect of
      colchicine pretreatment on the alterations in cerebrovascular permeability that
      occur in acute hypertension were studied. Rats infused with cytochalasin B showed
      increased cerebrovascular permeability to HRP in multifocal areas of the
      ipsilateral hemisphere. Most of the permeable vessels were arterioles; however,
      capillaries and venules also showed increased permeability. Ultrastructural
      studies of permeable vessels showed HRP in all layers of vessel walls and in
      endothelial and smooth muscle cell pinocytotic vesicles, which were increased in
      number. Although segments of interendothelial spaces were labeled by tracer,
      continuous labeling of interendothelial spaces from the luminal to the abluminal
      end was not seen and tight junctions were not disrupted. Normotensive rats
      pretreated with colchicine showed no alteration in cerebrovascular permeability
      to HRP. Colchicine pretreatment attenuated the permeability alterations that were
      observed in acutely hypertensive rats. This study demonstrates that integrity of
      endothelial actin filaments is important for maintenance of the blood-brain
      barrier to protein during steady states since increased permeability occurred in
      the presence of an actin disrupting agent. The microtubular network had no
      demonstrable role during steady states; however, disruption of the microtubular
      network had a protective effect and prevented the development of alterations in
      permeability to protein in acute hypertension.

PMID- 8560979
TI  - Tau protein immunoreactivity in muscle fibers with rimmed vacuoles differs from
      that in regenerating muscle fibers.
AB  - To determine whether tau protein found in muscle fibers with rimmed vacuoles and
      in regenerating fibers was phosphorylated, we examined eight muscle biopsy
      samples containing rimmed vacuoles (from five patients with distal myopathy with
      rimmed vacuole formation and three patients with inclusion body myositis) and
      three muscle biopsy samples from patients with Duchenne muscular dystrophy
      containing numerous regenerating fibers. Although both rimmed vacuolated and
      regenerating fibers had increased immunoreactivity against tubulin and tau
      protein, tau protein in the former was more highly phosphorylated than that in
      the latter. While very few microtubules in muscle fibers with rimmed vacuoles
      were recognizable by electron microscopy, regenerating fibers, especially
      immature ones, contained numerous microtubules. Since tau protein found in
      vacuolated fibers is hyperphosphorylated, it can be considered to have reduced
      ability to bind tubulin molecules. Thus, the tau protein cannot stabilize
      microtubules, resulting in their depolymerization even in the presence of tubulin
      molecules.

PMID- 8560980
TI  - Microglial cells and amyloid beta protein (A beta) deposition; association with A
      beta 40-containing plaques.
AB  - Two distinct species of amyloid beta protein (A beta) with different carboxyl
      termini, A beta 40 and A beta 42(43), are deposited in plaques in the brains of
      patients with Alzheimer's disease and Down's syndrome. The relationship between
      these two forms of A beta and microglial cells was investigated in 16 subjects
      with Down's syndrome ranging in age from 31 to 64 years. The amount of A beta 40
      in plaques was low in persons under 50 years of age, even though high amounts of
      A beta 42(43) were present. Microglia were observed most commonly in plaques
      containing both A beta 40 and A beta 42(43) but less commonly in those with A
      beta 42(43) alone. The presence of microglial cells in plaques may be associated
      with the accumulation of A beta 40 and these cells may have a role in the
      production or processing of this particular molecular species.

PMID- 8560981
TI  - Neurotransmitters in the spinal cord dorsal horn in a model of painful neuropathy
      and in nerve crush.
AB  - We tested the hypothesis that neurochemical changes in the spinal cord dorsal
      horn associated with neuropathic pain states differ from those seen in
      association with non-painful neuropathies. Immunohistochemistry was performed on
      spinal cord sections from rats with a chronic constriction injury (CCI), which
      develop hyperalgesia, and from animals with a nerve crush injury, which do not
      develop hyperalgesia or other signs of a painful syndrome. Immunohistochemistry
      was quantified by computer-assisted densitometry. Calcitonin gene-related peptide
      (CGRP) immunoreactivity and substance P (SP) immunoreactivity were decreased from
      1 to 4 weeks after injury in CCI and from 2 to 6 weeks in crush. Gamma
      aminobutyric acid immunoreactivity was unchanged in both conditions at all time
      points. Met-enkephalin (Met-enk) immunoreactivity was increased in CCI and
      unchanged in crush. Although SP and CGRP are involved in pain transmission, we
      conclude that their decrease in immunoreactivity is not specific for the CCI
      model, but rather a more general event in nerve de- and regeneration. The
      increase in immunoreactivity for the opioid peptide Met-ink, however, was only
      seen in the late phase of CCI, and may be specific for conditions associated with
      neuropathic pain and its resolution.

PMID- 8560982
TI  - Axonal swellings in cerebellar white matter of groggy mutant rat.
AB  - In the groggy mutant rat, a number of axonal swellings appeared in the cerebellar
      white matter from 180 days of age onward. Since these axonal swellings were
      immunostained with an antibody against calbindin D28k, the axons forming these
      swellings were considered to belong to Purkinje cells. They were also
      immunostained with an anti-neurofilament antibody, and ultrastructurally
      characterized by the presence of myelin sheaths around them and abnormal
      accumulations of filamentous structures, mitochondria and smooth endoplasmic
      reticula (SER) in their axoplasm. The SER were considered to convey acid
      phosphatase (ACPase) to the swelling's axoplasm, where ACPase was set free from
      the SER throughout the axoplasm and engaged in the digestion of cytoplasmic
      organelles. The groggy rat is useful model model for the study of the mechanism
      of the age-related formation of axonal swellings.

PMID- 8560983
TI  - A lysosomal marker for activated microglial cells involved in Alzheimer classic
      senile plaques.
AB  - One of the major histopathological lesions in brains of patients with dementia of
      the Alzheimer type (DAT) is the senile plaque. Although previous studies have
      shown that senile plaques are often accompanied by microglial cells, the role of
      these cells in DAT pathology is still unclear. In an immunohistochemical and
      immunoelectron microscopical analysis of DAT and control brain tissues we
      addressed this issue using two monoclonal antibodies (mAbs KP1 and 25F9) directed
      against lysosomal antigens in monocytes and macrophages. Whereas KP1 stained
      lysosomes in both resting and activated microglial cells, 25F9-staining was
      predominantly found in lysosomes of activated microglial cells in classic senile
      plaques. The number and size of 25F9-positive lysosomes in activated microglial
      cells was increased compared to 25F9-staining in unaffected areas in DAT and
      control sections. We conclude that mAb 25F9 is a unique and useful lysosomal
      marker, with a higher specificity than other known markers, for activated
      microglial cells associated with classic, but not with diffuse, senile plaques.

PMID- 8560984
TI  - Both apoptosis and necrosis occur following intrastriatal administration of
      excitotoxins.
AB  - To learn about the mechanisms of excitotoxic cell death in vivo, three different
      excitatory amino acid receptor agonists (kainic acid, quinolinic acid or
      quisqualic acid) were injected in the left striatum of adult rats. Brains were
      examined at 24 and 48 h after injection. Morphological and biochemical studies
      were performed using conventional stains, histochemistry, in situ labelling of
      nuclear DNA fragmentation, and agarose gel electrophoresis of extracted DNA.
      Large numbers of cells with cytoplasmic shrinkage and nuclear condensation or
      granular degeneration of the chromatin, and fewer cells with apoptotic morphology
      were distributed at random in the injured areas of the three groups of treated
      animals but not in rats injected with vehicle alone. A ladder pattern, typical of
      internucleosomal DNA fragmentation, was observed 24 h after treatment. This was
      replaced by a smear pattern, consistent with random DNA breakdown, at 48 h. These
      morphological and biochemical results suggest that prevailing necrosis together
      with apoptosis occur following intrastriatal injection of different excitotoxins.

PMID- 8560985
TI  - Cytomegalovirus infection of the brain in AIDS: a clinicopathological study.
AB  - Based on neuropathological findings, a retrospective case control study of 39
      patients with acquired immune deficiency syndrome (AIDS) and confirmed
      cytomegalovirus (CMV) infection of the brain is presented. Since 1989, the
      incidence has increased progressively and, in 1994, CMV was the most frequent
      opportunistic central nervous system (CNS) infection. Of the patients with CMV
      infections of the brain 16 had one or more coexisting secondary opportunistic
      and/or tumorous lesions in the CNS. Cerebral involvement by CMV was more frequent
      in patients with multiple extracerebral organ infections, while 7 among the 39
      reported cases showed isolated CMV infection of the brain. The evaluation of the
      clinical records of 21 patients revealed neuropsychiatric signs and symptoms in
      10, while these were absent in 11. All of these patients revealed various types
      of cerebral lesions related to CMV infection: ventriculitis, focal lesions, and
      microglial nodule encephalitis. The extent and distribution of cerebral lesions
      showed no significant correlations with clinical, radiological, or laboratory
      findings. Further clinicopathological studies are warranted to recognize CMV
      infections of the CNS and to allow earlier and more efficient treatment of this
      rather frequent complication of AIDS.

PMID- 8560986
TI  - Familial amyloid polyneuropathy associated with transthyretin Gly42 mutation: a
      quantitative light and electron microscopic study of the peripheral nervous
      system.
AB  - We performed extensive quantitative analyses of the peripheral nervous system
      (PNS) of two siblings with familial amyloid polyneuropathy (FAP) caused by a
      transthyretin (TTR) Gly42 mutation. Pronounced amyloid deposition was found in
      the sympathetic ganglia (SyG), dorsal root ganglia (DRG) and throughout the
      length of the peripheral nerve fibers with some accumulation in the more proximal
      portion. There was severe neuronal loss in the SyG and DRG together with nerve
      fiber depletion in the nerve trunk, while only a small amount of amyloid
      deposition with mild fiber loss was seen in the spinal roots. Sprouts of
      regenerating axons were very scanty even in the spinal nerves or roots. A teased
      fiber study mainly showed demyelinating fibers, but axonal degeneration was also
      present throughout peripheral nerves. An electron microscopic study showed fine
      amyloid fibrils in direct contact with the axoplasmic membrane of demyelinated
      axons and destruction of axons in some areas. Amyloid deposition within the PINS
      in this type of FAP resembled that in type I FAP (TTR Met30). However, direct
      axonal damage by amyloid fibrils appeared to be more prominent in our cases than
      in type I FAP. Lectin histochemistry using Ulex europaeus agglutinin I
      demonstrated preferential depletion of small neurons in the DRG and their primary
      afferent fibers in the spinal dorsal horn. Primary axonal degeneration and
      ganglionopathy due to amyloid deposition appear to be the pathogenetic mechanisms
      for peripheral neuropathy in this type of FAP.

PMID- 8560987
TI  - Lack of topographical relationship between sites of aluminum deposition and
      senile plaques in the Alzheimer's disease brain.
AB  - Aluminum has been presumed to be involved in the pathogenesis or etiology of
      Alzheimer's disease. Histochemical demonstration of aluminum in autopsy brains
      from Alzheimer's disease victims by means of the solochrome azurine method in
      combination with the methenamine silver technique revealed aluminum-related
      staining in some neocortical and hippocampal senile plaques and tangles, as well
      as in the cytoplasm and/or the nuclei of some neurons, and in the cytoplasm of
      endothelial cells of blood capillaries and pericytes around larger blood vessels.
      In double-stained samples (first with methenamine silver and then with solochrome
      azurine) only some plaques displayed the presence of aluminum, while others did
      not show any sign of the presence of the trace metal. The specificity and
      sensitivity of solochrome azurine staining was checked in paper spot-test and
      test-tube experiments combined with flameless atomic absorption
      spectrophotometry. The results suggest that aluminum is present in brain samples
      from Alzheimer's disease victims, but the structural localization indicates that
      it is not primarily involved in the etiology of the disease.

PMID- 8560988
TI  - Intracerebral vascular occlusion in familial erythrophagocytic
      lymphohistiocytosis: a case report of two siblings.
AB  - Neuropathological findings in two siblings with familial erythrophagocytic
      lymphohistiocytosis (FEL) are reported. Case 1 showed the typical
      neuropathological findings of FEL with lymphohistiocytic infiltration of the
      leptomeninges and perivascular spaces. A characteristic erythrophagocytosis was
      detected in inguinal lymph nodes, lung and bone marrow. Case 2 revealed
      calcification and necrotic lesions in the brain. In the necrotic areas,
      parenchymal calcification, vascular medial calcification, and occlusion of many
      vessels due to subendothelial fibrosis were detected. The areas of necrosis
      correlated with the distribution of occluded vessels. These changes were most
      prominent in putamen, internal capsule, thalamus and dentate nucleus.
      Hypercytokinemia is suspected to be the underlying mechanism for the clinical and
      laboratory findings in patients with FEL, although the relationship to the
      vascular pathology is unclear.

PMID- 8560989
TI  - Suprasellar meningioma with expression of glial fibrillary acidic protein: a
      peculiar variant.
AB  - A 24-year-old female presented with a 3-year history of a suprasellar and
      intraventricular solid midline process measuring about 3 x 4 cm. At surgery, this
      tumour was sharply delineated and of stone-like firmness and was removed
      completely. Histology suggested meningioma, featuring nests and cords of
      epithelium-like cells with prominent cytoplasm amidst abundant fibrous stroma
      with prominent lymphoplasmocellular infiltration. Immunocytochemically, the
      tumour cells expressed vimentin, S-100 protein, epithelial membrane antigen,
      cytokeratins, and most surprisingly, glial fibrillary acidic protein (GFAP).
      Ultrastructural investigation revealed abundant intermediate filaments and
      occasionally dense secretory granules in tumour cells with short, finger-like
      cytoplasmic processes joined by very rare small, but well-developed desmosomes.
      This tumour most likely represents a peculiar variant of meningioma with
      prominent production of GFAP, as previously described [Budka H (1986) Acta
      Neuropathol (Berl) 72: 43-54].

PMID- 8560990
TI  - Treatment of vaginal recurrence in endometrial cancer. A review.
AB  - BACKGROUND: We have reviewed the literature concerning vaginal recurrence in
      endometrial cancer with emphasis on prognostics and therapeutic results. Compared
      to the overall outcome of recurrences (11-17 per cent survive more than 3-19
      years) the survival rate of strictly vaginal recurrence appears significantly
      higher (up to 60-70 per cent survive more than 5 years). However, the prognosis
      deteriorates significantly in cases where recurrences prove to be more
      widespread. Other factors towards predicting a poor outcome are high age, high
      stage, high grade, detection of papillary carcinoma, rapid recurrence, location
      to the lower part of vagina, large tumor size, and previous radiation. METHODS:
      Different methods of initial treatment and cross-relations between most
      prognostic factors renders any ranking of prognostic factors almost impossible.
      RESULTS: Standard treatment of vaginal recurrence including combined external and
      intra vaginal radiation used for decades have been unable to improve survival
      rate. CONCLUSION: We suggest a more individualized treatment based on exact
      delineation of the disease.

PMID- 8560991
TI  - Effects of estradiol and interaction with progesterone or oxytocin on term human
      myometrial contractile activity.
AB  - BACKGROUND: To investigate the effects of estradiol (E2) alone and in combination
      with progesterone or oxytocin on contractile activity of term human myometrium in
      vitro. METHODS: Myometrial specimens were obtained from 24 term pregnant women
      not in labor who underwent elective cesarean. Biopsies were kept in ice-cold and
      oxygenated Hepes buffer and buffer containing different hormonal solutions. The
      biopsies were dissected and mounted in tissue baths at 37 degrees C and isometric
      tension was recorded. RESULTS: (1) Estradiol at 0.1 and 1 microgram/mL increased
      the contractile frequency (p < 0.01 for each), decreased the tonus (p < 0.05 and
      p < 0.01) and suppressed the activity area of contractions (p < 0.05 and p <
      0.01) as compared to control. (2) No significant differences in frequency and
      activity area of contractions between strips superfused with E2 plus progesterone
      and progesterone alone were recorded. Myometrial tonus was decreased by 0.1
      microgram/mL or 1 microgram/mL E2 plus progesterone as compared to progesterone
      alone (p < 0.05 and p < 0.01). (3) There were no significant differences in
      frequency between strips superfused with E2 plus oxytocin and oxytocin alone.
      Myometrial tonus was decreased by 0.1 microgram/mL or 1 micrograms/mL E2 plus
      oxytocin as compared with oxytocin alone (p < 0.05 and p < 0.01). Estradiol at
      0.1 microgram/mL or 1 micrograms/mL plus oxytocin reduced the activity area of
      contractions compared to oxytocin (p < 0.05 and p < 0.01). CONCLUSIONS: These
      data suggest that E2 had both stimulatory and inhibitory effects on term human
      myometrial contractility and that E2 altered the myometrial response to
      progesterone and oxytocin mainly by decreasing tonus.

PMID- 8560992
TI  - Births by younger and older mothers in a population with late and regulated
      childbearing: Finland 1991.
AB  - PURPOSES: The aims of this study were: first, to ascertain the characteristics of
      younger and older mothers in the Finnish population; second, to assess the health
      conditions pertaining to births and newborns according to maternal age groups.
      METHODS: The data, 26,373 primiparous and 38,895 multiparous women, came from the
      1991 nationwide Finnish birth register, and was completed using death and
      education registers. The younger (< 18 and 18-19 year olds) and older (35-39 and
      40 and over) mothers were compared to 20-34 year olds. Infant outcomes were
      studied by adjusting for mothers' social and obstetric background characteristics
      by using stepwise logistic regression. RESULTS: Births were rare among women
      younger than 18 years or 40 years or older. Younger primiparous mothers (less
      than 20 years) were less often married, more often had a lower social class
      background, and tended to live in Northern Finland and used antenatal care
      somewhat less. Their pregnancies, giving birth and infant outcomes were similar
      to those of 20-34 years old mothers. Most older mothers were women having their
      families late, rather than having big families. Older primiparas (35 years or
      older) were less likely to be married, were more often highly educated and lived
      in urban areas and in the most southern county. Older mothers had more problems
      during pregnancy and labor, and their infant outcomes were worse. CONCLUSIONS:
      Our study supports the notion that for young mothers giving birth is a social
      rather than a medical problem, whereas the reverse is true for older mothers.
      However, perinatal results for most older mothers are good.

PMID- 8560993
TI  - Gestation-adjusted projection of estimated fetal weight.
AB  - OBJECTIVE: To assess a technique for forward extrapolation of ultrasound
      estimated fetal weight to the time of delivery. METHODS: A total of 276 women who
      delivered within 35 days of ultrasound examination were studied. Fetal weight was
      estimated according to either Hadlock's formula for the biparietal diameter,
      abdominal circumference and femur length or Campbell's formula for the abdominal
      circumference. The extrapolation technique is based on the hypothesis that the
      fetal weight: median weight ratio remains constant in the third trimester. The
      weight estimates were either left unchanged or extrapolated to the time of
      delivery according to this method and compared with a technique described by
      Spinnato and colleagues (7, 8). The accuracy of the method was assessed by
      analysing the weight predictions in relation to the birth weights, using non
      parametric tests. RESULTS: The mean systematic error using our extrapolation
      method with Hadlock's weight formula was 5.9%, which was significantly better
      than using Spinnato's method (8.8%) or making no adjustment at all (-6.5%). The
      random errors were also significantly reduced (11.2% versus 12.3% and 12.3%, p <
      0.0005). With Campbell's formula, the mean systematic error from our method was
      3.8%, whereas the unadjusted formula would have yielded an error of -8.5% (p <
      0.001). The absolute errors with our technique were also significantly lower than
      those of the other methods. CONCLUSIONS: In the prediction of birth weight, an
      antenatal ultrasound estimation of fetal weight needs to be projected to the
      expected time of birth and for this it must take the time lapse to delivery into
      consideration. The method presented is able to accomplish this with simplicity
      and accuracy.

PMID- 8560994
TI  - The relationship between psychological distress during pregnancy and birth weight
      for gestational age.
AB  - BACKGROUND: Fetal growth may be determined by genetic as well as environmental
      factors. Whether psychological distress during pregnancy influences fetal growth
      is a matter of debate. MATERIAL AND METHODS: A prospective population-based study
      with repeated measures of psychological distress (General Health Questionnaire)
      during pregnancy, based on the use of questionnaires. Danish speaking women with
      singleton pregnancies attending antenatal care between August 1, 1989 and
      September 30, 1991 were eligible to the study (n = 8719). Of these women 5868
      women (67%) completed all questionnaires. The main outcome measure was fetal
      growth (assessed as birth weight for gestational age (continuous)) and birth
      weight below the 10th percentile of birth weight for gestational age (light for
      gestational age (LGA) (dichotomous). Gestational age was calculated primarily
      from an early ultrasound scan. Confounders were controlled using multivariate
      statistical methods. RESULTS: Birth weight for gestational age and risk of
      delivering a LGA baby were not associated with psychological distress, neither
      distress in 16th week nor in 30th week of pregnancy. CONCLUSION: To the extent
      that fetal growth can be explored at birth, the results indicate that
      psychological distress does not influence fetal growth.

PMID- 8560995
TI  - Plasma cyclic GMP concentrations and their relationship with changes of blood
      pressure levels in pre-eclampsia.
AB  - BACKGROUND: One of the possible mechanisms responsible for pre-eclampsia is a
      loss of efficiency of the L-arginine-nitric oxide pathway with subsequent
      inactivation of the guanylyl cyclases of the vascular smooth muscle cells. As a
      result there should be a decrease in plasma cyclic 3'-5' guanosine monophosphate
      (cGMP) concentrations in pre-eclampsia. We assessed the behavior of this
      nucleotid in the plasma of pre-eclamptic women. SUBJECTS AND METHODS: Sixteen pre
      eclamptic women, 16 normotensive pregnant women matched for gestational age and
      six nonpregnant controls were investigated. Arterial blood pressure was recorded
      at inclusion time and then once-a-day until the fourth day after delivery
      concomitantly with the collection of blood samples for determining plasma cGMP,
      atrial natriuretic peptides (ANP), creatinine, uric acid and platelet counts.
      Also 24 h urines were simultaneously collected to calculate renal clearance of
      cGMP. RESULTS: Before the initiation of antihypertensive treatment, plasma cGMP
      levels were significantly higher (p < 0.01) in pre-eclampsia women as compared
      both to pregnant normotensive controls and nonpregnant women (7.02 +/- 0.9 versus
      4.8 +/- 0.76 versus 1.93 +/- 0.15 pmol.ml-1, p < 0.01). Under antihypertensive
      treatment, cGMP levels decreased significantly (p < 0.05) to 5.48 +/- 0.9 pmol.ml
      1. The increase of plasma cGMP was associated with high ANP levels; the
      likelihood that a renal impairment could account for an increase in plasma cGMP
      was ruled out because the clearance of creatinine was not impaired. Similarly the
      possibility of a significant linear correlation between cGMP levels and blood
      pressure values or biological data was excluded in these women. CONCLUSION:
      Plasma cGMP concentrations are increased in pre-eclampsia. They decrease to
      control values when blood pressure returns to normal values; they indicate
      enhanced guanylyl cyclase activation by ANP and additional factors, but cannot be
      considered as a direct index of the severity of pre-eclampsia.

PMID- 8560996
TI  - Cervical ripening and induction of delivery by local administration of
      prostaglandin E2 gel or vaginal tablets is equally effective.
AB  - BACKGROUND: Prostaglandin E2 for local application has been widely used for
      preinduction cervical ripening in cases presenting with an unfavorable cervical
      state. The optimal way of administering prostaglandin E2, however, remains
      unclear. The aim of this study was to compare the effect of multiple application
      of 0.5 mg Minprostin intracervical Gel to the effect of 3 mg Minprostin vaginal
      tablets in priming the uterine cervix and inducing labor in an open, prospective,
      randomised study. METHODS: PGE2 was applied up to three times a day for two days
      until ripening was obtained or labor induced. In case no progress took place
      amniotomy was performed and i.v. oxytocin stimulation one hour later if
      necessary. A total of 208 pregnant women, consecutively admitted for induction of
      delivery, with Bishop Scores 0-5, were included. RESULTS: Minprostin gel (group
      I) and Minprostin tablets (group II) were equally effective in ripening the
      cervix. Delivery within 48 hours was achieved in 59% and 63% respectively. The
      mean number of applications was 2.6 (s.d. 1.6) and 2.7 (s.d. 1.3) respectively.
      In case more than four doses were required no further effect was seen on delivery
      rates. Rates of cesarean section (performed in 15% and 18% respectively), labor
      induction (3%/1%), drop outs (14%/12%) and failed inductions (10%/5%) were
      comparable. Patients in group I had a significantly lower demand for analgesia. A
      significantly shorter induction-delivery interval in group II was seen in
      patients with preinduction Bishop scores 3-5 compared to patients with Bishop
      scores 0-2. Side effects were few. Both procedures appear safe. CONCLUSIONS:
      Cervical ripening and induction of delivery by local administration of
      prostaglandin E2 gel or vaginal tablets in cases presenting with an unfavorable
      cervical state is equally effective.

PMID- 8560997
TI  - Premature rupture of the membranes (PROM) at term in nulliparous women with a
      ripe cervix. A randomized trial of 12 or 24 hours of expectant management.
AB  - OBJECTIVE: To compare maternal and neonatal outcomes after 12 or 24 hours of
      expectant management in healthy nulliparous women with a ripe cervix and PROM at
      term. DESIGN: A prospective, randomized study. LOCATION: Karolinska Hospital,
      Stockholm, Sweden. SUBJECTS: Two hundred and five healthy nulliparous women with
      singleton pregnancies, cephalic presentation, gestational duration 36 to 42
      weeks, randomized to 12 or 24 hours of expectant management after evaluation of
      the cervical score (> 5). If spontaneous labor did not occur, induction was
      performed with oxytocin after 12 or 24 hours, respectively. MAIN PARAMETERS:
      Maternal early morbidity and neonatal infections, obstetric intervention rate
      (cesarean section or instrumental delivery). RESULTS: The cesarean section rate
      was 4% in each group. The vacuum extraction rate was 21% in each group. Induction
      of labor was performed in 47% of the women allocated to 12 hours of expectant
      management vs 17% of the women allocated to 24 hours of expectant management (p <
      0.05). The maternal morbidity rate was almost negligible. Only a few fetal
      infections occurred and no difference was noted between the groups. CONCLUSIONS:
      In healthy nulliparous women at term with a ripe cervix, expectant management
      over 24 hours vs 12 hours resulted in fewer inductions of labor and no increase
      in instrumental deliveries, without any increase in neonatal or maternal
      morbidity.

PMID- 8560998
TI  - Effect of vaginal misoprostol application for cervical softening in pregnancy
      interruption before ten weeks of gestation.
AB  - OBJECTIVE: To determine the effect of vaginal misoprostol application for
      cervical dilatation and to determine the time taken for pregnancy interruption.
      METHODS: 200 micrograms misoprostol and gyno-flor vaginal tablet, employed to
      create acidic milieu, were applied into the posterior fornix of 40 women with
      gestational age of 5 to 10 weeks. Placebo was applied vaginally to 20 women who
      made up the control group. All cases were examined 5 hours later. The cervical
      dilatation, presence of fetoplacental material in the vagina, extrauterine
      cervical bleeding and the time necessary for dilatation and suction curettage
      were investigated. RESULTS: In 33 (82.5%) of the cases cervical bleeding, in 21
      (52.5%) of the cases fetoplacental material on the cervix and/or in the vagina
      were detected in women of misoprostol group, while neither cervical bleeding nor
      fetoplacental material on the cervix and/or in the vagina was detected in the
      placebo group. In the misoprostol group the time taken for the operation was
      significantly (p < 0.005) shorter than that of the control group. CONCLUSION:
      Vaginal application of misoprostol shortens the time needed for the termination
      of the gestation by its facilitating effect on cervical dilatation.

PMID- 8560999
TI  - Estrogen and progestagen modify the hemodynamic response to mental stress in
      young women.
AB  - OBJECTIVE: To evaluate separately the effects of estrogen and progestagen on the
      cardiovascular response to a standardized mental stress test. METHODS: Seven
      women were studied during the early follicular phase (day 1-4) of three different
      menstrual cycles after randomized oral administration of either 6 mg estradiol
      valerate or 15 mg norethisterone acetate or placebo. Heart rate and blood
      pressure were recorded at rest for 2 hours after administration and throughout
      the stress test. Forearm plethysmography was recorded at rest and during stress.
      RESULTS: Estrogen had no effect on heart rate or blood pressure at rest. After
      estrogen administration the increases in heart rate (delta 14 bpm/10 bpm; p <
      0.01) and diastolic blood pressure (delta 14 mmHg/9 mmHg: p = 0.06) from baseline
      to stress were augmented compared to those observed after placebo administration.
      Heart rate, systolic and diastolic blood pressures reached higher levels during
      stress after estrogen administration compared to placebo (delta 5 bpm, and delta
      7 mmHg and delta 5 mmHg respectively; p < 0.05). Estrogen administration also
      caused a prolongation of the diastolic blood pressure response to stress.
      Progestagen compared to placebo induced an increase in heart rate already at rest
      (delta 4 bpm; p < 0.01), and heart rate was maintained on a higher level
      throughout the stress test (p < 0.05). Blood pressure at rest and pressor
      responses to stress were not significantly changed after progestagen
      administration. CONCLUSIONS: The results indicate that estrogen is responsible
      for the enhanced cardiovascular responses to stress, whereas progestagen provokes
      a parallel upward shift of basal heart rate which is independent of level of
      activation.

PMID- 8561000
TI  - Endocervical cell retrieval following excisional treatment of CIN: a comparison
      study between large loop excision of the transformation zone and laser cone
      excision.
AB  - BACKGROUND: The purpose of our study was to compare laser cone excision with
      large loop excision of the transformation zone with particular respect to the
      retrieval of endocervical cells on follow-up cervical cytology. METHODS:
      Retrospective analysis of case records of 368 women who had large loop excision
      of the transformation zone and 188 women who had laser cone excision for
      suspected CIN changes at Middlemore Hospital, Auckland. RESULTS: The retrieval of
      endocervical cells on cervical cytology following large loop excision was 94.7%
      and 85.2% following laser cone excision. Laser cone excision was associated with
      a higher chance of normal follow-up cervical cytology. CONCLUSIONS: The retrieval
      of endocervical cells was satisfactory following both large loop excision and
      laser cone excision. Laser cone excision is recommended with large or more severe
      lesions.

PMID- 8561001
TI  - Successful conservative treatment of acute uterine inversion in a nulliparous
      woman.

PMID- 8561002
TI  - Spontaneous ovarian hyperstimulation syndrome and hyperprolactinemia in primary
      hypothyroidism.

PMID- 8561003
TI  - Virilizing ovarian leiomyoma: androgen production by lining stromal cells.

PMID- 8561004
TI  - Term delivery after hepatocellular carcinoma resection in previous pregnancy.

PMID- 8561005
TI  - Trisomy 12 mosaicism diagnosed by amniocentesis.

PMID- 8561006
TI  - Conservative versus radical surgery for tubal pregnancy. A review.
AB  - OBJECTIVE: The aim of this work was to analyse the fertility prognosis after
      conservative or radical surgery for tubal pregnancy. DATA SOURCES: Index Medicus
      was searched for all attainable literature on the subject. METHODS OF STUDY
      SELECTION: A total of 40 scientific publications through the latest 40 years were
      selected. For fulfilling the selection criterias the study design should appear
      clearly. Furthermore the rate of women obtaining intrauterine pregnancy and the
      rate of repeat ectopic pregnancy following radical or conservative tubal surgery
      was to be compared using 95% confidence limits. The results from each report were
      compared in four groups according to study design i.e. retrospective non
      comparing materials, retrospective comparing studies, prospective selected
      treatment series or prospective randomized comparing investigations. DATA
      EXTRACTION AND SYNTHESIS: Pooling the results from the retrospective noncomparing
      materials revealed that there was no significant difference in intrauterine
      pregnancy rates, i.e. 46% following conservative tubal surgery and 44% after
      radical surgery. The repeat ectopic pregnancy rate was 10% following conservative
      surgery and 15% after radical surgery. In the group of restrospective comparing
      studies only one of 15 materials could document a significant better intrauterine
      pregnancy rate after conservative tubal surgery than following radical treatment
      for tubal pregnancy. There were no differences either in this group in repeat
      ectopic pregnancy rates. Prospective investigations were almost exclusively
      represented by selected conservative treatment series. In these series the
      average intrauterine pregnancy rate was 57% and the repeat ectopic pregnancy rate
      was 13%. CONCLUSIONS: In studies on fertility after radical or conservative
      surgical treatment for tubal pregnancy no significant difference in intrauterine
      pregnancy rates or repeat ectopic pregnancy rates were found. Prospective
      selected treatment series demonstrated higher intrauterine pregnancy rates than
      retrospective studies. The repeat ectopic pregnancy rate was not raised in
      prospective series. No prospective randomised trial was found.

PMID- 8561007
TI  - Dermatofibrosarcoma protuberans of the vulva: clinico-pathological,
      immunohistochemical and flow cytometric study of a case.

PMID- 8561008
TI  - Induction of labor by PGE2 and other local methods. Physiology, methods and
      guidelines for patient selection.

PMID- 8561009
TI  - Cervical ripening. A rat model for investigation of contractile and passive
      biomechanical properties, with focus on antigestagens, eosinophil granulocytes
      and mast cells.

PMID- 8561010
TI  - Multifetal pregnancy reduction.

PMID- 8561011
TI  - [Cutaneous head and neck carcinoma].

PMID- 8561012
TI  - [Epidemiology of cutaneous head and neck carcinomas].
AB  - Skin Cancer are the more frequent malignant tumors in the caucasian population,
      however significant and particular difference are present in World Cancer
      Registries incidence data. The analysis of the temporal trend, more than the
      geographical trend, is thicken by three characteristics: incidence, relation
      between diagnosis and treatment, register rate. The British Columbia Cancer
      Registry probably gives the more reliable valuation and shows an incidence
      doubled for these tumors during the period of five years considered, (1973-1987).
      These trends are equal in male and female and also in the two type of tumors for
      all sites. The analysis of the Cancer Registries includes Italy as a country with
      an intermediate risk, the relation between male and female and the correlation
      with the age are similar among the Cancer Registries as seen in the caucasian
      population. The analysis of the cut off rate (35-64 years) and cumulative risk (0
      64 years, 0-74 years) shows the importance of the age of insorgence.

PMID- 8561013
TI  - [Etiopathogenesis of cutaneous head and neck carcinomas].

PMID- 8561014
TI  - [Anatomical pathology of cutaneous head and neck carcinomas].
AB  - The author after a short summary about the morphological classification of head
      and neck cutaneous carcinomas, stresses the necessity of a strict interface of
      cooperation between surgeon and pathologist. For a better management of the
      patient with a cutaneous lesions suspected for malignancy is mandatory to take a
      biopsy and to indicate in the histological report the exact diagnosis of
      histotype associated with the morphological features related to prognosis.

PMID- 8561015
TI  - [Cutaneous head and neck carcinomas: biological characteristics, natural history
      and clinical classification].
AB  - In cutaneous carcinoma of the Head and Neck there is a 7% of cases that often
      suffer substantial morbidity and even mortality. The identification of the "high
      risk patient" may derive from the study of the prognostic factors which have been
      published in Literature. The problem has to be differentiated between the basal
      cells carcinoma (BCC) and the squamous cells carcinoma (SCC) due to the locally
      limited aggressiveness of the first and the potential for metastatization of the
      latter. The evaluation of the different variables confirms the inadequacy of the
      present TNM Classification for Cutaneous carcinoma; nevertheless the opportunity
      of a new and omni-comprehensive proposal is questionable.

PMID- 8561016
TI  - [Therapeutic strategies for cutaneous carcinomas in cervical-cortical areas].

PMID- 8561017
TI  - [Lymph node problem in cutaneous head and neck carcinomas].
AB  - Skin carcinomas of the head and neck can produce lymphatic metastases: the main
      lymphatic station of drainage is in the lymph nodes of the parotid region,
      especially for tumours of the upper 2/3 of the face. The analysis of the
      prognostic factors (site of origin, etiology, immunodepression, previous
      treatment, size, thickness, grading, perineural invasion, rapid growth)
      identifies a group of patient at risk, for local recurrence and for lymphatic
      metastases. In those cases, representing less than 10% of these tumours, the
      prophylactic treatment of lymph nodes-parotid and neck nodes-can be reasonable.
      The cases N positive have a severe prognosis, in these patients an aggressive
      surgical treatment, extended to both parotid and neck nodes, followed by
      radiotherapy, is justified. Only prospective studies and statistical evaluation
      of results, could define the real prognostic importance of different factors and
      the best treatment for the lymph nodes.

PMID- 8561018
TI  - [Philosophy in reconstruction of the face].

PMID- 8561019
TI  - [Radiotherapy of cutaneous cervical-facial carcinomas].
AB  - The main goal of therapy for epithelial skin cancer is cure with the best
      functional and cosmetic outcome. Both surgery and radiotherapy give similar
      results for early stage lesions with 5-year local control rates ranging from 85%
      to 95%. Remarkable technological progress has been made yielding well defined
      indications to radiotherapy as a single treatment or in the context of a
      multidisciplinary approach. Selection of treatment should be tailored considering
      anatomic site, surface conformation, size, histology, grading and characteristics
      of tumours (new occurrence, relapse), number of localizations, age and medical
      conditions of the single patient. Surgery, guided by intraoperative control of
      resection margins, is undoubtedly the therapy of choice for most of early stage
      lesions. Radiation therapy plays an important role in specific anatomic
      situations in which the functional or cosmetic result is better than for a
      surgical modality, electively for the treatment of multiple lesions and for large
      deep- infiltrating carcinomas that generally are not suitable to excision.
      Exclusive radiotherapy is also indicated as rescue treatment of surgical relapses
      no more amenable to reexcision as well as for palliation of advanced cases,
      mainly for elderly or medically compromised patients. Postoperative irradiation
      should be considered for macro or microscopic residual disease. Merkel cell or
      adnexal carcinomas and for highly recurrent lesions after repeated surgery.
      Treatment results and complications of radiotherapy are discussed, emphasizing
      high local control rates and good functional and cosmetic outcomes. The main
      irradiation techniques referred to specific anatomic sites are also presented.

PMID- 8561020
TI  - [Cutaneous head and neck carcinomas: personal experience].
AB  - The Authors reviewed the personal surgical series about three hundred ninety-nine
      nonmelanoma skin cancers of the head and neck, examined from 1984 to 1993. The
      commonest histologic types were basal cell carcinoma (BCC) and squamous cell
      carcinoma (SCC). The median age was 70 and 69 years and the male to female ratio
      was 2:1 and 3:1, respectively for BCC and SCC. The distribution of sites of
      origin showed a clear tendency of BCC for arising in the midface region and SCC
      in the auricolar area and the nose. The correlation between local recurrence
      rates and duration of follow-up has proposed again the necessity of a long-term
      observation (over a 5-year period) in order to early detect a relapse or a new
      primary skin cancer. Finally, the Authors examine some clinical factors related
      to a high risk of local recurrence. These variables are: site, size, histologic
      differentiation, stage and previous surgical treatment. The final results are
      comparable to those described in the late Literature.

PMID- 8561021
TI  - [Referential value of auditory threshold depending on age].
AB  - The value of "normal hearing" intended as the "base value of reference" to be
      used also for preventive as well as medical-legal purposes, is still subject of
      study and discussion. The Authors present the results relative to the definition
      of the hearing threshold in a vast "scrupulously screened" group of subjects
      between the ages of 15 and 65 (divided into 10 year bands), resident in
      industrial city areas and made up a homogeneous group of industrial workers with
      the same socioenvironmental characteristics. Distribution is calculated in
      hundreds of values relative to the average bilateral threshold for frequencies
      between 500 and 4000 Hz considering the 90th percentile the reference value.

PMID- 8561022
TI  - [Phonorhinorheometric study and laryngeal sonography in subjects affected by
      velopharyngeal insufficiency].
AB  - The aim of the present study was to evaluate the validity of combining two non
      invasive diagnostic approaches, (photorhinorheometry and sonography) in order
      study phonatory pathology in subjects suffering from velopharyngeal insufficiency
      (VPI). Twenty-six patients with nasal air escape during phonation and/or
      hyperrhinophonia due to to VPI were evaluated employing both methods.
      Phonorhinorheometry permitted air escape through the nasal cavities during
      phonation to be evaluated. Compartmentalization of the pharyngeal and nasal
      resonators during phonation was measured through MCF (maximal consonantic flow)
      values and MCV (mean consonantic volume), both normalized to the intensity of
      sound emission during the consonatic phases of speech. Sonography gave
      information concerning the phonema of resonance and articulation: a modification
      of the method, which also permitted sound production through an electroacoustic
      transductor kept in contact with the prelaryngeal skin, was made. This reduced
      intrinsic noise and increased dynamic modulations of the resonators of the vocal
      tract. Comparison between sonographic recordings obtained through a standard
      microphone and skin transducer permitted evaluation of influence of the vocal
      tract above the glottis on the phonatory process. In particular, recordings had
      by skin transducers showed a wider amplitude display and a better identification
      of vocal attack. Phonorhinorheometry and sonography are useful objective and non
      invasive tools in evaluating phonatory pathology in patients suffering from VPI
      and in monitoring therapeutic approaches.

PMID- 8561023
TI  - [Coronal CT in the indication of the endoscopic surgery of the sinus].
AB  - In this paper the Authors affirm that Functional Endoscopic Sinus Surgery is the
      technique of choice for treatment of nonneoplastic pathologies of paranasal
      sinuses, particularly in chronic infective and polypoid sinusitis. Furthermore,
      they confirm CT scans are mandatory in preoperative planning in order to
      delineate precisely the structures surrounding the surgical field (the lamina
      papyracea and possible dehiscences, the brain, the lacrimal duct, the internal
      carotid artery and the optic nerve), and thereby avoid any possible damage during
      surgery. If endoscopic examination and clinical history suggest a massive
      involvement of ethmoid cavities, both axial and coronal CT scans are necessary.
      Inasmuch as the crucial point in the development of chronic sinus pathology is
      the ostio-meatal complex, the Authors indicate that this structure can be clearly
      identified and studied by means of coronal CT scans, since in this case it is not
      necessary to clarify the depth of the nasal fossae, but, instead, to reveal the
      exact situation and configuration of the two fundamental lamellae, the uncinate
      process and the bulla. These structures lie on a vertical plane and cannot be
      studied with axial CT scans without reviewing several series scans made in close
      proximity, which increases the patient's exposure to x-rays as well as the
      expense of the study. This paper is an attempt to shorten and rationalize routine
      radiologic procedures when a limited ethmoid involvement, previously detected by
      careful endoscopic examination, is under investigation.

PMID- 8561024
TI  - [Comparative study of most recent surgical techniques for the treatment of the
      hypertrophy of inferior turbinates].
AB  - The choice among the several techniques carried out to treat the hypertrophy of
      inferior turbinates is still difficult and matter of great interest. In the
      present study the Authors evaluated the efficacy and sequelae of the most common
      operations suitable for this pathology. The surgical procedures taken into
      consideration were (1) electrocautery; (2) cryotheraphy; (3) lasertherapy; (4)
      submucosal decongestion without lateral outfracture; (5) sub-mucosal decongestion
      with lateral outfracture; (6) turbinectomy. The six groups of patients (total
      382) have been followed up for 4 years after surgery. At this aim the
      rhinomanometry, acoustic rhinometry, MCTt and SIgA dosage have been checked up
      together with the symptomatologic score. The conclusion was that the submucosal
      decongestion with lateral outfracture was the most effective technique for the
      chronic nasal obstruction, able to respect all the nasal functions.

PMID- 8561025
TI  - [Rhinocerebral mucormycosis: a case report].
AB  - The Authors report a case history of rhinocerebral mucormycosis in a patient with
      chronic lymphatic leukaemia and recommend that therapy be based on three
      different approaches: treatment for the underlying disease, systematic antifungal
      treatment with Amphotericine B, and surgical asportation of diseased tissue. They
      affirm that results may be surprisingly successful, even in cases with signs of
      orbital-cerebral involvement which are indicative of a poor prognosis and the
      concomitant presence of a serous disease such as leukaemia.

PMID- 8561026
TI  - [The illness of Sigmund Freud].

PMID- 8561027
TI  - [The treatment of allergic vasomotor rhinitis: diagnostic problems and local
      immunotherapy].
AB  - Treatment of allergic vasomotor rhinitis is to be regarded with the factors that
      modify the symptomatology. In fact must be considered the morphological changes
      (septum deviation, adenoids, turbinates hypertrophy, polyps) infections
      (bacteria, chlamydiae, micetes) and specific allergens. Identification of
      allergens and sensitization threshold is to be studied; then specific
      hyposensitization will be assessed. In the present study, 68 subjects having
      nasal reactivity have been observed and underwent to different ways of treatment:
      18 with permanent stenosis identified by rhinomanometry and not modified with
      vasoconstrictors were operated; 25 of the 50 patients with normal nasal cavities
      showed contemporary infections: after a specific antimicrobic or antimycotic
      treatment, a clear improvement was obtained documented by rhinomanometry before
      and after nasal stimulations. The 50 patients with normal morphology underwent a
      local hyposensitization against the allergens. As a matter of fact: a) in all
      cases a clear improvement was obtained in phase of increasing; b) after one year
      of maintainance just 13 over 50 (26%) returned to previous conditions. The
      Authors remark how local immunotherapy by the nasal way give good possibilities
      in a high percentage of cases in the following conditions: correct clinical
      evaluation, especially concerning the identification of factors determining
      vasomotor rhinitis; employment of precise techniques for diagnosis; observation
      of clinical data and results turning out from instrumental investigations,
      especially concerning the nasal provocation test evaluated by rhinomanometry.

PMID- 8561028
TI  - A clonal translocation t(10;21) in an optic glioma of a patient with
      neurofibromatosis type 1 (NF 1).
AB  - An 11-year-old boy affected by neurofibromatosis type 1 is presented with
      severely impaired vision on the right eye (0.1). MRI demonstrated a 2.3 x 1.8 cm
      tumour of the optic chiasma. After open biopsy cytogenetic analysis was performed
      on primary cultures of this optic glioma (grade I). A clonal translocation
      t(10;21)(q21.2;21.1) was detected in 66% of the metaphases analysed. The boy
      received fractioned irradiation with a total tumour dose of 60 Gy. The ultimate
      MRI taken 18 months after radiotherapy showed no residual tumour. The vision on
      the right improved to 0.2, but decreased on the left to 0.6. The patient attends
      high school with no impairment in his daily life.

PMID- 8561030
TI  - Approach through the temporal horn of the lateral ventricle for clipping of large
      dorsal type basilar bifurcation aneurysms.
AB  - The authors describe an approach through the temporal horn of the lateral
      ventricle which proved to be useful for clipping of a large dorsal type basilar
      bifurcation aneurysms. It facilitates the preservation of the perforating
      arteries behind the aneurysm, because it gives sufficient working space to move
      the aneurysm dome. Furthermore this approach avoids many of the disadvantages of
      other approaches, especially the risk of iatrogenic injuries of the Sylvian or
      Labe's vein.

PMID- 8561029
TI  - Does a routine operation for intracranial aneurysm incur brain damage?
AB  - A biochemical marker of brain cell damage, the BB-isozyme of the intracellular
      enzyme Creatine Kinase (CK), was used to evaluate any possible injury to the
      brain, caused by an operation for a ruptured intracranial aneurysm (SAH). CSF-CK
      BB was assessed before and at intervals after operation in a series of 60
      patients, aged 29-71 (mean 51 years) operated on for intracranial aneurysms, all
      but one after SAH. The m/f ratio was 18/42. 35 of the 60 patients were operated
      on acutely, i.e. within 72 hours after the SAH. CK BB was determined as CKB
      activity after immunological inactivation of CKM. Normally there should be almost
      no detectable enzyme activity in the CSF. The pre-operative CK BB-activity was
      0.01+ -0.01 mikrokatal in the patients in Hunt & Hess grade I who were operated
      on > 7 days after their SAH, and 0.05+ -0.04 in those operated on acutely,
      probably still reflecting the effects of the SAH on the brain. The mean per
      operative CK BB increase was 0.11+ -0.17 for patients who had an uneventful
      postoperative course, compared to 0.39+ -0.49 for those showing some degree of
      immediate postoperative deterioration. This difference is significant at the 1%
      level. 52 of the 60 patients showed a rise of CK BB after operation. The mean
      increase for those patients operated upon in a good state and without any
      complication or postoperative deterioration was 0.02+ -0.03 mikrokatal, which
      could therefore be considered as a "normal" or acceptable elevation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8561031
TI  - Parkinsonism and rest tremor secondary to supratentorial tumours sparing the
      basal ganglia.
AB  - Intracranial neoplasms are an uncommon cause of symptomatic Parkinsonism and rest
      tremor. We found an incidence of 0.3% in a prospective evaluation of 907 patients
      with supratentorial tumours. Eight patients with Parkinsonism and rest tremor
      secondary to supratentorial tumours sparing the basal ganglia are reported. Neuro
      imaging revealed compression and distortion of the basal ganglia by large tumours
      which were identified histopathologically as meningiomas in four patients and as
      an epidermoid, a fibrillary astrocytoma, an anaplastic oligodendroglioma and a
      glioblastoma. Six patients underwent tumour removal by craniotomy, in two the
      histopathology was obtained by stereotactic biopsy. Four patients were free of
      Parkinsonian symptoms and signs on long-term follow-up. The possible
      pathophysiological mechanisms involved are discussed. Since some of these
      patients closely resemble cases of idiopathic Parkinson's disease, and the
      movement disorder can precede other symptoms and signs or will remain isolated in
      the further course, the diagnosis of an intracranial neoplasm was generally
      delayed in these patients. Increased awareness of this rare entity may lead to an
      earlier diagnosis. Early computed tomography in patients with Parkinsonism might
      help to detect these patients with a potentially curable cause of their
      condition.

PMID- 8561032
TI  - Patient attitudes to myelography, computed tomography and magnetic resonance
      imaging when examined for suspected lumbar disc herniation.
AB  - In reports of diagnostic methods in disorders of the spine focus is centred on
      diagnostic resolution, while psychological effects and patients' discomfort are
      often disregarded. To get a comprehensive picture of the appropriateness of a new
      technology the latter factors need to be explored and included in an assessment.
      In a prospective study, eight patients with signs of lumbar disc herniation
      underwent myelography, computed tomography and magnetic resonance imaging. A
      structured patient interview on attitudes to these technologies was carried out
      after all three examinations had been carried out. Myelography was most often
      reported painful and unpleasant among the three modalities. Discomfort due to
      magnetic resonance imaging stem from the narrow calibre of the machine and the
      noise. In computed tomography immobilization was the main reason for discomfort.
      Altogether most patients preferred computed tomography. In view of the fact that
      myelography must be considered as diagnostically inferior to the other two
      examinations, the reported discomfort from myelography indicates that computed
      tomography and magnetic resonance imaging should be the primary examinations for
      patients with lumbar disc herniation.

PMID- 8561033
TI  - Chordoma and chondrosarcoma: relationship to the internal carotid artery.
AB  - In 6 patients with chordoma and 1 patient with a chondrosarcoma in the
      petroclival region, the internal carotid artery (ICA) showed a rather interesting
      relationship. The striking finding was the marked anterior (ventral) displacement
      of the adjacent segments of the ICA by the tumour. Complete encasement of the
      artery was not seen despite the massive size of the tumour. Narrowing of the
      caliber of ICA was seen in 1 case. The displacement of the ICA pointed toward the
      origin of the tumour and the pattern of its spread suggested pre-operatively the
      pathological diagnosis. Pre-operative recognition of the carotid artery neoplasm
      relation helped to better protect the ICA during surgery on these formidable
      lesions.

PMID- 8561034
TI  - Multiple pyogenic brain abscesses.
AB  - Thirty eight patients with multiple pyogenic brain abscesses constituted 11% of
      all the brain abscesses treated during a 12 year period. Sixty per cent (23) of
      the patients were in the first two decades of life, including 9 (24%) infants.
      The clinical presentation was similar to brain abscess in general. 21 patients
      had altered "sensorium" at the time of admission. Otogenic brain abscesses were
      the commonest (26%), followed by those associated with congenital cyanotic heart
      disease (18%). The abscesses were invariably large in size. The pus was sterile
      on culture in 11 (29%) patients, while Staphylococcus aureus was the commonest
      organism grown in 9 (24%) patients. Aspiration of the pus was required as a life
      saving measure, to control raised intracranial pressure, in 29 (76%) patients.
      Twelve (32%) of these patients underwent secondary excision of the abscess
      capsule. The overall mortality was 32% with failure to control intracranial and
      systemic infection as the major causes of mortality. Level of consciousness at
      the time of admission was the most significant factor affecting the outcome.
      Surgery has a definite therapeutic and life saving role in the management of
      multiple pyogenic brain abscesses. A systematic treatment plan for multiple
      abscesses is proposed.

PMID- 8561035
TI  - Seizure control and extent of mesial temporal resection.
AB  - Controversy exists about the extent of mesial temporal lobe resection that
      improves seizure control in patients with temporal lobe epilepsy. In this
      retrospective study, 70 patients with mesial temporal seizure activity (without
      evidence of tumor or vascular malformation) were surgically treated and followed
      for at least 2 years. The extent of mesial temporal resection was based on the
      findings of interictal and ictal discharges using depth electrodes, which were
      inserted preoperatively or intraoperatively by the orthogonal approach to the
      amygdaloid and hippocampal regions. Only the amygdala was resected along with the
      limited lateral neocortex if no epileptiform activity involved the hippocampus.
      The amount of hippocampal excision was determined by the extent of interictal
      seizure activity. The following groups became seizure free: all 8 patients with
      only amygdalar resection; 6 of 10 patients with amygdalar and < or = 1 cm
      hippocampal resection; 23 of 38 with 1-2 cm hippocampal removal, and 11 of 14
      with > 2 cm hippocampal excision. In cases where there was no hippocampal
      resection, neuropsychological outcome compared favorably with controls. Our
      results suggest that although most patients with temporal lobe epilepsy require
      hippocampal resection of varying degrees, there is a subset in whom the amygdala
      may be the crucial element of a mesial temporal epileptogenic network. These
      patients can undergo a surgical resection sparing the hippocampus without
      compromising seizure outcome.

PMID- 8561036
TI  - Extradural haematomas: how many deaths can be avoided? Protocol for early
      detection of haematoma in minor head injuries.
AB  - Since 1988 in the referral area of the Neurosurgical Unit of Cesena, Italy, a
      protocol for prevention of deterioration in minor head injury was adopted. Adult
      patients admitted to any hospital with a GCS score of 15 and 14 (transient)
      without neurological deficit are submitted to skull x-ray: if a fracture is
      present the patient is sent for CT to the nearest regional Center. In children
      skull x-ray is not routinely performed and the patients are admitted for
      observation to the nearest regional hospital. To assess the effects of such a
      protocol on morbidity and mortality of extradural haematoma (EDH), from June 1989
      to September 1991 a consecutive series of 95 patients harbouring a significant
      acute EDH was collected. Mean age was 31 years; in 70% trauma was caused by a
      road traffic accident. The patients were divided into 3 categories: a) Clinical
      deterioration: mean GCS at surgery was 7.7; out of 27 patients, 12 had anysocoria
      and 3 bilaterally fixed pupils; the outcome showed only two deaths, one related
      to the EDH and the other to cardiac arrythmia. Most of the patients deteriorated
      either during transport after being recognized as at risk or already in
      Neurosurgery allowing rapid surgical treatment. b) Impaired consciousness (18
      cases) and c) Minor head injury (50 cases) are groups of patients treated without
      morbidity and mortality. If we compare these results with those of a previous
      study of our group done in 1980-86, there is a statistically significant
      difference concerning both mortality and morbidity. Our protocol proved therefore
      to be adequate in preventing most deaths that occurred following clinical
      deterioration in an apparently low risk patient.

PMID- 8561038
TI  - Glasgow Coma Scale and brain death--a proposal.

PMID- 8561037
TI  - Head-injured adult patients with GCS of 3 on admission--who have a chance to
      survive?
AB  - The authors analysed a series of 111 adult patients admitted to the Department of
      Neurosurgery, Medical University of Lodz directly after trauma with initial GCS
      of 3 points. 74% of them had intracranial haematoma, mainly subdural, and were
      treated surgically within the first 3 hours after trauma. 8 patients had no
      abnormalities on CT scans. 99 (89%) patients died 2 to 30 days after injury, 8
      (7%) survived in a vegetative state, and only in 4 (4%) was a satisfactory result
      noted, but 2 of them had a stable neurological deficit. 3 of these 4 patients had
      epidural haematomas and 1 had not abnormalities on repeated CT examinations. We
      conclude, that among patients with GCS of 3 on admission, only those without
      major CT abnormalities or with epidural haematoma have a chance of survival.
      Cases with cerebral lesions on the initial CT examination have an invariably bad
      prognosis. They could be taken into account as a potential organ donor from the
      very moment of admission, but only after cerebral circulatory arrest occurred and
      brain death has been proved according to internationally accepted standards.

PMID- 8561039
TI  - Transplantation of cultured sympathetic ganglionic neurons into parkinsonian rat
      brain: survival and function of graft.
AB  - The superior cervical ganglia (SCG) of newborn rats, which had been cultured as
      explants for varying periods of time, were transplanted into the striatum of rats
      with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway
      to examine the survival and functional properties of the sympathetic neurons
      maintained in long-term culture prior to grafting. In the rats given the SCG
      cultured in vitro for 2 weeks, apomorphine-induced rotational behaviour was
      satisfactory reduced. The rats receiving the SCG from 4-week-old cultures showed
      only modest behavioural changes. The grafting of the SCG cultured for 6 weeks in
      vitro did not affect the rotational behaviour. These behavioural data
      corresponded with the histological assessment of the graft survival by use of
      catecholamine histofluorescence. The present results suggest the critical time
      period in vitro which might allow the cultured sympathetic neurons to be
      successfully grafted.

PMID- 8561040
TI  - Transplantation of basal forebrain cells of foetal rats into the subarachnoid
      space: improvement of disturbance of passive avoidance memory due to injury of
      nucleus basalis magnocellularis.
AB  - Basal forebrain cells of foetal rats were transplanted into the subarachnoid
      space of adult rats harbouring a kainic acid-induced unilateral lesion in the
      nucleus basalis magnocellularis. Passive avoidance response tests were performed
      eight weeks after the transplantation, and the results were compared with those
      of lesioned but non-transplanted rats and of non-lesioned control rats. Although
      acquisition impairments did not improve, retention impairments were significantly
      ameliorated in the transplanted rats. Histologically, transplanted foetal neurons
      survived and grew very well over the cortical surface, and exhibited facilitated
      neuritic elongation on acetylcholinesterase staining. Choline acetyl-transferase
      immunoreactive neurons were found along the needle track as well as in the
      subarachnoid graft tissues. The results seem to indicate that not the re
      innervation from the graft to the host cortex but the diffusional supply of
      neurotransmitters and/or their synthetic enzymes and neurotrophic factors were
      responsible for improvement of memory deficits. The subarachnoid space proved to
      be an adequate place for growth of transplanted neuronal and glial cells for
      reasons of ample supply of oxygen and nutrition and of low tissue pressure.

PMID- 8561041
TI  - Cross-sectional areas of lumbar muscles after surgical treatment of lumbar disc
      herniation. A study with magnetic resonance imaging after microdiscectomy or
      percutaneous nucleotomy.
AB  - We assessed in this study the potential development of postoperative muscle
      atrophy in the operation area in 39 patients treated by either microdiscectomy or
      percutaneous nucleotomy for lumbar disc herniation. The cross-sectional areas of
      the lumbar muscles were measured on magnetic resonance images created on the day
      preceding the operation and 6 months postoperatively. The cross-sections of the
      lumbar muscles remained unchanged during the observation period in all treated
      patients indicating that no muscle atrophy had developed in the operation area.
      Since peroperative tissue trauma may correlate with subsequent muscle denervation
      and atrophy, this finding may be due to the tissue sparing nature of
      microdiscectomy and percutaneous nucleotomy, thus encouraging the use of these
      techniques in the treatment of lumbar disc herniation.

PMID- 8561043
TI  - Transcranial Doppler sonography in experimental Cushing response.
AB  - Searching for the early warning symptoms of brain ischaemia, transcranial Doppler
      sonography (TCD) was used in cats during the Cushing response. The study was
      performed on seven cats. The intracranial pressure was increased by means of
      different rate lumbar infusions. The TCD changes of middle cerebral artery (MCA)
      and basilar artery (BA) flows were analyzed at the stage of the slightest but
      significant systemic blood pressure increase. The first symptoms of Cushing
      phenomenon were accompanied by BA flow pattern alternations while the MCA flow
      remained unchanged. The study suggests the necessity of BA TCD monitoring in
      cases at risk from brain stem ischaemia. It was shown also that in such cases the
      MCA TCD study can be misleading.

PMID- 8561042
TI  - Efficacy of high dose amino acid solution on spinal cord injury induced by focal
      Nd:YAG laser irradiation.
AB  - In this experimental study, a neodymium:yttrium-aluminium-garnet (Nd:YAG) laser
      was used to induce highly reproducible focal spinal cord lesions in anaesthetized
      guinea pigs. The efficacy of high dose amino acid solution (HDAAS) on this injury
      is investigated. Experiments were performed on 36 animals divided into three
      groups; sham operated controls, laser irradiated surgical controls, and amino
      acid groups. Acute responses to injury were evaluated with somatosensory (SSEP)
      and motor evoked potentials (MEP) and functional recovery was assessed for 8
      weeks using the inclined plane technique. In the laser irradiated surgical
      control group, MEP disappeared one hour after the laser injury, but SSEP revealed
      changes of amplitude and latency. In this group, the average value of the
      inclined plane at 24 hours after the laser application was 45.3 +/- 1.4 degrees.
      In the amino acid group, at the sixth hour of injury, MEP and SSEP changes
      improved with infusion of HDAAS for 4 hours. This improvement was statistically
      significant (for latency of SSEP U = 140 p < 0.05). Inclined plane value at 24
      hours after the laser application was 65.5 +/- 1.2 degrees in this group. This
      study showed that application of Nd:YAG laser irradiation on the spinal cord
      induced spinal cord injury which presented as paraparesis, HDAAS may provide
      significant therapeutic protection in secondary damage following this injury and
      may have a potential role in the treatment of acute spinal cord injury.

PMID- 8561044
TI  - Transcranial cerebral oximetry and carotid cavernous fistula occlusion. Technical
      note.
AB  - Different methods have been used in the evaluation and monitoring of the cerebral
      oxygen supply during neuro-interventional therapies. Attenuation of near-infrared
      light by the chromophores oxyhemoglobin and deoxyhemoglobin have shown to be
      useful in the study of the cellular oxygen metabolism and oxygen delivery to the
      brain. Transcranial cerebral oximetry (TCCO) has the advantage of providing real
      time information regarding regional brain oxygen saturation (rSO2) by using
      wavelengths in the near-infrared range. We present a patient with a carotid
      cavernous fistula who underwent balloon occlusion and concurrent continuous TCCO
      monitoring. TCCO was found to be a useful tool providing immediate rSO2 values
      during the angiographic and interventional procedures. Initial balloon occlusion
      of a carotid cavernous fistula resulted in partial occlusion of the internal
      carotid artery lumen causing an immediate decrease in rSO2 which correlated with
      angiographic findings. Subsequent reocclusion of the fistula produced a slower
      and smaller degree of decrease in rSO2 with clinical improvement in the patient.
      Changes in rSO2 were detected before any adverse clinical event was observed.
      TCCO was reliable, safe, sensitive, and provided a real-time assessment tool for
      the monitoring of brain oxygen supply in a patient undergoing a neuroendovascular
      procedure.

PMID- 8561045
TI  - Enhanced magnetic resonance imaging of the rat brain using a stereotactic device
      with a small head coil: technical note.
AB  - A stereotactic device (SDM) was developed for performing consistent magnetic
      resonance imaging (MRI) of the rat brain. The SDM was developed by adapting a
      radiofrequency transmit/receive head coil of 4.4 cm inner diameter (quadrature
      birdcage head coil), and utilizing partial acrylic construction for the
      positioning elements. The small head coil provides improved resolution and
      accuracy of the image, while the stereotactic holder permits repeatable and
      accurate imaging of identified brain structures. This system provides several
      advantages over existing experimental MRI devices. The SDM ensures that the head
      is always placed in the center of the coil in a uniform fashion. Standardized
      positioning of the skull optimizes image quality and provides a consistent
      orientation of the brain. In addition, a widely-utilized coordinate system
      described by Paxinos and Watson can be employed to assist in the identification
      of structures and to facilitate surgical planning. The SDM is compatible with a
      recently-developed stereotactic device for radiosurgery with the Gamma Knife,
      thus permitting the planning and performance of experimental radiosurgery using
      the same coordinate system. The SDM also provides the ability to perform MRI and
      radiosurgery at different times, thus avoiding the need for prolonged anesthesia
      during an experimental study. Finally, the SDM allows repeated MRI of the same,
      identifiable positions in the brain during longitudinal experimental studies. The
      utility of this device is demonstrated here by examining the time course of
      cerebral damage that evolved within a radiosurgical focus after gamma
      irradiation.

PMID- 8561046
TI  - Transcranial Doppler penetrance of methyl methacrylate: technical note.
AB  - Methyl methacrylate is often used in cranioplasties and reconstructions of
      crainiectomies at sites through which transcranial Doppler (TCD) examinations are
      performed for assessment of cerebral hemodynamics. To assess the penetrance of
      methyl methacrylate by a transcranial Doppler ultrasound beam, methyl
      methacrylate discs of thickness from 4 to 10 mm were constructed and placed in
      the path of the ultrasound beam during routine-insonation of the middle cerebral
      artery and femoral artery in a healthy volunteer. The quality of ultrasound
      signals obtainable markedly deteriorated as thicker discs were used, and was
      almost completely absent at a thickness of 10 mm. The impairment of ultrasound
      transmission at frequencies used for transcranial Doppler ultrasound by methyl
      methacrylate is significant and represents a limitation in TCD studies that
      should be recognized by the clinician.

PMID- 8561047
TI  - Giant central neurocytoma with tetraventricular and extra-axial extension. Case
      report.
AB  - The central neurocytoma is a recently recognized benign intraventricular tumour
      of young adults. The authors report a unique case of a panventricular neurocytoma
      with extension to the interpeduncular and prepontique cisterns which developed in
      a 35-year-old woman with a 7-year history of headaches and amenorrhea. They
      review the different pathological and topographical patterns of previously
      published neurocytomas and discuss the histogenesis of this rare tumour.

PMID- 8561048
TI  - Normal testicular descent and the aetiology of cryptorchidism.

PMID- 8561049
TI  - Hemocyanins.

PMID- 8561050
TI  - Enthalpic contribution to protein stability: insights from atom-based
      calculations and statistical mechanics.

PMID- 8561051
TI  - Energetics of protein structure.

PMID- 8561052
TI  - Molten globule and protein folding.

PMID- 8561053
TI  - Utility of creatinine excretion in body-composition studies of healthy men and
      women older than 60 y.
AB  - This study evaluated whether aging alters the usefulness of creatinine excretion
      as an index of lean body mass (LBM) or muscle mass in healthy men and women.
      Creatinine excretion was determined while 24 young (15 men and 9 women aged < 32
      y) and 38 older (23 men and 15 women aged > 60 y) healthy volunteers stayed at a
      clinical research center for 3 d. Total LBM was determined by 40K counting in all
      subjects, and cross-sectional areas of upper arm and thigh muscles were
      determined in some subjects (10 young, 20 old) by magnetic resonance imaging. The
      slopes and intercepts of the regression equations relating LBM to average daily
      creatinine excretion were the same in the younger and older groups, and the
      precision with which LBM could be determined from creatinine excretion was not
      diminished by aging. Creatinine excretion was closely correlated with cross
      sectional areas of upper arm (r = 0.85) and thigh (r = 0.88) muscles, and the
      slopes and intercepts of the regression equations were not significantly affected
      by age. The older group had a mean LBM smaller than that of the younger group,
      which was accounted for entirely by a smaller muscle mass. Mean resting metabolic
      rate (RMR), whole-body protein turnover rate, and thigh strength were lower in
      the older group than in the young group. Adjustment of RMR and protein turnover
      for creatinine excretion or LBM eliminated the age effects. Strength was lower in
      the older group even after adjustment for creatinine excretion or LBM. This study
      indicates that creatinine excretion is useful for evaluating body composition in
      both young and old subjects.

PMID- 8561054
TI  - Evaluation of dual-energy X-ray absorptiometry for body-composition assessment in
      piglets and term human neonates.
AB  - The reproducibility, accuracy, and precision of dual-energy X-ray absorptiometry
      (DXA) was assessed by scanning 13 piglets (1471-5507 g) in triplicate. In four
      piglets, fat content was increased with porcine lard around the abdomen;
      additional measurements were performed on these animals. Reproducibility in DXA
      measurements from the animals without added fat was 0.09% for body weight, 1.95%
      for bone mineral content (BMC), and 5.35% for fat content. DXA estimates of body
      weight, BMC, and fat content were significantly correlated with scale body
      weight, ash weight, chemical calcium, and chemical fat. Body weight was measured
      accurately but fat content was overestimated by DXA. Mean BMC estimated by DXA
      represented 48% of ash weight and 215% of calcium content. The precision of DXA
      was 0.23% for body weight, 10.99% for ash weight, and 4.44% for calcium content.
      The precision of DXA for fat content was poor. However, for measurements
      performed in piglets with > 250 g fat, the precision was 8.85%. Thirty
      appropriate-forgestational-age term human neonates (birth weight: 3188 +/- 217 g)
      were scanned once during the first week of life. BMC and fat content were 54 +/-
      6 and 470 +/- 92 g, respectively, which corresponded to 26.4 +/- 2.6 g calcium
      and 427 +/- 82 g fat. These were close to the reference values previously
      determined by chemical analysis. This study suggests that DXA is accurate and
      reliable for measurement of calcium and fat contents in human neonates. Further
      refinements would be beneficial for determining fat content in preterm human
      infants.

PMID- 8561055
TI  - Measuring the thermic effect of food.
AB  - The thermic effect of food (TEF), defined as the increase in metabolic rate after
      ingestion of a meal, has been studied extensively, but its role in body weight
      regulation is controversial. We analyzed 131 TEF tests from a wide range of
      subjects ingesting meals of varying sizes and compositions. Each test lasted 6 h.
      Of the total 6-h TEF, 60% of the total had been measured after 3 h. 78% after 4
      h, and 91% after 5 h. We developed a three-parameter curve to fit the data, which
      reduced noise and gave additional information about the TEF. The area under this
      parametric curve was positively correlated with fat-free mass (FFM) and meal size
      (MS) and negatively correlated with meal size squared (MS2) with an R2 of 0.35.
      The usual area under a curve created by connecting the data points of a line was
      correlated with the same factors but with an R2 of 0.28. The peak of the
      parametric curve was positively correlated with FFM and MS and negatively
      correlated with MS2, percent body fat, and meal composition. The time at which
      the peak occurred correlated positively with MS and percent fat in the meal. Our
      analysis suggests that an inadequate measurement duration of the TEF could lead
      to errors. In general, we recommend that the TEF be measured for > or = 5 h.

PMID- 8561056
TI  - Reduced stomach capacity in obese subjects after dieting.
AB  - The objective of the study was to assess the change in gastric capacity of obese
      subjects consuming a hypoenergetic diet. Otherwise healthy, obese subjects
      participated in a prospective controlled study as hospital outpatients. Fourteen
      (11 females, 3 males) subjects were assigned to the diet group and 9 (7 females,
      2 males) were assigned to the control group. Subjects in the diet group were
      provided a 2508-kJ/d(600 kcal/d) formula diet for 4 wk. Subjects in the control
      group ate ad libitum for 4 wk. Gastric capacity was determined before the study
      and 4 wk later by oral insertion of a latex gastric balloon after an overnight
      fast. The balloon was infused with water at a rate of 100 mL/min, with pauses for
      measuring intragastric pressure, until no further distension was tolerated. Two
      indexes for estimating gastric capacity were used based on subjective and
      objective criteria: 1) the maximal volume that could be tolerated, and 2) the
      volume required to produce a rise in water pressure of 5 cm. Subjects in the diet
      group, who lost a mean of 9.1 kg, showed a 27% reduction in gastric capacity
      based on the first index (P = 0.004) and a 36% reduction based on the second
      index (P = 0.006). For the control subjects, gastric capacity did not change
      significantly with use of either index. The results demonstrate a reduction in
      gastric capacity in obese subjects after a restricted diet.

PMID- 8561057
TI  - Similar weight loss with low- or high-carbohydrate diets.
AB  - The goal of this study was to evaluate the effect of diets that were equally low
      in energy but widely different in relative amounts of fat and carbohydrate on
      body weight during a 6-wk period of hospitalization. Consequently, 43 adult,
      obese persons were randomly assigned to receive diets containing 4.2 MJ/d (1000
      kcal/d) composed of either 32% protein, 15% carbohydrate, and 53% fat, or 29%
      protein, 45% carbohydrate, and 26% fat. There was no significant difference in
      the amount of weight loss in response to diets containing either 15% (8.9 +/- 0.6
      kg) or 45% (7.5 +/- 0.5 kg) carbohydrate. Furthermore, significant decreases in
      total body fat and waist-to-hip circumference were seen in both groups, and the
      magnitude of the changes did not vary as a function of diet composition. Fasting
      plasma glucose, insulin, cholesterol, and triacylglycerol concentrations
      decreased significantly in patients eating low-energy diets that contained 15%
      carbohydrate, but neither plasma insulin nor triacylglycerol concentrations fell
      significantly in response to the higher-carbohydrate diet. The results of this
      study showed that it was energy intake, not nutrient composition, that determined
      weight loss in response to low-energy diets over a short time period.

PMID- 8561058
TI  - Serum transferrin and ferritin in pubertal boys: relations to body growth,
      pubertal stage, erythropoiesis, and iron deficiency.
AB  - We studied serum transferrin and ferritin concentrations in relation to
      individual body growth, stage of puberty, blood hemoglobin, and red blood cell
      iron (RBCI) in 60 prepubertal or early pubertal boys at 3-mo intervals for 18 mo.
      One-third of the boys had increased serum transferrin concentrations and almost
      all had decreased ferritin concentrations during the followup. No change in mean
      transferrin was observed but the individual 18-mo increments in transferrin
      correlated positively with the increments in hemoglobin (r = 0.55, P < 0.001) and
      in estimated RBCI (r = 0.31, P = 0.02). Serum transferrin remained stable at
      different genital stages, but ferritin was lower in the pubertal than in the
      prepubertal boys. Transferrin concentrations at 18 mo correlated positively with
      the preceding weight velocities. The rise in transferrin did not lead to an
      increase in iron-deficiency anemia. In contrast, transferrin rose in boys whose
      hemoglobin increased. In pubertal boys with relatively ample iron status, serum
      transferrin may be an indicator of increased availability of iron for
      erythropoiesis. The declining ferritin concentration indicates that part of the
      extra iron is mobilized through redistribution from stores to red blood cell mass
      and is generally associated with greatly increasing absorption. Thus, the
      pubertal changes in transferrin and ferritin are not necessarily indications of
      iron deficiency.

PMID- 8561059
TI  - Effects of interaction of RRR-alpha-tocopheryl acetate and fish oil on low
      density-lipoprotein oxidation in postmenopausal women with and without hormone
      replacement therapy.
AB  - We evaluated the effects of RRR-alpha-tocpheryl acetate (alpha-tocopheryl
      acetate) and hormone-replacement therapy (HRT) on the oxidative susceptibility of
      low-density lipoprotein (LDL) in postmenopausal women consuming a fish oil
      supplement. The independent effect of fish oil was also assessed. Forty-eight
      women, equally divided between women using and not using HRT, participated in a
      double-blind crossover trial. Each of the four periods lasted 5 wk and was
      followed by a 4-wk washout interval. During each period all subjects were given a
      15-g supplement of fish oil and either 0 (placebo), 100, 200, or 400 mg alpha
      tocopheryl acetate daily. LDL resistance to oxidative modification was assessed
      by calculating lag time, propagation rate, and maximum production of conjugated
      dienes. Supplementation with fish oil and placebo shortened lag time and slowed
      propagation rate in women both using and not using HRT. After subjects consumed
      fish oil, supplementation with alpha-tocopheryl acetate increased plasma and LDL
      alpha-tocopherol contents significantly and lengthened lag time (at even the
      lowest concentration) but had no significant effect on propagation rate or
      maximum production compared with values measured after consumption of fish oil
      alone. Women not using HRT had faster propagation rates and higher maximum
      production than women using HRT; after supplementation with fish oil and alpha
      tocopheryl acetate these differences prevailed. Supplements as low as 100 mg
      alpha-tocopheryl acetate/d increase the resistance of LDL to oxidation when fish
      oil supplements are used. HRT and fish oil supplements may independently affect
      LDL oxidative susceptibility.

PMID- 8561060
TI  - Kinetics of total plasma homocysteine in subjects with hyperhomocysteinemia due
      to folate or cobalamin deficiency.
AB  - Hyperhomocysteinemia in cobalamin and folate deficiency reflects an imbalance
      between influx and elimination of homocysteine (Hcy) in plasma. We investigated
      the kinetics of total Hcy (tHcy) in plasma after peroral Hcy administration in 19
      volunteers with hyperhomocysteinemia (mean +/- SD: 67.1 +/- 39.5 mumol/L; range:
      23.5-142.8 mumol/L) before and after supplementation with cobalamin and/or
      folate. Vitamin therapy decreased plasma tHcy to 21.8 +/- 14.1 mumol/L (range:
      9.6-57.9 mumol/L) but caused only a marginal decline in the area under the curve
      (AUC) by 8% and plasma half-life by 21%. Using the equations for steady-state
      kinetics, these data indicate that mean plasma tHcy clearance is normal and that
      massive export of Hcy from tissues into plasma is the major cause of
      hyperhomocysteinemia in cobalamin or folate deficiency. However, the spread in
      AUC and plasma half-life values was large in hyperhomocysteinemia subjects,
      suggesting marked individual variability in tHcy clearance. Plasma methionine
      after Hcy loading did not increase before (0.9 +/- 6.8 mumol/L) but increased
      normally (12.8 +/- 4.6 mumol/L) after vitamin therapy, and the methionine
      response discriminated between vitamin-deficient and vitamin-replete subjects. In
      cobalamin- or folate-deficient subjects, only 6.5 +/- 3.0% of the Hcy dose was
      excreted unchanged in the urine, demonstrating that urinary Hcy excretion does
      not explain normal tHcy plasma clearance in subjects with impaired Hcy
      remethylation. Our data suggest that hyperhomocysteinemia in folate and cobalamin
      deficiency is related to increased influx of Hcy to plasma, and that the
      methionine synthase function is not an important determinant of elimination of
      Hcy from plasma. The large interindividual difference in Hcy clearance may be
      explained by variable adaptation to impaired methionine synthase function through
      increased Hcy flux through alternate metabolic pathways.

PMID- 8561061
TI  - The influence of different protein sources on phytate inhibition of nonheme-iron
      absorption in humans.
AB  - The inhibiting effect of phytate on nonheme-iron absorption from different
      protein sources was examined in human subjects using extrinsic radioiron
      labeling. A drink containing maltodextrose and corn oil was used as a control
      meal to which was added sufficient sodium phytate to provide 300 mg phytic acid
      and/or various protein sources. The proteins were selected to cover a broad range
      of effects on bioavailability and included egg white, meat, and phytate-free soy
      protein. When sodium phytate alone was added, there was a pronounced 83-90%
      reduction in mean absorption in separate studies with a composite average decline
      of 86%. Despite a wide range in absorption from meals containing the three
      protein sources, a remarkably similar relative inhibition was observed when
      sodium phytate was added. No significant difference in the inhibiting effect of
      phytate could be detected with additions ranging from the equivalent of 50-300 mg
      phytic acid to a meal containing egg white as the protein source. Our studies
      found no evidence that the inhibiting effect of phytate depends on the protein
      composition of the meal.

PMID- 8561062
TI  - Rapid modulation of lung and liver macrophage phospholipid fatty acids in
      endotoxemic rats by continuous enteral feeding with n-3 and gamma-linolenic fatty
      acids.
AB  - Dienoic eicosanoids derived from phospholipid arachidonic acid (AA) in lung and
      liver macrophages promote leukosequestration, thrombosis, and tissue injury.
      Current enteral diets (diet A) are enriched with linoleic acid (LA), a precursor
      of AA. Novel diets low in LA and containing eicosapentaenoic acid (EPA) and gamma
      linolenic acid (GLA) foster formation of less inflammatory eicosanoids. The study
      objective was to assess the rapidity and extent of LA and AA displacement in vivo
      from alveolar macrophage (AM phi), lung, and liver Kupffer and endothelial (KE)
      cell phospholipids in rats fed enterally with diets enriched with 5.3% (by wt)
      EPA and either 1.2% or 4.6% GLA (diets B and C, respectively). After surgical
      placement of catheters, the rats were fed enterally and co-infused intravenously
      with either endotoxin or vehicle continuously for 3 or 6 d. Rats given either
      diet B or C had significantly lower (P < 0.01) relative percentages of AA and LA
      within the AM phi, lung, and KE cell phospholipids, and concomitantly higher
      percentages of EPA compared with rats infused with diet A after 3 d of enteral
      feeding irrespective of endotoxin co-infusion. Incorporation of dihomo-gamma
      linolenic acid (DHGLA), the metabolite of GLA, into lung and KE phospholipids was
      significant in rats given diet C. Most of the changes in fatty acid composition
      occurred by day 3. The polyunsaturated fatty acid composition of AM phi, lung,
      and KE cell phospholipids can be rapidly modified by continuous short-term
      enteral feeding with EPA- and GLA-enriched diets irrespective of concurrent
      endotoxemia.

PMID- 8561063
TI  - Hyperhomocysteinemia in chronic alcoholism: correlation with folate, vitamin B
      12, and vitamin B-6 status.
AB  - Serum homocysteine concentrations have been shown to be a sensitive functional
      indicator of intracellular folate, vitamin B-12, and vitamin B-6 status. Chronic
      alcoholism is known to interfere with one-carbon metabolism, for which the above
      vitamins serve as coenzymes. In the present study, these vitamins were assessed
      in 32 chronic alcoholics and 31 healthy volunteers by measuring blood vitamin
      concentrations as well as serum homocysteine concentrations. In chronic
      alcoholics, serum pyridoxal 5'-phosphate and red blood cell folate concentrations
      were significantly lower than in the control subjects (P < 0.001 and P = 0.008,
      respectively). Mean serum homocysteine was twice as high in chronic alcoholics
      than in nondrinkers (P < 0.001). Beer consumers had significantly lower
      concentrations of homocysteine compared with drinkers of wine or spirits (P =
      0.05). These results suggest that by interfering with folate or vitamin B-6
      metabolism, chronic alcohol intake may impair the disposal of homocysteine
      through the transmethylation or transsulfuration pathways.

PMID- 8561064
TI  - Effects of diet and exercise on common cardiovascular disease risk factors in
      moderately obese older women.
AB  - Diet and exercise studies of premenopausal women have shown reductions in obesity
      and other cardiovascular disease (CVD) risk factors. Forty-one healthy,
      moderately obese (120-140% of ideal body weight, LBW), postmenopausal women (65.6
      +/- 3.3 y) participating in 24-wk diet or diet + exercise programs were studied
      to determine whether similar CVD risk reduction would occur. Daily energy need
      (DEN) was estimated from basal energy expenditure and self-reported activity. The
      diet + exercise group (n = 16) reduced their daily energy intake (DEI) by 2092 kJ
      from their DEN and expended 837 kJ/d in walking and resistance exercise. The two
      diet-only groups (n = 13 and n = 12) reduced their DEI by 2092 and 2929 kJ from
      their DEN, respectively. Body weight, waist-to-hip and subscapula-to-triceps
      ratios, blood lipids (total, low-density-lipoprotein, and high-density
      lipoprotein cholesterol, and triacylglycerols), glucose, and insulin
      concentrations were measured at baseline and after 12 and 24 wk of diet and diet
      + exercise. Data were analyzed by using analysis of variance with repeated
      measures (P < or = 0.05) and Tukey's post hoc test. Loss of body weight was
      significant for all groups between baseline and 12 and 24 wk (baseline: 79.3 +/-
      7.6 kg; 12 wk; 75.1 +/- 7.7 kg; 24 wk; 72.8 +/- 8.0 kg) but did not differ among
      groups. No significant time or treatment effects were observed between baseline
      and 24 wk for changes in mean blood lipid, glucose, and fasting insulin
      concentrations or measures of body fat distribution. Although 24 wk of diet or
      diet+exercise significantly reduced body weight in this group, this loss in body
      weight was not accompanied by a reduction of other commonly accepted CVD risks.

PMID- 8561065
TI  - Effects of National Cholesterol Education Program Step 2 diets relatively high or
      relatively low in fish-derived fatty acids on plasma lipoproteins in middle-aged
      and elderly subjects.
AB  - The effects of two National Cholesterol Education Program (NCEP) Step 2 diets (<
      or = 30% of energy as total fat, < 7% of energy as saturated fat, and < 200 mg
      cholesterol/d), one relatively high and the other relatively low in fish-derived
      fatty acids, on plasma lipoprotein concentrations and blood pressure were
      compared in 22 men and women with a mean (+/- SD) age of 63 +/- 10 y. Subjects
      were placed on a baseline diet similar to the diet currently consumed in the
      United States (35% of energy as total fat, 14% of energy as saturated fat, 35 mg
      cholesterol/MJ) for 6 wk and then on either an NCEP Step 2 diet relatively high
      in fish (Step 2 high-fish, n = 11) or relatively low in fish (Step 2 low-fish, n
      = 11) for 24 wk. All food and drinks were provided. Compared with baseline
      values, consumption of both the Step 2 high-fish and the Step 2 low-fish diets
      under weight-stable conditions was associated with significant decreases in
      plasma concentrations of total cholesterol (-14% and -19%, respectively), low
      density-lipoprotein (LDL) cholesterol (-15% and -20%, respectively), and high
      density-lipoprotein (HDL) cholesterol (-11% and -17%, respectively).
      Postprandial, but not fasting, triacylglycerol concentrations were significantly
      reduced during consumption of the Step 2 high-fish diet. There were no
      significant changes in these indexes after consumption of the Step 2 low-fish
      diet compared with the baseline diet. LDL particle size decreased significantly (
      12%) only in subjects on the Step 2 low-fish diet. Both Step 2 diets caused small
      but significant reductions in diastolic blood pressure. Our results indicate that
      NCEP Step 2 diets relatively high or relatively low in fish are both effective in
      significantly reducing total and LDL-cholesterol concentrations without changes
      in the ratio of total cholesterol to HDL cholesterol under controlled weight
      stable conditions in middle-aged and elderly subjects. A beneficial effect on
      diastolic blood pressure was also observed.

PMID- 8561066
TI  - Elevated plasma concentration of reduced homocysteine in patients with human
      immunodeficiency virus infection.
AB  - Oxidative stress has been suggested to be an important factor in the
      immunopathogenesis of human immunodeficiency virus (HIV) infection. Reduced
      plasma thiols may lead to production of reactive oxygen species, thus
      contributing to the oxidative stress. We quantified the total, reduced, and
      protein-bound forms of the thiols homocysteine, cysteine, cysteinylglycine, and
      methionine in plasma from 21 HIV-infected patients and 15 healthy control
      subjects and compared the results with clinical and immunologic indexes. The HIV
      infected patients had significantly higher concentrations of reduced homocysteine
      in plasma compared with control subjects. No significant differences in reduced
      homocysteine concentrations were noted when asymptomatic and symptomatic HIV
      infected patients were compared, and we did not find any relation between reduced
      homocysteine concentrations and other markers of immunodeficiency. The HIV
      infected patients had normal total homocysteine concentrations. The reduced
      cysteinylglycine concentration tended to be elevated in the patient group. No
      differences between HIV-infected patients and control subjects were found for
      reduced or total cysteine. Compared with control subjects, the HIV-infected
      patients had lower concentrations of methionine in plasma, and a significant
      correlation was found between low concentrations of methionine and low CD4+
      lymphocyte counts in blood. Elevated concentrations of reduced homocysteine could
      possibly contribute to formation of reactive oxygen species, leading to
      accelerated immunologic deterioration and increased HIV replication.

PMID- 8561067
TI  - Differential effects of saturated and monounsaturated fat on blood glucose and
      insulin responses in subjects with non-insulin-dependent diabetes mellitus.
AB  - To compare the metabolic effect of coingestion of saturated and monounsaturated
      fats with potato, 12 subjects with non-insulin-dependent diabetes mellitus
      (NIDDM) received 300 g mashed potato alone or in combination with 40 g olive oil,
      80 g olive oil, 50 g butter, or 100 g butter, respectively. The blood glucose
      response area to potatoes with 100 g butter (448 +/- 68 mmol.240 min/L) was
      significantly lower than after the four other meals: 596 +/- 63 (potato alone),
      649 +/- 82 (potato + 40 g olive oil), 587 +/- 80 (potato + 50 g butter), and 604
      +/- 81 (potato + 80 g olive oil) nmol.240 min/L, P < 0.05, respectively. The
      insulin response was significantly increased by adding 50 and 100 g butter,
      whereas addition of 40 and 80 g olive oil had no effect. The fatty acid
      concentration was higher when 100 g butter was added to the potato meal than when
      it was not (0.67 +/- 0.05 compared with 0.48 +/- 0.07 mmol/L, P < 0.05). Fatty
      acid concentrations were similar to those found for the other meals. The
      triacylglycerol response increased in a dose-dependent manner with the fat
      content of the meals irrespective of the type of fat. We conclude that butter
      increases the insulin response more than does olive oil, and large amounts of
      butter also increase fatty acid and triacylglycerol concentrations.

PMID- 8561068
TI  - Body fat distribution and non-insulin-dependent diabetes: comparison of a fiber
      rich, high-carbohydrate, low-fat (23%) diet and a 35% fat diet high in
      monounsaturated fat.
AB  - The effects of a fiber-rich, high-carbohydrate, low-fat (HCLF) diet and a
      modified-fat (MF) diet high in monounsaturated fat on body fat distribution were
      examined by dual-energy X-ray absorptiometry (DXA) in 16 subjects with non
      insulin-dependent diabetes (NIDDM) during a randomized crossover study. Subjects
      lost similar amounts of body fat consuming the HCLF and MF diets (-0.83 +/- 0.37
      and -0.87 +/- 0.40 kg, respectively) despite a marked difference in total fat
      consumption. With the MF diet, the ratio of upper- to lower-body fat (UF:LF)
      remained unchanged because fat was lost proportionately from the upper and lower
      body. In contrast, with the HCLF diet, a disproportionate loss of lower-body fat
      caused the UF:LF to increase. The effects of diet on regional body fat loss were
      significant (P < 0.05, two-factor repeated-measures ANOVA).

PMID- 8561069
TI  - n-3 fatty acids do not enhance LDL susceptibility to oxidation in
      hypertriacylglycerolemic hemodialyzed subjects.
AB  - Recent data suggest that treatment with n-3 fatty acids could enhance the
      susceptibility of plasma low-density-lipoprotein (LDL) to oxidation. Twelve
      hypertriacylglycerolemic, hemodialyzed patients were treated with 2.5 g n-3 fatty
      acids/d for 2 mo. Treatment was then withdrawn for 2 mo (washout phase). Plasma
      total cholesterol and LDL cholesterol increased significantly (9% and 28%) and
      plasma triacylglycerols decreased significantly after the n-3 phase compared with
      baseline and washout values. LDL susceptibility to oxidation was tested by
      oxidation of LDL particles with 2,2'-azobis (2-amidinopropane) dihydrochloride
      (AAPH). No significant changes were observed for the lag phase and the
      peroxidation rate. The vitamin E content of LDL also did not change
      significantly. The results thus suggest that a daily dosage of 2.5 g n-3 fatty
      acids does not enhance LDL susceptibility to oxidation, while retaining its
      hypotriacylglycerolemic effect.

PMID- 8561070
TI  - Fish oil supplementation inhibits the expression of major histocompatibility
      complex class II molecules and adhesion molecules on human monocytes.
AB  - To test the hypothesis that fish oil supplementation can inhibit the expression
      of functionally associated molecules on the surface of human blood monocytes, we
      randomly assigned 12 healthy adults to receive either an n-3 polyunsaturated
      fatty acid-rich fish oil supplement for 21 d or to receive no supplement. The
      percentage of monocytes expressing major histocompatibility complex (MHC) class
      II molecules (HLA-DR, -DP, and -DQ), intercellular adhesion molecule-1, and
      leukocyte-function-associated antigen-1, and the intensity of expression of each
      molecule were quantified before and after the study period. Monocytes were
      examined immediately after blood sampling and again after incubation in serum
      free culture medium for 24 h in the presence of interferon-gamma to up-regulate
      expression of MHC class II molecules by the monocytes. The intensity of
      expression of all the monocyte surface molecules examined was significantly
      reduced after fish oil supplementation (P < 0.025), although there was no change
      in the percentage of monocytes expressing each molecule. After incubation with
      interferon-gamma, there was a similar inhibition of surface molecule expression
      (with the exception of HLA-DQ) by monocytes from the fish oil-supplemented group,
      and there was a reduction in the percentage of monocytes expressing both HLA-DR
      and -DP molecules (P < 0.025). No significant changes were observed in the
      reference group. Dietary supplementation with fish oil can inhibit the expression
      of surface molecules involved in the function of human antigen-presenting cells,
      a potential mechanism by which n-3 fatty acids may suppress cell-mediated immune
      responses.

PMID- 8561071
TI  - Immunologic effects of marine- and plant-derived n-3 polyunsaturated fatty acids
      in nonhuman primates.
AB  - The effect of marine- and plant-derived n-3 polyunsaturated fatty acids (PUFAs)
      on T cell-mediated immune response was studied in cynomolgus monkeys. Animals
      were first fed a 14-wk baseline diet; 10 animals were then fed diets containing
      1.3% or 3.3% of energy as eicosapentaenoic acid (EPA) plus docosahexaenoic acid
      (DHA) which the other 10 were fed diets containing 3.5% or 5.3% of energy as
      alpha-linolenic acid (ALA) for two consecutive 14-wk periods. Both diets
      significantly decreased the percentage of T cells (except 1.3% EPA + DHA), T
      helper cells (except 1.3% EPA + DHA and 3.5% ALA), and T suppressor cells.
      Proliferative response of lymphocytes to T cell mitogens significantly increased
      after the diet containing 3.3% EPA + DHA. Interleukin 2 production significantly
      increased after the diets containing 1.3% and 3.3% EPA + DHA. No significant
      changes in mitogenic response or interleukin 2 production were found after ALA
      diets. Feeding 1.3% or 3.3% EPA + DHA or 5.3% ALA significantly suppressed
      prostaglandin E2 production in response to T cell mitogens. Plasma tocopherol
      concentrations were decreased significantly only in monkeys fed ALA diets. We
      conclude that after adjustment for the tocopherol concentration, marine-derived n
      3 PUFAs but not plant-derived n-3 PUFAs increased T cell-mediated mitogenic
      response and interleukin 2 production. This is most likely due to diet-induced
      quantitative differences in cellular fatty acid composition and, thus, in
      prostaglandin E2 production and tocopherol status.

PMID- 8561072
TI  - Total energy expenditure and basal metabolic rate.

PMID- 8561073
TI  - Thrombolytic therapy and implications for the clinical laboratory.

PMID- 8561074
TI  - Genotypic analysis of primary head and neck squamous carcinoma by combined
      fluorescence in situ hybridization and DNA flow cytometry.
AB  - Concurrent DNA flow cytometric (FCM) and fluorescence in situ hybridization
      (FISH) analyses were prospectively performed on 24 primary untreated head and
      neck squamous carcinomas for characterization of the genotypic and phenotypic DNA
      aberrations of these neoplasms. Eleven tumors (42.0%) manifested DNA diploidy (DI
      = 1.00) and 15 (58.0%) had DNA aneuploidy (DI < or > 1.00) by FCM. Fluorescence
      in situ hybridization results showed aneusomy in the majority of DNA diploid and
      in all DNA aneuploid tumors. The extent of the abnormalities for individual
      chromosomes and the number of involved chromosomes in a given DNA diploid or
      aneuploid tumor were significantly different. Overall, a statistical correlation
      between the FCM DNA index (DI) and the magnitude of the chromosomal aberration by
      FISH was found. Our results also show a significant association between the DI
      and histologic differentiation and stage of disease in these neoplasms. In
      conclusion, (1) chromosomal aneusomy characterizes most DNA diploid (DI = 1.00)
      and all DNA aneuploid (DI < or > 1.00) head and neck squamous carcinomas; (2)
      polysomy is the most prevalent finding; (3) loss of the Y chromosome in tumors
      from male patients is a consistent feature; (4) the FCM DI reflects net
      chromosomal gains or losses in these neoplasms; and (5) DNA aneuploidy is
      associated with tumor aggressiveness.

PMID- 8561075
TI  - Comparative study between cytology and dot-ELISA for early detection of bladder
      cancer.
AB  - Schistosomiasis remains one of the major public health problems of the tropics.
      Conservative estimates place the number of infected individuals at about 200
      millions. In Egypt, carcinoma of the urinary bladder associated with
      schistosomiasis is the foremost oncologic problem, because of its high frequency
      and the late presentation of cases. A newly developed monoclonal antibody CK1K10
      to keratinized grade 1 squamous cell carcinoma was used in a dot enzyme-linked
      immunosorbent assay (Dot ELISA) to test urine samples of 118 patients with
      bladder carcinoma, 291 patients with genitourinary pathology other than bladder
      carcinoma, in addition to 550 healthy controls. The overall sensitivity of the
      dot ELISA was 90% among 118 patients with bladder carcinoma. Twenty-seven of 33
      transitional cell carcinoma cases (82%), 68 of the 71 squamous cell carcinoma
      cases (96%), 7 of 10 undifferentiated tumors cases (70%), and 4 of 4
      adenocarcinoma were positive with this assay. The specificity was 90% in our
      sample population. A comparative study of diagnosis by cytology and dot ELISA was
      carried out in 57 patients with bladder carcinoma. Dot ELISA was found to be
      superior as a screening tool for high risk groups (P < .001 using chi-square
      test). Cytology detected 21% of transitional cell carcinoma, 68% of squamous cell
      carcinoma, 50% of adenocarcinoma, and 86% of undifferentiated tumors. The dot
      ELISA assay should be useful for screening high-risk groups because it does not
      require sophisticated equipment, is noninvasive, does not require highly trained
      staff, and can be performed in less than 30 minutes.

PMID- 8561076
TI  - An algorithmic approach to thyroid function testing in a managed care setting. 3
      year experience.
AB  - An algorithm (directed thyrotropin [TSH], directed thyroid testing algorithm
      [DRTSH]) for the initial evaluation and monitoring of thyroid function was
      established in our institution in 1990. The algorithm begins with measurement of
      TSH by a sensitive immunoassay. If TSH is either < 0.4 mU/L or > 5.5 mU/L, a free
      thyroid index (T4 x Resin Uptake Ratio (RU)) is automatically performed on the
      same sample on the same day. In the setting of a large, predominately outpatient,
      prepaid health care population, the algorithm reduces unnecessary testing and
      focuses resources on the patients who need it. Three years after its
      introduction, physician acceptance of this approach is high ( > 90%), test
      utilization is reduced, test turnaround time is reduced, and significant cost
      savings can be demonstrated.

PMID- 8561077
TI  - Multivariate statistical analysis for pathologist. Part I, The logistic model.
AB  - This paper reviews concepts of multivariate statistical modeling via the logistic
      regression model, which has become very popular for modeling the relationship
      between a positive clinical outcome and a variety of predictor variables. The
      process is illustrated using a composite of data from three large prostate
      specific antigen based screening studies of prostate cancer.

PMID- 8561078
TI  - President, American Society of Clinical Pathologists.

PMID- 8561079
TI  - A point of gross anatomy.

PMID- 8561080
TI  - Differential diagnosis of malignant effusions.

PMID- 8561081
TI  - Ethylenediamine tetraacetic acid-associated leukoagglutination.

PMID- 8561082
TI  - Prediction of fetal lung maturity in infants of diabetic mothers using the FLM
      S/A and disaturated phosphatidylcholine tests.
AB  - The authors evaluated the performance of the amniotic fluid surfactant to albumin
      ratio (FLM S/A), and disaturated phosphatidylcholine (DSPC) tests in assessing
      fetal lung maturity in infants of mothers with insulin-dependent diabetes
      mellitus antedating pregnancy. The distribution of the study population (n = 180)
      by class of diabetes was class B (27%); class C (28%); class D (29%); class F, FR
      and T (8%); and class R patients (8%). The diagnosis of respiratory distress
      syndrome (RDS) was the standard for evaluating the performance of FLM S/A and
      DSPC. The mean estimated gestational age was 37.4 weeks. Three infants (1.7%)
      were diagnosed with RDS. All three were delivered before 36 weeks. FLM S/A at the
      cut-off for "maturity" of > or = 70 mg/g, had a sensitivity of 66.6%, specificity
      of 94.9%, positive predictive value (PPV) of 18.2%, and negative predictive value
      (NPV) of 99.4%. DSPC at the cut-off for "maturity" of 1,000 micrograms/dL, had
      identical sensitivity and NPV, but lower specificity (89.2%) and PPV (9.5%) than
      FLM S/A. Both tests mispredicted maturity in the same case of RDS. The false
      "mature" rate of FLM S/A was 0.6% (95% confidence interval 0.0%-3.2%). The FLM
      S/A result of > or = 70 mg/g, obtained at or near-term, is a reliable predictor
      of the absence of RDS in infants of mothers with diabetes mellitus antedating
      pregnancy.

PMID- 8561083
TI  - Image analysis detects lineage-specific morphologic markers in leukemic blast
      cells.
AB  - This report outlines the morphologic classification of acute myeloid (AML: French
      American-British FAB classification: M1) and lymphoid (ALL) leukemia by automatic
      image analysis and the correlation to immunologic and cytochemical
      classification. The investigation was carried out on Romanowsky-Giemsa stained
      bone marrow (n = 15) and blood smears (n = 10) from 25 patients with primary
      acute leukemia. The cases had been classified as of myeloid or lymphoid origin by
      three hematologic centers using immunochemistry or cytochemistry, but the
      specimens were submitted to the authors' laboratory without the diagnosis. The
      nuclear and cytoplasmic pattern of the blast cells were analyzed by a high
      resolution image analysis system and the measured and calculated cell features
      were sorted by means of a classifier program (CART). The image analysis
      classification was then compared with the immunophenotypical and cytochemical
      classification. Blood blast cells showed nuclear features that were significantly
      correlated to a myeloid or lymphoid immunophenotype. In contrast, bone marrow
      blast cells displayed overlapping and therefore nondiscriminating nuclear
      features. However, by generating a learning data set using the immunophenotypes
      the classifier program found specific cytoplasmic features that eventually
      permitted a differentiation into myeloid or lymphoid subtypes. In summary, the
      authors suggest that high resolution image analysis of leukemic blast cells
      detect nuclear and cytoplasmic features that are associated with the
      immunophenotype and therefore with the lineage determination of the cell. With
      this new objective and reproducible approach of morphologic cell analysis, it
      might not only be possible to classify blast cells with minimal cellular
      differentiation, but furthermore to discover prognostic features because the
      remarkable difference in classification quality between blood and bone marrow
      blast cells reported in this study, might be of biologic relevance and requires
      further investigation.

PMID- 8561084
TI  - Thoughts on the development of hepatocellular carcinoma in cirrhotic and
      noncirrhotic livers.

PMID- 8561085
TI  - CD5+ extranodal marginal zone B-cell (MALT) lymphoma. A low grade neoplasm with a
      propensity for bone marrow involvement and relapse.
AB  - Three cases of extranodal marginal zone B-cell lymphoma (low grade B-cell
      lymphoma of mucosa-associated lymphoid tissue [MALT] type) in which the
      neoplastic B cells expressed the CD5 antigen are reported. The patients included
      2 men and 1 woman, aged 44, 62, and 77 years. In all three cases, the histologic
      features were typical of marginal zone/MALT lymphoma, with reactive follicles,
      marginal zone (centrocyte-like) cells, and plasma cells. Pseudofollicles,
      prolymphocytes, and paraimmunoblasts were absent. In all cases, lymphoma from one
      or more sites expressed monotypic immunoglobulin (2 IgM kappa, 1 IgM lambda), pan
      B cell antigens and CD5. Two of 3 cases expressed CD43; one case expressed CD23.
      No case showed overexpression of the bcl-1 protein, cyclin D1. Interphase
      cytogenetic analysis revealed trisomy 3 in one of two cases examined. The two
      male patients presented with lymphoma in the ocular adnexa. One of them had
      marrow involvement, cervical lymphadenopathy and peripheral blood involvement at
      presentation; 24 months later, he developed a relapse in subcutaneous tissue. The
      second patient had marrow involvement 3 years later, at the time of recurrence of
      his orbital disease. The third patient presented with lymphoma at the base of the
      tongue. She subsequently developed lymphoma involving the left upper eyelid and
      right lacrimal sac and duct, the marrow, and the nasopharynx between 63 and 95
      months after initial presentation. All of these patients presented with disease
      involving sites in the head and neck and all had multiple relapses or recurrences
      with bone marrow involvement at the time of presentation (1 case) or at relapse
      (2 cases). The presence of CD5 may be a marker for cases of MALT lymphoma with a
      tendency for persistent or recurrent disease, for dissemination to the marrow and
      other extranodal sites, and for leukemic involvement of the peripheral blood.

PMID- 8561086
TI  - Determination of lymphocyte immunophenotypic values for normal full-term cord
      blood.
AB  - Normal reference values for flow cytometric immunophenotypic lymphocyte markers
      for cord blood (CB) were determined using sufficient numbers of subjects for
      clinical laboratory use. Samples from 202 normal gestations were processed by
      whole blood lysis and analyzed in the following combinations: CD14/45, CD4/3,
      CD8/3, CD45RA/4, CD29/4, CD56/3, Cd19/3, CD19/10. Thirty-five adult laboratory
      volunteers were analyzed as controls. When compared to adults, CB showed
      increased relative percentages of naive T-helper cells, B cells, immature B
      cells, and CD8+3-cells and decreased T cells, cytotoxic T cells, activated T
      helper cells, and large granular lymphocytes (CD56+3+). Significant differences
      were also found when CB samples were stratified by sex and race. These results
      provide clinical laboratory normal reference values for lymphocyte markers for
      CB, demonstrate the need for determining separate standard reference values for
      significantly different patient populations, provide the basis for future
      investigation of pathologic gestations and for clinical laboratory applications,
      and provide insight into early immunologic development.

PMID- 8561087
TI  - Exponentially adjusted moving mean procedure for quality control. An optimized
      patient sample control procedure.
AB  - The idea of using patient samples as the basis for control procedures elicits a
      continuing fascination among laboratorians, particularly in the current
      environment of cost restriction. Average of normals (AON) procedures, although
      little used, have been carefully investigated at the theoretical level. The
      performance characteristics of Bull's algorithm have not been thoroughly
      delineated, however, despite its widespread use. The authors have generalized
      Bull's algorithm to use variably sized batches of patient samples and a range of
      exponential factors. For any given batch size, there is an optimal exponential
      factor to maximize the overall power of error detection. The optimized
      exponentially adjusted moving mean (EAMM) procedure, a variant of AON and Bull's
      algorithm, outperforms both parent procedures. As with any AON procedure, EAMM is
      most useful when the ratio of population variability to analytical variability
      (standard deviation ratio, SDR) is low.

PMID- 8561088
TI  - A rapid and inexpensive method for processing induced sputum for detection of
      Pneumocystis carinii.
AB  - The authors describe a method to process induced sputum specimens for detection
      of Pneumocystis carinii which is simple, rapid and inexpensive. Induced sputum
      and bronchoalveolar lavage (BAL) were obtained within a 24-hour period from 41
      patients who were HIV-positive and had pulmonary symptoms suspicious for P
      carinii pneumonia. Induced sputum or BAL fluid was placed into Saccomanno's
      fixative, blended, and centrifuged. The sediment was stained for P carinii cysts
      by a modified method with Fungi-Fluor Solution A (Polysciences, Warington, PA)
      and the Genetic Systems Pneumocystis carinii Immunofluorescence Antibody (Genetic
      Systems, Seattle, WA). The Genetic Systems stain on the BAL specimen was positive
      in 35 patients and was the standard for comparison. With a single induced sputum,
      the Genetic Systems stain detected 31 (89%) positive patients, whereas the Fungi
      Fluor stain detected 21 (60%). The sensitivity for detecting P carinii cysts in
      induced sputum was significantly greater (P < 0.05) for the Genetic Systems
      stain.

PMID- 8561089
TI  - Quality perceptions of microbiology services. A survey of infectious diseases
      specialists.
AB  - Opinions about the quality of their primary microbiology laboratory were received
      from more than 500 practicing infectious diseases specialists by a nationally
      distributed questionnaire. Approximately 92% of the respondents' primary
      laboratories were hospital-based. These sophisticated users rated the quality of
      their microbiology laboratories to be generally high, with bacteriology receiving
      highest scores and parasitology the lowest scores. Fortunately, the serious
      problems, such as failing to call a critical result and culture mishandled in the
      laboratory, were experienced rarely. Laboratories directed by pathologists with
      specialty microbiology training, PHD microbiologists, and infectious diseases
      specialists were judged to be of highest quality. American Board of Medical
      Microbiology certification of the laboratory director was related to higher
      overall quality perceptions. Whereas physician-customer opinions may not directly
      measure a laboratory's analytic quality, they are an important performance
      measure on which laboratories can base quality improvement activities in both
      service and analytical aspects of performance.

PMID- 8561090
TI  - Early monitoring of serum cardiac troponin I for assessment of coronary
      reperfusion following thrombolytic therapy.
AB  - The authors report the use of cardiac troponin I (cTnI) for the early,
      noninvasive determination of coronary reperfusion following thrombolytic therapy.
      Cardiac troponin I, creatine kinase (CK)-MB, and myoglobin concentrations were
      measured in early serum specimens at 30, 60, and 90 minutes after initiation of
      therapy (0 minutes) in 25 consecutive patients given front-loaded rt-PA during
      acute myocardial infarction. Angiography, determined at 90 minutes after therapy,
      was used to classify patients as follows: group I (n = 17) reperfusion (TIMI flow
      grade 2, 3); and group 2 (n = 8) absence of reperfusion (TIMI flow grade 0, 1).
      The authors calculated the ratio increase in cTnI (delta cTnI), CK-MB (delta CK
      MB), and myoglobin (delta myoglobin) 90 minutes after therapy in group 1 and 2.
      Serum cTnI, CK-MB and myoglobin concentrations significantly increased at 60 and
      90 minutes in group 1, but not in group 2. Delta cTnI, delta CK-MB, and delta
      myoglobin levels were significantly increased in group 1 versus group 2 at 90
      minutes. Further, delta cTnI was significantly greater at 90 minutes within group
      1 compared to delta CK-MB and delta myoglobin. The sensitivity for detecting
      reperfusion at 90 minutes angiography using threshold values of 6.0 for delta
      cTnI, 7.0 for delta CK-MB, and 5.0 for delta myoglobin were: delta cTnI 82.4%;
      delta CK-MB 64.7%; delta myoglobin 76.5%; respectively. This study indicates that
      early serial measurements of cTnI were a more accurate predictor of early
      coronary artery reperfusion 90 minutes after thrombolytic therapy compared to CK
      MB and myoglobin. Larger population studies will be necessary to confirm these
      finding.

PMID- 8561091
TI  - Hepatocellular carcinoma in cirrhotic and noncirrhotic livers. A clinico
      histopathologic study of 804 North American patients.
AB  - This study examined clinico-histopathologic differences between North American
      patients who developed hepatocellular carcinoma with and without cirrhosis.
      Histologic slides and clinical records of cases were reviewed. Cases were
      classified according to defined histopathologic criteria. Analyses were performed
      using appropriate tests. A total of 42.6% of cases were noncirrhotic. The
      trabecular type of hepatocellular carcinoma was the most common growth pattern in
      both groups. Patients with cirrhosis were significantly older, had high grade
      tumors, and local portal venous invasion significantly more often than patients
      without cirrhosis. Encapsulated tumors occurred in significantly more in patients
      without cirrhosis. Patients without cirrhosis survived longer than patients with
      cirrhosis (P < .0001) and had a better 5-year survival experience. On average, in
      patients with cirrhosis, serum aspartate transaminase and total serum bilirubin
      were significantly greater, and serum albumin was significantly lower. In
      general, hepatocellular carcinoma in North American patients with cirrhosis
      tended to be less well differentiated than those found among patients without
      cirrhosis. The pathology, natural history, and prognosis of this tumor is
      significantly influenced by the presence or absence of cirrhosis in the
      nonneoplastic liver, and the presence of cirrhosis portends a poorer prognosis.

PMID- 8561092
TI  - Adrenal cortical neoplasms. A study of 56 cases.
AB  - Fifty-six cases of adrenal cortical neoplasm with a minimum of 5 years follow-up
      are presented: 48 carcinomas and 8 adenomas. Adenomas typically had a maximal
      mitotic rate of fewer than 2 mitotic figures per 10 high-power fields (all
      cases), a prominent small nest growth pattern (7 cases), predominantly clear or
      foamy cytoplasm (6 cases), and no tumor necrosis (all cases), whereas carcinomas
      were characterized by at least 4 mitotic figures (often many more) per 10 high
      power fields in the most active area (all cases), lack of a significant small
      nest growth pattern component (45 cases--solid or trabecular growth most common),
      at least a considerable proportion of cells with eosinophilic cytoplasm (all
      cases), and tumor necrosis (45 cases). Carcinomas were almost always larger than
      adenomas, but two adenomas (5.9 cm and 7 cm) overlapped in size with the four
      smallest carcinomas (5.5 cm, 6 cm, 7 cm, and 7 cm, respectively). The patients
      with adenomas were older on the average than those with carcinomas (median 58
      years, range 31-71 years versus median 41 years, range 5 months-66 years). Two
      adenomas and 19 carcinomas were functional. No patient with adenoma had
      recurrence of tumor after excision, whereas all but nine carcinoma patients died
      of tumor, after 1 to 183 months. Among carcinoma patients, survival was
      significantly shorter when distant metastases were manifest at diagnosis (P =
      .0003). There was a trend toward shorter survival with higher mitotic rates and
      functional tumors, but neither these nor any other parameter had a statistically
      significant relationship to survival or tumor behavior when presence/absence of
      metastases at diagnosis was taken into account.

PMID- 8561093
TI  - Hepatic expression of hepatitis B virus genome in chronic hepatitis B virus
      infection.
AB  - The expression of hepatitis B virus (HBV) DNA in the liver was studied by
      nonisotopic in situ hybridization and correlated with liver histology, different
      phases in the natural evolution of chronic hepatitis B, and hepatic expression of
      HBV antigens in 251 Chinese patients with chronic HBV infection. A good
      correlation was found between the detection of HBV-DNA by in situ hybridization
      and serum HBV-DNA (P < .01). Chronic active hepatitis had the highest HBV-DNA
      detected in cytoplasm and nuclei, compared with livers showing minimal change,
      chronic persistent hepatitis, cirrhosis, and hepatocellular carcinoma. HBV-DNA in
      cytoplasm exceeded HBV-DNA in nucleus in all patients except in livers with
      hepatocellular carcinoma. Hepatic HBV-DNA correlated with disease activity (P <
      .02) and the correlation was highly significant with intralobular activity (P <
      .001). Patients in the early viral replicative phase of infection had higher
      levels of cytoplasmic and nuclear HBV-DNA compared with the late viral
      nonreplicative phase. Cytoplasmic and nuclear HBV-DNA correlated with hepatic
      expression of HBcAg and HBsAg (P < .05 in both cases), but not with HBeAg. These
      data indicate that hepatic expression of HBV-DNA follows the natural history of
      chronic HBV infection and is associated with active liver disease.

PMID- 8561094
TI  - Antral atrophy, Helicobacter pylori colonization, and gastric pH.
AB  - The association between the topographic distribution of Helicobacter pylori
      colonization, inflammation and atrophy of the gastric mucosa, and fasting gastric
      pH was studied in a population with high prevalence of multifocal atrophic
      gastritis. Increasing atrophy of the antrum was associated with decreasing H
      pylori colonization of the antrum itself, but increasing colonization of the
      corpus. Advanced atrophy was associated with high fasting gastric pH. However,
      after therapeutic eradication of H pylori, inflammation subsided and gastric pH
      decreased indicating improved acid secretion despite persistent atrophy. The
      authors propose that antral atrophy fosters the colonization of oxyntic mucosa by
      H pylori, thus impairing acid secretion and causing hypochlorhydria that may
      further promote colonization of the oxyntic mucosa. Eradication of H pylori
      significantly improves hypochlorhydria. It may restore acid secretion in most
      patients, regardless of the presence of atrophy, which is an effect that may be
      of great benefit in halting the process of gastric carcinogenesis.

PMID- 8561095
TI  - Gender differences in high-risk sex behaviours among heterosexual drug injectors
      and crack smokers.
AB  - This study was designed to assess gender differences in high-risk sex behaviors
      related to the transmission of HIV among injection drug users (IDUs) and crack
      smokers. Using a standard national survey instrument, 593 verified drug users
      were questioned about their sexual activities and drug use in the 30 day period
      prior to the interview. High-risk sex behaviors included nonuse of condoms,
      exchanging sex for drugs or money, sex with an IDU, and sex with more than one
      partner. Results showed that IDUs who engaged in needle risk practices were more
      likely report nonuse of condoms than IDUs who practiced safer needle use. African
      American ethnicity was a more powerful determinant of exchanging sex than smoking
      crack cocaine. Sex with more than one partner in the previous 30 day was reported
      by 11% of married males and 15% of married females. Independently, marital status
      was found to be a marker for high-risk sex behaviors, in particular, sex with an
      IDU and nonuse of condoms, behaviors reported more often by married than
      unmarried respondents. Needle risk, more common among females than males, was
      associated with sex with an IDU. Approximately one-fourth of the injectors
      reporting sex with only non-IDUs also reported needle risk, sex with more than
      one partner, and nonuse of condoms. These findings show the dual threat drug
      injectors face for HIV infection, through sex and needle risk behaviors, and the
      pivotal role IDUs play in the heterosexual transmission of HIV to noninjectors.

PMID- 8561096
TI  - Continuity of care in addictions treatment: the role of advocacy and coordination
      in case management.
AB  - Although advocacy and coordination are recognized as important aspects of the
      addictions treatment process, little research has been done in these areas. The
      present study examined advocacy and coordination at two programs where the
      mandate was assessment, referral, and case management. Both programs spent a
      similar proportion of client-related effort on advocacy and/or coordination
      (about 25% of contact time, accounting for about half of contacts made regarding
      clients). The majority of advocacy and coordination contacts were with other
      agencies about clients (the remainder with family and friends of clients). A
      framework for advocacy and coordination was developed that allowed contacts to be
      categorized into mutually exclusive advocacy or coordination activities. Advocacy
      was defined as any activity undertaken to obtain something for clients;
      coordination involved the giving or receiving of information regarding specific
      clients. Sources of variability in the provision of advocacy and coordination
      were found between the programs that could be attributed to differences between
      the systems within which the programs operated, as well as differences in program
      clientele. In terms of client characteristics, it was found that females were
      more likely than males to receive advocacy; those over 65 years were most likely
      to receive both advocacy and coordination; those who were referred by school or
      employer or by corrections were most likely to receive coordination; those with
      no prior treatment were most likely to receive advocacy; and self-referrals and
      those who had had prior treatment were most likely to receive neither advocacy
      nor coordination. Receiving advocacy or coordination was not found to reduce the
      need by clients for other case management services, such as supportive
      counseling. The findings are discussed in terms of the need for knowledge
      regarding highly variable aspects of treatment such as advocacy and coordination.
      New research approaches (as taken in the present study) are needed to begin to
      examine the contribution of these types of flexible and ancillary interventions
      to the recovery process.

PMID- 8561097
TI  - Reliability of sequential naloxone challenge tests.
AB  - To determine the reliability of serial naloxone challenges, five heroin addicts
      stabilized on methadone were given 0.2 mg naloxone intravenously on three
      consecutive days. Two-factor ANOVA revealed that the between-subjects effect
      accounted for at least 63% of the variance in each of the dependent measures, and
      the effect of challenge number for at most 22%. Withdrawal tended to be slightly
      more severe for the first challenge. Intraclass correlation coefficients were
      calculated for the area-under-the-curve of the change from baseline: subject
      rated (.74) and observer-rated (.71) withdrawal, pulse (.88), systolic blood
      pressure (.58), diastolic blood pressure (.85), and skin temperature (.63).

PMID- 8561098
TI  - Mazindol for relapse prevention to cocaine abuse in methadone-maintained
      patients.
AB  - We conducted a double-blind, randomized clinical trial of mazindol (n = 37) for
      the prevention of relapse to cocaine abuse in methadone-maintained patients who
      were in the "action" stage of change, i.e., had a history of cocaine dependence
      but who had been abstinent for at least 2 weeks prior to entry into the study.
      Eight-one percent of subjects completed the 12-week course of treatment. Overall,
      cocaine use during the study was comparatively low-17% of the urine screens
      submitted were positive for cocaine metabolite. Differences between the mazindol
      and placebo groups of rates of relapse, number of days to relapse, and cocaine
      use did not reach statistical significance, but were in the direction of a
      treatment effect. Results suggest that stage of abstinence initiation may be a
      potentially useful category to employ as an independent variable in future
      pharmacotherapy trials for the treatment of cocaine addiction in this patient
      population.

PMID- 8561099
TI  - A review of factors affecting treatment outcomes: Expected Treatment Outcome
      Scale.
AB  - The Expected Treatment Outcome Scales was developed to gather information on
      clients who abuse drugs or alcohol, to assess their severity of illness, and to
      evaluate the effectiveness of drug treatment in nonrandomized clinical studies.
      The scale is based upon a multiattribute value model reflecting the opinions of
      an expert panel. The experts identified 25 variables, or predictors of relapse,
      from which 48 questions were constructed. Answers to the questions are
      individually scored. These scores are summed to produce an overall Expected
      Treatment Outcome score. This paper focuses on the development and preliminary
      validation of the Expected Treatment Outcome Scale. Results of our analysis show
      a correlation of .89 between the experts' average ratings of hypothetical clients
      and scores based on our scale. This finding suggests that the Expected Treatment
      Outcome Scale has face validity and accurately simulates the experts' judgments
      regarding treatment outcome. Further research is necessary to assess the
      reliability as well as the concurrent and predictive validity of our instrument.

PMID- 8561100
TI  - Gender differences in early life risk factors for substance use/abuse: a study of
      an African-American sample.
AB  - Gender differences in risk and protective factors for substance use/abuse in
      early adulthood were studied. Comprehensive systematic data on African-American
      males (N = 318) and females (N = 322), from birth to 7 years of age, were
      available from the National Collaborative Perinatal Study. These subjects were
      retrieved for assessment at average age 24. There are more differences between
      males and females than there are similarities in regard to the early childhood
      variables that predict substance use in early adulthood. However, high activity
      and intensity of response during infancy (measured at 8 months of age) was found
      to predict later substance use for both males and females. This type of behavior
      is considered by use to be a trait of temperament and to suggest the possibility
      of a genetic predisposition. More risk factors were found for female than for
      males. The risk factors for females were primarily of two types: 1) Related to
      experiences with mother and with the family environment; and 2) Poor levels of
      intellectual functioning and academic performance, and abnormal mental status.

PMID- 8561101
TI  - Rapid admission and retention on methadone.
AB  - An open clinical trial was conducted to compare the effects of rapid (1-day)
      admission with slow (14-day) admission to methadone maintenance on pretreatment
      attrition, retention during treatment, and other outcomes. One hundred eighty-six
      illicit opioid users eligible for methadone maintenance were randomly assigned to
      rapid admission or slow admission, with 93 subjects assigned to each group. The
      random assignment produced two groups that were similar on 22 personal variables.
      All subjects admitted to treatment were followed for 1 year. Follow-up interviews
      were obtained with 155 (98%) of the 158 subjects admitted to treatment. During
      the period from initial contact to medication, only 4% of the rapid admission
      subjects but 26% of the slow admission subjects dropped out. The risk of dropout
      during slow admission was 6 times that during rapid admission. A higher
      percentage of rapid admission subjects, 43%, than of slow admission subjects,
      39%, remained continuously in treatment for 1 year, but the difference was not
      significant. The two subgroups that remained in treatment for 1 year did about
      equally well on measures of illicit drug use and social performance. The findings
      indicate that pretreatment attrition can be markedly reduced by prompt
      medication, and the prompt medication does not adversely affect retention during
      treatment or other outcomes.

PMID- 8561102
TI  - Ambulatory medical detoxification for alcohol.
AB  - In the past decade, ambulatory medical detoxification for alcohol withdrawal has
      become increasingly utilized due to pressures to contain cost of treatment and
      research demonstrating its effectiveness. The research that describes this area
      spans the last 15 years. This article reviews the available literature on
      ambulatory detoxification and attempts to summarize and synthesize what is known
      about this area in order to make ambulatory medical detoxification readily
      reproducible in clinical practice. Finally, this article concludes with an
      analysis of the advantages and disadvantages of outpatient alcohol detoxification
      as compared to inpatient treatment.

PMID- 8561103
TI  - Validity of the diagnostic interview schedule for detecting alcoholism in
      psychiatric inpatients.
AB  - This study examined the accuracy of the Diagnostic Interview Schedule (DIS) for
      indicating alcohol use disorder in a sample of patients hospitalized for
      depression. The Michigan Alcoholism Screening Test (MAST), with its established
      validity, was considered a good criterion against which to evaluate the DIS, and
      preferable to the clinician-assigned diagnosis in this regard. The rates of
      alcoholism in the sample were 31, 33, and 22.5% as yielded by the DIS, MAST, and
      physician's diagnosis of alcohol disorder, respectively. (The lower rate for
      physician's diagnosis may be due to the physician's not applying this diagnosis
      to recovered or currently abstinent alcohol patients.) Using the MAST's standard
      cutoff of five points as indicative of alcoholism, agreement with the DIS
      occurred in 91% of the cases, corresponding to a product moment coefficient of
      .79. It was concluded that the DIS alcoholism scale could be used, with
      reasonable confidence in its validity, for assessing alcoholism in psychiatric
      settings.

PMID- 8561104
TI  - The diagnostic value of BAC for identifying alcohol-related problems among DWI
      offenders: another look.
AB  - The present study examines the association between breath alcohol concentration
      (BAC) at arrest and problem drinking for a sample of 1,283 male DWI offenders in
      the US Army. The results indicated a moderate but statistically significant
      association between BAC at arrest and DSM-III diagnosis. BAC's ability to
      indicate problem drinking was also compared with the diagnostic ability of three
      well-known, paper-and-pencil instruments designed for that purpose. BAC performed
      as well in identifying problems with alcohol as did the MAST, the MacAndrew Scale
      of the MMPI, and the Vaillant.

PMID- 8561105
TI  - Gastrodontology: a clinical perspective worth consideration.

PMID- 8561106
TI  - Helicobacter pylori infection and blood groups.
AB  - OBJECTIVES: Bacterial attachment is a prerequisite for colonization of the
      gastric epithelial surface. Recently, it was demonstrated that the receptor for
      Helicobacter pylori is the blood group antigen Lewis b, which is exposed only in
      blood group O. We prospectively examined the prevalence of blood groups in H.
      pylori-positive and -negative patients. To avoid a genetic bias, we compared
      blood group prevalence of our patients with the general population of Israel.
      METHODS: In the 187 consecutive patients we studied, in addition to regular upper
      endoscopy, H. pylori status and blood group. Exposure to H. pylori was diagnosed
      when the results of two or more of three methods were found to be positive.
      RESULTS: Exposure was found in 123 patients and 64 negative. The groups were
      similar in average age and origin, and no significant difference was demonstrated
      for blood group. Blood group distribution between any given origin was not
      significantly different in our patients and in a sample of 182,701 blood donors.
      CONCLUSIONS: Positivity for H. pylori was not associated with blood group O. Our
      observation does not support the conclusion that the receptor for H. pylori in
      the gastric mucosa is the blood group antigen Lewis b.

PMID- 8561107
TI  - "Mother-baby" biliary endoscopy: the University of Chicago experience.
AB  - OBJECTIVE: The "mother-baby" technique of peroral cholangioscopy is a relatively
      recent development in biliary endoscopy and permits direct visualization of the
      biliary tree. This paper presents the experience of one institution with this new
      technique. METHODS: We used the Olympus mother-baby endoscopy system at the
      University of Chicago and at one of its affiliated hospitals to examine and treat
      selected lesions in the biliary tree that had eluded successful diagnosis or
      treatment by standard means. In addition, we used the baby endoscope alone
      through surgically created percutaneous tracts to treat selected patients with
      retained stones. RESULTS: From July 1990 to June 1993, peroral cholangioscopy was
      performed 18 times in 12 patients at the University of Chicago and affiliated
      hospitals. The baby endoscope was successfully passed into the bile duct in 15 of
      18 cases (83.3%). Additionally, the baby endoscope alone was used through a T
      tube or cholecystostomy tract 10 times in six patients. Complications occurred in
      two patients and were minor; there were no fatalities. With refinement of
      technique, successful passage of the baby endoscope was accomplished in 100% of
      patients undergoing peroral cholangioscopy. CONCLUSIONS: Direct visualization of
      the biliary tree with the ability to sample (brush, biopsy) or treat (basket
      removal, electrohydraulic or laser lithotripsy) lesions significantly aided in
      the care of all patients in whom the baby endoscope was successfully passed by
      providing the correct diagnosis and, when appropriate, by allowing definitive
      treatment of lesions. The eventual role of this technique in the current cost
      conscious climate is unclear, but at present it should be limited to selected
      referral centers.

PMID- 8561108
TI  - p53 Protein overexpression in colorectal tumors from patients with familial
      adenomatous polyposis: is it an early or late event?
AB  - OBJECTIVES: Tumor development is a multistep process associated with multiple
      genetic alterations. Familial adenomatous polyposis (FAP) is a classical paradigm
      to study genetic alterations in the development of colorectal neoplasms. In this
      study, we investigated the timing of p53 overexpression by immunohistochemistry
      in colorectal carcinogenesis in FAP patients and in sporadic adenomas and
      adenocarcinomas. METHODS: We examined 40 microadenomas, 114 tubular adenomas, and
      three adenocarcinomas from five FAP patients and 30 sporadic adenomas and 14
      sporadic adenocarcinomas. RESULTS: p53 overexpression was observed in 43 of 114
      adenomas with mild and moderate dysplasia and in three of three adenocarcinomas
      and in none of 40 microadenomas from FAP patients. In sporadic tumors, six of 30
      adenomas with moderate to severe dysplasia and 11 of 14 carcinomas showed p53
      overexpression. Uninvolved colonic mucosa in FAP patients, control patients, and
      patients with sporadic tumors did not stain for p53. CONCLUSIONS: These results
      indicate that p53 overexpression occurs early in the development of colorectal
      adenomas in FAP, whereas it is a late event in the development of sporadic
      tumors.

PMID- 8561109
TI  - Comparison of a rapid hepatitis B immunization schedule to the standard schedule
      for adults.
AB  - We report a prospective, randomized, single-blinded trial comparing
      immunogenicity of rapid (0, 1, and 2 months) versus standard schedule (0, 1, 6
      months) hepatitis B vaccinations of healthy adults with recombinant hepatitis B
      vaccine (Engerix-B, 20 micrograms i.m.) (230 of 234) negative to hepatitis B were
      randomized and completed the study. Groups were similar in age, weight, race, and
      obesity rate, but the rapid schedule group had more women. Both groups reached >
      or = 100 mIU/mL at a similar rate, but a higher seroprotection rate at > or = 500
      mIU/mL was reached by the standard schedule. No demographic variables influenced
      the effect of dose schedule on anti-hepatitis B titer. We conclude that rapid
      schedule vaccination gives a rate that is quicker than, and identical to, the
      rate of seroprotection of the standard schedule vaccination.

PMID- 8561110
TI  - Increased levels of human hepatocyte growth factor in serum and peritoneal fluid
      after partial hepatectomy.
AB  - OBJECTIVE/METHOD: It has been reported that inflammatory cytokines up-regulate
      human hepatocyte growth factor synthesis in vitro. To demonstrate the relation of
      this growth factor to interleukin-6 and tumor necrosis factor alpha, the changes
      in the levels of these cytokines were measured in serum and peritoneal fluid in
      22 patients after partial hepatectomy. RESULTS: Serum and fluids levels of
      cytokines showed a maximum within 3 days after surgery. Cytokines concentrations
      were much higher in fluid than in serum (p < 0.05). The maximum serum levels of
      human hepatocyte growth factor were significantly correlated with those of
      interleukin-6, intraoperative blood loss, and operating time (p < 0.05) but not
      resected liver weights. In fluid level, the growth factor was also correlated
      with interleukin-6 (p < 0.05) but with tumor necrosis factor alpha. CONCLUSIONS:
      These results suggest that human hepatocyte growth factor might be locally
      produced in the injured tissue associated with interleukin-6 and independently of
      resected liver weights.

PMID- 8561111
TI  - Clinical analysis of choledochoduodenal fistula with cholelithiasis in Taiwan:
      assessment by endoscopic retrograde cholangiopancreatography.
AB  - OBJECTIVES: Choledochoduodenal fistula (CDF) is occasionally found during
      endoscopic retrograde cholangiopancreatography (ERCP). Cholelithiasis is
      suspected to be the leading cause in some endemic areas. We focus on this cause
      of CDF to determine which clinical characteristics are relevant to formation of
      fistulas and to learn whether CDF of various types would imply different clinical
      significance. METHODS: In 1882 ERCP studies from 1988 to 1993, we found 27 CDF
      with cholelithiasis in 1066 patients. Their clinical backgrounds and ERCP
      findings were compared with those of 492 patients who had cholelithiasis but no
      CDF. RESULTS: The prevalence of CDF was 2.53%. A longer past history of biliary
      stones, recurrent biliary tract infection (BTI), and the presence of common bile
      duct stones (CBS) were factors relevant to the formation of fistula. In the case
      of 24 distal fistulas, including seven of type I and 17 of type II, there was
      concurrent distal CBS. Three cardinal features of fistula of the distal type
      were: 1) the length of CDF was less than 1.5 cm, 2) its orifice was just around
      or on the papillary fold, and 3) all cases of distal type II had prominent
      pneumobilia, less jaundice, and larger CBS than type I. Aggressive endoscopic or
      surgical treatment of distal type CDF decreased the recurrence of BTI, as
      indicated by surveillance for 1 yr. Three fistulas of the proximal type were
      longer and drained into the duodenum far from the papilla. All of these cases
      deserved early surgical intervention. CONCLUSIONS: CDF really serves as a chronic
      sequel of cholelithiasis. Different clinical features of CDF of various types
      help one to establish diagnosis and treatment. To avoid recurrence of BTI,
      aggressive therapy to correct CDF is mandatory.

PMID- 8561112
TI  - Influence of age, gender, and menstrual cycle on the normal electrogastrogram.
AB  - OBJECTIVES: Dyspeptic symptoms, which are more prevalent in females, are
      associated with gastric myoelectric and motor abnormalities. Age, gender, and
      menstrual cycle affect gastric emptying, but their effects on gastric myoelectric
      activity are not well characterized. The aim of this study was to determine the
      effects of age, gender, and menstrual cycle on gastric myoelectric activity.
      METHODS: Healthy subjects (34 male, 49 female; ages 20-79 yr) underwent cutaneous
      electrogastrography with 60-min fasting and 60-min postprandial recordings.
      Premenopausal females were studied during days 1-3, 8-10, and 18-20 after onset
      of menses. Dominant slow wave frequency (DF), power of the DF, and percent time
      the DF was in a 2- to 4-cpm rhythm were determined for fasting and postprandial
      periods. RESULTS: The DF, power of the DF, and percent time the DF was in a 2- to
      4-cpm rhythm increased from the fasting to the postprandial period. The
      postprandial increase in the DF was less in females (5.3 +/- 1.2%) than in males
      (13.0 +/- 2.6%; p < 0.01). In premenopausal females, the DF increased from
      fasting to the postprandial period for days 1-3 (6.6 +/- 1.5%; p < 0.01) and 8-10
      (6.6 +/- 2.3%; p < 0.01), but not during days 18-20 of the menstrual cycle (1.3
      +/- 1.8%). The postprandial frequency increase in DF was less for male subjects >
      or = 60 yr (3.8 +/- 4.0%) than for males < 60 yr (14.6 +/- 2.8%; p < 0.05).
      CONCLUSIONS: The DF of the electrogastrogram is affected by age, gender, and
      phase of the menstrual cycle. The influence of these factors should be recognized
      when interpreting electrogastrograms in symptomatic patients.

PMID- 8561113
TI  - Improvement of thrombocytopenia due to hypersplenism after transjugular
      intrahepatic portosystemic shunt placement in cirrhotic patients.
AB  - Thrombocytopenia secondary to hypersplenism is a well-known complication of
      portal hypertension. The effects of transjugular intrahepatic portosystemic shunt
      (TIPS) on hypersplenism have not been adequately studied. In this report, we
      describe 11 patients who had significant improvement in their thrombocytopenia
      due to hypersplenism after TIPS. There was a statistically significant
      improvement in the platelet counts after TIPS placement, in virtually every case
      during the follow-up period, although some patients had platelet counts less than
      100,000/mm3 at the end of the follow-up period. Statistically significant
      hemodynamic improvement in the gradient pressure was observed immediately after
      TIPS. Furthermore, all patients tolerated the procedure well, and TIPS-related
      complications were encountered during the follow-up period. Our data suggest that
      TIPS is an effective, noninvasive alternative to surgical interventions in the
      management of hypersplenism in cirrhotic patients, who are generally high-risk
      surgical candidates.

PMID- 8561114
TI  - Glomerulonephritis associated with acute hepatitis B.
AB  - Acute hepatitis B virus (HBV) infection has very rarely been associated with
      glomerulonephritis. We describe a case of post-infections glomerulonephritis
      associated with acute HBV infection. The kidney disease resolved concomitantly
      with the hepatitis, and the patient recovered from acute HBV infection.

PMID- 8561115
TI  - Diagnosis by routine scintigraphy of hepatic reticuloendothelial failure before
      severe liver dysfunction.
AB  - OBJECTIVES: The prognosis of hepatic reticuloendothelial failure is said to be
      poor. Scanning with the radiocolloid 99mTc phytate is needed for diagnosis; as a
      rule; only seriously ill patients are so investigated. We use 99mTc phytate for
      liver scans of almost all inpatients with liver disease. This routine made
      diagnosis of a mild form or early stage of the disease possible. We evaluated the
      clinical findings of the five patients we have diagnosed, in an attempt to find
      why four survived. METHODS: Radiocolloid scans were taken starting 20-30 min
      after the intravenous injection of 111 MBq of 99mTc phytate. Hepatobiliary images
      were taken by use of 99mTc pyridoxylidine-5-methyl trytophan, and hepatic
      receptor images were taken by use of 99mTc-labeled diethylenetriaminepentaacetic
      acid coupled with galactosyl human serum albumin. RESULTS: The livers were not
      visible in the radiocolloid scans, so the diagnosis of hepatic
      reticuloendothelial failure was considered. In the two other imaging
      examinations, the livers were visible. The cause was identified as heavy alcohol
      intake in four cases and toluene hepatotoxicity in one case. Histological
      examinations showed cirrhosis in two patients; the three other patients did not
      have cirrhosis. All five patients had anemia, and three had infections. One
      patient died of multiple organ failure, and the four other patients survived.
      Long-term observation by radiocolloid scanning was possible in one patient in
      whom radionuclide uptake into the liver rose as hepatic function improved.
      CONCLUSIONS: This disorder is associated with a temporary decrease in Kupffer
      cell function and hence is liable to be complicated by infection, which can
      result in death. If the cause is removed promptly, recovery is likely. There
      being a mild form of this disease, previously not generally diagnosed, probably
      accounts for the outcomes being good in all of our patients except the one
      patient with severe liver dysfunction at the time of diagnosis.

PMID- 8561116
TI  - Low-amplitude distal esophageal spasm as a cause of severe dysphagia for solid
      food.
AB  - This case report presents a patient with progressive dysphagia, accompanied by
      weight loss, in the absence of organic disease. Esophageal motility studies
      initially failed to reveal a diagnosis. At simultaneous manometry and
      fluoroscopy, with bread/barium boluses, the diagnosis of esophageal spasm in a
      relatively weak esophagus was made. All conservative treatment modalities failed.
      Thoracoscopic myotomy resulted in partial field of symptoms. Finally, an
      esophagectomy was performed because of sever dysphagia accompanied by persisting
      weight loss.

PMID- 8561117
TI  - Pancreatic duct stricture caused by islet cell tumors.
AB  - We report three cases of pancreatic islet cell tumors causing stricture of the
      main pancreatic duct. The clinical presentation was consistent with episodes of
      acute pancreatitis or biliary colic. One patient in whom the diagnosis was
      delayed died of metastatic disease. Islet cell tumors are an important clinical
      entity that must be considered in the differential diagnosis of pancreatic duct
      strictures.

PMID- 8561118
TI  - Conservative management of esophageal nontransmural tears after pneumatic
      dilation for achalasia.
AB  - OBJECTIVE: We sought to determine the incidence and outcome with conservative
      management of esophageal nontransmural tears after pneumatic dilation for
      achalasia. METHODS: Retrospective review of 50 pneumatic balloon dilations in 30
      patients with achalasia was performed at one center over an 18-month period.
      RESULTS: Forty-four of 50 procedures (88%) were performed without complication.
      Two patients (4%) developed transmural perforations requiring immediate surgical
      repair; both recovered uneventfully. Four patients (8%) were found to have linear
      mucosal tears on routine postprocedure esophagrams. One patient was asymptomatic,
      and three had chest pain. No patient had fever. These four patients were managed
      conservatively with in-hospital observation for a mean of 4.3 days (range 3-6):
      nothing by mouth for a mean of 1.3 days (range 1-2) and i.v. antibiotics for a
      mean of 3 days (range 2-5). All were discharged within 6 days and were
      asymptomatic and tolerating a regular diet. CONCLUSIONS: Esophageal nontransmural
      tears are not uncommon after pneumatic dilation for achalasia and can be safely
      treated with conservative medical management.

PMID- 8561119
TI  - Disappearance of the pseudo-cholangiocarcinoma sign after TIPSS.
AB  - Bile duct varices, also named the "pseudo-cholangio- carcinoma sign<" are
      frequently encountered by ERCP in portal hypertension cases due to cavernous
      transformation of the portal vein. There is a documentation that, in three cases,
      this sign disappeared after placement of a transjugular intrahepatic
      portosystemic shunt.

PMID- 8561120
TI  - Obstructive jaundice due to multiple hepatic peribiliary cysts.

PMID- 8561121
TI  - Severe hyperbilirubinemia due to acute hepatitis A superimposed on a chronic
      hepatitis B carrier with glucose-6-phosphate dehydrogenase deficiency.
AB  - Taiwan is an endemic area for hepatitis A and B virus infections; nearly 90% of
      adults have serological markers for either virus. Glucose-6-phosphate
      dehydrogenase (G6PD) deficiency is also common, ranging from 2% to 10%. We report
      the case of a 36-yr-old chronic HBV male carrier with G6PD deficiency who
      developed acute viral hepatitis A with severe hyperbilirubinemia and
      intravascular hemolysis. The hemolysis was in all likelihood the result of recent
      exposure to sulfa drugs. Fulminant hepatitis was the initial impression, because
      the peak serum total bilirubin concentration was alarmingly high, at 85.4 mg/dl.
      Exchange plasmapheresis was fresh frozen plasma was performed, and various
      laboratory studies gradually returned to near normal laboratory studies gradually
      returned to near normal over the next 3 wk. The patient made an uneventful
      recovery 1 month after admission.

PMID- 8561122
TI  - A case of hemobilia after percutaneous liver biopsy treated by transcatheter
      arterial embolization with Histoacryl.

PMID- 8561123
TI  - A case of Trichuris trichiura infection diagnosed by colonoscopy.
AB  - A 65-year-old Japanese female was admitted to our hospital because of right lower
      abdominal pain. Laboratory and roentgenological tests revealed no abnormalities.
      Repeated stool examinations revealed no ovum or parasite. However, colonoscopic
      examination demonstrated the presence of a parasite on the edematous mucosa of
      cecum. The adult male whipworm (Trichuris trichiura) was then removed
      endoscopically. Her symptoms disappeared quickly, and no additional parasite was
      found in the feces during or after the mebendazole treatment. Repeated stool
      examinations failed to show any ova, because this patient was infected by a
      single male parasite. Colonoscopic study should be considered a useful tool for
      the diagnosis of T. trichiura infection, even if no ovum is found in stool
      examination.

PMID- 8561124
TI  - A rare case of multiple intussusceptions: intense segmentary lipomatosis of the
      ileum.
AB  - We report a patient who presented with intestinal obstruction; his small
      intestine showed intense segmentary lipomatosis associated with unusually
      situated multiple intussusceptions. Preoperatively, we diagnosed intussusceptions
      in the ileocecal region by ultrasonography and computed tomographic scan. During
      surgery, the ileum was dilated and contained numerous movable polypoid masses.
      One reducible intussusception was encountered in the ileocecal region. In
      addition, an ileoileal intussusception that could not be reduced was resected
      with an end-to-end anastomosis. At histological examination, more than 150
      submucosal lipomas were found.

PMID- 8561125
TI  - Portal and mesenteric thrombosis in protein S (pS) deficiency.
AB  - Portal and/or mesenteric thrombosis is a rare occurrence, and often an underlying
      hypercoagulable state can be found. We describe a case in which a mesenteric
      infarction due to mesenteric venous thrombosis occurred as the first
      manifestation of an inherited type I deficiency of protein S, whereas signs of
      portal thrombosis emerged later.

PMID- 8561126
TI  - Subacute mitochondrial liver disease in a patient with AIDS: possible
      relationship to prolonged fluconazole administration.
AB  - Azole-derived antifungal medications are particularly involved in drug-induced
      hepatic injury encountered in patients with AIDS. Fluconazole may induce multiple
      hepatic abnormalities usually characterized by asymptomatic and reversible mild
      hepatic necrosis. We here describe severe subacute liver damage occurring in a
      patient with AIDS who was receiving fluconazole maintenance therapy for a
      cryptococcosis. Hepatotoxicity was essentially characterized by mixed cytolytic
      and cholestatic liver tests abnormalities which improved after fluconazole
      discontinuation and worsened on fluconazole rechallenge. Optical microscopy
      demonstrated nonspecific abnormalities including granular aspect of the cytoplasm
      of the hepatocytes. In contrast, analysis of electron microscopy revealed unusual
      unreported features characterized by giant mitochondria with paracrystalline
      inclusions and enlarged smooth endoplasmic reticulum. All microscopic
      abnormalities were reversed after discontinuation of fluconazole. We suggest that
      persistent increased hepatic enzymes in HIV-infected patient taking fluconazole
      should prompt suspension of the treatment. Prospective studies are needed to
      determine whether careful monitoring of hepatic tests should be recommended in
      AIDS patients on prolonged fluconazole maintenance therapy.

PMID- 8561127
TI  - Cytomegalovirus colitis mimicking colon carcinoma in an HIV-negative patient with
      chronic renal failure.
AB  - Cytomegalovirus (CMV) colitis is thought to occur almost exclusively in
      immunosuppressed persons. Colonoscopy in patients with CMV colitis usually shows
      diffuse or localized ulceration, although mucosal friability, erosions,
      hemorrhage, and plaque-like pseudomembranes may be observed. We report on a
      patient with chronic renal failure undergoing hemodialysis therapy who had
      abdominal symptoms, including bloody diarrhea, along with colonoscopic findings
      suggestive of carcinoma of the colon. The patient was not infected with the human
      immunodeficiency virus and had normal lymphocyte subset numbers. He was
      subsequently found to have invasive CMV disease of the colon. CMV colitis can
      occur in persons who are not severely immunosuppressed, and its colonoscopic
      appearance may mimic that of colon cancer.

PMID- 8561128
TI  - Polio and small pox: diseases of historical interest because of vaccines. Will
      this also apply to Helicobacter pylori?

PMID- 8561129
TI  - Bile reflux in Barrett's esophagus: the chicken or the egg?

PMID- 8561130
TI  - Re: Evaluation of new therapy for eradication of H. pylori infection in nude
      mouse model.

PMID- 8561131
TI  - Re: [13C]urea breath test for Helicobacter pylori infection.

PMID- 8561132
TI  - Response to article by Forne et al.

PMID- 8561133
TI  - Endoscopic appearance of colonic lymphoid nodules.

PMID- 8561134
TI  - Fatal complications after placement of an esophageal self-expanding metal stent.

PMID- 8561135
TI  - Colchicine in the treatment of hepatic fibrosis in children.

PMID- 8561136
TI  - Primary rectal Hodgkin's lymphoma: initial manifestation of HIV.

PMID- 8561137
TI  - Constipation in an elderly community: a study of prevalence and potential risk
      factors.
AB  - OBJECTIVE: The epidemiology of chronic constipation in the elderly remains poorly
      defined. We aimed to study the prevalence of, and potential risk factors for,
      constipation in a representative elderly community, using symptom-based
      diagnostic criteria. METHODS: An age and gender-stratified random sample of 1833
      eligible residents of Olmsted County, Minnesota, aged 65 yr and over, was mailed
      a valid self-report questionnaire; 1375 responded (75%). RESULTS: The overall age
      and gender-adjusted prevalence (per 100) of any constipation was 40.1 (95% CI
      38.9, 44.4); for functional constipation and outlet difficulty or delay, the
      prevalence rates were 24.4 (95% CI 22.0-26.9) and 20.5 (95% CI 18.2-22.8),
      respectively. Self-reported constipation did not reliably identify functional
      constipation or outlet delay. Outlet delay, but not functional constipation, was
      more frequent in women; functional constipation, but not outlet delay, was
      associated with advancing age. Nonsteroidal anti-inflammatory drugs and other
      medications were significant risk factors in subjects with functional
      constipation and outlet delay combined. CONCLUSIONS: In independently living,
      elderly persons, constipation is a common complaint; among these subjects, there
      appear to be symptom subgroups that can be identified.

PMID- 8561138
TI  - An examination of the reliability of reported stool frequency in the diagnosis of
      idiopathic constipation.
AB  - OBJECTIVES: To investigate the reliability of reported stool frequency in the
      diagnosis of constipation. METHODS: Our criterion for the diagnosis of idiopathic
      constipation was < or = 3 stools per week for > or = 6 months. Subjects who
      believed that they met this criterion were invited to participate. Daily stool
      frequency was recorded over a 4-wk period, and all stools were weighed during the
      final week. A colon transit study and anorectal manometry were performed at the
      beginning and at the end of the study. RESULTS: On review of stool diaries from
      45 subjects who described chronic constipation and who completed the 4-wk study,
      only 22 (49%) actually satisfied our criterion for idiopathic constipation. The
      remaining 23 (51%) subjects, although describing constipation, had, on average, 6
      stools/wk. A history of psychiatric illness was 5 times more frequent among those
      whose bowel symptoms correlated poorly with objective measures. Measures of
      difficult defecation were similar in the two groups. Mean colon transit time was
      significantly longer and correlated closely with stool weight only in subjects
      who truly were constipated (p < 0.05). Anorectal manometry was not helpful in
      discriminating between those who satisfied our criterion for constipation and
      those who did not. CONCLUSIONS: Defining constipation on the basis of a patient's
      reported stool frequency may prove misleading; the diagnosis of idiopathic
      constipation should be supported by the use of stool diaries and a colon transit
      study.

PMID- 8561139
TI  - Stalking the guardian of the genome: p53 in colorectal carcinogenesis.

PMID- 8561140
TI  - Epidemiology of fecal incontinence: the silent affliction.
AB  - OBJECTIVE: Fecal incontinence represents an embarrassing social problem, the
      magnitude of which remains largely unknown. The present study prospectively
      examined the prevalence and demographic distributions of fecal incontinence.
      METHODS: demographic data, in addition to information regarding the reason for
      visit, bowel habits, and the frequency, type, and severity of fecal incontinence,
      were collected from individuals at the time of visits to their primary care
      physician or gastroenterologist. RESULTS: Eight hundred and eighty-one
      individuals 18 yr or older were included in the analysis. The overall prevalence
      of fecal incontinence was 18.4%. When stratified by frequency, 2.7, 4.5, and 7.1%
      of participants admitted to incontinence daily, weekly, or once per month or
      less, respectively. Incontinence increased progressively with age and was 1.3
      times more common in males than females. Only one-third of individuals with fecal
      incontinence had ever discussed the problem with a physician. CONCLUSIONS: The
      prevalence of fecal incontinence appears to be more common than previously
      appreciated. Moreover, only a minority with a physician. It would seem important
      to more actively pursue this "silent affliction" particularly in patients who do
      not readily volunteer this information.

PMID- 8561141
TI  - Clinical response does not correlate with intestinal or blood cyclosporine
      concentrations in patients with Crohn's disease treated with high-dose oral
      cyclosporine.
AB  - OBJECTIVE: High-dose ( >5 mg/kg/d) oral cyclosporine may be effective treatment
      for Crohn's disease, whereas low-dose oral cyclosporine ( < or = 5 mg/kg/d) is
      not. This study determined the correlation between blood and intestinal tissue
      cyclosporine concentrations and clinical response in patients with Crohn's
      disease treated with cyclosporine 8 mg/kg/day. METHODS: Twelve patients with
      inflammatory Crohn's disease were treated for 6 wk with oral cyclosporine 8
      mg/kg/day, adjusted to a whole blood cyclosporine concentration (chromatography)
      of 200-300 ng/ml. Response was determined by the Crohn's disease activity index.
      Cyclosporine was measured in intestinal tissue biopsies obtained by colonoscopy
      at week 6 (chromatography). RESULTS: Eight patients responded and four did not
      respond. There were no significant differences between the responders and
      nonresponders in the mean whole blood or intestinal tissue cyclosporine
      concentrations. Similarly, there were no significant correlations between change
      in the Crohn's disease activity index score (baseline to week 6) and whole blood
      or intestinal tissue cyclosporine concentrations. Cyclosporine side effects,
      including nephrotoxicity and peroneal nerve palsy, were common. CONCLUSIONS:
      Clinical response did not correlate with whole blood or intestinal tissue
      cyclosporine concentrations in patients treated with high-dose cyclosporine for
      Crohn's disease. Cyclosporine side effects, including a significant decrease in
      renal function, were common.

PMID- 8561142
TI  - Risk factors of colorectal cancer in inflammatory bowel disease.
AB  - BACKGROUND: It is unknown whether colorectal cancer (CRC) in patients with
      inflammatory bowel disease (IBD) behaves differently from regular CRC in patients
      without IBD. A case-control study was conducted to compare CRC in patients with
      and without underlying IBD. METHODS: The Department of Veterans Affairs (VA)
      maintains a computerized file of all hospital discharges among U.S. military
      veterans since 1970. This file accrues the data of 1 million hospital discharges
      per year. All patients with IBD and all patients with CRC who had been discharged
      from a VA hospital between 1981 and 1993 were selected. The influence of various
      risk factors on the occurrence of CRC in IBD and its mortality in patients with
      and without IBD was tested by logistical regression analyses. RESULTS: Of the
      11,446 subjects with IBD, 371 had colon cancer. CRC was diagnosed in 52,243
      subjects without IBD. CRC patients with IBD were 7 yr younger than those without
      IBD, but in patients with Crohn's disease, more cancers were located in the
      proximal colon (chi 2 = 18.10, df = 5, p = 0.003). The occurrence of CRC in IBD
      was influenced by the following risk factors: age [odds ratio (OR) = 1.45, 95%
      confidence interval (CI) = 1.35-1.57], sclerosing cholangitis (OR) = 3.41, CI =
      2.03-5.73), and history of a disease associated with consumption of nonsteroidal
      anti-inflammatory drugs (NSAID) (OR = 0.84, CI = 0.65-1.09). Sex, race, and type
      of IBD did not exert a significant influence on the development of cancer. Cancer
      related mortality was influenced by the following risk factors: age (OR = 1.16,
      CI = 1.14-1.18), male gender (OR = 1.23, CI = 1.06-1.44), white race (OR) = 0.97,
      CI = 0.96-0.99), and history of NSAID consumption (OR = 0.68, CI = 0.65-0.72).
      Presence of IBD was not associated with a significant influence on CRC mortality
      (OR = 1.00, CI = 0.70-1.43). CONCLUSIONS: CRC affects IBD patients at a younger
      age and is characterized by a more proximal localization when compared with CRC
      of non-IBD patients. NSAID exert a protective influence against CRC in patients
      with IBD similarly as in patients without IBD. Sclerosing cholangitis is
      associated with a strong risk of developing colon cancer in patients with IBD.

PMID- 8561143
TI  - The prognostic value of preoperative serum levels of CEA and CA19-9 in patients
      with gastric cancer.
AB  - OBJECTIVES: The clinical significance of preoperative serum levels of tumor
      markers CEA and CA19-9 was evaluated in gastric cancer patients. METHODS: Serum
      levels of CEA and CA19-9 were measured in 663 patients with gastric cancer who
      underwent laparotomies over a recent 4-yr period (1990-1993). The correlations
      between the serum levels of tumor markers and several clinicopathological factors
      were evaluated by univariate analysis. The significance of the tumor markers as
      prognostic factors was assessed by multivariate analysis. RESULTS: The positivity
      rates of CEA and CA19-9 were 16.6% and 16.0%, respectively. The positivity of CEA
      correlated well with the sex of the patients, hepatic, peritoneal, and nodal
      metastases and the depths of tumors, but it correlated weakly with a tumor's
      histological type. The positivity of CA19-9 correlated well with various forms of
      metastases, depths, and tumor size. A significant in prognosis was observed
      between patients positive and negative for CA19-9 among those undergoing R0
      resection. Multivariate analysis also revealed that serum CA19-9 was better than
      CEA as a prognostic factor. CONCLUSIONS: CA19-9 in the preoperative sera is a
      good prognostic factor in gastric cancer patients, although tumor markers
      continue to have only limited diagnostic usefulness.

PMID- 8561144
TI  - The effect of posture on gastroesophageal reflux event frequency and composition
      during fasting.
AB  - OBJECTIVE: To examine the influence of three postures (upright and left and right
      recumbent) on gastroesophageal reflux event (RE) frequency and composition and a
      possible mechanism for the observations. METHODS: A) Forty fasting patients with
      (E+, n = 20) and without (E-, n =20) esophagitis were studied. Simultaneous
      manometry and pH monitoring were conducted in the left and right recumbent (10
      min each) as well as the upright posture (20 min). RE were classified by the pH
      probe and/or the manometry catheter as acid or gas RE. B) In 23 patients referred
      for UGI series, radiographs were taken in the left and right recumbent and
      upright postures after barium and Fizzies. RESULTS: A) Upright RE were similar in
      frequency in E+ and E- patients (2.6 +/- 0.5 vs 3.05 +/- 0.6). However, E+
      patients had more recumbent RE (16.3 +/- 3 vs 0.65 +/- 0.2, p = 0.0001) than E-
      patients; moreover, the left recumbent posture had more recumbent RE than the
      right (10.9 +/- 2 vs 5.3 +/- 1, p < 0.02). Moving from recumbent to the upright
      posture had an opposite effect on RE in the two groups; RE decreased sixfold in
      E+ patients (16.3 +/- 3 vs 2.6 +/- 0.5, p = 0.0001) but increased fourfold in E-
      patients (0.65 +/- 0.2 vs 3.05 +/- 0.6, p = 0.0001). In examining RE composition
      in the E+ patients, RE were twofold more likely to be gas in the left recumbent
      posture (7.6 +/- 2 vs 3.3 +/- 1, p < 0.1); in direct contrast, RE were eightfold
      more likely to be acid in the right recumbent posture (4.7 +/- 1 vs 0.6 +/- 0.5,
      p = 0.0001). As expected from this observation, acid exposure was greater in the
      right than left posture (52 +/- 8 vs 15 +/- 6%, p < 0.0001). Although RE were too
      infrequent in E- patients to reach statistical significance, the effect of
      posture on the composition of the few RE that did occur mirrored that of the E+
      patients. B) In 17/23 (74%) radiographs in the right recumbent posture, the EG
      junction was submerged in a barium pool below the air-barium interface in the
      stomach. In contrast, this occurred in 0/23 patients in the left recumbent and
      1/23 patients in the upright postures because the EG junction was in the air
      above the barium pool. CONCLUSION: Posture has an influence on RE frequency and
      composition while fasting, and the latter is likely due to whether the EG
      junction is submerged below liquid gastric contents or in the air above the
      liquid gastric contents.

PMID- 8561145
TI  - Correlation of lower esophageal mucosal ring and 24-h pH monitoring of the
      esophagus.
AB  - OBJECTIVE: To study the relationship of LEMR and gastroesophageal reflux. The
      pathogenesis of the lower esophageal mucosal ring (LEMR) is not known. The most
      likely theory is that the ring results from reflux esophagitis as part of the
      morphological spectrum of peptic stricture. METHODS: We correlated barium
      esophagrams and 24-h pH monitoring (pHM) in 343 patients (173 women, 170 men;
      mean age 52 yr). Patients were categorized into three groups by radiographic
      findings: 1) normal esophagus (n = 121), 2) hiatal hernia (HH) only (n = 174),
      and 3) LEMR (n =48). Abnormal pHM was defined as a total percentage of the
      esophageal acid exposure time of 6% or more; abnormal pHM was also analyzed
      relative to patient position (supine vs. upright). RESULTS: Findings showed that
      21 (17%) of 121 normal patients had abnormal pHM compared with 58 (33%) of 174
      patients with HH and 15 (31%) of 48 patients with LEMR. Normal patients had a
      significantly lower frequency of abnormal pHM (p < 0.01) vs. the other two
      groups; however, no significant difference in results of pHM was found in the
      groups with HH and LEMR. No significant relationships of abnormal supine versus
      upright pHM was observed comparing the three groups. CONCLUSIONS: 1) Most
      patients in this study had normal pHM, regardless of the anatomic status of the
      esophagogastric region; 2) patients with HH and LEMR had a higher frequency of
      abnormal pHM, although the two groups were not significantly different; and 3) an
      etiological relationship of LEMR and gastroesophageal reflux was not supported,
      other than its association with HH.

PMID- 8561146
TI  - Esophageal mucosal eicosanoids in gastroesophageal reflux disease and Barrett's
      esophagus.
AB  - OBJECTIVE: Eicosanoids (prostaglandins and leukotrienes) may contribute to the
      clinical manifestations of gastroesophageal reflux disease (GERD). In this cross
      sectional study, our purpose was to assess the role of leukotriene B4 (LTB4) and
      prostaglandin E2 (PGE2) in the clinical, endoscopic, and histological
      manifestations of GERD. METHODS: Using RIA, we measured ex vivo LTB4 and PGE2
      content in esophageal mucosal biopsies from 141 patients with or without
      gastroesophageal reflux disease who underwent upper endoscopy. Patients were
      classified as normal symptomatic controls(n = 70), esophagitis stages 1-4 (n =
      60), and Barrett's esophagus (n = 11), using clinical, endoscopic, histological,
      manometric, and esophageal 24-h ambulatory pH criteria. RESULTS: Mean LTB4 levels
      were significantly higher in both endoscopically and histologically identified
      erosive esophagitis and Barrett's esophagus patients, compared with normal
      controls. In contrast, PGE2 levels did not differ significantly among endoscopic
      or histological groups. When eicosanoid levels and composite symptom score
      (frequency score x severity score summed over five symptoms) were analyzed, no
      significant associations were found between LTB4 or PGE2 levels and the composite
      symptom score. There was no correlation between tissue eicosanoid levels and
      either the degree of esophageal acid exposure by ambulatory pH monitoring or the
      lower esophageal sphincter resting pressure as assessed by esophageal motility.
      Treatment with omeprazole 20 mg by mouth daily for 6 wk significantly reduced
      both LTB4 and PGE2 levels (p < 0.05) and was associated with significant
      improvement of symptoms and the endoscopic and histological appearance of the
      esophagus in 25 patients. CONCLUSIONS: These results suggest that LTB4, a
      prominent product of arachidonic acid metabolism in neutrophils, mediates the
      inflammatory phenomena of reflux esophagitis. The role of LTB4 and PGE2 in the
      induction of symptoms in patients with GERD and Barrett's esophagus remains
      unclear.

PMID- 8561147
TI  - Prevalence of oral lesions in inflammatory bowel disease.
AB  - OBJECTIVE: To obtain precise data on the prevalence of oral lesions in
      inflammatory bowel disease (IBD). METHODS: Oral lesions were carefully sought in
      a consecutive series of 198 Italian IBD outpatients, 77 with Crohn's disease (CD)
      and 121 with ulcerative colitis (UC); 89 subjects with functional intestinal
      motility disorders served as controls. RESULTS: The oral lesions detected were
      angular cheilitis (in 7.8% of CD patients, 5% of UC patients, and 0% of controls
      (p < 0.05, patients vs controls), lichen (6.5, 5.8, and 3.3%, respectively, p =
      not significant), aphthous ulcers (5.2, 5.8, and 5.6%, respectively, p = not
      significant), candidiasis (5.2, 0.8, and 0%, respectively, p < 0.05, CD patients
      vs controls), benign tumors (5.2, 0, and 7.8%, respectively, p < 0.05, patients
      vs controls), leukoplakia (5.2, 11, and 3.3%, respectively, p = not significant),
      and, less frequently, glossitis and herpes labialis. No specific CD oral lesions
      were observed in this series. No correlation was found between clinical disease
      activity and frequency of oral lesions. CONCLUSIONS: Aphthous ulcers are not
      common in IBD patients. Oral candidiasis is more frequent in CD than UC patients
      and controls.

PMID- 8561148
TI  - Relationship between gastroesophageal reflux and gastric emptying after distal
      gastrectomy.
AB  - OBJECTIVES: Our objective was to determine whether delayed gastric emptying
      contributes to gastroesophageal reflux after distal gastrectomy. METHODS: To
      study gastric emptying and gastroesophageal reflux, we used a tecnnetium-labeled
      mixed liquid and solid test meal in 46 distal gastrectomy patients (19 with
      reflux symptoms and 27 without) and in 10 controls. The relationship of reflux
      symptoms to gastric emptying and the correlation between gastric emptying and the
      scintigraphic reflux index were evaluated. RESULTS: The reflux index was
      significantly higher in the symptomatic group (9.76 +/- 5.64%) than in the
      asymptomatic group (4.45 +/- 2.70%). The gastric emptying half time was
      significantly longer in the symptomatic group (53.13 +/- 19.39 min) than in
      asymptomatic group (34.26 +/- 20.40 min) and in normal controls (27.31 +/- 4.60
      min). There was a significant linear correlation between the scintigraphic reflux
      index and the gastric emptying half time (r = 0.505,p < 0.001). CONCLUSIONS:
      These findings suggest that scintigraphy is a reasonably accurate test for
      detecting gastroesophageal reflux and that delayed gastric emptying plays an
      important role in the development of reflux after distal gastrectomy.

PMID- 8561149
TI  - A predictive model to identify Clostridium difficile toxin in hospitalized
      patients with diarrhea.
AB  - OBJECTIVES: Although Clostridium difficile is a common pathogen in hospitalized
      patients with diarrhea, no study has attempted to develop a predictive model to
      estimate the likelihood of C. difficile positivity. METHODS: We conducted a cross
      sectional study at a single hospital of 271 patients with diarrhea for whom stool
      was tested for C. difficile toxin. The sample was randomly divided into a subset
      to derive the model (n = 180) and another to validate it (n =91), and independent
      predictors of toxin positivity were identified using logistical regression
      analysis. RESULTS: C. difficile toxin was present in 81 patients and absent in
      190. In the derivation set, a positive toxin was independently predicted (p <
      0.0005) by readmission within 2 wk of prior hospitalization, by a white blood
      cell count > or = 10,000/mm3, and by presence of fecal leukocytes. In the
      validation set, C. difficile toxin was present in 24, 29, and 77% of patients
      with 0, 1, and > or = 2 risk factors, respectively. CONCLUSION: If validated
      prospectively and/or other centers, the model could identify patients who should
      be considered for empirical management while awaiting results of toxin assays.

PMID- 8561150
TI  - Long-term follow-up of Helicobacter pylori serology after successful eradication.
AB  - OBJECTIVE: To determine the Helicobacter pylori IgG serology pattern 12-21 months
      after successful organism eradication and to assess the usefulness of IgG
      serology in the long-term follow-up of patients. METHODS: We recruited patients
      from our 1990-91 study on IgG serology after H. pylori treatment. Forty-three of
      45 patients (93%) agreed to participate. They had all been cured of H. pylori
      infection after triple antibiotic therapy and remained H. pylori negative at 1 yr
      posttreatment. H. pylori IgG antibody concentrations were measured in serum
      samples taken at 3-month intervals between 12 and 21 months posttreatment. [13C]
      urea breath test was done at each blood draw to ensure continued eradication.
      Serology was determined by ELISA (Pylori Stat, BioWhittaker, Inc) and expressed
      as absorbance. RESULTS: All 43 patients (100%) continued to be free of H. pylori
      and demonstrated a decline in their H. pylori IgG concentration compared with
      baseline. The overall decline in serology among all 43 patients was approximately
      50%. Forty of 43 patients (93%) had a decline of more than 20% in H. pylori IgG
      concentration compared with baseline. However, 28 of 43 patients (65%) remained
      seropositive for more than 1 yr after successful H. pylori eradication.
      CONCLUSION: We conclude that a 20% decline in IgG concentration has an overall
      sensitivity of 93% for determining H. pylori eradication 12-21 months after H.
      pylori treatment. Serology is an attractive alternative to endoscopy or urea
      breath tests in monitoring patients after H. pylori treatment, but serum IgG
      levels should not be expected to reach seronegative range after successful H.
      pylori eradication.

PMID- 8561151
TI  - Prolonged effect of omeprazole on the 14C-urea breath test.
AB  - OBJECTIVES: We investigated omeprazole's effect on 14C-urea breath testing. We
      also determined the duration of omeprazole's effect on the breath test. Finally,
      we studied whether effects on breath testing were dose dependent. METHODS: Fifty
      seven employees and outpatients were screened for Helicobactor infection. Those
      positive for serology, CLO, or histology were asked to undergo baseline breath
      testing. Those with a positive breath test took omeprazole 20 mg/day for 14 days
      followed by repeat breath testing, 1, 3, and 5 days after therapy. Subjects with
      persistently positive breath tests despite omeprazole 20 mg/day were asked to
      take omeprazole 20 mg b.i.d. for 14 days. Repeat breath tests were performed as
      above. RESULTS: Thirteen of 57 had HP infection. Ten of 13 underwent a baseline
      breath test. Eight of 10 with baseline breath test experienced a significant
      decrease in expired 14CO2 after omeprazole 20 mg/day. Five of 13 with active HP
      infection developed a negative breath test after omeprazole. All subjects had a
      positive breath test within 5 days of stopping omeprazole 20 mg/day. Five of
      eight with persistently positive breath tests despite omeprazole 20 mg/day took
      omeprazole 40 mg/day. Four of five developed a significant decrease in 14CO2
      excretion after omeprazole. All subjects had a positive breath test within 5 days
      of stopping omeprazole 40 mg/day. CONCLUSIONS: Recent treatment with omeprazole
      20 mg/day led to a false-negative breath tests in 38.5%. This effect appeared to
      be dose dependent and lasted up to 5 days after cessation of omeprazole.

PMID- 8561152
TI  - Triple therapy vs. amoxicillin plus omeprazole for treatment of Helicobacter
      pylori infection: a multicenter, prospective, randomized, controlled study of
      efficacy and side effects.
AB  - OBJECTIVE: this study compares the efficacy and side effects of the two commonly
      used treatment regimens for Helicobacter pylori infection. METHODS: 118 patients
      with culture-proven H. pylori infection (61 with duodenal ulcer, 19 with gastric
      ulcer, three with both duodenal and gastric ulcer, and 35 with non-ulcer
      dyspepsia) were randomized to receive either triple therapy (tetracycline 250 mg,
      metronidazole 250 mg, colloidal bismuth subcitrate 120 mg, four times daily) for
      14 days or amoxicillin 1000 mg and omeprazole 40 mg both twice daily for 14 days.
      The isolated H. pylori strain was metronidazole susceptible in 93%. Antral biopsy
      samples were taken for culture, urease testing, histology and, in most patients,
      for PCR at least 6 wk after treatment. A separate corpus sample was taken for
      culture. Eradication was defined as the absence of H. pylori in all specimens. In
      seven cases, when only histology was doubtfully positive, and all other tests
      including PCR were negative, a 13C-urea breath test was performed, the result of
      which was recorded by the patient on a semi-quantitative scale. RESULTS: H.
      pylori was eradicated by triple therapy in 96.3% and by amoxicillin/omeprazole in
      77.2% of the patients (p = 0.008). Side effects occurred more often with triple
      therapy (72.7% vs. 50.8%; p< 0.05) but were mild in most cases. Severe side
      effects occurred equally in both treatment groups. CONCLUSIONS: When the
      prevalence of metronidazole resistance is low, triple therapy is more effective
      than amoxicillin/omeprazole. Side effects occur more often in triple therapy but
      are mild in most cases.

PMID- 8561153
TI  - Cure of Helicobacter pylori infection: role of duration of treatment with
      omeprazole and amoxicillin.
AB  - OBJECTIVES: To date, some studies have suggested that short-term therapy may be a
      promising therapeutic concept for the eradication of Helicobacter pylori. The
      primary objective of the present study was to elucidate the role of the duration
      of treatment in the cure of H. pylori infection. METHODS: Forty consecutive
      patients with H. pylori-positive peptic ulcer disease were randomly allocated to
      four study groups. The groups were treated with a 14-day course of 20 mg
      omeprazole b.i.d. orally combined with 2 g amoxicillin t.i.d. intravenously for 1
      day (n = 10; six women, age range 40-84 yr), for 3 days (n = 10; five women, age
      range 29-74 yr), for 5 days (n = 10; five women, age range 21-82 yr), for 7 days
      (n = 10); five women, age 42-82 yr), respectively. Initially, a standardized
      clinical evaluation of symptoms and and upper GI tract endoscopy were performed
      for assessment of H. pylori infection of the gastric mucosa (biopsy urease test,
      specific culture, and histology). At least 4 wk after cessation of omeprazole
      medication, H. pylori eradication was evaluated either as described or with the
      help of the 13C-urea breath test. RESULTS: H. pylori eradication, defined as
      negative bacterial findings in urease test, culture, and histology or 13C-urea
      breath test at least 4 wk after discontinuation of omeprazole therapy, was
      achieved in one of 10 patients (10%) in the one-day group, none of 10 patients
      (0%) in the 3- and 5-day groups and six of 10 patients (60%) in the 7-day group.
      CONCLUSION: We conclude that short-term therapies with the proton pump inhibitor
      omeprazole and the antibiotic amoxicillin must be considered completely
      ineffective if performed as a short-term therapy for up to 5 days. A therapy
      duration of 7 days seems to mark a turning point in antibiotic effectiveness,
      with a rapid increase in eradication rates.

PMID- 8561154
TI  - Exercise, employment, other daily activities, and adverse pregnancy outcomes.
AB  - The relations of exercise, employment, and other daily activities during
      pregnancy with pregnancy outcomes were examined using data from the Missouri
      Maternal and Infant Health Survey. Maternal surveys were available for the
      following singleton birth categories: 450 fetal deaths; 782 very low birth weight
      (VLBW, < 1,500 g); 802 moderately low birth weight (MLBW, 1,500-2,499 g); and 794
      normal birth weight (NBW, > or = 2,500 g). All mothers were Missouri residents at
      the time of their December 1989 to March 1991 deliveries. It was found that VLBW
      mothers had exercised during pregnancy significantly less than NBW mothers. When
      compared with NBW mothers before pregnancy, VLBW mothers had been just as likely
      not to exercise as NBW mothers (odds ratio (OR) = 0.88, 95% confidence interval
      (CI) 0.69-1.12). During the first, second, and third trimesters, the odds ratios
      decreased to 0.70 (95% CI 0.53-0.92), 0.54 (95% CI 0.40-0.74), and 0.33 (95% CI
      0.20-0.53), respectively. The VLBW mothers also were less likely to exercise
      during the third trimester than MLBW mothers (OR = 0.34, 95% CI 0.21-0.54) or
      mothers with fetal deaths (OR = 0.36, 95% CI 0.19-0.67). During the 3 months
      after pregnancy, none of the exercise odds ratios were statistically significant
      between groups. No significantly increased risks were found between employment
      during pregnancy or other daily activities and adverse pregnancy outcome. The
      study supports the recently relaxed guidelines of exercise during pregnancy.

PMID- 8561155
TI  - Smoking, drinking, and thinking. The Zutphen Elderly Study.
AB  - The authors examine the cross-sectional and longitudinal relation of smoking
      habits and current alcohol intake to cognitive status and decline over a 3-year
      period as well as the extent to which these relations are modified by the
      presence of clinical conditions indicating atherosclerosis (cardiovascular
      disease (CVD)/diabetes). Data are from the cohort of men followed in the
      longitudinal Zutphen Elderly Study in 1990 (n = 489) and 1993 (n = 333).
      Cognitive function was measured in 1990 and 1993 with the 30-point Mini-Mental
      State Examination (MMSE). After adjustment for age, education, and alcohol
      intake, current smokers made 20% more errors on the MMSE than never smokers in
      the cross-sectional analyses. Cognitive decline was greatest in those with
      CVD/diabetes who currently smoked and never smoked (-1.9 and -1.3 points,
      respectively). After adjustment for age, education, and smoking status, men with
      CVD/diabetes and low-to-moderate alcohol intake had a significantly lower risk
      for poor cognitive function (MMSE < or = 25) than abstainers (odds ratios of 0.3
      for less than one drink and 0.2 for one to two drinks per day). Alcohol intake
      was not associated with cognitive decline. These findings do not support the
      hypothesis of a protective effect of smoking on cognitive function; they suggest
      that smoking may be harmful among those with CVD/diabetes. Alcohol may result in
      an acute beneficial effect on cognitive function among those with CVD/diabetes.
      However, selection bias and unmeasured confounding should be of concern when
      evaluating these results.

PMID- 8561156
TI  - How useful is body mass index for comparison of body fatness across age, sex, and
      ethnic groups?
AB  - This study tested the hypothesis that body mass index (BMI) is representative of
      body fatness independent of age, sex, and ethnicity. Between 1986 and 1992, the
      authors studied a total of 202 black and 504 white men and women who resided in
      or near New York City, were ages 20-94 years, and had BMIs of 18-35 kg/m2. Total
      body fat, expressed as a percentage of body weight (BF%), was assessed using a
      four-compartment body composition model that does not rely on assumptions known
      to be age, sex, or ethnicity dependent. Statistically significant age
      dependencies were observed in the BF%-BMI relations in all four sex and ethnic
      groups (p values < 0.05-0.001) with older persons showing a higher BF% compared
      with younger persons with comparable BMIs. Statistically significant sex effects
      were also observed in BF%-BMI relations within each ethnic group (p values <
      0.001) after controlling first for age. For an equivalent BMI, women have
      significantly greater amounts of total body fat than do men throughout the entire
      adult life span. Ethnicity did not significantly influence the BF%-BMI relation
      after controlling first for age and sex even though both black women and men had
      longer appendicular bone lengths relative to stature (p values < 0.001 and 0.02,
      respectively) compared with white women and men. Body mass index alone accounted
      for 25% of between-individual differences in body fat percentage for the 706
      total subjects; adding age and sex as independent variables to the regression
      model increased the variance (r2) to 67%. These results suggest that BMI is age
      and sex dependent when used as an indicator of body fatness, but that it is
      ethnicity independent in black and white adults.

PMID- 8561157
TI  - Prospective study of beverage use and the risk of kidney stones.
AB  - Patients with kidney stones are routinely advised to increase their fluid intake
      to decrease the risk of stone recurrence. However, there has been no detailed
      examination to determine whether the effect on recurrence varies by the type of
      beverage consumed. The authors conducted a prospective study of the relation
      between the intake of 21 different beverages and the risk of symptomatic kidney
      stones in a cohort of 45,289 men, 40-75 years of age, who had no history of
      kidney stones. Beverage use and other dietary information was measured by means
      of a semiquantitative food frequency questionnaire in 1986. During 6 years of
      follow-up (242,100 person-years), 753 incident cases of kidney stones were
      documented. After adjusting simultaneously for age, dietary intake of calcium,
      animal protein and potassium, thiazide use, geographic region, profession, and
      total fluid intake, consumption of specific beverages significantly added to the
      prediction of kidney stone risk (p < 0.001). After mutually adjusting for the
      intake of other beverages, the risk of stone formation decreased by the following
      amount for each 240-ml (8-oz) serving consumed daily: caffeinated coffee, 10%
      (95% confidence interval 4-15%); decaffeinated coffee, 10% (3-16%); tea, 14% (5
      22%); beer, 21% (12-30%); and wine, 39% (10-58%). For each 240-ml serving
      consumed daily, the risk of stone formation increased by 35% (4-75%) for apple
      juice and 37% (1-85%) for grapefruit juice. The authors conclude that beverage
      type may have an effect on stone formation that involves more than additional
      fluid intake alone.

PMID- 8561158
TI  - Constitutional factors and sun exposure in relation to nevi: a population-based
      cross-sectional study.
AB  - A survey of benign melanocytic nevi (moles), suspected precursors or markers for
      melanoma, was conducted in Washington State among 717 randomly selected 18- to 50
      year-old white adults who participated in a telephone interview in 1990-1991.
      Participants were questioned about constitutional factors, time spent in the sun,
      and severe sunburns over three time periods and were asked to count the raised
      nevi on both their arms. Logistic regression was used to examine the risk for 2+
      nevi compared with none. An odds ratio (OR) of 2.0 (95% confidence interval (CI)
      1.3-3.1) was seen for current freckling. Skin color, tendency to burn, and
      inability to tan were important risk factors but were not independent of each
      other. Individuals with a history of severe sunburns had an increased risk of
      nevi: OR = 1.9 (95% CI 0.9-3.9) for 3+ severe sunburns compared with none in the
      last 5 years; OR = 2.0 (95% CI 1.2-3.1) for 4+ severe teenage sunburns; and OR =
      3.1 (95% CI 1.7-5.3) for 4+ severe childhood sunburns. Furthermore, childhood
      sunburns were related to nevi independently of sun sensitivity and teenage and
      recent sunburns: OR = 2.0 (95% CI 1.0-4.0) for 4+ severe sunburns. These data
      suggest that childhood sunburns are important in the etiology of nevi. This study
      supports prior studies of the relation between melanoma and early sun exposure.

PMID- 8561159
TI  - Prevalence of Helicobacter pylori infection in Korean children: inverse relation
      to socioeconomic status despite a uniformly high prevalence in adults.
AB  - The prevalence of Helicobacter pylori infection in US adults was shown to be
      inversely correlated with the socioeconomic status of the family during
      childhood, and it was suggested that this was additional evidence of transmission
      occurring in childhood. The present study of H. pylori infection was conducted in
      South Korea, which has emerged as a developed country in the last two decades.
      The authors attempted to determine whether there was a difference in prevalence
      of H. pylori infection in Korean children of different socioeconomic classes
      despite the high prevalence of infection in childbearing adults. The authors also
      attempted to identify the factors responsible for the different patterns of
      transmission by estimating the age-specific prevalence of H. pylori infection in
      413 healthy 1- to 75-year-old asymptomatic volunteers who resided in Seoul. H.
      pylori status was evaluated using an enzyme-linked immunosorbent assay for anti
      H. pylori immunoglobulin G. Demographic data were obtained from each individual,
      and socioeconomic class was assessed by the education level of the adults and of
      the children's parents as well as family income. H. pylori infection was present
      in 75% of adults and 22% of children, and its prevalence increased with age (p <
      0.001). In adults, the rate of infection was high and independent of
      socioeconomic class. In children, it was inversely related to the socioeconomic
      class of the child's family: 12% among upper socioeconomic class, 25% among the
      middle class, and 41% among the lowest class (p = 0.016). No associations were
      found between prevalence of H. pylori infection and any factor tested including
      sex, smoking, and alcohol consumption. In addition, type of housing, whether
      owned or rented, number of family members living in the same household, water
      source, and type of community in which a child grew up were not found to be risk
      factors influencing H. pylori infection prevalence. The prevalence of H. pylori
      infection in Korea appears to be changing with markedly lower prevalence in
      children of families of higher socioeconomic status. The factor(s) responsible
      for the break in the pattern of transmission in children of the higher
      socioeconomic class was not discovered. Future studies will concentrate on
      possible differences, eating practices, hygiene, and sanitary practices.

PMID- 8561160
TI  - Epidemiologic study of Vibrio cholerae O1 and O139 in Thailand: at the advancing
      edge of the eighth pandemic.
AB  - Vibrio cholerae O139 Bengal emerged on the Indian subcontinent in late 1992 and
      was first recognized in Thailand in 1993. To characterize the epidemiology of
      this disease, a hospital-based case-control study was conducted in Samutsakorn, a
      port city 30 km southwest of Bangkok. Between November 15, 1993, and June 3,
      1994, 366 patients were confirmed to have cholera by culture, including 165 (45%)
      with O139 Bengal, 191 (52%) with O1 Ogawa, and 10 (3%) with both serogroups.
      During the same time period the previous year, 319 culture-confirmed cholera
      cases occurred, all serogroup O1. Questionnaires were obtained from 105 patients
      with O139 Bengal and 103 with O1 infections; for each case patient, two
      asymptomatic age- and sex-matched control persons were selected. Of the patients
      with O139 Bengal infections, 93% were adults (> or = 15 years) compared with 92%
      of patients with O1 infections. Risk factors for cholera identified by case
      control comparisons were similar for the two serogroups and included consumption
      of untreated water, uncooked seafood, and food served at group gatherings. V.
      cholerae O139 Bengal has emerged in Thailand as a cause of endemic cholera, with
      epidemiologic features and incidence similar to those of the preexisting O1
      strain.

PMID- 8561161
TI  - Rural gonorrhea in the southeastern United States: a neglected epidemic?
AB  - Some rural counties in the southeastern United States are experiencing high rates
      of gonorrhea; however, existing knowledge of epidemiologic patterns of gonorrhea
      within communities is from urban areas. This paper describes the epidemiology of
      gonorrhea within a rural county of North Carolina and compares it with the
      patterns described for large cities. Data include gonorrhea reports from private
      physicians and the county health department from August 11, 1992, to August 10,
      1993, and ethnographic interviews. The rate among males (1,602 cases per 100,000
      person-years) was twice that among females. The risk of reinfection within 6
      months of an initial infection (12.9%) was high compared with risks in urban
      settings. Although case numbers did not cluster by geographical area as described
      for some cities, case rates did. Factors favoring transmission in rural
      communities include greater poverty and fewer health care resources than in urban
      settings, the exchange of sex for crack cocaine, and a lack of anonymity that may
      cause some people to avoid seeking treatment or acknowledging risky sexual
      behaviors in a clinical setting. Addressing high rural rates will entail
      improving access to care, taking extra measures to ensure confidentiality, and
      dispelling the myth that high rates are limited to cities.

PMID- 8561162
TI  - Temporal trends of initial CD4 cell counts following human immunodeficiency virus
      seroconversion in Italy, 1985-1992. The Human Immunodeficiency Virus Italian
      Seroconversion Study.
AB  - To determine whether initial CD4 cell counts after human immunodeficiency virus
      (HIV) seroconversion have decreased over calendar time among participants in the
      Italian Seroconversion Study, HIV seroconverters who between 1985 and 1992 had a
      documented negative serology followed by a positive serology within 12 months and
      a first CD4 cell measurement within 24 months of seroconversion (defined as
      midpoint of negative and positive HIV tests) were cross-tabulated by year of
      seroconversion. Linear regression methods were used to examine temporal trends in
      initial CD4 level after adjustment for age, lag time of seroconversion, lag time
      of CD4 cell measurement, risk group, and clinical center. Between 1985 and 1992,
      the overall median initial CD4 cell level after seroconversion was 660
      microliters with a median lag time of 212 days and 137 days for seroconversion
      and first CD4 cell measurement, respectively. In univariate and multivariate
      models, the CD4 cell count increases of 4.3 and 4.2 cells microliters/year,
      respectively, were not statistically significant. These data do not identify a
      trend of lower CD4 counts following HIV seroconversion in Italy and suggest
      indirectly that HIV has probably not become more virulent between 1985 and 1992.

PMID- 8561163
TI  - Use of proxies to measure health and functional status in epidemiologic studies
      of community-dwelling women aged 65 years and older.
AB  - Proxy and subject responses to survey questions about chronic conditions, health
      symptoms, and physical and instrumental functioning were compared to determine
      the extent of disagreement, the direction of nonrandom discrepancies (i.e.,
      bias), and how disagreement and bias vary by proxy and subject characteristics.
      Subjects included 538 community-dwelling women aged 65 years and older who
      participated in the third home interview of a health survey in Baltimore,
      Maryland, 1986, and a self-designated proxy for each. The authors observed kappa
      values of > 0.6 (i.e., substantial to almost perfect agreement) for five of nine
      chronic conditions, no health symptoms, six of seven physical tasks of daily
      living, and seven of seven instrumental tasks of daily living. With few
      exceptions, proxies were more likely than subjects to report the presence of a
      condition, symptom, or functional problem. Variations in agreement and bias were
      noted by subject and proxy characteristics, with different patterns observed for
      different measurement areas. When using proxy reports in place of self-reports,
      it is important to evaluate the impact that using proxies has on study results.

PMID- 8561164
TI  - Combined analysis of matched and unmatched case-control studies: comparison of
      risk estimates from different studies.
AB  - The authors propose a method to perform a combined analysis of matched and
      unmatched case-control studies that is based on an adaptation of logistic
      regression and can be performed using standard software. This methodology can be
      used to do pooled analyses of studies with different designs. Likelihood ratio
      tests can be performed to assess association, heterogeneity, or trend. The
      standard errors of the coefficients allow the derivation of a Wald test and the
      calculation of confidence intervals. Another application is to compare relative
      risk estimators for the same risk factors studied in different phases of a
      disease in an effort to explore factors that may be more important in one phase
      than in another. Interaction terms of risk factors with variables that code the
      different pooled studies can be used for this purpose. The advantage of using
      this method is that a formal statistical comparison can be performed in which the
      regression coefficients of the interaction terms estimate the relative
      differences in risk (odds ratio ratios) between the studies. This estimation can
      be adjusted for other confounder factors. Two examples of application using data
      from case-control studies on cervical cancer and colorectal cancer are presented
      to illustrate the use of this epidemiologic method.

PMID- 8561166
TI  - Invited commentary: snippets from the past: seventy years ago in the Journal.

PMID- 8561167
TI  - Disclosure of interest: response from our readers.

PMID- 8561165
TI  - Predicting the onset of Alzheimer's disease using Bayes' theorem.
AB  - Bayes' theorem describes the effect of new information (e.g., a test result) on
      the probability of an outcome (e.g., a disease). Likelihood ratios for separate
      tests can be combined to assess the joint effect of their results on disease
      probability. This approach has been used to develop a test package for
      Alzheimer's disease that consists of some simple cognitive tests (Paired
      Associate Learning Test, Trailmaking Test, and Raven's Progressive Matrices)
      combined with age and family history of dementia. A total of 1,454 subjects who
      had been recruited into the Medical Research Council Elderly Hypertension Trial
      between 1983 and 1985 completed cognitive tests at entry to the trial (when they
      were without signs of dementia) and 1 month later. Their dementia status was
      ascertained in 1990-1991. The test package identified 52% of Alzheimer's disease
      cases with a 9% false-positive rate or 90% of Alzheimer's disease cases with a
      29% false-positive rate. The author proposes the use of a similar test package in
      conjunction with a test for apolipoprotein E e4 status, which is a powerful risk
      factor for late-onset Alzheimer's disease, as a likelihood ratio approach to the
      prospective identification of Alzheimer's disease cases. This approach could be
      followed by ethically sound trials of new therapeutic agents for subjects who
      have a high probability of developing Alzheimer's disease.

PMID- 8561168
TI  - Effect of recall period on the reporting of occupational injuries among older
      workers in the Health and Retirement Study.
AB  - Studies of injury morbidity often rely on self-reported survey data. In designing
      these surveys, researchers must chose between a shorter recall period to minimize
      recall bias and a longer period to maximize the precision of rate estimates.
      Using data from the Health and Retirement Study, which employed a recall period
      of 1 year, we examined the effect of the recall period on rates of occupational
      injuries among older workers as well as upon rate ratios of these injuries for
      nine risk factors. We fit a stochastic model to the occupational injury rates as
      a function of time before the interview and used this model to estimate what the
      injury rates would have been had we used a 4-week recall period. The adjusted
      occupational injury rate of 5.9 injuries per 100 workers per year was 36% higher
      than the rate based on a 1-year recall period. Adjustment for recall period had
      much less effect on rate ratios, which typically varied by < 10%. Our work
      suggests that self-reported surveys with longer recall periods may be used to
      estimate occupational injury rates and also may be useful in studying the
      associations between occupational injuries and a variety of risk factors.

PMID- 8561169
TI  - Back pain among workers in the United States: national estimates and workers at
      high risk.
AB  - Back pain accounts for about one fourth of workers' compensation claims in the
      United States. The Occupational Health Supplement to the 1988 National Health
      Interview Survey provided an opportunity to assess the scope of this problem. The
      30,074 respondents who worked in the 12 months before the interview were defined
      as "workers", and those with back pain every day for a week or more during that
      period were defined as "cases." A weighting factor was applied to the answers to
      derive national estimates. In 1988, about 22.4 million back pain cases
      (prevalence 17.6%) were responsible for 149.1 million lost workdays; 65% of cases
      were attributable to occupational activities. For back pain attributed to
      activities at work, the risk was highest for construction laborers among males
      (prevalence 22.6%) and nursing aides among females (18.8%). Our analyses show
      that back pain is a major cause of morbidity and lost production for U.S. workers
      and identifies previously unrecognized high risk occupations, such as carpenters,
      automobile mechanics, maids, janitors, and hairdressers, for future research and
      prevention.

PMID- 8561170
TI  - Silica exposure and autoimmune diseases.
AB  - There have long been case reports linking silica exposure to a variety of
      autoimmune diseases (systemic sclerosis, rheumatoid arthritis, lupus, chronic
      renal disease). Evidence of this association in larger epidemiologic studies has
      been increasing in the last decade. We summarize this evidence here, and present
      some plausible mechanisms which have been discussed in the literature. The link
      between silica exposure and autoimmune disease may have been missed in cohort
      mortality studies because autoimmune diseases are rarely underlying causes of
      death. Similarly, case-control studies of autoimmune diseases have often failed
      to consider occupational exposure to silica. Further research is needed in
      occupationally exposed populations to verify this association. The link between
      respirable silica exposure and autoimmune disease may have some bearing on the
      possible association between silicone breast implants and autoimmune disease,
      although the nature of the silica involved is quite different in the two
      situations.

PMID- 8561171
TI  - Re: "Disclosure of interest: a time for clarity".

PMID- 8561173
TI  - Re: "Disclosure of interest: a time for clarity".

PMID- 8561172
TI  - Re: "Disclosure of interest: a time for clarity".

PMID- 8561174
TI  - The true conflict of interest.

PMID- 8561175
TI  - Re: "Disclosure of interest: a time for clarity".

PMID- 8561176
TI  - Re: "Disclosure of interest: a time for clarity".

PMID- 8561177
TI  - Disclosure of interest: additional thoughts.

PMID- 8561178
TI  - Re: "Disclosure of interest: a time for clarity".

PMID- 8561179
TI  - Legislating away reality.

PMID- 8561180
TI  - Toward a national standard of social health: the need for progress in social
      indicators.

PMID- 8561181
TI  - Episodically homeless women with serious mental illness: prevalence of physical
      and sexual assault.
AB  - Three aspects of physical and sexual assault in the histories of 99 episodically
      homeless, seriously mentally ill women were assessed: lifetime prevalence;
      severity, co-occurrence, and recency; and associations between levels of this
      victimization and specific characteristics of the women. Results indicate that
      the life-time risk for violent victimization was so high (97%) as to amount to
      normative experiences for this population.

PMID- 8561182
TI  - Building an empowerment policy paradigm: self-reported strengths of homeless
      mothers.
AB  - Self-reported strengths and goals of a sample of 64 mothers of young children
      residing in a temporary shelter for homeless families, were documented. The
      strengths most frequently reported included ability to take action, parental
      competence, and determination in the face of stress. Program and policy
      implications of these positive attributes of homeless mothers are discussed.

PMID- 8561183
TI  - Services for homeless pregnant women: lessons from the field.
AB  - Although a significant subset of homeless women are pregnant and at risk for
      adverse pregnancy outcomes, programmatic responses to their special needs are
      limited. Findings from the process evaluation of an innovative service
      demonstration program are explored, and recommendations for future service
      delivery efforts are offered.

PMID- 8561184
TI  - Implementation of the homeless families program: 1. Service models and
      preliminary outcomes.
AB  - The implementation and early outcomes of a large-scale, services-enriched housing
      program for homeless families are evaluated and examined across nine metropolitan
      sites. Differing models of case management and service access are described.
      Early reports on families' residential stability are high across all service
      models.

PMID- 8561185
TI  - Implementation of the homeless families program: 2. Characteristics, strengths,
      and needs of participant families.
AB  - The characteristics and needs of homeless families participating in a large-scale
      services-enriched housing program are examined. Although not a representative
      sample, participants constitute one of the largest subsets of homeless families
      in the literature. Moreover, the sample, which encompasses nine sites, is focused
      on families with multiple problems who have been recurrently homeless. Differing
      constellations of needs and implications for service delivery are explored.

PMID- 8561186
TI  - Trauma contagion in partners of survivors of childhood sexual abuse.
AB  - Partners of survivors of childhood sexual abuse may develop a "trauma contagion"
      marked by high levels of stress, doubts about to key personal values and
      assumptions about the world, and a tendency to be drawn into unconscious
      reenactments with the survivor of the abusive relationship. Various treatment
      interventions are discussed, especially conjoint work with the survivor.

PMID- 8561187
TI  - Adoption and mental health: a theoretical critique of the psychopathological
      model.
AB  - The extant research on adoption and mental health is reviewed, and an alternative
      interactionist perspective is offered that acknowledges the social embeddedness
      of experiences of adoption and infertility. While cultural factors enter into the
      etiology and medical definition of all mental health problems, the particular
      importance of considering cultural components when addressing the needs of
      individuals who hold a stigmatized social status is emphasized.

PMID- 8561189
TI  - Mediation of abusive childhood experiences: depression, dissociation, and
      negative life outcomes.
AB  - A study of 301 college undergraduates is employed to test a causal model which
      proposes that dissociation and depression act as mediator variables that develop
      from child abuse and lead to various negative outcomes. As predicted, child
      maltreatment was found to be related to negative life experiences, with
      depression and dissociation differentially mediating the various outcomes.

PMID- 8561188
TI  - Disclosure of donor insemination: parental attitudes.
AB  - Disclosures by parents with a child conceived by donor insemination were compared
      to those of parents with adopted children and parents with children conceived by
      in vitro fertilization. None of the donor-insemination parents had told their
      child. The factors found to create the greatest difficulties for disclosure were
      the father's infertility, the timing and method of telling, and the lack of
      genetic information for the child.

PMID- 8561190
TI  - The role of work identity in women's adjustment to divorce.
AB  - A study of the role of employment in the divorce adjustment of 40 women found
      work identity to be associated with higher self-esteem and lower distress. Four
      established components of work identity--meaningfulness, social
      interaction/support, productivity, and positive distraction--were assessed via
      qualitative analyses; links among various life contexts were examined; and
      postdivorce changes explored. Results support the role of work identity in
      divorced women's adjustment.

PMID- 8561191
TI  - Paternal caregiving and incest.

PMID- 8561192
TI  - Imaging for the clinical psychiatrist: facts, fantasies, and other musings.

PMID- 8561193
TI  - PET and the [15O]H2O technique, Part 3: Finding the location of significant
      regions.

PMID- 8561194
TI  - Initiation and adaptation: a paradigm for understanding psychotropic drug action.
AB  - OBJECTIVE: This article describes a paradigm--initiation and adaptation--within
      which to conceptualize the drug-induced neural plasticity that underlies the long
      term actions of psychotropic drugs in the brain. METHOD: Recent advances in
      neurobiology are reviewed. RESULTS: Recent developments in cellular and molecular
      neurobiology provide new conceptual and experimental tools for understanding the
      mechanisms by which psychotropic drugs produce long-lived alterations in brain
      function. Because of the availability of more robust animal models, the
      mechanisms by which drugs of abuse produce dependence are better understood than
      the mechanisms by which antidepressants, antipsychotics, and lithium produce
      their therapeutic effects. Nonetheless, the fundamental types of mechanisms
      appear to be similar: chronic drug administration drives the production of
      adaptations in postreceptor signaling pathways, including regulation of neural
      gene expression. Whether the results are deleterious or therapeutic depends on
      the precise neural systems targeted by a particular drug. CONCLUSIONS: Biological
      investigation in psychiatry has often focused too narrowly on synaptic
      pharmacology, especially on neurotransmitter turnover and neurotransmitter
      receptors. This review focuses on molecular and cellular changes in neural
      function that are produced as adaptations to chronic administration of addictive
      drugs such as psychostimulants and therapeutic drugs such as antidepressants. To
      understand normal brain function, psychopathology, and the actions of psychiatric
      treatments, and to exploit the eventual findings of psychiatric genetics,
      psychiatric research must now extend its efforts beyond the synapse, to an
      understanding of cellular and molecular neurobiology (in particular, postreceptor
      signal transduction) as well as to a better understanding of the architecture and
      function of neural systems. A paradigm is presented to help understand the long
      term effects of psychotropic drugs, including the latency in onset of their
      therapeutic actions.

PMID- 8561195
TI  - Women with bipolar illness: clinical and research issues.
AB  - OBJECTIVE: The purpose of this article is to review the literature concerning
      gender differences in the course of bipolar illness and discuss issues relevant
      to the treatment of women with the illness. METHOD: The literature concerning the
      following topics is reviewed: gender differences in the course of bipolar
      illness; effects of the female reproductive cycle on the course of bipolar
      illness; special considerations in the treatment of bipolar women (focusing on
      the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes); and
      hypotheses to explain the greater prevalence of rapid cycling among bipolar women
      than among bipolar men. RESULTS: Data clearly indicate that rapid cycling is more
      common among bipolar women. Data also suggest that bipolar women may have more
      depressive episodes (and fewer manic episodes) and may be more likely to suffer
      from mixed (as opposed to pure) mania than bipolar men. While it is clear that
      bipolar women are at high risk for postpartum episodes, the effects of other
      reproductive system events (i.e., puberty, menstrual cycle, pregnancy, menopause,
      use of oral contraceptives or hormone replacement therapy) on the course or
      treatment of bipolar illness have received little systematic study. It is unclear
      whether women are at higher risk than men for developing lithium-induced
      hypothyroidism. Higher rates of hypothyroidism, greater use of antidepressants,
      and gonadal steroid effects are possible explanations for the greater prevalence
      of rapid cycling among bipolar women. CONCLUSIONS: Gender differences in bipolar
      illness and the effects of the female reproductive system on the course and
      treatment of the illness deserve more study. The importance of a longitudinal
      approach to these questions is emphasized.

PMID- 8561196
TI  - Demonstration in vivo of reduced serotonin responsivity in the brain of untreated
      depressed patients.
AB  - OBJECTIVE: For over 25 years, it has been hypothesized that major depression is
      due to a deficiency of available serotonin or subsensitivity of key serotonin
      receptors in relevant brain regions. Direct evidence supporting this hypothesis
      has been lacking because of the difficulty in studying regional brain
      serotonergic function. The authors have developed a method for visualizing in
      vivo regional brain responses to serotonin release by comparing regional brain
      glucose metabolism after administration of the serotonin-releasing drug dl
      fenfluramine, relative to placebo. METHOD: Results with healthy subjects (N = 6)
      were compared to those obtained with drug-free inpatients with moderately severe
      major depression (N = 6). RESULTS: Healthy subjects had several areas of
      statistically significant increases in metabolism, mostly in the left prefrontal
      and temporoparietal cortex, and areas of decreased metabolism, such as in the
      right prefrontal cortex. In contrast, the depressed patients had no areas of
      increase or decrease in metabolism, differing significantly from healthy
      subjects. Results with patients resembled those with healthy subjects (N = 10)
      who were scanned twice without active drug on either occasion. CONCLUSIONS: This
      study provides the first direct visualization of blunted regional brain responses
      to serotonin release in the brain of patients with major depression, a finding
      that supports the hypothesis of impaired serotonergic transmission in depression.

PMID- 8561197
TI  - [123I]IBZM SPECT for imaging of striatal D2 dopamine receptors in 56
      schizophrenic patients taking various neuroleptics.
AB  - OBJECTIVE: The purpose of this study was to compare the binding of various
      typical and atypical neuroleptics to striatal D2 dopamine receptors in
      schizophrenic patients. METHOD: Fifty-six inpatients with schizophrenia,
      including 14 with schizoaffective disorder and one with schizophreniform
      disorder, were evaluated. Fourteen patients were neuroleptic free. Single photon
      emission computed tomography (SPECT) was performed 90 minutes after intravenous
      injection of [123I]benzamide ([123I]IBZM). Subsequent semiquantitative analysis
      of D2 receptor binding was done with the use of the basal ganglia
      (striatum)/frontal cortex (BG/FC) ratio of activity. Clinical symptoms were rated
      with the Positive and Negative Syndrome Scale and the Hamilton Depression Rating
      Scale. RESULTS: The BG/FC ratios in patients taking typical neuroleptics were
      significantly lower than those in the neuroleptic-free subjects but not lower
      than those in the patients taking atypical neuroleptics (clozapine, remoxipride).
      For atypical antipsychotics, a dose-dependent relationship with striatal D2
      receptor binding could not be demonstrated. BG/FC ratios were not significantly
      correlated with clinical symptoms or with duration of illness. CONCLUSIONS: The
      results indicate that [123I]IBZM SPECT is useful for semiquantitative imaging of
      striatal D2 dopamine receptors and for estimating their blockade by neuroleptics.
      Thus, it may improve drug monitoring in psychiatric patients. Furthermore, the
      findings suggest a complex relationship between the antipsychotic effect of
      atypical neuroleptics and D2 receptor blockade.

PMID- 8561199
TI  - Functional magnetic resonance imaging of schizophrenic patients and comparison
      subjects during word production.
AB  - OBJECTIVE: This study was undertaken to test the feasibility of using functional
      magnetic resonance imaging (MRI) to examine changes in cortical activation in
      response to verbal tasks in two brain regions. METHOD: Twelve schizophrenic
      patients and 11 comparison subjects underwent functional MRI of the frontal and
      temporal lobes. Stimulus sequences were divided into five 30-second segments by
      using a task-activation paradigm that alternated between resting and stimulated
      states. Functional images were collected every 30 seconds by using a gradient
      echo pulse sequence. RESULTS: Schizophrenic subjects demonstrated significantly
      less left frontal activation and greater left temporal activation than comparison
      subjects during a word fluency task. CONCLUSIONS: These preliminary data suggest
      that functional MRI has the sensitivity to detect differences in activation
      between comparison subjects and schizophrenic patients during higher cortical
      functions. These findings are in agreement with PET studies that reported reduced
      left frontal activation during challenge paradigms for the schizophrenic
      patients.

PMID- 8561198
TI  - PET and MRI of the thalamus in never-medicated patients with schizophrenia.
AB  - OBJECTIVE: This study reports the first paired measurements of glucose metabolism
      and size of thalamic regions in never-medicated schizophrenic patients using
      coregistered magnetic resonance imaging (MRI) templates. METHOD: Positron
      emission tomography with [18F]fluorodeoxyglucose and matching MRI scans were
      obtained in 20 never-medicated patients with schizophrenia and 15 normal
      volunteers. Methods for thalamic edge finding, statistical testing of shape
      differences with chi-square maps, and MRI localization of major thalamic
      subregions were developed. RESULTS: Patients with schizophrenia showed a
      diminished metabolic rate in the right thalamus, with a loss of the normal
      pattern of right greater than left asymmetry. Division into anterior/posterior
      segments revealed that the left anterior and right posterior showed the decrease.
      Differences were greater for metabolism in the weighted thalamic area (ratexarea)
      than for rate per unit area, a finding consistent with reported greater decreases
      in total neuron number than of neuron density in the thalami of schizophrenic
      patients. The area of the thalamus was smaller in the patients than in the
      volunteers, and this difference was greatest in the left anterior region.
      CONCLUSIONS: The reduced thalamic activity observed in this study lends further
      support to the concept of deficits in sensory filtering in schizophrenia.

PMID- 8561200
TI  - Cerebral blood flow changes in limbic regions induced by unsolvable anagram
      tasks.
AB  - OBJECTIVE: The study addressed the question of whether unsolvable as opposed to
      solvable cognitive problems activate discrete neuronal systems in the human
      brain. METHOD: Twelve healthy humans tried to solve unsolvable anagrams. Solvable
      anagrams and a resting baseline after each anagram task served as control
      conditions in a within-subject design. Activation was measured with the
      equilibrium infusion method by using 15O-labeled water and positron emission
      tomography, with absolute quantitation of anatomically defined regional cerebral
      blood flow (CBF). RESULTS: Compared to rest, both anagram tasks increased
      activity in frontal and temporal regions. The soluble task condition increased
      hippocampal activation and decreased mammillary bodies activity, while unsolvable
      anagrams were associated with increased CBF to the mamillary bodies and amygdala
      and decreased hippocampal activity. CONCLUSIONS: A limbic network integrating
      negative emotion and cognition seems reflected in reciprocal diencephalic and
      limbic activation with solvable and unsolvable anagrams. Since unsolvable
      anagrams have been used to induce learned helplessness in humans, this finding
      may provide an initial step toward clarifying its neural substrate.

PMID- 8561201
TI  - Functioning and well-being of patients with panic disorder.
AB  - OBJECTIVE: The authors compared the health-related quality of life of patients
      with panic disorder to that of patients with other major chronic medical and
      psychiatric conditions. METHOD: The physical and mental health of a group of 433
      patients with current panic disorder and 9,839 outpatients with psychiatric or
      medical disorders were assessed with the 20- and 36-item short-form surveys of
      the Medical Outcomes Study. After controlling for other disease conditions,
      demographics, and study site, the authors used multiple regression methods to
      estimate health-related quality of life levels for panic disorder patients and
      patients with hypertension, diabetes, heart disease, arthritis, chronic lung
      problems, and major depression. RESULTS: Patients with panic disorder had levels
      of mental health and role functioning that were substantially lower than those of
      patients with other major chronic medical illnesses but were higher than or
      comparable to those of patients with depression. However, their physical
      functioning levels and perceptions of current health were more like those of
      patients with hypertension and were similar to general population norms.
      CONCLUSIONS: Panic disorder is a serious societal health problem with large
      consequences, and it affects primarily psychological and role domains.

PMID- 8561202
TI  - Predictors of PTSD in injured trauma survivors: a prospective study.
AB  - OBJECTIVE: The aim of this study was to prospectively examine the relationship
      between immediate and short-term responses to a trauma and the subsequent
      development of posttraumatic stress disorder (PTSD). METHOD: All patients
      consecutively admitted to a general hospital were screened for the presence of
      physical injury due to a traumatic event. Fifty-one eligible subjects were
      assessed 1 week and 6 months after the trauma. The initial assessment included
      measures of event severity, peritraumatic dissociation, and symptoms of
      intrusion, avoidance, depression, and anxiety. The follow-up assessments added
      the PTSD module of the Structured Clinical Interview for DSM-III-R--Non-Patient
      Version and the civilian trauma version of the Mississippi Scale for Combat
      Related Posttraumatic Stress Disorder. RESULTS: Thirteen subjects (25.5%) met
      PTSD diagnostic criteria at follow-up. Subjects who developed PTSD had higher
      levels of peritraumatic dissociation and more severe depression, anxiety, and
      intrusive symptoms at the 1-week assessment. Peritraumatic dissociation predicted
      a diagnosis of PTSD after 6 months over and above the contribution of other
      variables and explained 29.4% of the variance of PTSD symptom intensity. Initial
      scores on the Impact of Event Scale predicted PTSD status with 92.3% sensitivity
      and 34.2% specificity. Symptoms of avoidance that were initially very mild
      intensified in the subjects who developed PTSD. CONCLUSIONS: Peritraumatic
      dissociation is strongly associated with the later development of PTSD. Early
      dissociation and PTSD symptoms can help the clinician identify subjects at higher
      risk for developing PTSD.

PMID- 8561203
TI  - Controlled prospective study on the mental health of women following pregnancy
      loss.
AB  - OBJECTIVE: This study investigated the hypothesis that following a pregnancy
      loss, women have more mental health complaints than women who give birth to a
      living baby. METHOD: Mental health was assessed for 2,140 women during their
      first trimester of pregnancy through use of the Dutch version of the SCL-90. A
      total of 227 women who had lost their babies and 213 women who gave birth to a
      living baby were followed over a period of 18 months, during which their mental
      health was reassessed four times. RESULTS: When mental health complaints at the
      beginning of pregnancy and reproductive loss history were taken into account,
      data analysis revealed that up to 6 months after their pregnancy loss, women
      showed greater depression, anxiety, and somatization than women who gave birth to
      living babies. Over time the mental health of women who had experienced a loss
      was found to improve and at 1 year was comparable to that of women who gave birth
      to living babies and to that of women in general. CONCLUSIONS: The majority of
      women are able to recover from pregnancy loss without psychiatric treatment in
      about 1 year. A pregnancy loss is nevertheless a stressful life event that can
      give rise to a marked deterioration in a woman's mental health, particularly in
      the first 6 months following loss.

PMID- 8561204
TI  - A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the
      treatment of delirium in hospitalized AIDS patients.
AB  - OBJECTIVE: The purpose of this study was to examine the efficacy and side effects
      of haloperidol, chlorpromazine, and lorazepam for the treatment of the symptoms
      of delirium in adult AIDS patients in a randomized, double-blind, comparison
      trial. METHOD: Nondelirious, medically hospitalized AIDS patients (N = 244)
      consented to participate in the study and were monitored prospectively for the
      development of delirium. Patients entered the treatment phase of the study if
      they met DSM-III-R criteria for delirium and scored 13 or greater on the Delirium
      Rating Scale. Thirty patients were randomly assigned to treatment with
      haloperidol (N = 11), chlorpromazine (N = 13), or lorazepam (N = 6). Efficacy and
      side effects associated with the treatment were measured with repeated
      assessments using the Delirium Rating Scale, the Mini-Mental State, and the
      Extrapyramidal Symptom Rating Scale. RESULTS: Treatment with either haloperidol
      or chlorpromazine in relatively low doses resulted in significant improvement in
      the symptoms of delirium as measured by the Delirium Rating Scale. No improvement
      in the symptoms of delirium was found in the lorazepam group. Cognitive function,
      as measured by the Mini-Mental State, improved significantly from baseline to day
      2 for patients receiving chlorpromazine. Treatment with haloperidol or
      chlorpromazine was associated with an extremely low prevalence of extrapyramidal
      side effects. All patients receiving lorazepam, however, developed treatment
      limiting adverse effects. Although only a small number of patients had been
      treated with lorazepam, the authors became sufficiently concerned with the
      adverse effects to terminate that arm of the protocol early. CONCLUSIONS:
      Symptoms of delirium in medically hospitalized AIDS patients may be treated
      efficaciously with few side effects by using low-dose neuroleptics (haloperidol
      or chlorpromazine). Lorazepam alone appears to be ineffective and associated with
      treatment-limiting adverse effects.

PMID- 8561205
TI  - Interest in physician-assisted suicide among ambulatory HIV-infected patients.
AB  - OBJECTIVE: This study surveyed HIV-infected patients' attitudes toward physician
      assisted suicide and examined the relationship between interest in physician
      assisted suicide and physical and psychosocial variables. METHOD: Three hundred
      seventy-eight ambulatory HIV-infected patients, 90% of whom met the criteria of
      the Centers for Disease Control for AIDS, were recruited from several sites in
      New York City. Self-report measures were used to assess pain, physical symptoms,
      psychological distress, depression, and social supports. Attitudes toward, and
      interest in, physician-assisted suicide were assessed through responses to a
      questionnaire. RESULTS: Sixty-three percent of the patients supported policies
      favoring physician-assisted suicide, and 55% acknowledged considering physician
      assisted suicide as an option for themselves. The strongest predictors of
      interest in physician-assisted suicide were high scores on measures of
      psychological distress (depression, hopelessness, suicidal ideation, overall
      psychological distress) and experience with terminal illness in a family member
      or friend. Other strong predictors were Caucasian race, infrequent or no
      attendance at religious services, and perceived low level of social supports.
      Interest in physician-assisted suicide was not related to severity of pain, pain
      related functional impairment, physical symptoms, or extent of HIV disease.
      CONCLUSIONS: HIV-infected patients supported policies favoring physician-assisted
      suicide at rates comparable to those in the general public. Patients' interest in
      physician-assisted suicide appeared to be more a function of psychological
      distress and social factors than physical factors. These findings highlight the
      importance of psychiatric and psychosocial assessment and intervention in the
      care of patients who express interest in or request physician-assisted suicide.

PMID- 8561206
TI  - Relationship of aggressive behavior to other neuropsychiatric symptoms in
      patients with Alzheimer's disease.
AB  - OBJECTIVE: This study explored the relationship between aggressive behavior and
      other neuropsychiatric symptoms in patients with Alzheimer's disease. METHOD:
      Consecutively assessed outpatients with probable or possible Alzheimer's disease
      (N = 75) were assessed with the Behavioral Pathology in Alzheimer's Disease
      Rating Scale and the Hamilton Depression Rating Scale. RESULTS: Twenty-five
      patients (33%) had verbal outbursts and 13 patients (17%) engaged in physical
      aggression in the month prior to assessment. Aggressive patients and
      nonaggressive patients did not differ regarding age, education, gender, level of
      depression, or severity of dementia. In the entire group, dysphoria was found in
      33%, delusional ideation in 39%, and hallucinations in 16%. Aggressive behavior
      was more frequent among patients with hallucinations than among those without.
      Scores on hallucinations and activity disturbance predicted 12% of the variance
      in total aggressive behavior. When data from patients taking psychotropic
      medication were excluded from the analysis, hallucination and delusion scores
      predicted 22% of the variance in the aggression score. Physical aggression was
      associated with activity disturbance and hallucinations, and verbal aggression
      was associated with delusional ideation. No other clinical correlates of
      aggression were identified. CONCLUSIONS: Aggressive behavior is a frequent
      behavioral symptom in Alzheimer's disease. About one-fourth of the variance in
      aggression could be attributed to psychosis.

PMID- 8561207
TI  - Demographics, family history, premorbid functioning, developmental
      characteristics, and course of patients with deteriorated affective disorder.
AB  - OBJECTIVE: This exploratory study examined the characteristics of a group of
      unusual and previously undescribed patients with major affective disorder who not
      only had been continuously symptomatic for prolonged periods of time but were
      also so functionally impaired that they required years of continuous care in
      psychiatric facilities or by family members. METHOD: Twenty-seven inpatients with
      major mood disorders and 29 inpatients with schizophrenia were recruited from a
      large state hospital; 27 outpatients with major mood disorders were recruited
      from an affiliated outpatient facility. The research battery included the
      Structured Clinical Interview for DSM-III-R--Patient Version, the Premorbid
      Adjustment Scale, and a semistructured interview designed to assess demographic,
      family history, developmental, and course information. RESULTS: Inpatients with
      deteriorated affective disorder differed from outpatients with nondeteriorated
      affective disorder along several important dimensions, including family history
      of mental illness, birth-related problems, physical disorders in infancy,
      premorbid functioning, presence of mixed episodes and rapid cycling, and
      medication non-compliance between hospitalizations. Inpatients with deteriorated
      affective disorder differed from inpatients with schizophrenia on the Premorbid
      Adjustment Scale. Patients with bipolar affective disorder differed from those
      with unipolar disorder on many of the variables associated with deterioration of
      functioning. CONCLUSIONS: Birth-related problems, physical disorders in infancy,
      and poor premorbid adjustment in childhood and adolescence appear to play an
      important role in deterioration of functioning among patients with unipolar
      depression. Disruption in treatment because of medication noncompliance and the
      appearance of mixed episodes and rapid cycling are associated with functional
      decline in bipolar affective disorder. Several characteristics previously
      considered specific to deterioration of functioning in schizophrenia, such as a
      high rate of birth complications and poor premorbid adjustment, appear to be
      associated with functional deterioration among patients with major depression as
      well.

PMID- 8561208
TI  - Managed care constraints on psychiatrists' hospital practices: bargaining power
      and professional autonomy.
AB  - OBJECTIVE: The increasing involvement of insurers and hospitals in monitoring
      patient care is encroaching on the psychiatrist's autonomy in making clinical
      decisions. This study examined the prevalence of constraints on psychiatric
      inpatient practices, as well as how characteristics of psychiatrists affect the
      type and the degree of these external pressures. METHOD: About 2,500
      psychiatrists with active hospital affiliations were surveyed by mail, as a
      subset of APA's 1988 national survey of psychiatrists. They were questioned about
      whether the hospital or insurers had pressured them to change their inpatient
      practices or had attempted to discourage admission of certain types of patients.
      Characteristics of the psychiatrists' background, available from the main survey,
      were used as independent variables in a set of regression models, with frequency
      of different constraints as the dependent variables. RESULTS: More than three
      quarters of those surveyed reported pressure from insurers for early discharge;
      nearly two-thirds said hospitals limited length of stay; and about half had been
      discouraged from admitting severely ill patients, the uninsured, or Medicaid
      recipients. Characteristics of psychiatrists, such as length of time in practice,
      income, sex, and medical school education outside the United States, were
      associated with the prevalence of external pressures. CONCLUSIONS: Constraints on
      psychiatrists' practices are widespread. Their ability to resist pressures
      depends on their bargaining power, which seems to be lowest for those who have
      relatively little experience, who are female, or who have gone to medical school
      outside the United States. Psychiatrists appear to be willing to trade off more
      constraints for higher incomes. Severely ill patients and those with little or no
      insurance are more likely than others to be affected by these limits on
      psychiatrists' autonomy.

PMID- 8561209
TI  - Acute manic episodes in pregnancy.
AB  - A 33-year-old pregnant woman at 26 weeks gestation, who had a history of bipolar
      mood disorder, type I, was admitted to the hospital for hypomania and poorly
      controlled diabetes mellitus. The patient had had her first episode of affective
      illness at age 28, after the birth of her second child. After an initial
      postpartum depression, she had cycled into a manic state. She had subsequently
      been hospitalized seven times for acute mania. A combination of valproate and
      chlorpromazine had proven effective in managing most of her manic episodes, while
      her two most severe episodes had been successfully managed with bilateral ECT.

PMID- 8561210
TI  - Qualitative changes in hallucinations.
AB  - OBJECTIVE: This study examined which characteristics of hallucinations are most
      likely to change after inpatient treatment. METHOD: Fifty hallucinating
      psychiatric inpatients were given semistructured interviews shortly after
      admission and again shortly before discharge to elicit detailed descriptions of
      12 characteristics of hallucinations. RESULTS: Twenty-eight (56%) of the 50
      patients continued to report hallucinations after inpatient treatment.
      Posttreatment hallucinations differed significantly from pretreatment
      hallucinations in that they were less frequent, less intense, and less likely to
      prompt overt behavioral responses. Other characteristics of hallucinations
      remained relatively stable. CONCLUSIONS: Even when treatment does not eliminate
      hallucinations, it may alter them significantly. Outcome criteria that consider
      only the presence or absence of hallucinations may miss important changes in the
      nature of the symptom. This demonstrates that there is no simple "on-off switch"
      for hallucinations and supports multifactorial theories of the etiology of
      hallucinations.

PMID- 8561211
TI  - No evidence for allelic association between schizophrenia and a polymorphism
      determining high or low catechol O-methyltransferase activity.
AB  - OBJECTIVE: Catechol O-methyltransferase (COMT) inactivates catecholamines by
      methylating their m-hydroxy group. Some previous studies using biochemical
      methods have found higher levels of COMT activity in schizophrenic patients.
      Recently, the genetic polymorphism that underlies variation in COMT activity,
      which results in the creation of a NlaIII restriction site in the low-activity
      allele, has been elucidated. METHOD: This study investigated this polymorphism in
      78 unrelated schizophrenic patients and 78 comparison subjects matched for age
      and ethnicity. High-molecular-weight DNA was isolated from lymphocytes with
      routine procedures, and each individual was typed for high and low COMT activity.
      RESULTS: The frequency of the NlaIII polymorphism was 0.51 in the schizophrenic
      patients and 0.53 in the comparison subjects, and no significant allelic or
      genotypic associations were observed. CONCLUSIONS: There was no evidence for
      variation in COMT activity between a group of schizophrenic patients and matched
      comparison subjects.

PMID- 8561212
TI  - Further tests for linkage of bipolar affective disorder to the tyrosine
      hydroxylase gene locus on chromosome 11p15 in a new series of multiplex British
      affective disorder pedigrees.
AB  - OBJECTIVE: This study was undertaken to confirm or refute previous reports that
      link bipolar affective disorder to polymorphic DNA markers at or near the gene
      for tyrosine hydroxylase. METHOD: A previous linkage analysis, which used a
      tetranucleotide repeat polymorphism at the tyrosine hydroxylase locus, of six
      Icelandic families was extended to include a new series of 17 multiply affected
      British families. RESULTS: Overall lod scores under the assumption of locus
      heterogeneity were between 1.20 and 1.40 at zero recombination with tyrosine
      hydroxylase, and these scores persisted across three affective disorder models.
      CONCLUSIONS: These results provide some support for linking affective disorder to
      this genetic region and suggest that additional linkage and association studies
      should be conducted to determine whether tyrosine hydroxylase or a nearby locus
      contributes to susceptibility to bipolar affective disorder in some families.

PMID- 8561213
TI  - Childhood physical and sexual abuse in patients with anxiety disorders and in a
      community sample.
AB  - OBJECTIVE: The authors investigated whether histories of childhood physical or
      sexual abuse were reported more frequently in a clinical sample of patients with
      anxiety disorders than in a matched community comparison sample. METHOD: A
      standardized interview with an extensive series of trauma probes was administered
      to 125 patients with DSM-IV anxiety disorders (panic disorder, social phobia, or
      obsessive-compulsive disorder) and to 125 age- and gender-matched subjects drawn
      from a random community sample. RESULTS: Childhood physical abuse was higher
      among both men (15.5%) and women (33.3%) with anxiety disorders than among
      comparison subjects (8.1%). Childhood sexual abuse was higher among women with
      anxiety disorders (45.1%) than among comparison women (15.4%) and was higher
      among women with panic disorder (60.0%) than among women with other anxiety
      disorders (30.8%). CONCLUSIONS: These findings confirm the association between
      anxiety disorders and reported childhood physical and sexual abuse and extend
      earlier findings by pointing to a particular association between sexual abuse and
      panic disorder in women.

PMID- 8561214
TI  - Social phobia in adults with stuttering.
AB  - OBJECTIVE: The authors evaluated features of social anxiety in a group of adult
      stutterers to explore the soundness of the DSM-IV requirement that social phobia
      not be diagnosed in patients who stutter if their phobia relates to their
      stuttering. METHOD: They conducted diagnostic interviews and verbal fluency
      assessments with 16 consecutive adults seeking speech therapy for stuttering.
      Patients also completed scales measuring social phobia symptoms and associated
      disability. RESULTS: When DSM-IV criteria were modified to permit a diagnosis of
      social phobia if phobic symptoms were clearly excessive in relation to the
      severity of stuttering, seven of the 16 patients were given a diagnosis of social
      phobia. All seven identified social anxiety as an important source of role
      impairment. Three of the seven patients entered cognitive-behavioral group
      therapy and benefited from this intervention. CONCLUSIONS: Many adults seeking
      treatment for stuttering have salient difficulties with social anxiety that may
      prove amenable to cognitive-behavioral interventions. By precluding a diagnosis
      of social phobia in these patients, DSM-IV may hinder the identification of
      social anxiety as a source of disability and may limit access to treatment.

PMID- 8561215
TI  - Experience of a "slip" among alcoholics treated with naltrexone or placebo.
AB  - OBJECTIVE: This study tested the hypothesis that naltrexone reduces relapse rates
      among alcoholics by modifying the reinforcing effects of initial alcohol
      consumption and alcohol-induced craving. METHOD: Sixteen alcoholic patients
      treated with naltrexone and 27 treated with placebo who participated in a 12-week
      clinical trial reported retrospectively on their subjective responses to their
      first episode of a lapse into alcohol consumption and on their reasons for
      terminating the drinking episode. RESULTS: Compared to the subjects who received
      placebo, the subjects who received naltrexone reported lower levels of craving
      for alcohol and were more likely to give reasons for terminating drinking that
      were consistent with decreased incentive to drink. CONCLUSIONS: These findings
      support the hypothesis that a central effect of naltrexone is the modification of
      alcohol-induced craving.

PMID- 8561216
TI  - Disappearance of psychosis after buspirone treatment.

PMID- 8561217
TI  - Neuroleptic-induced bilateral temporomandibular joint dislocation.

PMID- 8561218
TI  - Treatment of chronic fatigue syndrome with venlafaxine.

PMID- 8561219
TI  - Influence of current events on psychopathology.

PMID- 8561220
TI  - Nortriptyline treatment of breast-feeding women.

PMID- 8561221
TI  - Hypokalemia in eating disorders.

PMID- 8561222
TI  - International medical graduates in psychiatric manpower calculations.

PMID- 8561223
TI  - Military position on homosexuality.

PMID- 8561224
TI  - Grief and object constancy.

PMID- 8561225
TI  - Anosognosia for depressive signs.

PMID- 8561226
TI  - Accidents and acts of God: a history of the terms.
AB  - Despite criticism from safety professionals, scientists continue to use the word
      accident, meaning an unexpected, unintended injury, or event. Some argue for its
      use based on tradition, but "traditional" arguments appear to be invalid given
      our examination of the history of the word and its companion phrase act of God in
      statistics, law, and religion. People who were interested in public health
      recognized in the 1600s that unintended injuries were neither random nor
      unexpected. Legal scholars in the 1800s saw the word was useless for technical
      purposes. The word does not appear in the Bible until the mid 1900s and then only
      in a para-phrased edition. Others have maintained that the meaning of accident is
      well understood, even though it has not been perfectly defined. We maintain that
      without a clear definition, people substitute an image, which may be distorted or
      damaging.

PMID- 8561227
TI  - What is the matter with the medical profession? 1912.

PMID- 8561228
TI  - Mercury use in espiritismo: a survey of botanicas.

PMID- 8561229
TI  - Blood lead levels, scientific misconduct, and the Needleman case. 1. A reply from
      the lead industry.

PMID- 8561230
TI  - Blood lead levels, scientific misconduct and the Needleman case. 2. The critics'
      arguments.

PMID- 8561231
TI  - Blood lead levels, scientific misconduct and the Needleman case. 3. A reply from
      Scarr and Ernhart.

PMID- 8561232
TI  - Is a rational, national drug policy possible?

PMID- 8561233
TI  - Preventing injuries from violence towards women.

PMID- 8561234
TI  - The high cost of injuries in the United States.

PMID- 8561235
TI  - Rape is a major public health issue.

PMID- 8561236
TI  - Smokers' knowledge and understanding of advertised tar numbers: health policy
      implications.
AB  - OBJECTIVES: This article examines health policy implications of providing smokers
      with numerical tar yield information in cigarette advertising. METHODS: Results
      of a national probability telephone survey regarding smokers' knowledge and
      understanding of numerical tar yields and deliveries are reported. RESULTS: Few
      smokers knew the tar level of their own cigarettes (the exception being smokers
      of 1- to 5-mg tar cigarettes), and a majority could not correctly judge the
      relative tar levels of cigarettes. Smokers were unsure whether switching to lower
      tar cigarettes would reduce their personal health risks. Many smokers relied on
      absolute numbers in making trade-offs between number of cigarettes smoked and
      their tar levels, thus confusion machine-rated tar-yields with actual amounts
      ingested. CONCLUSIONS: The wisdom of the present method of providing tar and
      nicotine numbers in ads and recommendations for modifying the test protocol are
      now under discussion. This research indicates that these tar numbers and their
      implications are poorly understood. The paper recommends revisions in tar ratings
      to make them more useful and a required statement on cigarette packages to more
      explicitly relate tar levels to major health risks.

PMID- 8561238
TI  - Reducing death on the road: the effects of minimum safety standards, publicized
      crash tests, seat belts, and alcohol.
AB  - OBJECTIVES: Two phases of attempts to improve passenger car crash worthiness have
      occurred: minimum safety standards and publicized crash tests. This study
      evaluated these attempts, as well as changes in seat belt and alcohol use, in
      terms of their effect on occupant death and fatal crash rates. METHODS: Data on
      passenger car occupant fatalities and total involvement in fatal crashes, for
      1975 through 1991, were obtained from the Fatal Accident Reporting System. Rates
      per mile were calculated through published sources on vehicle use by vehicle age.
      Regression estimates of effects of regulation, publicized crash tests, seat belt
      use and alcohol involvement were obtained. RESULTS: Substantial reductions in
      fatalities occurred in the vehicle model years from the late 1960s through most
      of the 1970s, when federal standards were applied. Some additional increments in
      reduced death rates, attributable to additional improved vehicle crashworthiness,
      occurred during the period of publicized crash tests. Increased seat belt use and
      reduced alcohol use also contributed significantly to reduced deaths.
      CONCLUSIONS: Minimum safety standards, crashworthiness improvements, seat belt
      use laws, and reduced alcohol use each contributed to a large reduction in
      passenger car occupant deaths.

PMID- 8561239
TI  - Violence and injury in marital arguments: risk patterns and gender differences.
AB  - OBJECTIVES: Community-based research on violence against women typically focuses
      on marital arguments rather than on resulting injuries. This study investigated
      patterns of victimization, violence perpetration, and injury in marital
      arguments. METHODS: Data from the National Survey on Families and Households and
      binomial and multinomial logit models were used to analyze characteristics of
      those who experienced physical violence, as well as to determine who was the
      perpetrator and who was the victim. RESULTS: Men and women reported similar
      behaviors during verbal arguments. Young persons, urban dwellers, the less
      educated, those with low incomes, and Blacks were more likely to report that
      there had been physical violence in their marriages in the past year. Ethnicity,
      income, education, and number and age of children at home were not associated
      consistently with injury of the wife, the husband, or both. CONCLUSIONS: Persons
      who report physical violence in their marriage are very similar to those who are
      at increased risk of interpersonal violence in general. The co-occurrence of
      street and other nonfamily violence with spousal violence may be a fruitful area
      for future research.

PMID- 8561237
TI  - Activity level and risk of overweight in male health professionals.
AB  - OBJECTIVES: This study undertook to examine relationships between nonsedentary
      activity level, time spent watching television (TV)/videocassette recorder (VCR),
      and risk of overweight among men. METHODS: Men participating in the Health
      Professionals Follow-Up Study were mailed surveys. Cross-sectional analyses
      examined the prevalence and odds of being overweight, prospective analyses
      determined cumulative incidence rates and relative risks of becoming overweight
      over 2 years of follow-up. RESULTS: Cross-sectionally, odds of being overweight
      were 50% (95% confidence interval [CI] = 45%; 55%) lower for men in the highest
      quintile of nonsedentary activity level when compared with men in the lowest
      quintile. Among men watching 41 or more hours of TV/VCR per week, the odds of
      being overweight were 406 (95% CI = 2.67, 6.17) times greater than those for men
      watching no more than 1 hour per week. Prospectively, higher levels is of
      nonsedentary activity and lower levels of TV/VCR viewing were independently
      associated with lower relative risks for becoming overweight between survey
      years. CONCLUSIONS: Both a lack of nonsedentary activity and time spent watching
      TV/VCR contribute to the development of overweight in men. Sedentary and
      nonsedentary activities represent separate domains, each with independent risks
      for overweight.

PMID- 8561240
TI  - Motorcycle helmet use and injury outcome and hospitalization costs from crashes
      in Washington State.
AB  - OBJECTIVES: The incidence, type, severity, and costs of crash-related injuries
      requiring hospitalization or resulting in death were compared for helmeted and
      unhelmeted motorcyclists. METHODS: This was a retrospective cohort study of
      injured motorcyclists in Washington State in 1989. Motorcycle crash data were
      linked to statewide hospitalization and death data. RESULTS: The 2090 crashes
      included in this study resulted in 409 hospitalizations (20%) and 59 fatalities
      (28%). Although unhelmeted motorcyclists were only slightly more likely to be
      hospitalized overall, they were more severely injured, nearly three times more
      likely to have been head injured, and nearly four times more likely to have been
      severely or critically head injured than helmeted riders. Unhelmeted riders were
      also more likely to be readmitted to a hospital for follow-up treatment and to
      die from their injuries. The average hospital stay for unhelmeted motorcyclists
      was longer, and cost more per case; the cost of hospitalization for unhelmeted
      motorcyclists was 60% more overall ($3.5 vs $2.2 million). CONCLUSIONS: Helmet
      use is strongly associated with reduced probability and severity of injury,
      reduced economic impact, and a reduction in motorcyclist deaths.

PMID- 8561241
TI  - The effects of a 4-year program promoting bicycle helmet use among children in
      Quebec.
AB  - OBJECTIVES: This study assessed the effectiveness of a 4-year program of bicycle
      helmet promotion that targeted elementary school children in one region of
      Quebec. The program revolved primarily around persuasive communication and
      community organization, combining standard educational activities and activities
      to facilitate helmet acquisition and use. METHODS: Helmet use was compared
      between more than 8000 young cyclists in municipalities exposed or not exposed to
      the program. Factors influencing helmet use were controlled through the use of
      multivariate analyses. RESULTS: Helmet use increased from 1.3% before program
      implementation to 33% in 1993. The program was clearly effective in most cycling
      circumstances and for various groups of children. However, the benefits of the
      program were unequally distributed; the program was one third as effective in
      poorer municipalities as in "average-rich" ones. CONCLUSIONS: This community
      based program that combined various types of activities appeared to be effective.
      New intervention models are needed to ensure an equitable distribution of
      benefits.

PMID- 8561242
TI  - Workers' compensation recipients with carpal tunnel syndrome: the validity of
      self-reported health measures.
AB  - OBJECTIVES: This study compared the reliability, validity, and responsiveness of
      self-reported measures of health related quality of life in recipients and non
      recipients of workers' compensation who have carpal tunnel syndrome. METHODS:
      Patients with carpal tunnel syndrome complete questionnaires at study enrollment
      and 6 months later scales measuring symptom severity functional status, and
      satisfaction were included. The scales internal consistency, validity, and
      responsiveness were assessed. RESULTS: The internal consistencies for each scale
      were high (Cronbach's alpha .88 to .96) and virtually identical in recipients and
      nonrecipients of workers' compensation. The correlations between self-reported
      and objectively measured grip strength were .32 in recipients and .30 in
      nonrecipients; these correlations were not influenced by whether workers'
      compensation recipients were out of work. Correlations between changes in scale
      scores and three indicators of perceived improvement were higher in recipients
      (.48 to .69) than in nonrecipients (.19 to .41) CONCLUSIONS: The reliability,
      validity, and responsiveness of these measures were comparable in nonrecipients
      and recipients of workers compensation, these data support the use of self-report
      measures in studies of workers.

PMID- 8561243
TI  - The effect of walking on lower body disability among older blacks and whites.
AB  - OBJECTIVES: This study investigated the association between regular physical
      activity and risk of or increase in lower body disability in older, community
      dwelling Blacks and Whites. METHODS: The present study used the 1984 to 1990
      Longitudinal Study on Aging, which included 413 Black and 3428 White self
      respondents 70 years of age or older. Discrete-time hazard models provided
      estimates of the effects of self-reported walking frequency, and regular exercise
      on lower, body disability among Black and White self-respondents. RESULTS: Whites
      who reported walking 4 to 7 days per week at baseline vs those who reported never
      walking 1 mile (1.6 km) or more experienced a one-third lower risk of increased
      disability. Blacks who reported walking 4 to 7 days per week experienced a two
      thirds lower risk. Walking 4 to 7 days per week reduced the risk of disability
      onset by 50% to 80% on all five disability items within the Black sample and by
      50% on two items within the White sample. CONCLUSIONS: Among older Blacks,
      walking 4 to 7 days per week had a greater protective effect against lower body
      decline than any of the other factors, including age and chronic conditions.

PMID- 8561244
TI  - The loss of independence in activities of daily living: the role of low normal
      cognitive function in elderly nuns.
AB  - OBJECTIVES: This study investigated the role of low normal cognitive function in
      the subsequent loss of independence in activities of daily living. METHODS: Of
      the 678 elderly nuns who-completed cognitive and physical function assessments in
      1992/93, 575 were reassessed in 1993/94. Mini-Mental State Examination scores
      were divided into three categories and related to loss of independence in six
      activities of daily living. RESULTS: Participants with low normal cognitive
      function at first assessment had twice the risk of losing independence in three
      activities of daily living by second assessment relative to those with high
      normal cognitive function. This relationship was largely due to a progression
      from low normal cognitive function at first assessment to impaired cognitive
      function at second assessment and was associated with an elevated risk of losing
      independence in the six activities. CONCLUSIONS: Progression from low normal to
      impaired cognitive function was associated with loss of independence in
      activities of daily living. Thus low normal cognitive function could be viewed as
      an early warning of impending cognitive impairment and loss of physical function.

PMID- 8561245
TI  - Injuries among inner-city minority women: a population-based longitudinal study.
AB  - Active emergency department-based surveillance was conducted to determine the
      incidence of fatal and nonfatal injuries in an urban, female African American
      population from 1987 through 1990. Nearly 40% of the women studied sustained one
      or more injuries that required emergency care or resulted in death. By 1989,
      violence had surpassed falls as the leading cause of injuries, the rate increased
      by 55% over the study period. Injury rates were highest among young women for
      nearly every major cause of injury. The rate of death due to injuries was also
      highest among young women, for whom violence was the leading cause of death. In
      summary, injuries to women in this inner-city minority community were extremely
      common and increased significantly from 1987 to 1990. Injuries in young inner
      city minority women should be considered a priority health problem in the United
      States.

PMID- 8561247
TI  - Occupational injury mortality rates in the United States: changes from 1980 to
      1989.
AB  - Changes in occupational injury mortality rates over the 1980s were examined
      through analysis of the National Traumatic Occupational Fatalities surveillance
      system. The US occupational injury mortality rate decreased 37% over the decade,
      with decreases seen in nearly every demographic and employment sector. Greater
      declines were among men, Blacks, and younger workers, as well as among
      agricultural, trade, and service workers. Electrocutions, machine-related
      incidents, and homicides showed the greatest decreases. Changes in occupational
      mortality rates by demography, industry, and cause of death indicate the areas in
      which the most progress has been made and those that are prime targets for
      prevention efforts.

PMID- 8561246
TI  - Total hip arthroplasty: use and select complications in the US Medicare
      population.
AB  - Use and outcomes of primary total hip arthroplasty among US Medicare recipients
      more than 65 years of age were investigated by means of physician and hospital
      claims for a 5% random sample during 1986 through 1989. Cases involving hip
      fracture or evidence of existing orthopedic devices in the hip were omitted. Use
      rates were higher for women than for men and were substantially lower for Blacks
      than Whites. Major complications (death, further hip surgery, infection pulmonary
      embolism) were uncommon. These data document the frequent use of total hip
      arthroplasty, and confirm the rarity of serious adverse outcomes. Further studies
      should investigate the lower use of total hip arthroplasty among Blacks.

PMID- 8561248
TI  - A survey of injuries among Broadway performers.
AB  - To obtain more information about injuries of Broadway performers, 313 performers
      appearing in 23 Broadway companies were surveyed. The percentage of performers
      injured was 55.5%, with a mean of 1.08 injuries performer. Lower extremity
      injuries were the most common. Sixty-two percent of performers believed that
      their injuries were preventable. As this study reports factors that significantly
      increase the risk of injury for dancers and actors, it may help to heighten
      concern with reducing the incidence of injuries to professional performers,
      theatrical students, and nonprofessionals worldwide.

PMID- 8561249
TI  - Burn-related physical impairments and disabilities in Ghanaian children:
      prevalence and risk factors.
AB  - The prevalence, and risk factors for childhood burn-related physical impairments
      and disabilities in Ghana were determined with data from mothers of burned
      children. Of 650 identified burns 113 (174%) resulted in physical impairments, 5
      (1%) resulted in physical disabilities. After multivariate adjustment, the odds
      of developing burn-related physical impairments were increased by burns with
      protracted healing (odds ratio [OR] = 5.80), burns to the head/neck (OR = 344),
      burns involving skin removal (OR = 3.04), and wound infection (OR = 2.03) and
      decreased by first aid (OR = 0.51) and maternal education (OR = 0.54). Education
      on the proper care of burns may prevent burn-related physical impairments. The
      results also underscore the link between maternal education and child morbidity.

PMID- 8561250
TI  - Capodanno Senza Danno: the effects of an intervention program on fireworks
      injuries in Naples.
AB  - To study the effects of a comprehensive, multifaceted intervention program to
      reduce fireworks-related injuries during the Italian New Year's holiday season,
      active surveillance was conducted in the 18 public emergency rooms of Naples,
      Italy, before and after implementation of the program. Preintervention data
      collected between December 24, 1992, and January 6, 1993, were compared with data
      collected during the same period in 1993-1994. The number of injuries decreased
      by 48% from 353 to 183, with the greatest declines seen among 10- to 12-year
      olds. The broad-based intervention implemented during the 1993-1994 holiday
      season appears to have substantially reduced the number of injuries.

PMID- 8561251
TI  - Assessment of a severe-weather warning system and disaster preparedness, Calhoun
      County, Alabama, 1994.
AB  - Tornado preparedness warning system effectiveness, and shelter-seeking behavior
      were examined in two Alabama areas after tornado warnings. In the area without
      sirens, only 28.9% of 194 respondents heard a tornado warning of these, 73.2%
      first received the warning from radios or television. In the area with sirens,
      88.1% of 193 respondents heard a warning, and 61.8% first received the warning
      from a siren. Knowledge of warnings, access to shelter, and education were key
      predictors for seeking shelter. Our findings indicate that installing sirens,
      providing access to shelter, and teaching appropriate responses to warnings are
      important elements of an effective disaster prevention system.

PMID- 8561252
TI  - Patterns in US medical expenditures and utilization for injury, 1987.
AB  - This article is based on data released in 1991/93 from the 1987. National Medical
      Expenditure Survey. Medical spending and utilization patterns are analyzed for 13
      major categories of injury. Medical spending on injury in 1987 was $64.7 billion
      in 1993 dollars. Nonhospitalized medically treated injuries averaged $571 in
      medical spending per case, $181 per visit, and 3.2 visits per injury. The
      prevalence-based survey estimate of medical spending on injuries during 1987 is
      10% lower than the incidence-based estimates of lifetime medical spending
      resulting from injuries in 1985.

PMID- 8561253
TI  - Why are most drowning victims men? Sex differences in aquatic skills and
      behaviors.
AB  - Men have higher drowning rates than women for most age groups. Data from a 1991
      national household survey (n = 3042) on aquatic activities were used to examine
      hypotheses about differential drowning rates by sex. Men and women were compared
      by (1) exposure to aquatic environments; (2) frequency of aquatic activities
      involving or potentially involving, submersion; (3) swimming training and
      ability; (4) aquatic risk-taking behaviors; and (5) alcohol use on or near the
      water. Men had elevated risks for exposure, risk taking, and alcohol use. It was
      concluded that several factors contribute to their relatively high drowning
      rates, including a possible interaction between overestimation of abilities and
      heavy alcohol use.

PMID- 8561254
TI  - Homicide risk among immigrants in California, 1970 through 1992.
AB  - According to the death certificates of the 65,510. California residents who died
      of homicide from 1970 through 1992, foreign-born persons are overrepresented in
      the homicides of California residents. Analysis of homicide data for 15- to 34
      year-olds (n = 38,774), who account for a majority of all homicide victims
      indicated that immigrant-to-nonimmigrant risk patterns differed by ethnicity and
      across time. During the 23-year study period, foreign-born Whites, Hispanics, and
      Asians and others were at significantly higher risk and foreign-born Blacks were
      at a statistically similar risk of homicide compared with their US-born
      counterparts (risk ratio = 2.12, 1.24, 1.72, and 0.60, respectively).

PMID- 8561255
TI  - Hydatid disease.

PMID- 8561257
TI  - Increase of birth weight following chloroquine chemoprophylaxis during the first
      pregnancy: results of a randomized trial in Cameroon.
AB  - A randomized trial was carried out from 1991 to 1993 among women attending an
      antenatal clinic in Ebolowa, Cameroon where malaria is hyperendemic and
      transmission occurs at a high level all year round. All pregnant women attending
      the clinic for their first prenatal visit between October 1991 and November 1992
      were alternately assigned to chloroquine (CQ) or control (CT) groups. Chloroquine
      was given under observation at a weekly oral dose of 300 mg. At delivery, smears
      from maternal, cord, and placental blood were made and stained with Giemsa for
      parasites. An in vivo chloroquine sensitivity investigation was carried out on
      women attending the postnatal consultation to evaluate the level of chloroquine
      resistance in the target population. The efficacy of chloroquine was moderate in
      placental infection (39.2% infected in the CQ group versus 57.8% in the CT group:
      P = 0.05), probably because of a resistance to chloroquine estimated to be 10.9%.
      In the CQ group, the mean birth weight was significantly higher (P = 0.02) and
      the proportion of low birth weight newborns was lower (10.5% versus 27.7%; P =
      0.02). A strong correlation between placental infection and birth weight was
      observed: the mean birth weight difference between infected and noninfected
      placentae was 359 g (P < 0.0001) and the proportion of low birth weight new born
      babies was 35.6% versus 5.9% (P = 0.0001). In Cameroon, in spite of a moderate
      resistance to chloroquine, this drug proved to be highly effective in increasing
      birth weight when administered to primigravidae. We therefore think such a
      prophylaxis should be recommended only to primigravidae in high transmission
      areas.

PMID- 8561256
TI  - The impact of control measures on urinary schistosomiasis in primary school
      children in northern Cameroon: a unique opportunity for controlled observations.
AB  - As part of a program to integrate schistosomiasis control into the primary health
      care system in northern Cameroon, an unexpected opportunity to undertake a
      controlled evaluation of the impact of interventions was recognized.
      Inadvertently, a large part of Mindjil, one of four assessment villages, had been
      essentially excluded from the program, creating a unique natural control. The
      prevalence of infection with Schistosoma hematobium in school-aged children was
      7% in the areas where the control program was implemented, and 71% in the
      excluded areas (P < 0.0002). High intensity infection was 1% and 26% in the two
      areas, respectively (P < 0.0002). Children in the school where the control
      interventions were implemented had a significantly lower prevalence of infection
      with Schistosoma hematobium (P < 0.005). Subjects in intervention areas
      demonstrated greater knowledge about the transmission of schistosomiasis than
      those in the control area. This study documented and quantified program impact in
      a controlled manner not usually possible in field studies and also illustrated
      how unrecognized intracultural diversity (within culture differences) in target
      populations may effect disease control programs in communities.

PMID- 8561258
TI  - Preventing hepatitis A infections in travelers to endemic areas.
AB  - In 1995, 24 million travelers from the United States are anticipated to visit
      developing countries where hepatitis A is endemic. Passive immunization with
      immune globulin, before exposure or within two weeks following exposure to the
      hepatitis A virus, protects against clinical disease in < 70-90% of immunized
      individuals. The duration of protection, measured in months, is relatively short.
      Active immunization with a single dose of inactivated hepatitis A virus vaccine
      appears to provide greater protective efficacy and, based on the persistence of
      vaccine-induced protective antibodies, should provide protection for years.
      Booster doses given between six and 12 months are likely to provide immunity that
      may persist for at least a decade. The inactivated hepatitis A vaccine approved
      for use in the United States has been clinically well-tolerated; mild transient
      soreness at the injection site is the most frequently reported adverse reaction.
      Immunization with inactivated hepatitis A vaccine is a safe and effective method
      for travelers to endemic areas to protect themselves against this infection.

PMID- 8561259
TI  - The Premise Condition Index: a tool for streamlining surveys of Aedes aegypti.
AB  - Premise inspections and treatment of the larval habitats of container-breeding
      Aedes aegypti are extremely labor intensive. Since this means of control is the
      only one available in relation to dengue fever, this report presents an effective
      approach for streamlining premise surveys in north Queensland, Australia. From a
      survey of 877 premises in Townsville, Charters Towers, and Mingela/Ravenswood in
      1990, occupier and premise variables were collected to examine any relationships
      with the presence of Ae. aegypti. Statistical modeling of these parameters using
      multiple and simple Poisson regression indicated that for both adjusted and
      unadjusted models respectively, the degree of shade and tidiness of the yard had
      strong correlations with both the proportion of positive premises and the numbers
      of infested containers therein. Condition of the house was also a significant
      variable in the unadjusted model. On this basis, the Premise Condition Index is
      proposed as a rapid assessment tool that can increase efficiency of detecting
      positive premises and containers by 270-370%. Although habitat selection by Aedes
      varies throughout the world, this approach could be used as a model for control
      of vectors of both dengue and yellow fever.

PMID- 8561260
TI  - Understanding productivity, a key to Aedes aegypti surveillance.
AB  - The objective of this work was to define criteria that could be applied to
      achieve faster, more economical, and accurate assessment of vector populations
      for control of dengue viruses. During 1989-1990, 1,349 premises were surveyed in
      Townsville, Charters Towers and Mingela/Ravenswood, Queensland, Australia. In
      each locality, 1.9-8.4% of premises contained three or more containers with Aedes
      aegypti immature forms and were designated as key premises. Comparison of surveys
      in Townsville from 1989 to 1990 indicated that positive premises (i.e., those
      with at least one container with Ae. aegypti present) were 3.22 times more likely
      to remain positive than negative houses to become positive the following year.
      The Ae. aegypti population in Townsville was seen to be totally associated with
      garden receptacles, discarded household items, and trash but one well and one
      rainwater tank were responsible for 28% of all immature forms recorded in the
      1,349 premises inspected. These breeding sites of high productivity were
      designated as key containers. At Charters Towers, Mingela, and Ravenswood,
      rainwater tanks were seen as the most important key container because although
      they constituted 13-29% of positive containers, they supported 60-63% of the
      immature forms. This study demonstrates that there is a certain degree of
      stability with regard to positive premises and that some of these, or some
      container types, contribute disproportionately to the Ae. aegypti population.
      Control programs could be made more efficient if efforts were concentrated on
      these sites of key vector productivity.

PMID- 8561261
TI  - Rickettsia tsutsugamushi infection in cell culture: antibiotic susceptibility
      determined by flow cytometry.
AB  - Recent unpublished reports from northern Thailand of severe and sometimes fatal
      cases of scrub typhus, despite appropriate antibiotic therapy, suggest that
      resistance may occur. Current antibiotic susceptibility methods that use direct
      microscopic counts of Giemsa-stained cells or mouse protection assays are slow,
      labor-intensive, and expensive. We explored the use of flow cytometry to measure
      rickettsial infection in vitro in L-929 cells treated with and without
      doxycycline, ciprofloxacin, erythromycin, and chloramphenicol. It was possible to
      detect the rickettsiae down to a level of 83% of the cells infected, mean of 37
      rickettsiae per cell, and 40% of cells with too many rickettsiae to count. This
      level of sensitivity was sufficient to determine the inhibitory effect of all
      four drugs at standard screening concentrations. At lower concentrations of
      doxycycline, flow cytometry detected inhibition of rickettsial growth at a
      concentration of 6.25 x 10(-2) micrograms/ml but not at 6.25 x 10(-3)
      micrograms/ml, suggesting that the minimum inhibitory concentration is somewhere
      between these two values. The data from this study show that flow cytometry
      permits the rapid screening of numerous rickettsial isolates for their
      susceptibility to a variety of antibiotics, but that visual counts of infected
      cells provide a more precise indication of rickettsial growth.

PMID- 8561262
TI  - Complete development of the liver stage of Plasmodium falciparum in a human
      hepatoma cell line.
AB  - Plasmodium falciparum parasites develop in the liver before being released into
      the bloodstream, where they exert the potentially lethal effects characteristic
      of malaria. Our understanding of the hepatic phase of the life cycle is limited
      by the parasite's requirement for fresh human liver cells in which to mature. In
      this work, liver parasites completed their development within a Thai human
      hepatoma cell line (HHS-102), and the presence of ring-form parasites in
      erythrocytes overlying the liver cell culture confirmed that an entire liver
      cycle was completed, culminating in the production of viable blood-stage
      parasites. The HHS-102 cell line allows investigation of the undefined liver
      stage of falciparum malaria previously unavailable in the laboratory.

PMID- 8561263
TI  - Malaria and pregnancy in Cameroonian primigravidae: humoral and cellular immune
      responses to Plasmodium falciparum blood-stage antigens.
AB  - To investigate the mechanisms underlying the increased susceptibility to malaria
      in pregnant women, we determined the level of malaria-specific immunity in
      primigravidae. Humoral and cellular in vitro responses to unpurified (a crude
      schizont extract and a gametocyte preparation) and purified (affinity-purified
      Pf155/ring-infected erythrocyte surface antigen [RESA]) Plasmodium falciparum
      proteins, an immunodominant 45/47-kilodalton antigen from Mycobacterium bovis,
      and leucoagglutinin were compared between 52 primigravidae and 52 nonpregnant
      women from a semirural area of Cameroon. In vitro cellular responses were
      investigated in terms of lymphocyte proliferation, as well as production of
      interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and IL-4. Cells from
      primigravidae exhibited a reduced proliferative response to schizont and
      gametocyte antigens, as well as to the M. bovis antigen. Conversely, the IL-2
      response to Pf155/RESA was reduced. Interleukin-4 and IFN-gamma production did
      not appear to be affected in primigravidae. Antibody levels were also similar
      between pregnant and nonpregnant women. Our results underline the importance of
      examining several parameters of T cell activation with different types of
      antigens for a correct evaluation of the ability of lymphocytes to respond to
      malaria.

PMID- 8561264
TI  - Parasitized erythrocyte membrane antigens of Plasmodium brasilianum:
      relationships with the ring-infected erythrocyte surface antigen of Plasmodium
      falciparum.
AB  - An antigen, designated here as the parasitized erythrocyte membrane antigen
      (PEMA), is present in the erythrocyte membrane surrounding all intraerythrocytic
      stages of Plasmodium brasilianum. An antibody specific for PEMA appeared in 21
      (50%) of 42 antisera from Saimiri sciureus monkeys naturally infected with P.
      brasilianum. Of these 42 sera, nine (21.4%) contained antibody to the ring
      infected erythrocyte membrane antigen (RESA); of these nine sera, six did not
      react with PEMA. Sera of humans infected with P. malariae reacted with PEMA and
      RESA in a similar pattern; i.e., of 83 antisera, 71 (85.5%) reacted with PEMA and
      30 (36%) reacted with RESA. Only one of these latter 30 sera were not reactive
      with PEMA. Of 167 sera from humans infected with P. falciparum but not P.
      malariae, 133 (79.6%) reacted with RESA; of these, 43 (25.7% of the total)
      reacted with PEMA but not RESA. Although PEMA was demonstrated with P.
      brasilianum and RESA with P. falciparum, neither PEMA or RESA could be
      demonstrated with P. malariae. Interactions of PEMA and RESA and the
      corresponding antibodies offer a method whereby the two morphologically similar
      quartan species, P. malariae and P. brasilianum, can be readily distinguished
      from each other and may furnish clues to genetic separation of the two and the
      mechanisms of interaction of quartan malaria and P. falciparum where they are
      coendemic.

PMID- 8561265
TI  - Stage-specific and species cross-reactive antibody responses in experimental
      Onchocerca infections of cattle.
AB  - Cattle experimentally infected with Onchocerca lienalis were examined by enzyme
      linked immunosorbent assay and immunoblotting to determine the degree of stage-
      and species-specificity in the immune response to infection. Levels of serum
      antibodies to antigens derived from third-stage larvae increased little after the
      first three weeks of infection, and the range of antibody specificities remained
      limited following the appearance of microfilariae (mf) in the skin. In contrast,
      antibodies to antigens from adult worms of either sex exhibited a vigorous
      response, characterized by a series of peaks arising 15-30, 79, and > 266 days
      after infection that were coincident with the timings of larval molts and the
      onset of a patent infection. Antibody specificities to the adult worms included
      many directed to molecules that were shared with other life-cycle stages, but
      some were stage-specific and others were confined to one sex. A response cross
      reactive with antigens from mf was initiated during the prepatent period, but
      antibody levels increased steeply after the infection became patent. This was
      followed by a major expansion of antibody specificities to products exclusively
      directed to mf, most notably in the range of 12-18 kilodaltons. Sera from O.
      lienalis-infected cattle cross-reacted extensively with antigens derived from O.
      volvulus adult worms and the profiles of antibody levels over time were
      indistinguishable from those obtained with O. lienalis extracts. The dominant
      response was of IgG1, although limited IgG2 and IgM reactivities were found,
      while no Onchocerca-specific IgA was detected. These results demonstrate that
      parasite development has a profound influence on the level and repertoire of
      antibodies produced during Onchocerca infections, and that extensive cross
      reactivity exists between O. lienalis and O. volvulus, lending support to the
      role of cattle models in the study of human onchocerciasis.

PMID- 8561266
TI  - Predominant CD8+ infiltrate in limb biopsies of individuals with filarial
      lymphedema and elephantiasis.
AB  - In 34 individuals with a spectrum of clinical manifestations of Bancroftian
      filariasis, we investigated whether immunoperoxidase-stained, random, superficial
      dermal biopsies could further elucidate the nature of the diffuse damage to
      superficial lymphatics that had been recently demonstrated by radionuclide
      lymphoscintigraphy. A total of 78% and 68% of limbs from patients with clinical
      disease and asymptomatic microfilaremia, respectively, contained EN4+PAL-E-
      lymphatic vessels that were abnormally dilated. The majority of subjects,
      regardless of clinical classification, had a CD3+ perivascular but not a
      perilymphatic infiltrate in tissues and no parasites were present. In contrast to
      those individuals with asymptomatic infection, a striking predominance of CD8+ T
      cells was found in the tissue of individuals with clinical disease. Tissue
      pathology consistent with cutaneous bacterial infection was not observed. The
      prominent perivenular and pericapillary mononuclear infiltrates likely indicate,
      in light of current understanding of lymphocyte recirculation, the extravasation
      of lymphocytes from the vascular circulation into the inflamed filarial tissue.

PMID- 8561267
TI  - Efficacy of oral and intravenous artesunate in male Tanzanian adults with
      Plasmodium falciparum malaria and in vitro susceptibility to artemisinin,
      chloroquine, and mefloquine.
AB  - The clinical efficacy of oral and intravenous (iv) artesunate was compared in an
      open randomized trial in 50 male adult patients with uncomplicated Plasmodium
      falciparum malaria in Kibaha, Tanzania. Oral artesunate treatment was started
      with 2 x 50 mg initially followed by 50 mg 12 hr later and then 50 mg twice a day
      for four days (total dose = 550 mg or 9.6 mg/kg). Intravenous artesunate
      administration began with 2 x 0.8 mg/kg initially followed by 0.8 mg/kg 12 hr
      later and then 0.8 mg/kg twice a day for four days (total dose = 8.8 mg/kg). The
      mean +/- SD parasite clearance times (PCTs) were nearly identical at 23.4 +/- 5.9
      hr and 24.2 +/- 7.2 hr after oral and iv administration, respectively. Mean +/-
      SD fever subsidence times (FSTs) were also similar at 18.7 +/- 8.3 hr and 21.0 +/
      4.8 hr, respectively. All patients remained negative for P. falciparum for at
      least 14 days. Recrudescence/reinfection occurred between days 21 and 28 in five
      of 25 patients (20%) after oral treatment and in four of 25 patients (16%) after
      iv treatment. The mean erythrocyte count and hemoglobin concentration were
      slightly reduced after iv treatment but remained in the normal range. Otherwise,
      there was no change in blood biochemistry, hematology, and electrocardiograms
      monitored prior to and during the last dose. It is concluded that treatment with
      oral and iv artesunate was equally efficacious and well tolerated. A 24-hr in
      vitro susceptibility test of P. falciparum to artemisinin, chloroquine, and
      mefloquine was performed in samples from all patients. The three compounds
      exhibited 100% inhibition with the exception of three isolates, which showed
      chloroquine resistance. Parameter estimates of a sigmoid Emax model (drug
      concentration at which 50% of the growth inhibition occurs [EC50]), the
      sigmoidicity factor s and EC95 fitted to the growth inhibition data differed
      between compounds and isolates, indicating different sensitivity of P. falciparum
      isolates. There was no correlation between artemisinin and mefloquine EC50
      values, while artemisinin and chloroquine EC50 values showed weak correlation (r2
      = 0.223, P = 0.006). There was no correlation between parameters describing
      clinical outcome (the PCT, the time needed for reduction of the parasite density
      to 50% and 95% of the initial parasitemia, and the FST) and those describing in
      vitro susceptibility.

PMID- 8561268
TI  - Short report: pefloxacin does not potentiate quinine efficacy against Plasmodium
      falciparum malaria.
AB  - Twenty-four patients presenting with severe Plasmodium falciparum infection at
      the Kamenge Hospital in Burundi were enrolled in a double-blind study comparing
      the efficacy of a seven-day regimen of intravenous quinine alone or in
      combination with pefloxacin. The aim of this study was to assess whether
      pefloxacin modified chloroquine efficacy or its uptake by infected erythrocytes
      as shown with other antimalarials. Pefloxacin did not modify the antimalarial
      activity of quinine, in terms of speed of parasite or fever clearance. Moreover,
      pefloxacin does not appear to interact with quinine uptake by erythrocytes in
      humans.

PMID- 8561269
TI  - A randomized, placebo-controlled trial of a two-week regimen of aminosidine
      (paromomycin) ointment for treatment of cutaneous leishmaniasis in Iran.
AB  - The effect of a two-week regimen of topical aminosidine was investigated in a
      randomized, double-blind, placebo-controlled trial of 251 selected Iranian
      patients with zoonotic cutaneous leishmaniasis. Patients underwent clinical and
      parasitologic assessment before and 15 (end of therapy), 45, and 105 days after
      starting the treatment. Aminosidine ointment was safe and well-tolerated, and
      produced significant reductions in the prevalence of parasitologically positive
      smears on days 15 and 105 (but not day 45) after treatment compared with placebo.
      However, there was no clear clinical benefit at any stage after treatment. We
      conclude that this twice a day two-week regimen of aminosidine was inadequate to
      accelerate the recovery of most cases of cutaneous leishmaniasis. However, the
      ointment did show some clear evidence of parasitologic efficacy and should now be
      studied in longer or more frequent regimens in an effort to prevent parasitologic
      relapse and thus promote clinical improvement.

PMID- 8561270
TI  - Topical application of ivermectin for human ectoparasites.
AB  - Ivermectin is used in veterinary practice against many ectoparasites and
      endoparasites and is the drug of choice for treatment of human onchocerciasis.
      This study was carried out to investigate the effect of topical application of
      this drug against human ectoparasites (Sarcoptes scabiei and Pediculus humanus
      capitis). Ivernectin was found to have a curative effect on head lice after a
      single topical application. In patients with scabies, the drug was also found to
      be effective after a single application. However, in 50% of the cases, another
      application was needed five days later.

PMID- 8561271
TI  - Short report: prevalence of hepatitis C viral antibody among Brazilian children,
      adolescents, and street youths.
AB  - The prevalence of hepatitis C antibodies (anti-HCV) was investigated in 1,378
      central Brazilian children, students, and street youths (homeless adolescents
      without family links or adolescents working in poorly paid activities). Sera were
      tested with a second generation enzyme-linked immunosorbent assay, and positive
      samples were retested by a confirmatory assay (line immunoassay). All children
      attending day care centers were anti-HCV negative. Only one (0.2%) adolescent was
      positive in the student group. However, higher positivity was found in street
      youths; four (1.0%) living at home and three (3.0%) living in the streets and
      anti-HCV antibodies. Among these, the prevalence of anti-HCV increased
      significantly with age from 0% in the 9-12-year-old group to 6.9% in the 17-20
      year-old group. Risk factors including blood transfusion, tattooing, intravenous
      drug use, and sexual intercourse with multiple partners were significantly
      associated with the presence of anti-HCV in street youths. These results indicate
      that apparently healthy children and adolescents attending day care centers or
      primary schools in central Brazil have a low exposure to HCV infection, but
      street youths in the same area are at risk for infection with this virus.

PMID- 8561272
TI  - Epidemiology of isosporiasis among persons with acquired immunodeficiency
      syndrome in Los Angeles County.
AB  - To determine factors associated with isosporiasis in persons with acquired
      immunodeficiency syndrome (AIDS) in Los Angeles County, data from the AIDS
      surveillance registry were analyzed for the eight-year period 1985-1992.
      Isosporiasis was reported in 127 (1.0%) of 16,351 persons with AIDS during the
      study period. Prevalence of infection was highest among foreign-born patients
      (3.2%), especially those from El Salvador (7.4%) and Mexico (5.4%), and in all
      persons of Hispanic ethnicity (2.9%). Persons with a history of Pneumocystis
      carinii pneumonia (PCP) were less likely than PCP-negative patients to have
      isosporiasis (0.2% and 1.4%, respectively, P < 0.01). A decrease in the
      prevalence of isosporiasis in patients negative for PCP was observed beginning in
      1989 (P = 0.02). Prevalence decreased with age (P < 0.01, by chi-square test for
      trend). After controlling for multiple factors by logistic regression,
      isosporiasis was more likely to occur in foreign-born patients than in those born
      in the United States (adjusted odds ratio [OR] = 5.8, 95% confidence interval
      [CI] 3.4, 9.9, P < 0.001) and in Hispanics than in whites (non-Hispanics)
      (adjusted OR = 3.5, 95% CI 1.7, 7.2, P < 0.001). A prior history of PCP continued
      to be negatively associated with isosporiasis (adjusted OR = 0.2, 95% CI 0.1,
      0.3, P < 0.001). Age and time remained independently associated with infection.
      These data suggest that isosporiasis among persons with AIDS in Los Angeles
      County may be related to travel exposure and/or recent immigration and that the
      use of trimethoprim-sulfamethoxazole (TMP-SMX) for PCP may effectively prevent
      primary infection or expression of latent isosporiasis. Physicians should have an
      increased index of suspicion for Isospora in AIDS patients with diarrhea who have
      immigrated from or traveled to Latin America, among Hispanics born in the United
      States, in young adults, and in those not receiving PCP prophylaxis. Food and
      water precautions should be advised and TMP-SMX prophylaxis considered for the
      prevention of Isospora infection for patients with human immunodeficiency virus
      infection who travel to Latin America and other developing countries.

PMID- 8561273
TI  - Assessing the public health importance of Schistosoma mansoni in different
      endemic areas: attributable fraction estimates as an approach.
AB  - Assessment of the public health importance of schistosomiasis mansoni is hampered
      by the nonspecificity of many of its disease symptoms. Parasitologic, clinical,
      and anamnestic data from two areas in Burundi were used to obtain estimates of
      the attributable fractions for different disease symptoms at both the population
      level and within different age strata. A large proportion of individuals had
      symptoms commonly associated with Schistosoma mansoni infection that were not
      attributable to this parasite. The clinical indicator with the best test
      efficiency was shown to be bloody diarrhea. At the population level, 35% of
      bloody diarrhea cases were attributable to S. mansoni, compared with only 9% of
      diarrhea cases without blood. The attributable fractions were age-dependent, and
      in the case of diarrhea (with and without blood), children had a higher
      proportion of cases attributable to S. mansoni infection than adults. The
      association between infection and disease symptoms also increased with the
      intensity of infection. The prevalence of morbidity attributable to S. mansoni
      was similar for all symptoms, and higher in children than adults. The estimation
      of attributable fractions provides a simple approach to quantify S. mansoni
      related morbidity, which could also be extended to both S. haematobium and S.
      japonicum. Attributable fraction estimates for these three schistosome species in
      different endemic areas would greatly aid in the assessment of the health burden
      of this parasite and the effectiveness of control programs.

PMID- 8561274
TI  - Imported echinococcosis in southern California.
AB  - A retrospective chart review conducted at two teaching hospitals in Los Angeles
      County identified 28 patients with infection due to Echinococcus granulosus
      diagnosed by positive echinococcal serology and/or tissue biopsy between January
      1981 and December 1990. Of these patients, 25 (89%) were foreign born and 19
      (68%) were immigrants from the Middle East or central Asia. Only 12 of 22
      immigrants questioned about epidemiologic risk factors described a history of
      rural residence or direct exposure to dogs in their native country. Single cysts
      of liver, lung, and soft tissue were present in six of 28 patients; multiple
      cysts in the 22 remaining patients were exclusively hepatic in 13 patients,
      exclusively pulmonary in two patients, and involved mixed sites including liver,
      lung, abdomen, central nervous system, and bone in seven patients. Natives of
      middle eastern countries currently constitute a major risk group for imported
      infection due to E. granulosus in the United States. Since their epidemiologic
      risk factors may be absent and clinical presentations varied, a high index of
      suspicion for echinococcosis is warranted in this population based solely on the
      presence of a cystic mass in liver, lung, or another organ site.

PMID- 8561275
TI  - Alcohol, hepatotropic viruses, and hepatocellular carcinoma.

PMID- 8561276
TI  - Family history of alcoholism and the mediation of alcohol intake by catalase:
      further evidence for catalase as a marker of the propensity to ingest alcohol.
AB  - Earlier studies have suggested that catalase activity (CA) may represent a
      biological marker of alcohol intake in animals and in humans. An initial study
      was designed to rule out the possibility that CA is induced as a function of
      acute alcohol intake. Subjects (n = 80) were presented with either an alcohol
      (0.5 g/kg of body weight) or control solution, and asked to provide four 100
      microliters blood samples at 0.0, 0.5, 2.0, and 24.0 hr. Results showed no
      differences in CA between individuals who had received alcohol, and controls,
      even when the effects of previous drinking history were covaried out. This lack
      of effect of acute alcohol intake on the possible induction of CA further
      supported the notion that CA may be a viable marker of alcohol intake, rather
      than the converse. In the second study, the relation between CA and alcohol
      intake was investigated in individuals with a family history (FH) of alcoholism
      (FH+), and in those without a family history of alcoholism (FH-). Subjects (n =
      607) completed the Michigan Alcoholism Screening Questionnaire, the MacAndrew
      Scale, and the Concordia University Alcohol Screening Questionnaire; answered
      questions concerning their FH for alcoholism; and provided a 100-microliters
      blood sample. Results showed that FH+ individuals had higher mean CA compared
      with FH- individuals. When individuals with FH+ were compared with those with FH
      , differences in the pattern of relation between CA and alcohol intake were
      observed. Although a significant relation between CA and alcohol intake was
      obtained for both FH- and FH+ individuals, this relation was significantly higher
      (p < 0.001) for individuals with FH+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8561277
TI  - Mitochondrial aldehyde dehydrogenase polymorphism in Asian and American Indian
      populations: detection of new ALDH2 alleles.
AB  - Genetic deficiency of the mitochondrial aldehyde dehydrogenase (ALDH2) is
      frequent in Asian peoples where it is an important factor negatively regulating
      drinking behavior. To obtain additional information on gene geography of known
      ALDH2 alleles, and look for new variants, ALDH2 genes were evaluated in a Chinese
      population from Taiwan, a Yakut population of Siberia, and in five North American
      Indian populations. A novel approach based on a single-strand conformation
      polymorphism assay, and polymerase chain reaction-directed mutagenesis was
      developed for genotyping. In the Taiwan Chinese population, the ALDH2(2) allele
      frequency was 0.319 +/- 0.025, and this allele was not detected in the Yakut
      population nor in the five North American Indian populations. However, a new
      allele, ALDH2(3), was detected in Pima Indians at a frequency of 0.044 +/- 0.022,
      and this allele was also observed in 1 of 49 Pueblo samples. ALDH2(3) is a silent
      transition 1464 G-->A, and it possibly has a wide distribution among North
      American Indians. A new subtype of the ALDH2(2) allele, designated as
      ALDH2(2Taiwan), was found in 1 of 174 Chinese from Taiwan. ALDH2(2Taiwan) is
      characterized by two G-->A transitions at bases 1486 and 1510, resulting in Glu-
      >Lys substitutions at both the 479 and 487 positions. Thus, this second
      nonconservative ALDH2 substitution occurs within the sequence of the already
      inactive ALDH2(2) allele.

PMID- 8561278
TI  - Alcohol sensitivity and smoking history in men and women.
AB  - Many studies have found genetic effects to contribute to alcoholism risk in both
      men and women. Based on preliminary evidence for shared genetic risk between
      smoking and drinking problems, a reanalysis of alcohol challenge data on 412
      Australian twins was performed to explore the possibility that smoking may
      diminish or moderate the intoxicating effects of alcohol. We found history of
      smoking to be strongly associated with self-reported intoxication after alcohol
      challenge in women (women: r = -0.44 +/- 0.08; men: r = -0.21 +/- 0.08),
      comparable with self-reported average weekly consumption of alcohol, which was
      more strongly associated in men (women: r = -0.37 +/- 0.07; men: r = -0.54 +/-
      0.06). Structural equation model-fitting indicated a strong association between
      heavy drinking and smoking, but the association between smoking and postalcohol
      intoxication remained even when the effects of heavy drinking were controlled
      for. These results prompt the question of whether smoking cigarettes directly
      influences the transition from moderate to excessive use of alcohol by
      diminishing feelings of alcohol intoxication.

PMID- 8561279
TI  - Brain atrophy and cognitive function in older abstinent alcoholic men.
AB  - We used computer-aided magnetic resonance image analysis and an age-normed
      battery of neuropsychological tests to measure brain atrophy and cognitive
      function in 14 older abstinent alcoholic men and 11 older controls in the
      expectation that these subject groups would show the greatest and most persistent
      cerebral effects consequent to chronic alcoholism. The abstinent alcoholics
      exhibited cognitive impairments (primarily in memory and visual-spatial-motor
      skills) compared with the controls. In contrast, we found no difference in global
      cerebral atrophy between the groups, although two alcoholics had extensive
      atrophy compared with all other subjects. However, there was a stronger
      association between age and ventricular dilation in the alcoholic sample compared
      with controls. We conclude that a substrate other than magnetic resonance imaging
      detectable global atrophy must underlie the persistent cognitive impairments
      evident in the sampled alcoholics. Furthermore, if there are global atrophic
      changes in the brain associated with chronic alcoholism, these effects are not
      ubiquitous and/or may be reversible in most patients with sufficient abstinence.

PMID- 8561280
TI  - Impaired delay eyeblink conditioning in amnesic Korsakoff's patients and
      recovered alcoholics.
AB  - The performance of amnesic Korsakoff patients in delay eyeblink classical
      conditioning was compared with that of recovered chronic alcoholic subjects and
      healthy normal control subjects. Normal control subjects exhibited acquisition of
      conditioned responses (CRs) to a previously neutral, conditioned tone stimulus
      (CS) following repeated pairings with an unconditioned air-puff stimulus, and
      demonstrated extinction of CRs when the CS was subsequently presented alone. Both
      amnesic Korsakoff patients and recovered chronic alcoholic subjects demonstrated
      an impairment in their ability to acquire CRs. These results indicate that the
      preservation of delay eyeblink conditioning in amnesia must depend on the
      underlying neuropathology of the amnesic syndrome. It is known that patients with
      amnesia caused by medial temporal lobe pathology have preserved conditioning. We
      have now demonstrated that patients with amnesia caused by Korsakoff's syndrome,
      as well as recovered chronic alcoholic subjects, have impaired conditioning. This
      impairment is most likely caused by cerebellar deterioration resulting from years
      of alcohol abuse.

PMID- 8561281
TI  - Thyrotropin and prolactin responses to thyrotropin-releasing hormone in young men
      at high or low risk for alcoholism.
AB  - A reduced thyrotropin (TSH) response to TSH-releasing hormone (TRH) has been
      reported in a portion of abstinent alcoholic men without evidence of cirrhosis of
      the liver. It is not known whether this neuroendocrine change is a precursor of
      alcoholism or a sequelae of heavy alcohol consumption. Three of four published
      studies have found evidence for differences in TRH-induced TSH response in
      subjects at high risk for alcoholism, based on family history, compared with
      subjects at low risk for alcoholism. To test further the hypothesis that the TRH
      induced TSH response is a vulnerability marker for alcoholism, we tested 25 young
      men with an alcoholic father [family history-positive (FHP)] and matched them, on
      alcohol consumption, to 25 young men with no identified first- or second-degree
      relatives with alcoholism [family history-negative (FHN)]. FHP subjects were
      further categorized based on whether their father had shown signs of alcohol
      problems before age 25 years (FHP-Early, n = 10) or after age 24 years (FHP-Late,
      n = 12). FHP subjects did not differ from FHN subjects in their baseline levels
      of thyroid hormones, glucose, cortisol, or TSH. However, the distribution of TSH
      responses in the FHP subjects was skewed toward lower values, compared with FHN
      subjects (p = 0.12). Furthermore, FHP-Late subjects had lower TSH responses than
      FHN subjects (p = 0.02), whereas the TSH response of FHP-Early subjects was not
      different from FHN subjects. Prolactin responses to TRH were similar across all
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8561282
TI  - Alcohol hangover and managerial effectiveness.
AB  - Twenty-one male managers who normally drink moderate amounts of alcohol
      participated in a placebo-controlled, double-blind, cross-over experiment.
      Subjects consumed either placebo or alcoholic drinks to attain a breath alcohol
      level of 0.10 during the evening before participation in Strategic Management
      Simulations. By the time of arrival at the simultaion laboratory on the following
      morning, breath alcohol levels were measured at 0.00. Questionnaire responses
      indicated considerable hangover discomfort. Responses to semantic differential
      evaluative scales suggested that research participants evaluated their own
      managerial performance in the simulation setting as impaired. However, multiple
      (validated) measures of decision-making performance obtained in the simulation
      task did not show any deterioration of functioning. Previous research had shown
      considerable performance decrements in the same task setting, while blood/breath
      alcohol levels ranged from 0.05 through 0.10%. Apparently, complex decision
      making competence by persons who normally consume moderate amounts of alcohol may
      not be impaired by hangover caused by intoxication during the previous evening
      that remains at or below a blood alcohol level of 0.10.

PMID- 8561283
TI  - Methanol in human breath.
AB  - Using proton transfer reaction-mass spectrometry for trace gas analysis of the
      human breath, the concentrations of methanol and ethanol have been measured for
      various test persons consuming alcoholic beverages and various amounts of fruits,
      respectively. The methanol concentrations increased from a natural
      (physiological) level of approximately 0.4 ppm up to approximately 2 ppm a few
      hours after eating about 1/2 kg of fruits, and about the same concentration was
      reached after drinking of 100 ml brandy containing 24% volume of ethanol and
      0.19% volume of methanol.

PMID- 8561284
TI  - Effect of alcohol use on allograft rejection rates after liver transplantation
      for alcoholic liver disease.
AB  - Alcoholic liver disease is a major cause of liver disease and has become an ever
      increasing indication for liver transplantation (LTx). Follow-up studies have
      reported a higher rate of alcohol recidivism in patients transplanted for
      alcoholic hepatitis, compared with those transplanted for endstage alcohol
      associated cirrhosis. It is assumed widely that recurrent alcohol use is
      associated with reduced compliance with immune suppression and, as a result, an
      increased risk of graft rejection and loss. To assess this question, 209
      alcoholic patients transplanted for either alcoholic hepatitis with cirrhosis or
      cirrhosis alone between January 1, 1986 and December 31, 1991 were followed, with
      a mean follow-up of 4.4 +/- 0.6 years. There were 175 episodes of acute cellular
      rejection (ACR) that occurred in 137 patients, for an overall rejection rate of
      83.7% or at a rate of 1.25 episodes/patient with rejection. The rate of ACR was
      three times as great in those who remained alcohol-abstinent (2.24
      episodes/patient), compared with those who admitted to continued alcohol use
      (0.75 episodes/patient) (p < 0.01). A total of 33 episodes of chronic rejection
      occurred in 26 patients, for an overall rate of 12.4%. As was the case for ACR,
      the chronic rejection rate was greater among those who were continuously alcohol
      abstinent, compared with those who intermittently used alcohol after successful
      LTx. There were no differences in the mean FK 506 or cyclosporin A levels in the
      groups with and without a rejection episode at the time the rejection episode was
      documented by liver biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8561285
TI  - Retrospective self-report of alcohol consumption: test-retest reliability by
      telephone.
AB  - The Timeline Follow-Back (TLFB) is an interview technique for obtaining detailed
      retrospective self-reports of alcohol consumption with excellent reliability for
      various composite variables when both administrations are in person. Because the
      telephone offers practical advantages over face-to-face interviewing for follow
      up assessments in longitudinal studies of problem drinkers, this study was
      undertaken to compare the test-retest reliability of a 12-week TLFB interview
      when the second administration was by telephone to that when the second interview
      was in person. In addition, because the reliability of the TLFB has been
      previously assessed using composite variables, we examined the reliability of the
      TLFB at the item level. Research participants were 30 adult medical patients who
      drank frequently, and 75 college students who were problem drinkers. Test-retest
      reliability as measured by intraclass correlation was generally high, 0.79 or
      greater for the number of days of drinking > 6 standard drinks, 0.90 or greater
      for the number of abstinent days, and 0.80 or greater for the greatest number of
      drinks consumed on any 1 day, in both the most recent 4-week interval and in the
      entire 12-week interval. Test-retest correlation coefficients for composite
      variables derived from the interview data were not systematically affected by
      whether the second interview was in person or by telephone. Furthermore, item
      level correlations were also substantial. Findings support the use of the
      telephone for follow-up interviews, potentially reducing costs of longitudinal
      studies and facilitating multisite studies with centralized data collection, and
      lend further general support to the reliability of the TLFB.

PMID- 8561286
TI  - Assessing gender interactions in the prediction of mortality in alcoholic men and
      women: a 20-year follow-up study.
AB  - This study investigates the predictors of mortality in 259 male and female
      alcoholics who were psychiatrically hospitalized between 1967 and 1968 and
      followed for > 20 years. The findings showed that, in addition to age, marital
      status, medical complications, and non-antisocial personality comorbidity were
      important independent predictors of time to death. Data pointed to gender
      interactions, in that marital disruption tended to be a stronger predictor of
      mortality in men, and delirium tremens tended to be a stronger predictor of
      mortality in women. Knowing and understanding that certain events and processes
      may differentially affect the survival of male and female alcoholics will allow
      for the development of more individualized and gender-specific therapeutic
      interventions.

PMID- 8561287
TI  - Hepatitis C virus in alcoholic patients with and without clinically apparent
      liver disease.
AB  - A high prevalence of antibodies to the hepatitis C virus (anti-HCV) has been
      demonstrated among patients with alcoholic liver disease, whereas the prevalence
      of HCV viremia in these patients remains uncertain. The aims of this study were
      to determine the prevalence of anti-HCV in alcoholic patients both with and
      without clinically apparent liver disease and to determine the presence of HCV
      RNA in those patients who tested positive for anti-HCV by RIBA II (Chiron
      Corporation, Emeryville, CA). One hundred male patients consecutively admitted to
      an alcoholic rehabilitation program were included. Group 1 was comprised of 40
      patients with clinically apparent liver disease. Group 2 was comprised of 60
      patients without clinically apparent liver disease. Anti-HCV was performed by a
      second-generation ELISA assay and confirmed by RIBA II. HCV RNA was performed by
      Quantiplex assay (Chiron Corporation) and a nested reverse transcriptase
      polymerase chain reaction. No significant differences were found between the two
      groups with regards to age, quantity and duration of alcohol intake, or accepted
      risk factors for HCV. The overall prevalence of anti-HCV in our patients was 23%,
      with 43% of these in group 1 and 10% in group 2. HCV RNA tested positive in 94%
      of the anti-HCV-positive patients in group 1 and in 67% of the anti-HCV-positive
      patients in group 2. These data suggest that HCV infection is an important
      cofactor in the pathogenesis of liver disease among alcoholic patients.

PMID- 8561288
TI  - Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and
      relapsed alcoholics.
AB  - Chronic alcoholism is associated with smaller volumes of cortical gray matter and
      white matter and a complementary increase in brain cerebrospinal fluid (CSF)
      volumes, relative to age norms. This longitudinal study quantified the extent of
      brain volume changes associated with abstinence and drinking at three time points
      in chronic alcoholics. We obtained magnetic resonance imaging (MRI) on 58
      alcoholic men after an average of 12 days (MRI-1) and 32 days (MRI-2) of
      sobriety. In addition, 58 healthy control subjects were scanned at a comparable
      interval. At MRI-3, 11 controls and 39 alcoholics were rescanned, 2-12 months
      after MRI-2; 19 alcoholics had abstained, and 20 had resumed drinking. Axial MRI
      slices were segmented into cortical gray matter, white matter, and CSF and summed
      over seven slices; lateral and third ventricular volumes were also estimated. MRI
      volume changes were corrected using an estimate of interscan measurement error
      caused by head positioning differences, and then divided by the interval to yield
      rates of change (slopes). From MRI-1 to MRI-2, the alcoholic group showed
      declines in CSF volumes of the lateral ventricles and posterior cortical sulci,
      and a trend toward an increase in anterior cortical gray matter volume relative
      to the control group. From MRI-2 to MRI-3, third ventricular volumes decreased in
      the abstainers relative to the relapsers and controls; cortical white matter
      volume decreased in the relapsers. In the relapsers, lifetime consumption of
      alcohol (as of MRI-1) predicted later vulnerability to white matter volume
      decline and third ventricular enlargement with resumption of drinking. These data
      suggest that improvement in cortical gray matter, sulcal, and lateral ventricular
      volumes occur early in the course of abstinence, and that improvement in third
      ventricular volume appears later with continued abstinence.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8561289
TI  - Style, consumption, and problem drinking: a measurement model.
AB  - Yu and Williford (J. Drug Issues 22:75-90, 1992) report from a structural study
      that drinking style is the best predictor of problem drinking. This study further
      examines a measurement model on drinking style, alcohol consumption, and problem
      drinking. Four measures are specified for drinking style, three for alcohol
      consumption, and two for problem drinking. The maximum-likelihood procedure
      through the LISREL program is used to reproduce the observed correlations by
      allowing correlations among systematic measurement errors. Strong associations
      are noted among drinking style, alcohol consumption, and problem drinking. The
      analysis suggests that the style of drinking should be included in research on
      problem drinking. Implications of the findings and future research issues are
      discussed.

PMID- 8561290
TI  - Abnormalities of the corpus callosum in children prenatally exposed to alcohol.
AB  - For 20 years, it has been known that fetal alcohol syndrome (FAS) is associated
      with abnormal brain development. Early autopsy studies point to the corpus
      callosum as one area affected by heavy alcohol exposure. Little is known,
      however, about the integrity of the brain in alcohol-exposed children who survive
      the perinatal period. This study was designed to assess the corpus callosum in
      living children exposed to high doses of alcohol prenatally. Thirteen children
      with histories of significant prenatal alcohol exposure and 12 normal control
      children were evaluated using magnetic resonance imaging. Using the midsagittal
      section, images were measured for the area of the corpus callosum using a
      computer-assisted measurement technique. In addition to the overall area, five
      equiangular regions were determined for each corpus callosum. Of the 13 alcohol
      exposed children assessed, two had agenesis of the corpus callosum. The remaining
      alcohol-exposed children had significantly smaller overall callosal areas, as
      well as smaller regional areas of four of the five callosal regions, when
      compared with the normal control children. Importantly, when corrected for brain
      size, three of the five callosal regions were still smaller in the alcohol
      exposed children, although overall area of the corpus callosum was no longer
      significantly different. These results suggest that prenatal exposure to high
      levels of alcohol is associated with abnormalities of the corpus callosum. They
      verify callosal agenesis in children with FAS, which previously had only been
      noted in autopsy reports.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8561291
TI  - Carbohydrate-deficient transferrin as a marker of alcohol abuse: relationship to
      alcohol consumption, severity of liver disease, and fibrogenesis.
AB  - Carbohydrate-deficient transferrin (CDT) measurements have been widely examined
      as a marker of excessive alcohol consumption, yet the information on the
      sensitivity of this method has remained controversial. In addition, little is
      known of the relationship of this marker and the severity of alcoholic liver
      disease (ALD). To clarify these issues, we analyzed serum samples from 373
      alcohol abusers, including 200 problem drinkers with no apparent liver pathology,
      173 patients with clinical or morphological evidence of ALD, and 42 healthy
      controls. CDT was analyzed by anion-exchange chromatography followed by
      radioimmunoassay. At a specificity of 100%, the sensitivity of CDT was 36% in
      problem drinkers reporting a mean of 710 +/- 80 (mean +/- 2SE) g of ethanol/week,
      as compared with the sensitivities of 44% and 35% for gamma
      glutamyltranspeptidase (GGT) and mean corpuscular volume (MCV), respectively. In
      a subgroup of problem drinkers (n = 51) with the highest ethanol intakes (1160 +/
      180 g of ethanol/week) and severe dependence, the sensitivity of CDT increased
      to 64%, compared with 55% for GGT and 39% for MCV. In ALD, the CDT values were
      significantly higher than in the alcoholics with nonliver pathology. However,
      when such patients were classified according to the clinical, laboratory, and
      morphological severity of liver disease, CDT was found to be primarily elevated
      in those with the early stage of ALD, such that there was a significant negative
      correlation between CDT and the combined morphological index of disease severity
      (rs = -0.315, p < 0.05). ALD markers of fibrogenesis were elevated more
      frequently than CDT, showing significant positive correlations with the indices
      of disease severity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8561292
TI  - Voice of the victims.
AB  - Over the past 10 years, I have been privileged to conduct educational forums for
      audiences containing many recovering alcoholics or otherwise chemically dependent
      persons. In these forums about the addictive diseases and their treatment and
      research possibilities, significant interaction with the audience members occurs.
      During these interactions, certain anecdotal phenomena seem to predominate. The
      repetitive nature of these reports suggests the need for systematic
      investigation. As with editorial comments in major medical journals, observed
      phenomena and unanswered questions from the victims can be valuable in the
      generation of testable hypotheses. Perhaps the ideas presented herein will be
      useful in the development of future research on alcohol abuse and alcoholism.

PMID- 8561293
TI  - Gonadotropin-releasing hormone mRNA and gonadotropin beta-subunit mRNA expression
      in the adult female rat exposed to ethanol in utero.
AB  - Previous studies have demonstrated that exposure of female rats to ethanol in
      utero results in long-term deficits in reproductive function, including a delayed
      onset of puberty and an early onset of acyclicity. In the present studies, we
      determined if changes in reproduction are correlated with changes in gonadotropin
      releasing hormone (GnRH) mRNA expression in the brain or gonadotropin subunit
      mRNA expression in the anterior pituitary gland. We used in situ hybridization
      histochemical techniques to examine the density of GnRH mRNA and the distribution
      of GnRH mRNA-containing cells in the basal forebrain, and reverse transcription
      polymerase chain reaction (RT-PCR) to quantitate the beta-subunit mRNA of
      luteinizing hormone (LH beta) and follicle-stimulating hormone (FSH beta) in the
      anterior pituitary gland of adult (3 months of age) fetal alcohol-exposed (FAE)
      female rats. For GnRH mRNA measurements, animals were gonadectomized 4 days
      before use. Three groups of animals were examined. FAE females were derived from
      pregnant dams fed a liquid diet containing 35% ethanol-derived calories from
      gestational day 14 until parturition. Dams of control animals were either pair
      fed (PF) an isocaloric diet with sucrose substituted for ethanol or maintained on
      normal laboratory rat chow [chow-fed (CF)]. Serial blood samples taken by
      indwelling right atrial cannulae demonstrated significantly smaller pulses of LH
      (p < 0.05) and FSH (p < 0.05) in ovariectomized FAE females at 3 months of age,
      compared with PF and CF controls. Distribution of GnRH mRNA-containing cells was
      mapped throughout the forebrain, and the number of autoradiographic silver
      grains/cell was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8561294
TI  - Alcohol ingestion impairs host defenses predisposing otherwise healthy mice to
      Pneumocystis carinii infection.
AB  - Pulmonary infection with Pneumocystis carinii, an opportunistic pathogen, is
      associated with a variety of immunosuppressive states, including human
      immunodeficiency virus infection. We hypothesized that alcohol ingestion might
      compromise host defenses against this pathogen and, in an immunocompromised host,
      increase the severity of infection. This hypothesis was tested in both acute and
      chronic ethanol-treated normal and CD4+ T-cell-depleted mice challenged with P.
      carinii organisms. Normal and CD4+ T-cell-depleted mice were given an
      intraperitoneal injection of ethanol or saline 0.5 hr before P. carinii challenge
      and killed 3 hr later for bronchoalveolar lavage. Acute alcohol treatment
      decreased significantly tumor necrosis factor (TNF) activity and the number of
      polymorphonuclear leukocytes (PMNLs) recovered in the lavage in response to the
      pathogen. Depletion of CD4+ T-cells did not potentiate the effect of alcohol on
      the early inflammatory response to the pathogen any further. In normal animals,
      in vivo interferon (IFN)-gamma pretreatment augmented significantly the P.
      carinii-stimulated lung TNF response and PMNL recruitment. However, IFN-gamma
      pretreatment prevented the alcohol-induced suppression of TNF secretion without
      affecting the PMNL recruitment. The effect of chronic alcohol consumption on the
      severity of infection was studied in long-term, alcohol-fed normal and CD(4+)
      depleted mice challenged with P. carinii organisms. Lung histopathology showed
      that P. carinii infection was present in > 60% of the alcohol-fed mice and in
      none of the controls. Also, a significantly higher number of PMNLs were recovered
      in the lavage fluid of alcohol-fed mice with persistent infection.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8561295
TI  - In utero ethanol exposure retards growth and alters morphology of cortical
      cultures: GM1 reverses effects.
AB  - Ethanol, a developmental neurotoxin, alters plasma membranes' physicochemical
      properties affecting embryogenesis, cell migration, differentiation, and
      synaptogenesis. In a previous study using a model for fetal alcohol effects, GM1
      ganglioside treatment was shown to reduce ethanol-induced accumulation of
      endogenous GM1 and fatty acid ethyl esters in rat fetuses. The present study was
      initiated to define further the in utero effects of ethanol and the capacity of
      GM1 treatment to ameliorate such effects. Wistar dams were exposed to ethanol
      (intragastrically) on gestation day (GD) 7 and GD8 and GD13 and GD14. GM1
      ganglioside (10 mg/kg, im) was given 24 hr before ethanol administration.
      Cortical cultures were derived from GD15 and GD20 fetuses. GM1, which is highly
      localized on the cellular plasma membrane outer surface of CNS cells, was used as
      a marker molecule to assess cell integrity. Cholera toxin/antitoxin/fluorescence
      immunohistochemistry was used to localize GM1. Results indicate that the brief in
      utero exposure to ethanol affected cell growth and morphology. A marked
      retardation of cell development and arborization was observed as early as 24 hr
      after plating. Ethanol-exposed cells evidenced considerably altered GM1
      localization. Such alterations likely reflect losses of membrane integrity. These
      in utero ethanol-induced pathologies are remarkably diminished in cultures
      derived from ethanol-exposed fetuses of dams treated with GM1.

PMID- 8561296
TI  - Bidirectional selective breeding for ethanol effects on locomotor activity:
      characterization of FAST and SLOW mice through selection generation 35.
AB  - Increased recognition of the advantages of genetic animal models has led to
      heightened interest in their use and development. A replicated bidirectional
      selective breeding project has produced lines of mice that differ in their
      locomotor responses to 2.0 g/kg ethanol. FAST-1 and FAST-2 mice are highly
      stimulated by ethanol (EtOH), whereas SLOW-1 and SLOW-2 mice are either not
      affected or respond with locomotor depression. Current heritability estimates
      indicate that approximately 6-8% of the response variance in the FAST lines and 2
      10% of the response variance in the SLOW lines is of additive genetic origin.
      Little systematic response to selection has occurred in recent generations, which
      implies that the limits of selection have been reached. Analysis of saline
      activity over 35 generations of selection indicates that baseline activities have
      not changed during the course of selection in three of the lines, whereas
      baseline activity of FAST-1 mice has increased slightly. In EtOH dose-response
      studies (0.5-3.0 g/kg), FAST mice had biphasic dose-response curves, whereas the
      locomotor activity of SLOW mice was either unaffected or depressed by all doses
      of EtOH. In addition, FAST mice spent more time in motion, traveled farther per
      movement, traversed greater distances in the center of the test chamber, and
      ambulated more quickly than SLOW mice when given EtOH. FAST and SLOW mice
      differed in EtOH clearance rates; however, the differences were slight relative
      to the large difference in locomotor response. We encourage the use of FAST and
      SLOW mice to investigate neurophysiological factors underlying sensitivity to the
      behavioral effects of EtOH, with a view to further testing of the postulated
      homology between locomotor stimulant effects and addiction potential of drugs of
      abuse.

PMID- 8561297
TI  - Ethanol suppresses growth hormone-mediated cellular responses in liver slices.
AB  - Previous studies indicate that both acute and chronic ethanol administration
      inhibit protein synthesis and decrease the secretion of insulin-like growth
      factor-1 (IGF-1). Although IGF-1 synthesis and secretion are regulated by growth
      hormone secretion from the pituitary gland, we assessed whether ethanol inhibits
      tissue response to growth hormone. Liver slices from male Sprague-Dawley rats
      were prepared, placed into F-12 media, and incubated at 37 degrees C with
      [3H]leucine, and either 0.25 or 1 nM rat growth hormone and 0, 37 (physiological
      levels), or 175 mM (toxic levels) ethanol. Tissues were removed at 0, 15, 30, and
      60 min. Protein synthesis increased linearly during this time period, and
      administration of growth hormone (1 nM) significantly increased protein synthetic
      rate by 48% (p < 0.01), whereas addition of 37 or 175 mM ethanol attenuated the
      effects of growth hormone (p < 0.01). Analysis of IGF-1 mRNA indicated a 2-fold
      increase in response to growth hormone (p < 0.01), whereas ethanol administration
      decreased the growth hormone-induced rise of IGF-1 mRNA. Ethanol (175 mM)
      inhibited the release of IGF-1 into the media (p < 0.05). Ethanol did not alter
      growth hormone receptor binding, and exposure of tissue slices to ethanol did not
      influence the number of growth hormone receptors or the affinity of growth
      hormone for its receptor. Our results demonstrate that (1) growth hormone is a
      potent acute regulator of IGF-1 mRNA and IGF-1 peptide release, (2) ethanol
      inhibits growth hormone-induced protein synthesis and induction of IGF-1 gene
      expression, and (3) the inhibitory effects of ethanol on growth hormone occur
      without changing growth hormone receptor number or binding characteristics. We
      conclude that ethanol suppresses growth hormone-induced signal transduction,
      resulting in a decrease in IGF-1 gene expression.

PMID- 8561298
TI  - Chronic prenatal ethanol exposure alters the normal ontogeny of choline
      acetyltransferase activity in the rat septohippocampal system.
AB  - In animal models of fetal alcohol syndrome (FAS), the hippocampus has been shown
      to be especially sensitive to the effects of prenatal ethanol exposure,
      exhibiting neuronal loss and alterations in neuritic process elaboration. We have
      characterized the influence of chronic prenatal ethanol treatment (CPET) on the
      postnatal expression of choline acetyltransferase (ChAT) in the hippocampus and
      the septal area that contains neurons that provide the primary cholinergic
      innervation to the hippocampus. On gestation days 1-22, pregnant rats were either
      fed an ethanol-containing liquid diet, pair-fed a calorically equivalent sucrose
      containing diet, or given rat chow ad libitum. In Chow control animals, the
      ontogenetic progression of ChAT activity in the septal area and hippocampus was
      characterized by a significant period of upregulation during the 2nd and 3rd
      postnatal weeks, exhibiting and an approximate 5-fold increase (septal area) and
      7-fold increase (hippocampus) by postnatal day 21 (P21). At P14, ethanol exposure
      reduced septal and hippocampal ChAT activity levels, compared with those of pair
      fed offspring. ChAT activity reached control levels by P21 in ethanol-exposed
      pups, suggesting that the earlier decline in activity may reflect a delay in the
      ontogenetic upregulation. In addition, there was a trend toward increased septal
      and hippocampal ChAT activities at P1 and P7 in both liquid diet groups. This
      liquid diet-stimulated increase may mask the effects of ethanol on early
      postnatal ChAT expression in the septohippocampal system. The results suggest
      that prenatal ethanol exposure may influence factors that regulate the
      developmental expression of ChAT in the septohippocampal system.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8561299
TI  - Synapse-to-neuron ratio in the lateral geniculate nucleus of rats exposed
      chronically to ethanol.
AB  - Effects of chronic ethanol exposure on synapse-to-neuron ratio in the rat lateral
      geniculate nucleus were investigated. Male Sprague-Dawley rats were exposed to
      ethanol, using the Lieber-DeCarli liquid diets, for 4 months starting at the age
      of 5 weeks. Brains were perfusion-fixed, and the region containing the dorsal
      lateral geniculate nucleus was cut into slabs (500 microns thick) that were epoxy
      resin-embedded. From each rat, three slabs containing the structure were serially
      sectioned for electron microscopy. Using the double disector method, the study
      shows an unaltered synapse-to-neuron ratio in ethanol-treated rats when compared
      with controls. The findings are in agreement with previous studies on the visual
      system using the same exposure model. In contrast, a previous study has shown
      that the synapse-to-neuron ratio in locus ceruleus of ethanol-treated rats is
      reduced by 50%. Other studies have shown that, whereas the glutamatergic NMDA
      receptor is very sensitive to ethanol, the kainate/AMPA type of receptor is very
      much less so. Thus, the difference in ethanol-induced synapse elimination between
      the two regions may reflect this different sensitivity of the glutamatergic
      receptors, which are of the kainate/AMPA type in the lateral geniculate nucleus
      and of the NMDA type in the locus ceruleus.

PMID- 8561300
TI  - Low-density lipoprotein reconstituted with fatty acid ethyl esters as a
      physiological vehicle for ethyl ester delivery to intact cells.
AB  - Fatty acid ethyl esters (FAEEs), esterification products of ethanol and fatty
      acids, have been found selectively in the organs damaged by ethanol abuse, and on
      that basis have been implicated as contributors to ethanol-induced organ damage.
      To directly assess the cytotoxic potential of FAEEs with intact cells in a
      physiological system, solubility must be achieved for these highly nonpolar
      lipids in aqueous medium. After ethanol ingestion, FAEEs can be found within low
      density lipoproteins (LDLs). Therefore, to achieve solubility with FAEEs bound to
      a naturally occurring lipid carrier, we developed a method for FAEE
      solubilization and delivery to cells in culture. We synthesized radiolabeled
      FAEEs and incorporated them into human LDL particles that bind to LDL receptors
      and deliver FAEEs to intact cells. Ethyl palmitate and ethyl oleate were
      incorporated into LDLs yielding molar ratios of FAEEs to LDLs of 2,153 +/- 249
      and 4,208 +/- 403, respectively. LDL reconstituted with FAEE had the same
      electrophoretic mobility on agarose gel electrophoresis as native LDL, indicating
      that the reconstituted LDL (rLDL) was not oxidatively modified. Quantitative
      analysis of the solubilization of FAEEs in aqueous medium was investigated by
      adding FAEEs to tissue culture medium either directly or reconstituted in LDL at
      a concentration of 27 microM. The percentage of FAEE quantitated was 40.0 +/-
      2.5% and 89.3 +/- 0.6% for FAEEs added directly and in rLDLs, respectively. After
      sterile filtration of these two media, the percentage of FAEE that remained was
      11.8 +/- 1.3% (direct addition) and 74.9 +/- 1.3% (addition within rLDL), further
      demonstrating that the LDL particle did solubilize the FAEE.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8561301
TI  - Sucrose, ethanol, and sucrose/ethanol reinforced responding under variable
      interval schedules of reinforcement.
AB  - Adding sweeteners to ethanol solutions is a common method of inducing rats to
      consume ethanol. However, it has usually been assumed that it is the sweet taste
      and/or the calories contained in the sweet solution that controls consumption.
      The present experiment examined the role of ethanol in controlling responding
      reinforced by ethanol or an ethanol/sucrose mixture compared with sucrose
      solutions of various concentrations. After initiation to self-administer 10%
      (v/v) ethanol using the sucrose-substitution method, rats were trained to respond
      under a concurrent VI 5" VI 5" schedule. During one condition, responding on one
      lever was reinforced by the presentation of 10% ethanol, and responding on a
      second lever was reinforced by water or one of the following sucrose solutions:
      1% (w/v), 1.5%, 2%, 2.5%, 3%, and 5%. During a subsequent condition, responding
      reinforced by a 10% ethanol/2% sucrose mixture was compared under the concurrent
      schedule with responding reinforced by water, 2%, 2.5%, 3%, 5%, or 10% sucrose
      (w/v). The results indicated that the ethanol or ethanol/sucrose mixture
      maintained more responding than did sucrose solutions that were sweeter. Data
      support the conclusion that, after initiation, the taste and/or pharmacological
      effects of ethanol had become an important component of the reinforcing stimulus
      independent of the sweetener.

PMID- 8561302
TI  - Combined inhibitory effects of ethanol and adenosine on the responses of rabbit
      platelets to thrombin.
AB  - We have previously shown that acutely administered ethanol, resulting in blood
      alcohol concentrations of 40-90 mM, inhibits experimentally induced arterial
      thrombosis in rabbits. This inhibition by ethanol in vivo is more pronounced than
      that observed on stimulated platelets in vitro, when a similar concentration of
      ethanol is added before an aggregating agent. It may be, then, that ethanol has
      combined effects in vivo with other inhibitors of platelet function. Adenosine
      has been found to be an important mediator of some of the in vivo effects of
      ethanol, and we investigated whether ethanol has combined inhibitory effects with
      adenosine on thrombin-stimulated platelet responses in vitro. Aggregation and
      secretion of [14C]serotonin from washed, prelabeled rabbit platelets, pretreated
      with aspirin, were studied. Maximal aggregation induced by 0.15 units thrombin/ml
      was slightly inhibited by 87 mM ethanol; secretion of serotonin was reduced from
      24% to 12%. However, when thrombin-induced aggregation was significantly reduced
      by 1 microM adenosine, ethanol, at 44 and 87 mM, further inhibited aggregation.
      Secretion of [14C]serotonin was reduced to < 3%, with the combination of
      adenosine and the higher concentration of ethanol. Ethanol did not increase
      platelet cyclic AMP (cAMP) above basal levels, nor did it affect the increase in
      cAMP caused by adenosine. The adenosine receptor antagonist, 8
      phenyltheophylline, at 1 microM, blocked the inhibitory effects of adenosine on
      platelet responses and prevented the adenosine-induced increase in cAMP.
      Unexpectedly, however, 8-phenyltheophylline (1-2 microM) did not completely block
      the combined inhibitory effects of ethanol and adenosine; this incomplete
      reversal was not associated with increases in cAMP over basal levels.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8561303
TI  - Effects of prenatal ethanol exposure and stress in adulthood on lymphocyte
      populations in rats.
AB  - The present study was undertaken to assess the possible interactive effects of
      prenatal ethanol exposure and stress in adulthood on lymphocyte populations in
      rat offspring, and to examine differential vulnerability of males and females to
      these challenges. Male and female offspring from prenatal ethanol-exposed (E),
      pair-fed, and ad libitum-fed control conditions were exposed to a 3-week chronic
      intermittent stress regimen in adulthood. Animals were exposed to two of six
      different stressors daily, one each at random times in the morning and afternoon,
      with the same pair of stressors being repeated every 4 days. Following the 3-week
      stress period, lymphocytes from four compartments (peripheral blood, spleen,
      thymus, and cervical lymph nodes) were analyzed for expression of differentiation
      antigens. Data demonstrate that, whereas a number of the effects of prenatal
      ethanol on lymphocyte populations appeared to be nutritionally mediated, the
      additional challenge of exposure to stressors differentially affected animals
      exposed to ethanol prenatally and appeared to have effects primarily in male
      offspring. Stressed E males had a greater reduction in the number of pan T-cells
      in the thymus and peripheral blood, compared with nonstressed E males, but showed
      an increased peripheral blood pan T-antigen expression. Stressed E males also had
      reduced numbers of peripheral blood CD4+ T cells compared to nonstressed E males
      [corrected].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8561304
TI  - Effect of chronic alcoholism on human muscle glycogen and glucose metabolism.
AB  - To determine the effect of alcohol on carbohydrate metabolism, 48 human muscle
      biopsies from chronic alcoholics were studied. The level of glycogen and the
      activities of the enzymes catalyzing glycogen and glucose metabolism were
      analyzed. Chronic alcohol intake produced an increase in glycogen concentration
      and a decrease in pyruvate kinase activity before the first signs of myopathy
      appeared. When myopathy was present, glycogen decreased. These changes may
      contribute to the decline in skeletal muscle performance in these patients.

PMID- 8561305
TI  - Aldehyde dehydrogenase activities in the brains of rats and mice genetically
      selected for different sensitivity to alcohol.
AB  - Aldehyde dehydrogenase activity in brain has been studied for many years.
      However, the question of its role in the actions of ethanol in the brain has not
      been resolved. We have utilized mice and rats selectively bred for sensitivity or
      resistance to the initial hypnotic effects of ethanol to gain some insight into
      the possible involvement of brain aldehyde dehydrogenase in the actions of
      ethanol. We compared the levels of aldehyde dehydrogenase activity in the brains
      of these selected lines of rodents by histochemical methods. It was found that,
      although aldehyde dehydrogenase activity was detected in many areas of the brain,
      only in the cerebellar Purkinje cells was there a difference between sensitive
      and resistant lines of mice or rats. The resistant lines (Short Sleep mice and
      Low Alcohol Sensitive rats) had statistically higher levels of aldehyde
      dehydrogenase than did the sensitive lines (Long Sleep mice and High Alcohol
      Sensitive rats). Although this does not prove that aldehyde dehydrogenase or
      aldehydes are involved in the central actions of ethanol, it provides another
      piece of evidence in this direction.

PMID- 8561306
TI  - Cyanamide-associated alcoholic liver disease: a sequential histological
      evaluation.
AB  - This is the first study that we are aware of that followed the histopathological
      progression of the liver disease that was caused by the combination of both
      chronic alcohol use and cyanamide, an antidipsotropic agent. Two sequential liver
      biopsy specimens were obtained on 29 alcoholics who relapsed with varying
      histories of cyanamide treatment. Cyanamide induced ground-glass inclusions
      (GGIs) in the hepatocytes. Two groups were identified, depending on whether GGIs
      proliferated or regressed, which was, in turn, found contingent on the duration
      of cyanamide treatment and the drug-free period. Group 1 included 14 cases in
      which GGIs either emerged only in the second biopsy specimen or else were
      increased in the second specimen as compared in the initial specimen. Group 2
      composed of 15 cases in which GGIs were either not observed in either specimen or
      decreased in the second specimen as compared in the initial specimen. Acidophilic
      bodies were sequentially increased in five cases (36%) of group 1 and in none of
      group 2. The severity of portal inflammation worsened in 10 cases (71%) of group
      1 but in 2 cases (13%) of group 2, although the changes in fibrotic process did
      not differ between two groups. These differences could not be explained on the
      basis of the daily ethanol consumption and the length of relapses of the two
      groups. Thus, when cyanamide-treated alcoholics relapsed, the combined effect of
      cyanamide and alcohol produced the development of acidophilic bodies and portal
      inflammation along with the emergence of GGIs.

PMID- 8561307
TI  - Ethanol inhibition of AMPA and kainate receptor-mediated depolarizations of
      hippocampal area CA1.
AB  - Longitudinal hippocampal slices were prepared from adult female rats. The
      excitatory amino acids, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      (AMPA) and kainic acid, were applied to area CA1, and the resulting
      depolarizations were measured using the grease-gap electrophysiological
      technique. Agonist dose-response curves were generated in the presence and
      absence of various concentrations of ethanol. Ethanol (25-200 mM) significantly
      attenuated the depolarizations that were produced by each agonist. In addition,
      we found that ethanol potently antagonized kainate-induced depolarizations across
      the agonist concentration-response curve, whereas it significantly suppressed
      only AMPA responses that were induced with moderate-to-high agonist
      concentrations. These results indicate that ethanol has potent antagonist actions
      against non-N-methyl-D-aspartate (NMDA) excitatory amino acid-induced neuronal
      depolarizations in hippocampal area CA1. Moreover, the relative potency of
      ethanol depends on the specific excitatory agonist tested and the concentration
      of that agonist. This suggests that, in addition to the known effects of ethanol
      on NMDA receptor-mediated activity, it may also potently attenuate ongoing "fast"
      glutamatergic synaptic activity in the hippocampus.

PMID- 8561308
TI  - Gene expression of A- and B-type natriuretic peptides in response to acute
      ethanol ingestion.
AB  - Given that ethanol ingestion is associated with a disruption of water and
      electrolyte balance in addition to being a significant risk factor for
      cardiovascular disease, we have investigated the gene expression of ANP and BNP
      in response to acute doses of ethanol. Wistar rats were administered either a 5
      g/kg dose of ethanol or an equivalent volume of water, and atrial and ventricular
      tissue samples were removed at 30, 60, and 120 min for analyses. Although no
      differences in ANP mRNA were observed between ethanol and water-treated rats
      during the time course, BNP mRNA levels in ethanol-treated rats were 43% of those
      present in water-treated animals in atrial tissue at 120 min. In ventricular
      tissue, BNP mRNA levels were reduced similarly to 38% of control. These results
      suggest a possible differential regulation of A- and B-type natriuretic peptides
      under the influence of ethanol ingestion.

PMID- 8561309
TI  - Permanent neuronal cell loss in the inferior olive of adult rats exposed to
      alcohol during the brain growth spurt: a stereological investigation.
AB  - The purpose of this study was to examine whether exposure of rat pups to alcohol
      postnatally over a period of brain development similar to that of the human 3rd
      trimester results in a permanent loss of cells in the inferior olivary nucleus.
      It was hypothesized that a deficit of neurons in the inferior olive, the sole
      source of climbing fibers, may contribute to the cerebellar dysfunction observed
      following exposure to alcohol during development. Sprague-Dawley rat pups were
      artificially reared and administered alcohol over postnatal days 4-9. One
      artificially reared group received a daily alcohol dose of 4.5 g/kg, administered
      as a 10.2% solution in 2 of 12 daily feedings (10.2% group). This pattern of
      alcohol administration resulted in high peak blood alcohol concentrations with
      near total clearance. The other artificially reared group was fed a diet made
      isocaloric to the alcohol-containing diet (gastrostomy control group). Pups were
      allowed to grow to adulthood and killed on postnatal day 115. The total number of
      neurons in the inferior olivary nucleus was estimated using unbiased
      stereological methods. Exposure to alcohol resulted in a significant deficit in
      the number of neurons in the inferior olive at 115 days of age. The total number
      of neurons in the alcohol-exposed group was 40.12 +/- 8.7 x 10(3), compared with
      53.37 +/- 3.7 x 10(3) in the artificially reared controls. These results indicate
      that there is a permanent deficit of neurons in the inferior olive after
      postnatal exposure to alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8561310
TI  - Effect of ethanol consumption on adult rat liver mitochondrial populations
      analyzed by flow cytometry.
AB  - In the present study, the effects of administering ethanol to adult male rats on
      the distribution of the low fluorescence population (LFP) and high fluorescence
      population (HFP), and the rhodamine-123 fluorescence intensity of these groups of
      mitochondria are analyzed by flow cytometry. Our results show that ethanol
      administration to adult male rats induces a redistribution of the HFP and LFP
      mitochondrial populations leading to an increase of the less functional HFP
      mitochondria. In addition, ethanol induced an increase in the mean intensity of
      green fluorescence of the HFP that is probably related to an increased number of
      rhodamine-123 binding sites per mitochondria resulting from mitochondria
      enlargement.

PMID- 8561311
TI  - Effects of chronic alcohol consumption and aging on dopamine D1 receptors in
      Fischer 344 rats.
AB  - The present study examined the hypothesis that chronic alcoholism augments the
      age-related loss of dopamine D1 receptors. This hypothesis was investigated
      because previous studies reported that both aging and chronic alcoholism produce
      significant changes in dopaminergic systems, and because chronic alcoholism
      potentiates some age-related CNS losses. In addition, this study investigated the
      effects of aging on D1 receptors in animals 1 and 7 days after withdrawal from
      chronic ethanol. Quantitative autoradiography was used to measure [3H]SCH 23390
      binding to D1 receptors in brain areas associated with both the nigrostriatal and
      mesocorticolimbic dopamine systems. Receptors were assessed in 5-, 14-, and 24
      month-old male Fischer 344 rats that were pair-fed a control or 6.6% (v/v)
      ethanol-containing liquid diet for 6 weeks. The results of these studies
      demonstrated that aging is associated with a significant decline in D1 receptors
      in the rostral and caudal striatum, and substantia nigra of both control and
      ethanol-fed rats. These receptor changes in the nigrostriatal system may be
      associated with motor abnormalities. In addition, there was an age-related
      decline in D1 receptors in two brain areas of the mesocorticolimbic system: the
      nucleus accumbens and frontal cortex. The latter findings may be important
      because of the involvement of this system with the rewarding properties of
      ethanol and other drugs of abuse. There were no age-related differences in the
      response of D1 receptors to ethanol withdrawal in the caudal and rostral
      striatum, substantia nigra, and nucleus accumbens.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8561312
TI  - GABAA receptor function and binding in stably transfected cells: chronic ethanol
      treatment.
AB  - Effects of chronic ethanol exposure on GABAA receptors may contribute to
      tolerance and dependence to alcohol. Ethanol treatment of mice and rats can
      produce alterations of GABAA receptor binding, function, and subunit mRNA and
      protein levels. We treated a cell line (PA3 cells) that stably expresses GABAA
      receptors chronically with ethanol. Expression of bovine alpha 1, beta 1, and
      gamma 2L GABAA receptor subunits genes in these cells is controlled by a
      dexamethasone-sensitive promoter, and this provides an excellent system to study
      the regulation by chronic ethanol treatment of receptors with a defined subunit
      composition. The actions of the GABA agonist muscimol on receptor function (36Cl-
      uptake) were not affected by 100 mM ethanol treatment for 4 days, but the actions
      of flunitrazepam (1 microM) were decreased in cells treated with ethanol. The
      functional coupling between benzodiazepine and GABA sites on the receptors was
      affected by chronic ethanol treatment in a manner consistent with results from
      mice. Ethanol treatments (50 or 100 mM) for 4 days did not affect the affinity
      (Kd) or receptor density (Bmax) of [3H]flunitrazepam binding, or the levels of
      alpha 1 subunit mRNA, or alpha 1 or beta 1 subunit proteins. These results
      demonstrate that the regulation of the stably expressed GABAA receptors by
      chronic ethanol, in the absence of neuronal receptor gene promoters, is
      posttranscriptional and likely posttranslational.

PMID- 8561313
TI  - In vitro comparison of the effects of ethanol and acetaldehyde on dorsal root
      ganglion neurons.
AB  - Results of previous experiments designed to investigate the role of acetaldehyde,
      the primary metabolite of ethanol, have been contradictory. Experiments have
      provided evidence that supports and refutes the idea that acetaldehyde is
      responsible for the teratogenic effects observed in fetal alcohol syndrome. In
      the present study, cell culture techniques were used to examine the effects of
      acetaldehyde, both independently and in conjunction with ethanol. The purpose was
      to determine whether acetaldehyde had any effect on survival and process
      outgrowth of dorsal root ganglion (DRG) neurons cultured in vitro. This study
      revealed that acetaldehyde was as toxic to DRG survival as is ethanol, but had a
      lesser effect on neurite outgrowth than ethanol. Also, acetaldehyde and ethanol
      do not act synergistically to damage neurons in culture. The results indicate
      that, although acetaldehyde is probably not solely responsible for ethanol
      neurotoxicity, it does exhibit a secondary toxicity that could be the subject of
      future studies.

PMID- 8561314
TI  - Perinatal maternal ethanol effects on pregnant mice and on offspring viability
      and growth: influences of exposure time and weaning diet.
AB  - C57BL/6 mice were maintained on liquid diets containing 27.5% ethanol-derived
      calories beginning on gestational day 12. For one group, the liquid diet was
      replaced with laboratory chow on the morning of gestational day 18, approximately
      24 hr before delivery. For a second group, the diet was continued for 7 days
      postnatally. Two additional groups were pair-fed isocaloric sucrose diets, and a
      final group was maintained on normal laboratory chow. The mice consumed
      sufficient amounts of diet to provide near 30 g ethanol/kg/day during pregnancy
      and slightly greater amounts during the first postpartum week. The ethanol diet
      produced no maternal deaths and did not alter weight gain during gestational days
      12-17 of pregnancy. The results confirmed previous reports that dietary ethanol
      exposure under conditions that have rather minor effects on the pregnant mouse
      can substantially affect the fetus. As previously reported, when exposure was
      terminated 24 hr before delivery, neonatal mortality was elevated by
      approximately 30%, but birth weight was not altered. When the diet was extended
      into the lactation period, mortality was delayed but not reduced, possibly by
      reducing the severity of ethanol withdrawal. Birthweight was reduced by 10% when
      exposure continued until birth, suggesting that low birthweights for fetal
      ethanol-exposed (FEE) mice can be eliminated by terminating exposure
      approximately 24 hr before delivery. As in previous reports, FEE mice with normal
      birthweights had an attenuated preadolescent growth spurt, suggesting that low
      birthweights and attenuated postnatal growth are likely mediated by different
      mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8561315
TI  - Effect of pre- or postnatal exposure to ethanol on the total number of neurons in
      the principal sensory nucleus of the trigeminal nerve: cell proliferation and
      neuronal death.
AB  - Early exposure to ethanol reduces the number of neurons in many CNS structures in
      vivo. The present study determined whether such reductions are caused by the
      death of neurons. Three groups of ethanol-treated rats were prepared: those
      exposed to ethanol from gestational day (G) 11 to G19 (during the period of
      neuronal generation and migration), from postnatal day (P) 4 to P12 (during the
      period of synaptogenesis), or from P31 to P39 [after the mature structure and
      function of neurons in the principal sensory nucleus (PSN) of the trigeminal
      nerve was established]. During these times, pregnant dams or pups were fed a
      liquid ethanol-containing diet that produced peak blood ethanol concentrations of
      137-157 mg/dl. The number of PSN neurons in mature rats exposed to ethanol pre-
      or postnatally was determined using stereological procedures. The number of PSN
      neurons was also calculated for rats pair-fed an isocaloric liquid control diet
      or fed chow and water and libitum. The volume of the PSN was not affected by pre-
      or postnatal ethanol exposure. The number of PSN neurons, however, was
      significantly affected by ethanol exposure in a time-dependent manner. Prenatal
      exposure lead to a 27.1% decrease in neuronal number. Early postnatal exposure
      led to a smaller decrease (-15.1%), and late postnatal exposure had no affect on
      the number of PSN neurons. These data show not only that ethanol directly
      depresses the proliferation of neuronal precursors, but also that ethanol causes
      the death of neurons during the period of synaptogenesis.

PMID- 8561316
TI  - Alcohol and endotoxin: another path to alcoholic liver injury?

PMID- 8561317
TI  - Oral clonidine premedication reduces postoperative pain in children.
AB  - Clonidine is an effective preanesthetic medication in children, providing a
      preoperative sedative effect. The analgesic properties of the drug have been well
      documented in adults. The current study was designed to investigate the effect of
      oral clonidine given preoperatively on postoperative pain in children undergoing
      minor surgery. In a prospective, randomized, controlled clinical trial, 90
      children aged 5-12 yr undergoing elective ophthalmic, urologic, and otologic
      surgery received placebo (control), clonidine 2 micrograms/kg, or clonidine 4
      micrograms/kg. These drugs were administered 105 min before the estimated time of
      induction of anesthesia and followed by treatment with oral atropine 0.03 mg/kg
      60 min before anesthesia. Anesthesia was induced and maintained with halothane
      and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded
      observer using an objective pain scale (OPS). Clonidine 4 micrograms/kg provided
      lower OPS (highest) scores during 12 h after surgery and reduced requirement for
      postoperative supplementary analgesic (diclofenac suppository) compared with the
      other two regimens. These data suggest that oral clonidine premedication (4
      micrograms/kg) is a possible approach to facilitating postoperative analgesia in
      children undergoing minor surgery.

PMID- 8561318
TI  - Bupivacaine plasma concentrations during continuous epidural anesthesia in
      infants and children.
AB  - Venous bupivacaine plasma concentrations were measured in six neonates and
      infants aged 4 days to 3.9 mo (mean, 2.1 mo) and 10 infants and children aged 9
      mo to 6 yr (mean, 3.1 yr) after administration of an initial bolus of 0.5 mL/kg
      bupivacaine 0.25%, followed by a continuous infusion of local anesthetic (0.25
      mL.kg-1.h-1) over a period of 4 h (first hour: bupivacaine 0.25%, then reduced to
      0.125%). Plasma concentrations of local anesthetic measured at 180 min and 300
      min after beginning of bupivacaine administration were significantly higher in
      younger infants when compared to older infants and children (180 min: 0.67 +/-
      0.24 micrograms/mL [0.25-0.97] vs 0.27 +/- 0.11 micrograms/mL [0.19-0.55], P <
      0.01; 300 min: 0.86 +/- 0.36 micrograms/mL [0.35-1.25] vs 0.34 +/- 0.12
      micrograms/mL [0.18-0.57], P < 0.01). The results of our study show that despite
      applying the same dosage of epidural bupivacaine significantly higher plasma
      concentrations were seen after short periods of continuous infusion in infants up
      to 4 mo than in children older than 9 mo.

PMID- 8561319
TI  - Perioperative plasma concentrations of endothelin and natriuretic peptides in
      children undergoing living-related liver transplantation.
AB  - To investigate the clinical significance of endothelin (ET), natriuretic
      peptides, and the renin-angiotensin-aldosterone system in pediatric liver
      transplantation, we measured plasma levels of ET, atrial and brain natriuretic
      peptides (ANP, BNP), aldosterone, and plasma renin activity in 18 patients (aged
      0.5-12 yr; median 1 yr) undergoing living-related liver transplantation due to
      congenital biliary atresia and severe liver cirrhosis. Before transplantation,
      the plasma ET level (28.9 +/- 2.5 [mean +/- SEM] pg/mL) was increased compared
      with that of healthy children (10-18 pg/mL), but decreased during the anhepatic
      phase (22.5 +/- 1.6 pg/mL). It increased again after reperfusion and remained at
      high levels in the early postoperative period (postoperative day 3, 27.8 +/- 3.0
      pg/mL). Plasma levels of ANP and BNP and aldosterone and plasma renin activity
      were also high before surgery. Plasma ANP and BNP did not change significantly
      during surgery. After transplantation, plasma BNP significantly increased, and
      plasma ANP tended to increase. Plasma aldosterone increased markedly during the
      anhepatic phase, although plasma renin activity decreased. After transplantation,
      plasma aldosterone and plasma renin activity both decreased to within normal
      levels. Mean arterial blood pressure increased gradually after reperfusion and
      surgery (postoperative day 3, 35.7 +/- 5.2% increase). No substantial differences
      in these variables occurred between the younger (< or = 1.0 yr, n = 9) and older
      patients (> 1.0 yr, n = 9). These results suggest that ET production in the
      cirrhotic liver is augmented and ET, natriuretic peptides, and the renin
      angiotensin-aldosterone system all play some role in the circulatory regulation
      during perioperative periods of pediatric liver transplantation.

PMID- 8561320
TI  - Hemodynamic effects of amrinone in children after Fontan surgery.
AB  - After Fontan repair in children, we performed a prospective, open-label study to
      evaluate the effect of amrinone on pulmonary vascular resistance (PVRI). Eight
      patients who underwent the Fontan repair had baseline arterial pressure, left
      atrial pressure, central venous pressure, and cardiac output measured
      postoperatively. Hemodynamic measurements were repeated after amrinone 4.5 mg/kg.
      The PVRI tended to decrease, but the change was not statistically significant.
      Although the systemic vascular resistance decreased to 802 +/- 222 from 941 +/-
      191 dynes.s.cm-5.m-2 (P < 0.05), mean arterial blood pressure was unchanged.
      Cardiac index (3.8 +/- 1.2 to 4.7 +/- 1.6 L.min-1.m-2) and stroke volume index
      (23.6 +/- 6.7 to 30.5 +/- 8.1 mL.beat-1.m-2) increased, and heart rate decreased
      (160 +/- 21 to 151 +/- 24 bpm) (P < 0.05). Colloid transfusion during amrinone
      bolus administration was 13.9 mL/kg. The mean serum amrinone concentration was
      4.2 micrograms/mL at the end of bolus and clearance was 2.24 mL.kg-1.min-1.
      Arrhythmias and thrombocytopenia were not noted. We conclude that amrinone
      administration is effective in increasing cardiac output in children who have
      undergone a Fontan repair.

PMID- 8561321
TI  - Relationship between end-tidal and arterial carbon dioxide with laryngeal mask
      airways and endotracheal tubes in children.
AB  - The laryngeal mask airway (LMA) is a useful tool for securing the airway in
      adults and children and may be substituted for an endotracheal tube (ETT) in
      selected patients undergoing general anesthesia. The correlation between end
      tidal and arterial carbon dioxide during controlled ventilation via LMA has not
      been reported in a within-patient design in pediatric patients. After induction
      of general anesthesia, 22 children had a LMA placed and mechanical ventilation
      initiated. After reaching steady-state end-tidal carbon dioxide (PETCO2), an
      arterial blood sample was obtained and the partial pressure of carbon dioxide
      (PaCO2) was measured. The LMA was then removed, the trachea was intubated, and
      identical ventilatory variables were resumed. After a stable PETCO2 was
      reestablished (minimum 5 min), a second PaCO2 was measured and the PETCO2
      recorded. The mean PETCO2 and PaCO2 obtained during ventilation via the LMA were
      37.7 +/- 3.31 and 41.9 +/- 9.09, respectively. The mean PETCO2 and PaCO2 obtained
      during ventilation via the ETT were 35.2 +/- 2.86 and 39.2 +/- 5.25,
      respectively. Analysis of differences between PaCO2 and PETCO2 revealed a bias +/
      precision of 4.0 +/- 3.42 and 4.2 +/- 3.66 with ventilation via ETT and LMA,
      respectively. The root mean square error was 0.85 for the ETT and 0.89 for the
      LMA. Our results indicate that in infants and children weighing more than 10 kg
      who are mechanically ventilated via the LMA PETCO2 is as accurate an indicator of
      PaCO2 as when ventilated via ETT.

PMID- 8561322
TI  - Displacement of the endotracheal tube caused by change of head position in
      pediatric anesthesia: evaluation by fiberoptic bronchoscopy.
AB  - Displacement of the endotracheal tube (ETT) caused by flexion and extension of
      the neck and the placement of a tongue depressor was investigated in 10 small
      children between the ages of 16 and 19 mo by means of a fiberoptic bronchoscope.
      The ETT tip moved a mean distance of 0.9 cm toward the carina with flexion and
      1.7 cm toward the vocal cords with extension of the neck. After the placement of
      a tongue depressor, the ETT tip, which had once moved toward the vocal cords with
      neck extension, was displaced a mean distance of 1.2 cm toward the carina. Our
      results demonstrate that endobronchial intubation and accidental extubation could
      occur after significant changes of the head position and careless placement of a
      tongue depressor in small children.

PMID- 8561323
TI  - Continuous hypopharyngeal pH measurements in spontaneously breathing anesthetized
      outpatients: laryngeal mask airway versus tracheal intubation.
AB  - We measured the hypopharyngeal pH to compare the incidence of regurgitation
      associated with the laryngeal mask airway (LMA) and the tracheal tube (TT) in
      spontaneously breathing, anesthetized patients. Sixty outpatients scheduled for
      elective peripheral surgery with a standardized general anesthetic technique were
      randomly allocated to receive either a LMA (n = 28) or a TT (n = 32) for airway
      management. A 4-mm pH electrode was placed in the hypopharynx, and pH values were
      continuously collected and stored in a portable pH data logger system until the
      end of the operation. There were no episodes of hypopharyngeal regurgitation (pH
      < 4) detected during the course of measurement. At no time did the hypopharyngeal
      pH value decrease below 5.5. The hypopharyngeal pH values in both groups were
      similar, ranging between 5.5 and 7.5, with median values of 5.7 and 6.2 in the
      LMA and TT groups, respectively. The pH in any given patient did not vary more
      than 1.0 unit from the initial value recorded at the start of the operation. We
      conclude that continuous monitoring of the hypopharyngeal pH in spontaneously
      breathing, anesthetized outpatients failed to detect evidence of pharyngeal
      regurgitation.

PMID- 8561324
TI  - Postoperative alpha 2-adrenergic stimulation attenuates protein catabolism.
AB  - The metabolic effects of continuous intravenous (IV) application of the alpha 2
      agonist clonidine were evaluated by assessment of nitrogen economy and
      postaggression endocrine patterns. Twenty-four patients undergoing
      abdominothoracic esophageal cancer resection were studied. Thirteen of these
      patients with alcohol abuse were treated postoperatively with IV clonidine for
      prevention of alcohol withdrawal syndrome. Eleven patients who were not treated
      with clonidine served as controls. All patients were treated in a standardized
      manner in regard to surgical technique, balanced anesthesia, and postoperative
      intensive care treatment, including thoracic epidural analgesia with bupivacaine
      and fentanyl. Isonitrogenous and isocaloric nutrition was comparable in all
      patients. A significantly improved cumulated 6-day nitrogen balance was found in
      clonidine-treated patients (-1.5 +/- 4.9 g nitrogen) compared to the control
      group (-17.6 +/- 4.2 g nitrogen) (P < 0.05). The main reason for improved
      nitrogen economy may be clonidine-induced growth hormone (GH) release. The
      pattern of insulin-like growth factor I (IGF-I) and insulin-like growth factor
      binding protein 3 (IGFBP-3) concentrations could support this hypothesis.

PMID- 8561325
TI  - The effects of N-methyl-D-aspartate agonists and antagonists on isolated bovine
      cerebral arteries.
AB  - This pharmacologic study examines the direct cerebrovascular effects of N-methyl
      D-aspartate (NMDA) receptor agonists and antagonists to determine whether large
      cerebral arteries have NMDA receptors. Bovine middle cerebral arteries were cut
      into rings to measure isometric tension development in vitro. Two competitive
      agonists, L-glutamate and NMDA, each had negligible effects on ring tension in
      the absence of exogenous vasoconstrictors. L-glutamate (in high concentrations)
      produced direct relaxation of potassium (K+)-constricted arteries, but the
      relaxation was not selective for L-glutamate, D-glutamate, or mannitol.
      Relaxation with L-glutamate was abolished when it was isosmotically substituted
      in the K(+)-rich medium. NMDA (in the absence or presence of glycine) and two
      competitive antagonists, 2-amino-5-phosphopentanoic acid (AP5) and (+/-)-3-(s
      carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), each had little effect on
      the tone of arteries preconstricted with potassium or the stable thromboxane A2
      analog U-46,619. Three noncompetitive antagonists (S(+)-ketamine, dizocilpine,
      and dextrorphan) and their steroeisomers (R(-)-ketamine, (-)MK-801, and
      levorphanol) each produced dose-dependent relaxation of K(+)- or U-46,619
      constricted arteries; relaxation was not selective for the (+) or (-)
      stereoisomers. These results suggest that large cerebral arteries lack NMDA
      receptors mediating constriction or relaxation. All noncompetitive antagonists
      dilated cerebral arteries, but by mechanisms that were not stereospecific.

PMID- 8561326
TI  - Validation in volunteers of a near-infrared spectroscope for monitoring brain
      oxygenation in vivo.
AB  - Cerebral oximeters based on near-infrared spectroscopy may provide a continuous,
      noninvasive assessment of cerebral oxygenation. We evaluated a prototype cerebral
      oximeter (Invos 3100; Somanetics, Troy, MI) in 22 conscious, healthy volunteers
      breathing hypoxic gas mixtures. Using the first 12 subjects (training group), we
      developed an algorithm based on the mathematic relationship that converts
      detected light from the field surveyed by the probe to cerebral hemoglobin oxygen
      saturation (CSfO2). To develop the algorithm, we correlated the oximeter result
      with the estimated combined brain hemoglobin oxygen saturation (CScombO2, where
      CScombO2 = SaO2 x 0.25 + SjO2 x 0.75 and SjO2 = jugular venous saturation). We
      then validated the algorithm in the remaining 10 volunteers (validation group). A
      close association (r2 = 0.798-0.987 for individuals in the training group and r2
      = 0.794-0.992 for individuals in the validation group) existed between CSfO2 and
      CScombO2. We conclude that continuous monitoring with cerebral oximetry may
      accurately recognize decreasing cerebral hemoglobin oxygen saturation produced by
      systemic hypoxemia.

PMID- 8561327
TI  - The influence of carbon dioxide and body position on near-infrared spectroscopic
      assessment of cerebral hemoglobin oxygen saturation.
AB  - Near-infrared spectroscopy may allow continuous and noninvasive monitoring of
      regional brain hemoglobin oxygen saturation by measuring the differential
      absorption of infrared light by oxyhemoglobin and deoxyhemoglobin. We have
      previously examined the correlation between the spectroscopic signal generated by
      a prototype cerebral oximeter (Invos 3100; Somanetics, Troy, MI), and global
      brain hemoglobin oxygen saturation calculated from arterial and jugular venous
      bulb oxygen saturations. Because the technology does not distinguish between
      arterial and venous hemoglobin saturation, changes in the proportion of cerebral
      arterial and venous blood volume, which may result from changes in blood flow or
      venous distending pressure, may confound measurements. In eight conscious
      volunteers breathing hypoxic oxygen mixtures, we examined the influence of
      supine, 20 degrees Trendelenburg, and 20 degrees reverse Trendelenburg positions
      on the correlation of the spectroscopic measurement of cerebral oxygen saturation
      in the field assessed by the probe (CSfO2) and the calculated brain hemoglobin
      oxygen saturation (CScombO2), estimated as 0.25 x arterial saturation plus 0.75 x
      jugular venous bulb oxygen saturation. We found that changes in position did not
      influence the association between CSfO2 and CScombO2 (r2 = 0.69-0.885) during
      hypoxic challenge. In a second set of eight volunteers, we studied the influence
      of hypercapnia and hypocapnia and body position on the association between CSfO2
      and CScombO2, and found that they were less well correlated (r2 = 0.366-0.976) in
      individual patients. Because changes in body position and Paco2 confound the
      relationship between CSfO2 and CScombO2, changes in CSfO2 can best be assessed if
      position and Paco2 are constant.

PMID- 8561328
TI  - Pregnancy and ephedrine increase the release of nitric oxide in ovine uterine
      arteries.
AB  - Ephedrine is the preferred vasoconstrictor for the treatment of hypotension after
      epidural and spinal anesthesia in obstetrics because it preserves uterine
      perfusion better than pure alpha-adrenergic agonists. Previous studies of uterine
      vascular rings in vitro suggested that direct uterine vasoconstriction from
      ephedrine is reduced during pregnancy. This study examined the hypothesis that
      nitric oxide synthase (NOS) is up-regulated in uterine arteries during pregnancy,
      and that ephedrine stimulates NOS to release nitric oxide (NO) and diminish
      direct vasoconstriction. Uterine arterial vessels were obtained from 12 pregnant
      and 9 nonpregnant ewes, and vessel tension was monitored in vitro in response to
      escalating concentrations of ephedrine or metaraminol. In some experiments,
      vascular endothelium was mechanically removed, while in others antagonists of NO
      synthesis (N omega-nitro-L-arginine methyl ester [L-NAME], NO diffusion
      (hemoglobin [Hgb]), or guanylate cyclase (methylene blue [MB]) were included. In
      other experiments, solutions containing ephedrine were superfused over uterine
      arteries from pregnant ewes onto uterine arteries from nonpregnant ewes. Finally,
      NOS activity, determined by 14C-citrulline generation, was determined in uterine
      arteries from pregnant and nonpregnant ewes. Both ephedrine and metaraminol
      caused concentration-dependent constriction of uterine arterial rings from
      pregnant and nonpregnant animals. Pregnancy reduced maximum constriction from
      ephedrine more than metaraminol. Similarly, ephedrine-induced constriction was
      increased more than that of metaraminol in uterine arteries from pregnant animals
      treated to diminish the effects of nitric oxide (L-NAME, Hgb, MB, endothelium
      removal). Ephedrine's constriction of uterine arteries from nonpregnant animals
      was reduced when it was superfused over uterine arteries from pregnant animals.
      NOS activity was increased in uterine arteries from pregnant compared to
      nonpregnant animals. These studies confirm decreased direct uterine arterial
      vasoconstriction during pregnancy from ephedrine and support the hypothesis of
      increased release of an endogenous vasodilator (NO), either from the vascular
      endothelium or the vessel wall, as the cause for this decreased vasoconstriction.

PMID- 8561329
TI  - Epinephrine-induced tachycardia is different from contraction-associated
      tachycardia in laboring patients.
AB  - Maternal tachycardic responses to the intravenous injection of epinephrine 15
      micrograms were compared with tachycardic responses induced by the pain of labor
      in a double-blind, prospective study of 15 women in active labor. After placement
      of an epidural catheter, maternal heart rate was continuously recorded. Each
      patient received, in uterine diastole, two injections of a test dose (epinephrine
      15 micrograms + lidocaine 45 mg) at 2-4 min intervals, once via the epidural
      catheter and once intravenously in a random fashion. From the maternal heart rate
      strips, the acceleratory phase (bpm) of epinephrine-induced tachycardic responses
      (EITRs) and contraction-associated tachycardic responses (CATRs) were calculated.
      The upper bound of the 99% confidence interval (CI) to discriminate between the
      two groups was estimated. The acceleratory phase of EITRs was 1.85 +/- 0.61 bpm.
      The acceleratory phase of CATRs was 0.69 +/- 0.49 (P < 0.0003). The upper bound
      of the 99% CI was 1.17 bpm. Using this value to discriminate between EITRs and
      CATRs, all EITRs would be correctly identified. We conclude that on-line analysis
      of maternal tachycardic responses might be used in laboring women to discriminate
      between EITRs and CATRs and further improve the accuracy of an epinephrine test
      dose during the performance of epidural analgesia.

PMID- 8561330
TI  - The effects of needle type, gauge, and tip bend on spinal needle deflection.
AB  - Although the use of fine-gauge spinal needles reduces the incidence of postdural
      puncture headache, they are associated with increased risk of placement failure
      as a result of deflection and bending. This in vitro study quantifies spinal
      needle deflection from the axis of insertion with respect to needle type, gauge,
      and tip bend. In addition to straight-tip needles, those with standardized 5
      degrees and 10 degrees tip bends were studied. The purpose was to examine the
      effect of tip bend, which has been described with small gauge spinal needles
      after bony contact, on needle path deflection. Needles studied included Quincke
      (Q), Sprotte (S), and Whitacre (W) in sizes ranging from 18-gauge to 29-gauge.
      Needles were inserted perpendicularly into porcine paraspinous muscle followed by
      radiologic investigation. Measurements of needle deflection from the axis of
      insertion at depths of 20, 40, and 60 mm were performed in a blinded fashion.
      Straight-tip Q needle deflection, but not W or S, was correlated with gauge and
      depth of insertion. Although there were differences within needle type groups,
      needle deflection was generally correlated with the degree of tip bend. We
      conclude that spinal needle deflection is dependent on the type of needle (W < S
      < Q), and that the magnitude of deflection is related to gauge (large < small)
      and tip bend (straight < 5 degrees < 10 degrees).

PMID- 8561331
TI  - Repeated dural punctures increase the incidence of postdural puncture headache.
AB  - Previous studies have failed to find a significant correlation between the number
      of dural punctures and the incidence of postdural puncture headache (PDPH),
      questioning the hypothesis that leakage of cerebrospinal fluid (CSF) through the
      dural tear is the cause of PDPH. We hypothesized that insufficient statistical
      power of these studies was the cause for this unexpected finding, and re-examined
      whether repeated dural punctures increase the incidence of PDPH by analyzing
      prospectively collected data on 8034 spinal anesthetics. Uneventful spinal
      anesthetics, including a single subarachnoid injection of local anesthetics,
      occurred in 7865 (97.9%) cases, whereas failed spinal anesthetics requiring
      repeated dural puncture for a second subarachnoid injection of local anesthetics
      occurred in 165 (2.1%) cases. The two groups were similar with regard to age,
      sex, and ASA physical status. We found that repeated dural punctures
      significantly increased the incidence of PDPH. We conclude that increased risk of
      PDPH is a disadvantage of performing a second subarachnoid injection of local
      anesthetics after a failed spinal anesthetic. Moreover, this result suggests that
      leakage of CSF through the dural tear is the most plausible cause of PDPH.

PMID- 8561332
TI  - The effects of epidural anesthesia on ventilatory response to hypercapnia and
      hypoxia in elderly patients.
AB  - Epidural anesthesia may impair pulmonary ventilation in elderly people. We
      examined the effects of lumbar or thoracic epidural anesthesia on resting
      ventilation, arterial blood gas tensions, the ventilatory response to
      hypercapnia, and progressive isocapnic hypoxia in elderly patients. Two groups of
      eight unpremedicated elderly patients, aged 65 yr or older, undergoing lower or
      upper abdominal surgery, respectively, were studied twice before and 20 min after
      the lumbar or thoracic administration of 10 mL of 2% lidocaine. Lumbar epidural
      anesthesia had no significant effect on resting ventilation, whereas thoracic
      epidural caused a significant 13% decrease in minute ventilation and a 14%
      decrease in tidal volume (P < 0.05). The ventilatory response to hypercapnia was
      significantly increased after lumbar epidural anesthesia, but no change was
      observed after thoracic epidural anesthesia. The slope of the hypoxic response
      curve did not show any change in either group, but minute ventilation at a Spo2
      of 90% significantly increased after lumbar epidural anesthesia (P < 0.05). We
      conclude that neither lumbar nor thoracic epidural anesthesia per se impairs the
      ventilatory response to hypercapnia and hypoxia, despite slight impairment in
      resting ventilation by thoracic epidural anesthesia, in elderly patients.

PMID- 8561333
TI  - Hemodynamic effects of spinal anesthesia in the elderly: single dose versus
      titration through a catheter.
AB  - Sixty elderly patients (> 70 yr old) undergoing surgery for hip fracture were
      prospectively studied in order to compare hemodynamic tolerance of titrated doses
      of hyperbaric bupivacaine using continuous spinal anesthesia (CSA) versus single
      dose spinal anesthesia (SDSA). Patients were randomized into two groups (CSA
      group: n = 30; SDSA group: n = 30). The SDSA patients received 10-15 mg of 0.5%
      hyperbaric bupivacaine (based on age and height), and the CSA patients received a
      starting dose of 5 mg of 0.5% hyperbaric bupivacaine, followed after 15 min by
      optional reinjection of 2.5 mg every 5 min until a T10 level sensory block was
      reached. Onset of anesthesia, noninvasive hemodynamic variables and the need for
      ephedrine were studied for 4 h after induction of anesthesia. Spinal anesthesia
      was successful in all patients. Decreases in mean arterial pressure were
      significantly less frequent and less pronounced in the CSA group (19.9% +/- 1.6%
      of the baseline value) than in the SDSA group (40.2% +/- 1.9%, P < 0.0001). The
      mean dose of ephedrine was significantly less in the CSA group (1.8 +/- 0.7 mg,
      administered to only 37% of patients) than in the SDSA group (19.4 +/- 3.3 mg
      administered to all patients, P < 0.0001). No late complications related to the
      spinal anesthesia technique were observed in either group. We concluded that CSA,
      using small titrated doses of 0.5% hyperbaric bupivacaine, is safe, efficient,
      and provides better hemodynamic stability than SDSA in elderly patients.

PMID- 8561334
TI  - Compound motor action potential recording distinguishes differential onset of
      motor block of the obturator nerve in response to etidocaine or bupivacaine.
AB  - The purpose of this investigation was to establish an objective (quantitative)
      method for determining onset time of motor block induced by different local
      anesthetics. Twenty-four consenting patients undergoing transurethral surgery
      during spinal anesthesia were randomized to receive direct obturator nerve block
      with 10 mL of plain bupivacaine 0.5% (n = 12) or 10 mL of plain etidocaine 1% (n
      = 12). Another 14 patients (control group) received obturator nerve "block" with
      saline. After identification of the obturator nerve, patients underwent testing
      of nerve conduction by recording compound motor action potentials (CMAPs) of
      thigh adductor muscles in response to stimulation provided by a nerve stimulator
      at 0.2 to 0.5-mA currents. Testing ended when CMAP amplitudes had returned to
      their baseline values (control group) or when motor blockade was 90% complete
      (local anesthetic groups). In all 38 patients, the amplitude of the thigh CMAPs
      decreased immediately after injection of saline or local anesthetic. While CMAP
      amplitudes in the control group returned to their initial (baseline) values after
      3-6 min, the patients receiving etidocaine or bupivacaine achieved > or = 90%
      motor blockade after 6 and 13 min, respectively. In the present report, the time
      to > or = 90% block was significantly faster in patients given etidocaine
      compared with those given bupivacaine. We conclude that electromyographic
      recording of CMAPs can be used to compare the ability of different local
      anesthetics to induce motor block.

PMID- 8561335
TI  - Nonanesthetics can suppress learning.
AB  - Nonanesthetic gases or vapors do not abolish movement in response to noxious
      stimuli despite partial pressures and affinities for lipids that would, according
      to the Meyer-Overton hypothesis, predict such abolition. We investigated whether
      nonanesthetics depress learning and memory (i.e., provide amnesia). To define
      learning, we used a "fear-potentiated startle paradigm": rats trained to
      associate light with a noxious stimulus (footshock) will startle more, as
      measured by an accelerometer, when a startle-eliciting stimulus (e.g., a noise)
      is paired with light than when the startle-eliciting stimulus is presented alone.
      We imposed light-shock pairings on 98 rats under three conditions: no anesthesia
      (control); 0.20, 0.29, and 0.38 times the minimum alveolar anesthetic
      concentration (MAC) of desflurane; or two nonanesthetics (1,2
      dichloroperfluorocyclobutane and perfluoropentane) at partial pressures predicted
      from their lipid solubilities to be between 0.2 and 1 MAC. Desflurane produced a
      dose-related depression of learning with abolition of learning at 0.28 MAC.
      Perfluoropentane at 0.2-predicted MAC had the same effect as 0.28 MAC desflurane.
      1,2-Dichloroperfluorocyclobutane at 0.5- to 1-predicted MAC abolished learning.
      Because nonanesthetics suppress learning but not movement (the two critical
      components of anesthesia), they may prove useful in discriminating between
      mechanisms and sites of action of anesthetics.

PMID- 8561337
TI  - Surgical patients' attitudes regarding participation in clinical anesthesia
      research.
AB  - We designed a questionnaire to identify the factors influencing both day of
      admission surgery (DAS) and ambulatory (AMB) patients in their decision whether
      to participate in and give informed consent for clinical anesthesia research. On
      the day of surgery, 276 patients were approached to complete a questionnaire and
      a visual analog scale (VAS) to assess anxiety. The data collected were
      observational and are presented as percentages for each group (DAS and AMB). One
      hundred eighty-two patient (60 DAS and 122 AMB) completed questionnaires. Both
      DAS and AMB patients desired 20-30 min to read a consent form. Preferred
      conditions for enrollment by both groups were as follows: interview at the time
      of preadmission testing; after consulting with their physician; in a private
      setting while dressed in street clothes; and with assurance that the investigator
      would also participate in the study, if eligible. Unacceptable conditions were as
      follows: research associated with any risk and interview in the operating room
      holding area. All patients responded that they were capable of making the
      decision whether to participate in research on the day of surgery. Most AMB and
      DAS patients found it acceptable to be recruited on the day of surgery, if
      approached appropriately.

PMID- 8561336
TI  - Propofol produces differences in behavior but not chloride channel function
      between selected lines of mice.
AB  - We report differential central nervous system (CNS) sensitivity to propofol
      between Long Sleep (LS) and Short Sleep (SS) mice, selectively bred for their
      differential CNS sensitivity to ethanol. Intravenous propofol requirements for
      loss of righting reflex, or sleep time, were measured to define the extent of
      this sensitivity. LS mice slept approximately two times longer than SS mice at
      equal doses. Awakening plasma and brain levels of the SS line were, respectively,
      two and three times that of the LS line (P < 0.0001). This suggests that the LS
      and SS sleep time difference is CNS mediated, and that propofol and ethanol may
      share common genes that determine anesthetic sensitivities. The ethanol effect
      may be at least partially mediated by gamma-aminobutyric acid-A (GABAA) receptor
      function. Propofol had no differential effect on GABAA receptor function, as
      measured by chloride flux in LS and SS brain microsac preparations. Either the
      GABAA receptor does not mediate propofol sleep time, or qualitative differences
      cannot be demonstrated using 36Cl- uptake in brain membranes.

PMID- 8561338
TI  - Tropisetron for the prevention of postoperative nausea and vomiting in women
      undergoing gynecologic surgery.
AB  - The aim of this study was to evaluate the efficacy of tropisetron, a selective 5
      hydroxytryptamine type 3 (5-HT3) receptor antagonist, versus placebo in the
      prevention of postoperative nausea and vomiting in patients undergoing general
      anesthesia for gynecologic surgery. Ten minutes before induction of general
      anesthesia, 80 patients received in a double-blind manner a single intravenous
      (IV) injection of either 5 mg tropisetron or a matching placebo. Anesthesia was
      induced with thiopental and maintained with nitrous oxide and enflurane in
      oxygen. In the first 24 h postoperatively 7 of 40 patients (17.5%) given
      tropisetron and 16 of 40 patients (40%) receiving placebo vomited (P < 0.05). The
      incidence of nausea was 30% (12/40) in the tropisetron group and 52% (21/40) in
      the placebo group (P < 0.05). A total effective antiemetic response showed 26
      patients (65%) in the tropisetron group and 16 patients (40%) in the placebo
      group (P < 0.05). We conclude that tropisetron given IV prior to gynecologic
      procedures in general anesthesia significantly reduces postoperative nausea and
      vomiting when compared to placebo without causing any adverse effect.

PMID- 8561339
TI  - The effects of sevoflurane, enflurane, and isoflurane on baroreceptor-sympathetic
      reflex in rabbits.
AB  - This study was designed to determine the effects of sevoflurane, enflurane, and
      isoflurane ranging from 0.5 to 1.25 minimum alveolar anesthetic concentration
      (MAC) on spontaneous efferent renal sympathetic nerve activity (RNA) and the
      barorecptor-sympathetic reflex in rabbits. Enflurane produced significant
      decreases in spontaneous RNA by 22.5% +/- 6.6% at 1.0 MAC, while sevoflurane and
      isoflurane, at the equivalent MAC, did not. All of the anesthetics attenuated the
      baroreflex gain similarly when mean blood pressure (MBP) was changed by sodium
      nitroprusside or phenylephrine intravenously. However, the sensitivity of
      baroreceptors at the aortic wall was not changed by any anesthetic, because no
      changes in the relationship between aortic nerve activity and MBP were obtained
      in anesthetic concentration even at 1.25 MAC. Furthermore, these anesthetics
      suppressed the sympathoinhibitory response to aortic nerve stimulation above 1.0
      MAC. In conclusion, enflurane inhibits RNA to a greater degree than sevoflurane
      or isoflurane. However, all three anesthetics depress the reflex regulation of
      RNA to the same degree. The suppression on the baroreceptor-sympathetic reflex
      does not appear to be related to a change in the receptor sensitivity on the
      aorta, but is mediated by suppression of the central or peripheral sympathetic
      integrating system.

PMID- 8561340
TI  - Effect of halothane and isoflurane on in situ diameter responses of small
      mesenteric veins to acute graded hypercapnia.
AB  - The purpose of the present study was to quantify the inhibitory effect of inhaled
      halothane and isoflurane on acute hypercapnia-induced responses of capacitance
      regulating veins and related cardiovascular variables in response to sequential
      40-s periods of 5%, 10%, 15%, and 20% inspired CO2 (FICO2). Measurements were
      made in normoxic alpha-chloralose-anesthetized rabbits before, during, and after
      either 0.75 minimum alveolar anesthetic concentration inhaled halothane or
      isoflurane. The graded hypercapnia caused graded venoconstriction and bradycardia
      but minimal pressor responses. Hypercapnia-induced venoconstriction was blocked
      by prior local superfusion of the exposed veins with 3 x 10(-6) M tetrodotoxin.
      Both the hypercapnia-induced venoconstriction and bradycardia responses were
      significantly attenuated by halothane or isoflurane and did not fully recover
      after removal of the anesthetics from the circulation. Both anesthetics produced
      a significant baseline (i.e., prehypercapnia) hypotension and a tendency toward a
      resultant tachycardia. The baseline hypotension did not recover completely after
      elimination of the anesthetic. Neither anesthetic altered baseline vein diameter.
      These results agree with previous studies demonstrating that hypercapnic acidosis
      produces mesenteric venoconstriction by elevating excitatory sympathetic efferent
      neural input via activation of peripheral and central chemoreceptors and that
      bradycardia results from activation of compensatory baroreflexes. The neural
      components of these reflexes are possible primary sites for attenuation of these
      cardiovascular responses by halothane and isoflurane.

PMID- 8561341
TI  - Intravenous lidocaine does not attenuate the cardiovascular and catecholamine
      response to a rapid increase in desflurane concentration.
AB  - This study was designed to investigate the effect of intravenous lidocaine on the
      sympathetic activity after a rapid increase in desflurane concentration. Twenty
      ASA grade I and II patients, were allocated randomly to a control group (C) and a
      lidocaine group (L). After induction of anesthesia with intravenous propofol 2
      mg/kg and muscle relaxation with intravenous vecuronium 0.1 mg/kg, desflurane was
      given to achieve an end-tidal minimum alveolar anesthetic concentration (MAC) of
      0.7 Group L received 1.5 mg/kg lidocaine intravenously, while Group C received an
      equal volume of 0.9% sodium chloride solution intravenously. These solutions were
      prepared and coded by a colleague who took no further part in the study. The
      concentration of desflurane was then abruptly increased to 1.5 MAC. Heart rate
      and mean arterial pressure were noted every half minute. Blood samples were taken
      for plasma catecholamines at rest, 0.7 MAC, and at 1-min intervals for 5 min
      after the increase in desflurane concentration. There was a significant increase
      in heart rate and mean arterial pressure in both groups. The increase in heart
      rate was significantly less in Group L from 0.5 until 2.5 min (P < 0.05). There
      was no difference in mean arterial pressure between the groups except at 4.5 and
      5.0 min (P < 0.05). Plasma catecholamines were not significantly different
      between the groups. Intravenous lidocaine did not attenuate the sympathetic
      response to a rapid increase in desflurane concentration. It is unlikely that
      airway irritation is the cause of this phenomenon.

PMID- 8561342
TI  - The effects of ketamine on renal sympathetic nerve activity and phrenic nerve
      activity in rabbits (with vagotomy) with and without afferent inputs from
      peripheral receptors.
AB  - One reason for the reported conflicting results of the effect of ketamine on
      hemodynamics and respiration may be variations in afferent inputs from peripheral
      receptors to the central nervous system. In order to evaluate unmasked direct
      effects of ketamine on sympathetic nerve and phrenic nerve outflow, totally
      deafferented (involving vagus, sinus nerve, aortic depressor nerve) rabbits (n =
      18), rabbits with vagotomy (n = 21), and neuraxis-intact rabbits (n = 6) were
      used in this study. The animals were anesthetized with urethane and mechanically
      ventilated. Ketamine 0.5, 1, or 2 mg/kg was injected intravenously and mean
      arterial pressure (MAP), heart rate (HR), and integrated renal sympathetic nerve
      and phrenic nerve activity (IRSNA, IPNA) were recorded before, and 1, 2, 3, 5,
      and 10 min after injection. MAP and IRSNA were significantly decreased, even by
      the smallest dose of ketamine, in the totally deafferented group. IPNA was
      decreased by the largest dose of ketamine only in the totally deafferented group.
      On the other hand, spontaneous respiratory frequency was decreased in the totally
      deafferented and vagotomy groups, but more so in the totally deafferented group.
      In the neuraxis-intact group, the only significant change with the largest dose
      of ketamine, 2 mg/kg was a slight increase in HR. We conclude that ketamine can
      suppress vasomotor and respiratory centers directly, and that the suppression is
      counterbalanced by afferent inputs from peripheral receptors.

PMID- 8561343
TI  - Comparison of end-tidal PCO2 and average alveolar expired PCO2 during positive
      end-expiratory pressure.
AB  - The measurement of average alveolar expired PCO2 (PAECO2) weights each PCO2 value
      on the alveolar plateau of the CO2 expirogram by the simultaneous change in
      exhaled volume. PAECO2 can be determined from a modified analysis of the Fowler
      anatomic dead space (VDANAT). In contrast, end-tidal PCO2 (PETCO2) only measures
      PCO2 in the last small volume of exhalate. In conditions such as mechanical
      ventilation with positive end-expiratory pressure (PEEP), where the alveolar
      plateau can have a significant positive slope, we questioned how much PETCO2
      could overestimate PAECO2. Accordingly, in six anesthetized ventilated dogs, we
      digitally measured and processed tidal PCO2 and flow to determine VDANAT. We
      determined PETCO2 and PAECO before and after the application of 7.6 cm H2O PEEP.
      Alveolar dead space to tidal volume fraction (VD/VT) was determined by [arterial
      PCO2- alveolar PCO2]/arterial PCO2, where alveolar PCO2 was determined by either
      PETCO2 or PAECO2. During baseline ventilation, PETCO2 was 3.4 mm Hg
      (approximately 11%) greater than PAECO2. Because PEEP significantly increased the
      slope of the alveolar plateau from 28 to 74 mm Hg/L, the difference between
      PETCO2 and PAECO2 significantly increased to 6.6 mm Hg (approximately 20%
      difference). The concurrent increase in VDANAT during PEEP decreased alveolar
      tidal volume and tended to limit the overestimation of PETCO2 compared to PAECO2.
      When alveolar PCO2 was estimated by PETCO2, alveolar VD/VT was 18%, compared to
      an alveolar VD/VT of 26% when alveolar PCO2 was estimated by PAECO2. This
      difference was significantly magnified during PEEP ventilation. The
      overestimation of PAECO2 by PETCO2 can result in a falsely high assessment of
      overall alveolar PCO2. Moreover, the use of PETCO2 to estimate alveolar PCO2 in
      the determination of the alveolar dead space fraction can result in falsely low
      and even negative values of alveolar dead space.

PMID- 8561344
TI  - The effect of increase in end-tidal carbon dioxide on lower esophageal sphincter
      tone.
AB  - The lower esophageal sphincter is composed of smooth muscles and is the main
      barrier against regurgitation during anesthesia. As smooth muscles are usually
      sensitive to CO2, we investigated the response of lower esophageal sphincter
      pressure to varying concentrations of CO2 in six anesthetized pigs using a
      manometric method. CO2 was increased by increasing the dead space at the Y piece
      of the ventilator. Basal values for ETCO2 were 35 +/- 2 mm Hg, reaching 62 +/- 1
      mm Hg at the end of the study (P < 0.03). In response to the increase in ETCO2,
      no change in lower esophageal sphincter pressure was noted (12 +/- 3 mm Hg vs 13
      +/- 4 mm Hg). These findings indicate that the lower esophageal sphincter is not
      affected by CO2 in the range usually encountered in clinical practice.

PMID- 8561345
TI  - Oscillometric blood pressure measurements by different devices are not
      interchangeable.
AB  - Blood pressure (BP) is frequently measured in patients by noninvasive blood
      pressure (NIBP) monitors. Values obtained by oscillometric devices of different
      brands may appear in one patient's record as if they were interchangeable; their
      concordance, however, has not been established. In 25 patients with major
      depression who were treated with electroconvulsive therapy (ECT) BP was measured
      on either arm by devices manufactured by SpaceLabs (SpL, 12 patients, 182 data
      points) and Marquette (Marq, 13 patients, 193 data points), respectively, and
      comparisons were made with simultaneous measurements on the opposite arm by
      Dinamap 1846SX (DIN), during the awake state and at 1-min intervals up to 5-7 min
      after ECT. Because ECT is associated with an intense, but short-lasting
      hyperdynamic state, comparisons of BP values could be made over a wide range of
      pressures. Bland-Altman plots were constructed to show the distribution of
      pressure differences at all pressures. Agreements between two instruments were
      judged according to guide lines by the American Association for Advancement of
      Medical Instrumentation (AAMI). The standard deviation of the difference (SDD)
      between two DIN devices was 7 mm Hg for systolic (SBP) and 6.3 mm Hg for
      diastolic blood pressure (DBP), whereas mean differences were 0.9 and 0.2 mm Hg,
      respectively (P = not significant [NS]), thus showing reproducibility.
      Corresponding SDD values SpL versus DIN were 9.1 for SBP and 8.3 mm Hg for DBP,
      while the mean differences were 1.6 (P = 0.026) and 7.3 (P = 0.0001) mm Hg,
      respectively. Corresponding SDD values for Marq versus DIN were 11.8 and 9.7 mm
      Hg with mean differences of 0.8 (P = NS) and 0.3 (P = NS) mm Hg. Whereas SBP
      differences DIN versus DIN exceeded 10 mm Hg in only 10% of observations, they
      exceeded that threshold in 31% and 32% of observations for SpL versus DIN and
      Marq versus DIN, respectively. In view of the variability that exceeds the AAMI
      guidelines and the one out of three occurrence of individual SBP differences
      exceeding 10 mm Hg for comparisons of SpL or Marq versus DIN, measurements by
      these three oscillometric devices are not interchangeable.

PMID- 8561346
TI  - Responses to nondepolarizing neuromuscular blockers and succinylcholine in von
      Recklinghausen neurofibromatosis.
AB  - Patients with type 1 neurofibromatosis (NF-1) have been reported to have
      prolonged responses to nondepolarizing (ND) neuromuscular blockers (NMBs).
      Responses to succinylcholine (SCh) have been described as increased, decreased,
      or normal. The purpose of this study was to assess responses to NMBs in NF-1
      patients in order to determine the clinical significance of abnormal responses.
      We retrospectively identified all NF-1 patients who received anesthetics at
      Strong Memorial Hospital between January 1, 1984 and December 31, 1994. We then
      reviewed all anesthetic records to classify responses to NMBs as normal,
      abnormal, or indeterminate. Records of 114 anesthetics provided to 44 NF-1
      patients were reviewed. Nondepolarizing NMBs were used during 73 anesthetic cases
      in 38 patients. Responses were normal in 69 cases and indeterminate in 4 (3 in
      patients with normal responses during other anesthetics). SCh was used during 42
      anesthetic cases in 23 patients. Responses were normal in all but one case
      (indeterminate) in a patient who had had other documented normal responses.
      Standard milligram per kilogram doses of NMBs were used in all cases, and in none
      was there evidence of abnormal response. The risk of abnormal response to NMBs in
      individuals with NF-1 appears to be minimal. We recommend no alteration in dosing
      of either SCh or ND NMBs in patients with NF-1.

PMID- 8561347
TI  - Neither skin tests nor serum enzyme-linked immunosorbent assay tests provide
      specificity for protamine allergy.

PMID- 8561348
TI  - Blood substitutes: fluids, drugs, or miracle solutions?
AB  - Oxygen-carrying volume-expanding solutions that can sustain life in the absence
      of red blood cells have been developed. Concerns about side effects, sources of
      hemoglobin, and the ultimate demonstration of efficacy will have to be
      satisfactorily addressed before anesthesiologists routinely administer such
      solutions in place of red cells during surgery.

PMID- 8561349
TI  - Permanent unilateral vestibulocochlear dysfunction after spinal anesthesia.

PMID- 8561350
TI  - Intrathecal bleeding after the intraoperative use of heparin and urokinase during
      continuous spinal anesthesia.

PMID- 8561351
TI  - Prone position: visceral hypoperfusion and rhabdomyolysis.

PMID- 8561352
TI  - Mitral valve replacement in a patient with acute intermittent porphyria.

PMID- 8561353
TI  - Unexplained transient postoperative myocardial dysfunction in a previously
      healthy child.

PMID- 8561354
TI  - Jugular venous desaturation due to epidural hematoma after craniotomy.

PMID- 8561355
TI  - Unexpected difficult tracheal reintubation after thyroglossal duct surgery:
      functional imbalance aggravated by the presence of a hematoma.

PMID- 8561356
TI  - Effects of temperature and propofol on hepatic blood flow.

PMID- 8561357
TI  - Another use of the intravenous regional block technique.

PMID- 8561358
TI  - What to do when your patients outweigh your scales--another alternative.

PMID- 8561359
TI  - Infection control precautions and anesthesia.

PMID- 8561360
TI  - Ketorolac and platelet function.

PMID- 8561361
TI  - Latex allergy and plastic syringes.

PMID- 8561362
TI  - Transesophageal atrial pacing in patients with nasal- or oral-gastric tubes.

PMID- 8561363
TI  - On rotating the epidural needle.

PMID- 8561364
TI  - The laryngeal mask airway for stereotactic implantation of fetal hypophysis.

PMID- 8561365
TI  - Mechanical chin support during general anesthesia.

PMID- 8561366
TI  - The safety of sevoflurane has not been adequately established.

PMID- 8561367
TI  - Intraarticular ketorolac.

PMID- 8561368
TI  - Combined spinal epidural anesthesia: a new "hanging drop".

PMID- 8561369
TI  - Influence of anesthetics on formation of brain edema.

PMID- 8561370
TI  - Reflux of gastric acid and tracheal stenosis.

PMID- 8561371
TI  - Optic nerve injury: role of the anesthesiologist?

PMID- 8561372
TI  - Inadvertent extubation in infants fails to trigger the low pressure alarm of the
      Ohmeda Model 7000 anesthesia ventilator.

PMID- 8561373
TI  - Blood pressure monitoring in hemiplegic patients.

PMID- 8561374
TI  - Calcium administration in rhabdomyolysis may be detrimental.

PMID- 8561375
TI  - Direct laryngoscopy with the aid of a fiberoptic bronchoscope for tracheal
      intubation.

PMID- 8561376
TI  - Propofol concentrations--an alternative explanation.

PMID- 8561377
TI  - The level is TEE-FORE.

PMID- 8561378
TI  - The destructiveness of perfectionism. Implications for the treatment of
      depression.
AB  - Reports in the public media indicate that intense perfectionism and severe self
      criticism played a role in the suicide of three remarkably talented individuals.
      The role of perfectionism in these suicides is consistent with recent extensive
      investigations of aspects of perfectionism as well as further analyses of the
      NIMH Treatment of Depression Collaborative Research Program (TDCRP), indicating
      that intense perfectionism interfered significantly with therapeutic response in
      the various brief treatments for depression. Self-critical individuals, however,
      made substantial improvement in long-term intensive treatment. These findings
      suggest the value of considering psychopathology, especially depression, from a
      psychological rather than a symptomatic perspective; that different patients may
      be differentially responsive to various types of therapy; and that more extensive
      therapy may be necessary for many highly perfectionistic, self-critical patients.

PMID- 8561379
TI  - APA-accredited predoctoral internships for doctoral training in psychology: 1995.

PMID- 8561380
TI  - The effectiveness of psychotherapy. The Consumer Reports study.
AB  - Consumer Reports (1995, November) published an article which concluded that
      patients benefited very substantially from psychotherapy, that long-term
      treatment did considerably better than short-term treatment, and that
      psychotherapy alone did not differ in effectiveness from medication plus
      psychotherapy. Furthermore, no specific modality of psychotherapy did better than
      any other for any disorder; psychologists, psychiatrists, and social workers did
      not differ in their effectiveness as treaters; and all did better than marriage
      counselors and long-term family doctoring. Patients whose length of therapy or
      choice of therapist was limited by insurance or managed care did worse. The
      methodological virtues and drawbacks of this large-scale survey are examined and
      contrasted with the more traditional efficacy study, in which patients are
      randomized into a manualized, fixed duration treatment or into control groups. I
      conclude that the Consumer Reports survey complements the efficacy method, and
      that the best features of these two methods can be combined into a more ideal
      method that will best provide empirical validation of psychotherapy.

PMID- 8561381
TI  - The reflective educator.
AB  - Since the Boulder conference on training in clinical psychology in 1949, at least
      13 national conferences have been convened to examine issues in training for
      practice in psychology, all based on the assumption that extensive training is
      required to develop professional skills in psychotherapy, psychodiagnosis, and
      related professional functions. This assumption is challenged by a large body of
      research that fails to show any relationship between training and efficacy in
      common forms of practice. Educators of professional psychologists are urged to
      heed the challenge closely and examine its implications critically. At the same
      time, educators of researchers in psychology are encouraged to examine common
      assumptions about the nature of practice in psychology and to consider
      conceptions of professional work that emphasize reflection in action and
      disciplined inquiry, rather than psychotherapy and psychodiagnosis, as defining
      features. Education for practice is neither science nor art, but a profession in
      itself. When the educational process is approached from this vantage point, novel
      opportunities for systematic investigation emerge. Decisive studies of the
      appropriate kind have yet to be done.

PMID- 8561382
TI  - Bridging scientist and practitioner perspectives in clinical psychology.
AB  - Literature suggests that a complex and often hostile relationship exists between
      the science and practice of clinical psychology. Contributors to this conflict of
      viewpoints are reconsidered within the proposition that there are different roads
      to discovery and that there may be good reasons to keep the science and practice
      of clinical psychology somewhat separate. Results of a national survey of 325
      psychologists are reviewed that support the view that psychological practitioners
      value research and consider their practices to be augmented by scientific
      findings. However, they are in need of vehicles of communication that will help
      them translate scientific findings into practice. Results suggest that
      practitioners do more to understand scientific findings than scientists do to
      understand the problems that face clinical practitioners. Ways to facilitate
      communication between and among these groups are considered.

PMID- 8561383
TI  - The local clinical scientist. A bridge between science and practice.
AB  - The local clinical scientist brings the attitudes and knowledge base of the
      scientist to bear on the problems that must be addressed by the clinician in the
      consulting room. The problems of inadequate generalizability are reduced by a
      recognition of the value of local observations and local solutions to problems.
      However, these observations and solutions benefit by the scientific attitude of
      the clinician and are subjected to the same need for verifiability that greets
      all scientific enterprises. The clinical setting is viewed as analogous to a
      scientific laboratory, and, by doing so, the scientist-practitioner model is
      enacted.

PMID- 8561384
TI  - [Handling of biological material before trace element determination].
AB  - The various steps of the analytical process are taken into account with
      particular reference to problems arising in sampling biological materials, their
      storage, pretreatment, digestion (when necessary) and determination. Emphasis is
      laid on the fact that the availability of analytical equipment with exceptional
      detection power is not always flanked by an equivalent ability to control
      phenomena of contamination and/or loss of analytes as well as to check and
      guarantee the accuracy of experimental data. In this context, proper use of the
      most popular analytical techniques for the determination of trace elements and
      the adoption of strict procedural conditions for data reliability are briefly
      discussed.

PMID- 8561385
TI  - [Assessment of factors causing pre-analytic variabililty].
AB  - Preanalytical variability can affect the results of trace element determinations.
      Even using sensitive and reliable analytical methods, the analysis of a
      contaminated specimen can only lead to erroneous results. Analyte contents in a
      sample can be altered during collection, storage and pretreatment, including
      simple dilution. Anticoagulants, plastic and glassware used for collection and
      storage, reagents, including water, and the laboratory environment itself, under
      particular conditions, can significantly contribute to this variability. The most
      common sources of contamination of biological matrices and some preventive
      measures are discussed. Operative procedures for the collection and storage of
      biological samples, specifically designed in dependence of analyte and matrix
      type, are reported.

PMID- 8561386
TI  - [Instrumental analysis of trace elements].
AB  - The study of trace elements in human medicine and toxicology requires very low
      concentration of these elements to be determined in biological matrices. Among
      the analytical methodologies of major impact there are isotopic dilution mass
      spectrometry, neutron activation analysis, anodic stripping voltammetry,
      inductively coupled plasma atomic emission spectrometry and electrothermal
      atomization atomic emission spectrometry. This last, in particular, provides high
      sensitivity and reliability for the determination of numerous elements.
      Instrumental and methodological improvements leading to these achievements
      include the adoption of the so-called stabilized temperature platform furnace,
      the introduction of universal matrix modifiers, oxygen charring steps and
      background correction systems based on the Zeeman effect.

PMID- 8561387
TI  - [Potential and limitations of neutron activation analysis methods for measuring
      elements of toxicological and environmental interest].
AB  - Merits and limits of neutron activation analysis are presented for the various
      classes of biological and environmental matrices and depending on the analytes to
      be quantified. In this framework the cases of mercury, cadmium, copper, arsenic,
      chromium, iodine are discussed in detail with particular reference to the most
      frequent analytical interferences and procedural pitfalls in sample pretreatment.

PMID- 8561388
TI  - [Quality control for trace elements in occupational and environmental medicine].
AB  - The adoption of procedures warranting the quality of the results obtained in the
      laboratory is of the utmost importance, whatever the reason these analyses are
      required for. We discuss some of the fundamentals of quality assurance, as
      recommended by the International Federation of Clinical Chemistry, IFCC.
      Procedures for the preparation of control and calibration materials, the
      evaluation of analytical methods and the assessment of laboratory performance by
      means of internal quality control procedures, including control charts, are
      reviewed. Finally, we report the organisation and the strategies use in
      programmes for external quality assurance for the determination of trace elements
      in biological fluids.

PMID- 8561389
TI  - [Reference materials and trace element analysis].
AB  - The use of appropriate reference materials allows the accuracy of analytical
      determinations to be assessed. The present availability of certified reference
      materials not always can adequately meet the needs of research in the field of
      trace and ultratrace element analysis, in particular as regards complex matrices,
      such as biological and environmental materials. In this context the various
      definitions of a reference material are discussed. Planning and certification of
      novel certified reference materials cannot disregard the exigency of obtaining
      more qualified information on the analytes, especially in so far as their
      different chemical species are concerned.

PMID- 8561390
TI  - [Reference values for trace elements in biological fluids].
AB  - The assessment of reliable reference ranges for the concentrations of elements in
      biological fluids is necessary to evaluate the risks deriving from occupational
      and environmental exposure. For the production of reference ranges in this field
      it is necessary to adhere to strict criteria for the selection of individuals,
      the procedures for sample collection, the control of analytical variability and
      the statistical treatment of results. The factors affecting analytical and
      biological variability of the concentrations to be determined, such as the route
      of absorption, the presence of sources of environmental pollution in certain
      areas of residence, physiological variables and life-styles, are discussed.

PMID- 8561391
TI  - [Trace elements: biological role and nutritional aspects for humans].
AB  - The methodological approaches generally adopted to ascertain the essentiality of
      trace elements present in human beings at levels of the order of magnitude of 1
      micrograms g-1 or less are illustrated. An element is recognized as essential
      when it has a well defined function (as stabilizer, structural, hormonal or as
      enzymatic cofactor) and when it is always present in tissues and organs in well
      defined concentration ranges, when it induces reproducible physiological effects,
      when it is possible to prevent and treat consequences due to its deficiency by
      its supplementation. For the trace elements Co, Cr, Cu, Fe, I, Mn, Se and Zn a
      short summary of their biological functions in humans is presented. In
      particular, for each element an account is given of the mean total quantity
      accumulated by the human body, the distribution in the main organs, the most
      important pathways for their uptake and the recommended daily intake. These last
      values obviously do not take into consideration the synergic or antagonist action
      due to the intake of other substances that very often can modify the absorption
      and the metabolism of the element considered.

PMID- 8561392
TI  - [Toxicity of chemical elements].
AB  - A survey is presented of the most important facets of toxicity due to chemical
      elements as well as of the mechanisms through which it may be triggered. In
      particular, a detailed discussion is made on the characteristics shown by
      arsenic, cadmium, chromium, lead, mercury, barium and beryllium, with specific
      reference to the influence exerted by physiological, environmental and life-style
      factors.

PMID- 8561393
TI  - [Platinum-based antineoplastic agents: biomedical applications and therapeutic
      aspects].
AB  - A survey of investigations performed over the last decade concerning analytical,
      clinical and pharmacological data on cancer chemotherapy with Pt-based drugs is
      reported. From this standpoint discussion focuses on clinical studies aimed at
      evaluating therapeutic response and toxicity during regional and systemic
      treatment of cisplatin against solid tumors in adults as well as in children.
      Concurrent treatments with locoregional hyperthermia in the case of limb tumors
      or with radiotherapy in the case of lung carcinoma are also dealt with.

PMID- 8561394
TI  - [Some medico-psychological perspectives on sexual homicides. Three cases].
AB  - While sexual murders are widely reported in the media, there are almost no
      reports on these major crimes in the French medico-psychological literature.
      After a brief historical and legal overview, the author discusses the forensic
      definition of sexual homicides, parent-to-child transmission of sexual violence,
      the distinction between paraphilic and non-paraphilic sexual offenders, criminal
      affects, and the classification of aggressors in violent homicides. He confirms
      that particularly violent murderers may be divided into two psychiatric and
      behavioral categories. Next, the six main causes of sexual homicide are presented
      together with three clinical observations of such cases: 1) one with homosexual
      connotations; 2) another through hate for women; 3) and a third where rage was
      not specifically directed. Finally, the author concludes that there should be
      systematic criminologic research in France into sexual murders.

PMID- 8561395
TI  - [Study on the prevention of HIV transmission between patients in the psychiatric
      hospital milieu].
AB  - A survey of staff opinion using anonymous questionnaires was conducted
      simultaneously in five French psychiatric hospitals in January and February 1995.
      The 36 questions concerned collective HIV prevention practices for hospitalised
      patients, actual participation in various actions, and personal choice and
      judgement concerning prevention strategies, especially with regard to sexual
      transmission. The paper gives an initial data analysis of the 1473 questionnaires
      collected. In general, psychiatric hospital staff feel concern for AIDS issues
      and seem to be already involved in specific prevention strategies.

PMID- 8561396
TI  - [Identification of subgroups of schizophrenic patients by a typological
      analysis].
AB  - The existence of two subtypes of schizophrenia (positive and negative) is well
      established. The evidence in favour of other subtypes, in particular a
      disorganized subtype, is still the subject of some debate. Therefore, the aim of
      the study was to investigate the possibility of further subtypes of schizophrenia
      by applying a Ward's method of cluster analysis with the Positive And Negative
      Syndrome Scale (PANSS) scores in 138 schizophrenic patients. The results from the
      cluster analysis suggested the existence of at least four sub-types of
      schizophrenia, positive, negative, mixed and disorganized. Evidence for the
      validity of these subtypes was provided by the observed differences between the
      clusters on a number of clinical characteristics. Thus, the negative-positive
      dichotomy in schizophrenia is an oversimplification, and the existence of a more
      complex structure needs to be taken into account in future research.

PMID- 8561397
TI  - [Theoretical bases for the creation and functioning of a health institution for
      dysthymic states].

PMID- 8561398
TI  - [Anhedonia and sensation seeking].
AB  - The relationship between anhedonia and sensation seeking has been studied in 56
      normal subjects of both sexes (33 males, 23 females). Anhedonia and sensation
      seeking were respectively defined by two reliable rating scales: Physical
      Anhedonia Scale of Chapman (PAS), Zuckerman's Sensation Seeking Scale (SS form V 
      40 items). The results have shown a negative correlation between this scales for
      males but not for females. These finding suggest that lowered levels of sensation
      seeking could constitute for males, like anhedonia, a risk factor of
      schizophrenia.

PMID- 8561399
TI  - [Reflections on international adoption].
AB  - In paediatric psychiatry, we often encounter French families who have chosen for
      international adoption of foreign children. From our clinical cases and a review
      of the literature, we have cited several circumstances which can lead to
      separation following adoption, either due to a rejection of the adopted by the
      adopting family or vica-versa: cases in which the adopted children are older or
      even young adolescents, simultaneous adoption of more than one child, adoption of
      psychologically disturbed children with a history of neglect or abuse by a
      previous guardian, cases in which the adopting parents are inadequately prepared
      due to international adoption procedures allowing the rapid accession of the
      adoption and cases with a poor understanding of the adoption legislation on the
      part of the biological parents or the child being adopted. These risque factors,
      relatively specific to international adoption, can in isolation or by a
      combination of factors lead to failure in the adoption. Subsequent separation
      after adoption often leads to institutionalization and further rejection.

PMID- 8561400
TI  - [Use and value of the therapeutic neuroleptic-bromocriptine combination in
      schizophrenia].
AB  - Use and interest of therapeutic association bromocriptine-neuroleptic in
      schizophrenia. Twelve schizophrenic patients were treated by bromocriptine (7.5
      mg.day) and neuroleptic. After one month, patients on this treatment showed a
      mean improvement of 29% on the total score of the positive and negative symptom
      scale. This results suggest that therapeutic association bromocriptine
      neuroleptic may be used for schizophrenic patients.

PMID- 8561401
TI  - [Mental representation of drugs: construction of two questionnaires to study
      patients treated with psychotropic or oral hypoglycemic drugs].
AB  - We have built two questionnaires in order to study the representation of drugs.
      Questionnaires have been established according to the results of an open study
      involving 78 subjects, whether receiving a treatment or not. These questionnaires
      were applied on a sample of 126 (psychiatric or diabetic) patients. In the
      future, we expect the questionnaires to help studying relationships between drugs
      representation and compliance.

PMID- 8561402
TI  - [Communication in the patient care team about palliative situations' results of a
      survey at the Laennec Hospital, Paris].
AB  - The authors report results from a sample survey in a university hospital in
      connection with the aspects of communication in medical team about paliative
      situations. The questionnaire, made from a paliative care group, consults the
      usual practices and during crisis just as patient is dying, in a curative medical
      care. Hospital is not a place to die. Difficulty in survey are probably in
      keeping with individual and collective defences opposite to dying patient.

PMID- 8561403
TI  - [Hybrid pathologies: difficulties in intricate clinical cases].
AB  - Following two cases of young patients, issued of african immigration or mixed
      franco-african couple, and presenting antisocial acts, the authors are wondering
      about the relationship between identity and ethnic troubles. They think it may be
      a clinical "message" of troubles, joining cultural distress and separation
      anxiety, on an obvious oedipian found.

PMID- 8561404
TI  - [Stabilized psychoses and psychopathology].
AB  - After many years of psychotic evolution, many patients reach a degree of
      stability which, without being the equivalent of autonomy, enables them to
      maintain a psychological and behavioral equilibrium if the psychiatric and social
      services may fit for the particularities of each case. Thus, psychosis may remain
      stable within its socio-dependence, if management is adapted to its structure and
      history, and finally to its vulnerability and predispositions.

PMID- 8561405
TI  - [Family therapy in the management of schizophrenic patients].
AB  - Family Therapies, as particular modalities of schizophrenic patients' treatment,
      may have a great significance in the requalification of the competences and
      responsibilities of people who are affected by the problem, i.e. members of the
      family and professional actors (psychiatrists, psychotherapists, etc.). Through
      three cases, the present paper proposes some practical and theoretical principles
      which allow to set this form of therapy in this kind of disorders.

PMID- 8561406
TI  - [From Aboriginal psychological medicine to modern psychiatry in Peru].
AB  - It is traced a succinct development of the Peruvian Psychiatry beginning in the
      Ancient Peru (aborigen psychological medicine) with the pre-Inca and Inca
      periods. The most important sources of that epoch are the spanish chronicles and
      also the archeological and ethnological evidences. Then, it is presented the
      psychiatry evolution during the colonial and post-colonial time, and finally
      modern psychiatry in Peru.

PMID- 8561407
TI  - [Cholesteatoma in children. Apropos of 110 cases].
AB  - This retrospective study of 110 middle ear cholesteatomas, concerning children up
      to 15 years old which have been treated between 1982 and 1992 in the ENT
      department of the university hospital of Strasbourg, analyzes the particularities
      of this disease and the therapeutic strategy adopted. The evolution of middle ear
      cholesteatoma is more rapid in childhood than in adulthood, due to greater growth
      potential of tissue in childhood, persistence of Eustachian tube dysfunction and
      aggressive extension in middle ear. The surgical removal is said to be difficult
      with numerous postoperative recurrences. Closed technique tympanoplasty was used
      for 47 cholesteatomas (43%), with a postoperative recurrence rate of 54%. An open
      technique was used for 63% cholesteatomas (57%), with a recurrence rate of 29%.
      The postoperative follow up has to be continued as long as possible, whatever the
      technique used may be.

PMID- 8561408
TI  - [Congenital cholesteatoma and associated ossicular malformations].
AB  - 15 cases of congenital cholesteatoma surgically treated from 1982 to 1992 are
      presented. Clinical diagnosis criteria, pathology, localisations and extensions
      to the middle ear are analyzed. Ossicular malformations were associated in one
      third of the patients of this series. These ossicular malformations underscore
      the congenital origin of such cholesteatoma. A review of the literature and
      pathogenesis of congenital cholesteatoma is discussed.

PMID- 8561409
TI  - [Predictive factors of residual cholesteatoma in children].
AB  - The decision on the appropriate surgical technique for treating cholesteatoma in
      children raises a number of controversial questions, most because of personal
      convictions rather than because of established data. We attempted to determine
      which patients are at risk of residual cholesteatoma in order to propose the most
      rational therapeutic strategy. A retrospective study of 250 children with
      cholesteatoma or severe retraction underwent surgery between 1986 and 1992.
      During this period 69 cases of residual cholesteatoma were recorded during a
      second intervention. After a mean follow-up of 33 months after the final
      operation, the Kaplan-Meier plot shows a rate of 31% and 34% at 3 and 5 years
      respectively. The univariate and multivariate (Cox regression) analysis was
      performed to search for a correlation between residual cholesteatoma development
      and past history including type of process involved, peroperative findings and
      surgical technique. Three factors were closely and independently related (p <
      0.003) to residual cholesteatoma: invasion of the posterior middle ear, presence
      of ossicular erosion after excision and presumption of incomplete ablation.
      Inversely, age, surgical history, extension and nature of the process involved as
      well as surgical technique had no effect on development of residual
      cholesteatoma. Only one comparable study has been published where only ossicular
      erosion was found to be significant on multivariate analysis. The presence of one
      or more of the three of the factors mentioned above should lead to a second
      intervention, perhaps after a short delay, whatever the initial technique (open
      or closed).

PMID- 8561410
TI  - [Latent, non-suppurative mastoiditis. Apropos of 62 cases].
AB  - The term masked mastoiditis defines a subclinical infectious inflammatory process
      of the mucosal lining and bony structures of the mastoid air cells with an intact
      tympanic membrane. The disease follows an apparently well treated recent acute
      otitis media. Probably due to an anaerobic colonizing flora, the developing bone
      infection is of low grade without pus formation. The clinical features of the
      disease are not overt as those in coalescent mastoiditis. The intact ear drum
      does not reflect the severity of bone eroding disease which is characterized by
      non-exudative but proliferative changes. Hence there is no pus formation. The
      incidence of complications is high. Plain X-ray film and CT scan do not
      specifically define the disease process. Bone scan indicates the bone invading
      nature of the mastoid infection. The osteoblastic reaction secondary to osteitis
      is demonstrated by the high uptake of the isotope in the involved mastoid.
      Antibiotics may cure the disease process but in most of the cases surgery in
      unavoidable.

PMID- 8561411
TI  - [Laryngeal stenosis in children. Evaluation of 10 years of treatment].
AB  - Over a 10 year period from 1984 to 1994, 98 children underwent curative treatment
      for sub-glottal stenosis of the larynx at La Timone Hospital in Marseille,
      France. Eighty-two patients were operated on via an external approach. An
      endoscopic procedure with the CO2 laser was used in 16 cases. The majority of the
      children had acquired stenosis (77%), with greater than 70% obstruction (65%),
      and were under 5 years of age (60%). The details of the different therapeutic
      techniques used are presented. The laryngotracheoplasty technique used to widen
      the larynx (n = 58) with an autologous rib cartilage (n = 53) is the most
      important current progress. The possibilities for laryngotracheofissure (n = 21)
      and cricotracheal resection (n = 3) are also discussed. After decannulation, 95%
      of the children could breath normally via the natural airways. The quality of the
      outcome was not dependent on the therapeutic method used. Perspectives for new
      methods or modifications of existing methods are discussed.

PMID- 8561412
TI  - [Ambulatory laser and turbinectomy in the treatment of nasal obstruction. Apropos
      of 68 cases].
AB  - The purpose of this prospective study was to compare subjectively and objectively
      the efficiency of laser vaporisation against surgical procedure in treatment of
      nasal obstruction related to vasomotor rhinitis. 40 inferior nasal turbinates
      laser vaporisations were compared to 28 surgical inferior turbinectomies. This
      trial was based on rhinomanometric data before and after laser or surgical
      management and on appreciation of individual nasal comfort. The results obtained
      with conventional surgery were slightly better than laser vaporisation; however
      this new procedure succeed in 75% of cases with a mean of one year follow-up. The
      rhinomanometric++ findings appeared especially contributing when significant
      disorders exist before treatment.

PMID- 8561413
TI  - [Osteoma of the frontal sinus. Apropos of 10 cases].
AB  - The authors report 10 cases of frontal sinus osteoma. The patient group consisted
      of 5 men and 5 women, ranging in age from 15 to 60 years. The most common
      revelating symptom was headache. Treatment depends on tumor size, its course, and
      complications. Transfacial incision was used in 3 cases and Cairns Unterberger
      approach in 5 cases. Post operatively anatomic and esthetic results were good,
      without recurrences.

PMID- 8561414
TI  - [Primary lymphoma of the sphenoid sinus. Report of a case and review of the
      literature].
AB  - The Authors describe a case of primary isolated non-Hodgkin lymphoma with
      sphenoidal presentation. According to literature, this is the third specification
      quoted in the whole world. The diagnostic approach for this clinical entity is
      emphasized, stressing the importance of the complete radiological and endoscopic
      work-up.

PMID- 8561416
TI  - [Role of extracorporeal shock wave lithotripsy in the treatment of common bile
      duct and intrahepatic calculi].
AB  - The management of intrahepatic and common bile duct stones has been modified by
      the advent of endoscopic sphincterotomy and percutaneous extraction through a T
      tube tract or transhepatic access. Occasionally, nonoperative extraction is
      incomplete. The use of extracorporeal lithotripsy is reviewed in this setting.
      From May 1990 to February 1994, 18 patients (age 68.4 +/- 4.6 years) were treated
      by extracorporeal shockwave lithotripsy combined with endoscopic sphincterotomy
      and retrograde extraction or percutaneous approach. 72% of patients had
      previously undergone a cholecystectomy and 44% exploration of the common duct.
      Patients were submitted to 1.56 +/- 0.17 session of lithotripsy (5.546 +/- 701
      shockwaves). Hospital stay was 19.5 +/- 3.3 days. After the lithotripsy, 1.17 +/-
      0.19 endoscopic or percutaneous procedures per patient were necessary to clear
      the biliary tract. Seventy-eight percent of patients became stone-free. The five
      failures were treated by endobiliary prosthesis (n = 4) or cholecystectomy and
      bile duct exploration (n = 1). Lithotripsy in association with the usual
      therapeutic modalities contributes to clearing the bile duct from stones and
      avoids surgery in the majority of patients. A multidisciplinary approach is
      necessary in order to obtain those results.

PMID- 8561417
TI  - [Dilatation enteroplasty for obstructive Crohn disease. Experience of the
      University of Montreal].
AB  - Multiple small bowel resections for obstructive symptoms caused by Crohn's
      disease can lead to a short bowel and malabsorption. Preservation of intestinal
      length is possible by the use of strictureplasty. Between August 1983 and March
      1993, ninety strictureplasties were performed in 25 patients. They were 13 males
      and 12 females with a mean age of 37 years. Fourteen (56%) previously had small
      bowel resection for Crohn's disease. A mean number of 4.3 strictureplasties per
      patient were performed. Concomitant resection of bowel with active disease was
      performed in 18 patients (72%). In this series, no perioperative death occurred
      and one patient developed an enterocutaneous fistula. The overall complication
      rate was 8%. Postoperatively, 18 patients (72%) were completely relieved of
      symptoms, 6 were improved (24%) and one became worst (4%). After a 27 month
      follow-up period, the symptoms recurred in 13 patients (52%); three had no
      treatment, 7 had medical treatment and 3 required reoperation (12%). Our results
      support the safety and the use of strictureplasty for stenotic bowel lesions
      associated with Crohn's disease.

PMID- 8561418
TI  - [Endoscopic YAG laser and palliative therapy of cancer of the esophagus].
AB  - In our institution, the YAG laser has been used to treat 110 patients with
      inoperable esophageal carcinoma. Therapy was palliative as patients presented
      metastases (41.8%), advanced systemic disease (22.7%), extensive local disease
      (18.2%) or recurrent carcinoma (10%). The study group included 92 men (mean age
      68.4 years) and 18 women (mean age 67.0 years); 47.3% of the patients had
      received no previous treatment while 52.7% had been treated previously with
      either radiotherapy, chemotherapy, surgery, stents or dilatation. The majority of
      lesions were adenocarcinomas (57.3%) with squamous cell carcinomas in 37.3%;
      66.3% of cancers were located in the distal third of the esophagus. The patients
      received a mean of 2.4 laser treatments with 4883 joules per treatment on
      average. The rate of major complications was 2.7% and the rate of mortality 1.8%.
      The median survival for the group was 4.5 months. No significant difference was
      found in the length of survival according to the histology of the tumour (p =
      0.35), the presence of metastases (p = 0.24) and the association of other
      treatment modalities with the laser (p = 0.06). Functional results were
      considered good to excellent in 82.1% of cases. In conclusion, the YAG laser does
      not influence overall survival of inoperable patients, but this therapy is
      effective and safe and is presently the treatment of choice for these patients.

PMID- 8561419
TI  - [Acute tubular necrosis in patients after kidney transplantation: associated
      factors and impact on functional survival of the graft].
AB  - Acute tubular necrosis (ATN) represents a serious problem in kidney
      transplantation. We have reviewed the causes and effects of ATN on kidney
      transplant patients treated in our hospital between June 1981 and December 1992.
      We analyzed 359 consecutive kidney transplants performed in 338 patients (213
      male and 125 female). There were 311 first grafts. The actuarial functional graft
      survival (AFGS) was 85% at 1 year and 58.2% at 10 years. The incidence of long
      term chronic rejection, the 1-year creatinine blood level (CBL) and the AFGS are
      summarized: [table: see text] The donor age and the PRA level were significantly
      correlated with ATN occurrence. ATN after transplantation was associated with a
      poorer function and survival of the kidney graft. Better donor and patient
      selection could decrease the occurrence of ATN, thus improving the graft outcome.

PMID- 8561420
TI  - [Usefulness of prostate-specific antigen in the diagnosis of lymphatic metastases
      in cancer of the prostate].
AB  - PSA has become the most important tumor marker in prostate cancer and has
      increased its usefulness from simply being a marker of treatment response, to one
      of early detectible/screening, and more recently as an aid in staging. Lymph node
      status in patients with prostate cancer is extremely important in terms of
      prognosis and treatment. We therefore undertook this study to evaluate the
      predictive value of PSA in determining lymph node status in an attempt to limit
      the number of lymph node dissections. The study consists of 240 consecutive cases
      of prostate cancers having pre op PSA levels, negative bone scans and known lymph
      node status (determined by lymphadenectomy). Results showed that the risk of node
      positive disease highly correlated with PSA levels and poorly correlated with
      clinical stage and histologic grade. There was no minimal PSA level under which
      nodes were consistently negative. With PSA under 10, 7.7% of lymphadenectomies
      revealed at least one positive node (2 cases had PSA's of 3). When PSA was
      between 10 and 20, 17% had positive nodes, with PSA between 20 and 50, 21% were
      node positive, and 53% positivity when PSA was over 50. The combination of low
      grade tumors with PSA under 20 identified a subgroup of patients with
      consistently negative nodes. We therefore conclude that PSA levels may be of use
      in predicting lymph node status but cannot, at present, be used to replace
      lymphadenectomy.

PMID- 8561421
TI  - [Lich-Gregoir ureteroneocystostomy: experience of a North-American pediatric
      center].
AB  - Between August 1990 and December 1993, 140 children underwent Lich-Gregoir
      antireflux plasty. Twenty-eight boys and 112 girls were included with an age
      range of 4 months to 15 years (average 5.8 years). Twenty-seven of 220 ureters
      reimplanted were duplicated. At 6 months follow-up, 10 of 140 children had
      persistent reflux and 5 had controlateral reflux. Two patients had obstruction
      and 1 needed reintervention. At 1 year follow-up, only 3 children had persistent
      reflux and none controlateral. The Lich-Gregoir antireflux procedure is a simple
      surgery with minimal morbidity and excellent success rate.

PMID- 8561422
TI  - [Cyclosporine A decreases coronary blood flow in dogs].
AB  - The objective of the present study was to determine the effect of cyclosporine
      (CSA) on coronary artery reactivity. Six mongrel dogs, weighing 20 to 30 kg were
      anesthetized with sodium pentobarbital and were artificially ventilated. A median
      sternotomy was performed to expose the heart. Left anterior and circumflex
      coronary flows were measured with an electromagnetic flowmeter. Heart rate, mean
      arterial pressure, coronary sinus pressure and dP/dt were monitored during all
      experiments. Blood samples were withdrawn from the coronary sinus to measure CSA.
      Injections of 5 and 10 mg of CSA in the left anterior descending coronary artery
      were administered to all animals and the measure of the circumflex coronary blood
      flow was used as control during the experiments. The decrease in left anterior
      descending coronary artery blood flow averaged 24 +/- 9% (p = 0.002) and 18 +/-
      11% (p = 0.009), and the increase in coronary vascular resistance averaged 31 +/-
      12% (p = 0.005) and 16 +/- 24% (p = 0.1) after 5 and 10 mg of CSA, respectively.
      There were no significant changes in circumflex coronary artery blood flow and in
      dP/dt during the experiments. Cyclosporine blood levels averaged 453 +/- 226
      nmol/l and 1087 +/- 199 nmol/l after injections of 5 and 10 mg of CSA,
      respectively. In conclusion, this study suggests that CSA can cause acute
      vasoconstriction of the arterial coronary vasculature.

PMID- 8561423
TI  - [Effects of cyclosporine A on the reactivity of the aorta with regenerated
      endothelium in rats].
AB  - Cyclosporine A (CyA) affects vascular reactivity but its effect on local vascular
      tone following endothelial regeneration is unknown. Experiments were designed to
      study the effects of CyA on endothelial and smooth muscle reactivity of
      endothelium-regenerated arteries. Three groups of rats (n = 8) were subjected to
      aortic mechanical denudation. Subsequently a first group was treated 8 weeks with
      CyA (20 mg/kg) and a second one with an equivalent volume of CyA vehicle: olive
      oil (OL). A last group was submitted to a standard diet and represented the
      control group (CTL). After 8 weeks, aortic rings were suspended in organ chambers
      for assessment of endothelial and smooth muscle function. Maximal endothelial
      dependent relaxation to acetylcholine (CyA: 52 +/- 3%, OL: 50 +/- 4%, CTL: 48 +/-
      5%; p = NS), adenosine diphosphate (CyA: 30 +/- 7%, OL: 18 +/- 2%, CTL: 24 +/-
      5%; p = NS) and histamine (CyA: 38 +/- 6%, OL: 43 +/- 4%, CTL: 47 +/- 5%; p = NS)
      were comparable among all groups. In aortic segments studies without endothelium,
      increased contraction to serotonine was significantly lessened in the OL group
      (CyA: 259 +/- 43%, OL: 153 +/- 11%, CTL: 243 +/- 24%; p < 0.05). Maximal tension
      to cumulative doses of norepinephrine was increased in rings without endothelium
      treated with CyA (CyA: 5.8 +/- 0.6 g, OL: 4.2 +/- 0.5 g, CTL: 4.0 +/- 0.2 g; p <
      0.05). All these differences were abolished in rings studied with endothelium.
      Endothelial independent relaxation to sodium nitroprusside were similar among all
      groups. In conclusion, CyA does not specifically affect endothelium-dependent
      relaxation of the regenerated aortic endothelium. However, our model suggests
      that CyA increases vascular tone mediated by increased smooth muscle sensitivity
      to norepinephrine and serotonine but these effects are prevented by the
      regenerated endothelium. This experiment demonstrates the ability of the
      regenerated endothelium to prevent CyA-induced vascular toxicity.

PMID- 8561425
TI  - [Effect of the injection of cyclosporine A on the peripheral venous resistance in
      dogs].
AB  - We have studied the effect of cyclosporin on the peripheral venous system. CSA
      was injected into an isolated hind limb saphenous vein perfused at constant flow
      in 29 dogs. Reactivity of the vein was tested with infusions of norepinephrine
      (NE) before and after CSA. In a 1st group of 7 dogs, CSA at doses of 5, 10 and 20
      mg was infused over a 10-minute period. In a 2nd group of 8 dogs, 20 mg of CSA
      was infused over 20 minutes and, injections of 6, 12 and 24 micrograms of NE were
      administered before and during CSA. In a 3rd (n = 7) and 4th (n = 7) groups of
      animals, 30 mg of CSA was injected over 60 minutes and injections of 3, 6, 12
      micrograms of NE were given before and during CSA. In the last group, an
      ipsilateral lumbar sympathectomy was performed before CSA injection. The infusion
      of CSA over periods of 10 and 20 minutes did not cause significant changes in
      venous perfusion pressure. The infusion of 30 mg of CSA over 60 minutes caused an
      increase in venous perfusion pressure from 44 +/- 2 mm Hg to 58 +/- 5 mm Hg (p <
      0.0001). Surgical sympathectomy prevented the venoconstrictor response to CSA.
      Injections of 3, 6 and 12 +/- g of NE caused averaged increases of 25 +/- 6, 39
      +/- 9 and 53 +/- 10 mm Hg before CSA, and of 45 +/- 7, 69 +/- 12 and 84 +/- 8 mm
      Hg respectively after CSA injections, a significant increase (p = 0.03). In
      conclusion, CSA causes a vasoconstriction of the saphenous vein through
      stimulation of the sympathetic nervous system and potentiates the venoconstrictor
      effect of NE.

PMID- 8561424
TI  - [In vitro endothelial dysfunction after cold storage: comparison with various
      preservative solutions].
AB  - Optimal solution for endothelial function preservation during cold storage for
      organ transplant has not yet been defined. To assess this issue, rat aortic rings
      (n = 28) were stored for 4 hours at 4 degrees C in different preservation
      solutions: Krebs Ringer (KR), normal saline (NS), rat blood (RB), and the
      University of Wisconsin solution (UW). Subsequently, rings were suspended in
      organ chambers for endothelial and smooth muscle assessment. Endothelial
      dependent relaxation responses were tested by exposure to cumulative doses of
      acetylcholine (ACH), adenosine diphosphate (ADP), and histamine (HIS). Smooth
      muscle function was evaluated by exposure to norepinephrine (NE) and sodium
      nitroprusside (SNP). A fifth group not submitted to a storage period was used as
      control (CTL, n = 7). Results are expressed as maximal relaxation (%) from
      initial precontraction level. Compared to the CTL group, all storage groups
      showed a significant decrease in endothelial-dependent relaxations to ACH, ADP
      and HIS (p < 0.05). Among the stored groups, endothelial-dependent relaxation to
      ACH was significantly decreased in the NS group when compared to the UW group (p
      < 0.05). Endothelial-independent relaxation to SNP was comparable for all groups.
      However significant hypercontractility to NE was observed for all stored groups
      compared to the control group (p < 0.01). A significant decrease in ADP response
      was observed with NS and RB storage when compared to KR (p < 0.01). In
      conclusion, cold storage affects both endothelial and smooth muscle function by
      decreasing endothelial-dependent responses to ACH, ADP and HIS and increasing
      smooth muscle reactivity to NE. However, endothelial dysfunction was lessened
      with UW or KR storage compared to NS or RB.

PMID- 8561426
TI  - [Effect of pentoxifylline on the vascular toxicity secondary to cyclosporine in
      rats].
AB  - Chronic administration of cyclosporine (CyA) has been shown to affect local
      vascular tone. Pentoxifylline (PTX), a xanthine-derived vasoactive agent, has
      been reported to prevent CyA toxicity but its effect on CyA-related increased
      vascular tone remains uncertain. In vitro experiments were designed to study the
      effects of PTX on endothelium-dependent and independent vasorelaxation of the rat
      thoracic aorta. Three groups of rats (n = 10) were respectively treated for 4
      weeks with CyA (30 mg/kg/day), CyA and PTX (40 mg/kg/day), and CyA and PTX (80
      mg/kg/day). At the end of the period, rings (4-5 mm) of aorta were harvested and
      suspended in organ chambers containing Krebs Ringer solution (37 degrees C, 95%
      O2, 5% CO2) for assessment of endothelial and smooth muscle reactivity.
      Endothelium-dependent relaxation to acetylcholine was significantly enhanced in
      animals treated with CyA and PTX (40 mg/kg/day) compared to those exposed to CyA
      alone (p < 0.05). Response to histamine and adenosine diphosphate was not
      affected. However, the use of PTX (80 mg/kg/day) significantly deteriorated the
      endothelial response to the same drugs (p < 0.05) suggesting a detrimental effect
      of PTX at this concentration. Endothelial-independent relaxation to sodium
      nitroprusside was comparable in all groups. The results suggest the clinical
      benefit reported with the use of PTX on patients chronically exposed to CyA may
      partly be due to an improvement of the vascular endothelial function. However,
      the toxicity encountered at high dose should cautioned its use in clinical setup.

PMID- 8561427
TI  - [Comparison of the infusion of acetylcholine into the artery of the sinoatrial
      node with the electric stimulation of cardiac parasympathetic nerves].
AB  - Atrial fibrillation occurring after open heart surgery largely depends on
      heterogeneous dispersion of refractoriness. To investigate the contribution of
      the autonomic nervous system in this phenomenon, we studied the regional
      distribution of neurally induced atrial electrophysiological events. Electrical
      stimulation of the right atrial fat pad, acetylcholine injection into the sinus
      node artery, and stimulation of the right and left vagosympathetic trunks were
      compared with respect to detailed atrial mapping. Unipolar electrograms were
      recorded from 127 atrial sites before and after neural stimulation or
      acetylcholine injection (10(-7) mol) in 8 anesthetized dogs. Regional changes in
      atrial repolarization were estimated by epicardial isointegral maps generated
      from computed values of the area under each electrogram and plotted on an atrial
      grid. The anatomical distribution of the sinus node artery was assessed by intra
      arterial injection of microspheres. The effects of right and left vagal and right
      atrial fat pad stimulation extended contralaterally. Acetylcholine injected into
      the sinus node artery affected the lower left atrium whereas no microspheres
      could be found in this region upon microscopic examination. Therefore, this
      effect was possibly related to cholinergic activation of neuronal cell bodies
      located in the right atrial wall and projecting to the lower left atrium,
      supporting the hypothesis that local circuit neurons were involved in the
      activation of the intrinsic nervous system of the heart.

PMID- 8561428
TI  - [Effect of solutions of preservation on the vascular reactivity of human
      saphenous veins].
AB  - It is mandatory to preserve the vascular tone regulation of the saphenous vein in
      order to optimize its performance as a vascular conduit. To determine the optimal
      preservation solution, human saphenous vein segments (3-4 cm) were harvested,
      stored for 60 minutes in different preservation solutions and studied in organ
      chambers for endothelial and smooth muscle assessment. A 1st group (n = 10) was
      stored in the heparinized blood of the patient (SH), a 2nd group (n = 10) in
      physiologic saline solution (NaCl) and a 3rd group (n = 10) in Krebs Ringer (KR)
      solution. All solutions were maintained at room temperature (21 degrees C). Each
      preserved segment was paired to a control segment, harvested in the same patient,
      and studied before storage. Following 60 minutes of preservation decreased
      endothelial-dependent relaxation to acetylcholine and histamine was observed
      among the group stored in KR (p = 0.06 and p < 0.02 respectively) compared to the
      other groups. Endothelium-independent relaxation to sodium nitroprusside was not
      affected regardless of the solution used. However, veins stored in SH disclosed
      an increased contractility to norepinephrine (p < 0.04). When intergroup
      variability was considered (by variance analysis), no significant difference was
      seen between each group. This study suggests that KR and SH were not as efficient
      as NaCl in preserving saphenous endothelial function. Furthermore, storage in SH
      increased smooth muscle response to catecholamine. In this experimental setup,
      0.9% NaCl solution is an acceptable preservation solution of the saphenous vein.

PMID- 8561429
TI  - [Effects of acute rejection on the endothelium-dependent relaxation of coronary
      arteries of the transplanted heart in dogs].
AB  - Chronic rejection has been linked to premature coronary atherosclerosis in heart
      transplantation and may be related to altered vascular reactivity. However, the
      effect of acute rejection on coronary reactivity remains uncertain. To evaluate
      this aspect, coronary artery reactivity was studied during acute rejection in a
      canine model of heart transplantation. Two groups of mongrel dogs (n = 7) (20 to
      30 kg) underwent heterotopic heart transplantation (cervical position), and
      received either no treatment (noTx) or cyclosporine (CyA), 10 mg/kg/day. On day
      7, recipient native (NH) and grafted hearts (GH) were harvested and 4-mm rings
      from the circumflex coronary artery were studied in organ chambers for
      endothelium and smooth muscle reactivity. At the harvesting, GHnoTx displayed a
      grade IV/IV histologic rejection while GHCyA (CyA dosage 250-350 nM) reached
      grade IIIa-IV. Intimal hyperplasia was found in coronary arteries of treated and
      non-treated GH [4/7 (noTx) vs 3/7 (CyA)]. Endothelium-dependent relaxation to
      thrombin was impaired in GH compared to NH and was not influenced by CyA
      treatment [EC50 (-log M): GHnoTx: 1.12 +/- 0.18 vs NHnoTx: 1.67 +/- 0.16 (p =
      0.06); GHCyA: 0.99 +/- 0.22 vs NHCyA: 1.64 +/- 0.09 (p = 0.02)]. Conversely,
      endothelium-dependent relaxation to 5-hydroxytryptamine (5-HT) was enhanced in
      both CyA-treated and noTx groups [EC50 (-log M); GHnoTx: 5.96 +/- 0.12 vs NHnoTx:
      5.54 +/- 0.14 (p = 0.046); GHCyA: 6.65 +/- 0.19 vs NHCyA: 5.66 +/- 0.16 (p =
      0.004)]. A facilitating effect of CyA on 5-HT was also seen in GH [GHnoTx vs
      GHCyA (p = 0.01)], suggesting a CyA intrinsic effect. Responses to acetylcholine
      and adenosine diphosphate were similar in all groups as well as endothelium
      independent relaxation to sodium nitroprusside and contractile response to KCl
      and PGF2 alpha. We conclude that, in our model, acute rejection does not
      specifically impair cGMP-mediated relaxation but affects in a receptor-specific
      manner the endothelium-dependent relaxation. CyA did not prevent these effects
      but furthermore appeared to enhance the coronary endothelial sensitivity to 5-HT.

PMID- 8561430
TI  - [Spontaneous dissection of the cervical arteries].
AB  - The spontaneous cervical artery dissection (SCAD) is one of the main causes of
      cerebro-vascular accident in the young adult. It may results from minor cervical
      trauma. The pathophysiological basis of the neurological complications remain
      unclear. For that reason, the treatment of SCAD is often empirical. In a
      retrospective study (1984-1994), we have reviewed 20 cases admitted to Notre-Dame
      Hospital for a SCAD confirmed by angiography. The initial clinical diagnosis was
      missed in 65% of the cases despite a suggestive symptomatology (headache 80%,
      hemiparesis 65% and Horner 45%). We have studied the clinical evolution as
      related to blood pressure, volemia, haematocrit and the administered treatment
      (aspirin, Coumadin). 60% of the patients (mean age 39) deteriorated in the hours
      following their admission. Their was one death (5%) and 85% had neurological
      sequelae. This study suggest that SCAD is a potentially serious disease. A
      delayed diagnosis may lead to a poor prognosis. Early aggressive treatment aiming
      at an optimal cerebral perfusion could improve the patients outcome.

PMID- 8561431
TI  - [Geometrical modeling of the spine and the thorax for the biomechanical analysis
      of scoliotic deformities using the finite element method].
AB  - In order to study the biomechanical behavior of the whole human spine and thorax,
      as well as orthopaedic treatment effects, a new generation model is proposed,
      which includes a precise functional representation of the posterior part of the
      spine, while respecting computational capabilities. This paper presents the
      geometrical aspects of this model. The latter is built using an hybrid method
      which combines steroradiographic 3-D reconstructions of the spine and thorax [1]
      to serial CT scan 3-D reconstructions of typical human vertebrae and sternum [4]
      and published morphometric data of ribs [2, 3]. These anatomical structures were
      deformed in order to fit as well as possible the personalized data of scoliotic
      patients using geometrical transformations as well as interpolation or
      extrapolation techniques. In the posterior part, articular facets are modelled
      and parameterized as elementary surface shapes (plane, cylinder, sphere). For the
      articular facet geometry of a given normal subject, results revealed that the
      zygapophyseal facets are better represented by planes for T1 to T11 and by
      portions of cylinders for T12 to L5, which is in concordance with the literature
      [5, 6]. Evaluation of this modelling approach was done on 2 cadaveric vertebral
      segments. Parametric data obtained from the model were compared to precise
      measurements done on the vertebrae using a 3-D digitizer, and concordance was
      found. These personalized geometric informations were then used to build a finite
      element model [7], which will be useful to study scoliotic deformities as well as
      personalized orthopaedic treatments.

PMID- 8561432
TI  - [Possible relationship between idiopathic scoliosis and morphologic somatotypes
      in adolescent females].
AB  - This retrospective study was conducted to verify the possibility of a
      relationship between morphological somatotypes and Adolescent Idiopathic
      Scoliosis (AIS). The sample was composed of 77 adolescent girls presenting
      Idiopathic Scoliosis. In every case, scoliosis was important enough to
      necessitate a corrective surgery. The control group (historical type) was taken
      from an anthropometric study done in 1990 [5]. Morphotypes were evaluated from
      medical slides with pre-established criteria based on Sheldon's technique [3, 4].
      Three somatotype values were obtained: One for ectomorphism, a second for
      mesomorphism and a third for endomorphism. This classification system is
      calibrated in a way that the summation of these 3 values necessarily gives 7. AIS
      patients appear less mesomorphic with a mean value of 1,208 +/- 1.03 than the
      control group with a mean value of 1,923 +/- 0.89 (Student "t" test: 6,149, p <
      0.0001). Based on these results, a relationship between morphological somatotypes
      and the presence of AIS appears possible. A more elaborate prospective study will
      be needed to support this hypothesis.

PMID- 8561433
TI  - [Responses of ligamentous fibroblasts to mechanical stimulation].
AB  - Mechanical stimulation, as provided by physiotherapy or controlled motion is
      essentially the only factor able to improve anterior cruciate ligament (ACL)
      healing. We investigate the cellular effects of such stimulus. Two types of
      stimulations are applied on canine ACL fibroblasts: repetitive stretch of an
      elastomeric adhesion substrate and a laminar flow of culture media over the
      culture surface. Cell orientation, proliferation rate, synthesis and type of
      collagen as well as proteoglycans (PG) synthesis and hydrodynamic characteristics
      have been studied. According to our results, the fibroblasts tend to align
      perpendicularly to the deformation axis of their substrate, and along a laminar
      flow. The shear stress induced by the laminar flow does not modify significantly
      proliferation rate nor extracellular matrix synthesis. Substrate stretching
      however, increases proliferation rate, collagen synthesis, mostly type III, and
      PG synthesis, principally of small sizes. The characteristics of fibroblasts
      submitted to repeated deformation match those of fibroblasts from ligament scar
      tissues. Their orientation perpendicular to substratum deformation differs from
      the one usually encountered in the undamaged tissue: aligned on the ligament
      axis.

PMID- 8561434
TI  - [Functional study of Swanson's metacarpophalangeal arthroplasties in rheumatoid
      arthritis].
AB  - To validate a functional hand evaluation and to obtain an historical control
      group in a project of metacarpophalangeal total joint prosthesis, we reviewed our
      experience over a ten year period of Swanson's metacarpophalangeal joint
      arthroplasty in rheumatoid arthritis. Forty-nine implants in fourteen rheumatoid
      arthritis patients were reviewed clinically, radiologically and evaluated by the
      Arthritic Hand Function Test. The mean follow up was 4.5 years. All patients were
      ready to repeat the experience except one. The mean metacarpophalangeal joint
      range of motion was 37 degrees (18 degrees to 55 degrees) with a mean of 7
      degrees ulnar deviation. Although their functional performance was 50% of normal,
      all patients completed the test. The strength was generally greater on the
      operated side. The low complication rate (6% fracture rate) with the successful
      functional outcome of Swanson's metacarpophalangeal joint arthroplasty in
      rheumatoid arthritis will be the gold standard for any new implant to develop.

PMID- 8561435
TI  - [Arrhythmogenic right ventricle: dysplasia or cardiomyopathy? Value of left
      ventricle ejection fraction].
AB  - The left ventricular ejection fraction (LVEF) of 76 patients suffering from
      arrhythmogenic dysplasia or cardiomyopathy of the right ventricle (ventricular
      tachycardia associated with structural abnormalities of the right ventricle)
      demonstrated two subgroups situated above and below 45%. Values of LVEF less than
      45% were similar to those of a control population of 6 cases of idiopathic
      dilated cardiomyopathy with ventricular tachycardia of left ventricular origin (p
      = 0.2). These patients also have the same unfavourable long-term prognosis.
      Histological data obtained from four cases belonging to the group of patients
      with dysplasia or cardiomyopathy of the right ventricle with a low ejection
      fraction demonstrated the presence of signs of myocarditis involving both
      ventricles. This suggests that these patients may suffer from an infectious
      phenomenon superimposed on a specific histological substrate, which may lead to
      deterioration of their myocardial function. These results are in line with those
      of the literature. The term arrhythmogenic cardiomyopathy of the right ventricle
      should therefore be reserved to the subgroup of patients with an LVEF less than
      45%. Finally, arrhythmogenic cardiomyopathy of the right ventricle appears to be
      a complication of dysplasia following the development of a myocarditic
      phenomenon. This may explain the wide range of clinical forms observed in
      patients with ventricular tachycardia of right ventricular origin associated with
      structural abnormalities of the right ventricle.

PMID- 8561436
TI  - [Multidimensional transesophageal echocardiography in the determination of the
      orificial surface of aortic stenoses in adults. Apropos of 85 cases].
AB  - The objective of this study was to assess the validity of multidimensional
      transoesophageal echocardiography (TOE) in the determination of the orificial
      surface area of aortic stenosis (AS) in 85 patients, using as a reference the
      surface area calculated on transthoracic ultrasonography (TTU) by applying the
      continuity principle (n = 75) and/or by haemodynamic studies using Gorlin's
      formula (n = 40). Planimetry was able to be performed in 78 of the 85 patients
      (92%). Planimetry was impossible in 7 patients with massive calcification of the
      aortic orifice (n = 5) or posterior valve (n = 2). The mean value of the selected
      angle was 45 +/- 13 degrees (0 to 78 degrees). An excellent correlation was
      observed between aortic surface area (ASA) measured by multidimensional TOE and
      TTU (r = 0.94; y = 0.90x +/- 0.10; SEE = 0.10 cm2; p < 0.001). Similarly, the ASA
      on multidimensional TOE was also well correlated with the haemodynamic surface
      area (r = 0.90, y = 0.94x +/- 0.05; SEE = 0.09 cm2; p < 0.001). The correlations
      between multidimensional TOE and TTU measurements (n = 26; r = 0.96; y = 0.85 x
      +/- 0.11; SEE = 0.07 cm2; p < 0.001) and cardiac catheterization (n = 13; r =
      0.92; y = 0.77 x +/- 0.7; SEE = 0.09 cm2; p < 0.001) remained satisfactory in
      patients with associated aortic incompetence. Multidimensional TOE identifies
      cases of AS with an ASA on TOE or haemodynamic studies less than or equal to 0.75
      cm2 with sensitivities of 93% and 92%, respectively, and a specificity of 100%.
      Overall, multidimensional TOE allows a precise and reliable evaluation of ASA in
      the great majority of cases of AS.

PMID- 8561437
TI  - [Bacterial endocarditis in Morocco].
AB  - This retrospective study was based on 157 cases of infectious endocarditis
      observed in the Cardiology department of Ibn Rochd Hospital in Casablanca between
      January 1983 and December 1994. The mean age of the patients was 27.5 years (11
      to 65 years) with a male predominance (62.8%). Infectious endocarditis was
      secondary to rheumatic valvular heart disease in 63.% of patients and was primary
      in 29.9% of cases. Mitral or mitro-aortic valve involvement was clearly
      predominant. A portal of entry of the infection was identified in 63% of
      patients. It was dental in 64% of cases. Blood cultures were positive in 42% of
      cases with a predominance of unclassifiable Streptococci (37.8%) and coagulase
      negative Staphylococci (25.7% of cases). Echocardiography was very useful,
      particularly in the presence of negative blood cultures. It demonstrated specific
      lesions of infectious endocarditis in 73.2% of cases and revealed very large,
      mobile vegetations in every case complicated by systemic embolism. The clinical
      course was complicated by heart failure (47.8%), renal failure (14.6%) or
      neurological lesions (11.5%). The global mortality was 28.7%, related to
      refractory heart failure in most cases.

PMID- 8561438
TI  - [Malignant non-Hodgkin lymphoma of cardiac localization. Apropos of a case].
AB  - Malignant non-Hodgkin's lymphomas are rare in the absence of human
      immunodeficiency virus infection and it is exceptional for a cardiac site to be
      the prominent feature. In our case, the malignant lymphoma was revealed by
      pericardial effusion in a context of alteration of the general state.
      Echocardiography revealed a heterogeneous mass in the right atrium and an
      abundant circumferential pericardial effusion. Thoracic computed tomography
      allowed local staging and magnetic resonance imaging (MRI) allowed a better
      definition, than CT scan, of the extension of the tumour into the various cardiac
      structures. The histological diagnosis was established on biopsy of a mediastinal
      lymph node. The patient died 7 months after the diagnosis, despite chemotherapy.
      The authors emphasize the contribution of echocardiography in the diagnosis of
      cardiac tumours, computed tomography in local staging, and MRI in the analysis of
      the various cardiac structures.

PMID- 8561439
TI  - [Restenosis: physiopathology, treatments and prevention].
AB  - Despite fifteen years of extensive research, we still do not know how to predict
      or prevent restenosis. Angioplasty induces lesions in the intima, media and
      sometimes adventitia, resulting in a cicatricial process comprising proliferation
      and migration of smooth muscle cells towards the intima and secretion of
      extracellular matrix, leading to the formation of a neointima. Since angioplasty
      is associated with the simultaneous development of neointimal hyperplasia and
      restenosis, a cause and a effect relationship has therefore been proposed between
      neointimal hyperplasia and restenosis. All the restenosis prevention strategies
      based on inhibition of smooth muscle cell proliferation, which successfully
      limited restenosis in animal models have failed in man, due to the hazardous
      extrapolations from experimental models which are very different from the
      atheromatous lesions observed in man, rather than to the use of animal models in
      general. It is reasonable to wonder whether we have not selected the wrong
      target: is smooth muscle cell proliferation really responsible for restenosis?
      Experimental results supported by histological and ultrasonographic data in man,
      show that the cicatricial process which induces restenosis consists of
      constrictive remodelling, which decreases the perimeter of the external elastic
      lamina and the lumen. The use of stents appears to be the primary strategy
      designed to limit restenosis and prevent constrictive remodelling in man, even if
      it stimulates neointimal hyperplasia. Progress in the understanding of the
      mechanisms of postangioplasty remodelling open new perspectives in the prevention
      of restenosis.

PMID- 8561440
TI  - [Effects of thrombolysis on platelets and coagulation].
AB  - Rupture of an atherosclerotic plaque is often the trigger of the clotting
      process, via the activation of platelets which immediately adhere, aggregate and
      initiate coagulation on their surface. The final step of platelet aggregation
      involves membrane glycoprotein IIB-IIIA which has become available. Antibodies
      directed against this membrane receptor are currently under evaluation. They
      possess definite antithrombotic properties. Complex interactions between
      thrombolysis, leading to generation of plasmin, and platelet functions have been
      identified. Depending on its concentration and possibly successively, and
      according to in vitro experimental conditions, plasmin may be a platelet
      proaggregant or antiaggregant. Correlations have also been recently demonstrated
      between thrombolytic activity and coagulation, as, paradoxically, it has been
      shown that plasmin, the final step of thrombolysis, activates the intrinsic
      pathway of coagulation, predisposing to the formation of thrombin. This
      activation is involved in the efficacy of heparin therapy following intravenous
      thrombolysis during the acute phase of myocardial infarction. This paradoxical
      action of thrombolysis could also play a role in reocclusions after effective
      thrombolysis during the acute phase of myocardial infarction. A better
      understanding of the thrombolysis process and its interactions with platelets and
      coagulation is important in order to improve the results of this treatment, which
      are correlated with patient survival.

PMID- 8561441
TI  - [Correlation between the persistence of ST elevation and left ventricular
      aneurysm in the post-infarction period].
AB  - The objective of this study was to verify whether the persistence of ST elevation
      on ECG after myocardial infarction was well correlated with the presence of left
      ventricular aneurysm. This study concerns 30 male patients with a mean age of 46
      +/- 7.6 years, with ST elevation of more than 1 mm on ECG, at least 15 days after
      the presumed onset of myocardial infarction. All patients were investigated by
      echocardiography and cardiac catheterization. ST elevation was recorded in the
      ECG leads corresponding to the site of necrosis. 2D echocardiography identified
      21 cases (70%) of left ventricular aneurysm and cardiac catheterization revealed
      26 cases (86%). The electrical site of ST elevation was correlated with the site
      of the aneurysm. In conclusion, the persistence of ST elevation on the ECG more
      than 15 days after the onset of myocardial infarction has a good predictive value
      for the presence of left ventricular aneurysm, which can only be confirmed by
      cardiac catheterization.

PMID- 8561442
TI  - [Comparative study of verapamil LI 120 mg 3 times a day and verapamil LP 120 mg
      twice a day in stable exertion-induced angina. A multicenter study].
AB  - A multicentre, open, crossover study in 27 patients with exertional angina
      compared the efficacy of verapamil LP 120 mg twice a day (VP LP 120) with that of
      verapamil LI 120 mg 3 times a day (VP LI 120) by means of stress tests. The study
      procedure was as follows: 7-day selection period during which the patient
      received placebo, and two 21-day treatment periods by VP LI 120 or VP LP 120
      according to the crossover principle. At the end of each treatment phase, a
      stress test was performed at the trough serum concentration for each substance.
      VP LP 120 mg and VP LI 120 mg both improved exercise capacity compared to
      placebo. Comparison of VP LP 120 and VP LI 120 did not reveal any significant
      difference for stress test parameters (total duration of effort: 12 +/- 3.2 min
      with placebo, 13.3 +/- 3.7 min for the VP LI phase, 13.9 +/- 3.2 min for the VP
      LP phase; % FMT reached: 87.2% +/- 7.2 for VP LI, 89% +/- 7.3 for VP LP; time to
      onset of significant ST depression: 10 min +/- 2.9 for VP LI, 11 min 3.6 for VP
      LP). The efficacy of VP LP 120 in exertional angina is therefore identical to
      that of VP LI 120, despite a reduction of the total dose and serum levels.

PMID- 8561443
TI  - [Comparison of the antispastic effect of Bi-Tildiem 120 mg and Tildiem 60mg].
AB  - Diltiazem (Tildiem 60 mg) is a calcium channel blocker with demonstrated efficacy
      and safety in the treatment of stable angina pectoris and spastic angina. The
      sustained release formulation of diltiazem, allowing two daily doses (Bi-Tildiem
      120 mg), is already marketed in France for the treatment of stable angina. It was
      therefore interesting to evaluate the efficacy and safety of this form,
      administered in two daily doses, in coronary spasm, versus the classical
      formulation, Tildiem 60 mg, given at the same daily dose, i.e. 240 mg, in three
      divided doses per day. We conducted a single-centre, randomized, double-blind,
      cross-over clinical study in twelve patients, eleven men and one woman, between
      the ages of 42 and 70 years, presenting with angina and normal coronary arteries
      and spasm documented by a positive methylergonovine (Methergin) test. They were
      divided into two groups of six patients receiving either Tildiem followed by Bi
      Tildiem, or Bi-Tildiem followed by Tildiem. The characteristics of the two groups
      were comparable at the time of the selection visit. The methylergonovine test,
      used to assess the efficacy of the two treatments, was improved by Tildiem and Bi
      Tildiem compared to the placebo test (p = 0.001 and 0.002), without any
      significant difference between Tildiem and Bi-Tildiem: an improvement was
      obtained in 11/12 and 10/12 patients, respectively. No deterioration of the test
      was observed with Tildiem or Bi-Tildiem compared to placebo. The coronary
      symptoms and blood diltiazem levels were similar with Tildiem and Bi-Tildiem. The
      results confirmed the safety of Bi-Tildiem. A single adverse effect was
      attributed to treatment: an episode of mild insomnia. No serious adverse effect
      were observed and none of the patients discontinued the study. The efficacy and
      safety of Tildiem and Bi-Tildiem are comparable in the treatment of spastic
      angina.

PMID- 8561444
TI  - [Prevention of coronary disease in clinical practice. Recommendations of the Task
      Force of the European Society of Cardiology, European Atherosclerosis Society and
      European Society of Hypertension].

PMID- 8561445
TI  - [Deep vertical facelift. Development of a concept].
AB  - An optimal result with minimal surgery is expected by our patients. The concept
      of deep layer rhytidectomy is based on the simultaneous vertical "en bloc"
      elevation of skin, fat and the SMAS. The extended undermining of this facial flap
      is so effective that it allows a simplification of the lifting reducing the
      subcutaneous undermining to one fourth of what is achieved in a standard face
      lift, eliminating the anterior platysmaraphy. Length of procedure is divided by
      two. Three hundred forty patients have undergone surgery according to this
      simplified procedure and we will show how "our" technique becomes soft.

PMID- 8561446
TI  - [An unusual complication of cervicofacial lift: paralysis of the external branch
      of the accessory spinal nerve].
AB  - Paralysis of the lateral branch of the accessory nerve is an extremely rare
      lesion during cervico-facial facelift. Based on 3 detailed and published personal
      cases observed over a period of 15 years, the authors review the literature,
      revealing a total of 9 cases over a period of 30 years, but other cases have
      probably not been published. Their review reveals the following points. This is
      an exceptional lesion. However, the nerve can be damaged as it emerges from the
      posterior border of the sternocleidomastoid muscle during slightly deep
      dissection and the electrical scalpel must be used cautiously. Even, partial
      paralysis of the trapezius muscle induces pain and considerable functional
      impairment with partial permanent disability. The natural history of this
      paralysis is very long and may be followed by regression after several years.
      Although there is an obvious cause-and-effect relationship between the operation
      and accessory nerve paralysis, it is always difficult to attribute this lesion to
      a possible surgical error, as the exact mechanism of the nerve lesion remain
      hypothetical and once again raises the problem of therapeutic risk.

PMID- 8561447
TI  - [Results of the use of parietal bone as bone graft donor site in facial
      reconstruction. Apropos of 71 cases].
AB  - The embryologic origin of the parietal bone is membranous bone. Experimentally,
      membranous bone grafts, maintain its original size, structure with good osteo
      integration contrary to endochondral bone autografted (ilium, rib or tibia). The
      morbidity of skull bone grafts is much less than other donor site of bone. In our
      study, between 1988 and 1992, autogenous split calvarial bone grafts were used in
      maxillo-facial reconstruction of seventy-one patients. We observed no major
      complication. Patient followup has been from 2 to 6 years and results are better
      than endochondral grafts (iliac crest, ribs, tibia). Parietal grafts bone have
      been used in the following case: nasal reconstruction, rehabilitation of defects
      in the floor of the orbit, maxilla grafts, correction of frontal depression and
      mandibular reconstruction.

PMID- 8561448
TI  - [Mandibular reconstruction in oncology: discussion of indications].
AB  - The aim of the study was to assess the results of segmental mandibular resections
      and the validity of mandibular reconstructions. The medical records of 95
      patients treated between January 1, 1987 and December 31, 1992 were reviewed.
      There were 82 (86%) carcinomas, 9 ameloblastomas and 4 sarcomas. Among the 82
      patients treated for carcinoma, the overall 2- and 5-year survival rates were 70%
      and 33% respectively. The functional results evaluated one year after surgery
      showed no significant difference according to the reconstruction procedure:
      myocutaneous flap, osteomyocutaneous flap, titanium mandibular reconstruction
      plate or microsurgical transfer. The most important factor in functional
      rehabilitation is the amount of soft tissue resected. In head and neck oncology,
      aggressive surgical reconstruction of the mandible must only be used in patients
      with good general status and fair survival probability.

PMID- 8561449
TI  - [Maxillofacial prosthesis fixed on endosseous implants. Apropos of 15 cases].
AB  - In the light of 15 cases of craniofacial defects due to trauma of carcinomas, the
      authors propose a new approach of the indications for craniofacial prostheses.
      Progress in materials (silicons) and treatments of maxillo-facial defects
      (titanium implants) have renewed the interest in maxillo-facial prostheses in
      maxillo-facial surgery. The advantages and disadvantages of classical methods of
      prosthesis fixation (on glasses or adhesives) and modern techniques of extra-oral
      implants (Swedish) are cause of the recent interest for prostheses in plastic
      surgery. New implants (German) and easier techniques induce a growing interest
      for extra-oral implants.

PMID- 8561450
TI  - Total auricular reconstruction with a three-dimensional costal cartilage
      framework.
AB  - Microtia (hypoplasia of the auricle) is known to result from incomplete
      development of the auricle during embryonic development so that the size and
      shape of the deformity vary from case to case. Total auricular reconstruction for
      microtia is dependent on the degree of hypoplasia in comparison to that of the
      normal auricle on which the specific reconstruction method is based. I have
      classified microtia into 3 major types: 1) The lobule type. 2) The concha type,
      and 3) The small concha type which has been previously described [32]. Regardless
      of the size and shape of the deformity, the ultimate goal of total reconstruction
      of the auricle consists of construction of an auricle with an appearance as close
      as possible to that of a normal auricle. With this objective in mind, total
      reconstruction of the article is a science and not just a form of art as
      frequently considered. If it is only an art, the constructed auricle is greatly
      influenced by the artist's individuality and by the observer's. Thus, as a
      reconstructive plastic surgeon, the final outcome or result of total
      reconstruction of the auricle is that the constructed auricle should resemble as
      closely as possible the normal auricle, regardless of the observer and without
      any personal influence of the surgeon. I therefore consider total reconstruction
      of the auricle to be a field of science attained by numerous refinements and
      modifications in the procedures and techniques [33-36] and not just a simple form
      of art. The auricle constitutes only a small portion of the total body surface
      area, but it is probably one of the most complicated and/or sophisticated
      morphological structures of the body. It is necessary to fully understand the
      three-dimensional (3-D) morphological properties of the auricle and to pursue the
      ultimate goal of reconstructing an everlasting auricle as to the normal auricle.
      In other words, the constructed close as possible auricle must not be a
      sculptured object or structure, but is a living structure. A healthy constructed
      auricle is lasting and alive. Follow-up studies must be performed with strict
      standards and evaluation criteria in order to determine whether or not a
      reconstructed auricle is healthy.

PMID- 8561451
TI  - [Does the choice of mammoplasty pedicle influence the shape of reduced the
      reduced-sized breast?].
AB  - Thirty seven patients with breast hypertrophy were restrospectively reviewed with
      a mean follow-up of 2 years. Reduction mammoplasty was performed with 3 different
      pedicles (superior, inferior and both) involving a glandular resection of a least
      500 g on each side in all cases. The results were evaluated according to both
      objective and subjective criteria. The choice of pedicle had a considerable
      influence on the results. The vertical limb usually increased with time (months),
      although its intraoperative length was 5 cm. The increasing length of the
      vertical limb varies according to the type of pedicle chosen. The mean length
      increase was 1.52 cm; 4.18 cm; 4.15 cm for superior, inferior, and both pedicles
      respectively. The different increase was statistically significant (p < 0.001)
      when the technic involving a superior pedicle was compared to a technic involving
      an inferior pedicle. No statistically significant difference was observed between
      technics using the inferior and both pedicles. A superior pedicle technic entails
      the lowest increase of the vertical limb length which in turns leads to better
      long-term cosmetic results.

PMID- 8561452
TI  - [A study of the influence of sutures and tension on skin cicatrization in loss of
      substance in 18 minipigs].
AB  - This study concerned the evaluation of wound healing after extensive skin
      resections in 18 minipigs, sutured with: continuous intradermal Polyglactin 910
      suture or Polyamide, an interrupted intradermal sutures using the same resorbable
      suture material. Three equivalent groups were studied: 0, 3 and 6 cm skin
      resections were studied after using a dynamometer to record the tension necessary
      to join the wound margins. Results were evaluated 1 month later by light and
      electron microscopy, and were statistically correlated by Pearson's test. The
      wound tension was correlated with skin resection (r = 0.97, p < 10-4). The scar
      width was exponentially correlated with tension (r = 0.70, p < 10-3); the fibrous
      and cellular appearances increased with the skin resection. The absence of any
      significant statistical results prevents any conclusion concerning the
      superiority of one suture material or suture technique, but the group with no
      resection led to homogenous results, regardless of the suture technique, or
      suture material used. 3 and 6 cm resection the groups led to unpredictable and
      various results. Granulous reactions were observed in 7 out of 12 cases with
      resorbable suture, and only 1 of the 8 cases with non resorbable suture, but
      these results are not significant.

PMID- 8561453
TI  - [Unusual use of a tissue expander].
AB  - Postpneumonectomy syndrome is a rare but serious complication. Mediastinal shift
      leads to compression of the remaining main bronchus. Repositioning of the
      mediastinum in the midline allows partial or total recovery. To maintain
      mediastinal position, the pneumonectomy space must be filled by a tissue
      expander.

PMID- 8561454
TI  - [Xeroderma pigmentosum and Gunther disease].

PMID- 8561455
TI  - The road to Yellowstone--and beyond.
AB  - This memoir describes the professional life and times of Thomas D. Brock, with an
      emphasis on those aspects of his career relating to research in microbial
      ecology, and how this work led to field research in Yellowstone. The first
      discovery of extremely thermophilic bacteria is described, followed by a
      discussion of some of the consequences of this discovery for biotechnology and
      microbiology. Also covered briefly in this memoir are Brock's activities in
      textbook writing, publishing, computers, and the history of science.

PMID- 8561456
TI  - The structure and replication of kinetoplast DNA.
AB  - The mitochondrial DNA of trypanosomatid protozoa, termed kinetoplast DNA (kDNA),
      is unique in its structure, function, and mode of replication. kDNA is a massive
      network, composed of thousands of topologically interlocked DNA circles, which
      resembles the chain mail of medieval armor. Each cell contains one network
      condensed into a disk-shaped structure within the matrix of its single
      mitochondrion. The kDNA circles are of two types, maxicircles present in a few
      dozen copies and minicircles present in several thousand copies. The maxicircles,
      which encode ribosomal RNAs and a few mitochondrial proteins, are similar in
      structure and genetic function to the mitochondrial DNA of other eukaryotes. Many
      maxicircle transcripts undergo editing, a remarkable process involving the
      insertion or deletion of uridine residues at specific sites. The minicircles
      encode small guide RNAs that control the specificity of editing. During kDNA
      replication, covalently closed minicircles are released from the network by a
      topoisomerase II. The free minicircles replicate as theta-structures within one
      of two complexes of replication proteins that are positioned on opposite sides of
      the kinetoplast disk. The progeny minicircles, which contain nicks or gaps, are
      attached to the network periphery. Maxicircles also replicate as theta
      structures, but they remain linked to the network. As replication proceeds, the
      number of minicircles and maxicircles increases. When the network has doubled in
      size, all of the minicircle nicks and gaps are repaired, and the network splits
      in two. The two progeny networks then segregate into the daughter cells.

PMID- 8561457
TI  - How Salmonella survive against the odds.
AB  - The enteric pathogen Salmonella typhimurium faces daunting odds during its
      voyages in the natural environment and through an infected host. It must manage
      stresses ranging from feast to famine, acid to base, and high to low osmolarity,
      among others, as well as counter various types of oxidative stress and a variety
      of antimicrobial peptides. The defenses used to survive these encounters can be
      specific or can provide cross protection to a variety of hostile conditions. Once
      inside a host, Salmonella spp. escape the extracellular environment and thus
      humoral immunity by invading professional and nonprofessional phagocytes in which
      a new set of challenges await. Some of these stresses are similar to those
      encountered in the natural environment (e.g. acid, starvation) but the bacterial
      response is complicated by the simultaneous occurrence of multiple stresses. S.
      typhimurium appears to sense various in vivo cues and responds by seducing the
      host signal-transduction pathways that are required to phagocytize the bacterial
      cell. The pathogen then calls upon components of its stress-response arsenal to
      survive the intracellular environment. These survival strategies enable the
      organism to persist in nature, where conditions are usually suboptimal, and equip
      the bacterium with pathogenic properties that, if successful, will provide it
      with a very rich and stress-free growth environment, a dead host.

PMID- 8561458
TI  - The mechanisms of Trypanosoma cruzi invasion of mammalian cells.
AB  - The protozoan parasite Trypanosoma cruzi must enter cells of its vertebrate host
      in order to replicate. Once this is accomplished, the infective trypomastigotes
      can invade many different cell types from several host species. This observation
      is in agreement with the parasite's wide natural host range. Studies performed
      with cultured mammalian cells in vitro have shown that T. cruzi invasion is an
      unusual process, distinct from phagocytosis, that depends on parasite energy and
      on negatively charged surface molecules of the host cell. Several surface
      glycoproteins and mucin-like molecules of trypomastigotes have been implicated,
      mainly by inhibition studies with antibodies, in interactions with host cells.
      Recently, several of the trypomastigote surface glycoproteins were shown to be
      related members of a large family that includes the T. cruzi trans-sialidase. The
      mucin-like molecules are beginning to emerge as a separate family of threonine
      rich, O-glycosylated molecules that function as acceptors of sialic acid in the
      infective stages. Several lines of evidence suggest that parasite surface
      molecules mediate binding to host cells, whereas invasion of nonphagocytic cells
      involves recruitment of host-cell lysosomes, an unusual event apparently
      triggered by signal transduction.

PMID- 8561459
TI  - Polyketide synthase gene manipulation: a structure-function approach in
      engineering novel antibiotics.
AB  - Polyketides are produced primarily in microorganisms through a specialized
      metabolism that is a variation of fatty acid biosynthesis. A strong sequence and
      mechanistic similarity among many of the fatty acid and polyketide synthase
      enzymes has led to two paradigms for explaining polyketide biochemistry. In one,
      polyketides are formed by enzyme complexes consisting of four to seven
      monofunctional proteins in which the beta-carbonyl groups of the intermediates
      resulting from the condensation of acetate residues are largely not reduced and
      cyclization of the intermediates typically produces aromatic compounds. The
      intermediates in the other model are formed by multifunctional enzymes in which
      each of the initial condensation products is processed through reduction;
      reduction and dehydration; or reduction, dehydration, and further reduction
      cycles to produce highly reduced compounds from acetate, propionate, and butyrate
      residues. Expression of the genes encoding each type of polyketide synthase, or
      their mutant forms, has provided much information about the underlying
      biochemistry and, in some cases, resulted in the formation of novel natural
      products.

PMID- 8561460
TI  - Nonopsonic phagocytosis of microorganisms.
AB  - Nonopsonic phagocytosis mediated by phagocyte receptors that recognize
      corresponding adhesins on microbial surfaces has attracted increasing interest as
      a potential host defense mechanism against extracellular pathogens and as a means
      of survival in the host for intracellular pathogens. Three types of nonopsonic
      phagocytosis involving carbohydrate-protein interactions (also termed
      lectinophagocytosis), protein-protein interactions, and hydrophobic interactions
      are discussed. A prominent receptor on phagocytic cells involved in recognizing
      pathogens belongs to the CD11/CD18 integrins. It mediates both opsonophagocytosis
      and nonopsonic phagocytosis and exhibits multiple specificity for different
      microbial adhesins. In other cases, similar specificity toward a microbial ligand
      (e.g. the Klebsiella pneumoniae capsule) is shared by dual molecules, one of
      which (e.g. the mannose-binding protein in serum) mediates opsonophagocytosis and
      the other (e.g. the macrophage mannose receptor) mediates nonopsonic phagocytosis
      of the microorganisms. In addition, we discuss how nonopsonic phagocytosis can
      trigger the phagocytes to release inflammatory agents and cause tissue injury.
      Further studies of the molecular mechanisms of nonopsonic phagocytosis, in
      particular those underlying the up-regulation of the phagocytic receptors by
      various agents, should lead to the development of new approaches for the
      prevention of infectious diseases.

PMID- 8561461
TI  - Peptides as weapons against microorganisms in the chemical defense system of
      vertebrates.
AB  - The innate immunity of vertebrates to microbial invasion is arbitrated by a
      network of host-defense mechanisms involving both the long-lasting highly
      specific responses of the cell-mediated immune system and a nonspecific chemical
      defense system based on a series of broad-spectrum antimicrobial peptides that
      are analogous to those found in insects. Vertebrate antibiotic peptides secreted
      by nonlymphoid cells of the mucosal surfaces of the respiratory and
      gastrointestinal tracts as well as by the granular glands of the skin reportedly
      cause the lysis of numerous pathogenic microorganisms, including viruses, gram
      positive and gram-negative bacteria, protozoa, yeasts, and fungi, as well as of
      cancer cells. Antimicrobial peptides isolated from vertebrates have three
      characteristic properties: They are relatively small (20-46 amino acid residues),
      basic (lysine- or arginine-rich), and amphipathic. Although these peptides differ
      widely in length and amino acid sequences, they may be grouped in four broad
      families based on characteristic structural features. Although the precise
      mechanism of action of these peptides remains to be defined, their microbicidal
      effect very likely results from their capacity to form channels or pores within
      the microbial membrane in order to permeate the cell and impair its ability to
      carry out anabolic processes. This secondary, chemical immune system provides
      vertebrates with a repertoire of small peptides that are promptly synthesized
      upon induction, easily stored in large amounts, and readily available for
      antimicrobial warfare.

PMID- 8561462
TI  - Mechanisms for the prevention of damage to DNA in spores of Bacillus species.
AB  - The DNA in dormant spores of Bacillus subtilis as well as other Bacillus species
      is extremely well protected against damage resulting from treatments such as
      desiccation, heat, oxidizing agents, and UV and gamma radiation. This high degree
      of DNA protection is a major factor in the survival of spores of these species,
      not only when subjected to the treatments noted above, but also when incubated
      under common environmental conditions for many years. Factors that play major
      roles in overall spore resistance include the low permeability of spores to toxic
      chemicals and the decreased spore-core water content. However, although decreased
      spore permeability and water content appear to at least partially protect spore
      DNA from oxidative damage, these factors seem to play little or no role in
      protecting spore DNA from heat damage. The major factor preventing damage to
      spore DNA is the saturation of this DNA with a novel group of small, acid-soluble
      proteins of the alpha/beta-type whose binding greatly alters DNA's chemical and
      enzymatic reactivity as well as its UV photochemistry. Binding of these proteins
      is also a key factor in spore DNA resistance to desiccation, heat, oxidizing
      agents, and UV radiation.

PMID- 8561463
TI  - CO dehydrogenase.
AB  - Structurally and functionally diverse CO dehydrogenases are key components of
      various energy-yielding pathways in aerobic and anaerobic microbes from the
      Bacteria and Archaea domains. Aerobic microbes utilize Mo-Fe-flavin CO
      dehydrogenases to oxidize CO in respiratory pathways. Phototrophic anaerobes grow
      by converting CO to H2, a process initiating with a CO dehydrogenase that
      contains nickel and iron-sulfur centers. Acetate-producing anaerobes employ a
      nickel/iron-sulfur CO dehydrogenase to synthesize acetyl-CoA from a methyl group,
      CO, and CoA. A similar enzyme is responsible for the cleavage of acetyl-CoA by
      anaerobic Archaea that obtain energy by fermenting acetate to CH4 and CO2.
      Acetotrophic sulfate reducers from the Bacteria and Archaea also utilize CO
      dehydrogenase to cleave acetyl-CoA yielding methyl and carbonyl groups. These
      microbes obtain energy for growth via a respiratory pathway in which the methyl
      and carbonyl groups are oxidized to CO2, and sulfate is reduced to sulfide.

PMID- 8561464
TI  - Nitrogenase structure and function: a biochemical-genetic perspective.
AB  - Biological nitrogen fixation is catalyzed by nitrogenase, an enzyme composed of
      two component proteins called the Fe protein and the MoFe protein. During
      catalysis, electrons are delivered one at a time from the Fe protein to the MoFe
      protein in a process involving component-protein association and dissociation and
      hydrolysis of at least two MgATP for each electron transfer. The Fe protein
      contains the sites for MgATP binding and hydrolysis, whereas the site for
      substrate binding and reduction is located on the MoFe protein. Among the
      important aspects of nitrogenase enzymology discussed here are (a) the structures
      of the metal centers that participate in electron transfer, (b) the organization
      of the metalloclusters within the polypeptides and their contributions to
      substrate binding and electron transfer, (c) the nature of the dynamic
      interactions between the two component proteins that lead to nucleotide
      hydrolysis and intermolecular electron transfer, (d) the mechanism by which the
      multiple electrons necessary for substrate reduction are distributed within the
      MoFe protein, (e) the nature of the intramolecular electron path within the MoFe
      protein, and (f) where and how substrate and various inhibitors become bound to
      the substrate-reduction site. This chapter summarizes biochemical-genetic
      strategies used to address these questions and discussed them in the context of
      the recently proposed three-dimensional models for both the Fe protein and MoFe
      protein from Azotobacter vinelandii.

PMID- 8561465
TI  - Conjugative transposition.
AB  - Conjugative transposons are important determinants of antibiotic resistance,
      especially in gram-positive bacteria. They are remarkably promiscuous and can
      conjugate between bacteria belonging to different species and genera. Transposon
      promoted conjugation may be similar to F plasmid-promoted conjugation, as it
      appears that only one strand of the transposon DNA is transferred from donor to
      recipient. The recent determination of the entire nucleotide sequence of Tn916
      allowed us to make specific predictions about the possible function of different
      open reading frames and the position of a (hypothetical) origin of transfer. The
      mechanism of recombination during conjugative transposition differs from that of
      other transposons, as shown by the absence of a duplication of the target
      sequence upon integration. The current model for recombination postulates that
      staggered double-stranded cleavages occur at each end of the transposon. One DNA
      strand is cut six bases from the end of the transposon, and the other strand is
      cut immediately adjacent to the end. The ends of the excised transposon are then
      ligated to form a circular intermediate with a six-base heteroduplex. Staggered
      cleavages of the circular intermediate and the target DNA allow the transposon to
      insert into the target, where it is flanked by heteroduplex regions that are
      resolved by replication. All hosts examined contain preferential target sites:
      these are not specific sequences but apparently consist of bent DNA. The site
      specific recombinases encoded by conjugative transposons belong to the integrase
      family. Like phage lambda integrase, the integrase of Tn916 has two DNA-binding
      domains that recognize different sequences, one within the ends of the element
      and one that includes target DNA. The affinity of Tn916 integrase for target
      sites correlates with the frequency of integration into a particular site. The
      similarity between conjugative transposons and phage lambda is striking and
      suggests that both use the same mechanism of recombination. In lambda, however,
      recombining sites must be homologous. Homology may be necessary because of branch
      migration, which is thought to occur during recombination. In conjugative
      transposition, the recombining sites are nearly always different, and therefore
      branch migration probably does not occur. This review presents a speculative
      model for the alignment of the ends of Tn916 during excision that was adapted
      from one recently proposed for lambda.

PMID- 8561466
TI  - Cellulose degradation in anaerobic environments.
AB  - In anaerobic environments rich in decaying plant material, the decomposition of
      cellulose is brought about by complex communities of interacting microorganisms.
      Because the substrate, cellulose, is insoluble, bacterial and fungal degradation
      occurs exocellularly, either in association with the outer cell envelope layer or
      extracellularly. Products of cellulose hydrolysis are available as carbon and
      energy sources for other microbes that inhabit environments in which cellulose is
      biodegraded, and this availability forms the basis of many microbial interactions
      that occur in these environments. This review discusses interactions among
      members of cellulose-decomposing microbial communities in various environments.
      It considers cellulose decomposing communities in soils, sediments, and aquatic
      environments, as well as those that degrade cellulose in association with
      animals. These microbial communities contribute significantly to the cycling of
      carbon on a global scale.

PMID- 8561467
TI  - New mechanisms of drug resistance in parasitic protozoa.
AB  - The main line of defense now available against parasitic protozoa--which are
      responsible for major diseases of humans and domestic animals--is chemotherapy.
      This defense is being eroded by drug resistance and, with few new drugs in the
      pipeline, prevention and circumvention of resistance are medical and veterinary
      priorities. Although studies of resistance mechanisms in parasites have lagged
      behind similar studies in bacteria and cancer cells, the tools to tackle this
      problem are rapidly improving. Transformation with exogenous DNA is now possible
      with all major parasitic protozoa of humans. Hence, putative resistance genes can
      be tested in sensitive protozoa, allowing an unambiguous reconstruction of
      resistance mechanisms. Gene cloning, the polymerase chain reaction, and
      monoclonal antibodies against resistance-related proteins have made it possible
      to analyze potential resistance mechanisms in the few parasites that can be
      obtained from infected people. Hence, the prospect of applying new knowledge
      about resistance mechanisms to parasites in patients is good, even though today
      virtually all knowledge pertains to parasites selected for resistance in the
      laboratory. Resistance mechanisms highlighted in this review include: 1. Decrease
      of drug uptake because of the loss of a transporter required for uptake. This
      decrease contributes to resistance to arsenicals and diamidines in African
      trypanosomes. 2. The export of drugs from the parasite by P-glycoproteins and
      other traffic ATPases. This export could potentially be an important mechanism of
      resistance, as these proteins are richly represented in the few protozoa
      analyzed. There are indications that such transmembrane transporters can be
      involved in resistance to emetine in Entamoeba spp., to mefloquine in Plasmodium
      spp., and to antimonials in Leishmania spp. 3. The possible involvement of the P
      glycoprotein encoded by the Plasmodium falciparum pfmdr1 gene in chloroquine
      resistance. We present the available data that lead to the conclusion that
      overproduction of the wild-type version of this protein results in chloroquine
      hypersensitivity rather than resistance. 4. The involvement of the PgpA P
      glycoprotein of Leishmania spp. in low-level resistance to arsenite and
      antimonials. We raise the possibility that this protein transports glutathione
      conjugates of arsenite and antimonials rather than the compounds themselves. 5.
      Loss of drug activation as the main mechanism of metronidazole resistance in
      Trichomonas and Giardia spp. Recent evidence indicates that a decrease of the
      proximal cellular electron donor for metronidazole activation, ferredoxin, is the
      main cause of resistance in Trichomonas. 6. Resistance arising through alteration
      of drug targets. The amino acid substitutions in the dihydrofolate reductase
      thymidylate synthase of Plasmodium spp. are good examples of this
      mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8561468
TI  - Environmental virology: from detection of virus in sewage and water by isolation
      to identification by molecular biology--a trip of over 50 years.
AB  - Environmental virology began with efforts to detect poliovirus in sewage and
      water more than 50 years ago. Since that time, cell-culture methods useful for
      detection of enteroviruses have been replaced by molecular biology techniques for
      detection of pathogens (hepatitis A and E viruses, caliciviruses, rotaviruses,
      and astroviruses) that do not grow in cell culture or grow with great difficulty.
      Amplification of viral nucleic acid using the polymerase chain reaction (PCR) is
      the current preferred method. PCR or RT-PCR (to detect RNA viral genomes) is
      rapid, sensitive, specific, and quantitative. Method shortcomings include
      potential inhibition by substances in some environmental samples and an inability
      of test results to distinguish between infectious and noninfectious virus.
      Current questions involving use of PCR/RT-PCR tests for public health purposes
      include: What is the public health significance of a positive test, and should
      direct tests for viruses replace current public health-monitoring programs?

PMID- 8561469
TI  - How bacteria sense and swim.
AB  - Cells of Escherichia coli or Salmonella typhimurium can sense chemicals in their
      environment and respond by moving toward some and away from others. The ability
      to sense and swim requires the products of approximately 50 genes, about 10 for
      detecting and processing sensory cues and the rest for assembly and operation of
      the flagella. The function of each component in the chemosensory signaling
      pathway is well understood. Signaling is known to involve phosphorylation of a
      set of cytoplasmic proteins, but questions remain concerning the protein
      conformational changes and interactions that take place. Functions have been
      assigned to almost all of the approximately 40 flagellar proteins, and the
      sequence of events in flagellar assembly has been largely determined. Flagellar
      assembly depends on a specialized apparatus for exporting certain flagellar
      components to their appropriate locations. The structure and mechanism of this
      apparatus remain a mystery, as does the mechanism by which the flagellar motor
      generates torque.

PMID- 8561470
TI  - Biodegradation of nitroaromatic compounds.
AB  - Nitroaromatic compounds are released into the biosphere almost exclusively from
      anthropogenic sources. Some compounds are produced by incomplete combustion of
      fossil fuels; others are used as synthetic intermediates, dyes, pesticides, and
      explosives. Recent research revealed a number of microbial systems capable of
      transforming or biodegrading nitroaromatic compounds. Anaerobic bacteria can
      reduce the nitro group via nitroso and hydroxylamino intermediates to the
      corresponding amines. Isolates of Desulfovibrio spp. can use nitroaromatic
      compounds as their source of nitrogen. They can also reduce 2,4,6-trinitrotoluene
      to 2,4,6-triaminotoluene. Several strains of Clostridium can catalyze a similar
      reduction and also seem to be able to degrade the molecule to small aliphatic
      acids. Anaerobic systems have been demonstrated to destroy munitions and
      pesticides in soil. Fungi can extensively degrade or mineralize a variety of
      nitroaromatic compounds. For example, Phanerochaete chrysosporium mineralizes 2,4
      dinitrotoluene and 2,4,6-trinitrotoluene and shows promise as the basis for
      bioremediation strategies. The anaerobic bacteria and the fungi mentioned above
      mostly transform nitroaromatic compounds via fortuitous reactions. In contrast, a
      number of nitroaromatic compounds can serve as growth substrates for aerobic
      bacteria. Removal or productive metabolism of nitro groups can be accomplished by
      four different strategies. (a) Some bacteria can reduce the aromatic ring of
      dinitro and trinitro compounds by the addition of a hydride ion to form a hydride
      Meisenheimer complex, which subsequently rearomatizes with the elimination of
      nitrite. (b) Monooxygenase enzymes can add a single oxygen atom and eliminate the
      nitro group from nitrophenols. (c) Dioxygenase enzymes can insert two hydroxyl
      groups into the aromatic ring and precipitate the spontaneous elimination of the
      nitro group from a variety of nitroaromatic compounds. (d) Reduction of the nitro
      group to the corresponding hydroxylamine is the initial reaction in the
      productive metabolism of nitrobenzene, 4-nitrotoluene, and 4-nitrobenzoate. The
      hydroxylamines undergo enzyme-catalyzed rearrangements to hydroxylated compounds
      that are substrates for ring-fission reactions. Potential applications of the
      above reactions include not only the biodegradation of environmental
      contaminants, but also biocatalysis and synthesis of valuable organic molecules.

PMID- 8561471
TI  - Genetics, physiology, and evolutionary relationships of the genus Buchnera:
      intracellular symbionts of aphids.
AB  - Evolutionary studies suggest that 200-250 million years ago an aphid ancestor was
      infected with a free-living eubacterium. The latter became established within
      aphid cells. Host and endosymbiont (genus Buchnera) became interdependent and
      unable to survive without each other. The growth of Buchnera became integrated
      with that of the aphids, which acquired the endosymbionts from their mothers
      before birth. Speciation of host lineages was paralleled by divergence of
      associated endosymbiont lineages, resulting in parallel evolution of Buchnera and
      aphids. Present day Buchnera retains many of the properties of its free-living
      ancestor, containing genes for proteins involved in DNA replication,
      transcription, and translation, as well as chaperonins and proteins involved in
      secretion, energy-yielding metabolism, and amino acid biosynthesis. Some of these
      processes are also observed in isolated endosymbiont cells. Genetic and
      physiological studies indicate that Buchnera can synthesize methionine, cysteine,
      and tryptophan and supply these amino acids to the aphid host. In the case of
      some fast-growing species of aphids, the overproduction of tryptophan by Buchnera
      involves plasmid-amplification of the gene coding for anthranilate synthase, the
      first enzyme of the tryptophan biosynthetic pathway. These recent studies provide
      a beginning in our understanding of Buchnera and its role in the endosymbiosis
      with aphids.

PMID- 8561472
TI  - Biocatalytic syntheses of aromatics from D-glucose: renewable microbial sources
      of aromatic compounds.
AB  - Chemistry is moving into a new era in which renewable resources and starting
      materials such as D-glucose will likely be prominent features of industrial
      chemical manufacture. The keys to this progress are the design, development, and
      use of microbial biocatalysts. Aromatic biosynthesis serves as a paradigm for how
      biocatalysts can be manipulated to achieve the yield, rate, and purity criteria
      central to chemical manufacture. A disproportionate amount of the metabolic
      carbon flow of the biocatalyst must first be directed into the common pathway of
      aromatic amino acid biosynthesis. This review describes ways of achieving this
      goal through the traditional strategy of manipulating the catalytic activity of
      the first enzyme in the common pathway, as well as the amelioration of
      limitations in the in vivo availability of common-pathway enzyme substrates. The
      inability of individual enzymes to convert their substrate to product fast enough
      to avoid substrate accumulation further impedes carbon flow through the common
      pathway. This review also discusses identification and removal of these rate
      limiting enzymes. Finally, we examine the creation of heterologous biocatalysts
      and how biocatalysis could be integrated with traditional chemical
      transformations to expand the number of organic chemicals that can be synthesized
      from glucose.

PMID- 8561473
TI  - The regulation of methane oxidation in soil.
AB  - The atmospheric concentration of methane, a greenhouse gas, has more than doubled
      during the past 200 years. Consequently, identifying the factors influencing the
      flux of methane into the atmosphere is becoming increasingly important.
      Methanotrophs, microaerophilic organisms widespread in aerobic soils and
      sediments, oxidize methane to derive energy and carbon for biomass. In so doing,
      they play an important role in mitigating the flux of methane into the
      atmosphere. Several physico-chemical factors influence rates of methane oxidation
      in soil, including soil diffusivity; water potential; and levels of oxygen,
      methane, ammonium, nitrate, nitrite, and copper. Most of these factors exert
      their influence through interactions with methane monooxygenase (MMO), the enzyme
      that catalyzes the reaction converting methane to methanol, the first step in
      methane oxidation. Although biological factors such as competition and predation
      undoubtedly play a role in regulating the methanotroph population in soils, and
      thereby limit the amount of methane consumed by methanotrophs, the significance
      of these factors is unknown. Obtaining a better understanding of the ecology of
      methanotrophs will help elucidate the mechanisms that regulate soil methane
      oxidation.

PMID- 8561474
TI  - Discovery, biosynthesis, and mechanism of action of the zaragozic acids: potent
      inhibitors of squalene synthase.
AB  - The zaragozic acids (ZAs), a family of fungal metabolites containing a novel
      4,6,7-trihydroxy-2,8-dioxobicyclo[3.2.1]octane-3,4,5-tricarboxylic acid core,
      were discovered independently by two separate groups screening natural product
      sources to discover inhibitors of squalene synthase. This family of compounds all
      contain the same core but differ in their 1-alkyl and their 6-acyl side chains.
      Production of the ZAs is distributed over an extensive taxonomic range of
      Ascomycotina or their anamorphic states. The zaragozic acids are very potent
      inhibitors of squalene synthase that inhibit cholesterol synthesis and lower
      plasma cholesterol levels in primates. They also inhibit fungal ergosterol
      synthesis and are potent fungicidal compounds. The biosynthesis of the zaragozic
      acids appears to proceed through alkyl citrate intermediates and new members of
      the family have been produced through directed biosynthesis. These potent natural
      product based inhibitors of squalene synthase have potential to be developed
      either as cholesterol lowering agents and/or as antifungal agents.

PMID- 8561475
TI  - Prospects for new interventions in the treatment and prevention of mycobacterial
      disease.
AB  - Mycobacterium tuberculosis claims more lives each year than any other single
      human pathogen. Despite the availability of effective drugs, the incidence of
      tuberculosis is increasing in much of the developing world and has recently
      reemerged as a public health problem in industrialized countries. In the first
      section of this chapter, current understanding of the fundamental biology of
      mycobacterial infection is reviewed from the perspective of development of new
      tools for disease control. A second section describes strategies for
      identification of novel antimycobacterial agents, with particular emphasis on
      recent progress in defining biosynthetic pathways for unique mycobacterial cell
      wall components. The third section focuses on current approaches to the
      development of new vaccine candidates consisting of live attenuated bacteria or
      individual antigenic subunits.

PMID- 8561476
TI  - Development and application of herpes simplex virus vectors for human gene
      therapy.
AB  - Advances in understanding the molecular basis of human disease and the
      development of recombinant DNA methods is rapidly creating new means of disease
      diagnosis and treatment. Among the most revolutionary developments are
      technologies for transfer of therapeutic genes to the human body to treat both
      inherited and acquired disease. Gene therapy offers considerable promise for
      ameliorating otherwise intractable diseases such as immunopathological
      conditions, cancer, heart disease, and various metabolic and neurodegenerative
      syndromes. To fulfill this promise, more efficient and effective methods of gene
      delivery and appropriate gene expression must be developed. The lack of such
      techniques is currently the most significant impediment to the use of genetic
      therapy. Both viral and nonviral delivery systems are under development for
      specific gene-therapy applications. Herpes simplex virus (HSV) represents a novel
      vector system for gene delivery to the nervous system and other tissues. HSV is
      able to establish latency in nondividing neuronal cells in which genomes persist
      long-term but do not integrate or alter host-cell metabolism and that carry a
      promoter system uniquely capable of escaping repression that shuts off the
      expression of HSV-lytic genes during latency. This review examines efforts to
      create defective HSV vectors that are safe, noncytotoxic, and applicable to the
      treatment of cancer and diseases affecting peripheral nerves. Perhaps the most
      important use of HSV vectors will be for the treatment of neurodegenerative
      diseases of the brain, but additional studies are required to improve the design
      of promoters to ensure regulatable or effective levels of therapeutic gene
      expression.

PMID- 8561477
TI  - Microbial biofilms.
AB  - Direct observations have clearly shown that biofilm bacteria predominate,
      numerically and metabolically, in virtually all nutrient-sufficient ecosystems.
      Therefore, these sessile organisms predominate in most of the environmental,
      industrial, and medical problems and processes of interest to microbiologists. If
      biofilm bacteria were simply planktonic cells that had adhered to a surface, this
      revelation would be unimportant, but they are demonstrably and profoundly
      different. We first noted that biofilm cells are at least 500 times more
      resistant to antibacterial agents. Now we have discovered that adhesion triggers
      the expression of a sigma factor that derepresses a large number of genes so that
      biofilm cells are clearly phenotypically distinct from their planktonic
      counterparts. Each biofilm bacterium lives in a customized microniche in a
      complex microbial community that has primitive homeostasis, a primitive
      circulatory system, and metabolic cooperativity, and each of these sessile cells
      reacts to its special environment so that it differs fundamentally from a
      planktonic cell of the same species.

PMID- 8561478
TI  - Leucine-responsive regulatory protein: a global regulator of gene expression in
      E. coli.
AB  - The leucine-responsive regulatory protein (Lrp) regulates transcription of the
      many genes of the Lrp regulon, repressing some and activating others, some in
      response to L-leucine and some independent of it. The physiology and molecular
      biology of the regulon in Escherichia coli are summarized here. However, the high
      degree of conservation of the protein suggests that it has an important role in
      all enterobacteria. We suggest that this role is not only as a transcriptional
      regulator but also as a determinant of chromosome structure.

PMID- 8561479
TI  - Microbiology to 10,500 meters in the deep sea.
AB  - Microorganisms in the deep sea live at high pressures, low and high temperatures,
      and in darkness. These parameters and their food supply govern their lives. The
      study of these creatures gives us an opportunity to see how life processes work
      at some of the highest temperatures and pressures of the biosphere. Cultured
      bacterial isolates can grow to over 100 MPa at 2 degrees C and to over 40 MPa at
      over 100 degrees C. These cultures comprise the foundation for the study of the
      molecular biology and biotechnology of these isolates. The PTk diagram shows how
      temperature and pressure affect the growth rate of a bacterium and helps in the
      search for relationships among bacteria from habitats differing in temperature
      and pressure.

PMID- 8561480
TI  - Viral vectors in gene therapy.
AB  - The use of DNA as a drug is both appealing and simple in concept. Indeed in many
      instances the feasibility of such an approach has been established using model
      systems. In practical terms, however, the delivery of DNA to human tissues
      presents a wide variety of problems that differ with each potential therapeutic
      application. In this review, the design, production, and application of viral
      vectors for human gene therapy are considered. Although viral vectors are an
      obvious starting point because viruses have evolved efficient mechanisms to
      introduce and express their nucleic acid into recipient cells, by the same token
      the viral hosts have evolved sophisticated mechanisms to rid themselves of such
      pathogens. The challenge for the therapeutic use of viral vectors is to achieve
      efficient and often extended expression of the exogenous gene while evading the
      host defenses. Methodology used and progress towards that goal are reviewed.

PMID- 8561481
TI  - Physiological implications of sterol biosynthesis in yeast.
AB  - Fungi are among the most primitive organisms that synthesize sterols. The fungal
      sterol, ergosterol, is similar to animal sterol, cholesterol, but with
      significant structural differences. The genetics and biochemistry for most of the
      steps in sterol biosynthesis have been studied in the yeast, Saccharomyces
      cerevisiae. Yet, little is known of the precise physiological roles that sterols
      play in the cell. Work with strains that are auxotrophic for ergosterol has led
      to the prediction of at least four growth-dependent functions for sterols. Most
      of the antifungal compounds in medical and agricultural use affect some aspect of
      sterol synthesis or function. Extensive studies on the modes of action of those
      substances and research on the effects of altering sterol metabolism by sterol
      mutants are providing new insights into sterol functions in the cells. In
      addition, questioning why fungi require ergosterol rather than the simpler
      cholesterol provides heuristic impetus for further experimentation.

PMID- 8561482
TI  - Effects of a model on food neophobia in humans.
AB  - In study 1, subjects who were high and low in trait food neophobia made a series
      of choices between novel or familiar foods in the presence of no model, a
      neophilic model who chose mostly novel foods, or a neophobic model who chose
      mostly familiar foods and made another series of choices in private from foods
      which were not modeled. Subjects who were low (but not high) in trait neophobia
      behaved in accordance with the behavior of the neophilic (but not neophobic)
      model in the model's presence (but not absence). Study 2 clarified the results of
      study 1, revealing that the phenomenon was modeling and not conformity, that even
      highly neophobic subjects can be influenced by a stronger modeling manipulation,
      that food neophobia can be both increased and decreased, and that the reduced
      neophobia induced by exposure to a neophilic model does not generalize to non
      modeled foods.

PMID- 8561483
TI  - Restrained eating and dieting: replication of their divergent effects on eating
      regulation.
AB  - This study examined the replicability of findings reported by Lowe, Whitlow and
      Bellwoar (1991) concerning eating regulation among restrained eaters and dieters.
      Lowe et al. found that current dieters ate more than restrained non-dieters when
      not preloaded, and sharply reduced their intake following a high-calorie preload.
      The present study re-examined these findings and also determined the effect on
      intake of a high-calorie preload described as low in calories. The results
      replicated those reported by Lowe et al., with non-preloaded dieters showing
      increased eating and preloaded dieters showing reduced eating. In the "low
      calorie" condition, current dieters ate an intermediate amount. These findings
      bolster recent arguments (Lowe, 1993) that restraint and dieting are different
      phenomena which have divergent effects on eating behavior.

PMID- 8561484
TI  - Low-fat (41%) butter consumption decreases total energy and lipid intake in
      diabetic patients under acute conditions.
AB  - Decreasing fat intake in subjects at risk of cardiovascular diseases and
      particularly diabetics is a major issue. To investigate whether low-fat (41%)
      butter (LFB) is of any benefit compared to regular butter (RB), 97 hospitalized
      diabetics (41 insulin-dependent) were studied on four consecutive days. Breakfast
      (bread, butter and drink) was served at 0830 hrs, on successive mornings. LFB and
      RB were presented ad libitum, on alternate days. Satiety was assessed at 10 and
      12 h, using line rating scales. At 1230 hrs lunch was served, with large servings
      corresponding to 130% of the recommended lunch intake, so that carry-over effects
      from the breakfast manipulation could be measured. At breakfast, LFB was consumed
      in higher amounts, 27 vs. 21 g, F(1,96) = 33.24, p < 0.0001, than RB; however,
      the energy intake was significantly lower (by about -38%) on LFB days, F(1,96) =
      158.3, p = 0.0001. Hunger at 10 h but not at 12 h was affected by breakfast
      conditions. Lunch intake was comparable following LFB and RB breakfasts. In
      conclusion, LFB utilization under acute conditions seems to benefit diabetics by
      reducing caloric and fat intake.

PMID- 8561485
TI  - Low-fat (41%) butter use decreases butter lipid intake over 4-week trials in
      healthy persons.
AB  - All members of 18 families (n = 75; ages from 1 to 65 years) participated in a
      cross-over study of butter usage. Two types of butter were compared: regular
      (82%) fat) and low-fat (41%) butter. Butter was supplied to the families by the
      laboratory for use in raw (spread) form over two successive periods of 5 weeks
      (first week served as training). No other butter was allowed. The number of
      consumers (75) remained constant throughout the study. Over four consecutive
      weeks, the families consumed as much low-fat as regular butter (10.70 +/- 1 g
      versus 10.06 +/- 1.17 g per day per person). However, lipid intake from butter
      was significantly reduced during the low-fat butter period as compared to the
      regular butter period (4.39 +/- 0.41 g versus 8.25 +/- 0.96 g per day per person,
      p = 0.0005). Since previous studies showed that nutrient-specific compensatory
      intake is unlikely, it is suggested that use of low-fat butter can facilitate a
      reduction in fat intake over extended periods of time in healthy persons.

PMID- 8561486
TI  - Meal pattern during the transient hypophagia of rats switched from a high fat to
      a high carbohydrate diet.
AB  - Meal pattern was investigated during the transient hypophagia lasting about 1
      week when rats are switched from a carbohydrate-free high fat (HF) diet to an
      isocaloric high carbohydrate (HC) diet. After the HF/HC diet switch, voluntary
      food intake was suppressed through reduction of meal size with meal frequency
      remaining unaffected. Thus, the satiety ratio was increased in HF rats ingesting
      the HC diet. The observation that the first meal after the HF/HC switch, unlike
      the following meals, was not yet diminished, suggests that conditioning is
      involved in the reduction of meal size resulting from the switch. About 1 week
      after the dietary switch, the feeding pattern of rats had adjusted to that of
      rats receiving the HF diet. Unlike the HF/HC switch, the HC/HF switch did not
      reduce cumulative food intake, but decreased meal size and increased meal
      frequency during the first day. It is suggested that the transient decrease in
      meal size and increase in satiety ratio following the HF/HC diet switch arises
      partly from a relatively high postabsorptive satiating potency of glucose related
      to a low rate of glucose disposal found in previous work under such conditions. A
      transiently reduced gastrointestinal clearance of carbohydrate may also be
      involved.

PMID- 8561487
TI  - Dehydroepiandrosterone and macronutrient selection by obese Zucker rats (fa/fa).
AB  - The effect of dehydroepiandrosterone (DHEA) on the macronutrient preference and
      total energy intake of lean and obese female Zucker rats was studied.
      Introduction of DHEA led to a rapid decrease in the consumption of fat, protein
      and total calories by the obese rat. DHEA treatment of the lean rat caused a
      change neither in its total energy consumption nor in its fat consumption, but
      did cause a distinct expression of preference for carbohydrate over protein. Both
      lean and obese animals gained weight rapidly during the steroid-free weeks and
      lost weight while consuming the DHEA-supplemented diet. The difference in weight
      changes seen with the obese rats between the DHEA-free and DHEA-supplemented
      periods could be accounted for by differences in caloric intake. Lean rats,
      however, did not change their total energy intake during DHEA-treatment periods;
      therefore, DHEA caused weight loss in the lean rat probably by altering energy
      metabolism. It is concluded that in the obese, young, female Zucker rat, DHEA
      alters macronutrient preference as well as caloric intake. In the lean rat, DHEA
      has a more subtle effect on relative macronutrient preference and not on total
      energy consumption.

PMID- 8561488
TI  - Cognitive factors in the dietary response of restrained and unrestrained eaters
      to manipulation of the fat content of a dish.
AB  - This study examined the dietary intake and rated internal state of 16 normal
      weight young women following the manipulation of the actual or the presented fat
      and energy content of a test dish eaten at lunch. Half of the subjects were
      classified as restrained and half as unrestrained eaters. The test dish was
      either 2473 kJ (591 kcal) in its high-fat version or 1485 kJ (355 kcal) in its
      low-fat version, and was provided either with a correct or incorrect information
      about its fat content. All the intakes at the three meals during the following 8
      h were covertly recorded in the laboratory, and internal state rated on four
      occasions. After the low-fat test dish presented as low-fat, unrestrained eaters
      increased their energy intake compared to that in other conditions. Restrained
      subjects did not exhibit this pattern and compensated for the missing energy in
      the low-fat test dish, compared to the high-fat test dish, only when they were
      informed that both dishes were high in fat. Irrespective of the information, both
      restrained and unrestrained subjects reported weaker sensations of hunger after
      the actual high-fat test dish than after the actual low-fat test dish whereas
      only restrained eaters reported stronger sensations of fullness. Thus, the
      influence of the cognitive factors on food intake and ratings of internal state
      is modulated by restrained eating behaviour.

PMID- 8561489
TI  - Binge eating following biliopancreatic diversion for obesity.
AB  - The prevalence of binge eating disorder (BED) was assessed in 68 massively obese
      patients prior to and following biliopancreatic diversion (BPD) for obesity. The
      eating behavior and the psychological traits were evaluated by the Three Factor
      Eating Questionnaire and the Eating Disorder Inventory. Since after BPD the body
      weight regulation is substantially dependent on intestinal absorption, the
      individuals operated on have to be considered as absolutely free eaters. In this
      population, 30 patients were affected by BED and in 24 of them binge eating
      disappeared spontaneously following BPD, highlighting the main role of
      preoccupation with food, diet and overweight in causing or in maintaining BED.

PMID- 8561490
TI  - Consistency of liking and appropriateness ratings and their relation to
      consumption in a product test of ice cream.
AB  - The consistency of hedonic responses to three brands of vanilla ice cream over 5
      weeks was examined using two procedures. Respondents (n = 40) came to the test
      after their usual lunch and rated their liking for ice creams side-by-side (three
      samples in one session) and after ad libitum consumption (one sample at a time).
      The quantity of ice cream consumed in ad libitum procedure was recorded.
      Respondents also assessed the appropriateness of the three samples of vanilla ice
      cream to ten usage situations, including "as a dessert" which was the context in
      the test situation. The consistency of hedonic responses was low over replicates
      (r = 0.03 to 0.48). In the side-by-side condition, only 48% of the liking
      responses in replicates were within one point (not at all = 1, extremely = 9),
      and 63% in the after-consumption condition. Some respondents ate more of all
      brands than other subjects did in both replicates, unrelated to differences in
      liking. The appropriateness ratings of brands were similar but the ratings of
      appropriateness "as a dessert" differentiated the brands. In the after
      consumption condition the ratings of liking and appropriateness, together with
      consumption measures, appeared to be slightly more consistent at the individual
      level than those made in the side-by-side situation.

PMID- 8561491
TI  - Effect of beta-carotene and canthaxanthin on tert-butyl hydroperoxide-induced
      lipid peroxidation in murine normal and tumor thymocytes.
AB  - It has been reported that the anticarcinogenic effect of carotenoids could be
      related to an antioxidant mechanism. The antioxidant efficiency of beta-carotene
      and canthaxanthin was evaluated in murine normal and tumor thymocytes. Normal and
      tumor cells were exposed under air to tert-butyl hydroperoxide (t-BOOH) and lipid
      peroxidation was measured in the absence or in the presence of the two
      carotenoids. Our results show that: (a) Both carotenoids, added at effective and
      comparable concentrations (from 1 to 50 microM), were able to inhibit t-BOOH
      induced malondialdehyde formation in a dose-dependent manner. (b) Canthaxanthin
      was a more potent antioxidant that beta-carotene. (c) The inhibition of lipid
      peroxidation was greater in tumor thymocytes. (d) Carotenoids were consumed
      differentially during the incubation with the prooxidant. beta-Carotene was
      consumed faster than canthaxanthin and in a larger amount in tumor than in normal
      thymocytes. The addition of the iron chelator deferoxamine or the SH group
      reducing agent dithiothreitol reduced t-BOOH-induced beta-carotene consumption in
      tumor cells but not in normal ones. (e) The loss of endogeneous alpha-tocopherol
      induced by t-BOOH was enhanced by the addition of beta-carotene, suggesting the
      possibility of oxidative interactions between the two antioxidants. These results
      confirmed the antioxidant effectiveness of carotenoids in normal and tumor cells,
      although differences depending on the kind of cells and carotenoids used were
      found.

PMID- 8561492
TI  - Pyrraline ether crosslinks as a basis for protein crosslinking by the advanced
      Maillard reaction in aging and diabetes.
AB  - Pyrraline (epsilon 2-(formyl-5-hydroxymethyl-pyrrol-1-yl)-L- norleucine) is an
      advanced Maillard reaction product derived from the reaction of glucose with
      lysine amino group on proteins. Its presence in plasma and tissue proteins has
      been established by immunological and chromatographic methods. The purified
      preparation of pyrraline obtained from the reaction of glucose with lysine when
      stored at room temperature or at refrigeration turned pink in color, suggesting
      spontaneous formation of degradation products. These products were analyzed by
      high-performance liquid chromatography and one of the products was isolated to
      purity. The structure of the compound was established to be a dipyrraline formed
      by an ether bond between two pyrraline molecules. This finding led us to
      investigate the reactivity of pyrraline with thiol and hydroxy amino acids. The
      hydroxy amino acids were in general nonreactive, except hydroxy lysine and
      hydroxy proline which formed minor condensation products. While the reaction of
      cysteine resulted in the formation of two distinct thioethers, the reaction of
      glutathione resulted in the formation of two major unidentified compounds which
      gradually degraded upon incubation. These data suggest that pyrraline formed in
      vivo can further react with other amino acids on proteins to form crosslinks,
      which may explain in part increased protein crosslinking associated with aging
      and diabetes.

PMID- 8561493
TI  - Purification of a phenobarbital-inducible UDP-glucuronosyltransferase isoform
      from dog liver which catalyzes morphine and testosterone glucuronidation.
AB  - A morphine UDP-glucuronosyltransferase (UGT) which could belong to the UGT2B
      subfamily was isolated from liver microsomes of a male beagle dog treated with
      phenobarbital. Glucuronidation toward morphine in the dog liver microsomes was
      increased threefold by the treatment. The microsomes were solubilized with
      Emulgen 911 and applied on a column of hemisuccinate derivative of Sepharose 4B
      column which has been developed in our laboratory. An isoform of UGT in the
      eluate was purified further by chromatofocusing and UDP-hexanolamine-affinity
      chromatography. A purified enzyme, UGTDOG-PB, was homogeneous on sodium dodecyl
      sulfate polyacrylamide gel electrophoresis and two-dimensional electrophoresis
      and exhibited a subunit molecular weight of 50 kDa. This isoform showed
      activities toward the 3-hydroxyl group of morphine, 4-hydroxybiphenyl, 4
      nitrophenol, 4-methylumbelliferone, and testosterone, but not toward
      chloramphenicol and the 6-hydroxyl group of morphine. The substrate specificity
      of UGTDOG-PB is similar to that of stably expressed UGT2B1 which is considered a
      phenobarbital-inducible morphine UGT in the rat except that UGTDOG-PB is capable
      of glucuronidating 4-nitrophenol but not chloramphenicol. The NH2-terminus until
      the 30th residue of UGTDOG-PB is highly homologous to UGT2B subfamily, and the
      NH2-terminal 15 residues of UGTDOG-PB are completely identical to those of
      UGT2B1, UGT2B8, and UGT2B15. This is the first report describing the UGT isoform
      of dog and the purification of morphine UGT which may belong to UGT2B subfamily.

PMID- 8561494
TI  - An amino acid derived from aldol crosslink of elastin and collagen: structure,
      distribution, aging, and two models of hyperglycemia.
AB  - A novel amino acid named aldosine was isolated from acid hydrolysates of bovine
      aorta elastin. The mass spectral analysis of aldosine indicated a parent compound
      with a mass of 256 (C12H20N2O4). From the structure identified by spectroscopy of
      aldosine and its derivatives, it was deduced that aldosine was derived from aldol
      crosslink and dehydromerodesmosine of elastin and collagen. The aldosine content
      in aorta of newborn rats was very low, but increased markedly with growth. After
      maturity was reached, the aldosine content decreased. The aldosine content in
      bovine aorta decreased gradually from 7 months to 16 years of age. Aldosine was
      also quantified in the aorta and tail tendon of rats in two models of
      hyperglycemia: diabetes and galactosemia. Hyperglycemias were significantly
      affected on aldosine content of organs. In both diabetic and galactosemic
      animals, aldosine was remarkably lower relative to controls (about one-half and
      one-sixth, respectively).

PMID- 8561495
TI  - Roles of cytochrome b5 in the oxidation of testosterone and nifedipine by
      recombinant cytochrome P450 3A4 and by human liver microsomes.
AB  - NADH-dependent testosterone 6 beta-hydroxylation and nifedipine oxidation
      activities could be reconstituted in systems containing cytochrome b5 (b5), NADH
      b5 reductase, and bacterial recombinant cytochrome P450 (P450) 3A4 with a
      synthetic phospholipid mixture, cholate, MgCl2, and reduced glutathione.
      Replacement of NADH-b5 reductase with NADPH-P450 reductase produced an eightfold
      increase in testosterone 6 beta-hydroxylation activity. Further stimulation could
      be obtained when NADPH was used as an electron donor instead of NADH. Removal of
      b5 from the NADH- and NADPH-supported systems caused a 90% loss of testosterone 6
      beta-hydroxylation activities in the presence of NADPH-P450 reductase but
      resulted in complete loss of the activities in the absence of NADPH-P450
      reductase. These results suggested that about 10% of the activities was due to
      electron flow from NADPH-P450 reductase to P450 3A4 in the absence of b5. In the
      presence of testosterone and MgCl2, P450 3A4 was reduced by b5 and NADH-b5
      reductase, although the rate of P450 3A4 reduction was much slower than that by
      NADPH-P450 reductase. Anti-human b5 immunoglobulin G (IgG) (purified using rabbit
      b5 affinity chromatography) inhibited testosterone 6 beta-hydroxylation activity
      catalyzed by human liver microsomes more strongly in NADH- than in NADPH
      supported reactions. However, anti-rat NADPH-P450 reductase IgG inhibited
      microsomal activities in both NADH- and NADPH-supported systems to similar
      extents. Addition of NADH enhanced NADPH-supported testosterone and nifedipine
      oxidations in human liver microsomes. MgCl2 stimulated rates of reduction of b5
      by NADPH-P450 reductase, but not by NADH-b5 reductase, in reconstituted systems.
      These results suggest that b5 is an essential component in P450 3A4-catalyzed
      testosterone hydroxylation and nifedipine oxidation in human liver microsomes.
      Our previous observation that rates of reduction of ferric P450 3A4 by NADPH-P450
      reductase are accelerated by complexation with substrates and b5 is supported in
      this study.

PMID- 8561496
TI  - Viscoelastic properties of F-actin solutions in the presence of normal and
      mutated actin-binding proteins.
AB  - A minimal level of viscoelasticity in the cytoskeleton is an essential
      prerequisite of cellular motility. To determine the influence of the F-actin
      crosslinking proteins alpha-actinin and actin-binding protein (ABP)120 gelation
      factor from Dictyostelium discoideum on the properties of actin gels we used a
      torsion pendulum to measure directly viscoelastic changes of the filamentous
      networks. Using the capping proteins severin and DS151 to control actin filament
      length, both crosslinkers were found to increase the elasticity and the viscosity
      of F-actin solutions. In the case of alpha-actinin, this activity was completely
      blocked by micromolar concentrations of Ca2+. The inhibitory functions of the two
      EF hands of alpha-actinin were further investigated by introducing point
      mutations into either one or both of the Ca(2+)-binding regions. Mutations in the
      Ca(2+)-coordinating amino acid residues in the first or in both EF hands left the
      dynamic storage and loss moduli of the F-actin solution unaltered, independent of
      the Ca2+ concentration. However, alpha-actinin mutated in the second EF hand
      increased the viscoelasticity of actin gels like the wild-type protein in the
      absence of Fa2+. The ABP120 gelation factor exhibited only negligible differences
      to alpha-actinin in viscometry measurements, whereas its impact on the ratio
      G"/G' (the ratio of energy lost compared to elastically stored during a
      deformation) of F-actin solutions was clearly smaller than that of alpha-actinin.
      We conclude from these data that: (i) a torsion pendulum is an excellent tool to
      determine small changes of activity in normal and mutated actin-binding proteins,
      (ii) the first EF hand of alpha-actinin is crucial for its crosslinking function,
      and (iii) the viscoelastic properties of F-actin gels crosslinked by either alpha
      actinin or the ABP120 gelation factor are different.

PMID- 8561497
TI  - Proteoglycans and proteins in the extracellular matrix of mouse cumulus cell
      oocyte complexes.
AB  - In the preovulatory follicle, the oocyte is surrounded by approximately 1000
      closely associated cumulus cells forming the compact form of the cumulus cell
      oocyte complex (COC). In response to the gonadotropin surge, the COC in a
      follicle destined for ovulation undergoes expansion when the cumulus cells
      synthesize and organize an extensive extracellular matrix enriched in hyaluronan.
      Successful expansion of the COC appears to be essential for ovulation and
      ultimately for fertilization. We studied this process in vitro by isolating
      compact COCs from preovulatory mouse follicles and incubating them under
      conditions which promote COC expansion by retention of newly synthesized
      hyaluronan (HA in the extracellular matrix around the cells. [3H]-Leucine and
      [35S]sulfate were used as precursors to label macromolecules synthesized by the
      cells that may be necessary for organizing the HA in this matrix. After labeling,
      expanded COCs were washed to remove medium and any labeled molecules that were
      not associated with the matrix. Macromolecules selectively associated with the
      matrix were then solubilized by digesting the expanded COCs briefly with
      Streptomyces hyaluronidase, an enzyme that specifically cleaves HA. Cells were
      removed by centrifugation, and the digest supernate was analyzed by molecular
      sieve chromatography and SDS-PAGE. A dermatan sulfate proteoglycan of large
      hydrodynamic size ( > 1 million Da) and a approximately 46-kDa protein were the
      predominant labeled species identified. The proteoglycan has properties similar
      to proteoglycans such as aggrecan and versican which interact specifically with
      HA. The approximately 46-kDa protein has the same molecular size as the link
      protein which interacts with HA and HA-binding proteoglycans to form stable
      ternary complexes in a variety of extracellular matrices. We propose that the
      dermatan sulfate proteoglycan and the approximately 46-kDa protein synthesized by
      the cumulus cells form similar ternary complexes that are necessary for retaining
      HA in the COC matrix and hence are required for successful COC expansion.

PMID- 8561498
TI  - Structural studies of a major hemorrhagin (rhodostoxin) from the venom of
      Calloselasma rhodostoma (Malayan pit viper).
AB  - The complete amino acid sequence, disulfide linkages, glycosylation sites, and
      carbohydrate structure of rhodostoxin, the major hemorrhagin from Calloselasma
      rhodostoma (Malayan pit viper), have been determined. This sequence confirmed the
      deduced amino acid sequence of the putative hemorrhagic protein encoded by the
      prorhodostomin cDNA of C. Rhodostoma. Rhodostoxin contained four disulfide bonds
      that link Cys19-Cys60, Cys117-Cys198, Cys157-Cys182, and Cys159-Cys165. It is the
      first four-disulfide proteinase reported among all known venom
      metalloproteinases, which are either of the two-disulfide or three-disulfide
      type. Peptide-mapping and dot-blotting experiments showed the presence of two
      glycopeptides. Subsequent sequencing of these peptides established that the N
      glycosylation sites are located at residues 91 and 181 of the amino acid sequence
      of the matured protein. Mass spectrometric analyses of these glycopeptides showed
      that they contain an oligosaccharide structure consisting of 4 units of N
      acetylglucosamine, 5 units of hexose, 1 unit of fucose, and 2 units of neuraminic
      acids. The complete carbohydrate structure was then established by 2-D mapping
      analysis of the pyridylamino-oligosaccharides after hydrazinolysis and
      pyridylamination of the glycan chains.

PMID- 8561499
TI  - Ribonuclease H activity during initiation of reverse transcription using
      tRNA(lys)/RNA primer/template of human immunodeficiency virus.
AB  - The specificity of the initial cleavage by the RNaseH activity of HIV-1 reverse
      transcriptase (RT) during minus strong-stop DNA synthesis was studied using the
      authentic primer/template tRNA(lys)/HIV RNA. We observed that concomitant with
      the initiation of DNA synthesis, RNaseH activity of HIV RT introduced the first
      endonucleolytic cuts within the U5 region of the HIV RNA template, mainly 1 and 3
      bases away from the primer binding site. To analyze whether the cleavage sites
      were determined by sequence specificity, the authentic U5 region at one of the
      cleavage sites was mutated. The change of sequence did not alter the initial
      cleavage pattern of RNaseH. In order to determine the size of the RNA/DNA hybrid
      that is required for RNaseH activation during reverse transcription initiation,
      DNA synthesis was limited by dideoxynucleotides. DNA extension of the tRNA(lys)
      primer by 17 deoxyribonucleotides but not by 6 deoxyribonucleotides was
      sufficient to activate the RNaseH site of HIV RT. Taken together, our results
      indicate that during initiation of minus strongstop DNA synthesis by HIV RT, the
      first RNaseH-mediated endonucleolytic cut of the genomic RNA is dictated mainly
      by the length of the nascent DNA and not by sequence preference.

PMID- 8561500
TI  - Purification, cDNA cloning, and expression of human sorcin in vincristine
      resistant HOB1 lymphoma cell lines.
AB  - Human sorcin, M(r) 22-kDa/pI 5.3, was identified in HOB1 lymphoma cells resistant
      to 1.0 microM vincristine and polyclonal antibody against it was produced. Using
      antibody to precipitate sorcin from 32P-labeled cell extract, the SDS-PAGE
      resolved human sorcin was not phosphorylated in contrast to the report of A. M.
      van der Bliek et al. ((1986) EMBO J. 5, 3201-3208) in which the authors
      emphasized hamster sorcin might be phosphorylated through a cAMP-dependent
      protein kinase. Although sorcin had not been found among proteins of parental
      HOB1 cells labeled by [35S]-methionine and resolved by 2-D -PAGE, it could be
      immunoprecipitated from the cytosolic extract of the same cells. In vitro
      phosphorylation study did not reveal an enhanced phosphoprotein located in the
      area of 22 kDa, either. A 521-bp human sorcin cDNA fragment synthesized by PCR
      was used to screen cDNA library constructed from mRNA of HOB1/VCR1.0 cells. Human
      sorcin cDNA encoded 198 amino acids, 10 among which have been replaced in hamster
      sorcin. Of the 10 amino acid changes, 6 involve serine's in human sorcin compared
      to hamster's 1. These data suggest a difference in phosphorylation state between
      the two species. The results of Southern blot indicate the sorcin gene was
      amplified in HOB1/VCR1.0 cells under the pressure of high concentration of
      vincristine but not secondary to the mdr gene amplification. 2-step PCR,
      exhibiting the gene could be latently expressed in parental HOB1 cells, confirms
      the above result of immunoprecipitation. Interestingly, HOB1/VCR0.5 cells
      (resistant to 0.5 microM vincristine) do not show amplification of the gene but
      do have increased expression of the protein. When this cell line was cultured in
      0.1 microM vincristine for a period of time, the protein's expression amount
      reverted to the latent level. These results suggest that sorcin should have a
      place in mediating resistance of HOB1 cells to vincristine.

PMID- 8561501
TI  - Inactivation of nitric oxide synthase isoforms by diaminoguanidine and NG-amino-L
      arginine.
AB  - Diaminoguanidine (DAG) and NG-amino-L-arginine each produced a time- and
      concentration-dependent inactivation of the citrulline-forming activity of all
      three NOS isoforms. DAG inactivates both the NADPH-oxidase and the citrulline
      forming activities of GH3 pituitary nNOS while NG-amino-L-arginine inactivates
      only its citrulline-forming activity. The inactivation by DAG of GH3 nNOS NADPH
      oxidase and citrulline forming activities is stimulated by (6R)-5,6,7,8
      tetrahydrobiopterin (BH4) cofactor, follows pseudo-first-order kinetics and is
      not substrate saturable. DAG-induced inactivation of the citrulline-forming
      activity for the iNOS and eNOS isoforms displayed maximal inactivation rates of
      0.37 and 0.14 min-1 and Ki values of 385 and 670 microM, respectively. At 1 mM
      DAG and saturating BH4, half-times of inactivation of 0.7, 8, and 2 min were
      observed for the nNOS, eNOS, and iNOS isoforms, respectively. NG-Amino-L-arginine
      induced inactivation of the citrulline-forming activity of the nNOS, iNOS, and
      eNOS isoforms displayed maximal inactivation rates of 0.35, 0.26, and 0.53 min-1
      and Ki values of 0.3, 3, and 2.5 microM, respectively. The inactivation of the
      NOS activities by both DAG and NG-amino-L-arginine in preincubations required the
      presence of oxygen and Ca2+, consistent with an inactivation mechanism that
      requires active metabolism by NOS. Methylguanidine and 1,1-dimethylguanidine
      exhibited a reversible inhibition pattern in contrast to all three NOS isoforms.
      Neither agent exhibited significant isoform selectivity.

PMID- 8561502
TI  - Structure-function relationships of phenylalanine hydroxylase revealed by
      radiation target analysis.
AB  - Phenylalanine hydroxylase (PAH) purified from rat liver is an oligomeric protein
      (predominantly tetramers) composed of 52-kDa subunits that are identical in
      primary structure. We have used radiation target analysis to probe the subunit
      organization of the enzyme. When 6-methyltetrahydropterin was used as the
      cofactor, the loss of hydroxylase activity as a function of radiation dose was
      defined by a single exponential decay, yielding a target size of about 120 kDa.
      However, when the enzyme was assayed with the natural cofactor
      tetrahydrobiopterin (BH4), the inactivation curves were much more complex. In
      these cases, the activity first increased, then decreased, as a function of
      radiation dose. The inactivation profile at higher radiation doses implied a
      target size of approximately 100 kDa. Kinetic analysis of the enzyme was
      significantly activated relative to the nonirradiated sample. In addition, the
      irradiated enzyme was desensitized to substrate-level activation by
      phenylalanine. The initial increase in activity at low radiation doses is due to
      the destruction of a large inhibitor. Analysis of the irradiated samples by high
      performance size-exclusion chromatography indicated that the hydroxylase tetramer
      was lost with a target size of 110 kDa. Our data indicate that the tetrameric
      form of purified PAH consists of two enzymatically active dimers and that BH4
      interacts with a tetramer to inhibit or deactivate the enzymatic activity.

PMID- 8561503
TI  - Inhibitors of cholesterol biosynthesis increase hepatic low-density lipoprotein
      receptor protein degradation.
AB  - Inhibitors of cholesterol biosynthesis are believed to lower serum cholesterol
      levels by enhancing the removal of serum low-density lipoprotein (LDL) by
      increasing hepatic LDL receptor function. Thus, the effects of several different
      inhibitors of cholesterol biosynthesis were examined for their effects on the
      expression of the hepatic LDL receptor in rats. We found that administration of
      inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase such as lovastatin,
      pravastatin, fluvastatin, and rivastatin resulted in increased hepatic LDL
      receptor mRNA levels. Surprisingly, these agents failed to increase levels of
      immunoreactive LDL receptor protein in rat liver even when the dose and length of
      treatment were increased. Treatment of rats with zaragozic acid A, an inhibitor
      of squalene synthase, caused even greater increases in hepatic LDL receptor mRNA
      levels, but did not increase levels of immunoreactive protein. Further
      investigation revealed that the rate of degradation of the hepatic LDL receptor
      was increased in rats given inhibitors of cholesterol biosynthesis. The greatest
      increase in the rate of degradation was seen in animals treated with zaragozic
      acid A which caused the largest increase in hepatic LDL receptor mRNA levels. In
      contrast, hepatic LDL receptor protein was stabilized in cholesterol-fed rats. It
      appears that increased potential for LDL receptor protein synthesis, reflected in
      increased mRNA levels, is offset by a corresponding increase in the rate of
      receptor protein degradation resulting in constant steady-state levels of hepatic
      LDL receptor protein. These findings are suggestive of increased cycling of the
      hepatic LDL receptor. This postulated mechanism can provide for enhanced hepatic
      uptake of lipoproteins without increasing steady-state levels of LDL receptor
      protein.

PMID- 8561504
TI  - Acetyl coenzyme A carboxylase activity in neonatal rat cardiac myocytes in
      culture: citrate dependence and effects of hypoxia.
AB  - The presence of a 280,000 M(r) isoform of acetyl-CoA carboxylase (ACC-280) in the
      cardiac myocyte suggests that heart muscle is capable of malonyl-CoA synthesis.
      Cellular factors which regulate activity of ACC-280 are unknown. We have employed
      a neonatal rat cardiac myocyte culture (where the majority of ACC is present as
      ACC-280) to examine the effects of hypoxia and decreased cellular ATP on the
      activity of ACC in the cells. The myocyte culture has the following advantages
      over similar studies in the intact rat heart: the presence of a pure population
      of myocytes and the ability to measure cytosolic ACC free from contamination by
      mitochondrial carboxylases. ACC activity in cultured cardiac myocytes is
      completely dependent on the presence of citrate (A0.5=3.8 mM). Under control
      conditions, the cytosolic citrate concentration in situ is determined to be less
      than 1 mM. With 5 h of hypoxia, cytosolic ATP decreases from 9.85 +/- 0.23 to
      2.83 +/- 0.25 mM and cytosolic AMP increases from undetectable levels to 40 +/-
      0.4 microM. With hypoxia, a significant portion of the total ACC activity is now
      expressed in the absence of citrate and the amount of activity which is
      stimulated by 10 mM citrate is significantly less (1,268 +/- 0.106 nmol/4 x 10(5)
      cells) than is seen under control conditions (3.042 +/- 0.048). There are no
      significant changes in the total amount of cellular protein on the plates after 5
      h of hypoxia. Consistent with net ACC activation in hypoxia, malonyl-CoA levels
      increase in the cells by 7 h of hypoxia. Decreased radioactive phosphate content
      of immunopurified ACC-280 after 5 h of hypoxia is consistent with net
      dephosphorylation of ACC-280 and increased citrate-independent activity.

PMID- 8561505
TI  - Hydrogen peroxide induces the expression of adapt15, a novel RNA associated with
      polysomes in hamster HA-1 cells.
AB  - In mammalian cells, hydrogen peroxide is known to induce the expression of
      several genes thought to be important in protection against oxidative stress.
      Using mRNA differential display, we have identified a novel RNA in hamster HA1
      cells that is strongly induced by hydrogen peroxide under conditions where a
      protective adaptive response occurs. This induction was observed between 1 and 18
      h after peroxide treatment, and at an H202 concentration that caused little or no
      cytotoxicity. Northern blot analysis revealed that this major inducible RNA
      species, termed adapt15, is 950 bases in size. Two versions of this RNA were
      found by sequence analysis, differing only by a short trinucleotide stretch.
      Despite polyadenylation, no large open reading frame was observed. Fractionation
      studies, however, indicate that adapt15 RNA is primarily located in the
      cytoplasm, and a significant percentage of it is associated with active
      translation. adapt15 RNA may act at the level of translation to protect cells
      against the damaging effect of oxidative stress.

PMID- 8561506
TI  - Substrate influence on interaction between cytochrome P450 and cytochrome b5 in
      microsomes.
AB  - We have been able to demonstrate that cytochrome b4 interacts closely with
      cytochrome P450 in the microsomal membrane, and that substrates can serve to
      order the interaction: Using the water-soluble carbodiimide EDC we could
      crosslink cytochrome b5 and CYP2B4 in microsomes from phenobarbital-treated
      rabbits and cytochrome b5 and CYP1A2 in microsomes from beta-naphthoflavone
      treated animals. The substrate benzphetamine increased the specific interaction
      between cytochrome b5 and CYP2B4, decreasing the formation of higher molecular
      weight oligomeric complexes with cytochrome b5. In contrast, no ordering of the
      interactions were obtained on addition of 7-ethoxycoumarin, a substrate of
      CYP1A2, or of benzphetamine to microsomes of beta-naphthoflavone-treated animals
      in the presence of EDC. Of interest, although evidence could be shown for
      complementary charge-pairing between cytochrome b5 and a number of other
      microsomal proteins in the membranes, and while the extent of CYP1A2 and CYP2B4
      interaction with cytochrome b5 each exceeded 30% in the presence of substrate, no
      significant complexation of the P450s was obtained with any other microsomal
      proteins.

PMID- 8561507
TI  - The sequencing expression, purification, and steady-state kinetic analysis of
      quinolinate phosphoribosyl transferase from Escherichia coli.
AB  - The nadC gene from Escherichia coli was isolated and sequenced. The gene was then
      cloned into an expression vector and, following transformation, the resulting
      bacteria were able to produce quinolinate phosphoribosyl transferase as about 2%
      of the soluble protein. The enzyme was purified in five steps leading to a
      homogeneous preparation. The enzyme reaction shows an ordered binding mechanism
      where the magnesium ion complex of 5-phosphoribosyl-1-pyrophosphate binds first
      followed by quinolinic acid. The products are pyrophosphate CO2, and nicotinate
      mononucleotide. Product inhibition studies show that nicotinate mononucleotide is
      a competitive inhibitor with respect to 5-phosphoribosyl-1-pyrophosphate while
      pyrophosphate is noncompetitive with respect to both 5-phosphoribosyl-1
      pyrophosphate and quinolinic acid. Phthalic acid and fructose-1,6-bisphosphate
      were used as dead-end inhibitors. Phthalate was competitive with respect to
      quinolinic acid but uncompetitive with respect to 5-phosphoribosyl-1
      pyrophosphate. Fructose-1,6-bisphosphate was a competitive inhibitor with respect
      to 5-phosphoribosyl-1-pyrophosphate and noncompetitive with respect to quinolinic
      acid. The Km values for the substrates are 15.6 microM for 5-phosphoribosyl-1
      pyrophosphate and 6.4 microM for quinolinic acid.

PMID- 8561508
TI  - Plant sterol biosynthesis: identification and characterization of higher plant
      delta 7-sterol C5(6)-desaturase.
AB  - Microsomes obtained from maize seedlings catalyzed the introduction of the delta5
      bond into delta7-sterols to yield the corresponding delta 5,7-sterols. Enzymatic
      bioassay conditions have been developed for the first time for delta 7-sterol
      C5(6)-desaturase in photosynthetic organisms. The properties of the microsomal
      system have been studied and the kinetics of the desaturation reaction has been
      established. The desaturation reaction requires molecular oxygen and NADH.
      Coenzyme efficiency studies indicate that NADH is more efficient that NADPH and
      that in the presence of NADH, NAD+ stimulates the desaturation process but cannot
      sustain the reaction by itself. The desaturation is strongly inhibited by
      cyanide, is sensitive to 1,10-phenanthroline and to salicylhydroxamic acid, but
      is insensitive to carbon monoxide, suggesting the involvement of a metal ion,
      presumably iron, in an enzyme-bound form in the desaturating system. From a
      series of incubations with delta 7-sterols and other sterol analogs, the
      substrate specificity for desaturation was determined. Our data indicate the
      substrate selectivity of the C5(6)-desaturation for 4-desmethyl-delta 7-sterols.
      Moreover, the results show that specificity of maize C5(6)-desaturase favored
      delta 7-sterols possessing a C24-methylene or ethylidene substituent compared to
      24-ethyl-substituted delta 7-sterols. Finally, the results demonstrate directly
      that during plant sterol synthesis the delta 5-bond is introduced via the
      sequence delta 7-sterol-->delta 5,7-sterol-->delta 5-sterol.

PMID- 8561509
TI  - Protein kinase CK2: biphasic kinetics with peptide substrates.
AB  - The regulatory beta-subunit of the protein kinase CK2 modulates the salt optimum
      for alpha-subunit activity. In the presence of salt the beta-subunit is
      stimulatory while in the absence of salt it is inhibitory. In the presence of 150
      mM NaCl CK2 has linear kinetics (Lineweaver-Burk) for the synthetic substrate
      RRRDDDSDDD with an apparent Km of 60 microM. In contrast, CK2 displayed biphasic
      kinetics for the peptide substrate when assayed in the absence of added NaCl.
      Biphasic kinetics were also obtained for other peptides but not for calsequestrin
      or casein. Recombinant alpha-subunit had strictly linear kinetics in the absence
      of added NaCl with an apparent Km of 104 microM. Preincubation of CK2 with
      ATP/Mg2+ or GTP/Mg2+, but not adenosine/Mg2+ or Mg2+ alone, resulted in kinetics
      that were near linear. This change in kinetics was dependent on enzyme conditions
      of low salt CK2 displays biphasic kinetics for peptide substrates, the biphasic
      kinetics require the presence of the beta-subunit, and ATP/Mg2+ binding reverses
      the effect.

PMID- 8561510
TI  - Gene expression of iron-related proteins during iron deficiency caused by scurvy
      in guinea pigs.
AB  - The regulation of expression of hepatic iron-related proteins was examined during
      iron deficiency caused by scurvy in guinea pigs. Previous studies showed that
      some effects of scurvy, such as suppression of collagen gene expression, result
      from events associated with weight loss. During the initial phase of scurvy when
      vitamin C is depleted but animals grow normally, serum iron levels decreased to
      50% of normal. During the second phase of scurvy when animals lose weight, there
      was a further decrease in iron levels to 10-15% of normal. Serum transferrin
      levels increased during scurvy, but this increase was related neither to the rate
      of weight loss nor to hepatic transferrin mRNA expression, which decreased. Serum
      ferritin levels of diminished early in scurvy with a preferential loss of the L
      subunit. In liver, however, both ferritin animals gaining weight. Ferritin gene
      expression during vitamin C deficiency was correlated with serum ferritin levels
      in that the level of mRNA for the H subunit remained relatively constant while
      that of the L subunit decreased early. Transferrin receptor mRNA expression in
      liver was induced as soon as iron levels decreased early in scurvy, which is
      similar to results reported for iron-depleted cultured cells. In contrast to
      results in cell culture, expression of iron regulatory protein 1 mRNA was
      decreased to approximately 50% of normal early in scurvy with a concomitant
      decrease in hepatic cytosolic aconitase activity. Our data indicate that iron
      deficiency occurs early during vitamin C deficiency and leads to changes in
      expression of iron-related proteins that differ in some aspects from regulation
      by iron in cell culture. Other events associated with weight loss in late scurvy
      may play a further role in this regulation.

PMID- 8561511
TI  - Managing costs and managing care: managing to make our systems humane.

PMID- 8561512
TI  - Psychiatric nursing outcome research: the state of the science.
AB  - A review of the nursing literature from 1989 to 1994 indicates that few
      psychiatric nursing studies are published in the major nursing research journals.
      The psychiatric specialization literature includes a large number of studies that
      are classified as either outcome studies or could serve as building blocks for
      future outcome studies. Few studies build on prior research, resulting in a weak
      scientific basis for evaluating the outcomes of psychiatric nursing care.
      Strategies for increasing the quantity and quality of psychiatric nursing outcome
      research are presented.

PMID- 8561513
TI  - Quality, cost-effective psychiatric treatment: A CNS--MD collaborative practice
      model.
AB  - Health care reform presents an opportunity to design alternative health care
      delivery models. Psychiatric clinical nurse specialists and psychiatrists are
      particularly well positioned to work together as full and equal partners, to
      complement each other's practice and to provide cost-effective care with improved
      patient outcomes. In this case study, we show that, with the addition of
      psychotherapy provided by a CNS, the cost of care for the patient decreased from
      over $40,000 (average hospital cost only) to less than $4,000 per year. In
      addition, the patient attained competent self-care and an enhanced quality of
      life. Characteristics of effective collaboration are described. Replication of
      this design by psychiatric clinical nurse specialists is recommended.

PMID- 8561514
TI  - Elders' perceptions of the role of group psychotherapy in fostering self
      transcendence.
AB  - Psychotherapeutic goals and interventions for older adults, like those for
      children and other age groups, need to be developmentally appropriate. Past
      clinical research has shown that self-transcendence is a resource for mental
      health in later life. The effectiveness of group psychotherapy in facilitating
      self-transcendence in elders was examined, applying a method of analysis in which
      a small, intact clinical sample could be used to generate data for research
      purposes. Results, based on a matrix analysis of group members' perceptions,
      indicated that group psychotherapy enhanced self-transcendence in various ways.
      Group psychotherapy may be used not only as a cost-effective treatment modality,
      but also as a theory-based intervention that is developmentally-appropriate for
      elders.

PMID- 8561515
TI  - Educating nurses for primary psychiatric care: a South African perspective.
AB  - This article examines the meaning of Primary Health Care, and the implications
      for the provision of psychiatric care at this level. The authors describe how one
      nursing school in a developing country, South Africa, prepares nurses to function
      in a primary health care system, which fully includes psychiatric care. The
      results for the service, the community and the students are described.

PMID- 8561516
TI  - Potential for intergenerational conflict in Cuban and Haitian immigrant families.
AB  - A descriptive survey of 30 Cuban and 30 Haitian immigrant mothers describes and
      differentiates the families within the two cultural groups on: (a)
      sociodemographic characteristics; (b) concepts of children; and (c) childrearing
      beliefs and practices related to independence training, sex role development, and
      discipline patterns. Results indicate the two groups have similar
      sociodemographic characteristics but differ on qualities admired in boys and
      girls, career expectations held for their children, social autonomy allowed male
      and female children, and methods used to instill proper sex role behavior.
      Findings suggest the existing potential for intergenerational conflict in
      families within immigrant groups whose language and cultural beliefs differ from
      those of the culture into which they have entered and are acculturating.
      Implications for care indicate a need for psychiatric mental health nurse (PMH
      nurses) to use the principles of cultural brokerage for intervention in and
      prevention of intergenerational conflict. Emphasis is placed on the development
      of transcultural interventions designed to empower immigrant parents to address
      the real or perceived conflicting childrearing beliefs and practices held between
      their original culture and the culture into which they are acculturating.

PMID- 8561517
TI  - Integrating esthetics into nursing: literature as a suggested modality.
AB  - In this article the author argues for the importance of reintegrating the
      neglected pattern of esthetics into the teaching and practice of nursing.
      Approaching art as both a means and end, the essay illustrates, how art can
      inform the specialty. By exposure to selected literary works, nurses can
      vicariously achieve understanding of human conditions that they could not
      otherwise experience. Through the art act, nurses can examine the depths of their
      interventions, identify them, and creatively center themselves. Integrating
      esthetics into nursing education and collaborating with colleagues in the field
      of humanities can invigorate a discipline in search of identity and justification
      during a time of professional turbulence.

PMID- 8561518
TI  - The chemotherapy of rodent malaria. L. The activities of some synthetic 1,2,4
      trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part
      3: Observations on 'Fenozan-50F', a difluorinated 3,3'-spirocyclopentane 1,2,4
      trioxane.
AB  - A novel difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane ('Fenozan-50F') is a
      potent blood schizontocide against drug-sensitive and drug-resistant rodent
      malaria parasites. It also exerts some action against pre-erythrocytic
      schizogony, is a potent gametocytocide, and exerts a direct sporontocidal effect
      in infected mosquitoes. In the '4-day test' the ED90s are 6.8 and 6.0 mg/kg/day
      for four consecutive days by the subcutaneous and oral routes respectively
      against drug-sensitive Plasmodium berghei N, and 6.3 and 25 mg/kg against
      chloroquine-resistant P. yoelii NS in vivo. By the oral route against P. berghei
      N infection in mice, Fenozan-50F is about half as active as arteether but nearly
      three times as active as sodium artesunate. The activity of Fenozan-50F is
      retained against a wide spectrum of drug-resistant parasite lines, although those
      highly resistant to quinine or to artemisinin are less responsive at the ED90
      level. At the ultrastructural level the compound, when administered to infected
      mice, causes marked changes in the membranes and ribosomes of trophozoites and
      young schizonts and of immature gametocytes, although few changes are apparent in
      mature gametocytes. Its toxicity appears to be very low when it is administered
      to mice by either the oral or subcutaneous route. Fenozan-50F is considered to be
      a good candidate for eventual use as a therapeutic agent for infection with
      polyresistant malaria in man.

PMID- 8561519
TI  - Malaria in a rural area of Sierra Leone. I. Initial results.
AB  - Malaria surveys to collect base-line data for an intervention study was carried
      out in a rural, high rainfall area of West Africa. Methods for the different
      components of the study are described. A mortality survey, using verbal autopsy
      questionnaires, established an infant mortality rate of 74/1000 live births/year,
      a child mortality rate of 25/1000/year and a mortality rate for children under
      five years of 36/1000/year. The most common causes of death were malaria and
      malnutrition. The results of two clinical surveys showed that the prevalence of
      illness in nought to seven-year-olds increased from 30% at the pre-rains survey
      to 58% at the post-rains survey. The most significant increases were a three-fold
      increase in the prevalence of upper respiratory infections, whilst skin and eye
      infections and fever rates doubled. A knowledge, attitudes and practice survey of
      210 heads of households or women of child-bearing age revealed that 76% had never
      had any formal education. Eighty-nine per cent recognized that there was a
      malaria problem in the area, but only 30% knew that mosquitoes were involved in
      its transmission, and only half of the respondents were aware that malaria was
      preventable.

PMID- 8561521
TI  - Waking electroencephalograms in the blood-lymph and encephalitic stages of
      gambian trypanosomiasis.
AB  - Waking electroencephalograms (EEG) were recorded from 48 patients infected with
      Trypanosoma gambiense. The EEG of the 10 patients with blood-lymph involvement
      were indistinguishable from those of healthy controls but recordings from the 38
      patients with the encephalitic phase of the disease showed three unusual
      profiles. One profile type, apparently indicative of early cerebral impairment,
      had a sustained low-voltage background similar to that seen during light sleep. A
      second profile type, seen in cases with acute cerebral involvement but without
      focal seizures, showed paroxystic waves. The third unusual EEG pattern was of
      various types of delta wave (similar to those seen in demyelinating encephalitis)
      and rapid, intermittent high-voltage delta bursts between periods of lower
      voltage delta activity (as often seen in meningo-encephalitis); all types of
      delta wave were of higher voltage than the spike and wave complexes. Although no
      definite correlation has been established between the severity of the disease,
      the results of clinical tests, and waking EEG patterns, it appears that the three
      types of EEG profile are indicative of the degree of cerebral involvement.

PMID- 8561520
TI  - Malaria in a rural area of Sierra Leone. II. Parasitological and related results
      from pre- and post-rains clinical surveys.
AB  - The prevalence of Plasmodium falciparum in a cohort of over 900 nought to seven
      year-old children living in a rural area of Sierra Leone was found to be
      approximately 61%, both before and after the rainy season. Plasmodium malariae
      rates measured in the same children were approximately 12%, and P. ovale rates
      averaged about 1%. Spleen rates averaged 44% for the two surveys; the age
      prevalence spleen profiles closely matched those for P. falciparum. The overall
      gametocyte rates for both P. falciparum and P. malariae were roughly one fifth of
      the prevalence rates for the asexual parasites. However, whilst there was no
      difference between the P. falciparum gametocyte rates at the two surveys, the P.
      malariae rate was significantly higher post-rains when compared with the pre
      rains result. Spleen size did not increase with increased parasite density. There
      was a statistically significant difference between the geometric mean P.
      falciparum trophozoite densities of febrile and afebrile children both before and
      after the rainy season, but there was little seasonal difference in the means for
      the febrile children or in those for the afebrile children. Antimalaria antibody
      levels, measured by ELISA and IFAT, showed no significant differences at either
      survey. The levels found were high for all age groups, indicating that exposure
      to malaria begins at birth. Our results indicate that, in the area studied,
      malaria is hyperendemic and is probably transmitted perennially.

PMID- 8561522
TI  - Visceral leishmaniasis in Ethiopia. I. Cross-sectional leishmanin skin test in an
      endemic locality.
AB  - A cross-sectional leishmanin skin test was carried out on a sample population of
      730 individuals. The overall prevalence of leishmanin positivity was 36.4%; 50.9%
      of males and 23.2% of females showed positive skin test reaction. The skin-test
      profile in the study area is typical of an endemic focus of visceral
      leishmaniasis. The increase in leishmanin positivity with age parallels the age
      specific disease profile and indicates an outdoor exposure to infection.

PMID- 8561523
TI  - Visceral leishmaniasis in Ethiopia. II. Annual leishmanin transformation in a
      population. Is positive leishmanin reaction a life-long phenomenon?
AB  - A one-year follow-up leishmanin skin test was undertaken in 605 subjects aged
      five years and above. The point prevalence of leishmanin positivity in the
      selected age group was 46.8%; 62.5% of the males and 32.1% of the females showed
      positive leishmanin reactions. The annual incidence of skin test transformation
      was 14.8%. In this study, positive to negative leishmanin conversion was noted in
      9.3% of study subjects with initial positive leishmanin reaction.

PMID- 8561525
TI  - Use of murine subinoculation for the diagnosis and isolation of toxoplasmosis in
      HIV-infected patients with persistent lymphadenopathy.
AB  - A murine model was used to try to elucidate the importance of Toxoplasma gondii
      infection in HIV-positive patients. Laboratory mice were inoculated with lymph
      node homogenates or buffy coats from 30 HIV-infected individuals with persistent
      lymphadenopathy. Sabin and Feldman dye-tests, direct agglutination tests and
      indirect immunofluorescence assays (IFA) of serum samples taken from the mice six
      weeks after inoculation indicated, respectively, that 26.6%, 43.4% and 33.3% of
      the lymph node inocula and 13.3%, 30.0% and 16.7% of the buffy coat samples had
      been Toxoplasma-positive. Histological examination of the brains of the infected
      mice revealed Toxoplasma tachyzoites or bradyzoites in the mice given buffy coat
      samples from one patient (3.3%) and those given lymph node material from three
      patients (10%). No protozoa were found in the brains of the control mice, all of
      which were sero-negative. In contrast to the mouse results, other, concurrent
      tests failed to detect any signs of toxoplasmosis infection in the patients,
      except relatively low titres of anti-Toxoplasma antibodies in 11 patients, even
      though two patients developed brain toxoplasmosis, one 12 and the other 18 months
      after the study. It appears, therefore, that an animal model can be very useful
      in the diagnosis of toxoplasmosis in HIV patients.

PMID- 8561524
TI  - Activity of a new oxadiazole compound, against experimental infections with
      Entamoeba histolytica and Giardia lamblia in animal models.
AB  - BTI 2286E(+/-)-E-3-(4-methylsulphinylstyryl)-1,2,4-oxadiazole has demonstrated
      potent amoebicidal activity in a single-dose treatment against Entamoeba
      histolytica infection in the livers of golden hamsters and the caeca of mice,
      hamsters and rats. It has intra luminal activity against Entamoeba criceti, a
      natural infection in golden hamster, and anti-giardial activity against Giardia
      lamblia infection in suckling mice. BTI 2286E is more potent than metronidazole
      in extra intestinal, intra luminal amoebiasis models and has significant
      advantages in that it is non-mutagenic in the Ames test and has a shorter
      duration of effective treatment.

PMID- 8561526
TI  - A community-based randomized trial of praziquantel to control schistosomiasis
      morbidity in schoolchildren in Zambia.
AB  - A community-based, double-blind, randomized trial of praziquantel was carried out
      in an area of Zambia endemic for schistosomiasis. The aim of the study was to
      assess the impact of the treatment on Schistosoma mansoni morbidity. A total of
      377 infected children, aged seven to 19 years, was randomized into two groups:
      one of 190 (group A) and one of 187 (group B). All children were treated with 40
      mg praziquantel/kg at the start of the study. Six months later, the children in
      group A were re-treated with the same dose of praziquantel, while the children in
      group B were given placebos. All children were followed up three, six and 12
      months after the initial treatment, morbidity being clinically evaluated at the
      six- and 12-month follow-ups. The results show that, in both groups of children,
      there were significant reductions in splenomegaly, hepatomegaly, and subjective
      symptoms of morbidity six and 12 months after initial treatment. However, there
      were no significant differences, between the two groups, in the prevalences of
      these symptoms of morbidity. It therefore appears that once-yearly treatment of
      children, in this and similar endemic areas, is sufficient to reduce
      schistosomiasis morbidity to, and maintain it at, a tolerable level.

PMID- 8561527
TI  - Immunodiagnosis of dracunculiasis by dot-ELISA.
AB  - A dot-enzyme-linked immunosorbent assay (dot-ELISA) using soluble adult
      guineaworm antigen was developed for immunodiagnosis of Dracunculus medinensis
      infection. The test was found to be specific and sensitive when compared with
      ELISA. The dot-ELISA described here was found to be time-saving and easy to
      perform, and its possible use as a diagnostic and epidemiological tool under
      field conditions is therefore discussed.

PMID- 8561528
TI  - Toxocara eggs in the soil of public places and schools in Basrah, Iraq.
AB  - One hundred and eighty soil samples were collected from public places and school
      yards in urban and rural areas in Basrah between October 1991 and March 1992.
      Each sample was examined by zinc sulphate flotation and sedimentation. Toxocara
      eggs were found in 22 samples (12.2%). Of the recovered positive samples 10
      contained viable and fully embryonated eggs. Viable eggs were observed in higher
      proportions of soils collected from the surroundings of Basrah slaughter-house,
      where there are large numbers of dogs and cats. The observed mean number of eggs
      per 5 g of soil was 2.8 +/- 1.9 S.D. The contamination rate in urban areas
      (17.3%) was significantly higher (P < 0.05) than that in rural areas (6.1%).
      Thirteen of 116 samples (11.2%) collected from public places and nine of 64
      samples (14.1%) from school yards contained Toxocara eggs. Urban public places
      and schools have higher contamination rates (18.0% and 16.2%, respectively) than
      those in rural areas (3.6% and 11.1%), but the differences are significant (P <
      0.05) between public places only.

PMID- 8561529
TI  - Phlebotomine sandflies of Kenya (Diptera: Psychodidae). I. The validity of
      Phlebotomus (Larroussius) elgonensis Ngoka, Madel and Mutinga.
AB  - Sandflies collected in Kitum cave on the Kenyan side of Mount Elgon were
      identified as Phlebotomus (Larroussius) elgonensis Ngoka, Madel and Mutinga, a
      species synonymized with P. (L.) aculeatus Lewis, Minter and Ashford, by D. J.
      Lewis. A comparison of the flies from Kitum cave with P. aculeatus from Lake
      Elmentaita, Kenya, shows marked differences in the lengths of: (a) the
      spermathecal ducts of the female; (b) the style, coxite, genital pump and
      aedeagus of the male; and (c) the palpal segments of both sexes. Other notable
      differences are in the shape of the base of the spermathecal ducts; the position
      of spines on, and the shape of, the tip of the aedeagus; and the appearance of
      the pharyngeal armatures of both sexes. Phlebotomus elgonensis is redescribed and
      it is concluded that it is sufficiently different from P. aculeatus to deserve
      recognition as a valid species.

PMID- 8561530
TI  - Theileria sergenti: experimental transmission by the long-nosed cattle louse,
      Linognathus vituli.

PMID- 8561531
TI  - Furuncular myiasis due to Cordylobia anthropophaga, endemic in the same locality
      for over 130 years.

PMID- 8561532
TI  - Look ma, no hands!

PMID- 8561533
TI  - Atrial activation during chronic atrial fibrillation in patients with isolated
      mitral valve disease.
AB  - BACKGROUND: A computerized 32-channel mapping system has been developed to
      investigate the characteristics of the atrial activation sequence. The system is
      capable of displaying sequential atrial maps and provides a rapid and dynamic
      means of verifying the activation sequence of atrial fibrillation. METHODS: Using
      this system, we performed intraoperative atrial activation mapping in 10 patients
      with chronic atrial fibrillation who were undergoing isolated mitral valve
      operations. RESULTS: Regular and repetitive activation (cycle length ranged from
      131 to 228 milliseconds) originated in the left atrium in all 10 patients. Two
      patterns of repetitive activation in 2 patients and three patterns in 1 patient
      appeared alternately during the observation period in the left atrium. In
      contrast to the repetitive activation in the left atrium, the activation sequence
      of the right atrium was extremely complex and chaotic. In 7 of the 10 patients,
      the same pattern of right atrial activation was never repeated during the
      observation period. In 2 patients, revolution of repetitive activation in the
      right atrium sporadically appeared, but the pattern of activation immediately
      deteriorated to a complex and chaotic pattern. In 1 patient, repetitive
      activation emerged from the low lateral portion of the right atrium. Because our
      mapping technique was limited by the number of available atrial electrodes,
      discrete reentrant circuits or ectopic foci could not be demonstrated in the
      present study. However, the activation sequences during chronic atrial
      fibrillation suggested that (1) the left atrium would act as an electrical
      driving chamber for atrial fibrillation in the majority of the patients and (2)
      atrial activation patterns are different in each case. CONCLUSIONS: Computerized
      intraoperative mapping should guide surgeons in determining the appropriate
      surgical procedure and facilitate operation for chronic atrial fibrillation
      associated with mitral valve disease.

PMID- 8561534
TI  - Effect of nitroglycerin on spinal cord ischemia after thoracic aortic cross
      clamping.
AB  - BACKGROUND: Thoracic aortic cross-clamping with the use of sodium nitroprusside
      (SNP) has been shown to cause a decrease in spinal cord perfusion pressure and an
      increased incidence of paraplegia. Nitroglycerin is frequently used in this
      setting. This study investigated the effects of nitroglycerin and SNP on spinal
      cord ischemia. METHODS: Three-groups of 8 mongrel dogs underwent thoracic aortic
      cross-clamping for 45 minutes. Proximal pressure was maintained between 95 and
      100 mm Hg with SNP, nitroglycerin, or phlebotomy. All animals were neurologically
      evaluated 24 hours later by a blinded observer, and the findings were confirmed
      by histopathologic study. Statistical analysis (p value of less than 0.05) of
      measured hemodynamic data was by analysis of variance and of Tarlov scores, the
      Mann-Whitney U test. RESULTS: Distal aortic pressures (p < 0.001), Tarlov scores,
      and spinal cord perfusion pressures (p < 0.01 and p < 0.05 for SNP group and
      nitroglycerin group, respectively) were significantly higher in the phlebotomy
      group compared with the SNP and NTG groups. Cerebrospinal fluid pressures were
      significantly lower in the phlebotomy group compared with the SNP group (p <
      0.001). CONCLUSIONS: The use of either NTG or SNP was associated with a high
      incidence of paraplegia. Nitroglycerin appears to be no safer than SNP when used
      during thoracic aortic cross-clamping.

PMID- 8561535
TI  - Effects of cardiopulmonary bypass temperature on pulmonary gas exchange after
      coronary artery operations.
AB  - BACKGROUND: Pulmonary dysfunction is one aspect of the postoperative morbidity
      associated with cardiopulmonary bypass. Normothermic systemic perfusion can
      result in shorter intubation times, which have been attributed to improved
      pulmonary gas exchange, but the influence of perfusion temperature on pulmonary
      gas exchange itself is not known. METHODS: Pulmonary gas exchange was assessed
      using alveolar-arterial oxygen pressure gradients in 45 patients undergoing
      routine coronary revascularization who were randomized to undergo cardiopulmonary
      bypass at 28 degrees C, 32 degrees C, or 37 degrees C. This was part of a more
      comprehensive study of the effects of temperature on bodily systems. The
      gradients were estimated preoperatively with the patients breathing air, again
      over a period between 2 and 4 hours postoperatively during mechanical ventilation
      with three different oxygen concentrations (30%, 40%, and 60%), and again 1 hour
      after extubation while breathing the same three oxygen concentrations. RESULTS:
      Preoperative alveolar-arterial oxygen pressure gradients on air were 24.4 +/- 8.2
      mm Hg (mean +/- standard deviation) (28 degrees C), 24.5 +/- 20.4 mm Hg (32
      degrees C), and 20.5 +/- 9.5 mm Hg (37 degrees C). Postoperatively, during
      ventilation and after rewarming, the gradients increased with the increase in
      inspired oxygen fraction concentrations (30% to 60%) from 67.1 +/- 12.0 mm Hg to
      193.1 +/- 30.5 mm Hg (28 degrees C), from 76.4 +/- 20.6 mm Hg to 246.7 +/- 47.7
      mm Hg (32 degrees C), and from 79.0 +/- 18.0 mm Hg to 222.9 +/- 40.5 mm Hg (37
      degrees C), respectively. A similar pattern was noted 1 hour after extubation,
      when the gradients increased from 72.4 +/- 12.5 mm Hg to 256.6 +/- 26.5 mm Hg (28
      degrees C), from 75.7 +/- 13.9 mm Hg to 252.7 +/- 38.3 mm Hg (32 degrees C), and
      from 69.1 +/- 19.3 mm Hg to 253.1 +/- 33.0 mm Hg (37 degrees C). There were no
      significant differences in alveolar-arterial oxygen pressure gradient between the
      three groups during ventilation or after extubation. CONCLUSIONS: Cardiopulmonary
      bypass perfusion temperature does not influence alveolar-arterial oxygen pressure
      gradients in the first 12 hours after routine coronary artery bypass grafting in
      patients with uncompromised pulmonary and left ventricular function.

PMID- 8561536
TI  - Volume requirements for cardiac surgery credentialing: a critical examination.
      The Ad Hoc Committee on Cardiac Surgery Credentialing of The Society of Thoracic
      Surgeons.
AB  - New volume requirements for coronary artery bypass grafting are being imposed on
      cardiac surgeons by hospitals, managed care groups, and others. The rationale for
      this is unclear. The available literature as well as additional sources relating
      volume and outcomes in cardiac surgery were extensively reviewed and reexamined.
      There are no data to conclusively indicate that outcomes of cardiac operations
      are related to a specific minimum number of cases performed annually by a cardiac
      surgeon. Each cardiothoracic surgeon should participate in a national database
      that permits comparison of his or her outcomes on a risk-adjusted basis with
      other surgeons. Until conclusive data become available that link volume to
      outcome, volume should not be used as a criterion for credentialing of cardiac
      surgeons by hospitals, managed care groups, or others. Instead, each surgeon
      should be evaluated on his or her individual results.

PMID- 8561537
TI  - Morphometric analysis of the right gastroepiploic artery and the internal mammary
      artery.
AB  - BACKGROUND: The internal mammary artery (IMA) and the right gastroepiploic artery
      (RGEA) are frequently used as conduits for coronary artery bypass grafting.
      METHODS: Morphometric measurements and histologic characteristics of the RGEA and
      the IMA were studied in 25 patients undergoing coronary artery bypass grafting.
      RESULTS: External radius was found to be more in the IMA (range, 18 to 56
      microns; mean, 39.56 microns) in comparison with the RGEA (range, 24 to 51
      microns; mean, 32.52 microns; p < 0.01). There was no significant difference
      between the vessels in intimal thickness (IMA: 0.0 to 0.25 micron; mean, 0.05
      micron; RGEA: 0.0 to 0.28 micron; mean, 0.09 micron), internal radius (IMA: 5 to
      47 microns; mean, 28.40 microns; RGEA: 16 to 42 microns; mean, 23.56 microns),
      area of media (IMA: 1,690 to 3,476 microns2; mean, 2,777.52 microns2; RGEA: 1,659
      to 3,600; mean, 3,012.44 microns2), intimal thickening index (IMA: 0.0 to 0.02;
      mean, 0.01; RGEA: 0.0 to 0.13; mean, 0.01), and medial index (IMA: 0.14 to 0.60;
      mean, 0.36; RGEA: 0.18 to 0.63; mean, 0.39). Histologic examination of the RGEA
      showed more defects in continuity of internal elastic lamina and rich smooth
      muscle cells in the media. CONCLUSIONS: There was no difference in the
      morphometric measurements of the IMA and the RGEA except external radius, which
      was greater for the IMA. The histologic differences found in the RGEA may
      indicate an increased propensity for atherosclerosis of the RGEA as compared with
      the IMA. Some concern regarding the long-term patency of the RGEA in myocardial
      revascularization is warranted.

PMID- 8561538
TI  - Randomized study of right ventricular function with intermittent warm or cold
      cardioplegia.
AB  - BACKGROUND: Transient right ventricular dysfunction has been previously
      documented after bypass operations despite adequate myocardial protection with
      intermittent antegrade cold blood cardioplegia. Recently warm blood cardioplegia
      has been interrupted during construction of distal anastomoses to improve
      visualization. The effects of intermittent antegrade warm blood cardioplegia, and
      the resultant periods of right ventricular normothermic ischemia, on
      postoperative right ventricular function are unknown. METHODS: To assess the
      effects of cardioplegia on right ventricular protection, 52 patients undergoing
      isolated bypass grafting were randomized to intermittent warm or cold blood
      cardioplegia. The two groups were similar with respect to age, sex, ventricular
      function, and right coronary stenoses. Cross-clamp times were similar (warm, 64
      +/- 22 minutes; cold, 63 +/- 15 minutes; not significant). The cumulative time of
      cardioplegia interruption was longer in the cold group (42 +/- 8 minutes) than in
      the warm group (31 +/- 14 minutes; p < 0.002). A rapid-response thermodilution
      catheter was employed to assess postoperative right ventricular ejection fraction
      and end-diastolic and end-systolic volume indices. RESULTS: The right ventricular
      ejection fraction was greater in the warm group at 6 hours (warm, 0.46 +/- 0.06;
      cold, 0.37 +/- 0.08; p < 0.05) and 8 hours (warm, 0.43 +/- 0.08; cold, 0.37 +/-
      0.08; p < 0.05) postoperatively. The right ventricular end-diastolic volume index
      was less in the warm group 8 hours postoperatively (warm, 83 +/- 11 mL/m2; cold,
      94 +/- 16 mL/m2; p < 0.05). There were no differences in pulmonary arterial
      pressures or right ventricular stroke work index. CONCLUSIONS: Despite
      intermittent normothermic ischemia of half the cross-clamp time, patients
      receiving warm cardioplegia maintained right ventricular hemodynamics after
      bypass grafting.

PMID- 8561539
TI  - Minimally invasive coronary artery bypass grafting.
AB  - BACKGROUND: Standard options for the invasive management of proximal disease of
      the left anterior descending coronary artery include coronary artery bypass
      grafting with a left internal mammary artery and percutaneous transluminal
      coronary angioplasty. METHODS: We describe a surgical technique for bypass of the
      left anterior descending coronary artery with a left internal mammary artery
      without median sternotomy and without cardiopulmonary bypass. Thoracoscopy is
      used to harvest the internal mammary artery, whereas the mammary-coronary artery
      anastomosis is performed under direct vision through a limited anterior
      thoracotomy. RESULTS: We have performed this procedure successfully in 3 patients
      with minimal morbidity and shortened hospital stay. Average operative time was 3
      hours and postoperative hospital stay averaged less than 48 hours. CONCLUSION:
      Although experience is limited and follow-up is very short, with further
      experience, this less invasive surgical technique may become a viable option for
      the management of proximal left anterior descending disease.

PMID- 8561540
TI  - Association of latissimus dorsi muscle expansion with electrostimulation before
      cardiomyoplasty.
AB  - BACKGROUND: The principle of cardiomyoplasty is chronic electrostimulation of the
      latissimus dorsi muscle (LDM) flap wrapped around the heart to obtain a phasic
      activity that can be integrated to ventricular kinetics. In clinical
      cardiomyoplasty procedures, a complete wrap of both ventricles by the LDM cannot
      always be obtained in cases of extremely dilated hearts. This is due to the
      limited LDM length available for wrapping. In most of these cases, benefits of
      cardiomyoplasty are very limited. We have investigated the feasibility of
      progressive LDM expansion associated with electrostimulation. The aim was to
      increase the muscle area before cardiomyoplasty, while preserving the
      electrophysiologic characteristics of muscle fibers. METHODS: In 5 goats, a
      silicone LDM expander with two incorporated muscular pacing electrodes was
      inserted deep into the LDM through a paravertebral incision along the posterior
      edge of the muscle. The pacing leads were connected to a myostimulator implanted
      in a subcutaneous pocket. The expander was progressively inflated over 8 weeks,
      up to 500 mL. Simultaneously the LDM was electrostimulated. RESULTS: At 2 months
      planimetric studies demonstrated an increase of the LDM surface from 175 +/- 12
      to 229 +/- 17 cm2 (+31% +/- 4%; p < 0.05). The expanded LDM showed preserved
      electrophysiologic characteristics. The analysis of biopsy samples revealed
      histologic integrity of muscle fibers and preservation of their mean diameter.
      CONCLUSIONS: Potential benefits of this procedure are (1) increase of muscle
      surface, (2) training of muscular fibers and preservation of muscular tone, and
      (3) division of the distal vascular supply at implantation, which may potentiate
      vascularization from the LDM main pedicle. An LDM expansion could be considered
      before cardiomyoplasty in cases of significant heart dilatation. This device was
      successfully implanted in 2 patients, 2 months before cardiomyoplasty.
      Cardiomyoplasties were performed without difficulty, and a complete biventricular
      wrap was obtained in both patients in spite of massive cardiomegaly.

PMID- 8561541
TI  - Reduced prostacyclin and increased leukotriene B4 synthesis in porcine venous
      arterial grafts.
AB  - BACKGROUND: Migration and proliferation of vascular smooth muscle cells in the
      intima and superimposed atheroma are the main changes underlying late failure of
      saphenous vein bypass grafts. There is evidence that these events are partly
      modulated by complex interactions between inhibitors of vascular smooth muscle
      cell proliferation, such as prostacyclin (PGI2), and mitogens, such as
      leukotriene B4 (LTB4). Because the relative balance between these eicosanoids may
      play a role in vein graft failure, the synthesis of PGI2 and LTB4 was measured in
      porcine saphenous vein-carotid artery grafts 4 weeks after implantation and
      compared with ungrafted vein and common carotid artery from the same animal.
      METHODS: Vessels were cut into 2-mm squares and preincubated in Dulbecco's
      minimum essential medium for 4 hours at 37 degrees C. Tissues were then further
      incubated with Dulbecco's minimum essential medium containing a range of
      concentrations of noradrenaline, arachidonate, and calcium ionophore A23187.
      Release of PGI2 and LTB4 into the supernatant was then assessed by
      radioimmunoassay. RESULTS: In response to all stimulators, PGI2 release was
      markedly diminished in vein grafts compared with ungrafted saphenous veins and
      carotid arteries. The patterns of responses were similar in each vessel type. In
      contrast, LTB4 release was significantly enhanced in vein grafts compared to
      ungrafted saphenous veins and carotid arteries. CONCLUSIONS: These data indicate
      that there is a down-regulation of cyclooxygenase or PGI2 synthase in porcine
      vein grafts, which may constitute a further phenotypic change that would augment
      the hyperplastic process. Local increases in LTB4 synthesis in the vein graft,
      which indicates an induction of lipoxygenase and LTB4 synthase enzymes (and
      possibly reflects release from leukocytes which have infiltrated the graft), may
      contribute to increased intimal proliferation by direct promitogenic effects on
      smooth muscle cells.

PMID- 8561542
TI  - Endarterectomy for calcified porcelain aorta associated with aortic valve
      stenosis.
AB  - BACKGROUND: A calcified porcelain aorta may complicate aortic valve insertion and
      require an alternative, more complex method for valve replacement. The reason for
      this is that sutures cannot be inserted through the calcific plates in the
      annulus and ascending aorta. METHODS: In 6 patients with an average age of 73.8
      years (range, 65 to 81 years), we performed the simpler procedure of aortic
      endarterectomy of the calcific plates with the aortic valve replacement. We
      realized that there may be an increased risk of postoperative complications,
      particularly stroke. The calcific plates were fractured to allow debridement of
      the calcium. In addition, an end-arterectomy was performed of the left main
      coronary ostium in 2 patients, and 5 patients also had coronary artery bypass
      grafting performed. RESULTS: All 6 patients underwent successful operations
      without major complications. On follow-up, echocardiography or computed
      tomographic scans in 3 patients have not shown dilation of the ascending aorta.
      CONCLUSION: Endarterectomy of the aorta may be an option in the management of
      patients with calcification of the aorta.

PMID- 8561543
TI  - Prospective study of quality of life before and after open heart operations.
AB  - BACKGROUND: The aim of this prospective study, with completion of questionnaires
      before and 3 months after open heart operations, was to evaluate the improvement
      of quality of life brought about by these operations and the predictors of this
      improvement. METHODS: The Nottingham health profile questionnaire contains 38
      subjective statements divided into six sections: energy, physical mobility,
      emotional reaction, pain, sleep, and social isolation. Factors influencing
      quality of life scores were determined by analysis of covariance. Factors
      influencing the status of the patients (improved or worsened) were determined by
      logistic regression. RESULTS: From January to July 1994, 215 consecutive patients
      underwent elective open heart operations. The comparison between mean
      preoperative and postoperative scores showed an improvement in all sections of
      quality of life. An average of 80% of patients were improved by their operations.
      Independent predictors of less improvement of quality of life scores were as
      follows: for the energy section, age over 70 and New York Heart Association
      functional class III or IV; for sleep, age over 70; for physical mobility, New
      York Heart Association functional class III or IV; for social isolation, female
      gender; and for pain, age over 70 and abnormal segmental wall motion. Independent
      predictors of patients worsened by operation were as follows: New York Heart
      Association functional class III or IV in the energy section (odds ratio = 3.7,
      95% confidence interval 1.4 to 9.8) and in the physical mobility section (odds
      ratio = 2.4, 95% confidence interval 1.02 to 5.5), female gender in the social
      isolation section (odds ratio = 2.8, 95% confidence interval 1.03 to 7.7), and
      presence of at least one comorbid disease in the emotional reaction section (odds
      ratio = 2.5, 95% confidence interval 1.17 to 5.2). CONCLUSIONS: Cardiac
      operations improve quality of life in patients. The improvement is similar for
      patients undergoing coronary artery bypass grafting versus valve replacement, and
      for patients with no postoperative events versus those with nonlethal
      postoperative complications. The strongest predictive factors for quality of life
      are age and New York Heart Association functional class.

PMID- 8561544
TI  - Excellent survival in a subgroup of patients with intrapulmonary metastasis of
      lung cancer.
AB  - BACKGROUND: Recently, intrapulmonary metastases in non-small cell lung cancer
      have been considered to have less influence on prognosis than extrapulmonary
      metastases. We report a subgroup found among patients with intrapulmonary
      metastases showing a good prognosis. METHOD: A retrospective study was performed
      on 236 consecutive patients with non-small cell lung cancer who underwent
      surgical resection of their tumors. Intrapulmonary metastases were found
      histopathologically in 50 of them, and their clinicopathologic features were
      investigated. RESULTS: Analysis of postsurgical results revealed a subgroup of
      patients showing excellent prognosis (n = 15). They had well-differentiated
      adenocarcinomas with bronchioloalveolar spread and pT1-2 N0, without vascular or
      lymphangitic invasion. Their actuarial 5-year survival rate was 100%, with a mean
      survival interval to date of 28 months. However, none of the other 35 patients
      survived for 5 years, with a mean survival interval to date of 11 months.
      CONCLUSIONS: We have clarified that patients with histopathologically diagnosed
      intrapulmonary metastases from non-small cell lung cancer do not constitute a
      homogeneous group. Pulmonary metastases with good prognosis, which are considered
      to be hematogenous metastases, may be benign lesions such as adenomatous or
      atypical adenomatous hyperplasias mimicking malignant tumors.

PMID- 8561545
TI  - In vitro study of ablated lung tissue in Nd:YAG laser irradiation.
AB  - BACKGROUND: Neodymium:yttrium-aluminum garnet lasers are used to reduce lung
      volume. An assessment of the relationship between the histologic and gross
      findings in the lung irradiated by a laser would be helpful in laser-assisted
      pneumoplastic procedures. METHODS: In vitro lung lobes surgically resected for
      pulmonary carcinomas were irradiated with a neodymium:yttrium-aluminum garnet
      laser at three energy levels in three modes: contact rubbing, contact pointing,
      and noncontact. Pleural degeneration in 216 samples from 24 lobes was classified
      as coagulative, amorphous, or destructive. At all energy levels, the laser was
      applied for 1.5 seconds. RESULTS: Noncontact mode at 7.5 W or 15 W and contact
      rubbing at 5 W caused coagulative or amorphous degeneration but no destructive
      degeneration. The energy level correlated with the color of the degenerated
      pleura. The incidence of destructive pleural degeneration, which led to air leaks
      as revealed by an air inflation test, was 0% in pink and white samples, 59% in
      brown samples, and 100% in black samples (p < 0.0001, white versus brown
      samples). CONCLUSIONS: In neodymium:yttrium-aluminum garnet laser ablation of
      lung tissue, the color of the degenerated pleura correlates with the intensity of
      the applied laser energy and the degree of pleural degeneration.

PMID- 8561547
TI  - Diaphragmatic paralysis: a complication of lung transplantation.
AB  - BACKGROUND: Damage to the phrenic nerve, either unilaterally or bilaterally, is a
      well-documented complication of cardiac operation, but less commonly reported
      after lung transplantation. METHODS: A retrospective review of 185 single and
      sequential single lung transplant procedures was performed at The Toronto
      Hospital. Objective confirmation (fluoroscopy or ultrasound) of diaphragmatic
      paralysis was found in 6 patients. Paralysis was unilateral in 5 patients (all
      were left sided) and bilateral in 1 patient. RESULTS: The average length of
      ventilation was 8.2 +/- 9.2 days with an average intensive care unit stay of 11.2
      +/- 10.6 days. Mean duration in the hospital was 37.5 +/- 11.1 days. The average
      length of intensive care unit stay and hospitalization were compared with all
      other sequential single transplantations performed from approximately the time of
      the first documented case of diaphragmatic paralysis. Intensive care unit stay
      and hospitalization for the other (no diaphragmatic paralysis) transplant
      recipients were significantly shorter (5.3 +/- 2.7 and 29.1 +/- 12.9 days,
      respectively; p < 0.05). One patient required noninvasive ventilatory assistance
      via bilevel positive airway pressure in the hospital. One other patient used
      bilevel positive airway pressure in the hospital and overnight for 6 months after
      discharge. All patients obtained acceptable lung function and were ambulatory
      upon discharge from the hospital. CONCLUSIONS: Clinically detectable
      diaphragmatic paralysis is an infrequent complication of lung transplantation and
      is associated with longer intensive care unit stay and hospitalization, but is
      not associated with significant adverse outcomes.

PMID- 8561546
TI  - No continuous relationship between Veterans Affairs hospital coronary artery
      bypass grafting surgical volume and operative mortality.
AB  - BACKGROUND: The purpose of this study was to determine whether risk-adjusted
      coronary artery bypass grafting mortality rates are significantly related to
      coronary artery bypass grafting surgical procedure volume within the Department
      of Veterans Affairs hospital system. METHODS: From April 1987 to September 1992,
      expected mortality rates were calculated for 23,986 coronary artery bypass
      grafting procedures performed at 44 different Veterans Affairs hospitals.
      RESULTS: This study found a statistically significant relationship between annual
      hospital coronary artery bypass grafting volume and observed mortality rates (p <
      0.02). However, no statistically significant relationship between coronary artery
      bypass grafting volume and risk-adjusted operative mortality was found (p =
      0.10). Using analysis of variance on hospital-level data, hospitals with 100 or
      less cases per year have higher observed to expected mortality ratios than
      hospitals performing more than 100 cases per year (p = 0.03). Using Poisson
      regression models, however, a volume threshold could not be found. CONCLUSIONS:
      These findings are consistent with the current Veterans Affairs policy
      requirements to periodically review quality at low-volume hospitals.

PMID- 8561548
TI  - Unsuspected lung cancer found in work-up for lung reduction operation.
AB  - BACKGROUND: Lung reduction surgery is gaining acceptance in the treatment of
      patients suffering from severe diffuse emphysema. At the University of Pittsburgh
      210 patients have been evaluated and 128 patients have undergone lung reduction
      operations. METHODS: Ten patients, representing 7.8% of the operated group, have
      had asymptomatic cancerous or neoplastic lesions diagnosed on preoperative
      evaluation or pathologic analysis of resected tissue. RESULTS: Six primary lung
      cancers (three squamous, three adenocarcinoma) and four other neoplastic lesions
      (squamous dysplasia, chemodectoma, and two carcinoid tumorlets) have been
      identified. All patients were heavy smokers, and all had markedly impaired
      pulmonary function. Patients whose lesions were identified on preoperative
      testing underwent thoracoscopic wedge excision of the tumor alone. CONCLUSIONS:
      Our experience suggests that patients with impaired pulmonary function (chronic
      obstructive pulmonary disease) presenting for lung reduction operations are at a
      high risk of harboring an unsuspected neoplastic lesion. Complete preoperative
      evaluation of radiographic studies and preoperative bronchoscopic examination are
      mandatory.

PMID- 8561549
TI  - Detection of disseminated lung cancer cells in lymph nodes: impact on staging and
      prognosis.
AB  - BACKGROUND: A major reason for the high incidence of tumor recurrences in
      patients with apparently resectable non-small cell lung cancer is presumably
      early tumor cell dissemination, which is clearly underestimated by current
      staging procedures. METHODS: In this prospective study we assessed the frequency
      and prognostic significance of early lymphatic tumor cell spread to regional
      lymph nodes staged as tumor free by conventional histopathology by applying an
      immunohistochemical assay using monoclonal antibody Ber-Ep4. RESULTS: Ber-Ep4
      positive cells were demonstrated in 27 (21.6%) of 125 patients and in 35 (6.2%)
      of 565 lymph nodes, respectively. Immunohistochemical analysis resulted in an up
      staging in 24 of 27 patients. In patients previously staged as having pN0
      disease, tumor cells were detected in 11/70 cases (15.7%). Univariate and
      multivariate survival analysis showed that the detection of minimal nodal tumor
      cell dissemination was associated with a reduced disease-free survival (log rank
      test, p = 0.0001; Cox regression model, p = 0.001). CONCLUSIONS: The use of
      immunohistochemistry enables one to identify many patients with regional tumor
      cell dissemination at the time of operation. These patients might benefit from an
      adjuvant therapeutic regimen.

PMID- 8561550
TI  - Double-lung transplantation in the rat: an acute, syngeneic in situ model.
AB  - BACKGROUND: The high rate of reperfusion injury in clinical lung transplantation
      mandates significant improvements in lung preservation. Innovations should be
      validated using standardized and low-cost experimental models. METHODS: The model
      introduced here is analyzed by comparing global lung function after varying
      ischemic times (2, 4, 8, 16, and 24 hours). A rat double-lung block is flush
      perfused, and the main pulmonary artery and left atrium are connected to the left
      pulmonary artery and vein of a syngeneic recipient using a T-shaped stent. With
      pressure side ports and incorporated flow crystals, measurement of vascular
      resistance and graft oxygenation can be performed. The transplant is ventilated
      separately, and compliance and resistance are determined. RESULTS: The increase
      in the ischemic interval from 2 to 24 hours caused an increase in the alveolar
      arterial oxygen difference from 220 +/- 20 to 600 +/- 34 mm Hg, pulmonary
      vascular resistance from 198 +/- 76 to 638 +/- 212 mm Hg.mL-1.min-1, and
      resistance to airflow from 274 +/- 50 to 712 +/- 30 cm H2O/L H2O, and a decrease
      in pulmonary compliance from 0.4 +/- 0.05 to 0.12 +/- 0.06 mL/cm H2O.
      CONCLUSIONS: This in situ, syngeneic rat lung transplantation model offers an
      alternative to large animal models for verification of lung preservation
      solutions and for modification of donor or recipient treatment regimens.

PMID- 8561551
TI  - Esophagectomy for carcinoma in the octogenarian.
AB  - BACKGROUND: Esophageal carcinoma is predominantly a disease of the elderly, a
      group often only considered for palliative therapies. METHODS: A case note review
      identified 31 octogenarians undergoing resection for carcinoma of the esophagus
      or gastric cardia over a 12-year period ending December 1994. RESULTS: Nineteen
      patients made either an uncomplicated postoperative recovery (n = 12) or suffered
      minor complications (n = 7). Of the 12 patients who suffered moderate or severe
      complications, 5 died (in-hospital mortality, 16%). The deaths included 2 of 3
      patients who underwent emergency operation for esophageal perforation and 3 of 28
      patients who underwent elective esophagectomy (elective mortality rate, 10.7%).
      Nineteen of the 26 survivors (73%) experienced no further dysphagia. The 5-year
      survival rate was 17%. CONCLUSIONS: Elective esophageal resection can be
      performed safety in selected octogenarians who have no or few coexisting medical
      problems and present with a localized carcinoma that is technically easy to
      resect. Patients undergoing emergency operations or in whom moderate or severe
      postoperative complications develop often have poor physiologic reserve and are
      therefore at risk of early postoperative death.

PMID- 8561552
TI  - Closed drainage using Redon catheters for local treatment of poststernotomy
      mediastinitis.
AB  - BACKGROUND: Continuous irrigation has been used worldwide for the treatment of
      acute poststernotomy mediastinitis. However, its high rate of failure led to the
      development of new methods, among them closed drainage with Redon catheters.
      METHODS: We evaluated the results obtained with Redon catheters in 70 patients,
      and compared them to those obtained in 38 patients treated with continuous
      irrigation. RESULTS: The two treatment groups were not different for age, type of
      cardiac operation, and initial severity of illness. Local failure of Redon
      catheter drainage occurred less frequently (20 of 38 versus 9 of 70 patients; p =
      0.0001). This reduced failure rate was mainly attributable to a lower incidence
      of superinfections (10 of 38 versus 2 of 70 patients; p = 0.0002), but also to a
      lower incidence of primary failure (10 of 38 versus 7 of 70 patients; p = 0.026).
      Mortality was significantly decreased (15 of 38 versus 12 of 70 patients; p =
      0.01). The other major advantage of this technique was the simplicity of its use.
      CONCLUSIONS: The technique using Redon catheters should be considered an
      effective and convenient treatment of acute poststernotomy mediastinitis.

PMID- 8561553
TI  - Resection of pulmonary nodules using video-assisted thoracic surgery. The Thorax
      Group.
AB  - BACKGROUND: The aim of this study was to assess the experience with video
      assisted thoracic surgery for the resection of pulmonary nodules. METHODS: This
      voluntary registry (20 centers) included 388 patients with either benign (n =
      171) or malignant (n = 217) pulmonary nodules. Pulmonary nodules were located
      using computed tomography scan-guided injection of methylene blue (59 patients)
      and hook wire technique (17 patients). RESULTS: Video-assisted thoracic surgery
      was converted into thoracotomy in 67 patients (17%) because of technical
      emergency in 4, inability to complete resection in 33, and the need to perform
      lobectomy for cancer through thoracotomy in 30. In other patients, video-assisted
      thoracic surgery allowed wedge resection in 300 cases and lobectomy in 21 cases.
      No intraoperative and two postoperative deaths (0.56%) occurred. The complication
      rate was 8% (n = 31). Mean durations of chest tube placement and hospital stay
      were 3.3 days (range, 1 to 20 days) and 6 days (range, 1 to 25 days),
      respectively. Video-assisted thoracic surgery was judged by the surgeon to be a
      diagnostic procedure 226 times (58%) and a therapeutic procedure 162 times (42%).
      CONCLUSION: Video-assisted thoracic surgery appears to be safe and remains mainly
      a diagnostic procedure for malignant tumors.

PMID- 8561554
TI  - Protein-losing enteropathy after Fontan operation: resolution after baffle
      fenestration.
AB  - A 4-year-old child with hypoplastic left heart syndrome and a 6-year-old child
      with tricuspid atresia had both undergone staged reconstructive operations
      culminating in a Fontan operation. Peripheral edema, ascites, and hypoalbuminemia
      refractory to dietary manipulation and steroid therapy developed in both
      patients. After hemodynamic assessment, each child underwent surgical creation of
      a 4.8-mm fenestration in the previously placed baffle that separated the systemic
      venous pathway from the pulmonary venous atrium. Peripheral edema and ascites
      promptly resolved and serum protein levels normalized within 2 weeks after
      operation. Systemic arterial saturation is 86% in each child, and both children
      remain clinically well with no evidence of protein-losing enteropathy on normal
      diets and without specific medical therapy.

PMID- 8561555
TI  - Giant pericardial cysts.
AB  - Pericardial cysts are most commonly incidental radiologic findings of little
      clinical consequence. We present the unusual history of 2 patients in whom
      pericardial cysts were of massive sizes and caused significant symptoms; in 1,
      progression of the cyst size had been documented over 25 years. Diagnostic
      difficulties encountered and the utility of video-assisted thoracoscopy are
      described.

PMID- 8561556
TI  - Outcome as a function of annual coronary artery bypass graft volume. The Ad Hoc
      Committee on Cardiac Surgery Credentialing of The Society of Thoracic Surgeons.
AB  - BACKGROUND: Recent changes in health care financing have raised the specter of
      operation-specific, volume credentialing for cardiac surgeons. To meet this
      challenge, the leadership of The Society of Thoracic Surgeons formed an Ad Hoc
      Committee to study the question of the relationship of case volume to outcome.
      One product of the committee's work in this analysis of data from The Society of
      Thoracic Surgery National Cardiac Database. METHODS: We examined data for all
      types of coronary artery bypass graft-only operations (n = 124,793) from more
      than 1,200 surgeons working in more than 600 hospitals for the years 1991 through
      1993. All in-hospital and 30-day out-of-hospital mortality, both observed and
      expected as predicted by The Society of Thoracic Surgeons risk stratification
      method, was plotted against annualized group practice volume. Both patient-based
      and practice-based sampling techniques were used. RESULTS: The data show that
      observed mortality ranged from 2.0% to 3.6% for practices of more than 100 cases
      through practices with more than 900 cases per year. Those practices with less
      than 100 cases (n = 18) had a mean mortality of 5%. Expected mortalities ranged
      from 2.4% to 3.9% and did not vary as a function of volume. No practice volume
      category had an observed/expected ratio of less than 0.8 and none had a ratio
      greater than 1.2, if annual volume was more than 100. Practices of less than 100
      cases/year had an observed/expected ratio of 1.6% to 1.7%. There was great
      variation in observed and expected mortalities in the lower volume categories and
      less variation when volume was greater (more than 600 cases/year). CONCLUSIONS:
      Although the data are practice-group-specific only, there was no clinically
      relevant correlation of volume to outcome except at extremely low annual volume
      (less than 100 cases per year). Variability of outcome was significant in lower
      volume practices (less than 600 cases/year) and varied little at more than 600
      cases per year. There were no differences in expected mortality regardless of the
      size of the practice.

PMID- 8561557
TI  - Staged repair of tetralogy of Fallot and pulmonary atresia without central
      pulmonary arteries.
AB  - A 15-year-old boy with tetralogy of Fallot and pulmonary atresia without central
      pulmonary arteries who was successfully treated using a staged approach is
      presented. The first stage consisted of the creation of central pulmonary
      arteries. In the second stage, the continuity between the right ventricle and the
      pulmonary arteries was established with closure of the ventricular septal defect.
      Some patients previously considered to be unsuitable candidates for correction
      may be successfully repaired using this approach.

PMID- 8561558
TI  - Excision of a pulmonary valve abscess in a 61-year-old woman with single
      ventricle.
AB  - A 61-year-old woman with levo-transposition of the great arteries, double-inlet
      single left ventricle, and valvar and subvalvar pulmonary stenosis presented with
      a large pulmonary valve vegetation unresponsive to antibiotic therapy. The
      diagnostic evaluation and the surgical management are discussed. At operation the
      pulmonary valve was excised and an abscess cavity was obliterated with a
      pericardial patch. She is currently doing well 3 years after the operation.

PMID- 8561559
TI  - Primary sternal closure and mediastinal decompression by inlay autologous rib
      grafts.
AB  - Hemodynamic instability and arrhythmia after cardiopulmonary bypass occasionally
      requires delayed sternal closure or placement of a stenting device. A primary
      sternal closure with autologous inlay rib grafts can ensure a secure, stable
      sternal repair and avoids prolonged ventilator support and the concerns, risks,
      and expense associated with a secondary sternotomy repair.

PMID- 8561560
TI  - Multiple polyposis and adenocarcinoma arising in Barrett's esophagus.
AB  - Adenomatous polyps of the esophagus are rare in comparison with those of the
      lower gastrointestinal tract. Like adenomatous colon polyps, they have been
      associated with malignancy. We describe a case of early adenocarcinoma and
      multiple polyposis of the esophagus arising in a Barrett's epithelium, treated
      with surgical resection.

PMID- 8561561
TI  - Coronary artery endarterectomy for retrieval of entrapped percutaneous
      angioplasty catheter.
AB  - A 70-year-old patient underwent percutaneous transluminal coronary angioplasty of
      a calcified tight mid-right coronary artery lesion, when the balloon burst and
      could not be retrieved. Even on cardiopulmonary bypass, the catheter could not be
      extracted through a proximal aortotomy. The patient had a distal reversed
      saphenous vein graft inserted into the right coronary artery. The catheter was
      ultimately removed after an endarterectomy of the calcified lesion.

PMID- 8561562
TI  - First-rib exostosis bursa.
AB  - We describe a case of exostosis bursa of the first left rib. Clinical features,
      investigations, and surgical management are described in detail.

PMID- 8561563
TI  - Truncus arteriosus with total anomalous pulmonary venous return and interrupted
      arch.
AB  - An infant with truncus arteriosus, total anomalous pulmonary venous return of the
      supracardiac type and interrupted aortic arch distal to the left subclavian
      artery is presented. One-stage repair was performed in the newborn period using a
      12-mm aortic homograft. Recovery was complicated by congenital stenosis of the
      left main bronchus. The cardiovascular status remains stable 2 years after
      repair.

PMID- 8561564
TI  - Pheochromocytomas with extension into central vascular structures.
AB  - Two cases of pheochromocytomas, 1 with extension into the inferior vena cava and
      the second with involvement of the right atrium, are reported. Both tumors were
      resected in toto, 1 using inferior to superior vena cava vein-to-vein bypass and
      the second with the aid of hypothermic circulatory arrest. Both patients are free
      of recurrences or metastasis 20 and 24 month postoperatively.

PMID- 8561565
TI  - Heart transplantation with bicaval anastomoses after a maze operation.
AB  - A 49-year-old man had progressive low cardiac output syndrome after mitral valve
      repair combined with a maze operation. A biventricular assist device was
      implanted and, finally, emergency orthotopic heart transplantation was performed.
      The multiple incisions, especially right atrial incisions, were successfully
      avoided by heart transplantation with bicaval anastomoses.

PMID- 8561566
TI  - Primary sternal osteomyelitis.
AB  - A case report of primary sternal osteomyelitis, a rare clinical entity, is
      presented. Treatment of primary sternal osteomyelitis is antibiotics and complete
      debridement of the infected bone and anterior periosteum. If the posterior
      sternal periosteum is not involved, it should be left intact. The defect can be
      covered with skeletal muscle flaps, which improves healing and minimizes
      recurrence. This approach led to a complete and timely cure.

PMID- 8561567
TI  - Inhaled nitric oxide as an adjunct to pulmonary thromboendarterectomy.
AB  - In chronic pulmonary vascular thrombotic disease, pulmonary thromboendarterectomy
      has proved to be effective in reducing pulmonary hypertension and improving gas
      exchange. However, persistent pulmonary hypertension and unrelenting reperfusion
      edema are the main causes of death. We report a case of pulmonary
      thromboendarterectomy followed by an immediate unfavorable postoperative course
      with acute and persistent pulmonary hypertension, gas exchange impairment, and
      heart dysfunction. In this particular case, inhaled nitric oxide was successfully
      administered.

PMID- 8561568
TI  - Anomalous course of the left main coronary artery in tetralogy of Fallot.
AB  - An extremely rare coronary artery anomaly where the left main coronary artery
      arose anteriorly from the right coronary sinus and coursed in front of the right
      ventricular outflow tract was present in a patient with tetralogy of Fallot.
      Preoperative angiocardiography was interpreted as normal. Operative recognition
      was prevented by dense adhesions and a partial intramural course. Division of the
      vessel at repair resulted in death of the patient. The angiographic pattern
      associated with this anomaly is very unusual, and in many views looks deceptively
      normal. Details are presented.

PMID- 8561569
TI  - Late contralateral lobectomy after single-lung transplantation for emphysema.
AB  - Cases of hyperinflation of native emphysematous lung have been reported in the
      early period after single-lung transplantation. We report a case of a similar
      complication that occurred 2 years after transplantation and was successfully
      treated by lobectomy.

PMID- 8561570
TI  - Early pulmonary homograft failure from dilatation due to distal pulmonary artery
      stenosis.
AB  - Early progressive pulmonary homograft insufficiency developed in an 11-month-old
      infant after repair of truncus arteriosus because of dilatation secondary to the
      presence of residual distal pulmonary artery stenosis and hypoplasia. Before
      repair, the pulmonary artery branches were discontinuous, with the right
      pulmonary artery being somewhat hypoplastic and originating from the trunk, and
      the left pulmonary artery supplied by a modified Blalock-Taussig shunt created in
      the newborn period. At repair, a pulmonary homograft was used to connect the
      branches. Progressive cardiomegaly and oxygen dependance occurred 3 weeks
      postoperatively. Cardiac catheterization showed systemic right ventricular
      pressure, severe homograft insufficiency, and residual distal pulmonary artery
      stenosis and hypoplasia. On reoperation at 3 months postoperatively, the
      homograft annulus diameter increased from 14 mm to 16 mm. Dilatation and
      insufficiency probably occurred because the right ventricle and homograft distal
      to the obstruction functioned as a unit during systole. The problem might have
      been minimized with the use of aortic homograft, which is thicker, or annular
      reinforcement with a synthetic material.

PMID- 8561571
TI  - Subclavian vein cannulation: an approach with definite landmarks.
AB  - An interesting observation, ie, the coracoclavicular line (from the lower border
      of the coracoid process to the upper border of the medial head of the clavicle)
      was parallel to the subclavian vein catheter in bedside chest roentgenograms
      (anteroposterior view), prompted us to use this subclavian approach. After supine
      positioning of the patient with the arm alongside the body and the left shoulder
      elevated 10 to 15 degrees, the puncture point was selected 1.5 cm away from the
      point where the coracoclavicular line crossed inferior border of the clavicle on
      the skin. The needle was moved horizontally in the direction of the aforesaid
      line. In 205 attempts in adult patients, 95.6% patients had successful
      cannulation in first attempt without significant complication. This technique
      appears to be promising as it is based on observation and is guided by constant
      landmarks and precise direction.

PMID- 8561572
TI  - Technique for extraanatomic bypass in complex aortic coarctation.
AB  - A variety of approaches and surgical techniques have been described for the
      management of recurrent coarctation. When there is an additional intracardiac
      defect that requires surgical correction it is preferable to correct both lesions
      simultaneously and through the same incision. This article reports two new
      techniques of connecting ascending to descending aorta using an intrathoracic
      conduit and performed through a median sternotomy.

PMID- 8561573
TI  - Reversed bevel technique for anastomosis at the aortic arch.
AB  - We describe a method for performing the distal anastomosis in replacement of the
      ascending and the proximal arch of the aorta with specific attention to obtaining
      accurate length and orientation of the graft. This method reduces the incidence
      of both anastomotic dehiscence due to tension and obstruction caused by redundant
      graft.

PMID- 8561574
TI  - Modified method for Novacor left ventricular assist device implantation.
AB  - We have developed and applied in 7 cases an alternative "orthodromic" technique
      for Novacor left ventricular assist device implantation. After sternotomy, the
      pocket is tailored, dividing the insertion of the diaphragm to the lower ribs,
      for easier bleeding control. On cardiopulmonary bypass, the aorta is cross
      clamped and cardioplegia administered. Apical cannulation is performed first on a
      dry, still field. The device is then easily deaired, with blood flowing in the
      physiologic direction. The aorta is declamped and the outflow conduit is
      anastomosed. Before the suture is tied, the final deairing is obtained. This
      technique allows extreme precision in apical cannulation, easier control of
      bleeding, and accurate deairing of the pump. The ischemic time is short and
      damage to the right ventricle negligible.

PMID- 8561575
TI  - F. John Lewis, MD: 1916-1993.
AB  - F. John Lewis performed the first successful open heart operation in 1952. He was
      the first full-time member of the faculty of surgery at Northwestern University.
      This article gives a brief biography of this great surgeon.

PMID- 8561576
TI  - The dendritic cell lineage: a ubiquitous antigen-presenting organization.
AB  - Dendritic cells are specialized antigen-presenting cells with two unique
      characteristics: the greatest stimulatory potential and the ability to stimulate
      naive T-lymphocytes. They originate from the bone marrow and reach their
      destination via hematogenous or lymphatic migration. Their phenotype is
      characterized by a high expression of major histocompatibility complex class II
      molecules and a high expression of adhesion molecules (CD25, CD54, CD58, CD72,
      and CD80). Pulmonary dendritic cells may be investigated by histologic
      examination, phenotype analysis, and function studies in a mixed lymphocyte
      reaction. Their isolation requires enzymatic digestion of lung tissue and
      subsequent steps of cell separation. The complexity of these manipulations makes
      it difficult to obtain large numbers of viable cells. A close anatomic
      relationship with alveolar macrophages underlines a functional interconnection:
      macrophages down-regulate the antigen-presenting function through release of
      tumor necrosis factor alpha. Dendritic cells most probably play a major role in
      lung diseases such as histiocytosis, primary and secondary cancers, and both
      acute and chronic lung graft rejection. Identification of the precise functional
      pathways might lead to therapeutic use of modulation of dendritic cell function.

PMID- 8561577
TI  - Cardiopulmonary bypass in pregnancy.
AB  - The cardiopathic patient can sustain acute heart failure during pregnancy. In
      such cases, if open heart operation is necessary to save the patient's life, the
      fetus could be seriously compromised after exposure to cardiopulmonary bypass.
      From 1958 to 1992, 69 reports of cardiac operations during pregnancy with the aid
      of cardiopulmonary bypass have been published. Maternal mortality was 2.9%.
      Embryofetal mortality was 20.2%. Examining only the last 40 patients, maternal
      and embryofetal mortality were 0.0% and 12.5%, respectively. Embryofetal
      mortality was 24.0% when hypothermia was used, compared with 0.0% while operating
      in normothermia. Maternal mortality did not change. The use of hypothermia during
      cardiopulmonary bypass provoked uterine contractions in several patients.
      Hypothermia decreases O2 exchange through the placenta. Pump flow and mean
      arterial pressure during cardiopulmonary bypass seem to be the most important
      parameters that influence fetal oxygenation. We speculate that cardiac operation
      is not a contraindication to pregnancy prolongation.

PMID- 8561578
TI  - Thoracoabdominal aortic aneurysms.

PMID- 8561579
TI  - A model for predicting transfusion after coronary artery bypass grafting.
AB  - BACKGROUND: Blood conservation has become an important issue in cardiac surgery.
      This study was undertaken to determine if the need of blood transfusion could be
      predicted from preoperative patient variables. METHODS: From January 1, 1992, to
      December 31, 1993, 2,033 patients having isolated coronary artery bypass grafting
      procedures were studied; 1,446 (71%) were male and 587 (29%), female. The mean
      age was 65.1 +/- 9.9 years (range, 31 to 88 years). Emergency operation, urgent
      operation, and reoperations were done in 78 (4%), 188 (9%), and 189 (9%)
      patients, respectively. In the entire group, 1,245 (61%) received transfusion
      during hospitalization, and 788 (39%) did not. Logistic regression analysis was
      used to construct a model that predicted the need of transfusion of packed red
      blood cells after coronary artery bypass grafting. A transfusion risk score was
      constructed by assigning points to independent predictive factors on the basis of
      the logistic regression coefficient and the odds ratio. Preoperative predictors
      of transfusion were emergency operation, urgent operation, cardiogenic shock,
      catheterization-induced coronary occlusion, low body mass index, left ventricular
      ejection fraction lower than 0.30, age greater than 74 years, female sex, low red
      cell mass, peripheral vascular disease, insulin-dependent diabetes, creatinine
      level greater than 1.8 mg/dL, albumin value lower than 4 g/dL, and redo
      operation. RESULTS: The mean transfusion risk score for patients receiving 0, 1
      to 4, and greater than 4 units of packed red blood cells was 2.3 +/- 0.9, 5.2 +/-
      3.0, and 9.6 +/- 3.5, respectively (p = 0.001). Patients with a score higher than
      6 had a 95% transfusion incidence. The predictive model was validated on 422
      patients having coronary artery bypass grafting from January 1 to May 31, 1994.
      The observed rates of the validation group fell within the 95% confidence
      intervals of the predicted rates. CONCLUSIONS: These data demonstrate that
      readily available patient variables can predict patients at risk for transfusion.
      Routine use of aprotinin and other adjustments of cardiopulmonary bypass should
      be considered to reduce transfusion in high-risk patients.

PMID- 8561580
TI  - As originally published in 1988: The use of autologous pericardium for
      ventricular aneurysm closure. Updated in 1996.

PMID- 8561581
TI  - As originally published in 1988: Results of surgical treatment of patients with
      T3 non-small cell lung cancer. Updated in 1996.

PMID- 8561582
TI  - Conversion of postischemic ventricular fibrillation with intraaortic infusion of
      potassium chloride.

PMID- 8561583
TI  - Potassium conversion of ventricular fibrillation.

PMID- 8561584
TI  - Mediastinoscopy and superior vena caval obstruction.

PMID- 8561585
TI  - Warm heart surgery and stroke.

PMID- 8561586
TI  - Delayed chylothorax after irradiation.

PMID- 8561587
TI  - Cardiac troponin I release in heart transplantation.

PMID- 8561588
TI  - The surgical challenge of primary pulmonary artery sarcoma.

PMID- 8561589
TI  - Quality of retransfused blood: whole blood versus cell separation.

PMID- 8561590
TI  - Pneumonectomy for chronic infection: fraught with danger?

PMID- 8561591
TI  - Experience with generally accepted centrifugal pumps: personal and collective
      experience.
AB  - BACKGROUND: The data presented are a brief summary of The International Registry
      for Mechanical Ventricular Assist Pumps and Artificial Hearts and a summary of
      the personal experience of the Minnesota Thoracic Associates at the Minneapolis
      Heart Institute with the use of the Sams centrifugal pump from May 1985 to
      September 1994. METHODS: Ventricular support with the use of centrifugal pumps
      for postcardiotomy shock consisted of cannulation of the left atrium and aorta
      for left ventricular support and the right atrium and pulmonary artery for right
      ventricular support, or the combination of the two for biventricular support.
      RESULTS: The average survival and discharge rate recorded by the National
      Registry for postcardiotomy syndrome was 25.3%. Our experience at Minnesota
      Thoracic Associates was 54%. The National Registry reported 45.7% of the patients
      being weaned from the device or receiving transplants and 25.3% of the patients
      ultimately discharged from the hospital. Sixty-five percent of the patients in
      our experience either were weaned from the device or received a transplant for an
      overall discharge rate of 42%. The average effective hospital cost per survivor
      was almost $400,000.00. CONCLUSIONS: It is our belief that when considering the
      cost analysis of temporary devices, one must conclude that a more economical
      approach for the treatment of end-stage cardiac disease would be aggressive
      development of a permanent ventricular assist device.

PMID- 8561592
TI  - Bio-Medicus centrifugal ventricular support for postcardiotomy cardiac failure: a
      review of 129 cases.
AB  - BACKGROUND: Bio-Medicus centrifugal ventricular support has been used widely for
      postcardiotomy cardiac failure. The purpose of this study was to review a large
      series of support patients examining complications and outcomes. METHODS: One
      hundred twenty-nine patients undergoing cardiac operations at The Methodist
      Hospital in Houston, Texas, were placed on Bio-Medicus centrifugal ventricular
      support for postcardiotomy cardiac failure; 102 were male and 27 were female with
      a mean age of 61.6 years. These patients were selected for ventricular support
      based solely on failure to be weaned from cardiopulmonary bypass or progressive
      postcardiotomy cardiac failure shortly after arrival in the intensive care unit.
      RESULTS: These patients experienced numerous complications including
      coagulopathy, renal insufficiency or failure, sepsis, neurologic deficits,
      ventricular failure, arrhythmias, and death; 56.3% of patients were weaned from
      mechanical support and 21.0% were discharged alive. Causes of death included
      ventricular failure (62.4%), arrhythmias (12.9%), triage (6.9%), perioperative
      myocardial infarction or cardiac arrest (5.0%), coagulopathy (4.0%), sepsis
      syndrome (4.0%), cardiac graft failure (3.0%), and device related (1.0%). The one
      device-related death was a venous cannula dislodgment in the intensive care unit
      with subsequent exsanguination. Device-related complications were seen in only
      1.6% of patients. CONCLUSIONS: Bio-Medicus centrifugal ventricular support can be
      implemented rapidly and relatively easily. There are few device-related
      complications and the cost is relatively inexpensive compared with other assist
      systems. This series demonstrates that a substantial number of patients who
      experience reversible postcardiotomy myocardial injury will benefit from
      temporary centrifugal ventricular support.

PMID- 8561593
TI  - Use of centrifugal pumps for postcardiotomy ventricular failure: technique and
      anticoagulation.
AB  - BACKGROUND: Centrifugal pumps have been employed most commonly for postcardiotomy
      mechanical support after intraaortic balloon pumping has failed. Despite their
      effectiveness in some patients, morbidity remains high. METHODS: Our clinical
      experiences with centrifugal pumps were reviewed with particular attention to
      common morbidity such as bleeding, coagulopathy, and thromboembolism. Evolution
      of cannulation techniques and anticoagulation strategies were defined. Morbidity
      during early and more recent experience was compared. RESULTS: Deranged
      coagulation and excessive mediastinal bleeding were commonly observed in patients
      undergoing centrifugal mechanical assist for postcardiotomy cardiogenic shock.
      Evolved strategies to reduce blood loss included meticulous cannulation
      techniques, early use of blood components, and an aggressive policy of
      mediastinal reexploration. Thromboembolism occurred with centrifugal mechanical
      assist, was underestimated by clinical events, and dictated pursuit of improved
      anticoagulation strategies and device refinement. A clinically significant trend
      of decreasing morbidity from early to recent experience was observed.
      CONCLUSIONS: Increasing clinical experience with centrifugal mechanical assist
      appears to result in a clinically relevant decrease in morbidity.

PMID- 8561594
TI  - ABIOMED BVS 5000: experience and potential advantages.
AB  - BACKGROUND: The ABIOMED BVS 5000 is a two-chambered extracorporeal pulsatile
      assist device intended for temporary circulatory support. The Food and Drug
      Administration granted approval for the device for postcardiotomy patients in
      1992. METHODS: A worldwide registry is maintained with the BVS 5000. Currently
      500 patients have been entered into the registry. The majority of patients were
      postcardiotomy (53%) and required biventricular assist devices (65%). RESULTS:
      Postcardiotomy patients have had a 27% discharge rate compared with
      cardiomyopathy patients with a more than 40% discharge rate. Comparison at Baylor
      University Medical Center of the ABIOMED BVS 5000 with a nonpulsatile device
      demonstrated an improved wean rate (60% versus 47%, respectively) as well as
      discharge rate (27% versus 17%, respectively). CONCLUSIONS: A worldwide registry
      combined with the experience at Baylor University Medical Center demonstrates the
      capability of the BVS 5000 to support postcardiotomy patients. The device is
      safe, simple, and effective. In addition, the pulsatile nature of the circulatory
      support appears to offer advantages over other systems.

PMID- 8561595
TI  - Experience with right ventricular assist devices for perioperative right-sided
      circulatory failure.
AB  - BACKGROUND: Right-sided circulatory failure remains a significant source of
      morbidity and mortality for both cardiac transplant and left ventricular assist
      device recipients. METHODS: We reviewed our experience with 11 patients who
      required a right ventricular assist device (RVAD) after either orthotopic heart
      transplantation or left ventricular assist device implantation. Variables
      analyzed included total time of RVAD support, hemodynamic and hematologic
      parameters, and parameters of end-organ perfusion. These were assessed at five
      time points: (1) at least 2 weeks before RVAD implantation, (2) intraoperatively
      just before RVAD insertion, (3) while on RVAD support, and, for those who
      survived, (4) just before RVAD explantation, and (5) off RVAD support. Survival
      was assessed as the ability to be weaned successfully from RVAD support. Urine
      output and serum transaminase levels were recorded throughout the period of RVAD
      support. RESULTS: Five patients received an ABIOMED 5000 BVS RVAD, and 6 received
      a Bio-Medicus centrifugal pump. Nine patients in the study underwent orthotopic
      heart transplantation and had development of right-sided circulatory failure from
      0 to 96 hours after donor organ insertion, and 2 patients underwent left
      ventricular assist device implantation 12 to 48 hours before RVAD support. The
      mean time of RVAD support for survivors was 133.6 +/- 33.6 hours (range, 107 to
      190 hours). Six patients were successfully separated from RVAD support, and 5
      patients died while on RVAD support. Causes of death included sepsis (2),
      biventricular failure (2), and coagulopathy (1). Continuous arteriovenous
      hemodialysis was employed in 3 of 6 survivors and 1 of 5 nonsurvivors.
      CONCLUSIONS: Right ventricular assist devices work most effectively if implanted
      early enough to avoid significant, potentially irreversible end-organ injury. We
      liberally employ continuous arteriovenous hemodialysis, minimize the use of
      heparin immediately postoperatively, keep patients sedated, and continue RVAD
      support until the patient displays signs of hemodynamic and end-organ recovery as
      heralded by (1) a decrease in central venous pressure and, more importantly, a
      decrease in pulmonary artery diastolic pressure, (2) an increase in urine output,
      and (3) a decrease in serum transaminase levels.

PMID- 8561596
TI  - Mechanical circulatory support with the Thoratec assist device in patients with
      postcardiotomy cardiogenic shock.
AB  - BACKGROUND: In spite of modern cardiac surgical techniques, severe cardiogenic
      shock not responding to pharmacologic therapy and intraaortic balloon pumping
      develops in about 0.2% to 1.2% of patients undergoing cardiac operations.
      METHODS: From September 1987 to September 1994, 184 patients were supported with
      different mechanical circulatory support systems. Nine patients with
      postcardiotomy cardiogenic shock were supported with the Thoratec ventricular
      assist device. Four patients suffered early postcardiotomy cardiogenic shock, and
      5 patients suffered late postcardiotomy cardiogenic shock. In 6 patients the
      Thoratec device was applied exclusively, in 2 patients both Bio-Medicus and
      Thoratec, and in 1 patient both ABIOMED and Thoratec devices were used. Duration
      of support ranged from 5 to 46 days with a mean duration of 15 days. RESULTS:
      Four patients (44%) survived and were discharged. Main complications and causes
      of death were multiple organ failure and sepsis. CONCLUSIONS: The results justify
      the use of Thoratec assist device in patients with severe preoperative
      cardiogenic shock.

PMID- 8561597
TI  - Ventricular assist systems: experience in Japan with Toyobo pump and Zeon pump.
AB  - BACKGROUND: Two types of ventricular assist systems have been approved for use by
      the Japanese government. METHODS: The two government-approved ventricular assist
      systems, the Toyobo pump (National Cardiovascular Center type) and the Zeon pump
      (Tokyo University type), were applied to 219 patients in Japan as of October 20,
      1994. RESULTS: Adult-sized were used in 211 patients and pediatric ones in 8
      patients. Left ventricular assist systems was performed in most cases (82.6%).
      The predominant indication was failure to be weaned from cardiopulmonary bypass
      (65.8%). The duration of ventricular assist system application ranged from 1 hour
      to 70 days, and the mean was 7.3 days, excluding the patients with
      cardiomyopathy. The weaning rate was 48.8% and the survival rate was 25.6%. Main
      causes of death were heart failure including unrecoverable heart failure and
      multiple organ failure. In 12 cardiomyopathy patients, Toyobo pumps were applied
      as left ventricular assist systems. Support duration was from 13 days to 192 days
      (ongoing). One patient was bridged to transplantation successfully and 1 was
      weaned after 3 months of support. CONCLUSIONS: From these data, the Toyobo pump
      and the Zeon pump are useful for short-term support for acute, profound heart
      failure. The Toyobo pump also may provide sufficient support as a bridge to
      transplantation for the medium term.

PMID- 8561598
TI  - Hemopump 31, the sternotomy Hemopump: clinical experience.
AB  - BACKGROUND: Postcardiotomy cardiogenic shock remains a challenging situation.
      Many devices can be used although none of them directly unload the left ventricle
      except for the Hemopump. We report our clinical experience with the Hemopump 31
      or sternotomy Hemopump. METHODS: From 1992 to 1994, 15 patients received a
      Hemopump 31. All suffered postcardiotomy cardiogenic shock either after coronary
      artery bypass grafting (n = 14) or after heart transplantation (n = 1). Patients
      enrolled had refractory heart failure despite the use of optimal inotropic
      support. Three groups can be identified: group 1 (n = 2 patients), double
      Hemopump right and left; group 2 (n = 4), patients with delayed insertion after
      intraaortic balloon pump failure; and group 3 (n = 9 patients), immediate
      insertion. The average support of duration for the survivors was 5 days. RESULTS:
      No mechanical failure or device-related complication was noticed. There were
      striking differences between groups 1 and 2 as opposed to group 3, as only 1
      patient survived in group 2 and none in group 1, as opposed to 5 patients in
      group 3. Overall survival is 40%. All patients were discharged from the hospital.
      CONCLUSIONS: Factors showing adverse effect are biventricular failure,
      vasoconstrictor requirement, and delayed insertion. We believe the Hemopump is a
      more efficient device than the intraaortic balloon pump, and that early use after
      onset of heart failure achieves better results.

PMID- 8561599
TI  - Uniformity of perfusion in all regions of the human heart by warm continuous
      retrograde cardioplegia.
AB  - BACKGROUND: Animal models have suggested that retrograde cardioplegia may be
      poorly distributed to septal and right ventricular regions of the heart; if true,
      this may have dangerous implications for warm continuous retrograde cardioplegia
      in humans. We have previously shown that blood gases from coronary arteries
      during warm continuous retrograde cardioplegia represent postcapillary "venous"
      gases and are reflective of myocardial perfusion. METHODS: To determine regional
      differences in perfusion during warm continuous retrograde cardioplegia we
      obtained blood gases from three regions of the heart in 141 consecutive patients
      undergoing coronary artery bypass grafting, aortic valve replacement, or both.
      Right heart perfusion was determined by blood gases from the right coronary
      artery orifice, acute marginal, or posterior descending coronary arteries;
      circumflex or lateral wall perfusion was determined by samples from obtuse
      marginal or intermediate coronary arteries; and anterior wall/septal perfusion
      was determined by left anterior descending and diagonal coronary artery blood
      gases. Warm continuous retrograde cardioplegia flow ranged from 150 to 300 mL/min
      depending on heart size. A mean of 4 +/- 1 samples/patient were obtained.
      RESULTS: There were no regional differences in postcapillary pH, carbon dioxide
      tension, or CO2 production during warm continuous retrograde cardioplegia. Oxygen
      tensions were lower in the right and anterior/septal regions of the heart,
      implying more O2 uptake. No regional acidosis, consistent with poor perfusion,
      could be detected. CONCLUSIONS: We conclude that, unlike experimental models,
      regional myocardial perfusion, including the right heart, is uniform during "high
      flow" warm continuous retrograde cardioplegia in humans.

PMID- 8561600
TI  - Heparin-bonded surfaces in extracorporeal membrane oxygenation for cardiac
      support.
AB  - Development of increasingly complex perfusion devices with bonded heparin allowed
      for significant improvement of thromboresistance of most basic components
      required for cardiopulmonary bypass. In his recent review of heparin-coated
      cardiopulmonary bypass circuits, Gravlee cited 91 references dealing with heparin
      coated surfaces, and far more can be found if the search includes material
      technology or heparin-coated devices not designed for cardiopulmonary bypass (eg,
      ventricular assist devices, hemofilters, catheters). The present review is
      focused on long-term application of heparin-coated equipment in conjunction with
      basic work on heparin bonding relevant for extracorporeal membrane oxygenation.
      Experimental open chest cardiopulmonary bypass using heparin-coated equipment
      without systemic heparinization up to 36 hours has shown improved
      thromboresistance, and better platelet preservation was demonstrated for
      perfusion with heparin-coated cardiopulmonary bypass equipment up to 5 days in
      the experimental set-up. Similar findings were reported for roller pump perfusion
      with heparin-coated tubing and centrifugal pump perfusion with heparin-coated
      pump heads. More recently, heparin bonding was also made available for
      oxygenators with true membranes that preclude plasma leakage. The available
      knowledge on clinical applications of heparin-coated perfusion equipment is
      mainly based on short-term applications like ours, which now includes more than
      300 patients. Reduced postoperative blood loss and as a result fewer transfusions
      were the main benefits of heparin-coated equipment allowing for perfusion with
      low systemic heparinization. There are only a few reports on long-term use of
      heparin-coated equipment for prolonged circulatory support. However, the longest
      clinical application of a single device is that of an intravascular gas exchanger
      that remained fully functional during a 29-day implantation period. Finally, it
      appears, that circulating protamine interacts with surface-bound heparin.
      Protamine administration should therefore be avoided during perfusion with
      heparin-bonded equipment to maintain the improved thromboresistance.

PMID- 8561601
TI  - Extracorporeal membrane oxygenation for cardiac support in children.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) support for cardiac
      failure has been used in children since 1981 at the Children's Hospital in
      Pittsburgh. Most children required support after cardiac operations. Recently,
      however, a larger number of patients with decompensated cardiomyopathy or
      myocarditis have been supported with ECMO, which was used as a bridge to
      transplantation in most. METHODS: From 1981 to 1994, 68 children were placed on
      ECMO for cardiac support. RESULTS: The overall survival for the entire time
      period was 38%, with the more recent experience survival increased to 47%. In 14
      children, ECMO was used as a bridge to transplantation, with 9 children receiving
      a heart transplant and 7 long-term survivors. Extracorporeal membrane oxygenation
      has also been used to resuscitate 11 children after sudden cardiac arrest, with a
      long-term survival of 53%. CONCLUSIONS: We conclude that ECMO support for severe
      cardiac failure is effective. Patient selection and the use of heart
      transplantation for intractable heart failure have improved the overall survival.

PMID- 8561602
TI  - Total artificial heart: from bridge to transplantation to permanent use.
AB  - BACKGROUND: Pneumatic artificial hearts have played an important role in
      supporting the circulation in patients before cardiac transplantation. Pneumatic
      hearts have also been used for permanent cardiac replacement, but most agree they
      have serious limitations. METHODS: Several groups are now developing electric
      artificial hearts in which electrical energy crosses the skin using a wireless
      technique. The electrical energy powers a small direct-current motor, which
      actuates the blood pump. RESULTS: Important progress in these devices has
      resulted in animal survival with electric hearts of more than 1 year.
      CONCLUSIONS: Extensive bench testing and animal testing will be performed before
      the initial clinical use of these devices will be initiated. One of the early
      scientific achievements of the 21st century will be the initial use of the
      electric artificial heart in humans.

PMID- 8561603
TI  - Physiology of univentricular versus biventricular support.
AB  - Right ventricular failure unresponsive to pharmacologic treatment occurs in
      approximately 20% to 30% of patients supported with a left ventricular assist
      device (LVAD). The effect of the assistance on right ventricular function is
      highly controversial. Increased venous return produced by an LVAD can affect
      right ventricular function by increasing preload. On the other hand, an LVAD can
      improve the filling of the right ventricle by unloading the left ventricle,
      reducing its chamber size and shifting the septum back to the left. Right
      ventricular function is highly afterload dependent, the ventricular function
      depending on the pulmonary vascular resistance. With a normal pulmonary vascular
      bed, the LVAD can improve right ventricular function by reducing right
      ventricular afterload. If there is a fixed high pulmonary pressure, however, the
      LVAD can increase right ventricular afterload and volume. We conclude that the
      right ventricle is dispensable if the pulmonary vascular bed is normal.

PMID- 8561604
TI  - Left ventricular contributions to right ventricular systolic function during LVAD
      support.
AB  - BACKGROUND: In patients with postcardiotomy low cardiac output syndromes, right
      ventricular (RV) failure develops in approximately 25% of patients receiving left
      ventricular (LV) assist device support. Depressed RV function have been
      attributed to abnormalities of the RV myocardium, excessive load imposed on the
      RV during systole or diastole, or obstruction to RV inflow. However, recent
      studies also suggest that LV function may significantly affect RV function
      through ventricular interdependence. METHODS: We reviewed the data showing the
      importance of systolic ventricular interaction. We then related these
      observations to the RV response during LV assist device support, and present our
      ideas regarding the mechanisms responsible for this RV failure. RESULTS: Using an
      electrically isolated right heart preparation, Damiano observed double-peaked
      waveforms for RV pressure, and pulmonary artery blood flow occurred over a wide
      range (0 to 300 ms) of pacing intervals between the LV and RV. Numeric analysis
      indicated that RV systolic pressure and pulmonary artery blood flow were composed
      of both RV and LV components, with the LV component dominating (63.5% versus
      36.5%). CONCLUSIONS: The experimental studies indicate a very consistent RV
      response during LV assist device support: a decrease in RV afterload, increased
      compliance, and decreased contractility. In normal hearts, the net effect is an
      increase or no change in cardiac output. With a preexisting pathologic condition,
      the RV responses is qualitatively the same, but anatomic ventricular interaction
      is accentuated, leading to a greater decrease in RV contractility. The net effect
      is a decrease in cardiac output, which may require inotropic or RV mechanical
      support.

PMID- 8561605
TI  - Implantable LVAD infections: implications for permanent use of the device.
AB  - BACKGROUND: Infection in implantable left ventricular assist device (LVAD)
      patients is common and has serious implications regarding permanent use of the
      LVAD. METHODS: Thirty-three patients had HeartMate LVAD insertion as a bridge to
      heart transplantation. The mean length of hospital stay was 8 days before LVAD
      insertion. Before insertion 6 patients (18%) had positive pulmonary cultures and
      5 patients (15%) had bacteremia. RESULTS: During LVAD support 18 patients (55%)
      had bloodstream infection. Of 24 patients (73%) successfully bridged to
      transplantation, 12 (50%) had positive blood cultures including Staphylococcus
      species (n = 9), Candida (n = 3), Pseudomonas (n = 2), and Enterococcus (n = 2).
      Infectious complications encountered in this series included driveline infection
      requiring surgical revision, septic embolus, "cleared" device infection,
      "suppressed" device infection, and LVAD infection treated by device removal in 1
      patient and device exchange in another. CONCLUSIONS: Infection in implantable
      LVAD patients is common, especially in patients in whom multiple organ failure
      develops, requiring prolonged stay in the intensive care unit. Strategies are
      needed to prevent these infections in recipients of the permanent LVADs because
      treatment of an established infection is difficult and expensive.

PMID- 8561607
TI  - Infections during extended circulatory support: University of Alabama at
      Birmingham experience 1989 to 1994.
AB  - BACKGROUND: The University of Alabama at Birmingham experience with
      investigational ventricular assist devices (VADs) used as a bridge to
      transplantation has increased over the past several years; it now includes 27 VAD
      implantations with 13 VAD runs lasting for extended periods (ie, > 30 days). A
      review of complications experienced by patients during extended VAD runs is
      warranted before the further development and testing of chronically implanted
      mechanical circulatory support devices. METHODS: This study focuses on the
      infectious complications of extended VAD support; it includes 13 patients who
      were supported by either a Thoratec or HeartMate VAD for longer than 30 days
      pending cardiac transplantation. Infection was defined as any positive culture.
      The infections were classed according to site and severity as follows: class I
      were patient-related non-blood-borne infections, class II were blood-borne
      infections, class III were VAD percutaneous site infections, and class IV were
      infections of the blood-contacting surfaces or intracorporeal components of the
      VAD. RESULTS: The 8 Thoratec and 5 HeartMate patients were supported for a total
      of 1,648 days with a range of 33 to 279 days per patient. Every patient had at
      least one infection; however, there were 6 patients who had no class II or IV
      infections during the period of support. One of these 6 patients died of a
      stroke, whereas the other 5 patients survived VAD support. No trends were
      identified for a change in the incidence of bacterial compared with fungal
      infections during the course of VAD support. There was no trend for a greater
      number of infections in patients who died during VAD support compared with those
      who survived. Neither class II nor IV infections precluded transplantation. Three
      patients died during VAD support; 1 died as a direct consequence of fungal
      infection. Eight patients received transplants. One patient had an unanticipated
      recovery of cardiac function and the VAD was removed. Support in 1 patient is
      ongoing. CONCLUSIONS: Infection during VAD support pending cardiac
      transplantation is an important cause of morbidity and mortality in patients
      maintained for longer than 30 days by circulatory assist. Infectious
      complications will probably be a prominent component of the risk associated with
      the use of chronically implanted mechanical circulatory assist devices and will
      likely have an important effect on the quality of life experienced by these
      patients.

PMID- 8561606
TI  - Effects of endothelin-1 and L-arginine after cold ischemia in lamb hearts.
AB  - BACKGROUND: Prior studies from our laboratory have suggested an important role
      for the coronary endothelium in the injury resulting from hypothermic ischemia
      and reperfusion. A decreased endothelial response to intraarterial acetylcholine
      occurs after ischemia/reperfusion, implying a reduced release of the vasodilator
      nitric oxide by endothelial cells, but the role of endothelial-derived
      vasoconstrictor endothelin-1 in ischemia/reperfusion and interactions between
      endothelin-1 and nitric oxide in ischemia/reperfusion are still unclear. METHODS:
      We examined the effects of endothelin-1 and L-arginine, the precursor for nitric
      oxide, on functional recovery of isolated, blood-perfused neonatal lamb hearts
      undergoing 2 hours of ischemia at 10 degrees C. One group (n = 8) received 10
      pmol/L endothelin-1 before reperfusion, and a second group (n = 8) received a
      continuous infusion of 3 mmol/L L-arginine during the initial 20 minutes of
      reperfusion. The third group (n = 8) received both endothelin-1 and L-arginine in
      the same way as in the endothelin-1 and L-arginine groups. The fourth group
      underwent the same period of hypothermic ischemia without interventions during
      reperfusion. RESULTS: After 30 minutes of reperfusion, the endothelin-1-treated
      hearts showed significantly reduced recovery of left ventricular systolic
      function (positive maximum dP/dt and volume normalized [V10] dP/dt) and diastolic
      function (negative maximum dP/dt), coronary blood flow, and myocardial oxygen
      consumption compared with the control group (p < 0.05). These effects of
      endothelin-1 were offset to equal the values observed in controls having
      unmodified reperfusion by adding L-arginine. The L-arginine group had
      significantly greater recovery of left ventricular systolic function (positive
      maximum dP/dt, maximum developed pressure, dP/dt at V10, and developed pressure
      at V10) and diastolic function (negative maximum dP/dt), coronary blood flow, and
      myocardial oxygen consumption compared with the control group (p < 0.05).
      CONCLUSION: These results, combined with our previous observations that
      endothelin-1 levels are unchanged by hypothermic ischemia and reperfusion,
      suggest that there is an imbalance between the endothelial production of
      endothelin-1 and nitric oxide, which affects postischemic coronary blood flow and
      the recovery of ventricular function. Interventions that modify this imbalance of
      endothelially derived substances could favorably influence the outcome after a
      period of hypothermic ischemia and reperfusion.

PMID- 8561608
TI  - Insights into thromboembolism and bleeding.

PMID- 8561609
TI  - Thromboembolism and bleeding: clinical strategies.

PMID- 8561610
TI  - Patient selection for mechanical bridging to transplantation.
AB  - BACKGROUND: Patients with advanced heart failure often cannot undergo cardiac
      transplantation soon enough to prevent fatal hemodynamic deterioration or sudden
      death. The approach to these patients includes tailoring of medical therapy with
      vasodilators and diuretics, which allows stabilization of 60% to 80% of potential
      candidates. Current criteria for mechanical support before transplantation
      currently focus on the identification of hospitalized patients with at least 30%
      chance of death before transplantation. The much larger question relates to the
      potential use of mechanical support to bridge ambulatory patients, who represent
      90% to 95% of the transplant waiting list, with waiting times frequently
      exceeding 2 years. METHODS: From 1988 to 1993, 265 potential candidates were
      discharged after evaluation for transplantation with New York Heart Association
      class IV status and left ventricular ejection fraction of 0.25 or less. Patients
      were analyzed for clinical hemodynamic and echocardiographic profiles that would
      identify ambulatory patients unlikely to survive without urgent transplantation.
      RESULTS: After tailored medical therapy, presenting hemodynamic parameters are
      not useful for predicting 2-year survival without urgent transplantation, which
      was 45% at 2 years. Left ventricular diastolic dimension of 80 mm or greater was
      associated with only 29% two-year survival without urgent transplantation. Serum
      sodium level less than 132 mEq/L predicted 35% two-year survival without urgent
      transplantation. Peak oxygen consumption less than 10 mL.kg-1.min-1 identified
      poor outcome but was often not measured in patients with resting symptoms.
      CONCLUSIONS: Although definition of indications for urgent bridging requires
      complex clinical assessment based on immediate risk, it should be possible to
      identify a larger ambulatory population for whom improved devices will offer
      extended survival without transplantation.

PMID- 8561611
TI  - Mechanical bridge to transplantation: when is too early? When is too late?
AB  - BACKGROUND: Optimal timing of implantation of a mechanical circulatory support
      system in the treatment of acute cardiogenic shock is still unsettled. The issue
      has been addressed in a retrospective analysis of a group of 98 patients in
      cardiogenic shock refractory to medical therapy who were candidates for cardiac
      transplantation, admitted from 1987 to 1994. METHODS: The treatment included
      reinforced inotropic support by addition of phosphodiesterase inhibitors to
      sympathomimetic agents. The patients who did not improve were immediately brought
      to the operating room for mechanical circulatory support system implantation.
      RESULTS: The overall survival in the group of 28 patients selected for mechanical
      bridge is 50%. No predictive factors of death or multiorgan failure while on the
      device could be identified, suggesting a lack of contraindications to mechanical
      circulatory support system implantation. CONCLUSIONS: The high death rate in
      patients maintained on medical therapy because of initial improvement as they are
      awaiting transplantation suggests the benefit of a rapid semielective
      implantation of an intracorporeal device.

PMID- 8561612
TI  - Evolution of battery-powdered, vented left ventricular assist devices.
AB  - Battery-powered, vented left ventricular assist devices are designed to provide
      long-term circulatory support and an enhanced qualify of life. Their ongoing
      evolution into an effective clinical tool to treat patients with severe heart
      failure has resulted from the efforts of many, the open communication among
      researchers involved in the program, and the strong support from the National
      Institutes of Health.

PMID- 8561613
TI  - Results of extended bridge to transplantation: window into the future of
      permanent ventricular assist devices.
AB  - BACKGROUND: There is interest in expanding ventricular assist device use from
      short-term bridging to transplantation to long-term and permanent support.
      METHODS: We have reviewed the outcome of 162 patients who had as mechanical
      bridge to transplantation that lasted at least 60 days. Eighty-five patients
      received the HeartMate, 40 the Novacor, and 37 the Thoratec device. RESULTS: Of
      the 162 patients, 125 received transplants, and 115 survived after
      transplantation (93%). Within the group there were 174 complications including 54
      infections of the driveline, 73 other infections, and thromboembolic strokes in
      47. Infections of the driveline were considered major in 24 of 54 cases, and
      other infections were major in 36 of 73 cases. Twenty-seven of those who
      sustained thromboembolic events had residual effects. Of 11 patients with a major
      stroke and infection, only 1 survived transplantation. Eighty-two patients were
      supported between 60 and 100 days, 63 patients between 101 and 200 days, 12
      patients between 201 and 300 days, and only 5 patients in excess of 300 days. A
      greater percentage of candidates died waiting between 101 and 200 days than
      between 60 and 100 days (25% versus 10%). The incidence of complications also
      rose in those patients bridged more than 100 days. CONCLUSIONS: The data
      reinforce the excellent results obtained in the bridge to transplantation trials
      that reported a shorter duration of support. For those interested in extended
      bridge to transplantation or permanent use of the currently available devices,
      the results suggest reasonable success can be anticipated, but the serious
      infections and strokes tend to be more common with longer duration of support.

PMID- 8561614
TI  - Wearable long-term mechanical support for patients with end-stage heart disease:
      a tenable goal.
AB  - Increasing in frequency, and claiming more than 250,000 lives per year, heart
      failure represents a major public health problem. In spite of newer medical
      therapies, a significant proportion of patients progress to irreversible end
      stage heart disease, for which cardiac transplantation remains the only long term
      hope. The inability to meet the demand for donor organs has led to the
      development of left ventricular assist devices as a temporizing measure while
      awaiting a transplantation. The "bridging to transplantation" experience has
      firmly established the efficacy of these devices as short-term and medium-term
      mechanical assistance and has provided valuable lessons applicable to long-term
      support. Mechanical cardiac assistance technology has dramatically improved and
      can provide reliable univentricular support with minimal thromboembolic and
      infectious complications. Although major obstacles remain, the potential benefits
      are great enough and the morbidity and mortality of end-stage heart disease high
      enough to warrant the evaluation of wearable left ventricular assist devices for
      long-term mechanical assistance.

PMID- 8561615
TI  - Extended support with permanent systems: percutaneous versus totally implantable.
AB  - Use of circulatory support devices in patients awaiting heart transplantation has
      provided information about the long-term use of these devices. The Novacor left
      ventricular assist system has proved reliable for long-term support. The main
      problems with its use are infection and thromboembolism, but neither seems to
      prohibit long-term use. Problems with compliance chambers are not as great as
      previously thought. These results suggest that implantation of a permanent,
      totally implantable left ventricular assist device in lieu of transplantation is
      feasible.

PMID- 8561616
TI  - Dynamic cardiomyoplasty in South America.
AB  - BACKGROUND: Dynamic cardiomyoplasty has been proposed in the treatment of severe
      cardiomyopathies. However, few reports to date have shown significant numbers of
      patients collected on a multicenter basis. METHODS: From July 1987 to June 1994,
      dynamic cardiomyoplasty was performed in 112 patients in South America. The
      indications were dilated cardiomyopathy in 96 patients, Chagas' disease
      cardiomyopathy in 13, and ischemic cardiomyopathy in 3. Left latissimus dorsi
      muscle was used in all patients. RESULTS: The thirty-day mortality rate was 8.1%,
      and patients were followed up for 22.1 +/- 18.6 months. Data of surviving
      patients show that 47.3% were in New York Heart Association functional class I,
      45.6% in class II, and 7% in class III or IV 1 year after the operation. The 1
      year survival was 78.4%; 2-year, 59.7%; and 5-year, 41.7%. The survival at 1 year
      was 86.1% for patients with dilated cardiomyopathy and 40% for those with Chagas'
      disease. At 5 years, these values were 49.8% and 9.5%, respectively. Long-term
      survival was also significantly affected by preoperative functional class and
      pulmonary vascular resistance. However, patients operated on in class III or
      intermittent class IV and without elevated pulmonary vascular resistance had
      survival rates of 91.5% at 1 year and 76.7% at 5 years of follow-up. CONCLUSIONS:
      Cardiomyoplasty improves the functional status of patients with severe
      cardiomyopathies. Otherwise, long-term survival after this procedure is limited
      in patients with Chagas' disease and by patients' condition before the operation.

PMID- 8561617
TI  - Clinical cardiomyoplasty: review of the ten-year United States experience.
AB  - BACKGROUND: Clinical trials of dynamic cardiomyoplasty were pioneered at
      Allegheny General Hospital beginning in September 1985. Data from 9 years of
      experience with the procedure at this institution and more recent data from newer
      cardiomyoplasty centers have been analyzed for outcome analysis and future
      trends. METHODS: Each patient underwent a cardiomyoplasty procedure using the
      left or right latissimus dorsi muscle. Thirty-four patients were studied at
      Allegheny: 5 patients implanted with dual chamber pacemakers as single stimulus
      myostimulators, 11 patients composing the phase I Food and Drug Administration
      trial of the Medtronic burst myostimulator, and 18 patients entered in the phase
      II Medtronic trial. Patients from seven additional centers entered the phase II
      trial in 1991. Fifty-seven patients completed follow-up studies to 1 year after
      operation in this trial. RESULTS: Operative mortality was 5/57 (11%) in the
      American phase II group and 5/34 (15%) in the Allegheny group (1/18, 6% for
      Allegheny phase II). Nineteen patients (19/57, 33%) from the combined phase II
      population died in the first year, and 10/34 (29%) in the Allegheny study. The
      predominant cause of postdischarge death was arrhythmia (12/19, 63% American;
      7/10, 70% Allegheny). In all groups significant improvement was seen in quality
      of life and functional class. Phase II patients demonstrated significant
      increases in ejection fraction and stroke work. CONCLUSIONS: Failure to sustain
      improvement and arrhythmia-related death are complex challenges for this
      procedure; however, realistic solutions have been proposed and are under
      investigation.

PMID- 8561618
TI  - Neurologic injury in cardiac surgical patients with a history of stroke.
AB  - BACKGROUND: Controversy still exists as to whether patients with previous stroke
      are at increased risk for neurologic complications after heart operations.
      METHODS: We performed a prospective analysis of 1,000 consecutive patients
      undergoing cardiac operations requiring cardiopulmonary bypass, without
      hypothermic circulatory arrest. Of the 1,000 patients, 71 had previously
      documented stroke (study group); 2 control patients with no history of stroke
      were selected for each of these patients (control group, n = 142). There were no
      significant differences between the study and control patients with respect to
      established risk factors for neurologic complications. RESULTS: Compared with
      controls, study patients took longer to awaken (12.6 +/- 10.9 versus 3.5 +/- 2.1
      hours; p < 0.0001) and longer to extubate (29.5 +/- 29.3 versus 9.1 +/- 5.2
      hours; p < 0.001), and had a greater incidence of reintubation (7 of 71, 9.9%
      versus 2 of 142, 1.4%; p < 0.01) and postoperative confusion (26 of 71, 36.6%
      versus 7 of 142, 4.9%; p < 0.001). There was a higher incidence of focal
      neurologic deficit among study patients (31 of 71, 43.7% versus 2 of 142, 1.4%; p
      < 0.001). These deficits included new stroke (6 of 71, 8.5%) as well as the
      reappearance of previous deficits (19 of 71, 26.8%) or worsening of previous
      deficits (6 of 71, 8.5%), without new abnormalities on head computed tomography
      or magnetic resonance imaging. Study patients with neurologic deficit had longer
      cardiopulmonary bypass times than did study patients without deficit (146 +/-
      48.5 versus 110 +/- 43.3 minutes; p < 0.001). The 30-day mortality rate was
      greater in study patients than in controls (5 of 71, 7% versus 1 of 142, 0.7%; p
      < 0.02), with four deaths among the 6 study patients with a new stroke (66.7%).
      CONCLUSION: This analysis identifies a group of patients at high risk for
      neurologic sequelae and confirms the vulnerability of the previously injured
      brain to cardiopulmonary bypass, as evidenced by reappearance or exacerbation of
      focal deficits in such patients.

PMID- 8561619
TI  - Aortomyoplasty counterpulsation: experimental results and early clinical
      experience.
AB  - BACKGROUND: Presently the only clinical method of skeletal muscle augmentation of
      the heart is achieved by wrapping muscle around the cardiac ventricles and then
      stimulating the muscle to contract synchronously with cardiac systole.
      Intraaortic balloon counterpulsation provides diastolic counterpulsation in the
      short-term with the known benefits of increasing diastolic pressure and reducing
      ventricular afterload. Using protocols already in existence for dynamic
      cardiomyoplasty we have investigated the long-term use of extraaortic skeletal
      muscle-powered counterpulsation. METHODS: In five alpine goats the right
      latissimus dorsi muscle (LDM) was used to achieve a wrap around the ascending
      aorta, which had been augmented with an elliptic pericardial patch.
      Electrostimulation protocols were commenced after 2 weeks and continued for 12 to
      24 months. At this time baseline hemodynamic measurements were made with and
      without stimulation of the LDM. Acute cardiac depression was induced and further
      measurements were made, again with and without stimulation of the LDM. RESULTS:
      Results in the basal state demonstrated improvement in all parameters with
      stimulation and a 23% increase of the subendocardial viability index. After
      induction of cardiac depression there was a 52% increase in cardiac output, 39%
      decrease in systemic vascular resistance, and 27% increase in subendocardial
      viability index. Histologic studies demonstrated tight adhesion between the
      aortic wall and the LDM, no dilatation of the aortic wall, and no deleterious
      effects in the aortic wall of the chronic intermittent constriction.
      Histochemical staining demonstrated transformation of the muscle fibers of the
      LDM flap into type 1 oxidative muscle fibers. CONCLUSIONS: In conclusion, our
      present study demonstrates that in this animal model aortomyoplasty produces a
      chronic counterpulsation with preservation of aortic architecture. With induction
      of heart failure aortomyoplasty provided an effective means of cardiac
      assistance. The use of the ascending aorta to achieve diastolic counterpulsation
      may be an efficient use of skeletal muscle energy to augment the heart in
      selected clinical cases. Early clinical experience is described in this article.

PMID- 8561620
TI  - Regional effects of aortomyoplasty in acute ischemia.
AB  - BACKGROUND: Aortomyoplasty is a technique for achieving autogenous diastolic
      counterpulsation. This experiment was designed to determine if aortomyoplasty
      using conditioned latissimus dorsi muscle could improve regional myocardial
      function during coronary ischemia. METHODS: Six mongrel dogs underwent a staged
      operation in which the left latissimus dorsi was conditioned in situ for 4 weeks,
      then wrapped around the descending aorta and stimulated during diastole with each
      cardiac contraction. Regional ischemia was caused by occlusion of the left
      anterior descending coronary artery. Regional function was measured with
      somomicrometry in the region of ischemia and in a control area. An intraaortic
      balloon pump was inserted for comparison with aortomyoplasty performance.
      RESULTS: Coronary artery occlusion caused a significant decrease in the
      percentage of regional shortening (14.2 +/- 7.9 to -2.2 +/- 4.0; p = 0.001) and
      thickening (11.9 +/- 4.6 to -5.8 +/- 3.3; p < 0.001). Aortomyoplasty improved
      regional motion in both percentage shortening (-2.2 +/- 4.0 to 2.3 +/- 3.7; p =
      0.008) and thickening (-5.8 +/- 3.3 to 2.8 +/- 1.9; p < 0.001). The intraaortic
      balloon pump also improved percentage shortening (-3.7 +/- 2.0 to 0.7 +/- 1.9; p
      = 0.01) and thickening (-5.0 +/- 2.8 to 2.4 +/- 3.8; p < 0.001), and was not
      significantly different than aortomyoplasty. CONCLUSIONS: These data show that
      aortomyoplasty has beneficial effects on ischemic left ventricular contractility,
      and may therefore be useful for treating inoperable coronary artery disease.

PMID- 8561621
TI  - Skeletal muscle ventricles in circulation: decreased incidence of rupture.
AB  - BACKGROUND: Skeletal muscle ventricles (SMVs) are muscular pumping chambers
      constructed for cardiac assist. Skeletal muscle ventricles can be connected to
      the circulation in a variety of configurations for both left and right heart
      assist; when connected to the aorta and stimulated to contract during diastole,
      they function in a similar fashion as an intraaortic balloon pump. METHODS:
      Skeletal muscle ventricles were constructed in 18 dogs using the left latissimus
      dorsi muscle. In 10 of these dogs (group 1), the inner surface of the SMV was
      lined with autogenous pericardium obtained at the time of construction of the
      SMV. For the remaining 8, the SMVs were lined by fibrous tissue that forms in
      reaction to the synthetic mandrel around which the latissimus muscle is wrapped.
      After the muscles were electrically conditioned to a fatigue-resistant state, the
      mandrels were removed from the SMVs and the SMVs were connected to the descending
      thoracic aorta with a specially constructed base cap and two
      polytetrafluoroethylene conduits. RESULTS: Initial hemodynamic recordings
      revealed that the mean diastolic blood pressure increased by 24.7% in group 1 and
      by 29.8% in group 2. Diastolic augmentation was well maintained over time;
      augmentation in surviving group 1 animals was 30.0% after 18 months of pumping
      continuously in circulation. Long-term survival was greater in the dogs whose
      SMVs were constructed using an inner pericardial lining. At 90 days in
      circulation, 60% of the dogs in group 1 were alive with functioning SMVs, whereas
      only 13% of the dogs in group 2 were alive. The incidence of SMV rupture in the
      fibrouslined SMVs was 63%, whereas the incidence in the pericardial-lined SMVs
      was 0%. No evidence of thromboembolism occurred in either group. CONCLUSIONS:
      Lining the inner surface of an SMV with pericardium appears to provide structural
      integrity, which helps to prevent the complication of SMV rupture in this model
      of cardiac assist.

PMID- 8561622
TI  - Pierce-Donachy pediatric VAD: progress in development.
AB  - BACKGROUND: Despite the successful use of ventricular assist devices in adults
      over the past 15 years, relatively little has been done to develop similar
      devices for pediatric patients. Consequently, no such device is currently
      available. A review of clinical data suggests that the majority of patients in
      need of a pediatric ventricular assist device, either for postcardiotomy
      cardiogenic shock or as a bridge to cardiac transplantation, are neonates
      weighing 3 to 5 kg. Attempts to "scale down" an adult blood pump to make an
      appropriate device for these patients have been difficult due to the lack of
      sufficiently small, commercially available valves and the tendency for thrombus
      to develop in these small pumps. METHODS: We report on progress in the
      development of the Pierce-Donachy pediatric ventricular assist device, which
      incorporates 10-mm-diameter bileaflet valve prototypes. Particle image
      velocimetry is used to quantify the velocity field inside the pump. RESULTS AND
      CONCLUSIONS: Particle image velocimetry velocity maps demonstrate the complexity
      of the flow patterns in these pumps and suggest that improved flow patterns may
      result from the use of valves with improved hemodynamic performance. Animal tests
      to determine whether improved flow patterns and better "washing" of the pump's
      blood-contacting surfaces will reduce thrombus formation are underway.

PMID- 8561623
TI  - Totally implantable intrathoracic ventricular assist device.
AB  - BACKGROUND: A totally implantable, intrathoracic electrohydraulic ventricular
      assist device (EVAD) is being developed for permanent use or as a bridge to
      transplantation. METHODS: The blood pump with 70-mL nominal stroke volume, volume
      displacement chamber, reversible turbine, internal electronics and infrared
      diaphragm position sensor are combined in one compact unit (unified system). The
      size and geometry are based on human anatomic measurements and fluid dynamic
      studies. A transcutaneous energy transfer powers the system and recharges the
      implantable nickel-cadmium battery pack. Autotuning circuitry optimizes energy
      transfer efficiency over a range of transcutaneous energy transfer coil spacings
      and misalignments. An infrared diaphragm position sensor detects end-systole and
      diastole points. RESULTS: In vitro and acute in vivo tests have demonstrated flow
      rates greater than 6 L/min. The transcutaneous energy transfer system
      demonstrated power transfer efficiencies of 60% to 80% for power demands from 5
      to 60 W. Thirteen systems are currently undergoing durability testing; one has
      run for more than 750 days failure-free. The system recently sustained
      circulation in an acute calf implantation for 96 hours. CONCLUSIONS: Results of
      the in vitro and in vivo testing to date have demonstrated that the developed
      system can function effectively as a totally implantable ventricular assist
      device. Chronic in vivo evaluation is planned.

PMID- 8561624
TI  - Development and initial testing of a pediatric centrifugal blood pump.
AB  - BACKGROUND: We are developing a miniaturized centrifugal blood pump for use as a
      temporary cardiac assist device in neonatal and pediatric sized patients. This
      pump has a very low priming volume of 13 mL. A small motor stator has also been
      designed, which resulted in a device that can be placed very close to the
      patient, thereby minimizing overall circuit volume. METHODS: Testing to date has
      included in vitro hemodynamic performance, in vitro hemolysis generation, and in
      vivo evaluation in 5 lambs weighing 5.5 to 21 kg. Two lambs underwent peripheral
      cannulation from external jugular vein to carotid artery, whereas 3 others were
      cannulated from left atrium to carotid artery. RESULTS: In vitro data
      demonstrated pump capacity spanning 0.3 to 3.0 L/min and very low hemolysis
      generation at these conditions. In vivo, the pump functioned satisfactorily for
      periods up to 148 hours, and the bypass appeared to be well tolerated by the
      animals. Plasma free hemoglobin levels remained less than 25 mg/dL during all
      animal experiments. All devices were thrombus-free at explantation. CONCLUSIONS:
      We conclude that this device has merit as an alternative to current oversized
      systems used for neonatal and pediatric cardiac assistance. In addition, a
      chronic neonatal lamb model in which to evaluate pediatric circulatory assist
      devices has been developed successfully.

PMID- 8561625
TI  - Small, low-cost implantable centrifugal pump for short-term circulatory
      assistance.
AB  - BACKGROUND: In 1991, Allegheny General Hospital and Allegheny-Singer Research
      Institute purchased a centrifugal pump, then a 2-year-old technology, from
      Medtronic Bio-Medicus, as part of its research program for novel treatments of
      acute and chronic heart failure. During a 4-year development program, we then
      established and met goals of durability, performance, thromboresistance, and low
      cost. METHODS: In vitro testing involved extensive hydraulic characterizations
      using Penn State mock loops. Calorimetry was used to determine efficiency.
      Durability studies used heated (37 degrees C) seawater for 28 to 45 days. In vivo
      studies used 46 sheep to test performance and engineering changes and to
      determine myocardial oxygen consumption, thromboresistance, and long-term
      durability. A left atrium-to-aorta circuit was used in all. RESULTS: Hydraulic
      testing showed no preload sensitivity but moderate afterload sensitivity at all
      impeller speeds (2,000 to 6,000 rpm). The heat load was low, and overall
      efficiency was 13% to 15%. Bench durability studies showed no electrical
      malfunction of the stator or console without degradation of the biomaterials
      used. Acute in vitro studies showed a near-linear relationship of myocardial
      oxygen consumption and left ventricular stroke work, pump flow, and pump speed.
      At speeds of 2 to 3 L/min (50% bypass), left ventricular stroke work and
      myocardial oxygen consumption were decreased approximately 50%. Additionally, 5
      animals have had implants for 28 to 154 days with no macroemboli or microemboli
      detected in any animal. Hematologic and biochemical studies became normal 3 to 7
      days after implantation. Hemolysis was low at less than 10 mg/dL. Clinical costs
      of the device are estimated to be 80% less than those of currently available
      devices. CONCLUSIONS: We conclude that an old technology has been made into new
      technology by application of sound engineering design principles, microchips, and
      new biomaterials. Qualifying trails for a Food and Drug Agency investigational
      device exemption application are in progress.

PMID- 8561626
TI  - Cleveland clinic rotodynamic pump.
AB  - BACKGROUND: It is now accepted that 70% to 80% of patients with end-stage heart
      failure would benefit from a permanent implanted left ventricular assist device.
      Previously there was little consideration of the use of nonpulsatile pumps for
      this function. METHODS: An extensive 5-year engineering research and development
      program to develop a permanent implanted nonpulsatile blood pump has been
      undertaken. RESULTS: We have developed a continuous-flow blood pump of small size
      (207 g) and low power requirement (6.5 watts) producing 5 L/min flow with low
      hemolysis. CONCLUSIONS: This pump has the potential to be the basis of an
      innovative ventricular assist system.

PMID- 8561627
TI  - Cora valveless pulsatile rotary pump: new design and control.
AB  - For decades, research for developing a totally implantable artificial ventricle
      has been carried on. For 4 to 5 years, two devices have been investigated
      clinically. For many years, we have studied a rotary (but not centrifugal) pump
      that furnishes pulsatile flow without a valve and does not need external venting
      or a compliance chamber. It is a hypocycloidal pump based on the principle of the
      Maillard-Wankel rotary compressor. Currently made of titanium, it is activated by
      an electrical brushless direct-current motor. The motor-pump unit is totally
      sealed and implantable, without noise or vibration. This pump was implanted as a
      left ventricular assist device in calves. The midterm experiments showed good
      hemodynamic function. The hemolysis was low, but serious problems were
      encountered: blood components collecting on the gear mechanism inside the rotor
      jammed the pump. We therefore redesigned the pump to seal the gear mechanism. We
      used a double system to seal the open end of the rotor cavity with components
      polished to superfine optical quality. In addition, we developed a control system
      based on the study of the predicted shape of the motor current. The new design is
      now underway. We hope to start chronic experiments again in a few months. If the
      problem of sealing the bearing could be solved, the Cora ventricle could be used
      as permanent totally implantable left ventricular assist device.

PMID- 8561628
TI  - Nursing experience with the VAD patient: what's hot and what's not.

PMID- 8561629
TI  - Nursing experience with the VAD patient: what's hot and what's not.

PMID- 8561630
TI  - Clinical problem solving: multidisciplinary case review.

PMID- 8561631
TI  - Discharging patients who are undergoing mechanical circulatory support.
AB  - Six patients supported by the Baxter Novacor left ventricular assist system have
      been discharged during the period of mechanical circulatory support at the
      University of Pittsburgh Medical Center. Benefits of discharge couple quality of
      life improvements and economic advantages for mechanical circulatory support
      patients. Limitations caused by regulations within current protocols have been
      shown to detract from patient and caregiver quality of life. Eliminating the
      unnecessary regulations will improve discharge capabilities without increasing
      the risk for clinical complications.

PMID- 8561632
TI  - Pressure gradients across bileaflet aortic valves by direct measurement and
      echocardiography.
AB  - BACKGROUND: Pressure gradients calculated from echo-cardiography after aortic
      valve replacement are commonly much higher than would be expected from in vitro
      measurements. METHODS: The mean, peak-to-peak, and maximal gradients across
      bileaflet aortic prostheses (St. Jude Medical) were measured invasively in 52
      patients at high and low heart rate, cardiac index, and stroke volume. One week
      after operation the gradients were calculated from a standard transthoracic
      echocardiogram (delta p = 4v2(2)). In a second study 3 to 12 months later,
      gradients were calculated using the standard, simplified Bernoulli equation, and
      with the equation considering subvalvular flow velocities (delta p = 4(v2(2
      )v1(2)). Invasive and echocardiographic measurements were matched and compared.
      RESULTS: Invasively measured mean gradients for 21 to 29-mm valves ranged from
      7.4 +/- 4.9 to 4.3 +/- 1.6 mm Hg at systolic flow rates from 11.3 +/- 0.7 to 16.2
      +/- 1.8 L.min-1.m-2. Mean echocardiographic gradients were 15.1 +/- 4.5 to 7.5 +/
      2.2 mm Hg (p < 0.001) with the standard method, and 10.5 +/- 1.9 to 5.6 +/- 1.5
      mm Hg when considering the subvalvular flow velocity (p < 0.001). CONCLUSIONS:
      Mean gradients across bileaflet prostheses are generally low, even in small
      valves and with high systolic flow. The correlation of the invasive in vivo with
      in vitro gradients is good. Standard echocardiography overestimates gradients
      across bileaflet heart valves and high gradients are not due to valve
      dysfunction. Gradients obtained by echocardiography considering the subvalvular
      flow velocity correlate better to invasively measured and in vitro gradients.

PMID- 8561633
TI  - Clinical problem-solving: multidisciplinary case review.

PMID- 8561634
TI  - FDA regulation of medical devices. FDA perspective.
AB  - In this article, based on a presentation before The Society of Thoracic Surgeons,
      D. Bruce Burlington, MD, director of the United States Food and Drug
      Administration's Center for Devices and Radiological Health, describes the role
      of the Center in regulating medical devices. Doctor Burlington discusses issues
      concerning investigational device exemptions and development of protocols,
      marketing review for new products, the use of guidance by the agency in
      developing products, and humanitarian device provisions. He focuses this
      discussion on circulatory support devices and therapies for cardiac patients.
      Throughout the discussion, Dr Burlington encourages manufacturers of new devices
      to discuss their plans and protocols with the agency before beginning their
      studies.

PMID- 8561635
TI  - Industry perspective on FDA regulation of medical devices and the practice of
      medicine.

PMID- 8561636
TI  - Point/counterpoint, legal perspective.

PMID- 8561637
TI  - Point/counterpoint, surgical aspect.

PMID- 8561638
TI  - Modified Blalock-Taussig shunt using allograft saphenous vein: six years'
      experience.
AB  - BACKGROUND: The occurrence of life-threatening late infectious complications
      after the use of expanded polytetrafluoroethylene conduits as modified Blalock
      Taussig shunts prompted us to apply allograft saphenous veins instead. METHODS:
      In 23 cyanotic patients (age, 1 week to 18 years) allograft saphenous veins were
      used for performing Blalock-Taussig shunts from July 1989 onward. Veins stored in
      Hank's solution were implanted in 8 patients and cryopreserved ones in 15. All
      patients were followed up regularly up to 15 months. RESULTS: There were two
      early and two late deaths: none were related to shunt occlusion. Clinical,
      angiographic, and echocardiographic studies proved that, except for one early
      occlusion, all shunts were patent and functioning well after an average of 41
      months. Donor cells disappeared 1 to 3 days after implantation, and several
      months after the operation both the wall and the luminal surface of the grafts
      were repopulated with cells possibly of recipient origin. No difference was found
      between veins stored in Hank's solution only and cryo-preserved grafts,
      concerning clinical outcome and histology. CONCLUSIONS: Allograft saphenous veins
      function well as modified Blalock-Taussig shunts at least up to 6 years. Owing to
      the good results and lack of complications their clinical use is recommended.

PMID- 8561639
TI  - The tyranny of managed care.

PMID- 8561640
TI  - Coronary artery bypass grafting without cardiopulmonary bypass.
AB  - BACKGROUND: Coronary artery bypass grafting without cardiopulmonary bypass is now
      an accepted technique of myocardial revascularization. We herein report our total
      experience with this procedure. METHODS: In a consecutive series of 8,751
      patients operated on in our institution for coronary artery disease from 1981 to
      1994, 1,274 patients received coronary artery bypass grafting without
      cardiopulmonary bypass. RESULTS: Results indicate that the operation can be
      performed with an acceptable mortality (2.5%), and that all types of arterial
      conduits can be used. Most commonly the left anterior descending and right
      coronary arteries were bypassed. The incidence of arrhythmias and of pulmonary
      and neurologic complications were significantly lower in this group of patients
      compared with patients receiving coronary artery bypass grafting with
      cardiopulmonary bypass. Most importantly, there was decreased cost when the
      procedure was used because no extracorporeal circulation, cardioplegia sets, or
      other cannulas were used. CONCLUSIONS: We conclude that the continuing use of
      coronary artery bypass grafting without cardiopulmonary bypass is justified and
      that, with proper selection of patients, the procedure is safe and cost
      effective.

PMID- 8561641
TI  - St. Thomas' Hospital cardioplegia: enhanced protection with exogenous creatine
      phosphate.
AB  - BACKGROUND: Experimentally, creatine phosphate (CP) improves postischemic
      recovery of function and reduces postischemic arrhythmias. METHODS: We studied 50
      patients undergoing valve replacement. They were randomized into either a control
      group, who received St. Thomas' Hospital cardioplegic solution No. 1, or a CP
      treated group, receiving the same cardioplegic solution plus CP (10 mmol/L).
      There were no preoperative clinical differences between groups. Assessment was by
      electrocardiographic analysis, inotropic drug requirement, quantitative
      birefringence, myocardial high-energy phosphate content, function, and
      semiquantitative ultrastructural assessment. RESULTS: Direct-current shocks were
      reduced in the CP-treated group (0.88 +/- 0.15) compared with the control group
      (1.40 +/- 0.14; p < 0.02), as was the total number of joules (22.0 +/- 3.5 versus
      34.4 +/- 3.7, respectively; p <0.02). The incidence of spontaneous sinus rhythm
      was higher in the CP-treated group (40% versus 8%; p < 0.05) and the incidence of
      postoperative arrhythmias, lower (8% versus 32%; p < 0.05). Prolonged inotropic
      administration (12 hours or longer) occurred in fewer patients in the CP-treated
      group (4% versus 28%; p < 0.05). Response to inotropic support (in the subset of
      patients requiring this treatment) was significantly greater in the CP-treated
      group than in the control group. There were no differences in recovery of
      function, birefringence changes, myocardial high-energy phosphate content, or
      ultrastructure between groups. CONCLUSIONS: St. Thomas' Hospital cardioplegic
      solution No. 1 plus CP enhanced myocardial protection and conferred a direct
      benefit to the patient by reducing postoperative arrhythmias and need of
      prolonged inotropic support.

PMID- 8561642
TI  - Beneficial effects of Duraflo II heparin-coated circuits on postperfusion lung
      dysfunction.
AB  - BACKGROUND: Heparin coating of the cardiopulmonary bypass circuit reduces the
      activation of the terminal part of the complement cascade. Conflicting data are
      reported concerning neutrophil activation and postoperative lung dysfunction. In
      this study, we compared three different types of oxygenator: a bubble oxygenator,
      a conventional hollow-fiber oxygenator, and a heparin-coated oxygenator and
      circuit. METHODS: Sixty patients undergoing myocardial revascularization were
      randomly assigned to one of three oxygenator groups. All the patients were free
      from preoperative lung dysfunction. Lung function was studied with repeated
      measurements of respiratory index, intrapulmonary shunt, alveolar dead space,
      ventilation/perfusion ratio, and static thoracopulmonary compliance. RESULTS:
      Immediately after cardiopulmonary bypass, the intrapulmonary shunt and
      respiratory index values in the bubble oxygenator and hollow-fiber oxygenator
      groups increased more than those in the heparin-coated oxygenator group. In the
      intensive care unit, the between-group difference in intrapulmonary shunt
      disappeared, but the within-group difference in respiratory index (from baseline)
      remained for the bubble oxygenator group. The other three variables did not
      significantly differ between groups. Intubation time and stay in the intensive
      care unit did not differ between groups. CONCLUSIONS: Heparin-coated circuits
      exert a protective effect on pulmonary function. However, their use did not
      modify the postoperative clinical course of patients with normal lung function
      preoperatively.

PMID- 8561643
TI  - Stratifying patients preoperatively for transfusion outcomes.

PMID- 8561644
TI  - Neonatal myocardial oxygen consumption during ventricular fibrillation,
      hypothermia, and potassium arrest.
AB  - BACKGROUND: Many investigators have examined oxygen consumption in adult heats
      under conditions that simulate those encountered during cardiac operations and
      those that approximate basal metabolism. Few studies, however, have addressed
      this issue in neonatal myocardium. METHODS: Hearts from 3- to 9-day-old piglets
      were studied in a blood-perfused isolated heart preparation in working, empty
      beating, fibrillating, potassium chloride-arrested (at 37 degree C and 15 degree
      C), and hypothermic (15 degree C) states. RESULTS: Oxygen consumption (expressed
      in milliliters of O2 per 100 g of ventricular tissue per minute; mean +/-
      standard deviation) was 6.69 +/- 1.91 for working hearts and fell to 3.19 +/-
      1.08 for empty-beating hearts, 3.72 +/- 0.84 for fibrillating hearts, 1.30 +/-
      0.34 for potassium-arrested hearts at 37 degree C, 0.37 +/- 0.18 for hypothermic
      (15 degree C) hearts, and 0.32 +/- 0.10 for potassium-arrested hearts at 15
      degree C. All values were significantly different except the two obtained at 15
      degree C. CONCLUSIONS: Vented fibrillating hearts used more oxygen than empty
      beating hearts. The addition of an arresting concentration of KCl did not lower
      oxygen consumption below that observed with hypothermia alone at 15 degree C. If
      potassium-based cardioplegia is incrementally beneficial in neonatal myocardial
      protection over that afforded by hypothermia alone, its effects cannot be
      explained by reduction in oxygen demand.

PMID- 8561645
TI  - Serum S100 protein: a potential marker for cerebral events during cardiopulmonary
      bypass.
AB  - BACKGROUND: There is no simple method to determine the incidence or severity of
      brain injury after a cardiac operation. A serum marker equivalent to cardiac
      enzymes is required. S100 protein leaks from the cerebrospinal fluid to blood
      after cerebral injury. We sought to determine the pattern of release after
      extracorporeal circulation (ECC). METHODS: Thirty-four patients without
      neurologic problems underwent coronary bypass using ECC. Four had carotid
      stenoses. Nine others underwent coronary bypass without ECC. Serum S100 levels
      were measured before, during, and after the operation. RESULTS: S100 was not
      detected before sternotomy. Postoperative levels of S100 were related to duration
      of perfusion (r = 0.89, p < 0.001). Patients who did not have ECC had
      undetectable or fractionally raised levels except in 1 who suffered a stroke. No
      patient in whom ECC was used suffered an event, but those with carotid stenosis
      had greater S100 levels. CONCLUSIONS: S100 protein leaks into blood during ECC
      and may reflect both cerebral injury and increased permeability of the blood
      brain barrier. S100 is a promising marker for cerebral injury in cardiac surgery
      if elevated levels can be linked with clinical outcome.

PMID- 8561646
TI  - Descending thoracic aortomyoplasty: a technique for clinical application.
AB  - BACKGROUND: Descending thoracic aortomyoplasty is a form of skeletal muscle
      powered cardiac assistance. Its use in clinical settings has been limited by the
      ligation of intercostal arteries necessary to complete a circumferential wrap of
      the aorta with the latissimus dorsi. METHODS: This study assessed the feasibility
      and the efficacy of aortomyoplasty constructed with a modified latissimus dorsi.
      A pericardial patch was attached to the latissimus dorsi and divided around the
      preserved intercostal arteries. Nine alpine goats (37 +/- 2 kg) underwent
      descending aortomyoplasty using this technique. All intercostal arteries were
      preserved. After a 6-week recovery period, the animals underwent a 6-week,
      incremental electrical conditioning program. After 90 postoperative days, animals
      were examined under anesthesia with the myostimulator on and off. RESULTS:
      Aortomyoplasty activation resulted in augmentation of mean diastolic aortic
      pressure by 16.0 +/- 0.9 mm Hg (23%). Significant improvements in cardiac index
      (40%), stroke volume index (37%), left ventricular stroke work index (49%), and
      mean arterial pressure (19%) were noted. An intravascular sonographic probe
      placed in the descending aorta revealed circumferential compression of the aorta
      during counterpulsation. Mean cross-sectional aortic area was reduced by 51.8%,
      from 210.1 +/- 7.1 to 108.9 +/- 6.7 mm2 during aortomyoplasty activation (p <
      0.05). Histologic analysis confirmed the long-term patency of intercostal
      arteries. CONCLUSIONS: Descending aortomyoplasty, modified with an interposing
      patch of pericardium, effectively transfers skeletal muscle force across the
      aortic wall and assists cardiac function. This technique allows preservation of
      all aortic branches, and with this novel approach, the clinical utility of
      aortomyoplasty can now be explored.

PMID- 8561647
TI  - Mycoplasma hominis infections occurring in cardiovascular surgical patients.
AB  - BACKGROUND: Postoperative Mycoplasma hominis sternal would or mediastinal
      infections are uncommon and difficult to diagnose. Atypical growth
      characteristics in routine bacterial culture, and the inability to demonstrate
      the organism on Gram stain, lead to delayed diagnosis of M hominis infections and
      increased morbidity. METHODS: Postoperative purulent would drainage or acute
      mediastinitis caused by M hominis developed in 3 cardiovascular surgery patients.
      These patients were considered along with 9 patients previously reported in the
      literature. RESULTS: Operative findings included moderately thick, gray purulent
      fluid with the degree of tissue necrosis related to duration of infection.
      Intraoperative Gram stain of wound or mediastinal drainage demonstrated no
      microorganisms, and initial bacterial cultures did not reveal microbial growth.
      After an average of 4.5 days of culture, minute translucent colonies of M hominis
      were identified. The institution of appropriate antimycoplasma therapy
      (doxycycline and clindamycin) was associated with clinical or microbiological
      cure in all patients. Sternal wound complications developed in 3 patients, and a
      chronic infection developed in 1 patient. CONCLUSIONS: Empiric therapy for M
      hominis infection should be considered in patients with mediastinitis or a
      sternal wound infection in which organisms are not observed on Gram stain and are
      not readily cultured.

PMID- 8561648
TI  - [In memory of Professor Ignacio Chavez (1897-1979) on the 16th anniversary of his
      death (July 1979)].

PMID- 8561649
TI  - [Myocardial viability].

PMID- 8561650
TI  - [Evaluation of the toxicity of indorenate on reproduction].
AB  - Indorenate (TR3369) a new antihypertensive drug, was examined for effects upon
      general reproductive performance, for peri-postnatal and embryofetal toxicity in
      the rat at doses of 0, 10, 20, 40 and 60 mg/kg/day by oral administration.
      Excluding the 60 mg/kg dose, in the fertility study, any dose produced neither
      decrement of body weight gain of progenitors, fertility, fetal weight nor
      survival rate. Retardation of the surface righting, pinnal unfolding or startle
      response were not observed. On the other hand, 40 and 60 mg/kg significantly
      increased the number of resorptions. In the peri-postnatal study, doses of 40 and
      60 mg/kg incremented the number of dead pups at birth, and the later also
      affected the survival rate, growing and air righting reflex. Reproductive
      performance of the F1 offsprings was unimpaired. Indorenate in contrast to
      serotonin, from which it is a structural derivative, gave no evidence of
      teratogenicity when administered during the period of organogenesis. It was
      concluded that the parameters of fetal development were not affected by doses of
      up to 20 mg/kg, which represents approximately 1200 times the proposed dose for
      hypertensive patients.

PMID- 8561651
TI  - [Percutaneous coronary angioscopy: 200 observations in 100 candidates for
      angioplasty].
AB  - Due to the recent technological advances, it is possible to perform percutaneous
      coronary angioscopy in a straightforward fashion in most patients. To know the
      safety and usefulness of this technique we present 200 observations in 100
      patients candidates for coronary intervention. We used a coronary angioscope
      (Baxter, Edwards LIS Division), that can be placed using the conventional
      technique for percutaneous coronary angioplasty. The system incorporates a
      proximal occluding balloon, and distally a movable optical fiber. Case selection
      considered non-ostial coronary segments relatively straight. It was possible to
      obtain adequate images in 86 percent of cases. The technique is safe in
      experienced hands: there were two cases of ventricular fibrillation, and two
      cases of local dissection occurred, none of these associated with clinical
      consequences. No myocardial infarction, surgery or death, related to this
      procedure occurred. Valuable diagnostic information is derived from angioscopy as
      the method provides some histopathological correlation. Stable plaques are
      usually uniformly white or yellow. Unstable plaques are yellow and ulcerated.
      Thrombus can be easily recognized in acute coronary syndromes. Also in
      percutaneously treated segments, the final result and the presence of dissection
      or hemorrhage can be visualized. Coronary percutaneous angioscopy is safe and
      brings useful clinical information. Its applications in the clinical practice are
      still to be determined.

PMID- 8561652
TI  - [Risk factors for ischemic heart disease in Mexico: a case control study].
AB  - A case control study was developed in order to assess the strength of the
      association of modifiable risk factors and the occurrence of coronary heart
      disease in Mexicans. A total of 284 incident cases of acute myocardial infarction
      and 284 age and sex matched hospitalized controls were included in the study.
      Information was obtained in all subjects regarding socio-demographic variables,
      history of diabetes, hypertension, smoking, obesity and serum cholesterol. A
      conditional logistic regression model, showed that diabetes mellitus,
      hypertension, smoking, hypercholesterolemia and obesity, explained the occurrence
      of coronary heart disease in the studied population. The risk of an acute
      myocardial infarction heavily increases in the extreme levels of exposure; and
      this risk is six fold higher in those who daily smoke more than 20 cigarettes,
      and it is eight fold higher in those subjects with a serum cholesterol greater
      than 240 mg/dl. Due to the increase in the occurrence of coronary heart disease
      in Mexico, and the strength of the association observed with these modifiable
      risk factors, a public health program to decrease its prevalence, is justified.

PMID- 8561653
TI  - [Rescue thrombolysis with repeated doses of streptokinase in acute myocardial
      infarct. A preliminary report].
AB  - In patients with persistent acute ischemia and early reocclusion after
      thrombolytic therapy, the available therapeutic options are optimum drug
      pharmacologic treatment or a mechanical revascularization. Recently, repeated
      doses of the same thrombolytic agent used (rescue thrombolysis) have been
      considered. We report our experience in seven patients with acute myocardial
      infarction treated with conventional streptokinase dose, within the first 6 hs
      after onset of the symptoms, and whom due to persistent myocardial ischemia or
      early reocclusion, hemodynamic instability, significative area of myocardium at
      risk, failure of maximal doses of conventional therapeutic and inaccessibility
      for performed mechanical revascularization, a second dose of streptokinase was
      successfully employed in the early (1:45 to 2:30 hs) and late (48 to 50:00 hs)
      phase, without hemorrhagic complications and without hypersensitivity effects. In
      every case rescue thrombolysis allowed to limit the time of ischemia and the
      extension of the myocardial infarction, demonstrated by indirect clinical
      criteria, improvement in hemodynamic instability and in the ventricular ejection
      fraction, that can be considered as a postinfarction myocardial function index,
      as well as by the reduced in-hospital mortality. These findings suggest that in
      patients with acute myocardial infarction treated with thrombolytic therapy, and
      persistent acute ischemia or early reocclusion, a second dose of streptokinase
      could be a safe and effective therapeutic option. Our successful results will
      lead to a prospective trial.

PMID- 8561654
TI  - [Diagnosis of myocardial ischemia by dynamic digital echocardiography with
      dobutamine and atropine].
AB  - We studied 300 patients (p) with dobutamine stress echocardiography (DSE) and
      atropine. The indication were chest pain, abnormal electrocardiogram (ECG),
      abnormal stress electrocardiogram with or without chest pain or any combination
      of these. The DSE was evaluated with digitized imaging in long and short
      parasternal views and apical four and two chambers views before and during
      dobutamine test with simultaneous side by side display. In 21 p (56.7%) we found
      positive concordance in diagnosis of coronary artery disease (CAD) between
      coronary arteriography (CA) and DSE. In 13 of 37 p the concordance was negative
      by the two methods (35.1%); then the DSE was capable correctly predict in 34 p
      (91%). The abnormal CA and normal DSE were found in one p (4.5%) with 90%
      obstruction of a small diagonal vessel. In two women DSE was abnormal with
      inferior hypokinesis (13.3%) and the CA was normal. In 43 p (14.3%) ECG and DSE
      were positive for myocardial ischemia (MI); negative concordance of both
      procedures was found in 203 p (67.6%). ECG was abnormal and DSE normal in 46 p
      (15.3%) 61 p (20.3%) with DSE abnormal in 8 p (2.6%) 61 p (20.3%) had
      arrhythmias; in 55 (18.3%) premature ventricular contractions, one p with
      ventricular tachycardia (0.33%); 7.3% of them required endovenous lidocaine.
      Chest pain was present in 22 p (7.3%) and the treatment waqs sublingual
      isosorbide; hypotension appeared in 27 p (9%) and were treated with saline
      infusion. Hypertensive response was found in two p (0.66%) and were treated with
      nifedipine and smolol. We concluded that DSE with atropine has high sensibility
      (95.5%) and specificity (86.6%) in the diagnosis of ischemic heart disease. The
      adverse effects are nondangerous and easily resolved with medical treatment.

PMID- 8561655
TI  - [Effects of avocado on the level of blood lipids in patients with phenotype II
      and IV dyslipidemias].
AB  - To examine the effects of avocado on plasma lipid concentrations a two-diet trial
      involving 8 phenotype IV and 8 phenotype II dyslipidemia patients was carried
      out. A diet rich in monounsaturated fatty acids (DRCA) using the avocado as their
      major source (30% of the total calories were consumed as fat, 75% of the total
      fat from the avocado), with restriction of saturated fat and less of 300 mg of
      cholesterol per day was evaluated. Patients also were in a low-saturated fat diet
      without avocado (DRSA). The three daily meals were eaten at our clinical unit.
      Diets were four weeks in duration and they were assigned in a crossover design.
      In phenotype II both DRCA and DRSA significantly reduced total cholesterol and
      LDL-cholesterol levels. On phenotype IV DRCA produced a mild reduction on
      triglyceride levels while DRSA increased them. On HDL-cholesterol concentrations
      DRCA produced a significant increase in both phenotypes while DRSA did it only in
      phenotype IV. Avocado is an excellent source of monounsaturated fatty acids in
      diets designed to treat hypercholesterolemia with some advantages over low-fat
      diets with a greater amount of carbohydrates.

PMID- 8561656
TI  - [Transcatheter closure of patent ductus arteriosus with Rashkind's occluder.
      Experience during 3.7 years].
AB  - Thirty eight transcatheter umbrella closure (TUC) of a persistently patent ductus
      arteriosus using the Rashkind umbrella occluder (USCI), were attempted in thirty
      four patients. Mean age 8.5 +/- 9.0 years (range 1.5 to 31). Internal diameter of
      ductus arteriosus (DA) average 4.0 +/- 1.5 mm (range 2 to 9 mm). Successful
      implantation was achieved in 36 procedures (94.7%). Complete closure immediately
      postimplantation was achieved in 15 (45.4%), 12 (36.3%) had trivial and 6 (18.1%)
      severe residual shunt. In four cases we implanted successfully a second device.
      At the follow-up (average 24 months) in 31 patients, 87.0% (n = 27) had complete
      closure and 96.7% (n = 30) did not need another intervention. Device embolization
      to distal left pulmonary artery occurred in two cases (5.2%), one was retrieved
      by surgery and in the other case it was allowed to remain. No mortality was
      observed. This results confirm the efficacy, with low morbidity and no mortality
      of TUC, especially in those with smaller PDA (< 4 mm).

PMID- 8561657
TI  - [Echocardiographic indicators of the surgical moment in chronic severe aortic
      insufficiency].

PMID- 8561658
TI  - [Electrophysiologic approach to the diagnosis of left ventricular hypertrophy].

PMID- 8561659
TI  - [Heart catheterization: a perspective from a horizontal posture. Lessons derived
      from a Gerzso painting].

PMID- 8561660
TI  - Heterosexual and homosexual coercion, sexual orientation and sexual roles in
      medical students.
AB  - Rape has been conceptualized on a dimension of normal male behavior. The Koss and
      Oros (1982) study used a questionnaire that allowed men to respond only as sexual
      aggressors of women, and women only as victims of men. Medical students'
      responses to a modified questionnaire, in which both sexes reported being
      aggressors and/or victims, revealed that relatively comparable proportions of men
      and women were victims of coercive experiences: 35% of women and 30% of men
      experiencing constant physical attempts to have sexual activity. Forms of
      coercion not involving threat or use of force were more common, more exclusively
      heterosexual, and carried out by more equivalent percentages of men and women.
      15% of women and 12% of men felt initially coerced into sexual activity but then
      enjoyed it. Threat or use of force to attempt to or to obtain intercourse were
      employed by 4% of men and 2% of women and experienced by 5% of both sexes. Half
      the male victims and female aggressors and a quarter of the male aggressors and
      female victims who reported such coercion stated it was homosexual. The ratio of
      homosexual/heterosexual feelings reported by male, but not female, students
      correlated with the degree of the homosexual coercion they both carried out and
      experienced. The degree of sexual coercion carried out by men and women
      correlated with their masculine sex role scores, suggesting, if the dimensional
      concept of rape is valid, that rape is on a continuum with masculine rather than
      male behaviors.

PMID- 8561661
TI  - Professional HIV risk taking, levels of victimization, and well-being in female
      prostitutes in The Netherlands.
AB  - Professional HIV risk taking (nonconsistent condom use with clients) of female
      prostitutes in The Netherlands is addressed within the context of (early)
      experiences with abuse, well-being, coping behavior, job satisfaction, and
      financial need. Data were gathered from 127 female prostitutes on condom use,
      financial need, and professional attitude, and on experiences with violence and
      abuse, physical complaints, psychosocial problems, and coping responses. Violent
      traumatic experiences were found to relate to more severe complaints and
      problems, and a higher frequency of emotion-focused coping strategies. A risk
      taking protection style (as opposed to consistent condom use and selective risk
      taking) appeared to be associated with more severe experiences with violence,
      both in childhood and in adult life, with more frequent dissociation as a coping
      behavior, and with more psychosomatic complaints. Of all the relationships found,
      more severe experiences with violence on the job were most strongly related to a
      higher professional HIV risk.

PMID- 8561662
TI  - Habituation of female sexual arousal to slides and film.
AB  - The habituation of genital and subjective sexual arousal in women was assessed.
      In a first experiment 32 women were randomly assigned to either a constant
      stimulus condition in which subjects were exposed to the same erotic slide on
      repeated trials within one session, or to a varied stimuli condition in which
      subjects were exposed to various erotic slides. A second experiment assessed
      habituation of sexual responses of 42 women to erotic film excerpts. In both
      experiments repeated erotic stimulation was followed by a novel erotic stimulus
      to study the effect of novel stimulation to a sequence of uniform stimulation. In
      the first experiment a floor effect was found in response to the first three
      trials that prevented a valid interpretation of responding on subsequent trials.
      We conclude that slides yield too little sexual arousal in female subjects. In
      the second experiment only a slight decline in genital responding was observed.
      Women sustained considerable levels of genital arousal even after 21 trials of
      uniform stimulation. Facial EMG was used as a physiological marker of emotional
      experience. Zygomatic activity decreased over trials, suggesting decreasing
      positive affect as a result of uniform stimulation. Results are discussed in the
      context of selective attention, characteristics of the habituation stimulus, and
      novelty.

PMID- 8561664
TI  - The Adolescent Sexual Interest Card Sort: test-retest reliability and concurrent
      validity in relation to phallometric assessment.
AB  - Test-retest reliability and concurrent validity studies on the Adolescent Sexual
      Interest Card Sort (ASIC) were conducted in two samples of 38 juvenile sexual
      offenders, each. Of the 64 items of the ASIC, 60 were found to be significantly
      correlated across test administrations. Cronbach's coefficient alpha was employed
      to determine the internal consistency of ASIC items. Coefficients ranged from .62
      to .96 across categories, with an overall alpha of .97. Client ratings of sexual
      interests via the Card Sort were correlated with phallometric response to similar
      categories of stimuli. Significant correlations were found for only 4 of the 14
      categories examined, suggesting little correspondence between client report of
      sexual interest on the ASIC and phallometric assessment of the same. Findings are
      consistent with the adult sex offender literature suggesting that self-report
      measures are particularly vulnerable to dissimulation and often at variance with
      more objective measurement. Clinical and research issues pertinent to the
      measurement of sexual arousal and interest in juvenile sexual offenders are
      discussed.

PMID- 8561663
TI  - Comparison of height and weight in homosexual versus nonhomosexual male gender
      dysphorics.
AB  - The authors' clinical impression that homosexual gender-dysphoric males are
      physically smaller than nonhomosexual gender-dysphoric males was tested. Subjects
      were 176 homosexual and 246 nonhomosexual male outpatients, ages 16 to 65, who
      complained of discontent with their biological sex. Compared with the
      nonhomosexual male gender dysphorics, the homosexual gender dysphorics were
      shorter, lighter, and lighter in proportion to their height. The homosexual
      gender dysphorics were also shorter than men in the general population, whereas
      the nonhomosexual gender dysphorics were not. The smaller physiques of homosexual
      gender-dysphoric men may partly explain the clinical observation that these
      patients are somewhat more successful in passing as women.

PMID- 8561665
TI  - Bias towards gay patients by psychoanalytic clinicians: an empirical
      investigation.
AB  - Results of an empirical investigation of psychoanalysts' attitudes towards and
      clinical assessment of gay patients are reported. The study employed matched
      vignette methodology; analysts rated their reactions on the Semantic Differential
      to homosexual and heterosexual patients with identical histories. They also rated
      degree of impairment in psychological functioning on the Global Assessment of
      Functioning and made DSM-III-R diagnoses. Results indicate that psychoanalysts
      maintain a subtle but significant negative bias towards homosexual patients,
      particularly those that have serious psychopathology. A negative bias towards the
      mentally ill in general also emerged. Suggestions for future studies and
      implications for training clinicians are discussed.

PMID- 8561666
TI  - Ritual female genital surgery among Bedouin in Israel.
AB  - Ritual female genital operations are common in many parts of the world, with
      varying degrees of mutilation from clitoridectomy and removal of the labia to
      removal of the clitoral prepuce. Interviews of 21 Bedouin women in southern
      Israel revealed the practice to be normative in several tribes. However, physical
      examination of 37 young women from those tribes at a gynecological clinic
      revealed only small scars on the labia in each woman. Bedouin in southern Israel
      may offer a model of evolution of female circumcision into a nonmutilative ritual
      incision.

PMID- 8561667
TI  - [Smoking and health].

PMID- 8561668
TI  - [Percutaneous transluminal coronary angioplasty and myocardial revascularization.
      Current status and role of clinical trials].

PMID- 8561669
TI  - [Hemodynamic impact of thrombolytic therapy in acute pulmonary thromboembolism].
AB  - PURPOSE: To evaluate pre and post-hemodynamic changes after thrombolytic therapy
      in patients with acute pulmonary embolism with multiple pulmonary segments
      compromised. METHODS: Nine patients, 5 females, aged between 27 and 83 (mean 62
      +/- 16) years, with the onset of symptoms preceding 7 days, were submitted to
      thrombolytic therapy, administered after baseline perfusion-ventilation lung
      scan, echodopplercardiography (ECO) and hemodynamic measurements with a Swan-Ganz
      thermodilution catheter. The same procedures were done after the thrombolytic
      infusion. Streptokinase (SK) was used in 7 (78%) cases and recombinant human
      tissue-type plasminogen activator (rt-PA, alteplase) in 2 with the following
      doses: SK-250,000 i.u. infusion over 30 min, then 100,000 i.v/h over 24 to 72 h
      and rt-PA-20 mg in bolus infusion, then 80 mg over 6 h. Thrombolytic was infused
      in pulmonary artery trunk in 8 (88%) cases and a peripheral vein in 1 (12%) case,
      until mean pulmonary artery pressure (PAP) reached 20 mmHg. All patients received
      i.v. heparin and oral anticoagulation after thrombolytic therapy. RESULTS: A
      significant (p < 0.05) decrease in right atrial pressure (12 +/- 3 vs 8 +/- 2
      mmHg), PAP (32 +/- 5 vs 19 +/- 2 mmHg), pulmonary vascular resistance (397 +/-
      125 vs 87 +/- 24 dyne.s/cm5) and increase in cardiac output (3.4 +/- 0.5 vs 5.5
      +/- 1.0 l/min) and stroke volume (30 +/- 5 vs 57 +/- 10 ml/beat) were observed
      after thrombolytic infusion. Two patients died as a result of pulmonary infection
      unrelated to the embolic event or thrombolysis. Minor bleeding complications
      occurred in two cases and major in one patient with orthopedic prosthesis.
      CONCLUSION: Thrombolytic therapy exert desirable effects on hemodynamic
      abnormalities, achieving lungs scan and ECO improvement in patients with acute
      pulmonary embolism.

PMID- 8561670
TI  - [Assessment of the Bezold-Jarisch reflex in experimental myocardial infarction].
AB  - PURPOSE: To evaluate the cardiogenic depressor Bezold-Jarisch reflex in rats with
      chronic myocardial infarction. METHODS: Adult Wistar rats were submitted to
      ligation of the anterior descending coronary artery of the left ventricle (group
      INF, n = 15) and compared with rats submitted to sham-operation (group Sham, n =
      15). Thirty days after the surgery, without influence of anesthetics, the basal
      mean arterial pressure (MAP) and heart rate (HR) were measured. Immediately
      after, the Bezold-Jarisch reflex was evaluated measuring the falls in diastolic
      arterial pressure (DAP) and the simultaneous bradycardia induced by injections of
      5-hydroxytryptamine (5-HT, 4 to 32 micrograms/kg, i.v.). RESULTS: The INF group
      showed significantly lower basal MAP and HR values (103 +/- 3 mmHg and 328 +/- 6
      bpm) when compared to the Sham group (110 +/- 2 mmHg and 348 +/- 7 bpm). The
      Bezold-Jarisch reflex was significantly attenuated in the INF group (falls of DAP
      from 2 +/- 2 to 31 +/- 3 mmHg and HR from 8 +/- 5 to 204 +/- 15 bpm), when
      compared to the Sham group (falls of DAP from 10 +/- 3 to 41 +/- 3 mmHg and HR
      from 58 +/- 12 to 276 +/- 16 bpm). The morphological analysis showed a myocardial
      infarction mainly located at the anterolateral portion of the left ventricle with
      a maximal extension of 35% of the left ventricle circumference. The INF group
      showed right ventricular and left atrial hypertrophy when compared to the Sham
      group. CONCLUSION: The experimental chronic myocardial infarction in rats is
      followed by significant attenuation of the Bezold-Jarisch reflex, probably as
      result of a heart failure and, consequently, of functional alterations in the
      chemosensitive receptors of cardiac unmyelinated vagal afferents.

PMID- 8561671
TI  - [Antiarrhythmic drug effectiveness. Proposal for a new approach based on
      pharmacological hourly effects].
AB  - PURPOSE: To use a new approach in order to assess the antiarrhythmic drugs, based
      in the hourly autonomic effects and antiarrhythmic efficacy of sotalol. METHODS:
      Sixteen patients were evaluated in a randomized double-blind placebo-controlled
      study. Patients were classified in group 1 (anti-arrhythmic efficacy) and group 2
      (no antiarrhythmic efficacy). The following parameters were analyzed: 1) clinical
      variables as age, gender, cardiac disease and ventricular ectopies density; 2)
      drug effects on pNN50 in 24-hour and on mean hourly cardiac cycle length; 3)
      percentage of hourly ventricular ectopies distribution and its correlation with
      pNN50 and with mean hourly cardiac cycle length in all patients; 4) drug effects
      on mean hourly cardiac cycle length in groups 1 and 2; 5) correlation between
      hourly pNN50 and ventricular ectopies density after sotalol administration in
      groups 1 and 2; 6) hourly drug efficacy in groups 1 and 2 and correlation with
      pNN50. RESULTS: Efficacy of the drug was present in 8 (50%) patients. Sotalol
      significantly increased 24-hour pNN50 (placebo 5.01 +/- 2.02%; after drug, 11.70
      +/- 5.59%-p < 0.001), also increasing mean hourly cardiac cycle length during the
      day and night, in all patients (placebo 758.25 +/- 75.68 ms; after drug 967.71 +/
      80.17 ms-p < 0.000). It was noted that patients under placebo had different
      autonomic tonus; group 1 showed higher sympathetic activity as compared to group
      2. Hourly drug efficacy was seen in 23 of 24-hour recordings in group 1 while it
      was not seen at any time in group 2. CONCLUSION: Sotalol significantly increased
      parasympathetic cardiac activity. The anti-arrhythmic response was related to the
      autonomic tonus seen before and after drug administration.

PMID- 8561672
TI  - [Relationship between ventricular arrhythmia and cardiac function in Chagas
      disease].
AB  - PURPOSE: It is well established the association between heart failure and
      arrhythmias in different cardiopathies. There are no studies in Chagas'
      myocardiopathy that analyze the relation between arrhythmias and left ventricular
      function. METHODS: We studied 629 patients with Chagas' disease, divided in 3
      groups, according to ejection fraction obtained through echocardiographic study
      (normal, between 0.64 and 0.45, and below 0.44). RESULTS: At conventional ECG,
      the presence of ventricular arrhythmias was respectively in the 3 groups: 15%,
      36% and 64%, showing higher incidence when left ventricular function was getting
      worse. CONCLUSION: Ventricular arrhythmias in Chagas' disease are frequent in
      patients with normal ejection fraction, and become more intense as ventricular
      dysfunction progresses.

PMID- 8561673
TI  - [Infections in 100 heart transplantation patients].
AB  - PURPOSE: A prospective study of infective agents in diagnosed infections and
      deaths by specific agents in cardiac transplant patients. METHODS: Infections
      occurring in a series of 100 consecutive cardiac transplant patients after
      transplantation with definite infectious diagnosis were studied; follow-up after
      transplantation was 3 to 90 (medium 25.38 +/- 25.97) months. Diagnostic criteria
      for defining infections were those used in the Epidemiology and Quality Control
      Division of the INCOR, that are the same published by the Centers for Disease
      Control. The following parameters were analysed: infections/patient/time, causes
      of infection and organs infected, clinical presentation and clinical aspects of
      infections, methods used for the infective diagnosis and relationship between
      rejection episodes and infection. Death caused by infections and survival rates
      per infection were also studied. RESULTS: Bacterial infections were more frequent
      (56.3% of all infections), followed by viral infections (19.6%), fungal
      infections (18%) and protozoal infections (6.1%). Of all deaths after
      transplantation, 25% were caused by infections. CONCLUSION: Infections are an
      important cause of mortality and morbidity in this patient population; our data
      are in accordance to the other reported series.

PMID- 8561674
TI  - [Heterotopic heart transplantation. Initial clinical experience].
AB  - PURPOSE: To report our initial clinical experience with heterotopic heart
      transplantation, stressing its indications and a new modification in surgical
      technique. METHODS: We studied three patients underwent heterotopic heart
      transplantation, using an original technique in one of them. This new technique
      allows to connect both pulmonary arteries without any prosthetic tube. RESULTS:
      One early death and two late survivors, with 17 and 20 months of follow-up. One
      of them is clinically well and practices sports, regularly. CONCLUSION:
      Heterotopic heart transplantation could be considered as a good therapeutic
      option for end-stage patients with cardiomyopathy and right pulmonary vascular
      resistance, specially those with right ventricle. It can improve general results
      of heart transplantation because it reduces the early risks related to
      hemodynamic problems in a selected group of patients.

PMID- 8561675
TI  - [Adequacy of of pacemakers responsive to the volume-minute ventilation rate in
      heart transplantation patients].
AB  - PURPOSE: To evaluate in the late post-operative period (PO) the chronotropic
      response to exercise of patients submitted to orthotopic cardiac transplantation
      (CT) and the implant of a cardiac pacemaker (PM). METHODS: A rate response
      ventricular PM (VVI+R) which uses minute ventilation (MV) as a sensor was
      implanted in five patients in the early PO of CT due to chronotropic
      incompetence. The patients were 31 to 64 years old and the indication to implant
      of PM was low ventricular escape rhythm following atrial taquicardia/bradycardia
      (one case) or sinus bradycardia (4 cases). The study was performed by means of
      paired exercise tests using Naughton protocol in order to compare the heart rate
      in VVI (prefixed heart rate) and VVIR+MV (rate response) mode. The duration of
      the exercise was compared between the two modes of stimulation. RESULTS: In VVI
      mode the heart rate was significantly lower than in VVIR+MV mode for comparable
      periods of exercise (101 +/- 12 ppm vs 132 +/- 4 ppm; p < 0.05); in VVIR+MV mode
      the patients had a prolonged time of exercise as compared to VVI mode (15 +/- 7
      min vs 12 +/- 7 min; NS). CONCLUSION: The MV rate response PM provided patients
      with satisfactory heart during exercise and may be an adequate option to patients
      submitted to CT who present chronotropic incompetence.

PMID- 8561676
TI  - [Prevalence study of hypertension among students at the Medical Science
      Department of the University of Taubate].
AB  - PURPOSE: To study the prevalence of hypertension related on the exposition to the
      main risk factors. METHODS: We studied 153 students of the Medical Science
      Department of Taubate University, aged between 17 to 35 years. The chosen method
      was the stratified simple aleatory sample. RESULTS: The prevalence of
      hypertension was 5.88% where all of them had one or more risk factor. A
      significant systolic blood pressure increase in male was found by comparing to
      the female. CONCLUSION: The risk factors considered alone, did not change the
      mean value of the hypertension, while the obesity when associated with one or
      more risk factors showed a considerable increase on the averages of diastolic
      blood pressure.

PMID- 8561677
TI  - [Coronary artery dissection without acute myocardial infarction].
AB  - A 57 year-old-man with acute aortic dissection (DeBakey type I) who developed
      right coronary artery dissection without acute myocardial infarction. He was
      successful surgically treated and became asymptomatic.

PMID- 8561678
TI  - [Interstitial collagen matrix and its relationship with expansion of acute
      myocardial infarction].

PMID- 8561679
TI  - [Obesity and hypertension].

PMID- 8561680
TI  - [Efficacy and tolerability of the captopril and hydrochlorothiazide combination
      in the treatment of mild to moderate hypertension. Multicenter study].
AB  - PURPOSE: To evaluate the antihypertensive efficacy and tolerability of captopril
      50 mg + hydrochlorothiazide 25 mg daily in mild to moderate primary hypertension.
      METHODS: Out-patients (n = 471) with mild to moderate hypertension, diastolic
      blood pressure (DBP) 95-115 mmHg, with 15 days of washout, were included to the
      treatment initially with half tablet of the association of captopril 50 mg +
      hydrochlorothiazide 25 mg once daily, for 30 days. After this period, patients
      with DBP > 90 mmHg had the dosage duplicated, while the others had the same
      dosage for 60 days more. Evaluation was performed 15 days before and then every
      month during active drug. RESULTS: Twenty six patients were withdrawn, 13 (2.7%)
      by adverse effects and 13 by protocol violation. At the end of the wash-out
      period, the blood pressure (BP), 162 +/- 16/103 +/- 6 mmHg decreased
      significantly at the 30th day to 146 +/- 14/92 +/- 8 mmHg (p < 0.001 vs 0th day);
      139 +/- 12/86 +/- 7 mmHg at the 60th day, (p < 0.001 vs 30th day), and further to
      136 +/- 11/84 +/- 5 mmHg, (p < 0.001 vs day 0) till the end of the 90th day.
      Antihypertensive efficacy (DBP < or = 90 mmHg and decreased of the DBP > or = 10
      mmHg) was obtained in 82% of the patients. There was no difference in BP control
      considering race, hypertension level, previous antihypertensive treatment and
      obesity. Cough (4%) was the main adverse event. CONCLUSION: Captopril +
      hydrochlorothiazide was effective and safe in the treatment of mild to moderate
      hypertension. The favorable response was observed in 82% of the patients
      independently of race, hypertensive level, previous antihypertensive treatment
      and obesity. Low incidence of side effects was reported, with no difference from
      others reported in the literature.

PMID- 8561681
TI  - [Changes in the treatment of pulmonary embolism].

PMID- 8561682
TI  - [Recommendations of the Department of Arrhythmia and Clinical Electrophysiology
      (DAEC) of the Brazilian Cardiology Society on indications for permanent pacemaker
      implantation, choice of stimulation mode, and indications for automatic
      cardioverter-defibrillator implantation].

PMID- 8561683
TI  - [Electrophysiological study and cardiac arrhythmia ablation using
      radiofrequency].

PMID- 8561684
TI  - Cochlear implants in China.
AB  - China has approximately 6 million totally deaf people according to an official
      survey conducted in 1990, although the actual number is probably higher. A
      primary cause of deafness is the use of ototoxic drugs. There does not appear to
      be any emergent deaf culture in China at present. As the only available medical
      device that can restore partial hearing to a totally deaf person, the cochlear
      implant has been in development in China since 1979. This paper provides an
      overview of cochlear implants in China and is based on a review of published
      materials, visits to research institutes and hospitals, and personal
      communication with Chinese colleagues. As of 1993, about 1,000 deaf people,
      including 50 children below age 12 years, have received four types of single
      electrode cochlear implants that were developed and fabricated by institutions in
      China. These single-electrode devices have provided an aid to lip reading, but
      are no longer in use due to their inability to produce open-set speech
      recognition. Present implant research in China focuses on development of multi
      electrode devices. Basic research in electrical stimulation is relatively lacking
      and standardized audiological evaluation for cochlear implant effectiveness needs
      to be developed. The present economic growth and legal system reform in China,
      combined with advances in implant technology, may make it possible to produce an
      affordable yet effective cochlear implant system. This paper discusses cochlear
      implants only in China, but the social and economic factors are similar in many
      developing countries in Asia, South America, Eastern Europe, and Africa, where a
      low-cost, high-performance cochlear implant system is also needed.

PMID- 8561685
TI  - Dispositional optimism, dysphoria, health, and coping with hearing impairment in
      elderly adults.
AB  - Sixty-eight elderly hearing impaired subjects were interviewed and completed self
      report measures on hearing disability, dispositional optimism, dysphoria, and
      general health. The measures used were the Hearing Coping Assessment (HCA), the
      Hearing Questions (HQ), the Life Orientation Test (LOT), The Beck Depression
      Inventory (BDI), and a subscale from the Goteborg Quality of Life (GQL).
      Psychometric analyses of HCA, HQ, LOT, BDI, and GQL revealed high reliability in
      terms of Cronbach's Alpha and split-half r's. Significant intercorrelations were
      found between several measures, but not with pure-tone audiometry (0.5, 1, 2, and
      3 kHz). Cluster analysis was used to identify subgroups in the sample. As a
      result three clusters were identified interpreted as 'high copers', 'copers with
      moderate psychological and somatic complaints', and 'low copers'. Results from
      the cluster analyses were confirmed by using two different clustering methods and
      by between-cluster comparisons on the HQ, which had not been used to obtain the
      clusters.

PMID- 8561686
TI  - Test-retest reliability of a dichotic digits test for assessing central auditory
      function in Alzheimer's disease.
AB  - Test-retest reliability for the dichotic digits test was measured in 10 subjects
      diagnosed with mild-to-moderate Alzheimer's disease and a control group of 10
      subjects with no evidence of dementia, matched for age, gender and average degree
      of hearing loss. Although initial scores among the Alzheimer group were more
      variable, test-retest reliability over a month period was reasonably high for
      both subject groups. Results are in agreement with previous reports on dichotic
      digits showing good sensitivity, ease in administration and time efficiency. Use
      of the dichotic digits test for screening of central auditory function in the
      Alzheimer population is supported.

PMID- 8561687
TI  - Application of the Audioscan in the detection of carriers of genetic hearing
      loss.
AB  - The authors describe the establishment of normative stimulus parameters for the
      Audioscan, an automated sweep frequency audiometer, for its application in the
      detection of audiometric notches in carriers of recessive genetic hearing loss. A
      sweep rate of 30 s/octave over the frequency range 300 to 4000 Hz pulsing at 2.5
      pulses/s at -5 dB with a step size of 5 dB were ultimately adopted. The criterion
      for notches was 15 dB or greater within the frequency range 500-3000 Hz. Adopting
      this criterion, 14.2% of control subjects had notches. Among parents of children
      with non-syndromal recessive hearing loss 55% were found to have notches. Notches
      were found more frequently among mothers and sisters than among fathers and
      brothers of the patients.

PMID- 8561688
TI  - Interferon-induced sudden hearing loss.
AB  - With the increasing long-term use of interferon (IFN), several new adverse
      effects have been recognized. Very little attention, however, has been paid to
      auditory acuity. We encountered 3 cases of sudden hearing loss associated with
      IFN. We then conducted a prospective study to assess the auditory function of 73
      patients receiving IFN. Auditory disability (tinnitus and/or hearing loss)
      occurred in 32 patients (43.8%) during IFN therapy, among which audiometry
      documented sensorineural hearing loss in 27 cases (36.9%); 17 (48.6%) of the 35
      patients receiving IFN-beta had auditory disability, including hearing loss in 13
      cases (37.1%), and 15 (39.5%) of 38 patients receiving IFN-alpha suffered from
      auditory disability. There was not much difference between the influences of IFN
      alpha and -beta. Auditory disability frequently developed in the later stages of
      treatment, and most patients recovered 7-14 days after the discontinuation of
      IFN. The results demonstrate that sudden hearing loss can occur as a side effect
      of treatment with IFN. This may reveal the association between autoimmunity and
      sudden hearing loss.

PMID- 8561689
TI  - Binaural hearing in adults with histories of otitis media in childhood.
AB  - There is evidence that children with recent histories of otitis media (OM) have
      poorer binaural hearing than children with no such histories. In order to
      investigate whether these deficits persist into adulthood, young adults were
      selected for auditory testing on the basis of responses to a questionnaire on
      childhood OM. Binaural performance measures were obtained for the binaural
      masking level difference, binaural loudness summation and lateralisation of
      binaural clicks. Although subjects with OM histories reported more auditory
      disabilities in adulthood, there were no significant differences in binaural
      performance between OM history subjects and controls. It is suggested that
      binaural deficits resulting from OM do not usually persist into adulthood.

PMID- 8561690
TI  - Evaluation of self-report by adults of childhood otitis media histories.
AB  - Several studies have suggested that reported auditory disabilities in adults are
      associated with reported histories of otitis media (OM) in childhood. However, no
      evaluation has previously been made of the accuracy of recall of childhood OM by
      adult subjects. In an investigation in university students, questionnaire
      responses on childhood OM histories were evaluated for 31 subjects reporting no
      known OM histories. Responses were compared with information obtained from GP
      (Family Doctor) records and parents. Agreement was very good for questions on ENT
      surgery, reasonably good for attendances at ENT clinics and poorer for GP
      attendances. It was concluded that the questionnaire approach was sufficiently
      valid in obtaining information from adults about childhood OM histories.

PMID- 8561691
TI  - Performance of adult Ineraid and Nucleus cochlear implant patients after 3.5
      years of use.
AB  - Forty-two postlingually deafened adult patients, 21 with a formant extraction
      version of the Nucleus cochlear implant and 21 with the Ineraid cochlear implant
      (analog processing), were evaluated on a series of speech perception tests after
      using their implants for about 3.5 years. A wide range of performance was
      observed across patients for both devices. All but 4 patients showed an
      enhancement in their lipreading ability with the implant. Word recognition
      averaged about 14-19% correct, and word recognition in sentences averaged about
      43-49% correct for the two implant groups. Average performance was superior with
      the Ineraid implant on consonant recognition in noise. An information
      transmission analysis suggested that vowel perception was influenced by first-
      and third-formant frequency for the Nucleus, and first-formant and fundamental
      frequency for the Ineraid patients. It appeared that the Ineraid device was more
      effective, on average, at conveying information about consonant nasality and
      frication. For consonant perception, nasality and frication contributed most to
      the total information transmitted for both implant types. Both devices had
      difficulty conveying information about vowel second-formant frequency and
      consonant place information. These scores at 3.5 years are substantially elevated
      from preoperative performance and, overall, the patients clearly benefit from
      their implant.

PMID- 8561692
TI  - Multicentric field evaluation of a new speech coding strategy for cochlear
      implants.
AB  - In a multicentric study involving 4 European cochlear implant centers, the speech
      perception abilities of 20 native German-speaking individuals implanted with the
      Nucleus 22 Channel Cochlear Implant System when using a new spectral peak (SPEAK)
      speech coding strategy were investigated. This strategy continuously analyzes the
      speech signal using 20 digital programmable bandpass filters and presents up to
      10 spectral maxima to the 22 implanted electrodes. Each subject's performance on
      a variety of auditory perceptual tasks was evaluated with the experimental
      encoder (SPEAK), relative to his or her performance in a reference condition. An
      ABAB experimental design was used whereby each strategy was reversed and
      replicated. The reference levels of auditory performance were established using
      the multipeak (MPEAK) speech-processing strategy of the Nucleus speech processor.
      Only subjects who achieved open-set monosyllable word recognition in the
      reference condition were included in this study. Significant differences in group
      mean scores for most speech recognition subtests were obtained for the SPEAK
      versus the MPEAK strategy. The largest overall improvements were observed for the
      sentence tests under noisy conditions.

PMID- 8561693
TI  - Re: Cobb FE: Age-associated degeneration of backward masking task performance:
      evidence of declining temporal resolution abilities in normal listeners.

PMID- 8561694
TI  - Topography of binaural interaction in the auditory brainstem response.
AB  - The scalp topography of binaural interaction (BI) in the auditory brainstem
      response (ABR) was studied in fourteen normal individuals. BI was observed from
      all recording sites of the scalp, and the peak amplitude was noted mostly in the
      bilateral parietal and occipital regions. There was a significant difference in
      amplitude shown by significance probability mapping (SPM) when the waveform
      obtained by binaural stimulation was compared with the sum of the waves obtained
      by monaural stimulation. The topography of BI was different from that of the wave
      III and the wave IV/V complex. In contrast to previous reports by other workers,
      we found that BI mainly corresponded to the first half of the wave IV/V complex.

PMID- 8561695
TI  - Relationship between head sway and center of foot pressure sway.
AB  - We investigated the correlation between body sway and head sway in 64 healthy
      subjects who stood on a force-measuring platform. Each subject wore a helmet
      attached to a cephalograph and was asked to stand as still as possible on a
      platform with his feet close together for 60 sec. Subjects were asked to do this
      three times with their eyes closed and three times with their eyes open. We
      selected the test with the minimum sway for computer analysis of the sway path,
      sway area, ratio of anteroposterior/lateral components, sway velocity in each
      direction, averaged divisional frequency, and Romberg quotient. The movement of
      the head was significantly correlated with the center of foot pressure (COF) for
      the sway path, sway area, sway velocity, averaged divisional frequency, and the
      Romberg quotient. Our findings suggest that COF sway can be used instead of head
      sway to assess those five parameters.

PMID- 8561696
TI  - Detection of specific IgE antibodies to Japanese cypress pollen in patients with
      nasal allergy: a comparative study with Japanese cedar.
AB  - Japanese cypress pollinosis has recently attracted attention and its clinical
      relationship with Japanese cedar pollinosis has been pointed out. To compare the
      two kinds of pollinosis, we retrospectively examined specific IgE antibodies to
      both pollen of Japanese cypress and cedar in the sera of 150 patients with nasal
      allergy using AlaSTAT assay. During the season in which the pollens of these two
      species are dispersed, the positive rates for Japanese cypress and cedar
      increased to 51.4 and 75.0%, respectively. The percentage of patients positive
      for both of cypress and cedar was elevated to 51.4%, corresponding to 68.5% of
      the total patient group positive for cedar. Almost all the cases positive for
      cypress had IgE antibodies to cedar, the value of which was considerably higher
      than that of cases positive only for cedar. Furthermore, increases in titers of
      specific IgE antibodies to cypress was observed in four of six cases, compared
      between specific IgE antibodies to cypress in pre- and post-dispersion of cypress
      pollen. These findings suggest the following possibility: (i) there is cross
      antigenicity between the two pollen species, and (ii) patients are
      immunologically affected by cypress pollen to express higher levels of specific
      IgE antibodies after pollen dispersion.

PMID- 8561697
TI  - Eosinophil cationic protein in perennial allergic rhinitis.
AB  - For a quantitative investigation of eosinophil activation in perennial allergic
      rhinitis, eosinophil cationic protein (ECP) concentrations were measured by a
      radioimmunoassay in serum, nasal secretions (ECPWN) and in the supernatant of
      these nasal secretions (ECPsup) obtained from normal subjects and allergic
      patients. Levels of ECPWN and ECPsup were higher than that of ECPserum. ECPsup
      showed a positive correlation with clinical severity, despite the lack of a
      significant correlation with eosinophilia in nasal smears. ECPWN and ECPserum
      showed no significant correlation with any of these clinical parameters. There
      was a weak tendency toward an increase in histamine sensitivity of the nasal
      mucosa of allergic patients with higher ECPsup although this was not
      statistically significant. These results suggest accumulation and activation of
      eosinophils in the allergic nasal mucosa, and also indicate that ECPsup may be a
      clinical parameter of perennial allergic rhinitis.

PMID- 8561698
TI  - Clinical assessment of squamous cell carcinoma of the nasal cavity proper.
AB  - The subjects were 14 patients with squamous cell carcinoma or undifferentiated
      carcinoma of the nasal cavity treated at Nihon University Hospital between
      October 1984 and November 1991, who were followed for at least 3 years. The site
      of the tumor origin within the nasal cavity was the lateral wall in 8 patients,
      the nasal septum in three patients, and unknown in three patients.
      Histologically, there were 13 squamous cell carcinomas in (3 well differentiated,
      7 moderately differentiated, and 3 poorly differentiated) and 1 undifferentiated
      carcinoma. Treatment was by a combination of radiotherapy, chemotherapy, and
      surgery in 8 cases, a combination of radiotherapy and surgery in 5 cases, and
      surgery alone in 1 case. The 3-year and 5-year Kaplan-Meier survival rates were
      86 and 69%, respectively. A total of 6 patients suffered a recurrence, with local
      recurrence occurring in 4 patients and pulmonary metastasis in 2 patients. Tumor
      control was achieved in 3 of the 4 cases of local recurrence by reoperation, and
      by surgery in 1 of the 2 cases of pulmonary metastasis. The duration of the
      recurrence-free interval in the patients who developed local recurrences, 18 to
      46 months after the completion of the initial course of therapy, was of
      considerable interest.

PMID- 8561699
TI  - Effects of oxygen radicals on ciliary motility in cultured human respiratory
      epithelial cells.
AB  - There are few reports about direct effects of specific oxygen products on ciliary
      function because of their instability and reactivity. We investigated the direct
      effects of superoxide anion (O2-) and of hydrogen peroxide (H2O2) on the ciliary
      function of human respiratory epithelial cells, using monolayer cell cultures,
      high speed video analysis of frequency (CBF), amplitude (CBA), and coordination
      of ciliary beats and evaluating the surface structural changes of ciliated cells
      at the same time. 10(-2) M H2O2 decreased ciliary beat activity. The CBF was 36.5
      +/- 4.4% and the CBA was 51.0 +/- 3.8% of the baseline (time = 0) after 5 min
      (all p < 0.001). Catalase (2 micrograms/ml) abolished the ciliotoxic effect of
      H2O2. The O2- produced by reaction of xanthine (0.06 mM)-xanthine oxidase (0.04
      U/ml) caused a temporary rapid increase of 26.8 +/- 1.7% in CBF and an increase
      of 42.5 +/- 4.1% in CBA after 15 sec (all p < 0.001). Superoxide dismutase
      significantly reduced these increases. Results indicated that O2- activated
      ciliary function with a temporary increase in O2(-)-production. This suggests
      that the removal of H2O2 from the O2- reaction is important in improving
      mucociliary clearance in excessive oxygen metabolites.

PMID- 8561700
TI  - On the frequency of thyroid diseases in outpatients in an ENT clinic.
AB  - The prevalence of thyroid diseases was studied in the ENT department of Kobe
      Teishin Hospital. Between January 1990 and June 1994, 6,348 outpatients (3,004
      women and 3,344 men) visited the ENT department with problems of ear, nose, and
      throat. Among them 114 patients (82 women and 32 men) were revealed to have
      thyroid diseases (1.8%). The prevalence of thyroid diseases increased in patients
      over the age of 40 (4.6% for 40-80 year aged women, 1.6% for 40-80 year aged
      men). The male/female ratio was about 1:2.7. There was no subjective symptom in
      86.8% of the patients. The prevalence of Hashimoto's thyroiditis was 53.5%,
      nontoxic diffuse goiter 16.7%, cyst(s) 8.8%, adenoma 7.0%, nontoxic nodular
      goiter 4.4%, subacute thyroiditis or acute exacerbation of Hashimoto's
      thyroiditis 4.4%, Graves' disease 1.8%, thyroid carcinoma 1.8%, adenomatous
      goiter 0.8%, and primary hypothyroidism 0.8%. Visible goiter was observed in only
      5 patients and 93% of the patients had palpable but not visible thyroids.
      Therefore, it is important to palpate the thyroid gland during examination of the
      neck not only in women but also in men. Hashimoto's thyroiditis is thought to be
      increasing in frequency and is becoming a more important disease in the ENT
      clinic.

PMID- 8561701
TI  - A case of acquired petrous cholesteatoma associated with insidious middle ear
      infection treated by staging the surgical procedures.
AB  - Surgical treatment of petrous cholesteatoma is difficult, especially in infected
      cases, since it often involves vital structures. We report the case of a patient
      successfully treated for an infected petrous cholesteatoma by staging the
      surgical procedures to reduce the risk of intracranial complications. The
      patient, a 53-year-old man, was referred to our hospital because of vertigo
      during coughing or strenuous effort. The left side mastoid cavity was open to the
      external ear canal and wholly covered with cholesteatoma epithelium with purulent
      discharge. The superior basal turn of the cochlea, superior and posterior
      semicircular canals, and roof of the internal auditory canal were eroded.
      Conservative treatment was not effective in eradicating the otorrhea. Four weeks
      after the first operation (radical mastoidectomy), the second operation was
      conducted following a combined middle cranial fossa and transmastoid approach.
      The postoperative course was uneventful. Normal facial nerve function was
      preserved and unsteadiness disappeared, but hearing could not be preserved. The
      MRI examination, performed one year after surgery, did not reveal any evidence of
      residual cholesteatoma.

PMID- 8561702
TI  - A case of allergic aspergillus sinusitis with acute onset.
AB  - Reports of allergic aspergillus sinusitis have increased in recent years and
      diagnostic criteria have also come to be established, yet this disease remains a
      rare disorder. The disorder is generally reported to follow a chronic course.
      Here we report a case of allergic aspergillus sinusitis with a short morbid term
      of 3 weeks.

PMID- 8561703
TI  - Tracheo-esophageal shunt speech: report of an unusual case.
AB  - A rare case of laryngectomee who acquired TE shunt speech is reported. Our
      patient was a 64-year-old woman with laryngeal cancer (glottic type T3N0M0). She
      underwent laryngectomy in 1990, and a Komorn tracheo-esophageal shunt operation
      was performed simultaneously. A voice prosthesis (BIVONA) was inserted into the
      shunt, but the voice valve was not used. She acquired shunt speech soon after the
      operation, and there was no need to close the tracheostoma during phonation.
      Fiberoptic, X-ray and aerodynamic findings of the shunt and esophagus were as
      follows: (i) The one-way valve of the voice prosthesis was open during
      inspiration and closed during phonation. (ii) Swallowing of air, as seen in
      esophageal speech, was not observed. (iii) The neoglottis was in the upper part
      of the esophagus. It was concluded that the air for the vibration of the
      neoglottis entered the esophagus through the T-E shunt during inspiration.

PMID- 8561704
TI  - Massive subcutaneous emphysema, pneumomediastinum, and spinal epidural emphysema
      as complications of violent coughing: a case report.
AB  - A 28-year-old man who manifested subcutaneous emphysema extending from the skull
      base and face to the chest, mediastinum and spinal epidural space following
      severe coughing caused by acute bronchitis is reported. Subcutaneous emphysema is
      a manifestation of non-surgical intrathoracic pathophysiology. In this patient
      percutaneous diagnostic peritoneal lavage resulted in the release of a large
      quantity of air and was negative for bleeding or contamination. No treatment
      other than antibiotics was prescribed. In this report, computer tomography study
      successfully demonstrated the areas of massive subcutaneous emphysema and the
      disappearance of the entrapped air, that might be absorbed into the tissues in
      the occupied sites within 7 days, except the air of epidural space, of a patient
      who manifested as a consequence of severe coughing caused by acute bronchitis.

PMID- 8561705
TI  - Second malignancies developing after treatment for paediatric cancers.

PMID- 8561706
TI  - Radiology in Rwanda.
AB  - This account documents some aspects of military radiology in the aftermath of the
      Rwandan Civil War of 1994. Following the genocidal conflict of April-July 1994,
      all radiographic services ceased in Rwanda, a nation of some 7,500,000 people. As
      part of the United Nations Peacekeeping Force, UNAMIR II, the Australian Medical
      Support Force established and provided, on an ongoing basis, sophisticated
      medical, surgical and intensivist care for the sick and wounded United Nations
      personnel, of whom there were up to 7000 deployed in Rwanda; and, as part of its
      humanitarian outreach, emergency medical and surgical care for Rwandese
      civilians. The Australian contingent of 308 service personnel established the
      Australian Military Hospital (the 'United Nations Hospital') in the former Clinic
      Wing of the Kigali Central Hospital. From August 1994 the Radiology Department of
      the Australian Medical Support Force provided the first specialist X-ray services
      as part of the re-building of the stricken nation and, over the ensuing year,
      provided a diagnostic service for soldiers and civilians with both chronic and
      recent war wounds, trauma victims in the aftermath of the Civil War, sick and
      injured soldiers and Rwandese suffering from any of the full range of medical
      conditions encountered in tropical Africa.

PMID- 8561707
TI  - The role of colour and duplex Doppler ultrasound in the assessment of thyroid
      nodules.
AB  - The role of colour and duplex Doppler ultrasound in investigating nodular thyroid
      disease was evaluated. Fifty patients with solitary or dominant nodules were
      studied. All nodules were examined with colour Doppler with spectral analysis
      performed on vascular lesions. Pathological correlation was available for all
      nodules. The majority of thyroid nodules could be accurately categorized by their
      colour Doppler appearances. This was true for both solitary and dominant nodules.
      All neoplastic nodules (adenomas, carcinomas) contained intra-nodular flow
      signals. The majority of the colloid nodules were either avascular or had halo
      flow signals only. A minority of colloid nodules were vascular. These nodules
      were large (> 2 cm), had dominant halo vessels and cytological evidence of
      follicular cell hyperplasia. Although colour Doppler lacks absolute specificity
      in discriminating neoplastic and non-neoplastic thyroid nodules, the data
      suggests the modality has considerable use in clinical practice. The spectral
      analysis data was time-consuming to obtain and had less obvious clinical
      application.

PMID- 8561708
TI  - Magnetic resonance angiography findings in the early post-carotid endarterectomy
      period.
AB  - This preliminary study was designed to investigate the ability of multiple axial
      volume three-dimensional fourier transform (3DFT) time-of-flight (TOF) magnetic
      resonance angiography (MRA) to depict the carotid bifurcation in the early post
      carotid endarterectomy period. Five patients underwent intra-operative digital
      subtraction angiography (DSA) and carotid MRA within 5 days of carotid
      endarterectomy. An axial volume fast imaging in steady-state precession (FISP)
      gradient-echo 3DFT TOF carotid MRA technique in this limited series appeared to
      display accurately the surgically significant abnormalities at the carotid
      bifurcation after endarterectomy. However, in normal or near-normal intra
      operative DSA studies, overestimation of internal carotid artery stenoses was
      encountered. Postoperative MRA demonstrates potential as a useful non-invasive
      investigation after carotid endarterectomy but should be interpreted with caution
      until larger studies become available.

PMID- 8561709
TI  - A home-made phantom for learning ultrasound-guided invasive techniques.
AB  - An ultrasound phantom is described which allows practice of ultrasound-guidance
      of needle placement over variable depths and into targets of variable size. The
      phantom mimics a solid organ in its echogenicity and can be cheaply and easily
      made from resources of the domestic kitchen.

PMID- 8561710
TI  - Chaotic phasic pattern as sole ultrasound evidence of extensive post-thrombotic
      change.
AB  - We report three cases of extensive post-thrombotic change confirmed at ascending
      venography but which did not demonstrate the currently accepted duplex ultrasound
      criteria for post-thrombotic change. We also document a new ultrasound finding
      which we describe as a chaotic phasic pattern of deep venous flow which was the
      only duplex evidence of post-thrombotic change in two of the cases. We suggest
      that its routine inclusion in duplex ultrasound assessment of the deep veins
      should be considered.

PMID- 8561711
TI  - A century of urinary tract radiology in Australasia.

PMID- 8561712
TI  - Calibration of entrance dose measurement for an in vivo dosimetry programme.
AB  - An increasing number of cancer treatment centres are using in vivo dosimetry as a
      quality assurance tool for verifying dosimetry as either the entrance or exit
      surface of the patient undergoing external beam radiotherapy. Equipment is
      usually limited to either thermoluminescent dosimeters (TLD) or semiconductor
      detectors such as p-type diodes. The semiconductor detector is more popular than
      the TLD due to the major advantage of real time analysis of the actual dose
      delivered. If a discrepancy is observed between the calculated and the measured
      entrance dose, it is possible to eliminate several likely sources of errors by
      immediately verifying all treatment parameters. Five Scanditronix EDP-10 p-type
      diodes were investigated to determine their calibration and relevant correction
      factors for entrance dose measurements using a Victoreen White Water-RW3 tissue
      equivalent phantom and a 6 MV photon beam from a Varian Clinac 2100C linear
      accelerator. Correction factors were determined for individual diodes for the
      following parameters: source to surface distance (SSD), collimator size, wedge,
      plate (tray) and temperature. The directional dependence of diode response was
      also investigated. The SSD correction factor (CSSD) was found to increase by
      approximately 3% over the range of SSD from 80 to 130 cm. The correction factor
      for collimator size (Cfield) also varied by approximately 3% between 5 x 5 and 40
      x 40 cm2. The wedge correction factor (Cwedge) and plate correction factor
      (Cplate) were found to be a function of collimator size. Over the range of
      measurement, these factors varied by a maximum of 1 and 1.5%, respectively. The
      Cplate variation between the solid and the drilled plates under the same
      irradiation conditions was a maximum of 2.4%. The diode sensitivity demonstrated
      an increase with temperature. A maximum of 2.5% variation for the directional
      dependence of diode response was observed for angle of +/- 60 degrees. In
      conclusion, in vivo dosimetry is an important and reliable method for checking
      the dose delivered to the patient. Preclinical calibration and determination of
      the relevant correction factors for each diode are essential in order to achieve
      a high accuracy of dose delivered to the patient.

PMID- 8561713
TI  - Brachytherapy in oesophageal carcinoma.
AB  - Patients with recurrent or locally advanced oesophageal carcinoma have a poor
      prognosis. Relief of dysphagia is often the goal of any further treatment.
      Several methods, including laser re-canalization, prosthetic intubation,
      dilatation, external beam irradiation (EBI) and intraluminal brachytherapy (IBT)
      can be used to alleviate dysphagia. In this retrospective review of 11 patients,
      eight with recurrent tumour and three newly diagnosed patients were treated with
      low dose rate IBT. Relief of dysphagia was achieved in nine patients, all of whom
      were able to maintain swallowing of at least a semi-solid diet until death or
      last follow-up. Toxicity was minimal, but survival was poor, with a median
      survival of only 3 months. IBT presents several advantages over other palliative
      methods, especially in recurrent tumours where re-treatment with EBI is often
      difficult because of normal tissue tolerance. Low dose rate IBT takes only 1-2
      days to deliver, is highly effective, has little morbidity and the palliation
      achieved is relatively durable.

PMID- 8561714
TI  - Heterotopic bone formation affecting the hip joint is preventable in high risk
      patients by post-operative radiation.
AB  - Between 1984 and 1993, 40 high risk patients (45 hips) received postoperative
      irradiation as prophylaxis against heterotopic ossification (HO). Radiotherapy
      was commenced within 5 days of the surgery in 43 of 45 hips. The development of
      HO was assessed by comparison of radiographic films prior to irradiation and at
      least 2 months after treatment (median interval 12 months). Progression of HO was
      observed in only two of 45 hips (4.3%) and of clinical significance in one
      (2.2%). Treatment was well tolerated with no acute complications or loosening of
      prosthetic components attributable to irradiation. During the study period, the
      treatment programme changed from 20 Gy in 10 fractions to 6-8 Gy in a single
      fraction, without loss of treatment efficacy. As well as improving resource
      utilization, single fraction techniques allow fewer patient transfers thereby
      reducing patient discomfort and risk of hip dislocation. This procedure is
      uncomplicated and should be considered more widely in the management of this
      disabling non-malignant condition.

PMID- 8561715
TI  - The estimation of lung dose from mid-perineum ionization chamber measurements in
      total body irradiations: a quality control check on dose delivery.
AB  - A series of patients (eleven males and eight females) receiving total body
      irradiation prior to bone marrow transplantation was monitored during treatment
      by recording the dose from an ionization chamber placed between the thighs in the
      mid-perineal region. The treatment was delivered by opposed lateral 6 MV photon
      beams. The patient was encompassed by the radiation field with the maximum
      collimator opening at a distance of 3.49 m from the X-ray focus to the patient
      mid-line. An analysis was made of the measured dose and the calculated percentage
      average lung dose for each patient in the series to seek a correlation between
      measured doses and patients' anatomical data so that estimates of delivered lung
      doses could be made. Whilst a global factor can be applied to measured dose to
      predict lung dose, it is concluded that perineal dose measurements distal to the
      region where dose is prescribed (mean lung dose) are sub-optimal for checks on
      target dose delivery. Entrance and exit dose measurements at the level of dose
      prescription (in the thorax) are preferable for more accurate predictions and
      quality control checks.

PMID- 8561716
TI  - The evolving role of radiation therapy in paediatric oncology, Philadelphia, USA,
      19-21 January 1995.
AB  - A summary of a conference reviewing recent developments and changes in the use of
      radiation therapy in paediatric oncology is reported. Although the use of
      radiation therapy has resulted in improved cure rates, the long-term
      complications of radiation in a paediatric population are recognised. More
      intensive systemic therapy and the increasing availability of prognostic data,
      including biological markers to tailor therapy to the individual patient, has
      resulted in a more selective use of radiation therapy. Changes in the management
      of specific tumour types are discussed.

PMID- 8561717
TI  - Non-functional malignant extra-adrenal retroperitoneal paraganglioma.
AB  - A case of malignant non-functional extra-adrenal retroperitoneal paraganglioma is
      presented. The mass was located in the peri-renal space, simulating a renal cell
      carcinoma. The radiological and pathological findings are discussed.

PMID- 8561718
TI  - Duodenal haemorrhage resulting from renal cell carcinoma metastases.
AB  - A case of duodenal haemorrhage resulting from renal cell carcinoma metastases is
      presented. This is an uncommon method of presentation and is often difficult to
      diagnose requiring multiple imaging regimes. This case demonstrates the problems
      that may be encountered in identifying the source of bleeding.

PMID- 8561719
TI  - Use of a Strecker oesophageal stent in the treatment of benign oesophageal
      stricture.
AB  - The use of self-expanding prostheses in the management of malignant oesophageal
      strictures has become well established. The majority of benign peptic oesophageal
      strictures can be successfully managed using endoscopic or fluoroscopically
      guided balloon oesophageal dilatation combined with long-term drug therapy,
      particularly using proton pumper inhibitors. Although endoscopic oesophageal
      dilatation can be performed on an outpatient basis, it requires repeated hospital
      visits. There is a small risk of oesophageal perforation whilst cardio
      respiratory complications may be encountered during the use of intravenous
      sedation in an elderly population. The use of a self-expanding Strecker stent in
      a 98 year old woman with a benign oesophageal stricture is described.

PMID- 8561720
TI  - Bizarre parosteal osteochondromatous proliferation of the hands and feet.
AB  - Two adults with bizarre parosteal osteochondromatous proliferation of the hands
      and feet are presented. The preoperative diagnosis may be difficult to make and
      the correct diagnosis was not made in either case until pathological examination
      of recurrent tumour masses occurred. The radiological and pathological features
      of this lesion are discussed. The diagnostic features which differentiate this
      condition from other causes of new bone formation in the peripheries are
      described.

PMID- 8561721
TI  - Metastatic carcinoma infiltrating lung mimicking BOOP.
AB  - A 38 year old female with treated carcinoma of the breast presented with a
      clinical and radiological diagnosis of bronchiolitis obliterans organising
      pneumonia. Based on these findings a biopsy was not performed and she was treated
      with steroids. Following lack of response to steroid therapy a lung biopsy was
      performed showing peribronchiolar, lymphatic, venular and arteriolar metastatic
      carcinoma. Her symptoms responded to chemotherapy. Interstitial and intracellular
      spread of carcinoma should be considered in the differential diagnosis of the
      radiological appearance of BOOP, and therefore a histological diagnosis should be
      obtained to determine appropriate management.

PMID- 8561722
TI  - Radiological imaging of a massive dermoid in the male pelvis.
AB  - A dermoid cyst, arising from the posterior aspects of the prostate and seminal
      vesicles, and extending into the pelvis to masquerade as a full bladder, must be
      exceedingly rare. Ultrasound, computed tomography and especially magnetic
      resonance imaging (MRI) proved to be invaluable in making the diagnosis, and MRI
      in particular was very useful in providing an anatomical road map for surgery.

PMID- 8561724
TI  - Case quiz.

PMID- 8561723
TI  - Bone marrow cellularity: quantification by chemical-shift misregistration in
      magnetic resonance imaging and comparison with histomorphometrical techniques.
AB  - The accuracy of a technique that uses chemical-shift misregistration in magnetic
      resonance (MR) imaging to quantify vertebral bone marrow cellularity was tested
      on cadaveric specimens. In order to estimate the cellularity of 11 unfixed
      vertebral bodies, mid-sagittal MR images were obtained using a 1.5T magnet with a
      proton-density-weighted spin-echo sequence (repetition time/echo time, 2500/22
      ms) and a narrow bandwidth. These values were subsequently compared to the
      histomorphometrical values for cellularity, amount of trabecular bone and
      deposited iron. The image-derived values for cellularity (VI, %) correlated well
      with values determined by histomorphometry (VH, %) (VI = 21.2 + 0.72 VH, r =
      0.92) regardless of the presence of trabecular bone and small amount of stored
      iron in the specimens. This simple technique may be applicable in the estimation
      of marrow cellularity.

PMID- 8561725
TI  - Malignant lympho-epithelial lesion of the salivary gland.

PMID- 8561726
TI  - Gastric stapling and gastric banding: the radiological differences.

PMID- 8561727
TI  - The effect of plasmid acquisition on potential virulence attributes of
      Pasteurella multocida.
AB  - Several plasmids that were isolated from complement-resistant Pasteurella
      multocida or Escherichia coli were evaluated for phenotypic markers. Plasmid
      p2267, isolated from a tetracycline-resistant, complement-resistant fowl cholera
      field isolate of P. multocida (PM2267), was used to transform a K-12 E. coli
      (C600); this resulted in increased complement resistance, which was eliminated by
      curing. Either of two plasmids (p1870 or p70-1, isolated from P. multocida and E.
      coli, respectively) conferred an increase in complement resistance and
      invasiveness to turkey epithelial cells when expressed in the Clemson University
      (CU) vaccine strain of P. multocida. Additionally, the CU strain containing p1870
      was more virulent in turkey challenge, and the plasmid appeared amplified in
      vivo. No detectable differences in major outer-membrane proteins, capsule, or
      carbohydrate fermentation were found to be associated with the acquisition of
      these plasmids.

PMID- 8561728
TI  - Observations on the relationship in chickens between the virulence of some avian
      influenza viruses and their pathogenicity for various organs.
AB  - Comparative histological and immunocytochemical studies were conducted on
      formalin-fixed tissues from chickens infected with avian influenza viruses of
      varying virulence. Results showed a distinct pattern of disease that depended on
      the virulence of the virus and the susceptibility of the birds. At 3 days post
      intranasal inoculation with a highly virulent H7N7 virus, all 6-to-8-week-old
      specific-pathogen-free (SPF) birds were affected, and all developed pancreatic
      necrosis and encephalitis associated with specific immunoperoxidase staining.
      Other same-aged SPF birds were only occasionally affected 6 to 8 days after
      intravenous inoculation with almost avirulent H4N4, H6N2, or H3N8 virus. Specific
      lesions and immunoperoxidase staining were noted in the kidneys only. The H7N7
      virus in older commercial birds and an H7N3 virus in young SPF and older
      commercial birds caused intermediate mortality rates at 4 to 11 days
      postinoculation, and there was a broad range of lesions and specific
      immunoperoxidase staining in the pancreas, brain, kidney, heart, and skeletal
      muscle. Two exceptional birds had immunostaining of small blood vessels
      throughout their bodies with or without lesions or staining in the tissues, which
      may have represented a transitory pre-localizing phase occurring in many birds.
      There was necrosis without virus antigen detection in the bursae, thymuses, and
      cecal tonsils, possibly secondary to stress or only transitory infection of
      virus. These data indicate that rapid, retrospective diagnosis of avian influenza
      in fixed tissues is possible by using an immunoperoxidase test on pancreas,
      brain, and kidney.

PMID- 8561729
TI  - Identification of Mycoplasma synoviae immunogenic surface proteins and their
      potential use as antigens in the enzyme-linked immunosorbent assay.
AB  - Specific immunogenic proteins of Mycoplasma synoviae (MS) strain WVU-1853 were
      purified and characterized by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and by Western transfer using anti-MS, anti-M. gallisepticum, and
      non-immune chicken sera. A cluster of prominent immunoreactive proteins with
      molecular masses from 46 to 52 kDa (p46-52) and less reactive single proteins of
      approximately 22 and 92 kDa were shown to partition into the detergent phase of
      Triton X-114 MS lysates, suggesting that these amphiphilic polypeptides are
      integral membrane proteins. Monoclonal antibodies, produced by immunizing mice
      with MS whole cell proteins and shown to bind species-specific determinants,
      reacted strongly with p46-52 and less intensely with the 22-kDa protein, but they
      did not react with the 92-kDa protein. A protein fraction extracted from the
      Triton X-114 detergent phase and further purified by ion-exchange chromatography
      was found to be highly enriched in p46-52 and was used as antigen in a prototype
      enzyme-linked immunosorbent assay (ELISA) to detect MS antibodies. Seventy serum
      samples were taken variously from specific-pathogen-free chickens experimentally
      infected with MS or MG and from commercial broiler breeder chickens vaccinated
      for MS and MG. All samples were tested by both rapid serum agglutination and a
      prototype ELISA described herein; the two tests were strongly correlated (r =
      0.776). The results indicate that the ELISA antigen used--the immunodominant cell
      surface proteins in the p46-52 cluster--appears to be a good candidate for use in
      the development of improved rapid diagnostics of MS infections in birds.

PMID- 8561730
TI  - Comparison of environmental monitoring protocols for the detection of Salmonella
      in poultry houses.
AB  - Environmental monitoring has been used as a screening method to detect Salmonella
      enteritidis infection in laying hens. Several transport protocols (buffered
      peptone water, skim milk, asparagine, double distilled water, and no media), to
      be used for the detection of Salmonella in environmental samples from poultry
      houses, were compared for their ability to preserve the integrity of specimens.
      The isolation rates of Salmonella using the various transport protocols,
      including double-strength skim milk and no media (dry), were similar. Use of dry
      swabs is more convenient than a media transport system and should be adopted as
      an alternative method.

PMID- 8561731
TI  - Dose titration study of enrofloxacin (Baytril) against respiratory colibacillosis
      in Muscovy ducks.
AB  - Four-week-old specific-pathogen-free Muscovy ducks were inoculated with reovirus.
      One week later, they were inoculated intratracheally with a O78:K80 strain of
      Escherichia coli. The next day, they were given enrofloxacin at different doses
      in the drinking water. Comparison of mortality rates, weight gain, macroscopic
      lesions, and E. coli re-isolations among treated and untreated birds showed that
      a 5-day treatment course with 12.5 or 25 ppm enrofloxacin in water for 4 hours in
      the morning provided good therapeutic efficacy against respiratory
      colibacillosis.

PMID- 8561732
TI  - Experimental reproduction of endocarditis with Pasteurella gallinarum in mature
      leghorn chickens.
AB  - The pathogenicity of Pasteurella gallinarum for mature leghorn chickens was
      investigated by inoculating thirty 52-week-old chickens intravenously with live
      P. gallinarum. Each chicken was inoculated once daily for 5 days at one of three
      different dosage levels with either the type strain ATCC 13361 or a field isolate
      from a chicken with endocarditis. Chickens were necropsied after death or
      euthanasia. Valvular endocarditis was present in seven chickens given the field
      isolate and five chickens given the type strain. Other lesions detected were
      myocarditis, hepatic and splenic infarcts, nephritis, pneumonia, and
      encephalitis. At necropsy, P. gallinarum was reisolated from hearts, livers,
      spleens, lungs, kidneys, and blood. Controls injected with sterile broth had no
      lesions of endocarditis, nor was P. gallinarum isolated from them. The results
      confirm the pathogenicity of P. gallinarum for the heart valves of mature
      chickens.

PMID- 8561733
TI  - Comparison of neutralizing epitopes among infectious bursal disease viruses using
      radioimmunoprecipitation.
AB  - Monoclonal antibodies (MAbs) were used to analyze the relatedness of neutralizing
      epitopes of infectious bursal disease virus (IBDV) strains. The MAb B69
      neutralized the homologous D78 virus but not the MD and Del-A variant strains of
      IBDV. MAbs 33E8 and R63 neutralized D78 and variant strains MD and Del-A. A cDNA
      clone consisting of a 1000-base-pair fragment of the VP2 gene from the Del-A IBDV
      strain was translated using an in vitro system. Six peptides were observed
      following translation, which represented a full-length product (35.5 kilodaltons)
      and five truncated products. The translated peptides were radioimmunoprecipitated
      using MAbs B69, 33E8, and R63. Only MAb R63 immunoprecipitated the in vitro
      translation products from Del-A. MAbs B69 and 33E8 did not immunoprecipitate the
      in vitro-translated VP2 peptides. The D78 and Del-A viruses were radiolabeled in
      vivo using 35S-methionine. Proteins from these viruses were examined by
      radioimmuno-precipitation with MAbs B69, 33E8, and R63. Although the background
      made interpretation of the results difficult for MAb B69, this MAb clearly
      immunoprecipitated VP2 of D78. MAb 33E8 immunoprecipitated the D78 VP3 protein,
      and R63 immunoprecipitated the VP2 protein. MAb R63 also immunoprecipitated the
      35S-methionine-labeled VP2 protein from Del-A. It was concluded that the
      neutralizing epitope represented by 33E8 was located on VP3 and that the epitope
      represented by R63 is located on both classic and variant viruses in the region
      of VP2 that is generally thought to contain sequence variability among IBDV
      strains.

PMID- 8561734
TI  - The effect of route of inoculation on protection by killed vaccines in chickens.
AB  - The effect of various routes of immunization on protection against challenge by
      virulent agents was examined in chickens. Chickens were immunized
      intratracheally, intranasally, per os, by crop gavage, and intramuscularly.
      Agents examined were killed Haemophilus paragallinarum, Mycoplasma gallisepticum,
      and infectious bursal disease virus. Results of immunization by intratracheal
      administration were equivalent to those produced by parenteral administration.
      All vaccines effectively induced production of serum antibodies against
      pathogens, and all immunized chickens were protected against infection by each
      pathogen.

PMID- 8561735
TI  - A recombinant fowlpox virus expressing the envelope antigen of subgroup A avian
      leukosis/sarcoma virus.
AB  - A recombinant fowlpox virus (FPV) was constructed by inserting cloned sequences
      from Schmidt-Ruppin subgroup A avian sarcoma virus coding for the viral envelope
      (env) antigen into a nonessential region of FPV DNA downstream from a synthetic
      promoter. Sera from chickens hyperimmunized with the recombinant FPV neutralized
      the infectivity of the homologous subgroup A virus (RCASBP/AP) but only weakly
      neutralized the infectivity of Rous sarcoma virus, another subgroup A avian
      leukosis virus. Similarly, vaccination of 1-day-old chicks with this recombinant
      FPV protected against infection with RCASBP/AP virus but not against infection
      with another subgroup A Rous-associated virus (RAV-1). These results show that
      such a recombinant FPV can be used to protect chickens against avian leukosis
      virus and confirm previous observations that a type-specific antigenic
      variability existed within the subgroup A avian leukosis/sarcoma virus group.

PMID- 8561736
TI  - Tissue tropism and replicative properties of waterfowl-origin influenza viruses
      in chickens.
AB  - Waterfowl-origin influenza (WFOI) viruses were evaluated for their tissue tropism
      and replicative properties in chickens. The 14 WFOI isolates used in this study
      represented 13 different hemagglutinin-neuraminidase combinations recovered
      during 1987 and 1988 and included isolates possessing the H5 and H7 hemagglutinin
      subtypes and one isolate possessing the H5N2 combination. Following intravenous
      challenge, the frequencies of virus recovery within individual experiments were
      generally higher for the lower digestive tract and kidney samples. Virus titers
      ranged up to 10(8.5) mean embryo infective doses per gram of kidney tissue in
      clinically normal chickens. Differences in frequencies of virus recovery and
      virus titers in tissues indicated that some of these uniformly nonpathogenic and
      low-pathogenicity WFOI virus isolates replicated more extensively in chickens
      than did others. This enhanced ability to replicate in chickens should be further
      evaluated as a potential factor associated with the threat WFOI viruses present
      to poultry.

PMID- 8561737
TI  - Replication of infectious laryngotracheitis virus in a quail cell line, QT-35.
AB  - The relative resistance of the quail fibroblastic cell line QT-35 to infection by
      infectious laryngotracheitis virus (ILTV) was circumvented by the continual
      passaging of infected cells in the presence of uninfected monolayers. Such virus
      containing cells were used to extend the infection to an otherwise refractory
      quail liver cell line IQ1A, as well as to a normally permissive chicken liver
      cell line LMH, with nearly equal efficiency. In contrast, extracellular virus
      that had been derived from either QT-35 or IQ1A cells could not readily infect
      either quail cell line, although LMH cells were still susceptible. Therefore, the
      block to ILTV replication in quail cells is probably at the
      adsorption/penetration stage.

PMID- 8561738
TI  - Synergism between chicken anemia virus (CAV) and avian reovirus following dual
      infection of 1-day-old chicks by a natural route.
AB  - One-day-old specific-pathogen-free white leghorn chicks were dually infected with
      the Cux-1 isolate of chicken anemia virus (CAV) and separate avian reovirus
      strains (S1133 or Uchida) by an oral route. Fourteen days after inoculation,
      chicks were bled, and packed cell volumes (PCVs) were determined. Chicks were
      also weighted and examined for macroscopic changes to the bone marrow, thymus,
      and bursa of Fabricius. The results obtained following dual inoculation of chicks
      with CAV and reovirus were compared with results obtained from mock-infected
      chicks or chicks inoculated with CAV or reovirus alone. Chicks dually infected
      with CAV and the S1133 reovirus strain had significantly (P < 0.05) lower weight
      gain and more severe tissue damage than chicks inoculated with either virus
      alone. In addition, a significant (P < 0.05) reduction in the mean PCV was seen
      in these dually infected chicks when compared with chicks inoculated with CAV
      alone. No increase in the severity of the disease signs was observed following
      dual infection with CAV and reovirus strain Uchida.

PMID- 8561739
TI  - Characterization of cell-mediated responses to Eimeria acervulina antigens.
AB  - In order to identify antigens from Eimeria acervulina eliciting cell-mediated as
      well as humoral immune responses, merozoite and sporozoite fractions were
      separated by electrophoresis and injected into chickens. Coccidia-specific
      antibody titers, lymphocyte proliferation, and interferon production were
      measured to determine whether the inoculations sensitized the chickens to
      merozoites and sporozoites. Several fractions from merozoites and sporozoites
      induced humoral or cell-mediated responses. Merozoite fraction 4 (molecular
      weight [MW] 12,700-18,400) had the most consistent high interferon production; it
      also had good antibody production after challenge but not before challenge.
      Merozoite fraction 3 (MW 18,400-29,000) elicited high antibody titers and modest
      proliferation. Merozoite fraction 2 (MW 29,000-43,000) elicited consistently high
      proliferation; however, antibody responses were normal and interferon production
      was lower than that in the control. Merozoite fraction 5 (MW 6000-12,700) results
      were modest for all three parameters. Sporozoite fractions 5 and 6 (MW 12,700
      29,000) elicited good antibody titers after challenge. The only sporozoite
      fraction that showed any interferon induction, fraction 2 (MW 69,000-200,000),
      also elicited good proliferation, although it did not stimulate antibody
      production. Sporozoite fraction 1 (> 200,000 MW) had very high proliferation
      potential. These findings support the hypothesis that different antigens
      preferentially elicited different T-cell responses.

PMID- 8561740
TI  - Effect of lactose and Lactobacillus acidophilus on the colonization of Salmonella
      enteritidis in chicks concurrently infected with Eimeria tenella.
AB  - The effect of dietary lactose and Lactobacillus acidophilus on the colonization
      of Salmonella enteritidis (phage type 4) in newly hatched leghorn chicks
      concurrently infected with Eimeria tenella was studied. There were six groups of
      birds in each of two replicate trials: uninfected controls, birds infected with
      S. enteritidis, birds infected with S. enteritidis and E. tenella, birds infected
      with S. enteritidis and E. tenella that were fed with dietary lactose (5%), birds
      infected with S. enteritidis and E. tenella that were provided with L.
      acidophilus, and birds infected with S. enteritidis and E. tenella that were fed
      both L. acidophilus and dietary lactose (5%). Chickens were necropsied at 2, 5,
      and 8 days after S. enteritidis inoculation for bacteriological examination. The
      cecal population of S. enteritidis was significantly increased by infection with
      E. tenella. Lactose alone and the combination of lactose and L. acidophilus
      significantly reduced the population of S. enteritidis in the ceca of birds
      infected with E. tenella (P < 0.05), but the combination was more effective than
      lactose alone (P < 0.05). Adding anaerobic culture of L. acidophilus alone did
      not significantly decrease the population of S. enteritidis in the ceca. No
      significant reduction of colonization of S. enteritidis in the liver and spleen
      of birds with coccidiosis was observed.

PMID- 8561741
TI  - A comparative study of avian reovirus pathogenicity: virus spread and replication
      and induction of lesions.
AB  - This study examined the relationship of avian reovirus spread and replication to
      induction of lesions and the relevant role of the S1 segment encoding a virus
      neutralizing antigen. One-day-old broiler chickens were infected via footpad or
      orally with two virus strains (883 and 176) that differ greatly in virulence and
      a reassortant (R44) that has the S1 segment from 176 and the remaining genome
      segments from 883. Virus replication and histological lesions in various tissues
      (heart, liver, spleen, kidney, bursa, hock joint, and bone marrow) were measured
      at 2-day intervals until day 8 postinoculation. The virulent strain 176 spread to
      and replicated efficiently in all tissues examined and caused extensive and
      severe lesions, whereas the mild strain 883 was detected only in tissues near
      inoculation sites and caused only minimal lesions. The appearance of lesions
      correlated with the presence of viral replication in each tissue tested.
      Together, these results indicate that induction of lesions, or pathogenicity, is
      directly related to virus spread and replication. Reassortant R44 behaved like
      strain 176 in chicken embryo fibroblasts (CEFs), i.e., both replicated much
      faster and produced larger plaques than strain 883. In broiler chickens, however,
      R44 behaved like strain 883, replicating and inducing lesions to an extent that
      was fat lower than that of strain 176. These results suggest that the S1 segment
      alone is capable of determining viral replication and plaque formation in
      cultured CEFs but is not sufficient to determine the virus spread and replication
      and the pathological change in broiler chickens.

PMID- 8561742
TI  - The comparative virulence for chicks of Salmonella enteritidis phage type 4
      isolates and isolates of phage types commonly found in poultry in the United
      States.
AB  - Phage type 4 Salmonella enteritidis has been associated with morbidity and
      mortality in broiler chickens in the United Kingdom. The recent isolation of this
      phage type from poultry in the United States has raised concerns about whether
      the current regulatory approach to S. enteritidis should be modified to consider
      phage type 4 differently from other phage types. The present study assessed and
      compared the virulence of phage type 4 S. enteritidis isolates, S. enteritidis
      isolates of other phage types, and an S. pullorum isolate in both single-comb
      white leghorn and white Plymouth Rock chicks. The mean incidence of severe
      illness or death following oral inoculation with phage type 4 S. enteritidis was
      significantly lower than the incidence associated with S. pullorum inoculation in
      both lines of chicks. Nevertheless, some individual phage type 4 S. enteritidis
      isolates caused severe effects at a frequency similar to that of S. pullorum in
      single-comb white leghorn chicks. In general, severe morbidity or mortality
      following infection with S. enteritidis isolates of all phage types tested
      occurred more often in single-comb white leghorn chicks than in white Plymouth
      Rock chicks. The mean frequency at which chicks were severely affected following
      inoculation with phage type 4 isolates was significantly higher than the mean for
      isolates of other phage types. However, in both lines of chicks, some significant
      differences in virulence were apparent within the set of phage type 4 strains
      tested. The observed virulence for chicks of recent U.S. poultry isolates of
      phage type 4 S. enteritidis was similar to that of earlier isolates from various
      sources, including poultry isolates from the United Kingdom.

PMID- 8561743
TI  - A highly sensitive, broad-spectrum infectivity assay for infectious bursal
      disease virus.
AB  - In order to develop an infectivity assay for infectious bursal disease virus
      (IBDV), an enzyme-linked immunosorbent assay (ELISA) for detecting IBDV antigens
      was developed using a rabbit antiserum to IBDV. The ELISA detected both serotypes
      1 and 2 of IBDV, purified virus proteins at a concentration of about 0.1 ng/well
      and about 10(4) to 10(5) infectious units/well, and was about 10(3) times more
      sensitive than an agar gel precipitin test. By using the ELISA for detecting IBDV
      antigens in the cultured fluids, infectivity titration could be determined within
      5 days of cultivation in seven of the 10 virus-cell combinations when chicken
      embryo fibroblasts (CEFs), BGM-70 cells, and LSCC-BK3 cells were used. IBDV
      antigens were not detected in three combinations remaining after 7 days of
      cultivation. When 18 IBDV strains, including highly virulent, classically
      virulent, and attenuated strains, were tested for growth in four types of cells
      using the ELISA, eight strains in CEFs, seven strains in chicken kidney cells,
      five strains in BGM-70 cells, and 17 strains in LSCC-BK3 cells were detected.
      These results indicated that LSCC-BK3 cells had the broadest spectrum for IBDV.
      When 26 field bursal homogenates were tested for infectious IBDV using LSCC-BK3
      cells, all 19 field IBDV isolates that were detected by immunostaining of the
      cells were also detected by the ELISA. These results indicate that this
      infectivity assay for IBDV using LSCC-BK3 cells and the ELISA has a high
      sensitivity and a broad spectrum for IBDV and is especially useful for large
      scale applications.

PMID- 8561744
TI  - Pasteurella multocida isolated from wild birds of North America: a serotype and
      DNA fingerprint study of isolates from 1978 to 1993.
AB  - Serotype and DNA fingerprint methods were used to study Pasteurella multocida
      isolated from 320 wild birds of North America. Isolates were collected during
      1978-93. The HhaI profiles of 314 isolates matched the HhaI profile of somatic
      reference type 1, stain X-73; somatic type 1 antigen was expressed by 310
      isolates, and the serotype of four isolates was undetected. Differentiation of
      the 314 isolates was observed by digestion of DNA with HpaI. None of the HpaII
      profiles matched the HpaII profile of X-73 (designated HhaI 001/HpaII 001). Three
      HpaII profiles were recognized among the somatic type 1 isolates: HpaII 002 (n =
      18), HpaII 003 (n = 122), and HpaII 004 (n = 174). Profile HpaII 002 was found
      among isolates collected during 1979-83. Profile HpaII 003 was identified from
      isolates collected during 1979-89, with the exception of two isolates in 1992.
      The HpaII 004 profile was identified from isolates collected during 1983-93. Of
      the six remaining isolates, four expressed somatic type 4 and had HhaI profiles
      identical to the somatic type 4 reference strain P-1662 profile (designated HhaI
      004); these isolates were differentiated by digestion of DNA with HpaII. One
      isolate was identified as serotype F:11, and another was serotype A:3,4. In the
      present study, 314 of 316 (99.4%) isolates from wild birds in the Central,
      Mississippi, and Pacific flyways during 1978-93, were P. multocida somatic type
      1.

PMID- 8561745
TI  - DNA fingerprint analysis of standard, intermediate, and variant antigenic types
      of Salmonella enterica subspecies enterica serovar Gallinarum biovar pullorum.
AB  - DNA fingerprint profiles and antigenic types of 150 Salmonella enterica serovar
      Gallinarum biovar pullorum field isolates and seven reference strains were
      evaluated. Field isolates were submitted to the National Veterinary Services
      Laboratories (NVSL), Ames, Iowa, between Oct. 1, 1990, and Aug. 20, 1991. Three
      antigenic types (standard [n = 96], intermediate [n = 50], and variant [n = 4])
      were identified among the field isolates. The NciI fingerprint profiles of all
      field isolates were identical. Differentiation of field isolates was observed by
      digestion of DNA with HpaII; three profiles were recognized. One HpaII profile
      (designated SP HpaII 001) was common among 144 isolates (standard, n = 90;
      intermediate, n = 50; and variant, n = 4); the remaining six pullorum standard
      type isolates were equally dispersed between two HpaII profiles (designated SP
      HpaII 002 and 003). Three antigenic types were identified among the seven
      reference strains (reference strains 11, 17, 19, and 20 [standard]; reference
      strain 4 [intermediate]; reference strains 79 and 296 [variant]). One NciI
      profile was recognized; two HpaII profiles were observed. Six reference strains
      (11, 17, 19, 20, 79, and 296) had profile SP HpaII 001, and reference strain 4
      had profile SP HpaII 002. No correlations were established between DNA
      fingerprints and antigenic types.

PMID- 8561746
TI  - Relationship of sex, age, and concurrent intestinal disease to necrotic enteritis
      in turkeys.
AB  - A retrospective case-control study of necrotic enteritis in turkeys was done.
      Male flocks were involved in a significantly greater proportion of necrotic
      enteritis cases compared with control cases. Necrotic enteritis cases occurred
      most frequently between 6 and 11 weeks of age. Within this age range, the
      probability of a necrotic enteritis case having a concurrent intestinal disease
      diagnosis was significantly higher than the probability in control cases.
      Coccidiosis was the most frequently diagnosed concurrent intestinal disease with
      necrotic enteritis, followed by clinical hemorrhagic enteritis and ascaridiasis.

PMID- 8561748
TI  - Evaluation of persistence and distribution of Salmonella serotype isolation from
      poultry farms using drag-swab sampling.
AB  - The consistency and persistence of isolation of specific serotypes of Salmonella
      were evaluated on a 31-farm broiler complex following four complete sampling
      periods. A total of 25 different serotypes were isolated, with multiple serotypes
      and were frequently isolated simultaneously from individual farms. When the
      serotypes recovered from individual farms were further examined, common serotypes
      were isolated from individual farms on only seven occasions. Furthermore, on only
      five occasions were multiple serotypes recovered from individual farms on
      consecutive samplings. A casual association of common serotype isolations among
      farms with similar flock placement dates was observed in one sampling period.
      These results indicate little predictability or consistency of Salmonella
      serotype isolation on individual farms over time.

PMID- 8561747
TI  - Detection of Mycoplasma gallisepticum, M. synoviae, and M. iowae by multi-species
      polymerase chain reaction and restriction fragment length polymorphism.
AB  - A single set of oligonucleotide primers was designed from known 16S ribosomal RNA
      (rRNA) sequences of Mycoplasma gallisepticum (MG), M. synoviae (MS), and M. iowae
      (MI). This set of primers selectively amplifies a 780-base-pair DNA fragment
      within the 16S rRNA gene of MG, MS, and MI but does not amplify other avian
      mycoplasmas or other bacteria. The detection limit of the multi-species
      polymerase chain reaction (PCR) was approximately 100 mycoplasma (MG, MS, MI)
      colony-forming units per PCR reaction. The PCR product was differentiated by
      restriction fragment length polymorphism with the restriction enzymes HpaI,
      HpaII, and MboI. Preliminary results from field samples suggest that this
      technique could be a useful and rapid diagnostic test for the detection of these
      three pathogenic poultry mycoplasmas.

PMID- 8561749
TI  - Detection of proteolytic bacteria in the upper respiratory tract flora of
      poultry.
AB  - Proteolytic bacteria were readily demonstrated among the upper respiratory tract
      flora of poultry in two chicken flocks and two turkey flocks. Between 20% and 50%
      of birds in each flock had highly proteolytic bacteria in the upper respiratory
      tract flora, and the amount of the bacterial flora determined to be highly
      proteolytic in any given bird ranged from none to a majority. Highly proteolytic
      bacteria recovered included five species of staphylococci, as well as two gram
      negative bacterial species, Flavobacterium sp. and Vibrio alginolyticus. All
      species of staphylococci isolated have previously been recovered from animal
      sources, whereas Flavobacterium sp. and V. alginolyticus are usually reported to
      be associated with soil and surface-water origins. The protocols used to screen
      for proteolytic bacteria among the flora and to assess protease activity required
      minimal supplies and equipment.

PMID- 8561750
TI  - Egg dipping in hydrogen peroxide solution to eliminate Salmonella typhimurium
      from eggshell membranes.
AB  - The effectiveness of egg dipping in a 6% hydrogen peroxide solution to eliminate
      Salmonella typhimurium from eggshell membranes was evaluated. The first step was
      to assess the water uptake from broiler hatching eggs dipped in tap water once or
      twice using a positive-pressure differential method in order to determine the
      best method to use in the disinfection trials. Double dipping increased water
      uptake by 86% more than single dipping. Dipping S. typhimurium-contaminated eggs
      twice in a 6% hydrogen peroxide solution reduced the average number of organisms
      in eggshell membranes by 95% and the number of S. typhimurium-positive eggs by
      55% compared with the infected untreated group. Dipping the eggs in a 6% hydrogen
      peroxide solution did not adversely affect hatchability.

PMID- 8561751
TI  - Fatty liver-hemorrhagic syndrome observed in commercial layers fed diets
      containing chelated minerals.
AB  - This study was originally conducted to determine the effect of various chloride
      levels and consumption of chelated versus non-chelated minerals on egg production
      and eggshell breaking strength. However, the focus of this report changed after
      fatty liver-hemorrhagic syndrome (FLHS) was observed in hens that consumed diets
      containing chelated minerals. No FLHS was observed in hens that consumed a diet
      that contained non-chelated minerals. Four hundred thirty-two 35-week-old
      commercial laying hens were housed in individual cages in groups of nine hens
      each. The treatments were factorially arranged (3 x 2) such that six experimental
      diets differing in chloride levels and in source of minerals were fed for six 28
      day laying periods. A significantly higher mortality attributed to FLHS was
      observed in hens that consumed the diets having chelated minerals as compared
      with hens that consumed the diets with non-chelated minerals. No difference in
      mortality was observed among the hens fed the various chloride diets.

PMID- 8561752
TI  - Relationship between body-weight gain after movement of chickens to an unfamiliar
      cage and response to Escherichia coli challenge infection.
AB  - One day after chickens were moved from a brooder to unfamiliar cages, there was a
      high negative correlation (p < 0.001) between an individual's body-weight gain
      and the severity of response to Escherichia coli challenge infection.

PMID- 8561753
TI  - Salinomycin toxicosis in male breeder turkeys.
AB  - A sudden outbreak of mortality in one house of 600 48-week-old male breeder
      turkeys on a five-house turkey breeder farm was suspected to be feed-related. The
      turkeys gasped and became recumbent; 21.7% of affected turkeys died. No
      significant gross lesions were found at necropsy. Histological lesions, limited
      to skeletal muscle, consisted of degeneration and necrosis and were judged
      compatible with ionophore toxicosis. Feed samples from the affected house were
      analyzed by three techniques and shown to contain 13.4 to 18.4 g of salinomycin
      per ton of feed. An error at the feed mill was blamed for allowing contamination
      of the turkey feed with broiler starter feed containing salinomycin.

PMID- 8561754
TI  - Esophageal and proventricular cryptosporidiosis in a chicken.
AB  - Examination of hematoxylin-and-eosin-stained sections of chicken esophagus and
      proventriculus revealed Cryptosporidium-colonized surface squamous and mucous
      gland columnar epithelial cells. This chicken also had malignant lymphoma
      (lymphosarcoma). The hypothesis that infection by Cryptosporidium sp. was either
      preceded by or followed by herpesvirus infection, immunosuppression, and
      neoplasia cannot be refuted. Clinicians and pathologists should be aware that
      esophageal and proventricular cryptosporidiosis can occur in chickens; they
      should also be aware that mild inflammation and necrosis can accompany
      parasitism.

PMID- 8561755
TI  - Combined adenovirus and rotavirus enteritis with Escherichia coli septicemia in
      an emu chick (Dromaius novaehollandiae).
AB  - A 2-week-old emu chick (Dromaius novaehollandiae) of approximately 200 g body
      weight was presented for necropsy with a history of weakness, diarrhea, pallor of
      the head, and acute death. Hemorrhagic enteritis with mild hepatomegaly was noted
      on gross examination. Microscopic examination revealed necrohemorrhagic enteritis
      with intralesional intranuclear basophilic viral inclusion bodies in intestinal
      epithelial cells; splenic lymphoid necrosis and fibrin exudation; hepatocellular
      vacuolar change; and multiple clusters of small gram-negative bacilli in the
      liver, spleen, yolk sac, and intestine. Transmission electron microscopy of
      negatively stained fecal specimens and thin sections of small intestine revealed
      clusters of viral particles consistent with adenovirus and rotavirus. Attempts at
      viral isolation from pooled tissue specimens were unsuccessful. Escherichia coli
      was isolated from specimens of liver and intestine and from an abdominal swab.

PMID- 8561756
TI  - Apparent selenium toxicity in emus (Dromaius novaehollandiae).
AB  - A commercial emu breeder experienced high embryonic mortality during the 1992-93
      breeding season, apparently associated with high levels of selenium. The feed was
      a mixture of catfish food supplemented with a vitamin E and selenium premix. The
      mixture contained an average of 1.4 ppm selenium. Selenium analysis was conducted
      on eggs from several hens laid during the period of vitamin and selenium
      supplementation and after the supplementation was withdrawn. Initial egg selenium
      levels ranged from 1.2 to 7.1 ppm, with a mean value of 4.2 +/- 0.7 ppm (n = 9).
      Eggs collected over a 2-month period post-withdrawal contained 2.1 +/- 0.2 ppm
      selenium (n = 6). Eggs sampled between 2 and 3 months post-withdrawal contained
      1.1 +/- 0.1 ppm selenium (n = 4). Egg selenium levels decreased significantly
      over the 3-month period (P < 0.05) for each individual sample.

PMID- 8561757
TI  - Esophagitis due to a herpesvirus associated with mortality in a psittacine
      aviary.
AB  - In a disease outbreak at a psittacine aviary, eight Pionus sp. and Amazon parrots
      became sick. Three of four Amazon parrots died with severe esophagitis, and
      epithelial intranuclear inclusion bodies containing herpesvirus were prominent.
      Focal liver necrosis with rare hepatocyte intranuclear inclusion bodies were
      found in two of the dead Amazon parrots.

PMID- 8561758
TI  - Hemoglobinuric nephrosis in a rhea (Rhea americana).
AB  - An eighteen-month-old female rhea (Rhea americana) was presented dead for
      necropsy. The owner reported having observed blood in the droppings. Gross
      examination revealed a rhea in good body condition with a copious amount of frank
      blood in the cloaca. Large masses of matted fescue grass (Festuca spp.) distended
      the ventriculus and jejunum. No hemorrhage was evident in the digestive tract,
      which was otherwise void of ingesta. The kidneys were dark brown in color. Renal
      histopathology revealed a severe accumulation of eosinophilic pigment in the
      tubular epithelial cells of the proximal convoluted tubules, with tubular
      nephrosis and eosinophilic casts in the collecting tubules. It was concluded that
      the renal pigment was hemoglobin and not myoglobin, based on lack of evidence of
      muscle injury and the severe erythrophagocytosis evident in hepatic macrophages.
      The renal pigment also stained positive with the hemoglobin-specific Okajima
      stain. Hemoglobinuric nephrosis has not previously been reported in an avian
      species.

PMID- 8561759
TI  - Who develops PTSD from motor vehicle accidents?
AB  - Within 1 to 4 months of their motor vehicle accident (MVA), we assessed 158 MVA
      victims who sought medical attention as a result of the MVA. Using the Clinician
      Administered PTSD Scale (CAPS: Blake, Weathers, Nagy, Kaloupek, Klauminzer,
      Charney & Keane, 1990. National Center for Post-Traumatic Stress Disorder,
      Boston, MA)., we found that 62 (39%) met DSM-III-R (American Psychiatric
      Association, 1987. Washington, DC: American Psychiatric Press) criteria for Post
      Traumatic Stress Disorder. Using variables from the victim's account of the
      accident and its sequelae, pre-MVA psychosocial functioning, demographic
      variables, pre-MVA psychopathology and degree of physical injury, we found that
      70% of the subjects could be classified as PTSD or not with 4 variables: prior
      major depression, fear of dying in the MVA, extent of physical injury and whether
      litigation had been initiated. Using multiple regression to predict the
      continuous variable of total CAPS score, as a measure of post-traumatic stress
      symptoms, we found that 8 variables combined to predict 38.1% of variance
      (Multiple R = 0.617).

PMID- 8561760
TI  - Situation-specific child control: a visit to the dentist.
AB  - This paper describes the development of the Child Dental Control Assessment
      (CDCA), a situationally-specific measure of control strategies for school-age
      children visiting the dentist. A pilot proceeded two definitive studies. In the
      pilot, the instructions and a battery of items were pretested. The first study
      was with 180 children and gathered data in a classroom setting to establish the
      psychometric characteristics of the instrument. Factor analysis, accounting for
      over 50% of the variance, suggested five scales: Dentist-Mediated Control, Active
      Coping, Cognitive Withdrawal, Reassurance, and Physical Escape. Internal
      consistency of the scales constructed from the factors ranged from 0.5 to 0.7.
      The highest standardized scale scores were for Reassurance and Dentist-Mediated
      Control. Younger children reported a greater need for Active Coping. In the
      second study in a clinical setting, children completed an assessment battery and
      were trained to use a signalling device. Higher CDCA scores for the Active Coping
      scale, but not the other scales, were associated with the use by subjects of a
      device to signal the dentist. The proposed measure allows assessment of
      individual differences among children of the same age as well as developmental
      differences between age groupings of children.

PMID- 8561762
TI  - Gender and age differences in the prevalence of specific fears and phobias.
AB  - Point prevalence of specific fears and phobias was determined in 704 respondents
      of 1000 randomly selected adults aged 18-70 yr. A phobia for lightning, enclosed
      spaces, darkness, flying, heights, spiders, snakes, injections, dentists and/or
      injuries was defined if subjects reported a fear that was out of conscious
      control, interfered with life and lead to the avoidance of the feared object
      [American Psychiatric Association, 1994. Diagnostic and statistical manual of
      mental disorders (4th edn). Washington, DC: American Psychiatric Press.] Fear
      intensity was assessed using visual analogue scales. A factor analysis generally
      supported the classification of fears and phobias into: (1) situational phobias
      (lightning, enclosed spaces, darkness, flying and heights); (2) animal phobias
      (spiders and snakes); and (3) mutilation phobias (injections, dentists,
      injuries). Total point prevalence of any specific phobia was 19.9% (26.5% for
      females and 12.4% for males). In total, 21.2% women and 10.9% men met criterias
      for any single specific phobia. Multiple phobias was reported by 5.4% of the
      females and 1.5% of the males. Animal phobia had a prevalence of 12.1% in women
      and 3.3% in men. Point prevalence of situational phobia was 17.4% in women and
      8.5% in men. For mutilation phobia no gender difference was observed, being
      presented in 3.2% of the women and 2.7% of the men. Women as compared to men gave
      higher fear ratings for all objects and situations. Inanimate object fears and
      phobias were more common in older than younger individuals. Animal fears were
      more intense in younger than in older individuals. Fear of flying increased and
      fear of injections decreased as a function of age in women but not in men. Thus,
      specific fears and phobias are heterogeneous with respect to sex and age
      distribution.

PMID- 8561761
TI  - The meaning of psychological symptoms: effectiveness of a group intervention with
      hypochondriacal patients.
AB  - A group treatment for hypochondriasis was administered to 14 subjects. It was
      based on Barsky, Geringer and Wool (1988) [General Hospital Psychiatry, 10, 322
      327] cognitive-behavioral formulation and presented as an educational course to
      explain the origins of an enhanced perception of somatic symptoms. Initially, one
      experimental group (N = 9) and a waiting list control (N = 8) were formed.
      Experimental subjects showed significant reductions in illness fears and
      attitudes, reported somatic symptoms and dysfunctional beliefs. Waiting-list
      controls also changed some illness attitudes, but showed no change in somatic
      symptoms and increased the number of visits to doctors. Experimental and control
      subjects differed on several change measures. Afterwards, part of the waiting
      list subjects (N = 5) received treatment. Overall, treatment was effective for
      the target measures and produced long-term positive effects on other fears,
      dysphoric mood and well-being. After treatment, subjects were significantly more
      extroverted, open and warm. The clinical impression was that treatment was not
      limited to less severe cases.

PMID- 8561763
TI  - Follow-up results of supportive versus behavioral therapy for illicit drug use.
AB  - Follow-up data (mean 9 months) were obtained for 74 subjects who had been treated
      for a mean of 8 months and 17 sessions in a controlled comparison of Behavioral
      vs Supportive Counselling for drug abuse. Based on urinalysis, self-report, and
      family report, all subjects (100%) were actively using drugs at pre-treatment.
      During the last month of treatment, 81% of the Supportive treatment subjects and
      44% of the Behavioral treatment subjects were using drugs at least once. At the
      follow-up month, drugs were used at least once by 71% of the Supportive vs 42% of
      Behavioral subjects. When drug use was measured in terms of the number of days of
      use per month, Supportive counselled subjects did not decrease drug use either by
      the end of treatment or at follow-up; for Behavioral subjects, drug use decreased
      by 63% by the end of treatment and by 73% at follow-up. Alcohol use, and days
      worked/or in school showed a similar pattern of greater improvement for the
      Behavioral treatment being maintained at the follow-up. These results indicate a
      substantial treatment-specific reduction of drug usage that endures after
      treatment is discontinued. The present favorable results appear attributable to
      the inclusion of family/significant others in therapy and the use of
      reinforcement contingent on urinalysis results.

PMID- 8561764
TI  - Symptom subtypes of obsessive-compulsive disorder in behavioral treatment
      studies: a quantitative review.
AB  - Recent reviews and meta-analytic studies have provided an encouraging account of
      the effectiveness of behavioral interventions for obsessive-compulsive disorder
      (OCD). One question regarding these estimates concerns their degree of
      generalizability to the range of OCD subtypes encountered in clinical settings.
      The purpose of the present study was to provide a quantitative description of the
      prevalence of various OCD subtypes (i.e. type of compulsions) within the
      behavioral treatment literature. We examined 65 studies that permitted
      classification of patients according to symptom subtype. Patients with primarily
      cleaning and/or checking compulsions predominated, accounting for 75% of the
      treatment population. On the other hand, patients with multiple compulsions or
      other compulsions, such as exactness, counting, hoarding, or slowness rituals
      were underrepresented, comprising only 12% of the population, which is markedly
      less than clinical epidemiological estimates. Rates of improvements in patients
      with OCD are most applicable to patients with cleaning and checking compulsions,
      but may not yet be generalizable to patients with other symptoms. These findings
      encourage studies of the efficacy of existing and novel interventions for
      patients with counting, repeating, symmetry, hoarding, or multiple compulsions in
      order to broaden the clinical application of OCD behavioral treatment.

PMID- 8561765
TI  - Attentional bias in obsessional compulsive disorder.
AB  - To date, studies of information processing in anxiety disorders have suggested
      that the latter are characterised by vigilance for threatening stimuli, possibly
      specific to personally relevant threat content. The present study represents an
      attempt to establish whether patients suffering from Obsessional Compulsive
      Disorder (OCD), generally classified as an anxiety disorder, show a similar
      cognitive bias. Thus, a replication of MacLeod, Mathews and Tata's (1986) study
      [Journal of Abnormal Psychology, 95, 15-20] is reported, employing modified
      materials of direct concern to the OCD subjects i.e. Contamination-related words.
      The results did indeed reveal content specific vigilance, whereby the OCD group
      were more vigilant for contamination content than mood-matched High Trait Anxious
      (HTA) controls, but the reverse was true for Social Anxiety words. Additionally,
      while a general threat interference effect was identified for both OCD and HTA
      subjects this was not content specific. A second experiment employing Low Trait
      Anxious subjects revealed no vigilance for threat nor any threat interference in
      this sample. The clinical implications and possible mechanism underlying these
      results are discussed.

PMID- 8561766
TI  - Examination of a three-dimensional drinking motives questionnaire in a young
      adult university student sample.
AB  - The literature on drinking motives suggests that individuals drink for three
      distinct reasons: coping motives (CM: to reduce and/or avoid negative emotional
      states); social motives (SM: to affiliate with others); and enhancement motives
      (EM: to facilitate positive emotions). Cooper, Russell, Skinner and Windle (1992)
      [Psychological Assessment, 4, 123-132] developed a 3-dimensional self-report
      instrument, the Drinking Motives Questionnaire (DMQ), with subscales designed to
      assess relative frequency of drinking for each of these three motives. This study
      was designed to examine the psychometric properties of the DMQ in a large sample
      of young adult university students. Three hundred and fourteen students
      voluntarily served as subjects; 266 students (85% of the total sample; 196F and
      70M) reported drinking on the DMQ. These students were divided into two age
      groups [20 yr and under (n = 117); 21 yr and older (n = 149)]. Analyses of
      variance indicated: (a) main effects of gender, with men scoring significantly
      higher on the DMQ-EM subscale and tending to score higher on the DMQ-SM subscale
      when compared to women; (b) a main effect of age group on the DMQ-EM subscale,
      with younger students scoring significantly higher than older students; and (c) a
      significant main effect of drinking motive, with the most relatively frequent
      drinking reported for SM and the least for CM overall. Although mild-to-moderate
      shared variance between subscales was noted, the three subscales of the DMQ were
      found to possess adequate-to-high levels of internal consistency. A confirmatory
      factor analysis (CFA) showed that the hypothesized 3-factor model provided a
      better fit than either a unidimensional or 2-factor model in explaining the
      underlying structure of the DMQ. Some suggestions for improvements in DMQ item
      content are made. The present results replicate and extend previous findings by
      Cooper and colleagues to a sample of university students, and support the utility
      of using the DMQ in future investigations of the drinking motives of young
      adults.

PMID- 8561767
TI  - Behavioral avoidance test for obsessive compulsive disorder.
AB  - Few treatment outcome studies of Obsessive Compulsive Disorder (OCD) have
      employed Behavioral Avoidance Tests (BATs) to assess changes in symptomatology,
      probably because of the difficulty of constructing such tests for a disorder
      which has widely varying symptoms. The few studies that have examined the
      psychometric properties of BATs for OCD have found mixed evidence for validity
      but good treatment sensitivity. The present study presents psychometric findings
      for a multi-step/multi-task BAT that assessed percentage of steps completed,
      subjective anxiety, global avoidance, and rituals. This measure was used with 50
      clients diagnosed with OCD whose symptoms varied widely. The BAT demonstrated
      good convergent and divergent validity, as well as treatment sensitivity
      according to effect size calculations. A composite score combining steps, anxiety
      level, avoidance and rituals also performed well in psychometric tests.
      Strategies to reduce the complexity of scoring are presented, along with examples
      of several BAT tasks to enable researchers to employ this behavioral measure.

PMID- 8561768
TI  - The assessment of obsessive-compulsive phenomena: psychometric and normative data
      on the Padua Inventory from an Australian non-clinical student sample.
AB  - The Padua Inventory (PI) is a measure of obsessive-compulsive phenomena, which is
      used in clinical and research settings. One reason for the PI's growing
      acceptance is the emergence of a good deal of evidence supporting the adequacy of
      its reliability, convergent validity, and evidence supporting the stability of
      its factor structure. However, there have been some concerns about its
      discriminant validity. The use of the PI in Australia has been limited by the
      lack of local normative data and information about its psychometric properties.
      The cross-national validation of the PI has both theoretical and practical
      implications, and could add further evidence for its adequacy as a measure of
      obsessive-compulsive phenomena. Results from the present study found that the PI
      exhibited a similar but not identical factor structure compared to previous
      studies, consistently good reliability, adequate convergent validity, and
      differences in normative data compared with previous studies. Overall, while one
      may not necessarily assume the generalisability of normative data across
      different cultural contexts, there is a good deal of consistency in the
      psychometric properties of the PI. However, there is a need to further
      demonstrate the PI's discriminant validity, particularly for the "Urges and
      Worries" subscale.

PMID- 8561769
TI  - Hoarding and obsessive-compulsive symptoms.
AB  - The present study attempts to extend recent research on the relation between
      hoarding and obsessive-compulsive experiences. In both college student and
      community samples, hoarding was associated with higher scores on the Yale-Brown
      Obsessive-Compulsive Scale (YBOCS). The relationship was stronger among the
      community sample, in which there was a greater range of compulsive symptoms and
      hoarding behavior. Hoarding was also associated with higher levels of general
      psychopathology as measured by the Brief Symptom Inventory but not by the
      Obsessive-Compulsive Personality Disorder subscale from the Millon Clinical
      Multiaxial Inventory-II or by a measure of ordinary risk taking. Among a sample
      of patients with obsessive-compulsive disorder (OCD), 31% reported hoarding
      obsessions and 26% reported hoarding compulsions on the YBOCS symptom checklist.
      These frequencies are similar to those found elsewhere and suggest that, although
      not as frequent as the classical symptoms of OCD, hoarding is a common symptom
      among OCD patients.

PMID- 8561770
TI  - Functional communication training for the treatment of multiply determined
      challenging behavior in two boys with autism.
AB  - Functional communication training was used to replace multiply determined problem
      behavior in two boys with autism. Experiment 1 involved a functional analysis of
      several topographies of problem behavior using a variation of the procedures
      described by Iwata, Dorsey, Slifer, Bauman, and Richman. Results suggested that
      aggression, self-injury, and disruption were multiply determined (i.e.,
      maintained by both attention and access to preferred objects). Experiment 2
      involved a multiple-baseline design across subjects. The focus of intervention
      was to replace aggression, self-injury, and disruption with functionally
      equivalent communicative alternatives. Both boys were taught alternative "mands"
      to recruit attention and request preferred objects. Acquisition of these
      alternative communication skills was associated with concurrent decreases in
      aggression, self-injury, and disruption. Results suggest that multiply determined
      challenging behavior can be decreased by teaching an alternative communication
      skill to replace each assessed function of the problem behavior.

PMID- 8561771
TI  - A specific inhibitor of cytosolic phospholipase A2 activity, AACOCF3, inhibits
      glucose-induced insulin secretion from isolated rat islets.
AB  - In pancreatic beta-cells, arachidonic acid accumulation results primarily from
      phospholipid hydrolysis by phospholipase A2, and activation of this enzyme has
      been shown to accompany glucose-induced insulin secretion. Inhibitors of
      phospholipase A2 attenuate the secretory response, although the compounds used to
      date have not discriminated between cytosolic and secretory isoforms of
      phospholipase A2. In this work, the specific cytosolic phospholipase A2
      inhibitor, AACOCF3, caused a dose-dependent inhibition of glucose-induced insulin
      secretion from isolated rat islets and this response was significantly relieved
      by exogenous arachidonic acid. The results suggest that, despite the low levels
      of expression of cytosolic phospholipase A2 in rat islets, this enzyme
      contributes to the control of glucose-induced insulin secretion in rat pancreatic
      beta-cells.

PMID- 8561772
TI  - Regulation of the potassium current and cytosolic Ca2+ release induced by 2
      methylthio ATP in hippocampal neurons.
AB  - A potent P2Y purinoceptor agonist, 2-methylthio ATP (2-MeSATP), produced whole
      cell potassium currents through a purinoceptor linked to a pertussis toxin (PTX)
      insensitive G-protein in rat hippocampal neurons. The currents were not affected
      by a selective protein kinase C or A inhibitor. Single channel recordings
      demonstrated that the potassium channel is activated without latency even in
      outside-out patches. These suggest that the channel may be regulated directly by
      the beta gamma subunits of a G-protein. In addition, 2-MeSATP enhanced
      intracellular free Ca2+ concentration ([Ca2+]i) with a very rapid initiation
      time. The [Ca2+]i increase was inhibited by a broad G-protein inhibitor, but not
      by a phospholipase C (PLC) inhibitor or an IP3 receptor antagonist. These
      indicate that this Ca2+ mobilization may be regulated by a mechanism independent
      of a PLC-mediated phosphatidylinositol signaling pathway.

PMID- 8561773
TI  - Differential expression of ob mRNA in rat adipose tissues in response to insulin.
AB  - The recently cloned obese (ob) gene encodes a fat-specific mRNA and a protein
      which is believed to regulate satiety and metabolic rate so as to control fat
      storage. In the present study we investigated rat ob mRNA levels in different fat
      depots and the effects of insulin infusion on ob mRNA expression. Northern blot
      analysis showed the abdominal fat (epididymal and perirenal fat pads) had higher
      ob mRNA levels than subcutaneous fat. After a 2.5-hr infusion of insulin into
      fasted rats, ob mRNA levels were increased by 3.0 and 1.9-fold in epididymal and
      perirenal fat pads, respectively. However, no change of ob mRNA level was
      observed in the subcutaneous fat depot. These data demonstrate adipose depot site
      specific expression of ob mRNA and support the hypothesis that insulin plays an
      important role in the expression of ob mRNA.

PMID- 8561774
TI  - Osteogenic protein-1 is required for mammalian eye development.
AB  - Osteogenic Protein-1 (OP-1/BMP-7) is a bone morphogenetic protein in the
      transforming growth factor-beta superfamily and has been shown to be expressed
      temporally and spatially during epithelial-mesenchymal interactions mediating
      tissue morphogenesis in early embryogenesis. In order to identify the primary
      role(s) for OP-1 in development, we carried out whole rat embryo cultures, over a
      72-h period from primitive streak stages to early limb bud stages, in rat sera
      containing either OP-1 blocking antibodies (10 micrograms/ml) or nonreactive IgG.
      Rat embryos cultured with control antibodies developed normally, while those
      cultured with anti-OP-1 antibodies consistently exhibited over-all reduced size
      and absence of eyes. Histological sections revealed a greater reduction in neural
      retina development in the embryos treated with anti-OP-1 blocking antibodies. In
      situ hybridization and immunolocalization analyses indicate that OP-1 is
      expressed in the neuroepithelium of the optic vesicle at E11.5, is limited to the
      presumptive neural retina and developing lens placode, and is subsequently
      expressed in the neural retina, lens and developing cornea at E12.5-E13.5. Our
      results indicate that OP-1 mediates the inductive signals involved in mammalian
      eye development.

PMID- 8561775
TI  - Hypoxic effects on the expression of mineralocorticoid and glucocorticoid
      receptors in human renal cortex epithelial cells.
AB  - The effects of both mild and severe hypoxic conditions on the expression of
      mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the primary
      human renal cortex epithelial cells (RCEC) were investigated. Slot blot analyses
      were performed with human beta-actin cDNA and the cDNA probes for unique regions
      of MR and GR. The steady-state mRNA level of the house-keeping beta-actin gene
      remains the same in RCEC under either normoxic or hypoxic conditions. However,
      there was a 45% reduction in MR expression and a 30% increase in GR expression,
      under mild hypoxic condition (15% O2) over 3 days. Furthermore, cells subjected
      to a severe hypoxic condition (0.5% O2) for 24 hours exerted a 22% reduction in
      MR expression and a 64% increase in GR expression. Changes in MR and GR
      expression may, in part, explain the physiological changes in adrenal cortical
      function observed in hypoxic conditions.

PMID- 8561776
TI  - Hsp70 family molecular chaperones and mutant insulin receptor: differential
      binding specificities of BiP and Hsp70/Hsc70 determines accumulation or
      degradation of insulin receptor.
AB  - We have examined the binding specificities of Hsp70 family molecular chaperones,
      BiP and Hsp70/Hsc70, to wild-type or mutant insulin receptors. BiP bound to
      proreceptor of wild-type insulin receptor, but not to mature receptor. A mutant
      insulin receptor, which lacked 47 amino acid residues (delta Ex13 IR)
      corresponding to exon 13 of insulin receptor gene, accumulated in the endoplasmic
      reticulum as uncleaved proreceptor with immature oligosaccharide chains. This
      deletion mutant bound to BiP more tightly than wild type. Introduction of two
      types of mutations, Asp1179 or Leu1193, into delta Ex13 IR led to accelerated
      degradation, and these double mutants bound weakly to BiP. In contrast, Ser735
      insulin receptor was normally transported to the plasma membrane and normally
      bound to BiP. Furthermore, Asp1179, Leu1193 insulin receptors and delta Ex13 IR
      combination mutant with either Asp1179 or Leu1193 bound more tightly to
      Hsp70/Hsc70 compared with wild-type, Ser735, and delta Ex13 IR. These results
      suggest that the binding specificity of mutant insulin receptors to two molecular
      chaperones, i.e., BiP and Hsp70/Hsc70, plays an important role for their
      posttranslational processing that may lead to the accumulation in the endoplasmic
      reticulum or the degradation of insulin receptors.

PMID- 8561777
TI  - Protein folding within and protein transport into mammalian microsomes are
      differentially affected by photoaffinity labeling of microsomes with 8-azido-ATP.
AB  - Transport of presecretory proteins into mammalian microsomes involves a
      microsomal protein which is sensitive to photoaffinity labeling with 8-azido-ATP.
      Typically, protein folding within the lumen of the endoplasmic reticulum of
      mammalian cells depends on ATP and the member of the Hsp70 protein family, BiP.
      Here we addressed the question of whether protein transport into and folding
      within microsomes are differentially affected by photoaffinity labeling of
      microsomes with 8-azido-ATP. Folding of heterodimeric luciferase to the native
      state was more azido-ATP-sensitive compared to transport of the precursors of the
      two subunits. Therefore, we conclude that the microsomal protein which is
      responsible for the ATP-dependence of protein folding in the endoplasmic
      reticulum is sensitive to photoaffinity labeling with 8-azido-ATP and that this
      microsomal protein is distinct from the microsomal ATP-binding protein which is
      involved in protein transport.

PMID- 8561779
TI  - Inhibition of NF-AT signal transduction events by a dominant-negative form of
      calcineurin.
AB  - An inhibitory, "dominant-negative," form of the calcineurin catalytic (A) subunit
      was prepared, which lacks the calmodulin-binding domain, autoinhibitory domain
      and most of its catalytic core but possesses the regulatory (B) subunit binding
      domain. When tested for its ability to block calcineurin-dependent signaling in
      Jurkat cells, expression of this "B-subunit knock-out" (BKO) construct suppressed
      reporter gene activity driven by NF-AT, the pivotal promoter element for
      interleukin (IL)-2 gene induction. Immunoprecipitation of epitope-labeled BKO
      demonstrated for the formation of a tight complex with endogenous B subunit in
      Jurkat cells, consistent with an inhibitory mechanism that involves the
      sequestration of the B subunit. Furthermore, the sharply reduced NF-AT activity
      produced by co-transfecting BKO could be "rescued" by overexpression of
      transfected B subunit, suggesting that depletion of this subunit was responsible
      for the inhibition. These data suggest the potential utility of agents that
      disrupt calcineurin-mediated signal transduction pathways by blocking formation
      of the catalytically active dimer of calcineurin A and B subunits.

PMID- 8561778
TI  - Inhibition of the H+/peptide cotransporter in the human intestinal cell line Caco
      2 by cyclic AMP.
AB  - Treatment of Caco-2 cells with cholera toxin inhibits the activity of the
      H+/peptide cotransporter. The effect of cholera toxin is mimicked by E. coli heat
      labile enterotoxin, forskolin and isobutylmethylxanthine and is associated with
      an increase in cAMP levels in the cells. The inhibition is due to a decrease in
      the maximal velocity of the transport system. Inhibitors of protein kinase A and
      protein kinase C block the effect of cholera toxin. Interestingly, the H+/peptide
      cotransporter in Caco-2 cells does not possess any putative site for
      phosphorylation by protein kinase A but does possess sites for phosphorylation by
      protein kinase C. It appears that the cAMP-dependent inhibition of the H+/peptide
      cotransporter in Caco-2 cells is mediated through activation of protein kinase C.

PMID- 8561780
TI  - Effects of hyperthyroidism on expression of a phosphoenolpyruvate
      carboxykinase/bovine growth hormone gene in transgenic mice.
AB  - Thyroid hormone (T3) responsiveness of the PEPCK promoter in vivo was examined in
      both PEPCK/bGH(460) and PEPCK/bGH(335) mouse lines. Transgenic and non-transgenic
      littermates were treated with methimazole or PTU for 6 or 4 weeks, respectively,
      then treated +/- T3 for 10 days. In PEPCK/bGH(460) and PEPCK/bGH(355) transgenic
      mice, the bGH mRNA was decreased by 65% and 46%, respectively, in hyperthyroid
      mice when compared to euthyroid controls. Endogenous PEPCK mRNA was decreased by
      33% in hyperthyroid non-transgenic mice. The conclusion of this study is that
      chronic hyperthyroidism in mice inhibits PEPCK-directed expression of the
      transgene when either the -460/+73 or the -355/+73 promoter/regulatory elements
      are used.

PMID- 8561781
TI  - Thiophosphate derivatives as inhibitors of tyrosine phosphatases.
AB  - Thiophosphorylated proteins or peptides are poor substrates of protein
      phosphatases. As a competitive inhibitor of a protein tyrosine phosphatase, a
      tyrosine-thiophosphorylated nonapeptide ENDYINASL displays a KI value of 0.25
      microM, in comparison with the Km value of 3.1 microM exerted by the enzyme
      toward the phosphorylated form of the peptide. Furthermore, adenosine 5'-O-3
      thiotriphosphate is also an effective competitive inhibitor of the enzyme with a
      KI value of 1.4 microM. In contrast, ATP and 5'-adenylimidodiphosphate are much
      less effective, indicating that the thiophosphate group plays a major role in the
      inhibition process. Further supporting this is the fact that sodium thiophosphate
      is a more effective inhibitor than inorganic phosphate (IC50 = 0.47 mM versus 15
      mM). The inhibition by thiophosphate compounds is specific for PTPs. The data
      suggest the application of thiophosphate derivatives as specific inhibitors of
      PTPs.

PMID- 8561782
TI  - Cloning and sequence analysis of the cDNA for a protein from Coccidioides immitis
      with immunogenic potential.
AB  - We have cloned and sequenced the cDNA encoding an immunoreactive protein from the
      pathogenic fungus Coccidioides immitis which stimulates human T cells and has
      been associated with protective vaccines in mice. The transcript contained an
      open reading frame encoding 194 amino acids with a calculated molecular weight of
      19.5 kDa, a 151 base 5' untranslated region (UTR), and a 468 base 3'UTR. A four
      member repeat motif, usually thr-ala-glu-pro, exists for amino acids 98 through
      141. Deduced amino acid sequence derived from the cDNA was identical with
      previously determined internal amino acid sequence from the native protein, and
      goat antiserum raised against the purified fungal protein reacted with an
      inducible fusion protein translated from this cDNA. Using this cDNA to produce
      recombinant protein will allow direct testing of its role in human immunity to
      coccidioidomycosis and may lead to new diagnostic tests.

PMID- 8561783
TI  - Glucocorticoid regulation of androgen binding protein expression in primary
      Sertoli cell cultures from rats.
AB  - Glucocorticoids are known to inhibit testicular function, and its receptor is
      also localized in the Sertoli cells. To evaluate possible role of glucocorticoid
      in Sertoli cells, the effects of dexamethasone on the expression of androgen
      binding protein (ABP) have been investigated in primary Sertoli cell cultures.
      Dexamethasone increased ABP mRNA levels, with maximal stimulation reached at 36
      hr. The induction of ABP mRNA was dependent on the low concentration (10(-8) and
      10(-7) M) of dexamethasone but gradually reduced in the cells treated with high
      concentration (10(-6) and 10(-5) M). Dexamethasone-induced ABP mRNA level was no
      change in the cells after addition of cycloheximide but almost reduced by
      actinomycin-D pretreatment. Steady-state levels of ABP mRNA gradually increased
      in the Sertoli cells prepared from 14- and 21-days of age corresponding to rat
      puberty, and ABP mRNA was induced by dexamethasone. These results suggest that
      ABP gene is transcriptionally regulated by dexamethasone in primary Sertoli cell
      cultures.

PMID- 8561784
TI  - Identification of the five essential histidine residues for peptidylglycine
      monooxygenase.
AB  - Peptidylglycine monooxygenase (PGM) is a copper-containing monooxygenase that
      plays a key role in the peptide C-terminal alpha-amidation. Comparative analysis
      of the amino acid sequences of rat, human, bovine and frog PGMs revealed that ten
      histidines (residues 107, 108, 172, 235, 242, 244, 279, 364, 366 and 367 in rat
      PGM) are conserved among the four species. We introduced site-directed mutations
      to the ten histidines of rat PGM and found that the mutation of His- 107-->Ala,
      His-108-->Ala, His-172-->Ala, His-242-->Arg or His-244-->Ala abolished the enzyme
      activity. The five mutant proteins lacking the enzyme activity bound to a
      substrate, Phe-Gly-Phe-Gly, as did the wild type PGM. These results along with
      available evidence indicate that the five histidine residues (His-107, 108, 172,
      242 and 244) are essential for PGM activity, acting as copper ligands.

PMID- 8561785
TI  - Shear stress activates cytosolic phospholipase A2 (cPLA2) and MAP kinase in human
      endothelial cells.
AB  - Intracellular signalling events that govern endothelial responses to shear are
      incompletely defined. In this study confluent human endothelial cells were
      subjected to shear. At shear levels of 1.04, 2.92, 5.31 and 8.3 dynes/cm2, which
      are in the range of those that occur in vessels in venous and arterial
      circulations, the activity of cPLA2 was increased above control levels. To
      examine pathways by which cPLA2 may be activated in response to shear, we assayed
      the p42 isoform of MAP kinase (ERK-2) and found increased activity in cells
      exposed to shear. Our findings demonstrate for the first time that cPLA2 and MAP
      kinase p42 are activated by shear in human endothelial cells, and add to evidence
      from other systems that indicates that the two enzymes have related signalling
      functions.

PMID- 8561786
TI  - Choline phosphate and phorbol ester potentiate the mitogenic effect of insulin by
      competitive mechanisms in NIH 3T3 fibroblasts.
AB  - Treatments of serum-starved NIH 3T3 fibroblasts with either 100 nM phorbol-12
      myristate 13-acetate (PMA) or 1 mM choline phosphate (ChoP) greatly enhanced, in
      a mutually inhibitory manner, the stimulatory effect of insulin on DNA synthesis.
      Wortmannin and GF 109203X, inhibitors of phosphatidylinositol 3'-kinase and
      protein kinase C, respectively, inhibited only the combined mitogenic effects of
      PMA and insulin, but not that of ChoP and insulin. In the presence of 0.5% fetal
      calf serum, both ChoP and insulin, but not PMA, retained their mitogenic
      activities, while PMA abolished the stimulatory effect of insulin on DNA
      synthesis. The results indicate that PMA can both enhance and inhibit the
      mitogenic action of insulin, depending on the presence of serum factors and ChoP.

PMID- 8561787
TI  - Enzymatic synthesis of the N-glycosidic bond by beta-aspartylation of
      glycosylamines.
AB  - Glycosylasparaginase (EC 3.5.1.26) is an amidase, which cleaves the N-glycosidic
      linkage during glycoprotein degradation leading to the liberation of L-aspartic
      acid from various glycoasparagines. In this work we demonstrate that
      glycosylasparaginase is also capable of catalyzing the synthesis of the N
      glycosidic bond by N-beta-aspartylation of beta-glycosylamine using 1-amino-N
      acetylglucosamine as the nucleophile and L-aspartic acid beta-methyl ester as the
      beta-aspartyl donor. Kinetic studies indicated that beta-glycosylamine has 1390
      fold higher reactivity than water in the de-beta-aspartylation of the beta
      aspartylenzyme, indicative of the presence of a beta-glycosylamine binding sub
      site at the substrate binding site of glycosylasparaginase. The reaction can be
      applied to glycosylaparaginase-catalyzed biosynthesis of novel glycoasparagines.

PMID- 8561788
TI  - Chromosomal localization and 5' sequence of the human protein serine/threonine
      phosphatase 5' gene.
AB  - Protein phosphorylation plays a crucial role in the regulation of a wide array of
      proteins involved in many cellular processes. Protein phosphatase 5 (PP5) is a
      novel member of the protein serine/threonine phosphatase family. The majority of
      the cDNA sequence of PP5 has been reported recently. In our study, a sequence
      encoding the whole open reading frame of PP5 was cloned from a human fetal brain
      cDNA library. The protein phosphatase cDNA sequence of our clone is longer at the
      5' end than the recently published sequence. It's likely that the extended
      sequence contains the start codon ATG, since a translation stop codon TAG is
      present upstream of the ATG codon in the same open reading frame. The mRNA of the
      PP5 gene was detected in all the human tissues examined. The PP5 gene was
      localized to human chromosomal region 19q13.3.

PMID- 8561790
TI  - The relation between two molecular species of P-450 in adult testis and 17 alpha
      hydroxylase and 17,20-lyase activities.
AB  - Two P-450s from adult pig testis were purified to specific contents of 11.2 and
      12.0 nmol P-450/mg protein and shown to have minimum molecular weights of 45,000
      and 46,000, respectively. The absorption spectra were typical of P-450s. The P
      450s were separated from the two fractions by CM-C50 Sephadex column
      chromatography. One P-450 (M(r) = 45000) exhibited 17,20-lyase activity of 6.78
      nmol of androstenedione/min/nmol P-450, on incubation with 17 alpha
      hydroxyprogesterone as a substrate. The other P-450 (M(r) = 46,000) exhibited no
      17,20-lyase activity. Both P-450s exhibited 17 alpha-hydroxylase activity that
      amounted to 10 nmol of steroid products. Accordingly, the two molecular species
      of P-450 are thus markedly different in 17,20-lyase activity toward 17 alpha
      hydroxyprogesterone.

PMID- 8561789
TI  - Superinduction of NF-kappa B by actinomycin D and cycloheximide in epithelial
      cells.
AB  - Epithelial cells are actively involved in inflammation and play a role in
      inflammatory diseases such as asthma. Numerous proinflammatory genes, expressed
      in the airway epithelium, are regulated by the transcription factor NF-kappa B.
      We show that the proinflammatory cytokines, IL-1 beta and TNF alpha, as well as a
      protein kinase C activator cause NF-kappa B activation in A549 epithelial cells.
      This observation is consistent with a major role for NF-kappa B in inflammation.
      We also demonstrate that IL-1 beta costimulation with a protein synthesis
      inhibitor, cycloheximide, or a transcription blocker, actinomycin D, results in
      superinduction of NF-kappa B but not the transcription factors Oct 1, AP-1, and
      Sp-1. We speculate that this may be due to lack of de novo synthesis of the NF
      kappa B inhibitor, I kappa B alpha, and suggest that this phenomena may help
      explain the widely observed effect of mRNA superinduction of primary response
      genes in response to translational blockers.

PMID- 8561791
TI  - Talin can crosslink actin filaments into both networks and bundles.
AB  - The talin-actin interaction was examined by using negative staining and
      cosedimentation assays. At pH 6.4 and low ionic strength, talin extensively
      crosslinked actin filaments into both networks and bundles. The bundles consist
      of parallel actin filaments with a center-to-center distance of 13 nm, and talin
      crossbridges spaced at 36-nm intervals along the bundles. As pH was increased
      stepwise from 6.4 to 7.3, talin's bundling activity was decreased first, then its
      networking activity. Qualitatively similar results were obtained at pH 6.4 by
      increasing ionic strength. Chemical crosslinking indicated talin was present as a
      dimer from pH 6.4 to 7.3, with or without added KC1. The results show that talin
      can interact directly with actin filaments by formation of actin filament
      networks and bundles, with the bundles more sensitive to dissolution by increase
      in pH or ionic strength.

PMID- 8561792
TI  - Proliferation and differentiation of PC12 cells were affected by p21ras GTPase
      activating proteins and its deletion mutant proteins.
AB  - In this study, a mammalian expression vector containing cDNA of human GAP
      (p120GAP) or its deletion mutant was transfected into PC12 cells. The deletion
      mutant peptide has SH2 and SH3 domains, but no GTPase activating domain. Cells
      stably overexpressing intact p120GAP showed enhanced proliferation, demonstrated
      by 5-bromo-2'-deoxyuridine labeling and cell cycle analysis. On the other hand,
      in cells expressing the deletion mutant GAP, differentiation induced by NGF was
      potentiated, as demonstrated by enhanced acetylcholinesterase activity and
      induction of neurofilament proteins.

PMID- 8561793
TI  - Nucleotide sequence of salicylate hydroxylase gene and its 5'-flanking region of
      Pseudomonas putida KF715.
AB  - The salicylate hydroxylase, a flavoprotein monooxygenase, catalyzes the
      decarboxylative hydroxylation of salicylate to form catechol. Nucleotide sequence
      of a salicylate hydroxylase gene and its 5'-flanking region in chromosomal DNA of
      Pseudomonas putida KF715 was analyzed. The salicylate hydroxylase was encoded in
      an open reading frame with 1308 base pairs which can encode a polypeptide of
      molecular weight 48 kDa with 435 amino acids. The open reading frame was preceded
      by a putative ribosome-binding sequence. A predicted amino acid sequence of the
      salicylate hydroxylase exhibited 84% identity with corresponding enzyme encoded
      in NAH7 plasmid, and 20 to 30% homologies with other similar flavoprotein
      monooxygenases. A 5'-flanking sequence of the salicylate hydroxylase gene
      exhibited extensive homology with promoter and nahR-binding site of sal operon in
      NAH7 plasmid.

PMID- 8561794
TI  - Molecular cloning of Xenopus activin type I receptor and the analysis of its
      expression during embryogenesis.
AB  - We cloned cDNAs coding for the Xenopus counterparts of a type I activin receptor.
      The cDNA clones were predicted to encode 56kd proteins, namely XAR3 and XAR4
      proteins. The two proteins are highly homologous to each other, showing 96%
      identity in the amino acid sequences. The GST-fused kinase domain of XAR3
      autophosphorylated itself in vitro on threonine residues. The expression of XAR4
      was found throughout embryogenesis, from oocytes to tailbud embryos, and also in
      adult tissues. By whole mount in situ hybridization, the XAR4 transcripts were
      detected in the animal half of blastulae and dorsally in gastrulae and neurulae.
      In tadpoles, the transcript was seen in the brain and around the otic vesicles.
      These results show that the activin type I receptor is expressed during Xenopus
      embryogenesis and suggest that the type I and II receptors are expressed together
      both temporally and spatially, supporting the idea that activin induces mesoderm
      in the embryo through activation of the two types of receptors.

PMID- 8561795
TI  - Formation of interstrand DNA cross-links by bis-(2-chloroethyl)sulfide (BCES): a
      possible cytotoxic mechanism in rat keratinocytes.
AB  - Interstrand cross-links in the DNA of epidermal basal keratinocytes may be
      responsible for cell death and consequent vesication in skin exposed to BCES. The
      formation of cross-links and cytotoxicity were compared when cells in primary
      monolayer cultures of rat epidermal keratinocytes, synchronized at the G1/S
      boundary or in the G1 phase of the cell cycle, were exposed to BCES. The dose
      responsive formation of cross-links, measured with an ethidium bromide
      fluorescence assay, was determined immediately after exposure of cells at either
      position of the cycle. At 24 hr post-exposure, the level of cross-links in cells
      exposed at the G1 phase showed had not decreased significantly and was still dose
      dependent. However, cells exposed in the G1 phase showed a major decrease in
      cross-links. Formation of interstrand DNA cross-links appears to be related to
      the mustard's cytotoxicity.

PMID- 8561796
TI  - Piperine impairs cytochrome P4501A1 activity by direct interaction with the
      enzyme and not by down regulation of CYP1A1 gene expression in the rat hepatoma
      5L cell line.
AB  - Modulation of benzo(a)pyrene (BP) metabolism and regulation of CYP1A1 gene
      expression by piperine in 5L cells in culture was studied. Treatment of cultures
      with 60 microM piperine for different time periods inhibited metabolism of BP by
      50% within 4-8 h. Piperine uptake in 5L cells attained saturation plateau at 8 h
      and this related with the maximal impairment of BP metabolism. Exposure of cell
      cultures to piperine for 24 h indicated activation of CYP1A1 gene transcription.
      There was a 10-fold increase in CYP1A1mRNA and an approximately 7-fold increase
      in arylhydrocarbon hydroxylase (AHH) activity, while treatment with benzanthacene
      (BA) increased CYP1A1mRNA by 86- and AHH by 56-fold. Combined treatment with BA
      plus piperine further increased CYP1A1mRNA contents by about 25%. The BA
      inducible AHH activity, however, registered a decrease of about 45%. Piperine
      neither destroyed CYP1A1-protein nor affected the total cellular protein
      contents. Exposure of cultures to 0.01 to 3.0 microM trans-7,8-dihydroxy-7,8
      dihydrobenzo(a)pyrene for 24 h reduced maximum cellular growth by about 50%.
      Piperine at 60 microM offered full protection against the diol cytotoxicity. The
      results, suggest that piperine mediated inhibition of the AHH activity and
      consequent suppression of the procarcinogen activation is the result of direct
      interaction of piperine with CYP1A1-protein and not because of down regulation of
      the CYP1A1 gene expression.

PMID- 8561797
TI  - Identification of human genes related to olfactory-specific CYP2G1.
AB  - CYP2G1, which is uniquely expressed in the olfactory mucosa of rats and rabbits,
      may have functions important for the olfactory chemosensory system. The aim of
      the present study is to determine whether CYP2G genes are present in the human
      genome. Several gene fragments were obtained by PCR amplification of human
      genomic DNA. One fragment, termed E7, which contained an open reading frame for
      44 amino acids, is highly homologous in deduced amino acid sequence to residues
      322-375 in rabbit or rat CYP2G1. Three other gene fragment, termed E7-8, H2Gp1
      and H2Gp2, respectively, were also obtained and found to have structural homology
      with coding sequences in the rat CYP2G1 gene. RNA-PCR analysis of human nasal RNA
      indicated that at least one CYP2G gene is transcribed. Southern blot analysis of
      human genomic DNA with use of cloned E7 or E7-8 as the probe indicated that more
      than one CYP2G-related gene may be present in the human genome. These results
      provide a basis for further characterization of the structure and function of the
      human CYP2G genes.

PMID- 8561798
TI  - CD36 is spatially associated with glycoprotein IIb-IIIa (alpha IIb beta 3) on the
      surface of resting platelets.
AB  - Platelet activation and aggregation induced by agonists such as thrombin are
      accompanied by the phosphorylation of several proteins on tyrosine. Such tyrosine
      phosphorylation is dependent upon activation and ligand engagement of the major
      integrin receptor on the surface of platelets, glycoprotein (GP) IIb-IIIa (alpha
      IIb beta 3), but how this is accomplished is not known. The only platelet
      membrane GP known to associated with non receptor tyrosine kinases is CD36 (GPIV)
      which forms associations with pp60Fyn, pp62Yes, and pp54/58Lyn, and antibodies
      directed against CD36 activate platelets in a process dependent upon GPIIb-IIIa.
      These and other data suggest a physical association between the two membrane GPs,
      IIb-IIIa and CD36. By the use of immunoprecipitation of lysates of platelets that
      have been surface labeled and chemically crosslinked we show here that CD36 and
      GPIIb-IIIa are spatially associated on the surface of resting platelets.

PMID- 8561799
TI  - T cell lymphoma in transgenic mice expressing the human Hsp70 gene.
AB  - In the course of studying the role of hsp70 in the differentiation of pancreatic
      beta cells, transgenic founder mice were generated with the human hsp70 gene
      fused to the human insulin gene promoter. One resulted in a transgenic line that
      consistently developed diabetes mellitus, but unexpectedly three other
      independent transgenic founders developed generalized malignant lymphoma within
      10 months after birth. Immunochemical and RT-PCR analyses revealed that the
      transgene was expressed in the lymphoma cells. Flow cytometric analyses revealed
      that the tumor was originated from T lymphocytes. Our results provide the first
      experimental evidence that hsp70 is involved in the tumorigenesis of T cells most
      likely through the blockage of apoptotic signals.

PMID- 8561800
TI  - cDNA cloning of a murine homologue of Drosophila single-minded, its mRNA
      expression in mouse development, and chromosome localization.
AB  - A combination of the RT-PCR method and subsequent screening of the cDNA library
      of mouse skeletal muscle with the cDNA isolated by RT-PCR used as a probe led to
      isolation of cDNAs encoding a polypeptide (mSim) with bHLH and PAS domains which
      show high similarity to the corresponding regions of Drosophila Sim, a master
      regulator in neurogenesis. Experiments using a GST-fusion protein demonstrated
      that mSim heterodimerizes with Arnt (Ah receptor nuclear translocator), even more
      efficiently than AhR (Ah receptor) does with Arnt. RNA blot analysis using RNAs
      from various tissues of mice indicated that mSim transcript is expressed in
      several limited tissues such as muscle, kidney and lung of adult animals.
      Distribution of mSim mRNA was always accompanied with that of Arnt. All the
      results suggest a regulatory role of mSim in partnership with Arnt. Chromosomal
      location of the mSim gene was determined by fluorescent in situ hybridization to
      be localized on the C3.3-C4 band of mouse chromosome 16 which is syntenic with
      the human chromosome 21q22 carrying the Down syndrome critical region, where a
      gene highly homologous to the Drosophila sim was localized. Whole mount in situ
      hybridization using a unique part of mSim cDNA sequence showed that mSim mRNA was
      expressed in the ventral diencephalon, branchial arches and limbs. These findings
      will provide an approach to the cause of the Down syndrome as well as the
      elucidation of the functional roles of mSim in animal development.

PMID- 8561801
TI  - Nuclear envelope acts as a calcium barrier in C6 glioma cells.
AB  - The temporal and spatial changes of intracellular free calcium ([Ca2+]i) within
      the cytosol and nucleis of C6 glioma cells have been investigated with laser
      confocal scanning microscopy to evaluate the current view that Ca2+ ions pass
      freely through nuclear pores by diffusion. Our results indicate that localized
      cytosolic Ca2+ release, which appeared as puffs, spread with an apparent
      diffusion rate of 0.35 +/- 0.07 microns/sec (n = 44). This release was followed
      by an immediate Ca2+ uptake at the resting stage. Following the treatment with
      thapsigargin, an inhibitor of microsomal Ca(2+)-ATPase, release of nuclear Ca2+
      from certain nuclear hot zones and nuclear envelope was obtained. Most of the
      nuclear Ca2+ released were confined to the nuclear boundary, but a slow migration
      of Ca2+ towards the cytosol was observed. The apparent diffusion rate of this
      Ca2+ release is 0.015 microns/sec. By contrast, the inward spread into nucleus
      occurred with a diffusion rate of 0.04 microns/sec. From these diffusion rates
      and other experimental evidence, we conclude that the movement of Ca2+ at the
      nucleocytosolic interface is more than a simple diffusion process and the
      interface is a barrier to Ca2+ movement.

PMID- 8561802
TI  - In situ identification of messenger RNA of endothelial type nitric oxide synthase
      in rat cardiac myocytes.
AB  - The endothelial type nitric oxide synthase (NOS) termed as NOS-III has been
      demonstrated in various nonendothelial cells. Although NOS-III was recently found
      in the cardiac tissues, identification of the cells expressing NOS-III gene in
      the heart remains unknown. In this study, we compared the expression of NOS-III
      mRNA in various tissues of rats by Northern blot analysis using a homologous cDNA
      probe and identified the cell type by in situ hybridization histochemistry with a
      cRNA probe. NOS-III mRNA was found more abundantly in atria and ventricle than in
      other various tissues examined. NOS-III mRNA was intensely and specifically
      visualized in the cardiac myocytes as well as in the endothelial cells of the
      heart. No staining was seen with a sense cRNA probe. These results provide the
      first in vivo evidence for NOS-III mRNA in the cardiac myocytes and suggest its
      role in the regulation of cardiac functions.

PMID- 8561803
TI  - Detection of ret homodimers in MEN 2A-associated pheochromocytomas.
AB  - Using transfection of NIH 3T3 cells, we have recently demonstrated that multiple
      endocrine neoplasia (MEN) 2A mutations activate the c-Ret protein by inducing its
      disulfide-linked homodimerization on the cell surface. To investigate whether the
      homodimers are present in original tumors, the expression of the c-Ret protein
      was analyzed in eight sporadic and two MEN 2A-associated pheochromocytomas, the
      latter two of which contained mutations in cysteine 618 or 634 of Ret. The c-Ret
      protein was expressed at variable levels in all pheochromocytomas examined. By
      labeling the c-Ret protein immunoprecipitated from tumor tissues with [gamma
      32P]ATP in vitro, its homodimers were detected in pheochromocytomas from MEN 2A
      patients but not in a sporadic tumor. This result represents the first
      demonstration of Ret homodimers in original tumors.

PMID- 8561804
TI  - Two families of murine carbohydrate ligands for E-selectin.
AB  - In search of endogenous oligosaccharide ligands for the endothelial adhesion
      molecule E-selectin in mouse, glycolipids from tissues and the neutrophilic cell
      line 32D c13 were tested for E-selectin binding. Kidneys of BALB/c and NMRI mice
      (but not CBA) and the 32D c13 cells were found to contain minor glycolipid
      populations that support strongly the binding of murine E-selectin. By
      chromatogram binding experiments and in situ liquid secondary ion mass
      spectrometry (LSIMS) with neoglycolipids derived from their endoglycoceramidase
      released oligosaccharides, in conjunction with compositional and linkage
      analyses, one of the glycolipid ligands in kidney was identified as the Le(x)
      active extended globo-glycolipid: [formula: see text] Neoglycolipids enriched for
      the ligand structures were obtained from oligosaccharides released by endo-beta
      galactosidase from the 32D c13 cells. By TLC-LSIMS and antibody binding, the main
      E-selectin binding determinant on these was identified as sialyl-Le(a).

PMID- 8561805
TI  - Spin trapping of O-, C-, and S-centered radicals and peroxynitrite by 2H
      imidazole-1-oxides.
AB  - Spin trapping with 2H-imidazole-1-oxides (2,2,4-trimethyl-2H-imidazole-1-oxide
      (TMIO); 4-carboxy-2,2-dimethyl-2H-imidazole-1-oxide, potassium salt (CDMIO); 2,2
      dimethyl-4-phenyl-2H-imidazole-1-oxide (DMPIO)) was studied. It was found that
      these compounds form spin adducts with different short lived free radicals, such
      as OH, CH3, CH2OH, CH3(CH)OH, C(CH3)3O, HOCH2CH2S, glutathionyl and cysteinyl
      radicals. 2H-imidazole-1-oxides did not trap superoxide radical. Therefore, the
      detection of OH and thiol radicals is not complicated by the presence of
      superoxide radical. It was shown that 2H-imidazole-1-oxides are effective
      scavengers of peroxynitrite forming the same spin adducts as with OH-radicals.
      Thus, TMIO, CDMIO and DMPIO can be used for spin trapping studies in chemical and
      biological systems.

PMID- 8561806
TI  - The porcine sperm motility inhibitor is identical to beta-microseminoprotein and
      is a competitive inhibitor of Na+,K(+)-ATPase.
AB  - We have isolated a small porcine seminal protein called SMI-1. Our results from
      peptide sequence, amino acid composition and mass spectral analyses reveal that
      SMI-1 is identical to porcine beta-microseminoprotein, a protein with unknown
      function. We also report here that this protein inhibits competitively the
      activity of Na+,K(+)-ATPase purified from porcine cerebral cortex in a dose
      dependent manner. The inhibitory effect could be reversed by the addition of ATP.
      The half-maximal inhibition was achieved at an inhibitor concentration of 90
      microM.

PMID- 8561807
TI  - Photoinactivation of trypanothione reductase and glutathione reductase by Al
      phthalocyanine tetrasulfonate and hematoporphyrin.
AB  - The irradiation of Trypanosoma congolense trypanothione reductase (TR), human
      erythrocyte (HGR) and yeast glutathione reductase (YGR) with visible light in the
      presence of Al-phthalocyanine tetrasulfonate (A1PcS4) or hematoporphyrine (Hp)
      caused a time-dependent inactivation of these enzymes. TR was inactivated more
      rapidly than either HGR or YGR. Half-maximal rates of inactivation were
      determined in the presence of 100 microM Hp and 1.4-17 microM AlPcS4. The
      photosensitized irradiation modified the disulfide substrate-binding sites of
      these enzymes, most likely the conserved catalytic histidine residue. In the
      dark, AlPcS4 acted as a reversible inhibitor competitive with the disulfide
      substrate of TR and HGR. These findings suggest the possible use of
      photosensitized irradiation for preventing the transmission of trypanosomiasis by
      blood transfusion.

PMID- 8561808
TI  - Regulation of the serum-activated Ca(2+)-dependent chloride channel in Xenopus
      oocytes.
AB  - Fetal bovine serum evoked Ca(2+)-dependent chloride currents with two components
      in Xenopus oocytes. The evoked currents were inhibited by GDP beta S, but not by
      pertussis toxin (PTX). An inositol 1,4,5-triphosphate (IP3) receptor antagonist,
      heparin completely inhibited the currents, although a phospholipase C inhibitor,
      neomycin had no effect. The serum-activated currents were enhanced to 171% by a
      selective protein kinase C (PKC) inhibitor, GF109203X. By contrast, a potent PKC
      activator, TPA, abolished the initial component of the currents and arachidonic
      acid enhanced this effect. The effects of TPA and/or arachidonic acid on the
      currents inhibited by GF109203X. These results indicate that the receptor for
      serum is linked to a PTX-insensitive G-protein involving cytosolic Ca2+ release
      through IP3 and PKC activation by a mechanism independent of a phospholipase C
      mediated phospholipid signaling. Furthermore, the evoked currents are regulated
      by PKC and arachidonic acid appears to potentiate its effect.

PMID- 8561809
TI  - Molecular cloning of a novel human melanocortin receptor.

PMID- 8561810
TI  - Collecting outcome data. Existing tools, preliminary data, future directions.
      Task Force on Treatment Outcome and Cost Effectiveness.

PMID- 8561811
TI  - PPOs: are they good for ASHA members? Task Force on Treatment Outcome and Cost
      Effectiveness.

PMID- 8561812
TI  - Audiology and the ethics of leadership.

PMID- 8561813
TI  - Speech-language pathology assistants. Support personnel or lower-level
      practitioners?

PMID- 8561814
TI  - Hyperacusis.

PMID- 8561815
TI  - [Diagnosis of endolymphatic hydrops with low tone masked otoacoustic emissions].
AB  - BACKGROUND: A new method of diagnosis of endolymphatic hydrops by recording low
      tone masked evoked otoacoustic emissions (TEOAE) is presented. METHODS: A short
      acoustic stimulus and a masker tone of 30 Hz are applied in an adjustable phase
      relation simultaneously to the same ear. In the normal hearing ear the masker
      shows little influence on the TEOAE at 0 degrees, whereas the suppression at
      phase 270 degrees (maximal rarefaction at the eardrum) is nearly complete.
      However, in cases of endolymphatic hydrops this masking effect is reduced or
      absent, indicating impaired mobility of the basilar membrane. RESULTS: The masked
      TEOAE were recorded of patients with normal hearing, Meniere's disease, and
      sudden hearing loss without vertigo. In Meniere cases with supposed endolymphatic
      hydrops, the amplitude modulation of the emissions was found to be much less than
      in the other groups. CONCLUSIONS: Where TEOAE can be recorded, low-tone masking
      is a quick, objective, and noninvasive method for the diagnosis of endolymphatic
      hydrops.

PMID- 8561816
TI  - [Early detection and hearing aid management of pediatric unilateral hearing
      loss].
AB  - BACKGROUND: Unilateral hearing loss in children is frequently an incidental
      diagnosis, usually late. As in binaural hearing disorders, early detection is
      extremely important to protect the function of the "remaining ear" and thus
      ensure acquisition of speech. Prompt initial probatory treatment with a
      conventional hearing aid is necessary to take advantage of the sensitive phases
      of development and maturation of the auditory pathways. This allows
      lateralisation as well as a better discrimination, avoiding cocktail party and
      non-physiologic head shadow effects. PATIENTS: The study includes 32 children
      with a conventional hearing aid. The average age of diagnosis was 5.5 years. The
      children were initially treated with a conventional hearing aid. RESULTS: The
      etiology remained unknown in the majority of the cases. Twenty-seven of the
      children were observed over a longer period, averaging 2 years. Hearing aid
      acceptance was found to be 63% with a measurable hearing improvement in 59% of
      the patients, even in the presence of severe hearing disorders. In the majority
      of the cases, the etiology remained unknown. CONCLUSION: More knowledge about
      risk factors for unilateral hearing losses in children should improve the chances
      for early detection, making hearing aid supply at a younger age possible. This
      should happen firstly in a probatory manner and in cases with hearing aid
      acceptance and a measurable hearing improvement definitely.

PMID- 8561817
TI  - [Basic principles for indications in phonosurgery].
AB  - BACKGROUND: Phonosurgery became an accepted surgical modality in the 1960s and
      refers to any surgery designed primarily for the improvement or restoration of
      voice. In a wider sense it also includes procedures involving the articulatory
      organs aiming at improvement of speech. Phonosurgery as "esthetic surgery" of the
      vocal organ differs clearly in its intentions from traditional laryngeal surgery
      which is performed because of vital indications. It is therefore necessary to
      define basic principles for the indication of phonosurgery. In this paper,
      general suggestions for the preconditions and importance of diagnostic criteria
      for the indication are given. PRECONDITIONS FOR INDICATION: 1. Diagnosis and
      documentation, 2. Patient's requests and needs, 3. Conservative therapeutic
      procedures or concept. RELEVANCE OF DIAGNOSTIC CRITERIA FOR INDICATION: 1.
      Audible findings, 2. Visible functional findings (stroboscopy), 3. Visible
      morphological findings. Phonosurgical interventions never should simply focus on
      the appearance of the vocal folds but on improving the patient's voice adapted to
      his or her individual requests and needs.

PMID- 8561818
TI  - [Carcinoma of the temporal bone--current diagnostic and therapeutic aspects].
AB  - BACKGROUND: Carcinoma of the external ear canal and the middle ear is a rather
      rare event and is especially seen in patients with chronic inflammatory ear
      disease. PATIENTS: Between 1993 and 1994, we treated seven patients with such a
      tumor, of which six proved to be a squamous cell carcinoma and one presumably
      adenocarcinoma. In three patients, the malignoma developed in a radical cavity of
      the ear and caused a facial palsy. Only two patients were without any discharge
      of the ear. Beside facial palsy, hemorrhagic otorrhea and otalgia were the
      leading symptoms. One patient presented with a bilateral painless swelling of the
      neck due to lymph node metastasis. Diagnosis was made by means of biopsy in only
      three patients and on the basis of a resected specimen after mastoidectomy in
      four patients. Angiography and computed tomography and magnetic resonance imaging
      studies were performed prior to treatment to determine the extent of the tumor.
      RESULTS: The tumor was resected by petrosectomy, parotidectomy, and neck
      dissection in 5 patients. Three times the margins of the histological specimen
      were free of tumor. Lymph node metastasis in the neck were seen in 5 cases, while
      distant metastasis did not occur. Two patients underwent primary irradiation, but
      a postoperative radiation therapy was performed five times. To date, three
      patients died after one year follow-up. CONCLUSIONS: Carcinoma of the temporal
      bone is a rare tumor, which can be treated only in case of early diagnosis.

PMID- 8561819
TI  - [Possible applications of brachytherapy from the viewpoint of the ENT physician].
AB  - BACKGROUND: Surgery, conventional radiation therapy, and chemotherapy are
      established methods of treating patients with head and neck cancer. Conventional
      radiation therapy is often ineffective in treating recurrent tumors. Modern
      methods of interstitial and intracavitary brachytherapy change this view. METHODS
      AND PATIENTS: In our series of 37 patients with recurrent head and neck cancer,
      we encountered no technical difficulties in placing indwelling catheters,
      needles, or applicators. We treated tumors of the nose, epipharynx, tongue, base
      of the tongue, trachea, esophagus, and cervical lymph nodes. In these patients,
      we successfully irradiated the tumor with doses up to 30 Gray. A case history is
      presented to demonstrate the combined action of intratumoral interferon alfa
      injection and interstitial brachytherapy on a tumor of the base of the tongue.
      RESULTS: Total remission rate 32/36 patients, 14 complete remission, 18 partial
      remission. Main complications were bleeding in one patient due to a vascular
      lesion and fistula formation. CONCLUSION: Brachytherapy is well suited for
      treating recurrent tumors of the head and neck region in individual patients.

PMID- 8561820
TI  - [Examinations with DNA cytometry of mouth and oropharyngeal lavage fluid as a
      screening method in diagnosis of malignancies of the mouth cavity and
      oropharynx].
AB  - BACKGROUND: Due to a high rate of false negative results, cytologic examinations
      of scrapings are currently not very common in diagnosing squamous cell carcinomas
      of the upper aerodigestive tract. The purpose of the present study was to
      determine whether cytometric and cytologic examinations are suitable in
      diagnosing squamous cell carcinomas of the oral cavity and oropharynx. METHODS:
      Cytologic and cytometric examinations of rinsing fluid from the mouth and throat
      were performed in 14 patients with histologically confirmed squamous cell
      carcinomas of the oral cavity and oropharynx. The patients were asked to rinse
      their mouth and throat with 10 ml of Ringer's solution. The rinsing fluid was
      centrifuged and fixed. The sediment was then smeared onto glass slides and
      stained according to the technique of Feulgen. Quantitative DNA measurements were
      then performed using a TV-based image analysis system. The DNA indices, 2 c DI, 5
      c EE, and DNA entropy were determined from the single-cell measurements. RESULTS:
      The results of the carcinoma patient group were compared to those obtained in 19
      patients without any evidence of cancer (control group). With this method,
      malignant and benign cells could be distinguished in all cases, i.e., all
      patients with a carcinoma could be identified as positive by this examination,
      whereas patients without evidence of cancer were identified as negative in all
      cases. CONCLUSIONS: The results of this pilot study show that quantitative DNA
      measurements might be a suitable tool for non-invasive screening of patients who
      are at high risk for developing a carcinoma in the upper aerodigestive tract and
      for follow-up of patients in order to detect tumor recurrence after successful
      initial treatment.

PMID- 8561821
TI  - [Establishment and characterization of 2 cell lines of squamous epithelial
      carcinoma of the mouth floor and tongue].
AB  - OBJECTIVE: The cultivation of squamous cell carcinoma cells of the upper
      aerodigestive tract is more difficult compared to other malignancies because of
      microbial contamination. The establishment of new squamous cell carcinoma cell
      lines is absolutely necessary to further characterize this tumor entity. METHODS:
      Two squamous cell carcinoma cell lines of the floor of the mouth and the tongue
      were established from tumor biopsies. They were examined by light and electron
      microscopy. Furthermore immunocytochemical and DNA cytofluorometric studies were
      performed. The growth features were tested in a tumor-stem cell assay and through
      transplantation in thymusless nude mice. RESULTS: The epithelial character of the
      cells was determined morphologically, immunocytochemically, and immunologically.
      Both cell lines shaved an aneuploid DNA Index of 1.92 for the tongue carcinoma
      cell line (HCTK-1) and 1.77 for the floor of the mouth cell line (HCFMK-1). The
      plating efficiency was 0.008 and 0.01%. Cell differentiation in the original
      tumor and the nude mice tumor was identical. HCTK-1 is in the 25th passage and
      HCFMK-1 in the 42nd. CONCLUSIONS: The two new squamous cell carcinoma cell lines
      HCFMK-1 and HCTK-1 may serve as a basis for various in vitro investigations and
      may help to further characterize squamous cell carcinomas of the upper
      aerodigestive tract.

PMID- 8561822
TI  - [Initial results of glutathione-S-transferase GSTM1 and GSTT1 genotypes and
      genetic predisposition for laryngeal carcinoma].
AB  - BACKGROUND: While cigarette smoking and alcohol consumption have been linked to
      laryngeal carcinoma, the role of genetic factors in determining individual
      susceptibility is unknown. We describe the role of allelism at glutathione-S
      transferase GSTM1, GSTT1, and cytochrome P 450 CYP2D6 loci in determining
      individual susceptibility to laryngeal squamous cell carcinoma. METHODS: Enzyme
      genotypes were determined using the polymerase chain reaction in 169 patients
      suffering T1-T4 laryngeal carcinoma and in 145 controls. RESULTS: While the
      frequency of the heterozygote GSTM1 A/B genotype was statistically significantly
      lower in the cases than controls, the frequency of the GSTT1 null genotype was
      higher in cases than controls. CONCLUSION: These initial data suggest that
      allelism at GST loci mediates susceptibility to squamous cell carcinoma of the
      larynx. Thus, GSTM1 A/B appears to be associated with a reduced risk while GSTT1
      null confers increased risk. The findings are compatible with the view that
      genetic predisposition is important in determining risk of this cancer.

PMID- 8561823
TI  - [Tissue engineering: artificial tissue replacement containing vital components].
AB  - Tissue engineering as a new field of research has gained increasing importance in
      recent years. The interdisciplinary field combines, biomaterials cell biology,
      and cell culture bio-engineering technology. The main focus of tissue engineering
      is the synthesis of artificial constructs or tissues based on vital cells or cell
      matrix. Biomaterials provide a three-dimensional structure to shape or guide
      tissue development. Isolated cartilage cells from a patient can form new tissues
      when suspended in non-woven resorbable polymers for reconstructive surgery. To
      achieve sufficient amounts of autologous cells for transplant formation, cells
      from biopsies have to be multiplied in monolayer culture. Dedifferentiated and
      undifferentiated mesenchymal cells may be used for bone and cartilage
      engineering. High cell densities in three-dimensional cultures require perfusion
      techniques to stabilize culture conditions. Morphogenetic factors such as BMP
      (bone morphogenetic protein) are thought to play a key role in inducing and
      controlling phenotypic tissue formation. In conclusion, modern in vitro
      approaches open new avenues for the development of vital tissue replacements for
      the clinic. Tissues can be repaired with the patient's own cells eventually
      leaving no residual artificial materials. Tissue engineering further provides new
      approaches for in vitro models of the extracellular matrix or diseases which
      mainly affect this matrix such as rheumatoid arthritis or osteoarthritis. This
      article describes recent developments in connective tissue engineering and
      discusses the potential for human tissue repair and reconstructive surgery.

PMID- 8561824
TI  - [Case report: swallowed hearing aid].
AB  - An 86-year-old man presented ambulatory with acute dysphagia. Radiologic
      examination and endoscopy revealed a swallowed postauricular hearing aid. The
      earmold of the hearing aid became visible in the hypopharynx after mucus and
      saliva were removed. It could be extracted without effort once the connecting
      tube was disconnected from the coupling device lodged in the upper esophageal
      sphincter. The hearing aid itself was impacted in the proximal esophagus and was
      extracted without any problems. The postoperative phase was uneventful with
      normal swallowing and discharge. Technical inspection revealed that the hearing
      aid no longer worked. Diffusion of toxic substances (zinc, mercury) from the
      impacted batteries is not to be expected.

PMID- 8561825
TI  - [Langerhans cell histiocytosis of the temporal bone].
AB  - BACKGROUND: The localized form of the Langerhans cell histiocytosis was referred
      to earlier as eosinophilic granuloma, which has the best prognosis of all
      histiocytosis syndromes concerning survival. The non-malignant proliferative
      disorder of the histiocytic system is still of unknown etiology. Characteristic
      radiographic signs are osteolytic lesions. PATIENT: We report on an otologic
      manifestation of a 20-year-old man's temporal bone, which developed three years
      after a successful treatment of an eosinophilic granuloma of the mandible.
      RESULTS: Surgery and low-dose irradiation led to a complete remission of the
      disease. Other manifestations of the disease were not detected until now.
      CONCLUSIONS: In the presence of chronic aural discharge, Langerhans cell
      histiocytosis must bei considered in differential diagnosis and a
      histopathological examination should be performed.

PMID- 8561826
TI  - [From otoscope to ophthalmoscope and back. The interwoven history of their
      invention and introduction into medical practice. Pictures from the history of
      otorhinolaryngology, illustrated by instruments from the collection of the
      Ingolstadt German Medical History Museum].
AB  - Friedrich Hofmann, medical officer in Burgsteinfurt, Westphalia, Germany, in 1841
      described a concave mirror with a central aperture in it as the ideal instrument
      that allowed reflecting and focussing light into the external auditory canal and
      simultaneously inspecting the tympanic membrane without obstructing either the
      light or the view. He recommended his device also for the inspection of other
      concealed regions of the body. His invention was referred to by Martell Frank in
      his textbook of otology in 1845, but otherwise attracted no attention. Hermann
      Helmholtz, physiologist in Konigsberg, East Prussia, devised his ophthalmoscope
      in 1850-51 in order to study the phenomenon of glowing eyes. With this instrument
      he was the first to see the retina of a living human. As means of illumination he
      used small panes of glass similar to cover-glasses which were introduced into the
      common visual axis of the observer and the subject at such an angle that light
      from a lamp was reflected into the subject's eye while the observer inspected the
      subject's retina through the glass and an appropriate lens. He recommended this
      type of illumination also for otoscopy. His invention was at once acclaimed
      throughout the world and opened completely new opportunities in ophthalmology.
      The slanting panes of glass, however, were not the ideal solution for
      illumination. It was only one year later that Ruete in Gottingen replaced them
      with a concave mirror with a central aperture, and there is every indication that
      Frank's report on Hofmann's mirror had suggested this technique to him. During
      the following two years quite a number of other modifications of the
      ophthalmoscope were constructed, all of them using the concave mirror with a
      central aperture, which soon became synonymous with the ophthalmoscope as such.
      Von Troltsch, otologist and ophthalmologist in Wurzburg, presented a concave
      mirror with a central aperture for otoscopy in Paris in 1855-56. His instrument
      was obviously derived from the already well known ophthalmoscope by adapting the
      diameter and focal distance to this special application. His primary concern was
      to use daylight instead of artificial light for otoscopy. Von Troltsch did not
      know Hofmann's publication, but later did not hesitate to acknowledge Hofmann's
      priority. It was von Troltsch who popularized the concave reflector with a
      central aperture as the instrument of choice in otoscopy, and subsequently also
      for rhinoscopy and laryngoscopy. Further modifications were devised to have the
      hands free for operations. Thus the reflector was fixed to the forehead by strap
      and buckle or a vulcanite band, or it was provided with a handle that was to be
      held between the teeth, or it was attached to a spectacle frame. The details of
      this interwoven history are related and highlighted by numerous quotations and
      historical illustrations.

PMID- 8561827
TI  - Interaction of organophosphorus insecticide methylparathion with calf thymus DNA
      and a synthetic DNA duplex.
AB  - The interaction of an organophosphorus insecticide methylparathion (O,O-dimethyl
      O-4-nitrophenyl phosphorothioate) with double-stranded DNA was characterized by
      UV and circular dichroism (CD) spectroscopy. Two kinds of DNA were employed: calf
      thymus DNA (CT DNA) and a synthetic two-stranded oligomer of sequence 5'
      d(TTGGATCCGAATTCAAGCTT)-3'. Melting curves and CD spectra were taken for the DNAs
      in the presence of the insecticide at methylparathion/DNA base pair molar ratio
      of 0.5. The insecticide evoked a decrease of the melting temperature and a
      broadening of the transition range for CT DNA. Similar effects were observed for
      the synthetic oligomer but they were less pronounced than in the case of CT DNA.
      Methylparathion evoked a slight shift and an increase in the amplitude of the
      negative band in the CD spectra of both DNAs. Obtained results indicate that
      methylparathion may perturb the thermal stability and conformation of DNA, which
      is an evidence that the insecticide has an ability to interact directly with DNA.

PMID- 8561828
TI  - Glycerol inhibits or uncouples the plasma membrane (Ca(2+)+Mg2+)ATPase of kidney
      proximal tubules depending on the Ca2+ concentration.
AB  - In this report it is shown that glycerol (0.5-10% v/v) stimulate the C12-E9
      solubilized renal (Ca(2+)+Mg2+)ATPase in the presence of low concentrations of
      free Ca2+ (< 10(-6) M). At 4% (v/v), the polyol decreases the K0.5 for Ca2+ from
      1.15 to 0.22 microM at the high-affinity site, and a very-high-affinity Ca2+
      component appears. This component has a K0.5 < or = 10(-9) M and its maximal
      velocity is about one-third that of the fully activated enzyme (at 10-20 microM
      Ca2+), which is not affected by glycerol (21.1 and 20.2 nmollmg-1.min-1 in the
      absence and presence of the polyol, respectively). The low-affinity, inhibitory
      component of the Ca2+ curve (50-1000 microM) is also unaffected by glycerol. With
      0.07 microM free Ca2+ and soluble enzyme, the stimulatory effect of glycerol
      saturates at approximately 10% (v/v). In contrast, with 17 microM free Ca2+,
      glycerol has little effect up to 10% (v/v), and then progressively inhibits
      ATPase activity. These data indicate that the effect of the polyol is modulated
      by the occupancy of the high-affinity Ca2+ sites. In native vesicles, the
      stimulation promoted by low concentrations of glycerol at low concentrations of
      Ca2+ is accompanied by inhibition of active Ca2+ transport, indicating that, in
      these conditions, the polyol uncouples ATPase activity and ATP-driven Ca2+
      influx.

PMID- 8561829
TI  - Quantification of ecdysteroids by immunoassay: comparison of enzyme immunoassay
      and radioimmunoassay.
AB  - The performance of enzyme immunoassay (EIA) and radioimmunoassay (RIA) in the
      quantitative analysis of ecdysteroids was compared. The EIA was found to be at
      least equivalent to the RIA with respect to analytical range and sensitivity and
      to be more comfortable with respect to safety and time saving. When biological
      samples were analyzed by both assays a good correlation (r = 0.83) was found.
      Since the EIA has certain advantages over the RIA, we now recommend the use of
      the former assay for the quantification of ecdysteroids.

PMID- 8561830
TI  - Phylogeny of Old and New World vultures (Aves: Accipitridae and Cathartidae)
      inferred from nucleotide sequences of the mitochondrial cytochrome b gene.
AB  - The molecular phylogeny of 11 Old World and 5 New World vultures was inferred
      from nucleotide sequences of the mitochondrial cytochrome b (cyt b) gene.
      According to this analysis carrion-feeding has evolved independently at least
      three times during evolution: 1.) In the New World vultures, which are clearly
      separated from vultures of the family Accipitridae; 2.) in the Neophron-Gypaetus
      clade which is positioned at the base of the Accipitrid tree and 3.) in the Gyps
      Aegypius-complex which encloses the largest group of Old World vultures. Thus the
      genetic data clearly show that the carrion-feeding lifestyles and associated
      morphologies shared by New and Old World vultures are rather based on convergence
      than on close genetic relatedness. Employing the cyt b sequences of 12 other
      members of the Falconiformes and 10 members of the Ciconiiformes (sensu Sibley
      and Monroe, 1990) the phylogenetic relationship between the three clades of
      vultures and these other taxa was assessed. New World Vultures appear to share
      distant ancestry with storks but a close relationship is unlikely.

PMID- 8561831
TI  - [Selection and mutation from the theoretical information point of view--limits of
      the preservation of genetic information].
AB  - There is no doubt that evolution can only operate in accordance with the laws of
      thermodynamics. To transform this simple perception into a statement that can be
      quantified it is necessary to examine how the entropy (or the information
      content) changes by means of the two main factors of evolution: selection and
      mutation. In the present paper this aim was reached by using the methods of
      information theory. That evolution becomes possible the change of information by
      mutation and selection must not be negative in the long run. Consequently an
      upper limit for the information content of the genome must be assumed. If the
      evolution as a self-optimizing process gains this upper limit it reaches a
      dynamic equilibrium at which the increase of entropy by mutation balances the
      decrease of entropy by selection. In particular it was examined under which
      circumstances of dynamic equilibrium master-genotypes (genotypes that can
      preserve their specific sequence over a long time) can exist.

PMID- 8561832
TI  - Geographically overlapping Alzheimer's disease registries: comparisons and
      implications.
AB  - In the medical and epidemiologic literature, a registry denotes a data base in
      which registrants share some common characteristic such as disease category. One
      criticism of registries is that they frequently collect subjects in a haphazard
      fashion and, hence, are "nonrepresentative of the population purportedly being
      represented." In this report, we compare two registries: an incident-based
      Alzheimer's Disease Patient Registry (ADPR) recruiting subjects for epidemiologic
      studies from a large health maintenance organization; and an Alzheimer's Disease
      Research Center (ADRC) registry recruiting subjects for phenomenologic, biologic,
      and pharmacologic studies. While these registries share personnel, overlap
      geographically, and use similar diagnostic procedures, they differ substantially
      in their missions and resulting recruitment strategies. We compared these
      registries with respect to demographic characteristics and cognitive features at
      subject entry. Subjects enrolled in the incident-based registry are older and
      report shorter time between symptom onset and recruitment. They are less demented
      and mirror the general population demographically more closely than do subjects
      in the other registry. The ADRC registry contains a much greater proportion of
      subjects with higher educational attainment.

PMID- 8561833
TI  - Graphomotor perseveration and wandering in Alzheimer's disease.
AB  - Perseveration, spatial orientation, and attention/concentration were assessed in
      15 patients with a probable diagnosis of senile dementia of the Alzheimer's type.
      Subjects were divided into two groups, wanderers and nonwanderers, based on
      caregiver ratings using a modified version of the Caregiver Checklist. Graphic
      productions of wanderers on the Bender Visual Motor Gestalt Test and Clock
      Drawing Test displayed greater total perseveration and more recurrent and
      continuous perseverations than those of nonwanderers. Spatial orientation and
      attention/concentration were similar between groups. These preliminary results
      suggest that graphomotor perseverations exhibited during the mild to moderate
      stages may serve as a marker for wandering in Alzheimer's disease.

PMID- 8561834
TI  - Behavioral disturbance in dementia.
AB  - Fifty-seven subjects with moderate to severe dementia (49 with Alzheimer's
      disease) were rated twice, 8 weeks apart, using the Mini-Mental State Examination
      (MMSE), the Blessed Information-Memory-Concentration Test (BIMC), and the
      Stockton Geriatric Rating Scale (SGRC). Only three subjects lived at home; the
      rest were in long-stay hospital beds or nursing homes. For 29 subjects, the first
      rating coincided with their referral to a comprehensive geriatric psychiatry
      service. The main hypothesis, that the level of behavioral disturbance would
      correlate positively with the level of cognitive impairment, was strongly
      confirmed. This finding may reflect the severity of dementia in the study sample.
      The correlations between MMSE and BIMC scores were .87 at entry and .92 at exit,
      suggesting that the two measures were broadly equivalent, although both had
      marked floor effects. Test-retest reliability was high for all three measures.
      Overall, medication was of limited effectiveness in managing severe behavioral
      disturbance, highlighting the need for introducing effective behavioral programs.

PMID- 8561835
TI  - ERP indices and neuropsychological performance as predictors of functional
      outcome in dementia.
AB  - We compared the relative value of neuropsychological and event-related potentials
      (ERPs) obtained during both passive and active auditory oddball paradigm measures
      for determining functional outcome in dementia 4 years following initial
      assessment. Functional outcome was assessed by structured interview of family
      members of 29 patients with dementia, and patients' functional status was rated
      in seven areas: mortality, incontinence, institutionalization, ADL dependence,
      verbal responsiveness, recognition of family members, and capacity for social
      interaction. A total functional outcome score (ADLTOTAL) was obtained by summing
      across these individual outcome measures. Many of the neuropsychological measures
      correlated strongly with overall functional outcome, whereas P3 amplitude and
      latency on the active ERP condition were the only ERP indices to predict
      functional outcome. When ERP and neuropsychological measures were considered
      simultaneously using stepwise multiple regression analyses, the
      neuropsychological measures were better predictors of most functional outcomes,
      although P3 latency was the best predictor of mortality. However,
      neuropsychological performance and ERPs appear to be sensitive to different
      functional outcomes. Therefore, evaluation of both ERPs and neuropsychological
      performance may ultimately have prognostic utility in the assessment of patients
      with dementia.

PMID- 8561836
TI  - Evaluation of cycloserine in the treatment of Alzheimer's disease.
AB  - This multicenter study evaluated the efficacy and safety of cycloserine and
      measured its effects on explicit and implicit memory tests in patients with
      Alzheimer's disease (AD). Four hundred ten patients with AD, aged 50 years or
      older, were enrolled in this parallel-group, double-blind, placebo-controlled,
      randomized trial of 5, 15, or 50 mg cycloserine or placebo twice daily, and 403
      entered the double-blind treatment phase. Two hundred sixty-five patients
      completed the entire 26-week treatment phase. There were no baseline differences
      among the four treatment groups. Cognitive Drug Research (CDR) efficacy
      assessments showed no differences between active treatments and placebo from
      baseline to study weeks 2, 6, 14, or 26. Patients receiving 15 mg of cycloserine
      improved significantly on one section of an implicit memory test. No differences
      among treatments were observed for any other assessment scales evaluated. The
      incidence and severity of adverse events were similar across treatment groups.
      Cycloserine was well tolerated but did not demonstrate consistent evidence of
      efficacy during the course of therapy. Higher doses may be necessary to achieve
      efficacy in the AD population and do not appear to be precluded by the adverse
      event profile seen in this study.

PMID- 8561837
TI  - Parkinsonism associated with fluoxetine and cimetidine: a case report.
AB  - Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) are
      effective for the treatment of depression in the elderly and offer a safer side
      effect profile as compared to tricyclics and monoamine oxidase inhibitors. We
      report a case in which a patient treated with fluoxetine developed parkinsonism
      following the introduction of cimetidine. Inhibition of hepatic P450 cytochrome
      enzymes by cimetidine with an increase in serum levels of norfluoxetine may have
      precipitated this extrapyramidal syndrome, which has been related to agonism of
      the serotonergic input to nigrostriatal tracts and basal ganglia. Parkinsonism as
      a side effect of SSRIs occurs infrequently, suggesting an idiosyncratic response
      resulting from a functional imbalance of serotonergic and dopaminergic activity
      in susceptible individuals. Careful monitoring of geriatric patients treated with
      fluoxetine is indicated, particularly for those on high doses, those with
      impaired hepatic functioning, or those treated with concurrent medications that
      slow the metabolism of fluoxetine.

PMID- 8561838
TI  - Tolerability of divalproex sodium in elderly psychiatric patients with mixed
      diagnoses.
AB  - This study addresses the tolerability of divalproex sodium in elderly psychiatric
      inpatients with various Axis I diagnoses, using structured assessments. A chart
      review for a 7-month period on a geropsychiatry inpatient unit identified 13
      patients who had been treated with divalproex sodium. All 13 patients received
      standardized ratings on the Cohen-Mansfield Agitation Inventory (CMAI), Brief
      Psychiatric Rating Scale (BPRS), Rating Scale for Side Effects (RSSE), and Mini
      Mental State Examination (MMSE) on admission and discharge, which were compared
      using paired t-tests for 12 of the 13 patients. The thirteenth patient was
      withdrawn from valproate prior to discharge after developing a delirium thought
      to be secondary to a divalproex-phenytoin interaction. All of the remaining 12
      patients tolerated divalproex sodium well with no significant change in MMSE
      scores (P = .486), CMAI scores (P = .0546), or RSSE scores (P = .124). The change
      in BPRS score was found to be significant (P = .004). Based on the present study
      and previously reported case series, divalproex sodium appears to be well
      tolerated in an elderly psychiatric population.

PMID- 8561839
TI  - Reliability of the Blessed Telephone Information-Memory-Concentration Test.
AB  - In-person cognitive evaluations can be costly and labor intensive in
      geographically widespread populations. Reliable telephone instruments that screen
      for cognitive status would greatly facilitate epidemiologic and other
      longitudinal studies. We evaluated the reliability of the Blessed Information
      Memory-Concentration (IMC) test when administered by telephone. Eighty-four
      subjects with a wide range of cognitive abilities were administered the Blessed
      IMC twice over a 3-week interval. Forty-nine of the subjects were administered
      the test both by telephone and in-person, and 35 of the subjects were tested
      twice by telephone. Spearman's rank correlation was used to compare scores of the
      different administrations (.96; P < .001) and to examine test-retest reliability
      (.96; P < .001). The Blessed Telephone IMC (TIMC) test exhibits excellent
      reliability both when compared to in-person administration as well as in test
      retest results. The Blessed TIMC appears to be a practical instrument for
      population and longitudinal studies when in-person assessment is not feasible.

PMID- 8561840
TI  - Neuroleptic treatment of agitation and psychosis in dementia.
AB  - Neuroleptics remain the mainstay for the treatment of behavioral disturbance and
      psychotic symptoms in demented patients. The limited available data suggest that
      low-dose neuroleptics are significantly more efficacious than placebo, though the
      magnitude of the effect is moderate in most published studies. Demented patients
      are particularly prone to neuroleptic side effects, and individualized dose
      titration may be necessary to achieve the optimal trade-off between efficacy and
      side effects. Target behavioral symptoms and side effects, including effects on
      cognition and activities of daily life, should be identified and assessed
      serially during neuroleptic treatment. The choice of neuroleptic depends more on
      likely side effects than differential efficacy, and non-response or intolerable
      side effects should lead to dose adjustment or a switch to an alternative class
      of neuroleptic (or an alternative type of medication). Further studies of optimal
      neuroleptic dosage, the optimal duration of continuation neuroleptic treatment,
      and placebo-controlled studies comparing neuroleptics to other classes of
      medications are needed.

PMID- 8561841
TI  - Biologic markers and neurochemical correlates of agitation and psychosis in
      dementia.
AB  - Behavioral and psychiatric symptoms frequently accompany the cognitive
      deterioration of dementia occurring in up to 80% of both community-based and
      nursing home patients. In Alzheimer's disease (AD), behavioral complications may
      develop at any stage of the disease process and tend to follow a more
      unpredictable course than the core cognitive symptoms. Over the past 15 years,
      our knowledge of the biologic and neurochemical basis of dementia, and of AD in
      particular, has increased significantly. Great emphasis has been placed on the
      cholinergic system abnormalities in the context of the cognitive impairment in AD
      and on the psychopharmalogic enhancement of cholinergic transmission in AD.
      However deficits in other neurotransmitter systems, such as the noradrenergic,
      serotonergic, and dopaminergic systems, also occur and may contribute to the core
      cognitive symptoms of AD. More recently, there has been increased interest in the
      biologic and neurochemical basis of behavioral and psychiatric disturbances in
      dementia. This article reviews the evidence for biologic and neurochemical
      correlates of psychosis and agitation in dementia, and discusses the treatment
      implications for these findings.

PMID- 8561842
TI  - Anticonvulsant and other non-neuroleptic treatment of agitation in dementia.
AB  - Studies have shown that the vast majority of patients with dementia experience
      some psychopathologic symptoms during the course of their illness. Symptoms of
      this nature, which can include frightening hallucinations or anxiety of phobic
      proportions, are subjectively distressing and can lead both to unsafe or violent
      situations as well as to the preventable use of inappropriate medication,
      physical restraint, and frequently to institutionalization. These
      psychopathologic manifestations of dementia often prove to be a burden on family,
      caregivers, and the health care system as well. This article presents an overview
      of the assessment and management of agitation as it relates to the severity of
      dementia symptoms and cognitive deterioration. Specifically, the use of
      anticonvulsant and other non-neuroleptic therapies is examined.

PMID- 8561843
TI  - The depressions of Alzheimer's disease: sorting, pharmacotherapy, and clinical
      advice.
AB  - Research describing wide prevalence variation of Alzheimer's disease (AD) and
      comorbid depression is explained in light of subsyndromal depressions, the use of
      standardized diagnostic instruments and procedures, and the subcortical and
      cortical components of mood. There appear to be several "depressions" of AD.
      Against this backdrop, double-blind, placebo-controlled studies of antidepressant
      use in AD are reviewed and methodologic problems identified. Evidence for
      efficacy in controlled trials is weak, but open-label trials are, as expected,
      more encouraging. The potential efficacy of new agents for the depressions of AD
      receive comment. A heuristic model makes use of the conclusions developed, the
      stage of illness, and a preliminary classification scheme for the depressions of
      AD; this model provides a rational basis for thinking about medication selection
      for AD depressions. Clinical decisions are illustrated.

PMID- 8561844
TI  - Methodologic issues regarding outcome measures for clinical drug trials of
      psychiatric complications in dementia.
AB  - Selecting outcome measures that are both psychometrically sound and sensitive to
      change is a very important aspect of clinical outcome research. A variety of
      measures have been introduced in recent years to assess behavioral complications
      in dementia, but few have been adequately tested in clinical trials. This article
      provides a discussion of factors to consider in selecting measures, including
      psychometrics, item content, assessment source, and sensitivity to change. A
      review of behavioral and psychiatric measures for dementia patients is provided,
      including measures of general behavioral disturbance, and measures specifically
      developed for agitation and depression. Each measure's psychometric
      characteristics, prior use with demented patients, and strengths and weaknesses
      with regard to treatment outcome research is summarized. The importance of
      linking measures to the investigators' hypotheses is discussed, along with
      recommendations for evaluating and selecting outcome measures depending on the
      needs of the specific investigation.

PMID- 8561845
TI  - Two-domain hemoglobin from the blood clam, Barbatia lima. The cDNA-derived amino
      acid sequence.
AB  - The blood clam, Barbatia lima, from Kochi, Japan, expresses a tetrameric (alpha 2
      beta 2) and a polymeric hemoglobin in erythrocytes. The latter hemoglobin is
      composed of unusual 34-kDa hemoglobin with a two-domain structure, and its
      molecular mass (about 430 kDa) is exceptionally large for an intracellular
      hemoglobin. The 3' and 5' parts of the cDNA of B. lima two-domain globin have
      been amplified separately by polymerase chain reaction and the complete
      nucleotide sequence of 1147 bp was determined. The open reading frame is 930
      nucleotides in length and encodes a protein with 309 amino acid residues, of
      which 73 amino acids were identified directly by protein sequencing. The mature
      protein begins with the acetylated Ser, and thus the N-terminus Met is cleaved.
      The molecular mass for the protein was calculated to the 35,244 Da. The cDNA
      derived amino acid sequence of B. lima two-domain globin shows 89% homology with
      that of two-domain globin from B. reeveana, a North American species. The
      sequence homology between the two domains is 75%, suggesting that the two-domain
      globin resulted from the gene duplication of an ancestral 17-kDa globin.

PMID- 8561846
TI  - ELISA quantitation of apolipoproteins in plasma lipoprotein fractions: ApoE in
      ApoB-containing lipoproteins (Lp B:E) and ApoB in ApoE-containing lipoproteins
      (Lp E:B).
AB  - Growing clinical evidence suggests that metabolic behavior and atherogenic
      potential vary within lipoprotein subclasses that can be defined by
      apolipoprotein variation. Variant constituency of apolipoproteins B and E (apoB
      and apoE) may be particularly important because of the central roles of these
      apolipoproteins in the endogenous lipid delivery cascade. ApoB is the sole
      protein of low-density lipoprotein (LDL), and like LDL cholesterol, the plasma
      apoB level has been positively correlated with risk for atherosclerotic disease.
      ApoE is a major functional lipoprotein in the triglyceride-rich lipoproteins, and
      may be crucial in the conversion of very low density lipoprotein (VLDL) to LDL.
      Based on work by others that enabled the quantititation of apoB-containing
      particles by content of up to two other types of apolipoprotein, we have
      developed a method for determining the amount of apoE in apoB-containing
      lipoproteins (Lp B:E) and the amount of apoB in apoE-containing lipoproteins (Lp
      E:B). From the Lp B:E and Lp E:B concentrations, the molar ratio of apoE to apoB
      in lipoproteins containing apoB and/or apoE in plasma can be determined. The
      methodology is fast, specific, and sensitive and should prove extremely useful in
      further categorizing lipoproteins and characterizing their behavior. In applying
      this method to clinical groupings of normo- and hyperlipidemia, we found that the
      plasma triglyceride level correlated with the apoE and Lp B:E concentrations in
      plasma, while the total cholesterol level correlated with the apoB and Lp E:B
      levels.

PMID- 8561847
TI  - Matrilysin: expression, purification, and characterization.
AB  - The expression vector pGEX-2T under the control of the IPTG-inducible tac
      promotor is effective for the production of a fusion protein of glutathione
      transferase (GST, 26 kDa) and promatrilysin (28 kDa) separated from the C
      terminus of GST by a thrombin cleavage site. Zwittergen (palmityl sulfobetaine),
      2%, solubilizes the fusion protein that is found associated with inclusion
      bodies. The solubilized fusion protein is purified by affinity chromatography on
      GSH agarose. Promatrilysin is obtained by thrombin cleavage either on the column
      or after GSH elution of the fusion protein. Mono S chromatography of the
      recovered protein yields homogeneous promatrilysin. The zinc content of
      promatrilysin and its activated enzyme product is slightly greater than 2 mol of
      zinc per mole of protein. The results indicate that the matrix metalloproteinases
      (MMPs) contain two metal-binding sites at which zinc is firmly bound and possibly
      a third site at which it is weakly bound. Primary sequence alignments for all the
      MMPs have a sequence homologous to the zinc-binding site of astacin, HExxHxxGxxH,
      suggesting one of the zinc sites is a catalytic one, in agreement with the known
      inhibition of these enzymes by chelators. However, the other zinc-binding site(s)
      likely reflect the different ways that astacin and the MMP subfamilies are
      stabilized, i.e., disulfides in astacin and metal ions in the MMPs.

PMID- 8561848
TI  - An improved method for large-scale purification of recombinant human glucagon.
AB  - Glucagon was expressed in Escherichia coli as a fusion protein including the
      glucagon sequence [Ishizaki et al. (1992), Appl. Microbiol. Biotechnol. 36, 483
      486]. The high-level expression of a protein in E. coli often results in an
      insoluble aggregate called an inclusion body containing a fusion protein. In our
      previous report [Yoshikawa et al. (1992), J. Protein Chem. 11, 517-525], we
      solubilized this inclusion body by using guanidinium chloride. However, the
      existence of denaturant caused problems such as a low proteolytic activity for
      transforming the fusion protein into glucagon and complicated purification
      methods. We tried to improve the method to enable large-scale purification. At
      alkaline pH, the inclusion body could be solubilized to a high concentration and
      cleaved by amino acid-specific endopeptidases. By utilizing isoelectric
      precipitations as a new economical purification method for glucagon from
      intermediates, the glucagon obtained was shown to be over 99.5% pure by
      analytical RP-HPLC. The yield was almost equal that of our previous method, and
      the glucagon produced was chemically and biochemically equivalent to natural
      glucagon.

PMID- 8561849
TI  - Role of the conserved histidine and aspartic acid residues in activity and
      stabilization of human gelatinase B: an example of matrix metalloproteinases.
AB  - Gelatinase B (MMP-9), a member of the matrix metalloproteinase family, is a zinc-
      and calcium-dependent endopeptidase that is known to play a role in tumor cell
      invasion and in destruction of cartilage in arthritis. It contains a conserved
      sequence. 400His-(X)3-His-(X)28-Asp-Asp-(X)2-436Gly, the function of which is
      under investigation. The conserved Asp-432 and Asp-433 residues were individually
      replaced with Gly; these substitutions reduced the gelatinolytic activity of the
      enzyme to 23% and 0%, respectively. Replacing Asp-433 with Glu, however,
      decreased the gelatinolytic activity of the enzyme by 93% and proteolytic
      activity of the enzyme for the Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 substrate by
      79%. The wild-type and D432G and D433E, mutant enzymes had similar Km values for
      the synthetic substrate and similar Ki values for the competitive inhibitor,
      GM6001. The kcat/Km values for D432G and D433E mutant enzymes, however, were
      reduced by a factor of approximately 4 and their KaCa values were increased by
      four- and sixfold, respectively. The significance of His-400 in the activity of
      the enzyme was assessed by replacing this residue with Ala and Phe. Both H400A
      and H400F mutants were inactive toward gelatin substrate. These data demonstrate
      that Asp-432, Asp-433, and His-400 residues are important for the activity of
      gelatinase B. His-400 may act as a zinc-binding ligand similar to the His-197 in
      interstitial collagenase (MMP-7) and Asp-432 and Asp-433 residues are probably
      involved in stabilization of the active site of the enzyme. The His-400 and Asp
      433 residues are conserved in all members of the MMP family. Therefore, our
      results are relevant to this group as a whole.

PMID- 8561851
TI  - Proton nuclear magnetic resonance studies on huwentoxin-I from the venom of the
      spider Selenocosmia huwena: 1. Sequence-specific 1H-NMR assignments.
AB  - The complete sequence-specific assignments of resonances in the 1H-NMR spectrum
      of huwentoxin-I from the Chinese bird spider, Selencocosmia huwena, is described.
      A combination of two-dimensional NMR experiments including 2D-COSY, 2D-NOESY, and
      2D-TOCSY has been employed on samples of the toxin dissolved in D2O and in H2O
      for assignment purposes. Protons belonging to spin systems for each of the 33
      amino acids were identified. The sequence-specific assignments were facilitated
      by the identification of d alpha N connectivities on the fingerprint regions of
      the COSY and NOESY spectra and were supported by the identification of dNN and d
      alpha N connectivities in the TOCSY and NOESY spectra. These studies provide a
      basis for the determination of the solution-phase conformation of this toxin.

PMID- 8561850
TI  - Intramolecular domain-domain interactions and intermolecular self-association in
      bovine prothrombin. A potentiometric and laser light-scattering study.
AB  - The interaction of bovine prothrombin with Ca2+ and Mg2+ ions was investigated by
      following H+ release as a function of metal ion concentration at pH 6 and pH 7.4
      at high and low ionic strength. Prothrombin Ca2+ and Mg2+ binding is
      characterized by high- and low-affinity sites. M2+ binding at these sites is
      associated with intramolecular conformational changes and also with
      intermolecular self-association. The pH dependence of H+ release by M2+ is bell
      shaped and consistent with controlling pKa values of 4.8 and 6.5. At pH 6 and low
      ionic strength, both Ca2+ and Mg2+ titrations following H+ release clearly show
      independent low- and high-affinity binding sites. Laser light scattering reveals
      that at pH 7.4 and low ionic strength, and at pH 6.0 and high ionic strength, the
      prothrombin molecular weight is between 73 and 98 kD. At pH 7.4 and high ionic
      strength, prothrombin is monomeric in the absence of metal ions, but appears to
      dimerize in the presence of M2+. At pH 6.0 and low ionic strength prothrombin
      exists as a dimer in the absence of metal ions and is tetrameric in the presence
      of Ca2+ and remains dimeric in the presence of Mg2+. These results and those for
      metal ion-dependent H+ release indicate that H+ release occurs concomitantly with
      association processes involving prothrombin.

PMID- 8561852
TI  - Analysis of the loop-helix interaction in bundle motif protein structures.
AB  - Molecular dynamics simulations and energy analysis have been carried out to study
      the structural mobility and stability of the four alpha-helix bundle motifs. The
      simulation results as well as the X-ray data show that the atomic RMS fluctuation
      is larger at the loop region for four representative proteins investigated:
      methemerythrin, cytochrome b-562, cytochrome c', and bovine somatotropin. The
      loop-loop, helix-helix, and loop-helix interactions are computed for the unfolded
      and folded proteins. In the folded and solvated protein structures the loop-helix
      interaction is stronger than the helix-helix interaction, especially in the
      electrostatic component. But the stabilization energies of both the loop-helix
      and the helix-helix interactions relative to those of an unfolded structure are
      of the same order of magnitude. The stabilization due to protein-solvent
      interaction is greater in the helix region than in the loop region. The
      percentage of hydrophilic solvent accessible area for the four proteins studied
      was calculated with the method of Eisenberg and McLachlan. The percentage of the
      hydrophilic area is greater in the loops than in the helices. A Poisson-Boltzmann
      calculation shows that the potential from the loops acting on a helix is
      generally more negative than that from other helices.

PMID- 8561854
TI  - An analysis of protein folding type prediction by seed-propagated sampling and
      jackknife test.
AB  - In the development of methodology for statistical prediction of protein folding
      types, how to test the predicted results is a crucial problem. In addition to the
      resubstitution test in which the folding type of each protein from a training set
      is predicted based on the rules derived from the same set, cross-validation tests
      are needed. Among them, the single-test-set method seems to be least reliable due
      to the arbitrariness in selecting the test set. Although the leaving-one-out (or
      jackknife) test is more objective and hence more reliable, it may cause a severe
      information loss by leaving a protein in turn out of the training set when its
      size is not large enough. In order to overcome the above drawback, a seed
      propagated sampling approach is proposed that can be used to generate any number
      of simulated proteins with a desired type based on a given training set database.
      There is no need to make any predetermined assumption about the statistical
      distribution function of the amino acid frequencies. Combined with the existing
      cross-validation methods, the new technique may provide a more objective
      estimation for various protein-folding-type prediction methods.

PMID- 8561853
TI  - A comparison of spectral and physicochemical properties of yeast iso-1 cytochrome
      c and Cys 102-modified derivatives of the protein.
AB  - Derivatives of yeast iso-1 cytochrome c, chemically modified at Cys-102 (Cys-102
      acetamide-derivatized monomer, Cys-102 thionitrobenzoate-derivatized monomer, Cys
      102 S-methylated monomer, and the disulfide dimer), exhibit different spectral
      and physicochemical properties relative to the native, unmodified protein,
      depending on the nature of the modifying group. The results of proton NMR studies
      on the Cys-102 acetamide-derivatized monomer of iso-1 ferricytochrome c indicate
      that the conformational characteristics of the heme environment in this protein
      derivative are intermediate between those of the unmodified monomer and disulfide
      dimer forms of the protein. Measurements of the pKa of the alkaline transitions
      of the five forms of iso-1 ferricytochrome c provided values of 8.89, 8.82, 8.67,
      8.47, and 8.50 for the unmodified monomer, S-methylated monomer, acetamide
      derivatized monomer, thionitrobenzoate-derivatized monomer, and disulfide dimer,
      respectively. The results of proton NMR studies of the reduced form of these
      proteins suggest that the heme environments of the unmodified monomer and
      disulfide dimer derivatives of iso-1 ferrocytochrome c are similar and indicate
      that treatment of the thionitrobenzoate-derivatized and disulfide dimer forms of
      the protein with sodium dithionite results in cleavage of the disulfide bonds at
      position 102. Circular dichroism studies reveal that only the disulfide dimer
      form of iso-1 ferricytochrome c exhibits a Soret CD spectrum which differs from
      the native, unmodified monomer in that the intensity of the negative band at
      approximately 420 nm is diminished in the spectrum of the dimer relative to the
      spectrum of the monomer. Soret CD spectra of the ascorbate-reduced form of all
      protein derivatives are similar. The process of "autoreduction" of yeast iso-1
      ferricytochrome c is shown to occur in the absence of a free sulfhydryl group at
      position 102 and is exacerbated under moderately high pH conditions. These
      results are suggestive of the presence of a redox-active amino acid, perhaps a
      tyrosine, in yeast iso-1 cytochrome c.

PMID- 8561855
TI  - Chaperone SecB: conformational changes demonstrated by circular dichroism.
AB  - The chaperone SecB, which is involved in protein export in Escherichia coli, is
      shown by circular dichroism measurements to contain a high content of beta
      pleated sheets. Prediction of the secondary structure of SecB is in good
      agreement with the observed content of beta-sheet. In accordance with the
      previous studies in which changes in conformation were assessed indirectly
      [Randall (1992), Science 257, 241-245], here we show that the conformation of
      SecB changes with the concentration of salt in the milieu and also when SecB
      interacts with a peptide ligand.

PMID- 8561856
TI  - Membrane-protein interaction and the molten globule state: interaction of alpha
      lactalbumin with membranes.
AB  - The insertion of soluble proteins into membranes has been a topic of considerable
      interest. We have studied the insertion of bovine alpha-lactalbumin into single
      bilayer vesicles prepared from egg phosphatidylcholine (PC). Fluorescence studies
      indicated rapid and tight binding of apo-alpha-lactalbumin (apo-alpha-LA) to PC
      vesicles as a function of pH. The binding was maximal at pH values which favor
      the formation of the molten globule state. As an increase of hydrophobic surface
      is observed in the molten globule state, this conformational state can provide a
      molecular basis for insertion of soluble proteins into membranes. The membrane
      bound complex formed at low pH (3.0) could be isolated and was found to be stable
      at neutral pH. The structural characterization of the apo-alpha-LA-PC complex was
      studied by fluorescence quenching using iodide, acrylamide, and 9,10
      dibromostearic acid. The results obtained indicated that some of the tryptophans
      of apo-alpha-LA were buried in the membrane interior and some were exposed on the
      outer side. Fluorescence quenching and CD studies indicated the membrane-bound
      conformation of apo-alpha-LA was some conformational state that is between the
      soluble, fully folded conformation and the molten globule state.

PMID- 8561857
TI  - Modulation of the redox state of the copper sites of human ceruloplasmin by
      chloride.
AB  - Incubation of human ceruloplasmin with physiological concentrations of chloride
      at neutral pH invariably caused dramatic changes of both the spectroscopic and
      the functional properties of the protein. The optical intensity at 610 nm
      increased up to 60%, with a concomitant decrease at 330 nm and the appearance of
      new bands between 410 and 500 nm. Signals previously undetectable appeared in the
      EPR spectrum. On the basis of computer simulations, they were interpreted as
      stemming from an oxidized type 1 copper site and from a half-reduced type 3
      copper pair. Removal of chloride completely restored the original optical and EPR
      lineshapes. Hydrogen peroxide, added to ceruloplasmin in the presence of
      chloride, was able to capture the electron of the half-reduced type 3 site and to
      yield a protein insensitive to subsequent removal and readdition of the anion. As
      a whole, the spectroscopic data indicate that a blue site is partially reduced in
      the resting protein and that, upon binding of chloride, human ceruloplasmin
      undergoes a structural change leading to displacement of an electron from the
      reduced type 1 site to the type 3 site pair. Chloride dramatically affected the
      catalytic efficiency of human ceruloplasmin. At neutral pH, the anion was an
      activator of the oxidase activity, being able to enhance up to tenfold the
      catalytic rate. At pH < 6, in line with all previous reports, chloride strongly
      inhibited the activity. At intermediate pH values, i.e., around 6, the effect was
      composite, with an activating effect at low concentration and an inhibitory
      effect at higher concentration. Since chloride is present at very high
      concentrations in the plasma, these results suggest that human ceruloplasmin is,
      in the plasma, under control of this anion.

PMID- 8561858
TI  - Specific cleavage of synthetic renin substrate by mouse gamma-nerve growth
      factor.
AB  - Results of the present investigation indicate that mouse gamma-nerve growth
      factor (gamma-NGF), which belongs to the kallikrein family of proteins,
      specifically cleaves the Phe-His bond of a synthetic renin substrate and exhibits
      rat-tonin-like activity. Since other mouse kallikreins do not cleave this bond,
      gamma-NGF may play a regulatory role in the generation of antiogensin-II.

PMID- 8561859
TI  - Evidence that apoB-100 of low-density lipoproteins is a novel Src-related protein
      kinase.
AB  - Protein-tyrosine kinases of signal transduction pathways occur and function
      intracellularly. In contrast, the low-density lipoprotein (LDL) particle
      circulates in plasma, where its function is to solubilize and transport lipid.
      Recently, several reports showed that LDL may have a role in signal transduction.
      We have identified a region in the apoB-100 primary structure which shows
      similarity to Src-homology-1 (SH1) domains, the kinase region of protein-tyrosine
      kinases. Results obtained in protein kinase assays of highly purified LDL showed
      that only the apoB-100 was phosphorylated, suggesting that apoB-100 has the
      capacity to undergo autophosphorylation like known protein-tyrosine kinases.
      Phosphorylation was not observed for any other apolipoprotein in LDL or for any
      component of high-density lipoprotein and lipoprotein [a]. Our results suggest
      that apoB-100 may be a novel and functional member of the src protein kinase
      family.

PMID- 8561860
TI  - Correlation of p53 immunoreactivity and sequencing in patients with glioma.
AB  - This study examines the relationship between p53 immunostaining and direct
      sequencing of polymerase chain reaction (PCR) products in 61 gliomas. Glioma
      tissues obtained from patients at surgery were analyzed immunohistochemically
      with the monoclonal antibody PAb1801 to detect p53 protein abnormalities.
      Amplified p53 cDNA from these samples was analyzed by direct sequencing. Four
      grades of p53 immunostaining were evaluated: grade 0 = no labeling, grade 1 =
      less than 5% labeled cells, grade 2 = 5-30% labeled cells, and grade 3 = more
      than 30% labeled cells. Twenty-six of 36 glioblastomas, 14 of 23 anaplastic
      gliomas, and none of two low-grade gliomas had positive p53 immunoreactivity.
      Direct sequencing of PCR-amplified p53 cDNA revealed that 10 glioblastomas, 11
      anaplastic gliomas, and no low-grade gliomas had mutations. Comparison of p53
      immunostaining and sequencing data revealed that among all the gliomas, mutations
      were found in three of 21 with p53 grade 0, one of 16 with p53 grade 1, seven of
      nine with p53 grade 2, and 10 of 15 with p53 grade 3. These results indicate a
      good correlation between the p53 immunostaining and sequencing data when the
      percentage of abnormal cells within the tumor was greater than 5% (p53 grades 2
      and 3). However, the correlation was poor when the percentage of abnormal cells
      was less than 5% (p53 grade 1) because of the limited sensitivity of sequencing
      techniques. Thus, p53 immunostaining may be more accurate in detecting p53
      alterations when the percentage of abnormal cells is small; however, in rare
      cases, p53 immunostaining may fail to detect mutations confirmed by sequencing.

PMID- 8561861
TI  - Effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine on intestinal polyp
      development in Apc delta 716 knockout mice.
AB  - Damage to the human adenomatous polyposis coli (APC) gene is responsible for not
      only familial adenomatous polyposis but also many sporadic cancers of the entire
      digestive tract. Using homologous recombination in embryonic stem cells, we
      recently constructed gene knockout mice with a truncation mutation in the Apc
      gene. These heterozygous mice developed intestinal polyps. We found that all
      microadenomas dissected from the earliest polyps had already lost the wild-type
      allele, indicating loss of heterozygosity (LOH) (Oshima et al., Proc. Natl. Acad.
      Sci. USA 92:4482-4486, 1995). Using these knockout mice, we investigated the
      effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP), one of the
      most abundant heterocyclic amines found in cooked meat and fish. When PhIP was
      fed to these mice at 400 ppm for 8 wk, the polyp distribution shifted to a larger
      size range, although the total polyp number did not change significantly.
      Similar, but weaker, effects were observed with the other heterocyclic amines 2
      amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline. On the other hand, intraperitoneal injections of 2-hydroxyamino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhlP) at a higher dose (50 mg/kg) for
      five consecutive days increased the polyp number significantly. This increment
      was not associated with mutations in the Apc gene; however, most polyps showed
      loss of the full-length Apc allele (LOH). These results suggest that PhIP affects
      intestinal polyp development by accelerating the growth rate of microadenomas. It
      is also possible that high doses of N-OH-PhIP increase the frequency of Apc gene
      LOH.

PMID- 8561862
TI  - Gap-junctional communication in normal and neoplastic prostate epithelial cells
      and its regulation by cAMP.
AB  - Gap-junctional communication and expression of gap junction-forming proteins were
      investigated in normal human prostate epithelial cells and in several malignant
      prostate cell lines. In comparison with normal cells, gap-junctional
      communication in malignant cells, as assayed by the transfer of 443-Da
      fluorescent tracer Lucifer yellow, was either reduced or not detected. Malignant
      cells expressed mRNA transcripts for connexin (Cx) 43, whereas normal cells
      expressed mRNA transcripts for Cx32 and Cx40. In both normal and malignant cells,
      gap-junctional communication was enhanced twofold to fivefold by treatment with
      forskolin, an agent known to increase intracellular levels of cAMP.
      Immunocytochemical staining with a Cx43-specific antibody revealed that in
      malignant cells this enhancement correlated with the number of gap junctions and
      occurred without any qualitative or quantitative alteration in Cx43 mRNA or
      protein. Moreover, western blot analyses showed that both control and forskolin
      treated malignant cells expressed only one form of Cx43. Our data suggest that
      gap-junctional communication in both normal and malignant prostate cells may be
      regulated by hormones that work via a cAMP-dependent signal transduction pathway.
      Thus, both normal and malignant cells offer a new experimental model system in
      which interactions between a hormonal form of cellular communication and
      intercellular communication mediated via gap junctions can be studied.

PMID- 8561863
TI  - A novel clonality assay for the mouse: application to hepatocellular carcinomas
      induced with diethylnitrosamine.
AB  - A polymerase chain reaction-based clonality assay was developed for mouse tumors
      and cellular proliferations of the mouse. This assay was based on a polymorphism
      of the phosphoglucokinase-1 (Pgk-1) gene on the X chromosome between two
      different mouse subspecies and the different methylation patterns of active and
      inactive X chromosomes. All 15 tumor cell lines examined showed one of the two
      allelic bands on gel electrophoresis, which is consistent with the theory that
      tumor cell lines are monoclonally derived. This suggests that the Pgk-1 system is
      useful for clonality studies that will give insight into cancer development. With
      this method, nine hepatocellular carcinomas were examined, and eight showed
      monoallelic patterns. The remaining tumor exhibited a biallelic pattern, which is
      suggestive of polyclonal origin; however, other possibilities are discussed.

PMID- 8561864
TI  - DNA polymerase beta gene mutations in human bladder cancer.
AB  - We examined 24 human bladder cancer tissues for possible mutations in the entire
      coding region of the human DNA polymerase beta gene using polymerase chain
      reaction analysis, single-strand conformational polymorphism analysis of RNA, and
      sequence analysis. DNA polymerase beta gene mutations were observed in four of
      the 24 cases (16.7%) and included three missense point mutations and a single
      base insertion. The single base insertion was also observed in our previous study
      of human prostate cancer, suggesting that this region may be a hot spot for
      mutation of the DNA polymerase beta gene. No clinical or pathological association
      was found among the four cases that contained the mutation. Three of the four
      cases with DNA polymerase beta gene mutation had mutations of the p16 or RB genes
      or loss of heterozygosity of the p53 and APC gene loci. The results of the study
      presented here suggest that DNA polymerase beta gene mutations, in combination
      with mutations of tumor suppressor genes, may be involved in certain cases of
      human bladder cancer.

PMID- 8561866
TI  - Infrequent CDKN2 mutation in human differentiated thyroid cancers.
AB  - We examined the frequency of cyclin-dependent kinase (CDK) N2 alterations in
      differentiated and anaplastic thyroid cancers to assess the involvement of CDKN2
      in the development of these cancers. The CDKN2 gene, which encodes the cell-cycle
      regulator p16, was recently shown to be mutated or deleted in many tumor cell
      lines. Its role in the genesis of primary tumors is uncertain, however. Tumor and
      corresponding normal DNAs were prepared by microdissection of paraffin-embedded
      tissue blocks or from frozen surgical specimens of 15 papillary, 15 follicular,
      and five anaplastic thyroid carcinomas. The entire CDKN2 coding region was
      screened by single-strand conformational variant analysis and direct sequencing
      of variants. The presence of homozygous deletions was evaluated by multiplex
      polymerase chain reaction (PCR) analysis. Loss of heterozygosity (LOH) in the
      CDKN2 region was assessed by using flanking polymorphic markers. Two somatic
      missense mutations were found among the 35 thyroid cancers, one in a follicular
      tumor and one in an anaplastic tumor. Multiplex PCR suggested the presence of
      homozygous deletion in one anaplastic tumor and hemizygous deletions in four
      tumors. LOH studies revealed loss of 9p sequences in four follicular (27%) and
      two anaplastic (50%) cancers. Our data suggest that alterations in CDKN2 played a
      role in a minority of thyroid cancers (three of 35). LOH in the region of CDKN2
      is seen in a significant proportion of follicular and anaplastic but not
      papillary cancers. Loss of 9p sequences suggests a role for a tumor suppressor
      gene in the development of follicular and anaplastic thyroid cancers.

PMID- 8561865
TI  - Detection of amphiregulin and Cripto-1 in mammary tumors from transgenic mice.
AB  - Epidermal growth factor family members are widely expressed in human breast
      cancer and are thought to play an important dual role in mammary gland
      development and tumorigenesis. Overexpression of two relatively new members of
      this family, amphiregulin (AR) and Cripto-1 (CR-1), has been previously shown to
      transform immortalized human and mouse mammary epithelial cells. Here, we extend
      these results and address the disregulated expression of AR and CR-1 in many
      types of transgenic neoplastic mouse mammary tissues. Transgenic mouse strains
      overexpressing the oncogenes transforming growth factor-alpha, neu, int-3,
      polyoma virus middle T antigen, and simian virus 40 large T antigen have been
      previously shown to develop spontaneous mammary neoplasia. These models were each
      examined for mammary-tumor expression of AR and CR-1 by reverse transcription
      polymerase chain reaction, western blot, and immunocytochemical analyses. Mammary
      tumors from each source expressed AR and CR-1. Western blot analysis revealed
      that, in all mammary tumors, AR and CR-1 protein species were processed
      differently than in virgin and lactating mouse mammary tissue. In addition,
      immunohistochemical detection of AR and CR-1 in tumor tissue revealed different
      patterns of growth-factor localization in different types of transgenic mouse
      mammary-derived tumors. These findings are consistent with the possibility of
      widespread roles for AR and CR-1 in the promotion and/or progression stages of
      mouse mammary tumorigenesis.

PMID- 8561867
TI  - Matrilysin expression in human prostate carcinoma.
AB  - The metalloproteinases, a multigene family of metal-requiring enzymes, have been
      suggested to play a role in tumor invasion and metastasis. Previously, we
      demonstrated that human primary prostate tumors express higher levels of
      matrilysin and gelatinase A mRNA than normal prostate does. In the study
      presented here, we used in situ hybridization and immunohistochemical staining of
      serial sections of paraffin-embedded primary prostate tumors to compare the sites
      of matrilysin and gelatinase A expression and protein localization. These results
      confirmed the epithelial nature of matrilysin expression and protein
      localization. In contrast, gelatinase A mRNA was localized to the interstitial
      stroma, whereas the protein was associated with the epithelial tumor cells. In
      situ hybridization was also used to demonstrate that gelatinase B expression was
      restricted to macrophages infiltrating the tumors. Proteins isolated from an
      additional set of frozen tumor specimens were analyzed by western blotting to
      determine the relative amounts of matrilysin in the active and proenzyme forms.
      The western analyses demonstrated that in all cases in which matrilysin was
      detected, at least some of the enzyme was in the active form. These results are
      discussed with respect to the possible role these enzymes may play in prostate
      tumor progression.

PMID- 8561868
TI  - ras effector loop mutations that dissociate p120GAP and neurofibromin
      interactions.
AB  - ras proteins are positively regulated by nucleotide exchange factors and
      negatively regulated by GTPase-activating proteins (GAPs). Two GAPs have been
      found in mammalian cells, p120GAP and neurofibromin, the product of the type 1
      neurofibromatosis (NF1) gene. A library of substitutions in the effector loop
      region of ras in an Escherichia coli plasmid expression system was screened for c
      Ha-ras species with altered GAP interactions. Several substitutions
      preferentially disrupted the interaction of ras with p120GAP as compared with the
      interaction with the recombinant GAP-related domain of neurofibromin (NF1-GRD).
      The most extreme example, Tyr32His, encoded a ras species that was unaffected by
      p120GAP but was stimulated normally by NF1-GRD. Tyr32His was weakly transforming
      in Rat2 cells. Tyr32His ras was primarily GDP-bound in quiescent Rat2 cells,
      although it rapidly associated with GTP after treatment of cells with epidermal
      growth factor. These results show that the NF1 product has less stringent
      requirements than p120GAP for ras effector domain structure and that negative
      regulation of ras can be achieved in rat fibroblasts by the product of NF1.

PMID- 8561869
TI  - Differential spontaneous transformation in vitro of newly established mouse
      fibroblast lines carrying or lacking the viable yellow mutation (Avy) of the
      mouse agouti locus.
AB  - The pleiotropic effects of the viable yellow mutation (Avy), an allele of the
      mouse agouti coat-color locus, include increased susceptibility to spontaneous
      and chemically induced tumors that affect a wide variety of tissues. As a first
      step toward understanding the molecular basis of this phenomenon, we established
      permanent fibroblast-like cell lines from newborn Avy/a and control congenic a/a
      mice and compared their growth characteristics in vitro. From the VY/WffC3Hf/Nctr
      and YS/WffCH3f/Nctr-Avy inbre strains, each of which carries the Avy allele on a
      congenic background, 38 clonal Avy/a and 16 clonal a/a lines were established.
      Regardless of inbred strain, all Avy/a cell lines exhibited a significant degree
      of spontaneous transformation, as assessed by focus formation in monolayer
      culture, whereas none of the a/a cell lines formed foci in prolonged cultures. To
      test whether changes in dosage of the Avy- or a-bearing chromosomes were related
      to these events, we analyzed each cell line with a closely linked molecular probe
      from the Emv-15 locus, which in the VY strain detects a restriction fragment
      length variant (RFLV) informative for the Avy- and a-bearing chromosomes. Most of
      the transformed foci maintained heterozygosity for RFLVs detected by the probe,
      but two of the transformants lost the a-associated RFLV, and at least one of the
      transformants exhibited amplification of the Avy-associated RFLV. When the
      transformants were analyzed with 5' sequences derived from the recently cloned
      agouti gene, three of eight transformants lost the a-associated RFLV, and two of
      the transformants showed amplification of the Avy-associated RFLV. Reverse
      transcriptase-polymerase chain reaction assays indicated that agouti RNA was
      detected in Avy/a, not a/a cell lines. Surprisingly, some of the Avy/a
      transformants lacked agouti RNA. These results suggest that deregulated
      expression of the Avy allele is required for the initiation but not for the
      maintenance of transformation of the Avy/a cell cultures. These cell lines may
      provide an in vitro culture system for studying the effect of the agouti gene on
      tumorigenicity as well as to potentially study other pleiotropic phenotypes.

PMID- 8561870
TI  - Low-dose aspirin therapy and placental pathology in women with poor prior
      pregnancy outcomes.
AB  - PROBLEM: To determine if low dose aspirin therapy improves placental histology in
      women with a prior complicated pregnancy demonstrating uterine vascular
      pathology. METHOD: A retrospective chart review identified patients with a prior
      complicated pregnancy with placental changes showing uterine vascular pathology
      (control pregnancy, CP). In the treated pregnancy (TP), 81 mg/day of ASA was
      started prior to 10 weeks. Placental reports from the CP and TP were reviewed.
      Pregnancy outcomes and placental histology from the CP were compared to the TP
      for each patient. RESULTS: Thirteen patients were enrolled. The majority of
      patients (8/13, 61.5%) exhibited recurrent, histologic evidence of uterine
      vascular pathology in the TP. The TP was more likely to be uncomplicated (P <
      0.05), delivered after 36 weeks (P < 0.05), and result in the delivery of a
      viable infant (P < 0.05) compared to the CP. CONCLUSIONS: Despite an improvement
      in outcomes in the aspirin treated pregnancy, histologic evidence of uterine
      vascular pathology persisted in the majority of women with a prior complicated
      pregnancy demonstrating similar placental lesions. Abnormal placental histology
      may be useful in identifying a group of women with poor obstetrical histories who
      could benefit from low-dose aspirin therapy.

PMID- 8561871
TI  - Generation and characterization of monoclonal antibodies specific to surface
      antigens of human trophoblast cells.
AB  - PROBLEM: To generate and utilize specific monoclonal antibodies for routine fetal
      cell isolation from the maternal circulation. METHODS: Monoclonal antibodies
      specific to human trophoblast cell surface antigens were generated and
      characterized. After cell fusion, antibodies secreted by hybridomas were screened
      by enzyme-linked immunosorbent assay and immunohistochemical assays. RESULTS: By
      using cultured BeWo choriocarcinoma cells or the membrane fraction of human
      placenta as the immunogen, seven (BW-108, 110, 123, 124, HP-15, 16 and 17)
      antibodies specific to the surface antigens of trophoblast were produced. They
      were shown to have little cross-reactivity to other human tissues. Among the
      antibodies raised against human sperm, HSA-10 was also found to cross-react with
      human trophoblast, but not detected in other tissues. When immobilized to
      magnetic beads, these antibodies were shown to react only with BeWo cells in
      suspension, but not blood cells and ovarian carcinoma cell line, OC-3-VGH.
      CONCLUSION: Therefore, these antibodies may have potential application in fetal
      trophoblast cell isolation from the maternal circulation for prenatal genetic
      diagnosis.

PMID- 8561872
TI  - Amniochorion: a source of interleukin-8.
AB  - PROBLEM: Preterm labor and premature rupture of the membranes are major
      complications of pregnancy. We have reported the possible role of amniochorionic
      membrane in the production of inflammatory cytokines and the early onset of
      labor. This study was conducted to detect the expression of IL-8 mRNA and peptide
      production in cultured fetal membranes. METHOD: Amniochorionic membranes were
      collected from women undergoing elective cesarean section at term. Membranes were
      cultured in an organ explant system and the expression of IL-8 was studied over a
      10-day period by RT-PCR and in situ hybridization. IL-8 peptide localization was
      accomplished using immunocytochemistry. RESULTS: Constitutive expression of IL-8
      mRNA in cultured fetal membranes was demonstrated in both amniotic and chorionic
      leave cells. mRNA and peptide for IL-8 was homogeneously distributed throughout
      the amniotic and chorionic cells. CONCLUSION: Human amniochorionic membrane is a
      source of IL-8 mRNA and peptide.

PMID- 8561873
TI  - Soluble tumor necrosis factor receptor in serum and urine throughout normal
      pregnancy and at delivery.
AB  - PROBLEM: To determine the concentration of the two soluble tumor necrosis factor
      receptors (sTNFR), sp55 and sp75, in healthy pregnant women. METHOD: Serum and
      urine samples were longitudinally collected from a group of pregnant women (N =
      53) five times throughout pregnancy. Maternal and umbilical sera were obtained
      from some of the deliveries (N = 31). The samples were analysed using ELISA based
      on two monoclonal antibodies (IV4E and 3H5) against the soluble tumor necrosis
      factor receptors (sp55 and sp75). RESULTS: Serum concentration of sp55 and sp75
      were increased in pregnant women compared to that of nonpregnant controls.
      Concentration of both sTNFRs increased towards term. Labor was associated with
      further increase of sp55. Concentrations of sp55 and sp75 in umbilical serum were
      significantly higher than those of maternal serum. Significant correlations were
      observed between maternal and umbilical sTNFR concentrations. CONCLUSIONS: The
      current study suggests that pregnancy is associated with an activation of
      mechanisms regulating the biological activities of TNF.

PMID- 8561874
TI  - Circulating tumor necrosis factor (TNF)-alpha in normally cycling women and
      patients with premature ovarian failure and polycystic ovaries.
AB  - PROBLEM: The purpose of this study was to investigate the levels of tumor
      necrosis factor (TNF)-alpha in sera of infertile patients having premature
      ovarian failure (POF) and polycystic ovaries (PCO), and to compare the levels
      with those in age-matched normally cycling women. METHOD: Levels of TNF-alpha,
      luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2)
      were measured in the sera of infertile and normal women by the enzyme linked
      immunosorbent assay (ELISA), fluorescent immunoassay and radioimmunoassay (RIA),
      respectively. Multiple groups comparisons were performed using Dunnet's test.
      Post-hoc analysis was performed using a Tukey-Kramer test. P < 0.05 was
      considered statistically significant. RESULTS: TNF-alpha levels were
      significantly (P = 0.003 to < .0001) lower in the sera of patients with POF
      compared to sera of controls and patients with PCO. CONCLUSIONS: TNF-alpha may
      have a role in ovarian function. Derangement in follicular development, luteal
      function and atresia results in a change of circulating TNF-alpha levels.

PMID- 8561875
TI  - Gamma delta T-cell subset distribution in human semen from fertile donors.
AB  - PROBLEM: Gamma delta T-cell subset distribution has not been fully investigated
      in normal human semen. METHODS: We therefore carried out experiments by using a
      direct immunofluorescence staining technique followed by two-color
      cytofluorimetric analysis on mononuclear cell (MC) suspensions from ejaculates of
      ten healthy, fertile volunteers. Autologous peripheral blood MC were
      simultaneously analyzed and the results used for statistical comparison. RESULTS:
      The proportion of normal human semen lymphocytes bearing the gamma delta T-cell
      receptor for antigen was greatly increased compared with autologous circulating
      counterparts. Interestingly, the rise was mainly due to an overexpansion of cells
      expressing V delta 1 gene-encoded determinants on their surface. This contrasts
      with the normal blood picture, where most gamma delta T cells express V delta 2
      conformational epitopes. CONCLUSIONS: The numerical and phenotypical differences
      in semen gamma delta T lymphocytes provide further evidence of a defined
      migrating lymphocyte subset balance in anatomically and physiologically distinct
      areas of the body. Their functional role, in terms of both helper and suppressor
      cytotoxic activities in the nonsterile proximal portions of the male genital
      tract, now needs to be explored in detail.

PMID- 8561876
TI  - Human peritoneal macrophage and T lymphocyte populations in mild and severe
      endometriosis.
AB  - PROBLEM: The aim of this study was to characterize the phenotype of peritoneal
      lymphocyte and macrophage populations in mild versus severe endometriosis.
      METHOD: Using dual staining, antigen expression on peritoneal leukocytes from 24
      women with endometriosis and 21 control patients was analyzed by flow cytometry.
      RESULTS: All groups had CD4:CD8 ratios of 0.6, with subpopulations of CD8+ cells
      expressing cytotoxic marker S6F1. Mild and severe endometriosis patients had
      increased CD3/DR+ cells, relative to controls. Two populations of macrophages
      were identified by size in all groups. Mild endometriosis patients had increased
      percentages of small macrophages expressing CD14 and HLA DQ, compared to controls
      and severe disease patients. In severe disease patients, antigen expression on
      small macrophages did not differ from controls, but decreased percentages of
      large macrophages expressed CD14 relative to controls and mild disease patients.
      CONCLUSION: All women with endometriosis exhibit activated peritoneal
      lymphocytes, whereas macrophage expression of CD14 is differentially expressed as
      a function of disease stage. Alterations in the functional capacity of these
      cells may contribute to the pathophysiology of this disease.

PMID- 8561877
TI  - Constitutive secretion of interleukin-6 by human decidual stromal cells in
      culture. Regulatory effect of progesterone.
AB  - PROBLEM: Although several studies have demonstrated that decidual stromal cells
      (DSC) can secrete cytokines in culture, none of these studies documented the
      purity of the cultures. Since other cells of the decidua, such as macrophages and
      epithelial cells, also produce cytokines, it is important to ensure purity of the
      culture so that cytokine production can be ascribed with confidence to DSC.
      METHOD: DSC from early human pregnancies were highly purified and maintained in
      culture. Basal secretion by these cells of IL-6, together with other cytokines
      considered critical for pregnancy (IL-1 beta, TNF alpha and IFN gamma), was
      measured with immunological techniques. RESULTS: We found that DSC in culture
      produce insignificant quantities of IL-1 beta, TNF alpha and IFN gamma, but
      appreciable amounts of IL-6. The production of this later cytokine was, however,
      inhibited by the effect of progesterone. CONCLUSIONS: Basal production of IL-6 by
      DSC may be involved in physiological functions at the maternal-fetal interface.
      Nevertheless, the secretion of this cytokine is regulated by progesterone,
      probably to prevent excessive production of this cytokine from triggering an
      inflammatory response that might compromise pregnancy.

PMID- 8561878
TI  - The ovarian dysgenesis normally induced by neonatal thymectomy is prevented by
      the prior administration of estrogen.
AB  - PROBLEM: Neonatal thymectomy (Tx) and estrogen (E2) administration disrupt the
      reproductive and immune systems of female mice. The current experiment examined
      the combined effects of the two procedures on ovarian function, performed in
      sequence, and in reverse sequence. METHOD: Groups of (C57BL/6J x A/J)F1 (B6A)
      female mice were given four daily injections of 20 micrograms estradiol-17 beta,
      either from 0 days to 3 days, or from 3 days to 6 days postpartum. In some groups
      this regimen was combined with thymectomy performed either prior to steroid
      injection (TX-3), or after steroid treatment (TX-4). Animals were sacrificed
      between 100 and 110 days of age then ovaries evaluated via light microscopy for
      dysgenesis and follicular cysts. RESULTS: When E2 treatment followed Tx, the
      incidence of ovarian dysgenesis was unchanged (study 1, Tx + E2 = 60% ovarian
      dysgenesis; Tx = 63% ovarian dysgenesis) (study 2, Tx + E2 = 46% ovarian
      dysgenesis; Tx = 45% ovarian dysgenesis). In contrast, when E2 was given before
      Tx, ovarian dysgenesis did not occur (study 2, E2 + Tx = 0% ovarian dysgenesis;
      Tx = 46% ovarian dysgenesis). Ovaries from E2 + Tx animals were characteristic of
      ovaries from E2-injected animals without Tx. CONCLUSION: The results indicate
      that E2 injection prevents Tx-induced ovarian dysgenesis, suggesting E2
      activation of an extrathymic pathway for thymus function.

PMID- 8561879
TI  - Active immunization against LHRH alone or combined with LHRH-analogue treatment
      impedes growth of androgen-dependent prostatic carcinoma.
AB  - PROBLEM: To determine whether active immunization against LHRH can serve as
      treatment for androgen-dependent prostatic carcinoma. METHOD: Male rats of
      Copenhagen X Fisher strain, implanted with Dunning R-3327 prostatic carcinoma
      cells were either immunized against LHRH, treated with LHRH-antagonist, or
      received a combined treatment of active immunization against LHRH and LHRH
      antagonist. RESULTS: Testicular histology was consistent with infertility in all
      treatment groups. The rate of tumor growth was inhibited by all three treatment
      regimens. Tumor size increased by 3.8 +/- 1.4 cm2 in the LHRH-antagonist group,
      3.2 +/- 1.1 cm2 in the immunized group, and 1.0 +/- 0.4 cm2 in the combined
      treatment group, as compared to 8.2 +/- 2.6 cm2 in non-treated control group.
      CONCLUSION: LHRH-antagonist administration combined with immunization against
      LHRH appeared to exert a synergistic effect. This may be due to the blockade of
      prostatic LHRH-like receptors by the antagonist, while androgen depletion was
      rapidly achieved by LHRH-antagonist, and maintained by continued gonadotropin
      suppression caused by active immunization against LHRH once antagonist treatment
      had been discontinued.

PMID- 8561880
TI  - [Determination of oleanolic acid in the root of Achyranthes bidentata Bl. from
      different places of production by TLC-scanning].
AB  - The contents of oleanolic acid in the root of Achyranthes bidentata and A. aspera
      from different places of production have been determined by dual-wavelength TLC
      scanning. The results show that the content of oleanolic acid is 0.91%-1.14% in
      cultured A. bidentata, 0.78%-1.42% in A. bidentata natural and 0.054% in A.
      aspera. The average recovery is 98.63%.

PMID- 8561881
TI  - [Tissue culture of bulbus Fritillariae cirrhosae].
AB  - On the MS culture medium containing some phytohormones, regenerated Bulbus
      Fritillariae Cirrhosae can induce without low temperature callus which
      differentiates into a plant. The total alkaloid content of the culture is two
      four times that of the stock and commercial Bulbus Fritillariae Cirrhosae. The
      free-protein atlas of the culture is consistent with that of the stock.

PMID- 8561882
TI  - [Processing of pyritum from different sources].
AB  - Studies on the processing of Pyritum from different source were conducted by
      means of indentical technological procedure using total sulphur, S,FeS2 and Fe7S8
      as indexes. The results showed considerable differences in compositions of the
      processed products.

PMID- 8561883
TI  - [Determination of total saccharide and several main saccharides in Rehmannia
      glutinosa Libosh, and its processed products].

PMID- 8561884
TI  - [Determination of puerarin in radix Puerariae and yufengningxin tablets by HPLC].
AB  - The contents of puerarin in Radix Puerariae and Yufengningxin Tablets were
      determined by HPLC. The average rates of recovery were 97.19% and 100.68%
      respectively, and RSD 1.05% and 1.31% respectively.

PMID- 8561885
TI  - [A new method for qualitative determination of astragaloside].
AB  - A multi-function column has been devised for qualitative determination of
      astragaloside in Yuanheng-yitai Chutang Tablets. The result of experiment shows
      that the method is convenient fast and stable.

PMID- 8561886
TI  - [Chemical constituents of roots of Ampelopsis brevipedunculata (Maxim) Trautv].
AB  - Eight compounds have been isolated from the roots of Ampelopsis-brevi pedunculata
      and identified as beta-amyrin, betulin, vanillic acid, ethyl gallate, kaempferol,
      3,5-dimethoxy-4-hydroxybenzoic acid, aromadendrol and resveratrol. They are
      isolated from this plant for the first time.

PMID- 8561887
TI  - [Chemical constituents of the Sparganium stoloniferum Buch.-Ham].
AB  - Three compounds were obtained for the first time from the rhizome of Sparganium
      stoloniferum and identified as beta-sitosterol, succinic acid and daucosterol by
      comparing with the known specimens. Twenty-one fatty acids were separated and
      identified by GC-MS.

PMID- 8561888
TI  - [Effects of three kinds of decoction on histopathology of gastric mucosa, gastric
      pH and the content of bile acid in experimental chronic gastritis in rats].
AB  - Experimental chronic gastritis (ECG) models were established in rats by inserting
      a spring into pyloric canal as well as feeding sodium deoxycholate. An experiment
      was undertaken to observe the therapeutic effects of three formulas of
      traditional Chinese medicine "Shipitong", "Ganpingyangwei" and "Weile". The
      experimental results show that all of the three decoctions can reduce gastric pH
      and bile acid of the ECG rats and make gastric mucosal histomorphology of these
      rats change markedly.

PMID- 8561890
TI  - [A review of the adverse effects of Chinese herbal drugs as published in Chinese
      journals in 1993 and 1994].

PMID- 8561889
TI  - [Effects of Chinese ginseng root and stem-leaf saponins on learning, memory and
      biogenic monoamines of brain in rats].
AB  - The present investigation has shown that Ginseng root saponins (ig, 50mg/kg x 7d)
      facilitate the learning and memory of normal male Wistar rats, while the effect
      of Ginseng stem-leaf saponins (ig, 50mg/kg x 7d) on antielectrconvulsive shock
      induced impairment of memory consolidation in rats is more intensive than that of
      root saponins. Both Ginseng root and stem-leaf saponins can significantly raise
      the levels of biogenic monoamines in normal rat's brain.

PMID- 8561891
TI  - Hantaviruses: clinical, microbiologic, and epidemiologic aspects.
AB  - Hantaviruses comprise a genus of the family Bunyaviridae. Bunyaviruses are
      enveloped viruses with a negative-sense, tripartite RNA genome. Hantaviruses are
      etiologic agents for two acute and severe illnesses of man, hemorrhagic fever
      with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Each
      hantavirus is primarily associated with a single rodent host species or genus,
      and is transmitted to man through accidental inhalation or ingestion of virus
      contaminated rodent excreta. The distribution of hantaviruses is worldwide. HFRS
      is caused by infection with Hantaan, Seoul, Dobrava/Belgrade, and Puumala
      hantaviruses, all of which are enzootic in murid rodents of Old World origin. HPS
      is caused by any of several hantavirus species associated with indigenous New
      World rodents of the subfamily Sigmodontinae, family Muridae. HFRS and HPS have
      numerous common epidemiologic, clinical, and laboratory characteristics. Common
      features include fever, myalgia, thrombocytopenia, neutrophilia, and a profound
      capillary leak syndrome associated with hypotension, decreased cardiac output,
      and shock. Worldwide, HPS is much less common than HFRS but is associated with a
      higher mortality rate. Recovery from hantavirus disease is generally complete,
      although chronic renal insufficiency may be a rare sequel of HFRS.

PMID- 8561892
TI  - The genetics and pathophysiology of type II and gestational diabetes.
AB  - The development of both type II diabetes and gestational diabetes is probably
      governed by a complex and variable interaction of genes and environment.
      Molecular genetics has so far failed to identify discrete gene mutations
      accounting for metabolic changes in NIDDM. Both beta cell dysfunction and insulin
      resistance are operative in the manifestation of these disorders. Specific and
      sensitive immunoradiometric assays found fasting hyperproinsulinemia and first
      phase hypoinsulinemia early in the natural history of the disorder. A lack of
      specificity of early radioimmunoassays for insulin resulted in measuring not only
      insulin but also proinsulins, leading to overestimation of insulin and misleading
      conclusions about its role in diabetes. The major causes of insulin resistance
      are the genetic deficiency of glycogen synthase activation, compounded by
      additional defects due to metabolic disorders, receptor downregulation, and
      glucose transporter abnormalities, all contributing to the impairment in muscle
      glucose uptake. The liver is also resistant to insulin in NIDDM, reflected in
      persistent hepatic glucose production despite hyperglycemia. Insulin resistance
      is present in many nondiabetics, but in itself is insufficient to cause type II
      diabetes. Gestational diabetes is closely related to NIDDM, and the combination
      of insulin resistance and impaired insulin secretion is of importance in its
      pathogenesis.

PMID- 8561893
TI  - Examination of mammalian basic helix-loop-helix transcription factors using a
      yeast one-hybrid system.
AB  - Basic helix-loop-helix (bHLH) transcription factors play diverse roles in
      controlling many developmental events. Although a great deal is understood about
      how bHLH factors activate gene transcription via E-box DNA consensus sequences,
      studies of bHLH factor function in higher eukaryotes often have been hindered by
      the presence of multiple family members. As a first step in developing a
      simplified in vivo system to examine bHLH factor activities, we examined whether
      the bHLH muscle regulatory factors MRF4 and MyoD function appropriately in yeast.
      We show that Gal4-MRF4 fusion proteins, or native MRF4 proteins, activate
      expression of an E-box HIS3 reporter gene whereas MyoD proteins remain inactive.
      Deletion of the MRF4 transcription activation domain (TAD) or point mutations
      that abolish MRF4 DNA interactions inhibit HIS3 expression. Substitution of the
      MRF4 TAD with the Gal4 TAD also produces a functional protein, demonstrating that
      these transcription activation domains are functionally equivalent in yeast.
      Replacement of the MRF4 TAD with the related MyoD TAD, however, generates an
      inactive protein, suggesting that some specificity exists between bHLH family
      members. Using this experimental system, we also demonstrate that mammalian cDNA
      libraries can be screened successfully for cDNAs encoding novel bHLH proteins
      that interact with E-box targets. Thus, this in vivo yeast system provides a
      novel approach to facilitate functional studies of bHLH factor regulation.

PMID- 8561894
TI  - Thiopurine methyltransferase pharmacogenetics: human gene cloning and
      characterization of a common polymorphism.
AB  - Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine
      drugs. Individual variation in the toxicity and therapeutic efficacy of these
      drugs is associated with a common genetic polymorphism that controls levels of
      TPMT activity and immunoreactive protein in human tissues. Because of the
      clinical significance of the "pharmacogenetic" regulation of this enzyme, it
      would be important to clone the gene for TPMT in humans and to study the
      molecular basis for the genetic polymorphism. As a first step toward cloning the
      gene for TPMT, we used the rapid amplification of genomic DNA ends to obtain a
      TPMT-specific intron sequence. That DNA sequence was used to design primers for
      the polymerase chain reaction (PCR), which made it possible to determine that the
      active gene for TPMT is located on human chromosome 6. A TPMT-positive cosmid
      clone was then isolated from a human chromosome 6-specific genomic DNA library,
      and the gene was sublocalized to chromosome band 6p22.3 by fluorescence in situ
      hybridization. The gene for TPMT was found to be approximately 34 kb in length
      and consisted of 10 exons and 9 introns. On the basis of the results of 5'-rapid
      amplification of cDNA ends, transcription initiation occurred at or near a point
      89 nucleotides upstream from the translation initiation codon of previously
      reported TPMT cDNAs. Once the structure of the TPMT gene had been determined, it
      was possible to perform the PCR with primers complementary to the sequences of
      introns flanking each exon that encodes enzyme protein with template DNA obtained
      from subjects with known phenotypes for the TPMT genetic polymorphism. This DNA
      was isolated from blood samples from 4 unrelated subjects with genetically low
      TPMT activity and 4 unrelated subjects with high TPMT activity. All subjects with
      low TPMT activity were homozygous for two point mutations--a G-->A transition at
      nucleotide 460 in exon 7 and an A-->G transition at nucleotide 719 in exon 10.
      Both mutations resulted in alterations in amino acid sequence, with Ala-154-->Thr
      and Tyr-240-->Cys, respectively. All DNA samples isolated from the blood of
      subjects with high TPMT activity contained "wild-type" sequence. Results obtained
      with these blood samples were confirmed when DNA from four human liver samples
      with high TPMT activity were found to have wild-type sequence at nucleotides 460
      and 719, while three liver samples with intermediate enzyme activity (i.e.,
      samples presumed to be heterozygous for the polymorphism) were heterozygous for
      the exon 7 and exon 10 mutations present in the blood samples of homozygous low
      subjects. Transient expression in COS-1 cells of TPMT expression constructs that
      contained both of the mutations in exons 7 and 10, as well as each independently,
      demonstrated that each mutation, as well as both together, resulted in decreased
      expression of TPMT enzymatic activity and immunoreactive protein. Molecular
      cloning and structural characterization of the TPMT gene as well as elucidation
      of the molecular basis for a common TPMT genetic polymorphism will help make it
      possible to develop DNA-based diagnostic tests for the polymorphism and to
      determine the mechanism by which it results in decreased expression of this
      important drug-metabolizing enzyme.

PMID- 8561895
TI  - Association of signaling proteins with a nonmitogenic heterodimeric complex
      composed of epidermal growth factor receptor and kinase-inactive p185c-neu.
AB  - The functional consequences of heterodimer formation between the epidermal growth
      factor receptor (EGFr) and the p185c-neu receptor tyrosine kinase include
      increased mitogenic and transformation potencies. To determine the possible
      alteration of signal transduction pathways resulting from this heteromeric
      complex, the capacity of several signaling proteins to associate with the
      heterodimeric receptors has been assayed. The in vivo interaction with the
      EGFr/p185c-neu heterodimer of several signal transduction proteins, including
      phospholipase C-gamma 1 (PLC-gamma 1), the p85 subunit of phosphotidylinositol 3
      kinase, the ras GTPase activating protein, SHC, NCK, p72RAF, and the tyrosine
      phosphatase SHPTP2, was measured by coimmunoprecipitation. The binding of these
      signaling proteins to a complex composed of EGFr and a kinase-inactive form of
      p185 (p185K757M) was not impaired, even though the mitogenic and transformation
      activity of this complex had been abrogated. In addition, the EGF-induced
      phosphorylation of GAP, p85, and PLC-gamma 1 did not correlate with the dominant
      negative action of p185K757M on EGFr function. Thus, substrate association and
      phosphorylation do not correlate stringently with the mitogenic and transforming
      activity of this receptor complex, suggesting additional pathways or mechanisms
      vital to EGFr/p185c-neu heterodimeric signaling.

PMID- 8561896
TI  - Loss of the p16/MTS1 tumor suppressor gene causes E2F-mediated deregulation of
      essential enzymes of the DNA precursor metabolism.
AB  - Homozygous deletions of the tumor suppressor gene p16/MTS1 were reported in a
      wide variety of tumors and tumor cell lines. Its product inhibits the
      phosphorylation of the retinoblastoma protein (pRb) by CDK4 and CDK6. Because
      phosphorylation of pRb is a major regulatory event in the activation of the
      transcription factor E2F, a role for p16 in the regulation of E2F-dependent
      transcription was presumed. We investigated the effect of the loss of p16 on E2F
      mediated transcription in a tumor progression model consisting of three cell
      lines originating from a common precursor cell--one p16-positive cell line
      established from the primary biopsy and two lines derived from more advanced
      stages of the tumor representing the same cell clone after loss of p16. We
      observed up- and deregulation of E2F-dependent transcription during the cell
      cycle of the p16-negative cell clones, which returned to normal after transient
      expression of p16. This p16-dependent regulation affects a set of enzymes
      necessary for the activation of all four DNA precursors; it is paralleled by the
      interconversion of transcriptionally active free E2F and transcriptionally
      inactive higher molecular complexes of E2F and is dependent on the existence of
      endogenous pRb. Furthermore, we show that p16-negative cell clones exhibit a
      growth advantage compared to their p16-positive counterparts. One might speculate
      that one feature of tumor progression could be deregulation of E2F-dependent
      transcription caused by loss of p16.

PMID- 8561897
TI  - Transcriptional regulation of the human cholecystokinin gene: composite action of
      upstream stimulatory factor, Sp1, and members of the CREB/ATF-AP-1 family of
      transcription factors.
AB  - We have examined cis-elements and trans-acting factors that regulate
      transcription of the human cholecystokinin (CCK) gene. Transient expression of
      CCK promoter deletion constructs in human SK-N-MC neuroblastoma cells depicted
      positive cis-elements between the positions -100 to -92, -84 to -74, and -58 to 
      37, 5' to the transcription initiation site. Correspondingly, DNase I protection
      analysis showed that transacting factors bound to elements within these regions.
      The sequences encompass a putative basic helix-loop-helix leucine zipper (bHLH
      ZIP) element, an Sp1 element, and a combined cAMP- and TPA-responsive element
      (CRE/TRE) at positions -97 to -92, -39 to -34, and -80 to -73, respectively.
      Mobility and supershift assays demonstrated that upstream stimulatory factor
      (USF) and Sp1 bind to the former elements and competition experiments confirmed
      that CREB/ATF and AP-1 bind to the CRE/TRE element. Mutation of the bHLH-ZIP and
      CRE/TRE elements decreased the activity of the promoter by 65% and 42%,
      respectively. The activity of the promoter was increased six- and two-fold after
      stimulation with forskolin and TPA, respectively. Stimulation was eliminated
      after mutation of the CRE/TRE element. Co-transfection experiments with pRSV-c
      jun, pSV-fos, and pRC-RSV-CREB constructs showed that jun, CREB, and AP-1
      stimulate transcription. We conclude that USF, Sp1, and members of the CREB/ATF
      and AP-1 family of transcription factors are the major determinants of CCK gene
      transcription.

PMID- 8561898
TI  - Characterization of nuclear protein binding sites in the promoter of keratin K17
      gene.
AB  - Keratin K17, while not present in healthy skin, is expressed under various
      pathological conditions, including psoriasis and cutaneous allergic reactions.
      The regulatory circuits involved in transcription of the human keratin K17 gene
      are poorly understood. To begin an analysis of the molecular mechanisms that
      regulate K17 gene transcription, we have studied the interactions between the
      nuclear proteins and the promoter region of the human K17 gene. That promoter
      region comprised 450 bp upstream from the translation initiation site. For these
      studies, we used electrophoretic mobility-shift assays, computer analysis, site
      directed mutagenesis, and DNA-mediated cell transfection. In addition to the
      previously characterized interferon-gamma-responsive elements, we identified
      eight protein binding sites in the promoter. Five of them bind the known
      transcription factors NF1, AP2, and Sp1 and three others bind still unidentified
      proteins. Using site-directed mutagenesis, we have demonstrated the importance of
      the protein binding sites for the promoter function involved in both constitutive
      and interferon-induced expression of the K17 keratin gene.

PMID- 8561899
TI  - Isolation and characterization of four developmentally regulated cathepsin B-like
      cysteine protease genes from the nematode Caenorhabditis elegans.
AB  - Cathepsin B cysteine protease enzymes have been shown to be involved in a variety
      of different biological processes in eukaryotes. We have isolated and
      characterized four distinct cathepsin B-like genes from the genetically tractable
      nematode, Caenorhabditis elegans. This is the first reported finding of a
      cathepsin B-like multigene family within a nonparasitic metazoan. The four genes
      possess distinct genomic architectures, with variations in the position, number,
      and size of introns. The predicted amino acid sequences of the four genes are
      highly diverged. Phylogenetic analysis indicates the divergence of this multigene
      family within C. elegans is as great as the interspecies divergence between the
      vertebrates and nematode cathepsin B-like genes. In addition, each of the four
      genes described here shows a distinct temporal pattern of expression during C.
      elegans development.

PMID- 8561900
TI  - Constitutive amplification of a zinc finger protein gene in cattle.
AB  - The human OZF gene encodes a protein consisting essentially of zinc finger motifs
      of the Kruppel type. Evolutionary studies revealed amplification of the bovine
      OZF gene in cattle. Domestic cattle includes two major subspecies: taurine (Bos
      primigenius taurus) and zebu (B. p. indicus). Amplified sequences were found in
      both subspecies and mapped to the same locus of chromosome X in band q11. No
      amplification was found in other bovids and in particular in Bison, the closest
      related genus to the genus Bos. One copy of the amplified locus was cloned and
      sequenced. It encodes a protein sharing 95% identity with the human OZF protein.
      The bovine OZF gene was detected in an additional locus on chromosome 18 in both
      Bos and Bison, in band q23-24, which is likely to represent the ancestral
      position of the OZF gene. This is the first evidence of gene amplification in a
      mammalian species during evolution.

PMID- 8561901
TI  - Characterization and chromosomal localization of a new protein disulfide
      isomerase, PDIp, highly expressed in human pancreas.
AB  - Protein disulfide isomerase (PDI) catalyzes protein folding and thiol-disulfide
      interchange reactions. The enzyme is localized in the lumen of endoplasmic
      reticulum (ER) and is abundant in secretory cells of various tissues. In this
      study we describe the isolation and characterization from human pancreas of a new
      protein, PDIp, that is structurally and functionally related to PDIs. PDIp cDNA
      is 1,659 bp in length and predicts a protein with an open reading frame of 511
      amino acids. PDIp amino acid sequence shows 46% identity and 66% similarity to
      that of human PDI. PDIp possesses two thioredoxin-like active sites (WCGHCQ and
      WCTHCK) and an endoplasmic reticulum retention signal sequence, KEEL, at the
      carboxyl terminus. Northern analysis of normal human tissues and various human
      tumor cell lines revealed PDIp mRNA (2.0 kb) expression only in the normal
      pancreas. Recombinant PDIp protein catalyzed reductive cleavage of insulin and
      renaturation of reduced RNaseA. Somatic cell genetics and fluorescence in situ
      hybridization localized the PDIp gene to the short arm of human chromosome 16. It
      is concluded that PDIp is a new member of the PDI family and is highly expressed
      in human pancreas.

PMID- 8561902
TI  - Brain microdialysis and its application for the study of animal behaviour.
AB  - Microdialysis is a sampling method that is used to determine the extracellular
      concentration of neurotransmitters in the brain. The method can be applied to
      conscious and unrestrained animals and is very suitable for the study of the
      chemistry of endogenous behaviour. This article reviews the contribution that
      microdialysis made to our understanding of the chemistry of behaviour.
      Methodological and practical considerations such as the implantation time and the
      use of guide cannulas are reviewed. The question whether neurotransmitters and
      related metabolites in dialysates reflect true synaptic release is critically
      discussed. There is much evidence that dopamine, noradrenaline, acetylcholine and
      serotonin in dialysates are related to neurotransmission, but there is serious
      doubt whether this is the case with amino acid transmitters such as GABA,
      glutamate and aspartate. Until now far over 100 papers appeared that used
      microdialysis in behavioural studies. Behavioural activation, the sleep-awake
      cycle and diurnal rhythms were subject of several of these studies. Various
      workers have described neurochemical changes in the brain that are related to
      feeding. Other studies were concerned with sexual behaviour and the sexual cycle
      in females. Parturition, maternal behaviour and offspring recognition have been
      studied in a series of microdialysis studies carried out in sheep. An overview is
      given of the microdialysis studies that were carried out to understand the
      biochemistry of stress. In this respect dopamine and noradrenaline have received
      much attention. A great number of microdialysis studies dealt with the role of
      dopamine in self-stimulation, reward and aversive emotions. It is concluded that
      microdialysis is at presently the most versatile and practical method to study
      the chemistry of behaviour and it is to be expected that it will soon be a
      routine methodology in behavioural research. Finally, perspectives and possible
      future developments of the methods are discussed.

PMID- 8561904
TI  - Processing of visual motion direction in the fronto-parallel plane in the
      stationary or moving observer.
AB  - To examine the effect of concurrent self-motion on the perception of the
      direction of object-motion, random-dot kinematograms were employed in which the
      strength of the directional signal was manipulated by varying the percentage of
      coherently moving pixels. The subject's task was to indicate the motion direction
      of briefly presented displays while undergoing whole body rotations with angular
      accelerations of 0, 5, 15, or 45 degrees/s2. The perception of the direction of
      visual motion in the horizontal plane was impaired only when visual and
      vestibular motion directions were incongruous. The impairment increases with both
      increasing angular acceleration and decreasing percentage of coherently moving
      pixels. For object-motion in the vertical plane, an impairment was found for both
      congruous and incongruous combination of visual and vestibular stimulation,
      although not as pronounced for the latter (i.e., visual upward, vestibular
      downward stimulation, and vice versa). These results are discussed in terms of
      postnatal development and neurophysiological optimization processes resulting
      from intersensory 'updating' through every-day experience of object-motion during
      self-motion.

PMID- 8561903
TI  - Time course of increased vulnerability of cholinergic neurotransmission following
      traumatic brain injury in the rat.
AB  - We have previously shown that spatial memory changes following experimental
      traumatic brain injury (TBI) include long-term changes that are (1) 'overt':
      detected by routine behavioral assessments, or (2) 'covert': undetected in the
      absence of a secondary pharmacological challenge, such as by the cholinergic
      antagonist, scopolamine. Our objective in this study was to extend this finding
      by characterizing the time course of recovery of overt and covert spatial memory
      performance following two magnitudes of experimental TBI. The Morris water maze
      was used to assess cognitive performance. Rats received either moderate magnitude
      (6 m/s, 1.77 mm deformation) or low magnitude (6 m/s, 1 mm deformation) impacts
      through a lateral craniectomy under isoflurane anesthesia. Sham rats underwent
      identical surgical procedures but were not injured. To avoid motor deficits,
      water maze testing started two weeks post-injury. Rats were given four trials per
      day for seven consecutive days. For each trial, latency to find a hidden platform
      was timed. On the sixth, rats were injected (i.p.) with scopolamine (1 mg/kg) 15
      min prior to maze testing. The next day, rats were retested. This testing regimen
      was repeated, beginning 4, 6, and 10 weeks post-TBI. Results showed that, while
      the low-magnitude injury produced no overt spatial memory deficits, the moderate
      magnitude group exhibited overt deficits during the first test regimen. Also,
      while both injury magnitudes produced an enhanced sensitivity to spatial memory
      impairment by scopolamine at two weeks post-TBI, this covert deficit persisted
      only in the severe group at 4, 6, and 10 weeks post-TBI. Qualitative light
      microscopy showed that both injury groups had graded cortical necrosis. However,
      underlying subcortical structures such as the hippocampus appeared intact, with
      no overt cellular or parenchymal damage to the neuropil. These data suggest three
      distinct stages of functional recovery: (1) the initial period when overt
      deficits are present, (2) a period following recovery from overt deficits within
      which covert deficits can be reinstated by a pharmacological challenge, and (3) a
      period following recovery from both overt and covert deficits. Covert deficits
      can persist long after the recovery of overt deficits and, like other
      neurological deficits, the rate of recovery is dependent on the magnitude of TBI.
      Finally, spatial memory deficits can occur in the absence of light microscopic
      evidence of cell death in the hippocampus.

PMID- 8561905
TI  - Effects of D1 and D2 dopamine receptor antagonists and catecholamine depleting
      agents on the locomotor stimulation induced by dizocilpine in mice.
AB  - Low doses of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist
      dizocilpine (MK-801) induce locomotor stimulation in mice, whereas higher doses
      are associated with ataxia, stereotyped behaviors and catalepsy. We investigated
      the role of dopamine receptors and presynaptic dopamine neurons in the locomotor
      effects of dizocilpine. For comparison, we studied several other drugs that
      induce locomotor stimulation in mice. Pretreatment of male mice with haloperidol
      (0.1 mg/kg, i.p.) completely prevented the stimulation of normally coordinated
      locomotion induced by a non-intoxicating dose of dizocilpine (0.1 mg/kg, i.p.);
      haloperidol also attenuated the locomotor stimulation produced by phencyclidine
      (PCP, 1 and 2 mg/kg, i.p.), d-amphetamine (2 and 5 mg/kg, i.p.) and diazepam (0.5
      mg/kg, i.p.). Haloperidol (doses up to 2.5 mg/kg) did not attenuate the ataxia
      and decreased locomotion induced by higher doses of dizocilpine (1 and 2 mg/kg).
      The active cis isomer of flupenthixol (0.5 mg/kg, i.p.), an antagonist of both D1
      and D2 dopamine receptors, also diminished the stimulant actions of all of the
      test drugs, whereas its inactive trans form did not. The selective D1 antagonist
      R(+/-)-SCH 23390 (0.1 mg/kg) and the selective D2 antagonist raclopride (1 mg/kg)
      had little effect on the stimulatory effect of dizocilpine, although they did
      reduce the stimulation produced by PCP, d-amphetamine and diazepam. However,
      pretreatment with a combination of R(+/-)SCH 23390 and raclopride completely
      prevented dizocilpine-induced locomotor stimulation. Pretreatment with alpha
      methyl-p-tyrosine (AMPT, 50 and 250 mg/kg), an inhibitor of tyrosine hydroxylase,
      or with 6-hydroxydopamine (6-OH-DA, 50 micrograms, i.c.v.), a neurotoxin that
      destroys brain dopaminergic and noradrenergic neurons, did not attenuate the
      locomotor stimulation induced by dizocilpine, although these treatments did
      reduce the stimulant effects of d-amphetamine. In AMPT or 6-OH-DA pretreated
      mice, haloperidol (0.125 mg/kg) prevented the stimulatory effect of dizocilpine.
      These results support a role for dopamine receptors in the stimulation of
      normally coordinated locomotion by dizocilpine. However, the locomotor stimulant
      effect of dizocilpine, unlike that of d-amphetamine, can be expressed in the
      presence of D1 or D2 dopamine receptor blockade and does not appear to be
      dependent on intact presynaptic mechanisms.

PMID- 8561906
TI  - Kainic acid decreases hippocampal neuronal number and increases dopamine receptor
      binding in the nucleus accumbens: an animal model of schizophrenia.
AB  - Intracerebroventricular (i.c.v.) administration of kainic acid (KA) produces
      graded neuronal loss in the hippocampus and other regions of the medial temporal
      lobe. Many of these brain regions send excitatory projections to the nucleus
      accumbens, a dopaminergic brain area implicated in psychotomimetic and
      antipsychotic drug action. In the present study, neurochemical function in the
      nucleus accumbens and anterior caudate-putamen was examined one week after i.c.v.
      administration of 1.5, 4.5, or 6.6 nmol of KA. As expected, i.c.v. KA produced
      dose-dependent neuronal loss in the dorsal and ventral hippocampus.
      Extrahippocampal neuronal loss was also observed in the thalamus and piriform
      cortex in some of the KA-treated rats. While ambient levels of dopamine turnover
      and excitatory amino acids in the nucleus accumbens were unaltered by KA,
      administration of the highest KA dose elevated [3H]spiperone binding exclusively
      in the accumbens. Finally, behavioral hyperactivity was observed in KA-treated
      rats over a five-week period following i.c.v. administration. The pattern of
      neuronal loss, receptor upregulation, and behavioral hyperactivity found after
      i.c.v. KA administration may provide a useful animal model of the limbic
      neuropathology and neurochemical dysfunction associated with schizophrenia.

PMID- 8561907
TI  - Unilateral injury of posterior parietal cortex and spatial learning in hooded
      rats.
AB  - The influences of bilateral or unilateral injuries within the posterior parietal
      cortex (PPC) upon spatial learning in a water maze were examined in three
      experiments. Place-learning and response-learning were investigated in a four
      alley 'Greek-cross' shaped water maze with extra-maze visual cues available. No
      differences were detected on any of several measures sensitive to learning
      between the lesion groups on the place-learning task. Microanalysis of behavior
      within trials revealed that animals with either bilateral or right unilateral PPC
      injuries committed significantly more total errors, initial alley entrance
      ('reference memory') errors, and re-entry ('working memory') errors in the
      response-learning paradigm than did either the control or left PPC-injured rats.
      No differences were detected between the latter two groups on these measures.
      Unilateral lesions resulted in asymmetrical placing responses ipsilateral to the
      injury 10 days after surgery whereas bilateral injuries resulted in asymmetrical
      placing with mixed directionality. The acquisition of the response-learning
      problem in the absence of visual cues was studied on animals prepared with
      unilateral lesions and housed post-operatively either in isolation or in a
      'complex environment.' In the absence of visual cues both right and left PPC
      injured rats committed more errors than sham controls, and differential post
      surgical housing did not attenuate these impairments. These same animals were
      trained on the landmark navigation task. Although no differences appeared between
      the lesion groups, a generalized but transient facilitation of learning was
      observed in animals housed in the 'complex' environment. Unilateral injuries
      placed in sham controls failed to disturb retention of the landmark navigation
      strategy. Because none of the PPC-injured animals were deficient in the landmark
      task, a result which is contrary to observations in other laboratories, the
      influence of post-surgical recovery interval upon acquisition of the landmark
      navigation strategy was explored. Animals were prepared with right PPC injuries
      and trained following either a 5 or 35 day recovery interval. Only those animals
      limited to the short recovery interval proved to have a spatial deficit in the
      landmark task. It is concluded that injuries in the PPC of either hemisphere
      disturb egocentric spatial functions. However, animals with left PPC injuries are
      able to compensate by using allocentric visual cues if they are available. It is
      due to the special role played by the right PPC in complex visuospatial functions
      that animals with this injury are unable to compensate.

PMID- 8561908
TI  - Effects of monocular enucleation at birth upon learning of a vertical-horizontal
      discrimination in hooded rats.
AB  - Previously we have demonstrated that adult albino rats with one eye removed at
      birth (OEB) relearn a black-white discrimination faster than those monocularly
      enucleated at maturity (OET) when relearning is conducted after lesioning of the
      visual cortex contralateral to the remaining eye (Type A experiment). This faster
      relearning phenomenon is considered to be one behavioral expression of the
      functioning of the expanded uncrossed visual pathways (expanded UXVPs) resulting
      from monocular enucleation at birth. However, neither OEBs nor OETs were able to
      master the discrimination when the experiment was conducted without previous
      learning following the same surgical treatment (Type B experiment). We
      hypothesized that this occurs because the cues to discriminate might be close to
      the threshold of discrimination for either the normal UXVPs or the expanded
      UXVPs. In order to gain insight into the hypothesis, the present study was
      undertaken using hooded rats as subjects which genetically possess larger and
      presumably more efficient functioning UXVPs. The questions addressed were as
      follows: 1) Whether or not the UXVPs can mediate a vertical-horizontal
      discrimination in OEBs and OETs. 2) If they can, is there any difference in the
      upper limit of discrimination capacity between the normal UXVPs and the expanded
      UXVPs? Three experiments were carried out. In the Type A experiment OEBs
      relearned discrimination of the 10-mm stripes [0.44 cycles/degree (c/d)] faster
      than OETs (Experiment 1), yet in the Type B experiment neither OEBs nor OETs were
      capable of acquiring that discrimination (Experiment 2). However, they could
      originally master the discrimination equally well when the width of stripes was
      broadened to 30 mm (0.15 c/d). And when the width of stripes was systematically
      reduced thereafter, the width of the smallest stripes for the expanded UXVPs to
      discriminate was found to be 6 mm (0.73 c/d) and that for the normal UXVPs 10 mm
      (0.44 c/d) [Experiment 3]. These findings were discussed in relation to the
      hypothesis advanced on our previous data in albino rats.

PMID- 8561909
TI  - Effects of postnatal stimulation on the passive avoidance behaviour of young
      rats.
AB  - We examined the effects of stimulation on either postnatal days 1-7 or 21-27 on
      passive avoidance reaction (PAR) of young rats. Animals received tactile or
      visual stimulation for 10 min each day, and were trained on postnatal day 28 in a
      step-through apparatus using a footshock of 0.75 mA for 2 s. Retention was tested
      on five consecutive days beginning on day 29. Memory retention was measured for
      each rat 24, 48, 72, 96 and 120 h after the acquisition trial. Step-through
      latencies to enter the dark compartment, time spent in the illuminated
      compartment and number of crossings of the light beam were recorded up to 200 s.
      Rats that received tactile or visual stimulation during the 4th postnatal week
      displayed significantly lower PAR latencies, a shorter stay in the illuminated
      compartment and a higher number of crossings of the light beam compared to rats
      treated during the 1st postnatal week. The untreated control group showed a rapid
      decline of PAR latencies. All experimental groups remained in the illuminated
      compartment longer and showed PAR latencies well above those of the control
      group. The differences became more pronounced when visual stimulation in the
      first postnatal week was used. The number of crossings of the light beam was
      significantly reduced by the treatment, with the exception of the experimental
      group stimulated visually in the 4th week. The behavioural changes induced by
      tactile or visual stimulation have a long-lasting effect in coping with a
      stressful task.

PMID- 8561910
TI  - Calpain: novel family members, activation, and physiologic function.
AB  - The current status of calpain research is summarized on the basis of the most
      recent results. The main points are as follows. (i) Calpain constitutes a large
      family. (ii) Ca2+ ions cause the dissociation of calpain into subunits and the
      resulting free 80 kDa subunit is the active form of the enzyme. This dissociation
      corresponds to the activation of calpain. (iii) Some powerful clues have been
      obtained that will be helpful for analyzing the physiological function.

PMID- 8561911
TI  - Characterization of N-linked carbohydrate chains of the crayfish, Astacus
      leptodactylus hemocyanin.
AB  - The primary structure of the carbohydrate chains of hemocyanin from the crayfish
      Astacus leptodactylus were investigated. The carbohydrate content is 0.2% (w/w)
      as referred to total hemocyanin content, resp. 1.8% as referred only to the one
      subunit which is glycosylated. Mannose and N-acetylglucosamine are present in a
      molar ratio of 6:2. The carbohydrate chains are N-glycosidically linked as
      revealed by dot blot analysis using various lectins and enzymatic
      deglycosylation. Furthermore, they are part of only one hemocyanin subunit of A.
      leptodactylus. After enzymatic deglycosylation with PNGase F, the oligosaccharide
      pool was separated by FPLC on Mono Q and subsequent HPLC on Lichrosorb-NH2, the
      subfractions were characterized by 1H NMR spectroscopy. A total of six
      oligosaccharides, ranging from Man4GlcNAc2 to Man9GlcNAc2 is present, Man6GlcNAc2
      representing the most abundant one with 57% of all oligosaccharides.

PMID- 8561912
TI  - Atrial-natriuretic-peptide receptors in glomerular cryosections of renal
      malignant and spontaneously hypertensive rats.
AB  - ANP-receptors affinities (KD) and capacities (Bmax) were assayed in cryosections
      of glomeruli from 'malignant' hypertensive rats (2K-1C) and spontaneously
      hypertensive rats (PHR). Plasma ANP concentration was twofold higher in 2K-1C (P
      < 0.05) and PHR (P < 0.02) than in the respective controls, KD and Bmax for
      rANP99-126 and ANP103-123 did not differ. ANP mediated cGAMP release in 2K-1C
      rats was also unaffected. ANP-C glomerular receptors (i.e. displacement of tracer
      binding with ANP103-123) were not down-regulated and had unchanged peptide
      binding affinity in either kidney of rats with 'malignant' hypertension and in
      PHR. The difference between Bmax for rANP99-126 and Bmax for rANP103-123 (ANP-A
      receptor binding) indicates moderate up-regulation of ANP-A receptors in the
      clipped, and down-regulation in the contralateral kidney of 2K-1C (2K-1C, right
      vs. left, P < 0.05). Since [ANP]pl, and also Bmax and KD for ANP were similar in
      both hypertension models investigated, changes of the [ANP]pl/ANP-receptor system
      can not completely explain the marked natriuresis of rats with 'malignant'
      hypertension.

PMID- 8561913
TI  - Evidence of the coevolution of a snake toxin and its endogenous antitoxin
      cloning, sequence and expression of a serum albumin cDNA of the Chinese cobra.
AB  - A full-length cDNA of the serum albumin (CSA) of the cobra (Naja naja kaouthia)
      was cloned from a lambda gt 11 library. It encodes a mature protein of 614 amino
      acid residues homologous to the precursor of mammalian serum albumins. The 1
      degree and 2 degrees structures of the CSA resemble those of the human variety.
      The putative toxin binding sites are mainly located in the subdomains IIA and
      IIIA. The relation between structural homology and function of the serum albumins
      (SA) is discussed. An analysis of their evolutionary tree revealed that anti
      toxicity arose by < 90 amino-acid exchanges. The rate of substitution is much
      higher in the SA than in cytochrome C, which probably reflects the difference in
      evolutionary driving forces. The evolutionary period of the SA (6.7 +/- 0.1 M.Y.)
      significantly exceeds that of hemoglobin (5.8 M.Y.). Eight tripeptides in the
      nicotinic acetylcholine receptor (ACR), all flanking the putative toxin binding
      site, are also found in the CSA where they join to form 1 octa-, 1 penta- and 4
      tripeptides, thus indicating the concerted evolution of two functionally linked
      proteins: toxin and antitoxin (CSA).

PMID- 8561914
TI  - Identification of human nonpancreatic-type ribonuclease by antibodies obtained
      against a synthetic peptide.
AB  - An antibody that recognizes human nonpancreatic-type ribonuclease was obtained by
      immunizing a rabbit with a 14-residue synthetic peptide corresponding to the N
      terminal sequence of eosinophil-derived neurotoxin which is identical to human
      liver ribonuclease. This amino acid sequence is unique to this protein. The anti
      N-peptide antibody was purified by protein A-Sepharose and by using ELISA and SDS
      PAGE immunoblot techniques, the antibody reactivity against EDN and partially
      purified nonpancreatic-type ribonucleases from human plasma and urine was
      observed. Cross-reactivity with bovine pancreatic ribonuclease A and other
      proteins was not detected. In addition, the activity of the nonpancreatic-type
      ribonuclease was not affected by the antibody. The immune response was elicited
      without the need for a carrier protein showing that the N-terminal sequence of
      nonpancreatic ribonuclease contains a specific epitope. This antibody can be used
      for the immunological identification of both the native and denatured forms of
      this type of enzyme.

PMID- 8561915
TI  - Structural and immunological studies on the soluble formate dehydrogenase from
      Alcaligenes eutrophus.
AB  - During growth with formate as the sole energy source the autotrophic bacterium
      Alcaligenes eutrophus synthesizes a cytoplasmic formate dehydrogenase. The enzyme
      is a molybdo-iron-sulfur-flavo protein and the major NADH-producing system under
      these growth conditions, although it was estimated to constitute only 0.65% of
      the soluble cell protein. An electron microscopic analysis of the purified enzyme
      revealed that the particle is made up of four nonidentical submasses,
      corroborating previous structural data. The NH2-terminal amino acid sequences of
      the enzyme subunits exhibited significant similarities to those of only one other
      heteromeric formate dehydrogenase, the enzyme from the methane-utilizing
      bacterium Methylosinus trichosporium. Metal analyses yielded 21.5 g-atom iron,
      2.18 g-atom nickel, 0.76 g-atom molybdenum, and 0.59 g-atom zinc per mol of
      enzyme. Initial electron paramagnetic resonance spectroscopic studies showed at
      least three distinct signals which appeared upon reduction of the enzyme with
      NADH or formate. The corresponding spin systems could be attributed to iron
      sulfur centers of the enzyme. Comparative immunostaining and activity-staining
      experiments using cell extracts from various bacteria established immunological
      similarities between the soluble formate dehydrogenase of A. eutrophus and the
      soluble enzymes from all tested facultative autotrophs as well as from M.
      trichosporium.

PMID- 8561916
TI  - Diversity in the properties of two sialidase isoenzymes produced by Clostridium
      perfringens spp.
AB  - Clostridium perfringens produces two sialidases, one of which has a molecular
      mass of 71 kDa and is secreted, while the 'small', 43 kDa isoenzyme remains in
      the cells. The secreted, higher molecular mass sialidases of two different
      clostridial strains, DSM756T and A99, exhibit maximum activity at pH 5.5 and at
      51 or 55 degrees C, respectively. The molecular mass of both enzymes is 71 kDa in
      SDS-PAGE and 63 kDa as determined by gel-filtration, which indicates the absence
      of subunits. Natural sialidase substrates are hydrolyzed at comparably high
      rates, e.g. the glycoproteins fetuin and bovine submandibular gland mucin, the
      homopolymer colominic acid, and the ganglioside mixture from bovine brain. The
      partially purified 'small' isoenzyme from C. perfringens A99 cells had similar
      properties to the corresponding recombinant sialidase isolated from the
      Escherichia coli host. It is located inside the clostridial and E. coli cells and
      exhibits maximum activity at pH 6.1 and 37 degrees C. A relative molecular mass
      of 32,000 was found with FPLC gel-filtration chromatography, while primary
      structure analysis yielded a value of 43,000. It differs a significantly from the
      'large' isoenzyme by substrate specificity. Preferred substrates are
      oligosaccharides, while other, more complex sialoglycoconjugates are hydrolyzed
      only at very low rates. alpha 2,3-linkages are hydrolyzed much faster than alpha
      2,6-bonds.

PMID- 8561917
TI  - Kinetic analysis of an autocatalytic process coupled to a reversible inhibition:
      the inhibition of the system trypsinogen-trypsin by p-aminobenzamidine.
AB  - A kinetic analysis of the mechanism of autocatalytic activation in the presence
      of a reversible inhibitor is presented. The kinetic equations of both the
      transient phase and the steady state are derived for this mechanism. We have
      extended the kinetic equations derived to a particular case in rapid equilibrium
      conditions. This analysis is illustrated by the experimental study of the
      inhibition by p-aminobenzamidine of trypsin activity in its action on
      trypsinogen. In such system, the amount of active enzyme increases exponentially,
      as expected from an autocatalytic process. The results obtained show that the
      apparent activation rate constant decreases non-linearly with the initial
      concentration of inhibitor, according to the equations obtained in the kinetic
      analysis.

PMID- 8561918
TI  - Studies on human dietary requirements and safe range of dietary intakes of
      selenium in China and their application in the prevention of related endemic
      diseases.
AB  - The human dietary selenium requirement in China has been estimated by various
      methods. The minimum dietary selenium requirement for the prevention of Keshan
      disease (KD) was found to be around 17 micrograms/d. On the other hand, an intake
      of 40 micrograms/d is required to maintain the plasma glutathione peroxidase
      (GPx) activity at plateau. Hence 40 micrograms/d is considered as the adequate
      dietary selenium requirement. Studies conducted in a chronic selenosis area
      indicate that the toxic dietary selenium intake (adverse effect level), which
      would maintain the characteristic fingernail changes, was approximately 1600
      micrograms/d. The mean value of dietary selenium intakes, which enabled the five
      patients to recover from fingernail lesions, was found to be 819 +/- 126
      micrograms/d. At a 95% confidence limit, the lower limit is around 600
      micrograms/d. Therefore, 600 and 400 micrograms/d were suggested as the
      individual daily maximum safe selenium intake and the safe dietary selenium
      intake, respectively. The results were used in the prevention of Se-related
      endemic KD and Kashin-Beck disease (KBD).

PMID- 8561919
TI  - Role of certain environmental factors on cadmium uptake and toxicity in Spirodela
      polyrhiza (L.) Schleid. and Azolla pinnata R. Br.
AB  - Effects of pH, temperature, EDTA and photosynthetically available radiation on
      the uptake and toxicity of Cd was investigated in Spirodela polyrhiza (L.)
      Schleid. and Azolla pinnata R. Br. In general, Cd toxicity was accentuated in
      conditions which favoured enhanced intracellular Cd uptake. Extracellular binding
      and intracellular uptake of Cd were lowered at pH values > 7 due to reduced
      availability of the aquo ion; consequently, toxicity was markedly reduced. At pH
      value < 7, extracellular binding remained unaffected, although intracellular
      uptake and toxicity of Cd were enhanced. This perhaps resulted from changes in
      membrane permeability as extracellular Cd binding was not affected by the decline
      in pH from 7 to 4. Moreover, speciation of Cd is known to remain unchanged
      throughout this pH range as most of the Cd (> 99%) remains available as the aquo
      ion. The presence of EDTA in the medium decreased extracellular binding,
      intracellular uptake and toxicity of Cd in test plants. This was due to formation
      of Cd-EDTA complex which was obviously not available to test plants. Elevation of
      temperature increased intracellular Cd uptake and this resulted in enhanced toxic
      effects. Similarly, increase in photosynthetically available radiation caused a
      slight increase in Cd uptake and toxicity in test plants. Obviously, rise in
      temperature or PAR increased metabolic activities of test plants thereby leading
      to increased Cd transport and toxicity.

PMID- 8561920
TI  - Prevention and treatment of pneumoconiosis in China.
AB  - Silicosis is one of the most serious occupational diseases which affect many
      workers' health in China. Under the guidance of policies from the Chinese
      Government, the industries, health care institutions, scientists and workers were
      organized and have made great efforts in prevention and treatment of silicosis as
      well as pneumoconiosis. Since the 1960s, the national health standards and chest
      X-ray diagnosis criteria for silicosis were established and have been revised
      recently. A nationwide epidemiological survey revealed that the cumulative
      pneumoconiosis cases were about 4,800,000 (1949-1992). The high prevalence rate
      has been the motivation to search for anti-silicotic drugs. Several kinds of anti
      silicotic drugs were studied and found to be able to retard progression of
      silicosis and cause changes in X-ray picture. The mechanism of drug efficiency
      and the development of silicosis have attracted the interest of scientists in
      this fields and fruitful results have been obtained. For prevention of dust
      hazards, the systematic design for facilities of dust collection and the
      isolation of dust source appropriate to township industries have been worked out
      and used widely. Recently, under the supervision of the Ministry of Public
      Health, China, a pilot study on counter-measure for industrial hazards and health
      care service in township industries has been instituted.

PMID- 8561922
TI  - Melanophore indexing: a new bio-assay technique for the analysis of acute heavy
      metal (HgCl2) toxicity.
AB  - Toxicity of 0.3 ppm (96 h LC50 value) and 0.03 ppm of mercuric chloride on the
      melanophores of the skin at different time intervals has been studied. Mercury
      treatment causes immediate increase in the number and size of the pigment cells.
      Subsequently these pigment cells form a dense matting of melanophore network with
      their cell processes interlacing with those of their neighbours. These cells
      later show degeneration and lysis releasing large quantity of pigment granules
      into the intercellular spaces in the dermis. Later the pigment cells regenerate
      several times each followed by degeneration in a cyclic manner. Prolonged
      treatment with sublethal concentration of mercuric chloride does not show
      significant alteration in the melanophore density and size. Statistical analysis
      and wide spread destruction of melanophores observed during 4-6 days of exposure
      might help in testing water samples contaminated with lethal concentration of
      heavy metal salts.

PMID- 8561921
TI  - Late protective effects of the anticalmodulin drug fluphenazine on carbon
      tetrachloride-induced liver necrosis.
AB  - Fluphenazine (FP) treatment (50 mg/kg bw, ip in saline) 30 min before or 6 or 10
      h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the
      liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on
      the covalent binding of CCl4 reactive metabolites to cellular constituents and on
      CCl4 induced lipid peroxidation. FP lowered body temperature of the CCl4-poisoned
      animals during the 24 h observation period. The obtained results are compatible
      but do not prove the hypothesis that calmodulin (CaM) had participation in late
      occurring events preceding necrosis. FP lowering action on body temperature,
      however, might also play a role in the effects of this drug on the onset of CCl4
      induced liver necrosis. FP levels in liver tissue as determined by gas
      chromatography-mass spectrometry evidenced the presence of the drug in amounts
      sufficient to inhibit CaM and that suggests that not all preventive effects of FP
      are due to its indirect actions on the central nervous system via decreased body
      temperature.

PMID- 8561923
TI  - Biomonitoring of anticholinesterase pesticides in the soil: usefulness of soil
      Collembola.
AB  - The impact of Methyl parathion and Carbaryl was evaluated on an ecologically
      important soil Collembola, Cyphoderus sp. Enzyme characteristics demonstrate
      substrate optimum at 1 10(-2) mol/L temperature optimum at 30 degrees C with a pH
      requirement of 8.0. In vivo inhibition of whole body AChE reveals higher degree
      of inhibition by LD50 dose of Methyl parathion as compared to that of Carbaryl
      where maximum inhibition was noticed at the agricultural dose.

PMID- 8561924
TI  - Study on the mutagenicity of diesel exhaust particles.
AB  - The mutagenicity of diesel exhaust particles (DEP) was studied by using
      Salmonella typhimurium strains TA98 and TA100 in vitro and mice micronucleus in
      vivo test. DEP from six kinds of medium and heavy-duty diesel vehicles, which
      were made in China and imported, were tested. The vehicles were operated under
      free accelerating condition. The results showed that the DEP contained mutagenic
      activity. An increase in the number of the Salmonella TA98 was observed in the
      presence and especially in the absence of S9 mix. Positive results were also
      obtained from mice micronucleus assay. The frequency of mice bone marrow
      micronucleated polychromatic erythrocytes (M PCE) was increased and it showed a
      definite dose-response relationship. Comparing the different types of the
      vehicles, we found that the mutagenicity of DEP from domestic made vehicles was
      stronger than that from the imported ones.

PMID- 8561925
TI  - Ceruloplasmin or fibronectin synergism with quartz dust on stimulating collagen
      gene transcription in human 2BS fibroblast.
AB  - Human alpha 1(I), alpha 2(I) and alpha 1(III) cDNA probes and RNA dot
      hybridization were employed to quantitate collagen mRNA changes after adding
      silica dust into the media of human 2BS fibroblasts. At all dosages used (100,
      200, 500 and 1000 micrograms), the alpha 1(I), alpha 2(I) and alpha 1(III) mRNA
      levels increased one day after dusting. At the same dosage of silica (100
      micrograms), alpha 1(III) mRNA increased earlier than type I collagen mRNA did.
      The type I and type III collagen mRNA contents in the experimental groups were
      higher than those in control on days 3, 5, 7 and 9. The effect of ceruloplasmin
      (Cp) and fibronectin (Fn) on collagen mRNA synthesis was also studied, after
      adding silica dust, Cp or Fn into the media of human 2BS fibroblast. The results
      showed that Cp and Fn have stimulating effect on collagen mRNA production. When
      both Cp and silica dust were added into cell culture media, the collagen mRNA
      level was increased more than those of adding either Cp or silica dust alone.
      Similar situations were found for Fn. Cp (or Fn) synergism with silica dust on
      stimulating transcription of human collagen gene was suggested.

PMID- 8561926
TI  - Toxicity evaluation of in vitro cultures of freshwater cyanobacterium Microcystis
      aeruginosa: I. Hepatotoxic and histopathological effects in rats.
AB  - Laboratory cultures of freshwater cyanobacterium (blue-green alga) Microcystic
      aeruginosa PCC 7806 was evaluated for its hepatotoxic effects in rats. The
      lyophilized cell extract injected intraperitoneally at 1 and 2 LD50 (15.8 and
      31.6 mg/kg, respectively) produced significant increase in liver-specific enzymes
      viz. plasma alkaline phosphatase, gamma-glutamyl transferase, lactate
      dehydrogenase with a concomitant decrease in hepatic glutamic pyruvic
      transaminase. A corresponding increase in liver body weight index and
      histopathological changes in liver (degeneration of hepatocytes, congestion and
      hemorrhage etc.) are indicative of a dose and time dependent hepatotoxic nature
      of the algal extract.

PMID- 8561927
TI  - A biochemical study on combined treatment of experimental silicosis with
      tetradrine-PVNO and tetradrine-QOHP in rats.
AB  - A better understanding is needed to explain the mechanism of therapeutic effect
      of combined use of tetradrine-PVNO and tetradrine-QOHP which play very important
      roles in treatment of silicosis. Blood prolidase (PLD), monamine oxidase (MAO)
      and plasminogen (PLG) in silicotic rats after treatment with tetradrine-PVNO or
      tetradrine-QOHP were measured. The values obtained were compared with the
      untreated silicotic rats. It was found that the silicotic rats that received
      tetradrine-PVNO showed significant increase in PLD and decrease in PLG, but no
      significant change in MAO. The PLD in plasma of silicotic rats that received
      tetradrine-QOHP were elevated significantly, but PLG and MAO did not change
      appreciably. These findings suggest that the combined use of tetradrine-PVNO and
      tetradrine-QOHP can accelerate the degradation of collagen in silicotic rats.

PMID- 8561929
TI  - Brain stem surgery.

PMID- 8561928
TI  - Role of oxidative stress in non-genotoxic carcinogenesis with special reference
      to liver tumors induced by peroxisome proliferators.
AB  - Peroxisome proliferators (POPs), such as hypolipidemic drugs or industrial
      phthalate ester plasticizers, are widely known as non-genotoxic hepatocarcinogens
      in rodents. As one of the possible mechanisms of POP-induced carcinogenesis, the
      "Oxidative Stress" theory has been postulated. In this review, in order to
      reconsider the significance of "Oxidative Stress" to POP-induced carcinogenesis,
      we focus on in vivo studies examining formation of 8-hydroxydeoxyguanosine (8-OH
      dG), a marker of oxidative DNA damage with mutagenic potential, after treatment
      of rodents with POPs. Some studies clearly demonstrated that 8-OH-dG levels in
      the liver DNA were increased by POP-treatments. These findings suggest that
      "Oxidative Stress" could contribute as one factor to POP-induced carcinogenesis.
      Furthermore, we refer to other multiple biological changes caused by POP
      treatment presumably contributing to the carcinogenic mechanisms, and consider
      possible roles of "Oxidative Stress" in the carcinogenesis process.

PMID- 8561930
TI  - Endosaccular treatment of inoperable intracranial aneurysms with platinum coils.
AB  - Endosaccular packing of inoperable aneurysms with electrolytic platinum coils was
      performed in 50 patients. Complete embolization of the aneurysms was achieved in
      100% of small, 95% of large and 85% of giant aneurysms, with combined procedural
      and periprocedural morbidity and mortality rates of 6 and 4%, respectively.
      Follow-up angiography of 42 aneurysms demonstrated some degree of refilling in
      17% of small, 19% of large and 50% of giant aneurysms. The risks associated with
      the procedure were similar in aneurysms of the carotid and vertebrobasilar
      circulations. This treatment should therefore be considered for all inoperable
      aneurysms and particularly for aneurysms involving the posterior circulation. Its
      long-term efficacy remains uncertain.

PMID- 8561931
TI  - Interstitial iodine-125 radiosurgery for cerebral metastases.
AB  - The current study evaluates the efficacy of interstitial 125-iodine radiosurgery
      (brachytherapy) in 93 patients with circumscribed, spherical, mostly solitary
      metastases. In all patients the histological diagnosis was established by
      stereotactic biopsy. The treatment results of three therapeutic regimens have
      been examined retrospectively: Group A (38 patients) had interstitial
      radiosurgery with a reference tumour dose of 60 Gy in combination with
      percutaneous radiotherapy (40 Gy). Group B (34 patients) was treated by
      interstitial radiosurgery alone (reference dose 60 Gy). Group C (21 patients with
      recurrent metastases after previous radiotherapy/surgery) was treated by
      interstitial radiosurgery alone (reference dose 60 Gy). Median survival after
      interstitial radiosurgery was 17 months in group A, 15 months in group B, 6
      months in group C. Favourable prognostic factors were a Karnofsky performance
      rating > or = 70, solitary metastasis, absence of disseminated disease, and a
      time interval > 1 year between diagnosis of the primary tumour and diagnosis of
      the cerebral metastases. Interstitial radiosurgery plus percutaneous radiotherapy
      did not prove to be superior to interstitial radiosurgery alone. No patient died
      of a locally irradiated metastasis. We conclude that interstitial radiosurgery
      achieves control of the growth of solitary spherical cerebral metastases in any
      location without radiation toxicity.

PMID- 8561932
TI  - Swallowing performance following anterior cervical spine surgery.
AB  - The aim of this study was to assess the incidence and severity of dysphagia
      following anterior cervical spine surgery for cervical spondylosis. One-hundred
      patients were contacted 12-22 months following cervical spine surgery. Those
      reporting persistent swallowing impairment were invited to attend for further
      investigation. Of 73 respondents, 33 (45%) experienced postoperative dysphagia.
      This persisted for longer than 6 months in nine (12% of respondents). Of five
      subjects attending for investigation, none had a definite radiological
      abnormality. In contrast, manometry suggested hyperactivity of the pharyngo
      oesophageal segment in these patients, although with normal co-ordination.
      Surgeons should warn of the risk of transient dysphagia in 45% of patients
      postoperatively and of its persistence in around 10%. Radiological examination
      may be normal and manometry is the investigation of choice. Persistent, severe
      dysphagia may be ameliorated by cricopharyngeal myotomy or pharyngeal dilatation.

PMID- 8561933
TI  - Medulloblastoma: factors influencing the educational potential of surviving
      children.
AB  - Twenty-five children with a histological diagnosis of medulloblastoma operated
      upon in our unit and who had then been treated with identical radiotherapy
      regimes were studied in an attempt to determine the academic potential of
      children who survive for more than two years following their initial
      presentation. Fourteen children were attending a mainstream school at which they
      required no special help or remedial classes and were in the appropriate year for
      their age while eleven required special help with their schooling. Seven of these
      attended a mainstream school, but required remedial classes for help with
      reading, writing and arithmetic while two were in a class a year below what would
      have normally been expected for their age group. Two children attended a special
      school for children with learning difficulties. These differences in academic
      potential can be related to the age of the child at presentation and the presence
      or absence of postoperative complications.

PMID- 8561934
TI  - Treatment of chronic subdural haematoma with burr-hole craniostomy and closed
      drainage.
AB  - Despite the high incidence of chronic subdural haematoma (SDH), to date
      relatively few authors have undertaken a systematic analysis of the results
      attained following burr-hole craniostomy and closed-system drainage on the basis
      of a study involving a large patient population defined according to clear-cut
      criteria. Between 1980 and 1993, surgery was performed on 212 patients with a
      chronic SDH. In a retrospective study, the condition of each patient was assessed
      at the time of admission on the basis of the Bender Scale and the results 4 weeks
      after discharge were classified according to the Glasgow Outcome Scale (GOS). At
      admission, 165 patients (78%) were in a satisfactory condition (Stage 1 or 2); 47
      (22%) were at Stage 3 or 4, i.e. stuporous or comatose. Nine (4%) of the patients
      died; none of these deaths was attributable to the operation. In addition to
      significant extracerebral disease (2.4%), CT revealed ischaemic cerebral
      infarctions in three patients (1.4%) after removal of the SDH. The operative
      morbidity was 4.2%. In 22% of the patients, surgical intervention was required to
      remove a recurring SDH. In 90% of the patients, the results achieved could be
      graded as 'very good' or 'good' (GOS 1 or 2). The results were related to the
      condition at admission (p < 0.001) and the patient's age (p < 0.05). Factors that
      did not have a significant effect on the outcome included whether the SDH
      formation was bilateral or unilateral, the extent of neomembranous organization
      of the haematoma, and the amount of primary cerebral expansion following
      decompression. We were able to confirm the results of previous studies that the
      method used is a highly effective treatment, with a low incidence of
      complications.

PMID- 8561935
TI  - Intracranial meningiomas following irradiation--a growing problem?
AB  - We present 10 cases of meningiomas occurring after high-dose irradiation for
      other brain tumours. These constitute 3.7% of 272 patients with meningiomas
      treated in our unit over 10 years. The clinical and pathological features of the
      10 cases were added to those of 69 previous cases documented in the literature
      and compared with the features of our 262 spontaneous meningiomas. The literature
      on 119 cases of low-dose radiation-induced meningiomas was also reviewed.
      Malignant histological features and multiplicity were more common in the
      radiation-induced meningiomas (p < 0.01). Increasing long-term survival rates
      following radiotherapy for primary intracranial tumours, particularly in
      childhood, may lead to an increased incidence of postirradiation meningiomas.

PMID- 8561936
TI  - Physical properties of cerebrospinal fluid of relevance to shunt function. 1: The
      effect of protein upon CSF viscosity.
AB  - Viscosity is the resistance to flow of a fluid and it is the only property of a
      fluid that will affect its flow through a system of valveless tubing (surface
      tension will affect the opening and closing of valves that are included in the
      system). The effect that an elevated protein concentration has upon CSF viscosity
      has received little study, yet many neurosurgeons believe that CSF with an
      elevated protein content is too viscous to flow satisfactorily through shunts.
      The total protein content and viscosity of 126 specimens of CSF from
      hydrocephalic patients were measured and analysed with reference to the aetiology
      of the hydrocephalus. The results indicate that high protein concentrations do
      not greatly affect the viscosity of CSF, and that the aetiology is also of little
      consequence. These findings were highly significant on linear regression analysis
      (p < 0.001). The flow of the most viscous CSF that is likely to be encountered
      would be reduced by only 7% through a given catheter, compared with that of the
      least viscous CSF.

PMID- 8561937
TI  - Physical properties of cerebrospinal fluid of relevance to shunt function. 2: The
      effect of protein upon CSF surface tension and contact angle.
AB  - CSF surface tension has received little study, and yet it will effect the
      pressure at which shunt valves operate, and by influencing the degree of
      hydrophobicity (contact angle) will alter the attraction between bacteria and
      neurosurgical prostheses. A study is therefore presented of the effect of protein
      content upon the surface tension of CSF and its contact angle to silicone rubber.
      Both of these quantities fell throughout the normal range of CSF protein, but
      above 1 g/l, additional protein had little effect, and the results obtained were
      similar to that reported for plasma. The effect of surface tension on the opening
      and closing pressures of hydrocephalus shunt valves and of contact angle in the
      adhesion of bacteria to neurosurgical implants is discussed.

PMID- 8561938
TI  - The effect of tumour associated epilepsy on performance/handicap scales used in
      cerebral glioma.
AB  - The sensitivity of three scales of performance and handicap to the presence and
      development of epilepsy in patients with brain tumours was studied. Two
      hypothetical cases had equivalent disability, in one case due to epilepsy and in
      the other to physical impairment. The second case later developed epilepsy. All
      consultant neurologists and neurosurgeons in Scotland were asked to grade the
      cases using three scales commonly used for patients with cerebral glioma.
      Consultants rated the patient with epilepsy alone as being less disabled and
      handicapped than the patient with physical impairment without seizures (sign test
      p < 0.003). At best 21% of clinicians (p = 0.03) were able to report a change in
      performance score in the second case when seizures developed. These scales do not
      reflect changes in handicap and performance associated with tumour associated
      epilepsy. Clinical trial protocols for treatments for brain tumours must state
      how performance and handicap related to epilepsy will be measured.

PMID- 8561939
TI  - Adult postrepair myelomeningocoele and tethered cord syndrome: good surgical
      outcome after abrupt neurological decline.
AB  - Adults who have had repair of an open myelomeningocoele at birth are susceptible
      to a variant of adult onset tethered cord syndrome (ATCS). Precipitous and
      profound loss of lower extremity motor function occurred in two postrepair adult
      patients, but was not seen in any of our 12 cases of adult tethered cord with any
      other aetiologies. Both postrepair ATCS patients made a good recovery after
      surgical release of the tether. For the patients with other aetiologies, surgery
      yielded improvement or recovery of urinary continence in 57%, relief from pain in
      78% and improved strength in 80%. Evidence of retethering was observed in 25% of
      the operated patients at intervals ranging from 1 to 9 years postoperatively. We
      conclude that surgical release of tether can reverse incontinence in ATCS of any
      aetiology and that in the post-myelomeningocoele repair patient, both
      dexamethasone and surgical intervention are helpful in reversing acute
      neurological deterioration.

PMID- 8561940
TI  - Long vascular pedicle cranial flap.
AB  - Two case reports illustrate a long vascular pedicle cranial bone flap. A split or
      full thickness skull bone flap is based on the pericranium layer. The temporalis
      muscle with its overlying fascial layers and vascular pedicles form the base of
      this flap and assure its adequate vascularization. The technique and its uses in
      the reconstruction of calvarial defects is discussed.

PMID- 8561941
TI  - Cervical myelopathy caused by an intracranial dural arteriovenous fistula.
AB  - We report a case of progressive myelopathy in a 50-year-old lady with an
      intracranial dural arteriovenous fistula. Transcatheter embolization followed by
      surgical resection of the intracranial fistula resulted in reversal of the
      myelopathy. The diagnosis and management of this potentially reversible condition
      is discussed and the literature reviewed.

PMID- 8561942
TI  - Arachnoid cyst within the fourth ventricle--a case report.
AB  - We describe a case of congenital intra-fourth ventricular arachnoid cyst and
      review the literature. A one-and-half-year-old boy had presented with delayed
      milestones, intermittent raised intracranial pressure and ataxia. Excision of the
      arachnoid cyst has cured him.

PMID- 8561943
TI  - Teeth in the cerebellopontine angle: an unusual dermoid tumour.
AB  - An hour-glass-shaped multidensity lesion found by CT in a 6-year-old boy who had
      been admitted to the emergency department after a mild car accident. This lesion
      turned out to be a congenital dermoid tumour of the right cerebellopontine angle
      tentorial notch region containing 12 mature teeth and 14 pseudocarilagenous
      structures. This is the first case of dermoid tumour containing so many teeth,
      reported in an asymptomatic person and located off the midline.

PMID- 8561944
TI  - Posttraumatic cerebellar infarction.
AB  - We report an 18-year-old patient who presented with delayed neurological
      deterioration secondary to posttraumatic cerebellar infarction. Management by
      ventricular drainage and posterior fossa decompression resulted in a good
      outcome. The absence of a demonstrable structural vascular lesion makes this case
      apparently unique. The possible aetiology, pathogenesis and management of this
      condition are discussed.

PMID- 8561945
TI  - Intracerebellar melanotic schwannoma: a case report.
AB  - Neuro-axial melanotic schwannoma is a rare entity. We report the clinical, CT and
      pathological features of a solitary, cellular intracerebellar melanocytic
      schwannoma in a 65-year-old woman. The probable origin of this type of tumour is
      discussed.

PMID- 8561946
TI  - 'Angiogliomas' or 'angiomatous gliomas' a report of two patients and review of
      the literature.

PMID- 8561947
TI  - De novo development of saccular aneurysms: report of two cases.
AB  - The development of de novo aneurysms after previous successfully treated
      aneurysms is uncommon. If risk factors are not present the patient may be
      reassured that the risk of developing a further aneurysm following successful
      treatment is minimal. Two cases of second aneurysms developing six and eighteen
      years after successful treatment of a first aneurysm are reported. The risk
      factors associated with the formation of second aneurysms are emphasized.

PMID- 8561948
TI  - Dural repair.

PMID- 8561949
TI  - Occurrence of secretogranin II in the prolactin-immunoreactive neurons of the rat
      lateral hypothalamus: an in situ hybridization and immunocytochemical study.
AB  - The occurrence of secretogranin II in a neuron population of the rat lateral
      hypothalamus specifically detected by an anti-serum to ovine prolactin was
      examined. As this population was previously reported to synthesize dynorphin, the
      distribution of neurons recognized by ovine prolactin-, dynorphin B- and
      secretogranin II anti-sera was investigated on adjacent sections of hypothalami.
      The prolactin immunoreactive neurons were the only cells in the lateral
      hypothalamus to be stained by secretogranin II anti-serum. Moreover, coupling
      immunocytochemical detection and in situ hybridization with an oligonucleotide
      probe complementary to secretogranin II mRNA showed that these neurons expressed
      the secretogranin II gene. These new findings should help to study the
      physiological role of the prolactin immunoreactive neurons of the lateral
      hypothalamus.

PMID- 8561950
TI  - Autoradiographic localization of D1-like dopamine receptors in the forebrain of
      male and female Japanese quail and their relationship with immunoreactive
      tyrosine hydroxylase.
AB  - The distribution of D1-like dopamine receptors was studied in the brain of male
      and female Japanese quail (Coturnix japonica) by means of quantitative
      autoradiography with 3H-labelled D1 selective antagonist, SCH 23390, serving as a
      ligand. A specific, saturable, high affinity binding of this ligand was
      demonstrated. High densities of binding sites were detected in the lobus
      parolfactorius, olfactory tubercle, and paleostriatum augmentatum. Medium
      densities were observed in the entire neostriatum and in the external layers of
      the optic tectum. Similar levels of binding outlined the paleostriatum
      primitivum, the nucleus pretecalis and the nucleus intercollicularis. Low but
      significant levels of receptors were also present in the medial preoptic area at
      the level of the sexually dimorphic medial preoptic nucleus and throughout the
      infundibulum, as well as in the ectostriatum, medial and lateral septum, and
      nucleus accumbens. At the level of the medial septum, just dorsal to the anterior
      commissure, two circular areas of high receptor density corresponding to the
      nucleus of the septal commissure were also observed. No sex difference in
      receptor density could be detected in any of the areas. All areas containing high
      densities of D1 receptors also contained high densities of tyrosine hydroxylase
      (TH) fibers. However, certain areas characterized by a high density of TH
      immunoreactive fibers did not contain appreciable densities of D1-like dopamine
      receptors. The distribution of this receptor and its relationship to TH
      immunoreactivity is consistent with observations made in other vertebrates,
      suggesting that the dopaminergic system is evolutionarily highly conserved among
      amniote vertebrates.

PMID- 8561951
TI  - Distribution of parvalbumin-containing interneurons in the hippocampus of the
      gerbil--a qualitative and quantitative statistical analysis.
AB  - In the gerbil (Meriones unguiculatus) hippocampal formation, the calcium-binding
      protein parvalbumin (PV) shows a unique species-specific distribution: it is
      present in the perforant path from the entorhinal cortex to the stratum molecular
      of the dentate are and cornu ammonis. A possible relation of this to the seizure
      sensitivity of gerbils has been suggested. In addition, as in other species, PV
      is contained in a subpopulation of GABAergic nerve cells of the gerbil
      hippocampus. The characteristics of these PV-containing neurons are here
      described. Distribution and shape of the PV-positive neurons in general agreed
      with the features described for rat hippocampus with two notable exceptions: in
      CA2 PV-containing perikarya were densely crowded and gave rise to an intense
      immunoreactive plexus around the pyramidal cells and, in CA1, the number of
      stained neurons was variable, often much lower than in rats and occasionally not
      a single PV-positive neuron was present. In parasagittal brain sections of the
      lateralities 1.0, 1.6 and 2.2 mm from the midline, obtained from 27 male gerbils,
      the number of PV-containing neurons was determined. The data set obtained in CA3
      and dentate area resembled unimodal distributions, while in CA1 a bimodal
      frequency distribution was present. Since parametric and non-parametric
      correlation tests rely on a unimodal distribution of the data set, they gave
      falsely significant values in CA1. The bimodal distribution suggests that, with
      respect to the PV-containing interneurons in CA1, two different populations of
      gerbils were included in our sample, those with many positive neurons and those
      with only a few. Since the nerve terminal staining is preserved also in those
      gerbils with only a few positive perikarya in CA1, it seems possible that an
      unknown factor influenced PV expression and storage in the soma. Sex, age,
      seasonal or circadian rhythm or quality of immunocytochemical staining did not
      influence the outcome of the quantitative analysis. However, a relation of the
      expression of the high affinity calcium buffering PV in interneurons and the
      individual seizure sensitivity of the gerbil is considered.

PMID- 8561952
TI  - Localization of enkephalinergic neurons in the central nervous system of the
      salmon (Salmo salar L.) by in situ hybridization and immunocytochemistry.
AB  - The distribution of neurons expressing preproenkephalin (PPE) mRNA in the brain
      of the salmon was investigated by means of non-radioactive in situ hybridization,
      and directly compared with the distribution of enkephalin-immunoreactive (ENKir)
      neurons. This approach, utilized here for the first time in a non-mammalian
      vertebrate for the identification of neurons containing opioid peptides,
      permitted a detailed analysis of the distribution of putative enkephalinergic
      neurons in the salmon brain. Several cell groups containing neurons that express
      PPE mRNA also contain ENKir neurons. Such cell groups are located in the ventral
      telencephalic area, the nucleus of the rostral mesencephalic tegmentum and
      another nucleus immediately dorsal to it, the torus semicircularis, the valvula
      cerebelli and the corpus cerebelli. These cell groups consistently contain larger
      numbers of PPE mRNA expressing cells than ENKir ones. Some cell groups express
      PPE mRNA, but do not contain ENKir neurons. These cell groups are located in the
      dorsal telencephalic area, the inferior lobes of the hypothalamus, the pretectal
      area, the magnocellular superficial pretectal nucleus, the optic tectum, the
      oculomotor nucleus, the trochlear nucleus, the magnocellular vestibular nucleus,
      the secondary gustatory nucleus, the superior and medial reticular nuclei, the
      motor nucleus of the vagus and the ventral horn of the spinal cord. Moreover,
      some cell groups contain ENKir neurons, but no PPE mRNA expressing neurons. These
      cell groups are located in the ventromedial thalamic nucleus, the lateral tuberal
      nucleus, the nucleus of the lateral recess and the nucleus of the posterior
      recess. The majority of these periventricular ENKir neurons were of the
      cerebrospinal fluid-contacting type. ENKir neurons were also located in the
      dorsal lateral tegmental nucleus and in area B9. The results also permitted a
      tentative identification of enkephalinergic neurons afferent to the optic tectum,
      that have previously not been identified with immunocytochemistry, located in the
      dorsal telencephalic area, as well as enkephalinergic neurons intrinsic to the
      tectum that may contribute to the laminar arrangement of ENKir fibers in the
      optic tectum.

PMID- 8561953
TI  - Comparative laminar distribution of various autoradiographic cholinergic markers
      in adult rat main olfactory bulb.
AB  - To provide anatomical information on the complex effects of acetylcholine (ACh)
      in the olfactory bulb (OB), the distribution of different cholinergic muscarinic
      and nicotinic receptor sub-types was studied by quantitative in vitro
      autoradiography. The muscarinic M1-like and M2-like sub-types, as well as the
      nicotinic bungarotoxin-insensitive (alpha 4 beta 2-like) and bungarotoxin
      sensitive (alpha 7-like) receptors were visualized using [3H]pirenzepine, [3H]AF
      DX 384, [3H]cytisine and [125I] alpha-bungarotoxin (BTX), respectively. In
      parallel, labelling patterns of [3H]vesamicol (vesicular acetylcholine transport
      sites) and [3H]hemicholinium-3 (high-affinity choline uptake sites), two putative
      markers of cholinergic nerve terminals, were investigated. Specific labelling for
      each cholinergic radioligand is distributed according to a characteristic laminar
      and regional pattern within the OB revealing the lack of a clear overlap between
      cholinergic afferents and receptors. The presynaptic markers, [3H]vesamicol and
      [3H]hemicholinium-3, demonstrated similar laminar pattern of distribution with
      two strongly labelled bands corresponding to the glomerular layer and the area
      around the mitral cell layer. Muscarinic M1-like and M2-like receptor sub-types
      exhibited unique distribution with their highest levels seen in the external
      plexiform layer (EPL). Intermediate M1-like and M2-like binding densities were
      found throughout the deeper bulbar layers. In the glomerular layer, the levels of
      muscarinic receptor subtypes were low, the level of M2-like sites being higher
      than M1. Both types of nicotinic receptor sub-types displayed distinct
      distribution pattern. Whereas [125I] alpha-BTX binding sites were mostly
      concentrated in the superficial bulbar layers, [3H]cytisine binding was found in
      the glomerular layers, as well as the mitral cell layer and the underlying
      laminae. An interesting feature of the present study is the visualization of two
      distinct cholinoceptive glomerular subsets in the posterior OB. The first one
      exhibited high levels of both [3H]vesamicol and [3H]hemicholinium-3 sites. It
      corresponds to the previously identified atypical glomeruli and apparently failed
      to express any of the cholinergic receptors under study. In contrast, the second
      subset of glomeruli is not enriched with cholinergic nerve terminal markers but
      displayed high amounts of [3H]cytisine/nicotinic binding sites. Taken together,
      these results suggest that although muscarinic receptors have been hypothesized
      to be mostly involved in cholinergic olfactory processing and short-term memory
      in the OB, nicotinic receptors, especially of the cytisine/ alpha 4 beta 2 sub
      type, may have important roles in mediating olfactory transmission of efferent
      neurons as well as in a subset of olfactory glomeruli.

PMID- 8561955
TI  - Cellular and Molecular Mechanisms of Drugs of Abuse: Cocaine and Methamphetamine.
      Symposium proceedings. Nice, France, August 19-20, 1993.

PMID- 8561954
TI  - A review of the effects of dopaminergic agents on humans, animals, and drug
      seeking behavior, and its implications for medication development. Focus on GBR
      12909.
AB  - Medication development for cocaine abuse has focused on potential mechanisms of
      action related to the abuse of cocaine. The hypothesis that mesolimbic dopamine
      (DA) is the key neurochemical mediator of cocaine's addictive and reinforcing
      effects is well supported by a wide variety of data from animal studies. On the
      other hand, medications that increase DA or block its action in humans can
      produce effects that appear incompatible with this hypothesis. This article
      reviews these incompatibilities between animal and human data with a focus on the
      DAergic actions of drugs, including DA reuptake inhibitors, direct DA agonists,
      DA increasers, and DA antagonists. Possible reasons for these discrepancies are
      discussed, and the potential role of high-affinity DA uptake inhibitors, such as
      GBR12909, for pharmacotherapies for treating cocaine addiction in humans is
      likely to come from understanding its mechanisms of action, it is clear that
      further research on the effects of cocaine in humans and animals will be critical
      to the medication development effort.

PMID- 8561956
TI  - Rat mesencephalic neuronal cells cultured for different periods as a model of
      dopamine transporter ontogenesis.
AB  - Ventral mesencephalic neurons contained only low-affinity and sodium-independent
      binding sites of [3H]WIN 35,428 (marker of dopamine transporter) during the first
      10 d in primary cultures. These sites were present in cytosol, and they are not
      very probably related to dopamine transporter. After 12 d in culture, membrane
      bound, high-affinity, and sodium-dependent [3H]WIN 35,428 binding sites were
      detected. In membranes prepared from cells 14 d in culture, cocaine displaced
      [3H]WIN 35,428 binding with similar potency to that in striatal membranes of
      adult rat brain. The high-affinity [3H]WIN 35,428 binding sites in mesencephalic
      neuronal cell cultures are very probably related to dopamine transporter. The
      development of high-affinity [3H]WIN 35,428 binding sites in neurons cultured for
      different time periods could be a useful model of dopamine transporter
      ontogenesis.

PMID- 8561957
TI  - Interactive effects of prenatal cocaine and nicotine exposure on maternal
      toxicity, postnatal development and behavior in the rat.
AB  - Two experiments were performed to investigate the interactive effects of prenatal
      coadministration of cocaine hydrochloride (C) and nicotine tartrate (N).
      Experiment I was designed to determine doses of C and N that could be
      coadministered without altering maternal gestational parameters and/or fetal
      viability. Exposure of Sprague-Dawley rats to combined high-dose C (20 mg/kg) and
      high-dose N (5.0 mg/kg) on gestation days 8-21 was not more toxic to dam or fetus
      that that of exposure to C alone. Experiment II investigated pregnancy outcome,
      postnatal development, and behavior of the offspring following drug exposure to
      either high-dose cocaine (20 mg/kg: CS), high-dose nicotine (5.0 mg/kg: NS), or
      both (NC) on gestation days 8-21. N was administered by osmotic minipump and C by
      sc injection. Saline-injected dams, fitted with saline-fitted pumps (SS), and
      untreated dams, pair-fed (PF) to NC females, served as controls. Alterations in
      maternal variables were limited to a 10-15% decrease in food consumption in NC
      and CS groups. Pregnancy outcome and birth statistics were unaffected by prenatal
      treatment, as was offspring body weight during the first four postnatal weeks.
      However, the development of surface righting was delayed inC CS pups, and only CS
      offspring were underresponsive to the stimulatory effects of dopamine agonists on
      activity and stereotypy. Behavioral responses to N challenge were similar in all
      groups. In addition, only CS offspring showed altered behavioral responses in a
      spontaneous alternation task. Treatment effects on dopamine D1 and D2 binding in
      the caudate nucleus were not observed. The combination of N and C did not
      exacerbate any of the behavioral changes seen in CS offspring. These results
      support the hypothesis that C is a behavioral teratogen in rodents, and suggest
      that in the present model, nicotine can mitigate some of the consequences of in
      utero exposure to cocaine.

PMID- 8561958
TI  - Drug-induced circling preference in rats. Correlation with monoamine levels.
AB  - Drugs of abuse, such as phencyclidine (PCP), methamphetamine (METH), and cocaine
      (COC) are known to affect several behaviors in rats, such as motor activity,
      stereotypy, and circling. In this study, we evaluated whether these drugs produce
      circling preferences in the presence or absence of unilateral 6-hydroxydopamine
      (6-OHDA)-induced lesions of the caudate nucleus. Adult male CD rats were lesioned
      with 10 micrograms 6-OHDA/site. Animals were dosed with PCP (15 mg/kg, ip) its
      congener (+) MK-801 (0.15 mg/kp, ip), METH (2 mg/kg, ip) COC (60 mg/kp, ip), or
      apomorphine (0.2 mg/kg, ip). Circling preference was recorded in control and
      lesioned rats for 2 h before animals were sacrificed to determined monoamine
      levels by HPLC/EC. In control animals, administration of these drugs produced 60
      70% left circling. In lesioned animals, these drugs produced 78-90% ipsilateral
      (toward the lesion) circling, except apomorphine, which produced 60-80%
      contralateral (away from the lesion) circling. Dopamine (DA) and its metabolites
      3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations
      significantly decreased ipsilaterally in lesioned caudate nucleus (CN) and
      substantia nigra (SN). However, no significant changes were observed in nucleus
      accumbens (NA) and olfactory tubercles (OT). These data demonstrate that drugs of
      abuse like PCP, its congener (+) MK-801, METH, and COC produce a greater
      preference to turn toward the left than the right, a finding similar to that
      found in human psychosis. Since 6-OHDA lesions enhanced the circling bias and
      depleted DA and its metabolites DOPAC and HVA, it also suggests that the
      dopaminergic system may be involved in the circling behavior.

PMID- 8561959
TI  - Neurotoxicity, drugs and abuse, and the CuZn-superoxide dismutase transgenic
      mice.
AB  - Administration of methamphetamine (METH) to animals causes loss of DA terminals
      in the brain. The manner by which METH causes these changes in neurotoxicity is
      not known. We have tested the effects of this drug in copper/zinc (CuZn)
      superoxide dismutase transgenic (SOD Tg) mice, which express the human CuZnSOD
      gene. In nontransgenic (non-Tg) mice, acute METH administration causes
      significant decreases in DA and dihydroxyphenylacetic acid (DOPAC) in the striata
      of non-Tg mice. In contrast, there were on significant decreases in striatal DA
      in the METH administration caused decreases in striatal DA and DOPAC in the non
      Tg mice, but not in the SOD-Tg mice. Similar studies were carried out with 1
      methyl-1,2,3,6-tetrahydropyridine (MPTP), which also causes striatal DA and DOPAC
      depletion. As in the case of METH, MPTP causes marked depletion of DA and DOPAC
      in the non-Tg mice, but not in the SOD Tg mice. These results suggest that the
      mechanisms of toxicity of both METH and MPTP involved superoxide radical
      formation.

PMID- 8561960
TI  - The nature of d,l-fenfluramine-induced 5-HT reuptake transporter loss in rats.
AB  - The administration of the anorexigenic drug d,l-fenfluramine (Ponderax) to
      laboratory animals results in a dose-dependent reduction in presynaptically
      located serotonergic reuptake transporter protein. This long-term effect may
      represent an altered mechanism of synthesis of the transporter (downregulation).
      Alternatively, fenfluramine may destroy the serotonergic terminals on which 5-HT
      transporters are located. To distinguish between these two alternatives, we
      applied an assay of neurotransmitter-specific nerve endings (alpha) to brain
      tissue from two animal models of reduced 5-HT transporter density. In Model 1,
      serotonergic nerve terminals were destroyed (rats received 5,7
      dihydroxytryptamine [5,7-DHT] intracisternally); in Model 2, there was a loss of
      5-HT transporter per se on otherwise intact serotonergic nerve terminals. The
      manner in which alpha declined as transporter density was decreased (reducing
      Vmax values) in animal Models 1 and 2 was found to be significantly different. In
      rats treated with fenfluramine, the association between 5-HT transporter density
      and alpha was the same as in the neurotoxic model.

PMID- 8561961
TI  - The role of temperature, stress, and other factors in the neurotoxicity of the
      substituted amphetamines 3,4-methylenedioxymethamphetamine and fenfluramine.
AB  - Amphetamines (AMPs) can cause long-term depletions in striatal dopamine (DA) and
      serotonin (5-HT), and these decrements are often accepted as prima facie evidence
      of AMP-induced damage to the dopaminergic and serotonergic projections to
      striatum. Rarely are indices linked to neural damage used to evaluate the
      neurotoxicity of the AMPs. Here, we determined the potential neurotoxic effects
      of two substituted AMPs, d-methylenedioxymethamphetamine (d-MDMA) and d
      fenfluramine (d-FEN) in group-housed female C57BL6/J mice. Astrogliosis, assessed
      by quantification of glial fibrillary acidic protein (GFAP), was the main
      indicator of d-MDMA-induced neural damage. Assays of tyrosine hydroxylase (TH),
      DA, and 5-HT were used to determine effects on DA and 5-HT systems. Since AMPs
      are noted for both their stimulatory and hyperthermia-inducing properties,
      activity, as well as core temperature, was monitored in several experiments. To
      extend the generality of our findings, these same end points were examined in
      singly housed female C57bL6/J mice and in group-housed male C57BL6/J or female
      B6C3F1 mice after treatment with d-MDMA. Mice received either d-MDMA (20 mg/kg)
      (singly housed mice received dosages of 20, 30, or 40 mg/kg) or d-FEN (25 mg/kg)
      every 2 h for a total of four sc injections. d-MDMA caused hyperthermia, whereas
      d-FEN induced hypothermia. d-MDMA cause a large (300%) increase in striatal GFAP
      that resolved by 3 wk and a 50-75% decrease in TH and DA that was still apparent
      at 3 wk, d-FEN did not affect any parameters in striatum. d-MDMA is a striatal
      dopaminergic neurotoxicant in both male and female C57BL6/mice, as evidenced by
      astrogliosis and depletions of DA in this area in both sexes. The greater
      lethality to males suggests they may be more sensitive, at least to the general
      toxicity of d-MDMA, that females. d-MDMA (20 mg/kg) induced the same degree of
      damage whether mice were housed singly or in groups. Higher dosages in singly
      housed mice induced greater lethality, but not greater neurotoxicity. d-MDMA was
      also effective in inducing striatal damage in mice of the B6C3F1 strain.
      Significant increases in activity were induced by d-MDMA, and these increases
      were not blocked by pretreatment with MK-801, despite the profound lowering of
      body temperature induced by this combination. A lowering of body temperature,
      whether by a 15 degree C ambient temperature (approx 2 degree drop), pretreatment
      with MK-801 (1.0 mg/kg prior to the first and third d-MDMA injections; approx 5-6
      degrees C drop) or restraint (approx 5-6 degrees C drop) was effective in
      blocking the neurotoxicity of d-MDMA in both C57BL6/J and B6C3F1. The stimulatory
      effects of d-MDMA appeared to have little impact on the neurotoxicity induced by
      d-MDMA or the protection conferred by MK-801. These data suggest that in the
      mouse, the neurotoxic effects of d-MDMA, and most likly other AMPs, are linked to
      an effect on body temperature.

PMID- 8561962
TI  - The use of toxicokinetics for the safety assessment of drugs acting in the brain.
AB  - Pharmacological and toxicological studies undertaken on drugs that affect the
      brain are frequently performed in disparate species under various experimental
      conditions, at doses often greatly in excess of those expected to be administered
      to humans, and the findings are extrapolated implicitly or explicitly with scant
      regard to differences in the biodisposition of the drugs. Such considerations are
      necessary since: 1. Species; 2. Strain; 3. Gender; 4. Route; 5. Dose; 6.
      Frequency and time of administration; 7. Temperature; 8. Coadministration of
      drugs; and 9. Surgical manipulation are but some of the factors that have been
      shown to influence the kinetics and metabolism of drugs. This article, using MDMA
      and other phenylethylamines as examples, provides evidence for the need to
      measure the exposure of the drugs and their active metabolites in blood and brain
      (toxicokinetics) in order that conclusions based only on dynamic, biochemical, or
      histological evidence are more pertinent. Further, the combined use of
      toxicokinetic-dynamic modeling can lead to a better appreciation of the
      mechanisms involved and a more useful approach to the calculation of safety
      margins.

PMID- 8561963
TI  - Catecholamine and MHPG plasma levels, platelet MAO activity, and 3H-imipramine
      binding in heroin and cocaine addicts.
AB  - This work evaluated in a population of heroin and heroin plus cocaine human
      addicts: 1. Norepinephrine (NE), epinephrine (Epi) and 3-methoxy-4
      hydroxyphenylglycol (MHPG) (the principal metabolite of brain NE) plasma levels;
      2. Monoamine oxidase (MAO) activity; and 3. 3H-imipramine specific binding to the
      amine carrier in platelets. NE plasma levels were significantly lower in the
      short-term heroin user groups (1-3 and 4-6 yr), a finding not observed in both
      long-term heroin user ( > 6 yr) and heroin plus cocaine user ( > 6 yr) groups.
      Epi levels changed in a similar manner, except that a significant increase was
      noted in heroin plus cocaine abusers. Conversely, dopamine and MHPG plasma levels
      increased with the duration of heroin use, and even more with cocaine abuse.
      Platelet MAO activity increased in all groups. Specific 3H-imipramine binding
      sites showed an increase after 3 yr of heroin abuse and in all heroin plus
      cocaine addicts. In conclusion, short-term use of heroin decreases NE or Epi
      release, but with prolonged use, a slow adaptation occurs. In contrast, cocaine
      inhibits the neuronal Epi uptake, even in a situation of long duration of abuse.
      Probably the amine levels additionally regulate the amine carrier, resulting in
      changes that show a different pattern from major depression. These drugs of abuse
      may also influence directly or indirectly related enzymatic systems.

PMID- 8561964
TI  - Cocaine kindling in mice. Responses to N-methyl-D,L-aspartate (NMDLA) and L
      arginine.
AB  - Previous studies proposed the involvement of the N-methyl-D-aspartate (NMDA) type
      of glutamate receptors in the development of sensitization to the convulsive
      effect of cocaine (cocaine kindling). The present study was undertaken to
      determine, first, if cocaine kindling is associated with enhanced sensitivity of
      the NMDA receptor to the convulsive response of N-methyl-D,L-aspartate (NMDLA),
      and second, whether in vivo modulation of nitric oxide synthase (NOS) function
      regulates the development of cocaine kindling. The following results were
      observed: 1. Cocaine-kindled animals were significantly more susceptible to the
      convulsive effect of the NMDA receptor agonist NMDLA than saline controls; 2.
      Pretreatment with the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 100
      mg/kg; ip) blocked the development of cocaine kindling; 3. The protective effect
      of L-NAME was partially reversed with the coadministration of the NOS substrate,
      L-arginine (300 mg/kg; ip), but not D-arginine; and 4. L-Arginine (300 mg/kg;
      ip), but not D-arginine, amplified the development of cocaine kindling. Taken
      together, these findings suggest that supersensitivity of the NMDA receptor and
      activation of NOS may underlie the development of cocaine kindling.

PMID- 8561965
TI  - The effect on methamphetamine on the mRNA level for 14.3.3 eta chain in the human
      cultured cells.
AB  - 14.3.3 protein, a brain-specific protein, is an activator of tyrosine and
      tryptophan hydroxylases, key enzymes for biosynthesis of dopamine and serotonin.
      In this article, we describe cloning of cDNA for human brain 14.3.3 eta chain and
      expression of 14.3.3 eta chain mRNA in some human cultured cells. The cloned cDNA
      is 1730 bp long and contains 191 bp of a 5'-noncoding region, the complete 738 bp
      of coding region, and 801 bp of a 3'-noncoding region, containing three
      polyadenylation signals. This cDNA encoded a polypeptide of 246 amino acids (M(r)
      28,196). Furthermore, using in situ hybridization histochemistry, the expression
      of mRNA for this protein was examined in the rat central nervous system. In situ
      hybridization histochemistry indicated that 14.3.3 eta chain mRNA is detected not
      only in the monoamine-synthetic neurons, but also in other neurons in the
      discrete nuclei, which synthesize neither cathecholamine nor serotonin. Northern
      blot analysis demonstrated that the addition of methamphetamine into the cultured
      medium increased the mRNA level for 14.3.3 eta chain in U-251 cells, but did not
      increase that of GFAP.

PMID- 8561966
TI  - Behavioral sensitization and tolerance to cocaine and the occupation of dopamine
      receptors by dopamine.
AB  - Data from the authors' laboratory on the neural substrates of Pavlovian
      conditioning and behavioral sensitization to psychomotor stimulants are reviewed.
      The findings of a recent experiment on the role of occupation of dopamine
      receptors by dopamine and its association to behavioral sensitization are
      reported. Daily intermittent injections of cocaine produced behavioral
      sensitization to the locomotor response in rats, whereas continuous cocaine
      infusions produced behavioral tolerance. Behavioral sensitization to cocaine was
      blocked by coadministration of nimodipine, an L-type calcium channel blocker. The
      increase in locomotion produced by cocaine was associated with an increase in the
      occupation of striatal dopamine D1 and D2 receptors, measured as the density of
      receptors protected from denaturation by N-ethoxycarbonyl-2-ethoxy-1, 2
      dihydroquinoline (EEDQ). This association was not observed when rats were given a
      challenge injection of cocaine 10 d after withdrawal from similar treatment
      regimens. Rats given a cocaine challenge after withdrawal from either
      intermittent or continuous cocaine treatments regimens exhibited increased
      occupation of striatal D1 and D2 receptors. This increase was similar in
      magnitude to that observed in rats without a history of cocaine treatments after
      a challenge injection of cocaine. This suggests that the differences in occupancy
      of striatal dopamine receptors by dopamine observed in the prewithdrawal
      condition are likely the results of differences in brain levels of cocaine
      achieved by the two treatment regimens. Occupancy of striatal dopamine D1 and D2
      receptors does not appear to be related to the development of sensitization to
      the motor-stimulating effects of cocaine.

PMID- 8561967
TI  - Cocaine. Selective regional effects on central monoamines.
AB  - Cocaine HCl (0, 10, or 50 mg/kg) was injected into adult male ICR mice ip. Thirty
      minutes later, the brains were removed, and nine regions were isolated: olfactory
      bulbs, olfactory tubercles, prefrontal cortex, septum, striatum, amygdala,
      hypothalamus, hippocampus, and thalamus. Using high-performance liquid
      chromatography, concentrations of norepinephrine, dopamine, serotonin, and their
      major metabolites and the metabolite/neurotransmitter ratios were determined as
      an indicator of utilization. Serotonergic systems responded most dramatically.
      5HIAA/5-HT decreases were seen in all the brain regions, except the septum,
      hippocampus, and olfactory bulbs. In most instances, the alterations were dose
      dependent. The most profound changes were seen in the amygdala, prefrontal
      cortex, hypothalamus, and thalamus. For noradrenergic systems, significant
      responses were seen only in the amygdala, prefrontal cortex, and hypothalamus,
      but then only at the lower dose. The dopaminergic responses were more complex and
      not always dose-dependent. The DOPAC/DA ratio was decreased only in the amygdala
      and striatum at the lower dose, and the olfactory tubercles at the higher dose.
      It was increased in the septum. The HVA/DA ratios were decreased in the amygdala,
      prefrontal cortex, and hypothalamus, but only at the lower dose (like MHPG/NE).
      The 3MT/DA ratio was decreased in the thalamus at the lower dose and in the
      olfactory tubercles at the higher dose, whereas it was increased in the
      prefrontal cortex at the lower dose. The HVA and DOPAC routes of degradation were
      both utilized only by the amygdala. Thus, cocaine produced its most comprehensive
      effects in this nucleus, as well as the greatest absolute percentage changes for
      all three of the monoamine systems studied.

PMID- 8561968
TI  - Behavioral and neurochemical changes in the dopaminergic system after repeated
      cocaine administration.
AB  - In order to determine whether repeated cocaine administration produced persistent
      changes in dopamine (DA) receptor binding and release consistent with behavioral
      sensitization, rats were treated with either cocaine (25 mg/kg ip) or saline
      twice daily for 14 consecutive days followed by a 3-d withdrawal period. The DA
      transporter site was assayed using [3H]GBR 12935, whereas D1 and D2 sites were
      assayed using [3H]SCH 23390 and [3H]spiperone, respectively. The density (Bmax)
      of the DA transporter binding sites in the ST of the cocaine-treated group
      increased significantly (p < 0.05) over controls 3 d after the last injection,
      whereas the density of striatal D1 and D2 binding sites remained unchanged. The
      DA transporter in the nucleus accumbens (NA) was also studied with [3H]GBR 12935
      and was unchanged following drug treatment. D1 and D2 binding parameters for the
      NA were not determined in this study. Furthermore, cocaine administration did not
      affect the affinities (Kd) of the radioligands used to label the transporter, D1,
      or D2 sites in any of the studies performed. In addition, striatal DA release was
      measured using in vivo microdialysis in anesthetized rats. Linear regression
      analysis on maximal decreases in DA release after apomorphine (0.02, 0.2, and 2.0
      mg/kg sc) injection showed no difference in the functional capacity of the ST to
      modulate DA transmission between control and treated groups. Moreover, animals
      pretreated with cocaine showed a significant (p < 0.01) decrease in locomotor
      activity (LA) after a presynaptic, autoregulating dose of apomorphine (0.03 mg/kg
      sc) was given. These results suggests that the effects seen after repeated
      exposure to cocaine may be regulated, in part, by changes in striatal DA
      transporter binding site densities and not necessarily by DA-releasing mechanisms
      or D1 and D2 receptor modification.

PMID- 8561969
TI  - Prenatal cocaine exposure revealed minimal postnatal changes in rat striatal
      dopamine D2 receptor sites and mRNA levels in the offspring.
AB  - It has been reported from this laboratory that prenatal cocaine exposure results
      in the postnatal transient alterations of rat striatal dopamine uptake sites
      examined from postnatal 0-32 wk. The present study aims to examine whether this
      will result in a direct/indirect stimulation of dopamine D2 receptors. Pregnant
      rats were dosed orally with cocaine hydrochloride (60 mg/kg/d) from gestational
      day (GD) 7-21. Control animals received an equivalent volume of water. The
      striatum from the offspring at postnatal 0-32 wk was examined. The radioligand
      [3H]sulpiride was used for the Scatchard analysis of the D2 receptors, and the
      changes in the levels of mRNA for the D2 receptor were studied using Northern
      blot analysis. Results from the present study revealed that in the control group,
      there was an age-dependent increase in the number of D2 receptor sites (Bmax:
      44.00 +/- 2.12 to 178.00 +/- 45.10 fmol/mg protein) and in the levels of D2 mRNA
      from PN0-32 wk with the most rapid increase occurring during the first 4 wk of
      postnatal development. Prenatal cocaine exposure resulting in only a significant
      decrease (p < 0.001) in the number of D2 receptor sites at PN0 wk and in a 10%
      increase in mRNA levels at PN3, 4, and 12 wk. It was concluded from this study
      that prenatal cocaine exposure resulted in minimal postnatal changes in the
      dopamine D2 receptor.

PMID- 8561970
TI  - Effects of prenatal cocaine exposure in the photoreceptor cells of the rat
      retina.
AB  - Despite the increasing evidence of eye abnormalities, the effects of prenatal
      exposure to cocaine on the visual system are still poorly understood. This study
      was aimed at analyzing the qualitative and quantitative organization of the
      retinal photoreceptor cells (PR) and outer nuclear layer (ONL) after prenatal
      exposure to cocaine in the rat. Pregnant Wistar rats were given sc injections of
      cocaine hydrochloride (60 mg/kg body wt/d) or saline or were not manipulated;
      analyses were performed in the 14- and 30-d-old male offspring. Radial semithin
      and ultrathin sections of epon-embedded flat mounts of the retina showed
      displaced PR-like cells in the inner nuclear layer (INL), picnotic PR nuclei in
      INL, and ONL, and retinal PR rosettes and outer-segment debris in the subretinal
      space. The quantitative study showed an increased density of PR-like nuclei in
      the INL in PND14 cocaine-treated rats that were within normal values at PND30; no
      changes were detected in the PR mean nuclear diameter and in the packing density
      of PR nuclei in the ONL. These data constitute the first morphological
      demonstration of photoreceptor damage after prenatal cocaine-exposure probably
      owing to a direct action of the drug and/or to the cocaine-induced
      ischemia/hypoxia.

PMID- 8561973
TI  - Do asymptomatic HIV-seropositive individuals show cognitive deficit?

PMID- 8561971
TI  - Effects of prenatal cocaine exposure in the retinal ganglion cell layer of the
      rat. A morphometric analysis.
AB  - To study the effects of prenatal cocaine-exposure on the developing retinal
      ganglion cell layer of the rat, female Wistar rats were administered
      subcutaneously (sc) cocaine hydrochloride (60 mg/kg body wt/d) or saline, or were
      not manipulated from gestational d 8-22. Male offspring were sacrificed at
      postnatal day 14 and 30. Radial semithin sections of epon-embedded flat mounts of
      the retinal quadrants were used to evaluate the following parameters along the
      centroperipheral axis: 1. Thickness of ganglion cells plus nerve fiber layer; 2.
      Nuclear size of ganglion cell layer neurons; and 3. Linear density (number per
      unit length) of ganglion cell layer neurons. To study the effects of cocaine and
      age on the retinal areas (temporal/nasal, dorsal/ventral), a repeated measures
      analysis of variance was used for each of the parameters mentioned above. All
      parameters were affected by prenatal exposure to cocaine. The thickness of the
      ganglion cell plus nerve fiber layer was reduced in cocaine-exposed rats in
      comparison with the saline group. Nuclear diameters were smaller in the cocaine
      than in the saline and control groups. The linear density was higher in the
      cocaine-exposed group than in the control and saline groups. The age-dependent
      decrease in the linear density from postnatal day 14-30 was higher in the cocaine
      exposed rats than in the saline group; the decrease in the linear density along
      the centroperipheral axis found in both the control and saline groups was not
      significant in the cocaine-treated group. These morphometric findings strongly
      support the view that prenatal cocaine-exposure induces marked changes in the
      organization of the developing retina.

PMID- 8561972
TI  - Effects of prenatal cocaine exposure in the prefrontal cortex of the rat. A
      morphometric evaluation.
AB  - This work was undertaken in order to assess the organization of the prelimbic
      area of the medial prefrontal cortex of rats exposed prenatally to cocaine.
      Pregnant Wistar rats were assigned to the following groups: 1. Cocaine--60 mg/kg
      body wt/d sc, from gestational days 8-22; 2. Saline; 3. Pair-fed; and 4.
      Nonmanipulated. Male offspring were perfused on postnatal days 14 and 30. Six
      brains per group and per age were embedded in celloidin to calculate the volumes
      of the prelimbic area; sections from the other six brains were embedded in resin
      and processed for electron microscopy. Using semithin sections (2 microns) of
      layers II-III and V-VI, the following parameters were calculated: 1. The fraction
      of the neuropil occupied by neurons (VV); 2. The packing (NA) density; and 3. The
      numerical (NV) density. Qualitative alterations consisted of dispersed profiles
      of degenerated neurons and dendrites in the medial prefrontal cortex. No
      significant differences were found in the gross morphometric parameters when the
      cocaine group was compared with the other groups. A high interanimal variation
      was shown in the prelimbic volumes of postnatal day (PND) 14 cocaine-treated
      rats, and a a decrease in volumes was detected at PND30. Although there are some
      alterations in the main afferent cortical target area for dopaminergic input, its
      gross morphometric parameters do not seem to be sufficiently affected to account
      for the behavioral alterations referred to as being dependent on this brain
      region.

PMID- 8561974
TI  - Autocrine interferon-beta synthesis for gene therapy of HIV infection: increased
      resistance to HIV-1 in lymphocytes from healthy and HIV-infected individuals.
AB  - OBJECTIVE: To explore the possibility of gene therapy of HIV infection based on
      the multiple antiretroviral activities of interferon (IFN)-beta. DESIGN: We
      introduced into HIV target cells an IFN-beta gene placed under an expression
      control ensuring a low and constitutive expression, sufficient to confer a
      permanent antiviral state without impeding normal cell function. METHODS: We
      transformed, with an efficacy ranging from 20-55%, peripheral blood lymphocytes
      (PBL) derived from healthy, seronegative donors, and from asymptomatic HIV
      infected individuals by the HMB-KbHuIFN beta retroviral vector carrying the human
      IFN-beta coding sequence driven by a fragment of the murine H-2Kb gene promoter.
      RESULTS: The replication rate of the IFN-beta-expressing cells was no different
      from that of untransformed controls during the 21-day period of in vitro
      observation. When IFN-beta-transformed, purified CD4+ lymphocytes from healthy
      donors were HIV-1LAI-infected, virus replication was inhibited and most of the
      cells survived, in contrast to untransformed CD4+ cells which were all destroyed
      12 days after infection. Protection of CD4+ cells from the same donors was also
      observed in suspensions of IFN-beta-transformed total PBL that were infected with
      HIV-1LAI. In IFN-beta-transformed PBL from four HIV-infected donors, endogenous
      HIV replication was decreased and 28-69% of the CD4+ cells survived at the end of
      the 21 days in culture. In the untransformed control PBL suspensions, all CD4+
      cells were destroyed. In long-term experiments, HIV-infected, IFN-beta
      transformed cell populations of the lymphocytic CEM and the promonocytic U937
      line were kept in culture for 60 days, during which time they remained resistant
      to HIV infection. CONCLUSION: These results indicate that further exploration of
      autocrine IFN-beta production for somatic cell gene therapy of HIV infection is
      warranted.

PMID- 8561975
TI  - The gp120 envelope of HIV-1 binds peptides in a similar manner to human leukocyte
      antigens.
AB  - OBJECTIVE: All the conserved regions of HIV gp120 have at least some partial
      homology with human leukocyte antigen (HLA) class I or class II. One functional
      similarity is the ability of gp120 and HLA class II to bind CD4. Given the close
      association between HIV-induced disease and the amount of immune activation and
      anergy, features closely associated with chronic allogenic stimulation, we asked
      whether gp120 shared any other properties of HLA, in this case the ability to
      bind peptides. DESIGN: T-cell epitope peptides known to bind to soluble HLA class
      I or class II were photolabelled and made radioactive. Cross-linking of modified
      peptides to soluble HLA class I, II and gp120 was activated by ultraviolet light
      and analysed by sodium dodecylsulphate-polyacrylamide gel electrophoresis.
      RESULTS: A signal peptide binding to HLA class I and a haemagglutinin peptide
      that binds to HLA class II were found to bind soluble gp120 specifically; binding
      and cross-linking could be competed out with excess of the unmodified peptides
      but not unrelated control peptides. Molecular modelling of gp120 suggests shared
      anchor sites for peptides binding to both HLA and gp120 soluble molecules.
      CONCLUSIONS: The ability to bind these two peptides suggests that gp120 has a
      peptide-binding site of broad specificity, which if functional in vivo, could
      compete with normal peptide loading of major histocompatibility complex (MHC)
      class I and/or class II peptides, as well as aberrantly stimulate the T-cell
      receptor (by virtue of its potential to be mistaken for an allogenic MHC/peptide
      complex), resulting in immune activation, anergy and apoptosis in susceptible
      hosts.

PMID- 8561976
TI  - HIV-1 Tat modulates invasion by a bacterial enteric pathogen into a human
      intestinal cell line.
AB  - OBJECTIVE: To explore the possibility that an HIV-1 gene product may modulate
      entry of an invasive enteric pathogen into a terminally differentiated human
      intestinal cell line. HIV-1 Tat was selected for investigation because of its
      unique ability to cross cell membranes. METHODS: After transient transfection of
      HT29-C1 cells with plasmids containing HIV-1 long terminal repeat (LTR)-lacZ plus
      a Tat expression cassette, or with a pSR-lacZ control plasmid, bacterial invasion
      assays were performed on both groups of cells utilizing a clinical Salmonella
      isolate. Assays were performed concurrently on a control group of non-transfected
      cells. A second series of experiments compared bacterial invasion into cells
      transfected with the Tat expression vector alone versus cells transfected with
      either an isogenic expression vector that did not make Tat, or with pSR-lacZ.
      Finally, the ability of exogenous Tat protein to transactivate an HIV-1 LTR
      chloramphenicol acetyltransferase (CAT) plasmid which had been transfected into
      HT29-C1 cells and to modulate Salmonella invasion was also assessed. RESULTS:
      HT29-C1 cells transfected with a Tat expression vector, either alone or in
      combination with another plasmid, were significantly less susceptible to
      bacterial invasion than cells that either did not undergo transfection, were
      transfected with an otherwise isogenic expression vector without Tat, or
      transfected with an unrelated plasmid. Duplicate experiments also demonstrated
      that exogenous purified Tat protein transactivated an HIV-1 LTR-CAT plasmid which
      had been transfected into HT29-C1 cells and inhibited Salmonella invasion
      compared with unexposed cells. CONCLUSION: HIV-1 Tat inhibits Salmonella invasion
      of a human enterocyte cell line whether the protein is expressed intracellularly
      or provided exogenously.

PMID- 8561977
TI  - Early biopsy versus empiric treatment with delayed biopsy of non-responders in
      suspected HIV-associated cerebral toxoplasmosis: a decision analysis.
AB  - OBJECTIVE: To construct and evaluate a decision analytic model of proposed
      management strategies for HIV-infected patients presenting with cerebral mass
      lesions, radiographically compatible with toxoplasmosis, lymphoma, or other
      etiologies, assuming knowledge of Toxoplasma antibody status in serum. METHODS:
      Using decision analysis, we evaluated two management strategies, for patients
      found to be either Toxoplasma-seropositive or -negative, for whom an initial
      choice was made for early brain biopsy (EB) or for empiric therapy with delayed
      biopsy (ETDB) of non-responders. The outcome to be optimized was the percentage
      of patients alive at 12 months. Model variables included predictive value of
      toxoplasmosis serology, probabilities of treatment response and death within 14
      21 days conditional on correct diagnosis, probability of operative death,
      probabilities of non-diagnostic brain biopsy conditional both on correct
      diagnosis and prior treatment. RESULTS: One and two-way sensitivity analyses, by
      Toxoplasma serostatus, led to the following conclusions (1) for Toxoplasma
      seropositive patients, ETDB gives nearly equivalent outcomes to EB of all
      patients; (2) for Toxoplasma-seronegative patients, although both strategies have
      equivalent outcomes under baseline assumptions, EB is preferred if there are even
      small survival advantages for early versus delayed diagnosis of lymphoma or other
      conditions, or if risk of death within 14-21 days of ET exceeds 10% when correct
      diagnosis is not toxoplasmosis. CONCLUSION: Under plausible assumptions,
      Toxoplasma-seronegative patients will benefit from an early biopsy strategy.

PMID- 8561978
TI  - Autopsy-proven causes of death in HIV-infected patients treated for tuberculosis
      in Abidjan, Cote d'Ivoire.
AB  - OBJECTIVE: To determine autopsy-proven causes of death in HIV-infected patients
      treated for tuberculosis in Abidjan, Cote d'Ivoire. METHODS: A computerized
      listing of 9523 patients diagnosed with tuberculosis and tested for HIV infection
      at Abidjan's two large tuberculosis treatment centers from July 1989 to December
      1991 was matched against a listing of 496 patients who were autopsied in
      Abidjan's largest public hospital in 1991-1992. RESULTS: Fifteen matching
      patients were identified including 11 adults with smear-positive pulmonary
      tuberculosis, three adults with extrapulmonary tuberculosis, and one child with
      smear-negative pulmonary tuberculosis. The autopsy-proven causes of death among
      the adults were tuberculosis (n = 4), bacterial infections (n = 3), cerebral
      toxoplasmosis (n = 2), pulmonary nocardiosis (n = 2), Pneumocystis carinii
      pneumonia (n = 1), atypical mycobacteriosis (n = 1), and wasting syndrome (n =
      1). Tuberculosis was the primary cause of death in two of five smear-positive
      patients who had not completed therapy, in none of the six patients with smear
      positive disease who had completed therapy, and in two of the three patients with
      extrapulmonary tuberculosis. CONCLUSIONS: Chemoprophylaxis with trimethoprim
      sulfamethoxazole (TMP-SMX) might have provided benefit to eight (57%) of the 14
      adults in this series who died either of bacterial infections, toxoplasmosis,
      nocardiosis, or pneumocystosis. Prospective studies are required to elucidate
      further the causes of increased mortality, and to evaluate the benefits of TMP
      SMX prophylaxis in HIV-infected African patients with tuberculosis.

PMID- 8561979
TI  - Prospective study of high grade anal squamous intraepithelial neoplasia in a
      cohort of homosexual men: influence of HIV infection, immunosuppression and human
      papillomavirus infection.
AB  - OBJECTIVE: To determine the risk of developing high grade anal squamous
      intraepithelial neoplasia (HG-AIN) in relation to HIV infection and
      immunosuppression, after controlling for the effects of human papillomavirus
      (HPV) infection. DESIGN: Prospective cohort study of 158 HIV-seropositive and 147
      HIV-seronegative homosexual men presenting to a community-based clinic with
      initially negative anal cytologic and colposcopic findings. METHODS: Subjects
      completed self-administered questionnaires, underwent cytologic screening, and
      standardized unaided and colposcopic examination of the proximal anal canal for
      presence of abnormalities suggestive of AIN. Anal specimens were screened for HPV
      DNA. RESULTS: HG-AIN developed in eight (5.4%) and 24 (15.2%) HIV-seronegative
      and -seropositive men, respectively. Risk of HG-AIN among HIV-seronegative men
      was associated with detection of anal HPV types 16 or 18 by Southern transfer
      hybridization (STH), detection of HPV 16 or 18 at the lower levels by polymerase
      chain reaction but not by STH, and with number of positive HPV tests; HG-AIN risk
      among HIV-seropositive men was associated with detection of HPV 16 or 18 only by
      STH, detection of HPV types other than 16 or 18, CD4 count < or = 500 x 10(6)/l,
      and number of positive HPV tests. HIV-induced immunosuppression remained an
      independent predictor of HG-AIN after adjusting for type and level of detection
      of HPV; HIV infection predicted HG-AIN risk after adjustment for number of
      positive HPV tests. CONCLUSIONS: The association of HG-AIN with HIV, independent
      of HPV type, level of HPV detection and number of positive HPV tests, suggests
      that this increased risk cannot be entirely explained by an effect of HIV on HPV
      detection. Future studies focusing on factors more specific to the local
      microenvironment in the anal canal should help clarify these issues.

PMID- 8561980
TI  - Modelling the impact of alternative HIV intervention strategies in rural Uganda.
AB  - OBJECTIVE: To assess the likely impact on HIV incidence of increased condom use,
      a reduction in casual sexual partners, treatment programmes for other sexually
      transmitted diseases (STD) and combinations of these in rural Uganda. METHODS: A
      simulation model for the transmission dynamics of HIV infection and STD was
      employed, drawing on data from a rural population cohort in South-West Uganda
      with an HIV prevalence of 9% among adults in 1990. RESULTS: For the scenario most
      consistent with data from the study population, 39% of all adult HIV infections
      were averted, in the 10 years from 1990, when condoms were used consistently and
      effectively by 50% of men in their contacts with one-off sexual partners (such as
      bar girls and commercial sex workers). Reducing by 50% the frequency of men's
      sexual contacts with one-off partners averted 68% of infections. Reducing by 50%
      the duration of all STD episodes averted 43% of infections. Combining these three
      interventions averted 82% of all adult infections in the 10 years from 1990.
      CONCLUSION: A substantial proportion of HIV infections may be averted in general
      populations through interventions targeted only on less regular sexual
      partnerships.

PMID- 8561981
TI  - A randomized trial of an education and support program for HIV-infected
      individuals.
AB  - OBJECTIVES: To assess the effectiveness of an intervention for providing
      information and support to HIV-positive donors on changes in their sexual
      behavior, and to assess which donor characteristics are predictive of behavior
      change. DESIGN: Subjects were randomly assigned to a structured intervention or
      community referral group. Follow-up assessments were conducted every 6 months.
      SETTING: New York City, New York, USA. PARTICIPANTS: A cohort of 271 HIV-infected
      persons who donated blood to the New York Blood Center. INTERVENTION: Donors
      randomized to the structured intervention program met individually with a nurse
      for counseling and were offered a six-session support group. The program was
      designed to provide information, encourage safer sexual behavior and provide
      support. MAIN OUTCOME MEASURES: Sexual behavior, psychological distress and
      psychological help seeking, and immune function. RESULTS: In both groups there
      was a large decrease over time in reports of unsafe sexual activity. However,
      more than 30% of participants in both groups reported unsafe sexual activity at
      the 1-year follow-up visit. Donors randomized to the structured intervention
      program did not report significantly more behavior change at the 1-year follow
      up. CONCLUSIONS: Better programs to promote behavior change in seropositive
      individuals are needed.

PMID- 8561983
TI  - Tolerance of a triple combination therapy with zidovudine, didanosine and
      interferon-alpha in seven HIV-infected patients.

PMID- 8561982
TI  - Acceptability of HIV vaccine trials in high-risk heterosexual cohorts in Mombasa,
      Kenya.
AB  - OBJECTIVES: To ascertain the level of acceptance of a prophylactic HIV vaccine
      trial in high-risk HIV-seronegative heterosexual cohorts of men and women in
      Mombasa, Kenya, and to assess the anticipated effects of participation on risk
      behavior. METHODS: Standardized questionnaire administered to a convenience
      sample of commercial sex workers and trucking company employees enrolled in
      prospective cohort studies. RESULTS: Ninety-six per cent of respondents believed
      that HIV was a major problem in Kenya and 86% of men and 94% of women perceived
      themselves at risk. One hundred per cent of women and 84% of men expressed
      interest in participation in an HIV vaccine trial, after explanation of the
      experimental nature of the vaccine, double-blind placebo-controlled design,
      prolonged follow-up and potential change in serostatus. Seventeen per cent of men
      and 9% of women anticipated an increase in risk behavior as a result of
      participation. CONCLUSION: The majority of individuals in two high-risk cohorts
      were interested in participating in Phase III efficacy trials of HIV vaccines. A
      significant minority anticipated an increase in risk behavior, which emphasizes
      the need for intensive counseling and education throughout a vaccine trial.

PMID- 8561984
TI  - Weekly fluconazole for the suppression of recurrent thrush in HIV-seropositive
      patients: impact on the incidence of disseminated cryptococcal infection.

PMID- 8561985
TI  - Cluster of HIV-2 infections among older male bisexuals in Gipuzkoa, Basque
      Country, Spain.

PMID- 8561986
TI  - Serum and saliva immunoglobulin A concentrations show an inverse relationship in
      HIV infection and AIDS.

PMID- 8561987
TI  - Tuberculin reaction size in patients infected with HIV.

PMID- 8561988
TI  - Hydroxyurea and HIV-1 viraemia.

PMID- 8561989
TI  - Risk factors and patterns of HIV-1 transmission in the El Salvador military
      during war time.

PMID- 8561991
TI  - Retrospective versus prospective estimates of number of sexual partners.

PMID- 8561990
TI  - Smoking marijuana before sex: a high-risk behavior in Jamaica?

PMID- 8561992
TI  - Sex hormones as a cofactor in the pathogenesis of epidemic Kaposi's sarcoma.

PMID- 8561993
TI  - Statistics from the World Health Organization.

PMID- 8561994
TI  - Collaborative AIDS prevention research in the developing world: the CAPS
      experience.
AB  - BACKGROUND: Prevention through behavior change is the only way to control the
      spread of HIV infection in the developing world. Success in prevention requires
      consistent and persistent intervention over time, a clear understanding of the
      realities of target populations and involvement of members of these populations
      in prevention efforts. Applied local research is urgently needed, especially in
      the developing world, to design interventions that meet these criteria and to
      test their effectiveness. CENTER FOR AIDS PREVENTION STUDIES (CAPS) MODEL OF
      INTERNATIONAL COLLABORATIVE RESEARCH: Each year, eight to 10 scientists from
      developing countries visit CAPS in San Francisco for 10 weeks of intensive
      learning and collaboration. The main emphasis is on designing a protocol for a
      research project related to AIDS prevention in the visiting scientist's home
      country. CAPS provides pilot study funding and technical assistance to implement
      the project. RESULTS: The quality of the resulting collaborative research is
      represented by the articles published in this volume and by the many alumni of
      the program who have undertaken additional research projects and/or assumed
      leadership positions in AIDS control efforts in their countries.

PMID- 8561995
TI  - AIDS prevention research in the developing world.

PMID- 8561996
TI  - Female partners of AIDS patients in Uganda: reported knowledge, perceptions and
      plans.
AB  - OBJECTIVE: To assess reported knowledge of a partner's AIDS diagnosis, perceived
      risk of HIV infection, need for HIV testing and future support plans among women
      partners of male Ugandan AIDS patients. SUBJECTS AND METHODS: A cross-sectional
      descriptive survey was conducted at New Mulago Hospital, Kampala, Uganda. The
      subjects were women partners of consecutive male AIDS patients admitted to
      medical wards. RESULTS: Only 12% reported their partner's AIDS diagnosis; women
      who reported knowing were less likely to be financially dependent on the partner.
      Most women (76%) reported being at risk of HIV; in general, these women were
      older, in a newer relationship, had less children and were in customary rather
      than civil or cohabiting marriages. More than half (56%) of the women reported a
      need for HIV testing, though few (5%) had been tested. Those who stated the need
      for HIV testing were in a newer relationship, had less children and were more
      financially independent of their husbands; women in a cohabiting type marriage
      were less likely to report their need for testing than those in a civil or
      customary marriage. About half (56%) reported plans for future support if their
      husbands did not recover; these women were more likely to be in an older
      relationship and to have more children. CONCLUSIONS: Most women partners of AIDS
      patients in New Mulago Hospital reported no knowledge of their husbands'
      diagnosis. Over half perceived a need to be tested but very few reported having
      been tested, and only half reported having planned for the future of their
      families. Interventions are urgently needed to address barriers to knowledge and
      to acknowledgement of a partner's AIDS diagnosis, to HIV testing and to planning
      for the future.

PMID- 8561998
TI  - Socioeconomic status and risk of HIV-1, syphilis and hepatitis B infection among
      sex workers in Sao Paulo State, Brazil. Instituto Adolfo Lutz Study Group.
AB  - OBJECTIVES: To determine how HIV risk behavior and the prevalences of sexually
      transmitted diseases vary according to socioeconomic status and city among sex
      workers in Sao Paulo State, Brazil. SUBJECTS AND METHODS: A cross-sectional study
      of 600 female sex workers (100 of a higher socioeconomic status and 100 of a
      lower socioeconomic status in each city) was conducted in the cities of Sao
      Paulo, Campinas and Santos. HIV risk behavior was assessed by questionnaire;
      serological tests were administered to assess prior exposure to HIV-1, syphilis
      and hepatitis B. RESULTS: Only statistically significant (P < 0.05) findings are
      reported here. Compared to those with a higher socioeconomic status, sex workers
      with a lower socioeconomic status worked longer hours each day (9.6 versus 7.9),
      had more clients per day (5.4 versus 2.6) and had fewer episodes of intercourse
      per client per encounter (1.1 versus 1.4). Levels of condom use for vaginal, anal
      and oral sex were significantly higher in Santos than in Sao Paulo or Campinas.
      Twenty-three per cent of the women said they feared violence if they insisted
      that their clients wear condoms; 74% voiced similar fears regarding their non
      client sexual partners. Overall, 11% of sex workers were positive for exposure to
      HIV-1, 45% for syphilis and 39% for hepatitis B. Those with a lower socioeconomic
      status were more likely than those with a higher socioeconomic status to be
      infected with HIV-1 (17 versus 4%), syphilis (66 versus 24%) and hepatitis B (52
      versus 26%), but there were no differences in prevalence rates by city.
      CONCLUSIONS: These data demonstrate substantial heterogeneity in HIV risk
      behavior and the prevalence of HIV-1 and other sexually transmitted diseases
      among sex workers in Sao Paulo State, many of which were related to differences
      in socioeconomic status. Interventions to prevent HIV transmission among sex
      workers must be tailored to the local environment and, in particular, to the
      socioeconomic status of these workers.

PMID- 8561997
TI  - Impact of an intervention on HIV, sexually transmitted diseases, and condom use
      among sex workers in Bombay, India.
AB  - OBJECTIVE: To develop and test an HIV intervention targeting sex workers and
      madams in the brothels of Bombay. SUBJECTS AND METHODS: In a controlled
      intervention trial, with measurements before and after the intervention, 334 sex
      workers and 20 madams were recruited from an intervention site, and 207 and 17,
      respectively, from a similar control site, both in red-light areas of Bombay. All
      sex workers were tested for antibodies to HIV and syphilis, and for hepatitis B
      surface antigen. Information on sexual practices, condom use and knowledge of HIV
      was collected by interviewer-administered questionnaire. All subjects in the
      intervention group underwent a 6-month program of educational videos, small group
      discussions and pictorial educational materials; free condoms were also
      distributed. The blood tests and the questionnaire were readministered to all
      subjects at both sites immediately after the intervention. Both groups were
      followed for approximately 1 year. RESULTS: The baseline level of knowledge about
      HIV and experience with condoms was extremely low among both sex workers and
      madams. The baseline prevalence of HIV antibodies was 47% in the intervention
      group and 41% in the control group (P = 0.17). The incidence densities for HIV
      and sexually transmitted diseases were significantly different in the two groups
      (all P < 0.005): 0.05 and 0.16 per person-year of follow-up for HIV, 0.08 and
      0.22 per person-year for antibodies to syphilis, and 0.04 and 0.12 per person
      year for hepatitis B surface antigen in the intervention and control women,
      respectively. Following the intervention, women reported increased levels of
      condom use, and some (41%) said they were willing to refuse clients who wouldn't
      use them. However, both the sex workers and the madams were concerned about
      losing business if condom use was insisted upon. CONCLUSIONS: Both HIV prevalence
      and incidence are alarmingly high among female sex workers in Bombay. Successful
      interventions can be developed for these women, and even a partial increase in
      condom use may decrease the transmission of HIV and sexually transmitted
      diseases. Intervention programs of longer duration that target madams and clients
      and make condoms easily available are urgently needed at multiple sites in red
      light areas.

PMID- 8561999
TI  - AIDS risk-taking behavior during carnival in Sao Paulo, Brazil.
AB  - OBJECTIVE: The Brazilian Carnival is thought to be a time when the risk of HIV
      infection is likely to be high. We therefore compared the risk during Carnival to
      risk in the past month among male samba school participants in Sao Paulo, Brazil.
      SUBJECTS AND METHODS: A cross-sectional study was conducted among 380 male samba
      school drummers randomly sampled during rehearsal for the 1993 Carnival in Sao
      Paulo by means of a 20-min interviewer-administered questionnaire. The main
      outcome variable was condom use with non-steady partners. RESULTS: The sexual
      behavior of 36.1% of subjects risked HIV infection, but only 9.7% of all subjects
      were at risk only during Carnival. Subjects with a sexual risk of HIV differed
      from those without risk in substance use, attitudes towards condoms and
      expectations about Carnival; those who were at risk only during Carnival did not
      differ from those who were at risk at other times. About half of the subjects had
      been given free condoms during Carnival, although few of the men at risk had
      actually used them. CONCLUSIONS: Though more than a third of the drummers were at
      risk of HIV infection, only a small per cent were at risk only during Carnival.
      The level of sexual risk of HIV infection is probably better explained by factors
      in the men's daily lives, rather than through information on risks taken during
      Carnival. These results raise questions concerning the efficacy of universal
      condom distribution during Carnival, since about half of the men were given
      condoms but few of those at risk actually used them. A targeted distribution of
      condoms to populations with a high demonstrated risk may be more effective in
      preventing new HIV infection.

PMID- 8562000
TI  - A family planning intervention to reduce vertical transmission of HIV in Rwanda.
AB  - OBJECTIVES: Since contraception is an effective way of preventing the vertical
      transmission of HIV, we evaluated the impact of a family planning intervention on
      hormonal contraceptive use and incident pregnancy in a group of HIV-positive and
      HIV-negative urban Rwandan women. SUBJECTS AND METHODS: In a longitudinal cohort
      study, 502 women who were not pregnant or infertile and who had been previously
      HIV tested and counseled viewed an informational video about hormonal
      contraception followed by a facilitated discussion. They were given access to
      oral or injectable hormonal contraception and Norplant at the research clinic;
      those who used these methods were seen every 3 months. RESULTS: Of the 330 HIV
      positive and 172 HIV-negative women who underwent the intervention, 120 either
      became new hormonal method users (n = 40), continued their previous use of a
      hormonal method (n = 64), or switched to another hormonal method (n = 16)
      following the intervention. There was a shift to use of longer lasting hormonal
      methods, and the annualized attrition rate was < 15%, compared to > 50% prior to
      the intervention. Rates of oral and injectable contraceptive use were similar
      among HIV-positive and HIV-negative women. Nine per cent of HIV-positive women
      became pregnant in the year after the intervention compared to 22% in a prior 12
      month period when contraceptives were not provided at the study site. The
      corresponding proportions for HIV-negative women were 20% after the intervention
      versus 30% before the intervention. CONCLUSIONS: Access to and information about
      hormonal contraceptives resulted in increased use and reduced attrition among
      both HIV-positive and HIV-negative women in this study. The reduction in incident
      pregnancy was greatest among HIV-positive women, suggesting that factors other
      than access to hormonal contraceptives may have influenced fertility outcomes.
      Knowledge of HIV serostatus may have an important influence on family planning
      decisions.

PMID- 8562001
TI  - Adolescent sexuality in Saint Petersburg, Russia.
AB  - OBJECTIVES: To describe adolescent knowledge, attitudes and behavior relevant to
      sexuality and the prevention of AIDS in Saint Petersburg, Russia. SUBJECTS AND
      METHODS: A cross-sectional descriptive study was designed, taking a random sample
      of 10th grade students at 14 Saint Petersburg grade schools, which were
      stratified by socio-economic district. A total of 185 female and 185 male
      students completed a self-administered 46-item questionnaire, with a response
      rate of 94%. RESULTS: From the questionnaires, 20% of females and 31% of males
      reported having had sexual intercourse and 25% of females and 12% of males
      reported being sexually abused. These adolescents displayed much misinformation
      about sexual matters and AIDS prevention. Only 25% of the females and 34% of the
      males believed that condoms should be used just once, and 38% of each sex
      believed that if washed, they could be used multiple times. Many respondents,
      especially males, rated their knowledge about sexual matters as high or adequate.
      Support for sex education was strong, especially among females, and respondents
      generally saw sex education as improving sexual pleasure. Most information
      sources about sexual activity were either not considered very credible, or not
      adequately accessible. CONCLUSIONS: Substantial reported rates of sexual abuse,
      sexual experience and much misinformation and unwarranted attitudes toward
      condoms, safer sexual practices and HIV/AIDS suggest the need for vigorous sex
      education programs for Russian youth. The early and sustained education of girls
      is especially important. Sex education should be introduced at an early age so
      that children can be taught how to reduce the risks of sexual abuse, HIV
      infection and other sexually transmitted diseases, and to improve their sexual
      experiences as responsible adults.

PMID- 8562002
TI  - 'Dry sex' and HIV infection among women attending a sexually transmitted diseases
      clinic in Lusaka, Zambia.
AB  - OBJECTIVES: To describe 'dry sex' practices intended to decrease vaginal
      secretions and to determine whether these practices are related to HIV infection.
      SUBJECTS AND METHODS: A cross-sectional study was conducted in a sexually
      transmitted diseases clinic in a teaching hospital in Lusaka, Zambia. The
      subjects comprised 329 women aged 15-50 years presenting consecutively for an
      initial evaluation of sexually transmitted disease symptoms. Dry sex practices
      were assessed by questionnaire, and serological testing for HIV antibodies was
      performed. RESULTS: Fifty percent of women had engaged in at least one dry sex
      practice. The most common practices were drinking 'porridge' (a liquid or
      suspension believed to cause drying of the vagina; 28%), removing vaginal
      secretions with a cloth (22%) and placing leaves in the vagina (11%). The most
      frequent reasons given for drinking porridge were to increase the partner's
      sexual enjoyment and to tighten the vagina, while cleaning the vagina was
      mentioned often by those using cloth or leaves. Swelling or peeling of the vagina
      was reported by approximately 10% of women using cloth or leaves. Overall, the
      HIV seroprevalence in the sample was 58%. In bivariate analysis, no practice was
      statistically significantly associated with HIV infection. Multiple logistic
      regression had little impact on these findings. CONCLUSIONS: Although a variety
      of practices with potential relevance to HIV transmission were reported, there
      was no evidence in this study population of a strong relationship between these
      practices and HIV infection. Women should be counseled about the potential risks
      of these practices, but prevention efforts should continue to emphasize measures
      of known effectiveness, particularly limiting the numbers of sexual partners,
      consistently using condoms and obtaining appropriate treatment for sexually
      transmitted diseases.

PMID- 8562003
TI  - 'Superstar' and 'model brothel': developing and evaluating a condom promotion
      program for sex establishments in Chiang Mai, Thailand.
AB  - OBJECTIVES: We developed and evaluated a multifaceted AIDS prevention program to
      increase condom use among sex workers in the city of Chiang Mai, Northern
      Thailand. SUBJECTS AND METHODS: A year-long intervention targeted sex workers,
      brothel owners and clients, promoted cooperation between these groups and the
      public health office and established a free condom supply for sex establishments.
      Nearly 500 women from 43 establishments took part in the program, encompassing
      nearly all direct sex workers in urban Chiang Mai. The intervention included
      repeated small-group training sessions for sex workers in which experienced women
      ('superstars') acted as peer educators. The 'model brothel' component encouraged
      all brothel owners in Chiang Mai to insist on mandatory use of condoms by sex
      workers and to encourage clients to use condoms. Before and after the
      intervention, specially trained volunteers posing as clients tested a subsample
      of sex workers to see whether they insisted on condom use. RESULTS: The
      intervention was well received by sex workers and obtained strong support and
      cooperation from brothel owners. Before the intervention, only 42% (10/24) of
      women surveyed by volunteers posing as clients refused to have sex without a
      condom, even when the client insisted and offered to pay three times the usual
      fee. Following the program, 92% (72/78) refused; 1 year later, 78% (69/85)
      refused during the same scenario. CONCLUSIONS: An innovative program directly
      involving sex workers as peer educators and enlisting the support of brothel
      owners and operators can result in improved condom use over time. Lessons learned
      from this program may be applicable elsewhere.

PMID- 8562004
TI  - Results of a model AIDS prevention program for high school students in the
      Philippines.
AB  - OBJECTIVES: To describe the sexual practices of high school students; to describe
      the process of development of a school-based AIDS prevention program; and to
      evaluate the effect of this program on students' AIDS-related knowledge,
      attitudes and AIDS-preventive behaviors. SUBJECTS AND METHODS: A cluster
      randomized, controlled trial with pretest/post-test evaluation was conducted in
      four demographically similar public high schools in a semi-urban district of
      Metro Manila, the Philippines. Of 845 high school students who participated in
      the baseline survey, 804 (95%) completed a postintervention questionnaire.
      INTERVENTION: An AIDS prevention program was developed by public high school
      teachers together with local AIDS experts, social scientists and health
      educators. The teacher-led AIDS program was designed to provide students with
      accurate information about AIDS, particularly in dispelling misconceptions about
      casual contagion, to foster positive attitudes towards people with AIDS and to
      develop skills aimed at clarifying values and assessing intended behavior.
      RESULTS: At baseline, 11% of students (20% of males and 4% of females) reported
      ever having had sexual intercourse (mean age 14 years). Among these, condom use
      was low (24%). After implementation of the AIDS prevention program, statistically
      significant effects favoring the intervention group were observed in knowledge
      and attitudes towards people with AIDS. While there was no statistically
      significant overall effect on intended preventive behavior, the program appeared
      to delay the students' intended onset of sexual activity. CONCLUSIONS: A sizable
      number of Filipino high school students are sexually active but condom use is
      low. School-based AIDS prevention programs can be developed and implemented in
      developing countries with the assistance of school personnel to address sexual
      issues. Our program was successful in increasing AIDS-related knowledge and
      improving attitudes towards people with AIDS. Supplementation with other
      preventive activities may be needed to achieve lasting changes in students' risk
      taking behavior.

PMID- 8562005
TI  - Transduction in microbial biosensors using multiplexed bioluminescence.
AB  - The enormous diversity of genetic responses in living microbes to their
      environment is an attractive resource on which to base biosensor designs. In
      particular, there is much interest in microbial sensors for environmental
      monitoring where toxicity can be ascertained directly by its action on cellular
      physiology. However, due to the complexities of living systems, the utility of
      genetic-based microbial sensors has been limited by the ability to accurately
      transduce the activities of specific genetic sensing systems into readily
      measurable signals. We present here a strategy for employing an additional signal
      in the sensor design, to provide an internal baseline control upon which to
      reliably interpret sensor responses. The strategy relies on using beetle
      luciferases capable of emitting optical signals of different wavelengths; the
      optical signals are a sensitive real-time indicator of genetic activity within
      the cells. The different wavelengths allow both a target and control signal to be
      incorporated into each cell, providing a means of differentiating between
      specific effects of a genetic sensing system and other non-specific interfering
      influences.

PMID- 8562006
TI  - Poly(methylene blue)-modified thick-film gold electrodes for the electrocatalytic
      oxidation of NADH and their application in glucose biosensors.
AB  - Electropolymerization of the phenothiazine derivative methylene blue (MB) on
      screen-printed, thick-film gold electrodes leads to electrocatalytically active
      and conducting layers of poly(methylene blue) (PMB) in intimate and stable
      contact with the electrode surface. The catalytic properties of the PMB films
      allow anodic oxidation of NADH at potentials as low as +200 mV vs. the saturated
      calomel electrode (SCE) reducing interferences from cooxidizable species as well
      as minimizing electrode fouling by enabling a simultaneous two-electron transfer
      mechanism. Dehydrogenase-based biosensors employing PMB-modified thick-film
      electrodes are obtained either by entrapment of the enzyme into the PMB layer
      itself or by laminating an enzyme membrane made of an aqueous poly(vinylacetate)
      dispersion over the PMB-modified electrode. Both methods are used to fabricate
      glucose biosensors which can be operated at low overpotentials, i.e. +200 mV vs.
      SCE.

PMID- 8562007
TI  - A vibrating probe thermal biochemical sensor.
AB  - Rapid vibration of small enzyme-thermopile biochemical sensors in solution has
      been observed to substantially improve their thermal noise rejection. Millimeter
      order 20 Hz vibratory excursions of a thermal biosensor by a piezoelectric bender
      element were found to be effective in eliminating the need for temperature
      controlled dewars, flow streams, or special thermal environments ordinarily
      required to operate these sensors. Vibrated thermopiles have been made into
      biochemical sensors by attaching thin membrane hollow fibers to the thermopile
      sensing region and perfusing the lumen of the fiber with small quantities of an
      enzyme solution. This process can give the biosensor an extended lifetime by
      allowing easy replacement of the enzyme. Vibrated enzyme-thermopile biochemical
      sensors can be realized in a convenient and compact probe-type configuration that
      is directly immersible into a test solution.

PMID- 8562008
TI  - Determination of glutamine and glutamic acid in mammalian cell cultures using
      tetrathiafulvalene modified enzyme electrodes.
AB  - Tetrathiafulvalene (TTF) mediated amperometric enzyme electrodes have been
      developed for the monitoring of L-glutamine and L-glutamic acid in growing
      mammalian cell cultures. The detection of glutamine was accomplished by a coupled
      enzyme system comprised of glutaminase plus glutamate oxidase, while the
      detection of glutamic acid was carried out by a single enzyme, glutamate oxidase.
      The appropriate enzyme(s) were immoblized on the Triton-X treated surface of
      tetrathiafulvalene modified carbon paste electrodes by adsorption, in conjunction
      with entrapment by an electrochemically deposited copolymer film of 1,3
      phenylenediamine and resorcinol. Operating conditions for the glutamine enzyme
      electrode were optimized with respect to the amount of enzymes immoblized, pH,
      temperature and mobile phase flow rate for operation in a flow injection (FIA)
      system. When applied to glutamine and glutamic acid measurements in mammalian
      cell culture in FIA, the results obtained with enzyme electrodes were in
      excellent agreement with those determined by enzymatic analysis.

PMID- 8562009
TI  - Anionic biopolymers as blood flow sensors.
AB  - The finding of flow-dependent vasodilation rests on the basic observation that
      with an increase in blood flow the vessels become wider, with a decrease the
      vascular smooth muscle cells contract. Proteoheparan sulphate could be the sensor
      macromolecule at the endothelial cell membrane-blood interface, that reacts on
      the shear stress generated by the flowing blood, and that informs and regulates
      the vascular smooth muscle cells via a signal transduction chain. This anionic
      biopolyelectrolyte possesses viscoelastic and specific ion binding properties
      which allow a change of its configuration in dependence on shear stress and
      electrostatic charge density. The blood flow sensor undergoes a conformational
      transition from a random coil to an extended filamentous state with increasing
      flow, whereby Na+ ions from the blood are bound. Owing to the intramolecular
      elastic recoil forces of proteoheparan sulphate the slowing of a flow rate causes
      an entropic coiling, the expulsion of Na+ ions and thus an interruption of the
      signal chain. Under physiological conditions, the conformation and Na+ binding
      proved to be extremely Ca(2+)-sensitive while K+ and Mg2+ ions play a minor role
      for the susceptibility of the sensor. Via counterion migration of the bound Na+
      ions along the sensor glycosaminoglycan side chains and following Na+ passage
      through an unspecific ion channel in the endothelial cell membrane, the signal
      transduction chain leads to a membrane depolarization with Ca2+ influx into the
      cells. This stimulates the EDRF/NO production and release from the endothelial
      cells. The consequence is vasodilation.

PMID- 8562010
TI  - The critical sensor: a new type of evanescent wave immunosensor.
AB  - A new planar waveguide immunosensor has been developed in which adsorption at a
      surface, changing the refractive index contrast, is measured. In this "critical"
      sensor the change in the effective refractive index contrast is transducted to a
      shift of the critical reflection angle. The sensor's theoretically. In addition,
      an experimental sensitivity evaluation on the basis of several immunosensing
      experiments is presented. The obtained lower detection limit is 2 x 10(-2) nm in
      adlayer growth, equivalent to 12 pg/mm2 of analyte coverage. This sensitivity is
      comparable to the performance of the surface plasmon resonance sensors or the
      grating coupler sensors. However, the "critical" sensor has some advantages.
      These are mainly the ease of fabrication and adjustment prior to a measurement,
      and the fact that for an experiment no metal layer has to be used.

PMID- 8562011
TI  - Glucose oxidase mediation by soluble and immobilized electroactive detergents.
AB  - A series of novel, surface-active, inorganometallic complexes of osmium were
      synthesized and then characterized (using electrochemical techniques) as electron
      transfer mediators for glucose oxidase (EC 1.1.3.4, GOD) from Aspergillus niger.
      The mediators contain a dipyridylamine ligand bearing (on the amine nitrogen) a
      saturated alkyl chain (typically C5 to C12), omega-terminated with either a
      methyl group or a functional group such as carboxyl or hydroxyl. Such compounds
      displayed subtle differences in their interactions with GOD. The presence of a
      omega-functional group tended to diminish a mediator's micelle-forming activity,
      but also concomitantly decreased the denaturing action of the mediator towards
      the protein structure of GOD. However, the presence of an ionised carboxyl group
      slowed GOD mediation relative to that of a similar mediator bearing a methyl
      terminated long alkyl chain, probably because of the additional negative charge.
      The omega-carboxyl functionality allowed covalent coupling of mediators to NH2
      bearing graphite electrodes. GOD was co-immobilized and the resulting,
      reagentless, glucose-sensitive electrodes were characterized. Immobilization of
      the mediator did not appear to affect unduly the ability to mediate GOD.
      Additionally, complexes were directly coupled to lysine groups of GOD to give a
      self-mediating enzyme.

PMID- 8562012
TI  - Retention of bacteriorhodopsin activity in dried sol-gel glass.
AB  - The D96N mutant form of bacteriorhodopsin (bR) purple membrane fragments isolated
      from Halobacterium salinarium has been entrapped in sol-gel glass and dried. The
      photo-activity of the bR was monitored during drying over a period of 60 days.
      The entrapped bR was initially dried at 4 degrees C followed by room temperature
      storage. Samples showing constant activity after storage at 4 degrees C lost
      further activity at room temperature, eventually reaching a level where the
      activity remained constant. Upon further drying at 100 degrees in a vacuum oven
      the glass lost an additional 11.4 +/- 1.3% weight and all remaining activity.

PMID- 8562013
TI  - [Stereoselective analysis of pharmaceutical compounds in biological fluids with
      capillary electrophoresis].
AB  - Biological fluids drugs analysis are important to investigate the pharmacokinetic
      and pharmacodynamic of the subministered compounds for the comprehension of their
      behaviour and bioavailability. Many pharmaceutical preparations contain a chiral
      molecule as active compound often as racemic mixture of the two enantiomers of
      which only one exhibits pharmacological effect, the other enantiomer being
      inactive or responsible of toxicological effects. In fact two enantiomers with
      almost identical physical and chemical properties can exhibit a different
      behaviour in an highly stereoselective environment as the human body. With
      respect to the analytical methods in use for chiral separation Capillary
      Electrophoresis shows high efficiency and resolution together with feasibility,
      low costs and very short analysis time. CE and MEKC have been used for
      enantiomers resolution of antihypertensive and anticoagulant drugs in body
      fluids. By cyclodextrin modified MECK the separation of mephenytoin and 4
      hydroxymephenytoin metabolite in urine samples has been performed in order to
      identify different phenotypes in the oxidative metabolising ability in man.

PMID- 8562014
TI  - Renin inhibitors containing nicotinic or isonicotinic acid at the N-terminus.
      Part V.
AB  - Four new compounds: Nic-Phe/4-OMe/-MePhe-Sta-epsilonAhx-OMe/23/,Nic-Phe/4-OMe/
      MePhe- Sta-epsilonAhx-Iaa/24/,iNic-Phe/4-OMe/-MeLeu-Sta-ep silonAhx-OMe/29/ and
      iNic-Phe/4-OMe/-MeLeu-Sta-epsilonAhx-Iaa/30/ have been synthesized in search
      after renin inhibitors of improved biological properties. Their stability against
      chymotrypsin activity, solubility in water at pH 7.4, 6.9 and 2.0, partition
      coefficient and activity in vitro were determined. All synthesized inhibitors are
      resistant to enzymatic degradation, all are very good soluble in water at pH 2.0,
      poorly soluble at pH 6.9 and insoluble at pH 7.4. Partition coefficients go up
      together with increase of pH worth of buffer. IC50 of obtained inhibitors
      23,24,29 and 30 is 3 x 10(-4),7.5 x 10(-4),4 x 10(5) and 4 x 10(-3)M/1
      respectively.

PMID- 8562015
TI  - In vitro keratinocytes responses to chemical allergens.
AB  - An early event during the induction of skin sensitization is the production by
      keratinocytes (kc) of cytokines. Considering the role of kc in skin inflammatory
      and immune responses, we investigated the effect of three skin allergens
      (oxazolone, nickel sulfate and mixture of methyisothiazolinone and
      methylcholoisothiazolone) on IL-1 alpha production by a murine kc cell line
      (HEL30). Confluent cells were treated for different times with various
      concentrations of oxazolone, NiSO4 and mixture of methyisothiazolinone and
      methylcholoisothiazolone. IL-1 alpha was measured by ELISA both in conditioned
      media and cell-associated. All chemicals were able to induce a dose-response
      production of IL-1 alpha. This increase was related to an increase in protein
      synthesis as measured by 3H-leucine incorporation. At high concentrations all
      chemicals were cytotoxic as measured by LDH release. In the same cell system we
      also measured the effect of lanolin, a non irritant compound, on IL-1 alpha
      release. Even at the concentration of 300 micrograms/ml no IL-1 alpha release
      could be detected in the conditioned media. We have previously found a good rank
      correlation between in vitro surfactants induced IL-1 alpha release and in vivo
      Draize test. We now extend the possibility to use IL-1 alpha production for
      preliminary screening of chemicals for their irritative/allergenic potential,
      reducing the need for in vivo models.

PMID- 8562016
TI  - Dextran as protectant against damage caused by sparging for hybridoma cells in a
      bubble column.
AB  - The effect of the addition of dextran as a protective polymer against sparging
      was examined with hybridoma suspension cells in a bubble column under
      standardized conditions. The protective effect of high concentrations of high
      molecular weight dextran showed a correlation with the bulk viscosity of the
      medium. A distinct protective effect occurs at viscosities greater than 20 x 10(
      3) Pa s-1. In contrast, low molecular weight dextrans that cause a minor increase
      in viscosity, also provide no protection against sparging. There is no strict
      correlation between surface tension and the protective effect of dextran against
      sparging. Oxygen transfer is strongly reduced by high concentrations of high
      molecular weight dextran. Therefore, addition of dextran as protective polymer
      against sparging for large-scale production processes with animal cells in
      stirred reactors does not seem feasible.

PMID- 8562017
TI  - A new balance equation of reducing equivalents for data consistency check and
      bioprocess calculation.
AB  - The reducing equivalent (RE) balance is a basic equation for data consistency
      check and calculations of bioprocesses. The macroscopic approach is often used
      because it does not require detailed knowledge of metabolic pathways. In this
      work, the conventional Minkevich-Eroshin balance equation is examined with data
      of anaerobic glycerol conversion by Klebsiella pneumoniae and Clostridium
      butyricum as examples. It is shown that the Minkevich-Eroshin equation is very
      insensitive to measurement errors in products of less dominance and/or with
      relatively low reductance degree. Relatively large deviations from experimental
      values are encountered when the Minkevich-Eroshin equation is used for the
      calculations of these products. To overcome some of these shortcomings an
      improved RE balance equation is proposed that is based on 'reductance equations'
      of substrate conversion into the individual carbon containing products (including
      biomass). The proposed new equation significantly improves the performance of the
      RE balance equation for data consistency check and for the calculations of
      unknown variables with relatively low reductance degree. The rationale for this
      is that it considers merely the REs that really participate in the bioreactions.
      The use of the proposed method requires no detailed knowledge of metabolic
      pathways and is therefore of macroscopic nature. It can be reduced to the pathway
      balance equation if the pathways are known.

PMID- 8562019
TI  - Amplification of lambda plasmids in Escherichia coli relA mutants.
AB  - It was previously demonstrated that, contrary to wild-type stringent (rel+)
      strains of Escherichia coli, in amino acid-starved relaxed (relA) mutants the
      replication of lambda plasmid proceeds for several hours. The replication leads
      to amplification of lambda plasmid DNA. Here, the conditions for this
      amplification have been optimized. The amplification efficiency depends on the
      temperature as well as on the nature of amino acid starvation, but it is only
      little or totally not dependent on the pH value of the medium in a range from 6.0
      to 8.0. It seems that the most efficient amplification can be achieved by
      overnight cultivation of E. coli relA arg strain harbouring lambda plasmid at 36
      39 degrees C in minimal medium containing Casamino acids. Under these conditions,
      the copy number of lambda plasmid increases from about 40 to about 300 per cell
      giving greater than 7-fold amplification.

PMID- 8562018
TI  - Use of the Escherichia coli chromosomal DHFR gene as selection marker in
      mammalian cells.
AB  - The folA gene, the chromosomal dhfr gene of Escherichia coli, was engineered for
      expression in mammalian cells. In contrast to plasmid-derived bacterial dhfr
      genes previously used as selection markers in mammalian cells, the folA gene
      product is inhibitable by methotrexate (MTX) and trimethoprim (TMP). Therefore,
      this dhfr may present an alternative to mammalian dhfr species currently used as
      amplifiable selection markers. Transfected E. coli folA dhfr could complement the
      lack of endogenous DHFR in Chinese hamster ovary (CHO) cells lacking a functional
      dhfr gene. Both MTX and TMP inhibited growth of E. coli folA dhfr-transfected CHO
      cells. Expression of E. coli folA DHFR could be visualized by incubating the
      transfected cells with a fluorescent methotrexate derivative (F-MTX). Binding of
      F-MTX to E. coli folA DHFR was inhibitable as by both MTX and TMP, whereas MTX
      but not TMP blocked binding of F-MTX to recombinant mouse DHFR.

PMID- 8562020
TI  - Measurements of sulfur, phosphorus and other ions in microbial biomass: influence
      on correct determination of elemental composition and degree of reduction.
AB  - The elemental composition of microorganisms varies widely with respect to the N,
      S, P and ash content as well as many trace elements depending on microorganism
      and growth conditions. As a consequence, the mass of 1 C-mol of biomass can
      differ considerably from one microorganism to another. Experimental results show
      that sulfur is completely volatilized during combustion, so that the calculation
      of the mass fraction of oxygen is affected when S is not measured. However, its
      neglect does not seriously affect the elemental composition and the degree of
      reduction of biomass. Phosphorus is found in ash after combustion at the same
      degree of reduction as in biomass. Therefore, oxygen bound to it should be
      included in the elemental formula, so that the degree of reduction of biomass
      remains unchanged by inclusion of P into elemental formula. No external oxygen is
      incorporated into biomass during combustion and thus the measured ash fraction is
      correct.

PMID- 8562021
TI  - Mechanisms of animal cell damage associated with gas bubbles and cell protection
      by medium additives.
AB  - Animal cell damage arising from gas sparging is considered to be a major barrier
      to large-scale production of recombinant biologicals in animal cell culture.
      Understanding sparging cell damage is therefore of significance to the
      application of animal cell culture. The paper reviews the hydrodynamics of bubble
      rupture, mechanisms of cell-bubble interaction, mathematical modelling and
      quantification of the sparging damage. Another interesting topic addressed in the
      paper is the protective effects of various medium additives against fluid
      mechanical cell damage, especially those surface-active polymers such as pluronic
      polyols, methylcellulose and polyethylene glycol. Experimental results obtained
      recently by the author and other researchers were examined to reveal the
      mechanisms of additive protection. The interactions of additives with air-liquid
      interfaces and the animal cells were analyzed with respect to their physical
      properties and chemical structure.

PMID- 8562022
TI  - Threonine dehydratases in different strains of Streptomyces fradiae.
AB  - Among Streptomyces fradiae parent strain (NRRL 2702), aspartate auxotroph strain
      (SMF 305), and revertant strain (SMF 306), the revertant strain is the highest
      producer of tylosin and showed different repression patterns of tylosin
      production by ammonium ion from the parent strain. These results were elucidated
      by the facts that the revertant strain was superior to the parent or auxotroph
      strain in the biosynthesis of glutamine synthetase involved in ammonium
      assimilation and in the biosynthesis of threonine dehydratase (TDT) involved in
      providing precursors necessary for tylosin production, and ammonium ion inhibited
      the activity of TDT purified from the parent strain more than that of TDT from
      the revertant strain. TDT from the parent strain has been purified by DEAE
      cellulose, hydroxyapatite, Mono Q HR 5/5, and reversed-phase Protein C4
      chromatography. The molecular mass was 60 kDa by SDS-PAGE and 240 kDa by gel
      filtration. The N-terminal amino acid sequence of TDT was NH3-E-A-T-G-P-L-T-T-E-S
      G-A-P-V. The activity of TDT was allosterically activated by adenosine
      monophosphate.

PMID- 8562023
TI  - Genetics of IgA deficiency.
AB  - IgA deficiency is the most common humoral defect in man and results in an
      increased susceptibility to respiratory tract and gastrointestinal infections.
      Both clinical and genetic data support a close relationship with common variable
      immunodeficiency, a disease which involves not only IgA and IgG production, but
      also, in half of the patients, IgM. It is likely that the two disorders represent
      an allelic condition with a variable expression of a common gene defect which is
      thought to be involved in the regulation of immunoglobulin class switching. It is
      possible that a single, autosomally inherited gene with a limited penetrance is
      responsible for the development of both these defects.

PMID- 8562024
TI  - Histopathology of postpartum placental sites in mink (Mustela vison) exposed to
      polychlorinated biphenyls or fractions thereof.
AB  - Polychlorinated biphenyls (PCB) cause reproductive failure in mink. Ovulation and
      nidation occur, but the fetuses die during gestation. The toxicity of different
      chlorinated biphenyl (CB) congeners differs markedly. Dioxin-like congeners with
      no (0-ortho CBs) chlorine in the ortho position to the biphenyl bond are
      considered to be highly toxic. Altogether, 13 groups of 10 female mink (Mustela
      vison) were exposed to PCB or CB fractions thereof during the reproductive season
      of 1988 and 1989. In 1988, one group of mink received 2 mg/day of Clophen A50 and
      five groups received single fractions thereof or synthetic 0-ortho CB in their
      diet. In 1989, one group received 1.64 mg/day of Aroclor 1254 and six groups
      received combinations of fractions thereof. The daily amounts of the fractions
      administered per animal were equivalent to those present in 2 mg of Clophen A50
      or 1.64 mg of Aroclor 1254. After administration for 3 months in both
      experiments, the animals were killed 5 days after parturition. Histological
      examination focused on the placental sites. The most involuted placental sites
      were those of early fetal death in primiparous, non-whelping animals in the 1989
      experiment. The least involuted placental sites, displaying a hyperplastic and
      pleomorphic uterine luminal epithelium, in which proliferating cell nuclear
      antigen (PCNA) was present, were those of late fetal death in biparous, non
      whelping animals in the 1988 experiment. The survival of the fetoplacental unit
      was related to PCB exposure. The histology of the placental sites seemed only to
      be related to the survival time of the fetuses and to the number of former
      reproductive seasons.

PMID- 8562025
TI  - Mobilization of annexin V during the uptake of DNP-albumin by human dendritic
      cells.
AB  - Dendritic cells play a crucial role in antigen presentation in various tissues.
      The endocytic capacity of these cells has been regarded as minimal, but recent
      work on dendritic cells from mouse spleen has disclosed that the fluid-phase
      traffic through late endosomes is as active in dendritic cells as in other
      antigen-presenting cell types. We show that cultured human dendritic cells
      express the annexins I, III, IV, V and VI, as detected by immunofluorescence
      staining. The annexins are cytosolic Ca(2+)-dependent proteins with the ability
      to promote vesicle aggregation and membrane fusion through their capacity to bind
      to membrane phospholipids. Annexin I and VI appeared to outline the cytoskeleton
      and the plasma membrane in cultured human dendritic cells. Studies using confocal
      laser scanning microscopy showed that during the endocytosis of fluorescent
      dinitrophenyl-conjugated albumin by dendritic cells, there was a redistribution
      of annexin V which was found to colocalize with vesicles containing dinitrophenyl
      FITC-conjugated albumin.

PMID- 8562026
TI  - A high-affinity soluble folate receptor in fluids of non-neoplastic ovarian
      cysts: radioligand binding, molecular size, hydrophobic residue, and
      immunological properties.
AB  - The presence of a soluble folate receptor in fluids of non-neoplastic ovarian
      cysts was demonstrated. Radioligand binding exhibited characteristics typical of
      high-affinity folate-binding proteins. These included positive cooperativity, a
      tendency to increased binding affinity with decreasing receptor concentration, a
      slow ligand dissociation at pH 7.4 and inhibition by folate analogues. The folate
      receptor was probably synthesized in the lining epithelial cells of the cysts
      which showed positive immunostaining with antibodies against human milk folate
      binding protein. The gel filtration profile of cystic fluid contained two
      radioligand-bound peaks, 25 and 100 kDa, whereas a single band of 70 kDa was seen
      on SDS-PAGE immunoblotting. Treatment with the enzyme phosphatidylinositol
      specific phospholipase C resulted in a partial conversion of the 100 kDa peak to
      the 25 kDa peak. This suggests that insertion of a hydrophobic
      glycosylphosphatidylinositol tail into Triton X-100 micelles could give rise to
      large molecular size forms of the receptor on gel filtration.

PMID- 8562027
TI  - The Legionella micdadei flagellin: expression in Escherichia coli K 12 and DNA
      sequence of the gene.
AB  - To study the structure and function of the Legionella flagellum, we screened a
      genomic L. micdadei library in Escherichia coli for expression of the flagellin
      (Fla) subunit. One recombinant clone, JM105 (pHI5588), producing a truncated Fla
      protein of 40.5 kDa was identified. The plasmid pHI5588 carried a L. micdadei DNA
      insert of 5 kb, containing ca 95% of the fla gene. The complete DNA sequence of
      the L. micdadei fla gene was obtained by combining sequence data from pHI5588
      with results using a polymerase chain reaction-based system for genome walking
      (vectorette PCR). The L. micdadei fla gene shared a high degree of homology with
      other flagellin genes in the amino- and carboxy termini, whereas the central
      region was found to be nonconserved. The fla sequence will facilitate the cloning
      of Fla proteins from other Legionella species and the study of flagella in the
      pathogenesis of Legionnaires' disease.

PMID- 8562028
TI  - An experimental study of gastric stump carcinoma in Wistar rats.
AB  - The risk of gastric stump carcinoma is increased 15-20 years after gastric
      resection for benign disease. Reflux of duodenal juice, bacterial overgrowth and
      formation of N-nitroso compounds are possible etiological factors. There is a
      geographical variation in the incidence of gastric cancer, possibly explained by
      differences in food intake. Experimentally it is possible to induce gastric stump
      carcinoma in rats without the addition of exogenous carcinogens. The aim of this
      study was: 1) to find the incidence of gastric carcinoma in rats subjected to BII
      resection and followed for 10 months, and 2) to examine if acetic acid, a common
      dietary factor, could influence the development of gastric carcinoma. Amongst BII
      operated male Wistar rats, infiltrating carcinoma was found in 5/20 on a normal
      diet and in 5/24 exposed to acetic acid (NS). Benign mucosal changes were seen in
      12/20 and 16/24 respectively (NS). With the exception of a profound inflammation
      in one sham-operated animal, no mucosal pathological changes were found in 24
      sham-operated and 24 control animals where no operation was performed.

PMID- 8562029
TI  - Multiresistance in Staphylococcus spp. blood isolates in Finland with special
      reference to the distribution of the mecA gene among the Staphylococcus
      epidermidis isolates. The Finnish Study Group for Antimicrobial Resistance.
AB  - A total of 570 Staphylococcus spp. blood isolates collected in Finland in 1991
      were tested for susceptiblity to oxacillin and 19 additional antimicrobial
      agents. The Staphylococcus epidermidis isolates were also analyzed for the
      presence of the mecA gene by the polymerase chain reaction (PCR). Of the 238 S.
      epidermidis, 137 (58%) were in vitro identified as methicillin-resistant and 5
      (2%) exhibited oxacillin MICs between 1 and 3 micrograms/ml. All these isolates
      were positive for the mecA gene in PCR as an indication of genetic resistance to
      methicillin, while none of the remaining 96 S. epidermidis isolates (oxacillin
      MICs < or = 0.25 microgram/ml) was positive. Multiresistance was observed in 123
      (87%) of the 142 mecA-positive S. epidermidis. Of the 332 Staphylococcus aureus
      isolates, only one (0.3%) was phenotypically resistant to methicillin; the strain
      was also resistant to three other unrelated classes of antimicrobials. True
      methicillin resistance of this strain was manifested by the presence of the mecA
      gene in PCR. Based on these results, multiresistance was still extremely rate
      among the S. aureus in our country, whereas among the S. epidermidis as many as
      half of the blood isolates in central hospitals were multiresistant.

PMID- 8562030
TI  - Significance of variations in section mounting technique for nuclear stereology
      and morphology in urinary bladder neoplasms.
AB  - Owing to its toxicity it would be desirable to avoid xylene in the processing of
      histological tissue. Consequently, modifications of the section mounting
      technique excluding xylene have recently been suggested. Changes in tissue
      preparation might, however, influence histopathological structures used for
      malignancy grading of tumours. In the current study, we investigated the impact
      of alterations in the mounting process on the subjectively evaluated quality of
      nuclear morphology and on the stereologically obtained mean nuclear volume,
      vv(nuc), of urothelial neoplasms. Paraffin sections from 14 tumours were, after
      the haematoxylin-eosin staining, mounted with DPX and a coverslip either, 1) from
      the water bath, 2) after dehydration in ethanol but without clearing, or, 3)
      after dehydration and xylene clearing. We found that the nuclear morphology of
      ethanol-treated and xylene-cleared specimens was somewhat more brilliant than
      that of sections mounted from water. The vv(nuc) of xylene-cleared sections
      ranged from 142 to 751 microns3, and the mean value of 350 microns3 was not
      significantly different from that of ethanol-treated sections of 367 microns3 (2p
      = 0.67). In contrast, the mean vv(nuc) of sections mounted from water was 459
      microns3, approximately 30% larger (2p < or = 0.02). Thus, although previous
      studies have demonstrated the prognostic value of vv(nuc) in patients with
      bladder cancer, the present study shows that modifications in section mounting
      technique may significantly influence the results, underscoring the need for
      standardization of tissue processing. Sections mounted from ethanol seem to be as
      good as routine xylene-cleared sections, whereas sections mounted from water have
      a less brilliant morphology and results of nuclear stereology different from
      those of routine sections.

PMID- 8562031
TI  - Localization of intercellular adhesion molecule-1 in middle ear cholesteatoma.
AB  - Intercellular adhesion molecule-1 (ICAM-1) may have a role in acquired
      cholesteatoma, which is usually associated with an inflammatory reaction
      occurring in the middle ear cavity. The presence of ICAM-1 in human
      cholesteatomas was demonstrated by an immunoblotting assay using a specific
      monoclonal anti-ICAM-1 antibody after protein extraction. Distribution of ICAM-1
      in the cholesteatoma tissues was then studied by avidin-biotin-peroxidase complex
      staining. ICAM-1 appeared to be localized on keratinocytes in all layers of the
      epithelium and on Langerhans cells in both the epithelium and granulation tissue
      of cholesteatoma. ICAM-1 was not found in the epidermis of normal external ear
      canal skin, normal tympanic membrane or normal facial skin, but significant
      staining was seen on keratinocytes of hair follicles and glands in the facial
      skin. The present study is the first to demonstrate ICAM-1 in cholesteatoma and
      suggests that it may have an important role in the clinical development of
      cholesteatoma, including migration, adhesion and proliferation of lymphocytes,
      Langerhans cells and keratinocytes.

PMID- 8562032
TI  - The 6 kHz acoustic dip in school-aged children in Finland.
AB  - In the present study, pure-tone audiometry was used in 687 Finnish school
      children, aged 6-15 years, to determine the prevalence of a 6 kHz acoustic dip
      and related factors among three age groups. Trained audiometricians tested air
      conduction thresholds in a sound-proof room. A total of 57 children (8.3%) had a
      clear-cut dip of at least 20 dB at 6 kHz. This dip was more pronounced in older
      children and in boys. A thorough case history was obtained by questionnaire, with
      logistic regression analysis showing that low birth weight (< 2500 g) and
      childhood measles were the only factors associated with occurrence of the 6 kHz
      dip in school-aged children.

PMID- 8562033
TI  - Aneuploidy in salivary gland adenomas.
AB  - The occurrence of abnormal nuclear DNA content in major salivary gland adenomas
      is not well known and its correlation with tumor recurrence has not been
      documented previously. From 1987 to 1991, 119 consecutive major salivary gland
      adenomas were operated on at Turku University Central Hospital. These tumors were
      analyzed by flow cytometry and 100 (84%) were found to be diploid, 12 (10%) near
      diploid and 7 (6%) aneuploid with DNA indexes > 1.15. The mean proliferation rate
      measured as a percentage of cells in the S-phase fraction was 2.5 +/- 1.6%. The
      histological slides were then blindly reclassified according to current World
      Health Organization classification. As a result histological classification was
      changed in 3 tumors: malignant cells were found in 2 aneuploid tumors and 1
      diploid neoplasm. Preoperative cytological fine-needle aspiration biopsy had been
      considered as possibly malignant in 2 of these cases. Among all case material 10
      specimens were recurrent tumors; although the tendency to recur depended on the
      extent and adequacy of the surgery performed, multiple recurrences were
      associated with non-diploid tumors.

PMID- 8562034
TI  - Preoperative computed tomography in patients requiring a bone-anchored hearing
      aid.
AB  - A preoperative computed tomography technique, "Dentascan" or "Dentatool", was
      used to find the optimal site for implant installation in patients requiring a
      bone-anchored hearing aid. The technique is demonstrated in a patient with
      bilateral bone conduction hearing loss who was treated with bilateral bone
      anchored hearing aids.

PMID- 8562035
TI  - A comparison of the effect of cochlear perfusion with ouabain on summating
      potentials and distortion product otoacoustic emissions in the guinea pig.
AB  - In order to investigate whether or not the summating potential (SP) and the 2f1
      f2 distortion product otoacoustic emission (DPOAE) are due to related cochlear
      non-linearities, their behavior was studied in the guinea pig after intracochlear
      perfusion with ouabain and subsequent rinsing. The SP was evoked with either 4 or
      8 kHz tone bursts, and the 2f1-f2 DPOAE was evoked with simultaneous
      presentations of 6.6 and 8 kHz continuous tones. After ouabain perfusion, DPOAE
      was dramatically reduced while the SP underwent only a small reduction. After
      rinsing out the ouabain with artificial perilymph, the DPOAE showed partial
      recovery while the SP displayed a large and long-lasting increase when compared
      to its a initial value. These results suggest that the non-linear processes
      giving rise to the SP and DPOAE are not identical.

PMID- 8562037
TI  - DNA amplification for the in vitro detection of Candida albicans in head and neck
      squamous cell carcinomas.
AB  - DNA was extracted from whole cells of Candida albicans and digested with HindIII
      restriction enzyme. After electrophoresis in a segment of the lane containing
      between 800 and 1200 base pairs (bp) of DNA fragments, a 1.1-kilobase (kb)
      fragment was found that hybridizes to biopsied tumor cells from head and neck
      squamous cell carcinomas (SCC). From the nucleotide sequence of the putative gene
      locus, primers were synthesized for use in a polymerase chain reaction (PCR) with
      DNA extracted from 18 SCC of the upper aerodigestive tract. After 30 cycles of
      amplification all tumors were found to contain sufficient amplified DNA to be
      detected in polyacrylamide or agarose gels. In contrast, template DNA from lymph
      nodes and malignant lymphomas failed to generate positive signals under these
      conditions. However, samples of DNA obtained from head and neck SCC cells in
      vitro, Candida glabrata, and Candida parapsilosis after PCR were found to contain
      homologous sequences. Application of this technique to head and neck SCC biopsies
      may help to identify quickly the presence of concurrent candidal species.

PMID- 8562036
TI  - In vivo effects of thymostimulin treatment on monocyte polarization, dendritic
      cell clustering and serum p15E-like trans-membrane factors in operable head and
      neck squamous cell carcinoma patients.
AB  - Head and neck squamous cell carcinoma patients have been characterized by
      impairments in their cell-mediated immune system, particularly by decreased
      chemotactic function of monocytes and impairments in the function of the monocyte
      derived dendritic cells (viz, a decreased capability to form cell "clusters").
      These impairments are thought to be due to immunosuppressive factors of low
      molecular mass released by tumor, the so-called p15E-like factors. These
      suppressive effects of p15-like factors can be neutralized in vitro by thymic
      peptides, such as thymostimulin (TP1). In a randomized double-blind, placebo
      controlled multicenter trial in the Netherlands, 41 patients with operable head
      and neck squamous cell carcinomas (HNSCC) were treated for 10 days prior to
      surgery with intramuscular TP1 in one of three dosages (0.5 mg/kg; 1.0 mg/kg or
      2.0 mg/kg body weight) or treated with placebo. Assessment of monocyte
      chemotaxis, the capability of dendritic cells to form clusters and the presence
      of p15E-like low-molecular-mass factors (LMMFs) in serum was performed before TP1
      treatment and on the day of surgery. Findings demonstrated that TP1 in a dose of
      1.0 mg/kg and 2.0 mg/kg resulted in normalization of impaired monocyte
      chemotactic capability. Although the cluster capability of dendritic cells after
      TP1 treatment improved, values only reached statistical significance for the 0.5
      mg/kg group. Serum p15E-like LMMF levels were not affected by TP1 treatment in
      any of the patient groups. Contrary to expectations we found no correlation
      between elevated immunosuppressive LMMFs and defective monocyte chemotaxis or
      cluster capability of dendritic cells. We conclude that treatment with TP1 can
      improve monocyte chemotaxis in HNSCC patients but an effect on the production of
      p15E-like factors by carcinoma cells could not be demonstrated.

PMID- 8562038
TI  - Experimental studies on the suitability of the erbium laser for stapedotomy in an
      animal model.
AB  - Animal experiments in mature guinea pigs were devised to determine whether and to
      what extent inner ear damage can be caused by in vivo use of the erbium laser for
      stapedotomy. The present study examined the laser effect in connection with
      perforation of the basal convolution of the cochlea and subsequent application in
      the opened cochlea. Acoustic evoked potentials as compound action potentials
      (CAP) were recorded for changes in inner ear function. Findings demonstrated that
      five applications of the erbium:YSGG (yttrium-scandium-gallium-garnet) laser
      (energy, 85 mJ/pulse; energy density, 36 J/cm2) were needed to create a footplate
      perforation of 500-600 microns and did not lead to CAP alteration in any animal
      (n = 20). An increase of the repetition rate from 1 to 5 Hz likewise caused no
      CAP alteration (n = 17). Application of high total energies in the open cochlea
      (n = 5) to determine the safety of the laser system for stapedotomy revealed that
      a 10-fold increase in the total energy required for adequate perforation led to
      irreversible CAP alterations and no CAP could be recorded at a 15-fold increase
      in total energy. In contrast, a 5-fold maximum increase in total energy caused no
      CAP alterations. These results demonstrate the safety of the Er:YSGG laser
      comparable to that of the CO2 laser for stapedotomy, supporting its utility as an
      alternative method for surgery.

PMID- 8562039
TI  - The role of middle ear effusions and epidermal growth factor in cholesteatoma
      formation in the gerbilline temporal bone.
AB  - To study the process of aural cholesteatoma formation, we used gerbilline
      temporal bones to examine histologically the early stages of spontaneous
      cholesteatomas associated with experimentally induced otitis media with effusion
      (OME) following electric cauterizations of the eustachian tube. Epidermal growth
      factor (EGF) was then localized immunohistochemically in the pars flaccida of
      normal ears and the forming spontaneous cholesteatomas. Findings in the ears with
      the early spontaneous cholesteatomas were effusion inside the pars flaccida and
      hypertrophy and hyperkeratosis of the pars flaccida. Findings in the ears with
      experimental OME involved an effusion in the whole middle ear cavity as well as
      hypertrophy and hyperkeratosis in both the pars flaccida and pars tensa. The
      incidence of ear drum changes was higher in the experimental OME group than in
      control animals without cauterization. EGF was localized in the mucous layer of
      normal drums, the mucous layer and lamina propria of drums with hypertrophy
      alone, and all layers in drums with hypertrophy and hyperkeratosis. EGF was
      especially positive in the cytoplasms of transformed cuboidal cells. These
      findings suggest that EGF within the transformed mucous layer may play an
      important role as a biochemical factor in developing cholesteatomas.

PMID- 8562040
TI  - Dose-dependent access of murine anti-epidermal growth factor receptor monoclonal
      antibody to tumor cells in patients with advanced laryngeal and hypopharyngeal
      carcinoma.
AB  - The murine IgG2a monoclonal antibody (mAb) EMD 55900 was produced against the
      human epidermoid carcinoma cell line A431, with binding occurring to the
      polypeptide chain of the external domain of human epidermal growth factor
      receptor (EGF-R). In the present clinical study, 12 patients with advanced
      squamous cell carcinoma of the larynx or hypopharynx received a single dose of
      either 20, 100 or 400 mg EMD 55900 3 days prior to laryngectomy and neck
      dissection. Clinical signs and laboratory parameters of toxicity, development of
      human anti-mouse antibodies, and mAb plasma concentrations were monitored. In
      tumor specimens studied from primary tumors and lymph node metastases, expression
      of EGF-R, distribution of EMD 55900, and occupation of EGF-R by EMD 55900 (double
      staining) were determined by immunohistochemistry. Single-dose administration of
      EMD 55900 was very well tolerated in all patients, and good (100 mg) to excellent
      (400 mg) homogeneous binding of mAb to EGF-R was obtained in the advanced
      laryngeal and hypopharyngeal carcinomas studied.

PMID- 8562041
TI  - Asymptomatic carotid artery occlusion from a gunshot. The role of angiography in
      penetrating neck trauma.
AB  - Recognition of a carotid artery injury after a gunshot neck wound can be
      difficult to make in the absence of physical signs. Currently, the usefulness of
      preoperative angiography in detecting penetrating neck trauma is controversial.
      We present a case of an angiography proven asymptomatic carotid artery occlusion
      after a gunshot. Indications for angiography after neck trauma are discussed.

PMID- 8562042
TI  - Collagen types in the middle ear mucosa.
AB  - The distribution of various collagen types--in particular that of type II as the
      major collagen in cartilage--in normal auricular structures is discussed with
      reference to a 1994 report by Ovesen describing the presence of collagen type II
      in normal middle ear mucosa. In contrast to this report, no collagen type II is
      normally found in the normal mucosa of the middle ear, while multiple structures
      of the normal middle and inner ear (which mostly consist of cartilage or have at
      least a cartilaginous origin) contain this unique collagen type. This indicates
      that the collagen type II staining previously observed in the normal middle ear
      mucosa is most likely an artifact. Of the at least 18 collagen types now known,
      interstitial and ubiquitously present types I, III and V can be found in the
      normal middle ear. The minor cartilage collagen types IX and XI have been found
      in cartilage of the middle (and inner) ear. The basement membrane collagen type
      IV is normally present in different microanatomical settings, particularly in the
      epithelial and endothelial basement membranes. In general, an exclusive
      morphometric estimation of area changes for collagens, particularly for collagen
      type IV, regardless of any tissue localization seems to be of minor value, since
      no attribution can be drawn to any of the histoanatomical structures present in
      the ear. The presence of further collagen types has not yet been tested in normal
      auricular structures.

PMID- 8562043
TI  - Developmental control of transcription of the CAT reporter gene by a truncated
      mouse alphafetoprotein gene regulatory region in transgenic mice.
AB  - A truncated mouse alphafetoprotein (AFP) gene promoter/enhancer region was tested
      for its ability to regulate the expression of the Escherichia coli
      chloramphenicol acetyltransferase (CAT) reporter gene in the livers of transgenic
      mice. The AFP regulatory region lacked any AFP gene structural DNA, included one
      enhancer sequence together with the proximal promoter sequence, and an element
      believed to be responsible for the postnatal repression of AFP gene
      transcription. The neonatal livers of AFP/CAT transgenic mice showed a high level
      of CAT enzyme expression, which was dramatically reduced between 7 and 14 days
      after birth. The staining of liver sections with anti-CAT antibodies showed that
      this expression was limited to hepatocytes. In one lineage, reexpression of CAT
      in the adult liver could be achieved by restitutive proliferation of hepatocytes
      following partial hepatectomy or CCl4-induced necrosis; reexpression in young
      animals (3-4 weeks of age) was even greater. These studies show that a truncated
      AFP promoter/enhancer region functions in a tissue-specific and developmental
      stage-specific fashion, and may be used to control the expression of other genes
      in the livers of transgenic mice.

PMID- 8562044
TI  - Formation of the sea urchin male pronucleus in vitro: membrane-independent
      chromatin decondensation and nuclear envelope-dependent nuclear swelling.
AB  - We demonstrate that complete sea urchin male pronuclear development in vitro is a
      two-step process involving membrane-independent chromatin decondensation and
      nuclear envelope-dependent pronuclear swelling. In the absence of cytoplasmic
      membrane vesicles (MVs), permeabilized sperm chromatin decondenses into a
      spherical nucleus of approximately 4 microns in diameter. Pronuclear swelling to
      approximately 7 microns requires an intact nuclear envelope, and the degree of
      swelling is limited by the amount of MVs assembled on the chromatin. Furthermore,
      after a nuclear envelope is formed, swelling can occur in the absence of
      additional cytoplasmic MVs. Nuclear swelling also requires ATP hydrolysis, Ca2+
      and cytosolic factors, some of which are sensitive to heat and to the sulfhydryl
      alkylating agent, N-ethylmaleimide. The requirement for a nuclear envelope and
      the rate of pronuclear swelling are consistent with previous in vivo
      observations.

PMID- 8562045
TI  - Effects of different kinases and phosphatases on nuclear and cytoplasmic
      maturation of bovine oocytes.
AB  - Phosphorylation is considered as a common post-translational modification
      implicated in the control of various key enzymes. In somatic and germinal cells,
      important regulators of the cell cycle are controlled by their phosphorylation
      status, and some act as kinases or phosphatases themselves. Bovine oocytes are
      blocked in the germinal vesicle (GV) stage until either an LH surge occurs or
      until oocytes are released from the inhibitory influence of the follicle. Meiotic
      resumption in vitro is therefore an excellent model for the study of
      phosphorylation events that occur in the G2/M transition, a control point of the
      cellular cycle. To better understand this transition, we have modulated, either
      directly or indirectly, kinases using known effectors (epidermal growth factor,
      EGF; isobutylmethylxanthine-forskolin, Bx-Fk; 6-dimethylaminopurine, 6-DMAP) or
      phosphatases (okadaic acid, OA) or cycloheximide, which is known to inhibit
      maturation through protein synthesis suppression. With this procedure, influence
      on meiotic resumption and phosphoprotein patterns was verified. Both EGF and OA
      accelerated nuclear maturation after 9 hr of culture. Only 23% (n = 140) and 9%
      (n = 111) of oocytes were still at GV stage with EGF and OA, respectively,
      compared to 41% (n = 105) of control oocytes. The different treatments changed
      the protein patterns in oocytes. In cumulus cells, the patterns were especially
      modified by the OA treatment. Characteristic changes that occur in germ cells
      were also identified. Nuclear maturation was inhibited by modulators of kinase (6
      DMAP, GV = 74%, n = 126; cAMP dependent protein kinase (PKA) stimulators, Bx-Fk,
      GV = 71%, n = 129) likewise, phosphoprotein patterns were affected, especially in
      oocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562046
TI  - Low temperature and fertilization-induced Ca2+ changes in rat eggs.
AB  - In mammalian eggs, activation by sperm that leads to resumption of meiosis is
      characterized by an explosive transient increase in intracellular calcium ion
      concentration ([Ca2+]i), followed by [Ca2+]i oscillations. In addition to the
      spermatozoon, various treatments can induce parthenogenetic activation,
      accompanied by an elevation of [Ca2+]i. It has been reported that cooling can
      induce egg activation, yet the mechanism of this phenomenon has not been
      elucidated. In the present study we followed changes in egg [Ca2+]i (measured by
      Fura-2 fluorescence ratio imaging) during activation by cooling, using conditions
      that ensure a low rate of spontaneous activation. Our present findings
      demonstrate that cooling induces egg activation as manifested by [Ca2+]i
      transient(s) and second polar body extrusion. Seventy-eight of 104 eggs responded
      to cooling with increased [Ca2+]i. Thirty-five percent of the responding eggs
      displayed a single [Ca2+]i transient, while 65% exhibited at least two [Ca2+]i
      transients within the time window of the experiment (30-40 min). Twenty-two
      percent of these eggs displayed high-frequency oscillations (intervals of 3.5-5.9
      min). In these eggs, the overall pattern of calcium dynamics was similar to that
      observed in eggs activated by sperm, as judged by the transient's intervals,
      duration, and a gradual increase in the amplitude of successive transients. The
      amplitudes of [Ca2+]i transients, however, were 2-3 times lower. We propose that
      cooling affects [Ca2+]i homeostasis to produce fertilization-like changes in
      [Ca2+]i, possibly associated with parthenogenetic activation. Moreover, great
      care should be exercised to prevent temperature changes during egg handling.

PMID- 8562047
TI  - Differential gene expression during early murine yolk sac development.
AB  - The visceral yolk sac (VYS), composed of extraembryonic mesoderm and visceral
      endoderm, is the initial site of blood cell development and serves important
      nutritive and absorptive functions. In the mouse, the visceral endoderm becomes a
      morphologically distinct tissue at the time of implantation (E4.5), while the
      extraembryonic mesoderm arises during gastrulation (E6.5-8.5). To isolate genes
      differentially expressed in the developing yolk sac, polymerase chain reaction
      (PCR) methods were used to construct cDNA from late primitive streak to neural
      plate stage (E7.5) murine VYS mesoderm and VYS endoderm tissues. Differential
      screening led to the identification of six VYS mesoderm-enriched clones:
      ribosomal protein L13a, the heat shock proteins hsc 70 and hsp 86, guanine
      nucleotide binding protein-related gene, cellular nucleic acid binding protein,
      and alpha-enolase. One VYS endoderm-specific cDNA was identified as
      apolipoprotein C2. In situ hybridization studies confirmed the differential
      expression of these genes in E7.5 yolk sac tissues. These results indicate that
      representative cDNA populations can be obtained from small numbers of cells and
      that PCR methodologies permit the study of gene expression during early mammalian
      postimplantation development. While all of the mesoderm-enriched genes were
      ubiquitously expressed in the embryo proper, apolipoprotein C2 expression was
      confined to the visceral endoderm. These results are consistent with the
      hypothesis that at E7.5, the yolk sac endoderm provides differentiated liver-like
      functions, while the newly developing extraembryonic mesoderm is still a largely
      undifferentiated tissue.

PMID- 8562048
TI  - Transcription and localization of growth factor mRNA in the bovine oviduct.
AB  - It has become evident that certain growth factors are involved in the regulation
      of the initial bovine embryogenesis. In the present study, we examined by means
      of Northern blot and in situ hybridization, the expression and localization in
      the bovine oviduct of mRNAs encoding for platelet-derived growth factor (PDGF-B),
      basic fibroblast growth factor (bFGF), and insulin-like growth factor (IGF-I).
      Northern blot analysis on oviduct tissue demonstrated transcripts for PDGF-B and
      bFGF, but not IGF-I mRNAs. Two bands with estimated sizes of 5.0 and 1.5 kb were
      detected for PDGF-B and two bands with sizes of 7.5 and 4.9 kb for bFGF. In situ
      hybridization analysis demonstrated localization of PDGF-B mRNA in the lamina
      epithelialis and tunica muscularis of the oviduct whereas bFGF mRNA was detected
      in the lamina propria. It is concluded that the lamina epithelialis and lamina
      propria of the oviduct represent sites of synthesis of PDGF-B and bFGF mRNA,
      respectively.

PMID- 8562049
TI  - In vitro pluripotency of epiblasts derived from bovine blastocysts.
AB  - Two experiments were conducted to compare the utility of in vitro- and in vivo
      derived bovine blastocysts for the isolation of pluripotent epiblasts. In
      experiment 1, the inner cell masses (ICMs) of in vivo-collected blastocysts
      yielded a higher proportion of epiblasts after culture on STO feeder cells than
      ICMs from in vitro-produced blastocysts (P = .0157). In experiment 2, ICMs of in
      vivo-collected blastocysts that hatched on day 8 yielded a greater proportion of
      epiblasts after culture on STO feeder cells than ICMs from in vitro-produced
      blastocysts that hatched on day 8. The difference was reversed but smaller for
      blastocysts that hatched on day 9 (Interaction, P = .0125). Epiblasts from
      blastocysts that hatched on day 8 regardless of their source generated more
      differentiated cell lines in extended culture than did blastocysts that hatched
      on day 9. Extended epiblast culture yielded cells identifiable as products of the
      three embryonic germ layers that included epithelial cells, fibroblasts, neuronal
      cells, hepatocyte-like cells, and macrophage-like cells. Alkaline phosphatase
      activity combined with cell morphology identified the bovine epiblast cells and
      distinguished them from trophectoderm and endoderm that frequently contaminated
      epiblast cell cultures. In vivo-derived blastocysts, especially from early
      hatching blastocysts, were a superior source of pluripotent epiblasts. Epiblast
      cells in this study all differentiated or senesced indicating that standard
      conditions for mouse embryonic stem cell culture do not maintain bovine epiblast
      cells in an undifferentiated state.

PMID- 8562050
TI  - Effect of donor embryo cell number and cell size on the efficiency of bovine
      embryo cloning.
AB  - To establish reliable criteria for the evaluation of nuclear donor embryos, we
      studied the effect of cell number and cell size of in vitro produced day 6 donor
      morulae on the rate of blastocyst formation following nuclear transfer to in
      vitro matured oocytes. In experiment 1, donor embryos were divided into three
      groups with low (25-34), intermediate (40-55), and high (60-81) blastomere
      numbers. Transfer of nuclei from day 6 morulae with intermediate and high cell
      numbers resulted in a significantly higher blastocyst rate (31% and 32%,
      respectively) than use of nuclei from day 6 morulae with low cell numbers (17%)
      or nuclei from day 7 morulae with 50-83 blastomeres (19%). This suggests that
      blastomeres from the developmentally advanced day 6 morulae are more viable than
      blastomeres from retarded embryos. In experiment 2, we evaluated the effect of
      blastomere size in day 6 donor morulae with intermediate (40-55) or high (60-81)
      cell numbers on the efficiency of nuclear transfer. In both classes of embryos,
      small blastomeres were better nuclear donors than large blastomeres. The rates of
      development to the blastocyst stage were 28% versus 15% (40-55 cells) and 41%
      versus 25% (60-81 cells), suggesting that small blastomeres include a higher
      proportion of totipotent cells than the polarized large blastomeres. Our results
      demonstrate that blastomere number and size markedly affect the efficiency of
      nuclear transfer and therefore are useful criteria for evaluating nuclear donor
      embryos. These parameters are easy to determine and may therefore be helpful to
      improve the efficiency of cattle cloning.

PMID- 8562051
TI  - Ultrastructure of the spermatozoa and eggs of the ocean pout (Macrozoarces
      americanus L.), an internally fertilizing marine fish.
AB  - Ultrastructure of sperm and eggs of the ocean pout (Macrozoarces americanus L.),
      an internally fertilizing marine teleost, was examined by scanning and
      transmission electron microscopy. The results showed that the sperm do not have
      an acrosome but have a very long mid-piece (one to two times the sperm head
      length) containing numerous well-developed elongated mitochondria. The sperm also
      have two tails (is biflagellate) each consisting of nine peripheral and one
      central pair (9 +/- 2) of microtubules. This long mid-piece and the biflagellate
      nature of the sperm appear to be associated with the long life-span of the sperm
      and with sperm dispersal in the ovary to fertilize the eggs internally. The ocean
      pout eggs are enveloped by a porous chorionic membrane similar to that found in
      other teleosts but have two micropyles, a condition likely related to a mechanism
      of egg fertilization which increases the egg fertility in the presence of low
      sperm numbers. Following insemination, some biochemically undefined excretions
      appeared on the surface of fertilized eggs and led to the acquisition of adherent
      capability of the eggs which formed a tightly associated egg mass in sea water.

PMID- 8562052
TI  - Stimulation of bovine sperm motility and respiration by the triazine dye cibacron
      blue F3GA.
AB  - Bovine sperm motility and respiration were stimulated by the triazine dye
      Cibacron Blue F3GA (CB), which may operate as a nucleotide mimic. CB stimulation
      of respiration was half-maximal at about 35 microM and respiration reached
      maximal levels about 1.5 minutes after CB addition. Respiratory stimulation was
      preceded by a transient increase in cytosolic cAMP. Sperm cAMP titers were
      elevated from 5 to 10 pmoles/10(8) cells within 30 seconds of CB addition, but
      rapidly dropped to a stable level of about 7.5 pmoles/10(8) cells. CB was a
      potent inhibitor of sperm membrane adenylyl cyclase and inhibited respiration in
      permeabilized cells. Taken together, the data indicated that CB stimulation was
      not manifested via the cytosol. In addition, a nonpermeant blue dextran
      preparation synthesized with CB also stimulated sperm respiration and motility.
      CB inhibited sperm membrane phosphodiesterase activity, suggesting that the
      transient pulse of cAMP resulted from CB interaction with this enzyme in the
      sperm membrane.

PMID- 8562053
TI  - Molecular cloning, tissue distribution, and hormonal control in the ovary of Cx41
      mRNA, a novel Xenopus connexin gene transcript.
AB  - Gap junctions (GJ) are aggregates of intercellular channels, composed of connexin
      (Cx) protein, between adjacent cells. The vertebrate ovarian follicle contains
      homocellular (granulosa cell-granulosa cell) and heterocellular (granulosa cell
      oocyte) GJ. However, the function of GJ during final oocyte differentiation
      (maturation) is controversial. The objectives of this study are to reexamine the
      number and identity of Cx genes that are expressed in the Xenopus ovary, and to
      examine the potential role of GJ in oocyte maturation by determining the temporal
      association between changes in ovarian Cx mRNA content and the process of
      maturation. We used reverse transcriptase-polymerase chain reaction to amplify
      ovarian cDNA fragments using degenerate Cx primers. We amplified three Cx-like
      fragments: one was novel and two corresponded to known Cx of Xenopus ovaries
      (Cx38 and 43). The novel fragment was used to screen an ovarian cDNA library. One
      positive clone was identified and its nucleotide sequence determined. Its deduced
      amino acid sequence showed that it corresponded to a novel Cx, Cx41, belonging to
      the Group II class of Cx. Xenopus Cx41 showed the highest homology to rat Cx37
      (65% identity, 80% similarity). Also, the last 10 C-terminal amino acids of Cx41
      were identical to those of rat, mouse, and human Cx37. Cx41 transcripts were
      detected by riboprobe mapping in ovarian somatic cells, heart, leg muscle, liver
      and eye, but not in brain or in oocytes of any developmental stage. Full-grown
      follicles incubated in vitro with human chorionic gonadotropin became committed
      to mature within 1-4 hr, and physical signs of maturation (germinal vesicle
      breakdown) were seen at 4-5 hr. Significant reductions in the levels of Cx41 and
      43, but not 38 transcripts were seen at 4 hr, after oocytes had committed to
      mature. Thus, if availability of Cx mRNA determines availability of Cx protein
      and GJ, our results would suggest that irreversible commitment to maturation
      occurred prior to major declines in follicular GJ during the periovulatory
      period. The present study is the first to report the presence of at least two
      hormone-responsive Cx gene transcripts (Cx41 and 43 in Xenopus) in ovaries of a
      single animal species.

PMID- 8562054
TI  - Intra-acrosomal 155,000 dalton protein increases the antigenicity during mouse
      sperm maturation in the epididymis: a study using a monoclonal antibody MC101.
AB  - We found an intra-acrosomal antigen of about 155,000 daltons (155 kDa) in a
      survey using the monoclonal antibody MC101 raised against mouse cauda epididymal
      spermatozoa. Morphological studies by means of indirect immunofluorescence and
      immunogold electron microscopy localized the antigen to the cortex region of the
      anterior acrosome. Avidin biotin complex immunocytochemistry initially
      demonstrated a faint signal at the anterior acrosome in the testis spermatozoa
      that increased in intensity as the sperm moved toward the distal epididymis. This
      incremental immunoreactivity was also confirmed by immunoblotting following one
      dimensional SDS-PAGE. The 155 kDa protein band was immunostained, and it was much
      more intense in the cauda epididymal than in the caput and corpus epididymal
      spermatozoa. Only a trace or no immunostain was evident in the caput or testis
      spermatozoa. The antigen localization did not change during passage through the
      epididymis, being confined at the cortex region of the anterior acrosome. The
      epididymal epithelial cells were not immunostained. These findings suggested that
      the 155 kDa protein is biochemically modified, further implying that the
      biochemical alteration of intra-acrosomal material is involved in sperm
      maturation in the epididymis.

PMID- 8562055
TI  - Further indications of the multicomponent nature of the acrosome reaction
      inducing substance of human follicular fluid.
AB  - Human follicular fluid (hFF), which has been treated with either unspecific
      proteases or dextran-coated charcoal (DCC) to remove proteins and/or steroids,
      cannot successfully induce the acrosome reaction (AR). After the removal of
      steroids, AR-inducing activity can be restored to hFF by supplementation with
      exogenous progesterone, but only in the presence of intact protein. Gel
      filtration experiments with 3H-progesterone-labelled hFF showed elution of the
      radioactive signal in the high molecular weight range, corresponding to bound
      progesterone. AR-inducing activity was seen in exactly the same fraction. Based
      on these results, the acrosome reaction-inducing substance (ARIS) appears to be a
      complex of progesterone and a progesterone-binding protein, which was shown to be
      identical with the plasma protein corticosteroid-binding globulin (CBG) by
      immunological techniques. AR induction was only observed in the presence of both
      CBG and progesterone, suggesting a combined effect of the two components.

PMID- 8562056
TI  - Reliability of aneuploidy estimates in human sperm: results of fluorescence in
      situ hybridization studies using two different scoring criteria.
AB  - Aneuploidy estimates for chromosomes 1, 12, X, and Y were obtained in human sperm
      from five donors using multicolor fluorescence in situ hybridization (FISH)
      analysis. Disomy frequencies were obtained by scoring a minimum of 10,000 sperm
      for each chromosome probe per donor. This analysis was replicated for two scoring
      criteria: one used one half of a signal domain as the minimum distance between
      two signals to be counted as two and thus disomic; the other set one signal
      domain as the minimum distance between two signals. A total of 120,870 sperm were
      assessed using one half of a domain as the criterion, and 113,478 were scored
      using one domain as the criterion. The percentage of disomy for chromosomes 1,
      12, X, Y, and XY was 0.18, 0.16, 0.15, 0.19, and 0.25, respectively, using the
      one-half-domain criterion, and 0.08, 0.17, 0.07, 0.12, and 0.16, respectively,
      using the one-domain criterion. The percentage of disomy decreased significantly
      with use of one domain as the minimum distance for signal separation for all
      chromosomes except for chromosome number 12. These lower disomy frequencies
      correlated well with frequencies derived from human sperm karyotypes analyzed in
      our laboratory. This suggests that the fluorescent signals for chromosomes 1, X,
      and Y split into more than one domain in decondensed interphase sperm, and that
      the use of the one-half-domain criterion would lead to an overestimate of
      aneuploidy frequencies. The factors known to affect aneuploidy estimates derived
      from FISH studies are discussed, and recommendations for stringent scoring
      criteria are proposed.

PMID- 8562057
TI  - Structural and endocrine aspects of equine oocyte maturation in vivo.
AB  - The objectives were to describe the ultrastructure of equine oocytes aspirated
      from small and preovulatory follicles, and to relate the ultrastructural features
      to follicle size and follicular fluid steroid concentrations. Mares were examined
      every second day by transrectal ultrasonography, and follicles measuring > 30 mm
      were aspirated (in vivo) using a 20-cm-long 12-gauge needle through the flank.
      Following slaughter, both large and small follicles were aspirated (in vitro)
      from six mares. The oocytes were isolated under a stereomicroscope and processed
      for transmission electron microscopy, and the follicular fluid was assayed for
      progesterone (P4) amd estradiol-17 beta (E2). A total of 29 oocytes (32% recovery
      rate) were aspirated in vivo, and 15 oocytes were recovered in vitro. According
      to the stage of nuclear maturation, the oocytes could be divided into the
      following six categories: 1) the central oocyte nucleus (CON) stage, 2) the
      peripheral spherical oocyte nucleus (PON-I) stage, 3) the peripheral flattened
      oocyte nucleus (PON-II) stage, 4) the oocyte nucleus breakdown (ONBD) stage, 5)
      the metaphase I (M-I) stage, and 6) the metaphase II (M-II) stage. The maturation
      of the preovulatory follicle was reflected by alterations in the follicular fluid
      concentrations of steroid hormones. E2 was high in all preovulatory follicles,
      whereas P4 concentration exhibited a 10-fold increase during follicle maturation,
      particularly associated with the progression from M-I- to M-II-stage oocytes. The
      nuclear oocyte maturation included flattening of the spherical oocyte nucleus,
      followed by increasing undulation of the nuclear envelope, formation of the
      metaphase plate of the first meiotic division, and, finally, the extrusion of the
      first polar body and the subsequent formation of the metaphase plate of the
      second meiotic division. The cytoplasmic oocyte maturation changes comprised
      breakdown of the intermediate junctions between the cumulus cell projections and
      the oolemma, enlargement of the perivitelline space, the formation and
      arrangement of a large number of cortical granules immediately beneath the
      oolemma, the rearrangement of mitochondria from a predominantly peripheral
      distribution to a more central or semilunar domain, and the rearrangement of
      membrane-bound vesicles and lipid droplets from an even distribution to an often
      semilunar domain, giving the ooplasm a polarized appearance. It is concluded that
      the final equine oocyte maturation includes a series of well-defined nuclear and
      cytoplasmic changes that are paralleled by an increase in P4 concentration in the
      follicular fluid, whereas E2 concentration remains constantly high.

PMID- 8562058
TI  - Transforming growth factor beta 1 expression in the endometrium of the mare
      during placentation.
AB  - In situ hybridization, Northern blotting, and immunohistochemical techniques were
      used to study the expression of transforming growth factor beta 1 (TGF beta 1) in
      the endometrium of the mare during the first 150 days of pregnancy (term = 330
      340 days). In situ hybridization using an oligonucleotide (45mer) probe, based on
      a homologous region within all known mammalian TGF beta 1 DNA sequences,
      demonstrated TGF beta 1 mRNA accumulation in the glandular and lumenal epithelial
      cells of the endometrium from day 33 onwards which corresponds to the time of
      implantation (day 33-45). Expression in the endometrium remained at a high level
      to the end of the sampling period (day 150). There was also marked expression of
      TGF beta 1 in the mononuclear cells accumulated around the periphery of the
      specialized trophoblast cells of the endometrial cup within the endometrium and
      in the mononuclear cells accumulated in the endometrial stroma of mares carrying
      failing donkey-in-horse pregnancies created by embryo transfer. The sense
      (control) oligonucleotide probe exhibited no hybridization to any tissue at any
      stage. Northern blot analysis demonstrated that the oligonucleotide probe and a
      porcine TGF beta 1 cDNA clone hybridized to a single 2.5 kb transcript in horse
      endometrial and lymphocyte RNA, thus validating the oligonucleotide probe for
      detection of horse TGF beta 1 mRNA. Furthermore, both probes demonstrated an
      increased signal in the pregnant endometrium from day 33 onwards, thereby
      confirming the in situ hybridization results. Immunostaining with a specific anti
      bovine TGF beta 1 serum also showed increasing TGF beta 1 accumulation in
      endometrial epithelia during pregnancy, and localization of the protein in
      endometrial stroma and in the trophoblast layer of the placenta after day 60 of
      pregnancy. These results show that TGF beta 1 expression increases in the
      maternal endometrium of the mare at the time of implantation and that it may play
      a role in regulating endometrial and/or trophoblast growth and differentiation
      during placentation in this species. It may also influence fetal development (via
      placental transfer) at a later stage of gestation.

PMID- 8562059
TI  - Cloning of complementary DNA encoding a 135-kilodalton protein secreted from
      porcine corpus epididymis and its identification as an epididymis-specific alpha
      mannosidase.
AB  - In the preceding study (Okamura et al., 1992; Biol Reprod 47:1040-1052) we
      suggested that a 135-kDa protein secreted by porcine epididymis is involved in
      the sperm maturation. In this work, we have isolated the cDNA clone coding the
      135-kDa protein in an effort to investigate its structure and function. The 135
      kDa protein was purified from porcine cauda epididymal fluid. Three
      oligonucleotide probes were synthesized according to the amino acid sequences of
      N-termini of the native protein and trypsin-digested peptides. A cDNA clone
      hybridizing with these three probes was isolated from the cDNA library derived
      from the porcine proximal corpus epididymis. It encodes a novel protein with
      1,006 amino acid residues in an open reading frame. Its overall amino acid
      sequence was significantly homologous (25.7%) to the alpha-mannosidase precursor
      of Dictiostelium discoideum (P34098). The 135-kDa protein could digest both p
      nitro-phenyl-alpha-D-mannoside and high mannose oligo saccharide (Man8-GlcNAc2),
      strongly suggesting that it is an alpha-mannosidase homologue. The expression of
      this protein was specific to porcine and was localized to the very narrow parts
      of epididymis: the border of the caput and corpus epididymis. This protein may
      serve as a good marker for the functional differentiation in porcine epididymis.
      A possible role of this protein in the species-specific sperm-egg interaction is
      discussed.

PMID- 8562060
TI  - Expression of prostatic secretory protein (PSP)-like protein in porcine corpus
      luteum: isolation and characterization of a new gene encoding PSP94-like protein.
AB  - cDNA clones encoding stage-and/or space-specific genes in porcine ovarian
      follicles have been investigated by differential screening of cDNA libraries of
      granulosa cells and corpus luteum. A clone corresponding to mRNA preferentially
      expressed in the functional stage of corpus luteum was found to encode a protein
      similar to the human prostatic secretory protein, PSP94, which had been
      originally identified in male genital organs. The expression was detected widely
      in the functional corpora lutea by in situ hybridization histochemistry, but the
      signal was most prominent in the luteal cells surrounding blood vessels. In
      contrast, despite the structural similarity in their products, the expression of
      this newly identified gene was not detected in porcine prostate, suggesting that
      these structurally related proteins play different roles in mammalian genital
      organs.

PMID- 8562061
TI  - Mouse androgen-dependent epididymal glycoprotein CRISP-1 (DE/AEG): isolation,
      biochemical characterization, and expression in recombinant form.
AB  - In the rat, the secretory glycoprotein DE/AEG is one of the main constituents of
      the epididymal fluid. We have recently reported the cloning of the cDNA for the
      related cysteine-rich secretory protein-1 (CRISP-1) from murine epididymis
      (Haendler et al., 1993; Endocrinology 133:192-198). The protein has now been
      isolated from the same organ and its N-terminal amino acid sequence has been
      determined. CRISP-1 exhibited an isoelectric point of approximately 6.8. High
      levels of CRISP-1 antigen were detected in the corpus and cauda of the
      epididymis, vas deferens, seminal vesicle, prostate, and in the salivary gland by
      immunohistochemistry. A quantitative analysis of the cauda epididymal fluid by
      sandwich ELISA revealed that CRISP-1 represented approximately 15% of the total
      protein. For heterologous expression, the CRISP-1 coding sequence was introduced
      into the pMPSV/CMV vector before transfection of baby hamster kidney (BHK) cells
      and selection with puromycin and neomycin. Expression in insect cells was
      achieved by co-transfection of Sf9 cells with a transfer vector and baculovirus
      DNA. Recombinant CRISP-1 was isolated in quantities sufficient for structural
      analysis. Ethyl maleimide treatment showed that all 16 cysteines were engaged in
      disulfide bonds. Proteolytic digestion demonstrated that the six cysteines
      localized in the N-terminal moiety formed three bonds with each other, suggesting
      the existence of two discrete domains in the protein.

PMID- 8562062
TI  - Mouse embryonic stem cells express receptors of the insulin family of growth
      factors.
AB  - Insulin and insulin-like growth factors (IGF-I and -II) are members of a family
      of growth factors which are known to be developmentally regulated during
      preimplantation mouse embryogenesis. The physiological actions of the insulin
      family of growth factors are mediated by interactions with specific cell surface
      receptors that are detectable on the cells of preimplantation mouse embryos.
      Mouse embryonic stem (ES) cells are totipotent cells derived directly from the
      inner cell mass of the blastocyst. ES cells have the ability to differentiate
      into all three germ layers and have unlimited growth potential under certain
      culture conditions. The great advantage of ES cells is the ability to obtain
      large amounts of tissue for biochemical studies as compared with preimplantation
      embryos. To examine in greater detail the biological actions of the insulin
      family of growth factors, the expression of their cognate receptors on ES cells
      was examined. ES cells were cultured in DMEM medium supplemented with leukemia
      inhibitory factor (LIF) to maintain the undifferentiated state. Receptor
      expression was evaluated at the mRNA level using the reverse transcription
      polymerase chain reaction (RT-PCR), and at the protein level by radioactive
      labeled ligand-receptor binding assay. Using RT-PCR, mRNAs of all three growth
      factor receptors were detected in ES cells. Messenger RNA from ES cells was
      reverse transcribed into cDNA by AMV reverse transcriptase at 42 degrees C for 1
      hr. The reverse transcription reaction was amplified with Taq polymerase and
      specific primers for insulin, IGF-I, or IGF-II receptors by PCR. RT-PCR and the
      control plasmid cDNA PCR products were resolved electrophoretically on 3% agarose
      gels. Each amplified PCR product showed the predicted correct size.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8562063
TI  - Xenopus lipovitellin 1 is a Zn(2+)- and Cd(2+)-binding protein.
AB  - This report discusses the identification of a Zn(2+)- and Cd(2+)-binding protein
      of Xenopus laevis that is abundant in vitellogenic oocytes and in embryos from
      fertilization to stage 46. Oocyte or embryo homogenates were fractionated by SDS
      PAGE, blotted onto nitrocellulose, and probed with 65Zn2+ or 109Cd2+. The
      resulting autoradiograms showed binding of both radionuclides to a protein,
      designated pCdZn. Freon extraction of oocyte and embryo homogenates showed pCdZn
      to be a yolk protein. When pCdZn was isolated from oocyte homogenates by ammonium
      sulfate precipitation, delipidation, and chromatography, it co-purified with
      lipovitellin 1. The amino acid composition of pCdZn closely resembled the
      reported composition of lipovitellin 1 and the molecular weight of purified pCdZn
      (approximately 115 kD) corresponded to reported values for lipovitellin 1 (111
      121 kD). Amino acid sequence analyses of five peptides derived from pCdZn yielded
      94% identity to the reported sequence of lipovitellin 1, deduced from the DNA
      sequence of the Xenopus vitellogenin A2 precursor gene. Based on these findings,
      pCdZn was identified as lipovitellin 1. This study suggests that lipovitellin 1
      is the major storage protein for zinc in mature oocytes and developing embryos of
      Xenopus laevis.

PMID- 8562064
TI  - Analysis of stimulatory and inhibitory amino acids for development of hamster one
      cell embryos in vitro.
AB  - Hamster embryo development to the blastocyst stage in vitro can be modulated by
      amino acids. This series of experiments employed both empirically and
      statistically designed approaches to elucidate which of 20 amino acids inhibit or
      stimulate development and to devise a complement of amino acids that best
      supports in vitro development of hamster 1-cell embryos. Development and/or mean
      cell number were significantly inhibited by the presence of leucine, tyrosine,
      valine, isoleucine, phenylalanine, arginine, methionine, or cysteine (at 0.5 mM)
      and isoleucine, phenylalanine, or tryptophan (at 0.05 mM). Three amino acids-
      glutamine, taurine, and glycine--were stimulatory and in combination improved
      development; the culture medium containing these amino acids was designated
      Hamster Embryo Culture Medium-5. Moreover, addition of another eight amino acids-
      asparagine, aspartic acid, serine, glutamic acid, histidine, lysine, proline and
      cysteine (medium designated HECM-6)--had a significant stimulatory effect on
      development over previously formulated culture media for hamster embryos. These
      results demonstrated that amino acids, alone and in combination, can markedly
      stimulate or inhibit hamster embryo development in vitro up to the blastocyst
      stage. Embryo transfer experiments showed that HECM-5 and -6 (chemically defined,
      protein-free culture media) supported normal preimplantation embryo development
      in vitro. This study also indicates that empirically designed embryo culture
      media formulations can be as effective as those obtained by application of
      statistical methodologies.

PMID- 8562065
TI  - Carbendazim (MBC) disrupts oocyte spindle function and induces aneuploidy in
      hamsters exposed during fertilization (meiosis II).
AB  - Peri-fertilization exposure to Carbendazim (MBC; a microtubule poison) induces
      infertility and early pregnancy loss in hamsters. Presently, both in vivo and in
      vitro techniques were employed to characterize the effects of MBC on cellular
      aspects of fertilization in hamsters. Exposure to MBC during either in vivo or in
      vitro fertilization (IVF) induced identical morphological abnormalities in the
      maternal chromatin of zygotes and embryos. These abnormalities included either
      multiple second polar bodies (PB2), and/or multiple small female pronuclei (PN),
      or meiotic arrest. Multiple PB2, multiple female PN, multiple PB2 with multiple
      female PN, or meiotic arrest were exhibited by approximately 31%, 15%, 12%, and
      2% of the in vivo zygotes; and 3%, 16%, 36%, and 20% of IVF zygotes,
      respectively. The effects of MBC persisted to day 2 of pregnancy as indicated by
      decreased (P < 0.05) embryo development to the two-cell stage and the presence of
      micronuclei in 6% of two-cell embryos from MBC-treated females.
      Immunofluorescence analysis of microtubules (MTs) confirmed that MBC disrupted
      spindle MTs during IVF. Numerical chromosome analysis revealed that a single dose
      of MBC administered during in vivo fertilization induced aneuploidy in the
      resulting pronuclear-stage zygotes. The present data point to two mechanisms by
      which peri-fertilization MBC exposure may induce early pregnancy loss: 1)
      arrested meiosis with no zygotic cleavage; or 2) induction of zygotic aneuploidy
      with subsequent developmental arrest.

PMID- 8562066
TI  - Increased accessibility of the N-terminus of testis-specific histone TH2B to
      antibodies in elongating spermatids.
AB  - Changes in chromatin structure during spermatogenesis were investigated using a
      monoclonal antibody that immunoreacts with the N-terminus of the testis-specific
      histone TH2B. This monoclonal antibody, which had been raised against rat
      tyrosine hydroxylase (TH), cross-reacted with TH2B because of sequence homology
      at the N-termini of TH and TH2B. The epitope was localized to the N-terminus of
      TH2B as trypsin-digested chromatin which lacked the N-terminal tail did not react
      with anti-TH and preincubating anti-TH with a synthetic peptide made from the
      homologous sequence between TH2B and TH inhibited its binding to TH and TH2B. In
      histological sections of rat testis, the primary spermatocytes and round
      spermatids immunoreacted weakly, whereas elongating spermatids at steps 10-12
      immunoreacted intensely with anti-TH. Increased staining of elongating spermatids
      was also observed in mouse and hamster by immunohistochemistry. However,
      immunoblotting proteins extracted from separated rat testis cells showed no
      increase in the TH2B content of these late steps of spermatids. The apparent
      increase in the immunohistochemical staining corresponds to increased
      accessibility of the epitope in the elongating spermatids. This indicated that
      the N-terminus of TH2B is less tightly bound to DNA or to other proteins at this
      time in preparation for the removal of TH2B and other histones.

PMID- 8562067
TI  - Localization of epitopes for monoclonal antibodies at the N-terminus of the
      porcine zona pellucida glycoprotein pZPC.
AB  - Zona pellucida glycoproteins play an important role in fertilization. In this
      study, attempts have been made to identify and define epitopes of monoclonal
      antibodies (mAbs) possessing contraceptive efficacy in vitro. The porcine zona
      glycoprotein pZPC, a homologue of mouse/human ZP3, was reduced and alkylated and
      subsequently digested with trypsin. Reverse-phase HPLC of the tryptic digest
      yielded twenty two peaks (T1-T22). When tested against mAbs reactive against
      sequential determinants on pZPC, T11 was immunoreactive with two mAbs, mAb-455
      and mAb-467, as shown by antigen inhibition ELISA. IC50 values of 3.1 nM and 8.6
      nM were recorded versus mAb-455 and mAb-467 respectively, and approximated the
      IC50 values obtained with intact pZPC. Amino acid analysis, Edman degradation,
      and FAB-MS identified T11 as the N-blocked decapeptide pyro-Gln-Pro-Val-Trp-Gln
      Asp-Glu-Gly-Gln-Arg derived from the N-terminus of pZPC. Synthesis of overlapping
      octapeptides further identified VWQDE and WQDE as the minimum motifs with
      antigenic activity for mAb-455 and mAb-467, respectively. Glycine replacement
      peptides confirmed residues W,Q,E as critical for binding mAb-455 and W,Q,D,E as
      critical for binding mAb-467. Both mAbs inhibited binding of boar sperm to zona
      encased porcine oocytes. These results, the first to define peptide epitopes of
      porcine zona glycoprotein, will assist in the design of an immunocontraceptive
      vaccine based on synthetic peptides corresponding to pZPC or its homologues in
      other species.

PMID- 8562068
TI  - Bovine oviduct-specific glycoprotein: a potent factor for maintenance of
      viability and motility of bovine spermatozoa in vitro.
AB  - In the cow, a specific glycoprotein--bovine oviduct-specific glycoprotein (BOGP)-
      is secreted by the epithelial cells of the oviduct at the follicular stage of the
      estrous cycle. In this study, we examined the effects of purified BOGP on the
      viability and motility of bovine spermatozoa in culture in vitro. Frozen-thawed
      bovine spermatozoa were incubated in modified Tyrode's solution (TALP) that
      contained purified BOGP (TALP-BOGP). In TALP-BOGP, both the viability and
      motility of bovine spermatozoa were more effectively maintained than in the
      control medium without any added protein. The increases in both the viability and
      motility of spermatozoa were dose-dependent. Spermatozoa were also incubated in
      TALP medium supplemented with bovine serum albumin, egg albumin, lactalbumin, or
      gastric mucin, and their viability and motility in these media were compared with
      that in TALP-BOGP. Both the viability and motility of spermatozoa were more
      effectively maintained in TALP-BOGP throughout a 12-hr incubation than in other
      media tested. An immunolabeling study demonstrated that a monoclonal antibody
      specific for BOGP reacted with the posterior region of the head, the middle
      portion, and the tail of spermatozoa that had been incubated with TALP-BOGP,
      suggesting that BOGP becomes specifically associated with particular regions of
      the spermatozoon. These results suggest that BOGP is a potent factor for
      maintenance of the viability and motility of sperm. On the basis of the present
      results, we also propose that BOGP may play an important role in sperm functions
      during the reproductive process.

PMID- 8562069
TI  - Analysis of the motility parameters of in vitro hyperactivated hamster
      spermatozoa.
AB  - Golden hamster cauda epididymal spermatozoa under in vitro capacitating
      conditions exhibited time-dependent transformation of motility pattern, and the
      frequency of occurrence of a particular motility type was found to be dependent
      on the depth of the motility chamber used. The nonhyperactivated spermatozoa with
      planar motility were the most predominant at 0 hr irrespective of the depth of
      the motility chamber. But spermatozoa with the helical motility pattern were not
      detectable up to 6 hr when the Makler chamber was used, whereas in both the slide
      chamber and cannula, by 2 hr such spermatozoa constituted 90% of the total
      spermatozoa. However, by 6 hr the hyperactivated circular moving spermatozoa were
      the predominant type in all the chambers. Sperm motility chamber depths were also
      found to effect the motility parameter values of hamster spermatozoa, but this
      effect was also found to be dependent on the type of motility. Increase in
      chamber depth did not alter any of the motility parameter values of spermatozoa
      with hatchet type of motility and only increased the amplitude of lateral head
      displacement (ALH) in planar type. But in spermatozoa with the helical type of
      motility, an increase in chamber depth increased the progressive velocity (VSL),
      path velocity (VAP), curvilinear velocity (VCL), straightness (STR), linearity
      (LIN), and ALH. In spermatozoa with the circular type of motility, an increase in
      VSL, VAP, VCL, and ALH was also observed, but STR and LIN decreased. The
      hyperactivated spermatozoa could be distinguished from the nonhyperactivated
      spermatozoa because the former were swimming in circles, had low progressive
      velocity, decreased straightness and linearity of path, and also exhibited an
      increase in the amplitude of lateral head displacement compared to the
      nonhyperactivated spermatozoa. Further, the spermatozoa with helical motility
      could be differentiated from the nonhyperactivated, circular, and hatchet
      spermatozoa in that they had the highest VSL, VAP, VCL, and ALH. Spermatozoa with
      hatchet movement were slow and exhibited very low STR and LIN. Thus the motility
      parameters could be used to distinguish the nonhyperactivated and hyperactivated
      distal cauda epididymal spermatozoa.

PMID- 8562070
TI  - Bovine cumulus cell expansion does not depend on the presence of an oocyte
      secreted factor.
AB  - Communication between the oocyte and its somatic cells has been shown to be
      important in oocyte development. Here we examined how the oocyte may be involved
      in bovine cumulus cell expansion. Intact bovine cumulus oocyte complexes (COC)
      were obtained by puncturing antral follicles. From the intact COC, oocytectomised
      complexes (OOX) were produced by micro surgical removal of the oocyte. Clumps of
      cumulus cells (CC) were obtained by micro-dissection. Intact or OOX complexes or
      CC were matured in the presence of fetal calf serum and hFSH (6 mlU/ml) for 24 hr
      and the degree of expansion measured. The presence of the oocyte is not essential
      to allow bovine cumulus expansion to occur as expansion occurred in all groups.
      Murine OOX complexes from eCG primed 35-40-day-old C57BL6/CBA F1 hybrids (known
      to require the presence of an oocyte secreted factor for cumulus expansion) were
      cultured with or without denuded bovine oocytes (1 oocyte/microliter). Murine OOX
      complexes expanded only in the presence of denuded bovine oocytes. Thus some
      factor produced by bovine oocytes enabled expansion of murine OOX complexes. To
      determine whether the factor is secreted by bovine oocytes, murine OOX were
      cultured with or without media conditioned by bovine oocytes (1 oocyte/microliter
      for 4 hr). Significant expansion of murine OOX occurred in media conditioned by
      bovine oocytes. This shows that the cumulus expansion enabling effect of bovine
      oocytes is released into the surrounding media. Media conditioned by bovine
      oocytes and then frozen for up to 1 month showed that the activity by the factor
      can withstand freezing.

PMID- 8562071
TI  - Analysis of the chromosome complement of frozen-thawed mouse oocytes after
      parthenogenetic activation.
AB  - Frozen-thawed mouse oocytes were artificially activated with Sr2+ and analyzed
      cytogenetically at the first cleavage division to examine the behavior of the
      maternal chromosomes independently of the paternal complement. There was no
      significant difference in the rate of activation between frozen-thawed and
      freshly collected oocytes and the majority of oocytes (> 90%) had a normal
      haploid chromosome constitution. The incidence of second polar body retention in
      frozen-thawed oocytes was low and did not differ significantly from that observed
      in fresh oocytes and oocytes exposed to dimethylsulfoxide (DMSO) at 0 degree C or
      37 degrees C for extended periods beyond those required for protection. The
      frequency of aneuploidy was similar for frozen-thawed and fresh oocytes but
      oocytes held at 0 degree C without DMSO or held at 37 degrees C with DMSO for 1
      hr showed a 2.5 and 12-fold increase in the frequency of aneuploidy compared with
      oocytes subjected to a conventional oocyte/embryo freezing regime. It is
      concluded that the procedures used in successful oocyte cryopreservation do not
      increase the incidence of chromosomal abnormalities of maternal origin in the
      resulting embryos.

PMID- 8562072
TI  - Tempting fate and commitment in the developing forebrain.

PMID- 8562073
TI  - Long-term depression properties in a simple system.
AB  - Long-term depression (LTD) in pairs of cultured rodent hippocampal neurons was
      examined to study the molecular basis of this form of synaptic plasticity. We
      have previously characterized two components of transmitter release: a
      synchronous, fast phase that requires synaptotagmin I, and an asynchronous, slow
      component that persists in the absence of synaptotagmin I. Are these two release
      components differentially affected by the presynaptic changes of LTD, or is the
      mechanism of plasticity common to both? We find that LTD is expressed as parallel
      changes in the fast and slow components of release, and that this form of
      synaptic plasticity is still seen in the absence of functional synaptotagmin I.
      Any alterations in the presynaptic release machinery observed during LTD thus
      involve mechanisms shared by both modes of release.

PMID- 8562074
TI  - Molecular basis of charge movement in voltage-gated sodium channels.
AB  - Voltage-dependent movement of a sodium channel S4 segment was examined by
      cysteine scanning mutagenesis and testing accessibility of the residues to
      hydrophilic cysteine-modifying reagents. These experiments indicate that 2
      charged S4 residues move completely from an internally accessible to an
      externally accessible location in response to depolarization by passage through a
      short "channel" in the protein. The energetic problems of S4 movement have thus
      been solved in the same way that may ion channels achieve highly selective and
      rapid ion permeation through an open pore, by restricting the contact region
      between the permion and its channel.

PMID- 8562075
TI  - A strongly interacting pair of residues on the contact surface of charybdotoxin
      and a Shaker K+ channel.
AB  - Charybdotoxin, a peptide neurotoxin of known molecular structure, blocks Shaker
      K+ channels by binding to a receptor at the outer opening of the ion conduction
      pathway. Analysis of variants of CTX at position 29 and of Shaker at position 449
      shows that these two residues interact closely in the channel-toxin complex. The
      CTX mutation M29I leads to a slight strengthening of block when tested on Shaker
      449T; the same CTX mutation weakens block 1700-fold when tested on Shaker-449F.
      The known position of CTX-29 on the toxin's interaction surface thus locates
      Shaker-449 within 5 A of the pore axis of the closed channel. All four subunits
      must carry the 449F mutation to produce a highly toxin-insensitive channel.

PMID- 8562076
TI  - Cerebellar contributions to cognition.

PMID- 8562077
TI  - Spatial localization of the K+ channel selectivity filter by mutant cycle-based
      structure analysis.
AB  - The structurally well-characterized scorpion toxin Agitoxin2 inhibits ion
      permeation through Shaker K+ channels by binding to the external pore entryway.
      Scanning mutagenesis identified a set of inhibitor residues critical for making
      energetic contacts with the channel. Using thermodynamic mutant cycle analysis,
      we have mapped channel residues relative to the known inhibitor structure. This
      study constrains the position of multiple channel residues within the pore
      forming loops; in one stretch, we have been able to map five out of seven
      contiguous residues to the inhibitor interaction surface, including those
      involved in ion selectivity. One interaction in particular, that of K27M on the
      inhibitor with Y445F on the channel, is unique in that it depends on the K+ ion
      concentration. These results reveal a shallow vestibule formed by the pore loops
      at the K+ channel entryway. The selectivity filter is located at the center of
      the vestibule close to (approximately 5 A) the extracellular solution.

PMID- 8562078
TI  - Exposure of residues in the cyclic nucleotide-gated channel pore: P region
      structure and function in gating.
AB  - In voltage-gated ion channels and in the homologous cyclic nucleotide-gated (CNG)
      channels, the loop between the S5 and S6 transmembrane segments (P region) is
      thought to form the lining of the pore. To investigate the structure and the role
      in gating of the P region of the bovine retinal CNG channel, we determined the
      accessibility of 11 cysteine-substituted P region residues to small, charged
      sulfhydryl reagents applied to the inside and outside of membrane patches in the
      open and closed states of the channel. The results suggest that the P region
      forms a loop that extends toward the central axis of the channel, analogous to
      the L3 loop of bacterial porin channels. Furthermore, the P region, in addition
      to forming the ion selectivity filter, functions as the channel gate, the
      structure of which changes when the channel opens.

PMID- 8562079
TI  - Intracellular calcium directly inhibits potassium M channels in excised membrane
      patches from rat sympathetic neurons.
AB  - Complex effects of altering intracellular [Ca2+] on M-type K+ currents have
      previously been reported using whole-cell current recording. To study the direct
      effect of Ca2+ on M-channel activity, we have applied Ca2+ to the inside face of
      membrane patches excised from rat superior cervical sympathetic ganglion cells.
      Ca2+ rapidly and reversibly inhibited M-channel activity in 28/44 patches by up
      to 87%, with a mean IC50 of 100 nM. This effect persisted in the absence of ATP,
      implying that it was not due to phosphorylation/dephosphorylation. A similar
      effect was observed in 13/13 cell-attached patches when cells were transiently
      "Ca(2+)-loaded" by adding 2 mM Ca2+ to a 25 mM K+ solution bathing the extrapatch
      cell membrane. These observations provide new evidence that Ca2+ can directly
      inhibit M channels, so supporting the view that Ca2+ might mediate M current
      inhibition following muscarinic receptor activation.

PMID- 8562080
TI  - Calcineurin regulates M channel modal gating in sympathetic neurons.
AB  - The M current regulates neuronal excitability, with its amplitude resulting from
      high open probability modal M channel behavior. The M current is affected by
      changing intracellular calcium levels. It is proposed that internal calcium acts
      by regulating M channel modal gating. Intracellular application of a preactivated
      form of the calcium-dependent phosphatase calcineurin (CaN420) inhibited the
      macroscopic M current, while its application to excised inside-out patches
      reduced high open probability M channel activity. Addition of ATP reversed the
      action of CaN420 on excised patches. The change in M channel gating induced by
      CaN420 was different from the effect of muscarine. A kinetic model supports the
      proposition that shifts in channel gating induced by calcium-dependent
      phosphorylation and dephosphorylation control M current amplitude.

PMID- 8562081
TI  - Mean genes.

PMID- 8562082
TI  - Gadolinium uncouples mechanical detection and osmoreceptor potential in
      supraoptic neurons.
AB  - Stretch-sensitive ion channels are ubiquitous, yet evidence of their role in
      mechanotransduction remains scarce. The presence of stretch-inactivated cation
      channels in supraoptic neurons is consistent with the osmoreceptor potentials
      regulating vasopressin release. However, whether osmosensitivity depends on
      mechanical gating and ion flux through stretch-inactivated channels is unknown.
      Here we report that changes in channel open probability associated either with
      modification of pipette pressure or with external osmolality selectivity result
      from variations in closed time. While channel mechanosensitivity and osmotically
      evoked changes in cell volume are not affected by gadolinium, similar
      concentrations of the lanthanide inhibit cation permeation through the single
      channels and macroscopic osmoreceptor potentials. Mechanotransduction through
      stretch-inactivated channels is therefore necessary for osmoreception in
      supraoptic neurons.

PMID- 8562083
TI  - Extracellular proteins needed for C. elegans mechanosensation.
AB  - The mec-5 and mec-9 genes encode putative extracellular proteins that allow a set
      of six touch receptor neurons in C. elegans to respond to gentle touch. MEC-5 is
      a collagen made by the epidermal cells that surround the touch cells. Mutations
      causing touch insensitivity affect the Gly-X-Y repeats of this collagen. mec-9
      produces two transcripts, the larger of which is expressed in the touch cells and
      two PVD neurons. This transcript encodes a protein with 5 Kunitz-type protease
      inhibitor domains, 6 EGF-like repeats (2 of the Ca(2+)-binding type), and a
      glutamic acid-rich region. Missense mutations causing touch insensitivity affect
      both the EGF-like and Kunitz domains. Since mec-9 loss of function mutations
      dominantly enhance the touch insensitive phenotype of several mec-5 mutations,
      MEC-5 and MEC-9 may interact. We propose that these proteins provide an
      extracellular attachment point for the mechanosensory channels of the touch
      cells.

PMID- 8562084
TI  - Calmodulin is the divalent cation receptor for rapid endocytosis, but not
      exocytosis, in adrenal chromaffin cells.
AB  - Exocytosis and the ensuing rapid endocytosis in adrenal chromaffin cells are both
      Ca(2+)-dependent phenomena but differ in their divalent cation specificity,
      implying distinct Ca2+ receptors for the two processes. To ascertain whether
      calmodulin is the Ca2+ receptor for either process, we blocked its function by
      introducing calmodulin-binding peptides or anti-calmodulin antibodies into these
      cells. Exo/endocytosis was followed by measurement of cell membrane capacitance.
      Rapid endocytosis, but not exocytosis, was abolished by these treatments,
      indicating that calmodulin is the Ca2+ receptor for rapid endocytosis but is not
      involved in exocytosis. The principal calmodulin target is not protein
      phosphatase-2B, as antagonism of this enzyme did not inhibit but accelerated
      rapid endocytosis. Calmodulin may thus regulate both the rate and extent of rapid
      endocytosis by distinct pathways.

PMID- 8562085
TI  - Transfer of 1,4-dihydropyridine sensitivity from L-type to class A (BI) calcium
      channels.
AB  - L-type Ca2+ channels are characterized by their unique sensitivity to organic
      Ca2+ channel modulators like the 1,4-dihydropyridines (DHPs). To identify
      molecular motifs mediating DHP sensitivity, we transferred this sensitivity from
      L-type Ca2+ channels to the DHP-insensitive class A brain Ca2+ channel, BI-2.
      Expression of chimeras revealed minimum sequence stretches conferring DHP
      sensitivity including segments IIIS5, IIIS6, and the connecting linker, as well
      as the IVS5-IVS6 linker plus segment IVS6. DHP agonist and antagonist effects are
      determined by different regions within the repeat IV motif. Sequence regions
      responsible for DHP sensitivity comprise only 9.4% of the overall primary
      structure of a DHP-sensitive alpha 1A/alpha 1S construct. This chimera fully
      exhibits the DHP sensitivity of channels formed by L-type alpha 1 subunits. In
      addition, it displays the electrophysiological properties of alpha 1A, as well as
      its sensitivity toward the peptide toxins omega-agatoxin IVA and omega-conotoxin
      MVIIC.

PMID- 8562086
TI  - Dominant role of mitochondria in clearance of large Ca2+ loads from rat adrenal
      chromaffin cells.
AB  - Cytosolic Ca2+ (Ca2+c) clearance from adrenal chromaffin cells was studied by
      whole-cell patch clamp and indo-1 Ca2+ photometry after influx of Ca2+ through
      voltage-dependent Ca2+ channels. We isolated the rates of Ca2+c clearance by
      several mechanisms using combinations of the following agents (with their
      expected targets): Li+ or TEA substituted for Na+ (Na(+)-Ca2+ exchange), 1 mM
      La3+ applied after the depolarization (Na(+)-Ca2+ exchange and plasma membrane
      Ca(2+)-ATPase), 1 microM thapsigargin (pumping into reticular stores), and 2
      microM carbonyl cyanide m-chlorophenylhydrazone (uptake into mitochondria).
      Remarkably, whenever [Ca2+]c rose above approximately 500 nM, Ca2+c clearance by
      mitochondria exceeded clearance by either Na(+)-Ca2+ exchange or the Ca2+ pumps
      of the plasma and reticular membranes. As [Ca2+]c fell again, Ca2+ reemerged from
      mitochondria, prolonging the final return to basal levels.

PMID- 8562087
TI  - Asynchronous onset of odorant receptor expression in the developing zebrafish
      olfactory system.
AB  - The functional identity of an olfactory neuron is determined in large part by the
      odorant receptors it expresses. As an approach toward understanding the events
      that underlie the specification of olfactory neurons, we have examined the
      patterns of odorant receptor gene expression in the developing zebrafish.
      Surprisingly, we find that the onset of specific odorant receptor expression
      occurs asynchronously in the developing olfactory placode. Our results suggest
      that odorant receptor expression is not strictly stochastic, but rather is
      governed by temporally regulated cues during development. Moreover, by
      restricting the number of receptor genes competent for transcription at different
      times of development, temporal waves of expression may provide a mechanism for
      simplifying the regulation of the large odorant receptor gene family.

PMID- 8562088
TI  - Neuroglia and pioneer neurons express UNC-6 to provide global and local netrin
      cues for guiding migrations in C. elegans.
AB  - Netrins are laminin-related proteins that guide circumferential migrations on the
      ectoderm. To understand how netrin cues direct cell movements, we examined the
      expression of nematode netrin UNC-6 from embryo to adult. UNC-6 is expressed in
      12 types of neuroglia and neurons, creating a hierarchy of netrin cues in the
      developing nervous system. Comparing gene expression pattern with in vivo
      phenotypes, we suggest how multiple netrin cues, each with a characteristic role,
      guide cells and axons during development. We also present the molecular analysis
      of selective loss-of-function and null alleles. The results indicate that the
      biological activities of netrins are mediated through distinct protein domains.
      Subtle mutations in domain VI can produce selective defects in both direction-
      and tissue-specific guidance. EGF-like module V-2 is essential for dorsal
      guidance activity; we infer this module is important for interactions between UNC
      6 and the dorsal guidance receptor UNC-5.

PMID- 8562089
TI  - Generation of cerebellar interneurons from dividing progenitors in white matter.
AB  - The traditional view of the external granular layer of the cerebellar cortex
      giving rise to interneurons has been challenged by recent studies with quail
      chick chimeras. To clarify the time and site of origins of interneurons, a
      retrovirus carrying the beta-galactosidase gene was injected into the deep
      cerebellar tissue or external granular layer of postnatal day 4/5 rats to label
      dividing progenitors. After deep cerebellar tissue injection, unipolar cells were
      found initially in white matter at 2 days postinjection and subsequently in the
      internal granule and molecular layers 4-6 days postinjection. Morphologically
      defined basket, stellate, and Golgi neurons were clearly identified by 20 days
      postinjection. In contrast, retroviral labeling of cells in the external granular
      layer produced only granule neurons in the internal granule layer. Thus, dividing
      progenitors in the cerebellar white matter migrate through the white matter into
      the cortex before differentiating into a variety of cortical interneurons.

PMID- 8562090
TI  - Molecular enhancement of memory formation.

PMID- 8562091
TI  - A role for gradient en expression in positional specification on the optic
      tectum.
AB  - The optic tectum, the primary visual center in non-mammalian vertebrates,
      receives retinal fibers in a topographically ordered manner. en (en-1 and en-2,
      homologs of the Drosophila segment polarity gene engrailed) is expressed in the
      tectal primordium in a rostrocaudal gradient, around the stage when the polarity
      of the retinotectal projection map is being determined. Here we report that
      scattered en expression, caused by retroviral gene transfer, perturbed the
      retinotopic order. Nasal retinal fibers, which normally recognize the caudal side
      of the tectum (strong en expression side) as a target, arborized at ectopic
      sites, as if they found their targets, or degenerated. Temporal retinal fibers,
      which normally recognize the rostral side of the tectum (weak en expression side)
      as a target, were also affected in some cases by degeneration or prevention of
      innervation in the tectum. These results suggest that gradient en expression
      defines the positional identity of the tectum along the rostrocaudal axis.

PMID- 8562092
TI  - Engrailed, retinotectal targeting, and axonal patterning in the midbrain during
      Xenopus development: an antisense study.
AB  - Axonal tracts in the vertebrate brain seem to respect domains of homeobox gene
      expression. To test the role of engrailed in tract formation in the midbrain, we
      inhibited its expression using antisense (AS) oligonucleotides. Phosphorothioate
      modified AS oligos caused navigational errors in both the optic projection (OP)
      and the intertectal commissure (ITC). These oligos, however, also inhibited bFGF
      binding to the brain. To determine whether these tract phenotypes were due to
      inhibition of bFGF function or engrailed expression, we used partially
      phosphorothioate-modified (pp) oligos, which inhibit engrailed expression but do
      not affect bFGF binding. These ppAS oligos caused the ITC phenotype but had no
      effect on the OP. Thus, interference with bFGF function correlates with the OP
      phenotype, while the ITC phenotype is directly related to engrailed expression.

PMID- 8562093
TI  - Periventricular heterotopia: an X-linked dominant epilepsy locus causing aberrant
      cerebral cortical development.
AB  - Periventricular heterotopia (PH) involves dramatic malformations of the human
      cerebral cortex. Here we show that PH is closely linked to markers in distal Xq28
      (maximal two-point lod score = 4.77 for F8C at theta = 0; maximal multipoint lod
      score = 5.37), so that affected females are obligatory mosaics for the mutation;
      that PH is lethal to at least some affected males; that PH malformations consist
      of well-differentiated cortical neurons filling the adult subependymal zone; and
      that individuals with PH are at high risk for epilepsy, though they have no other
      neurological or external stigmata. The PH gene may represent an important
      epilepsy susceptibility locus in addition to playing a key role in normal
      cortical development.

PMID- 8562094
TI  - Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during
      multiple forms of hippocampal synaptic plasticity.
AB  - Phosphorylation of the transcription factor CREB is thought to be important in
      processes underlying long-term memory. It is unclear whether CREB phosphorylation
      can carry information about the sign of changes in synaptic strength, whether
      CREB pathways are equally activated in neurons receiving or providing synaptic
      input, or how synapse-to-nucleus communication is mediated. We found that Ca(2+)
      dependent nuclear CREB phosphorylation was rapidly evoked by synaptic stimuli
      including, but not limited to, those that induced potentiation and depression of
      synaptic strength. In striking contrast, high frequency action potential firing
      alone failed to trigger CREB phosphorylation. Activation of a submembranous Ca2+
      sensor, just beneath sites of Ca2+ entry, appears critical for triggering nuclear
      CREB phosphorylation via calmodulin and a Ca2+/calmodulin-dependent protein
      kinase.

PMID- 8562096
TI  - Respiratory complications after surgical treatment of esophageal cancer. A study
      of 309 patients according to the type of resection.
AB  - This study analyzes the respiratory complications in a retrospective study of 309
      resections for esophageal cancer. We mainly performed two types of resections
      according to the height of the tumor: the Ivor-Lewis resection for middle
      thoracic lesions (182 cases), and the Akiyama resection for upper thoracic
      lesions (127 cases). We compared the respiratory complications occurring after
      these two procedures. Our overall mortality and morbidity rates were,
      respectively, 9% and 37%. In our series, the mortality rate was 4 times higher
      after the Akiyama procedure than after the Ivor-Lewis procedure, and the
      morbidity was twice as high. Respiratory complications accounted for 64% of the
      postoperative deaths. The Akiyama procedure yielded more respiratory
      complications, especially isolated bronchopneumonia and necrosis of the trachea
      or of the right or left main bronchus. Respiratory complications accounted for
      53% of morbidity, mainly recurrent nerve paralysis with false passages and stasis
      in the transplant. Both are directly related to the surgical act and often result
      in bronchopneumonia. Rather than the surgical technique or the skill of the
      surgeon, it seems that local factors, such as the position of the tumor on the
      esophagus, increased the incidence of recurrent nerve paralysis following the
      Akiyama procedure. However, the rate of respiratory complications remained high
      after the Ivor-Lewis procedure. Patient history, which sometimes included a
      previous ENT cancer, must be taken into account, as well as the gravity of the
      operation and the duration of the intubation. Frequent false passages and reflux
      must be fought by intensive physiotherapy and, when necessary, by early
      tracheotomy before the patient develops postoperative acute respiratory distress
      syndrome.

PMID- 8562095
TI  - Turning a blind eye to cortical receptive fields.

PMID- 8562097
TI  - Thoracoscopic mediastinal lymph node dissection: an experimental study in pigs.
AB  - Thoracoscopic lobectomy is feasible and can be performed correctly in terms of
      anatomy. Its application in bronchial carcinoma is often criticized, partly
      because of incomplete mediastinal lymph node dissection (MLD). We therefore
      developed the technique and studied the completeness of MLD in an animal
      experiment. Ten pigs were anesthetized and intubated with a double-lumen tube and
      the left lung was excluded from ventilation. Four trocars were inserted. Using a
      modified endo-Babcock clamp for traction we resected all ipsilateral
      tracheobronchial, pretracheal and paratracheal and paraesophageal lymph nodes
      (LNs) as well as nodes in the aortopulmonary window. An average of 19 +/- 5
      mediastinal LNs were removed. Macroscopic control through a thoracotomy did not
      show any residual LNs at the site of operation. Complete resection of all
      ipsilateral LNs in the paratracheal and paraesophageal region as well as the
      aortopulmonary window can be performed thoracoscopically in pigs. This may offer
      further perspectives in the thoracoscopic treatment of bronchial carcinoma.

PMID- 8562098
TI  - Improved 20-hour canine lung preservation with a new solution--ET-Kyoto solution.
AB  - We developed a new solution, ET-Kyoto (ET-K) solution, and compared its efficacy
      in 20 h lung preservation with that of Euro-Collins (EC) solution in a canine
      left lung transplantation model. The lungs were flushed with ET-K solution (ET-K
      group, n = 5), with EC solution plus prostaglandin E1 (PGE1) pretreatment (EC +
      PGE1 group, n = 6) or with EC solution (EC group, n = 6), and were stored at 4
      degrees C for 20 h. The function of left lung grafts was assessed 40, 70, and 130
      min after transplantation. The arterial pressure of oxygen (PaO2) in the ET-K
      group was significantly greater than in the EC + PGE1 group (p < 0.05 or p <
      0.01) and in the EC group (p < 0.01). The peak inspiratory pressure and wet to
      dry weight ratio in the ET-K group were significantly lower than in the EC + PGE1
      group and in the EC group (p < 0.05 or p < 0.01). Pulmonary vascular resistance
      in the ET-K group 130 min after reperfusion was significantly lower than in the
      EC group (p < 0.05). All the transplanted lungs in the EC + PGE1 group and the EC
      group showed histological evidence of pulmonary edema, whereas all in the ET-K
      group showed no signs of edema. We concluded that ET-K solution is superior to EC
      solution with or without PGE1 pretreatment in 20 h canine lung preservation.

PMID- 8562099
TI  - Extracorporeal membrane oxygenation and the treatment of critical pulmonary
      hypertension in congenital heart disease.
AB  - Certain forms of congenital heart disease (CHD) confer a high risk for the
      development of severe pulmonary hypertension before and after corrective cardiac
      surgery. Extracorporeal membrane oxygenation (ECMO) has theoretical benefits in
      the treatment of this complication in that it assures oxygenation, corrects acid
      base balance and provides haemodynamic support at the same time as allowing lung
      rest from ventilation. We examined our experience of the 117 children and
      neonates supported with ECMO between November 1989 and July 1993. Of these, five
      received support for critical pulmonary hypertension associated with congenital
      heart disease. They comprised three who had undergone surgical repair of CHD, one
      whose total anomalous pulmonary venous drainage was diagnosed and corrected
      whilst on ECMO and one neonate with functional pulmonary atresia. Pulmonary
      artery pressure (PAP) was estimated by Doppler echocardiography in all patients
      and confirmed invasively in two. The median systolic PAP was 46 (range 42-65)
      mmHg prior to ECMO. The median ratio of pulmonary to systemic arterial pressure
      (PAP/SAP) was 0.75 (0.70-0.92). Following ECMO of 16-120 h duration, the median
      systolic PAP was 34 (30-49) mmHg with PAP/SAP 0.50 (0.35-0.60). All patients
      survived and there were no complications related to ECMO. Extracorporeal membrane
      oxygenation is an effective treatment in critical pulmonary hypertension and
      should be considered in all patients in whom this is refractory to conventional
      measures.

PMID- 8562100
TI  - Modified surgical concept for fulminant pulmonary embolism.
AB  - Surgical intervention in fulminant pulmonary embolism (PE) is still associated
      with an overall 30% fatal outcome which increases to about 60% when
      cardiopulmonary resuscitation (CPR) is necessary. Despite unfavorable conditions
      like hemodynamic instability, failed lysis or CPR, the surgical strategy might
      have a certain impact on the patient's outcome since 30-40% of the surgical
      mortality is related to persistent right heart failure and early thromboembolic
      recurrence. From 1/88 to 8/94 a total of 25 patients (15 females, 10 men, mean
      age 57 [25-78]) years underwent emergency pulmonary embolectomy with the use of
      the heart-lung machine. Seventeen patients were operated upon between 1988 and
      1992. A standard approach by central pulmonary artery incision with extraction of
      adjacent pulmonary emboli using forceps, suction of Fogarty catheters was used.
      Six of these patients (35%) died, with four out of six operated upon under CPR.
      Since 1993 we have used a modified surgical strategy in eight patients. Five
      patients (63%) were operated on after or under CPR. In these cases, left and
      right pulmonary arteries were incised peripherally and all segmental arteries
      were desobliterated selectively using small suction devices. Thereafter the right
      atrium was opened and inspected. After removal of the inferior caval vein cannula
      all inferior body blood was taken with cardiotomy suction while both legs and the
      abdomen were massaged centripetally to mobilize additional fresh thrombotic
      material. In three cases up to 50 cm long thrombi could be delivered. All
      patients have survived to date with two patients receiving a LGM caval filter
      placed percutaneously after bilateral postoperative phlebography had revealed
      ongoing thrombotic disease. We conclude that selective desobliteration of every
      segmental pulmonary artery in combination with simultaneous clearance of major
      body veins from additional thrombotic material will probably lower surgical
      mortality in these critically ill patients.

PMID- 8562101
TI  - Free-hand sewn allografts, stentless (Prima Edwards) and stented (CESA) porcine
      bioprostheses. A comparative hemodynamic study.
AB  - In a retrospective, non-randomized study, the clinical and hemodynamic properties
      of 50 consecutively implanted hand-sewn allografts (group I), 50 stentless
      bioprostheses (group II) and 50 stented bioprostheses (group III) were compared.
      Preoperative hemodynamic and clinical data were identical in the three groups,
      except for age (group I: 54.4 +/- 8.7, group II: 67.0 +/- 5.1, group III: 70.0 +/
      5.1). Peak and mean gradients and flow characteristics with echo Doppler were
      performed at 1 week, 6 and 12 months. For the 21, 23 and 25 diameter prostheses,
      group differences between groups II and III in peak and mean gradients were not
      significant after 1 week and 1 year. In all groups, allografts had significantly
      lower gradients. Regurgitation (I-II) was present after 1 week and 1 year in
      group I: in 17/48 and 22/42 patients respectively, in group II 7/49 and 11/44
      patients and in group III: in 1/49 and 2/44 patients. Early mortality and
      morbidity were comparable in all groups. Allografts have superior hemodynamic
      properties. Differences in gradients in groups II and III were not significant,
      though differences in technique allowed the implantation of a larger
      bioprostheses in group II. Regurgitation was most prominent in the allograft
      group. Immediate postoperative results were not influenced by the type of
      prosthesis.

PMID- 8562102
TI  - The effect of pathophysiology on the surgical treatment of ischemic mitral
      regurgitation: operative and late risks of repair versus replacement.
AB  - Operative correction of ischemic mitral regurgitation (IMR) is associated with
      high risk approach. The objective of this retrospective study was to examine the
      interaction between the various underlying pathophysiologic mechanisms, the
      operative procedure, and their influence on short- and long-term outcomes. Over a
      10-year period starting January 1984, mitral valve repair or replacement was
      performed on 150 patients with IMR. The age range was 42-86, mean 67, years; 71
      (47%) were females; 139 (93%) were in NYHA functional class III or IV; 23 (15%)
      were reoperations; and 30 (20%) were in atrial fibrillation. Functional IMR due
      to annular dilatation or restrictive leaflet motion was present in 106 (71%), and
      structural IMR due to ruptured chordae or papillary muscle in 44 (29%). Mitral
      valve repair was performed in 94 (63%) with an annuloplasty ring employed in 80
      (85%) patients. Mitral valve replacement was performed in 56 (37%), with 40 (71%)
      receiving a bioprosthesis (32 Hancock and 8 Carpentier-Edwards valves) and 16
      (29%) a St. Jude valve. Coronary artery bypass graft surgery was performed in 139
      (93%) patients. The overall operative mortality (OM) was 14/150 (9.3%). The OM
      for repair was 9.5% compared to 8.9% for replacement (P = NS). There was higher
      OM in the elderly, particularly in the repair group (P = 0.053), and a trend
      towards reduced OM in the recent years of the study (P = NS). No predictors of OM
      were identified by multivariate logistic regression analysis. Long-term follow-up
      was 98% complete and ranged from 2-120, mean 31.2, months for a total of 935
      patient-years. The overall 5-year survival rate was 71 +/- 6%, with 91 +/- 5% for
      the replacement group compared to 56% +/- 10% for the repair group (P = 0.01).
      The functional subset of IMR who had a repair had the worse long-term survival
      (43 +/- 13%) compared to the structural/repair (76 +/- 13%) and
      structural/replacement groups (89 +/- 8%), and 92 +/- 7% for the
      functional/replacement group ((P = 0.0049). Multivariate logistic regression
      analysis identified the functional/repair group (hazards ratio 4.4; +/- 95%,
      confidence interval 1.6, 11, (P = 0.0031); and earlier years of surgery (hazards
      ratio 4.7; +/- 95% confidence interval 1.021; (P = 0.046) to be predictors of
      worse long-term survival. These results suggest that, in IMR, the underlying
      responsible pathophysiologic mechanisms appear to be the major determinants of
      survival, rather than the choice of the operative procedure.

PMID- 8562103
TI  - Technical aspects and late functional results of gastroepiploic bypass grafting
      (400 cases).
AB  - From January 1990 to February 1994, 400 patients (mean age 59 +/- 9 years)
      underwent myocardial revascularization using the right gastroepiploic artery
      (GEA) to bypass the right coronary artery trunk or branches. They represented 40%
      of all patients undergoing isolated coronary surgery during the same period, from
      19% in 1990 to 54% in 1994. Left ventricular function was normal in 32% of
      patients, moderately impaired in 62% and severely impaired in 6%. The GEA was
      used alone in six patients, associated with one internal mammary artery (IMA) in
      111 patients (two arterial grafts, 2.2 +/- 0.4 anastomoses) and with both IMAs in
      283 patients (three arterial grafts, 3.4 +/- 0.6 anastomoses); no vein graft was
      used. The rate of complete myocardial revascularization was 79%. Early mortality
      was 1.7% and influenced by left ventricular ejection fraction (P < 0.05).
      Complications occurred in 37 patients: myocardial infarction 4%, intra-aortic
      balloon pump 0.5%, reoperation for bleeding 0.5%, mediastinitis 0.25%. Early
      (15th postoperative day) angiographic control of the GEA graft was performed in
      104 patients operated from January 1990 to December 1991 and the patency rate was
      92%; anomalies of GEA were three occlusions, five stenoses, three competitive
      flow, no string or slender sign. Early functional results (3 +/- 1 months
      postoperatively) were studied in 192 patients during exercise test with medical
      treatment: 99% were symptom-free and 14% had electrocardiographic (ECG) ischemic
      modification significantly correlated with incomplete revascularization (P <
      0.01). The 2- and 4-year actuarial survival rate was 96.7 +/- 1.9%. The rate of
      late cardiac events was 2% patient/year; Angioplasty for GEA graft failure was
      required in four patients. A 2-year postoperative functional assessment without
      medical treatment was performed during exercise test in 66 patients who had
      received three arterial grafts: 98% were symptom-free and 26% had ECG ischemic
      modification significantly correlated with incomplete revascularization (P <
      0.01); during the same procedure, thallium myocardial scintigraphy was obtained
      in 50 patients: 18 patients (36%) had asymptomatic ischemic defects on exercise
      significantly correlated with incomplete revascularization and ECG ischemic
      changes (P < 0.01). However, posterior thallium defects demonstrated limited GEA
      flow at the maximum level of exercise in at least 8% of patients. Myocardial
      revascularization using the GEA can be achieved with minimal operative risk and
      offers satisfactory functional results and midterm survival rate.

PMID- 8562104
TI  - Haemodynamic and metabolic effects of surface rewarming after coronary
      revascularization.
AB  - Cardiac surgery is often associated with a postoperative increase in the
      patient's metabolic rate; surface rewarming has been suggested to decrease the
      energy expenditure by preventing hypothermia. Thirty patients, undergoing
      coronary revascularization, were randomly divided into two groups; after surgery
      group A was rewarmed by a new device that acts by both conduction and convection,
      while group B was just covered with cotton blankets. Blood, oesophagus and skin
      (thigh and foot) temperatures were recorded on admission to the intensive care
      unit (ICU) and 30, 60, 90, 180, 270, and 450 min later. Haemodynamic parameters,
      oxygen delivery, calculated oxygen consumption, and plasma lactate concentration
      were assessed as well. Group A warmed up quicker than group B as far as the skin
      was concerned while the core temperature was unaffected. Group A was also
      characterized by lower cardiac indices and oxygen consumption. As the occurrence
      of a dependence of oxygen consumption on delivery could be reasonably ruled out
      in warmed patients because blood lactate levels were lower than in the controls,
      we conclude that surface rewarming might have some positive effect in decreasing
      metabolic demand after cardiac surgery even if the patient's core temperature is
      little affected. The inhibition of skin temperature receptors could possibly
      explain this finding.

PMID- 8562105
TI  - Intravenous amiodarone vs propafenone for atrial fibrillation and flutter after
      cardiac operation.
AB  - The safety and efficacy of amiodarone and propafenone in converting atrial
      fibrillation or flutter after cardiac surgery were compared in a randomized
      double-blind trial. Eighty-four patients with sustained atrial tachyarrhythmias
      of more than 30 min' duration, stable hemodynamic status and neither preoperative
      atrial arrhythmias nor treatment with other antiarrhythmis drugs, were randomized
      to receive amiodarone (46 patients: 5 mg/kg over 15 min and then 15 mg/kg over
      the subsequent 24 h for non-converting) or propafenone (38 patients: 2 mg/kg over
      15 in and then 10 mg/kg over the subsequent 24 h for non-converting). Nine of the
      46 patients (19.5%) receiving amiodarone converted to sinus rhythm within 1 h
      following bolus injection compared with 17 of 38 patients (44.7%) treated with
      propafenone (P < 0.05). Within the 24 h study, 38 of 46 patients (82.6%) given
      amiodarone and 26 of 38 patients (68.4%) given propafenone were converted to
      sinus rhythm (P = NS). A significantly progressive reduction in ventricular
      response, already evident at 10th min from the start of treatment, was achieved
      in both groups of patients. Side effects occurred in six patients given
      propafenone (15.7%) and in five given amiodarone (10.8%) (P = NS). The two drugs
      were equally effective in converting postoperative atrial fibrillation and/or
      flutter after 24 h although propafenone was superior within the first hour.

PMID- 8562106
TI  - Strategies for routine biopsies in heart transplantation based on 8-year results
      with more than 13,000 biopsies.
AB  - The endomyocardial biopsy (EMB) in heart transplant recipients has been
      considered the "gold standard" for diagnosis of graft rejection (REJ). The
      purpose of this retrospective study is to develop long-term strategies (frequency
      and postoperative duration of EMB) for REJ monitoring. Between 1985 and 1992, 346
      patients (mean age 44.5 years, female patients = 14%) received 382 heart grafts.
      For graft surveillance EMBs were performed according to a fixed schedule
      depending on postoperative day and the results of previous biopsies. In the first
      year the average number (no.) of EMBs/patient was 20 with 19% positive for REJ in
      the first quarter, dropping to 7% REJ/EMB by the end of the first year. The
      percentage of REJ/EMB declined annually from 4.7% to 4.5%, 2.2% and less than 1%
      after the fifth year. Individual biopsy results in the first 3 postoperative
      months had little predictive value. Patients with fewer than two REJ (group 1),
      vs patients with two or more REJ in the first 6 postoperative months (group 2),
      were significantly less likely to reject in the second half of the first year
      (group 1: 0.29 +/- 0.6 REJ/patient; group 2:0.83 +/- 1.3 REJ/patient; P < 0.001)
      and third postoperative year (group 1:0.12 +/- 0.33 REJ/patients; group 2:0.46 +/
      0.93 REJ/patient; P < 0.05). In conclusion, routine EMBs in the first 3
      postoperative months have only limited predictive value, however the number of
      routine EMBs can be drastically reduced later depending on the intermediate
      postoperative REJ pattern.

PMID- 8562107
TI  - Unidentified retained left atrial myxoma: intra-operative detection by trans
      oesophageal echocardiography.
AB  - A 73-year-old woman underwent surgery for removal of a large left atrial myxoma
      diagnosed by transthoracic echocardiogram. At operation a large tumour was
      removed, and the left atrium and atrial septum closed. Trans-oesophageal
      echocardiography prior to weaning from cardiopulmonary bypass revealed that a
      smaller tumour, which had not been detected by visual inspection or palpation,
      remained within the left atrium. This was removed through the atrial septum, and
      the operation completed uneventfully. The patient made a full recovery.

PMID- 8562108
TI  - Complication of intra-aortic balloon pumping in a pediatric patient.
AB  - A serious complication was seen following insertion of an intra-aortic balloon
      pump in the ascending aorta in a pediatric patient. The catheter initially
      coursed to the left subclavian artery from which it folded upon before finding
      its way in the descending aorta. We recommend that a suitably curved J-tip
      guidewire be used to guide the IABP balloons distal to the aortic arch into the
      descending aorta, so as to avoid potentially fatal complications.

PMID- 8562109
TI  - Acute ascending aortic dissection combined with chronic degenerative thoraco
      abdominal aortic aneurysm.

PMID- 8562110
TI  - [Dobutamine stress echocardiography in patients after an acute myocardial
      infarct: what is the significance of arterial patency related to the infarct?].
AB  - BACKGROUND: Dobutamine stress echocardiography is a very promising technique for
      assessing myocardial viability, ischemia and prognosis in patients with a recent
      acute myocardial infarction. Recent studies have shown that the type of perfusion
      in the infarct-related artery also plays a role in the prognosis of these
      patients. PURPOSE: To evaluated in patients with non complicated infarction the
      ability of low-dose and high-dose dobutamine stress echocardiography to assess
      the presence of both viability and inducible ischemia and correlate the results
      with the patency of the infarct related artery and the accuracy to predict
      cardiac events during one year follow-up. PATIENTS AND METHODS: Fifty one
      consecutive in-hospital patients (47 male and four female, mean age 52 +/- 11
      years, range 31-75 years) with acute myocardial infarction were evaluated both by
      dobutamine stress echocardiography and by coronary angiography and followed-up
      for a mean of 12 +/- 8 months. RESULTS: With low-doses of dobutamine, the
      incidence of myocardial viability was 33% and with high-doses, the incidence of
      residual inducible ischemia was 41%. The patency of infarct-related artery showed
      significant correlation with score wall motion index for viability and for
      myocardial ischemia. Twenty four (47%) patients suffered cardiac events.
      Dobutamine stress echocardiography showed a positive predictive value of 67% and
      a negative of 70% and identified high and low risk patients. CONCLUSIONS:
      Dobutamine stress echocardiography in patients with acute myocardial infarction
      is a safe and well tolerated test, and provides in a single test useful
      information regarding viability, ischemia and prognosis.

PMID- 8562111
TI  - [The prevalence of the principal cardiovascular risk factors in the population of
      the Azores].
AB  - STUDY OBJECTIVE: to characterize the high mortality rate by ischemic heart
      disease in Azores, by evaluating the main coronary heart disease risk factors
      prevalence in the population. DESIGN: sample study referring the population of 5
      islands: 37 counties. Aleatory choose in the electoral lists. SETTING: the
      selected individuals were convocated by mail to show up at the Hospital for
      evaluation. PATIENTS: 1089 individuals selected by aleatory choose from the
      electoral lists. INTERVENTIONS: the sample was stratified regarding rural (R) and
      urban (U), by sex feminine (F) and masculine (M), age 20-40 and 40 to 60 years
      old. All of them were determined three values of blood pressure, and was taken
      for exact value the medium of the three, inquired the smoking habits and serum
      lipids were determined. We considered risk factors (RF); blood pressure > 140/90
      mmHg, total cholesterol > 200 mg/dl, HDL cholesterol < 35 mg/dl, triglycerides >
      180 mg/dl and smoking habits were stratified in three scores: 1: 1-10, 2: 11-20,
      and 3: more than 20 cigarettes a day. MAIN RESULTS: total prevalences; HBP 20.4%,
      smoking habits 33%, total hypercholesterolemia 47.3%, low HDL cholesterol 17.4%
      and triglycerides 30.5%. CONCLUSIONS: the values found for total cholesterol,
      triglycerides and smoking habits were high and superior to the national medium
      and to those found in reference studies. Preventive strategies are pointed out.

PMID- 8562112
TI  - [Thrombolytic therapy in acute myocardial infarct: the reasons for
      ineligibility].
AB  - STUDY OBJECTIVE: to establish the reasons of ineligibility for thrombolytic
      therapy (TL) in a group of patients with acute myocardial infarction (AMI).
      DESIGN: retrospective analysis of protocols and clinical records. SETTING: the
      medical intensive care unit (ICU) of a tertiary care hospital. PATIENTS AND
      METHODS: we studied the records from patients with AMI admitted to the ICU during
      a five-year period (1987-91) and excluded from TL, to determine the cause(s) of
      ineligibility. RESULTS: we found 1669 patients with AMI, 89 of which were
      excluded from the study. Of the remaining 1580 patients, 1274 (80.6%) did not
      receive TL. Mean age was 64.4 years; 66.4% were men. Mortality was 24.6%. Mean
      duration of chest pain was 19.4 hours. Chief reasons for exclusion from TL were
      advanced age (43.1% of patients) and delayed presentation (55.7%); one of these
      was present in 79.2%. CONCLUSIONS: this study confirmed the high mortality of
      patients with AMI who do not receive TL. Advanced age and delayed presentation
      were the main causes of ineligibility. As age is being abandoned as an exclusion
      criterion, efforts for expansion of TL should center on the earlier arrival of
      patients to centers where it is available.

PMID- 8562113
TI  - [The role of echocardiography in intensive care].
AB  - Echocardiography hasn't played yet a major role in the majority of the noncardiac
      intensive care units, specially the ones with general multi-care profile. In the
      past few years an increasing number of patients admitted have an important
      cardiac component, reason why we emphasize the role of this non invasive
      diagnostic tool. It's easily performed, may be repeated as many times as
      necessary, thus providing a quick diagnosis of the disease, its repercussions and
      medical or surgical interventions.

PMID- 8562115
TI  - [The treatment of obstructive hypertrophic myocardiopathy refractory to medical
      therapy].
AB  - Until a few years ago, therapy of refractory Hypertrophic Obstructive
      cardiomyopathy was mainly surgical--Morrow's myotomy/myectomy or mitral valve
      replacement. Despite the good results of these techniques, they are not free of
      mortality and morbidity. In the last years a new and promising therapy has been
      developed: the Dual Chamber Pacemaker. Technically easier and less invasive than
      surgery, this therapy has achieved better results and lower mortality and
      morbidity during the follow-up.

PMID- 8562114
TI  - [Acute myocardial infarct: apropos a clinical case].
AB  - The AA describe a clinical case of acute myocardial infarction (A.M.I.) with
      prodromal angina and an initial diagnosis based exclusively on clinical criteria;
      the patient was submitted to thrombolysis and had recurrent angina which led to
      the performance of rescue percutaneous coronary angioplasty (P.T.C.A.) that was
      successful. The clinical situations that may precede A.M.I. are discussed and the
      importance of the clinical presentation in its diagnosis are stressed. The
      indications and benefits of rescue P.T.C.A. are also discussed and the AA.
      conclude that the patients with prodromata of A.M.I. must be kept under clinical
      observation, so that prompt necessary therapeutic measures may be undertaken and
      that rescue P.T.C.A. is a therapeutic option of proven clinical benefit.

PMID- 8562116
TI  - Aspects of tricuspid valve disease, heart failure and the "restriction-dilatation
      syndrome".

PMID- 8562117
TI  - Oxidative biotransformation of oxazepam to reactive and nonreactive products in
      rat, mouse and human microsomes.
AB  - 1. The oxidative metabolism of oxazepam by human, B6C3F1 mouse and F344 rat
      microsomes was examined. The major metabolite in all three species was 6-chloro-4
      phenyl-2(1H)-quinazolinecarboxylic acid (CPQ-carboxylic acid). In addition, rat
      microsomes produced 4'-hydroxyoxazepam and oxazepam-dihydrodiol in NADPH
      containing incubations. 2. Covalent protein adducts were increased by the
      addition of NADPH to rat and mouse microsomes but not human microsomes. The
      magnitude of adduct formation was rats > mice > humans. 3. Formation of oxazepam
      dihydrodiol was reduced by the addition of cyclohexene oxide and GSH to the
      incubations. Two additional metabolites were produced under these conditions. One
      of these was tentatively identified as a GSH conjugate. Covalent adduct formation
      was unaffected by GSH or cyclohexene oxide. 4. These results suggest that adduct
      formation occurred via an unknown reactive product rather than via oxazepam
      epoxide, and that the relative rates of oxidative metabolism in vitro parallel
      that in vivo for the three species examined.

PMID- 8562118
TI  - Aluminium deposition in liver and kidney following acute intravenous
      administration of aluminium chloride or citrate in conscious rats.
AB  - 1. Plasma, urinary, liver and kidney cell aluminium (Al) levels were monitored in
      the rat, 1h after intravenous administration of 29630 nmol (800 micrograms) Al as
      either Al chloride or as Al citrate (Al chloride plus excess sodium citrate). Al
      levels were measured in plasma, urine and liver by atomic absorption spectroscopy
      (AAS). Liver and kidney Al content was measured at the cellular and subcellular
      level by electron probe X-ray microanalysis (EPXMA). 2. Urinary excretion of Al
      was significantly higher (P < 0.01), when Al was given as the citrate than as the
      chloride. After 1h, plasma Al levels were significantly lower in the Al citrate
      group than the Al chloride group (59 +/- 3.7 vs 877 +/- 214 nmol ml-1,
      respectively; P < 0.01). 3. Al concentrations were significantly higher in the
      livers of rats receiving Al chloride (818 +/- 252 nmol g-1 wet weight; P < 0.05),
      than in either control or Al citrate groups (122 +/- 41 and 107 +/- 26 nmol g-1
      wet weight, respectively). Al concentrations derived from EPXMA measurements were
      in agreement with AAS values for the three groups, with significantly higher Al
      concentrations in the Al chloride group (1.7 +/- 0.4 nmol mg-1 dry weight; P <
      0.05) than in the control or Al citrate groups, where Al was not detectable.
      EPXMA analysis showed that Al was distributed in all liver organelles analysed
      (cytoplasm, mitochondria, nucleus, ER) and was not preferentially taken up by any
      one organelle in Al chloride treated rats. 4. Significant amounts of Al were
      found in cytoplasm and mitochondria of proximal tubule cells of rats given Al
      citrate (0.64 +/- 0.15 and 0.80 +/- 0.11 nmol mg-1 dry weight, respectively), but
      not in nuclei or lysosomes of these cells. Al levels were not detectable in
      control kidneys, in proximal tubule cells after Al chloride administration or
      distal tubule cells after either Al treatment.

PMID- 8562119
TI  - Effect of urinary alkalinisation and acidification on the tissue distribution of
      hexachlorophene in rats.
AB  - 1. Urinary alkalinisation may be helpful in treating acute poisoning with
      uncouplers of oxidative phosphorylation containing a phenolic hydroxyl (pKa 4-6)
      or other acidic moiety. 2. We studied the effects of urine alkalinisation and
      acidification on the tissue distribution of hexachlorophene (HCP, pKa 5.7) in
      male Sprague Dawley rats (10 rats/group). 3. Ammonium chloride (10 mL kg-1, 2%
      m/v) or sodium bicarbonate (10 mL kg-1, 2% m/v) were administered by gavage on
      three occasions over 24 h, prior to a single gavage dose of HCP (180 mg kg-1).
      Controls received aqueous sodium chloride (10 mL kg-1, 0.9% m/v) followed by
      either HCP (180 mg kg-1) or vehicle alone. 4. Urine pH, body mass and body
      temperature were monitored during the study and, at the conclusion of the
      experiment (12 h post-HCP dose), organ mass (liver, kidney, brain), and plasma,
      urine and tissue HCP concentrations were measured. 5. No clinical features of
      toxicity were observed in any group. However, sodium bicarbonate significantly
      reduced median HCP in liver--median plasma and kidney HCP concentrations were
      also reduced but not significantly. Conversely, ammonium chloride significantly
      increased median HCP concentrations in liver and kidney--median plasma HCP was
      also increased but not significantly. 6. The results provide some support for the
      hypothesis that blood pH influences the tissue distribution of uncouplers of
      oxidative phosphorylation containing an acidic moiety. Urinary alkalinisation may
      be useful in treating acute poisoning with these compounds.

PMID- 8562120
TI  - Dietary effect on mixed function P450 1A2 activity assayed by estimation of
      caffeine metabolism in man.
AB  - Two studies were performed in order to evaluate cytochrome P450 1A2 mediated
      caffeine metabolism during different nutritional conditions. 1. In the first
      study, 23 healthy male non-smokers, mean age 25, changed from a customary mixed
      diet to a standard diet in 6 days. The 6 day's standard diet was based on bread,
      potatoes, rice and boiled meat. Thus, broccoli, cabbage and other cruciferous
      vegetables, spinach, leeks, onion, parsley, grapefruit, toasted bread, fried and
      charcoal grilled food, smoked fish and meat, ham and sausages were avoided. 2. In
      the second study, 33 healthy non-smoking subjects, 24 men and nine women mean age
      25 years, volunteered. The study was designed to compare a customary home dietary
      period with the 6 day period of low dietary P450 induction and with a 5 day
      supplementary dietary period, i.e. ingestion of known dietary inducers. None of
      the women were using oral contraceptives or were pregnant during the experimental
      period. In the period of diet supplementation, the volunteers received charcoal
      grilled hamburger as a supplement to the standard low induction diet for lunch
      for 5 days. The hamburgers were made with 150 g beef (18-20% fat) and were
      grilled on charcoal for 10 min on each side until they were 'well done'. In the
      present study P450 1A2 activity was estimated from the caffeine metabolic ratio,
      the so-called CYP 1A2 index:(AFMU + 1-MX + 1-MU/ 17 -DMU) of the caffeine
      metabolites formed after oral ingestion of 200 mg caffeine. Urine was collected 4
      8 h after caffeine ingestion in study 1 and 5 h after caffeine ingestion in study
      2. In study 1 the CYP 1A2 index decreased from 4.28 +/- 0.98 in the customary
      home dietary period to 3.87 +/- 0.69 in the standard dietary period corresponding
      to 10.6% (P < 0.06) decrease in the CYP 1A2 index. In study 2 the CYP 1A2 index
      decreased from 4.47 +/- 1.76 in the customary home dietary period to 3.90 +/-
      1.12 in the standard dietary period corresponding to a 14.6% decrease (P < 0.2)
      in P450 1A2 activity. The female subjects had a mean index value of 3.89 +/- 1.14
      which was 16.8% (P = 0.09) lower than the mean male index value of 4.68 +/- 1.76
      during the home dietary period. After the 5 day period with charcoal grilled
      hamburgers as a dietary supplement, the CYP 1A2 index increased to almost the
      same level as in the customary home dietary period. The index increased to 4.45
      +/- 1.57 in the whole group of volunteers, corresponding to a 14.1% (P < 0.05)
      increase. The mean increase in the CYP 1A2 index covered a large inter-individual
      variation in response to ingestion of charcoal grilled meat ranging from a 29%
      decrease to a 147% increase.

PMID- 8562121
TI  - Mortality due to poisoning in a developing agricultural country: trends over 20
      years.
AB  - The cause of death as recorded in 37,125 death certificates (DCs) issued in the
      Kandy District over 20 years at 5-year intervals beginning in 1967 were analysed
      to determine the trends in mortality caused by poisoning in the community.
      Poisoning accounted for 718 (19.3 per 1000) deaths, the highest number being in
      the third decade of life (41.9%). Male:female ratio was 3:1. The agent
      responsible for 77% of the deaths was pesticides. Acids and chemicals accounted
      for 6.9% of the deaths. Other poisons each contributing to less than 1% of the
      deaths were: plant poisons, food items, drugs, kerosine oil and alcohol. Nearly
      half the deaths had occurred outside the town area, at home or in small hospitals
      in the periphery. Mortality due to poisoning showed an increasing trend during
      the 20 years, from 11.8 to 43/1000 deaths, and this increase was most marked in
      the periphery, from 8/1000 to 70/1000. This increase paralleled the increase in
      suicide figures in the country. Our findings call for a shift in emphasis in
      public education towards first-aid management of intoxication. Health services of
      developing countries should provide appropriate resuscitative equipment, and
      ensure a regular supply of antidotes and other medication to all rural hospitals.
      Management of pesticide poisoning should be emphasised in the curricula for
      medical graduates, nurses, and paramedics.

PMID- 8562122
TI  - Testing human hair for carbamazepine in epileptic patients: is hair investigation
      suitable for drug monitoring?
AB  - Hair samples were obtained from 30 patients who had been taking carbamazepine in
      fixed daily doses for more than 6 months. Carbamazepine was extracted from the
      hair by enzymatic hydrolysis and quantified by gas chromatography-mass
      spectrometry. Concentrations ranged from 1.2 to 57.4 ng mg-1. The concentrations
      of carbamazepine were significantly correlated (P < 0.0001) with the daily dose
      and the correlation coefficient was 0.793. Although it had been suggested by
      several authors that the measurement of carbamazepine in hair might provide a
      better index of individual dosage history than the plasma level assays, the
      deviations observed in this study led to the conclusion that hair samples are not
      suitable for evaluating the quantity of drug consumed. However, hair testing may
      be useful for documenting clinical disorders by sectioning the shaft into
      segments corresponding to 1 month periods.

PMID- 8562123
TI  - Sensitivity of rapid radiological screening in lead poisoning for traditional
      medicines.

PMID- 8562124
TI  - Drugs and Chemicals--Risks and Benefits. Joint meeting of the Finnish Society of
      Toxicology and the Finnish Pharmacological Society. 31 March-1 April, 1995.
      Abstracts.

PMID- 8562125
TI  - An overview of the symposium on 'Peroxisomes: biology and role in toxicology and
      disease', Aspen, Colorado, USA, June 28-July 2 1995.

PMID- 8562126
TI  - A knockout for risk assessment.

PMID- 8562127
TI  - Do fruit juices stimulate iron absorption and toxicity?

PMID- 8562128
TI  - A tricky route from fins to legs for CYP nomenclature.

PMID- 8562129
TI  - A whiff of new interest in alkane evolution.

PMID- 8562130
TI  - The Merkel cell: recent findings and unresolved problems.
AB  - Recently acquired knowledge about the Merkel cell is reviewed, and unresolved
      problems on the development and function of the cell are discussed. Concerning
      its developmental origin, the epidermal origin hypothesis has become prevalent
      since the discovery of cytokeratin polypeptides in it. While the significance of
      this cell is still unclear, the following functions are presumed: 1) the release
      of neurotransmitters or neuromodulators to the SAI mechanosensory nerve
      terminals; 2) the attraction and trophic action on peripheral nerve fibers; 3)
      the stimulation of the proliferation of keratinocytes leading to the three
      dimensional development of the epidermal anlagen; 4) the maintenance of the
      normal differentiation of keratinocytes; and 5) the release of bioactive
      substances to subepidermal structures. These multiple functions imply a
      possibility that one Merkel cell sequentially performs all these different roles
      during its life span. However, it is also possible that Merkel cells consist of
      several functionally different subpopulations.

PMID- 8562131
TI  - On the real structure of the cytoplasmic matrix: learning from the embedment-free
      electron microscopy.
AB  - The recent debate on the nature of the cytoplasmic matrix is reviewed on the
      basis of results obtained by electron microscopy of embedment-free materials,
      i.e., the critical point-dried whole mount-cell method, the polyethylene glycol
      (PEG)-embedding and subsequent de-embedding section method, and the freeze
      etching method. Fine structural images obtained by these methods are carefully
      evaluated and close correspondence with electron microscopy regardless of these
      methods is demonstrated. Especially, 'novel' filamentous structures--the
      microtrabecular strands and the cross-linkers--correspond well to each other;
      they are structures which have been included in epoxy sections by conventional
      methods, but have been obscured simply because of a similar property of electron
      scattering between the filamentous structures and epoxy resin. Although this
      correspondence seems to support the existence of the microtrabeculae, the
      electron microscopy of serum albumin, when processed by the PEG-method, also
      exhibits filamentous networks resembling the microtrabecular lattice. This,
      together with the finding on the centrifugation of in situ cells, strongly
      suggests a possibility that most, if not all, microtrabecular strands and cross
      linkers in cells without pretreatment by detergents do not represent actual in
      situ structures.

PMID- 8562132
TI  - Age changes in cerebellar oligodendrocytes: the appearance of nuclear filaments
      and increase in the volume density of the nucleus and in the number of dark cell
      forms.
AB  - A qualitative and quantitative ultrastructural study (volume density of the
      nucleus and cell countings) on age-related changes occurring in neocerebellar
      oligodendrocytes of the granular layer was carried out in female albino rats aged
      2-24 months. Taking into account the cytological features, two types of
      oligodendrocytes could be discerned, designated as Type I and Type II.
      Observations showed that, from 18 months onwards, the appearance of bundles of
      nuclear filaments running throughout the euchromatin areas are common occurrence
      in Type II oligodendrocytes. The lowest and highest mean volume density of the
      nucleus is achieved, respectively, at 2 months (50.67%) and at 21 months
      (64.93%); the analysis of variance of the parameter with ageing displays a most
      statistically significant result. There is also a positive and linear correlation
      between the volume density and age. The percentage of Type I oligodendrocytes
      (out of the total of counted oligodendrocytes) predominates from 2 to 15 months;
      after being even at 18 months, the percentage of Type II oligodendrocytes
      preponderates at 21 and 24 months. Although oligodendrocytes are capable of
      undergoing mitosis, it is concluded that they are prone to morphological changes
      with ageing, a warning that the physiology of oligodendrocytes may be eventually
      affected.

PMID- 8562133
TI  - Depletion of thymic macrophages in the rat by liposome-encapsulated
      dichloromethylene diphosphonate.
AB  - Liposome-entrapped dichloromethylene diphosphonate (Cl2MDP) was injected locally
      into the thymus of adult rats. This treatment, which has been found to deplete
      resident macrophages in other organs, also reduced the number of thymic
      macrophages. The depletion was evident in the cortex and the corticomedullary
      zone at 5, 13 and 23 days after Cl2MDP treatment, while the decrease in medullary
      macrophages only became significant 13 and 23 days after injection. However, the
      maximal reduction of macrophages was evident 13 days after this treatment. Thirty
      five days after Cl2MDP treatment, macrophages repopulated the thymus. Our results
      suggest that the cortical and cortico-medullary macrophages have a high
      phagocytic activity consistent with their predominant role as scavengers of the
      large numbers of thymocytes that die under physiological conditions. It is
      concluded that liposome-mediated depletion of thymic macrophages can serve as an
      experimental model to study the roles of these cells.

PMID- 8562134
TI  - The main excretory duct (Stensen's) of the human parotid gland: a transmission
      and scanning electron microscope study.
AB  - The epithelial cells of the human parotid main excretory duct (Stensen) were
      studied by transmission (TEM) and scanning (SEM) electron microscopy through a
      variety of procedures that allowed the visualization of their three-dimensional
      microanatomy. Stensen's duct in humans is lined, in its distal portion, with a
      pseudostratified epithelium with tall principal cells and smaller basal cells,
      while the epithelium becomes progressively stratified cylindrically toward the
      oral stoma. Goblet cells are scattered among the other epithelial cells. The
      principal cells exhibit, on their lateral surfaces, numerous flattened laminar
      folds probably involved in transporting processes. A well-developed smooth
      endoplasmic reticulum intermingled with mitochondria occupies the cellular
      apices. Some vesicles are recognized on the cytoplasmic surfaces of the apical
      and lateral plasmalemma when cytoplasmic organelles are removed. All these
      features are interpreted as being involved in the process of endocytosis. In both
      TEM and SEM, the principal cells show a relevant number of irregular apical
      protrusions that may represent a kind of apocrine secretion. Thus, with regard to
      function, the human Stensen's duct seems to modify the composition of saliva by
      processes of resorption and secretion, the latter coming from goblet cells as
      well. The basal cells have a surface microanatomy completely different from that
      of principal cells. They exhibit, in fact, only sparse microvillosities and
      smooth areas on their lateral aspect, while their stromal surface is greatly
      augmented by irregular thin ramified processes. The role of basal cells is also
      discussed.

PMID- 8562135
TI  - Intraepithelial nerve fibers in the nasal mucosa of the rat with special
      reference to the localization of CGRP, VIP and nitric oxide (NO).
AB  - Previous studies have demonstrated that the epithelium of the respiratory portion
      of rat nasal mucosa is amply supplied by nerve fibers with immunoreactivities for
      calcitonin gene-related peptide (CGRP) and substance P (SP), these fibers most
      likely acting as sensory mediators in the mucosa. The present study demonstrates
      that some intraepithelial fibers contain a VIP-immunoreactivity whose occurrence
      in these nerves has previously been neglected. The present study further aims to
      confirm the occurrence of NO-producing intraepithelial nerve fibers in the rat
      nasal mucosa and to examine its colocalization with CGRP and with VIP. Double
      staining methods were used to evaluate the colocalization of NADPH-diaphorase.
      The reactivity for NADPH-diaphorase and that for CGRP coexisted in only a small
      part, if any, of the nerve fibers distributed at the basal portion of the
      epithelium. In the perpendicularly and obliquely oriented transepithelial nerve
      fibers, both reactivities were clearly demonstrated to be separated in different
      fibers. VIP immunoreactivity was also present in a part of the intraepithelial
      nerve fibers of the nasal mucosa, and their entire population was shown to be
      positive for NADPH-diaphorase. The NADPH-diaphorase-positive reaction was
      displayed in only a small population of neurons in the trigeminal ganglion,
      whereas it was seen in numerous neurons in sphenopalatine ganglion, being
      colocalized with VIP.

PMID- 8562136
TI  - A histological study of the cardiac muscle of the human superior and inferior
      venae cavae.
AB  - Human superior and inferior venae cavae at the orifices to hearts obtained from
      two cadavers were histologically examined with regard to the distribution of
      cardiac muscle fibers in their walls. The superior vena cava contained cardiac
      muscle fibers together with smooth muscle fibers. The cardiac muscle fibers were
      distributed uninterruptedly from the atrium to the root of the azygos vein,
      covering a length of 45 mm. Cardiac myocytes were present outside the smooth
      muscle and coursed in bundles longitudinally, obliquely, or circularly. Cardiac
      myocytes occupied one to two thirds of the wall thickness, but decreased in
      amount toward the periphery. The inferior vena cava also contained both cardiac
      and smooth muscle fibers. The cardiac muscle fibers extended continuously,
      covering a distance of 18 mm from the atrium to a level just under the diaphragm.
      Their fibers were bundled, running circularly or obliquely, and being more
      abundant in the anterior wall than in the posterior. From these findings, the
      venae cavae close to the atrium are histologically regarded as an extension of
      the atrium. The venae cavae close to the atrium probably contract together with
      the atrium and work as a functional valve that contributes to the pumping
      mechanism of the heart.

PMID- 8562137
TI  - Three-dimensional organization of lymphatics in the dog small intestine: a
      scanning electron microscopic study on corrosion casts.
AB  - Casts of the lymphatics of the canine small intestine were made by direct
      injection of a low viscosity methacrylate resin into a large lymphatic in the
      submucosal layer, and observed under a scanning electron microscope. The
      lymphatics started with rod-like central lacteals in the villi of the jejunum and
      leaf-like ones in those of the ileum. The bases of the lacteals were connected by
      slender lymphatics forming a three-dimensional network, tentatively called the
      "superficial lamina propria lymphatic plexus". From this plexus, a few straight
      branches descended through the lamina propria to drain into a well developed
      "deep lamina propria lymphatic plexus", which was extended two-dimensionally
      closely above the lamina muscularis mucosae. From this plexus, a few short
      lymphatics extended and penetrated the muscularis mucosae and drained into the
      "superficial submucosal lymphatic plexus", a coarse mesh work of thick
      lymphatics. From this plexus, a few slender lymphatics descended to drain into a
      second lymphatic plexus, called the "deep submucosal lymphatic plexus", which
      extended two-dimensionally on the circular muscle layer. This deep submucosal
      plexus was a coarse network of thick knotty lymphatics. A large collecting
      lymphatic was occasionally seen running through the mesh. The tunica muscularis
      contained tubular lymphatics extending horizontally parallel to the muscle fiber,
      both circular and longitudinal.

PMID- 8562138
TI  - The occurrence of acidic fibroblast growth factor-like immunoreactivity in
      subpopulations of endocrine cells in the pancreas and intestine of the rat.
AB  - A study of the immunocytochemical localization of acidic fibroblast growth factor
      (aFGF) in the rat digestive system using a polyclonal anti-aFGF antiserum
      revealed immunoreactive cells in the periphery of the islets of Langerhans and in
      the mucosal epithelia of the intestine, from the jejunum through the colon. In
      the pancreatic islet, light microscopic immunostaining of consecutive sections
      with anti-aFGF and anti-glucagon antisera as well as pre-embedding immuno
      electron microscopy demonstrated that a FGF-like immunoreactivity belongs to the
      A cell. In the intestinal epithelium, the aFGF-immunoreactive cell was
      simultaneously reactive to anti-glucagon antiserum and was ultrastructurally
      identified as the L-cell, which is known to produce glucagon-like immunoreactants
      derived from proglucagon. Post-embedding immuno-electron microscopy further
      revealed that the immunoreactivity is localized in the secretory granules of A-
      and L-cells. These results suggest that an aFGF-like immunoreactant occurs in the
      populations of gastro-entero-pancreatic endocrine cells that express proglucagon.

PMID- 8562139
TI  - Strongly anionic sites in peripheral axons of the rat sciatic nerve: light and
      electron microscopic detection using cationic colloidal iron.
AB  - Anionic sites in the rat sciatic nerve were studied by light and electron
      microscopy using a fine-granular cationic colloidal iron staining method
      (Murakami et al., 1986). The axon, as well as the endoneurium, the epineurium and
      the basement membrane of Schwann cells, were all confirmed to react strongly to
      the cationic colloidal iron even at a pH value of 1.0-2.0. Prior hyaluronidase
      digestion decreased the colloidal strain of the epineurium; chondroitinase ABC
      weakened that of the endoneurium and the basement membrane of Schwann cells.
      However, as axons retained stainability with cationic colloidal iron even after
      combined digestion with hyaluronidase, chondroitinase ABC, heparitinase and
      keratanase, the authors consider sulfated glycoconjugates and not those
      substances which are digestible with such common enzymes. The acid groups ionized
      at pH 1.0 are most likely sulfate groups. Methylation deprived the axon of the
      reactivity to cationic colloidal iron staining, and even subsequent
      saponification could not recover this reactivity to its full extent. In the axon,
      electron microscopy revealed a deposition of colloidal iron on the external
      surfaces of microtubules and neurofilaments in the axoplasm and of very fine
      filaments connecting them. This highly negatively charged intra-axonal network
      could also serve toward a supportive function in maintaining the spatial
      distribution of microtubules either mechanically or through electrostatic
      repulsion or, possibly, serve as an intra-axona cation exchange reservoir.

PMID- 8562140
TI  - Who shall decide?

PMID- 8562141
TI  - Thymidylate synthase inhibition, a dead end?

PMID- 8562142
TI  - A proposal for a new approach to intergroup cancer trials.
AB  - Currently, North American intergroup trials are conducted according to the
      Intergroup Guidelines, which require that a lead group take responsibility for
      data management. Intergroup studies conducted in this manner have been very
      successful in rapidly accruing large numbers of patients to trials addressing
      significant questions, but it has been difficult for group statistical centres to
      cope with the resultant peaks in data flow. Our groups recently succeeded in
      combining the data from three independently designed and conducted trials to
      carry out a planned pooled analysis. This experience has led us to employ the
      same approach to data management in designing a forthcoming intergroup trial. We
      will use a common protocol and capture the same data elements on our forms, but
      each group will be responsible for the collection and quality control of its own
      data. A common data set will be created and updated periodically during the
      study, and will be used for the final analysis. We suggest that this model has
      advantages over the current approach to data management on intergroup trials, but
      still retains the features which distinguish an intergroup study from meta
      analysis.

PMID- 8562143
TI  - Can positron emission tomography (PET) be used to detect subclinical response to
      cancer therapy? The EC PET Oncology Concerted Action and the EORTC PET Study
      Group.
AB  - At the EORTC NCI New Drug Development Meeting in Amsterdam in 1994, a workshop,
      suggested by the EC PET (positron emission tomography) Oncology concerted action,
      was held to bring together many of those European PET centres investigating the
      use of [18F]FDG ([18F]2-fluoro-2 deoxyglucose) PET scanning as a measure of
      response to cancer therapy. Of the current 31 PET centres in Europe invited to
      contribute, 15 centres already had data and others expressed interest. Many of
      the groups were collaborating with local oncologists to measure tumour response
      to chemotherapy (12 groups) and radiotherapy (three groups) with this technique.
      Despite variations of methodology, and difficulties in data interpretation,
      assessment of tumour [18F]FDG uptake was thought to be a reasonable method for
      the functional imaging of tumours, assessing metabolic rate and providing a
      measure of tumour response. Broadly, pooling experience, it would appear that
      changes in [18F]FDG tumour uptake following one or two cycles of chemotherapy
      treatment was related to ultimate clinical responses. Patients showing most
      reduction in [18F]FDG uptake achieved the best clinical responses. Data were also
      available on the effect of chemotherapy on normal tissues and some data on the
      effect of radiotherapy and tumour response. It was concluded that changes in
      [18F]FDG uptake as measured with PET may provide useful information on clinical
      as well as subclinical response of tumours to anticancer therapy. This could be
      useful as a guide to early response to therapy as well as providing functional
      assessment of residual masses of disease. More specific markers of cellular
      proliferation e.g. [11C]thymidine, or [11C]- amino acids may provide even more
      accurate information. A strategy was outlined whereby PET scanning protocols
      could parallel EORTC early clinical trials so that [18F]FDG response information
      could supplement phase I and II clinical studies. Following these developments,
      an EORTC study group was formed under the auspices of the EORTC research branch,
      and the strategy for future development in Europe outlined.

PMID- 8562144
TI  - Re-evaluation of the molecular pharmacology of mitomycin C.

PMID- 8562145
TI  - Randomised consent designs in cancer clinical trials.
AB  - In 1977, Zelen proposed a new design for clinical trials with the aim of
      increasing recruitment by avoiding some of the problems associated with obtaining
      informed consent. These 'randomised consent' designs have proved controversial,
      and have not often been used. This paper explains the statistical aspects of
      single and double randomised consent designs and reviews some of the ethical
      issues. All identified published cancer treatment trials using a randomised
      consent design are considered in some detail. Reasons for and against the use of
      these designs are summarised.

PMID- 8562146
TI  - 'Tomudex' (ZD1694): results of a randomised trial in advanced colorectal cancer
      demonstrate efficacy and reduced mucositis and leucopenia. The 'Tomudex'
      Colorectal Cancer Study Group.
AB  - 'Tomudex' (ZD1694), a direct and specific thymidylate synthase (TS) inhibitor
      entered phase III studies in November 1993. We present here the first analysis of
      a randomised multicentre, international phase III study. 439 patients with
      previously untreated advanced colorectal cancer were randomised to Tomudex 3.0
      mg/m2 given once every 3 weeks or 5-fluorouracil (5-FU) 425 mg/m2 and leucovorin
      (LV) 20 mg/m2 for 5 days (the Mayo regimen), given every 4-5 weeks. Patients were
      evaluated weekly for toxicity and every 12 weeks for objective response. The two
      groups were well matched in terms of demographic characteristics. The mean age of
      the patients was 61 years and most had either liver (78%) or lung (25-29%)
      metastases. Ninety seven per cent of patients allocated to Tomudex and 94% of
      those allocated to 5-FU plus LV had measurable disease. Response was assessed
      using WHO/UICC criteria; all response data were source validated; 19.8% of
      patients who received Tomudex and 12.7% of patients who received 5-FU plus LV had
      complete or partial responses (P = 0.059, odds ratio 1.7, 95% confidence limits
      0.98-2.81). There were no statistically significant differences in time to
      progression or survival between the two groups. Patients who received Tomudex
      spent a substantially shorter time in hospital for dosing and had significantly
      lower rates of grade 3 and 4 toxicities such as leucopenia and mucositis.
      Patients who received Tomudex had a significantly higher incidence of reversible
      grade 3 or 4 increase in transaminases, which appear to be of limited clinical
      significance. Improvement in quality of life, weight gain and performance status
      was seen in both groups. Tomudex has benefits in terms of higher response rates,
      reduced toxicity and more frequent palliative benefits when compared with 5-FU
      plus LV in the management of advanced colorectal cancer, and has a more
      convenient administration schedule.

PMID- 8562148
TI  - Male breast cancer: results of the treatments and prognostic factors in 397
      cases.
AB  - From 1960 to 1986, 397 cases of non-metastatic male breast cancer (MBC) treated
      in 14 French regional cancer centres were reviewed. The median age was 64 years
      (range 25-93). TNM classification (UICC, 1978) showed seven T0, 79 T1, 162 T2, 31
      T3, 74 T4 and 44 unclassified tumours (Tx). Clinical positive lymph nodes were
      found in 31% of the patients. 24 patients received radiotherapy only, and 373
      underwent surgery, 247 of these with postoperative irradiation. Adjuvant
      chemotherapy and hormonal therapy were used in 71 and 68 patients, respectively.
      There were 382 infiltrating carcinomas and 15 pure ductal carcinoma in situ.
      Lymph node involvement was found in 56% of infiltrating carcinoma. The oestrogen
      (ER) and progesterone (PgR) receptors were positive in 79% and 77%, respectively,
      of examined cases. Isolated local and regional recurrence were observed in 8.8%
      and 4.5% of cases, respectively and 40% of patients developed metastases. The
      crude survival rates by Kaplan-Meier method were 65% and 38% at 5 and 10 years,
      respectively, and the disease-specific survival rates (without death due to
      intercurrent disease or second cancer) was 74% at 5 years and 51% at 10 years.
      The disease-specific survival rate for pN- and pN+ groups were 77% and 39% at 10
      years. The prognostic factors were clinical size (T) and histological axillary
      status (pN-/pN+). The relative risk of death for pN- was 1.0, 2.0 and 3.2 in the
      T0-T1, T2 and T3-T4 groups, respectively. For pN+, these relative risks increased
      1.9, 3.9 and 6.0 in the same groups. The optimal treatment include modified
      radical mastectomy and irradiation for cases with risk factors of local relapse
      (nodal invasion, large tumour with cutaneous or muscular involvement).
      Locoregional failure had unfavourable prognosis. First-line adjuvant treatment
      seems to be tamoxifen, due to the very high rate of positive hormonal receptors
      and the old age of the patients, which contraindicate chemotherapy in many cases.
      The prognosis of patients with breast cancer is the same in male and female
      patients when disease-specific survival rate, tumour size and axillary
      involvement are compared.

PMID- 8562147
TI  - Cancer patients, doctors and nurses vary in their willingness to undertake cancer
      chemotherapy.
AB  - Cancer patients' attitude to chemotherapy were compared with those of doctors,
      nurses and healthy controls. 98 cancer patients, 42 healthy subjects, 44
      oncologists, 35 surgeons, 32 oncology nurses and 70 surgical nurses received a
      questionnaire presenting a hypothetical situation involving a toxic chemotherapy
      regimen. Each were asked to indicate the minimal benefit with respect to chance
      of cure, life prolongation and symptom relief they would demand to accept the
      treatment. The patients and the surgical nurses were most reluctant with regard
      to the treatment. The subgroup of patients under 50 years which matched the
      oncologists, surgeons and controls with respect to age, cohabitant status and
      children were significantly more willing to accept the regimen than the controls
      and professional groups. Patients under 40 years would accept the toxic treatment
      with hardly any benefit as chance of cure (7%, median), life prolongation (3
      months) and symptom relief (8%). Among the professionals, oncologists were most
      willing to accept therapy, whereas surgical nurses and surgeons were least
      willing.

PMID- 8562149
TI  - The prognostic significance of the axillary apex biopsy in clinically operable
      breast cancer.
AB  - To evaluate the prognostic significance of the axillary apex biopsy and its
      impact on clinical practice, a retrospective analysis was performed in 875
      patients with clinically operable breast cancer who underwent this procedure from
      1977 to 1985 (165 TNM stage I; 512 TNM stage II; 198 TNM stage IIIA). Apex biopsy
      is performed as a staging procedure. Apex biopsy positive patients are treated by
      radiotherapy alone, while apex biopsy negative patients are treated with breast
      conserving therapy or mastectomy, both including complete axillary dissection.
      The apex biopsy was tumour positive in 4% of TNM stage I patients; 17% of stage
      II patients and 40% of stage IIIA patients. Among patients with clinically node
      negative disease, the apex biopsy was positive in 12%; in patients with palpable
      suspected lymph nodes this figure was 45%. Actuarial 8 y survival rates for
      patients with stage I, II and III disease and a negative apex biopsy were 83, 70
      and 50%, respectively. The corresponding figures for patients with a positive
      apex biopsy were 60, 28 and 14%. In a multivariate analysis, a positive apex
      biopsy, clinical N classification and T classification were independent
      prognostic factors for survival (P < 0.0001). We conclude that a positive apex
      biopsy is rare in clinical stage I breast cancer, and that in patients with TNM
      stage II and III disease the procedure is an important tool to assess prognosis
      pre-operatively.

PMID- 8562150
TI  - Breast tumour response to primary chemotherapy predicts local and distant control
      as well as survival.
AB  - The purpose of the present paper was to evaluate correlations between clinical
      response to chemotherapy and outcome in a subgroup analysis of premenopausal
      patients with tumours considered too large for breast conserving surgery, treated
      with primary chemotherapy (n = 200) from a previously published trial (Scholl
      S.M., Fourquet A., Asselain B, et al. Eur J Cancer 1994, 30A, 645-652). Objective
      response rates amounted to 65% following four courses. In a multivariate Cox
      regression analysis, comparing seven parameters, the following variables were
      associated with poor survival: clinically involved nodes [N1b:RR: 2.7 (95% CI 1.3
      5.3)], the failure to respond to chemotherapy [D:RR: 2.62 (95% CI 1.3-5)] and a
      raised S phase fraction [SPF > 5%: RR: 2.4 (95% CI 1.2-5)]. Parameters associated
      with increased metastatic recurrence rates, by order of entry in the model, were:
      young age [< 35: RR: 2.46 (95% CI 1.2-5)], large clinical tumour size [T3: RR:
      2.02 (95% CI 1.2-3.4)], poor histological grade (SBR III: RR: 1.93 (95% CI 1.1
      3.3)] and the failure to respond to chemotherapy [D: RR: 1.91 (95% CI 1-3.4)].
      The assessment of both tumour cell proliferation rates as well as possibly drug
      resistance markers (although not available in the present study) should be
      helpful in selecting patients likely to benefit from intensified chemotherapy
      regimens. The most accurate predictor of response in the present study appeared
      to be the response to chemotherapy treatment itself.

PMID- 8562151
TI  - Pamidronate infusions as single-agent therapy for bone metastases: a phase II
      trial in patients with breast cancer.
AB  - Pamidronate is a potent biphosphonate which modulates tumour-induced osteolysis
      (TIO) by inhibiting osteoclast-mediated bone resorption. In a phase II trial, 69
      breast cancer patients with symptomatic progressive bone metastases were given
      infusions of pamidronate 60 mg over 1 or 4 h every 2 weeks for a maximum of 13
      infusions or until progressive disease (PD) at any site. No other systemic
      anticancer therapy was allowed. Pain was measured using a visual analogue scale,
      mobility using a detailed eight-point questionnaire and analgesic intake using a
      six-point scale. Improvements in pain, mobility and analgesic scores occurred in
      61, 50 and 30% of patients, respectively, with 33, 21 and 16% achieving a 40%
      improvement for > or = 8 weeks. At trial discontinuation, baseline levels of pain
      and mobility had improved by 27% (P = 0.001) and 20% (P = 0.004), respectively,
      despite a one category reduction in analgesic intake in 27% of patients. Using
      this relatively high dose of pamidronate, symptomatic response was independent of
      the number of bone metastases and also of infusion rate. The infusions were well
      tolerated with no major toxicities reported. Pamidronate infusions provide useful
      palliation for breast cancer patients with symptomatic bone metastases.

PMID- 8562152
TI  - Combined intraperitoneal plus intravenous chemotherapy after curative resection
      for colonic adenocarcinoma.
AB  - Patients who underwent potential curative surgery for colonic adenocarcinoma were
      enrolled in a prospectively randomised, controlled clinical trial of combined
      intraperitoneal (i.p.) plus systemic intravenous (i.v.) chemotherapy with 5
      fluorouracil (5-FU) and leucovorin (LV). We investigated whether this adjuvant
      treatment approach, specifically addressing the risk of peritoneal and hepatic
      recurrence, could improve disease-free and overall survival. Between May 1988 and
      December 1990, 121 patients with resected stage III or high-risk stage II
      (T4N0M0) colon cancer were randomly assigned for observation (which was
      considered standard care until the NIH consensus conference) or adjuvant
      chemotherapy with LV (200 mg/m2) plus 5-FU (350 mg/m2), both given i.v. (days 1
      4) and i.p. (days 1 and 3) every 4 weeks for a total of six courses. After a
      median follow-up time of 4.6 years, a comparative analysis between the two groups
      of patients suggested both an improvement in disease-free survival (75% versus
      58%; P = 0.06) and a survival advantage (78% versus 63%; P = 0.05) in favour of
      adjuvant chemotherapy. The sites of recurrence were also different, i.e. local
      regional and intrahepatic tumour recurrences were observed in only 6/58 (10%) and
      5/58 (9%) adjuvant treated patients as compared to 11/60 (18%) and 10/60 (17%)
      observed patients. The overall benefit of adjuvant therapy appeared to be
      greatest in patients with stage III colon cancer. Treatment-associated toxicity
      was infrequent and generally mild with only 5% experiencing severe (WHO grade 3)
      adverse reactions. Interim results of this adjuvant trial suggest that combined
      i.p. plus systemic i.v. chemotherapy with 5-FU and LV represents a potentially
      effective adjuvant regimen in stage II/III colon cancer.

PMID- 8562153
TI  - Very high-dose chemotherapy with autologous peripheral stem cell support in
      advanced ovarian cancer.
AB  - 20 patients with stage III-IV ovarian cancer were submitted to induction
      chemotherapy (ICT) (40 mg/m2 cisplatin, days 1-4; 1.5 g/m2 cyclophosphamide, day
      4; every 4 weeks for 2 cycles) followed by intensified CT (100 mg/m2 cisplatin,
      day 1; 650 mg/m2 etoposide, day 2; 1.8 g/m2 carboplatin by 24 h infusion, day 3).
      Haematological support consisted of autologous peripheral stem cells (APSC) and
      bone marrow (ABM) transplant (T) in 16 and 4 patients, respectively. All patients
      were evaluable for toxicity and 19 for pathological response (PR), one patient
      dying of systemic mycosis after ABMT. Severe (grade 3-4) non-haematological toxic
      effects were gastrointestinal (100%), neurological (10%) and hepatic (10%). PR
      was observed in 84% of patients (complete response 37%, partial response with
      microscopic residual disease 26%, partial response with macroscopic residual
      disease 21%). Five year overall survival was 60% and progression-free survival
      was 51% with 9 patients still disease-free (DFS). APSCT significantly reduced the
      duration of aplasia compared with ABMT, and toxicity was acceptable in those
      patients undergoing APSCT. The prolonged DFS in patients showing PCR suggests
      that this new approach may have a therapeutic impact.

PMID- 8562154
TI  - An analysis of approaches to the treatment of endometrial cancer in western
      Europe: a CTF study.
AB  - The role of this research is to define the clinical-therapeutic approach to
      endometrial cancer currently being followed in some of the most important centres
      of reference for gynaecological cancer in Western Europe. Data was collected by
      means of a questionnaire, concerning specific diagnostic and therapeutic options,
      sent to 115 leading centres for gynaecological oncology in Western Europe, and 82
      responses were received. The analysis of the management of this neoplasia in
      Western European countries shows significant differences regarding some
      particular clinical conditions. Only 24.4% of the interviewed centres stated that
      they perform lymphadenectomy routinely, whereas it is most commonly reserved for
      specific pathological conditions. The presence of lymph node spread is generally
      considered to be the most important prognostic element, and currently,
      radiotherapy of the pelvis appears to be the treatment of choice either as the
      sole postsurgical therapy (57%) or in combination with systemic treatment. An
      adjuvant treatment in stage I lymph node-negative patients is adopted in the
      large majority of the centres (70.5%) when poorly differentiated cancer (46%)
      and/or deep myometrial invasion (33.3%) are present. In this condition,
      radiotherapy appears to be the therapy of choice. Histotype and grading are
      generally recognised as important risk factors and result in treatment
      modification; the high percentage of primary surgical modifications is
      considerable (63.4%) in stage I grade 3 cancers that primarily require
      lymphadenectomy or recourse to radical hysterectomy. The results of our study
      indicate that there is no leading therapy in the advanced stages of endometrial
      cancers, but each therapeutic modality is adopted to more or less the same
      extent.

PMID- 8562155
TI  - Analysis of P-glycoprotein expression in osteosarcoma.
AB  - Current treatment of high-grade osteosarcoma combines surgical removal of the
      lesion with chemotherapy. In this study we evaluated whether the expression of P
      glycoprotein, a protein closely associated with multidrug resistance, may be
      helpful in identifying the patients whose tumours will be further resistant to
      specific agents. By using multidrug-resistant osteosarcoma cell lines as
      standards, the expression of P-glycoprotein was evaluated in 105 cases of primary
      and metastatic osteosarcoma by semiquantitative immunofluorescence.
      Overexpression of the protein was shown in 23% of primary and in 50% of
      metastatic lesions. In 38 cases, homogeneously treated and followed-up for at
      least 24 months, overexpression of P-glycoprotein appeared to be associated with
      a higher relapse rate and with a trend toward a worse outcome. These data support
      the role of P-glycoprotein in the response to chemotherapy and its involvement in
      the determination of the outcome of osteosarcoma patients.

PMID- 8562156
TI  - Primary central nervous system lymphoma: treatment with chemotherapy and
      radiotherapy.
AB  - Between 1989 and 1993, 22 HIV negative patients with primary central nervous
      system lymphoma (PCNLS) were treated with three different regimens. In group A,
      13 patients received preradiotherapy systemic and intrathecal methotrexate (MTX),
      radiotherapy (RT) and three courses of post-RT chemotherapy (CT) with thiotepa
      and procarbazine. In group B, 4 patients received a similar CT only after RT and
      without intrathecal MTX in 3/4 cases. In group C, 5 elderly patients received CT
      alone. In group A, 9/13 patients achieved response after pre-RT CT and 12/13 were
      in complete response (CR) after RT. After a median follow-up of 27 months, 8/13
      (62%) patients are alive but 4 have leucoencephalopathy and cognitive
      dysfunction. In group B, all 4 patients were in CR after RT but the 3 patients
      who did not receive intrathecal MTX died within 10 months with meningeal
      recurrence. In group C, 4/5 patients had a response to CT. 2 patients died of
      recurrent tumour at 5 and 10 months, and 2 are living in CR 11+ and 21+ months
      after diagnosis, 1 after salvage CT. Combined treatment with RT and CT is useful
      in PCNSL but adequate treatment of the meninges is required. CT alone is
      sometimes of value in elderly patients in whom RT is not indicated.

PMID- 8562157
TI  - Combined therapy for primary central nervous system lymphoma in immunocompetent
      patients.
AB  - A retrospective series of 13 immunocompetent patients with histological diagnosis
      of primary central nervous system lymphoma (PCNSL) is presented. The series was
      divided into Group A, 6 patients treated with radiotherapy alone, and Group B, 7
      patients treated with chemotherapy and radiotherapy. Clinicopathological patterns
      were similar for the two groups. In Group A, 4 patients achieved complete
      remission after radiotherapy (45-59.4 Gy) but relapsed within 9 months and died
      within 21 months of diagnosis. 4 Group B patients received chemotherapy followed
      by radiotherapy, and three who received a methotrexate-containing regimen are
      alive and disease-free at 34, 42 and 45 months, while the fourth died after 11
      months. The other 3 subjects in this group were treated with radiotherapy
      followed by chemotherapy, and died within 15 months of diagnosis. Although
      radiotherapy is the standard treatment, chemotherapy has potentially an important
      role in the management of PCNSL. The sequence of combined treatment could be
      crucial to improvement of outcome.

PMID- 8562158
TI  - An approach to the design and implementation of clinical trials of empirical
      antibiotic therapy in febrile and neutropenic cancer patients.
AB  - The results of many clinical trials on empirical therapy in febrile, neutropenic
      cancer patients cannot be readily transferred to the clinical practice, because
      the methodology is often flawed and definitions, study endpoints and eligibility
      criteria differ from trial to trial. This article critically reviews some issues
      related to the design and implementation of randomised clinical trials of
      empirical antibiotic therapy in cancer patients. Within the definition of phase
      III clinical trials, two approaches co-exist, based on the trial's specific aims:
      the "explanatory" approach and the "pragmatic" approach. The usual "explicit" aim
      of clinical trials of empirical therapy in febrile, neutropenic patients has been
      that of comparing the "efficacy" of two regimens. However, this term has been
      more often used with reference to the antibacterial activity of the regimen under
      study (explanatory aim) than to indicate the practical benefits it draws to the
      overall patient population treated for fever and neutropenia (pragmatic aim).
      These two meanings are often taken as perfectly interchangeable, while,
      conversely, they are completely distinct (though not independent) treatment
      effects. Most trials conducted in this patient population in recent years are
      explanatory trials, though not explicitly so, but their results have been widely
      applied to clinical practice, as they were pragmatic trials. In an explanatory
      trial the appropriate endpoint is success or failure (defined by clinical and
      laboratory data) among those patients affected with the specific infection for
      which the study drug is being given, while in pragmatic trials survival is
      probably the more appropriate outcome variable, since they are designed to assess
      the practical benefits that the overall population of febrile and neutropenic
      patients can obtain from the new empirical treatment. Unfortunately, survival is
      not a practical study endpoint for the difficulty in assessing the cause of death
      in this patient population and, especially, for the need for very large sample
      sizes, which might render the implementation problematic even for large,
      multicentre groups. Both types of trials need an intention to treat analysis, but
      this is especially crucial for pragmatic trials, which should not differentiate
      those cases in which success was obtained through multiple treatment
      modifications from those who did not require any treatment change. Obviously,
      this implies that no conclusion should be drawn about the antibacterial activity
      of the study drugs and that the number of treatment modifications should be taken
      into account in the interpretation of the results, especially for quality of life
      and cost evaluations. Information related to fever and signs of infection, age,
      underlying disease, neutropenia and concomitant administration of other
      antibiotics are crucial entry criteria that need to be clearly discussed and
      defined. Finally, the evaluation of toxicity is problematic in this patient
      population, due to the existence of a number of toxigenic factors, including the
      underlying disease, the type of infectious complication, the administration of
      chemotherapy and radiotherapy and the use of parental nutrition. All these
      effects tend to overlap, thus impairing the investigator's ability to detect
      specific drug-related side-effects.

PMID- 8562159
TI  - Restorative effect of total parenteral nutrition on natural killer cell activity
      in malnourished cancer patients.
AB  - Decreased natural killer cell activity (NKCA) is associated with malnutrition in
      both cancer and non-cancer patients. We have studied the effect of total
      parenteral nutrition (TPN) on NKCA in 9 malnourished cancer patients, candidates
      for surgery. TPN was administered for a median of 10 days (range 7-11), providing
      1.5-fold the estimated resting energy expenditure, with 30% as fat.
      Calorie:nitrogen ratio was 150:1. Basal human recombinant interferon-alpha 2a
      (rIFN-alpha 2a) and human recombinant IL-2 rIL-2) activated NKCA were measured,
      as were the main nutritional parameters, prior to and after TPN. NKCA increased
      in all patients and reached the normal range in 5, 3 and 4 subjects,
      respectively, for basal, rIFN-alpha 2a and rIL-2 activated NKCA. As regards
      nutritional assessment, body weight and IgM levels significantly increased from
      47.7 to 50.1 kg and from 174 to 237 mg/dl, respectively. This study demonstrates
      that a 10-day TPN course increases and sometimes restores normal NKCA. Such
      effect was constant and preceded nutritional changes.

PMID- 8562160
TI  - Childhood cancer in Britain: the National Registry of Childhood Tumours and
      incidence rates 1978-1987.
AB  - The National Registry of Childhood Tumours contains population-based data on
      childhood cancers diagnosed throughout Great Britain from 1962 onwards. This
      paper describes the methodology of the Registry, presents incidence rates for
      1978-1987 and describes other uses of the data. Total age-standardised annual
      incidence was 118.3 per million. The most frequent diagnostic groups were
      leukaemias (age-standardised rate 39.8), brain and spinal tumours (27.0),
      lymphomas (11.1), sympathetic nervous system tumours (8.3), kidney tumours (7.7)
      and soft-tissue sarcomas (7.5). Incidence rates were similar to those reported
      from other Western industrialised countries. The data are also used for a wide
      range of epidemiological and other studies. These include analyses of
      geographical variations in incidence, trends in survival, health of long-term
      survivors and their offspring and the genetics of childhood cancer. Information
      is frequently provided for clinicians and research workers, and series of
      specific types of cancer are compiled for further study. The Registry depends for
      the completeness and accuracy of its data on a wide range of organisations and
      individuals, and it is essential that this cooperation continues if the Registry
      is to be maintained.

PMID- 8562161
TI  - Magnetic fields and childhood cancer--a pooled analysis of two Scandinavian
      studies.
AB  - To test the hypothesis that exposure to magnetic fields, of the type generated by
      high voltage installations, increases cancer incidence in children, the original
      data from two case-control studies were pooled. The Swedish study was based on
      children living within 300 m from transmission lines, and the Danish study on the
      total population of Denmark. In both these studies, national cancer registries
      were used to identify cases of leukaemia, lymphoma or central nervous system
      tumour. Controls were selected randomly from the study populations. Magnetic
      field exposure was assessed through theoretical calculations of the magnetic
      fields before the time of diagnosis. An elevated relative risk of childhood
      leukaemia was found for calculated magnetic field levels of > or = 0.2 microT,
      estimated at 2.0 (95% CI 1.0-4.1), and for magnetic field levels of > or = 0.5
      microT, estimated at 5.1 (95% CI 2.1-12.6). The results support the hypothesis of
      an association between magnetic fields and childhood leukaemia.

PMID- 8562162
TI  - In search of the best upper age limit for breast cancer screening.
AB  - The aim of this study was to determine the best upper age limit for a breast
      cancer screening programme. We used a model-based study using optimistic and
      pessimistic assumptions, concerning improvement of prognosis due to screen
      detection and duration of the period of mammographic detectability, resulting in
      upper and lower limits for favourable and unfavourable effects. Under pessimistic
      assumptions, the balance between positive and negative effects of screening
      remains favourable up to an age of around 80 years. Under optimistic assumptions,
      this balance never becomes clearly negative with increase of the upper age limit
      of a screening programme. When including the costs in the analysis, the balance
      between effects and costs of increasing the upper age limit from 69 to 75 years
      is likely to be at least as favourable as intensifying a screening programme
      within the age group 50-69 years. A further increase leads to a markedly less
      favourable balance. Competing causes of death do not lead to missing net benefit
      for women up to at least age 80 years, but the disproportional rise of negative
      effects of screening with age in older women leads to a lower cost-effectiveness
      ratio than intensifying screening at ages 50-69 years.

PMID- 8562163
TI  - Trends in incidence of testicular cancer in Norway 1955-1992.
AB  - The aim of this study was to explore the incidence of testicular cancer (TC) in
      Norway, and thereby to increase the understanding of aetiological factors. From
      1995 to 1992, a total number of 3927 TC cases were recorded in Norway, of which
      51% were seminomas, 45% non-seminomas and 4% other and unspecified types. The age
      standardised incidence rate increased from 2.7 to 8.5 per 100,000. The age
      specific incidence rate increased in all age groups, but was most marked in the
      younger population. The significance of birth cohort as a risk factor for
      development of TC was confirmed. The incidence by birth cohorts from 1916 to 1970
      showed an increase by later birth cohorts during the whole period, with the
      exception of a marked fall for the cohort born during the Second World War. The
      largest increase occurred after the war. We conclude that environmental factors
      acting very early in life are of significance in the development of TC.

PMID- 8562164
TI  - Multistep progression from an oestrogen-dependent growth towards an autonomous
      growth in breast carcinogenesis.
AB  - We investigated the relationship between hormone receptor status and cellular
      proliferation in a series of proliferative epithelial breast lesions in an
      attempt to clarify the putative role of this interaction in the process of breast
      carcinogenesis. The separation of oestrogen receptor (ER) positive and ER
      negative cases revealed that in hyperplastic breast epithelium (with and without
      atypia) the ER positive cases had a higher proliferation rate than that of ER
      negative cases. Conversely, in ductal carcinomas (both in situ and invasive), ER
      negative cases had rates of proliferation higher than those observed among the ER
      positive cases. The observation of higher proliferation in ER positive benign
      proliferative breast lesions fits with the concept of an initial hormone
      dependent status in breast carcinogenesis. According to this assumption,
      activation of ER by hormone increases the possibility that cells may undergo
      malignant transformation. Although we are limited by our static view of the
      process, our results point to the existence of successive steps of progression
      from a hormone-dependent towards an autonomous growth. The demonstration of
      higher proliferation in ER-negative carcinomas, from the in situ phase onwards,
      reinforces the hypothesis that breast cancer progression is paralleled by a
      progressive hormone independence.

PMID- 8562165
TI  - Glucocorticoid receptors and growth inhibitory effects of dexamethasone in human
      lung cancer cell lines.
AB  - Expression of glucocorticoid receptors (GR) and growth effects of dexamethasone
      and the antiglucocorticoid RU-486 were investigated in six cell lines originating
      from small cell lung cancer (SCLC) and 13 cell lines from non-small cell lung
      cancer (NSCLC; four adenocarcinoma, four squamous cell carcinoma, four large cell
      carcinoma and one mesothelioma). All cell lines contained specific and saturable
      binding sites for the synthetic glucocorticoid dexamethasone, as determined by
      whole cell assays and by cytosolic receptor assays. The presence of GRs in the
      carcinoma cells was confirmed by immunocytochemistry. In NSCLC cell lines, GRs
      were present in large amounts (37-638 fmol/mg cytosolic protein). In SCLC cell
      lines, GRs were also detectable but in considerably lower concentrations. Growth
      inhibitory effects of dexamethasone were seen in the cultures of two squamous
      cell carcinoma lines (EPLC-32M1 and NCI-H157), one adenocarcinoma line (A-549),
      one large cell carcinoma cell line (LCLC-97TM1) and the cell line of a
      mesothelioma (MSTO-211H). All cell lines responsive to dexamethasone had high GR
      concentrations (> or = 164 fmol/mg cytosolic protein). The antiglucocorticoid RU
      486 was virtually inactive when administered alone but was able to block the
      growth-inhibitory effect of dexamethasone. The results indicate that
      glucocorticoids may inhibit the progression of individual non-small cell lung
      carcinoma.

PMID- 8562166
TI  - Cytokine modulation of epidermal growth factor receptor expression on bladder
      cancer cells is not a major contributor to the antitumour activity of cytokines.
AB  - Epidermal growth factor is a potential mitogen for many different human tumours.
      Its effect is mediated via a bispecific receptor (EGFR), the expression of which
      correlates well with invasive disease. We investigated the modulation of EGFR by
      cytokines produced following bacillus Calmette Guerin (BCG)-immunotherapy. Our
      data demonstrate the IFN gamma, TNF alpha and IL-1 alpha can decrease the
      expression of EGFR on some bladder tumour cell lines. IFN gamma reduced EGFR
      expression on two of eight cell lines (RT4, SD). However, IL-1 and TNF did not
      share this activity. When cells were treated with a combination of all three
      cytokines, EGFR was decreased on three cell lines (RT4, RT112, SD) and
      furthermore, the change in the receptor expression was even more marked.
      Treatment with phorbol ester (thereby activating protein kinase C) resulted in
      rapid disappearance of the receptor from the cell surface. Interestingly, the
      decrease of EGFR expression did not require protein synthesis. Although the
      cytokines studied could down modulate EGFR, this only occurred on three out of
      eight cell lines; therefore, it is unlikely that the suppression of proliferative
      activity caused by cytokine-induced decrease of EGFR expression is central to the
      antitumour action of BCG therapy, but in a proportion of tumours this mechanism
      may be involved.

PMID- 8562167
TI  - Cytotoxicity of TGF alpha-PE40 and correlation to expression of epidermal growth
      factor receptor.
AB  - TGF alpha-PE40 is a chimeric protein composed of transforming growth factor alpha
      (TGF alpha) linked to a modified Pseudomonas exotoxin (PE40). We tested the in
      vitro cytotoxicity of TGF alpha-PE40 on 23 different solid human tumour
      xenografts established in nude mice and human bone marrow cells from healthy
      donors, utilising a modified clonogenic assay. In order to distinguish non
      specific toxicity from the targeted effects of TGF alpha-PE40, epidermal growth
      factor receptor (EGFR) expression of the tumours studied was assessed by Northern
      blot, slot blot and immunohistochemistry. TGF alpha-PE40 demonstrated
      differential cytotoxicity on human tumour xenografts in the clonogenic assay. No
      toxicity on human bone marrow cells was observed. In vitro activity of TGF alpha
      PE40 showed a significant correlation with the expression of EGF receptors as
      determined by immunohistochemistry and slot blot. Further studies will be
      performed in order to determine the in vivo activity of this compound in tumour
      bearing nude mice.

PMID- 8562168
TI  - Expression of CD44v6 is associated with cellular dysplasia in colorectal
      epithelial cells.
AB  - There is increasing evidence that the expression of variants of the glycoprotein
      CD44 is related to the invasive and metastatic potential of tumour cells. By in
      situ hybridisation, we analysed the cellular expression of human homologues of a
      rat metastasis-associated CD44 variant v6 in invasive and non-invasive colorectal
      neoplasia and normal colonic mucosa. No specific hybridisation signals could be
      detected in epithelial cells of the normal crypt (n = 10). In contrast, we found
      moderate epithelial hybridisation signals in adenomatous polyps of mild dysplasia
      (n = 6). Adenoma cells of moderate or severe dysplasia (n = 7) showed increased
      hybridisation signals compared to mildly dysplastic adenomas (P < or = 0.01). We
      could not demonstrate significant differences in CD44v6 transcript levels between
      cells of dysplastic adenoma and primary adenocarcinoma (n = 11) (P > or = 0.05).
      Furthermore, we were not able to demonstrate a significant difference between
      primary and metastatic tumours (n = 7) (P > or = 0.05). However, there was a
      significant difference between metastatic carcinoma and adenomas with advanced
      dysplasia (P < or = 0.01). Our data demonstrate that significant transcriptional
      expression of CD44v6 is not confined to invasive tumour cells, but is already
      detectable in cells of adenomatous polyps showing mild dysplasia. The results of
      this study show a close relationship between cellular dysplasia and steady state
      levels of CD44 variant v6 transcripts in colorectal neoplasms.

PMID- 8562169
TI  - Effects of hexadecylphosphocholine on membrane phospholipid metabolism in human
      tumour cells.
AB  - Hexadecylphosphocholine (HePC) is an analogue of the antiproliferative
      alkyllysophospholipids (ALP). As these lipid-like compounds interfere with
      membrane lipid metabolism at several sites, we studied the effects of HePC on
      uptake and metabolism of inositol and choline, two important phospholipid
      precursor molecules in two sensitive cell lines, Raji and KB, and in a resistant
      variant of KB cells, KBr. HePC substantially inhibited the membrane uptake of
      inositol and of choline in KB and Raji. Inositol uptake of KBr cells was
      constitutively low and was not further decreased by HePC. In all three cell
      lines, uptake inhibition of choline was less pronounced. Uptake inhibition showed
      characteristics of a non-specific effect, probably due to the physicochemical
      properties of HePC as a "lyso" structure. Decreased uptake of inositol did not
      affect phosphoinositide synthesis. Cellular phosphatidylcholine (PC) metabolism
      seemed to be affected through inhibition of choline incorporation and enhancement
      of PC degradation in the two sensitive cells. In KBr cells, these effects were
      not observed.

PMID- 8562170
TI  - Gastrin sensitivity of primary human colorectal cancer: the effect of gastrin
      receptor antagonism.
AB  - The purpose of this study was to determine the effect of the gastrin receptor
      antagonist, CR2093, on basal and gastrin-stimulated growth of primary human
      colorectal adenocarcinomas and to relate this to gastrin receptor expression.
      Tumour cells, derived from surgical specimens by enzymatic disaggregation, were
      grown on matrices of type I collagen and irradiated fibroblasts. Gastrin receptor
      expression was measured by using a mouse monoclonal antibody directed against the
      gastrin receptor and an avidin-biotin immunocytochemical method. Increased growth
      in the presence of gastrin-17 (used at physiological concentrations and as
      assessed by [3H] thymidine uptake) was shown in 16/34 (47%) tumours. CR2093
      significantly reversed this stimulated growth (P < 0.05, one way analysis of
      variance) in 9/16 (56.3%) of the tumours and inhibited the basal growth of 11/34
      (32.4%). Basal growth inhibition was reversed by gastrin-17 in 82% (9/11) of
      tumours. Gastrin receptor expression was widespread, but was not related to the
      degree of growth response to gastrin, and there was no significant correlation
      between intensity of receptor expression and inhibition of basal growth by
      CR2093. In conclusion, both gastrin-stimulated and basal growth of primary human
      colorectal can be inhibited by gastrin receptor antagonism, but gastrin receptor
      expression does not predict the sensitivity of tumours to (i) the proliferative
      effects of gastrin or (ii) the inhibitory effects of a gastrin receptor
      antagonist on basal growth. Antigastrin agents may have clinical value in the
      treatment of gastrin-sensitive colorectal tumours, and gastrin receptor
      expression may be related to endogenous gastrin production by colorectal tumour
      cells.

PMID- 8562171
TI  - Intralesional sustained-release chemotherapy with therapeutic implants for
      treatment of canine sun-induced squamous cell carcinoma.
AB  - Squamous cell carcinoma (SCC) is the most frequently reported malignant
      epithelial tumour in dogs. Canine sun-induced SCC represents a useful animal
      model to evaluate new therapeutic modalities for possible human applications. We
      evaluated the safety and efficacy of treating sun-induced SCC in dogs with
      intralesional sustained-released chemotherapeutic gel implants that contained
      collagen, epinephrine (epi), and either 5-fluorouracil (5-FU) or cisplatin
      (CDDP). Dogs with large, single SCC or fields of multiple SCC were treated with 5
      FU/epi gel for a minimum of three weekly injections. Dogs without a complete
      response were then treated with CDDP/epi gel for a minimum of three weekly
      treatments. We treated from one to 11 primary, recurrent, or refractory SCC per
      dog (tumour size 0.2-92.4 cm2; mean cumulative tumour area of 40.7 cm2 per dog).
      All dogs had at least 50% reduction in cumulative tumour area after treatment
      with 5-FU/epi gel. More than half (seven of 13) had complete resolution of SCC
      after treatment with 5-FU/epi gel or CDDP/epi gel. Minimal local tissue reactions
      were noted; no systemic toxicity occurred. Sustained-release chemotherapy using
      intralesional 5-FU/epi gel and CDDP/epi gel therapeutic implants is effective in
      treating canine sun-induced SCC of the skin.

PMID- 8562172
TI  - The amino-terminal phosphorylation sites of C-MYC are frequently mutated in
      Burkitt's lymphoma lines but not in mouse plasmacytomas and rat immunocytomas.
AB  - We sequenced the region encoding the amino-terminal phosphorylation sites of C
      MYC in the Ig/MYC translocation-carrying Burkitt lymphomas (BL), mouse
      plasmacytomas (MPC) and rat immunocytomas (RIC). Mutations affecting the Thr-58
      codon or the immediate flanking region were found in seven of the 10 in vitro
      propagated BL lines. No mutations were found in any of the eight BL biopsies
      analysed. Germ-line sequences were also found in six in vivo and five in vitro
      passaged MPCs and in four in vivo transplanted RICs. These findings indicate that
      mutations in this region do not represent a general phenomena in Ig/MYC
      translocation-carrying tumours, but may confer growth advantage on BL cells under
      continuous in vitro propagation.

PMID- 8562173
TI  - Treatment of advanced colorectal cancer with high-dose intensity folinic acid and
      5-fluorouracil plus supportive care.
AB  - This randomised clinical trial, involving patients with advanced colorectal
      cancer, was carried out to compare the effectiveness of accelerated folinic acid
      (FA) plus 5-fluorouracil (5-FU) with that of the conventional regimen of 5-FU
      alone. Both regimens were administered with simulataneous supportive care. 185
      patients were eligible: 94 were randomly allocated to receive FA 200 mg/m2 i.v.
      plus 5-FU 400 mg/m2 i.v. on days 1-5 every 3 weeks; and 91 to receive 5-FU 400
      mg/m2 i.v. on days 1-5 every 4 weeks. The response rate was 33.3% in the
      accelerated FA/5-FU and 18.6% in the 5-FU arm (P = 0.045). Median survival was
      13.5 months in the FA/5-FU arm and 7.5 months in the 5-FU arm (P = 0.039).
      Toxicity was mild and slightly more pronounced in the FA/5-FU arm (P = 0.078).
      This study indicates that, in patients with advanced colorectal cancer,
      accelerated chemotherapy with FA and 5-FU and simultaneous supportive care is
      capable of achieving a higher response rate and longer survival than conventional
      5-FU alone, without severe toxicity.

PMID- 8562174
TI  - Colonic adenocarcinoma associated ectopic ACTH secretion: a case history.
AB  - A 57-year-old woman developed features of Cushing's syndrome after resection of a
      Duke's C adenocarcinoma of the sigmoid colon. Biochemical and endocrine
      investigation indicated ectopic production of adrenocorticotrophic hormone (ACTH)
      as the cause for her condition. Hepatic metastases were detected by computed
      tomography (CT) scan. Histology of the original tumour displayed neuroendocrine
      characteristics but no definite evidence of ACTH synthesis. Treatment was
      instituted to control her hypercortisolism, and chemotherapy initiated to reduce
      the production of ectopic hormone. A clinical, biochemical and radiological
      response was obtained with complete resolution of her Cushing's syndrome. The
      tumour relapsed after several months with distant metastases, but no further
      endocrine abnormality was noted. A review of ectopic ACTH producing
      adenocarcinoma is given along with a discussion of the major pathological and
      therapeutic features of the case.

PMID- 8562175
TI  - Mixed response to chemotherapy, a new entity in soft tissue sarcomas.

PMID- 8562176
TI  - Mitoxantrone, 5-fluorouracil and leucovorin in metastatic breast cancer.

PMID- 8562177
TI  - Recombinant granulocyte colony stimulating factor in the treatment of small cell
      lung cancer: a long-term follow-up.

PMID- 8562178
TI  - Increasing incidence of cancer of the sigmoid and ascending colon for men in
      south-east Netherlands.

PMID- 8562179
TI  - The use of the tumour marker CA19-9 in evaluating the response to tamoxifen
      therapy in patients with unresectable adenocarcinoma of the pancreas.

PMID- 8562180
TI  - Detection of BCL-2 RNA in low grade tumours of the urinary bladder.

PMID- 8562181
TI  - Malignant teratoma undifferentiated (MTU) metastasising solely as differentiated
      teratoma: implications for the aetiology of residual differentiated disease
      following successful chemotherapy.

PMID- 8562182
TI  - Pregnancy during alpha-interferon therapy in patients with advanced Hodgkin's
      disease.

PMID- 8562183
TI  - Cytotoxic agents with activity in breast cancer patients previously exposed to
      anthracyclines: current status and future prospects.

PMID- 8562184
TI  - Anthracycline resistance in breast cancer: clinical applications of current
      knowledge.
AB  - Anthracyclines are highly effective antineoplastic agents for the treatment of
      breast cancer. Nevertheless, essentially all breast cancer patients have tumours
      which are intrinsically resistant or which develop resistance during the course
      of therapy. Clinical trials provide indirect information on the nature of
      anthracycline resistance and work in the basic sciences has demonstrated
      molecular mechanisms which play a role. Initial clinical attempts to exploit and
      translate these mechanisms to predict, and interfere with, anthracycline
      resistance have met with mixed success, and have not yet led to accepted clinical
      applications.

PMID- 8562185
TI  - Multidrug resistance in breast cancer: mechanisms, strategies.

PMID- 8562186
TI  - Pharmacokinetics, targeting and delivery systems in anthracycline-resistant
      cancers.

PMID- 8562187
TI  - High dose chemotherapy with haemopoietic support for breast cancer.

PMID- 8562188
TI  - [Prognostic significance of delayed cutaneous reactivity in 5-year survival in
      colorectal cancer: a prospective study].
AB  - A series of 84 patients operated on for colorrectal cancer-Duke's stages A:6,
      B:22, C:51 and D:5- are studied prospectively and with a 5 year follow-up. All of
      them were treated in the same hospital and with identical criteria during a
      period of time of two years. Immunoglobulins (A, G, M) and skin reactivity
      measured through a multiantigen device were determined preoperatively and at 48
      hours and 30 days after operation. Data analysis was done once real survival at 5
      years was known. Immunoglobulins changes showed no significance in relation to
      survival in this series. Preoperative skin reactivity values measured in mms
      demonstrated prognostic significance for patients in stage C when considering
      survivors -p < 0.05- and decreased -p < 0.01- at five years. Numerical values of
      skin reactivity done with a delayed hypersensitivity multiantigen compound may
      represent and additional prognostic factor to be considered in advanced
      colorrectal cancer patients.

PMID- 8562189
TI  - [Left hemicolectomy and intraoperative antegrade lavage in emergency surgery of
      the left colon].
AB  - We report our results with a left colonic resection and intraoperative antegrade
      colonic irrigation technique with primary anastomosis. Thirty five consecutive
      patients operated on in the Emergency Surgical Ward are presented. Twenty five
      with large bowel occlusion and 10 with sigma perforation. Anastomotic leakage (2
      patients, 5.7%) and postoperative hospital stay (mean 15 days) were similar to
      cases of elective surgery. The intraoperative antegrade colonic irrigation
      technique has become the first choice in our Department to treat any patient with
      left colonic occlusion or perforation. Only patients with faecal peritonitis or
      ischemic colon were excluded.

PMID- 8562190
TI  - [Influence of liver cirrhosis with and without ascites on ventilatory mechanics].
AB  - BACKGROUND: The thoracic cavity plays an important role in the mechanical
      ventilatory function, and the alteration of some of its structures, such as those
      which occur in decompensated cirrhosis of the liver, for example the presence of
      ascites and muscle atrophy, directly influence its normal function. METHODS: In
      the present study we have evaluated the ventilatory function and respiratory
      muscular tension by means of the calculation of volumes, flows and resistances of
      the airways, and also the maximum inspiratory and expiratory pressures (Pimax,
      Pemax). PATIENTS: One hundred patients with liver cirrhosis and ascites without
      associated respiratory illness, mean age 57 +/- 15 years (range 32-80), were
      studied. We evaluated the respiratory function before and after the disappearance
      of the ascites. RESULTS: A restrictive pattern was evident, and various
      parameters were altered. The most affected being that of the reserve expiratory
      volume. No associated bronchial obstruction was observed. Respiratory muscular
      tension was decreased in both the Pimax and the Pemax. With the disappearance of
      the ascites we found an improvement in the affected parameters, but this did not
      reach normality. CONCLUSION: In liver cirrhosis associated with ascites, the most
      common respiratory pattern, is a decrease in ventilatory function of a
      restrictive type, and also a decrease in the respiratory muscular tension. These
      alterations improve after the resolution of the ascites.

PMID- 8562191
TI  - [Predictive analysis of the response to treatment with diuretics of patients with
      liver cirrhosis and ascites].
AB  - Our aim was to develop and validate a prognostic model to predict the evolution
      of cirrhotic patients admitted to the hospital because of ascites and treated
      with diuretics. Two hundred and two patients were evaluated. After collection of
      clinical and laboratory data, a prognosis of the response to diuretics was given
      by one of us. After univariate analysis, 37 parameters were used to construct a
      database. A new prognosis was obtained for each patient comparing his/her data
      with the database, with the help of a computer and using Bayes' theorem. Gender:
      female, poor general status, disturbed consciousness, increased serum glucose,
      increased BUN, low prothrombin time, increased bilirubin, leucocytosis,
      thrombopenia and low urine sodium were associated with a poor response to
      diuretics. Sensitivity and specificity of clinical and computer prognosis were
      similar. Computer prognosis allowed the classification of patients in groups of
      risk which showed a different evolution and improved the accuracy of the clinical
      prognosis. We conclude that the objective analysis of clinical and laboratory
      data is useful to improve the accuracy of the prediction of the evolution in
      cirrhotic patients with ascites treated with diuretics.

PMID- 8562192
TI  - [Plasma levels of alanine aminotransferase in experimental liver necrosis induced
      by overdosage of paracetamol in mice].
AB  - OBJECTIVE: To investigate the correlation between the hepatocellular damage and
      ALT plasma level after paracetamol overdosage in mice. EXPERIMENTAL DESIGN: A
      total of 30 female, 16 week-old mice (Souris OF1 strain), weighing 25-30 g were
      used. After 18 hours fast period, single doses of 500 mg/kg of paracetamol were
      administered intraperitoneally. The animals were killed by decapitation 24 hours
      after paracetamol injection, fasting being continued, although free access to
      water was allowed. ALT plasma levels were determined. The hepatocellular damage
      was graded from 0-4 (+). Plasma levels of mercapturate conjugate were measured by
      HPLC. RESULTS: The study showed a statistically significant correlation (r = 0.8,
      p = 0.00001) between ALT plasma levels and the degree of hepatocellular damage
      but not with concentrations of mercapturate conjugate. CONCLUSIONS: These
      findings suggest that ALT plasma levels give a reliable indication of the
      severity of hepatic necrosis, after experimental paracetamol overdosage in mice.

PMID- 8562193
TI  - [Acute pancreatitis. A prospective epidemiological study in the province of
      Alicante. A Hospital Group for Study of Digestive Diseases in Alicante].
AB  - OBJECTIVE: To gather epidemiological data on acute pancreatitis (AP) in Alicante
      area. EXPERIMENTAL DESIGN: A prospective study of patients admitted to all public
      hospitals with AP during 1991. PATIENTS: Patients over 14 years, with elevation
      of serum amylase and a consistent clinical presentation, or in whom AP was
      confirmed at laparotomy or postmortem. RESULTS: We identified 473 episodes of AP
      in 450 patients (236 males and 214 females). The mean age was 59.4 years. The
      annual incidence was 451 per million habitants/year. The commonest aetiology was
      biliary (52%) followed by idiopathic forms (24.7%), alcoholic (20.2%) and
      miscellaneous (2.9%). The overall mortality rate was 5.1%. Male were more
      frequently affected below 50 years of age (2.4 men/1 woman); the ratio being
      balanced above this age. Biliary etiology was more frequent in women, (63.5%),
      while alcoholic forms were more frequent in man (96.8%). 5.1% of patients
      presented more than one episode of AP during the year analysed. AP involved the
      0.58% of the all patients admitted to the hospitals and the 0.14% of the all
      patients attended in hospital emergencies.

PMID- 8562194
TI  - [Regulation of gastric acid secretion].

PMID- 8562195
TI  - [Jejuno-ileal volvulus, a rare cause of intestinal obstruction].
AB  - Volvulus of the small bowel without predisposing anatomical defects is a rare
      cause of acute intestinal obstruction in the Western world, and its incidence is
      decreasing in Europe and America, although it is common in others parts of the
      world. The causes of primary volvulus of the small bowel and the mechanism of
      rotation of the entire root of the mesentery remain unexplained. Several
      anatomical and dietary factors have been implicated. This theory requires strong
      peristalsis, tense, firm abdominal muscles and feeding pattern of very bulky
      meals taken at long intervals. In the present case, a large quantity of bulky
      poorly digested food consumed previously, and strong abdominal muscles are in
      keeping with the above theory.

PMID- 8562196
TI  - [Idiopathic granulomatous appendicitis or Crohn's disease confined to the
      appendix?].
AB  - Crohn's disease limited to the appendix is uncommon. When Crohn's disease affects
      the appendix it typically has a longer clinical course than most cases of acute
      appendicitis. The diagnosis is histological. Appendiceal Crohn's disease has a
      benign course after surgery, and that's why some authors believe that it could be
      a different entity which should be better addressed to as "Idiopathic
      Granulomatosus Appendicitis". We present three new cases of Crohn's disease
      limited to the appendix.

PMID- 8562197
TI  - [Spontaneous bacterial peritonitis caused by Listeria monocytogenes].
AB  - Listeria monocytogenes is a gram-positive coccobacillus that produces infections
      in both the normal and the compromised host. Symptomatic bacteremia and pulmonary
      infection or meningitis are the most common clinical presentations in adults.
      According to a current review of the literature, Listeria is a rare bacteria that
      may produce spontaneous bacterial peritonitis (23 cases reported). Listeria
      peritonitis occurs in more than two-thirds of the cases in patients with chronic
      liver disease, but may also occur in patients with malignancy or undergoing
      peritoneal dialysis. We describe two cases of SBP in cirrhotic patients, one with
      alcoholic cirrhosis and other due to HCV infection. One patient also presented
      with acute meningitis. Peritonitis due to Listeria was clinically and
      analytically similar to any SBP. Third-generation cephalosporins commonly used in
      the therapy of SBP, are ineffective in this infection. Ampicillin is the drug of
      choice, although it should be used in combination therapy usually with an
      aminoglycoside. The mortality from Listeria peritonitis is similar to that of
      other SBP (17%).

PMID- 8562198
TI  - [Laparoscopic diagnosis of hepatic angiomas after erroneous imaging techniques].
AB  - Hemangiomas are de most frequent benign liver tumours. Their clinical relevance
      is small but they can cause to the patient and/or the physician a great worry
      because can be indistinguishable from hepatic malignances. From 1991 to 1994 five
      patients with liver hemangiomas were diagnosed by laparoscopy after a erroneous
      and/or contradictory interpretation by various imaging techniques. In four cases
      hemangiomas resembled metastatic carcinoma of the liver, and in the other patient
      hemangioma was interpreted as focal nodular hyperplasia. Diagnosis and treatment
      are discussed.

PMID- 8562199
TI  - [Eosinophilic cholecystitis associated with rupture of hepatic hydatid cyst of
      the bile ducts].
AB  - Eosinophilic cholecystitis is a rare finding characterized by an inflammatory
      infiltrate composed primarily of eosinophils. We report a case of eosinophilic
      cholecystitis associated with hepatic hydatic cyst ruptured into the biliary
      tract. The release of hydatid cyst content into the biliary tract may have
      induced a hypersensitivity reaction with numerous eosinophils in the gallbladder
      wall.

PMID- 8562200
TI  - [Transpapillary endoscopic drainage of pancreatic pseudocyst].
AB  - Drainage of pancreatic pseudocysts can be achieved by means of endoscopy. In this
      paper we report a case of a pancreatic pseudocyst of ten centimeters in diameter,
      that was successfully managed by insertion of a nasocystic drainage through the
      papilla of Vater. The procedure was simple and complications were absent.
      Transpapillary drainage of pancreatic pseudocysts is an effective procedure.

PMID- 8562201
TI  - [Rendu-Osler disease with liver involvement. A color Doppler study].

PMID- 8562202
TI  - [Ampulloma in a patient with type I neurofibromatosis].

PMID- 8562203
TI  - [Zinc in acute pancreatitis in man].

PMID- 8562204
TI  - [Eradication of Helicobacter pylori and hemorrhagic recurrence of duodenal
      ulcer].

PMID- 8562205
TI  - [Psoriasis with liver disease].

PMID- 8562206
TI  - Cancer research in Hispanic populations in the United States.

PMID- 8562207
TI  - The emerging Hispanic population: a foundation for cancer prevention and control.
AB  - Although making up only 9% of the U.S. population and concentrated in urban areas
      of a few states, Hispanics are found throughout the country and represent a mix
      of historical and cultural backgrounds. This diverse group cuts across racial and
      ethnic lines, with origins in various countries of Europe and North, Central, and
      South America. The Hispanic population has several distinguishing demographic
      characteristics, including its rapid growth rate, relative youth, and low
      educational and socioeconomic levels. However, considerable differences exist
      among Hispanic groups, particularly in median age, household size, education, and
      family income. The majority of Hispanics face barriers to health care access,
      including a lack of health insurance coverage, underrepresentation in health care
      fields, and cultural and language differences. These distinct demographic
      characteristics and barriers have a direct impact on the risk of cancer in
      Hispanics and on the development of prevention and control strategies. The
      purpose of this review is to examine the demographic and socioeconomic
      characteristics of Hispanics and issues of access to health care among this
      population within the context of cancer prevention and control.

PMID- 8562208
TI  - Social theory, social action, and intervention research: implications for cancer
      prevention among Latinos.

PMID- 8562209
TI  - From ethnography to intervention: developing a breast cancer control program for
      Latinas.
AB  - Latinas are less likely than Anglo women to have appropriate breast cancer
      screening for reasons that may include culturally based beliefs as well as
      socioeconomic factors. This study employed ethnographic methods to explore breast
      cancer-related knowledge, attitudes, and behaviors among Latinas, Anglo women,
      and physicians, tested the generalizability of the findings in a telephone survey
      of randomly selected women, and used the results to design a culturally sensitive
      breast cancer control intervention in Orange County, Calif. Respondents for the
      ethnographic interviews included 28 Salvadoran immigrants, 39 Mexican immigrants,
      27 Chicanas (U.S.-born Latinas of Mexican heritage), 27 Anglo women, and 30
      physicians selected through organization-based network sampling. Latinas had very
      different beliefs about risk factors for breast cancer and held more fatalistic
      attitudes about the disease. For example, they believed that trauma to the breast
      was among the most important risk factors. Results of a telephone survey of 1225
      randomly selected women (269 U.S.-born Latinas, 425 Mexican immigrants, 109 other
      Latina immigrants, and 422 Anglo women) generally confirmed the dissimilar
      beliefs among Latinas and Anglo women. The findings influenced our decision to
      design and pilot-test a breast cancer control intervention based on Bandura's
      self-efficacy theory and Freire's empowerment pedagogy. The methodology and
      findings of this study have important implications for future cancer control
      research and interventions.

PMID- 8562210
TI  - Use of Spanish surnames to identify Latinos: comparison to self-identification.
AB  - Difficulties in identification of Latinos from secondary datasets have often been
      addressed by the use of a Spanish surname list. To evaluate the sensitivity and
      specificity of the 1980 U.S. Census Spanish surname list in correctly identifying
      Latino ethnicity, we conducted a cross-sectional survey of adult members of a
      prepaid health plan in the San Francisco Bay Area. We compared a randomly
      selected list of 1345 Spanish surnames and 717 non-Spanish surnames from health
      plan membership lists with their self-identified race and ethnicity obtained by
      telephone interviews. The sample was stratified according to surname group
      (Spanish or non-Spanish), sex, age, and county. Compared with self-identified
      ethnicity, a Spanish surname was 88.4% sensitive in identifying Latino men and
      70.4% sensitive in identifying Latina women. The non-Spanish surname list was
      94.1% sensitive and 95.0% specific in correctly identifying non-Latinos. Although
      the overall negative predictive value was 97.8%, the positive predictive value of
      a Spanish surname was only 68.3% for men and 55.7% for women. The low positive
      predictive value was largely due to the 316 (61%) Filipinos among the 517 persons
      with Spanish surnames who were not Latinos. We conclude that the use of the
      Spanish surname list alone to ascertain race and ethnicity in the San Francisco
      Bay Area both falsely identifies a large number of non-Latino persons as Latino
      and fails to identify a small proportion of Latinos. Although the level of
      sensitivity and specificity for Spanish surnames will vary with the area under
      study, this source of inaccuracy must be considered in studies that plan to use
      data based on Spanish surnames.

PMID- 8562211
TI  - Community level cancer control in a Texas barrio: Part I--Theoretical basis,
      implementation, and process evaluation.
AB  - A theory-based program that used peer modeling and a network of peer
      communicators to promote breast and cervical cancer screening was designed and
      implemented in a barrio of San Antonio with a population of approximately 25,000
      adult women. The implementation process was evaluated and documented through
      field notes, archival documents, content analyses, interviews, surveys, etc. Over
      a 21-month period, a total of 156 new stories and a network for distribution of
      more than 80,000 print pieces carried messages about positive role models who
      were receiving Pap smears and mammograms. A group of 85 volunteers were recruited
      to promote screening; these volunteers reached 2000-3000 women each month with
      personal contacts in which cancer screening was encouraged. A small group of
      volunteers offered particularly intensive assistance to their peers, e.g.,
      helping them to make and keep appointments for screening examinations. The
      theoretical communication model for the program, which maximizes audience and
      community participation as sources and channels for messages, was well suited for
      the cross-cultural application presented here.

PMID- 8562212
TI  - Community level cancer control in a Texas barrio: Part II--Base-line and
      preliminary outcome findings.
AB  - In a quasiexperimental demonstration study, screening rates for breast and
      cervical cancers were measured among Mexican-American women in selected areas of
      San Antonio and Houston, Tex. This research was primarily designed to evaluate a
      cancer-screening promotion program in San Antonio by comparing changes in
      screening rates in panels from the two barrio communities. In a base-line
      population survey, we found a small, but significant, proportion of women (10%
      15%) lacking Pap smears and a larger proportion (30%-40%) lacking mammography. In
      a panel study following women who lacked screening at base line, there was a
      trend toward greater Pap smear use among younger women and a significant increase
      in mammography for all age groups in San Antonio compared with groups in Houston.
      Although there was a difference in language use between the communities, rates of
      newly initiated screening within the communities were similar among monolingual
      Spanish speakers and among those who used English, supporting the hypothesis that
      the program increased both groups' participation in breast-cancer screening.

PMID- 8562213
TI  - Mobilizing churches for health promotion in Latino communities: Companeros en la
      Salud.
AB  - Companeros en la Salud (Partners in Health) is a 3-year project funded by the
      National Cancer Institute to conduct a church-based health promotion program
      whose aim is to reduce the risk of breast, cervical, and diet-related cancers in
      Latino/Hispanic women by increasing their knowledge of preventive behaviors,
      motivating healthy behavior change, and increasing their access to and
      utilization of preventive health services. From a systems perspective, churches
      serve as miniature, dynamic communities that present an opportunity for
      developing and implementing a program of health promotion. An analysis of church,
      Promotora (peer health worker), and participant characteristics from the
      preintervention base-line data revealed a naturally occurring segmentation of
      churches by congregation size and denomination. The Catholic churches almost
      exclusively were larger, whereas the Protestant churches almost exclusively were
      smaller. An analysis of the psychosocial characteristics of the various Latino
      women, when stratified by church congregation size, revealed that the women from
      the smaller, Protestant churches were poorer, had a lower level of acculturation,
      and had lower lifetime rates of clinical breast examinations. These results
      suggested greater resource deficits and a relatively higher need for Promotora
      outreach services for women from the smaller, Protestant churches. Implications
      are presented for differential approaches to effective health promotion among
      various types of churches.

PMID- 8562215
TI  - Use of cancer-screening tests in the San Francisco Bay area: comparison of
      Latinos and Anglos.
AB  - BACKGROUND: Compared with Anglos (non-Latino whites), incidences of breast and
      colorectal cancers are lower for Latinos and incidences of cervical cancer are
      higher for Latinos. In regional and national studies, Latinos obtain fewer cancer
      screening tests for cervical, breast, and colorectal cancers when compared with
      Anglo populations. It remains unclear if these differences are due solely to
      socioeconomic status. PURPOSE: To evaluate self-reported use of these tests by
      ethnicity, we conducted telephone interviews about the use of the Pap smear,
      clinical breast examination, mammogram, rectal examination, fecal occult blood
      test, and sigmoidoscopy. METHODS: Cross-sectional, random-digit dialing telephone
      surveys of Latino and Anglo adults, 35-74 years of age, living in San Francisco
      and Alameda Counties, Calif. were used. A total of 798 Latinos (398 men and 408
      women) and 436 Anglos (214 men and 222 women) completed the interview. RESULTS:
      Age-adjusted rates showed that 82.0% of Latinas reported a Pap smear within 3
      years compared with 85.1% of Anglo women. A clinical breast examination within 2
      years was reported by 82.1% of Latinas and by 88.9% of Anglo women. Screening
      mammograms within 2 years were reported by 57.8% of Latinas and by 72.3% of Anglo
      women (difference = -14.5%; 95% confidence interval [CI] = -21.5, -7.5). Compared
      with Anglos, fewer Latinos reported digital-rectal examinations within 2 years
      (44.6% versus 61.8%; difference = -17.2%; 95% CI = -22.6, -11.8). There were no
      significant differences by ethnicity in obtaining a fecal occult blood test
      within 2 years (32.3% versus 34.0%) and sigmoidoscopy within 5 years (18.9%
      versus 21.5%). After adjusting for age, education, health insurance, employment,
      marital status, county of residence, and self-perceived health status, Latino
      ethnicity was a significant predictor only for digital-rectal examination within
      2 years (odds ratio [OR] = 0.65; 95% CI = 0.49-0.86) and digital-rectal
      examination ever (OR = 0.54; 95% CI = 0.40-0.74). Latinos were significantly more
      likely to cite forgetfulness, lack of transportation, long wait for appointments,
      and need for child care as reasons for not having cancer screening tests.
      CONCLUSION: We conclude that after accounting for socioeconomic factors, Latino
      ethnicity is a relatively minor predictor of use of cancer screening tests.
      Increasing the availability of culturally appropriate educational materials and
      providing universal health care coverage are more important priorities to promote
      appropriate use of cancer screening tests by Latinos.

PMID- 8562214
TI  - Por La Vida intervention model for cancer prevention in Latinas.
AB  - Our goal was to describe the development and implementation of an intervention on
      cancer prevention for Latinas in San Diego, Calif. Thirty-six lay community
      workers ("consejeras") were recruited and trained to conduct educational group
      sessions. Each consejera recruited approximately 14 peers from the community to
      participate in the program (total number = 512). Half of the consejeras were
      randomly assigned to a control group, in which they participated in an equally
      engaging program entitled "Community Living Skills." Implementation of the
      intervention was assessed by qualitative and quantitative methods.
      Preintervention and postintervention self-report information was obtained from
      project participants on access to health care services, cancer knowledge,
      preventive measures, and previous cancer-screening examinations. Base-line data
      suggest that lack of knowledge, costs of cancer-screening tests, and the lack of
      a regular health care provider are the major obstacles against obtaining cancer
      screening tests. Predisposing factors, such as fear and embarrassment, also
      constitute barriers to getting regular cervical cancer screening. Preliminary
      analysis indicates that the Por La Vida intervention increases use of cancer
      screening tests in comparison to a community living skills control group.
      Universal access to health care would remove some of the major financial barriers
      to cancer screening. The Por La Vida program attempts to overcome the substantial
      barriers by reaching out to low-income Latinas and by providing information
      regarding the availability, acceptability, and preventive nature of cancer
      screening tests.

PMID- 8562216
TI  - Effectiveness of disseminating culturally appropriate smoking-cessation
      information: Programa Latino Para Dejar de Fumar.
AB  - BACKGROUND: The need for a culturally appropriate smoking-cessation intervention
      for Latinos is based on data on current patterns of tobacco use, possible
      targeting by the tobacco industry, and the lack of smoking-cessation
      interventions that are appropriate to the cultural characteristics of Latino
      smokers. PURPOSE: Our goal was to evaluate the effectiveness of the Programa
      Latino Para Dejar de Fumar (PLDF) in disseminating smoking-cessation information
      in San Francisco's Latino community. METHODS: Annual cross-sectional telephone
      surveys were conducted from 1986 to 1993 of Latino adults, 18-65 years of age,
      living in census tracts with at least 10% Latinos. Surveys in 1986 and 1987
      formed the base line for comparison of PLDF effects. RESULTS: Awareness of a
      Hispanic smoking-cessation program (odds ratio [OR] = 1.11; 95% confidence
      interval [CI] = 1.09-1.14), awareness of PLDF specifically (OR = 1.14; 95% CI =
      1.10-1.17), awareness of available printed information to help smokers quit (OR =
      1.09; 95% CI = 1.06-1.12), and having a copy of the Guia Para Dejar de Fumar (OR
      = 1.09; 95% CI = 1.05-1.14) were significantly associated with year of survey. In
      addition, those same variables were significantly associated with a lower
      acculturation score (respective ORs = 3.95, and 95% CI = 3.57-4.37; OR = 5.40,
      and 95% CI = 4.86-6.01; OR = 0.63, and 95% CI = 0.58-0.69; and OR = 4.54, and 95%
      CI = 3.89-5.30). Women were more likely than men to report awareness of a
      Hispanic smoking-cessation program (OR = 0.88; 95% CI = 0.81-0.96), awareness of
      PLDF (OR = 0.84; 95% CI = 0.77-0.92), and awareness of available printed
      information (OR = 0.78; 95% CI = 0.72-0.85). Cigarette-smoking prevalence
      decreased from 1986 through 1990, stabilized in 1991, and appeared to increase
      among all groups in 1993. Prevalence of smoking cessation remained stable
      overall, but it showed a steady increase among less acculturated respondents.
      CONCLUSION: We conclude that a culturally appropriate community intervention to
      promote nonsmoking can be successful at disseminating information about smoking
      cessation. Latino community norms about smoking are evolving, leading to
      decreased social acceptability.

PMID- 8562217
TI  - Hispanic research: implications of the National Institutes of Health guidelines
      on inclusion of women and minorities in clinical research.
AB  - Researchers have new opportunities to increase Hispanic health research as a
      result of the requirements in the March 1994 National Institutes of Health (NIH)
      guidelines on inclusion of women and minorities (and their subpopulations) as
      subjects in the biomedical and behavioral research projects that NIH supports.
      These guidelines are summarized and their implications for research are discussed
      here. Investigators must include women and minorities in their research involving
      human subjects and also present outreach plans for recruitment and retention of
      Hispanic and other participants into this clinical research. When clinical trials
      are planned, they need to be designed to measure differences in intervention
      effect in subpopulations when warranted. Investigators are challenged to develop
      new studies to fill the gaps in our knowledge about how radical/ethnic/cultural
      factors affect health and disease in Hispanic subgroups. This knowledge is
      necessary for designing studies that are culturally sensitive, enroll appropriate
      numbers of Hispanic participants, and ensure that the benefits of the research
      are made available to the Hispanic community.

PMID- 8562218
TI  - Epidemiology of cancer among Hispanics in the United States.
AB  - BACKGROUND: There are very limited data on cancer among U.S. Hispanics. The data
      that are available seldom appear outside individual registry reports. Without
      coalescing and assessing such information, the epidemiology of cancer among
      Hispanics cannot be understood. PURPOSE: This article presents an overall view of
      the epidemiology of cancer among Hispanic populations in the United States.
      METHODS: Major types of cancer were reviewed from geographic areas with 1) large
      Hispanic/Latino populations and 2) population-based cancer registries that cover
      68% of the U.S. Hispanic population. Age-standardized rates, standardized rate
      ratios, and ranks of the top cancers are presented for Hispanics and non
      Hispanics by sex. RESULTS: Hispanic men had consistently lower rates of cancers
      of the lung, prostate, colon, rectum, and oral cavity as well as of melanoma and
      non-Hodgkin's lymphoma than non-Hispanic men. Among Hispanic men, higher rates
      were observed for cancers of the stomach, liver, and gallbladder. Compared with
      the rates in non-Hispanic women, Hispanic women had consistently lower rates of
      cancers of the breast, colon, rectum, endometrium, lung, ovary, and oral cavity,
      non-Hodgkin's lymphoma, and melanoma and higher rates of cancers of the uterine
      cervix, stomach, liver, and gallbladder. Perhaps more importantly, however, was
      that, within U.S. Hispanic populations, the top five sites of cancer for women
      were breast, colon, lung, cervix, and uterine corpus. For men, the top sites were
      usually prostate, lung, colon, stomach, and rectum. Furthermore, some geographic
      areas showed differences in the order of importance within these five sites,
      while in other areas, the top five cancers for Hispanic men included kidney and
      bladder cancers, liver cancer, and non-Hodgkin's lymphomas. For women, other
      leading cancers mentioned were ovarian cancer, non-Hodgkin's lymphoma, and
      gallbladder cancer. CONCLUSIONS: Hispanics had consistently lower rates of
      breast, lung, prostate, and colon cancers than non-Hispanics. In some geographic
      regions, however, differences in cancer incidence rates with respect to specific
      sites existed between the heterogenous Hispanic populations. Furthermore, the
      rankings demonstrated that, even if Hispanics have lower rates of the most common
      cancers than non-Hispanics, such sites are still the most important cancers among
      Hispanic populations. IMPLICATIONS: Cancer is a major problem among U.S. Hispanic
      populations. The information given in this article can be used to develop
      etiologic studies and cancer control interventions. Data limitations and
      recommendations for improving data quality are presented.

PMID- 8562219
TI  - Lung cancer, smoking patterns, and mutagen sensitivity in Mexican-Americans.
AB  - BACKGROUND: Mexican-Americans have lower age-adjusted lung cancer incidence rates
      than non-Hispanic whites and African-Americans. Since 87% of lung cancers are
      attributed to tobacco exposure, this difference could be explained partly by
      lower prevalence of cigarette smoking. However, only a fraction of exposed
      individuals will develop smoking-related cancer, and genetically determined
      differences in modulation of environmental exposures could also explain some of
      this ethnic risk differential in lung cancer incidence in the United States.
      However, little research on genetic susceptibility has been focused on Hispanic
      populations in the United States. METHODS: We are conducting a case-control study
      of lung cancer in a high-risk group (African-Americans) and a low-risk group
      (Mexican-Americans) to evaluate ethnic differences in mutagen sensitivity by an
      in vitro assay that quantifies mutagen-induced chromosome breaks in short-term
      lymphocyte cultures. RESULTS: In the 174 Mexican-Americans (67 lung cancer case
      patients and 107 control subjects) accrued to date, all measures of cigarette
      smoking (intensity, duration, nicotine and tar contents, depth of inhalation, and
      type of cigarette) were significant predictors of lung cancer risk. There were
      significantly higher risks associated with mutagen sensitivity (defined as > or =
      1 break/cell) for both former smokers (odds ratio [OR] = 4.5; 95% confidence
      interval [CI] = 0.9-21.9) and current smokers (OR = 2.6; 95% CI = 0.6-11.1).
      Mutagen sensitivity also appeared to be implicated in risk in patients who were
      less than 55 years old at diagnosis (OR = 15.0; 95% CI = 1.0-228.9) and in those
      with lower cigarette exposure (OR = 11.0; compared with an OR of 1.7 for the
      heaviest smokers). The overall OR for mutagen sensitivity adjusted for age, sex,
      and pack-years of smoking was 2.9 (95% CI = 0.8-9.9). Neither current smoking
      status nor years of exposure shifted the sensitivity profile of case patients and
      control subjects. CONCLUSION: Although this study showed higher percentages of
      nonsmokers among Mexican-Americans than our previously reported data for African
      Americans, the Mexican-American case patients were heavier smokers than the
      African-American case patients. The prevalence of mutagen sensitivity for Mexican
      Americans was 64.1% in case patients and 26.2% in control subjects. In African
      Americans, mutagen sensitivity was previously reported to be 55.3% in case
      patients and 24.6% in control subjects. These preliminary data do not support our
      a priori hypothesis that a lower prevalence of mutagen sensitivity in Mexican
      Americans would account for the lower incidence of lung cancer. Mutagen
      sensitivity, however, is only one of an array of potential susceptibility markers
      that we are evaluating in this unique population.

PMID- 8562220
TI  - Cancer in Hispanics: issues of concern.
AB  - Hispanics are among the fastest growing minorities in the United States, after
      Asian-Americans and Pacific-Islanders. Hispanics, Latinos, Chicanos, Mexican
      Americans, Puerto Ricans, Cuban-Americans, etc. are all designations used to
      describe this large, heterogeneous population with different cultural, ethnic,
      geographic, and social backgrounds. There is still no clear definition of the
      term "Hispanic." The data available regarding the incidence, morbidity, and
      mortality from cancer in Hispanics are scarce, scattered, outdated, and often
      incomplete. From the studies looking at the accessibility and availability of
      medical care for this population, few have examined in detail the variability
      within the entire Hispanic population. The aggregation of culturally distinct
      subgroups, which have resided in the United States for different periods of time,
      into a more inclusive Hispanic category assumes that all persons of Mexican,
      Cuban, and Puerto Rican extraction have similar needs and experience similar
      barriers in using health services. There is, however, no clear evidence for this
      assumption. On the contrary, there is evidence that each group has specific
      characteristics that make it different and independent from another, despite the
      fact that they also share some commonalities. Because of the lower overall
      prevalence of cancer in this population, potential protective factors need to be
      explored. Hispanics, however, appear to have a less favorable stage of disease at
      presentation and have overall lower death rates from cancer than non-Hispanic
      whites, but lower overall survival in certain cancers. Demographic and
      epidemiologic data collection need to be updated and improved.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8562221
TI  - Comparing acculturation scales and their relationship to cancer screening among
      older Mexican-American women.
AB  - BACKGROUND: Hispanic women in the United States are less likely to participate in
      breast and cervical cancer screening than women of other racial and ethnic
      groups. To plan appropriate interventions requires an understanding of the
      barriers to participation, including those of acculturation and assimilation. Few
      studies have examined the effects of acculturation and assimilation on the cancer
      screening behavior of Mexican-American women. PURPOSE: Because of the extensive
      use of the Cuellar acculturation scale and the more recent use of the Hazuda
      scale, we explore the utility of these two measures to predict Pap smear and
      mammography screening. Using a population-based sample of Mexican-American women
      aged 40 years and older, we compare the two scales with each other and describe
      their relationship to sociodemographic factors and to participation in cancer
      screening. METHODS: The data are from baseline surveys in El Paso and Houston,
      Tex., conducted before the implementation of community interventions to improve
      Pap smear and mammography screening in low-income Mexican-American women. Study
      subjects were 923 randomly selected Mexican-American women aged 40 years and
      older living in 16 El Paso census tracts and seven Houston census tracts.
      Personal interviews solicited information on age, martial and employment status,
      household annual income and size, education, health insurance coverage, Pap smear
      and mammogram history, and a series of acculturation dimensions. Acculturation
      was measured using the abbreviated version of the Cuellar scale developed for the
      Hispanic Health and Nutrition Examination Survey, 1982-1984, and the Hazuda scale
      developed for the San Antonio Heart Study. The eight-item Cuellar acculturation
      scale assessed the extent to which Spanish and English were spoken, preferred,
      read, and written; the ethnic identification of the respondent and her parents;
      and generational status in the United States. The Hazuda scale assessed the
      following dimensions of acculturation: adult proficiency in English, adult
      pattern of English versus Spanish language usage, value placed on preserving
      Mexican cultural origin, attitude toward traditional family structure and sex
      role organization, and adult interaction with members of mainstream society.
      RESULTS: The Cuellar scale was highly correlated with Hazuda's two language
      dimension. The Hazuda scale dimensions, Mexican cultural values and traditional
      family attitudes, correlated the least with Cuellar's scale. All the
      acculturation dimensions, Cuellar's and Hazuda's, were strongly associated with
      education and health insurance coverage. With the use of multiple logistic
      regression to adjust for education, health insurance, and other variables,
      English proficiency was a predictor of both a recent Pap smear and a recent
      mammogram. No other language-based acculturation dimension was associated with a
      recent screening with adjustment for education, health insurance, and other
      variables. However, in controlling for these factors, we found that a woman's
      attitude toward traditional family structure was related inversely to mammogram
      screening. That is, women who held the strongest traditional Mexican family
      attitudes were more likely to participate in mammography screening. CONCLUSION:
      This study shows the importance of separating the effects of acculturation on
      cancer screening from those due to social and economic conditions. Results
      suggest that the Hazuda scale provides a more multidimensional approach than the
      Cuellar scale and is a superior measure of the acculturation process. Traditional
      Mexican family attitudes positively influence mammogram-screening behavior, and
      this finding has implications for cancer control interventions in this
      population.

PMID- 8562222
TI  - Screening practices and knowledge, attitudes, and beliefs about cancer among
      Hispanic and non-Hispanic white women 35 years old or older in Nueces County,
      Texas.
AB  - A telephone survey was conducted among women 35 years old or older in Nueces
      County, Tex., to assess ethnic differences between Hispanic and non-Hispanic
      white women in self-reported cancer-screening practices and knowledge, attitudes,
      and beliefs about cancer and to evaluate the effect of ethnicity as a predictor
      for screening practices. A total of 233 Hispanic and 332 non-Hispanic white women
      participated in the survey. Hispanics were younger and had lower educational and
      income levels. Overall, Hispanics had lower rates than did non-Hispanics of
      lifetime mammography (65% versus 79%), clinical breast examination (86% versus
      96%), monthly performance of breast self-examination (37% versus 49%), and
      lifetime fecal occult blood testing (36% versus 69%). After control for
      confounding factors, Hispanics were still less likely to have ever had a clinical
      breast examination and fecal occult blood test. Our results suggest the need for
      more culturally sensitive health promotion efforts to improve knowledge about
      cancer and early detection practices among Hispanic women.

PMID- 8562223
TI  - Beliefs, knowledge, and behavior about cancer among urban Hispanic women.
AB  - As part of a cancer prevention program aimed at minority and disadvantaged urban
      women, cancer beliefs, knowledge, and behaviors were assessed among home-health
      attendants in the Bronx, N.Y. Information, was gathered from 876 Hispanic women
      who comprised 62% of the female home-attendant study population from whom data
      were collected (n = 1413). Of these women, 82% (n = 718) were Spanish speaking
      and 18% (n = 158) were English speaking as defined by their choice to complete
      the survey questionnaire in Spanish or English. As a whole, the population
      reported high levels of obtaining screening tests and engaging in preventive
      behaviors. However, nearly 60% did not know what cervical cancer was. The most
      important predictor of inadequate cancer screening was lack of knowledge. Large
      numbers of women subscribed to cancer misconceptions, such as the belief that
      bumps or bruises cause cancer. Fifty-eight percent believed that surgery causes
      cancer to spread, a belief that may prevent a woman with breast cancer from
      undergoing early intervention procedures, such as lumpectomy. This survey
      indicated that Hispanic women in our population engaged in relatively high levels
      of cancer preventive behaviors, even though their knowledge base was limited.
      Many of them hold misperceptions about cancer that can have an impact on
      preventive behaviors. We conclude that cancer prevention programs targeting the
      Hispanic populations should emphasize the provision of factual information about
      cancer and cancer-screening behaviors in the context of an exploration of
      inaccurate beliefs about cancer that may inhibit preventive health behaviors.

PMID- 8562224
TI  - Psychosocial correlates of smoking among immigrant Latina adolescents.
AB  - Young immigrant Latinas, compared with non-Latina white adolescents, are at
      greater risk to begin smoking and experimenting with other substances; yet little
      is known about the contributing factors that place them at this risk. To identify
      psychosocial predictors of smoking, a sample of 447 self-identified Latinas and
      160 non-Latina white adolescents aged 13-18 years from San Francisco and San
      Mateo counties, Calif., answered a 30-minute face-to-face questionnaire.
      Significant predictors of smoking status for the entire sample were (a) self
      efficacy to avoid smoking (odds ratio [OR] = 10; 95% confidence interval [CI] = 5
      21; P < .001), (b) intention to smoke even if it is risky (OR = 10; 95% CI = 5
      20; P < .001), (c) usage of free time (OR = 4; 95% CI = 2-8; P < .001), (d)
      personal approval of others' smoking (OR = 3; 95% CI = 1-5; P < .01), and (e)
      peer's smoking approval (OR = 2; 95% CI = 1-4; P < .05). The majority of the
      adolescent smokers in this study reported low levels of self-efficacy for
      avoiding smoking and believed that they would continue to smoke even if it was
      risky. They spent more of their free time with friends or alone, reported higher
      personal approval of significant others' smoking, and reported stronger perceived
      peer's approval of smoking than nonsmokers. For non-Latina whites, personal
      approval of others' smoking and having serious problems were associated with
      smoking.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562226
TI  - Role of cigarette smoking as a gateway drug to alcohol use in Hispanic junior
      high school students.
AB  - BACKGROUND: Many studies have examined predictors of alcohol and other substance
      use in adolescents, but few have looked specifically at Hispanic adolescents in
      their junior high school years. PURPOSE: The purpose of this study was to explore
      the extent to which tobacco use may contribute as a gateway drug for subsequent
      alcohol use among Hispanic adolescents in San Diego, Calif. METHODS: A multiple
      regression procedure was used to test if 7th-grade to 9th-grade change in smoking
      status predicted 9th-grade alcohol use while controlling for a variety of other
      variables. RESULTS: Among the variables analyzed, increased level of smoking was
      the strongest predictor of subsequent 9th-grade alcohol use, followed by stronger
      intentions to drink, female sex, and having grades below a "C." CONCLUSION: 7th-
      to 9th-grade smoking change is highly predictive of subsequent alcohol use.
      IMPLICATIONS: The study findings suggest that preventive intervention for alcohol
      use among Hispanic adolescents should focus on changes in smoking status as a
      significant risk factor and should examine the role of acculturation and other
      variations that make this population different from other U.S. subgroups.

PMID- 8562225
TI  - Dietary practices, alcohol consumption, and smoking behavior: ethnic, sex, and
      acculturation differences.
AB  - Current knowledge is scarce on Latino dietary practices. This study compared the
      dietary practices, alcohol consumption, and smoking behavior of Latinos and non
      Latino whites in two randomly selected samples. Telephone surveys of adults 35-74
      years of age from the Kaiser Permanente Medical Care Program (Latinos = 844; non
      Latino whites = 510) and from census tract-based areas (Latinos = 806; non-Latino
      whites = 436) were conducted in the San Francisco Bay Area. Latino ethnicity was
      a significant predictor of dietary and alcohol consumption practices in
      multivariate logistic regression models after adjustment for sex, education, age,
      employment, health insurance, martial status, county of residence, and self
      perceived health status. Compared with non-Latino whites, Latinos were
      significantly less likely to report eating vegetables and more likely to eat
      rice, beans, and fried foods and to drink whole milk. Less acculturated Latinos
      were more likely to eat fruits, rice, beans, meat, and fried foods and to drink
      whole milk than more acculturated Latinos. Latino men were significantly more
      likely to be binge drinkers, and Latina women were significantly more likely to
      abstain from drinking alcohol during the month prior to the interview. As Latina
      women acculturate to the U.S. mainstream, they report more cigarette smoking and
      alcohol consumption. Although Latinos reported higher levels of selected high
      fiber foods, the low consumption of vegetables, widespread use of saturated fat,
      and the heavy drinking and smoking among Latino men, which are associated with
      the level of acculturation, may increase the risk for cancer. Educational
      messages targeting less acculturated Latinos should focus on maintaining their
      current healthy dietary practices of eating fruits, rice, and beans and
      decreasing their fat consumption. For more acculturated Latinos, emphasis should
      be placed on resuming the traditional diet.

PMID- 8562227
TI  - Latino male attitudes and behaviors on their spouses' and partners' cancer
      screening behavior: focus group findings.
AB  - The following is a report of the first phase of exploratory research growing out
      of a parent grant on breast and cervical cancer screening among Latinas in
      Colorado. This paper reports data gathered from 14 focus groups conducted with
      Latino (Mexican, Mexican-American, and other Hispanic) males to identify their
      supportive and nonsupportive attitudes and behaviors toward their spouse's breast
      and cervical cancer screening. The men represent a cross-section of Latino males,
      yet the findings presented here are strongly suggestive and not representative of
      Latinos as a whole. Latinos exhibited three distinct modes of knowledge and
      attitudes toward their partners' health-seeking efforts. The first mode was
      characterized by limited knowledge, a lack of information, and for some,
      disinterest or even disdain. Those in the second mode can be considered
      "generalists" who knew only generalities concerning their wives' health states
      and practices. The third mode includes Latino males who were genuinely interested
      in seeking "meaningful ways" to promote their partners' health and well-being.
      These long-time married couples seemed to have strong relationships highlighted
      by a genuine concern for each others' well-being, including their health
      problems. The younger cohorts were generally unconcerned about their spouses'
      breast and cervical cancer screening and lacked knowledge in the area. As age and
      educational level increased, so too did the general awareness and knowledge of
      breast and cervical cancer increase. Most Latinos, however, lacked specific
      knowledge about screening, the procedures, or the recommended frequency of such
      examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562228
TI  - Attitudes of Colorado health professionals toward breast and cervical cancer
      screening in Hispanic women.
AB  - BACKGROUND: A variety of economic, cultural, and communication barriers appear to
      be involved in breast and cervical cancer screening among Hispanic women. These
      barriers include culture-based embarrassment both for mammography and for Pap
      smears and fear and hopelessness concerning a diagnosis of cancer. Cost and
      access barriers are shared by low-income women from various ethnic and racial
      groups, as is a purported lack of physician referral. Hispanic women may have the
      latter problem enhanced by a language barrier between physicians and patients
      when the physicians do not speak or understand Spanish. PURPOSE: The goal of this
      project, conducted by the Cancer Education Division of the University of Colorado
      Cancer Center, has been to determine the attitudes and practices among health
      care providers in areas of Colorado with relatively large Hispanic populations
      (concerning screening mammography, clinical breast examination, breast self
      examination, and Pap testing) and to design interventions to address any
      deficiencies or problems recognized. These studies were coordinated with
      telephone surveys and focus groups involving Hispanic women, directed by E.
      Flores in the Department of Sociology of the University of Colorado at Boulder
      and by C. Chrvala at the Colorado Department of Health. METHODS: Data were
      collected from 520 primary care physicians, nurses, and allied health personnel
      in 11 Colorado counties through focus groups and mailed questionnaires. Responses
      were analyzed by considering a variety of demographic characteristics of the
      respondents and by stratifying the associated practices by percent of Hispanic
      patients. RESULTS: The physicians involved in the focus groups and responding to
      the questionnaires, as well as their associated nurses and other health care
      personnel, are generally familiar with the breast and cervical cancer-screening
      guidelines as developed and disseminated by several organizations, including the
      National Cancer Institute and the American Cancer Society. Major barriers to
      screening Hispanic women, as perceived by these health care providers, appear to
      be cost; lack of transportation, child care, and release from work; fear of
      diagnosis of cancer; patients considering the test unnecessary; discomfort; and
      embarrassment. The prompt use of colposcopy to evaluate patients whose Pap smears
      indicated dysplasia appeared less than optimal, especially among internists.
      CONCLUSIONS: Familiarity with guidelines for breast and cervical cancer screening
      is widespread among Colorado physicians and associated health care personnel,
      including those with high percentages of Hispanic patients in their practices.
      Increased continuing education efforts may be indicated concerning the
      application of colposcopy to the evaluation of women with abnormal Pap smears and
      concerning the application of computer technology to cancer-screening reminder
      systems. IMPLICATIONS: Educational approaches to primary care professionals may
      improve the effectiveness of breast and cervical cancer screening, although a
      variety of other approaches will also be necessary to decrease barriers to
      screening of Hispanic women.

PMID- 8562229
TI  - Non-surgical ablation of the ventricular septum for the treatment of hypertrophic
      cardiomyopathy.

PMID- 8562230
TI  - How should we manage symptomatic aortic stenosis in the patient who is 80 or
      older?

PMID- 8562231
TI  - New concepts for interpretation of intracoronary velocity and pressure tracings.
AB  - The development of quantitative angiography and the introduction of new imaging
      techniques cannot replace functional methods of assessing the severity of
      stenosis. Measurement of transstenotic pressure gradient and poststenotic flow
      velocity using miniaturised sensors with guidewire technology offers an
      alternative to the conventional non-invasive methods that is immediately
      applicable in the catheterisation laboratory during interventional procedures.
      The complexity of the coronary circulation, however, makes it difficult to
      establish simple cut-off criteria to identify the presence of a flow-limiting
      stenosis. For intermediate lesions or in the presence of variable haemodynamic
      conditions, the accuracy of the assessment can be improved by the application of
      more complex indices proposed and validated in the laboratory animals. Two of
      these indices are myocardial fractional flow reserve and the slope of the
      instantaneous relation between pressure or pressure gradient and flow velocity.

PMID- 8562232
TI  - Reduced in-hospital mortality from acute myocardial infarction with general
      adoption of thrombolytic treatment in the North West Thames health region 1979
      1991.
AB  - OBJECTIVE: To determine the impact of studies of thrombolytic treatment in acute
      myocardial infarction on inhospital mortality. DESIGN: Retrospective study.
      SETTING: All 21 major hospitals in the North West Thames health region. PATIENTS:
      63,903 patients with acute myocardial infarction. STUDY PERIOD: 1979-1991. MAIN
      OUTCOME MEASURES: in-hospital mortality. RESULTS: Overall mortality decreased by
      5.2% from 25.4% to 20.2% (P < 0.0001) (95% confidence interval (CI) 3.4 to 6.6).
      Male mortality decreased by 6.5% from 22.3% to 15.8% (P < 0.0001) (95% CI 4.8 to
      8.4); female mortality decreased by 4.3% from 32.6% to 28.3% (P < 0.01) (95% CI
      1.3 to 7.4). Reductions in mortality occurred in all age and sex groups but were
      greater in younger patients. Logistic regression analysis of death rates showed
      that the odds ratio of death in 1991 compared with that in 1979 was 0.75 (95% CI
      0.69 to 0.82). After allowing for the effects of age and sex, this odds ratio
      became 0.54 (95% CI 0.49 to 0.59), as more elderly patients were treated in 1991.
      Purchase of streptokinase increased 31-fold from 116 doses in 1983 to 3554 doses
      in 1991. There was a pronounced negative association between annual purchases of
      streptokinase and mortality (Kendall's rank correlation = -0.86, P = 0.003).
      Changes in clinical practice resulted in the saving of the lives of an estimated
      600 patients with acute myocardial infarction in 1991. This extrapolates to an
      annual saving of 10,500 lives in the United Kingdom. CONCLUSIONS: In the past few
      years thrombolytic treatment has been widely adopted for the management of acute
      myocardial infarction. This has been paralleled by a substantial reduction in in
      hospital mortality.

PMID- 8562233
TI  - Helicobacter pylori infection: relation with cardiovascular risk factors,
      ischaemic heart disease, and social class.
AB  - OBJECTIVE: To determine whether Helicobacter pylori infection is associated with
      the development of ischaemic heart disease and whether such infection can explain
      the social class inequality in ischaemic heart disease. DESIGN: Cardiovascular
      risk factor levels, prevalence of ischaemic heart disease (Rose questionnaire
      angina, and/or a history of myocardial infarction), and serum antibodies to H
      pylori (enzyme linked immunosorbent assay) were assessed in a cross sectional
      population based survey. SETTING: Belfast and surrounding districts, Northern
      Ireland. PARTICIPANTS: 1182 men and 1198 women aged 25-64 years randomly selected
      from the Central Services Agency's general practitioner lists. MAIN OUTCOME
      MEASURES: The relation of H pylori infection with cardiovascular risk factors and
      ischaemic heart disease. The association of social class with ischaemic heart
      disease. RESULTS: Systolic and diastolic blood pressure, plasma viscosity, and
      total cholesterol were not associated with H pylori infection. A weak negative
      association existed between H pylori infection and fibrinogen (mean (SE)
      difference in fibrinogen between infected and uninfected individuals -0.09 (0.04)
      g/l, P = 0.02) and between infection in women and high density lipoprotein (HDL)
      cholesterol (mean (SE) difference in HDL cholesterol between infected and
      uninfected individuals -0.06 (0.02) mmol/l, P = 0.006). A potentially important
      association was demonstrated between H pylori infection and ischaemic heart
      disease but this did not reach statistical significance (odds ratio (95%
      confidence interval (CI) 1.51 (0.93 to 2.45), P = 0.1). Social class was
      associated with ischaemic heart disease independently of cardiovascular risk
      factors and H pylori infection (odds ratio, manual v non-manual (95% CI) 1.82
      (1.14 to 2.91), P = 0.01). CONCLUSION: H pylori may be independently associated
      with the development of ischaemic heart disease but if this is so the mechanism
      by which this effect is exerted is not through increased concentration of plasma
      fibrinogen. H pylori infection does not explain the social class inequality in
      ischaemic heart disease which exists independently of known cardiovascular risk
      factors.

PMID- 8562234
TI  - Effect of low dose beta blockers on atrial and ventricular (B type) natriuretic
      factor in heart failure: a double blind, randomised comparison of metoprolol and
      a third generation vasodilating beta blocker.
AB  - OBJECTIVES: This study examines the acute effects of two differing beta
      adrenergic blocking agents (metoprolol and a third generation vasodilating beta
      blocker) on plasma concentrations of atrial natriuretic factor (ANF), brain
      (ventricular) natriuretic factor (BNF), and haemodynamic variables in patients
      with heart failure. SETTING: University teaching hospital. METHODS: 20 patients
      with impaired left ventricular systolic function [ejection fraction 32 (SEM
      2.3)%] were randomised in a double blind manner to receive either oral metoprolol
      6.25 mg twice daily or celiprolol 25 mg daily. Haemodynamic variables were
      evaluated by Swan-Ganz pulmonary artery catheter over 24 hours. ANF and BNF
      concentrations were measured at baseline, 5 h, and 24 h by radioimmunoassay.
      RESULTS: At baseline ANF and BNF concentrations were considerably raised compared
      to the normal range. Treatment with metoprolol caused ANF to rise further to 147%
      of the basal level at 5 h (P = 0.017) and 112% at 24 h (P = 0.029). This was
      associated with a small but non-significant rise in pulmonary capillary wedge
      pressure. Cardiac output and systemic vascular resistance were unchanged at 24 h.
      In contrast, after celiprolol ANF fell to 90% of basal levels at 5 h and to 74%
      of basal level at 24 h (P = 0.019), associated with a small but non-significant
      fall in pulmonary capillary wedge pressure [-3.3 (2.7) mm Hg] and systemic
      vascular resistance, and rise in cardiac output from 3.2 (0.2) to 4.0 (0.4) l/min
      (P = 0.04). BNF concentrations rose to 112% of baseline at 5 h (P = 0.09) after
      metoprolol but fell slightly, to 91% of baseline values, after celiprolol (NS).
      CONCLUSIONS: Metoprolol, even in very low doses (6.25 mg), produced a rise in ANF
      and BNF, although minimal haemodynamic changes were detected. In contrast, a
      vasodilating beta blocker was associated with a significant fall in ANF and BNF
      and a small rise in cardiac output. This study confirms both the advantages of
      vasodilating beta blockers over metoprolol for initial treatment of heart failure
      and the usefulness of ANF and BNF measurements for the assessment of drug effects
      in heart failure compared to traditional haemodynamic measurements.

PMID- 8562235
TI  - Left ventricular chamber dilatation in hypertrophic cardiomyopathy: related
      variables and prognosis in patients with medical and surgical therapy.
AB  - BACKGROUND: To determine the incidence and prognosis of left ventricular
      dilatation and systolic dysfunction in 139 patients with hypertrophic
      cardiomyopathy during long term follow up. METHODS: Left ventricular chamber
      dilatation and systolic dysfunction (both together referred to as left
      ventricular chamber dilatation) were determined echocardiographically. Chamber
      dilatation was defined as an increase in the left ventricular end diastolic
      diameter of > 2% per year combined with a decrease in midventricular systolic
      fractional shortening of > 2% per year of follow up [10.3 (SD 6) years]. The
      predictive value for left ventricular chamber dilatation of clinical, invasive,
      and echocardiographic variables and its prognosis were assessed. RESULTS: In 119
      of 139 individuals (86%), left ventricular chamber size and systolic function
      remained stable (group 1), and in 20/139 patients (14%) left ventricular chamber
      dilatation occurred during follow up (group 2). At baseline examination, symptoms
      such as dyspnoea and syncope occurred less often in group 1 than in group 2; New
      York Heart Association classification was lower in group 1 than in group 2 (P =
      0.001). Left ventricular mass index relative to sex specific normal values was
      increased by 18% in group 1 and by 41% in group 2 (P = 0.04). Cumulative survival
      rates were slightly although not significantly higher in group 1 than in group 2.
      Event-free survival was significantly higher in group 1 than in group 2 (P <
      0.05). CONCLUSIONS: (1) The development of left ventricular chamber dilatation
      and systolic dysfunction in hypertrophic cardiomyopathy occurs in approximately
      1.5% of the patients per year. (2) Factors associated with left ventricular
      dilatation are dyspnoea, syncope, a higher functional classification, and a
      higher degree of left ventricular hypertrophy. (3) Patients with chamber
      dilatation have a worse prognosis than those without, particularly regarding
      quality of life.

PMID- 8562238
TI  - Images in cardiology. Hypertrophic cardiomyopathy.

PMID- 8562236
TI  - Evidence that continuous normothermic blood cardioplegia offers better myocardial
      protection than intermittent hypothermic cardioplegia.
AB  - OBJECTIVES: To compare transmyocardial ischaemia and oxidative stress, as well as
      non-infarction myocardial injury, in patients randomised to intermittent
      hypothermic cardioplegia or continuous normothermic blood-potassium cardioplegia.
      DESIGN: Prospective randomised trial. SETTING: Tertiary cardiac referral centre.
      METHODS: 24 patients undergoing elective coronary artery bypass surgery were
      randomised to hypothermic (13 patients, mean (SEM) age 59.5 (2.6) years) or
      normothermic (11 patients, mean (SEM) age 59.7 (3.3) years) cardioplegia.
      Transmyocardial oxidative stress and ischaemia were assessed by the difference in
      plasma concentrations of oxidised glutathione and lactate respectively, from
      samples taken simultaneously from the coronary sinus and aortic root. Blood
      samples were taken just before cross clamp application and at intervals up to 15
      min after cross clamp release. Non-infarction myocardial injury was assessed by
      measurement of creatine kinase MB isoenzyme activity from peripheral venous blood
      taken 2 and 18 h after surgery. RESULTS: Intermittent hypothermic cardioplegia
      resulted in a significant increase in transmyocardial ischaemia (P < 0.001) and
      oxidative stress (P < 0.001). Evidence of significantly increased myocyte damage
      was also present (P < 0.01). No significant corresponding changes were present
      with normothermic cardioplegia. CONCLUSIONS: Normothermic blood cardioplegia
      seems to avoid significant changes in myocardial ischaemic status and consequent
      oxidative stress. This study provides direct evidence that normothermic
      cardioplegia offers enhanced myocardial protection compared with that of
      hypothermic cardioplegia. Certain subsets of patients may derive more benefit
      from normothermic cardioplegia, although it is unclear whether this would be the
      case for all patients.

PMID- 8562237
TI  - Molecular detection and serotypic analysis of enterovirus RNA in archival
      specimens from patients with acute myocarditis.
AB  - OBJECTIVE: To determine whether enterovirus RNA can be demonstrated in archival
      necropsy material in acute myocarditis. DESIGN: Analysis of paraffin embedded
      myocardial tissue from cases of acute myocarditis. SETTING: University virology
      department. METHODS: Extraction of RNA from tissue followed by polymerase chain
      reaction (PCR) and DNA sequence analysis. PATIENTS: Six patients with
      histologically proven myocarditis and eight controls. RESULTS: Enterovirus RNA
      was identified in 5 of 6 patients with myocarditis and in none of the controls.
      The nucleotide sequences of the PCR products showed greatest similarity to group
      B coxsackieviruses, particularly coxsackievirus B3. CONCLUSION: This study
      indicates that archival tissue samples, even histologically stained tissue
      sections, can be used to study the role of enteroviruses in myocardial disease
      using molecular detection techniques. If a predominant role for coxsackievirus B3
      in myocarditis is confirmed by further study, this may have implications for the
      development of a specific vaccine.

PMID- 8562239
TI  - Assessment of the severity of coronary artery disease at postmortem examination.
      Are the measurements clinically valid?
AB  - OBJECTIVE: To compare the assessment of severity of coronary artery stenosis by
      the conventional pathology methods with a method designed to resemble
      quantitative angiography. DESIGN: 31 human hearts harvested at necropsy were
      fixed by perfusion of the aortic root with 10% formol saline at 120 mm Hg for 24
      hours. The right coronary and left anterior descending coronary arteries were
      transversely sliced every 2 mm and the absolute lumen dimensions plotted against
      the distance from the coronary ostium. Stenosis figures were calculated by
      comparing the lumen diameter with the lumen diameters in adjacent normal arterial
      segments in a manner identical to that used in angiographic measurement. The
      coronary artery segments were then processed histologically. Stenosis was then
      remeasured by comparing the lumen diameter with the diameter of the vessel within
      the internal elastic lamina identified by elastic van Gieson staining. RESULTS:
      Compared with the method that was analogous to angiography, the pathology method
      used on histological slides overestimated the degree of stenosis by 25-30%. The
      lack of concordance between the methods was not a function of the severity of the
      stenosis. CONCLUSION: When they read necropsy reports in which the severity of
      coronary artery stenosis is assessed cardiologists should be aware of the
      discrepancy between clinical and pathological methods.

PMID- 8562240
TI  - M mode and Doppler echocardiographic assessment of left ventricular diastolic
      function in primary antiphospholipid syndrome.
AB  - BACKGROUND: High titres of serum antiphospholipid antibodies are a possible
      pathogenic factor for cardiac lesions in patients with systemic lupus
      erythematosus. OBJECTIVE: To test the hypothesis of a causal link between high
      titres of antiphospholipid antibodies in the serum and myocardial involvement in
      patients without systemic lupus erythematosus. PATIENTS AND DESIGN: 18 patients
      with primary antiphospholipid syndrome (recurrent fetal loss, arterial and/or
      venous thrombosis, high titres of antiphospholipid antibodies, and no criteria
      for systemic lupus erythematosus) were prospectively studied by cross sectional,
      M mode, and pulsed Doppler echocardiography, and compared with 18 healthy
      controls. The pulsed Doppler indices of left ventricular diastolic function
      included isovolumic relaxation time and four mitral outflow indices: peak
      velocity of early flow, peak velocity of late flow, early to late peak flow
      velocity ratio, and rate of deceleration of early flow. Four computerised M mode
      indices were also measured: peak rate of left ventricular enlargement in
      diastole, peak rate of posterior wall thinning, peak velocity of lengthening of
      the posterior wall, and velocity of circumferential chamber lengthening. RESULTS:
      Compared with controls, patients with primary antiphospholipid syndrome had
      higher values for isovolumic relaxation time and peak velocity of late mitral
      outflow and lower values for early to late mitral peak outflow velocity ratio,
      rate of deceleration of early mitral outflow, peak rate of left ventricular
      enlargement in diastole, peak rate of posterior wall thinning, peak velocity of
      lengthening of the posterior wall and velocity of circumferential chamber
      lengthening. CONCLUSION: This abnormal pattern reflects an impairment of
      myocardial relaxation and filling dynamics of the left ventricle in patients with
      primary antiphospholipid syndrome who were free of any clinically detectable
      heart disease. These data suggest that high serum titres of antiphospholipid
      antibodies may be associated with subclinical myocardial damage.

PMID- 8562241
TI  - Non-invasive detection of left atrial mechanical failure in patients with left
      ventricular disease.
AB  - OBJECTIVE: To define patients with left atrial mechanical failure and identify
      its echocardiographic, physiological, and clinical associations. DESIGN:
      Prospective study with cross sectionally guided M mode and Doppler
      echocardiograms, and with apexcardiograms, electrocardiograms, and
      phonocardiograms. SETTING: Tertiary cardiac referral centre. PATIENTS: 10
      patients with left atrial mechanical failure and 20 healthy controls of similar
      age. RESULTS: 10 patients with left atrial mechanical paralysis were identified
      among 4036 adults over a 1 year interval. Nine were in sinus rhythm and one had a
      DDD pacemaker. Left atrial mechanical activity was absent on M mode
      echocardiograms of the left sided atrioventricular ring and the aortic root. A
      Doppler A wave on transmitral flow and a clearly defined A wave on the left
      ventricular apexcardiogram were also absent, though evidence of right atrial
      mechanical movement was present in nine patients. Mean (SD) age was 63 (19) years
      and six were men. Nine had left ventricular disease and one had undergone
      extensive resection of the left atrium. Abnormal measurements of left ventricular
      end diastolic dimension (62 (13) mm), fractional shortening (15 (6)%), isovolumic
      relaxation time (19 (12) ms), left atrial size (45 (10) mm), and transmitral
      Doppler E wave deceleration time (110 (35) ms) were recorded. CONCLUSION: Left
      atrial mechanical failure may be present in patients with left ventricular
      disease despite normal sinus rhythm. Normal atrial activation on 12 lead
      electrocardiogram suggests it is primarily mechanical in origin. The possibility
      of left atrial mechanical failure must be considered when Doppler patterns of
      transmitral flow are used to assess left ventricular diastolic function.

PMID- 8562242
TI  - Images in cardiology. Infective endocarditis.

PMID- 8562243
TI  - Atrial thrombi occurring during sinus rhythm in cardiac amyloidosis: evidence for
      atrial electromechanical dissociation.
AB  - Thrombus formation in the left atrium is rare in patients in sinus rhythm. In
      three patients with extensive cardiac amyloidosis transthoracic echocardiography
      showed large atrial thrombi in or protruding into the body of the left atrium
      during sinus rhythm. Doppler studies showed no A wave on mitral inflow. Severe
      atrial and ventricular infiltration by amyloid may have resulted in mechanical
      atrial standstill with resultant thrombus formation. These findings suggest that
      patients with severe cardiac amyloidosis may require anticoagulation when atrial
      function is impaired.

PMID- 8562244
TI  - Aortic valve regurgitation caused by blunt chest injury.
AB  - Aortic valve regurgitation is an uncommon consequence of closed chest injury. It
      is caused by damage to the valve apparatus (ruptured cusp) or when subadventitial
      rupture of the ascending aorta causes prolapse of a subjacent valve cusp. Aortic
      valve regurgitation was detected in 4 patients (2 men and 2 women, 30 to 65 years
      old) who had sustained multiple injuries in road accidents 1 week to 30 years
      before. Three had subadventitial rupture of the ascending aorta and one had
      isolated rupture of the noncoronary cusp of the aortic valve. The mechanism
      responsible for the damage was believed to be a consequence of multiple chest
      lesions (right costal flap, sternal fracture, pulmonary contusion). It is
      difficult to diagnose and treat aortic regurgitation in patients with multiple
      injuries. Three patients had repair operations and the remaining patient needed
      valve replacement. If aortic regurgitation is haemodynamically well tolerated,
      the operation should be postponed until the patients have recovered from their
      other injuries. The results in these 4 patients and in other reported cases
      indicate that operations can be performed soon after the acute phase.

PMID- 8562245
TI  - Right to left interatrial communications after the modified Fontan procedure:
      identification and management with transcatheter occlusion.
AB  - OBJECTIVE: To describe unusual venous communications from the right to the left
      atrium resulting in cyanosis after the modified Fontan procedure, and their
      management with transcatheter occlusion. METHODS: Between September 1992 and
      November 1994, eight patients were assessed for persistent cyanosis after a
      modified Fontan procedure. Desaturation was found to be caused by unusual venous
      shunts originating at atrial level, and transcatheter occlusion with either a
      double umbrella or coil was attempted. RESULTS: Three types of venous channels
      were identified. The first type of communication consisted of thin long tortuous
      channels originating from the right atrial wall, and draining into the left
      atrium through a capillary network. The second type of communication was in the
      superior anterior portion of the atrial baffle, incorporating the pectinate
      muscles of the right atrium, draining into the neoleft atrium. These channels
      were shorter and often fanned out into small vessels toward the right atrial
      appendage. In each instance, the shunts were in the superior suture line of a
      lateral tunnel modification of the Fontan procedure. The third type of
      communication originated from the inferior vena cava, connecting inferior phrenic
      veins to pericardial veins and subsequently to the left atrium, at or close to
      the ostium of the left pulmonary veins. Before device occlusion, the room air
      aortic oxygen saturation was 88(SD 4)% (range 84% to 94%), and increased to
      95(3)% (range 91% to 100%) following occlusion (PL << 0.001). The mean right
      atrial pressure was 14(4)mm Hg and remained unchanged after occlusion. In six
      patients there was complete shunt obliteration, while in two both occluded with
      umbrella devices, a small residual leak persisted. No complication occurred
      during or immediately after catheterisation. CONCLUSIONS: Unusual venous
      communications can evolve after the Fontan procedure, resulting in the
      development or persistence of cyanosis. Some of these communications may be
      present preoperatively as normal veins draining into the right atrium, enlarging
      with the increased atrial pressure after surgery. These observations affect long
      term function after the Fontan procedure. Transcatheter occlusion of these
      communications is technically feasible and effective, although recurrence may
      occur.

PMID- 8562246
TI  - Electrophysiological properties of dual atrioventricular nodes in patients with
      right atrial isomerism.
AB  - There are reports that in right atrial isomerism the conduction system has paired
      sinus nodes and paired atrioventricular nodes. Electrophysiological studies were
      performed in two patients with right atrial isomerism. One patient had a delta
      wave on the surface electrocardiogram without tachycardia attacks. The other, who
      did not have manifest pre-excitation, had recurrent narrow QRS tachycardia.
      Electrophysiological studies suggested the presence of dual atrioventricular
      nodes. Only unidirectional atrioventricular or ventriculoatrial conduction was
      demonstrated for these dual atrioventricular nodes even after infusion of
      isoprenaline. It is suggested that unidirectional conduction may be a common
      property of the dual atrioventricular nodes in right atrial isomerism and that
      the absence of retrograde ventriculoatrial conduction protects the patients
      against tachycardia.

PMID- 8562247
TI  - In-hospital audit underestimates early postoperative morbidity after cardiac
      surgery.
AB  - BACKGROUND: The demand for open heart surgery has driven current practice towards
      early postoperative discharge and interhospital transfer to maximise patient
      throughput. The extent to which this redirects morbidity to other healthcare
      providers is unknown. OBJECTIVE: To define the incidence of inhospital and early
      postoperative morbidity within 6 weeks of primary hospital discharge after
      cardiac surgery. DESIGN: Prospective inhospital data for 322 consecutive adult
      patients undergoing cardiac surgery were compared with retrospective information
      obtained by postal questionnaire. RESULTS: Mean (SD) primary postoperative
      hospital stay was 8.3 (3.1) days. There were 13 inhospital deaths (4%), and three
      patients died within 6 weeks of primary discharge. Retrospective information was
      obtained from 297 patients (96%). Of these, 77% patients were discharged home
      directly, while 23% were transferred to other hospitals for continued medical
      care. Mean (SD) hospital stay after transfer was 12 (8.4) days and required 741
      additional hospital bed days. Thirty nine patients (13%) were readmitted to
      hospital, requiring a further 275 hospital bed days. The readmission rate was
      lower in patients sent home directly (10%), than in those who were transferred
      (22%; P < 0.001). CONCLUSIONS: Inhospital audit underestimates early morbidity
      after cardiac surgery. The burden transferred to other healthcare providers is
      considerable and has important financial implications for purchasers.

PMID- 8562248
TI  - Displaying the long-term progression of patients with coronary artery disease.
AB  - Cardiac clinicians are often faced with the problem of trying to assimilate
      details of a patient's long-term history. Case notes are often lengthy, making
      this process difficult if not impossible in the time available during an
      outpatient examination. A computer system has been developed to assist with this
      task. This generates a graphical summary of the principal features of a patient's
      long-term progression. It gives an overview of how the patient's anginal status
      has changed, his or her drug treatment and any surgical interventions. The system
      also allows the clinican to display summaries of diagnostic tests carried out.
      The system can be used to assist clinical management and speed up outpatient
      examination. It can also be used to facilitate case conference sessions and has
      potential for being used in medical education.

PMID- 8562249
TI  - Use of the reversed button device to treat an atrial septal aneurysm associated
      with a patent foramen ovale.
AB  - An atrial septal aneurysm may be associated with a patent foramen ovale. When
      paradoxical emboli result, the shunt must be closed and the atrial septal
      aneurysm excised. A reversed buttoned occluder device was successfully used for
      the transcatheter treatment of this condition.

PMID- 8562250
TI  - The paintings of pathological anatomy by Sir Robert Carswell (1793-1857).

PMID- 8562251
TI  - Guidelines for specialist training in cardiology.

PMID- 8562252
TI  - Training in cardiology: the future.

PMID- 8562253
TI  - Warm blood cardioplegia.

PMID- 8562254
TI  - ACE inhibitors after myocardial infarction: patient selection or treatment for
      all?

PMID- 8562255
TI  - Effects of streptokinase in patients presenting within 6 hours of prolonged chest
      pain with ST segment depression.

PMID- 8562256
TI  - [The intervention trial in the evaluation of antihypertensive therapy].
AB  - Several epidemiological studies carried out over the past 30 years have
      unequivocally shown that hypertension is a major risk factor for cardiovascular
      diseases, the incidence of cerebral, coronary, and peripheral artery disease
      being progressively higher as blood pressure values become more and more
      elevated. Interventional clinical trials have also shown that antihypertensive
      treatment is able, by decreasing high blood pressure values, to reduce the
      cardiovascular risk profile of the hypertensive patient, although not to
      normalize it. Furthermore, antihypertensive treatment has been demonstrated to be
      more effective in protecting against stroke and congestive heart failure than
      against coronary artery disease. This paper will review the results of the
      various interventional trials carried out in hypertensive states of different
      clinical severity and in isolated systolic hypertension of the elderly. It will
      also briefly discuss the peculiar features of the ongoing interventional clinical
      trials, whose results will allow clarification of important and still unsolved
      issues concerning antihypertensive therapy.

PMID- 8562257
TI  - [The role of the sympathetic nervous system in essential arterial hypertension
      and organ damage].
AB  - Experimental evidence collected in animals and man supports the concept that
      adrenergic neural factors may be involved in the development of the hypertensive
      state and hypertension-related cardiovascular and metabolic complications. The
      various methodological approaches employed in evaluating sympathetic tone in man
      have shown that a hyperadrenergic state is evident in the early hypertensive
      phases. Sympathetic activation becomes more evident in stable hypertension and
      contributes to the maintenance of high blood pressure values. Adrenergic factors
      are also involved in the pathogenesis of cardiac and vascular hypertrophy, i.e.
      cardiovascular hypertensive complications that in the past have been regarded as
      mainly dependent on hemodynamic mechanisms. Sympathetic overactivity may also
      play an important role in the atherogenic process and may contribute to the
      insulin resistance state that often characterizes the hypertensive patient. The
      role of neural sympathetic factors in the pathophysiology of hypertension and its
      complications suggests that modulation of sympathetic activity should be an
      important target of modern antihypertensive treatment, aimed not only at lowering
      blood pressure, but also at reducing the patient's cardiovascular risk profile.

PMID- 8562258
TI  - [Hypertension and diabetes].
AB  - The prevalence of hypertension in diabetes is significantly higher than in non
      diabetics, perhaps twice as common. The excess is related to diabetic
      nephropathy, mainly in type 1 diabetes, to obesity, mainly in type 2 diabetes,
      but also to increased sympathetic activity. Furthermore, the increased prevalence
      of hypertension may relate to insulin resistance and its sequelae. Insulin
      resistance leads to hyperinsulinemia, relates to increased LDL and reduced HDL
      levels, causes the development of impaired glucose tolerance and type 2 diabetes
      and might also be causally related to the onset of hypertension. Syndrome X has
      relevant therapeutic implications in the management of hypertension. Hypertension
      is a major risk factor for large vessel disease in diabetics and also a risk
      factor for microangiopathy, particularly nephropathy. The incidence of
      atherosclerotic disease is dramatically increased in both type 1 and type 2
      diabetics and is the major cause of morbidity and premature death mainly in
      patients with raised urinary albumin excretion. Thus, diabetics show a two-fold
      increased risk of coronary heart disease, 2-6 fold increased risk of stroke and a
      several-fold increased risk of peripheral vessel disease. Some evidence suggests
      that hypertension may be a risk factor for retinopathy, particularly its
      progression, but surely hypertension is a significant risk factor for
      nephropathy, accelerating its progression and perhaps even causing the onset of
      the glomerulopathy. The mechanisms by which hypertension might contribute to the
      evolution of both large vessel as well as small vessel disease is still unknown,
      although increased capillary leakage and vascular endothelium alterations might
      be important factors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562259
TI  - [The treatment of hypertension in patients with a metabolic disorder].
AB  - Life expectancy has increased significantly in the last decades in many Western
      populations, due to the fall of total and cardiovascular death rates. However,
      morbidity for cardiovascular diseases has decreased to a smaller extent due to
      the still unsatisfactory improvement in the overall population risk profile. This
      is true for blood pressure control (with only 20% of hypertensive patients
      achieving normotension with antihypertensive drugs), hypercholesterolemia (with
      borderline-high serum cholesterol levels in 50% of the population), and smoking
      habits. Since hypertension, hypercholesterolemia, hyperglycemia and insulin
      resistance are frequently associated, further improvement in cardiovascular risk
      can be obtained only with a comprehensive approach to the hypertensive patients,
      including dietary and life style modifications and the use of antihypertensive
      drugs with beneficial effects on lipid and glucose metabolism. It has to be noted
      in fact that some antihypertensive drugs have divergent effects on lipid and
      glucose metabolism. Long-term diuretic administration may reduce glucose
      tolerance, increase serum glucose and cholesterol. Beta-adrenergic blockers with
      no sympathomimetic activity raise triglycerides and decrease HDL cholesterol. ACE
      inhibitors improve insulin sensitivity, while calcium entry blockers are neutral
      on both glucose and lipid metabolism. Recent reports suggest that alpha-1
      adrenoceptor blockers may reduce total and LDL cholesterol while alleviating
      insulin resistance and increasing HDL cholesterol.

PMID- 8562260
TI  - [Rational bases for the treatment of osteoporosis].
AB  - Bone tissue undergoes a continuous process of remodelling through resorption of
      damaged tissue by osteoclasts and apposition of new bone by osteoblasts, at the
      level of basic multicellular units (BMUs). The number of BMUs ultimately defines
      bone turnover and it is by itself a source of scarcely mineralized bone. In young
      healthy individuals bone resorption and bone formation are strictly coupled at
      the level of the individual BMU and thus of the entire skeleton. Bone loss in the
      elderly is due to both excess resorption over formation and increased turnover.
      The inhibitors of bone resorption diminishes the number of BMUs and this
      invariably decreases the rate of bone loss. However their effect at individual
      BMU is uncertain. Estrogen replacement therapy lessens the rate of bone loss in
      postmenopausal women but it does not seem to correct the imbalance between
      resorption and formation. In several studies bisphosphonates have been shown to
      induce a continuous positive balance, and this might indicate that these
      compounds are able to correct the basic alteration of bone metabolism leading to
      age-related bone loss.

PMID- 8562261
TI  - An overview of the results of clinical trials with alendronate, a promising
      treatment of osteoporosis in postmenopausal women.
AB  - The purpose of this overview is to provide a summary of recent data on the
      clinical safety and efficacy of alendronate sodium, an amino-bisphosphonate that
      is a potent and specific inhibitor of osteoclast mediated bone resorption, in the
      treatment of osteoporosis in postmenopausal women. Published data are available
      from two randomized, placebo-controlled, double-blind clinical trials of 2-year
      duration in over 470 patients with postmenopausal osteoporosis. The women studied
      were 4 to 5 years postmenopause, ages 42 to 76, with osteoporosis defined on the
      basis of low spine bone mineral density (BMD). Percent change in spine BMD was
      the primary endpoint; hip and total body BMD were secondary outcomes. In the Dose
      Ranging Study, alendronate 5 and 10 mg/day for 2 years significantly increased
      lumbar spine BMD by approximately 7.2%, which did not differ from patients
      receiving higher doses. Total hip BMD increased by 3.6 and 5.3%, respectively,
      with the 5 and 10 mg doses; 10 mg was significantly more effective than 5 mg.
      Placebo patients lost 1.2-1.4% BMD at these sites. Total body BMD also
      significantly increased with alendronate. In the Calcitonin Comparison Study,
      alendronate 10 and 20 mg/day for 2 years significantly increased spine and hip
      BMD; 100 IU of intranasal salmon calcitonin did not increase BMD at any site, and
      did not differ from placebo. Alendronate reduced bone turnover to a new steady
      state, as assessed by biochemical markers and was well tolerated. Preliminary
      reports indicate that alendronate progressively increases spine, hip, and total
      body bone mass for 3 years, with associated significant reductions in vertebral
      fractures, stature loss, and non-vertebral fractures.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8562262
TI  - [PLasma lipids and cardiovascular risk: lesions in the community].
AB  - We examined serum cholesterol levels and lipoprotein profiles as possible risk
      factors for the development of coronary heart disease by means of a review of
      epidemiological studies. At present a great body of literature reinforces the
      evidence of the etiologic role of total and LDL cholesterol and the magnitude of
      benefits deriving from its treatment. No convincing evidence has been put forward
      to indicate that the undoubtedly favourable effects of cholesterol lowering on
      coronary heart disease risk are offset by untoward effect on non-cardiovascular
      disease rates.

PMID- 8562264
TI  - [An update on the use of fluvastatin in primary hypercholesterolemia].

PMID- 8562263
TI  - [The pharmacology of the statins: the evidence of a direct antiatherosclerotic
      action].
AB  - With the increasing knowledge on the pathogenesis of atherosclerosis, it appears
      that the prevention of cardiovascular disease in the future will involve, besides
      risk factor correction, direct pharmacological control of processes occurring in
      the arterial wall. Among them, a pivotal role is played by smooth muscle cell
      migration and proliferation that, together with lipid deposition, are prominent
      features of atherogenesis and restenosis after angioplasty. Mevalonate and other
      intermediates (isoprenoids) of cholesterol synthesis are essential for cell
      growth, hence drugs affecting this metabolic pathway are potential
      antiatherosclerotic agents. Recently we provided evidence that fluvastatin,
      simvastatin, lovastatin, but not pravastatin, dose-dependently decrease smooth
      muscle cell migration and proliferation, independently of their
      hypocholesterolemic properties. The in vitro inhibition of cell migration and
      proliferation induced by simvastatin and fluvastatin (70-90% decrease) was
      completely prevented by the addition of mevalonate and partially (80%) by
      farnesol and geranylgeraniol, confirming the specific role of isoprenoid
      metabolites--probably through prenylated proteins--in regulating these cellular
      events. The present results provide evidence that HMG-CoA reductase inhibitors
      interfere directly with processes involved in atherogenesis--beyond their effects
      on plasma lipids--partially through local inhibition of isoprenoid biosynthesis.

PMID- 8562265
TI  - [Mixed dyslipoproteinemias: new therapeutic opportunities].
AB  - Familial combined hyperlipoproteinemia (FCHL) is a dyslipidemic syndrome
      prevalent in patients with coronary artery disease and characterized by variable
      expression of hypercholesterolemia, hypertriglyceridemia in a given family, with
      either or both present in affected individuals. Efforts to refine the phenotype
      of FCHL have led to the observation that elevated levels of apolipoprotein (apo)
      B are commonly observed in individuals with FCHL. An increased rate of hepatic
      secretion of apo B associated with very low density lipoproteins in subjects with
      FCHL has been clearly documented. The predominance of small, dense LDL, as
      determined by gradient gel electrophoresis, denoted LDL subclass phenotype B, has
      been associated with increased apo B levels. Two genetic traits have been
      implicated in FCHL. The first is the predominance of small dense LDL, which
      segregates as a mendelian trait. The second is a mendelian locus with large
      effects on apo B levels. Therapy of FCHL is based on statins and fibrates, as
      monotherapy or given in combination.

PMID- 8562266
TI  - [The treatment of hypercholesterolemia in primary and secondary prevention].
AB  - While a number of very effective dietary and pharmacological treatments are now
      available for the management of hypercholesterolemia, whether the significant and
      protracted lowering of cholesterolemia brings about a decline not only in
      vascular disease but also in overall mortality is still unclear. Meta-analysis
      studies have generally confirmed that "secondary" preventive treatment is highly
      effective in reducing total and coronary mortality (risk reduction of 3.2% vs
      only 0.1% in the case of "primary" prevention). However, more recent data
      underscore that continued pharmacological treatment, which can reduce
      cholesterolemia for a period of at least 1.5-2 years, may bring the patient back
      to a lower risk category, thus leading to a decline not only in coronary, but
      also in total mortality. In support of this conclusion are data from
      pharmacoeconomic studies from which, by taking as a reference the mean yearly
      cost of kidney dialysis, even in a low risk subject (50-year-old male without
      other vascular risk factors), the cost of life saved per year is about half the
      mean cost of dialysis. Lastly, comparative studies among different therapies
      indicate that in the majority of cases, treatment that reduces cholesterolemia
      more than 20% is not absolutely necessary, thus allowing the use of newer, lower
      cost drugs, some of which, e.g. fluvastatin, may require less intensive
      toxicologic monitoring in the clinic.

PMID- 8562267
TI  - [The epidemiology of osteoporotic fractures].
AB  - Fractures represent the most important consequence of osteoporosis, as well as
      the major determinant of the socio-economic costs of the disease. Distal forearm,
      vertebrae and proximal femur fractures are frequently associated with the
      disease. Colles' fractures generally occur in women, showing a progressive
      increase in incidence after the onset of menopause, and reaching a plateau at the
      age of 65 years. Vertebral fractures are often painless and fortuitously
      diagnosed so that there are not many epidemiological data available. However,
      incidence rates appear to increase steadily with aging in women, while
      accelerating only in later life in men. In the elderly population, spine
      deformities due to vertebral fractures can contribute to the worsening of
      concurrent diseases. Fractures of the proximal femur represent the gold standard
      for epidemiological studies on osteoporosis. Their incidence increases
      exponentially in women 70 years old and over, and in men aged 80 or older.
      Moreover, that, femoral fractures are associated with a substantial risk of
      nonself sufficiency and mortality. Osteoporosis-related costs vary greatly among
      countries, not only because of a different incidence of the disease, but also due
      to the different emphasis on prevention, hospitalization, and treatment. The
      current dramatic increase of the elderly population exhorts against the
      postponing of a global strategy for preventing and treating the disease.

PMID- 8562268
TI  - [The expressions of anxiety in the elderly. Their diagnosis and therapy].
AB  - Among the most common manifestations of anxiety in the elderly are those
      associated with neurological disorders. The etiology is often unclear, as anxiety
      and agitation may be a consequence of insight into the cognitive impairment
      rather than the direct expression of the neurological deficit. Benzodiazepines
      are the treatment of choice, particularly the 3-OH compounds that are non
      oxidised and without active metabolites. Concern about the use of benzodiazepines
      in the elderly may have been overstated. If used judiciously this class of drugs
      can prove extremely helpful in reducing day-time anxiety and night-time insomnia.
      Other medications that are commonly used to treat agitation and disruptive
      behaviour in demented elderly patients include antipsychotics, beta-blockers,
      trazodone, buspirone, anticonvulsants.

PMID- 8562269
TI  - [alpha-Glucosidase inhibitors in the therapy of diabetes mellitus].
AB  - The onset and progression of long-term complications in diabetes mellitus appear
      to be related to the degree of hyperglycemia and the overall metabolic control.
      Therefore, an important goal in the therapy of subjects with diabetes is to avoid
      wide fluctuations in blood glucose concentrations and increases in lipid levels.
      The first therapeutic maneuver to achieve glycemic control is to establish a
      correct diet containing complex carbohydrates and an adequate amount of dietary
      fibers. Dietary fibers are capable of reducing the intestinal uptake of
      carbohydrates. An additional strategy to reduce the uptake of carbohydrates
      across the intestine has recently been proposed by Puls et al. This strategy
      involves the use of inhibitors of alpha-glucosidase, an intestinal enzyme that
      participates in the breakdown of polysaccharides into disaccharides and
      monosaccharides. The inhibition of alpha-glucosidase by these agents is
      competitive and reversible and results in delayed and reduced uptake of
      carbohydrates across the intestine. This effect attenuates the post-prandial
      hyperglycemia and subsequent insulin secretory response particularly in subjects
      with hyperinsulinemia. The compound acarbose is a member of first generation
      alpha-glucosidase inhibitors. The administration of high doses of acarbose can be
      associated with side effects such as flatulence, meteorism, abdominal pain, and
      diarrhea due to the fermentation of non-absorbed carbohydrates in the intestinal
      lumen. Usually, these effects subside following a few days of therapy and/or
      reduction of the initial dose. Acarbose has been effectively used to treat type 2
      diabetic patients either as a first choice drug or in association with
      sulfonylurea agents and in type 1 diabetics in association with insulin
      therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562270
TI  - [Arterial hypertension and atherosclerosis: their epidemiology and
      physiopathology].
AB  - Several epidemiologic studies have demonstrated that hypertensive patients have
      an increased risk for the development of atherosclerosis. Although the appearance
      of atherosclerosis only in those parts of vascular system subjected to high blood
      pressure suggests that the mechanical stress is the principal factor involved in
      the development of atherosclerosis, the mechanisms underlying the linkage between
      hypertension and atherosclerosis are not yet completely understood. In fact, the
      evidence that antihypertensive treatments are not able to abolish the increased
      incidence of ischemic accidents in hypertensive patients suggests that other
      cellular and molecular mechanisms are involved in the pathogenesis of
      atherosclerosis. The pathogenesis of hypertension is a multifactorial process
      that involves the interaction of genetic and environmental factors which
      determine the abnormalities of volume regulation, the enhanced vasoconstriction
      and the remodeling of the arterial wall which is characterized by hypertrophy and
      proliferation of vascular smooth muscle cells. On the other hand, the increased
      growth response of vascular smooth muscle cells represents one of the principal
      characteristics of atherosclerosis. Thus, increased vascular smooth muscle cell
      growth is a common feature in the pathogenesis of both atherosclerosis and
      hypertension.

PMID- 8562271
TI  - [The pharmacological rationale for the development of a calcium antagonist in the
      prevention of damage to the arterial wall].

PMID- 8562272
TI  - [The preliminary clinical evidence from the ELSA study. The European Lacidipine
      Study on Atherosclerosis].
AB  - Up to the present the relationship between arterial hypertension or its treatment
      and cardiovascular complications has been evaluated in terms of the incidence of
      events, such as fatal and nonfatal myocardial infarction or stroke and cardiac
      deaths. However, cardiovascular events are not the direct consequence of blood
      pressure elevation, which, on the contrary, is responsible for atherosclerotic
      disease. Quantitative ultrasonography is a sensitive, specific and reproducible
      technique which, in comparison to arteriography, is non invasive and less
      expensive. The availability of this technique has allowed us to do some studies,
      one just published, another in the elaboration phase and others ongoing, aimed at
      evaluating the effects of antihypertensive agents on carotid changes in
      hypertensive patients. The European Lacidipine Study on Atherosclerosis (ELSA)
      compares the effects of lacidipine, a calcium-antagonist and of atenolol, a beta
      blocker, on blood pressure, on carotid vessel modifications, and on the incidence
      of cardiovascular events in patients with mild to moderate hypertension with a 4
      year follow-up period. Preliminary results of the study, which were concerned
      with the demographic characteristics of the first 1000 randomized patients
      enrolled, indicate that 84% of the patients had a carotid plaque, 15% had
      thickening of the intima-media, and 1% had a normal vessel. These results are
      both surprising and significant in that they admonish the physician not to
      neglect patients with mild to moderate hypertension even when they have neither
      complications nor other risk factors.

PMID- 8562273
TI  - [New therapeutic outlooks in the treatment of the hypertensive patient].
AB  - The results of the large randomized trials in which antihypertensive drugs have
      been compared to placebo demonstrated that antihypertensive therapy reduces
      cardiovascular and cerebrovascular mortality and morbidity. Nowadays, however, it
      is not enough to lower blood pressure; the goal of the treatment should be to
      prevent progression of the underlying atherosclerotic disease, reduce major and
      minor complications and improve survival and quality of life. Furthermore,
      primary prevention and risk reduction in hypertensives are dependent not only on
      the antihypertensive effect of the chosen agent, but also on improved detection
      and management of the other cardiovascular risk factors. The potential ability of
      antihypertensive treatment to exert an effect on global cardiovascular risk
      profile has become one of the most important considerations in the selection of
      an antihypertensive treatment. Thus, in patients at risk for coronary events it
      seems important to choose a drug or drug combination with a documented effect on
      coronary events. In addition, both prevention of cardiovascular events and
      prevention of organ damage and organ disease have to be considered essential
      goals of antihypertensive therapy. The prevention of organ damage associated with
      hypertension has also been facilitated by the development of effective
      antihypertensive drugs. These agents have been shown to have a beneficial
      influence on organ damage in hypertensive patients through an effective,
      continuous, smooth control of blood pressure and through specific effects on some
      of the functional and structural alterations induced by hypertension.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8562274
TI  - [Endothelial function and arterial hypertension].
AB  - In normotensive humans, the endothelium modulates vascular tone mainly by the
      production of nitric oxide. In human essential hypertension the basal release of
      nitric oxide is reduced and forearm vasodilation to the endothelium-dependent
      agonists acetylcholine or bradykinin is blunted. Defective basal release of
      nitric oxide seems to be secondary to blood pressure increase while impaired
      agonist-evoked endothelium-dependent vasodilation is probably a primary
      phenomenon. This latter endothelial dysfunction seems to be caused by the
      simultaneous presence of an alteration in the L-arginine-nitric oxide pathway and
      the production of constrictor prostanoids. Defective nitric oxide production is
      already detectable in normotensive offspring of hypertensive patients and young
      essential hypertensives. In contrast, vasoconstrictor prostanoid production seems
      to be associated with aging. In essential hypertensive patients, although only
      scanty data are available, chronic effective pharmacological treatment seems to
      restore impaired basal production of nitric oxide but does not improve vascular
      response to endothelial agonists.

PMID- 8562275
TI  - [The physiopathology of osteoporosis: the role of local factors].
AB  - Bone remodelling continues throughout life and depends on two processes that are
      tightly coupled: resorption of old bone by osteoclasts and subsequent new bone
      formation by osteoblasts. Evidence accumulated during the last few years has
      clearly indicated that bone marrow microenvironment plays an essential role in
      regulating bone remodelling. Indeed major advances in our understanding of the
      ontogeny of osteoclasts and osteoblasts indicate that both cell types derive from
      progenitors present in the marrow, and that systemic and local factors regulate
      their development and the coupling of their function. In particular, a network of
      cytokines and growth factors is essential for the regulation of both
      osteoclastogenesis and osteoblast formation: these factors play a pivotal role in
      the paracrine regulatory control of bone turnover under physiological conditions.
      Among this array of local factors, IL-6, IL-1, TNF, GM-CSF, cytokines with
      osteoclastogenic and bone resorptive properties, have been implicated in the
      pathophysiology of osteoporosis since their production is increased in vivo in
      humans and animals with estrogen deficiency. These findings provide emerging
      insights into the pathophysiology of osteoporosis and deserve further
      investigation.

PMID- 8562276
TI  - [The trough/peak ratio].
AB  - The trough-to-peak ratio expresses the quantitative relation between the
      antihypertensive effect of a drug or association of drugs measured at the end of
      a between-dose interval, and the maximum antihypertensive effect recorded during
      this interval. When this ratio is evaluated in responders, and a properly
      designed protocol that also takes blood pressure measurement into consideration
      is adopted, it becomes a reliable index of the duration-efficacy of
      antihypertensive therapy. For this reason, it constitutes a safety parameter
      required by the Food and Drug Administration to prevent the risk of drugs with
      shortlived action from being administered at excessive doses in the attempt to
      prolong the duration of drug action. In addition, a favorable trough-to-peak
      ratio (> 0.50 and preferably close to 1.0) is an index of homogeneous blood
      pressure control over a given between-dose interval. Pharmacological treatment
      that achieves this antihypertensive effect might be more efficient in preventing
      and/or causing regression of target organ damage and can improve patient
      compliance with antihypertensive therapy.

PMID- 8562277
TI  - [The cost/benefit of antihypertensive therapy].
AB  - The prevalence of arterial hypertension is very high in the general population,
      ranging from 10% in people between 20 and 30 years of age to more than 50% in the
      elderly. However the great majority of hypertensive subjects belong to the mild
      hypertension range and are at relatively low risk for cerebrovascular and cardiac
      events. As it is impossible at the present time to identify subjects who are
      particularly inclined to develop complications, all hypertensives are put under
      treatment in the attempt to avoid a few events in a very vast population. This
      implies that enormous health care resources have to be allocated. In the present
      article a number of economic evaluation techniques of hypertension are reviewed
      with special focus on methods combining quantity and quality of life.

PMID- 8562278
TI  - [The organ damage in arterial hypertension].
AB  - The development of hypertension is associated with the presence of cardiovascular
      structural alterations. The principal target organs of hypertensive disease are
      the heart, brain, kidney and eye. Although left ventricular hypertrophy is an
      initially useful and well tolerated adaptive mechanism because it tends to reduce
      wall stress, it may subsequently lead to impaired cardiac function and even heart
      failure. Vascular structural alterations include reduced compliance, the
      appearance of atheromatous lesions in the large arteries, and hypertrophy or
      remodelling of small artery walls, and may be involved in the onset of retinal,
      renal and brain lesions. Technological progress now enables us to evaluate
      cardiovascular structural alterations early on as well as to monitor their
      natural history and the modifications induced by antihypertensive therapy. There
      is no question as to capacity of antihypertensive therapy to reduce the incidence
      of stroke, heart failure, renal failure and severe hypertensive retinopathy.
      Although a number of drugs are able to lower blood pressure, ACE-inhibitors and
      calcium entry blockers more effectively bring about the regression of left
      ventricular hypertrophy and, probably, also the retrocession of structural
      alterations in small resistance arteries; they seem to have a beneficial effect
      on structural alterations in large arteries as well. Although the regression of
      left ventricular hypertrophy could be associated with an improved prognosis, no
      data are available yet on the prognostic significance of the presence and
      regression of vascular structural alterations.

PMID- 8562280
TI  - Thymidine incorporation is less sensitive to lack of zinc in human than in rodent
      cells.
AB  - The inhibition of thymidine incorporation by inadequate availability of zinc
      induced by adding a chelator to the culture medium was significantly less in
      human cell lines than in rodent cell lines. In contrast, zinc uptake into the
      human cells was inhibited by the chelator to a greater extent than with rodent
      cells. The possible implications of these observations for the dietary zinc
      requirements of humans and rodents are discussed.

PMID- 8562279
TI  - Estimation of the bioavailability of zinc and calcium from human, cow's, goat,
      and sheep milk by an in vitro method.
AB  - The availability of zinc and calcium from human, cow's, goat, and sheep milk is
      evaluated by an in vitro method that involves a simulated human gastrointestinal
      digestion followed by measurement of dialyzability of zinc and calcium. Zinc
      availability of milk showed the highest value for human milk (15.0%) and the
      lowest for sheep milk (1.0%), in both whole and skim milk. Calcium availability
      of the different types of milk did not differ significantly and ranged between 18
      and 23%. No significant differences in availability between whole and skim milk
      were found for both elements, except for zinc in cow's milk.

PMID- 8562281
TI  - Effects of concurrent administration of monensin and selenium on erythrocyte
      glutathione peroxidase activity and liver selenium concentration in broiler
      chickens.
AB  - Different toxic doses of selenium and monensin preparations were administered to
      broiler chickens. The two substances were given by oral route, alone or
      concurrently, for variable periods. Erythrocyte glutathione peroxidase (GSH-Px)
      activity was found to be elevated after the administration of the drugs. This
      increase was considerably higher when selenium and monensin were administered
      concurrently, indicating the occurrence of strong interaction between them.
      Administration of selenium led to a rapid increase in the liver selenium
      concentration. This increase, in turn, was enhanced by concurrent application of
      monensin. Monensin given alone did not have any significant effect on the changes
      of liver selenium concentration. Further results suggest that administration of
      monensin increases erythrocyte GSH-Px activity, even in the absence of
      supplemental selenium or during increased liver selenium concentration.

PMID- 8562282
TI  - Endocrine interaction between zinc and prolactin. An interpretative review.
AB  - Zinc plays a very important role in animal and human metabolism. Nowadays, it is
      one of the most extensively studied trace element, since its sphere of action has
      been demonstrated to be very broad. From the biochemical standpoint, it controls
      more than 300 different enzymes, many of them involved with intermediary
      metabolism, DNA and RNA synthesis, gene expression, and immunocompetence. It also
      plays a significant role in hormonal homeostasis, since it can interact with
      almost all hormones. Zn2+ is closely related to the thyroid and steroid hormones,
      insulin, parathormone, and pituitary hormones, particularly prolactin (PRL). Zn2+
      can inhibit PRL secretion within a range of physiologically and pharmacologically
      relevant concentrations. This property has raised the possibility of clinical
      applications of zinc. In this article, we review the literature on the subject in
      an attempt to provide a comprehensible general view.

PMID- 8562283
TI  - Daily dietary intake of copper, zinc, and selenium of exclusively breast-fed
      infants of middle-class women in Burundi, Africa.
AB  - Copper (Cu), zinc (Zn), and selenium (Se) in human milk of middle-class Burundian
      women during the first 10 mo of lactation have been determined. Wet acid
      digestion, using nitric and perchloric acids, and atomic absorption spectrometric
      analysis have been used. Daily intakes have been calculated and proven to
      decrease from 0.39 +/- 0.05 (colostrum) to 0.16 +/- 0.02 (mature milk), 2.3 +/-
      0.3 (colostrum), to 1.2 +/- 0.2 mg (mature milk) and 10.9 +/- 1.5 (colostrum) to
      5.3 +/- 0.8 micrograms (mature milk) for Cu, Zn, and Se, respectively. Since
      values for this African country are nonexistent, intake levels are compared with
      literature data and found to be somewhat higher than those observed in other
      poorly nourished countries. The recommended safe and adequate daily intake for
      infants of 0-6 mo of age, as proposed by the National Research Council of the
      USA, is only met for Burundian infants < 1 mo of age. The function of copper (Cu)
      and zinc (Zn) as essential trace elements has been known for quite a number of
      years (1). Also, selenium (Se) is a trace element essential for the activity of
      glutathione peroxidase (2) and type I iodothyronine 5-deiodinase (3). For all
      three elements, an adequate intake is necessary for satisfactory infant growth
      and development (4). In view of the almost total lack of relevant data on Burundi
      (Africa), we have determined Cu, Zn, and Se in human milk of middle-class
      Burundian women during the first 10 mo of lactation (5). The aim of this study is
      to assess infants' elemental intake for this country and compare this with
      literature data on trace elemental intake of exclusively breast-fed infants.

PMID- 8562284
TI  - Response of hepatic function to hepatic copper deposition in rats fed a diet
      containing copper.
AB  - Fischer rats were a fed diet supplied with copper chloride (150-600 ppm) for 60 d
      from weaning. Serum (glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic
      transaminase (GPT) activities were increased with the increase of Cu
      concentration in the diet. Biliary excretion of Cu was related to the dietary Cu
      level. Depositions of hepatic and renal Cu were also related to the dietary Cu
      level in a dose-dependent manner. In particular, hepatic (155.2 +/- 13.3
      micrograms/g) and renal (44.9 +/- 4.4 micrograms/g) Cu concentrations increased
      abruptly in the Cu-600 ppm group. In the liver, about 60% of Cu was distributed
      in the soluble fraction (100,000 g supernatant). In the Cu-600 ppm group, 25% of
      cystosolic Cu was bound to metallothionein (MT). Our results suggest that chronic
      exposure to Cu appears to have a deleterious effect on the hepatic function, and
      further, that even in rats with normal biliary Cu excretion, clearance of Cu from
      the liver may be marginal when dietary Cu is near the 600-ppm level. Although Cu
      is an essential nutrient, an overload of Cu should be avoided.

PMID- 8562285
TI  - Increased resistance against cadmium toxicity by means of pretreatment with low
      cadmium/zinc concentrations in Bufo arenarum embryos.
AB  - A significantly increased resistance against cadmium toxicity in Bufo arenarum
      embryos was obtained by means of pretreatments with low cadmium/zinc
      concentrations, allowing embryos to tolerate lethal cadmium concentrations.
      Slight variations in the pretreatment schedule could result in significant
      differences within this acclimation phenomenon. The probable mechanisms of action
      of this protective effect are discussed.

PMID- 8562286
TI  - Study of distribution and interaction of arsenic and selenium in rat thyroid.
AB  - Seventy-eight Wistar weanling rats were pretreated with arsenate (100 mg/L As),
      selenite (1 mg/L Se), and arsenate (100 mg/L As) plus selenite (1 mg/L Se) added
      to the drinking water. After 4 w, all the animals were sacrificed and serum T3
      and T4 were determined by double-antibody radioimmunoassay. Thyroid tissue
      concentrations of As and Se were determined in female rats by neutron activation
      analysis, and tissue specimens were examined histopathologically. For both sexes,
      the measurements indicated that T4/T3 was lowest in the Se group, intermediate in
      the As group, and highest in the controls. Corrected for the mean value of the
      controls, mean As concentration of thyroid tissue was of the same magnitude in
      the group pretreated with As + Se as the sum of the mean As concentration in the
      groups pretreated with As or Se alone. The outcome was symmetric with regard to
      the Se concentration: In the As + Se pretreated group, the mean Se concentration
      was of the same magnitude as the sum of the mean Se concentration in the groups
      pretreated with As or Se alone. Thus, As and Se tended to accumulate in the
      thyroid tissue. Postmortem examination showed that the thyroid tissue of rats
      pretreated with As alone exhibited obvious, toxic changes, whereas only minor or
      no changes were found in the tissues of the groups pretreated with Se or As + Se,
      and in the tissues of the controls. Multivariate analyses demonstrated that s-T4
      and s-T3 were significantly correlated with sex, that s-T3 was positively
      correlated (p < or = 0.001) with Se pretreatment, and that the T4/T3 ratio was
      negatively correlated with both As (p < or = 0.012) and Se pretreatment (p < or =
      0.001). The results were discussed in relation to the cancer preventive effect of
      Se.

PMID- 8562287
TI  - Storage and preservation of blood and urine for trace element analysis. A review.
AB  - In any well-defined study, a sample preservation and storage scheme compatible
      with the information or analyte sought should be incorporated. This article
      emphasizes the need for preservation and storage of biological fluids collected
      for trace element determination; cites the major factors, such as container
      material, container pretreatment, storage time, storage temperature, and
      contamination of the laboratory environment affecting preservation; presents a
      historical account of the available literature studies on the preservation and
      storage of trace metals in whole blood, plasma, serum, and urine; and makes
      recommendations on the most effective storage and preservation methods.

PMID- 8562288
TI  - Clinical and laboratory assessment of zinc deficiency in Dutch children. A
      review.
AB  - The clinical spectrum of acrodermatitis enteropathica (n = 226) is compared with
      symptoms reported in other Zn deficiencies: total parenteral nutrition without Zn
      (n = 21), protein energy malnutrition (n = 24), gastrointestinal disease (n =
      79), geophagia (n = 227), and dietary low intake (n = 23). Common features of
      deficiency are diarrhea, recurrent infection, and growth retardation. Dermatitis
      is less common in other types of deficiency than in acrodermatitis enteropathica
      (9 vs 88% of cases). Anorexia and/or hypogeusia is reported more frequently in
      the other types of deficiency (30 vs 16%). The main symptoms in acrodermatitis
      enteropathica vary with age. These differences in the clinical picture of Zn
      deficiency are discussed in relation to the degree of the deficiency (acute,
      subacute, or chronic; severe, mild, or subclinical). The results of the
      conventional laboratory tests to diagnose Zn deficiency (Zn levels in serum,
      urine, or hair) are reviewed. In healthy Dutch infants and children, the mean
      values of these levels vary by a factor of 1.6-3.0. Also, the clinical
      interpretation of their results is prone to errors. Therefore, we advocate the
      erythrocytic 65Zn uptake test. Its mean varies by 1.3. However, its reference
      values for different age intervals need to be established. From the comparison of
      the results of three conventional tests of samples taken concurrently (serum,
      urine, and hair) in groups of Dutch children with symptoms common in Zn
      deficiency (diarrhea, recurrent infection, or growth retardation), it is
      estimated that +/- 1% of Dutch children with minor complaints suffer from either
      acute or subacute Zn deficiency. Other deficiencies occur occasionally. In order
      to detect the individual patient with deficiency, the erythrocytic 65Zn uptake
      test is promising and needs to be evaluated. Therefore, we review a set of
      reference laboratory tests with results that alter during sequential stages of
      overload and deficiency. Such a scheme is advocated as a guidance for future
      clinical research on deficiency, and solves the problem of differentiating those
      conditions that identify the individual patients who need treatment by
      supplementation.

PMID- 8562289
TI  - Selenium and cellular immunity. Evidence that selenoproteins may be encoded in
      the +1 reading frame overlapping the human CD4, CD8, and HLA-DR genes.
AB  - Selenium deficiency can lead to impaired immune function and reduced T-cell
      counts, as well as various specific disorders. Significantly, in ARC and AIDS
      patients, a progressive decline in plasma Se, paralleling T-cell loss, has been
      widely documented. Since evidence now suggests that there is an extremely high
      turnover of CD4+ T-cells in AIDS patients, with billions of new cells lost and
      replaced daily, any exceptional requirement for Se in lymphocytes could
      contribute to this progressive Se depletion. Thus, it may be significant that,
      overlapping the known genes in the +1 reading frame, the mRNAs of several T-cell
      associated genes (CD4, CD8, HLA-DR p33) have open reading frames (ORFs) with as
      many as 10 in-frame UGA codons (CD4, p33), a clustering that is highly improbable
      by chance alone, and reminiscent of selenoprotein P, the predominant plasma form
      of Se. The presence of these ORFs, along with potential stem-loop RNA structures
      displaying consensus selenocysteine insertion sequences, AUG(N)mAAA(N)nUGR,
      suggests that these mRNAs may encode selenoproteins, in addition to the known T
      cell glycoproteins. If so, the roles of Se in the immune system may be more
      diverse than previously suspected.

PMID- 8562290
TI  - Zinc, copper, and zinc- or copper-dependent enzymes in human hypertension.
AB  - Imbalance of zinc and copper status has been hypothesized in human hypertension.
      A case-control study was carried out to elucidate the possible relationship
      between zinc and copper status and essential hypertension. Thirty-one subjects
      affected by mild stable hypertension, pharmacologically untreated, were
      investigated together with 31 normotensive controls individually matched for sex,
      age, and smoking habits. Zinc and copper in serum and urine wee measured, and
      serum activities of alkaline phosphatase (AP), lactic dehydrogenase (LDH), copper
      zinc superoxide dismutase (Cu-Zn SOD), lysyl oxidase (LOX), and monoamine oxidase
      (MAO) were evaluated. No significant difference in serum and urine zinc and
      copper content as far as in serum activity of zinc (AP and LDH) or copper (Cu-Zn
      SOD, LOX, and MAO)-dependent enzymes was found between hypertensives and
      normotensives. Positive relationships were found in normotensives between serum
      and urine levels of zinc (r = 0.577; p = 0.001) and copper (r = 0.394; p =
      0.028), and between serum copper and Cu-Zn SOD (r = 0.534; p = 0.002). In
      normotensives, diastolic blood pressure and serum zinc were positively related (r
      = 0.370; p = 0.041). In hypertensives, inverse correlations were observed between
      diastolic blood pressure and AP (r = -0.498; p = 0.004) and Cu-Zn SOD (r = 0.452;
      p = 0.011), and between systolic blood pressure and LOX (r = -0.385; p = 0.033).
      Diastolic blood pressure was related to LDH inversely in hypertensives (r = 
      0.357; p = 0.049) and positively in normotensives (r = 0.457; p = 0.010). In
      normotensives, diastolic blood pressure was inversely related with MAO (r = 
      0.360; p = 0.046). These findings support the hypothesis that an imbalance of
      zinc and copper status might be involved in human hypertension.

PMID- 8562291
TI  - Zidovudine therapy in HIV infection: which patients should be treated and when.

PMID- 8562292
TI  - Effects of peripherally and centrally acting analgesics on somato-sensory evoked
      potentials.
AB  - 1. The effects of aspirin 1000 mg, paracetamol 1000 mg, codeine 60 mg on
      somatosensory evoked potentials (SEPs) were measured in a four-way cross-over
      study. 2. SEPs were elicited by electrical stimulation of the skin overlying the
      digital nerve at intensities close to pain threshold. 3. Amplitudes and latencies
      of both early and late SEPs were recorded, as well as first sensory threshold and
      subjective pain threshold. 4. None of the study medications affected the
      amplitude or latency of the late SEP components (100-250 ms post-stimulus). The
      amplitude of early components (15-30 ms post-stimulus) was also unaffected, but
      aspirin shortened the latency 30 min after ingestion. 5. Sensory detection and
      pain threshold to electrical skin stimulation were also unaffected by any of the
      study medications despite subjective central effects with codeine.

PMID- 8562293
TI  - The psychomotor and cognitive effects of litoxetine in young and middle aged
      volunteers.
AB  - 1. The effects of a range of doses of litoxetine (twice daily for 4 days), a
      novel specific serotonin re-uptake inhibitor, were evaluated in young and middle
      aged volunteers. 2. Psychometric testing was carried out at various time points
      on days 1 and 4 of each treatment period. The test battery consisted of critical
      flicker fusion (CFF), choice reaction time (CRT), compensatory tracking (CTT),
      Stroop and Sternberg memory scanning tests. Subjective feelings of sleep and
      sedation were measured by the Leeds Sleep Evaluation Questionnaire (LSEQ) and
      line analogue rating scales (LARS). 3. Pharmacokinetic profiles were determined
      from analyses of blood samples taken after the final dose on day 5. 4. Overall,
      there were few changes in any of the psychometric tests and although the higher
      doses of litoxetine improved CFF, these effects were weak in that differences
      could only be detected when the results were pooled against time. 5. The
      pharmacokinetic profile of litoxetine was very similar in both the young and
      middle aged subjects, and there was no difference regarding tolerability. 6.
      There is little evidence from this study to suggest that litoxetine has any
      intrinsic sedative activity which is likely to interfere with the performance of
      activities of everyday life.

PMID- 8562294
TI  - Enantioselective disposition of hydroxychloroquine after a single oral dose of
      the racemate to healthy subjects.
AB  - 1. Stereoselectivity in the disposition of hydroxychloroquine was investigated in
      23 healthy males following a single oral dose of 200 mg racemic HCQ (rac-HCQ)
      sulphate. Total concentrations (R+S) and R/S ratios of HCQ and its metabolites
      were measured by stereoselective h.p.l.c. 2. HCQ was detected in whole blood and
      urine, up to 91 and 85 days after dosing, respectively. Metabolites could not be
      detected in whole blood while in urine detectable concentrations were still
      present after 85 days. The blood concentrations of HCQ enantiomers were
      measurable until 168 h post-dose. 3. R(-)-HCQ accounted for 62 +/- 3% (mean +/-
      s.d.) of the AUC of rac-HCQ AUC. The elimination half-life of S(+)-HCQ (457 +/-
      122 h) was significantly shorter than that of R(-)-HCQ (526 +/- 140 h), partly
      due to its faster urinary excretion and hepatic metabolism. Its renal clearance
      was twice that of R(-)-HCQ (4.61 +/- 4.01 vs 1.79 +/- 1.30 1 h-1), and
      metabolites derived from the S-isomer represented 80-90% of the urinary recovery
      of the dose. 4. Over 85 days, 4.4 +/- 2.9 and 3.3 +/- 1.8% of the dose was
      recovered in urine as unchanged S(+)-HCQ and R(-)-HCQ, respectively. For the
      first 2 weeks, S(+)-HCQ excretion rate clearly surpassed that of R(-)-HCQ whereas
      afterwards the inverse was observed. However, since the first 2 weeks account for
      95% of rac-HCQ renal excretion, the total urinary excretion of S(+)-HCQ clearly
      surpassed that of R(-)-HCQ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562295
TI  - Grapefruit juice-felodipine interaction: reproducibility and characterization
      with the extended release drug formulation.
AB  - 1. Felodipine 10 mg extended release was administered with 250 ml regular
      strength grapefruit juice or water in a randomized crossover manner followed by a
      second grapefruit juice treatment in 12 healthy men. The pharmacokinetics of
      felodipine and primary oxidative metabolite, dehydrofelodipine, were evaluated.
      2. Initial grapefruit juice treatment increased felodipine AUC (mean +/- s.d.;
      56.6 +/- 21.9 vs 28.1 +/- 11.5 ng ml-1 h; P < 0.001) and Cmax (8.1 +/- 2.5 vs 3.3
      +/- 1.2 ng ml-1; P < 0.001) compared with water. Felodipine tmax (median; 2.8 vs
      3.0 h) and t1/2 (7.3 +/- 3.7 vs 6.9 +/- 3.6 h) were not altered. 3.
      Readministration of felodipine with grapefruit juice produced mean felodipine AUC
      (61.5 +/- 32.2 ng ml-1 h) and Cmax (8.4 +/- 4.8 ng ml-1) which were similar to
      the initial grapefruit juice treatment 1-3 weeks previously. Felodipine AUC (r =
      0.73, P < 0.01) and Cmax (r = 0.69, P < 0.02) correlated between grapefruit juice
      treatments among individuals. 4. The % increase in felodipine AUC with the
      initial grapefruit juice treatment compared with water correlated with the %
      increase in felodipine Cmax among individuals (r = 0.80, P < 0.01).
      Dehydrofelodipine AUC (74.7 +/- 28.7 vs 48.5 +/- 16.3 ng ml-1 h; P < 0.01) and
      Cmax (12.1 +/- 2.9 vs 7.9 +/- 2.6 ng ml-1; P < 0.01) were augmented with
      grapefruit juice compared with water.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562296
TI  - High prevalence of persistent cough with angiotensin converting enzyme inhibitors
      in Chinese.
AB  - 1. Angiotensin converting enzyme (ACE) inhibitors are in common use for the
      treatment of hypertension and heart failure. Whereas they are, in general, well
      tolerated, a dry cough can develop which, on occasion, requires termination of
      therapy. The reported prevalence of cough with ACE inhibitor therapy has varied
      from 0.2 to 25%, depending upon methods of data collection, analysis and symptom
      reporting. 2. To evaluate the prevalence of cough in Chinese patients receiving
      ACE inhibitors, interviews were carried out in 191 patients in Hong Kong who were
      taking therapy which included captopril or enalapril for hypertension or heart
      failure, and 382 patients matched for sex and age receiving alternative
      medications which excluded an ACE inhibitor (controls). Patients and controls
      were interviewed in a blinded manner by the same interviewer using a common
      adverse-effect questionnaire. 3. Persistent cough was reported in 44% of patients
      taking an ACE inhibitor (46% of those receiving captopril and 41.8% of patients
      taking enalapril), and in 11.1% of the controls (P < 0.001). The prevalence of
      other adverse reactions was similar, with no significant difference between the
      two treatment groups. The complication of cough was not related significantly to
      age, sex, underlying disease, drug dosage or smoking status. 4. This study
      indicates that cough is a common side effect of treatment with ACE inhibitors in
      Hong Kong Chinese, although in most patients cessation of therapy is not
      required. Whether Chinese are particularly susceptible to ACE-inhibitor cough
      requires a formal prospective study comparing Chinese and non-Chinese patients.

PMID- 8562297
TI  - Respiratory depression following morphine and morphine-6-glucuronide in normal
      subjects.
AB  - 1. Morphine 6-glucuronide (M6G) is a metabolite of morphine with analgesic
      activity. A double-blind, randomised comparison of the effects of morphine and
      M6G on respiratory function was carried out in 10 normal subjects after i.v.
      morphine (10 mg 70 kg-1) or M6G (1, 3.3 and 5 mg 70 kg-1). Analgesic potency was
      also assessed using an ischaemic pain test and other toxic effects were
      monitored. 2. Following morphine there was a significant increase in arterial
      PCO2, as measured by blood gases 45 min post dose (0.54 +/- 0.24 (s.d.) kPa, P <
      0.001), and in transcutaneous PCO2 from 15 min post dose until the end of the
      study period (4 h), whereas blood gas and transcutaneous PCO2 were unchanged
      after M6G at 1.0, 3.3 and 5.0 mg 70 kg-1. This increased PCO2 following morphine
      was associated with an increase in expired CO2 concentration (FECO2) (0.20 +/-
      0.14% expired air at 15 min post dose, P = 0.002), compared with small but
      significant reductions in FECO2 following morphine 6-glucuronide (-0.15 +/- 0.17%
      at 1 mg 70 kg-1 P = 0.030, -0.14 +/- 0.15% at 3.3 mg 70 kg-1 P = 0.017, -0.18 +/-
      0.11% at 5 mg 70 kg-1 P = 0.024). Maximum transcutaneous PCO2 was significantly
      increased after morphine (0.63 +/- 0.28 kPa P = 0.009), but was not changed after
      M6G at 1 mg (0.10 +/- 0.34 kPa P = 0.11) 3.3 mg (0.06 +/- 0.37 kPa P = 0.34) or 5
      mg (0.26 +/- 0.07 kPa P = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562298
TI  - Lack of effect of gender and oral contraceptive steroids on the pharmacokinetics
      of (R)-ibuprofen in humans.
AB  - The effects of gender and oral contraceptive steroids on the pharmacokinetics of
      (R)-ibuprofen were studied in groups of healthy adult males, females and oral
      contraceptive steroid (OCS) using females. The values of AUC, CLpo, t1/2 and Vss,
      app did not differ significantly between the groups. Similarly, the percentage
      unbound of (R)-ibuprofen in pooled plasma from the three groups was not
      statistically different. Since chiral inversion is the major determinant of (R)
      ibuprofen clearance in humans, it may be inferred from these data that gender and
      OCS have little or no effect on conversion of (R)-ibuprofen to the
      pharmacologically active S-enantiomer. Moreover, it is unlikely that hormonal
      factors influence the activity of the human hepatic long-chain fatty-acid:CoA
      ligase, the enzyme mediating the rate limiting step of (R)-ibuprofen inversion.

PMID- 8562299
TI  - Pharmacokinetic interaction studies between felbamate and vigabatrin.
AB  - To assess the possible occurrence of pharmacokinetic interactions between the
      antiepileptic agents felbamate and vigabatrin, two randomized, double-blind,
      placebo-controlled, crossover studies were conducted in healthy male volunteers.
      In Study I, 18 subjects received oral vigabatrin 1000 mg every 12 h for two 8
      days periods with felbamate 1200 mg every 12 h or placebo. In Study II, 18 other
      volunteers were administered oral felbamate 1200 mg every 12 h for two 8 days
      periods with vigabatrin 1000 mg every 12 h or placebo. On the eighth day of each
      treatment period, blood and urine samples were collected over 12 h for
      determination of the active S(+)- and inactive R(-)-vigabatrin enantiomer
      concentrations (Study I) or felbamate concentrations (Study II). In Study I, the
      pharmacokinetic parameters of R(-)-vigabatrin were similar during co
      administration with felbamate or placebo. Felbamate produced a 13% increase in
      AUC(0.12 h) and an 8% increase in urinary excretion of S(+)-vigabatrin. Although
      these changes were statistically significant, their magnitude was small. In Study
      II, the pharmacokinetic parameters of felbamate were similar during concurrent
      administration with vigabatrin or placebo. These data indicate that there are no
      clinically relevant pharmacokinetic interactions between felbamate and vigabatrin
      in man.

PMID- 8562300
TI  - Lack of interaction between nefazodone and cimetidine: a steady state
      pharmacokinetic study in humans.
AB  - The steady-state pharmacokinetic interaction between nefazodone and cimetidine
      was evaluated in a three-period crossover study consisting of three treatments of
      1 week duration with a 1 week washout between treatments. The 18 healthy, male
      study subjects received: nefazodone hydrochloride 200 mg twice daily (every 12 h)
      for 6 days; cimetidine 300 mg four times daily for 6 days; and 200 mg nefazodone
      hydrochloride twice daily + 300 mg cimetidine four times daily for 6 days. On day
      7 of each treatment, only the morning dose was administered. Serial blood samples
      were collected for pharmacokinetic analysis after drug administration on day 7 of
      each treatment; blood samples for trough levels (Cmin) to assess attainment of
      steady state, were also collected just prior to the morning doses on days 2-7 of
      each study period. Plasma samples were assayed for cimetidine, and nefazodone and
      its metabolites hydroxynefazodone and m-chlorophenylpiperazine by specific,
      validated h.p.l.c. methods. Statistical analyses of Cmin data indicated that,
      regardless of treatment, steady state was achieved for cimetidine by day 2 and
      for nefazodone and its metabolites by day 3 of multiple dosing, and that there
      were no significant differences in Cmin levels between treatments. When
      nefazodone and cimetidine were co-administered for 1 week, no change in steady
      state pharmacokinetic parameters for cimetidine, nefazodone or hydroxynefazodone
      was observed compared with each drug dosed alone.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8562301
TI  - Evidence for the polymorphic oxidation of debrisoquine and proguanil in a Khmer
      (Cambodian) population.
AB  - The frequency distributions of the urinary metabolic ratios of debrisoquine and
      proguanil were measured in a population of unrelated Khmers. Out of 98 Khmer
      subjects studied, two were identified as poor metabolisers of debrisoquine when a
      metabolic ratio of 12.6 was used as the cut off point. This represents a
      prevalence of debrisoquine poor metabolisers of 2.1% (95% confidence interval
      0.25-7.3%) which is similar to other Asian populations. Based on the distribution
      of the ratio of proguanil to cycloguanil excreted in urine, and using an antimode
      value of 10, the prevalence of poor metabolisers of proguanil in a Khmer
      population was estimated to be 18.4% (95% confidence interval 10.9-28.1%). The
      frequency of poor metabolisers of proguanil in Khmers was higher than that
      described for Caucasian populations, but similar to most reported results in
      Asian populations.

PMID- 8562302
TI  - Effect of diadenosine phosphates on human umbilical vessels: novel platelet
      derived vasoconstrictors.
AB  - The responses of human isolated umbilical artery to the novel platelet-derived
      mediators, diadenosine phosphates, P1,P5-di(adenosine-5')pentaphosphate (AP5A)
      and P1,P6-di(adenosine-5')hexaphosphate (AP6A) were studied in vitro. AP5A (1 nM
      300 microM; n = 7) and AP6A (1 nM-30 microM; n = 5) produced transient
      concentration-dependent contractions. Responses to AP5A were unaffected by co
      incubation with indomethacin (10 microM; n = 4), NGmonomethyl-L-arginine (L-NMMA;
      300 microM; n = 4) and theophylline (1 microM; n = 5). These results demonstrate
      that diadenosine phosphates have constrictor effects on human blood vessels in
      vitro and are consistent with a role for these platelet-derived mediators in the
      regulation of blood vessel tone.

PMID- 8562303
TI  - The spontaneous reporting of adverse drug reactions by nurses.
AB  - In an attempt to improve the low reporting rate of adverse drug reactions (ADR)
      we examined the potential for hospital nurses to report ADRs through a
      spontaneous 'yellow card' system. Over 14 months 100 cards were received
      (compared with 28 cards from doctors). Although reports from doctors for the same
      period were of a more substantial nature, nurses nevertheless reported many life
      threatening (17%) or moderately severe (76%) reactions. Nurses identified
      uncertainty concerning their role and deficient in-service education on drug
      therapy as major constraints in their participation. Given their unique position
      in drug administration and recording observations on patients, we believe that
      nurses could contribute significantly and in a complementary fashion to the
      spontaneous reporting of adverse reactions.

PMID- 8562304
TI  - Regulation of multidrug resistance through the cAMP and EGF signalling pathways.
AB  - The development of cross-resistance to many natural product anticancer drugs,
      termed multidrug resistance (MDR), is a serious limitation to cancer
      chemotherapy. MDR is often associated with overexpression of the MDR1 gene
      product, P-glycoprotein, a multifunctional drug transporter. Understanding the
      mechanisms that regulate the transcriptional activation of MDR1 may afford a
      means of reducing or eliminating MDR. We have found that MDR1 expression can be
      modulated by type I cAMP-dependent protein kinase (PKA). This suggests that MDR
      may be modulated by selectively downregulating PKA activity to effect inhibition
      of PKA-dependent trans-activating factors which may be involved in MDR1
      transcription. High levels of type I PKA occur in primary breast carcinomas and
      patients exhibiting this phenotype show decreased survival. The selective type I
      PKA inhibitors, 8-Cl-cAMP and Rp8-Cl-cAMP[S], may be particularly useful for
      downregulating PKA, and inhibit transient expression of a reporter gene under the
      control of MDR1 promoter elements. Thus, investigations of the signalling
      pathways involved in transcriptional regulation of MDR1 may lead to a greater
      understanding of the mechanisms governing the expression of MDR and provide a
      focus for pharmacological intervention.

PMID- 8562305
TI  - Type III cGMP-inhibited cyclic nucleotide phosphodiesterases (PDE3 gene family).
AB  - Seven different but related cyclic nucleotide phosphodiesterase (PDE) gene
      families have been identified. Type III cGMP-inhibited (cGI) PDEs, the PDE3 gene
      family, are found in many tissues. cGI PDEs exhibit a high affinity for both cAMP
      and cGMP, and are selectively and relatively specifically inhibited by certain
      agents which augment myocardial contractility, promote smooth muscle relaxation
      and inhibit platelet aggregation. Adipocyte, platelet, and hepatocyte cGI PDE
      activities are regulated by cAMP-dependent phosphorylation. Insulin-induced
      phosphorylation/activation of adipocyte and hepatocyte cGI PDEs is thought to be
      important in acute regulation of triglyceride and glycogen metabolism by insulin.
      Two distinct cGI PDE subfamilies, products of distinct but related genes, have
      been identified. They exhibit the domain structure common to PDEs with a
      carboxyterminal region, conserved catalytic domain and divergent regulatory
      domain. In their catalytic domains cGI PDEs contain a 44 amino acid insertion not
      found in other PDE families. The expression of cGIP1 and cGIP2 mRNAs differs in
      different rat tissues, suggesting distinct functions for the two cGI PDE
      subfamilies, i.e., cGIP1 in adipose tissue, liver, testis and cGIP2 in
      myocardium, platelets and smooth muscle.

PMID- 8562306
TI  - The heat-stable protein kinase C (PKC) stimulatory factor in the rat ovary may
      allow PKC to be active independent of cell membrane lipids.
AB  - A protein kinase C (PKC) stimulatory factor in heat-treated ovarian cytosol
      appears to be protein in nature as it was susceptible to proteinase K digestion
      and strong acid, and its lipid-substituting properties were retained after
      extraction of lipids. Phosphorylation of substrate by PKC stimulated by the
      factor from heat-treated ovarian cytosol in the absence of lipids was subject to
      dephosphorylation by the ovarian phosphatase. The factor stimulated purified PKC
      obtained from a commercial source as well as PKC partially purified from rat
      brain. Heat-treated ovarian cytosol stimulated PKC phosphorylation of myelin
      basic protein, but not protamine sulphate, in a calcium-dependent manner.

PMID- 8562307
TI  - Monoclonal antibody binding to a receptor on nonspecific cytotoxic cells (NCC)
      increases the expression of proto-oncogene kinases and protein kinase C.
AB  - Teleost nonspecific cytotoxic cells (NCC) initiate various cell triggering
      responses following receptor-target cell interactions. A putative receptor
      protein on NCC may alternatively initiate signalling processes following
      crosslinkage by homologous anti-receptor mab 5C6. In the present study, we
      demonstrated that binding to this receptor by mab 5C6 produced increased levels
      of expression of cytoplasmic src family proto-oncogene kinases lck, fyn and src.
      The phosphorylated isoforms of each kinase were approximately the same molecular
      weight (p60). Unlike their mammalian T-cell and natural killer (NK) cell
      counterparts, NCC p56lck did not autophosphorylate on tyrosine residues. This was
      determined by a lack of Western blot reactivity of teleost p56lck with anti
      phosphotyrosine specific antibodies PT-66 or 4G10. Additional evidence for this
      lack of tyrosine phosphorylation was shown by experiments treating mab 5C6
      activated NCC with sodium orthovanadate. This protein tyrosine phosphatase
      inhibitor did not affect levels of p56lck autophosphorylation. Mab 5C6 activated
      NCC were also examined to determine if levels of protein kinase C (PKC)
      expression were affected during triggering responses. Maximum increased PKC
      levels occurred 5-10 min following binding. The NCC receptor-activated PKC
      consisted of a 60,000 M(r) isoform and a 30,000 M(r) homologue equivalent to the
      mammalian PKC catalytic subunit. Not all kinases examined, however, were affected
      by mab 5C6 binding. Levels of expression of c-myc and cdc2p34 did not change
      following NCC activation. This is the first study of NK-like cells in cold
      blooded vertebrates regarding the expression of these vital intermediary
      transducing kinases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562308
TI  - Modulation of Ca2+ channels by alpha 1A- and alpha 2A-adrenoceptors in vascular
      myocytes: involvement of different transduction pathways.
AB  - Using subtype-selective agonists and antagonists, and antibodies directed against
      phosphatidylinositol and G-proteins, it has been shown in single myocytes of rat
      portal vein that both alpha 1A- and alpha 2A-adrenoceptors modulate Ca2+ channels
      through two distinct transduction pathways. alpha 1A-adrenoceptors couple with a
      Gq/G11 protein to activate a phospholipase C (PLC) which hydrolyses
      phosphatidylinositol to generate inositol 1,4,5-trisphosphate (InsP3) and
      diacylglycerol (DAG). InsP3 releases intracellular stored Ca2+ as evidenced by
      microspectrofluorimetry with Fura-2. The large and transient increase in [Ca2+]i
      activates chloride channels leading to a membrane depolarization that opens
      voltage-gated Ca2+ channels. In addition, DAG activates transiently protein
      kinase C (PKC) which increases the opening probability of Ca2+ channels through a
      phosphorylation-dependent process. alpha 2A-adrenoceptors do not induce Ca2+
      release from intracellular stores but promote sustained Ca2+ influx through
      voltage-gated Ca2+ channels. The coupling involves a Gi-protein and activation of
      PKC by DAG. These two transduction pathways may be involved in the physiological
      action of noradrenaline in vascular smooth muscles.

PMID- 8562309
TI  - Comparative analysis of chemotaxis in Dictyostelium using a radial bioassay
      method: protein tyrosine kinase activity is required for chemotaxis to folate but
      not to cAMP.
AB  - The role of signal transduction during chemotaxis of Dictyostelium discoideum
      cells to cAMP and folic acid was investigated using a radial bioassay technique.
      The effects of signalling agonists were assessed by measuring the diameters of
      visible rings formed by the outward migration of amoebae up radial gradients of
      chemoattractant. This rapid and simple bioassay method yields chemotactic rates
      equivalent to more complex assay systems. In support of previous studies,
      chemotaxis toward both cAMP and folic acid was inhibited in a dose-dependent
      manner by LaCl3, EDTA, chlorotetracycline and A1F3, supporting the importance of
      calcium ions and G protein-mediated signalling in both chemotactic events. The
      work was extended by examining the effects of the protein tyrosine kinase
      inhibitor genistein. This agent inhibited chemotaxis to folate in a dose
      dependent manner but had no observable effect on chemotaxis toward cAMP. The
      notion that phosphorylation of proteins on tyrosine residues is critical for
      chemotaxis to folic acid was supported by Western blotting experiments with
      monoclonal anti-phosphotyrosine antibodies which detected two candidate proteins
      of M(r) 52,000 and 38,000 in the membranes of folate-responsive amoebae. These
      two bands disappeared with starvation which leads to the loss of responsiveness
      of folic acid and the acquisition of responsiveness to cAMP. Time-lapse
      videomicrography also revealed some unique differences in chemotactic response.
      Starved cells responded to cAMP as individuals but feeding cells chemoattracted
      to folic acid on a populational basis. The ability to compare two different types
      of chemotaxis using a simple, rapid and accurate bioassay system should enhance
      future studies of chemotaxis in wild-type and mutant strains of D. discoideum.

PMID- 8562310
TI  - The presence of phorbol ester responsive and non-responsive forms of the zeta
      isozyme of protein kinase C in mouse epidermal cells.
AB  - The possible involvement of zeta isozyme of protein kinase C (PKC zeta) in
      phorbol ester-induced signal transduction was investigated in mouse epidermal
      cells. Western blot analysis of RESOURCE Q column chromatography eluates obtained
      from 105,000 g supernatants and particulate fractions of epidermal cells was
      performed using anti-PKC zeta specific antibody. Anti-PKC zeta antibody
      recognised proteins in low salt range corresponding to 25-125 mM NaCl (low salt
      eluted PKC zeta; 1-PKC zeta) as well as high salt range corresponding to 175-300
      mM NaCl (high salt-eluted PKC zeta; h-PKC zeta) in both subcellular fractions. 1
      PKC zeta and h-PKC zeta were detected as a doublet protein of 79,000 and 85,000
      M(r) in 105,000 g supernatants, but as a 79,000 M(r) protein in particulate
      fractions. Immunoprecipitated 1-PKC zeta and h-PKC zeta with anti-PKC zeta
      specific antibody possessed phosphatidylserine (PS)-dependent protein kinase
      activity, but neither 1-PKC zeta nor h-PKC zeta were further activated by 40 nM
      phorbol 12-myristate 13-acetate (PMA) in the presence of PS. Furthermore, 1-PKC
      zeta and h-PKC zeta can be autophosphorylated, indicating that both 1-PKC zeta
      and h-PKC zeta are PKC zeta. Treatment of intact epidermal cells with PMA or
      other PKC activators caused the apparent shift of 79,000 M(r) 1-PKC zeta to the
      85,000 M(r) from in particulate fractions. Prolonged treatment of the cells with
      PMA induced the downregulation of both forms of 1-PKC zeta in particulate
      fractions. Under the same condition, 1-PKC zeta in 105,000 g supernatants and h
      PKC zeta in both fractions did not respond to PMA. This apparent shift was
      reversible and the content ratio of 85,000 to 75,000 M(r) 1-PKC zeta was
      decreased by acid phosphatase treatment, indicating that the apparent shift
      results at least in part from phosphorylation of 79,000 M(r) 1-PKC zeta. Total
      activity of 1-PKC zeta was increased in association with the apparent shift from
      the 79,000 to 85,000 M(r) form in response to PMA treatment of intact epidermal
      cells. All of these results indicate that PKC zeta is present as multiple forms
      in mouse epidermal cells, and that especially 1-PKC zeta in particulate fractions
      play a significant role(s) in PMA-induced signal transduction in mouse epidermal
      cells.

PMID- 8562311
TI  - Role of tyrosine kinase in insulin release in an insulin secreting cell line (INS
      1).
AB  - Tyrosine kinases are involved in cell signalling of growth factors such as
      insulin and insulin-like growth factor (IGF-I) and others. Insulin and IGF-I
      receptors which possibly feedback on insulin release are established in insulin
      secreting cells. The role of tyrosine kinase in insulin secretion is
      controversial. Both the tyrosine kinase inhibitors tyrphostin 25 (TYR) and
      genistein (GEN), but not its structurally similar albeit biologically inactive
      analogue daidzein, increase insulin release at 16.7 mM glucose in INS-1 cells, an
      insulin secreting cell line. Tyrosine kinase activity is inhibited by GEN, but
      not diadzein. The inhibitory effects of either insulin or IGF-I on insulin
      release are abolished by 10(-4) M GEN but not by daidzein indicating an
      involvement of tyrosine kinase in the inhibitory effect of both insulin and IGF-I
      on insulin release. Since GEN was argued not to be specific for tyrosine kinase,
      several second messengers were investigated. cAMP is not influenced. The
      insulinotropic effect of acutely administered TPA is not influenced by GEN while
      in protein kinase C (PKC)-downregulated cells the insulinotropic effect of GEN is
      preserved: both indicate no involvement of PKC in GEN effect. Since pertussis
      toxin (PT) pretreatment has no effect on the inhibitory effects of IGF-I on
      insulin release, a PT-sensitive G-protein is not likely to be involved. The data
      indicate that tyrosine kinase is involved in the inhibitory effects of insulin
      and IGF on insulin release in INS-1 cells, possibly mediating the negative
      feedback effect.

PMID- 8562312
TI  - Determination of phosphodiesterase activity in rat mast cells using the
      fluorescent cAMP analogue anthraniloyl cAMP.
AB  - Cyclic AMP and the isozyme families that control its concentration have an
      important role in rat mast cells. We have attempted to determine the total
      phosphodiesterase activity in rat mast cells by means of specific and non
      specific inhibitors of phosphodiesterases. We used a fluorescent analogue of
      cAMP, 2'-O-anthraniloyl cAMP, the fluorescence intensity of which decreases when
      hydrolysed by phosphadiesterase (PDE), providing a measurement of total activity
      of PDE. The PDE inhibitors produced a decrease in the fluorescence fall.
      Therefore, we can establish that at least Type I, III, IV and probably Type V PDE
      are present in rat mast cells. We have also studied the effect of these PDE
      inhibitors on histamine release elicited by compound 48/80 and sodium fluoride.
      Chlorpromazine, a Type I PDE inhibitor, only slightly inhibits the fluoride
      evoked response, while, on the other hand, milrinone, a Type III PDE inhibitor,
      does not modify the response to compound 48/80.

PMID- 8562313
TI  - Thyroid stimulating hormone and N6-2'-O-dibutyryladenosine 3'-5'-cyclic
      monophosphate decrease 110,000-130,000 M(r) tyrosine-phosphorylated substrate in
      rat thyroid cells.
AB  - By immunoblotting using monoclonal antibodies against phosphotyrosine, thyroid
      stimulating hormone (TSH)-induced changes in tyrosine phosphorylation of
      intracellular proteins in earlier passages of rat thyroid cells (FRTL-5) were
      studied. TSH and N6-2'-O-dibutyryladenosine 3'-5'-cyclic monophosphate (Bt2cAMP)
      decreased the phosphotyrosine content of 110,000-130,000 M(r) substrate (p120) in
      parallel with a morphological change in FRTL-5 cells. Insulin-like growth factor
      I (IGF-I) or phorbol 12-myristate 13-acetate (PMA) only showed an attenuated
      reaction compared with that of TSH or Bt2cAMP. Further, sodium orthovanadate (a
      protein tyrosine phosphatase inhibitor) could not inhibit this reaction. These
      data suggest possible inhibitory effects of TSH and adenosine 3'-5'-cyclic
      monophosphate (cAMP) on tyrosine kinases that act on this substrate.

PMID- 8562314
TI  - Elevated intracellular cyclic AMP inhibits chemotaxis in human eosinophils.
AB  - Elevated intracellular cyclic AMP is associated with the inhibition of many
      inflammatory cellular responses. In this study, we examined the effect of cyclic
      AMP on eosinophil chemotaxis. Eosinophils were isolated from healthy human
      volunteers using an immunomagnetic method. Eosinophils were treated with agents
      that elevate intracellular cyclic AMP and evaluated for chemotactic responses to
      platelet-activating factor (PAF; 10(-6) M) and to complement factor 5a (C5a; 10(
      8) M) in microchemotaxis chambers. Forskolin, prostaglandin E1 (PGE1), and a
      phosphodiesterase (PDE) IV-selective inhibitor inhibited eosinophil chemotactic
      responses. The mean per cent inhibition of eosinophil chemotaxis in response to
      PAF by forskolin, PGE1, and the PDE IV-selective inhibitor (10(-5) M) was 16.8 +/
      5.3, 26.6 +/- 9.5, and 35.1 +/- 6.1%, respectively (n = 5). The corresponding
      values for C5a were 17.5 +/- 7.9, 20.8 +/- 10.7, and 39.5 +/- 5.0%. An exogenous
      cyclic AMP analogue (dibutyryl cyclic AMP, 10(-3) M) also inhibited eosinophil
      chemotaxis by 69.4 +/- 12.8 and 66.9 +/- 11.6% in response to PAF and C5a,
      respectively (n = 5). We conclude that elevated intracellular cyclic AMP inhibits
      eosinophil chemotaxis.

PMID- 8562315
TI  - Cellular expression of the Drosophila melanogaster FMRFamide neuropeptide gene
      product DPKQDFMRFamide. Evidence for differential processing of the FMRFamide
      polypeptide precursor.
AB  - DPKQDFMRFamide is one of five different FMRFamide-containing peptides encoded in
      the Drosophila FMRFamide gene. To study the cellular expression of
      DPKQDFMRFamide, we have generated antisera to DPKQD, the N-terminal sequence of
      the peptide, to avoid crossreactivity with other -FMRFamide-containing peptides.
      The antisera were purified and the specificity characterized. DPKQDFMRFamide
      immunoreactive material is first observed in the embryonic central nervous system
      (CNS) in one cell of the subesophageal ganglion and one cell in each of the three
      thoracic ganglia. This pattern of expression is observed in larval, pupal, and
      adult neural tissue, albeit with increased signal intensity. In larva, pupa, and
      adult, additional cells in the superior protocerebrum, a thoracic ganglion, and
      an abdominal ganglion express DPKQDFMRFamide immunoreactive material.
      Immunoreactivity is observed in a cell in the lateral protocerebrum of pupa and
      adult and cells in the optic lobe of adult. No immunoreactive material was
      observed in gut tissue. DPKQDFMRFamide antisera stain a subset of cells
      previously identified by in situ hybridization and immunocytochemistry to express
      the FMRFamide transcript and polypeptide precursor. These data suggest that the
      Drosophila FMRFamide polypeptide precursor undergoes differential processing to
      produce DPKQDFMRFamide immunoreactive material in a limited number of cells
      expressing the FMRFamide precursor.

PMID- 8562316
TI  - Seizures increase trkC mRNA expression in the dentate gyrus of rat hippocampus.
      Role of glutamate receptor activation.
AB  - In this study we have shown, by in situ hybridization and RNase protection assay,
      a significant trkC mRNA increase confined to the dentate gyrus of hippocampus,
      both after seizures induced by intracerebroventricular injection of kainic acid
      and bicuculline. Moreover, after bicuculline treatment we observed an earlier
      increase of trkC mRNA level, which peaked after 3 h and returned back to normal
      levels by 12 h. In contrast, the kainic acid treatment produced a delayed
      increase of trkC mRNA, which initiated after 6 h, peaked at 12 h, and returned to
      normal levels at 24 h. This increase, which involves also trkC mRNA receptor with
      tyrosine kinase activity, was mediated by non-NMDA receptors and counteracted by
      GABA potentiating agent diazepam. Using embryonic neuronal cultures from cerebral
      hemispheres, including hippocampus, we found that glutamate receptor agonists,
      including glutamate, kainate, NMDA, and t-ACPD, increase trkC mRNA levels with
      the following rank order of efficacy: NMDA > t-ACPD > kainic acid > glutamate. In
      conclusion, our data show that trkC mRNA expression in granule cells of the
      hippocampus dentate gyrus is increased during seizure activity and that it is
      mediated by non-NMDA receptors.

PMID- 8562317
TI  - Inhibition of beta A4 production by specific modulation of beta-secretase
      activity.
AB  - To study amyloid precursor protein (APP) processing we expressed different APP
      isoforms with and without the Swedish mutation and the membrane inserted C
      terminal 100 residues of APP (SPA4CT) in the human neuroblastoma cell line SY5Y.
      We show that expression of the Swedish mutation results in a significant
      production of the amyloidogenic intermediate A4CT, which is further processed by
      gamma-secretase leading to an overproduction of beta A4. Treatment with
      methylamine and ammonium chloride, inhibitors interfering with intracellular
      transport mechanisms, inhibits beta-secretase activity without influencing the
      physiological APP cleavage by alpha-secretase activity. By expressing SPA4CT, we
      demonstrate that secretion, but not generation, of beta A4 from SPA4CT is
      inhibited by methylamine resulting in intracellular beta A4. This provides
      experimental evidence for the intracellular localization of gamma-secretase
      activity and beta A4 generation.

PMID- 8562318
TI  - Cloning, pharmacological characterization, and anatomical distribution of a rat
      cDNA encoding for a galanin receptor.
AB  - We have cloned and expressed a rat cDNA, designated GALR1-rat, that encodes a
      galanin receptor based on homology, pharmacology, and anatomical criteria. This
      cDNA was isolated from a rat brain cDNA library. The nucleotide sequence of the
      cloned receptor revealed an open reading frame encoding a 346-amino-acid protein,
      showing 90.8% identity with the previously cloned human galanin receptor.
      Membranes prepared from COS cells transiently expressing GALR1-rat specifically
      bind 125I-galanin with high affinity (Kd = 0.12 +/- 0.01 nM). Rat, porcine, and
      human galanin were able to displace 125I-galanin with nanomolar Ki (0.08 +/-
      0.03, 0.10 +/- 0.01, and 0.14 +/- 0.03 nM, respectively), whereas the Ki values
      for the porcine galanin fragments galanin-(1-16), galanin-(2-29), and galanin-(3
      29) were 0.95 +/- 0.21 nM, 7.14 +/- 0.51 nM, and > 1 microM, respectively. The
      rank order potency of these ligands is consistent with that reported for the
      native galanin receptor. The distribution of the mRNA corresponding to the
      galanin receptor encoded by GALR1-rat was determined by in situ hybridization to
      rat brain sections. High levels of galanin receptor mRNA were detected in the
      ventral hippocampal formation, thalamic, amygdala, and medulla oblongata nuclei,
      and in the dorsal horn of the spinal cord.

PMID- 8562319
TI  - The influence of antiadhesion therapies on leukocyte subset accumulation in
      central nervous system ischemia in rats.
AB  - Although treatment with agents that block leukocyte function, including anti-ICAM
      1 and doxycycline, reduces experimental central nervous system (CNS) ischemic
      injury, it is not known how leukocyte subset accumulation is affected by these
      agents. Using the rat two-vessel occlusion model and immunohistochemistry, we
      investigated granulocyte (PMN) and monocyte/macrophage (M phi) accumulation at 1
      and 4 d postischemia. A total of 24 animals were randomized to sham surgery, or
      to ischemia with saline, anti-ICAM-1, or doxycycline treatments. No leukocytes
      were observed in sham animals. At 24 h postischemia, there was a moderate
      infiltration of PMN and M phi in untreated animals that was significantly
      decreased with either treatment. At 4 d after ischemia no PMN were identified,
      with extensive M phi accumulation occurring in untreated animals that was only
      partially reduced with doxycycline treatment. These results confirm that both
      anti-ICAM-1 and doxycycline treatments reduce PMN and M phi infiltration at 24 h.
      Delayed M phi accumulation occurs despite treatment, suggesting that some of
      these cells represent transformed resident microglia.

PMID- 8562320
TI  - Ontogenic expression of two alpha-1 adrenergic receptor subtypes in the rat
      brain.
AB  - alpha-1A/D and alpha-1B adrenergic receptor subtype mRNA expression was studied
      during pre- and postnatal rat brain development. Oligonucleotide probes were
      generated to distinguish these two homologous subtypes by in situ histochemical
      analysis in E14, E16, E19, P0, P8, P14, P21, and adult animals. alpha-1B
      adrenergic receptor mRNA expression was noted as early as the E14 animal and
      demonstrated specific regional and temporal expression. alpha-1A/D adrenergic
      receptor mRNA expression was limited in the E19 and P0 animal but increased in
      intensity with aging. Specific regional and temporal expression differed between
      the two subtypes. The regional localization for both subtypes appeared to be
      stable after P21 but the intensity of expression for both subtypes decreased
      between P21 and adulthood, which is a finding that correlates with previous
      ligand-binding data. Different subtypes of homologous receptors have very
      different ontogenic patterns of distribution and may account for previous
      discrepancies in ligand-binding data and differential tissue responses to various
      ligands during development.

PMID- 8562322
TI  - ODAC recommends full approval for Gemzar for pancreatic cancer.

PMID- 8562321
TI  - Comparison of the phosphorylation of myelin-associated glycoprotein in cultured
      oligodendrocytes and Schwann cells.
AB  - Phosphorylation of the large and small isoforms of myelin-associated glycoprotein
      (L- and S-MAG) was investigated in primary oligodendrocyte cultures and in
      immortalized Schwann cells by incubating the cells with inorganic [32P]phosphate
      and immunoprecipitating MAG. In oligodendrocytes, both L- and S-MAG were
      phosphorylated, but L-MAG was much more heavily labeled. In Schwann cells, most
      of the phosphorylation was in S-MAG, which is the predominant isoform expressed
      by these cells. In both types of cells, the principal phosphorylated amino acid
      in MAG was serine. Radioactive phosphothreonine and phosphotyrosine were also
      detected in the MAG from oligodendrocytes. In Schwann cells, there was less
      phosphorylation of threonine and labeled phosphotyrosine was not detected. In
      both oligodendrocytes and Schwann cells, the phosphorylation of MAG was
      stimulated by phorbol ester and a calcium ionophore, but not by forskolin. The
      results indicate that the phosphorylation of MAG is catalyzed by protein kinase C
      and possibly other calcium-activated kinases in both types of myelinating cells,
      but not by cAMP-activated kinase. An inhibitor of tyrosine phosphatase, ammonium
      vanadate, increased the amount of radioactive phosphate in MAG several fold in
      both oligodendrocytes and Schwann cells. However, even in the presence of
      vanadate, the great majority of radioactivity in MAG was in phosphoserine and
      only a small amount was in phosphotyrosine, suggesting that tyrosine
      phosphorylation of other proteins may indirectly increase the phosphorylation of
      MAG. The current status of our understanding of MAG phosphorylation is reviewed
      in the context of similarities and differences between our results and other
      reports in the literature.

PMID- 8562323
TI  - Locoregional therapies for early-stage prostate cancer.
AB  - Widespread use of prostate-specific antigen (PSA) as a screening tool has led to
      an increased incidence of biopsy-proven prostate cancer, as well as a shift
      toward more cases with clinically confined disease (stage T1 to T2). The two
      traditional therapeutic modalities, radical prostatectomy and external-beam
      radiation therapy, have undergone technical refinements. Other modalities, such
      as brachytherapy and cryosurgery, are also being used to treat early-stage
      disease. Comparisons between treatment results are difficult. Biochemical
      failure, based on PSA findings, is currently used to measure treatment efficacy,
      but the precise definition and clinical relevance of biochemical failure have yet
      to be established. The author presents current analyses of biochemical failure,
      cause-specific survival, distant metastasis, and morbidity rates following
      various treatment modalities.

PMID- 8562324
TI  - Clinical trials referral resource. Myelodysplastic syndromes.

PMID- 8562325
TI  - Inclusion of comorbidity in a staging system for head and neck cancer.
AB  - The widespread use of the TNM staging system has helped standardize the
      classification of cancers. Despite its excellence in describing a tumor's size
      and extent of anatomic spread, the TNM system does not account for the clinical
      biology of the cancer. Clinical factors, such as symptom severity, performance
      status, and comorbidity, which are important for classification, prognostication,
      and evaluation of treatment effectiveness, remain excluded from this system. In
      several studies of cancer prognosis, the presence of severe comorbidity was found
      to dramatically influence survival statistics and the evaluation of treatment
      effectiveness. A statistical technique known as conjunctive consolidation was
      used to incorporate comorbidity into the TNM staging system and maintain the four
      category system. Utilizing this technique, comorbidity was added to the TNM
      system for laryngeal cancer to create a composite staging system. Quantitative
      evaluation of the new system showed that the addition of comorbidity provides
      improved prognostic precision over TNM stage alone.

PMID- 8562326
TI  - Minimizing oral complications of cancer treatment.
AB  - Aggressive cancer therapy places patients at greater risk for oral complications
      and treatment-related consequences. Unfortunately, prevention and/or treatment of
      such oral sequelae have become often overlooked priorities of the treatment team.
      We describe a philosophy of management of the cancer patient that specifically
      emphasizes the prevention and treatment of oral complications associated with
      cancer therapy. These concepts and principles are based on treatment protocols
      and ongoing clinical practices at The University of Texas M. D. Anderson Cancer
      Center in Houston, Texas.

PMID- 8562327
TI  - Current status of endocrine therapy for metastatic breast cancer.
AB  - Hormonal manipulation is currently the mainstay of palliative care for metastatic
      breast cancer because it is well tolerated and produces significant responses in
      approximately one-third of unselected patients. Tamoxifen, a nonsteroidal
      antiestrogen, is currently considered first-line therapy. Second-line agents
      include progestins and aromatase inhibitors. New agents, such as the "pure"
      antiestrogens and the gonadotropin-releasing hormone (GnRH) agonists, are being
      tested. Other approaches for affecting the hormonal milieu are also under
      investigation, including combinations of hormonal agents, hormonal agents plus
      biologics, and hormonal agents plus antiproliferative agents. This review will
      address the basis for endocrine therapy and possible mechanisms of hormonal
      resistance, currently available agents and newer ones on the horizon, and areas
      of future interest.

PMID- 8562328
TI  - The 1995 Walter Hubert Lecture--molecular epidemiology of human cancer: insights
      from the mutational analysis of the p53 tumour-suppressor gene.

PMID- 8562329
TI  - Combined effects of an angiogenesis inhibitor (TNP-470) and hyperthermia.
AB  - TNP-470, a synthetic analogue of fumagillin first isolated from Aspergillus
      fumigatus, is known to be a potent anti-angiogenic compound. The combined effects
      on tumour growth and tumour angiogenesis of TNP-470 and hyperthermia were
      investigated. The tumour used was SCCVII carcinoma of the C3H/He mouse. The
      tumour response was evaluated by the tumour growth (TG) time assay. The TG time
      is the time required for one-half of the treated tumours to reach three times the
      initial tumour volume. Significant delay of tumour growth was observed by TNP-470
      alone (100 mg kg-1 x 2 or x 4), indicating that TNP-470 alone has antitumour
      effect in vivo. When TNP-470 (100 mg kg-1 x 2 or x 4) was administered after
      hyperthermia at 44 degrees C, the TG times of the combined treatment were
      significantly longer than those of heat alone (44 degrees C) or TNP-470 (100 mg
      kg-1 x 2 or x 4) alone. However, the TG time of combined treatment with TNP-470
      and hyperthermia at 42 degrees C was quite similar to that of TNP-470 alone. This
      conflicting result on the combined effect of TNP-470 and hyperthermia may be
      related to the temperature-dependent vascular damage by hyperthermia. Dose
      dependent inhibition of angiogenesis by TNP-470 was demonstrated in
      microangiograms obtained 4 days and 7 days after hyperthermia (44 degrees C for
      30 min). It is, thus, suggested that the combined effect of TNP-470 and
      hyperthermia is attributable to the inhibition of angiogenesis by TNP-470
      following heat-induced vascular damage.

PMID- 8562330
TI  - The angiogenic factor platelet-derived endothelial cell growth factor/thymidine
      phosphorylase is up-regulated in breast cancer epithelium and endothelium.
AB  - Tumour angiogenesis is a complex multistep process regulated by a number of
      angiogenic factors. One such factor, platelet-derived endothelial cell growth
      factor has recently been shown to be thymidine phosphorylase (TP). TP catalyses
      the reversible phosphorylation of thymidine to deoxyribose-1-phosphate and
      thymine. Although known to be generally elevated in tumours, the expression of
      this enzyme in breast carcinomas is unknown. Therefore, we used ribonuclease
      protection assays and immunohistochemistry to examine the expression of TP in 240
      primary breast carcinomas. Nuclear and/or cytoplasmic TP expression was observed
      in the neoplastic tumour epithelium in 53% of tumours. Immunoreactivity was also
      often present in the stromal, inflammatory and endothelial cell elements.
      Although endothelial cell staining was usually focal, immunoreactivity was
      observed in 61% of tumours and was prominent at the tumour periphery, an area
      where tumour angiogenesis is most active. Tumour cell TP expression was
      significantly inversely correlated with grade (P = 0.05) and size (P = 0.003) but
      no association was observed with other tumour variables. These findings suggest
      that TP is important for remodelling the existing vasculature early in tumour
      development, consistent with its chemotactic non-mitogenic properties, and that
      additional angiogenic factors are more important for other angiogenic processes
      like endothelial cell proliferation. Relapse-free survival was higher in node
      positive patients with elevated TP (P = 0.05) but not in other patient groups.
      This might be due to the potentiation of chemotherapeutic agents like
      methotrexate by TP. Therefore, this enzyme might be a prediction marker for
      response to chemotherapy.

PMID- 8562331
TI  - Activation of methotrexate-phenylalanine by monoclonal antibody--carboxypeptidase
      A conjugate for the specific treatment of ovarian cancer in vitro.
AB  - Monoclonal antibody 4E3 directed against a glycosylated surface protein on human
      ovarian teratocarcinoma cells (CRL-1572 cell line) was conjugated to bovine
      carboxypeptidase A (CPA) using a 3400 Da polyethylene glycol chain bearing an N
      hydroxysuccinimide group at both ends. The conjugate preparation was purified by
      fast protein liquid chromatography on a Superose 12/30 HR column. The 4E3-CPA
      conjugate was recovered in the third fraction by SDS-PAGE analysis. The specific
      binding of the 4E3-CPA conjugate to CRL-1572 cells was confirmed by a FACS
      analysis and the enzymatic activity of the conjugate remained while tested with
      hippuryl-L-phenylalanine. In vitro cytotoxic assays on CRL-1572 cells showed that
      the prodrug methotrexate-phenylalanine (MTX-Phe) alone was non-toxic (ID50 > 1000
      ng ml-1) but was selectively converted to MTX when the cells were pretreated with
      50 micrograms ml-1 4E3-CPA conjugate, which enhanced considerably the
      pharmacological activity of the prodrug with an ID50 of 70 ng ml-1. The co
      culture assays with CRL-1572 and MRC-5 cells (human normal lung diploid
      fibroblast cell lines) demonstrated the specificity of the 4E3-CPA conjugate for
      the CRL-1572 cells since no cytotoxicity was observed on the MRC-5 cells. When
      both cell lines were mixed in ratios ranging from 1:10,000 to 1:5 (CRL-1572:MRC
      5), the significant increase in the ID25 was correlated with the proportion of
      tumoral cells present in the cell inoculum. These results suggest that MTX-Phe
      combined with 4E3-CPA conjugate is a promising model for a more selective and
      localised anti-cancer chemotherapy based on the ADEPT concept.

PMID- 8562332
TI  - Vascular perfusion and hypoxic areas in RIF-1 tumours after photodynamic therapy.
AB  - The influence of photodynamic therapy (PDT) on vascular perfusion and the
      development of hypoxia was investigated in the murine RIF-1 tumour. Image
      analysis was used to quantify changes in perfusion and hypoxia at 5 min after
      interstitial Photofrin-mediated PDT. The fluorescent stain Hoechst 33342 was used
      as an in vivo marker of functional vascular perfusion and the antibody anti
      collagen type IV as a marker of the tumour vasculature. The percentage of total
      tumour vasculature that was perfused decreased to less than 30% of control values
      after PDT. For the lower light doses this decrease was more pronounced in the
      centre of the tumour. The observed reduction in vascular perfusion showed a good
      linear correlation (r = 0.98) with previously published tumour perfusion data
      obtained with the 86Rb extraction technique. The image analysis technique
      provides extra information concerning the localisation of (non)-perfused vessels.
      To detect hypoxic tumour areas in vivo, an immunohistochemical method was used
      employing NITP [7-(4'-(2-nitroimidazol-1-yl)-butyl)-theophylline]. A large
      increase in hypoxic areas was found for PDT-treated tumours. More than half the
      total tumour area was hypoxic after PDT, compared with < 4% for control tumours.
      Our studies illustrate the potential of image analysis systems for monitoring the
      functional consequences of PDT-mediated vascular damage early after treatment.
      This provides direct confirmation that the perfusion changes lead to tissue
      hypoxia, which has implications for the combined treatment of PDT with
      bioreductive drugs.

PMID- 8562333
TI  - Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected
      non-small-cell lung cancer.
AB  - Amplification of the CCDN1 gene encoding cyclin D1 was examined by Southern
      blotting and multiplex polymerase chain reaction (PCR) and occurred in 8 of 53
      patients (15%) with primary resected non-small-cell lung cancer (NSCLC). These
      tumours and 17 additional tumours with a normal gene copy number showed
      overexpression of cyclin D1 (25/53, 47%), as assessed by immunostaining using a
      monoclonal antibody. In 22/25 cases, cyclin D1 was localised in the cytoplasm,
      but some (7/25) had simultaneous nuclear staining. This result is in marked
      contrast to that reported in breast, hepatocellular and colorectal carcinoma
      studies where immunostaining was invariably nuclear. Examination of a restriction
      fragment length polymorphic (RFLP) site within the 3'untranslated region of the
      cDNA following reverse transcriptase (RT)-PCR (29/53 informative cases) showed a
      strong association between cytoplasmic staining and imbalance in allele-specific
      message levels. Cyclin D1 overexpression was associated with a poorly
      differentiated histology (P = 0.04), less lymphocytic infiltration of the tumour
      (P = 0.02) and a reduction in local relapse rate (P = 0.01). The relative risk of
      local relapse was 9.1 in tumours without cyclin D1 overexpression (P = 0.01, Cox
      regression analysis). We conclude that genetic alteration of cyclin D1 is a key
      abnormality in lung carcinogenesis and may have diagnostic and prognostic
      importance in the treatment of resectable NSCLC.

PMID- 8562334
TI  - The prognostic value of epidermal growth factor receptor mRNA expression in
      primary ovarian cancer.
AB  - The expression of mRNA for the epidermal growth factor (EGF) receptor, EGF and
      transforming growth factor alpha (TGF-alpha) was determined in 76 malignant, six
      borderline and 15 benign primary ovarian tumours using the reverse transcriptase
      polymerase chain reaction and related to clinical and pathological parameters. Of
      the malignant tumours, 70% (53/76) expressed EGF receptor mRNA, 31% (23/75)
      expressed EGF mRNA and 35% (26/75) expressed TGF-alpha mRNA. For the borderline
      tumours, four of six (67%) expressed EGF receptor mRNA, 1/6 (17%) expressed TGF
      alpha mRNA and none expressed EGF mRNA. Finally, 33% (5/15) of the benign tumours
      expressed EGF receptor mRNA, whereas 40% (6/15) expressed EGF mRNA and 7% (1/15)
      expressed TGF-alpha mRNA. The presence of the EGF receptor in malignant tumours
      was associated with that of TGF-alpha (P = 0.0015) but not with EGF (P = 1.00),
      whereas there was no relationship between the presence of EGF and TGF-alpha (P =
      1.00). EGF receptor mRNA expression was significantly and positively associated
      with serous histology (P = 0.006) but not with stage or grade. Neither EGF nor
      TGF-alpha showed any link with histological subtype or stage. The survival of
      patients with malignant tumours possessing EGF receptor mRNA was significantly
      reduced compared with that of patients whose tumours were negative (P = 0.030 for
      all malignant tumours; P = 0.007 for malignant epithelial tumours only). In
      contrast, neither the expression of TGF-alpha nor EGF was related to survival.
      These data suggest that the presence of EGF receptor mRNA is associated with poor
      prognosis in primary ovarian cancer.

PMID- 8562335
TI  - Regulation of P-glycoprotein 1 and 2 gene expression and protein activity in two
      MCF-7/Dox cell line subclones.
AB  - The MCF-7 doxorubicin-resistant cell line MCF-7/Dox has been used extensively for
      studies of the multidrug resistance phenomenon. Using fluorescence-activated cell
      sorting (FACS), these cells were separated into two populations on the basis of
      rhodamine 123 (R123) accumulation. We designated these as low P-glycoprotein (LP
      gp) and high P-gp (HP-gp) cells on the basis of their P-gp content. Using the
      reverse transcriptase polymerase chain reaction technique controlled by
      homologous internal standards, we analysed levels of MDR1 and MDR2 mRNA in each
      cell type. LP-gp and HP-gp cells had MDR1 mRNA levels of 2.17 +/- 0.17 and 6.65
      +/- 2.29 amol ng-1 total RNA respectively, compared with 0.00088 +/- 0.00005 amol
      ng-1 in wild-type MCF-7 cells (MCF-7/WT). MCF-7/WT cells additionally contained
      0.023 +/- 0.016 amol ng-1 of MDR2 mRNA, which was unchanged in LP-gp cells, but
      lower than in HP-gp cells, which contained 0.42 +/- 0.08 amol ng-1. Both LP-gp
      and HP-gp cells contained increased copies of the MDR1 gene. However, the degree
      of gene amplification did not correlate with the changes in MDR1 mRNA levels,
      indicating further regulatory levels of gene expression. The level of P-gp
      detected by MRK 16 correlated with R123 accumulation. HP-gp cells expressed a 10
      fold higher level of P-gp1 than LP-gp cells. However, there was only a 3-fold
      increase in MDR1 mRNA level in HP-gp cells compared with LP-gp cells. These data
      suggest that some regulation of P-gp1 expression also occurred at the post
      translational level. Phosphorylation of P-gp by protein kinase C (PKC)-alpha is
      necessary for its activity. Our analysis of PKC-alpha, 0 and epsilon isozyme
      levels, and subcellular distribution, shows a co-regulation of expression with P
      gp, suggesting a necessary role for PKC in P-gp regulation.

PMID- 8562337
TI  - The effects of beta-human chorionic gonadotrophin on the in vitro growth of
      bladder cancer cell lines.
AB  - The effects of human chorionic gonadotrophin (hCG) and its subunits on in vitro
      bladder cancer cell growth have been assessed using the a tetrazolium salt
      reduction assay (MTT). Intact hCG, alpha-hCG and beta-core hCG all had no effect
      on cell growth, while beta-hCG increased MTT reduction in all four bladder cancer
      lines tested. The magnitude of beta-hCG stimulation was maximal in the T24 line,
      which does not itself produce beta-hCG and appeared to be correspondingly lower
      in beta-hCG-secreting lines. The addition of antibodies to beta-hCG inhibited MTT
      reduction among high secretors but failed to inhibit MTT reduction in non-beta
      hCG producers. These results are consistent with the poor prognosis associated
      with beta-hCG expression by bladder tumours in vivo and suggest an
      autocrine/paracrine stimulation of tumour growth by endogenously produced beta
      hCG.

PMID- 8562336
TI  - Effect of transient expression of the oestrogen receptor on constitutive and
      inducible CYP1A1 in Hs578T human breast cancer cells.
AB  - Hs578T human breast cancer cells are an oestrogen receptor (ER)-negative cell
      line. Treatment of these cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      resulted in formation of a 6.9 S nuclear aryl hydrocarbon (Ah) receptor complex,
      which bound to a [32P]dioxin-responsive element in a gel electrophoretic mobility
      shift assay. However, TCDD does not induce CYP1A1 gene expression or
      chloramphenicol acetyl transferase (CAT) activity in cells transiently
      transfected with pRNH11c or pMCAT5.12, which are Ah-responsive plasmids derived
      from the 5'-flanking region of the human and murine CYP1A1 genes respectively.
      Restoration of Ah responsiveness was investigated by co-transfecting Hs578T cells
      with pRNH11c or pMCAT5.12 and plasmids that express the ER (hER), Ah receptor
      (AhR) and AhR nuclear translocator (Arnt) proteins. ER expression resulted in
      significantly increased basal CAT activity; however, TCDD did not induce CAT
      activity in the transiently transfected cells. Expression of the AhR or Arnt
      proteins did not alter basal or inducible CAT activity. Expression of N- or C
      terminal truncated ER in Hs578T resulted in differential regulation of Ah
      responsiveness. In Hs578T cells transiently expressing the ER, which contains C
      terminal deletions (amino acids 282-595), basal CAT activity was also increased;
      however, Ah responsiveness was not restored. In contrast, transient expression of
      N-terminal-deleted (amino acids 1-178) ER resulted in a marked decrease in basal
      CAT activity but a restoration of Ah responsiveness. These results suggest that
      basal and inducible CAT activity in Hs578T cells transiently transfected with
      pRNH11c is modulated differentially by ER domains that are present in the N- and
      C-terminal regions of the ER.

PMID- 8562338
TI  - Correlation between integrin alpha 5 expression and the malignant phenotype of
      transitional cell carcinoma.
AB  - We examined the expression of alpha 1, alpha 2, alpha 3, alpha 4, alpha 5 and
      beta 1 integrin on 36 transitional cell cancers (TCCs) in the bladder by
      immunohistochemistry. Only alpha 2, alpha 3 and beta 1 were detected on normal
      transitional cell epithelium, but four TCCs (12.5%) revealed positive staining
      for alpha 1, seven (19.4%) for alpha 4 and seven (20%) for alpha 5. These altered
      expressions of integrin alpha chain were more frequent in histologically higher
      stage or grade of TCC, and a correlation was found between increased alpha 5
      expression and histological stage. alpha 5 was positive in 6 (35.3%) of 17
      invasive TCCs whereas only 1 (5.9%) of 17 superficial TCCs. Flow cytometric
      analysis on bladder cancer cell lines showed that T24 and HT1376, which are
      undifferentiated TCC cell lines, highly expressed alpha 5 and beta 1. Also,
      SCaBER, which is derived from urinary bladder squamous cell cancer and which is
      recognised as the most malignant phenotype after metaplasia of transitional
      epithelium, had alpha 5 and beta 1. However, RT4, which is derived from
      transitional cell papilloma, showed no expression of alpha 5. Furthermore,
      reverse transcriptase-polymerase chain reaction (RT-PCR) showed the presence of
      mRNA of alpha 5 on T24, SCaBER and HT1376, but not on RT4. Taken together, it
      seems that the presence of alpha 5 integrin might be a more malignant phenotype
      in transitional cell carcinoma.

PMID- 8562339
TI  - The sensitivity of normal brain and intracranially implanted VX2 tumour to
      interstitial photodynamic therapy.
AB  - The applicability and limitations of a photodynamic threshold model, used to
      describe quantitatively the in vivo response of tissues to photodynamic therapy,
      are currently being investigated in a variety of normal and malignant tumour
      tissues. The model states that tissue necrosis occurs when the number of photons
      absorbed by the photosensitiser per unit tissue volume exceeds a threshold. New
      Zealand White rabbits were sensitised with porphyrin-based photosensitisers.
      Normal brain or intracranially implanted VX2 tumours were illuminated via an
      optical fibre placed into the tissue at craniotomy. The light fluence
      distribution in the tissue was measured by multiple interstitial optical fibre
      detectors. The tissue concentration of the photosensitiser was determined post
      mortem by absorption spectroscopy. The derived photodynamic threshold values for
      normal brain are significantly lower than for VX2 tumour for all photosensitisers
      examined. Neuronal damage is evident beyond the zone of frank necrosis. For
      Photofrin the threshold decreases with time delay between photosensitiser
      administration and light treatment. No significant difference in threshold is
      found between Photofrin and haematoporphyrin derivative. The threshold in normal
      brain (grey matter) is lowest for sensitisation by 5 delta-aminolaevulinic acid.
      The results confirm the very high sensitivity of normal brain to porphyrin
      photodynamic therapy and show the importance of in situ light fluence monitoring
      during photodynamic irradiation.

PMID- 8562340
TI  - Mutational analysis of the CDKN2 gene in metastases from patients with cutaneous
      malignant melanoma.
AB  - We analysed 26 metastases from 25 patients with sporadic cutaneous malignant
      melanoma for alterations in the CDKN2 gene by a combined polymerase chain
      reaction/single-strand conformation polymorphism (PCR/SSCP)/nucleotide sequencing
      approach. Eleven alterations (one in exon 1, five in exon 2 and five in the 3'
      non-coding sequence of the exon 3 region) were concordantly and independently
      detected by both SSCP and nucleotide sequence analysis. Two of the exon 2 changes
      and the five changes in the non-coding exon 3 region are likely to represent
      natural polymorphism. Four (15%) of 26 metastases thus had CDKN2 mutations and
      belonged to 3 (12%) of 25 patients. Semi-quantitative PCR furthermore revealed no
      sign of homozygous deletions of the CDKN2 exon 2 region. The results support an
      involvement of the CDKN2 product in the development of a subgroup of sporadic
      melanomas and encourage the search for alterations in additional genes of the
      9p21 region.

PMID- 8562341
TI  - The absence of autonomic perivascular nerves in human colorectal liver
      metastases.
AB  - The peptidergic/aminergic innervation of normal liver and tumour blood vessels
      was investigated in order to determine vascular control with a view to improving
      the efficacy of hepatic arterial cytotoxic infusion in the treatment of
      colorectal liver metastases. Selected areas of liver metastases and
      macroscopically normal liver from resection specimens (n = 13) were studied using
      light microscope immunohistochemistry for the presence of protein gene product
      9.5 (PGP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY),
      calcitonin gene-related peptide (CGRP), substance P (SP) and tyrosine hydroxylase
      (TH). The ultrastructure of blood vessels supplying liver metastases and their
      perivascular innervation were also examined by transmission electron microscopy.
      In the normal liver, perivascular immunoreactive nerve fibres containing PGP, NPY
      and TH were observed around the interlobular blood vessels and along the
      sinusoids and the central vein of the hepatic lobule. The greatest density of
      immunoreactive nerve fibres was seen for PGP, followed (in decreasing order) by
      NPY and TH. VIP, SP and CGRP immunoreactivity was observed only in nerve bundles
      associated with the large interlobular blood vessels. In contrast, no
      perivascular immunoreactive nerves were observed in colorectal liver metastases.
      Electron microscopy confirmed the absence of perivascular nerves in liver
      metastases. In addition, it showed that the walls of these blood vessels were
      composed of a layer of endothelial cells surrounded by an incomplete or, very
      rarely in the periphery of the tumour, a complete, layer of synthetic phenotype
      of smooth muscle-like cells. These results imply that the blood vessels supplying
      liver metastases are bereft of normal neuronal regulation; whether there is a
      role for endothelial cell control of blood flow in these vessels is not yet
      known.

PMID- 8562342
TI  - Isolation and characterisation of Kasumi-1 human myeloid leukaemia cell line
      resistant to tumour necrosis factor alpha-induced apoptosis.
AB  - Tumour necrosis factor (TNF)-alpha induces apoptosis in a human acute myeloid
      leukaemia cell line, Kasumi-1. To examine the role of protein phosphorylation in
      signal transduction of TNF-alpha-induced apoptosis, a variant cell line resistant
      to TNF-alpha was established by an intermittent challenge of Kasumi-1 cells with
      increasing concentrations of TNF-alpha for 6 months. The mechanism of resistance
      to TNF-alpha appears to be in the post-receptor pathway because expression of p55
      TNF receptor in the variant cells is increased compared with that of the parental
      Kasumi-1 cells. In renaturation assays, TNF-alpha induced a rapid activation of
      different protein kinases of different molecular weights, including the 50 kDa
      protein kinase (PK50) followed by the 35 kDa protein kinase (PK35), in the
      parental Kasumi-1 cells. The dose-response of TNF-alpha required to activate PK50
      and PK35 was closely related to concentrations of TNF-alpha that induced
      apoptosis. Treatment of Kasumi-1 cells with ceramide also activated PK35. In TNF
      resistant variant cells, activation of PK35 in response to TNF-alpha or ceramide
      was practically nil. These findings suggest that activation of PK35 through the
      ceramide pathway may play an important role in signal transduction of TNF-alpha
      in the Kasumi-1 cell line, while the decreased activation of PK35 may explain the
      insensitivity of the variant cells towards TNF-alpha.

PMID- 8562343
TI  - LOH at 3p correlates with a poor survival in oral squamous cell carcinoma.
AB  - We analysed chromosome 3p for loss of heterozygosity (LOH) in 48 primary oral
      squamous cell carcinomas (SCCs) using 15 markers and constructed a deletion map
      for this chromosome arm. LOH at one or more loci was found in 34/48 (71%) of
      tumours. The data support the existence of at least three distinct regions of
      deletion at 3p24-26, 3p21.3-22.1 and 3p12.1-14.2. A significant correlation was
      observed between the number of regions showing allele loss at 3p and tumour
      stage, consistent with the progressive accumulation of genetic errors during the
      development of oral SCC. There were also significant associations between LOH at
      3p and disease-free and overall survival of patients with early stage disease.
      This study is the first to demonstrate the prognostic significance of LOH at 3p
      for oral cancer and may help to identify patients who should receive more
      aggressive treatment.

PMID- 8562344
TI  - Comparative study of CA242 and CA19-9 in chronic pancreatitis.
AB  - CA242 has been proved to be useful in the diagnosis of pancreatic cancer. The aim
      of the present study was to clarify the mechanisms contributing to the high
      specificity of CA242 as compared with CA19-9 resulting from scarce serum
      elevation of this antigen in patients with chronic pancreatitis by correlating
      serum levels and endoscopic retrograde choledocho-pancreatography (ERCP) findings
      and by immunohistochemical analysis. Serum CA19-9 levels were significantly
      elevated in patients with calcification and with main pancreatic duct (MPD)
      stenosis or obstruction. On the other hand, serum CA242 levels showed no
      significant elevation in patients with such factors. Even though such
      pathological conditions were considered to lead to the stagnation of pancreatic
      juice, serum CA242 levels seemed to be less affected than serum CA19-9 levels.
      Immunohistochemical studies of chronic pancreatitis tissues revealed that CA242
      was expressed less frequently and less intensely than CA19-9, and the difference
      in expression was more prominent in the centroacinar cells and terminal ductules.
      From the results of the present study, it is conceivable that CA242 is less
      influenced by the stagnation of the pancreatic juice than CA19-9 because of the
      low levels of expression in ductal systems, which results in the release of this
      antigen into the circulation in lower amounts than that of CA19-9.

PMID- 8562345
TI  - Hepatocyte growth factor/scatter factor is present in most pleural effusion
      fluids from cancer patients.
AB  - Pleural effusion samples were obtained from 55 patients with malignant disease,
      including patients with primary lung cancers and those with a variety of other
      tumours metastatic to the pleura. The effusions were assayed for the presence of
      hepatocyte growth factor/scatter factor (HGF/SF), by both ELISA and bioassay. The
      presence of malignant cells in the effusions was also assessed. Detectable
      amounts of the factor, as judged by both criteria, were found in over 90% of all
      the effusions, including those from patients with a wide variety of carcinomas
      and also lymphomas. A wide range of HGF/SF levels were found for all tumour
      classes, some effusions containing high levels above 4 ng ml-1. It is concluded
      that tumours within the pleura and adjacent lung tissue are usually exposed to
      biologically significant levels of HGF/SF.

PMID- 8562346
TI  - Prognosis of younger and older patients with early breast cancer.
AB  - The use of mammography in recent years has resulted in an increase in the
      detection of small breast cancers. The beneficial effects of early detection on
      breast cancer mortality seem to differ with age. To obtain more insight into this
      matter we studied the long-term prognosis of patients with early invasive breast
      cancers (T1) in three age groups: 144 patients of age 40-49, 402 patients of age
      50-69 and 192 patients 70 years or older at diagnosis. In all age groups,
      patients with a tumour of 1 cm or less have a longer breast cancer specific
      survival than patients with a tumour larger than 2 cm. The survival advantage in
      the case of tumours of a size rounded to 1.5 cm compared with tumours larger than
      2 cm in the under age 50 group was marginal (and not significant). However, older
      patients with tumours of this size do have a significantly improved survival. It
      is more difficult to improve survival in younger patients through early
      detection, partly because of an apparent early metastatic potential of their
      tumours. A reduction in breast cancer mortality might be expected in women
      younger than 50 years of age only if a substantial proportion of the invasive
      cancers are detected before their size exceeds 1 cm.

PMID- 8562347
TI  - Creatine kinase BB isoenzyme levels in tumour cytosols and survival of breast
      cancer patients.
AB  - Creatinine kinase BB (CK-BB) is elevated in many tumours including those of the
      breast. We have recently described a new, highly sensitive and specific method
      for measuring CK-BB, based on monoclonal antibodies and time-resolved
      fluorometry. Using this method, we quantitated CK-BB in 172 breast tumour
      cytosols and examined the associations between CK-BB and other
      clinicopathological variables and patient survival. High CK-BB levels were seen
      more frequently in tumours from patients who were younger (age < 50 years),
      patients who qualified for chemotherapy and patients with oestrogen receptor
      positive tumours. No association was seen between CK-BB and tumour stage, grade,
      size, histological type or the progesterone receptor. In univariate analysis, the
      risk of relapse or death was higher in the group with tumours containing high CK
      BB levels but the difference did not reach statistical significance. In
      multivariate analysis, the risk of death was statistically significantly higher
      in the high-CK-BB group. Analysis of subsets of patients revealed that patients
      with oestrogen receptor-negative cancer have higher risk of death if their
      tumours contain high levels of CK-BB. Our data suggest that, in general, CK-BB is
      associated with more aggressive tumours but its value as a prognostic indicator
      is limited. CK-BB content of breast tumours may be more useful as an aid in
      selecting therapy directed at inhibiting this enzyme activity and thus depriving
      tumour cells of their energy source.

PMID- 8562348
TI  - Phase II study of continuous infusional 5-fluorouracil with epirubicin and
      carboplatin (instead of cisplatin) in patients with metastatic/locally advanced
      breast cancer (infusional ECarboF): a very active and well-tolerated outpatient
      regimen.
AB  - Infusional 5-fluorouracil (F) with cisplatin (C) and epirubicin (E), so-called
      infusional ECF, is a highly active new schedule against locally advanced or
      metastatic breast cancer. Cisplatin, however, is a major contributor to toxicity
      and usually requires inpatient treatment. In an attempt to overcome this, we have
      investigated the effect of substituting carboplatin for cisplatin in our original
      infusional ECF regimen. Fifty-two patients with metastatic (n = 36) or locally
      advanced/inflammatory (n = 16) breast cancer were treated with 5-fluorouracil 200
      mg m-2 day-1 via a Hickman line using an ambulatory pump for for 6 months, with
      epirubicin 50 mg m-2 intravenously (i.v.) and carboplatin AUC5 i.v. every 4
      weeks, for six courses (infusional ECarboF). The overall response rate (complete
      plus partial) was 81% (95% CI 67%-90%), with a complete response rate of 17% (95%
      CI 6-33%) in patients with metastatic disease and 56% (95% CI 30-80%) in patients
      with locally advanced disease. Median response duration and survival for
      metastatic disease was 8 and 14 months respectively, and two patients with
      locally advanced disease have relapsed. These results are very similar to those
      previously achieved with infusional ECF. Severe grade 3/4 toxicity was low.
      Infusional ECarboF is a highly active, well-tolerated, outpatient regimen
      effective against advanced/metastatic breast cancer and now warrants evaluation
      against conventional chemotherapy in high-risk early breast cancer.

PMID- 8562349
TI  - Phase II clinical trials with rhizoxin in breast cancer and melanoma. The EORTC
      Early Clinical Trials Group.
AB  - Rhizoxin is a new anti-tumour agent isolated from the pathogenic fungus Rhizopus
      chinensis. It has shown broad activity against murine tumour models and is also
      active against vinca alkaloid-resistant cells. The purpose of our studies was to
      determine the clinical activity of this compound in patients with advanced breast
      cancer and melanoma. Based on the results of a phase I study, 2.0 mg m-2 was
      administered as intravenous infusion over 5 min every 21 days. Nineteen patients
      were entered into the breast cancer phase II trial and received a total of 50
      courses (median 2, range 1-6). Of these, dose reductions were performed in three
      courses because of leucopenia or stomatitis (1.5 mg m-2, one course; 1.45 mg m-2,
      two courses). Twenty-six patients were entered into the melanoma trial and
      received a total of 70 courses (median 2, range 1-12). No dose reductions were
      required. All patients were eligible for toxicity. Haematological toxicity
      included neutropenia CTC grade 3 (29/120 courses, 24.2%) and grade 4 (11/20
      courses, 9.2%). Only drug-related CTC grade 1 thrombocytopenia was observed. Non
      haematological toxicity included alopecia in all patients after two courses of
      treatment as well as CTC grade 3/4 stomatitis and asthenia. In the breast cancer
      study, one patient achieved a more than 50% tumour reduction after six cycles but
      was progressing after 6 weeks. Another patient showed a partial remission after
      the first course but was taken off the study because of CTC grade 3 skin
      toxicity. One patient was not evaluable for response (early death). No objective
      remissions were observed in 15 evaluable patients. In melanoma, no objective
      remissions were observed. We conclude that rhizoxin can be safely administered at
      2.0 mg m-2 every 3 weeks. However, it has little activity in patients with
      advanced breast cancer and melanoma.

PMID- 8562350
TI  - Phase II study of rhizoxin in squamous cell head and neck cancer. The EORTC Early
      Clinical Trials Group.
AB  - To test the anti-tumour activity of rhizoxin in recurrent and/or metastatic
      squamous cell head and neck cancer, we performed a phase II study. Eligibility
      required histologically proven squamous cell head and neck cancer. Patients could
      only have received one prior chemotherapy. Patients were entered if WHO PS was <
      or = 2 and organ functions were normal. Treatment consisted of rhizoxin 1.5-2.0
      mg m-2 i.v. bolus injection once every 3 weeks. Thirty-two patients entered the
      study. All were eligible, 31 were evaluable for toxicity and 25 for response.
      Toxicity mainly consisted of pain at the tumour site and leucocytopenia. Mild
      asthenia and stomatitis were also observed. Two objective partial responses,
      lasting 7.5 and 3.5 months, were seen. Rhizoxin at this dose and schedule has
      minor activity in recurrent and/or metastatic squamous cell head and neck cancer.

PMID- 8562351
TI  - Single agent activity of rhizoxin in non-small-cell lung cancer: a phase II trial
      of the EORTC Early Clinical Trials Group.
AB  - In a multicentre trial of the EORTC-Early Clinical Trials Group (ECTG) we treated
      31 chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC)
      with rhizoxin, a novel tubulin-binding agent. The drug was given as an i.v. bolus
      injection at 2 mg m-2 once every 3 weeks in an outpatient setting. Prophylactic
      antiemetics were not routinely given. Of the 29 eligible patients, nine had been
      treated surgically and three had received radiotherapy. The main toxic effects
      observed were stomatitis (34% of cycles) and neutropenia (41% of cycles).
      Neutropenic fever was rare (3% of cycles). Twenty-seven patients were evaluable
      for response. There were four partial responses (15%), while 13 patients (48%)
      showed stabilisation of their disease. The median duration of response was 7
      months (range 6.0-10.7 months) and median survival from the start of rhizoxin
      treatment was 6 months (range 2-14.7 months). Rhizoxin as single agent shows
      activity in patients with advanced NSCLC.

PMID- 8562352
TI  - Randomised trial of four-drug vs less intensive two-drug chemotherapy in the
      palliative treatment of patients with small-cell lung cancer (SCLC) and poor
      prognosis. Medical Research Council Lung Cancer Working Party.
AB  - This randomised trial was conducted to compare a four-drug chemotherapy regimen
      as a control vs a less intensive two-drug regimen in terms of quality of life
      (QL), tumour response and survival in the palliative treatment of patients with
      small-cell lung cancer (SCLC) and poor prognosis. A total of 310 patients with
      extensive SCLC or limited disease but poor performance status were allocated at
      random to two chemotherapy regimens, each given on 3 consecutive days at 3 week
      intervals for three cycles: etoposide, cyclophosphamide, methotrexate and
      vincristine (ECMV, 154 patients) or etoposide and vincristine (EV, 156 patients).
      QL was assessed by patients using the Rotterdam Symptom Checklist, the Hospital
      Anxiety and Depression Scale and a daily diary card. Specific disease- and
      treatment-related symptoms were recorded by clinicians. The levels of palliation
      were high and similar in the two groups, although the ECMV regimen was on balance
      superior in palliating physical symptoms and reducing psychological distress. The
      EV regimen caused less toxicity, particularly mucositis, which, using Kaplan
      Meier curves, occurred in an estimated 34% of patients compared with 54% in the
      ECMV group. The estimated rates of WHO grade 2 or worse haematological toxicity
      were 21% in the EV compared with 38% in the ECMV patients. There was no overall
      difference in response or survival; the median survival periods were 141 days in
      the ECMV group and 137 in the EV group and the survival rates 37% and 38% at 6
      months and 12% and 10% at 1 year respectively. Nevertheless, 37 ECMV patients
      died within 3 weeks of starting the first cycle of chemotherapy (24 of them
      during the 2nd week) compared with 18 (9) EV patients. The EV regimen is a useful
      palliative regimen for patients with SCLC and poor prognosis.

PMID- 8562353
TI  - Traumas and tests in the great outdoors.

PMID- 8562355
TI  - The challenge of change.

PMID- 8562354
TI  - Express delivery.

PMID- 8562356
TI  - How to use instant relaxation methods.
AB  - Relaxation methods can be used by nurses to help patients suffering from stress
      related to their illness. Nurses can also use the methods themselves to relieve
      tension related to their work. This article describes how to carry out simple
      techniques 'on the spot'.

PMID- 8562357
TI  - Mental health. Introducing training for care assistants.

PMID- 8562359
TI  - Round the reforms.

PMID- 8562358
TI  - Bionursing: signs of iron deficiency.
AB  - In the ninth article in our series on bionursing, the authors explain how an
      understanding of physiology can help nurses to identify the common signs and
      symptoms of iron deficiency and ensure patients receive prompt and appropriate
      treatment.

PMID- 8562360
TI  - Reminiscence therapy: down memory lane.

PMID- 8562361
TI  - Politics: the gospel truth.

PMID- 8562362
TI  - Social anthropology: conference characters.

PMID- 8562363
TI  - Ethnic minority health. Fair provision.

PMID- 8562365
TI  - Ethnic minority health. Equal access. Interview by Christina Potrykus.

PMID- 8562364
TI  - Ethnic minority health. Help yourself.

PMID- 8562366
TI  - The great quest for leadership.

PMID- 8562368
TI  - Leadership: the hidden dangers.

PMID- 8562367
TI  - A programme for nursing leadership.

PMID- 8562369
TI  - [Requirements in ambulatory surgery at a pediatric surgical university
      department].

PMID- 8562370
TI  - [Sedation and analgesia in neonatology. 2. Analgesics].

PMID- 8562371
TI  - [Does the bathing of newborns enhance the risk of umbilical infections?].

PMID- 8562372
TI  - [Nursing report on an extremely immature premature infant with respiratory
      distress syndrome].

PMID- 8562373
TI  - [The little bear--a picture story on nursing and treatment measures in
      hemophilia].

PMID- 8562374
TI  - [Environmental protection as a part of hygiene and health promotion].

PMID- 8562375
TI  - [Poisonous and less poisonous plants. 20].

PMID- 8562376
TI  - [Permanent pacifiers? no--thank you. The use and misuse of pacifiers and possible
      consequences].

PMID- 8562377
TI  - [30 years of experience in pediatric nursing in the post war area].

PMID- 8562378
TI  - [Tuberculosis].

PMID- 8562379
TI  - Interleukin 2 in the management of acute leukaemia.

PMID- 8562380
TI  - The use of IgH fingerprinting and ASO-dependent PCR for the investigation of
      residual disease (MRD) in ALL.
AB  - In acute lymphoblastic leukaemia (ALL), investigation of minimal residual disease
      by conventional morphology and immunology fails to detect levels of residual
      disease of < 1 leukaemic in 10-100 normal cells. The use of polymerase chain
      reaction (PCR) to exploit the diversity of the complementarity determining region
      (CDR) and immunoglobulin variable heavy chain (VH) family specific usage has
      greatly improved the sensitivity up to one leukaemic cell in 10(5)-10(6) normal
      bone marrow cells. Here we report on a prospective study of 14 patients with ALL
      of B-cell lineage by using a combined PCR approach which estimates levels of
      disease between 1:10(3) and 1:10(5). The sequential use of allele-specific
      oligoprimer (ASO) independent tests (using framework 1. FR1 and 3, FR3 primers
      with a JH consensus primer, sensitivity up to 1:5 x 10(3)) and ASO-dependent PCR
      (sensitivity up to 1:10(5)) assays were applied to 64 bone marrow (BM) follow-up
      samples in a sequential array of tests. Results presented in this study indicate
      high concordance of MRD among different tests for samples with level of residual
      disease > 1:5 x 10(3). Consequently, samples positive by the FR1 and FR3
      fingerprinting tests were confirmed by the more sensitive ASO-dependent tests, as
      expected. However, the ASO-dependent assays revealed levels of disease undetected
      by the FR1 and FR3 test. Although a higher level of sensitivity is provided by
      the ASO-dependent tests, the FR1 and FR3 fingerprinting tests allow MRD
      investigation in patients with oligoclonal B cell proliferations, CDR3 region of
      size < 15 bp or with ASO primers unsuitable for PCR investigation on technical
      grounds (i.e. background signal). If a sequential order of investigation from
      less (e.g. FR1 and FR3 fingerprinting) to more sensitive tests (ASO-dependent) is
      applied, an indirect estimate of MRD is obtained for patients with level of
      disease < 1:10(3).

PMID- 8562381
TI  - Expression and role in growth regulation of tumour necrosis factor receptors p55
      and p75 in acute myeloblastic leukaemia cells.
AB  - Tumour necrosis factor (TNF)-alpha exerts multiple effects on human acute
      myeloblastic leukaemia (AML) cells in vitro, including (1) synergistic
      stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage
      colony-stimulating factor (GM-CSF); (2) inhibition of granulocyte-CSF (G-CSF) and
      stem cell factor (SCF)-induced growth; (3) suppression of multiplication of
      clonogenic leukaemic cells; (4) induction of autocrine growth. Recently, two
      distinct TNF receptors (TNF-Rs), TNF-Rp55 and TNF-Rp75, have been identified. In
      this study we show that both receptors are expressed on freshly isolated AML
      blasts, with p75 being the predominant TNF-receptor type. This study investigates
      the roles of these two receptors in TNF-alpha-driven growth regulation of AML
      blasts in vitro. Using a receptor-specific antibody, it is shown that both
      receptor types participate in TNF-alpha-mediated stimulation of GM-CSF/IL-3
      induced proliferation and in TNF-alpha-induced autocrine growth. In contrast, the
      TNF-alpha-triggered growth inhibition (antiproliferation) and the potent
      suppression of G-CSF- and SCF-induced proliferation exclusively result from
      activation of TNF-Rp55. Taken together, these results suggest that the
      proliferative effects of TNF-alpha on AML blasts are mediated through both p55
      and p75 TNF receptors, whereas the TNF-alpha-signalled growth inhibition is
      exclusively transduced via TNF-Rp55.

PMID- 8562382
TI  - The human CD40 gene lies within chromosome 20q deletions associated with myeloid
      malignancies.
AB  - Deletions of chromosome 20q are associated with myeloid malignancies and have
      been previously shown to arise in a multipotent progenitor of both myeloid and B
      cells. However, B-cell differentiation from the abnormal progenitor was impaired.
      The CD40 antigen is a surface glycoprotein which is expressed in B cells and
      haemopoietic stem cells and is important for B-cell growth and development.
      Following the recent mapping of CD40 to chromosome 20q we sought to determine its
      position relative to 20q deletions. Analysis of lymphoblastoid cell lines
      carrying 20q deletions placed CD40 within a 19-21 cM interval which is almost
      coincidental with the common deleted region defined by previous analysis of
      patient samples. Our results raise the possibility that genetic alteration of
      this locus may contribute to the pathogenesis of myeloid disorders associated
      with 20q deletions.

PMID- 8562383
TI  - Molecular evidence for a common leukaemic progenitor in acute mixed lymphoid and
      myeloid leukaemia.
AB  - De novo acute leukaemia presenting with a mixed lymphoid and myeloid leukaemic
      population has rarely been described. We have used the consensus Ig heavy chain
      primers and DNA isolated from these two distinct populations of cells in
      polymerase chain reactions. We demonstrated that both populations of cells
      exhibited Ig heavy chain gene rearrangements. Cloning and subsequent DNA
      sequencing of the amplified products showed a common V-D-J junctional nucleotide
      sequence. This work therefore provides the first evidence that the leukaemic
      cells in de novo acute leukaemia with a mixed lymphoid and myeloid population are
      derived from a common progenitor clone and may offer an explanation for the poor
      prognosis in these patients.

PMID- 8562384
TI  - Multiple gastric involvement by myeloid antigen CD13-positive non-secretory
      plasma cell leukaemia.
AB  - Gastrointestinal tract involvement is a rare complication of plasma cell
      neoplasia. We present a case of non-secretory type primary plasma cell leukaemia
      (PCL) with multiple gastric involvement. Dual surface antigen analysis of bone
      marrow cells revealed that atypical plasma cells coexpressed CD38 and myeloid
      antigen CD13. Upper gastrointestinal endoscopy disclosed multiple submucosal
      masses in the body of the stomach. Endoscopic biopsy specimens showed marked
      infiltration of atypical plasma cells consistent with a diagnosis of gastric
      involvement by PCL. Since CD13 antigen is identical to aminopeptidase N, a
      membrane-bound glycoprotein thought to be involved in the process of tumour
      invasion, CD13 expression on neoplastic plasma cells may be related to the
      gastric involvement in this patient.

PMID- 8562385
TI  - A case of ovarian carcinoma with production of granulocyte colony-stimulating
      factor.
AB  - A 60-year-old female with ovarian carcinoma showed marked leucocytosis. After
      exploratory laparotomy she had received carboplatin-based chemotherapy, but she
      died of respiratory failure. In this case the immunohistochemical examination of
      the tumour cells showed partial-positive staining for anti-G-CSF monoclonal
      antibody in addition to the elevation of the serum G-CSF concentration. This case
      is the first report of an ovarian carcinoma producing G-CSF.

PMID- 8562386
TI  - Glass slide smears are a suitable source for RT-PCR-based analysis of chromosomal
      aberrations in leukaemias.
AB  - The polymerase chain reaction (PCR) is a well-established method to detect
      cytogenetic abnormalities. The handling of fresh specimens is difficult,
      therefore a method to use smears of blood or bone marrow as a source would be
      advantageous. Furthermore, such a technique would give the opportunity to
      investigate retrospectively bone marrow smears in leukaemias without cytogenetic
      results. The aim of the present study was to investigate the influence of
      staining procedures and laboratory handling of smears. We chose CML cases as a
      model. We demonstrated that smears are a suitable source for PCR without loss of
      information caused by previous routine laboratory handling.

PMID- 8562387
TI  - Determinants of haemoglobin level in steady-state homozygous sickle cell disease.
AB  - High total haemoglobin levels in homozygous sickle cell (SS) disease are a risk
      factor for painful crises, avascular necrosis of the femoral head, proliferative
      sickle retinopathy, and the acute chest syndrome. Since lowering the haemoglobin
      level may ameliorate these features, understanding the determinants of total
      haemoglobin may be of practical importance. A range of possible determinants
      including red cell characteristics, reticulocytes, serum iron, transferrin
      saturation, serum ferritin, alpha thalassaemia status, red cell mass and plasma
      volume, oxygen affinity, red cell survival, transferrin receptor and
      erythropoietin levels have been measured in 62 patients selected to provide a
      range of total haemoglobin and fetal haemoglobin levels. There were weak negative
      associations of haemoglobin with mean cell volume and mean cell haemoglobin
      concentration, strong negative associations with proportional reticulocyte
      counts, oxygen affinity, plasma volume, serum transferrin receptors, and
      erythropoietin levels and strong positive associations with red cell mass.
      Weighted analysis suggested that the statistically independent determinants of
      haemoglobin level were alpha thalassaemia, sex, red cell mass/body weight, plasma
      volume/body weight, fetal haemoglobin, and red cell count. The apparent
      contributions of red cell survival, P50, reticulocyte count, serum transferrin
      receptor and erythropoietin levels were explained by the effects of these other
      variables. The independent determinants as a group explained 91% of the variation
      in haemoglobin level.

PMID- 8562388
TI  - Erythropoietin production and erythropoiesis in compensated and anaemic states of
      hereditary spherocytosis.
AB  - A compensated haemolytic state is defined by decreased red cell life-span without
      anaemia, i.e. by increased erythropoiesis in the absence of the physiological
      stimulus for erythropoietin (Epo) production. We evaluated s-Epo levels and the
      expansion of erythropoiesis (as measured by circulating transferrin receptor, s
      TfR) in 32 patients with hereditary spherocytosis (HS) with the aim of verifying
      whether the enhanced erythropoiesis of compensated haemolysis was Epo-dependent.
      20 of the patients (62.5%) had normal Hb values (> 12 g/dl in females and > 13
      g/dl in males). Their compensated haemolytic state was the result of up to 8.2
      times normal s-Epo and up to 3.9 times normal s-TfR levels, which were maintained
      by physiological regulation of erythropoiesis, as documented by the inverse
      dependence of Hb on s-Epo levels. Considering that patients with iron-deficiency
      anaemia represented the predicted physiological Epo response to anaemia, the
      observed/predicted in s-Epo ratio (O/P ratio) was calculated in HS patients with
      anaemia and was used as an index of the adequateness of Epo production. All the
      anaemic HS patients had an O/P ratio > 1, documenting inappropriately high s-Epo
      levels. This work demonstrates that the compensated haemolytic state of HS
      patients is produced by an inappropriately high s-Epo level, and that the pattern
      of Epo overproduction is a biological characteristic of the disease.

PMID- 8562389
TI  - Response to immunosuppressive therapy and an HLA-DRB1 allele in patients with
      aplastic anaemia: HLA-DRB1*1501 does not predict response to antithymocyte
      globulin.
AB  - HLA-DRB1*1501, a subtype of HLA-DR2, has been shown to be closely associated with
      a good response to cyclosporine (CyA) therapy in patients with aplastic anaemia
      (AA). To determine whether this DRB1 allele can also predict a response to
      antithymocyte globulin (ATG) therapy in AA patients, we analysed the results of
      HLA-DRB1 typing in 59 Japanese patients who received ATG within 2 years after
      diagnosis of AA and also in 52 patients treated with CyA. All patients were
      divided into three groups: those with DRB1*1501, those with DRB1*1502, and those
      without either of these two alleles (DR2-). The response rate to ATG in
      DRB1*1501+ patients (56%) was not significantly higher than that in DRB1*1502+
      patients (47%) and in the other DR2- patients (54%). In contrast, the response
      rate to CyA therapy in DRB1*1501+ patients (92%) was significantly higher than
      that in the DRB1*1502+ (41%) and in DR2- patients (57%). Multivariate analysis
      revealed that possessing DRB1*1501 was an independent factor significantly
      predictive of a good response to CyA. These results indicate that although
      identifying the DRB1*1501 allele in AA patients prior to therapy is predictive of
      a good response to CyA therapy, it does not have a predictive value for ATG
      therapy.

PMID- 8562390
TI  - Glyburide-induced acute haemolysis in a G6PD-deficient patient with NIDDM.
AB  - In a 61-year-old man with glucose-6-phosphate dehydrogenase (G6PD) deficiency and
      poorly controlled non-insulin-dependent diabetes mellitus, an episode of acute
      haemolysis occurred after the administration of glyburide (glibenclamide).
      Erythrocyte fragmentation, with haemoglobin condensation zones next to clear
      zones, was observed on peripheral blood smears. Since autoimmune haemolysis was
      excluded on the basis of laboratory data, acute haemolysis was ascribed to G6PD
      deficiency.

PMID- 8562391
TI  - Motility of rhG-CSF-induced neutrophils in patients undergoing chemotherapy:
      evidence for inhibition detected by image analysis.
AB  - The motility of circulating neutrophils from seven patients affected by
      intermediate and high-grade non-Hodgkin's lymphoma was investigated before and
      after rhG-CSF administration (5 micrograms/kg/d for 5 d subcutaneously) in the
      course of chemotherapy. Random motility and bacterial lipopolysaccharide-induced
      chemotaxis were studied by the micropore filter technique in a Boyden chamber.
      These functions were evaluated by a very sensitive technique, based on a computer
      assisted image processing system, capable of giving several parameters about the
      kinetics of cell migration. Along with a significant increase in neutrophil
      number, a significant decrease both in random and stimulated motility was found.
      The kinetics of cell migration showed that the cells maintained the typical
      gaussian pattern of random motility. On the contrary, neutrophils were found to
      have lost the typical stimulated migration peak. These findings are consistent
      with a rhG-CSF-induced impairment of the directional movement, rather than of the
      ability of moving at random. These effects were found in patients who, in the
      same experimental conditions, had displayed an enhanced phagocytosis and
      phagocytosis-associated chemiluminescence along with an enhanced CD32 expression,
      not due to an aspecific cell manipulation. Two hypotheses may be taken into
      account: (i) an increased adhesiveness due to a direct or an indirect activity of
      the cytokine; (ii) an abnormality in the cytoskeleton maturation and/or
      rearrangement during the accelerated bone marrow transit of myeloid cells. These
      findings emphasize that rh-GCSF administration can modulate several functions
      which play an important role in host defence, and suggest the utility of carrying
      out further studies to investigate the optimum dosage both to correct neutrophil
      number and preserve neutrophil functional activities.

PMID- 8562392
TI  - Sodium butyrate delays neutrophil apoptosis: role of protein biosynthesis in
      neutrophil survival.
AB  - Sodium butyrate, which directly affects chromatin structure and function in many
      cells, is as effective as granulocyte-macrophage colony-stimulating factor (GM
      CSF) in delaying apoptosis in human neutrophils. Both butyrate and GM-CSF
      preserved the ability of neutrophils cultured for 22 h in vitro to generate
      reactive oxidants and express receptors such as CD16. They also delayed apoptotic
      morphology and DNA fragmentation, and stimulated de novo biosynthesis: newly
      labelled polypeptides detected by 2D-polyacrylamide gel electrophoresis after
      treatment with GM-CSF and butyrate were very similar. Cycloheximide abrogated the
      effects of both GM-CSF and butyrate. Exposure to butyrate for 1 h did not prime
      oxidant production and did not up-regulate expression of CD11b. Hence, unlike GM
      CSF, butyrate does not stimulate translocation of granules to the plasma
      membrane. These data suggest that active gene expression is involved in the
      regulation of neutrophil apoptosis and changes in chromatin structure and
      function may control apopotosis in these cells.

PMID- 8562393
TI  - Further evidence for the clonal nature of the idiopathic hypereosinophilic
      syndrome: complete haematological and cytogenetic remission induced by interferon
      alpha in a case with a unique chromosomal abnormality.
AB  - A 49-year-old man with the idiopathic hypereosinophilic syndrome (HES) and a
      unique chromosomal abnormality 46,XY,t(5;9)(q32;q33) is reported. Complete
      cytogenetic remission was induced by interferon alpha-2b (IFN-alpha). The
      beneficial action of IFN-alpha in different stem-cell disorders such as CML, HES,
      multiple myeloma and solid tumours such as hypernephroma or malignant melanoma
      suggests a common regulatory effect possibly by immunomodulation or other (immune
      mediated) mechanisms, but the exact pathophysiological mechanisms remain
      hypothetic and unresolved. Since it has been known for some years that the genes
      encoding for GM-CSF, IL-3 and IL-5 reside on the long arm of chromosome 5, it
      could be possible that the chromosomal translocation in our patient resulted in
      excess production of these cytokines, hence causing the hypereosinophilia. This
      case report and the results obtained from the literature review support the
      growing body of evidence that IFN-alpha has a major place in the long-term
      treatment of HES, especially in those cases resistant to conventional treatment,
      with cytogenetic abnormalities, or presenting as a myeloproliferative variant of
      HES. In those cases IFN-alpha results in lower morbidity, lower mortality and
      long-term survival.

PMID- 8562394
TI  - Identification of early plasma cells in peripheral blood and their clinical
      significance.
AB  - In the peripheral blood (PB) we detected so-called early plasma cells that might
      already be committed to entering the bone marrow (BM). By two-colour staining
      with FITC-anti-CD38 antibody, their intensity (CD38++) of expression of CD38
      antigen was between that of germinal centre (GC) B cells (low expression (CD38+))
      and that of BM plasma cells (high expression (CD38++)), and their phenotype was
      CD38++ CD19+ CD10- CD20- CD21+ CD24- CD39+ CD5- VLA-4+ VLA-5- MPC-1- without
      expression of surface membrane IgM (SmIgM). Morphological and immunological
      examination of the sorted cells confirmed that they were plasmacytoid cells with
      expression of cytoplasmic IgG (cIgG). Variations of these early plasma cells were
      examined in various diseases. In active systemic lupus erythematosus, bacterial
      septicaemia and liver cirrhosis, early plasma cell levels were significantly
      increased in PB, and after subsidence of such inflammation (inactive states)
      these cells returned to normal levels. In contrast, normal early plasma cells
      were significantly suppressed in myelomas, whilst normal or slightly increased
      numbers of early plasma cells was found in benign monoclonal gammopathy (BMG). In
      addition, the number of normal early plasma cells returned to a normal level in
      myeloma cases with complete responses. Therefore, early plasma cells were
      identified phenotypically, and an increase and decrease in these cells in PB may
      reflect mobilization and suppression, respectively, of activated B cells into BM
      plasma cells.

PMID- 8562395
TI  - Prolonged E-selectin induction by monocytes potentiates the adhesion of flowing
      neutrophils to cultured endothelial cells.
AB  - We investigated the hypothesis that the infiltration of monocytes into inflamed
      tissue or damaged vessels would induce a secondary accumulation of neutrophils.
      Confluent human umbilical vein endothelial cells (HUVEC) and blood monocytes (0.5
      or 0.05 monocytes/endothelial cell) were co-incubated for 4 or 24 h. The adhesion
      of neutrophils flowing over HUVEC was then analysed by video microscopy. Co
      incubation caused up to a 40-fold increase in neutrophil adhesion, dependent upon
      monocyte/HUVEC ratio and duration of incubation. At the lower monocyte/HUVEC
      ratio, rolling adhesion alone was induced after 4 h co-incubation; however, the
      full repertoire of rolling, immobilization and migration of neutrophils was
      observed at all other combinations of co-culture ratio and exposure time. After
      maximal stimulation by monocytes, antibody blockade of the neutrophil integrin
      CD18 inhibited neutrophil arrest and migration and revealed underlying rolling
      adhesion. Rolling was supported by endothelial E-selectin as demonstrated by the
      almost total abolition of adhesion by a blocking antibody. In a direct
      comparison, monocytes, tumour necrosis factor alpha (TNF-alpha) and interleukin-1
      beta (IL-1 beta) were assessed for their ability to induce endothelial expression
      of E-selectin. E selectin was significantly increased by all agents at 4 h, but
      monocytes alone were able to maintain high levels of E-selectin expression for 24
      h. We conclude that monocytes can induce prolonged neutrophil adhesion and
      migration by activating endothelial cells and causing expression of E-selectin.

PMID- 8562396
TI  - The thromboxane mimetic, U-46619, induces the aggregation of fish thrombocytes.
AB  - Fish blood contains nucleated cells termed thrombocytes which are thought to be
      functionally analogous to mammalian platelets. The present study was undertaken
      to assess the aggregatory response of peripheral blood thrombocytes from the
      rainbow trout, Oncorhynchus mykiss. Incubation of Percoll density gradient
      purified thrombocytes with the thromboxane A2 mimetic, U-46619 (0.03-10 microM),
      alone or in the presence of human or trout fibrinogen, elicited a dose-dependent
      aggregatory response. A greater amount of aggregation was observed in the
      presence of fish, rather than human, fibrinogen (e.g. c 55% compared with 15%
      maximal aggregation respectively). This response was inhibited by pre-incubation
      of thrombocytes with the specific thromboxane A2 receptor antagonist, GR32191
      (0.01-10 microM) with an IC50 value of 5.7 microM. Ultrastructural and
      aggregometry studies of thrombocyte aggregation at various time periods (1-12
      min) after incubation with U-46619 (0.5 microM) revealed clear differences
      between the amount and dynamics of thrombocyte clumping in the presence of human,
      compared with trout, fibrinogen (final concentration 400 micrograms ml-1).
      Thrombocytes rapidly underwent shape change and aggregation after only 1 min
      incubation without the initial involvement of any other cell types. The maximum
      degree of aggregation was achieved after 4-8 min with larger aggregates formed in
      the presence of trout compared than human fibrinogen. Ultrastructurally, the
      thrombocytes in these aggregates displayed a number of changes compared with non
      stimulated cells, including increased pseudopodial activity, a more pronounced
      canalicular system and condensation of the nuclear heterochromatin. After 12 min
      incubation the clumps of thrombocytes showed progressive disaggregatory
      behaviour, with some cells reverting back to their normal in vivo appearance.
      Neutrophilic granulocytes, present as contaminants in the thrombocyte
      suspensions, were occasionally found attached to the thrombocyte aggregates,
      perhaps suggesting a specific interaction similar to that occurring in mammals.
      Finally, and also of some significance, was the finding that trout thrombocytes
      exhibit phagocytic activity in vitro towards cell debris and contaminating
      bacteria, indicating that this cell type may possess both haemostatic and
      immunological capacities.

PMID- 8562397
TI  - Bleeding disorder due to platelet prostaglandin H synthase-1 (PGHS-1) deficiency.
AB  - Defective platelet prostaglandin H synthase (PGHS) activity has been recognized
      as a cause of bleeding disorders, but the defect has not been characterized. We
      evaluated three female patients aged 37, 48 and 55 who presented with a mild
      bleeding disorder due to platelet dysfunction. None of the patients had
      underlying diseases or reported use of aspirin or other nonsteroidal anti
      inflammatory drugs. Coagulation screening tests and platelet count were normal in
      each patient. Platelet aggregation in response to adenosine diphosphate (ADP),
      collagen and epinephrine were subnormal, characterized by an abnormal second-wave
      aggregation and propensity for disaggregation. Arachidonate-induced platelet
      aggregation was defective, whereas PGH2-induced aggregation was normal. Platelet
      thromboxane A2 (TXA2) production in response to arachidonic acid was reduced in
      all three patients, i.e. 11.7, 4.6 and 4.4 ng TXB2/3 x 10(8) plt respectively
      (normal range was 49-81 ng/3 x 10(8) plt), whereas they were normal in response
      to exogenous PGH2, i.e. 71.4, 56.6 and 48.9 ng/3 x 10(8) respectively (normal
      range 49-85 ng/3 x 10(8) plt). These results are consistent with a deficiency of
      platelet PGHS activity. The level of the constitutive platelet PGHS-1 and TXA2
      synthase (TXAS) proteins were determined on platelet microsomal fractions by
      Western blot analysis using affinity-purified polyclonal antibodies highly
      specific for human PGHS-1 and TXAS, respectively. In two patients the 70 kD PGHS
      1 protein was undetectable, whereas it was normal in the third patient. The 60 kD
      TXAS band was normal in all three patients. These findings indicate that human
      platelet PGHS-1 deficiency is due to two types of enzyme defects: type 1 defect
      is manifested by an undetectable PGHS-1 protein in platelets whereas the type 2
      defect is manifested by a normal quantity of PGHS-1 protein which has an impaired
      catalytic activity.

PMID- 8562398
TI  - Cytomegalovirus-induced thrombocytopenia and haemolysis in an immunocompetent
      adult.
AB  - We describe a patient with severe symptomatic thrombocytopenia and haemolytic
      anaemia caused by cytomegalovirus (CMV) infection. As far as we know, this is the
      second case in the literature. Treatment with ganciclovir seemed to be more
      effective for thrombocytopenia than treatment with corticosteroids. The
      hypothetical mechanisms leading to thrombocytopenia and haemolysis in CMV
      infection are briefly discussed. In cases of acute thrombocytopenia and clinical
      manifestations of an infectious disease, with or without haemolysis, testing for
      CMV may be useful in connection with therapeutic consequences.

PMID- 8562399
TI  - A whole blood assay for platelet HPA1 (PLA1) phenotyping applicable to large
      scale screening.
AB  - Any future programme of antenatal screening of pregnancies for risk of neonatal
      alloimmune thrombocytopenia will have as a major requirement the availability of
      cost-effective assays which can be applied to large numbers of samples. To
      address this, we developed a competitive ELISA to type whole blood samples for
      the platelet alloantigen HPA1a, based on the use of purified glycoprotein (GP)
      IIb/IIIa from donors of known HPA1 genotype along with well characterized anti
      HPA1a antiserum. Microtitre plates were coated with purified GPIIb/IIIa from
      donors of genotype HPA1a1a/3a3a. Anticoagulated whole blood of unknown HPA1 type
      was added to each well followed by anti-HPA1a. Residual antiHPA1a antibody not
      bound to the platelets in the test blood sample, bound to the immobilized HPA1a
      on the plate and was quantitated by standard ELISA. 475 blood donors were typed
      by the assay and the results compared in a blinded comparison with typing in the
      Capture-Ptm assay. Concordance was 100% (468 HPA1a positive and seven HPA1a
      negative). The HPA1 type of control samples stored as whole blood could be
      discriminated by this assay for up to 23 d of storage at 4 degrees C. This assay
      should be suitable for use in large-scale population screening programmes.

PMID- 8562400
TI  - Haemostatic and rheological factors in intermittent claudication: the influence
      of smoking and extent of arterial disease.
AB  - Patients with intermittent claudication have been reported to have disturbances
      in blood rheology and haemostasis. Whether these disturbances are a result of, or
      largely independent of, smoking history and arterial narrowing has not yet been
      established. The levels of whole blood and plasma viscosity, haematocrit, von
      Willebrand factor antigen, fibrin D-dimer antigen and urinary fibrinopeptide A
      antigen were compared in 617 claudicants and 722 controls from two
      epidemiological studies in Edinburgh. After adjustment for age and sex, all
      factors, except whole blood viscosity and haematocrit, were significantly higher
      in the claudicants compared to controls (P < or = 0.001). The risk of
      intermittent claudication was significantly raised for unit change in each
      factor, except for whole blood viscosity and haematocrit. Adjustment for lifetime
      smoking had little effect on the odds ratios. After further adjustment for the
      ankle brachial pressure index (as a measure of the extent of peripheral arterial
      disease), haematocrit, von Willebrand factor and urinary fibrinopeptide A showed
      a significant independent relationship with the risk of intermittent
      claudication. We conclude that the association between selected rheological and
      haemostatic factors and leg ischaemia is largely independent of both smoking
      history and the extent of arterial narrowing, and may be directly related to
      microvascular ischaemia.

PMID- 8562401
TI  - Growth of macroscopic human megakaryocyte colonies from cord blood in culture
      with recombinant human thrombopoietin (c-mpl ligand) and the effects of
      gestational age on frequency of colonies.
AB  - We investigated the effects of recombinant human thrombopoietin (rhTPO) on the
      growth of megakaryocytic (MK) colony derived MK progenitors from human cord blood
      (CB) in vitro and the effects of gestational age on the number of MK colonies.
      The results demonstrated that rhTPO alone supports the growth of MK colonies and
      induces not only proliferation but also differentiation of MK progenitors. CB
      shows a high frequency of MK colonies; most of which are very large and
      equivalent to high proliferative potential colony-forming unit-megakaryocyte. The
      colonies could be macroscopically observed as white spots in the culture dish.
      Preterm neonates showed greater numbers of MK progenitors than term neonates and
      there was an inverse correlation between gestational age and concentration of MK
      progenitors of CB. The effects of gestational age was an important factor on the
      proliferative capacity of MK progenitors and on the response to rhTPO.

PMID- 8562402
TI  - Transcriptional regulation of the human factor IX promoter by the orphan receptor
      superfamily factor, HNF4, ARP1 and COUP/Ear3.
AB  - A study of the human clotting factor IX promoter by DNase I footprinting and gel
      shifts in vitro, and by functional analysis of HepG2 cells in vivo, suggests that
      the liver-enriched transcription factor, HNF4, is involved in transactivating two
      cis-acting elements, i.e. X (nucleotides -15 to +3) and Y (nucleotides +15 to
      +36), in addition to the well-known element centred around nucleotide -20. Other
      members of the orphan receptor superfamily, e.g. ARP1 and COUP/Ear3, repress the
      factor IX promoter possibly by competition with HNF4 binding sites in the X and Y
      elements, but probably not at the -20 element. Mutations at -6 in the promoter,
      similar to those found in patients with haemophilia B, hinder HNF4 binding and
      transactivation of the X element, suggesting that impaired HNF4 binding
      contributes to the down-regulation of the factor IX expression in these patients,
      but is unlikely to be the only factor involved.

PMID- 8562403
TI  - A novel mutation (Leu817Pro) causing type 2A von Willebrand disease.
AB  - We studied a patient affected by von Willebrand disease type 2A who experienced
      several mild bleeding episodes and was characterized by markedly reduced
      haemostatic parameters. In the exon 28 of von Willebrand factor (vWF) gene a T to
      C transition at nucleotide 8680, resulting in the missense mutation Leu817Pro,
      was found in the heterozygous form in the patient and in two affected relatives.
      As suggested by the presence in platelets of a complete spectrum of vWF multimers
      as well as by the increased vWF antigen levels and improved haemostasis after
      DDAVP treatment, the mutation is compatible with normal multimerization, and
      could be responsible for a reduced stability or an impaired physiological
      secretion of vWF.

PMID- 8562404
TI  - Activated protein C sensitivity ratio in pregnant women at delivery.
AB  - We studied activated protein C sensitivity ratio (APC-SR), factors V and VIII
      activity and von Willebrand antigen in control women, women using oral
      contraceptives, and pregnant women at delivery. The mean APC-SR of 2.4 in
      pregnant women was significantly lower than the mean APC-SR value of 3.5 for both
      the other groups and 45% of pregnant women had a ratio below the 5th percentile
      of the control group. None of them carried the R506-->Q mutation. This decreased
      ratio at delivery appeared to be connected, at least in part, with increased VIII
      activity. Thus, APC-SR at delivery should not be used to detect APC resistance.

PMID- 8562405
TI  - Time for a new acute myeloid leukaemia classification?

PMID- 8562406
TI  - MDS and acute monocytic leukaemia after retinoblastoma.

PMID- 8562407
TI  - Carboxy-terminal peptides (C1-24 and C13-24 but not C1-13) of platelet factor 4
      inhibit murine megakaryocytopoiesis, an activity which is neutralized by heparin.
AB  - Negative regulation of megakaryocytopoiesis is a complex process involving
      various cytokines. One of these cytokines is platelet factor 4 (PF4), a
      megakaryocyte/platelet specific protein. PF4 and a carboxy-terminal peptide
      related to PF4 have been reported to inhibit human and murine
      megakaryocytopoiesis. The growth of several megakaryoblastic cell lines: human
      erythroleukaemia cell line (HEL). Meg-01 and Dami, was also inhibited by PF4 and
      a 13-24 carboxy-terminal peptide related to PF4. We report that peptides
      corresponding to the 1-24 and 13-24 but not 1-13 carboxy-terminal region of PF4
      inhibit murine megakaryocytopoiesis both in vivo (5 micrograms/inj) and in vitro
      (2.5 and 5 micrograms/ml). Moreover, such an inhibitory activity of PF4-related
      peptides is abrogated by heparin (5 IU/dish). These overall data indicate that
      carboxy-terminal PF4-related peptides retain the inhibitory effect of PF4 on both
      murine single MK and CFU-MK in vivo and in vitro by acting on an early stage of
      megakaryocytopoiesis and strongly suggest that the inhibitory activity of the
      multi-functional PF4 might be localized in a short carboxy-terminal region which
      might include, in part, the PF4 heparin binding domain.

PMID- 8562408
TI  - Indications for haemopoietic precursor cell transplants in Europe. European Group
      for Blood and Marrow Transplantation (EBMT).
AB  - Information on 17,206 haemopoietic precursor cell transplants performed in 12
      European countries between 1991 and 1993 was used to assess the number of
      transplants per million inhabitants per year by principal indication and donor
      source. 16.6 transplants were performed per million inhabitants per year with a
      range of 9.4-27.7. Differences between countries may be due to the availability
      of beds and resources or to divergent opinions about treatments. We used the
      coefficient of variation (CV) to assess the degree of agreement between
      clinicians with regard to different procedures and indications, with a cut-off of
      < or = 45% to indicate consensus. The rate of allogeneic transplantation between
      the 12 countries was more 'homogenous' than that of autologous transplantation
      (mean 6.8 per million inhabitants, range 5.2-9.5, CV 20% versus mean 9.8 per
      million inhabitants, range 3.6-18.4, CV 40%). Consensus was found for
      allografting in chronic myeloid leukaemia (CML) in first chronic phase (CV 19%),
      CML in later phases (CV 31%), acute myeloid leukaemia (AML) in first complete
      remission (CV 41%), AML beyond first complete remission (CV 34%), acute
      lymphoblastic leukaemia beyond first complete remission (23%), and severe
      aplastic anaemia (29%). Consensus for autografting was observed for Hodgkin's
      disease (CV 44%), non-Hodgkin's lymphoma (CV 44%), and AML beyond first remission
      (CV 41%). With this method an assessment of medical opinion can be made in spite
      of the different availabilities of resources. These data reflect the state of the
      art in haemopoietic precursor cell usage in Europe; they provide a basis for
      patient counselling and health-care planning.

PMID- 8562409
TI  - Intermediate-dose melphalan (IDM) combined with G-CSF (filgrastim) is an
      effective and safe induction therapy for autologous stem cell transplantation in
      multiple myeloma.
AB  - Twenty-one previously untreated multiple myeloma (MM) patients and 10 previously
      treated patients with refractory or relapsed disease received two or three cycles
      of intermediate-dose melphalan (70 mg/m2) (IDM), administered intravenously every
      6 weeks. Seven previously untreated patients received three and all other
      patients received two courses of IDM. The objective of the study was to reduce
      the toxicity of high-dose melphalan (140 mg/m2) (HDM) while maintaining its
      cytotoxic efficacy and secondly to ensure the possibility of collecting
      sufficient numbers of peripheral blood stem cells (PBSC) for transplantation. 18
      (85%) previously untreated patients responded, of whom four achieved CR (18%). In
      addition five out of 10 previously treated patients with refractory or relapsed
      disease responded although bone marrow toxicity in this category was a major
      drawback. Toxicity was moderate, consisting of alopecia and moderate bone marrow
      suppression: the granulocyte count dropped below 0.5 x 10(9)/l and platelets
      below 25 x 10(9)/l for a median of 8 and 6 d, respectively. No serious infections
      occurred and the majority of patients attended the out-patient clinic. In 12/14
      previously untreated patients sufficient peripheral blood CD34+ cells for harvest
      were present in the repopulation phase after the first IDM. In nine patients
      peripheral blood stem cells were collected and eight patients have undergone
      successful transplantation. Repeated IDM followed by filgrastim is highly
      effective in untreated MM and may be safely administered to reduce tumour load
      prior to PBSC collection. Autologous stem cells harvested after repeated IDM have
      a full long-term repopulating capacity.

PMID- 8562410
TI  - Role of allogeneic bone marrow transplantation from an HLA-identical sibling or a
      matched unrelated donor in the treatment of children with juvenile chronic
      myeloid leukaemia.
AB  - Seven children (age range 1.8-11 years) with juvenile chronic myelomonocytic
      leukaemia (JCML) received an allogeneic bone marrow transplantation (BMT), four
      from an HLA-identical sibling and three from a matched unrelated donor. In the
      four children transplanted using an HLA-identical sibling, conditioning regimen
      included busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM), whereas
      graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine-A (Cs-A).
      The preparative regimen was well tolerated and all patients engrafted promptly.
      None of the patients have relapsed and all four children remain in haematological
      remission after an observation time of 7, 24, 25 and 48 months, respectively. Of
      the three children given BMT from an unrelated volunteer, one was < 2 years of
      age and she received the BU/CY/L-PAM regimen. In view of the increased risk of
      graft rejection described in patients transplanted from unrelated donors, we
      chose to prepare the other two patients with fractionated total body irradiation
      (TBI), thiotepa and CY. Cs-A, short-term methotrexate and Campath-1G in vivo were
      employed to prevent GVHD in this group of patients. Graft failure with autologous
      reconstitution of haemopoiesis occurred in the child given the chemotherapy-based
      regimen. One of the two girls given TBI relapsed after BMT; therefore only one of
      the three patients who received a marrow transplant from a matched unrelated
      donor survives in complete haematological remission 10 months after BMT. Our
      study suggests that the conditioning regimen we employed for allogeneic BMT from
      a compatible sibling is an effective means of eradicating the leukaemic clone. In
      our experience, results obtained using unrelated donors are less satisfactory
      and, at present, the use of such donors seems to be riskier and associated with a
      lower success rate as compared with BMT from an HLA-identical sibling.

PMID- 8562411
TI  - Efficacy of recombinant interferon-alpha (rIFN-alpha) in polycythaemia vera: a
      study of 17 patients and an analysis of published data.
AB  - The efficacy and tolerability of rIFN-alpha has been evaluated in 17 selected
      patients with symptomatic polycythaemia vera, diagnosed according to the PRV
      Study Group criteria. Complete disease control (CR) was achieved, after 1-12
      months, in nine patients, with partial control in a further five cases. Three
      patients failed to respond. Pruritus significantly improved in 83% (10/12) of
      cases, following 1-28 weeks of treatment. Six patients (35%), however, were
      unable to tolerate rIFN-alpha, on account of weight loss, myalgia and mental
      changes. Overall, alpha-interferon therapy significantly improved venesection
      requirements, MCV and PCV values, platelet counts, pruritus scores and the degree
      of splenomegaly. Analysis of pooled published data (100 evaluable patients,
      including the present study) revealed an overall CR of 60%, a PR of 27%, and a
      failure rate of 13%. Significant pruritus control (> 50% improvement) occurred in
      77% of cases. rIFN-alpha appears to be an effective therapy for PV-associated
      myeloproliferation and/or pruritus, although side-effects remain a concern. Long
      term studies are now indicated to determine if the natural history of the disease
      is altered, in particular whether the incidence of myelofibrosis and/or leukaemic
      transformation is reduced.

PMID- 8562412
TI  - Proto-oncogene c-mpl is involved in spontaneous megakaryocytopoiesis in
      myeloproliferative disorders.
AB  - Spontaneous megakaryocytic colonies (CFU-MK) formation without the addition of
      Meg-CSA in myeloproliferative disorders (MPD) has been reported by many
      laboratories. The mechanism by which this occurs is still unknown. In our
      previous work we have found that the spontaneous colonies persisted in serum-free
      agar culture although the colony cells were smaller and the colony numbers fewer
      than in plasma clot culture and that monoclonal antibodies against IL3, IL6 and
      GM-CSF had no inhibitory effect on spontaneous CFU-MK in both semisolid cultures.
      Recently, proto-oncogene c-mpl and c-mpl ligand, thrombopoietin (TPO), have been
      shown to specifically participate in the regulation of normal human
      megakaryocytopoiesis. In order to test the hypothesis that c-mpl, c-mpl ligand
      pathway is involved in the spontaneous growth of megakaryocyte progenitors, we
      investigated mRNA expressions of c-mpl and TPO in cells grown in serum-free
      liquid culture using RT-PCR. The c-mpl expression was detected in the cultured
      cells from all nine patients (six with ET, two with PV, one with PMF) who had
      spontaneous CFU-MK in clonal assays. However, none of the patients expressed TPO
      mRNA in these cells. Pre-incubation of nonadherent mononuclear cells with
      thioester-modified antisense oligodeoxynucleotide to c-mpl at a concentration of
      6 microM significantly decreased the cloning efficiency of spontaneous
      megakaryocyte growth by 42.5% (P < 0.05) in plasma clot assay (seven with ET, one
      with PV) and 69.6% (P < 0.05) in serum-free agar culture (six with ET, one with
      PV). In control experiments the introduction of a scrambled oligomer to antisense
      oligodeoxynucleotide had no such effect on spontaneous colony formation. These
      results indicate that c-mpl exerts an important effect in the growth of
      spontaneous megakaryocytopoiesis in MPD.

PMID- 8562413
TI  - Serum neural cell adhesion molecule in multiple myeloma and other plasma cell
      disorders.
AB  - Serum embryonic neural cell adhesion molecule (eNCAM) levels were measured at
      diagnosis in 92 patients with plasma cell disorders. Significantly elevated
      levels of serum eNCAM were detected in patients with multiple myeloma when
      compared to both normal controls and patients with monoclonal gammopathy of
      uncertain significance (MGUS). Very high levels of serum eNCAM were seen in
      patients with high tumour burdens. There was a significant correlation between
      serum eNCAM and beta 2-microglobulin (beta 2m) (r = 0.33; P = 0.002), but not
      between serum eNCAM and C-reactive protein or serum albumen. There was a trend
      towards longer survival for patients with low serum NCAM. The median survival of
      the low serum eNCAM group (eNCAM < 20 U/ml) was 36 months compared to 16 months
      for the high serum eNCAM group (log rank test chi 2 = 2.42, P = 0.1). Serum eNCAM
      is a new marker of tumour mass in multiple myeloma and correlates with clinical
      stage and beta 2m. Patients with low serum eNCAM levels may have a survival
      advantage. Serum eNCAM warrants further evaluation as a tumour marker and
      prognostic factor in multiple myeloma.

PMID- 8562414
TI  - Blood clonal B-cell excess in patients with monoclonal gammopathy of undetermined
      significance (MGUS): association with malignant transformation.
AB  - Fifty-seven patients with monoclonal gammopathy of undetermined significance
      (MGUS) were analysed for the presence of blood clonal B-cell excess (CBE),
      defined as a lymphocyte surface membrane kappa/lambda light chain ratio outside
      the normal range (> 3.5 in kappa-type MGUS and < 0.9 in lambda-type MGUS). 15
      patients (26%) had a CBE. The patients were followed for a median time of 8.4
      years (range 0.5-20.2). Eight of the 15 CBE+ MGUS patients (53%) developed a B
      cell malignancy as compared to 7/42 patients (17%) in the CBE group and the
      difference in event-free (malignancy-free) observation time was statistically
      significant (P = 0.01). Cox's regression analysis showed that the presence of CBE
      was the most powerful predictor of progression to a malignant disease. Two
      patients with a normal kappa/lambda ratio at first test were analysed repeatedly
      during follow-up. Subsequently, a CBE appeared which gradually increased in size
      preceding the clinical diagnosis of a malignant disease.

PMID- 8562415
TI  - Ultrastructural changes during adhesion and migration of pre-B lymphoid leukaemia
      cells within bone marrow stroma.
AB  - The ultrastructural changes in leukaemic cells on initial contact with, and
      during migration into, layers of bone marrow stroma in vitro were examined in a
      variety of types of acute leukaemia and leukaemic cell lines. Bone marrow
      fibroblasts (BMF) were grown on polycarbonate microporous membranes, and acute
      leukaemia cells added to cultures and allowed to adhere to BMF for variable
      periods of time before fixation. Acute lymphoblastic leukaemia (ALL) blasts
      showed rapid development of surface membrane microvilli on contact with BMF
      layers. ALL blasts, and the pre-B ALL cell line NALM-6, showed evidence of
      movement in to the BMF layer within 15-30 min, with intrusion of extended
      cytoplasic processes into gaps between BMF cytoplasm. ALL cells were frequently
      seen within the layers of fibroblasts after 30 min incubation, and had pronounced
      morphological changes, with pseudopodia and attenuated and elongated microvilli
      interdigitating with the surface of fibroblasts or with strands of extracellular
      matrix material. Changes were also noted in the surface membrane of BMF adjacent
      to ALL cells, with invagination of the cytoplasmic membrane and formation of
      micropits. In contrast to the migratory behaviour of pre-B ALL cells, migration
      was not observed with acute myeloid leukaemia cells or other leukaemic cell
      lines. These cells showed membrane activation, with variable degrees of
      microvillous formation, and in some cases insertion of pseudopodia into BMF
      layers, but migration was not observed. Ultrastructural immunogold labelling was
      carried out to determine the localization of leukaemic adhesion molecules and
      their ligands on BMF. This demonstrated that beta 1 integrins were largely
      localized to the contact surfaces of both ALL blasts and fibroblasts, with VCAM-1
      expressed only on the surface of BMF. These observations confirm the specificity
      of migratory behaviour for pre-B leukaemic cells, and indicate that a complex
      pattern of surface and intracellular events mediate this process, including the
      expression of beta 1 integrins and VCAM-1 at the sites of insertion of leukaemic
      cells between fibroblast margins.

PMID- 8562416
TI  - Studies of P-glycoprotein in chronic myelogenous leukaemia patients: expression,
      activity and correlations with CD34 antigen.
AB  - Over-expression of the P-glycoprotein (Pgp), transmembrane drug efflux pump, has
      been shown to cause multidrug resistance of tumour cells (MDR). To investigate
      the clinical significance of Pgp expression for chronic myeloid leukaemia (CML)
      diagnosis and monitoring we have studied 38 CML patients in various phases of the
      disease (chronic phase, CP; accelerated phase, AP; blast crisis, BC). Anti-Pgp
      monoclonal antibody UIC2 and FACScan analysis were used. Pgp functional activity
      was investigated by evaluation of verapamil influence upon rhodamine 123 efflux
      from the cells. Correlations between Pgp and CD34 expression were investigated.
      In CP, Pgp-expressing cells were found in 2/14 patients; in one of them Pgp
      proved to be non-functional. There were few Pgp-expressing cells in AP cases. The
      group of BC patients consisted of cases resistant to chemotherapy. This gave us
      the opportunity to consider whether drug resistance of BC CML patients is
      preferentially connected with Pgp-mediated MDR. 11/22 BC patients had 20% or more
      of Pgp-expressing blasts in the peripheral blood. In all four Pgp+ BC cases
      studied for Pgp activity this protein was functional. Only 4/22 BC patients
      demonstrated large (40% or more) fractions of Pgp+ blasts. Moreover, sequential
      studies of 11 BC CML patients during treatment revealed an increase in the number
      of Pgp-expressing cells in only two cases. This suggests that Pgp+ cells did not
      often accumulate in BC CML patients due to chemotherapy and are the cause of drug
      resistance in only a few cases. A positive correlation between Pgp and CD34
      expression was found (r = 0.69; P = 0.0004). 3/22 BC CML patients had large
      fractions of both Pgp+ and CD34+ blasts in their peripheral blood. The BC CML
      patients with this immunophenotype of blast cells may represent a subtype of BC
      CML resistant to treatment due to Pgp overexpression.

PMID- 8562417
TI  - Effects of myeloid cell growth factors on alkaline phosphatase, myeloperoxidase,
      defensin and granulocyte colony-stimulating factor receptor mRNA expression in
      haemopoietic cells of normal individuals and myeloid disorders.
AB  - The mRNA expression of alkaline phosphatase (ALP), myeloperoxidase (MPO),
      defensin and G-CSF receptor (G-CSFR) in bone marrow cells of normal individuals
      and myeloid disorders, with or without in vitro stimulation by myeloid cell
      growth factors, i.e. G-CSF, GM-CSF and IL-3, were examined as markers for myeloid
      cell differentiation in both mononuclear cell (MNC) and polymorphonuclear cell
      (PMN) fractions. Without any stimulation, ALP mRNA was expressed only in PMNs, G
      CSFR mRNA in PMNs were expressed stronger than in MNCs; both MPO and defensin
      mRNA were expressed to the same degree in both fractions. With stimulation, the
      ALP mRNA expression in both fractions was strongly enhanced by G-CSF, but the
      expression was inhibited by GM-CSF and/or IL-3. MPO mRNA expression was
      stimulated by G-CSF and/or GM-CSF in MNCs. G-CSFR mRNA expression was enhanced by
      G-CSF in both fractions. Defensin mRNA expression was inhibited by G-CSF. In
      cases of myelodysplastic syndrome and chronic myelogenous leukaemia which display
      a suppressed maturation of myeloid cells, our results demonstrated an almost
      normal response to these growth factors. Our results suggest that studies on
      these myeloid marker mRNA expressions would provide more knowledge about the
      differentiation state and cytokine reactivity of myeloid cells in normal
      individuals as well as various disorders.

PMID- 8562418
TI  - Human bone marrow stromal cells prevent apoptosis and support the survival of
      chronic lymphocytic leukaemia cells in vitro.
AB  - Leukaemic cells from most cases of B-chronic lymphocytic leukaemia die rapidly by
      apoptosis in vitro unless they are cultured in the presence of interleukin-4 or
      interferon alpha or gamma. We now report prolonged survival of purified CLL cells
      cultured on bone marrow (BM) derived stromal cells in the absence of exogenous
      growth factors. In 10 cases of CLL examined 0-61% (mean 14.7%) of the cells were
      viable after 10 d culture in medium alone, whereas in the presence of BM stromal
      cells 10-102% (mean 47.0%) of cells were recovered alive (P < 0.005) in 7/10
      cases of CLL, cells remained viable after 30 d of culture in BM stromal cells
      with cell recovery of 12-65%. These long-term cultured CLL cells were Epstein
      Barr virus negative, shown by the failure to detect the ENBA-2 and BZLF1 genes of
      EBV by PCR analysis. Identity between day 0 and day 30 CLL cells was demonstrated
      by sequence analysis of their clonal IgH CDR3 region. Adherence of CLL cells to
      BM stromal cell layers was critical for their protection from apoptosis.
      Separation of CLL cells from stroma by 0.45 micron culture filters resulted in
      loss of the protective effect of the stromal cells. Stromal cells were also able
      to protect CLL cells from hydrocortisone-induced apoptotic cell death. Our
      findings provide an in vitro system that can be used to analyse the growth
      requirements of CLL cells and their chemosensitivity in an in vitro environment
      that mimics the in vivo milieu.

PMID- 8562419
TI  - The developmental relationships of the neural tube and the notochord: short and
      long term effects of the notochord on the dorsal spinal cord.
AB  - Patterning of the ventral half of the neural tube results from the inductive
      influence of the notochord and of the floor plate. We have studied here the
      effect of an ectopically grafted notochord on the development of the dorsalmost
      part of the neural tube i.e. roof plate and alar plates. We show that at their
      early stages, dorsal genes are repressed by the dorsal graft of a notochord, as
      shown previously in other studies. We found also that when the notochord is
      implanted in a mediodorsal position on top of the roof plate (and not laterally
      as previously performed in other studies) the genes specifics of the floor plate
      are not induced, and motoneurons do not differentiate. The notochord prevents the
      formation of the medial septum from roof plate cells and induces their active
      proliferation between E5 and E7. Roof and dorsal alar plates derived cells start
      to die from E7 onward leaving a dorsally truncated spinal cord. If the notochord
      is grafted at 20 degrees-30 degrees from the sagittal plane ventral genes and
      structures are induced and the roof plate differentiates normally. We conclude
      that roof plate cells exhibit a specific response to notochord signals, the short
      range effect of which is thus strikingly demonstrated.

PMID- 8562420
TI  - Expression of protein tyrosine phosphatase genes during oogenesis in Drosophila
      melanogaster.
AB  - The spatial and temporal expression of seven Drosophila protein tyrosine
      phosphatase genes during oogenesis was examined by whole mount in-situ
      hybridization of antisense RNA probes to ovaries. Our observations indicate
      diverse expression patterns consistent with multiple roles for protein tyrosine
      phosphatases in the ovary. DPTP99A and corkscrew transcripts are expressed in
      follicle cells, consistent with possible roles in the EGF receptor signaling
      pathway. Transcripts from corkscrew and DPTP10D are detected in the germline
      during oogenesis and localized to the oocyte during egg chamber development.
      Localization of the two transcripts is disrupted by mutations in egalitarian and
      Bicaudal D. DLAR and DPTP4E transcripts are found in the germline during the same
      developmental stages as DPTP10D transcripts, but their transcripts are not
      localized to the oocyte. DPTP61F transcription is detected only after stage 6 of
      oogenesis. After stage 10B these transcripts are transported to the oocyte; thus
      ovarian transcription of DPTP61F may reflect a maternal contribution of the mRNA
      for later use during embryogenesis. DPTP69D transcripts are sequestered in the
      nucleus from stage 7 to stage 10, and then released to the cytoplasm. Our
      observations suggest that the export of DPTP69D mRNA from the nucleus is
      temporally regulated during oogenesis.

PMID- 8562421
TI  - Selection and characterization of sequences with high affinity for the engrailed
      protein of Drosophila.
AB  - The engrailed gene helps to direct Drosophila melanogaster development by
      encoding a homeodomain-containing DNA binding protein. To identify genes whose
      transcription engrailed regulates, we developed a method to isolate genomic
      sequences to which engrailed protein binds with high affinity. Fragments of
      genomic DNA were fractionated on an engrailed protein affinity column, and
      fragments that were retained in the presence of 0.4-1.0 M KCl were isolated and
      cloned. The isolated fragments include regions of the engrailed and cubitus
      interruptus gene promoters, both of which are candidate targets of engrailed, and
      most fragments contain regions that engrailed protein protects from DNaseI
      digestion. Chromosomal deletions that remove some of the engrailed binding sites
      (located either at 64D, 96B or 99D) interact genetically with engrailed.
      Characterization of a transcript encoded in region 64D revealed its dependence on
      engrailed protein.

PMID- 8562422
TI  - The extra sex combs product contains WD40 repeats and its time of action implies
      a role distinct from other Polycomb group products.
AB  - The extra sex combs (esc) gene product is a transcriptional repressor of homeotic
      genes. Although it is classified in the Polycomb group (PcG) on the basis of
      phenotypic criteria, it is distinct from most other PcG repressors in its time of
      action during development. We describe the temporal profile of esc mRNA
      expression during embryogenesis and the stage-specific rescue of esc mutants with
      a heat shock-inducible esc cDNA transformation construct. Both experiments
      support the idea that esc product plays an early, transient role in repression of
      homeotic genes. We also present the sequence of a full-length esc cDNA. The
      predicted esc protein is composed primarily of multiple copies of a repeat motif,
      termed the WD40 repeat, which are likely used in protein-protein contact. We
      provide evidence that individual copies of the esc WD40 repeats are needed for
      function in vivo. We suggest that esc protein is an adaptor that binds to
      multiple protein partners and assists in the assembly or targeting of other PcG
      proteins.

PMID- 8562423
TI  - Behavior of extramacrochaetae mutant cells in the morphogenesis of the Drosophila
      wing.
AB  - The gene extramacrochaetae (emc) encodes a non-basic Helix-loop-helix (HLH)
      protein that interacts and antagonises other basic-HLH proteins. The expression
      pattern of emc, and the phenotype of lethal emc alleles indicate that this gene
      is operative in several developmental processes. Here we study the requirements
      for emc during cell proliferation and vein differentiation in the wing. Mosaic
      analysis of hypomorphic conditions of emc reveals the tendency of mutant cells to
      proliferate along the veins as long stripes. Large clones abuting two adjacent
      veins obliterate the corresponding inter-vein, affecting the size and shape of
      the whole wing. Thus, the emc gene participates in the control of cell
      proliferation within inter-vein regions in the wing. Similar effects were found
      in the haltere and in the leg. The behavior of emc cells in genetic mosaics
      indicate that (1) proliferation is locally controlled within inter-vein sectors,
      (2) cells proliferate according to their genetic activity along preferential
      positions in the wing morphogenetic landscape and (3) cell proliferation in the
      wing is integrated by 'accommodation' between mutant and wild type cells.

PMID- 8562424
TI  - The dosage compensation regulators MLE, MSL-1 and MSL-2 are interdependent since
      early embryogenesis in Drosophila.
AB  - We have analyzed the expression pattern and localization of MLE, MLS-1, MSL-2,
      and histone H4Ac16 during embryogenesis to determine when msl-dependent dosage
      compensation begins. Maternal MSL-1 and MLE are present in both sexes at
      fertilization. MSL-2 lacks a maternal component, and male-specific zygotic
      expression is detectable at the end of blastoderm. During germ band extension,
      MSL-1, MSL-2, MLE, and histone H4Ac16 display coincident sub-nuclear localization
      in male embryos. In embryos lacking one of the MSL proteins, the sub-nuclear
      localization of the other MSLs and of histone H4Ac16 is not detected. We conclude
      that the MSL proteins associate with the X chromosome and are interdependent
      since early embryogenesis.

PMID- 8562425
TI  - Trans- and cis-acting requirements for blastodermal expression of the head gap
      gene buttonhead.
AB  - The Drosophila gene buttonhead (btd) encodes a zinc-finger protein related to the
      human transcription factor Sp1. btd is expressed in the syncytial blastoderm
      embryo in a stripe covering the anlagen of the antennal, intercalary and
      mandibular head segments. btd has been characterized as a head gap gene, since
      these segments are deleted in btd mutant embryos. We report here that the cis
      acting elements required for btd head stripe expression are contained in a 1 kb
      DNA fragment, located about 3 kb upstream of the promoter. The four maternal
      coordinate systems are necessary for correct btd head stripe expression, likely
      by acting through the 1 kb cis-acting control region. Expression of the btd head
      stripe depends on the anterior morphogen encoded by the gene bicoid (bcd). bcd
      dependent activation also involves the activity of the morphogens of the
      posterior and dorsoventral systems, hunchback and dorsal, respectively, which act
      together to control the spatial limits of the expression domain. Finally, the
      terminal system takes part in the regulation of btd head stripe expression by
      enhancing activation at low levels of activity and repression at high levels of
      activity.

PMID- 8562426
TI  - Dmcdc2 kinase is required for both meiotic divisions during Drosophila
      spermatogenesis and is activated by the Twine/cdc25 phosphatase.
AB  - We have analyzed the requirement for Drosophila cdc2 kinase during
      spermatogenesis after generating temperature-sensitive mutant lines (Dmcdc2ts) by
      re-constructing mutations known to result in temperature sensitivity in fission
      yeast cdc2+. While meiotic spindles and metaphase plates were never formed in
      Dmcdc2ts mutants at high temperature, chromosomes still condensed in late
      spermatocytes and spermatid differentiation (sperm head and tail formation)
      continued. The same phenotype was also observed in twine and twine, Dmcdc2ts
      double mutant testes, consistent with the idea that the cdc2 kinase activity
      required for meiotic divisions is activated by the Twine/cdc25 phosphatase.
      Confirming this notion, we find that ectopic expression of the String/cdc25
      phosphatase, which is known to activate the cdc2 kinase before mitosis, results
      in a partial rescue of meiotic divisions in twine mutant testis.

PMID- 8562427
TI  - Induction of a secondary embryonic axis in zebrafish occurs following the
      overexpression of beta-catenin.
AB  - Formation of the vertebrate axis may involve a Wnt signaling cascade similar to
      the Drosophila wingless pathway. Zebrafish wnt8 is a candidate for involvement in
      axis specification insofar as it is expressed maternally and when overexpressed
      it can induce goosecoid, a transcription factor normally expressed in the
      embryonic shield. In this study we demonstrate that beta-catenin, a cadherin
      associated protein in the Wnt pathway, is expressed maternally in zebrafish and
      is widely distributed in the early embryo. Overexpressing beta-catenin in early
      zebrafish embryos induces goosecoid and ntl, ultimately leading to a duplication
      of a complete secondary axis. These data are consistent with the involvement of
      beta-catenin in a Wnt signaling pathway which is involved in mesoderm induction
      in zebrafish.

PMID- 8562428
TI  - Differentiation of pluripotent embryonic stem cells into the neuronal lineage in
      vitro gives rise to mature inhibitory and excitatory neurons.
AB  - Embryonic stem (ES) cells represent a suitable model to analyze cell
      differentiation processes in vitro. Here, we report that pluripotent ES cells of
      the line BLC 6 differentiate in vitro into neuronal cells possessing the complex
      electrophysiological and immunocytochemical properties of postmitotic nerve
      cells. In the course of differentiation BLC 6-derived neurons differentially
      express voltage-dependent (K+, Na+, Ca2+) and receptor-operated (GABAA, glycine,
      AMPA, NMDA receptors) ionic channels. They generate fast Na(+)-driven action
      potentials and are functionally coupled by inhibitory (GABAergic) and excitatory
      (glutamatergic) synapses as revealed by measurements of postsynaptic currents.
      Moreover, BLC 6-derived neurons express neuron-specific cytoskeletal, cell
      adhesion and synaptic vesicle proteins and exhibit a Ca(2+)-dependent GABA
      secretion. Thus, the ES cell model enables the investigation of cell lineage
      determination and signaling mechanisms in the developing nervous system from a
      pluripotential stem cell to a differentiated postmitotic neuron. The in vitro
      differentiation of neurons from ES cells may be an excellent approach to study by
      targeted gene disruption a variety of neuronal functions.

PMID- 8562429
TI  - Chemistry of nitric oxide: biologically relevant aspects.
AB  - This discussion of NO chemistry has addressed only certain aspects that may be of
      biological relevance. It is not meant to be a comprehensive in-depth treatment of
      general NO chemistry. For more information regarding the chemistry of NO and
      related nitrogen oxides, the reader is referred to a number of reviews (Ragsdale,
      1973; Schwartz and White, 1983; Vosper, 1975; McCleverty, 1979; Gilbert and
      Thomas, 1972; Bonner and Hughes, 1988). Hopefully, it has become evident that an
      appreciation and knowledge of the chemistry of NO are key to understanding its
      physiological utility as well as its toxicology. It appears that Nature exploits
      a variety of the unique chemical aspects of NO in order to attain the needed
      physiological specificity. For example, the specific activation of guanylate
      cyclase by NO is most likely due to its unique binding properties to iron hemes.
      Also, the inherent lack of reactivity of NO makes it a fairly innocuous species
      unless it is coupled with other radical species, such as O2-. This chemical
      property thus allows NO to be utilized as a physiological messenger molecule and,
      under certain conditions, as a cytotoxic effector molecule as well.

PMID- 8562430
TI  - Regulation of the expression of the inducible isoform of nitric oxide synthase.

PMID- 8562431
TI  - Regulation and function of inducible nitric oxide synthase during sepsis and
      acute inflammation.
AB  - During sepsis and inflammation profound changes in physiological function are
      induced by a variety of mediators, including endotoxin, various cytokines, and
      NO. Many of these mediators, in addition to their other functions, induce the
      synthesis of NO through the induction of iNOS within a variety of cell types. The
      regulation of iNOS expression is quite complex. Of interest is the fact that the
      functions of NO during sepsis range from modulating perfusion to mediating
      cytotoxicity. In addition, it is unique that many tissues not characterized as
      being involved in immune function express iNOS in a manner similar to that of
      tissues involved in immune function. The role of NO during episodes of acute
      inflammation appears to be a protective one; however, there are examples of
      chronic localized inflammation in both animal and human models which suggest that
      chronic iNOS expression may be detrimental. Further investigations into the
      regulation and function of NO in both the acute and chronic settings are
      necessary in order to fully understand this small yet unique molecule.

PMID- 8562432
TI  - Reactions between nitric oxide, superoxide, and peroxynitrite: footprints of
      peroxynitrite in vivo.

PMID- 8562433
TI  - Expression and expressional control of nitric oxide synthases in various cell
      types.

PMID- 8562434
TI  - Control and consequences of endothelial nitric oxide formation.
AB  - The intention of this chapter is to give a brief overview of the continuously
      expanding field of endothelium-derived NO. Over the past few years it has become
      apparent that the mechanisms controlling the activation of NOS are more complex
      than was previously thought, with factors such as pHi, [Ca2+]i, shear stress, and
      gender all contributing to the control of "basal" NO production as well as the
      regulation of NOS levels in endothelial cells. The list of the functional
      consequences of endothelial NO formation has also grown, with antiproliferative,
      antihypertensive, and antiatherogenic effects all being described. Recent
      advances at the molecular biology level have facilitated the pioneering of a
      whole new field of research, and a number of groups have shown that NO can
      modulate the expression of several genes, such as that encoding MCP-1, an effect
      that is probably due to an interaction between NO and transcription factors.
      Further elucidation of the signals that influence the production and actions of
      NO will, without doubt, further the understanding of numerous physiological and
      pathophysiological processes.

PMID- 8562435
TI  - Control of electron transfer in neuronal nitric oxide synthase by calmodulin,
      substrate, substrate analogs, and nitric oxide.

PMID- 8562436
TI  - Negative modulation of nitric oxide synthase by nitric oxide and nitroso
      compounds.
AB  - These observations clearly indicate that NO inhibits NOS activity and that nNOS
      and eNOS are more sensitive than iNOS to the inhibitory action of NO. Not only
      exogenously added NO but also enzymatically generated NO inhibits the activity of
      nNOS and eNOS. The mechanism by which NO inhibits NOS appears to involve the heme
      iron prosthetic group of NOS. Moreover, the oxidation state of the heme iron is
      critical in determining the magnitude of inhibition of NOS by NO. Conditions that
      favor the higher oxidation state of FeIII markedly increase the inhibitory action
      of NO, whereas conditions that favor the lower oxidation state of FeII markedly
      decrease the inhibitory action of NO. One of the cofactor roles of
      tetrahydrobiopterin may be to reduce the negative-feedback effect of NO on NOS by
      favoring the formation of the ferrous heme state in NOS. The inhibitory influence
      of NO on eNOS, albeit indirectly, was also observed in vascular endothelial
      cells, arterial rings, and in vivo in the perfused rabbit hindquarters vascular
      bed. Excess NO in the form of NO donor compounds inhibited the endothelium
      dependent formation of EDRF/NO in response to endothelium-dependent vasorelaxants
      such as acetylcholine and bradykinin without influencing the relaxant effect of
      NO itself. These studies are consistent with the view that enzymatically
      generated NO may play an important negative-feedback regulatory role on eNOS, and
      therefore on vascular endothelial cell function. Several biological implications
      of a negative-feedback modulatory effect by NO on constitutive isoforms of NOS
      are evident. In nonadrenergic-noncholinergic transmission, in which NO is
      believed to be the principal inhibitory neurotransmitter (Sanders and Ward, 1992;
      Rand, 1992; Rajfer et al., 1992), NO may regulate its own synthesis, and
      therefore the neurotransmission process. Excess NO production may be undesirable
      because of the potential of NO or a reaction product of NO to elicit cytotoxic
      effects. Many extraneuronal factors could also contribute to decreasing the
      potentially cytotoxic actions of NO. For example, reduced hemoproteins such as
      hemoglobin, myoglobin, and/or their oxygen adducts could inactivate NO, as could
      superoxide anion generated in the vicinity of NO. In vascular endothelial cells
      either enzymatically generated NO or the presence of exogenously added NO in the
      form of nitrovasodilator drugs could diminish the vasodilator responses to
      endothelium-dependent relaxants and flow or shear stress. Although iNOS is less
      sensitive than either eNOS or nNOS to inhibition by NO, the generation of
      relatively large quantities of NO by iNOS within the confines of a cell may lead
      to a negative-feedback effect. The concomitant generation of superoxide anion by
      the same or adjacent cells could result in a diminished negative-feedback effect
      because of the rapid reaction between NO and superoxide anion to form
      peroxynitrite. Thus, NO production would increase and there would be increased
      peroxynitrite formation as well, which would result in enhanced cytotoxicity,
      provided that peroxynitrite is a cytotoxic species. Alternatively, iNOS may be
      conveniently insensitive to NO in order to allow for the generation of large
      quantities of NO for the purpose of producing cytotoxic effects.

PMID- 8562437
TI  - Regulation of nitric oxide synthase: role of oxygen radicals and cations in
      nitric oxide formation.

PMID- 8562438
TI  - Why tetrahydrobiopterin?

PMID- 8562439
TI  - Nitric oxide and cGMP signaling.

PMID- 8562440
TI  - Nitric oxide and intracellular heme.
AB  - Figure 2 depicts a working hypothesis for these results. Activation of .NO
      synthesis results in nitrogen oxide-induced loss of protein-bound heme from CYP
      proteins, which remain relatively intact. This heme liberation results in a
      decrease in heme synthesis (decreased ALAS) and an increase in heme degradation
      (increased HO). In addition, .NO synthesis results in direct inhibition of
      ferrochelatase, which further contributes to inhibition of heme synthesis. There
      also appears to be a mechanism to repair or resynthesize CYP after .NO synthesis
      is inhibited. Finally, a result of this effect may be protection against cellular
      injury, since increased HO is an important response against cellular injury from
      a variety of insults.

PMID- 8562441
TI  - High-level expression of biologically active soluble guanylate cyclase using the
      baculovirus system is strongly heme-dependent.

PMID- 8562442
TI  - cGMP signaling through cAMP- and cGMP-dependent protein kinases.

PMID- 8562443
TI  - Physiological and toxicological actions of nitric oxide in the central nervous
      system.
AB  - NO has clearly revolutionized our thinking about aspects of neurotransmission and
      neuronal signaling. It has also radically altered our thoughts about how synaptic
      transmission takes place. NO is emerging as an important regulator of a variety
      of physiological processes; however, under certain conditions of excessive
      formation, NO is emerging as an important mediator of pathological nervous tissue
      damage. Understanding the role of NO in these processes will hopefully lead to
      the development of selective therapeutic agents and to a better understanding of
      basic processes underlying normal and pathological neuronal functions.

PMID- 8562444
TI  - S-nitrosothiols: chemistry, biochemistry, and biological actions.

PMID- 8562445
TI  - Glyceraldehyde-3-phosphate dehydrogenase: a target for nitric oxide signaling.

PMID- 8562446
TI  - Nitric oxide donors: biochemical pharmacology and therapeutics.
AB  - The NO donors are a diverse group of agents with unique chemical structures and
      biochemical requirements for generation of NO. The differences in biochemistry
      and metabolism may, in turn, cause differences in their pharmacology and
      therapeutic actions. A thorough understanding of the biochemical pharmacology of
      NO donors and factors controlling their therapeutic activity would facilitate the
      optimal use of these agents as chemical carriers of NO, and the development of
      newer agents than can selectively modulate the many physiological actions of NO.

PMID- 8562447
TI  - Nitric oxide donors: a continuing opportunity in drug design.

PMID- 8562448
TI  - Nitric oxide and peripheral adrenergic neuromodulation.

PMID- 8562449
TI  - A study on tumor necrosis factor, tumor necrosis factor receptors, and nitric
      oxide in human fetal glial cultures.

PMID- 8562450
TI  - Inhaled nitric oxide, clinical rationale and applications.

PMID- 8562451
TI  - Oxygen radical-nitric oxide reactions in vascular diseases.

PMID- 8562452
TI  - Inhaled nitric oxide therapy of pulmonary hypertension and respiratory failure in
      premature and term neonates.

PMID- 8562453
TI  - Clinical applications of inhaled nitric oxide in children with pulmonary
      hypertension.
AB  - We have presented our experience with the use of inhaled nitric oxide in children
      with congenital heart disease and pulmonary hypertension, which indicates that
      nitric oxide is a selective pulmonary vasodilator that may improve patient
      management, particularly after surgical procedures requiring cardiopulmonary
      bypass. Indeed, we have now seen several patients in whom all resuscitative
      maneuvers for the treatment of pulmonary hypertensive crises were unsuccessful
      until inhaled nitric oxide was added to the therapeutic regimen. In addition, our
      studies using inhaled nitric oxide as an investigational probe point toward
      endothelial injury as a contributor to post-cardiopulmonary bypass pulmonary
      vasoconstriction. Inhaled nitric oxide relieves pulmonary vasoconstriction
      associated both with left atrial or pulmonary venous hypertension and following
      the relief of mitral valve or pulmonary venous obstruction. Absence of a response
      on the usually reactive pulmonary vascular bed of the neonate should prompt a
      careful search for anatomic, and possibly surgically remediable, pulmonary
      vascular obstruction. In the short term nitric oxide is less effective in the
      older patient with obliterative pulmonary vascular disease. It is possible that
      recent experimental work with long-term nitric oxide inhalation might be
      applicable to this group of patients. Nitric oxide may have a unique role in the
      management of the patient after lung transplantation, as it both reduces right
      ventricular afterload and improves intrapulmonary shunting. Is nitric oxide the
      ideal agent for testing pulmonary vascular reactivity? Nitric oxide is simple to
      deliver by either mask or ventilator and, as a trial of vasoreactivity over 15
      min, remains free of side effects that might be encountered during long-term
      administration, such as methemoglobinemia or nitrogen dioxide toxicity. Indeed,
      no patient developed significant methemoglobinemia after a trial of nitric oxide
      and neither was a level of nitrogen dioxide above 1 ppm registered during the
      administration. Thus, nitric oxide gas fulfills many of the ideal
      characteristics, as suggested by Rubin,92 required of a drug to test the acute
      responsiveness of the pulmonary circulation. It has better pulmonary dilating
      effects than systemic, a short half-life, and minimal adverse effects and it can
      be both easily and quickly administered. Whether it is able to reliably predict
      the effect of long-term administration of orally active agents awaits
      confirmation. Certainly, inhaled nitric oxide is rapidly becoming the standard
      agent to test pulmonary vascular reactivity during diagnostic cardiac
      catheterization at our institution.

PMID- 8562454
TI  - Nitric oxide synthases: gene structure and regulation.
AB  - The NOSs are a family of complex enzymes that catalyze the five-electron
      oxidation of L-arginine to form NO and L-citrulline. They are best characterized
      as cytochrome P-450-like hemeproteins that depend on molecular oxygen, NADPH,
      flavins, and tetrahydrobiopterin. The three human NOS isoforms identified to
      date, ecNOS, nNOS, and iNOS, are found on human chromosomes 7, 12, and 17,
      respectively. Regulation of NO synthesis and release occurs at the levels of
      enzyme activity and mRNA synthesis. The nNOS mRNA is structurally diverse as a
      consequence of alternative promoters and alternate splicing. The iNOS gene is
      predominantly regulated at the level of transcription by synergistic combinations
      of proinflammatory cytokines and bacterial wall products. Changes in mRNA levels
      of the ecNOS following endothelium activation are mediated by altered rates of
      transcription as well as by the intriguing process of changes in mRNA stability.
      Given the essential role of the NO pathway in a wide variety of physiological and
      pathophysiological process, it is possible that the three isoforms of NOS
      contribute to polygenic genetic diversity in neurological, immune, and
      cardiovascular biology. Further studies are needed to determine the mechanisms of
      gene regulation of NOS in health and disease.

PMID- 8562455
TI  - Transcription of the human neuronal nitric oxide synthase gene in the central
      nervous system is mediated by multiple promoters.

PMID- 8562456
TI  - Progress in the measurement of ciliary beat frequency by automated image
      analysis: application to mammalian tracheal epithelium.
AB  - The investigations on the activity of respiratory ciliae in vivo are of
      considerable interest for the study of physiopathological disorders resulting
      from chronic infection or inhaled pollutants. We present an image analysis method
      for the measurement of ciliary beat frequency on mammal or human in vivo samples.
      Videofilm sequences of samples placed under the microscope were analyzed frame by
      frame by image analysis. The operator defines on the screen several areas of
      interest on the cell apex. The variation of grey levels in each areas allows the
      calculation of ciliary beat parameters. This method permits one to investigate
      the effects of pharmacological agents or noxious pollutants on ciliae beating and
      the physiological causes underlying them. Our results on rabbits were in
      agreement with the data published in literature, showing no significant
      difference between intratracheal frequencies obtained at medium and lower levels.
      The upper level near the cracoid cartilage has shown a greater variability than
      the other two levels with higher beating frequencies, a difference of likely
      physiological importance.

PMID- 8562457
TI  - The HOME tutor: a new tool for training in microscope skills.
AB  - AxioHOME is a new concept in microscope design. It is a microscope with a visual
      display unit mounted in the head permitting computer generated displays to be
      projected on to the real microscope image when viewed down the eyepieces. This
      allows the annotation of the microscope image with both text and graphics. The
      AxioHOME system was used for the construction of complex interactive tutorials
      for the training and assessment of students. The basis of a tutorial is that
      features of interest on a microscope slide are indicated to the student who is
      then provided with either information or questions about those features. In turn
      the student can also annotate the slide with comments for later discussion with
      the teacher. The system therefore allows a dialogue between teacher and student.
      The creation of tutorials is time consuming. It takes approximately 10 min of
      teacher time to create 1 min of student time. However since the same tutorial can
      be used by numerous students this releases the teacher from repetitive training.
      The student response to this teaching method has been very positive. The main
      criticism being that insufficient teaching material was available.

PMID- 8562458
TI  - Malignancy associated changes in cervical smears: systematic changes in
      cytometric features with the grade of dysplasia.
AB  - For almost ten years. Malignancy Associated Changes have been consistently found
      by means of high resolution image analysis of apparently normal uterine cervix
      cells. The study was performed on normal intermediate cells randomly selected
      from 1850 cervical smear slides classified as negative, mild dysplasia, moderate
      dysplasia and severe dysplasia. Size and texture features, performed by the Cyto
      Savant software, have shown significant monotonic changes with the grade of
      dysplasia. These findings indicate that the intensity of Malignancy Associated
      Changes are directly related to the severity of the adjacent lesions.

PMID- 8562459
TI  - Quantitative immunochemistry of endothelial cells in cutaneous tissue.
AB  - In vivo endothelial cell exploration in human pathology has been limited by the
      lack of a suitable procedure for quantification of endothelial molecule
      expression. The objective of the present study was the development of a precise,
      simple and rapid image analysis method to quantify dermis endothelial cells and
      associated molecules. Cutaneous tissue sections were labelled by immunoperoxidase
      procedure using a monoclonal anti-von Willebrand factor (vWF) antibody, which
      identifies endothelial cells. The image analysis programme was tested to quantify
      final reaction deposit (DAB) with reference to different anti-vWF antibody
      concentrations. The entire biopsy section was acquired, field by field. Analysis
      was restricted to three dermis zones geodesically defined from epidermis. Optical
      density and area measurements were performed in whole area and in positive areas.
      This work demonstrated the feasibility of endothelial cell study assisted by
      image analysis. Surface labelled by anti-vWF antibody at saturating concentration
      may be considered as an endothelial reference surface, and thus may be useful for
      future quantification of other endothelial molecules.

PMID- 8562460
TI  - Analysis of isolated zymogen granules from rat pancreas using flow cytometry.
AB  - Rat pancreatic zymogen granules were analyzed using flow cytometry to determine
      their heterogeneity with respect to different characteristics such as size (FSC),
      internal complexity (SSC) and membrane permeability to lipophilic and cationic
      dyes using rhodamine-123 as probe. Differences in the chemical composition of the
      membrane were determined using FITC-labeled lectins (concanavalin A, Wheat germ
      agglutinin (WGA) and Tetragonolobus purpureus) displaying specific binding for
      different carbohydrates (D-mannose, N-acetyl D-glucosamine and L-fucose,
      respectively). Finally, the amylase content of zymogen granules was also analyzed
      using an anti-amylase antiserum. Our results show the existence of two
      populations of zymogen granules that can be identified on the basis of their FSC
      and SSC characteristics: a minor population of approximately 5% all zymogen
      granules with larger size (FSC) and internal complexity (SSC), and a major
      population clearly differentiable on the basis of a lower FSC and SSC. Rhodamine
      123 uptake was similar in both subpopulations of zymogen granules. By contrast,
      labeling with fluoresceinated lectins and anti-amylase antiserum showed the
      existence of a higher content on both amylase and the monosaccharide residues
      analyzed for the Z2 zymogen granules. However, it is shown that those differences
      are strongly dependent on the FSC (size) of the granules suggesting that although
      the carbohydrate contents (D-mannose, N-acetyl D-glucosamine and L-fucose) and
      the amount of amylase differed from one granule to another, their concentration
      per granule was similar.

PMID- 8562461
TI  - Loss of cytokeratins in breast cancer cells using multiparameter DNA flow
      cytometry is related to both cellular factors and preparation procedure.
AB  - In breast carcinomas, S-phase fraction calculated after flow cytometric selection
      of epithelial cells improves the prediction of distant recurrence. However, the
      presence of DNA aneuploid cells registered as non-epithelial cells and the
      intertumoural variation of cytokeratin positivity may cause selective loss of
      tumour cells in flow cytometric analysis. In the present study, the expression of
      cytokeratins 8 and 18 was examined by both immunohistochemistry and flow
      cytometry. The proportion of cytokeratin-positive cells was decreased by 25% when
      estimated by flow cytometry compared with immunohistochemistry; however, the
      correlation between these two methods was significant (P < 0.01). Fewer cells
      were cytokeratin-positive in DNA hypodiploid tumours compared with DNA diploid
      and DNA aneuploid tumours (P = 0.006). Also, rapidly proliferating tumours tended
      to have a smaller proportion of cytokeratin-positive tumour cells. Our results
      indicate that loss of cytokeratins in breast cancer cells is related to both
      cellular factors and the preparation procedure.

PMID- 8562462
TI  - Subcutaneous nodules in a patient hyposensitized with aluminium-containing
      allergen extracts: a microanalytical study.
AB  - Electron spectroscopic imaging (ESI) is a recent tool for electron microscopic
      analysis which permits the recognition of the distribution of elements in a
      specimen, with a spatial resolution up to 5 nm. The authors performed the ESI
      together with X-ray microanalysis (EDX) and transmission electron microscopy to
      study granulomatous subcutaneous nodules in a patient who had undergone a
      desensitising therapy with an aluminium-containing vaccine. Aluminium was
      detected both by EDX and ESI, mainly in lysosomes of histiocytes containing
      needle-shaped material in a lucent matrix. However, ESI provided a better
      localization of aluminium with respect to EDX. This result suggests that the
      identification of aluminium-containing structures cannot be obtained only by
      ultrastructural morphology and underlines the utility of a microanalitycal study
      for a correct diagnosis in the presence of a needle-shaped deposition of dense
      material in lysosomes.

PMID- 8562463
TI  - New concepts regarding events that lead to myocardial infarction.
AB  - In addition to new knowledge concerning the mechanisms whereby conventional risk
      factors act, other risk factors have been newly described, such as dietary
      antioxidants, lack of exercise, insulin resistance, excess iron stores, increased
      plasma angiotensin-converting enzyme, and left ventricular hypertrophy. An intact
      endothelium protects both by the formation of nitric oxide, which is a
      vasodilator and also an inhibitor of platelet aggregation and neutrophil
      adhesion, and by manufacturing tissue plasminogen activator. The acute thrombotic
      event occurs with a diurnal variation but may be precipitated by acute exertion,
      especially in untrained individuals, and reflects a balance between
      vasoconstrictory and vasodilatory stimuli from the vascular endothelium, as well
      as procoagulant versus anticoagulant effects of complex balancing systems.
      Increased risk of sudden cardiac death in the morning is thought to be a
      reflection of transient risk factors, such as a blood pressure increase, heart
      rate increase, and changes in coagulation factors, as well as changes in platelet
      aggregation. There is an apparent paradox between the acute effect of exercise in
      promoting sudden cardiac death and the chronic effect of exercise training in
      decreasing the risk of myocardial infarction. The explanation may be that chronic
      exercise training has an inhibitory effect on adrenergic discharge.

PMID- 8562464
TI  - New concepts regarding events that lead to end-stage heart disease.
AB  - Cardiac dysfunction is a progressive process that eventuates in end-stage heart
      failure. This progression involves dilatation and hypertrophy of the left
      ventricle, characterized as left ventricular remodeling. This remodeling results
      in a falling left ventricular ejection fraction, worsening heart failure, and
      increased risk of lethal ventricular arrhythmias. Increased aortic impedance due
      to vasoconstriction, neurohormonal stimulation, and bioenergetic abnormalities
      all may contribute to the remodeling process. Therapeutic efforts aimed at
      halting this progressive process, especially if initiated early in the course of
      the disease, are most likely to exert a favorable effect.

PMID- 8562465
TI  - Primary prevention in patients with coronary heart disease: the APSIS study.
AB  - Symptomatic treatment of patients with angina pectoris is well established and
      consists of nitrates, calcium antagonists, or beta-blockers. All these drugs
      improve symptomatology and reduce signs of ischemia on exercise test or long-term
      electrocardiogram recordings. It is not known, however, whether these drugs also
      improve prognosis. The only drug shown to improve prognosis is aspirin. In order
      to study the prognostic effect of calcium antagonists and beta-blockers, these
      two drugs were compared in the APSIS study.

PMID- 8562466
TI  - Treatment for survivors of acute myocardial infarction: what have we learned from
      large intervention trials?
AB  - The current treatment of survivors of acute myocardial infarction is now largely
      based on sound scientific principles, supported by the results of large and well
      designed clinical trials. These have demonstrated that aspirin, anticoagulants,
      beta-blockers, angiotensin converting enzyme inhibitors, and lipid-lowering
      agents reduce mortality and reinfarction in selected groups of patients. It
      remains uncertain whether these different treatments are additive and whether
      there are beneficial or undesirable interactions. In addition to informing us
      about the effectiveness or otherwise of these and other drugs, we have learned
      much about the conduct, analysis, and limitations of clinical trials in this
      context. The selection of patients for the various treatments is a matter of
      opinion because the results of the trials are open to a variety of
      interpretations. In assessing trials, one must be sure that they have been
      conducted on the intention to treat principle and that surrogate and composite
      end points have not been inappropriately used. In applying the results of trials
      to one's own practice, one must take into account the problems of extrapolation
      and subgroup analysis.

PMID- 8562467
TI  - ACE inhibitors and calcium antagonists in the treatment of congestive heart
      failure.
AB  - The increased mortality after myocardial infarction is related to the risk of
      reinfarction, sudden death, and the development and progression of heart failure;
      in congestive heart failure it is due to the progression of heart failure and
      sudden death. ACE inhibitors have been proven to prevent cardiovascular events,
      especially the progression of heart failure, in postinfarct patients with reduced
      ejection fraction and heart failure in the SAVE and AIRE trials. In patients with
      congestive heart failure, ACE inhibitor treatment has prevented cardiovascular
      death and reduced morbidity due to progressive heart failure in the SOLVD trials.
      In post-myocardial infarction patients, the calcium antagonist nifedipine did not
      affect mortality or morbidity; diltiazem improved prognosis in patients without
      congestive heart failure and in patients with non-Q-wave infarction; and
      verapamil improved prognosis by prevention of reinfarction and sudden death.
      Combination treatment with both verapamil, which has pronounced antiischemic
      properties and prevents sudden death and reinfarction, and an ACE inhibitor,
      which prevents the progression of heart failure, is a possibility for future
      cardiovascular therapy that should be evaluated.

PMID- 8562468
TI  - Vascular protective effects of ACE inhibitors and calcium antagonists:
      theoretical basis for a combination therapy in hypertension and other
      cardiovascular diseases.
AB  - Hypertension is an important cardiovascular risk factor. High blood pressure per
      se is not a disease but a hemodynamic alteration associated with vascular
      disease. Two classes of drugs are especially effective in lowering blood pressure
      and preventing cardiovascular complications, angiotensin converting enzyme (ACE)
      inhibitors and calcium antagonists. The hemodynamic effects of ACE inhibitors and
      calcium antagonists are complementary. While ACE inhibitors inhibit the renin
      angiotensin system and reduce sympathetic outflow, calcium antagonists dilate
      large conduit and resistance arteries. Certain calcium antagonists, such as
      verapamil, lower heart rate. In the blood vessel wall, the local vascular effects
      of ACE inhibitors and calcium antagonists are also complementary. While ACE
      inhibitors inhibit activation of angiotensin I into angiotensin II and prevent
      the breakdown of bradykinin (which stimulates nitric oxide and prostacyclin
      formation), calcium antagonists inhibit the effects of vasoconstrictor hormones
      such as angiotensin II at the level of vascular smooth muscle by reducing calcium
      inflow and facilitating the vasodilator effects of nitric oxide. Calcium
      antagonists reduce smooth muscle cell proliferation and atherosclerosis. In
      hypertensive animals, verapamil and trandolapril normalize endothelial
      dysfunction. In large angiographic trials, nifedipine and nicardipine reduced the
      development of new atherosclerotic plaques. After myocardial infarction,
      verapamil reduces mortality and cardiac events in patients without heart failure.
      In contrast, ACE inhibitors are effective after myocardial infarction in patients
      with impaired left ventricular function. Urinary albumin excretion rate decreases
      during ACE inhibitor therapy or with a calcium antagonist such as verapamil;
      combination of the two drugs has an additive effect. In resistance arteries,
      hypertension is associated with an increased media/lumen ratio. ACE inhibitors,
      but not beta-blockers, markedly improve these structural changes. In summary, ACE
      inhibitors and calcium antagonists have a complementary profile, both in their
      hemodynamic and local vascular action. Hence, combination therapy with these two
      classes of drugs appears particularly useful in patients with hypertension, not
      only to lower blood pressure, but hopefully to achieve improved cardiovascular
      protection.

PMID- 8562469
TI  - Coadministration of calcium antagonists and ACE inhibitors--is a skeptic
      convinced?: a personal view.
AB  - The pathological chain of events that stretches from the earliest atheromatous
      lesion to end-stage myocardial failure and death is amenable to attack in many
      places. It may well prove that a multifaceted intervention offers the best
      therapeutic option. Two important cardiovascular therapies, the calcium entry
      blockers and ACE inhibitors, may offer more than their effects on vascular tone
      and remodeling. Both have actions on the basic process of atheroma. Individually,
      or more challengingly in combination, they may strike at the basic pathogenesis
      of atherosclerosis yet still provide their more general beneficial effect on
      vasomotor tone. Whilst clinical data are yet scant, there is a plausible
      biological basis for their coprescription.

PMID- 8562470
TI  - Vascular complications in hypertension: the VHAS study. Verapamil-Hypertension
      Atherosclerosis Study.
AB  - The VHAS (Verapamil-Hypertension Atherosclerosis Study) Investigators entered
      1464 patients with essential hypertension and blood pressure (BP) values > or =
      160 mmHg systolic and 95 mmHg diastolic (DBP) but excluded those with a DBP > or
      = 115 mmHg, and those with diabetes mellitus or previous myocardial infarction or
      cerebrovascular episodes. Patients were randomly allocated to drug therapy for 2
      years with either slow-release verapamil 240 mg once daily or chlorthalidone 25
      mg once daily, with nonresponders receiving additional captopril 25 mg daily. A
      random group of eligible patients (n = 494) was followed for a more extended
      period (4 years) using beta-mode ultrasound. The end point is the development of
      atherosclerosis detected by ultrasound imaging. The most interesting observation
      thus far is that in this population of middle-aged hypertensives without a
      history of previous cardiovascular events, about two thirds had asymptomatic
      carotid alterations. The study is ongoing.

PMID- 8562471
TI  - Left ventricular hypertrophy and diastolic dysfunction: their relation to
      coronary heart disease.
AB  - Diastolic dysfunction is an early sign in the temporal sequence of ischemic
      events in coronary heart disease. The ischemic cascade, beginning with an oxygen
      demand supply imbalance and metabolic alterations, identifies diastolic disorders
      of the left ventricle (LV) as an early phenomenon, sometimes before systolic
      dysfunction, electrocardiographic changes, or chest pain occur. Although the
      physiology of diastolic function is complex, the factors contributing to
      diastolic disturbances can be differentiated into intrinsic and extrinsic LV
      abnormalities. Intrinsic mechanisms include (a) impaired LV relaxation, (b) the
      complex of LV hypertrophy, and (c) increased LV asynchrony. Myocardial
      hypertrophy leads to an increase of the myocardial mass/volume ratio, and the
      degree of hypertrophy is the main determinant of chamber stiffness. The main, if
      not unique, determinant of myocardial diastolic tissue distensibility is the
      structure and concentration of the collagen. Consequently, tissue stiffness is
      increased in coronary disease by reparative interstitial fibrosis or scar
      following myocardial infarction. In myocardial hypertrophy the LV collagen
      concentration is elevated due to reactive fibrosis. An increase in regional
      asynchrony of LV contraction and relaxation is a result of regional ischemia as
      well as of LV hypertrophy and tissue fibrosis. Factors extrinsic to the LV
      causing diastolic disorders include (a) increased central blood volume, which
      will increase left ventricular pressure without altering the LV pressure-volume
      relation, and (b) ventricular interaction mediated by pericardial restraint,
      which may cause a parallel upward shift of the diastolic LV pressure-volume
      relation. Improved insight into the mechanisms of LV relaxation and filling
      characteristics help in the treatment of LV diastolic dysfunction.

PMID- 8562472
TI  - Terminal differentiation of normal chicken erythroid progenitors: shortening of
      G1 correlates with loss of D-cyclin/cdk4 expression and altered cell size
      control.
AB  - Detailed knowledge is available about the molecular makeup of the cell cycle
      clock in dividing cells. However, comparatively little is known about cell cycle
      regulation during terminal differentiation. Here we describe a primary cell
      system in which this question can be addressed. Normal avian erythroid
      progenitors undergo continuous self-renewal in suspension culture in the presence
      of growth factors and hormones, allowing us to obtain large cell numbers (10(10)
      10(11)). By replacing these "self-renewal factors" with erythropoietin and
      insulin, the cells can be induced to synchronous, terminal differentiation.
      During the first 72 h, the cells undergo five cell divisions. Thereafter, they
      arrest in G1 and complete their maturation into RBC without further divisions.
      Sixteen to 24 h after induction of differentiation, the cell cycle length
      decreased from about 20 to 12 h. This shortened doubling time was due to a
      drastic reduction of G1 (from 12 to 5 h), while S- and G2-phase lengths were not
      affected. At the same time, the differentiating cells underwent an extensive and
      concerted switch in their gene expression pattern. During the subsequent four
      cell divisions, the cell volume decreased from about 300 to less than 70
      femtoliters, but the rate of protein synthesis normalized to cell volume remained
      constant. Interestingly, the shortening of G1 was accompanied by a rapid down
      regulation of D-type cyclins and their partner, cyclin-dependent kinase type 4
      (cdk4), while expression of S- and G2-M-associated cell cycle regulators (cyclin
      A and cdk1/cdc2) remained high until the cells arrested in G1 72-96 h after
      differentiation induction. We conclude that concerted reprogramming of progenitor
      gene expression during erythroid differentiation is accompanied by profoundly
      altered cell cycle progression involving the loss or alteration of cell size
      control at the restriction point.

PMID- 8562473
TI  - In situ effects of interferon on human glioma protein kinase C-alpha and -beta
      ultrastructural localization.
AB  - Transmission electron microscopy was used to determine how immunogold labeling of
      PKC-alpha or -beta is modulated by the antitumor drug IFN (HuIFN alpha-2b) in the
      cytoplasm, membrane structures, and nucleus of rapidly dividing and confluent
      human glioma U-373 cells. Results showed that except for nuclear localization,
      there were no specific cytoplasmic organelles that PKC-alpha or -beta
      translocated to following HuIFN alpha-2b treatment. Electron micrographs of PKC
      beta in proliferating cells depicted 1.34-fold more PKC-beta in the nucleus than
      in the cytoplasm and a 1-min HuIFN alpha-2b (500 units/ml) treatment transiently
      increased PKC-beta immunoreactivity in the cytoplasm (1.95-fold) and nucleus
      (1.97-fold). In confluent cells, incubation with HuIFN alpha-2b for 2 min
      significantly decreased cytoplasmic PKC-beta immunoreactivity by 37%, and no
      change was observed in nuclear PKC-beta labeling. PKC-alpha labeling in
      proliferating cells showed similar immunoreactivity in both control cytoplasm and
      nucleus. Treatment of proliferating cells with HuIFN alpha-2b for 2 min decreased
      PKC-alpha in the cytoplasm (59%) and nucleus (44%). In confluent cells,
      cytoplasmic PKC-alpha labeling decreased 59% at 1 min, 61% at 2 min, and 76% at
      10 min of HuIFN alpha-2b treatment. Nuclear PKC-alpha decreased by 65% at 1 min,
      80% at 2 min, and 62% at 10 min after HuIFN alpha-2b treatment. Western blots of
      total PKC-alpha in proliferating and confluent cells and PKC-beta in confluent
      cells showed similar results. However, Western blots of total PKC-alpha and -beta
      in proliferating cells did not demonstrate any significant changes in either PKC
      alpha or -beta immunoreactivity following 1-min HuIFN alpha-2b treatment. These
      results suggest that treatment of proliferating U-373 cells with HuIFN alpha-2b
      for 1 min unfolds and exposes PKC-beta antigenic sites (hinge region) and
      increases in situ PKC-beta immunogold labeling.

PMID- 8562474
TI  - Selective activation of protein kinase C isoforms by v-Src.
AB  - Protein kinase C (PKC) is a gene family consisting of no less than 11 distinct
      isoforms. In both murine and rat fibroblasts, we detected expression of four PKC
      isoforms: the conventional PKC alpha, the novel PKCs delta and epsilon, and the
      atypical PKC zeta. With the conventional and novel PKC isoforms, membrane
      association has been used to show PKC activation. In cells transformed by v-Src,
      there was a Ca(2+)-dependent increase in membrane association of the alpha
      isoform relative to the nontransformed parental cells. The zeta isoform had a
      slightly increased membrane association in murine fibroblasts transformed by v
      Src but not in rat fibroblasts transformed by v-Src. However, since it is not
      clear whether cellular distribution of zeta isoform correlates with activation,
      the data are inconclusive with regard to this isoform. Interestingly, of the
      Ca(2+)-independent PKC isoforms delta and epsilon, only the delta isoform was
      preferentially associated with membrane fractions in v-Src-transformed cells. The
      lack of PKC epsilon activation was not due to lack of responsiveness to
      diacylglycerol (DG), since exogenously supplied DG and phorbol ester were both
      able to induce membrane association of PKC epsilon. Thus, the differential
      activation of the delta and epsilon isoforms by v-Src suggests a more complex
      mechanism for the activation of the novel Ca(2+)-independent PKC isoforms,
      involving more than simply elevating DG levels. Since PKC has been implicated in
      the intracellular signals activated by v-Src that lead to transformation, the
      selective activation of PKC alpha and delta suggests a role in mitogenesis and
      transformation for these PKC isoforms.

PMID- 8562475
TI  - Apoptosis induced by protein kinase C inhibition in a neuroblastoma cell line.
AB  - The protein kinase C inhibitor bisindolylmaleimide GF109203X has a dual effect on
      the behavior of the neuroblastoma cell line Neuro-2A; when the inhibitor is added
      in conditions that induce differentiation (absence of serum), neurite outgrowth
      is potentiated in a dose-dependent manner. However, if the inhibitor is added in
      growth-promoting conditions (presence of serum), programmed cell death
      (apoptosis) is induced, as assessed by internucleosomal DNA cleavage and specific
      immunoassays. This effect is also seen with other specific protein kinase C
      inhibitors. Bcl2 gene overexpression protects Neuro-2A cells from apoptosis, as
      has been found in other systems. We also show that calpain I, a neutral Ca(2+)
      activated proteinase, participates in this apoptotic pathway. Our results point
      to a key role of protein kinase C in the regulation of growth and differentiation
      in Neuro-2A cells.

PMID- 8562476
TI  - Localization of protein kinase C isozymes in rat colon.
AB  - We have demonstrated previously the presence of classical (alpha), novel (delta
      and epsilon), and atypical (zeta) protein kinase C (PKC) isozymes in human and
      rat colonic mucosa (L. A. Davidson et al., Arch. Biochem. Biophys., 312:547-553,
      1994). To gain insight into the functions of individual PKC isozymes in colonic
      epithelium in situ, we determined the localization of the major PKC isozymes
      expressed in normal rat colonic epithelial cells using in situ reverse
      transcription (RT)-PCR and immunohistochemistry (IH). Cytokeratin, a positive
      biological control known to be expressed in epithelial cells, was shown by in
      situ RT-PCR and IH to be expressed only in epithelial cells within the colonic
      crypt. PKC gamma, a negative control for the colon since it is expressed only in
      the central nervous system, was not detectable in colon sections by either
      methodology. In situ RT-PCR analysis revealed that PKC alpha, delta, epsilon, and
      zeta mRNAs are expressed in epithelial cells along the entire colonic crypt. In
      addition, PKC delta and zeta mRNA are expressed in the stromal layer. All four
      PKC isozymes in the colonic epithelial cells were also detected by IH. However,
      in general, isozyme protein expression was greater at the top of the crypt axis,
      associated primarily with cells having acquired a differentiated phenotype. These
      results suggest that PKC isozyme protein expression may be localized to mature
      differentiated cells at the top of the colonic crypt. Therefore, PKC isozyme
      dependent signal transduction may play a role in colonic epithelial cell ontogeny
      along the colonic crypt axis.

PMID- 8562477
TI  - Expression of the RET oncogene induces differentiation of SK-N-BE neuroblastoma
      cells.
AB  - Expression of the RET proto-oncogene, a cell surface receptor for an as yet
      unknown ligand, is associated with tumors, tissues, and cell lines of neural
      crest origin. Accumulating evidence suggests that RET activity is involved in the
      process of neuronal differentiation. Moreover, induction of phenotypic
      differentiation of neuroblastoma cell lines is associated with the rapid
      accumulation of RET transcripts. To verify the role of RET in neuronal
      differentiation, we introduced into the human neuroblastoma cell line SK-N-BE
      four versions of the RET oncogene, activated by different mechanisms: RET/PTC1
      and RET/PTC3, which are activated by rearrangement with heterologous genes; and
      two activated RET mutants, which carry the single amino acid substitution found
      associated to the inheritance of the multiple endocrine neoplasia type 2A
      (retMEN2A allele) and type2B (retMEN2B allele), respectively. We demonstrate
      that, after transfection with the RET oncogenes, SK-N-BE cells display a reduced
      growth rate and acquire a neurite-bearing phenotype accompanied by enhanced
      expression of the axonal growth-associated protein, GAP-43, and the high
      molecular weight neurofilament, NF200. These results indicate that, when
      activated, RET is able to cause growth inhibition and to promote neuronal
      differentiation of neuroblastoma cells.

PMID- 8562478
TI  - Normal p53 status and function despite the development of drug resistance in
      human breast cancer cells.
AB  - Loss of or mutations in p53 protein have been shown to decrease both radio- and
      chemosensitivity. The present study assessed the p53 gene status, ability to
      arrest in G1 of the cell cycle, the functionality of the p53 transduction
      pathway, and apoptosis following treatment with radiation in a series of drug
      resistant human breast cancer cells to determine whether p53 alterations occur
      during the development of drug resistance. We used 13 sublines derived from MCF
      7, ZR75B, and T47D cells, which were resistant to doxorubicin, paclitaxel,
      vinblastine, cisplatin, etoposide, and amsacrine. Eleven of 12 drug-resistant
      sublines retained the parental p53 gene status, as determined by sequence
      analysis and functional yeast assay; only one subline was found to have acquired
      a mutation in the p53 gene. The MCF-7 TH subline was found to both acquire
      mutated p53 and to have major changes in p53 protein expression and function. In
      12 other drug-resistant sublines, the G1 checkpoint was conserved or only
      slightly impaired. A normal accumulation of p53, p21Cip1/Waf1, and Mdm2 proteins
      and hypophosphorylation of Rb protein occurred in response to radiation with only
      small differences noted in the kinetics of p53 and p21Cip1/Waf1 induction.
      Increased susceptibility to apoptosis was found in the ZR75B drug-resistant
      sublines, whereas no evidence for apoptosis was observed in the ZR75B, MCF-7, and
      T47D parentals and the MCF-7 and T47D drug-resistant sublines. This effect could
      not be explained by alterations in bcl-2 or bax expression. Our results
      demonstrate that alterations in: (a) p53 gene status; (b) ability to arrest in
      G1; (c) induction of p53 protein and p53-dependent genes; and (d) decreased
      activation of apoptosis is not a requirement for the onset of drug resistance.
      The function of p53 appears to be dissociated from drug resistance in our model
      system.

PMID- 8562479
TI  - Transfection of wild-type but not mutant p53 induces early monocytic
      differentiation in HL60 cells and increases their sensitivity to stress.
AB  - HL60 cells, which lack the p53 gene due to a deletion, were used as an in vitro
      model system to study the effect of wild-type p53 gene expression on
      hematopoietic differentiation. We transfected HL60 cells with wild-type p53 and
      two mutant p53 cDNAs encoding the Val to Ala mutation at codon 143 and the Arg to
      Trp mutation at codon 248. Flow cytometry, growth, and cytochemical analysis for
      alpha-napthyl butyrate esterase activity and nitroblue tetrazolium reduction
      indicated that wild-type p53 but not mutant p53 induced early monocytic
      differentiation in the transfected HL60 cells without terminal growth arrest. The
      wild-type p53 transfectants did not differentiate along the granulocytic pathway,
      even when induced with 1.25% DMSO for 6 days; rather, these cells resembled
      monocytic cells, confirming that wild-type p53 transfection caused these cells to
      become committed to differentiate along the monocytic pathway. HL60 cells
      transfected with wild-type p53 were more sensitive to stress, such as growth in
      serum-depleted medium and exposure to a chemotherapeutic agent, etoposide.

PMID- 8562480
TI  - Reversion of transformed phenotype of human adenocarcinoma A549 cells by
      expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase complementary DNA.
AB  - 3-Hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase) plays a rate
      limiting role in isoprenoid biosynthesis and is associated with cell
      proliferation and transformation. Although an elevated level of HMG-CoA reductase
      activity is consistently detected in cancer cell lines and tumors, the question
      remains whether HMG-CoA reductase activity may have a causative role in cell
      transformation. We have stably transfected the A549 human adenocarcinoma cells
      with both bicistronic and retroviral expression vectors, including the whole cDNA
      of human HMG-CoA reductase. Stably transfected cells showed strong morphological
      changes and disorganization in the filamentous actin architecture, became contact
      inhibited, and had a lower doubling time. Moreover, they exhibited anchorage
      independent growth reduction and lost their capability to induce tumors in nude
      mice. Surprisingly, no quantitative modification of enzyme activity was observed
      following transfection, although expression of HMG-CoA reductase cDNA was shown
      by Northern blot analysis. When endogenous and transfected reductase activity was
      bypassed by the addition of mevalonate and compactin, a competitive inhibitor,
      the filamentous actin distribution in HMG-CoA reductase-transfected cells became
      very similar to that of control cells, demonstrating the role of exogenous HMG
      CoA reductase activity in this process. All of our data together strongly suggest
      that phenotype reversion is dependent on exogenous HMG-CoA reductase expression
      and that enzymatic activity is implied in this mechanism. HMG-CoA reductase cDNA
      expression, by expression of a particular form of reductase, might be a negative
      regulator of cell growth and thus reverse the phenotype of tumor cells.

PMID- 8562481
TI  - Mitogenic signaling by transfected neuromedin B receptors in Rat-1 cells.
AB  - The rat neuromedin B (NMB) receptor was expressed in Rat-1 fibroblasts to
      elucidate the signaling pathways and mitogenic effects mediated by this seven
      transmembrane domain receptor. Receptor expression was verified by ligand binding
      and Ca2+ mobilization, which were blocked by the NMB receptor antagonist D-Nal
      Cys-Tyr-D-Trp-Orn-Val-Cys-Nal-NH2. NMB acted as a potent growth factor promoting
      DNA synthesis and cell proliferation in serum-free medium in Rat-1 cells
      transfected with the NMB receptor. Prior to DNA synthesis, NMB stimulated
      phosphorylation of 80K/MARCKS, a major substrate of protein kinase C, which could
      be prevented by the selective protein kinase C inhibitor GF 109203X. Furthermore,
      NMB induced a rapid p42MAPK activation and tyrosine phosphorylation of multiple
      proteins including p125FAK and paxillin. The half-maximal concentrations (EC50)
      of NMB required to induce DNA synthesis (0.7-0.9 nM) and cell proliferation (0.7
      1 nM) paralleled the Kd for 125I-[D-Tyr0]NMB binding and the EC50 values for the
      induction of the early signaling events. Thus, NMB can activate multiple signal
      transduction pathways and act as a sole mitogen through its receptor expressed in
      Rat-1 fibroblasts.

PMID- 8562482
TI  - jun-NH2-terminal kinase activation mediated by UV-induced DNA lesions in melanoma
      and fibroblast cells.
AB  - jun-NH2-terminal kinase (JNK) belongs to a family of protein kinases that
      phosphorylates c-Jun, ATF2, and Elk1 in response to various forms of stress
      including UV irradiation and heat shock. Although in previous studies we have
      demonstrated the importance of membrane components for JNK activation by UV
      irradiation, here we have elucidated the role of DNA damage in this response. We
      show that in vitro-irradiated or sonicated DNA that is added to proteins prepared
      from UV-treated cells can further induce JNK activation in a dose-dependent
      manner. When compared with UV-B (300 nm), UV-C (254 nm), which is better absorbed
      by the DNA, is significantly more potent in activating JNK. Furthermore, when
      wavelengths lower than 300 nm were filtered out, UV-B was no longer able to
      activate JNK. With the aid of melanoma and fibroblast cells, which exhibit
      different resistances to irradiation and require different UV doses to generate
      the same number of DNA lesions, we demonstrate that above a threshold level of
      0.45 lesions and up to 0.75 lesions per 1875 bp, the degree of JNK activation
      correlates with the amount of lesions induced by UV-C irradiation. Finally, to
      explore the role of nuclear and mitochondrial DNA (mtDNA) in mediating JNK
      activation after UV irradiation, we have used cells that lacks mtDNA. Although
      the lack of mtDNA did not impair the ability of UV to activate JNK, when
      enucleated, these cells had lost the ability to activate JNK in response to UV
      irradiation. Overall, our results suggest that DNA damage in the nuclear
      compartment is an essential component that acts in concert with membrane-anchored
      proteins to mediate c-Jun phosphorylation by JNK.

PMID- 8562483
TI  - Activation of the epidermal growth factor receptor by skin tumor promoters and in
      skin tumors from SENCAR mice.
AB  - The present study was designed to further investigate the role of the epidermal
      growth factor receptor (EGFr) in mouse skin tumor promotion by evaluating the
      status of the EGFr in tumor promoter-treated mouse epidermis and in mouse skin
      tumors. Female SENCAR mice received three topical treatments of either the
      phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) or the nonphorbol esters
      okadaic acid and chrysarobin. Membrane proteins from SENCAR mouse epidermis were
      isolated 6 h after the last treatment, and the phosphotyrosine content of the
      EGFr and several potential substrates were examined by Western blot analysis. The
      results indicated that multiple applications of all three tumor promoters led to
      an increase in the phosphotyrosine content of the EGFr and also of several lower
      molecular weight proteins (M(r) approximately 80,000-85,000). Phosphorylation of
      PLC gamma 1 on tyrosine residues could not be detected in tumor promoter-treated
      mouse epidermis when the phosphotyrosine content of the EGFr was elevated or in
      cultured keratinocytes exposed to exogenous EGF. When two tyrosine kinase
      inhibitors (tyrphostins RG50864 and RG13022) were incorporated into the treatment
      regimens, the TPA-induced epidermal hyperplasia and cell proliferation were
      effectively blocked, and the TPA-stimulated EGFr tyrosine phosphorylation was
      significantly reduced. Examination of the phosphotyrosine content of epidermal
      membrane proteins isolated from skin papillomas revealed that the EGFr also had
      elevated phosphotyrosine levels. These results demonstrate that multiple topical
      treatments with both phorbol ester and nonphorbol ester tumor promoters lead to
      activation of the EGFr tyrosine kinase in mouse epidermis. In addition, these
      data suggest that signaling through the EGFr pathway plays an important role in
      the tumor promotion stage of multistage carcinogenesis in mouse skin.

PMID- 8562484
TI  - Norepinephrine stimulates the expression of fibroblast growth factor 2 in rat
      brown adipocyte primary culture.
AB  - To elucidate the role of norepinephrine (NE) in the hyperplasia of brown adipose
      tissue (BAT), we investigated the effects of NE on the expression of fibroblast
      growth factor-2 (FGF-2) in rat brown adipocyte primary culture and on capillary
      growth in an in vitro angiogenesis model in which microvascular fragments and
      brown adipocyte precursor cells isolated from rat BAT were grown in coculture. NE
      significantly increased the number of brown adipocyte precursor cells. The NE
      effect on cell proliferation was greatly inhibited by anti-FGF-2-specific
      antibody. Likewise,NE considerably increased the levels of FGF-2 mRNA and the
      antigen in brown adipocyte primary culture. The ability of NE to stimulate the
      expression of FGF-2 mRNA was blocked by actinomycin D or was inhibited partly by
      propranolol. Moreover, NE considerably increased the in vitro capillary growth
      and the level of FGF-2 antigen in the coculture. These results suggest that NE is
      a crucial factor to mediate FGF-2 production, in part via the beta-adrenergic
      receptor, in rat brown adipocytes and to stimulate the cell proliferation and
      capillary growth in BAT by an autocrine/paracrine mechanism.

PMID- 8562485
TI  - Modulation of retinoblastoma and retinoblastoma-related proteins in regenerating
      rat liver and primary hepatocytes.
AB  - Protein expression of the retinoblastoma (Rb) tumor suppressor gene product was
      examined by immunoblot analysis of nuclei isolated from regenerating rat liver
      after 70% partial hepatectomy (PH). Levels were almost undetectable in quiescent
      0-h livers but increased 15- to 60-fold 3 to 24 h post-PH, 105-fold at 30 h, and
      20- to 50-fold at 60 to 72 h post-PH. Expression returned to near baseline levels
      at 18, 42, and 48 h post-PH. A similar pattern of Rb protein expression in the
      regenerating liver was observed by indirect immunofluorescence microscopy, with
      peak nuclear expression at 30 h post-PH. Rb-related proteins with apparent
      molecular masses of 300, 156, and 74 kDa were detected in regenerating liver
      using mAbs to the Rb protein. Their expression increased 6- to 8-fold during
      regeneration, and only p156 returned to baseline levels at 60 h post-PH. Rb and
      its related proteins were detected in cultured primary hepatocytes, and although
      total protein levels did not change appreciably, there was a dramatic shift from
      cytosol into nuclei through 96 h. The half-life of the Rb protein was determined
      to be 1.9 h in regenerating liver and 2.2 h in cultured primary hepatocytes. Rb
      protein abundance in synchronized HuH-7 human hepatoma cells was cell cycle
      dependent and exhibited peak nuclear expression during S phase. Rb protein was
      detected primarily in its hyperphosphorylated state during liver regeneration and
      through the cell cycle of the HuH-7 cells. In vivo administration of transforming
      growth factor beta 1, an inhibitor of DNA synthesis in regenerating liver,
      resulted in reduced expression of Rb as well as its protein partners, cell cycle
      dependent kinase 4 and cyclin E. The results suggest that in the regenerating rat
      liver and in synchronized HuH-7 cells, expression of Rb protein is modulated in a
      cell cycle-dependent fashion, remains primarily in a hyperphosphorylated state,
      and exhibits a relatively short half-life. The inhibition of Rb protein
      expression by transforming growth factor beta 1 may be linked to its simultaneous
      suppression of cell cycle-dependent kinase 4 and cyclin E protein levels.

PMID- 8562486
TI  - The tuberous sclerosis 2 gene is expressed at high levels in the cerebellum and
      developing spinal cord.
AB  - Tuberous sclerosis (TS) is an autosomal dominant multisystem disorder
      characterized by the widespread development of hamartomas in many tissues and
      organs. TSC2 is predicted to encode a 1784-amino acid tumor suppressor protein
      that may function, in part, as a GTPase-activating protein for Rap1. Given the
      high incidence of central nervous system abnormalities in individuals affected
      with tuberous sclerosis, the expression of TSC2 in developing and adult nervous
      system tissues was examined. Reverse transcription-PCR, Northern blot, and in
      situ hybridization analyses demonstrated high levels of expression of TSC2 in the
      adult brain and developing central nervous system. Abundant TSC2 expression was
      detected in the adult cerebellum, hippocampus, and olfactory bulb, with lower
      levels of expression observed in other tissues, including heart and kidney. This
      enrichment of TSC2 expression in neurons in the central nervous system suggests
      unique roles for this tumor suppressor gene product in the development and
      differentiation of nervous system tissues.

PMID- 8562487
TI  - Growth imbalance and altered expression of cyclins B1, A, E, and D3 in MOLT-4
      cells synchronized in the cell cycle by inhibitors of DNA replication.
AB  - Expression of cyclins at the translational level is generally studied by
      immunoblotting lysates of cells synchronized in the cycle. Most methods used to
      synchronize transformed cells induce growth imbalance. The aim of the present
      study was to analyze levels of cyclins B1, A, E, and D3 in the respective phases
      of the cycle in synchronized human leukemic MOLT-4 cells, correlate them with
      total cellular protein content (reflecting growth imbalance), and compare the
      synchronized cells with cells from unperturbed, asynchronous cultures. Expression
      of cyclins detected immunocytochemically in individual permeabilized cells was
      analyzed by multiparameter flow cytometry, which made it possible to relate
      position of the cell in the cell cycle with cyclin expression. Cells synchronized
      at the G1-S boundary by thymidine, mimosine, or aphidicolin had about 40%
      increased total protein and 4-5 fold higher levels of cyclins E and B1 compared
      to their G1 counterparts from unperturbed cultures. Expression of cyclin A in
      synchronized cells was 2-fold higher, while expression of cyclin D3 was
      essentially unaltered. The synchronized cells traversing S phase after release
      from the block had elevated but decreasing levels of cyclins E, B1, and A.
      Although the cyclin expression of cells reentering G1 was similar to that of
      their counterparts from asynchronous cultures, the total protein content was
      still elevated by about 30%. The data indicate that due to different degrees of
      imbalance in total protein and individual cyclin content, levels of cyclins
      detected by immunoblotting of cell lysates from synchronized cultures may not be
      representative of their expression in unperturbed cells. The elevated level of
      cyclin B1 in the cells arrested at the G1-S boundary may reflect the increased
      half-life of this protein, stabilized as the result of the overexpression of
      cyclin E.

PMID- 8562488
TI  - A continuum of psychosis, one human gene, and not much else--the case for
      homogeneity.
AB  - The contention of this paper is that psychoses are not a collection of separate
      and unrelated diseases, but a set of diverse expressions of a single underlying
      entity. It will be argued that there is a basic homogeneity of pathogenesis, that
      there are not multiple predisposing genes but a single gene that is associated
      with significant diversity. Therefore the problem is a unitary one. The challenge
      is to identify the nature and function of the gene. It will be argued that the
      gene is that by which homo sapiens has separated from other primate species, and
      that the diversity arises from selective pressures which continue to act on this
      specifically human gene.

PMID- 8562489
TI  - A case against subtyping in schizophrenia.
AB  - In this paper we consider the generally accepted view that schizophrenia is
      'heterogeneous'. We point out that the view derives from prima facie evidence
      from clinical presentation, studies of course, and factor analysis. However, upon
      closer examination internal contradictions are apparent, e.g., subtypes change,
      different groupings of symptoms cooccur in the same individual. Another type of
      paradigm, depending on careful study of case controls (e.g., monozygotic twins
      discordant for schizophrenia) and distributions, indicates that abnormalities in
      neurocognition, regional cerebral blood flow, and regional neuroanatomy may be
      present in nearly every patient, irrespective of absolute level or diagnostic
      subtype. These results suggest that a simple model in which patients vary along a
      severity dimension might parsimoniously explain much of the variance. Thus, while
      it is possible and even probable that schizophrenia may have many etiologies,
      phenocopies may represent the expression of a unitary pathogenesis of greater or
      lesser impact.

PMID- 8562490
TI  - The case for or against heterogeneity in the etiology of schizophrenia. The
      genetic evidence.

PMID- 8562491
TI  - The case for heterogeneity in the etiology of schizophrenia.
AB  - To confirm etiological heterogeneity, it is required that schizophrenic patients
      may be separated into at least two classes having different known etiologies and,
      perhaps, different pathophysiological signatures. In contrast, the homogeneity
      hypothesis asserts that there is a single necessary and sufficient cause or
      configuration of causes of schizophrenia. Because the link between phenotypic
      heterogeneity and etiological heterogeneity is tenuous, attempts to use purely
      phenotypic data to infer etiologic heterogeneity must be viewed cautiously. We
      examined three candidate causes for schizophrenia: genes, obstetric complications
      and viral infection. Cytogenetic studies show that some rare cases of
      schizophrenia are due to gross abnormalities of chromosomes. As for the large
      majority of schizophrenic patients, the candidate cause data most certainly
      reject the most parsimonious version of the hypothesis of etiological
      homogeneity: that all schizophrenia is caused by exactly the same pattern of
      genetic mutations, birth related complications and exposure to the same viral
      infections. We conclude that the heterogeneity debate should consider the
      possibility of rewording the question: 'Heterogeneity: yes or no?' to
      'Heterogeneity: how much?'

PMID- 8562492
TI  - Variability in BPRS definitions of positive and negative symptoms.
AB  - Reviewing Brief Psychiatric Rating Scale (BPRS) research indicates that combining
      items to form larger 'symptom factors' (e.g., depression, psychosis) has become
      the standard methodology. Unfortunately, a single symptom factor may be defined
      by different combinations of different BPRS items in different studies. To
      examine the potential impact of these differences, a number of different BPRS
      definitions of positive and negative symptoms in schizophrenia were culled from
      previous research. To compare these definitions, one hundred schizophrenics were
      interviewed with regard to current and recent symptomatology and rated on the
      BPRS, the Schedule for the Assessment of Negative Symptoms (SANS), and the
      Schedule for the Assessment of Positive Symptoms (SAPS). The four BPRS negative
      symptom definitions all correlated highly with one another and with the SANS.
      There were no differences in the amount that these different definitions of
      negative symptoms correlated with the SANS. Also, the nine definitions of
      positive symptoms all correlated highly with one another and with the SAPS.
      However, there were significant differences in how they correlated with the SAPS.
      Because of these differences, possible standard definitions for negative and
      positive symptoms of schizophrenia are proposed for future use of the BPRS in
      research.

PMID- 8562493
TI  - Negative symptoms in schizophrenia: their evolution during an acute phase.
AB  - Whereas the instability of positive symptoms over time is well recognized, the
      instability of negative symptoms is still debated. This controversy could be due
      to the fact that different negative symptoms have been studied in different
      phases of schizophrenia. We, therefore, hypothesized that some negative symptoms
      would improve whereas others would remain perfectly stable during the remission
      of the acute phase of illness. We further hypothesized that the changes in these
      negative symptoms would be linked to changes in other domains such as
      extrapyramidal, depressive and positive symptomatology. A broadly defined sample
      of schizophrenic patients was evaluated at admission and discharge of the
      hospital with the Scale for the Assessment of Negative Symptoms (SANS) and the
      Scale for the Assessment of Positive Symptoms (SAPS), the Montgomery and Asberg
      Depression Rating Scale (MADRS) and the Extrapyramidal Symptoms Rating Scale
      (ESRS). Doses of antipsychotic medications were converted into chlorpromazine
      equivalents. Fifty-seven patients (mean age 40.3 years old) were included in the
      sample and followed-up during their hospitalization. All the sub-scores of the
      SANS-SAPS decreased significantly but 4 items of the SANS belonging to the
      affective flattening subscale (unchanging facial expression, decreased
      spontaneous movements, paucity of expressive gestures and lack of vocal
      inflections) and one item belonging to the alogia subscale (poverty of speech)
      did not vary significantly, showing the necessity of taking into account the
      individual items of the SANS rather than the subscale scores to evaluate the
      course of negative symptoms. Changes in all the SANS subscores except the alogia
      subscore were associated with variations in scores of other scales. The change in
      attentional subscores was positively correlated to the change in the positive
      formal thought disorder subscores, probably because both belong to the same
      syndrome. The change in affective flattening subscores was associated with
      changes in depressive and akinetic scores and 28% of the variance of the change
      in the affective flattening subscores was explained by the change in the MADRS
      scores. Changes in avolition-apathy and anhedonia subscores were also associated
      with changes in MADRS scores but not with the change in akinesia scores.

PMID- 8562494
TI  - Olfactory deficits in schizophrenia are not a function of task complexity.
AB  - The purpose of the current study was to determine if olfactory identification
      deficits in patients with schizophrenia were related to task complexity. Given
      that we had previously reported that male patients with schizophrenia are the
      most impaired on olfactory identification tests (the University of Pennsylvania
      Smell Identification Test, UPSIT), we wished to determine whether a similar
      deficit would exist for this group on a task of similar format and complexity,
      the Colour Identification Test (CIT). Sixty-five neuroleptically medicated
      patients with a DSM-III-R diagnosis of schizophrenia and 30 normal control
      subjects participated. The dependent measures were scores on the UPSIT and CIT.
      Overall, patients with schizophrenia had significantly lower USPIT scores than
      did the normal control subjects whereas no mean difference was observed for
      colour identification. Male patients with schizophrenia had olfactory
      identification deficits but performed comparably to all other groups on the CIT.
      Furthermore, microsmic patients with schizophrenia had CIT scores that did not
      differ from normal control subjects. Finally, CIT and UPSIT scores were not
      significantly correlated for the study sample as a whole. The results of this
      study suggest that the olfactory identification deficits observed in patients
      with schizophrenia likely reflect abnormalities of brain areas involved in
      olfactory pathways and are not a function of task complexity.

PMID- 8562495
TI  - Transient fluctuations in cognitive functioning in schizophrenia based on single
      case study methods.
AB  - The stability of cognitive performance in four schizophrenia patients was
      examined over a short time period. A cognitive battery highly sensitive to
      organismic state (the Repeatable Cognitive-Perceptual-Motor Battery, RCPM) was
      utilized. Single-case statistical methods tested for within-individual change
      across five assessments at two week intervals. All four subjects showed
      statistically significant post-baseline variation in a global measure of
      impairment (average impairment rating score) and in at least 50% of the
      individual tests having adequate test-retest reliability. Data are interpreted as
      providing suggestive evidence of transient fluctuations in performance within a
      stable window of impaired cognitive functioning. These fluctuations appear
      substantial enough to influence both research and clinical outcomes. The benefits
      of the single-case methodology employed are discussed. The data suggest that
      significant transient fluctuations in cognitive performance can be observed in
      schizophrenia in domains purported to represent vulnerability markers of the
      disorder. The importance of accounting for these transient fluctuations in the
      attempt to identify enduring, trait-like characteristics of cognitive functioning
      in schizophrenia is discussed.

PMID- 8562496
TI  - Smooth pursuit eye movement differences between familial and non-familial
      schizophrenia.
AB  - Disrupted smooth pursuit eye tracking characterizes a greater proportion of
      individuals with schizophrenia than in the normal population. The finding of a
      similar increased incidence of eye tracking abnormality in first degree relatives
      of schizophrenics implicates this disorder as a potential biological marker for
      schizophrenia. To test the assumption that the eye tracking dysfunction of
      schizophrenics is genetically related, left and right smooth pursuit gain and
      phase shift were compared between 20 schizophrenics with a family history of
      schizophrenia or schizophrenia-related disorders, 18 schizophrenics without a
      family history, as well as for 18 normal controls. Subjects tracked pendular
      targets on an LED light bar moving at frequencies of 0.2 and 0.7 Hz. Horizontal
      eye movements were recorded using DC-electro-oculography. Results indicate that
      schizophrenics with a positive family history had significantly reduced right
      pursuit gain compared with controls, while right gain for negative family history
      schizophrenics did not differ from either group. Schizophrenic subjects also were
      administered neuropsychological tests. Linear regression by groups analyses
      reveal that neuropsychological measures significantly predicted right gain to
      slower targets (0.2 Hz) for the positive family history schizophrenics, but not
      for negative family history schizophrenics.

PMID- 8562497
TI  - Reliability of post-mortem chart diagnoses of schizophrenia and dementia.
AB  - The reliability of psychiatric diagnosis has a direct effect on the validity of
      post-mortem analyses of neuropathological data, yet little is known about the
      reliability of retrospective diagnostic procedures which rely on review of
      medical records. In this paper, we report on the reliability of DSM-III-R
      psychiatric diagnoses assigned by a pool of 8 raters to a set of 106 state
      hospital charts of elderly, chronic patients who had died while institutionalized
      and were autopsied. Diagnoses were grouped by general diagnostic class, and Kappa
      coefficients computed for agreement among raters, as well as for agreement
      between ultimate consensus diagnoses and those made while subjects were living.
      Interrater agreement for those diagnoses that occurred most frequently in this
      sample (e.g. Schizophrenia and Dementia) was excellent, and comparable to the the
      agreement observed for ratings of live patients. Interrater agreement for less
      frequently occurring diagnoses (e.g. Mental Retardation, Mood Disorders, other
      non-Schizophrenic Psychoses) ranged from excellent to poor. We found high
      agreement between our rates diagnoses and those assigned by state hospital
      personnel while patients were living, although post-mortem review produced lower
      rates of diagnosis of both schizophrenia and Alzheimer-type dementias. Overall,
      results suggest that the reliability of chart review diagnosis is comparable to
      that obtained from interviews of live patients when experienced raters are used
      and diagnostic base rates are high enough to produce stable estimates of
      reliability.

PMID- 8562498
TI  - T cell activation by antigens on human melanoma cells--co-stimulation by B7-1 is
      neither sufficient nor necessary to stimulate IL-2 secretion by melanoma-specific
      T cell clones in vitro.
AB  - B7-1 expression, induced by transfection in poorly immunogenic murine tumours,
      was shown to elicit a T cell-mediated rejection of these tumours and further
      active immunity against the non-transfected tumour. We therefore asked to what
      level similarly induced expression of B7 on human melanoma cells would affect the
      antigen-dependent responses of tumour-specific T cell clones in vitro. Data
      presented show that B7-1 expression by melanoma lines: (i) significantly induced,
      or improved, an IL-2-dependent proliferative response of such clones to the
      antigen; (ii) increased the amount of IL-2 produced by two clones in response to
      the parental non-transfected tumour cells; and (iii) increased the TNF responses
      of all the CD4+ clones. However, despite these clear co-stimulatory effects on
      antigen-induced responses of all T cell clones, which demonstrated an effective
      interaction of the B7-1 transfected molecule with one or the other of its counter
      receptors expressed on T cell clones, B7 co-stimulation did not correct the
      defect of IL-2 secretion exhibited by many of these clones in response to in
      vitro antigen presentation by melanoma cells. We further show that defective IL-2
      secretion in response to melanoma antigens was not due to a T cell clone
      refractoriness induced by the culture, since one of these clones could be induced
      to secrete IL-2 by an antigen-expressing melanoma line, upon increased lymphocyte
      function associated antigen-3 expression induced by gene transfection. Together
      these data suggest that defective IL-2 secretion by many tumour-infiltrating
      lymphocytes clones in response to antigen presentation by melanoma cells in vitro
      is not exclusively due to the inability of these cells to provide an appropriate
      co-stimulation through the B7-1 molecule.

PMID- 8562499
TI  - Natural killer cell activity in lymphocytic choriomeningitis virus-infected beta
      2-microglobulin-deficient mice.
AB  - We have investigated the induction and role of natural killer (NK) activity in
      lymphocytic choriomeningitis virus (LCMV)-infected beta 2-microglobulin-deficient
      (beta 2m-) mice. We demonstrate that LCMV infection is more effective than
      polyinosinic:polycytidylic acid (poly I:C) at stimulating NK activity in beta 2m-
      mice. In addition, beta 2m- NK cells respond poorly to in vitro treatment with IL
      12. The target specificity of the virally induced NK cells is similar to that
      previously reported for chemically induced beta 2m- NK cells. In both cases they
      can lyse YAC-1 tumor cells but are unable to kill beta 2m- or beta 2m+ T cell
      blasts. We have also found that the time course of induction of NK and cytotoxic
      T lymphocyte (CTL) activity by LCMV in beta 2m- mice is delayed compared with
      normal mice. Maximal NK and CTL activity is attained at day 8 and 10 post
      infection respectively in beta 2m- mice compared with day 4 and 6-8 in B6 mice.
      Whereas normal mice die approximately 7 days following intracranial infection
      with LCMV, the course of disease in beta 2m- mice is protracted and characterized
      by a marked loss of body weight. We show that although the CD4+ CTL response in
      these mice is intimately involved in mediating weight loss, the virus-induced NK
      cells do not appear to play a role in the disease.

PMID- 8562500
TI  - Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and
      platelet P-selectin.
AB  - P-selectin is a Ca(2+)-dependent lectin that participates in leukocyte adhesion
      to vascular endothelium and platelets. Myeloid cells and a subset of T
      lymphocytes express carbohydrate ligands at the cell surface. Previously, we
      suggested that heat stable antigen (HSA/mouse CD24), an extensively glycosylated
      cell surface molecule on many mouse cells, is a ligand for P-selectin. Here we
      show that HSA mediates the binding of monocytic cells and neutrophils to P
      selectin. The monocytic cell lines ESb-MP and J774, peritoneal exudate cells, and
      bone marrow neutrophils could bind to lipopolysaccharide-activated bend3
      endothelioma cells under rotation-induced shear forces and this binding was
      inhibited by mAb to P-selectin and HSA. Blocking was weak at room temperature but
      more efficient at 4 degrees C when integrin-mediated binding was decreased. Also
      the adhesion of neutrophils to stimulated platelets expressing P-selectin was
      blocked by HSA- and P-selectin-specific mAb. Latex beads coated with purified HSA
      from myeloid cells bound to activated endothelioma cells or platelets, and the
      binding was similarly blocked by mAb to P-selectin and HSA respectively. The HSA
      coated beads were stained with P-selectin-IgG, very weakly with L-selectin-IgG
      but not with E-selectin-IgG. The staining was dependent on divalent cations and
      treatment with endoglycosidase F or neuraminidase indicated that sialylated N
      linked glycans were recognized. The presence of these glycans was confirmed by
      biosynthetic labeling studies. Our data suggest that HSA, in addition to the
      recently identified 160 kDa glycoprotein ligand on mouse neutrophils, belongs to
      a group of monospecific P-selectin ligands on myeloid cells.

PMID- 8562501
TI  - Virgin alpha beta and gamma delta T cells recirculate extensively through
      peripheral tissues and skin during normal development of the fetal immune system.
AB  - Current models of T cell migration place severe restrictions on the recirculation
      of virgin T cells, condemning them to migrate exclusively via high endothelial
      venules in lymph nodes until they either die or acquire the capacity to migrate
      to skin and peripheral tissues as memory cells following stimulation with
      antigen. We have demonstrated in the sheep fetus (which is immunologically virgin
      until after birth) that virgin T cells and dendritic cells circulate through skin
      and peripheral tissues during fetal life in the same non-random manner as adult T
      cells but in much larger numbers than they do in adult animals. Our data also
      showed that T cells do not discriminate between peripheral tissues and skin or
      lymph nodes on the basis of virgin or memory CD45R phenotype, or CD2, CD58 or
      CD44 phenotype, and with the possible exception of CD11a/CD18, that it is not
      mandatory for lymphocytes to be activated to adhesion moleculehi status in order
      to home to fetal skin. Our results indicate that unique tissue-homing
      specificities for extra-lymphoid tissues can be imprinted on virgin T cells
      independent of foreign antigen. Virgin T cells have previously been thought to be
      denied access to peripheral tissues; however, the large-scale traffic of virgin T
      cells through extra-lymphoid tissues in the fetus reported here provides a
      mechanism whereby direct virgin T cell interactions with self-antigens expressed
      only on tissues outside the thymus can occur repeatedly during development of the
      fetal immune system.

PMID- 8562502
TI  - alpha 2-Macroglobulin binds to and inhibits mannose-binding protein-associated
      serine protease.
AB  - We determined the presence in human serum of a complex consisting of mannose
      binding protein (MBP), MBP-associated serine protease (MASP), which is a C1s-like
      protein with complement activation activity, and alpha 2-macroglobulin (alpha
      2M). Binding between these three molecules was in an ascending order of MBP, MASP
      and alpha 2M, in that alpha 2M bound directly to MASP, possibly through covalent
      bonds, whereas the binding between MBP and MASP was reversible and Ca(2+)
      dependent. Since it was found that alpha 2M can inhibit complement activation by
      MASP and that MASP in the complex lacks esterolytic activity, it is conceivable
      that alpha 2M plays a regulatory role in MBP-derived complement activation via a
      mechanism involving MASP (the lectin pathway).

PMID- 8562503
TI  - Evidence for invariant chain 85-101 (CLIP) binding in the antigen binding site of
      MHC class II molecules.
AB  - The region of invariant chain encompassing residues 81-104 is critical for
      association with MHC class II molecules. This segment of invariant chain, termed
      CLIP for Class II-associated invariant chain Peptides, has been shown to inhibit
      antigenic peptide binding and T cell stimulation. Polymorphism affects the
      ability of CLIP to inhibit antigenic peptide binding, suggesting that CLIP may
      occupy the MHC II antigen binding site directly. However, CLIP may also mediate
      inhibition by binding to an alternate site causing an allosteric change to
      prevent antigenic peptide binding. The relationship between the apparent
      dissociation constant in the presence of a competitor (Kapp) and the competitor
      concentration can be examined to determine the nature of competition between two
      ligands. In competitive binding experiments between CLIP and antigenic peptide we
      find a linear dependence of Kapp on competitor concentration. These data are
      consistent with CLIP and antigenic peptide competing for the same site on the MHC
      class II molecule, thus arguing against an allosteric mechanism of CLIP
      inhibition. Mildly acidic conditions are thought to promote peptide loading in
      the endosome compartment by facilitating CLIP dissociation and enhancing
      antigenic peptide association. We have compared the effect of acidic pH on the
      equilibrium binding of murine CLIP and antigenic peptide to MHC class II
      molecules. Like antigenic peptide, CLIP binding can be greatly enhanced at mildly
      acidic pH, suggesting that a passive competitive mechanism for CLIP removal may
      not be sufficient to achieve loading of antigenic peptide in the endosome.

PMID- 8562504
TI  - The induction of human T cell unresponsiveness by soluble anti-CD3 mAb requires T
      cell activation.
AB  - In order to obtain an in vitro model of human T cell unresponsiveness induced by
      soluble anti-CD3 mAb in the presence of accessory cells, T cells purified from
      peripheral blood of healthy volunteers were cultured for 4 days with irradiated
      accessory cells and OKT3. After a 48 h resting period allowing TCR-CD3 complex re
      expression, T cells were rechallenged with plastic-immobilized OKT3, and their
      proliferative response as well as their secretion of IL-2, IFN-gamma and IL-10
      measured. Primary culture with OKT3 induced a state of unresponsiveness
      characterized by defective responses to OKT3 rechallenge but normal or enhanced
      responses to PMA and A23187 calcium ionophore, indicating a defect in the early
      steps of TCR-CD3-mediated signal transduction. Indeed, we found that unresponsive
      T cells displayed an impaired mobilization of intracellular calcium stores upon
      TCR-CD3 ligation. In order to determine whether the development of
      unresponsiveness depends on the initial T cell activation triggered by OKT3, we
      compared several versions of OKT3 differing in their ability to bind Fc
      receptors. We found that only the activating antibodies that bind Fc receptors on
      accessory cells induced T cell unresponsiveness. We conclude that human resting T
      cells can be rendered unresponsive by anti-CD3 mAb in soluble form provided that
      they trigger T cell activation.

PMID- 8562505
TI  - A mAb against HLA-A2 can be influenced both positively and negatively by the
      associated peptide.
AB  - Presentation of peptides by class I HLA molecules is essential for the
      development of a T cell-mediated immune response. TCRs have the ability to
      discriminate among large numbers of different HLA-peptide complexes. We have
      identified a mAb, MA2.1, that also discriminates among HLA-A2 associated with
      different peptides. A soluble form of HLA-A2 bound to single peptides was
      prepared and its serological reactivity was studied using four mAbs. Three
      antibodies, W6/32, BB7.2 and BBM.1, recognized all the complexes equally. MA2.1,
      however, recognized most of the complexes equally but showed markedly different
      reactivity to two peptides bound to HLA-A2. MA2.1 recognized HLA-A2 complexed
      with the HIV-1 p17 epitope (SLYNTVATL) at least 30 times more strongly than all
      other complexes studied and this enhanced reactivity was found to be sensitive to
      a point mutation of threonine to alanine at position 8 in the peptide. In
      addition, MA2.1 had a very low reactivity for HLA-A2 complexed with the peptide
      TLWVDPYEV. Previous studies have mapped the binding epitope of MA2.1 to the alpha
      1 and alpha 2 helices of HLA-A2, suggesting two possible explanations for the
      ability of the bound peptide to influence MA2.1 reactivity. Either MA2.1 is
      sensitive to peptide-induced conformational changes of the helices, or it
      directly contacts certain peptides in the groove of HLA-A2.

PMID- 8562506
TI  - Rapid turnover of the recirculating lymphocyte pool in vivo.
AB  - Lymphocytes are unique among blood cells in their capacity to continually
      recirculate between blood and the tissues via the lymph. Previous estimates of
      lymphocyte lifespan in vivo and the turnover of the recirculating lymphocyte pool
      have been deduced from indirect labeling techniques. Using the fluorescent dye
      PKH-26, individual labeled cells have been tracked in sheep for periods > 2
      months. By direct measurement their lifespan was calculated. This label was found
      to be stable in vivo, allowing long-term analysis of the characteristics of the
      recirculating lymphocyte pool. It is possible to calculate the rate of turnover
      of cells of the recirculating pool based on the rate at which labeled cells
      disappear from the lymphatic circulation. The recirculating lymphocyte pool was
      found to repopulate itself every 16.5 +/- 3.0 days. Using this label, it was
      estimated that recirculating lymphocytes divide on average once every 29.8 +/-
      6.8 days. Labeled erythrocytes were also examined and found to have an average
      lifespan of 153 days, demonstrating no dye loss over the 2 month period of
      observation. These data suggest that the recirculating lymphocyte pool is a
      highly dynamic compartment, with a high rate of turnover and peripheral cell
      division in vivo. This is the first report of the direct measurement of the in
      vivo turnover of recirculating lymphocyte pools, and this method may now be used
      to further analyze the lifespan of individual lymphocyte subsets and the in vivo
      lifespan of other cell types in vivo.

PMID- 8562507
TI  - The immune response and the eye. TCR alpha-chain related molecules regulate the
      systemic immunity to antigen presented in the eye.
AB  - Injection of antigen into the anterior chamber (AC) of the eye results in the
      induction of immune deviation in which antibody production is activated and
      delayed-type hypersensitivity (DTH) is inhibited. This system is termed anterior
      chamber associated immune deviation (ACAID) and the model is used to examine
      certain aspects of the immunologic privilege of the eye. Recent studies have
      established that following antigen presentation in the eye, an 'ACAID-inducing'
      signal is produced that directly enters the blood. This signal then homes to the
      spleen where T cells that down-regulate DTH are activated. For many antigens this
      'ACAID signal' is a soluble protein released within 2 days of AC injection.
      Although the presence of this molecule (or molecules) has been described using
      several antigens, the exact nature of the soluble mediator has escaped
      characterization. We have further explored the nature of this signal using HSV-1
      induced immune deviation. Our results show the soluble 'signal' was released by T
      cells that encounter antigen in the ocular microenvironment. This mediator was
      antigen specific, contained TCR alpha-chain (but not the TCR beta-chain)
      determinants and had an apparent molecular weight of 46 kDa. These results show
      that the release of soluble TCR alpha-chain from sites of T cell interaction
      within the microenvironment of the eye can regulate systemic immune responses.
      These results have implications for the control of immune response that might be
      damaging to organs such as the eye.

PMID- 8562508
TI  - Transcriptional regulation of the murine TCR zeta gene.
AB  - The TCR zeta chain plays a significant role in the assembly of the receptor
      complex and in coupling antigen recognition to the intracellular signal
      transduction apparatus. Since the zeta protein level is considered the limiting
      factor for receptor assembly in mature T cells, aberrant expression of the zeta
      chain affects both receptor structure and function. To understand the regulatory
      mechanisms controlling zeta gene expression, we characterized the 5' flanking
      region of the gene. Our analysis reveals the existence of at least three regions
      within the -784 to +121 fragment involved in the transcription of the zeta gene
      in T cells: (i) the fragment from -216 to +121 contains the basal promoter; (ii)
      the sequence between -561 and -216 includes positive elements which confer strong
      transcriptional activity; and (iii) the region between -784 and -561 which
      contains negative element(s) that down-regulate zeta gene transcription. The
      entire 5' flanking region of the zeta gene is functional in both T and fibroblast
      cell lines, although the transcriptional levels and the specific regions required
      for maximal activity differ between the two cell types. Maximal transcriptional
      activity is achieved when T cells are stimulated simultaneously via the TCR and
      with PMA. The transcriptional activity of the zeta gene can be induced by PMA
      alone in T cells but not in fibroblasts, suggesting that this effect is mediated
      by T cell-specific factors. We also demonstrate that upregulation of the
      transcriptional activity induced by the different stimuli is consistent with
      increased expression of zeta mRNAm, pointing to the possibility that signal
      transduction events initiated during T cell activation may be involved in
      controlling zeta gene expression.

PMID- 8562509
TI  - Generation of normal lymphocytes derived from N-myc-deficient embryonic stem
      cells.
AB  - Myc family proteins are thought to be transcription factors involved in
      regulation of cell growth and differentiation. N-myc is expressed at the pre-B
      cell stage of B cell differentiation and is dramatically induced by the pre-B
      cell growth factor, IL-7. To test the idea that N-myc plays an important role in
      lymphocyte development, we assayed the effect of a null N-myc mutation on the
      differentiation of B and T lineage cells. Homozygous, mutant embryonic stem (ES)
      cells were injected into blastocysts derived from recombination activating gene
      (RAG-2)-deficient mice. Since RAG-2 mutant mice fail to develop mature
      lymphocytes, later-stage lymphocytes that are present in chimeric mice are ES
      cell derived. Surprisingly, nearly normal numbers of mature T and B cells derived
      from N-myc-deficient ES cells were found in peripheral lymphoid organs of
      chimeric mice. Lymphocytes were judged to be functional based on responses to
      mitogens and production of serum IgM and multiple IgG isotypes in chimeric
      animals. We discuss these findings in relation to N-myc function in lymphocyte
      development and possible redundancy with other myc genes.

PMID- 8562510
TI  - Administration of IL-12 during ongoing immune responses fails to permanently
      suppress and can even enhance the synthesis of antigen-specific IgE.
AB  - The synthesis of antibodies of the IgE isotype in mice largely depends on IL-4, a
      cytokine that is released by T lymphocytes of the Th2 subtype. IL-12 is a
      cytokine considered to direct Th cell development into a Th1 direction and to
      suppress Th2 responses including the synthesis of IgE. Here we report about the
      influence of IL-12 on the IgE responses of mice immunized with protein antigens
      adsorbed to aluminum hydroxide. To avoid problems with the detection of IgE
      caused by an excess of competitive IgG antibodies produced in IL-12-treated mice,
      serum IgE was first extracted from the serum by plate-bound anti-IgE mAb and then
      determined either as total IgE or as antigen-specific IgE by using biotinylated
      anti-IgE or biotinylated antigen. Depending on the strain of mice and the dose of
      IL-12 injected together with the antigen, IL-12 can either temporarily suppress
      or augment the synthesis of (antigen-specific) IgE antibodies. This applies for
      CBA/J mice immunized six times in biweekly intervals with minute (0.1
      micrograms/injection) or three-times with large (5 micrograms/injection) amounts
      of the bee venom allergen phospholipase A2 (PLA2). Under both conditions the
      antibody response is characterized by the production of predominantly IgG1 as
      well as IgE but very little IgG2a, IgG2b and IgG3 antibodies. Simultaneous
      application of low doses of IL-12 (1 or 10 ng/day) led to a 2- to 4-fold
      enhancement of IgE production (PLA2-specific IgE or total IgE). Only a high dose
      of 1 micrograms IL-12/day resulted in a 3- to 10-fold reduction of the IgE
      response. This suppression was not stable, however, because the synthesis of IgE
      antibodies was stimulated to a high level when these mice subsequently received a
      second course of immunizations in the absence of IL-12. Likewise, the synthesis
      of IgE was only temporarily suppressed by IL-12 treatment in CBA/J mice immunized
      with keyhole limpet hemocyanin (KLH) as antigen. However, application of low (10
      ng/day) or high (1 microgram/day) doses of IL-12 during the primary course of
      immunizations of CBA/J mice with KLH suppressed the IgE response slightly or
      strongly respectively. In striking contrast, the KLH-specific IgE response of
      BALB/c mice was upregulated even when high doses of IL-12 (1 microgram/day) were
      injected simultaneously with the immunizations. Thus, these results demonstrate a
      great variability regarding the influence of IL-12 treatment on ongoing IgE
      responses in vivo.

PMID- 8562511
TI  - Expression of genes encoding the pre-TCR and CD3 complex during thymus
      development.
AB  - The mature TCR is composed of a clonotypic heterodimer (alpha beta or gamma
      delta) associated with the invariant CD3 components (gamma, delta, epsilon and
      zeta). There is now considerable evidence that more immature forms of the TCR-CD3
      complex (consisting of either CD3 alone or CD3 associated with a heterodimer of
      TCR beta and pre-T alpha) can be expressed at the cell surface on early
      thymocytes. These pre-TCR complexes are believed to be necessary for the ordered
      progression of early T cell development. We have analyzed in detail the
      expression of both the pre-TCR and CD3 complex at various stages of adult thymus
      development. Our data indicate that all CD3 components are already expressed at
      the mRNA level by the earliest identifiable (CD4lo) thymic precursor. In
      contrast, genes encoding the pre-TCR complex (pre-T alpha and fully rearranged
      TCR beta) are first expressed at the CD44loCD25+CD4-CD8- stage. Detectable
      surface expression of both CD3 and TCR beta are delayed relative to expression of
      the corresponding genes, suggesting the existence of other (as yet unidentified)
      components of the pre-TCR complex.

PMID- 8562513
TI  - Identification of an Mhc-DPB1 allele involved in susceptibility to experimental
      autoimmune encephalomyelitis in rhesus macaques.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an inducible autoimmune
      disorder that in rodents is known to be influenced by genetic background,
      specifically the Mhc class II region. Immunization of a group of outbred rhesus
      macaques with bovine high homogenate results in induction of the disease in
      approximately 65% of the animals. No clear association between the Mamu-DR or -DQ
      subregion of the rhesus macaque MHC (MhcMamu) and susceptibility or resistance to
      the disease has been documented. In this communication we describe a CD4+ Th cell
      line, isolated from an animal diagnosed with EAE, which proliferated in response
      to purified bovine myelin basic protein (MBP), a major constituent of the myelin
      sheath surrounding nerve cells. More specifically it only recognized a peptide
      including residues 61-82 of the molecule. Analysis of the T cell receptor (Tcr)
      usage of this MBP reactive T cell line showed functional transcripts for only two
      members of the V alpha 1 and one of each of the V beta 3 and V beta 6 families.
      The antigen-specific proliferative response was inhibited by a mAb reactive with
      MHC-DP molecules. Molecular analysis of the Mamu-DP region, in concert with
      allogeneic antigen presentation studies, demonstrated that the Mamu-DPB1*01 gene
      product functions as the restriction element for MBP peptide presentation.
      Retrospective analyses showed that this particular allele is frequently found in
      the group of EAE susceptible animals but is absent in the resistant animals (P <
      0.01). As a consequence, the Mamu-DPB1*01 allele may represent one of the risk
      factors involved in determining susceptibility to EAE in an outbred population of
      rhesus macaques.

PMID- 8562512
TI  - Cross-linking of Fc gamma receptors activates HIV-1 long terminal repeat-driven
      transcription in human monocytes.
AB  - Elevation of the levels of circulating immune complexes frequently accompanies
      HIV-1 infection and is a prognostic indicator of clinical progression from
      asymptomatic infection to AIDS. Here we report that cross-linking of Fc gamma RI
      or Fc gamma RII by adherent human IgG or by specific anti-Fc gamma R mAb
      activates HIV-1 gene expression in the human monocytic cell line BF24 and
      increased HIV RNA expression in monocytes from HIV infected patients as assayed
      by reverse transcription-PCR. In THP-1 cells, Fc gamma R cross-linking induced NF
      kappa B, which is known to bind to the regulatory region of the long terminal
      repeat (LTR) of HIV-1 and to activate HIV-1 transcription. Anti-TNF-alpha
      antibody but not anti-IL-1 beta antibody strongly inhibited both the induction of
      HIV-1-LTR-driven transcription and the induction of NF-kappa B by Fc gamma R
      cross-linking. These results indicate that Fc gamma R can mediate a TNF-alpha
      dependent induction of HIV-1 gene transcription and suggest that immune complexes
      may contribute to the pathophysiology of HIV-1 infection by augmenting viral
      replication in monocytes.

PMID- 8562514
TI  - Human thymic epithelial cells produce TGF-beta 3 and express TGF-beta receptors.
AB  - TGF-beta affects proliferation, differentiation and maturation of T cells;
      however, the effect of TGF-beta on thymic stromal cells has not been
      characterized. To better understand the role of TGF-beta in T cell development,
      we determined whether TGF-beta is present in the human thymus, and identified
      stromal cells that express TGF-beta receptors and respond to TGF-beta. We
      demonstrate that primary cultured human thymic epithelial cells (TEC) express TGF
      beta 1, TGF-beta 2 and TGF-beta 3, as well as TGF-beta type I receptor (T beta
      RI) (ALK-5) and TGF-beta type II receptor (T beta RII) transcripts. In vitro,
      epidermal growth factor (EGF) increases transcript levels of TGF-beta 1, TGF-beta
      3 and T beta RII, suggesting that EGF may modulate TGF-beta responses in TEC;
      however, TGF-beta 2 and T beta RI transcript levels were not affected. We also
      detect TGF-beta 3 and T beta RII protein in association with keratin-positive TEC
      in vitro and in vivo. TEC culture supernatants contain TGF-beta 3 as detected by
      Western blots and, upon heat and acid activation, display growth inhibitory
      activity on the CCL-64 cells that is neutralized by anti-TGF-beta mAb treatment.
      We further demonstrate that TGF-beta 1 increases leukemia inhibitory factor
      transcript levels in TEC, indicating that TEC express functional TGF-beta
      receptors. Thus, we have shown in the human thymus that TEC produce TGF-beta 3
      and express T beta RI and T beta RII. The data suggest that TGF-beta is present
      in the human thymus and may indirectly affect T cell development by regulating
      TEC cytokine production.

PMID- 8562515
TI  - ICAM-1 is required for T cell proliferation but not for anergy or apoptosis
      induced by Staphylococcus aureus enterotoxin B in vivo.
AB  - The response of T lymphocytes to superantigens requires expression of the
      appropriate TCR V beta gene products as well as the establishment of cellular
      interactions mediated by adhesion molecules. To study the role of intercellular
      adhesion molecule (ICAM)-1 in the response in vivo to superantigens, we have
      analyzed the effects induced by the bacterial superantigen Staphylococcus aureus
      enterotoxin B (SEB) in mice which have been made genetically deficient in ICAM-1.
      SEB treatment of wild-type mice causes proliferation, deletion and anergy of the
      SEB-reactive V beta 8+ T cell population. Here we show that cellular interactions
      mediated by ICAM-1 are not essential for the induction of anergy or for the
      deletion of CD4+ V beta 8+ or CD8+ V beta 8+ T cells, but are required for the
      proliferation of these peripheral T lymphocytes. This is the first demonstration
      in vivo that the absence of the co-stimulatory signals provided by the
      interaction of ICAM-1 with its specific ligands impairs the proliferation of SEB
      reactive T cells. Interestingly, our study showed that SEB-induced proliferation
      of CD8+ V beta 8+ T cells from lymph nodes (not from spleen) is independent of
      the interactions mediated by ICAM-1.

PMID- 8562516
TI  - Disposable devices for the dispensing of oral drops. Study of photoprotectiveness
      and compatibility.
AB  - Amber-coloured syringes designed for the distribution of unit-doses of oral drops
      were studied for the efficiency of the photoprotectiveness and the possible
      binding of eleven phenothiazine neuroleptics: alimemazine, chlorpromazine,
      cyamemazine, fluphenazine, levomepromazine, periciazine, pipotiazine,
      prochlorperazine, thioproperazine, thioridazine, and trifluoperazine, all very
      easily oxidized in solution in daylight. Spectrofluorimetry made it possible, in
      one operation, to determine the remaining concentrations of drugs after storage
      and to verify the absence of photo-oxidation. The storage was performed up to 13
      days at 25 +/- 3 degrees C and without any precaution from daylight. All the
      drugs studied were stable and none bound on the syringes. However, the stability
      appeared to be due to the antioxidants in the drug preparations, and not to the
      coloured material, since oral drops were also stable in uncoloured syringes
      designed for injection. Nevertheless, the amber-coloured syringes efficiently
      protect the active principles in pure aqueous solutions, without preservative,
      and thus this physical protection reinforces the chemical one of the galenical
      formulation.

PMID- 8562517
TI  - Microcapsules obtained from complex coacervation of collagen and chondroitin
      sulfate.
AB  - Microcapsules composed of collagen and chondroitin sulfate were obtained by
      complex coacervation and characterized by DSC, optical microscopy, SEM, and UV
      Vis spectroscopy. Composition of the microcapsules could be adjusted by the feed
      ratio and the pH of the solution. Prepared under low temperature and aqueous
      solution, the process is most suitable for encapsulating delicate bioactive
      agents. Albumin as a model protein was encapsulated with a loading level of up to
      95% by weight. Degradation rate of the microcapsules decreased with the
      concentration of the crosslinking agent glutaraldehyde and increased with the
      bacterial collagenase level. Correspondingly the release of albumin could also be
      varied by the cross-linking degree of the microcapsules.

PMID- 8562518
TI  - Theoretical modelling of plasma protein adsorption/desorption processes onto
      solid surfaces.
AB  - Experimental data from particle electrophoretic measurements of polymer particles
      have been used for modelling competitive protein adsorption. It could be
      demonstrated that protein adsorption onto a solid surface is a two-step process:
      firstly fast reversible adsorption and, secondly, irreversible coupling at the
      adsorption centres dependent on contact time. The extent of protein competition
      is influenced by a characteristic time-dependence of the adsorption process.
      Analysis of the experimental findings results in two models whose corresponding
      systems of kinetic equations were solved. Both suggested models are based upon
      relatively simple mechanisms: (a) the parallel reaction; and (b) the exchange
      reaction. It has been shown that in our experiments a classical exchange process
      for describing competitive protein adsorption can be very probably supposed.

PMID- 8562519
TI  - Effects of Tween 20 on the desorption of proteins from polymer surfaces.
AB  - The effects of Tween 20 on the desorption of proteins from polyethylene and
      polyurethane were studied, using single protein solutions of the human proteins
      fibrinogen (Fb), immunoglobulin G (IgG), serum albumin (HSA), high density
      lipoproteins (HDL), and plasma. The surfactant may partly or even completely
      desorb the proteins, depending on the type of polymer and protein. About 40% of
      adsorbed HSA and 80% of adsorbed HDL from the corresponding single protein
      solutions were desorbed by Tween 20 from polyethylene, whereas Tween 20 had a
      small effect on the desorption of adsorbed Fb and IgG under the same conditions.
      However, the desorption of Fb and IgG by Tween 20 was much higher in the case of
      a diluted plasma solution compared to a pure protein solution. These findings may
      be explained by the differences of the interaction strengths between polymers and
      the adsorbed proteins. The displacement of HSA from polyethylene by Tween 20
      occurred in the first few minutes and did not increase in time. It was also
      observed that preadsorbed Tween 20 was able to prevent in a large extent the
      adsorption of HSA onto polyethylene. Thus, the effect of Tween 20 on the
      desorption of protein is due to either the displacement of protein or prevention
      of protein adsorption onto the surfaces.

PMID- 8562520
TI  - Effect of toluene extraction on Biomer surface: II. An atomic force microscopy
      study.
AB  - The surface characterization of Biomer and extracted Biomer has been investigated
      using atomic force microscopy (AFM) in order to show the influence of extraction
      process on the morphology and local interactions which monitor surface properties
      at a molecular scale. The high viscoelasticity of these polymers provided by the
      soft segments makes AFM imaging in contact mode quite difficult, the scanning of
      the tip inducing artifacts on the surface. The rate, direction, and number of
      scans strongly influence this friction effect. The recording of force curves has
      shown that the extraction and conditions of drying can modify the interaction
      forces present at the polymer surface. Imaging of the extracted Biomer obtained
      with AFM in non-contact mode has revealed inclusion nodules embedded in an
      amorphous phase. This may be attributed to the migration at the surface of the
      non-eliminated poly(aminomethacrylate) additive.

PMID- 8562521
TI  - Protein adsorption on low temperature isotropic carbon: V. How is it related to
      its blood compatibility?
AB  - Based on our research on blood protein interactions with low temperature
      isotropic carbon (LTIC) and data from the literature, we propose that the carbon
      surface has strong interactions with adsorbed proteins. In this paper we focus on
      how a relatively blood-compatible material interacts with plasma proteins. We
      present our results on the structure and properties of the LTIC surface utilizing
      SEM, STM, XPS, and contact angle measurements. We briefly review protein
      adsorption on LTIC using DSC, impedance, radioisotopes, and two-dimensional gel
      electrophoresis. LTIC is characterized by a microporous, oxidized, hydrophobic,
      and domain mosaic structure. Surface polishing smoothens the roughness and
      removes the porosity, while largely destroying the ordered atomic texture, making
      the surface more random and more amorphous. The LTIC surface denatures all
      adsorbed proteins studied. The rate of protein adsorption is high and the surface
      concentration is large. The LTIC surface adsorbs all proteins without preference.
      The surface also tenaciously retains proteins such that they cannot be displaced
      by buffer or exchanged by proteins in solution. We conclude that LTIC
      accomplishes its blood compatibility through a passivating film of strongly
      adsorbed bland proteins, which do not interact with platelets nor participate in
      blood coagulation. We also suggest mechanisms for the production of such a film
      by the LTIC surface.

PMID- 8562522
TI  - Poly(vinyl chloride) formulations: acute toxicity to cultured human cell lines.
AB  - Two quantitative cytotoxicity assay methods (cytoplasmic retention of
      carboxyfluorescein and mitochondrial cleavage of 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT)) have been used to evaluate the response of
      two cultured human cell lines; HepG2 (hepatoma) and W138va13 (transformed lung
      fibroblasts) to extracts of a range of poly(vinyl chloride) (PVC) formulations.
      Two plasticizers; di(2-ethylhexyl)phthalate (DEHP) and di-isooctyl phthalate and
      a range of tin and non-tin stabilizers were incorporated in the study. Only those
      formulations containing both a plasticizer and a tin-based stabilizer produced
      extracts which were toxic. Extracts of those formulations which contained both
      plasticizer and dibutyl tin dimaleate stabilizer were toxic to both cell lines in
      both assay methods. Extracts of a formulation containing plasticizer and a
      dioctyl tin mercaptide were toxic to both cell lines in the carboxyfluorescein
      assay but were only toxic to the WI38va13 cells in the MTT assay. The WI38va13
      cells were generally more sensitive to the extracts than the HepG2 cells. When
      serial dilutions of the extracts were evaluated, the carboxyfluorescein assay
      proved to be the more sensitive of the two. The acute toxicity of extracts of
      these PVC formulations cannot be directly attributed to the plasticizers or to
      the tin stabilizers. It is likely that a synergistic mechanism, such as
      plasticizer facilitated extraction of the tin stabilizer, exists.

PMID- 8562523
TI  - Jacob Markowitz Award.

PMID- 8562524
TI  - The changing face of surgical research: from tissue repair to gene replacement.

PMID- 8562525
TI  - Developments in dental and maxillofacial surgical research.

PMID- 8562527
TI  - Future trends for experimental surgery in laboratory animal science.

PMID- 8562526
TI  - Experimental surgery: where are we going?

PMID- 8562528
TI  - The role of the surgeon scientist in gene therapy.

PMID- 8562529
TI  - Evaluation of CMC and HA solutions for adhesiolysis.
AB  - Aqueous hyaluronic acid (HA) and carboxymethylcellulose (CMC) solutions were
      tested as tissue-protective coatings during lysis of surgical adhesions by blunt
      dissection or electrocautery in a rat cecal abrasion model. Phosphate-buffered
      saline (PBS) was used as a tissue coating solution in 200 female Sprague-Dawley
      rats prior to controlled cecal abrasion with a surgical gauze-tipped rotary
      abrader (four 1.5-cm-diameter areas; 70 g weight/60 revolutions/130 rpm). One
      week after this initial cecal abrasion, rats were operated on again and adhesions
      were scored and lysed. The rats were randomly assigned to receive experimental
      tissue coating solutions either before (prelysis; n = 160) or after (postlysis; n
      = 40) adhesiolysis. Animals with prelysis coatings were further divided into
      blunt dissection or electrocautery adhesiolysis groups and were tested with 2 mL
      cecal coating of PBS, 0.4% HA, 0.5% CMC, or 1.0% CMC tissue coating solutions (n
      = 20/group). Rats treated postlysis received 2 mL cecal coating plus 2 mL
      intraperitoneal instillation of PBS, 1.8, 1.9, or 2.0% CMC. One week after
      adhesiolysis, rats were operated on again for final adhesion scoring. Prelysis
      tissue coating with 0.5 or 1.0% CMC solution appeared to inhibit adhesion
      reformation after blunt dissection, whereas 0.4% HA was not effective in this
      model. Solutions applied before electrocautery dissection or after blunt
      dissection were ineffective.

PMID- 8562530
TI  - The rat as an animal model for total hip replacement arthroplasty.
AB  - Dogs, goats, and sheep are the most commonly used animals in studies of total hip
      replacement (THR) arthroplasty. However, the development of a small, laboratory
      animal model could have significant economic and housing advantages over these
      models when studying the long-term systemic effects of chronic mechanically
      functional implants. A THR was designed and fabricated with a cobalt-alloy (F-75)
      femoral and UHMWPE acetabular component for PMMA-cemented implantation in the
      rat. Mature Sprague-Dawley rats (n = 18) were maintained at a constant weight
      (450 g) and were trained to walk on a low-speed (6 m/min), horizontal treadmill,
      15 min/day, 5 days/week. Each animal was randomly assigned to one of three
      surgical groups: functional, nonfunctional, and sham. The functional and
      nonfunctional groups underwent identical procedures, except that in the
      nonfunctional group the femoral head was placed so as to prevent articulation
      with the socket in the acetabular component. The sham procedure consisted of
      exposing and opening the joint capsule and the iliac wing without luxating the
      femoral head or severing the ligamentum teres. In addition, half of the animals
      in each group resumed exercising on the treadmill at 1 week after surgery. The
      implants were recovered at 2 months after surgery. The results show that the
      surgical procedure is feasible in the rat, the postoperative recovery was typical
      of that for THR, and the rats were able to resume their exercising regimens.
      Radiographic evaluation revealed that the majority of the sham and the
      nonfunctional animals had luxated hips, while the majority of the functional
      animals had reduced hips. Histological results were typical of THR in other
      species. The success of the surgical model suggests that the rat may be a
      feasible, reduced-cost alternative to other lab species in systemic, long-term
      THR studies.

PMID- 8562531
TI  - Reduction of hepatic reperfusion injury by indomethacin-mediated
      vasoconstriction: a rat model with temporary splenocaval shunt.
AB  - For reduction of radical formation during reperfusion, a lower oxygen supply by
      limiting the reperfusion flow rate should be beneficial for the organ. Thus,
      indomethacin was given prior to reperfusion for induction of temporary
      postischemic vasoconstriction. In an in vivo model (female Wistar rats, 200-250
      g, n = 16) with portal decompression by a splenocaval shunt, hepatic ischemia was
      induced for 30 min by cross-clamping of the hepatoduodenal ligament followed by
      portal intravenous injection of indomethacin (2 mg/kg body wt) at the end of
      ischemia. Liver injury was assessed by serum levels of Aspartat-aminotransferase
      (ASAT) and Alaninaminotransferase (ALAT) that were determined prior to ischemia,
      on days 2, 4, 6 and 21 postoperatively. The local tissue pO2 was measured
      preischemically, 1 h after reperfusion and on day 21. Application of indomethacin
      significantly reduced the local tissue-pO2 by about 50% after 1 h of reperfusion
      (p < .05). The increase in serum ASAT levels on day 2 was significantly
      diminished after indomethacin application (p < .05). ALAT values on day 2 showed
      a significant increase in the control group but did not differ from baseline in
      the indomethacin group. These data support the hypothesis that temporarily
      limited reperfusion results in an amelioration of reperfusion injury, although
      further studies with more selectively vasoactive agents must still be performed
      since indomethacin also has a major effect on the eicosanoid metabolism.

PMID- 8562532
TI  - Catheterization of the subarachnoid space in rabbits using a Vascular Access
      Port.
AB  - A surgical technique allowing chronic access to the subarachnoid space in
      unanesthetized rabbits was devised using the Vascular Access Port system.
      Instrumentation provides the investigator with a method of measuring intracranial
      pressure and sampling cerebrospinal fluid in awake rabbits. The catheter is
      introduced into the dorsal cervical subarachnoid space at the C4-C5
      intervertebral space via dorsal laminectomy and passed cranially into the
      cisterna magna. The access port is subcutaneously implanted in the dorsal
      thoracic region between the scapulas. This system reduces the potential for
      infection, is not easily removed by the animal, and is relatively easy to access
      with minimal discomfort for the animal.

PMID- 8562533
TI  - Anterior patch aortic aneurysm model for the study of endoluminal grafts.
AB  - Endovascular graft repair for aortic aneurysms has led to concerns regarding the
      healing characteristics of the graft within a thrombus-lined aneurysm and the
      effect that collateral flow may have on the endoluminal prosthesis and the
      aneurysm. An anterior aortic patch aneurysm model that preserved collateral
      arteries was examined and modified to address these issues. In canines (n = 30) a
      Dacron knitted patch (n = 27) or a rectus fascia patch (n = 3) was sutured into a
      3.5-cm anterior aorotomy. Dacron patch aneurysm diameter was an average of 21.8
      +/- 2.2 mm (mean canine normal aortic diameter 9.06 +/- 0.79 mm). Canines
      underwent angiogram, computed tomography, and/or intravascular ultrasound from 1
      to 11 weeks later, at which time an endoluminal prosthesis was deployed and
      followed 30 to 60 days until harvest. Aneurysms accumulated minimal thrombus
      through the initial 11 weeks. Significant stenosis (mean 21.2% +/- 19%) occurred
      at aneurysm necks in association with a patch imbrication suture technique (n =
      11). Following modification (n = 16), this decreased to a mean of 3.6 +/- 9.7%.
      Collateral lumbar artery patency was 95% at the time of imaging prior to graft
      placement. Following successful graft implantation, 16 of 18 aneurysms were
      filled with thrombus and in most cases the collateral circulation occluded. One
      of three fascial patch aneurysms ruptured 21 days after creation. This model more
      accurately depicts abdominal aortic aneurysms with the inherent thrombus and
      collateral flow that is important when studying aspects of endovascular aortic
      graft repair.

PMID- 8562534
TI  - Preschool visual screening.

PMID- 8562535
TI  - Topical aldose reductase inhibitor.

PMID- 8562536
TI  - Cytomegalovirus retinitis: are intraocular devices the answer?

PMID- 8562537
TI  - Assessment of an inner city visual screening programme for preschool children.
AB  - AIMS: The efficiency of preschool visual screening programmes to detect amblyopia
      is questionable. In this study such a programme in an inner city was assessed to
      determine its effectiveness. METHODS: The results of screening and hospital
      treatment of 712 patients who were considered to require referral were entered
      into a database for analysis. Default rates were assessed and the efficacy of
      treatment determined. RESULTS: The only effective screening test for the
      detection of amblyopia was visual acuity. A large proportion of referred patients
      had refractive problems only. High default rates, particularly in geographical
      areas of lower socioeconomic grading, severely handicapped any attempt to reduce
      the incidence of amblyopia. CONCLUSION: A fresh approach to the detection and
      care of amblyopia in the inner city community is required, perhaps by performing
      screening of children in their first year of attendance at school to reduce
      default rates. Cycloplegic refraction of children who are found to have reduced
      visual acuity before their referral to hospital is also recommended.

PMID- 8562538
TI  - Topical aldose reductase inhibitor for correcting corneal endothelial changes in
      diabetic patients.
AB  - BACKGROUND: Marked variations in cell size (polymegethism) and shape
      (pleomorphism) are characteristic of the corneal endothelium in diabetic patients
      and animals. METHOD: Wide field specular microscopy was used to evaluate the
      clinical efficacy of treating the diabetic corneal endothelium with topical
      instillation of 0.5% aldose reductase inhibitor, CT-112. RESULTS: Morphological
      variations (polymegethism and pleomorphism) of the endothelium in eight eyes from
      eight patients receiving CT-112 resolved within 3 months after initiation of
      treatment. In contrast, no change in endothelial morphology was noted in five
      eyes from five patients who received placebo. CONCLUSION: These observations
      suggest that aldose reductase may be involved in the aetiology of corneal
      endothelial variations in diabetic patients.

PMID- 8562539
TI  - Acanthamoeba keratitis: risk factors and outcome.
AB  - AIMS/BACKGROUND: This study was initiated to investigate risk factors for and
      outcome of Acanthamoeba keratitis. METHODS: Results of treatment were studied in
      22 patients (23 eyes) presenting to Bristol Eye Hospital between 1985 and
      February 1995. Details related to the use and disinfection of contact lenses were
      also obtained. An additional two patients who were seen at Bristol but mainly
      treated elsewhere were surveyed for contact lens related information only.
      RESULTS: The incidence of Acanthamoeba keratitis rose substantially in the 1990s:
      three patients presented before 1990, while the remaining 21 presented between
      January 1990 and February 1995. Eleven patients have presented since january
      1994. All of the patients in this series were contact lens wearers, 16 (67%)
      using daily wear disposable contact lenses. Contact lens disinfection data were
      available in 22 patients of whom 11 (50%) were using chlorine disinfectant. Other
      types of disinfection were much less common. Four patients (18%) had not used any
      disinfectant. During the course of the series the average diagnostic delay has
      fallen markedly, although in 77% of patients a diagnosis of a viral keratitis,
      most commonly herpes simplex, was made on first presentation. All but three of
      the series were treated with a combination of polyhexamethylene biguanide and
      propamidine isethionate. Penetrating keratoplasty was performed in 9/23 eyes
      (39%); in all of these eyes diagnosis was delayed for at least 6 weeks. All but
      one of the eyes in the series achieved a visual acuity of 6/9 or better after
      treatment, and 18 eyes (78%) saw 6/6 or better. CONCLUSIONS: Most patients with
      Acanthamoeba keratitis can now expect a good visual result and cure by medical
      therapy alone is favoured by early diagnosis.

PMID- 8562541
TI  - Optic nerve head circulation in untreated ocular hypertension.
AB  - AIMS: The laser Doppler technique was used to compare the capillary blood speed
      measured at localised sites of the optic nerve head in stable, untreated ocular
      hypertensive patients with that measured in healthy normal subjects. The
      stereophotogrammetric technique was also used to measure the retinal nerve fibre
      layer thickness at the disc margin in the eyes of the patients. METHODS: Doppler
      broadening measurements were made at superior and inferior temporal disc sites in
      18 eyes of 10 ocular hypertensive patients and in 12 eyes of seven age and sex
      matched normal subjects. RESULTS: On average, Doppler broadening and, hence,
      capillary blood speed were significantly higher (p = 0.018) in the patients than
      in the normal subjects. The largest values of Doppler broadening in the patients
      were measured at sites adjacent to the thinnest retinal nerve fibre layer. Linear
      regression analysis showed a significant inverse relation (p = 0.0004) between
      Doppler broadening and nerve fibre layer thickness in left eyes, and a nearly
      significant relation (p = 0.06) in right eyes. At temporal sites of the optic
      nerve head there is a compensatory relation between a thinning nerve fibre layer
      and a locally increasing blood supply to the optic nerve head. CONCLUSION:
      Together with previous observations of fluorescein filling defects in similar
      patients, these results indicate that there is spatial heterogeneity of blood
      flow in the optic nerve head in stable, untreated ocular hypertensive patients.

PMID- 8562540
TI  - Diode laser contact transscleral retinal photocoagulation: a clinical study.
AB  - AIM: To examine the clinical efficacy of contact transscleral retinal
      photocoagulation with a diode laser. METHODS: Transscleral retinal
      photocoagulation was performed on 36 eyes. The conditions treated included
      peripheral retinal breaks associated with retinal detachments (30 eyes) and giant
      retinal tears (six eyes). Of the 30 eyes with retinal detachments, 28 underwent
      transscleral photocoagulation to the site of drainage of subretinal fluid in an
      attempt to reduce the risk of hemorrhage. RESULTS: Threshold lesions were
      obtained with irradiances of between 95.4 W/cm2 and 191 W/cm2. Satisfactory
      chorioretinal adhesion was achieved in all eyes with retinal breaks and giant
      retinal tears. The only significant complications of treatment encountered were
      punctate choroidal haemorrhages (three eyes). Drainage related choroidal
      haemorrhage following earlier photocoagulation occurred in two of 28 eyes.
      CONCLUSIONS: This study confirms the clinical potential of transscleral diode
      laser photocoagulation in the therapy of surgical retinal conditions.

PMID- 8562542
TI  - Changes in intraocular pressure during low dose intravenous sedation with
      propofol before cataract surgery.
AB  - AIMS: This study examined the effects on intraocular pressure, pulse rate, and
      blood pressure of low dose intravenous sedation with propofol. METHODS: Twenty
      adult patients who were scheduled to undergo cataract surgery were given a single
      intravenous bolus (0.98 (SEM 0.4) mg/kg) of propofol for sedation before
      administering the local anaesthetic for cataract surgery. A small intravenous
      dose of lignocaine was the only other anaesthetic or sedative agent given. The
      intraocular pressure in the non-surgery eye, the pulse rate, and the blood
      pressure were measured before and after propofol induction. RESULTS: Compared
      with the preinduction baseline, there was a 17% to 27% (from 16.2 (0.7) mm Hg to
      11.8 (0.7) mm Hg) decrease in intraocular pressure after propofol induction. A
      significant decrease in intraocular pressure occurred within the first minute and
      was still evident at 7 minutes when the measurements were stopped. There was also
      a 7%-12% increase in pulse rate during the first 4 minutes, a 12% decrease in
      mean systolic blood pressure, and a 7% decrease in mean diastolic blood pressure
      from baseline after propofol induction. CONCLUSION: A single low dose bolus of
      propofol used for sedation before cataract surgery caused a moderate reduction in
      intraocular pressure with minimal, easily managed side effects.

PMID- 8562543
TI  - Long term effect of apraclonidine.
AB  - AIMS: To evaluate the effect of the chronic use of apraclonidine 0.5% on the
      intraocular pressure (IOP) of patients with glaucoma; also, to study the side
      effect profile of this drug when used chronically. METHODS: All patients who had
      uncontrolled IOP, who were either already on glaucoma medications, or who were
      intolerant of other glaucoma medications were enrolled. A total of 185 patients
      were started on apraclonidine 0.5% two to three times a day in one eye. RESULTS:
      Follow up extended to 35 weeks. The mean difference in IOP between treated and
      control eyes was 2.1 (SD 5.0) mm Hg. A similar IOP lowering effect was obtained
      comparing IOP difference from baseline in the treated eye only. CONCLUSION: By
      the end of the follow up period, 46% of patients were still on the medication.
      The drug was stopped in 23% of patients because of side effects and in 31% of
      patients because of failure to lower IOP significantly.

PMID- 8562544
TI  - Optic disc size and optic nerve damage in normal pressure glaucoma.
AB  - BACKGROUND: Recent reports indicate that eyes with normal pressure glaucoma have
      larger optic discs than eyes with primary open angle glaucoma or normal eyes.
      This study was performed to find whether, in normal pressure glaucoma, a large
      disc is associated with more optic nerve damage than a small disc. METHODS:
      Colour optic disc photographs of 74 patients with normal pressure glaucoma were
      assessed morphometrically. RESULTS: Taking the study group as a whole, the optic
      disc size decreased significantly (p = 0.04) with increasing visual field defect.
      In an intraindividual bilateral comparison, the side differences in the disc area
      of the right minus the left eye of the same individual were not significantly
      correlated with the side differences in the mean visual field defect.
      CONCLUSIONS: The results indicate that the eye with the larger optic disc, when
      compared with the contralateral eye with the smaller optic nerve head, showed
      neither a significantly more marked nor less pronounced glaucomatous optic nerve
      damage. It suggests that for a given patient the degree of glaucomatous optic
      nerve atrophy was not markedly associated with the optic disc size. The finding
      that patients with large visual field defects had smaller discs than patients
      with moderate perimetric loss may indicate that the results of previous cross
      sectional studies reporting on an unusually large disc size in normal pressure
      glaucoma may be due partially to selection.

PMID- 8562545
TI  - Use of perfluorocarbon liquids in proliferative vitreoretinopathy: results and
      complications.
AB  - BACKGROUND: The present study was set up to evaluate the influence of
      perfluorocarbon liquids on the postoperative anatomical and functional results as
      well as on the complication rates in eyes with proliferative vitreoretinopathy
      (PVR). METHODS: Sixty five consecutive eyes (64 patients) with PVR in different
      stages requiring surgical intervention where liquid perfluorocarbons were used
      were compared with 64 consecutive eyes (62 patients) operated without the help of
      perfluorocarbon immediately before this time. Both groups were similar with
      regard to severity of PVR, number of operations, and initial visual acuity. The
      observation period was shorter in the perfluorocarbon group because they were
      operated more recently (17.4 months as against 24.4 months). RESULTS: The
      anatomical as well as the functional success rates were not significantly higher
      in the perfluorocarbon group (69% v 61% and 65% v 53% respectively). However, in
      cases operated on without perfluorocarbons where reproliferation would occur it
      was of much greater severity than in cases where perfluorocarbons were used. The
      number of uncured cases with contraction of the retina at least in the inferior
      half was more than twice as high in the group operated on without
      perfluorocarbon. Combined with massive reproliferation secondary glaucoma and
      bullous or band keratopathy were more frequent in eyes treated before the use of
      perfluorocarbon. CONCLUSION: The intraoperative use of perfluorocarbon liquids in
      vitreoretinal surgery does not prevent postoperative reproliferation but does
      reduce its severity.

PMID- 8562546
TI  - Simultaneous bilateral cataract extraction in the UK.
AB  - AIMS/BACKGROUND: Simultaneous bilateral extracapsular cataract extraction (SBCE)
      is not routinely performed in the developed world. This study investigated the
      safety and efficacy of this procedure as performed in the UK. METHODS: A review
      of 319 consecutive patients (638 eyes) who underwent SBCE with posterior chamber
      intraocular lens implantation is presented. RESULTS: The incidence of
      intraoperative complications was 7.7%. These included posterior capsule rupture
      (0.8%) and vitreous loss (0.3%). Postoperative complications were seen in 8.7% of
      operated eyes and included iris prolapse (0.3%) and raised intraocular pressure
      (3.0%). Endophthalmitis occurred in one eye (0.15%). There were no major
      bilateral complications, and, in particular, no cases of bilateral
      endophthalmitis. Final visual acuities compared favourably with reports for
      unilateral surgery. Eighty two per cent achieved a final visual acuity of 6/12 or
      better, and 41% tested 6/6 or better. CONCLUSION: This study illustrates that
      SBCE is not associated with an increased incidence of complications and that the
      visual results are good. Where indicated, and under strict surgical protocol,
      this procedure is safe.

PMID- 8562547
TI  - Cataract patients in a defined Swedish population 1986-90: VII Inpatient and
      outpatient standardised mortality ratios.
AB  - AIMS: Cataract surgery has at times been said to correlate with an increased
      death risk. We have therefore analysed the standardised death ratio in a
      population based cohort of patients that had undergone cataract surgery. METHODS:
      Data for all patients undergoing cataract surgery from 1986 up to and including
      1990 in the Lund Health Care District were prospectively recorded, and 5120 were
      retrieved for analysis. Death dates and primary death diagnoses for each patient
      were obtained from the Swedish Bureau of Census up to and including 1991.
      Standardised mortality ratios were calculated for all patients, subdivided into a
      number of categories: inpatients, outpatients, sex, age < 75 years, age > or = 75
      years, patients with heart and circulatory diseases, with malignant tumours, and
      with diabetes. The cut off age was set at 74 because this divided the patients
      into two approximately equal groups. Using time dependent survival regression,
      the relative risk for dying were estimated for sex, age, and for postoperative
      YAG laser capsulotomy, and also for diabetic patients and patients with
      rheumatoid arthritis. RESULTS: Inpatients almost always show an increased
      standardised mortality ratio compared with outpatients. Young patients and
      diabetic patients also showed an increased standardised mortality ratio, compared
      with the normal population, but not older patients, who constitute the majority.
      Cardiovascular death diagnoses were overrepresented among the young. CONCLUSIONS:
      Cataract surgery is correlated with an increased standardised mortality ratio
      only in young patients and in patients with certain complicating diseases like
      diabetes and cardiovascular diseases.

PMID- 8562549
TI  - Analysis of glucose-6-phosphate dehydrogenase in anterior subcapsular and mixed
      cataractous lenses.
AB  - The study was undertaken to determine the different concentrations of glucose-6
      phosphate dehydrogenase (G-6-PD) in anterior subcapsular and mixed cataractous
      lenses. In both types of cataractous lenses an increased concentration of G-6-PD
      was observed in 41-50 year age groups and a lower concentration of G-6-PD was
      noted in 61 year and above age groups. Cataractous lenses of females have a
      higher content of G-6-PD than males. In anterior subcapsular cataractous lenses,
      a lower concentration of G-6-PD was noted than in mixed lenses.

PMID- 8562548
TI  - Diabetic retinopathy: morphometric analysis of basement membrane thickening of
      capillaries in different retinal layers within arterial and venous environments.
AB  - AIMS: To assess quantitatively variations in the extent of capillary basement
      membrane (BM) thickening between different retinal layers and within arterial and
      venous environments during diabetes. METHODS: One year after induction of
      experimental (streptozotocin) diabetes in rats, six diabetic animals together
      with six age-matched control animals were sacrificed and the retinas fixed for
      transmission electron microscopy (TEM). Blocks of retina straddling the major
      arteries and veins in the central retinal were dissected out, embedded in resin,
      and sectioned. Capillaries in close proximity to arteries or veins were
      designated as residing in either an arterial (AE) or a venous (VE) environment
      respectively, and the retinal layer in which each capillary was located was also
      noted. The thickness of the BM was then measured on an image analyser based two
      dimensional morphometric analysis system. RESULTS: In both diabetics and controls
      the AE capillaries had consistently thicker BMs than the VE capillaries. The BMs
      of both AE and VE capillaries from diabetics were thicker than those of
      capillaries in the corresponding retinal layer from the normal rats (p < or =
      0.005). Also, in normal AE and VE capillaries and diabetic AE capillaries the BM
      in the nerve fibre layer (NFL) was thicker than that in either the inner (IPL) or
      outer (OPL) plexiform layers (p < or = 0.001). However, in diabetic VE
      capillaries the BMs of capillaries in the NFL were thicker than those of
      capillaries in the IPL (p < or = 0.05) which, in turn, had thicker BMs than
      capillaries in the OPL (p < or = 0.005). CONCLUSIONS: The variation in the extent
      of capillary BM thickening between different retinal layers within AE and VE
      environments may be related to differences in levels of oxygen tension and
      oxidative stress in the retina around arteries compared with that around veins.

PMID- 8562550
TI  - Two dimensional mapping of the perfusion of the retina and optic nerve head.
AB  - AIM: To present a new non-invasive method of performing a high definition
      topography of perfused vessels of the retina and the optic nerve head with
      simultaneous evaluation of blood flow. METHOD: By a combination of a laser
      Doppler flowmeter with a scanning laser system the perfusion of the retina and
      the optic nerve head is visualised. The principles of measuring blood flow by
      laser Doppler flowmetry are based on the optical Doppler effect: laser light
      scattered by a moving particle is shifted in frequency by an amount delta f. Our
      data acquisition and evaluation system is a modified laser scanning tomograph.
      The technical data are retinal area of measurement 2.7 mm x 0.7 mm, 10 degrees
      field with 256 points x 64 lines, measurement accuracy 10 microns, wavelength 670
      nm and 790 nm, light power 100 microW and 200 microW, data acquisition time 2.048
      s. Every line is scanned 128 times by a line sampling rate of 4000 Hz. By
      performing a discrete fast Fourier transformation over 128 intensities of each
      retinal point the laser Doppler shift is calculated for each retinal point. With
      these data a two dimensional map with 256 x 64 points of the retinal perfusion is
      created. The brightness of the pixel is coded by the value of the Doppler shift.
      Offline capillary blood flow is estimated in arbitrary units according to the
      theory of laser Doppler flowmetry in every region of interest of the perfusion
      picture. We estimated the reliability and the validity of the method. Retinal
      blood flow was measured by scanning laser Doppler flowmetry (SLDF) while varying
      intraocular pressure by a suction cup of three healthy volunteers. Measurements
      of retinal blood flow performed in 47 eyes by the presented method (SLDF) were
      correlated with data gained by a commercially available laser Doppler flowmeter.
      Perfusion pictures of the superficial retinal layer and of deep prelaminar layers
      in the optic nerve head are presented. RESULTS: The reliability coefficients r1
      of 'flow', 'volume', and 'velocity' were 0.84, 0.85, and 0.84 respectively. We
      found a significant linear relation between SLDF flow and the ocular perfusion
      pressure (r = 0.84, p < 0.001). Comparative measurements of the retinal blood
      flow by SLDF and a commercially available laser Doppler flowmeter showed a linear
      and significant relation (flow r = 0.6, p < 0.0001, volume r = 0.4, p < 0.01).
      Capillaries of the retinal superficial vasculature or deep ciliary sourced
      capillaries of the optic nerve head became visible with a high resolution by the
      confocal technique dependent on the focus. Offline, the blood flow variables of
      areas of 100 microns x 100 microns were calculated. CONCLUSION: SLDF enables the
      visualisation of perfused capillaries and vessels of the retina and the optic
      nerve head in high resolution by two dimensional mapping of perfusion variables
      which are encoded by the Doppler signal. This method achieves simultaneously
      qualitative and quantitative evaluation of capillary blood flow of distinct areas
      of the capillary meshwork.

PMID- 8562551
TI  - Effects of posterior capsular disruption on the outcome of phacoemulsification
      surgery.

PMID- 8562552
TI  - Ulcerative keratitis in a person wearing daily disposable contact lenses.

PMID- 8562553
TI  - Pigmented conjunctival epithelial dysplasia in an HIV positive African: detection
      of human papillomavirus type 16.

PMID- 8562554
TI  - Presumed ocular larva migrans presenting with features of diffuse unilateral
      subacute neuroretinitis.

PMID- 8562555
TI  - Candida endophthalmitis.

PMID- 8562556
TI  - Congenital stationary nightblindness in a patient with osteopetrosis.

PMID- 8562557
TI  - An unusual impediment to spectacle wear: pilomatrixoma.

PMID- 8562558
TI  - Ectopic teeth in the orbit of a neonate.

PMID- 8562559
TI  - Orbital coccidioidomyosis presenting as a lacrimal gland fossa mass.

PMID- 8562560
TI  - A case of primary orbital melanoma treated by local excision.

PMID- 8562561
TI  - Bilateral sudden visual loss in Albright's syndrome.

PMID- 8562562
TI  - Magnetic resonance imaging and the dangers of orbital foreign bodies.

PMID- 8562563
TI  - The effects of diffusion and viscosity on ruminant faecal excretion of markers in
      a simple compartmental model.
AB  - Using equations obtained in a previous analysis, results are computed numerically
      which illustrate the effects of diffusion and viscosity on faecal excretion
      patterns of markers in ruminants. Results are first given for plug flow, a
      velocity gradient produced by viscosity, and diffusion, each mechanism operating
      alone. Plug flow gives a period during which no marker appears in the faeces,
      then a sharp increase in faeces marker concentration, followed by rapid washout.
      A velocity gradient gives a more gradual appearance of marker in the faeces
      followed by a slower washout. Diffusion alone (although not realistic for
      ruminant marker kinetics) can give early appearance of marker followed by slow
      washout. Combining diffusion with a velocity gradient produced by viscosity can
      give a range of behaviour, depending on the effective diffusion coefficient, D';
      an approximate method is used to compute these solutions. Because plug flow with
      no velocity gradient plus diffusion gives results similar to convective flow with
      a velocity gradient plus diffusion, we believe it will not be possible to
      determine the main mechanisms defining marker outflow patterns from observations
      of marker kinetics alone, and more detailed investigations will be needed.
      Although estimates of quantities such as mean transit time are unaffected by
      detailed mechanism, the interpretations of measures such as sigmoidicity,
      sharpness of the faecal marker concentration v. time curve, and length and nature
      of the washout tail are highly dependent on mechanism.

PMID- 8562564
TI  - Relationship between diet composition and body mass index in a group of Spanish
      adolescents.
AB  - The dietary patterns of sixty-four adolescents (thirty-seven young men and twenty
      seven young women) between 15 and 17 years of age were examined by analysis of
      food, energy and nutrient intakes, over a period of 5 d, including a Sunday.
      Adolescents were identified for inclusion in two study groups: (1) overweight and
      obese subjects (O) with a BMI (kg/m2) > or = 75th percentile, and (2) subjects of
      normal weight (NW) with BMI < 75th percentile. The study was designed to
      investigate the differences between the energy and nutrient intakes of NW and O
      adolescents. No differences were found in energy intake between NW and O
      adolescents. However, O subjects derived a greater proportion of their energy
      from proteins (19.8% v 16.4% for NW subjects) and fats (45.4% v. 38.7% for NW
      subjects), and less from carbohydrates (34.6% v. 44.6% for NW subjects). Also, O
      subjects consumed significantly larger amounts of cholesterol. In order to
      prevent obesity and avoid the disorders associated with this condition, it
      appears necessary not only to regulate energy intake, but also to control the
      composition of the diet. Given that it is during infancy that feeding habits are
      developed, it is important to ensure that correct habits are acquired. Special
      attention should be given to improving the dietary habits of overweight and obese
      children and adolescents.

PMID- 8562565
TI  - Validation of dietary history method in a group of elderly women using
      measurements of total energy expenditure.
AB  - The objective of the present study was to validate energy intake data, obtained
      by dietary history, in twelve elderly women aged 69-82 years. Energy and protein
      intakes were obtained using the dietary history method with a reference period of
      30 d. Reported energy intake was compared with total energy expenditure (TEE)
      measured on two consecutive days in a respiration chamber. Reported protein
      intake was compared with mean N excretion from four 24 h urine collections. Mean
      reported energy intake was 7.2 (SD 1.5) MJ/d which was lower than TEE (P =
      0.059). Reported protein intake was 64 (SD 13) g/d and lower than estimated
      protein intake (P = 0.053). The percentage underestimation was not related to
      body weight or percentage body fat. Subjects with a relatively high TEE or a
      relatively high estimated protein intake underestimated their energy intake to a
      greater extent. The discrepancy between reported energy intake and TEE was
      positively associated with the discrepancy between reported and estimated protein
      intakes. The results of this present study show an underestimation of energy
      intake of about 12% when using the dietary history method. Physical activity
      diaries completed in the chamber and during 4 d at home, as well as pedometer
      counts, indicated a higher level of physical activity in the free-living
      situation compared with the chamber situation. This suggests that the actual
      underestimation of energy intake may be even higher in this group of elderly
      women. These results have implications for the use of the dietary history method
      in, for example, epidemiological studies carried out in elderly subjects.

PMID- 8562566
TI  - High doses of dietary arginine during repletion impair weight gain and increase
      infectious mortality in protein-malnourished mice.
AB  - There is considerable evidence for the beneficial effects of dietary arginine, a
      conditionally-essential amino acid that enhances anabolism and T-cell function.
      However, the safety and efficacy of higher doses of arginine supplementation
      following infection have not been investigated completely. These issues were
      explored therefore, in a murine model of malnutrition and infection. Severe
      protein malnutrition was induced by feeding mice for 6 weeks on an isoenergetic
      diet containing only 10 g protein/kg. Mice were then allowed to consume diets
      with normal amounts of protein (200 g/kg) with 50 g/kg provided as amino acid
      mixtures of glycine and arginine in which the arginine content ranged from 0 to
      50 g/kg. During the repletion period a significant weight gain was noted in the
      groups fed on diets with either 10 or 20 g arginine/kg, but not in the group fed
      on the diet with 50 g arginine/kg, compared with the diet with 0 g arginine/kg.
      Mortality rates after infection with Salmonella typhimurium were not decreased by
      the addition of 10 or 20 g arginine/kg to the diet, and were in fact worsened by
      supplementation with 50 g arginine/kg. The results of the present study showed
      that not only are the beneficial effects of arginine supplementation after
      infection lost when high doses are administered, but also that these high doses
      become toxic. Mice fed on higher doses showed significant impairment of weight
      gain and an increase in mortality rates.

PMID- 8562567
TI  - The substrate-specific impairment of oxidative phosphorylation in liver
      mitochondria from high-protein-fed chickens.
AB  - Chickens fed on semi-purified low (7%) or high (61%) protein-energy diets for 14
      or 17 d were used for determinations of oxidative phosphorylation and specific
      amounts of mitochondrial protein in liver. The ADP:oxygen (ADP:O) values obtained
      when pyruvate+malate were used as substrates were significantly reduced in the
      high-protein-fed group after the 4th day compared with those for the group fed
      the low-protein diet, while the differences in ADP:O values between the two
      treatments when L-glutamate was used as substrate were found to be significant on
      the 14th day. At any feeding period no significant differences in ADP:O values
      were observed between the two groups when alpha-ketoglutarate, malate, or
      octanoate+malate were used as substrates, nor in specific amounts of
      mitochondrial protein in liver. The dependency of the pyruvate+malate-supported
      respiration rate on the temperature in the reaction medium was also determined.
      The results of an Arrhenius plot showed that transition temperatures, and the
      lower and upper energies of activation, were similar for the groups fed on low-
      and-high-protein diets. Furthermore, no morphological changes in mitochondria
      were observed among chickens fed on diets with various protein levels for 14 d.
      From these results we concluded that the reduction of ADP:O value with
      pyruvate+malate of L-glutamate substrates in chickens fed on a high-protein diet
      was substrate-specific, and was not due to functional damage to the respiratory
      chain for electron flow from NAD-linked substrates to the ubiquinone pool, nor to
      modulation of properties of the inner mitochondrial membrane.

PMID- 8562568
TI  - Influence of dietary retrograded starch on the metabolism of neutral steroids and
      bile acids in rats.
AB  - Diets enriched in retrograded amylose (RS3) have been shown to lower serum
      cholesterol concentrations in rats. The possibility was tested that this
      hypocholesterolaemic effect of RS3 is caused by an increase in excretion of
      neutral steroids and/or bile acids. Six groups of ten rats were fed on purified
      diets containing either 12 or 140 g RS3/kg solid ingredients with and without
      added cholesterol (5g/kg). Low-RS3 diets, with and without added cholesterol, to
      which the bile-acid-binding resin cholestyramine (20 g/kg) was added, were used
      as reference. The high-RS3 diets v. the low-RS3 diets tended to reduce the
      increase in the total serum cholesterol concentration during the course of the
      experiment (P = 0.067), decreased serum triacylglycerol concentrations, raised
      total neutral steroids and total bile acids in caecal contents and faecal
      excretion of total bile acids, but lowered faecal excretion of neutral steroids.
      In addition, the serum concentration of total 3 alpha-bile acids was markedly
      raised by the high-RS3 diets. The high-RS3 diets raised the faecal excretion of
      lithocholic and muricholic acids, but lowered that of hyodeoxycholic acid, and
      increased the caecal amounts of lithocholic, ursodeoxycholic, beta-muricholic and
      omega-muricholic acids. Apart from the stimulation of faecal bile acids
      excretion, the effects of cholestyramine on bile acid metabolism differed at
      various points from those of RS3. Cholesterol feeding had predictable effects on
      cholesterol metabolism and led to greater elevating effects of RS3 on the faecal
      and caecal amounts of muricholic acids. The results suggest that the serum
      cholesterol-lowering effect of high-RS3 diets may be explained by an increased
      influx of neutral steroids and bile acids into the caecum, and increased faecal
      excretion of bile acids, and/or by an altered intestinal bile acid profile.

PMID- 8562569
TI  - Effect of carbohydrate source on lipid metabolism in lactating mice and on pup
      development.
AB  - The effect of long-term sucrose intake on lipid metabolism and milk composition
      was examined in lactating mice and correlated with the development of their pups.
      Female mice were weaned onto semi-purified diets containing 685 g starch or
      sucrose/kg diet. Food intake was similar on the two diets. At mid-lactation, milk
      was collected and analysed. Milk from sucrose-fed dams had a lower percentage of
      linoleic acid (18:2n-6) and a higher percentage of oleic acid (18:1n-9), although
      milk fat content was similar. Hepatic fatty acid synthesis (as measured by 3H2O
      incorporation into fatty acid) was three times faster in sucrose-fed than in
      starch-fed dams. Dietary carbohydrate had no effect on fatty acid synthesis or
      functional lipoprotein lipase (EC 3.1.1.34) activity in mammary gland, nor on
      plasma triacylglycerol concentration. Pups from first litters were killed at 11
      12 d and body composition analysed. Pups born to sucrose-fed dams were
      significantly heavier with increased body fat and higher levels of plasma glucose
      and triacylglycerol. Litters of sucrose- and starch-fed dams were cross-fostered
      at birth and killed at 10-12 d. Analysis of variance indicated that maternal
      sucrose intake, both during pregnancy and lactation, increased body fat of
      offspring. The increases in body weight and plasma triacylglycerol of preweaning
      offspring were caused primarily by maternal sucrose intake during lactation.

PMID- 8562571
TI  - Effect of magnesium deficiency on triacylglycerol-rich lipoprotein and tissue
      susceptibility to peroxidation in relation to vitamin E content.
AB  - Given the current interest in the cardiovascular complications of Mg deficiency,
      the aim of the present experiment was to investigate the effect of Mg deficiency
      on the time-course of lipoprotein oxidation and to assess whether short-term Mg
      deficiency results in vitamin E depletion that predisposes lipoproteins and
      tissues to subsequent oxidation. Weanling rats were pair-fed for 8 d with control
      and Mg-deficient diets respectively. Plasma triacylglycerol and alpha-tocopherol
      levels were significantly greater in Mg-deficient rats compared with control
      animals. The increase in plasma apolipoprotein B concentration indicated that a
      corresponding increase in plasma triacylglycerol-rich lipoproteins (TGRLP)
      occurred in Mg-deficient animals. Hyperlipaemia was associated with modifications
      in the composition of TGRLP. The proportion of triacylglycerols was elevated
      whereas that of cholesterol and protein was reduced, and Mg deficiency resulted
      in a slight significant reduction in alpha-tocopherol content. When the TGRLP
      fractions were subjected to in vitro Cu-induced oxidation the lipoprotein
      fractions from Mg-deficient rats were more susceptible to oxidative damage than
      lipoprotein fractions from control rats. Mg deficiency did not modify the alpha
      tocopherol content of liver, heart and skeletal muscle. However, after exposure
      of tissue homogenates to Fe-induced lipid peroxidation, thiobarbituric acid
      reactive substances were significantly higher in tissues from Mg-deficient rats
      compared with those from control rats. These results complement previous
      findings, showing that Mg deficiency increases the susceptibility of TGRLP and
      tissues to peroxidation and suggest that oxidative damage is not the result of a
      decrease in vitamin E antioxidant status.

PMID- 8562570
TI  - The influence of the period of adaptation on the digestibility of diets
      containing different types of indigestible polysaccharides in rats.
AB  - In balanced experiments with rats the influence of the period of adaptation on
      nutrient digestibility in diets containing cellulose (CEL), guar gum (GG), pectin
      (PEC) or retrograded high amylose maize starch (RS) was studied. Inclusion level
      was 80 g/kg diet DM except for the retrograded high-amylose maize starch, where
      the level was 316 g/kg diet DM. A diet containing normal maize starch only acted
      as a control diet (FF). The apparent digestibilities of DM, NSP, starch and
      protein were determined after adaptation periods of 4 d and 2, 4, 6 and 8 weeks.
      The digestibility of nutrients was affected by diet (P < 0.001) as well as by the
      period of adaptation (P < 0.001). The digestibilities of DM, NSP and starch
      increased asymptotically during the course of the experiment. The asymptotic
      progress over time was most pronounced for the GG, PEC and RS diets. The
      estimated periods of adaptation required for stable DM digestibility were
      approximately 1 week for the GG, PEC and RS diets and < 4 d for the FF and CEL
      diets. The digestibility of NSP in the GG and PEC diets was also stable after
      approximately 1 week, while it was stable from < 4 d for the CEL diet. However,
      PEC increased the faecal content of uronic acids for at least 2 weeks. A stable
      starch digestibility required 1 month in the case of RS and 3-10 d for the other
      diets. The high faecal content of glucose for the RS diet decreased during all 8
      weeks but was still high at the close of the experiment. The apparent protein
      digestibility changed over time in a parabolic rather than an asymptotic fashion.
      The GG, PEC and RS diets increased the amount of N excreted by the faecal route.

PMID- 8562572
TI  - Serum clearance and urinary excretion of pteroylmonoglutamic acid in gestating
      and lactating dairy cows.
AB  - The present experiment was undertaken to verify if the demand of tissues for
      pteroylglutamic (folic) acid, evaluated by serum clearance and urinary excretion
      of folates, is different between multiparous dairy cows in late gestation (five
      gestating dry cows, 52.6 (SD 8.4) d before parturition), and in early lactation
      (four lactating non-gestating cows, 18.0 (SD 5.9) d after parturition). On day 1
      the cows received one intravenous (i.v.) injection of 50 micrograms
      pteroylmonoglutamic acid/kg body weight (BW). Blood samples were taken at 0, 5,
      15, 30 min, 1, 2, 4, 8 and 24 h after the i.v. injection. On day 3 the cows
      received one intramuscular (i.m.) injection of 0.3 mg pteroylmonoglutamic acid/kg
      BW. Blood and urine samples, as well as urine volume, were taken at 0, 1, 2, 4,
      8, 12, 24, 36 and 48 h after the i.m. injection. On days 5, 6 and 7 a daily i.m.
      injection of 0.5 mg pteroylmonoglutamic acid/kg BW was given in an attempt to
      saturate tissues with folates. Then the cows received one i.v. (day 8) and one
      i.m. (day 10) injection of pteroylmonoglutamic acid according to the same
      procedures described previously for days 1 and 3. On day 12 plasma volume was
      determined. Before tissue saturation, serum clearance of folates during the 24 h
      following an i.v. injection was similar for gestating and lactating cows but
      after tissue saturation serum clearance was slower for lactating than gestating
      cows (stage x saturation, P = 0.04). The percentage of folates excreted in urine
      was not affected by the physiological stage (P > or = 0.6) or the level of tissue
      saturation (P > or = 0.5). In conclusion, serum clearance and urinary excretion
      of pteroylmonoglutamic acid seem to support the hypothesis that, in multiparous
      cows, although there are no deficiency symptoms, tissue demand for folic acid is
      high, especially during gestation.

PMID- 8562573
TI  - Polyols, breath hydrogen and fermentation revisited.

PMID- 8562574
TI  - Vitamin A and retinoids.

PMID- 8562575
TI  - Effect of accumulation of CO2 on the survival of immature pigs in a confined
      atmosphere. A: Gas exchange.
AB  - Our purpose is to develop a survival strategy for man trapped in a confined
      space. We used immature pigs to assess the applicability of findings in rats for
      a larger mammal. The pig consumed oxygen in a sealed chamber until hypoxic
      collapse. We measured blood pressure, oxygen consumption, inspired O2 and CO2,
      minute ventilation, ECG and body temperatures, in three groups: no accumulation
      of CO2; CO2 level maintained at 5%, and maximal accumulation of CO2. Hypoxic
      oxygen consumption and ventilation were affected by the presence of CO2. Despite
      the pig's body mass being two orders of magnitude greater than that of the rat,
      its terminal PIO2 (35.9 torr) did not differ from that of the rat (35.3 torr).
      Accumulation of CO 2 had no significant effect on the terminal PIO2.

PMID- 8562576
TI  - Effect of accumulation of CO2 on the survival of immature pigs in a confined
      atmosphere. B: Blood gas exchange.
AB  - As part of a study for developing survival strategy for humans in a confined
      space, we used immature pigs to assess the applicability of findings in rats and
      to evaluate the effect of body size. The cannulated unanesthetized animal was
      placed in a sealed chamber and depleted the oxygen until hypoxic collapse. Three
      groups were: no accumulation of CO2, CO2 maintained at 5%, and maximal
      accumulation of CO2. In hypoxia arterial and venous oxygen tension were higher in
      the pigs exposed to CO2 than in the no CO2 pigs. Oxygen extraction increased and
      oxygen transport decreased in hypoxia in the presence of CO2. Similarity in the
      P50 of the oxygen dissociation curve may explain the similar terminal PIO2 in the
      pig and the rat. There was a positive correlation between terminal PIO2 and
      terminal venous pH.

PMID- 8562577
TI  - Effects of brief and prolonged ischemia on eicosanoid synthesis in dog and rat
      hearts.
AB  - We compared the effects of brief and prolonged myocardial ischemia on tissue
      prostaglandin synthesis. Regional ischemia was induced in dogs and maintained for
      5 or 30 minutes. Isolated rat hearts were subjected to global ischemia in a
      working heart preparation for periods of 5 or 20 minutes. De novo synthesis of
      prostaglandins PGE2 and PGF2 alpha was measured in endocardial and epicardial
      explants from hearts subjected to transient ischemia. After 5 minutes of coronary
      ligation, PGE2 production by the ischemic canine endocardium increased by 68%,
      compared with non-ischemic tissue, and PGF2 alpha levels rose by 29%. In isolated
      rat hearts, 5-minute ischemia increased endocardial rate of PGE2 synthesis (13.2
      +/- 1.7 pmol/g/h, as compared with 6.7 +/- 0.5 under normoxic conditions).
      Ischemic stimulation of eicosanoid production by the endocardium was no longer
      apparent after 30-minute regional or 20-minute global ischemia. In contrast, the
      epicardium showed significant changes only after 30-minute ischemia and only with
      respect to PGF2 alpha (12.0 +/- 6.2 in the ischemic vs 7.1 +/- 3.2 pmol/g/h in
      the non-ischemic tissue). Ischemia-induced differences in prostaglandin
      production were attenuated in the presence of arachidonic acid or aspirin.

PMID- 8562578
TI  - Skin blood flow measurements on the breast areola.
AB  - Blood flow and thermally insulated skin temperature were measured in the aerolae
      of normal breasts by means of the non-invasive transient thermal clearance
      method. Both parameters showed high variability among different women, but also
      showed typical dependence on the subject's age: the two parameters were constant
      up to age 50, and then showed a decrease at higher ages. The decrease can be
      attributed to the normal decrease of tissue blood flow at higher age and to
      atrophy of the breast glandular tissue after menopause. Statistically significant
      higher values of blood flow and insulated skin temperature were found for the
      left breast relative to the right breast.

PMID- 8562579
TI  - Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF
      and serum of schizophrenic patients.
AB  - Some evidence points towards a possible autoimmune role in the aetiology of
      schizophrenia. Experimental findings provide contradictory results regarding
      abnormalities in cytokine production in this disorder. In the present study we
      tested the production of cytokines in CSF and serum in 16 schizophrenic patients
      and 10 healthy controls (tumor necrosis factor alpha - TNF alpha; interleukins IL
      1 beta, IL-2, IL-6, soluble IL-2 receptor). Cytokine levels were evaluated by
      radioactively-labeled antibodies (IL-1 beta, IL-2, IL-6), by enzyme-linked
      immunoassay (TNF) and by a sandwich enzyme immunoassay (soluble IL-2 receptor).
      No significant differences were found in either CSF fluid or serum levels of TNF
      and IL-2 or IL-6. Interleukin-1 beta was significantly decreased in patients' CSF
      and serum as compared to controls. Soluble interleukin-2 receptor levels were
      decreased in CSF of patients, but highly increased in their serum in comparison
      with controls. Changes in various cytokine levels in CSF fluid and serum of
      schizophrenic patients probably reflect interrelated process of growth,
      degeneration or neuroimmunological abnormalities, which may all play a role in
      the pathophysiology of schizophrenia. The present study supports evidence for
      change in immune activation, probably of peripheral origin, in schizophrenic
      patients.

PMID- 8562580
TI  - Increased amniotic fluid divalent cation concentration in preeclampsia.
AB  - Hypocalciuria due to reversibly enhanced tubular calcium reabsorption in
      preeclampsia has been previously described. As the fetus is exposed in utero to
      the toxemic environment, its kidney function may be similarly affected. We
      therefore evaluated the amniotic fluid (AF) concentrations of Ca2+, Mg2+, Zn2+,
      and Na+ in relation to creatinine in 12 preeclamptic women, 9 pregnant women with
      chronic hypertension, and 12 control pregnant women. Our data reveal an increased
      AF Ca2+, Mg2+, and Zn2+ to creatinine ratio in preeclampsia 451 +/- 283; 164 +/-
      94; 787 +/- 124 Eq/mol, respectively) as compared with chronic hypertension (256
      +/- 141; 94 +/- 46; 504 +/- 124 Eq/mol, respectively), and normal controls (274
      +/- 132; 83 +/- 19; 477 +/- 124 Eq/mol, respectively; p < 0.05). Na+
      concentration did not vary significantly among the three groups. It is suggested
      that the higher AF divalent cation concentration in preeclampsia may be due to
      lower maternal urinary excretion thereby increasing the fetal divalent cation
      load.

PMID- 8562581
TI  - A pleiotropic effect of fluoride on signal transduction in macrophages: is it
      mediated by GPT-binding proteins?
AB  - The activation of GTP-binding proteins (G-proteins) by sodium fluoride + aluminum
      (AlF4-) was shown in several cell free systems. In the intact cell, NaF +/-
      aluminum was shown to activate various signal transduction pathways and indirect
      evidence is in line with effector mechanisms involving regulation of G-protein
      activity. We have explored the effect of NaF on several components of signal
      transduction pathways in macrophages. NaF was shown to reduce intracellular ATP
      levels and to suppress agonist-induced protein tyrosine phosphorylation and
      reactive oxygen species formation. NaF led to in situ activation of nitrogen
      activated protein kinase, phospholipase A2 and PtdIns-phospholipase C. Addition
      of AlCl(3) or deferoxamine, a chelator of aluminum, had little or no effect on
      NaF mediated enzyme activation. The results suggest that at least some of the
      pleiotropic effects of NaF in intact cells may not be mediated by G-protein
      activation but rather by depletion of ATP which is essential for protein
      phosphorylation reactions.

PMID- 8562582
TI  - Are nursing practice settings a toxic work environment?

PMID- 8562583
TI  - Flexible sigmoidoscopy training for nurses.
AB  - Colorectal cancer will account for approximately 55,300 deaths in 1995. In
      addition, 138,200 new cases of colorectal cancer will occur. The American Cancer
      Society encourages accessible, affordable sigmoidoscopy by primary care
      physicians or highly trained paramedical personnel for all persons, aged 50 years
      and older, every 3 to 5 years or as advised by their physician. As a result of
      these recommendations, there has been an increase in demand for the screening
      sigmoidoscopy. The increase in requests for this examination has overwhelmed
      existing resources, including physician time, space, and staff in the ambulatory
      care setting. The Kaiser Foundation Health Plan of Georgia, Inc., has developed
      an innovative approach to performing screening sigmoidoscopies by training two
      registered nurse endoscopists to conduct these examinations. The goal of the
      nurse endoscopy program is to provide quality colorectal cancer screening within
      an established appointment standard while promoting comfort and safety.

PMID- 8562584
TI  - Mock surveys: a proactive approach to the accreditation visit.
AB  - Preparing for an accreditation visit is a challenge for the nurse manager. In
      this article, the authors describe the methods and tools developed to assist the
      Duke University Medical Center Gastrointestinal Endoscopy Unit in preparing for
      the Joint Commission on Accreditation of Healthcare Organizations review process.

PMID- 8562585
TI  - Planning for career flexibility.
AB  - Evolving changes in the nation's healthcare system are affecting nursing roles at
      all levels. Nursing and healthcare organizations have responded to these changes
      with position papers and new directions for education of the healthcare
      professions. In this article, the author discusses the current changes in the
      healthcare system that affect the nursing profession and an approach that can be
      used by nurses who are concerned about the viability of their role in their
      present position. Nurses are urged to examine their present roles in practice and
      to adapt to the new system by remaining open to change and becoming knowledgeable
      about options for change.

PMID- 8562586
TI  - GI distress: clues in the patient's medications.
AB  - All medications have potential side effects; almost every medication has
      potential gastrointestinal (GI) side effects. It is important for GI nurses to be
      able to assess clients for medication use and be able to associate medications
      with possible GI problems.

PMID- 8562587
TI  - Interventions for irritable bowel syndrome: a nursing model.
AB  - Irritable Bowel Syndrome (IBS) is a common problem affecting a significant
      portion of the U.S. population. Nurses are involved directly in the planning and
      implementing of therapeutic interventions for this patient population. Using a
      Human Response Model, the authors of this article review intervention studies for
      IBS. This model provides a context for integration of Person (vulnerability) and
      Environment (risk) factors that may modify the patient's response to a given
      therapeutic regimen. Human responses are categorized as Physiological,
      Pathophysiological, and Behavioral/Experiential. Interdisciplinary therapeutic
      strategies include motility manipulations via pharmacological agents, dietary
      modifications, and self-care enhancement. Areas for nursing research are
      described.

PMID- 8562588
TI  - Lessons in good nursing judgment related to post endoscopy.

PMID- 8562589
TI  - Polyethylene glycol electrolyte lavage solution-induced Mallory-Weiss tear.

PMID- 8562590
TI  - The newest proton pump inhibitor.

PMID- 8562591
TI  - Sequence analysis of phosphorothioate oligonucleotides via matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry.
AB  - Modification of the natural phosphodiester backbone of deoxyribooligonucleotides
      can impart increased biostability via nuclease resistance. Further, uniform
      incorporation of phosphorothioate linkages renders oligonucleotides highly
      resistant to reagents traditionally used in sequencing reactions. As a
      consequence, analytical tests crucial for establishing the identity of such
      oligonucleotide drugs are less informative. To circumvent this problem, chemical
      oxidation has been employed for converting the phosphorothioate to the uniform
      phosphodiester, thereby facilitating enzymatic degradation. Following oxidation,
      exonucleases which sequentially cleave individual bases from the 3' or 5'
      terminus of the oligonucleotide or base-specific cleavage chemicals were used to
      facilitate sequence identification of the oligonucleotide. Matrix-assisted laser
      desorption ionization-time-of-flight/mass spectrometry (MALDI-TOF/MS), previously
      used to sequence natural phosphodiester DNA, was then used to sequence the
      chemically oxidized phosphorothioate. Sequential enzymatic cleavage of
      desulphurized phosphorothioates in combination with MALDI analysis not only
      provides a viable alternative to radiolabeling as used in conventional sequencing
      approaches (e.g. Maxam-Gilbert), but also enables rapid sequencing of
      phosphorothioate oligonucleotides, for routine drug analysis.

PMID- 8562592
TI  - Considerations in the development of a sensitive HPLC assay for human epidermal
      growth factors in human plasma.
AB  - A sensitive assay was developed for human epidermal growth factors (hEGF) 1-48
      (dosed), hEGF 1-53 (endogenous), without interference from potential metabolites
      hEGFs 1-47 or 1-46. Spiked human plasma samples were injected directly, utilizing
      on-line immunoaffinity HPLC (anti-hEGF) clean-up. No change in capacity was noted
      after 81 cycles. After release from the immunoaffinity column, the fragments were
      further resolved by strong cation-exchange (SCX) via a column switching valve.
      Method development also required interfacing immunoaffinity, ion-exchange, and
      detection components. Immunoassays on collected fractions yielded a detection
      limit of 1 microgram ml-1, although a detection limit of 75 pg ml-1 appears
      feasible.

PMID- 8562593
TI  - Determination of a glycine/NMDA receptor antagonist in human plasma and urine
      using column-switching high-performance liquid chromatography with ultraviolet,
      fluorescence and tandem mass spectrometric detection.
AB  - High-performance liquid chromatography (HPLC) assays using ultraviolet (UV) and
      fluorescence (FL) detection were developed and compared with a liquid
      chromatography/tandem mass spectrometry (LC/MS-MS) method for determination of
      the glycine receptor antagonist 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(1H)
      quinolone (L-701, 324, I) in human plasma and urine. The drug and internal
      standard (II) were isolated from the biological matrix through liquid-liquid
      extraction. In the HPLC-UV and HPLC-FL methods, the samples were initially
      injected onto a Cyano BDS Hypersil column, and the chromatographic region
      containing the peaks of interest was heart-cut onto an analytical C-18 BDS
      Hypersil column via a column-switching device. The analyte was quantified by
      monitoring either absorbance at 226 nm or fluorescence at 385 nm following 230 nm
      excitation. The limit of quantitation for I extracted from 1 ml of plasma or
      urine was 5 ng ml-1, and the assays were validated in the concentrated range of 5
      200 ng ml-1. The LC/MS-MS method also utilized a column-switching protocol and
      was validated in the concentration range of 1-200 ng ml-1. Both assays provided
      data with precision and accuracy within less than 10% for all points in the
      standard curve range.

PMID- 8562594
TI  - A 19F NMR study of lomefloxacin in human erythrocytes and its interaction with
      hemoglobin.
AB  - 19F NMR spectroscopy of a model fluoroquinolone, lomefloxacin, in an erythrocyte
      suspension showed separate resonances for the intra- and extra-cellular
      compartments. The intra-cellular peak revealed significant line broadening of the
      fluorine signals of lomefloxacin. Line broadening also occurred in the presence
      of oxyhemoglobin (HbO2), hematin, globin and iron. This evidence indicated that
      lomefloxacin interacted with these compounds; however, ultrafiltration
      experiments indicated that there was only weak binding (5%) of lomefloxacin to
      HbO2. 19F and 31P NMR spectroscopy revealed that lomefloxacin may compete with
      2,3-diphosphoglycerate for its binding site on HbO2. An apparent partition
      coefficient of 1.90 +/- 0.15 was observed for lomefloxacin in human erythrocytes,
      utilizing LC analysis.

PMID- 8562595
TI  - Automated analytical systems for drug development studies. 3. Multivessel
      dissolution testing system based on microdialysis sampling.
AB  - An automated system consisting of a six-vessel dissolution apparatus,
      microdialysis sampling, STT E6 multiposition switching valve and a liquid
      chromatograph was assembled to measure dissolution profiles of immediate and
      sustained-release tablets. A DL-5 microdialysis loop probe (BAS, Inc.) was
      immersed in each dissolution vessel and perfused with a suitable medium for
      sampling. The dialystate from each vessel was injected sequentially onto an on
      line liquid chromatography (LC) system for automated analysis. The STT E6
      multiposition switching valve was used to sample up to six vessels
      simultaneously. After addressing issues related to sample carry-over and between
      probe variability, the automated system was used in a reproducible manner (RSD <
      3%) to measure the dissolution of immediate-release acetaminophen tablets and
      Accutrim (containing 75 mg phenylpropanolamine HCl) 16 h Precision Release
      tablets. An uneven injection time sequence was used to monitor three
      acetaminophen tablets per dissolution run using the automated system and each
      vessel was sampled about every 6.5 min. However, with Accutrim 16 h Precision
      Release tablets, a longer sampling interval (10 min) was used, the six tablets
      could be tested in each dissolution run. The dissolution profiles of
      acetaminophen and Accutrim tablets measured using the automated multivessel
      dissolution system compared well with manual and automated single-vessel
      dissolution systems.

PMID- 8562596
TI  - Stereospecific high-performance liquid chromatographic assay of lomefloxacin in
      human plasma.
AB  - This report describes an HPLC assay developed for the quantification of the
      enantiomers of lomefloxacin (LFLX), a quinolone antibiotic, in plasma. Following
      addition of racemic acebutolol (internal standard, IS), plasma samples were
      extracted at pH 7 with a mixture of chloroform-isopentyl alcohol-diethyl ether
      (71.25:3.75:25, v/v/v). The organic layer was evaporated, and LFLX and IS
      enantiomers in the resulting residue were derivatized with chloroform solutions
      of 1% triethylamine and 1% (S)-(+)-(1-naphthyl)ethyl isocyanate, followed by 2%
      ethyl chloroformate (ECF) 1 min later. Ethanolamine was added 30 s after the
      addition of ECF. The enantiomers were separated as diastereomers on an 8 x 100 mm
      Radial Pak normal phase column using a mobile phase of hexane-chloroform-methanol
      (64.5:33:2.5, v/v/v) pumped at 2.0 ml min-1. The IS was detected by fluorescence
      at 245 and 420 nm (excitation and emission, respectively) during the first 12
      min, after which time the wavelengths were 280 and 470 nm for detection of LFLX.
      The method: (1) was sensitive and showed excellent linearity (10-1000 ng ml-1, r2
      > 0.99) between added enantiomer concentrations and peak-area-ratio (LFLX/IS);
      and (2) separated LFLX and IS enantiomers within 25 min. The assay is suitable
      for the quantification of LFLX enantiomers in plasma samples.

PMID- 8562597
TI  - Degradation of lyophilized and reconstituted MACROSCINT (DTPA-IgG): precipitation
      vs. glucosylation.
AB  - Diethylenetriaminepentaacetic anhydride (DTPA) conjugated to IgG (DTPA-IgG) and
      labeled with 111In is useful for detecting focal sites of infection and
      inflammation (R.H. Rubin, A.J. Fischman, R.J. Callahan, B. Khaw, F. Keech, M.
      Ahmad, R. Wilkinson and H.W. Strauss, 111In-labeled nonspecific immunoglobulin
      scanning in the detection of focal infection, N. Engl. J. Med., 321 (1989) 935
      940). MACROSCINT contains DTPA-IgG formulated as a lyophile from a citrate buffer
      containing maltose. Exposure of both reconstituted and lyophilized MACROSCINT to
      intense light resulted in degradation primarily via formation of precipitating
      aggregates. However, lyophilized and reconstituted MACROSCINT responded
      differently to thermal stress. Reconstituted MACROSCINT subjected to thermal
      stress (65 degrees C) also degraded through formation of precipitating
      aggregates. In contrast, exposure of lyophilized MACROSCINT to thermal stress (65
      degrees C) resulted primarily in an increase in the molecular size of the
      MACROSCINT DTPA-IgG monomer. This increase in molecular size was a function of
      both the moisture content in the vial and the amount of time for which the sample
      was stressed, but was not a function of the conjugation with DTPA. Monosaccharide
      analysis of the samples demonstrated that this increase in molecular size
      corresponded to an increase in the amount of glucose covalently attached to the
      IgG. These data suggest that the increase in molecular size as a function of
      thermal stress is due to the covalent attachment of maltose, which is a glucose
      disaccharide present in the lyophile as an excipient, to the IgG. This
      degradation pathway was only observed in the lyophile.

PMID- 8562598
TI  - Quantitation of proteins using HPLC-detector response rather than standard curve
      comparison.
AB  - Modern high performance liquid chromatography (HPLC)-diode array detectors with
      features such as multiple wavelength monitoring are capable of maintaining a high
      degree of response reproducibility over extended periods of time. This
      reproducibility suggests that detector response factors, rather than dilution
      based standard curves, might be used to measure concentrations of proteins and
      pharmaceuticals. Four different HPLC methods were used to analyze a single
      protein and to test the accuracy and precision of measurements using response
      factors. These results were compared to the accuracy and precision obtained using
      fitting to a standard curve. Protein solutions were analyzed by HPLC after the
      concentration was determined by quantitative amino acid analysis. The extinction
      coefficient at 277 nm of these protein solutions was determined by UV
      spectroscopy as well as calculated based on the known amino acid composition. The
      theoretical extinction coefficient calculated by summing the extinction
      coefficient of the individual amino acids was within 2% of the experimental
      value. Response factors at 215 and 277 nm were calculated using the peak area
      produced by the injection of a known amount of protein. When the experimental
      extinction coefficient was used to calculate the expected HPLC-signal response
      (peak area = absorbance x duration), the recovery of the protein (accuracy) was
      100% if measured at 215 nm and between 90 and 94% when measured at 277 nm. The
      ruggedness of the recovery was between 2.6 and 4% relative standard deviation,
      depending on the HPLC-method. It was found that the quantitation was at least as
      accurate when calculated from the peak area using the response factor as when a
      standard curve was used.

PMID- 8562599
TI  - Determination of film-coated tablet parameters by near-infrared spectroscopy.
AB  - Near-infrared (near-IR) spectroscopy was used in the determination of three
      parameters of theophylline tablets film-coated with ethylcellulose. Spectra of
      individual intact tablets were collected on two near-IR spectrometers: a grating
      based spectrometer, and an acousto-optic tunable filter spectrometer.
      Calibrations were developed for the prediction of the time to 50% dissolution
      (t50%) of theophylline for tablets of varying coat thickness, for the
      determination of the thickness of the ethylcellulose coat applied, and for the
      prediction of the hardness of coated tablets. Principal component analysis was
      performed on the spectra prior to calibration development. The standard errors of
      calibration (SEC) and prediction (SEP) for determination of dissolution rates
      were 2.8 and 6.6 min, respectively. The SEC for the coating thickness calibration
      was 0.0002 inches, with an SEP of 0.00024 inches, and the SEC and SEP for the
      determination of tablet hardness were 0.54 and 0.62 kilopons, respectively.

PMID- 8562600
TI  - A comparison of two quality assessment methods for emulsions.
AB  - A common method of assessing the quality of emulsions is to evaluate the size
      distribution of the globules of the internal phase. The primary aim of this work
      is to compare the sensitivity of this test to an alternative method. The sizes of
      the globules of two emulsions, an oral emulsion and a total parenteral nutrition
      (TPN) emulsion, were determined using a light microscope. Globule size analyses
      were performed upon preparation and during storage of the emulsions. Using a
      computer program specially developed for this study, the recorded diameters were
      placed into size groups and the volumes of each of the measured globules was
      determined. For each size group, the total volume of all the globules within the
      group and the volume percentage of the oil phase represented by the group were
      calculated. The volume distribution of the internal phase across the size groups
      was found to predict emulsion instability better than the globule number
      distribution and thus is a better determinant of emulsion quality. This technique
      may have general application in the evaluation of TPN emulsions and other
      spheres, such as liposomes.

PMID- 8562601
TI  - Ion chromatography of methanesulfonic acid in pharmaceuticals.

PMID- 8562602
TI  - Determination of inorganic ions of clinical interest: state-of-the-art and
      trends.
AB  - An overview is presented of techniques, analysers and methods currently available
      for the determination of inorganic ions of interest in clinical laboratories;
      methods include those based on activation and inhibition of enzymatic reactions
      by these target analytes. The foreseeable, trends in this area are also
      discussed.

PMID- 8562603
TI  - The analysis of aminoglycoside antibiotics by capillary electrophoresis.
AB  - The analyses of aminoglycoside antibiotics by capillary electrophoresis utilizing
      borate complexation and direct UV detection are discussed. Twelve aminoglycosides
      were studied and separated to demonstrate identification capabilities, with
      migration time RSDs from 0.21 to 0.44% (n = 6) for individual components. This
      buffer system permitted the detection of minor impurities such as precursors or
      closely related fermentation products. Quantification of dihydrostreptomycin and
      streptomycin was accomplished in 160 mM sodium tetraborate decahydrate with
      linearity over the range 0.050-1.0 mg ml-1. Determination of the purity of bulk
      dihydrostreptomycin was possible by the addition of the cationic surfactant
      myristyltrimethylammonium bromide. This reversed the electroosmotic flow, thereby
      reversing the migration order, and causing the streptomycin impurity to migrate
      before the dihydrostreptomycin main peak. Quantification was also demonstrated
      with the closely related compounds amikacin, bekanamycin, kanamycin A, and
      tobramycin, using sisomicin as an internal standard. The reproducibility of the
      method was typically 2-3% over 1 day, and 2% day-to-day. These studies illustrate
      the use of capillary electrophoresis for the identification and quantification of
      selected aminoglycosides as potential alternative methods to the assays given by
      the US Pharmacopeia.

PMID- 8562604
TI  - Influence of methodological aspects on tissue drug concentration estimation.
AB  - Fundamental studies in tissue drug extraction have been made using rokitamycin as
      a test probe. Radiolabelled rokitamycin was administered intravenously to 12
      rats. Lungs and femurs were excised a few minutes later. Rokitamycin was
      extracted from lungs using six procedures (based either on ion-pairing,
      dissolution or deproteinization) whose performances (mean recovery and
      reproducibility) were compared. Three grinding procedures were also compared for
      the extraction of rokitamycin from bone: pulverization by a magnetic stirring bar
      in a liquid nitrogen bath, slicing into small pieces and crushing with pestle and
      mortar. The effect of binding proteins (albumin or alpha 1-acid glycoprotein) in
      the extraction mixture was also evaluated. Magnetic stirring bar grinding was the
      most efficient. Deproteinization was necessary to obtain the highest recovery,
      but the agent had to be chosen carefully. Binding proteins either had no effect
      or decreased the recovery of rokitamycin. Recovery from bone was lower than that
      from lung. Binding to cellular components in the post-extraction pellet was only
      3% (lung) and 9% (bone). It is concluded that a careful optimization of the
      extraction procedure of a drug from a tissue allows quantitative and reproducible
      measurement of its concentration.

PMID- 8562605
TI  - The effect of lipophilicity on the protein binding and blood cell uptake of some
      acidic drugs.
AB  - Quantitative relationships between lipophilicity (characterized by the octanol
      water partition coefficient) and binding to both human plasma proteins and blood
      cells have been studied in a group of model anionic drugs (benzoic and
      phenylacetic acid derivatives). Protein binding in plasma and accumulation in
      blood cells in suspension increases with increasing lipophilicity. For
      quantitative evaluation, the equation log R = a + b log D has been employed,
      where R is the bound-to-free drug ratio, D is lipophilicity, and a and b are
      constants. Whereas the protein bound-to-free drug ratio is proportional to drug
      lipophilicity, the cell bound-to-free drug ratio correlates with lipophilicity to
      the power 0.685. Distribution in whole blood is affected by protein binding and
      also by cell accumulation. In blood, the free drug fraction and the fraction in
      blood cells decrease with increasing lipophilicity, whereas the protein-bound
      fraction correspondingly increases.

PMID- 8562606
TI  - Radioimmunoassay of drugs of abuse in hair. Part 2: The determination of
      methadone in the hair of known drug users.
AB  - This communication addresses the analytical problems associated with the analysis
      of hair specimens from known users and misusers of the synthetic opioid
      methadone. An adapted radioimmunoassay and a previously developed preanalytical
      decontamination procedure have been applied to samples from known drug users. The
      removal of drugs from the hair surface by washing and the effect of proprietary
      hair treatments on methadone entrapped in the hair have also been investigated.
      Pre-analytical washing reduced methadone levels by up to 29%, whilst hair
      colouration and peroxide bleaching were found to reduce levels by up to 21% and
      50% respectively. Methadone assay of extracts from dated hair segments were shown
      to provide long-term histories of methadone intake, under controlled and non
      controlled conditions. Evidence that a dose relationship between hair drug levels
      and intake may exist is presented. Results of hair analysis, expressed as ng
      methadone/mg hair, from drug users (range 0.20-10.63) are compared to a pre
      determined cut-off of 0.1 ng methadone/mg hair, obtained from the analysis of a
      known drug free population (n = 23).

PMID- 8562607
TI  - Comparison of sandwich enzyme-linked immunoadsorbent assay and radioimmunoassay
      for determination of exogenous glucagon-like peptide-1(7-36)amide in plasma.
AB  - A sensitive sandwich enzyme-linked immunoadsorbent assay (ELISA) for
      determination of exogenous glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide)
      in plasma samples from pharmacokinetic studies is described. The assay employs an
      N-terminally directed antibody and a C-terminally directed antibody. The ELISA
      has a working range from 10 to 500 pmol l-1, and can be applied to plasma samples
      from humans, dogs, pigs, minipigs, cats, rabbits, and rats. The assay was
      compared to a validated radioimmunoassay (RIA), employing an antibody directed
      against the mid-region of GLP-1. After s.c. administration of GLP-1(7-36)amide,
      the plasma immunoreactivity of GLP-1 (P-GLP-1-IR) measured by ELISA was markedly
      lower than P-GLP-1-IR measured by RIA. After HPLC fractionation of plasma samples
      with subsequent RIA and ELISA analyses of the fractions, this difference was
      shown to be due to cross reaction with biologically inactive fragments of GLP-1(7
      36)amide in the RIA but not in the ELISA.

PMID- 8562608
TI  - Simultaneous determination of enalapril maleate and hydrochlorothiazide by first
      derivative ultraviolet spectrophotometry and high-performance liquid
      chromatography.
AB  - Two methods are described for the simultaneous determination of enalapril maleate
      and hydrochlorothiazide in combined pharmaceutical tablets. The first method
      depends on first-derivative ultraviolet spectrophotometry, with zero-crossing and
      peak-to-base measurement methods. The first-derivative amplitudes at 224 and 260
      nm were selected for the assay of enalapril maleate and hydrochlorothiazide,
      respectively. The second method is based on high-performance liquid
      chromatography on a reversed-phase column using a mobile phase of acetonitrile
      water (20:80, v/v) (pH 3.8) with programmable detection at 215 and 275 nm. Both
      methods showed good linearity, precision and reproducibility. The proposed
      methods were successfully applied to the determination of these drugs in
      laboratory-prepared mixtures and in commercial tablets.

PMID- 8562609
TI  - Biotransformation of linogliride, a hypoglycemic agent in laboratory animals and
      humans.
AB  - Following oral administration of linogliride, a hypoglycemic agent, to rat (50 mg
      kg-1), dog (30 mg kg-1), and man (100 mg per subject), plasma, urine, and fecal
      extract sample pools were obtained. Nine metabolites plus unchanged linogliride
      were isolated and identified. The number of metabolites identified were: rat (5),
      dog (9), and man (1). In each species, more than 78% of the administered dose was
      recovered in the urine pools. Identified metabolites were estimated to account
      for > 82% of the total amounts of drug-related sample in urine pools and > 50% in
      plasma and fecal extract pools. Formation of linogliride metabolites in the three
      species can be described by four proposed pathways: pyrrolidine hydroxylation,
      aromatic hydroxylation, morpholine hydroxylation, and imino-bond cleavage.
      Comparison of the proposed metabolic pathways among species reveals a similarity
      between rat and dog. In these two species, pyrrolidine hydroxylation was
      quantitatively the most important pathway, with 5-hydroxylinogliride and dominant
      hypoglycemic active metabolite in all sample pools. Further oxidation of 5
      hydroxylinogliride resulted in the formation of five minor metabolites. The other
      three pathways appeared to be quantitatively unimportant. Metabolism of
      linogliride in man occurred to a very limited extent. More than 90% of the total
      linogliride-related material in plasma was the unchanged drug. Greater than 76%
      of the administered dose was excreted unchanged in the urine. Only 5
      hydroxylinogliride was identified in minor amounts in human samples.

PMID- 8562610
TI  - Simulation of fractograms of fat emulsions in power-programmed sedimentation
      field-flow fractionation (SdFFF).
AB  - A quasi-empirical approach to the simulation of fractograms was examined to
      verify that the elution behavior of emulsions in power-based field programmed
      sedimentation field-flow fractionation (SdFFF) is consistent and predictable. The
      approach was applied to Intralipid, a commercial soybean emulsion and to an
      investigational medium chain triglyceride emulsion. The simulations predicted the
      fractograms that were obtained under various conditions of field strength, field
      decay and velocity of the suspending fluid, using distribution parameters
      obtained from one preliminary measurement of size distribution profile. Predicted
      fractograms were compared to experimental ones, under various fractionating
      powers. Good agreement was observed in most cases, in which interference of the
      secondary relaxation effects was not effective. The agreement confirmed the
      applicability of the approach to emulsions and that the simulations can be used
      instead of actual experiments for the optimization of their characterization by
      power-programmed SdFFF.

PMID- 8562611
TI  - The determination of palladium in fosinopril sodium (monopril) by ICP-MS.
AB  - A rapid, sensitive ICP-MS method was developed to determine palladium in
      fosinopril sodium. The assay could not be carried out in a purely aqueous solvent
      owing to the instability of the palladium species in this media. It was found
      that the most appropriate vehicle for solubilization of this material was a
      solution of 25% (v/v) 2-butoxyethanol and water. A minimum quantifiable limit of
      0.1 microns g-1 for Pd in the sample (corresponding to 1 ng Pd mL-1 in the
      analyte solution) was obtained.

PMID- 8562612
TI  - A chemiluminescence enzyme immunoassay (CLEIA) for the determination of
      medroxyprogesterone acetate in human serum.
AB  - An enzyme immunoassay with chemiluminescence detection (CLEIA) for measuring
      serum levels of medroxyprogesterone acetate (MPA), a synthetic progestational
      agent currently used in fertility control and hormonal cancer, is reported. The
      polyclonal antiserum was obtained by immunizing rabbits with the synthetized 17
      hemisuccinate derivative of medroxyprogesterone (MPS) coupled to serum albumin.
      This antiserum does not display any cross reactivity with extracted metabolites
      or with corticosteroid analogs with modifications at positions 11 and 16. The
      same MPS coupled to alkaline phosphatase is used as tracer. For the
      chemiluminescent detection system, adamantyl-1,2-dioxetane phosphate is selected
      as substrate. The typical standard curve ranges from 18.5 to 1182 pg per well and
      displays a slope factor of 0.74, with an ED50 of 143.8 pg of MPA per well and a
      minimum detectable and maximal level of 0.83 and 12,400 pg per well respectively.
      The assay has been validated on spiked serum samples in terms of precision (intra
      and interassay coefficient variations of less than 8% and 13%, respectively),
      and of accuracy (mean recovery 105%). The validation on clinical samples
      demonstrates a good correlation of MPA serum values obtained both by
      radioimmunoassay and CLEIA. This specific and sensitive CLEIA, which requires
      less than 100 microliters of serum sample, appears to be an interesting
      alternative for the monitoring of serum levels of MPA in humans.

PMID- 8562613
TI  - Use of micellar electrokinetic capillary chromatography in the study of in vitro
      metabolism of phenol by human liver microsomes.
AB  - Micellar electrokinetic capillary chromatography (MECC) is used for analysis of
      microsome incubation samples. Phenol, a neutral analyte, is separated from
      interferences. The separation is achieved without sample clean-up. MECC is shown
      to be advantageous for situations where rapid sampling with minimum handling is
      desired.

PMID- 8562614
TI  - Determination of ibuprofen in erythrocytes and plasma by high performance liquid
      chromatography.
AB  - A high-performance liquid chromatographic (HPLC) method is described for the
      determination of ibuprofen in isolated erythrocytes and plasma. Before HPLC
      analysis ibuprofen was isolated by liquid-liquid extraction from these biological
      matrices; methylene chloride proved to be the best of the organic solvents
      tested. For the sample of erythrocytes it was necessary to carry out haemolysis
      prior to their extraction. HPLC was performed on a C-18 column with a mobile
      phase of methanol-water (220:100, v/v) acidified with perchloric acid to pH 3.
      Ultraviolet detection was at 222 nm. This method has been applied to the
      quantification of ibuprofen in rabbit erythrocytes and plasma for a
      pharmacokinetics study.

PMID- 8562615
TI  - Assay and purity control of minocycline by thin-layer chromatography using UV and
      fluorescence densitometry--a comparison with liquid chromatography.
AB  - A thin-layer chromatography (TLC) method using UV and fluoresecence densitometry
      is described for the assay and purity control of minocycline (MC). With a mobile
      phase dichloromethane-methanol-water (57:35:8, v/v/v) and a silica gel thin
      layer, previously sprayed with 10% m/v sodium edetate adjusted to pH 9.0, 4
      epiminocycline and 7-didemethylminocycline were well separated from MC and from
      each other, 7-monodemethylminocycline and 6-deoxy-6-demethyltetracycline (6
      DODMTC) were not separated from each other and were only partially separated from
      minocycline. 6-DODMTC was selectively determined by fluorescence densitometry,
      while quantification of other impurities and the assay of MC were performed by UV
      densitometry. Results obtained with qualitative TLC were compared with those
      obtained by a liquid chromatography (LC) method using a poly(styrene
      divinylbenzene) copolymer stationary phase. The correlation coefficient for TLC
      and LC results was > 0.999. For TLC the relative standard deviation for the assay
      of MC at 1.25 mg ml-1 was < 3.0% (n = 4), while for LC it was < 1.0% (n = 4).

PMID- 8562616
TI  - A liquid chromatographic assay for the stereospecific quantitative analysis of
      halofantrine in human plasma.
AB  - A stereospecific liquid chromatographic (LC) assay was developed for the
      quantification of the antimalarial drug, halofantrine, in human plasma. Following
      protein precipitation with acetonitrile, the enantiomers of halofantrine were
      extracted from human plasma using ammonium hydroxide and tert-butyl methyl ether
      hexane. A precolumn derivatization step was employed using (+)-di-O-acetyl-L
      tartaric acid anhydride to form diastereomeric derivatives of the halofantrine
      enantiomers. Chromatographic resolution of the diastereomers was performed using
      reversed-phase LC with UV detection at 254 nm. The recovery of (+/-)-halofantrine
      from human plasma at 25 and 2000 ng ml-1 was 68.2 and 61.4%, respectively. The
      derivatization yield following extraction and derivatization of 2000 ng ml-1 of
      (+/-)-halofantrine was 95.6%. Using 0.5 ml of plasma, the limit of quantification
      for each halofantrine enantiomer was 12.5 ng ml-1. Linear responses in
      analyte/internal standard peak height ratios were observed for analyte
      concentrations ranging from 12.5 to 1000 ng ml-1. Chromatograms of drug-free
      plasma showed no interfering peaks with retention times similar to those for (+)-
      and (-)-halofantrine or internal standard. Based on the validation data, the
      assay performed well over the enantiomer concentration range of 12.5-500 ng ml-1.

PMID- 8562617
TI  - Simultaneous determination of dextrorphan and guaifenesin in human plasma by
      liquid chromatography with fluorescence detection.
AB  - A sensitive liquid chromatographic (LC) method was developed and validated for
      the simultaneous determination of dextrorphan and guaifenesin in human plasma
      using fluorescence detection. Dextrorphan and guaifenesin were extracted from
      plasma by a liquid-liquid extraction procedure using chloroform containing
      laudanosine as the internal standard. A cyano column (15 cm x 46 mm i.d.,
      Spherisorb 5-CN) and a mobile phase containing acetonitrile-triethylamine
      distilled water (10:1:89, v/v/v) (pH 6) were used. The concentration-response
      relationship for dextrorphan was found to be linear over a concentration range of
      23-515 ng ml-1 with a lower limit of detection of 20 ng ml-1; the accuracy of the
      method would fall (95% confidence limit) within 9.53% and 11.07% of the true
      value for the inter-and intra-day, respectively; the inter- and intra-day
      precision, as measured by RSD, ranged from 1.88% to 30.07% (mean 2.28%) and from
      4.69% to 7.51% (mean 5.67%) over the dynamic concentration range of the method
      (33-326 ng ml-1). The concentration-response relationship for guaifenesin was
      found to be linear over a concentration range of 181-8136 ng ml-1 with a lower
      detection limit of 30 ng ml-1; the accuracy of the method would fall (95%
      confidence limit) within 9.78% and 8.04% of the true value for the inter- and
      intra-day, respectively; the inter- and intra-day precision, as measured by the
      RSD, ranged from 2.55 to 6.07% (mean 3.90%) and from 3.12 to 3.90% (mean 3.52%)
      over the dynamic concentration range of the method (435-6430 ng ml-1).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8562618
TI  - Detection and quantitation of gadolinium chelates in human serum and urine by
      high-performance liquid chromatography and post-column derivatization of
      gadolinium with Arsenazo III.
AB  - A narrow-bore high-performance liquid chromatography method was developed for
      simultaneous separation of gadolinium diethylenetriaminepentaacetic acid
      (GdDTPA), the monomethylamide (GdDTPA-MMA) and the bis-methylamide (GdDTPA-BMA)
      in human serum and urine. The Gd complexes were detected at 658 nm after post
      column derivatization with Arsenazo III. The serum samples were ultrafiltrated,
      whereas the urine samples were centrifuged and diluted before analysis. With an
      injection volume of 10 microliters on a 2.1 mm ID reversed-phase column, the
      limit of detection of GdDTPA-BMA was calculated as 0.3 microM and 1.1 microM in
      serum and urine, respectively. The method was validated with respect to GdDTPA
      BMA with a limit of quantification set to 2 microM and 10 microM in serum and
      urine, respectively. The best fit of the calibration curve was obtained using non
      linear regression according to the equation Y = A+BX+CX2 in the concentration
      ranges 2-800 microM and 10-2000 microM of GdDTPA-BMA in serum and urine,
      respectively. The precision of the method was found to range from 1 to 4% RSD.
      The recoveries of GdDTPA-BMA spiked in serum and urine were higher than 95% with
      an RSD equal to or less than 4%. The serum samples were stable for at least 5
      months when stored at -70 degrees C, and the urine samples were stable for a
      least 6 months when stored at -20 degrees C.

PMID- 8562619
TI  - Spectrophotometric determination of nizatidine in pharmaceutical formulations.

PMID- 8562620
TI  - Particulate air pollution and mortality: the Philadelphia story.

PMID- 8562621
TI  - What can we infer from findings in subgroups?

PMID- 8562622
TI  - Air pollution and daily mortality in Philadelphia.
AB  - Many recent analyses have reported associations between air pollution and
      mortality in U.S. cities. In this paper, we present the results of regression
      analyses of daily mortality in Philadelphia during the period 1973-1988.
      Pollution variables included in the analyses were total suspended particulates
      (TSP), sulfur dioxide, and ozone. We controlled for the effects of weather on
      mortality by analyzing mortality separately for each season and explicityly
      including quintiles of temperature in the regression models. In regression models
      that consider weather and pollution variables simultaneously, daily mortality is
      associated with hot days in summer [relative risk (RR) for highest quintile of
      temperature = 1.07; 95% confidence interval (CI) = 1.04-1.10], and with cold days
      in spring (RR for lowest quintile of temperature = 1.07; 95% CI = 1.04-1.10),
      fall (RR for lowest quintile of temperature = 1.05; 95% CI = 1.02-1.08), and
      winter (RR for lowest quintile of temperature = 1.04; 95% CI = 1.01-1.07). When
      all three pollution covariates and weather are considered simultaneously in the
      regression model, ozone is associated with mortality in summer (RR = 1.15; 95% CI
      = 1.07-1.24) and sulfur dioxide is associated with mortality in spring (RR =
      1.19; 95% CI = 1.06-1.33), fall (RR = 1.14; 95% CI = 1.00-1.29), and winter (RR =
      1.21; 95% CI = 1.09-1.35), where the relative risks are for incremental changes
      of 100 parts per billion in ozone and sulfur dioxide on the previous
      day.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562623
TI  - Electric blanket use during pregnancy in relation to the risk of congenital
      urinary tract anomalies among women with a history of subfertility.
AB  - To study the potential effect of prenatal exposure to electromagnetic fields on
      the occurrence of cogenital urinary tract anomalies (CUTAs) in offspring, we
      conducted a case-control study in western Washington State. CUTA cases without
      known chromosomal abnormalities were identified from the Washington Birth Defects
      Registry. Controls without birth defects were randomly selected from among
      infants born in five large hospitals in King County, WA. Mothers of cases and
      controls were interviewed to obtain information on prenatal use of electric
      blankets, electrically heated water beds, and video display terminals. After
      adjustment for potential confounders, the risk of CUTAs was found not to be
      materially associated with these prenatal exposures among all subjects. Among
      women with a history of subfertility, however, prenatal use of electric blankets
      was associated with a more than four-fold increase in the risk of CUTAs [adjusted
      odds ratio (OR) = 4.4; 95% confidence interval (CI) = 0.9-22.7]. The risk was
      greater if the exposure occurred during the first trimester (adjusted OR = 10.0;
      95% CI = 1.2-85.5). The risk also appeared to increase with increasing duration
      of electric blanket use. Despite small numbers and the potential for recall bias,
      our study indicates that identifying a susceptible population may be required for
      detecting adverse reproductive effects of electromagnetic fields.

PMID- 8562624
TI  - Poverty and death in the United States--1973 and 1991.
AB  - We conducted a survival analysis to determine the effect of poverty on mortality
      in a national sample of blacks and whites 25-74 years of age (in the First
      National Health and Nutrition Examination Survey and National Health Examination
      Follow-up Survey). We estimated the proportion of mortality associated with
      poverty from 1973 through 1984 and in 1991 by calculating the population
      attributable risk. We assessed confounding by major known risk factors, such as
      smoking, serum total cholesterol, and inactivity. In 1973, 16.1% of U.S.
      mortality among black and white persons 25-74 years of age was attributable to
      poverty; in 1991, the proportion increased to 17.7%. In 1991, the population
      attributable risk of poverty on mortality was lowest for white women, 1.7 times
      higher for white men, 2.6 times higher for black women, and 3.6 times higher for
      black men. Potential confounders explained 40% of the effect of poverty on
      mortality among women. The proportion of mortality attributable to poverty among
      U.S. black and white adults has increased in recent decades and is comparable to
      that attributable to cigarette smoking. The effect of poverty on mortality must
      be explained by conditions other than commonly recognized risk factors.

PMID- 8562625
TI  - Pancreatic cancer and occupational exposures.
AB  - We conducted a nationwide case-control study in Finland to identify occupational
      risk factors for pancreatic cancer. We constructed the occupational exposure
      histories for 595 incident cases of primary exocrinic cancer of the pancreas and
      of 1,622 cancer controls, using three different methods. We found elevated odds
      ratios (OR) for ionizing radiation [OR = 4.3; 95% confidence interval (CI) = 1.6
      11.4], nonchlorinated solvents (OR = 1.6-1.8), and pesticides (OR = 1.7; 95% CI =
      0.8-3.4). Asbestos, chromates, cleaning agents, waxes, polishes, and most other
      exposures were not meaningfully associated with pancreatic cancer. Inorganic dust
      containing crystalline silica (OR = 2.0; 95% CI = 1.2-3.5), heat stress (OR =
      2.2; 95% CI = 0.8-6.6), and rubber chemicals including acrylonitrile (OR = 2.1;
      95% CI = 0.9-4.7) emerged as previously unsuspected risk factors. Occupational
      exposure probably has a small role in the etiology of pancreatic cancer in the
      present-day industrialized or postindustrial work environment.

PMID- 8562626
TI  - An epidemiologic study of bronchial asthma and smoking.
AB  - The role of smoking and air pollution in bronchial asthma in otherwise healthy
      adults is still unclear. We compared 79 cases of asthma, diagnosed between ages
      20 and 65 years, with 304 randomly drawn population controls of similar age from
      the same catchment area as the cases. The comparison involved questionnaire
      information on smoking habits, occupational exposures, dwelling conditions,
      various suspect allergenic exposures, and atopy. Those who had smoked for 3 years
      or more, present or past, were at increased risk for bronchial asthma (odds ratio
      = 1.9; 95% confidence interval = 1.1-3.3). Adjustment by multiple logistic
      regression for age and gender as well as atopy and air pollution at work did not
      change the relative risk estimate. Exposure to environmental tobacco smoke, or
      passive smoking, at work involved a slightly greater risk.

PMID- 8562627
TI  - Changes in dietary fat intake preceding the diagnosis of cancer.
AB  - We studied changes in dietary fat intake preceding the diagnosis of cancer in 96
      men diagnosed with cancer during the Coronary Primary Prevention Trial and Post
      trial Follow-up. Diet was assessed semiannually by 24-hour recall for the
      duration of the trial. Dietary fat intake was elevated in the interval 12-24
      months before diagnosis compared with the interval 24-36 months before diagnosis
      [6.9 gm per day; 95% confidence interval (CI) = 0.04-13.7]. The percentage of
      calories as fat was also elevated (1.9%; 95% CI = 0.34-3.4). Fat consumption
      decreased in the 0- to 12-month prediagnostic interval. The basis for the
      elevation is unclear, but it may have been due to the metabolic effects of cancer
      before its diagnosis. Case-control studies of long-term diet may overestimate
      positive associations between dietary fat and cancer risk if the cases' recall
      includes the prediagnostic period, during which fat intake is elevated. In
      analyses of prospective studies of dietary fat and cancer, data from within the
      first 2-3 years of baseline should be examined separately to evaluate the
      potential for bias introduced by the inclusion of measurements representing
      transient elevations in dietary fat intake.

PMID- 8562628
TI  - Bias in using family history as a risk factor in case-control studies of disease.
AB  - In many case-control studies of common diseases, investigators use family history
      information to assess familial aggregation of the disease and the influence of
      genetic factors. Positive family history among first-degree relatives is often
      used as a risk factor, and its odds ratio is calculated. Although the limitations
      of this approach have been discussed, it is not clear how much impact such
      limitations could have on measuring familial aggregation. To assess this impact,
      we compare odds ratios derived from using a positive family history in case
      control studies with measures of relative risk derived from comparing lifetime
      risks of disease among first-degree relatives of case subjects with those among
      first-degree relatives of control subjects. Positive family history is a function
      of the number of relatives, the background risk of disease, the age distribution
      of relatives, and the correlation in risk among relatives. It can be shown that
      even without case-control differences in the number or ages of relatives,
      positive family history tends to overestimate relative risk measures applied to
      individual relatives. This overestimation is accentuated with increasing
      frequency of the disease, with increasing number of relatives, and for diseases
      with earlier age at onset. It is further affected by even small case-control
      differences in family size and age distribution of relatives. As such, positive
      family history is not a stable indicator of familial aggregation across different
      case-control studies of the same disease.

PMID- 8562629
TI  - Are seasonal preferences in pregnancy planning a source of bias in studies of
      seasonal variation in reproductive outcomes? The European Study Group on
      Infertility and Subfecundity.
AB  - Seasonal variation in reproductive failures is expected, as many of the putative
      causes change over the seasons. Many studies have documented such seasonal
      variation in reproductive failures, but none has addressed the potential source
      of bias related to seasonal planning of pregnancies. Our aim was to quantify this
      bias under realistic assumptions. We used data from the European Study of
      Infertility and Subfecundity, which is a study based upon representative samples
      of women age 25-44 years in different parts of Europe. Data on pregnancy planning
      stem from personal interviews. Altogether, we analyzed 4,731 pregnancies. Results
      show that pregnancy planning is not evenly distributed over the seasons, with
      summer the preferred time for starting pregnancy. The most fecund will conceive
      within the preferred time, but those who are subfecund may not succeed until
      later. Since subfecund women have a higher risk of some reproductive failures
      (spontaneous abortions, for example), the seasonal planning differences could in
      themselves lead to seasonal variations in reproductive failures. A simulation
      model shows that bias related to differential pregnancy planning is likely to
      have only a small impact under the present conditions in Europe.

PMID- 8562630
TI  - Risk factors for preterm delivery in a healthy cohort.
AB  - To examine whether risk factors differed among subgroups of preterm (< 37 weeks
      of gestation) deliveries, we studied a cohort of 1,825 enlisted servicewomen who
      delivered from 1987 through 1990 at four U.S. Army medical centers. Preterm
      deliveries were classified by length of gestation (< 29 weeks, 29-32 weeks, 33-36
      weeks) and clinical course [medical indication, idiopathic preterm labor, or
      preterm rupture of membranes (PROM)]. We abstracted medical records for
      information on age, race, army rank, marital status, gravidity, parity, the
      baby's sex, maternal prepregnancy height and weight, gestation at entry to
      prenatal care, alcohol drinking and smoking, time since and outcome of preceding
      pregnancy, surgery performed during pregnancy, anemia, and diagnoses of uterine
      abnormalities, sexually transmitted diseases, and urinary tract infections. We
      used proportional hazards analysis to evaluate associations for each subgroup of
      preterm delivery. The relative odds associated with a history of preterm delivery
      in the preceding pregnancy ranged from 3.1 for deliveries due to preterm labor or
      PROM to 6.2 for deliveries that occurred during 29-32 weeks; none of the other
      factors was consistently associated across the subgroups of preterm delivery. The
      paucity of associations is consistent with the conclusion of other investigators
      that most of the causes of preterm delivery are unknown.

PMID- 8562631
TI  - Bias in studies of preterm and postterm delivery due to ultrasound assessment of
      gestational age.
AB  - Ultrasound measurement of fetal dimensions is widely used for estimating
      gestational age. A little-discussed limitation of this method is that variations
      in fetal size at a given stage of pregnancy are converted to differences in
      gestational age. Factors that affect pregnancy duration often affect fetal size
      also. We explore how the effect of such factors may be biased when gestational
      age is determined by ultrasound. We selected 3,606 women with singleton
      pregnancies (1989-1991) who had an early ultrasound measurement of fetal
      biparietal diameter (BPD) and a good-quality history of last menstrual period
      (LMP). Using the two measures of gestational age, we estimated risk of preterm
      and postterm delivery for female babies vs males and for smoking women vs
      nonsmoking women. There was a 13% excess of preterm delivery among female babies
      when gestational age was determined by ultrasound, but no excess when gestational
      age was defined by LMP. For postterm delivery, female babies had a 19% lower risk
      with ultrasound-defined age, but no deficit with LMP-defined age. We found a
      similar bias with ultrasound in the analysis of maternal smoking. Thus, factors
      that reduce fetal size inflate the risk of preterm delivery and deflate the risk
      of postterm delivery when gestational age is based on ultrasound measurement of
      the fetus. This bias can distort the relative risk of preterm or postterm
      delivery by 10-20%.

PMID- 8562632
TI  - Cutaneous melanoma in women. V. Characteristics of those who tan and those who
      burn when exposed to summer sun.
AB  - We studied 338 Caucasian women with superficial spreading melanoma (hereafter
      called melanoma) and 872 control subjects ages 25-59 years and compared
      characteristics of women who reported that they tanned with sun exposure with
      those who reported that they burned. The purpose of the study was to investigate
      how skin type, as measured by tendency to burn or tan, modified the effect of
      other melanoma risk factors. There was a clear relation between tendency to burn
      and prevalence of red hair, light complexion, freckles, and history of sunburns
      during elementary school and high school. Host factors such as light complexion
      and increased number of self-assessed large nevi elevated risk of melanoma among
      women of all skin types. Increased risk for melanoma associated with frequent
      sunburns during childhood and adolescence was most pronounced for women who
      burned and then tanned; risk was not substantially elevated for women who burned
      without tanning. Women who had a history of sunburns had an increased melanoma
      risk even if they reported tanning.

PMID- 8562633
TI  - Breast cancer among women exposed to polybrominated biphenyls.
AB  - We conducted a nested case-control study with 1,925 women enrolled in a
      polybrominated biphenyl (PBB) registry to examine the association between breast
      cancer and serum PBBs. Twenty women who developed breast cancer were matched to
      290 control subjects on sex, race, and age. Women with serum PBB levels of 2.0
      3.0 parts per billion (ppb) [odds ratio (OR) = 3.5; 95% confidence interval (CI)
      = 0.9-13] or 4.0 ppb or greater (OR = 3.1; 95% CI = 0.8-12) had a higher
      estimated risk for breast cancer than women with less than 2.0 ppb. The odds
      ratios were unchanged when available breast cancer risk factors were included in
      the analysis.

PMID- 8562634
TI  - Application of a method for estimating day of ovulation using urinary estrogen
      and progesterone metabolites.
AB  - Longitudinal epidemiologic studies of menstrual and reproductive function are
      more informative if one can identify day of ovulation. We previously developed a
      method for estimating day of ovulation that is feasible for epidemiologic
      studies. The method relies on the relative concentrations of estrogen and
      progesterone metabolites in daily first-morning urine specimens and does not
      require creatinine adjustment. This paper describes results of applying this
      method to a large study with 724 menstrual cycles from 217 women. The method
      estimated a credible day of ovulation in 88% of cycles. Missing data accounted
      for most of the failures. When we excluded anovulatory cycles (1%) and cycles
      with missing data, the method estimated a day of ovulation in 97% of cycles.
      Variance in luteal phase length was small for our sample, suggesting that this
      method of identifying a day of ovulation introduces no more measurement error
      than when day of ovulation is determined by plasma luteinizing hormone (LH), the
      standard clinical method.

PMID- 8562635
TI  - Estimation of exposure prevalence in a population at risk using data from cases
      and an external estimate of the relative risk.
AB  - An estimate of exposure prevalence is often of interest, for example when
      targeting public health interventions. Unfortunately, this information may not be
      available from field studies. In this paper, I propose a method to estimate
      exposure prevalence when data are available only from a series of cases and an
      estimate of the relative risk for the exposure is available from published
      studies. The method is most useful when (1) the prevalence of exposure in the
      case series is a valid estimate of exposure prevalence among cases in the study
      base, and (2) the external estimate of relative risk is unbiased and can be
      generalized to the study base. I recommend that a sensitivity analysis be done
      when either condition 1 or 2 above is not met with certainty. I illustrate the
      method to estimate the prevalence of aspirin use in a population at risk for
      myocardial infarction using data from 1,228 cases and an estimate of the relative
      risk for the effect of aspirin use from a published meta-analysis.

PMID- 8562636
TI  - Calcium, dairy products, and the risk of hip fracture in women in northern Italy.
AB  - We report the relation between hip fracture and intake of calcium and dairy
      products in postmenopausal women age 45 years or over. We conducted a case
      control study in northern Italy. We interviewed a total of 241 cases of hip
      fracture and 719 controls in hospital for acute, nonneoplastic, nontraumatic,
      nondigestive, non-hormone-related diseases during their hospital stay. We derived
      odds ratios (OR) and their 95% confidence intervals (CI), according to intake of
      calcium, milk, and cheese from multiple logistic regression equations, including
      terms for age, education, body mass index, smoking status, alcohol drinking, and
      estrogen replacement therapy. Cutoff points for extreme quintiles of calcium
      intake were 443 and 1,026 mg per day. Compared with the lowest quintile of
      calcium intake, the multivariate ORs were 1.2 (95% CI = 0.7-2.0), 1.1 (95% CI =
      0.6-1.7), 1.1 (95% CI = 0.6-1.7), and 1.2 (95% CI = 0.8-2.0) for subsequent
      quintiles of intake. Similarly, there was no appreciable association with milk
      (compared with less than 7 drinks per week, ORs were 1.2 and 1.0, respectively,
      for 7 and more than 7 drinks per week) or cheese intake (compared with less than
      4 portions per week, ORs were 1.2 for 4-6 portions and 1.0 for more than 6
      portions per week). OR estimates for calcium intake (tertiles) were consistent
      across strata of age, education, smoking status, and alcohol drinking. Thus,
      within the range of variation of intake of the main sources of calcium in this
      population, there was little association between hip fractures in women and
      intake of calcium, milk, and cheese.

PMID- 8562637
TI  - Biased comparisons of lung cancer survival across geographic areas: effects of
      stage bias.
AB  - This report illustrates bias that may affect comparative analyses of cancer
      survival across geographic areas and describes how it limits the conclusions that
      can be drawn from such data. Despite the application of a standardized procedure
      for assigning tumor stage, patients from different areas who are assigned the
      same stage category may not be homogeneous with respect to extent of disease, if
      staging is accomplished more aggressively in one group than in another. Stage
      specific comparisons of survival may be biased as a result. Cancer sites for
      which a large majority of patients are treated surgically may be less susceptible
      to stage bias.

PMID- 8562638
TI  - Molecular epidemiology: collision of two cultures.

PMID- 8562639
TI  - Problems in the average-risk interpretation of categorical dose-response
      analyses.

PMID- 8562640
TI  - On the need for ethics curricula in epidemiology.

PMID- 8562641
TI  - Printed signatures and response rates.

PMID- 8562642
TI  - Capture-recapture estimation.

PMID- 8562643
TI  - Maternal smoking, alcohol consumption, and fetal growth.

PMID- 8562644
TI  - Odds and odds ratio: an odd confusion.

PMID- 8562645
TI  - [A method of selective PCR-amplification of genomic DNA fragments (SAGF method)].
AB  - A method for separating into definite sets of a complex mixture of fragments
      obtained by DNA cleavage with IIS- or IIN-types of restriction endonucleases
      producing single-stranded termini of different sequences at the fragment ends has
      been developed. The method is based on the ligation of short double-stranded
      adapters with single-stranded termini complementary to the termini of a selected
      set of fragments followed by PCR-amplification with the primer which represents a
      strand of the adapters. Using endonucleases BcoKI and Bli7361 recognizing
      sequences CTCTTC and GGTCTC and producing three- and four-nucleotide 5'-termini,
      respectively, it has been shown that amplification of a set of fragments occurs
      only when the adapters are attached to DNA fragments with DNA-ligase. Several
      applications of the SAGF-method are suggested: for obtaining individual bands in
      DNA fingerprinting; for reducing the kinetic complexity of DNA in the
      representational difference analysis (RDA method) of complex genomes; for
      cataloguing DNA fragments, and for constructing physical genomic maps.

PMID- 8562646
TI  - [Role of cholesterol esters in triglyceride transport].
AB  - Biosynthesis of cholesterol esters in the blood flow and their function are
      determined by the fact that these compounds are the sole endogenously synthesized
      molecules whose hydrophobicity is higher than that of triglycerides transferred
      by the blood. Within the structure of intermediate density lipoproteins,
      cholesterol esters substitute for triglycerides during association of apoprotein
      B-100 with the C-terminal lipid-binding domain. Substitution of the liquid
      crystalline phase of triglycerides for the corresponding phase of cholesterol
      esters results in a significant alteration of the apoprotein B-100 conformation
      and the formation of low density lipoproteins. Within the structure of low
      density lipoproteins, the N-terminal domain (apoprotein B-100 ligand) acquires an
      active conformation and an ability to interact with cell membrane receptors,
      thereby facilitating their absorption of low density lipoproteins. Cholesterol
      synthesis in the blood is an independent step in triglyceride transport.
      Inhibition of cholesterol ester synthesis into high density lipoproteins and
      their conversion into intermediate density lipoproteins is unaccompanied by the
      acquisition by apoprotein B-100 of a final conformation or by the formation of
      low density lipoproteins. Remnants of intermediate density lipoproteins having an
      intermediate conformation of apoprotein B-100 and the inactive position of the
      domain ligand are accumulated in the blood. This results in the development of
      IIb type hyperlipoproteinemia. Resumption of conversion of cholesterol esters
      from high density lipoproteins into intermediate density lipoprotein remnants
      normalizes the triglyceride transport. The final conformation of apoprotein B-100
      can be modelled by substituting triglycerides in intermediate density lipoprotein
      remnants for another substance whose hydrophobicity is similar to that of
      cholesterol esters (dolichol, probucol).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562647
TI  - [Interaction of cytokines with cellular receptors].
AB  - The cytokinin family includes biologically active polypeptide molecules secreted
      by haemopoietic and immunocompetent cells which control cell proliferation and
      differentiation. Cytokinin interactions with specific receptors of the cell
      surface results in oligomerization of these receptors, i.e. in association of two
      or more membrane molecules. It is becoming obvious that oligomerization of
      receptors is an indispensable stage in the manifestation by cytokinins of their
      biological activity. In this context, studies of regularities of cytokinin
      receptor interactions resulting in receptor oligomerization is important for both
      elucidation of molecular mechanisms underlying kinin action and construction of
      compounds having the properties of agonists (or antagonists) of cytokinin-induced
      oligomerization of membrane receptors. A conclusion is draw about the important
      role of polyvalent cytokinin interactions with cell receptors in the initiation
      of oligomerization and subsequent formation of functionally active receptor
      complex.

PMID- 8562648
TI  - [Organelle specificity of yeast cell polyphosphatases].
AB  - The properties of purified cell envelope polyphosphatase, polyphosphatase
      activities of vacuoles and cytosol fractions of the Saccharomyces cerevisiae
      yeast have been compared. The whole body of evidence presently available suggest
      that each of the compartments under study is equipped with its own
      polyphosphatase which differs from polyphosphatases of other organelles. It is
      proposed that the organelle specificity of yeast polyphosphatases may reflect the
      endosymbiotic origin of eucaryotic cells.

PMID- 8562649
TI  - [Recombinant human lymphotoxin: synthesis in Escherichia coli cells,
      purification, and certain properties].
AB  - The biosynthesis of recombinant human lymphotoxin produced by E. coli
      SG20050/pLT21 cells and deprived of 21 amino acid residues has been studied. It
      has been shown that the bulk of the recombinant protein in E. coli cells is in
      the soluble form and predominantly localized in the cytoplasm. The maximal
      synthesis of soluble recombinant lymphotoxin is achieved during 24-hour
      cultivation of producing strain cells at 32 degrees C. A procedure for isolation
      and purification of the recombinant protein from E. coli cells has been
      developed. The purification is accomplished by gel-filtration on Sephadex G-150,
      ion-exchange chromatography on DEAE-Sephadex and CM-Sephadex, resulting in 97
      fold purification and a 62% yield. The specific activity of the protein is about
      1-10(8) U per mg of protein. Some physico-chemical properties of the recombinant
      protein have been studied.

PMID- 8562650
TI  - [Interaction of hypochlorite with hydroperoxides and other oxidation products of
      phosphatidylcholine liposomes].
AB  - The chemiluminescence in the presence of luminol has been used to measure the
      amount of hypochlorite and its reduction during the interaction with oxidized and
      non-oxidized liposomes from egg yolk phosphatidylcholine as well as with organic
      peroxides (tert-butylhydroperoxide, cumene hydroperoxide, di-tert-butylperoxide,
      tert-butylperbenzoate, di-benzoylperoxide), and epoxides (cis- and trans-2,3
      epoxy-butane, cholesterol-5 alpha,6 alpha-epoxide, and cis-9,10-epoxystearic
      acid). Since hypochlorite did not react with the saturated phospholipid,
      dimyristoylphosphatidylcholine (DMPC), and the reduction of double bonds in egg
      yolk phosphatidylcholine liposomes occurred at the same rate in both oxidized and
      non-oxidized liposomes, it may be suggested that hypochlorite interacted
      precisely with LPO products. None of the epoxides tested in this study, similar
      to di-tert-butylperoxide, tert-butylperbenzoate, di-benzoylperoxide, incorporated
      into liposomes reacted with hypochlorite. In contrast, tert-butylhydroperoxide
      and cumene hydroperoxide effectively reacted with it. The data obtained suggest
      that epoxides, dialkyl-, diacyl-, and alkyl-acyl-peroxides are not involved in
      hypochlorite-induced LPO. At the same time, organic hydroperoxides commonly
      present in certain amounts in the biomembrane lipid phase in vivo may play a role
      lf an intermediate; its interaction with HOCl/OCl- gives rise to free radical
      formation followed by accumulation of LPO products.

PMID- 8562651
TI  - [Analysis of amino acid sequences of Rhodobacter sphaeroides glutamine
      synthetase].
AB  - A comparative analysis of the amino acid sequence of glutamine synthetase (GS) of
      the photosynthetic purple bacterium Rhodobacter sphaeroides revealed that the
      enzyme is typical for first type procaryotic GSs and structurally resembles GSs
      of enteric bacteria. The data obtained indicate that the complex phenotype of
      purple bacterial mutants at the glnA gene coding for GS may be conditioned by
      specific regulation of nitrogen metabolism in bacterial cells rather than by
      structural-and-functional peculiarities of GS.

PMID- 8562652
TI  - [Site-specific endonuclease and methylase from thermophilic bacteria of Bacillus
      species IS4].
AB  - The site-specific endonuclease R . BspIS4I and methylase M . BspIS4I have been
      isolated and purified to functional purity from the thermophilic strain of
      Bacillus species IS4. R . BspIS4I recognizes sequence [sequence: see text] on the
      DNA and cleaves it as indicated by the arrows to form single-stranded 4
      nucleotide 5'-protruding termini. The enzyme is an isoschizomer of BbvII. M .
      BspIS4I is related to adenine-specific methylase.

PMID- 8562653
TI  - [Kinetic uniformity of the ATP hydrolysis reaction catalyzed by Mg2+-ATPase in
      smooth muscle cell membrane].
AB  - The kinetic properties of Mg(2+)-ATPase (EC 3.6.1.3) from myometrium cell plasma
      membranes have been studied. Under conditions of enzyme saturation with ATP (0.5
      1.0 mM) or Mg2+ (1.0-5.0 mM) the initial maximal rates of the Mg(2+)-dependent
      enzymatic ATP hydrolysis, V0 ATP and V0 Mg, are 27.4 +/- 3.3 and 25.2 +/- 4.1
      mumol Pi/hour/mg of protein, respectively. The apparent Michaelis constant, Km,
      for ATP and of the apparent activation constant, K alpha, for Mg2+ are equal to
      28.1 +/- 2.6 and 107.0 +/- 26.0 microM, respectively. The bivalent metal ions
      used at 1.0 mM suppress the Mg(2+)-dependent hydrolysis of ATP whose efficiency
      decreases in the following order: Cu2+ > Zn2+ = Ni2+ > Mn2+ > Ca2+ > Co2+.
      Alkalinization of the incubation medium from pH 6.0 to pH 8.0 stimulates the
      Mg(2+)-dependent hydrolysis of ATP. It has been found that Mg(2+)-ATPase has the
      properties of an H(+)-sensitive enzymatic sensor which is characterized by a
      linear dependence between the initial maximal rate of the reaction, V0, and the
      pH value. The feasible role of plasma membrane Mg(2+)-ATPase in some reactions
      responsible for the control of proton and Ca2+ homeostasis in myometrium cells
      has been investigated.

PMID- 8562654
TI  - [A new activator of soluble guanylate cyclase generated by nitric oxide and
      having antihypertensive and anti-aggregation properties].
AB  - The effects of aminoethylisothiuronium bromide known as a radioprotector on the
      activity of human platelet soluble guanylate cyclase and on ADP-induced
      aggregation of human platelets have been studied. It has been shown that in Tris
      buffer and at definite pH values aminoethylisothiuronium bromide is converted
      into mercaptoethylguanidine as a result of a transguanidine rearrangement. The
      latter contains in its molecule both guanidine and SH-groups which appear to be
      the donor and acceptor of nitric oxide, respectively. It was found that after its
      rearrangement into mercaptoethylguanidine, aminoethylisothiuronium bromide
      activates human platelet soluble guanylate cyclase, inhibits ADP-induced
      aggregation of human platelets and accelerates their spontaneous disaggregation.
      The stimulating effect of aminoethylisothiuronium bromide depends on the
      effectiveness of its transguanidine rearrangement into mercaptoethylguanidine. A
      molecular mechanism of the hypotensive side effect of aminoethylisothiuronium
      bromide is proposed.

PMID- 8562655
TI  - [Modulation of Na+,K+-pump activity and Na+,Li+-exchange in rabbit erythrocytes
      at various stages of cholesterol feeding].
AB  - The activities of the Na+,K(+)-pump and the Na+/Li(+)-exchange and the
      intracellular concentration of Na+ in erythrocytes of rabbits with experimental
      hypercholesterolemia have been studied at different stages of cholesterol (Ch)
      feeding as well as at different intervals after stopping of cholesterol-rich
      diets. After sufficiently long periods of feeding the animals with Ch (1.5-2
      months), a significant activation of the Na+,K(+)-pump, reduction of the
      Na+/Li(+)-exchange rate and lowering of the intracellular sodium content in
      erythrocytes of rabbits from experimental groups were observed. Several months
      after stopping Ch-rich diets there was a partial normalization of the parameters
      under study. However, at the initial stage of the experiment (20 days after the
      beginning of Ch feeding) as well as two weeks after Ch feeding had been stopped,
      there occurred no changes in the activities of the ion transport systems or in
      [Na+]i despite substantial changes in the plasma Ch level. It is suggested that
      the observed effect of dietary Ch on the activity of ion carriers may be mediated
      by affecting the expression of the corresponding genes.

PMID- 8562656
TI  - [Low concentrations of cyclosporin A close Ca2+-dependent inner mitochondrial
      membrane pores in the absence of other effectors].
AB  - Earlier it has been demonstrated that the recoupling action of cyclosporin A on
      mitochondria deenergized by the opening of the Ca(+)-dependent pore requires
      higher cyclosporin A concentrations than those, which are necessary for
      preventing the permeabilization as well as the presence of additional effectors,
      such as adenine nucleotides and Mg2+. It has been shown that cyclosporin A
      reseals the pore and prevents its opening when used at the same low
      concentrations (0.1-0.4 microM), while its higher concentrations (0.5-1.0 microM)
      produce the recoupling of mitochondria. In contrast with recoupling, resealing of
      the pore by cyclosporin A does not require Mg2+ or adenine nucleotides.
      Carboxyatractylate which reverses the cyclosporin A-induced restoration of the
      membrane potential does not induce repeated opening of the pore. The
      carboxyatractylate-induced depolarization of the inner mitochondrial membrane is
      sensitive to ruthenium red. Besides, ruthenium red restores the recoupling action
      of cyclosporin A in the absence of carboxyatractylate. The data obtained suggest
      that the loss by cyclosporin A of its recoupling potency may result from the
      induction of the Ca2+/2H+ antiporter. Induction of the Ca2+/2H+ antiporter in
      combination with a ruthenium red-sensitive Ca2+ uniporter provides the uncoupling
      mitochondria even with a closed Ca(2+)-dependent pore. Apparently, Ca2+/2H+
      antiporter induction is a result of inhibition of the ADP/ATP antiporter by a
      natural or exogenous inhibitor. This process seems to require a preliminary
      release of certain protective factors from the mitochondrial matrix.

PMID- 8562657
TI  - [Modulation of the antitumor activity of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl
      3-(2-chloroethyl)-3-nitrosoure a by O(6)-methyl-2'-deoxyguanosine--a new
      inhibitor of O(6)-alkylguanine-DNA-alkyltransferase].
AB  - O6-Methyl-2'-deoxyguanosine (O6-MedG), a novel inhibitor of O6-alkylguanine-DNA
      alkyltransferase (O6-AGT), has been synthesized. The ability of O6-MedG to
      deplete the O6-AGT activity in leukemia L1210 and melanoma B16 cells in vivo has
      been studied. After intraperitoneal administration of O6-MedG to mice bearing
      leukemia L1210 or melanoma B16, the activity of O6-AGT in tumour cells decreased
      by 50%. Pretreatment of leukemia L1210 bearing mice with O6-MedG (200 mg/kg) 24
      hours prior to ACNU (15 mg/kg) administration resulted in six out of seven 60-day
      survivors. Treatment of mice with ACNU (15 mg/kg) alone increased the life span
      by 200%. Treatment of melanoma B16 bearing mice with O6-MedG and 3 hours
      thereafter with ACNU resulted in a 50% inhibition of tumour growth, whereas the
      inhibiting effect of ACNU alone was 16%. There was no difference in leukemia
      growth when L1210/BCNU bearing mice were treated with O6-MedG followed by ACNU
      treatment. In vivo ACNU (15 mg/kg) produced a deep and prolonged inhibition of
      DNA, RNA and protein synthesis in leukemia L1210 cells. The DNA synthesis in
      leukemia L1210/BCNU cells was shown to recover more rapidly than in L1210 cells.
      The activities of DNA-polymerases alpha and beta and, especially, of O6-AGT were
      elevated in ACNU-resistant leukemia cells as compared with ACNU-sensitive cells.
      The activation of some repairing enzymes, such as O6-AGT, DNA-polymerases alpha
      and beta as well as increased levels of GSH may play a role in the development of
      drug resistance to ACNU.

PMID- 8562658
TI  - [Inhibition of exogenous serine proteinases by a trypsin inhibitor from the
      buckwheat IT-1 seeds].
AB  - The possibility of inhibition of exogenous trypsin- and chymotrypsin-like
      proteinases by a proteinase inhibitor from buckwheat (IT-1) seeds has been
      studied. The inhibition constants for bovine trypsin and alpha-chymotrypsin and
      human granulocyte cathepsin G by IT-1 are equal to 1.1, 67 and 200 nm,
      respectively. The specificity of IT-1 with regard to its primary sequence
      adjacent to the active center and to its homology with inhibitors pertaining to
      the potato inhibitor I family has been carried out. It is concluded that by
      virtue of the basic nature of the P1 (Arg) residue in the active center IT-1 is
      not capable to bind human granulocyte elastase.

PMID- 8562659
TI  - [Paradoxes of cerebral oxidative metabolism].
AB  - The free radical forms of oxygen resulting from disorders in brain blood supply
      and accumulated by subsequent reperfusion modify neuron metabolism in two
      different ways. On the one hand, free oxygen radicals activate the breakdown and
      destruction of neuronal membranes caused by ischemia and provide the oxidative
      attack at the key neuronal receptors and enzymes involved in excitation. On the
      other hand, they can play a role of specific messengers regulating vasodilation
      and adjusting neurons to the changed conditions of functioning. As a consequence,
      the antioxidant protection of the brain provided by hydrophobic antioxidants
      characterized by a lag period appears to be less effective than the protective
      effect of natural hydrophilic antioxidants having a direct action.

PMID- 8562660
TI  - The study of paranoia and suspiciousness.

PMID- 8562661
TI  - Psychiatric status after human fetal mesencephalic tissue transplantation in
      Parkinson's disease.
AB  - This report describes the prospective and systematic psychiatric assessment of
      nine patients who received transplantation of human fetal mesencephalic tissue
      into the caudate nucleus for treatment of Parkinson's disease. Unlike adrenal
      medullary transplantation, which often causes psychosis or delirium, this
      procedure appeared to have few perioperative sequelae. On longer-term follow-up,
      there was some statistical evidence of deterioration in psychiatric status, as
      manifested primarily in depressive and nonspecific emotional and behavioral
      symptoms. This group effect was partly attributable to the occurrence of discrete
      episodes of illness (major depression and panic disorder with agoraphobia) in
      some patients, but it was unclear whether such episodes occurred more often than
      would ordinarily be expected in Parkinson's disease. Differences in the
      neurobiological effects of fetal mesencephalic and adrenal medullary grafts may
      account for differences in the psychiatric sequelae of patients receiving these
      procedures.

PMID- 8562662
TI  - Electroencephalographic sleep profiles in single-episode and recurrent unipolar
      forms of major depression: I. Comparison during acute depressive states.
AB  - The current study was conducted to examine if recurrent depression is associated
      with more severe disturbances of all-night EEG sleep profiles than single-episode
      depressions. Unmedicated sex- and age-matched groups of 22 single-episode (SE)
      and 44 recurrent unipolar (RU) outpatients with DSM-III-R/SADS/RDC major
      depression underwent 2 consecutive nights of EEG sleep recording. Multivariate
      analyses of covariance (MANCOVAs) and/or analyses of covariance (ANCOVAs) were
      performed on six sets of sleep measures. Recurrent unipolar depression was
      associated with significantly increased phasic REM sleep, as well as increased
      REM counts on the second night of study. Recurrent depression also was associated
      with significantly poorer sleep efficiency, although the groups did not show
      consistent differences in sleep architecture or slow-wave sleep. Our findings
      generally support the hypothesis that recurrent depression is associated with a
      more severe neurophysiologic substrate than phenotypically similar SE cases.
      Results are, for the most part, compatible with Post's (1992) model of illness
      progression, particularly with respect to greater disturbances of state-dependent
      sleep abnormalities in the RU cases. Longitudinal studies are needed to confirm
      the evolution of such changes prospectively.

PMID- 8562663
TI  - The relationship of minor physical anomalies and other putative indices of
      developmental disturbance in schizophrenia to abnormalities of cerebral structure
      on magnetic resonance imaging.
AB  - Minor physical anomalies, together with obstetric complications, family history,
      and handedness status, were assessed to explore putative neurodevelopmental
      disturbance(s) in patients with schizophrenia whose cerebral structure had been
      examined previously by magnetic resonance imaging. Minor physical anomalies were
      related to negative symptoms in males and to premorbid intellectual function in
      females, but not to ventricular volume; however, three patients with evident
      neurodevelopmental anomalies of the ventricular system showed prominent minor
      physical anomalies. In exploratory analyses, obstetric complications were
      associated with left ventricular asymmetry, and a positive family history with
      inverse profiles of asymmetry in males vs. females; non-right-handedness was
      associated with increased ventricular volume in males but with poorer premorbid
      intellectual function in females. This nexus of relationships and their gender
      specificities suggest early dysmorphogenesis in schizophrenia that is related to
      sexual dimorphism.

PMID- 8562664
TI  - Effects of acute intravenous clomipramine on obsessive-compulsive symptoms and
      response to chronic treatment.
AB  - The aim of this study was to test the hypothesis that obsessive-compulsive
      symptoms are temporarily worsened by acute intravenous clomipramine, suggesting
      that there is a basal hypersensitivity of serotonin (5-HT) receptors in obsessive
      compulsive (OC) patients. We also investigated the relationship of the effects of
      acute (intravenous) and chronic (oral) administration of clomipramine. Twenty
      eight OC patients were recruited. The first part of the study included placebo
      and clomipramine infusions and monitoring of OC symptoms by 100 mm Visual
      Analogue self-rated scales (VAS). There was significant worsening of obsessions
      in the whole sample during clomipramine infusion. The second part included
      standardized 10-week oral treatments with clomipramine and evaluation of clinical
      efficacy. Among the 18 patients who completed the second part of the study, oral
      clomipramine significantly reduced OC symptoms, but OC patients who had become
      worse after clomipramine infusion showed higher Y-BOCS scores.

PMID- 8562665
TI  - Oral physostigmine in Alzheimer's disease: effects on norepinephrine and
      vasopressin in cerebrospinal fluid and plasma.
AB  - Physostigmine is a cholinesterase inhibitor which enhances central and peripheral
      cholinergic activity. In this study, we explored in persons with Alzheimer's
      disease (AD) the effects of an acute dose of physostigmine in patients receiving
      chronic physostigmine treatment on the activity of the cholinergically regulated
      noradrenergic and arginine vasopressin (AVP) systems. Specifically, we estimated
      the effects of sustained release oral physostigmine on central and peripheral
      noradrenergic and AVP systems by measuring norepinephrine (NE) and AVP in
      cerebrospinal fluid (CSF) and plasma. Lumbar punctures were performed in both
      physostigmine and no drug treatment conditions. In some subjects the effects of
      physostigmine on the plasma AVP response to the osmolar stimulus of a hypertonic
      saline infusion also were measured. NE concentrations in both CSF and plasma were
      significantly lower in the physostigmine than in the no drug condition. AVP
      concentrations did not differ between conditions in either compartment, nor did
      physostigmine affect the AVP response to hypertonic saline. Physostigmine appears
      to decrease both central and peripheral noradrenergic activity in AD.

PMID- 8562666
TI  - Delayed startle sensitization distinguishes rats exposed to one or three stress
      sessions: further evidence toward an animal model of PTSD.
AB  - Posttraumatic stress disorder (PTSD) may occur in humans exposed chronically to
      stressors or after a single exposure to a traumatic event. A distinguishing
      feature of patients with PTSD is an exaggerated startle response, evident long
      after the traumatic event. We have observed similar abnormalities in our animal
      model of a chronic stress state. Rats exposed to 3 days (3DS) of our stress
      regimen (2-hr sessions of 40, 2 mA tailshocks) have exhibited a consistent
      pattern of persistent physiological and behavioral abnormalities including an
      exaggerated startle response several days after stressor cessation. In contrast,
      rats exposed to a single stress session (1DS) have exhibited many, but not all,
      of the persistent abnormalities displayed by 3DS rats. The present experiment
      compared the startle responding of 3DS and 1DS rats 4, 7, and 10 days after
      stressor cessation. Consistent with previous work, stressed rats exhibited
      elevated basal plasma corticosterone (CORT) levels the first day poststressor.
      These CORT levels were sensitive to the number of stressor exposures with higher
      CORT levels in 3DS rats than in 1DS rats. As for startle responding, the 1DS rats
      exhibited an exaggerated startle response 7 days poststressor, whereas startle
      sensitization was apparent 10 days poststressor in 3DS rats. Thus, the appearance
      of an exaggerated startle response after stressor cessation appears to be related
      to the number of stress session exposures. These animal models, the 3DS and 1DS
      rats, may be useful to gain insight into the neurobehavioral changes associated
      with PTSD.

PMID- 8562667
TI  - Salivary cortisol responses and the risk for substance abuse in prepubertal boys.
AB  - Investigations of adults with a psychoactive substance use disorder (PSUD) or
      antisocial behavior have reported diminished secretion of the adrenal "stress"
      hormone, cortisol. Consequently, we determined whether prepubertal sons of PSUD
      fathers, at high risk for later PSUD, differed from controls on salivary cortisol
      concentrations before, and after, an anticipated stressor. The roles of
      problematic behavioral disposition and state anxiety in the cortisol responses
      were also examined. A significant risk-group x time interaction for salivary
      cortisol concentrations was found, with high-risk boys secreting less salivary
      cortisol than controls when anticipating the task. High-risk boys also had
      significantly higher scores for aggressive delinquency and impulsivity that
      wholly accounted for the risk-group x time effect on salivary cortisol. Thus,
      cortisol hyporesponsivity was associated with the dysregulated behaviors
      prevalent among high-risk boys. The results suggest that cortisol
      hyporesponsivity could be a "marker" for later antisociality and PSUD.

PMID- 8562668
TI  - Fluoxetine and visual hallucinations in dementia.

PMID- 8562669
TI  - Sodium lactate infusion in fibromyalgia patients.

PMID- 8562670
TI  - Ethics for the Society of Biological Psychiatry.

PMID- 8562671
TI  - Hemoconcentration and stress: a review of physiological mechanisms and relevance
      for cardiovascular disease risk.
AB  - Elevated levels of hematocrit and hemoglobin have been identified as an
      independent risk factor for the development of a number of diseases, including
      hypertension, coronary heart disease, and stroke. A growing body of evidence also
      indicates that elevations in hematocrit and hemoglobin are present in situations
      involving both physical and mental stressors. This paper reviews the evidence
      linking decreases in plasma volume causing hemoconcentration with hemodynamic
      adjustments associated with activation of the sympathetic nervous system, and the
      potential relevance of stress-induced hemoconcentration in triggering deleterious
      cardiovascular events. The importance of blood viscosity in understanding the
      effects of hemoconcentration is discussed, along with the need to evaluate the
      degree of hemoconcentration during stress for accurate interpretation of changes
      in certain blood constituents.

PMID- 8562672
TI  - When global information and local information collide: a brain potential analysis
      of the locus of interference effects.
AB  - The objective of the current experiment was to perform a psychophysiological
      investigation of the interference effects of global information on the analysis
      of local information, and vice versa. Subjects' choice reactions to letters at
      one level of information in a compound letter stimulus were impaired when letters
      at the other (irrelevant) level signified the opposite response. In the absence
      of differences in processing speed, global and local information produced
      symmetrical interference effects. Interference effects did vary, however, as a
      function of temporal advantage for the processing of information from either
      level. The individually faster level (be it global or local) interfered with the
      slower level but was itself relatively immune to such interference by the slower
      level. Analysis of event-related brain potentials and of the electromyogram
      revealed that incongruent irrelevant letters induced perceptual conflict but not
      response competition, thus pointing to a perceptual locus of processing dominance
      for the faster processed level of information in the compound stimulus.

PMID- 8562673
TI  - Effects of alcohol on the sleep-stage structure of a nap in the afternoon.
AB  - The effects of the ingestion of 0.8 ml/kg alcohol on the sleep-stage structure of
      nap sleep were compared with those of a non-alcoholic drink in 8 young male
      subjects napping between 14.00 h and 15.00 h. During nights immediately preceding
      experimental sessions, time to bed and time in bed (hence, sleep duration) were
      controlled. While not affecting total nap sleep duration, alcohol significantly
      increased time in stage 4 sleep, primarily at the expense of time in stage 2.

PMID- 8562674
TI  - Spectral analysis of EEG from families.
AB  - Electroencephalographic (EEG) activity was obtained under eyes open and eyes
      closed conditions from ten families, each consisting of a biologically related
      father, mother and two children. Spectral power (microV2) and mean frequency (Hz)
      measures from the delta, theta, alpha-1, alpha-2, beta-1, and beta-2 bands were
      computed for each family member. Non-family controls were constructed from the
      real family data by randomly pairing non-related individuals with one another,
      and correlations between the analogous individuals were also computed. The
      correlations for spectral power between family groups were greater than those
      obtained from the non-families for theta, alpha, and beta band power. The
      correlations for mean frequency between family members were greater than those of
      the non-families for the delta, theta, and alpha bands, although these were not
      as robust as the spectral power findings. In general, few family membership
      effects were found for the eyes open/closed or electrode site conditions. The
      results support findings from twin studies that suggest EEG characteristics are
      determined at least in part by genetic factors.

PMID- 8562675
TI  - The relationship between habitual anger coping style and serum lipid and
      lipoprotein concentrations.
AB  - The relationship between habitual anger coping styles, especially anger
      expression in a socially assertive manner and serum lipid concentrations was
      examined in 86 healthy subjects. Habitual anger expression was measured by the
      Muller Anger Coping Questionnaire (MAQ) on four scales: Aggression, Controlled
      Affect, Guilt, and Social Inhibition. A positive correlation between serum
      cholesterol and Aggression was found, as was a negative correlation between
      LDL/HDL ratio and Controlled Affect. These correlations remained significant
      after adjustments for age, Body Mass Index (BMI), athletic activity, alcohol,
      nicotine and coffee consumption. After these adjustments, significant negative
      partial correlations between Controlled Affect and both total cholesterol and LDL
      were also found. We found no significant gender differences on any lipid measure.
      This study demonstrated that unfavourable lipid profiles are linked to a
      predominantly aggressive anger coping style, whereas favourable lipid profiles
      are associated with more socially assertive anger coping (Controlled Affect).
      Thus the expression of anger in a socially assertive manner can be seen as health
      promoting. The MAQ scales were better predictors of total serum cholesterol
      concentrations than the health related behaviors and characteristics. Results are
      discussed in terms of a psychophysiological risk model of inadequate anger
      coping.

PMID- 8562676
TI  - International Society for the Advancement of Respiratory Psychophysiology
      (ISARP). Inaugural meeting and 13th International Symposium on Respiratory
      Psychophysiology. Saint Flour, France, 25-28 September 1994. Abstracts.

PMID- 8562677
TI  - Differential regulation of progesterone and estradiol production by mouse cumulus
      and mural granulosa cells by A factor(s) secreted by the oocyte.
AB  - Mouse oocytes secrete a factor(s) that inhibits progesterone and enhances
      estradiol production by cumulus granulosa cells. The purpose of this study was to
      investigate the mechanisms by which the production of these steroids is
      modulated. Mouse oocyte-cumulus cell complexes (intact) and complexes from which
      the oocytes were removed microsurgically (oocytectomized; OOX) were cultured for
      up to 48 h in the presence of FSH (150 ng/ml) and testosterone (5 x 10(-7) M).
      For these experiments, all cells were obtained from antral follicles of 24- to 26
      day-old mice primed with eCG. Intact complexes produced primarily estradiol, with
      significant accumulation occurring between 24 and 48 h. In contrast, OOX
      complexes produced little estradiol but, starting at 18 h of culture, released
      significantly more progesterone than did intact complexes. Progesterone
      accumulation in cocultures of denuded oocytes with either OOX complexes or
      monolayers of mural granulosa cells was significantly reduced compared to that
      with OOX complexes or mural granulosa cells cultured alone. If dibutyryl cAMP
      replaced FSH in the cocultures, similar results were obtained, suggesting that
      the oocyte-secreted steroid-regulating factor acts downstream of the generation
      of cAMP to inhibit progesterone production. Since estradiol can inhibit
      progesterone production by granulosa cells, we investigated the possibility that
      the increased progesterone released by OOX complexes was secondary to the lower
      estradiol production. Intact complexes cultured in the presence of the
      nonaromatizable androgen, 5 alpha-dihydrotestosterone, or steroidal (4
      hydroxyandrostenedione) or non-steroidal (CGS 16949A) aromatase inhibitors
      produced little estradiol; however, progesterone production by these complexes
      was no different from that of estradiol-producing intact complexes. These results
      suggest that the steroid-regulating factor(s) secreted by occytes acts to
      regulate granulosa cell production of estradiol and progesterone by independent
      mechanisms.

PMID- 8562678
TI  - Patterns of melatonin secretion during sexual maturation in female ferrets.
AB  - These studies were an examination of the changes in function of the pineal gland
      and its secretory product, melatonin, during sexual maturation induced by
      stimulatory photoperiod in ferrets. Plasma melatonin patterns were determined for
      48-h intervals in ferrets undergoing photoperiod-stimulated sexual maturation.
      Sampling regimens were conducted when ferrets were 10, 15, 16, and 23 wk of age.
      Clear daily rhythms in melatonin concentrations were apparent in ferrets as young
      as 10 wk of age. Melatonin secretion increased with the onset of darkness each
      day and fell with lights-on the next morning. When the photoperiod was changed
      from a short day (8L:16D) to a long day (16L:8D) at 15 wk of age, the melatonin
      rise did not contract immediately to the shorter dark phase for at least the
      first two nights. By 1 wk after imposition of the new, long-day photoperiod,
      however, the pattern of melatonin concentrations in plasma was synchronized to
      the new photoperiod. These studies show that ferrets can detect photoperiod at a
      much younger age than that at which they can respond to long days with
      accelerated maturation and further, that while the pineal gland mediates the
      photoperiod-induced maturation of ferrets, other factors are involved in the 5-6
      wk interval between the onset of long days and the maturational response of the
      hypothalamo-hypophyseal-gonadal axis in this species.

PMID- 8562679
TI  - Rooster testicular germ cells and epididymal sperm contain P450 aromatase.
AB  - We recently found that cytochrome P450 aromatase (P450arom) is present in germ
      cells of the mammalian testis and is capable of converting androgens to estrogens
      in the male reproductive tract. The objective of the present study was to
      determine whether testicular germ cells and epididymal sperm of an avian species
      are also capable of synthesizing estrogen. P450arom was localized in the rooster
      testis and epididymal region by immunocytochemistry, using an antiserum generated
      against purified human placental cytochrome P450arom. Immunostaining was present
      in pachytene spermatocytes, round spermatids, elongated spermatids, flagella of
      late spermatids, and sperm in the epididymal region. A positive reaction was also
      found in nonciliated cells of the epididymal region. However, the absence of mRNA
      for P450arom in the epididymal region indicated that the immunoreactive protein
      present in the epididymal region is not synthesized in this region. The
      immunoreactive P450arom found in epididymal sperm was shown to be active through
      use of a 3H2O assay. On the basis of these data, we conclude that rooster
      testicular germ cells and epididymal sperm are sites for the synthesis of
      estrogen, a potential regulator or modulator of germinal epithelium in the testis
      and the epithelium of the epididymal region of the avian species.

PMID- 8562680
TI  - Cyclic change in 3 alpha-hydroxysteroid dehydrogenase in rat ovary during the
      estrous cycle.
AB  - 3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) activity and content in the
      rat ovary were measured at various stages of the estrous cycle, and the enzyme
      protein in the ovary was localized by immunohistochemistry. The cyclic change of
      ovarian 3 alpha-HSD activity towards 5 alpha-dihydrotestosterone (5 alpha-DHT) as
      a substrate was characterized by two peaks. The first peak occurred at 0800 h on
      proestrus; then the reductase activity decreased and reached its minimum at 2000
      h on proestrus. Thereafter, it gradually increased, reaching the second peak
      (170% of the value at 2000 h on proestrus) at noon of estrus. Quantitative
      analysis by immunoblotting revealed that the alteration in 3 alpha-HSD content in
      the rat ovary during the estrous cycle was essentially similar to that in 5 alpha
      DHT reductase activity. Changes in the reductase activities towards 5 alpha
      androstane-3,17-dione and 5 alpha-DHT and in the dehydrogenase activity towards
      androsterone in the ovary were entirely different from those in the 5 alpha-DHT
      reductase activity and 3 alpha-HSD content; on the other hand, the change in
      carbonyl reductase activity towards p-nitroacetophenone was similar to changes in
      5 alpha-DHT reductase activity and 3 alpha-HSD content. Therefore, p
      nitroacetophenone may be a useful substrate, instead of 5 alpha-DHT, for
      detection of 3 alpha-HSD activity at a high sensitivity, since the p
      nitroacetophenone reductase activity was 10-fold higher than the 5 alpha-DHT
      reductase activity. The enzyme was primarily localized in the granulosa cells and
      CL cells. At 2000 h on proestrus, however, the overall intensity of
      immunostaining in the granulosa cells of the Graafian follicles was markedly
      diminished. In addition, immunoreactivity in the CL cells at 0800 h on estrus was
      observed only in the cells outlining the CL in some cases.

PMID- 8562681
TI  - Steroidogenic activity, insulin-like growth factor-I production, and
      proliferation of granulosa and theca cells obtained from dominant preovulatory
      and nonovulatory follicles during the bovine estrous cycle: effects of low
      density and high-density lipoproteins.
AB  - The role of high- and low-density lipoproteins (HDL and LDL) in regulating
      steroidogenic activity, cellular viability and proliferation, and insulin-like
      growth factor-I (IGF-I) production was examined in granulosa and theca cells from
      dominant preovulatory (DO) and nonovulatory (DNO) bovine follicles. Follicles
      were obtained from pluriparous nonlactating beef cows at ovariectomy 24 h after
      administration of a luteolytic dose of prostaglandin F2 alpha (DO) or during the
      first follicular wave on Days 5-8 of the estrous cycle (DNO). Lipoprotein effects
      on hormone production (ng/1.5 x 10(5) viable cells) and cell viability were
      studied in serum-free, defined medium containing LH and FSH (granulosa) or LH
      only (theca). During late stages (96-144 h) of culture, HDL in the presence of
      gonadotropins increased (p < 0.001) the production of progesterone by granulosa
      and theca cells and the production of IGF-I by granulosa cells. LDL did not
      stimulate granulosa or thecal progesterone synthesis and attenuated HDL
      stimulated progesterone production by both cell types. Gonadotropin stimulation
      of terminal synthetic pathways was either attenuated (granulosa estradiol
      production) by addition of lipoproteins or maximally stimulated (theca cell
      androstenedione production) by a combination of LDL and HDL. Both lipoproteins
      increased (p < 0.05) granulosa cell viability in both follicle types, and a
      marked proliferation (p < 0.001) of steroidogenically inactive theca cells was
      observed from DO but not DNO follicles. Proliferation potential appeared to be
      switched off during the late stages of maturation of DNO follicles and switched
      on after induced luteal regression and rescue of DO follicles.

PMID- 8562682
TI  - Sperm motility hyperactivation facilitates penetration of the hamster zona
      pellucida.
AB  - These experiments were conducted to determine whether or not sperm motility
      hyperactivation facilities penetration of the zona pellucida of the oocyte. Two
      approaches were used. For the first, hamster sperm were incubated for 4.0-4.25 h
      in a capacitating medium that contained either 2.9 or 25.0 mM sodium bicarbonate.
      In these media, sperm became equally capacitated as evidenced by their ability to
      undergo the acrosome reaction when exposed to lysophosphatidyl choline or intact
      zonae pellucidae; however, sperm became hyperactivated only in the medium
      containing 25.0 mM bicarbonate. When these sperm were added to cumulus-free
      oocytes in vitro, only 2 of 88 oocytes were penetrated by sperm preincubated in
      2.9 mM bicarbonate, while 31 of 86 oocytes were penetrated by sperm in 25.0 mM
      bicarbonate. It was found that equal numbers of sperm were bound to the oocytes
      and that equal numbers were acrosome-reacted on the surface of the zonae in the
      two media. For the second approach, sperm were incubated in a capacitating medium
      containing 25 mM bicarbonate. When > 70% were hyperactivated, aliquots were added
      to three sets of oocytes. After 10 min had been allowed for sperm to attach and
      acrosome-react, inhibitors of hyperactivation were added and the sperm and
      oocytes were incubated for an additional 20 min before fixation and examination
      for zona penetration. In the dishes treated with the inhibitors verapamil or
      Cd2+, 1 of 42 and 0 of 42 oocytes were penetrated, respectively, compared with 25
      of 40 in controls. Therefore, it appears that hyperactivation facilitates
      penetration of the hamster zona pellucida.

PMID- 8562684
TI  - Placental metabolism of cortisol at mid- and late gestation in swine.
AB  - An experiment was conducted in pigs to determine the source of fetal cortisol at
      50 (n = 5) or 100 days (n = 4) of gestation (term = 114 days). Equilibrium
      concentrations of tritiated cortisol were achieved, and all hormonal measures
      were made at 110, 130, 140, and 150 min in anesthetized pigs. Maternal plasma
      cortisol did not differ (p = 0.48) between 50 (70.2 +/- 7.4 ng/ml; mean +/- SEM)
      and 100 days (62.4 +/- 5.8 ng/ml). Conversely, fetal cortisol increased (p =
      0.048) between 50 (8.5 +/- 2.5 ng/ml) and 100 days (24.2 +/- 4.2 ng/ml), and, at
      each gestational age, values were lower (p = 0.001) than those in maternal
      plasma. Plasma cortisone (15.1 +/- 2.3 ng/ml) did not change with gestational age
      (p = 0.42) in either compartment (maternal or fetal), nor did it differ between
      compartments (p = 0.08). Maternal cortisol accounted for 22.8 +/- 2.0% of fetal
      cortisol at 50 days of gestation, and this contribution decreased (p < 0.001) to
      5.87 +/- 0.8% at 100 days. At both ages, maternal cortisol accounted for almost
      50% of fetal cortisone. Metabolism of maternal cortisol by the entire
      uterofetoplacental unit was 8.4 +/- 1.7% at 50 days and 7.5 +/- 2.4% at 100 days
      (p = 0.76). The maternal metabolic clearance rate of cortisol increased 44% (p =
      0.003) between 50 and 100 days (1.49 +/- 0.4 vs. 2.15 +/- 0.2 L/min). Hence at
      these gestational ages, the fetus--presumably the fetal adrenal--is the primary
      source of fetal plasma cortisol. The major contribution of maternal cortisol to
      fetal cortisone strongly suggests the presence of porcine placental 11 beta
      hydroxysteroid dehydrogenase activity. Further, factors constituting the
      placental "barrier" that metabolize maternal cortisol to cortisone and other
      products may be major regulators of porcine fetal plasma cortisol and cortisone.

PMID- 8562683
TI  - Relaxin-induced deoxyribonucleic acid synthesis in porcine granulosa cells is
      mediated by insulin-like growth factor-I.
AB  - Relaxin stimulates in vitro DNA synthesis and cell proliferation of porcine
      granulosa cells (GC) and theca cells. The objective of the study reported here
      was to determine whether components of the ovarian insulin-like growth factor
      (IGF) system mediate relaxin's growth-promoting effects on porcine GC in vitro.
      In small follicle GC, relaxin (1-100 ng/ml) significantly (p < 0.05) increased
      IGF-I secretion to 25-34% above control. Hormonal responsiveness of GC was shown
      by incubation with FSH (200 ng/ml), which resulted in 125% stimulation of IGF-I
      secretion relative to that in cells incubated alone. When IGF-I activity in the
      GC cultures was neutralized with a specific IGF-I antibody, relaxin (10 and 100
      ng/ml)-induced [3H]thymidine incorporation was inhibited (p < 0.05). Coincubation
      with IGF-I antibody also suppressed basal and IGF-I (10 ng/ml)-induced
      [3H]thymidine incorporation into GC DNA, but had no effect on insulin (1
      microgram/ml)-induced DNA synthesis, demonstrating the specificity and lack of
      toxicity of the IGF-I antibody. Ligand blot analysis showed no change in
      secretion of GC IGF binding protein (IGFBP) in response to relaxin (1, 10, and
      100 ng/ml). In contrast, IGF-I (10 ng/ml) increased secretion of IGFBP-3 and -5,
      whereas FSH (200 ng/ml) decreased IGFBP-3 secretion and increased IGFBP-4
      secretion (p < 0.05). In IGF-I receptor competition studies, IGF-I, but not
      relaxin, displaced [125I]IGF-I from the GC IGF-I receptor. These studies provide
      direct evidence for an interaction of relaxin and the ovarian IGF system. They
      are the first to show 1) a stimulatory effect of relaxin on IGF-I secretion; 2)
      the necessity of IGF-I activity for relaxin-induced GC DNA synthesis; and 3) the
      absence of an effect of relaxin on GC IGFBPs or IGF-I receptor. These findings
      support a paracrine role for relaxin in the porcine follicle and show that
      relaxin acts indirectly to promote follicle growth by stimulating GC IGF-I
      secretion.

PMID- 8562685
TI  - Regulation of rat granulosa cell plasminogen activator system: influence of
      interleukin-1 beta and ovarian follicular development.
AB  - Tissue remodeling that accompanies ovarian follicular cell proliferation and
      migration during follicular maturation and ovulation involves enzymatic
      degradation of extracellular matrix by proteases such as plasminogen activator
      (PA). However, the potential role of interleukin-1 beta (IL-1 beta) in the
      regulation of the rat granulosa cell PA system during folliculogenesis is not
      known. In vitro treatment of both undifferentiated and differentiated granulosa
      cells with FSH (400 ng/ml) elicited a significant increase in secreted (PAs) and
      cell-associated (PAc) PA activities, which were inhibited by IL-1 beta (0.5-50
      ng/ml) in a concentration- and time-dependent manner. Basal PAs and PAc
      activities were stimulated in cultures of undifferentiated granulosa cells by IL
      1 beta but attenuated in differentiated ones. The inhibitory effect of IL-1 beta
      was accompanied by an increase in PA inhibitor (PAI) activity irrespective of the
      stage of follicular development. Both urokinase-type PA (uPA; 30 kDa) and tissue
      type PA (tPA; 55 KDa) activities were present in cultures of undifferentiated
      granulosa cells, but only tPA was detectable in differentiated granulosa cell
      cultures. Activity of both enzymes was stimulated by FSH but inhibited by the
      cytokine in vitro. Whereas FSH-induced differentiation of granulosa cells as
      indicated by an increase in progesterone (P) secretion was attenuated by IL-1
      beta irrespective of the cytodifferentiative state of granulosa cells, the
      inhibitory effect of gonadotropin on DNA synthesis was reversed by the cytokine
      at both stages of follicular maturation. These findings suggest that during
      ovarian folliculogenesis, IL-1 beta may modulate the progression of granulosa
      cells from a proliferative to a differentiated state and may play a control role
      in determining the fate of the follicle (i.e., ovulation vs. atresia).

PMID- 8562686
TI  - Size variations in the mucin-type domain of hamster oviductin: identification of
      the polypeptide precursors and characterization of their biosynthetic maturation.
AB  - The recent sequencing of a cDNA clone for hamster oviductin revealed that this
      zona pellucida-associated glycoprotein is a particularly intriguing chimeric
      molecule because it encloses regions of significant similarity with chitinase
      related proteins as well as a carboxyterminal mucin-type domain. This domain
      contains contiguous Ser/Thr-rich repeated stretches of 15 amino acids; similar
      units are also found in the deduced sequence of human oviductin. Such structural
      domains constitute a central feature of mucins. We amplified this region from 16
      hamster oviductin cDNA clones and identified three length variants. In order to
      elucidate the biosynthetic maturation of the glycoprotein, a high-titer antiserum
      against synthetic peptides derived from internal sequences of hamster oviductin
      was produced and used in pulse-chase experiments. Two major and one minor
      polypeptide precursors were identified from tunicamycin-treated cell lysates and
      in vitro translated products from oviductal poly(A)+ RNA. Their apparent
      molecular masses correlate with the predicted lengths of the three size variants
      identified by polymerase chain reaction (PCR) amplification. Using glycosylation
      and transport inhibitors, we sought to dissect the posttranslational sequential
      steps leading to the final maturation of hamster oviductin and proposed a
      compartmental model for its biosynthesis. The polypeptide precursors are rapidly
      converted in the endoplasmic reticulum into an N- and O-glycosylated premature
      form of 80-90 kDa (time < 20 min), which is further O-glycosylated and sulfated
      in the trans-Golgi network, giving rise to the secreted species of 160-350 kDa.
      The polymorphism in the heavily O-glycosylated region of hamster oviductin is
      predicted to increase the heterogeneity of the glycoprotein. Such changes may
      alter the putative biological function of the different variants mediated by
      their mucin-type domain, such as protection of the embryo and/or adhesion-related
      phenomena.

PMID- 8562687
TI  - Isolation of a bovine uterotropic placental factor and development of an enzyme
      immunoassay in peripheral serum.
AB  - Bovine uterotropic placental factor (bUTPF) was obtained from bovine term
      placentae that had been homogenized and extracted in acidic medium. The extracts
      were chromatographed on Sephadex G-75, a fraction named native bUTPF was
      obtained, and an antiserum was generated. The native bUTPF was chromatographed on
      Sephacryl S-300 HR, and a 230-kDa fraction was obtained. A competitive enzyme
      immunoassay (EIA) was developed to determine bUTPF levels during gestation. This
      EIA was linear between 0 and 80 micrograms/ml (with a detection limit of 0.2
      microgram/ml) and showed intraassay and interassay coefficients of variation of
      11.2% and 15.5%, respectively. Bovine UTPF serum levels during gestation were
      determined by means of a cross-sectional study between the first month of
      gestation and delivery. Maximal serum levels of bUTPF were found during the first
      month of gestation: 7.1 +/- 1.9 micrograms/ml (p < 0.05). In another cross
      sectional study, blood samples were collected from 105 cows between 8 and 25 days
      postinsemination (day of insemination = Day 0). Levels of bUTPF were found to be
      significantly higher (p < 0.05) by Day 17 compared to Day 0 (5.8 +/- 2.2
      micrograms/ml vs. 1.2 +/- 0.7 micrograms/ml). We conclude that bUTPF is detected
      by EIA in maternal peripheral serum early during gestation in the bovine species.

PMID- 8562688
TI  - Multiple transcripts encoding heme oxygenase-2 in rat testis: developmental and
      cell-specific regulation of transcripts and protein.
AB  - We report for the first time that heme oxygenase-2 (HO-2) expression is regulated
      by developmental and cell type-specific factors in the testis, and we describe
      the presence of three unique sizes of HO-2 transcripts in the testis. HO-2,
      together with HO-1 (HSP32), catalyzes oxidative cleavage of the heme molecule to
      biliverdin, carbon monoxide, and iron; HO-2 is the major isozyme of the testis.
      Northern blot analysis was used to demonstrate the presence of five transcripts
      for HO-2 in rat testis mRNA; they range from approximately 1.3 to approximately
      2.1 kg in length with a predominant 1.45-kb message; three of the transcripts,
      approximately 1.45 kb, approximately 1.7 kb, and approximately 2.1 kg, are unique
      to testis. The two other transcripts of approximately 1.3 and approximately 1.9
      kb are common to every tissue examined, including the testis. Analysis of three
      distinct cDNAs isolated from rat libraries in phage lambda indicates that all are
      identical from -37, relative to translation initiation through the coding region
      to the first of two poly(A) signals previously identified in the HO-2 gene
      (McCoubrey and Maines, 1994). Upstream of -37, the 5' untranslated sequences of
      the isolates differ in both length and sequence. Comparison with the genomic
      sequence suggests that the multiple transcripts arise by splicing of alternative
      first exons as well as use of alternate poly(A) signals. Northern hybridization
      with probes specific for the unique portion of each cDNA are consistent with this
      interpretation. Further, unlike HO-1, HO-2 messages are developmentally
      regulated; only approximately 1.3- and approximately 1.9-kb transcripts were
      detected, at minute levels, in the testis RNA of 7-day-old rats. A pronounced
      increase in total message level was observed by Day 28 postpartum, although the
      level had not reached the marked amplification seen in the adult testis. Further,
      the transcript patterns differed when Day 28 and adult testis were compared to
      Day 7 testis. The very predominant approximately 1.45-kb band and the
      approximately 1.7- and 2.1-kb bands were absent from Day 7 testis. Heme oxygenase
      activity and HO-2 protein levels, as assessed by Western blot, reflect the
      increases at the RNA level. Interestingly, although abundant HO-2 mRNA can be
      detected by in situ hybridization in spermatogonia, spermatocytes, and
      spermatids, HO-2 protein was detected, by immunocytochemistry, only in
      spermatids. These observations demonstrate tissue and cell specificity of HO-2
      gene expression and suggest that in the testis, HO-2 expression is regulated at
      the transcriptional and translational levels.

PMID- 8562689
TI  - Presence and localization of tumor necrosis factor alpha in the corpus luteum of
      nonpregnant and pregnant pigs.
AB  - The objectives of this study were to determine whether tumor necrosis factor
      alpha (TNF alpha) is present in porcine corpus luteum (CL) and, if so, to
      ascertain which cells of the CL were associated with TNF alpha. The influence of
      the reproductive state of the animals on the amount or cellular localization of
      TNF alpha in the CL was also investigated. Western blot analysis demonstrated the
      presence of a 34-kDa immunoreactive TNF alpha-like protein in CL from nonpregnant
      and pregnant pigs. The intensity of TNF alpha immunostaining in bands observed in
      Western blots did not differ when luteal protein from nonpregnant pigs or from
      pregnant pigs was analyzed. Positive immunostaining for TNF alpha, determined by
      immunocytochemistry, was localized within endothelial cells of luteal sections.
      Positive immunocytochemical staining was recorded in all reproductive states
      examined except in CL that had undergone functional luteolysis (reduced
      progesterone concentration). A single-cell assay for TNF alpha secretion (a
      reverse hemolytic plaque assay) confirmed in vitro secretion of TNF alpha by a
      cell type in luteal tissue with a size and nuclear morphology similar to an
      endothelial cell. The presence of TNF alpha in the endothelial cells in
      functional CL is consistent with a role for TNF alpha in the regulation of
      vascular development of the CL in swine.

PMID- 8562690
TI  - Evidence for germ cell control of Sertoli cell function in three models of germ
      cell depletion in adult rat.
AB  - In order to clarify the role of germ cells in the regulation of Sertoli cell
      secretions, three experimental models of germ cell depletion were used:
      hypodactyl rat mutation (testis weight [TW]: 55% less than controls), in utero
      busulfan treatment (TW: 88% less than controls), and neonatal experimental
      cryptorchidism (TW: 72% less than controls). The aim of this work was to compare
      the numbers of Leydig and Sertoli cells and the production of germ cells in each
      experimental model to the in vitro secretions of Leydig and Sertoli cells in
      conditioned media and to the hormonal serum profiles of the same animal in vivo.
      In the three models, serum levels of hypophyseal and testosterone hormones were
      significantly increased and decreased, respectively. In the absence of germ
      cells, the total length of seminiferous tubules, the total numbers of Sertoli and
      Leydig cells, and the daily production of germ cells were significantly
      diminished. The addition of both control and damaged seminiferous tubule culture
      media (STM: media conditioned by 10 cm of seminiferous tubules) to 10(6) control
      or damaged Leydig cells led to a further increase of testosterone production
      after ovine LH stimulation. However, expressed per Sertoli cell, testosterone
      production by control Leydig cells was reduced by addition of damaged STM as
      compared to addition of control STM, and similarly, the addition of control STM
      to damaged Leydig cells enhanced testosterone production more than did the
      addition of damaged STM. Secretions of transferrin per Sertoli cell in STM were
      reduced as compared to controls by the absence of germ cells but to a lesser
      extent than was production of spermatocytes and of spermatids. In conclusion,
      secretions by Sertoli cells of the paracrine factor involved in the control of
      testosterone production by Leydig cells and of transferrin are modified by germ
      cells.

PMID- 8562691
TI  - Human recombinant follistatin-288 suppresses plasma concentrations of follicle
      stimulating hormone but is not a significant regulator of luteinizing hormone in
      castrated rams.
AB  - We have tested the hypothesis that treatment of castrated rams (wethers) with
      human recombinant follistatin-288 (FS-288) suppresses plasma concentrations of
      FSH but has no effect on plasma concentrations of LH. Wethers were given an i.v.
      injection of vehicle or 50 micrograms FS-288 followed by a 12-h i.v. infusion of
      vehicle or 800 micrograms FS-288, respectively. This dose and treatment regimen
      was identical to that used in a previous study in which wethers were treated with
      vehicle or human recombinant inhibin A (hr-inhibin). Human recombinant
      follistatin significantly (p < 0.05) suppressed plasma concentrations of FSH, but
      vehicle had no effect. The maximal suppression of FSH occurred 12-15 h after the
      start of treatment, at which time the plasma concentrations were reduced by
      20.6%. The reduction in plasma concentrations of FSH caused by FS-288 was about
      2.6-fold less than that observed after the same treatment with hr-inhibin. FS-288
      had no effect on plasma concentrations of LH; this result was similar to the
      findings we obtained with hr-inhibin. These data suggest that follistatin is a
      less potent negative regulator of FSH secretion than inhibin and that follistatin
      is not a significant regulator of the secretion of LH in rams.

PMID- 8562692
TI  - Influence of stage of the estrous cycle on insulin-like growth factor-I
      modulation of luteinizing hormone secretion in the gilt.
AB  - Follicular phase (FOL; Days 17-19; n = 8), luteal phase (LUT; Days 7-9; n = 6),
      and ovariectomized (OVX; n = 5) crossbred gilts were used (Day 0 = onset of
      estrus). Blood samples were collected via jugular vein cannula every 15 min for 2
      h the day before pituitary collection. Serum was assayed for insulin-like growth
      factor (IGF)-I, IGF-I binding proteins (IGFBP), LH, estradiol (E2), and
      progesterone (P4). Anterior pituitary cells were dispersed, cultured, and
      challenged on Day 4 of culture (Day 0 = day of seeding) with 10(-7) M GnRH or IGF
      I (10(-11), 10(-10), 10(-9), 10(-8), or 3 x 10(-8) M) individually or in
      combination. Serum E2 and P4 concentrations indicated that the animals were in
      the appropriate stage of the estrous cycle. Mean serum LH concentrations were
      greater (p < 0.0004) for OVX animals compared to FOL and LUT animals. Mean serum
      IGF-I concentrations were lower (p < 0.05) for OVX compared to FOL and LUT
      animals, while serum IGFBP were not different among animals. Basal LH secretion
      (control) was greater (p < 0.04) in OVX than in FOL or LUT cultures. Relative to
      control, 10(-11) M IGF-I increased (p < 0.02) LH secretion in FOL, LUT, and OVX
      cultures, and this response was greater (p < 0.05) in FOL and OVX than in LUT
      cultures. Only the 10(-11) M IGF-I enhanced basal LH secretion in LUT cultures.
      In addition, 10(-10) M IGF-I increased (p < 0.05) LH secretion in OVX cultures,
      and 10(-10) and 10(-9) M IGF-I stimulated (p < 0.05) LH secretion in FOL
      cultures, whereas basal LH secretion in all groups was unaffected (p > 0.05) by
      10(-8) or 3 x 10(-8) M IGF-I. The GnRH-induced LH secretion was unaltered by IGF
      I treatment. Results indicate that in vitro IGF-I treatment increased basal LH
      secretion, with reproductive status modulating LH response to IGF-I.

PMID- 8562693
TI  - Restoration of normal adult penile erectile response in aged rats by long-term
      treatment with androgens.
AB  - In order to determine whether the aging-related impairment of penile erection can
      be corrected by exogenous androgens, 20-mo-old ("old") rats received implants of
      Silastic tubing containing either testosterone (T) or dihydrotestosterone (DHT).
      Untreated aged-matched rats were used as reference controls, and values were
      compared with those obtained previously for 5-mo old ("adult") rats. After 45
      days, groups of six rats were submitted to electrical field stimulation of the
      cavernosal nerve (EFS), and the intracavernosal pressure and mean arterial
      pressure (MAP) were recorded. Compared to the untreated old rats, the old animals
      receiving either T or DHT showed a similar and significant (p < 0.01) increase
      (56%) in the maximal intracavernosal pressure (MIP) to a level slightly above
      that of the untreated adult rats. The response was sensitive to the nitric oxide
      synthase (NOS) inhibitor Nw-nitro-L-arginine methyl ester (L-NAME). The MIP:MAP
      ratio in the treated animals was nearly double that found in the old untreated
      controls. Penile NOS activity was measured by the [3H]L-arginine-citrulline
      conversion, and neuronal NOS (nNOS) levels were estimated by a semiquantitative
      Western blot assay with antibodies against human nNOS. No significant variations
      were observed in either NOS levels or NOS activity between the treated and
      untreated old rats. These results suggest that aging-related erectile dysfunction
      in the intact rat may be responsive to androgen therapy and that this correction
      is not associated with an increase in the basal levels of penile NOS, in contrast
      to what occurs in castrated rats.

PMID- 8562694
TI  - Is corpus luteum regression an immune-mediated event? Localization of immune
      system components and luteinizing hormone receptor in human corpora lutea.
AB  - Factors determining the life span of the human corpus luteum (CL) are not known.
      In addition to being determined by hormonal factors, such as hCG, the life of
      luteal cells may be determined by the preservation of luteal vascularization.
      Furthermore, the CL represents an immunologically unique tissue, as it is formed
      after menarche, long after adaptation of the immune system toward self. Thus, CL
      regression may be immunologically mediated. To determine what role the
      vasculature and immune system play in human CL development and regression, we
      examined immunohistochemically 1) the expression of Thy-1 differentiation protein
      by vascular pericytes, 2) the expression of major histocompatibility complex
      (MHC) class I and class II molecules in granulosa lutein cells (GLC), and 3)
      infiltration of the CL by macrophages and T lymphocytes. LH receptor (LHR) and
      cytokeratin 18 expression were also studied. In developing CL, the pericytes of
      luteal microvasculature released Thy-1 differentiation protein among the
      endothelial cells of proliferating vessels. In mature CL, Thy-1 released from
      vascular pericytes accumulated on the surface of GLC, and these cells exhibited
      LHR immunoreactivity (LHRI). Overall LHRI increased during the luteal phase and
      was strongest at the beginning of the late luteal phase. Although vascular
      pericytes showed strong LHRI, no staining of endothelium was detected during the
      luteal phase. GLC exhibited strong cytokeratin staining and moderate staining for
      MHC class I and MHC class II antigens; numerous macrophages were detected in
      luteal tissue. During pregnancy, the staining pattern was similar to that seen in
      the mature CL at the end of the midluteal phase. During the late luteal phase,
      surface expression of MHC class I and MHC class II antigens by GLC was
      substantially enhanced, and some T cells invaded among luteal cells. By the end
      of the cycle, an acute regression of vasculature and luteal tissue was observed
      along the fibrous septa. The remaining GLC showed only surface and no cytoplasmic
      LHRI. During the subsequent cycle, in the presence of numerous T cells,
      regressing GLC exhibited strong surface expression of various macrophage markers,
      such as CD4, CD14, CD68, and leukocyte common antigen, a feature not detected in
      the CL during the luteal phase nor described in other tissues. A complete loss of
      cytokeratin staining in GLC was observed. In regressing CL, strong LHRI was
      present in the endothelium of small and large luteal vessels. In conclusion,
      vascular pericytes and macrophages may stimulate the development and senescence
      of luteal tissue. The senescence of GLC may be inconsistent with preservation of
      luteal vasculature, and T lymphocytes appear to participate in terminal
      regression of the CL. Regression of luteal tissue therefore resembles immunologic
      rejection of a transplant. During pregnancy, the aging process of GLC appears to
      be interrupted, possibly due to the temporary acceptance of the CL "graft."

PMID- 8562695
TI  - Lamb birth weight is affected by culture system utilized during in vitro pre
      elongation development of ovine embryos.
AB  - It has previously been reported that ovine embryos cultured in Synthetic Oviduct
      Fluid medium supplemented with 20% human serum (SOF+HS) develop into lambs with a
      high birth weight. We have investigated this phenomenon by culturing ovine
      zygotes in SOF+HS or a serum-free version of Synthetic Oviduct Fluid with BSA and
      amino acids (SOFaaBSA) in place of serum. Zygotes were either obtained from
      superovulated and naturally mated ewes or produced in vitro. Embryos were
      subsequently transferred to synchronized recipient ewes (n = 63). An additional
      group of ewes (n = 16) served as flock fertility and lambing controls.
      Development of zygotes to stages suitable for transfer (i.e., good to excellent
      compact morulae or blastocysts) was not affected by medium (SOFaaBSA = 53 +/- 5%
      vs. SOF+HS = 59 +/- 5%) but was affected by source (in vivo-derived = 74 +/- 5%
      vs. in vitro-derived = 35 +/- 5%, p < 0.001). Embryos incubated in SOF+HS were
      morphologically different from those incubated in SOFaaBSA, having abundant lipid
      droplets. Pregnancy rate (65%) and embryo survival (48%) of recipients determined
      by ultrasonography on approximately Day 60 of pregnancy did not differ between
      medium treatments or source of embryo. Mean weight of lambs from embryos cultured
      in SOF+HS (4.2 +/- 0.2 kg) was significantly heavier than that of controls (3.4
      +/- 0.2 kg, p < 0.01) or of lambs from embryos cultured in SOFaaBSA (3.5 +/- 0.2
      kg, p < 0.05). Furthermore, mean gestation length was longer in recipients
      receiving embryos incubated in SOF+HS (147 +/- 1 days) than in SOFaaBSA (145 +/-
      1 day, p < 0.05). Reasons for this birth weight and gestation length difference
      are unclear, but our data suggest that different culture conditions can produce
      embryos with differing morphology, apparent chemical composition, and rate of
      development, resulting in lambs with differing gestation length and birth weight.

PMID- 8562696
TI  - Retinol in addition to retinoic acid is required for successful gestation in
      vitamin A-deficient rats.
AB  - Vitamin A-deficient, pregnant rats resorb their fetuses around Day 15 of
      gestation even when given retinoic acid (RA) daily. This resorption is prevented
      by the administration of retinol. Retinol was found to be required no later than
      Day 10 of gestation, and up to 500 micrograms of retinol administered on Day 11
      or later was not able to change the course of fetal resorption in these animals.
      Vitamin A-deficient pregnant rats supported on 40 micrograms all-trans-RA daily
      that are given 2 micrograms of retinol on Day 10 and then placed on a retinol
      sufficient diet at 24 h after administration of the retinol dose gave birth to
      normal pups. When a single 2-micrograms dose of retinol was administered on Day
      10 and the vitamin A-deficient, RA-supported animals continued on the deficient
      diet supplemented with RA, the fetal resorption did not occur and the fetuses
      appeared normal when examined on Day 20 of gestation. Experiments using
      radiolabeled retinol tracer indicated that while there was some accumulation of
      radioactivity through Day 14 in the fetus, the administered retinol was mostly
      eliminated from the animal by Day 16. Thus, retinol is clearly required by Day 10
      for normal gestation.

PMID- 8562697
TI  - Cellular pattern of c-fos induction by estradiol in the immature rat uterus.
AB  - Previous biochemical studies have shown that c-fos mRNA expression is rapidly and
      dramatically induced by estrogen in the immature rat uterus. In this work we have
      used in situ hybridization and immunocytochemistry to analyze the cellular
      pattern of proto-oncogene induction following administration of estradiol. The c
      fos transcript and protein levels were low in control animals. Three hours after
      hormone treatment, the luminal and glandular epithelium, stroma, and myometrium
      all showed a clear increase in mRNA levels of the proto-oncogene as judged by in
      situ hybridization; this increase was most pronounced in the epithelial cells.
      Immunocytochemistry also demonstrated Fos expression in all cell layers with a
      higher fraction of cells staining in the epithelial and stromal layers than in
      the myometrium. Estradiol thus increased expression of c-fos in all major cell
      types of the immature uterus, although each tissue layer exhibited a specific
      pattern and degree of fos transcript and protein expression. This proto-oncogene
      is thus a marker for estrogen action in all uterine cell types at this stage of
      development. Since estrogen stimulates proliferation in all cell layers of the
      immature uterus, the cellular pattern of fos expression also correlates with the
      proliferative response to the hormone.

PMID- 8562698
TI  - Cytokine secretion by macrophages in the rat testis.
AB  - The rat testis contains a large population of resident macrophages, the
      physiological roles of which are yet to be established. To investigate the
      functional capacity of these cells, we have analyzed the secretion of the
      cytokines interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF alpha), and
      granulocyte macrophage-colony stimulating factor (GM-CSF) by isolated testicular
      macrophages (TMs) and, for comparison, by isolated rat peritoneal macrophages
      (PMs). Cells were cultured for 48 h in serum-free medium alone or with
      lipopolysaccharide (LPS, 10 micrograms/ml) and/or recombinant interferon-gamma
      (rIFN gamma, 200 U/ml). Specific bioassays were used to measure cytokines in the
      media collected from cultures. Basal production of IL-1, TNF alpha, and IL-6 by
      TMs and PMs were similar, but TMs produced 8-fold greater levels of GM-CSF than
      did PMs. LPS, alone or in combination with IFN gamma, significantly enhanced the
      secretion of all cytokines by PMs (340-840% increase). LPS alone had little
      effect on TM secretion except to reduce GM-CSF levels some 4-fold. The addition
      of LPS and IFN gamma increased IL-1, IL-6, and TNF alpha levels (200-750%
      increase) and reduced GM-CSF levels to 45% of basal levels. Treatment of cultures
      with indomethacin to minimize prostaglandin production enhanced the LPS-induced
      effects in both cell types. Expression of the mRNA for each cytokine in cultures
      of testicular and peritoneal macrophages, as well as in intact testis, was
      confirmed by reverse transcription polymerase chain reaction. These studies
      indicate that macrophages resident within the rat testis have a novel cytokine
      secretion profile and an altered responsiveness to inflammatory activators
      compared with macrophages from the peritoneal cavity. This may be important in
      physiological processes in the testis and may contribute to the dysfunctional
      afferent immune activity thought to underlie the immunologically privileged
      status of the testes.

PMID- 8562699
TI  - Stress-induced genetic expression of a selective corticotropin-releasing factor
      receptor subtype within the rat ovaries: an effect dependent on the ovulatory
      cycle.
AB  - The identification of several sources of corticotropin-releasing factor (CRF)
      outside the brain, including the gonads, has suggested the intriguing possibility
      that CRF of systemic origin can influence gonadal function under both normal and
      stressful conditions. However, the exact sites of action and the type of cells
      targeted by this stress-related neuropeptide in the ovaries remain unknown. The
      present study therefore investigated the effect of acute immobilization stress on
      the distribution of the recently cloned CRF receptor (CRF1, CRF2 alpha, and CRF2
      beta) genes in the ovaries of adult cycling female rats (200-250 g; 14 h light,
      lights-on at 0600 h). Reproductive stages were verified by daily vaginal smears
      taken each morning for a minimum of 3-4 cycles prior to the experiment. Three
      hours after the start of a 90-min immobilization session, rats were deeply
      anesthetized and transcardially perfused with a solution of 4% paraformaldehyde
      on the morning (1100 h) and on the afternoon (1700 h) of proestrus and diestrus
      2. Frozen ovaries were mounted on a microtome, cut into 30-microns slices, and
      then processed for the detection of mRNAs encoding CRF1, CRF2 alpha, or CRF2 beta
      receptors by in situ hybridization histochemistry using 35S-labeled riboprobes.
      Whereas the ovaries displayed barely detectable levels of CRF1 receptor mRNA in
      control and in stressed animals on the morning of proestrus and the day of
      diestrus-2, a positive signal for this transcript was detected in stroma cells
      and in the theca surrounding the ovulatory follicles during the afternoon of
      proestrus. Excluding the cumulus oophorus, which showed a light expression of the
      mRNA encoding the type 1 CRF receptor, granulosa cells were completely devoid of
      transcript in Graafian follicles as well as in CL, regardless of the stage of
      maturation. Interestingly, immobilization stress induced a marked expression of
      CRF1 receptor mRNA in the stroma cells in the afternoon of proestrus, suggesting
      that the ovaries may be sensitive to acute neurogenic challenge during the
      preovulatory stage. On the other hand, CRF2 alpha and CRF2 beta receptor mRNAs
      were undetectable both in control and stressed animals throughout the estrous
      cycle. These results provide clear evidence that the gene encoding the CRF1
      receptor but not the type 2 receptors can be finely induced in selective ovarian
      compartments in both control and stressful conditions during the gonadal life
      cycle. The temporal and anatomic selectivity of the ovarian periovulatory CRF1
      receptor gene expression may suggest a critical biological action of CRF during
      the ovulatory process and suggests that the intraovarian environment may
      influence the stress-induced transcription of a selective CRF receptor subtype
      within the ovary.

PMID- 8562700
TI  - Transforming growth factor alpha gene expression and peptide localization in
      porcine ovarian follicles.
AB  - The present study was undertaken to determine transforming growth factor alpha
      (TGF alpha) gene expression in various components of medium-sized porcine ovarian
      follicles by reverse transcription-polymerase chain reaction, and to localize the
      peptide during folliculogenesis by immunocytochemistry. A strong signal for TGF
      alpha transcript was detected in cumulus and granulosa cells, whereas the signal
      in theca cells was very weak but detectable. No TGF alpha mRNA was detected in
      the oocyte. Immunolocalization studies revealed intense TGF alpha staining in
      cumulus and granulosa cells of all stages of follicular development. TGF alpha
      immunostaining was also observed in the oocytes of primordial and primary
      follicles. In antral follicles, immunostaining was observed only in cumulus and
      mural granulosa cells, whereas theca cells and oocytes exhibited very little or
      no detectable staining. TGF alpha immunostaining was absent in follicles
      undergoing atresia. No TGF alpha immunostaining was observed when the antibody
      was omitted from the procedure, and the staining was substantially reduced when
      the primary antibody was preabsorbed with the same mass of TGF alpha peptide,
      suggesting the specificity of the staining procedure. These results suggest a
      local follicular production of TGF alpha in the porcine ovary and thus a role for
      TGF alpha of follicular origin in the regulation of follicular development in an
      autocrine/paracrine fashion.

PMID- 8562701
TI  - Uteroferrin induces lipid peroxidation in endometrial and conceptus microsomal
      membranes and is inhibited by apotransferrin, retinol binding protein, and the
      uteroferrin-associated proteins.
AB  - Iron-containing proteins catalyze lipid peroxidation when combined with either
      H2O2 or ascorbic acid (ASC). Microsomal membranes were prepared from Day 13
      endometrial and conceptus tissues (5 pigs) and from Day 30 endometrial,
      placental, fetal liver, and fetus minus fetal liver tissues (5 pigs). Microsomal
      membranes were subjected to the following in vitro treatments: 1) no treatment,
      2) 50 microM ASC, 3) 100 microM uteroferrin (UF), 4) 50 microM ASC + 100 microM
      UF, 5) 50 microM ASC + 100 microM UF + 10 microM apotransferrin (transferrin with
      no iron bound; ATF), and 6) 50 microM ASC + 100 microM UF + 10 microM
      holotransferrin (transferrin saturated with iron; HTF). For treatments 7 through
      10, membranes were preincubated (0 degrees C, 3 h) with either 7) no treatment,
      8) 50 microM fetuin, 9) 50 microM holoretinol binding protein (holoRBP: retinol
      binding protein [HoloRBP] with retinol bound), or 10) 50 microM apoRBP (RBP with
      no retinol bound) followed by incubation with 50 microM ASC + 100 microM UF.
      Lipid peroxidation was measured in the samples as thiobarbituric acid reactive
      substances (TBARS). Endogenous TBARS were greater (p < 0.05) in Day 13 conceptus
      than in Day 13 endometrium and were highest (p < 0.05) on Day 30 in fetal liver.
      Combined ASC and UF caused a large increase (p < 0.05) in TBARS in all membranes
      except Day 30 placental membranes. Addition of ATF, but not HTF, decreased TBARS
      production in all membrane preparations. HoloRBP, but not fetuin or apoRBP,
      decreased (p < 0.05) TBARS production in all but Day 30 endometrial membranes. In
      other experiments, when combined with ASC, UF/UF-associated protein complex
      induced less (p < 0.01) lipid peroxidation in fetal liver microsomal membranes
      than did free UF. Catalase and superoxide dismutase had no effect on UF-induced
      lipid peroxidation in fetal liver membranes. These results indicate that 1) UF
      combined with ASC induces lipid peroxidation in Day 13 endometrial and conceptus
      and Day 30 endometrial, fetal liver, and fetus minus liver microsomal membranes,
      and 2) ATF, holoRBP, and the UF-associated proteins, but not catalase or
      superoxide dismutase, inhibit this reaction.

PMID- 8562702
TI  - Immortalization and characterization of a Sertoli cell line from the adult rat.
AB  - To facilitate investigations of the regulation of adult Sertoli cell function, we
      have established a Sertoli cell line from sexually mature Sprague-Dawley rats.
      The cells were immortalized with the temperature-sensitive mutant of the SV40
      virus, tsA255. The tsA255 large T antigen is heat-labile and efficiently promotes
      propagation of cells at 33 degrees C (permissive temperature) but is inactive at
      40 degrees C (nonpermissive temperature). The established clonal Sertoli cell
      line (ASC-17D) proliferates indefinitely at the permissive temperature. However,
      within 48 h at the nonpermissive temperature, cell proliferation ceases. ASC-17D
      cells show positive staining with antibodies to cytokeratin and vimentin,
      consistent with the Sertoli cell origin of these cells. Transferrin and sulfated
      glycoprotein (SGP)-2 mRNAs were nearly undetectable in ASC-17D cells cultured at
      the permissive temperature, but expression of both mRNAs was induced at the
      nonpermissive temperature. In contrast, SGP-1 was expressed equally at both the
      permissive and nonpermissive temperatures. There was no increase in either
      transferrin or SGP-2 with FSH or dibutyryl cAMP (db-cAMP) treatment at the
      permissive temperature or with FSH treatment at the nonpermissive temperature.
      However, the steady-state levels of both of these mRNAs were substantially
      increased in the presence of db-cAMP at the nonpermissive temperature. In
      contrast, SGP-1 mRNA was not affected by either FSH or db-cAMP. These results
      suggest that the ASC-17D cell line is derived from adult Sertoli cells and may be
      useful for the study of adult Sertoli cell function.

PMID- 8562704
TI  - Damage to rat spermatozoal DNA after chronic cyclophosphamide exposure.
AB  - Treatment of male rats with low dosages of cyclophosphamide causes a dramatic
      increase in early embryo death among their progeny without significantly
      affecting the general health of the male. It is hypothesized that
      cyclophosphamide exerts its effects by targeting specific components of
      spermatozoal nuclei. The purpose of the present studies was to investigate the
      effects of chronic cyclophosphamide treatment on spermatozoal DNA. Two approaches
      were pursued. The first was to determine total DNA damage by using the alkaline
      elution method. The second was to study spermatozoal DNA template function by
      using an in vitro DNA synthesis system. Adult male rats were treated with saline
      or cyclophosphamide (6.1 mg/kg/day) daily for 1 or 6 wk. Cauda epididymal
      spermatozoa were collected and subjected to alkaline elution using DNA-DNA dot
      hybridization to quantify the fractionated DNA. One week of treatment with
      cyclophosphamide caused DNA single strand breaks that could be detected only in
      the presence of proteinase K in the lysis solution; no DNA cross-links were
      observed in the animals that received 1-wk drug treatment. In contrast, 6 wk of
      treatment with cyclophosphamide induced a significant increase in both DNA single
      strand breaks and cross-links in spermatozoal nuclei; the cross-links were
      attributable primarily to DNA-DNA linkages. The availability of spermatozoal DNA
      for template function was not affected by 1 wk of treatment with cyclophosphamide
      but was markedly affected after 6 wk of treatment with this drug. It is proposed
      that during chromatin transition processes the male genome may be in an open
      dynamic state with many exposed sites that are vulnerable to alkylating agents.
      Since there is no DNA repair during spermiogenesis, damage to the genome by
      alkylation at this stage may be cumulative, resulting in the production of
      dysfunctional germ cells.

PMID- 8562703
TI  - Sertoli cell-spermatogenic cell interaction: the insulin-like growth factor
      II/cation-independent mannose 6-phosphate receptor mediates changes in
      spermatogenic cell gene expression in mice.
AB  - The insulin-like growth factor (IGF)-II/cation-independent mannose 6-phosphate
      receptor (CI-MPR) is a multifunctional receptor with distinct binding sites for
      IGF-II and mannose 6-phosphate (M6P)-bearing glycoproteins. We used the immediate
      early response gene c-fos to assay early changes in gene expression in
      spermatogenic cells in response to ligands for this receptor that are present in
      the seminiferous epithelium. We confirmed that c-fos behaves as an immediate
      early response gene in spermatogenic cells after stimulation of protein kinase C
      with phorbol ester or after intercellular calcium levels are raised with calcium
      ionophore. After determining that IGF-II mRNA is present in Sertoli cells, we
      treated spermatogenic cells with this growth factor and found that it increased c
      fos mRNA levels in a dose-dependent manner. Similarly, Sertoli cell-conditioned
      medium (SCM) caused a dose-dependent increase in c-fos levels in spermatogenic
      cells isolated from adult mice. This effect was inhibited in the presence of 5 mM
      M6P, demonstrating that this change in c-fos gene expression was mediated by the
      IGF-II/Cl-MPR. In addition, SCM treatment of purified pachytene spermatocytes and
      round spermatids caused a dose-dependent increase in 18S rRNA levels that was
      completely abolished in the presence of M6P. Our results provide direct evidence
      that IGF-II/Cl-MPR ligands secreted by Sertoli cells can modulate gene expression
      in spermatogenic cells and strongly suggest that they are important in the
      regulation of spermatogenesis.

PMID- 8562705
TI  - Interferon alpha-2b modulates beta-galactoside alpha-2,6-sialyltransferase gene
      expression in rat testes.
AB  - Sperm surface glycoproteins are modified during passage through the epididymis, a
      process believed to be important in the production of functionally mature
      spermatozoa. The effect of various cytokines on reproductive events has recently
      been investigated, with conflicting results. In the present investigation, the
      effect of interferon-alpha-2b (IFN alpha 2b) on sialyltransferase (ST) activity
      and beta-galactoside alpha-2,6-sialyltransferase (Gal 2,6-ST) mRNA expression was
      studied in rat testicular tissue. The results revealed the presence of Gal 2,6-ST
      mRNA in rat testicular tissue, similar in molecular size to that found previously
      in rat spleen, lung, ovary, kidney, heart, and brain. In addition, we observed
      that IFN alpha 2b reduced Gal 2,6-ST mRNA and ST activity in rat testes by a
      comparable magnitude. These findings provide insight into an additional mechanism
      by which cytokines may affect the reproductive system.

PMID- 8562706
TI  - Isolation of nine different biologically and immunologically active molecular
      variants of bovine follicular inhibin.
AB  - A combination of immunoaffinity chromatography, SDS-PAGE, and electroelution was
      used to simultaneously isolate 0.36-4.65 mg of nine different molecular forms of
      inhibin (pro alpha C-29 kDa; fully processed 34 kDa; and large inhibin forms 49,
      53, 58, 77, 88, 110, and > 160 kDa) from 0.675 L of bovine follicular fluid
      (bFF). Each inhibin form, except pro alpha C, cross-reacted with inhibin alpha C
      1-26-and beta A 82-114-subunit-directed antibodies during immunoblot analysis.
      Pro alpha C cross-reacted only with alpha-subunit antibodies. The inhibin forms
      consisted of 22-, 29-, 49-, or 58-kDa alpha subunits and 17- or 58-kDa beta
      subunits. During cultures of ovine pituitary cells, a 5-ng/ml dose of each
      inhibin form (except pro alpha C) suppressed basal accumulation of FSH 30% to 50%
      but increased GnRH-induced LH release 40% to 248%. The various inhibin forms
      cross-reacted in parallel fashion with standard curves generated during
      homologous and heterologous RIAs but with markedly different relative
      immunopotencies. In the RIAs, pro alpha cross-reacted 3- to 18-fold more than the
      fully processed inhibin form. The fully processed and the seven different large
      forms of inhibin cross-reacted with different relative immunopotencies in a two
      site dimer-specific ELISA. We concluded that 1) a combination of immunoaffinity
      extraction, SDS-PAGE, and electroelution simultaneously isolated relatively large
      amounts of highly enriched preparations of nine different molecular forms of
      immunologically and biologically active inhibin from bFF; 2) eight different
      dimeric forms of bovine inhibin may regulate both basal FSH and GnRH-induced LH
      secretion by the pituitary gland, and 3) eight or nine different molecular forms
      of inhibin cross-react with different relative immunopotencies in the two-site
      dimer-specific assay or RIAs.

PMID- 8562707
TI  - Developmental changes in seminiferous tubule extracellular matrix components of
      the mouse testis: alpha 3(IV) collagen chain expressed at the initiation of
      spermatogenesis.
AB  - The temporal expression of type IV collagen, laminin, and entactin in the basal
      laminae of the seminiferous tubule during development of the mouse testis was
      determined. Northern blot analysis was used to examine changes in testicular mRNA
      for alpha 1-alpha 5 type IV collagen (IV) chains in mice ranging in age from
      newborn to adult (60 days). Levels for mRNA alpha 1(IV) and alpha 2(IV) chains
      were highest in newborns through Day 5 and remained elevated through Day 10, but
      then sharply declined to adult values by Day 30. In sharp contrast, alpha 3(IV)
      and alpha 4(IV) chain levels were low in newborns, peaked at Day 10, and then
      declined to adult values by Day 30. 5(IV) mRNA was elevated in newborns and at
      Days 5 and 10 before dropping to adult levels by Day 30. Changes in the
      deposition of alpha 1, alpha 2, and alpha 3(IV) collagen chains, laminin, and
      entactin into the inner and outer basal laminae of the seminiferous tubule were
      determined from the beginning of tubule formation (embryonic Day 12.5) through
      adulthood by immunofluorescence microscopy using polyclonal antibodies for these
      constituents. The alpha 1 and alpha 2(IV) chains, laminin, and entactin were
      deposited into the inner basal lamina at embyronic Day 12.5 and into the newly
      formed outer basal lamina at Day 5 after birth. The alpha 3(IV) chains were
      deposited into both the inner and outer basal laminae at Day 5. Thus, testicular
      alpha 1-alpha 3(IV) mRNA levels coincide with the incorporation of detectable
      collagen chains into the seminiferous basal laminae, suggesting transcriptional
      control of these alpha (IV) chains. Expression of of the alpha 3(IV) chain
      coincides with the initiation of spermatogenesis, suggesting a functional role of
      this chain in spermatogonial proliferation.

PMID- 8562708
TI  - Secretion of biologically active interferon tau by in vitro-derived bovine
      trophoblastic tissue.
AB  - Secretion of interferon tau (IFN tau) by trophoblastic tissue has been shown to
      be the first embryonic signal for pregnancy recognition. Therefore we tried to
      derive biologically active trophoblastic tissue by in vitro techniques. Since
      conventional in vitro conditions for bovine embryo development were not
      sufficient for long-term culture, we tested more complex culture conditions,
      including Menezo B2 or Buffalo rat liver (BRL) cell-conditioned medium, for their
      ability to support proliferation and IFN tau secretion by in vitro-derived
      trophoblastic tissue. IFN tau activity was determined by using a biological assay
      based on the inhibition of the cytopathic effect of vesicular stomatitis virus on
      Madin-Darby bovine kidney cells. When cultures of individual hatched blastocysts
      were started in 60-microliters drops of BRL cell-conditioned medium, mean IFN tau
      secretion (antiviral units/ml/48 h) corresponded to 1200 on Day 11 and to 5000 on
      Day 13 (p < 0.01). To characterize trophoblast cell-specific secretions, the
      inner cell mass was removed from all embryos by microsurgery on Day 13. IFN tau
      secretion by trophoblastic tissue increased to mean levels of > 10(5) antiviral
      units/ml/48 h on Day 23m, stayed high for about 1 wk, and then slowly declined to
      levels below 10(3) antiviral U/ml/48 h. The specificity of the cytoprotective
      effect of IFN tau was tested by Western blot analysis and by immunoneutralization
      with use of a polyclonal antiserum specific to IFN tau. Our results demonstrate
      that viable trophoblastic tissue can be maintained entirely in vitro and secretes
      high amounts of IFN tau.

PMID- 8562709
TI  - Regulation of the activin-binding protein follistatin cultured human luteinizing
      granulosa cells: characterization of the effects of follicle stimulating hormone,
      prostaglandin E2, and different growth factors.
AB  - Regulation of the activin-binding protein follistatin (FS) by recombinant human
      (rh) FSH, prostaglandin E2 (PGE2), and several polypeptide growth factors was
      examined in cultures of human granulosa-luteal (GL) cells obtained from in-vitro
      fertilization patients at oocyte retrieval. Northern and dot blot hybridization
      analyses demonstrated that both rhFSH and PGE2 caused stimulatory effects on FS
      mRNA levels in a culture stage-, time-, and concentration-dependent manner. An 8
      h stimulation with rhFSH (100 ng/ml) significantly increased FS mRNA levels on
      Days 5 and 7 of culture and PGE2 (10(-6)M) on Days 2, 4, and 7. The stimulatory
      effect of rhFSH and PGE2 on FS mRNA levels were rapid and transient. Maximal
      inductions occurred 8 h after stimulation, whereas weak or no stimulatory effects
      were seen at 24 or 48 h. PGF2 alpha did not affect FS mRNA levels at any time
      point studied. Treatment of the cells with the protein synthesis inhibitor
      cycloheximide prior to rhFSH stimulation did not inhibit the rapid induction of
      FS mRNAs, but it prevented the decline at 24 h. Both rhFSH and PGE2 clearly also
      increased the levels of secreted FS proteins are detected by immunoprecipitation
      studies with a specific antibody. The effects of the polypeptide growth factors
      epidermal growth factor (EGF); transforming growth factor beta 1 (TGF beta 1),
      and activin A on FS mRNA levels were also examined. TGF beta 1 and activin A had
      no effect on basal FS expression at any concentration or time point studied. An 8
      h stimulation with EGF increased FS mRNA levels, but the effect was weaker than
      those caused by rhFSH and PGE2. We conclude that rhFSH and PGE2 induce FS mRNA
      and protein in human cultured GL cells. EGF is able to induce FS mRNA to a lesser
      extent than are rhFSH and PGE2, whereas PGF2 alpha, TGF beta 1, and activin A do
      not affect basal FS mRNA levels in human cultured GL cells. This study together
      with our previous report on the stimulatory effect of hCG on FS levels suggest
      that in the luteal phase of the human menstrual cycle, FS expression in granulosa
      cells is likely to be positively controlled by luteotropic factors such as
      gonadotropins and PGE2. Consequently, elevated FS levels may support the survival
      of the human CL since FS is known to prevent the antisteroidogenic effects of
      activin in human GL cells.

PMID- 8562710
TI  - An estrogen-dependent sheep oviductal glycoprotein has glycan linkages typical of
      sialomucins and does not contain chitinase activity.
AB  - The deduced amino acid sequence of an estrogen-dependent sheep oviductal
      glycoprotein (M(r) 90,000-116,000) revealed the presence of several potential
      sites for glycan substitution on a protein backbone of M(r) approximately 66,500,
      and identity with chitinases. In order to further define the nature of the
      secreted glycoprotein, the objectives of the present study were 1) to devise a
      method to significantly enrich for the glycoprotein from oviductal secretions, 2)
      to biochemically characterize the glycoprotein by use of lectin blotting and
      enzymatic and chemical digestion, and 3) to determine whether unfractionated and
      enriched fractions containing the glycoprotein have chitinase activity. Oviducts
      were obtained from ovariectomized ewes treated with estradiol for 6 days and
      explant-cultured for 24 h. The oviductal glycoprotein was enriched approximately
      80-85% from explant culture media by Maackia amurensis agglutinin (MAA) lectin
      affinity chromatography. Enriched fractions containing the oviductal protein were
      separated on SDS gels, transferred to polyvinyl difluoride, and probed with
      digoxigenin-labeled lectins. Lectin blotting revealed that the glycoprotein
      contained the carbohydrate moieties N-acetylgalactosamine, N-acetylglucosamine,
      galactose, fucose, and sialic acid both in alpha(2,3) and alpha(2,6) linkages,
      typical of sialomucins. Enzymatic digestion with neuraminidase and N-glycanase
      indicated that approximately 20% and approximately 6% of the molecular weight of
      the oviductal glycoprotein can be accounted for by sialic acid and N-linked
      glycans, respectively. The oviductal glycoprotein was resistant to digestion with
      O-glycanase alone and chondroitinase ABC, with the latter indicating that it was
      not a proteoglycan. Treatment with trifluoromethanesulfonic acid resulted in a
      deglycosylated product of M(r) approximately 66,000 immunoreactive with
      antibodies to the oviductal glycoprotein. No chitinase activity could be detected
      for unfractionated culture medium proteins or enriched fractions containing the
      M(r) 90,000-116,000 oviductal glycoprotein when the substrate methylumbelliferyl
      chitotriose was used. These data show that 1) MAA lectin chromatography can
      significantly enrich for the M(r) 90,000-116,000 glycoprotein from oviductal
      secretions, 2) the secreted glycoprotein contains saccharide residues typical of
      sialomucins, and 3) despite primary amino acid sequence identity, the oviductal
      glycoprotein does not share an enzymatic relationship with chitinases.

PMID- 8562711
TI  - Temporal and spatial alterations in uterine estrogen receptor and progesterone
      receptor gene expression during the estrous cycle and early pregnancy in the ewe.
AB  - Mechanisms regulating responses of the ovine uterus to endocrine and paracrine
      signals during the estrous cycle and pregnancy are likely to require tissue- and
      cell-specific regulation of steroid hormone receptor gene expression. To
      determine effects of day and pregnancy status (cyclic or pregnant) on uterine
      estrogen receptor (ER) and progesterone receptor (PR) gene expression, ewes were
      hysterectomized either on Day 1 (Day 0 = estrus/mating), 6, 11, 13, or 15 of the
      estrous cycle (n = 3/day) or on Day 11, 13, 15, 17, or 25 of early pregnancy (n =
      5/day). Steady state levels of ER and PR mRNA were determined in endometrial and
      myometrial tissues by slot-blot hybridization and ribonuclease protection assays,
      respectively, using homologous ovine ER and PR cRNA probes. Changes in spatial
      expression of ER and PR mRNA and protein in uterine tissue sections were
      determined by in situ hybridization and immunocytochemical analyses. In cyclic
      ewes, steady state levels of endometrial ER mRNA were highest on Day 1, declined
      between Days 1 and 6, and increased between Days 11 and 15. However in pregnant
      ewes, endometrial ER mRNA levels decreased between Days 11 and 15 and increased
      slightly between Days 15 and 25. In cyclic ewes, levels of myometrial ER mRNA
      were highest on Day 1, decreased to Day 6, and remained low thereafter. In cyclic
      ewes, endometrial PR mRNA levels were highest on Day 1, decreased between Days 1
      and 11, and then increased between Days 13 and 15. In cyclic ewes, myometrial PR
      mRNA levels were highest on Day 1 and declined thereafter. Endometrial PR mRNA
      levels were not different between cyclic and pregnant ewes on Days 11, 13, and
      15. In pregnant ewes, PR mRNA levels were low on Day 11, increased between Days
      11 and 17, and decreased between Days 17 and 25. In pregnant ewes, myometrial PR
      mRNA levels were low and did not change between Days 11 and 25. In situ
      hybridization and immunocytochemical analyses revealed distinct tissue- and cell
      type-specific alterations in uterine ER and PR mRNA and protein expression during
      the estrous cycle and early pregnancy that generally paralleled overall changes
      in steady state levels of ER and PR mRNAs. In the endometrium, the most striking
      observation was that PR mRNA and protein expression disappeared from the luminal
      and shallow glandular epithelium between Days 6 and 13 of the estrous cycle,
      whereas ER mRNA and protein expression was low on Days 6 and 11 and increased
      between Days 11 and 15 in the luminal and shallow glandular epithelium. During
      early pregnancy, expression of ER and PR mRNAs, as well as ER and PR protein, was
      very low or absent in the luminal and shallow glandular epithelium between Days
      13 and 25 of pregnancy. Moreover, ER and PR mRNA and protein were consistently
      present at low levels in the stroma and deep glandular epithelium in both cyclic
      (Days 11-15) and pregnant (Days 11-25) ewes. Collectively, results suggest that
      uterine ER and PR gene expression is regulated in a tissue- and cell type
      specific manner during the estrous cycle and early pregnancy.

PMID- 8562712
TI  - [Ventilator weaning].

PMID- 8562713
TI  - [Gamma-hydroxybutyric acid--significance for anesthesia and intensive care
      medicine?].
AB  - Gamma-hydroxybutyric acid (GHB) as a natural component of the mammalian brain was
      first introduced in clinical anaesthetic practice more than 30 years ago.
      Although GHB induced a reliable state of sedation and anaesthesia without
      depressing either respiratory or cardiocirculatory parameters or liver and kidney
      function, the drug was nearly displaced from clinical practice because of its
      prolonged duration of action. The results of recent clinical studies indicate a
      re-evaluation of GHB in emergency and critical care medicine. GHB is regarded as
      a natural neuronal transmitter with circuits which synthesise, accumulate and
      release GHB. Specific binding sites have also been demonstrated and identified.
      GHB is completely metabolized in the liver to the natural substrates carbon
      dioxide and water without accumulation in central or peripheral tissues. The
      reduction of energy metabolism and its possible properties as an "oxygen radical
      scavenger" may be of therapeutic benefit if tissues are exposed to hypoxia or
      reperfusion. Therefore, the application of GHB seems to be of advantage in states
      of traumatic brain injury with cerebral oedema or ischaemic lesions of brain or
      extraneural tissues. In hypovolaemic states or in patients with impaired
      cardiovascular function, the pressure effects of GHB may be beneficial for the
      prevention of tissue damage and may improve survival in the case of
      cardiocirculatory resuscitation. In the intensive care unit, GHB might be a
      favourable alternative to established sedative agents. Occurrence of side effects
      such as tolerance and withdrawal syndromes after the application of sedative
      drugs, an impaired metabolism with the accumulation of metabolites in the case of
      liver or kidney dysfunction as well as an insufficient regulation of natural
      sleep may be diminished by the application of GHB. The results of various
      clinical studies also suggest that GHB may be useful in the treatment of alcohol
      and opiate withdrawal syndrome. However, further studies are necessary to specify
      the proposed indications of GHB in anaesthesiology and critical care medicine.

PMID- 8562714
TI  - [Ventilator weaning after long-term ventilation--the concept of a regional
      ventilator weaning center].
AB  - Long-term mechanical ventilation implies a significant number of weaning
      failures. The basis of this unweanability is chronic fatigue of the inspiratory
      muscles which is due to depletion of energy store (e.g. glycogen). Considering
      this pathophysiological principle, the decisive therapeutic option during weaning
      from long-term mechanical ventilation consists of resting the respiratory
      muscles. The commonly used assisted ventilation modes only partially relieve the
      respiratory muscles because the work of breathing is done both during the trigger
      phase and during the inspiratory cycle. The essential characteristic of our
      weaning concept includes the repeated determination of the spontaneous breathing
      frequency in awake patients, which is followed by controlled intermittent
      positive pressure ventilation with a slightly higher respiratory rate. Ideally,
      this results in total suppression of the activity of the breathing centre, and in
      subsequent relief and recovery of the respiratory muscles by replenishing the
      energy stores. The close succession of relief and training periods avoids
      inactivity-induced atrophy of the respiratory muscles and permits regeneration.
      Additionally, our weaning concept avoids increases in inspiratory work during the
      phases of spontaneous breathing. This means that high-resistance small-caliber
      endotracheal tubes have to be replaced by large tubes. Moreover, transtracheal
      oxygen insufflation during spontaneous breathing decreases anatomic dead space.
      This reduces minute ventilation and, therefore, the work of breathing. In
      patients still exhibiting chronic fatigue of the respiratory muscle pump after
      successful weaning, intermittent home ventilation is initiated via a breathing
      mask. Apart from the concept described above, successful weaning from the
      respirator after long-term ventilation is based upon dedicated patient care and
      depends on the architectural characteristics of the intensive care unit.

PMID- 8562715
TI  - [Pharmacokinetics of buprenorphine in subcutaneous administration].
AB  - In this study investigations were carried out on pharmacokinetics of
      buprenorphine after it had been applied subcutaneously. Up to now no
      pharmacokinetic data exist using this kind of application with relevant clinical
      doses. METHODS: With 6 patients, who had major general surgery under balanced
      anaesthesia, buprenorphine was given in a single subcutaneous injection of 5
      micrograms/kg bodyweight for postoperative pain relief. Over a period of 48 hours
      the level of buprenorphine in blood plasma was measured. The analyses were done
      with a modified HPLC method with electrochemical detection which is able to
      achieve measurements as low as 40 pg/ml of plasma. The pharmacokinetic values
      were calculated with the "Topfit" pharmacokinetic computerised programme.
      RESULTS: Whereas the period of time (tmax) to reach peak plasma concentration
      (Cmax) after subcutaneous application is much longer than with other parenteral
      application forms, the plasma concentration levels tend to be similar after 20
      minutes. The most important finding of this study is that the mean terminal half
      life (t1/2c) of buprenorphine is 23 hours. However, the presently available data
      for other application forms in respect to terminal half-life did not produce the
      same results. This can be explained by the use of insufficiently sensitive
      analytical procedures and by too short periods of observation of 3 and 13 hours
      respectively, leading to values of t1/2c of 2 and 5 hours. CONCLUSIONS: These
      results indicate that the terminal half-life (t1/2c) of buprenorphine is much
      longer than had been supposed. It confirms clinical findings of sufficient pain
      relief by showing measurable uptake of buprenorphine after subcutaneous
      application.

PMID- 8562716
TI  - [Thrombomodulin as endothelial cell marker in heart surgery patients].
AB  - OBJECTIVE: Thrombomodulin is a high-affinity receptor for thrombin on the
      endothelial cell surface. The aim of our study was to investigate whether plasma
      thrombomodulin represents a marker of endothelial injury following
      cardiopulmonary bypass. METHODS: Plasma levels of thrombomodulin were quantitated
      in 70 plasma samples obtained from 14 adult cardiac patients undergoing
      hypothermic pulsatile low-flow low-pressure cardiopulmonary bypass. Blood samples
      were taken before cardiopulmonary bypass (T1), and 15 minutes (T2), 1 hour, 6
      hours, and 20 hours after termination of bypass. Plasma thrombomodulin was
      quantitated with a sandwich enzyme-linked immunosorbent assay (ELISA).
      Statistical analysis was performed by the Friedman and Wilcoxon tests. RESULTS:
      Plasma thrombomodulin was significantly elevated 20 hours after discontinuation
      of cardiopulmonary bypass, when compared with T1 and T2. CONCLUSION: We conclude
      from our results that a moderate elevation of plasma thrombomodulin is seen in
      adult patients following hypothermic, low-flow low-pressure cardiopulmonary
      bypass, which may reflect endothelial injury. Circulating thrombomodulin levels
      are thus possibly useful for assessment of endothelial damage occurring in
      patients undergoing cardiopulmonary bypass.

PMID- 8562717
TI  - [Extracorporeal membrane oxygenation of the newborn infant--an example of
      interdisciplinary project management].
AB  - In the last three years an interdisciplinary ECMO (extracorporeal membrane
      oxygenation) team has been set up at the Free University of Berlin in the
      Steglitz clinic. With this form of management, newborns only a few hours or days
      old who present with pulmonary failure can temporarily be managed with
      extracorporeal oxygenation until normal lung function is restored. The set up of
      this ECMO team, starting with experimental training in animal models, to the
      bedside clinical use is discussed. The following presentation of the first four
      cases managed here with ECMO aims to clarify the problems which may be
      encountered as well as amplifying its use as a life-saving measure.

PMID- 8562718
TI  - [Otto Kappeler--a pioneer in anesthesia in German-speaking regions].
AB  - The publication of textbooks on anaesthesiology reflects the enormous progress
      made over the last decades. This new branch of medicine was first completely
      described in Germany by Otto Kappeler from Switzerland, who was asked to do so by
      his famous colleague Theodor Billroth from Vienna. Starting with remarks
      concerning the history of anaesthesiology, he described on more than 220 pages
      everything that was known about the anaesthetics used at that time. Additionally,
      he outlined the prospects of the then also brand new methods of local
      anaesthesia. Undoubtedly it was of Kappeler's special concern to avoid the risk
      of iatrogenic complications while the patient was under any anaesthetic. This can
      easily be proved by the fact that he put special emphasis on precautions
      concerning life-threatening situations and their therapy. To avoid the dangers of
      an acute airway obstruction by the patient's tongue, he modified the so-called
      "Esmarch-Heidberg" manoeuvre, which later on became known as the "Kappeler"
      flick. For the first time ever, Kappeler managed to describe sphygmographically
      the circulatory effects of narcotics in an anaesthesia-related textbook.
      Basically, he could not find any differences between them, since " ... all higher
      dosages of anaesthetics used during operations caused ... a strong widening of
      the blood vessels ... by paralysing the vasoconstrictors". He believed it would
      be possible to exclude the dangers of overdosing drugs by introducing devices to
      perform anaesthesia. In using his self-designed device, which was a modification
      of the device used at that time, invented by Junker, he was able to come closer
      to the goal of "in somno securitas" he so vehemently fought for. This confidence
      he derived from the fact that he was already a strong believer in the advantage
      of the "self-conducted chloroformation or anaesthesia".

PMID- 8562719
TI  - [Laparoscopic surgery--surgical and anesthesiological status].

PMID- 8562720
TI  - [Status of laparoscopic cholecystectomy].

PMID- 8562721
TI  - [Is laparoscopic intestinal resection for oncologic indications possible?].

PMID- 8562723
TI  - [Cardiovascular function during laparoscopic interventions in surgery and
      gynecology].

PMID- 8562722
TI  - [Laparoscopic surgery of benign small and large intestinal diseases].

PMID- 8562724
TI  - [Anesthesiologic procedures in laparoscopic cholecystectomy].

PMID- 8562725
TI  - [Polytrauma and malignant neuroleptic syndrome. Case presentation with diagnostic
      problems].
AB  - The neuroleptic malignant syndrome (NMS) is a rare but potentially fatal reaction
      associated with neuroleptic drugs. The role of an acute reduction in brain
      dopamine activity in the development of NMS is commonly accepted as underlying
      pathogenesis. The diagnosis is maintained by the classic findings of
      extrapyramidal signs, hyperthermia and autonomic dysfunction. Treatment consists
      primarily of early recognition and discontinuation of triggering drugs. We report
      on a young patient with an acute paranoid schizophrenia who suffered a severe
      polytrauma due to a jump from 10 m height initiated by acoustic hallucinations.
      The patient received haloperidol for psychotic symptoms in a dose of up to 65
      mg/d and chlorprothixene. NMS developed during the second week after the
      polytrauma. Discontinuation of neuroleptic therapy was followed by complete
      recovery. The report underlines problems of diagnosis due to the ambiguity of the
      diagnostic criteria of neuroleptic malignant syndrome in the presence of
      polytrauma.

PMID- 8562726
TI  - [Report on the 22nd Neonatal and Infant Respiratory Symposium in Veil, Colorado,
      1995].

PMID- 8562727
TI  - [Comment on: Legal outcome of crime under anesthesia].

PMID- 8562728
TI  - Nomenclature for aerobic and facultative bacteria.

PMID- 8562729
TI  - Microbiology terminology update: clinically significant anaerobic gram-positive
      and gram-negative bacteria (excluding spirochetes).

PMID- 8562730
TI  - Selected medically important fungi and some common synonyms and obsolete names.

PMID- 8562731
TI  - Viral taxonomy.

PMID- 8562732
TI  - Classification of human parasites, vectors, and similar organisms.

PMID- 8562733
TI  - An overview of human brucellosis.

PMID- 8562734
TI  - Diagnostic mycobacteriology laboratory practices.
AB  - The resurgence of tuberculosis has forced clinical laboratories to improve the
      methods used for detection of M. tuberculosis. Current recommendations for
      diagnostic laboratory performance [7] include (1) daily processing of specimens
      (i.e., handling these specimens in the same way that all other specimens sent to
      the laboratory are handled); (2) inoculation of liquid media (e.g., BACTEC) for
      the primary culture; (3) use of nucleic acid probes or the NAP test for
      identifying isolates as M. tuberculosis as soon as possible; (4) determining drug
      susceptibility with use of liquid media; and (5) reporting results of each step
      to physicians in a timely manner. The immediate goals are to report
      identification of M. tuberculosis within 10-14 days of receipt of the specimen
      and to report drug susceptibilities within 15-30 days. This can be done if
      current technologies are fully utilized. The amplification-based systems for the
      identification of M. tuberculosis and the luciferase-based systems for rapid
      determination of drug susceptibilities should help further shorten turn-around
      times. The results to date demonstrate that these systems are feasible, although
      they must be reduced to formats that can be used routinely in clinical
      laboratories. The gene-amplification systems may be the most promising, and they
      are nearing commercial availability. If the assays function as well during
      routine use as they have during clinical trials, a clinical laboratory may soon
      be able to report confirmed M. tuberculosis infection to the physician within
      hours of receiving a specimen, instead of within the typical period of 2-4
      weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562735
TI  - Magnetic resonance imaging of the brain in patients with cerebral malaria.
AB  - In a prospective study of cerebral malaria, 24 adults with this disease underwent
      magnetic resonance imaging (MRI) of the brain. Four patients died. Two of these
      patients (nos. 17 and 24) had breathing abnormalities requiring ventilatory
      support followed by clinical signs of brain death. Four days later MRI of patient
      17 showed gross swelling of the brain, and 5 hours later MRI of patient 24 showed
      foramen magnum herniation. Twenty-two patients had no evidence of cerebral edema,
      but MRI revealed that brain volume during acute cerebral malaria was slightly
      greater than that during the convalescent phase of the disease. This difference
      was attributed to an increase in the volume of intracerebral blood. The cerebral
      volume was lower during early convalescence than several months later. The volume
      of the brain in patients with cerebral malaria is increased. This increased
      volume probably results from sequestration of parasitized erythrocytes and
      compensatory vasodilatation rather than from edema. Brain stem herniation may
      occur, but its temporal relation to brain death in cases of cerebral malaria
      remains uncertain.

PMID- 8562736
TI  - Lower respiratory tract infections following cardiac arrest and cardiopulmonary
      resuscitation.
AB  - All episodes of lower respiratory tract infection that developed among 96
      patients surviving for > 24 hours after cardiac arrest were prospectively studied
      over an 18-month period. Pneumonia developed in 23 (24.0%) of patients after a
      mean of 7 days (SD, +/- 6.2 days). The development of four superinfections raised
      the cumulative incidence to 28.1%. Purulent tracheobronchitis was diagnosed in
      three instances. The causative agent of pneumonia was identified in 18 episodes,
      three of which were polymicrobial. Gram-positive cocci represented 57.1% of
      isolates, and Staphylococcus aureus--the most frequently isolated microorganism
      in this population--accounted for two-thirds of all gram-positive cocci.
      Pseudomonas aeruginosa was isolated in six episodes, five of which were
      associated with previous antibiotic use. Nine (39.1%) of the 23 patients in the
      group with pneumonia died, but only one of these deaths was considered to be
      directly related to pneumonia. In conclusion, pneumonia is a common complication
      of patients surviving cardiac arrest, but, with adequate treatment, its influence
      on outcome is marginal. Gram-positive cocci are the predominant pathogens,
      although infection with P. aeruginosa should be considered among patients
      receiving antibiotics.

PMID- 8562737
TI  - Photo quiz. Rocky Mountain Spotted Fever.

PMID- 8562738
TI  - Prevalence of asymptomatic bacteriuria and associated host factors in women with
      diabetes mellitus. The Manitoba Diabetic Urinary Infection Study Group.
AB  - A prospective study was undertaken to determine the prevalence of significant
      asymptomatic bacteriuria in adult women with diabetes mellitus attending
      endocrinology clinics at two tertiary-care university-affiliated teaching
      hospitals. In addition, host factors of the patients were correlated with
      bacteriuria. The overall prevalence of bacteriuria was 7.9% (85 cases per 1,072
      women). Absolute urinary leukocyte (white blood cell) counts were > or = 10/mm3
      in 77.6% (66) of the 85 bacteriuric women vs. 23.7% (234) of the 987
      nonbacteriuric women (P < .001). Bacteriuric women were significantly more likely
      than nonbacteriuric women to have non-insulin-dependent diabetes mellitus, longer
      duration of diabetes, neuropathy, and heart disease. Aboriginals had bacteriuria
      at a significantly higher prevalence rate than that among nonaboriginals (19.7%
      [15 of 76] vs. 7.0% [70 of 996], respectively; P < .0001), were more likely to
      have occult upper urinary tract infection (antibody-coated bacteria positivity:
      53% [8 of 15] vs. 20% [10 of 50], respectively; P = .016), and had significantly
      lower urinary leukocyte counts, whether they were bacteriuric or not (P < .05).
      Multivariate analysis identified duration of diabetes and aboriginal origin as
      independent risk factors for the presence of bacteriuria.

PMID- 8562739
TI  - Meningitis caused by Candida species: an emerging problem in neurosurgical
      patients.
AB  - Three cases of candida meningitis were encountered in a 3-year period in our
      hospital; all occurred in neurosurgical patients. We describe these three cases
      and review the 15 cases of neurosurgery-related candida meningitis previously
      reported in the English-language literature. Data regarding these 18 patients
      formed the basis for our review. Most patients with candida meningitis had
      recently received antibacterial agents, and it is notable that 50% of patients
      suffered from antecedent bacterial meningitis. The CSF analysis revealed
      neutrophilic pleocytosis that was indistinguishable from that of bacterial
      meningitis. The overall mortality was 11%. Administration of amphotericin B
      combined with flucytosine appeared to be the best therapeutic approach for
      candida meningitis.

PMID- 8562740
TI  - Familial carriage of methicillin-resistant Staphylococcus aureus and subsequent
      infection in a premature neonate.
AB  - During routine surveillance of patients in a Neonatal Intensive Care Unit (NICU),
      an alert infection-control practitioner confirmed the relationship of the index
      patient (sibling 3) who had a methicillin-resistant Staphylococcus aureus (MRSA)
      infection to an infant sibling (sibling 2) who had been admitted to the hospital
      7 months previously with an MRSA infection. Cultures of nasal specimens obtained
      from the index patient's parents and two other siblings also yielded MRSA for two
      of the family members, the mother and sibling 1. The strains were typed by
      antibiogram, plasmid analysis, and genomic DNA typing. The isolates from sibling
      1, sibling 2, the mother, and one isolate from sibling 3 were found to be
      identical by all techniques. The other isolates from sibling 3 shared the same
      genomic type but had no detectable plasmids. These findings suggest that
      transmission of this strain occurred at least three times within this family and
      that at least one family member was colonized with the same strain for 7 months
      or more. Recognition that family members may serve as reservoirs for nosocomial
      infections with MRSA raises important issues for infection control.

PMID- 8562741
TI  - Clinical and microbiological characteristics of severe group A streptococcus
      infections and streptococcal toxic shock syndrome.
AB  - We have monitored all cases of invasive group A streptococcus (GAS) infection
      that have occurred at the New York Hospital (New York) since 1989. Five cases of
      GAS infection and shock were identified between 1990 and 1991, and an additional
      case was recently identified at an affiliated hospital. Five of the six patients
      met the case definition for streptococcal toxic shock syndrome (strep TSS). Three
      were bacteremic, and four had aggressive soft-tissue infections. Patients with
      shock, for whom the mortality was higher, had fewer underlying illnesses than did
      patients who had GAS bacteremia without shock. Although the M1 serotype and
      production of streptococcal pyrogenic exotoxin A were more common in patients
      with GAS infection and shock, several patients with strep TSS were infected with
      a nontypable strain of GAS that produced only streptococcal pyrogenic exotoxin B.
      In addition, we observed a distinctive early hemodynamic profile for patients
      with strep TSS that was unlike that for patients who had typical gram-negative
      septic shock; this profile was consistent with toxic cardiomyopathy (i.e.,
      relatively low cardiac output, low-to-normal systemic vascular resistance, and
      striking reduction in ventricular performance.

PMID- 8562742
TI  - Zaldaride maleate (a new calmodulin antagonist) versus loperamide in the
      treatment of traveler's diarrhea: randomized, placebo-controlled trial.
AB  - The present study was undertaken to compare the efficacy of a new calmodulin
      antagonist, zaldaride maleate, with that of placebo or loperamide in persons with
      traveler's diarrhea. One hundred seventy-nine patients were randomized to receive
      loperamide (4 mg followed by 2 mg after each unformed stool), zaldaride maleate
      (20 mg four times per day), or placebo. During the initial 48 hours of therapy,
      zaldaride maleate decreased the number of unformed stools by 30% and the duration
      of illness by 23% when compared with placebo. Loperamide was superior to both
      zaldaride maleate and placebo during the initial hours of treatment. However,
      after 48 hours of treatment, loperamide and zaldaride maleate were equally
      efficacious, decreasing by > 50% the number of unformed stools passed in a 24
      hour interval (P, not significant), and were both superior when compared with
      placebo (P < .0001 and P = .0048, respectively). The apparent superiority of
      loperamide early in the course of therapy appeared to be related to a loading
      dose effect and not to any differences in antidiarrheal properties.

PMID- 8562743
TI  - Pneumococcal bacteremia in adults: a 14-year experience in an inner-city
      university hospital.
AB  - We retrospectively reviewed 304 episodes of pneumococcal bacteremia in 293 adults
      to compare the clinical features, prognostic factors, and case-fatality rate
      associated with this illness to those in previous studies. We studied patients at
      an inner-city university hospital who had pneumococcal bacteremia from January
      1980 through December 1993. We analyzed patient demographics, risk factors for
      pneumococcal infection, pneumococcal vaccination status, initial vital signs,
      findings on chest roentgenograms, arterial blood gases, and laboratory values.
      Ninety-six percent of our study population was African American and 61% were
      male; pneumococcal vaccination was documented for 2%. The case-fatality rate in
      our study was 36%. Older age, lower mean arterial pressure, lower mean
      temperature, higher respiratory rate, multilobar pneumonia, leukopenia, low
      platelet count, hypoalbuminemia, low arterial pH, low arterial oxygen tension,
      and high arterial carbon dioxide tension were associated with higher mortality.
      Our study suggests that mortality due to pneumococcal bacteremia has not changed
      significantly in the last 6 decades, that the number of patients in high-risk
      groups who are receiving pneumococcal vaccine is insufficient, and that higher
      mortality can be predicted from the history, vital signs, and laboratory values
      at initial presentation.

PMID- 8562744
TI  - Neuroretinitis, aseptic meningitis, and lymphadenitis associated with Bartonella
      (Rochalimaea) henselae infection in immunocompetent patients and patients
      infected with human immunodeficiency virus type 1.
AB  - Bartonella (Rochalimaea) henselae causes a variety of diseases, including
      bacillary angiomatosis, peliosis hepatis, lymphadenitis, aseptic meningitis with
      bacteremia, and cat-scratch disease (CSD). Cases of B. henselae-related disease
      were collected from September 1991 through November 1993. Patients with suspected
      CSD, unexplained fever and lymphadenitis, or suspected B. henselae infection who
      were seen in the Infectious Diseases Clinic at Wilford Hall Medical Center
      (Lackland Air Force Base, TX) underwent physical and laboratory examinations. In
      addition to three previously described cases, 23 patients with R. henselae
      related infection were identified. The patients included 19 immunocompetent
      individuals presenting with lymphadenitis (11), stellate neuroretinitis (5),
      Parinaud's oculoglandular syndrome with retinitis (1), chronic fatigue syndrome
      like disease (1), and microbiologically proven adenitis without the presence of
      immunofluorescent antibodies to B. henselae (1) and four patients infected with
      human immunodeficiency virus type 1 presenting with isolated lymphadenitis (1),
      diffuse upper-extremity adenitis (1), neuroretinitis (1), and aseptic meningitis
      (1). A couple with neuroretinitis and their pet cat, a persistently fatigued
      patient, and a patient with Parinaud's oculoglandular syndrome were shown to have
      bacteremia. Tissue cultures were positive for B. henselae in three recent cases
      of adenitis. Twenty-two patients were exposed to cats. This series further
      demonstrates the similarities between B. henselae-related diseases and CSD and
      identifies several new syndromes due to B. henselae.

PMID- 8562745
TI  - Invasive fungal disease in adults undergoing remission-induction therapy for
      acute myeloid leukemia: the pathogenetic role of the antileukemic regimen.
AB  - Using multivariate techniques, we studied the relationships of cytotoxic regimen,
      intestinal mucosal damage, and fungal colonization in the pathogenesis of
      invasive fungal disease in 138 patients undergoing induction therapy for
      untreated acute myeloid leukemia (AML) according to three institutional
      protocols: AML-84 (cytarabine/daunorubicin), AML-87 (high-dose
      cytarabine/etoposide/daunorubicin), and AML-88 (mitoxantrone/etoposide). Invasive
      fungal disease occurred in 36%, 6%, and 2.6% of patients participating in
      protocols AML-87, AML-84, and AML-88, respectively (chi 2 = 23.465; P < .0001).
      Protocol AML-87 was the strongest independent predictor in the multivariate model
      (RR = 26.7; P < .0001). Cytotoxic therapy-related epithelial damage in the gut,
      as measured by D-xylose malabsorption, correlated with invasive fungal disease
      and protocol AML-87. Fungal colonization, a predictor of invasive fungal disease,
      correlated with frequent modifications of antibiotic regimens. These results
      demonstrate the role of cytotoxic regimen-related gut epithelial damage,
      antibiotic-prescribing behavior, and fungal colonization in the pathogenesis of
      invasive fungal disease in patients with leukemia.

PMID- 8562746
TI  - Clinical spectrum of herpes zoster in adults infected with human immunodeficiency
      virus.
AB  - To determine the incidence and clinical manifestations of herpes zoster in a
      hospital-based clinic for adults infected with human immunodeficiency virus
      (HIV), we reviewed the records of all patients for whom zoster was diagnosed at
      or after their first clinic visit. Fifty-two episodes of zoster occurred in 45
      patients during 1,614 person-years of follow-up (incidence, 3.2 episodes per 100
      person-years). The following major complications of zoster occurred in 12
      patients (27%): ocular complications (5), neurological complications (4), and
      chronic atypical skin lesions (5). Six patients each had postherpetic neuralgia
      and bacterial superinfection, which were the common minor complications of
      zoster. Multivariate analysis revealed that only a low CD4 cell count (< or =
      200/mm3) was predictive of a major complication of zoster (OR, 13.2; 95% CI, 1.52
      114; P = .019). Thus, complications of herpes zoster are common in patients with
      HIV infection, especially those with advanced immunosuppression.

PMID- 8562747
TI  - Respiratory syncytial virus pneumonia in hospitalized adult patients with
      leukemia.
AB  - Respiratory syncytial virus (RSV) has been demonstrated to be an important cause
      of life-threatening pneumonia in adult bone marrow transplant recipients;
      however, its role in other immunocompromised adults has not been defined. We
      prospectively studied all adult patients with leukemia who were hospitalized at
      M. D. Anderson Cancer Center (Houston) during a 1-year period (November 1993
      through October 1994). During a 19-week period when RSV was prevalent in the
      community, it was isolated from 9 (10%) of 87 patients with leukemia who
      developed an acute respiratory illness. In 6 (75%) of 8 patients with profound
      chemotherapy-induced myelosuppression, the RSV infection was complicated by
      pneumonia, with an 83% mortality rate. RSV appears to be an important cause of
      severe and often fatal pneumonia in myelosuppressed patients with leukemia.

PMID- 8562748
TI  - Persistence of Borrelia burgdorferi sensu lato in resolved erythema migrans
      lesions.
AB  - Erythema migrans skin lesions resulting from a tick bite and infection with
      Borrelia burgdorferi sensu lato eventually resolve, even without antibiotic
      therapy. The aim of the present study was to gauge the frequency of persistence
      of B. burgdorferi sensu lato in such lesions. Thus, the site of a previous lesion
      was biopsied and cultured in 48 patients: 39 with systemic or localized
      symptoms/signs and nine with no symptoms. B. burgdorferi sensu lato was isolated
      from biopsied skin from three symptomatic patients. Cultures of other tissues and
      fluids were negative. By genospecies-specific polymerase chain reaction (PCR) and
      pulsed-field gel electrophoretic (PFGE) analysis, two isolates were classified as
      Borrelia afzelii. The remaining isolate was a member of an unusual group of
      strains that type as B. burgdorferi sensu stricto by genospecies PCR but possess
      an atypical PFGE profile. All three patients had a dramatic clinical response to
      antibiotic treatment. These findings demonstrate the capacity of viable B.
      burgdorferi sensu lato organisms to persist in clinically normal-appearing skin
      at the site of a resolved erythema migrans rash for periods ranging from 2 months
      to 3.5 years. This observation may provide new insight into the organisms'
      ability to evade the host's immune response.

PMID- 8562749
TI  - Spectrum and significance of bacteremia due to Moraxella catarrhalis.
AB  - Fifty-eight cases of bacteremia due to Moraxella catarrhalis, including seven
      that occurred in patients treated at our facilities, are analyzed. The host's
      medical history plays a major role in the presentation and outcome of M.
      catarrhalis bacteremia. Bacteremia is typically accompanied by pneumonia in
      adults with underlying respiratory disease. Many neutropenic patients do not
      manifest a focus of infection; in contrast, the source identified in healthy,
      immunocompetent patients is usually the upper airway or the ears. In the recent
      literature, it has been reported that a rash is typically absent in adults with
      bacteremic pneumonia and in immunocompetent hosts and that only some neutropenic
      patients have a rash. The prognosis is grave for patients with endocarditis and
      for patients with immunoglobulin deficiency or neutropenia not related to a
      hematologic malignancy. In addition, mortality is substantial among bacteremic
      patients with respiratory conditions or other chronic debilities, especially when
      respiratory copathogens are present. The prognosis is good for febrile
      neutropenic patients with underlying leukemia or lymphoma when the neutropenia
      resolves. When healthy, immunocompetent individuals are affected with M.
      catarrhalis bacteremia, their presentations range from self-limited febrile
      illness to life-threatening disease.

PMID- 8562750
TI  - Tuberculosis in heart transplant recipients.
AB  - We present an analysis of the incidence, clinical presentation, and evolution of
      tuberculosis in heart transplant recipients at a 2,200-bed tertiary care center
      in Madrid and review the world literature. During a 5-year period (1989-1993),
      active extrapulmonary tuberculosis was diagnosed in three of the 144 patients who
      survived heart transplantation, resulting in an incidence of 1.35 cases per 100
      heart transplant-years (> 20-fold the national average). The mean age of the
      patients was 52 years, and two were male. The mean time to development of
      tuberculosis after transplantation was 76 days (range, 55-102 days). All of the
      patients had had previous episodes of rejection and infection and had had
      initially negative tuberculin tests (one converted to positive during therapy).
      Clinical manifestations were mild or absent in two of the patients, and
      Mycobacterium tuberculosis was isolated in association with other microorganisms
      from two patients. All patients were successfully treated with antituberculous
      chemotherapy while they were receiving immunosuppressants. A severe drug
      interaction between cyclosporine and rifampin in the first case necessitated
      withdrawal of rifampin and precluded its use in subsequent patients. During a
      mean follow-up of 2 years, no recurrence of tuberculosis has been detected in any
      of the patients. Tuberculosis was diagnosed in a fourth patient before
      transplantation, which was performed while the patient was receiving
      antituberculous therapy. Our data support the conclusion that heart
      transplantation should be considered an unheralded risk factor for tuberculosis,
      particularly in countries where this disease is prevalent.

PMID- 8562751
TI  - Infections complicating tunneled intraspinal catheter systems used to treat
      chronic pain.
AB  - Tunneled intraspinal catheters and catheter-pump systems are increasingly common
      treatments for severe chronic pain, but these long-term catheters have caused
      meningitis, epidural abscesses, and other serious infections. At a cancer
      referral center, 81 catheters were placed in 72 patients over a 7-year period.
      There were seven catheter-associated infections: two were meningeal (one was
      accompanied by an epidural abscess and one by a pocket infection and bacteremia),
      four were associated with a pocket, and one was associated with a tunnel. The
      infection rate was 0.77 per 1,000 catheter-days. Pathogenic organisms that were
      isolated were primarily normal skin flora. By multivariate Cox analysis, the only
      factor significantly associated with catheter infection was prolonged catheter
      placement surgery, i.e., a procedure lasting at least 100 minutes (RR, 8.8; 95%
      CI, 1.6-50). Three patients were cured by removal of the catheter and treatment
      with antibiotics, and symptoms were satisfactorily suppressed in four patients
      with antibiotics alone. Considering the severity of illness in catheter
      recipients, the infection rate was relatively low. Removal of the catheter does
      not appear mandatory when the goal is suppression of infection-related symptoms,
      especially when the infection has not spread to the CNS, the infecting organism
      has an intrinsically low virulence, and the infected patient is terminally ill.

PMID- 8562752
TI  - Comparison of azithromycin and ceftriaxone for the treatment of chancroid.
AB  - We conducted a randomized, unblinded, prospective study designed to determine the
      efficacy of single-dose azithromycin for the treatment of chancroid. Men and
      women 16 years of age and older who had darkfield-negative genital ulcers that
      were clinically suspected to be caused by Haemophilus ducreyi and who attended
      urban sexually transmitted disease clinics or presented to hospital emergency
      departments were enrolled in the study. Patients were randomized to receive 250
      mg of ceftriaxone im or 1 g of azithromycin orally, both given as a single dose.
      They were followed for up to 23 days after treatment. For 65 patients, cultures
      were positive for H. ducreyi; there were 68 patients whose cultures were negative
      for both H. ducreyi and herpes simplex virus and who had no evidence of syphilis.
      All 133 patients returned for at least one follow-up visit. At the time of the
      last follow-up visit, all 32 patients whose cultures were positive for H. ducreyi
      and who were treated with azithromycin were clinically cured. In all 33 culture
      positive cases in which ceftriaxone was used, there was either clinical
      improvement or cure at the time of the patient's last follow-up visit. In
      addition, azithromycin and ceftriaxone were equally effective in healing ulcers
      for which cultures were negative. We conclude that a single 1-g oral dose of
      azithromycin is as effective as a 250-mg im dose of ceftriaxone for the treatment
      of chancroid.

PMID- 8562753
TI  - Thrombocytopenia in patients infected with human immunodeficiency virus:
      treatment update.
AB  - Thrombocytopenia that is associated with infection due to human immunodeficiency
      virus (HIV) is an important and common hematologic abnormality. Although this
      condition is often asymptomatic, it may manifest clinically as a spectrum of
      bleeding problems including petechiae, ecchymoses, epistaxis, or menorrhagia or
      as hemorrhage of the gingivae, gastrointestinal tract, or CNS. Thrombocytopenia
      may be present in patients at any stage of immunodeficiency, and spontaneous
      remission can occur. We review the natural history of HIV-related
      thrombocytopenia and discuss treatment options.

PMID- 8562754
TI  - Chlamydia trachomatis seropositivity during pregnancy is associated with
      perinatal complications.
AB  - Sera from the mothers of all children from the greater Helsinki area who were
      treated in the Neonatal Intensive Care Unit (NICU) of Children's Hospital
      (University of Helsinki) during a 22-month period were studied serologically, and
      antibody levels for mothers were compared with those for matched controls. IgM to
      Chlamydia trachomatis serotype GFK was detected more often in sera from mothers
      with children in the NICU than in that from controls; IgM was detected in sera
      from 39 of 264 mothers vs. 15 of 274 controls (P < .001; two-tailed test). The
      gestational age of children born to mothers in the IgM-seropositive group was
      32.4 weeks whereas that of children born to mothers in the IgG/IgM-seronegative
      group was 34.3 weeks (all children were treated in the NICU). The frequency of
      signs of maternal infection (i.e., fever and vaginal discharge), the frequency of
      meconium-stained amniotic fluid, the frequency of chorioamnionitis, and the
      mortality rate were higher in the IgM-seropositive group than in the IgM
      seronegative group; pneumonia, atelectasis, and pneumothorax occurred more
      frequently in the seronegative group. Thus, in terms of birth weight and
      perinatal infections, the outcome was better for children whose mothers did not
      have antibodies to C. trachomatis.

PMID- 8562755
TI  - Usefulness of bone marrow examination in the evaluation of unexplained fevers in
      patients infected with human immunodeficiency virus.
AB  - The diagnostic usefulness of 69 bone marrow examinations (BMEs) performed for
      evaluating unexplained fever in 65 persons who were infected with human
      immunodeficiency virus was retrospectively compared with the usefulness of other
      diagnostic modalities used to investigate the cause of fever. An etiology for the
      fever was identified by BME in 22 of the 69 cases (diagnostic yield, 32%). In 19
      of these 22 cases, the same diagnosis had been made by another diagnostic
      modality, but the diagnosis was made by BME as rapidly or sooner in 10 of the 19
      cases and was made exclusively by BME in the three other cases. We suggest that
      BME is indicated when a diagnosis is urgently sought or when an evaluation with
      other diagnostic modalities has been unsuccessful.

PMID- 8562756
TI  - Juvenile dermatomyositis in a child infected with human parvovirus B19.
AB  - We report a case of juvenile dermatomyositis in which clinical onset occurred
      soon after infection with human parvovirus B19. To the best of our knowledge an
      association between juvenile dermatomyositis and human parvovirus B19 has not
      been previously reported. Parvovirus infection has been associated with several
      autoimmune diseases, and the findings in the case we describe raise the
      possibility that parvovirus may induce juvenile dermatomyositis, although we
      could not demonstrate a causal relationship.

PMID- 8562757
TI  - Sporotrichoid lymphangitis due to Staphylococcus aureus in a diabetic patient.
AB  - We describe a case of sporotrichoid lymphangitis (nodular lymphangitis or
      lymphocutaneous syndrome) that was an unusual clinical presentation of
      Staphylococcus aureus infection in a diabetic patient. Common pyogenic bacteria
      should be considered in the differential diagnosis of sporotrichoid lymphangitis.

PMID- 8562758
TI  - Delirium associated with acyclovir treatment in a patient with renal failure.
AB  - Neurotoxicity associated with acyclovir use is infrequently encountered. However,
      the half-life of acyclovir is greatly prolonged in patients with end-stage renal
      disease, predisposing these patients to neurological side effects that are
      generally reversible but occasionally severe. In general, renal dialysis
      effectively decreases the serum level of acyclovir, which correlates with
      toxicity. We report an unusual case of delirium and coma in a patient undergoing
      hemodialysis who was receiving what appeared to be an appropriately adjusted dose
      of acyclovir.

PMID- 8562759
TI  - Pseudomonas aeruginosa folliculitis due to non-O:11 serogroups: acquisition
      through use of contaminated synthetic sponges.
AB  - We describe the features of 13 cases of Pseudomonas aeruginosa folliculitis
      (eight of which occurred sporadically and five of which resulted from two family
      outbreaks) that developed subsequent to the use of commercial synthetic sponges
      for bathing. On the basis of O serogrouping and pyocin typing and subtyping, the
      strains recovered from the skin lesions were found to be identical to those
      isolated from household shower water and sponges. P. aeruginosa folliculitis is
      commonly caused by the serogroup O:11; The serogroups described in this study are
      rare causative agents of this type of skin infection. We believe that this is the
      first report of P. aeruginosa folliculitis due to serogroups O:3 and O:16.

PMID- 8562760
TI  - Candida albicans septic thrombosis of the right atrium is associated with a
      central venous catheter.
AB  - Right atrial thrombus formation is a rare complication of central venous
      catheterization in adults. Infection of this thrombus is exceptional. A case of a
      right atrial thrombus associated with Candida albicans infection is described.
      Surgical thrombectomy, withdrawal of the catheter, and long-term antiinfectious
      therapy seem the only appropriate treatment. The literature on this unusual
      condition is reviewed.

PMID- 8562761
TI  - Clinical course and treatment of adults with severe measles pneumonitis.

PMID- 8562762
TI  - Disk space infection due to Gardnerella vaginalis.

PMID- 8562763
TI  - Pasteurella pneumotropica pneumonia in a patient with AIDS.

PMID- 8562764
TI  - Treatment of Peptostreptococcus micros endocarditis with teicoplanin.

PMID- 8562765
TI  - Borreliosis as a cause of fever in a woman who recently returned from Saudi
      Arabia.

PMID- 8562766
TI  - Use of the Duke criteria for the diagnosis of infective endocarditis.

PMID- 8562767
TI  - Use of itraconazole for treatment of sporotrichosis involving a knee prosthesis.

PMID- 8562768
TI  - Primary human immunodeficiency virus infection presenting as myopericarditis and
      rhabdomyolysis.

PMID- 8562769
TI  - Toxoplasmosis of the bladder in a patient with AIDS.

PMID- 8562770
TI  - A case of anaerobic pericarditis.

PMID- 8562771
TI  - Antibiotic-associated pseudomembranous enteritis due to Clostridium difficile.

PMID- 8562772
TI  - Hallucinations associated with itraconazole therapy.

PMID- 8562773
TI  - Spinal cord compression due to anaerobic vertebral osteomyelitis in a patient
      with metastatic prostate cancer.

PMID- 8562774
TI  - Subdural empyema caused by Escherichia coli: hematogenous dissemination to a
      preexisting chronic subdural hematoma.

PMID- 8562775
TI  - Brain abscess due to Nocardia brasiliensis hematogenously spread from a pulmonary
      infection.

PMID- 8562776
TI  - Treatment of methicillin-resistant Staphylococcus aureus infection with
      quinupristin/dalfopristin.

PMID- 8562777
TI  - Preparation and use of fibrin glue in surgery.
AB  - Fibrin glue (FG) is used to control bleeding, to adhere tissues together, and to
      seal tissue defects. FG is prepared from platelet-rich plasma or by mixing
      concentrated fibrinogen solutions with thrombin. Concentrated fibrinogen
      solutions are produced by cryoprecipitation or by chemical precipitation of
      plasma. The literature on FG preparation is reviewed in order to compare the
      advantages and disadvantages of the different products reported and to summarize
      the clinical applications. It is concluded that additional studies are needed to
      fully evaluate the advantages and disadvantages of fibrinogen concentrated using
      cryoprecipitation and chemical precipitation and that specific advantages exist
      for use of both pooled homologous and autologous blood.

PMID- 8562778
TI  - Effects of a delayed steroid injection on ligament healing using a rabbit medial
      collateral ligament model.
AB  - Corticosteroids are known to inhibit collagen synthesis in vitro as well as
      having a deleterious effect on ligament healing when applied immediately
      following injury. An acute injection of betamethasone into a transected rabbit
      medial collateral ligament significantly impaired the biomechanical and
      histological properties compared to non-injected transected ligaments.
      Differences in mechanical, histological and biochemical properties were observed
      up to 3 months following injury and an acute steroid injection. The present study
      explored the effects of a corticosteroid (betamethasone) injection 7 days
      following the initial injury. Biomechanical and histomorphometric analyses were
      carried determine if the previously observed deleterious effects of a
      corticosteroid injection immediately following injury can be linked to an
      interference in the inflammatory phase of healing due to the presence of the
      corticosteroid.

PMID- 8562779
TI  - Effect of the tripeptide glycyl-L-histidyl-L-lysine on the proliferation and
      synthetic activity of chick embryo chondrocytes.
AB  - Under certain conditions chondrocytes form lattices with cartilage collagens,
      which may serve as cartilage implants. It is necessary to find the optimal
      conditions for culturing chondrocytes. Three different supports are compared: (a)
      plastic; (b) cartilage collagens; and (c) insoluble skin collagen solubilized
      under denaturing conditions (ISC-40). The effect of culture medium
      supplementation with the tripeptide (Gly-His-Lys)2.Cu.2H2O.2NaCl (GHK) on
      chondrocyte proliferation and synthetic activity is studied, with particular
      attention paid to collagen types I, II and III. The collagen supports stimulated
      chondrocyte proliferation, but on the ISC-40 support they started to
      dedifferentiate rather early. In the primary culture, chondrocytes on all three
      supports synthesized mainly collagen type II, and only small amounts of types I
      and III. In the first passage the synthesis of these two collagen types
      increased, relative to collagen type II, at least on the cartilage collagen
      support. Supplementation of culture medium with GHK stimulated chondrocyte
      proliferation in the primary structure mostly on the ISC-40 support. On the other
      two types of supports the stimulatory effect of GHK was expressed mostly in the
      first passages. The collagen synthetic rate was increased by GHK on both of the
      collagen supports; on the cartilage collagen support collagen type II was
      synthesized predominantly and on the ISC-40 support types I and III were mostly
      formed. It is suggested that supplementation of culture medium with GHK may be
      useful in the preparation of cartilage implants.

PMID- 8562780
TI  - Localized chronic suppurative bone infection as a sequel of peri-implantitis in a
      hydroxyapatite-coated dental implant.
AB  - Plaque-induced lesions can produce peri-implant bone loss with ultimate implant
      loss. Although the peri-implant tissues seem to be more resistant than the
      periodontal ones to plaque and calculus, they can produce a more extensive spread
      of the infection to the deeper tissues around implants. The case of a 45-year-old
      female patient is presented in which, over a three year period, there was a
      progressive loss of peri-implant bone and the formation of a periapical
      radiolucency with an external fistula. The implant was removed and examined with
      the cutting-grinding system. Microscopy examination showed that most of the
      hydroxyapatite (HA) was still adherent to the metal. There was a detachment in
      the area of the HA-titanium interface. The implant surface was almost completely
      covered by bacteria. Bacteria were also present in the bone medullary spaces
      surrounding the implant. The infection of the periodontal tissues had progressed
      into the alveolar bone, thus producing a localized bone infection. The cause of
      the implant failure is probably related to a defective connection of the abutment
      or to overloading of the implant due to the presence of interlocks in the
      prosthetic restoration.

PMID- 8562781
TI  - Influence of humidity on dimensional stability of a range of ion-leachable
      cements.
AB  - The dimensional changes of a variety of dental restorative materials, occurring
      during and after setting, were investigated. The materials were tested under four
      different environmental conditions: 25 degrees C at laboratory humidity, 25
      degrees C at 100% humidity, 37 degrees C at laboratory humidity and 37 degrees C
      at 100% humidity. Two materials setting by an acid-base reaction were also
      examined when protected with both a conventional varnish and a low-viscosity
      light-curable resin. The dimensional changes were recorded continuously using
      linear variable displacement transducers (LVDTs) over periods of up to 2 h. The
      materials investigated showed varying magnitudes of dimensional change. The
      shrinkage of conventional glass-ionomer cements (Fuji II and Opusfil) were the
      highest at 37 degrees C in air. This was attributed to the highest rate of water
      loss in the most desiccating environment. The shrinkage observed for the
      materials which set, even only in part, by a polymerization reaction will
      probably be due to the water loss and/or polymerization shrinkage. Exposure of
      these materials to a high-humidity environment reduced the shrinkage because of
      the swelling associated with water absorption. Application of the varnish and the
      protective resin over the cement surfaces also reduced shrinkage in Fuji II due
      to prevention of water exchange. The apparatus used in this study provided a
      simple and reliable method for measuring linear dimensional change. Data obtained
      in this study were comparable, where appropriate, to the values found in the
      literature.

PMID- 8562782
TI  - Low-temperature heat-deproteinated compact bone to heal large bone defects.
AB  - The potential of low-temperature (400 degrees C), heat-treated bone matrix in
      osteorepair has been evaluated in vivo by implantation into defects artificially
      created in rodent tibia. Histological and ultrastructural analysis of the bone-
      implant interface has been carried out on samples obtained at 1 to 6 weeks from
      operation. The obtained data showed that calcined bone is well tolerated and does
      not cause acute or chronic inflammatory reactions. Osteoid tissue, tightly
      adhered to the implant, appears within 2 weeks of the operation, while after 6
      weeks newly formed bone surrounds and infiltrates the implant. Of greater note,
      the detection of good adhesion between bone and implant ultrastructurally is
      demonstrated by the absence of fibrillar connective tissue at the interface. For
      these reasons, our preliminary observations suggest that low-temperature calcined
      bone (biological apatite or heat-deproteinated bone) may have a rightful place
      among the osteointegrators.

PMID- 8562783
TI  - Compressive and bone-bonding strength of hydroxyapatite thermal decomposition
      product implanted in the femur of rabbit as a bioactive ceramic bone cement.
AB  - Hydroxyapatite thermal decomposition product (HATDP) after mixing with water was
      injected into the femur of rabbits, and its biocompatibility, compressive
      strength and bone-bonding strength were investigated. The compressive strength of
      a block of HATDP was 56.0 MPa 4 weeks after injection, which was about 60% of
      that of poly(methyl methacrylate) (PMMA) cement. The bone-bonding strength was
      8.2 MPa 4 weeks after injection, which was significantly higher than that of PMMA
      cement. HATDP seems to be useful as a cement material because of its good bone
      bonding property and relatively high mechanical strength.

PMID- 8562784
TI  - Transmission electron microscopic observation of heterogeneous fluoridated
      hydroxyapatites.
AB  - Two different types of heterogeneous fluoridated hydroxyapatites previously
      synthesized at 80 degrees C and pH 7.4, which might be composed of hydroxyapatite
      covered with fluorapatite (H-FAp) and fluorapatite covered with hydroxyapatite (F
      HAp), were observed by high-resolution transmission electron microscopy. The
      transverse-sectional shapes of both apatites were clearly hexagonal. This
      confirmed that both apatites were highly crystallized. However, their shapes
      differed slightly from each other in detail:H-FAp was more slender and F-HAp was
      typically hexagonal, probably reflecting the shapes of the original core
      apatites, hydroxyapatite and fluorapatite. The portions thought to be synthesized
      with fluoride-free solution showed clear electron beam damage. The expanded
      lattice image observed at the edge of the F-HAp crystal coincided approximately
      with the a-axis dimension of 0.9443 nm obtained from the X-ray diffraction data
      of synthetic hydroxyapatite. After incubation in 0.5 mol l-1 acetate buffer
      solution (37 degrees C, pH 4.0) for one month, the fluorapatite-covered H-FAp
      maintained its sharp corners, while the hydroxyapatite-covered F-HAp showed
      rounded corners.

PMID- 8562785
TI  - Histological evaluation of polyesterimide-insulated gold wires in brain.
AB  - Polyesterimide-coated gold wires were implanted subdurally on the parietal cortex
      of rabbits for 16 weeks. Light microscope examination of the implant sites showed
      no evidence of toxicity. There was no inflammatory response of the adjacent
      parenchyma. Gliosis in the molecular or neuronal layers was only slight to
      moderate. Overall, the polymer demonstrated good biocompatibility at 16 weeks
      after implantation. Future, long-term biocompatibility studies of this material
      are indicated, including evaluation of tumourigenic properties.

PMID- 8562786
TI  - Assessment of a model for measuring drug diffusion through implant-generated
      fibrous capsule membranes.
AB  - Fibrous tissue, which encapsulates subcutaneously implanted silastic, vinyl,
      polyurethane and Teflon discs in rats, has been isolated, characterized and
      tested for drug permeability in order to develop an in vitro model for
      determining the effect of this tissue on drug disposition from implant sites.
      With all materials, capsule tissue thickness and collagen content (approximately
      59%) was consistent from 2 to 4 months after implantation. Silastic implants
      afforded the most consistent and usable tissue in terms of thickness and lack of
      vascularity, and these capsule membranes were used for determining the transport
      of three model compounds in an in vitro diffusion cell model. The rank ordering
      of permeability through these membranes was estrone (60.2 x 10(-6) cm s-1) > 3-O
      methylglucose (18.7 x 10(-6) cm s-1) > dextran of molecular weight 70 000 (5.6 x
      10(-6) cm s-1), which is consistent with expectations based on the molecular
      weights and partitioning behaviour of the model compounds. The results of these
      studies indicate that implant-generated encapsulating membranes can be
      successfully isolated and employed to study drug diffusion in an in vitro model,
      providing a direct assessment of the barrier properties of encapsulating
      membranes.

PMID- 8562787
TI  - Degradation of poly(lactic-co-glycolic acid) microspheres: effect of copolymer
      composition.
AB  - The in vitro degradation behaviour of a wide range of poly(D,L-lactic-co-glycolic
      acid) (PLGA) has been examined in terms of degree of degradation and
      morphological change during an incubation period of up to 53 d. Gel permeation
      chromatography and differential scanning calorimetry were employed to
      characterize their degradation profiles. It was found that amorphous PLGA
      exhibited a transient multiple crystallization behaviour of D- or L-lactic acid
      oligomers during degradation. This indicated that the hydrolytic scission of
      ester bonds tends to primarily target the linkage between glycolic acid and D- or
      L-lactic acid or glycolic acid. In addition, two distinctive glass transition
      temperatures appeared when these crystallization phenomena occurred, suggesting
      the transient presence of fast and slowly eroding polymer domains within
      microspheres during the degradation. This study supports the heterogeneous bulk
      degradation for PLGA microspheres which has been proposed recently for a large
      specimen.

PMID- 8562788
TI  - Carbodiimide cross-linked gelatin: a new coating for porous polyester arterial
      prostheses.
AB  - The performance of a polyester arterial prosthesis impregnated with gelatin and
      cross-linked with carbodiimide (Uni-graft) was compared with its porous parent
      graft (Protegraft) using a canine thoraco-abdominal bypass model. The grafts were
      investigated in terms of their handling characteristics, imperviousness at
      implantation, surface thrombogenicity and healing behaviour. Prostheses 30 cm in
      length were implanted for the following periods: 4, 24 and 48 h, 1, 2 and 4
      weeks, 2, 3, 4, 5 and 6 months. Both types of graft had good handling
      characteristics. The ready-to-use impregnated graft provided satisfactory
      haemostasis at implantation with no blood permeating through the wall after flow
      was restored. Both grafts exhibited low surface thrombogenicity, as determined by
      the uptake of labelled fibrin and platelets, and the healing sequence of the
      impregnated graft after resorption of the gelatin was equivalent to that of the
      preclotted control. Biodegradation of the gelatin was complete within 1 month of
      implantation with the subsequent development of a collagenous internal capsule at
      both anastomoses. Endothelial cells were observed between 4 and 6 months, but
      were confined to small islets distributed along the luminal surface. The
      prostacyclin/thromboxane A2 (PGI2/TXA2) ratio, which gives an indication of the
      level of endothelial cell activity, was greater than 1.0 after 1 week of
      implantation for the control graft. For the impregnated graft it reached 1.0 only
      after 3 months of implantation, but remained above 1.0 for periods of up to 6
      months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562789
TI  - Monocryl suture, a new ultra-pliable absorbable monofilament suture.
AB  - Synthetic absorbable sutures are available as braided constructions or as
      monofilaments. Braided absorbable sutures are made either from 90:10
      poly(glycolide-co-L(-)-lactide), sold by Ethicon, Inc. under the trade name
      Vicryl, or from polyglycolide, as sold, for instance, by Davis and Geck under the
      trade name Dexon. There are, however, some concerns with braided sutures that
      relate to tissue drag and the trauma this may cause, as well as the possible
      potentiation of infection through the interstices of the braid structure.
      Absorbable monofilaments, such as the monofilament sutures derived from p
      dioxanone homopolymer (PDS II, an Ethicon, Inc. product), or a copolymer of
      trimethylene carbonate and glycolide (Maxon, a Davis and Geck product), eliminate
      many of these concerns, but generally monofilaments do not handle as well as
      braids. This paper describes the research leading to the introduction of Monocryl
      (poliglecaprone 25) monofilament sutures, based on segmented block copolymers of
      epsilon-caprolactone and glycolide. Monocryl sutures will be shown to display
      excellent handling properties, minimal resistance during passage through tissue
      and excellent tensile properties. These sutures provide an in vivo breaking
      strength retention of approximately 20-30% after 2 weeks, considered by many to
      be the critical wound healing period. Absorption data on these sutures are
      presented; absorption is complete between the 91st and 119th days of
      implantation, with slight or minimal tissue reaction.

PMID- 8562790
TI  - Mapping of endogenous lectins in macrophages colonizing an implanted polymer
      surface--effect of polymer structure.
AB  - The design of synthetic polymers may affect structural features of inflammatory
      cells, for example the expression of endogenous sugar receptor molecules like
      lectins in macrophages and foreign body giant multinucleate cells. This
      characteristic was studied histochemically by use of biotinylated
      (neo)glycoproteins. The results demonstrate the influence of polymer structure on
      the phenotypic expression of molecules recognizing carbohydrates in these cells.
      Very strong activity was observed for carrier-immobilized beta-galactose in cells
      colonizing hydrophobic polystyrene implants. Sialic acid moieties were not
      recognized by cells located on the surface of all types of polymeric implant.
      This study encourages investigation of the influence of polymer design on the
      differentiation of macrophages.

PMID- 8562791
TI  - Comparison of covalently and physically cross-linked polyethylene glycol-based
      hydrogels for the prevention of postoperative adhesions in a rat model.
AB  - A covalently and a physicochemically cross-linked hydrogel, both based primarily
      on polyethylene glycol and both formed in situ, were compared side by side in a
      rat uterine horn devascularization and serosal injury model for efficacy in
      adhesion prevention. The primary difference between the two materials was the
      nature of their cross-linking. The covalently cross-linked hydrogel was a
      photopolymerized polyethylene glycol-co-lactic acid diacrylate, and the
      physically cross-linked hydrogel was a polyethylene glycol-co-polypropylene
      glycol, Poloxamer 407. In the surgical model employed, application of the
      covalently cross-linked hydrogel reduced the extent of adhesion formation from 75
      +/- 10% in the control group to 16 +/- 6% (mean +/- s.d., P < 0.001). Application
      of the physically cross-linked hydrogel reduced adhesion formation to 38 +/- 19%
      (P < 0.01). Retention of the two hydrogels upon the site of application was also
      evaluated. The covalently cross-linked hydrogel formed a continuous barrier upon
      the uterine horns for more than 4 d, while the physicochemically cross-linked
      hydrogel was present upon the uterine horns for less than 2 d. This difference in
      retention was probably the cause of the difference in efficacy and may be
      attributed to the nature of the cross-linking.

PMID- 8562792
TI  - Encapsulation of urease enzyme in xanthan-alginate spheres.
AB  - Urease-containing xanthan-alginate spheres were prepared by a two-step process
      which involved the Ca2+ coupling of the polysaccharides, followed by gentle
      glutaraldehyde cross-linking with amine groups of gelatin present in the initial
      mixture. This second step caused a slight decrease in the enzymatic activity but
      increased the stability. The water content and size distribution of the spheres
      were examined together with the sphere morphology. The effect of polymer ratio
      and enzyme loading on urease activity was investigated. An increase in xanthan
      content was found to affect the water uptake of the spheres. Temperature and pH
      stability of encapsulated urease was found to be higher than the free form. The
      xanthan-alginate spheres showed 75% of maximum urease activity even after 20
      repeated uses under optimal conditions.

PMID- 8562793
TI  - Effect of substituted dextran derivative on complement activation in vivo.
AB  - A soluble dextran derivatized with carboxylic groups (73%) and benzylamide
      sulphonate groups (15%), termed CMDBS 25, exhibited significant anticomplementary
      activity in the absence of anticoagulant activity. The polysaccharide inhibited
      both classical and alternative pathway-dependent complement activation in human
      and rat serum in vitro. Simultaneous administration of CMDBS 25 (100 mg) and
      crushed Sephadex G25 (20 mg) into normal Lewis rats suppressed systematic
      complement consumption that was induced by Sephadex in the animals by 98% for 1
      h. Two consecutive injections of 100 mg of CMDBS at 1 h interval resulted in
      total suppression of systemic complement activation for 2 h and in 50%
      suppression for an additional 2 h. Infusion of CMDBS alone was well tolerated and
      had no effect on CH50 in serum in vivo. Our results demonstrate that CMDBS 25
      exhibits anticomplementary properties in vivo and suggest that the polymer
      represents a potential therapeutic agent for pathological conditions associated
      with complement activation.

PMID- 8562795
TI  - Microscopic evaluation of bone-implant contact between hydroxyapatite, bioactive
      glass and tricalcium phosphate implanted in sheep diaphyseal defects.
AB  - In order to compare morphological discrepancies in bone-implant contact in
      vertebrates, cylinders of hydroxyapatite, bioactive glass and tricalcium
      phosphate were implanted in segmental defects of the tibia in sheep. Three types
      of visible bone-implant contact were observed microscopically at 4 months after
      implantation. The trabecular web-like bone-implant contact noted in tricalcium
      phosphate seemed superior to the disseminated patchy bone-implant contact in
      bioactive glass and the buttressed bone-implant contact in hydroxyapatite with
      respect to both bone ingrowth and bioresorption of the implant. Differences of
      physicochemical properties on the surface among the three kinds of bioceramic
      implants probably give rise to different types of bone-implant contact.

PMID- 8562794
TI  - Fabrication and characterization of dipalmitoylphosphatidylcholine-attracting
      elastomeric material for joint replacements.
AB  - Wear debris associated with the polyethylene components of total joint
      replacements has been shown to induce bone resorption which contributes to
      implant loosening. In an effort to promote lubrication and reduce wear in
      artificial hip joints, the use of the cushion bearing concept has been proposed
      previously; however, an elastomeric material tested as a cushion bearing has been
      shown to have poor tribological properties during initiation of motion from rest.
      The goal of this project was to fabricate and characterize an elastomer that has
      the ability to attract to its surface naturally occurring boundary lubricants
      from an aqueous solution. The test elastomer and appropriate controls were
      characterized using fluorescence, electron spin resonance and X-ray photoelectron
      spectroscopy. The test elastomer was found to have an enhanced ability to attract
      dipalmitoylphosphatidylcholine, a known physiological boundary lubricant. A
      cushion bearing that also encourages boundary lubrication represents a potential
      improvement over currently existing orthopaedic implant-bearing materials.

PMID- 8562796
TI  - Comparative study of the osteoinductive properties of bioceramic, coral and
      processed bone graft substitutes.
AB  - This study compared the osteoinductive properties of six different bone graft
      substitutes: Pyrost, natural coral, Callopat, Surgibone, demineralized Surgibone
      and demineralized rat bone. The materials were implanted heterotopically, in the
      abdominal musculature of rats, and the results evaluated histologically at 3 and
      6 wk post-implantation. Surprisingly, the results showed that both the
      demineralized rat bone and demineralized Surgibone were less osteoinductive than
      might be believed from the literature. Mineralized grafts showed no sign of new
      bone formation and exhibited variable resorption patterns. A layer of what
      appeared as dense calcification was seen around the coral implant. The most
      intense inflammatory reactions were exhibited with the xenografts Surgibone and
      demineralized Surgibone, indicating persistent immune responses. Coral and Pyrost
      elicited no marked inflammatory response, and this was attributed to the
      negligible amounts of protein present in these materials.

PMID- 8562797
TI  - In vitro effects of bone cements on the cell cycle of osteoblast-like cells.
AB  - The effects of orthopaedic cements on the proliferation and cell cycle of in
      vitro cultured MG63 osteoblast-like cells were examined. Five different cements
      were mixed and extracted at different time intervals (15 and 60 min, 6, 24 and 48
      h). Cell proliferation inhibition (CPI) was evaluated after 72 h culture as the
      toxicity parameter. As for the toxicity degree, the extracts were considered to
      have 'high toxicity' (CPI > or = 50%), 'medium toxicity' (50% > CPI > 25%), 'low
      toxicity' (CPI < or = 25%) and 'no toxicity' (CPI = 0). Cell cycle phases of MG63
      cells were evaluated at 24, 48 and 72 h by flow cytometry; the DNA content was
      assessed using the propidium iodide uptake and the percentage of cells in the S
      phase was determined using 5'-bromodeoxyuridine uptake. According to our results,
      the toxicity is inversely correlated with the time interval between
      polymerization and extract preparation, and is different according to the cement
      type. For some cements the effects are still observed 48 h after polymerization.
      The damaging effect is not linked to a specific phase of the cell cycle, nor does
      it hamper the restarting of cell proliferation at 72 h.

PMID- 8562798
TI  - Influence of dimensional stability of impression materials on the probability of
      acceptance of a prosthetic restoration.
AB  - The accuracy of rubber impression materials was evaluated by taking impressions
      of a steel model, pouring it with stone and comparing certain measurements
      between steel and stone models. It is assumed that acceptance is achieved when
      the difference in measurements is within permissible limits, defined by clinical
      criteria. A mathematical formulation of these criteria will lead to the concept
      of probability of acceptance. The probability is affected when the limits are
      changed. The particular case of satisfying two acceptance criteria that contain
      variables which are not statistically independent is considered, leading to the
      application of the bivariate normal distribution in the evaluation of acceptance
      probability.

PMID- 8562799
TI  - [Staying healthy at work--chances and risks in the daily routine of nursing].
AB  - They assist others to be healthy. On the other hand overwork, burnout and
      emotional disturbance are discussed more often within this particular
      occupational group than in any other professional fields. What makes nursing
      staff so vulnerable? What are the risks of care? What are the chances of making
      the work process of care healthy? How can we help the nursing staff to grow old
      in their own profession? This text is looking for answers to these questions. The
      author focuses on three topics: Nursing care as a female occupation, results of
      international research in the field of special demands in the working situation
      of nurses and organisational resources of nursing care to promote health at the
      work places of nursing personnel.

PMID- 8562800
TI  - [Electronic data processing in nursing: specific needs related to rostering
      programs in nursing].
AB  - Electronic data processing is taking over in the nursing domain in German
      hospitals. This is due, not only to the fact that computer hard- and software are
      getting better and cheaper, but also due to the legal demands of the new health
      legislation. Neither nurse-managers nor the nurses themselves are adequately
      prepared for this technical innovation or its implications. The dominant
      influence of management-interests leads to the danger that criteria relevant to
      the content of nursing fail to be taken into account. Consequently the quality of
      care may suffer. The Ministry for environment, energy, youth, family and health
      has commissioned the Agnes Karll Institute for Nursing Research to identify
      software features specific for the requirement of nurses. The study focuses on
      rostering programs for nursing staff allocation, in relation to the workload and
      on conditions which have to be met to make software nurse-friendly. Selected,
      important results are reported.

PMID- 8562801
TI  - [Head nurse and nursing expert--it is possible to achieve successful
      cooperation].
AB  - The employment of clinical nurse specialists (CNS) raises many questions. Often
      the collaboration of head nurse and CNS is described as a critical point. The
      authors work together in these positions successfully on the medical department
      of a university hospital. It is shown how the CNS's new position was created,
      what her everyday tasks look like and how the cooperation is organised. This
      collaboration is then evaluated. From the example, general conclusions are drawn,
      which--in the view of the authors--would be helpful in organising a successful
      collaboration of head nurse and CNS.

PMID- 8562802
TI  - [When women care for women].
AB  - What are the experiences of young nurses when they care for older women? The
      paper which follows is a shortened version of the dissertation presented at the
      conclusion of the diploma course for Clinical Nurse Specialists. I tried to
      answer the question: How do young nurses feel about nursing older patients? A
      qualitative method was chosen. Results show on the one hand, which older women
      fascinate young nurses, on the other hand, what they find lacking in the nursing
      care of older women. Care of these patients is very demanding. Recommendations
      are offered for the support of young professional women.

PMID- 8562803
TI  - [Moral action in nursing].
AB  - What ought I to do? is the classic question of moral dilemmas. It is concerned
      with the field of action in which human beings meet and where moral decisions
      have to be made in the course of everyday nursing care. Only when nurses discuss
      their own actual experiences, can they learn to arrive at a competent appropriate
      rationale and justification for action. With growing self-confidence, the
      willingness to act increases. Ethics is one of the relevant fields of knowledge.
      The attempt to create a link between moral action in nursing and ethics, comes to
      grief when the "myth of life and death" and the "Hypocratic myth" move centre
      stage. These myths really belong to the medical, not nursing perspective. Several
      other medical tendencies for generalisation and some in nursing, create barriers
      to the development of appropriate models for nursing action. It would be bad
      advice for nursing to present itself as a reservoir of humanitarianism. An appeal
      to professional conscience is no guarantee that morally defensible decisions will
      be arrived at. Only continuous examination of their own actions against a
      framework of sound moral argument can make it more likely that action appropriate
      to the desired goal can take place.

PMID- 8562804
TI  - [Quality assurance in nursing at a county hospital].
AB  - This paper describes the different stages of the implementation of a quality
      assurance programme in a teaching hospital (828 beds) in Switzerland. In this
      project, quality assurance is part of our concept of nursing care. The described
      stages represent the three first steps of the adapted model of quality assurance
      by Lang (1976): --Identification of values in nursing teams --Establishment of
      standards including criteria for structure, process and outcome --Quality
      measurement (Self-review and peer review) The following actions are considered
      important for a successful quality assurance programme: --decentralized procedure
      (bottom-up approach) --quality assurance by professional colleagues from within
      the hospital --peer reviewed quality assurance Although the nurses find the
      establishment of standards very difficult and need expert advice for this
      difficult task, the initiated programme can be considered successful.

PMID- 8562805
TI  - [Truth in dealing with sick people].
AB  - One of the most difficult problems for many nurses and physicians is the question
      of truthful information, especially for seriously ill and dying people. Talking
      about the problem of truth from an ethical point of view there are three
      essential aspects to consider: First the concept of truth from an anthropological
      point of view has to be defined and compared to the truth in the natural
      sciences, second, how the concept of "Truth at the sick bed" and its effect on
      nurses are treated in the medical literature, third, the psychological conditions
      we have to consider in relating to seriously ill and dying people. It is the
      declared aim of this paper to describe and summarize these three theoretical
      aspects, which in everyday work are inseparably connected, and to show some
      possible solutions.

PMID- 8562806
TI  - [Nursing science and sociology: in what way can sociological expertise support
      nursing research?].
AB  - Nursing science is currently orientated towards theories and methods from the
      social sciences. The article asks in which exact fields nursing science can use
      experiences of sociologists. Central topics are methodological aspects as well as
      concrete research contents. The following aspects are dealt with in greater
      detail: In the methodological field the relation of theory and practice is
      analyzed. Secondly, the relation of empirical and theoretical methods is
      described. Concerning the concrete research contents it is suggested that the
      topics nursing and society, nursing and hospital organisation, and the patient
      nurse-interaction by sociological means should be analyzed. Several examples
      relevant to nursing illustrate the argument.

PMID- 8562807
TI  - [Competence in nursing and its significance for professionalization].
AB  - The occupation of nursing is in an advanced stage of change. Demands for autonomy
      are manifest in the attempt to make nursing scientific. This results in raising
      the question, among others, of defining what it is about competence which makes
      it possible to call nursing a profession. Looking at developmental models, at the
      theory of socialisation one finds, typical of professions, congruence of head,
      heart and hand (cognitive, moral-communicative and pragmatic competence). An
      attempt is made to demonstrate that moral competence has the most important place
      because justice and caring form the nucleus of nursing models, within a framework
      of advocatorial ethics. Nursing loses its purpose if it is dominated by rationale
      of outcome and by the pragmatism of routine action. Professionalisation of
      nursing can make progress if research can provide valid arguments for autonomy,
      based on the competence paradigm described here.

PMID- 8562808
TI  - Calcium channels in vascular smooth muscle cells.
AB  - Control of intracellular Ca2+ ([Ca2+]i) is critical to vascular smooth muscle
      function. Calcium channels are the major route by which Ca2+ enters the smooth
      muscle cell. This article reviews the types of calcium channel present in
      vascular smooth muscle cells and their physiological and biochemical regulation.

PMID- 8562809
TI  - Fluoroprobe quantification of viable and non-viable cells in human coronary and
      internal thoracic arteries sampled at autopsy.
AB  - Viable and non-viable cells in coronary and internal thoracic arteries, collected
      at autopsy 7-24 h post-mortem from individuals 15-81 years of age, were detected
      using the fixable fluoroprobes 5-chloromethylfluorescein diacetate (green) and
      ethidium homodimer-1 (orange/red). Viability status of individual endothelial and
      smooth muscle cells was confirmed by simultaneous autoradiographic detection of
      incorporated [3H]glucosamine. Twenty-five percent of coronary and 42% of internal
      thoracic arteries contained viable cells up to 24 h following death. For the
      majority of viable vessels the mean percentage of viable cells ranged between 60
      and 80% with no significant difference between coronary and internal thoracic
      arteries and no relationship with either age of the donor or with time to
      autopsy. Non-viable cells were usually distributed fairly evenly amongst viable
      cells but this pattern could not be assumed. In a number of vessels non-viable
      cells were variably clustered in different regions of vessel wall. These findings
      confirm that vessels sampled at autopsy can be used for metabolic studies with
      the caveat that assessment of cell viability is a necessary prerequisite for
      interpretation of results.

PMID- 8562810
TI  - Distribution and peptide content of sympathetic axons innervating different
      regions of the cutaneous venous bed in the pinna of the guinea pig ear.
AB  - This study utilised catecholamine fluorescence histochemistry, multiple-labelling
      immunohistochemistry and retrograde axonal transport to determine the
      distribution and neuropeptide content of sympathetic neurons innervating veins in
      the dorsal skin of the guinea pig pinna. There was a dense plexus of sympathetic
      axons innervating the large central vein at the base of the ear and the adjoining
      maxillary vein. The density of the plexus decreased towards the distal margin of
      the ear and in smaller veins, and was very sparse in the lateral veins at the
      base of the ear. Small venules < 50-80 microns diameter were not innervated.
      Probably all noradrenergic axons in the large veins near the base of the ear
      contained immunoreactivity (IR) to neuropeptide Y (NPY), but the proportion of
      axons with NPY-IR decreased in large veins in more lateral regions of the ear,
      and in smaller veins (80-100 microns diameter). Injections of Fast Blue or DiI
      close to large veins in the ear resulted in retrograde labelling of tyrosine
      hydroxylase-IR neurons in the ipsilateral superior cervical ganglion, 64% of
      which contained NPY-IR. Nearly all (> 90%) of the TH-IR axons in small and large
      veins also contained IR to dynorphin-related peptides. Thus, sympathetic
      venoconstriction in the thermoregulatory bed of the guinea pig pinna is likely to
      occur predominantly in the large central veins towards the base of the ear.
      Furthermore, sympathetic constriction is likely to be qualitatively different in
      large cutaneous veins from that occurring in small veins, and absent altogether
      from small venules and some lateral veins.

PMID- 8562811
TI  - Role of nitric oxide and potassium channels in the cholinergic relaxation of
      rabbit ear and femoral arteries: effects of cooling.
AB  - The main objective of this work was to study the role of potassium channels in
      the cholinergic relaxation of cutaneous arteries during cooling. Acetylcholine
      (10(-8)-10(-4) M) produced isometric concentration-dependent relaxation of
      precontracted segments of rabbit ear (cutaneous) and femoral (noncutaneous)
      arteries; this relaxation was higher at 24 degrees C (cooling) than at 37 degrees
      C in ear, but not in femoral, arteries. In both types of arteries, at 37 and 24
      degrees C, the relaxation to acetylcholine was partially reduced by the inhibitor
      of nitric oxide synthase NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), and
      the relaxation that remained after L-NAME was higher at 24 degrees C than at 37
      degrees C in ear, but not in femoral, arteries. At 37 and 24 degrees C, the
      persistent relaxation to acetylcholine after L-NAME was further reduced by smooth
      muscle depolarization with medium containing a high concentration of potassium (6
      x 10(-2) M), and with the nonspecific inhibitors of potassium channels
      tetraethylammonium (10(-2) M) or 4-aminopyridine (5 x 10(-3) M) in both ear and
      femoral arteries. In ear arteries, the inhibitor of high conductance calcium
      activated potassium channels charybdotoxin (10(-7) M), alone or combined with L
      NAME, reduced the relaxation to acetylcholine at 24 degrees C, but not at 37
      degrees C. In femoral arteries, charybdotoxin alone did not modify, but combined
      with L-NAME reduced, the relaxation to acetylcholine at either temperature. At 37
      and 24 degrees C, the inhibitor of low conductance calcium-activated potassium
      channels apamin (10(-7) M), the inhibitor of ATP-dependent potassium channels
      glibenclamide (10(-5) M) and the cyclooxygenase inhibitor meclofenamate (10(-5)
      M), alone or combined with L-NAME, did not modify the relaxation of both ear and
      femoral arteries to acetylcholine. These results suggest: (1) the cholinergic
      relaxation of cutaneous (ear) and noncutaneous (femoral) arteries could be
      mediated by endothelial nitric oxide and by activation of potassium channels, and
      (2) cooling increases the relaxation of cutaneous arteries to cholinergic
      stimulation, which may be mediated, in part, by an increased response of
      potassium channels.

PMID- 8562812
TI  - Effect of age and sex on residual stress in the aorta.
AB  - When ring segments of artery free of external loads are cut longitudinally, they
      spring open. This property which has been termed residual strain, is a
      manifestation of an underlying residual stress and may be quantified by measuring
      the degree to which the cut ring springs open. Residual stress serves to
      redistribute the forces in the media and to minimize the stress gradient between
      its inner and outer margins. Its magnitude and distribution are closely related
      to vascular growth and development. We have measured the degree of opening (in
      terms of an opening angle, see below for its definition) in 168 rings removed
      from six positions along aortae obtained at autopsy from 30 subjects aged between
      3 months and 87 years. At all ages, there was an overall increase in opening
      angle along the aorta away from the heart. At all positions, the opening angle
      increased with age and was higher in vessels with visible atheroma. At all ages,
      the opening angle was significantly greater in males than in females. This
      difference persisted when allowance was made for the greater incidence of
      atheroma in males. We have found a similar age-related increase in rats, although
      there was no difference between males and females. These observations are
      consistent with a recently proposed 'stress-growth' law in which remodelling of
      the arterial wall is driven by the non-uniform distribution of stress across it
      and may be associated with known sex-related differences in the aetiology of
      cardiovascular disease.

PMID- 8562813
TI  - High potassium diets reduce macrophage adherence to the vascular wall in stroke
      prone spontaneously hypertensive rats.
AB  - Our previous study demonstrated that high potassium (K) diets reduce stroke
      mortality in stroke-prone spontaneously hypertensive rats (SHRsp) even when the
      blood pressure is not lowered. On the other hand, macrophage infiltration into
      the vascular wall is known to play an important role in the development of
      arterial lesions. In this study, in vivo and in vitro experiments were performed
      to examine the effect of high K diets on macrophage adherence to the vascular
      wall in SHRsp rats. In the in vivo study, 51Cr-labelled macrophages, collected
      from the peritoneal cavity, were injected intravenously to SHRsp rats fed 6% high
      NaCl diets containing either normal 0.5% K or high 2.1% K, and, 45 min later, the
      rats were perfused with buffered saline to remove blood. Radioactivity from
      macrophages in the aorta was 40% lower in the high K SHRsp than in the normal K
      SHRsp (p < 0.002), and the brain of high K SHRsp also showed a 52% lower
      macrophage radioactivity than that of normal K SHRsp (p < 0.007). Although the
      mean blood pressure was slightly lower in the high K diet group than in the
      normal K diet group (167 vs. 184 mm Hg), these differences remained still
      prominent even when we compared groups with matching blood pressures; -33% for
      the aorta (p < 0.02) and -55% for the brain (p < 0.02). In the in vitro study,
      the aortas of SHRsp rats similarly fed on normal or high K diet were excised and
      mounted in a perfusion chamber. They were perfused with labelled macrophages at
      normotensive or hypertensive pressure. In normal K SHRsp, macrophage
      radioactivity remained in the washed aorta was 158% higher in high perfusion
      pressure group than in normal pressure (p < 0.002). However, they did not
      significantly differ between two perfusion pressures in high K SHRsp. These
      results indicate that high K diets reduce endothelial injuries which allow
      adherence and infiltration of macrophages into the vascular wall of hypertensive
      animals, and thereby contribute to the reduction of vascular lesions and stroke
      mortality.

PMID- 8562815
TI  - [Scientific aspects of the organization of congresses. The scientific committee].

PMID- 8562814
TI  - Intraluminal flow preferentially increases net sodium uptake in the rabbit facial
      vein.
AB  - The infusion of physiological salt solution into the lumen of ring segments of
      the isolated rabbit facial vein induces an increase in vessel wall tone. Changes
      in 22Na+ and 45Ca2+ net uptake as well as 22Na+ unidirectional efflux in response
      to flow in this vessel were compared to the response to histamine (1 microM) and
      to angiotensin II (0.1 microM). 22Na+ net uptake per unit force developed in
      response to flow was 7.9-fold greater than that for histamine (1 microM) and
      twice that for angiotensin II (0.1 microM). In comparison, 45Ca2+ net uptake per
      unit force in response to flow, histamine and K+ were similar. Flow-induced
      contraction and the related 45Ca2+ and 22Na+ net uptake were decreased by
      amiloride (30 microM) and methyl isobutyl amiloride (30 microM) without changes
      in 45Ca2+ or 22Na+ net uptake per unit force. Ouabain (10 microM) enhanced flow
      induced contraction and the related 22Na+ net uptake. Both ouabain (10 microM)
      and Bay K 8644 (1 microM) increased flow-induced contraction and the related
      45Ca2+ net uptake whereas they decreased the 45Ca2+ net uptake per unit force.
      Flow, histamine and angiotensin II increased the unidirectional efflux of 22Na+.
      This increase in 22Na+ unidirectional efflux was attenuated by ouabain (10
      microM). These experiments demonstrate that the increases in wall force due to
      flow, histamine and angiotensin II are associated with increases in 22Na+ net
      uptake and unidirectional efflux. Flow preferentially promotes the entry of Na+,
      compared to histamine and angiotensin II.

PMID- 8562816
TI  - [Role of the social worker in the primary care team: let's plan a dream].

PMID- 8562817
TI  - [Nephropathy and microalbuminuria in type II diabetes].
AB  - OBJECTIVE: To study the population receiving care to find the prevalence of
      diabetic Nephropathy (DNP) and its association with possible risk factors in type
      2 Diabetes Mellitus. DESIGN: A descriptive crossover study. SETTING: An urban
      health district with an aged and socio-economically depressed population.
      PATIENTS: Randomised sampling among the health district's registered diabetics (n
      = 198). MEASUREMENTS AND MAIN RESULTS: Among other parameters, the values of
      Proteinuria and Microalbuminuria in 24 hour's urine and of serum Creatinine were
      analysed. On the basis of these values the four stages of DNP were established:
      I) Normality, II) Microalbuminuria, III) Proteinuria, IV) Renal failure. The
      prevalences recorded were 33.8%, 51%, 11.1% and 4%, respectively. Also studied
      was the value of Microalbuminuria measured at random by reactive strips dipped in
      urine, which displayed 78% sensitivity and 68% specificity. The most notable of
      the DNP risk factors were how long the DM had evolved (p = 0.005). Age (p =
      0.02), the value of the glucosilated haemoglobin (p = 0.03) and of the
      triglycerides (p = 0.03) were also related factors. On analysing the association
      of DNP with other chronic complications of DM, a statistical relationship to the
      presence of Retinopathy (p < 0.001) and peripheric Vasculopathy (p < 0.001) was
      observed. CONCLUSIONS: The presence of some stage of DNP among the type 2 DM
      population is very common. Only 33.8% of the sample was normal regarding the
      urinary excretion of proteins. Microalbuminuria quantified at random with
      reactive strips has low specificity. The highest risk factor for DNP is the
      length of the DM's evolution, with age and metabolic control of the disease also
      being important.

PMID- 8562818
TI  - [Analysis of repeat prescriptions in chronic treatments at a health center].
AB  - OBJECTIVES: To describe the social-health profile of the population attending for
      the renewal of prescriptions for long-term treatments; to quantify the possible
      pharmacological interactions; to measure cognitive function in a sample of this
      population. DESIGN: Crossover study. SETTING: Urban Health Centre. PARTICIPANTS:
      All the patients (359) who were seen during a one month period at any of the
      centre's nursing stations for the renewal of long-term treatment prescriptions.
      MEASUREMENTS AND RESULTS: All the social-health data of every patient were
      collected on a form. Cognitive function was assessed in one of every three cases
      by means of Folstein's Minimental test. Average age was 64 +/- 0.76; 37% were men
      and 63% women. The mean number of chronic diagnoses per patient was 3.2 +/- 0.08
      and of medicines per patient 2.9 +/- 0.09. 15% medicated themselves.
      Pharmacological interactions were possible in 41% of the patients who took more
      than one medicine. 8% were illiterate and 16% only knew how to read or write.
      24.54% displayed overall cognitive deterioration and 48%, lapses in memory.
      CONCLUSIONS: Patients seen at our Centre for renewal of prescriptions were an
      elderly population group, with pluripathology, taking several medicines, with a
      low cultural level and deterioration in their cognitive functions. The risk of
      pharmacological interactions is very high. Repeat prescriptions for long-term
      treatments should not just be an administrative function: it should be performed
      by trained health staff.

PMID- 8562819
TI  - [Diabetes and ignored disorders of glucose tolerance in primary care. Evidence
      from opportunistic detection. Group for the Study of Diabetes in Tarragona].
AB  - OBJECTIVE: To investigate the level of attendance for care of people with glucose
      tolerance disorders, both known and not, and to discuss their real impact on
      Primary Care. DESIGN: Simple prospective randomised sampling. Opportunist
      detection among spontaneous users over 40, excluding pregnant women. SETTING:
      Primary Health Care. PATIENTS AND OTHER PARTICIPANTS: Data was recorded using a
      pre-designed survey, which included the recognised Diabetes (DM) risk factors.
      MEASUREMENTS AND MAIN RESULTS: Of the 183 cases evaluated, DM was already known
      in 13 (7.1%). 15 (8.2%) with unknown DM and 27 (14.7%) with GIT. A strong link
      was demonstrated with the average age and a marked tendency to overweight and
      obesity only significant when comparing DM with the rest. As to the risk factors
      researched, there was a significant association with antecedents of prior
      tolerance abnormality, DM in pregnancy, hyperglucaemiant medicines and ischaemic
      disease, in cases where family antecedents of definite diabetes were not found.
      CONCLUSIONS: The frequency of attendance of users with diabetes and unknown
      glucose tolerance disorders is very high in spontaneous primary care
      consultations. These results suggest that opportunist detection should be
      encouraged in primary health care centres.

PMID- 8562820
TI  - [Delegated prescription by specialists in primary care].
AB  - OBJECTIVES: To describe the qualitative-quantitative features of Primary Care
      prescriptions originated by specialists. DESIGN: A crossover descriptive study.
      SETTING: Txantrea Health Centre (Pamplona). PATIENTS AND OTHER PARTICIPANTS: All
      the prescriptions originated by out-clinic or hospital specialists over a two
      month period, in three Health Centre clinics. MEASUREMENTS AND MAIN RESULTS: The
      number of prescriptions passed on to Primary Care was 3,009, costing 5,303,071
      pesetas, which was 31.61% of the drugs prescribed and 38.08% of the
      pharmaceutical expenditure of the three clinics during the period under study.
      65.88% of the prescriptions corresponded to out-clinic specialists and 34.11% to
      hospital specialists. They were not accompanied by a clinical note, the treatment
      and the length of treatment in 33.46%, 36.55% and 45.39% of cases, respectively.
      The group and sub-group with most prescriptions passed on were Cardiovascular
      Apparatus and Calcium antagonists. The commonest active principal was
      acetylsalicylic acid. 79.89% were taken orally, 88.20% were single drugs and
      73.28% of the medicines had high intrinsic value. CONCLUSIONS: An important
      proportion of Primary Care's pharmaceutical expenditure was identified as
      originating with specialists. There was scant information given for following up
      the patients. Improvement of communication between different care levels on the
      basis of common procedures and objectives would be a useful step towards better
      quality of care.

PMID- 8562821
TI  - [Evolution of pharmaceutical provision in the National Health System (1984
      1994)].
AB  - OBJECTIVES: To analyse the free pharmaceutical provision of the National Health
      Service, using the customary indicators. DESIGN: Longitudinal, retrospective and
      observational study, embracing the years 1984 to 1994. SETTING: The provision,
      using official National Health Service prescriptions, of pharmaceutical products
      via dispensaries. PARTICIPANTS: Prescriptions of the period under study.
      MEASUREMENTS AND MAIN RESULTS: The measurements for the evolutionary analysis of
      free pharmaceutical provision were carried out in absolute and relative values.
      Within the absolutes, public health expenditure on drugs went from 178,348
      million pesetas in 1984 to 643,701 million in 1994; and prescriptions from 432
      million in 1984 to 494 million in 1994. Beneficiaries' contributions for drugs,
      as a percentage of overall consumption, went down from 15.75% in 1984 to 9.16% in
      1994. The indicators of pharmaceutical prescription placed the cost of sale to
      the public per prescription in 1994 at 1,446 pesetas, an increase of 195% over
      1984, whereas the average expenditure per prescription (1,303 pesetas in 1994)
      went up by 215%. Expenditure per protected pensioner went from 18,180 pesetas in
      1984 to 56,784 in 1994, with an average number of prescriptions per pensioner of
      38.04. In this last year the tendency for consumption to fall, begun in 1993. The
      profiles of the therapeutical sub-groups, which were most consumed in cost terms,
      displayed large variations. CONCLUSIONS: The structural management measures
      adopted during the period under study, especially those for 1993 (new VAT on
      drugs, Royal Decree on Selective Financing of Medicines) and 1994 (average fall
      of 3% in the free sale price of drugs, collaboration of Dispensaries) are, in our
      view, those which have most affected the evolution of this free provision.

PMID- 8562822
TI  - [Prenatal biopsychosocial risk and preeclampsia].
AB  - OBJECTIVE: To evaluate the clinical presentation of arterial hypertension induced
      by pregnancy and pre-eclampsia (AHPP) in patients exposed to prenatal
      biopsychosocial risk (PBPSR). DESIGN: A prospective double-blind study. SETTING:
      Primary Care. Four Health centres in Mendoza (Argentina), Cali and Popayan
      (Colombia) and Tegucicalpa (Honduras). PATIENTS: 1,076 pregnant women who were
      monitored from week 14 to 28 of pregnancy without there having been clinical
      evidence of pathology at the start. MEASUREMENTS AND MAIN RESULTS: 97 (9.9%) of
      the 1,076 pregnant women interviewed were withdrawn from the study because their
      records were incomplete or they had received therapy for psychosocial risk.
      Average age of the 979 pregnant women studied was 26.2 +/- 5.8. 339 (34.6%) were
      first carriers, 439 (44.9%) had a low social-economic level, 268 (27.3%) were
      exposed to high biopsychosocial risk and 69 (6.4%) developed AHPP. An evaluation
      of the patients with this condition found that 52 of these (75.3%) were exposed
      to high PBPSR [RR = 8.5, C.I. 95%, 4.5-15.9, p < 0.001], 22 (42.3%) displayed
      anxiety and/or poor family support during their pregnancy; and 30 (57.7%) were
      exposed only to biomedical risk factors [RR = 3.07, C.I. 95%, 1.96-4.82, p <
      0.001]. CONCLUSIONS: Whenever, as part of the evaluation of prenatal risk, the
      biopsychosocial risk is evaluated, the possibility of identifying pregnant
      patients who will develop AHPP doubles.

PMID- 8562823
TI  - [Family counseling in primary health care: a systemic approach].

PMID- 8562824
TI  - [Interpretation of negative results in research in health sciences].

PMID- 8562825
TI  - [Arterial hypertension and left ventricular hypertrophy].

PMID- 8562826
TI  - [Inhaled terbutaline and muscular symptoms].

PMID- 8562827
TI  - [The future of gatekeeping in Spain].

PMID- 8562828
TI  - [Oral anticoagulation from the primary care perspective].

PMID- 8562829
TI  - [Control of anticoagulation in primary care].

PMID- 8562830
TI  - [Home management of hyperosmolar decompensation induced by furosemide].

PMID- 8562831
TI  - [Something less about adverse reactions to medications].

PMID- 8562832
TI  - Vascular endothelial cell activation and permeability responses to thrombin.
AB  - The serine protease, thrombin, evokes numerous endothelial cell responses which
      regulate hemostasis, thrombosis and vessel wall pathophysiology. One such
      response, the development of intercellular gap formation and vascular
      permeability is relevant to each of these processes and is a cardinal features of
      inflammation. Regulation of endothelial cell gap formation and therefore
      permeability is a function of a dynamic balance between competing adhesive,
      barrier-promoting tethering forces and contractile, tension-producing forces
      which result in barrier dysfunction. The key tethering events governing focal
      endothelial cell adhesion to the extracellular matrix and cell-cell interactions
      are poorly understood. In contrast, information is rapidly increasing regarding
      endothelial-specific contractile processes driven by the actomyosin molecular
      motor. The level of myosin light chain phosphorylation catalyzed by a unique
      myosin light chain kinase promotes productive actin-myosin interaction and
      governs the degree of centripetal tension produced. In this review the signal
      transducing and contractile mechanisms by which thrombin elicits endothelial
      cellular activation through its specific receptor are addressed. The pathways by
      which thrombin may alter the balance between contractile and tethering forces to
      promote endothelial cell gap formation are discussed.

PMID- 8562833
TI  - Hemostatic abnormalities in patients with pulmonary embolism compared with that
      in deep vein thrombosis.
AB  - We investigated hemostatic abnormalities in 37 patients with deep vein thrombosis
      (DVT) and pulmonary embolism (PE) (PE patients) and in 40 patients with DVT
      without PE (DVT patients). Plasma fibrinogen, thrombin-antithrombin complex
      (TAT), plasmin-plasmin inhibitor complex, fibrin-D-dimer, activated protein C
      (APC)-protein C inhibitor (PCI) complex, von Willebrand factor (vWf), tissue
      plasminogen activator (t-PA), PA inhibitor-I (PAI-1), and thrombomodulin levels
      in both PE and DVT patients were significantly increased compared with normal
      volunteers. Plasma APC-PCI complex, PAI-1, and vWf levels in PE patients were
      significantly higher than those in DVT patients without PE. These findings
      indicate that PE patients are more hypercoagulable and hypofibrinolytic than DVT
      patients. Plasma TAT, APC-PCI complex, PAI-1, and vWf levels were the most
      sensitive indicators for PE. In these patients, increases in TAT and APC-PCI
      complex suggest DVT and increased PAI-1 and vWf suggest the risk of onset of PE.

PMID- 8562834
TI  - Structural domains of thrombin involved in the induction of mitogenesis in
      cultured human vascular smooth muscle cells.
AB  - Human alpha-thrombin is a known human vascular smooth muscle cell (HVSMC)
      mitogen. We have previously reported that gamma-thrombin, in which the anion
      binding exosite is disrupted, but not catalytically inactivated PPACK-thrombin is
      mitogenic on HVSMC. Here, the structural requirements for thrombin's mitogenic
      activity on HVSMC were further investigated. Total inhibition of thrombin-induced
      DNA synthesis was achieved by AT-III and hirudin. AT-III, added 1 h after
      exposure of cells to thrombin, failed to alter thrombin-induced mitogenicity.
      Modification of thrombin's anion binding exosite with peptides derived from the C
      terminal sequence of hirudin resulted in a partial loss of thrombin's mitogenic
      activity. PPACK-inactivated thrombin failed to induce a significant expression of
      the immediate early gene, c-fos. Unlike PPACK-inactivated thrombin, alpha
      thrombin and gamma-thrombin induced a significant increase in the level of the
      PDGF-A gene expression. A correlation between PDGF-A gene induction and thrombin
      induced mitogenicity was suggested by the fact that the mitogenic forms of
      thrombin also stimulated PDGF-A gene expression. Together, these results indicate
      that the mitogenic activity of thrombin on HVSMC requires the integrity of the
      enzyme's active site and is altered by modifications of its anion binding
      exosite.

PMID- 8562835
TI  - Selective activation of heparin cofactor II by a sulfated polysaccharide isolated
      from the leaves of Artemisia princeps.
AB  - While checking anticoagulant activities in crude fractions from Wakan-Yakus
      (traditional herbal drugs), we detected antithrombin activity in the
      polysaccharide fraction of the leaves of Artemisia princeps Pamp. A sulfated
      polysaccharide purified from the crude fractions by ion-exchange chromatography
      on DEAE-cellulose and gel filtration on Sepharose 6B potentiated the heparin
      cofactor II (HC II)-dependent antithrombin activity but not the antithrombin
      activity of antithrombin III (AT III). The polysaccharide enhanced the HC II
      thrombin reaction more than 6000-fold. The apparent second-order rate constant of
      thrombin inhibition by HC II increased from 3.8 x 10(4) (in the absence of the
      polysaccharide) to 2.5 x 10(8) M-1 min-1 in the presence of 25-125 micrograms/ml
      of the polysaccharide. In human plasma, the polysaccharide accelerated the
      formation of thrombin-HC II complex. The stimulating effect on HC II-dependent
      antithrombin activity was almost totally abolished by treatment with
      chondroitinase AC I, heparinase or heparitinase, while chondroitinase ABC or
      chondroitinase AC II had little or no effect. These results suggest that the
      polysaccharide is a glycosaminoglycan-like material with properties that are
      quite distinct from heparin or dermatan sulfate.

PMID- 8562836
TI  - The role of von Willebrand factor in haemostasis and blood loss during and after
      cardiopulmonary bypass surgery.
AB  - Excessive perioperative and postoperative bleeding continue to complicate
      cardiopulmonary bypass surgery (CPB). In this study we measured the von
      Willebrand factor antigen (vWF:Ag), collagen binding assay (CBA) and ristocetin
      cofactor assay (RiCo) in 52 patients undergoing CPB. The collagen binding assay
      employs the affinity of the high-molecular-weight multimers of vWF to collagen
      and was used in this study to demonstrate differences in the multimeric
      composition of vWF during and after CPB. The observed values for the vWF:Ag, CBA
      and RiCo were correlated to the amount of postoperative bleeding. Both the
      preoperative vWF:Ag and the CBA showed significant negative correlation with
      postoperative blood loss (r = -0.3046, P < 0.05 and r = -0.3228, P < 0.05
      respectively). Higher blood loss figures correlated with lower vWF:Ag, CBA and
      RiCo during and after surgery with the strongest correlation 1 h post-op between
      both vWF:Ag and CBA and actual blood loss (r = -0.5061, P < 0.001 and r = 
      0.4942, P < 0.001 respectively). The strong negative correlations between vWF:Ag,
      CBA and RiCo before, during and after CPB and blood loss data verify the
      important role of vWF in primary haemostasis. Of particular note, the negative
      correlations between preoperative levels of vWF:Ag, CBA and postoperative blood
      loss provide valuable insight into another possible mechanism of excessive
      bleeding post CPB.

PMID- 8562837
TI  - Functional analysis of an unusual length polymorphism in the human antithrombin
      III (AT3) gene promoter.
AB  - The prevalence of the alternative alleles of an unusual length polymorphism in
      the promoter of the human antithrombin III (AT3) gene was determined in a sample
      of 155 unrelated individuals from the Northern Irish population. The 108bp L
      allele and the 32bp S allele occurred at frequencies of 0.21 and 0.79
      respectively. Some homology was noted between the L-specific sequence and the
      region immediately downstream. Residual homology was also evident between the L
      and S sequences, suggesting that the S allele was derived from the L allele
      during evolution by partial deletion followed by sequence divergence. The
      functional significance of the polymorphism was investigated by transient
      transfection of AT3 promoter/luciferase reporter gene constructs into two human
      hepatoma cell lines in vitro. The promoter strength of the L allele was found to
      be 1.6-fold higher than the S allele in HepG2 cells whereas in Hep3B cells, the
      strength of the S allele was 1.7-fold higher than that of the L allele. In order
      to evaluate the phenotypic consequences of the AT3 promoter polymorphism in vivo,
      plasma samples from the 155 control individuals were assayed for antithrombin III
      (ATIII) activity. Mean activities of the different promoter polymorphism
      genotypes (SS, LL, SL) were not significantly different. These results suggest
      that the AT3 promoter polymorphism does not contribute to the variation in plasma
      ATIII activity that occurs in the general population.

PMID- 8562838
TI  - Markers of coagulation activation for evaluation of the antithrombotic efficacy
      of heparin: a prospective study in acute deep venous thrombosis.
AB  - The potential value of measurements of prothrombin fragment 1 + 2 (F1 + 2),
      thrombin-antithrombin complexes (TAT) and D-dimer for the assessment of
      antithrombotic efficacy of heparin in acute deep venous thrombosis (DVT) was
      prospectively investigated. These variables were determined at presentation and
      subsequently once daily during a course of seven days heparin therapy. Heparin
      doses were adjusted according to the activated partial thromboplastin time
      (APTT). Compression ultrasonography was performed at presentation and on day 7 to
      determine the extent of thrombosis according to a predefined score. Out of a
      total of 50 patients accrued to the study 44 patients had reduced or unchanged
      extent of thrombosis, whereas in six patients an extension was documented.
      Although thrombin generation was significantly inhibited after initiation of
      heparin therapy as reflected by a decrease in F1 + 2 and TAT levels, these
      markers were not useful for the detection of patients with DVT extension. In
      contrast, anti-factor-Xa activities but not APTT measurements were significantly
      lower in the group of patients with propagation of DVT (median: 0.22 U/ml versus
      0.38 U/ml, interquartile range: 0.1-0.33 U/ml versus 0.19-0.55 U/ml; P = 0.001).
      D-dimer decreased within the first days of heparin therapy but failed to indicate
      DVT progression. These data suggest that plasma anti-factor-Xa activity
      correlates better with the antithrombotic efficacy of heparin than APTT
      measurements and markers of coagulation or fibrinolysis activation.

PMID- 8562839
TI  - Thrombocytopenia, antithrombin deficiency and extensive thromboembolism in
      pregnancy: treatment with low-molecular-weight heparin.
AB  - Pregnancy limits the therapeutic options for managing thrombocytopenia which
      occurs in 5% of patients on heparin. We describe a case of extensive
      thromboembolism associated with antithrombin (AT) deficiency complicated by
      thrombocytopenia which resolved when low-molecular-weight heparin was instituted.
      A primigravid woman presented at 11 weeks gestation with bilateral femoral
      occlusive thrombi extending above the renal veins. Investigations revealed AT
      deficiency, thrombocytopenia and renal infarction. After low-molecular-weight
      heparin was substituted for unfractionated heparin, the thrombocytopenia resolved
      and although the pregnancy was lost, the patient made a full recovery.

PMID- 8562840
TI  - Heterozygous factor VII deficiency and severe hemophilia A in the same kindred.
AB  - The association between heterozygous factor VII deficiency and severe hemophilia
      A in the same family is described. The 18-year-old proposita had a negative
      personal history for bleeding events and underwent clotting evaluation after a
      fortuitous finding of a prolonged PT. Decreased levels of both factor VII
      activity and antigen to about 50% of normal, compatible with heterozygous
      deficiency, were found in her and in three other asymptomatic siblings. Two
      uncles on the paternal side had severe hemophilia A and also showed low factor
      VII levels. However, in these two patients factor VII deficiency was secondary to
      chronic liver disease due to hepatitis B and C virus infections. Combined
      clotting defects in the same kindred may be due to an independent segregation of
      two separate defects or to common gene(s) malfunction. Factor VII deficiency is
      frequent and probably underestimated in the general population. For these reasons
      factor VII deficiency can easily segregate with other clotting defects.

PMID- 8562841
TI  - Presentation of an acquired factor VIII inhibitor with a muscular haematoma
      mimicking a deep venous thrombosis in a patient with breast cancer.
AB  - Acquired haemophilia is a rare disorder that it is associated with several
      diseases. Patients may present with spontaneous haematomas in different places
      which can sometimes be fatal. We present a 69-year-old woman with breast
      carcinoma who developed a factor VIII inhibitor. The initial haemorrhagic event
      was a spontaneous deep muscular haematoma in the right leg mimicking a deep
      venous thrombosis. She was successfully treated with prednisone.

PMID- 8562842
TI  - Influence of protein C resistance (APC-R) on the determination of proteins C and
      S by functional clotting assays.

PMID- 8562843
TI  - Suppression of F1+2 (thrombin) generation in patients with DVT requires increased
      doses of heparin.

PMID- 8562844
TI  - Prevalence of parvovirus B19 infection in Portugal.

PMID- 8562845
TI  - Studies of protective properties of pluronic and other agents on the hybridoma
      cell culture.
AB  - The potential toxicity and optimal concentrations of different protective agents
      such as pluronic F-68, methylcellulose (MC), CMC, and GPE on the in vitro growth
      of murine hybridoma 2F7 cells that secrete monoclonal antibody against small-cell
      lung cancer were studied. The effect on the rate of glucose utilization of adding
      protective agents was investigated. The protective effects of different
      concentrations of the protective agents at high agitation speed were also
      observed. It showed that 0.05% to 0.10% (w/v) of pluronic F-68 and 0.10% to 0.20%
      (w/v) of MC could protect hybridoma cells from shear stress at high agitation
      speed. Adding pluronic F-68 could increase glucose utilization rate, but
      increased the ammonia production rate. Although CMC did not affect 2F7 cell
      growth at a concentration less than 0.10% (w/v), it exhibited no protective
      property. GPE could lyze hybridoma cells. In a 1.5-L CelliGen bioreactor, when
      the pluronic F-68 concentration was 0.10% (w/v) in the medium and agitation speed
      was 70 r/min, the hybridoma cells could grow normally.

PMID- 8562846
TI  - High-level expression of human beta-interferon gene in the silkworm with new
      constructed BmNPV vector.
AB  - Bombyx mori nuclear polyhedrosis virus (BmNPV) and Bombyx mori cells as well as
      silkworm larvae were used successfully for the production of biologically active
      recombinant proteins. There are only a few types of BmNPV general vectors. Here a
      new type of vector plasmid pBm92 was constructed in this experiment. The
      translational initiation codon ATG of the polyhedrin gene in Pbm92 was changed
      into ATT, and then five cloning sites of a foreign gene were ligated after the
      +12 bp site of the polyhedrin gene. Human beta-interferon (HuIFN-beta) gene was
      cloned into Pbm92 to construct pBmIFN +12; meanwhile we constructed the transfer
      vector Pbmifn-3 in which HuIFN-beta was cloned after the -3 bp site of the
      polyhedrin gene. BM-N cells were cotransfected with the two types of transfer
      vector plasmid DNAs and BmNPV genomic DNA. Recombinant viruses that were screened
      did not produce polyhedrin inclusion bodies in the virus plaque assay, and were
      identified by the hybridization of recombinant virus DNA with HuIFN-b gene probe.
      IFN activity of the culture media of Bm-N cells infected with recombinant virus
      BmIFN +12 was 2.0 x 10(6) IU/mL, and IFN activity of hemolymph of silkworm larvae
      infected with BmIFN +12 was 5.0 x 10(7) IU/mL. Expression level of BmIFN +12 was
      two to four times more than that of BmIFN -3. The rHuIFN-beta produced by BM-N
      cells and silkworm larvae has an antigenicity identical to that of the native
      HuIFN-beta.

PMID- 8562847
TI  - cDNA cloning and sequencing of 54kDa fragment of the 75kDa readthrough protein
      gene from beet necrotic yellow vein virus.
AB  - With viral RNA extracted from purified beet necrotic yellow vein virus (BNYVV)
      isolated from Inner Mongolia, the first strand of cDNA encoding a 54kDa fragment
      of the 75kDa readthrough protein on the RNA2 was synthesized by reverse
      transcription. A double-strand cDNA fragment of 1.5 kb was obtained after 30
      cycles of PCR amplification. The fragment was ligated into and mapped on pGEM
      7Zf(+). The result of sequence analysis shows that the 54kDa readthrough domain
      is 1509 nucleotides (nt). Compared with F13 isolate, the fragment shares 94.97%
      identity in terms of nucleotides with 3 nt deletion and 96.42% identity of
      deduced amino acids.

PMID- 8562848
TI  - A study of growth kinetics of the flocs from Schizosaccharomyces pombe.
AB  - Inducing yeast cells to self-flocculate could be considered a cell immobilization
      method. The growth kinetics of the flocs from Schizosaccharomyces pombe was
      studied in an experimental suspended-bed bioreactor with starch hydrolysate
      obtained by two-stage enzymatic hydrolysis. It was discovered that a limited
      oxygen supply was necessary during continuous ethanol fermentation with yeast
      flocs. The oxygen supplied was a kind of limited substrate effecting on the floc
      growth. Further, a kinetic model describing this floc growth was proposed.

PMID- 8562849
TI  - Molecular cloning, sequencing, and expression in Escherichia coli of the chalcone
      synthase gene.
AB  - Flavonoids form a class of secondary metabolites that are abundant in all higher
      plants. They serve important functions in flower pigmentation. Chalcone Synthase
      (CHS) is a key enzyme in the biosynthesis of all classes of flavonoids;
      therefore, variation of the expression of CHS might change the color of flowers.
      We cloned CHS-A gene from Petunia hybrida, which has 99% sequence homology with
      those that have been cloned abroad. The sequence of the coding region is 1170bp
      and encodes a protein of 39kDa. CHS-A gene is also expressed high-efficiently in
      E. coli. All this work establishes a sound basis for future research on the
      impact of the CHS-A gene on flower pigmentation.

PMID- 8562850
TI  - Crown gall culture and production of tanshinone in Salvia miltiorrhiza.
AB  - Crown galls were induced by direct infection of sterile seedlings with
      Agrobacterium tumefaciens C58, and the transformation was proved by opine
      identification. The crown galls grew well in a hormone-free medium. B5 and MS
      basic media were good for the growth of crown galls (strain Ca), which increased
      up to 102 and 90 times in a month, respectively. However, 67-V and WP basic media
      are good for tanshinone production. It has been shown that crown galls can be
      utilized as a culture system to produce secondary metabolites.

PMID- 8562851
TI  - Effects of biological factors on cell growth and anthocyanin formation by
      suspended cultures of Perilla frutescens cells.
AB  - Effects of biological factors (i.e., size of cell aggregates, subculture period,
      and inoculum density) on cell growth and production of anthocyanin pigment (a
      secondary metabolite) by suspended cultures of Perilla frutescens plant cells
      were investigated on a flask scale. It was found that anthocyanin content was
      lower in a culture inoculated with cells of size greater than 250 microns,
      compared with unscreen-sized cells or cells smaller than 250 microns. Subculture
      periods of 7 and 10 days were suitable for the cell cultures since favorable
      growth and a high level of anthocyanin content were maintained during a long
      period of subculture. An inoculum density (wet cells) of 50 g/L was the best for
      both the cell growth and pigment accumulation in flask culture of P. frutescens
      cells.

PMID- 8562852
TI  - A secretion expression system using promoter and signal peptide of cholera toxin
      B subunit gene.
AB  - A secretion expression plasmid vector pMC05S was constructed taking advantage of
      the promoter, signal peptide, and transcriptional terminator of cholera toxin B
      subunit gene and beta-galactosidase was overexpressed in E. coli and most of the
      expressed enzyme was secreted into periplasma when the lacZ gene was inserted
      downstream of the signal peptide sequence of pMC05S. The yield of beta
      galactosidase by engineered E. coli reached 30 mg/L and most of the beta
      galactosidase retained the activity of the enzyme. The appropriate host strain
      and medium were also investigated. This system provided a new approach for the
      expression of proteins that easily form inclusion bodies.

PMID- 8562853
TI  - The regulation of pac gene expression by CRP and FNR.
AB  - The expression of pac gene is under the regulation of many factors. The
      mechanisms of glucose and oxygen regulation have been studied. It was found that
      FNR showed no effect on the expression of pac, and CRP activated the expression
      of pac. The possible binding site of CRP was found to be located upstream to the
      pac promoter.

PMID- 8562854
TI  - Studies on selection and characterization of a stress-tolerant sugarcane cell
      line.
AB  - A sugarcane (Saccharum sinensis Roxb.) cell line R932 resistant to growth
      inhibition by the proline analogue hydroxyproline was selected. R932 showed
      greater tolerance to PEG and low temperature stress than the donor. The line R932
      showed larger accumulation of proline (x3.2) than the sensitive donor. In vitro
      enzymic analysis of gamma-glutamyl kinase involved in the proline biosynthesis
      showed that the enzyme in the R932 was less sensitive to inhibition by 50-mM
      exogenous proline than that in the donor. The results suggested that the change
      in gamma-glutamyl kinase properties might lead to excessive accumulation of
      proline, and the elevated proline contents might in turn lead to an increase in
      tolerance to environmental stress.

PMID- 8562855
TI  - Hormones and/or growth factors in prostate hypertrophy, pathophysiology and
      treatment.

PMID- 8562856
TI  - Finasteride: a clinical review.
AB  - Finasteride is the first of a new class of 5 alpha-reductase inhibitors which
      allows selective androgen deprivation affecting dihydrotestosterone (DHT) levels
      in target organs such as the prostate and scalp hair without effecting
      circulating levels of testosterone thus preserving the desired androgen mediated
      effects on muscle strength, bone density and sexual function. Finasteride has
      been demonstrated to produce significant effects in men with an enlarged prostate
      gland. The long-term data now emerging suggests that progression of benign
      prostatic hyperplasia (BPH) may be arrested providing additional long term
      benefits. Experimental uses in prostate cancer prevention and male pattern
      baldness offer new and exciting possibilities for this class of compounds.

PMID- 8562857
TI  - Gn-RH agonists in the treatment of prostatic carcinoma.
AB  - About 80% of advanced prostate cancers are hormone dependent. Androgen withdrawal
      by either surgical castration or medical castration is the first-line treatment
      for this disease. As the patient's choice and quality of life are now being taken
      into account, reversible medical castration with GnRH analogues has emerged as a
      new palliative treatment. The use of these compounds alone or in combination with
      anti-androgens and the timing of initiating the hormone therapy were reviewed.
      Unfortunately, relapses after androgen ablation occur in most patients, as their
      cancer becomes insensitive to androgens. Management of hormonal refractory cancer
      remains a challenge to clinicians. No clinical trial using promising new
      therapeutic approaches such as GnRH antagonists, GnRH analogues linked to
      cytotoxic radicals, or a combination of GnRH analogues with somatostatin
      analogues or bombesin/GRP antagonists have been published until now.

PMID- 8562858
TI  - Current treatment of BPH.
AB  - Benign prostatic hypertrophy (BPH) is one of the most common diseases of adult
      males which increases with age. Effective therapeutic agents are an attractive
      option for patients for whom surgery is not a necessity, improving quality of
      life when compared with watchful waiting. Epidemiological studies show that 88%
      of patients over 80 years of age present anatomical BPH. This prevalence is
      similar in male populations throughout the world. Surgical treatment
      (transurethral resection of the prostate: TURP) has been the gold standard for
      over 50 years in patients with an enlarged prostate and obstructive symptoms but
      20% of patients remain unsatisfied with surgery. Various medicinal preparations
      have been used since biblical times, in particular plant extracts which are still
      prescribed in Europe. Some claim to have an enzymatic inhibitory effect, but
      currently have not demonstrated objective efficacy. Alpha-blockers act on bladder
      and prostate smooth muscle, the contraction of which is mediated through alpha 1
      receptors. Treatment has shown increased uroflow, decreased residual volume and a
      decrease in symptoms of BPH. Alpha-blockers; however, have shown no effect on
      prostate volume nor a reduction in the need for surgery for these patients.
      Finasteride, currently the only 5 alpha-reductase inhibitor approved for
      treatment of symptomatic BPH, has been widely investigated. The drug has been
      shown to decrease prostate volume, improve symptoms, uroflow and invasive
      urodynamic parameters in the majority of patients. Dihydrotestosterone (DHT) is
      decreased but the level of serum testosterone is maintained. Prostatic specific
      antigen is decreased by 50% as an effect of the drug on epithelial cells.
      Overall, the drug is well tolerated but some patients have shown decreased libido
      and/or impotency; however, two-thirds of these patients improved when the
      treatment was continued. Two effective medical therapies are currently available
      for treating symptomatic BPH: finasteride and alpha antagonists. Studies are now
      in progress to determine whether a combination of these therapies would be an
      effective alternative to surgery or watchful waiting.

PMID- 8562859
TI  - The so-called phyto-estrogenic action of Pygeum africanum extract.

PMID- 8562860
TI  - A Pygeum africanum extract with so-called phyto-estrogenic action markedly
      reduces the volume of true and large prostatic hypertrophy.

PMID- 8562861
TI  - Autoantibodies in hepatitis delta.
AB  - Hepatitis delta virus infection is associated with a wide range of different
      autoantibodies. The humoral immune response in chronic hepatitis D is directed
      against the cytoskeleton, the nucleus, the nuclear lamina and the endoplasmic
      reticulum. Smooth muscle antibodies (SMA), basal cell layer antibodies (BCLA),
      stellate epithelial cell antibodies (SECA), thymic reticular cell antibodies
      (TRA), perithymocytic cell antibodies (PTA), and anti-calmodulin antibodies are
      reactive with constituents of the cytoskeleton. Antinuclear antibodies (ANA) and
      anti-lamin C antibodies recognize antigens of the nucleus and the nuclear lamina,
      respectively. Autoantibodies directed against antigens of the endodoplasmic
      reticulum (LKM) are also common in chronic hepatitis D. Recently, the major
      molecular target of LKM-3 autoantibodies was described as an epitope on UDP
      glucuronosyltransferases of family 1. In view of the important role of UGTs in
      drug metabolism, LKM-3 autoantibodies represent a new model to study virus
      induced autoimmunity in man. Future studies should focus on the role of the host
      immune response and the clinical relevance of these autoantibodies in chronic
      hepatitis D.

PMID- 8562862
TI  - Tissue acylcarnitine and acyl-coenzyme A profiles in chronically hyperammonemic
      mice treated with sodium benzoate and supplementary L-carnitine.
AB  - The aim of the present study, was to establish the hepatic profile of acyl
      coenzyme A (acyl-CoA) in relation to the hepatic profile of acylcarnitines in
      chronically hyperammonemic spf mice (hereditary deficiency in ornithine
      transcarbamylase) treated with sodium benzoate alone or in combination with L
      carnitine. The muscular profile of the acylcarnitines and the stability of
      sarcolemma were also assessed in the same mice. Following administration of
      sodium benzoate, we observed decreases in hepatic total and free coenzyme A and
      in acetyl-CoA, which was accompanied by an increase in hepatic acyl-CoA. This
      treatment also resulted in increased free carnitine, decreased total carnitine,
      and decreased short and medium chain acylcarnitines in the liver. Increases in
      plasma creatine kinase levels, muscular free, total, and in short and medium
      chain acylcarnitines were also observed in this treatment group. In mice
      receiving a combination of sodium benzoate and L-carnitine, increases in free and
      total coenzyme A, acetyl-CoA and in free, total and esterified hepatic carnitines
      were observed. In this treatment group, the plasma level of creatine kinase was
      found to be reduced, while the free muscular carnitine was increased. Our results
      indicate that sodium benzoate is implicated in the decrease of total hepatic
      coenzyme A, through either an inhibition of CoA synthesis or activation of its
      degradation. The distribution of hepatic coenzyme-A and of hepatic and muscular
      carnitine (free or esterified) is altered following administration of sodium
      benzoate which results in a further destabilization of the sarcolemma induced by
      hyperammonemia. Supplemental treatment with L-carnitine was shown to have a
      positive effect by increasing hepatic coenzyme A and carnitine levels and
      restoring the stability of the sarcolemma caused by the treatment of sodium
      benzoate alone.

PMID- 8562863
TI  - The growth of human HIV-1 infected U937 cells in immune-deprived mice.
AB  - We report in vivo growth of human promonocytic cells infected with HIV-1
      presented in new mouse model. Cloned U937 cells chronically infected with HIV-1
      were grafted in (CBA*C57B1/6)F1 mice deprived of immunity by thymectomia and
      total body irradiation with subsequent marrow reconstitution. Nine weeks after
      cell inoculation, HIV-1-positive cells were found only in mice that received an
      additional single dose of cyclophosphamide (100 mg/kg bw) prior to
      transplantation, whereas, in mice without further immune deprivation, the
      complete elimination of cells bearing viral antigen occurred already on the
      seventh day after transplantation. The approach described may be suitable for in
      vivo development of antiviral drugs against latent infection in macrophage-like
      cells which represent a serious problem in therapy of AIDS in humans.

PMID- 8562864
TI  - Lipoprotein (a) and fibrinolytic system in liver cirrhosis. Coagulation
      Abnormalities in Liver Cirrhosis (CALC) Study Group.
AB  - Several observations have suggested that lipoprotein (a) (Lp(a)) is a risk factor
      for coronary artery disease because of potential interference with fibrinolysis
      secondary to its activation of plasminogen. However, there are few data on the
      possible role of Lp(a) in liver cirrhosis. The present study was carried out, to
      better elucidate its relationship to the fibrinolytic system in liver cirrhosis.
      We studied the plasma levels of Lp(a) and the fibrinolytic parameters of 95
      patients with liver cirrhosis (57 men, 38 women, aged 26-81). Patients in Child
      Pugh class C (n = 32) had significantly lower levels of Lp(a) than those in class
      B (n = 45), and the class B had lower Lp(a) values than class A (n = 18) (1.4
      (0.0-3.7) vs 2.9 (0.0-6.1) vs 3.4 (1.8-5.5); the data are log-transformed). Alpha
      2-antiplasmin and plasminogen, had patterns similar to those of Lp(a), tissue
      plasminogen activator (t-PA) was significantly increased only in class C (class
      A: 7.5 +/- 5.8 ng/ml; class B: 10.8 +/- 7.7 ng/ml; class C: 19.1 +/- 11.3 ng/ml).
      Patients with systemic hyperfibrinolysis (cross-linked fibrin degradation
      products, XDP > 200 ng/ml) also had lower levels of Lp(a) than those without 1.6
      (0.0-4.4) vs (0.0-6.1); p = 0.0002. There was a significant correlation between
      Lp(a) and plasminogen (r = 0.43; p = 0.001). Lipoprotein (a) progressively
      decreases as liver cirrhosis worsens but it appears unlikely to be involved in
      causing the hyperfibrinolytic state often observed in advanced liver cirrhosis,
      in which there are marked abnormalities of several other fibrinolytic parameters,
      also including increased t-PA and decreased inhibitors.

PMID- 8562865
TI  - Triggering effects of BCG vaccine on antitumor and interleukin-1 secretory
      activity of T cell lymphokine-primed macrophages.
AB  - By using an in vitro model, this work demonstrates that BCG (Bacillus Calmette
      Guerin) vaccine is able to trigger activation of T cell lymphokine-primed murine
      macrophages (Mo) for both tumoricidal cytotoxicity and interleukin-1 (IL-1)
      secretion. The results presented support the view that BCG vaccine may
      essentially activate primed, but not intact Mo; and that macrophage-mediated both
      antitumor and immunostimulatory effects of BCG vaccine observed in the body may
      be largely defined by functional activity of T-lymphocytes responsible for
      antigen-induced production of macrophage-activating lymphokines.

PMID- 8562867
TI  - Triazolines 31--anticonvulsant properties of three triazoline--and
      aziridinedicarboximide derivatives.

PMID- 8562866
TI  - Enkephalinase-blocking agent thiorphan affects cell growth and differentiation in
      long term culture of mouse bone marrow.
AB  - Enkephalinase-blocking agent thiorphan was added to long-term cultures of mouse
      bone marrow cells at the time of culture initiation (time 0) or 2 weeks
      thereafter, when the stromal layer appears. Cellularity, cell morphology (in
      cytospin smears) and the yield of granulocyte-macrophage progenitor cells (GM-CFC
      assay in agar) were recorded. Low concentrations of thiorphan accelerated
      recovery of the cultures after an initial drop of the cell count. Expansion and
      maturation of the granulocytic lineage was promoted, with parallel decline of the
      GM-CFC yield. Thiorphan probably interfered with the activity of enkephalinase
      (endopeptidase 24.11) in the cultures. That enzyme is the CD10 surface marker
      (CALLA) of lymphoid, myeloid and stromal elements.

PMID- 8562868
TI  - Membrane potential of rat hepatoma cells in culture: influence of factors
      affecting amino acid transport.
AB  - The effect has been studied of various media, hormones and of amino acids on the
      membrane potential of rat hepatoma cells in culture measured by microelectrode
      impalement. Cells in Eagle's minimal essential medium plus 5% serum had a value
      which varied daily from about 5-8 mV, inside negative. The membrane potential of
      rat hepatocytes was measured to be 8.7 +/- 0.2 mV, inside negative. The membrane
      potential of the hepatoma cells was decreased by insulin and increased by
      glucagon. Membrane potential was unaffected by change of medium to Hanks' or
      Earle's balanced salt solutions or deprivation of serum. It was, however, reduced
      in cells in phosphate-buffered saline and by reduction of pH. The former effect
      was shown to be due to the higher [Na+] of phosphate-buffered saline as opposed
      to the other media. Addition of alanine, glycine, serine, proline and
      methylaminoisobutyrate all reduced membrane potential by 2-3 mV. Smaller
      decreases were seen with methionine, leucine and phenylalanine, but none with
      glutamine, threonine, BCH (2-aminonorborane-2-carboxylic acid) and D-alanine. The
      results are compared with the effects of similar conditions on aminoisobutyrate
      uptake. Whilst there was a correlation under some conditions there was not under
      others. It is concluded that for the hepatoma cells factors additional to the
      membrane potential must exert some influence on the capacity for amino acid
      transport.

PMID- 8562869
TI  - Effects of L-alanine and L-alanine peptides on the chemotaxis of tetrahymena:
      evolutionary conclusions.
AB  - L-alanine and its peptides (L-Ala-2-6) do not attract or repulse Tetrahymena in a
      10(-8) M concentration. In 10(-10) M concentration there is a consistent
      repellent effect. Twenty four hours after L-alanine or L-alanine-peptides'
      pretreatment (imprinting) the progeny generation of the cells react differently
      to the same materials. L-Alanine, L-alanine penta- and hexapeptide in both
      concentrations are chemoattractant, while L-alanine tetrapeptide is repellent. L
      Alanine dipeptide is inert in 10(-10) M and repellent at 10(-8) M concentrations,
      while L-alanine tripeptide is strongly repellent at 10(-10) M and attractant at
      10(-8) M concentrations. This means, that the first encounter (imprinting) with
      an exogenous amino acid or peptide is decisive to the later reaction of the
      protozoan cell. The chain length is important in the imprinting, however the
      reaction is not consistent. The experiments call the attention to the
      significance of imprinting in the receptor and hormone evolution.

PMID- 8562870
TI  - Hexachlorocyclohexanes affect the arachidonic acid release from
      phosphatidylinositol but not from other phospholipid classes in tubular cell
      cultures.
AB  - Gamma- and delta-isomers of hexachlorocyclohexane caused marked decreases in the
      levels of radioactive phospholipids, and increases in the levels of
      [3H]arachidonate incorporated into free fatty acids in rat renal tubular cells.
      The increased radioactivity of free fatty acids arises from the decrease of
      [3H]arachidonate incorporated into phosphatidylinositol, but not into
      phosphatidylcholine, phosphatidylserine or phosphatidylethanolamine. This fact
      suggests that phosphatidylinositol can be broken down to the fatty acid from the
      sn-2 position and lysophospholipid by a phospholipase activity increased by
      hexachlorocyclohexanes. The observed specific toxicant action could be achieved
      in two ways: (a) operating upon a specific phospholipase A2 that acts on
      phosphatidylinositol, but not on other phospholipids as substrates and/or (b)
      involving substrate-phospholipase A2 interactions. Interestingly, the observed
      effect of the delta-isomer was more pronounced than that of the gamma-one.

PMID- 8562871
TI  - Changes in T-cell subpopulations in mice during prolonged experimental secondary
      infection with Echinococcus granulosus.
AB  - Balb/c mice were infected intraperitoneally with protoscoleces of Echinococcus
      granulosus. After 15 months of infection, and by means of flow cytometry, the
      expression of T-cell markers CD3, CD4, and CD8 on T cells from peripheral blood,
      spleen, and thymus was analyzed and compared with that of age-matched controls.
      Infected mice had higher percentages of CD3+, and CD4+ cells in peripheral blood,
      and higher percentages of CD8+ cells in the spleen, when compared with control
      mice. CD4+ and CD8+ cells in peripheral blood and CD8+ cells in thymus also
      showed higher percentages of expression of interleukin-2 receptor. The results
      infer a role for interleukin-2 in experimental secondary echinococcosis.

PMID- 8562872
TI  - The anticalmodulin effect of aflatoxin B1 on purified erythrocyte Ca(2+)-ATPase.
AB  - The genotoxic carcinogen aflatoxin B1 (AFB1) inhibited the calmodulin-stimulated
      membrane-bound (Ca2+Mg2+)-ATPase. Using the purified enzyme, 12 nmoles per ml of
      AFB1 caused maximum inhibition of 28% and 50%, of the acidic phospholipid
      stimulated and calmodulin-activated Ca(2+)-ATPase activity respectively.
      Treatment of red cell ghosts with increasing concentrations of Triton X-100, a
      non-ionic detergent caused a progressive loss of both the basal and calmodulin
      stimulated Ca(2+)-ATPase activity. The activity of the phospholipid-free,
      detergent-solubilized enzyme was almost fully restored by phosphatidyl serine
      (PS) and its sensitivity to calmodulin was restored in the presence of
      phosphatidyl choline (PC). Analysis of the results obtained using varying
      concentrations of ATP shows that AFB1 did not affect the Km and Vmax of the
      unstimulated enzyme whereas these parameters were reduced by about 75% and 50%,
      respectively, in the presence of calmodulin. Using the product of limited
      proteolysis by trypsin i.e. the 90 kDa fragment which still retains its
      calmodulin binding-domain and the 76 kDa fragment which has lost this domain,
      kinetic studies on the enzyme activity revealed that AFB1 inhibited the
      calmodulin-activated 90 kDa fragment by about 50% while the 76 kDa was not
      affected at all by the toxin and calmodulin. The toxin had no significant affect
      on the basal activity of the 90 kDa limited proteolysis fragment of the enzyme.
      These observations suggest that AFB1 inhibits the activated Ca(2+)-ATPase by
      binding to an important site in the calmodulin-binding domain of the enzyme. It
      seems likely that the toxin binds to tryptophan in the calmodulin-binding domain,
      thus causing a reduction in the rate at which this domain can interact with
      Ca(2+)-calmodulin or acidic phospholipids. The implication of these observations
      is that Ca(2+)-extrusion and other calmodulin-activated enzymes and processes may
      be slowed down during prolonged exposure to AFB1 because of its anticalmodulin
      effect.

PMID- 8562873
TI  - IR and turbidity studies of vitamin E-cholesterol-phospholipid membrane
      interactions.
AB  - Binary and tertiary mixture of alpha-tocophenol, cholesterol and
      dimyristoylphosphatidylcholine in the form of multilamellar liposomes were
      investigated by Fourier Transform Infrared and visible spectroscopy. Results of
      the FTIR and turbidity experiments indicate that alpha T decreases or diminishes
      the effect of cholesterol on the frequency and the bandwidth of the C-H
      stretching, CH2 scissoring and C = O stretching bands in FTIR spectra and the
      turbidity measurements (recorded as absorbance values at 440 nm) in phospholipid
      model membranes.

PMID- 8562874
TI  - Identification of a high affinity taurine transporter which is not dependent on
      chloride.
AB  - Taurine transport by lactating gerbil mammary tissue has been examined. Taurine
      uptake is mediated by a high-affinity system which is specific for beta-amino
      acids. The uptake of taurine is Na(+)-dependent but appears not to be obligatory
      dependent upon Cl-. Thus, replacing Na+ with choline almost abolished taurine
      uptake. Substituting Cl- with NO3- had no effect whereas SCN- induced a small but
      significant increase in taurine influx. Taurine uptake was Na(+)-dependent under
      conditions where Cl- had been replaced with NO3-. However, it is apparent that
      the Na(+)-dependent taurine transport system requires the presence of a permeable
      anion because replacing Cl- with gluconate markedly reduced taurine uptake. Cell
      swelling, induced by a hyposmotic challenge, increased the efflux of taurine from
      gerbil mammary tissue via a pathway sensitive to niflumic acid.

PMID- 8562875
TI  - Histochemical and immunohistochemical study on the skin of patients with
      ossification of the posterior longitudinal ligament in the cervical spine.
AB  - We present an immunohistochemical study on extracellular matrix (ECM), decorin,
      in the epidermis and dermis of patients with ossification of the posterior
      longitudinal ligament (OPLL) to clarify the abnormality in the extracellular
      matrix of the skin of OPLL. Localization of decorin and TGF-beta in the skin was
      studied. All patients with OPLL showed a diffuse strong staining of decorin in
      the entire epidermal layer. The epidermis was also positive for TGF-beta antibody
      staining. Patients with cervical spondylotic myelopathy showed weak or no
      staining of decorin. Abnormality in the regulating system of TGF-beta may be
      involved in the precipitation of extracellular matrix.

PMID- 8562876
TI  - Apoptosis in flat neoplasias of the colorectal mucosa.
AB  - Intraepithelial and intramacrophageal inclusion granules (Leutchenberger bodies)
      were found in 83.9% of 174 flat neoplastic lesions of the colorectal mucosa. Flat
      adenomas with high grade dysplasia and flat adenocarcinomas originating in flat
      adenomas demonstrated a higher proportion of moderate to large (++/ ) numbers of
      granules than flat adenomas with low grade dysplasia, indicating that the
      occurrence of apoptotic granules may be related to the "biological age" of the
      adenoma. Early studies suggest that these inclusions may be the remains of
      intraepithelial lymphocytes. A lymphoid follicle aggre-gate subjacent to flat
      adenomas was recorded in 38% of the cases. Whether the intraepithelial
      lymphocytes derive from the lymphocytes contained in these satellite lymphoid
      aggregates remains unclear. Conventional and immunohistochemical stains
      demonstrated that these inclusions represent apoptotic mate-rial. The possibility
      that tumor cells from flat neoplastic lesions of the colorectal mucosa inflict
      apoptosis upon non-epithelial (i.e. foreign) cells has been entertained.

PMID- 8562877
TI  - Suppressive effects of central opioids on delayed type hypersensitivity to
      trinitrochlorobenzene: comparative study with morphine and electroacupuncture.
AB  - We reported previously that electroacupuncture (Acu) applied to the acu-point
      equivalent to GV4 in the mouse just before the 2,4,6-trinitrochlorobenzene (TNCB)
      challenge suppressed the delayed type hypersensitivity (DTH) through endogenous
      opioidergic systems in the brain, and the pituitary was pivotal in this
      immunosuppression. The purpose of the present study was to compare the
      suppressive effects of Acu with those of single, acute doses of morphine on TNCB
      DTH in intact and hypophysectomized (HPX) mice. Subcutaneous morphine 10 mg/kg in
      ddY mice, 30 mg/kg in BALB/c mice or intracisternal morphine 40 micrograms/mouse
      in BALB/c mice given just before TNCB challenge suppressed (40-53%) the maximal
      extent of ear swelling at 24 hrs after challenge in intact mice. In HPX mice, the
      suppressive effects of intracisternal morphine 10 and 100 micrograms/mouse were
      less pronounced than those observed in intact mice and there was no significant
      difference between intact and HPX groups. In addition, suppressive effects
      observed with Acu or subcutaneous morphine (30 mg/kg) were effectively
      antagonized by pretreatment with intracisternal naloxone at a dose of as low as 2
      micrograms/mouse. Naloxone alone had no effect of its own. These results suggest
      that 1) the activation of opioid receptor-mediated pathways in the brain, which
      occurs when opioids are endogenously released (Acu) or exogenously given
      (morphine), is important in the suppression of TNCB-induced DTH, a cell-mediated
      immune response, and 2) the pituitary is less pivotal in the suppressive effects
      of acute morphine than in those of Acu.

PMID- 8562878
TI  - Influence of glycyrrhizin on the evolution and respiration of Ehrlich ascites
      tumour cells.
AB  - It has been demonstrated that 18 alpha-glycyrrhetinic acid, 18 beta
      glycyrrhetinic acid and glycyrrhizin effectively inhibit the inception and growth
      of skin tumours. Moreover, glycyrrhizin and its aglycone act on the growth and
      differentiation of mouse melanoma cells in culture. In this study we investigated
      the effect of glycyrrhizin, 18 alpha- and 18 beta-glycyrrhetinic acids on the
      evolution of Ehrlich ascites tumour in mice. A prolonged glycyrrhizin treatment
      proved to be effective in modifying the animals' survival pattern.

PMID- 8562879
TI  - Evaluation of the protracted stress in the esophageal mucosa of rats.
AB  - The effect of protracted stress upon the DNA synthesis of the esophageal mucosa
      of the rat was investigated at various time intervals ranging from one to 56
      days. A total of 80 Sprague-Dawley rats were investigated. Lots of 25 rats each
      were either shock-plunged, subjected to swimming in large basins for two hours or
      were only transported to the swimming laboratory and used as controls. The
      remaining 5 rats were non-transported (resting) controls. At the end of the above
      described procedures, all 80 rats received an intraperitoneal injection of 1
      microCi3H-thymidine/gr bodyweight. one hour later the rats were killed. Half of
      the esophagus was processed for DNA extraction and the other half for
      autoradiography. When compared to day 0 (resting control rats), the DNA values in
      experimental animals had increased significantly at day 1, decreased
      significantly at day 7 in swimming rats and risen once again in both experimental
      groups at day 14 and more notably at day 28. By 56 days, the values had reached
      those of day 0. When compared to transported controls at each time interval, both
      experimental groups had significantly higher DNA values at day 1, significantly
      lower at day 7 and once again, significantly higher at day 28. Autoradiographic
      studies of plunged rats showed similar fluctuations in the percentage of labelled
      basal-parabasal cells in the esophageal mucosa at the various time intervals. The
      results of this work are similar to those reported previously for the gastric
      mucosa, the duodenal mucosa and the colonic mucosa of rats subjected to the same
      stressors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562880
TI  - POEMS and Crow-Fukase syndrome: two cases giving rise to more questions about
      plasma cell dyscrasias.
AB  - Two cases of POEMS and Crow-Fukase syndrome are reported. We focused our
      attention on the problems recently debated in the literature regarding POEMS and
      osteosclerotic myeloma, the pathogenetic mechanisms of the clinical symptoms in
      these syndromes and the problems of their classification among plasma cell
      dyscrasias with polyneuropathy.

PMID- 8562881
TI  - Fine structural observations on the human sperm nuclear matrix.
AB  - The nucleus of the mammalian sperm is formed after a series of morphological and
      biochemical changes during spermatogenesis. The human sperm nucleus, after
      sequential extraction with detergents, nuclease and ammonium sulfate, consists of
      a fibroskeletal structure which maintains the original nuclear shape. The
      chromatin-depleted skeleton is formed by thick and thin fibers as well as
      electron-dense patches of different sizes. These highly branched matrix fibers
      had average diameters of 35 and 12 nm. Polarization of the fibroskeletal
      structure is apparent and can be used as a good model to study the function of
      nuclear matrix in nuclear compartmentation in germ cells.

PMID- 8562882
TI  - Detection of EBV DNA in oral squamous cell carcinomas in a black African
      population sample.
AB  - The purpose of this study was to determine the presence of Epstein-Barr virus
      (EBV) DNA in oral squamous cell carcinoma (OSCC) patients from a Black African
      population. Formalin fixed paraffin embedded blocks of OSCC of two randomly
      selected groups were investigated. Group 1 consisting of 57 blocks containing
      OSCC with a fragment of normal appearing adjacent/overlying epithelium. Group 2
      consisted of 48 blocks containing only OSCC tissue without any normal appearing
      epithelium. The control group consisted of 38 non-malignant, non-viral associated
      lesions. A standard polymerase chain reaction (PCR) was used to amplify the Bam
      HI W-fragment using a nested primer set. EBV DNA was demonstrated in 14/57 (25%)
      blocks from Group 1, in 13/48 (27%) blocks from Group 2 and in 16/38 (42%) blocks
      from the control group. No evidence for a direct role of EBV in the process of
      malignant transformation of intraoral epithelial cells was found in this study.

PMID- 8562883
TI  - Tumor cells cultured in vivo in diffusion chambers induce hematological
      alterations.
AB  - We have studied in BALB/c mice the hematological alterations of the host induced
      by the growth of tumor cells in diffusion chambers (DC) In this model, host-tumor
      interactions are only mediated by soluble factors. Tumor cells proliferate and
      grow in DC up to 15 days after implant. Our results show a reversal of the
      granulocyte-lymphocyte ratio in peripheral blood, with lymphopenia and a relative
      increase of myeloid progenitors in the bone marrow of mice bearing DC with M3
      tumor cells (M3TC).

PMID- 8562884
TI  - Flow cytometrical comparison of different nuclear preparation methods upon number
      of DNA-populations and S-phase fraction using fresh and formalin-treated normal
      endometrial tissue.
AB  - In order to compare the flow cytometrically estimated DNA-parameters,
      histopathologically normal uterine mucosa from 250 patients was used. We compared
      the method of Schutte combined with those of Vindelov or Thorntwaite in 250 and
      139 cases respectively. We also compared the concomitant results when using fresh
      or formalin fixated material. Regarding Shutte-Thorntwaite there was no
      significant difference in number of DNA-populations of fresh or formalin-treated
      samples. However, significant differences were found regarding the number of DNA
      populations when comparing Vindelov with Schutte-Vindelov and also between the
      two methods (Shutte-Thorntwaite and Schutte-Vindelov) regarding all parameters
      investigated. Thus we strongly recommend that laboratories test out relevant
      parameters on histopathologically normal material from the organ from which later
      tumor material will be retrieved.

PMID- 8562885
TI  - Influence of diazepam on rat cardiac noradrenergic innervation in response to
      noise stress.
AB  - The effects of pretreatment with a benzodiazepine (diazepam) on the
      cardiovascular system of rats exposed to noise were evaluated. Animals were given
      diazepam before noise treatment; time exposure was one and six consecutive hours.
      Examination of preparations (corresponding portions of right atrium and
      ventricle), obtained using the histofluorescence method, showed that noise
      treatment increased the density of noradrenergic pattern. In diazepam-pretreated
      tissues the fluorescent fibres resulted to be thinner and less numerous, in
      particular after one hour of noise exposure. Our present data demonstrate that
      diazepam exerts a protective action on the heart, more evident after one hour of
      treatment.

PMID- 8562886
TI  - The effect of Toremifene on the expression of some genes in human mononuclear
      cells.
AB  - Toremifene exerts multiple and varied effects on the gene expression of human
      peripheral mononuclear cells. After short-term, in vitro exposure to
      therapeutical levels, distinct changes in P-glycoprotein, steroid receptors, p53
      and Bcl-2 expression take place. In view of the increasing use of antiestrogens
      in cancer therapy and prevention, there is obvious merit in long-term in vivo
      studies to be conducted.

PMID- 8562887
TI  - Studies on the effect of aurintricarboxylic acid (ATA) on cell proliferation of
      renewable epithelial tissues in the mouse.
AB  - The effect of a three-week treatment regimen with 2, 4 or 6 mg aurintricarboxylic
      acid (ATA) per kg body weight on the cell proliferation of jejunal crypts and
      dorsal epidermis of the nude mouse was studied using standard autoradiographic
      methods after in vivo pulse labelling with 3H-thymidine. ATA was slightly toxic
      to the animals in a dose-dependent manner (p < 0.01), as measured by the decrease
      of the rate of weight gain of the treated animals. In the small intestine, ATA
      led to a shrinkage of crypt length by a factor of 10-15% (p < 0.05), mainly by
      inhibiting cell proliferation in a dose-dependent manner (p < 0.05) and only
      secondarily and at higher doses by additionally increasing the cell loss. On the
      contrary, both the 3H-thymidine labelling index and the mitotic index of the
      basal cell layer of the epidermis are found to be increased under treatment with
      ATA. Thus, the present findings indicate that ATA may differentially affect the
      tissue homeostasis of different renewable epithelia in vivo.

PMID- 8562888
TI  - Langerhans cells in nasopharyngeal carcinoma in relation to prognosis.
AB  - Langerhans cells (LC) and macrophages in 119 cases of nasopharyngeal carcinoma
      and 19 cases of nasopharyngeal mucosa obtained from non-cancer patients were
      studied by SPA immunohistochemical methods with the use of antibodies against S
      100 protein and lysozyme, respectively. The distribution of LC in the tumor
      tissue was different from that in macrophages. Patients with dense infiltration
      of LC in the tumor tissue survived longer than those without such infiltration
      (mean survival times, 26.9, 51.7 and 72.6 months in the patients with -, + and ++
      density, respectively: P < 0.005). There was no relationship between patient
      prognosis and density of macrophages (P > 0.25). LC may play an important role in
      tumor immunity and may be taken as one of the criteria of prognosis.

PMID- 8562889
TI  - Vitamin C and the genesis of autoimmune disease and allergy (review).
AB  - The purpose of this review paper is to present relevant information for assessing
      the validity of our clinical investigation on the clinical usefulness of vitamin
      C infusion treatment tested in the control of autoimmune disease and allergy.
      Firstly, we describe the historical background of this study and then present the
      results of both experimental and clinical investigations as regards the
      therapeutic effect of vitamin C infusion treatment for the control of immune
      disorders including diabetes mellitus. Secondly, we discuss the interdisciplinary
      nature of our studies in the light of recent progress in clinical vitaminology,
      endocrinology and immunology. Thirdly, we suggest the possibility that the use of
      our vitamin C infusion treatment may be beneficial in the clinical management of
      AIDS, of which the immunological background data are in favor of the
      participation of an autoimmune mechanism in the genesis of this disease. Finally,
      we stress the importance of paradigm change in the achievement of a breakthrough
      in natural science.

PMID- 8562890
TI  - The high resolution RBG-banded karyotype of Oryctolagus cuniculus. Comparison
      between different classifications of landmarks and bands.
AB  - Representative high resolution RBG-banded haploid karyotypes of Oryctolagus
      cuniculus and corresponding idiograms at the 550 band stage are presented.
      Classification of landmarks and bands based on high resolution RBG- and GTG
      banding are compared with the standard classification and a translation between
      the three systems presented.

PMID- 8562891
TI  - Influence of liposomes rich in unsaturated or saturated fatty acids on the growth
      of human xenotransplanted mammary carcinomas and on the levels of heart type
      fatty acid binding protein.
AB  - A panel of 4 human mammary carcinomas passaged in nude mice were subjected to
      intraperitoneal application of cholesterol-free liposomes enriched with linoleic
      (unsaturated fatty acid) or stearic acid (saturated fatty acid). The liposomes
      were examined with regard to their influence on the tumor growth and level of
      heart type fatty acid binding protein (FABP). Liposomes with different fatty acid
      composition influenced the growth of mammary carcinomas 3366, BO, 4000 and 4151
      in distinct ways. Liposomes with a high content of stearic acid significantly
      inhibited the growth of mammary carcinomas 3366 and BO, whereas mammary
      carcinomas 4000 and 4151 were not affected. The growth of mammary carcinoma 3366
      was moderately increased after supplementation of liposomes rich in linoleic
      acid, the tumor BO was significantly inhibited and the growth of MaCa 4000 and
      4151 was unchanged. Liposome treatment led to a significant increase in heart
      type FABP in mammary carcinomas 3366 and BO regardless of whether the animals
      were treated with liposomes rich in stearic or linoleic acid. Such significant
      changes of FABP level could not be observed in mammary carcinomas 4000 or 4151.
      We suggest that the lipid-mediated growth modulation seems to be dependent on an
      increase of heart type FABPs in these tumor models.

PMID- 8562892
TI  - CD-44: a marker of metastases of head and neck melanomas.
AB  - Specimens of 38 melanomas of the oral cavity and facial skin and 23 lymph nodes
      with melanoma metastases were stained immunohistochemically for the presence of
      variants 5, 6, 7 and 8 of CD-44 antigen. A positive reaction was observed only
      for variant 7-8 in primary melanomas as well as in lymph nodes with metastases
      from melanoma. The CD-44 score (percentage of CD-44 positive cells chi intensity
      of reaction) correlated with metastatic behaviour of tumours and was greater in
      metastatic lymph nodes than in primary tumours.

PMID- 8562893
TI  - Computed tomography in the determination of leg geometry.
AB  - In 286 adults with misalignment of the lower limb the length and torsional angles
      of the femur and tibia were determined using a method based on computed
      tomography. Depending on the location of the axial scan values for femoral
      antetorsion changed substantially. Normal values obtained in non injured
      extremities by this technique were an internal torsion of 23.5 +/- 8.6 degrees
      (mean +/- SD) in the femur and an external torsion of 34.9 +/- 8.6 degrees in the
      tibia. Mean intraindividual side differences in the femur and tibia were 4
      degrees, the 95% confidence interval was 11.0 degrees in the femur and 12.3
      degrees in the tibia. CT-methods can only be used for the determination of
      torsional angles in the femur and tibia if reproducible and standardized
      locations for the acquisition of axial scans are defined.

PMID- 8562894
TI  - Therapeutic effect of CDDP and VP-16 against human bladder cancers.
AB  - In order to evaluate the anticancer effect of combination chemotherapy (CDDP and
      etoposide) against human bladder cancer xenografts transplanted in nude mice, we
      tried an experimental chemotherapy. The tumor was aseptically cut and
      subcutaneously transplanted into the backs of the nude mice. When the weight of
      each tumor reached 300 mg, CDDP (day 1; 4 mg/kg) and etoposide (day 1-5; 2 mg/kg)
      were given intraperitoneally as single agent or in combination and repeated every
      3 weeks. The estimated weight (mg) was obtained by (larger diam. x smaller
      diam.2) x 1/2. A continuous significant effect was observed in CDDP combined with
      etoposide against bladder tumor. Therefore, these results suggest that the
      combination chemotherapy using CDDP with etoposide is an efficacious treatment
      against human bladder cancer.

PMID- 8562895
TI  - Changes in cardiovascular surgical approaches to achieve early extubation.

PMID- 8562896
TI  - Pharmacokinetic and pharmacodynamic principles in providing "fast-track"
      recovery.

PMID- 8562897
TI  - Economic rationale for early extubation.

PMID- 8562898
TI  - Physician and nurse considerations for receiving a "fast-track" patient in the
      intensive care unit.

PMID- 8562899
TI  - Safety issues regarding early extubation after coronary artery bypass surgery.
AB  - Potential safety issues related to early extubation include the effect of changes
      in anesthetic management on intraoperative hemodynamics, stress responses and
      awareness, altered management in the control of pain, shivering and ischemia in
      the early postoperative period, and the risks of reintubation in patients who
      might require reoperation for bleeding. The literature does not implicate any
      technique necessary to facilitate early extubation as being associated with
      adverse outcome. Definitive outcome studies are only beginning to be presented,
      but the data so far suggest that early extubation is not associated with any
      increase risk of mortality or morbidity, including, specifically, myocardial
      ischemia or infarction. These studies of early extubation have involved selected
      patients, and it is unknown but unlikely that early extubation can be recommended
      for all patients, particularly those who might be at risk for perioperative
      ischemia as the result of inadequate myocardial protection, unsatisfactory
      surgery, or other factors yet to be identified. In the absence of definitive
      studies, it may be prudent to manage high-risk patients with a more conservative
      approach. Complications such as low cardiac output, arrhythmias, stroke, and
      perioperative myocardial infarction have not increased with early extubation, at
      least in patients selected for early extubation on the basis of preoperative
      characteristics. In summary, available evidence suggests that early extubation,
      applied to many but probably not all patients, can be accomplished without
      demonstrable patient harm. A coordinated approach involving anesthesia, surgery,
      nursing, respiratory therapy, and other support services is essential, and
      constant reevaluation as events unfold, rather than rigid protocols, allows care
      to be individualized to the specific needs of each patient.

PMID- 8562900
TI  - Practical aspects of early extubation in cardiac surgery.

PMID- 8562901
TI  - Cardiac surgery "fast tracking" in an academic hospital.

PMID- 8562902
TI  - Early extubation: perspective from a community hospital.

PMID- 8562903
TI  - Targeting diphtheria toxin to growth factor receptors.
AB  - Biochemical, genetic and X-ray crystallographic analysis of diphtheria toxin have
      demonstrated that the native toxin is composed of three structural domains that
      function in an ordered fashion to intoxicate a eukoryotic cell. With the
      knowledge that, if delivered to the cytosol, a single molecule of the catalytic
      domain is lethal for the cell, we have used recombinant DNA methods to
      genetically replace the native toxin receptor binding domain with a series of
      growth factors. The resulting diphtheria toxin-related cytokine fusion proteins,
      or fusion toxins bind to their respective receptors, are internalized by receptor
      mediated endocytosis, and efficiently eliminate target cell populations by the
      adenosine diphosphate ribosylation of elongation factor 2. Based upon the results
      of preclinical studies, DAB486IL-2, DAB389IL-2 and DAB389EGF have, or are in the
      process of being evaluated in Phase I/II clinical trials. To date, administration
      of the diphtheria toxin-based fusion proteins targeted toward the high affinity
      IL-2 receptor have been found to be safe, well tolerated, and capable of inducing
      remission in refractory hematologic malignancies.

PMID- 8562904
TI  - Targeting plant toxins to the urokinase and alpha 2-macroglobulin receptors.
AB  - We have conjugated the ribosome-inactivating protein (RIP) saporin to human
      urokinase-type plasminogen activator (uPA), and tested the uPA-saporin conjugate
      for cytotoxicity to uPA receptor-expressing cells. Unlike unconjugated uPA,
      saporin-conjugated uPA did not require any interaction with plasminogen activator
      inhibitors to be internalized. We have shown that saporin, as well as other RIPs,
      binds to the alpha 2-macroglobulin receptor (alpha 2 MR), a cell surface
      glycoprotein that endocytoses uPA-inhibitor complexes. Thus, the uPA receptor
      might present uPA saporm to alpha 2MR for internalization of the conjugate, a
      mechanism similar to that of uPA complexed to specific PA inhibitors. The binding
      of RIPs to alpha 2MR contrasts with previously proposed non-specific mechanisms
      for RIP entry into cells. The implications of the interactions between RIPs and
      alpha 2MR are discussed, with an emphasis on the role of alpha 2MR in mediating
      RIP immunogenicity and immune suppression.

PMID- 8562905
TI  - Tumor targeting through fibroblast growth factor receptors.
AB  - Fibroblast growth factor tyrosine kinase receptors are encoded by four genes, but
      alternate splicing can result in more than 100 possible protein sequences. The
      receptors have widespread expression in the developing embryo, but the expression
      becomes more restricted in the adult. The ligand-receptor relationship is
      complex, due to the diversity of the receptors and the large number of possible
      ligands: there are now nine (and probably more) members of the fibroblast growth
      factor family. This complicated ligand-receptor relationship creates many options
      to target cell types through the use of individual ligands or receptor-specific
      monoclonal antibodies. In-vivo data demonstrate that FGF receptors are expressed
      on tumor cells and can be used to target tumors for growth inhibition. Given the
      complexity, it is possible that a unique targetable FGF receptor isoform can be
      found in one or more tumor types. Examples of the targeting of growth inhibition
      agents to tumors through FGF receptors are discussed.

PMID- 8562906
TI  - Targeted therapy of carcinomas using BR96 sFv-PE40, a single-chain immunotoxin
      that binds to the Le(y) antigen.
AB  - Monoclonal antibody BR96 recognizes a Le(y)-related carbohydrate antigen
      expressed on a wide range of carcinomas. Immunotoxins composed of BR96 and a
      binding defective form of Pseudomonas exotoxin A were constructed both as
      chemical conjugates and as fusion proteins. While both forms of BR96 immunotoxin
      were equally cytotoxic to human carcinoma cell lines in vitro, the fusion protein
      form, BR96 sFv-PE40, was > 10-fold more active in vivo as an antitumor agent.
      BR96 sFv-PE40 was used to target established human tumor xenografts in both mice
      and in rats. The rat which displays the Le(y) antigen on the same normal tissues
      as humans appears to be an appropriate model for the preclinical evaluation of
      this immunotoxin. Complete regressions of lung, breast and bladder carcinomas
      were obtained in these models upon administration of well-tolerated doses of BR96
      sFv-PE40. The clinical limitations of BR96 sFv-PE40, as well as other
      immunotoxins, depend on the management and/or prevention of neutralizing anti
      immunotoxin antibodies and the onset of toxicities, specifically vascular leak
      syndrome.

PMID- 8562907
TI  - Targeting Pseudomonas exotoxin to hematologic malignancies.
AB  - Malignant cells of hematopoietic origin often express a variety of different
      growth factor receptors and antigens on their surface, at levels much higher than
      normal cells. These malignant cells can be selectively targeted with Pseudomonas
      exotoxin (PE) derivatives directed by interleukins 2, 4 and 6, and by Fv
      fragments of monoclonal antibodies to interleukin 2 receptor (IL2R) subunits,
      CD22 and other antigens present on these cells. Anti-Tac(Fv)-PE38, a single-chain
      recombinant immunotoxin which targets cells bearing the IL2Ra, is furthest along
      in preclinical development and is being prepared for clinical testing in patients
      with IL2Ra-positive leukemia, lymphoma and Hodgkin's disease.

PMID- 8562908
TI  - Clinical trials of targeted toxins.
AB  - Immunotoxins (monoclonal antibodies chemically coupled to peptide toxins) and
      fusion toxins (peptide ligands fused genetically to peptide toxins) have been
      used to treat a variety of malignancies over the last 20 years. Problems with
      normal tissue toxicities (vascular leak syndrome, hepatotoxicity, and
      neurotoxicities), poor penetration to tumor interstitum, and humoral immune
      responses have limited clinical efficacy. Higher response rates were observed
      with systemic therapy of leukemias and lymphomas and regional therapy of primary
      brain tumors. Ongoing studies are examining the role of targeted toxins in
      combination with chemoradiotherapy and in minimal residual disease settings.

PMID- 8562909
TI  - Interplay between nucleosomes and transcription factors at the yeast PHO5
      promoter.
AB  - In this review, we summarize experiments which have used the yeast PHO5 gene to
      determine the functional consequences of nucleosome structure in the promoter
      region. In the PHO5 system, nucleosomes participate in promoter repression by
      interfering with factor binding. Therefore, disruption of nucleosome structure is
      likely a prerequisite for promoter activation. There still remain several
      important questions regarding the assembly and disassembly of chromatin
      repression. Recent experiments have shown that the PHO5 chromatin transition is
      replication and transcription independent. Nucleosome disruption does, however,
      depend upon binding of a transactivator, Pho4, to the PHO5 promoter. Moreover,
      the activation domain of Pho4 appears to play a critical role in chromatin
      disruption.

PMID- 8562910
TI  - Drosophila chromatin and transcription.
AB  - In Drosophila transcription is differentially repressed by various aspects of
      chromatin, thought to represent distinct structural levels: the nucleosome core
      particle, the linker histone H1 and as yet undefined higher order structures.
      Heterochromatin serves as a paradigm for the latter level of organization, but
      maintenance of silencing at homeotic gene loci may also fall into this class.
      Recently GAGA transcription factor (GAF) was shown to counteract chromatin
      repression at all levels. The various effects of GAF could be explained by its
      ability to rearrange nucleosomal positions. Chromatin remodelling by GAF and
      other factors in vitro require activities that maintain a highly dynamic state of
      chromatin.

PMID- 8562911
TI  - Chromatin and transcriptional activity in early Xenopus development.
AB  - Experiments with Xenopus oocytes and embryos have determined a direct biochemical
      relationship between chromatin structure and transcription. Nucleosomes within
      specific nucleoprotein architectures can either activate or repress
      transcription. Developmentally regulated changes in chromosomal composition
      direct the dominant repression of specific genes. Reconstruction of chromatin
      templates in vivo establishes that replication-coupled chromatin assembly both
      represses basal transcription and facilitates a full range of inducible gene
      activity. Chromatin structure emerges as a major contributory factor to the
      regulation of genes.

PMID- 8562912
TI  - Role of chromatin structure in zygotic gene activation in the mammalian embryo.
AB  - Changes in chromatin structure, rather than changes in the activity of the
      transcriptional apparatus, may underlie the timing and basis for zygotic gene
      activation in the mouse embryo. The transcriptional capacity of the male and
      female pronuclei differs and the first mitosis is associated with development of
      a transcriptionally repressive state such that efficient gene expression requires
      a functional enhancer. This repressive state is also relieved by increasing the
      level of histone H4 hyperacetylation. Zygotic gene activation is also associated
      with the transient enrichment of chromatin containing hyperacetylated histone H4
      and RNA polymerase II at the nuclear periphery. Depletion of maternally-derived
      histones as the signal for zygotic gene activation is explored.

PMID- 8562913
TI  - Nucleoprotein architecture of the albumin transcriptional enhancer.
AB  - Studies of the serum albumin gene have shown that in the active state, its tissue
      specific enhancer is organized with transcription factors into nucleoprotein
      structures that appear nucleosomal. Thus, the organization of chromatin
      components, and not their disruption or absence, is intrinsic to enhancer
      activity. Mechanisms for creating the nucleosome-like array are discussed with
      regard to the developmental control of cell-specific gene expression.

PMID- 8562914
TI  - Histone phosphorylation during sea urchin development.
AB  - Studies on histone phosphorylation during transitions in chromatin structure
      occurring in vivo during spermatogenesis and early embryogenesis in sea urchins
      are reviewed and evaluated in the light of recent studies on histone
      phosphorylation occurring during chromatin synthesis in frog egg extracts in
      vitro and evidence that protein kinases and phosphatases play direct roles in the
      regulation of cellular structure. Sperm-specific histone variants Sp H1 and Sp
      H2B are maintained as phosphorylated derivatives N and O/P throughout
      spermatogenesis and early embryogenesis and egg specific histone variants CS H1
      and CS H2A are phosphorylated during early embryogenesis. These developmental
      correlations provide clues about the roles of histone phosphorylation in control
      of chromatin structure in vivo and provide a basis for the interpretation of data
      obtained from in-vitro sperm chromatin remodeling in egg extracts and from
      biochemical studies on the effects of histone phosphorylation on DNA binding. The
      potential consequences for chromatin structure of the various histone
      phosphorylation events observed in sea urchins and frog egg extracts are
      discussed.

PMID- 8562915
TI  - Histone acetylation in chromatin and chromosomes.
AB  - The packaging of DNA into chromatin is an important regulator of transcription.
      This regulation may operate either by short-term switching of the transcription
      of specific genes or by packaging chromosome domains into structures that either
      facilitate or repress the potential for gene expression. Such packaging may occur
      during chromatin assembly through S-phase of the cell cycle. Recent evidence
      shows that the post-translational acetylation of histones of the nucleosome core
      particle is intimately involved in all these processes. New approaches allowing
      exploration of the molecular details, the functional effects and the regulation
      of histone acetylation promise to reveal new mechanisms of genomic regulation.

PMID- 8562916
TI  - Selective distribution of histone H1 variants and high mobility group proteins in
      chromosomes.
AB  - Recent results on the differential distribution of sequence variants of histone
      H1, of proteins of the HMG 1/2 family, and of HMG1 in polytene chromosomes are
      reviewed. Several organisms are known to contain two different HMG 1/2 proteins.
      In Chironomus, one of them is restricted to decondensed puffs and may have a
      specific function. One of the H1 variants of Chironomus is found only in a
      minority of chromosome bands and differs from the other H1 proteins of the
      organism by genomic organization and by an inserted structural motif that is also
      present in single H1 variants of other organisms.

PMID- 8562917
TI  - The HMG-14/-17 chromosomal protein family: architectural elements that enhance
      transcription from chromatin templates.
AB  - Chromosomal proteins HMG-14 and HMG-17 enhance the transcriptional potential of
      chromatin when incorporated into nucleosomes during, but not after, chromatin
      assembly on replicating DNA. Two molecules of either HMG-14 or HMG-17 can bind to
      nucleosome cores, independently of the underlying DNA sequence, in a cooperative
      fashion to limit nucleosome mobility and stabilize the structure of the
      nucleosome core without stabilizing the higher order chromatin structure. By
      modifying the structure of nucleosomes, the proteins affect the local structure
      of the chromatin fiber leading to an increase in the rate of transcriptional
      elongation but not initiation. We suggest that HMG-14/-17 are architectural
      elements which assist in the assembly of an unfolded chromatin fiber thereby
      decreasing the repressive activity of histones and facilitating transcriptional
      processes.

PMID- 8562918
TI  - Cellular regulation of the protein C pathway.
AB  - The protein C anticoagulant pathway regulates thrombin formation. The pathway is
      triggered when thrombin binds to the endothelial cell proteoglycan,
      thrombomodulin. Unlike thrombin, this complex is a potent activator of the
      protein C zymogen, but it cannot clot blood. Activated protein C binds to protein
      S on cell surfaces where it proteolytically inactivates coagulation factors Va
      and VIIIa. Activated protein C also binds to a newly identified endothelial
      protein C receptor. Congenital deficiencies in this pathway are associated with
      thrombotic disease, and inflammation can cause acquired deficiencies. Activated
      protein C appears to inhibit inflammation. Thus, this pathway modulates both
      coagulation and inflammation.

PMID- 8562919
TI  - Inflammatory cell participation in coagulation.
AB  - Vascular cells, and leukocytes in particular, have evolved a formidable machinery
      to initiate and amplify coagulation. Through multiple, receptor-mediated
      recognitions this process provides a cellular microenvironment of limited
      proteolytic activation that contributes to the maintenance of the hemostatic
      balance in vivo. However, the ability of leukocytes to generate thrombin is also
      a fundamental aspect of inflammatory responses, and has far-reaching implications
      in the pathophysiology of vascular diseases. The scope of this article is to
      revisit the most recent contributions to the cellular and molecular mechanisms of
      leukocyte-mediated coagulation, and to highlight their role in the pathogenesis
      of vascular injury.

PMID- 8562920
TI  - Induction of cellular procoagulant activity by the membrane attack complex of
      complement.
AB  - In addition to their well-recognized role in immune defense, there is a growing
      recognition that the proteins of the complement system impact directly on
      vascular homeostatic mechanisms, evoking cellular responses that serve to both
      promote adherence of blood cells to the walls of blood vessels, and the formation
      of fibrin through the enzyme mechanisms of the coagulation system. This clot
      promoting or 'procoagulant' activity initiated through the complement system
      entails both receptor-mediated as well as receptor-independent pathways of cell
      activation. In this review, we will focus specifically upon the role that is now
      thought to be played by the membrane attack complex of the complement system
      (MAC) in the induction of the procoagulant properties of human platelets and
      endothelium.

PMID- 8562921
TI  - Hypoxia and modification of the endothelium: implications for regulation of
      vascular homeostatic properties.
AB  - Hypoxia is a common denominator of ischemic microenvironments. Endothelium
      subjected to oxygen deprivation maintains cell viability and basic biosynthetic
      mechanisms, but displays multiple changes in properties relevant to vascular
      homeostasis, including suppression of the anticoagulant cofactor thrombomodulin,
      decreased barrier function, and generation of proinflammatory cytokines.
      Diminished intracellular cAMP during the period of hypoxia and lowered nitric
      oxide/cGMP in the subsequent reperfusion period are proposed as fundamental
      mechanisms driving vascular dysfunction impacting on coagulation, permeability,
      vasomotor tone and leukocyte adhesivity. The period of organ preservation for
      transplantation, recognized to be associated with hypoxia, primes mechanisms
      leading to subsequent vascular dysfunction which can be ameliorated by
      buttressing cAMP and nitric oxide/cGMP intra- and intercellular second messenger
      systems. A mechanism likely to contribute to hypoxia-mediated generation of
      cytokines, such as interleukin 6, is activation of the transcription factor NF-IL
      6, which occurs in oxygen deprivation. These data indicate that study of cellular
      mechanisms of endothelial perturbation in hypoxia is likely to provide insights
      ultimately applicable to ischemia-induced vascular damage.

PMID- 8562922
TI  - Platelet-activating factor mediates procoagulant activity on the surface of
      endothelial cells by promoting leukocyte adhesion.
AB  - Endothelial cells co-express platelet-activating factor and P-selectin on their
      surfaces after activation by certain receptor-mediated agonists. Together they
      mediate the adhesion of leukocytes to the endothelial cell surface. P-selectin
      tethers leukocytes to the endothelial cell surface allowing leukocyte activation
      by platelet-activating factor. Adhesion and activation are specific for
      leukocytes because they are the only cells known to express the ligand for P
      selectin. Leukocytes adherent to the endothelial cell surface may promote
      thrombosis by three mechanisms: (1) they secrete factors that damage the
      underlying endothelium, (2) they secrete factors that directly initiate the
      coagulation cascade, and (3) they bind and activate platelets.

PMID- 8562923
TI  - Platelet adhesion receptors.
AB  - The response to vascular injury involves attachment and aggregation of platelets,
      coupled with initiation of the coagulation cascade. These inter-related processes
      ensure that the vessel injury is rapidly blocked with an aggregated clump of
      platelets that is then stabilized by a crosslinked fibrin matrix. Initial
      adherence relies on the ability of the platelet adhesion receptors to bind
      subendothelial matrix molecules. Platelet activation then results in the
      expression of high affinity integrin receptors on the cell surface that bind
      soluble ligands, allowing platelets to aggregate and form a haemostatic plug.

PMID- 8562924
TI  - Molecular and cellular basis for type I heparin cofactor II deficiency (heparin
      cofactor II Awaji).
AB  - Heparin cofactor II (HCII) is a serine proteinase inhibitor in human plasma that
      rapidly inhibits thrombin in the presence of dermatan sulfate or heparin. To
      understand the molecular mechanism for HCII deficiency in a patient with reduced
      circulating HCII antigen, we studied a Japanese patient with type I HCII
      deficiency who suffered from angina pectoris and coronary artery disease.
      Polymerase chain reaction (PCR)-based sequence analysis showed that the
      propositus' gene for HCII (HCII Awaji gene) had a thymine insertion after codon
      (GAT) for Asp88 in exon II, resulting in a frameshift mutation. Consequently, the
      abnormal HCII Awaji protein was suggested to have an altered amino acid sequence
      from position 89 and terminate at 107, thus being composed of the NH2-terminal
      one fifth of normal HCII and dysfunctional for thrombin inhibition. The molecular
      weight and pI value of HCII Awaji were calculated to be 12,040 and 3.6,
      respectively, without posttranslational modification. Mutagenic PCR followed by
      the Tsp509I digestion showed that a half of the PCR products derived from the
      propositus and his sister was cleaved, suggesting that his sister also has the
      same mutant allele. Crossed-immunoelectrophoresis and Western blot analyses of
      plasma and urine from the the propositus and of plasma from his sister did not
      provide evidence for the existence of the abnormal HCII, suggesting that little
      truncated HCII was circulating in the patient's blood. However, stable expression
      assay using human kidney 293 cells transfected with the expression vector
      containing cDNA encoding wild-type or Awaji-type HCII showed that mutant as well
      as wild-type HCII was secreted into culture medium normally. These results
      suggest that the abnormal HCII Awaji protein is secreted normally, but rapidly
      degraded in the circulating blood.

PMID- 8562925
TI  - The defective interaction between von Willebrand factor and factor VIII in a
      patient with type 1 von Willebrand disease is caused by substitution of Arg19 and
      His54 in mature von Willebrand factor.
AB  - In this report we describe the further investigation of the von Willebrand factor
      (vWF)/FVIII interaction in a type 1 von Willebrand disease patient characterized
      by discrepant VIII:C levels as determined by one-stage and two-stage VIII:C
      assays. A solid-phase binding assay shows that this patient's plasma vWF is
      moderately defective in capturing recombinant FVIII. Sequence analysis of the
      FVIII-binding domain encoded by the vWF mRNA of the affected individual
      identified mutations in both vWF alleles. In allele A, the mutations C2344T and
      T2451A result in the substitution of Trp for Arg19 (R19W) and of G1n for His54
      (H54Q) in mature vWF, respectively. This allele also contains a reported
      polymorphism (A2365G, Thr26Ala). Allele B, which is underexpressed at the RNA
      level, contains a one-nucleotide deletion in the FVIII-binding domain (delta
      G2515) that results in the premature termination of translation. Analysis of the
      binding of FVIII by full-length vWF transiently expressed in COS-7 cells confirms
      that the combined R19W and H54Q substitutions are the cause of the defective
      vWF/FVIII interaction in this patient. The FVIII-binding defect of vWF containing
      either mutation alone is approximately half that of the double mutant, which
      suggests that the effect of these mutations is additive. The mutant proteins are
      recognized equally well by vWF monoclonal antibodies MBC105.4, 32B12, and 31H3,
      which block the binding of FVIII by vWF, indicating that amino acids Arg19,
      Thr26, and His54 are not critical residues in the epitopes of these antibodies.

PMID- 8562926
TI  - Interleukin-13 inhibits interleukin-2-induced proliferation and protects chronic
      lymphocytic leukemia B cells from in vitro apoptosis.
AB  - Human interleukin-13 (IL-13) acts at different stages of the normal B-cell
      maturation pathway with a spectrum of biologic activities overlapping those of IL
      4. B chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of
      slow-dividing and long-lived monoclonal B cells, arrested at the intermediate
      stage of their differentiation. In vitro, B-CLL cells exhibit a spontaneous
      apoptosis regulated by different cytokines. In this report, we show that IL-13
      (10 to 200 ng/mL) acts directly on monoclonal B-CLL cells from 12 patients. (1)
      IL-13 enhances CD23 expression and induces soluble CD23 secretion by B-CLL cells
      but does not exhibit a growth factor activity. (2) IL-13 inhibits IL-2
      responsiveness of B-CLL cells, activated either with IL-2 alone or through
      crosslinking of lgs or ligation of CD40 antigen. (3) IL-13 protects B-CLL cells
      from in vitro spontaneous apoptosis. The effects of IL-13 on neoplasic B cells
      were slightly less than those of IL-4 and occurred independently of the presence
      of IL-4. The present observations show that IL-13 may exhibit a negative
      regulatory effect on neoplasic B cells in contrast with that observed in normal B
      cells, and suggest that IL-13 could be an important factor in the pathogenesis of
      CLL by preventing the death of monoclonal B cells. Moreover, B-CLL may be an
      interesting model to study the regulation of the expression of IL-13 receptor
      and/or signal transduction pathways.

PMID- 8562927
TI  - A deletion in the proximal untranslated pX region of human T-cell leukemia virus
      type II decreases viral replication but not infectivity in vivo.
AB  - The function of untranslated (UT) nucleotide sequences in the proximal portion of
      the pX region of the human T-cell leukemia virus (HTLV) family of retroviruses
      remains enigmatic. Previous studies have shown that these sequences are not
      necessary for the expression of viral proteins or for the induction,
      transmission, or maintenance of the transformed cell type in vitro. To determine
      the effect of the UT region in vivo, separate groups of rabbits were inoculated
      with lethally irradiated, stable clones of the human B-lymphoblastoid cell line,
      729, transfected with either a full-length wild-type HTLV-II clone (pH6neo) or a
      mutant clone containing a 324-bp deletion in the proximal UT portion of pX
      (pH6neo delta UT[6661-6984]), or nontransfected 729 cells. All rabbits inoculated
      with either wild-type or pX-deleted HTLV-II developed a similar profile and titer
      of serum antibodies against HTLV-II antigens, as determined by Western
      immunoblots, by 4 weeks postinoculation (PI). Antibody titers, as determined by
      enzyme immunoassay, were similar between the two groups of rabbits and increased
      over the 18-week period of study. All rabbits were killed at 18 weeks PI, and
      spleen, peripheral blood lymphocytes (PBMC), bone marrow, and mesenteric lymph
      node were assayed for HTLV-II tax/rex sequences by quantitative polymerase chain
      reaction. Virus was detected in all tissues tested from all rabbits inoculated
      with 729pH6neo cells containing wild-type HTLV-II, which contained between 1.4
      and 0.3 mean copies of provirus per cell. In contrast, the distribution and
      number of provirus copies were more limited in rabbits inoculated with 729pH6neo
      delta UT(6661-6984) cells containing UT-deleted HTLV-II; in most tissues, there
      was a fivefold to sevenfold reduction in mean provirus copies per cell as
      compared with rabbits inoculated with wild-type HTLV-II. All rabbits inoculated
      with control 729 cells remained negative for HTLV-II infection, as determined by
      the same techniques. It was concluded that UT sequences in the proximal portion
      of HTLV-II are not necessary for infection but confer increased replicative
      capacity in vivo.

PMID- 8562928
TI  - Analysis of the Bruton's tyrosine kinase gene promoter reveals critical PU.1 and
      SP1 sites.
AB  - The gene defective in X-linked agammaglobulinemia (XLA) encodes a novel protein
      kinase termed Bruton's tyrosine kinase (Btk). Whereas the XLA phenotype is
      confined to abnormalities of B-cell development and function, Btk is expressed
      not only in B-lymphocyte lineage but also in myeloid lineage cells. The first 450
      basepairs of the Btk promoter fused to a luciferase gene displayed a similar cell
      type specificity. Critical binding sites for the transcription factors PU.1 and
      Sp1 were identified in the proximal portion of the Btk promoter upstream of a
      cluster of transcriptional start sites. Mutation of either the PU.1 or Sp1 site
      markedly reduced the activity of a Btk promoter-luciferase reporter construct in
      transfection experiments. In addition, PU.1 directly transactivated the Btk
      promoter, and deletion of the PU.1 binding site abolished this effect. This study
      implicates PU.1 and Sp1 as major regulators of Btk expression and provides a
      foundation for further study of the regulation of this gene in XLA patients that
      lack Btk mRNA.

PMID- 8562929
TI  - Epstein-Barr virus genome in non-Hodgkin's lymphomas occurring in immunocompetent
      patients: highest prevalence in nonlymphoblastic T-cell lymphoma and correlation
      with a poor prognosis. Danish Lymphoma Study Group, LYFO.
AB  - A series of 520 cases of non-Hodgkin's lymphoma (NHL; 374 of B-cell, 130 of T
      cell, 5 of non-B/non-T-cell, and 11 of undetermined phenotype) was analyzed for
      the presence of Epstein-Barr virus (EBV) using RNA in situ hybridization (RISH).
      The aims of the study were to assess the frequency of EBV-encoded small nuclear
      RNAs 1 and 2 (EBER), abundant immediate early RNAs (BHLF), and latent membrane
      protein-1 (LMP-1) in cases covering the entire histologic spectrum of NHL, and to
      analyze whether EBV status had prognostic relevance with regard to patient
      survival. EBER positivity was found in 25 of 374 (7%) B-NHL and 40 of 130 (31%) T
      NHL (P < .00005) cases, but in only 1 of 16 cases with non-B/non-T-cell or
      undetermined phenotype. Among T-NHL cases, EBER positivity was confined to
      angioimmunoblastic, lymphadenopathy-like lymphoma (11 of 13 cases, 85%),
      Lennert's lymphoma (five of seven cases, 71%), and pleomorphic T-NHL (24 of 67
      cases, 36%). Mycosis fungoides, lymphoblastic, and CD30-positive anaplastic large
      T-cell NHL cases were consistently EBV-negative. Double-labeling by RISH and
      immunophenotyping demonstrated the presence of EBV in neoplastic T cells, but no
      CD21 expression was found in the EBER-positive T-NHL cases. LMP-1 was expressed
      in 12 of 40 (30%) EBER-positive T-NHL and 5 of 25 (20%) EBER-positive B-NHL
      cases. For both T- and B-NHL, no correlation was found for EBER positivity and
      age, sex, clinical stage, or serum level of lactate dehydrogenase (LDH) at
      diagnosis. However, in T-NHL but not B-NHL, EBER positivity correlated with the
      presence of constitutional symptoms and a poor performance score (PS < 1; scale,
      0 to 4). EBER status did not have any prognostic significance in B-NHL, but it
      had a negative prognostic impact in high-grade T-NHL (7-year survival of EBER
      negative v EBER-positive cases: 33% v 14%; P = .01). A multivariate analysis
      including all B- and T-NHL of intermediate-/high-grade histology showed that EBER
      positivity in T-NHL was one of the three most significant factors recognized by
      the final prognostic model, only surpassed by PS greater than 1 and age greater
      than 67 years, and more powerful than B symptoms, an elevated LDH, or
      disseminated disease (clinical stage greater than II). We conclude that patients
      with EBV-positive T-NHL have a very poor clinical outcome, that EBV status should
      be considered as additional useful information in the classification of T-NHL,
      and that EBV-positive T-NHL should be treated as a separate entity in the future.

PMID- 8562930
TI  - Elevated intracellular level of basic fibroblast growth factor correlates with
      stage of chronic lymphocytic leukemia and is associated with resistance to
      fludarabine.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by delayed senescence and
      slow accumulation of monoclonal, small lymphocytes. Basic fibroblast growth
      factor (bFGF) is a pleiotropic cytokine that plays a role in hematopoiesis and
      apoptosis. Elevated bFGF levels have been detected in urine from patients with a
      variety of neoplastic diseases including various leukemias; however, the cellular
      source of the bFGF has not been determined. In this study, the intracellular bFGF
      level in lymphocytes of 36 patients with B-CLL and 15 normal donors was
      determined using an enzyme-linked immunoassay. In cells derived from patients
      with high-risk disease, the median level of intracellular bFGF was 381.5 pg/2 x
      10(5) cells, compared with a median of 90.5 pg/2 x 10(5) cells in patients with
      intermediate disease. In patients with low-risk disease, the median bFGF level
      was 4.9 pg/2 x 10(5) cells, and in normal controls, it was 6.0 pg/2 x 10(5)
      cells. The difference in the bFGF levels was significant for the comparison
      between low- and intermediate-risk (P = .00119), low- and high-risk (P < .0001),
      and intermediate- and high-risk disease (P = .0001). Immunofluorescent stains of
      peripheral blood mononuclear cells confirmed CLL lymphocytes as a cellular source
      of bFGF. To evaluate the potential contribution of elevated intracellular bFGF
      levels to the phenotype of CLL cells, leukemic cells were cultured in vitro with
      an apoptotic stimulus (fludarabine). CLL cells with high intracellular levels of
      bFGF appeared to be more resistant to fludarabine treatment. The addition of bFGF
      to fludarabine-treated CLL cells resulted in a delay of apoptosis and prolonged
      survival. These data suggest that bFGF may contribute to the resistance of CLL
      cells to an apoptotic stimulus.

PMID- 8562931
TI  - Expression of the p53 tumor suppressor gene induces differentiation and promotes
      induction of differentiation by 1,25-dihydroxycholecalciferol in leukemic U-937
      cells.
AB  - Leukemic U-937 cells, which lack normal p53, were stably transfected with a
      temperature-sensitive mutant of p53 to investigate the consequences for growth
      and differentiation. On induction of wild-type p53 activity at the permissive
      temperature, some of these cells underwent maturation as judged by the capacity
      for oxidative burst and the appearance of monocyte related cell surface
      molecules. Moreover, wild-type p53-expressing cells were more sensitive than p53
      negative control cells to induction of differentiation by 1,25
      dihydroxycholecalciferol; a twofold to fourfold increase of the fraction of cells
      showing signs of terminal maturation was observed when wild-type p53-expressing
      cells were incubated with 1,25-dihydroxycholecalciferol at concentrations that
      only slightly affected control cells. Whereas wild-type p53 activity per se
      induced maturation of certain cells, other underwent cell death judging from the
      reduced capability to exclude trypan blue and the appearance of fragmented DNA in
      flow cytometric analysis. The p53-induced cell death could be inhibited by
      incubation with 1,25-dihydroxy-cholecalciferol, but not all-trans retinoic acid.
      Thus, 1,25-dihydroxycholecalciferol, seemed to increase the survival of wild-type
      p53-expressing cells and to cooperate with wild-type p53 to induce
      differentiation. The data imply that p53-mediated maturation in U-937 cells
      depends on optimal regulation of signals for differentiation, survival and
      proliferation, and suggest a role for p53 in the differentiation induction of
      leukemic cells.

PMID- 8562932
TI  - Consistent amounts of acute leukemia-associated P190BCR/ABL transcripts are
      expressed by chronic myelogenous leukemia patients at diagnosis.
AB  - In chronic myelogenous leukemia (CML), the Philadelphia (Ph) chromosome
      translocation results in the formation of BCR/ABL genes, normally transcribed in
      two types of hybrid transcripts with a b2a2 or b3a2 BCR/ABL junction, which give
      origin to 210-kD fusion proteins (P210). A third type of BCR/ABL (with e1a2 type
      of junction) has been identified in approximately 50% of the Ph-positive acute
      lymphoblastic leukemia (Ph+ALL) cases and results in the production of a BCR/ABL
      protein of 190 kD (P190). The presence of this transcript has been associated
      almost exclusively with the presence of an acute leukemia phenotype. By contrast,
      here we describe that in addition to transcripts with the b2a2 and b3a2 types of
      junction corresponding to the P210 proteins, virtually all CMLs at diagnosis bear
      also BCR/ABL transcripts showing the e1a2 type of junction, which correspond to
      the acute leukemia-associated P190 protein. With a quantitative polymerase chain
      reaction assay we found that the amount of the e1a2 mRNA present in CMLs in
      chronic phase, although in absolute amount much lower than that present in Ph+
      ALLs, represents in most cases approximately 20% to 30% of the total BCR/ABL
      transcripts. Moreover, using a novel and very sensitive Western blot technique,
      we detected relevant amounts of P190 protein in addition to P210 from peripheral
      cells of two of the patients.

PMID- 8562933
TI  - Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic
      large cell lymphoma (Ki-1) and Hodgkin's disease.
AB  - The precise cellular origin and the pathogenetic mechanism(s) leading to the
      neoplastic transformation of anaplastic large cell lymphoma (ALCL) and the Reed
      Sternberg cell of Hodgkin's disease (HD) remains largely uncertain. Classical
      cytogenetic analysis has shown a unique translocation involving bands 2p23 and
      5q35 bands in a variable number of ALCLs. It has been recently shown that the
      nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK;
      2p23) are the fused genes of t(2;5). To investigate the presence and the precise
      frequency of NPM-ALK gene products among ALCL and HD cases, a large and well
      characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using
      multiple strategies including reverse transcriptase-polymerase chain reaction (RT
      PCR), Southern blot analysis, and immunohistochemistry. Overall, 6 (3 T and 3
      null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD
      showed the presence of NPM-ALK transcripts by RT-PCR. NPM-ALK gene rearrangements
      were detected in all RT-PCR, NPM-ALK-positive ALCL by Southern blot analysis.
      Furthermore, in all the available cases we were able to show the presence of ALK
      related protein using a specific polyclonal antiserum recognizing the cytoplasmic
      domain of ALK by immunohistochemistry. Our data show that NPM-ALK gene
      transcripts are identified in a subpopulation of ALCL, almost exclusively in T or
      null cell in origin, and in rare cases of HD. These findings show that some HD
      may be closely related to ALCL, giving us new insights on the pathogenesis and
      possibly biologic evolution of HD.

PMID- 8562934
TI  - Expression of the hematopoietic growth factor receptor FLT3 (STK-1/Flk2) in human
      leukemias.
AB  - Normal expression of the hematopoietic growth factor receptor FLT3 (STK-1@Flk2)
      is limited to CD34+ stem/progenitor cells. We have evaluated the expression of
      FLT3 by RNase protection assay and Western blotting in 161 primary bone marrow
      (BM) samples from patients with leukemia. FLT3 RNA was found to be expressed at a
      higher level than in normal BM controls in 33 of 33 B-lineage acute leukemias, 11
      of 12 acute myeloid leukemias (AMLs), and 3 of 11 T-cell acute leukemias (T
      ALLs). Expression of FLT3 RNA was also observed in some cases of blast crisis
      CML. The FLT3 signal resulted from expression on the leukemic blasts, and was not
      caused by increased FLT3 expression on normal CD34+ stem/progenitor cells in the
      leukemic samples. To determine if FLT3 protein was also overexpressed, proteins
      were extracted from leukemic BM samples and screened by Western blotting with
      anti-FLT3 antisera. FLT3 protein was not detected in normal BM controls, but was
      found in 14 of 14 B-lineage ALLs, 36 of 41 AMLs, and 1 of 4 T-ALLs. Stimulation
      of patient samples with FLT3 ligand resulted in autophosphorylation of the FLT3
      receptor, suggesting the receptor is functional in these cells. These data show
      that FLT3 RNA and protein are aberrantly expressed by AML and ALL cells in that
      CD34 expression and FLT3 expression are no longer synchronous, and suggest the
      possibility that overexpression of FLT3 could play a role in the survival and/or
      proliferation of malignant clones in acute myeloid and lymphoid leukemias.

PMID- 8562935
TI  - Induction of cyclophosphamide-resistance by aldehyde-dehydrogenase gene transfer.
AB  - The identification of genes inducing resistance to anticancer chemotherapeutic
      agents and their introduction into hematopoietic cells represents a promising
      approach to overcome bone marrow toxicity, the limiting factor for most high-dose
      chemotherapy regimens. Because resistance to cyclophosphamide has been correlated
      with increased levels of expression of the aldehyde-dehydrogenase (ALDH1) gene in
      tumor cell lines in vitro, we tested whether ALDH1 overexpression could directly
      induce cyclophosphamide resistance. We have cloned a full-length human ALDH1 cDNA
      and used retroviral vectors to transduce it into human (U937) and murine (L1210)
      hematopoietic cell lines that were then tested for resistance to maphosphamide,
      an active analogue of cyclophosphamide. Overexpression of the ALDH1 gene resulted
      in a significant increases in cyclophosphamide resistance in transduced L1210 and
      U937 cells (50% inhibition concentration [IC50], approximately 13 mumol/L). The
      resistant phenotype was specifically caused by ALDH1 overexpression as shown by
      its reversion by disulfiram, a specific ALDH1 inhibitor. ALDH1 transduction into
      peripheral blood human hematopoietic progenitor cells also led to significant
      increases (4- to 10-fold; IC50, approximately 3 to 4 mumol/L) in cyclophosphamide
      resistance in an in vitro colony-forming assay. These findings indicate that
      ALDH1 overexpression is sufficient to induce cyclophosphamide resistance in vitro
      and provide a basis for testing the efficacy of ALDH1 gene transduction to
      protect bone marrow cells from high-dose cyclophosphamide in vivo.

PMID- 8562936
TI  - Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow
      stromal cells involves activation of NF-kappa B.
AB  - Adhesion of multiple myeloma (MM) cells to bone marrow stromal cells (BMSCs) not
      only localizes MM cells in the marrow microenvironment, but also triggers
      interleukin-6 (IL-6) secretion by BMSCs and related MM cell proliferation. In the
      present study, we characterized the regulation of IL-6 gene expression in BMSCs
      during MM cell adhesion. Adhesion of ARH-77, HS-Sultan, IM-9, and U266 MM cell
      lines to BMSCs and BMSC lines (LP 101 and AA 101) triggered 5-through 15-fold and
      2-through 4-fold increases in IL-6 secretion, respectively. IL-6 mRNA transcripts
      were undetectable by Northern blotting in IM-9 MM cells or LP 101 BMSCs cultured
      alone; however, adherence of IM-9 cells to LP 101 cells induced a transient
      increase in IL-6 transcripts at 6 hours, followed by peak IL-6 secretion at 24
      hours. To confirm increased IL-6 transcription and characterize its regulation,
      LP101 BMSCs were transiently transfected with full length and deletion fragments
      of the IL-6 promoter linked to the chloramphenicol acetyltransferase (CAT)
      reporter gene. Transient transfection of LP101 BMSCs with plasmid containing an
      intact NF-kappa B site showed a 6.8 +/- 0.4-fold increase in CAT activity
      triggered by IM-9 MM cell adhesion (n = 3, P < .05). Transfection of LP 101 cells
      with plasmid containing a single base pair deletion from the NF-kapp B binding
      motif abolished the MM adhesion-induced increase in CAT activity, whereas
      transfection with plasmid containing three copies of synthetic NF-kappa B
      sequence resulted in an 8.1 +/- 0.7-fold increase in CAT activity related to MM
      adhesion (n = 3, P < .05). These data suggest that the NF-kappa B site is one of
      the essential regulatory elements for MM cell adhesion-induced IL-6 transcription
      in BMSCs. Electrophoretic mobility shift assays confirmed the involvement of NF
      kappa B activation in regulating MM adhesion-induced IL-6 transcription in BMSCs.
      Further characterization of the upstream events in the signalling cascade
      regulating IL-6 may not only delineate mechanisms of IL-6 regulation during
      paracrine MM cell growth, but also provide new therapeutic strategies based on
      interruption of IL-6 mediated tumor cell growth.

PMID- 8562937
TI  - BCR-ABL does not prevent apoptotic death induced by human natural killer or
      lymphokine-activated killer cells.
AB  - The erythromyeloid cell line, K562, the most sensitive target in human natural
      killer (NK) cell mediated cytotoxicity, is derived from a chronic myeloid
      leukemia (CML) patient and expresses the characteristic reciprocal translocation
      t(9;22). The resulting BCR-ABL fusion protein has been shown to mediate the
      unusual resistance of K562, and other BCR-ABL expressing lines, to apoptosis
      induced by a variety of agents (irradiation, UV light, cytotoxic drugs). Here we
      show that human NK and lymphokine-activated killer (LAK) cells, when tested at
      low effector to target ratio, can readily induce apoptotic death in K562 cells.
      This was accompanied with classical DNA oligonucleosomal fragmentation, an
      unexpected finding given the reported lack of such fragmentation when apoptosis
      is induced in K562 by chemical agents, after downregulation of BCR-ABL. Apoptosis
      was assessed by several means: morphological studies, 125I-DNA versus 51Cr
      release, DNA agarose gel electrophoresis, and results were always concordant,
      with a delayed kinetics for DNA oligonucleosomal fragmentation. Similar data were
      obtained with a pluripotent human hematopoietic cell line, UT-7, infected with a
      defective amphotropic p210 BCR-ABL retrovirus. The BCR-ABL expressing subclone UT
      7/9, while being no longer sensitive to cytotoxic drugs or to tumor necrosis
      factor, a lytic mediator to which UT-7 cells are sensitive, underwent apoptotic
      death when exposed to LAK effector cells to the same degree as the parental UT-7
      line. With these targets, DNA oligonucleosomal fragmentation occurred
      concomitantly with isotope release. Results obtained with several inhibitors of
      exocytosis strongly suggest that cytotoxic granules mediate NK and LAK cell
      induced apoptotic death. In conclusion, NK and LAK cell-induced apoptotic
      signals, unlike those activated by chemotherapeutic agents, are unaffected by the
      antiapoptotic action of BCR-ABL. This unique property may support the observed
      curative effect of allogeneic bone marrow transplantation in CML.

PMID- 8562938
TI  - The human homologue of rat NG2, a chondroitin sulfate proteoglycan, is not
      expressed on the cell surface of normal hematopoietic cells but is expressed by
      acute myeloid leukemia blasts from poor-prognosis patients with abnormalities of
      chromosome band 11q23.
AB  - In our efforts to produce monoclonal antibodies that recognize cell-surface
      antigens expressed by hematopoietic precursor and stromal cells, we generated a
      monoclonal antibody, 7.1, which recognizes a 220- to 240-kD cell-surface protein
      whose N-terminal amino acid sequence is identical to the rat NG2 chondroitin
      sulfate proteoglycan molecule. This chondroitin sulfate proteoglycan, previously
      reported to be expressed by human melanoma cells, was not found to be expressed
      by normal hematopoietic cells, nor was it expressed on the cell surface of cell
      lines of hematopoietic origin including cell lines with 11q23 abnormalities. It
      was found on the cell surface of acute myeloid leukemia (AML) blasts and cell
      lines derived from nonhematopoietic tissues. Samples of leukemic marrow from 166
      children with AML enrolled on Childrens Cancer Group protocol 213 were evaluated
      for cell-surface expression of this proteoglycan molecule. In 18 of 166 (11%)
      patient samples, greater than 25% of leukemic blasts expressed the NG2 molecule.
      These 18 patients had a poorer outcome with respect to survival (P = .002) and
      event-free survival (P = .035) with an actuarial survival at 4 years of 16.7%.
      Blast cell expression of the NG2 molecule was strongly associated with French
      American-British M5 morphology (P < .0001) and abnormalities in chromosome band
      11q23, site of the MLL gene. These results show that the NG2 molecule is
      expressed by malignant hematopoietic cells that have abnormalities in chromosome
      band 11q23, suggesting that antibody 7.1 may be useful in the rapid
      identification of this group of poor-prognosis patients.

PMID- 8562939
TI  - Human homologue of the rat chondroitin sulfate proteoglycan, NG2, detected by
      monoclonal antibody 7.1, identifies childhood acute lymphoblastic leukemias with
      t(4;11)(q21;q23) or t(11;19)(q23;p13) and MLL gene rearrangements.
AB  - Monoclonal antibody 7.1, which recognizes the chondroitin sulfate proteoglycan
      molecule NG2, was used to screen prospectively blast cells from 104 consecutive
      children at initial presentation with acute lymphoblastic leukemia (ALL).
      Reactivity with this antibody was found in 9 cases (8.6%), of whom 5 had a
      t(4;11)(q21;q23) and 4 had a t(11;19)(p13;q23). None of the NG2- cases had either
      translocation. Southern blot analysis disclosed MLL gene rearrangement in only
      the 9 cases with 7.1 reactivity plus the t(4;11)(q21;q23) or t(11;19)(q23;p13)
      translocation. MLL gene rearrangements were not detected in 89 patient leukemic
      samples that did not express NG2, including 7 patients with del(11)(q23) or
      inv(11)(p13q23). As expected from the association with t(4;11) and t(11;19), NG2+
      cases were significantly more likely to be infants, to have hyperleukocytosis and
      central nervous system involvement, to be CD10-, and to express myeloid
      associated antigens CD15 and CD65. Despite short follow-up duration, 3 of the
      NG2+ cases have relapsed while the other 101 patients remain in remission. Thus,
      blast cell surface expression of NG2 is useful for identifying patients with ALL
      having t(4;11) or t(11;19) translocations that are associated with poor
      prognosis, especially in the infant age group.

PMID- 8562940
TI  - Clinical relevance of BCL-2 overexpression in childhood acute lymphoblastic
      leukemia.
AB  - Enforced BCL-2 gene expression in leukemic cell lines suppresses apoptosis and
      confers resistance to anticancer drugs, but the clinical significance of
      increased BCL-2 protein levels in acute lymphoblastic leukemia (ALL) is unknown.
      Among 52 children with newly diagnosed ALL, BCL-2 expression in leukemic
      lymphoblasts ranged widely, from 4,464 to 59,753 molecules of equivalent soluble
      fluorochrome per cell (MESF), as determined by flow cytometry. The mean (+/- SD)
      level of MESF in 43 cases of B-lineage ALL (19,410 +/- 11,834) was higher than
      that detected in CD10+ B-lymphoid progenitors from normal bone marrow (450 +/-
      314; P < .001), and CD19+ peripheral blood B lymphocytes (7,617 +/- 1,731; P =
      .02). Levels of BCL-2 in T-ALL cases (17,909 +/- 18,691) were also generally
      higher than those found in normal CD1a+ thymocytes (1,762 +/- 670), or in
      peripheral blood T lymphocytes (9,687 +/- 3,019). Although higher levels of BCL-2
      corresponded to higher leukemic cell recoveries after culture in serum-free
      medium, they did not correlate with higher cell recoveries after culture on
      stromal layers, or with in vitro resistance to vincristine, dexamethasone, 6
      thioguanine, cytarabine, teniposide, daunorubicin or methotrexate. BCL-2 protein
      levels did not correlate with presenting clinical features. Unexpectedly,
      however, lower-than-median MESF values were significantly associated with the
      presence of chromosomal translocations (P = .010). Notably, all six cases with
      the Philadelphia chromosome, a known high-risk feature, had low levels of BCL-2
      expression (P = .022). Higher levels of BCL-2 were not associated with poorer
      responses to therapy among 33 uniformly treated patients, and were not observed
      in three patients studied at relapse. In conclusion, increased BCL-2 expression
      in childhood ALL appears to enhance the ability of lymphoblasts to survive
      without essential trophic factors, and is inversely related to the presence of
      chromosomal translocations. However, it does not reflect increased disease
      aggressiveness or resistance to chemotherapy.

PMID- 8562941
TI  - Transforming growth factor-beta 1 cooperates with anti-immunoglobulin for the
      induction of apoptosis in group I (biopsy-like) Burkitt lymphoma cell lines.
AB  - Group I Burkitt lymphoma (BL) cell lines, which retain the original biopsy
      phenotype, have been shown to enter apoptosis in response to a number of external
      stimuli including serum deprivation, thermal shock, addition of calcium
      ionophore, and ligation of surface immunoglobulin (Ig) by antibody. Transforming
      growth factor-beta 1 (TGF beta 1) is known to cause growth arrest in BL lines.
      Here we show that while it is by itself capable of promoting some degree of
      apoptosis in group IBL cells, TGF beta 1 cooperates with anti-immunoglobulin to
      this end. Trimeric soluble recombinant human CD40 ligand (sCD40L) was able to
      inhibit apoptosis induced by the combination of agonists to some degree, but such
      rescue proved to be short-lived. Both TGF beta 1 and anti-Ig individually caused
      BL cells to undergo growth arrest at the G1 phase of cell cycle before their
      entry into apoptosis: the consequence of sCD40L addition was to maintain the
      cells in cycle for longer. No induction of the apoptosis-protecting gene, bcl-2,
      occurred in the presence of sCD40L. These findings are discussed, particularly
      highlighting the relationship existing between survival and the cell cycle. The
      strong cooperative effects observed between anti-Ig and TGF beta 1 in promoting
      apoptosis and the inability of CD40 to signal for long-term rescue raise the
      potential for a novel therapeutic attack on B-cell lymphoma.

PMID- 8562942
TI  - High incidence of potential p53 inactivation in poor outcome childhood acute
      lymphoblastic leukemia at diagnosis.
AB  - Previous studies have indicated that p53 gene mutations were an uncommon event in
      acute lymphoblastic leukemia (ALL) in children. In one series of 330 patients,
      p53 mutations were seen in fewer than 3%. We analyzed bone marrow mononuclear
      cells derived from 10 children with ALL at diagnosis who subsequently failed to
      achieve a complete remission or who developed relapse within 6 months of
      attaining complete remission for p53 gene mutations and mdm-2 overexpression. We
      found that three children had p53 gene mutations, and four overexpressed mdm-2.
      Also, experiments comparing relative levels of mdm-2 RNA and protein in these
      patients demonstrated that mdm-2 overexpression can occur at the transcriptional
      and posttranscriptional level in primary leukemic cells. Although we were unable
      to link Waf-1 RNA expression with p53 status in childhood ALL, our data show
      potential p53 inactivation by multiple mechanisms in a large percentage of these
      patients and demonstrate that these alterations can be detected at diagnosis.
      Inactivation of the p53 pathway may, therefore, be important in children with ALL
      who fail to respond to treatment and may be useful for the early identification
      of children requiring alternative therapies.

PMID- 8562943
TI  - Leukemia-associated changes identified by quantitative flow cytometry. IV. CD34
      overexpression in acute myelogenous leukemia M2 with t(8;21).
AB  - During the immunodiagnosis of 517 cases of acute myelogenous leukemia (AML)
      entered into the Medical Research Council (MRC) AML 10 trials, we have observed
      the CD34 precursor cell antigen more frequently in AML of M2 morphology,
      especially in the 84% of cases with the t(8;21) chromosomal translocation, than
      in any other French-American-British classification group. CD34 expression was
      then quantified (using QIFI and Quantum Simply Cellular beads [Flow Cytometry
      Standards, Research Triangle Park, NC] and CD34+ standard cells). When CD34
      antibody-binding capacity (ABC) of normal bone marrow (BM) precursors and
      leukemic blasts was compared, it was shown that AML M2 cases with t(8;21) not
      only had the highest percentages of CD34+ blasts, but in > 80% of CD34+ cases the
      individual blasts expressed higher than normal levels of CD34 antigen (> 60 x
      10(3) ABC per cell). In addition, in 73% of this group CD34 antigen was
      overexpressed in an asynchronous combination with cytoplasmic myeloperoxidase
      (MPO). Other signs of asynchrony included high CD34 expression with CD15 and/or
      CD56, as well as aberrant combinations of CD13 with terminal deoxynucleotidyl
      transferase (TdT) and CD19. These findings demonstrate that asynchrony is
      identifiable in virtually every case of AML with t(8;21), although it does not
      always involve the same antigens. M2 cases with t(8;21), mostly CD34+, had a 100%
      remission rate and 71% 5-year survival rate; other patients with CD34+ or CD34-
      AML showed 69% and 84% remission rates and 31% and 36% 5-year survival rates,
      respectively. Consequently, individual markers such as CD34 should be interpreted
      in relation to other features such as chromosomal changes. These simple methods,
      which are well suited to quantify the expression of ligands, are a useful
      contribution to diagnosis: 60% to 65% of M2 cases with t(8;21) are rapidly
      identified by CD34 overexpression alone. This aberration, together with the other
      signs of asynchrony seen at presentation, can be used to search for residual
      leukemia after therapy.

PMID- 8562945
TI  - Detection of altered membrane phospholipid asymmetry in subpopulations of human
      red blood cells using fluorescently labeled annexin V.
AB  - The phospholipids of the human red cell are distributed asymmetrically in the
      bilayer of the red cell membrane. In certain pathologic states, such as sickle
      cell anemia, phospholipid asymmetry is altered. Although several methods can be
      used to measure phospholipid organization, small organizational changes have been
      very difficult to assess. Moreover, these methods fail to identify subpopulations
      of cells that have lost their normal phospholipid asymmetry. Using fluorescently
      labeled annexin V in flow cytometry and fluorescent microscopy, we were able to
      identify and quantify red cells that had lost their phospholipid asymmetry in
      populations as small as 1 million cells. Moreover, loss of phospholipid
      organization in subpopulations as small as 0.1% of the total population could be
      identified, and individual cells could be studied by fluorescent microscopy. An
      excellent correlation was found between fluorescence-activated cell sorter (FACS)
      analysis results using annexin V to detect red cells with phosphatidylserine (PS)
      on their surface and a PS-requiring prothrombinase assay using similar red cells.
      Cells that bound fluorescein isothiocyanate (FITC)-labeled annexin V could be
      isolated from the population using magnetic beads covered with an anti-FITC
      antibody. Evaluation of blood samples from patients with sickle cell anemia under
      oxygenated conditions demonstrated the presence of subpopulations of cells that
      had lost phospholipid asymmetry. While only a few red cells were labeled in
      normal control samples (0.21% +/- 0.12%, n = 8), significantly increased (P <
      .001) annexin V labeling was observed in samples from patients with sickle cell
      anemia (2.18% +/- 1.21%, n = 13). We conclude that loss of phospholipid asymmetry
      may occur in small subpopulations of red cells and that fluorescently labeled
      annexin V can be used to quantify and isolate these cells.

PMID- 8562944
TI  - Moderate reduction of beta-globin gene transcript by a novel mutation in the 5'
      untranslated region: a study of its interaction with other genotypes in two
      families.
AB  - We have identified two individuals of Greek Cypriot origin with thalassemia
      intermedia. Molecular analysis has shown that each individual is a compound
      heterozygote for a previously described beta zero thalassemia allele and a novel
      mutation, C-->G in position +33, in the 5' untranslated region of the beta globin
      gene. In both families the beta +33 allele is associated with the same beta
      haplotype (-++- ) suggesting that it is likely to be of a single origin, beta
      cDNAs from normal and mutant beta alleles were isolated from peripheral blood
      reticulocytes using the technique of reverse transcription-polymerase chain
      reaction. Because the beta +33 (C-->G) mutation creates a cutting site for the
      restriction enzyme NlalV, we could demonstrate by differential restriction
      analysis that the beta gene with +33 mutation showed 25% to 35% residual activity
      compared with normal. The additive effect of this moderate deficit in beta globin
      production with the beta zero thalassemia mutation would explain the clinical
      phenotypes observed in the two probands. In contrast, two siblings of one proband
      who were also compound heterozygotes for the same beta thalassemia mutations, as
      well as heterozygotes for a nondeletional alpha thalassemia variant, and two
      other compound heterozygotes for the beta +33 and a beta+ thalassemia allele were
      completely asymptomatic. Individuals heterozygous for the beta +33 C-G mutation
      alone are clinically and hematologically silent, with normal red blood cell
      indices and normal levels of hemoglobin (Hb) A2. A direct relationship between
      genotypic and phenotypic severity is clearly demonstrated in these cases with
      obvious implications for prenatal diagnosis.

PMID- 8562946
TI  - Combination therapy of erythropoietin, hydroxyurea, and clotrimazole in a beta
      thalassemic mouse: a model for human therapy.
AB  - beta thalassemia (beta thal) in DBA/2J mice is a consequence of the spontaneous
      and complete deletion of the beta major globin gene. Homozygous beta thal mice
      have clinical and biological features similar to those observed in human beta
      thal intermedia. Erythrocytes in human beta thal are characterized by a relative
      cell dehydration and reduced K+ content. The role of this erythrocyte dehydration
      in the reduced erythrocyte survival, which typifies the disease, has not
      previously been evaluated. We examined for 1 month the effects on the anemia and
      the erythrocyte characteristics of beta thal mice of daily treatment with either
      clotrimazole (CLT), an inhibitor of red blood cell (RBC) dehydration via the
      Gardos channel, or human recombinant erythropoietin (r-HuEPO), or hydroxyurea
      (HU). The use of either r-HuEPO or HU induced a significant increase in
      hemoglobin (Hb), hematocrit (Hct), erythrocyte K+ and a decrease in percent
      reticulocytes, suggesting improved erythrocyte survival. CLT alone decreased only
      mean corpuscular hemoglobin concentration (MCHC) and cell density and increased
      cell K+. Thus, though the Gardos channel plays a major role in cell dehydration
      of murine beta thal erythrocyte survival. Combination therapy with r-HuEPO plus
      HU produced no incremental benefit beyond those of single drug therapy. However,
      addition of CLT to r-HuEPO, to HU, or to combined r-HuEPO plus HU led to
      statistically significant increase in Hb, Hct, and erythrocyte K+ compared with
      any of the regimens without CLT. These results suggest that CLT not only inhibits
      erythrocyte dehydration, but also potentiates the erythropoietic and cellular
      survival responses to r-HuEPO and HU.

PMID- 8562947
TI  - Graft-versus-myeloma effect: proof of principle.
AB  - The presence of a graft-versus-tumor effect has been well established in leukemia
      but not in multiple myeloma. A 40-year-old patient with myeloma refractory to
      standard chemotherapy and autologous transplantation received a matched unrelated
      T-cell-depleted transplant after conditioning with fractionated total-body
      irradiation, thiotepa, and cyclophosphamide. This procedure resulted in a
      transient and incomplete response with evidence of rapidly progressive disease
      within 2.5 months posttransplantation. The patient then received a small number
      of donor peripheral blood (PB) mononuclear cells (CD3 cells 1.2 x 10(6)/kg)
      without any further cytotoxic therapy. A complete remission was attained, lasting
      now for more than 14 months. The procedure was associated with severe acute and
      subsequently limited chronic graft-versus-host disease (GVHD). This report
      provides the first direct evidence of a graft-versus-myeloma effect after
      allogenic transplantation.

PMID- 8562948
TI  - Rapid response to cyclosporine therapy and sustained remission in large granular
      lymphocyte leukemia.

PMID- 8562949
TI  - Neutrophil serine proteases are most probably involved in the release of CD43
      (leukosialin, sialophorin) from the neutrophil membrane during cell activation.

PMID- 8562950
TI  - Steroid-free chemotherapy decreases the risk of hepatitis flare-up in hepatitis B
      virus carriers with non-Hodgkin's lymphoma.

PMID- 8562951
TI  - Expression of Epstein-Barr virus-encoded latent membrane protein 1 in nonendemic
      Burkitt's lymphomas.

PMID- 8562952
TI  - Soluble cytokine receptors.

PMID- 8562953
TI  - Suppression of apoptosis during cytokine deprivation of 32D cells is not
      sufficient to induce complete granulocytic differentiation.
AB  - The role of cytokines in the control of hematopoietic cell differentiation
      remains controversial. Two general models for the cytokine control of
      hematopoietic differentiation have been proposed. In the stochastic model,
      cytokines provide proliferative and survival signals to the differentiating
      hematopoietic cell, but they do not provide specific lineage commitment signals.
      In the instructive model, cytokines transmit specific signals to multipotent
      hematopoietic cells, thereby directing lineage commitment. To distinguish between
      these two models with respect to granulocyte colony-stimulating factor (G-CSF)
      and granulocytic differentiation, we used the 32Dcl3 cell line, which is capable
      of differentiating into granulocytes in response to G-CSF, 32D cells transfected
      with either bcl-2 or bcl-XL showed prolonged survival in medium containing no
      cytokine supplement. Cells surviving in these cultures developed the segmented
      nuclei characteristic of mature neutrophils. However, no induction of
      myeloperoxidase activity or increase in cathepsin G transcripts were detected.
      These data support a hybrid model for the role of G-CSF in granulocytic
      differentiation; although some features of granulocytic differentiation, namely
      nuclear segmentation, do not require G-CSF and appear therefore to be
      preprogrammed in 32D cells, the complete maturation of these cells to
      granulocytes appears to be dependent on G-CSF.

PMID- 8562954
TI  - p59fyn-p125FAK cooperation in development of CD4+CD8+ thymocytes.
AB  - p59fyn is an Src family nonreceptor tyrosine kinase that has been suggested to
      play an important role in T-cell development and function. p125FAK is a unique
      nonreceptor tyrosine kinase and has been known to respond to integrin
      extracellular matrix interactions. To examine their roles in thymocytes,
      heterozygous fak mutation was introduced into homozygous Fyn deficiency. The
      double mutation, but neither Fyn deficiency nor FAK heterozygosity alone,
      displayed impaired development of CD4+CD8+ thymocytes with atrophy of the thymic
      cortex, suggesting a unique cooperation between p59fyn and p125FAK in CD4+CD8+ T
      cell development.

PMID- 8562955
TI  - Fas ligation induces apoptosis and Jun kinase activation independently of CD45
      and Lck in human T cells.
AB  - Stimulation through the Fas/APO-1 receptor results in apoptosis through an
      incompletely characterized signaling pathway. More is known regarding signal
      transduction events that occur after ligation of the T-cell antigen receptor
      (TCR). It has been shown that TCR stimulation requires both the membrane tyrosine
      phosphatase, CD45, and the Src-family kinase, Lck, to result in cellular
      activation. Although prior studies suggest a role for protein tyrosine kinases
      and phosphatases in Fas signaling, we report here that Fas ligation induces
      apoptosis in T cells deficient in either CD45 or Lck. Further, in normal and CD45
      or Lck-deficient cell lines, Fas stimulation results in activation of Jun kinase
      (JNK), a proposed mediator of stress activation pathways. Previous studies have
      also demonstrated a role for endogenous ceramide release in Fas-mediated
      apoptosis. We show that stimulation with a synthetic ceramide analog results in
      JNK activation as well as apoptosis, suggesting ceramide release occurs proximal
      to JNK activation in Fas signaling. Our data suggest that although CD45 and Lck
      are not required for Fas signaling, JNK activation may play an important role
      transducing distal signals that lead to apoptosis after Fas ligation.

PMID- 8562956
TI  - Deletion variants within the NF-kappa B activation domain of the LMP1 oncogene
      prevail in acquired immunodeficiency syndrome-related large cell lymphomas and
      human immunodeficiency virus-negative atypical lymphoproliferations.
AB  - This sequencing study of 17 acquired immunodeficiency syndrome-related lymphomas
      (9 primary brain, 8 systemic) and 8 human immunodeficiency virus-negative
      atypical lymphoproliferations expressing large amounts of the latent membrane
      protein 1 (LMP1) of Epstein-Barr virus was performed to characterize the carboxy
      terminal NF-kappa B activation domain of LMP1 at the molecular level in an
      immunocompromised host. In-frame deletions within the NF-kappa B activation
      domain were identified in all but 2 primary brain lymphomas, 4 systemic
      lymphomas, and 4 atypical lymphoproliferations, ie, in 60% of cases. In addition,
      non silent point mutations (range 1 to 5, mean 3.3) were detected in all cases.
      Although all changes occurred within the first 100 nucleotides of the carboxy
      terminal NF-kappa B activation domain--a critical sequence for the protein half
      life--not a single point mutation was found in the remaining 62 nucleotides,
      necessary for malignant transformation. Such a clustering of nonrandom sequence
      variations, associated with a high oncoprotein expression in immunocompromised
      hosts, suggests that this part of the LMP1 oncogene behaves as a hypervariable
      region with natural selection of growth-promoting variants through prolongation
      of the protein half-life.

PMID- 8562958
TI  - Hydroxyurea increases hemoglobin F levels and improves the effectiveness of
      erythropoiesis in beta-thalassemia/hemoglobin E disease.
AB  - Hydroxyurea (HU) is one of several agents that have been shown to enhance
      hemoglobin (Hb) F levels in patients with sickle cell disease and may be useful
      as a therapy for beta-globinopathies. However, limited information exists on the
      effects of HU in patients with thalassemia. Accordingly, we examined the
      hematologic effects of orally administered HU in 13 patients with beta
      thalassemia/Hb E, including four patients who had been splenectomized. These
      patients were treated with escalating doses (final range, 10 to 20 mg/kg/d) for 5
      months and were observed in the outpatient hematology clinic every 2 to 4 weeks.
      Complete blood counts including reticulocyte counts, amounts of Hb E and Hb F, G
      gamma:A gamma and alpha:non-alpha globin biosynthetic ratios were evaluated
      before and during treatment. Almost all patients responded with an average
      increase of 33% in Hb F levels, from a mean (+/- SD) of 42% +/- 11% to 56% +/- 8%
      (P < .0001), and a reciprocal decline in the percentage of Hb E from 59% +/- 9%
      to 49% +/- 8% (P < .001). Reticulocytosis was decreased from a mean (+/- SD) of
      18.0% +/- 15.6% to 11.7% +/- 9.1% (P < .05); there was also a slight (10%) but
      statistically significant increase in hemoglobin levels and an improved balance
      in alpha:non-alpha globin chains ratios. The side effects were minimal in most
      patients, although these patients tended to tolerate a lower dose of HU before
      significant myelosuppression than has been our previous experience in sickle cell
      disease. One splenectomized patient died of sepsis during the trial. We conclude
      that increased Hb F production in beta-thalassemia/Hb E patients, with an
      improvement in the alpha:non-alpha globin ratios and, probably, the effectiveness
      of erythropoiesis, can be achieved using HU. Longer trials of HU in this
      population, including at other doses and in combination with other agents, appear
      warranted.

PMID- 8562957
TI  - The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin
      retinoic acid receptor fusion.
AB  - We have studied an acute promyelocytic leukemia (APL) patient with a variant
      t(5;17)(q32;q12). This translocation fuses the gene for the nucleolar
      phosphoprotein nucleophosmin (NPM) to the retinoic acid receptor alpha (RARA).
      Two alternatively spliced transcripts are expressed, which differ in 129 bases
      immediately upstream of the RARA sequence. The NPM sequences contained in the
      shorter NPM-RAR cDNA are identical to the NPM sequences contained in the NPM-ALK
      fusion gene expressed in t(2;5) lymphomas. The RARA sequences are the same as the
      RARA sequences found in the PML-RAR and PLZF-RAR fusion seen in t(15;17) and
      t(11;17) APL, respectively. Both NPM-RAR transcripts fuse NPM and RARA sequence
      in the same reading frame, to generate translation products of 57 kD and 62 kD.
      Both NPM-RAR proteins are expressed in the patient's leukemic cells, along with
      wild-type RARA derived from the uninvolved allele. In transcriptional assays
      using a retinoic acid response element reporter construct, both NPM-RAR fusion
      proteins act as retinoic acid-dependent transcriptional activators. This case
      defines a third class of APL rearrangements, all of which generate fusion
      proteins of RARA.

PMID- 8562959
TI  - Treatment of cutaneous T-cell lymphoma with chimeric anti-CD4 monoclonal
      antibody.
AB  - Chimeric anti-CD4 monoclonal antibody was administered intravenously as a single
      dose to eight patients with mycosis fungoides. The dose was escalated throughout
      the study between patients groups, and individual patients received 50, 100, or
      200 mg per dose. Seven of eight patients responded to treatment with an average
      freedom from progression of 25 weeks (range, 6 to 52 weeks). The treatment was
      well tolerated, and there was no clinical evidence of immunosuppression.
      Following treatment, there was significant suppression of peripheral blood CD4
      counts in all patients for 1 to 22+ weeks. Only one patient made a very low titer
      human antichimeric antibody response. All but two patients made primary antibody
      and T-cell proliferative responses to a foreign antigen administered 24 hours
      after antibody infusion. However, there was generally marked, but temporary
      suppression of T-cell proliferative responses in vitro to phytohemagglutinin
      (PHA), tetanus toxoid, and normal donor lymphocytes. We conclude that at the dose
      levels studied, this antibody (1) had clinical efficacy against mycosis
      fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4)
      decreased T-cell proliferative responses in vitro, and (5) did not induce
      tolerance to a foreign antigen.

PMID- 8562960
TI  - Effects of granulocyte colony-stimulating factor on plasma cytokine and cytokine
      receptor levels and on the in vivo host response to endotoxin in healthy men.
AB  - We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on
      cytokine and cytokine receptor plasma levels and on the in vivo host response to
      Salmonella abortus equi endotoxin in healthy males. Twenty volunteers received
      0.8 ng/kg endotoxin and saline intravenously 1 week apart in randomized order.
      Twelve hours before both experiments, 10 of these subjects were pretreated with
      300 micrograms G-CSF subcutaneously. G-CSF itself increased granulocyte and
      monocyte counts and the plasma levels of tumor necrosis factor-alpha (TNF-alpha),
      soluble TNF receptors (sTNF-R) p55, and p75 and interleukin-1 receptor antagonist
      (IL-1ra). G-CSF did not influence plasma IL-1 beta and IL-6 levels. In the G-CSF
      pretreated subjects endotoxin-induced surges in rectal temperature and in the
      plasma levels of TNF-alpha plasma levels were about 50% increased, and surges in
      the plasma levels of both sTNF-Rs and IL-1ra were about twice as high as in the
      control group. Endotoxin-induced increases in IL-6, cortisol, and heart rate were
      not modified by G-CSF pretreatment. Endotoxin administration induced a transient
      50% reduction in leukocyte counts in the G-CSF-pretreated subjects that was not
      seen in the control group. We conclude that a single stand dose of G-CSF
      increases the plasma levels of cytokines and cytokine receptors and considerably
      modifies the host response of healthy humans to a low dose of endotoxin.

PMID- 8562961
TI  - Phase II trial of 2-chlorodeoxyadenosine for the treatment of cutaneous T-cell
      lymphoma.
AB  - We investigated the efficacy of 2-chlorodeoxyadenosine (2-CdA) therapy in
      patients with mycosis fungoides (MF) and the Sezary syndrome (SS). Between
      February 1991 and November 1993, 21 patients with relapsed or refractory MF/SS
      were treated with 2-CdA. 2-CdA was administered by continuous intravenous
      infusion at a dose of 0.1 mg/kg/d for 7 days initially (13 patients), but was
      subsequently reduced to 5 days (nine patients) due to hematologic toxicity. All
      patients had failed to respond to at least one prior treatment for MF/SS (median
      number of total prior therapies, five; median number of systemic prior therapies,
      three) and had an Eastern Cooperative Oncology Group performance status of two or
      better. Cycles were administered at 28-day intervals. Assessable patients
      received at least 5 days of 2-CdA. Fourteen patients received more than one cycle
      of 2-CdA. An overall response rate of 28% was achieved. Three patients (14%) had
      a complete response with a median duration of 4.5 months (range, 2.5 to 16).
      Three (14%) had a partial response with a median duration of 2 months (range, 2
      to 4). Fifteen patients (72%) had no response. The most significant toxicities
      encountered were bone marrow suppression (62% of patients) and infectious
      complications (62% of patients). Thirty-eight percent of patients experienced no
      toxicity from 2-CdA. 2-CdA has activity as a single agent in patients with
      previously treated relapsed MF/SS. Studies in less heavily pretreated individuals
      with 2-CdA alone or in combination will be undertaken.

PMID- 8562962
TI  - Role of different hematologic variables in defining the risk of malignant
      transformation in monoclonal gammopathy.
AB  - The presenting clinico-hematologic features of 386 patients with nonmyelomatous
      monoclonal gammopathy (MG) were correlated with the frequency of malignant
      transformation to evaluate the most important variables conditioning its
      evolution into multiple myeloma (MM) or Waldenstrom macroglobulinemia (WM). Most
      of the patients (335) had monoclonal gammopathy of undetermined significance
      (MGUS: 39 IgA, 242 IgG, 54 IgM): the remaining 51 patients (12 IgA, 39 IgG)
      fulfilled all of the MGUS diagnostic criteria (according to Durie) except that
      bone marrow plasma cell (BMPC) content was 10% to 30%, and so they were defined
      as having monoclonal gammopathy of borderline significance (MGBS). There were no
      significant differences between the MGUS and MGBS groups in terms of age, sex, or
      median follow-up. After a median follow-up of 70 and 53 months, respectively, 23
      of 335 MGUS and 19 of 51 MGBS patients had undergone a malignant evolution.
      Univariate analysis of the IgA and IgG patients showed that the cumulative
      probability of the disease evolving into MM correlated with diagnostic definition
      (MGBS v MGUS), BMPC content (> or = 10% v < 5% and < or = 5% v > 5%) and reduced
      serum polyclonal Ig. In the IgG cases, there was also a significant correlation
      with detectable Bence Jones proteinuria, serum monoclonal component (MC) levels
      and age at diagnosis (> 70 v < = or 55 years). In the IgG cases as a whole, the
      same variables remained in the Cox model where the BMPC percentage was considered
      after natural logarithmic transformation and the monoclonal component as g/dL
      value. The relative risks of developing MM are the following: 2.4 for each 1 g/dL
      increase of IgG, serum MC, 3.5 for detectable light chain proteinuria, 4.4 for
      the increase of 1 unit in log. BMPC percentage, 6.1 for age > 70, 3.6 and 13.1
      for a reduction in one or two polyclonal Ig. In conclusion, our study allows the
      identification of a particular subset of MGUS patients (MC < = or 1.5 g/dL, BMPC
      < 5%, no reduction in polyclonal Ig and no detectable light chain proteinuria) at
      very low-risk of evolution, who can be considered as having benign monoclonal
      gammopathies. We also describe a previously undefined group of MG patients (with
      monoclonal gammopathy of borderline significance) who are at high-risk of
      malignant evolution. These findings could have a considerable impact on the
      cost/benefit ratio of monitoring programs in these patients.

PMID- 8562963
TI  - Human immunodeficiency virus infection of bone marrow endothelium reduces
      induction of stromal hematopoietic growth factors.
AB  - The majority of human immunodeficiency virus (HIV)-seropositive patients develop
      bone marrow abnormalities associated with hematopoietic malfunction during the
      progression of disease. One important manifestation of HIV-associated
      hematopoietic dysfunction is that after myelosuppression, bone marrow recovery, a
      process known to be mediated in part by the production of stromal cell-derived
      hematopoietic growth factors, is impaired. We sought to test the hypothesis that
      bone marrow stromal cells are infected by HIV-1 in vivo and that production of
      certain stromal cell-derived hematopoietic growth factors is deficient as a
      consequence. In this report, we demonstrate that bone marrow microvascular
      endothelial cells (MVEC), a key element of the stroma, are the predominant cells
      infected by HIV (5% to 20%) in bone marrow stromal cultures obtained from 11
      consecutive HIV-seropositive patients. Although HIV-infected stromal cultures
      enriched for MVEC constitutively express normal levels of interleukin (IL)-4, IL
      6, granulocyte (G)-colony-stimulating factor (CSF), granulocyte-macrophage (GM)
      CSF, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta,
      and Steel factor, IL-1 alpha-induced release of IL-6 and G-CSF is significantly
      reduced in these cultures. These observations suggest that HIV infection of bone
      marrow MVEC reduces the capacity of hematopoietic stroma to respond to regulatory
      signals that normally augment blood cell production during periods of increased
      demand.

PMID- 8562964
TI  - Isolation of the full-length murine erythropoietin receptor using a baculovirus
      expression system.
AB  - The full-length murine erythropoietin receptor was expressed in Spodoptera
      frugiperda (Sf9) cells using a recombinant baculovirus vector. Erythropoietin
      receptor protein production was maximal 48 hours after infection, as determined
      by metabolic labeling and immunoblotting; receptor protein varied in molecular
      mass from 62 to 76 kD. Erythropoietin receptors produced in Sf9 cells could be
      solubilized using CHAPS in a form capable of binding erythropoietin, and the
      solubilized receptor bound to immobilized Concanavalin A (Con A) and wheat germ
      agglutinin, as well as to immobilized recombinant human erythropoietin. Analysis
      of the distribution of erythropoietin receptors in Sf9 plasma membrane and
      cytosol fractions using lectin affinity chromatography revealed that membrane
      bound receptor had a higher apparent molecular mass and contained the bulk of
      receptors that bound to wheat germ agglutinin. The receptor was purified by
      sequential affinity chromatography on Con A-Sepharose and immobilized
      erythropoietin. Erythropoietin receptors expressed in Sf9 cells were inserted
      into the plasma membrane in the correct orientation, bound 125I-erythropoietin
      with a single affinity (kD, 330 pmol/L), and were internalized after ligand
      binding. However, kD varied inversely with the number of cell surface receptors.
      Solubilized erythropoietin receptors in whole-cell lysates and isolated plasma
      membranes exhibited high-affinity binding, with kD values of 92 and 57 pmol/L,
      respectively. Erythropoietin bound to the surface of infected Sf9 cells could be
      cross-linked to two proteins with molecular masses of 90 and 65 kD using the
      homobifunctional cross-linker, disuccinimidyl suberate (DSS). Similar results
      were obtained with solubilized receptors in whole-cell lysates, and both proteins
      could be immunoprecipitated by an antiserum to the erythropoietin receptor
      carboxyl-terminal domain.

PMID- 8562965
TI  - Fanconi anemia genes act to suppress a cross-linker-inducible p53-independent
      apoptosis pathway in lymphoblastoid cell lines.
AB  - Hypersensitivity to cross-linking agents such as mitomycin C (MMC) is
      characteristic of cells from patients suffering from the inherited bone marrow
      failure syndrome. Fanconi anemia (FA). Here, we link MMC hypersensitivity of
      Epstein-Barr virus (EBV)-immortalized FA lymphoblasts to a high susceptibility
      for apoptosis and p53 activation. In MMC-treated FA cells belonging to
      complementation group C (FA-C), apoptosis followed cell cycle arrest in the G2
      phase. In stably transfected FA-C cells, plasmid-driven expression of the wild
      type cytoplasmic FAC protein relieved MMC-dependent G2 arrest and suppressed p53
      activation. However, in both FA and non-FA lymphoblasts, p53 seemed not to be
      instrumental in the induction of MMC-dependent apoptosis, since overexpression of
      a dominant-negative p53 mutant failed to affect cell survival. In addition, no
      differences in the level of Bcl-2 expression, an inhibitor of apoptosis, were
      detected between FA and non-FA cells either in the absence or presence of MMC.
      Our findings suggest that FAC and the other putative FA gene products may
      function in a yet to be identified p53-independent apoptosis pathway.

PMID- 8562966
TI  - Phenotypic, molecular, and functional characterization of human peripheral blood
      CD34+/THY1+ cells.
AB  - A subset of mobilized CD34+ cells present in patient aphereses expresses Thy1
      (CDw90). This population contains most long-term culture initiating cells, as
      assayed with a murine stromal cell line. It also contains a significant
      proportion of colony-forming unit granulocyte macrophage, but very few burst
      forming unit erythroid. The limited differentiation towards the erythroid lineage
      is further confirmed by the absence of GATA-1 mRNA in the CD34+/Thy1+ subset, and
      by the low level of c-kit expression. The CD34+/Thy1+ subset appears
      phenotypically and functionally heterogeneous, a finding consistent with its high
      representation, compared to phenotypes such as CD34+/CD38-. Therefore, while at
      least some of CD34+/Thy1+ cells may be infectable by retroviral vectors, as shown
      by the presence of a transcript for the receptor for murine amphotropic
      retroviruses, the use of this selection strategy to specifically target human
      stem cells appears questionable.

PMID- 8562967
TI  - Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2
      receptor gamma chain.
AB  - The interleukin-2 (IL-2) receptor gamma chain is indispensable for IL-2-, IL-4-,
      IL-7-, IL-9-, and IL-15-mediated signaling. Mutations of the human gamma chain
      cause the X-linked severe combined immunodeficiency (XSCID), showing that T and
      natural killer cells absolutely require the gamma chain for their development in
      humans. To elucidate the roles of the gamma chain in hematopoiesis, we have
      generated mice, by gene targeting, that express a form of the gamma chain lacking
      the cytoplasmic region. Male mice carrying the truncated gamma-chain mutant,
      which mimics mutations in patients with XSCID, showed a decrease in the number of
      lymphocytes and an increase in monocytes; the number of T cells was profoundly
      reduced and no natural killer cells were detected, which is similar to the
      characteristic of human XSCID. Unlike human XSCID, the levels of B cells were
      also reduced. In spite of the severe decrease in CD45R+/sIgM+ B cells, the level
      of IgM in serum of the 8-week-old mutant mice was higher than that of control
      littermates. Interestingly, the stem cell population with surface phenotypes of
      CD34, c-kit, and Sca-1 was significantly increased. Furthermore, the colony
      forming assay showed that the mutant mice had 15-fold higher numbers of
      hematopoietic progenitor cells in the spleen as compared with that of controls.
      These results indicate that functional loss of the gamma chain causes significant
      effects on the immunological system in mice.

PMID- 8562968
TI  - Phorbol ester enhances integrin alpha IIb beta 3-dependent adhesion of human
      erythroleukemic cells to activation-dependent monoclonal antibodies.
AB  - Following platelet stimulation by agonists, integrin-alpha IIb beta 3 (or
      glycoprotein IIb-IIIa) is converted to an activated state that can bind soluble
      fibrinogen and mediate platelet aggregation. However, little is known about
      modulation of alpha IIb beta 3 in cell lines. In the present study, we show that
      agonist stimulation modulates alpha IIb beta 3-dependent adhesive properties of a
      human erythroleukemic (HEL) cell line. Brief treatment with phorbol 12-myristate
      13-acetate (PMA) caused a significant increase in HEL cell adhesion to monoclonal
      antibodies (MoAbs) specific for activated alpha IIb beta 3 (PAC1 or pl-55). This
      adhesion was inhibited by blocking MoAbs or peptides specific for alpha IIb beta
      3, but not by anti-Fc gamma receptor-specific MoAb. Similarly, PMA enhanced HEL
      cell adhesion to immobilized fibrinogen by 10-fold. However, the activation
      dependent ligands in solution (ie, PAC1, pl-55, or fibrinogen) did not inhibit
      the enhanced HEL cell adhesion to immobilized MoAbs PAC1 or pl-55 after PMA
      treatment. Thus, PMA may increase alpha IIb beta 3-dependent adhesion to
      immobilized activation-dependent antibodies and fibrinogen by increasing the
      local concentration of alpha IIb beta 3 to participate in low-affinity
      interactions, resulting in an increased avidity, changing the affinity state of
      alpha IIb beta 3, or both.

PMID- 8562969
TI  - Differential effects of nitric oxide on erythroid and myeloid colony growth from
      CD34+ human bone marrow cells.
AB  - Nitric oxide (NO) is a reactive molecule with numerous physiologic and
      pathophysiologic roles affecting the nervous, cardiovascular, and immune systems.
      In previous work, we have demonstrated that NO inhibits the growth and induces
      the monocytic differentiation of cells of the HL-60 cell line. We have also
      demonstrated that NO inhibits the growth of acute nonlymphocytic leukemia cells
      freshly isolated from untreated patients and increases monocytic differentiation
      antigens in some. In the present work, we studied the effect of NO on the growth
      and differentiation of normal human bone marrow cells in vitro. Mononuclear cells
      isolated from human bone marrow were cultured in semisolid media and treated with
      the NO-donating agents sodium nitroprusside (SNP) or S-nitroso-acetyl
      penicillamine (SNAP) (0.25 to 1 mmol/L). Both agents decreased colony-forming
      unit-erythroid (CFU-E) and colony-forming unit-granulocyte macrophage (CFU-GM)
      formation by 34% to 100%. When CD34+ cells were examined, we noted that these
      cells responded to SNP and SNAP differently than did the mononuclear cells. At a
      concentration range of 0.25 to 1 mmol/L, SNP inhibited the growth of CFU-E by 30%
      to 75%. However, at the same concentration range, SNP increased the number of CFU
      GM by up to 94%. At concentrations of 0.25 to 1 mmol/L, SNAP inhibited the growth
      of CFU-E by 33% to 100%. At a concentration of 0.25 mmol/L, SNAP did not affect
      CFU-GM. At higher concentrations, SNAP inhibited the growth of CFU-GM. Although
      SNP increased intracellular levels of cGMP in bone marrow cells, increasing cGMP
      in cells by addition of 8-Br-cGMP (a membrane permeable cGMP analogue) did not
      reproduce the observed NO effects on bone marrow colonies. These results
      demonstrate that NO can influence the growth and differentiation of normal human
      bone marrow cells. NO (generated in the bone marrow microenvironment) may play an
      important role modulating the growth and differentiation of bone marrow cells in
      vivo.

PMID- 8562970
TI  - A1, a Bcl-2 family member, prolongs cell survival and permits myeloid
      differentiation.
AB  - A1, a bcl-2 family member, has been identified as a hematopoietic-specific, early
      inducible gene. In this study it is shown that stable transfection of A1 into an
      interleukin-3 (IL-3)-dependent myeloid precursor cell line, 32D c13, leads to a
      retardation of IL-3 withdrawal-induced cell death similar to that observed with
      transfection of bcl-2. However, unlike bcl-2. A1 expression permits the
      accumulation of differentiated myeloid cells both before and after IL-3
      withdrawal. Total cell accumulation, on the other hand, is considerably greater
      after IL-3 deprivation in the bcl-2 transfectant than in A1-expressing cells.
      Cells cotransfected with the two genes behave similarly to cells singly
      transfected with bcl-2, except that viability following IL-3 withdrawal is
      somewhat further enhanced. These results suggest that these two proteins have
      distinct roles that may be related to the divergent regulation of their
      expression during myeloid differentiation.

PMID- 8562971
TI  - Abundant expression of transcription factor GATA-2 in proliferating but not in
      differentiated mast cells in tissues of mice: demonstration by in situ
      hybridization.
AB  - Although GATA-binding transcription factors (GATA-1 and GATA-2) are strongly
      expressed in cultured mast cells (CMCs), their expression in mast cells within
      tissues has not been reported. We examined the expression of GATA-1 and GATA-2 in
      skin tissues of mice using Northern blot analysis and in situ hybridization. mRNA
      for GATA-2 but not for GATA-1 was expressed in skin mast cells of WB-+/+ embryos
      between days 15 and 17 postcoitum (pc). The expression was downregulated on and
      after day 18 pc. Skin mast cells did not express GATA-2 after birth either. When
      the number of skin mast cells was compared with the number of GATA-2 mRNA
      expressing cells, GATA-2 mRNA appeared to be expressed by mast cells only when
      the number was increasing. When the mRNA expression of high-affinity IgE receptor
      beta-subunit and mast cell carboxypeptidase A was used as differentiation
      markers, the expression of these mRNAs continued even after the downregulation of
      GATA-2 expression. To clarify the relationship of the proliferation and GATA-2
      expression, proliferating CMCs derived from WBB6F1-+/+ mice were transplanted
      into the peritoneal cavity of mast cell-deficient WBB6F1-W/Wv mice. The CMCs
      stopped both the proliferation and GATA-2 expression after the transplantation,
      suggesting the association of these two parameters in mast cells within tissues
      of mice.

PMID- 8562972
TI  - TPA-induced arrest of erythroid differentiation is coupled with downregulation of
      GATA-1 and upregulation of GATA-2 in an erythroid cell line SAM-1.
AB  - GATA-1 protein is thought to be a positive regulator of erythroid
      differentiation. However, ectopic expression of a conditional GATA-2/estrogen
      receptor chimera was shown to inhibit erythroid differentiation in a hormone
      dependent manner, suggesting the negative regulation of erythroid differentiation
      by GATA-2 protein. Accordingly, we reasoned that the quantitative balance of GATA
      1 and GATA-2 protein might affect erythroid differentiation. In this report, we
      performed specific and quantitative measurements of GATA-1 and GATA-2 protein in
      a new erythroid cell line, SAM-1, after treatment with 12-O-tetradecanoylphorbol
      13-acetate (TPA). On the basis of these measurements, we show that TPA-induced
      arrest of erythroid differentiation is coupled with the upregulation of GATA-2
      protein, as well as the downregulation of GATA-1 protein. Our results suggest
      that it is the precise quantitative balance of GATA-1 and GATA-2 protein that
      regulates erythroid differentiation.

PMID- 8562973
TI  - CD34 cell separation: from basic research to clinical applications.
AB  - Advances in the immunological identification of primitive haematopoietic cells
      have led to the development of various techniques for their characterisation and
      purification. The expression of the CD34 antigen by the stem cell compartment has
      been exploited for these purposes. Separation systems capable of isolating CD34+
      cells on a large scale are finding use in the clinic. Areas of interest overlap
      for both researchers and clinicians, and efforts to mobilise, characterise,
      purify and transplant these cells continue. Different CD34 purification systems
      are reviewed, focusing on their possible applications in different research
      fields. Clinical results of CD34+ selection and the possible future applications
      of this technology in the clinic are also reported.

PMID- 8562974
TI  - Cytokines in the acquired immunodeficiency syndrome and other infectious
      diseases.
AB  - The pathogenesis of several infectious diseases is frequently related not only to
      their etiological agents of viral, bacterial, or parasitic nature, but also to
      the host immune response. Both inflammatory responses and specific immune
      responses to the invading microorganisms are controlled by complex networks of
      intercellular signalling molecules, namely cytokines. This rapidly growing family
      of mediators includes lymphokines, interleukins, and molecules such as tumor
      necrosis factors and interferons. Patterns of cytokine production from antigen-
      or allergen-specific T lymphocytic cell clones have been identified, firstly in
      animal models and subsequently in man, and are commonly referred to as TH0, TH1,
      and TH2 profiles. The predominance of one of these profiles strongly influences
      the type of immune response (humoral versus cellular) and, at least in some
      experimental models, whether the immune response is protective or harmful. This
      is most convincingly demonstrated in models of parasitic diseases, but has also
      been hypothesized to be involved in the pathogenesis of human immunodeficiency
      virus infection and the acquired immunodeficiency syndrome. Earlier studies on
      human immunodeficiency virus infection revealed that the replicative capacity of
      this retrovirus, like the herpes viruses, is strongly influenced by the cytokine
      milieu of infected cells. Transcriptional and post-transcriptional regulation of
      human immunodeficiency virus expression by human cytokines are examples of the
      complex interdigitation of viruses with the host immune system.

PMID- 8562976
TI  - Simultaneous detection of delta F508, G542X, N1303K, G551D, and 1717-1G-->A
      cystic fibrosis alleles by a multiplex DNA enzyme immunoassay.
AB  - We describe the use of a polymerase chain reaction in conjunction with a DNA
      enzyme immunoassay for the simultaneous detection of five common cystic fibrosis
      mutations. The method is specific, sensitive, rapid, and proved effective in
      Guthrie card-based screening of cystic fibrosis mutations.

PMID- 8562975
TI  - Megestrol acetate in neoplastic anorexia/cachexia: clinical evaluation and
      comparison with cytokine levels in patients with head and neck carcinoma treated
      with neoadjuvant chemotherapy.
AB  - The aim of our study (clinical phase II open pilot study) was to evaluate the
      toxicity of megestrol acetate and its ability to increase appetite and body
      weight in patients with advanced-stage (III-IV) primary head and neck squamous
      cell carcinoma treated with neoadjuvant (primary) chemotherapy. Serum levels of
      interleukin-1 alpha and beta, interleukin-2 and 6, tumor necrosis factor-alpha,
      and the soluble receptor for interleukin-2 were evaluated before and after
      megestrol acetate treatment. The same cytokines and soluble interleukin-2
      receptor were also measured in culture medium of peripheral blood lymphocytes
      from the same patients after stimulation with phytohemagglutinin. From April 1993
      to February 1994, 11 male patients were enrolled in our study: their mean age was
      57.8 years (range 43-69 years). Megestrol acetate was administered at a dose of
      320 mg/day in the interval between chemotherapeutic cycles for a total of three
      consecutive cycles; 9 of the 11 patients could be evaluated (81.8%). Except for
      the performance status according to Karnofsky, all parameters were increased
      after megestrol acetate treatment. The average weight increased by 6.3 kg
      (13.2%), appetite by a score of 2.4 (38.6%) and the Spitzer's quality of life
      index by a score of 2.4 (36.2%). The performance status according to Karnofsky
      decreased in only 1 patient, remained the same in most patients, and in 2
      patients was slightly improved. No significant side effects were observed during
      treatment. Serum levels of interleukin-1 alpha and beta, interleukin-2 and 6,
      tumor necrosis factor-alpha, and soluble interleukin-2 receptor were
      significantly higher than in normal subjects, prior to treatment with megestrol
      acetate. These levels dropped after megestrol acetate treatment with a
      statistically significant decrease for interleukin-1 alpha and beta and tumor
      necrosis factor-alpha. There were no significant differences in the production of
      cytokines by peripheral blood lymphocytes stimulated with phytohemagglutinin from
      patients before megestrol acetate treatment and normal subjects, with the
      exception of interleukin-6 (higher in patients) and of soluble interleukin-2
      receptor (lower in patients). There was no significant difference in the
      cytokines and soluble interleukin-2 receptor produced in culture before and after
      megestrol acetate treatment, except for interleukin-6 which decreased after
      treatment.

PMID- 8562977
TI  - Asparaginase decreases clotting factors in vitro: a possible pitfall?
AB  - L-Asparaginase treatment of leukemia patients causes hemostatic problems. To
      investigate whether L-asparaginase influences coagulation studies, 63 blood
      samples of 21 healthy male donors were incubated with L-asparaginase for 30 min
      at room temperature. After treatment with 100 IU/ml L-asparaginase plasma
      fibrinogen (P = 0.002), plasma antithrombin (P = 0.0002), plasma protein C (P =
      0.0004), and plasma plasminogen (P = 0.0039) were decreased compared with
      controls. In contrast, a significant increase in plasma von Willebrand factor
      antigen (P = 0.08) and plasma thromboglobulin (P = 0.005) was observed. The
      decrease in plasma anti-thrombin (P = 0.001), plasma protein C (P = 0.0003), and
      plasma plasminogen (P = 0.0043) was also measurable after 0.05 IU/ml asparaginase
      treatment. The incubation with L-asparaginase was similar to the normal time from
      blood sampling to testing and hence the results suggest that L-asparaginase may
      directly attack proteins of the coagulation system during the interval between
      sampling and assay.

PMID- 8562979
TI  - Peripheral blood CD3 and CD4 T-lymphocyte reduction correlates with severity of
      liver cirrhosis.
AB  - Immunological disturbances with impairment of immune function and a higher
      incidence of lymphoproliferative disorders and other malignancies have been
      described in liver cirrhosis patients. To investigate the pathogenetic
      mechanism(s) involved in such associated we looked for a possible imbalance in
      peripheral blood T-lymphocyte subpopulations in patients with liver cirrhosis of
      differing severity. Immunophenotyping and counts of peripheral blood T-lymphocyte
      subpopulations were carried out using monoclonal antibodies conjugated with
      different fluorochromes in 31 consecutive cirrhotic patients and 23 matched
      healthy volunteers. Univariate and multivariate analyses of lymphocyte phenotype
      counts were performed and odds ratios were computed. Statistically significant
      associations, according to both univariate and multivariate analyses, were found
      between case/control status and mean CD3 and CD4 T-lymphocyte counts (P <
      0.0001). A strong correlation was found between the Pugh's index and CD3 and CD4
      lymphocyte counts, with a clear reduction of these phenotypes with increasing
      liver cirrhosis. Median CD3 and CD4 values were 2,283 and 1,329/microliters
      respectively among controls and 896, 801, and 492/microliters and 515, 514, and
      307/microliters, respectively in categories A, B, and C of Pugh's classification.
      Very high odds ratios were found using the median values of CD3 and CD4 as a
      threshold. There was a statistically significant decrease for each of the T-cell
      phenotypes studied (CD2, CD3, CD4, CD8, CD16, CD19, CD20, CD56, CD57) between
      patients and controls (P < 0.0001). The progressive and severity-related decrease
      in mean peripheral blood CD3 and CD4 counts in liver cirrhosis suggests a
      progressive impairment of protective immune function and may be a factor
      facilitating malignancy in cirrhotic patients.

PMID- 8562978
TI  - Evaluation of the fibrinolytic system in full-term neonates.
AB  - Plasminogen activity and antigen, euglobulin fibrinolytic activity, tissue-type
      plasminogen activator activity and antigen urokinase-type plasminogen activator
      antigen, plasminogen activator inhibitor-1 activity and antigen, plasminogen
      activator inhibitor-2 antigen, tissue-type plasminogen activator/plasminogen
      activator inhibitor complexes, alpha 2-antiplasmin, histidine-rich glycoprotein,
      and fibrinogen/fibrin degradation products were measured in blood samples taken
      from the umbilical vein of 100 healthy full-term newborns. Results were compared
      with a control group of 30 healthy adults. The overall fibrinolytic activity
      assessed on fibrin plates was significantly increased (P < 0.002). We also
      observed high tissue-type plasminogen activator activity levels (P < 0.001),
      whereas urokinase-type plasminogen activator antigen levels were lower than in
      adults. There was a significant reduction in plasminogen activity and antigen (P
      < 0.0001), plasminogen activator inhibitor-1 activity (P < 0.05), alpha 2
      antiplasmin (P < 0.0001), and histidine-rich glycoprotein (P < 0.0001), whereas
      plasminogen activator inhibitor-2, tissue-type plasminogen activator/plasminogen
      activator inhibitor complexes and fibrinogen/fibrin degradation products did not
      differ between groups. We conclude that in the newborn there is increased
      fibrinolytic activity, mainly due to increased plasminogen activators and reduced
      fibrinolysis inhibition, without systemic fibrinolysis and fibrinogenolysis.

PMID- 8562980
TI  - Glycation of lipoproteins and accelerated atherosclerosis in non-insulin
      dependent diabetes mellitus.
AB  - We used a new and remarkably simple method to examine the extent of in vivo
      lipoprotein glycation in type II diabetic patients with atherosclerosis and
      diabetic patients with no complications. Serum glycated lipoprotein levels were
      determined by agarose gel film electrophoresis in 48 non-diabetic control
      subjects and 39 diabetic patients, of whom 26 had no complications and 13 had
      atherosclerotic heart disease. Fasting serum glucose, glycohemoglobin and serum
      fructosamine concentrations (indicators of glycemia) and total cholesterol,
      triglyceride, low-density lipoprotein-, very low-density lipoprotein- and high
      density lipoprotein-cholesterol concentrations and the low-density
      lipoprotein/high-density lipoprotein ratio (serum lipid profile) were also
      determined in the control and diabetic subjects. Glycated low-density lipoprotein
      and very low-density lipoprotein concentrations were significantly increased in
      diabetic patients compared with controls; but only glycated very low-density
      lipoprotein was significantly increased in atherosclerotic patients compared with
      diabetics without complications. The lipid profile parameters were not
      significantly increased in patients compared with controls. In diabetics,
      especially those with poorly controlled hyperglycemia and atherosclerosis,
      glycation of lipoprotein fractions might be more important than serum lipid and
      lipoprotein abnormalities. The significant correlation between atherosclerosis
      and glycated very low-density lipoprotein, suggests that very low-density
      lipoprotein glycation could be responsible for the development of atherosclerosis
      in diabetes.

PMID- 8562981
TI  - Plasma and urine malondialdehyde levels in non-insulin-dependent diabetic
      patients with and without microalbuminuria.
AB  - Malondialdehyde, a marker of lipid peroxidation, was measured as thiobarbituric
      acid-reactive substance in 78 non-insulin-dependent diabetic patients and 28
      healthy subjects. Patients were divided into groups and subgroups according to
      the presence of microalbuminuria and other complications. Plasma and urine
      malondialdehyde concentrations were significantly higher in patients with and
      without microalbuminuria than in controls. In contrast to urine malondialdehyde,
      plasma malondialdehyde levels were significantly higher in microalbuminuric
      diabetes than in the normolbuminuric diabetic group. There was no correlation
      between malondialdehyde concentration and glycemic control. This study confirmed
      the existence of lipid peroxidation disorders in diabetic patients.

PMID- 8562982
TI  - Serum immunoglobulin levels in heterozygous subjects with immunoglobulin heavy
      chain constant region gene deletions.
AB  - The immunoglobulin heavy chain constant region locus is a multigene family
      composed of nine genes and two pseudogenes, whose high homology is often
      responsible for meiotic mispairings leading to deleted and duplicated haplotypes.
      These rearrangements have a population frequency of about 1.5% and 4.5%
      respectively, with a significant difference between deletions and duplications (P
      < 0.001). Both positive selection of duplications or negative selection against
      deletions can account for this imbalance. Serum levels of IgG and IgA subclasses,
      of IgE, of isohemagglutinins and of IgG antibodies to tetanus toxoid and
      pneumococcal antigens were evaluated in 11 heterozygous carriers of constant
      region deletions. There was no gross abnormality in serum IgG and IgA subclass
      levels, with the possible exception of G1-deleted individuals; furthermore,
      isohemagglutinins and anti-tetanus toxoid and pneumococcal IgG antibodies are in
      the normal range, suggesting that the humoral immune response is normal in these
      carriers. The influence of single and multiple immunoglobulin heavy chain
      constant region gene deletions on the humoral response is discussed.

PMID- 8562983
TI  - Proving that less is more: linking resources to outcomes.
AB  - Advocates of inpatient managed care employing clinical pathways are confident
      that this patient management strategy reduces cost while promoting optimal
      patient outcomes. Other health care professionals are concerned that cost
      reductions place patients at higher risk for adverse health events. Research is
      needed to demonstrate the true impact of cost-containment strategies on clinical
      outcomes. The article describes a study in progress comparing patients
      conventionally managed by their physicians with similar patients whose overall
      management involved a nurse case manager. This study explores the issue of
      resource costs that can be linked to clinical and financial outcome measures.

PMID- 8562984
TI  - Improving the process of care: the cost-quality value of interdisciplinary
      collaboration.
AB  - A multidisciplinary group of clinicians and administrators were convened to find
      innovative ways to contain costs and improve the quality of care on an inpatient
      orthopedic unit. This group was charged with examining all phases of care and
      recommending changes. The team proved to be a model of effective, successful
      collaboration and has enabled ambitious goals to be realized on this unit. The
      article outlines changes related to preoperative, intraoperative, and
      postoperative care and discusses the dynamics of effective interdisciplinary
      professional collaboration.

PMID- 8562985
TI  - Activity-based management: a tool to complement and quantify continuous quality
      improvement efforts.
AB  - An activity-based cost management system provides a framework to integrate the
      disciplines of quality and cost management. The integration occurs through the
      development of performance measures that collectively measure operations with
      respect to internal and external customers. It is the measurement process that
      allows management staff to evaluate where they are, determine where they want to
      be, and set a course of action that closes the gap between the two.

PMID- 8562986
TI  - Managed care and total quality management: a necessary integration.
AB  - The process of quality improvement/total quality management (QI/TQM) plays a key
      role in the delivery of health care in a managed care system. The concepts and
      ideas surrounding QI/TQM and managed care are interrelated, and the success of
      health care delivery depends on the integration and coexistence of these two
      philosophies. In looking more closely at these concepts, it becomes clear that
      the principles of QI/TQM must underlie strategic decisions involved in the
      implementation of a managed care system. Nurses play a key role in the success of
      this integration as nurse case managers, nurse practitioners, and nurse
      administrators. They have a direct impact on the many variables and goals of both
      QI/TQM and managed care.

PMID- 8562987
TI  - The imperative of outcomes analysis: an integration of traditional and
      nontraditional outcomes measures.
AB  - The health care industry is compelled to reduce costs while providing high
      quality patient care. Outcomes analysis enables monitoring and maintenance of
      quality of care in our rapidly changing practice environment. Comprehensive
      outcomes research cannot occur, however, without a database incorporating
      practice-related data, interventions and components of care, and outcomes of
      care. The article reports the design and proposed implementation of an outcomes
      assessment infrastructure in a multifacility health maintenance organization in
      Northern California. The infrastructure integrates traditionally measured
      outcomes and cost data with nontraditional, nurse-influenced, health-related
      outcomes.

PMID- 8562988
TI  - Assessing the congruence of nursing models with organizational culture: a quality
      improvement perspective.
AB  - Model-based practice was identified by the Nursing Department at Riverview Health
      Centre, a 320-bed long-term care facility located in Winnipeg, Manitoba, as
      having the potential to enhance care quality significantly. To achieve real
      impact in the clinical setting, however, the model selected would need to reflect
      closely the culture and values of the department. It was decided to explore these
      phenomena using cross-method triangulation involving a cultural assessment survey
      (the Nursing Unit Cultural Assessment Tool) and focus groups. Patient comfort and
      empathy emerged consistently as core values for staff. Greater appreciation of
      the depth and complexity of the nursing department culture and values has
      provided invaluable direction vis-a-vis conceptual model selection.

PMID- 8562989
TI  - Consumer satisfaction with nursing care in a rural community hospital emergency
      department.
AB  - The article describes a study undertaken to assess patient satisfaction with
      nursing care in a rural hospital emergency department with respect to
      psychological safety, discharge teaching, information giving, and technical
      competence. This descriptive research utilized Davis' Consumer Emergency Care
      Satisfaction Scale to determine the degree to which 52 patients perceived overall
      satisfaction with nursing care. Findings indicated that patients were satisfied
      with nursing care. No statistically significant effect of gender or education
      level on consumer satisfaction or on any subscale was detected, but African
      American consumers were less satisfied with discharge teaching, which may suggest
      that discharge teaching should reflect the cultural diversity of consumers
      presenting to the emergency department. Nursing staff may need to spend more time
      with rural African American consumers. Staff may need to be inserviced to meet
      the cultural and educational needs of African Americans.

PMID- 8562990
TI  - Improving the outcome of emergency department patients with a chief complaint of
      chest pain.
AB  - Preliminary data developed by the Health Care Financing Administration under its
      pilot cooperative cardiovascular screening project indicate that 50 percent of
      Medicare heart attack patients arriving in emergency departments who are
      appropriate for thrombolytic therapy do not receive it within the time period
      specified by the American College of Cardiology. Indicators developed for quality
      assurance monitoring and evaluation of a hospital emergency department prompted
      closer review of some cases. It was determined that a critical outcomes team
      using the principles of total quality management and the FOCUS-PDCA models should
      be empowered to deal with these issues. Through this process, the need for the
      development of a chest pain center at the hospital was identified and supported.

PMID- 8562991
TI  - Conflicts experienced by quality assurance/improvement professionals: A Delphi
      study.
AB  - A Delphi survey was conducted to investigate the frequency and importance of
      conflicts identified by quality assurance/improvement professionals as well as
      the actions taken and resources used to deal with the conflicts. Responses to
      three rounds of the Delphi survey from 86 participants indicated that the
      predominant conflicts involved intrapersonal concerns, such as worry about the
      future, interpersonal and political barriers to change in quality work, and,
      rarely, ethical conflicts. A variety of collaborative and educational strategies
      were used to deal with conflicts. Results may be useful to examine from the
      perspective of health care professionals currently involved in quality work.

PMID- 8562992
TI  - Tissue staining for Helicobacter pylori in intestinal metaplasia: correlation
      with its extension and histochemical subtypes.
AB  - The role played by Helicobacter pylori (Hp) infection in the occurrence of non
      cardial gastric adenocarcinoma is suggestive but still debated. This study aimed
      to evaluate: a) the prevalence of Helicobacter-like organisms in antral bioptic
      specimens of 291 patients with chronic gastritis with antral atrophy and
      different subtypes of intestinal metaplasia (IM); b) the presence of a possible
      different positive tissue staining for the bacteria in the complete and
      incomplete intestinal metaplasia. Of the 291 patients, 222 cases (76.3%) showed
      type I IM, 28 cases (9.6%) type II IM and 41 cases (14.1%) type III IM.
      Helicobacter-like organisms were found in 42.9% of cases and positive tissue
      staining rate appeared to be inversely related to the extension of IM (58.7% in
      IM extended in less than 30% of specimens, 30.2% in IM extended between 30% and
      60%, 2.7% in IM exceeding 60% of the biopsed area). The inverse correlation
      between lower positive tissue staining for Helicobacter-like organisms and
      greater extension of IM was statistically significant (p < 0.001). Incomplete
      metaplasia appeared to be unrelated to age and associated with a lower positive
      tissue staining for Helicobacter-like organisms; among patients with type I
      metaplasia, 118/222 showed Hp-positive bioptic specimens, vs 7/69 of types II and
      III (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562993
TI  - Thyroid involvement in patients with active inflammatory bowel diseases.
AB  - Previous studies have documented an association between systemic diseases and
      disorders of the thyroid gland, expressed by an enlargement of the thyroid and by
      the presence of anti-thyroid antibodies. Chronic inflammatory bowel diseases
      (IBD, ulcerative colitis and Crohn's disease) may also present a multi-organ
      involvement, including the biliary tree, joints and uvea. To detect a possible
      subclinical thyroid involvement, thyroid volume and function were assessed in 31
      patients with IBD in active phase and in 50 control subjects. Thyroid volume was
      calculated by ultrasonography on the basis of the three maximum diameters of the
      2 lobes. A blood sample was taken to determine free thyroid hormones, TSH, and
      anti-thyroid antibodies. In patients with IBD, thyroid volume was increased on
      average by 35%, and the prevalence of thyroid enlargements (antero-posterior
      diameter > 20 mm) was 3 times higher (45% vs 16%). Free thyroxine was increased
      by nearly 50%, but only 10% of patients had anti-thyroid antibodies. Alterations
      of thyroid volume and function are present in IBD, even in the absence of
      clinically-detectable thyroid disease. The association of IBD with thyroid
      disorders, as well as the involvement of various organs, confirms the view that
      IBD is a systemic disease.

PMID- 8562994
TI  - Serum CA 242 in pancreatic cancer. Comparison with CA 19-9 and CEA.
AB  - Serum CA 242, CA 19-9 and CEA concentrations were determined in 94 subjects
      divided into 5 groups: Group 1 consisted of 22 healthy subjects; Group 2
      consisted of 40 patients with pancreatic adenocarcinoma; according to Cubilla and
      Fitzgerald's classification, 11 tumours were Stage I, 4 were Stage II, and 25
      were Stage III. Group 3 consisted of 10 chronic pancreatitis patients, group 4 of
      10 acute pancreatitis patients, group 5 of 12 patients with nonpancreatic
      digestive carcinomas. Ten of these 12 patients had distant metastases. The
      sensitivity of CA 19-9 in the diagnosis of pancreatic cancer was higher than that
      of CEA and CA 242 (p < 0.05 and p < 0.005, respectively). In Stage I cancer
      patients the sensitivity of the markers studied was less than 50% (45% for CA 19
      9, 18% for CEA, and 9% for CA 242) whereas most of the 25 patients with
      metastatic tumours of the pancreas had elevated serum levels of all 3 markers.
      The various combinations of the three markers did not significantly improve the
      sensitivity in diagnosing pancreatic cancer. No relationship was found between
      the localization of the tumour and the serum levels of the 3 markers studied.
      Similarly, no differences were found between patients with cholestasis and those
      without. The specificity of the 3 markers, evaluated in patients with benign
      pancreatic diseases, was 100% for CA 242, 90% for CA 199 and 70% for
      CEA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8562995
TI  - HCV third generation test in hemodialysis patients.
AB  - In order to evaluate the sensitivity of HCV test, Ortho Second and Third
      Generation HCV Elisa Tests were used in 315 sera collected from dialysis
      patients. The agreement between the two tests was 96.5%. RIBA Second and Third
      generation and PCR were tested in the eleven discordant sera and in specimens
      collected in 1992 from the same patients and in 20 Ortho-2 and Ortho-3 HCV
      negative patients. Ortho-3 test is capable of detecting anti-HCV seroconversion
      earlier than Ortho-2 with increased sensitivity and specificity, as is confirmed
      by RIBA and PCR tests.

PMID- 8562996
TI  - Adenocarcinoma and atypical carcinoid: morphological study of a gastric collision
      type tumour in the carcinoma-carcinoid spectrum.
AB  - We report the morphological features of an unusual cardial gastric tumour in a 72
      year-old white man. Histologic examination revealed two adjacent, "side by side",
      but not merged, components: a poorly differentiated one and a typical moderately
      differentiated gastric adenocarcinoma. Both components were also found in the
      metastatic lymph nodes. Histochemical (Grimelius) and immunohistochemical (neuron
      specific enolase, chromogranin A, synaptophysin) studies revealed the endocrine
      nature of the poorly differentiated component, which however, was not argentaffin
      and did not show immunoreactivity for specific endocrine substances. The
      neoplastic lesion was classified in the carcinoma-carcinoid spectrum as collision
      type tumour. Our data suggest the double and independent origin of the two
      components.

PMID- 8562997
TI  - Emergency transjugular intrahepatic portosystemic shunt in patients with active
      variceal bleeding and hepatocarcinoma.
AB  - Variceal hemorrhage is a leading cause of death in patients with hepatic
      cirrhosis. We report the case of two cirrhotic patients with hepatocarcinoma in
      whom oesophageal varices bled repeatedly. Because the bleeding was not controlled
      by sclerotherapy, vasopressin or Blakemore balloon, the patients were evaluated
      for emergency transjugular intrahepatic portosystemic shunt. After the procedure,
      portal vein pressure decreased from 45.5 mmHg to 18 mmHg and from 44 mmHg to 19
      mmHg respectively and no filling of varices was evident at venogram or endoscopy.
      After 16 and 8 months respectively, bleeding had not recurred, and no episodes of
      encephalopathy were referred. Transjugular intrahepatic portosystemic shunt
      should always be considered an effective emergency therapeutic alternative to
      shunt surgery in patients with active variceal bleeding when traditional
      management fails.

PMID- 8562998
TI  - Pathogenetic mechanisms of inflammatory bowel disease.

PMID- 8562999
TI  - Bile acids: physico-chemical properties, function and activity.

PMID- 8563000
TI  - Therapeutic index of taurocholate or tauroursodeoxycholate in experimental drug
      induced cholestasis.
AB  - The therapeutic index of either taurocholate (TC) or tauroursodeoxycholate (TUDC)
      administration in the treatment of drug-induced cholestasis was evaluated in
      perfused rat liver using a dose-response study. During estradiol-17-beta
      glucuronide cholestasis, TC was more effective than TUDC in ameliorating bile
      flow but showed a low margin of safety since high doses caused additional
      toxicity. In contrast, TUDC ameliorated cholestasis even at very high doses with
      no adverse effects. In the model of chlorpromazine cholestasis, TC infusion did
      not correct but rather aggravated cholestasis, whereas TUDC at nonsaturating
      doses reversed the cholestasis and only at very high doses caused some toxicity.
      TUDC shows a good therapeutic index and may be employed with a reasonable margin
      of safety in the treatment of drug cholestasis.

PMID- 8563001
TI  - Acute ethanol hepatotoxicity is modulated by bile salt hydrophilic-hydrophobic
      properties.
AB  - The influence of the hydrophobic-hydrophilic properties of bile salts (BS) on
      acute ethanol hepatotoxicity was investigated. Bile flow, biliary BS secretion
      and enzyme (LDH,AST) release in the perfusate were measured before and after
      exposure to low (0.1%) or high (1%) doses of ethanol in in vitro isolated livers
      perfused with 1 microM/min taurocholate (TCA), tauroursodeoxycholate (TUDCA) or
      taurodeoxycholate (TDCA). Ethanol promotes a rapid decrease of basal bile flow
      and BS secretion in TCA-perfused livers [-28% of basal values with 0.1% (N = 6),
      and -35% with 1% ethanol (N = 6)]. Bile flow and BS secretion were minimally
      decreased by ethanol in livers perfused with a hydrophilic BS (TUDCA) [-8%
      decrease of basal values with 0.1% ethanol (N = 6), and -10% with 1% ethanol (N =
      9); p < 0.02 vs TCA-perfused livers]. In contrast, when livers were perfused with
      a hydrophobic BS (TDCA), ethanol showed a higher cholestatic effect than either
      TCA- or TUDCA-perfused livers. Enzyme release in the perfusate was not modified
      by 0.1% ethanol, while 1% ethanol promoted a 4-5 fold increase in LDH and AST
      release in the perfusate of TCA-perfused livers with respect to a mere 2-fold
      increase in TUDCA-perfused livers and a 6-7 fold increase in TDCA perfused livers
      (p < 0.03). In conclusion, we showed that TUDCA almost completely counteracts the
      cholestatic and cytolitic effects promoted by ethanol in the isolated perfused
      rat liver.

PMID- 8563002
TI  - Familial environment and HCV infection.

PMID- 8563003
TI  - First bleeding episode from oesophageal varices in cirrhotic patients: a
      prospective study of endoscopic predictive factors.
AB  - Two hundred patients affected by liver cirrhosis and oesophageal varices were
      studied in 9 Gastrointestinal Units in Lombardy (Northern Italy) in order to
      assess factors possibly related to variceal bleeding. Only patients without any
      previous episode of gastrointestinal bleeding were included in the prospective
      evaluation. For each patient demographic data, aetiology of cirrhosis, various
      clinical and biochemical parameters able to group patients into the three Child
      Pugh Classes, endoscopic items for calculation of Beppu's and of NIEC prognostic
      scores were recorded on computerized cards. Patients were regularly interviewed
      every three months for one year and underwent an upper gastrointestinal endoscopy
      at enrollment, after six months and in case of bleeding. Within the twelve-month
      follow-up period, 29 out of the 200 patients (14%) bled and 52 out of 200 died
      (26%). In 16 of the 52 patients who died (59% of bleeding patients) death was
      directly related to gastrointestinal bleeding. Bleeding from oesophageal varices
      was endoscopically proven in 19/29 patients, in another 9 bleeding was classified
      as from unknown source and in one patient a bleeding gastric ulcer was diagnosed.
      Univariate analysis of all the recorded clinical, biochemical and endoscopic
      parameters, performed by Chi-square method and Fisher exact test showed that the
      presence of RWM (p < 0.001) was the only factor significantly associated to
      variceal bleeding within one year. Relationship between size of varices and
      bleeding was very close to the statistical significance but did not achieve it (p
      = 0.058).

PMID- 8563004
TI  - Peripheral neuropathy in liver cirrhosis. A clinical and electrophysiological
      study.
AB  - Clinical symptoms and/or signs of peripheral neuropathy were found in 17 of the
      19 patients we studied with liver cirrhosis. In 16 of the 19 patients
      electrophysiological abnormalities were also observed. Mild-moderate alterations
      involved both motor and sensory fibres, with a higher incidence in the lower
      rather than upper limbs, and indicated a fibre loss rather than a fibre
      demyelination. These changes were observed in both alcoholic and non-alcoholic
      cirrhotics, suggesting a primary role of liver cirrhosis per se. In fact, both
      the clinical and electrophysiological abnormalities were related to the severity
      of the liver disease. A careful clinical examination could reveal the presence
      and extent of neuropathy in most cirrhotic patients.

PMID- 8563005
TI  - IgG anti-betalactoglobulin (betalactotest): its usefulness in the diagnosis of
      cow's milk allergy.
AB  - The aim of this prospective study was to evaluate the distribution of serum
      values of IgG anti-betalactoglobulin in 3 groups of subjects: a) 218 healthy
      subjects (138 M, 80 F) with age ranging from 1 month to 6 years; b) 205 patients
      with cow's milk protein allergy (CMPA) (130 M, 75 F) aged between 1 month and 4
      years; c) 96 patients (50 M, 46 F) with symptoms compatible with CMPA, but
      suffering from other diseases (age range 1 month-6 years). The IgG anti
      betalactoglobulin values were obtained using a new commercially available
      immunoenzymatic method. There was a marked difference in the distribution of IgG
      antibetalactoglobulin values in the 3 study groups. In healthy controls the value
      corresponding to the 5th centile was 5%, to the 50th centile 17%, to the 90th
      centile 48%. In the gastroenterological controls, 5th centile was 5%, 50th
      centile 15% and 90th centile was 56%. In the patients with CMPA, 5th centile was
      27%, 50th centile 101% and 90th was 147%. The distribution of the values was
      therefore significantly different in the CMPA group from that of the other 2
      groups (p < 0.0001). Plotting receiver operating characteristics curves, we have
      indicated a betalactotest value of 36% as a cut-off with the highest diagnostic
      accuracy (89% sensitivity, 85% specificity). We suggest that the betalactotest
      should be used to confirm diagnosis in patients with suspected CMPA; with a cut
      off of over 48% we found only one false positive for diagnosis of CMPA in
      patients presenting other diseases with an identical clinical picture.

PMID- 8563006
TI  - Efficacy of pneumatic dilatation for pyloric stenosis: an 18-month survey.
AB  - The efficacy of pneumatic dilatation with Rigiflex balloons as a treatment for
      pyloric peptic stenosis was tested in 18 patients. The patients underwent
      endoscopic dilatation in one sitting, the size of the balloons being gradually
      increased for a total of 3 minutes. Patients were also treated with omeprazole in
      the follow-up period. Pneumatic dilatation of upper digestive tract strictures
      has proved to be an effective and safe technique, showing remarkable advantages
      over the traditional surgical treatment. It could represent the first step in a
      therapeutic approach.

PMID- 8563007
TI  - Non-alcoholic steatohepatitis. Report of five cases and review of the literature.
AB  - We describe three men and two women, aged 18-50, with an occasional finding of
      increased aspartate and alanine aminotransferase and gamma-glutamyl
      transpeptidase levels in the absence of any drug treatment and past or current
      alcohol abuse. Two patients were overweight (body mass index 29 and 32,
      respectively) and physical examination was normal in all but one case. Tests for
      hepatitis A, B and C, Epstein-Barr virus, cytomegalovirus, toxoplasma and
      autoimmune hepatitis were negative and metabolic diseases (Wilson's disease,
      haemochromatosis, alpha-l-antitrypsin deficiency) were excluded by specific
      tests. Ultrasound liver scan revealed massive steatosis in all patients. Liver
      histology showed diffuse steatosis and parenchymal inflammation in all cases,
      with concomitant fibrosis and Mallory bodies in three of them. Findings were
      consistent with non-alcoholic steatohepatitis, a rare condition with potential
      progression to cirrhosis in a minority of cases. This disease, for which no
      treatment is currently available, must be considered in all subjects with
      elevated aminotransferases, in the absence of known causes of liver damage.

PMID- 8563008
TI  - The protective effect of hydrophilic bile acids on bile acid hepatotoxicity in
      the rat.
AB  - Taurochenodeoxycholate (TCDC) (or taurocholate, TC) excessively i.v. infused in
      rats causes an acute cholestasis accompanied by an excessive excretion of various
      proteins (lactate dehydrogenase, LDH, albumin, etc.) into the bile. This
      cholestasis was initially found to be effectively prevented by a simultaneous
      infusion of tauroursodeoxycholate (TUDC). Later this property was found to be
      shared by glycoursodeoxycholate (GUDC) and tauro (and glyco) alpha and beta
      muricholate (MC) all known to be relatively hydrophilic. The extent of the
      preventative effect appears to be comparable for taurine and glycine conjugates
      of all three bile salts (UDC, alpha-MC and beta-MC). An albumin leakage into the
      bile enhanced by TCDC infusion appears to be mainly from albumin in the serum,
      since i.v. injected 125I-human serum albumin excretion into the bile paralled the
      rat albumin excretion. Despite very drastic biochemical abnormalities induced by
      TCDC infusion, morphological correlates in the liver are scarce both from light
      and electron microscopic examinations, the only correlate with biochemical
      parameters being a sporadic necrosis of hepatocytes, especially in the periportal
      areas. Although there is not sufficient morphological evidence, it appears that
      TCDC infusion causes a direct communication between serum and bile leading to a
      rapid leakage of large molecules such as albumin and even gamma-globulin.
      Conjugates of hydrophilic bile salts such as UDC, alpha-MC and beta-MC
      efficiently prevent such bile abnormalities but their hydrophilicity is not the
      sole determinant of this property since a more hydrophilic bile salt such as
      taurodehydrocholate does not possess this property. The underlying mechanism(s)
      for this protective property remains uncertain.

PMID- 8563009
TI  - Bile salt-membrane interactions and the physico-chemical mechanisms of bile salt
      toxicity.
AB  - We present evidence that ursodeoxycholate prevents toxicity of more hydrophobic
      bile salts by inhibiting micellar solubilization of membrane lipids. Using both
      centrifugal ultrafiltration and gel filtration methods we studied leakage of
      inulin from vesicles composed of egg phosphatidylcholine and cholesterol. We
      observed that the addition of tauroursodeoxycholate to taurodeoxycholate reduced
      leakage of inulin from large unilamelar vesicles compared to that seen with
      taurodeoxycholate alone. This protective effect was observed only at high
      membrane cholesterol:phospholipid ratios (> or = 0.5). By gel filtration we found
      that fractional leakage of inulin from vesicles was identical to fractional
      phospholipid solubilization, indicating that release of inulin from vesicles
      results from membrane dissolution rather than from increased permeability of
      otherwise intact membranes. Addition of tauroursodeoxycholate to
      taurodeoxycholate was found to suppress the dissolution of phospholipid from
      cholesterol-rich vesicles. Bile salts were found to absorb to vesicles with an
      affinity proportional to their relative hydrophobicity, as estimated by reverse
      phase HPLC. Adsorption affinity decreased progressively with increasing membrane
      cholesterol content. Different bile salts displaced each other from membranes in
      proportion to their respective binding, affinities. Tauroursodeoxycholate, which
      absorbed to membranes with low affinity, displaced taurodeoxycholate from
      vesicles only weakly. Based on these findings we postulate that bile salts may
      damage the liver through solubilization of canalicular membrane lipids.
      Ursodeoxycholate may protect the liver by inhibiting dissolution of the
      cholesterol-rich canalicular membrane by more hydrophobic endogenous bile salts.
      Biliary secretion of vesicles rich in phosphatidylcholine may buffer the
      intermicellar concentration of bile acids at levels below those required to
      disrupt the cholesterol-rich canalicular membrane; thus biliary vesicle secretion
      may have evolved as a mechanism to protect the biliary epithelium from injury by
      luminal bile salts.

PMID- 8563010
TI  - TUDCA and UDCA are incorporated into hepatocyte membranes: different sites, but
      similar effects.
AB  - The aim of this paper is to point out that: 1) CDCA and DCA increase the polarity
      of cell membranes and cause the release of cholesterol and phospholipid from the
      membranes; 2) the extent of this damage is inversely correlated with the
      cholesterol content of the membrane investigated; 3) UDCA, TUDCA and GUDCA
      decrease membrane polarity; 4) they prevent membrane damage when added prior to
      CDCA or DCA; 5) UDCA appears to be incorporated into the apolar domain of the
      membrane, TUDCA, GUDCA into the interface; 6) UDCA decreases HLA class I
      expression on hepatocyte membranes; 7) CDCA induces GLDH-release from liver
      mitochondria and increases mitochondrial membrane polarity and mobility; and 8)
      UDCA reduces the release of GLDH from mitochondria caused by CDCA.

PMID- 8563011
TI  - Aspects of the sequencing of carbohydrates and oligonucleotides by matrix
      assisted laser desorption/ionization post-source decay.
AB  - The possibility of structural elucidation of carbohydrates and oligonucleotides
      by matrix-assisted laser desorption/ionization followed by post-source decay
      (MALDI-PSD) is investigated. Spectra of both classes of compounds exhibit the
      better signal-to-noise ratios for the intact species in the negative-ion mode,
      but the most informative spectra for structural elucidation by PSD are obtained
      in the positive-ion mode. A novel fragmentation mode is demonstrated on a model
      sialylated complex type N-linked oligosaccharide. Prompt fragmentation in the
      positive-ion mode can remove the sialic acids at high laser irradiance if a
      suitable matrix is used. The remaining sugar backbone is then characterized by
      post-source decay. A modified oligonucleotide is analyzed with 3-hydroxypicolinic
      acid as the matrix and ammonium tartrate to displace sodium. Enough structural
      information is obtained to verify the modification.

PMID- 8563012
TI  - Mass spectrometry of lens crystallins: bovine beta-crystallins.
AB  - The bovine beta-crystallins have been isolated by gel permeation chromatography
      (GPC) and fast protein liquid chromatography (FPLC). Electrospray ionization mass
      spectrometric examination of the resulting fractions confirms the relative
      molecular masses of three bovine beta-crystallins, i.e. beta B1, beta B2 and beta
      A2, only one of which (beta B2) has been reported previously by mass
      spectrometry. The sequence of beta B3 is shown to be incorrect as the identity of
      this protein was confirmed by FPLC, sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and matrix-assisted laser desorption ionization
      (MALDI) mass analysis of a tryptic digest of this protein. ESI analysis of the
      remaining beta subunits, i.e. beta A1, beta A3 and beta A4, suggests the
      published sequences of these proteins also contain errors. The major components
      observed in the beta H (i.e. octameric) and beta L (trimeric) aggregates of the
      beta-crystallins are shown to be consistent with subunit compositions determined
      by SDS-PAGE. A number of cleavage products of beta-crystallins were also
      identified, i.e. species with masses corresponding to beta B1(2)-203, beta B1(2)
      197, beta B8(2)-204, beta B1(2)-196 were detected in the ESI mass spectra
      following isolation of the beta B2 fraction from one-year-old lenses by FPLC. A
      species with mass of beta B6(1)-244 is also observed in the ESI mass spectrum of
      the beta H fraction isolated by GPC. The largest and most hydrophobic of the beta
      crystallins, beta B1, is detected in the beta H aggregate but not following FPLC
      purification of a fraction containing beta B1 and beta B2. A variety of different
      methods (including MALDI) were used to examine this fraction but none enabled the
      successful analysis of beta B1 in the deaggregated protein. Finally, this work
      demonstrates the advantages and some of the difficulties in mass spectrometric
      characterization of this class of proteins.

PMID- 8563013
TI  - Isolation and characterization of conopeptides by high-performance liquid
      chromatography combined with mass spectrometry and tandem mass spectrometry.

PMID- 8563014
TI  - Electrospray tandem mass spectrometry of nucleotides.
AB  - The tandem mass spectra (MS/MS) following electrospray ionization of nucleotides
      (from 2- to 6-mers) have been examined under a range of collision and ionization
      conditions. In general, abundant peaks due to the free bases and phosphate groups
      are observed, along with a limited number of sequence ions. A number of
      strategies for increasing the extent of the observed fragmentation were
      investigated. Increasing the skimmer potential of the ion source, thereby
      increasing the initial internal energy of the incident ions, did not
      significantly enhance the sequence-specific fragmentation, although the relative
      intensities of fragment ions increased. In MS/MS spectra of different adducts
      (i.e. [M + H]+, [M-H]-) of dinucleotides the intensity of the ions due to the
      bases (BH2+ or B-) is dependent on both the base position (i.e. either 3' or 5')
      and the nature of the adduct ion. These data show that MS/MS spectra of [M-H]-
      ions of dinucleotides generated by electrospray ionization may be equally as
      diagnostic as MS/MS spectra obtained following fast-atom bombardment. With [M +
      Li]+ ions, more sequence ions were observed compared to the corresponding
      protonated and deprotonated species. For oligonucleotide hexamers, MS/MS spectra
      of the [M-2H]2- ions show fragment ions due to loss of bases followed by cleavage
      of the 3' C--O bond in the sugar from which the base is lost (i.e. w ions);
      however, a strong preference for loss of any particular base is not observed.
      Finally, MS/MS spectra of 5'-ApCpC-3' and 5'-d(AGGCCT)-3' obtained on a magnetic
      sector orthogonal acceleration time-of-flight mass spectrometer demonstrate the
      potential utility of this instrumental configuration for MS/MS analysis of
      oligonucleotides.

PMID- 8563015
TI  - Analysis of double-stranded polymerase chain reaction products from the Bacillus
      cereus group by electrospray ionization Fourier transform ion cyclotron resonance
      mass spectrometry.
AB  - The analysis of polymerase chain reaction (PCR) products by electrospray
      ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI
      FTICR) has been achieved. Specifically, a 105 base-pair nucleotide portion of the
      ribosomal spacer region was amplified in two members of the B. cereus group (i.e.
      B. thuringiensis and B. cereus) using PCR. These amplified regions were then
      analyzed by gel electrophoresis and ESI-FTICR. Based on the predicted sequence of
      the PCR products for each organism, the mass measurement using ESI-FTICR matched
      the theoretical mass within experimental error and was consistent with gel
      electrophoresis results. In contrast, for the typical several hour time-scale of
      the gel electrophoresis experiment, the mass spectrometric analysis was completed
      in a matter of minutes. To our knowledge, this constitutes the first report
      demonstrating the ionization and detection of a double-stranded PCR product by
      ESI-MS. This preliminary result indicates the potential use of ESI-MS to analyze
      PCR products on a rapid time-scale, with potential for medical and taxonomic
      applications.

PMID- 8563016
TI  - Negative ionization micro electrospray mass spectrometry of oligonucleotides and
      their complexes.
AB  - The utility of negative ionization micro electrospray (microspray) mass
      spectrometry is demonstrated for detection of oligonucleotides and their non
      covalent complexes. A simple microspray ionization source is fabricated from an
      outer stainless-steel needle and an inner fused-silica capillary. Under these
      conditions, the liquid flow rate can be reduced 15-fold from 7.5 microL/min to
      0.5 microL/min. Studies of a 14-mer DNA oligonucleotide show no change in the
      charge-state distribution and quantity of adducted salt ions during the
      microspray process compared to pneumatically assisted electrospray mass
      spectrometry. The microspray ion source is less sensitive to the presence of
      solution buffers, and an 11-fold increase in integrated ion abundance from
      oligonucleotide analyte is observed with a 10 mM concentration of ammonium
      acetate, compared to pneumatically assisted nebulization (PAN). A > 100-fold
      increase in the duplex:single strand ratio for a 14-mer oligodeoxynucleotide and
      its complementary strand is observed using the microspray ion source relative to
      experiments performed with PAN. Studies of duplexes between DNA and a peptide
      nucleic acid suggest that this effect may be related to the degree of adduction
      of counterions to the DNA during ionization.

PMID- 8563017
TI  - Coaxial continuous-flow fast-atom bombardment vs electrospray ionization: a
      sensitivity comparison on a magnetic sector instrument.
AB  - The performance of an electrospray (ESI) source was evaluated and compared to
      that of a coaxial continuous-flow fast-atom bombardment source on a magnetic mass
      spectrometer using ten different peptides over the mass range of 400 to 3500 Da
      and using a variety of scanning modes. Results show that sensitivities using the
      two ionization techniques are similar, with limits-of-detection in the attomole
      to low femtomole range. In addition, proteins can be routinely detected using ESI
      at femtomole levels. The observance of the noncovalent complex of RNase A and
      cytidine 2'-monophosphate yields evidence that these complexes can be studied
      using instruments that operate at high accelerating voltages.

PMID- 8563018
TI  - Advanced stored waveform inverse Fourier transform technique for a matrix
      assisted laser desorption/ionization quadrupole ion trap mass spectrometer.
AB  - The stored waveform inverse Fourier transform (SWIFT) technique is used for
      broadband excitation of ions in an ion-trap mass spectrometer to perform mass
      selective accumulation, isolation, and fragmentation of peptide ions formed by
      matrix-assisted laser desorption/ionization. Unit mass resolution is achieved for
      isolation of ions in the range of m/z up to 1300 using a two-step isolation
      technique with stretched-in-time narrow band SWIFT pulses at the second stage.
      The effect of 'stretched-in-time' waveforms is similar to that observed
      previously for mass-scan-rate reduction. The asymmetry phenomenon resulting from
      the stretched ion-trap electrode geometry is observed during application of
      normal and time-reversed waveforms and is similar to the asymmetry effects
      observed for forward and reverse mass scans in the resonance ejection mode. Mass
      selective accumulation of ions from multiple laser shots was accomplished using a
      method described earlier that involves increasing the trapping voltage during ion
      introduction for more efficient trapping of ions.

PMID- 8563019
TI  - The application of mass spectrometry to the study of evolutionary trends in
      amphibians.
AB  - The glandular secretions of the skin of Litoria rubella specimens collected from
      five locations on the eastern seaboard of Queensland (Australia) contain the
      three tryptophyllin peptides Phe Pro Trp Leu (NH2), Phe Pro Trp Pro (NH2) and Phe
      Pro Phe Pro Trp Leu (NH2). The relative proportions of these peptides in the
      glandular secretion are associated with geographic location, i.e. Phe Pro Trp Pro
      (NH2) is a minor component of the peptide mixture in frogs from southern
      Queensland, but becomes significantly more abundant as the location becomes more
      northerly. This trend indicates an evolutionary change in the animal, but for
      what reason, and over what timescale is not known at this time.

PMID- 8563020
TI  - Retinoid signaling and the generation of regional and cellular diversity in the
      embryonic mouse spinal cord.
AB  - Retinoid-dependent gene expression accompanies the emergence of distinct regions
      and cell classes in the mouse spinal cord around midgestation. We asked whether
      changes in the expression of retinoid signaling molecules and retinoid-responsive
      genes reflect the establishment of this regional and cellular diversity. At
      E10.5, retinoic acid (RA) receptors (RAR)alpha, RAR beta, the retinoid X receptor
      (RXR) gamma, cellular RA binding protein (CRABP)I, CRAPBII, and cellular retinol
      binding protein (CRBP)I mRNAs are found throughout the entire anterior-posterior
      (AP) axis of the cord, as is RA (Colbert et al. [1993] Proc. Natl. Acad. Sci.
      U.S.A. 90:6572-6576) and RA-sensitive transgene expression (Balkan et al. [1992]
      Proc. Natl. Acad. Sci. U.S.A. 89:3347-3351). At E12.5, RA, transgene expression,
      and RAR beta become restricted to the cervical and lumbar cord. RAR alpha,
      CRABPI, and RXR gamma, however, are found throughout the AP extent. CRABPII and
      CRBPI, although expanded within the cervical and lumbar regions, are also found
      throughout the AP axis. Thus, several retinoid signaling molecules continue to be
      expressed beyond distinct regions of the spinal cord where RA is available and
      some RA-responsive genes are either restricted or enhanced. Exogenous RA can
      activate a more widespread response resulting in ectopic transgene and RAR beta
      expression in the thoracic and sacral cord. Not all RA-sensitive genes, however,
      respond; CRABPII and CRBPI expression patterns are unchanged. Finally, not every
      cell within the normal or exogenously induced domains of RA-dependent gene
      expression responds to RA, nor does every cell express RA receptors or binding
      proteins. Thus, regional and cellular differences in the distribution of the
      known retinoid receptors and binding proteins do not predict absolutely where or
      whether retinoid sensitive genes will be expressed or where retinoids will be
      available in the developing spinal cord. Instead, retinoid-mediated gene
      expression in the cervical and lumbar cord seems to reflect retinoid responses
      that rely both on the local availability of retinoids, the identity of the
      responding gene, and an indeterminate array of retinoid signaling molecules.

PMID- 8563021
TI  - Specification of multiple vertebral identities by ectopically expressed Hoxb-8.
AB  - We have recently generated Hoxb-8 gain-of-function mutant embryos, using a Hoxb-8
      transgene driven by a retinoic acid receptor beta 2 promoter to extend the
      expression domain to more anterior regions of the embryo (Charite et al. [1994]
      Cell 78:589-601). Here we describe the phenotype in the axial skeleton of
      transgenic embryos. The severity of the phenotype was variable, and cervical
      vertebrae and the base of the skull were affected in different ways. We observed
      fusion of the anterior arch of the atlas to the dens of the axis, partial
      splitting of the vertebral body and the neural arch of the axis, and abnormal
      morphology of the basioccipital and exoccipital bones. The basioccipital bone
      projected into the atlas, sometimes fusing to the dens of the axis; the
      exoccipitial bones appeared to be transformed towards neural arch-like
      structures. A novel pattern of posterior homeotic transformations was observed,
      involving cervical vertebrae C3 to C7: the ventral aspect of vertebrae C5 to C7
      could acquire different morphologies characteristic of more posterior vertebrae:
      C5 could be transformed into C6, C7, or T1, C6 into C7 or T1, and C7 into T1.
      Phenotypes of different severity could be arranged into a phenotypic series,
      starting with the transformation of C7 to T1 and involving transformation of
      increasingly more anterior vertebrae into increasingly more posterior identities;
      no vertebra acquired a more posterior morphology than that of the vertebra
      immediately caudal to it. Ribs appeared to be formed relatively independently of
      rib heads; cervical ribs (but not rib heads) could be observed as anterior as C3.
      The results suggest that higher levels of ectopically expressed Hoxb-8 result in
      specification of more posterior vertebral identities.

PMID- 8563022
TI  - Developmental defects of the ventromedial hypothalamic nucleus and pituitary
      gonadotroph in the Ftz-F1 disrupted mice.
AB  - Ad4BP (or SF-1) has been identified as a transcription factor which regulates all
      the steroidogenic P450 genes in the peripheral organs, and is encoded by the
      mammalian homologue of Drosophila FTZ-F1 gene. mRNA coding for Ad4BP was detected
      in the hypothalamus and pituitary of rats by RT-PCR. Immunohistochemical analyses
      using an antiserum to Ad4BP in the brain and pituitary revealed that the
      transcription factor is expressed in nuclei of the dorsomedial part of the
      ventromedial hypothalamus (dmVMH) and in some subpopulation of the
      adenohypophysial cells. Double immunostaining of the pituitary for Ad4BP and
      trophic peptide hormones, FSH, TSH, and ACTH, indicated a restricted localization
      of Ad4BP to the gonadotroph. Disruption of the mouse Ftz-F1 gene was clarified to
      induce severe defects in the organization of the dmVMH and the function of the
      pituitary gonadotroph. However, some of the dm VMH neurons and pituitary
      gonadotrophs persisted, which provided a sharp contrast to complete agenesis of
      the peripheral steroidogenic tissues (adrenal and gonads) in the mutant mouse.
      Additional abnormalities were seen in the ventrolateral part of VMH and
      dorsomedial hypothalamic nucleus, both of which do not express Ad4BP but have
      strong reciprocal fiber-connections with the dmVMH. Aromatase P450-containing
      cells in the medial preoptico-amygdaloid region, which were devoid of Ad4BP,
      persisted even in the brain of the gene disrupted mice. The present results
      clearly showed that the hypothalamic and pituitary Ad4BPs are essential to normal
      development of the functional VMH and gonadotroph through some mechanism distinct
      from that in the peripheral steroidogenic tissues.

PMID- 8563023
TI  - Developmental expression of MMP-9 (gelatinase B) mRNA in mouse embryos.
AB  - Considerable remodeling of the extracellular matrix as well as cellular migration
      takes place during embryogenesis. Since the metalloproteinase MMP-9 is implicated
      in these functions in cancer cells, we studied the patterns of expression of MMP
      9 mRNA during the development of post-implantation mouse embryos. MMP-9 mRNA was
      detected using the ribonuclease protection assay in poly A+RNA from 13 to 17 day
      embryos, but not at 11 days. In order to localize these transcripts, in situ
      hybridization was performed on sections of murine embryos from 7.5 to 15 days of
      gestation. At the time of implantation, MMP-9 mRNA was localized to the invading
      trophoblast cells. Strong signals were also seen in the yolk sac. No signal for
      MMP-9 mRNA was seen by in situ hybridization in the embryo until day 11 when
      detectable reaction was seen in the central nervous system. By day 15 strong
      signals were seen in the liver, in the developing bronchial epithelium of the
      lungs and in the primordial alveoli, in the epithelium of the thyroid gland, in
      the thymus, in the endochondrial plates of the bone, and in neural cells. The
      liver from day 15 embryos contained gelatinase activity at 105 kDa consistent
      with MMP-9. Thus, MMP-9 expression appears to be expressed in specific organs in
      a precise temporal sequence during development.

PMID- 8563024
TI  - Developmental pattern of expression of the mouse alpha 1 (XI) collagen gene
      (Col11a1).
AB  - Fibrillar networks are intimately involved in several morphogenetic processes
      which underlie the harmonious development of the vertebrate embryo. Recent
      genetic evidence has demonstrated that the minor types V and XI collagen are key
      regulators of types I and II fibrillogenesis in non-cartilaginous and
      cartilaginous matrices, respectively. A comprehensive understanding of the
      expression and regulation of the genes coding for the chains of the minor
      collagen types is therefore relevant to animal morphogenesis and development. The
      present study was undertaken to elucidate the embryonic pattern of expression of
      the gene coding for the mouse alpha 1 chain of type XI colagen (Col11a1) using
      the technique of in situ hybridization. Transcripts of the Col11a1 gene were
      detected as early as 11 days of gestation. The alpha 1(XI) transcripts were found
      to accumulate mostly in cartilaginous tissues, such as the chondrocranium and the
      developing limbs. Like the major cartilage-specific collagen (type II), Col11a1
      expression was also noted in the neuro-epithelium of the brain. However, alpha
      1(XI) transcripts accumulated in several other non-cartilaginous sites. They
      include odontoblasts, trabecular bones, atrioventricular valve of the heart, the
      tongue, the intestine, and the otic vesicle. Altogether, the data confirm that
      Col11a1 has a broader spectrum of expression than previously thought. This
      finding raises the possibility that the alpha 1(XI) chain may participate in the
      formation of stage- and tissue-specific trimers with distinct functional
      properties.

PMID- 8563026
TI  - Up-regulation of a novel integrin alpha-chain (alpha mt) on human fetal myotubes.
AB  - Integrin expression and distribution was studied in cloned human fetal G6
      myoblasts and myotubes. Immunoprecipitation of beta 1 integrins from surface
      iodinated and metabolically labeled G6 cells typically showed a five-fold
      induction of a beta 1 integrin associated protein upon differentiation. Under non
      reducing conditions this beta 1 associated protein migrated as 145 kD. No such
      beta 1 associated protein was observed in the myogenic L8 rat cell line, before
      or after differentiation. The beta 1 integrin associated cell surface protein
      present in G6 myotubes remained associated with the beta 1 subunit in the
      presence of 1% Triton X-100 and 0.5 M NaCl. Like integrin alpha-chains, the
      protein dissociated from the beta 1 integrin subunit at low pH.
      Immunoprecipitation of G6 myotubes further indicated the presence of alpha 1,
      alpha 3, alpha 5, and alpha v integrins, and small amounts of alpha 4 and alpha 6
      integrins. Immunodepletion with integrin alpha-chain antibodies to alpha 1, alpha
      3, alpha 4, alpha 5, alpha 6, and alpha v integrin chains could not deplete the
      beta 1 integrin associated protein, indicating that it did not interact with any
      of these known integrin heterodimers. Upon treatment with reducing agents, the
      beta 1 integrin associated protein migrated in SDS-PAGE as a 155 kD protein. The
      decreased mobility in SDS-PAGE upon reduction is a feature shared with alpha 1,
      alpha 2, and alpha 9 integrin alpha-chains. Antibodies to alpha 1
      immunoprecipitated an integrin heterodimer distinct from the 155 kD
      protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8563025
TI  - Tissue-nonspecific alkaline phosphatase participates in the establishment and
      growth of feather germs in embryonic chick skin cultures.
AB  - Alkaline phosphatase activity is present in the mesoderm of embryonic chick skin
      and becomes spatially restricted to the dermal condensation of the developing
      feather germs. Inhibitors to tissue-nonspecific (liver/bone/kidney), but not
      intestinal alkaline phosphatase inhibit the establishment and growth of feather
      germs in cultured skins. A window of maximum sensitivity to the inhibitor was
      observed to be the first day of culture when early development and establishment
      of pattern takes place. The cDNA for the avian tissue-nonspecific alkaline
      phosphatase was cloned and sequenced, and Southern analysis revealed a single
      copy of this gene in the avian genome. Northern analysis revealed that a 2.8 kb
      transcript for this form of alkaline phosphatase is present in developing skin.

PMID- 8563027
TI  - CCAAT/enhancer binding protein isoforms expression in the colon of neonatal mice.
AB  - Development of murine proximal colon follows a complex pattern of morphological
      and functional differentiation. Molecular mechanisms and factors responsible for
      colon-specific gene expression remain to be established. In an attempt to
      identify some of these factors, we examined the expression of the alpha, beta,
      and delta isoforms of the CCAAT/enhancer binding protein (C/EBP) transcription
      factor gene family during murine colon development. Whereas C/EBP alpha mRNA
      levels are reduced during the third post-natal week, C/EBP alpha 42 and 30 kD
      proteins levels decrease between post-natal days 8 and 21. C/EBP beta mRNA levels
      increase between post-natal days 4 and 8 and remain constant subsequently, in
      contrast to a decrease in C/EBP beta protein levels between post-natal days 11
      and 15. C/EBP delta mRNA levels increase gradually while C/EBP delta protein
      levels show variations during post-natal development. Changes in C/EBP DNA
      binding activity coincides with modifications in C/EBP isoforms expression. By
      indirect immunofluorescence, we show restriction of C/EBP alpha expression to
      differentiated surface epithelial cells during crypt formation. C/EBP alpha is
      predominantly nuclear with some cytoplasmic staining at all developmental stages.
      C/EBP beta and delta are both predominantly nuclear in crypt and differentiated
      surface epithelial cells, as well as in various cells of the lamina propria and
      muscular layers. Thus, specific C/EBP isoforms are differentially regulated
      during murine colon post-natal development. Differential C/EBP isoforms pattern
      of expression suggests a role for these transcription factors in colon-specific
      gene expression during development.

PMID- 8563028
TI  - Role for platelet-derived growth factor-like and epidermal growth factor-like
      signaling pathways in gastrulation and spiculogenesis in the Lytechinus sea
      urchin embryo.
AB  - The mechanisms underlying sea urchin gastrulation and spiculogenesis have been
      sought for decades. We have identified two growth factor signaling pathways that
      are involved in these developmental events. Antibodies against mammalian platelet
      derived growth factor (PDGF) receptor-beta inhibited gastrulation and
      spiculogenesis, and antibodies against human epidermal growth factor (EGF)
      receptor disrupted gastrulation and spicule placement in Lytechinus pictus and L.
      variegatus embryos. Our studies suggested that the antibodies affect development
      by inhibiting rather than activating the signaling pathways. Polyclonal and
      monoclonal antibodies against the mammalian receptors recognized specifically
      Lytechinus proteins of the expected size of 170-180 x 10(3) M(r). Growth factor
      binding assays indicated that there are approximately 1.25 x 10(4) platelet
      derived growth factor-like receptors per cell at the mesenchyme blastula stage of
      L. pictus, and human platelet-derived growth factor bound with an apparent
      affinity of KD = 4.4 nM to dissociated cells at the mesenchyme blastula stage.
      Immunolabelling experiments showed that at the gastrula stage, the Lytechinus
      platelet-derived growth factor-like receptors are located on the primary
      mesenchyme cells, the gut, and most prominently on the secondary mesenchyme cells
      and the stomodeum. The epidermal growth factor-like receptors stained less
      intensely on the gut and primary and secondary mesenchyme cells. Both receptors
      are expressed on the ciliary band and the gut of the pluteus larva but only the
      PDGF-like receptor is expressed on the primary mesenchyme cells. Pulse studies
      showed that the embryos are sensitive to the platelet-derived growth factor
      receptor-beta and epidermal growth factor receptor antibodies from the blastula
      to sometime between the mesenchyme blastula and midgastrula stages. We show that
      antibodies enter the blastocoel as late as the gastrula stage. Our results
      suggest that platelet-derived growth factor-like and epidermal growth factor-like
      signaling pathways are involved in the early differentiation and morphogenesis of
      the sea urchin gut and spicules.

PMID- 8563029
TI  - Two closely related receptor-type tyrosine phosphatases are differentially
      expressed during rat lung development.
AB  - Transmembrane protein tyrosine phosphatases (PTPases) comprise a newly identified
      class of receptor-like molecules. In most cases their ligands and the substrates
      they dephosphorylate are not known. In order to begin to explore the functions of
      the PTPases in cell physiology and in mammalian development, we examined the
      expression patterns of two closely related receptor-type tyrosine phosphatase
      genes, namely LAR and PTP delta, in fetal rat lung and in selected adult rat
      tissues. In the lung, in situ hybridization and immunohistochemistry show that
      the LAR mRNA and protein are expressed exclusively in the epithelium. In the
      early embryonic or fetal lung (day 13 to 18) LAR is expressed by all of the
      epithelial cells of the forming bronchial tree. This widespread pattern of
      expression is lost later in fetal life (day 21) as the lung matures and acquires
      the morphologic and biochemical features of the adult organ. LAR gene expression
      is then confined to two epithelial progenitor cells of the distal airways, namely
      the bronchiolar Clara cell and the alveolar type II cell. The LAR gene products
      were also found abundantly expressed in epithelial progenitor cells of adult
      esophagus, skin, and small intestine, all of which are continuously renewing
      epithelia. The rat PTP delta gene, on the other hand, is specifically expressed
      in the mesenchyme of the developing lung. The level of the PTP delta mRNA
      decreases as the lung matures. These results suggest that the two closely related
      receptor-type tyrosine phosphatases are differentially expressed in a tissue
      specific fashion. They are expressed mostly in proliferating cells or in cells
      which have potential to proliferate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8563030
TI  - Developmental expression of H-2K major histocompatibility complex class I
      transgenes requires the presence of proximal introns.
AB  - The pattern of expression of the H-2K major histocompatibility complex (MHC)
      class I gene is complex. During embryonic development H-2K mRNA, detectable from
      midgestation, is poorly expressed. In the adult, H-2K expression is nearly
      ubiquitous but transcriptional regulation occurs leading to different mRNA levels
      in the different organs of the mouse. In vitro studies have shown that most of
      the regulatory elements controlling H-2K gene transcription are located in the 5'
      region of the gene. However, using fusion transgenes in which reporter genes were
      under the control of 2 kb of H-2K 5' regulatory region, we have previously shown
      that this region was not sufficient to ensure correct developmental transgene
      expression. By contrast, a native 9.25 kb H-2K transgene was expressed
      appropriately both in the adult and in the embryo. In order to localise more
      precisely the cis-acting regulatory sequences involved in H-2K developmental
      expression, we have now constructed new transgenic lines containing H-2Kb
      transgenes that were deleted from specific parts of the H-2Kb gene. We show that
      deletion of either the H-2K 3' flanking region or the 5 (out of 7) distal introns
      results in an expression of the transgenes which is similar to that of the
      endogenous H-2K gene, both in the adult and during embryonic development. By
      contrast, deletion of all the introns or of the two proximal ones abrogates H-2K
      transgene expression. Our data reveal the complexity of H-2K regulation and
      highlight the crucial role of proximal introns in H-2K expression in the living
      organism.

PMID- 8563031
TI  - Preparation of bovine tracheal smooth muscle for in vitro pharmacological
      studies.
AB  - In this study a new method is described for standardization of both length and
      weight of bovine tracheal smooth muscle strips to be used for measuring airway
      responsiveness in vitro. Tracheal smooth muscle was cut into strips 2.5-mm thick
      and 10-mm long with an average wet weight of 25.9 +/- 0.6 mg (n = 5). By use of
      preloads varying from 0.5 to 10 g, it was found that 5 g caused the highest
      contraction and relaxation of the tissues in response to pharmacological agents.
      Moreover, at a preload of 5 g the variations among the maximal responses induced
      by histamine, methacholine, KCl, and salbutamol were very small (standard errors
      being 6.8%, 5.0%, 2.5%, and 1.6% of the corresponding average maximal response)
      as well as were the variations in the pD2 values.

PMID- 8563032
TI  - A model of isoniazid-induced hepatotoxicity in rabbits.
AB  - Isoniazid (INH) continues to be an effective drug used for chemoprophylaxis and
      treatment of tuberculosis. Unfortunately, INH is associated with significant
      hepatotoxicity in up to 2% of individuals exposed, and if this adverse event is
      not recognized early it can be fatal. Research on INH-induced hepatotoxicity has
      been hampered by the lack of a suitable animal model that closely resembles the
      toxicity in humans. The mechanism of INH-induced hepatotoxicity is still unknown.
      The present study describes the development of a reliable model of INH-induced
      hepatotoxicity in rabbits. The protocol involves repeated injections of INH over
      a 2-day period, resulting in significant hepatic necrosis as indicated by
      elevations of plasma argininosuccinic acid lyase activity. Pretreatment with
      phenobarbital increased the occurrence of INH-induced hepatic necrosis from
      approximately 60% (9 out of 15 rabbits) with INH alone to more than 90% (13 out
      of 14 rabbits). Morphological indices were used to demonstrate the presence of
      INH-induced hepatotoxicity, and biochemical indices were used to demonstrate both
      the presence and severity of INH-induced hepatotoxicity in this model. This model
      may prove useful for further investigations into the mechanism of INH-induced
      hepatotoxicity.

PMID- 8563033
TI  - Analysis of the enantiomers of 3,4-methylenedioxy-N-ethylamphetamine (MDE, "Eve")
      and its metabolite 3,4-methylenedioxyamphetamine (MDA) in rat brain.
AB  - The methylenedioxy analogues of amphetamine are used recreationally despite
      concerns raised regarding potential neurotoxicity of the parent compounds and a
      number of metabolites. Much has been written regarding 3,4
      methylenedioxymethamphetamine (MDMA; 3,4-methylenedioxy-N-ethylamphetamine (MDE;
      "Eve"), despite recent reports indicating the abuse of this drug and its
      potentially serious side effects. An assay procedure was developed for the
      simultaneous quantitation of both enantiomers of MDE and its metabolite MDA; the
      method involves derivatization with an optically pure reagent and analysis on a
      gas chromatograph equipped with a capillary column and a nitrogen-phosphorus
      detector. Brain levels of the enantiomers of MDE and MDA were examined in the rat
      at different time periods after acute i.p. injections of racemic MDE and the
      results were compared with levels of MDMA and MDA obtained after i.p. injection
      of MDMA in a previous study from our laboratories. The levels of the enantiomers
      of MDE and MDA achieved at 1, 4, and 8 hr were lower than in the case of MDMA.
      Stereoselective differences in brain levels of enantiomers of the parent drug and
      metabolite were much less marked with MDE than with MDMA, but where these small
      differences did exist in the case of MDE, the (R)-(-) vs (S)-(+) relationship was
      opposite to that reported for MDMA.

PMID- 8563034
TI  - A new technique for continuous measurement and recording of gastric potential
      difference in the rat: evaluation of NSAID-induced gastric mucosal damage.
AB  - Disruption of the gastric mucosal barrier by the so-called "barrier breakers"
      such as ethanol, aspirin, and bile is associated with an increase in gastric
      potential difference (GPD), that is, a decrease in its negativity. Because a good
      correlation between the degree of histological damage and changes in GPD has been
      observed, this parameter has been used increasingly as an index of mucosal
      integrity. However, the current methodology for measuring GPD is laborious due to
      the preparation and checking of KCl-agarose bridges prior to each experiment, and
      calculations--usually handmade--are time-consuming and inaccurate. In this paper,
      a new method allowing simultaneous measurement and recording of GPD in the rat is
      described. The method allows a simultaneous recording of intragastric pH and an
      automatic data analysis. The new technique has been validated by studying mucosal
      damage induced by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs)
      (namely indomethacin and droxicam) as well as the mucosal protective activity of
      an antacid and sucralfate. The similarity between the results obtained in this
      rat model and those derived from human experiments clearly show that the
      developed methodology yields results that are predictive for human pharmacology.

PMID- 8563035
TI  - Only controls: effect of handling, sham injection, and intraperitoneal injection
      of saline on behavior of mice in an elevated plus-maze.
AB  - In male NIH-Swiss mice intraperitoneal injection of physiological saline
      significantly diminished (vs. naive mice) the ratio of the number of entries into
      open arms over the sum of entries into open and closed arms, and significantly
      prolonged time spent in closed arms. These two effects are considered to be
      typical for anxiety-inducing drugs (anxiogens). The time spent in open arms and
      at the intersection was unaffected. An equal number of entries into closed and
      also open arms was observed among fast- and slow-moving individuals. This is an
      argument against using the number of entries into arms as a measure of locomotor
      activity of mice. Additional measurement of locomotor activity in actometers is
      needed to check whether drugs used in experiments with elevated plus-maze alter
      locomotor activity. Injection of saline significantly shortened the latency of
      reaching one of the closed arms from the free end of an open arm. Handling, sham
      injection, and injection significantly diminished the shortening of latency in a
      second experiment (vs the latency in the first one), a parameter used as a
      criterion of memory and learning. Thus, saline-treated groups taken as controls
      in pharmacological experiments possess the behavioral profile of stressed and
      anxious animals in an elevated plus-maze, a device used as a model of anxiety and
      a model for studying memory and learning in mice and rats.

PMID- 8563036
TI  - On the true affinity of glycine for its binding site at the NMDA receptor
      complex.
AB  - To determine the exact potency of inhibitors acting at the glycine site of the
      NMDA receptor complex using [3H]glycine as a radioligand, the true equilibrium
      constant (KD) of the radioligand has to be known. To achieve this goal, (1) the
      contamination of water by glycine was studied, (2) the true affinity of glycine
      for the NMDA receptor was estimated by different methods, and (3) the inhibition
      constant of a number of antagonists was determined. HPLC analysis of the
      deionized water used for the preparation of the assay buffers and solutions
      resulted in glycine concentrations below 6 nmol/L in four out of seven samples
      analyzed. The observable equilibrium constant of [3H]glycine binding (Kobs) was
      found to vary, in the presence of 10-mumol glutamate per liter, between 36 and
      163 nmol/L (mean +/- SD: 69 +/- 21 nmol/L, 140 determinations). Based on the
      observation that the polyamine spermine increased the potency of glycine, but not
      that of glycine antagonists, an algorithm was developed to calculate KD from Kobs
      and IC50-values obtained with and without 100-mumol spermine per liter. Using
      four different antagonists, KD-values between 24 and 57 nmol/L were obtained.
      Computer analysis of glycine-stimulated [3H]MK-801 binding resulted in EC50
      values between 22 and 35 nmol/L. Based on these results, a true affinity constant
      for [3H]glycine of 40 nmol/L was assumed and used for the determination of Ki
      values of 15 different inhibitors of [3H]glycine binding.

PMID- 8563037
TI  - Preparation and characterization of anti-peptide antibodies directed against
      human phenol and hydroxysteroid sulphotransferases.
AB  - Sulphotransferases (STs) catalyze the sulphation and, in general, detoxication of
      a large number of xenobiotics and endogenous compounds. A total of six synthetic
      peptides derived from the cDNA-derived amino acid sequences of the human phenol
      sulphating form of phenosulphotransferase (P-PST) and human hydroxysteroid
      sulphotransferase (HST)--three from each sequence--were separately conjugated to
      the carrier protein keyhole limpet hemocyanin, and used to immunize rabbits. One
      successful antibody preparation was produced from among the P-PST peptides, and
      two from the HST peptides. On immunoblot analysis following SDS/PAGE, the anti-P
      PST antibodies recognized two major forms of phenol ST in man, P-PST and the
      monoamine-sulphating form of PST, M-PST, and the two antibody preparations
      against HST recognized the human HST. These experiments demonstrate that it is
      possible to design specific antibodies against human sulphotransferases based on
      their amino acid sequences.

PMID- 8563038
TI  - Collagen degradation within subcutaneous air pouches in vivo: the effects of
      proteinase inhibitors.
AB  - A straightforward in vivo model of collagen degradation is described that can be
      used to measure the effects of different classes of proteinase inhibitors. Air
      pouches, formed subcutaneously in the dorsal thoracic region of rats, were
      inflamed 6 to 8 days later by injecting lambda-type carrageenan. 14C-Collagen was
      injected into the air pouches either 1 day before or 1 day after lambda
      carrageenan-induced inflammation: in the latter case, the inflammatory exudate
      fluid was drained from the air pouches immediately prior to administering 14C
      collagen. Ninety percent of the 14C-collagen was degraded and cleared within 3
      days from pre-inflamed air pouches, but degradation was much slower from the post
      inflamed or non-inflamed air pouches. Proteinase inhibitors injected
      simultaneously with the 14C-collagen, and again 6 hr later, reduced the extent of
      14C-collagen degradation from air pouches measured after 24 hr. Forty-two percent
      of the degradation of 14C-collagen could be inhibited by a mixture of enzyme
      inhibitors (leupeptin, alpha 1-anti-proteinase, aprotinin, and pepstatin)
      injected together with 1,10 phenanthroline, the zinc metalloenzyme inhibitor. The
      1,10 phenanthroline alone caused a 33% inhibition of 14C-collagen degradation,
      and the inhibitor mixture given alone inhibited 14C-collagen loss by 25%.
      Approximately 60% of the degradation of 14C-collagen in this model was mediated
      by mechanisms resistant to this combination of proteinase inhibitors, which may
      indicate the significant involvement of non-enzymic modalities, or degradation in
      intracellular compartments inaccessible to extracellular agents.

PMID- 8563039
TI  - Macro, micro, and molecular research on spermatogenesis: the quest to understand
      its control.
AB  - Synchronous maturation of the germ cells in the seminiferous epithelium has long
      been recognized by microscopy, and is believed to be a consequence of a complex
      interaction between the germ cells and the Sertoli cells, largely driven by
      testosterone and its synergistic action with follicle-stimulating hormone.
      Overall coordination of the cycle of the seminiferous epithelium is reviewed with
      regard to the known and possible actions of testosterone upon the Sertoli cells
      and the germ cells. With gradual refinements of optical instrumentation and
      development of a wide range of histological, morphometric, biochemical, and
      molecular techniques, coupled with selective alterations of hormonal stimulation
      and the cellular composition of the testis, new approaches to the question of how
      sperm production is regulated are becoming available. Germ cell and Sertoli cell
      functions are intimately related to each other via local, intratesticular or
      paracrine signals which are suppressed or triggered at certain defined steps in
      the spermatogenic process. The coordination of germ cell proliferation and
      maturation is discussed in terms of the contributions made by microscopical
      techniques.

PMID- 8563040
TI  - Efficiency of spermatogenesis.
AB  - Spermatogenesis is a process of division and differentiation by which spermatozoa
      are produced in seminiferous tubules. A measure of efficiency of spermatogenesis
      is the estimated number of spermatozoa produced per day per gram of testicular
      parenchyma. This measure is not influenced by species differences in testicular
      size; however, it is influenced by species differences in the numerical density
      of germ cells and in the life spans of these cells. Seminiferous tubules are
      composed of somatic cells (myoid cells and Sertoli cells), and germ cells
      (spermatogonia, spermatocytes, and spermatids). Activity of these three germ
      cells divide spermatogenesis into spermatocytogenesis, meiosis, and
      spermiogenesis, respectively. Spermatocytegenesis involves mitotic cell division
      to increase the yield of spermatogenesis and to produce stem cells and primary
      spermatocytes. Meiosis involves duplication and exchange of genetic material and
      two cell divisions that reduce the chromosome number and yield four spermatids.
      Spermiogenesis is the differentiation of spherical spermatids into mature
      spermatids which are released at the luminal free surface as spermatozoa. The
      spermatogenic cycle is superimposed on the three major divisions of
      spermatogenesis. Spermatogenesis and germ cell degeneration can be quantified
      from numbers of germ cells in various steps of development throughout
      spermatogenesis, and quantitative measures are related to number of spermatozoa
      in the ejaculate. Germ cell degeneration occurs throughout spermatogenesis;
      however, the greatest impact occurs during spermatocytogenesis and meiosis.
      Efficiency of spermatogenesis is related to the amount of germ cell degeneration,
      pubertal development, season of the year, and aging of humans and animals. Number
      of Sertoli cells and amount of smooth endoplasmic reticulum of Leydig cells (but
      not Leydig cell number) are related to efficiency of spermatogenesis. In humans,
      efficiency of spermatogenesis is reflected in number of spermatogenic stages per
      cross-section and number of missing generations within each stage; however, the
      arrangement of stages along the tubular length does not reflect differences in
      the efficiency of spermatogenesis. In short, spermatogenesis involves both
      mitotic and meiotic cell divisions and an unsurpassed example of cell
      differentiation in the production of the spermatozoon, and daily sperm production
      per g parenchyma is a measure of its efficiency.

PMID- 8563041
TI  - Theory and practice of stereological techniques applied to the estimation of cell
      number and nuclear volume in the testis.
AB  - The historical background to contemporary approaches to the estimation of
      cell/nuclear number and volume in the testes is reviewed. The limitations of
      older geometric model-based approaches to the estimation of cell/nuclear number
      are discussed, and the need for absolute estimates of cell number rather than
      ratio estimates is examined. The physical and optical disector approaches to the
      direct estimation of numerical density and, hence, absolute cell number are
      presented together with data illustrating their operational efficiency in the
      testis. New approaches to the direct estimation of nuclear/cell volume, using the
      point-sampled intercept family of methods, are presented and illustrated, using
      the example of the Sertoli cell nucleus. The use of both classical transverse and
      the newer vertical section approaches is explored. Estimation of Sertoli
      cell/nuclear volume in the volume (point-sampled intercept procedure) and number
      (nucleator and rotator methods) distributions on both conventional transverse and
      vertical sections is discussed. The use of transverse sections of the testis is
      shown to produce a consistent bias in the estimation of Sertoli cell nuclear
      volume in 120-day-old animals, with all the estimators. Comparison of the Sertoli
      cell nuclear volume (measured on vertical sections) in the volume and number
      weighted distribution suggests a coefficient of variation of volume in the number
      distribution of 0.4-0.5, suggesting either a random or stage-dependent variation
      in Sertoli cell nuclear size which requires further exploration.

PMID- 8563043
TI  - A transmission electron microscope (TEM) calibration standard sample for all
      magnification, camera constant, and image/diffraction pattern rotation
      calibrations.
AB  - A calibration sample for transmission electron microscopy (TEM) has been
      developed that performs the three major instrument calibrations for a
      transmission electron microscope: the image magnification calibration for
      measurements of images, the camera constant calibration for indexing diffraction
      patterns, and the image/diffraction pattern rotation calibration for relating
      crystal directions to features in the image. This offers an improvement over
      commercially available calibration standards, where up to five different samples
      are required to perform these three calibrations. The new calibration sample
      consists of an electron-transparent cross-sectional TEM sample made from a
      molecular beam epitaxy (MBE)-grown, single-crystal semiconductor wafer. When the
      calibration structure is viewed in a TEM, it appears as a series of light and
      dark layers where the layer thicknesses are very accurately known. The calibrated
      thickness measurements of these light (silicon) and dark (SiGe alloy) layers are
      based on careful TEM measurements of the [111] lattice spacing of silicon which
      is visible on the calibration sample itself, and are supported by X-ray
      diffraction measurements. Furthermore, the layer thickness variation across the
      entire silicon wafer has been verified to be less than 1%, allowing all samples
      prepared from the same wafer to have errors in the given layer thickness values
      of less than 1%. As the sample is a single crystal of silicon, the calibrations
      requiring electron diffraction information such as the camera constant
      calibration and the image/diffraction pattern rotation calibration can also be
      performed easily and unambiguously. One single calibration sample can therefore
      be used to provide all three of the major TEM instrument calibrations at all
      magnifications and all camera lengths.

PMID- 8563042
TI  - Effects of extracellular matrix on differentiation of mouse fetal gonads in the
      absence of mesonephros in vitro.
AB  - The influence of mesonephric tissues and the extracellular matrix on mouse
      gonadal differentiation was examined in vitro. Gonadal ridges, with or without
      the adjacent mesonephric region, were removed from mouse embryos on day 12 post
      coitum (p.c.), and cultured in the presence or absence of reconstituted basement
      membrane (matrigel) for 5 days. Culturing control undifferentiated testes with
      mesonephric tissues induced normal testicular differentiation. When testes
      without mesonephric tissues were cultured in the absence of matrigel, testicular
      cord formation was not observed in the explants. Sertoli cells were irregularly
      arranged in the testicular parenchyma, and no continuous basal lamina was formed
      around the Sertoli cells. However, when testes without mesonephric tissues were
      embedded in matrigel and cultured for 5 days, the Sertoli cells were organized
      into testicular cord-like structures. The Sertoli cells positioned at the base of
      the cord-like structures were closely connected to the matrigel at their basal
      surface, and showed a polarized distribution of vimentin filaments in their basal
      cytoplasm. Leydig cells, on the other hand, were differentiated in all testicular
      explants. In all ovarian explants, germ cells normally entered meiotic prophase.
      Therefore, these findings indicate that the extracellular matrix permits
      testicular differentiation in the absence of the mesonephros, and that removal of
      mesonephric tissues leads to developmental failure of cord formation because the
      components of the extracellular matrix around pre-Sertoli cells are incomplete.

PMID- 8563044
TI  - A simple modification to the Fischione jet polishing holder to reduce the
      deformation of thin samples.

PMID- 8563045
TI  - A specimen holder for high-resolution low-temperature scanning electron
      microscopy.

PMID- 8563046
TI  - Bacteriology of Helicobacter pylori.
AB  - The discovery and first isolation of H. pylori in pure culture from gastric
      biopsies in 1982 provided the basis for a completely new area of microbiology.
      Since then, H. pylori has been an intensively pursued topic world-wide, and
      extensive data have been acquired on all aspects of its basic microbiology, both
      at the conventional phenotypic level and at the molecular level. H. pylori is a
      remarkable microorganism because of its ability to readily colonize a major
      proportion of human population worldwide and to persist successfully for long
      periods (probably decades) in a hostile environment. At the same time it
      interacts with the host immune system in such a way as to permit long-term
      survival. Blaser (1993) proposed a model in which both host and parasite adapt to
      down regulate inflammatory phenomena to promote survival. Urease production by H.
      pylori (an important factor in that process) is one of its most distinct features
      with a key role in its success as an infective agent. Another less obvious yet
      highly significant feature of H. pylori is the ability to achieve a high degree
      of interstrain diversity in genomic DNA nucleotide sequences, while maintaining
      overall genetic homology and phenotypic homogeneity amongst strains. The
      selective advantage this diversity provides the bacterium is not understood. A
      key objective of future microbiological studies should be to understand the
      population genetic structure of H. pylori. Most species of bacteria are clonal in
      natural population structure, yet all genomic data suggest the contrary is true
      for H. pylori. Furthermore, it is not clear if all strains of H. pylori are
      equally pathogenic, and that some subsets may possess additional pathogenicity
      factors that are responsible for the development of different disease
      pathologies. A phylogenetic framework of the genetic relationships of the clones
      within H. pylori would enable an examination of the total genetic diversity, with
      respect to ethnic or geographical population and the nature of the disease
      caused. A second aim would be to understand the mode of transmission of H. pylori
      from individual to individual. Although there is some evidence for either an oral
      oral or a faecal-oral route, no reliable microbiological protocols exist for the
      isolation of H. pylori from non-gastric sites. There is therefore, considerable
      scope for the development of microbiological media and test methods for isolation
      from faeces and dental plaque, and possibly even food and environmental sources.
      To conclude, the availability of new information on the above aspects would
      greatly facilitate the monitoring of therapy; would enable more accurate
      epidemiological studies on the age of acquisition and spread of H. pylori
      infection; and would provide a basis for future prevention of disease by
      identification of individuals at high risk of infection with a particular
      pathogenic strain type.

PMID- 8563047
TI  - Prevention of Helicobacter pylori infection.
AB  - A gastroenterologist, treating a patient with H. pylori, must decide whether the
      unit of treatment is only the ill individual, or the family, perhaps including
      close contacts. If it is the family and close contacts, is it all family members
      and contacts, or are there some ages, relationships, or clinical characteristics
      that increase the risk of transmission to the patient after successful treatment
      of their infection? In preventing reinfection, the available data suggest: the
      natural infectious dose has not been determined infection may occur from oral or
      faecal shedding children are more infectious than adults socio-economic factors
      are important in any comparison of infection rates food and water seem unlikely
      vehicles in the developed world travel in the third world may increase risk of
      infection seropositivity in adults predominantly reflects exposure in childhood
      infection is frequently with more than one strain reinfections are not more
      frequent in families with other members infected reinfections are infrequent with
      strains different from the original strain reinfection might be more frequent in
      developing countries no need for all family members to be treated to reduce
      reinfection rates. In considering vaccine, the available data suggest: breast
      milk IgA can reduce infection rate antibodies induced by vaccine may reduce
      infection in animals late benefit of childhood vaccination in developed countries
      probable early benefit of childhood vaccination in developing countries
      vaccination of already infected adults would have cost-benefit.

PMID- 8563048
TI  - Histological responses to Helicobacter pylori infection: gastritis, atrophy and
      preneoplasia.
AB  - It is interesting that the principal histological features of acute H. pylori
      gastritis, surface epithelial degeneration and neutrophil polymorph infiltration,
      remain as the most sensitive indicators of the 'activity' of infection in the
      chronic phase. It is not surprising therefore that these are the first features
      to resolve after successful H. pylori eradication therapy. In one of the earliest
      studies of histological response to eradication, McNulty et al (1986) endoscoped
      patients immediately after a three-week treatment regime and found a highly
      significant decline in polymorph scores. The response was even more striking four
      weeks after the end of treatment, as at that time biopsies from responders were
      virtually devoid of polymorphs (Valle et al, 1991). Indeed the disappearance of
      polymorphs from a post-treatment biopsy is a useful indicator of successful
      eradication. Less attention has been paid to the recovery of the surface
      epithelium yet this is an impressive feature when comparing pre- and post
      treatment biopsies. Using subjective grading of surface epithelial lesions,
      Solcia et al (1994) found a dramatic and highly significant improvement in mean
      grade immediately after anti-H. pylori treatment. Recently a morphometric
      approach was used to demonstrate a significant increase in surface epithelial
      cell height corresponding to the recovery that accompanies successful H. pylori
      eradication (Hassan et al, 1993). Chronic inflammatory cell infiltrate resolution
      is much slower. There is only a gradual reduction in cell density so that even 6
      months after eradication treatment the mean score had only fallen by 50% of pre
      treatment values (Solcia et al, 1994). In the author's experience, a minor
      increase in such cells persists for many months and may never completely resolve,
      in that more lymphocytes and plasma cells are seen than in a truly normal (pre
      infection) stomach. Valle et al (1991) found resolution of chronic inflammation
      in only 15% of subjects at 6 months and in 51% at one year after eradication. The
      long delay in disappearance of lymphocytes and plasma cells poses a question over
      continuing antigenic stimulation in the absence of infection. Possible answers
      could involve persistence of antigenic moieties in dendritic cells of the lamina
      propria, or sensitization to host antigens brought about by infection so that an
      element of autoimmunity persists after eradication. Unravelling these mechanisms
      will add important new elements to our understanding of the long-term
      consequences of this fascinating infection.

PMID- 8563049
TI  - Pathogenic mechanisms.
AB  - Research is asking how H. pylori causes diseases, and also why the same bacteria
      produces different conditions in different persons. The process involves
      bacterial factors and the host's response. Some bacterial factors such as urease
      are produced by all strains of H. pylori. This enzyme may damage the gastric
      epithelium by practically releasing ammonia. Other bacterial factors such as
      vacuolating toxin are only produced by some strains, and these strains are more
      likely to cause ulcers or cancer. The host's response has been studied by
      physiologists, immunologists, and histologists, but the separation of systems is
      artificial. For example, physiologists find that H. pylori stops gastric D-cells
      from expressing somatostatin normally, which impairs reflex inhibition of acid
      secretion, but the D-cell malfunction is probably due to inflammatory factors. In
      H. pylori gastritis, the gastric epithelial cells behave like immunocytes and
      express class II molecules and cytokines such as interleukin-8. The patient's
      histological response to H. pylori is quite closely related to the disease
      outcome. Patients who respond by developing gastric atrophy are more likely to
      get gastric ulcers or stomach cancer, but patients whose gastric corpus remains
      healthy tend to secrete more acid and develop duodenal ulcers, particularly if
      they have gastric metaplasia in their duodenum. Studies of disease mechanisms
      provide a valuable insight into the development of these common diseases, and may
      enable us to identify at-risk groups who particularly merit eradication therapy.

PMID- 8563050
TI  - Diagnosis of Helicobacter pylori.
AB  - Several techniques have been proposed to diagnose H. pylori infection based
      either on the direct or indirect detection of the bacteria. [table: see text] The
      current direct methods are performed on biopsy specimens obtained at endoscopy.
      Histological examination must always be performed because in addition to H.
      pylori detection it allows observation of the lesions present. Culture, while
      more demanding in terms of transport conditions, is a sensitive technique which
      is worthwhile when the patient might be treated with antibiotics to which the
      bacteria may be resistant. PCR has been more recently introduced and exhibits a
      good sensitivity and specificity. Rapid tests, such as the rapid urease test and
      examination of a Gram stained biopsy smear, are convenient and cheap but of lower
      sensitivity. Indirect methods are based either on the serological IgG response or
      the labelled urea breath test. Both are sensitive. The breath test is especially
      adapted to post-treatment control while serology is of interest for screening
      patients and epidemiological studies. New techniques have recently been proposed
      but are not yet applicable to routine diagnosis: detection of H. pylori in faeces
      by culture or PCR; detection of IgG antibodies in saliva or urine.

PMID- 8563051
TI  - Helicobacter pylori in children.
AB  - Helicobacter pylori is the major cause of antral gastritis in children, however,
      it is not always associated with symptoms. The exception to this occurs in
      duodenal ulcer disease with which H. pylori is linked in children albeit less
      strongly than in adults. Duodenal ulcers do not recur in older children following
      eradication of H. pylori. The importance of asymptomatic carriage of H. pylori in
      children, particularly in relation to the duration of this infection and the
      subsequent development of gastric cancer, remain to be established. Helicobacter
      pylori is associated with both hypochlorhydria and persistent diarrhoea in
      children in developing countries, but the significance of this association is
      still unknown. Although there is no consensus on the optimal regimen for treating
      H. pylori infection in children, dual therapy with amoxycillin and bismuth
      subcitrate for 2 weeks followed by monotherapy with bismuth subcitrate for a
      further 6 weeks will eradicate H. pylori infection in the majority of children.
      Those who relapse may be treated with a repeat course plus metronidazole for 4
      weeks. Compliance with such regimens is a problem and shorter treatment courses
      that are equally effective in children need to be defined. Similarly, studies are
      required on the influence of the intrafamilial reservoir of H. pylori infection
      on relapse after treatment and the need for whole family eradication therapy.

PMID- 8563052
TI  - Helicobacter pylori in duodenal and gastric ulcer disease.
AB  - The decision to treat a patient should in general always be based on potential
      risk and advantage. Widespread and uncontrolled use of all kinds of anti-H.
      pylori regimens may promote development of antimicrobial resistant strains. In
      particular, antimicrobial monotherapy is associated with failure to eradicate H.
      pylori and induction of resistant strains. Polychemotherapy is much more
      effective and has a lower risk for development of antimicrobial resistant H.
      pylori strains but carries the risk of significant drug-related side effects. If
      the prescribed anti-H. pylori regimen is not effective in at least 80%, or if the
      patient is not compliant, this type of therapy should not be considered. Also if
      reinfection is to be expected, the risk may outweigh potential benefits (Graham,
      1993). Guidelines published in 1990 by an international working party during the
      World Congress of Gastroenterology recommended H. pylori eradication only in
      patients where duodenal ulcer was a serious management problem requiring lifelong
      maintenance therapy, and in whom complications (bleeding, perforation) had
      occurred or surgery was considered (Tytgat et al, 1990). Recently less stringent
      guidelines were recommended. A National Institutes of Health (NIH) Consensus
      Development Conference has recommended that all patients with gastric or duodenal
      ulcer who are H. pylori infected should be treated with antimicrobials including
      patients presenting with an ulcer for the first time. In addition, patients on
      maintenance antisecretory medication should also be contacted and treated for H.
      pylori infection (Anonymous, 1994). The ulcer relapse rate during prolonged
      follow-up after H. pylori eradication is very low. Despite this, it is advised
      that antisecretory medication is continued after successful H. pylori eradication
      in patients with previous ulcer complications. In all other patients maintenance
      antisecretory medication can be stopped after successful eradication. It is not
      known whether H. pylori eradication lowers the risk of NSAID-induced ulceration
      or whether the risk of ulcer complications is reduced.

PMID- 8563053
TI  - Nature of non-ulcer dyspepsia and related conditions.
AB  - To date, the precise role of Helicobacter pylori in the pathogenesis of NUD
      remains uncertain. There is some evidence to suggest that the organism is
      implicated in specific subgroups (mostly the ulcer-like form), but it is not
      enough for any firm conclusions to be drawn as to the importance of the bacterium
      as a cause of dyspeptic symptoms or as to the efficacy of anti-infective regimens
      in the treatment of NUD. Large, well-designed prospective studies with a long
      term follow-up are needed to establish which subgroups of dyspeptic patients may
      benefit most from eradication of H. pylori.

PMID- 8563054
TI  - Helicobacter pylori as a risk factor for cancer.
AB  - In 1985, gastric cancer was the second most common cause of cancer death in the
      world. The rapid decline in gastric cancer rates over the last few decades has
      been attributed to a decline in the prevalence of environmental risk factors for
      gastric cancer and/or an increase in the prevalence of protective factors. One
      such risk factor could be the bacterium Helicobacter pylori. Epidemiological
      studies have shown that areas with high gastric cancer rates often have a
      correspondingly high prevalence of H. pylori and prospective studies have shown
      that subjects with serological evidence of H. pylori infection were significantly
      more likely to go on to develop gastric cancer than those who did not.
      Helicobacter pylori itself does not appear to be either genotoxic or mutagenic.
      Infection is, however, associated with increased cell turnover, a chronic immune
      response accompanied by increased levels of reactive oxygen metabolites and a
      reduction in gastric levels of ascorbic acid, all conditions that could favour
      the development of cancer. Nonetheless, the majority of those who are infected
      with H. pylori do not go on to develop gastric cancer and other factors, such as
      the strain of the infecting organism or consumption of dietary antioxidants
      including vitamin C, could also affect the risk of cancer. Finally, it has been
      estimated that more than one third, and possibly as many as 90% of gastric
      cancers might be attributable to infection with H. pylori. Prevention and
      treatment of infection are, therefore, possible approaches to reducing gastric
      cancer rates. It is, however, unclear what, if any, effect eradication of the
      infection would have on an individual's risk of gastric cancer and, to date, anti
      Helicobacter therapy has only been shown to be of potential benefit in the
      treatment of low grade gastric MALT lymphomas.

PMID- 8563055
TI  - Eradication of Helicobacter pylori.
AB  - Although there are numerous publications reporting eradication results, the
      general picture is confused by the bewildering multiplicity of treatment
      schedules employed by the various workers. The over-riding need now is for large
      scale trials, and more especially for direct comparisons of different treatment
      regimens in the same populations of patients. Such data are entirely absent from
      the literature at present. Standardization of definitions and of methodology
      pertaining to diagnosis of eradication, recording of side effects, measurement of
      compliance and determination of recurrence or of reinfection, is badly needed. As
      the definition of eradication remains arbitrary, it is important to include
      genome fingerprinting techniques in the long-term follow-up for recurrence, so
      that the question of reinfection versus recrudescence can be examined (Bell et
      al, 1993b; Xia et al, 1994). Because of the wide differences in the agents used
      in H. pylori eradication therapies, proper double-blinding of treatment trials
      remains a difficult problem. This can be dealt with to some extent by ensuring
      that the interpretation of tests for H. pylori eradication is performed by
      personnel unaware of the clinical details. Review of the existing data on
      eradication of H. pylori indicates that clinically useful results can be achieved
      in some 70 to 95% of patients, on an intention to treat basis. Compliance, side
      effects and resistance to metronidazole remain the limiting factors. Efficacy,
      freedom from side effects, simplicity and low cost will determine the success of
      any regimen in the future. At present, it is not possible to make firm
      recommendations in favour of one regimen over another, but it seems reasonable to
      forecast that dual therapies consisting of a PPI and an antibiotic will receive
      much attention. Preparations consisting of an H2RA associated with a bismuth
      compound, which are used together with an antibiotic are an interesting approach.
      Compliance should be as good as with a normal dual therapy and the eradication
      results look promising (Wyeth et al, 1994; Webb et al, 1994). The advantages of
      dual therapies that include a PPI lie in their simplicity, in not relying on
      imidazole for their anti-H. pylori effect but on the profound inhibition of acid
      output produced by the PPI. Thus PPI based dual therapy can probably evoke better
      compliance than the more complicated regimens. The use of PPIs has other
      advantages in addition to decreasing the MIC90 of the antibiotic combined with
      it. This is because administration of a powerful inhibitor of gastric acid
      secretion, such as a PPI, will aid the rapid healing of an ulcer crater and will
      rapidly relieve the symptoms of peptic ulceration. Gastrin releasing peptide
      stimulated acid secretion is raised in duodenal ulcer patients to approximately
      sixfold over control levels according to El-Omar et al (1993b), and although it
      returns to normal following the eradication of H. pylori, this process takes time
      to become effective (El-Omar et al, 1993a). Suppression of acid output provides
      an immediate therapeutic shield, while the decrease in inflammation and acid
      output secondary to H. pylori eradication can be established. The most widespread
      resistance to antibiotics exhibited by H. pylori is with respect to imidazoles.
      The prevalence of metronidazole resistance is widespread in the emergent
      countries (Glupczynski et al, 1990), but it is also appreciable in the West,
      especially in women, who may have been given metronidazole in the treatment of
      pelvic infections (Rautelin et al, 1992; Banatvala et al, 1994). Moreover, H.
      pylori becomes resistant to metronidazole very easily and often as a result of
      treatment which includes an imidazole compound (Malfertheiner, 1993; Banatavala
      et al, 1994). On the other hand, H. pylori resistance to macrolides is not
      widespread and does not develop easily during their administration. It is
      difficult to forecast which antibiotic will be the most widely used agent

PMID- 8563057
TI  - [Intestinal motility after massive small bowel resection].
AB  - To evaluate intestinal motility after 80% massive distal small bowel resection
      (MSBR), we continuously monitored interdigestive and postprandial bowel motility
      using bipolar electrodes and/or contractile strain gage force transducers in
      conscious beagle dogs before, and at 0-4 weeks and 8-13 months after the surgery.
      Fasting duodenal migrating myoelectric (or motor) complexes (MMCs) occurred at
      longer intervals in the short-term after 80% MSBR than in controls, and were
      simulated in long-term that in controls. MMCs arising from the duodenum were
      often migrated to the proximal jejunum, the jejunum above the anastomosis, and to
      the terminal ileum beyond the anastomosis. The velocity of duodenal MMC
      propagation was slowed in every intestinal segment in the short-term, and had not
      recovered even long after the operation. The duration of the postprandial period
      without duodenal MMCs was prolonged significantly in the short-term, and still
      remained longer in the long-term than in controls. These findings suggest that
      changes in gut motility after MSBR tend to compensate for the shorter intestine
      and maintain small bowel absorption early postoperatively, and adaptations of
      motility would occur over the long-term to increased intestinal absorption.

PMID- 8563056
TI  - Animal models and vaccine development.
AB  - Following the demonstration of Helicobacter pylori as a major gastroduodenal
      pathogen there was a need to develop animal models in order to investigate
      mechanisms of pathogenesis and to be able to test new treatment strategies.
      Helicobacter pylori will only colonize a limited number of hosts including non
      human primates, germ-free or barrier raised piglets, germ-free dogs and recently
      laboratory raised cats. Although these models have proved useful there is a need
      for more convenient small animal models. The ferret infected with its natural
      gastric organism, Helicobacter mustelae, is the only other animal to show peptic
      ulceration and has been successfully used to investigate gastritis and
      antimicrobial agents. The other commonly used animal model is the laboratory
      mouse or rat infected with either Helicobacter felis or Helicobacter heilmannii,
      bacteria that normally colonize cat or dog gastric mucosae. Active/chronic
      gastritis, gastric atrophy, and lymphoma-like lesions have been shown to develop
      in H. felis infected mice. The most recent and exciting use of an animal model
      has been the use of the H. felis mouse model in the development of human vaccines
      against H. pylori. Mice can be protected against infection with large doses of
      viable H. felis by oral immunization using sonicates of H. felis or H. pylori or
      recombinant H. pylori urease together with cholera toxin or cholera toxin-B
      subunit as the mucosal adjuvant. More importantly it has been shown that
      immunization of already infected animals results in eradication of infection.
      This raises the intriguing possibility that therapeutic immunization might be a
      viable option in the management of Helicobacter-associated disease. If
      immunization as a therapy of peptic ulcers was combined with short-term acid
      suppression, the possibility of reinfection may also be eliminated. In those
      countries where H. pylori infection rates are very high and infection occurs at
      an early age, large scale oral immunization of sections of the community would
      not only protect the young from the deleterious consequences of long-term H.
      pylori infection but could also cure existing disease.

PMID- 8563059
TI  - [Effects of low anterior resection on colonic motor activity and defecation. An
      experimental study].
AB  - The functional disorder of defecation after low anterior resection (LAR) was
      studied from the aspect of colonic motility in an experiment with dogs using a
      strain gage transducer, and the following results were obtained: 1) In early
      phase after LAR, the frequency of the colonic contractile waves increased at the
      proximal and distal sites of the anastomosis in both subgroups of dogs denervated
      and innervated of hypogastric and pelvic nerves. The increase was more remarkable
      at the distal site of the anastomosis. Also, the contractile waves were not
      propagated across the anastomosis. 2) After LAR, strong colonic contractions
      occurred during defecation only at the distal anastomosis. Various patterns of
      contraction time required for defecation were demonstrated as compared to a
      single pattern in control dogs. 3) The frequency of the occurrence of colonic
      contractile waves and the propagation of the contraction tended to be normalized
      with time after LAR both in denervated and innervated groups, though the recovery
      was faster in the latter subgroup. 4) The frequency of defecation increased after
      LAR both in denervated and innervated groups compared to be in the control dogs,
      though more remarkable in the denervated groups. Although tended to be gradually
      normalized with time after LAR, the colectomized dogs required a long time for
      normalization of the frequency of defecation. These results suggested the
      significant effect of reduction in reservoir space and disturbed continuity of
      intramural plexus caused by colectomy. Less severity, however, of functional
      disorder of defecation and earlier recovery from colonic motility disorder in the
      subgroup of the dogs innervated of autonomic nerves indicated usefulness of
      retaining autonomic nerves in colectomy.

PMID- 8563060
TI  - [Relation between electrogastrography and gastric electromyogram, mechanical
      activity].
AB  - Electrogastrography (EGG) appears to be useful method to evaluate the gastric
      motility as noninvasive approach. However, it is not known what EGG means. The
      aim of this study is to make clear the meanings of electrical activity recorded
      dy EGG for gastric motility. EGG recorded by cutaneous electrodes was compared to
      gastric electromyogram recorded by serosal electrodes and gastric mechanical
      activity recorded by straingauge transducer in anesthetized and conscious dogs.
      EGG recordings were preserved when gastric mechanical activity was not
      recognized. In digestive state, amplitude of EGG, electromyogram and mechanical
      activity increased significantly (p < 0.01). Significant correlation between
      amplitude of EGG and amplitude of electromyogram and mechanical activity of
      antrum were seen (p < 0.01). In interdigestive state, amplitude of EGG in phase 3
      increased significantly (p < 0.05) compared to that in phase 1. Significant
      correlation between amplitude of EGG and amplitude of electromyogram and
      mechanical activity were seen in phase 2 (p < 0.01). EGG reflected electrical
      control activity (ECA) and electrical response activity (ERA). EGG recordings
      showed electromyogram and mechanical activity of gastric antrum. Amplitude of EGG
      reflected electromyogram and mechanical activity in phase 2 in interdigestive
      state. EGG waves did not always agree on myoelectrical waves.

PMID- 8563058
TI  - [The control of smooth muscle tissues by nonadrenergic noncholinergic (NANC)
      nerve fibres in the autonomic nervous system].
AB  - Smooth muscle cells distributed in the visceral organs are under the control of
      the autonomic nervous system, and contraction or relaxation of the muscle cells
      plays an important physiological role in the control of blood pressure, motility
      of the digestive, respiratory and urinary tracts and secretion. Recent
      physiological, pharmacological and histochemical investigations indicate that
      neurotransmitters other than acetylcholine or noradrenaline are involved in
      peripheral autonomic neuro-effector transmission, and these neurotransmitters are
      generally termed non-adrenergic, non-cholinergic (NANC) neurotransmitters. The
      neurotransmitters responsible for excitatory and inhibitory NANC
      neurotransmission (e-NANC and i-NANC respectively) have not been conclusively
      identified, but ATP, nitric oxide (NO) and peptides such as VIP and substance P
      are candidates for these roles. In this review, we discuss the possible role of
      ATP and NO as e- or i-NANC neurotransmitter in the digestive, respiratory and
      urinary tracts. Much of the work on NANC innervation in the digestive tract has
      been carried out on the circular muscle layers of the ileum. This receives
      inhibitory NANC innervation with ATP responsible for fast relaxation and VIP, and
      possibly NO, for the slow response. Early and late excitatory junction potentials
      can be recorded in the presence of atropine. The second is due to substance P
      since it is blocked in the presence of spantide and by desensitization of the
      tissue with high doses of substance P. The transmitter responsible for the early
      NANC contraction has not been identified. Electrical field stimulation (EFS)
      applied to the tracheal smooth muscle during contraction induced by 5-HT in the
      presence of atropine and guanethidine elicited monophasic NANC relaxation. By
      contrast, NANC relaxation elicited in the smaller airways was biphasic,
      comprising an initial fast component followed by a second slow one. L-NAME
      selectively abolished the first component without affecting the second. VIP
      antagonists or alpha-chymotrypsin considerably attenuated the amplitude of the L
      NAME insensitive relaxation. These results indicate that at least two
      neurotransmitters, possibly NO or NO-containing compounds and VIP, are involved
      in i-NANC neurotransmission in the airway. In the urinary bladder a large,
      transient atropine resistant contraction occurs in response to pelvic nerve
      stimulation. This is blocked by alpha, beta methylene ATP suggesting that it is
      due to ATP. There is no evidence of inhibitory innervation. In the urethra
      contraction is completely blocked by atropine and guanethidine; a rapid NANC
      relaxation is abolished by drugs that block NO synthesis. Nerves containing
      peptides supply both urethra and bladder and may also be involved. These results
      suggest that all visceral smooth muscles may receive inhibitory NANC innervation
      involving NO. ATP produces contraction of the urinary bladder but relaxation of
      the digestive tract. The role of peptides is not yet clear but there is evidence
      that substance P may be an excitatory transmitter and VIP an inhibitory
      transmitter in many organs.

PMID- 8563061
TI  - Growth Hormone and Growth Factors in Endocrinology and Metabolism. Proceedings
      and abstracts of the 19th International Symposium. Prague, Czech Republic, 21-22
      April 1995.

PMID- 8563062
TI  - Volumetric bone mineral density--a potential role in paediatrics.
AB  - The use of areal bone mineral density (aBMD) in paediatric populations has
      aroused some concern, as it fails to take the age-related increase in bone
      thickness into account. We have developed a measure of true bone density,
      volumetric bone mineral density (vBMD), which is independent of age and height.
      In order to examine the relationship between growth parameters, aBMD and vBMD, we
      studied patients with phenylketonuria (PKU, n = 40), chronic renal failure (CRF,
      n = 27) and chronic asthma (n = 19). aBMD of the femoral neck and the mid-femoral
      shaft was measured using dual energy X-ray absorptiometry (DXA), vBMD was
      calculated on the basis of values of bone mineral content and bone dimension
      provided by DXA, with the assumption that both sites are cylinders. aBMD and vBMD
      were then compared with the normal reference, expressed as a standard deviation
      score (SDS). aBMD and vBMD were normal in the femoral neck region of the PKU
      group, but aBMD, either standardized for age or for height, was low in the
      femoral shaft region (p < 0.01). In the CRF group, profound growth retardation
      was seen (mean height SDS, -3.2) and aBMD and vBMD were both low in the femoral
      shaft region but not in the femoral neck. In the asthma group, aBMD for age was
      low at both sites, but vBMD did not differ from that seen in normal individuals.
      We conclude that the true vBMD provides a different interpretation of bone
      density compared with aBMD and requires further evaluation in paediatrics because
      of its age and height independence.

PMID- 8563063
TI  - Bone mass acquisition during infancy, childhood and adolescence.

PMID- 8563064
TI  - Genetic regulation of peak bone mass.

PMID- 8563065
TI  - Is the central nervous system a target for growth hormone and insulin-like growth
      factors?

PMID- 8563066
TI  - Late consequences of a low peak bone mass.

PMID- 8563067
TI  - Growth hormone/insulin-like growth factor I axis in children treated for brain
      tumours: relationship to chemotherapy and nutrition.

PMID- 8563068
TI  - Growth hormone deficiency in children treated for leukaemia.

PMID- 8563069
TI  - Growth, puberty and obesity after treatment for leukaemia.
AB  - Final height, body proportions, pubertal growth and body mass index were studied
      retrospectively in 142 survivors of acute lymphoblastic leukaemia (ALL).
      Treatment consisted of combination chemotherapy and cranial irradiation (18 or 24
      Gy). Significant standing height loss and disproportion, with a relatively short
      back, was seen in both radiation dose groups. Girls were more severely affected
      than boys. Pubertal growth was adversely affected, with a reduction in peak
      height velocity in both sexes. Puberty occurred early in girls but at the normal
      time in boys. Nearly half the group were obese at final height, with no
      significant difference in incidence between the sexes. The relative roles of
      cranial irradiation and chemotherapy in the disturbance of growth, puberty and
      body composition observed in survivors of childhood ALL remain unclear. The
      aetiology is almost certainly multifactorial, with radiation-induced growth
      hormone insufficiency, early puberty, steroids and chemotherapy all having a
      role.

PMID- 8563070
TI  - Effect of chemotherapy on growth.
AB  - Growth restriction has been demonstrated clearly following the treatment of
      childhood malignancies, even in the absence of irradiation to the hypothalamic
      pituitary axis. The use of CT and spinal irradiation in the original treatment of
      brain tumours has a marked effect on growth. This effect is most profound in
      children who have received both treatments and cannot be overcome using GH
      therapy at conventional doses.

PMID- 8563071
TI  - Growth and endocrine disturbances after bone marrow transplantation in childhood.

PMID- 8563072
TI  - Patient evaluation of a new injection pen for growth hormone treatment in
      children and adults.
AB  - The aim of this study was to evaluate patients' perception and acceptance of a
      new multi-dose injection device (Genotropin Pen) for recombinant growth hormone
      (GH) supplied in a two-chamber cartridge. The pen is combined with a very thin
      needle (B-D Microfine + (29 G) and meets future demands when dosing of GH will be
      changed from International Units (IU) to milligrams (mg). A total of 39 children
      receiving GH treatment (East Hospital, Gothenburg and St Bartholomew's Hospital,
      London), aged between 7 and 17 years, and 39 GH-treated adults (Sahlgrenska
      Hospital, Gothenburg and Karolinska Hospital, Stockholm), aged between 20 and 68
      years, participated in the study. The daily dose ranged from 0.3 mg to 2.6 mg.
      The injections were given subcutaneously, once daily, and most of the patients
      used the thigh as an injection site. After a trial period of 2 weeks, injection
      technique, pain, fear of injection and convenience of the Genotropin Pen were
      compared with the experience with the prestudy device (Genotropin KabiPen 16,
      16(8) or 36) by questionnaire. A total of 95% of the patients preferred the
      Genotropin Pen to the prestudy device for the following reasons: a greater
      certainty of correct dosing with the digital display; the possibility of
      correcting the set dose; the lock function of the injection button when injection
      is complete; more comfortable to hold due to the design and the plastic material;
      and reduced pain when injecting due to the thinner needles. Four patients (5%)
      preferred the prestudy device KabiPen as they considered this to be 'good
      enough'. Thus, the Genotropin Pen is a convenient injection device and most
      patients prefer it to the KabiPen.

PMID- 8563073
TI  - Short stature and psychosocial assessment.

PMID- 8563074
TI  - Genetics and molecular biology in short stature.

PMID- 8563075
TI  - Glucocorticoids and growth problems.

PMID- 8563076
TI  - Growth hormone insensitivity syndromes.

PMID- 8563077
TI  - Bone absorptiometry: a critical appraisal of various methods.

PMID- 8563078
TI  - Kidney-limited recurrence in a patient with microscopic polyarteritis.
AB  - A 58-year-old woman with kidney-limited recurrence of microscopic polyarteritis
      (MPA) is described. The patient had a history of histologically-confirmed MPA 7
      years previously, which had been in remission with corticosteroid treatment for
      30 months followed by no medication thereafter. However, in February 1994,
      clinical manifestations including leg edema and proteinuria developed, followed
      by rapidly progressive renal insufficiency. Renal biopsy revealed crescentic
      glomerulonephritis with necrotizing vasculitis. Furthermore, at the same time
      antimyeloperoxidase antibody (MPO-ANCA) was detected in plasma. She was diagnosed
      as having kidney-limited recurrence of MPA without systemic presentation.
      Corticosteroid therapy was reinstituted, and the renal function improved, with a
      decrease in the titer of MPO-ANCA.

PMID- 8563079
TI  - Hyperresponsiveness of granulocytes to anaphylatoxins, C5a and C3a, in Churg
      Strauss syndrome.
AB  - A 50-year-old man with Churg-Strauss syndrome showed granulocytes (GNLs) which
      generated more superoxide anion (O2-) than GNLs from healthy subjects following
      in vitro stimulation with C5a or C3a. Production of O2- subsided as the clinical
      symptoms improved with steroid treatment. A hyperresponsiveness of GNLs may be
      involved in this disorder.

PMID- 8563081
TI  - Recurrent Guillain-Barre syndrome in Japan.
AB  - The clinical profiles of 11 Japanese patients with recurrent episodes of Guillain
      Barre syndrome (GBS), including 3 of our cases out of a total of 76 patients (48
      males and 28 females), are reviewed. The recurrence rate was estimated as 4%.
      Among the 11 Japanese patients, 10 were male. Various viral infections had been
      confirmed in 1 case. No patients showed recurrent ophthalmoplegia. Sensory
      involvement varied from one episode to the next. These findings suggest the
      changing distribution of the demyelinating lesions and possibly a different
      reaction to the unknown pathogens in the recurrence of GBS.

PMID- 8563080
TI  - Longitudinal study of serum and cerebrospinal fluid (CSF) class-specific
      antibodies against Campylobacter jejuni and GM1 ganglioside in Guillain-Barre
      syndrome.
AB  - We report two Guillain-Barre Syndrome (GBS) patients with culture-proven
      Campylobacter jejuni (Penner19/Lior 7). Elevated anti-C.jejuni IgA antibody
      declined to the normal range within one month, elevation of anti-C.jejuni IgM
      antibody lasted for 3 months and the titers of anti-C.jejuni IgG antibody were
      still elevated at one year after the neurologic onset. Serological criteria for
      antecedent C.jejuni infection in GBS patients should require 1) high titer of
      serum IgA and/or IgM antibody against C.jejuni followed by seroconversion of the
      IgA and/or IgM and 2) a 4-fold decline of IgG serum dilution against C.jejuni.
      Anti-C.jejuni antibodies in cerebrospinal fluid (CSF) reached the maximum value
      at one month after their neurologic onset which may not be responsible for the
      main pathological mechanism in the development of GBS. Anti-GM1 antibodies in
      serum and CSF were parallel with those of anti-C.jejuni antibodies during the
      course of the disease.

PMID- 8563082
TI  - Pulmonary arteriovenous fistula associated with unequal branching of the
      pulmonary artery system.
AB  - A 60-year-old woman was admitted to our hospital with shortness of breath and was
      diagnosed to have pulmonary arteriovenous fistula with unequal branching of the
      pulmonary artery system, as assessed by pulmonary angiography. The concomitant
      occurrence has not been reported previously. Although the etiology of these
      abnormalities is unknown, these abnormalities are considered to have occurred
      during an early stage of fetal development. The analysis of a concomitant
      occurrence of these abnormalities may be useful in elucidating the etiology of
      pulmonary arteriovenous fistula.

PMID- 8563083
TI  - Oral low-dose etoposide therapy for refractory multiple myeloma with
      extramedullary involvement.
AB  - A 65-year-old man was hospitalized with IgG kappa-type multiple myeloma (MM) and
      enormous subcutaneous plasmacytomas. Two different combination chemotherapy
      regimens (MMCP and AVPP) and alpha-interferon therapy were ineffectual. Oral
      administration of etoposide at 50 mg/day was subsequently started, the tumors
      completely disappeared after 5 months. The blood level of monoclonal protein
      became undetectable after 8 months of continuous treatment. The side effect noted
      was loss of hair. The course in this patient suggests that long-term daily low
      dose administration of etoposide should be attempted in patients with refractory
      MM and extramedullary plasmacytoma.

PMID- 8563084
TI  - Dissociated motor loss syndrome with cavities in the anterior horns.
AB  - A 74-year-old man developed proximal muscular weakness and wasting of the left
      upper extremity without sensory disturbance or myelopathic symptoms. The muscle
      atrophy had not progressed for a few years. Radiological examination of the spine
      showed cervical disc herniation. These findings and electrophysiological studies
      excluded motor neuron diseases, permitting the diagnosis of dissociated motor
      loss syndrome. Interestingly, delayed computerized tomographic myelography
      disclosed cavities in the anterior horns of the spinal cord, which coincided with
      the clinical symptoms. Previous radiological and pathological examinations showed
      formation of such cavities within the spinal cord resulting from chronic
      compression, which was followed by ischemic change. In this context, the present
      case supports ischemia as a cause of dissociated motor loss syndrome.

PMID- 8563085
TI  - Pulmonary thromboembolic hypertension in systemic lupus erythematosus with lupus
      anticoagulant: histopathological analysis of localization and distribution of
      thromboemboli in pulmonary vasculature.
AB  - We report a systemic lupus erythematosus patient with lupus anticoagulant
      accompanied by pulmonary thromboembolic hypertension possibly due to large
      vegetation of the tricuspid valve of the heart. Histopathological analysis of
      localization and distribution of thromboemboli in pulmonary vasculature revealed
      that the organized thromboembolic occlusion of multiple blood vessels (99 out of
      222 arteries), might be responsible for the pulmonary hypertension both in
      quality and quantity. The contribution of lupus anticoagulant to the pathogenesis
      of Libman-Sacks endocarditis in systemic lupus erythematosus, and its possible
      relationship to pulmonary thromboembolic hypertension are discussed.

PMID- 8563086
TI  - CD34-positive blastoma in a patient with idiopathic myelofibrosis.
AB  - We report CD34-positive "blastoma" which developed in a patient with idiopathic
      myelofibrosis (IMF). A 48-year-old woman was diagnosed as having essential
      thrombocythemia, then the disease had transformed into IMF 41 months later.
      Finally, a subcutaneous tumor, composed of blastic cells positive for CD34 but
      negative for lineage-specific antigens, developed without any evidence of
      systemic leukemia transformation.

PMID- 8563087
TI  - Eight cases of gastric tumors with calcification.
AB  - Gastric tumors with calcification have been considered to be relatively rare. We
      treated 8 cases of tumors involving calcification, 4 cases of gastric carcinomas
      and 4 other cases of submucosal tumors with ulceration. These cases are reported
      along with a review of the cases reported in Japan.

PMID- 8563088
TI  - Mitochondrial DNA mutations in diabetes mellitus and heart disease.

PMID- 8563089
TI  - New diagnostic techniques for the detection of opportunistic pathogens involved
      in pneumonia in immunocompromised hosts.

PMID- 8563090
TI  - More acquired immunodeficiency syndrome (AIDS) dementia complex in Japan?

PMID- 8563091
TI  - Renal vasculitis and antineutrophil cytoplasmic antibody.

PMID- 8563092
TI  - Pulmonary hypertension and the antiphospholipid syndrome.

PMID- 8563093
TI  - Endothelium-dependent regulation of the cardiovascular system.
AB  - Vascular endothelial cells play an important role in modulating cardiovascular
      function, by liberating several vasoactive substances, such as prostacyclin,
      endothelium-derived relaxing factor/nitric oxide, a hyperpolarizing substance,
      and vasoconstrictor substances. Their roles in the cardiovascular system include
      modulation of the contraction of the underlying vascular smooth muscle,
      interaction between blood components and blood vessel wall, vascular growth, as
      well as regulation of the cardiovascular system at several levels beyond the
      vascular wall. Alterations in the endothelial functions and the related processes
      are now known to be involved in the pathogenesis of many cardiovascular diseases,
      including hypertension and atherosclerosis. Thus, the impaired endothelial
      regulation of the cardiovascular system may have an important implication for the
      development and progression of many cardiovascular diseases.

PMID- 8563094
TI  - Adult T-cell leukemia.
AB  - Adult T-cell leukemia (ATL) was first reported in Japan, where it has a high
      incidence in the southwestern region. The retrovirus, human T-lymphotropic virus
      type I (HTLV-I), is the causative agent of ATL. In ATL-endemic areas, the rate of
      HTLV-I carriers is high. A definite diagnosis of ATL is based on the presence of
      HTLV-I proviral DNA in the tumor cell DNA. ATL cells originate from the CD4
      subset of peripheral T cells. ATL shows diverse clinical features but can be
      divided into four subtypes:acute, chronic, smoldering, and lymphoma type.
      Chemotherapy is not effective; the acute and lymphoma types have a poor
      prognosis. Familial occurrence of ATL is common. HTLV-I infection is caused by
      transmission of live infected lymphocytes from mother to child, from man to
      woman, or by blood transfusion. Infection with HTLV-I can lead to other diseases,
      including HTLV-I-associated myelopathy/tropical spastic paraparesis and HTLV-I
      uveitis.

PMID- 8563095
TI  - Hypertrophic cardiomyopathy in patients with diabetes mellitus associated with
      mitochondrial tRNA(Leu)(UUR) gene mutation.
AB  - Left ventricular function and morphology were assessed using M-mode
      echocardiography in 3 patients with diabetes mellitus associated with
      mitochondrial tRNA(Leu)(UUR) gene mutation, who were free of clinical,
      electrocardiographic, or thallium scan evidence of ischemic heart disease.
      Echocardiograms revealed hypertrophic cardiomyopathy in all 3 patients.
      Hypertrophy of the interventricular septum was mild in Cases 1 and 3 (12 and 13
      mm, respectively) and severe in Case 2 (22 mm) (normal 7-10 mm). When they had
      neither signs nor symptoms suggestive of congestive heart failure, percentage
      fractional shortening (%FS), an index of wall motion of the left ventricle
      (normal > 28%), was normal in Cases 2 and 3 (28 and 32%, respectively) whereas it
      was slightly decreased in Case 1 (22%). In Case 1 with mild hypertrophy, the
      development of congestive heart failure was associated with a marked decrease in
      %FS to 13%; this patient responded well to diuretics and captopril and %FS rose
      to 22%. However, a mild decrease in %FS to 21% caused congestive heart failure in
      Case 2 with severe hypertrophy. His response to treatment was marginal. The
      present study indicates that mitochondrial DNA analysis should be done in
      patients with diabetic cardiomyopathy, and that sequential echocardiography is
      invaluable for the detection of hypertrophic cardiomyopathy and the management of
      subsequent myocardial dysfunction in patients with mitochondrial diabetes
      mellitus and cardiomyopathy.

PMID- 8563096
TI  - Varied effects of thoracic irradiation on peripheral lymphocyte subsets in lung
      cancer patients.
AB  - To investigate the influence of thoracic irradiation on immunological competence
      in patients with lung cancer, we examined the changes in peripheral blood
      lymphocyte subsets in 15 patients before and after radiation therapy by two-color
      flow cytometry techniques. After radiation therapy, the percentage and the
      absolute number of CD4+CD45RA+ cells (naive T cells) and CD56+ and/or CD16+ cells
      (NK cells) decreased. The percentage of CD4+human leukocyte antigen-DR(HLA-DR)+
      cells (activated CD4T cells) and CD8+HLA-DR+ cells (activated CD8T cells)
      increased, although the absolute number did not change significantly. Naive T
      cells may be more selectively damaged than memory T cells by thoracic
      irradiation, through their recirculation behavior. The reduction of natural
      killer (NK) cells is disadvantageous for anti-tumor immunity. The percentage of
      HLA-DR positive T lymphocytes was significantly increased, and thus the
      possibility of HLA-DR enhancement by irradiation cannot be excluded. Therefore,
      thoracic irradiation has numerous varied effects on the immunological system of
      lung cancer patients.

PMID- 8563097
TI  - Smoking promotes insidious and chronic farmer's lung disease, and deteriorates
      the clinical outcome.
AB  - Although the prevalence of serum precipitating antibodies for farmer's lung
      disease (FLD) is lower in smokers than in nonsmokers and FLD predominates in
      nonsmokers, the affects of smoking on the clinical course of the disease is not
      known. We compared the clinical findings and the prognosis between 12 smokers (SM
      FLD) and 31 non-smokers with FLD (NS-FLD). There was no difference in age, sex,
      working years on farm, clinical symptoms, laboratory findings, radiographic
      findings, between the two groups. However, for the type of onset on the first
      visit for FLD, "acute single episode" type was less common, and "recurrent" and
      "insidious onset" types were more common in SM-FLD than in NS-FLD (8.3 vs 58.1,
      91.7 vs 41.9%, respectively, p < 0.05). Although working status and mask wearing
      status were not significantly different between the two groups after the
      diagnosis of FLD, patients with symptoms and/or radiographic abnormalities of FLD
      of more than 6 months were found more frequently in SM-FLD than in NS-FLD (66.7
      vs 19.4%, p < 0.005). And also SM-FLD had more recurrences of FLD than NS-FLD
      after the initial diagnosis of FLD (1.58 +/- 1.56 vs 0.47 +/- 1.07, p < 0.05). SM
      FLD tended to have lower % VC than NS-FLD (73.6 +/- 7.4 vs 88.5 +/- 3.9%,
      respectively, p = 0.06). Regarding the prognosis, the 10-year survival rates were
      70.7% in SM-FLD, and 91.5% in NS-FLD (p < 0.05). These results suggest that
      smoking may make FLD insidious and chronic, and deteriorates the clinical
      outcome.

PMID- 8563098
TI  - Autonomic nervous disorder in motor neuron disease: a study of advanced stage
      patients.
AB  - Autonomic functions were studied in 10 respiratory-support patients with motor
      neuron disease (MND) at its most advanced stage by means of hemodynamic function
      tests. The mean duration of disease was 83.4 months (SD 28.0, range 50-140
      months). All the patients in this study had lost their ability to breathe
      spontaneously and were ventilated by respirator. Hemodynamic function tests were
      performed in 8 out of 10 patients. These patients showed exaggerated sympathetic
      vasomotor reflexes, increased reflex hypertension and tachycardia in response to
      the cold pressor test and increased response to administration of adrenaline.
      However, the responses to both the Aschner eyeball pressure test and injection of
      atropine were normal, indicating normal parasympathetic nervous system function.
      Plasma and urine levels of norepinephrine, epinephrine and their metabolites were
      almost normal in all 10 patients, as were serum dopamine-beta-hydroxylase levels.
      In patients with the most advanced stage of MND, hyperfunction of the adrenergic
      sympathetic nervous system was observed, and this was considered to be a symptom
      characteristic of MND.

PMID- 8563099
TI  - Detection of Pneumocystis carinii, Mycobacterium tuberculosis, and
      cytomegalovirus in human immunodeficiency virus (HIV)-infected patients with
      hemophilia by polymerase chain reaction of induced sputum samples.
AB  - The purpose of this study was to diagnose the initial stage of acute pulmonary
      infections due to Pneumocystis carinii (P. carinii), Mycobacterium tuberculosis
      (M. tuberculosis), and cytomegalovirus (CMV) by polymerase chain reaction (PCR)
      combined with the induced sputum method in hemophilia patients infected with
      human immunodeficiency virus (HIV). Induced sputum and PCR were obtained at each
      outpatient visit or when any respiratory symptoms were present during a one-year
      period. All patients with a CD4+ count of less than 200 x 10(6)/l were given
      prophylactics against P. carinii pneumonia (PCP). PCR was conducted 111 times in
      29 patients. M. tuberculosis DNA was detected in 1 patient and CMV DNA in 4
      patients. P. carinii DNA was not detected. PCR on induced sputum samples is
      sensitive for the rapid detection of the initial stage of respiratory events. PCP
      prophylaxis changes the clinical manifestations of HIV infection.

PMID- 8563100
TI  - Transition of morphologic features in lupus nephritis: does steroid therapy
      accelerate glomerulosclerosis?
AB  - We retrospectively evaluated the morphologic change of 28 follow up biopsies from
      24 cases of lupus nephritis according to the classification of the World Health
      Organization and determined the activity index (AI) and the chronicity index
      (CI). In the cases with biopsies repeated within 6 months, the AI decreased
      significantly from 6.7 +/- 1.3 to 3.5 +/- 0.8, while the CI showed no significant
      change. In cases which were rebiopsied after longer intervals, AI increased
      significantly from 3.2 +/- 0.7 to 7.5 +/- 1.2; the CI did not change
      significantly. When AI and CI changes in the cases biopsied again beyond 6 months
      were compared with respect to therapy, AI showed no significant difference in the
      methylprednisolone pulse therapy group but was significantly increased in the
      oral steroid therapy group. The CI tended to be increased in both groups, but not
      significantly. Steroid pulse therapy was effective in improving active lesions
      with a high AI. Steroid therapy for lupus nephritis prevented short-term
      progression of glomerulosclerosis and did not accelerate glomerulosclerosis.

PMID- 8563101
TI  - Primary hyperparathyroidism associated with multiple myeloma.
AB  - A 73-year-old woman was diagnosed as primary hyperparathyroidism. Hypercalcemia
      recurred after parathyroidectomy, though serum calcium concentration temporarily
      resumed to normal. Hypercalcemia was eventually shown to be due to multiple
      myeloma. In spite of the frequent association of hypercalcemia with malignant
      disease and the relative frequency of primary hyperparathyroidism as a cause of
      hypercalcemia, primary hyperparathyroidism accompanied by multiple myeloma has
      been considered in only a limited number of reports. Here, the cases in the
      literature are reviewed and discussed.

PMID- 8563102
TI  - Spontaneous resolution of an acute spontaneous spinal epidural hematoma without
      neurological deficits.
AB  - A 46-year-old woman presented with sudden severe pain in the interscapular
      region. Physical examination, including detailed neurological evaluation, did not
      disclose any abnormalities. However, magnetic resonance imaging revealed an
      epidural hematoma anterior to the thoracic spinal cord and its spontaneous
      resolution thirty days after onset. Her hospital course was uneventful. To our
      knowledge, this report documents the first case of a spontaneous spinal spidural
      hematoma without neurological deficits. Spinal epidural hematoma may be more
      common than previously thought because some cases have probably been misdiagnosed
      as transient back pain of unknown etiology.

PMID- 8563103
TI  - A hemophiliac with human immunodeficiency virus (HIV)-1-associated dementia
      complex.
AB  - We report a 29-year-old male hemophiliac with human immunodeficiency virus (HIV)
      1-associated dementia complex, who died 2.5 months after the onset of dementia.
      The patient's cognitive abnormalities including forgetfulness, loss of
      concentration and slowing of thought appeared about 7 years after HIV infection.
      His neurological symptoms were characterized as progressive dementia, episodic
      consciousness loss, transverse myelopathy and peripheral neuropathy. He had
      generalized slow waves in electroencephalogram (EEG), progressive cerebral
      atrophy and a diffuse high intensity lesion in the white matter as shown by T2
      weighted brain magnetic resonance imaging (MRI). We emphasize the significance of
      neurological complications, especially acute progressive dementia, in Japanese
      patients with acquired immunodeficiency syndrome (AIDS).

PMID- 8563104
TI  - Preservation of the ventricular gradient.

PMID- 8563105
TI  - Anticipation of age-of-onset in familial amyloidotic polyneuropathy and its
      pathogenesis.

PMID- 8563106
TI  - Clinical manifestations and prognosis of Wegener's granulomatosis.

PMID- 8563107
TI  - Summer-type hypersensitivity pneumonitis.
AB  - Summer-type hypersensitivity pneumonitis (SHP), the most prevalent type of HP in
      Japan, is caused by seasonal mold contamination in the home environment. The
      causative agent of the disease is Trichosporon cutaneum. The fungus grows in
      warm, moldy, decaying organic matter, and scatters in the air from the colonizing
      places. The inhaled fungi sensitize susceptible patients intratracheally and
      induce the disease. Glucuronoxylomannan of the fungus has a potent antigenicity
      that causes granulomatous alveolitis. Assay of anti-T. cutaneum antibody is very
      useful to establish the diagnosis of the disease because the antibody activity is
      virtually positive in all cases of the disease. Elimination of T. cutaneum from
      the colonizing places prevents recrudescence. SHP, a new form of HP, had been
      considered to be peculiar to Japan, but the first case of SHP outside Japan was
      identified in Korea last year. Soon it will be recognized in many countries of
      temperate and tropical clime.

PMID- 8563108
TI  - Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP): recent perspectives.
AB  - Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) is a well-defined clinicopathological entity, and
      approximately 1,900 patients with HAM/TSP have been reported in the world.
      Improved polymerase chain reaction (PCR)-based in situ techniques have allowed a
      better appreciation of the cellular localization of the virus activation in
      infected patients, and there is accumulating evidence that HAM/TSP is
      characterized by a distributional bias of viral activation between the blood flow
      and central nervous system (CNS). This review summarizes the current status of
      our understanding of HAM/TSP, and emphasizes the possible pathogenic involvement
      of cellular interactions between infected cells and responding immunocompetent
      cells in the CNS of patients with HAM/TSP. In addition, the notable systemic
      manifestations with or without myelopathy in HTLV-I-infected individuals are
      described.

PMID- 8563109
TI  - Evidence for an increased intracellular free calcium concentration in platelets
      of bronchial asthma patients.
AB  - The pathogenesis of bronchial asthma is not yet fully understood. Recently much
      attention has been given to the hypothesis that intracellular free calcium
      ([Ca2+]i) metabolism is abnormal in various diseases. In this study we
      investigated whether [Ca2+]i exists abnormally in subjects with bronchial asthma.
      The [Ca2+]i in 32 treated or untreated subjects with bronchial asthma were
      compared with 63 normal subjects. Resting levels of [Ca2+]i were estimated by
      loading the fluorescent indicator Fura-2 in washed platelets. The [Ca2+]i level
      in the control subjects was 129.7 +/- 18.0 nM (mean +/- SD). However, in that of
      the bronchial asthma patients was 152.7 +/- 44.1 nM, significantly higher than
      that of the control subjects (p < 0.05). It is well recognized that an increase
      of [Ca2+]i in vascular smooth muscle involves contraction. The findings suggest
      that the same phenomenon is quite possible in the tracheal smooth muscle and that
      it plays an important role in the pathogenesis of bronchial asthma.

PMID- 8563110
TI  - Plasma adrenomedullin in various diseases and exercise-induced change in
      adrenomedullin in healthy subjects.
AB  - Adrenomedullin is a novel hypotensive peptide recently discovered in human
      pheochromocytoma. In the present study, we measured the plasma immunoreactive
      adrenomedullin of healthy subjects and patients with various diseases.
      Immunoreactive adrenomedullin was found to circulate in blood of the healthy
      subjects at a considerable concentration (3.3 +/- 0.3 fmol/ml). Plasma
      adrenomedullin was significantly increased in the patients with congestive heart
      failure (5.4 +/- 0.3 fmol/ml), essential hypertension (5.3 +/- 0.4 fmol/ml) and
      renal disease (4.9 +/- 0.4 fmol/ml). In healthy volunteers physical exercise
      significantly increased the plasma adrenomedullin concentration. The increase of
      adrenomedullin was inversely related to systolic blood pressure. These findings
      indicate that adrenomedullin participates in the circulation control in both
      physiological and diseased conditions. Although the exact origin of circulating
      adrenomedullin is still unknown, it is thought to be released rapidly by acute
      exercise, thereby regulating the cardiovascular system by its vasodilating
      activity.

PMID- 8563111
TI  - Cyclic guanosine monophosphate (cGMP), nitrite and nitrate in the cerebrospinal
      fluid in meningitis, multiple sclerosis and Guillain-Barre syndrome.
AB  - Recent evidence suggests the involvement of nitric oxide (NO) in inflammation and
      demyelination in the brain. To test this hypothesis, we measured NO markers in
      the cerebrospinal fluid from patients with bacterial meningitis (BM), aseptic
      meningitis (AM), multiple sclerosis (MS), and Guillain-Barre syndrome (GBS).
      Subjects with non-inflammatory neurologic diseases served as the controls. NO
      markers were cyclic guanosine monophosphate (cGMP) measured with an enzyme
      immunoassay, and nitrite and nitrate measured with the Griess reaction. Except
      for BM, cGMP was not increased in AM, MS or GBS compared with the controls.
      Nitrite and nitrate were unaltered in any of the groups studied. These results do
      not support the hypothesis that NO is increased in the brain in meningitis, MS or
      GBS. Otherwise cGMP, nitrite and nitrate in the cerebrospinal fluid do not
      reflect the increase in NO in the brain.

PMID- 8563112
TI  - Spatial ventricular gradient in patients with Wolff-Parkinson-White syndrome in
      comparison with normal subjects: vectorcardiographic evidence for significant
      repolarization changes due to preexcitation.
AB  - We investigated the use of the spatial ventricular gradient (VG) from
      vectorcardiogram (VCG) to determine whether significant repolarization
      differences were present in patients with WPW syndrome compared with normal
      subjects and also examined which VG parameter (i.e., elevation, azimuth, and
      magnitude) reflected the differences in repolarization properties during
      preexcitation. VG was calculated in 49 patients of Wolff-Parkinson-White (WPW)
      syndrome (group A: left-sided accessory pathway, n = 29; group B: right-sided, n
      = 20). Group N consisted of 607 normal subjects. In group A, the azimuth of VG
      was significantly (p < 0.01) greater than in groups B and N. In group B, the
      elevation of VG was significantly (p < 0.01) greater than in groups A and N.
      There were no significant differences in the magnitude of VG among groups. QRS
      duration was significantly (p < 0.01) related with the elevation of VG in group
      B. These findings suggested that VG is useful for spatial evaluation of
      repolarization abnormalities during preexcitation, which are related to the site
      of the accessory pathway.

PMID- 8563113
TI  - Neurologic features of chronic Minamata disease (organic mercury poisoning)
      certified at autopsy.
AB  - To better understand the neurologic events related to chronic Minamata disease
      (organic mercury poisoning), we studied data from 77 patients with Minamata
      disease as certified at autopsies performed from 1976 to 1994 (mean age: 72.3
      years). Major neurologic findings included: sensory impairment in 80.5% of the
      patients which was limited to the extremities in 42.9%. Impairment of lower
      extremity coordination was present in 35.8% of the patients, constriction of the
      visual fields in 28.8%, and retrocochlear hearing loss in 15.3%. There was no
      correlation between the degree of cerebellar incoordination and the methylmercury
      concentration in the cerebellum. Compared with the classic type of Minamata
      disease, the incidence of major neurologic findings was markedly decreased. In
      light of these findings, supplemental examinations including brain computed
      tomography (CT), magnetic resonance imaging (MRI), short latency somatosensory
      evoked potential (SSEP), or tremogram may be necessary to clinically diagnose
      Minamata disease, especially in atypical or mild cases.

PMID- 8563114
TI  - Change in the age of onset in patients with familial amyloidotic polyneuropathy
      type I.
AB  - To investigate the influence of environmental factor(s) on the pathogenesis of
      familial amyloidotic polyneuropathy (FAP) type I, the age of onset in 33 FAP
      patients in the Arao district of Kumamoto Prefecture in Japan and in 20 of their
      ancestors to the 3rd prior generation was carefully examined. The age of onset in
      FAP patients progressively became younger. This tendency was more apparent in
      female FAP patients than in male patients. Since the pathogenesis of amyloid
      formation in FAP as well as other amyloidosis diseases is not still elucidated,
      this phenomenon may be of interest.

PMID- 8563115
TI  - Acute graft-versus-host disease of the gut.
AB  - A 28-year-old man with acute promyelocytic leukemia at first early relapse
      received HLA-matched allogenic bone marrow transplantation (BMT) at first early
      relapse. Cyclosporin A and methotrexate were administered at conventional doses
      as a prophylaxis for graft-versus-host disease (GVHD). He presented with severe
      bloody diarrhea on day 87 after BMT. Examination of the lower gastrointestinal
      tract revealed diffuse mucosal change of inflammation. A diagnosis of late onset
      of acute gut GVHD was made, in the absence of other manifestations such as skin
      and liver involvement. A further survey is needed to clarify the incidence and
      the pathogenesis of atypical gut GVHD.

PMID- 8563116
TI  - Asterixis and astatic seizures in association with bilateral insular lesions in a
      patient with viral encephalitis.
AB  - We report a 48-year-old man who suffered from viral encephalitis and developed
      involuntary movements of the hands and astatic seizures as sequelae. T2-weighted
      magnetic resonance imaging of the brain showed high intensity areas in the
      bilateral insulae. Electroencephalography (EEG) revealed spike and slow wave
      complexes and high-amplitude slow waves. The involuntary movements of the hands
      were diagnosed as asterixis by electromyography. Asterixis affected both hands.
      Administration of sodium valproate aggravated asterixis and EEG findings, but
      treatment with clonazepam markedly improved these findings and astatic seizures.
      The present case indicates that insular lesions might be also responsible for the
      development of asterixis.

PMID- 8563117
TI  - Dilated cardiomyopathy associated with hyperthyroidism.
AB  - We report a case of dilated cardiomyopathy with hyperthyroidism. A 28-year-old
      man was admitted because of congestive heart failure and atrial fibrillation, and
      was newly diagnosed as having hyperthyroidism. Despite administration of
      antithyroid medication, he developed recurrent congestive heart failure. An
      echocardiogram revealed a moderately dilated left ventricle with diffuse
      hypokinesis. Though his thyroid function normalized, the patient's cardiac
      dysfunction did not improve. Beta-blocker therapy was begun with subsequent
      improvement in clinical symptoms. This suggests that beta-blocker treatment may
      be effective in patients with atrial fibrillation associated with cardiomyopathy
      and hyperthyroidism.

PMID- 8563118
TI  - Relapsing polychondritis associated with subclinical Sjogren's syndrome and
      phlegmon of the neck.
AB  - A 25-year-old woman, diagnosed with Sjogren's syndrome at age 20, presented with
      painful edema of her left neck. Three days later, she additionally complained of
      bilateral auricular pain, and her nasal cartilage was tender to palpation. She
      was diagnosed as having phlegmon on the basis of her neck findings. Anti-human
      cartilage antibodies were demonstrated by indirect immunofluorescence, and the
      diagnosis of relapsing polychondritis was established. The patient was
      administered antibiotics and a non-steroidal anti-inflammatory drug, and her
      symptoms gradually improved. Relapsing polychondritis is one of the possible
      complications of autoimmune diseases, and infection might be a precipitating
      factor for this disease.

PMID- 8563119
TI  - Chronic bronchobronchiolitis obliterans associated with Stevens-Johnson syndrome.
AB  - We report a case of bronchobronchiolitis obliterans associated with Stevens
      Johnson syndrome diagnosed using bronchography and bronchoscopy in a 25-year-old
      man with dyspnea. Eighteen months prior to admission, the diagnosis of Stevens
      Johnson syndrome due to anticonvulsant therapy was made at another hospital. On
      admission, the patient was wheezing and had overinflation of the lungs, with
      marked obstructive pulmonary dysfunction. Ventilation and perfusion scintigrams
      revealed multiple ventilation and perfusion defects but not mismatch.
      Bronchography revealed central bronchiectasis and obstruction of the peripheral
      bronchi. Occlusion of the fifth right basal bronchus was observed with fiberoptic
      bronchoscopy. Bronchography and bronchoscopy provide useful information for the
      diagnosis of this disease.

PMID- 8563120
TI  - Idiopathic colonic phlebitis with massive ascites.
AB  - We describe a 35-year-old woman with colonic phlebitis of unknown origin
      accompanied by effusion of serum protein into the peritoneal cavity. Abdominal
      ultrasonography and computed tomography showed massive ascites and edematous wall
      thickness of the colon. Laboratory examination of the peritoneal fluid showed a
      high concentration of protein, probably due to nonselective efflux of serum
      protein. The main histopathological finding was extensive edema of the submucosa
      with vasculitis in the colon. This kind of phlebitis with massive ascites, but
      without systemic involvement, and with the ascitic fluid almost identical to the
      serum protein level, has not been reported previously.

PMID- 8563121
TI  - Perforin-positive leukemic cell infiltration in the heart of a patient with T
      cell prolymphocytic leukemia.
AB  - Here we report a rare case of T-cell prolymphocytic leukemia in whom leukemic
      killer cells, expressing a cytolytic factor perforin, infiltrated the heart.
      Perforin may have directly injured myocardial cells which showed marked
      expression of human leukocyte antigens (HLAs) and intercellular adhesion molecule
      1 (ICAM-1) as well as costimulatory molecules B7 and B70, which are ligands for
      CD28 expressed on T-cells. In spite of chemotherapy against leukemic cells, this
      autoimmune process finally caused fatal congestive heart failure.

PMID- 8563122
TI  - Rhabdomyolysis associated with bacteremia due to Streptococcus viridans.
AB  - A 25-year-old man was admitted with complaints of fever and macrohematuria.
      Laboratory tests showed a substantial increase in serum creatine phosphokinase
      and creatinine in association with myoglobinuria and proteinuria. Blood culture
      grew Streptococcus salivarius and Streptococcus oralis. Findings of renal biopsy
      were compatible with IgA nephropathy. The glomeruli had a mild mesangial
      proliferation without crescentic lesions. Changes of the interstitium and tubules
      were not evident. The clinical course and laboratory results strongly suggested a
      possible link between Streptococcus salivarius/oralis infection, and
      rhabdomyolysis. Rhabdomyolysis is rarely seen as a complication of bacterial
      infection, and the present case emphasizes the importance of suspecting
      bacteremia due to Streptococcus salivarius/oralis in the presence of
      rhabdomyolysis.

PMID- 8563123
TI  - Wegener's granulomatosis complicated by arterial aneurysm.
AB  - Wegener's granulomatosis is a distinct clinicopathologic entity characterized by
      granulomatous vasculitis of the upper and lower respiratory tract and kidneys. A
      56-year-old Japanese man with Wegener's granulomatosis died of intraperitoneal
      hemorrhage from a ruptured aneurysm of his left gastric artery. Histological
      findings revealed necrotizing granulomatous vasculitis involving this artery. No
      previously published reports have described Wegener's granulomatosis patients
      with aneurysms in such a large artery. We conclude that this case represents
      either an atypical form of Wegener's granulomatosis or a polyangiitis overlap
      syndrome of Wegener's granulomatosis and classic polyarteritis nodosa.

PMID- 8563124
TI  - Warfarin-induced eosinophilic pleurisy.
AB  - A 51-year-old man was admitted to our hospital because of dry cough and low grade
      fever with right-sided pleural fluid and blood eosinophilia. Warfarin had been
      prescribed following coronary artery bypass grafting. After the discontinuation
      of warfarin the clinical and chest X-ray findings improved; readministration of
      the drug caused recurrent blood eosinophilia and pleural effusion in the other
      lung. Since no other specific etiologies for eosinophilia and pleural effusion
      were determined by extensive evaluation, warfarin seemed to be associated with
      his illness. This is the first report of warfarin-induced eosinophilic pleurisy.

PMID- 8563125
TI  - Arteriovenous malformation of the bronchial artery showing endobronchial
      protrusion.
AB  - The bronchoscopic findings of arteriovenous malformation of the bronchial artery
      are compared with findings on angiography and pathology. A non-pulsatile
      protrusion with engorged vessels on its glossy and uneven surface was seen at the
      distal portion of the right anterior segmental bronchus. A bronchial angiogram
      demonstrated that the protrusion corresponded to the hypervascular area of
      convoluted vessels. Histologically, a glossy, uneven surface and engorged vessels
      represented normal mucosa overlaying an extramuscular tortuous artery and
      proliferation of submucosal tiny vessels, respectively. These bronchoscopic
      findings were important clues for diagnosis.

PMID- 8563126
TI  - Cortical auditory disorder caused by bilateral temporal infarctions.
AB  - We present a 55-year-old man who suddenly became afflicted with a bilateral
      auditory disturbance. Auditory acuity was preserved relatively well. Brainstem
      auditory evoked potentials (BAEPs) were normal. Middle latency auditory evoked
      potentials (MLAEPs) revealed the total absence of all waves. Brain computed
      tomography (CT) showed infarctions of the temporal lobes bilaterally, involving
      the superior temporal and transverse temporal gyri. The recognition of verbal and
      nonverbal sounds was also impaired. Brain CT, MLAEPs and auditory recognition
      tests were useful in diagnosing the cortical auditory disorder.

PMID- 8563127
TI  - Hypertrophic cranial pachymeningitis with spinal epidural granulomatous lesion.
AB  - A 67-year-old woman with a one-year history of tinnitus and headache had multiple
      cranial nerve palsies of V, VII, VIII, IX, X, XI and spastic paraparesis. She
      also had a secretory otitis media. Gd-DTPA-enhanced magnetic resonance imaging
      (MRI) revealed hypertrophy of the dura of the posterior fossa and spinal epidural
      mass which extended from C7 to T10. A biopsy of the epidural mass showed chronic
      granulomatous change. These lesions were completely cured with administration of
      antibiotics. We believe this case of double-lesion of hypertrophic cranial
      pachymeningitis and spinal epidural granulomatous lesion originated from a
      bacterial infection secondary to the secretory otitis media.

PMID- 8563128
TI  - Sjogren's syndrome with pleural effusion.
AB  - Sjogren's syndrome (Sjs) can cause many organic changes, but is rarely
      accompanied by pleuritis. We report here a 62-year-old patient with subclinical
      Sjs who developed unilateral pleuritis with moderate effusion. He was diagnosed
      to have subclinical Sjs based on the positivity of anti SS-A/SS-B antibodies and
      the biopsy findings of minor salivary glands which revealed lymphocyte
      infiltration around the duct. In the pleural effusion, both increased lymphocytes
      and anti SS-A/SS-B antibodies were observed. He showed no signs of infection nor
      malignancy. There was no direct evidence that he had other collagen diseases
      which cause pleuritis. We conclude that the pleuritis was caused by Sjs. In
      patients with Sjs, activated polyclonal B lymphocytes and autoantibodies are
      considered to cause systemic tissue damage. This case indicates that these
      factors can cause pleuritis in Sjs patients.

PMID- 8563129
TI  - Adult T cell leukemia clinically manifested with ascites and pleural effusion.
AB  - A 62-year-old man with adult T cell leukemia (ATL) presented with complaints of
      anorexia and abdominal fullness. Evaluation revealed ascites and pleural
      effusion, but no lymph node swelling, hepatosplenomegaly, or skin involvement.
      The diagnosis of ATL was made by the detection of specific surface markers for T
      lymphocytes in pleural effusion and ascitic fluid, and by determination of human
      T cell leukemia virus type I (HTLV-I) proviral DNA integration in mononuclear
      cells of pleural effusion. This case was considered a rare type of ATL with
      infiltration of the pleura and peritoneum.

PMID- 8563130
TI  - Glycobiology of the cell surface: the emergence of sugars as an important feature
      of the cell periphery.

PMID- 8563131
TI  - Regarding the glycoprotein hormones and their sulphated oligosaccharides.

PMID- 8563132
TI  - Molecular cloning of eukaryotic glycoprotein and glycolipid glycosyltransferases:
      a survey.
AB  - The rapidity with which molecular sequence data are gathered continues to grow.
      The result is that, for many workers, it is increasingly difficult to keep
      abreast of the current state of play of molecular cloning, even for those genes
      that encode proteins of special interest. The clear success of the various
      worldwide genome projects has made this even more apparent, and by the end of
      1996 the complete determination of the nucleotide sequences of the genomes of two
      eukaryotes, Saccharomyces cerevisiae and Caenorhabditis elegans, will have either
      been completed or will be nearing completion. This article is an attempt to
      provide, in an easily accessible format, a compilation of genes and cDNAs that
      have been sequenced and deposited in GenBank that encode transferase enzymes
      involved in eukaryotic glycoprotein or glycolipid biosynthesis. The full sequence
      information can be easily retrieved from a databank, e.g. GenBank, using the
      relevant accession number(s).

PMID- 8563133
TI  - Biological and immunochemical characterization of recombinant human thyrotrophin.
AB  - Recombinant human thyroid-stimulating hormone (recTSH) has recently been
      engineered to detect metastatic lesions in patients operated on for thyroid
      cancer. In this report, we have compared the microheterogeneity, carbohydrate
      (CHO) content, mitogenic potency and immunoreactivity of the biotechnology
      product to those of human TSH of pituitary origin (pitTSH). Compositional
      analysis revealed that recombinant (rec) TSH produced in Chinese hamster ovary
      cells was overglycosylated compared with the native hormone (21 and 14%,
      respectively) with a higher amount of sialic acid and lack of N
      acetylgalactosamine. Electrofocusing followed by immunoblotting resolved recTSH
      into six glycoforms with pIs ranging from 6.0 to 8.6, which were converted to a
      major species of pI 8.9 by sialidase treatment. pitTSH contained five main
      isoforms of pI 6.5-8.2 distinct from those of recTSH and partially resistant to
      sialidase. Binding activity of both human TSHs to porcine thyroid membrane
      receptors was found to be similar, but recTSH appeared to be 20% active compared
      to pitTSH in eliciting cAMP production and cell growth in rat FRTL-5 cells.
      Immunoreactivity of the recombinant hormone was investigated using polyclonal and
      monoclonal antibodies raised against the native hormone or synthetic peptide
      sequences of its subunits. While rec- and pitTSH were recognized to a similar
      extent by anti-protein antibodies, they exhibited a different binding pattern to
      antipeptide antibodies. Serial dilution of anti-alpha 1-25, anti-alpha 26-51,
      anti-beta 96-112 antisera bound recTSH to a greater extent than pitTSH, while
      anti-beta 31-51 and anti-beta 53-76 displayed similar recognition toward both
      preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8563134
TI  - Catabolism of glycan moieties of lipid intermediates leads to a single Man5GlcNAc
      oligosaccharide isomer: a study with permeabilized CHO cells.
AB  - This paper presents kinetic and structural analyses of oligosaccharide material
      released during glycosylation in permeabilized Chinese hamster ovary cells
      incubated with sugar nucleotides. Permeabilized cells released 30 times more
      oligosaccharide material than metabolically labelled cells, normalized to the
      amount of labelled glycoprotein acceptor, making this an amenable system for
      study. Fifteen to forty per cent of the oligosaccharide material released by
      permeabilized cells was oligosaccharide-phosphate, depending on the nature and
      amount of the oligosaccharide-lipids synthesized. The oligosaccharide-phosphates
      released were recovered in the cytosol, and were exclusively Man2Glc-NAc2P and
      Man5GlcNAc2P, released from oligosaccharide-lipids thought to be facing the
      cytosol. In contrast, the structures found as neutral oligosaccharide material
      were similar to those attached to newly synthesized glycoproteins, indicating
      that the oligosaccharides were subjected to the same processing enzymes whether
      or not they were protein bound. Importantly, the kinetics of the transfer to
      protein and the release of free neutral oligosaccharide were parallel, suggesting
      that the same enzyme was responsible for both processes. Structural analyses
      demonstrated that the same Man5GlcNAc2 structure was transferred to protein and
      released as free oligosaccharide. Neutral oligosaccharides were found in both the
      cytosol and the pellet; however, oligosaccharides with one GlcNAc residue at the
      reducing end (OS-Gn1) were found exclusively in the supernate. The major neutral
      oligosaccharide produced after 2 h of metabolic labelling was Man5GlcNAc and it
      was found in the cytosol.

PMID- 8563135
TI  - Influence of D-galactosamine on the synthesis of sugar nucleotides and
      glycoconjugates in rat hepatocytes.
AB  - Rat hepatocytes were incubated in the presence of a high concentration of the
      hepatopathogenic agent D-galactosamine (GalN), and the effect on the cellular
      concentrations of pyrimidine nucleotides and nucleotide sugars was determined.
      The UTP pool became depleted. The pools of UMP and CMP in RNA decreased to 72%,
      indicative for an inhibition of RNA synthesis. UDP-HexNAc (where HexNAc is
      GlcNAc+GalNAc) and UDP-HexN (where HexN is GlcN+GalN) levels increased, and those
      of UDP-hexose and UDP-GlcA (where GlcA is glucuronic acid) decreased. The
      cellular concentration of CTP did not change, whereas that of CMP-NeuAc (where
      NeuAc is N-acetylneuraminic acid) showed a 2-fold increase. Labelling with
      [14C]orotic acid and [3H]cytidine showed that the metabolic flow via the de novo
      pathway was not changed. The depletion of the so-called overflow pool of UTP
      [Pels Rijcken et al., Biochem. J., 293, 207-213, 1993] caused a release of the
      feedback inhibition by UTP and thus an increased flow through the salvage
      pathway. Finally, it appeared that GalN, when added to hepatocytes, gives rise to
      a pool of UDP-GlcNAc (where GlcNAc is N-acetylglucosamine) that is separate from
      the pool of UDP-GlcNAc that is derived from GlcN.

PMID- 8563136
TI  - Abnormal synthesis of dolichol-linked oligosaccharides in carbohydrate-deficient
      glycoprotein syndrome.
AB  - Carbohydrate-deficient glycoprotein syndrome (CDGS) is a rare metabolic disorder
      presenting in infancy with severe neurologic involvement and variable
      multisystemic abnormalities. Diagnosis relies upon the detection of abnormal
      serum glycoprotein isoforms on isoelectric focusing (IEF) gels. Carbohydrate
      structural analyses were performed on the N-linked oligosaccharides of serum
      alpha 1-antitrypsin (alpha-1AT) from two Danish children with classical type I
      CDGS. Following preparative gel electrophoresis of alpha-1AT isoforms,
      oligosaccharide charge and monosaccharide composition analyses revealed increased
      glycosylation heterogeneity in CDGS compared with normal alpha-1AT. CDGS alpha
      1AT isoforms bore N-glycans co-migrating with monosialylated standards, while
      normal alpha-1AT oligosaccharides co-migrated with both mono- and disialylated
      standards. While the monosaccharide contents of normal alpha-1AT isoforms were
      relatively uniform, those of CDGS alpha-1AT isoforms varied widely, and many were
      relatively mannose enriched. The mannose-rich oligosaccharides of CDGS alpha-1AT
      were not typical oligomannose structures since they were not released by endo
      beta-N-acetylglucosaminidase H (endo H) digestion. Metabolic labelling of CDGS
      fibroblasts with [3H]mannose showed lower than normal intracellular total
      mannose, free mannose and phosphorylated mannose species, as well as diminished
      [3H]mannose incorporation into dolichol-linked and protein-linked
      oligosaccharides. In addition, the glycans liberated from CDGS dolichol-linked
      oligosaccharides were significantly truncated compared with those from normal
      fibroblasts. These data suggest that our type I CDGS patients produce abnormal N
      linked oligosaccharides due to impaired biosynthesis of dolichol-oligosaccharide
      precursors.

PMID- 8563137
TI  - Genomic organization and the 5'-upstream sequence of the rat cytosolic sialidase
      gene.
AB  - We have previously cloned a cDNA of a rat cytosolic sialidase which is strongly
      expressed in skeletal muscle. Both the highest enzyme activity, as well as the
      highest mRNA level, are present in this tissue. To understand the basis of the
      expression of this sialidase, we have cloned and sequenced the rat gene and its
      5'-upstream region from a rat genomic library. The gene encoding the 1.8 kb
      skeletal muscle mRNA was found to span 3.4 kb of genomic DNA, and to consist of
      two introns and three exons. Exon 1 contains the 5' noncoding region, and exons 2
      and 3 encode the regions containing the AUG initiation codon and two Asp-boxes,
      respectively. In the 5'-upstream sequence, there are a TATA box and two E-box
      pairs known as consensus binding sites for muscle-specific transcription factors.
      Analysis of the expression of transfected sialidase enhancer/promoter expression
      plasmid demonstrated the sialidase enhancer/promoter to be active in rat L6
      myogenic cells shown to express this gene, but inactive in rat 3Y1 fibroblasts
      shown not to express the enzyme. The transcription activity was increased 3-fold
      after induction of myoblast differentiation by serum depletion. These
      observations give an account of constitutive expression of the sialidase gene in
      skeletal muscle.

PMID- 8563138
TI  - Microheterogeneity of N-glycosylation on a stylar self-incompatibility
      glycoprotein of Nicotiana alata.
AB  - Gametophytic self-incompatibility, a mechanism that prevents inbreeding in some
      families of flowering plants, is mediated by the products of a single genetic
      locus, the S-locus. The products of the S-gene in the female sexual tissues of
      Nicotiana alata are an allelic series of glycoproteins with RNase activity. In
      this study, we report on the microheterogeneity of N-linked glycosylation at the
      four potential N-glycosylation sites of the S2-glycoprotein. The S-glycoproteins
      from N.alata contain from one to five potential N-glycosylation sites based on
      the consensus sequence Asn-Xaa-Ser/Thr. The S2-glycoprotein contains four
      potential N-glycosylation sites at Asn27, Asn37, Asn38 and Asn 150, designated
      sites I, II, IV and V, respectively. Site III is absent from the S2-glycoprotein.
      Analysis of glycopeptides generated from the S2-glycoprotein by trypsin and
      chymotrypsin digestions revealed the types of glycans and the degree of
      microheterogeneity present at each site. Sites I (Asn27) and IV (Asn138) display
      microheterogeneity, site II (Asn37) contains only a single type of N-glycan, and
      site V (Asn150) is not glycosylated. The microheterogeneity observed at site I on
      the S2-glycoprotein is the same as that observed at the only site, site I, on the
      S1-glycoprotein (Woodward et al., Glycobiology, 2, 241-250, 1992). Since the N
      glycosylation consensus sequence at site I is conserved in all S-glycoproteins
      from other species of self-incompatible solanaceous plants, glycosylation at this
      site may be important to their function. No other post-translational
      modifications (e.g. O-glycosylation, phosphorylation) were detected on the S2
      glycoprotein.

PMID- 8563139
TI  - Sialylation of intestinal microvillar membranes in newborn, sucking and weaned
      pigs.
AB  - Affinity cytochemistry and biochemistry revealed distinctive temporal changes in
      the expression of sialylated and compositionally related membrane glycoconjugates
      in the pig small intestine between birth and weaning. The expression of membrane
      NeuAc alpha 2,6 moieties, recognized by Sambucus nigra agglutinin-1, was high in
      newborn pigs, declined slightly during sucking and was very low in weaned
      animals. Conversely, the expression of membrane NeuAc alpha 2.3 moieties,
      recognized by Maackia amurensis agglutinin-2, was low at birth but higher in
      sucking and weaned animals. Histoblood group O- and A-antigen expression was
      first detected in a minority of sucking pigs, but was evident in all weaned pigs
      examined. Lactase glycoforms were isolated from solubilized microvillar membranes
      of newborn and weaned pigs. The newborn (predominantly alpha 2,6-sialylated) and
      weaned (predominantly alpha 1,2-fucosylated) glycoforms exhibited similar
      specific activity, indicating that postnatal lactase decline in the pig intestine
      is unrelated to temporal changes in membrane sialylation and fucosylation.

PMID- 8563140
TI  - Complex asparagine-linked oligosaccharides in Mgat1-null embryos.
AB  - To investigate the developmental role of complex N-linked oligosaccharides, we
      previously inactivated the mouse Mgat1 gene which encodes UDP-N
      acetylglucosamine: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I
      (GlcNAc-TI). Mgat1-null embryos developed morphogenic abnormalities by embryonic
      day (E) 9.5 and failed to survive beyond E10.5. Prior to E8.5, mutant and wild
      type embryos were phenotypically indistinguishable, raising the unexpected
      possibility that earlier embryonic development may not require complex N-glycans.
      We have now used in situ RNA hybridization to assess the temporal and spatial
      pattern of Mgat1 expression in normal embryos, and lectin histochemistry to
      determine whether Mgat1-null embryos lack complex N-glycans at pre-E9.5
      developmental stages. In situ RNA analysis indicated that Mgat1 transcripts
      normally increase dramatically between E7.0 and E9.5, 1-2 days prior to the death
      of mutant embryos. However, apparently normal levels of complex N-glycans were
      observed in E3.5 pre-implantation Mgat1-null embryos prior to declining to
      undetectable levels by E7.5. Complex N-glycans were not observed in E7.5-E9.5
      Mgat1-null embryos with the notable exception of vesicular structures within
      cells of the visceral extra-embryonic endoderm, perhaps reflecting the ability of
      these cells to take up and transport maternally derived glycoproteins. Mgat1-null
      embryos appear to complete pre-implantation development in the presence of
      maternally derived complex N-glycans, and may die at later stages, post E7.5,
      when a requirement for embryonically derived complex N-glycans arises.

PMID- 8563141
TI  - Galactofuranose-containing glycoconjugates in trypanosomatids.
AB  - Galactofuranose has been characterized in glycoinositolphospholipid (GIPL) anchor
      like structures having a glycerolipid or a ceramide, as in
      lipopeptidophosphoglycan (LPPG) of Trypanosoma cruzi, in the oligosaccharide core
      of lipopeptidophosphoglycan (LPG) of Leishmania species, and also modifying high
      mannose chains of trypanosomatid glycoproteins. Galactofuranose is usually
      present linked beta 1-->3 to Man, either as a terminal non-reducing unit, like in
      LPPG, or in the middle of the oligosaccharide core, as in LPG. The presence in
      protozoan parasites of galactose in the furanose configuration is a feature which
      deserves further attention since the mammalian hosts do not appear to produce
      glycoconjugates containing this structural unit. For that reason, hosts produce
      antibodies against galactofuranose, which may turn out to be important in
      understanding the pathogenesis and in the development of diagnostic methods. The
      metabolic pathways involved in the attachment to or removal of galactofuranose
      from glycoconjugates have not yet been elucidated. This is an area of incipient
      research, but of growing importance, since it will foster the design of
      inhibitors which may prove to be useful for the treatment of disease.

PMID- 8563142
TI  - Collectin in a non-mammalian species: isolation and characterization of mannan
      binding protein (MBP) from chicken serum.
AB  - A chicken serum lectin was isolated by affinity chromatography on TSK-75 beads
      derivatized with the monosaccharide N-acetyl-D-mannosamine (ManNAc). Serum was
      applied to the column in a Ca(2+)-containing buffer and proteins were eluted with
      EDTA. After recalcification, the eluate was passed through a new ManNAc
      derivatized column. Bound proteins were eluted with 50 mM ManNAc. Anti
      carbohydrate antibodies present in the eluate were removed by passage through a
      rabbit anti-chicken immunoglobulin derivatized column, and the lectin was further
      purified by ion-exchange chromatography and gel-permeation chromatography. The
      purified chicken lectin shows an overall structure similar to mammalian mannan
      binding protein (MBP). SDS-PAGE revealed two polypeptides of M(r) 33 and 34 kDa
      (reduced) with identical sequence for the first 30 NH2-terminal residues. The NH2
      terminal sequence shows 43% identity with the human MBP. Like mammalian MBP, the
      polypeptides of the chicken lectin are degraded by treatment with collagenase.
      Residues 26-30 (G-L-P(OH)-G-D) are likely to represent the beginning of the
      collagenous region. Mobilities on SDS-PAGE of the COOH-terminal collagenase
      resistant fragment under reduced and non-reduced conditions indicate the presence
      of intrachain disulphide bonds, as are also found in mammalian MBP. Gel
      chromatography showed an intact mol. wt of 750 kDa. Binding of the chicken MBP to
      mannan was inhibited by monosaccharides in the following order of potency: ManNAc
      > L-fucose > mannose > N-acetylglucosamine. Other monosaccharides inhibited
      poorly or not at all. Chicken MBP, bound to mannan, activated the classical
      complement pathway in human serum. Electron micrographs show structures and
      dimensions resembling human MBP. Overall, the results show that the purified
      lectin is the chicken homologue to mammalian MBP and indicate the presence of a
      MBP-like clearance system outside mammals.

PMID- 8563143
TI  - A new monoclonal antibody (3D3) generated with human respiratory mucins and
      directed against Lewis determinants.
AB  - We have prepared a monoclonal antibody (MAb), 3D3, raised against purified human
      respiratory mucins. This antibody recognized mucins and proteolytically derived
      glycopeptides. The epitope recognized by the antibody was destroyed by alpha-L
      fucosidase, indicating that it was present on the carbohydrate moieties.
      Structural specificity was determined by adsorption on a variety of synthetic,
      insolubilized oligosaccharides. Several lines of evidence indicate that the 3D3
      MAb reacted strongly with the Lewis (Leb) antigen, but also recognized Le(a) and
      Le(y) determinants. This antibody might be useful to study mucin secretion.

PMID- 8563144
TI  - Detection in human blood platelets of sialyl Lewis X gangliosides, potential
      ligands for CD62 and other selectins.
AB  - Activated platelets are known to express P-selectin, a lectin-like adhesion
      receptor (CD62), through which they bind to sialyl Lewis X (sLex) ligands
      displayed on the membranes of leukocytes. To determine whether direct platelet
      platelet interactions via P-selectin/sLex interactions are also possible, we have
      examined the ganglioside extract of human blood platelets for the presence of
      sLex ligands. Using the sensitive method of high-performance thin-layer
      chromatography (HPTLC)-immunostaining with the monoclonal antibody (mAb) CSLEX or
      with sialidase followed by mAbs MC480 or PM81, eight sLex bands were demonstrated
      at Rf 0.01, 0.03, 0.05, 0.06, 0.08, 0.10, 0.14 and 0.21 in the solvent 45:55:10
      chloroform-methanol-aqueous 0.02% CaCl2. The sensitivity of all eight bands to
      sialidase or endoglycoceramidase confirmed that they were gangliosides.
      Comparison of the HPTLC mobilities and densities of platelet bands with those
      from five other human tissues (granulocytes, monoblasts, kidney, aortic
      endothelium and erythrocytes) in three different solvents revealed three major
      bands associated with platelets: 3 (Rf0.03), 6 (0.08) and 14 (0.21). Platelet
      bands were demonstrated not to have resulted from granulocyte contamination.
      Partial purification of platelet sLex gangliosides by high-performance liquid
      chromatography and their reaction with 14 oligosaccharide-specific mAbs (FH4,
      FH5, LM112-161, LM119-181, A5, 1B2, BR55-2, BE2, ES4, MC631, MH04, SH34, P001 and
      MC813-70) revealed that band 6 is a multifucosylated neolacto ganglioside and
      band 14 is a branched, disialo neolacto fucoganglioside. Platelet band 3 combined
      the features of both bands 6 and 14, and reacted differently than granulocyte
      band 3. These partial structures resemble gangliosides associated with adhesion
      in other cell systems. It is concluded that platelets express tissue-specific
      sLex gangliosides (sLex ligands). Thus, it is possible that platelet-platelet
      binding may be mediated at least partially through P-selectin/sLex interactions,
      especially after platelet activation.

PMID- 8563145
TI  - Peptides inhibit selectin-mediated cell adhesion in vitro, and neutrophil influx
      into inflammatory sites in vivo.
AB  - The selectins are cell adhesion molecules whose carbohydrate-binding domain (C
      type lectin) is thought to be involved in leukocyte adhesion to activated
      vascular endothelium in the inflammatory process. A series of peptides, based on
      a conserved region (48YYWIGIRK55-NH2) of the lectin domain of E-, L- and P
      selectins, were analysed for their ability to block selectin-mediated cell
      adhesion in vitro, and neutrophil infiltration into sites of inflammation in
      vivo. The peptides inhibited the adhesion of myeloid cells to recombinant forms
      of E- and P-selectin. The adhesion of myeloid cells to human endothelial cells,
      stimulated to express E-selectin, was also inhibited by the peptides. Finally,
      the peptides blocked the adhesion of lymphocytes, expressing L-selectin, to high
      endothelial venules in lymph nodes which contain the ligand for L-selectin. A
      clear structure-activity relationship was established when peptides of different
      amino acid chain lengths were tested in these assays. Peptides lacking tyrosine
      residues (e.g. WIGIR-NH2) at their amino terminus were poor inhibitors of
      selectin-mediated cell adhesion in vitro. The peptides that were found to be
      inhibitors of cell adhesion in vitro were also found to inhibit (up to 70%)
      neutrophil infiltration into sites of inflammation in a thioglycollate-induced
      peritonitis mouse model system. They also significantly reduced (> 50%) the
      migration of neutrophils into cytokine-treated skin. These results strongly
      suggest that compounds based on these tyrosine-containing, selectin-derived
      peptides could be used as anti-inflammatory therapeutic agents.

PMID- 8563146
TI  - Characterization of asparagine-linked oligosaccharides on a mouse submandibular
      mucin.
AB  - The asparagine-linked oligosaccharides from an adult female mouse submandibular
      gland mucin were released by treatment with peptide-N4-(N-acetyl-beta
      glucosaminyl)asparagine amidase F or endo-beta-N-acetylglucosaminidase H. Endo
      beta-N-acetylglucosaminidase H appeared to be more effective at releasing the
      asparagine-linked oligosaccharides from this mucin than was peptide-N4-(N-acetyl
      beta-glucosaminyl)-asparagine amidase F. After quantitative reductive labelling
      with the fluorophore, 8-aminonaphthalene-1,3,6-sulphonic acid, the
      oligosaccharides were separated by polyacrylamide gel electrophoresis and
      isolated. The individual oligosaccharides were sequenced by a battery of
      recombinant exoglycosidases. Approximately 50% of the oligosaccharides were of
      the high-mannose type. The five-mannose member of this family was the most
      prevalent. The second group of oligosaccharides were of the non-bisected hybrid
      type. No complex asparagine-linked oligosaccharides were detected. The hybrids
      exhibited both biantennary and triantennary branching patterns. The triantennary
      hybrid was the most common hybrid at > 30% of all oligosaccharides. With
      approximately 98% of the hybrid oligosaccharides sialylated and all lacking a
      bisecting N-acetylglucosamine, these oligosaccharides as a group have been only
      rarely observed in other glycoproteins. The fully sialylated triantennary hybrid
      may be unique.

PMID- 8563147
TI  - Overexpression and purification of non-glycosylated recombinant endo-beta-N
      acetylglucosaminidase F3.
AB  - The gene for endo-beta-N-acetylglucosaminidase F3 was cloned into the high
      expression vector pMAL c-2, and expressed in Escherichia coli as a fusion
      protein. A key step in the purification employed Poros II (HS) chromatography,
      which greatly facilitated isolation of the enzyme from crude intracellular
      lysates. The unfused enzyme was recovered following digestion with Factor Xa and
      was isolated in a homogeneous form. The enzyme is non-glycosylated and fully
      active, and is a very useful analytical tool for investigating the structure of
      asparagine-linked glycans, especially those with core-substituted alpha 1,6
      fucosyl residues.

PMID- 8563148
TI  - A novel beta-galactosidase gene isolated from the bacterium Xanthomonas manihotis
      exhibits strong homology to several eukaryotic beta-galactosidases.
AB  - The gene encoding a beta-galactosidase from Xanthomonas manihotis was cloned into
      Escherichia coli. The gene resides on a 2.4 kb DNA fragment which was isolated
      from a partial Sau3A library in the cloning vector pUC19 using 5-bromo-4-chloro-3
      indolyl-beta-D-galactopyranoside (X-gal) as the selection. The enzyme produced by
      the clone has a specificity for beta 1-3- > beta 1-4-linked galactose. The
      nucleotide sequence of the gene was determined. The deduced protein sequence
      contained 597 amino acids yielding a monomeric molecular mass of 66 kDa. The
      cloned beta-galactosidase showed no similarity to any known prokaryotic beta
      galactosidase. However, extensive similarity was observed with eukaryotic beta
      galactosidases from animals, plants and fungi. The strongest similarity was with
      the beta-galactosidases found in the human and mouse lysosomes (42 and 41%
      identity, respectively). Alignment of the X.manihotis and eukaryotic beta
      galactosidase sequences revealed seven highly conserved domains common to each
      protein. Additionally, Domain 1 in X.manihotis showed similarity to regions
      within catalytic domains from seven xylanases and cellulases belonging to family
      10 of glucosyl hydrolases. A region spanning Domain 2 showed similarity to the
      catalytic domain of endo beta 1-3 glucanases from tobacco and barley.

PMID- 8563149
TI  - A precise structural analysis of a fertilization-associated carbohydrate-rich
      glycopeptide isolated from the fertilized eggs of euryhaline killi fish (Fundulus
      heteroclitus). Novel penta-antennary N-glycan chains with a bisecting N
      acetylglucosaminyl residue.
AB  - A novel carbohydrate-rich sialoglycopeptide of apparent molecular mass
      approximately 6 kDa was isolated from the fertilized eggs of Fundulus
      heteroclitus (euryhaline killi fish). This glycopeptide is a member of the L
      hyosophorin family, characterized by its high content of carbohydrate (80-90% by
      weight) and formed by depolymerization of the precursor glycopoly-protein (H
      hyosophorin) upon fertilization. The structures of the N-glycan chains were
      unambiguously established by a combination of compositional analysis, methylation
      analysis, selective chemical degradation (periodate oxidation-Smith degradation
      and hydrazinolysis-nitrous acid deamination), enzymatic (peptide:N-glycosidase F,
      several beta-galactosidases, beta-hexosaminidase and alpha-galactosidase)
      digestions and instrumental analyses (1H-NMR and fast atom bombardment mass
      spectrometry) to have the novel and unique carbohydrate sequences, Gal alpha 1-
      >3(Gal beta 1-->4)Gal beta 1-->4GlcNAc beta 1--> and Gal alpha 1-->3(+/- GalNAc
      beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4)Gal beta 1-->4GlcNAc beta 1-->. This
      study represents the first detailed investigation of the nature of bulky complex
      asparagine-linked penta-antennary glycans with a bisecting GlcNAc residue in
      glycoproteins. Expression of such bulky multiantennary glycan units on proteins
      may be essential during early embryogenesis.

PMID- 8563150
TI  - A sialidase activity in the midgut of the insect Triatoma infestans is
      responsible for the low levels of sialic acid in Trypanosoma cruzi growing in the
      insect vector.
AB  - Trypanosoma cruzi expresses a unique trans-sialidase that is responsible for the
      transfer of sialic acid from host glycoproteins and glycolipids to mucin-like
      glycoprotein acceptors on the parasite surface. The enzyme and the sialic acid
      acceptors are present in the mammalian forms of the parasite and in the parasite
      forms that grow in axenic cultures, which correspond to the developmental stages
      found in the insect vectors. Here we show that parasite forms growing in the
      vector Triatoma infestans express trans-sialidase in the hindgut portions of the
      insect. However, the sialic acid acceptors are poorly sialylated due to the low
      concentration of sialic acid donors in the gut lumen of T.infestans, which feeds
      exclusively on blood that is rich in sialic acid donors. These low levels of
      sialic acid donors are due to a novel sialidase activity present mainly in the
      anterior midgut with high specificity for alpha-2,3-sialyllactose, but not for
      alpha-2,6-sialyllactose. The activity is present in starved insects or insects
      fed with culture medium, indicating that it did not originate from the blood
      meal. Enzyme activity does not decrease in insects fed with antibiotics, is
      present in the salivary glands, and the few bacteria isolated from the gut and
      faeces of T.infestans did not display sialidase activity, indicating that the
      enzyme is not derived from a commensal organism. This novel activity could have a
      nutritional role in the gut of haematophagous insects and indicates that
      acquisition of sialic acid is not required for parasite development in the gut of
      T.infestans.

PMID- 8563151
TI  - Proliferation-dependent differential regulation of the dolichol pathway genes in
      Saccharomyces cerevisiae.
AB  - The dolichol pathway serves in the synthesis of the dolichol-linked
      oligosaccharide precursor for protein N-glycosylation. Recently, we reported that
      mRNAs of genes that function at the early steps in the dolichol pathway in yeast,
      ALG7, ALG1 and ALG2, were co-ordinately induced following growth stimulation of
      G0-arrested cells in a manner similar to that of the transcripts of the early
      growth response genes (Kukuruzinska, M.A. and Lennon, K. Glycobiology, 4, 437
      443, 1994). To determine whether the entire dolichol pathway was co-ordinately
      regulated with growth, we examined the expression of genes functioning late in
      the pathway, including two genes encoding oligosaccharyltransferase subunits, at
      two critical control points in the G1 phase of cell cycle: G0/G1 and START. We
      show that early in G1, at the G0/G1 transition point, the late ALG genes and the
      two oligosaccharyltransferase-encoding genes examined were regulated co
      ordinately with the early ALG genes: they were downregulated upon exit from the
      mitotic cell cycle into G0, and they were induced following growth stimulation in
      the absence of de novo protein synthesis. All the dolichol pathway genes produced
      transcripts with short half-lives that were rapidly stabilized in the presence of
      cycloheximide. In contrast, cell division arrest late in G1, at START, was
      accompanied by a selective downregulation of only the first dolichol pathway
      gene, ALG7, and not of the genes functioning later in the pathway. These results
      indicate that, depending on their position in G1, cells either co-ordinately or
      differentially regulate the dolichol pathway genes.

PMID- 8563152
TI  - Bone mineral density of the lumbar spine in patients with ossification of the
      posterior longitudinal ligament of the cervical spine.
AB  - Bone mineral density (BMD) of the lumbar spine in patients with ossification of
      the posterior longitudinal ligaments of the cervical spine (OPLL) was measured to
      elucidate the relation of spinal ossification with systemic hyperostotic
      condition. BMD in the lateral projection had a statistically significant
      correlation with that in the anteroposterior projection, and the former was
      considered to reflect the condition more accurately than was the latter, which
      may include the ossified spinal ligaments. BMD of patients with continuous and
      mixed types of OPLL was higher than that of those with the segmental type.
      Patients with OPLL and ossification of the other spinal ligaments had higher BMDs
      than did those without ossification. These results suggest that the BMD of the
      lumbar spine may reflect the systemic hyperostotic tendency and advancement of
      the ossification.

PMID- 8563153
TI  - Measuring treatment effects on repetitive lifting for patients with chronic low
      back pain: speed, style, and coordination.
AB  - The purpose of this study was to determine changes in the amount of work
      performed and lifting speed, style, and coordination during a repetitive dynamic
      lifting task for patients with chronic low back pain (CLBP) after an intensive 3
      1/2-week pain rehabilitation program. Subjects included 57 CLBP patients and an
      age- and gender-matched control group (n = 57). Patients' work indices increased
      by 71%, but remained significantly less than those observed for controls.
      Similarly, their lifting speed also increased significantly after treatment, but
      remained slower than the lifting speed of controls. Patients' posttreatment
      coordination indices, however, were not significantly different from those of
      controls. This finding suggests that treatment effectively normalized the dynamic
      lifting motion used by the patients. These findings, along with the basic
      kinematic patterns developed in this study, have important implications for
      determining improvements in functional capacity in the treatment of patients with
      CLBP.

PMID- 8563154
TI  - Anatomic considerations for dorsal sacral plate-screw fixation.
AB  - Five cadaveric pelves and 40 dry bony specimens were used to assess the
      feasibility of the lumbosacral plate fixation extending to beyond the S1 region
      and quantitatively to evaluate the posterior sacroiliac region and the dimensions
      of S1 and S2 pedicle and lateral mass. Partial removal of the posterior ilium was
      undertaken to measure the surface area available for plate fixation on the dorsal
      aspect of the sacrum. The results showed that the average distances between the
      outer edges of S1 and S2 dorsal foramina and the medial edge of the posterior
      ilium increased from 11.3 mm before removal of a portion of the medial posterior
      ilium to 16.6 mm after removal at the S1 level, and from 8.4 mm before removal of
      partial medial posterior ilium to 13 mm after removal at the S2 level,
      respectively. The average depths of the S1 and S2 pedicles were 37.1 and 32.2 mm
      in the direction anteromedial to the sagittal plane, respectively. The average
      depths of the S1 and S2 lateral mass were 37.3 and 33.9 mm in the direction
      anterolateral to the sagittal plane, respectively. In cases of vertebral
      metastases or osteoporosis, plating extending to S2 may be needed if good bony
      purchase cannot be achieved by the S1 pedicle or lateral mass screw. This study
      suggested also that partial removal of the posterior ilium enhances the space on
      the posterior aspect of the sacrum without severe compromise of the sacroiliac
      joint.

PMID- 8563155
TI  - Surgical management of lumbar neuropathic spinal arthropathy (Charcot joint)
      after traumatic thoracic paraplegia: report of two cases.
AB  - Two cases of successful surgical treatment of neuropathic spinal arthropathy
      (Charcot joint) are reported. Each patient was first seen several years after
      traumatic paraplegia. One patient had progressive kyphosis and the other had
      severe pain. Symptoms were relieved in both patients after interbody fusion and
      posterior fixation by using the lateral extracavitary approach to the spine. Both
      patients remain symptom free several years after the surgery. Fusion should be
      performed in symptomatic patients with neuropathic spinal arthropathy: this can
      be combined with posterior fixation in a single stage by using the lateral extra
      cavitary approach.

PMID- 8563156
TI  - Paraparesis after rib penetration of the spinal canal in neurofibromatous
      scoliosis.
AB  - Paraplegia or paraparesis is uncommon in patients with neurofibromatous
      scoliosis. The main causes of spinal cord compression in neurofibromatosis are
      vertebral angulation, vertebral subluxation, and tumorous lesions around the
      spinal cord. We report a rare case of paraparesis due to spinal cord compression
      by a rib penetrating the spinal canal in a patient with neurofibromatous
      scoliosis. There was complete recovery after laminectomy and proximal resection
      of the compressing rib along with combined anterior and posterior spinal fusion.

PMID- 8563157
TI  - The treatment of thoracolumbar fractures: one point of view.
AB  - Although much has been written regarding treatment of thoracolumbar fractures,
      questions remain concerning even the most basic issues. This article reviews
      classification systems, bony stability, the need for neural decompression in
      thoracolumbar spine fractures, and the literature comparing conservative
      treatment versus surgical treatment and evaluating various surgical approaches
      and fixation devices. Finally, data in the available literature and the results
      of the neurologic examination, radiographic studies, and the magnetic resonance
      imaging scan are used as the basis for a proposed classification system and a
      treatment algorithm.

PMID- 8563158
TI  - Different surgical approaches to far lateral lumbar disc herniations.
AB  - In far lateral disk surgery, although total facetectomy provides the best
      exposure and allows for removal of medial and far lateral extruded disk
      fragments, the risk of instability is increased as a result of excision of the
      pars interarticularis, Medial facetectomy uncovers the lateral and subarticular
      recess and preserves stability but does not allow for proper visualization of the
      far lateral compartment. The isolated extraforaminal approach provides access
      only to far lateral sequestrated fragments and does not allow access for more
      medial diskectomy or decompression of associated stenosis. Combining the
      extraforaminal exposure with a laminotomy, hemilaminectomy, or laminectomy
      complements the intertransverse (ITT) approach and affords access both to lateral
      and to medial disk lesions and stenotic abnormalities. The advantages and
      disadvantages of the less popular extraforaminal, transpars, percutaneous, and
      anterior decompressive techniques are also assessed. No one technique of far
      lateral disk excision is applicable for the management of all lesions. It is more
      appropriate to choose the right operation for the right patient.

PMID- 8563159
TI  - A surgeon's perspective of medical device regulation.

PMID- 8563160
TI  - Public citizen opposition to spinal implant fixation.

PMID- 8563161
TI  - Recent medical-legal proceedings and their effect on the practice of medicine in
      Chicago.
AB  - Since January 1994, northern Illinois has experienced a significant increase in
      litigation, which has been directly related to the lack of FDA approval of
      pedicle screw devices, and the adverse media attention to the FDA's actions.
      These activities coupled with those of the Public Citizen Health Research Group's
      have had a chilling effect on the practice of medicine. This is unwarranted,
      Congress has never provided the FDA with the authority to regulate the practice
      of medicine; and the FDA has reiterated that it lacks the intent or ability for
      such regulation. Medical science continues to outpace the regulatory process, and
      therefore it will remain the science of medicine that determines the standard of
      care.

PMID- 8563162
TI  - Whistler report: a survey of current indications for spinal instrumentation.

PMID- 8563163
TI  - Spinal metallic fixation--anterior and posterior.

PMID- 8563164
TI  - Effects of posterior instrumentation on axial rotation of the lumbar spine: an in
      vitro biomechanical study.

PMID- 8563165
TI  - Mouse tetranectin: cDNA sequence, tissue-specific expression, and chromosomal
      mapping.
AB  - Tetranectin is a plasminogen-binding tetrameric protein originally isolated from
      plasma. Expression of tetranectin appears ubiquitous, although particularly high
      expression is noted in the stroma of malignant tumors and during mineralization.
      To dissect the molecular basis of tetranectin gene regulation, mouse tetranectin
      cDNA was cloned from a 16-day-old mouse embryo library. Sequence analysis
      revealed a 992-bp cDNA with an open reading frame of 606 bp, which is identical
      in length to the human tetranectin cDNA. The deduced amino acid sequence showed
      high homology to the human cDNA with 76% identity and 87% similarity at the amino
      acid level. Sequence comparisons between mouse and human tetranectin and some C
      type lectins confirmed a complete conservation in the position of six cysteines
      as well as numerous other amino acid residues, indicating an essential structure
      for potential function(s) of tetranectin. The sequence analysis revealed a
      difference in both sequence and size of the noncoding regions between mouse and
      human cDNAs. Northern analysis of the various tissues from mouse, rat, and cow
      showed the major transcript(s) to be approximately 1 kb, which is similar in size
      to that observed in human. Although additional minor bands of 1.5 and 3.3 kb were
      found in Northern blots, RT-PCR (reverse transcription polymerase chain reaction)
      analysis failed to provide evidence that these minor bands are products of the
      tetranectin gene. Finally, the genetic map location for this gene, Tna, was
      determined to be on distal mouse Chromosome (Chr) 9 by analysis of two sets of
      multilocus crosses.

PMID- 8563166
TI  - The germ cell deficient locus maps to mouse chromosome 11A2-3.
AB  - The autosomal recessive mouse mutation, germ cell deficient, gcd, manifests as
      infertility in both sexes owing to improper migration and/or proliferation of
      primordial germ cells during embryonic development. Mice harboring this mutation
      have been hypothesized to be animal models of the human syndromes, premature
      ovarian failure and Sertoli cell only syndrome. Since the gcd mutation arose from
      the insertion of over 100 kb of foreign DNA into the chromosome during a
      transgenic mouse experiment, fluorescent in situ hybridization with the transgene
      as a probe was used to determine the chromosomal position of the gcd locus. DAPI
      chromosomal banding in conjunction with double labeling with the alpha 1(I)
      collagen gene revealed that the gcd locus is situated on mouse Chromosome (Chr)
      11A2-3. Two candidate genes, Lif and Oncostatin M, map near the gcd locus;
      however, Southern blot hybridization analysis revealed no gross rearrangements in
      these genes in gcd mice. The chromosomal position of the gcd locus will prove
      valuable in the search for other candidate genes as well as a landmark for
      positional cloning experiments.

PMID- 8563167
TI  - Nhlh1, a basic helix-loop-helix transcription factor, is very tightly linked to
      the mouse looptail (Lp) mutation.
AB  - Looptail (Lp) is a mutation on the distal portion of mouse Chromosome (Chr) 1
      that affects neurulation in mouse and is phenotypically expressed by appearance
      of an open neural tube along the entire antero-posterior axis of the embryo
      (craniorachischisis). Nhlh1, a member of the basic helix-loop-helix family of
      transcription factors, is expressed in the developing neural tube in structures
      affected by the Lp mutation and has been regionally assigned to the distal part
      of mouse Chr 1. Using a large panel of looptail animals from an (Lp/+ x SWR/J)F1
      x SWR/J segregating backcross progeny, we have determined that Nhlh1 maps very
      close to Lp, with no recombinant detected in 500 informative animals tested; both
      map within a 0.6-cM segment defined as D1Mit113/Apoa2/Fcer1 gamma-(0.4 cM)
      Nhlh1/Lp-(0.2 cM)-Fcer1 alpha/D1Mit149/Spna1. Nucleotide sequencing of Nhlh1 cDNA
      clones from wild type (WT) and Lp/Lp embryos failed to identify sequence
      alterations associated with the mutant phenotype. Southern hybridization of
      genomic DNA from WT and Lp/Lp embryos failed to identify specific rearrangements
      at or near the Nhlh1 locus, and Northern RNA blotting and RT-PCR evaluation of
      Nhlh1 mRNA expression indicated that both the levels and types of Nhlh1 mRNAs
      produced in WT and Lp/Lp embryos were indistinguishable. These studies suggest
      that Nhlh1 and Lp are not allelic. Nevertheless, Nhlh1 is the Chr 1 marker most
      tightly linked to Lp identified to date and can, therefore, be used as an
      excellent entry probe to clone the Lp region.

PMID- 8563168
TI  - Chromosomal and regional localization of the loci for IGKC, IGGC, ALDB, HOXB,
      GPT, and PRNP in the American mink (Mustela vison): comparisons with human and
      mouse.
AB  - Chromosomal localization of the genes for gamma- and kappa-immunoglobulins (IGGC
      and IGKC, respectively), aldolase B (ALDB), prion protein (PRNP), homeo box B
      (HOXB), and glutamate pyruvate transaminase (GPT) were determined with the use of
      mink-rodent hybrid cells. Analysis of segregation of the mink markers and
      chromosomes in these hybrid cells allowed us to assign the gene for HOXB to
      Chromosome (Chr) 8, IGGC to Chr 10, PRNP and IGKC to Chr 11, ALDB to Chr 12, and
      GPT to Chr 14 in mink. Furthermore, using a set of mink-mouse hybrid cells
      carrying fragments of mink Chr 8 of different sizes, we assigned the gene for
      HOXB to the pter-p26 region of the short arm of Chr 8. Comparative mapping of the
      genes of mink, human, and mouse, as well as other mammalian species, demonstrated
      that the mink genes HOXB, PRNP, ALDB, and IGGC are members of a conserved region
      shared by many mammalian species in common; the IGKC gene is a member of a
      conserved region common to carnivores and primates, not rodents; the GPT gene is
      a member of a syntenic gene group probably unique to the Mustelidae family or
      carnivores.

PMID- 8563169
TI  - DNA marker-assisted selection of the polled condition in Charolais cattle.
AB  - Five Charolais families known to segregate for both horned and polled were
      selected and tested for linkage analysis by use of microsatellites and
      karyotyping for Robertsonian translocation 1;29. No recombinants were found
      between any of these markers and the polled phenotype or each other. When
      statistical analysis was performed, the logarithm of the odds (LOD) indicated
      that there was 100% linkage occurring between the markers and the phenotype (p <
      0.001). These microsatellite markers, TGLA49 and BM6438, can be assumed to be
      very close to the actual gene that determines the polled phenotype. Another
      linked marker, SOD1, was physically mapped, which places all of these markers
      within 1q12-14, very near the centromere of Chromosome (Chr) 1. A homozygous
      polled cow was identified in this study by following the alleles at both markers
      and the phenotypes in her family.

PMID- 8563170
TI  - A small-insert bovine genomic library highly enriched for microsatellite repeat
      sequences.
AB  - A bovine genomic phagemid library was constructed with randomly sheared DNA.
      Enrichment of this single-stranded DNA library with CA or GT primers resulted in
      45% positive clones. The 14% of positive clones with (CA.GT) > 12, and not
      containing flanking repetitive elements, were sequenced, and the efficiency of
      marker production was compared with random M13 bacteriophage libraries. Primer
      sequences and genotyping information are presented for 390 informative bovine
      microsatellite markers. The genomic frequency for 11 tri- and tetranucleotide
      repeats was estimated by hybridization to a lambda genomic library. Only GCT,
      GGT, and GGAT were estimated to have a frequency of > 100 per genome. Enrichment
      of the phagemid library for these repeats failed to provide a viable source of
      microsatellite markers in the bovine. Comparison of map interval lengths between
      100 markers from the enriched library prepared from randomly sheared DNA and M13
      bacteriophage libraries prepared from Mbo1 restriction digests suggested no bias
      in skeletal genomic coverage based on source of small insert DNA. In conclusion,
      enrichment of the bovine phagemid library provides a sufficient source of
      microsatellites so that small repeat lengths and flanking repetitive sequences
      common in the bovine can be eliminated, resulting in a high percentage of
      informative markers.

PMID- 8563171
TI  - A human ubiquitin conjugating enzyme, L-UBC, maps in the Alzheimer's disease
      locus on chromosome 14q24.3.
AB  - We have identified a novel ubiquitin conjugating enzyme gene, L-UBC, which maps
      to human Chromosome (Chr) 14q24.3. This is also the location of the major early
      onset familial Alzheimer's disease gene (FAD3). L-UBC encodes a protein that
      demonstrates homology to the yeast ubiquitin conjugating enzyme, UBC-4, and human
      UbcH5. Their functions are to ubiquitinate specific proteins targeted for
      degradation. The protein also exhibits very strong homology to a rabbit protein,
      E2-F1, which mediates p53 degradation driven by papilloma virus E6 protein in
      vitro. The accumulation of specific proteins that have undergone aberrant
      processing in neurofibrillary tangles and amyloid plaques is the classic
      pathological feature in brains of Alzheimer's disease patients. Abnormal
      ubiquitination has previously been suggested to play a role in the etiology of
      Alzheimer's disease. This gene therefore represents a plausible candidate gene
      for FAD3.

PMID- 8563172
TI  - Cloning of the murine homolog of the leukemia-associated PML gene.
AB  - PML, a Ring-finger protein, participates in the disruption of normal myeloid
      differentiation when fused to the retinoic acid receptor alpha (RAR alpha) by the
      translocation between chromosomes (Chrs) 15 and 17 in acute promyelocytic
      leukemia (APL). As an initial step in the characterization of PML in species
      other than human, a murine cDNA clone of the PML gene was isolated and sequenced,
      and the intron/exon organization of the murine locus determined. The predicted
      amino acid sequence of the mouse PML protein shows 80% similarity to that of its
      human homolog. However, the mouse and human proteins show greater than 90%
      similarity in the proposed functional domains of the proteins. Despite its role
      in the etiology of APL, PML expression is not detectably altered during
      granulocytic differentiation in a murine in vitro system. Chromosomal
      localization of the Pml locus by somatic cell hybrids and by linkage analysis
      indicates that the gene maps to a region of mouse Chr 9 with known linkage
      homology to the region on human Chr 15q to which PML has been localized.

PMID- 8563174
TI  - Chromosomal localization of the beta-adducin gene to mouse chromosome 6 and human
      chromosome 2.

PMID- 8563173
TI  - An anchored molecular map of mouse chromosome 6 with an analysis of interference.

PMID- 8563175
TI  - Genes for tensin, villin and desmin are linked on mouse chromosome 1.

PMID- 8563176
TI  - cDNA cloning of the rat APC gene and assignment to chromosome 18.

PMID- 8563177
TI  - Physical assignment of loci to sheep chromosome 7 confirms its homology to cattle
      chromosome 10.

PMID- 8563178
TI  - Cloning and chromosomal assignment of the bovine interleukin-2 receptor alpha (IL
      2R alpha) gene.

PMID- 8563179
TI  - An STS map of the limb girdle muscular dystrophy type 2A region.

PMID- 8563180
TI  - Genetic mapping of Ptprm on mouse chromosome 17.

PMID- 8563181
TI  - Mapping of the flaky skin (fsn) mutation on distal mouse chromosome 17.

PMID- 8563182
TI  - The gene encoding endothelial nitric oxide synthase, Nos3, maps to rat chromosome
      4.

PMID- 8563183
TI  - Linkage mapping of the endothelin-converting enzyme gene (Ednce) to rat
      chromosome 5.

PMID- 8563184
TI  - Localization of fucosyl-transferase gene to bovine and goat chromosome 7 and
      sheep chromosome 5.

PMID- 8563185
TI  - Hyperthermia and birth defects.

PMID- 8563186
TI  - Ethanol potentiates valproic acid-induced neural tube defects (NTDs) in mice due
      to toxicokinetic interactions.
AB  - Both the antiepileptic drug valproic acid (VPA) and ethanol interfere with fetal
      folate metabolism, which may contribute to their mechanism of teratogenesis.
      Therefore, the possible interaction between VPA and ethanol was investigated in
      mice. Ethanol (2 x 2.5 g/kg) was given orally 4 and 1 h prior to VPA (300 and 400
      mg/kg, SC) in day 8.25 pregnant NMRI mice. Fetuses were examined for exencephaly,
      embryolethality, and fetal weight retardation on day 18 of gestation. Higher
      doses of ethanol (2 x 5 g/kg, orally) at day 7.5 and 8 of gestation resulted in
      22% embryolethality and 1.7% exencephaly with no effect on fetal weight. Ethanol,
      however, increased VPA (400 mg/kg, SC)-induced exencephaly, embryolethality, and
      fetal weight retardation. It also increased VPA (300 mg/kg, SC)-induced
      exencephaly without affecting embryotoxicity. A minimum of two oral doses of 2.5
      g/kg ethanol, 1 and 4 h, or 1 and 6 h prior to VPA administration were needed to
      produce maximum potentiation of the effects observed. These ethanol doses
      increased plasma VPA levels of day 8.25 pregnant mice given 400 mg/kg VPA to
      values comparable to the levels of mice given only VPA at a higher dose level
      (500 mg/kg). The incidence of exencephaly was increased from 35% for VPA (400
      mg/kg) to 59% when VPA was given with ethanol. This incidence was similar to that
      of 60% for the high dose of VPA (500 mg/kg) administered without ethanol.
      Maternal plasma ethanol concentration peaked at 193, 196, and 183 mg/dL 15, 30,
      and 60 min, respectively, after oral ethanol administration (2.5 g/kg), and fell
      to 110 mg/dL by 2 h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8563187
TI  - Histochemical localization of retinoic acid receptors in the developing hamster
      fetus.
AB  - Retinoids have pleiotropic effects on animal development. The eventual targets of
      retinoids are retinoic acid receptors (RARs). Therefore, developmental expression
      patterns of RARs are important in elucidating the mechanisms of normal functions
      of retinoids and retinoid-induced teratogenesis. We developed monospecific
      polyclonal antibodies against hRAR alpha, hRAR beta, and mRAR gamma, to study the
      developmental expression of RARs in hamster fetus. There was high sequence
      homology across the species for each subtype of RARs and antibodies raised
      against human or mouse RARs reacted with hamster RARs. In addition, hamster cDNA
      of RARs, which can generate the whole length antisense RNA probe using a suitable
      vector, were also isolated from a 12-day-old hamster fetal library. Monospecific
      antibodies and antisense RNA probes were used to localize proteins and
      transcripts of RARs in the developing hamster fetus from day 8 to day 14. There
      was a widespread distribution of RAR proteins and transcripts in the developing
      fetus. Expression was abundant in neuroepithelium, branchial arch, cardiac
      linings, and primordial bone and cartilage tissues. Overlapping expression and
      redundancy of various RARs may be one of the safeguard mechanisms in retinoid
      homeostasis.

PMID- 8563188
TI  - Effects of tobacco smoke inhalation on the developing mouse embryo and fetus.
AB  - Pregnant C57BL or mutant curly tail mice were exposed to tobacco smoke in a
      smoking machine for 10 min, three times a day, either on the day of conception
      (day 0) and days 1 and 2, or on days 3, 4, and 5, or from day 0 through day 17.
      In the first two cases, the embryonic development was subsequently assessed on
      day 9. Both periods of exposure were associated with a dose-related retardation
      in embryonic growth, but it was more marked with exposure on days 0, 1, and 2. It
      would seem, therefore, that even brief episodes of maternal smoking are
      detrimental to the very early embryo, and even if smoking is stopped, the effects
      persist at least for some days and there is no immediate catch-up growth. In the
      mice exposed continuously for 17 days, the fetuses were studied on day 18: there
      was a significant reduction in fetal body weight in both types of mice. There was
      also a reduction in the number of skeletal ossification centres, showing that
      additionally, there was developmental delay. In C57BL mice, one rib abnormality
      occurred, but no major congenital malformations; however, in the curly tail
      mutants, 60% of which normally have a curly tail or an open neural tube defect,
      there was a modest increase in the frequency of open spina bifida and
      exencephaly. A few minor rib abnormalities also occurred, and one case of cleft
      lip with cleft palate. These results indicate that tobacco smoke, while
      detrimental to the developing fetus, is not a potent teratogen in the mouse, but
      that it may have minor effects in those individuals genetically predisposed to an
      abnormality. This may have implications for humans, and may explain the generally
      inconclusive findings regarding congenital malformations in the children of women
      who smoke during pregnancy. In all experiments, the detrimental effects were seen
      with both higher tar cigarettes (tar and nicotine yields: 12.9 and 1.19
      mg/cigarette, respectively) and lower tar cigarettes (4.8 and 0.54 mg/cigarette
      respectively), so tobacco modification is not really beneficial to the developing
      fetus.

PMID- 8563189
TI  - In vitro toxicity of 1,2-dibromo-3-chloropropane (DBCP) in different testicular
      cell types from rats.
AB  - 1,2-Dibromo-3-chloropropane (DBCP)-induced toxicity was studied in rat germ cells
      from different stages of spermatogenesis, separated by centrifugal elutriation,
      and in Sertoli cells prepared from sexually mature and immature animals. The in
      vitro metabolic activation of 50 to 250 microM DBCP, measured as covalent binding
      of 14C-DBCP to macromolecules, was highest in round spermatids, lowest in Sertoli
      cells and elongating/elongated spermatids, and intermediate in spermatocytes.
      High concentrations of DBCP (> or = 250 microM) caused a decrease in oxygen
      consumption and mitochondrial rhodamine 123 uptake, indicating an effect on
      mitochondrial function. Altered Sertoli cell function, measured as detachment of
      germ cells in Sertoli-germ cell cocultures, was evident at DBCP concentrations >
      or = 300 microM. DBCP-induced DNA damage occurred at much lower concentrations
      (10 to 30 microM) when compared to effects on mitochondrial function and Sertoli
      cell function. The extent of single strand DNA breaks and alkali-labile sites
      (ssDNA breaks) measured by the alkaline filter elution technique and the single
      cell gel electrophoresis assay, were greatest in the round spermatids >
      spermatocytes = Sertoli cells > elongating/elongated spermatids. The study
      demonstrates that various testicular cell types show differences in their rates
      of activation of DBCP to metabolites that bind to macromolecules. DNA is a more
      sensitive intracellular target in DBCP-induced testicular toxicity than
      mitochondria. Round spermatids appear to be more susceptible to DBCP-induced
      ssDNA breaks than spermatocytes, elongating/elongated spermatids, or Sertoli
      cells.

PMID- 8563190
TI  - Testicular toxicity of WIN 18446 in the laboratory mouse.
AB  - The effect of oral administration of N,N'=bis (dichloroacetyl)-1, 8
      octamethylenediamine (WIN 18446) (200 mg/kg body weight/day, up to 30 days) on
      the testis of the Parkes (P) strain laboratory mouse was studied. The drug caused
      reduction in testicular weight and severe atrophic changes in the seminiferous
      tubules. A duration-dependent effect of the drug was observed on the germ cells.
      The drug had its initial impact on spermatids followed by spermatocytes,
      ultimately culminating in the Sertoli cell-spermatogonia syndrome. The drug
      induced changes included exfoliation of germ cells, formation of multinucleated
      giant cells, and vacuolization of cytoplasm and displacement (towards the lumina
      of the tubules) of Sertoli cell nuclei. Even 75 days after drug withdrawal,
      testicular weight remained depressed and in 15 to 20% of the tubules there was
      incomplete recovery of spermatogenesis. Our data indicate that WIN 18446 induces
      sustained impairment of spermatogenesis by a direct action on spermatogonia or
      indirectly by affecting the integrity of the Sertoli cells. The Leydig cells
      remained unaffected in WIN 18446-treated mice.

PMID- 8563191
TI  - Nuclear alterations during acrosomal cap formation in spermatids of lead-treated
      rats.
AB  - Ultrastructural studies were conducted to assess the effect of lead (Pb 5 mg/kg
      IP for 16 days as lead acetate) on rat spermiogenesis. Results showed swelling of
      nuclei and acrosomes in round spermatids. In Sertoli cells, nuclei appeared
      fragmentated, whereas the cytoplasm exhibited a vacuolated appearance and a few
      structures delimitated by a double membrane that contain parallelly arranged
      microtubules and cross-striated fine fibrils. Sertoli cell tight junctions
      remained intact. There was no significant change in epididymal sperm motility and
      counts, although testicular and blood lead levels were found to be elevated after
      lead exposure. These results suggest that spermatid and Sertoli cell damage may
      lead to disruption of spermiogenesis in lead-intoxicated rats.

PMID- 8563192
TI  - Clomiphene-induced ovulation and the risk of neural tube defects.

PMID- 8563193
TI  - Influence of PCBs and PCDDs on preimplantation mouse embryo development.

PMID- 8563194
TI  - Reverse-phase high performance liquid chromatography and linear solvation energy
      relationship for studies of alkyl (1-phenylsulfonyl) cycloalkane-carboxylates.

PMID- 8563196
TI  - Arsenic levels in soil of a town polluted 35 years ago (Nakajo, Japan).

PMID- 8563195
TI  - Occurrence of nitrosatable amines in some Nigerian medicinal plants.

PMID- 8563197
TI  - Environmental contaminants in eggs of California least terns (Sterna antillarum
      browni).

PMID- 8563198
TI  - Natural and anthropogenic trace-metal input into the coastal and estuarine
      sediments of the straits of Malacca.

PMID- 8563199
TI  - Total and organic mercury in Barents Sea pelagic fish.

PMID- 8563200
TI  - Polychlorinated biphenyl (PCB) congeners in mussel and other mollusc from Da Chen
      Island, East China Sea.

PMID- 8563201
TI  - Effect of corn plants and rhizosphere populations on pesticide degradation.

PMID- 8563202
TI  - Possible reuse of treated municipal wastewater for Citrus spp. plant irrigation.

PMID- 8563203
TI  - Frequencies of sister chromatid exchanges in lymphocytes of Portland cement
      factory workers.

PMID- 8563204
TI  - Dose response effects of fluoride on resorption of deciduous teeth in young
      rabbits.

PMID- 8563205
TI  - Effect of chronic aluminum exposure on the levels of conjugated dienes and
      enzymatic antioxidants in hippocampus and whole brain of rat.

PMID- 8563206
TI  - Effects of Cr (VI) on ATPases in the brain and muscle of mudskipper,
      Boleophthalmus dentatus.

PMID- 8563207
TI  - Histopathological investigations of the effects of malathion on dwarf lizards
      (Lacerta parva, Boulenger 1887).

PMID- 8563208
TI  - Relation of allozyme genotype to survivorship of juvenile bream, Abramis brama
      L., acutely exposed to DDVP, an organophosphorus pesticide.

PMID- 8563209
TI  - Inhibition of acetylcholinesterase activity in the central nervous system of the
      red swamp crayfish, Procambarus clarkii, by mercury, cadmium, and lead.

PMID- 8563210
TI  - Responses of invertebrates and fish to alkyl sulfate and alkyl ethoxylate sulfate
      anionic surfactants during chronic exposure.

PMID- 8563211
TI  - Effect of aluminum and zinc on enzyme activities in the green alga Selenastrum
      capricornutum.

PMID- 8563212
TI  - Acute toxicity studies with earthworms, Lumbricus terrestris.

PMID- 8563213
TI  - Effect of two commercial formulations of Bacillus thuringiensis subsp. kurstaki
      (Dipel 8L and Dipel 8AF) on the Collembolan species Folsomia candida in a soil
      microcosm study.

PMID- 8563214
TI  - Effects of Mg2+, Co2+, and Hg2+ on the nucleus and nucleolus in root tip cells of
      Allium cepa.

PMID- 8563215
TI  - Effectiveness in adolescent health.

PMID- 8563216
TI  - The Finnish disease heritage: a personal look.

PMID- 8563217
TI  - The foetal pituitary, postmaturity and breech presentation.

PMID- 8563218
TI  - Risk of tumor recurrence and growth hormone therapy.

PMID- 8563219
TI  - Apnoea detection: human performance and reliability of a computer algorithm.
AB  - We examined the consistency of apnoea recognition between three human experts.
      The hypothesis was that computer detection of apnoea could emulate human expert
      apnoea recognition. The aim was to detect apnoeas with the highest possible
      accuracy from a single breathing signal, by both human experts and computer.
      Three human experts independently examined recordings of breathing wave-form from
      overnight sleep studies from 10 infants aged 3-17 weeks. All apnoeas of 5 s or
      more were identified and reviewed. However, there still remained 10%
      disagreement. A computer apnoea detector was implemented. An algorithm analysed
      statistical properties of the signal to find breathing pauses. Optimal
      performance was 1% missed apnoeas (compared with the agreed apnoeas identified by
      the three experts) and 29% false detections. This computer algorithm reliably
      identified most apnoeas but did not replace the human expert.

PMID- 8563220
TI  - Bone mineral content of young female former gymnasts.
AB  - Intense physical exercise and diet restriction could result in delayed puberty
      and have a negative influence on the acquisition of peak bone mass during
      puberty. Nineteen young women who had been in elite gymnastic training during
      their prepubertal and pubertal years were investigated with regard to their
      health, menstrual data and bone mineral areal mass (BMA). Twenty-one women of
      comparable age served as controls. The age of menarche of the "former" gymnasts
      and the controls was 14.8 +/- 1.8 and 12.1 +/- 1.4 years, respectively. Fourteen
      of the gymnasts had been or were using oral contraceptives (OCs) and most of the
      non-users now had regular menstrual periods. During the years preceding the
      study, physical activity among the "former" gymnasts had gradually declined.
      Although the gymnasts had had a delayed puberty, no difference was found in total
      body or spinal BMA compared to the healthy controls. Their normal BMA in early
      adulthood could reflect a catch-up due to a combination of decreasing athletic
      activity, normal menstrual cycles and intake of OCs.

PMID- 8563221
TI  - Serum lipids and apolipoproteins from 1 to 15 years: changes with age and
      puberty, and relationships with diet, parental cholesterol and family history of
      ischaemic heart disease.
AB  - We describe the pattern of change for serum lipids and apolipoproteins from 1 to
      15 years of age in a cohort of 128 children, supplemented with 215 children from
      11 years of age and 243 at 13 years of age. Total cholesterol (TC) decreased
      after infancy, increased in early puberty and then decreased to 15 years of age.
      Reciprocal changes in high (HDLC) and low (LDLC) density lipoprotein cholesterol
      occurred during each interval, with HDLC increasing from 13 to 15 years in both
      sexes. The correlation for TC between children of both sexes and mothers and
      fathers varied from 0.1 to 0.28 at 2-13 years. At 15 years of age the correlation
      between mothers: daughters increased to 0.31, decreased to 0.19 for fathers:
      daughters, but no association was present between either parent and their sons.
      There were no differences in mean lipid values for the sample grouped according
      to the extent of family history of early ischaemic heart disease (before 60 years
      of age). There were few significant associations between serum lipids, energy and
      nutrients. At 15 years of age inverse associations were present between TC and
      energy, protein, sugar, starch and fibre intakes, and a positive association with
      total fat intake.

PMID- 8563222
TI  - Profile of urinary bile acids in familial intrahepatic cholestasis with Coombs'
      negative haemolytic anaemia.
AB  - We present two male siblings with intrahepatic cholestasis and prolonged indirect
      hyperbilirubinaemia. Their familial intrahepatic cholestasis syndrome was
      characterized by Coombs' negative haemolytic anaemia, without giant cell
      transformation of hepatocytes and high concentrations of serum gamma-glutamyl
      transpeptidase and cholesterol. By gas chromatography-mass spectrometry, we
      detected large amounts of 1 beta-hydroxylated bile acids, especially 1 beta,3
      alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholan-24-oic acid (25.5-67.9% of
      total urine bile acids) in the urine during phenobarbital therapy. However, the
      amount of urinary 1 beta-hydroxylated bile acids gradually decreased as the
      disease progressed. At the end-stage, we detected large amounts of 7 alpha,12
      alpha-dihydroxy-3-oxochol-4-en-24-oic acid (19.6% of total urine bile acids). The
      ratio of 7 alpha,12 alpha-dihydroxy-3-oxochol-4-en-24-oic acid to cholic acid in
      the urine was 0.8. We conclude that in infants with end-stage liver failure, the
      microsomal hydroxylation of bile acids is impaired and the excretion of delta 4-3
      oxo bile acids is increased.

PMID- 8563223
TI  - Antiendomysium antibodies and coeliac disease: solved and unsolved questions. An
      Italian multicentre study.
AB  - A total of 3783 subjects were enrolled to compare IgA and IgG gliadin antibodies
      (AGA) with IgA endomysium antibodies (EMA) in coeliac disease (CD). Among 688
      children with untreated CD EMA were positive in 93.8%, IgA AGA in 84.9% and IgG
      AGA in 90.2%. AGA, but not EMA, sensitivity decreased with age. EMA were present
      in 3.8% of control subjects, IgA AGA in 14.9% and IgG AGA in 34.3%. Follow-up of
      5 of 39 EMA-positive controls showed flat mucosa. Combined determination of EMA
      and AGA showed an increased predictive value: if EMA and AGA were both positive,
      the mucosa was flat in 99.1%, if both were negative, the mucosa was normal in
      99.1%. After a gluten-free diet (GFD), IgA-AGA disappeared first. Among 21
      patients not on a strict GFD and in 194 coeliac patients after challenge, EMA,
      but not AGA, were always positive. Among 67 first-degree relatives of coeliacs,
      the positive predictive value of EMA was 90.6%, IgA AGA 74.3% and IgG AGA 44.6%.
      In conclusion, EMA screening is an excellent test for the diagnosis and follow-up
      of CD, and for identification of its silent and latent forms.

PMID- 8563224
TI  - Response to oral beta-carotene supplementation in patients with cystic fibrosis:
      a 16-month follow-up study.
AB  - The aim of this study was to determine the efficacy of long-term oral beta
      carotene supplementation for correcting impaired beta-carotene status in cystic
      fibrosis patients. Thirty-five patients (2.3-30.5 years of age) with coefficients
      of fat absorption of 46-96% (median 88%) received beta-carotene 0.5 mg/kg daily
      and were followed over a 16-month treatment period. Baseline plasma beta-carotene
      concentrations in patients (mean +/- SD, 0.09 +/- 0.06 mumol/l) were
      significantly lower than those of age-matched controls (0.86 +/- 0.56 mumol/l) (p
      < 0.0001). Concentrations increased rapidly and reached a plateau at or before 3
      weeks that was maintained throughout the study period. Values obtained at 3 weeks
      (0.89 +/- 0.64 mumol/l) were significantly higher (p < 0.0001) than those at
      baseline and did not differ from controls. Plasma retinol and alpha-tocopherol
      concentrations increased during the observation period, but remained within
      normal ranges. Plasma retinyl palmitate, which was below the detection limit in
      all but one patient at baseline, did not increase. Thus oral beta-carotene
      supplementation is effective and normalizes beta-carotene status of cystic
      fibrosis patients without evidence of significant side effects.

PMID- 8563225
TI  - Factors associated with fatal outcome in childhood meningococcal disease.
AB  - The purpose of this study was to identify factors associated with a fatal outcome
      in children with meningococcal disease and to design a new clinical scoring
      system. We reviewed the charts of all 137 children with meningococcal disease
      admitted alive to the University Hospital, Tromso, during the years 1977-92.
      Twelve of the children died (8.7%). On admission the following clinical signs
      were significantly associated with poor outcome: peripheral vasoconstriction,
      cyanosis, extensive petechiae, hypotension, altered consciousness,
      hyperventilation and absence of neck rigidity. The laboratory parameters low pH,
      low base excess, thrombocytopenia, low Trombotest and leukopenia were also
      associated with later death. Multiple logistic regression was performed to
      examine the independent effect of each variable. Cyanosis, peripheral
      vasoconstriction and base excess < -10 mmol/l or pH < 7.35 were significantly
      associated with a fatal outcome. A clinical scoring system based on the extent of
      petechiae, the presence of peripheral vasoconstriction, hyperventilation and/or
      cyanosis, the absence of neck rigidity and impairment of consciousness is
      proposed. Twenty-nine patients received > or = 3.5 points, of whom 12 died and 12
      survived. None of the patients who died had less than 3.5 points. The clinical
      scoring system is based solely on clinical signs. It can be done rapidly and
      performs well in identifying children who might benefit from early intensive
      care.

PMID- 8563226
TI  - A general hospital population of childhood epilepsy.
AB  - In a general hospital population of 74,000 children under the age of 16 years in
      southern Stockholm, 79 children were started on antiepileptic drugs due to
      epilepsy during the 2 year period 1990-92. The mean annual incidence of childhood
      epilepsy in this area was 53 per 100,000 children younger than 16 years.
      Neurological impairments were identified in 35% of the children. The epilepsy
      diagnoses were set according to the International Classification System proposed
      by the International League Against Epilepsy. Partial seizures were seen in 52%
      of the children. The syndrome BECT was identified in 11%. The epilepsy was
      symptomatic in 30%, and therapy-resistant in 23%.

PMID- 8563227
TI  - Active epilepsy in mentally retarded children. I. Prevalence and additional neuro
      impairments.
AB  - A population-based study of active epilepsy was conducted in 6-13-year-old
      mentally retarded children born between 1975 and 1986. The population at risk
      comprised 48,873 children. Ninety-eight children were identified, 35 mildly and
      63 severely retarded. The prevalence was 2.0 per 1000; 0.7 per 1000 for mildly
      and 1.3 per 1000 for severely retarded children. Sixty-nine children had at least
      one additional neuroimpairment. Cerebral palsy was found in 42 children with a
      majority of spastic/dystonic tetraplegias; visual impairment was present in 24
      and autism in 24. Thirty-three children had only a mild or no gross motor
      disability and mild mental retardation, while 23 had IQs < 20 and a very severe
      gross motor disability. This study underlines the fact that active epilepsy in
      mentally retarded children is often associated with additional neuroimpairments,
      especially a combination of severe cerebral palsy and severe visual impairment.

PMID- 8563228
TI  - Active epilepsy in mentally retarded children. II. Etiology and reduced pre- and
      perinatal optimality.
AB  - A population-based study of active epilepsy in mentally retarded children
      identified 98 children, 6-13 years old. A biopathological origin was established
      in 66% of mildly and 92% of severely retarded children: a prenatal etiology was
      considered in 51% and 57%, a perinatal in 9% and 19%, a postnatal in 6% and 16%
      and an untraceable etiology in 34% and 8%, respectively. Severe mental
      retardation was more frequent in the peri- and postnatal groups (80% and 83%)
      than in the prenatal and untraceable groups (67% and 29%). Thirty-four pre- and
      perinatal optimal items were defined. Children with a prenatal etiology did not
      differ from controls in any of the periods. Children with a perinatal etiology
      had, compared with controls, higher proportions of non-optimal items successively
      increasing through the pre- and perinatal periods showing the accumulation of
      negative events.

PMID- 8563229
TI  - Hearing loss at the age of 5 years of children born preterm--a matter of
      definition.
AB  - The effect of three common hearing impairment criteria on the prevalence of
      hearing loss was evaluated in 58 prospectively followed-up 5-year-old children
      born preterm at < or = 32 weeks of gestation. Audiological assessment was done as
      part of an extensive neurodevelopmental evaluation at the age of 5 years. With
      the criterion based on the classification of the World Health Organization
      (average threshold hearing level > 25 dB at frequencies of 0.5, 1 and 2 kHz,
      classified according to the less impaired side) there were two preterm children
      with mild hearing impairment. With Clark's criterion (unilateral average
      threshold hearing level > 15 dB at frequencies of 0.5, 1 and 2 kHz) eight
      children had slight hearing impairment; seven of these had conductive hearing
      problems. With the criterion of a single frequency-specific deficit > 15 dB for
      0.25-4 kHz the number of hearing-impaired children was 28 out of 54 (51.9%), most
      of whom had conductive or unspecified hearing deficits. Moreover, of the four
      multiply handicapped, retarded children whose pure tone thresholds were not
      assessed monaurally, three would belong to the hearing-impaired group according
      to Clark's criterion and four according to the frequency-specific criterion.

PMID- 8563230
TI  - Parental and primary care physicians' views on the management of chronic
      diseases: a study in Italy. The Italian Collaborative Group on Paediatric Chronic
      Diseases.
AB  - A survey on the burden and quality of care and the parental and primary care
      physicians' views on management of eight chronic illnesses and disabilities was
      conducted from 1990 to 1993. Data were collected on 993 children and adolescents
      from family interviews and physicians' postal questionnaires. Approximately 70%
      of patients used two or more services for care management and 149 children were
      treated outside their region. Only 36% of the physicians were case managers and
      half of these agreed that better communication with other care providers could
      facilitate their role. A wide difference in parental satisfaction was found
      between medical and disabling conditions. Approximately 90% of the parents
      expressed satisfaction with care for children with coeliac disease (112/120),
      asthma (80/89) and diabetes (98/111), whereas approximately one-third of parents
      of children with cerebral palsy and Down's syndrome were dissatisfied (88/242 and
      72/189, respectively). Primary care physicians expressed similar satisfaction
      with case management. Distance from hospital, the need for more information on
      disease management and financial aid were the sources of greatest
      dissatisfaction. Children with disabling diseases had more problems integrating
      at school than children with other chronic disorders. Closer interaction between
      health services, providers and families is necessary to manage the needs of
      disabled (Italian) children better.

PMID- 8563231
TI  - Screening for neuroblastoma: a 9-year birth cohort-based study in Niigata, Japan.
AB  - Between April 1985 and March 1994 (9 years), 229,346 babies were born in Niigata
      prefecture, and 201,888 (88.0%) underwent mass screening (MS) for neuroblastoma
      at 6 months of age. To date, 29 infants have been screen-detected as having
      neuroblastoma (1:7908). All screen-detected patients survived after removal of
      the primary tumor. In the same birth cohort, 17 additional children were
      clinically diagnosed as having neuroblastoma. The cumulative incidence rate of
      neuroblastoma at 5 years of age was 10.5 per 100,000 live births in the 5-year
      birth cohort before MS was introduced, and 18.6 per 100,000 in the first 5-year
      birth cohort after MS was introduced. These values were not statistically
      different. The birth cohort incidence rate increased significantly to 22.2 per
      100,000 (p < 5% compared with before MS) after the method of MS was changed to
      high-power liquid chromatography (HPLC), even though this latest birth cohort has
      not been followed for 5 years. The population-based mortality rate from
      neuroblastoma was 5.9 per 100,000 in the 5-year birth cohort before MS, and 4.5
      per 100,000 after MS in the first 5-year birth cohort, using the vanillymandelic
      acid (VMA) spot test. These values were not statistically significant. In
      contrast, no death was observed in the next 4-year birth cohort after MS using
      HPLC; however, this birth cohort has not yet been followed for 5 years.

PMID- 8563232
TI  - Prediction of complications following unintentional caustic ingestion in
      children. Is endoscopy always necessary?
AB  - The records of 115 children hospitalized following caustic ingestion over an 18.5
      year period from 1976 to 1994 were reviewed. The relationship between types of
      product ingested, signs and symptoms, degree of esophageal injury and
      complications was analyzed. All complications were the result of strong alkali
      ingestion (sensitivity = 1.0). Among the 102 incident patients, 36.8% of lye
      ingestions resulted in complications, whereas only 2.7% (one) of automatic
      dishwasher detergent (ADD) ingestions caused any complications (p < 0.01).
      Endoscopy 6 h to 4 days after injury was accurate in predicting or identifying
      complications in all types of strong alkali ingestions. In lye ingestions,
      endoscopy was not superior to the test, "one or more signs or symptoms" in
      predicting complications (predictivity = 1.0). Endoscopy is recommended to
      establish or confirm a prognosis, or to identify acute respiratory complications,
      in symptomatic ingestions of lye or ammonia water, in children with respiratory
      symptoms, and in rare cases of severe symptoms following ADD or strong acid
      ingestion. It is suggested that children who are non-symptomatic following
      unintentional ingestions are not at risk of complications and do not need
      endoscopic examination.

PMID- 8563233
TI  - Creatine kinase isoenzyme BB concentrations in cerebrospinal fluid in asphyxiated
      preterm neonates.
AB  - Creatine kinase isoenzyme BB was determined in cerebrospinal fluid (CSF) in 79
      preterm neonates using an original enzyme-linked immunosorbent assay. The
      criterion for inclusion was an Apgar score of 7 or less at 5 min of life.
      Neurological examination was performed on day 2 and day 5 of life. CSF was
      obtained on the same days. Lumbar puncture was performed on 41 of these babies on
      day 2 and in 39 on day 5 of life (one baby underwent lumbar puncture twice). All
      babies had clinical features of hypoxic-ischemic encephalopathy (HIF) which was
      classified according to Sarnat and Sarnat. The control group consisted of 90
      asphyxiated term babies and 30 adults without CNS pathology. The concentration of
      CK-BB in cerebrospinal fluid (mean +/- SD) was significantly higher (p < 0.0005)
      in preterm (168.0 +/- 2) than in term babies (29.0 +/- 3.1) and healthy adults
      (5.3 +/- 1.2). Our results demonstrate the possibility of using the
      classification system of Sarnat and Sarnat for assessment of the severity of
      brain damage not only in term, but also in preterm babies. Neonates with HIE
      stages II and III showed markedly higher CK-BB values than those with HIE I on
      day 2 (p < 0.025) and day 5 (p < 0.05) of life. CK-BB values were markedly higher
      in preterm babies with none of some primitive responses (head turning, Babkin's
      reflex, palmar grasp). The mean concentration of CK-BB was higher in neonates
      with retarded psychomotor development compared with those with normal development
      (p < 0.05) on day 3, and after 6 and 9 months. At 12 months of age no significant
      difference in median CK-BB concentration was detected between neonates with
      normal and developmental disturbances.

PMID- 8563234
TI  - Inhaled nitric oxide in infants with developing or established chronic lung
      disease.
AB  - The effect on gas exchange of increasing concentrations of nitric oxide (0-60
      parts per million) added to the inspired gases of nine ventilator-dependent
      infants (median postnatal age = 4 weeks; range 2-16 weeks) with chronic lung
      disease and pathological oxygenation index values was studied by means of
      arterial or transcutaneous PO2/PCO2. A significant improvement of oxygenation,
      indicated by a reduction of oxygenation index, was found (p < 0.014). The optimal
      nitric oxide concentration and the individual response varied between patients.
      PO2 returned to baseline values after the discontinuation of nitric oxide in all
      patients except one. No effect on PCO2 could be identified. Methaemoglobin values
      only increased marginally during the nitrous oxide exposition (pre-nitric oxide:
      0.56% +/- 0.27; post-nitric oxide: 0.78 +/- 0.08; p = ns). Systemic blood
      pressure and heart rate were unaffected in all patients. Before inhaled nitric
      oxide can be considered for prolonged use in this patient category further
      studies regarding long-term efficacy and safety are needed.

PMID- 8563235
TI  - Rapidly progressive enlargement of the fourth ventricle in the preterm infant
      with post-haemorrhagic ventricular dilatation.
AB  - Six preterm infants who developed disproportionate enlargement of the 4th
      ventricle during the neonatal period, associated with post-haemorrhagic
      ventricular dilatation (PHVD), before shunt placement are reported. Five of the
      six preterm infants developed cyanotic spells and/or bradycardias at the time of
      rapid enlargement of the 4th ventricle, suggestive of raised posterior fossa
      pressure, which resolved following insertion of and drainage from a subcutaneous
      reservoir. In one of the three survivors an isolated 4th ventricle was
      subsequently diagnosed later in infancy, requiring drainage. These data suggest
      that a combination of an enlarged 4th ventricle on ultrasound and cyanotic spells
      and/or bradycardias should lead to rapid release of raised pressure in the
      posterior fossa. Long-term follow-up of these children is necessary, as isolation
      of the 4th ventricle can subsequently develop.

PMID- 8563236
TI  - Onset mortality of type I diabetes in 0 to 19-year-old children in The
      Netherlands, 1988-1990.

PMID- 8563237
TI  - Cystic fibrosis caused by homozygosity for the CFTR gene mutation 175insT.

PMID- 8563238
TI  - Congenital hypopituitarism with hypoplasia of the anterior pituitary gland and a
      normal posterior pituitary lobe.
AB  - We report a female infant with congenital hypopituitarism. All anterior pituitary
      hormones were deficient, and the anterior pituitary gland was undetectable on
      magnetic resonance images. Antidiuretic hormone secretion was appropriate, and
      the posterior lobe was localized at the end of the stalk, in the sella. These
      observations suggest that the posterior pituitary gland may develop independently
      of the anterior lobe.

PMID- 8563239
TI  - Assessment of iron status in infants.

PMID- 8563240
TI  - Interleukin-2 therapy of Langerhans cell histiocytosis.
AB  - A 20-month-old girl was diagnosed with Langerhans cell histiocytosis on the basis
      of a seborrheic skin rash, multiple punched out bony lesions, and skin biopsy
      findings. Combination therapy including alpha-interferon, vincristine, vindesine,
      cyclophosphamide, etoposide, cisplatin, betamethasone, THP-adriamycin, cytarabine
      and methotrexate was ineffective. Because cyclophosphamide enhanced lesion growth
      within the skull, we administered an intravenous infusion of interleukin-2 with
      remarkable efficacy. The reduction in lesion size with interleukin-2 treatment
      paralleled the increase in the percentage of CD16-positive natural killer cells
      in the peripheral blood.

PMID- 8563241
TI  - Growth promotion by oxandrolone in a girl with short stature and early pubertal
      development treated with growth hormone and gonadotropin-releasing hormone
      analogue. A case study.
AB  - Gonadotropin-releasing hormone (GnRH)-analogues are widely used for treating
      precocious puberty, and occasionally in short patients and patients with growth
      hormone deficiency, in order to delay pubertal development and increase final
      height. Yet, many of these children only decelerate growth velocity and neither
      improve in final height nor even in height prediction. As GnRH-analogue treatment
      dramatically reduces sexual steroid levels, I hypothesized the need for steroid
      hormone substitution during this treatment. Growth promotion was tried in a
      healthy girl, with a very unsatisfying height prediction of only 144 cm, using a
      combination of GnRH-analogue (75 micrograms/kg/4 weeks), plus growth hormone (4
      IU/m2/d), plus oxandrolone (1 mg/d). Knemometric measurements of lower leg growth
      velocity demonstrated that GnRH-analogue alone depresses growth. Additional GH
      administration only sporadically increases growth velocity, and not until the
      additional substitution of oxandrolone does growth velocity catch up and return
      to near pretreatment level. In spite of a 10.3 cm increase in body height during
      the 15-month period of observation, little bone age progression took place, and
      height prediction improved from 144 cm to over 149 cm after 9 months, and to 152
      cm after 15 months of observation.

PMID- 8563242
TI  - Aminophylline versus caffeine citrate...

PMID- 8563243
TI  - The newborn should be protected from dangerous transient induced hypothyroidism.

PMID- 8563244
TI  - Pathogenicity of Moraxella catarrhalis in cystic fibrosis.

PMID- 8563245
TI  - The bioethics discussion forum--an implementation of an Internet-based bioethics
      information analysis resource.
AB  - Ethical analysis is crucial to decision making in biomedicine and health care,
      necessitating both rapid access to diffusely disseminated sources of information
      pertinent to bioethics and promotion of analysis in the field of bioethics
      through a resource for information analysis. We developed the Bioethics
      Discussion Forum, an Internet-based information analysis resource, in order to
      supplement the Bioethics Online Service with an interactive information medium to
      meet the demand for such an interactive resource. The Bioethics Discussion Forum
      has shown promise for information analysis, providing an arena for the review and
      discussion of complex bioethical information, establishing a connection
      nationally and internationally among individuals with high levels of expertise in
      bioethics, and providing a template for future interactive informatics services.

PMID- 8563246
TI  - Developing AJN Network: phase two. An information resource for nurses.
AB  - In September of 1993 the American Journal of Nursing Company was awarded a three
      year Special Projects Grant from the Division of Nursing, Department of Health
      and Human Services to develop a national information service that would provide a
      variety of formal and informal continuing education services to nurses in
      medically underserved communities. AJN Network went "live" in March 1994 and our
      progress in our first year of operation was presented at SCAMC in 1994. During
      the first year of operation, AJN Network was available through a dial in service.
      In September 1994 we became an Internet node. This presentation will detail our
      progress in Year 2 of the grant period, describing expansion of user base and
      content, new content offerings, initial stages of WEB development and plans for
      future development.

PMID- 8563247
TI  - The informatics superhighway: prototyping on the World Wide Web.
AB  - We have experimented with developing a prototype Surgeon's Workstation which
      makes use of the World Wide Web client-server architecture. Although originally
      intended merely as a means for obtaining user feedback for use in designing a
      "real" system, the application has been adopted for use by our Department of
      Surgery. As they begin to use the application, they have suggested changes and we
      have responded. This paper illustrates some of the advantages we have found for
      prototyping with Web-based applications, including security aspects.

PMID- 8563248
TI  - WHAM!: a forms constructor for medical record access via the World Wide Web.
AB  - WWW-EMRS is an architecture that provides a set of abstractions of electronic
      medical record systems (EMRS). This architecture has enabled us to implement
      interfaces to heterogeneous EMRS via the World-Wide Web that provide consistent
      visual presentations and functionality. We describe WHAM!, a program that allows
      rapid generation of customized interfaces to WWW-EMRS that therefore deliver the
      customized functions across multiple EMRS.

PMID- 8563249
TI  - An overview of the CERC ARTEMIS project.
AB  - The basic premise of this effort is that health care can be made more effective
      and affordable by applying modern computer technology to improve collaboration
      among diverse and distributed health care providers. Information sharing,
      communication, and coordination are basic elements of any collaborative endeavor.
      In the health care domain, collaboration is characterized by cooperative
      activities by health care providers to deliver total and real-time care for their
      patients. Communication between providers and managed access to distributed
      patient records should enable health care providers to make informed decisions
      about their patients in a timely manner. With an effective medical information
      infrastructure in place, a patient will be able to visit any health care provider
      with access to the network, and the provider will be able to use relevant
      information from even the last episode of care in the patient record. Such a
      patient-centered perspective is in keeping with the real mission of health care
      providers. Today, an easy-to-use, integrated health care network is not in place
      in any community, even though current technology makes such a network possible.
      Large health care systems have deployed partial and disparate systems that
      address different elements of collaboration. But these islands of automation have
      not been integrated to facilitate cooperation among health care providers in
      large communities or nationally. CERC and its team members at Valley Health
      Systems, Inc., St. Marys Hospital and Cabell Huntington Hospital form a
      consortium committed to improving collaboration among the diverse and distributed
      providers in the health care arena. As the first contract recipient of the multi
      agency High Performance Computing and Communications (HPCC) Initiative, this team
      of computer system developers, practicing rural physicians, community care
      groups, health care researchers, and tertiary care providers are using research
      prototypes and commercial off-the-shelf technologies to develop an open
      collaboration environment for the health care domain. This environment is called
      ARTEMIS--Advanced Research TEstbed for Medical InformaticS.

PMID- 8563250
TI  - LabTalk/2: a middleware approach to HIS integration.
AB  - LabTalk/2 is an intelligent interface between a legacy order-entry system and a
      legacy laboratory information system. Unlike other interfaces, LabTalk/2 does
      more than just transform data from one format to another; it transforms the
      manner in which data is processed. Utilizing the "middleware" concept, it sits
      independently between the two systems, decoupling their maintenance needs.
      Implementation has been successful.

PMID- 8563251
TI  - An efficient delivery of historical information for the Mendelian Inheritance in
      Man database.
AB  - The ability to manage information with regard to changes in a database is
      critical for quality control. This information can also provide audit trails
      about the time of the change and the person who made the change. In addition,
      historical information can provide the proper context in which to interpret the
      relationships between the current and past data. In most genomic databases, only
      the most recent copy of the information is presented to the user, thereby losing
      the audit trail and the historical context. Therefore, we have constructed a
      delivery mechanism for the historical information in the Mendelian Inheritance in
      Man database. Furthermore, this feature was designed to optionally display only
      the changes so that the user can bypass the unchanged portions of the text. It
      was anticipated that technical problems would influence the acceptance of this
      information delivery. However, the involvement of the editorial staff became the
      critical factor.

PMID- 8563252
TI  - Legacy systems: managing evolution through integration in a distributed and
      object-oriented computing environment.
AB  - Legacy systems are crucial for organizations since they support key
      functionalities. But they become obsolete with aging and the apparition of new
      techniques. Managing their evolution is a key issue in software engineering. This
      paper presents a strategy that has been developed at Broussais University
      Hospital in Paris to make a legacy system devoted to the management of health
      care units evolve towards a new up-to-date software. A two-phase evolution
      pathway is described. The first phase consists in separating the interface from
      the data storage and application control and in using a communication channel
      between the individualized components. The second phase proposes to use an object
      oriented DBMS in place of the homegrown system. An application example for the
      management of hypertensive patients is described.

PMID- 8563253
TI  - Representing hospital events as complex conditionals.
AB  - We have developed an approach to medical knowledge representation whereby simple
      medical concepts are combined to yield complex statements of testable medical
      logic. The logic is created from a small number of generic medical concepts that
      are instantiated and combined to create the rules. Rule writing is done through a
      rule editor and requires knowledge of the system's data dictionaries, though no
      programming is required. We have used the approach to create a large knowledge
      base including panic lab alerting rules, drug-laboratory interaction alerting
      rules, an adverse drug event monitor, and a drug-age interaction detection
      program. The rules have been used as part of an alerting system and for data
      collection to determine the frequency of events of interest. The scheme is
      extensible and yields a readable form of the created knowledge. The scheme holds
      great promise as a durable form of medical knowledge representation.

PMID- 8563254
TI  - ASOP: a new method and tools for capturing a clinical encounter.
AB  - ASOP is a proposed method for future medical record notation. This permutation of
      the original POMR-SOAP method is necessary to provide the standardized workflow
      and medical nomenclature which will be essential for automated medical record
      systems and forms-based encounter recording. The development of an ASOP system is
      dependent on tools to map assessment to appropriate terminology within a
      universal medical dictionary and generate intelligent queries across the World
      Wide-Web. In this study we intend to demonstrate the need for change in the POMR
      system and highlight some of the current tools in development to make the ASOP
      method the medical record notation system of choice.

PMID- 8563255
TI  - Patient entries in the electronic medical record: an interactive interview used
      in primary care.
AB  - We describe the development, implementation, and use of a computer-administered
      patient interview, the Health History Interview, by over 300 new patients in a
      primary care practice at Boston's Beth Israel Hospital. The interview has been
      well accepted by patients and rated positively by providers. It electronically
      captures clinical information directly from patients for use during their initial
      encounter with a provider. It facilitates aggregate analysis of clinical data for
      quality improvement efforts, such as aiming preventive medicine interventions at
      identified problem areas within the clinic. Expectations management has been an
      important task throughout the project. Increasing use of the interview beyond the
      30-40% of new patients who have taken it will require greater communication with
      patients, greater convenience to patients and providers, and more evidence of the
      clinical, administrative, and research benefits of the technique. Most important,
      full implementation will require fundamental changes in physician practice habits
      and patterns of communication between patients and the health care system, as
      well as clearly demonstrated cost-benefit improvements through the use of these
      tools.

PMID- 8563257
TI  - Implementing an EMR: paper's last hurrah.
AB  - The implementation of an electronic medical record system in any large
      organization is as complex a task as the design of the system. During
      implementation, it is necessary that health care providers using the electronic
      system are able to communicate with colleagues who are continuing to work with
      the paper record. The Mayo Clinic in Rochester, Minnesota, is well along the path
      to implementing an electronic medical record system. One of the key issues
      addressed has been the need for the electronic system to integrate with the paper
      record. This need to function in the dual electronic/paper environment has placed
      new demands on printers, required revision of some paper forms, and required the
      electronic system to create facsimilies of paper record forms. In addition, new
      security issues have been raised. Dual paper/electronic environment issues are an
      important challenge in the implementation of an electronic medical record.

PMID- 8563256
TI  - Enroute toward a computer based patient record: the ACIS project.
AB  - The clinical arm of the University of Utah operates a 400 bed general hospital
      and 30 specialty and subspecialty clinics and with the advent of managed care
      will soon be linked to a much wider network of health care facilities throughout
      the state. Each of these patient care facilities maintains its own patient
      record. To provide common access to data on any patient needed to provide
      continuity to the care process where ever it occurs, the institution has embarked
      on the development of a completely electronic patient record. In this paper we
      will describe the route we have taken to achieve this goal in hopes of providing
      some sign posts along the way for others seeking the same destination.

PMID- 8563258
TI  - Nurses, pagers, and patient-specific criteria: three keys to improved critical
      value reporting.
AB  - At LDS Hospital, we have developed and evaluated a computerized critical value
      reporting system based on digital pagers. Criteria used to identify critical
      values are patient-specific. An evaluation of the system was conducted from
      October 23, 1993 to January 21, 1994. Results showed that 100% of all critical
      values (497 values in the form of 335 alerts) were reported to clinicians within
      an average of 38.6 minutes, and that 51% of all alerts were received within 12
      minutes. Data also showed that 92% of the alerts were considered valid, that 76%
      were communicated directly to the primary care nurse, and that 67% of the time
      nurses were previously unaware of the critical value(s).

PMID- 8563259
TI  - Medical decision support: experience with implementing the Arden Syntax at the
      Columbia-Presbyterian Medical Center.
AB  - We began implementation of a medical decision support system (MDSS) at the
      Columbia-Presbyterian Medical Center (CPMC) using the Arden Syntax in 1992. The
      Clinical Event Monitor which executes the Medical Logic Modules (MLMs) runs on a
      mainframe computer. Data are stored in a relational database and accessed via
      PL/I programs known as Data Access Modules (DAMs). Currently we have 18 clinical,
      12 research and 10 administrative MLMs. On average, the clinical MLMs generate
      50357 simple interpretations of laboratory data and 1080 alerts each month. The
      number of alerts actually read varies by subject of the MLM from 32.4% to 73.5%.
      Most simple interpretations are not read at all. A significant problem of MLMs is
      maintenance, and changes in laboratory testing and message output can impair MLM
      execution significantly. We are now using relational database technology and
      coded MLM output to study the process outcome of our MDSS.

PMID- 8563260
TI  - Automated patient care documentation: what's in it for us? An expert system
      emergency drug card printout.
AB  - This article summarizes experiences to date for a collaborative approach,
      utilizing systems analysis and decision support methods, to design, develop, and
      implement automated patient centered documentation. Current manual methods for
      retrieving patient centered data for treatment activities and evaluation of
      practice are laborious, frustrating and often uneventful. Accessing specific
      patient information in an arrest or emergent situation, in the hospital and out
      patient clinical setting, is fraught with difficulties of data and information
      availability, reliability, legibility, integrity, security, and obsolescence.
      Treatment decisions made during an arrest or emergent situation, whether for an
      in-patient or clinical out patient, utilize Advanced Life Support guidelines and
      also may vary based on the heuristics of the lead practitioner on duty at the
      time. Walking the informatics talk of "managing and processing data to
      information to knowledge" lead to standardization for best practice of emergency
      drug calculations and treatments (1). An expedient and reliable method for
      retrieving patient specific data to calculate 26 medications, 3 treatments, and
      upwards of 40 criteria to consider during an arrest or emergent situation was
      achieved and implemented, as a by product of height and weight charting, across
      most all patient care areas at Primary Children's Medical Center in Salt Lake
      City Utah.

PMID- 8563261
TI  - Real-time wireless decision support alerts on a Palmtop PDA.
AB  - The authors devised a system which continuously analyzes data exported from a
      Clinical Information System for the occurrence of exceptional or life-threatening
      clinical events. A configurable rule-based system was created to detect and act
      on such events. When detected, the system formats an alerting message, dials a
      modem and transmits the message to a commercial satellite relay system.
      Ennunciated by an alerting beep and blinking LED on a PCMCIA receiver card, the
      alert message appears on the screen of a Palmtop Personal Digital Assistants
      (PDA) carried by designated clinicians.

PMID- 8563262
TI  - A tool for provider interaction during patient care: G-CARE.
AB  - We have extended the CARE language to facilitate interaction with providers using
      the Medical Gopher order entry system during patient care to create G-CARE. We
      have used G-CARE in several randomized controlled trials and for routine clinical
      applications. The language has evolved and is now able to support nearly all of
      the decision support. Its flexibility allows G-CARE results to be used at many
      points throughout the patient care process. Based on actual use of G-CARE, we
      have found performance issues and lack of dynamically grouped order sets are
      limitations which need to be addressed.

PMID- 8563263
TI  - The Single Logon Application: an enabler for access to disparate systems in a
      patient-focused care environment.
AB  - The presence of separate, independent systems for patient results is a common
      problem in many institutions. The Single Logon Application (SLA) was developed to
      mitigate the problems presented by these disparate systems, and its use was a key
      component in a Patient-Focused Care (PFC) implementation.

PMID- 8563264
TI  - Verification & validation algorithms for data used in critical care decision
      support systems.
AB  - A decision support system is only as good as the data generating that decision
      support system. If the data is incorrect, doesn't relate to the other pieces of
      data, is missing or is not consistent, the decision support system conclusions
      may be incorrect and inconsistent. While collecting data from several sites
      during a multicenter randomized clinical trial, we found that some critical data
      elements were missing, out of correct ranges, totally illogical, and/or
      inconsistently recorded. In order to get consistent, correct, and dependable
      information from a our decision support system, the data elements used in that
      system had to be checked for completeness, valid values, consistent units of
      measurement, and relationships to other items. Development of data quality
      assurance rules and the application of those rules is imperative to using the
      data to generate daily scores for multiple organ failure, sepsis, and barotrauma.

PMID- 8563265
TI  - Analysis of medical decision making: a cognitive perspective on medical
      informatics.
AB  - The improved support of complex medical decision making will require a greater
      understanding of the cognitive processes of physicians. Decision making in
      medicine often involves the careful weighing of uncertain and ill-structured
      information from various sources. In this paper a cognitive approach to analyzing
      complex intensive care decision making is outlined. The study described involved
      the presentation of case descriptions of systematically varied complexity, to two
      levels of physicians: intensive care residents (intermediates) and intensive care
      specialists (experts). Subjects were asked to "think aloud" in providing
      treatment and management decisions for the cases. The audiotaped protocols were
      then analyzed for the use of decision strategies and for key aspects of decision
      making. It was found that expert subjects tended to focus on developing a more
      refined situational analysis of the decision problem. The study results are being
      used in the design of a system for aiding physicians in making complex decisions
      in intensive care medicine.

PMID- 8563266
TI  - Concept formation vs. logistic regression: predicting death in trauma patients.
AB  - This paper discusses two classification models, one based on concept formation
      and the other using standard logistic regression. The models are first explained
      in some detail and then evaluated on the same population of trauma patients. The
      goal of both systems is to predict the outcome of those patients. The results are
      summarized and explained in terms of differing algorithms of the two models.

PMID- 8563267
TI  - Support for information management in critical care: a new approach to identify
      needs.
AB  - Managing information is necessary to support clinical decision making and action
      in critical care. By understanding the nature of information management and its
      relationship to sound clinical practice, we should come to use technology more
      wisely. We demonstrated that a new approach inspired by ethnographic research
      methods could identify useful and unexpected findings about clinical information
      management. In this approach, a clinician experienced in a specific domain
      (critical care), with advice from a medical anthropologist, made short-term
      observations of information management in that domain. We identified 8 areas in a
      critical care Unit in which information management was seriously in need of
      better support. We also found interesting differences in how these needs were
      viewed by nurses and physicians. Our interest in this approach was at two levels:
      1. Identify and describe representative instances of sub-optimal information
      management in a critical care Unit. 2. Investigate the effectiveness of such
      short-term observations by clinicians. Our long-range goal is to explore the use
      of this approach and the information it reveals to optimize the process of
      developing and selecting new information support tools, preparing for their
      introduction, and optimizing clinical outcomes.

PMID- 8563268
TI  - Clinical simulation using context-sensitive temporal probability models.
AB  - We present a language for representing context-sensitive temporal probabilistic
      knowledge. Context constraints allow inference to be focused on only the relevant
      portions of the probabilistic knowledge. We provide a declarative semantics for
      our language and an implemented algorithm (BNG) that generates Bayesian networks
      to compute the posterior probabilities of queries. We illustrate the use of the
      BNG system by applying it to the problem of modeling the effects of medications
      and other interventions on the condition of a patient in cardiac arrest.

PMID- 8563269
TI  - Preliminary investigation of a Bayesian network for mammographic diagnosis of
      breast cancer.
AB  - Bayesian networks use the techniques of probability theory to reason under
      conditions of uncertainty. We investigated the use of Bayesian networks for
      radiological decision support. A Bayesian network for the interpretation of
      mammograms (MammoNet) was developed based on five patient-history features, two
      physical findings, and 15 mammographic features extracted by experienced
      radiologists. Conditional-probability data, such as sensitivity and specificity,
      were derived from peer-reviewed journal articles and from expert opinion. In
      testing with a set of 77 cases from a mammography atlas and a clinical teaching
      file, MammoNet performed well in distinguishing between benign and malignant
      lesions, and yielded a value of 0.881 (+/- 0.045) for the area under the receiver
      operating characteristic curve. We conclude that Bayesian networks provide a
      potentially useful tool for mammographic decision support.

PMID- 8563270
TI  - A new formalism for temporal modeling in medical decision-support systems.
AB  - We present a new mathematical formalism, which we call modifiable temporal belief
      networks (MTBNs) that extends the concept of an ordinary belief network (BN) to
      incorporate a dynamic causal structure and explicit temporal semantics. An
      important feature of MTBNs is that they allow portions of the model to be
      abstract and portions of it to be temporally explicit. We show how this property
      can lead to substantial knowledge acquisition and computational complexity
      savings. In addition to temporal modeling, the language of MTBNs can be an
      important analytical tool, as well as temporal language for causal discovery.

PMID- 8563271
TI  - Using belief networks to enhance sharing of medical knowledge between sites with
      variations in data accuracy.
AB  - Differences in data definition between sites are a known obstacle to sharing of
      reminder-system rule sets. We identify another data characteristic--data accuracy
      -with implications for sharing. We reviewed the literature on data accuracy and
      found reports of high error rates for many data classes used by reminder systems
      (e.g., problem lists). The accuracy of other, equally important, data classes had
      not been characterized. Wide variations in accuracy between sites has been
      observed, suggesting that such differences may pose a previously unrecognized
      barrier to sharing of reminder rules. We propose a belief-network model for
      encoding reminder rules that explicitly models site-specific data accuracy and we
      discuss how encoding knowledge in this format may lower the cost and effort
      required to share reminder rules between sites.

PMID- 8563272
TI  - CareBase: a reference base for nursing.
AB  - Due to the lack of generally accepted nursing classifications and standards in
      Germany the introduction of nursing information systems for planning and
      documentation of care is a very time consuming process since the classifications
      and standards must be defined locally to adjust the systems. At the University
      Hospital Freiburg a nursing reference system was developed to collect this
      knowledge, make it available for easy reference and as a source usable for the
      initialisation of nursing information systems to be installed in the future.

PMID- 8563273
TI  - Representation of clinical practice guidelines through an interactive World-Wide
      Web interface.
AB  - The widespread utility of clinical practice guidelines is greatly dependent on
      the ease with which they can be accessed, used, and applied. Because it supports
      hyperlinking and is widely accessible, the World-Wide Web is a medium that is
      well suited for browsing through guidelines. We have developed a process for
      implementing algorithmic guidelines into a graphical format that allows the user
      to browse these guidelines in an interactive fashion. The guidelines we used were
      already in or could be transformed to an algorithmic format that lends itself
      well to analysis with decision table techniques, which in turn permits a fairly
      straightforward conversion into a graphical representation. The results of this
      process allow a user to browse a particular guideline algorithm and to visualize
      the traversed parts of the algorithm by flowcharts. Our first experiences with
      this method of representing a few sample clinical practice guidelines have been
      encouraging, and we hope to extend this method to other guidelines.

PMID- 8563274
TI  - Computerized practice guidelines for heart failure management: the HeartMan
      system.
AB  - In this paper we discuss the initial stages of development and evaluation of the
      HeartMan system, a set of computerized practice guidelines for heart failure
      management. The concept of computerized guidelines as a hybrid of expert systems
      and practice guidelines methodologies and techniques is proposed. We show the
      results of the initial evaluation of the system, which are very promising,
      although the sample size is small, and the study is retrospective: Of 177
      messages, 90% were considered appropriate, of which 97.5% would have been
      followed. Eight percent of the messages were classified as neutral, and 2%
      classified as inappropriate. The errors were correctable by changing the logic.
      The potential technical and sociological barriers to the complete development and
      clinical use of the system are discussed.

PMID- 8563275
TI  - An architecture for a distributed guideline server.
AB  - A number of barriers exist which prevent the widespread integration of practice
      guidelines with electronic medical record systems. These include dependencies on
      clinical databases, as well as problems with converting existing guideline
      specifications into computable rules. We are developing the MBTA (Modeling Better
      Treatment Advice) practice guideline system which uses a distributed client
      server architecture and an object-oriented data representation to support
      practice guidelines usable by different electronic medical record systems. We
      describe the structure and organization of MBTA, focusing on how an open systems
      design, combined with principles of guideline implementation, can be used to
      provide a general purpose guideline server for use by a variety of clinical
      workstations.

PMID- 8563276
TI  - Using intermediate states to improve the ability of the Arden Syntax to implement
      care plans and reuse knowledge.
AB  - The Arden Syntax is one of a few knowledge representation languages currently in
      use for clinical decision support. While some of these languages are being used
      in active patient care settings, none have gained widespread acceptance as a
      clinical tool. Prior attempts to represent temporally complex care plans in the
      Arden Syntax have revealed difficulties in representing and tracking series of
      consecutive time-oriented events and recommendations, in sharing and reusing
      knowledge and in dealing with unobtainable data. In an attempt to improve Arden's
      ability to deal with these problems and demonstrate the importance of these
      factors, the clinical event monitor has been adapted to store coded data
      representing Intermediate States in the Columbia Presbyterian Medical Center
      (CPMC) central data repository. The Intermediate States define the current state
      of the patient as laid out in the care plan. Four care plans were constructed.
      The findings include an improved ability to track complex series of events and
      recommendations over long periods of time. The knowledge generated by the
      electronic care plans was able to be reused by the care plan that generated it,
      by other elements of the knowledge base and by non-decision support applications.
      Modular development, facilitated by the changes, simplified dealing with data not
      available to the central data repository by aiding the implementation of those
      parts of the care plan for which sufficient data is available.

PMID- 8563277
TI  - Medical informatics academia and industry: a symbiotic relationship that may
      assure survival of both through health care reform.
AB  - There are often clear lines drawn identifying the demilitarized zone between
      medical informatics academics and industry. Academics were "pure" intellectuals
      sequestered in ivory towers that effectively shielded them from the realities of
      the world. Industry has historically focused on creating effective products that
      produce financial return to the corporation. Both the paradigms of academia and
      industry are quickly becoming dinosaurs in the era of health care reform where
      both medical informatics academia and industry are under increasing pressure to
      develop and prove that medical informatics has a positive impact on health care
      both in terms of the quality of care as well as cost. Unfortunately, neither
      academia or industry alone are going to be able to successfully complete this
      task. The purpose of this paper is to describe such a collaborative effort that
      has produced a computerized decision support system for the management of
      mechanical ventilation in patients with the Adult Respiratory Distress Syndrome
      (ARDS) that is now installed and supported on three different commercial CIS
      platforms. This collaborative effort has allowed us to successfully mount a large
      multi-center clinical trial designed to determine efficacy.

PMID- 8563278
TI  - A successful protocol for the use of pulse oximetry to classify arterial
      oxygenation into four fuzzy categories.
AB  - Pulse oximetry is widely used in critical care medicine to noninvasively estimate
      arterial hemoglobin oxygen saturation. Despite the obvious benefits of using
      pulse oximetry to detect life threatening desaturations, it is unknown how well
      pulse oximetry is able to predict the finer graduations of arterial oxygenation
      needed for clinical decision making. A computerized protocol was developed for
      the use of pulse oximetry to classify arterial oxygenation into four fuzzy
      categories and tested in a prospective clinical trial which compared the
      oxygenation category assigned by the protocol to one assigned by a respiratory
      therapist. In 3,742 classifications from 15 patients over a seven month period,
      the protocol showed 96% agreement with the therapists in the direction of therapy
      and 75% agreement with the oxygenation classes assigned by the therapists.

PMID- 8563279
TI  - Formalisation of safety reasoning in protocols and hazard regulations.
AB  - Written protocols are often employed to guide patient care. For treatment within
      a clinical trial, compliance with the trial protocol may be critical in ensuring
      efficacy and safety. Previous empirical work has established generic safety
      principles for reasoning about adverse events in clinical trials and their
      formalisation has been applied in a decision support system for managing
      treatment plans in oncology. The same generic knowledge can be reused to generate
      specific safety clauses when designing new treatment plans. Typically, clinicians
      devise trial protocols relatively infrequently and so software aids, especially
      those assisting with regulatory/safety conformance, will encourage more effective
      use of their time. A similar approach to the formalisation of safety knowledge in
      the control of hazardous industrial processes is discussed.

PMID- 8563280
TI  - Prevention of sudden cardiac death: a probabilistic model for decision support.
AB  - As part of the Cardiac Arrhythmia and Risk of Death Patient Outcomes Research
      Team (CARD PORT) study we are developing a comprehensive decision model to help
      physicians identify preferred strategies for preventing sudden cardiac death. The
      model integrates three components: a screening model, a treatment model, and a
      value model. Ultimately this model will use the CARD PORT's collective findings
      to produce policy recommendations and will support patient-specific clinical
      decision making. Our initial modeling suggests the importance of patient-specific
      value models in an analysis of treatment options. Although our model is specific
      to cardiac sudden death, other medical domains that exhibit similar
      characteristics--the importance of patient preferences and the uncertainty
      regarding the benefits of strategies for risk stratification and treatment--can
      use a conceptual framework similar to the approach we used to represent
      strategies to prevent sudden cardiac death.

PMID- 8563281
TI  - Using knowledge maintenance for preference assessment.
AB  - Most real-life decisions require the decision maker to make trade-offs in order
      to fulfill multiple conflicting objectives. This is especially true in medical
      decision making while selecting the optimal therapy plan from among competing
      therapy plans for a patient. Multi-attribute utility theory provides a framework
      to specify these trade-offs for optimal decision making based on the preferences
      of the decision maker. However traditional preference-assessment techniques are
      difficult to implement and rarely elicit the true preferences of the decision
      maker. We describe a new preference-assessment method based on the concept of
      knowledge maintenance where the preference model is changed each time it makes an
      incorrect recommendation. The method is implemented in a decision-theoretic
      system to evaluate competing three-dimensional radiation treatment plans. The
      preference-assessment method leads to preference models which perform better than
      preference models elicited using traditional assessment techniques.

PMID- 8563282
TI  - Analysis of medical texts based on a sound medical model.
AB  - Automatic understanding of natural language is a complex task due to the presence
      of ambiguities. In particular, semantic ambiguities which are often immediately
      and unconsciously solved by human beings, are raised when analyzing natural
      language sentences by computer. The latter has to know the implicit and
      contextual information in order to resolve these difficulties. Nowadays in
      medicine, a considerable effort is deployed to model semantic contents of the
      medical domain. Such a task is usually performed separately from linguistic
      considerations. The goal of this paper is to highlight the key issues of basing a
      medical language processing system on a sound semantic model. To illustrate the
      requirements and advantages of such a conceptual approach to the analysis
      process, the experiment conducted to adjust the RECIT analyzer to the GALEN model
      is shown.

PMID- 8563283
TI  - Knowledge discovery in clinical databases based on variable precision rough set
      model.
AB  - Since a large amount of clinical data are being stored electronically, discovery
      of knowledge from such clinical databases is one of the important growing
      research area in medical informatics. For this purpose, we develop KDD-R (a
      system for Knowledge Discovery in Databases using Rough sets), an experimental
      system for knowledge discovery and machine learning research using variable
      precision rough sets (VPRS) model, which is an extension of original rough set
      model. This system works in the following steps. First, it preprocesses databases
      and translates continuous data into discretized ones. Second, KDD-R checks
      dependencies between attributes and reduces spurious data. Third, the system
      computes rules from reduced databases. Finally, fourth, it evaluates decision
      making. For evaluation, this system is applied to a clinical database of
      meningoencephalitis, whose computational results show that several new findings
      are obtained.

PMID- 8563284
TI  - A web-based architecture for a medical vocabulary server.
AB  - For health care providers to share computing resources and medical application
      programs across different sites, those applications must share a common medical
      vocabulary. To construct a common vocabulary, researchers must have an
      architecture that supports collaborative, networked development. In this paper,
      we present a web-based server architecture for the collaborative development of a
      medical vocabulary: a system that provides network services in support of medical
      applications that need a common, controlled medical terminology. The server
      supports vocabulary browsing and editing and can respond to direct programmatic
      queries about vocabulary terms. We have tested the programmatic query-response
      capability of the vocabulary server with a medical application that determines
      when patients who have HIV infection may be eligible for certain clinical trials.
      Our emphasis in this paper is not on the content of the vocabulary, but rather on
      the communication protocol and the tools that enable collaborative improvement of
      the vocabulary by any network-connected user.

PMID- 8563285
TI  - An object-oriented, knowledge-based system for cardiovascular rehabilitation-
      phase II.
AB  - The Heart Monitor is an object-oriented, knowledge-based system designed to
      support the clinical activities of cardiovascular (CV) rehabilitation. The
      original concept was developed as part of graduate research completed in 1992.
      This paper describes the second generation system which is being implemented in
      collaboration with a local heart rehabilitation program. The PC UNIX-based system
      supports an extensive patient database organized by clinical areas. In addition,
      a knowledge base is employed to monitor patient status. Rule-based automated
      reasoning is employed to assess risk factors contraindicative to exercise therapy
      and to monitor administrative and statutory requirements.

PMID- 8563286
TI  - Experience with a mixed semantic/syntactic parser.
AB  - The value of the computerized medical record is derived in part from the
      availability of medical information in a coded form accessible to manipulation by
      processes designed for automated decision support, medical research, and computer
      assistance in the management of health care delivery. To meet these needs medical
      reports captured and stored as natural language documents must be encoded. Below
      we discuss an ongoing formative process aimed at developing a natural language
      understanding system for chest x-ray reports. Comparative data showing the
      progress of this process is presented.

PMID- 8563287
TI  - A rational reconstruction of INTERNIST-I using PROTEGE-II.
AB  - PROTEGE-II is a methodology and a suite of tools that allow developers to build
      and maintain knowledge-based systems in a principled manner. We used PROTEGE-II
      to reconstruct the well-known INTERNIST-I system, demonstrating the role of a
      domain ontology (a framework for specification of a model of an application
      area), a reusable problem-solving method, and declarative mapping relations in
      creating a new, working program. PROTEGE-II generates automatically a domain
      specific knowledge-acquisition tool, which, in the case of the INTERNIST-I
      reconstruction, has much of the functionality of the QMR-KAT knowledge
      acquisition tool. This study provides a means to understand better both the
      PROTEGE-II methodology and the models that underlie INTERNIST-I.

PMID- 8563288
TI  - Enhancing medical database semantics.
AB  - Medical Databases deal with dynamic, heterogeneous and fuzzy data. The modeling
      of such complex domain demands powerful semantic data modeling methodologies.
      This paper describes GSM-Explorer a Case Tool that allows for the creation of
      relational databases using semantic data modeling techniques. GSM Explorer fully
      incorporates the Generic Semantic Data Model-GSM enabling knowledge engineers to
      model the application domain with the abstraction mechanisms of
      generalization/specialization, association and aggregation. The tool generates a
      structure that implements persistent database-objects through the automatic
      generation of customized SQL ANSI scripts that sustain the semantics defined in
      the higher lever. This paper emphasizes the system architecture and the mapping
      of the semantic model into relational tables. The present status of the project
      and its further developments are discussed in the Conclusions.

PMID- 8563289
TI  - Decision-theoretic refinement planning: a new method for clinical decision
      analysis.
AB  - Clinical decision analysis seeks to identify the optimal management strategy by
      modelling the uncertainty and risks entailed in the diagnosis, natural history,
      and treatment of a particular problem or disorder. Decision trees are the most
      frequently used model in clinical decision analysis, but can be tedious to
      construct, cumbersome to use, and computationally prohibitive, especially with
      large, complex decision problems. We present a new method for clinical decision
      analysis that combines the techniques of decision theory and artificial
      intelligence. Our model uses a modular representation of knowledge that
      simplifies model building and enables more fully automated decision making.
      Moreover, the model exploits problem structures to yield better computational
      efficiency. As an example we apply our techniques to the problem of management of
      acute deep venous thrombosis.

PMID- 8563290
TI  - The use of misclassification costs to learn rule-based decision support models
      for cost-effective hospital admission strategies.
AB  - Cost-effective health care is at the forefront of today's important health
      related issues. A research team at the University of Pittsburgh has been
      interested in lowering the cost of medical care by attempting to define a subset
      of patients with community-acquire pneumonia for whom outpatient therapy is
      appropriate and safe. Sensitivity and specificity requirements for this domain
      make it difficult to use rule-based learning algorithms with standard measures of
      performance based on accuracy. This paper describes the use of misclassification
      costs to assist a rule-based machine-learning program in deriving a decision
      support aid for choosing outpatient therapy for patients with community-acquired
      pneumonia.

PMID- 8563291
TI  - Automated identification of episodes of asthma exacerbation for quality
      measurement in a computer-based medical record.
AB  - Harvard Community Health Plan and the Center for Intelligent Information
      Retrieval are developing tools to support automated quality fo care measurement
      from clinical text data. A statistically based text classification system uses
      semantic features in computerized encounter notes to identify acute exacerbations
      of asthma. Individual encounter notes are sorted in bins of highly likely, highly
      unlikely and uncertain likelihood of documenting exacerbation, and then
      aggregated into episodes of exacerbation for frequency analysis. It is estimated
      that this approach could reduce the burden of manual chart review by 65%.

PMID- 8563292
TI  - A rule-based decision support application for laboratory investigations
      management.
AB  - The appropriate management of clinical laboratory requests in specialised
      clinical units often requires the adherence to pre-defined protocols. We
      evaluated the impact of a rule-based expert system for clinical laboratory
      investigations management in a pediatric liver transplantation unit of our
      hospital. After one year, we observed an overall reduction in laboratory
      resources consumption for transplanted patients (-27%) and a decrease in the
      percentage of "STAT" requested tests (-44%). The percentage of tests ordered in
      agreement with the protocols for those patients increased from 33% before the
      introduction of the expert system to 45% when the system was used. The system was
      perceived by the clinicians as increasing the overall benefits in use of clinical
      resources, improving the laboratory data management, and saving time for the
      execution of laboratory ancillary tasks.

PMID- 8563293
TI  - IMPACT: an object-oriented graphical environment for construction of multimedia
      patient interviewing software.
AB  - This paper describes our software for rapid construction of multimedia computer
      interviews. The program, which we call IMPACT, was designed to measure
      preferences for health outcomes using the standard gamble and other decision
      analytic techniques. IMPACT is also a multimedia shell program that allows
      researchers to interactively construct patient interviewing instruments without
      programming or scripting. It supports the integration of text, graphics,
      synthesized speech, digital sound and QuickTime movies into interviewing
      instruments through a point-and-click interface. IMPACT also supports branching
      logic and randomizing the presentation order of materials within an instrument.
      This allows customization of the presentation based on patient responses and
      facilitates experimental designs. Validation studies show that preference
      assessments performed using IMPACT have high test-retest reliability (r = 0.83, n
      = 96). Post-test surveys (n = 52) show that most subjects understand valuation
      methods (86%) and believe that the explanations provided were clear (96%) and
      that methods were reasonable (80%). The majority of subjects thought the
      preference assessment methods were not difficult to use (53%) and would have been
      comfortable using such methods for medical decisions (53%).

PMID- 8563295
TI  - Querying temporal clinical databases with different time granularities: the GCH
      OSQL language.
AB  - There is a need for managing temporal clinical information given at different
      levels of granularity. Different time granularities are also needed in querying
      clinical databases. In this paper, we describe GCH-OSQL (Granular Clinical
      History--Object Structured Query Language), an object-oriented temporally
      oriented extension of SQL. GCH-OSQL is based on an object-oriented temporal data
      model. It allows storage of clinical information at different and mixed
      granularities. GCH-OSQL deals with the valid time of clinical information. GCH
      OSQL offers also a graphical user-interface. It guides different end users, from
      expert to naive, to formulate expressive and correct queries.

PMID- 8563294
TI  - Sampling strategies in a statistical approach to clinical classification.
AB  - This paper studies the sampling strategies for the Expert Network (EexNet), a
      statistical learning system used for patient record classification at the Mayo
      Clinic. The goal is to achieve high accuracy classification at an affordable
      computational cost in very large applications. The learning curves of ExpNet were
      observed with respect to the choice of training resources, the size, vocabulary
      coverage and category coverage of a training set, and the category distribution
      over training instances. A method combining advantages of different sampling
      strategies is proposed and evaluated using a large training corpus. As a result,
      Expert Network has achieved its nearly-optimal classification accuracy (measured
      by average precision) using a relatively small training set, with a fast real
      time response which satisfies the needs of human-machine interaction.

PMID- 8563296
TI  - A comparison of the temporal expressiveness of three database query methods.
AB  - Time is a multifaceted phenomenon that developers of clinical decision-support
      systems can model at various levels of complexity. An unresolved issue for the
      design of clinical databases is whether the underlying data model should support
      interval semantics. In this paper, we examine whether interval-based operations
      are required for querying protocol-based conditions. We report on an analysis of
      a set of 256 eligibility criteria that the T-HELPER system uses to screen
      patients for enrollment in eight clinical-trial protocols for HIV disease. We
      consider three data-manipulation methods for temporal querying: the consensus
      query representation Arden Syntax, the commercial standard query language SQL,
      and the temporal query language TimeLineSQL (TLSQL). We compare the ability of
      these three query methods to express the eligibility criteria. Seventy nine
      percent of the 256 criteria require operations on time stamps. These temporal
      conditions comprise four distinct patterns, two of which use interval-based data.
      Our analysis indicates that the Arden Syntax can query the two non-interval
      patterns, which represent 54% of the temporal conditions. Timepoint comparisons
      formulated in SQL can instantiate the two non-interval patterns and one interval
      pattern, which encompass 96% of the temporal conditions. TLSQL, which supports an
      interval-based model of time, can express all four types of temporal patterns.
      Our results demonstrate that the T-HELPER system requires simple temporal
      operations for most protocol-based queries. Of the three approaches tested, TLSQL
      is the only query method that is sufficiently expressive for the temporal
      conditions in this system.

PMID- 8563297
TI  - Acts and knowledge management in the NUCLEUS hospital information system.
AB  - NUCLEUS is a project completed in June 1995 in the frame of the European
      Community programme AIM (Advanced Informatics in Medicine). The main result of
      NUCLEUS is a prototype of an integrated patient dossier. Together with this
      patient dossier, facilities have been developed for its customisation by the
      various categories of end-users. A semantic model has been designed to guide and
      control the exploitation of data, and ensures the overall integrity of the
      information system.

PMID- 8563298
TI  - Transforms of the computerized patient record data model: from transactions to
      analytical processing.
AB  - The design of Computerized Patient Record databases needs to be different
      depending on whether the focus of the database is transaction processing or
      analytical processing. Transaction processing includes the operational use of
      databases for single patient update during clinical encounters. Analytical
      processing includes cross-patient querying for research or clinical management.
      These different design needs are defined. A case study is presented for the
      methodology that transforms transaction databases to analytical ones. The
      resulting analytical design is argued to be successfully evaluated according to
      specific criteria of useability and maintainability. This methodology is easily
      replicated in any relational database environment.

PMID- 8563299
TI  - Architectural requirements for a multipurpose natural language processor in the
      clinical environment.
AB  - A considerable amount of research has been concerned with the development of
      natural language systems to automate the encoding of clinical information that
      occurs in textual form. The task is very complex, and not many language
      processors are used routinely within clinical information systems. Those systems
      that are operational, have been implemented in narrow domains for particular
      applications. For a system to be truly useful, it should be designed so that it
      could be widely used within the clinical environment. This paper examines
      architectural requirements we have identified as being necessary for portability
      and describes the architecture of the system we developed. Our system was
      designed so that it could be used in different domains to serve a variety of
      applications. It has been integrated with the clinical information system at
      Columbia-Presbyterian Medical Center where it routinely encodes clinical
      information from radiological reports of patients.

PMID- 8563300
TI  - A distributed, scalable, community care network architecture for wide-area
      electronic patient records: modeling and simulation.
AB  - Principal systems issues relative to computerizing patient medical records that
      are yet to be addressed in the scientific literature include (1) the
      characteristics of networks, i.e. bandwidth and capacity, and their impact on the
      performance of the system, (2) the architecture and the underlying algorithm of
      the system, (3) the location and migration of medical records, (4) scalability of
      the system, and (5) the nature of the performance variation under heavy and light
      use of the network. Key parameters that affect performance include the number of
      patients, doctors, frequency of patient visits, and the number of electronic
      queries and record entries initiated during a patient-doctor interaction episode.
      This paper presents AMPReD, a Distributed, Scalable, Community Care Network
      Architecture that aims to provide Real-Time Access to Geographically-Dispersed
      Patient Medical Records. The AMPReD model includes stationary hospitals and
      medical clinics, mobile clinics, migrating doctors as well as patients, the
      communications network, and the patient medical record database. AMPReD's goals
      include (1) the accurate modeling of the propagation of medical records and (2)
      providing real-time access to patient medical records from anywhere in the
      system. To achieve these goals, an asynchronous, distributed algorithm must be
      developed that achieves concurrent access of multiple, autonomous databases.
      AMPReD is modeled and simulated for a representative community care network on a
      network of workstations configured as a loosely-coupled parallel processor, for
      different parametric combinations of number of doctors, patients, and number of
      queries or record entries generated corresponding to every patient-doctor
      interaction episode. AMPReD defines and obtains key performance measures
      including the idle times of the doctors, patient waiting times, the access times
      of queries as functions of their sizes, and the growth of the databases. In
      addition, AMPReD also measures the deviation of the actual time required for a
      patient-doctor interaction episode from the scheduled interaction interval, as a
      function of the network load. For the representative system selected, performance
      measures indicate that the network, utilizing 1/2T1 links, and the database
      system poses no bottleneck to the system even where the number of doctors and
      patients within a 30 minute interval are chosen at 192 and 200 respectively. A T1
      is a standard, digital, transmission link that is rated at 1.44Mbits/sec.

PMID- 8563301
TI  - A multi-lingual architecture for building a normalised conceptual representation
      from medical language.
AB  - The overall goal of MENELAS is to provide better access to the information
      contained in natural language patient discharge summaries (PDSs), through the
      design and implementation of a prototype able to analyse medical texts. The
      approach taken by MENELAS is based on the following key principles: (i) to
      maximise the usefulness of natural language analysis and the usability of its
      results, the output of natural language analysis must be a normalised conceptual
      representation of medical information; and (ii) to maximise the reuse of
      resources, language analysis should be domain-independent and conceptual
      representation should be language-independent. This paper discusses the results
      obtained and the issues raised when implementing these principles during the
      project.

PMID- 8563302
TI  - Treatment planning: implications for structure of the CPR.
AB  - The work of developing a specification for treatment and care planning software
      reveals lacunae in current structural conceptualizations of the computer-based
      patient record (CPR). A written treatment plan is ubiquitous in psychiatric
      settings, highly structured, and in theory, ideally suited to computerization.
      Treatment and care planning are also prevalent in nursing, rehabilitation, and
      long-term care. Treatment plans justify treatment with clinical data, and
      document goals, methods, and treatment outcomes. Implementing computer-based
      planning has been more difficult than first thought because present CPR systems
      do not support data schemes suited for integrating treatment plans with the
      general patient record. The CPR for general medical care will advance when it can
      support a treatment plan. Gaps in current CPR design exposed by requirements
      analysis for a multidisciplinary, team-based treatment planning system are
      identified.

PMID- 8563303
TI  - Evaluation of an object-based data model implemented over a proprietary, legacy
      data model.
AB  - Most computerized medical information today is contained in legacy systems. As
      vendors slowly move to open systems, legacy systems remain in use and contain
      valuable information. This paper evaluates the use of an object model imposed on
      an existing database to improve the ease with which data can be accessed. This
      study demonstrates that data elements can be retrieved without specific
      programming knowledge of the underlying data structure. It also suggests that
      underlying data structures can be changed without updating application code.
      Programs written using the object model were easier to program but ran greater
      than one order of magnitude slower than traditionally coded programs. In this
      paper, the legacy information system is introduced, the methods used to implement
      and evaluate the object-based data model are explained, and the results and
      conclusions are presented.

PMID- 8563304
TI  - Validity and reliability of standard terms and codes for patient care data.
AB  - A set of standard terms and codes for patient care data was derived from care
      planning and documentation materials submitted by 9 hospitals. The set contained
      329 terms for Patient Problems, 308 terms for Patient Outcomes, and 1261 terms
      for Patient Care Actions. Six of the hospitals participated in a test of validity
      and reliability of the standard terms and codes. Manual audits were conducted on
      465 patient records from two services in each hospital. All auditors achieved
      acceptable accuracy in coding. The auditors identified 18,995 items in the
      patient records as representing statements of Patient Problems, Patient Outcomes,
      or Patient Care Actions. The standard terms and codes matched 99.1% of these
      items. Thus, for the services audited, the standard terms and codes provided a
      valid representation of the Patient Problems, Patient Outcomes, and Patient Care
      Actions in the patient records.

PMID- 8563305
TI  - Converting a legacy system database into relational format to enhance query
      efficiency.
AB  - The analysis of clinical data collected over time can provide important insight
      into the health care process. Unfortunately, much of the electronic clinical data
      that exists today is stored in legacy systems, making it difficult to access and
      share the information. An approach is needed to improve the accessibility of
      electronic data stored in legacy system databases. In this study, a legacy
      database is converted into a relational format in the personal computer
      environment. The impact of such a conversion on query performance is evaluated,
      and issues that need to be considered when converting a legacy system database
      are identified.

PMID- 8563306
TI  - An object oriented computer-based patient record reference model.
AB  - In the context of health care information systems based on client/server
      architecture, we address the problem of a common Computer-based Patient Record
      (CPR). We define it as a collection of faithful observations about patients care,
      with respect to the free expression of physicians. This CPR model supports
      several views of the medical data, in order to provide applications with a
      comprehensive and standardized access to distributed patient data. Finally, we
      validated our CPR approach as a primary data model server for an application for
      hypertensive patient management.

PMID- 8563307
TI  - A comparison of problem lists generated by physicians, nurses, and patients:
      implications for CPR systems.
AB  - Using a sample of 201 patients hospitalized for Pneumocystis carinii pneumonia,
      this study describes problem lists generated by physicians and examines the
      overlap among problem lists generated by physicians, nurses, and patients. The
      findings indicate that the majority of patients in this sample had at least one
      problem that occurred in more than one problem list. Problems that most
      frequently appeared in more than one problem list were those related to the
      medical diagnosis of Pneumocystis carinii pneumonia and its associated
      physiological symptoms. Problems which occurred uniquely in the nurse problem
      list were knowledge deficit and potential for injury. Thirty-four percent of the
      patients identified at least one psychosocial problem that did not occur in
      either the physician- or nurse-generated problem lists. The study findings
      demonstrate that while there is overlap among the problem lists in problems
      related to the principal medical diagnoses, the nurse- and patient-generated
      problem lists include unique problems which provide additional significant
      information related to patient status that has the potential to impact patient
      outcomes. These findings suggest that a unified, nonredundant, multidisciplinary
      problem list is warranted in order to provide a comprehensive view of the patient
      for computer-based patient record (CPR) systems. Appropriate data models and
      comprehensive controlled vocabularies are needed to support the multiple uses of
      the problem list for CPR systems.

PMID- 8563308
TI  - Extending a clinical repository to include multiple sites.
AB  - With the consolidation of health care organizations and services, a clinical
      repository comprising data from a single site is no longer sufficient. Individual
      patient data are now spread across multiple sites comprising a single enterprise.
      Users require an integrated view, or at least a common view, of these clinical
      data across multiple sites. Many issues arise when one tries to merge data from
      multiple, distinct organizations into an existing schema. We have addressed these
      issues while extending our clinical repository for Barnes Hospital with data from
      Jewish Hospital, both of which are members of the recently formed BJC Health
      System. We describe the architecture of our existing repository, approaches and
      issues in extending this repository to include multiple sites, and the specific
      issues we addressed in our system.

PMID- 8563309
TI  - Creating temporal abstractions in three clinical information systems.
AB  - Modern clinical information system developers recognize the need to associate
      temporal information with clinical data. However, specific clinical systems
      capture different temporal features using a variety of data modeling techniques.
      Two commonly used methods to represent temporal information are point-based
      events and interval-based durations. We recently implemented a rule-based expert
      system for drug dose monitoring on three clinical information systems. The expert
      system requires both static drug dosing information (drug name, amount, route,
      frequency) and temporal dosing information (duration of therapy, renewals,
      restarts). Our design goal was to use the same expert system code on all three
      information systems by defining a common database schema to hide differences in
      the original systems' data models. Although we have been successful in mapping
      clinical data from these three source systems into a unified temporal data
      representation, we describe how differences in handling time within the three
      clinical systems made this goal difficult to achieve.

PMID- 8563310
TI  - Comparison of probabilistic and deterministic record linkage in the development
      of a statewide trauma registry.
AB  - We have been working to develop a statewide injury surveillance system using not
      only hospital-based trauma registries but also other sources of data (including
      ambulance run reports, hospital discharge abstracts, and death certificates). For
      this purpose, a commercially available probabilistic matching program was
      compared to the deterministic program described previously. Using the same data
      preprocessing and linkage strategy, we programmed the probabilistic software to
      perform the matching step and compared the results with those obtained from the
      previously tested program. The outcomes using our data were similar, but we
      expect the probabilistic program to be more adaptable for general use, especially
      if large amounts of data must be linked.

PMID- 8563311
TI  - A data model that captures clinical reasoning about patient problems.
AB  - We describe a data model that has been implemented for the CPMC Ambulatory Care
      System, and exemplify its function for patient problems. The model captures some
      nuances of clinical thinking about patients that are not accommodated in most
      other models, such as an evolution of clinical understanding about patient
      problems. A record of this understanding has clinical utility, and serves
      research interests as well as medical audit concerns. The model is described with
      an example, and advantages and limitations in the current implementation are
      discussed.

PMID- 8563312
TI  - Can one patient record accommodate the diversity of specialized care?
AB  - Despite a quarter century of developments, few specialists directly use a
      computerized patient record, that fully replaces the paper chart. Because of the
      diversity of domains in specialized care, medical decision-making and the
      continuity of care may suffer from scattering of patient data over various
      records. The challenge was to develop a computerized patient record, that would
      be versatile enough to tailor it to specific needs, while keeping it uniform
      enough to permit physicians to share data on the same patient. In our CPR, the
      key that reconciles versatility with uniformity lies in the design of the data
      model. The CPR consists of a mother record with specialized sub-records, that all
      share the same data model. A physician can enlarge his scope for decision-making
      by consulting other specialized records on the same patient or by viewing the
      combined information of all sub-records without the need to convert data or to
      familiarize himself with different interfaces.

PMID- 8563313
TI  - A findings model for an ambulatory pediatric record: essential data, relational
      modeling, and vocabulary considerations.
AB  - Effective, computer-based representation of clinical observations requires
      balancing the advantages of structured, coded descriptions against those of free
      text narrative. An essential data set of relevant signs and symptoms was defined
      by a multidisciplinary group based on management goals published in a national
      guideline to meet the needs of clinicians in the Spina Bifida Clinic at Yale-New
      Haven Hospital. These core data elements are stored in a structured format.
      Additional material is stored as free text. A relational schema was devised that
      permits storage of both coded findings and narrative. Symptoms and signs are
      represented as subtypes of a supertype patient finding entity; they inherit
      common attributes and specialize others. The IVORY vocabulary was supplemented
      and modified to provide terms that describe relevant clinical observations. For
      this application, fields were added that enable predictive data entry of findings
      based on patient age and gender.

PMID- 8563314
TI  - Categorization of free-text problem lists: an effective method of capturing
      clinical data.
AB  - Problem lists assist in organizing patient information in computer based medical
      records. However, in order to use problem lists for billing, research, decision
      support and standardization, a categorization of the problems entered is
      required. We describe the problem list component of our computerized patient
      record, the On-line Medical Record (OMR), which combines a free-text entry
      mechanism with a categorization scheme, using a dictionary containing 846 terms.
      All 118,040 problems entered during the system's six years of use have been
      analyzed, 477 clinicians have entered a mean +/- S.D. of 238 +/- 604 problems
      into 22,311 patient records. The average number of problems in each patient's
      file was 5.1 +/- 3.9. Comments were typed for 80,281 (68%) of the problems,
      ranging in length from 1 to 2456 characters, with a mean length of 98 +/- 110
      characters. Half the problems were entered on the day of the encounter with the
      patient. Overall, 66% of all problems were categorized in relation to terms from
      the problem dictionary. Lexical analysis of all problem names showed that 80%
      could be mapped to Meta 1.4, Snomed 3.0 or a pre-release version of Read 3.0. We
      conclude that a problem list entry scheme combining free-text entry and optional
      categorization using a dictionary can result in a high proportion of problems
      being categorized as desired. Improvement of the system by elimination of unused
      dictionary terms and addition of 1000 terms identified by the lexical analysis is
      likely to result in even higher categorization rates.

PMID- 8563315
TI  - Generating penetration path hypotheses for decision support in multiple trauma.
AB  - We present a 3D graphical system that allows users to visualize different
      penetration path hypotheses for (multiple) gunshot or stab wounds, using a 3D
      graphical model of a human body with appropriate anatomical structures. The
      system also identifies the anatomical structures associated with each hypothesis.
      The various penetration path hypotheses follow from a combinatorial analysis of
      the set of surface wounds. The affected structures are determined by performing a
      detailed interpenetration analysis between 3D models of a penetration path and
      each anatomical structure within the body.

PMID- 8563316
TI  - Applying a controlled medical terminology to a distributed, production clinical
      information system.
AB  - To maximize the value of computerized medical records systems, an organizing
      structure is needed. That structure can be provided by a controlled medical
      terminology (CMT). At Columbia-Presbyterian Medical Center, we have been
      employing a controlled medical terminology, our Medical Entities Dictionary
      (MED), to mediate the storage and retrieval of patient data and enable decision
      support applications. This paper describes how the MED is actually used for data
      management in our distributed clinical information systems environment. Our
      system tools which access the MED for production purposes facilitate the mapping
      of terms from many sources to a uniform representation of concepts and also
      return information about the relationships between concepts. Applications which
      access a CMT for production purposes should be optimized for performance in high
      volume settings, fault tolerant, synchronizable, extensible, portable, and
      maintainable. We briefly describe our system architecture and then demonstrate
      how we utilize the MED for translation and semantic information as data is moved
      into and out of our patient database. We discuss our current tools and present a
      preview of the next generation of applications which will manage access to the
      MED for our production systems.

PMID- 8563317
TI  - Representation of clinical problem assessment phrases in U.S. family practice
      using Read version 3.1 terms: a preliminary study.
AB  - The Read Codes from the United Kingdom are a comprehensive clinical vocabulary,
      and one of the most likely candidates for adoption as a standard for use in
      Computer-Based Patient Record (CPR) systems. The new version 3.1 codes represent
      a major enhancement to the content and structure of the coding system, including
      incorporation of a new hierarchy and an explicit model for the use of qualifier
      terms. This is a preliminary study investigating the suitability of these codes
      for representing clinical problem assessment phrases in U.S. family practice.
      Problem assessment phrases from outpatient progress notes were encoded into the
      equivalent Read terms. The problem assessment phrases were evaluated for
      complexity and clarity. The coded representations of the phrases were evaluated
      for clinical acceptability. A list of coding difficulties was compiled. The most
      common difficulties were (1) qualifier terms present but not allowable for that
      Read concept (24%), and (2) qualifier terms not present (20%). British spelling
      and abbreviation variants were noted, but were relatively insignificant. The Read
      codes appear to be suitable for use in U.S. primary care practice with fairly
      minor modifications, but further development is required to expand the content
      and structure of the model for qualifier terms.

PMID- 8563318
TI  - Implementing a low-cost computer-based patient record: a controlled vocabulary
      reduces data base design complexity.
AB  - In order to build a computer-based patient record (CPR) system suitable for use
      in solo and small group practice settings it is necessary to use development
      methods that minimize cost. Design complexity is a major source of high cost.
      Reducing complexity should result in lower development, deployment and
      maintenance costs as well as higher reliability. We have developed a simplified
      relational model and have used that model, in conjunction with a controlled
      vocabulary, to implement a CPR that can capture and store patient examinations
      and other forms of clinical notes as well as laboratory and other test results.
      The information can be viewed in a familiar document format and it can accessed
      for other types of processing using standard Structured Query Language (SQL)
      techniques. The database, as implemented, uses inexpensive components resulting
      in a system that is not prohibitively expensive for solo practitioners and small
      groups. In addition the architecture is scaleable and can accommodate very large
      numbers of patients and practitioners.

PMID- 8563319
TI  - Reasons for the loss of sensitivity and specificity of methodologic MeSH terms
      and textwords in MEDLINE.
AB  - OBJECTIVE: To determine the reasons for the loss of sensitivity and specificity
      of methodologic MeSH terms and textwords in MEDLINE for identifying sound
      clinical studies of the etiology, prognosis, diagnosis, prevention, or treatment
      of disorders in adult general medicine. DESIGN: Analytic survey of the
      information retrieval properties of methodologic MeSH terms and textwords
      selected to detect studies meeting basic methodologic criteria for direct
      clinical use in general adult medicine. MEASURES: Frequency of non-use and misuse
      of relevant methodologic MeSH terms and textwords among studies meeting and not
      meeting the basic criteria for clinical practice as determined by the manual
      review (the gold standard) of all articles in 10 internal and general medicine
      journals for 1986 and 1991. RESULTS: Loss of sensitivity due to the non-use of
      relevant methodologic terms among articles meeting basic methodologic criteria
      was more pronounced in the areas of diagnosis, prognosis, and etiology than
      treatment in 1991 and 1986. The use of relevant methodologic terms has improved
      from 1986 to 1991 in all areas except prognosis. Loss of specificity due to the
      use of relevant methodologic terms among articles not meeting basic methodologic
      criteria occurred most frequently in the areas of treatment and etiology.
      CONCLUSIONS: Although the appropriate use of methodologic MeSH and textwords has
      improved from 1986 to 1991 among studies meeting basic methodologic criteria for
      direct clinical use in general adult medicine much improvement is still needed in
      the areas of diagnosis, prognosis, and etiology. Improvement is needed in
      assigning the relevant methodologic index terms to studies that meet the methods
      criteria and in having the authors use the relevant methodologic textwords in the
      title or abstract. Some improvement is also needed in not using methodologic
      terms when the study clearly does not meet the methods criteria.

PMID- 8563320
TI  - Using agent-based technology to create a cost effective, integrated, multimedia
      view of the electronic medical record.
AB  - Image Engine is multi-user, client-server database for the storage, retrieval and
      sharing of a wide range of digitized biomedical images under development at the
      University of Pittsburgh. This paper provides an overview of the system and
      describes the use of agent-based technology to integrate clinical information
      from the Image Engine database and the MARS clinical information system at the
      University of Pittsburgh Medical Center. Agent-mediated links provide a mechanism
      for combining clinical data from multiple databases to create a unified,
      multimedia view of the electronic medical record.

PMID- 8563321
TI  - ARIS: integrating multi-source data for research in andrology.
AB  - Although the concept of distributed systems for the storage of patient data is
      more and more commonly accepted, for some considerable time yet most patient data
      will be stored in centralized rather than departmental systems. An important
      advantage of storage in a central system is hospital-wide access to much of the
      patient data. Disadvantages are however that these data cannot be reviewed
      through one user interface, and that the structure of the data does not lend
      itself to exploitation for other purposes. We describe the implementation of an
      Andrology Research Information System in which these data are integrated in a
      well-structured database facilitating multiple views on the patient data through
      a graphical user interface, and clinical research, quality control and summary
      reports. The data can be analyzed directly using the Hermes workstation. In this
      way the strengths of the centralized system are combined with those of the
      dedicated ARIS system.

PMID- 8563322
TI  - Coding drug effects on laboratory tests for health care information systems.
AB  - Drugs interfere with laboratory diagnostics. This interference is not only
      confusing for clinicians but may lead to wrong diagnoses or treatments as well as
      unnecessary further tests. However, at the moment the drug-laboratory
      interferences are usually ignored in patient care because clinicians do not know
      or remember these properties of drugs. In Turku University Central Hospital we
      are now able to bring this information automatically available for clinicians by
      using a computerized system for linking individual patient medication data with
      laboratory information system. For this purpose, we are building a rule base
      containing the effects of drugs on laboratory tests. In order that the rule base
      would give the maximum benefit for all users, even other hospitals, the data
      included have to be classified and coded properly taking into account the various
      requirements and needs of all users. In this paper we introduce a coding scheme
      for classification and coding of drug effects on laboratory tests.

PMID- 8563323
TI  - PLACO: a cooperative architecture for managing workflow in CCU.
AB  - Computer-Supported Cooperative Work (CSCW) is a multi-disciplinary research theme
      involving software developers, computer scientists, as well as psychologists and
      sociologists. CSCW is devoted to the analysis of interactions among humans when
      performing their work in a collaborative way. The main application fields are
      work organization, healthcare, education and training. The term of Groupware, as
      defined by C.A. Ellis, refers to software that assists groups of people in
      communicating, in collaborating and in coordinating their activities. Our
      objective is to study software architectures allowing task coordination and
      conflict management between participants within a distributed environment, in
      particular medical units. We do not aim to produce a practical system suitable
      for near-term deployment in the Critical Care Unit (CCU), but rather a "proof of
      concept", an experimental system that performs and coordinates a range of
      intelligent planning tasks in CCU activities. The emphasis will be put especially
      on asynchronous cooperation since the work of physicians and nurses is
      discontinuous.

PMID- 8563324
TI  - Enhancement of clinician workflow with computer order entry.
AB  - Physician-operated order entry systems can bring great benefits to an
      institution. Such systems can improve the consistency, accuracy, safety, and cost
      effectiveness of orders. When building or selecting order entry for an
      institution, consideration must be given to the many different scenarios in which
      orders are written and communicated. Transfer, post-op, pre-admission and
      discharge orders have different communication requirements from standard
      inpatient orders. In certain services, orders from a very limited set (such as
      warfarin orders) must be written frequently for a large number of patients.
      Intensive-care patients, chemotherapy patients, and others have particular
      requirements for ordering. A computerized order entry system should respond to
      these requirements in order to promote correct and efficient ordering. We present
      a number of these issues, their specific requirements, and the approach we have
      taken to ensure that the system both supports and enhances workflow.

PMID- 8563325
TI  - On-line documentation of patient care orders.
AB  - The INFORMM NIS (Information Network For Online Retrieval & Medical Management
      Nursing Information System) provides on-line documentation of patient care
      orders. These orders, generated by the nurse or the physician, prescribe direct
      patient care and do not include interdepartmental orders such as laboratory,
      radiology, or pharmacy. The order charting functions support charting efficiency
      by defaulting previous responses so that the user enters only updates to earlier
      findings or new data. Available in tables maintained by NIS staff, charting
      responses provide decision support by suggesting valid results for each order.
      Using point-of-care devices, nursing staff chart patient data that are
      immediately available for review by all authorized members of the health care
      team. These data are printed automatically on computer-generated chart forms
      every twenty-four hours, but may be printed also on demand. Additionally, the
      patient data report, containing patient data entered on-line in the sixteen or
      twenty-four hours immediately preceding the print request, provides a summary
      that is useful for nurses' report and physicians' rounds.

PMID- 8563326
TI  - Contextual inquiry: discovering physicians' true needs.
AB  - Gathering user requirements that represent the true needs of the users is a
      challenge. There are many elicitation methods in use today, but they generally
      are not successful in identifying a comprehensive set of requirements that
      reflect the users' true needs. This paper describes the requirements gathering
      method, Contextual Inquiry, that we used to generate physician requirements for a
      comprehensive Clinical Information System. We feel that this method has
      advantages over traditional techniques such as surveys, questionnaires,
      traditional interviews, and focus groups, in obtaining a more comprehensive
      analysis of the true needs of the users.

PMID- 8563327
TI  - Estimation of pharmacokinetic model parameters.
AB  - This paper addresses the problem of estimating the depth of anesthesia in
      clinical practice where many drugs are used in combination. The aim of the
      project is to use pharmacokinetically-derived data to predict episodes of light
      anesthesia. The weighted linear combination of anesthetic drug concentrations was
      computed using a stochastic pharmacokinetic model. The clinical definition of
      light anesthesia was based on the hemodynamic consequences of autonomic nervous
      system responses to surgical stimuli. A rule-based expert system was used to
      review anesthesia records to determine instances of light anesthesia using
      hemodynamic criteria. It was assumed that light anesthesia was a direct
      consequence of the weighted linear combination of drug concentrations in the
      patient's body that decreased below a certain threshold. We augmented traditional
      two-compartment models with a stochastic component of anesthetics' concentrations
      to compensate for interpatient pharmacokinetic and pharmacodynamic variability. A
      cohort of 532 clinical anesthesia cases was examined and parameters of two
      compartment pharmacokinetic models for 6 intravenously administered anesthetic
      drugs (fentanyl, thiopenthal, morphine, propofol, midazolam, ketamine) were
      estimated, as well as the parameters for 2 inhalational anesthetics (N2O and
      isoflurane). These parameters were then prospectively applied to 22 cases that
      were not used for parameter estimation, and the predictive ability of the
      pharmacokinetic model was determined. The goal of the study is the development of
      a pharmacokinetic model that will be useful in predicting light anesthesia in the
      clinically relevant circumstance where many drugs are used concurrently.

PMID- 8563328
TI  - Interaction and dialogue between the users and the patient record core of
      hospital information system: looking for a solution.
AB  - The lack of good user interface, in terms of both modality of dialogue and system
      behaviour is the major impediment to the acceptance and routine use of the
      computer based patient record (CPR) core of a hospital information system. We
      describe here the adopted approach to face the daily users' needs, overcoming the
      pitfalls of the paper based patient record (PPR), and giving the physicians an
      exhaustive modality for CPR inspection.

PMID- 8563329
TI  - A model curriculum of health care informatics for Dutch higher professional
      education.
AB  - This paper describes the results of a two year project to design a model
      curriculum of health care informatics for Dutch higher professional education.
      The core of the curriculum are sixteen modules which cover the broad range of
      medical informatics and which are closely related to the profiles of the
      professions involved (nursing, physiotherapy, speech therapy, occupational
      therapy and dietetics). The curriculum emphasizes the need of using structured
      data and information to perform tasks in health care delivery and management, for
      which modern information technology is indispensable. The model curriculum will
      enable faculty to redesign existing undergraduate programs and to select the
      contents they see appropriate. In this way we hope that the model curriculum will
      contribute to an innovative attitude of future graduating health care
      professionals. A new three year project just has started to develop learning
      materials using professional health care software based on the sixteen modules of
      the curriculum.

PMID- 8563330
TI  - Summative evaluation of a baccalaureate nursing informatics curriculum.
AB  - This paper describes the fifth stage in the process of designing, implementing
      and evaluating the nursing informatics courses incorporated into a baccalaureate
      nursing program. The challenge is to construct an evolving nursing informatics
      curriculum so as to provide nursing professionals with the foundations for
      affecting health care delivery. The basic components of the curriculum framework
      are information, technology, and clinical care process. Information on the two
      groups of graduates who have completed the four course sequence and the one group
      of graduates who have been in practice will be discussed.

PMID- 8563331
TI  - Modeling respiratory anatomy and physiology in VR.
AB  - In trauma, many injuries impact anatomical structures, which may in turn affect
      physiological processes--not only those processes within the structures, but ones
      occurring in physical proximity to them as well. Our goal is to endow a 3D
      anatomical model with physiological mechanisms to demonstrate such effects. Our
      approach couples deformable object simulation for organs with physiological
      modeling, in a way that supports three-dimensional animated simulation. We
      demonstrate our approach through our current model of respiratory mechanics in a
      virtual 3D environment. Anatomical models that can capture physiological and
      pathophysiological changes can serve as an infrastructure for more detailed
      modeling, as well as benefiting surgical planning, surgical training, and general
      medical education.

PMID- 8563332
TI  - Cost efficient management of educational material.
AB  - We retrospectively examined direct and indirect costs of providing a programmed
      text in Respiratory Pathophysiology using World-Wide Web (WWW) technology as
      compared to printed paper. The direct costs were $3678 and $3988 respectively.
      Neither of these costs includes the substantial cost of original development of
      the educational material. The indirect cost of distributing printed material is
      $1800. The indirect cost for electronic material is $1430 but this assumes an
      institutional commitment to a technology infrastructure which will be used for
      purposes other than just educational material distribution. Given such a
      commitment, educational material can be managed in a way that provides efficient
      distribution at less cost than traditional paper distribution. The effectiveness
      of electronic methods is dependent on usage. A comparison study of use and
      satisfaction of paper and electronic versions of the material is planned.

PMID- 8563333
TI  - Cross-platform hypermedia examinations on the Web.
AB  - The authors developed a multiple-choice medical testing system delivered using
      the World Wide Web. It evolved from an older, single-platform, locally-developed
      computer-based examination. The old system offered a number of advantages over
      traditional paper-based examinations, such as digital graphics and quicker,
      easier scoring. The new system builds on these advantages with its true cross
      platform design and the addition of hypertext learning responses. The benefits of
      this system will increase as more medical educational resources migrate to the
      Web. Faculty and student feedback has been positive. The authors encourage other
      institutions to experiment with Web-based teaching materials, including
      examinations.

PMID- 8563334
TI  - A method for interactive medical instruction utilizing the World Wide Web.
AB  - We describe the implementation of interactive medical teaching programs in
      radiology and histology which utilize the Internet's World Wide Web (WWW). The
      WWW standard hypertext interface allows for simple navigation between related
      documents but does not provide a method for student tracking or question queries.
      Electronic forms, a recent feature of the WWW, provide the means to present
      question documents to remote clients and track student performance. A feature of
      our approach is dynamic creation of HTML documents based upon interaction with
      database applications. The approach allows multiple simultaneous, yet
      asynchronous interactions by geographically dispersed students upon the same
      instructional database and is scalable, providing the capability for multiple
      image/document servers. The security of the database is assured given that it is
      not accessible through the Internet.

PMID- 8563335
TI  - The interactive image tool: adding structure to images.
AB  - The interactive image format and tool were developed by the Stanford University
      Medical Media and Information Technologies (SUMMIT) group to allow medical
      educators to add interactive annotations and outlines to medical cross-sections,
      gross dissections, and clinical images. The interactive image tool (IIT) format
      offers a general specification for adding structural information to images. The
      IIT format has been used to create rich databases of image/structure information
      which are employed in educational software created at SUMMIT. These databases
      consist of information which is re-usable in other applications as well as a
      standalone image database. Future extensions to the IIT format will provide a
      means to organize information based on the structure of that information rather
      than on the arbitrary or haphazard links of current hypertext and hypermedia
      information networks.

PMID- 8563336
TI  - Web-based access to an online atlas of anatomy: the Digital Anatomist Common
      Gateway Interface.
AB  - A World Wide Web Common Gateway Interface package is described for accessing
      existing online interactive atlases of anatomy. The Web interface accesses the
      same 2-D and 3-D images of human neuroanatomy, knee anatomy and thoracic viscera
      that are currently accessed by a custom interactive atlas in distance learning
      courses. Although the Web interface is too slow to replace the existing atlas, it
      provides a parallel access path that has much broader potential for development
      of a distributed distance learning network in anatomy. By maintaining both access
      methods to the same information sources we continue to satisfy the fast
      interactivity needs for our local courses, while at the same time providing a
      migration path to the Web as the capabilities of Web browsers evolve.

PMID- 8563337
TI  - A model for connecting doctors to university based medical resources through the
      Internet.
AB  - Medical Students and academics at large universities have access to rich and
      varied information resources. These resources tend not to be available from off
      campus sites. We have been running a trial to connect practicing doctors to some
      of the medical resources that are available within our university. We are using
      the Internet to facilitate this process. In doing so, a large number of non
      academic, but very practical problems have had to be solved. We examine in
      particular the roles that Internet service providers and Internet information
      providers play in such a project. In particular we describe the factors used in
      advising users on external service providers, and why we as part of a university
      have chosen not to fulfil the internet service provision role ourselves.

PMID- 8563338
TI  - A computer program for the multivariate and graphical monitoring of acid-base
      data in an intensive care unit.
AB  - Monitoring the arterial acid-base status of ICU patients is done by measuring and
      calculating the acid-base variables pH, the partial pressure of carbon-dioxide
      (PCO2) and the bicarbonate-ion concentration ([HCO-3]). Univariate normal
      reference ranges exist for these values. However, it is well known that an exact
      linear relationship exists between pH, the logarithm of PCO2 and the logarithm of
      [HCO-3] values. We developed a computer program for the multivariate evaluation
      and graphical monitoring of these values in an intensive care setting that takes
      this intrinsic two-dimensionality into account. A composite index is introduced
      for the monitoring of all three laboratory values. Moreover, using this index, a
      multivariate statistical reference region based on an unselected population of
      ICU patients was derived.

PMID- 8563339
TI  - Computer-aided learning validation: a CAI-critical mission.
AB  - Despite a marked increase in computer-assisted instructional applications (CAI)
      over the past few years, little attention has been paid to revising traditional
      approaches toward educational testing. This paper reports a CAI project that
      emphasizes integrating the testing and training of visual judgmental capacities
      of health care professionals. It takes advantage of the computer's ability to
      display digital video segments and to record and compare user learning
      accomplishment and at the same time a normative performance scale can be
      developed. The program uses a method which, in addition to validating the
      efficacy of the project itself, collects data and stratifies users' level of
      proficiency by integrating pre-test and post-test modules. Routine incorporation
      of these principles in CAI may provide a more effective means of correctly
      evaluating the individual's mastery of a topic.

PMID- 8563340
TI  - Expert system for management of urinary incontinence in women.
AB  - The purpose of this nursing informatics and outcomes research study was to
      determine the effectiveness of an expert system for disseminating knowledge to
      ambulatory women health care consumers with urinary incontinence. Clinical
      knowledge from the Agency for Health Care Policy and Research (AHCPR) patient
      guideline for urinary incontinence and research literature for behavioral
      treatments provided the knowledge base for the expert system. Two experimental
      groups (booklet and expert system) and one control group were utilized. Study
      results suggest the use of an expert system as one effective communication means
      for disseminating clinical information in an advisory capacity to ambulatory
      women with urinary incontinence.

PMID- 8563341
TI  - Internet for teaching and learning introductory health informatics.
AB  - Internet resources seem attractive for teaching and learning. But are they usable
      and useful in their present form? We explored Internet, in particular its World
      Wide Web (WWW) resources, in a course on "Medical Methodology" (HINF270) for
      students of health information science. This course offers a systematic overview
      of the methodological principles of clinical care. Its broad scope and low depth
      makes this course a reasonable model to explore the limits of WWW resources.
      During the course, students wrote summaries of individual lectures. After
      critiquing and appropriate corrections, the texts were edited with Hypertext Mark
      up Language (HTML) and augmented with links to WWW resources. Grading based on
      the papers, on their improvements through HTML and WWW, and on the provision of
      information on the search experience were incentives to use WWW. A formal
      questionnaire, administered on-line on a voluntary basis, concluded the
      investigation. Results show: 1) Even under considerable pressure to use WWW,
      libraries remain the reference source of choice for research; 2) Internet
      provides entertainment appeal even though practical utility is currently limited;
      3) Technological proficiency with HTML and search engines is perceived as an
      asset; 4) Varying availability of Internet resources, uncertain and varying
      quality of sources, and limited specificity of research results are the major
      disadvantages of WWW. The teaching implications of these findings are discussed.

PMID- 8563342
TI  - Automatic assessment of scintmammographic images using a novelty filter.
AB  - 99mTc-sestamibi scintmammograms provide a powerful non-invasive means for
      detecting breast cancer at early stages. This paper describes an automatic method
      for detecting breast tumors in such mammograms. The proposed method not only
      detects tumors but also classifies non-tumor images as "normal" or "diffuse
      increased uptake" mammograms. The detection method makes use of Kohonen's
      "novelty filter". In this technique an orthogonal vector basis is created from a
      normal set of images. Test images presented to the detection method are described
      as a linear combination of the images in the vector basis. Assuming that the
      image basis is representative of normal patterns, then it can be expected that
      there should be no major differences between a normal test image and its
      corresponding linear combination image. However, if the test image presents an
      abnormal pattern, then it is expected that the "abnormalities" will show as the
      difference between the original test image and the image built from the vector
      basis. In other words, the existing abnormality cannot be explained by the set of
      normal images and comes up as a "novelty." An important part of the proposed
      method are the steps taken for standardizing images before they can be used as
      part of the vector basis. Standardization is the keystone to the success of the
      proposed method, as the novelty filter is very sensitive to changes in shape and
      alignment.

PMID- 8563343
TI  - Description generation of abnormal densities found in radiographs.
AB  - In this paper we present a system for describing renal stones found in
      radiographs. The system generates descriptions that adhere to those generated by
      radiologists. The descriptions are formulated by discovering the spatial
      relationships that exist between the major organs and the renal stones. The
      system consists of three major components. The first is the image processing
      component which is responsible for locating the stone. The second component is
      the inference network minimization component which determines which spatial
      relationships, of all those that exist between the stone and the organs, is the
      most descriptive. The third component is the natural language generation
      component which is responsible for translating the spatial relationships into
      appropriate medical terminology. We will illustrate all these components on
      several examples.

PMID- 8563344
TI  - Automated reconstruction of endoscopic images of the esophagus.
AB  - Endoscopic devices distort the image of a region under examination. Previous work
      has shown that there are computational methods which can precisely reconstruct
      planar structures in a model of the esophagus and that reconstruction in human
      subjects is operator independent. The purpose of this report is to show that much
      of the process can be automated and to provide additional evidence that the
      reconstruction is both accurate and reproducible.

PMID- 8563345
TI  - Hypermedia patient data retrieval and presentation through WWW.
AB  - WWW can be a helpful tool for PACS and HIS data retrieval and presentation. The
      use of gateways to access both text and hypermedia databases (images and video)
      enables fetched data to be presented in virtually any computer system. WWW
      browsers provide a very friendly interface and require little training to
      operate. This paper presents a prototype that uses a SQL gateway for accessing
      relational patient databases. The dataset used here include text data from
      reports of diagnostic procedures as well as pointers to the corresponding images.
      Images can be displayed by the browsers' viewers.

PMID- 8563346
TI  - Health care network communications infrastructure: an engineering design for the
      Military Health Service System.
AB  - The Military Health Service System (MHSS) provides health care for the Department
      of Defense (DOD). This system operates on an annual budget of $15 Billion,
      supports 127 medical treatment facilities (MTFs) and 500 clinics, and provides
      support to 8.7 million beneficiaries worldwide. To support these facilities and
      their patients, the MHSS uses more than 125 different networked automated medical
      systems. These systems rely on a heterogeneous telecommunications infrastructure
      for data communications. With the support of the Defense Medical Information
      Management (DMIM) Program Office, our goal was to identify the network
      requirements for DMIM migration and target systems and design a communications
      infrastructure to support all systems with an integrated network. This work used
      tools from Business Process Reengineering (BPR) and applied it to communications
      infrastructure design for the first time. The methodology and results are
      applicable to any health care enterprise, military or civilian.

PMID- 8563347
TI  - CHIME-Net, the Connecticut Health Information Network: a pilot study.
AB  - CHIME-Net is a state-wide community health information network project which uses
      a frame-relay approach to interfacility and internet connectivity. This is a
      collaborative effort among competitive institutions, which embraces technologies
      new to the health care industry. The experiences of implementation of the CHIME
      Net pilot project are presented as a first milestone for the state-wide effort.

PMID- 8563348
TI  - Cost justification of a community health information network: the ComputerLink
      for AD caregivers.
AB  - Recent studies examined the perceived benefits of the ComputerLink, a specialized
      computer network for caregivers of persons with Alzheimer's Disease. The
      ComputerLink existed as a special service within a free, public access community
      health information network. The issue of "free", however, is debatable. Though
      usage costs were not incurred by the AD caregivers who used ComputerLink, there
      are direct and indirect costs associated with these and other community networks.
      This study will focus on costs incurred at the individual level, recognizing that
      organizations and society also bear community network costs. At this level, the
      primary cost savings occur with the caregiver. The biggest factor determining net
      economic benefits is the extent to which this technology intervention delays or
      prevents institutionalization. Results of this analysis suggest that community
      health networks do return economic and social benefits to their users.

PMID- 8563349
TI  - SmaCS: smart classification system for the design, maintenance and use of complex
      terminologies. Application in pediatric cardiology.
AB  - The development of a generic Smart Classification System (SmaCS) for the design,
      construction, maintenance, and use of complex controlled terminologies is
      described. The ability of SmaCS to create and maintain terminologies that are
      combinations of structured terms and domain-specific knowledge is an important
      aspect of its design. SmaCS can therefore be used both for both controlled data
      collection, using integrity rules included in the terminology, and intelligent
      data-retrieval. The design and implementation of SmaCS and application in the
      domain of pediatric cardiology are described.

PMID- 8563350
TI  - Networking a need: a cost-effective approach to statewide health information
      delivery.
AB  - VTMEDNET is the health information network for the state of Vermont. In response
      to a needs assessment of rural health care providers, it supports e-mail, access
      to knowledge-bases, and the ability to request library services for health care
      providers across the state, regardless of their location or affiliation. For
      Fletcher Allen Health Care affiliates, it also supports access to in-patient
      hospital records. Two thirds of the state's physicians are using the network as
      well as many other health care providers, and, with minimal cost, it has begun to
      meet its goal of improving health care delivery to many of Vermont's citizens.

PMID- 8563351
TI  - The impact of a guideline-driven computer charting system on the emergency care
      of patients with acute low back pain.
AB  - Federal guidelines for the treatment of acute low back pain were locally modified
      and made more specific. These guidelines were then programmed into a rule-based
      computer charting system which provides real-time advice regarding documentation,
      testing, treatment, and disposition of emergency department patients with this
      condition. In a time-series off-on experiment the system was shown to
      significantly improve documentation of the medical record and discharge
      instructions. There was little effect on the appropriateness of testing and
      treatment and the cost of care. These findings contrast with our previous
      experiment using a similar program for the care of health care workers exposed to
      body fluids. In that study both the appropriateness of care and the cost
      effectiveness of care were substantially improved.

PMID- 8563352
TI  - A model for adapting clinical guidelines for electronic implementation in primary
      care.
AB  - Medical informaticians who seek to implement clinical guidelines by computer must
      be aware of a significant gap that exists between guideline development and
      utilization. In order to be effective, guideline recommendations must be followed
      by clinicians; in order for clinicians to follow willingly, they must agree with
      the guidelines. This paper presents a model process for building consensus among
      clinicians that can be used to obtain support for guideline recommendations prior
      to their electronic implementation. This approach involves initial presentation
      of the guidelines by a specialist, iterative cycles of surveying clinicians'
      opinions about the guidelines and revising the guidelines, supervision of the
      process by a practice opinion leader, and final group discussion of the revised
      guidelines to reach consensus. This model was successfully used to adapt
      guidelines for the continuing care of patients with diabetes mellitus that were
      subsequently implemented electronically with broad support of the primary care
      clinicians using them. The model minimized the need for lengthy group discussion
      by surveying individuals' attitudes and working through a practice opinion leader
      to gain consensus support for the guidelines. An efficient approach for
      developing support for guidelines among practitioners will facilitate the
      electronic implementation of guidelines and lead to enhanced compliance with
      guidelines after implementation.

PMID- 8563353
TI  - Using statistical quality control techniques to monitor blood glucose levels.
AB  - Continuous Quality Improvement techniques developed in industry are increasingly
      being applied to the medical field. Statistical process control charts are a CQI
      technique aimed at monitoring a process and its variability. At our hospital,
      statistical quality control charts are being constructed from laboratory blood
      glucose measurements of patients receiving enteral or parenteral nutrition. The
      charts will be used to monitor glucose levels, reveal variations, and illustrate
      the effects of new protocols designed to manage glucose levels.

PMID- 8563354
TI  - DICOM media interchange standards for cardiology: initial interoperability
      demonstration.
AB  - The first multi-vendor demonstration of digital exchange of cardiac image data
      was held in conjunction with the annual scientific sessions of the American
      College of Cardiology (ACC) in March, 1995. This was the culmination of several
      years of effort by the ACC to help extend the DICOM standard to be suitable for
      cardiac images exchanged on removeable media. The software was designed to help
      system implementors with little or no DICOM experience quickly acquire this
      technology. File content can be specified and manipulated in human-readable form,
      and converted as needed to its binary equivalent. Images were selected from those
      submitted from a variety of sources, and a recordable CD (CD-R) created with 30
      echocardiograms and 30 angiograms). A prototype display program was created that
      reads the DICOM directory ("DICOMDIR"), allows user interaction, and decompresses
      the image files. This paper describes the ACC's interoperability demonstration
      with 29 vendors, the CD-R of images that was used, and the software used by the
      participants.

PMID- 8563355
TI  - Evaluation of a telepathology system between Boston (USA) and Dijon (France):
      glass slides versus telediagnostic TV-monitor.
AB  - The objective of this work was to compare diagnoses achieved through the
      traditional methods of current pathology practice versus diagnoses achieved
      through a selection of image on a telediagnostic TV-monitor. The Kappa
      coefficient between the two protocols of k = 0.26 SE(k) = 0.06 z = k/SE(k) = 4.3
      (p < 0.001) allows us to conclude that there is a good reliability between video
      and glass slide diagnoses.

PMID- 8563357
TI  - Cost-benefit ramifications of PACS: do the dollars make sense?

PMID- 8563356
TI  - A client/server system for remote diagnosis of cardiac arrhythmias.
AB  - Health care practitioners are often faced with the task of interpreting complex
      heart rhythms from electrocardiograms (ECGs) produced by 12-lead ECG machines,
      ambulatory (Holter) monitoring systems, and intensive-care unit monitors.
      Usually, the practitioner caring for the patient does not have specialized
      training in cardiology or in ECG interpretation; and commercial programs that
      interpret 12-lead ECGs have been well-documented in the medical literature to
      perform poorly at analyzing cardiac rhythm. We believe that a system capable of
      providing comprehensive ECG interpretation as well as access to online
      consultations will be beneficial to the health care system. We hypothesized that
      we could develop a client-server based telemedicine system capable of providing
      access to (1) an on-line knowledge-based system for remote diagnosis of cardiac
      arrhythmias and (2) an on-line cardiologist for real-time interactive
      consultation using readily available resources on the Internet. Furthermore, we
      hypothesized that Macintosh and Microsoft Windows-based personal computers
      running an X server could function as the delivery platform for the developed
      system. Although we were successful in developing such a system that will run
      efficiently on a UNIX-based work-station, current personal computer X server
      software are not capable of running the system efficiently.

PMID- 8563358
TI  - Use of severity adjusted comparative systems in the development of critical
      pathways.
AB  - This paper has been prepared to present how South Shore Hospital has successfully
      used computerized applications to provide the highest quality patient care in the
      most cost-efficient manner.

PMID- 8563359
TI  - Promoting measure of nursing care workload through computerization.
AB  - In order to obtain a global approach of the patient centered activity and
      relative costs, we propose to add to the DRG a care workload evaluation. Such an
      application was developed and integrated to the automated medical record
      implemented in each medical department of the hospital. The "Soins Infirmiers
      Individualises a la Personne Soignee" (SIIPS) indicator was chosen to estimate
      nursing acuity. Implementation of the application in ten departments and first
      results permit to demonstrate the system feasability and the fiability of this
      indicator. These conclusions conducted us to propose the extension of this
      experimentation to all the clinical departments of the hospital before the end of
      1995.

PMID- 8563360
TI  - Supporting ad-hoc queries in an integrated clinical database.
AB  - Whether caring for patients or conducting research, medical decision-makers need
      access to clinical data. To fulfill that need, commercial software developers
      have produced a wide range of database query tools that differ greatly in
      functionality and cost. Generally, tools that have a greater ability to conceal
      database complexity from the user also require more effort for administrative
      setup. We describe a cost-effective, commercially-available query tool that
      requires no special setup to perform most simple queries, yet can be customized
      to satisfy users' more complex querying requirements.

PMID- 8563361
TI  - A clinical economics workstation for risk-adjusted health care cost management.
AB  - This paper describes a healthcare cost accounting system which is under
      development at Duke University Medical Center. Our approach differs from current
      practice in that this system will dynamically adjust its resource usage estimates
      to compensate for variations in patient risk levels. This adjustment is made
      possible by introducing a new cost accounting concept, Risk-Adjusted Quantity
      (RQ). RQ divides case-level resource usage variances into their risk-based
      component (resource consumption differences attributable to differences in
      patient risk levels) and their non-risk-based component (resource consumption
      differences which cannot be attributed to differences in patient risk levels).
      Because patient risk level is a factor in estimating resource usage, this system
      is able to simultaneously address the financial and quality dimensions of case
      cost management. In effect, cost-effectiveness analysis is incorporated into
      health care cost management.

PMID- 8563362
TI  - Developing an outcomes infrastructure for nursing. The Outcomes Taskforce.
AB  - An infrastructure to support the evaluation of patient care sensitive to the
      intervention of nursing personnel is being developed within a major health
      maintenance organization. In addition to traditional administrative measures of
      care, the database infrastructure will include measures of the patient's
      functional status, knowledge and engagement in care and psychosocial well-being.
      These measures are believed to be particularly sensitive to the independent
      intervention of the nurse. Reported here are the structures in place to monitor
      and support the reliability and validity of the administrative data elements;
      algorithm elements created to account for missing data; the model for the first
      generation of successful practice reports and the results of a study establishing
      the content validity of the clinical data elements.

PMID- 8563363
TI  - Methods for assessing information needs of clinicians in ambulatory care.
AB  - Clinical information systems that provide physicians with relevant information at
      the time and place where decisions are being made can positively affect the
      quality and cost of health care. We have developed an assessment methodology to
      study clinicians' information needs in the context of the work flow and
      operational constraints of the ambulatory care practice environment. We employed
      a combination of methods, including observational studies, process flowcharting,
      semi-structured interviews, and surveys to comprehensively define clinicians'
      needs. Results from our study point to functional requirements not commonly found
      in hospital-based systems, such as access to problem lists and medications,
      computer-based support for health-care team communications, and patient-specific
      instructions and education.

PMID- 8563364
TI  - Prompting for cost-effective test ordering: a randomized controlled trial.
AB  - This randomized, controlled trial tests the efficacy of a computerized prompting
      system for test ordering. The system, makes use of the sensitivity, specificity,
      positive and negative predictive values of tests. It was tested using clinical
      vignettes in an academic family medicine center with first and second year
      residents. We found that there was a 38% decrease in the numbers of tests ordered
      (p < .01) and a 12% decrease in the costs of tests ordered by using the prompting
      system. We suggest that when used at the point of the patient encounter, this
      system has the potential for promoting more appropriate test ordering and for
      saving considerable health care dollars.

PMID- 8563365
TI  - A computer-generated reminder system improves physician compliance with diabetes
      preventive care guidelines.
AB  - Computerized reminder systems have been shown to be effective in improving
      physician compliance with preventive services guidelines. Very little has been
      published about the use of computerized reminders for preventive care in
      diabetes. We implemented a computer-generated reminder system for diabetes care
      guidelines in a randomized controlled study in the outpatient clinics of 35
      internal medicine residents at the University of Utah and Salt Lake Veterans
      Affairs Hospitals. After a six month study period, compliance with the
      recommended care significantly improved in both the intervention group that
      received patient-specific reminders about the guidelines (38.0% at baseline,
      54.9% at follow-up) and the control group that received a nonspecific report
      (34.6% at baseline, 51.0% at follow-up). There was no significant difference
      between the two groups. Both clinic sites showed similar improvement over
      baseline levels of compliance. Residents who completed encounter forms used by
      the system showed a significantly greater improvement in compliance than those
      who did not complete encounter forms (19.7% vs. 7.6%, p = 0.006). The
      improvements in guideline compliance were seen in all areas of diabetes
      preventive care studied, and significant improvements were seen with recommended
      items from the medical history, physical exam, laboratory testing, referrals, and
      patient education. The use of encounter forms by the providers significantly
      improved documented compliance with the guidelines in almost all categories of
      preventive care. These results suggest that computerized reminder systems improve
      compliance with recommended care more by facilitating the documentation of
      clinical findings and the ordering of recommended procedures than by providing
      the clinician with patient-specific information about guideline compliance
      status. Further study is needed to understand the implications of these findings
      to the development of future computerized reminder systems for chronic diseases
      such as diabetes.

PMID- 8563366
TI  - Computerized support of pressure ulcer prevention and treatment protocols.
AB  - Pressure ulcer prevention and treatment protocols were developed and implemented
      at LDS Hospital. While the protocols were initially implemented "on paper",
      compliance was not optimum until the hospital's information system was modified
      to support the clinician in following the new protocols. Preliminary results
      indicate a significant reduction in the incidence of pressure ulcers.

PMID- 8563367
TI  - A decision support tool for antibiotic therapy.
AB  - We developed a decision support tool to assist physicians anticipating the need
      for antibiotic therapy. The initial screen alerts physicians of pertinent patient
      information, provides direct access to other essential medical information, and
      stimulates clinical judgment by suggesting an antibiotic regimen. The decision
      support tool also suggests the dose and interval for any ordered antibiotics
      selected by the physicians. During a 7-month pilot study, all antibiotics for
      patients admitted to the Shock/Trauma/Respiratory Intensive Care Unit (STRICU)
      were ordered using the decision support tool. Clinical data from the study period
      and a 12-month control period (the previous year) were collected and compared.
      The decision support tool was used to order antibiotics 588 times during the
      study period and the suggested antibiotics were used 218 (37%) times. The
      computer suggested dosages were used over 90% of the time. The mean cost of
      antibiotics was $87.00 (p < 0.04) less per patient during the study period as
      compared to the control period. Prospective assessment revealed only 3 antibiotic
      adverse drug events (ADEs) (0.9%) among 336 study patients as compared to 15 ADEs
      (2.4%) among 626 control patients (p = 0.164).

PMID- 8563368
TI  - The effects of a computer-assisted reminder system on patient compliance with
      recommended health maintenance procedures.
AB  - In June of 1993 we implemented a computer-assisted reminder system in the
      outpatient clinic of an 18 resident family practice training program. The system
      notifies both patients and physicians of recommended health maintenance
      procedures. In the 22 months following implementation we documented a rapid
      increase in physician and patient compliance with several disease screening and
      prevention services. Despite high physician compliance, we were unable to
      increase patient compliance rates above 70% for any procedure. At the end of the
      study period patient compliance varied from a low of 26.7% for sigmoidoscopy to a
      high of 61.7% for pneumococcal pneumonia vaccination. We feel this study has
      important implications for the US Public Health Service's preventive services
      screening goals for the year 2000.

PMID- 8563370
TI  - Evaluation of a belief-network-based reminder system that learns from utility
      feedback.
AB  - PRETRIEVE is a belief-network-based, unsolicited information-retrieval system
      that performs machine learning based on user feedback. We report here on the
      document-ordering and document-retrieval performance of PRETRIEVE. We developed a
      test collection of 410 judgments of document utility in a simulated medical order
      entry context. We characterized the validity of these judgments, which were
      elicited from domain experts, by measuring interrater and intrarater
      reproducibility. We developed a measure of the quality of document orderings
      similar to the ROC-curve analysis used to evaluate document-retrieval systems. We
      found that the ordering performance of the PRETRIEVE system was (1) substantially
      better than random, (2) somewhat less than ideal, and (3) superior to that of
      versions of the PRETRIEVE system that used relevance feedback instead of utility
      feedback. Under a set of assumptions, which we make explicit, we found that the
      documents retrieved by a version of PRETRIEVE that modeled time cost were of
      higher utility than those retrieved by a similar rule-based system.

PMID- 8563369
TI  - Lowering physician hospital resource consumption using low-cost low-technology
      computing.
AB  - Anderson Area Medical Center physicians have been provided disease and procedure
      specific profiles of their practice experience for more than five years. For four
      years, physicians were provided reporting, in a variety of formats, detailing
      their clinical outcomes and consumption of hospital resources in treating
      patients with acute myocardial infarction (AMI), pneumonia, cholecystectomy,
      stroke, congestive heart failure (CHF), and total hip replacement. For the past
      eighteen months physicians have been provided a uniform format of monthly
      physician-specific reporting for stroke, AMI, pneumonia, diabetes, CHF,
      cholecystectomy, total hip replacement, newborn delivery, angina, and hernia
      repair. Using only a modest PC platform with database, word processing, and
      graphics programs operating in a DOS environment, an effective disease/procedure
      reporting program is provided to medical staff with 3 person-days of effort per
      month.

PMID- 8563371
TI  - Semantic visualization of oncology knowledge sources.
AB  - Visualization of knowledge sources can have a substantial impact on the use of
      such sources at the point of care. This is because barriers to use at the point
      of care include hours required to master the electronic interfaces to those
      sources, and minutes required to master the electronic interfaces to those
      sources, and minutes required to accomplish any one retrieval. For a system to be
      used regularly at the point of care, therefore, it must be intuitive and fast.
      This paper presents a three dimensional interface to oncology knowledge sources
      that aims to meet this challenge.

PMID- 8563372
TI  - MCAT--a multimedia cardiac angiogram tool.
AB  - In this article, we present the prototype of the Multimedia Cardiac Angiogram
      Tool (MCAT). The MCAT provides capabilities for reviewing angiograms recorded at
      a cardiac catheterization laboratory. A doctor can use MCAT to annotate
      angiograms with audio, text, and graphics. He/she can selectively package the
      annotated multimedia angiograms into a document, save it as the record for the
      visit or use it for case presentations, or send it to another doctor over a
      network. MCAT streamlines data collection at a cath lab and is intended to
      improve the efficiency of communication and collaboration between doctors. This
      paper describes the design, implementation, and future directions of the
      prototype.

PMID- 8563373
TI  - The Constellation Project: experience and evaluation of personal digital
      assistants in the clinical environment.

PMID- 8563374
TI  - Evaluation of an expert system producing geometric solids as output.
AB  - This paper reports the evaluation of an expert system whose output is a three
      dimensional geometric solid. Evaluating such an output emphasizes the problems of
      establishing a comparison standard, and of identifying and classifying deviations
      from that standard. Our evaluation design used a panel of physicians for the
      first task and a separate panel of expert judges for the second. We found that
      multi-parameter or multi-dimensional expert system outputs, such as this one, may
      result in lower overall performance scores and increased variation in
      acceptability to different physicians. We surmise that these effects are a
      consequence of the higher number of factors which may be deemed unacceptable. The
      effects appear, however, to be equal for computer and human output. This
      evaluation design is thus applicable to other expert systems producing similarly
      complex output.

PMID- 8563375
TI  - Health system re-engineering: a CPRS economic decision model.
AB  - The fundamental problem with the health care delivery system remains too little
      health delivered for too great a cost. Information essential to sound clinical
      and administrative decision making is too frequently missing at the time and
      place of decision. Automated systems offer opportunities both to improve health
      and to reduce cost through effective and efficient information management.
      Information systems are the enabling technology for those business practice
      changes which improve the benefit-cost profile of a re-engineered delivery
      system. The Computer-based Patient Record (CPR) is the organizing framework of an
      enterprise-wide health information system. Since information management is a core
      function of the health care enterprise, evaluation of the CPR should include its
      impact on the value of health outcomes and contribution to the organizational
      mission, rather than solely by benefits which accrue within the delivery system.
      This paper proposes a model to measure the impact of information technology and
      specifically a CPR on a re-engineered health care delivery system.

PMID- 8563376
TI  - A randomized evaluation of a computer-based physician's workstation: design
      considerations and baseline results.
AB  - We are performing a randomized, controlled trial of a Physician's Workstation
      (PWS), an ambulatory care information system, developed for use in the General
      Medical Clinic (GMC) of the Palo Alto VA. Goals for the project include selecting
      appropriate outcome variables and developing a statistically powerful
      experimental design with a limited number of subjects. As PWS provides real-time
      drug-ordering advice, we retrospectively examined drug costs and drug-drug
      interactions in order to select outcome variables sensitive to our short-term
      intervention as well as to estimate the statistical efficiency of alternative
      design possibilities. Drug cost data revealed the mean daily cost per physician
      per patient was 99.3 cents +/- 13.4 cents, with a range from 0.77 cent to 1.37
      cents. The rate of major interactions per prescription for each physician was
      2.9% +/- 1%, with a range from 1.5% to 4.8%. Based on these baseline analyses, we
      selected a two-period parallel design for the evaluation, which maximized
      statistical power while minimizing sources of bias.

PMID- 8563377
TI  - Evaluation of Community Care Network (CCN) system in a rural health care setting.
AB  - Concurrent Engineering Research Center (CERC), under the sponsorship of NLM
      (National Library of Medicine) is in the process of developing a computerized
      patient record system for a clinical environment distributed in rural West
      Virginia. This realization of the CCN (Community Care Network), besides providing
      computer-based patient records accessible from a chain of clinics and one
      hospital, supports collaborative health care processes like referral and
      consulting. To evaluate the effectiveness of the system, a study was designed and
      is in the process of being executed. Three surveys were designed to provide
      subjective measures, and four experiments for collecting objective data. Data
      collection is taking place in several phases: baseline data are collected before
      the system is deployed; the process is repeated with minimal changes three, then
      six months later or as often as new versions of the system are installed. Results
      are then to be compared, using whenever possible matching techniques (i.e. the
      preliminary data collected on a provider will be matched with the data collected
      later on the same provider). Surveys are conducted through questionnaires
      distributed to providers and nurses and person-to-person interviews of the
      patients. The time spent on patient-chart related activities is measured by work
      sampling, aided by a computer application running on a laptop PC. Information
      about missing patient record parts is collected by the providers, the frequency
      by which new features of the computerized system are used will be logged by the
      system itself and clinical outcome measures will be studied from the results of
      the clinics' own patient chart audits. Preliminary results of the surveys and
      plans for the immediate and distant future are discussed at the end of the paper.

PMID- 8563378
TI  - Hand-held computing in the patient care setting: a pilot project.
AB  - Direct patient care has not fully benefited from a number of recent advances in
      modern technology. Many of the normal data collections tasks carried out by care
      providers are still done with manual, error-prone procedures. In addition, the
      ability to consolidate or represent patient data in a meaningful and timely
      fashion as required by managed care expectations is unavailable. The reported
      work attempts to address these problems with the application of new hand-held
      computing technology.

PMID- 8563379
TI  - Cost-effective health information systems: user-driven internal development at
      the University of Iowa.
AB  - GOALS: The Information Network For Online Retrieval & Medical Management
      (INFORMM), health information system (HIS) for the University of Iowa Hospitals
      and Clinics (UIHC), was analyzed with regard to development of a Computer-Based
      Patient Record (CBPR) in a cost-effective manner. The analysis: i) profiles
      INFORMM system functionality; ii) displays INFORMM use and satisfaction among
      physicians, nurses, and other hospital employees; iii) characterizes dynamics
      affecting INFORMM growth; and iv) evaluates the cost of a system of internal
      development of software. DATA SOURCES: INFORMM utilization for 1989, 1994, and
      1995; service requests from users for the years 1985, 1990, and 1994; 1994 MECON
      PEERx data; gap analysis user survey conducted by an independent consulting firm.
      MAIN RESULTS: 1) Physician use has been dominated by a single function: retrieval
      of laboratory results. 2) Nurse use of the system was more diverse. A recent
      surge of nurse and physician use resulted from the introduction of online
      documentation of nursing care. 3) Overall use has been predominantly by non
      clinician users, no one function dominating their pattern of use. 4) User service
      requests were predominantly from the non-clinician group of users. Requests from
      non-physician groups have been coordinated by a limited number of representatives
      of those groups, unlike requests from physicians. 5) The UIHC HIS ranked high in
      user satisfaction. 6) The overall cost of the UIHC HIS system is relatively low
      as a percentage of the gross operating budget or as a ratio to the volume of
      patient activities in this medical center. CONCLUSIONS: Internal development of
      INFORMM has been a cost-effective solution to the information demands of nursing
      staff and other users. INFORMM system composition reflects the quantity and
      organization of user requests. Satisfying the needs of physicians requires a
      change in the manner in which physician needs are assessed.

PMID- 8563380
TI  - Acceptance and performance by clinicians using an ambulatory electronic medical
      record in an HMO.
AB  - The Northwest Region of Kaiser Permanente implemented a comprehensive clinical
      information system in two sites between February and December 1994. By year end
      46 primary care clinicians and 95 supporting personnel used the system on a daily
      basis to provide patient care. Clinicians use the product to select coded
      diagnoses, and directly order laboratory, imaging, and other tests, internal
      referrals, and prescriptions. They enter progress notes into the system, and use
      it to generate patient focused visit summaries. Clinicians took approximately 2
      minutes longer, on average, to complete patient visits post-implementation. Most
      of this time was spent performing "orders and diagnosis" work, which included new
      required elements in the post-implementation period. Clinicians worked
      approximately 30 days before reaching their baseline visit rate and "lost"
      approximately 48 hours of productivity during the learning, including classroom
      training. User acceptance improved from 2 to 4 months of use.

PMID- 8563381
TI  - Evaluating the impact of structured text and templates in ambulatory nursing.
AB  - This evaluation looks at the use of templates for entering structured text
      nursing notes that generate both a legal text note that is the chart record and
      an underlying coded form of the note to support analysis and research. This study
      reflects the first phase of a prototype project of an integrated, computerized
      health record. Templates are notes that have been prewritten using a standard
      clinical vocabulary. Templates can be used as the basis of a new clinical note
      and can be either signed unchanged or modified to represent variations in
      clinical presentation. The prototype setting is a Primary Care clinic where both
      physicians and nurses are using the computer to enter clinical notes. In the
      prototype clinic team, nursing utilized the CPR for 100% of all documentation
      from day one. Use of templates was found to be the most frequent method of
      initiating a note.

PMID- 8563382
TI  - Evaluating a comprehensive outpatient clinical information system: a case study
      and model for system evaluation.
AB  - Decisions about information system implementation are often justified through a
      cost-benefit analysis. The ability to improve efficiency and outcomes while
      decreasing costs through information systems--by allowing for multiple and
      instant simultaneous access to information, through data monitoring and altering,
      through automation of protocols, and by collecting information for population
      based health care as opposed to individual illness-care--are all potential
      benefits of a comprehensive clinical information system. Measuring the
      quantitative impact of these system improvements, however, is difficult. Doing a
      complete cost-benefit analysis of a comprehensive clinical information system is
      unrealistic due to the many assumptions necessary and the multiple confounding
      factors that are involved. In our Clinical Information Systems deployment in
      Kaiser Permanente, Northwest Region, we have elected not to do a detailed cost
      benefit analysis. Instead, we have done an evaluation, based on success criteria,
      of a pilot implementation of a vendor-supplied system. This evaluation is based
      on clinician acceptance, system usage, technical factors, and quantitative
      effects on physician productivity. We also considered qualitative factors such as
      relationship with and responsiveness of the system vendor. We are moving ahead to
      regionalize this clinical information system based on such an evaluation of our
      pilot project. This paper outlines the approach that we have taken in evaluating
      our implementation of this system. It may provide some guidance for organizations
      on how to make a decision about whether or not to regionalize a clinical
      information system based on the evaluation of a pilot-site implementation.

PMID- 8563383
TI  - A probability database for decision-analytic models of coronary revascularization
      procedures.
AB  - The time required to extract probabilities from medical literature is a primary
      reason decision analysis is not used more frequently for individual patient
      management decisions. Objective clinical trial information from the medical
      literature for one management decision was placed in a database which provided
      probabilities when queried. The database was tested with decision-analytic models
      of specific patient cases from the medical literature. Performance was assessed
      in terms of the ability to select trials which resembled the patients' individual
      characteristics, the number of trials providing probabilities for a given
      outcome, and the number of follow-up points available for that outcome. The
      timely assistance the database provides in expediting literature review and
      synthesis could enable the more common use of decision analysis in management
      decisions for individual patients.

PMID- 8563384
TI  - Overcoming the limitations of proprietary computerized billing systems to enhance
      patient care.
AB  - Most physician offices have proprietary computerized billing systems, but these
      are not designed for monitoring utilization or addressing patient care issues,
      and they are difficult or impossible to modify. These systems do, however,
      contain valuable diagnosis and demographic information. An open-ended, relational
      x-base system is described that downloads this billing information and combines
      it with additional input to provide the practitioner with: current problem lists;
      medication and allergy lists; health screening reminders that are age, sex and
      disease specific; and commonly used demographic information. Several popular
      query/reporting tools are used to generate standard reports and ad hoc inquiries
      that relate directly to patient care. Two studies, one involving alerting
      physicians to possible adverse medication effects on specific patients, and one
      investigating appropriate use and billing of stool occult blood testing are
      summarized. In the constantly evolving arenas of utilization, outcomes research
      and cost efficiency, such an open ended, time efficient system has unlimited
      potential to improve patient care.

PMID- 8563385
TI  - Factors impacting the success of computerized preadmission screening.
AB  - Many approaches to controlling costs under managed care rely on the ability to
      prospectively identify the type or level of service a patient requires at the
      time of presentation. Although computers may effectively predict these factors,
      the impact of such a computer system is greatly dependent on its integration into
      the admission process. Three factors that influence the effectiveness of
      predictive screening using a computer were identified. They are detection,
      intervention and compliance. The effect of these factors was then measured in a
      prospective randomized trial evaluating the effectiveness of computerized
      preadmission screening for predicting the appropriateness of inpatient care. This
      paper examines the three factors and their impact on the effectiveness of the
      system. A mathematical model that relates the factors to the overall
      effectiveness of computerized preadmission screening is proposed and considered
      in a more general context.

PMID- 8563386
TI  - Structured knowledge representation: an improved methodology for communication of
      hospital policy.
AB  - The optimal operational integrity of a health care facility depends upon the
      correct interpretation of an adherence to well designed and written policies.
      Memos describing policy and procedures can be ambiguous, hindering their
      comprehension rather than helping it. Two alternative methods have been developed
      for communicating policy: the algorithmic flow chart and a computer decision
      support program. To determine the best means of communicating policy, the written
      memo, flow chart, and computer program were compared in scenario presentation
      interviews. The average time required to complete the test scenarios was five
      minutes for the traditional memo, two minutes for the algorithm, and two minutes
      for the computer program. Accuracy improves markedly from the traditional memo to
      the computer program. ANOVA reveals that the flow chart and computer program are
      significantly superior to memos as methods for communicating hospital policy.

PMID- 8563387
TI  - A comparison of two computer-based prognostic systems for AIDS.
AB  - We compare the performances of a Cox model and a neural network model that are
      used as prognostic tools for a cohort of people living with AIDS. We modeled
      disease progression for patients who had AIDS (according to the 1993 CDC
      definition) in a cohort of 588 patients in California, using data from the ATHOS
      project. We divided the study population into 10 training and 10 test sets and
      evaluated the prognostic accuracy of a Cox proportional hazards model and of a
      neural network model by determining the number of predicted deaths, the
      sensitivities, specificities, positive predictive values, and negative predictive
      values for intervals of one year following the diagnosis of AIDS. For the Cox
      model, we further tested the agreement between a series of binary observations,
      representing death in one, two, and three years, and a set of estimates which
      define the probability of survival for those intervals. Both models were able to
      provide accurate numbers on how many patients were likely to die at each
      interval, and reasonable individualized estimates for the two- and three-year
      survival of a given patient, but failed to provide reliable predictions for the
      first year after diagnosis. There was no evidence that the Cox model performed
      better than did the neural network model or vice-versa, but the former method had
      the advantage of providing some insight on which variables were most influential
      for prognosis. Nevertheless, it is likely that the assumptions required by the
      Cox model may not be satisfied in all data sets, justifying the use of neural
      networks in certain cases.

PMID- 8563388
TI  - Iliad and Medical HouseCall: evaluating the impact of common sense knowledge on
      the diagnostic accuracy of a medical expert system.
AB  - Diagnostic expert systems are gaining acceptance among physicians. Recently, a
      comparative study of the performance of four major commercial diagnostic programs
      demonstrated that the information they produce contains a certain amount of
      irrelevancy that the trained physician ignores. Medical HouseCall is a consumer
      health information expert system based on a medical expert system for physicians,
      Iliad. To enhance the usefulness of Medical HouseCall to health care consumers,
      we are interested in significantly reducing the amount of irrelevancy contained
      in the diagnostic differential list. Testing with over 470 'textbook' cases
      revealed that a large part of the irrelevancy can be eliminated by adding
      universal and medical 'common sense' knowledge. Using four performance measures,
      we compared, on a subset of cases, the differential lists from two versions of
      the program: the refined knowledge base (1995) and an older version (1994) 'pre
      common sense'. The results suggest that the performance of a diagnostic expert
      system can be significantly improved with the addition of common sense knowledge.

PMID- 8563389
TI  - Problems with integrating legacy systems.
AB  - The economic and organizational impact of imposing state-of-the-art technology to
      the large number of proprietary legacy systems operational in most hospitals
      requires integrated clinical professional workstations to provide flexible
      encapsulation mechanisms for these systems rather than reengineering these
      systems to this new technology. In this paper the implications of different
      input/output and translation models of legacy systems for their integration into
      a clinical workstation is described. Examples of legacy systems that have been
      integrated in the HERMES clinical workstation are presented as examples of the
      range of difficulties one might encounter. The features that an integrated
      workstation should offer for integrating a broad range of legacy systems are also
      addressed in this paper.

PMID- 8563390
TI  - The evolution of a scalable departmental real-time clinical information system.
AB  - On-line Clinical Information Systems have to be both very responsive and capable
      of accessing large volumes of historic data. The EmStat Emergency Department
      Clinical Information System has evolved through several approaches to meeting
      these needs, including effective use of client/server technology, and optimizing
      all available machine resources. Currently the system is quite successful in this
      regard but the evolution continues.

PMID- 8563391
TI  - The role of the information architect at King Faisal Specialist Hospital and
      Research Centre.
AB  - Successful implementation of integrated clinical information system requires
      modification of the institution's long range strategic plans and its personnel's
      behavior. The changes warrant a concerted effort on the part of many different
      individuals; this paper describes the role of the Information Architect whose
      primary functions are to steer the process to fulfill stated objectives and build
      consensus where divergent forces are at work. The workings of the Architect is
      presented in context of a unique Middle-Eastern institution currently undergoing
      automation of clinical information.

PMID- 8563392
TI  - Real time monitoring in the control theory paradigm.
AB  - Monitoring patients hospitalized in hemato-oncology departments to undergo
      clinical protocols of therapy is a complex task. The main difficulty arises in
      the follow-up of the oncology protocol and in the management of critical episodes
      of acute illness which frequently occur due to the high toxicity of the
      antimitotics used. This problem can be conceptualized within the control theory
      paradigm as the task of controlling a process whose state can deviate
      unacceptably from a normal range. Following the control theory analogy at the
      level of knowledge bases design, we have modeled the medical knowledge as control
      information to represent the medical actions, and state information is used as a
      feedback control to readjust the command.

PMID- 8563393
TI  - Strategic exploration and analysis using interactive visualization of health care
      databases.
AB  - Effective analysis of health care information is a central component in
      formulating strategies for improvement initiatives. These initiatives involve the
      analysis of episodes of care, quality measure comparisons, resource utilization,
      and investigation of temporal relationships between various factors and outcomes.
      The ability to efficiently recognize the principal patterns and their variations
      presents special challenges. This paper describes the design issues and
      application of the Interactive Visual-Exploratory Data Analysis (IV/EDA) system.
      IV/EDA is a graphical approach to exploratory analysis of health care information
      designed to rapidly find and communicate relationships essential to formulating
      and evaluating strategies that address health care improvement.

PMID- 8563394
TI  - Patient precautions: a forgotten piece of the electronic patient record.
AB  - We define "patient precautions" as a unique group of data that is an essential
      component of the electronic patient record. Patient precautions include
      medication allergies, difficult airway precautions, infection control
      precautions, and advance directives. Any piece of data that is associated with
      the patient, can affect the management of his or her care, and is relatively
      static over time (as compared with the patient's medication list and problem
      list) can be considered a patient precaution. An important property of
      precautions is that the relevant aspects may be brought to the user's attention
      at the time a patient care decision must be made. We believe this class of data
      elements is a unique and important component of the electronic patient record
      that makes it more valuable than the paper record.

PMID- 8563395
TI  - The deployment of a World Wide Web (W3) based medical information system.
AB  - The development of Web technologies has revolutionized information dissemination
      on the Internet. The University of Minnesota Hospital and Clinic's Web Clinical
      Information System (CIS) demonstrates the use of the Web as an infrastructure for
      deploying a medical information system at a fraction of the developmental cost of
      more traditional client server systems. This Web CIS has been deployed since
      December 1994. It makes available laboratory results, including a radically
      improved clinical microbiology reporting system, ad hoc laboratory order entry,
      and an embedded expert system protocol laboratory ordering system. It provides
      these services to any physician or patient care area with TCP (or SLIP/PPP)
      connection to our hospital network backbone, whether the client computer is
      running MS Windows, the Macintosh OS, or X-Windows. A formal evaluation of one of
      this systems subcomponents, the display of clinical microbiology information,
      demonstrated a significant savings in clinician time (43% p < .001) and
      substantial reduction in interpretive errors (0 vs 15 p < .01).

PMID- 8563396
TI  - A client/server approach to telemedicine.
AB  - This paper describes the Medical College of Ohio's efforts in developing a
      client/server telemedicine system. Telemedicine vastly improves the ability of a
      medical center physician or specialist to interactively consult with a physician
      at a remote health care facility. The patient receives attention more quickly, he
      and his family do not need to travel long distances to obtain specialists'
      services, and the primary care physician can be involved in diagnosis and
      developing a treatment program [1, 2]. Telemedicine consultations are designed to
      improve access to health services in underserved urban and rural communities and
      reduce isolation of rural practitioners [3].

PMID- 8563397
TI  - Cost effective Internet access and video conferencing for a community cancer
      network.
AB  - Utilizing the ubiquitous personal computer as a platform, and Integrated Services
      Digital Network (ISDN) communications, cost effective medical information access
      and consultation can be provided for physicians at geographically remote sites.
      Two modes of access are provided: information retrieval via the Internet, and
      medical consultation video conferencing. Internet access provides general medical
      information such as current treatment options, literature citations, and active
      clinical trials. During video consultations, radiographic and pathology images,
      and medical text reports (e.g., history and physical, pathology, radiology,
      clinical laboratory reports), may be viewed and simultaneously annotated by
      either video conference participant. Both information access modes have been
      employed by physicians at community hospitals which are members of the Jefferson
      Cancer Network, and oncologists at Thomas Jefferson University Hospital. This
      project has demonstrated the potential cost effectiveness and benefits of this
      technology.

PMID- 8563398
TI  - Strategic planning for information management: what are the deliverables?
AB  - This paper describes the deliverables framework developed by Vanderbilt
      University Medical Center (VUMC) in its IAIMS planning process. The key
      deliverables include: visions for the future; mission, goals, and objectives for
      the information management function; critical functions for IAIMS; categorized
      projects; priority recommendations; and a straw man project sequence reflecting
      dependencies. The paper also discusses how the plan will be used and how it
      interacts with direction-setting for the Medical Center.

PMID- 8563399
TI  - Successful implementation of an integrated physician order entry application: a
      systems perspective.
AB  - Direct physician order entry is required for effective implementation of an
      integrated electronic medical record. This effort involves multi-level changes in
      the whole system of care, from physicians attitudes to interdepartmental
      relations. This study reports the findings of a follow-up study that quantified
      dimensions associated with successful implementation identified in a previous
      study. Results identified several implementation strategies associated with
      success. These include an interdisciplinary implementation group, involvement of
      large numbers of regular staff, early and intensive training and support, and 24
      hour available assistance as important to success. In addition, attitudes of
      physicians and their level of involvement were found to be associated with
      success.

PMID- 8563400
TI  - Cross-site study of the implementation of information technology innovations in
      health sciences centers.
AB  - An interpretive oral history technique was used to identify factors most
      important in the implementation stage of information technology innovation
      diffusion. Electronic mail, end user literature searching, and aspects of the
      computer-based patient record were the innovations selected for study at academic
      health sciences centers. Transcripts of thirty-four interviews with key
      individuals were analyzed to determine six categories of factors. Word counts
      were then used to determine underlying emphases. Analysis of variance tested
      whether there were significant differences in uses of words by categories of
      individuals, by those at different institutions, and when different innovations
      were described. Results indicate that the innovations themselves correlate
      significantly with different word categories, where category of individual and
      institution do not. Words related to the computer based patient record
      characterize further critical factors in implementing that particular innovation.

PMID- 8563401
TI  - Participatory design of computer-supported organizational learning in health
      care: methods and experiences.
AB  - This paper outlines a Computer-Supported Co-operative Work (CSCW) system for
      primary care and presents from its participatory design process time consumption,
      costs, and experiences. The system integrates a hypermedia environment, a
      computerized patient record, and an electronicmessage system. It is developed to
      coordinate organizational learning in primary care from micro to macro levels by
      connecting strategic planning to monitoring of patient routines. Summing up
      design experiences, critical issues for making CSCW systems support cost
      effectiveness of health care are discussed.

PMID- 8563402
TI  - Assessing the behavioral impact of a diagnostic decision support system.
AB  - This paper describes a prototype for research to evaluate the impact of
      diagnostic decision support systems on the behavior of physicians. Several
      indices that can be used to quantify the magnitude of impact are proposed. A
      large medical diagnostic knowledge base in internal medicine (the Iliad knowledge
      base) was used in this evaluation. The impact on behavior when different
      inference models are run against this knowledge base is evaluated for two
      different case domains and physician's specialties.

PMID- 8563403
TI  - Cat 6 mo increases symptoms: online physician charting and more.
AB  - The physicians of the Children's Asthma Center and the computer scientists of
      Information Services at Texas Children's Hospital set out to design a system that
      is comfortable to use, structured enough to effectively measure outcomes, yet
      flexible enough to conserve the individuality of the patient. To achieve these
      goals, we examined how the differential diagnosis process is applied to clinical
      decision making and implemented it in a clinical workstation. Unique patterns
      representing the state of the patient's disease are formed by dynamically
      selecting pertinent sets of observations, assigning attributes to these
      observations, and describing relationships between observations and/or sets of
      observations.

PMID- 8563404
TI  - Cost effective computerized decision support: tracking caregiver acceptance at
      the point of care.
AB  - We implemented a computerized decision support tool to standardize the
      administration of supplemental oxygen (O2) therapy in the acute care (non-ICU)
      hospital setting. Caregiver acceptance of the computerizeds oxygen therapy
      protocol (COTP) instructions was measured to determine the clinical performance
      of the computerized decision support tool. 49.6% of instructions generated were
      followed by the clinical caregiver, and 16.8% of instructions generated were
      explicitly acknowledged by the user through the COTP computer interface. Despite
      this low caregiver response rate, significant favorable changes in the
      administration of oxygen were observed. This paper is focused on the issues of
      general importance the caregiver response rate raises for the implementation and
      clinical use of computerized decision support tools, including: (1) limitations
      of the user interface and (2) inherent difficulty in changing long-standing
      practice patterns.

PMID- 8563405
TI  - Cost-effective clinical uses of wide-area networks: electronic mail as
      telemedicine.
AB  - Electronic mail (E-mail) is widely used as a means of communication in the
      medical community. E-mail is clearly inexpensive when compared to two-way, fully
      interactive, real-time, video telemedicine. By content analysis of 200
      consecutive messages, we show E-mail to be a low-cost use of computer networks,
      supporting a wide range of physician decision-making.

PMID- 8563406
TI  - Outcomes research using the electronic patient record: Beth Israel Hospital's
      experience with anticoagulation.
AB  - Using data captured as part of the routine care of outpatients taking the oral
      anticoagulant warfarin, we described variation in recording reasons for
      anticoagulation, selecting target International Normalized Ratio (INR) ranges,
      and performing coagulation blood tests. Laboratory results were directly captured
      by or entered into an Anticoagulation Flowsheet, a computer program which is
      fully integrated with our Online Medical Record (OMR). We studied the 177
      patients with flowsheets between October 1993 and January 1995. 90% had a reason
      for anticoagulation entered; 29 different target INR ranges were entered. For
      patients with a target INR of 2.0-3.0, the mean number of weeks between blood
      tests, after a test which was in range, was three weeks (standard deviation 1.7
      weeks, range one to twelve weeks). We conclude that routinely collected data
      contained in an electronic patient record (EPR) can be a rich resource for
      describing and evaluating clinical practice. We also address several limitations
      to using EPR data: validity of EPR information, lack of coded information, and
      imperfect capture of clinician thought processes.

PMID- 8563407
TI  - Computers in the examining room: the patient's perspective.
AB  - CompuHx* is an Interactive Health Appraisal System (IHAPS) used in the examining
      room at Kaiser-Permanente's San Diego Department of Preventive Medicine to record
      patient information, assist in diagnosis, and provide a legible summary of
      findings. The purpose of the present project was to examine the impact of
      computer use in the examining room on patient satisfaction with the Health
      Appraisal experience. Survey results showed no significant differences in patient
      satisfaction between patients whose examiners used CompuHx and those whose
      examiners did not. These findings indicate that, in the eyes of the patients
      surveyed, clinician use of a computer in the examining room did not depersonalize
      their relationship with the clinician, nor did it enhance satisfaction with the
      thoroughness of the exam or confidence in the examiner's findings.

PMID- 8563408
TI  - HealthDesk for Hemophilia: an interactive computer and communications system for
      chronic illness self-management.
AB  - HealthDesk for Hemophilia is an interactive computer software application
      designed on the premise that successful chronic illness self-management requires
      information, self-care skills, on-going communication with health care providers,
      and user-friendly record keeping. The software was pilot tested for six months in
      the homes of eight hemophilia patients. The purpose of the pilot was to assess
      the impact of HealthDesk for Hemophilia on patient satisfaction, patient-provider
      communication, and user confidence in chronic illness self-management. Results
      from the pilot show that when HealthDesk for Hemophilia is made available to
      patients and their families, they use it, value it, and gain confidence in their
      illness self-management skills. Users also report high satisfaction with their
      health care providers.

PMID- 8563409
TI  - Clinical results using informatics to evaluate hereditary cancer risk.
AB  - A 12-year medical informatics project is described whose goal was to create a
      distributable computer-based service to support the identification of hereditary
      cancer patterns and recommend concomitant protocols of patient care surveillance.
      Key elements of the successful implementation strategy are described as the
      service has been successfully utilized at more than a dozen other cancer centers.
      Multi-year clinical results are presented from the implementation of this
      service.

PMID- 8563410
TI  - Using a pen-based computer to collect health-related quality of life and
      utilities information.
AB  - We have developed a system that uses the Newton MessagePad technology as part of
      a client-client-server paradigm to collect health-related quality of life
      information from breast cancer patients attending an outpatient clinic at the
      Dana-Farber Cancer Institute. Patients are asked to fill out an electronic
      questionnaire on the Newton, which then uploads the information into the
      institution's Oracle database. The program consists of a separate questionnaire
      engine and question base, facilitating questionnaire design and allowing us to
      give different questionnaires to different patients dynamically. The results of a
      preliminary trial show excellent user-acceptance of the device. Finally, we
      present a general framework for such systems and discuss issues that developers
      must consider when implementing a pen-based computer project.

PMID- 8563411
TI  - Retrieving research studies: a comparison of bibliographic and full-text versions
      of the New England Journal of Medicine.
AB  - It has been established that subject searches of medical full-text databases
      obtain higher recall than subject searches in a bibliographic database. In this
      study we attempted to determine if the same rule might apply when searching for a
      non-subject parameter such as study design. A simultaneous search of
      bibliographic and full-text records from the New England Journal of Medicine
      provided data on the number of items retrieved by each kind of search. Filtering
      strategies were created for 5 different study types: randomized controlled
      trials, other clinical trials and prospective studies, cohort studies,
      longitudinal and follow-up studies, and multicenter studies. The point of the
      study was to compare the numbers of items retrieved from the bibliographic
      database, MEDLINE, and those retrieved from the full-text version of NEJM, and to
      examine the unique access points available in each file. For all the study types
      the full-text file retrieved a larger number of records than MEDLINE, most of
      which were retrieved because of methodology terms found in the text but not in
      the title or abstract. In MEDLINE, descriptors and publication types, two value
      added fields supplied by indexers, retrieved 11-89% more than title and abstract
      alone.

PMID- 8563413
TI  - The SAPHIRE server: a new algorithm and implementation.
AB  - SAPHIRE is an experimental information retrieval system implemented to test new
      approaches to automated indexing and retrieval of medical documents. Due to
      limitations in its original concept-matching algorithm, a modified algorithm has
      been implemented which allows greater flexibility in partial matching and
      different word order within concepts. With the concomitant growth in client
      server applications and the Internet in general, the new algorithm has been
      implemented as a server that can be accessed via other applications on the
      Internet.

PMID- 8563412
TI  - Contextual models of clinical publications for enhancing retrieval from full-text
      databases.
AB  - Conventional methods for retrieving information from the medical literature are
      imprecise and inefficient. Information retrieval systems employ unmanageable
      indexing vocabularies or use full-text representations that overwhelm the user
      with irrelevant information. This paper describes a document representation
      designed to improve the precision of searching in textual databases without
      significantly compromising recall. The representation augments simple text word
      representations with contextual models that reflect recurring semantic themes in
      clinical publications. Using this representation, a searcher may indicate both
      the terms of interest and the contexts in which they should occur. The contexts
      limit the potential interpretations of text words, and thus form the basis for
      more precise searching. In this paper, we discuss the shortcomings of traditional
      retrieval systems and describe our context-based representation. Improved
      retrieval performance with contextual models is illustrated by example, and a
      more extensive study is proposed. We present an evaluation of the contextual
      models as an indexing scheme, using a variation of the traditional inter-indexer
      consistency experiments, and we demonstrate that contextual indexing is
      reproducible by minimally trained physicians and medical students.

PMID- 8563414
TI  - Teleform scannable data entry: an efficient method to update a community-based
      medical record? Community care coordination network Database Group.
AB  - Community-based multi-disciplinary care of chronically ill individuals frequently
      requires the efforts of several agencies and organizations. The Community Care
      Coordination Network (CCCN) is an effort to establish a community-based clinical
      database and electronic communication system to facilitate the exchange of
      pertinent patient data among primary care, community-based and hospital-based
      providers. In developing a primary care based electronic record, a method is
      needed to update records from the field or remote sites and agencies and yet
      maintain data quality. Scannable data entry with fixed fields, optical character
      recognition and verification was compared to traditional keyboard data entry to
      determine the relative efficiency of each method in updating the CCCN database.

PMID- 8563415
TI  - A trial bank model for the publication of clinical trials.
AB  - Clinical trials constitute one of the main sources of medical knowledge, yet
      trial reports are difficult to find, read, and apply to clinical care. Reasons
      for these difficulties include the lack of a common, standardized, structure for
      trial reports; the restricted length of reports; and limited computer support for
      use of the literature. We propose a new model of reporting clinical trials, in
      which trials are published as both prose commentary and as data in electronic
      "trial banks." The prose will allow authors to discuss their trials in writing;
      the electronic database will allow readers easy access to well-defined data about
      the trials. We are developing a formal conceptual model of the clinical trials
      domain for integrating the use of multiple trial banks. We will then focus on
      validating this conceptual model with clinical literature users.

PMID- 8563416
TI  - ASN.1: defining a grammar for the UMLS knowledge sources.
AB  - The unified Medical Language System (UMLS) project provides resources on an
      experimental basis to the research community. In 1995 the four UMLS Knowledge
      Sources have been provided in an additional data format, Abstract Syntax Notation
      One (ASN.1). The benefits of ASN.1 are that it provides a standard, formal
      grammar for complex data and allows exchange of that data in a way which is
      independent of the particular software and hardware environment in which the data
      are created and stored. The paper begins with an introduction to the ASN.1
      standard itself. It continues with a discussion of the ASN.1 implementation of
      the UMLS Knowledge Sources and some of the consequences for the newly released
      UMLS Knowledge Source Server. It concludes with a discussion of some of the
      benefits of using ASN.1 encoded data.

PMID- 8563417
TI  - Enhancements of anatomical information in UMLS knowledge sources.
AB  - Although anatomical terminology forms a part of biomedical structured
      vocabularies, available sources lack the requisite granularity, semantic types
      and relationships for comprehensively and consistently representing anatomical
      concepts in machine readable form. Thoracic angiology was selected as a proof of
      concept experiment for in depth representation of symbolic information in gross
      anatomy through the enhancement of semantic types, concepts and relationships in
      UMLS. Provided the representation of concepts is comprehensive, hierarchies
      generated with four types of simple relationships are capable of displaying
      anatomical information from the systemic view point with sufficient detail to
      meet the needs of applications in basic science education and in the practice of
      surgical subspecialties.

PMID- 8563418
TI  - Categorization by reference: a novel approach to MeSH term assignment.
AB  - Categorization by Reference is a novel text classification technique that
      examines the existing classifications of the citations found in an as-yet
      unclassified text to determine what terms should be assigned to that text. The
      existence of the Medical Subject Headings and MEDLINE make the biomedical domain
      a prime candidate for application of this technique. We describe our approach and
      implementation of a prototype, presenting some results of our initial tests. We
      further discuss refinements that could improve the precision of the technique,
      and describe its possible use in categorizing portions of the World-Wide Web.

PMID- 8563419
TI  - Comparing clinical vocabularies using coding system fidelity.
AB  - Much effort has been directed toward the development of an ideal multipurpose
      controlled medical vocabulary for use in human and veterinary medicine. SNOMED
      International is one effort that has resulted in a larger and more complex
      nomenclature system. Although it was able to code more concepts, SNOMED
      International failed to statistically improve vocabulary fidelity when compared
      with the 30+ year old SNVDO vocabulary. We found that SNOMED has a lower
      intercoder consistency than SNVDO and that a greater number of codes were
      necessary to represent an individual concept. Our study shows a significant Coder
      Vocabulary interaction which suggests that more emphasis should be placed on
      coding guidelines and coder training. Clinician data entry and coding may be
      necessary for maximum vocabulary fidelity.

PMID- 8563420
TI  - Teaching literature searching in the context of the World Wide Web.
AB  - As part of the required curriculum for medical students, we devised a literature
      searching practicum that has been used for two years. In both years, we stressed
      going beyond the skills needed for using a particular searching program, towards
      a more conceptual approach to information searching. In the first year, the
      practicum was taught in a traditional lecture/hands-on format. In the second
      year, the lecture was replaced by a World Wide Web-based tutorial
      (http:@www.welch.jhu.edu/Education/tutorials/pra cticum.html). To our knowledge,
      this is the first Web-based resource intended to teach students about appropriate
      use of search technology. Comparison of student evaluations showed no difference
      in attitude toward the two versions of the practicum, and observation of student
      performance suggested similar levels of proficiency. We conclude that placing
      these educational materials on the Web (1) makes us practice what we preach; (2)
      is as effective as traditional teaching methods; and (3) gives students a
      resource for reinforcement learning.

PMID- 8563421
TI  - Automated MeSH indexing of the World-Wide Web.
AB  - To facilitate networked discovery and information retrieval in the biomedical
      domain, we have designed a system for automatic assignment of Medical Subject
      Headings to documents retrieved from the World-Wide Web. Our prototype
      implementations show significant promise. We describe our methods and discuss the
      further development of a completely automated indexing tool called the "Web-MeSH
      Medibot."

PMID- 8563422
TI  - A model of clinical query management that supports integration of biomedical
      information over the World Wide Web.
AB  - A model of clinical query management is described that supports the integration
      of various types of biomedical information and the delivery of that information
      through a common interface. The model extends the architecture of the World Wide
      Web to include a Common Gateway Interface (CGI) mediator, which takes in user
      queries, performs syntactic and semantic processing to transform the input to a
      canonical form, selects the appropriate information sources to answer the query,
      translates the canonical query statement into a query of each information
      resource, queries the chosen information sources in parallel, and controls the
      analysis and display of results. We describe WebMedline, a CGI mediator that
      implements portions of this model, and discuss the benefits and limitations of
      this approach.

PMID- 8563423
TI  - Medical information retrieval and WWW browsers at Mayo.
AB  - Medical information retrieval from "Master Sheet" entries specially indexed for
      research retrieval has been part of the Mayo culture since 1909. Providing easy
      to use and universally available WWW access to these and other patient
      information databases at Mayo via browsers, shines a bright light on issues of
      privacy and confidentiality, user authentication, need to know, data transmission
      security, and technical details of interfacing disparate databases on a spectrum
      of platforms to many types of workstations using a variety of browsers. We review
      our recent experience, and generalize pertinent issues.

PMID- 8563424
TI  - Design considerations for intelligent data entry: development of MedIO.
AB  - Capturing clinical data is a multi-faceted problem. This paper discusses clinical
      data entry problems encountered during the development of an intelligent clinical
      data entry system. Based on a review of the problems, recommendations are made
      for an approach to the design of clinical data entry programs. These
      recommendations include a discussion of key components in the design process as
      illustrated by the development of MedIO, a C++ computer program for the entry of
      history and physical exam information.

PMID- 8563425
TI  - Intelligent monitor for an anesthesia breathing circuit.
AB  - A competent breathing circuit is mandatory to the safe and effective delivery of
      oxygen and anesthetic gases to the patient. Studies have shown that failures in
      the circuit are the most likely causes of anesthetic mishaps. Unfortunately, the
      complexity of the system renders traditional monitoring methods ineffective. We
      have developed a hierarchical artificial neural network monitor that is capable
      of examining ventilator signals. It was trained to identify 23 faults in the
      breathing circuit during ventilator controlled breathing and 21 faults during
      spontaneous breathing. The networks correctly identified a fault condition in 92%
      and 83% of cases for ventilator and spontaneous data, respectively. The correct
      fault type was found in 76% and 68% of cases for ventilator and spontaneous data,
      respectively. Results show that the network met our criteria for a holistic,
      specific, and vigilant monitoring system.

PMID- 8563426
TI  - [Cryotherapy of malignant eyelid tumors].
AB  - The treatment of tumors of the eyelids must extend not only to complete removal
      or destruction of the neoplasm, but also to the maintenance of physiology
      functions. In addition, cosmetic aspects should be taken into consideration. In a
      prospective study, 278 cryosurgical operations performed for lid tumors in the
      years from 1980 to 1985 were followed up for 5 years to decide whether
      cryotherapy fulfilled these demands. We used spray freezing with liquid nitrogen,
      because the low temperatures and high freezing rates required for cell
      destruction are achieved only by this technique. The 5-year recurrence rate was
      3.5%. The liquid nitrogen therapy is especially suitable when the eye lids are
      operated on, because the lacrimal system remains functional. Gas expansion
      cryotherapy should not be used in in the treatment of tumors, as it may lead to
      stimulation of growth.

PMID- 8563427
TI  - [Coagulase-negative staphylococci in normal and chronically inflamed
      conjunctiva].
AB  - This study examines the prevalence of coagulase-negative Staphylococcus species
      in normal and mildly inflamed conjunctiva, their sensitivity to antibiotics, and
      their relationship to the remaining flora. PATIENTS AND METHODS: In 99 patients
      including 9 HIV-positives in an early stage of the infection, 100 conjunctival
      swabs were taken and microbiologically investigated for bacteria and fungi.
      Thirty-four were from healthy eyes. 40 were from patients with chronic (n = 28)
      and unspecific (n = 12) conjunctivitis, 17 were from patients with a variety of
      outer inflammatory ocular conditions, and 9 were from the HIV group from
      uninfected (n = 6) and infected (n = 3) conjunctivae. Samples from each patient
      were collected with three moistened cotton swabs and directly inoculated onto
      five different agars, followed by immersion into three specific culture broths.
      Staphylococci were identified species-wise, the other microorganisms genus-wise.
      Sensitivity to a broad spectrum of antibiotics was determined by agar diffusion
      tests. OUTCOME: Staphylococci were found in 89%, which was the highest prevalence
      genus-wise. Of those, coagulase-negative species accounted for 86%, while
      coagulase-positive Staphylococcus aureus was isolated in 12% of all swabs. In the
      86 smears positive for coagulase-negative staphylococci, 151 different strains
      were isolated. In these strains, resistance to the 13 tested antibiotics varied
      from 0% for vancomycin to 66% for penicillin. Strains which were isolated from
      patients with chronic conjunctivitis showed a greater range of resistance than
      those from normal flora, with significant levels for ciprofloxacin, gentamycin
      and kanamycin (Mann-Whitney) U-test: P < 0.05). All except six strains of
      staphylococci were identified strains represented ten species, of which
      Staphylococcus epidermidis was most prevalent (74%), but only made up 70% of all
      isolated strains of the coagulase-negative staphylococci. Staphylococcus aureus
      and gram-negative bacteria were found significantly more commonly in patients
      which chronic conjunctivitis than in healthy eyes, while coagulase-negative
      species of the Micrococcaceae family were significantly more prevalent in the
      healthy than in the chronically inflamed conjunctiva (chi-square: P < 0.05).
      CONCLUSION: The conjunctiva can simultaneously host several stems of coagulase
      negative staphylococci, which differ in regard to species and resistance to
      antibiotics. This variety might indicate a microbiological balance of the
      conjunctiva and be reduced in chronic inflammatory conditions. In patients with
      chronic conjunctivitis the risk for multiresistant coagulase-negative
      staphylococci is increased.

PMID- 8563428
TI  - [Lid-parallel conjunctival folds are a sure diagnostic sign of dry eye].
AB  - Dry eye syndromes are becoming more important for the ophthalmologist. Various
      circumstances lead to a significant impairment of the three layered precorneal
      film, whose disturbed equilibrium causes diverse pathological changes in the
      ocular surface. Apart from symptoms and clinical signs, various clinical tests
      and laboratory procedures can be used to confirm the diagnosis. We looked at the
      utility of the lid-parallel conjunctival fold (LIPCOF) with regard to the
      diagnosis "dry eye". In this publication we describe and classify LIPCOF, stage 0
      to stage 3, and investigate its relationship to the severity of dry eye. Dryness
      is determined by the "sicca score", a scale between 0 and 12 based on a wide
      ranging spectrum of tests, including the Schirmer I-test, tear-film break-up
      time, rose bengal and and fluorescein staining, the lysozyme test and impression
      cytology. In this prospective study we examined one eye in each of 267 patients,
      assigning them to one of two groups based on the absence or presence of LIPCOF.
      These two groups are comparable in gender and age (group-matching). For the
      diagnosis of dry eye, using LIPCOF, statistical analysis of the data showed a
      negative predictive value of 75.95% and a positive predictive value of 93.09%.
      The correlation pattern of LIPCOF with the patient's medical history and slit
      lamp. They are a dependable diagnostic sigh of dry eye. Consideration and
      classification of LIPCOF enlarges and facilitates diagnosis of dry eye syndromes
      by the ophthalmologist.

PMID- 8563429
TI  - [Contribution of the ophthalmologist to presymptomatic diagnosis of familial
      adenomatous polyposis (FAP)].
AB  - Familial adenomatous polyposis (FAP) represents a hereditary precancerous
      condition. Symptoms often appear malignant transformation only. For persons at
      risk early recognition of gene carriers is essential. Approximately 80% of the
      patients show congenital hypertrophy of the retinal pigment epithelium (CHRPE)
      that can be recognized before clinical manifestation of FAP. In order to predict
      FAP 9 patients and 10 persons at risk from 6 FAP families were examined by
      endoscopy, molecular genetical and ophthalmological methods. Four patients from
      two families each had bilaterally 4 CHRPE; four persons at risk did not have
      CHRPE. This is in accordance with endoscopic and molecular genetic results. The
      five patients and six persons at risk from the other four families did not have
      CHRPE, i.e., the percentage of CHRPE in the FAP patients examined was only 45%.
      Funduscopy permits early identification of gene carriers in families where the
      FAP patients have CHRPE. CHRPE is not present in persons at risk in these
      families, it is not necessary to conduct invasive diagnostic measures. Funduscopy
      should always be done in FAP patients and in persons at risk from CHRPE-positive
      families. An endoscopic examination should be recommended when CHRPE is observed
      incidentally in a person with a negative family history for FAP.

PMID- 8563430
TI  - [Effect of tonometry and nasolacrimal duct irrigation on bacterial flora of the
      conjunctiva].
AB  - This study was undertaken to assess the influence of preoperative
      ophthalmological examinations on the microbial flora of the conjunctiva. For this
      purpose, 112 patients awaiting ocular surgery were included in the study.
      Conjunctival swabs for microbiological investigation were taken by nurses on the
      day of admission. In addition, specimens were taken before an ophthalmological
      examination, after applanation and impression tonometry, after irrigation of the
      lacrimal duct and 2 h after the end of all examinations. A last swab was taken
      preoperatively. Comparison of the microbiological results of the first two
      specimens only showed an agreement in 53% of the cases. The increase after
      tonometry and irrigation of the lacrimal duct in the number of swabs that were
      positive was not permanent. Swabs that were primarily germ-free and those that
      were mostly contaminated also showed strong bacterial fluctuation. Based on the
      present results, there is no strong evidence that the microorganisms found at the
      preoperative examinations correlate with a higher risk of postoperative
      infection. Disinfection of the conjunctival sac and the application of antibiotic
      drops are necessary on the day before the operation and immediately before it.

PMID- 8563431
TI  - [Erythema exsudativum multiforme major].
AB  - Erythema exudativum multiforme major (EEMM), also know as Stevens-Johnson
      syndrome, may cause severe conjunctival and corneal alterations. The etiology
      remains unknown. The aim of are study was to evaluate the clinical course,
      therapy and prognosis of ocular involvement. PATIENTS AND METHODS: In a
      retrospective study, we evaluated ten patients with EEMM who were treated between
      1986 and 1994 at the University Eye Clinic Tubingen. RESULTS: The age of the four
      female and six male patients varied between 5 and 70 years. Drugs as a possible
      precipitating factor were found in all cases (acetylsalicylicacid, sulfonamide,
      erythromycin, cotrimoxazole, Valproinicacid, paracetamol). Eight patients
      experienced an infection at the same time. Clinically, we were able to
      differentiate two groups regarding severity of the disease. Seven patients were
      characterized by ocular alterations that only involved the conjunctiva, leading
      to conjunctival scars. In those cases local treatment with antibiotics and
      corticosteroids was effective. In the second group severe ocular damage occurred,
      with symblephara, keratinization and consecutive perforating keratoplasty.
      Secondary infections became evident in a total of six cases from the two groups.
      SUMMARY: Drugs as a possible precipitating factor could be identified in all
      cases. In eight of ten patients previous infection was known. This agrees with
      literatures reports of viral infections (e.g. herpes simplex) as cofactors
      causing EEMM, especially for the aggressive form, remains unresolved. The danger
      of possible superinfection should always be taken into consideration.

PMID- 8563432
TI  - [Fluconazole level in aqueous humor after oral drug administration in humans].
AB  - For 2 years fluconazole, a triazole antimycotic, has been available for treatment
      of systemic mycosis. Compared to amphotericin B fewer severe side effects have
      been reported. So far, no data have been published as to its penetration into the
      human eye. In the present study, 20 cataract patients were given 200 mg
      fluconazole (0.5 to 8 h preoperatively. During the cataract operation 0.1 ml of
      the aqueous was removed as well as 10 ml serum. With the help of high-pressure
      liquid chromatography (HPLC), the concentration of fluconazole in each of the
      samples was determine. If the aqueous humor was removed at least 2h after
      fluconazole application, concentrations between 2.7 and 5.4 micrograms/ml were
      reached (mean 3.7 +/- 2.17) In these cases the concentration in the aqueous humor
      was 80% of the concentration found in the serum at the same time. If the sample
      of the aqueous humor was collected only 1 h after application, 40% of the
      concentration in the serum was found in the aqueous humor. These data prove that
      fluconazole shows an extremely good penetration through the blood-aqueous
      barrier. After a single dose of 200 mg, a concentration is reached in the eye
      that surmounts the minimal inhibiting concentration found for Candida species
      sensitive to fluconazole. Therefore, fluconazole seems to be a good alternative
      to amphotericin B for the treatment of infections caused by such fungi.

PMID- 8563433
TI  - [Comparison between local and systemic administration of cyclosporin A on the
      effective level in conjunctiva, aqueous humor and serum].
AB  - Cyclosporine is an important tool for the therapy of immunological diseases of
      the cornea and conjunctiva, as well as the treatment of patients with high-risk
      corneal grafts. However, potentially severe systemic side effects are
      disadvantageous. The purpose of our study was to determine if topical ocular
      application leads to about the same concentrations in ocular tissues as systemic
      application. Therefore, the concentration of cyclosporine in conjunctiva, aqueous
      humor and blood was measured by radioimmunoassay in six patients with systemic
      administration of cyclosporine and ten patients who received one drop of topical
      cyclosporine 2% four times prior to cataract surgery. All patients with systemic
      application showed measurable concentrations of cyclosporine in blood, as did
      four patients in the group receiving topical cyclosporine. There was no
      significant difference between both groups concerning cyclosporine concentration
      in aqueous humor. The level of cyclosporine in the conjunctiva was significantly
      higher after topical application (P < 0.02). In conclusion, therapy with
      cyclosporine eye drops results in levels in the conjunctiva and aqueous humor
      that are comparable to or even higher than those after systemic application if
      the last application was no more than 18h prior to the measurement. Therefore,
      topical ocular application of cyclosporine, which reduces or eliminates the
      drug's systemic side effects, can be used to induce local immunosuppressive
      activity, particularly in the treatment of superficial immunological diseases and
      after limbal allograft transplantation.

PMID- 8563434
TI  - [Selective inhibition of replication of human cytomegalovirus by desferrioxamine
      in vitro and in vivo (case report)].
AB  - In AIDS patients cytomegalovirus (HCMV) retinitis is one of the most frequent
      opportunistic infections. Antiviral therapy aims at preserving vision as long as
      possible, but more and more HCMV isolates are proving to be resistant to
      ganciclovir (GCV) and foscarnet (PFA) in vitro. We tested whether desferrioxamine
      (DFO), an iron chelator with antiherpetic activity, can inhibit clinical virus
      isolates and laboratory strains. Clinical isolates were obtained from urine
      samples of AIDS patients with HCMV retinitis. The concentrations of DFO required
      for 50% and 90% reduction of the production of HCMV in several HCMV strains
      ranged from 3.1 to 4.9 microns and from 14.2 to 17.3 microns, respectively,
      Inhibitory effects of DFO on HCMV replication were completely prevented by co
      incubation with stoichiometric amounts of FE3+. CASE REPORTS: DFO was
      administered by daily dose of 1 g i.v. to a patient with AIDS in whom HCMV
      retinitis continued to progress despite combination therapy with GCV and PFA. The
      addition of DFO to the combination inhibited progression of the disease. No
      relapse of HCMV retinitis was seen with 3 months of DFO therapy. The treatment
      was free of side effects.

PMID- 8563435
TI  - [Ultrasound biomicroscopy for evaluation of space-occupying lesions of the
      anterior eye segment. Initial results].
AB  - Pavlin's group developed the ultrasound biomicroscope, and it has been in use
      since 1990. It is an ultrasound method working at high frequencies between 40 and
      100 MHz. It is possible to resolve structures up to approximately 50 microns in
      size at a maximal depth of 5 mm. We examined about 80 patients with tumors in the
      anterior segments of the eye, mainly in the iris and the ciliary body. Good
      differentiation between cystic and solid space-occupying lesions is possible to
      say whether or not is malignant.

PMID- 8563436
TI  - [Effect of non-steroidal anti-inflammatory drugs on inflammatory reaction. An
      animal experiment study].
AB  - Previous investigations indicate that the application of a cyclooxygenase
      inhibitor alone can lead to amplification of the inflammatory process. To prevent
      this response a combination of flurbiprofen and leukotriene receptor antagonist
      (S 872419 A, Hoechst AG, Frankfurt/Main) were tested in an animal model. The
      right eye of 48 rabbits was burned with alcali (0.25 mol/l sodium hydroxide).
      Thirty animals were treated with (0.03% flurbiprofen sodium eye drops and 1%
      S872419 A eye drops, five times daily). Eighteen animals received no therapy for
      up to 14 days. Hyperemia of the limbal vessels, corneal vascularization, the
      number of PMNLs in the cornea and the prostacyclin level in the anterior chamber
      of the eye (ELISA) served as criteria. On day 3, after the chemical burn only the
      therapy group showed a significant decrease in hyperemia of the limbal vessels
      (14th day: score with therapy 0.3, without 2.17, P < 0.05). Without therapy
      corneal vascularization filled a much larger area from the 6th day on (14th day:
      area with therapy 3.5 mm2, without 63.7 mm2, P < 0.05). The number of PMNLs was
      effectively limited by therapy in the superficial stromal layers of the cornea
      and with therapy showed 2.4 cells/0.014 mm2 and without 18 cells/0.014 mm2 after
      48 h. Without Therapy the level of prostacyclin was up to 15 times higher than
      with (12-h value with therapy) 607 pg/ml, without 9094 pg/ml, P < 0.05).
      Suppression of cyclo- and lipoxygenase-mediated inflammatory responses is
      possible with the combination of flurbiprofen and S 872419 A when two arachidonic
      by inhibition of prostanoid synthesis and leukotriene receptor block at the same
      time.

PMID- 8563437
TI  - [Severe eye involvement in pemphigus vulgaris].
AB  - Pemphigus vulgaris (PV) is an immune-mediated vesiculobullous disease of the skin
      and mucous membranes. Generally, patients with PV present first with oral
      lesions, which may precede the cutaneous lesions, such as bullae and erosions, by
      several months. An ocular manifestation is unusual. The most common
      ophthalmologic involvement in pemphigus is conjunctivitis, but without
      progressive scarring such as occurs in ocular cictricial pemphigoid. Corneal
      involvement is very rare. CASE REPORT. We report on severe ocular involvement in
      a 56-year-old male Turkish patient with PV. Ophthalmologic findings included
      conjunctival cicatrization, corneal ulceration and corneal perforation, despite
      immunosuppressive therapy with azathioprine and corticosteroids. A penetrating
      keratoplasty was performed, but rapidly failed because of corneal
      vascularization. CONCLUSION. If a chronic bullous dermatosis leads to severe eye
      involvement, PV should be considered in the differential diagnosis besides ocular
      cicatricial pemphigoid. Pemphigus vulgaris can be differentiated on the basis of
      clinical findings and histopathological and immunohistological features.
      Generally, PV can be treated with steroids or with a combination of an
      immunosuppressant and steroids. However, the combination of prednisone and
      azathioprine could not prevent corneal perforation in our patient.

PMID- 8563438
TI  - [Argon laser coagulation of xanthelasmas].
AB  - For the therapy of palpebral xanthelasmas surgical, chemical and physical methods
      are used. We report on the first results of argon laser coagulation of 32
      xanthelasma lesions with an average size of 34 mm2 in 11 women and 2 men. The
      lesions were treated with argon green, spot size 1000 microns, energy 250-500 mW
      and continuous mode. The therapy was well tolerated; all lesions responded to the
      therapy. There were no complications, and no functionally relevant scars
      developed. The cosmetic outcome was assessed as good or very good in 80%). Twelve
      recurrences were seen after 12-16 months. The method described represents an
      alternative treatment in selected cases. It is easy to perform and very well
      accepted by the patients.

PMID- 8563439
TI  - [Reproducibility of measurements with the Heidelberg retina tomograph in fundus
      elevations].
AB  - PURPOSE: The Heidelberg Retina Tomograph (HRT) was intended to evaluate the optic
      nerve head. It is, however, also possible to measure retinal elevations. There
      are no systemic data on the reproducibility of HRT measurements of retinal
      elevations. We now provide such data. METHODS: 117 measurements in patients with
      diseases which are characterized by retinal elevations were analyzed with the
      HRT. We measured the "volume above surface" of the retinal elevations. Each
      patient was analyzed three times, and the coefficient of variation was
      calculated. RESULTS: The coefficient of variation was between 0.55% and 40.5%.
      Some 42% of the coefficients of variation were between 0% and 10%, 31% between 5%
      and 10%, 21% between 10% and 20%, and 6% larger than 20%. CONCLUSION: The
      reproducibility of the HRT measurements in retinal elevations is clinically
      sufficient. The relation between sufficient reproducibility and accuracy is
      discussed.

PMID- 8563440
TI  - [Ruthenium 105-applicator for radiation treatment of carcinoma in situ of the
      cornea and conjunctiva].
AB  - Intraepithelial neoplasias of cornea and conjunctiva are rare epibulbar tumors.
      In this report we describe the cases of two male patients, aged 37 and 80 years,
      each with histologically confirmed carcinoma in situ of the cornea and
      conjunctiva affecting one eye. Both carcinomas recurred in spite of complete
      surgical excision of the tumor. One patient had additional cryotherapy. Both
      recurrences were treated once with radiotherapy using a conventional 106Ru
      applicator. The applicator was fixed to the sclera adjacent to the corneal
      limbus. A 100 Gy radiation dose was delivered with 2mm tissue penetration. No
      complications were observed post-operatively. The 2-year follow-up examinations
      showed no further recurrences. Brachytherapy with 106 Ru applicator was thus
      effective in achieving local tumor control. These findings suggest brachytherapy
      of the anterior segment using the 106 Ru applicator as the first-line procedure
      in the early stages of epithelia dysplasia or carcinoma in situ.

PMID- 8563441
TI  - Inflammatory pseudotumor of the anterior orbit. A symptom in allergic
      granulomatous angiitis (Churg-Strauss syndrome).
AB  - Allergic granulomatosis accompanied by angiitis (Churg-Strauss syndrome)
      constitutes an unusual disorder which is characterized clinically by bronchial
      asthma and hypereosinophilia, accompanied by systemic symptoms of
      histopathologically and by necrotizing vasculitis, extravascular granulomas and
      tissue infiltration by eosinophils. We report a case of a 4 year-old child
      presenting with acute pneumonia and deteriorated general condition. The biopsy of
      an inflammatory pseudotumor of the right anterior orbit revealed necrotizing
      vasculitis, extravascular epitheloid granuloma and eosinophilic tissue
      infiltration. These are characteristic changes of allergic granulomatous
      vasculitis (Churg-Strauss syndrome. Laboratory findings were characterized by
      blood eosinophilia, increased IgE value and the presence of antineutrophil
      cytoplasmic ant antibodies (p-ANCA). Local and systemic manifestations quickly
      regressed after parenteral application of corticosteroids. Two exacerbations of
      inflammatory pseudotumor occurred after reduction of the corticosteroid dosage.
      Systemic vasculitic syndromes are rare in childhood. Orbital manifestations in
      Churg-Strauss syndrome in childhood have never been reported.

PMID- 8563442
TI  - [Mechanically-induced eye movement disorders].

PMID- 8563443
TI  - Outcome of head injury in 2298 patients treated in a single clinic during a 21
      year period.
AB  - Between 1968 and 1988, 2298 head-injured patients of all grades of severity were
      registered in the data bank of a single clinic. The majority of patients were
      admitted to a community hospital and transferred later to the neurosurgical
      clinic. The data included mechanism of injury and clinical status at admission,
      including the level of consciousness according to the Glasgow Coma Score (GCS)
      before and after resuscitation. After admission, nearly all patients below a
      score of 8 were intubated and treated with controlled ventilation until the
      patient awakened, died, or had remained in a steady state for approximately 3
      weeks. Assessment of the final outcome was made according to the Glasgow Outcome
      Scale (GOS) both at discharge and again after the patient's status was
      stabilized. The results show a stable yearly outcome during the 21 years of
      recording but a significantly improved good recovery and mortality rate when
      compared with our previous results. Outcome was significantly correlated to age
      and type and severity of lesion, as judged by the postresuscitation GCS. The
      outcome of the 1264 most severely injured, comatose patients (GCS < 9) shows a
      good recovery rate of 55%, a severely disabled rate of 14%, a vegetative rate of
      7%, and a mortality rate of 24%. We attribute these results, which compare
      favorably with others, to prompt airway control and controlled ventilation in
      unconscious patients.

PMID- 8563444
TI  - Brain tumors do not affect thiopental dosing requirements.
AB  - We used the biphasic electroencephalographic (EEG) response to increasing
      concentrations of thiopental to measure regional brain responses to thiopental.
      Eight patients with cortical parietal brain tumors, 3.3 (SD 1.3) cm in diameter,
      and eight control patients with lung cancer and normal brain computed tomography
      scans received thiopental by infusion (50-75 mg/min) until burst suppression (50%
      isoelectric activity) on the EEG occurred. Infusion lasted 10.7 (SD 2.4) min, and
      the average dose of thiopental administered was 810 (SD 170) mg [11.2 (SD 1.9)
      mg/kg]. During infusion the EEG was continuously recorded from the F3, F4, P3,
      and P4 electrodes. On-line power spectral analysis was performed, and data were
      saved for later analysis. Four EEG parameters [log beta (15-30 Hz) power, percent
      beta power, spectral edge 95% and spectral edge 70%] were plotted against
      calculated brain concentration of thiopental [using an assumed plasma-effect site
      rate constant (ke0) of 0.58] for each individual. Three points were measured on
      each curve (50% upslope, peak, and zero intercept) to quantitate the EEG
      response. Statistical comparisons were performed between the following sets of
      data: EEG response at electrode closest to brain tumor versus electrode farthest
      from tumor (in the same patient); and electrodes closest to brain tumors
      (parietal P3 and P4) versus same electrode pair in control patients (patients
      with thoracic tumors) using analysis. No differences were found in any
      comparison. Thus, the presence of a brain tumor does not affect the response of
      the brain in this region to thiopental as measured using EEG.

PMID- 8563445
TI  - Effect of plasma anticonvulsant level on pipecuronium-induced neuromuscular
      blockade: preliminary results.
AB  - Patients receiving anticonvulsants are resistant to nondepolarizing muscle
      relaxants (NDMR). This study examines the effect of plasma anticonvulsant levels
      on pipecuronium-induced neuromuscular blockade. Twenty adult patients scheduled
      for neurosurgery were assigned to one of two groups. Group 0 (G0) consisted of 10
      patients not on anticonvulsant therapy; group 1 (G1) included 10 patients treated
      either with phenytoin or carbamazepine. G1 patients were further divided into G1u
      (n = 4) and G1w (n = 6) subgroups, according to the plasma anticonvulsant level
      measured the day before surgery--under (G1u) or within (G1w) the therapeutic
      range. Neuromuscular transmission was monitored with a Biometer International A/S
      Accelograph. Anesthesia was induced and maintained using propofol and sufentanil.
      After calibration of the accelograph, a bolus of pipecuronium 0.08 mg/kg was
      given IV. The time from pipecuronium injection to the peak reduction of T1 was
      taken as the onset time. The time in min from pipecuronium injection to recovery
      of T1% (first accelograph response/baseline response) x 100 and TR% (fourth
      accelograph response/first accelograph response) x 100 were recorded at 25, 50,
      and 75% of baseline. The recovery index (RI) was taken as the time from 25 to 75%
      of baseline. The recovery index (RI) was taken as the time from 25 to 75%
      recovery of the baseline response. The onset time was not different in G0 (203 +/
      60.4 s), G1 (230.5 +/- 79.3 s), and G1u (181.8 +/- 60.4 s) but prolonged in G1w
      (279.2 +/- 67.7 s).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8563446
TI  - Propylene glycol toxicity caused by prolonged infusion of etomidate.
AB  - We describe a case of propylene glycol toxicity due to intravenous administration
      of etomidate for cerebral protection. A continuous etomidate infusion was
      titrated to burst suppression of the electroencephalogram during surgical
      resection of a large intracranial arteriovenous malformation. The etomidate
      formulation used (Amidate, Abbot) contains etomidate 2 mg/ml in a 35% propylene
      glycol vehicle. A total of 5 g/kg of the solvent was given during 12 h. Adverse
      effects of propylene glycol were observed including hyperosmolality with an
      increased osmolal gap, hemolysis, hemoglobinuria, and metabolic acidosis.
      Normalization of these metabolic and ionic alterations occurred after 12 h of
      discontinuation of the infusion. The potential toxicity of the solvent should be
      considered during long-term administration of etomidate.

PMID- 8563447
TI  - In vitro cerebral vasoactive effects of MK-801.
AB  - MK-801, although more consistently neuroprotective in focal ischemia, has had
      more variable success in the management of global ischemia. This difference could
      be due to a vasoactive effect that would improve blood flow in focal ischemia but
      would not be operative in global ischemia. Therefore, a possible direct
      cerebrovascular effect of MK-801 was investigated in vitro in basilar arteries
      from 13 dogs and 16 guinea pigs. Two rings were obtained from each animal; in one
      the endothelium was removed and in the other the endothelium was maintained
      intact. Each ring was suspended in an organ bath and isometric tension was
      recorded. After half-maximal contractions with either KCl or 5-hydroxytryptamine,
      a dose of MK-801 or the same volume of saline was added to the bath. MK-801
      concentrations between 0.1 and 1.0 microM had no effect on both canine and guinea
      pig basilar arteries with or without endothelium whereas concentrations 10-160
      microM further contracted the arteries in an endothelium dependent fashion, with
      the exception of the KCl precontracted endothelium intact canine artery. Higher
      concentrations of MK-801 tended to dilate the arteries and the dilation was
      endothelium independent. Thus, MK-801 has dose-dependent cerebral vascular
      effects and our results may explain some of the conflicting results of MK-801 on
      CBF.

PMID- 8563448
TI  - Attenuation of midazolam-induced EEG activation in rats by both flumazenil and
      hyperbaric oxygen.
AB  - Sedative doses of benzodiazepines, i.e., midazolam, can cause
      electroencephalography (EEG) activation, which is reversed by the benzodiazepine
      antagonist flumazenil. Hyperbaric oxygen (HBO) can cause acute cerebral toxicity
      with sensory and motor abnormalities, including seizures. Benzodiazepines are
      also administered for anxiolysis, sedation, and seizure prophylaxis to patients
      receiving HBO treatments. Because of possible interactions on monitored
      neuroelectric activity, we decided to evaluate the effects of midazolam on the
      EEG and cortical somatosensory evoked potentials (CEPs) in rats exposed to HBO,
      as well as to compare this to the effects of flumazenil. Thirty-six Sprague
      Dawley rats were studied. Analog 2-channel and computerized EEG analysis
      (compressed spectral array with spectral edge, power spectrum, and power bands)
      and CEPs were monitored. Studies were divided into two phases. In phase 1, after
      baseline recordings, 16 rats were randomly assigned to receive midazolam, 0.1
      mg.kg-1 intravenously, then compression to 1,824 mm Hg of O2 (n = 8), or 1,824 mm
      Hg of O2 followed by the midazolam (n = 8). In phase 2, after baseline
      recordings, rats were randomly assigned to four (n = 5) groups: midazolam, 0.1
      mg.kg-1 intravenously, then compression to 1,824 mm Hg of O2; midazolam, then
      flumazenil, 0.05 mg.kg-1 intravenously; compression, then midazolam; or
      flumazenil, then midazolam. Recordings of EEG and CEPs were compared by analysis
      of variance and the Student's t test. In phase 1, midazolam first showed EEG
      activation in six (75%) rats, which was reversed by HBO. The HBO first activated
      the EEG in two rats (25%); midazolam then given had no effect. The CEPs were not
      altered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8563449
TI  - Comparison of extracellular dopamine concentration in awake unstressed and
      postsurgical nitrous oxide sedated rats.
AB  - Nitrous oxide (N2O), 70%, in O2 is often used as a control condition after
      surgical preparation in rodents undergoing neuroscience investigations. Concern
      has been expressed that this constitutes a stressful condition. Microdialysis was
      used in 15 rats to assess extracellular striatal dopamine concentrations during
      overnight soundproof isolation and on the following day after vascular
      cannulation and halothane excretion under N2O sedation with concomitant
      neuromuscular blockade. The overnight dialysate dopamine concentration was 22.8
      +/- 8.7 pg/40 microliters. Thirty minutes after stopping halothane, the dialysate
      concentration was 362.6 +/- 91.6 pg/40 microliters during postsurgical N2O
      sedation. These data indicate that (a) compared to an unstressed baseline,
      significant brain dopamine effects occur with N2O sedation after surgery with
      halothane N2O anesthesia, and (b) baseline conditions can have a major effect on
      microdialysis data expressed as percentage of baseline.

PMID- 8563450
TI  - Neuromonitoring during hypothermic cardiopulmonary bypass.
AB  - To reduce the incidence of neurological and neuropsychological dysfunction
      following hypothermic cardiopulmonary bypass (CPB), central nervous system (CNS)
      monitoring before, during, and after CPB seems to be necessary. Compared to the
      total scope of hemodynamic monitoring CNS monitoring, however, is mostly
      investigational and infrequently used in clinical routine, and the impact on
      postoperative outcome is still being discussed. An optimal CNS monitoring would
      have to include continuous objective measurement of brain function, perfusion,
      and metabolism with regard to patients' disease and would also have to be adapted
      to the technique applied and the period of CPB. Over the past few years a number
      of monitoring devices (computer-processed electroencephalogram, jugular bulb
      saturation, Doppler flow measurement, near infrared spectroscopy) have been
      evaluated. Each of them has a specific diagnostic power so that a combination of
      only two or more devices will meet the criteria for effective brain monitoring.
      In addition, the impact on outcome and the applicability and cost-effectiveness
      of these tools will have to be investigated in the future.

PMID- 8563451
TI  - Hippocratic medicine and Aristotelian science in the Daemonum investigatio
      peripatetica of Andrea Cesalpino.

PMID- 8563452
TI  - Making it in a man's world: the late-nineteenth-century surgical career of Mary
      Amanda Dixon Jones.

PMID- 8563453
TI  - Linking midwives and abortion in the Progressive Era.

PMID- 8563454
TI  - Discipline, obedience, and female support groups: Mona Wilson at the Johns
      Hopkins Hospital School of Nursing, 1915-1918.

PMID- 8563455
TI  - The autonomic nervous system and the regulation of arterial tone in migraine.
AB  - Abnormal regulation of the large cranial arteries seems to play a significant
      role in the mechanisms of migraine pain. Thus, vasodilatation of extra- and
      intracranial conductance arteries has been described both during spontaneous
      migraine attacks and during experimentally provoked vascular headaches. The
      regulation of the diameter of these arteries is complex and involves autonomic,
      trigeminovascular, endothelial and humoral mechanisms. Studies concerned with the
      function of the autonomic nervous system in migraine suggest that a mild
      parasympathetic dysfunction may be present. Cerebral arteries in migraineurs are
      hypersensitive to nitric oxide, which may induce migraine attacks. As the enzyme
      responsible for nitric oxide synthesis is present in parasympathetic nerve
      endings around cerebral arteries, this supports a role for the parasympathetic
      nervous system in migraine. In addition, vasoactive transmitters released from
      perivascular trigeminal nerve endings may be implicated. Several of these aspects
      are closely linked to the presumed mechanisms of action of modern migraine
      therapeutics.

PMID- 8563456
TI  - Neurally mediated syncope and serotonin reuptake inhibitors.
AB  - Serotonin (5-hydroxytryptamine or 5HT) is a neurotransmitter which appears to
      play a prominent role in central regulation of heart rate and blood pressure.
      Recent evidence suggests that the activation of cerebral serotonin receptors
      results in a depressor effect principally through sympatho-inhibition. Several
      common clinical disorders resulting in hypotension leading to syncope are
      neurally mediated syncope, carotid sinus hypersensitivity and orthostatic
      hypotension, each of which may involve a serotonergic component. This brief
      review provides a summary of serotonergic blood pressure regulation, as well as
      the initial experience with the clinical effects of the serotonin reuptake
      inhibitors in the therapy of the aforementioned disorders.

PMID- 8563457
TI  - Observations on midodrine in a case of vasodepressor neurogenic syncope.
AB  - A 43-year-old man presented with recurrent syncope and dizziness after he had a
      dual chamber pacemaker fitted for presumed sino-atrial disease. Head-up tilt
      produced vasodepressor neurocardiogenic syncope, despite appropriate heart rate
      support during pacing, and reproduced symptoms. Symptoms were not improved by
      disopyramide. A double-blind cross-over trial of midodrine, an alpha-receptor
      agonist, was effective in reducing symptoms: it abolished syncope and reduced
      frequency and severity of dizziness, coupled with improved haemodynamic responses
      to head-up tilt.

PMID- 8563458
TI  - The relationship between heart rate variability and measures of body habitus.
AB  - There is a well-recognized relationship between autonomic nervous system function
      and body habitus although few studies have addressed the role of the
      parasympathetic nervous system. A decrease in parasympathetic nervous-system
      mediated heart rate variability in obesity may in part explain the mortality and
      morbidity that are associated with the obese state. We used multiple linear
      regression techniques to explore the relationship between measures of heart rate
      variability and anthropometric indices in 597 male participants in the Normative
      Aging Study. After adjustment for age and log10 heart rate, weight and body mass
      index were significant predictors of both the expiratory to inspiratory ratio
      (E/I ratio) and the difference between maximum and minimum heart rate (HRMax
      Min). The abdomen-to-hip ratio and percentage body fat were not significant
      predictors of measures of heart rate variability. A one standard deviation change
      in the anthropometric index (weight, body mass index) resulted in a decrease in
      the E/I ratio of 0.010-0.014 and a decrease in the HRMax-Min of 0.486-0.715
      beats/min. A change in the anthropometric index across the distribution (5-95
      percentile) resulted in a decrease in the E/I ratio of 0.032-0.037 and a decrease
      in the HRMax-Min of 1.56-2.39 beats/min. These results indicate that heart rate
      variability and overall body size are correlated. This association could in part
      explain the mortality and morbidity that is associated with the obese state.

PMID- 8563459
TI  - Autonomic dysreflexia in tetraplegic patients: evidence for alpha-adrenoceptor
      hyper-responsiveness.
AB  - A controlled study of acute pharmacological intervention was designed to
      determine whether decreased sympathetic nerve activity in tetraplegic patients
      results in increased responsiveness of alpha-adrenoceptors which might contribute
      to vascular hyperreactivity and the clinical scenario of autonomic dysreflexia.
      The study took place in a university teaching hospital and included six male
      tetraplegic patients and six age-matched normal male controls. All tetraplegics
      were 5 months or longer post-traumatic spinal cord injury and all had experienced
      symptoms of autonomic dysreflexia on at least one occasion. The dorsal foot vein
      diameter was recorded with a tonometer during local infusions of noradrenaline
      0.125-256 ng/min given through a short intravenous needle. In tetraplegic
      patients, there was a significant shift to the left of the dose-response curve
      indicating increased venous responsiveness to noradrenaline. The concentration of
      noradrenaline required to cause a 50% reduction of the resting vein diameter was
      decreased in tetraplegics (1.6 ng/min, geometric mean) compared to normal
      controls (10.9 ng/min, p < 0.02). alpha-Adrenoceptor responsiveness in dorsal
      foot veins is increased in patients with tetraplegia. Hypersensitivity of
      vascular alpha-adrenoceptors may contribute to autonomic dysreflexia in patients
      with high spinal cord injury.

PMID- 8563460
TI  - Interrelationships among measures of autonomic activity and cardiovascular risk
      factors during orthostasis and the oral glucose tolerance test.
AB  - Overstimulation of sympathetic nervous system activity is related to
      atherosclerotic cardiovascular disease risk, but the role of parasympathetic
      activity in this association is not clear. This study evaluated sympathetic and
      parasympathetic function by spectral analysis of heart rate variability and
      plasma levels of norepinephrine (NE) epinephrine (EPI), dihydroxyphenylglycol
      (DHPG), dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC). It
      also examined the interrelationships among these parameters and established
      atherosclerotic cardiovascular disease risk factors in 53 men (mean age 59.5
      years). During supine rest, low-frequency power correlated positively with high
      frequency power (r = 0.58, p < 0.001), plasma NE correlated with plasma DHPG (r =
      0.41, p < 0.001) and plasma DOPA with DOPAC (r = 0.47, p < 0.001) but neither low
      nor high-frequency power was correlated with plasma levels of any catechol.
      Among risk factors, plasma NE correlated with fasting insulin and mean arterial
      blood pressure, and urine NE correlated with body mass index. Both low- and high
      frequency power correlated positively with insulin levels. Orthostasis decreased
      high-frequency power and increased low-frequency power and plasma NE levels.
      During the oral glucose tolerance test, both high- and low-frequency power
      increased, plasma NE levels were unchanged, and plasma EPI levels decreased [88.5
      +/- 18 (SEM) versus 52.5 +/- 12 pM, p = 0.001]. The results suggest that
      orthostasis decreases and the oral glucose tolerance test increases
      parasympathetic outflows, whereas both stimuli increase sympathetic outflows.
      Among all atherosclerotic cardiovascular disease risk factors, hyperinsulinaemia
      showed the strongest association with autonomic nervous system activity,
      especially parasympathetic activity. Estimates of sympathetic responses obtained
      from power spectral analysis of heart rate variability agree poorly with those
      from plasma levels of catechols, possibly because of a parasympathetic
      contribution to low-frequency power and independence of sympathoneural outflows
      to the arm and heart.

PMID- 8563461
TI  - Insulin resistance and autonomic function in traumatic lower limb amputees.
AB  - This study examined plasma insulin response to oral glucose load and autonomic
      nervous system activity in male lower limb amputees (n = 52) aged 50-65 years,
      compared to matched controls (n = 53). The groups had similar body mass index,
      blood pressure and plasma lipid levels. The amputees had higher mean fasting
      plasma insulin levels (18.4 +/- 9.7 (SD) versus 13.7 +/- 5.1 mU/l, p = 0.005) and
      during an oral glucose tolerance test (OGTT) (1 h levels 88.1 +/- 45.3 versus
      62.1 +/- 42.7, p = 0.016) with similar plasma glucose levels, indicating insulin
      resistance. At baseline with the subjects supine, there were no group differences
      in low- or high-frequency power of heart rate variability or in plasma levels of
      norepinephrine (NE) or epinephrine (EPI). In response to orthostasis, the groups
      had similarly increased plasma NE levels. During the OGTT, amputees had
      significantly larger increments in low-frequency power than did controls (2.2 +/-
      1.3 versus 1.6 +/- 0.9 (beats/min)2 respectively, p < 0.01) and plasma NE levels
      increased significantly in amputees (1595 +/- 849 versus 1941 +/- 986 pM, p =
      0.0008) but not in controls. At 1 h after glucose administration, plasma EPI
      levels were decreased significantly from baseline in both groups; at both 1 and 2
      h after glucose administration, plasma EPI levels were higher in the amputees
      than controls. Amputees appear to have a combination of enhanced sympathoneural
      responsiveness and attenuated suppression of adrenomedullary secretion during
      glucose challenge. As catecholamines antagonize insulin effects, one possible
      explanation for insulin resistance in amputees is hyperglycaemia-induced
      sympathoneural activation and a failure of hyperglycaemia to decrease
      adrenomedullary secretion.

PMID- 8563462
TI  - Effect of neurovestibular stimulation on autonomic regulation.
AB  - Conditions associated with nausea and vomiting, such as motion sickness or side
      effects of medications, are commonly associated with a clinical picture
      consistent with parasympathetic activation and sympathetic withdrawal. It can be
      postulated, therefore, that vestibular stimulation contributes to sympathetic
      withdrawal. To test this hypothesis five normal volunteers, 24-33 years old, were
      studied during caloric vestibular stimulation while monitoring muscle sympathetic
      nerve activity directly through a needle electrode placed in a peroneal nerve.
      The ear was irrigated with water at a flow rate of 450 ml/min and 37 degrees C.
      The water temperature was sequentially lowered by 7 degree C intervals until
      intolerable side effects developed or a temperature of 16 degrees C was reached.
      Nystagmus was induced in all subjects, but heart rate, blood pressure, muscle
      sympathetic nerve activity and plasma norepinephrine levels did not change
      significantly during or after caloric stimulation, even when the subjects felt
      dizzy and nauseated. No evidence of sympathetic withdrawal was observed in any
      subject either by muscle sympathetic nerve activity or plasma norepinephrine
      measurements. In conclusion, we have found that selective vestibular stimulation
      is not accompanied by significant changes in the sympathetic nervous system
      function. In particular, no sympathetic withdrawal was observed. It could be
      argued that lack of sympathetic stimulation is an inadequate response to the
      symptoms associated with caloric stimulation.

PMID- 8563463
TI  - Artefacts in standard and time-dependent spectral analysis of arterial blood
      pressure signals obtained by Finapres: importance and correction.
AB  - The non-invasive Finapres (finger arterial pressure) device is widely used for
      the measurement of arterial blood pressure (BP) in BP variability studies, in
      particular in experimental studies. In our work, we have noticed that the
      calibration pauses of the Finapres, occurring approximately every 80 heart beats,
      introduce artefacts in standard and time-dependent spectral analysis of the
      arterial BP signal. This report describes these artefacts and indicates their
      dependence on the heart rate (HR) of the subject. In standard spectral analysis,
      they appear principally for low HR subjects, whereas in time-dependent spectral
      analysis, they distort the time-dependent spectrum both for low and high HR
      subjects. A possible correction procedure is presented which eliminates these
      pauses, causing minimal distortion from the original arterial BP time series.
      This correction keeps the total time-duration of the corrected signal equal to
      that of the original signal, thus allowing reliable spectral analysis of arterial
      BP fluctuations to be performed.

PMID- 8563464
TI  - Calibration of ring-current effects in proteins and nucleic acids.
AB  - Density functional chemical shielding calculations are reported for methane
      molecules placed in a variety of positions near aromatic rings of the type found
      in proteins and nucleic acids. The results are compared to empirical formulas
      that relate these intermolecular shielding effects to magnetic anisotropy ('ring
      current') effects and to electrostatic polarization of the C-H bonds. Good
      agreement is found between the empirical formulas and the quantum chemistry
      results, allowing a reassessment of the ring-current intensity factors for
      aromatic amino acids and nucleic acid bases. Electrostatic interactions
      contribute significantly to the computed chemical shift dispersion. Prospects for
      using this information in the analysis of chemical shifts in proteins and nucleic
      acids are discussed.

PMID- 8563465
TI  - Internal mobility of cyclic RGD hexapeptides studied by 13C NMR relaxation and
      the model-free approach.
AB  - The internal mobility of three isomeric cyclic RGD hexapeptides designed to
      contain two beta-turns in defined positions, cyclo(Arg-Gly-Asp-Gly-D-Pro-Pro)
      (I), cyclo(Arg-Gly-Asp-D-Pro-Gly-Pro) (II) and cyclo(Arg-Gly-Asp-D-Pro-Pro-Gly)
      (III), have been studied by 13C NMR longitudinal and transverse relaxation
      experiments and measurements of steady-state heteronuclear (1H)-13C NOE
      enhancement with 13C at natural abundance. The data were interpreted according to
      the model-free formalism of Lipari and Szabo, which is usually applied to data
      from macromolecules or larger sized peptides with overall rotational correlation
      times exceeding 1 ns, to yield information about internal motions on the 10-100
      ps time scale. The applicability of the model-free analysis with acceptable
      uncertainties to these small peptides, with overall rotational correlation times
      slightly below 0.3 ns, was demonstrated for this specific instance. Chemical
      exchange contributions to T2 from slower motions were also identified in the
      process. According to the order parameters obtained for its backbone alpha-carbon
      atoms, II has the most rigid backbone conformation on the 10-100 ps time scale,
      and I the most flexible. This result coincides with the results of earlier NMR
      constrained conformational searches, which indicated greatest uncertainty in the
      structure of I and least in II.

PMID- 8563466
TI  - Assignment and modeling of the Rev Response Element RNA bound to a Rev peptide
      using 13C-heteronuclear NMR.
AB  - The Rev Response Element (RRE) RNA-Rev protein interaction is important for
      regulation of gene expression in the human immunodeficiency virus. A model system
      for this interaction, which includes stem IIB of the RRE RNA and an arginine-rich
      peptide from the RNA-binding domain of Rev, was studied using multidimensional
      heteronuclear NMR. Assignment of the RNA when bound to the peptide was obtained
      from NMR experiments utilizing uniformly and specifically 13C-labeled RNA.
      Isotopic filtering experiments on the specifically labeled RNA enable unambiguous
      assignment of unusual nonsequential NOE patterns present in the internal loop of
      the RRE. A three-dimensional model of the RNA in the complex was obtained using
      restrained molecular dynamics calculations. The internal loop contains two purine
      purine base pairs, which are stacked to form one continuous helix flanked by two
      A-form regions. The formation of a G-G base pair in the internal loop requires an
      unusual structure of the phosphate backbone. This structural feature is
      consistent with mutational data as being important for the binding of Rev to the
      RRE. The G-G base pair may play an important role in opening the normally narrow
      major groove of A-form RNA to permit binding of the Rev basic domain.

PMID- 8563467
TI  - Interproton distance bounds from 2D NOE intensities: effect of experimental noise
      and peak integration errors.
AB  - The effect of experimental and integration errors on the calculation of
      interproton distances from NOE intensities is examined. It is shown that NOE
      intensity errors can have a large impact on the distances determined. When
      multiple spin ('spin diffusion') effects are significant, the calculated
      distances are often underestimated, even when using a complete relaxation matrix
      analysis. In this case, the bias of distances to smaller values is due to the
      random errors in the NOE intensities. We show here that accurate upper and lower
      bounds of the distances can be obtained if the intensity errors are properly
      accounted for in the complete relaxation matrix calculations, specifically the
      MARDIGRAS algorithm. The basic MARDIGRAS algorithm has been previously described
      [Borgias, B.A. and James, T.L. (1990) J. Magn. Reson., 87, 475-487]. It has been
      shown to provide reasonably good interproton distance bounds, but experimental
      errors can compromise the quality of the resulting restraints, especially for
      weak cross peaks. In a new approach introduced here, termed RANDMARDI (random
      error MARDIGRAS), errors due to random noise and integration errors are mimicked
      by the addition of random numbers from within a specified range to each input
      intensity. Interproton distances are then calculated for the modified intensity
      set using MARDIGRAS. The distribution of distances that define the upper and
      lower distance bounds is obtained by using N randomly modified intensity sets.
      RANDMARDI has been used in the solution structure determination of the
      interstrand cross-link (XL) formed between 4'-hydroxymethyl-4,5',8
      trimethylpsoralen (HMT) and the DNA oligomer d(5'-GCGTACGC-3')2 [Spielmann, H.P.
      et al. (1995) Biochemistry, 34, 12937-12953]. RANDMARDI generates accurate
      distances bounds from the experimental NOESY cross-peak intensities for the fixed
      (known) interproton distances in XL. This provides an independent internal check
      for the ability of RANDMARDI to accurately fit the experimental data. The XL
      structure determined using RANDMARDI-generated restraints is in good agreement
      with other biophysical data that indicate that there is no bend introduced into
      the DNA by the cross-link. In contrast, isolated spin-pair approximation
      calculations give distance restraints that, when applied in a restrained
      molecular dynamics protocol, produce a bent structure.

PMID- 8563468
TI  - Conformation of the circular dumbbell d<pCGC-TT-GCG-TT>: structure determination
      and molecular dynamics.
AB  - The circular DNA decamer 5'-d<pCGC-TT-GCG-TT>-3' was studied in solution by means
      of NMR spectroscopy and molecular dynamics in H2O. At a temperature of 269 K, a
      50/50 mixture of two dumbbell structures (denoted L2L2 and L2L4) is present. The
      L2L2 form contains three Watson-Crick C-G base pairs and two two-residue loops is
      opposite parts of the molecule. On raising the temperature from 269 K to 314 K,
      the L2L4 conformer becomes increasingly dominant (95% at 314 K). This conformer
      has a partially disrupted G(anti)-C(syn) closing base pair in the 5'-GTTC-3' loop
      with only one remaining (solvent-accessible) hydrogen bond between NH alpha of
      the cytosine dC(1) and O6 of the guanine dG(8). The opposite 5'-CTTG-3' loop
      remains stable. The two conformers occur in slow equilibrium (rate constant 2-20
      s-1). Structure determination of the L2L2 and L2L4 forms was performed with the
      aid of a full relaxation matrix approach (IRMA) in combination with restrained
      MD. Torsional information was obtained from coupling constants. Coupling constant
      analysis (3JHH, 3JHP, 3JCP) gave detailed information about the local geometry
      around backbone torsion angles beta, gamma, delta, and epsilon, revealing a
      relatively high flexibility of the 5'-GTTC-3' loop. The values of the coupling
      constants are virtually temperature-independent. 'Weakly constrained' molecular
      dynamics in solvent was used to sample the conformational space of the dumbbell.
      The relaxation matrices from the MD simulation were averaged over <r-3> to
      predict dynamic NOE volumes. In order to account for the 1:1 conformational
      mixture of L2L2 and L2L4 present at 271 K, we also included S2 factors and <r-6>
      averaging of the <r-3>-averaged relaxation matrices. On matrix averaging, the
      agreement of NOE volumes with experiment improved significantly for protons
      located in the thermodynamically less stable 5'-GTTC-3' loop. The difference in
      stability of the 5'-CTTG-3' and 5'-GTTC-3' loops is mainly caused by differences
      in the number of potential hydrogen bonds in the minor groove and differences in
      stacking overlap of the base pairs closing the minihairpin loops. The syn
      conformation for dC(1), favored at high temperature, is stabilized by solvation
      in the major groove. However, the conformational properties of the dC(1) base, as
      deduced from R-factor analysis and MD simulations, include a large flexibility
      about torsion angle chi.

PMID- 8563469
TI  - Triple resonance HNCCCH experiments for correlating exchangeable and
      nonexchangeable cytidine and uridine base protons in RNA.
AB  - A set of triple resonance experiments is presented, providing through-bond H2N/HN
      to H6 connectivities in uridines and cytidines in 13C-/15N-labeled RNAs. These
      connectivities provide an important link between the sequential assignment
      pathways for the exchangeable and nonexchangeable proton resonances in nucleic
      acids. Both 2D and pseudo-3D HNCCCH experiments were applied to a 30-nucleotide
      lead-dependent ribozyme, known as the leadzyme. The HN to H6 connectivities for
      three uridines in the leadzyme were identified from one 2D H(NCCC)H experiment,
      and the H2N to H6 connectivities were identified for seven of the eight cytidines
      from the combination of a 2D H(NCCC)H and a pseudo-3D H(NCC)CH experiment.

PMID- 8563470
TI  - Dominant negative and DNA-binding properties of mutant thyroid hormone receptors
      that are defective in homodimerization but not heterodimerization.
AB  - Thyroid hormone receptors (TRs) bind to thyroid hormone response elements (TREs)
      as monomers, homodimers, and heterodimers. Mutations that cause resistance to
      thyroid hormone (RTH) have proven useful for identifying important functional
      domains in the receptor. Previous studies have shown that RTH mutants must retain
      the ability to form heterodimers with RXR to exert dominant negative inhibition
      of wild-type receptor function. In this report, we examined in detail the
      dimerization properties, function, and dominant negative activity of RTH
      mutations at R316H and R338W--two mutations that have a propensity to cause the
      pituitary form of RTH. These mutants show selective loss of homodimerization,
      with preservation of heterodimerization with RXR alpha. The selective loss of
      homodimerization was independent of the orientation of the half sites in the TRE.
      The R316H mutant was transcriptionally inactive in transient expression assays,
      consistent with its markedly reduced T3 binding. In contrast, R338W was activated
      at nanomolar concentrations of T3, precluding quantitative analyses of its
      dominant negative properties. In cotransfection assays with wild-type TR beta,
      the R316H mutant functioned in a dominant negative manner to block positively
      (TRE-pal; DR4) and negatively (TSH alpha) regulated reporter genes, although its
      inhibitory potential was reduced compared with other RTH mutants. Introduction of
      the R316H mutation into a receptor containing a potent RTH mutant (G345R) reduced
      its dominant negative activity to the level of the R316H mutant alone. These
      results suggest that mutations that alter homodimerization have reduced dominant
      negative activity for some target genes, a feature that may account, in part, for
      phenotypic variability in RTH.

PMID- 8563471
TI  - A novel point mutation (R243Q) in exon 7 of the c-erbA beta thyroid hormone
      receptor gene in a family with resistance to thyroid hormone.
AB  - Resistance to thyroid hormone (RTH) is characterized by variable tissue
      hyporesponsiveness to thyroid hormones. Recently, a large number of different
      point mutations have been identified in the c-erbA beta thyroid hormone receptor
      (TR beta) in subjects with RTH. We describe a Japanese family with RTH with a
      novel point mutation in exon 7 of the TR beta gene. A single nucleotide
      substitution, guanine for adenine, was identified at the second position of codon
      243 located in the hinge domain between the ligand binding and DNA binding
      domains in one of the two alleles of the proband and his mother, resulting in the
      substitution of the normal arginine (CGG) with a glutamine (CAG). Except for one
      family, point mutations so far described in RTH are clustered at exons 8-10 of
      the TR beta gene. This report presents a novel mutation in the characteristic
      portion in exon 7 of the TR beta.

PMID- 8563472
TI  - Effect of estrogen replacement therapy upon bone mineral density in thyroxine
      treated postmenopausal women with a past history of thyrotoxicosis.
AB  - We have shown that previous thyrotoxicosis and subsequent levothyroxine (L-T4)
      therapy are together associated with reduction in femoral and lumbar vertebral
      bone mineral density (BMD) in postmenopausal women. To determine whether estrogen
      replacement therapy exerts a beneficial effect upon bone loss in this situation,
      we performed a cross-sectional study comparing BMD measurements of the femur and
      lumbar spine in four groups of women (n = 15 in each group) matched for age and
      duration of menopause: (i) those with a previous history of thyrotoxicosis who
      were subsequently receiving both L-T4 and estrogen replacement therapy for at
      least 3 years (L-T4 + HRT group), (ii) previously thyrotoxic women matched to
      group (i) for L- dose and duration who had never used estrogen replacement (L-T4
      alone group), (iii) those with no history of thyroid disease who had received
      estrogen replacement therapy for at least 3 years (HRT alone group), and (iv)
      those with no history of thyroid disease who had never received estrogen
      replacement therapy (control group). BMD measurements were higher at each site in
      the HRT alone group than in controls (6.0-13.6% increases in BMD, p < 0.05 for
      measurements at femoral neck, Ward's triangle, and trochanter) while measurements
      of BMD were lower at each site in the L-T4 alone group than in controls (3.3-6.1%
      reductions in BMD), although values did not reach statistical significance.
      Measurements at each site in the L-T4 + HRT group were higher than those from the
      L-T4 alone group (2.2-16.1% increases in BMD, p < 0.05 for measurements at lumbar
      spine), although lower than in the group receiving HRT alone (p < 0.05 for
      femoral neck and Ward's triangle) and similar to those in untreated controls. Our
      results indicate that estrogen replacement therapy abolishes reduction in femoral
      and vertebral BMD in postmenopausal women with previous thyrotoxicosis and
      subsequent L-T4 therapy. This potentially beneficial influence of estrogen
      replacement upon both BMD and fracture risk in postmenopausal women with a
      history of thyroid disease suggests that estrogen administration should be
      encouraged in this group.

PMID- 8563473
TI  - Childhood thyroid diseases around Chernobyl evaluated by ultrasound examination
      and fine needle aspiration cytology.
AB  - Screening by ultrasound examination and fine-needle aspiration cytological biopsy
      (FNA) was conducted in five regions in Belarus, Ukraine, and Russia to
      investigate the prevalence of childhood thyroid diseases around Chernobyl. Gomel,
      Zhitomir, Kiev, and the western area of Bryansk are the administrative regions
      where severe radioactive contamination occurred. The subjects from Mogilev, where
      contamination was relatively low, served as controls. Among 55,054 subjects
      (26,406 boys and 28,648 girls), the prevalence of ultrasonographic thyroid
      abnormalities such as nodule, cyst, and abnormal echogenity was significantly
      higher in the regions with severe contamination than in Mogilev. Of the 1,396
      children showing echographic thyroid abnormalities 197 were selected for FNA, and
      a sample was successfully obtained for diagnosis from 171 (51 boys and 120 girls)
      of the 197 subjects. The aspirate was insufficient for diagnosis in the remaining
      26 subjects. Thyroid cancer was encountered in four children (2.3%) from the
      contaminated regions, two children being from Gomel. The other thyroid diseases
      were follicular neoplasm, 6.4%; adenomatous goiter, 18.7%; chronic thyroiditis,
      31.0%; and cyst, 24.0%, suggesting that a major cause of thyroid nodularity is
      nonneoplastic changes, mainly chronic thyroiditis and cysts. These results will
      serve as an important data base for further analyses and suggest that childhood
      thyroid diseases, including both neoplasms and immunological disorders, are
      consequences of radioactive fallout.

PMID- 8563474
TI  - Copulsatile release of thyrotropin and prolactin in normal and hypothyroid
      subjects.
AB  - In healthy subjects, thyroid-stimulating hormone (TSH) and prolactin (PRL) are
      secreted in a pulsatile fashion. However, the factors that control the generation
      of these pulses are unknown. Since thyrotropin-releasing hormone (TRH) and
      dopamine (DA) affect levels of both hormones, pulsatile TRH or DA input to the
      pituitary gland may lead to pulsatile secretion of both TSH and PRL. In this
      case, TSH and PRL should exhibit significant nonrandom pulse concordance rates.
      To test this hypothesis, we studied 11 healthy subjects (5 women in the early
      follicular phase and 6 men) and 11 subjects with primary hypothyroidism (5
      untreated and 6 euthyroid on 1-thyroxine therapy). To further test the specific
      hypothesis that pulsatile TRH entrains pulsatile TSH and PRL secretion, we
      restudied the 6 treated hypothyroid subjects on the final day of a 9-day constant
      infusion of TRH. In each study, blood samples were drawn every 15 min for 24 h,
      and TSH and PRL levels were measured by immunoradiometric assays. Hormone pulses
      were located by Cluster analysis. Nonrandom TSH and PRL pulse coincidence rates
      were assessed by a statistically based computer algorithm, which compares
      observed pulse concordance rates to those expected by chance. In the healthy men
      and women and the treated hypothyroid subjects, TSH and PRL were copulsatile in a
      significantly nonrandom fashion. Of TSH pulses 36-45% occurred within 15 min of
      PRL pulses, while 37-67% of PRL pulses occurred within 15 min of TSH pulses.
      Similar pulse concordance rates were seen in treated hypothyroid subjects
      receiving constant TRH infusions. Thus, there appears to be a central factor or
      factors that stimulate the copulsatile release of TSH and PRL. However, TRH does
      not appear to play a role in this phenomenon, and the underlying pulse
      generator(s) for both hormones remains to be elucidated.

PMID- 8563475
TI  - Intercellular adhesion molecule-1 (ICAM-1) in the sera of patients with Graves'
      disease: correlation with disease activity and treatment status.
AB  - Intercellular adhesion molecule (ICAM-1), a ligand for lymphocyte function
      associated antigen-1 (LFA-1), plays an important role in a variety of immune
      mediated mechanisms such as lymphocyte attachment to cultured Graves' thyroid
      cells. We report the detection of a soluble form of the ICAM-1 molecule (sICAM-1)
      in sera from patients with Graves' disease (GD) and other thyroid disorders. The
      mean (+/- SD) sICAM-1 concentration in 28 euthyroid control subjects was 1931 +/-
      681 pmol/L. The mean sICAM-1 concentration in 25 untreated hyperthyroid patients
      with GD was significantly elevated (3065 +/- 890 pmol/L), and decreased
      significantly (2489 +/- 845 pmol/L) after treatment with antithyroid drugs and/or
      131I. Of 14 GD patients who had been in remission following administration of
      antithyroid drugs, 12 had recurrent disease. In 10 of the 12 patients in whom GD
      recurred, the sICAM-1 concentration (3807 +/- 796 pmol/L) increased
      significantly. The mean sICAM-1 concentration in patients with hypothyroidism due
      to chronic thyroiditis (n = 15:2895 +/- 569 pmol/L) was significantly elevated
      over that of control subjects, and not different from untreated hyperthyroid
      patients. The mean sICAM-1 concentration in patients with subacute thyroiditis (n
      = 13: 3036 +/- 441 pmol/L) was significantly elevated, while the mean sICAM-1
      concentration in patients with nodular goiter (n = 10: 2318 +/- 490 pmol/L) was
      within the normal range. These results indicate that mean serum sICAM-1
      concentration was significantly elevated in patients with untreated GD, and it
      decreased after treatment and increased at the time of recurrence. Therefore, the
      elevated serum concentration of sICAM-1 in patient with GD probably reflects
      ongoing immune processes.

PMID- 8563476
TI  - Absence of association between human spumaretrovirus and Graves' disease.
AB  - Graves' disease (GD) is an autoimmune thyroid disease. The etiology of GD is
      still not clear. Both genetic and environmental factors, such as infectious
      agents, are believed to be involved in its pathogenesis. Recent findings suggest
      a role for human spumaretrovirus (HSRV) in the pathogenesis of GD. To test this
      hypothesis, we looked for the HSRV gag region sequence in DNA extracted from the
      peripheral blood leukocytes and thyroid tissue of patients with GD, and controls.
      Genomic DNA was subjected to a highly sensitive nested polymerase chain reaction,
      followed by dot-blot hybridization with an internal probe. HSRV gag region DNA
      fragments were detected in the peripheral blood leukocytes of patients with GD
      and controls to a similar extent; 5.3% (2/38) of Caucasian patients with GD, 4.7%
      (2/43) of Caucasian controls, 4.7% (2/43) of African-American patients with GD,
      and 6.5% of (3/46) African-American controls. Similar values were obtained for
      the samples of thyroid tissues; 5.5% (1/18) of Caucasian patients with GD and
      5.0% (1/20) of controls. The differences in all these comparisons were not
      statistically significant. These results do not support a role for HSRV in the
      pathogenesis of GD.

PMID- 8563477
TI  - Outcome of percutaneous transluminal coronary angioplasty in patients with
      subclinical hypothyroidism.
AB  - To determine the outcomes of percutaneous transluminal angioplasty (PTCA) in
      patients with subclinical hypothyroidism and to compare them with those in
      euthyroid patients, we studied retrospectively 48 hypothyroid (4 overtly and 44
      subclinically hypothyroid) and 122 euthyroid patients who had a PTCA in Boston's
      Beth Israel Hospital between 1984 and 1994. No significant differences were
      detected in bradycardia (relative risk, RR: 0.96), tachyarrhythmia (RR: 0.62),
      heart failure (RR: 2.27), hypotension (RR: 1.95), or bleeding (RR: 2.48) in the
      immediate postprocedure period between euthyroid and subclinically hypothyroid
      patients. There was a trend towards an increased incidence of chest pain (43.2 vs
      27.5%, RR: 1.57, p = 0.084), dissection (50 vs 33%, RR: 1.51, p = 0.06) as an
      immediate, and reocclusion as an early (within 2 weeks) postprocedure
      complication (6.25 vs .9%, RR: 6.81, p = 0.08). However, chest pain accompanied
      by electrocardiographic changes was not significantly different between the two
      groups (20.5 vs 14.7%, RR: 1.4, p = 0.47). There was no difference in the number
      of procedures rated as successful (subclinically hypothyroid vs euthyroid: 90.2
      vs 92.7%). Hospital charges, discharge destination, interval to next admission to
      the hospital, and in-hospital mortality were not different between the two
      groups. Subclinical hypothyroidism does not appear to be a risk factor for
      significant morbidity or increased mortality following PTCA. Prospective long
      term studies with increased statistical power are needed to clarify whether there
      is an association between hypothyroidism and complications (especially chest
      pain, dissection, and/or reocclussion) in the early (2 weeks) and late (6 months)
      post-PTCA period.

PMID- 8563478
TI  - Impaired TSH secretion during sustained hyperglucagonemia in anesthetized dogs.
AB  - We previously demonstrated that hyperglucagonemia may be responsible for thyroid
      hormone alterations noted in some nonthyroidal illnesses. Since TSH secretion is
      also known to be altered in many subjects with several nonthyroidal illnesses, we
      assessed the influence of sustained hyperglucagonemia on TSH secretory pattern in
      5 anesthetized dogs. Serum TSH concentrations were determined after a 16-h fast
      and again at intervals of 15 min during sustained hyperglucagonemia (515-645
      pg/mL) induced by iv bolus administration of glucagon 0.1 mg followed by a
      continuous glucagon infusion 3 ng/kg/min for 3 h. TRH (200 micrograms) was
      administered iv at 60 min to assess the influence of sustained hyperglucagonemia
      on the hypothalamic pituitary thyrotroph axis during the study. A control study
      was also conducted using normal saline instead of glucagon, and both studies were
      performed in a randomized sequence. Basal TSH levels were not significantly
      different during both studies. However, serum TSH declined significantly during
      sustained hyperglucagonemia prior to TRH administration (delta TSH, pre-TRH, 
      0.86 +/- 0.24 vs 0.02 +/- 0.07 ng/mL for normal saline, p < 0.01). Furthermore,
      TSH response to iv TRH administration was significantly blunted during glucagon
      infusion alone as expressed by both the absolute rise (delta TSH, post-TRH, 1.1
      +/- 0.5 vs 5.9 +/- 1.7 ng/ml for normal saline, p < 0.01) as well as an
      integrated response over a 2-h period (sigma TSH, post-TRH, 4.0 +/- 1.1 vs 11.7
      +/- 3.5 ng/min/mL, p < 0.001). Therefore, this study demonstrates that sustained
      hyperglucagonemia inhibits basal TSH secretion as well as TSH response to iv TRH
      administration, a TSH secretory pattern similar to that noted at the peak of many
      nonthyroidal illnesses.

PMID- 8563479
TI  - Familial differentiated carcinoma of the thyroid: report of five pairs of
      siblings.

PMID- 8563480
TI  - Acquired von Willebrand's syndrome causing a hemorrhagic diathesis in a patient
      with hypothyroidism.
AB  - The occurrence of bleeding diathesis with menorrhagia and easy bruising may occur
      in patients with moderate to severe hypothyroidism sometimes linked to acquired
      von Willebrand's disease (VWD). We describe a patient with profound
      hypothyroidism in whom the diagnosis of hypothyroidism was established while
      evaluating uncontrolled gingival bleeding after a dental procedure. Thyroid
      hormone replacement led to a rise in von Willebrand factor, factor VIIIC, and a
      significant fall in the elevated bleeding time from 15 to 8 min. Acquired von
      Willebrand's disease is an unusual manifestation of hypothyroidism and is
      reversible.

PMID- 8563481
TI  - Rectal administration of iodide and propylthiouracil in the treatment of thyroid
      storm.
AB  - We administered potassium iodide and propylthiouracil per rectum, in conjunction
      with intravenous dexamethasone and propranolol, for emergent treatment of a
      patient in thyroid storm with small bowel obstruction. Shortly after initiation
      of this treatment, the patient successfully underwent two emergent surgical
      procedures for resection of an intestinal volvulus with advanced peritonitis.
      Serum levels of iodide and propylthiouracil showed substantial absorption of
      these drugs via the rectal route. Measurement of 24-h urinary-free iodide
      indicated that the bioavailability of potassium iodide delivered by retention
      enema was at least 40%. Parenteral iodide preparations have been unavailable in
      the past, and continue to be difficult to obtain emergently. Rectal
      administration of inorganic iodide is an effective, readily available and less
      expensive alternative to parenteral sodium iodide for patients in thyroid storm
      with upper gastrointestinal tract dysfunction.

PMID- 8563482
TI  - Medullary thyroid carcinoma: recent advances and management update.
AB  - Medullary thyroid carcinoma (MTC) is a malignancy of the thyroid C-cells that
      comprises 5-10% of all thyroid cancers. MTC occurs in both sporadic and familial
      forms, the latter making up 25% of all MTCs and being comprised of three distinct
      syndromes--multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine
      neoplasia type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC). To
      date, screening for MTC has been performed using the pentagastrin stimulation
      test, which is a provocative test for calcitonin release. Germline mutations in
      the RET protooncogene have been identified in families manifesting these
      syndromes and genetic screening of individuals at risk of one of these syndromes
      has become integral to their clinical management. The majority of the mutations
      associated with MEN 2A and FMTC are tightly clustered in a cysteine-rich region
      of the RET receptor. A single mutation associated with MEN 2B is in the the
      tyrosine kinase domain of the RET receptor. Somatic mutations have been
      identified in the tumor tissue of individuals with sporadic MTC and may prove to
      be helpful markers in discerning the hereditary or sporadic nature of the MTC.
      There is general agreement that the primary operation for MTC should include
      total thyroidectomy and central neck lymph node clearance. The role of
      microdissection for recurrent disease awaits longitudinal evaluation. External
      radiotherapy, radionuclide therapy, and chemotherapy may have a role in
      palliation, but have not been proven to have a curative value. Prognostic factors
      are discussed.

PMID- 8563483
TI  - Thyrotropic action of human chorionic gonadotropin.
AB  - Hyperthyroidism or increased thyroid function has been reported in many patients
      with trophoblastic tumors. In these cases, greatly increased human chorionic
      gonadotropin (hCG) levels and suppressed TSH levels suggest that hCG has
      thyrotropic activity. Recent investigations have clarified the structural
      homology not only in the hCG and TSH molecules but also in their receptors, and
      this homology suggests the basis for the reactivity of hCG with the TSH receptor.
      The clinical significance of the thyrotropic action of hCG is now also recognized
      in normal pregnancy and hyperemesis gravidarum. Highly purified hLH binds to
      recombinant hTSH receptor and is about 10 times as potent as purified hCG in
      increasing cAMP. The beta-subunits of hCG and hLH share 85% sequence identity in
      their first 114 amino acids but differ in the carboxy-terminal peptide because
      hCG beta contains a 31-amino acid extension (beta-CTP). A recombinant mutant hCG
      that lacks beta-CTP showed almost identical potency to LH on stimulation of
      recombinant hTSH receptor. If intact hCG were as potent as hLH in regard to its
      thyrotropic activity, most pregnant women would become thyrotoxic. One of the
      roles of the beta-CTP may be to prevent overt hyperthyroidism in the first
      trimester of pregnancy when a large amount of hCG is produced by the placenta.
      Nicked hCG preparations, obtained from patients with trophoblastic disease or by
      enzymatic digestion of intact hCG, showed approximately 1.5- to 2-fold
      stimulation of recombinant hTSH receptor compared with intact hCG. This suggests
      that the thyrotropic activity of hCG may be influenced by the metabolism of the
      hCG molecule itself. Deglycosylation and/or desialylation of hCG enhances its
      thyrotropic potency. Basic hCG isoforms with lower sialic acid content extracted
      from hydatidiform moles were more potent in activating adenylate cyclase, and
      showed high bioactivity/immunoactivity (B/I) ratio in CHO cells expressing human
      TSH receptors. This is consistent with the finding that the beta-CTP truncated
      hCG with higher thyrotropic potency is substantially deglycosylated and
      desialylated in the beta-subunit relative to intact hCG because all four O-linked
      glycosylation sites occur within the missing C-terminal extension. The
      desialylated hCG variant also interacts directly with recombinant hTSH receptors
      transfected into human thyroid cancer cells. There is thyroid-stimulating
      activity in sera of normal pregnant women, and this correlates with serum hCG
      levels. The thyroid gland of normal pregnant women may be stimulated by hCG to
      secrete slightly excessive quantities of T4 and induce a slight suppression of
      TSH, perhaps being about 1 mU/L less than nongravid levels, but not high enough
      to induce overt hyperthyroidism. Maternal thyroid glands may secrete more thyroid
      hormone during early pregnancy in response to the thyrotropic activity of hCG
      that overrides the normal operation of the hypothalamic-pituitary-thyroid
      feedback system. Biochemical hyperthyroidism associated with hyperemesis
      gravidarum has been attributed to hCG. In patients with hyperemesis gravidarum,
      thyrotropic in serum correlated with hCG immunoreactivity, and the severity of
      vomiting as indicated by clinical and biochemical parameters correlated with the
      degree of thyroid stimulation. To understand the thyrotropic action of hCG, it is
      necessary to know whether hCG activates the same domain of the TSH receptor as
      does TSH. The identification of the molecular structure of the hCG isoform with
      the highest thyrotropic potency will resolve the enigma of gestational
      thyrotoxicosis and the hyperthyroidism associated with trophoblastic disease and
      hCG-producing tumors.

PMID- 8563484
TI  - Glucocorticoid-induced modulation of cytokine secretion from normal and leukemic
      human myelomonocytic cells.
AB  - Since glucocorticoid effects on inflammatory processes may be mediated via
      modulation of cytokine release, different types of myelomonocytic cells were
      stimulated in vitro with lipopolysaccharide (50 ng/ml) or phorbol myristate
      acetate (25 ng/ml) plus the ionophore A23187, 2 x 10(-7) M, and release of
      interleukin (IL)-1 beta, IL-8 and tumor necrosis factor (TNF)-alpha was measured
      after 24 h by ELISA. Peripheral blood mononuclear cells from two allergic and two
      normal human donors released similarly large quantities of IL-8 and lower amounts
      of IL-1 beta and TNF-alpha. This also held for myelomonocytic cell lines, with
      THP-1 cells being most active, followed by U-937 and HL-60 cells. All potent
      glucocorticoids studied caused a dose-dependent inhibition of cytokine release
      from donor cells, being most marked for IL-1 beta and lowest for IL-8. Inhibition
      of cytokine release was also noted with U-937 cells, with clear differences in
      potency between the glucocorticoids, whereas release was enhanced in all
      experiments with THP-1 cells. These results were confirmed with Northern blot
      analysis. Modulating effects of glucocorticoids on cytokine release are thus
      complex, and are particularly dependent on the cell type studied.

PMID- 8563485
TI  - Aspergillosis in acute myelogenous leukemia.

PMID- 8563486
TI  - Morphological studies on avian spinal cord chimeras.
AB  - Spinal cord chimeras were constructed by orthotopic grafting of quail embryonal
      neutral folds, neural crest and neural tube into chicken embryos. The spinal cord
      xenografts were accepted for varying lengths of time, but most chimeras
      eventually rejected the quail transplant. This was associated with perivenular
      cuffing and demyelination with preservation of most neurons, as well as clinical
      neurological symptoms. Twenty-four chimeras were studied to delineate the time of
      first appearance of glial deposits of immunoglobulin and to identify the
      subpopulations of T cells in spinal cord infiltrates. The results suggested that
      deposits of immunoglobulins on glial elements preceded inflammatory cell
      infiltration. The perivenular cuffs consisted predominantly of T cells and showed
      a preponderance of CD8- over CD4-positive cells (CD4/CD8 ratios around 0.6).
      Further, CD4+ cells were found almost exclusively in the central portions of the
      infiltrate, with the periphery consisting almost only of CD8+ cells. The diffuse
      cellular infiltrate of the parenchyme contained T and plasma cells. The T cells
      were almost exclusively CD8+. Plasma cells were seen only at the outer borders of
      the cuffs and dispersed throughout the quail-derived spinal cord tissue. It
      seemed that rejection of quail-derived melanocytes in feathers ('quail-like
      feathers'), described by us earlier, often preceded neurological symptoms and
      showed a histopathological pattern comparable to spinal cord lesions, i.e.,
      predominantly perivascular cuffing. In preliminary studies, enhancement of
      disease by immunization with quail organ suspension and decreased intensity of
      disease by combined immunosuppressive treatment with FK 506 and cycylophosphamide
      were suggested. The data presented here are compatible with the hypothesis that
      rejection of CNS quail tissue by chimeras is preceded in the periphery by
      rejection of melanocytes in segments of skin and in feathers, and that the spinal
      cord rejection relies on xenoantibodies and on cytotoxic as well as delayed
      hypersensitivity-type T cells. Finally, these data strengthen the analogy between
      the histopathologic presentation and immune effector composition of the xenograft
      rejection lesions in the chimeras and the plaques seen in patients with multiple
      sclerosis.

PMID- 8563487
TI  - Antibodies to quail erythrocytes in quail-chicken spinal cord chimeras.
AB  - Quail-chicken spinal cord chimeras are a model for temporary acceptance followed
      by rejection of xenografts and also for demyelinating lesions of the central
      nervous system. The antiglobulin test with quail erythrocytes was employed to
      detect antibodies in sera of quail-chicken spinal cord chimeras. Sera of all 46
      chimeras tested gave positive results. In virtually all instances, antibodies
      were detected within 10 weeks after hatching and they persisted for all the
      observation time up to 8 months. The antibodies detected in these tests were
      directed against species antigens of the quail. They were apparently identical
      with xenoantibodies described in a previous study, which were detected by
      indirect immunofluorescence with quail tissue sections; on the other hand, mixed
      agglutination tests with quail embryonal cell monolayers employed previously had
      detected a broader spectrum of antibodies that did the antiglobulin tests with
      quail erythrocytes. The antiglobulin test with quail erythrocytes seems the most
      cost-efficient and convenient test to monitor xenoantibody formation in this
      animal model.

PMID- 8563488
TI  - Comparative analysis of the genes encoding group 3 allergens from
      Dermatophagoides pteronyssinus and Dermatophagoides farinae.
AB  - Group 3 allergens of the genus Dermatophagoides represent one of the major groups
      of house dust mite allergens. The cDNA sequence data for Der p 3, in combination
      with both N-terminal amino acid sequences and substrate affinity data, have
      confirmed that the group 3 allergens are trypsin-like proteases. Using the
      information from the Der p 3 P3WS1 cDNA clone, genes encoding both Der f3 and Der
      p 3 have now been amplified by the polymerase chain reaction and analysed. Two
      Der f3 clones and three Der p 3 genomic clones were sequenced. Each of the clones
      contained a single small intron and encoded a mature protein of 233 amino acids.
      The nucleotide sequence was identical for both Der f3 clones. There was 81%
      identity between the Der f3 sequence and the original Der p 3 P3WS1 clone. The
      calculated molecular weight of Der f3 was 25.27 kDa compared to 24.98 kDa for Der
      p 3. All the amino acid residues required for the catalytic activity and the
      substrate specificity were conserved between the two homologues. The coding
      sequences of two of the three Der p 3 genomic clones were identical to the
      original Der p 3 P3WS1 clone with the third having nucleotide changes resulting
      in four non-conservative amino acid substitutions in the mature protein. These
      substitutions resulted in a molecule with a slightly larger molecular weight and
      a more acidic pI value than the original Der p 3 clone. This third Der p 3
      genomic clone is, therefore, an isoform of the Der p 3 P3WS1 clone and is
      classified as an isovariant of the allergen. The nucleotide sequence data
      presented are the first reported for Der f 3. The Der f 3 gene, like the Der p 3
      gene, encoded a trypsin-like protease, but with a slightly larger molecular
      weight.

PMID- 8563489
TI  - Characterization of major allergens of Parietaria officinalis.
AB  - The major allergens of Parietaria officinalis were characterized with a panel of
      nine monoclonal antibodies (mAbs). The binding of mAbs and patients' IgE in
      Western blots revealed two proteins with similar molecular weights in the range
      of 8-10 kD. Analysis of the mAb-binding patterns in Western blots of P.
      officinalis extract under reducing and nonreducing conditions allows the mAbs to
      be divided into three different groups. mAbs of group I recognize the higher
      molecular-weight component (9.4 kD), mAbs of group II recognize the lower
      component (8.8 kD) and mAbs of group III recognize both proteins. A comparable
      mAb-binding pattern was observed with Western blots of Parietaria judaica. The
      mAbs were used for affinity purification of the corresponding proteins from a P.
      officinalis extract. The purified proteins obtained with mAbs of group I-III
      inhibit the binding of patients' IgE (serum pool) to a high degree, indicating
      that they posses the major IgE-reactive epitopes. The affinity-purified proteins
      were subjected to SDS-PAGE, blotted and immunologically stained by mAb binding.
      The results confirmed those obtained with the complete extracts. The N-terminal
      amino acid sequences of the blotted proteins were analyzed. The sequences of all
      the proteins contained highly conserved regions: GGVV (positions 4-7) and MPPLL
      (positions 11-15), alternating with highly variable regions (positions 1-3 for
      group II and 8-10 for group I). A specific group I sequence appears to be at
      position 1-3 with the amino acids APA and a specific group II sequence appears to
      be at position 8-10 with the amino acids GAL. It is possible that the two similar
      proteins are isoforms of Par o 1.

PMID- 8563490
TI  - Systemic complement system depletion does not inhibit cellular accumulation in
      antihistamine pretreated allergic guinea pig lung.
AB  - The present study was designed to determine if depletion of the complement system
      in the circulation with cobra venom factor (CVF) prevented the cellular
      infiltration in a guinea pig model of asthma. Guinea pigs were sensitized with
      ovalbumin (OA) alone or OA with complete Freund's adjuvant. Animals were
      pretreated with CVF and challenged with OA aerosol for 15 min in the presence of
      the antihistamine pyrilamine. Either 6 or 20 h later, bronchoalveolar lavage
      (BAL) was collected and the numbers of white blood cells and red blood cells and
      amount of protein were determined. In addition, eosinophil peroxidase and
      myeloperoxidase activity of the lavage and lung homogenate was measured as an
      indicator of eosinophil and neutrophil infiltration. Aerosol OA challenge caused
      cellular infiltration in the lung and BAL. CVF treatment did not inhibit the OA
      induced cellular infiltration but resulted in an enhanced accumulation of
      eosinophils 6 h after OA and increased protein in the lavage at 20 h after OA
      compared to animals not treated with CVF and challenged with OA. Total hemolytic
      complement activity in the serum was reduced by more than 98% and local
      complement activity (C3 in the BAL) by more than 95% by CVF treatment. However,
      after OA challenge in CVF-treated animals, the C3 content of the BAL was not
      different from control. Thus, leakage of plasma proteins or local synthesis of C3
      induced by OA was sufficient to maintain C3 at normal levels in the BAL despite
      drastic reductions in C3 in the circulation (> 98%) by CVF treatment. Our studies
      indicate that the systemic complement system is not essential for the cellular
      infiltration in this guinea pig model of asthma. Complement in local compartments
      may have an important role in inflammatory events in the lung. In addition,
      complement system depletion and/or activation may be an important determinant of
      the severity of a subsequent allergic reaction.

PMID- 8563491
TI  - Effects of thromboxane A2 receptor antagonist (Bay u 3405) on nasal symptoms
      after antigen challenge in sensitized guinea pigs.
AB  - To define the role of thromboxane A2 (TxA2) in allergic rhinitis, we examined the
      effects of the TxA2 receptor antagonist Bay u 3405 (1, 3 and 10 mg/kg, orally) on
      nasal symptoms, changes in total airway resistance (TAR), histamine
      hypersensitivity and eosinophil infiltration into the nasal mucosa induced by
      topical antigen challenge in actively sensitized guinea pigs. Nasal symptoms
      (number of sneezes and scratches) were significantly inhibited by pretreatment
      with Bay u 3405, in a dose-dependent manner. We noted a biphasic increase in TAR
      after antigen challenge. The first peak response of TAR (177.5 +/- 6.1%, mean +/-
      SE) was partially but significantly inhibited by Bay u 3405 at 10 mg/kg (142.8 +/
      4.3%, p < 0.01). The second peak response of TAR (181.0 +/- 13.4%) was also
      inhibited by Bay u 3405 at 3 mg/kg (120.3 +/- 3.1%) and 10 mg/kg (125.2 +/- 9.4%)
      (both, p < 0.01). The histamine hypersensitivity induced by antigen was inhibited
      by Bay u 3405 at 15 mg/kg (p < 0.05). Moreover, the mean eosinophil infiltration
      into the nasal mucosa induced by antigen (644.1 +/- 202.6/both sides of the nasal
      septum) was inhibited to 137.8 +/- 69.0 by Bay u 3405 at 10 mg/kg (p < 0.05). In
      conclusion, our results suggest that TxA2 may play an important role in allergic
      rhinitis in guinea pig models.

PMID- 8563492
TI  - Prevention of the development of immediate hypersensitivity and airway
      hyperresponsiveness following in vivo treatment with soluble IL-4 receptor.
AB  - The effects of local versus systemic treatment with soluble IL-4 receptors (sIL
      4R) were tested in a model of allergen-induced immediate hypersensitivity
      responses in BALB/c mice. Mice sensitized through the airways to ovalbumin (OVA)
      by ultrasonic nebulization once a week for 4 weeks developed increased serum anti
      OVA IgE and IgG1 antibody titers and these were accompanied by immediate-type
      skin test responses to the allergen. These responses were also associated with
      the development of increased airway responsiveness (AR) as monitored by
      electrical field stimulation of tracheal smooth muscle preparations in vitro.
      Sensitized mice, treated by intraperitoneal injections of sIL-4R (150
      micrograms/injection) administered in parallel to the sensitization protocol,
      developed significant suppression of anti-OVA IgE, anti-OVA IgG1 antibody
      production and of immediate cutaneous hypersensitivity responses. Airway
      responsiveness was normalized to some extent. Total IgE production was only
      slightly reduced. These effects were comparable to the findings following
      intraperitoneal injection of monoclonal anti-IL-4 antibody. Administration of sIL
      4R via the airways was also effective in inhibiting the development of immediate
      hypersensitivity responses, including IgE production, and was more potent in
      normalizing airway responsiveness. These effects were achieved at lower
      concentrations than needed for systemic treatment. These data suggest that
      delivery of sIL-4R via the airways can effectively modulate the development of
      immediate hypersensitivity and airway hyperresponsiveness in response to
      aerosolized allergen.

PMID- 8563493
TI  - MHC class II antigen expression is increased in different forms of urticaria.
AB  - Urticarial reactions encompass a variety of inflammatory and immunological
      reactions. In order to clarify specific aspects of these processes, we analyzed
      the distribution and sequential expression of major histocompatibility complex II
      (MHC class II) molecules in tissue sections from different types of whealing
      reactions. Using immunohistochemical techniques and monoclonal antibodies,
      expression of HLA-DR, HLA-DP, and HLA-DQ was examined on resident and
      infiltrating cells in different skin cell compartments, comparing early with
      longer-lasting wheals and lesional with uninvolved skin. Sequential biopsies were
      studied in cold urticaria (CU). No increase of MHC class II molecule expression
      was found in early prick test wheals to common inhalant allergens. In CU,
      however, sequential biopsies demonstrated an up-regulation of MHC class II
      molecules within 30 min after elicitation. This was more pronounced in longer
      lasting urticaria lesions of acute, chronic recurrent and delayed pressure
      urticaria, with HLA-DR and, to a lesser degree, HLA-DP and HLA-DQ being noted on
      cell infiltrates, on vascular endothelia and around nerves and sweat glands.
      Nonelesional skin in these types of urticaria also showed increased MHC class II
      expression. Longer-lasting urticarial wheals are thus associated with up
      regulation of MHC class II molecules on resident and infiltrating cells,
      suggesting an involvement of these molecules in the pathomechanisms of these
      types of urticarial lesions.

PMID- 8563494
TI  - Interleukin-8 in airway inflammation in patients with asthma and chronic
      obstructive pulmonary disease.
AB  - We have investigated whether IL-8 is present in airway secretions from patients
      with asthma and chronic obstructive pulmonary disease (COPD) to obtain
      information on its possible role in airway inflammation in obstructive airways
      disease. In the bronchoalveolar lavage fluid (BALF) from 11 clinically stable
      patients with asthma the levels of IL-8 were increased compared to 10 healthy
      subjects (median: controls 21.5 pg/ml, asthma 244 pg/ml: p < 0.005). In the
      patients with asthma the levels of IL-8 correlated with the percentage
      neutrophils in the BALF (r = 0.81; p < 0.001) and with a parameter of the
      permeability of the respiratory membrane, the quotient (alpha 2-macroglobulin in
      BALF)/(alpha 2-macroglobulin in serum) (r = 0.66; p < 0.025). In the sputum sol
      phase of 9 patients with symptomatic asthma the levels of IL-8 were lower than in
      9 patients with COPD (asthma: 6.4 ng/ml; COPD: 16.3 ng/ml; p < 0.02) and
      significantly correlated with those of neutrophilic myeloperoxidase (MPO; r =
      0.85; p < 0.005). The increased levels of IL-8 in the airway secretions from both
      patients with asthma and COPD may be markers of an ongoing inflammatory process,
      which is more pronounced in patients with COPD. In patients with asthma the
      strong correlation between the levels of IL-8 and the percentage neutrophils
      and/or the levels of MPO points to a role of IL-8 in the recruitment and
      activation of neutrophils in the airway lumen.

PMID- 8563495
TI  - Brugia malayi infection in mice with selective suppression of IgE production.
AB  - For the purpose of evaluating the roles of IgE in helminth infections in vivo,
      IgE-suppressed mice provide useful models. After infection with 50 third-stage
      larvae of the filarial parasite Brugia malayi, total IgE in BALB/c mice increased
      to five times higher than uninfected levels. However, anti-B. malayi IgE antibody
      was not detected, indicating polyclonal IgE B cell activation by the infection.
      In BALB/c mice which had received repeated injections of anti-mouse epsilon
      monoclonal antibody from birth and which were subsequently infected, total IgE
      levels were less than 10 ng/ml, but anti-B. malayi IgG antibody and total IgA
      were produced similar to the control. Therefore, IgE-isotype-specific suppression
      was attained. Concerning the protection against B. malayi, the numbers of fourth
      stage larvae and adult worms at 2 and 5 weeks after primary infection,
      respectively, and fourth-stage larvae at 2 weeks after secondary infection were
      not significantly different between control and IgE-suppressed mice.

PMID- 8563496
TI  - Systemic anaphylaxis after eating storage-mite-contaminated food.
AB  - We describe 2 cases in whom systemic anaphylaxis developed shortly after they had
      eaten food contaminated by a storage mite, Tyrophagus putrescentiae. We were able
      to demonstrate that these cases were sensitive to the storage mites but not to
      food allergens, leading us to conclude that the cases' anaphylactic episodes were
      the result of ingestion of the storage mites. This is the first report of the
      ingestion of storage mites causing systemic anaphylaxis in sensitive persons.

PMID- 8563497
TI  - Chemokines as mediators of allergic inflammation.
AB  - The selective distribution of reactive leukocytes to foci of inflammation or
      lymphoid organs is thought to rely on the generation of highly specific
      'attractive' forces which can enhance or subvert the physiological trafficking
      process. It is becoming increasingly apparent that the selective trafficking of
      leukocytes is governed by both the release of soluble mediators, or
      chemoattractants, as well as the matrix upon or through which the cells must
      traverse. A balance exists between endogenous cellular adhesion receptors (as
      well as extracellular matrix proteins) and other inducible adhesion receptors
      which can be up-regulated on this 'docking station'. This dynamic environment
      provides a prominent signal for leukocyte extravasation from the blood or lymph
      vessel lumenal surface through to the tissue space. This report reviews current
      thinking on the delicate interplay between a superfamily of chemoattractant
      cytokines, the chemokines, and the various classes of cellular adhesion
      molecules. In it we highlight the idea that the balance between basal and
      inducible regulators of cell adhesion and migration is critical. Should it be
      disrupted, the signals responsible for induction and maintenance of an
      inflammatory response and those responsible for its resolution become
      disregulated, resulting in inflammatory pathology.

PMID- 8563498
TI  - New approach to primary medical care. Nine-point plan based on flawed analysis.

PMID- 8563499
TI  - Facing ethical issues.

PMID- 8563500
TI  - Benzodiazepine debate continues.

PMID- 8563501
TI  - Thinking "green".

PMID- 8563502
TI  - Respecting patient consent.

PMID- 8563503
TI  - Dilemmas in care of the elderly.

PMID- 8563505
TI  - Continuity of care. Opportunity for residents to see repeat patients.
AB  - OBJECTIVE: To examine the opportunity for first-year family medicine residents to
      experience continuity of care during family medicine block time and half-day
      returns. DESIGN: Retrospective analysis of patient encounter data during the 1987
      1988 and 1991-1992 academic years to determine how much contact residents had
      with repeat patients. SETTING: Two family medicine teaching centres in Edmonton.
      PARTICIPANTS: First-year family medicine residents: 24 residents during 1987-1988
      and 24 during 1991-1992. MAIN OUTCOME MEASURES: Number of patient-resident
      contacts and number of repeat contacts. RESULTS: During the 4-month block time
      and half-day return, residents had repeat contact with 25.9% and 20.3% of the
      patients seen. These patients provided 48.3% and 37.7% of all visits at Centres A
      and B, respectively. CONCLUSION: Increasing block time from 2 to 4 months
      resulted in only a slight increase in repeat contact with patients. Half-day
      returns did not appear to enhance the opportunity for continuity of care.

PMID- 8563504
TI  - Asthma and chronic bronchitis. Can family physicians predict rates of
      progression?
AB  - OBJECTIVE: To investigate whether the progression rate of asthma or chronic
      bronchitis can be predicted from a cross-sectional assessment of features that
      can be measured by family physicians. DESIGN: Secondary analysis of data from a 2
      year randomized, controlled bronchodilator intervention study in family practice.
      SETTING: Twenty-nine general practices in the eastern part of The Netherlands.
      PATIENTS: One hundred sixty patients (101 with chronic bronchitis, 59 with
      asthma) from the 29 general practices. INTERVENTIONS: Predictors were related to
      the annual decline in lung function (the forced expiratory volume in one second)
      by means of multiple analysis of variance, controlling for age, sex, smoking
      habits, initial FEV1 level, bronchial hyperresponsiveness, reversibility of
      obstruction, and medication during the study. MAIN OUTCOME MEASURES: Predictors
      of the annual decline in lung function (FEV1), which is believed to be the most
      important measure for progression. RESULTS: Only three variables predicted the
      decline in lung function: having a barrel-shaped chest, experiencing wheezing,
      and an unusual diurnal peak-flow rate index. Wheezing was the best predictor of
      the annual decline in lung function. In chronic bronchitis, the decline in FEV1
      of wheezing patients was 133 mL/y compared with 62 mL/y for non-wheezing patients
      (P < 0.05). In asthma with more severe symptoms, wheezing patients had a tendency
      to decline 156 mL/y compared with 57 mL/y among non-wheezing patients (P = 0.08).
      CONCLUSIONS: It is nearly impossible to predict the progression rate of asthma or
      chronic bronchitis from symptoms, physical signs of the chest, and the PEFR.
      Therefore, patients with a rapid progression rate can probably be detected only
      by monitoring progression of the disease through repeated lung function testing.

PMID- 8563506
TI  - How well do family physicians manage sexually transmitted diseases?
AB  - OBJECTIVE: To identify gaps in knowledge about sexually transmitted diseases
      (STDs) and evaluate practice. DESIGN: We compared how 49 family physicians
      managed 249 episodes of STDs with the recommendations of the 1988-1989 Canadian
      STD management guidelines. (The study took place before revised guidelines were
      distributed in late 1992.) SETTING: Family physicians' practices throughout
      Canada. PARTICIPANTS: Physicians recruited by the National Research System from
      among the members of the College of Family Physicians of Canada. These physicians
      had been in practice for a mean of 9 years; 43 were Certificants of the College.
      MAIN OUTCOME MEASURES: Family physicians' self-reported episodes of sexually
      transmitted disease evaluated in light of current Canadian guidelines. RESULTS:
      Of the 249 episodes studied, 215 (86.3%) were treated effectively, and 34 (13.7%)
      were judged to have been treated ineffectively. Of the 215 effective treatments,
      67 (31.2%) were not completely in agreement with current guidelines. CONCLUSION:
      Experienced family physicians with postgraduate training usually manage STDs
      well. The number of ineffective treatments and effective treatments not following
      the 1988-1989 guidelines, especially for pelvic inflammatory disease, indicates
      that information on managing certain STDs and syndromes should be made available
      to all family physicians in a format that is easy to read and use.

PMID- 8563507
TI  - Exercise-induced asthma. What family physicians should do.
AB  - Exercise-induced asthma is described as a transitory increase in airway
      resistance during or after vigorous exercise. Nearly 90% of patients with chronic
      asthma and 40% of allergic nonasthmatic patients have the condition. Family
      physicians should try to educate patients about their asthma and, barring
      contraindications, encourage them to participate in regular physical activity.

PMID- 8563508
TI  - Emergency management of acute adult asthma.
AB  - Despite advances in understanding the pathophysiology of acute asthma and the
      development of new, effective therapies, patients still die. While physicians
      agree that most asthma deaths could be prevented if patients were treated
      adequately, evidence suggests that both patients and physicians continue to
      underestimate the severity of asthma attacks and delay adequate treatment.

PMID- 8563509
TI  - Glucocorticosteroid treatment of asthma.
AB  - Inhaled glucocorticoids are currently an important part of asthma management.
      There is no evidence that the more recently introduced inhaled agents, which have
      high topical activity and low systemic bioavailability, are unsafe at doses below
      2000 micrograms/d. The choice of the delivery device for inhaled
      glucocorticosteroids is as important as the choice of the particular drug.

PMID- 8563510
TI  - Management of gastrointestinal hemorrhage.
AB  - Acute gastrointestinal hemorrhage is a common problem that requires prompt
      recognition and management to prevent serious morbidity and mortality. Management
      goals are stabilization of the patient with vigorous fluid resuscitation followed
      by investigation and definitive treatment of the bleeding source. Endoscopy is
      often the initial diagnostic test and allows therapeutic measures to be performed
      at the same time.

PMID- 8563511
TI  - Urinary bladder rupture in an elderly patient: case report.
AB  - Urinary bladder rupture should be suspected in elderly patients with an acute
      abdomen. Because symptoms are often atypical among elderly patients, this
      condition is often undetected. Early diagnosis and treatment could help reduce
      the mortality rate associated with this condition.

PMID- 8563512
TI  - Asthma 1995. Willis's "terrible disease".

PMID- 8563513
TI  - Caring for children. Update on CICH activities. Canadian Institute of Child
      Health.

PMID- 8563514
TI  - Practically confidential. Legal and ethical dilemmas in practice.

PMID- 8563515
TI  - Retrospective. Part 2: Education.

PMID- 8563516
TI  - Platelet activation.
AB  - This review article describes the different receptors, second-messengers and
      mechanisms involved in platelet activation. Several platelet agonists have well
      defined receptors at the platelet membrane of which a number are single
      polypeptides with 7 hydrophobic transmembrane domains. These receptors are
      connected, via GTP regulatory proteins, with cytoplasmic second-messenger
      generating enzymes. Phospholipase C and adenylate cyclase are the two best-known
      enzymes, generating inositol triphosphate (IP3) and diacyl glycerol from
      phosphatidylinositol biphosphate and cyclic AMP from ATP respectively. The
      intraplatelet free calcium level, which is critical for the activation status of
      the platelet, is increased by IP3 and is lowered in the presence of rising cyclic
      AMP concentrations. Shape-change occurs with small increases in intraplatelet
      calcium, while aggregation and secretion of granules take place at higher
      calcium, levels. The role of myosin and actin filaments and of transmembrane
      glycoproteins is further discussed.

PMID- 8563517
TI  - Sickle cell disease and pregnancy.
AB  - Sickle cell disease refers to a group of genetic disorders characterised by the
      predominance of hemoglobin S. This includes sickle cell anemia (SS) sickle
      hemoglobin C disease (SC), sickle beta thalassemia plus (S beta + Thal), sickle
      beta thalassemia zero (beta zero Thal), sickle with alpha thalassemia (SS alpha
      Thal) and rare combinations of sickle hemoglobin with Hb D, Hb O, etc. While
      pregnancy does carry risk for the woman with sickle cell disease (SCD) and for
      the fetus, pregnancy can be well tolerated by the major genotypes. Infants born
      from these pregnancies may tend to be small for gestational age and undergo
      premature delivery. While complications for both sickle-related events and for
      pregnancy are seen, data to date state that women are able to complete their
      pregnancies successfully. Counselling, regular prenatal visits and aggressive
      treatment of acute events are always indicated. There is no proof that
      prophylactic transfusion alters the outcome of pregnancy. Transfusion therapy
      should be reserved for those patients with previous perinatal mortality, pre
      eclampsia, acute chest syndrome, new onset neurological event, severe anemia and
      in preparation for surgical intervention. Thus, blood transfusion will continue
      to have a role in management of obstetrical and medical indications accompanied
      by meticulous prenatal care and early detection of complications. In addition,
      newborn screening should be recommended for the early detection of infants with
      disease.

PMID- 8563518
TI  - Hereditary red cell enzymopathies.
AB  - The hereditary red cell enzymopathies are an uncommon but important cause of
      chronic haemolytic anaemia. Their clinical diversity is mirrored by increasingly
      evident heterogeneity at the molecular level. The structure, function, and
      expression of the genes encoding red cell enzymes and the nature of the gene
      defects in the deficient state are examined.

PMID- 8563519
TI  - Parvovirus B19 infection and hematopoiesis.
AB  - Parvovirus B19, the only known human pathogenic parvovirus, is highly tropic to
      human bone marrow and replicates only in erythroid progenitor cells. The basis of
      this erythroid tropism is the tissue distribution of the B19 cellular receptor,
      globoside (blood group P antigen). In individuals with underlying hemolytic
      disorders, infection with parvovirus B19 is the primary cause of transient
      aplastic crisis (TAC). In immunocompromised patients, persistent B19 infection
      may develop that manifests as pure red cell aplasia and chronic anemia. B19
      infection in utero can result in fetal death, hydrops fetalis, or congenital
      anemia. Diagnosis is based on examination of the bone marrow and B19 virological
      studies. Treatment of persistent infection with immunoglobulin leads to a rapid
      marked resolution of the anemia.

PMID- 8563520
TI  - Disorders of neutrophil function.
AB  - Major bacterial infections are most commonly associated with agranulocytosis or
      an abnormality of immunoglobulins or complement. Occasionally, repeated
      infections cannot be attributed to these relatively common causes. In such cases,
      a quantitative abnormality in neutrophil function should be sought. Complete
      evaluation of neutrophil function, including: chemotaxis, adhesion, aggregation,
      phagocytosis, granule content and degranulation, respiratory burst activity and
      bacterial killing is expensive and requires the services of a specialized
      laboratory. However, preliminary screening of a patient with a predisposition
      towards infection can be carried out using simple and inexpensive methods. These
      include examination of blood films, chemotaxis assay, NBT test and peroxidase
      staining. For final diagnosis and determination of genetic transmission and
      treatment, specific tests are indicated. Investigation of neutrophil functions
      may be useful for the diagnosis of congenital and acquired neutrophil disorders.
      These assays may also be useful in research, diagnosis and follow up of non
      infectious diseases with active inflammatory component.

PMID- 8563521
TI  - High-dose therapy for breast cancer.
AB  - The high incidence of breast cancer in young women, and the unfavorable prognosis
      for those who present with a high number of lymph nodes involved with cancer, has
      encouraged the development and evaluation of new treatment strategies. The use of
      dose intensification is supported by laboratory and clinical models. In this
      review article, the use of dose intensification supported by hemopoietic growth
      factors, and also by hemopoietic stem cells, is discussed. The results of
      published studies of high-dose chemotherapy in Stage II, III, and IV breast
      cancer are discussed and summarized, including those randomized comparisons with
      more conventional therapy. Improvements in supportive care continue to reduce the
      risks from neutropenia and thrombocytopenia, and these and other toxicities are
      likely to decrease as side-effects are anticipated and experience increases.

PMID- 8563522
TI  - Publishing research supported by the tobacco industry.

PMID- 8563523
TI  - Nursing shortages.

PMID- 8563524
TI  - Homicides and suicides by mentally ill people.

PMID- 8563525
TI  - Neonatal prevention of iron deficiency.

PMID- 8563526
TI  - The melanoma epidemic: reality and artefact.

PMID- 8563527
TI  - Minocycline for acne.

PMID- 8563528
TI  - Nursing shortfall hits Britain.

PMID- 8563529
TI  - Inadequate care linked to homicides and suicides.

PMID- 8563530
TI  - Doctors in Britain urged to practise effectively.

PMID- 8563531
TI  - Elderly in US have rising suicide risk.

PMID- 8563532
TI  - Survival outcome of care by specialist surgeons in breast cancer: a study of 3786
      patients in the west of Scotland.
AB  - OBJECTIVE: To compare survival outcome for patients with breast cancer cared for
      by specialist and non-specialist surgeons in a geographically defined area.
      DESIGN: Retrospective study of all female patients aged under 75 years in the
      area treated between 1980 and June 1988 (before breast screening began). Patients
      were identified from the cancer registry and from pathology records of all
      hospitals in the area. Specialist surgeons were identified by one author. All
      other surgeons caring for patients from the area were considered non-specialists.
      SETTING: A geographically defined population in urban west of Scotland. SUBJECTS:
      3786 patients with histologically verified breast cancer operated on between 1
      January 1980 and 30 June 1988 and followed to 31 December 1993. MAIN OUTCOME
      MEASURES: Five and 10 year survival rates for specialists and non-specialists;
      relative hazard ratios derived from Cox's proportional hazards model adjusted for
      prognostic factors--age, socioeconomic status, tumour size, and nodal
      involvement. RESULTS: The five year survival rate was 9% higher and the 10 year
      survival 8% higher for patients cared for by specialist surgeons. A reduction in
      risk of dying of 16% (95% confidence interval 6% to 25%) was found after
      adjustment for age, tumour size, socioeconomic status, and nodal involvement. The
      benefit of specialist care was apparent for all age groups, for small and large
      tumours, and for tumours that did and did not affect the nodes and was consistent
      across all socioeconomic categories. CONCLUSIONS: Survival differences of the
      magnitude demonstrated have implications for the provision of services for the
      treatment of women with breast cancer. There is a need to improve equity in the
      treatment of breast cancer.

PMID- 8563533
TI  - Prevention of respiratory complications after abdominal surgery: a randomised
      clinical trial.
AB  - OBJECTIVE: To evaluate the prevention of respiratory complications after
      abdominal surgery by a comparison of a global policy of incentive spirometry with
      a regimen consisting of deep breathing exercises for low risk patients and
      incentive spirometry plus physiotherapy for high risk patients. DESIGN:
      Stratified randomised trial. SETTING: General surgical service of an urban
      teaching hospital. PATIENTS: 456 patients undergoing abdominal surgery. Patients
      less than 60 years of age with an American Society of Anesthesia classification
      of 1 were considered to be at low risk. OUTCOME MEASURES: Respiratory
      complications were defined as clinical features consistent with collapse or
      consolidation, a temperature above 38 degrees C, plus either confirmatory chest
      radiology or positive results on sputum microbiology. We also recorded the time
      that staff devoted to prophylactic respiratory therapy. RESULTS: There was good
      baseline equivalence between the groups. The incidence of respiratory
      complications was 15% (35/231) for patients in the incentive spirometry group and
      12% (28/225) for patients in the mixed therapy group (P = 0.40; 95% confidence
      interval -3.6% to 9.0%). It required similar amounts of staff time to provide
      incentive spirometry and deep breathing exercises for low risk patients. The
      inclusion of physiotherapy for high risk patients, however, resulted in the
      utilisation of an extra 30 minutes of staff time per patient. CONCLUSIONS: When
      the use of resources is taken into account, the most efficient regimen of
      prophylaxis against respiratory complications after abdominal surgery is deep
      breathing exercises for low risk patients and incentive spirometry for high risk
      patients.

PMID- 8563534
TI  - Depression and other psychiatric morbidity in carers of elderly people living at
      home.
AB  - OBJECTIVE: To describe the mental health of a community sample of carers of
      elderly people with dementia, depression, or physical disability and to compare
      that with the mental health of other adults living in the household and of those
      living alone. DESIGN: Assessment of psychiatric morbidity and physical disability
      with standardised questionnaire in randomly selected enumeration districts;
      subjects were interviewed at home. SETTING: London Borough of Islington.
      SUBJECTS: 700 people aged > or = 65 and other coresidents. MAIN OUTCOME MEASURE:
      Depression measured with standardised interview. RESULTS: The prevalence of
      depression was not significantly higher in carers overall (15%) than in
      coresidents (11%). Being a woman carer was a significant predictor of psychiatric
      illness. Depression was more common in the carers of people with a psychiatric
      disorder than in coresidents (24% v 11%, P < 0.05) and in those living alone
      (19%). Depression was most common (47%) in women carers of people with dementia.
      CONCLUSION: The increase in psychiatric morbidity reported in carers of people
      with psychiatric disorders may reflect the lack of a confiding relationship.

PMID- 8563536
TI  - Changing patterns of invasive Haemophilus influenzae disease in England and Wales
      after introduction of the Hib vaccination programme.

PMID- 8563535
TI  - Fetal growth and cardiovascular risk factors in Jamaican schoolchildren.
AB  - OBJECTIVE: To determine relation between schoolchildren's blood pressure,
      glycated haemoglobin level, and cholesterol concentration and their
      anthropometry, socioeconomic status, and birth measurements. DESIGN:
      Retrospective cohort study. SETTING: 27 schools closest to University Hospital of
      the West Indies, Kingston, Jamaica. SUBJECTS: 2337 children aged 6-16 years who
      were born at university hospital were recruited, and their birth records were
      recovered: 1610 had suitable records, 659 had records including birth length, and
      610 of these were prepubertal. MAIN OUTCOME MEASURES: Blood pressure, glycated
      haemoglobin level, serum cholesterol concentration, anthropometry at birth,
      current anthropometry, and socioeconomic status. RESULTS: Multiple regression
      analysis showed that children's systolic blood pressure was inversely related to
      their birth weight (P < 0.0001) and directly related to their current weight.
      Glycated haemoglobin level was higher in children with thicker triceps skinfolds
      (P < 0.001) and who had been shorter at birth (P = 0.003). Serum cholesterol
      concentration was inversely related to current height (P = 0.001) and to length
      at birth (P = 0.09) and was directly related to triceps skinfold thickness and
      higher socioeconomic status (P < 0.001). CONCLUSIONS: Blood pressure in childhood
      was inversely related to birth weight and directly to current weight. Glycaemic
      control and serum cholesterol were related to short length at birth, height
      deficit in childhood, and childhood obesity.

PMID- 8563537
TI  - Congenital rubella in south India: diagnosis using saliva from infants with
      cataract.

PMID- 8563538
TI  - Alternatives to hospital care: what are they and who should decide?
AB  - OBJECTIVE: To examine potential for alternatives to care in hospitals for acute
      admissions, and to compare the decisions about these alternatives made by
      clinicians with different backgrounds. DESIGN: Standardised tool was used to
      identify patients who could potentially be treated in an alternative form of
      care. Information about such patients was assessed by three panels of clinicians:
      general practitioners without experience of general practitioner beds, general
      practitioners with experience of general practitioner beds, and consultants.
      SETTING: One hospital for acute admissions in a rural area of the South and West
      region of England. SUBJECTS: Of 620 patients admitted to specialties of general
      medicine and care of the elderly, details of 112 were assessed by panels. MAIN
      OUTCOME MEASURES: Proportion of hospitalised patients who could have received
      alternative care and identification of most appropriate alternative form of care.
      RESULTS: Both general practitioner panels estimated that between 51 and 89 of the
      hospitalised patients could have received alternative care (equivalent to 8-14%
      of all admissions). Consultants estimated that between 25 and 55 patients could
      have had alternative care (5.5-9% of all admissions). General practitioner bed
      and urgent outpatient appointment were the main alternatives chosen by all three
      panels. CONCLUSION: About 10% of admissions to general hospital might be suitable
      for alternative forms of care. Doctors with different backgrounds made similar
      overall assessments of most appropriate forms of care.

PMID- 8563539
TI  - Lessons for health care rationing from the case of child B.
AB  - More details have emerged about the child B leukaemia case with the publication
      of the All England Law Report on the Appeal Court decision. At the time the view
      was widely held that the controversy might have been avoided if the responsible
      health authority had consulted the public. The law report reveals, however, that
      the courts adopted a moral language widely at variance with that of the patient's
      doctor. The courts were concerned to support a utilitarian decision procedure
      based on calculations of the greatest overall good; the doctor was concerned with
      the best interests of a sick child. The doctor-patient relationship may be
      damaged when public consideration transforms the issue in this way. Also, the
      Appeal Court supported a decision which claimed to have "weighed" opposing
      evaluations, but it excused the health authority from describing how that
      weighing took place. One of the main criticisms of the utilitarian approach,
      however, is that weighing of this type is extremely difficult to justify. By its
      ruling the court has made legal challenge on the grounds of inadequate
      consultation virtually impossible to substantiate.

PMID- 8563540
TI  - Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like
      syndrome.
AB  - Monocycline is the most widely prescribed systemic antibiotic for acne largely
      because it needs to be given only once or twice a day and seems not to induce
      resistance. Up to April 1994 11 cases of minocycline induced systemic lupus
      erythematosus and 16 cases of hepatitis had been reported to the Committee on
      Safety of Medicines. An analysis of these cases together with seven other cases
      shows the severity of some of these reactions. Two patients died while taking the
      drug for acne and a further patient needed a liver transplant. Acne itself can
      induce arthritis and is often seen in association with autoimmine liver disease,
      but the clinical and biochemical resolution seen after withdrawal of the drug,
      despite deterioration of the acne, suggests a drug reaction. In five cases re
      exposure led to recurrence. Because reactions may be severe early recognition is
      important to aid recovery and also to avoid invasive investigations and
      treatments such as corticosteroids and immunosuppresants. Safer alternatives
      should be considered for treating acne.

PMID- 8563541
TI  - Allopurinol, erythema multiforme, and renal insufficiency.

PMID- 8563542
TI  - ABC of atrial fibrillation. Atrial fibrillation in general and hospital practice.

PMID- 8563543
TI  - Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Aetiology of
      scrapie in certain circumstances is not evidence against another aetiology in
      different circumstances.

PMID- 8563544
TI  - Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Magnetic
      resonance imaging may have a role in diagnosing Creutzfeldt-Jakob disease.

PMID- 8563545
TI  - Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Bovine spongiform
      encephalopathy is being maintained by vertical and horizontal transmission.

PMID- 8563547
TI  - Meat and Livestock Commission's advertising campaign. Commission defends
      campaign.

PMID- 8563546
TI  - Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Scrapie can be
      transmitted to mice by instillation of inoculum into the conjunctiva.

PMID- 8563548
TI  - Meat and Livestock Commission's advertising campaign. Commission emphasises
      nutritional value of meat in booklet for new mothers.

PMID- 8563549
TI  - Neonatal screening. Performance is hard to monitor.

PMID- 8563550
TI  - Treating anorexia nervosa. Patients' beliefs hinder treatment.

PMID- 8563551
TI  - Treating anorexia nervosa. Psychiatrists have mixed views on use of terminal care
      for anorexia nervosa.

PMID- 8563552
TI  - Neonatal screening. Pretest counselling and informed consent should be
      prerequisites.

PMID- 8563553
TI  - Pitfalls in the interpretation of tumour markers.

PMID- 8563554
TI  - Placebo controlled trials of ondansetron for postoperative nausea and vomiting.

PMID- 8563555
TI  - Risk factors for acanthamoeba keratitis.

PMID- 8563556
TI  - Deprivation payments should be based on enumeration districts.

PMID- 8563557
TI  - Community care and general practice. Focus should be put on barriers that hinder
      progress.

PMID- 8563558
TI  - Community care and general practice. Multidisciplinary, proactive care is needed.

PMID- 8563559
TI  - Emergency contraception. Care must be taken to ascertain that woman is not
      already pregnant.

PMID- 8563560
TI  - Public discussion of rationing decisions is essential.

PMID- 8563561
TI  - Emergency contraception. Use of the term is erroneous.

PMID- 8563562
TI  - Assessing the quality of care. Measuring the process of care is not always
      straightforward.

PMID- 8563563
TI  - Assessing the quality of care. Systematic methods must be used to develop review
      criteria.

PMID- 8563564
TI  - Contract minimum dataset includes confidential data.

PMID- 8563565
TI  - How to get patients' consent to enter clinical trials. Reports of trials should
      state proportion of people who refuse to participate.

PMID- 8563566
TI  - How to get patients consent to enter clinical trials. Information and consent
      forms should use short words and sentences.

PMID- 8563567
TI  - How to get patients consent to enter clinical trials. Participants should be
      given feedback about the trial.

PMID- 8563568
TI  - Nurses could halve GP workload.

PMID- 8563569
TI  - Training in substance abuse is lacking for GPs.

PMID- 8563570
TI  - Junior doctors' hours. Don't blame the Junior Doctors Committee.

PMID- 8563571
TI  - Junior doctors' hours. Shift work is poisoning juniors.

PMID- 8563572
TI  - Reporting poorly performing doctors may seem an expensive waste of time.

PMID- 8563573
TI  - Surprising new roles for endothelins.

PMID- 8563574
TI  - Genetic complexity in single gene diseases.

PMID- 8563575
TI  - Data protection, health care, and the new European directive.

PMID- 8563576
TI  - Thrombosis, phlebitis, and varicose veins.

PMID- 8563577
TI  - Children and sport.

PMID- 8563578
TI  - Shackling prisoners in hospital.

PMID- 8563579
TI  - Steep rise reported in meningococcal infections.

PMID- 8563580
TI  - Israel relaxes laws on food supplements.

PMID- 8563581
TI  - Scientists' new year: from dismal to delightful.

PMID- 8563582
TI  - Comparison of immunodeficiency and AIDS defining conditions in HIV negative and
      HIV positive men with haemophilia A.
AB  - OBJECTIVE: To investigate the hypothesis that high usage of clotting factor
      concentrate, rather than HIV infection, is the cause of immunodeficiency and AIDS
      in men with haemophilia. DESIGN: A comparison of AIDS defining conditions and CD4
      counts in HIV positive and HIV negative patients with haemophilia matched for
      usage of clotting factor concentrate. SETTING: A comprehensive care haemophilia
      centre. SUBJECTS: 17 HIV positive and 17 HIV negative male patients with
      haemophilia A (age range 12-60 at beginning of study period) who had received
      similar amounts of clotting factor concentrate yearly over the years 1980-90.
      MAIN OUTCOME MEASURES: Clinical events listed as AIDS defining in the Centers for
      Disease Control AIDS definition; CD4 lymphocyte counts; death. RESULTS: Of 108
      HIV positive male patients with haemophilia A, only 17 could be matched to an HIV
      negative patient. This was due to the much higher average usage of factor VIII in
      the HIV positive group. Between 1980 and 1990, 16 clinical events occurred in
      nine of the 17 HIV positive patients. No event occurred in the 17 HIV negative
      patients. In each pair the mean CD4 count during follow up was, on average, 0.5 x
      10(9)/l lower in the HIV positive patient. CONCLUSION: These data reject the
      hypothesis that high usage of clotting factor concentrate, rather than HIV
      infection, is the cause of immunodeficiency and AIDS in men with haemophilia.

PMID- 8563583
TI  - Commentary: non-HIV hypotheses must be studied more carefully.

PMID- 8563584
TI  - Response: arguments contradict the "foreign protein-zidovudine" hypothesis.

PMID- 8563585
TI  - Magnitude of benefit from earlier thrombolytic treatment in acute myocardial
      infarction: new evidence from Grampian region early anistreplase trial (GREAT)
AB  - OBJECTIVE: To generalise from the results of the Grampian region early
      anistreplase trial (GREAT) and to express the benefit of earlier thrombolysis in
      terms of lives saved per hour of earlier treatment. DESIGN: Multivariate analysis
      of a randomised double blind trial. SETTING: 29 rural practices in Grampian
      region and teaching hospitals in Aberdeen. SUBJECTS: 311 patients with suspected
      acute myocardial infarction and without contraindications to thrombolysis who
      were seen by their general practitioners within four hours of the start of
      symptoms. INTERVENTIONS: Anisterplase 30 units given intravenously, either by
      general practitioners before hospitalisation or later in hospital. MAIN OUTCOME
      MEASURE: Death within 30 months of entry into trial. RESULTS: Death within 30
      months was positively related to age (P < 0.0001) and to delay between start of
      symptoms and thrombolytic treatment (P = 0.0004). However, the probability of
      dying rose exponentially with earlier presentation, so death within 30 months was
      negatively related to the logarithm of the time of randomisation (P = 0.0163). In
      patients presenting two hours after start of symptoms each hour's delay in
      receiving thrombolysis led to the loss of 21 lives per 1000 within 30 days (95%
      confidence interval 1 to 94 lives per 1000) (P = 0.03) and 69 lives per 1000
      within 30 months (16 to 141 lives per 1000) (P = 0.0004). CONCLUSIONS: The
      magnitude of the benefit from earlier thrombolysis is such that giving
      thrombolytic treatment to patients with acute myocardial infarction should be
      accorded the same degree of urgency as the treatment of cardiac arrest.

PMID- 8563586
TI  - Benefit from earlier thrombolytic therapy is certain, but what is the magnitude
      of benefit?

PMID- 8563587
TI  - Outlook for survivors of childhood in sub-Saharan Africa: adult mortality in
      Tanzania. Adult Morbidity and Mortality Project.
AB  - OBJECTIVE: To measure age and sex specific mortality in adults (15-59 years) in
      one urban and two rural areas of Tanzania. DESIGN: Reporting of all deaths
      occurring between 1 June 1992 and 31 May 1995. SETTING: Eight branches in Dar es
      Salaam (Tanzania's largest city), 59 villages in Morogoro rural district (a poor
      rural area), and 47 villages in Hai district (a more prosperous rural area).
      SUBJECTS: 40,304 adults in Dar es Salaam, 69,964 in Hai, 50,465 in Morogoro
      rural. MAIN OUTCOME MEASURES: Mortality and probability of death between 15 and
      59 years of age (45Q15). RESULTS: During the three year observation period a
      total of 4929 deaths were recorded in adults aged 15-59 years in all areas. Crude
      mortalities ranged from 6.1/1000/year for women in Hai to 15.9/1000/year for men
      in Morogoro rural. Age specific mortalities were up to 43 times higher than rates
      in England and Wales. Rates were higher in men at all ages in the two rural areas
      except in the age group 25 to 29 years in Hai and 20 to 34 years in Morogoro
      rural. In Dar es Salaam rates in men were higher only in the 40 to 59 year age
      group. The probability of death before age 60 of a 15 year old man (45Q15) was
      47% in Dar es Salaam, 37% in Hai, and 58% in Morogoro; for women these figures
      were 45%, 26%, and 48%, respectively. (The average 45Q15s for men and women in
      established market economies are 15% and 7%, respectively.) CONCLUSION: Survivors
      of childhood in Tanzania continue to show high rates of mortality throughout
      adult life. As the health of adults is essential for the wellbeing of young and
      old there is an urgent need to develop policies that deal with the causes of
      adult mortality.

PMID- 8563588
TI  - Low serum cholesterol concentration and serotonin metabolism in men.

PMID- 8563589
TI  - Value of the electrocardiogram in identifying heart failure due to left
      ventricular systolic dysfunction.

PMID- 8563590
TI  - Management of labour in an isolated rural maternity hospital.
AB  - OBJECTIVES: To evaluate the use of a maternity unit run by general practitioners
      and midwives, describing the outcome of labour in an unselected group of women
      and quantifying the contribution made by general practitioners. DESIGN:
      Retrospective population based review of obstetric patients who had access to an
      isolated rural maternity unit. SETTING: Rural area 120 km from a consultant
      maternity unit. SUBJECTS: 997 consecutive women delivered between January 1987
      and May 1991. MAIN OUTCOME MEASURES: Mode of delivery and complications by place
      of booking and place of delivery; need for medical intervention and transfer.
      RESULTS: 530 women (53%) were booked for delivery in the rural unit; this group
      had a caesarean section rate of 3.8% and an unplanned transfer rate of 12.8% to
      the consultant unit in labour. Of the 462 who delivered in the low risk unit, 25
      (5%) required a forceps delivery; postnatal complications requiring emergency
      medical support occurred in a further 33 (7%). CONCLUSIONS: Risk characterisation
      is possible, but medical support from general practitioners and obstetricians is
      required in almost a third of women at low risk for complications of delivery.
      Results of this study support the team approach to obstetric management but not
      the move towards isolated units without organised medical support.

PMID- 8563592
TI  - Redesigning the journal: having your say.

PMID- 8563591
TI  - Vascular dementia.

PMID- 8563593
TI  - ABC of general surgery in children. Surgically correctable causes of vomiting in
      infancy.

PMID- 8563594
TI  - Altruism by proxy: volunteering children for bone marrow donation.

PMID- 8563595
TI  - False localising signs in the spinal cord.

PMID- 8563596
TI  - Tropical medicine for the 21st century. Tropical medicine should be concerned
      with medical problems endemic to the tropics.

PMID- 8563597
TI  - Tropical medicine for the 21st century. Tropical medicine should become specialty
      of "health in developing countries".

PMID- 8563598
TI  - Tropical medicine for the 21st century. Clinical care in resource poor countries
      is often provided by people outside the medical establishment.

PMID- 8563599
TI  - Tropical medicine for the 21st century. Genitourinary medicine should remain a
      separate specialty.

PMID- 8563600
TI  - Videotaping of general practice consultations.

PMID- 8563601
TI  - Chemotherapy in non-small cell lung cancer. Large trial will reduce uncertainty.
      Steering Committee of the Big Lung Trial.

PMID- 8563602
TI  - Allocating census data to general practice populations.

PMID- 8563603
TI  - Chemotherapy in non-small cell lung cancer. It may not be ethical to ask patients
      to participate in future trials.

PMID- 8563604
TI  - Chemotherapy in non-small cell lung cancer. Quality of life was ignored in meta
      analysis.

PMID- 8563605
TI  - Learning from primary care in developing countries. Innovations in developing
      countries have had worldwide relevance.

PMID- 8563606
TI  - Learning from primary care in developing countries. Authors overestimate role of
      barefoot doctors in China.

PMID- 8563607
TI  - Learning from primary care in developing countries. Outreach programme in Kenya
      was based on extensive community participation.

PMID- 8563608
TI  - Association of Helicobacter pylori infection with coronary heart disease. Study
      shows association between H pylori infection and hypertension.

PMID- 8563609
TI  - Association of Helicobacter pylori infection with coronary heart disease.
      Association may not be causal.

PMID- 8563610
TI  - Association of Helicobacter pylori infection with coronary heart disease. Study
      confirms previous findings.

PMID- 8563611
TI  - Association of Helicobacter pylori infection with coronary heart disease.
      Eradication of the infection on grounds of cardiovascular risk is not supported
      by current evidence.

PMID- 8563612
TI  - Increasing prescription of drugs for secondary prevention of myocardial
      infarction. Authors' recommendations are too restrictive.

PMID- 8563613
TI  - Increasing prescription of drugs for secondary prevention of myocardial
      infarction. Lipid lowering drugs should be considered too.

PMID- 8563614
TI  - Managing cleft lip and palate.

PMID- 8563615
TI  - Risk of breast cancer is also increased among Danish female airline cabin
      attendants.

PMID- 8563616
TI  - Effect of intensive treatment in insulin dependent diabetes mellitus with
      microalbuminuria. Sample size was too small.

PMID- 8563617
TI  - Effect of intensive treatment in insulin dependent diabetes mellitus with
      microalbuminuria. Work in non-insulin diabetes corroborates study's findings.

PMID- 8563618
TI  - Effect of intensive treatment in insulin dependent diabetes mellitus with
      microalbuminuria. Interpretation of study's results is open to criticism.

PMID- 8563619
TI  - Electronic mail may infect computers with viruses.

PMID- 8563620
TI  - Side-chain conformational entropy in protein folding.
AB  - An important, but often neglected, contribution to the thermodynamics of protein
      folding is the loss of entropy that results from restricting the number of
      accessible side-chain conformers in the native structure. Conformational entropy
      changes can be found by comparing the number of accessible rotamers in the
      unfolded and folded states, or by estimating fusion entropies. Comparison of
      several sets of results using different techniques shows that the mean
      conformational free energy change (T delta S) is 1 kcal.mol-1 per side chain or
      0.5 kcal.mol-1 per bond. Changes in vibrational entropy appear to be negligible
      compared to the entropy change resulting from the loss of accessible rotamers.
      Side-chain entropies can help rationalize alpha-helix propensities, predict
      protein/inhibitor complex structures, and account for the distribution of side
      chains on the protein surface or interior.

PMID- 8563621
TI  - The Alacoil: a very tight, antiparallel coiled-coil of helices.
AB  - The Alacoil is an antiparallel (rather than the usual parallel) coiled-coil of
      alpha-helices with Ala or another small residue in every seventh position,
      allowing a very close spacing of the helices (7.5-8.5 A between local helix
      axes), often over four or five helical turns. It occurs in two distinct types
      that differ by which position of the heptad repeat is occupied by Ala and by
      whether the closest points on the backbone of the two helices are aligned or are
      offset by half a turn. The aligned, or ROP, type has Ala in position "d" of the
      heptad repeat, which occupies the "tip-to-tip" side of the helix contact where
      the C alpha-C beta bonds point toward each other. The more common offset, or
      ferritin, type of Alacoli has Ala in position "a" of the heptad repeat (where the
      C alpha-C beta bonds lie back-to-back, on the "knuckle-touch" side of the helix
      contact), and the backbones of the two helices are offset vertically by half a
      turn. In both forms, successive layers of contact have the Ala first on one and
      then on the other helix. The Alacoil structure has much in common with the coiled
      coils of fibrous proteins or leucine zippers: both are alpha-helical coiled
      coils, with a critical amino acid repeated every seven residues (the Leu or the
      Ala) and a secondary contact position in between. However, Leu zippers are
      between aligned, parallel helices (often identical, in dimers), whereas Alacoils
      are between antiparallel helices, usually offset, and much closer together. The
      Alacoil, then, could be considered as an "Ala anti-zipper." Leu zippers have a
      classic "knobs-into-holes" packing of the Leu side chain into a diamond of four
      residues on the opposite helix; for Alacoils, the helices are so close together
      that the Ala methyl group must choose one side of the diamond and pack inside a
      triangle of residues on the other helix. We have used the ferritin-type Alacoil
      as the basis for the de novo design of a 66-residue, coiled helix hairpin called
      "Alacoilin." Its sequence is: cmSPDQWDKE AAQYDAHAQE FEKKSHRNng TPEADQYRHM ASQY
      QAMAQK LKAIANQLKK Gsetcr (with "a" heptad positions underlined and nonhelical
      parts in lowercase), which we will produce and test for both stability and
      uniqueness of structure.

PMID- 8563622
TI  - Structure comparison of native and mutant human recombinant FKBP12 complexes with
      the immunosuppressant drug FK506 (tacrolimus).
AB  - The consequences of site-directed mutagenesis experiments are often anticipated
      by empirical rules regarding the expected effects of a given amino acid
      substitution. Here, we examine the effects of "conservative" and
      "nonconservative" substitutions on the X-ray crystal structures of human
      recombinant FKBP12 mutants in complex with the immunosuppressant drug FK506
      (tacrolimus). R42K and R42I mutant complexes show 110-fold and 180-fold decreased
      calcineurin (CN) inhibition, respectively, versus the native complex, yet retain
      full peptidyl prolyl isomerase (PPIase) activity, FK506 binding, and FK506
      mediated PPIase inhibition. Interestingly, the structure of the R42I mutant
      complex is better conserved than that of the R42K mutant complex when compared to
      the native complex structure, within both the FKBP12 protein and FK506 ligand
      regions of the complexes, and with respect to temperature factors and RMS
      coordinate differences. This is due to compensatory interactions mediated by two
      newly ordered water molecules in the R42I complex structure, molecules that act
      as surrogates for the missing arginine guanidino nitrogens of R42. The absence of
      such surrogate solvent interactions in the R42K complex leads to some disorder in
      the so-called "40s loop" that encompasses the substituent. One rationalization
      proposed for the observed loss in CN inhibition in these R42 mutant complexes
      invokes indirect effects leading to a misorientation of FKBP12 and FK506
      structural elements that normally interact with calcineurin. Our results with the
      structure of the R42I complex in particular suggest that the observed loss of CN
      inhibition might also be explained by the loss of a specific R42-mediated
      interaction with CN that cannot be mimicked effectively by the solvent molecules
      that otherwise stabilize the conformation of the 40s loop in that structure.

PMID- 8563623
TI  - Covariation of residues in the homeodomain sequence family.
AB  - Homeodomains are 60 amino acid DNA binding domains found in numerous eukaryotic
      transcription factors. The homeodomain family is a useful system for studying
      sequence-structure relationships because several hundred sequences are known and
      the structures of several homeodomains have been determined. Covariation of amino
      acid residues in the homeodomain family has been investigated to see whether
      strongly covariant residue pairs can be understood in terms of the structure and
      function of these domains. Among 16 strongly covariant pairs examined, 2 are
      explained by the ability to form salt bridges, and 9 appear related to the DNA
      binding function of the proteins. For the remaining 5 pairs, the rationale for
      covariance remains unclear and the likelihood of artifactual correlations is
      discussed in the context of experimental and evolutionary biases in the selection
      of sequences. No significant correlation was found between covariance and
      structural proximity in the hydrophobic core.

PMID- 8563624
TI  - Drosophila engrailed-1,10-phenanthroline chimeras as probes of homeodomain-DNA
      complexes.
AB  - We have converted the Drosophila engrailed homeodomain into a sequence-specific
      nuclease by linking the protein to the chemical nuclease 1,10-phenanthroline
      copper (OP-Cu). Unique cysteines were introduced at six positions into the
      homeodomain by site-directed mutagenesis for the covalent attachment of OP-Cu.
      The varied DNA-binding affinity and specificity of these mutants and the DNA
      cleavage pattern of their OP-Cu derivatives allowed us to assess the crystal
      structure of the engrailed homeodomain-DNA complex. We have also achieved site
      specific double-stranded DNA scission with one of the homeodomain mutants, E28C,
      which has the potential of being used to identify engrailed binding sites in the
      genome. Because the homeodomain is so well conserved among members of the
      homeodomain-containing protein family, other homeodomain proteins can be
      converted into nucleases by attaching OP-Cu at position 28 of their homeodomains.

PMID- 8563625
TI  - Comparison of the accuracy of protein solution structures derived from
      conventional and network-edited NOESY data.
AB  - Network-editing experiments are variants of the basic NOESY experiment that allow
      more accurate direct measurement of interproton distances in macromolecules by
      defeating specific spin-diffusion pathways. Two network-editing approaches, block
      decoupled NOESY and complementary-block-decoupled-NOESY, were applied as three
      dimensional, heteronuclear-edited experiments to distance measurement in a small
      protein, turkey ovomucoid third domain (OMTKY3). Two-hundred and twelve of the
      original 655 distance constraints observed in this molecule (Krezel AM et al.,
      1994, J Mol Biol 242:203-214) were improved by their replacement by distances
      derived from network-edited spectra, and distance geometry/simulated annealing
      solution structure calculations were performed from both the unimproved and
      improved distance sets. The resulting two families of structures were found to
      differ significantly, the most important differences being the hinge angle of a
      beta-turn and an expansion of the sampled conformation space in the region of the
      reactive-site loop. The structures calculated from network-editing data are
      interpreted as a more accurate model of the solution conformation of OMTKY3.

PMID- 8563626
TI  - The use of side-chain packing methods in modeling bacteriophage repressor and cro
      proteins.
AB  - In recent years, it has been repeatedly demonstrated that the coordinates of the
      main-chain atoms alone are sufficient to determine the side-chain conformations
      of buried residues of compact proteins. Given a perfect backbone, the side-chain
      packing method can predict the side-chain conformations to an accuracy as high as
      1.2 A RMS deviation (RMSD) with greater than 80% of the chi angles correct.
      However, similarly rigorous studies have not been conducted to determine how well
      these apply, if at all, to the more important problem of homology modeling per
      se. Specifically, if the available backbone is imperfect, as expected for
      practical application of homology modeling, can packing constraints alone achieve
      sufficiently accurate predictions to be useful? Here, by systematically applying
      such methods to the pairwise modeling of two repressor and two cro proteins from
      the closely related bacteriophages 434 and P22, we find that when the backbone
      RMSD is 0.8 A, the prediction on buried side chain is accurate with an RMS error
      of 1.8 A and approximately 70% of the chi angles correctly predicted. When the
      backbone RMSD is larger, in the range of 1.6-1.8 A, the prediction quality is
      still significantly better than random, with RMS error at 2.2 A on the buried
      side chains and 60% accuracy on chi angles. Together these results suggest the
      following rules-of-thumb for homology modeling of buried side chains. When the
      sequence identity between the modeled sequence and the template sequence is > 50%
      (or, equivalently, the expected backbone RMSD is < 1 A), side-chain packing
      methods work well. When sequence identity is between 30-50%, reflecting a
      backbone RMS error of 1-2 A, it is still valid to use side-chain packing methods
      to predict the buried residues, albeit with care. When sequence identity is below
      30% (or backbone RMS error greater than 2 A), the backbone constraint alone is
      unlikely to produce useful models. Other methods, such as those involving the use
      of database fragments to reconstruct a template backbone, may be necessary as a
      complementary guide for modeling.

PMID- 8563627
TI  - Fluorescence of native single-Trp mutants in the lactose permease from
      Escherichia coli: structural properties and evidence for a substrate-induced
      conformational change.
AB  - Six single-Trp mutants were engineered by individually reintroducing each of the
      native Trp residues into a functional lactose permease mutant devoid of Trp (Trp
      less permease; Menezes ME, Roepe PD, Kaback HR, 1990, Proc Natl Acad Sci USA
      87:1638-1642), and fluorescent properties were studied with respect to solvent
      accessibility, as well as alterations produced by ligand binding. The emission of
      Trp 33, Trp 78, Trp 171, and Trp 233 is strongly quenched by both acrylamide and
      iodide, whereas Trp 151 and Trp 10 display a decrease in fluorescence in the
      presence of acrylamide only and no quenching by iodide. Of the six single-Trp
      mutants, only Trp 33 exhibits a significant change in fluorescence (ca. 30%
      enhancement) in the presence of the substrate analog beta,D-galactopyranosyl 1
      thio-beta,D-galactopyranoside (TDG). This effect was further characterized by
      site-directed fluorescent studies with purified single-Cys W33-->C permease
      labeled with 2-(4'-maleimidylanilino)-naphthalene-6-sulfonic acid (MIANS).
      Titration of the change in the fluorescence spectrum reveals a 30% enhancement
      accompanied with a 5-nm blue shift in the emission maximum, and single
      exponential behavior with an apparent KD of 71 microM. The effect of substrate
      binding on the rate of MIANS labeling of single-Cys 33 permease was measured in
      addition to iodide and acrylamide quenching of the MIANS-labeled protein.
      Complete blockade of labeling is observed in the presence of TDG, as well as a
      30% decrease in accessibility to iodide with no change in acrylamide quenching.
      Overall, the findings are consistent with the proposal (Wu J, Frillingos S,
      Kaback HR, 1995a, Biochemistry 34:8257-8263) that ligand binding induces a
      conformational change at the C-terminus of helix I such that Pro 28 and Pro 31,
      which are on one face, become more accessible to solvent, whereas Trp 33, which
      is on the opposite face, becomes less accessible to the aqueous phase. The
      findings regarding accessibility to collisional quenchers are also consistent
      with the predicted topology of the six native Trp residues in the permease.

PMID- 8563628
TI  - Two steps in the transition between the native and acid states of bovine alpha
      lactalbumin detected by circular polarization of luminescence: evidence for a
      premolten globule state?
AB  - A few studies indirectly support the existence of an intermediate in the
      transition of Ca(2+)-saturated bovine alpha-lactalbumin (alpha-LA) from the
      native (N) to the acidic (A) state, known as the molten globule state. However,
      direct experimental evidence for the appearance of this intermediate has not been
      obtained. The signal of circular polarization of luminescence (CPL) is sensitive
      to fine conformational transitions because of its susceptibility to changes in
      the environmental asymmetry of fluorescent chromophores in their excited
      electronic states. In the present study, CPL measurements were applied using the
      intrinsic tryptophan fluorescence of alpha-LA as well as the fluorescence of 8
      anilino-1-naphthalenesulfonic acid (ANS) bound to alpha-LA. CPL of tryptophan and
      ANS was measured in the pH range of 2.5-6 in order to find direct experimental
      evidence for the proposed intermediate. CPL (characterized by the emission
      anisotropy factor, g(em)) depends on the asymmetry of the protein molecular
      structure in the environment of the tryptophan and the ANS chromophores in the
      excited electronic state. The pH dependence of both the gab, absorption
      anisotropy factor determined by CD, and the ANS steady state fluorescence, showed
      a single transition at pH 3-3.7 as already reported elsewhere. This transition
      was interpreted as being a result of a change of the alpha-LA tertiary structure,
      which resulted in a loss of asymmetry of the environment of both the tryptophan
      residues and the ANS hydrophobic binding sites. The pH dependence of the
      tryptophan and ANS g(em) showed an additional conformational transition at pH 4
      5, which coincided with the pKa of Ca2+ dissociation (pKa 5), as predicted by
      Permyakov et al. (1981, Biochem Biophys Res Commun 100:191-197). The titration
      curve showed that there is a pH range between 3.7 and 4.1 in which alpha-LA
      exists in an intermediate state between the N- and A-state. We suggest that the
      intermediate is the premolten globule state characterized by a reduced Ca2+
      binding to the alpha-LA, native-like tertiary structure, and reduced asymmetric
      fluctuation of the tertiary structure on the nanosecond time scale. This
      intermediate resembles the "critical activated state" theoretically deduced by
      Kuwajima et al. (1989, J Mol Biol 206:547-561). The present study demonstrates
      the power of CPL measurements for the investigation of folding/unfolding
      transitions in proteins.

PMID- 8563629
TI  - Crystal structure of the dipeptide binding protein from Escherichia coli involved
      in active transport and chemotaxis.
AB  - The Escherichia coli periplasmic dipeptide binding protein functions in both
      peptide transport and taxis toward peptides. The structure of the dipeptide
      binding protein in complex with Gly-Leu (glycyl-L-leucine) has been determined at
      3.2 A resolution. The binding site for dipeptides is designed to recognize the
      ligand's backbone while providing space to accommodate a variety of side chains.
      Some repositioning of protein side chains lining the binding site must occur when
      the dipeptide's second residue is larger than leucine. The protein's fold is very
      similar to that of the Salmonella typhimurium oligopeptide binding protein, and a
      comparison of the structures reveals the structural basis for the dipeptide
      binding protein's preference for shorter peptides.

PMID- 8563630
TI  - Modeling of the structure of the Haemophilus influenzae heme-binding protein
      suggests a mode of heme interaction.
AB  - The structure and function of the periplasmic heme-binding protein HbpA of
      Haemophilus influenzae were investigated. This protein is involved in the import
      of heme into the bacteria through the inner membrane, and thus is a key element
      of the organism's ability to survive in blood. A high degree of sequence
      similarity between HbpA and the dipeptide-binding protein of Escherichia coli is
      suggested to be the result of a functional relationship. An HbpA model built
      using the dipeptide-binding protein suggests a mode of heme binding that is
      distinct from those known in proteins of the human host. These results provide a
      starting point for rational drug design.

PMID- 8563631
TI  - Homology modeling and molecular dynamics simulation of human prothrombin fragment
      1.
AB  - The crystallographic structure of bovine prothrombin fragment 1 bound with
      calcium ions was used to construct the corresponding human prothrombin structure
      (hf1/Ca). The model structure was refined by molecular dynamics to estimate the
      average solution structure. Accommodation of long-range ionic forces was
      essential to reach a stable solution structure. The gamma-carboxyglutamic acid
      (Gla) domain and the kringle domain of hf1/Ca independently equilibrated.
      Likewise, the hydrogen bond network and the calcium ion coordinations were well
      preserved. A discussion of the phospholipid binding of the vitamin K-dependent
      coagulation proteins in the context of the structure and mutational data of the
      Gla domain is presented.

PMID- 8563633
TI  - Discovery of the ammonium substrate site on glutamine synthetase, a third cation
      binding site.
AB  - Glutamine synthetase (GS) catalyzes the ATP-dependent condensation of ammonia and
      glutamate to yield glutamine, ADP, and inorganic phosphate in the presence of
      divalent cations. Bacterial GS is an enzyme of 12 identical subunits, arranged in
      two rings of 6, with the active site between each pair of subunits in a ring. In
      earlier work, we have reported the locations within the funnel-shaped active site
      of the substrates glutamate and ATP and of the two divalent cations, but the site
      for ammonia (or ammonium) has remained elusive. Here we report the discovery by X
      ray crystallography of a binding site on GS for monovalent cations, Tl+ and Cs+,
      which is probably the binding site for the substrate ammonium ion. Fourier
      difference maps show the following. (1) Tl+ and Cs+ bind at essentially the same
      site, with ligands being Glu 212, Tyr 179, Asp 50', Ser 53' of the adjacent
      subunit, and the substrate glutamate. From its position adjacent to the substrate
      glutamate and the cofactor ADP, we propose that this monovalent cation site is
      the substrate ammonium ion binding site. This proposal is supported by enzyme
      kinetics. Our kinetic measurements show that Tl+, Cs+, and NH4+ are competitive
      inhibitors to NH2OH in the gamma-glutamyl transfer reaction. (2) GS is a
      trimetallic enzyme containing two divalent cation sites (n1, n2) and one
      monovalent cation site per subunit. These three closely spaced ions are all at
      the active site: the distance between n1 and n2 is 6 A, between n1 and Tl+ is 4
      A, and between n2 and Tl+ is 7 A. Glu 212 and the substrate glutamate are
      bridging ligands for the n1 ion and Tl+. (3) The presence of a monovalent cation
      in this site may enhance the structural stability of GS, because of its effect of
      balancing the negative charges of the substrate glutamate and its ligands and
      because of strengthening the "side-to-side" intersubunit interaction through the
      cation-protein bonding. (4) The presence of the cofactor ADP increases the Tl+
      binding to GS because ADP binding induces movement of Asp 50' toward this
      monovalent cation site, essentially forming the site. This observation supports a
      two-step mechanism with ordered substrate binding: ATP first binds to GS, then
      Glu binds and attacks ATP to form gamma-glutamyl phosphate and ADP, which
      complete the ammonium binding site. The third substrate, an ammonium ion, then
      binds to GS, and then loses a proton to form the more active species ammonia,
      which attacks the gamma-glutamyl phosphate to yield Gln. (5) Because the products
      (Glu or Gln) of the reactions catalyzed by GS are determined by the molecule
      (water or ammonium) attacking the intermediate gamma-glutamyl phosphate, this
      negatively charged ammonium binding pocket has been designed naturally for high
      affinity of ammonium to GS, permitting glutamine synthesis to proceed in aqueous
      solution.

PMID- 8563632
TI  - Irreversible thermal denaturation of Torpedo californica acetylcholinesterase.
AB  - Thermal denaturation of Torpedo californica acetylcholinesterase, a disulfide
      linked homodimer with 537 amino acids in each subunit, was studied by
      differential scanning calorimetry. It displays a single calorimetric peak that is
      completely irreversible, the shape and temperature maximum depending on the scan
      rate. Thus, thermal denaturation of acetylcholinesterase is an irreversible
      process, under kinetic control, which is described well by the two-state kinetic
      scheme N-->D, with activation energy 131 +/- 8 kcal/mol. Analysis of the kinetics
      of denaturation in the thermal transition temperature range, by monitoring loss
      of enzymic activity, yields activation energy of 121 +/- 20 kcal/mol, similar to
      the value obtained by differential scanning calorimetry. Thermally denatured
      acetylcholinesterase displays spectroscopic characteristics typical of a molten
      globule state, similar to those of partially unfolded enzyme obtained by
      modification with thiol-specific reagents. Evidence is presented that the
      partially unfolded states produced by the two different treatments are
      thermodynamically favored relative to the native state.

PMID- 8563634
TI  - Active site model for gamma-aminobutyrate aminotransferase explains substrate
      specificity and inhibitor reactivities.
AB  - A homology model for the pig isozyme of the pyridoxal phosphate-dependent enzyme
      gamma-aminobutyrate (GABA) aminotransferase has been built based mainly on the
      structure of dialkylglycine decarboxylase and on a multiple sequence alignment of
      28 evolutionarily related enzymes. The proposed active site structure is
      presented and analyzed. Hypothetical structures for external aldimine
      intermediates explain several characteristics of the enzyme. In the GABA external
      aldimine model, the pro-S proton at C4 of GABA, which abstracted in the 1,3
      azaallylic rearrangement interconverting the aldimine and ketimine intermediates,
      is oriented perpendicular to the plane of the pyridoxal phosphate ring. Lys 329
      is in close proximity and is probably the general base catalyst for the proton
      transfer reaction. The carboxylate group of GABA interacts with Arg 192 and Lys
      203, which determine the specificity of the enzyme for monocarboxylic omega-amino
      acids such as GABA. In the proposed structure for the L-glutamate external
      aldimine, the alpha-carboxylate interacts with Arg 445. Glu 265 is proposed to
      interact with this same arginine in the GABA external aldimine, enabling the
      enzyme to act on omega-amino acids in one half-reaction and on alpha-amino acids
      in the other. The reactivities of inhibitors are well explained by the proposed
      active site structure. The R and S isomers of beta-substituted phenyl and p
      chlorophenyl GABA would bind in very different modes due to differential steric
      interactions, with the reactive S isomer leaving the orientation of the GABA
      moiety relatively unperturbed compared to that of the natural substrate. In our
      model, only the reactive S isomer of the mechanism-based inhibitor vinyl-GABA, an
      effective anti-epileptic drug known clinically as Vigabatrin, would orient the
      scissile C4-H bond perpendicular to the coenzyme ring plane and present the
      proton to Lys 329, the proposed general base catalyst of the reaction. The R
      isomer would direct the vinyl group toward Lys 329 and the C4-H bond toward Arg
      445. The active site model presented provides a basis for site-directed
      mutagenesis and drug design experiments.

PMID- 8563635
TI  - Role of the N-terminal region of the skeletal muscle myosin light chain kinase
      target sequence in its interaction with calmodulin.
AB  - The binding of calmodulin (CaM) to four synthetic peptide analogues of the
      skeletal muscle myosin light chain kinase (sk-MLCK) target sequence has been
      studied using 1H-NMR. The 18-residue peptide WFF is anchored to CaM via the
      interaction of the Trp 4 side chain with the C-domain and the Phe 17 side chain
      with the N-domain of the protein. A peptide corresponding to the first 10
      residues (WF10) does not provide the second anchoring residue and is not long
      enough to span both domains of CaM. 1H-NMR spectroscopy indicates that the WF10
      peptide interacts specifically with the C-domain of CaM, and the chemical shifts
      of the bound Trp side chain are very similar in the CaM:WF10 and CaM:WFF
      complexes. Binding of the C-domain of CaM to the strongly basic region around Trp
      4 of this MLCK sequence may be an important step in target recognition.
      Comparison of 1H-NMR spectra of CaM bound to WFF, a Trp 4-->Phe analogue (FFF),
      or a Trp 4-->Phe/Phe 17-->Trp analogue (FFW) suggests that all three peptides
      bind to CaM in the same orientation, i.e., with the peptide side chain in
      position 4 interacting with the C-domain and the side chain in position 17
      interacting with the N-domain. This indicates that a Trp residue in position 4 is
      not an absolute requirement for binding this target sequence and that
      interchanging the Trp 4 and Phe 17 residues does not reverse the orientation of
      the bound peptide, in confirmation of the deduction from previous indirect
      studies using circular dichroism (Findlay WA, Martin SR, Beckingham K, Bayley PM,
      1995, Biochemistry 34:2087-2094). Molecular modeling/energy minimization studies
      indicate that only minor local changes in the protein structure are required to
      accommodate binding of the bulkier Trp 17 side chain of the FFW peptide to the N
      domain of CaM.

PMID- 8563636
TI  - Addition of side chain interactions to modified Lifson-Roig helix-coil theory:
      application to energetics of phenylalanine-methionine interactions.
AB  - We introduce here i, i + 3 and i, i + 4 side chain interactions into the modified
      Lifson-Roig helix-coil theory of Doig et al. (1994, Biochemistry 33:3396-3403).
      The helix/coil equilibrium is a function of initiation, propagation, capping, and
      side chain interaction parameters. If each of these parameters is known, the
      helix content of any isolated peptide can be predicted. The model considers every
      possible conformation of a peptide, is not limited to peptides with only a single
      helical segment, and has physically meaningful parameters. We apply the theory to
      measure the i, i + 4 interaction energies between Phe and Met side chains.
      Peptides with these residues spaced i, i + 4 are significantly more helical than
      controls where they are spaced i, i + 5. Application of the model yields delta G
      for the Phe-Met orientation to be -0.75 kcal.mol-1, whereas that for the Met-Phe
      orientation is -0.54 kcal.mol-1. These orientational preferences can be
      explained, in part, by rotamer preferences for the interacting side chains. We
      place Phe-Met i, i + 4 at the N-terminus, the C-terminus, and in the center of
      the host peptide. The model quantitatively predicts the observed helix contents
      using a single parameter for the side chain-side chain interaction energy. This
      result indicates that the model works well even when the interaction is at
      different locations in the helix.

PMID- 8563637
TI  - Significance of structural changes in proteins: expected errors in refined
      protein structures.
AB  - A quantitative expression key to evaluating significant structural differences or
      induced shifts between any two protein structures is derived. Because
      crystallography leads to reports of a single (or sometimes dual) position for
      each atom, the significance of any structural change based on comparison of two
      structures depends critically on knowing the expected precision of each median
      atomic position reported, and on extracting it for each atom, from the
      information provided in the Protein Data Bank and in the publication. The
      differences between structures of protein molecules that should be identical, and
      that are normally distributed, indicating that they are not affected by crystal
      contacts, were analyzed with respect to many potential indicators of structure
      precision, so as to extract, essentially by "machine learning" principles, a
      generally applicable expression involving the highest correlates. Eighteen
      refined crystal structures from the Protein Data Bank, in which there are
      multiple molecules in the crystallographic asymmetric unit, were selected and
      compared. The thermal B factor, the connectivity of the atom, and the ratio of
      the number of reflections to the number of atoms used in refinement correlate
      best with the magnitude of the positional differences between regions of the
      structures that otherwise would be expected to be the same. These results are
      embodied in a six-parameter equation that can be applied to any
      crystallographically refined structure to estimate the expected uncertainty in
      position of each atom. Structure change in a macromolecule can thus be referenced
      to the expected uncertainty in atomic position as reflected in the variance
      between otherwise identical structures with the observed values of correlated
      parameters.

PMID- 8563638
TI  - Paired natural cysteine mutation mapping: aid to constraining models of protein
      tertiary structure.
AB  - This paper discusses the benefit of mapping paired cysteine mutation patterns as
      a guide to identifying the positions of protein disulfide bonds. This information
      can facilitate the computer modeling of protein tertiary structure. First, a
      simple, paired natural-cysteine-mutation map is presented that identifies the
      positions of putative disulfide bonds in protein families. The method is based on
      the observation that if, during the process of evolution, a disulfide-bonded
      cysteine residue is not conserved, then it is likely that its counterpart will
      also be mutated. For each target protein, protein databases were searched for the
      primary amino acid sequences of all known members of distinct protein families.
      Primary sequence alignment was carried out using PileUp algorithms in the GCG
      package. To search for correlated mutations, we listed only the positions where
      cysteine residues were highly conserved and emphasized the mutated residues. In
      proteins of known three-dimensional structure, a striking pattern of paired
      cysteine mutations correlated with the positions of known disulfide bridges. For
      proteins of unknown architecture, the mutation maps showed several positions
      where disulfide bridging might occur.

PMID- 8563640
TI  - New protein functions in yeast chromosome VIII.
AB  - The analysis of the 269 open reading frames of yeast chromosome VIII by
      computational methods has yielded 24 new significant sequence similarities to
      proteins of known function. The resulting predicted functions include three
      particularly interesting cases of translation-associated proteins: peptidyl-tRNA
      hydrolase, a ribosome recycling factor homologue, and a protein similar to
      cytochrome b translational activator CBS2. The methodological limits of the
      meaningful transfer of functional information between distant homologues are
      discussed.

PMID- 8563639
TI  - How to measure and predict the molar absorption coefficient of a protein.
AB  - The molar absorption coefficient, epsilon, of a protein is usually based on
      concentrations measured by dry weight, nitrogen, or amino acid analysis. The
      studies reported here suggest that the Edelhoch method is the best method for
      measuring epsilon for a protein. (This method is described by Gill and von Hippel
      [1989, Anal Biochem 182:319-326] and is based on data from Edelhoch [1967,
      Biochemistry 6:1948-1954]). The absorbance of a protein at 280 nm depends on the
      content of Trp, Tyr, and cystine (disulfide bonds). The average epsilon values
      for these chromophores in a sample of 18 well-characterized proteins have been
      estimated, and the epsilon values in water, propanol, 6 M guanidine hydrochloride
      (GdnHCl), and 8 M urea have been measured. For Trp, the average epsilon values
      for the proteins are less than the epsilon values measured in any of the
      solvents. For Tyr, the average epsilon values for the proteins are intermediate
      between those measured in 6 M GdnHCl and those measured in propanol. Based on a
      sample of 116 measured epsilon values for 80 proteins, the epsilon at 280 nm of a
      folded protein in water, epsilon (280), can best be predicted with this equation:
      epsilon (280) (M-1 cm-1) = (#Trp)(5,500) + (#Tyr)(1,490) + (#cystine)(125) These
      epsilon (280) values are quite reliable for proteins containing Trp residues, and
      less reliable for proteins that do not. However, the Edelhoch method is
      convenient and accurate, and the best approach is to measure rather than predict
      epsilon.

PMID- 8563641
TI  - Structural similarities in the noncatalytic domains of phenylalanyl-tRNA and
      biotin synthetases.
AB  - Detailed comparison between the structures of the Escherichia coli biotin
      synthetase/repressor protein (BirA) and the recently solved Thermus thermophilus
      phenylalanyl-tRNA synthetase (PheRS) reveals significant similarities outside
      their respective catalytic domains. These comprise a DNA-binding alpha+beta
      domain and an Src-homology 3 (SH3)-like domain that were observed in both
      enzymes. This similarity provides a novel example in which all domains of one
      multidomain protein appear to be constituents of the other multidomain protein
      and supports a concept of a common ancestor for two different synthetase
      families.

PMID- 8563642
TI  - Identification of the catalytic histidine residue participating in the charge
      relay system of carboxypeptidase Y.
AB  - The essential histidine residue of carboxypeptidase Y (CPY) was modified by a
      site-specific reagent, a chloromethylketone derivative of benzyloxycarbonyl-L
      phenylalanine. The single modified histidine residue was converted to N tau
      carboxy-methyl histidine (cmHis) upon performic acid oxidation. A peptide
      containing cmHis was isolated from the tryptic-thermolytic digest. Based on the
      amino acid composition and sequence analysis, the peptide is shown to be Val-Phe
      Asp-Gly-Gly-cmHis-MetO2-Val-Pro, which was derived from CPY cleaved by trypsin at
      Arg 391 and thermolysin at Phe 401, and thus His 397 was modified. This histidine
      residue has been implicated previously by X-ray analysis to participate in the
      charge-relay system of CPY.

PMID- 8563643
TI  - Crystallization and preliminary X-ray diffraction analysis of recombinant
      pentalenene synthase.
AB  - Recombinant pentalenene synthase, a 42.5-kDa sesquiterpene cyclase originally
      isolated from Streptomyces UC5319 and cloned in Escherichia coli, has been
      crystallized in space group P6(3) with unit cell dimensions a = b = 183.5 A and c
      = 56.5 A. Hexagonal prismatic crystals, approximately 0.2 x 0.2 x 0.3 mm,
      diffract to approximately 2.9 A resolution using monochromatic synchrotron
      radiation. From the universal (and achiral) building block, farnesyl
      pyrophosphate, pentalenene synthase catalyzes the formation of four stereocenters
      in the construction of the three fused five-membered rings of pentalenene; this
      novel sesquiterpene is a precursor to the pentalenolactone family of antibiotics.

PMID- 8563644
TI  - Crystallization and preliminary X-ray analysis of fructose 6-phosphate, 2
      kinase:fructose 2,6-bisphosphatase.
AB  - Diffraction-quality crystals of the bifunctional enzyme fructose 6-phosphate, 2
      kinase:fructose 2,6-bisphosphatase from rat testis have been obtained. The
      crystals were grown in the presence of ATP gamma S, fructose 6-phosphate, the
      detergent n-octylglucoside, and the precipitant polyethylene glycol 4000. The
      crystals have the symmetry of the trigonal space group P31/221 with a = b = 83.0
      A and c = 130.6 A. Flash-frozen crystals diffract to beyond 2.2 A, and native
      data have been collected.

PMID- 8563646
TI  - Some early tracer experiments with stable isotopes.

PMID- 8563645
TI  - Crystallization and preliminary X-ray crystallographic analysis of
      phosphoribulokinase from Rhodobacter sphaeroides.
AB  - A recombinant form of Rhodobacter sphaeroides phosphoribulokinase (PRK),
      expressed in Escherichia coli and isolated by affinity chromatography, was
      crystallized by the sitting drop vapor diffusion technique using NH4H2PO4 (pH
      5.6) as the precipitating agent. PRK crystallizes in the cubic space group P432,
      with unit cell parameters a = b = c = 129.55 A. Based on the assumption of one 32
      kDa monomer per asymmetric unit, the Vm value is 2.83 A3/Da. The octameric
      molecular symmetry is consistent with two planar tetramers stacked in a nearly
      eclipsed arrangement. A native data set has been collected to 2.6 A resolution.

PMID- 8563647
TI  - [Possibility of transitioning highly-differentiated Sertoli cells to
      proliferation after exposure to chemical mutagens].

PMID- 8563648
TI  - [Prevention of stress hyperactivation of lipid peroxidation processes with
      modified derivatives of N,N-dibenzylglycine and serotonin].

PMID- 8563649
TI  - [Inhibition of Marburg virus reproduction by glycyrrhizinic acid and its
      derivatives].

PMID- 8563650
TI  - Nonorganic hearing loss and child abuse: beyond the sound booth.
AB  - Nonorganic hearing loss in children can result from many factors. It is possible
      that some children show nonorganic hearing loss because of the stresses of past
      or on-going abuse and neglect. We report three cases of nonorganic hearing loss
      in children with a history of abuse. These cases suggest that among other causes,
      child abuse or neglect is to be ruled out when a child shows false hearing loss.
      Discussions with professionals knowledgeable of a child's home life should be a
      initiated when nonorganic pediatric hearing loss is uncovered.

PMID- 8563651
TI  - Management and outcome: children fitted with hearing aids in Ireland.
AB  - The Republic of Ireland has a total population of 3.5 million people, mainly
      rural or in small towns, a rapidly declining birthrate during 1984 to 1991, and a
      geographically stable children's population. A unified Audiology Service is
      provided by the National Rehabilitation Board for the fitting of hearing aids to
      all children deemed to require them. The current study outlines a database
      analysis of all children fitted with hearing aids for the first time in 1984 or
      1991. Follow-up information on the status (in 1991-1992) of those fitted in 1984
      was obtained, with regard to hearing loss, schooling and changes in aiding. Data
      on severe/profound losses in particular, and the trends in service provision are
      examined. Similar numbers of children were fitted with hearing aids in the two
      years sampled, even though the overall degree of hearing loss amongst this
      population had fallen.

PMID- 8563652
TI  - Changes in acoustic distortion during long term electrical stimulation of the
      guinea pig cochlea: a preliminary study.
AB  - In a preliminary study, acoustic distortion was assessed as a measure of cochlear
      function in both implanted and contralateral ears of electrically stimulated
      guinea pigs. Prestimulation distortion levels in implanted ears were below those
      of unimplanted ears and below those previously reported for guinea pigs. This may
      have been due to the mechanical or irritant effect of the electrode. In both the
      ipsilateral and contralateral ears or stimulated animals, distortion levels were
      depressed during the period of electrical stimulation. In addition, the slope of
      distortion growth as a function of stimulus level was more gradual in stimulated
      ears and contralateral ears of the same animals for f2 = 6 kHz and 9 kHz, but was
      unaffected for f2 = 3 kHz. When the distortion could no longer be recorded in the
      stimulated ear (4 subjects) or contralateral ear (1 subject) the animal was
      killed and histological evaluation carried out in both ears. Histological changes
      were restricted mainly to the efferent terminals in those ears where some
      distortion was still recordable. In one animal where distortion had become
      unmeasurable immediately prior to death, the outer hair cells were severely
      damaged and undergoing lysis. In this preliminary study, intersubject and between
      test variability in distortion for implanted (ipsilateral) ears indicated that
      additional controls are necessary to establish the validity of alterations in
      acoustic distortion to reflect cochlear pathology.

PMID- 8563653
TI  - Coping with noise-induced hearing loss: experiences from the perspective of
      middle-aged male victims.
AB  - The primary aim of this study was to describe coping with noise-induced hearing
      loss (NIHL) from the perspective of middle-aged men. An additional aim was to
      gain a deeper insight in their experiences of suffering from NIHL. Taped
      interviews were conducted with 53 consecutive patients. The interviews focused on
      the subjects' own descriptions of demanding auditory situations and what they
      did, thought and felt in these situations. The verbatim transcribed interview
      protocols were analysed by a method influenced by the tradition of grounded
      theory (Glaser and Strauss, 1967). The first important finding was that the
      coping model, consisting of controlling and avoiding strategies, described by
      Hallberg and Carlsson (1991), was validated by the present data. Second, it was
      shown that avoiding strategies dominated among men with NIHL, although
      situational circumstances, interactional conditions, social closeness and degrees
      of priority, awareness and acceptance sometimes changed the behaviour towards the
      more controlling strategies. Identification of these five factors should be
      regarded as an extension of the original model of coping, a third important
      contribution of this study. The driving force for coping was the hearing impaired
      person's striving to avoid definition as a deviant in social interactions in
      order to maintain a positive (normal) self-image. Health professionals are
      requested to encourage men with NIHL to recognize, confirm and actively seek
      solutions to problems caused by their hearing loss rather than to reinforce their
      denial of hearing difficulties.

PMID- 8563654
TI  - Postural control and vestibulospinal function in patients selected for cochlear
      implantation.
AB  - Postural control, vestibular and eye motor function were evaluated in seven
      postlingually deaf patients before cochlear implantation and were compared with
      21 control subjects. Vibration to the calf muscles or galvanic electrical
      stimulation of the vestibular nerves, perturbed stance and body sway velocity,
      statistical variance of antero-posterior body sway and identification of
      characteristic parameters of postural dynamics were all evaluated. Vibration
      induced body sway was increased among the patients compared with the normal
      subjects and there were differences in characteristic parameters of postural
      dynamics, indicating decreased postural control. Galvanic stimulation induced a
      body sway not significantly different from the control group suggesting that the
      patients selected for cochlear implantation, and with an otherwise reduced
      postural control, are sensitive to electrical stimulation of the vestibular
      nerve. Thus, postlingually deaf subjects who perceive a sensation of sound at
      electrical promontorial stimulation also respond with increased body sway to
      electrical stimulation aimed at the vestibular nerves. This finding may
      contribute an additional hypothesis to the causes of dizziness among cochlear
      implant patients, complementary to the that of wrongly placed electrodes and
      peroperative vestibular lesions.

PMID- 8563655
TI  - An investigation into sound attenuation by earmould tubing.
AB  - A major problem in high-gain post-aural hearing aids is acoustic feedback. One of
      the sources of feedback is the plastic tubing that guides the sound from the
      hearing aid hook to the ear canal. The objectives of this study were to determine
      the effects of increases in tubing wall thickness on the amount of acoustic
      feedback in the hearing aid system and to characterize earmould tubing. Five
      different samples of Tygon tubing were tested, of which four had different wall
      thicknesses; the study also compared Tygon tubing with medical grade PVC tubing.
      Measurement of the wall thickness, taken from scanning electron micrographs,
      showed that the wall thickness differed from the National Association of Earmould
      Laboratories standard by less than 6% and was well within the manufacturer's
      tolerances. Measurement of sound attenuation showed that an increase in the
      tubing wall thickness of 0.330 mm (Tygon 13 Standard to Tygon 13 Double Wall)
      caused an increase in sound attenuation of 2 dB, across the frequency range
      measured (0.5-4 kHz). It was also found that the medical grade PVC had a 5 dB
      greater sound attenuation than the equivalent Tygon tubing. While these
      differences are quite small, they could contribute to a reduction in acoustic
      feedback when used in conjunction with other hearing aid or earmould
      improvements.

PMID- 8563656
TI  - Repair and re-use of hearing instruments.
AB  - Norwegian hearing-impaired persons, since 1 May 1986, have been entitled to free
      hearing instruments (HI), and also to free repair of defective HIs. In order to
      reduce the community's expense, national regulation recommends that HIs not in
      use should be returned to a hearing centre for re-use. To achieve a further
      reduction of expense, the National Health Insurance (NHI) decided that from 1
      January 1989, only persons under 18 years of age could have their HIs repaired
      free of charge. The NHI supposed that some users of HIs would be unwilling to pay
      for repair of defective instruments, and realized that this would lead to an
      increased number of defective HIs remaining among the users. A pilot study
      performed in 1990 supported this assumption. A further consequence of this change
      of regulation was that clients, entitled to free HIs, could not be given used
      instruments with or without reduced guarantee--when they had to pay for repair of
      the instruments themselves. Therefore, the NHI saved expense through user-paid
      repair of HIs, yet on the other hand had increased costs by buying new HIs
      instead of giving some of the clients used instruments. The aim of this
      investigation was to evaluate whether the NHI could pay for the repair of HIs and
      have these costs covered by savings from the re-use of HIs. During 1992, 1993 and
      1994, the cost for repair of the 5150 HIs was 176,560 pounds. During the same
      period, 2105 HIs were re-used, representing a saving of 445,712 pounds. This
      repair/re-use system unburdens the users of HIs of expense, and in turn saves
      money for the community. For approximately 10% of all HIs sent for repair, the
      main problem was not that the instruments were defective.

PMID- 8563657
TI  - Social and cognitive approaches to depression: towards a new synthesis.
AB  - A description of a social-cognitive theory of depression is presented which
      combines the concepts of mental models, personal goals and social roles. An
      analysis is made of how a number of proposals about the onset of depression can
      be summarized as the loss of a valued goal or social role in an individual who
      has few other sources of self-worth. In subsequent sections, limitations of the
      theory are outlined, and the relationship between the present theory and other
      theories of depression is briefly considered.

PMID- 8563658
TI  - ECT and non-memory cognition: a review.
AB  - The literature on the effects of electroconvulsive therapy (ECT) on non-memory
      cognitive functions is reviewed. It is concluded that with early methods of ECT
      administration (sine wave, high dose), these effects are larger than those of
      depression. They are less pronounced, and usually do not exceed the effects of
      depression, when modern methods of ECT administration (brief pulse, moderate or
      low dose) are used. Following ECT, these functions progressively improve. At one
      week to seven months after ECT, performance is better than before ECT, probably
      because of the alleviation of both the effects of depression and of ECT. The time
      course to full recovery of the non-memory effects resembles that of the recovery
      of amnesic effects, although the latter are more pronounced. With bilateral ECT,
      as with right unilateral ECT, there is evidence that right hemisphere effects are
      more pronounced. The results of this review argue that clinicians should take the
      non-memory cognitive effects of ECT into account, and patients should be informed
      of their existence before they sign consent for ECT.

PMID- 8563659
TI  - Reality discrimination, reality monitoring and disposition towards hallucination.
AB  - This investigation tested the hypotheses that individuals disposed towards
      hallucination are deficient in the meta-cognitive skills of reality
      discrimination and reality monitoring, and that there is a strong correlation
      between the measures of these skills. Normal subjects scoring high or low on a
      scale measuring predisposition towards hallucination were tested on an auditory
      signal detection task. High scorers on the scale were found to differ from low
      scorers on a measure of perceptual bias but not on a measure of sensitivity. The
      same groups of subjects were tested on a reality monitoring measure in which they
      were required to monitor two different types of word: words they were required to
      listen to, and words they were required to listen to on some trials and imagine
      on others. On a surprise frequency test it was found that high scorers did not
      differ from low scorers on their ability to accurately count the memories of
      words they had heard. It was also found that both high scorers and low scorers
      overestimated the number of times they had heard words when they had also been
      required to imagine these words on tests; however, high scorers made this error
      to a significantly greater extent. A strong correlation was found between reality
      discrimination and reality monitoring measures for high scorers, but no
      correlation was found for low scorers.

PMID- 8563660
TI  - CAMCOG--a concise neuropsychological test to assist dementia diagnosis: socio
      demographic determinants in an elderly population sample.
AB  - The CAMCOG, which forms part of the CAMDEX interview (Roth et al., 1986, 1988),
      is a brief neuropsychological battery designed to assess the range of cognitive
      functions required for a diagnosis of dementia, and to detect mild degrees of
      cognitive impairment. It was administered to a population sample of 418 elderly
      people (aged 77 and above) in their place of residence. The data show that in
      contrast to the Mini-Mental State Examination, total CAMCOG scores are well
      distributed and there is no ceiling effect. Examination of the association
      between CAMCOG scores and socio-demographic variables (age, sex, education and
      social class) shows that each exerts a significant, and independent, effect upon
      performance. CAMCOG also includes a number of subscale which assess individual
      areas of cognitive function. Of the eight major subscales (orientation, language,
      memory, attention, praxis, calculation, abstract thinking, perception), age was
      significantly related to all but attention; sex with attention, praxis,
      calculation and perception; education with language and abstract thinking; and
      social class with language and perception. In all these analyses, the results
      were adjusted for the effects of the other socio-demographic variables using
      analysis of variance. However, education and social class are highly correlated
      variables and when the association with education is examined without adjusting
      for social class, attention and praxis are also found to be significantly related
      to education. Caution must therefore be taken when using the CAMCOG (or any other
      cognitive test) as a screening test for dementia, using a single, predetermined
      cutpoint. In general, the combination of brevity and breadth of the CAMCOG, along
      with its distributional properties, makes it an attractive neuropsychological
      test for use in the community or the clinic.

PMID- 8563661
TI  - Dependency, self-criticism and social interactions.
AB  - We investigated the social interactions of college students varying in dependency
      and self-criticism. Forty-eight college students used a modified version of the
      Rochester Interaction Record to record quantitative and qualitative features of
      every 10-minute or longer interaction during a seven-day period. Daily measures
      of mood were also collected. Dependency was related to more frequent and more
      intimate interactions, and self-criticism was negatively related to pleasantness
      of social interactions. Although dependency and self-criticism were both
      associated with daily dysphoria, the social interaction findings could not be
      attributed to the effects of mood. The social environments associated with
      dependency and self-criticism may influence the aetiology and course of
      depressive episodes.

PMID- 8563662
TI  - Credibility and outcome of cognitive-behavioural and psychodynamic-interpersonal
      psychotherapy.
AB  - Depressed psychotherapy clients (N = 117) rated the treatment principle
      credibility of cognitive-behavioural (CB) and psychodynamic-interpersonal (PI)
      before they were randomly assigned to receive either eight or 16 sessions of one
      of these treatments, and they rated their expectations of the treatment to which
      they were assigned immediately before (initial credibility) and immediately after
      their first session (emergent credibility). Results indicated that before they
      were assigned to a treatment, clients rated CB treatment principle credibility
      higher than PI treatment principle credibility. After assignment, however,
      clients rated initial credibility similar regardless of whether they were
      assigned to CB or PI therapy, and their ratings of emergent credibility increased
      to a similar degree from immediately before to immediately after the first
      session in both treatments. Clients' endorsement of CB and PI treatment principle
      credibility predicted improvement in PI therapy but not improvement in CB
      therapy. Initial and emergent credibility of clients' assigned treatment
      predicted improvement for clients who received eight sessions of therapy, but not
      for clients who received 16 sessions of therapy. The implications of these
      findings are discussed.

PMID- 8563663
TI  - Recognition memory for words and faces following unilateral temporal lobectomy.
AB  - The study tested the ability of the Warrington Recognition Memory Test (1984) to
      discriminate between patients with left and right temporal lobe lesions. Forty
      seven patients who had undergone unilateral temporal lobectomy (TL) (23 right-
      and 24 left-sided operations) were tested on the two components of the test,
      recognition memory for words (RMW) and recognition memory for faces (RMF). The
      results show that the right TL group were significantly worse than the left TL
      group on RMF. Conversely, the left TL group were significantly worse on the RMW
      test, confirming earlier results relating to material-specific deficits in long
      term memory following TL. The RMF test was relatively sensitive and specific in
      detecting significant impairments associated with right TL, but the RMW proved
      much less sensitive to the effects of left TL. RMW and RMF discrepancy scores
      were found not to discriminate well between the two groups of patients.

PMID- 8563664
TI  - The Italian DAS as a screening instrument for depression in the elderly.
AB  - The accuracy of the 14-item Italian version of the Dysfunctional Attitudes Scale
      (IDAS-14) as a screening tool for depression among elderly people is evaluated
      and compared with the BDI. Results for the IDAS-14 are most satisfactory, since
      high levels of both specificity (0.95) and sensitivity (0.89) may be obtained at
      a given cut-off score (56).

PMID- 8563665
TI  - Childhood onset of spinal cord injury: self-esteem and self-perception.
AB  - The effects of spinal cord injury in childhood upon later psychological
      adjustment were investigated by comparing a group of 86 people injured as
      children with a control group (matched for time since injury and level of injury)
      of people injured as adults. It was hypothesized that adolescence is a crucial
      period in psychological development and that the effect of spinal cord injury on
      body image, self-concept and social relationships during adolescence will have a
      long-term negative effect on psychological well-being. However, on overall
      measures of depression, self-esteem and self-perception, there were no
      significant differences between the experimental and control groups. Furthermore,
      there were no significant differences between paraplegics and tetraplegics,
      between men women, or between those who were involved in a significant intimate
      relationship and those who were not. These findings support previous research
      which has suggested that organic variables, such as age at injury and level of
      injury, are not predictive of long-term psychological adjustment.

PMID- 8563666
TI  - A psychological analysis of menopausal hot flushes.
AB  - Hot flushes and night sweats are one of the main symptoms accompanying the
      menopause, and are a main reason for seeking medical help at this time. This
      study of 61 women (reporting hot flushes once a week or more) investigates
      dimensions of subjective reporting using open questions and rating scales. Two
      separate factors were delineated using a principal component factor analysis -
      frequency (of hot flushes and night sweats) and problem ratings (of distress,
      interference and perception of flushes as problematic) - which had high test
      retest reliability. The frequency ratings correlated highly with prospective
      daily monitoring. Depressed mood, anxiety and low self-esteem, but not frequency,
      discriminated between those who regarded flushes as problematic and those who did
      not. It is suggested that these two subjective measures should be used in
      assessment and in evaluation of hormonal and psychological interventions.

PMID- 8563667
TI  - Measurement of psychological distress in asthma and asthma management programmes.
AB  - The Asthma Bother Profile assesses one of the components of asthma experience:
      asthma distress. An initial questionnaire was constructed from the content of
      earlier asthma quality of life research and modified by comments of 32 asthmatics
      in focus groups. Psychometric analysis of responses of 131 asthmatics to the
      final questionnaire showed that the 15 ?bother items' constitute a unidimensional
      measure of asthma distress with high internal consistency, and the seven
      ?management items' assess the patient's confidence of asthma knowledge,
      perception of the quality of care and confidence in managing asthma attacks.
      Patients who had attended a self-management clinic reported more knowledge of
      asthma, more bother from treatment but not significantly less bother in other
      contexts. Knowledge about when to call the doctor but not knowledge about
      medicine or asthma was correlated with total bother. Self-management programmes
      that encourage problem-focused coping strategies may not reduce asthma distress
      unless distress reduction counselling is included within the education programme.

PMID- 8563668
TI  - Psychological and cardiovascular predictors of anaesthesia induction, operative
      and post-operative complications in minor gynaecological surgery.
AB  - This study aimed to clarify the pre-operative-personality-post-operative-recovery
      association by considering anaesthetic variables. Additionally, the work
      investigated the relationships between psychological and cardiovascular
      functioning and anaesthetic induction difficulties and operative problems. Two
      minor gynaecological procedures were evaluated (dilatation and curettage,
      laparoscopy) which differ greatly in anaesthetic and operative techniques.
      Psychological factors predicted cardiovascular responding immediately prior to
      the induction of anaesthesia, and combinations of cardiovascular and
      psychological variables were associated with anaesthetic induction, operative and
      post-operative problems. Health locus of control and worry concerning the various
      stages of the operation emerged as the most consistent psychological predictors
      of peri-operative outcome in both procedures.

PMID- 8563670
TI  - Gay and lesbian counselling.

PMID- 8563669
TI  - Traumatic spinal cord injury and psychological impact: a cross-sectional analysis
      of coping strategies.
AB  - Many studies have suggested a relationship between coping strategies used to deal
      with stressors and levels of psychological well-being. To explore this further
      the current study examined such relationships in people who have sustained a
      spinal cord injury. Measures of psychological impact and coping strategies were
      taken from those in their sixth week post-injury (N = 41) and those between four
      and seven years post-injury (N = 30). The results were analysed using stepwise
      multiple regression. This provided a number of models containing coping
      strategies that accounted for a certain proportion of the variance in each of the
      psychological impact variables. While the results help to identify specific
      coping strategies associated with better adjustment, they also highlight the need
      to adopt a longitudinal approach in the investigation of psychological responses
      to spinal cord injury.

PMID- 8563671
TI  - The management of hypertension, type A behavior and hostility.

PMID- 8563672
TI  - Effects of training on performance in competitive swimming.
AB  - The relationships between the mean intensity of a training season, training
      volume and frequency, and the variations in performance were studied in a group
      of 18 elite swimmers. Additionally, differences between the swimmers who improved
      their personal record of the previous year during the follow-up training season
      (GIR, n = 8) and those who did not (GNI, n = 10) were investigated. The
      improvement in performance during the follow-up season was significantly
      correlated with the mean intensity of the training season (r = 0.69, p < 0.01),
      but not with training volume or frequency. The performance improvement during the
      follow-up season was negatively related to the initial performance level (r =
      0.90, p < 0.01). The decline in performance during detraining from the previous
      year was less for the GIR than for the GNI (6.21 +/- 2.30% vs. 9.79 +/- 2.18%, p
      < 0.01). The present findings suggest that training intensity is the key factor
      in performance improvement in a group of elite swimmers. Factors such as previous
      detraining and initial performance level could jeopardize success in spite of a
      good adaptation to training.

PMID- 8563673
TI  - Hemodynamics during a machine-aided flexibility protocol.
AB  - Heart rates and systolic and diastolic blood pressures of 15 subjects were
      measured before, during, and after a series of four proprioceptive neuromuscular
      facilitation (PNF) flexibility exercises. The protocol for the study involved the
      use of two new machines, one designed to increase flexibility of the erector
      spinae, the other the hamstrings. Each machine provided constant feedback of
      isometric force, angular displacements, time of contraction, repetitions, and
      other exercise variables. Each bout of exercise involved an isometric contraction
      of the lengthened agonist muscle group (12 sec) followed by a concentric
      contraction of its antagonist in order to place the body part in a more stretched
      position. Hemodynamic measurements were determined at both a perceived maximal
      voluntary isometric contraction (MVIC) and at 50% MVIC. Significant increases in
      hemodynamic factors were observed when exercise measures were compared to pre-
      and postexercise (resting) values. Higher values, though not significantly so,
      were found at MVIC than at 50% MVIC on both machines. All values were well within
      the guidelines of the American College of Sports Medicine.

PMID- 8563674
TI  - Failure of 40 weeks of brisk walking to alter blood lipids in normolipemic women.
AB  - Sedentary, eumenorrheic women (N = 27) 22 to 40 years of age, with high baseline
      levels of plasma high-density lipoprotein cholesterol, were randomly assigned to
      a walking (n = 16) or a control group (n = 11). The training program involved
      treadmill walking 4.8 km (3.0 miles) four times a week for 40 weeks at a mean
      intensity of 72% maximal heart rate. Aerobic power (VO2max) was improved by 22%,
      but no training effect was observed in body composition variables or blood
      lipid/lipoprotein levels. Despite additional increments in exercise intensity
      over the final 20 weeks of training, most of the improvement in VO2max was
      observed over the first 20 weeks of the study. Exercising subjects' baseline
      levels of plasma HDL-C were found to be inversely associated with the change
      (delta) scores in the lipoprotein (r = -0.51, p < or = .05).

PMID- 8563675
TI  - Concentric and eccentric knee extension strength in older and younger men and
      women.
AB  - Decrements in isometric and concentric (Conc) muscular strength with increased
      age are well documented. However, little information is available on the effects
      of aging on eccentric (Ecc) strength, even though Ecc or lengthening muscle
      actions are used in most physical activities. This study examined Conc and Ecc
      peak torques (PT) during knee extension at 90 degrees/sec in healthy older (62 to
      89 yrs) and younger (20 to 29 yrs) men and women. Conc PT decreased more with age
      than did Ecc (p < 0.01), for both men and women. PT values for the older men and
      women as a percentage of those of the younger ones were 58.3 and 46.6% for Conc,
      and 75.1 and 61.7% for Ecc, respectively. These age differences need to be
      considered during isokinetic evaluations of Conc versus Ecc strength. Other
      muscle groups should be investigated, and mechanisms remain to be determined.

PMID- 8563676
TI  - Substrate and hormonal responses during exercise classes at selected stages of
      pregnancy.
AB  - This study examined the substrate and hormonal responses during exercise classes
      for 36 pregnant women at selected stages of pregnancy. Six nonpregnant women
      served as controls. Blood samples were obtained before exercise, at the end of
      aerobic exercise, and 45 min after aerobic exercise. All samples were analyzed
      for substrates (glucose, lactate, FFA) and 7 hormones. Heart rates in the
      pregnant women were approximately 150 bpm, although some were as high as 180 bpm.
      Heart rates in the control group were approximately 130 bpm. Modest increments
      occurred in lactate and FFA during exercise, and decrements in glucose were
      observed in all groups. Insulin concentrations decreased with exercise and
      remained depressed after exercise whereas FFA remained elevated postexercise in
      the pregnant women. Modest transient changes were observed with exercise in the
      other hormones. A severely blunted norepinephrine response to exercise was
      observed in the third-trimester group. In conclusion, uncontrolled non-steady
      state exercise does not disrupt the substrate and endocrine milieu markedly.
      Recovery in hormonal and substrate concentrations appears to occur rapidly after
      exercise. However, decrements in blood glucose do occur for a short time during
      prenatal exercise classes, most notably for women in the third trimester.

PMID- 8563677
TI  - The effect of an aerobic interval training program on intermittent anaerobic
      performance.
AB  - The effects of a 9-week aerobic interval training program on anaerobic
      intermittent performance were investigated. Intermittent work consisted of four
      repeat 30-sec maximal efforts on a cycle ergometer (Wingate test) with 3-min
      recovery intervals. Thirteen men trained 3 days a week on the cycle ergometer,
      completing 3-min work-to-rest intervals and progressing from 5 to 10 reps.
      Relative and absolute values of aerobic power increased significantly for the
      training group (p < .05). No significant change was observed for the control
      group (n = 11). The training group demonstrated significant increases in the four
      anaerobic variables of short-term peak power (SPP), short-term anaerobic capacity
      (SAC), intermediate-term peak power (IPP), and total work (TW), and across the
      four 30-sec maximal repeats for anaerobic performance (T1-T4) (p < .05). Greater
      percentages of increase occurred for IPP and TW, especially during Repeats 3 and
      4. The control group only demonstrated a significant increase in SPP for Repeat
      3. These data suggest that the type of interval training program used in the
      study increased aerobic power and also enhanced performance in repeated high
      intensity, short duration work.

PMID- 8563678
TI  - Delta efficiency of uphill roller skiing with the double pole and diagonal stride
      techniques.
AB  - Delta efficiencies for uphill roller skiing with the double pole (DP) and
      diagonal stride (DS) techniques were determined among 4 female and 4 male cross
      country ski racers in order to examine for differences between techniques and
      between the sexes. Each skier roller-skied on a motorized ski-treadmill at 1.7%
      and 7.1% grades with both techniques at 2 to 4 different speeds. Steady-state
      oxygen uptake values were used to calculate the differences in metabolic
      requirements for roller skiing at the 2 grades (delta E). The differences in
      external work rates between the 2 grades (delta W) were calculated from the work
      rates for overcoming rolling resistance and elevating the transported mass
      against gravity. Delta efficiencies (delta W/ delta E) ranged from 14 to 36%,
      were significantly greater (p < 0.001) for DS than DP, and showed a significant
      (p < 0.01) velocity effect for DS. Delta efficiencies were 27% greater (p < 0.05)
      for the women compared with the men for DP, and significant (p < 0.05)
      correlations were found between efficiency for DP and body mass. This suggests
      that the higher efficiency with DP for female skiers is at least partially due to
      their lower body mass.

PMID- 8563679
TI  - The time course for elevated muscle protein synthesis following heavy resistance
      exercise.
AB  - It has been shown that muscle protein synthetic rate (MPS) is elevated in humans
      by 50% at 4 hrs following a bout of heavy resistance training, and by 109% at 24
      hrs following training. This study further examined the time course for elevated
      muscle protein synthesis by examining its rate at 36 hrs following a training
      session. Six healthy young men performed 12 sets of 6- to 12-RM elbow flexion
      exercises with one arm while the opposite arm served as a control. MPS was
      calculated from the in vivo rate of incorporation of L-[1,2-13C2] leucine into
      biceps brachii of both arms using the primed constant infusion technique over 11
      hrs. At an average time of 36 hrs postexercise, MPS in the exercised arm had
      returned to within 14% of the control arm value, the difference being
      nonsignificant. It is concluded that following a bout of heavy resistance
      training, MPS increases rapidly, is more than double at 24 hrs, and thereafter
      declines rapidly so that at 36 hrs it has almost returned to baseline.

PMID- 8563680
TI  - Unraveling the secrets of Histoplasma capsulatum: a model to study morphogenic
      adaptation during parasite/host interaction.

PMID- 8563681
TI  - [Medical aspects of space flight].

PMID- 8563682
TI  - [Prevention of juvenile diabetes (type 1): reality or fiction?].
AB  - A better knowledge of the pathogenesis of type 1 diabetes (IDDM) may open the
      road to the prevention of the diseases. Primary prevention is meant to identify
      susceptible subjects, either soon after birth or before the immunological
      aggression of beta cells. The practical approach in this respect is very
      difficult because multiple obstacles must be overcome. Secondary prevention
      involves subjects who already show immunological or metabolic alterations, as the
      presence of ICA, antiinsulin antibodies, GAD antibodies and a defect of the first
      phase of insulin secretion. Most authors attach great interest to trials with
      insulin and nicotinamide. Insulin seems to reduce antigen expression when beta
      cells are damaged. Nicotinamide exerts a protection toward diabetes in animals,
      and, as scavanger of free radicals, facilitates beta cell regeneration. Research
      is going on, all over the world, and special multicenter trials are in progress
      both in the USA and Europe.

PMID- 8563683
TI  - [Eulogy of Professor Jules Bordet, Nobel Prize in Medicine and Physiology in
      1919].

PMID- 8563684
TI  - [Eulogy of Professor Corneille Heymans, Nobel Prize in Medicine and Physiology in
      1938].

PMID- 8563685
TI  - [Eulogy of Professor Albert Claude, Nobel Prize in Medicine and Physiology in
      1974].

PMID- 8563686
TI  - [Introduction of Professor George Palade, Nobel Prize in Medicine and Physiology
      in 1974].

PMID- 8563687
TI  - [Introduction of Professor Christian De Duve, Nobel Prize in Medicine and
      Physiology in 1974].

PMID- 8563688
TI  - [Introduction of Professor Ilya Prigogine, Nobel Prize in Chemistry in 1977].

PMID- 8563689
TI  - [Molecular basis of host-parasite relations].

PMID- 8563690
TI  - 1994-1995 influenza season: Canadian laboratory diagnoses and strain
      characterization.

PMID- 8563691
TI  - Dengue fever in Canada.

PMID- 8563692
TI  - Dengue in the Americas.

PMID- 8563693
TI  - Blood pressure variations, hemorheological determinants, and platelet aggregation
      in hypertensive patients with unstable angina.
AB  - Plasma viscosity, fibrinogen, haematocrit and beta-thromboglobulin were assessed
      on venous blood samples taken within 24 hours of admission from 20 consecutive
      male hypertensive patients with unstable angina and 20 male hypertensive patients
      with stable angina, matched for clinical variables. Besides, all patients
      underwent automated indirect blood pressure monitoring for 24 hours, starting
      just after hospitalization. Despite similar average 24-hour, day-time and night
      time systolic and diastolic blood pressure, hypertensive patients with unstable
      angina showed an increased variability of 24-hour (p <0.01) and day-time (p <
      0.05) systolic and disatolic blood pressure, together with higher values of all
      haemorhelogical parameters (plasma viscosity, fibrinogen and haematocrit) (p <
      0.01) and beta-thrombogobulin (p< 0.05), when compared with hypertensive patients
      with stable angina. Moreover, significant correlations between plasma viscosity
      and 24-hour systolic (r = 0.42, p < 0.01) and diastolic (r = 0.39, p < 0.05)
      blood pressure variability were shown in hypertensive patients with unstable
      angina. Besides, in the same patients, the haematocrit was positively correlated
      with 24-hour systolic blood pressure variability (r = 0.37, P < 0.05). Our data
      further support the relevance of rheological determinants, platelet activation
      and haemodynamic factors in the genesis of the high risk condition of unstable
      angina.

PMID- 8563695
TI  - Significance of renal kininases in patients with Cushing's syndrome.
AB  - To further clarify the significance of renal kininases in patients with Cushing's
      syndrome, daily urinary excretions of total kininase, kininase I, Ii and neutral
      endopeptidase 24.11 (NEP) were examined and evaluated for the relations between
      plasma cortisol level and these kininases. Urinary total kininase kininase I, II
      and NEP were significantly higher in patients with Cushing's syndrome than in
      normotensives. There was a significant positive correlation between plasma
      cortisol level and total kininase or NEP, and the same tendency was observed
      between plasma cortisol level and kininase I. After adrenalectomy, urinary
      kininases decreased to normal levels. These findings suggested that: 1) kininase
      I, II and NEP are accelerated in Cushing's syndrome; 2) glucocorticoids may
      regulate renal kininases; and 3) accelerated renal kininases may play some role
      in disorders of the renal water-sodium metabolism and in high blood pressure in
      Cushing's syndrome.

PMID- 8563694
TI  - Dopamine D5 receptor expression is unchanged in peripheral blood lymphocytes in
      essential hypertension.
AB  - The present study was designed to investigate possible changes in the expression
      of lymphocyte dopamine receptor in essential hypertension. The expression of
      dopamine D5 receptor was evaluated by radioligand binding techniques using [3H]
      SCH 23390 as ligand. Plasma catecholamines, aldosterone levels and plasma renin
      activity were also measured. Eleven borderline hypertensive patients, 15 patient
      with the mild essential hypertension, 7 patients with moderate essential
      hypertension and 5 patients with severe essential hypertension were examined.
      Plasma catecholamine levels were assayed by high pressure liquid chromatography
      with electrochemical detection. Dopamine D5 receptor was measured by radioligand
      binding techniques. Plasma aldosterone levels and renin activity were determined
      by radio immunoassay. [3H]-SCH 23390 was specifically bound to human peripheral
      blood lymphocytes. The binding was time-, temperature- and concentration
      dependent with a dissociation constant (Kd) value of 0.59 nM and a maximum
      density of binding sites (Bmax) of 223 pmol/10(6) cells. Dopamine competed with
      [3H]-SCH 23390 binding in the submicromolar range suggesting the labelling of a
      dopamine D5 receptor. No changes in the density of [3H]-SCH 23390 binding sites
      were observed in human peripheral blood lymphocytes between essential
      hypertensive patients and normotensive subjects. Also catecholamines, plasma
      renin activity and aldosterone levels were unchanged. In spite of the
      availability of a sensitive technique for measuring dopamine receptors in human
      peripheral lymphocytes, no change in their expression was noticeable in essential
      hypertension. This suggests that dopamine receptor analysis in essential
      hypertension is not a useful marker for investigating hypertension-dependent
      changes of the peripheral dopaminergic system.

PMID- 8563696
TI  - The mechanisms of the renal effects of neutral endopeptidase inhibitor in rats.
AB  - To further investigate the mechanisms of renal effects of neutral endopeptidase
      24.11 (NEP) inhibition, we employed a specific NEP inhibitor, UK 73967 (UK), with
      or without a specific kinin receptor antagonist, Hoe 140 (Hoe), or nitric oxide
      (NO) synthase inhibitor, N-monomethyl-L-arginine (L-NMMA), in Sprague-Dawley
      rats, and evaluated the urinary NEP, kinins, cGMP and plasma atrial natriuretic
      peptide (ANP). None of the variables changed with vehicle injection. After
      injection of UK, NEP decreased significantly and urinary kinins, cGMP, urine
      volume (UV) and urinary sodium excretion (UNaV) increased significantly. Injected
      Hoe canceled the increase in UV and UNaV induced by UK. Plasma ANP did not show
      any difference between vehicle and UK groups. With a pretreatment of L-NMMA,
      injected UK decreased NEP and increased kinins, while urinary cGMP, UV and UNaV
      did not increase. In conclusion, augmented kinins may play an important role in
      the renal water-sodium metabolism by NEP inhibition, and NO may contribute to the
      kinins' action on this mechanism, while ANP may not contribute to it, at least in
      normotensive rats. Moreover, changes in urinary cGMP do not reflect the changes
      in plasma ANP, but rather, those in NO under this condition.

PMID- 8563697
TI  - The impact of polyamine analogues on the blood pressure of normotensive and
      hypertensive rats.
AB  - The impact of the antineoplastic polyamine analogues N1N14-diethylhomospermine
      (DEHSPM) and N1N11-diethylnorspermine (DENSPM) on the blood pressure and heart
      rate of normotensive and hypertensive rats are described. DEHSPM was administered
      to both normotensive and spontaneously hypertensive rats (SHR), while the DENSPM
      analogue was given only to the normotensive animals. The intravenous
      administration of DEHSPM at doses of 5 or 10 mg/kg resulted in a profound and
      long-lasting drop in the test animals' blood pressure, with no appreciable change
      in their heart rate. This was true for both the normotensive and the hypertensive
      animals. When administered at equivalent molar dosages, DENSPM was one fifth as
      effective as DEHSPM at reducing blood pressure. The impact of NG-nitro-L-arginine
      methyl ester (L-NAME) and L-arginine on the analogues' activity is consistent
      with the involvement of nitric oxide.

PMID- 8563698
TI  - The role of kinins and atrial natriuretic peptide on the renal effects of neutral
      endopeptidase inhibitor in normotensive and hypertensive rats.
AB  - To further elucidate the renal effects of NEP inhibition, we employed NEP
      inhibitor UK 73967 (UK), with or without a kinin receptor antagonist Hoe 140
      (Hoe), in Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats. In
      Sprague-Dawley rats: 1) injected UK significantly decreased NEP, and increased
      kinins, urine volume (UV) and urinary sodium excretion (UNaV), while none of the
      variables changed with vehicle treatment; 2) no difference was found in plasma
      ANP between the vehicle and UK groups; and 3) Hoe canceled the increases of UV
      and UNaV caused by UK. In DOCA-salt rats: 1) infused UK significantly decreased
      NEP, and increased UV and UNaV, while UV and UNaV were slightly decreased, and
      NEP did not change with vehicle treatment; 2) plasma ANP was significantly higher
      in UK group than in the vehicle group; and 3) Hoe could not abolish the increase
      of UV and UNaV induced by UK. These data indicate that the contributions of renal
      kinins and plasma ANP to the diuretic and natriuretic mechanisms of NEP
      inhibition may differ between Sprague-Dawley normotensive rats and DOCA-salt
      hypertensive rats.

PMID- 8563699
TI  - Pharmacology and pharmacokinetics of a novel nonpeptide angiotensin II receptor
      antagonist--DMP 811.
AB  - DMP 811 exhibited high binding affinity for the angiotensin II subtype receptor
      AT1 in rat adrenal tissues with an IC50 of 6 nM, but not for the subtype receptor
      AT2. In the isolated rabbit aorta, DMP 811 inhibited the contractile response to
      angiotensin II selectively and noncompetitively with a KB value of 0.1 nM. In
      conscious renal hypertensive rats, DMP 811 decreased blood pressure with i.v. and
      p.o. ED30s of 0.005 and 0.03 mg/kg, respectively (p.o. ED30 for losartan = 0.59
      mg/kg). In conscious furosemide-treated dogs, DMP 811 given either at 0.3 or 1
      mg/kg p.o. decreased blood pressure. DMP 811 has oral bioavailabilities of 7 and
      29% in rats and dogs, respectively, after a solution dose and 8 and 13%,
      respectively, after a suspension or capsule dosing. Our study indicates that DMP
      811 is a selective and insurmountable AT1 receptor antagonist and is a 20-fold
      more potent orally-active antihypertensive agent than losartan.

PMID- 8563700
TI  - Normalization of insulin resistance in non-obese essential hypertension by
      cilazapril treatment.
AB  - To determine whether ACE inhibitor other than captopril improves insulin
      sensitivity in patients with essential hypertension, we measured insulin
      sensitivity to glucose utilization using SSPG method in 10 lean hypertensive
      subjects before and after chronic cilazapril treatment (1.5 +/- 0.2 mg/day, 15.6
      +/- 2.1 weeks). The results were compared with those obtained in 10 healthy
      control subjects. SSPG obtained by insulin sensitivity test was significantly
      higher in hypertensive subjects, indicating a lower insulin sensitivity than in
      controls. After cilazapril treatment, SSPG reduced significantly to the level
      which was statistically not different from control subjects. Hyperinsulinemia
      diminished after treatment, while no significant change of blood glucose was
      observed during oral glucose tolerance test in hypertensive subjects. Plasma HDL
      cholesterol increased by cilazapril treatment. Cilazapril treatment has
      beneficial effect in the reversal of insulin resistance in patients with
      essential hypertension.

PMID- 8563701
TI  - Effect of renal perfusion pressure on excretion of calcium, magnesium, and
      phosphate in the rat.
AB  - Abnormalities in renal handling of calcium, magnesium, or phosphate have been
      implicated in the development and/or maintenance of human hypertension. We have
      shown recently that renal excretion of these ions is correlated to blood pressure
      in Dahl salt-sensitive as well as salt-resistant rats. The present study was
      designed to determine whether renal perfusion pressure per se could affect
      excretion of these ions. Urinary excretion of calcium, magnesium, and phosphate
      was studied in anaesthetized Sprague-Dawley rats under basal conditions and
      during an intravenous infusion of angiotensin II (ANG II), vasopressin (AVP) or
      phenylephrine (PE). A cuff, placed around the aorta between the two renal
      arteries, allowed maintenance of normal perfusion pressure in the left kidney,
      while that in the right kidney was allowed to rise. Infusion of pressor agents
      raised mean arterial blood pressure to comparable levels (means +/- SE): ANG II
      (n = 7), before = 102 +/- 4, during = 133 +/- 3 mmHg, AVP (n = 8), before = 110
      +/- 7, during = 136 +/- 5 mmHg, PE (n = 6), before = 111 +/- 6, during = 141 +/-
      6 mmHg. Although there was no difference in excretion of calcium, magnesium and
      phosphate between the two kidneys under basal conditions, infusion of ANG II or
      PE induced hypercalciuria, hypermagnesiuria and hyperphosphaturia in the right
      kidney which was exposed to the increased arterial pressure. Such effects did not
      appear in the pressure-controlled left kidney. Infusion of AVP was associated
      with reduced excretion of calcium and magnesium, and increased excretion of
      phosphate, in the normotensive kidney. The response to the similarly increased
      renal perfusion pressure in this group was also reduced for calcium and
      magnesium, and enhanced for phosphate. The results indicate (1) renal excretion
      of calcium, magnesium and phosphate is renal perfusion pressure-dependent; the
      higher the renal perfusion pressure, the greater the excretion of these ions. (2)
      Independently of perfusion pressure, AVP can inhibit phosphate reabsorption and
      stimulate divalent cation reabsorption.

PMID- 8563702
TI  - The pathophysiological role of renal dopamine and kallikrein in
      deoxycorticosterone acetate (DOCA)-salt treated rats.
AB  - To elucidate the pathophysiological role of the renal dopamine (DA) and
      kallikrein-kinin systems in volume dependent hypertension under excess
      mineralocorticoid, the urinary excretions of DA and kallikrein (KAL) were
      investigated in DOCA-salt treated rats (5 week-old Sprague-Dawley rats, DOCA
      100mg pellet, s.c., 1% saline ingestion for 4 weeks, n = 7) for comparison with
      those of control rats (vehicle, 1% saline ingestion for 4 weeks, n = 10). In
      vehicle, systolic blood pressure (SBP), urinary excretion of free DA (UDA) and
      kallikrein (UKAL) did not change through the study. In DOCA treated rats, marked
      natriuresis was observed with sodium load. SBP and UKAL significantly increased
      at the 4th week and at the 2nd week, respectively. UDA increased significantly to
      the peak level at the 1st week, and then decreased gradually. At the 4th week,
      UDA was significantly lower in DOCA-treated rats than that of vehicle rats. A
      significant inverse correlation was found between UDA and SBP, and UKAL
      correlated positively with SBP and urinary excretion of sodium and negatively
      with UDA in DOCA treated rats. These results suggest that the augmentation of
      renal dopaminergic activity which may in part cause sodium escape appears at the
      early stage of DOCA-salt treatment, but this augmentation is subsequently
      blunted; volume and sodium retention may be associated with the blood pressure
      elevation at the late stage of DOCA-salt treatment, and that the augmentation of
      renal kallikrein-kinin system may be a compensatory response to sodium and volume
      retention in DOCA-salt treated rats.

PMID- 8563703
TI  - Use of INAA to study Se, Sb, Zn and Co levels of yeast cells.
AB  - Yeast cells, Saccharomyces cerevisiae, were exposed to Sb(V)(10-5M) and SeO2(10
      4M) or seleno-cystine (CySe)2(5 x 10-5M). Se, Sb, Zn and Co levels of the yeast
      were measured by instrumental neutron activation analysis. The results obtained
      show that in the absence of Se, Sb is taken up by the cells and the highest
      concentration of Sb in the yeast was observed during the initial 2.5 h of
      incubation. Both Se-compounds resulted, in general, in a minute decrease of
      uptake yield of Sb by the cells. This effect can be particularly observed in the
      presence of SeO2. The presence of Sb in the yeast medium slightly increased the
      Se level only after long incubation times. Se uptake by the yeast was higher
      (regardless of Sb dosage) when the yeast was incubated in the medium containing
      (CySe)2 (in comparison with SeO2). The presence of Se-compounds and/or Sb caused
      decrease in the levels of Zn found in the cells. While SeO2 presence resulted in
      minor changes of the Co level of the yeast, the combined presence of Sb and Se
      compounds produced the significant enhancement of Co abundance. The similar
      effect was noted in the yeast incubated in a medium containing only (CySe)2 or
      Sb.

PMID- 8563705
TI  - Ice-based altitude distribution of natural radiation annual exposure rate in the
      Antarctica zone over the latitude range 69 degrees S-77 degrees S using a pair
      filter thermoluminescence method.
AB  - Both ice-based altitude distributions of natural ionizing radiation exposure and
      the quasi-effective energy of natural radiation over Antartica over the latitude
      range 69 degrees S - 77 degrees S during approx. 500 days were measured using
      thermoluminescent dosimeters. The results shows that dependence on altitude above
      sea level of the exposure rate increases by almost three-fold with each increase
      of 2000 m of altitude, thus deviating from the general rule stating that the
      exposure rate should double with each 2000 m. Although the exposure rate shows a
      dependence on altitude, altitude dependence of the quasi-effective energy of
      natural radiation over Antartica is not observed. In the present study it is
      observed that natural radiation occurring over the ice base of Antartica consists
      mainly of cosmic rays.

PMID- 8563704
TI  - Investigation of applicability of alanine and radiochromic detectors to dosimetry
      of proton clinical beams.
AB  - Cancer therapy studies using proton accelerators are underway in several major
      medical centers in the U.S., Russia, Japan and elsewhere. To facilitate dosimetry
      intercomparisons between these laboratories, alanine-based detectors produced at
      the National Institute of Standards and Technology and commercially available
      radiochromic films were studied for their possible use as passive transfer
      dosimeters for clinical proton beams. Evaluation of characteristics of these
      instruments, including the LET dependence of their response of proton energy, was
      carried out at the Institute of Theoretical and Experimental Physics. Results of
      absolute dose measurements were regarded as a preliminary step of dose
      intercomparison between ITEP and NIST. Measurements made in a number of
      experiments showed average agreement between the ITEP and NIST dosimetry
      standards to 2.5%.

PMID- 8563706
TI  - Identification of a microsporidian polar tube protein reactive monoclonal
      antibody.
AB  - The microsporidia are characterized by spores containing a single polar tube that
      coils around the sporoplasm. When triggered by appropriate stimuli, the polar
      tube rapidly discharges out of the spore forming a hollow tube. The sporoplasm
      passes out of the spore through this tube serving as a unique vehicle of
      infection. Due to the unusual functional and solubility properties of the polar
      tube, the proteins comprising it are likely to be members of a protein family
      with a highly conserved amino acid composition among the various microsporidia.
      Polar tube proteins were separated from the majority of other proteins in glass
      bead disrupted spores of Glugea americanus using sequential 1% sodium dodecyl
      sulfate (SDS) and 9M urea extractions. The resultant spore pellet demonstrated
      broken, empty spore coats and numerous polar tubes in straight and twisted
      formations by negative stain transmission electron microscopy. After subsequent
      incubation of the pellet with 2% dithiothreitol (DTT), empty spore coats were
      still observed but the polar tubes were no longer present in the pellet. The DTT
      supernatant demonstrated four major protein bands by SDS-PAGE: 23, 27, 34 and 43
      kDa. Monoclonal antibodies were produced to these proteins using Hunter's
      Titermax adjuvant. Mab 3C8.23.1 which cross-reacted with a 43-kDa antigen by
      immunoblot analysis, demonstrated strong reactivity with the polar tube of G.
      americanus spores by immunogold electron microscopy. This antibody will be useful
      in further characterization of polar tube proteins and may lead to novel
      diagnostic and therapeutic reagents.

PMID- 8563707
TI  - Entamoeba histolytica encodes a highly divergent beta-tubulin.
AB  - The microtubules of the amitochondrial parasite Entamoeba histolytica are
      atypical in certain respects. Consistent with this, we report that E. histolytica
      encodes the most divergent beta-tubulin identified to date, with only 54% to 58%
      identity to beta-tubulins from various species. A similarly divergent beta
      tubulin is encoded by the related Entamoeba invadens; single gene copies appear
      to be present in both organisms. The Entamoeba sequences were compared with a
      database of 101 beta-tubulins, including the highly divergent sequence from
      another amitochondrial protozoan, Trichomonas vaginalis. A total of 81 residues
      were universally conserved, and 76 residues varied only once. Correlations with
      previous studies indicate that microtubule function is altered when most, but not
      all, conserved residues are mutated.

PMID- 8563708
TI  - Characterization of Encephalitozoon (Septata) intestinalis isolates cultured from
      nasal mucosa and bronchoalveolar lavage fluids of two AIDS patients.
AB  - Microsporidia are obligate intracellular protozoan parasites that can cause
      opportunistic infections in AIDS patients. Species from five genera of
      microsporidia are presently known to infect man. One species, Septata
      intestinalis originally was detected in stool specimens of individuals with
      chronic diarrhea and subsequently was found to disseminate to the kidneys, lungs,
      and nasal sinuses. This organism has since been reclassified as Encephalitozoon
      and in this study, we report the culture of Encephalitozoon intestinalis from a
      bronchoalveolar lavage specimen and a nasal mucus aspirate of two AIDS patients
      living in the USA. The bronchoalveolar and nasal microsporidian isolates grew in
      several continuous cell lines including RK-13, MDCK, HT-29, Caco-2, Vero, and
      I047. Transmission electron microscopy of the clinical and cell culture specimens
      revealed that the new isolates appeared to be E. intestinalis based on morphology
      and growth of organisms in septated membrane-bound parasitophorous vacuoles. The
      new E. intestinalis isolates were characterized and compared with the first
      isolated E. intestinalis that was cultured from stool to confirm their identity
      and to determine if there existed any minor differences, as seen in the closely
      related Encephalitozoon cuniculi strains. By the methods of sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis staining for proteins and
      carbohydrates, Western blot immunodetection, and polymerase chain reaction-based
      methods with restriction endonuclease digestion, double-stranded DNA heteroduplex
      mobility shift analysis, and DNA sequencing of the ribosomal DNA intergenic
      spacer region, the new isolates were identical to each other and to the reference
      isolate of E. intestinalis. In addition, with any of these methods, the E.
      intestinalis organisms could be distinguished from the three E. cuniculi strains,
      Encephalitozoon hellem, and Vittaforma corneae, which is important for
      diagnostics, therapeutic strategies, and epidemiology.

PMID- 8563709
TI  - Comparative development of two microsporidian species: Enterocytozoon bieneusi
      and Enterocytozoon salmonis, reported in AIDS patients and salmonid fish,
      respectively.
AB  - Enterocytozoon bieneusi and Enterocytozoon salmonis are reported in HIV-infected
      patients and in salmonid fish, respectively. Both species share the early
      development of the extrusion apparatus of the spores, which is completed prior to
      fission of the sporogonic syncytium into sporoblasts, and the early synthesis of
      polar tube constituents, but they differ in other developmental and sporogenetic
      processes. Enterocytozoon bieneusi develops in direct contact with the cytoplasm
      of epithelial cells whereas E. salmonis occurs only in the nucleus of leucocytes
      and epithelioid cells. Sporogonic nuclei, which are scattered throughout the
      sporont in E. bieneusi, are located in the periphery in E. salmonis. The
      multilamellar structures associated with the nuclear envelopes and the
      endoplasmic reticulum cisternae are specific for E. bieneusi. Additionally, the
      evolution of the polar tube precursors proceeds differently in the two parasites.
      In E. bieneusi, they transform into electron-dense bodies associated with a
      reticulum and polar tubes derive from these structures according to a process
      similar to that reported in other microsporidia. In E. salmonis, polar tube
      precursors fuse directly at their ends and the polar tubes appear to be formed by
      the assemblage of these fused precursors with a material previously synthesized
      in the vicinity of nuclei. In conclusion, both species appear to be less closely
      related than was supposed in earlier descriptions.

PMID- 8563710
TI  - Analyses of 22S dynein binding to Tetrahymena axonemes lacking outer dynein arms.
AB  - Tetrahymena thermophila mutants homozygous for the oad mutation become nonmotile
      when grown at the restrictive temperature of 39 degrees C. Axonemes isolated from
      nonmotile oad mutants (oad 39 degrees C axonemes) lack approximately 90% of their
      outer dynein arms and are deficient in 22S dynein. Here we report that oad 39
      degrees C axonemes contain 40% of the 22S dynein heavy chains that wild-type
      axonemes contain and that oad axonemes do not undergo ATP-induced microtubule
      sliding in vitro. Wild-type 22S dynein will bind to the outer arm position in oad
      axonemes and restore ATP-induced microtubule sliding in those axonemes. Unlike
      wild-type 22S dynein, oad 22S dynein does not bind to the outer arm position in
      oad axonemes. These data indicate that the oad mutation affects some component of
      the outer arm dynein itself rather than the outer arm dynein binding site. These
      data also indicate that oad axonemes can be used to assay outer dynein arm
      function.

PMID- 8563711
TI  - In vitro excystation of Spironucleus muris.
AB  - In vitro excystation of Spironucleus muris cysts, purified by sequential sucrose
      and Percoll gradients from mouse feces, was studied. Three in vitro excystation
      procedures, used for Giardia, were assessed to determine the most useful method.
      Excystation was monitored by light microscopy and subsequently characterized by
      transmission and scanning electron microscopy. Spironucleus muris excysted
      routinely at a level greater than 90% when induced in Hanks' balanced salt
      solution containing sodium bicarbonate at pH 2.0 and transferred to Tyrodes' salt
      solution as an excystation medium. Similarly, high rates of excystation were
      recorded after induction of S. muris cysts in 0.1 M potassium phosphate buffer
      (pH 7.0) with sodium bicarbonate and excystation in trypticase-yeast extract-iron
      medium (TYI medium) or phosphate-buffered saline. A lower rate and percentage of
      excystation were observed after induction of S. muris cysts in an aqueous
      hydrochloric acid solution (pH 2.0) followed by excystation in TYI medium. All
      excystation methods produced extremely active S. muris trophozoites with normal
      morphology. Nonexcysting S. muris cysts have a wall composed of an outer fibrous
      and an inner membranous portion. Following induction, numerous vesicles appeared
      in the peritrophic space. Excystation began by the cyst wall opening at one pole,
      and the anterior part of the trophozoite protruding from the cyst wall. The
      trophozoite emerged progressively from the cyst wall and the empty cyst wall
      appeared to collapse. Excysted trophozoites exhibited normal morphological
      features of S. muris trophozoites isolated from the mouse intestine.

PMID- 8563712
TI  - 2nd Congress of the Hungarian Neuroscience Society. Szeged, 26-28 January 1995.
      Abstracts.

PMID- 8563713
TI  - Areas of dormant glial fibrillary acidic protein (GFAP) immunoreactivity in the
      rat brain as revealed by automated image analysis of serial coronal sections.
AB  - Coronal vibratome sections of the rat brain were immunostained for glial
      fibrillary acidic protein (GFAP) a major cytoskeletal protein typical for
      astrocytes. Using computer-assisted image analysis of whole sections, a
      substantial heterogeneity in regional staining intensities was pointed out. The
      middle layers of the neocortex, the thalamus and caudate-putamen and the tectal
      and tegmental part of the mesencephalon were found to show no detectable
      staining, while peak staining intensities were measured for the pallidum, septal
      triangular nucleus, hippocampus, medial geniculate nucleus and interpeduncular
      nucleus. In some of the negative areas neural lesioning induced the appearance of
      GFAP immunoreaction parallel to an up-regulation of GFAP synthesis. On this basis
      it was assumed that GFAP immunoreactivity is dormant in these astrocytes and
      plastic changes in the neuropil trigger its expression.

PMID- 8563714
TI  - Species-specificity of glial vimentin as revealed by immunocytochemical studies
      with the Vim 3B4 and V9 monoclonal antibodies.
AB  - Two monoclonal antibodies directed against vimentin, Vim 3B4 and V9 could
      distinguish between vimentins originating from certain species, when tested on
      cell lines (Bohn et al, 1992). Our comparative immunohistochemical studies in the
      rat and chicken brain with the same antibodies suggest the coexistence of two
      vimentin forms in the glial cells of both species. One of these forms bearing the
      epitope present in the respective non-glial cell lines is present in astrocytes
      and Bergmann glia independently of the ontogenic state of the animal. The other
      epitope appeared also mutually in both species, albeit its expression was more
      restricted. These patterns suggest that in these two species, the expression of
      the different vimentin forms might be differently regulated.

PMID- 8563715
TI  - Survival of embryonic rat mesencephalic tissue transplanted into cerebral cortex
      in the presence of co-grafted embryonic striatum.
AB  - The transplantation of embryonic dopaminergic tissue is an approach to the
      therapy of parkinsonism. In this study we compared the development of the rat
      embryonic ventral mesencephalon transplanted together or without striatal tissue
      into the cerebral cortex of adult rats. After one month, the survival ratio was
      17 of 44 when striatal tissue was co-grafted, while only 4 of 45 transplants
      survived when the co-graft was omitted. In the mesencephalic graft, the
      appearance of tyrosine hydroxylase-contaning cells was investigated by
      immunohistochemical method. Applying a fluorescent tracer dye, we demonstrated
      the growth of neural fibers from the mesencephalic tissue to the striatal co
      graft. In situ, the embryonic striatal tissue is the natural target area for the
      developing nigrostriatal pathway. The possible role of trophic factors and
      postsynaptic target surfaces provided by the co-graft is discussed as basis of
      the adjuvant effect.

PMID- 8563716
TI  - Neurotransmitter Systems--Modern Technical Approaches. Balatonoszod, Hungary, May
      8-10, 1995. Abstracts.

PMID- 8563717
TI  - Novel aspects of GnRH-induced intracellular signaling and secretion in pituitary
      gonadotrophs.

PMID- 8563718
TI  - Opposing neuroendocrine actions of the natriuretic peptides: C-type and A-type
      natriuretic peptides do not interact with the same hypothalamic cells controlling
      prolactin secretion.
AB  - The two major members of the family of natriuretic peptides (NPs) in brain, A
      type natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) exert
      opposing actions on the neuroendocrine regulation of prolactin (PRL) secretion.
      We have targeted for compromise and destruction cells within the diencephalon
      which bear receptors for ANP (NRP-A receptors), CNP (NRP-B receptors), or both
      peptides (NPR-C receptors) using novel cytotoxin cell targeting methodology in
      order to determine if the neuroendocrine effects of these two peptides are
      exerted on similar cell systems. In animals pretreated with ANP conjugated to the
      cytotoxic A chain of ricin, central administration of a dose of ANP which is
      known to inhibit PRL secretion did not alter PRL levels in plasma; however,
      subsequent administration of CNP elicited the stimulation of PRL secretion. In
      rats pretreated with CNP-ricin A chain conjugate, a treatment we hypothesize
      targets for destruction CNP responsive cells, ANP injection did inhibit PRL
      secretion, while the stimulatory effect of CNP was absent. These results suggest
      that the neuroendocrine effects of these two natriuretic peptides on PRL
      secretion are expressed on different cellular elements of the hypothalamo
      pituitary axis. Furthermore, they reveal that neither peptide acts directly on
      the tuberoinfundibular dopamine system since pretreatment with either cytotoxin
      conjugate failed to alter basal PRL levels. Thus ANP and CNP do not appear to
      express opposing actions on the same cell systems, suggesting the recruitment of
      each peptide individually by differing, unique stimuli for PRL release.

PMID- 8563719
TI  - Cyclosporine effects on in vitro responsiveness of anterior pituitary hormone
      release to dopamine and thyrotropin-releasing hormone in young female rats.
AB  - Endocrine side effects of the immunosuppressive drug cyclosporine (CyA) include
      changes in anterior pituitary hormone secretion. The aim of the present study was
      to examine the effects of CyA on the responsiveness of in situ and ectopic
      anterior pituitary prolactin (PRL), growth hormone (GH) and luteinizing hormone
      (LH) release response to dopamine (DA) and thyrotropin-releasing hormone (TRH)
      treatment in young female rats, and to evaluate the possible PRL participation in
      these effects. Thirty day old rats were rendered hyperprolactinemic by
      transplanting an anterior pituitary gland of a littermate donor, under the kidney
      capsule, and were then injected with CyA or vehicle for 2 or 8 days. Sham
      operated rats were used as controls and treated in the same way. CyA treatment
      prevented the increase in plasma PRL levels which occurred in controls after
      pituitary grafting. In vitro basal PRL release of in situ pituitaries from either
      sham-operated and/or pituitary-grafted animals was decreased by CyA treatment at
      any point studied. Basal in vitro secretion of GH was only decreased in the in
      situ pituitaries from grafted animals after 2 days of CyA therapy. The presence
      of an ectopic pituitary lead to an increase in the in vitro basal LH secretion
      from in situ pituitaries as compared to those from sham-operated rats. Basal LH
      release rates were not changed by CyA treatment, although the LH release in vitro
      did increase in the in situ pituitaries from sham-operated animals treated with
      the drug for 2 days. DA addition to the incubation media decreased the in vitro
      release of PRL, GH and LH from the in situ pituitaries of sham-operated and
      pituitary-grafted animals treated with vehicle. In CyA treated animals, DA
      decreased in vitro PRL release from the in situ pituitaries of animals,
      independently of the presence or absence of an ectopic pituitary. Reductions of
      the in vitro GH and LH release release after DA treatment were higher in the in
      situ pituitaries from grafted animals on day 8 of CyA or vehicle treatment. TRH
      increased the in vitro release of the three hormones with differential effects
      related to the length of the treatment with CyA and/or the presence of an ectopic
      pituitary. In vitro release of PRL and GH by ectopic pituitaries was inhibited by
      previous treatment with CyA and this effect was decreased proportional to the
      duration of the treatment with the drug, while LH secretion was not modified.
      Addition of DA to the incubation media resulted in a marked reduction of in vitro
      PRL and GH release, but only at day 8 of vehicle treatment on GH release did DA
      addition to media further decrease the release of both hormones from ectopic
      pituitaries from animals treated for 2 or 8 days with the drug, whereas LH
      secretion was not modified. TRH addition to the incubation media of ectopic
      pituitaries surprisingly reduced PRL and GH secretion on day 8 of CyA treatment
      or after surgery. The results of these studies suggest that CyA can act directly
      at the hypophyseal level modifying pituitary responsiveness to external stimuli.
      CyA seems to exert its main effects on lactotroph activity while its effects on
      somatotrophs and gonadotrophs are less.

PMID- 8563720
TI  - Increased expression of type 1 angiotensin II receptors in the hypothalamic
      paraventricular nucleus following stress and glucocorticoid administration.
AB  - Double staining in situ hybridization studies have shown that angiotensin II
      (AII) type 1 receptors (AT1) in the hypothalamic paraventricular nucleus (PVN)
      are located primarily in corticotropin releasing hormone (CRH) neurons of the
      parvicellular subdivision. The purpose of these studies was to investigate the
      role of AII regulating the hypothalamic-pituitary adrenal (HPA) axis, by
      correlating AT1 receptor expression levels in the PVN with the known changes in
      activity of the HPA axis under different stress paradigms, and manipulation of
      circulating glucocorticoids. AT1 receptor mRNA was measured by in situ
      hybridization using 35S-labelled cRNA probes and AII binding by autoradiography
      using 125I[Sar1,Ile8]AII in slide mounted hypothalamic sections. AT1 receptor
      mRNA levels and AII binding in the PVN were reduced by about 20% 18 h after
      adrenalectomy remaining at these levels up to 6 days after. This effect was
      prevented by corticosterone administration in the drinking water, or
      dexamethasone injection (100 mg, s.c., daily). Conversely, dexamethasone
      injection in intact rats caused a 20% increase in AT1 receptor mRNA in the PVN.
      AT1 receptor mRNA and binding in the PVN increased 4 h after exposure to stress
      paradigms associated with activation of the HPA axis (immobilization for 1 h, or
      i.p. injection of 1.5 M NaCl), and remained elevated after repeated daily stress
      for 14 days. Unexpectedly, two osmotic stress models associated with inhibition
      of the HPA axis (60 h water deprivation or 12 days of 2% saline intake) also
      resulted in increased AT1 receptor mRNA levels and AII binding in the
      parvicellular PVN. In intact rats, the stimulatory effect of acute stress on AT1
      receptor mRNA in the PVN was significantly enhanced by dexamethasone
      administration (100 micrograms, s.c., 14 h and 1 h prior to stress), while in
      adrenalectomized rats, with or without glucocorticoid replacement, stress reduced
      rather than increased, AT1 receptor mRNA. Dexamethasone, 100 micrograms, injected
      sc within 1 min the beginning of immobilization in adrenalectomized rats,
      increased AT1 receptor mRNA in the PVN to levels significantly higher than those
      after dexamethasone alone, indicating that the stress induced glucocorticoid
      surge is required for the stimulatory effect of stress on AT1 receptor mRNA. The
      data suggest that AT1 receptor expression in the PVN is under dual control during
      stress: stress-activated inhibitory pathways and the stimulatory effect of
      glucocorticoids. The lack of specificity of the changes in AT1 receptor
      expression in the PVN following stressors with opposite effects on ACTH secretion
      (osmotic and physical-psychological stress) does not support a role for AII as a
      major determinant of the response of the HPA axis during stress.

PMID- 8563721
TI  - Nicotine acts directly on pituitary GH3 cells to inhibit prolactin promoter
      activity.
AB  - We have employed the GH3 rat pituitary cell line to investigate whether nicotine
      can regulate prolactin (PRL) gene expression. Nicotine strongly inhibited (45%)
      transient expression of a construct containing the first 187 base-pairs of the
      rat PRL promoter cloned upstream of the chloramphenicol acetyl transferase (CAT)
      gene. This implies that nicotine acts directly on the GH3 cells to inhibit
      transcription directed by the PRL promoter. Expression of a control reporter
      construct containing the CAT gene under the control of the RSV promoter was not
      affected by exposure of the cells to nicotine, demonstrating that the effect of
      nicotine is promoter-specific. The inhibition by nicotine of PRL promoter
      activity was not blocked by hexamethonium, suggesting that this effect of
      nicotine may be mediated by a novel type of nicotine receptor previously
      described in frog pituitary cells. Nicotine was also observed to yield a
      concentration-dependent inhibition of the stimulation by thyrotrophin-releasing
      hormone (TRH) of PRL promoter activity, implying that nicotine can also interfere
      with hormonal regulation of the PRL gene. These results suggest that the reduced
      serum PRL levels that result from smoking may originate in part from decreased
      transcription of the PRL gene resulting from a direct effect of nicotine on
      pituitary PRL-secreting cells.

PMID- 8563722
TI  - Bacterial lipopolysaccharide-induced changes in FOS protein expression in the rat
      brain: correlation with thermoregulatory changes and plasma corticosterone.
AB  - In the present study the regions of the brain showing an increase in the number
      of FOS protein stained cells 180 min following intravenous saline or bacterial
      lipopolysaccharide (LPS) treatment were investigated and correlated with changes
      in body temperature and plasma corticosterone levels. Particular attention was
      given to the possible involvement of the circumventricular organs and regions of
      the brainstem containing central noradrenergic neurones. LPS at doses of 0.35,
      3.5 and 50 micrograms caused highly significant increases in FOS protein
      expression in the organum vasculosum of lamina terminalis, the area postrema and
      the subfornical organ compared with saline controls. Marked increases in
      bacterial lipopolysaccharide-induced FOS protein expression were observed in the
      ventrolateral medulla, the nucleus of the solitary tract and the locus coeruleus
      which contain the A1, A2 and A6 noradrenergic neurones respectively. The changes
      in body temperature induced by LPS were found to be dependent upon the dose of
      LPS administered; the lowest dose employed (0.35 micrograms) induced an immediate
      and sustained fever, 3.5 micrograms LPS caused a biphasic response consisting of
      a hypothermic response followed by a febrile response, whereas 50 micrograms LPS
      induced a hypothermic response which then normalised by 160 min post-injection.
      Intravenous saline injection had no significant effect on body temperature. The
      occurance of LPS-induced hypothermia was coincident with increased FOS expression
      in the bed nucleus of stria terminalis, which houses vasopressinergic neurones
      involved in antipyresis, whereas in animals showing an LPS-induced febrile
      response there was no significant difference in the number of FOS stained cells
      in the bed nucleus of stria terminalis compared with saline treated animals. LPS
      also caused marked increases in FOS protein expression in the parvocellular
      regions of the paraventricular nucleus (pPVN) of the hypothalamus, the central
      nucleus of the amygdala and the ventral septal area. Plasma corticosterone was
      unaffected by the lowest dose of LPS (0.35 micrograms), however the higher doses
      employed (3.5 and 50 micrograms) caused significant increases in plasma
      corticosterone which correlated with the increases in the number of FOS stained
      cells in the pPVN. The results of the present study suggest that, in addition to
      the organum vasculosum of lamina terminalis, the area postrema and subfornical
      organ may be important in the responses to antigenic challenge that are mediated
      by the central nervous system. They also add support to the possible involvement
      of the bed nucleus of stria terminalis in LPS-induced hypothermia and of the
      involvement of the of the major noradrenergic cell groups (A1, A2 & A6) and a
      number of hypothalamic and extrahypothalamic forebrain regions in the interaction
      of immune and central nervous systems.

PMID- 8563723
TI  - Central glucopenia induced by 2-deoxy-D-glucose stimulates somatostatin secretion
      in the rat.
AB  - The mechanisms involved in 2-deoxy-D-glucose (2-DG)-induced growth hormone (GH)
      suppression in the rat were examined. Conscious male rats were given 2-DG by
      intracerebroventricular (icv) injection and the pulsatile GH secretion was
      monitored for 6 h. The single icv injection of 2-DG (8 mg/rat) eliminated
      pulsatile GH secretion in conscious rats. Pretreatment with somatostatin (SS)
      antiserum completely restored the suppressed GH secretion in the 2-DG treated
      rats. Hypothalamic GH-releasing hormone (GRH) and SS mRNA levels were not altered
      by single and multiple icv injections of 2-DG. These findings suggest that 2-DG
      induced GH suppression is primarily due to hypersecretion of SS without a
      significant change at the transcription level in the rat.

PMID- 8563724
TI  - Biosynthesis and processing of the N-terminal part of proopiomelanocortin in
      Xenopus laevis: characterization of gamma-MSH peptides.
AB  - The aim of this study was to determine the terminal products of processing of the
      N-terminal part of proopiomelanocortin (POMC) in pituitary melanotrope cells of
      Xenopus laevis. Biosynthetic in vitro labelling studies showed that POMC is
      rapidly processed to form N-terminal peptides with an estimated molecular mass of
      18 kDa, 9 kDa and 4 kDa. All peptides were released into the medium, indicating
      that they are processing end products. An antiserum was raised against the
      synthetic N-terminal eight amino acids of the putative Xenopus gamma-MSH which is
      present in the N-terminal part of POMC. With immunocytochemistry we demonstrated
      that gamma-MSH-immunoreactive material in the pituitary gland is restricted to
      the pars intermedia. A radioimmunoassay in combination with reversed-phase HPLC
      revealed the presence of at least two gamma-MSH-like peptides. Complete
      purification followed by electrospray ionization mass spectrometry and amino acid
      sequence determination showed that these peptides are gamma 1-MSH and
      glycosylated gamma 3-MSH. The amounts of these gamma-MSH peptides were low
      compared to the other POMC-derived peptides, alpha-MSH and beta-endorphin. Only
      10% of POMC is processed into gamma-MSH peptides and the 4 kDa peptide, leaving
      the 18 kDa and 9 kDa peptides as the major end products.

PMID- 8563725
TI  - Infections, idiotypes and SLE.

PMID- 8563726
TI  - Response criteria for clinical trials in systemic lupus erythematosus.
AB  - For clinical trials of mild to moderately active systemic lupus erythematosus, a
      criteria for a responder is proposed. An a priori definition has a variety of
      advantages including the ability to compare trials with one another, expand the
      potential number of eligible subjects; increase sensitivity and reduce sample
      size requirements; exploit innovative; expedient clinical trial designs; and also
      quantitate a flare, as well. The availability of quantitative disease activity
      measures permits the development of a responder index.

PMID- 8563727
TI  - Enhancement of renal disease in BXSB lupus prone mice after prior exposure to
      bacterial lipopolysaccharide.
AB  - The mechanism, or mechanisms, responsible for enhancement of renal disease after
      episodes of infection are poorly understood. We used the BXSB mouse as a lupus
      model of autoimmune disease and we used bacterial lipopolysaccharide (LPS) as a
      surrogate infectious agent to gain some insight into the mechanism by which
      infections promote enhancement of autoimmune disease to chronicity. BXSB mice
      were exposed to LPS for 5 weeks, LPS was withdrawn and various tests and
      measurements were performed 6 weeks thereafter. Matched BXSB mice exposed to
      vehicle injections for 5 weeks served as controls. We verified that previous
      exposure to LPS enhances polyclonal B cell activation, impairs carrier function
      of blood cells for immune complexes, increases deposition of immune complexes in
      the microcirculation and promotes glomerular inflammation and sclerosis. These
      changes occurred at 6 weeks after withdrawal of LPS in the presence of unimpaired
      function of mononuclear phagocytes. Some of the effects of LPS are reversible,
      others are partially so and others are irreversible. Altered immune functions
      elicited by prior exposure to LPS can result in enhanced involvement of various
      renal compartments and can result in renal insufficiency.

PMID- 8563728
TI  - Prolactin and systemic lupus erythematosus: prolactin secretion by SLE
      lymphocytes and proliferative (autocrine) activity.
AB  - Accumulated evidence suggests that prolactin (PRL) is an important
      immunoregulator and might have a role in the pathogenesis of systemic lupus
      erythematosus (SLE). Moreover, a PRL-like molecule is secreted by normal human
      lymphocytes and acts as an autocrine growth factor for lymphoproliferation. The
      objective of this study was to explore the PRL-like peptide production by
      peripheral blood mononuclear cells (PBMC) from patients with SLE. We investigated
      the PRL secretion by PBMC from six female SLE patients and nine normal subjects
      (5 women and 4 men). Ficoll-Hypaque isolated PBMC (1 x 10(6) cells/ml) were
      cultured with and without maximal stimulatory doses of PHA (1 mg/ml) or PWM
      (1/200). At 72 h of culture supernatants were harvested and used to determine PRL
      immunoreactivity by a radioimmunoassay (NIDDK-reagents). Cell extracts and
      concentrated supernatants were prepared to determine PRL by Western blot analysis
      (NIDDK-reagents). SLE non-stimulated PBMC secreted significantly higher levels of
      PRL than normal non-stimulated PBMC (8.09 +/- 4.15 ng/ml vs. 3.48 +/- 2.36 ng/ml,
      P = 0.02 by Mann-Whitney test). High levels of PRL were secreted by SLE-PHA
      stimulated PBMC (6.88 +/- 4.53 ng/ml) and SLE-PWM stimulated PBMC (16.57 +/-
      16.39 ng/ml) compared with normal-PHA stimulated PBMC (5.83 +/- 5.27 ng/ml) and
      normal-PWM stimulated PBMC (8.54 +/- 5.49 ng/ml), respectively, but the
      differences were not significant. The maximal production of PRL was found in PWM
      stimulated lymphocytes in both groups. Cells extracts prepared from SLE non
      stimulated and stimulated PBMC contained a 11 KDa PRL immunoreactive material.
      Concentrated supernatants from SLE non-stimulated and stimulated PBMC contained
      both a 11 KDa and a 24-27 KDa PRL immunoreactive material. Our data indicate that
      PBMC from patients with SLE have an increased production of PRL-like
      immunoreactive material. This PRL is released in vitro as two different molecular
      weight forms, and appears to be derived from B rather than T lymphocytes.

PMID- 8563729
TI  - Synovial fluid cells in systemic lupus erythematosus: light and electron
      microscopic studies.
AB  - Joint fluid findings in systemic lupus erythematosus (SLE) have been described in
      only a few series and systematic electron microscopic study of the synovial fluid
      (SF) cells has not been reported. We describe the evaluation of 17 SF in patients
      with SLE with routine analysis and electron microscopy. Joint effusions had a
      wider range of leukocyte counts than often appreciated, with counts varying from
      875 to 39,250 cells per mm3. LE inclusions were seen in eight fluids and have
      been shown to contain chromatin-like filaments by electron microscopy. There was
      little associated electron dense immunoglobulin-like material. Tubuloreticular
      structures (TRS) found in seven SF were mostly in mononuclear cells including
      some LE cells. The known association of TRS with alpha interferon and viral
      infections may have important implications for pathogenesis.

PMID- 8563730
TI  - Longitudinal measurement of anticardiolipin antibodies during normal pregnancy: a
      prospective study.
AB  - We have previously shown that elevation of anticardiolipin antibodies (aCL) at
      the first prenatal visit is associated with increased fetal loss in normal
      pregnancy. The variation in aCL levels during normal pregnancy has not been
      established. To examine this question we measured IgG, IgM and IgA aCL levels
      five times during pregnancy at weeks 5-15, 16-25, 26-35, 36-37 and at delivery.
      Data were analyzed to determine: (a) the within and between subject variability
      of aCL during pregnancy; (2) the temporal trend of aCL; and (3) the relation of
      serial measures of aCL with maternal complications of pregnancy. We divided our
      cohort of 354 subjects into two groups. Group A included those subjects with
      consistently normal levels of aCL and group B those subjects with at least one
      elevated level of aCL. In group A the within subject variability was relatively
      low (28-34%). In group B we found wide fluctuations in aCL levels and a within
      subject variability of 88-91%. Subjects in group B had no increase in maternal
      complications of pregnancy. The present data suggest that aCL may fluctuate
      significantly during normal pregnancy and there is little clinical value in
      measuring aCL on a serial basis during pregnancy.

PMID- 8563731
TI  - Clinical evaluation of various selected ELISA kits for the detection of anti-DNA
      antibodies.
AB  - Fifty four coded sera, 38 from eight patients with systemic lupus erythematosus
      (SLE), four from one patient with systemic vasculitis, one from one patient with
      polyarthritis and 11 normal controls were tested for anti-dsDNA antibodies using
      seven commercial enzyme linked immunosorbent assays (ELISA) and the
      radioimmunoassay method (RIA) routinely used in our unit. Sensitivity,
      specificity and predictive values were tested for both SLE diagnosis and disease
      activity. Using anti-dsDNA antibodies as a diagnostic test for SLE there were
      differences in sensitivity (from 66% to 95%), specificity (from 75% to 100%),
      predictive positive values (from 89% to 100%) and predictive negative values
      (from 50% to 87%) among ELISA kits. The RIA method was either more specific or
      equal to ELISA kits. Using 'equivocal' values as positive values an increase in
      sensitivity was observed but at the expense of specificity. Similar differences
      and trends were observed when the results were used as a measure for disease
      activity. This suggests that there are differences in sensitivity, specificity
      and predictive values among ELISA kits both in the diagnosis of SLE as well as in
      the determination of disease activity.

PMID- 8563732
TI  - Analysis of three new idiotypes on human monoclonal autoantibodies.
AB  - We have identified and characterised three new idiotypes on human IgM McAbs
      generated from the splenocytes of a SLE patient with active disease. RT-6, which
      binds H1 and Sm/RNP, expresses essentially a private Id. Its expression is
      limited to a small number of human McAbs and the sera from patients with
      infectious diseases. In contrast RT-72Id and RT-84Id, expressed on McAbs which
      are polyreactive for two or more antigens, have a public distribution. RT-72Id
      and RT-84Id are found on McAbs from murine and human adult, and foetal tissues.
      In sera, significant numbers of SLE, RA and patients with other autoimmune
      diseases are positive for both Ids. RT-84Id is also elevated in SLE relatives and
      spouses, and in patients with Klebsiella infection. No correlation with disease
      activity, IgM or IgG levels was observed with either Id. However, RT-72Id was
      significantly associated with anti-ssDNA antibodies and RhF. RT-6Id and RT-72Id
      are located on the framework regions of the mu heavy chain, whereas RT-84Id is
      present on the kappa light chain, within the binding site. The McAbs are encoded
      by mainly germline genes: heavy chains of RT-6, RT-72 and RT-84 are encoded by
      the genes VH26, VH4.22 and VH4.21, respectively, and the light chain sequences of
      RT-6 and RT-72 are derived from DPL11 and HK102. Immunofluorescent staining
      revealed the presence of RT-72Id and RT-84Id positive immunoglobulin deposits in
      18% and 45%, respectively, of the lupus renal sections compared with none in the
      disease control group, suggesting that these Ids may contribute to the pathology
      of the disease.

PMID- 8563733
TI  - Lack of association between the MHC linked OTF3 gene and systemic lupus
      erythematosus.
AB  - The objective of this study was to investigate whether an octamer transcription
      factor gene (OTF3) located within the MHC region of chromosome 6 is involved in
      determining susceptibility to systemic lupus erythematosus (SLE) in a Spanish
      population. An OTF3 HindIII polymorphism was characterized by restriction
      fragment length polymorphism analysis of polymerase chain reaction amplified
      genomic DNA in 69 patients with SLE and 60 controls. No differences in the OTF3
      allelic or genotypic distribution between healthy controls and patients with SLE
      were found. In the group of patients with diffuse proliferative
      glomerulonephritis, where we have previously detected the strongest MHC
      association, we did not observe OTF3 linkage either. In conclusion, the OTF3 gene
      does not appear to be associated with SLE in the Spanish population. This might
      be due to the distance of the gene from the HLA class II-III region where more
      relevant autoimmune-related genes are located.

PMID- 8563734
TI  - Serum interleukin 10 titers in systemic lupus erythematosus reflect disease
      activity.
AB  - We investigated whether serum titers of interleukin 10 (IL-10), a cytokine known
      to shift lymphocyte responses towards humoral immunity, reflect disease activity
      in systemic lupus erythematosus (SLE). Sera from 72 SLE patients, 25 RA patients
      and 30 healthy controls were tested for IL-10 by ELISA. Low titers of IL-10 were
      detected in the serum of 37.5% of SLE patients and in 24% of RA patients but in
      only 3% of healthy controls. Interestingly, serum IL-10 titers in SLE patients
      were positively correlated with the SLE Disease Activity Index (SLEDAI) and with
      anti-DNA antibody titers, but negatively with complement fraction C3 levels.
      These results indicate that serum IL-10 values reflect SLE disease activity and
      suggest that overexpression of IL-10 might play a pathogenic role in severe lupus
      disease.

PMID- 8563735
TI  - Cytomegalovirus infection induces expression of 60 KD/Ro antigen on human
      keratinocytes.
AB  - To investigate the effect of human cytomegalovirus (CMV) infection on the
      expression of Ro autoantigen in human keratinocytes, the binding of anti-Ro
      peptide antibodies (anti-60 KD/Ro, anti-52 KD/Ro and anti-calreticulin) to
      cultured human keratinocytes was detected by fixed cell enzyme-linked immunoassay
      (ELISA), immunofluorescence, flow cytometry (FACS) analysis and immunoblotting.
      There was a significant increase in the binding of anti-60 KD/Ro antibody but not
      anti-52 KD/Ro or anti-calreticulin antibody to the surface of cultured
      keratinocytes at 24 h after CMV infection compared with uninfected cells, by
      ELISA and immunofluorescence. Surface binding of anti-60 KD/Ro was found in 71.2%
      (+/- 5.5%) of CMV-infected cells compared with 26.2% (+/- 4.1%) of untreated
      cells (P < 0.05) by FACS analysis. Similar observations were made with a human
      serum which contained anti-60 KD/Ro antibodies. Immunoblotting was used to
      analyse total cellular 60 KD/Ro antigen expression in keratinocytes infected with
      CMV or without infection. No increase in the intensity of the 60 KD band was
      found in extracts of the CMV-infected cells, suggesting that the 60 KD/Ro antigen
      is redistributed from the cytoplasm to the cell surface after viral infection.
      The effects of CMV infection on cell cultures were compared with those of
      ultraviolet B (UVB) irradiation. The 60 KD/Ro, 52 KD/Ro and calreticulin were all
      induced on the UVB-irradiated cell surface but not significant synergistic effect
      of UVB and CMV was found. This study provides evidence that CMV infection induced
      60 KD/Ro antigen expression on the surface of human keratinocytes, suggesting
      that CMV may play a role in development of skin lesions in systemic lupus
      erythematosus (SLE).

PMID- 8563736
TI  - Erythrocyte aplasia and systemic lupus erythematosus.
AB  - Pure erythrocyte aplasia is a recognised feature of systemic lupus erythematosus
      (SLE); here we report two cases, one predating the onset of SLE, the other
      following a long period of disease quiescence. One case demonstrates the typical
      features of this disorder and was successfully treated with prednisolone. The
      second case is unusual in being resistant to immunosuppressive treatment. Bone
      marrow culture from the second patient revealed an inhibition of BFU-E colony
      formation in the presence of the patient's serum, indicating that a serum
      inhibitor of haemopoiesis was present. Furthermore, following T cell depletion of
      this patient's marrow, there was an increase in BFU-E, CFU-G and CFU-GM colony
      growth implicating, in addition, a possible T cell-mediated inhibition of marrow
      haemopoiesis. This is a novel observation and may explain the resistance shown by
      this patient to standard treatment.

PMID- 8563737
TI  - Cerebellar atrophy in systemic lupus erythematosus.
AB  - Central nervous system involvement in systemic lupus erythematosus (SLE) is
      common; this is especially so in patients with positive antiphospholipid
      antibody. However, cerebellar involvement is very unusual. In our institution, we
      have seen 150 cases of SLE over the last 10 years; however, this is the only
      patient who has cerebellar involvement due to SLE. The patient had no other
      neurological deficit, and no other cause apart from her SLE to explain her
      cerebellar ataxia. Her antiphospholipid antibody was negative. The patient showed
      some improvement on high-dose steroids and azathioprin.

PMID- 8563738
TI  - When does amyloidosis complicate systemic lupus erythematosus?
AB  - Secondary amyloidosis is a well recognised complication of rheumatic diseases,
      but the association with systemic lupus erythematosus is very unusual. We report
      the case of a patient with systemic lupus erythematosus who developed proteinuria
      due to renal amyloidosis. We also review the cases previously reported and the
      hypothesis on the pathogenic mechanisms.

PMID- 8563739
TI  - Ovaries in systemic lupus erythematosus.

PMID- 8563740
TI  - Indian incense and sensibility.

PMID- 8563741
TI  - The malevolence of matchmaking.

PMID- 8563742
TI  - Ain't misbehavin'--it's genetic!

PMID- 8563743
TI  - A map to the future.

PMID- 8563744
TI  - John Jacob Wasmuth (1946-1995).

PMID- 8563745
TI  - Breaking laws and obeying rules.

PMID- 8563746
TI  - Glucagon receptor gene mutation in essential hypertension.

PMID- 8563747
TI  - CNTF and endogenous psychoses?

PMID- 8563748
TI  - What's in a face?
AB  - Genetic syndromes causing human facial abnormalities have been extensively
      studied from the clinical point of view. In these syndromes, distinctive facial
      features are frequently associated with specific defects of other organ systems,
      and the genes responsible must all play a significant part in normal development.
      In this paper genes causing craniofacial abnormalities, that have either been
      mapped or isolated, are reviewed.

PMID- 8563749
TI  - Positional cloning of a gene involved in the pathogenesis of Treacher Collins
      syndrome. The Treacher Collins Syndrome Collaborative Group.
AB  - Treacher Collins syndrome is an autosomal dominant disorder of craniofacial
      development, which has been localized to chromosome 5q32-33.1. In the present
      study, the isolation of new polymorphic markers has allowed the identification of
      overlapping recombination events in two affected individuals. Extension of the
      transcription map of the critical region proximally has resulted in the isolation
      of a new gene (which has been named Treacle) of unknown function. The
      identification of different mutations in five unrelated families, all of which
      would result in premature termination of the predicted protein, indicates that
      the Treacher Collins syndrome gene has been positionally cloned.

PMID- 8563750
TI  - Nf1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating
      factor hypersensitivity and chronic myeloid leukaemia.
AB  - The Ras signal transduction pathway is often deregulated in human myeloid
      leukaemia. For example, activating point mutations in RAS genes are found in some
      patients with juvenile chronic myelogenous leukaemia (JCML), while other patients
      with JCML show loss of the neurofibromatosis type 1 (NF1) gene, a Ras GTPase
      activating protein. By generating mice whose haematopoietic system is
      reconsituted with Nf1 deficient haematopoietic stem cells we show that Nf1 gene
      loss, by itself, is sufficient to produce the myeloproliferative symptoms
      associated with human JCML. We also provide evidence to indicate that Nf1 gene
      loss induces myeloproliferative disease through a Ras-mediated hypersensitivity
      to granulocyte/macrophage-colony stimulating factor (GM-CSF). Finally, we
      describe a genetic screen for identifying genes that cooperate with Nf1 gene loss
      during progression to acute myeloid leukaemia.

PMID- 8563751
TI  - Loss of NF1 results in activation of the Ras signaling pathway and leads to
      aberrant growth in haematopoietic cells.
AB  - Individuals with neurofibromatosis type 1 (NF1) are predisposed to certain
      cancers including juvenile chronic myelogenous leukaemia (JCML). The NF1 tumour
      suppressor gene encodes a protein (neurofibromin) that accelerates GTP hydrolysis
      on Ras proteins. Here we show that primary leukaemic cells from children with NF1
      show a selective decrease in NF1-like GTPase activating protein (GAP) activity
      for Ras but retain normal cellular GAP activity. Leukaemic cells also show an
      elevated percentage of Ras in the GTP-bound conformation. JCML cells are
      hypersensitive to granulocyte-macrophage colony stimulating factor (GM-CSF), and
      we observed a similar pattern of aberrant growth in haematopoietic cells from Nf1
      /- mouse embryos. These data define a specific role for neurofibromin in
      negatively regulating GM-CSF signaling through Ras in haematopoietic cells and
      they suggest that hypersensitivity to GM-CSF may be a primary event in the
      development of JCML.

PMID- 8563752
TI  - Cooperative activation of Hoxa and Pbx1-related genes in murine myeloid
      leukaemias.
AB  - Retroviruses induce myeloid leukaemia in BXH-2 mice by the insertional mutation
      of cellular proto-oncogenes or tumour suppressor genes. Disease genes can thus be
      identified by proviral tagging through the identification of common viral
      integration sites in BXH-2 leukaemia. Here, we describe a new approach for
      proviral tagging that greatly facilitates the identification of BXH-2 leukaemia
      genes. Using this approach, we identify three genes whose expression is activated
      by proviral integration in BXH-2 leukaemias; Hoxa7, Hoxa9, and a Pbx1-related
      homeobox gene, Meis1. Proviral activation of Hoxa7 or Hoxa9 is strongly
      correlated with proviral activation of Meis1 implying that Hoxa7 and Hoxa9
      cooperate with Meis1 in leukaemia formation. These studies provide the first
      genetic evidence that Pbx1-related genes cooperate with Hox genes in leukaemia
      formation and identify a number of new murine myeloid leukaemia genes.

PMID- 8563753
TI  - Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation
      t(7;11)(p15;p15) in human myeloid leukaemia.
AB  - Expression of Hoxa7 and Hoxa9 is activated by proviral integration in BXH2 murine
      myeloid leukaemias. This result, combined with the mapping of the HOXA locus to
      human chromosome 7p15, suggested that one of the HOXA genes might be involved in
      the t(7;11)(p15;p15) translocation found in some human myeloid leukaemia
      patients. Here we show that in three patients with t(7;11), the chromosome
      rearrangement creates a genomic fusion between the HOXA9 gene and the nucleoporin
      gene NUP98 on chromosome 11p15. The translocation produces an invariant chimaeric
      NUP98/HOXA9 transcript containing the amino terminal half of NUP98 fused in frame
      to HOXA9. These studies identify HOXA9 as an important human myeloid leukaemia
      gene and suggest an important role for nucleoporins in human myeloid leukaemia
      given that a second nucleoporin, NUP214, has also been implicated in human
      myeloid leukaemia.

PMID- 8563754
TI  - The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for
      nucleoporin NUP98 and class I homeoprotein HOXA9.
AB  - The t(7;11)(p15;p15) translocation is a recurrent chromosomal abnormality
      associated primarily with acute myeloid leukaemia (FAB M2 and M4). We present
      here the molecular definition of this translocation. On chromosome 7 positional
      cloning revealed the consistent rearrangement of the HOXA9 gene, which encodes a
      class I homeodomain protein potentially involved in myeloid differentiation. On
      chromosome 11 the translocation targets the human homologue of NUP98, a member of
      the GLFG nucleoporin family. Chimaeric messages spliced over the breakpoint fuse
      the GLFG repeat domains of NUP98 in-frame to the HOXA9 homeobox. The predicted
      NUP98-HOXA9 fusion protein may promote leukaemogenesis through inhibition of
      HOXA9-mediated terminal differentiation and/or aberrant nucleocytoplasmic
      transport.

PMID- 8563755
TI  - Candidate gene acting as a suppressor of the RH locus in most cases of Rh
      deficiency.
AB  - The Rh antigen is a multi-subunit complex composed of Rh polypeptides and
      associated glycoproteins (Rh50, CD47, LW and glycophorin B); these interact in
      the red cell membrane and are lacking or severely reduced in Rhnull cells. As a
      result, individuals with Rhnull suffer chronic haemolytic anaemia known as the Rh
      deficiency syndrome. Most frequently, Rhnull phenotypes are caused by
      homozygosity of an autosomal suppressor gene unlinked to the RH locus (Rhnull
      regulator or Rhmod types). We have analysed the genes and transcripts encoding
      Rh, CD47 and Rh50 proteins in five such unrelated Rhnull cases. In all patients,
      we identified alteration of Rh50--frameshift, nucleotide mutations, or failure of
      amplification--which correlated with Rhnull phenotype. We propose that mutant
      alleles of Rh50, which map to chromosome 6p11-21.1, are likely candidates for
      suppressors of the RH locus accounting for most cases of Rh-deficiency.

PMID- 8563756
TI  - Efficient modification of human chromosomal alleles using recombination
      proficient chicken/human microcell hybrids.
AB  - Targeted modification of human chromosomal alleles by homologous recombination is
      a powerful approach to study gene function, but gene targeting in mammalian cells
      is an inefficient process. In contrast, gene targeting in a chicken pre-B cell
      line, DT40, is highly efficient. We have transferred human chromosome 11 into
      DT40 cells by microcell fusion, and find that the resulting hybrids are
      recombination-proficient. In these cells, targeting efficiencies into the chicken
      ovalbumin locus were > 90% and into the human beta-globin and Ha-ras loci were 10
      15%. These modified human chromosomes can be transferred subsequently to
      mammalian cells for functional tests. This chromosome shuttle system allows for
      the efficient homologous modification of human chromosomal genes, and for
      subsequent phenotypic analyses of the modified alleles in different mammalian
      cell types.

PMID- 8563757
TI  - Chromosomal localization of long trinucleotide repeats in the human genome by
      fluorescence in situ hybridization.
AB  - Trinucleotide microsatellites are widespread in the human and other mammalian
      genomes. Expansions of unstable trinucleotide repeats have been associated so far
      with a number of different genetic diseases including fragile X, myotonic
      dystrophy (DM) and Huntington disease. While ten possible trinucleotides can
      occur at the DNA level, only CTG and CCG repeats are involved in the disorders
      described so far. However, the repeat expansion detection (RED) technique has
      identified additional large repeats of ATG, CCT, CTT, and TGG of potentially
      pathological significance in the human genome. We now show that conclusive
      information about the chromosomal localization of long trinucleotide repeats can
      be achieved in a relatively short time using fluorescence in situ hybridization
      (FISH) with biotin-labelled trinucleotide polymers. Large CTG expansions (> 1 kb)
      in DM and an unstable (CTG)306 repeat in a patient with schizophrenia were
      detected by eye through the microscope without electronic enhancement. Digital
      imaging was used to analyse the chromosomal distribution of long CCA and AGG
      repeats. Our results suggest that long trinucleotide repeats occur in the normal
      human genome and that the size of individual repeat loci may be polymorphic.

PMID- 8563758
TI  - Peg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein.
AB  - Genetic and embryological studies in the mouse demonstrated functional
      differences between parental chromosomes during development. This is due to
      imprinted genes whose expression is dependent on their parental origin. In a
      recent systematic screen for imprinted genes, we detected Peg3 (paternally
      expressed gene 3). Peg3 is not expressed in parthenogenones. In interspecific
      hybrids, only the paternal copy of the gene is expressed in the embryos,
      individual tissues examined in d9.5-13.5 embryos, neonates and adults. Peg3 mRNA
      is a 9 kb transcript encoding an unusual zinc finger protein with eleven widely
      spaced C2H2 type motifs and two groups of amino acid repeats. Peg3 is expressed
      in early somites, branchial arches and other mesodermal tissues, as well as in
      the hypothalamus. Peg3 maps to the proximal region of chromosome 7. Consistent
      with our findings, maternal duplication of the proximal chromosome 7 causes
      neonatal lethality. This region is syntenic with human chromosome 19q13.1-13.3
      (refs 10,11), where the genes for myotonic dystrophy and a putative tumour
      suppressor gene are located.

PMID- 8563759
TI  - Brca1 deficiency results in early embryonic lethality characterized by
      neuroepithelial abnormalities.
AB  - The breast and ovarian cancer susceptibility gene, BRCA1, has been cloned and
      shown to encode a zinc-finger protein of unknown function. Mutations in BRCA1
      account for at least 80% of families with both breast and ovarian cancer, as well
      as some non-familial sporadic ovarian cancers. The loss of wild-type BRCA1 in
      tumours of individuals carrying one nonfunctional BRCA1 allele suggests that
      BRCA1 encodes a tumour suppressor that may inhibit the proliferation of mammary
      epithelial cells. To examine the role of BRCA1 in normal tissue growth and
      differentiation, and to generate a potential model for the cancer susceptibility
      associated with loss of BRCA1 function, we have created a mouse line carrying a
      mutation in one Brca1 allele. Analysis of mice homozygous for the mutant allele
      indicate that Brca1 is critical for normal development, as these mice died in
      utero between 10 and 13 days of gestation (E10-E13). Abnormalities in Brca1
      deficient embryos were most evident in the neural tube, with 40% of the embryos
      presenting with varying degrees of spina bifida and anencephaly. In addition, the
      neuroepithelium in Brca1-deficient embryos appeared disorganized, with signs of
      both rapid proliferation and excessive cell death.

PMID- 8563760
TI  - Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that
      of human hepatic porphyria.
AB  - Acute intermittent porphyria (AIP) is a human disease resulting from a dominantly
      inherited partial deficiency of the heme biosynthetic enzyme, porphobilinogen
      deaminase (PBGD). The frequency of the trait for AIP is 1/10,000 in most
      populations, but may be markedly higher (1/500) in psychiatric patients. The
      clinical expression of the disease is characterized by acute, life-threatening
      attacks of 'porphyric neuropathy' that include abdominal pain, motor and sensory
      neurological deficits and psychiatric symptoms. Attacks are frequently
      precipitated by drugs, alcohol and low caloric intake. Identical symptoms occur
      in other hepatic porphyrias. To study the pathogenesis of the neurologic symptoms
      of AIP we have generated Pbgd-deficient mice by gene targeting. These mice
      exhibit the typical biochemical characteristics of human AIP, notably, decreased
      hepatic Pbgd activity, increased delta-aminolevulinic acid synthase activity and
      massively increased urinary excretion of the heme precursor, delta-aminolevulinic
      acid after treatment with drugs such as phenobarbital. Behavioural tests reveal
      decreased motor function and histopathological findings include axonal neuropathy
      and neurologic muscle atrophy.

PMID- 8563761
TI  - Differential regulation of telomerase activity and telomerase RNA during multi
      stage tumorigenesis.
AB  - Telomeres consist of short repeated sequences that are synthesized by telomerase,
      a ribonucleo-protein DNA polymerase. Telomerase activity is present in many
      tumours and not detected in many normal tissues. Telomere shortening in human and
      mouse tissues and primary cell cultures may be due to the absence of telomerase
      activity. To determine when telomerase is activated during tumour development and
      progression, we examined telomerase activity and expression of the recently
      cloned mouse telomerase RNA component (mTR) in two different transgenic mouse
      models of multi-stage tumorigenesis. These mouse models allow examination of many
      independent tumours from genetically identical individuals. These mice
      reproducibly develop pancreatic islet cell carcinoma and squamous cell carcinoma
      of the skin. In both carcinoma types, we detected telomerase activity only in
      late-stage tumours; in contrast, we found mTR levels were upregulated in the
      early preneoplastic stages, and further increased during progression.
      Surprisingly, mTR levels did not parallel the amount of telomerase activity
      detected and a subset of tumours lacked telomerase activity and yet expressed
      telomerase RNA. Regulation of telomerase activity may therefore be separable from
      expression of its RNA component. These results clearly demonstrate telomerase is
      activated in late stages of tumour progression, and show for the first time that
      the initial up regulation of telomerase RNA is an early event, concurrent with
      the hyperproliferation elicited by viral oncogenes.

PMID- 8563762
TI  - The methyl-CpG binding protein MeCP2 is essential for embryonic development in
      the mouse.
AB  - Vertebrate genomes are heavily methylated at cytosines in the sequence CpG. The
      biological role of this modification is probably mediated by DNA binding proteins
      that are either attracted to or repelled by methyl-CpG. MeCP2 is an abundant
      chromosomal protein that binds specifically to methylated DNA in vitro, and
      depends upon methyl-CpG for its chromosomal distribution in vivo. To assess the
      functional significance of MeCP2, the X-linked gene was mutated in male mouse
      embryonic stem (ES) cells using a promoterless gene-targeting construct
      containing a lacZ reporter gene. Mutant ES cells lacking MeCP2 grew with the same
      vigour as the parental line and were capable of considerable differentiation.
      Chimaeric embryos derived from several independent mutant lines, however,
      exhibited developmental defects whose severity was positively correlated with the
      contribution of mutant cells. The results demonstrate that MeCP2, like DNA
      methyltransferase, is dispensable in stem cells, but essential for embryonic
      development.

PMID- 8563763
TI  - Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg)
      syndrome.
AB  - Recent reports have described a distinct and recurrent pattern of systemic
      malformation that associates craniosynostosis and neurodevelopmental
      abnormalities with many clinical features of the Marfan syndrome (MFS), an
      autosomal dominant disorder of the extracellular microfibril caused by defects in
      the gene encoding fibrillin-1, FBN1 (ref. 8). Additional common findings include
      other craniofacial anomalies, hypotonia, obstructive apnea, foot deformity, and
      congenital weakness of the abdominal wall. So far, only 11 cases have been
      reported precluding the assignment of definitive diagnostic criteria. While it
      remains unclear whether these cases represent a discrete clinical entity with a
      single aetiology, they have been pragmatically grouped under the rubric Marfanoid
      craniosynostosis or Shprintzen-Goldberg syndrome (SGS). Because of the
      significant clinical overlap between MFS and SGS, we proposed that they may be
      caused by allelic mutations. We now report two SGS patients who harbour mutations
      in FBN1. While it remains unclear whether these mutations are sufficient for the
      clinical expression of the entire SGS phenotype, these data suggest a role for
      fibrillin-1 in early craniofacial and central nervous system development. Our
      recent observation that FBN1 transcript is expressed as early as the 8-cell stage
      of human embryogenesis is consistent with this hypothesis.

PMID- 8563764
TI  - Mutations in the founder of the MIP gene family underlie cataract development in
      the mouse.
AB  - The major intrinsic protein (MIP) of the vertebrate eye lens is the first
      identified member of a sequence-related family of cell-membrane proteins that
      appears to have evolved by gene duplication. Several members of the MIP family
      transport water (aquaporins), glycerol and other small molecules in microbial,
      plant and animal cells. Mutations in two aquaporin homologues of MIP underlie an
      autosomal recessive form of nephrogenic diabetes insipidus and absence of the
      Colton blood group antigens in humans, whereas, mutation of a third MIP-like gene
      underlies 'big brain' development in Drosophila. Here we show that distinct
      mutations in the murine Mip gene underlie one form of autosomal dominant cataract
      in the mouse. The cataract Fraser mutation is a transposon-induced splicing error
      that substitutes a long terminal repeat sequence for the carboxy-terminus of MIP.
      The lens opacity mutation is an amino-acid substitution that inhibits targeting
      of MIP to the cell-membrane. These allelic cataract mutations provide the first
      direct evidence that MIP plays a crucial role in the development of a transparent
      eye lens.

PMID- 8563765
TI  - Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause
      glucose-galactose malabsorption.
AB  - Cotransporters harness ion gradients to drive 'active' transport of substrates
      into cells, for example, the Na+/glucose cotransporter (SGLT1) couples sugar
      transport to Na+ gradients across the intestinal brush border. Glucose-Galactose
      Malabsorption (GGM) is caused by a defect in SGLT1. The phenotype is neonatal
      onset of diarrhea that results in death unless these sugars are removed from the
      diet. Previously we showed that two sisters with GGM had a missense mutation in
      the SGLT1 gene. The gene has now been screened in 30 new patients, and a
      heterologous expression system has been used to link the mutations to the
      phenotype.

PMID- 8563766
TI  - Role of cytochrome P4501A2 in chemical carcinogenesis: implications for human
      variability in expression and enzyme activity.
AB  - Cytochrome P4501A2 (CYP1A2) has been identified as a key factor in the metabolic
      activation of numerous chemical carcinogens, including aflatoxin B1, various
      heterocyclic and aromatic amines, and certain nitroaromatic compounds. In
      addition, CYP1A2 contributes to the inactivation of several common drugs and
      dietary constituents, including acetaminophen and caffeine. Two xenobiotic
      responsive-element (XRE)-like sequences and an antioxidant response element (ARE)
      have been identified in the regulatory region of the CYP1A2 gene; however, the
      functionality of the ARE remains to be demonstrated. Based on in vivo phenotyping
      assays, substantial interindividual variability in CYP1A2 activity has been
      reported. Some population-based studies have reported either bi- or tri-modal
      distributions in CYP1A2 phenotype, suggesting a genetic basis for the large
      interindividual differences in CYP1A2 activity. However, despite the polymodal
      distributions reported for CYP1A2 activity, a distinct functional genetic
      polymorphism in the gene has not been identified. Potential mechanisms
      contributing to the large interindividual variability in CYP1A2 activity are
      discussed. A thorough understanding of the functions and regulation of the CYP1A2
      gene may ultimately lead to new methods for preventing or intervening in the
      development of certain chemically-related human cancers.

PMID- 8563767
TI  - Frequency of mutant CYP1A1, NAT2 and GSTM1 alleles in normal Indians and Malays.
AB  - Several xenobiotic metabolizing enzymes, including CYP1A1, NAT2 and GSTM1, are
      subject to genetic polymorphisms. Because these enzymes are important for the
      detoxification and/or bioactivation of drugs and carcinogens, these polymorphisms
      have important implications in therapeutics and cancer susceptibility. The
      distributions of CYP1A1, NAT2 and GSTM1 genotype frequencies in unrelated
      individuals of the Indian (n = 139) and Malay (n = 146) populations were
      characterized by the polymerase chain reaction. The respective allelic
      frequencies of wild-type and mutant alleles of CYP1A1 were 0.82 and 0.18 for the
      Indians, and 0.69 and 0.31 for the Malays. The frequencies of wild-type, M1, M2
      and M3 of NAT2 among Indians were 0.44, 0.20, 0.32 and 0.04 respectively. The
      corresponding NAT2 allelic frequencies in Malays were 0.41, 0.12, 0.38 and 0.09.
      The GSTM1*A allele could not be amplified in 33.1% of Indians and 61.6% of
      Malays. At least one GSTM1*B allele was detected in 7.2% and 7.5% of the
      respective populations. The allelic frequencies of CYP1A1, NAT2 and GSTM1 among
      Malays are similar to previously reported frequencies among Chinese in the
      region. These findings will be of importance in the determination of cancer risks
      in these populations.

PMID- 8563768
TI  - Higher activity of polymorphic thiopurine S-methyltransferase in erythrocytes
      from neonates compared to adults.
AB  - Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of aromatic and
      heterocyclic sulfhydryl compounds, including thiopurine antimetabolites (i.e.
      mercaptopurine and thioguanine). The activity of TPMT in erythrocytes and other
      tissues exhibits genetic polymorphism, which is inherited as an autosomal
      codominant trait. Although inheritance is the principal determinant of TPMT
      activity, other factors (e.g. renal function, race and thiopurine therapy) have
      been shown to influence erythrocyte TPMT activity. Because the TPMT polymorphism
      has not been established in early erythrocyte populations, and the activity of
      many enzymes differs in neonates, we determined the activity of TPMT in
      erythrocytes obtained from 60 full-term newborns. Median peripheral blood TPMT
      activity was 25.3 U per ml pRBC (range 9-52.8 U per ml pRBC), which was > 50%
      higher than race matched healthy adults (p < 0.001). Western blot analysis
      demonstrated higher TPMT protein content in erythrocytes from newborns compared
      to adults, and revealed a significant correlation between TPMT protein and TPMT
      activity in erythrocytes (rs = 0.63, p = 0.03). Although erythrocyte TPMT
      activity was significantly higher in newborns, the distribution of activity in
      newborns was consistent with the genetic polymorphism previously observed in
      adults.

PMID- 8563769
TI  - Interindividual variability in the glucuronidation of (S) oxazepam contrasted
      with that of (R) oxazepam.
AB  - Although conjugation with glucuronic acid is a major process for converting many
      xenobiotics into hydrophilic, excretable metabolites, relatively little has been
      reported concerning interindividual variability of glucuronidation in human
      populations. Oxazepam, a therapeutically active metabolite of diazepam, is one of
      a number of C3-hydroxylated benzodiazepines for which glucuronide conjugation is
      the predominant pathway of biotransformation. The drug is normally formulated as
      a racemic mixture of inactive (R) and active (S) enantiomers. In the present
      study we have investigated the use of oxazepam as a potential probe drug for
      studying the variability of glucuronide conjugation, and for demonstrating the
      extent to which genetic factors may be responsible. In preliminary studies we
      determined oxazepam pharmacokinetics metabolite profiles after administration of
      racemic (R,S) oxazepam to eleven human volunteers. The (S) glucuronide was
      preferentially formed and excreted in nine of the eleven subjects. The ratios of
      (S) to (R) glucuronide metabolites (S/R ratios) were 3.87 +/- 0.79 (mean +/- SD)
      and 3.52 +/- 0.60 in urine and plasma, respectively. However, both ratios were
      significantly lower in two subjects (p < 0.01). In these two atypical subjects,
      the half-life of (R,S) oxazepam was also markedly longer (14.7 and 15.9 h) than
      in the other subjects (8.1 +/- 3.2 h). A good correlation (rs = 0.90) between the
      S/R-glucuronide ratio in urine and the plasma clearance of (R,S) oxazepam
      suggested that a low S/R ratio may be a marker of poor elimination of oxazepam.
      In further investigations, the drug was administered to 66 additional subjects.
      The S/R-glucuronide ratio in 8 h pooled urine was bimodally distributed, with 10%
      of all subjects possessing ratios below an apparent antimode of 1.9. A survey of
      the in vitro formation of oxazepam glucuronides by microsomes from 37 human
      livers also showed that 10% of the livers displayed an abnormally high apparent
      Michaelis constant (Km) for the formation of the (S) glucuronide, but not of the
      (R) glucuronide. These results suggest that the glucuronidation of the
      pharmacologically active (S) enantiomer of oxazepam is decreased in a significant
      percentage (10%) of Caucasian individuals. The observed in vitro differences in
      apparent kinetics of the S-glucuronidation reaction may reflect defects at the
      genetic level, leading to structural changes in the isozyme(s) of UDP
      glucuronyltransferase that catalyse this reaction.

PMID- 8563770
TI  - Cytochrome P450 2E1 genotype and chlorzoxazone metabolism in healthy and
      alcoholic Caucasian subjects.
AB  - Susceptibility to cancer or ethanol-related liver diseases may be associated with
      a large variability in cytochrome P450 2E1 activity. This variability may be of
      genetic origin or reflect environmental factors. To test the role of genetics,
      the phenotype and genotype of this enzyme were determined in 42 non-alcoholic and
      74 alcoholic patients hospitalized for detoxification treatment. Chlorzoxazone
      metabolism was used to assess CYP2E1 phenotype. Restriction length fragment
      polymorphisms with Rsa I or Pst I, and Dra I endonucleases were used to determine
      the two mutant alleles, Pst I/Rsa I-c2 and Dra I-C. A significant gender
      difference in basal CYP2E1 activity was observed in non-smoking controls (p <
      0.05) but not in alcoholics or smokers. Subjects heterozygous for the C or c2
      mutated allele did not show any difference in CYP2E1 activity at the basal level,
      compared with the wild type homozygotes. Conversely, patients with the mutated
      genotype appeared less inducible than the others after ethanol induction (p <
      0.01).

PMID- 8563771
TI  - A novel CYP2D6 allele with an abolished splice recognition site associated with
      the poor metabolizer phenotype.
AB  - A novel loss-of function allele of the CYP2D6 gene was characterized in a PM
      individual using exon-by-exon PCR-SSCP analysis. This allele, we termed
      CYP2D6(F), harbours four mutations including a new mutation (D6-F) which
      abolishes the splice acceptor site of the 1st intron and results in a premature
      stop codon. DNA samples from a large population of healthy unrelated volunteers
      were tested for D6-F using a PCR-assay we developed for the specific
      identification of the mutation in genomic DNA. The prevalence of D6-F was very
      low. However, its identification combined with that of the previously reported
      gene inactivating mutations would further increase the phenotype prediction rate
      by genotyping.

PMID- 8563773
TI  - Genetic variation of CNS receptors--a new perspective for pharmacogenetics.

PMID- 8563772
TI  - A multifamily study on the relationship between CYP2C19 genotype and s
      mephenytoin oxidation phenotype.
AB  - It has recently been shown that the most common mutation (named m1) in both
      Caucasian and Japanese poor metabolizers (PM) of S-mephenytoin is a single base
      pair mutation (G-->A) in exon 5 of the CYP2C19 gene. In Japanese, a second
      defective allele of CYP2C19 named m2 consists of a G-->A mutation in exon 4. In
      the present study, we have investigated the inheritance of the CYP2C19 wild type
      allele (wt) and the two defective alleles (m1 and m2) in families of 11 Danish PM
      probands. The study was carried out for two principal reasons. First, we wanted
      to confirm the autosomal recessive inheritance of the defective alleles, and
      second, we wanted to examine the specificity and sensitivity of the CYP2C19
      genotyping test. Individuals were phenotyped by measuring the ratio of S/R
      mephenytoin excreted in the urine after administration of mephenytoin, and
      genotyping was carried out by a PCR-based DNA amplification procedure. The
      genotypes of nine of the 11 probands were consistent with their phenotypes. Eight
      were homozygous m1/m1, and one was heterozygous m1/m2. The genotypes of two
      putative PM probands (wt/m1) were not consistent with their phenotypes. On the
      basis of extended phenotyping (additional late urine collections (24-36 h) and
      acidification of urine), one of these could probably be reclassified as an
      extensive metabolizer (EM) while the other was considered to be a true PM. This
      suggests the presence of an additional unknown mutant allele in the latter. Seven
      of the 41 phenotyped relatives in the 11 families were phenotyped as PMs, and
      with the exception of the father of family 10, their genotypes (m1/m1) were
      consistent with their phenotypes. Extended phenotyping (acidification of urine)
      suggested that the father of family 10 in fact is an EM and hence that his
      genotype (wt/m1) is concordant with his phenotype. Thus, the specificity of
      genotyping tests for PM was 100%, while the sensitivity was 15/16 or 94%. Our
      study provides unequivocal evidence for autosomal recessive inheritance of the PM
      trait.

PMID- 8563774
TI  - Distribution of neuronal nicotinic acetylcholine receptor gene restriction
      fragment length polymorphisms in inbred and partially inbred mice.

PMID- 8563775
TI  - Glutathione S transferase-theta (GSTT1) genetic polymorphism among Chinese,
      Malays and Indians in Singapore.
AB  - Glutathione S-transferase-theta (GSTT1) is subject to a genetic polymorphism
      where approximately 50% of a Caucasian population are homozygous for the null
      allele. Because of the possible association of the polymorphism with increased
      cancer risk in individuals, we genotyped by polymerase chain reaction 187 normal
      Chinese, 167 normal Malays and 152 normal Indians from Singapore and Malaysia.
      The proportion of Chinese, Malays and Indians with the null genotype were 58%,
      38% and 16% respectively and mirrored previously reported frequencies of the
      GSTM1 null genotype in these populations. The frequency of the combined GSTM1 and
      GSTT1 null genotypes among Chinese, Malays and Indians were 37%, 22% and 5%
      respectively. The similarity with predicted frequencies indicated no interaction
      between the two genetic polymorphisms.

PMID- 8563776
TI  - The perceptions of stutterers by people who stutter.
AB  - Twenty-five persons who stutter completed a questionnaire asking respondents to
      list adjectives describing four hypothetical stutterers: a female child, male
      child, female adult and male adult stutterer. The majority of reported adjectives
      concerned negative stereotypical personality traits, indicating descriptions of
      stutterers by a group of persons who stutter that were similar to descriptions
      given by fluent subject groups. Implications of these findings are discussed.

PMID- 8563777
TI  - Vocal load as measured by the voice accumulator.
AB  - Voice disorders related to occupation and work environment are often observed in
      ENT consultations. Advising these patients requires not only the investigation of
      their vocal capacities but also knowledge about their vocal load. The patient
      will name extreme demands as the reason for vocal problems whereas the employer
      will want to know if the patient is capable of doing the work required of him.
      For an objective measurement of vocal load, a voice accumulator has been
      developed. This portable instrument records total speaking time and sound level
      over a period of several hours. The data can be transferred to a personal
      computer which analyses voiced time (s) between 60 and 112 dB(A)s. Thus, more
      precise and objective documentation of vocal demands in some professions can
      finally be obtained. With these results, it is possible to monitor vocal ability
      or disability during vocal rehabilitation.

PMID- 8563778
TI  - Aetiologic factors associated with hoarseness in ten-year-old children.
AB  - The parents of 55 10-year-old children answered questionnaires concerning 51
      elements of potential relevance to voice function such as vocal habits, speech
      and language development, medical history, social history, physical environment
      and family relations. In addition, personality profiles of each child were
      assessed by its teacher and parents. The results were compared to an expert
      listening panel's evaluation of hoarseness and vocal-fold status as determined by
      a visual examination by a phoniatrician. Eight boys were identified as being
      chronically hoarse. Gender, personality and hours spent per day in large groups
      were highly significant factors associated with hoarseness. A discriminant
      analysis based on the significant background variables correctly grouped 86.3% of
      the children.

PMID- 8563779
TI  - Acoustic parameters for the evaluation of voice of future voice professionals.
AB  - The authors tried to establish quantitative and qualitative acoustic parameters
      of a good voice, suitable for future voice professionals. In their work they used
      long-time average spectrum analysis (LTAS) and three-dimensional analysis of
      periodicity (3D-PAN). They consider the regression straight line of formant
      regions and the parameters offered by 3D-PAN--jitter first of all--as the main
      acoustic parameters for the evaluation of voice quality and draw attention to the
      fact that acoustic parameters represent only one part of the evaluation of voice
      quality.

PMID- 8563780
TI  - Trends in voice rehabilitation in the United Kingdom.
AB  - Three main basic forms of vocal rehabilitation are available for post
      laryngectomy patients in this country: oesophageal, mechanical vibrator and
      valved speech. In Sheffield, we advocate the use of valved speech, and insertion
      of the prosthesis preferably at the time of laryngectomy. We studied current
      vocal rehabilitation trends in the United Kingdom by a random survey of 100
      consultant otolaryngologists and present our findings here. While all forms of
      vocal rehabilitation are provided in the majority of centres, 20% of units
      involved in head and neck surgery do not have optimum levels of speech therapy
      involvement.

PMID- 8563781
TI  - Comparative analysis of singer's high formant in different type of singing
      voices.
AB  - The presence of singer's high formant (SHF) in singers of different musical
      styles was investigated. The voices of 10 opera, 8 folk, 4 pop singers and 53
      (non-singing) controls were recorded. The vowel 'a' was sung in three different
      registers. The percent of energy in the range of SHF and the stability of the
      pitch period generation were evaluated. The signals of all the singers are
      characterized by very high stability of the pitch period generation (> 99%), but
      their formant structures differ considerably. Energy concentration in the range
      of SHF is 23, 16, 7 and < 4% for opera, folk and pop singers and the controls,
      respectively.

PMID- 8563782
TI  - Heat shock protein 70 mRNA levels in mononuclear blood cells from patients with
      dementia of the Alzheimer type.
AB  - The heat shock protein 70 (HSP70) gene is located in chromosome 14, it is now
      considered as a molecular 'chaperone' and a cell-protective agent. It may be
      closely related to the pathogenesis of dementia of the Alzheimer type (DAT). To
      examine the relationship between HSP70 and DAT, HSP70 mRNA expression levels in
      mononuclear blood cells (MBCs) from patients with DAT were measured by Northern
      blotting. We found no significant correlation between HSP70 mRNA levels and
      aging. We found that HSP70 mRNA levels in MBCs from patients with DAT were
      significantly lower than those from patients with vascular dementia and
      nondemented controls. These findings suggest that the lower levels of
      constitutive HSP70 mRNA in DAT play an important role in developing DAT and that
      the measurement of HSP70 mRNA may be useful for the diagnosis of DAT.

PMID- 8563783
TI  - Chromogranin A in cerebrospinal fluid: a biochemical marker for synaptic
      degeneration in Alzheimer's disease?
AB  - Biochemical markers for AD would be of great value both to improve the clinical
      diagnostic accuracy in scientific studies and to increase the knowledge of the
      pathogenesis of the disorder. One of the main features of AD is a degeneration of
      synapses. Therefore, we examined if chromogranin A (CrA), the major protein of
      large dense-core synaptic vesicles, in cerebrospinal fluid (CSF) may be of value
      as a biochemical marker for the synaptic function in AD. The mean concentration
      of CrA in CSF was about 7.5 times higher than its concentration in serum, and
      there was no significant correlation between CSF-CrA and the blood-brain barrier
      function (measured as the CSF/serum albumin ratio), nor between CSF-CrA and serum
      CrA. These findings suggest that the major portion of CSF-CrA is locally produced
      within the CNS. There were no significant differences in CSF-CrA between the AD
      (n = 29), vascular dementia (n = 13), and age-matched control (n = 9) groups
      (99.9 +/- 58.9 ng/ml, 108.0 +/- 69.4 ng/ml, and 115.1 +/- 44.4 ng/ml,
      respectively). However, when the AD group was subdivided into AD type I (n = 12)
      and AD type II (n = 17), a lower concentration of CSF-CrA was found in AD type I
      (72.8 +/- 28.9 ng/ml) compared with controls (115.1 +/- 44.4 ng/ml), p < 0.02,
      and compared with AD type II (119.1 +/- 67.5 ng/ml), p < 0.05, while CSF-CrA did
      not significantly differ between AD type II and controls. These findings suggest
      that CSF-CrA has a potential as a biochemical marker for the synaptic
      degeneration in AD type I, and gives further support for the relevance of
      identifying the AD type I (pure AD) subgroup in scientific studies.

PMID- 8563784
TI  - Cognitive performance after small strokes correlates with ischemia, not atrophy
      of the brain.
AB  - Computerized tomographic measures of recurrent cerebral infarctions, atrophy and
      local perfusion were all prospectively correlated with cognitive testing during
      treatment of risk factors plus antiplatelet therapy among vascular dementia
      patients. Neurological and cognitive status were quantified among 22 demented
      patients with small strokes and compared with 22 age-matched normal volunteers.
      In vascular dementia, risk factor control plus antiplatelet therapy reduced
      cerebral infarctions, increased perfusion, and stabilized or improved cognitive
      test performance, despite age-related, progressive cerebral atrophy.

PMID- 8563785
TI  - EEG findings in dementia are related to the parietal lobe syndrome.
AB  - EEG indicators were correlated with clinical items in 174 patients with dementia
      diagnoses based on the DSM-III-R criteria. The patients' clinical
      symptomatologies were presented as regional brain syndromes, i.e. parietal lobe,
      frontal lobe, subcortical and global (nonregional) syndromes. The EEGs were
      abnormal in 87% of the cases. The typical abnormalities consisted of diffusely
      distributed slow wave activity. A significant correlation was found between the
      degree of slow wave abnormality and the degree of dementia. The results of the
      statistical analysis also suggest that EEG slow wave activity in dementia
      primarily reflects parietal lobe dysfunction. No association seems to exist
      between EEG slow wave activity and frontal lobe dysfunction.

PMID- 8563786
TI  - Number of platelet dense granules varies with age, schizophrenia and dementia.
AB  - In the present study we observed that the number of dense granules per platelet
      increases with age, attaining a maximum level above the age of about 40 years.
      Platelets of newborns apparently contain only a small number of dense granules
      per platelet. The numbers of platelet dense granules and platelet cell size in
      schizophrenic patients increase compared to age-matched healthy controls. In
      contrast, in Alzheimer-type dementia the number of platelet dense granules tends
      to decrease compared to healthy persons.

PMID- 8563787
TI  - Alzheimer's disease: distribution of changes in intraneuronal lipopigment in the
      frontal cortex.
AB  - Brains from 22 patients with Alzheimer's disease (AD) and 20 non-diseased
      subjects were examined. Intraneuronal lipopigment in 2,440 nucleolated neurons
      throughout the depth of cortex was identified by fluorescence microscopy. In the
      AD brains, the mean total area per neuron of the outlines of lipopigment was
      significantly increased in the region adjacent to the brain surface (sixths 1-3),
      and analysis of variance showed a significant interaction between depth of cortex
      (in sixths) and AD for this lipopigment variable (p = 0.012). After relating this
      lipopigment variable to the size of neuronal bodies, the results indicate that
      this change occurs in pyramidal neurons, although other neuronal types may also
      be affected. At least one of three AD-related changes in lipopigment was found in
      each sixth of the depth of cortex.

PMID- 8563788
TI  - Electroencephalographic correlates of periventricular white matter lesions in
      probable Alzheimer's disease.
AB  - We evaluated the relationship between periventricular white matter lesions
      (PWMLs) and EEG abnormalities in probable Alzheimer's disease (AD). We visually
      analyzed the EEG of 27 probable AD patients with mild to moderate degree of
      cognitive impairment participating in a longitudinal study of dementia. Patients
      had both CT and MRI scans performed at baseline examination, which also included
      an EEG. PWMLs were rated in CT and MRI films using a semiquantitative method. The
      EEGs were classified according to the Mayo Clinic Classification System. Abnormal
      EEGs correlated with PWMLs rating scores were detected on CT, but not on MRI.
      These data suggest that the presence of PWMLs contribute to the abnormal EEGs
      observed in AD patients, and that white matter abnormalities in CT correlate
      better with both the clinical findings and EEG than does the more sensitive but
      less specific MRI.

PMID- 8563789
TI  - Evidence of blood-cerebrospinal fluid-barrier impairment in a subgroup of
      patients with dementia of the Alzheimer type and major depression: a possible
      indicator for immunoactivation.
AB  - Serum and cerebrospinal fluid (CSF) from 44 patients with clinical probable
      Alzheimer's disease (AD) (subdivided in two groups with 18 early onset, EO, and
      26 late onset, LO, cases), 10 patients with vascular dementia (VD) and 24
      patients with major depression (MD) were assayed for concentrations of albumin
      and IgG. The severity of dementia was assessed with the Mini Mental State
      Examination. The CSF/serum ratio for albumin and IgG as well as the IgG index
      were used to evaluate blood-CSF barrier function. Various patients showed signs
      of blood-CSF-barrier (BCB) dysfunction and only few displayed evidence of local
      IgG synthesis in the central nervous system (CNS) in the AD, VD and in the MD
      group (IgG index > 0.7). The permeability of the blood-CSF barrier was not
      correlated to measures of dementia severity. Our data support the hypothesis of a
      BCB leakage in a subgroup of all investigated patients. Furthermore, we found a
      small number of patients with increased intrathecal IgG synthesis. Elevated CSF
      immunoglobulins combined with BCB impairment might be associated or caused by a
      general immune activation. Our data are in agreement with the assumption that an
      inflammatory process may play a role in a subgroup of patients with AD but also
      with MD and less likely in VD. In conclusion BCB impairment and elevated IgG
      immunoglobulin levels are unspecific either for AD, VD or MD.

PMID- 8563790
TI  - Cumulative risk of Alzheimer-like dementia in relatives of autopsy-confirmed
      cases of Alzheimer's disease.
AB  - The cumulative risk of Alzheimer-like dementia (AD) was investigated in first
      degree relatives (n = 176) of 35 probands with autopsy-confirmed clinical
      diagnoses of Alzheimer's disease. Seventeen of the 176 first-degree relatives
      showed evidence of AD. Cumulative morbid risk for the first-degree relatives was
      estimated to be 28.8%. This result is broadly consistent with previously reported
      studies, and affirms the presence of substantial disease risk in close relatives
      of those with Alzheimer's disease.

PMID- 8563791
TI  - Characterization of Na,K-ATPase isoform expression and activity in MDCK and Caco
      2 epithelial cells.
AB  - The asymmetric distribution of the Na,K-ATPase in the plasma membrane of
      epithelial cells is essential to the establishment of the transepithelial Na+
      gradient that supports the vectorial transport of ions and solutes. To
      investigate the changes that occur during the development of polarity, we have
      characterized Na,K-ATPase expression and activity in two epithelial cell culture
      lines, Madin Darby canine kidney (MDCK) and Caco-2 cells. RNA and immunoblot
      analysis of both cell lines demonstrate that only the alpha 1 and beta 1 isoforms
      are expressed in nonpolarized and polarized cultures. Interestingly, alpha 1 and
      beta 1 message increases in MDCK cells with the development of polarity, yet
      there is little change in the amount of protein for either subunit. In contrast,
      alpha 1 and beta 1 polypeptide expression increases in Caco-2 cells with the
      development of polarity, even though the amount of both transcripts decreases.
      The lack of correlation between the changes that occur at the level of the
      message and protein suggest that appropriate expression is mediated in part by a
      combination of transcriptional and translational events. Furthermore, while there
      was a slight decrease in activity in polarized MDCK cells, there was a 1.9 fold
      increase in Na,K-ATPase activity in the polarized Caco-2 cells as compared to
      nonpolarized cells. These results demonstrate that the regulation of Na,K-ATPase
      alpha 1 and beta 1 isoform expression is mediated by a combination of
      transcriptional and translational events during the development of polarity in
      both cell lines.

PMID- 8563792
TI  - Topical application of retinoic acid induces murine epidermal proliferation
      without reducing the cell cycle time. A bivariate BrdUrd/DNA flow cytometric
      study.
AB  - Topical application of retinoic acid (RA) induces skin irritation, increased
      epidermal DNA synthesis and hyperplasia by an unknown mechanism, possibly in
      common with other hyperplasiogens. To further characterize this regeneration-like
      effect of RA, the cell cycle traverse in hairless mouse epidermis in vivo after
      application of a single dose of 100 nmol RA was investigated. Two BrdUrd labelled
      basal cell cohorts, one exposed to RA during the S phase, the other stimulated by
      RA into S phase 16 h earlier, were followed for 30 h in their progression through
      the cell cycle. The basal cells were isolated and prepared for bivariate
      BrdUrd/DNA flow cytometry analysis (FCM). Both cohorts showed induced
      proliferation of cells stimulated from G0/G1 into S phase as shown by increase in
      the S phase fraction, but without reduction in cell cycle time as expected for
      regenerative growth. This implies that RA stimulates proliferation differently
      than other hyperplasiogens, and hence may induce irritation and growth
      stimulation through another mechanism.

PMID- 8563793
TI  - Assessment of inflammatory events in epithelial permeability: a rapid screening
      method using fluorescein dextrans.
AB  - Cultured intestinal epithelial monolayers serve as models for mechanistic studies
      of intestinal inflammation. One crucial aspect of epithelial function modulated
      by inflammation is permeability. Indices of permeability typically obtained are
      transepithelial resistance or more formalized assays using Ussing chambers
      modified for cultured monolayers. Such Ussing chamber systems are inconvenient
      for screening assays and their geometry precludes evaluation of important
      inflammatory responses such as transepithelial migration of neutrophils. Here we
      use a novel flux assay to investigate the kinetics of fluorescein-labelled
      dextran (FD) molecules across intestinal epithelial cell lines grown on permeable
      membrane supports. Our results show that we could consistently demonstrate
      picomolar flux of FD in a range of sizes (3-70 kD) across T84 epithelial
      monolayers. Such FD flux was time- and dose-dependent and flux increased
      exponentially with decreasing transepithelial resistance. Exposure of intestinal
      epithelia to mucosal-derived lymphocytes or to soluble lymphocyte products
      (interferon-gamma, interleukin-4 or interleukin-13) increased FD flux in a dose
      dependent fashion. Finally, studies of neutrophil transepithelial migration
      revealed qualitative and quantitative differences in FD flux depending on FD
      size. We conclude that in vitro transepithelial FD flux may be a useful tool to
      study aspects of intestinal permeability in health and in disease.

PMID- 8563794
TI  - Activators of protein kinase C but not of phospholipase C modulate adenylate
      cyclase-responses of normal pig epidermis.
AB  - It has been reported that keratinocytes possess phospholipase C (PLC)-mediated
      signal transduction system(s), that can be triggered by histamine, bradykinin,
      thrombin, platelet-activating factor (PAF), and epidermal growth factor
      (EGF)/transforming growth factor-alpha (TGF-alpha). Since the activation of PLC
      results in release of 1,2-diacylglycerol (DAG), the physiologic activator of
      protein kinase C (PKC) that modulates the epidermal adenylate cyclase, we
      investigated the effects of these PLC activating chemicals on the adenylate
      cyclase responses of dispase-separated normal pig epidermis. Among these
      chemicals and factors only histamine decreased the successive histamine-induced
      cyclic AMP accumulation and increased forskolin-, and cholera toxin-induced AMP
      accumulations. These effects were similar to those of PKC activators. However, in
      contrast to the PKC-activator-induced partial and receptor-non-specific
      desensitization, the histamine-induced desensitization was completely-inducible
      and specific to the histamine receptor system, and was not affected by the PKC
      inhibitor, H-7. Similar modulation of the epidermal adenylate cyclase was induced
      by other adenylate cyclase stimulators (epinephrine, adenosine and prostaglandin
      E2), but not by bradykinin, thrombin, PAF, or EGF. The combined addition of
      bradykinin, thrombin, PAF and EGF to the culture medium had no effect on the
      adenylate cyclase responses, either. Thus no evidence for receptor-agonist
      dependent PLC-induced modulation of the adenylate cyclase was obtained in the
      normal pig epidermis. Although keratinocytes might contain PLC-mediated signal
      transduction systems, that are triggered by histamine, bradykinin, thrombin, PAF,
      and EGF/TGF-alpha, none of the activators singly or in combination appear to
      activate PKC sufficiently for the modulation of adenylate cyclase responses of
      the normal pig epidermis.

PMID- 8563795
TI  - Vectorial secretion by constitutive and regulated secretory pathways in mammary
      epithelial cells.
AB  - Lactating mammary epithelial cells synthesize large quantities of milk proteins,
      which they secrete vectorially at the apical membrane into the alveolar lumen of
      the gland. Recent work suggested that mammary protein secretion is not wholly
      constitutive, but may also occur in part through a regulated secretory pathway.
      This study used mouse mammary epithelial cells cultured on Engelbreth-Holm-Swarm
      (EHS) matrix to compare the proportions of basally and apically-directed proteins
      secreted constitutively or in a regulated manner. On EHS matrix, mammary cells
      formed mammospheres, multicellular structures enshrouded in matrix material,
      within which they became polarised, formed tight intercellular junctions, and
      secreted milk proteins vectorially. Protein secreted basolaterally was collected
      in culture medium, whereas apically-secreted milk proteins accumulated in a
      closed lumen within the mammosphere, and were recovered by EGTA treatment of the
      cells in situ. Protein secretion was measured by following the release of
      radiolabelled protein after pulse-labelling with [35S]-methionine. Basolateral
      and apical secretion of [35S]-protein appeared complete within 1 h of pulse
      labelling, consistent with immediate secretion through constitutive secretory
      pathways. However, addition of the calcium ionophore ionomycin induced a second
      wave of secretion in both directions. Ca(2+)-stimulated secretion occurred within
      15 min of ionomycin addition, doubled the extent of basolateral and apical
      secretion, but did not change the populations of proteins secreted. Ionomycin
      treatment did not affect mammosphere morphology or mammary cell ultrastructure.
      The results suggest that lactating mammary epithelial cells secrete proteins
      apically and basolaterally by two pathways, one a Ca(2+)-independent constitutive
      pathway, the other a regulated pathway stimulated by elevation of intracellular
      Ca2+.

PMID- 8563796
TI  - Tools for expressing foreign genes in plants.

PMID- 8563797
TI  - Gene transfer into plant protoplasts by electroporation.

PMID- 8563798
TI  - Transformation of cereals by microprojectile bombardment of immature
      inflorescence and scutellum tissues.

PMID- 8563799
TI  - The beta-glucuronidase (gus) reporter gene system. Gene fusions;
      spectrophotometric, fluorometric, and histochemical detection.

PMID- 8563800
TI  - Chloramphenicol acetyl transferase assay.

PMID- 8563801
TI  - NPTII assays for measuring gene expression and enzyme activity in transgenic
      plants.

PMID- 8563802
TI  - Gene characterization by southern analysis.

PMID- 8563803
TI  - Isolation and characterization of plant genomic DNA sequences via (inverse) PCR
      amplification.

PMID- 8563804
TI  - Isolation of whole cell (total) RNA.

PMID- 8563805
TI  - Poly(A)+ RNA isolation.

PMID- 8563806
TI  - In vitro translation.

PMID- 8563807
TI  - Northern analysis and nucleic acid probes.

PMID- 8563808
TI  - Nuclear "run-on" transcription assays.

PMID- 8563809
TI  - RNase A/T1 protection assay.

PMID- 8563810
TI  - Primer extension assay.

PMID- 8563811
TI  - Applications of RT-PCR.

PMID- 8563812
TI  - In vitro transcription of class II promoters in higher plants.

PMID- 8563813
TI  - Analysis of plant gene expression by reverse transcription-PCR.

PMID- 8563814
TI  - In situ hybridization to plant tissue sections.

PMID- 8563815
TI  - Xenopus oocytes as a heterologous expression system.

PMID- 8563816
TI  - Introduction of cloning plasmids into Agrobacterium tumefaciens.

PMID- 8563817
TI  - Heterologous expression in yeast.

PMID- 8563818
TI  - The isolation of intact chloroplasts.

PMID- 8563819
TI  - In vitro protein import by isolated chloroplasts.

PMID- 8563820
TI  - Targeting of foreign proteins to the chloroplast.

PMID- 8563821
TI  - Isolation of mitochondria.

PMID- 8563822
TI  - Mitochondrial nucleic acid purification and analysis.

PMID- 8563823
TI  - Leaf disk transformation using Agrobacterium tumefaciens-expression of
      heterologous genes in tobacco.

PMID- 8563824
TI  - In organello protein synthesis.

PMID- 8563825
TI  - Separation of plant proteins by electrophoresis.

PMID- 8563826
TI  - Western blotting analysis.

PMID- 8563827
TI  - ELISA detection of foreign proteins.

PMID- 8563828
TI  - Immunocytochemical localization of proteins.

PMID- 8563829
TI  - Agrobacterium rhizogenes as a vector for transforming higher plants. Application
      in Lotus corniculatus transformation.

PMID- 8563830
TI  - Agrobacterium-mediated transformation of Arabidopsis thaliana. Application in T
      DNA tagging.

PMID- 8563831
TI  - Agrobacterium-mediated transfer of geminiviruses to plant tissues.

PMID- 8563832
TI  - Stable transformation of barley via direct DNA uptake. Electroporation- and PEG
      mediated protoplast transformation.

PMID- 8563833
TI  - Perspectives in health economics.
AB  - This paper, originally presented at the Institute d'Etudes Politiques de Paris,
      October 12, 1993, provides a perspective on envisioned changes in the practice of
      health economics. Foreseen changes include: (1) Study of more homogeneous units
      of analysis; (2) More original data gathering; (3) Increased attention to
      uncertainty and the supply of and demand for information; (4) Increased attention
      to institutional structures and their effects on economic behaviour; (5)
      Expansion of relevant tools for studying economic issues in health care; and (6)
      Continuing breakdown of disciplinary barriers between health economics and other
      disciplines. Of these, the two overriding features will be increased emphasis on
      understanding the many roles of uncertainty in economic behaviour, institutions,
      and outcomes in health care, and in the use of more and more 'micro' data to
      study these issues.

PMID- 8563834
TI  - Sensitivity analysis in economic evaluation: a review of published studies.
AB  - A structured methodological review of journal articles published in 1992 was
      undertaken to determine whether recently published economic evaluation studies
      deal systematically and comprehensively with uncertainty. Ninety three journal
      articles were identified from a range of searches including a computerised search
      of the MEDLINE CD-Rom database. Articles were reviewed to determine how they had
      handled uncertainty in: a) data sources; b) generalisability; c) extrapolation;
      and d) analytic method. Articles were subsequently assessed to determine how they
      had represented this uncertainty in terms of the overall results of their
      analysis. Finally, studies were rated on the basis of their overall performance
      with respect to dealing systematically and comprehensively with uncertainty.
      Despite the numerous books and articles devoted to the appropriate methods to be
      employed by analysts conducting economic evaluation, 22 (24%) studies failed to
      consider uncertainty at all and 35 (38%) studies employed sensitivity analysis in
      a manner judged as inadequate. In all, 36 (39%) studies were judged to have given
      at least an adequate account of uncertainty with 13 (14%) of those judged to have
      provided a good account of uncertainty. Such disappointing results may reflect a
      general lack of detail in much of the methods literature concerning how
      sensitivity analysis should be applied and how results should be presented.
      Journal editors and readers of economic evaluation articles should acquaint
      themselves with the methods for handling uncertainty in order that they can
      critically evaluate the extent to which authors have allowed for uncertainties
      inherent in their analysis.

PMID- 8563835
TI  - Confidence intervals for cost/effectiveness ratios.
AB  - The reduction of costs is becoming increasingly important in the medical field.
      The relevant topic of many clinical trials is not effectiveness per se, but
      rather cost-effectiveness ratios. Surprisingly, no statistical tools for
      analyzing cost-effectiveness ratios have been provided in the medical literature
      yet. This paper explains the gap in the literature, and provides a first
      technique for obtaining confidence intervals for cost-effectiveness ratios. The
      technique does not use sophisticated tools to achieve maximal optimality, but
      seeks for tractability and ease of application while still satisfying all formal
      statistical requirements.

PMID- 8563836
TI  - Are guidelines for peer-reviewing economic evaluations necessary? A survey of
      current editorial practice.
AB  - We report the results of a postal survey of 150 editors of medical journals aimed
      at assessing editorial policy on peer-review of economic studies. 70 editors
      (47%) responded to the anonymous questionnaire which contained six questions. 16
      (23% or respondents) claimed to have an editorial policy, most claiming
      acceptance of 'good evaluations'. Few (36%) had trained economists as referees
      and none had criteria or guidelines for peer-reviewing economic studies. This
      situation helps to explain the variable quality of international economic
      literature. There is an urgent need to produce internationally accepted sets of
      guidelines for authors, editors and peer-reviewers.

PMID- 8563837
TI  - Performance of Belgian hospitals: a frontier approach.
AB  - The purpose of the paper is to measure and to compare performance of Belgian
      hospitals during the year 1991. In order to measure hospitals' efficiency, we
      estimate a resource function which is defined as the relationship between medical
      fees incurred in the treatment of a patient and the patient's pathology. From
      this relation, we construct a best practice reference frontier which defines the
      minimal hospital medical fees needed to treat the pathology. Efficiency is
      assessed relative to this resource frontier using a parametric stochastic method
      proposed by Schmidt and Sickles. It appears that some specializations
      (circulatory system) involve more overproduction than others. Among the other
      results, we note that public hospitals are more efficient than the private ones
      and that university hospitals tend to use more resources than regular hospitals.
      The relationships between efficiency and different variables (location, size,
      costs and management) are finally analysed.

PMID- 8563838
TI  - Controlling for mental health in earnings equations: what do we gain and what do
      we lose?
AB  - This paper examines the biases in estimating wage equations that may arise from
      measurement errors in various mental health indicators--two subjective proxies
      and one clinical assessment. The results suggest that a self-reported measure
      based on whether the individual reported missing school or work for mental-health
      related reasons leads to the smallest measurement error bias in the coefficients
      of the explanatory variables in an earnings equation. Two specific results lead
      to this conclusion. For one, the variance of the random component of its
      measurement error is the smallest among the three indicators leading to the least
      biased estimates of the impact of mental health on wages. Second, systematic
      reporting biases which vary with the non-health regressors in a wage equation do
      not appear to exit in this measure. Consequently, this indicator follows the
      classical measurement error model. This implies that the coefficient estimates of
      the impact of non-health variables are always improved, in the sense of having a
      smaller bias, when this mental health proxy is included in the regression. The
      measurement error in a self-evaluation according to the scale of excellent, good,
      fair, or poor has the largest variance thus leading to a substantial
      understatement of the impact of mental health on earnings. This measure also
      contains significant reporting biases that vary with gender, race, and education-
      many of the non-health regressors in a wage equation. The measurement error
      variance in the simulated diagnostic measure analyzed in this paper is also
      large. Thus this proxy will yield poor estimates of the impact of mental health
      on earnings.

PMID- 8563839
TI  - Investigation of disease risks in small areas.
AB  - The investigation of disease risks in small areas is complicated by many issues
      including data quality, the retrospective nature of the statistical testing, the
      problems of boundary definitions in time and space around a putative disease
      cluster, and the lack of generally accepted definitions of the key terminology.
      Routine data systems have revolutionised the initial investigation of disease
      risks near sources of environmental pollution, although problems of data analysis
      and interpretation remain. This is especially true of unmeasured socioeconomic
      confounding, which could generate apparent positive results near a pollution
      source.

PMID- 8563840
TI  - Individual exposure to particulate air pollution and its relevance to thresholds
      for health effects: a study of traffic wardens.
AB  - OBJECTIVE: To investigate the differences between measurements of personal
      exposure to particulate air pollution and static area measurements in a group of
      people working close to traffic and to determine whether such differences might
      obscure any threshold for health effects in epidemiological studies. METHODS:
      Personal air sampling was carried out on two groups of eight traffic wardens for
      four days on two consecutive weeks in November 1994. These measurements were
      compared with standard environmental static sampling data that were obtained for
      the same period. A simulation with log normal distributions of personal exposures
      was produced, and an arbitrary risk calculated for each exposure, assuming a
      threshold of 50 micrograms/m3, and an exposure-response curve was calculated.
      RESULTS: The median concentration for personal samplers in week 1 was 123
      micrograms/m3 and 41 micrograms/m3 in week 2. Corresponding area concentrations
      were 10 micrograms/m3 and 7.5 micrograms/m3. The differences between the personal
      and area results were significant, as were the differences for personal sampling
      between weeks 1 and 2. The simulation showed that the variation in individual
      exposures around an area sampler obscured the threshold. CONCLUSIONS: Area
      sampling data may be of limited value in the investigation of the biological
      effects of exposure to pollution and their use may result in real thresholds
      being obscured. Personal exposure assessment may be crucial in determination of
      the health effects attributable to different concentrations of air pollutants.

PMID- 8563841
TI  - Occupational exposure to inhalable and total aerosol in the primary nickel
      production industry.
AB  - OBJECTIVES: This paper describes a study that was carried out in the primary
      nickel production industry to investigate the levels of personal exposure to
      aerosols containing nickel and the impact on exposure assessment of introducing
      new personal sampling techniques with performance consistent with the latest
      particle size-selective criteria. METHODS: Experiments were carried out at
      workplaces in mining, milling, smelting, and refining works to investigate the
      effect of changing from the current method of total aerosol (with the widely used
      37 mm filter holder) to the new method of measuring inhalable aerosol (with the
      Institute of Occupational Medicine (IOM) inhalable aerosol sampler). RESULTS: The
      results show that inhalable aerosol exposure concentrations--for both overall
      aerosol and for total nickel--were consistently and significantly higher than the
      corresponding total aerosol concentrations. Weighted least squares linear
      regression yielded IOM/37 mm factors ranging from about 1.2 to 4.0. The exposure
      data for each company process were found to be log-normally distributed.
      CONCLUSIONS: The results suggest the possibility of generating a single pragmatic
      factor for each company process for converting current total aerosol exposures to
      new exposures based on the inhalability concept contained in the latest particle
      size-selective criteria for aerosol exposure assessment. Such data may be
      important in determining new occupational exposure limits for nickel.

PMID- 8563842
TI  - Chronic effects of welding exposure on pulmonary function tests and respiratory
      symptoms.
AB  - OBJECTIVES: The respiratory effects of exposure to welding fumes have been
      investigated in numerous studies; but results of these studies have not been
      consistent. The aim of the present study was to investigate the respiratory
      effects of welding exposure in a large group of manual are welders exposed
      primarily to mild steel welding processes in confined spaces without respiratory
      protection. METHODS: Respiratory symptoms and spirometry were studied in 110
      welders and 55 controls. The welders and controls were of similar average age and
      height; smoking habits of the groups were similar. Chest x ray films were taken
      to exclude people with radiological abnormalities that may influence pulmonary
      function tests. Welders were grouped according to smoking habits and duration of
      employment (< 20 years or > 20 years). RESULTS: No gross radiological
      abnormalities were found. Respiratory symptoms and chronic bronchitis were more
      prevalent in welders (P < 0.05). Welders who were smokers showed a higher
      frequency of chronic bronchitis than controls who smoked (P < 0.05). No
      significant difference in the occurrence of chronic bronchitis was found between
      welders who smoked and welders who were non-smokers or exsmokers. Compared with
      the controls, forced vital capacity (FVC), forced expiratory volume in one second
      (FEV1), peak expiratory flow (PEF), and maximum midexpiratory flow (MMEF) were
      significantly lower in welders (mean values of FVC for welders and controls were
      86.06 (25.74) and 96.40 (13.03); and values for FEV1 were 87.54 (13.70) and 95.36
      (12.40) respectively; P < 0.01). There was no significant difference in pulmonary
      function tests between welders who were non-smokers and controls who were non
      smokers; whereas FVC, FEV1, PEF, and MMEF were significantly lower in welders who
      smoked than controls who smoked (P < 0.01). There were no significant differences
      in pulmonary function tests and occurrence of chronic bronchitis between welders
      with more or less than 20 years at work. CONCLUSION: Welders working in
      conditions of inadequate ventilation, have increased risk of chronic bronchitis
      and impairment of pulmonary function.

PMID- 8563843
TI  - Mortality of copper cadmium alloy workers with special reference to lung cancer
      and non-malignant diseases of the respiratory system, 1946-92.
AB  - OBJECTIVES: To identify and quantify any relations between occupational exposure
      to cadmium oxide fume and mortalities from lung cancer and from chronic non
      malignant diseases of the respiratory system. METHODS: The mortality experience
      of 347 copper cadmium alloy workers, 624 workers employed in the vicinity of
      copper cadmium alloy work (vicinity workers), and 521 iron and brass foundry
      workers (all men) was investigated for the period 1946-92. All subjects were
      first employed in these types of work in the period 1922-78 and for a minimum
      period of one year at one of two participating factories. Two analytical
      approaches were used, indirect standardisation and Poisson regression. RESULTS:
      Compared with the general population of England and Wales, mortality from lung
      cancer among copper cadmium alloy workers was close to expectation (observed
      deaths 18, expected deaths 17.8, standardised mortality ratio (SMR) 101, 95%
      confidence interval (95% CI) 60 to 159). A significant excess was shown for lung
      cancer among vicinity workers but not among iron and brass foundry workers
      (vicinity workers: observed 55, expected 34.3, SMR 160, 95% CI 121 to 209, P <
      0.01; iron and brass foundry workers: observed 19, expected 17.8, SMR 107, 95% CI
      64 to 167). Increased SMRs for non-malignant diseases of the respiratory system
      were shown for each of the three groups (alloy workers: observed 54, expected
      23.5, SMR 230, 95% CI 172 to 300, P < 0.001; vicinity workers: observed 71,
      expected 43.0, SMR 165, 95% CI 129 to 208, P < 0.001; iron and brass foundry
      workers: observed 34, expected 17.1, SMR 199, 95% CI 137 to 278, P < 0.01). Work
      histories of the copper cadmium alloy workers were combined with independent
      assessments of cadmium exposures over time to develop individual estimates of
      cumulative exposure to cadmium; this being a time dependent variable. Poisson
      regression was used to investigate risks of lung cancer and risks of chronic non
      malignant diseases of the respiratory system in relation to three levels of
      cumulative cadmium exposure (< 1600, 1600-4799, > or = 4800 micrograms.m-3.y).
      After adjustment for age, year of starting alloy work, factory, and time from
      starting alloy work, there was a significant positive trend (P < 0.01) between
      cumulative exposure to cadmium and risks of mortality from chronic non-malignant
      diseases of the respiratory system. Relative to a risk of unity for the lowest
      exposure category, risks were 4.54 (95% CI 1.96 to 10.51) for the middle exposure
      category and 4.74 (95% CI 1.81 to 12.43) for the highest exposure category. There
      was a non-significant negative trend between cumulative cadmium exposure and
      risks of mortality from lung cancer. Relative to a risk of unity for the lowest
      exposure category, risks were 0.85 (95% CI 0.27 to 2.68) for the middle exposure
      category and 0.81 (95% CI 0.18 to 3.73) for the highest exposure category.
      Similar findings were obtained when adjustment was made for age only.
      CONCLUSIONS: The findings are consistent with the hypothesis that exposure to
      cadmium oxide fume increases risks of mortality from chronic non-malignant
      diseases of the respiratory system. The findings do not support the hypothesis
      that exposure to cadmium oxide fume increases risks of mortality for lung cancer.

PMID- 8563844
TI  - A pilot study of the effect of low level exposure to mercury on the health of
      dental surgeons.
AB  - OBJECTIVES: This project was conducted to examine whether the computerised
      analysis of psychomotor responses available from Cognitive Drug Research is
      appropriate for measuring an effect of low level exposure to mercury in dentists.
      METHODS: A computerised battery of psychomotor tests was given to two groups of
      dentists (older dentists and trainees) and to two age matched control groups. As
      well as the psychomotor tests, volunteers were required to complete a
      questionnaire to identify potential influences on psychomotor performance and to
      provide a sample for analysis of urinary mercury. RESULTS: Statistical analysis
      of the results showed that the older dentists had slightly higher concentrations
      of urinary mercury although most were around background levels and they were all
      within occupational limits. Five of the psychomotor tests showed no differences
      between the performance of the four groups. The older dentists showed
      significantly better performance on the simple reaction time test and
      significantly poorer performance in the immediate word recall and delayed word
      recall tests. CONCLUSIONS: Poorer performance in memory recall tests confirms
      previously reported studies. This together with the confirmation that this test
      system is a practical tool in the occupational setting suggests that a larger
      study of the effects of mercury exposure on dentists would be appropriate.

PMID- 8563845
TI  - Decreased glomerular filtration rate in solderers exposed to cadmium.
AB  - OBJECTIVES: to evaluate the degree of cadmium induced glomerular impairment and
      to assess the dose-response relation between cadmium dose and the prevalence of
      glomerular dysfunction. METHODS: A comparison of glomerular filtration rates
      (GFR) assessed by Cr-EDTA clearance was made in 42 solderers previously exposed
      to cadmium for at least five years. Blood and urine data were collected at health
      examinations in 1984, 1989, and 1993. Individual doses of cadmium were estimated
      by analysing cadmium in blood. RESULTS: Glomerular lesions induced by cadmium are
      irreversible and the GFR decreases with the degree of tubular damage. The GFR
      also decreases with cadmium dose and there is a dose-response relation between
      blood cadmium and prevalence of glomerular damage with 3.4% prevalence at blood
      cadmium concentrations below 50 nmol/l, 33% at blood cadmium concentrations
      between 50 and 75 nmol/l and 100% prevalence of glomerular damage when cadmium in
      blood exceeds 75 nmol/l. CONCLUSIONS: The kidney lesions induced by cadmium are
      irreversible and the prevalence of those lesions are dose dependent. There is
      also evidence of a dose related decrease in GFR even a long time after the end of
      exposure. Exposure to cadmium should therefore be minimised and workers exposed
      to cadmium should be examined regularly for many years after the end of exposure.

PMID- 8563846
TI  - Occupational exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans in a
      magnesium production plant.
AB  - OBJECTIVES: The production of magnesium is a well known source of both aliphatic
      and aromatic chlorinated compounds, among others the polychlorinated dibenzo-p
      dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The aim of this study
      was to establish whether increased concentrations of PCDDs and PCDFs could be
      found in the blood of workers in a magnesium plant. METHODS: Blood plasma from 10
      workers, employed at a magnesium plant for 10 to 36 years, and from a control
      group consisting of nine people who had no direct contact with the production
      were studied. Isomer specific analyses of PCDDs and PCDFs by means of high
      resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS)
      techniques were performed. RESULTS: A significant increase was found in the
      concentrations of some of the congeners, mainly PCDFs, in the workers compared
      with the control group. Octachlorodibenzofuran (OCDF) is the congener that most
      strongly correlates with occupational exposure in the magnesium plant. Low
      concentrations of 1,2,3,4,6,8,9-heptachlorodibenzofuran were found in seven of
      the workers. Such isomers--that is, not 2,3,7,8-substituted--are rarely found in
      human samples. CONCLUSION: Due to the long biological half lives and lipid
      solubility of PCDDs and PCDFs, blood analyses may serve as an index of past
      cumulative occupational exposure and a means of assessing a person's exposure
      situation.

PMID- 8563847
TI  - Geltape method for measurement of work related surface contamination with cobalt
      containing dust: correlation between surface contamination and airborne exposure.
AB  - OBJECTIVES: The geltape method is a new method for optical measurement of total
      amount of dust on surfaces. The objectives were to study the potential
      applicability of this method to measurements of work related cobalt exposure
      during painting of plates with cobalt dye. METHODS: Consecutive series of work
      related geltape prints were taken from surfaces inside and outside the
      ventilation cabins of two plate painters during two full working days. The amount
      of dust picked up by the geltapes was measured optically with a field monitor.
      Also, personal air samples were collected on filters at the different work
      processes. In the laboratory the contents of cobalt on the geltape prints and the
      filters were measured with inductive coupled plasma atomic emission spectroscopy.
      RESULTS: The key results were: (a) when the geltape prints were taken from
      surfaces inside the cabins the optically measured area of the geltapes covered
      with total dust (area (%)) correlated well with the chemically measured amount of
      cobalt present on the geltapes. Linear correlation coefficient (R2) was 0.91 for
      geltape prints taken on the floor and 0.94 for prints taken on the ceiling; (b)
      the cumulative airborne cobalt exposure, calculated from data on work related
      exposure by personal sampling, correlated with the area (%) of geltape prints
      taken from the ceiling of the cabin (R2 = 0.98); (c) the geltape method could be
      used to distinguish both between work processes with different levels of cobalt
      exposure, and between plate painters subjected to significant differences in
      airborne cobalt exposure. CONCLUSION: The geltape method could produce measures
      of the work related exposures as well as whole day exposure for cobalt. The
      geltape results correlated with measurements of personal airborne cobalt
      exposure. In this industry the profile of exposure is well-defined in time, and
      it seems reasonable to apply this fast and low cost method in routine exposure
      surveillance to obtain a more detailed description of the exposure than can be
      obtained by the use of airborne measurements only.

PMID- 8563850
TI  - Dimercaptosuccinic acid (DMSA): negligible effect on manganese in urine and
      blood.

PMID- 8563848
TI  - Acute effects of vibration on digital circulatory function in healthy men.
AB  - OBJECTIVES: To investigate the local and central pathophysiological mechanisms
      involved in the acute effects of unilateral vibration on the digital circulation
      of healthy men. METHODS: Finger blood flow (FBF) and finger skin temperature
      (FST) in thermoneutral conditions, and the percentage change in finger systolic
      pressure (FSP%) after local cooling from 30 to 10 degrees C were measured in the
      fingers of both hands in eight men (aged 23-47 years) who were not occupationally
      exposed to hand transmitted vibration. The right hand was exposed for 30 minutes
      to sinusoidal vibration with a frequency of 125 Hz and an acceleration of 87.5
      m.s-2 rms (root mean square). A control condition consisted of exposure to static
      load only (10 N) without vibration. The measures of digital circulation were
      taken before exposure to vibration and static load and at 0, 30, 60, and 90
      minutes after the end of each exposure. RESULTS: Exposure to static load caused
      no significant changes in FBF, FST, or FSP% in either the test right or the
      control left finger. Immediately after vibration exposure, there was a temporary
      increase in FBF in the vibrated right finger, whereas the non-vibrated left
      finger showed no vasodilation. In both the vibrated and non-vibrated fingers, FBF
      and FST were significantly reduced during the recovery time. A large variability
      between subjects was found for FBF and, to a lesser extent, for FST. In the
      vibrated right hand the decrease in FBF was significantly related to cold induced
      vaso-constriction in the digital vessels. Such a relation was not found in the
      non-vibrated left hand. CONCLUSIONS: The results of this investigation suggest
      that acute vibration can disturb the function of digital vessels through two
      different and opposite mechanisms. Vibration seems to produce local vasodilation
      and to trigger a central sympathetic reflex vasoconstriction that can be recorded
      in the ipsilateral and the contralateral finger to vibration. Both local and
      central vasoconstrictor mechanisms are likely to be involved in the
      responsiveness to cold found in the digital vessels of a vibrated finger.

PMID- 8563849
TI  - Some altered concentrations of elements in semen of workers exposed to
      trinitrotoluene.
AB  - OBJECTIVES: A cross sectional study was performed to find the concentrations of
      elements contained in the semen of workers exposed to trinitrotoluene (TNT).
      SUBJECTS AND METHODS: Semen of exposed workers in two TNT plants located in He
      Nan Province in 1992 were examined. RESULTS: The average TNT concentrations in
      the workplace, except the packing site, were found to have exceeded the maximal
      allowable concentration (MAC, 1 mg/m3); skin contaminations of male workers
      exposed to TNT were higher after a shift than in controls, and correlated with
      the total blood concentrations of TNT, 4-amino-2, 6-dinitrotoluene (4A), and 2
      amino-4, 6-dinitrotoluene (2A). Cu, Zn, Na, Mg, and Se concentrations were
      significantly decreased, but K, Ca, Co, Mn and Li contents were not significantly
      changed in the semen of workers exposed to TNT. Compared with the control group,
      the percentage of liquifying time of semen, the sperm malformation incidence, and
      viability in the men exposed to TNT were all significantly changed. CONCLUSIONS:
      Men exposed to TNT have decreased concentrations of some elements is semen and
      altered semen physiology.

PMID- 8563851
TI  - Cancer in relation to occupational exposure to trichloroethylene.

PMID- 8563852
TI  - Mortality of white South African gold miners.
AB  - OBJECTIVES: This two part study aimed to determine whether there was an excess
      mortality generally or for some diseases among middle aged white South African
      gold miners on the Witwatersrand and whether the underground dust exposure of
      these miners contributed to the development of lung cancer, chronic obstructive
      pulmonary disease (COPD), or ischaemic heart disease (IHD). METHODS: A cohort of
      4925 white miners in South Africa, born between 1 January 1916 and 31 December
      1930 who were alive and working in the vicinity of Johannesburg on 1 January
      1970, then aged between 39 and 54, was followed up for 20 years by which time
      2032 had died. Most were gold miners (about 87% had worked 85% or more of their
      shifts in gold mines). Standardised mortality ratios (SMRs) were calculated as
      percentages of the number of deaths observed in the cohort for a condition as
      stated on the death certificate divided by the number expected on the basis of
      concurrent mortality in the reference population (the total age specific white
      male population of South Africa). A case-control analysis was performed for three
      diseases (lung cancer, COPD, and IHD), the results of which are presented for
      those miners in the cohort who had spent at least 85% of their service on gold
      mines and had worked at least 15% of their shifts underground. RESULTS: The SMR
      for all causes of death was 129.6%, raised because of excess mortality due to the
      following causes: lung cancer (SMR = 139.8%), IHD (124.1%), COPD (189%) and
      cirrhosis of the liver (155.3%). Smoking was confirmed to be the main risk factor
      for lung cancer and COPD although cumulative dust exposure was found to increase
      the risk of COPD in conjunction with smoking. No significant risk of lung cancer
      resulted from exposure to dust. High blood pressure and smoking were found to
      increase the risk of IHD, but no association between IHD and the quetelet index
      (weight/height2) was found. CONCLUSIONS: The most significant and unexpected
      finding was the 30% increase in the SMR for all causes. Very little of this
      increase could be attributed to mining and the main factor for this was probably
      the adoption of an unhealthy lifestyle by these men (compared with other South
      African white men) particularly smoking (86% were smokers) and alcohol
      consumption.

PMID- 8563853
TI  - A case cohort study of suicide in relation to exposure to electric and magnetic
      fields among electrical utility workers.
AB  - OBJECTIVES: This case cohort study examines whether there is an association
      between exposure to electric and magnetic fields and suicide in a population of
      21,744 male electrical utility workers from the Canadian Province of Quebec.
      METHODS: 49 deaths from suicide were identified between 1970 and 1988 and a
      subcohort was selected comprising a 1% random sample from this cohort as a basis
      for risk estimation. Cumulative and current exposures to electric fields,
      magnetic fields, and pulsed electromagnetic fields (as recorded by the POSITRON
      meter) were estimated for the subcohort and cases through a job exposure matrix.
      Two versions of each of these six indices were calculated, one based on the
      arithmetic mean (AM), and one on the geometric mean (GM) of field strengths.
      RESULTS: For cumulative exposure, rate ratios (RR) for all three fields showed
      mostly small non-significant increases in the medium and high exposure groups.
      The most increased risk was found in the medium exposure group for the GM of the
      electric field (RR = 2.76, 95% CI 1.15-6.62). The results did not differ after
      adjustment for socioeconomic state, alcohol use, marital state, and mental
      disorders. There was a little evidence for an association of risk with exposure
      immediately before the suicide. CONCLUSION: Some evidence for an association
      between suicide and cumulative exposure to the GM of the electric fields was
      found. This specific index was not initially identified as the most relevant
      index, but rather emerged afterwards as showing the most positive association
      with suicide among the 10 indices studied. Thus the evidence from this study for
      a causal association between exposure to electric fields and suicide is weak.
      Small sample size (deaths from suicide) and inability to control for all
      potential confounding factors were the main limitations of this study.

PMID- 8563854
TI  - A mortality study of electrical utility workers in Quebec.
AB  - OBJECTIVES: The objective of this study was to investigate the mortality of
      electrical utility workers exposed to electric and magnetic fields. METHODS: A
      historical cohort mortality study was carried out on 21,744 workers who were
      employed in an electrical company in the province of Quebec between 1970 and
      1988. The last job held by each study subject was coded. A job exposure matrix
      (JEM) was used to estimate the exposure to 60 Hz electric and magnetic fields,
      and pulsed electromagnetic fields (as recorded by the PEMF (POSITRON) meter) in
      this job. Standardised mortality ratios (SMRs) were calculated relative to Quebec
      men. Because the exposure was exclusively among blue collar workers, the
      remainder of the analyses by exposure were restricted to them. Rate ratios (RRs)
      in the exposed groups relative to the background groups were estimated with
      Poisson regression. There were 1582 deaths by the end of follow up. RESULTS: SMRs
      were almost all below one and never substantially increased, although there were
      a few increased rate ratios (RRs). There was a significant RR of 2.00 (95%
      confidence interval (95% CI) 1.37-2.93) for deaths caused by accidents and
      violence in workers exposed to magnetic fields, RR of 1.82 (95% CI 1.25-2.65) for
      electric fields, and RR of 1.62 (95% CI 1.13-2.32) for pulsed electromagnetic
      fields. Occupational accidents related to power lines explain some of the excess
      of deaths from accidents and violence. Some association was found between
      magnetic fields and leukaemia, brain cancer, and suicide, between electric fields
      and brain cancer and suicide, and between pulsed electromagnetic fields and lung
      cancer, but these were not significant. CONCLUSION: These results are broadly
      reassuring that major causes of death are not strongly associated with exposure
      to electric and magnetic fields, but small numbers and approximate exposure
      assessments preclude the denial of any risk, in particular if it were to affect a
      rare cause of death.

PMID- 8563855
TI  - Effects on the nervous system among welders exposed to aluminium and manganese.
AB  - OBJECTIVES: The purpose was to study the effects on the nervous system in welders
      exposed to aluminium and manganese. METHODS: The investigation included
      questionnaires on symptoms, psychological methods (simple reaction time, finger
      tapping speed and endurance, digit span, vocabulary, tracking, symbol digit,
      cylinders, olfactory threshold, Luria-Nebraska motor scale), neurophysiological
      methods (electroencephalography, event related auditory evoked potential (P-300),
      brainstem auditory evoked potential, and diadochokinesometry) and assessments of
      blood and urine concentrations of metals (aluminium, lead, and manganese).
      RESULTS: The welders exposed to aluminium (n = 38) reported more symptoms from
      the central nervous system than the control group (n = 39). They also had a
      decreased motor function in five tests. The effect was dose related in two of
      these five tests. The median exposure of aluminium welders was 7065 hours and
      they had about seven times higher concentrations of aluminium in urine than the
      controls. The welders exposed to manganese (n = 12) had a decreased motor
      function in five tests. An increased latency of event related auditory evoked
      potential was also found in this group. The median manganese exposure was 270
      hours. These welders did not have higher concentrations of manganese in blood
      than the controls. CONCLUSIONS: The neurotoxic effects found in the groups of
      welders exposed to aluminium and manganese are probably caused by the aluminium
      and manganese exposure, respectively. These effects indicate a need for
      improvements in the work environments of these welders.

PMID- 8563856
TI  - Blood antioxidant enzymes as markers of exposure or effect in coal miners.
AB  - OBJECTIVE: To investigate if blood Cu++/Zn++ superoxide dismutase, glutathione
      peroxidase, catalase, and total plasma antioxidant activities could be markers of
      biological activity resulting from exposure to respirable coal mine dust in
      active miners, and of pneumoconiosis in retired miners. METHODS: Blood samples
      were randomly obtained from active surface workers (n = 30) and underground
      miners (n = 34), and from retired miners without (n = 21), and with (n = 33)
      pneumoconiosis. Antioxidant enzyme activities and total plasma antioxidants were
      measured in erythrocytes and plasma. Non-parametric tests were completed by
      analyses of covariance to compare antioxidants between groups, taking into
      account potential confounding factors (age, smoking history (pack-years)).
      RESULTS: Erythrocyte Cu++/Zn++ superoxide dismutase activity was significantly
      higher in the group of underground miners than the group of surface workers. The
      differences in total plasma antioxidants and plasma glutathione peroxidase
      activity between both groups were related to age. Glutathione peroxidase activity
      increased in the plasma of retired miners with pneumoconiosis, compared with
      retired miners without pneumoconiosis. No differences were found either in
      erythrocyte antioxidant enzyme activities or in total plasma antioxidants between
      the groups of retired miners without and with pneumoconiosis. CONCLUSIONS: In
      this study, erythrocyte Cu++/Zn++ superoxide dismutase activity may be considered
      as a marker of effect of respirable coal mine dust in exposed workers. This
      result is in agreement with the hypothesis that reactive oxygen species are
      involved in cell injury induced by coal mine dust, and may be predictive of the
      degree of inflammation and pneumoconiosis induced by coal mine dust. The increase
      in glutathione peroxidase activity in the plasma of retired miners with
      pneumoconiosis may be the result of a response to the increasing hydrogen
      peroxide (H2O2) production due to the disease process.

PMID- 8563858
TI  - Health complaints and working conditions experienced in relation to work and age.
AB  - OBJECTIVES: The main objective is to describe the potential health and work
      problems of the aging employees in the Dutch working population. In this way, we
      can identify groups at extra risk of specific health problems. METHODS: In The
      Netherlands, occupational health services gather questionnaire data about work
      and health as part of periodical occupational health surveys (POHSs). These data
      from the POHSs of complaints about health and working conditions, aggregated into
      occupational groups and age categories, are used to provide indications for
      groups at extra risk of specific health problems. These problems are assessed by
      overviews of the relation between age and complaints about health and working
      conditions. RESULTS: Almost all of the health questions show an increase in
      health complaints with increasing age. White collar workers, especially the high
      grade white collar workers, usually have lower complaint percentages on health
      questions than blue collar workers. Female employees have relatively high
      complaint percentages on the health questions. Differences between occupational
      groups in the complaints about work and working conditions reflect the
      differences in work demands and exposure. The relation between age and work
      complaints is generally inconsistent and weak. The complaint percentages on work
      questions of female employees tend to be equal to or lower than those of the male
      employees. CONCLUSIONS: The absence of a clear increase of work complaints with
      advancing age in the presence of a decrease in health and working capacity may be
      explained by a selective turnover in the working population, especially in
      demanding occupations. To enhance the work participation of older employees it
      may be necessary to reduce the work demands and to increase decision latitude.

PMID- 8563857
TI  - Lung function in Lancashire cotton and man made fibre spinning mill operatives.
AB  - OBJECTIVES: This survey was conducted to investigate current lung function levels
      in operatives working with cotton and man made fibres. Dust concentrations,
      smoking history, and occupational details were recorded so that factors
      influencing lung function could be identified. METHODS: A cross sectional study
      of respiratory symptoms and lung function was made in 1057 textile spinning
      operatives of white caucasian extraction. This represented 96.9% of the total
      available working population to be studied. Most (713) worked currently with
      cotton. The remainder worked with man made fibre. Lung function was assessed by
      measuring forced expiratory volume in one second (FEV1) and forced vital capacity
      (FVC). Exposure to cotton dust was measured in the work area and personal
      breathing zones, and retrospective exposure to cotton dust over a working life
      was estimated with accurate work history and best available hygiene data.
      RESULTS: 3.5% of all operatives had byssinosis, 55 (5.3%) chronic bronchitis, 36
      (3.5%) work related persistent cough, 55 (5.3%) non-byssinotic work related chest
      tightness, and 56 (5.3%) work related wheeze. A total of 212 static work area
      dust samples (range 0.04-3.23 mg/m3) and 213 personal breathing zone samples
      (range 0.14-24.95 mg/m3) were collected. Percentage of predicted FEV1 was reduced
      in current smokers (mean 89.5, 95% confidence interval (95% CI) 88-91) in
      comparison with non-smokers (93.1, 90.5-94.1) and FVC was reduced in operatives
      currently working with man made fibre (95.3, 93.8-96.9) in comparison with cotton
      (97.8, 96.6-99.0). Regression analysis identified smoking (P < 0.01), increasing
      age (P < 0.01), increasing time worked in the waste room (P < 0.01), and male sex
      (P < 0.05) as being associated with a lower FEV1 and FVC. Current and
      retrospective cotton dust exposures did not appear as predictor variables in the
      regression analysis although in a univariate analysis, FEV1 was reduced in those
      operatives exposed to high dust concentrations assessed by personal and work area
      sampling. DISCUSSION: This study has documented loss of lung function in
      association with exposure to cotton dust. Those operatives with work related
      symptoms had significantly lower FEV1 and FVC than asymptomatic workers. Although
      lung function seemed to be affected by high dust exposures when operatives were
      stratified into high and low exposure groups, regression analysis did not
      identify current dust concentrations as an independent factor influencing loss.
      Smoking habit was found to explain most of the measured change in FEV1 and FVC.
      It is likely that smoking and dust exposure interact to cause loss of lung
      function in cotton textile workers.

PMID- 8563859
TI  - Reliability of a questionnaire on sickness absence with specific attention to
      absence due to back pain and respiratory complaints.
AB  - OBJECTIVE: To evaluate the performance of a questionnaire on sickness absence due
      to back pain and respiratory disorders with the view of using sickness absence as
      a measure of morbidity. METHODS: A cross sectional survey was conducted among 511
      male workers aged 20-65, drawn from the personnel register of an animal feed
      mill. The response was 404 (79%) participants. Data on sickness absence in the
      six months before the survey were collected by a self administered questionnaire
      and by sickness absence records. Correlation between both methods was examined
      for prevalence, duration, and frequency of overall sickness absence, back pain
      absence, and absence due to respiratory complaints. RESULTS: The questions about
      the prevalence of sickness absence from all causes, back pain, and respiratory
      complaints showed a high specificity of 91%, 97%, and 98%, respectively. The
      sensitivities of these questions were 79%, 88%, and 13%, respectively. The survey
      found a moderate agreement between the questionnaire and the medical register for
      duration and frequency of overall sickness absence with kappa values of 0.54 and
      0.50. A good agreement was found for back pain absence with kappa values of 0.65
      and 0.61. Respiratory absence showed a poor agreement of 0.16 and 0.13.
      CONCLUSION: In epidemiological studies questionnaires might be considered a
      valuable source of information on overall sickness absence or absence due to back
      pain which lasted for at least two weeks in the past six months. Whether a
      questionnaire survey is a reliable source of data on sickness absence due to
      respiratory complaints remains to be seen.

PMID- 8563860
TI  - Bladder cancer and occupation: a case-control study in northern Italy.
AB  - OBJECTIVES: A hospital based case-control study was conducted between 1992 and
      1993 in the province of Brescia, a highly industrialised area in northern Italy,
      to evaluate occupational risk factors of bladder cancer. METHODS: The study
      evaluated 355 histologically confirmed cases of bladder cancer (275 men, 80
      women) and 579 controls affected by urological non-neoplastic diseases (397 men,
      182 women). Lifetime occupational history, smoking and drinking habits, and
      sociodemographic characteristics were recorded by means of a structured
      questionnaire. Odds ratios (ORs) were computed with adjustment for age, smoking,
      alcohol and coffee consumption, education, and place of residence. RESULTS: A
      significant (P < 0.05) increase of risk of bladder cancer were found in men for
      labourers in the construction industry (OR 2.1, 95% confidence interval (95% CI)
      1.1-3.9) and for recreational and cultural services (OR 5.0, 95% CI 1.3-18.9).
      Increased risks, although not significant, were found for various other
      occupations and industries such as machinery mechanics, metal processers and
      polishers, blacksmiths, gunsmiths, painters; for transport workers, an increased
      risk with increasing duration of employment was found. CONCLUSIONS: Occupational
      exposures seem to contribute to bladder cancer risk in the area under study.

PMID- 8563861
TI  - Enzyme immunoassays for total and allergen specific IgE in population studies.
AB  - OBJECTIVE: Extensive IgE serology in occupational or environmental health studies
      is often hampered by a lack of technical facilities and finance. The use in
      population studies of relatively simple and inexpensive enzyme immunoassays
      (EIAs) was therefore evaluated for the assessment of total serum immunoglobulin E
      (IgE), and of specific IgE reactions with various common (house dust mites, grass
      and birch pollen, and cat) or occupational (fungal alpha-amylase and rat urinary
      protein) allergens. METHODS: Total IgE was measured with a sandwich EIA,
      calibrated with commercially available IgE standards. Reproducibility was studied
      by testing pooled normal human serum samples in each of a large series of test
      plates. A panel of 156 children's serum samples with known IgE values was used to
      compare the assay with other total IgE assays. A previously developed EIA for
      anti-yeast IgE was adapted for the measurement of IgE reacting with various
      common and occupational allergens. Binding of IgE to microwells coated with
      commercially available allergen extracts, or allergen preparations from our own
      laboratory, was measured with a monoclonal anti-human IgE antibody and subsequent
      incubations with biotinylated rabbit anti-mouse Ig and avidin-peroxidase. Panels
      of serum samples from school children (n = 116), bakery workers (n = 126), and
      laboratory animal workers (n = 52) were used to study sensitivity and
      specificity, with reference to skin prick tests as the standard, and to compare
      the EIAs with commercially available test kits. RESULTS: The detection limit of
      the EIA for total IgE was 0.5-1 kU/l for undiluted serum samples, and the
      coefficient of variation between assays was less than 15% at serum concentrations
      between 1 and 150 kU/l. Results obtained with the panel of 156 children's serum
      samples were strongly correlated (r2 = 0.86) with IgE concentrations measured
      previously by radioimmunoassay. The results of the EIA for various occupational
      allergens correlated very well, both qualitatively and quantitatively, with the
      results of commercial test kits. Sensitivity and specificity of the EIA results
      as a predictor of skin prick test reactivity towards common allergens (house dust
      mite, grass pollen, birch pollen, and cat) were remarkably high (> 80%-90%) in
      the series of 116 children's serum samples. In a population of bakery workers the
      specificity of the EIAs was also very high (> 90%). The sensitivity was notably
      lower (30%-70%) in this adult population, which is, however, in agreement with
      results reported for conventional IgE tests. CONCLUSION: As the costs were
      estimated to be at least five to 10-fold lower than those of commercial test
      kits, the EIAs for total and specific IgE may be very useful tools in
      epidemiological studies of atopic respiratory or other disorders.

PMID- 8563862
TI  - Gall bladder cancer cluster in a food industry.

PMID- 8563863
TI  - Need for vaccination of sewer workers against leptospirosis and hepatitis A.

PMID- 8563865
TI  - International Symposium on Recent Advances in Inflammatory Bowel Disease. Nara,
      Japan, November 23-24, 1994.

PMID- 8563864
TI  - Occupational medicine: the way ahead.

PMID- 8563866
TI  - Incidence and prevalence of inflammatory bowel disease in Japan: nationwide
      epidemiological survey during the year 1991.
AB  - The aim of this nationwide study was to determine the recent incidence and
      prevalence of inflammatory bowel disease, i.e., Crohn's disease (CD) and
      ulcerative colitis (UC), in Japan. We mailed out a preliminary examination sheet
      with diagnostic criteria, asking about the presence of patients with inflammatory
      bowel disease, to all hospitals in Japan that have more than 200 beds for general
      use. The rate of reply was 60.93%. A total of 4243 patients with CD were
      reported. The incidence per 100 000 population per annum was 0.51 (0.71 in males,
      0.32 in females). The prevalence per 100 000 population per annum was 5.85 (7.94
      in males, 3.83 in females). Peak age at onset was 20-24 years in males and 15-19
      years in females. A total of 12559 cases of UC were reported. The incidence per
      100 000 population per annum was 1.95 (2.23 in males, 1.68 in females). The
      prevalence per 100 000 population per annum was 18.12 (18.70 in males, 18.17 in
      females). Peak age at onset was 20-24 years in males and 25-29 years in females.

PMID- 8563867
TI  - Nutritional support in Crohn's disease: current status and future directions.

PMID- 8563868
TI  - Double-blind comparative study of sulfasalazine and controlled-release mesalazine
      tablets in the treatment of active ulcerative colitis.
AB  - To evaluate the effect of a controlled-release mesalazine tablet, in patients
      with ulcerative colitis (UC), a multicenter double-blind study was carried out,
      using sulfasalazine (500 mg tablet) as the control drug. The mesalazine tablet
      contained 250 mg of ethyl cellulose-coated mesalazine granules. The patients were
      assigned to two groups, one to receive mesalazine tablets (1500 mg/day) and a
      sulfasalazine placebo (group M) and the other to receive sulfasalazine tablets
      (3000 mg/day) and a mesalazine placebo (group S). The test medications were
      administered orally for 4 consecutive weeks. The study subjects were selected
      from among patients with mild to moderate active UC, and 118 patients were
      enrolled. Concomitant use of steroids and immunosuppressors was prohibited during
      the study period. Of the 118 patients, 9 dropped out. A total of 109 complete
      records were thus obtained, 52 in group M and 57 in group S. There was no
      difference in the improvement of clinical symptoms and endoscopic findings
      between the two groups. The overall safety, based on adverse reactions and
      laboratory data, was higher, at 86.5%, for group M (n = 52), compared to 66.7%
      for group S (n = 57). The general usefulness, based on the improvement and
      safety, was higher, at 65.3%, for group M (n = 49), compared to 45.6% for group S
      (n = 57). The controlled-release mesalazine tablet thus appears to be useful in
      the treatment of mild to moderate active UC.

PMID- 8563869
TI  - Bioavailability of controlled release mesalazine (5-ASA) preparations.
AB  - Salazosulfapyridine was generated by Nanna Svartz in 1941. Mesalazine (5-ASA) was
      demonstrated in 1977 to be the therapeutically active moiety of
      salazosulfapyridine. Since then, a number of alternatives to salazosulfapyridine
      have appeared: olsalazine and salicylazobensoic acid, which are as
      salazosulfapyridine azo-preparations. Also, pure mesalazine drugs have been
      developed: Asacol, Claversal, and Pentasa. Despite the many similarities of these
      pure mesalazine controlled-release drugs, there are also significant differences.
      Some of these are due to different pharmaceutical designs of the delivery
      principle. Other important parameters are gastrointestinal pH variations in the
      healthy and diseased gut, and variations in ventricular emptying and in
      intestinal transit patterns.

PMID- 8563870
TI  - Adverse effects of sulfasalazine and treatment of ulcerative colitis with
      mesalazine.
AB  - We investigated the adverse effects of sulfasalazine in the treatment of
      inflammatory bowel disease in Japan. In our first survey, adverse effects were
      observed in 52 out of 751 patients with ulcerative colitis (6.9%) and in 8 out of
      221 patients with Crohn's disease (3.6%); i.e., such effects were observed in 60
      out of 972 patients with inflammatory bowel disease. In our second survey, we
      examined 94 adverse reactions in 64 patients with ulcerative colitis. The main
      adverse reactions were exanthema, fever, nausea and vomiting, angioedema, and
      liver damage, in decreasing order of frequency; these reactions accounted for
      about 80% of the adverse reactions. Most of the reactions (62%) occurred within 1
      month after the beginning of sulfasalazine intake. Mesalazine is thought to
      effectively release the 5-ASA molecule in the colon and has already proven of
      value in patients with mild active ulcerative colitis. We evaluated the effect of
      mesalazine in patients intolerant to sulfasalazine. Effectiveness was observed in
      14 out of 18 patients with active ulcerative colitis (78%) and in 3 out of 3
      patients in the quiescent state. These results suggest that mesalazine is
      effective for the treatment of patients with ulcerative colitis who are
      intolerant to sulfasalazine; this drug could be a gleam of hope to those
      patients.

PMID- 8563871
TI  - Corticosteroids for the management of ulcerative colitis.
AB  - Two studies were carried out. In the first, 24 patients with severe ulcerative
      colitis (UC) were prospectively studied by the Research Group of Inflammatory
      Bowel Disease, sponsored by the Ministry of Health and Welfare of Japan. Patients
      were randomly assigned to two groups; one group (n = 13) was given prednisolone,
      1.0 mg/kg body weight, daily, the other group (n = 11) was given prednisolone,
      1.5 mg/kg body weight, daily. The 13 patients given 1.0 mg/kg prednisolone
      consisted of 7 with left-sided colitis and 6 with total colitis; 11 patients
      given 1.5 mg/kg prednisolone consisted of 5 with left-sided and 6 with total
      colitis. There were no statistically significant differences in clinical,
      endoscopic, and overall improvement between the two groups; however, 1.5 mg/kg
      prednisolone was significantly more effective in the treatment of the patients
      exhibiting the first attack. In the second study, 6 patients with severe and 7
      with moderately severe UC were given megadose pulsed steroid therapy. Five
      hundred or 1000 mg of either hydrocortisone-21-sodium succinate or
      methylprednisolone was given once a day intravenously. Ten patients achieved
      clinical remission, 1 patient improved, and 2 patients did not respond.
      Endoscopically, 5 patients achieved remission, 6 patients improved, and 2 did not
      respond. Adverse effects severe enough to stop the medication were not noted.
      Steroid withdrawal syndrome also was not noted.

PMID- 8563872
TI  - Immunosuppressive agents in the treatment of Crohn's disease and ulcerative
      colitis.
AB  - Low doses of 6-mercaptopurine (6MP) were used for the treatment of inflammatory
      bowel disease, and 20-30 mg/day was found to be effective for patients with
      ulcerative colitis who were corticosteroid-dependent or corticosteroid-resistant.
      Corticosteroid was tapered in 20 of 21 patients with ulcerative colitis. Of 15
      patients who were refractory to conventional therapy, 11 responded to 6MP
      treatment. The same doses of 6MP were given to patients with Crohn's disease who
      were corticosteroid-dependent or who had associated fistula. Treatment with 6MP
      did not influence the changes in colonic or ileac lesions in Crohn's disease.
      However, the fistulas were closed or improved in 70% of 10 patients by 6MP
      treatment. The adverse effects of small doses of 6MP were minimal. These results
      confirm that immunosuppressive agents are effective for patients with
      inflammatory bowel disease. In a rat colitis model induced by immunization with
      trinitrobenzene (TNB), we used anti-CD4 monoclonal antibodies to prevent colonic
      inflammation; these antibodies were effective for this colitis model, suggesting
      that a novel therapy targeting CD4 intestinal lymphocytes may be feasible in the
      treatment of Crohn's disease.

PMID- 8563873
TI  - Leukocytapheresis therapy with leukocyte removal filter for inflammatory bowel
      disease.
AB  - Leukocytapheresis (LCAP) with a leukocyte removal filter was administered to 44
      patients with inflammatory bowel disease (IBD), diagnosed as ulcerative colitis
      (UC) in 25 and Crohn's disease (CD) in 19. Clinical and blood examinations showed
      no side effects in any of the patients. During intensive therapy, clinical
      improvement was recognized in 21 of the 25 UC patients (84%), 8 of whom had an
      excellent response, and in 16 of the 19 CD patients (84.2%), 4 of whom had an
      excellent response. The clinical improvement continued throughout the maintenance
      therapy in 19 of the UC patients (76%) and in 12 of the CD patients (63.2%). In
      both the UC and the CD patients, flow cytometry study showed that those who had
      improved generally had high values for the percentages of HLADR+, HLADR+CD3+,
      HLADR+CD8+, and CD11a+CD8+ cells before the first LCAP, and that these values
      decreased to near the normal range after both intensive and maintenance therapy.
      In the patients who showed poor response, in contrast, the values had been at or
      near normal before the initial LCAP administration. The clinical improvement and
      the findings on flow cytometry suggest that LCAP exerts an immuno-modulatory
      effect and is an effective therapy for patients with IBD in whom conventional
      drug treatments have failed.

PMID- 8563874
TI  - Ileoanal anastomosis and ileoanal canal anastomosis in Japan: comparative
      retrospective study.
AB  - A questionnaire survey of ten institutions in Japan revealed that restorative
      proctocolectomy accounted for 81.8% of the surgical procedures performed in
      patients with UC in the last 5 years (1989-1993); ileoanal anastomosis (IAA) and
      ileo-anal canal anastomosis (IACA) were performed in 63% and 33% of these
      patients, respectively. Comparison of the two series showed that IACA was
      technically simpler and yielded better continence, but that it entailed a
      potential risk of recurrence of the disease in the remaining anal canal mucosa.
      Although IACA seems to be a useful surgical option for UC, until the long-term
      outcome of the procedure can be elucidated. It may be better regarded as a very
      low variation of IRA rather than as an improved technical version of IAA.

PMID- 8563875
TI  - Long-term follow-up study of ulcerative colitis in Japan.
AB  - To clarify the long-term prognosis of Japanese patients with ulcerative colitis,
      we investigated the cumulative colectomy rate and the survival rate, and compared
      the results with reports from Western countries. The subjects were 778 patients
      who had visited 8 hospitals from 1973 to 1990. A total of 114 of the 778 patients
      (14.7%) had required colectomy and 21 (2.7%) had died. These rates were higher in
      the patients who had total colitis, and in those who had acute fulminant type of
      severe type. There were no significant differences in these rates according to
      age of onset (under 29 years, 30-49 years, and more than 50 years). The
      cumulative colectomy rate increased rapidly within 2 years after onset.
      Thereafter, the rate increased gradually, by 1%-2% per year. In patients with
      total colitis, 14.1% required colectomy within 2 years. The age at onset had no
      effect on this rate. The cumulative survival rate decreased gradually throughout
      the first 10 years, the rate being 96.2% in the 10th year. No deaths occurred in
      the 11-18th years after onset. Despite our inclusion of more patients with total
      or severe colitis, our results were similar to or slightly superior to those
      reported from Western countries; this may be attributed to a temporal bias.

PMID- 8563877
TI  - Strictureplasty for Crohn's disease in Japan.
AB  - Strictureplasty has recently been advocated in the treatment of obstructive
      strictures of the small bowel in patients with Crohn's disease. In this group
      study, results for 69 patients with Crohn's disease who underwent strictureplasty
      were analyzed by sending questionnaires to 13 institutions belonging to the
      Research Committee of Inflammatory Bowel Disease of the Japanese Ministry of
      Health and Welfare. No mortality and anastomotic leakage were observed.
      Strictureplasties of both the Heineke-Mikulicz and Finney varieties were
      considered to be safe procedures, even though the sutures had to be applied at
      the slightly inflammed site. The median follow up was 37 months (range, 0-133
      months), and 12 patients needed reoperation. The cumulative 3-year operation-free
      rate was 92.5% and the 5-year rate was 70.3%. The site of the lesion, the
      strictureplasty procedure, and previous history of small bowel resection did not
      significantly influence the operation-free intervals. The cumulative 5-year
      operation-free rate of the group treated with home elemental enteral nutrition
      (83.3%) was better than that of the non-treated group (65.3%). Strictureplasty
      was found to be a safe and effective surgical procedure for high-risk patients
      with Crohn's disease in whom an appropriate length of bowel should be saved.

PMID- 8563876
TI  - Total colectomy and ileorectal anastomosis in ulcerative colitis.
AB  - In an attempt to determine the best indications for the classically adopted ileo
      rectal anastomosis (IRA) and the new techniques of restorative proctocolectomy,
      namely, ileal J-pouch-anal anastomosis (IAA) ilea J-pouch-anal canal anastomosis
      (IACA), we retrospectively studied 72 surgically treated patients with ulcerative
      colitis (UC) followed in our surgical department in the period between 1963 and
      1994. Compared to these new techniques, IRA had a lower incidence of
      postoperative fecal incontinence, and was one-stepped in the majority of the
      patients. No significant difference regarding postoperative bowel function,
      operation time, volume of bleeding, hospital stay, and the need for postoperative
      prednisolone was observed. We concluded that IRA is a good procedure that is
      indicated for patients receiving high-dose prednisolone, for those who need a
      quick return to social activity, and for those with poor anal function. IACA is a
      good indication for those patients with good anal function assessed
      preoperatively, who agree to receive a multi-step operation. For those patients
      with cancer or dysplasia, IAA should be the operation of first choice.

PMID- 8563878
TI  - Strictureplasty for Crohn's disease of small intestine. Present status in Western
      countries.
AB  - The concept of a minimal operation for Crohn's disease, particularly of the small
      intestine, is based on the rationale that it is impossible to cure Crohn's
      disease by excision, since it is a panintestinal disease that can eventually
      occur in any part of the remaining intestine. The surgeon is required to treat
      only the complications and to conserve as much intestine as possible. In the case
      of stricture, excision is not necessary if the narrowing can be corrected.
      Strictureplasty is ideal for short strictures of the small intestine in quiescent
      disease. The morbidity and mortality of strictureplasties are low in. In spite of
      leaving the "burnout" disease behind, the recurrent stricture after
      strictureplasties is comparable to the recurrence after bowel resections. The
      purpose of strictureplasty is to correct the small bowel obstruction and to
      preserve the length of the small intestine. It is, however, not intended to
      replace a small bowel resection.

PMID- 8563879
TI  - Surgery for Crohn's anal fistulas.
AB  - The aim of this study was to analyze the features of Crohn's anal fistulas and to
      evaluate the efficacy of seton treatment. In 119 patients with Crohn's disease,
      the incidence of anal fistula was 56% (67/119), with no significant difference in
      the incidence among patients with ileitis, colitis, and ileocolitis.
      "Intractable" anal fistulas were found in 17% of patients with ileitis, compared
      to 64% of those with colitis (P = 0.051) and 68% of those with ileocolitis (P =
      0.014). Seton treatment, i.e., non-cutting, long-term seton drainage, was
      performed for 21 patients (5 with intersphincteric, and 16 with transsphincteric
      fistulas). In the 16-month follow up, 9 patients required redrainage for
      recurrent fistulous abscess, mainly because of progressive colorectal disease.
      Finally, a good result was obtained in 17 of the 21 patients (81%) and no
      recurrent fistulous abscess developed in the 8 patients in whom all setons were
      removed. Anal continence was preserved in all the patients. These results
      indicate that anal fistulas with Crohn's ileitis were cured more easily than
      those with colitis or ileocolitis, and that seton treatment was effective for
      intersphincteric fistula with multiple fistula openings and for transphincteric
      fistulas in patients exhibiting remission of intestinal Crohn's disease.

PMID- 8563880
TI  - Long-term follow-up study of Crohn's disease in Japan. The Research Committee of
      Inflammatory Bowel Disease in Japan.
AB  - Two hundred and three patients with Crohn's disease seen at Kyushu University,
      Fukuoka University, and their affiliated centers from 1973 to 1988 were followed
      for 4.4 +/- 3.2 years (mean +/- SD), to evaluate the prognosis relative to life
      span and surgery. Cumulative survival rate and cumulative operation rate were
      calculated by the life table method. Cumulative survival rates 5 and 10 years
      after diagnosis were 98.9% and 98.9%, respectively; these figures were not
      different from the expected survival rates in the sex-and age-matched general
      population. Cumulative operation rates 5 and 10 years after the onset of symptoms
      were 16.2% and 39.1%, respectively, In a second study, we investigated 419
      patients with Crohn's disease, diagnosed at nine institutions from 1975 to 1990.
      The follow-up period was 6.3 +/- 3.9 years and the information was obtained from
      mailed questionnaires. Cumulative survival rates 5 and 10 years after diagnosis
      were 99.2% and 96.9%, respectively. Cumulative operation rates 5 and 10 years
      after the onset of symptoms were 30.3% and 70.8%, respectively. These results
      indicate that the prognosis of Japanese patients with Crohn's disease may be
      superior to that reported in Western countries.

PMID- 8563881
TI  - Histological classification of the neoplastic changes arising in ulcerative
      colitis: a new proposal in Japan.
AB  - Patients with total ulcerative colitis with a longstanding course of the disease
      have a high risk of developing colorectal carcinoma. Colonoscopic surveillance to
      detect precancerous tissue and/or cancer in these patients has been carried out
      in countries with a high incidence of ulcerative colitis. Riddell's
      classification has been widely used for the interpretation of biopsy specimens
      obtained from the colonoscopic surveillance. In Japan, however, there are
      problems in accepting Riddell's classification, mainly because the intramucosal
      carcinomas diagnosed by Japanese histopathologists are included in the category
      of high-grade dysplasia in Riddell's classification. Based on the results of a
      meticulous slide review carried out by seven histopathologists in this study, a
      new classification is proposed: UC-I, inflammatory change; UC-II, indefinite; UC
      IIa, probably inflammatory; UC-IIb, probably neoplastic; UC-III, neoplastic but
      not carcinomatous; and UC-IV, carcinoma. Intramucosal carcinomas is included in
      the category UC-IV. We consider that the diagnosis of intramucosal carcinoma is
      to be made when there is a high grade of cytological and structural atypia
      consistent with carcinoma. Interobserver and intraobserver variability with this
      classification was acceptable. We believe this new classification will be widely
      use in cancer surveillance in ulcerative colitis in Japan.

PMID- 8563882
TI  - Implications of a diagnosis of dysplasia in ulcerative colitis.

PMID- 8563883
TI  - Detection of c-ras gene mutation and expression of p21 protein in dysplasias and
      carcinomas complicating ulcerative colitis.
AB  - Point mutations of c-ras genes and the expression of p21 protein were analyzed in
      13 patients with colorectal carcinoma complicating ulcerative colitis; in 12 of
      the 13, there were dysplastic lesions close to the carcinomas. Point mutations of
      c-ras genes were studied by polymerase chain reaction and dot blot hybridization
      with 32p-labeled oligonucleotide probes. Findings indicated mutations of c-Ki-ras
      at condons 12, 13, and 61 and c-Ha-ras and c-N-ras at condons 12 and 61. The
      expression of p21 protein was analyzed by immunohistochemical staining using a
      monoclonal antibody. Only 1 of the 13 patients with carcinoma showed a point
      mutation, this being from G to A transition at the second position of codon 12 of
      c-Ki-ras. No point mutations of c-Ki-ras, c-Ha-ras, or c-N-ras were found in
      other carcinomatous lesions and dysplasias. In the dysplastic or carcinomatous
      lesions of 11 patients, the increased expression of p21 protein was observed.
      These results suggest that point mutations of c-ras genes are rare in dysplasias
      and carcinomas complicating ulcerative colitis and that the increased expression
      of p21 protein is not always correlated with point mutations of c-ras genes.

PMID- 8563884
TI  - Over-expression of p53 protein in neoplastic changes in ulcerative colitis:
      immunohistochemical study.
AB  - An immunohistochemical study using PAb1801, a monoclonal antibody specific to the
      human p53 protein (wild and mutant), was performed to detect over-expression of
      p53 protein in colorectal cancers and dysplasia complicating ulcerative colitis,
      compared with that in sporadic colorectal cancers and adenomas. The over
      expression of p53 was demonstrated in 6/7 (85.7%) cancers and in 15/18 (75.0%)
      dysplasias complicating ulcerative colitis. The frequency of p53 over-expression
      was 126/200 (63.0%) in sporadic cancers and 4/120 (3.3%) in adenomas. This study
      suggests that alteration of the p53 gene is implicated in the development of
      cancers complicating ulcerative colitis, as it is in the development of sporadic
      colorectal cancers, and it appears to be involved at a relatively early stage.

PMID- 8563885
TI  - Colonoscopic diagnosis of dysplasia and early cancer in longstanding colitis.
AB  - Five colitic cancers were detected among 40 patients with longstanding total
      colitis. The colitic cancers did not show the common polypoid or ulcerated
      appearance in the early stage, often being flat or plaque-like. It was not easy
      to detect these lesions endoscopically, and it was often impossible to do so
      radiologically. The flat or plaque-like early cancers were often surrounded by
      granular and/or red mucosa. We believed that the colonoscopic detection of this
      colitic cancer and dysplasia was difficult because: (1) the morphology of the
      lesions was difficult to determine, (2) the background mucosa was not normal.
      When the lesions were small, it was more difficult to detect them on the colitic
      mucosa than on the normal mucosa. The contrast between the lesion and the
      background mucosa was not clear in the latter condition. In surveillance
      colonoscopy (using a TV colonoscope) for longstanding ulcerative colitis, careful
      scrutiny throughout the large intestine is required to detect colitic cancers and
      dysplasia at an early state.

PMID- 8563886
TI  - Results of cancer surveillance in ulcerative colitis.
AB  - A total of 144 patients with total or left-sided colitis of 7 years or more
      duration were enrolled in a surveillance program to screen for dysplasia at Tokyo
      University Hospital between 1979 and 1994. The program consisted of an annual
      colonoscopy, with multiple biopsies being performed at 10-cm intervals in the
      colonic flat mucosa; additional biopsies were taken from elevated lesions. A
      higher proportion of patients who had had four surveillance colonoscopies or more
      up to the detection of carcinoma had an earlier stage of carcinoma compared with
      patients who had had less than three colonoscopies. In addition, the incidence
      and stage of carcinoma were higher in the patients with an initially higher grade
      of dysplasia and in those patients with elevated lesions compared with patients
      with flat mucosal lesions with the same grade of dysplasia.
      Microspectrophotometric DNA analysis was performed for 66 consecutive patients
      who had been under surveillance between 1987 and 1990. Dysplasia and carcinoma
      occurred at a higher rate in patients who had an initial abnormal DNA content
      compared with patients who showed diploidy. These findings indicate that
      surveillance colonoscopy with DNA analysis could be useful in the early detection
      of colonic carcinoma in long-standing ulcerative colitis.

PMID- 8563887
TI  - Requirements of a cancer screening program to be scientifically credible.

PMID- 8563888
TI  - The pathogenic role of Bacteroides vulgatus in patients with ulcerative colitis.
AB  - To clarify the role played by Bacteroides vulgatus in the pathogenesis of
      ulcerative colitis, the serum antibody titer to the outer membrane protein of B.
      vulgatus, obtained from the inflamed rectal mucosa, and measured by enzyme-linked
      immunosorbent assay, was investigated in patients with ulcerative colitis. High
      serum antibody titers to the outer membrane protein of B. vulgatus were found in
      these patients. The specific outer membrane protein of B. vulgatus reactive to
      serum antibody was recognized as a 26-kDa protein. These findings indicate that
      B. vulgatus containing a 26-kDa protein in the outer membrane may be implicated
      in the pathogenesis of ulcerative colitis.

PMID- 8563889
TI  - Measles virus and Crohn's disease: research from the Royal Free Hospital in
      London.
AB  - This paper provides a summary of a 6-year program of research by the Inflammatory
      Bowel Disease Study Group at the Royal Free Hospital and School of Medicine,
      London. Research has demonstrated: 1. That Crohn's disease is associated with
      profound damage to the mesenteric vascular blood supply, even in areas where
      tissue or bowel appear macroscopically normal; 2. That Crohn's disease is a
      granulomatous vasculitis; 3. That aphthous ulceration is due to damage to
      underlying blood vessels; 4. That Crohn's disease is associated with a
      hypercoagulable state, and that patients with hemophilia rarely develop Crohn's
      disease; 5. That measles virus genome is localized to foci of granulomatous
      vasculitis and lymphoid follicles in the bowel of patients with Crohn's disease.
      In conclusion, we have not proved that measles virus is the cause of Crohn's
      disease. Proof may be difficult until there is a specific anti-viral drug that is
      able to eradicate this RNA virus.

PMID- 8563890
TI  - Epidemiological study of ulcerative colitis in Japan: incidence and familial
      occurrence. The Epidemiology Group of the Research Committee of Inflammatory
      Bowel Disease in Japan.
AB  - Epidemiological studies of ulcerative colitis (UC) have been conducted once every
      year since 1973 in Japan. The number of participating hospitals in 1429 and they
      are distributed throughout Japan. A total number of 10819 patients diagnosed with
      UC have been registered, including 197 patients with a positive family history.
      In this present study, genetic or environmental factors that may be operative in
      the development of UC were investigated. After 1966, the annual incidence of UC
      increased rapidly, to a peak in 1974, tending to remain at the same level since
      1975. Since 1975, the daily intake of dairy products and meat increased,
      paralleling the increase in the incidence of UC. The trends of the increase in
      the incidence of UC and the increase in the daily intake of meat were very
      similar. The tendency for UC to occur in families was high, especially in first
      degree relatives, and the age at onset of UC in patients where there was familial
      occurrence was younger. There was no difference in HLA antigens between UC
      patients with familial occurrence and the unaffected relatives studied. It is
      presumed that not only genetic factors but also environmental factors may be
      operative in the development of UC.

PMID- 8563891
TI  - Enhanced interferon-gamma production and B7-2 expression in isolated intestinal
      mononuclear cells from patients with Crohn's disease.
AB  - Many of the in vivo activities of interferon (IFN)-gamma match the changes found
      in inflammatory bowel disease, but its importance is controversial. Interferon
      (IFN)-gamma induces the expression of B7-2 costimulatory molecules on monocytes.
      We measured levels of IFN-gamma production in intestinal mucosa and isolated
      lamina propria mononuclear cells (LPMC) in patients with Crohn's disease (CD) and
      ulcerative colitis (UC). We also investigated the induction of B7-2 on the LPMC
      by flow cytometry. Mucosal IFN-gamma production was higher than the control level
      in patients with CD, but this was not the case in UC. IFN-gamma production and B7
      2 expression in the LPMC of CD were higher than in the LPMC of UC and controls,
      and high levels of B7-2 expression were observed on the LPMC of CD after
      incubation with endotoxin. The induction of B7-2 on the LPMC of CD may provide a
      mechanism for the amplification of T cell proliferation and lymphokine production
      by IFN-gamma-activated LPMC.

PMID- 8563892
TI  - The role of proinflammatory and immunoregulatory cytokines in the pathogenesis of
      ulcerative colitis.
AB  - We investigated the production of proinflammatory cytokines (IL-1 beta, IL-6, IL
      8, and TNF-alpha) and immunoregulatory cytokines (IL-2, IFN-gamma, and IL-10) in
      the colonic mucosa of patients with active ulcerative colitis (UC), inactive UC,
      and non-inflammatory bowel disease (IBD) colitis by organ culture. The production
      of proinflammatory cytokines was significantly increased in all the studied
      groups compared with controls. In active UC, levels of these cytokines, except
      for IL-1 beta, were markedly increased compared with non-IBD colitis, and the
      levels were positively correlated with the degree of inflammation. Patients with
      non-refractory active UC receiving steroids showed levels of IL-1 beta and TNF
      beta production similar to those in controls. IL-10 production was also
      significantly increased in all the studied groups, the value of being the highest
      in active UC. In contrast, IL-2- and IFN-gamma production was significantly
      decreased in both active and inactive UC compared with controls, and the values
      in active UC were inversely correlated with the degree of inflammation. In non
      IBD colitis, decreased IL-2 production was observed, but IFN-gamma production did
      not differ from that in controls. In an experimental study, each of the
      proinflammatory cytokines was injected into the colonic mucosa of rats. All of
      these proinflammatory cytokines, except for IL-1 beta induced colonic mucosal
      damage that showed some histologic features similar to those of UC. These results
      suggest that the increased production of proinflammatory cytokines, particularly
      of IL-6 and IL-8, and the decreased production of IL-2- and IFN-gamma, probably
      downregulated by the enhanced production of IL-10, play an important role in the
      pathogenesis of UC.

PMID- 8563893
TI  - Study of cytokines in ulcerative colitis.
AB  - We investigated the lymphocyte-activation antigens and the expression of cytokine
      genes in the mucosa of ulcerative colitis (UC). Fresh colonic mucosal biopsy
      specimens from patients with UC and controls were fixed for the
      immunohistochemical study of CD4, HLA-DR, and CD25, and other specimens were
      prepared for the RNA analysis of cytokines. Gene expression was evaluated by the
      reverse transcription-polymerase chain reaction, and the radioactivity of dot
      blotted amplified cDNA was standardized by co-amplified beta-actin cDNA. The
      inflamed mucosa of active UC showed increased CD4+DR+ and CD25+ cells in
      comparison with control subjects. Active UC showed significantly increased mRNA
      expression of IL-1 beta, IL-2R alpha, IL-6, IL-8, and TNF alpha compared with the
      controls. We found no significant difference in the mRNA expression for IL-2, IL
      4, IL-10, and IFN-gamma between active UC and controls. Increased CD4+DR+ and
      CD25+ cells in active UC mucosa indicate mucosal CD4(+) T cell activation in the
      lamina propria, but we did not clarify Th1 or Th2 specific T cell activation from
      our study of cytokine mRNA expression. The increased mRNA expression for IL-1
      beta, IL-6, and TNF alpha in the mucosal lesions of UC indicates that these
      inflammatory cytokines may play important roles in the pathogenesis of UC.

PMID- 8563894
TI  - Activation of eosinophils in the pathophysiology of ulcerative colitis.
AB  - We studied the role of eosinophils as effector cells in the pathophysiology of
      ulcerative colitis. In the active stage of this disease, the colonic mucosa
      exhibited infiltration of numerous eosinophils positive to the EG2 antibody,
      which reacts specifically with the secretory form of eosinophil cationic protein.
      Electron microscopic studies demonstrated that the eosinophils had specific
      granules in various stages of degranulation. Hence, it is strongly suggested that
      the eosinophils infiltrating the inflamed mucosa are activated and may induce
      tissue damage during the degranulation and release of this cationic protein.
      Changes in the levels of serum eosinophil cationic protein in 14 patients who
      remained for in long-term remission were studied. Four of these patients showed
      persistently high concentrations of eosinophil cationic protein (equal to or
      greater than 30 micrograms/l) and persistently high percentage (mean, 30.2%) of
      hypodense eosinophils (specific gravity < 1.082) in the peripheral blood. Such
      findings were associated with mild active disease at colonoscopy. These features
      suggest that the activation of eosinophils is one of the factors that contribute
      to the chronic inflammation in ulcerative colitis.

PMID- 8563895
TI  - T cell adherence and mucosal injury in ulcerative colitis: involvement of
      integrin-fibronectin interaction in situ.
AB  - The mechanism whereby mononuclear cells, including T lymphocytes, accumulate in
      the mucosal lesions of patients with ulcerative colitis (UC) is unknown. Although
      the role played by vascular adhesion molecules in the abnormal recruitment of
      leukocytes has been emphasized, it does appear that fibronectin (FN), an
      extracellular matrix (ECM) protein, can play an important role in the persistence
      of active inflammation because of its effects on the proliferation,
      differentiation, and migration of cells. beta 1-integrins (VLA proteins) mediate
      cell adhesion to ECM proteins such as fibronectin, laminin, and collagen.
      Peripheral blood T lymphocytes (PBL-T) showed increased expression of VLA
      proteins after activation, although the expression of VLA proteins by lamina
      propria lymphocytes (LPL) is not known. In an in-vitro binding assay, PBL-T
      showed increased adherence to inflamed mucosa from patients with UC after
      stimulation with CD3 crosslinking. This adherence was partially inhibited by
      antibodies specific for plasma FN, VLA-4, VLA-5, and VLA-beta 1, and by the
      synthetic peptide RGDS. These findings suggest that infiltrating T cells derived
      from blood use FN receptors to anchor at inflammatory sites. It is conceivable
      that the inhibition of T cell adherence to ECM by antibodies or synthetic
      peptides could suppress inflammatory activity in UC.

PMID- 8563896
TI  - CD4+ intestinal mucosal lymphocytes in the pathogenesis of Crohn's disease.
AB  - To analyze the nature of intestinal mucosal lymphocytes in Crohn's disease, we
      established T cell lines of patients' intraepithelial lymphocytes. T cell lines
      from the affected terminal ileum of the patients showed an increased proportion
      of CD4+V beta 5.2/5.3+ T cells. These cells were increased in number after
      stimulation with staphylococcal enterotoxins C1 and D, showed an increase in
      cytolytic activity, and produced a large amount of interferon-gamma. To clarify
      the role of CD4+ mucosal lymphocytes in the intestinal inflammation, we then
      developed a novel colitis model by immunizing a rat with trinitrobenzenesulfonic
      acid (TNB) emulsion with adjuvant. Deep ulceration and granuloma formation in
      this colitis model resembled the histopathological findings of human Crohn's
      disease. Immunohistochemical and flow cytometric analysis demonstrated that the
      number of CD45RC(high)CD4+ mucosal lymphocytes was increased. Interestingly, the
      administration of anti-CD4 Abs prevented severe inflammation in the model. After
      treatment with anti-CD4 Abs, the anti-TNB Ab titer, the number of
      CD45RC(high)CD4+ cells, and interferon-gamma mRNA expression were significantly
      decreased in the mucosa of the model. These results suggest that some subsets of
      CD4+ mucosal lymphocytes play an important role in the triggering and progression
      of inflammation in Crohn's disease.

PMID- 8563897
TI  - Immunohistochemical localization of transforming growth factor-beta receptors I
      and II in inflammatory bowel disease.
AB  - Transforming growth factor (TGF)-beta inhibits cell proliferation and stimulates
      cell differentiation. For the signal transduction of TGF-beta, receptors I and II
      are required. The present study discloses the immunohistochemical localization of
      TGF-beta receptors I and II in inflammatory bowel disease. In the normal colon
      and small intestinal tissue, TGF-beta receptors were expressed in the epithelial
      cells in the upper crypts. In inflammatory bowel disease, a disordered expression
      pattern of receptors I and II was observed in the epithelial cells. Fibroblasts
      in the area of early stage fibrosis were positive for both receptors, while
      fibroblasts in area of advanced fibrosis lacked immunoreactivity for both
      receptors. Our study suggests that TGF-beta receptors I and II are important for
      the initial step of fibrosis.

PMID- 8563898
TI  - Immunology of inflammatory bowel disease--an update.

PMID- 8563899
TI  - Efficacy of nutritional therapy for active Crohn's disease.
AB  - We investigated the effect of nutritional therapy with an elemental diet (ED) for
      active Crohn's disease. One hundred and thirty-nine patients with Crohn's disease
      were enrolled in this study. Remission was judged to be present when the
      International Organization of Inflammatory Bowel Disease score was < or = 1 and
      the CRP and ESR values were within the respective normal ranges. An amount of
      30kcal per 1kg of ideal body weight (IBW) per day was administered enterally, and
      the effect on the induction of remission in relation to various patient
      background factors, such as disease type, history of bowel resection, and the
      presence/absence of complications, was determined. An excellent remission rate
      was achieved in those patients to whom an adequate amount of ED could be
      administered. Remission rates were lower in the patient groups with any of the
      following complications: stenotic bowel lesions, abdominal masses, fistulas, and
      anal lesions. Even in those groups in which stenotic lesions or abdominal masses
      were present, when adequate amounts of ED could be administered, the remission
      rate did not differ from that in the groups without these complications. The
      remission rates in the groups with and without fistulas at any site, including
      fistulas in the anal region, were 40.0% and 82.5%, respectively, with remission
      being considerably easier to achieve in the patients without fistulas. Similarly,
      remission was difficult to achieve when anal lesions were present. These results
      suggest that, for active Crohn's disease, nutritional therapy with ED ( > or =
      35kcal/kg IBW) should be enthusiastically administered, and in patients in whom
      the presence of complications necessitates therapy for 3 months or more, this
      point be considered to indicate a possible surgical approach.

PMID- 8563900
TI  - Therapeutic efficacy of elemental enteral alimentation in Crohn's fistula.

PMID- 8563901
TI  - A case-control study of ulcerative colitis in relation to dietary and other
      factors in Japan. The Epidemiology Group of the Research Committee of
      Inflammatory Bowel Disease in Japan.
AB  - The etiology of ulcerative colitis is essentially unknown. A hospital-based case
      control study examined the risk of ulcerative colitis in relation to dietary and
      other factors. Recruited at 20 hospitals across the nation were 101 ulcerative
      colitis patients who were 10-39 years old at the time of disease onset and whose
      disease had been diagnosed within the past 3 years. One hundred and forty-three
      control subjects were also examined. Information on factors was obtained by using
      a self-administered questionnaire. Combined consumption of western foods (bread
      for breakfast, butter, margarine, cheese, meats, and ham/ sausage) was
      significantly related to an increased risk of ulcerative colitis (trend P =
      0.04). Of the six food items of the western food group, margarine was positively
      and significantly associated with ulcerative colitis (trend P = 0.005), and bread
      for breakfast tended to be positively associated with the risk (trend P = 0.07).
      No appreciable association was found for the consumption of Japanese foods,
      vegetables and fruits, confectionery, or soft drinks. Compared with lifelong
      nonsmokers, current smokers had a decreased risk, and former smokers had an
      increased risk. This study confirmed a protective association between smoking and
      ulcerative colitis, and suggested that margarine or chemically modified fat may
      play an etiological role in the development of ulcerative colitis.

PMID- 8563902
TI  - Therapeutic efficacy of cyclic home elemental enteral alimentation in Crohn's
      disease: Japanese cooperative Crohn's disease study.
AB  - Crohn's disease (CD) often flares up and requires frequent hospitalization and/or
      surgery. Cyclic home elemental enteral alimentation (C-HEEA) was developed to
      prevent flare-up of CD and to minimize patient hospitalization. However, its
      therapeutic efficacy has not been studied in a large patient population.
      Therefore, questionnaires were sent to members of the Inflammatory Bowel Disease
      (IBD) Research Group of Japan to evaluate the therapeutic efficacy of C-HEEA and
      to define the factors that may affect the efficacy of the treatment. Data for 410
      patients (C-HEEA-treated n = 322; drug-treated n = 88) were collected from 29
      institutions and analysis showed the following results. The cumulative remission
      and non-hospitalization rates of the C-HEEA treated group were significantly
      higher than the rates of the drug-treated group in all patients and in those with
      ileitis and ileo-colitis (P < 0.0001, P < 0.001, and P < 0.01, respectively), but
      no significant difference was noted in patients with colitis. Cumulative
      remission and non-hospitalization rates were also influenced by the daily calorie
      content of the elemental diet (ED); more than 1200 kcal of the ED per day was
      found to be more effective than lower amounts to maintain remission and to
      prevent hospitalization. The therapeutic efficacy of C-HEEA was shown to be
      superior to that of drug treatment in patients with CD with ileal involvement,
      and it is suggested that more than 1200kcal per day should be supplied by the ED
      to enhance its therapeutic efficacy.

PMID- 8563903
TI  - Indications and options of nutritional treatment for Crohn's disease. A
      comparison of elemental and polymeric diets.
AB  - Several studies on enteral nutrition undertaken by our group led to the following
      findings: (1) A semielemental diet was as effective as an elemental diet in
      inducing remission. (2) A low-residue diet was useful for the maintenance of
      remission, with the effect depending upon the quantity given. (3) Intractability
      to enteral nutrition was found in patients with long-standing disease, in those
      with severe activity, and in those with colonic disease. Currently there is
      insufficient evidence to make specific recommendations for altering accepted
      indications for nutritional therapy.

PMID- 8563904
TI  - Therapeutic efficacy of N-3 polyunsaturated fatty acid in experimental Crohn's
      disease.
AB  - We investigated the therapeutic efficacy of n-3 polyunsaturated fatty acids
      (PUFAs) on trinitro-benzene sulfonic acid (TNBS)-induced colitis in the rats,
      which condition is considered an experimental Crohn's disease (CD). In rats with
      TNBS-induced colitis, feeding with an elemental diet (ED) plus 2% n-3 PUEA-rich
      perilla oil significantly suppressed plasma leukotriene (LT) B4 and ulcer index
      compared to that in rats fed with ED plus 2% n-6 PUFA-rich safflower oil (34.2 +/
      12.3 s 63.8 +/- 13.2 pg/ml and 8.8 +/- 12.1 vs 66.4 +/- 33.1, P < 0.01,
      respectively). Moreover, the plasma LTB4 and the ulcer index were significantly
      correlated (P < 0.05). Feeding with ED plus 2% alpha-linolenic acid (A-LA)-rich
      vegetable oil significantly reduced plasma LTB4 and colonic weight compared to
      that in rats fed with ED plus 2% eicosapentaenoic acid (EPA)/docosahexaenonic
      acid (DHA)-rich fish oil in this model (61.6 +/- 10.5 vs 85.0 +/- 20.9 pg/ml and
      0.83 +/- 0.13 vs 0.96 +/- 0.08g, P < 0.05, respectively). This study suggested
      that dietary fat manipulation with perilla oil can reduce colonic damage and that
      this is correlated with the suppression of plasma LTB4. The therapeutic efficacy
      of A-LA in controlling intestinal inflammation in experimental CD may be superior
      to that of EPA and DHA.

PMID- 8563905
TI  - [The irradiation levels of the participants in the cleanup of the aftermath of
      the Chernobyl accident in 1986-1987 and the verification of the dosimetric data].
AB  - It is considered the organization of individual dosimetric monitoring (IDM)
      within 30-km zone around Chernobyl nuclear power plant (CNPP) in 1986 for
      different contingents of recovery workers: the CNPP personnel, Management for
      Construction 605 (MC-605), military recovery workers, persons assigned to 30-km
      zone. It is concluded that the quality of IDM had decreased in the following
      series: the MC-605 personnel, the CNPP personnel, the assigned persons, and
      military units. The method of dosimetric data verification for recovery workers
      in 1986 is presented which is based on the analyses of the dependency H(delta)/In
      delta from delta, where delta is a step of the histogram of distribution, and
      H(delta) is delta-entropy of distribution. The results obtained by this method
      correspond to the results of the experts' estimation. It was shown that 60% of
      registered individual doses for the whole contingent of the recovery workers
      differ from the real exposure doses. Using the theory of hybrid lognormal
      distribution it was obtained, in our opinion, real external dose distribution for
      all the recovery workers. It was estimated that 7% of recovery workers received
      doses more than 0.25 Gy. Also, the data on values of mean and collective doses
      for different contingents, as well as for all persons involved in recovery
      operations is presented.

PMID- 8563906
TI  - [The differential possibilities of the laser correlational spectroscopic method
      in the diagnosis of different pathological processes encountered among the
      population of the Urals radiation trace].
AB  - The satisfied differential distinctions between diseases (7 nosological groups)
      observed in population of so-called Ural radiation trace are established using
      laser correlation spectroscopy (LCS). Unsatisfied differentiation (less then 65%)
      was observed between cancer and pre-cancer diseases relative to gastric,
      bronchial and exchange pathologies. The most significant distinctions are
      established for autoimmune pathologies and osteochondroses and for cancer and pre
      cancer differentiation. Marked differentiation degree is less than that earlier
      registered between the same pathologies in regions, where radiation level was
      normal. On the base of the measurements is planned to study the dose effect of
      pathology radiomodification.

PMID- 8563907
TI  - [The dynamics of the radiation damage and recovery processes in coniferous stands
      in a 10-kilometer control zone of the accident at the Chernobyl Atomic Electric
      Power Station].
AB  - Properties of morphogenesis, growth dynamics, anatomy and ultrastructure of wood
      and needle, reproductive processes in coniferous plants were studied under
      different level of radiation effect in the 10-km zone in 1986-1992. It was
      established that the full drying of pine forests began under absorbed dose 80-100
      Gy/year. Threshold doses, after which repair processes were possible, reached to
      10-12 Gy/year for Picea abies and 50 Gy/year for Pinus sylvestris. Three maine
      stages are revealed in dynamics of radiation damage and repair processes in
      studied conifers and their morphological and functional characteristic is
      presented.

PMID- 8563908
TI  - [An assessment of the absorbed doses in cattle over the course of the first year
      after the accident at the Chernobyl Atomic Electric Power Station].
AB  - Absorbed doses of incorporated iodine and caesium radionuclides were evaluated in
      cattle animals which were within the Chernobyl accident spilling-out zone during
      the first year after the accident. The absorbed doses in animal thyroids were
      determined to range from 25 to 320 Gy. Some endemic features of this region
      promoted high absorbed dose accumulation in cattle thyroid. The dose per the
      whole body did not exceed 0.2 Gy. The absorbed doses in liver, kidney or spleen
      were about several cGy.

PMID- 8563909
TI  - [The lipid composition of the membrane of the brush border in the rat small
      intestine in the late period after gamma irradiation].
AB  - The lipid composition of membrane of the small intestine brush border was studied
      1, 2, 3 and 6 months after the whole-body fractionated gamma irradiation of the
      one-month-old rats of 80 g weight with a dose of 6 Gy (2 Gy x 3 at a week
      intervals). Three months after exposure the amount of cholesterol, total
      phospholipids, phosphatidylcholine, phosphatidyl-ethanolamine in brush border
      membrane was the same as in control. The role of phospholipids and cholesterol
      catabolism suppression in membrane regulatory function disturbances after
      irradiation is discussed.

PMID- 8563910
TI  - [The amount of lipids in the rat liver in the late period after fractionated
      exposure to gamma radiation].
AB  - Remote effects of fractionated irradiation (6 Gy) on the amount of lipids in the
      rat liver were observed during a period of six months following irradiation. It
      was shown, that amount of cholesterol in rat liver decreased during the first
      months following irradiation, and after 6 months was normal. The content of
      phospholipids is not changed throughout the entire period of observation.

PMID- 8563912
TI  - [The effect of chronic x-ray radiation at low doses on the gamma-glutamyl
      transpeptidase activity in rat organs and tissues].
AB  - Effect of chronic low dose X-ray irradiation (total doses of 2.58, 5.16, 6.46,
      7.75, 10.32 and 12.92 mC/kg) on gamma-glytamyltranspeptidase activity was
      investigated in rat organs and tissues which were different by radiosensitivity.
      Enzymatic activity was measured one hour after exposure. The increase in
      enzymatic activity was found in brain, liver, lungs, spleen, blood serum and
      partially in kidneys under all exposure doses. Exposure to 2.58, 5.16 and 12.92
      mC/kg inhibited gamma-glutamyltranspeptidase activity in small intestines.

PMID- 8563911
TI  - [The biochemical changes in the brain synaptosomes during the gamma irradiation
      of mice at a low dose with different intensities].
AB  - Some characteristics of mice brain nerve-endings' lipid phase were studied (total
      lipids, total and individual phospholipids and cholesterol contents, their
      ratios, lipid peroxidation level, rigidity index) after single low dose, whole
      body gamma-irradiation (15 cGy) with dose intensities of 0.01, 0.25, 9.0 cGy/min.
      Some markedly expressed alterations were found out in those parameters. Brain
      membranes functioning also changed significantly as it was judged by membrane
      bound acetylcholinesterase activity. All the changes revealed complicated
      dependence both on dose intensity and on time period after irradiation. The
      ranges of the observed changes suppose CNS state to have been modified by low
      dose irradiation including CNS sensibility to external psycho- and neurotrophic
      factors.

PMID- 8563913
TI  - [The phospholipase A2 hydrolysis of irradiated lipid membranes].
AB  - Phospholipase A2 hydrolysis of dioleoylphosphatidylcholine,
      dimyristoylphosphatidylcholine or their equimolar mixture with sphingomyelin in
      liposomes exposed to gamma-radiation has been investigated. Stabilization of the
      gamma-irradiated lipid bilayer to hydrolysis by sphingomyelin has been shown.

PMID- 8563914
TI  - [The action of radioprotectors of natural origin (MIGI-K and carnosine) on the
      catecholamine level in irradiated rats].
AB  - The influence of natural radioprotectors (MIGI-K and carnosin) on the dynamics of
      catecholamines level in adrenal glands of irradiated rats was shown. Carnosin and
      MIGI-K take part in developing of organism radioresistance. Carnosin action is
      due to mobilisation of endogenous radioprotective agents (catecholamines) while
      MIGI-K influences on the restoring of their level.

PMID- 8563915
TI  - [The postradiation restoration of the liver by using potable mineral waters].
AB  - In experiments with 135 white breed-less male rats it was shown that the drinking
      mineral waters containing sulphate or silic ions promoted the postradiated
      rehabilitation in the liver after whole-body 5 Gy gamma-ray exposure. The
      decrease of the rate of lipid peroxidation in hepatocyte membranes, the increase
      of quantity normal cells and the decrease of quantity dystrophic and necrobiotic
      cells, the change of haemostasis took place. The iodine- and boron-containing
      mineral waters were less efficacious in these processes than the waters with
      sulphate and silic ions.

PMID- 8563916
TI  - [A mathematical model of the changes in bone marrow cellularity in radiation
      exposures].
AB  - The model is based on classical ideas about of hemopoiesis in normal conditions
      and under irradiation. It consists of only two equations characterizing stem and
      differentiated bone marrow cell dynamics. The systemic mechanisms of hemopoiesis
      regulation were roughly taken into account. The formulae suitable for
      calculations of equilibrium cell concentrations under prolonged irradiation were
      derived. The model was shown to be in agreement with experimental data on
      hemopoietic system changes under acute and prolonged irradiation of rodents and
      dogs. The model is intended for describing the extent of hemopoiesis disturbance
      under those modes of mammalian exposure when describing of general regularities
      is enough.

PMID- 8563917
TI  - [The risk of developing mammary tumors in rats irradiated with accelerated
      charged particles and rare ionizing radiation. The RBE coefficients].
AB  - Frequency, development time and histological structure of mammary gland tumors
      were studied in rats irradiated with 645 MeV and 9 GeV protons, 4 GeV helium ions
      and 60Co gamma rays. The risk of the tumor development and the RBE coefficients
      were estimated.

PMID- 8563918
TI  - [The reaction of the systems of hormonal mediator regulation to a weak
      geomagnetic field against a background of ionizing radiation exposure].
AB  - Guinea pigs were subjected for 30 minutes to geomagnetic field of ten times
      decreased induction. The increase of epinephrine and histamine level in blood was
      observed. The decrease of histamine and serotonin concentration as well as
      normalization of epinephrine level were found when the influence of weakened
      geomagnetic field was stopped. Preliminary 2 Gy X-radiation resulted in the
      suppressed response of the organism to the weak geomagnetic field.

PMID- 8563919
TI  - Shortening of the metatarsal shaft in the treatment of plantar keratosis: an end
      result study. 1958.

PMID- 8563920
TI  - Treatment of symptomatic hammertoe with a proximal interphalangeal joint
      arthrodesis.
AB  - This study examined 76 consecutive patients (100 feet) treated by a single
      surgeon for both flexible and rigid hammertoes with a PIP arthrodesis using
      custom-machined drills, a peg cutter, and hole cutter, combined with an extensor
      tenotomy and dorsal capsulotomy. Forty-eight percent of patients were defined as
      satisfied without reservation, 37% were defined as satisfied with reservations,
      and 15% were defined as dissatisfied. The incidence of radiographic fusion was
      95% (130/137 toes). The most common reasons for either reservation or
      dissatisfaction included incomplete pain relief, residual toe angulation, and
      prolonged shoe wear restriction in the postoperative period. Based upon the
      results of this study, the authors suggest that when using a peg and socket
      arthrodesis for hammertoe correction (1) there is a 95% rate of radiographic
      fusion, (2) patients over 65 years old be alerted to a diminished rate of
      satisfaction, and (3) a distal flexor tenotomy be considered in patients with a
      preoperative DIP flexion contracture.

PMID- 8563921
TI  - Anatomic structures at risk: combined subtalar and ankle arthrodesis with a
      retrograde intramedullary rod.
AB  - Retrograde intramedullary rodding from the calcaneus, through the talus, and into
      the tibia is currently an evolving procedure being used for salvage of severe
      foot/ankle deformity, arthritis, tumor, and instability. In this study,
      retrograde rodding was performed on six cadaver specimens. The specimens were
      then dissected to determine the subcalcaneal structures at risk and the optimal
      insertion point for the rod. This study elucidated the structures most at risk
      and showed the optimal insertion site to be at the junction of the sustentaculum
      tali and the body of the calcaneus.

PMID- 8563922
TI  - Plantar fibromatosis: a review of primary and recurrent surgical treatment.
AB  - Plantar fibromatosis can be quite disabling to the patient, as well as a
      technical challenge to the surgeon. Patients who undergo previous local excisions
      and in whom aggressive recurrences develop are difficult to manage successfully.
      We present a consecutive series of five primary procedures on patients with
      painful plantar fibroma and seven revision operations on patients with recurrent
      plantar fibroma. The average follow-up was 47 months (range, 22-66 months) in the
      primary group and 40 months (range, 21-78 months) in the revision group. The
      overall results were satisfactory in four of the five primary operations, with
      only one recurrence. In the revision group, five of seven results were
      satisfactory with no recurrences. The major complication that led to
      unsatisfactory results was the development of a postoperative neuroma. In this
      article, we outline our present surgical techniques of wide primary excision and
      a staged revision procedure with delayed split-thickness skin graft closure.
      These techniques can be used successfully to manage this disabling, progressive
      disease.

PMID- 8563923
TI  - An anatomic analysis of endoscopic plantar fascia release.
AB  - Eighteen fresh-frozen cadaver foot specimens underwent release of the plantar
      fascia via a newly described endoscopic technique. A 75% release was attempted on
      each specimen in order to represent a partial fascial release. Each specimen was
      then dissected to assess the success of the procedure. Five separate measurements
      were recorded evaluating the reproducibility of the procedure, adequacy of the
      release considering accepted etiologies for chronic heel pain, and the
      possibility of damage to local structures. Partial release was noted to be
      possible, but controlling the exact percentage of the incision was difficult. The
      release averaged 82% of the width of the fascia, with a range of 53% to 100%.
      There was no damage in any specimen to the first branch of the lateral plantar
      nerve, the structure considered most at risk during the procedure. Release of the
      deep fascia of the abductor hallucis muscle was not possible with this approach.

PMID- 8563924
TI  - Irreducible dorsal dislocation of the great toe interphalangeal joint: case
      report and literature review.
AB  - Irreducible dorsal dislocation of the interphalangeal joint of the great toe is
      rare. Few case reports can be found in the literature. Most cases have been
      treated with operative exploration of the joint and reduction through a dorsal
      midline incision. We present a case where a medial approach was used under local
      block anesthesia to treat an irreducible complex dislocation of the
      interphalangeal joint of the great toe.

PMID- 8563925
TI  - A comparison of the dynamic pedobarograph and EMED systems for measuring dynamic
      foot pressures.
AB  - The purpose of this study was to compare the peak pressure and peak force values
      obtained from two pressure assessment systems, the Dynamic Pedobarograph and the
      EMED SF. Twenty-one individuals with a mean age of 31.6 years walked barefoot
      over both systems using a two-step data collection protocol. Peak plantar
      pressures and peak vertical force values were measured under the heel, central
      forefoot, hallux, and entire foot for both systems. The results of this study
      demonstrated that the EMED SF system produced larger peak pressures under the
      central forefoot and hallux. The Pedobarograph, on the other hand, produced
      greater pressures under the heel and entire foot. With respect to peak vertical
      forces, the Pedobarograph showed significantly greater values under the heel and
      central forefoot compared with the EMED SF, but were significantly lower under
      the hallux and entire foot.

PMID- 8563926
TI  - Influence of ligament transection on tibial and calcaneal rotation with loading
      and dorsi-plantarflexion.
AB  - The purpose of this study was to quantify the effect of sequential ligament
      transection (anterior talofibular, calcaneofibular, posterior talofibular,
      deltoid, and subtalar interosseous ligaments) on the rotational movement of the
      tibia and the calcaneus as associated with axial loading and dorsi-plantarflexing
      the foot. Eight cadaver foot-leg specimens were investigated using a
      unconstrained testing apparatus. As the ankle complex was axially loaded, almost
      the same internal rotation of the tibia and the same calcaneus eversion was found
      with and without the various degrees of lateral and medial ligament release;
      additional sectioning of the subtalar interosseous ligament tremendously
      increased the resulting tibial and calcaneal rotation. While tibial and calcaneal
      rotation from foot dorsi-plantarflexing did not alter significantly with
      transection of the lateral ligaments, almost no tibial and calcaneal rotation
      occurred after additional sectioning of the deltoid and subtalar interosseous
      ligament. These results indicate that, after release of the lateral ligaments,
      the foot becomes partially mechanically disconnected from the tibia by additional
      transection of the medial ligaments and even further disconnected after
      transection of the subtalar interosseous ligament.

PMID- 8563927
TI  - The hindfoot alignment view.
AB  - A modification of Cobey's method for radiographically imaging the coronal plane
      alignment of the hindfoot is described. Using this view, we estimated the moment
      arm between the weightbearing axis of the leg and the contact point of the heel.
      Normative data on 57 asymptomatic adult subjects are presented. The weightbearing
      line of the tibia falls within 8 mm of the lowest calcaneal point in 80% of
      subjects and within 15 mm of the lowest calcaneal point in 95% of subjects. The
      technique for measuring coronal plane hindfoot alignment is reliable, with an
      interobserver correlation coefficient of 0.97. This radiographic technique should
      help in the evaluation of complex hindfoot malalignments.

PMID- 8563928
TI  - Kinematics of the axially loaded ankle.
AB  - An apparatus that allowed the application of a 900 N axial load and the
      simultaneous measurement of rotation in the sagittal, coronal, and axial planes
      was used to study the normal kinematics of the ankle in 13 below-knee amputation
      specimens. Two testing routines were done on all specimens. In the first
      sequence, specimens were moved through a dorsiflexion (DF) and plantarflexion
      (PF) arc of 60 degrees (25 degrees DF and 35 degrees PF). DF was associated with
      an average of 2.5 degrees of external rotation, and PF was associated with an
      average of < 1 degree of internal rotation. In the coronal plane, PF and DF were
      both associated with < 1 degree of varus. In the second part of the testing, the
      ankle position in the sagittal plane (DF/PF) was fixed and the axial load was
      increased from 50 N to 750 N in 100-N intervals. Increasing the axial load caused
      an increase in external rotation and valgus of 1 degree to 2 degrees. For axial
      rotation, external rotation was more pronounced in PF than DF. The effect of load
      on the increase on valgus was not affected by sagittal ankle position. The effect
      of increasing axial load on sagittal rotation was to increase DF or PF < 2
      degrees over the entire range of loads and sagittal positions. The understanding
      of ankle biomechanics is essential to the formulation of rational guidelines for
      the treatment of ankle pathology and the prediction of the long-term consequences
      of ankle injuries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8563929
TI  - Traumatic talectomy without fracture: four case reports and review of the
      literature.

PMID- 8563930
TI  - Non-neoplastic nodular lesions in the liver.
AB  - The classical nomenclature and categorization of neoplastic and non-neoplastic
      nodular lesions of the liver are being revised due to the tremendous volume of
      information recently published on this issue. The diagnostic histopathology of
      non-neoplastic nodular (tumor-like) lesions of the liver that are recognizable in
      biopsied, surgically resected and autopsied livers is reviewed using current
      terminology. Generally, such nodules are infrequent and even rare in routine
      liver specimens. Non-neoplastic nodules include focal nodular hyperplasia,
      nodular regenerative hyperplasia, compensatory hyperplasia of the liver,
      pseudonodule of the liver demonstrable by angiography, partial nodular
      transformation, focal fatty change, nodular hepatic area shown by modified
      angiography, cirrhotic large regenerative nodule with variable atypia, anoxic
      pseudolobular necrosis, intrahepatic bile duct adenoma, biliary and mesenchymal
      hamartoma, and mesenchymal nodular lesions such as inflammatory pseudotumor and
      pseudolymphoma, pseudolipoma, peliosis hepatis, solitary necrotic nodule, and so
      on. Some of these develop preferentially in non-cirrhotic or cirrhotic livers,
      while others occur with similar prevalence in cirrhotic and non-cirrhotic livers.
      Some occur multiply or diffusely and others singly. As to the pathogenesis of
      these nodules, it is speculated that hyperplasia due to disturbed intrahepatic
      circulation or hormonal imbalance, preneoplastic characteristics, abnormal
      metabolic disturbance, hamartoma or focal necrobiotic processes, and infection
      have a role. Knowledge and awareness of these non-neoplastic nodular lesions are
      necessary for precise diagnosis and differentiation of these nodular lesions from
      neoplastic hepatic nodules.

PMID- 8563931
TI  - Expression of vascular permeability factor (VPF/VEGF) messenger RNA by plasma
      cells: possible involvement in the development of edema in chronic inflammation.
AB  - Edema occurs in some types of chronic inflammation such as nasal polyps, uterine
      cervical polyps and gastric hyperplastic polyps. However, the factors or cellular
      components involved in the development of edema in chronic inflammation remain to
      be clarified. Recently, the gene encoding vascular permeability factor (VPF) or
      vascular endothelial growth factor (VEGF) and the genes encoding its receptors
      (kinase insert domain-containing receptor (KDR) and fms-like tyrosine kinase-1
      [fit-1]) have been cloned. VPF/VEGF induces vascular hyperpermeability and
      vascular endothelial proliferation through KDR or fit-1 receptors. As there is a
      possibility that VPF/VEGF may play a role in the development of edema in chronic
      inflammation, we examined the messenger (m) RNA expression of VPF/VEGF and its
      receptors in nasal polyp tissues, which is an example of chronic inflammation
      with remarkable edema. Using northern blotting, all nasal polyp tissues examined
      expressed mRNA of VPF/VEGF and KDR. In situ hybridization revealed that VPF/VEGF
      mRNA-expressing cells were scattered in the edematous stroma of nasal polyps. In
      the adjacent sections, these cells showed the morphological features of plasma
      cells and expressed mRNA of immunoglobulin light chains. Human B cell leukemia
      and plasmacytoma cell lines expressed VPF/VEGF mRNA but human mast-cell leukemia
      and T cell leukemia cell lines did not. The alternatively spliced pattern of
      VPF/VEGF transcripts observed in nasal polyp tissues was consistent with that in
      plasmacytoma cell lines. Taken together, the VPF/VEGF mRNA-expressing cells in
      nasal polyps appeared to be plasma cells, suggesting that plasma cells may play
      an important role in the development of edema in chronic inflammation through the
      production of VPF/VEGF.

PMID- 8563932
TI  - Cell death in colorectal polyps as evaluated by in situ 3'-tailing reaction and
      its relationship to BCL-2 expression.
AB  - Colorectal polyps were analyzed from the standpoint of cell death by using the in
      situ 3'-tailing reaction (ISTR), which identifies cell death-associated DNA
      double strand breaks, and immunohistochemistry for bcl-2 oncoprotein (BCL-2) and
      for Ki-67. There were few ISTR-positive cells in the non-neoplastic glands,
      whereas 38% of non-neoplastic mucosa just adjacent to the adenoma had many
      labeled nuclei, suggestive of cell death associated with replacement by tumor.
      The neoplastic glands contained variable number of ISTR-positive nuclei, mostly
      showing the morphological feature of apoptotic bodies. In the representative
      glands with the most prominent ISTR-labeling, their indices did not have a
      significant relationship to the grade of atypia, to the proliferative activity
      (Ki-67 labeling indices) of neoplastic glands, or to BCL-2 stainability. In each
      case, however, the neoplastic glands with no or few ISTR-labeled nuclei tended to
      express BCL-2 intensely, and all lesions of adenoma or carcinoma with more than
      15% of ISTR-labeling indices showed weak BCL-2 immunoreactivity. In general, BCL
      2 expression was significantly stronger in the adenoma than in non-neoplastic
      mucosa and carcinoma, although there was no significant difference of ISTR
      labeling between adenoma and carcinoma. These results indicate that cell death in
      colorectal neoplastic polyps does not have a significant influence on their
      growth rate, and that BCL-2 plays some role, at least in part, in the regulation
      of apoptosis.

PMID- 8563933
TI  - Apoptosis in histiocytic necrotizing lymphadenitis.
AB  - Cell death can now be divided into necrosis and apoptosis, which are different in
      their morphology, biochemistry and biological significance. The present study was
      designed to investigate cell death in histiocytic necrotizing lymphadenitis
      (HNL). The features of cell death in 10 cases of HNL were analyzed using
      histiomorphology, ultrastructure and in situ apoptosis detection (ApopTag)
      methods. Two patterns of cell death were discerned. One was apoptosis of
      individual cells and the other was necrosis. The first pattern could be observed
      in all cases and the morphological features of the dead cells were consistent
      with those of apoptosis, which included distinctive cell volume shrinking and
      chromatin condensation. The apoptotic cells and bodies could frequently be found
      to be phagocytosed by the histiocytes. ApopTag was positively stained in most of
      the morphologically apoptotic cells. By double staining, most ApopTag positive
      cells were found to be T lymphocytes. A previous report showed that the majority
      of the proliferative cells were T lymphocytes. Based on those results, if was
      speculated that the main pathological characteristics of HNL therefore consisted
      of apoptosis and the proliferation of T lymphocytes.

PMID- 8563934
TI  - Epstein-Barr virus genomes in Hodgkin's disease and non-Hodgkin's lymphomas.
AB  - Seventeen of 40 cases of Hodgkin's disease (HD) and eight of 46 non-Hodgkin's
      lymphomas (NHL) were associated with Epstein-Barr virus (EBV) infection, judged
      by the EBER-1 in situ hybridization (ISH) method. Approximately 40% incidence in
      HD was comparable to previous reports. Young children and elderly HD patients
      were more prone to be found EBV positive. Fourteen of 17 HD and two of 8 NHL
      cases with positive EBER-1 ISH were also positive on LMP-1 immunostaining. EBV
      might have a role in lymphomagenesis in these cases. The fact that 7 of 8 EBV
      related NHL were peripheral T cell lymphoma indicates the necessity of a larger
      scale survey on this subject. As the present study revealed four cases with
      positive LMP-1 immunostaining but negative EBER-1 ISH (1 HD, 3 NHL), LMP-1 alone
      should not be regarded as a tool to prove EBV infection.

PMID- 8563935
TI  - Increased S-100 protein-immunoreactivity of Kupffer cells is associated with
      lymphohematological malignancy.
AB  - The distribution of S-100 protein in normal tissue has been studied extensively.
      However, little is known about its expression in pathologic states. The aim of
      the present study was to investigate the expression of S-100 protein in diseased
      human liver, especially in Kupffer cells. One hundred cases of autopsy livers
      originating from patients with various diseases were examined. Increased S-100
      immunoreactivity of Kupffer cells was observed in six cases. Of the six cases,
      four were derived from a lymphohematologic malignancy, such as B cell lymphoma, B
      cell lymphoblastic leukemia, multiple myeloma and chronic myelogenous leukemia
      with lymphoblastic crisis. Lymphohematologic malignancy accounted for 16 out of
      the 100 cases examined. Thus, increased S-100-positive Kupffer cells was
      significantly associated with lymphohematologic malignancy (P < 0.01); 25% (4/16)
      in cases with lymphohematologic malignancy versus 2.4% (2/84) in the remaining
      cases. Moreover, some of these S-100-positive Kupffer cells were positive for S
      100 beta-subunit, which is not normally expressed by Kupffer cells. Although the
      reason for this increased S-100-immunoreactivity is speculative, the authors'
      hypothesis is that tumor cells may produce some factor(s) that induce the
      expression of S-100 protein in Kupffer cells.

PMID- 8563936
TI  - Expression of immunoreactivities to 75 kDa nerve growth factor receptor, trk gene
      product and phosphotyrosine in granular cell tumors.
AB  - Nineteen granular cell tumors (GCT) of adults, two congenital granular cell
      epulides and five epulides fibrosae were immunohistochemically examined to detect
      the expression of 75 kDa nerve growth factor receptor (NGFR), trk gene product,
      phosphotyrosine (PT), protein gene product 9.5 (PGP9.5) and S-100 protein. The
      NGFR-immunoreactivity (IR) and trk gene product-IR were expressed on almost all
      granular cells of GCT. PT-IR was also demonstrated on granular cells of all GCT
      examined, although the frequency of positive cells was low. Congenital granular
      cell epulides and epulides fibrosae were negative for NGFR-IR, trk gene product
      IR and PT-IR. S-100 protein was localized in granular cells of adult GCT but not
      in the granular cells of congenital epulis. On the other hand, PGP9.5 was
      detected in granular cells of both conditions and in fibroblastic cells of epulis
      fibrosa. The present results further indicate that GCT is of peripheral nerve
      Schwann cell origin, while the congenital granular cell epulides are not of
      neural origin. NGFR and trk gene product expressed on GCT seems to be functional
      in terms of phosphorylation of the tyrosine residue in the receptor or downstream
      protein in signal transduction.

PMID- 8563937
TI  - Intussusception of the appendix: a report of three cases with different clinical
      and pathologic features.
AB  - Three cases of intussusception of the appendix (IA) with distinctive pathologic
      changes were reported. All patients were women with different clinical
      presentations. Grossly, a complete intussusception was found in one case (case
      1), while the others (cases 2 and 3) showed a partial intussusception. In case 1,
      almost the total segment of the appendix bearing the villous adenoma with focal
      malignant transformation became completely telescoped into the cecum. In case 2,
      no underlying appendiceal lesion was disclosed. In case 3, appendiceal
      endometriosis was found as the point of traction. Awareness of such a rare
      complication associated with various appendiceal lesions provides a clue for
      making an accurate diagnosis and selecting appropriate surgical management.

PMID- 8563938
TI  - Langerhans' cell histiocytosis of the lung in association with mediastinal
      lymphadenopathy.
AB  - A 17 year old female was seen because of a non-productive cough and one episode
      of blood-tinged sputum. A computerized tomography (CT) scan of the chest showed
      multiple small cystic lucencies in the upper lobes. The mediastinal CT window
      revealed concurrent mediastinal lymphadenopathy. An open lung biopsy showed
      Langerhans' cell histiocytosis (LCH). The significance of nodal involvement in
      LCH of the lung is not known, but raises the possibility of regional LCH and
      warrants a further search for bone or visceral involvement as well as closer
      follow-up and monitoring of patients.

PMID- 8563939
TI  - Sebaceous carcinoma of the vulva.
AB  - Extraocular sebaceous carcinoma (SC) is a rare tumor usually found on the head
      and neck. A 78 year old Japanese female who had an asymptomatic vulvar tumor is
      reported here. The excised specimen showed SC with metastasis to the inguinal
      lymph nodes. This is the fourth reported case of SC arising from female
      genitalia, and the second case that apparently arose from the labia minora.
      Contrary to the previously reported cases, tumor cells in the present case had
      abundant glycogen. Thus, differential diagnosis of SC from metastatic renal cell
      carcinoma is difficult morphologically because both of them have glycogen and
      lipid. Intraepidermal invasion of tumor cells has been reported in SC, but a
      suspected lesion of this phenomenon in the present case was proved to be
      histiocytic infiltration by immunohistochemistry using anti-CD 68 antibody.

PMID- 8563940
TI  - Histiocytoid cardiomyopathy with hypotonia in an infant.
AB  - A 15 month old female, who had suffered from ventricular tachycardia from the
      prenatal period, experienced cardiac arrest at home. Once she had recovered,
      ventricular tachycardia occurred repeatedly. She died 7 months after admission.
      At autopsy, the heart showed many yellowish white nodules in the endocardium.
      Histologically these nodules consisted of granular or foamy histiocyte-like
      cells, which had spread to all four chambers. Electron micrographs showed
      mitochondrial hyperplasia in these cells. The cells had some myofibrils in their
      cytoplasm. These findings were compatible with histiocytoid cardiomyopathy.
      Interestingly, the present case showed hypotonia. Her muscle biopsy revealed
      decreased activity of cytochrome c oxidase, suggesting that histiocytoid
      cardiomyopathy is related to mitochondrial cytopathy.

PMID- 8563941
TI  - Pathological and immunohistochemical findings in a case of mucinous
      cholangiocarcinoma.
AB  - A case of mucinous cholangiocarcinoma is reported. The patient was a 49 year old
      woman with the complaint of lumbago. Imaging examination disclosed a tumor 3.5 cm
      in diameter in the right hepatic lobe, which showed low density on computerized
      tomography scans and low signal intensity on T1-weighted magnetic resonance
      imaging (MRI) and high intensity on T2-weighted MRI. The hepatic tumor expanded
      rapidly and multiple pulmonary metastases and peritoneal dissemination developed.
      The patient died due to respiratory failure 5 months after the initial symptom.
      An autopsy, a massive tumor (9.5 cm in diameter) containing abundant mucus with
      several surrounding daughter nodules was found in the right hepatic lobe.
      Metastases were widespread. Histologically, the tumor was composed mainly of
      numerous lobulated mucus lakes in which adenocarcinoma cells floated. Admixed
      signet ring cells were also noted. These gross and histologic features differ
      from those in other mucin-producing hepatic tumors such as biliary papillomatosis
      and mucinous cystoadenocarcinoma. Immunohistochemically, the adenocarcinoma cells
      were strongly positive for carcinoembryonic antigen, Lewis Y, Tn, and T antigens
      and moderately positive for carbohydrate antigen 19-9, Lewis X, sialyl-Lewis X
      and sialyl-Tn antigen. Mature MUC1 mucin and core protein of MUC1 mucin were also
      expressed to varying degrees. The rapidly expanding, widespread metastases and
      poor prognosis found in the present case may be the clinicopathological features
      of mucinous cholangiocarcinoma.

PMID- 8563942
TI  - Expression of CA15-3 in renal cell carcinoma.
AB  - CA15-3 expression was analyzed in renal cell carcinoma (RCC) from the standpoint
      of the histogenesis of RCC. Tissue sections from surgical specimens of 12 cases
      of clear cell type RCC and from autopsy specimens of eight fetal kidneys were
      stained by an indirect immunoperoxidase method using DF-3. All the RCC cases
      stained positively for CA15-3, with 10 of the 12 cases showing strong, diffuse
      immunoreactivity on the cell membrane. Expression of CA15-3, as well as other
      markers such as epithelial membrane antigen, neuron-specific enolase, glandular
      cytokeratin and other lectins, suggest a more complicated histogenesis of RCC,
      rather than a simple proximal tubular origin.

PMID- 8563943
TI  - Characterization of lipopolysaccharides from Pseudomonas syringae (serogroup II).
AB  - Lipopolysaccharides (LPS) from the strains of Pseudomonas syringae pv.syringae
      90a, 435, pv. atrofaciens K-1025, pv. morsprunorum CF-4 referred by Pastushenko
      and Simonovich (1979) to serogroup II have been studied. The strains were shown
      to be heterogeneous by chemical composition of core and lipid A and structure of
      O-specific polysaccharide. The preparations heterogeneity in serological cross
      reactions were also detected. O-specific polysaccharides of the strains having
      similar structures were not identical in serological tests. The assumption on the
      lipid A role in serogrouping of P. syringae strains has been advanced.

PMID- 8563944
TI  - [Gram-negative bacteria contaminating the process of producing lysine].
AB  - The authors have isolated Gram-negative bacteria of the Enterobacteriaceae family
      from the culture liquid of industrial fermenters with low yield of lysine. Most
      of them possessed the characters typical of Klebsiella pneumoniae and Escherichia
      coli, the rest were identified as the representatives of genera Proteus,
      Providencia, Enterobacter, Hafnia. Strains of Klebsiella pneumoniae, E.coli,
      Proteus rettgeri manifested lysine-decarboxylase activity. The capacity of some
      strains to destruct lysine synthesized by the target culture in the process of
      fermentation with formation of cadaverin was experimentally proved and confirmed
      under production conditions. Technological water is the source of distribution of
      gram-negative bacteria (first of all Klebsiella) in lysine production.

PMID- 8563945
TI  - [The characteristics of the lipid A of the lipopolysaccharides in Pseudomonas
      syringae strains].
AB  - Component composition of lipid A of Pseudomonas syringae pv. syringae 218 and P
      55, pv. syringae (holci) 8299, pv. phaseolicola 120a, pv. atrofaciens 2399 has
      been studied. The lipid A composition of all the strains studied includes 3
      hydroxydecanoic fatty acid (3-OH-C10:0), 2-hydroxydodecanoic (2-OH-C12:0), 3
      hydroxydodecanoic (3-OH-C12:0), dodecanoic (C12:0), hexadecanoic (C16:0),
      octadecanoioc (C18:0), hexadecenic (C16:1), octadecenic (C18:1) fatty acids. The
      carbohydrate part of the lipid A macromolecule of all strains after acid
      hydrolysis contains ethanolamine, phosphoethanolamine, glucosamine.

PMID- 8563946
TI  - [The sorption of human and animal rotaviruses by Enterosgel].
AB  - Adsorptive activity of enterosgel has been studied as applied to different
      strains of rotaviruses of man and animals. Optimal amounts of the sorbent and pH
      values of the reaction medium at which rotaviruses were most efficiently sorbed
      from the virus-containing liquid were determined experimentally.

PMID- 8563947
TI  - [The types of interaction of the microflora of the human oropharynx with the
      causative agent of meningococcal infection].
AB  - It is shown that interrelationships between meningococci and positive symbionts
      can manifest themselves more often in the type of mutual or one-side regulatory
      reduction of intensity of the associates' growth and career they are displayed in
      stimulation of the development of pathogenic Neisseria populations.
      Representatives of three streptococci species (Streptococcus pyogenes, S. faecium
      and S. faecalis) are the most active antagonists in rate and strength of the
      suppressive effect in the simple and compound associations. The rest of the
      Corynebacteria and Staphylococci competitors in multicomponent associations show
      such properties career.

PMID- 8563948
TI  - [The species attribution of staphylococci isolated from patients with trichomonal
      urethritis].
AB  - Results of identification of 120 species of staphylococci isolated from
      trichomoniasis-suffering patients by means of the "staff-test" set of the Lachema
      firm are described. The test permits identifying 30 species of staphylococci. The
      author succeeded in identifying 8 species: Staphylococcus aureus, S.
      haemolyticus, S. intermedius, S. saprophiticus, S. capitis, S. hominis, S.
      warneri, S. epidermidis. It was impossible to identify specific belonging of 9
      strains. The following pathogenic properties were found: plasmocoagulase in
      58.33% of strains; anaerobic division of mannitol in 63.96%; lecithinase in
      63.06%; DNA-ase in 56.75%; urease in 89.18%; staphylotoxins alpha, beta, delta in
      84.68%, 61.26%, 94.59%, respectively. The sensitivity of staphylococci to
      antibiotics was different, S. saprophyticus was resistant to novobiocin.

PMID- 8563949
TI  - [Microbiological studies of stomatological periodontal films containing a
      derivative of chlorocinnamic aldehyde].
AB  - Stomatological parodontal films removing the effect of negative factors on the
      parodontal have been studied. Antibacterial effect of the derivative of
      chlorocinnamic aldehyde, composition ingredients and their different combinations
      as well as the films as a whole have been studied when creating stomatological
      parodontal films.

PMID- 8563950
TI  - [Immobilized microorganisms and water purification].
AB  - Advantages and disadvantages of cells of aerobic microorganisms immobilized by
      the type of adhesion and incorporation into the gel beads, the amount of retained
      biomass, limitations of diffusion of oxygen and nutrients, viability, morphology,
      biochemical properties are described. Immobilized biocatalysts are discussed in
      the aspect of their use in purification of sewage waters.

PMID- 8563951
TI  - A dialogue on compassion and supererogation in medicine.

PMID- 8563952
TI  - Physicians' duty of compassion.

PMID- 8563953
TI  - Love thy patient: justice, caring, and the doctor-patient relationship.

PMID- 8563955
TI  - Why it was hard for me to learn compassion as a third-year medical student.

PMID- 8563954
TI  - The relationship of empathy to moral reasoning in first-year medical students.

PMID- 8563956
TI  - Letting compassion open the door: battered women's disclosure to medical
      providers.

PMID- 8563957
TI  - Compassion, reason, and moral judgment.

PMID- 8563958
TI  - Sympathy as the basis of compassion.

PMID- 8563959
TI  - Illness and compassion: AIDS in an American Zen community.

PMID- 8563960
TI  - Richard Selzer on death, resurrection, and compassion. Interview by Thomasine
      Kushner.

PMID- 8563961
TI  - The Human Embryo Research Panel: lessons for public ethics.

PMID- 8563962
TI  - Can communities protect autonomy? Ethical dilemmas in HIV preventative drug
      trials.

PMID- 8563963
TI  - The limits of proxy decision making: overtreatment.

PMID- 8563964
TI  - A different kind of "prisoner's dilemma".

PMID- 8563965
TI  - VA network futility guidelines: a resource for decisions about withholding and
      withdrawing treatment.

PMID- 8563966
TI  - "Unexpected" death and other report cards on access and ethics.

PMID- 8563967
TI  - My father's choice.

PMID- 8563968
TI  - Dopamine--glutamate--GABA interactions and ageing: studies in the striatum of the
      conscious rat.
AB  - The effects of apomorphine, a D1-D2 dopamine receptor agonist, on the
      extracellular concentrations of glutamate and GABA were investigated in the
      striatum of young, middle-aged and aged rats. In vivo intracerebral perfusions
      were undertaken in the conscious rat using a concentric push-pull cannula system.
      Amino acid concentrations in samples were determined by HPLC with fluorometric
      detection. Apomorphine produced a concentration-related rise in striatal
      glutamate and GABA concentrations in young rats. Maximal increases were obtained
      at 20 microM apomorphine, and concentrations reached 184 and 191% of the basal
      value for glutamate and GABA respectively. Apomorphine failed to produce similar
      increases in glutamate concentration in middle-aged and aged rats. Apomorphine,
      at 10 microM, also failed to produce an increase in GABA concentration in the
      aged rats. However, at 20 microM apomorphine produced increases in GABA
      concentration in middle-aged and aged rats similar to those produced in young
      rats. These data are indicative of a change in threshold for GABA release induced
      by dopamine receptor stimulation in the aged rat. These results indicate that an
      interaction among dopamine, glutamate and GABA exists in the striatum of the rat,
      and that this type of interaction deteriorates with age.

PMID- 8563969
TI  - Immunohistochemical localization of five members of the Kv1 channel subunits:
      contrasting subcellular locations and neuron-specific co-localizations in rat
      brain.
AB  - A large variety of potassium channels is involved in regulating integration and
      transmission of electrical signals in the nervous system. Different types of
      neurons, therefore, require specific patterns of potassium channel subunits
      expression and specific regulation of subunit coassembly into heteromultimeric
      channels, as well as subunit-specific sorting and segregation. This was
      investigated by studying in detail the expression of six different alpha-subunits
      of voltage-gated potassium channels in the rat hippocampus, cerebellum, olfactory
      bulb and spinal cord, combining in situ hybridization and immunocytochemistry.
      Specific polyclonal antibodies were prepared for five alpha-subunits (Kv1.1,
      Kv1.2, Kv1.3 Kv1.4, Kv1.6) of the Shaker-related subfamily of rat Kv channels,
      which encode delayed-rectifier type and rapidly inactivating A-type potassium
      channels. Their distribution was compared to that of an A-type potassium channel
      (Kv3.4), belonging to the Shaw-related subfamily of rat Kv channels. Our results
      show that these Kv channel alpha-subunits are differentially expressed in rat
      brain neurons. We did not observe in various neurons a stereotypical distribution
      of Kv channel alpha-subunits to dendritic and axonal compartments, but a complex
      differential subcellular subunit distribution. The different Kv channel subunits
      are targeted either to presynaptic or to postsynaptic domains, depending on
      neuronal cell type. Thus, distinct combinations of Kv1 alpha-subunits are co
      localized in different neurons. The implications of these findings are that both
      differential expression and assembly as well as subcellular targeting of Kv
      channel alpha-subunits may contribute to Kv channel diversity and thereby to
      presynaptic and postsynaptic membrane excitability.

PMID- 8563970
TI  - Inertial, substratal and landmark cue control of hippocampal CA1 place cell
      activity.
AB  - Hippocampal 'place cells' discharge when a rat occupies a location that is fixed
      in relation to environmental landmarks. A principal goal of this study was to
      determine whether hippocampal place cell activity could be influenced by inertial
      cues. Water-deprived rats were trained in a square-walled open field in a dark
      room. The behavioral task required alternating visits to water reservoirs in the
      centre and in the four corners of the arena. The rat and arena were rotated in
      total darkness through +/-90, 180 or 270 degrees C. The next water reward was
      then presented in the corner at the same position relative to the outside room as
      before the rotation. A cue card was later illuminated in this corner as a visual
      cue for the extra-arena (room) reference frame. Fifteen out of 97 recorded
      hippocampal CA1 complex spike cells had spatially selective discharges in non
      central parts of the arena. After arena rotations, the firing fields of three
      units shifted between corners of the arena to maintain a fixed orientation
      relative to the room. This indicates that the hippocampus updated its
      representation of the position and heading direction of the rat using vestibular
      derived inputs concerning rotation angle. Other spatially selective discharges
      were guided to landmark cues (cue card or position of the reward: two units) or
      arena-locked 'substratal' cues (eight units). In six cells, place cell activity
      suddenly ceased or appeared following rotations. These results provide evidence
      for contributions of inertial as well as substratal and landmark information to
      hippocampal spatial representations.

PMID- 8563971
TI  - Targeted delivery of nerve growth factor via fibronectin conduits assists nerve
      regeneration in control and diabetic rats.
AB  - This study examined the influence of fibronectin conduits joining two halves of a
      sectioned sciatic nerve, with and without preimpregnation with nerve growth
      factor, on regeneration in rats with streptozotocin-induced diabetes mellitus.
      Regeneration, measured morphometrically in fibres containing immunoreactivity to
      calcitonin gene-related peptide (CGRP) and GAP-43, was significantly less (P <
      0.0001 for all comparisons) in diabetic rats with fibronectin mat grafts without
      nerve growth factor compared to similarly treated controls. Regeneration
      distances in diabetic rats were reduced to 43% (CGRP-reactive fibres) and 44%
      (GAP-43-reactive fibres) of controls, and the total amounts of immunoreactivities
      in the conduits were also reduced, though by lesser amounts (55 and 61% of
      controls respectively). Impregnation of the conduits with nerve growth factor
      before implantation increased the distance and amounts of regenerating
      immunoreactivity in both control and diabetic rats for both CGRP and GAP-43, such
      that these regeneration parameters were similar in nerve growth factor-treated
      diabetic rats to those in control rats implanted with untreated fibronectin mat
      conduits. These findings implicate impaired neurotrophic support in the defective
      regeneration characteristic of diabetic. neuropathy.

PMID- 8563972
TI  - NADPH diaphorase expression in the rat retina after axotomy--a supportive role
      for nitric oxide.
AB  - The large majority of mammalian retinal ganglion cells degenerate following
      section of their axons in the optic nerve. It has been suggested that some
      axotomized retina ganglion cells die because of toxic agents produced within
      their immediate environment. Our hypothesis was that nitric oxide might be one of
      the toxic factors implicated in the death of adult retinal ganglion cells post
      axotomy. In the first instance, we determined whether there were any changes in
      the retinal expression of NADPH diaphorase both 3 and 14 days following
      intraorbital section of the optic nerve in adult rats. Secondly, if nitric oxide
      was indeed implicated in the death of ganglion cells, then trophic factors which
      rescue these neurons might do so by decreasing the expression of nitric oxide
      synthase. Recently, we found that a collicular proteoglycan purified from the
      major target of retinal ganglion cells, the superior colliculus, rescued a
      greater proportion of adult ganglion cells from axotomy-induced death than most
      other known trophic factors. We thus injected this proteoglycan intraocularly
      after section of the optic nerve and examined its effect on the expression of
      NADPH diaphorase in the retina. Thirdly, an inhibitor of nitric oxide synthetase
      was repeatedly injected into the eye following the section of the optic nerve in
      order to determine if such a treatment might improve the survival of retinal
      ganglion cells. The present results indicate that section of the optic nerve does
      not alter the overall levels of NADPH diaphorase within the adult rat retina.
      Intraocular injections of the collicular proteoglycan actually increased the
      number of neurons expressing NADPH diaphorase, particularly in the ganglion cell
      layer. Finally, inhibition of nitric oxide synthetase following axotomy resulted
      in increased loss of retinal ganglion cells over a 2 week period when compared
      with controls. Our findings indicate that, rather than being toxic, small amounts
      of nitric oxide may be important for the survival of a proportion of injured
      retina ganglion cells.

PMID- 8563973
TI  - The nitric oxide/cGMP system in the antennal lobe of Apis mellifera is implicated
      in integrative processing of chemosensory stimuli.
AB  - The high concentration and the localization of nitric oxide synthase in the
      olfactory system of both vertebrates and invertebrates suggest that the
      diffusible messenger nitric oxide plays a central role in the processing of
      chemosensory information. This paper describes the nitric oxide releasing system
      in the antenna and the antennal lobes of Apis mellifera using the NADPH
      diaphorase technique, and analyses the contribution of the nitric oxide system in
      the neuronal processing of chemosensory signals using a behavioral assay in vivo.
      In the antenna the strongest NADPH diaphorase staining is found in non-neuronal
      auxiliary and/or epithelial cells, while the sensory cells and the antennal nerve
      are stained at a low level. At the major site of chemosensory signal integration,
      the antennal lobes, the highest nitric oxide synthase activity is located in the
      glomeruli, which are ideally suited to act as diffusion compartments. We
      demonstrate that inhibition of nitric oxide synthase in the antennal lobes
      specifically interferes with neuronal processing of repetitive chemosensory
      stimuli but does not affect the response to single stimuli, and is independent of
      parameters such as satiation level, stimulus strength, interstimulus interval and
      duration of sensory stimuli. Since inhibition of the soluble guanylate cyclase, a
      major target of nitric oxide, also particularly affects the adaptive component,
      the physiological effects of nitric oxide appear to be mediated by the action of
      cGMP. These findings suggest that the nitric oxide/cGMP system in the antennal
      lobes is a component of the molecular machinery involved in adaptive and/or
      integrative mechanisms during chemosensory information processing in vivo.

PMID- 8563974
TI  - BC1 RNA and vasopressin mRNA in rat neurohypophysis: axonal compartmentalization
      and differential regulation during dehydration and rehydration.
AB  - Brain cytoplasmic 1 (BC1) RNA is a small non-translated RNA polymerase III
      transcript. Because this RNA can be detected in the rat posterior pituitary with
      35S in situ hybridization autoradiography, it has been hypothesized that this RNA
      might be transported in the axons of hypothalamo-neurohypophyseal neurons. In the
      present study, we aimed to determine the cellular localization of BC1 more
      precisely by using non-radioactive in situ hybridization of BC1 RNA at both the
      light and electron microscopic levels. Our studies revealed that BC1 RNA was
      indeed located intra-axonally. Furthermore, BC1 RNA was abundant within a subset
      of axonal swellings and/or terminals, and was also found in discrete cytoplasmic
      domains of undilated axonal segments. Using a semiquantitative in situ
      hybridization approach, we have measured and compared the changes in BC1 RNA and
      arginine vasopressin (AVP) mRNA during dehydration (chronic salt-loading) and
      rehydration. Chronic salt-loading significantly increased both BC1 RNA and AVP
      mRNA. The increase in BC1 RNA labelling (2.5-fold), however, was modest and
      somewhat less enduring than the increase in AVP mRNA labelling (13-fold). Upon
      rehydration, both the BC1 and vasopressin transcripts in the posterior pituitary
      rapidly returned to control values. In conclusion, like vasopressin mRNA, BC1 RNA
      is transported in axons of the hypothalamo-neurohypophyseal system where it
      aggregates in a subset of axonal swellings, and its axonal transport is similarly
      regulated. Therefore, we propose that BC1 RNA might be involved in the axonal
      targeting, docking and/or transport of AVP or other axonal mRNAs.

PMID- 8563975
TI  - Lesions of the superior temporal cortical motion areas impair speed
      discrimination in the macaque monkey.
AB  - The effects of circumscribed lesions of the superior temporal cortical motion
      areas on speed discrimination were tested in three macaque monkeys using both
      moving random-textured patterns and moving bars. The lesions, which included the
      middle temporal visual area, the adjacent medial superior temporal visual area
      and the fundus superior temporal visual area, produced a severe and lasting
      deficit in speed discrimination when tested with the random patterns. In
      contrast, deficits were smaller when tested with moving bars. Control lesions of
      the inferior temporal cortex in two monkeys had little effect on speed
      discrimination. There was no clear deficit following inferior temporal or
      superior temporal sulcus lesions on a vernier acuity task. These experiments
      indicate that the middle temporal and adjacent areas play a crucial role in speed
      discrimination and that lesion effects depend on the cues available to the
      animals.

PMID- 8563976
TI  - Muller glia stabilizes cell columns during retinal development: lateral cell
      migration but not neuropil growth is inhibited in mixed chick-quail
      retinospheroids.
AB  - Radial columnar organization of cell clones is a characteristic feature of
      vertebrate retinae that is structurally not understood. Here we provide in vitro
      evidence that Muller glia processes stabilize cells within columns. Dissociated
      embryonic chick retinal plus pigmented cells regenerate in vitro into fully
      laminated stratospheroids. After reaggregating chick and quail cells, quail
      derived spheroid areas are detected as isolated sectors, as shown by a quail
      specific antibody. Each sector contains one or multiple cell columns. The radial
      borders separating chick and quail sectors are fully congruent with the extension
      of 3A7-labelled Muller glia processes. While cell somata do not show any lateral
      interspecies mixing, quail-derived neuropil extends within the inner plexiform
      areas far into chick sectors. After selective damage of Muller cells by the
      gliotoxin DL-alpha-aminoadipic acid, the columnar organization is destabilized,
      as evidenced by a decrease in vimentin expression and by the migration of
      individual neurons out of their cell column. These data demonstrate that Muller
      cells actively stabilize cells within their columns, while neuritic growth is not
      hindered.

PMID- 8563977
TI  - HIV-1 envelope proteins gp120 and gp160 potentiate NMDA-induced [Ca2+]i increase,
      alter [Ca2+]i homeostasis and induce neurotoxicity in human embryonic neurons.
AB  - The envelope glycoprotein gp120 of the human immunodeficiency virus HIV-1 has
      been proposed to cause neuron death in developing murine hippocampal cultures and
      rat retinal ganglion cells. In the present study, cultured human embryonic
      cerebral and spinal neurons from 8- to 10-week-old embryos were used to study the
      neurotoxic effect of gp120 and gp160. Electrophysiological properties as well as
      N-methyl-D-aspartate (NMDA)-induced current were recorded from neurons maintained
      in culture for 10-30 days. Neither voltage-activated sodium or calcium currents
      nor NMDA-induced currents were affected by exposure of neurons to 250 pM gp120 or
      gp160. In contrast, when neurons were subjected to photometric measurements using
      the calcium dye indo-1 to monitor the intracellular free Ca2+ concentration
      ([Ca2+])i, gp120 and gp160 (20-250 pM) potentiated the large rises in [Ca2+]i
      induced by 50 microM NMDA. The potentiation of NMDA-induced Ca2+ responses
      required the presence of Ca2+ in the medium, and was abolished by the NMDA
      antagonist D-2-amino-5-phosphonovalerate (AP5) and the voltage-gated Ca2+ channel
      inhibitor nifedipine. Moreover, exposure of a subpopulation of spinal neurons
      (25% of the cells tested) to 20-250 pM gp120 or gp160 resulted in an increase in
      [Ca2+]i that followed three patterns: fluctuations not affected by AP5, a single
      peak, and the progressive and irreversible rise of [Ca2+]i. The neurotoxicity of
      picomolar doses of gp120 and gp160 cultures was estimated by immunofluorescence
      and colorimetric assay. Treatment of cultures with AP5 or nifedipine reduced
      gp120-induced toxicity by 70 and

PMID- 8563978
TI  - Distribution of GLP-1 binding sites in the rat brain: evidence that exendin-4 is
      a ligand of brain GLP-1 binding sites.
AB  - The distribution and biochemical properties of glucagon-like peptide (GLP)-1(7
      36) amide (GLP-1) binding sites in the rat brain were investigated. By receptor
      autoradiography of tissue sections, the highest densities of [125I]GLP-1 binding
      sites were identified in the lateral septum, the subfornical organ (SFO), the
      thalamus, the hypothalamus, the interpenduncular nucleus, the posterodorsal
      tegmental nucleus, the area postrema (AP), the inferior olive and the nucleus of
      the solitary tract (NTS). Binding studies with [125I][Tyr39] exendin-4, a GLP-1
      receptor agonist, showed an identical distribution pattern of binding sites.
      Binding specificity and affinity was investigated using sections of the brainstem
      containing the NTS. Binding of [125I]GLP-1 to the NTS was inhibited concentration
      dependently by unlabelled GLP-1 and [Tyr39]exendin-4 with KI values of 3.5 and
      9.4 nM respectively. Cross-linking of hypothalamic membranes with [125I]GLP-1 or
      [125I][Tyr39]exendin-4 identified a single ligand-binding protein complex with a
      molecular mass of 63,000 Da. The fact that no GLP-1 binding sites were detected
      in the cortex but that they were detected in the phylogenetically oldest parts of
      the brain emphasizes that GLP-1 may be involved in the regulation of vital
      functions. In conclusion, the biochemical data support the idea that the central
      GLP-1 receptor resembles the peripheral GLP-1 receptor. Furthermore, the presence
      of GLP-1 binding sites in the circumventricular organs suggests that these may be
      receptors which act as the target for both peripheral blood-borne GLP-1 and GLP-1
      in the nervous system.

PMID- 8563979
TI  - Nucleus reticularis thalami and neocortical paroxysms in the rat.
AB  - The role of the nucleus reticularis thalami in spike-wave discharges in rats with
      genetic absence epilepsy has already been demonstrated. This study further
      investigated the role of the nucleus reticularis thalami in paroxysmal
      synchronizations in Sprague-Dawley rats; this strain shows no propensity to
      epileptic activity. Electroencephalographic patterns were followed in chronically
      implanted, unrestrained rats. After both electrolytic and chemical unilateral
      lesions, stereotaxically placed in the anterolateral sectors of this nucleus
      (verified post mortem), abnormal electroencephalographic rhythms (high-voltage
      polyspikes and spike-wave complexes) were recorded from the frontoparietal
      cortex, primarily in the contralateral hemisphere. Stereotyped discharges at 3 Hz
      developed progressively from multiple spikes within the alpha frequency range
      through the lengthening of the wave component. The excessive synchronized
      activity recorded from the intact hemisphere was of greater amplitude and
      occurred slightly earlier than from the lesioned hemisphere. These EEG patterns
      were associated with behavioural manifestations closely resembling those seen
      during absence seizures in humans. Bilateral lesions did not induce paroxysmal
      activity, both hemispheres being characterized by dominant delta/theta activity
      without signs of EEG-synchronized sleep. The seizures may thus have been due to
      disinhibition of the contralateral reticularis nucleus, recently shown to project
      to the reticularis nucleus of the other side in rats. This working hypothesis is
      supported by callosal cuts. The results indicate that the reticular neurons exert
      a control over neocortical paroxysmal activity even in animals which do not
      present genetic absence epilepsy.

PMID- 8563980
TI  - Receptive field properties of starburst cholinergic amacrine cells in the rabbit
      retina.
AB  - Patch-clamp recordings were made from ON starburst cholinergic amacrine cells
      with somas located in the ganglion cell layer of an isolated, dark-adapted rabbit
      retina preparation. Light responses were analysed and cell identify was confirmed
      anatomically. The centre light response had a linear current-voltage relation
      with a reversal potential close to 0 mV. The receptive field size was similar to
      the dendritic field size. Cholinergic amacrine cells displayed significant
      surround inhibition. The receptive field profile consisted of a central
      excitatory region flanked by an inhibitory surround. The surround attenuated the
      central response to 36% of the maximum. The surround was probably mediated by a
      combination of presynaptic and postsynaptic inhibition. Starburst amacrine cells
      did not display action potentials and the presence of a large, voltage-dependent
      outward current limited depolarizing responses to a maximum potential of about 
      40 mV. Light responses were completely suppressed during application of 100
      microM D,L-2-amino-4-phosphonobutyric acid (APB), consistent with activation
      exclusively through rod bipolar cells (on) and ON-cone bipolar cells. In darkness
      the cells displayed a tonic inward current that could be blocked by 100 microM
      APB and 2 microM CNQX.

PMID- 8563981
TI  - Postsynaptic targets of Purkinje cell terminals in the cerebellar and vestibular
      nuclei of the rat.
AB  - The cerebellar and vestibular nuclei consist of a heterogeneous group of
      inhibitory and excitatory neurons. A major proportion of the inhibitory neurons
      provides a GABAergic feedback to the inferior olive, while the excitatory neurons
      exert more direct effects on motor control via non-olivary structures. At present
      is is not clear whether Purkinje cells innervate all types of neurons in the
      cerebellar and vestibular nuclei or whether an individual Purkinje cell axon can
      innervate different types of neurons. In the present study, we studied the
      postsynaptic targets of Purkinje cell axons in the rat using a combination of pre
      embedding immunolabelling of the Purkinje cell terminals by L7, a Purkinje cell
      specific marker, and postembedding GABA and glycine immunocytochemistry. In the
      cerebellar nuclei, vestibular nuclei and nucleus prepositus hypoglossi Purkinje
      cell terminals were found apposed to GABAergic and glycinergic neurons as well as
      to larger non-GABAergic, non-glycinergic neurons. In the cerebellar and
      vestibular nuclei individual Purkinje cell terminals innervated both the
      inhibitory and excitatory neurons. Both types of neurons were contacted no only
      by non-GABAergic Purkinje cell terminals but also by GABA-containing terminals
      that were not labelled for L7 and by non-GABAergic, non-glycinergic terminals
      that formed excitatory synapses. Glycine-containing terminals were relatively
      scarce ( < 2% of the GABA-containing terminals) and frequently contacted the
      larger non-GABAergic, non-glycinergic neurons. To summarize, Purkinje cell axons
      evoke their effects through different types of neurons present in the cerebellar
      and vestibular nuclear complex. The observation that individual Purkinje cells
      can innervate both excitatory and inhibitory neurons suggests that the excitatory
      cerebellar output system and the inhibitory feedback to the inferior olive are
      controlled simultaneously.

PMID- 8563982
TI  - Morphine withdrawal syndrome and G protein expression: a study of the time course
      in the rat central nervous system.
AB  - We followed the changes in G protein alpha subunit expression and levels
      throughout the brain during the naltrexone-precipitated withdrawal syndrome in
      morphine-dependent rats. Intraperitoneally injected naltrexone (10 mg/kg) in rats
      made tolerant to morphine resulted in sustained withdrawal. Additional naltrexone
      doses 6, 24 and 72 h later still induced a significant abstinence syndrome. At
      the fifth naltrexone injection (8 days later) counted signs were completely
      resolved but checked ones were not. Besides the behavioural modifications, opiate
      withdrawal affected G protein expression in the central nervous system. In situ
      hybridization showed that G alpha s and G alpha o mRNA, whose levels are
      increased in tolerance, changed further during opiate withdrawal. Specifically,
      as alpha s mRNA in the hypothalamus was reduced after the first naltrexone
      injection and reached the control level with subsequent doses. However, alpha a
      mRNA expression in the olfactory system remained elevated after repeated
      naltrexone injections, declining to the control value of only after the fifth
      dose. The amounts of G alpha s and G alpha o protein closely followed the time
      course of mRNA. The relationship between behavioural and biochemical parameters
      is discussed, together with the regional selectivity of the modifications.

PMID- 8563983
TI  - Purification of a meningeal cell-derived chondroitin sulphate proteoglycan with
      neurotrophic activity for brain neurons and its identification as biglycan.
AB  - Serum-free cultures of meningeal fibroblasts synthesize and release a chondroitin
      sulphate proteoglycan (CSPG) that markedly enhances survival but not adhesion of
      embryonic rat (embryonic day 15) neocortical neurons in vitro. The active
      molecule was purified from conditioned medium (meningeal cell-conditioned medium,
      MCM) in three steps by means of fast-performance liquid chromatography
      fractionation combined with a quantitative microphotometric bioassay: (i)
      preparative Q-Sepharose anion exchange chromatography under native conditions;
      (ii) rechromatography of biologically active Q-Sepharose fractions on a MonoQ
      column in the presence of 8 M urea; and (iii) final gel filtration of active
      MonoQ fractions on Superose 6 in the presence of 4 M guanidinium hydrochloride.
      Analytical sodium dodecyl sulphate-polyacrylamide gradient gel electrophoresis of
      active Superose 6 fractions revealed a single broad glycoprotein band with a
      molecular mass in the range of 220-340 kDa. Further characterization of the
      purified molecule with glycosaminoglycan:lyases revealed a core protein of 50 kDa
      and the nearly complete loss of neurotrophic activity after chondroitinase
      digestion, whereas heparitinase treatment changed neither electrophoretic
      mobility nor biological activity. Amino-terminal sequencing of the purified CSPG
      core protein revealed identity with the amino acid sequence of rat biglycan.
      Biglycan purified from bovine cartilage supported neuron survival with virtually
      the same activity as the CSPG purified from MCM (half-maximal activity
      approximate to 10(-8) M). In conclusion, we isolated a neurotrophic CSPG from
      meningeal cells with strong survival-enhancing activity for brain neurons that
      was identified as biglycan, a molecule not previously related to neural
      functions.

PMID- 8563984
TI  - Actions of glycine on non-dopaminergic neurons of the rat substantia nigra.
AB  - The effects of glycine on non-dopaminergic cells in rat substantia nigra pars
      compacta and pars reticulata maintained in vitro were investigated using
      intracellular recording techniques. Glycine, superfused at a concentration
      between 30 microM and 1 mM, reversibly blocked the spontaneous firing of these
      neurons. The inhibition of firing discharge was associated with a
      hyperpolarization of the membrane (potassium acetate-filled electrodes) and an
      increase in conductance. Under voltage-clamp experiments (holding potential
      between -57 and -65 mV), glycine produced an outward response which reversed
      polarity at about -74 mV. However, when the recording electrodes were filled with
      KCl, the glycinergic response was mainly depolarizing/inward and reversed at
      about -43 mV. Thus, it appeared to be due to an increase in chloride
      permeability. Furthermore, the effects of glycine were reversibly antagonized by
      strychnine (between 300 nM and 1 microM). Our findings demonstrate that glycine
      is a potent inhibitory agent on non-dopaminergic cells of the substantia pars
      compacta and par reticulata that acts by activating strychnine-sensitive
      receptors.

PMID- 8563985
TI  - New ideas and their acceptance. As it has related to preservation of chordae
      tendinea and certain other discoveries.
AB  - The significant benefits of preserving chordal-papillary muscle integrity in
      mitral valve replacement took some two decades to become widely accepted.
      Familiarity with history clearly tells us that this paradox between our
      dedication to "new ideas" on the one hand, and opposition to their acceptance on
      the other has existed for hundreds of years. Most "new ideas" have been
      surrounded by controversy and opposition before wide acceptance. Selected
      examples from history are cited beginning with Roger Bacon in the 13th century,
      and continuing with Galileo, Semmelweiss, Lister, and Forssmann. The author cites
      two notable examples from his personal experiences. They occurred during the
      development of open heart surgery, and another during the development of the
      rigid bileaflet cardiac prosthesis, now known as the St. Jude cardiac prosthesis.
      Some of the basic reasons for this inevitable opposition are: an innate
      skepticism over anything "new." Simplicity is often resented, as well as any need
      to change patterns of behavior/habits. Determination, persistence, stubbornness
      are the most important components for successful research. In addition, the
      successful innovator must learn to expect opposition and not be deterred by it,
      but rather must learn to take sustenance from it, and "learn to thrive upon
      opposition." In conclusion, these observations and suggestions are summarized in
      a satire on "The Seven Ages in the Evolution of an Idea--with particular
      reference to the critic."

PMID- 8563986
TI  - Left ventricular function in valvular heart disease. Workshop proceedings.
      London, 30 March-1 April 1995.

PMID- 8563987
TI  - Preservation of papillary muscles and chordae during mitral valve replacement:
      possibilities and limitations.
AB  - The various techniques of preserving the chordal apparatus in mitral valve
      replacement applied in 1,453 cases at a single institution between 1986 and 1994
      are described. The techniques include preservation of chordal attachment to the
      posterior mitral leaflet only and to both leaflets with five different technical
      variations. The specific advantages and risks of these techniques are
      demonstrated and discussed. It is concluded, that preservation of the entire
      subvalvular structures is feasible in almost all cases. Different procedures
      should be employed according to the variety of mitral disease, in particular with
      respect to mitral leaflet mobility.

PMID- 8563988
TI  - Mitral valve procedures in ischemic regurgitation.
AB  - A restrictive definition of ischemic mitral regurgitation (IMR) has allowed us to
      select a more uniform cohort of 41 patients having undergone mitral valve surgery
      for IMR between January 1993 and March 1995. Thirty-six patients (88%) presented
      with chronic and five with acute IMR. All patients had at least one significant
      stenosis in the circumflex area. Left ventricular ejection fraction averaged 35%.
      Transesophageal echocardiography (TEE) revealed a > or = 3+ MR in 30 patients and
      an intermittent, fluctuating or grade 2+ MR in 11 (27%). Annulus dilatation was
      found in all cases, and it was the only mechanism in 10 (24.4%). Leaflet
      restrictive motion was clearly seen in 17 cases (41.5%) and leaflet prolapse in
      14 (34%). In doubtful cases, an intra-operative dynamic testing using TEE, and
      associating a loading test and an afterload test, led to the indication of a
      valve procedure in 11/19 patients (58%). An average of three distal coronary
      anastomoses per patient were constructed. Mitral valve replacement (MVR) was
      unavoidable in four patients (9.8%); at least the posterior leaflet subvalvular
      apparatus was preserved in all. Repair of the mitral valve (Mvrep) was achieved
      in 37 cases (90%). Ring annuloplasty alone was performed in 27 cases (73%). In
      the remaining 10 cases, leaflet prolapse was corrected by various artifices such
      as flip-over technique, quadrangular resection, papillary muscle plication or
      commissuroplasty. At the 10th postoperative day, a residual MR was found in 4/34
      cases (11.8%), only after isolated ring annuloplasty. The four patients who have
      died in the ICU after MVrep belonged to the same group of isolated ring
      annuloplasty; this mortality of 4/27 (14.8%) illustrates the mediocre prognosis
      of marked annulus dilatation and impaired LV function with restrictive leaflet
      motion. Overall, the hospital mortality (14.6%) more reflected the mode of
      presentation of the patients than the type of operative technique: when a short
      and definitive procedure is required by a precarious general condition, one
      should not hesitate to prefer a rapid MVR to a complicated repair. At 4.5 months,
      there was no significant improvement in LV dimensions. At six months, 80.5% of
      the patients survived, with 88% of them being in NYHA class I or II.

PMID- 8563989
TI  - The relationship of left ventricular geometry and hypertrophy to left ventricular
      function in valvular heart disease.
AB  - Valvular heart disease imposes a hemodynamic load on the left or right ventricle.
      This load is compensated by the development of ventricular hypertrophy. The
      pattern of hypertrophy which develops is characteristic of each type of valvular
      lesion with concentric hypertrophy compensating the pressure overload of aortic
      stenosis, eccentric hypertrophy compensating the volume overload of mitral
      regurgitation and both concentric and eccentric hypertrophy compensating the
      combined pressure and volume overload of aortic regurgitation. While these
      patterns are characteristic, there is substantial variation in the geometric
      distribution of hypertrophy among individuals with the same valvular disease.
      This variability in turn produces variability in the amount of compensation from
      patient to patient. The geometric pattern of hypertrophy which develops primarily
      affects left ventricular function as it relates to the Laplace equation. An
      increase in the radius to thickness ratio increases wall stress while a decrease
      in this ratio decreases wall stress. Discussed below are the mechanisms by which
      the various geometries that develop in valvular heart disease affect loading to
      become adaptive or maladaptive or both.

PMID- 8563990
TI  - Left ventricular function in valvular heart disease: invasive and non-invasive
      assessment of left ventricular function.

PMID- 8563991
TI  - The effect of left ventricular function on the echocardiographic assessment of
      heart valve disease.
AB  - Transvalvar velocities or derived pressure differences are highly dependent on
      flow. They must be corrected for flow for research studies or in the clinical
      situation where values are intermediate and difficult to interpret. This can be
      done using the continuity equation or using formulae based on ratios of mean
      pressure drop and flow of which resistance is probably more accurate than the
      Gorlin formula. Left ventricular diastolic behavior is a major determinant of
      mitral pressure half-time where the mitral stenosis is mild and also of the slope
      of the continuous wave recording in mild or moderate aortic regurgitation.
      Methods for assessing mitral regurgitation including patterns of pulmonary vein
      flow are also dependent on left ventricular function. The echocardiographic
      methods of describing valve function cannot be interpreted without regard to left
      ventricular function and loading conditions.

PMID- 8563992
TI  - Biological characteristics of the myocardium during the regression of cardiac
      hypertrophy due to mechanical overload.

PMID- 8563993
TI  - The effect of left ventricular systolic function on long term survival in mitral
      and aortic regurgitation.
AB  - To identify the predictive factors of left ventricular dysfunction (LVD) after
      surgery, we performed an uni- and multivariate analysis of the data concerning
      286 patients operated for pure aortic regurgitation between 1980 and 1994 and 460
      patients operated for pure non-ischemic mitral regurgitation over a period of 24
      years. Among the aortic regurgitation patients, 28 developed left ventricular
      dysfunction not attributable to residual aortic valve dysfunction, another
      valvular lesion or hypertensive or ischemic heart disease. By univariate analysis
      identified predictive factors of LVD were duration of symptoms prior to surgery,
      duration of the history of diastolic murmur, NYHA class, cardiothoracic ratio, LV
      echographic diameters, fractional shortening of short axis, LV end-systolic
      volume and LV ejection fraction. Multivariate analysis identified three
      independent predictors: NYHA functional class, LV end-systolic diameter and LV
      ejection fraction. Of 428 operative survivors with non-ischemic mitral
      regurgitation 63 developed severe LVD. Univariate analysis identified functional
      class III or IV, duration of symptoms prior to surgery, atrial fibrillation, echo
      LV and LA diameters, angio LV volumes, LV ejection fraction, cardiac index and
      type of surgery as independent predictors of LVD. Multivariate analysis showed
      that type of surgery, LV ejection fraction, LV end-diastolic and end-systolic
      volume and echo LV end-systolic diameter were all independent predictors of LVD.

PMID- 8563994
TI  - Medical treatment of chronic valvular regurgitation.

PMID- 8563995
TI  - Left ventricular function after mitral valve surgery.
AB  - This study examined the effects of various operative procedures on the mitral
      valve of patients with mitral regurgitation due to degenerative disease of the
      mitral valve. A randomized clinical trial on the type of annuloplasty ring used
      at surgery revealed that early postoperative left ventricular systolic function
      was better in patients who had a flexible ring than in patients who had a rigid
      ring. Two years after surgery there were no differences between these groups and
      most patients were found to have fairly normal left ventricular function. The
      long term results of mitral valve repair in 184 patients revealed a 10-year
      actuarial survival of 86% +/- 6%. A randomized trial on the effect of
      preservation of chordae tendineae during mitral valve replacement revealed that
      the beneficial effect of this procedure on left ventricular function is a lasting
      one; five years after surgery patients who had mitral valve replacement with
      preservation of the chordae tendineae have better exercise capacity, and better
      left ventricular systolic function and performance. The long term results of
      mitral valve replacement in 154 patients revealed a 10-year actuarial survival of
      69% +/- 5%. Logistic regression analysis indicated that age greater than 65 years
      and complete excision of the native mitral valve were predictors of late
      mortality. Of those patients, 70 had had chordal preservation during surgery and
      84 did not. These two subgroups were remarkably similar preoperatively, but the
      10-year actuarial survival was 80% +/- 6% for patients who had chordal
      preservation and 63% +/- 6% for those who did not. The mitral valve should be
      repaired whenever possible; if replacement is necessary it should be performed
      with preservation of the chordae tendineae.

PMID- 8563996
TI  - Left ventricular function after mitral valve replacement with or without chordal
      preservation.
AB  - The clinical significance of the chordae tendinae regarding postoperative left
      ventricular performance was evaluated in 148 patients with mitral regurgitation
      or mitral stenosis who underwent either mitral valve replacement using St. Jude
      Medical valve with complete chordal preservation, or with conventional mitral
      valve replacement, or valve repair. Mitral valve replacement preserving the
      autologous chordae tendinae (n = 28) or replacing them with Gore-Tex sutures (n =
      16) was performed in 44 patients, 24 with mitral regurgitation and 20 with mitral
      stenosis. Their hemodynamic parameters were compared to those of patients who
      underwent conventional mitral valve replacement involving 25 with mitral
      regurgitation and 28 with mitral stenosis, or who underwent valve repair in 24
      with mitral regurgitation, or commissurotomy in 27 patients with mitral stenosis.
      The LV performance was analyzed by cineangiography in the early (mean 1.2
      months), and by multiple gated blood scintigraphy (MUGA), or echocardiography
      (UCG) in the late postoperative periods (mean 5.4 years) in the three groups of
      patients. In the mitral regurgitation group, the LV ejection fraction (EF) was
      unchanged in the chordal preserved group, but it was decreased in the
      conventional replacement and repair groups. The LV contractility index was better
      in the chordal preserved than in the conventional group. Both the LVEF by MUGA,
      and LV fractional shortening (FS) by UCG were significantly higher after chordal
      preservation or repair than after conventional valve replacement. The chordal
      preserved group exhibited superior LV performance than the conventional group,
      especially in those with mitral regurgitation and depressed preoperative left
      ventricular function (EF < 0.50). There were no significant difference between
      the three groups in patients with mitral stenosis. The results support the
      concept that maintenance of continuity between the mitral annulus and the
      papillary muscle has a beneficial effect on postoperative left ventricular
      performance, especially in patients with mitral regurgitation and depressed
      preoperative left ventricular function, but had no major effect in patients with
      mitral stenosis.

PMID- 8563997
TI  - Left ventricular function in heart valve surgery: a multidisciplinary challenge.
AB  - Between January 1988 and December 1994, 4,097 patients underwent heart valve
      replacement at the Heart Center North Rhine-Westfalia, Bad Oeynhausen, 1,388
      (33.8%) of them suffered from impaired left ventricular (LV) function. Overall
      hospital mortality was 2.3% (n = 95). In the poor LV function group it was 1.8%
      (n = 25). There was a significant increase of mortality from 1.5% in patients
      younger than 60 years to 4.9% in patients 80 years of age and older. Reoperations
      and emergency operations showed an additional increase of mortality each: 6.2%
      and 18.2%, respectively. Medium term survival (maximum 48 months) was assessed in
      a group of 2,006 patients operated between January 1991 and December 1993. The
      cumulative mortality for patients with poor LV function (n = 148) was 12.8%,
      whereas for those with normal LV function it was 6.1%. Our data suggest that left
      ventricular function is of minor importance as far as primary operative results
      are concerned. In long term follow up patients with valve replacement and poor LV
      function show an increased mortality mainly due to cardiac causes.

PMID- 8563998
TI  - Integrated myocardial management in valvular heart disease.
AB  - This report describes the technique of Integrated Myocardial Management that
      combines the advantages of various cardioprotective strategies to compensate for
      their individual shortcomings. This approach co-ordinates the myocardial
      protective techniques with the continuity of the operation so that the surgical
      continuity of the procedure is never interrupted, and there is simultaneously (a)
      unimpaired vision, (b) avoidance of unnecessary ischemia and cardioplegic
      overdose, (c) aortic clamping as soon as cardiopulmonary bypass is started, (d)
      aortic unclamping and discontinuation of bypass very shortly after the technical
      procedure is completed, while (e) minimizing the duration of ischemia and
      cardiopulmonary bypass and (f) maximizing the positive attributes of the
      strategies available currently. The background for this myocardial management
      method that combines antegrade/retrograde delivery, warm/cold blood cardioplegia,
      intermittent/continuous perfusion, blood/blood cardioplegia, and avoidance of
      cardioplegic overdose, hemodilution, and tangential aortic clamping is discussed.
      The preliminary results in 394 consecutive patients from three centers where
      surgeons who participated in the infra-structure of this method is presented.
      This has led to our adoption of this approach in all adult cardiac operations.

PMID- 8563999
TI  - Torsional deformation of the left ventricle.

PMID- 8564000
TI  - Left ventricular function and valvular reoperations.
AB  - Between 1961 and 1994, 1,120 adult and adolescent patients had reintervention on
      the aortic, mitral or both valves. Operative mortality was 7%; five, 10, 15 and
      20 year survival rates were 81%, 65%, 54% and 52%, respectively. From the sixties
      to the nineties, the number of procedures (58 to 304), the age of patients (40 to
      57 years), incidence of acute endocarditis (0 to 9%), concomitant coronary
      surgery (0 to 13%) and the number of repeated interventions (5% to 22%) gradually
      increased. Despite such increasingly difficult conditions the operative mortality
      remained low and five-year survival acceptable during the last 20 years.
      Operative mortality was significantly higher in patients over 65 years (11% vs.
      5%), in cases with additional coronary surgery (16% vs. 5%) or interventions on
      the ascending aorta (17.5% vs. 5%). Left ventricular systolic function was
      quantitatively assessed before reoperation in 372 patients. In patients with
      stenotic mitral lesion or with aortic valvular lesion and additional surgical
      interventions reduced ejection fraction (< 50%) had no effect on late outcome. In
      regurgitant aortic and mitral lesions and interventions on both valves, there was
      a trend for less successful late outcome after reintervention, but the difference
      did not reach statistical significance. It is concluded that valvular
      reoperations can be performed nowadays with only slightly increased operative
      risk and an acceptable late outcome as compared to primary valvular operations.
      Hemodynamically significant valvular and/or prosthetic lesion should be corrected
      again without delay regardless of an impaired left ventricular function.

PMID- 8564001
TI  - Left ventricular function in aortic stenosis: a clinical review.

PMID- 8564002
TI  - Left ventricular function in mitral valve disease.

PMID- 8564003
TI  - Left atrial performance indices in chronic mitral valve disease.
AB  - Multidimensional left atrial (LA) performance indices have not been extensively
      studied in chronic mitral valve disease. LA maximal volume, stroke volume (LA
      volume at atrial systole minus LA minimal volume), LA ejection fraction (stroke
      volume/volume at atrial systole) and A-wave velocity, were measured in 14
      patients with mitral stenosis (mean mitral valve area 1.5 cm2); 14 patients with
      chronic mitral regurgitation all in sinus rhythm; and were compared to 20 age and
      sex matched normal control subjects using biplane transthoracic echo and pulsed
      Doppler. Although LA volumes--maximal and at onset of atrial systole--were
      greater in mitral regurgitation and mitral stenosis (p < 0.01) compared to normal
      subjects, LA ejection fraction was not statistically different among the three
      groups. LA stroke volume was greater in mitral regurgitation and mitral stenosis
      compared to normal subjects, p < 0.01. LA kinetic energy (LAKE) = 1/2 mv2 (m = LA
      stroke volume x 1.06, blood's specific gravity, v = A wave velocity) was
      increased in mitral stenosis and mitral regurgitation compared to normal subjects
      (p < 0.001). An inverse correlation (r = 0.66, p < 0.01) was present between LAKE
      and mitral valve area in mitral stenosis. It is concluded that LA function, a
      complex interplay of multiple factors, requires multidimensional methods of
      analysis beyond standard measurements of size and volume, which provide
      additional insight into normal LA function, and better definition of LA function
      changes involved in the natural history of chronic mitral valve disease.

PMID- 8564004
TI  - Artificial chordae.
AB  - One hundred and eighty-seven patients had mitral valve repair and 28 mitral valve
      replacement using 5-0 expanded polytetrafluoroethylene (e-PTFE). A mean of 6.7
      (range 2-24) artificial chordae were utilized in each patient, associated with an
      autologous pericardium reinforced suture annuloplasty in most cases. Six patients
      required mitral valve replacement during the same operation, and one after 48
      hours for unsatisfactory operative result. There was one operative death due to
      respiratory insufficiency. NO early valve-related complications were reported. At
      a mean follow up of 35.6 months (range 1-99 months), two more patients died
      because of cardiomyopathy and multi-organ failure, respectively, while only one
      patient experienced a TIA, returning to sinus rhythm two months after operation.
      Three patients required reoperation for rupture of natural chordae, traditionally
      shortened at operation in one case; for technical error in tying the artificial
      chordae in the second, and for progression of the degenerative disease in the
      third. At reoperation the artificial chordae appeared partially covered by a
      fibrous sheath, without any sign of thrombosis or calcification. Transesophageal
      echocardiography revealed a satisfactory long term result in 97% of the cases,
      while four patients showed a recurrence of mild mitral regurgitation, probably
      due to the progression of rheumatic valve pathology. Ninety-five percent of the
      patients are in NYHA class I. This surgical technique appears to be reproducible
      and reliable, improving the results of mitral valve repair, increasing the number
      of valves repaired, and optimizing left ventricular function in the case of
      mitral valve replacement with unavoidable removal of the entire subvalvular
      apparatus.

PMID- 8564005
TI  - Microsatellite variation in grey seals (Halichoerus grypus) shows evidence of
      genetic differentiation between two British breeding colonies.
AB  - Eight highly variable microsatellite loci were used to examine the genetic
      variability and differentiation of grey seals (Halichoerus grypus) at two widely
      spaced British breeding colonies. Samples were collected from adults and pups on
      the island of North Rona, off the north-west coast of Scotland, and on the Isle
      of May, situated at the mouth of the Firth of Forth on the east coast. Highly
      significant differences in allele frequencies between these two sites were found
      for all eight loci, indicating considerable genetic differentiation. Thus,
      although grey seals are known to range over very large areas outside the breeding
      season, site fidelity of adults and philopatry of pups for these breeding
      colonies must be sufficiently common to have effects, through genetic drift, at
      the sub-population level. Migration rate was estimated using Wright's fixation
      index (FST), Slatkin's private alleles model and the new statistic, RST, which is
      analogous to FST but which takes into account the process of microsatellite
      mutation. An almost 8-fold discrepancy between the values we obtained provides
      cautionary evidence that microsatellite loci may contravene one or more of the
      assumptions on which these methods are based.

PMID- 8564006
TI  - A PCR test for avian malaria in Hawaiian birds.
AB  - The decline of native Hawaiian forest birds since European contact is attributed
      to factors ranging from habitat destruction to interactions with introduced
      species. Remaining populations of Hawaiian honeycreepers (Fringillidae:
      Drepanidinae) are most abundant and diverse in high elevation refuges above the
      normal range of disease-carrying mosquitoes. Challenge experiments suggest that
      honeycreepers are highly susceptible to avian malaria (Plasmodium sp.) but
      resistance exists in some species. In order to detect low levels of malarial
      infection and quantify prevalence of Plasmodium in high elevation natural
      populations of Hawaiian birds, a polymerase chain reaction (PCR) based diagnostic
      test was developed that identifies rRNA genes of Plasmodium in avian blood
      samples. Quantitative competitive PCR (QC-PCR) experiments indicate that the
      detection limit of our test is an order of magnitude greater than that reported
      for human malaria DNA blot tests. Compared with standard histological methods,
      the PCR test detected a higher prevalence of diseased birds at mid-elevations.
      Malaria was detected in three species of native birds living in a high elevation
      wildlife refuge on the island of Hawaii and in four species from Maui. Our
      results show that avian malaria is more widespread in Hawaiian forests than
      previously thought, a finding that has important conservation implications for
      these threatened species.

PMID- 8564007
TI  - Genetic differentiation in Fomitopsis pinicola (Schwarts: Fr.) Karst studied by
      means of arbitrary primed-PCR.
AB  - Genetic variation within and among one Finnish and three Swedish populations of
      Fomitopsis pinicola (Schwarts: Fr.) Karst. were studied by amplifying DNA from
      haploid isolates originating from single spore cultures using two arbitrary
      primers. Analysis offspring from single fruit bodies revealed only three pairs of
      codominant alleles among 42 variable genetic markers, the remaining 38 segregated
      independently. Genetic similarity was measured in terms of Euclidean distance.
      Individuals in the Finnish population tended to form a distinct cluster in the
      principal component analysis. Variation within and among populations/regions was
      partitioned by Analysis of Molecular Variance-AMOVA. Within population variation
      accounted for 91.6% of the total genetic variation. The remaining 7.68% was
      accounted for by variation between the Finnish population and each of the three
      Swedish ones. Variation among the Swedish populations accounted for only 0.72% of
      the total variation. Wright's Fst was 0.17 for all four populations and 0.13 for
      the three Swedish populations. These relatively low values indicate that there is
      gene flow among all populations or that they are derived from a common ancestral
      population. The observed pattern of genetic variation is probably the result of
      effective spore dispersal and the continuous distribution of this common early
      successional species.

PMID- 8564008
TI  - A phylogeographic survey of brook charr (Salvelinus fontinalis) in Algonquin
      Park, Ontario based upon mitochondrial DNA variation.
AB  - Forty-nine populations of brook charr (Salvelinus fontinalis) from Algonquin Park
      lakes and rivers were analysed for mitochondrial DNA variation. Haplotypic
      distributions of wild fish in the Algonquin Park region of Ontario, Canada,
      predominantly reflect postglacial dispersal patterns into the region in spite of
      substantial hatchery plantings. Two major refugial groupings colonized this
      regions. Northern and eastern watersheds (Amable du Fond, Bonnechere, and
      northern Petawawa), were colonized primarily by haplotype 1 fish (B1 phylogenetic
      assemblage), while Oxtongue River, southern Petawawa, and York River populations
      were colonized predominately by fish from the B2 and A mtDNA phylogenetic
      assemblages. Fish with haplotypes in the A and B2 phylogenetic assemblages are
      common in the Lake Huron drainage. All watersheds in the Park drain into the
      Ottawa River, except the Oxtongue drainage (part of the Lake Huron watershed).
      This suggests that early glacial outflows south of the Algonquin Park region
      (Kirkfield-Trent) may have been colonized by fish that initially invaded 'Ontario
      island' (south-western Ontario), while fish which invaded northern Algonquin Park
      were derived from a different refugial grouping(s) which may have involved
      colonization both up the Ottawa River drainage, and/or from a more westerly
      (Mississippian) refugial grouping. A majority of the populations in Algonquin
      Park have been planted with hatchery reared brook charr since the 1940s. The
      Hills Lake or 'Domestic' strain was used almost exclusively for these plantings.
      Comparisons of mtDNA haplotypic distributions in hatchery and wild fish suggests
      that hatchery females had minimal spawning success and/or their progeny had poor
      survivorship in the wild.

PMID- 8564009
TI  - Intraspecific phylogeography of the gopher tortoise, Gopherus polyphemus: RFLP
      analysis of amplified mtDNA segments.
AB  - The slow rate of mtDNA evolution in turtles poses a limitation on the levels of
      intraspecific variation detectable by conventional restriction fragment surveys.
      We examined mtDNA variation in the gopher tortoise (Gopherus polyphemus) using an
      alternative restriction assay, one in which PCR-amplified segments of the
      mitochondrial genome were digested with tetranucleotide-site endonucleases.
      Restriction fragment polymorphisms representing four amplified regions were
      analysed to evaluate population genetic structure among 112 tortoises throughout
      the species' range. Thirty-six haplotypes were identified, and three major
      geographical assemblages (Eastern, Western, and Mid-Florida) were resolved by
      UPGMA and parsimony analyses. Eastern and Western assemblages abut near the
      Apalachicola drainage, whereas the Mid-Florida assemblage appears restricted to
      the Brooksville Ridge. The Eastern/Western assemblage boundary is remarkably
      congruent with phylogeographic profiles for eight additional species from the
      south-eastern U.S., representing both freshwater and terrestrial realms.

PMID- 8564011
TI  - Using chloroplast DNA to trace postglacial migration routes of oaks into Britain.
AB  - Postglacial migration is a major factor responsible for the patterns of genetic
      variation we see in natural populations. Fossil pollen data indicate that early
      postglacial colonists such as oak, were able to take both western and eastern
      migration routes into Britain. Analysis at a finer level is now permitted by the
      use of modern molecular techniques. A 13-bp duplication in the chloroplast
      tRNA(Leu1) intron occurs in natural populations of East Anglian oaks, but is not
      found in other parts of Britain or from mainland Europe. The distribution of this
      marker suggests that the mutation occurred either in southern England, or during
      migration from the mainland, and became fixed in a source population from which
      East Anglia was colonized. Planting of non-native trees for roadside boundaries
      and in the grounds of old houses and estates, explains the absence of the marker
      from some East Anglian oaks.

PMID- 8564010
TI  - Dynamics of Mhc evolution in birds and crocodilians: amplification of class II
      genes with degenerate primers.
AB  - Genes of the major histocompatibility complex (Mhc) are the most polymorphic
      functional loci in mammalian populations, but little is known of Mhc variability
      in natural populations of nonmammalian vertebrates. To help extend such studies
      to birds and relatives, we present a pair of degenerate primers that amplify
      polymorphic segments of one chain (the beta chain) of the class II genes from the
      major histocompatibility complex (Mhc) of archosaurs (birds+crocodilians). The
      primers target two conserved regions lying within portions of the antigen-binding
      site (ABS) encoded by the second exon and amplify multiple genes from both
      genomic DNA and cDNA. The pattern of nucleotide substitution in ABS codons of 51
      sequences amplified and cloned from five species of passerine birds and an
      alligator (Alligator mississippiensis) indicates that archosaurian class II beta
      genes are subject to selective forces similar to those operating in mammalian
      populations. Hybridization of a genomic clone generated by the primers revealed
      highly polymorphic bands in a sample of Florida scrub jays (Aphelocoma
      coerulescens coerulescens). Because the primers amplify only part of the ABS from
      multiple class II genes, they will be useful primarily for generating species
      specific clones, thereby providing a critical inroad to more detailed structural
      and evolutionary studies.

PMID- 8564012
TI  - Mitochondrial DNA variation and population genetic structure of the northern
      redbelly dace (Phoxinus eos).
AB  - Two sections of the control region and the genes coding for NADH dehydrogenase
      subunits 5 and 6 (ND-5/6) of mitochondrial DNA (mtDNA) were amplified from
      Phoxinus eos with the polymerase chain reaction. Both sections of the control
      region were sequenced directly while the ND-5/6 fragment was sequenced in from
      each end only. Additionally, the entire ND-5/6 fragment was examined for sequence
      variation using RFLP analysis. No sequence variation was detected in the control
      region among 70 individuals sampled from 18 populations across three Ontario
      regions (Spanish River, Madawaska R. and Cataraqui R.). To examine ND-5/6
      variation, a total of 75 individuals were sampled from five populations
      representing two of the three regions (Madawaska River and Cataraqui R.). Six
      haplotypes were detected by direct sequencing and four by RFLP analysis.
      Estimates of population subdivision from RFLP data, sequence analysis, and the
      two data sets combined for the ND-5/6 fragment, suggest that gene flow is
      restricted within and between regions. However, estimates of sequence divergence
      for both sequence and RFLP analysis of this fragment suggested that populations
      were either founded by already differentiated populations or that populations
      were founded by a single stock and divergence between regions occurred prior to
      isolation of populations within regions. These estimates of population structure
      are much greater than those obtained from allozyme analysis. Additionally, high
      levels of heterozygosity in nuclear DNA, but low mtDNA diversity suggests that
      populations have experienced reductions in population size sufficient to reduce
      only mtDNA variation. Random lineage extinction and limited time for the
      accumulation of new mutations are likely responsible for low levels of mtDNA
      variation in ND-5/6 and the control region, while functional constraints may
      limit variation more than expected in the control region in dace and other
      fishes.

PMID- 8564013
TI  - Site directed chromosomal marking of a fluorescent pseudomonad isolated from the
      phytosphere of sugar beet; stability and potential for marker gene transfer.
AB  - A plasmid-free, non-pathogenic, ribosomal RNA group 1 fluorescent pseudomonad,
      Pseudomonas fluorescens SBW25, was selected from the microflora of sugar beet
      (Beta vulgaris) and modified to contain constitutively expressed marker genes. By
      site directed homologous recombination a KX cassette [kanamycin resistance (kanr)
      and catechol 2,3 dioxygenase (xylE)] and a ZY cassette [lactose utilization
      (lacZY, beta-galactosidase, lactose permease)] were introduced at least 1 Mbp
      apart on the 6.6 Mbp bacterial chromosome. Separate sites were selected to
      provide sensitive detection methods and allow assessments of marker gene
      stability of the genetically modified micro-organism (GMM), SBW25EeZY6KX, when it
      colonized the leaves and roots of sugar beet plants following seed inoculation.

PMID- 8564014
TI  - Isolation and characterization of microsatellite loci in the goldfish Carassius
      auratus.

PMID- 8564015
TI  - Application of fluorescence spectroscopy for determining the structure and
      function of proteins.

PMID- 8564016
TI  - Fourier transform infrared spectroscopy investigations of protein structure.
AB  - Infrared spectroscopy can provide insight into protein structure. This technique
      is sensitive to the backbone amide arrangement of peptide and protein molecules.
      In many cases, complementary as well as more expansive information is obtained as
      opposed to information obtained by other methods that examine the molecule's
      environmental surroundings, require molecular probes, or perhaps cannot
      investigate the molecule in its native environment. The foundation for
      spectroscopic differences between the various secondary structures arises not
      only from geometrical differences and hydrogen bond variations but also
      transition dipole coupling between neighboring oscillators. Theoretical
      predictions of protein spectra have been made using normal mode analysis and
      combined with experimental data. At present the amide I band has provided the
      most insight into secondary structure. Even more convincing results are obtained
      when both H2O and D2O are used as solvents. Recent advances in computerized
      technology and mathematical techniques have expanded the potential contributions
      of infrared spectroscopy in the area of protein structural determination.
      However, the limitations of resolution enhancement and curve-fitting techniques
      must be taken into consideration. The parameters must be carefully and optimally
      chosen and evaluated on a case-by-case basis. The subjectivity of these
      techniques makes a thorough understanding of the algorithms necessary, especially
      those commercially available. Infrared spectroscopy continues to provide insight
      into protein and peptide structures under biologically relevant conditions that
      enable the structure-function relationships for such molecules to be better
      understood.

PMID- 8564017
TI  - Mass spectrometry in protein structural analysis.

PMID- 8564018
TI  - Two-, three-, and four-dimensional nuclear magnetic resonance spectroscopy of
      protein pharmaceuticals.
AB  - Advances in NMR spectroscopy and related computational methods continue at a
      rapid pace. In the past three years, the capability to make complete assignments
      of protein spectra has expanded from a limit of approximately 100 residues to a
      limit of possibly 400 residues via isotope-edited three- and four-dimensional
      methods.

PMID- 8564020
TI  - Chromatographic techniques for the characterization of proteins.

PMID- 8564019
TI  - Thermodynamic strategies for rational protein and drug design.

PMID- 8564021
TI  - Capillary electrophoresis of proteins.

PMID- 8564022
TI  - Applying genetic engineering to the structural analysis of proteins.
AB  - Genetic engineering offers many techniques that can be applied to the structural
      analysis of proteins. These techniques aid in the characterization of the protein
      but also can be applied to the generation of completely new diagnostic and
      therapeutic agents.

PMID- 8564023
TI  - Structural information on proteins from circular dichroism spectroscopy
      possibilities and limitations.

PMID- 8564024
TI  - Synaptic mechanisms of olfactory recognition memory.
AB  - The complexity and inaccessibility of the mammalian brain prevent the
      localization and description of memory traces and the definition of the processes
      that produce memories. The model reviewed here is the olfactory recognition
      memory formed to male pheromones by a female mouse at mating. The memory trace
      has been localized to the reciprocal dendrodendritic synapse between mitral cells
      and granule cells in the accessory olfactory bulb. An increase in noradrenaline
      after mating reduces inhibitory transmission of gamma-aminobutyric acid (GABA)
      from the granule cells to mitral cells and induces an olfactory memory of
      pheromones present at mating. Recent work has shown that the activation of
      mGluR2, a metabotropic glutamate receptor, localized at granule cell dendrites
      suppresses the GABA inhibition of the mitral cells and permits the formation of a
      specific olfactory memory that faithfully reflects the memory formed at mating.
      This simple olfactory memory may provide an excellent model system with which to
      investigate the molecular mechanisms of the synaptic plasticity involved in
      learning and memory.

PMID- 8564025
TI  - Gustatory function in the parabrachial nuclei: implications from lesion studies
      in rats.
AB  - In rodents, third order gustatory neurons reside in the parabrachial nuclei of
      the dorsal pons. Lesions in this area of the brain have a variety of consequences
      on taste-related behaviors. Some behaviors are severely impaired, such as the
      expression of either conditioned taste aversion or depletion-induced sodium
      appetite. Other taste-based behaviors are less affected or not influenced at all.
      Although the lesion-behavior approach possesses serious methodological
      limitations, the constellation of findings from studies employing this
      experimental strategy in the PBN has promising implications. Foremost among these
      is the suggestion that the neural circuitry subserving performance in some of
      these taste-guided behavioral paradigms is dissociable. This paper critically
      reviews this body of behavioral research and discusses the conceptual
      ramifications of the results.

PMID- 8564026
TI  - Transgenic mice and modeling Alzheimer's disease.
AB  - The etiology of Alzheimer's disease (AD) is poorly understood, and no effective
      therapies are available. Although histopathology of the disease has been studied
      thoroughly, the relationship of various AD lesions to pathological processes and
      to dementia are debated. Progress would be greatly enhanced by existence of
      manipulable small animal models of the disease. Recently, transgenic strategies
      to developing such a model have been extensively explored. The approach has
      proved to be difficult and has yielded some disappointments, but also some
      encouraging results. Transgenic strategies for obtaining a model for AD are
      surveyed in this review and, as an illustration, early AD-like features of
      transgenic mice produced in our laboratory are described.

PMID- 8564027
TI  - The morphologic and neurochemical basis of dementia: aging, hierarchical patterns
      of lesion distribution and vulnerable neuronal phenotype.
AB  - Alzheimer's disease is the most common form of dementia in elderly individuals.
      Approximately 11% of the population older than 65, and up to 50% of individuals
      over 85 qualify as having "probable Alzheimer's disease" on the basis of clinical
      evaluation. Since the early description of the clinical symptoms and
      neuropathologic features of Alzheimer's disease, there has been an extraordinary
      growth in the knowledge of the morphologic and molecular characteristics of
      Alzheimer's disease. Although the pathogenetic events that lead to dementia are
      not yet fully understood, several hypotheses regarding the formation of the
      hallmark pathologic structures of Alzheimer's disease have been proposed. In this
      context, the use of specific histochemical techniques in the primate brain has
      greatly expanded our understanding of neuron typology, connectivity and circuit
      distribution in relation to neurochemical identity. In this respect, very
      specific subsets of cortical neurons and cortical afferents can be identified by
      their particular content of certain neurotransmitters and structural proteins. In
      this article, we discuss the possible relationships between the distribution of
      pathologic changes in aging, Alzheimer's disease, and possibly related dementing
      conditions, in the context of the specific elements of the cortical circuitry
      that are affected by these alterations. Also, evidence for links between the
      neurochemical phenotype of a given neuron and its relative vulnerability or
      resistance to the degenerative process are presented in order to correlate the
      distribution of cellular pathologic changes, neurochemical characteristics
      related to vulnerability, and affected cortical circuits.

PMID- 8564028
TI  - Leg revascularization in the absence of the greater saphenous vein: alternatives
      and strategies. Introduction.

PMID- 8564029
TI  - Preoperative assessment of alternative veins.
AB  - Duplex ultrasonography, with or without color flow, has replaced phlebography as
      the technique of choice to select veins for autogenous bypass grafts. Although
      anatomic location and length are well-defined by ultrasound, evaluation of the
      venous wall itself is still imperfect. In situ diameters are less than those of
      arterialized veins. Ultrasonic search is most valuable in the examination of
      patients with good veins obscured by a layer of fat. Preoperative knowledge of
      variant anatomy and location of major veins and their branches facilitates bypass
      surgery. The preoperative vein mapping should be available in the operating room
      to guide the placement of incisions for unroofing and exploration directly over
      veins and vein segments that have a high likelihood of being usable. The finding
      of a useful vein when none is apparent on physical examination may enable the
      construction of an autogenous bypass in lieu of a less desirable prosthetic graft
      or leg amputation.

PMID- 8564030
TI  - Techniques and strategies using arm veins.

PMID- 8564031
TI  - Angioscopy of arm veins.

PMID- 8564032
TI  - The lesser saphenous vein.

PMID- 8564033
TI  - Composite autogenous vein grafts.

PMID- 8564034
TI  - Superficial femoral vein.

PMID- 8564035
TI  - Endarterectomy of the superficial femoral artery.

PMID- 8564036
TI  - Where the profunda femoris artery fits in the spectrum of lower limb
      revascularization.

PMID- 8564037
TI  - Prosthetic grafts: when are they a reasonable alternative?

PMID- 8564038
TI  - Improving the patency of prosthetic grafts with vein cuffs.

PMID- 8564039
TI  - Femoropopliteal and crural artery recanalization using subintimal angioplasty.

PMID- 8564040
TI  - What's new in gastrointestinal and hepatobiliary surgery.

PMID- 8564041
TI  - What's new in gynecology and obstetrics.

PMID- 8564042
TI  - What's new in neurological surgery.

PMID- 8564043
TI  - What's new in surgical oncology.

PMID- 8564044
TI  - What's new in ophthalmic surgery.

PMID- 8564045
TI  - What's new in orthopedic surgery.

PMID- 8564046
TI  - What's new in otorhinolaryngology.

PMID- 8564047
TI  - What's new in pediatric surgery.

PMID- 8564048
TI  - What's new in plastic surgery.

PMID- 8564049
TI  - What's new in general thoracic surgery.

PMID- 8564050
TI  - What's new in transplantation.

PMID- 8564051
TI  - What's new in trauma and burns.

PMID- 8564052
TI  - What's new in urology.

PMID- 8564053
TI  - What's new in vascular surgery.

PMID- 8564054
TI  - What's new in cardiac surgery.

PMID- 8564055
TI  - What's new in colon and rectal surgery.

PMID- 8564056
TI  - What's new in critical care and metabolism.

PMID- 8564057
TI  - Human fetal cardiocytes in enriched culture.

PMID- 8564058
TI  - Cell culture contamination by mycobacteria.

PMID- 8564059
TI  - Tight junctions and mucin mRNA in BEAS-2B cells.

PMID- 8564060
TI  - Tissue culture of dwarf embryonic pituitary glands.

PMID- 8564061
TI  - Rapid isolation of human endometrial stromal cells with high yield and purity.

PMID- 8564062
TI  - Culture of C2C12 and BC3H1 myogenic cells with iron-supplemented calf serum;
      rapid media screen.

PMID- 8564063
TI  - Milk-derived growth factors as serum supplements for the growth of fibroblast and
      epithelial cells.
AB  - We have investigated the response of several epithelial and fibroblastic cells to
      a mitogenic extract of bovine milk. Cation exchange chromatography was used to
      produce a mitogen-rich fraction from an industrial whey source that, although
      comprising only 0.5% of total whey protein, contained the bulk of the growth
      factor activity. This fraction was a source of potent growth promoting activity
      for all mesodermal-derived cells tested, including human skin and embryonic lung
      fibroblasts, Balb/c 3T3 fibroblasts, and rat L6 myoblasts. Maximal growth of all
      these cell types exceeded that observed in 10% fetal bovine serum. Feline kidney
      and baby hamster fibroblasts and Chinese hamster ovary cells were less
      responsive, achieving a maximal growth response of 50-75% that observed in 10%
      fetal bovine serum. Maximal growth achieved in whey-extract-supplemented cultures
      of Balb/c 3T3 and human skin fibroblasts, and L6 myoblast cultures exceeded that
      seen in response to recombinant acidic or basic fibroblast growth factor,
      platelet-derived growth factor, insulin-like growth factor, or epidermal growth
      factor. Importantly, addition of low concentrations of fetal bovine serum to the
      whey-derived mitogenic fraction produced an additive response. However,
      concentrated milk-derived factors were found to be inhibitory to the growth of
      all epithelial lines tested, including rat intestinal epithelial cells, canine
      kidney epithelial cells, and mink lung cells. It is concluded that industrial
      whey extracted in this form constitutes an important source of potent growth
      promoting agents for the supplementation of mesodermal-derived cell cultures.

PMID- 8564064
TI  - Epidermal cell proliferation and terminal differentiation in skin organ culture
      after topical exposure to sodium dodecyl sulphate.
AB  - Epidermal cell proliferation and differentiation were investigated in vitro after
      exposure to the anionic surfactant sodium dodecyl sulfate (SDS). Human skin organ
      cultures were exposed topically to various concentrations of SDS for 22 h, after
      which the irritant was removed. Cell proliferation was measured
      immunohistochemically by incorporation of bromodeoxyuridine (BrdU) into the DNA
      of cells during S-phase, while the expression of transglutaminase and involucrin
      were used as markers of differentiation. Cell proliferation was moderately
      increased at concentrations of SDS that did not affect the histomorphology (0.1%
      and 0.2% SDS). A marked increase of cell proliferation was observed 22 to 44 h
      after removal of SDS at a concentration (0.4%) that induced slight cellular
      damage. Exposure of human skin organ cultures to a toxic concentration of SDS
      91.0% led to decreased cell proliferation. Transglutaminase and involucrin were
      expressed in the more basal layers of the epidermis after exposure to 0.4% or
      1.0% SDS. Moreover, intra-epidermal sweat gland ducts were positive for
      transglutaminase at these irritant concentrations. These in vitro data
      demonstrate that SDS-induced alterations of epidermal cell kinetics, as described
      in vivo are at least partly due to local mechanisms and do not require the influx
      of infiltrate cells. However, we were unable to relate to altered cell kinetics
      to the release of interleukin-1 alpha or interleukin-6. Furthermore,
      supplementation of the culture medium with 12-hydroxyeicosantetraenoic acid did
      not affect epidermal cell proliferation. Rabbit skin cultures appeared more
      sensitive to SDS than human skin. At nontoxic doses, the irritant induced an
      increase of epidermal cell proliferation, similar to that observed in human skin
      discs.

PMID- 8564066
TI  - Culturing satellite cells from living single muscle fiber explants.
AB  - Conventional methods for isolating myogenic (satellite) cells are inadequate when
      only small quantities of muscle, the tissue in which satellite cells reside, are
      available. We have developed a tissue culture system that reliably permits
      isolation of intact, living, single muscle fibers with associated satellite cells
      from predominantly fast and slow muscles of rat and mouse; maintenance of the
      isolated fibers in vitro; dissociation, proliferation, and differentiation of
      satellite cells from each fiber; and removal of the fiber from culture for
      analysis.

PMID- 8564065
TI  - Characterization of human and rat immortalized clones parotid acinar cells with
      respect to specific proteins and their mRNAs, and receptor-linked adenylate
      cyclase.
AB  - This study reports the isolation and characterization of a rat nontumorigenic
      parotid acinar cell clone (2RSG), a human nontumorigenic parotid acinar cell
      clone (2HPC8), and a human tumorigenic acinar clone (2HP1G). The levels of alpha
      amylase mRNAs detected when using alpha-amylase cDNA of 1176 and 702 bp for
      hybridization were higher in 2RSG and 2HPC8 cells than their respective whole
      parotid glands. The level of these mRNAs decreased in 2HP1G cells. In contrast to
      alpha-amylase mRNAs levels, the alpha-amylase activity in cultured acinar cells
      was extremely low in comparison to whole glands, irrespective of species or cell
      status. The levels of proline-rich protein (PRP) mRNA and parotid secretory
      protein (PSP) mRNA detected when using PRP cDNA of 600 bp and PSP cDNA of 805 bp
      for hybridization were higher in 2RSG cells than those in rat parotid glands; the
      reverse was observed in 2HPC8 cells and human parotid glands. The levels of PRP
      mRNA and PSP mRNA in 2HPC8 and 2PH1G acinar cells were similar. The level of mRNA
      was not detectable in murine neuroblastoma cells (NBP2) using the same alpha
      amylase cDNA, PRP cDNA and PSP cDNA for hybridization. The PSP level in rat
      parotid gland was lower than that found in 2RSG cells; the reverse was observed
      in 2HPC8 cells and human parotid glands. The level of PSP in 2HP1G cells was
      higher than that found in 2HPC8 cells. Isoproterenol increased the cAMP level in
      2RSG, 2HPC8, and 2HP1G clones, being most effective in 2RSG cells, and least
      effective in 2HPG cells. Prostaglandin E1 (PGE1) also increased cAMP level, being
      most effective in 2HPC8 cells and ineffective in 2HP1G cells, suggesting that the
      PGE1 receptor-linked adenylate cyclase becomes inactive upon transformation.
      These results suggest that the three clonal acinar cells from rat and human
      parotid glands reported here can be useful in comparative studies on regulation
      of growth, differentiation, and transformation.

PMID- 8564067
TI  - Isolation and characterization of biliary epithelial cells from rainbow trout
      liver.
AB  - Lectin binding and density gradient centrifugation were explored for isolating
      epithelial cells from trout liver. Hepatocytes exhibited preferential attachment
      of coverslips coated with Phaseolus vulgaris erythroagglutinin. Biliary
      epithelial cells attached with glycine max agglutinin; however, significant
      attachment of cellular debris limited the use of glycine max agglutinin. Percoll
      density gradient centrifugation separated liver cells into two distinct
      populations with biliary cells and hepatocytes banding at densities of 1.04 and
      1.09, respectively. A discontinuous gradient composed of 13% Ficoll (wt/wt)
      separated biliary cells from hepatocytes. The recovery of highly enriched biliary
      epithelial cells from trout liver using Ficoll gradients yielded approximately 8
      million cells (0.1 ml packed cells) from 10 g liver. Western blot analysis
      demonstrated that the cytokeratin profile for extracts from biliary epithelial
      cell-enriched populations differ significantly from those seen with whole liver
      extracts or with extracts with hepatocyte-enriched populations. Ficoll-gradient
      purified biliary cells and hepatocytes attached to culture plates coated with
      trout skin extract and carried out linear incorporation of leucine into protein
      and thymidine into DNA for 24 h. A mixture of growth hormones (insulin, epidermal
      growth factor, and dexamethasone) stimulated thymidine incorporation into DNA;
      however, long-term culture of dividing biliary epithelial cells was not achieved.
      Chemical analysis of neutral and acidic glycolipids indicated that hepatocytes
      and biliary cells have similar glycolipid profiles with an exception in the
      region of GM3 mobility, which is attributed to differences in the ceramide
      moiety. These studies provide a starting point for further characterization of
      unique cell types of the trout liver that may be important in their responses to
      toxic and carcinogenic agents.

PMID- 8564068
TI  - Role of protein kinase C in growth stimulation of primary mouse colonic
      epithelial cells.
AB  - The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (160 nM) and the
      secondary bile acid, deoxycholic acid (50 microM) stimulated DNA synthesis in
      quiescent primary epithelial cells from the normal mouse colon as measured by
      autoradiographic analysis of [3H]thymidine incorporation. The purpose of this
      present study was to investigate the involvement of protein kinase C in the
      proliferative response of the normal colonic cells. The protein kinase C
      inhibitor, bisindolyl-maleimide GF 109203X, efficiently blocked the proliferative
      response of the cells to the phorbol ester and caused a dose-dependent decrease
      in the response to deoxycholic acid. While the phorbol ester-induced
      proliferation was unaffected by another inhibitor, H-7, the response of the cells
      to deoxycholic acid was blocked. Pretreatment of the cells with the phorbol ester
      (160 nM) for 24 h blocked the proliferative response to deoxycholic acid.
      Measurement of the intracellular distribution of protein kinase C activity showed
      a time-dependent and significant translocation of the enzyme activity from the
      soluble to the particulate cell fractions after exposure to 12-O
      tetradecanoylphorbol-13-acetate. While exposure to the bile acid indicated a
      similar time-dependent translocation of the enzyme activity, the effect was not
      significant. The phorbol ester induced a time-dependent accumulation of c-fos
      mRNA and protein was measured by solution hybridization and immunocytochemistry,
      respectively. No effect of deoxycholic acid on c-fos expression could be observed
      in the present study. The data support a role for protein kinase C in the growth
      stimulating effect of physiological concentrations of deoxycholic acid on normal
      colonic epithelial cells. However, differences in the mechanisms underlying
      phorbol ester- and bile acid-induced proliferation are indicated.

PMID- 8564069
TI  - Actin cytoskeletal isoforms in human endothelial cells in vitro: alteration with
      cell passage.
AB  - The microfilamentous actin component of the cytoskeleton is crucial to
      endothelial angiogenesis and vascular permeability. Differences in actin
      cytoskeletal profiles in cultured human endothelial cells were explored: when
      first isolated, both primary human umbilical vein endothelial cells (HUVEC) and
      primary human placental microvascular endothelial cells (HPMEC) expressed F
      actin, but not beta-actin or alpha-smooth muscle actin. A similar endothelial
      actin profile was observed in cryo-sections of freshly delivered term umbilical
      cord and placenta. In subsequent cell culture, although the actin cytoskeleton of
      HUVEC remained unchanged, the actin profiles of HPMEC altered after the second
      passage with the induction of alpha-smooth muscle actin expression, which was
      intercellularly heterogeneous and increased to 20% at P4. This behaviour occurred
      in HPMEC monolayers cultured on a variety of extracellular matrices. Comparisons
      with a spontaneously immortalized human microvascular cell-line, HGTEN 21,
      revealed that in prolonged passage, both alpha-smooth muscle actin and beta-actin
      were expressed, whereas HPMEC at P4 showed a lower level of beta-actin
      expression. Therefore, in comparison with large vessels, microvascular cells are
      more likely to dedifferentiate. This may reflect the ability of microvascular
      cells to remodel according to changing requirements for new vessel formation. In
      conclusion, passage of human microvascular endothelial cells, but not of larger
      vessel endothelial cells, alters the expression of actin isoforms. This may be
      important in relation to comparisons of in vitro and in vivo vascular
      permeability; higher passage microvascular endothelial cells should thus be used
      with caution in such studies.

PMID- 8564070
TI  - Effect of juvenile hormone on the embryogenesis of a polyembryonic wasp,
      Copidosoma floridanum, in vitro.
AB  - Single two-cell-stage embryos of a polyembryonic wasp Copidosoma floridanum
      cultured in 20 microliters droplets of culture medium developed to morulae at the
      same developmental rate as those in host eggs, but the subsequent development
      into polymorulae was inferior. This inferior development was markedly improved by
      addition of juvenile hormone (I, II, or III) or its analogues to the culture
      medium in a concentration-dependent manner.

PMID- 8564071
TI  - Increase in total protein following infection of CV-1 cells with SV40 virus as
      assayed by flow cytometry.
AB  - The changes in cell size and total protein were determined for G1-arrested,
      contact-inhibited CV-1 cells infected with Simian virus 40 (SV40). The assays
      used were the Biorad total protein assays (Bradford and DC protein assays) on a
      standard number of cells, total protein as assayed by fluorescein isothiocyanate
      (FITC) and SR101 by flow cytometry, orthoganol (90 degrees) light scatter by flow
      cytometry, and direct microscopic measurement with an ocular micrometer.
      Uninfected CV-1 cells and two cell lines with variations in DNA content (diploid
      vs. tetraploid) were used as controls for the studies presented. The results
      demonstrated a 40-60% increase in total protein at 32 to 42 h postinfection.
      These increases were similar to values obtained due to cellular changes resulting
      from viral replication and cell death.

PMID- 8564073
TI  - Implication of TGF beta 1 in co-culture of chondrocytes-osteoblasts.

PMID- 8564072
TI  - Upregulation of heparin-affin regulatory peptide by androgen.

PMID- 8564074
TI  - Culture of Hermissenda crassicornis (Mollusca) neurons.

PMID- 8564075
TI  - Hypotonic lysis of red blood cell contamination from human anterior pituitary
      adenoma cell preparations.

PMID- 8564076
TI  - Intrinsic glycosylation potentials of insect cell cultures and insect larvae.
AB  - The glycosylation and subsequent processing of native and recombinant
      glycoproteins expressed in established insect cell lines and insect larvae were
      compared. The Spodoptera frugiperda (Sf21) and Trichoplusia ni (TN-368 and BTI-Tn
      5B1-4) cell lines possessed several intrinsic glycoproteins that are modified
      with both N- and O-linked oligosaccharides. The N-linked oligosaccharides were
      identified as both the simple (high mannose) and complex (containing sialic acid)
      types. Similarly, the T. ni larvae also possessed intrinsic glycoproteins that
      were modified with O-linked and simple and complex N-linked oligosaccharides.
      Additionally, human placental, secreted alkaline phosphatase (SEAP) produced
      during replication of a recombinant baculovirus in T. ni larvae was modified with
      complex oligosaccharide having sialic acid linked alpha(2-6) to galactose.

PMID- 8564077
TI  - Characterization of bovine oviduct epithelial cell monolayers cultured under
      serum-free conditions.
AB  - We have developed a culture system for early bovine embryos in serum-free media
      conditioned by oviduct cell monolayers. A gentle mechanical procedure for oviduct
      cell isolation has been applied for this purpose avoiding the use of proteolytic
      enzymes. The aim of the present study was to identify the cell types present in
      the monolayers and to examine their fate in primary culture in serum-free or in
      serum-containing media by means of electronmicroscopical, immunocytochemical, and
      biochemical analyses. The cell dissociation procedure yielded two cell
      populations: ciliary cells and secretory cells that gradually dedifferentiate
      during culture. These cells formed a confluent monolayer after 6 d of culture in
      Tissue Culture Medium 199 medium supplemented with 10% fetal calf serum.
      Confluent cells displayed a typical epithelial cell morphology as assessed by
      phase contrast and electron microscopy and all the cells contained cytokeratin
      filaments as determined by immunocytochemistry. The overall histoarchitecture of
      the monolayer was preserved after washing and further culture for 7 d in serum
      free medium. However, some degenerative signs indicate that the serum-free
      culture should not be extended for more than 7 d. Confluent oviduct cells also
      maintained their metabolic and protein secretory activity when deprived of serum.
      Total protein content in the culture supernatant linearly increased as a function
      of time and numerous peaks were detected after separation of proteins by high
      performance ion exchange chromatography. Protein elution patterns were
      reproducible and most of the proteins present in the culture medium were
      neosynthesized as determined by the incorporation of radiolabeled amino acids
      into nondialyzable proteins.

PMID- 8564078
TI  - Heparin and the phenotype of adult human vascular smooth muscle cells.
AB  - To study mechanisms controlling growth and phenotype in human vascular smooth
      muscle cells, we established culture conditions under which these cells
      proliferate rapidly and achieve life-spans of 50-60 population doublings. In
      medium containing heparin and heparin-binding growth factors, growth rate and
      life-span of human vascular smooth muscle cells increased more than 50% relative
      to cultures with neither supplement, and more than 20% compared to cultures
      supplemented only with heparin-binding growth factors. In contrast to
      observations made in rat vascular smooth muscle cells, smooth muscle-specific
      alpha-actin in the human cells was expressed only in the presence of heparin and
      colocalized with beta/gamma nonmuscle actins in stress fibers, not in adhesion
      plaques. Heparin, in the presence of heparin-binding growth factors, also caused
      more than 170% stimulation of tracer glucosamine incorporation into hyaluronic
      acid and a 7.5-fold increase in hyaluronic acid accumulation. In comparison,
      total sulfate incorporation into sulfated glycosaminoglycans increased by less
      than 40%. In light of our previous findings that heparin suppresses collagen gene
      expression, we conclude that heparin induces human vascular smooth muscle cells
      exposed to heparin-binding growth factors to remodel their extracellular matrix
      by altering the relative rates of hyaluronic acid (HA) and collagen synthesis.
      The resulting hyaluronic-acid-rich, collagen-poor matrix may enhance infiltration
      of CD44/hyaluronate-receptor-bearing T-lymphocytes and monocytes into the
      vascular wall, an early event in atherogenesis.

PMID- 8564079
TI  - Isolation and characterization of rat primary lung cells.
AB  - Lung cell culture may be useful as an in vitro alternative to study the
      susceptibility of the lung to various toxic agents. Lungs from female Wistar rats
      were enzymatically digested by recirculating perfusion through the pulmonary
      artery with a sequence of solutions containing deoxyribonuclease, chymopapain,
      pronase, collagenase, and elastase. Lung tissue was microdissected and
      resuspended and the cells obtained were washed by centrifugation. By this
      isolation method, 2 x 10(8) cells per rat lung were obtained with an average
      viability of 97%. Lung cells cultured in medium containing antibiotics and serum
      maintained a viability of > 70% for 5 d. Rat primary lung cells were exposed to
      various toxic agents and their viability was assessed by formazan production
      capacity after 18 h of incubation. Compared to rat and mouse hepatocyte cultures
      (EC50 = 5.8 mM), rat primary lung cells were much more susceptible to hydrogen
      peroxide (EC50 = 0.6 mM). All cell types were equally sensitive to the more
      potent toxicant tert-butylhydroperoxide (EC50 = 0.1 mM). Paraquat was more toxic
      to lung cells (EC50 = 0.03 mM) than to rat (EC50 = 2.8 mM) and mouse (EC50 = 0.2
      mM) hepatocytes. In contrast, rat lung cells were less sensitive to sodium
      nitroprusside (EC50 = 2.6 mM) compared to rat (EC50 = 0.2 mM) and mouse (EC50 =
      0.03 mM) hepatocytes. Nitrofurantoin and menadione (at EC50 = 0.04 mM and 0.006
      mM, respectively) were more toxic to rat lung and liver cells than to murine
      hepatocytes (EC50 = 0.2 mM and 0.04 mM, respectively). Our findings demonstrate
      the applicability of this rat primary lung cell culture for studying the effects
      of lung toxicants.

PMID- 8564080
TI  - Use of a DNA microfluorometric assay to measure proliferative response of mink
      lung cells to purified TGF beta and to TGF beta activity found in prostate cell
      conditioned medium.
AB  - The proliferative response of Mv1Lu cells to purified TGF beta 1, or TGF beta
      like activity released by various cells into medium conditioned over a 24-h
      period was quantitated by adapting a rapid DNA fluorometric assay. Acid
      activation of the conditioned medium allowed the amount of biologically latent
      versus active TGF beta to be quantitated. A neutralizing antibody specific for
      TGF beta 1, 1.2, and 2.0 completely blocked the growth inhibition observed
      treating Mv1Lu cells with either purified TGF beta 1 or medium containing
      secreted TGF beta-like activity conditioned by DU145 prostate cells. In contrast
      to other assays commonly used to measure TGF beta activity, the proliferative
      response is related directly to DNA content rather than as a reflection of
      enzymatic activity or incorporation of 3H-thymidine. The necessity for
      radioactive isotope usage has been eliminated, and the biological response can be
      quantitated over a period of days.

PMID- 8564081
TI  - The effect of recombinant human basic fibroblast growth factor rhFGF-2 on human
      osteoblast in growth and phenotype expression.
AB  - This paper describes the studies of human recombinant basic fibroblast growth
      factor (rhFGF-2) for its effects on human osteoblast growth and phenotype
      expression. During a 24-h period of treatment, rhFGF-2 highly stimulated DNA
      synthesis in a dose-related fashion with a maximum stimulation of 150% for 1
      ng/ml. On the other hand, rhFGF-2 decreases alkaline phosphatase activity,
      synthesis of type I collagen, and cumulative amount of osteocalcin. Moreover,
      rhFGF-2 provoked a threefold increase in the amount of intracellular cAMP.
      Scatchard plots show the presence of two classes of [125I] rhFGF-2 receptors.
      This data suggests that rhFGF-2 which stimulate cell replication may act
      indirectly as an anabolic agent and stimulate some of the phenotypic expression
      markers.

PMID- 8564083
TI  - Application of PCR for detection and identification of mycoplasma contamination
      in virus stocks.
AB  - A nested polymerase chain reaction (PCR) was used to detect and identify
      mycoplasma contaminants in viral stocks. The results of the PCR assay proved to
      be a sensitive and accurate indicator of the true status of the stock tested.
      Those samples positive by agar culture or Hoechst stain were also positive by
      PCR. Those samples that were inconclusive by Hoechst stain (10.05%) could be
      clearly determined to be mycoplasma positive or negative by PCR. The PCR assay
      also detected those fastidious species of mycoplasma that gave false negative
      results by the direct culture method. In many respects the PCR-based mycoplasma
      detection method described is superior to the agar culture and Hoechst staining
      detection methods. In this study, the PCR assay detected substantially more
      mycoplasma-positive viral stocks than did the agar culture assay. Due to its
      speed, sensitivity, and reliability, the PCR assay is of particular value in
      monitoring the process of removing mycoplasma from contaminated stocks.
      Furthermore, the PCR amplification products can be analyzed by restriction
      analysis to rapidly identify the species of the mycoplasma contaminating the
      stock tested.

PMID- 8564082
TI  - DNA binding by C/EBP proteins correlates with hepatocyte proliferation.
AB  - The leucine zipper transcription factors C/EBP alpha and C/EBP beta exhibit
      growth-related variations of expression and DNA binding during liver
      regeneration. We examined the expression of C/EBP proteins in relation to
      hepatocyte proliferation by studying their DNA-binding activity in primary mouse
      hepatocytes in vitro. Mouse hepatocytes were dissociated by collagenase perfusion
      and cultured in a serum-free, defined medium containing a variety of growth
      factors and hormones. Cell protein extracts were collected every 24 h for up to
      10 d and examined for DNA-binding activity by gel retardation analysis using a
      C/EBP consensus sequence oligomer (bZIP). C/EBP alpha is the major bZIP-binding
      protein present in the dissociated cells prior to plating. With the culture
      conditions we employed, little or no binding of C/EBP proteins was observed in
      the first 24 to 48 h of cultivation. After 48 h, C/EBP beta binding activity was
      elevated relative to the level seen in freshly dissociated cells. In contrast,
      C/EBP alpha binding continued to be greatly reduced and no C/EBP delta binding
      was observed. C/EBP beta binding remained elevated for the duration of the
      experiment. Additional growth factor treatment (EGF, FGF, TGF alpha, and HGF) of
      the hepatocytes did not appreciably alter the pattern of C/EBP binding. However,
      TGF beta treatment, known to decrease hepatocyte proliferation, increased C/EBP
      beta binding activity earlier and more actively than in control cells. This study
      confirms a negative correlation between DNA binding by the C/EBP transactivator
      proteins and the proliferation of primary mouse hepatocytes in vitro.

PMID- 8564084
TI  - Use of a renal tubule cell line (LLC-PK1) to study the nephrotoxic potential of a
      kappa-type Bence-Jones protein.
AB  - The cytotoxicity of a Bence-Jones protein was assessed using a porcine renal
      tubule cell line (LLC-PK1), with the aim of developing a model for studying the
      potential nephrotoxicity of these proteins. The effects of a kappa Bence-Jones
      protein on cell viability were studied by means of biochemical methods
      (supravital dye uptake and measurement of cellular enzyme activities) and
      morphological electron microscopy. After a 24-h-treatment with Bence-Jones
      protein, a moderate cytotoxicity (about 15%) was noted but only a minor
      difference compared to treatment with bovine albumin in the same conditions. The
      morphological study showed a few cells in the process of lysis, but their numbers
      were insufficient for the demonstration of a clear cytotoxic effect.
      Immunocytochemical studies showed Bence-Jones protein fixation on some cells,
      especially on the outer membrane. Labeling of the hyaloplasm and basal pole of a
      few cells pointed to internalization of protein by LLC-PK1 cells. Although the
      cytotoxicity of the Bence-Jones protein tested here was only moderate, the use of
      this model enabled its cytotoxic effect to be distinguished from that of beta
      lactoglobulin. This isolate could serve as a "moderate control" for a later study
      with a BJP having caused acute renal failure.

PMID- 8564085
TI  - Molecular cloning of yeast cytochrome c-like polypeptide expressed in human lung
      carcinoma: an antigen recognizable by lung cancer-specific human monoclonal
      antibody.
AB  - We previously determined the amino acid sequence to the epitope (ATLFKTR) of
      cytochrome c from Candida krusei, which is cross-reactive to the lung cancer
      specific human monoclonal antibody HB4C5. Here we report that an antigen
      messenger RNA, which codes for a structure similar to the cytochrome c epitope,
      is expressed in the human lung adenocarcinoma A549. Sequencing analysis has
      revealed that this messenger RNA encodes a novel 190 amino acid polypeptide of 21
      kDa containing an amino acid sequence (ALLFFT) similar to the cytochrome c
      epitope, although the total messenger RNA sequence is apparently different from
      the cytochrome c messenger RNA. Western analysis indicated that an antibody
      recognizable 21-kDa antigen which has the same molecular weight as the predicted
      polypeptide is expressed in the A549 adenocarcinoma. The in vitro translated
      product of the antigen messenger RNA and synthesized ALLFFT peptide were both
      shown to be reactive with the monoclonal antibody, indicating that this protein
      contains the epitope which enables A549 cells to specifically react with the
      antibody. The antigen mRNA was not expressed in non-transformed fibroblasts,
      suggesting that the antigen mRNA expression was associated with cellular
      transformation. Also in part of the antigen nucleotide sequence, there was a
      segment that had about 90% homology to the long terminal repeat sequence (no. 297
      475) of the human endogenous retrovirus HERV-K10, which was related to the mouse
      mammary tumor virus.

PMID- 8564086
TI  - Health effects of outdoor air pollution. Part 2. Committee of the Environmental
      and Occupational Health Assembly of the American Thoracic Society.
AB  - Although sources of airborne lead have been reduced over the last decade,
      particularly with the use of lead-free gasoline, there are still relatively high
      levels of lead contamination in soils and the residential housing stock built
      before the 1970s, which pose a risk for continued direct exposure through
      ingestion or airborne exposure if resuspended. Neurobehavioral effects,
      particularly as a result of early childhood exposures, have been documented, and,
      because of the way lead is stored in the body, late effects can become manifest
      during periods of high bone turnover (e.g., pregnancy, lactation, or
      hyperthyroidism). Late consequences not only relate to lead excretion affecting
      the fetus or newborn but also appear to be associated with hypertension in
      adults. Control of exposure in early life is an important component of
      appropriate preventive action.

PMID- 8564087
TI  - The controversy over emergency research. A review of the issues and suggestions
      for a resolution.
AB  - Emergency research that occurs upon critically ill subjects in circumstances that
      do not allow the subjects or their legally authorized representatives to grant an
      informed consent is currently the subject of great controversy. This Clinical
      Commentary reviews three issues that dominate the debate: research risk
      assessment, the concept of a particular kind of risk called minimal risk, and the
      regulations governing research on human subjects. The theses of this article are
      that Institutional Review Boards (IRBs) are not violating Office of Protection
      from Research Risks (OPRR) regulations, that Food and Drug Administration (FDA)
      regulations do not adequately address research design, and that emergency
      research fits within the ethical standards of justice, respect for autonomy, and
      beneficence. To defend these claims, the following points are argued: risk
      assessment is a moral or transscientific exercise, minimal risk refers to the
      increment of risk that the subject of the research faces, and that when equipoise
      exists between experimental and standard therapies, this state of uncertainty
      contributes to a study's justifications. In order to resolve the emergency
      research controversy, certain regulations will need to be rewritten and others
      reinterpreted, and a national board created to review a proposed study's clinical
      relevance and whether the current state of knowledge justifies a trial.

PMID- 8564088
TI  - Ethical considerations of new guidelines for emergency research.

PMID- 8564089
TI  - Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid
      sparing agent in corticosteroid-dependent asthma.
AB  - Patients with severe asthma who require long-term oral corticosteroid therapy are
      at risk of unwanted effects. Several immunosuppressive drugs have been assessed
      as corticosteroid-sparing agents in chronic asthma. We previously showed that
      cyclosporin A (CsA) administered for 12 wk improved lung function in
      corticosteroid-dependent patients. We have now investigated the corticosteroid
      sparing properties of CsA over a 36-wk period. Following a 4-wk run-in period, 39
      corticosteroid-dependent asthmatic patients were randomized to receive CsA (19
      patients, initial doses 5 mg/kg/d) or matched placebo (20 patients) for 36 wk.
      Attempts were then made by a physician ignorant of the trial therapy to reduce
      their prednisolone dosages at 14-d intervals, provided that a patient's asthma
      remained stable or improved. Three patients receiving CsA had to be withdrawn
      from the study before they completed 12 wk of therapy. The remaining 16 patients
      achieved a statistically significant reduction in median daily prednisolone
      dosage of 62% (10 to 3.5 mg), compared with a decrease of 25% (10 to 7.5 mg) in
      the patients taking placebo (p = 0.043). This reduction was most pronounced
      during the last 12 wk of active therapy. In addition, morning peak expiratory
      flow rate (PEFR) improved significantly (mean 9.4%, SEM 3.0%) in the active
      treatment group but not in the placebo group (p = 0.026 between groups).
      Predictable changes in renal function and blood pressure, and an increased
      incidence of hypertrichosis and paresthesia, were observed in the patients
      treated with CsA, but these did not necessitate withdrawal from the study, and
      were reversed during a 4-wk run-out period. Thus, low-dose CsA therapy, as
      compared with placebo, allowed a significant reduction in oral corticosteroid
      dosages in patients with severe asthma, and also improved lung function.

PMID- 8564090
TI  - Inflammatory and T-cell profile of asthmatic airways 6 hours after local allergen
      provocation.
AB  - T cells in the airways are considered to play a key role in orchestrating the
      inflammatory response of asthma through the elaboration of specific cytokines.
      Using flow cytometry we have investigated the T-cell response of sensitized
      asthmatic airways 6 h after local allergen provocation. Twelve subjects with
      atopic asthma underwent bronchoalveolar lavage (BAL) before and 6 h after local
      instillation of allergen into the right middle lobe (RML) and saline into the
      right upper lobe (RUL). Allergen challenge produced a significant 26% fall in
      FEV1, an increase in eosinophils in BAL at 6 h, and at 24 h an increase in
      methacholine responsiveness compatible with late-phase airway inflammation. When
      compared with saline challenge, allergen produced an overall decrease in the
      number of BAL lymphocytes from 21.3 +/- 2.8% to 16.0 +/- 3.08% of total cells but
      no change in the proportion of CD4+, CD8+, CD25+, or HLA-DR+ cells. Allergen
      provocation reduced the proportion of T cells expressing the beta 2 integrin
      lymphocyte functional antigen-1 (LFA-1) from 72.5 +/- 30 to 43.9 +/- 9.1 mean
      fluorescent units (p < 0.01) and a similar trend in intercellular adhesion
      molecule-1 (ICAM-1) (p = 0.08). These results indicate that late-phase
      inflammatory events 6 h after local allergen provocation involve the selective
      retention of airway T cells expressing specific cell adhesion molecules.

PMID- 8564091
TI  - LFA-1, and not Mac-1, is crucial for the development of hyperreactivity in a
      murine model of nonallergic asthma.
AB  - In this study, we investigated the importance of the beta 2-integrins for the
      development of tracheal hyperreactivity in a murine model for nonallergic asthma.
      The response was induced by skin sensitization with dinitrofluorobenzene (DNFB)
      followed by an intranasal challenge with the same hapten. Twenty-four hours after
      the challenge, tracheal hyperreactivity, a decrease in T cells in the blood, and
      increased neutrophil numbers in bronchoalveolar lavage fluid (BALF) and blood
      were observed. Monoclonal antibodies (mAbs) directed against the alpha-chains of
      LFA-1 (FD441.8) and Mac-1 (M1/70) were injected intravenously 2 h before and 2 h
      after the challenge. Treatment with anti-LFA-1 mAb totally inhibited the
      development of tracheal hyperreactivity measured 24 h after the challenge,
      whereas anti-Mac-1 mAb had only a partial effect on this response. The decrease
      in T cells in the blood, which was also evident 24 h after the challenge, was
      totally inhibited by treatment with anti-LFA-1, whereas anti-Mac-1 had little
      effect. The increase in the number of neutrophils in BALF at this time point was
      completely inhibited by both anti-LFA-1 and anti-Mac-1. In summary, evidence
      presented in this report highlights the possible importance of the adhesion
      molecule LFA-1 in the development of tracheal hyperreactivity. Our results
      suggest that LFA-1 present on T cells may play an integral role in this response.

PMID- 8564092
TI  - Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum
      from patients with chronic obstructive pulmonary disease or asthma.
AB  - Asthma and chronic obstructive pulmonary disease are characterized by chronic
      airway inflammation. Studies using bronchoalveolar lavage (BAL) have shown an
      increased proportion of eosinophils in the BAL fluid from asthmatics compared
      with that from normal subjects, whereas studies of chronic obstructive pulmonary
      disease (COPD) have shown increased numbers of neutrophils. Induced sputum allows
      sampling of respiratory tract secretions from patients and control subjects,
      providing a noninvasive method of studying airway secretions and allowing
      characterization of cells and measurement of soluble markers. We investigated
      whether induced sputum was a useful method of studying airway fluid from patients
      with moderate to severe COPD and whether it could be used to compare inflammation
      in this condition with that in asthma. An initial reproducibility study was
      undertaken. Sputum was induced twice in 13 patients with severe COPD at a 14-d
      interval. Total and differential cell counts were carried out and were found to
      be reproducible over this period. Sputum was then induced in 14 patients with
      COPD, 23 patients with asthma, 12 healthy cigarette smokers, and 16 normal
      nonsmoking control subjects. We found a significant increase in neutrophils and
      increased concentrations of tumor necrosis factor-alpha (TNF alpha) and
      interleukin-8 (IL-8) in the patients with COPD compared with the smoking and
      nonsmoking control subjects. Interleukin-8, but not TNF alpha, was significantly
      higher in the COPD group than in the asthmatic group. We conclude that the
      cytokines TNF alpha and IL-8 may be involved in the inflammation in COPD.

PMID- 8564093
TI  - Interleukin-12 inhibits antigen-induced airway hyperresponsiveness in mice.
AB  - The airway inflammation observed in allergic asthma is thought to be orchestrated
      by an antigen-driven T-helper-2 (Th2) lymphocyte response. In vitro data indicate
      that the presence of interleukin-12 (IL-12) during the primary stimulation of T
      lymphocytes with antigen favors the development of Th1 cells. The aim of the
      present study was to examine the effect of IL-12 in vivo on antigen-induced
      airway changes in a murine model. C57BL/6 mice were actively sensitized to
      ovalbumin; 14 d later, they were exposed daily for 7 d to aerosolized ovalbumin.
      This resulted in airway eosinophilia, production of ovalbumin-specific IgE, and
      airway hyperresponsiveness to carbachol. Administration of recombinant murine IL
      12 (rmIL-12) during the active immunization prevented these antigen-induced
      changes. In contrast, administration of rmIL-12 to actively immunized mice during
      the daily aerosol exposure (but not at the time of immunization) abolished airway
      eosinophilia and hyperresponsiveness without influencing the production of
      specific IgE. These results suggest that IL-12 can suppress antigen-induced
      airway changes despite the presence of circulating specific IgE.

PMID- 8564094
TI  - Elevated B cells in sputum of asthmatics. Close correlation with eosinophils.
AB  - Sputum examination is a useful noninvasive method to study airway inflammation.
      We investigated the reproducibility and validity of the measurements of
      lymphocyte subsets in the sputum of 11 stable patients with asthma and 10
      nonasthmatic smokers. Sputum was dispersed with 0.1% dithiothreitol. A
      differential cell count was made with Wright's stain. Aliquots were stained with
      antibodies to CD19 (B cells), CD3 (T cells), CD4 (helper), CD8 (suppressor), and
      the activation marker CD25 (IL2 receptor) on T-cell subsets and were assayed by
      flow cytometry. Sputum from patients with asthma compared with nonasthmatic
      subjects had more eosinophils (mean +/- SEM, 32.5 +/- 8.5 versus 1.3 +/- 0.5%, p
      < 0.01) and a higher proportion of lymphocytes that were B cells (16.2 +/- 3.2
      versus 4.0 +/- 1.0%, p < 0.01), and these correlated closely with the eosinophils
      (r = 0.8, p < 0.01). Patients with asthma also had more activated T-helper cells
      (39.3 +/- 4.6 versus 9.0 +/- 9.0%, p = 0.05), but the comparison was limited to
      two smokers because of macrophage autofluorescence. The repeatability of
      measurements of helper T-cells (R = 0.94), suppressor T cells (R = 0.88), and
      activated helper T cells (R = 0.77) was good; repeatability of measurements of T
      and B cells could not be examined because these were reciprocals of each other.
      Asthmatic sputum has different lymphocyte profiles than sputum from nonasthmatic
      smoking control subjects. The results demonstrate a potential importance of
      antibody-producing lymphocytes in the airway and their relation to sputum
      eosinophilia in asthma.

PMID- 8564095
TI  - The role of endogenous corticosterone in the late-phase response to allergen
      challenge in the brown Norway rat.
AB  - The aim of this study was to assess the role of endogenous corticosterone (CCST)
      concentrations on the late airway response (LAR) to ovalbumin (OA). Thirty-two
      Brown Norway (BN) rats were sensitized to OA on Day 0, then divided into three
      groups. Group 1 (n = 11) received saline (1 ml, subcutaneously) at time (T) = 
      24, -12, and 0 h prior to a 5% OA challenge on Day 14. Group 2 (n = 11) received
      metyrapone (MTP), an 11 beta-hydroxylase inhibitor, (10 mg/100 g in 1 ml saline,
      subcutaneously) at time (T) = -24, -12, and 0 h. Group 3 (n = 10) received MTP on
      the same schedule as Group 2, plus CCST in the drinking water (16 micrograms/ml)
      from T = -24 to T = 0 h. Pulmonary resistance (RL) was measured for 8 h following
      OA challenge to determine early (EAR) and LAR. Blood samples were taken at T = 0
      and T = 8 h to determine serum CCST levels. Bronchoalveolar lavage (BAL) fluid
      was collected at T = 8 h. Serum CCST levels were significantly reduced in the MTP
      group (235 ng/ml +/- 14 SEM) compared with control (564 +/- 38, p < 0.0001) and
      MTP+CCST animals (349 +/- 19, p < 0.0005). There were no differences in either
      baseline RL or EAR between the groups. However, the MTP group had a smaller LAR
      (6 ml/cm H2O/s*min +/- 2 SEM) than the control group (19 +/- 5, p < 0.02). The
      effect of MTP on LAR was reversed by treatment with CCST (21 +/- 3, p < 0.005).
      Total cell counts (p < 0.05) and eosinophils (p < 0.01) were increased in the BAL
      fluid of MTP rats versus control and MTP+CCST animals. We conclude that depletion
      of endogenous CCST in the BN rat diminishes the LAR to allergen challenge. These
      results indicate that physiologic levels of CCST are not necessary for
      development of the EAR, but they play a permissive role in the LAR to inhaled
      allergen.

PMID- 8564097
TI  - Hypothalamic-pituitary-adrenal axis in corticosteroid-resistant bronchial asthma.
AB  - We have examined whether the lack of clinical response to corticosteroids seen in
      corticosteroid resistant (CR) bronchial asthma is reflected in abnormalities of
      endogenous cortisol secretion and in the sensitivity of the hypothalamic
      pituitary-adrenal (HPA) axis in CR subjects by using a modification of the
      standard dexamethasone suppression test (DST) in response to 0.25 and 1 mg oral
      dexamethasone. Five corticosteroid-sensitive (CS) and five CR asthmatic subjects
      were studied on two occasions 1 mo apart. In the first limb of the study subjects
      received 0.25 mg of oral dexamethasone, and in the second limb they received 1
      mg. Urinary cortisol was measured by fluorimetry after extraction, and plasma
      cortisol and adrenocorticotropic hormone (ACTH) concentrations were estimated by
      enzyme-linked immunosorbent assay (ELISA) and immunoradiometric assays,
      respectively. On Day 1, a 24-h urine sample was collected for estimation of
      urinary free cortisol. On Day 2, a fasting blood sample was taken at 9:00 A.M.
      for estimation of plasma cortisol and ACTH. At 11:00 P.M., 0.25 mg (1 mg) of
      dexamethasone was taken orally by each subject. On Day 3, blood was taken at 9:00
      A.M. and 3:00 P.M. for similar estimations. The levels of urinary free cortisol
      (nmol/24 h) and predose plasma ACTH (ng/L) and cortisol (nmol/L) were 199 +/- 42,
      27.4 +/- 5.7, and 300 +/- 48 (mean +/- SEM), respectively, in the CS group, and
      210 +/- 74, 23.4 +/- 6.7, and 263 +/- 32 (mean +/- SEM), respectively, in the CR
      group (p > 0.05 for all comparisons). Plasma ACTH and cortisol concentrations
      were not significantly suppressed in either group after 0.25 mg dexamethasone,
      but were equally suppressed in both groups to undetectable levels by 1 mg
      dexamethasone. We conclude that CR asthma is not reflected in an altered
      secretory rate of endogenous cortisol or in an altered sensitivity of the HPA
      axis to dexamethasone suppression.

PMID- 8564096
TI  - Prednisolone treatment in asthma. Reduction in the numbers of eosinophils, T
      cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5, and
      interferon-gamma cytokine gene expression within the bronchial mucosa.
AB  - We have tested the hypothesis that the beneficial effects of corticosteroids in
      asthma may result from reduction in the number of inflammatory cells infiltrating
      the bronchial mucosa with inhibition of cytokine gene expression. A randomized
      parallel group study was performed in 18 moderately severe asthmatic patients in
      whom an elective trial of corticosteroid treatment was indicated. Fiberoptic
      bronchoscopy was performed and bronchial biopsies taken from segmental carinae
      before and after 2 wk treatment with prednisolone (0.6 mg/kg/d) or matched
      placebo tablets. Immunohistology was performed on 6-microns cryostat sections
      using monoclonal antibodies. The number of cells expressing cytokine messenger
      RNA (mRNA) was assessed by in situ hybridization using S35-labeled riboprobes.
      When prednisolone- and placebo-treated groups were compared there was a decrease
      in airway methacholine responsiveness (p < 0.01) and an increase in FEV1 (p <
      0.05) after prednisolone. This was accompanied by a reduction in CD3+ T
      lymphocytes (p < 0.05), "activated" EG2+ eosinophils (p < 0.02), and tryptase
      only (mucosal-type) MCT cells (p < 0.02) but not MCTC (tryptase+chymase positive)
      cells in prednisolone-treated patients. In prednisolone-treated patients there
      was also a reduction in the number of cells expressing mRNA for interleukin-4 (IL
      4, p < 0.01), and interleukin-5 (IL-5, p < 0.03) and an increase in cells
      expressing mRNA for interferon-gamma (IFN-gamma) (p < 0.01). These results
      support the view that corticosteroid treatment in asthma may act by modulation of
      cytokine expression with consequent inhibition of the local bronchial
      inflammatory infiltrate and tissue eosinophilia.

PMID- 8564098
TI  - Skin test reactivity to common aeroallergens and decline of lung function. The
      Normative Aging Study.
AB  - It has been hypothesized that allergy is associated with an increased risk of
      developing chronic irreversible airflow obstruction. We have investigated the
      relation between immediate cutaneous hypersensitivity to common aeroallergens and
      the subsequent rate of decline of lung function in 1,025 men participating in the
      Normative Aging Study; subjects had a mean age of 61 +/- 8 (SD) yr and denied any
      history of asthma. Subjects performed spirometry and underwent allergen skin
      testing at a baseline visit and performed repeat spirometry after a median of 3.1
      yr. Skin prick tests were performed using four glycerin-preserved allergens
      (house dust, mixed grasses, mixed trees, and ragweed); wheal size was measured at
      20 min. Multiple linear regression analysis was used to examine the annual rate
      of change of lung function in relation to skin test reactivity, defined as a mean
      wheal size to the 4 allergens > or = 2 mm, after adjustment for age, height,
      smoking status, and initial lung function. Skin test reactivity was a significant
      predictor of the annual rates of decline of FEV1 and FEV1/FVC ratio. The
      regression model predicted an excess decline of FEV1 of 9.45 ml/yr for subjects
      with mean wheal diameter > or = 2 mm (p < 0.05); the excess rate of decline of
      FEV1/FVC ratio was 0.29 percent/yr (p = 0.001). There was no significant relation
      between mean wheal diameter and rate of decline of FVC. The magnitude of the
      effects of a mean wheal diameter > or = 2 mm on rates of decline of FEV1 and
      FEV1/FVC ratio are 34% and 49%, respectively, of the magnitude of the effects of
      current cigarette smoking in these models. We conclude that cutaneous
      hypersensitivity to common aeroallergens is a significant independent predictor
      of subsequent decline of lung function among middle-aged and older men with no
      history of asthma.

PMID- 8564099
TI  - Protective and bronchodilator effects of prostaglandin E and salbutamol in
      aspirin-induced asthma.
AB  - We performed a double-blind, two-phase study on protective and bronchodilator
      effects of prostaglandins E2 and E1 (PGE2, PGE1) and salbutamol in patients with
      aspirin-induced asthma (AIA). In phase 1 we assessed the effects of pretreatment
      with PGE2, salbutamol, or the PGE1-analogue, misoprostol, on bronchoconstriction
      precipitated by inhalation of L-lysine aspirin in 11 patients with AIA. PGE2 and
      salbutamol were inhaled at equimolar concentrations of 0.25 mumol, 5 min before
      the aspirin challenge, while 400 micrograms misoprostol was administered orally 1
      h before challenge. PGE2 attenuated the bronchoconstrictive reactions in 10
      patients, salbutamol in eight, and misoprostol in seven. The mean provocative
      dose of aspirin causing a 20% fall in FEV1 (PD20) decreased after PGE2 (p = 0.04)
      and salbutamol (p = 0.06), but only marginally after misoprostol (p = 0.25).
      There was a positive correlation between magnitude of the protection offered by
      the three compounds in individual subjects. In phase 2, we examined bronchial
      response to inhaled PGE2, PGE1, salbutamol, and 2% ethanol in 12 AIA patients
      compared with 10 aspirin-tolerant patients with asthma. AIA subjects were
      characterized by less pronounced and shorter bronchodilator responses. There was
      no correlation between the protective and bronchodilator actions of the compounds
      used in individual patients. Thus, inhaled PGE2 and salbutamol protect against
      aspirin-induced attacks of asthma through mechanisms unrelated to their
      bronchodilator properties. Airways of aspirin-sensitive patients with asthma
      demonstrate distinct bronchial reactivity.

PMID- 8564100
TI  - Inhaled PGE2 prevents aspirin-induced bronchoconstriction and urinary LTE4
      excretion in aspirin-sensitive asthma.
AB  - Bronchial overproduction of leukotrienes and inhibition of prostaglandin
      synthesis are involved in the pathogenesis of aspirin-induced asthma. We
      investigated whether inhaled prostaglandin E2 (PGE2) attenuates the response to
      bronchial challenge with lysine acetylsalicylate (LASA) and the associated
      increase in urinary leukotriene E4 (u-LTE4) in seven aspirin-sensitive subjects
      with asthma. Each subject performed two challenges with a single dose of LASA
      that caused a decrease in FEV1 of 20% or more in a preliminary test, immediately
      after inhaling 100 micrograms PGE2 in 4 ml saline or placebo, according to a
      randomized double-blind protocol. FEV1 was recorded at 30-min intervals for 4 h.
      u-LTE4 was measured by combined high-performance liquid chromatography enzyme
      immunoassay at 2-h intervals. After placebo, LASA caused an obstructive reaction
      in all patients, with a maximum decrease in FEV1 of 35 +/- 5% with respect to
      baseline. u-LTE4 rose from 911 +/- 261 picograms (pg)/mg creatinine at baseline
      to a maximum value of 2249 +/- 748 after challenge. Inhaled PGE2 provided almost
      complete protection in all patients. Baseline u-LTE4 was 883 +/- 243 pg/mg
      creatinine and did not change significantly during the test, reaching a maximum
      value of 864 +/- 290 (p < 0.05 versus placebo). These results confirm that PGE2
      is highly effective in preventing aspirin-induced asthma and suggest that this
      effect is mediated by inhibition of sulfidopeptide leukotriene production.

PMID- 8564101
TI  - Beta 2-agonist treatment reduces beta 2-sensitivity in alveolar macrophages
      despite corticosteroid treatment.
AB  - Alveolar macrophage beta 2-adrenoceptor sensitivity and bronchodilator responses
      to inhaled terbutaline were investigated before and after 2 wk of oral treatment
      with terbutaline 7.5 mg twice a day in healthy volunteers. The influence of
      corticosteroid treatment was examined by giving 10 subjects budesonide 400
      micrograms twice a day by inhalation throughout the treatment period, and by
      giving 10 subjects 40 mg prednisolone and 10 subjects placebo orally 12 h before
      the second examination. Terbutaline treatment elicited marked attenuation
      (approximately 75% reductions) of isoprenaline-induced cyclic AMP accumulation in
      the alveolar macrophages. Responses to prostaglandin E1 were not influenced by
      treatment, suggesting homologous beta-adrenoceptor desensitization.
      Corticosteroid administration failed to either prevent (budesonide) or reverse
      (prednisolone) this desensitization. Bronchodilator responses to terbutaline were
      not altered by treatment in either group. We conclude that the beta 2
      adrenoceptor sensitivity of human alveolar macrophages is markedly and
      selectively depressed by beta 2-agonist treatment and that corticosteroid
      treatment, contrary to previous hypotheses, fails to influence this phenomenon.
      Studies on the mechanisms involved are needed. The importance of alveolar
      macrophages in asthma is unclear, but the present data in humans are of interest
      in relation to possible effects of continuous beta 2-agonist treatment on
      inflammatory mechanisms in the airways.

PMID- 8564102
TI  - Detection of excessive bronchoconstriction in asthma.
AB  - Airway hyperresponsiveness is easily assessed by measuring the concentration or
      dose of an inhaled agonist that produces a defined response, e.g., PC20 or PD20.
      However, this measure does not assess excessive bronchoconstriction. We report
      the results of analyzing bronchial dose-response curves by measuring percent fall
      in vital capacity (delta FVC%) as the response rather than the PC20. In our
      analysis, delta FVC% was measured at the PC20, and therefore it was the dependent
      variable, whereas the concentration of agonist was the independent variable, in
      contrast to the usual bronchoprovocation tests in which the response is the
      independent variable and the dose is the dependent variable. We reasoned that a
      dose-dependent increase in gas trapping with histamine would detect excessive
      bronchoconstriction as a decrease in FVC; in contrast, PC20 measures only the
      ease of bronchoconstriction. In 10 patients with mild asthma the reproducibility
      of delta FVC% when FEV1 fell by 20%, i.e., at the PC20 concentration of
      histamine, taken from a greater than 6-s FVC on an otherwise standard histamine
      challenge test was comparable to that of PC20. In 10 healthy asymptomatic
      subjects there were only trivial falls (0.3%) in FVC to as much as 16 mg/ml
      histamine. In a retrospective study of 146 patients with mild asthma, the delta
      FVC% was normally distributed (13.2 +/- 5.5 SD%) and did not correlate with the
      number of beta 2-agonist prescriptions or the PC20, but it did correlate with the
      number of prescriptions written per month for oral prednisone (r = 0.55, p <
      0.02). We conclude that delta FVC% when FEV1 falls by 20% is a safe method of
      detecting excessive bronchoconstriction, and it reveals that different asthmatics
      react in fundamentally different ways to the same agonist. This may be useful in
      detecting the asthmatic at risk for serious disease.

PMID- 8564103
TI  - 8-Epi-PGF2 alpha, a novel noncyclooxygenase-derived prostaglandin, constricts
      airways in vitro.
AB  - 8-Epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) is an F2-isoprostane formed via a
      noncyclooxygenase pathway. We investigated whether 8-epi-PGF2 alpha has any
      effects on isolated guinea-pig and human airway smooth-muscle tone, and
      characterized the receptor involved in these effects. Cumulative concentration
      responses to 8-epi-PGF2 alpha in the absence or presence of prostanoid TP- and
      EP1-receptors antagonists (ICI 192, 605 and AH 6809, respectively) were compared
      with the responses to U46619 (a thromboxane A2 mimetic) and PGF2 alpha. 8-epi
      PGF2 alpha contracted airway smooth muscle with a rank order of potency of U46619
      > PGF alpha > 8-epi-PGF2 alpha for guinea pig and U46619 > 8-epi-PGF2 alpha >
      PGF2 alpha for human smooth muscle. ICI 192,605 inhibited guinea-pig tracheal
      contraction produced by U46619 (pA2 = 10.0) with a similar potency to its
      inhibition of the contraction induced by 8-epi-PGF2 alpha (apparent pKB = 10.2,
      10.3), but not that induced by PGF2 alpha (apparent pKB = 6.6). AH 6809 inhibited
      contraction induced by PGF2 alpha (pA2 = 6.6) with a greater potency than
      contraction induced by U46619 (apparent pKB = 5.1, 5.2) or 8-epi-PGF2 alpha
      (apparent pKB = 5.3). In human airways, ICI 192,605 inhibited contraction induced
      by U46619 and 8-epi-PGF2 alpha with apparent pKB values of 9.5 and 9.4,
      respectively, and AH 6809 inhibited contraction induced by 8-epi-PGF2 alpha with
      apparent pKB values of 5.7 and 5.4. We conclude that 8-epi-PGF2 alpha contracts
      human and guinea-pig airways via prostanoid TP receptors. However, if 8-epi-PGF2
      alpha is formed in asthma, its production, unlike that of other prostanoids,
      would not be inhibited by cyclooxygenase inhibitors.

PMID- 8564104
TI  - Airway reactivity changes in asthmatic patients undergoing blinded food
      challenges.
AB  - To investigate the possible pathogenic role of food allergy in asthma, airway
      hyperresponsiveness was measured by methacholine inhalation challenges (MIC)
      performed before and after double-blind, placebo-controlled food challenges
      (DBPCFC) in 26 food-allergic, asthmatic patients. Airway hyperresponsiveness was
      classified as severe in two cases (PD20FEV1 < 2 breath units, BU), moderate in 18
      (PD20FEV1: 2-20 BU), and mild in six (PD20FEV1 > 20 BU). Medications included
      albuterol (81%), inhaled steroids (38%), cromolyn (35%), and theophylline (23%).
      MICs were performed in the afternoon after DBPCFC. Of the 22 positive DBPCFC, 12
      involved chest symptoms (cough, wheezing, or both). Another 10 positive DBPCFCs
      included laryngeal, gastrointestinal, and/or skin symptoms without any chest
      symptoms. Significant increases in airway hyperresponsiveness were evident in
      seven of 12 patients experiencing chest symptoms during DBPCFC. Significant
      increases in airway hyperresponsiveness were observed in one patient without
      chest symptoms during a positive DBPCFC and one patient after a negative DBPCFC.
      However, this last patient had a negative MIC with the same antigen 1 yr later.
      These studies indicate that food-induced allergic reactions can increase airway
      reactivity, and may do so without inducing acute asthma.

PMID- 8564105
TI  - Inhaled nitric oxide attenuates bronchoconstriction in canine peripheral airways.
AB  - Inhaled nitric oxide has been proposed as a bronchodilator because it relaxes
      vascular and airway smooth muscle and attenuates cholinergic reflexes. Although
      inhaled nitric oxide has been shown to act as a bronchodilator in central
      airways, effects on peripheral airways are largely unknown. To determine whether
      nitric oxide produces direct relaxation of peripheral airways, we investigated
      the ability of nitric oxide to attenuate hypocapnia- and acetylcholine-induced
      constriction in the peripheral airways of anesthetized dogs. Peripheral airway
      resistance (RP) was measured using a wedged bronchoscope technique. RP was
      increased by either hypocapnia (0% CO2 through the bronchoscope for 3 min) or by
      aerosolized acetylcholine (30 to 60 micrograms/ml for 1 to 3 min), in the
      presence or absence of nitric oxide. Nitric oxide was delivered directly to the
      lung periphery in the absence of O2. Nitric oxide (14.5 to 250 ppm) attenuated
      responses to hypocapnia by 38 +/- 0 to 74 +/- 0% (n = 6) and to acetylcholine by
      36 +/- 0 to 52 +/- 0% (n = 6). The ability of inhaled nitric oxide (< 100 ppm) to
      attenuate Rp responses to two different direct-acting stimuli suggests that
      nitric oxide acts as a bronchodilator in the lung periphery. The mechanism for
      this effect may involve relaxation of airway and/or vascular smooth muscle.

PMID- 8564106
TI  - Inspiratory muscle strength and endurance in steroid-dependent asthma.
AB  - The adverse effect of long-term steroid treatment on respiratory muscle function
      remains controversial. We evaluated inspiratory muscle strength and endurance in
      steroid-dependent asthmatics in comparison with other asthmatics or with patients
      with chronic obstructive pulmonary disease exhibiting a comparable level of lung
      hyperinflation. Inspiratory muscle function was assessed by maximal inspiratory
      pressure (Pimax) and by an incremental inspiratory threshold loading test in 19
      patients who had had steroid-dependent asthma (SDA) requiring a mean daily dose
      of 20.7 +/- 0.8 mg prednisone for 5 +/- 1.4 yr. They were compared with 16
      healthy control subjects, 30 patients with COPD, and 16 patients with non-steroid
      dependent asthma (NSDA). Pimax as percentage of predicted values (%Pimax) was not
      significantly different in patients with SDA (77 +/- 5%) or NSDA (83 +/- 6%) than
      in control subjects (93 +/- 4%). In contrast, %Pimax was lower in patients with
      COPD (59 +/- 4.4%) than in those with SDA or NSDA (p < 0.05) or the control
      subjects (p < 0.0001). A significant correlation was found between %Pimax and
      hyperinflation assessed by the FRC/TLC ratio (r = 0.42; p < 0.001). Inspiratory
      endurance, defined as the ratio of maximal peak inspiratory pressure sustained
      for 2 min to individual Pimax (Plim2/Pimax), was significantly lower in the SDA
      (43 +/- 3%; p < 0.0001), NSDA (65 +/- 4%; p = 0.01), and COPD (55 +/- 3%; p <
      0.0001) groups than in the control group (76 +/- 2%). Plim2/Pimax was also lower
      in patients with SDA than in those with COPD (p = 0.0073) or NSDA (p < 0.0001).
      Hyperinflation plays a major role in inspiratory muscle dysfunction associated
      with obstructive lung disorders, but the finding of a significantly decreased
      endurance in patients with SDA when compared with patients with COPD, despite a
      lower level of hyperinflation in the former group, points to a deleterious effect
      of long-term corticosteroid treatment on inspiratory muscle function in
      asthmatics.

PMID- 8564108
TI  - Discharge frequencies of parasternal intercostal and scalene motor units during
      breathing in normal and COPD subjects.
AB  - To determine whether patients with chronic obstructive pulmonary disease (COPD)
      contract the inspiratory muscles of the rib cage more strongly than do healthy
      subjects, we recorded the discharge frequencies of single motor units in the
      scalene and second parasternal intercostal muscles of seven patients with stable
      COPD (FEV1 = 33 +/- 13% predicted, mean +/- SD) and seven control subjects.
      Recordings were made with insulated monopolar electrodes during resting
      breathing, and single motor-unit discharges were identified with a customized
      method based on "template" matching. A total of 211 motor units were recorded in
      the control subjects and 260 in the patients. The inspiratory discharge
      frequencies were greater in the COPD patients than in the control subjects for
      both the parasternal (13.4 versus 10.1 Hz, p < 0.05) and scalene (11.4 versus 8.5
      Hz, p < 0.02) muscles. Recording sites at which no motor units were recruited
      were more common in the control subjects than in the patients (p < 0.001). The
      sternomastoid muscle was silent in both subject groups. Therefore, effective
      central neural drive is increased to both the scalene and parasternal intercostal
      muscles but not to the sternomastoid muscle in patients with COPD.

PMID- 8564107
TI  - Effect of fluticasone propionate on sputum of patients with chronic bronchitis
      and emphysema.
AB  - The effects of fluticasone propionate (FP) on sputum chemotactic activity,
      elastase inhibitory potential, albumin concentrations, and peripheral neutrophil
      function were studied in a group of patients with clinically stable, smoking
      related chronic bronchitis and emphysema. Seventeen patients (50 to 75 yr of age)
      were entered into a double-blind, placebo-controlled study of 1.5 mg inhaled FP/d
      for 8 wk. Following treatment with FP the chemotactic activity of the sputum sol
      phase was lower than the corresponding values for the placebo group (p < 0.01).
      Values fell from a mean of 21.75 (+/- 1.58) during the run-in period to 18.37 (+/
      1.46; p < 0.01) after 4 wk and 17.63 (+/- 1.86; p < 0.05) after 8 wk treatment
      returning to 22.08 (+/- 1.26) cell/field after the washout period. The neutrophil
      elastase inhibitory capacity of the sputum sol phase increased (p < 0.025) with
      treatment from a mean of 0.177 microM elastase inhibited/L (+/- 0.05)
      pretreatment to 0.413 microM (+/- 0.054) after 4 wk and 0.415 microM (+/- 0.054)
      after 8 wk returning to 0.270 microM (+/- 0.07) after the washout period.
      Treatment with FP did not result in a change in the peripheral neutrophil
      functions studied or sputum albumin and myeloperoxidase concentrations. The
      results suggest that FP may play a protective role in these patients through a
      reduction in the chemotactic activity of lung secretions and potentially a
      reduction in the recruitment of neutrophils to the lung, and also by directly
      affecting the proteinase/antiproteinase balance, in favor of antiproteinases,
      within lung secretions.

PMID- 8564109
TI  - Airflow limitation in chronic bronchitis is associated with T-lymphocyte and
      macrophage infiltration of the bronchial mucosa.
AB  - To investigate whether the airway inflammatory process is different in patients
      with chronic bronchitis with airflow limitation and those with chronic bronchitis
      without airflow limitation, we obtained bronchial biopsies from 14 subjects with
      chronic sputum production and fixed airway obstruction, and from 10 subjects with
      chronic sputum production and normal FEV1, all with a history of cigarette
      smoking. Paraffin-embedded and frozen bronchial biopsies were examined by
      immunohistochemistry to identify the number of neutrophils (neutrophil-elastase),
      eosinophils (antieosinophil cationic protein [EG-2]), mast cells (tryptase), T
      lymphocytes (CD3), T-lymphocyte subpopulations (CD4 and CD8), B-lymphocytes, and
      macrophages (CD68) in the submucosa. Subjects with chronic bronchitis with
      airflow limitation had a greater number of T-lymphocytes (p < 0.01) and
      macrophages (p < 0.05) than subjects with chronic bronchitis without airflow
      limitation, whereas the T-lymphocyte subpopulations and the numbers of B
      lymphocytes, neutrophils, eosinophils, and mast cells were similar in the two
      groups. When all the subjects were considered together, the number of T
      lymphocytes correlated inversely with the values of FEV1 (r = 0.46, p < 0.02). In
      conclusion, airflow limitation in subjects with chronic bronchitis is associated
      with an increased number of T-lymphocytes and macrophages in the bronchial
      mucosa.

PMID- 8564110
TI  - Elevated TNF-alpha production by peripheral blood monocytes of weight-losing COPD
      patients.
AB  - The inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1-beta (IL-1 beta), have been associated with accelerated metabolism
      and protein turnover following exogenous administration in normal humans. We
      hypothesized that these inflammatory cytokines might contribute to the weight
      losing process in patients with chronic obstructive pulmonary disease (COPD).
      COPD patients were identified prospectively as "weight losers" (WL; n = 10) if
      they reported > 5% weight loss during the preceding year or as "weight stable"
      (WS; n = 10) if their body weight fluctuated < or = 5%. Age-matched healthy
      volunteers were selected as the control group (C; n = 13). Monocytes were
      isolated from a peripheral blood sample, cultured, and exposed to
      lipopolysaccharide (LPS). The concentration of TNF-alpha and IL-1 beta in the
      monocyte supernatant was measured using a four layer enhanced ELISA. No
      significant difference in LPS-stimulated IL-1 beta production was found in the
      three study populations. However, LPS-stimulated TNF-alpha production (mean
      [range] ng/ml) by monocytes was significantly higher in the WL COPD patients
      (20.2 [6.3 to 44.8]), compared with WS patients (6.9 [1.5 to 16.6]), and C
      subjects (5.7 [0 to 61.8]). This difference was not maintained at 6 mo follow-up
      in the absence of ongoing weight loss. Definition of a causal relationship
      between TNF-alpha production and weight loss will require further understanding
      of the relationship between energy metabolism and TNF-alpha production in these
      patients.

PMID- 8564111
TI  - Morphologic aspects of airways of patients with pulmonary emphysema followed by
      bronchial asthma-like attack.
AB  - Morphometric analysis of airways was performed in autopsied lungs from four
      patients with pulmonary emphysema (PE) followed by bronchial-asthma (BA)-like
      attacks (Group PE+BA) (four males, 72 +/- 9 yr). The results were compared with
      those from five pulmonary emphysema patients (Group PE) (five males, age 71 +/- 4
      hr), three patients with bronchial asthma (Group BA) (one female and two males,
      age 65 +/- 7 yr), and four control subjects with no pulmonary diseases (Group
      Cont) (one female, three males, age 64 +/- 4 yr). The proportion of gland area to
      bronchial wall (gland%), ratio of goblet-cell occupancy to the total epithelial
      layer (goblet%), thickness of the basement membrane, amount of intraluminal mucus
      (mucus occupying ratio; MOR%), and number of various cell types per square
      millimeter in airway walls in a section 4 microns thick were measured in central
      (3 to 8 mm diameter) and peripheral airways (2 mm or less diameter). Gland% for
      the PE+BA group was significantly greater than that for the Cont group, whereas
      it did not differ significantly from that of the PE or BA groups. Goblet% and
      thickness of the basement membrane in central and/or peripheral airways in Group
      PE+BA were significantly greater than those in Group Cont, whereas those in Group
      PE were similar to those in Group Cont. Although not statistically significant,
      MOR% in central and peripheral airways from Group PE+BA showed a similar value to
      that in Group BA, whereas MOR% in Group PE was the same as that in Group Cont.
      The eosinophil number in peripheral airways walls in Group PE+BA showed a similar
      value to that in Group BA, which was significantly greater than in Group Cont.
      Other cells (macrophages, lymphocytes, and neutrophils) showed similar values
      among Groups PE+BA, PE, and BA. The number of eosinophils in central and/or
      peripheral airways correlated significantly with both goblet% and BMT, whereas
      other cells did not. These findings indicate that the airways of Group PE+BA are
      morphologically similar to those of Group BA, suggesting a combination of
      pulmonary emphysema with bronchial asthma.

PMID- 8564112
TI  - Mineral dusts cause elastin and collagen breakdown in the rat lung: a potential
      mechanism of dust-induced emphysema.
AB  - It is now accepted that workers with exposure to mineral dusts can develop
      airflow obstruction. The basis of this process is uncertain, but carefully
      performed morphologic studies suggest that coal, silica, and perhaps other dusts
      may produce emphysema in humans. To investigate the mechanisms involved in this
      process, we administered crystalline silica (quartz) or titanium dioxide (rutile)
      to rats in a single intratracheal instillation. At varying times after
      instillation, the animals' lungs were lavaged, the lavageate from one lung was
      dried and hydrolyzed, and the amounts of desmosine (DES),as a measure of elastin
      breakdown, and hydroxyproline (HP), as a measure of collagen breakdown, were
      determined. The lavageate from the other lung was counted for inflammatory cells.
      Both silica and titanium dioxide caused a dose-dependent increase in DES and HP
      24 h after instillation. When an equivalent dose (30 mg) of silica or rutile was
      administered and animals were sacrificed at various times up to 21 d, a sustained
      increase in lavage DES and HP was seen in the silica-treated animals, and this
      was accompanied by a sustained increase in polymorphonuclear leukocytes (PMN); in
      contrast, both lavage PMN and lavage DES/HP rapidly peaked and then declined in
      the titanium dioxide-treated animals. Numbers of macrophages remained elevated
      over the 21-d period of sacrifice with both types of treatment. These data show
      for the first time that mineral dusts can cause connective-tissue breakdown in
      the lung, with the release of matrix components into the alveolar spaces. The
      amount of connective-tissue breakdown appears to parallel the number of PMN but
      not the number of macrophages in the alveolar spaces, suggesting that PMN-derived
      proteolytic enzymes are responsible for the breakdown. This process probably
      plays a role in dust-induced emphysema.

PMID- 8564113
TI  - IgG subclass deficiencies associated with bronchiectasis.
AB  - Only a small number of patients with IgG subclass deficiencies (IgGSD) have been
      observed to have bronchiectasis. Moreover, in the series of patients with
      bronchiectasis, IgGSD have not been found at any frequency, and the etiology of
      bronchiectasis remains unclear in 29 to 49% of cases. Serum concentrations of
      total IgG, IgA, and IgG subclasses as well as pulmonary function were measured in
      65 patients (aged: 10 to 74 yr) with bronchiectasis of unknown etiology. An ELISA
      test was performed to quantify subclasses 1 through 4 using subclass-specific
      antihuman monoclonal antibodies. IgG subclass estimation in a healthy population
      with age-stratified normal ranges was derived from 100 adults, 37 children aged
      between 10 and 12 yr, and 27 adolescents aged between 13 and 16 yr. Serum
      concentrations of specific IgG antibodies to Haemophilus influenzae type b
      capsular polysaccharide (Hib-PRP) were also assayed by an ELISA test in 19 of the
      patients (10 with IgGSD and nine with non-IgGSD) and in 58 healthy individuals
      before and 3 wk after immunization with Hib-PRP conjugated to meningococcal outer
      membrane protein complex (OMPC). Thirty-one patients (48%) had low serum
      concentrations of one or more IgG subclasses (19 IgG2 deficiencies, 2 IgG3
      deficiencies, 3 IgG4 deficiencies, and 7 combined subclass deficiencies). All
      patients showed increased levels of total IgG, IgG1, and IgA, but this rise was
      significantly higher in patients without IgGSD. Patients with IgGSD showed
      impaired antibody response to Hib-PRP compared with patients with non-IgGSD and
      the control group. IgGSD, particularly IgG2 deficiency, are not an unusual cause
      of bronchiectasis. Therefore, serum levels of IgG subclasses must be assayed
      whenever other causes of bronchiectasis have been ruled out.

PMID- 8564114
TI  - The determinants of pulmonary diffusing capacity in a national sample of U.S.
      adults.
AB  - Racial and gender differences in single-breath pulmonary diffusing capacity for
      carbon monoxide (DLCO) have previously received little attention. Between 1971
      and 1975, the first National Health and Nutrition Examination Survey determined
      DLCO for 4,439 adults ages 25 to 74 residing in the United States, including
      2,345 women and 438 blacks. The large sample permitted an evaluation of
      interactions and nonlinear relationships with DLCO, and its association with
      biomarkers of inflammation. In a model with separate race, sex, and smoking
      status intercepts, positive associations with FVC, height, weight, hemoglobin
      concentration, and negative associations with age and neutrophil count explained
      59% of the variation in DLCO. In women, the decline in DLCO with age was much
      less than in men, but after age 47 the decline with age approached that seen in
      men. Blacks had lower DLCO levels (-1.96 ml/min/mm Hg, 95% confidence interval
      [CI] -0.77 to -3.14) with or without adjustment for FVC, but the changes in DLCO
      with age and height were similar in both races. Former smokers had lower DLCO (
      1.13 ml/min/mm Hg, 95% CI -1.57 to -0.69), but this reduction was fully explained
      by the number of pack-years smoked. In current smokers, cigarettes per day and
      pack-years were predictive of DLCO even after control for FVC and controlling for
      these variables fully explained the difference in DLCO between never and current
      smokers. Peripheral neutrophil count, a biomarker of inflammation, was associated
      with reduced DLCO. Thus, substantial sex and race differences exist for DLCO
      within the general United States population.

PMID- 8564116
TI  - Effects of ventilator resistance and compliance on phrenic nerve activity in
      spontaneously breathing cats.
AB  - This study investigates the effects of respiratory mechanical loading and
      unloading on phrenic nerve activity and ventilation. Ten adult cats were
      anesthetized, intubated, and connected to a servocontrolled infant ventilator
      while breathing spontaneously in continuous positive airway pressure mode. The
      ventilator was then set to decrease the pressure at the airway opening in
      proportion to the inspiratory airflow or the volume of spontaneous breathing
      (resistive or elastic loading) or to increase the pressure at the airway opening
      accordingly (resistive or elastic unloading, also called proportional assist
      ventilation). When compared with continuous positive airway pressure, both
      resistive and elastic loading increased the number of phrenic nerve impulses per
      breath and the mean frequency of impulses (p < 0.01, ANOVA). In contrast, elastic
      unloading decreased phrenic nerve activity significantly in normal and injured
      lungs. Resistive unloading in normal lungs did not change phrenic nerve activity
      significantly. The compensatory response in phrenic nerve activity was not large
      enough to completely offset effects of loading and unloading on ventilation:
      elastic and resistive loading decreased ventilation. Unloading had the opposite
      effect on ventilation, particularly in injured lungs. We conclude that
      respiratory mechanical loading and unloading have statistically significant,
      opposite effects on phrenic nerve activity and opposite effects on ventilation.

PMID- 8564115
TI  - Surfactant treatment before reperfusion improves the immediate function of lung
      transplants in rats.
AB  - An impaired function of alveolar surfactant can cause lung transplant dysfunction
      early after reperfusion. In this study it was investigated whether treatment with
      surfactant before reperfusion improves the immediate function of lung transplants
      and whether an improved transplant function was associated with an increase in
      alveolar surfactant components. Left lungs with 6-h (n = 8) or prolonged 20-h
      ischemia (n = 10) were transplanted syngeneically in rats. In both ischemia
      groups half of the lung transplants were treated with surfactant just before
      reperfusion. Lung function was measured during reperfusion for 1 h. Thereafter,
      the rats were killed and bronchoalveolar lavage was performed to measure alveolar
      surfactant components. We found that surfactant treatment improved the immediate
      function of lung transplants in parallel with a higher amount of total surfactant
      phospholipids, a higher percentage of the heavy subtype of surfactant, a
      normalized percentage of phosphatidylcholine, and a higher amount of endogenous
      surfactant protein A (SP-A). We conclude that surfactant treatment before
      reperfusion does improve the immediate lung transplant function in rats in
      association with an increase in alveolar surfactant components. More
      particularly, the amount of (endogenous) SP-A is thought to be crucial for the
      efficacy of surfactant treatment after lung transplantation.

PMID- 8564117
TI  - Does plasma protein depletion increase lung liquid conductance?
AB  - Lung liquid conductance (Kf) is calculated as the quotient of lung lymph flow
      divided by net filtration pressure (Pnf), where Pnf is the balance of osmotic and
      hydrostatic pressures in the lung microcirculation. In protein depletion, lymph
      flow rises with little change in Pnf, suggesting that calculated Kf also rises.
      However, several previous reports have concluded that protein depletion causes
      little change in Kf, leaving open the question of how lung lymph flow can rise in
      protein depletion with little change in Pnf. To address this, we measured Kf in
      sheep following two kinds of protein depletion: batch plasmapheresis (BP; n = 5)
      and thoracic duct drainage (TD; n = 5). Both methods lowered plasma protein
      concentrations by 30%, and raised lung lymph flows by 55%. Lung microvascular
      hydrostatic pressures and plasma-to-lymph osmotic pressure gradients both changed
      by 1 to 2 mm Hg. With BP, calculated Kf rose from 0.26 +/- 0.09 at baseline to
      0.50 +/- 0.20 on Day 1, and to 0.39 +/- 0.27 ml/mm Hg/30 min on Day 2 (p < or =
      0.05). With TD, calculated Kf rose from 0.28 +/- 0.13 at baseline to 0.43 +/-
      0.19 on Day 1, and to 0.43 +/- 0.19 ml/mm Hg/30 min on Day 2 (p < or = 0.05).
      Calculated Kf rose because filtration increased even though the hydrostatic and
      osmotic driving forces responsible for filtration changed little. This is
      puzzling because it suggests that lymph flow rose with little or no change in the
      forces affecting filtration. Our findings contradict several previous reports
      that concluded that protein depletion produces little or no change in calculated
      Kf.

PMID- 8564118
TI  - Bedside prediction of mortality from bacteremic sepsis. A dynamic analysis of ICU
      patients.
AB  - The prognosis in patients with sepsis depends on severity of acute illness,
      underlying chronic diseases, and complications associated with infection.
      Adjusting for these factors is essential for evaluation of new therapies. The
      purpose of the present study was to determine variables readily identifiable at
      the bedside that predict mortality in intensive care unit (ICU) patients with
      sepsis and positive blood cultures. For a 5-yr period, all patients of a surgical
      ICU presenting with positive blood cultures and sepsis were systematically
      analyzed for clinical variables and organ dysfunctions at the day of onset of
      sepsis and bacteremia and during the subsequent clinical course. The prognostic
      value of these variables was determined using logistic regression procedures. Of
      the 5,457 admissions to the ICU, 176 patients developed sepsis with positive
      blood cultures (3.2 per 100 admissions). The fatality rate was 35% at 28 days
      after the onset of sepsis; in-hospital mortality was 43%. Independent predictors
      of mortality at onset of sepsis were previous antibiotic therapy (odds ratio
      [OR], 2.40; 95% confidence interval [CI95], 1.59 to 3.62; p = 0.034), hypothermia
      (OR, 1.43; CI95, 1.04 to 2.44; p = 0.030), requirement for mechanical ventilation
      (OR, 2.97; CI95, 1.96 to 4.51; p = 0.009), and onset-of-sepsis APACHE II score
      (OR, 1.21; CI95, 1.13 to 1.29; p < 0.001). Vital organ dysfunctions developing
      after the onset of sepsis influenced outcome markedly. The best two independent
      prognostic factors were the APACHE II score at the onset of sepsis (OR, 1.13 per
      unit; CI95, 1.08 to 1.17; p = 0.0016) and the number of organ dysfunctions
      developing thereafter (OR, 2.39; CI95, 2.02 to 2.82; p < 0.001). In ICU patients
      with sepsis and positive blood cultures, outcome can be predicted by the severity
      of illness at onset of sepsis and the number of vital organ dysfunctions
      developing subsequently. These variables are easily assessed at the bedside and
      should be included in the evaluation of new therapeutic strategies.

PMID- 8564119
TI  - Development and validation of a technique for continuous monitoring of gastric
      intramucosal pH.
AB  - A novel method for continuously monitoring gastric intramucosal PCO2 and pH was
      developed and tested. Gas was continuously circulated through a modified balloon
      tipped catheter connected to an external closed system fitted with an infrared
      CO2 sensor to monitor PCO2. Performance of the capnometric recirculating gas
      tonometry (CRGT) system was tested in vitro using an equilibration chamber and in
      vivo in six anesthetized dogs. Serial PCO2 measurements were made using CRGT and
      compared with intermittent PCO2 values obtained by conventional tonometry
      catheters. In the animal experiments, gastric intramucosal PCO2 and pH were
      determined before and after inducing hypoxia by decreasing the Flo2 to 0.08.
      After initial placement, PCO2 determined by the CRGT reached a near plateau
      within 45 min, and at that time point values were comparable to those obtained by
      conventional intermittent tonometry. Significant increases in gastric
      intramucosal PCO2 were detectable by CRGT within 5 min of inducing systemic
      hypoxia, and there was a concomitant significant decrease in intramucosal pH.
      Continuous monitoring of gastric intramucosal PCO2 and pH is feasible, has
      potential advantages over conventional methods, and can provide significant
      trending information over intervals as short as 5 min.

PMID- 8564120
TI  - Persistent wheeze in grain elevator workers should not be ignored.
AB  - We investigated the relationship between annual change in pulmonary function and
      changes in respiratory symptoms among male grain elevator workers who
      participated in a health surveillance program mandated by Labour Canada. The
      surveillance was conducted every 3 yr starting from the period 1978 to 1981. The
      1,211 workers who participated in the second (1981 to 1984) and fifth (1990 to
      1993) surveillance were included in the analysis and the mean duration of the
      follow-up was 8.6 yr. In the analysis we also included the pulmonary function
      measurements that were available for some subjects at the third and fourth
      surveillance. The subjects who reported persistent wheeze had the largest mean
      annual rate change in FEV1 (-44.4 ml/yr) and FVC (-55.3 ml/yr). When adjusted for
      age, height, weight change, smoking, baseline lung function, location of grain
      elevators, and duration of employment, the subjects with persistent wheeze had an
      annual rate change of -28.3 ml/yr (SE 10.5; p = 0.007) in FEV1 and -37.3 ml/yr
      (SE = 12.3; p = 0.003) in FVC in comparison to subjects without any respiratory
      symptoms. The subjects who reported new onset of wheeze had significantly greater
      annual rate changes only in FEV1 (-13.7 ml/yr; SE 6.0; p = 0.02) in comparison to
      asymptomatic subjects' symptoms. Persistent wheeze is an important predictor of
      decline in lung function among grain elevator workers and should not be ignored
      in surveillance programs or clinical evaluations.

PMID- 8564121
TI  - Occupational disease trends in black South African gold miners. An autopsy-based
      study.
AB  - The change in prevalence in silicosis and pulmonary tuberculosis in black South
      African gold miners dying from unnatural causes from 1975 to 1991 was studied.
      Data were analyzed for 16,454 black gold miners. Information on age at death,
      duration of service, year of autopsy examination, and the prevalence of silicosis
      and tuberculosis was collected. Analyses were done to assess secular trends in
      the prevalence of tuberculosis and silicosis, and to determine predictors of the
      diseases at death. The prevalence of tuberculosis increased from 0.9% in 1975 to
      3.9% in 1991. The prevalence of silicosis increased from 9.3% to 12.8%. The
      prevalence of both diseases increased with age and duration of service. Silicosis
      was the most significant predictor of tuberculosis (odds ratio [OR] = 1.78,
      confidence limits [CL] = 1.27 to 2.30). A significant trend for tuberculosis, for
      year of autopsy, remained after adjustment for the other variables in the model,
      such as age and duration of service (p = 0.0046). In view of current labor
      stabilization in the South African mines, one can expect further increases in the
      prevalence of tuberculosis and silicosis. Lowering of dust levels in the mines is
      urgently required to prevent the increase of disease burden.

PMID- 8564122
TI  - Mineral fiber content of lungs in patients with mesothelioma seeking compensation
      in Quebec.
AB  - Asbestos fibers (AF) and ferruginous bodies (FB) in lung parenchyma from 50
      workers seeking compensation from the Workers' Compensation Board of Quebec for
      pleural or peritoneal mesothelioma were analyzed using transmission electron
      microscopy (TEM) equipped with energy-dispersive spectrometer (EDS) and phase
      contrast microscopy (PCM). These workers had been occupationally exposed in
      mining and milling activities (12 were from Asbestos Township and 11 from
      Thetford Mines) and 27 were from other types of industry (asbestos factory,
      shipyard, etc.). For comparison, analyses of lung tissue at autopsy were done in
      a group of 49 subjects from a reference population. A 95% confidence interval
      upper limit of 540 AF < 5 microns/mg and a 95% confidence interval upper limit of
      161 AF > or = 5 microns/mg dried lung tissue were found for the reference
      population. Similarly, a concentration of FB of 142 FB/g constituted the upper
      limit of detectable FB in the lungs of the reference population. Forty-eight of
      the 50 workers with mesothelioma had either a ferruginous body or total asbestos
      fiber count greater than the 95% confidence interval for the reference
      population; the remaining two had amosite and/or crocidolite concentrations
      greater than the 95% confidence interval for the reference population. The fiber
      types were different in the three groups, with the lungs of workers from Thetford
      Mines containing only chrysotile and tremolite, those from Asbestos Township
      containing chrysotile, tremolite, amosite, and crocidolite, and those in other
      industries containing largely amosite and crocidolite. We conclude that in this
      population of workers seeking compensation for mesothelioma, fiber analysis
      confirmed occupational asbestos exposure in every case. The fiber types
      responsible for the tumors are probably different in the three different groups.

PMID- 8564123
TI  - Socioeconomic status and lung function among primary school children in Canada.
AB  - We examined the relationship of lung function level to socioeconomic status (SES)
      using a cross-sectional design among 989 primary school children selected from 18
      Montreal schools and studied between April 1990 and November 1992. Information on
      each child's health, demographics, home exposure to tobacco smoke, pets, and
      cooking and heating fuel used in the child's home was collected by questionnaire.
      Spirometry was performed at school. Parental occupation was used to establish
      SES. After adjusting for personal, familial, and environmental factors, in boys
      but not in girls, FEV1 and FVC were progressively larger in higher categories of
      SES (p < 0.001 for linear trend). After taking into account the effect of
      multiple comparisons and adjusting for personal, familial, and environmental
      factors, boys from families in the lowest category of SES were found to have an
      FEV1 lower by 8.2% (95% CI, -13.8 to -2.1) and an FVC lower by 8.1% (95% CI, 
      13.4 to -2.6) when compared with the most advantaged. These results provide
      evidence that socioeconomic status, independent of common indoor exposures, is a
      risk factor for lower FEV1 and FVC among boys.

PMID- 8564124
TI  - Alveolar destruction in guinea pigs chronically exposed to diesel engine exhaust.
      A light- and electron-microscopic morphometry study.
AB  - Guinea pigs were exposed 16 h a day, 6 d a week, for 6, 12, 18, or 24 mo to
      filtered air or diesel-exhaust at low (NO2 = 0.22 +/- 0.03 ppm; SO2 = 0.60 +/-
      0.19 ppm; particles = 0.21 +/- 0.07 mg/m3), medium (NO2 = 1.07 +/- 0.09; SO2 =
      2.83 +/- 0.73; particles = 1.14 +/- 0.26) or high (NO2 = 2.88 +/- 0.29; SO2 =
      6.49 +/- 1.75; particles = 2.94 +/- 0.69) concentrations, or at a medium
      concentration without particles (NO2 = 1.01 +/- 0.09; SO2 = 2.66 +/- 0.64;
      particles = 0.01 +/- 0.01). We quantitated the holes in the alveolar wall and
      alveolar size by using scanning electron microscopy (SEM). After 12 mo of
      exposure, the ratio of the area of alveolar holes to that of the alveolar wall,
      and the number of holes per alveolus, rose as the concentration and duration of
      exposure increased. There were no differences in alveolar size between the study
      groups. Animals exposed to the medium concentration of diesel exhaust without
      particles showed less of an increase in the development of holes than animals
      exposed to the same concentration of diesel exhaust with particles. These
      findings suggest that diesel exhaust causes alveolar destruction (alveolar holes)
      without an enlargement in alveolar size in a concentration- and duration
      dependent manner. Particulate matter in diesel exhaust may play some role in the
      development of these lesions.

PMID- 8564125
TI  - Early detection of lung involvement in lysinuric protein intolerance: role of
      high-resolution computed tomography and radioisotopic methods.
AB  - Pulmonary disease of unknown etiology is a potentially fatal complication in
      patients with lysinuric protein intolerance (LPI), an autosomal recessive
      disorder caused by the defective transport of cationic amino acids. Lung
      involvement was investigated in nine Italian LPI patients through pulmonary
      function tests and lung imaging studies consisting of conventional chest
      radiography, high-resolution computed tomography (HRCT), and perfusion and
      ventilation scintigraphy. One 10-yr-old patient died of severe respiratory
      insufficiency from alveolar proteinosis. All of the remaining patients were
      asymptomatic at the time of the study, although HRCT scans revealed signs of lung
      involvement defined by the presence of acinar nodules, inter- and/or intralobular
      thickening of the interstitial septa, and subpleural cysts in five of the
      patients. Radioisotope studies showed an uneven distribution of perfusion and
      ventilation, and confirmed the presence of segmental and/or diffuse pulmonary
      functional defects. No abnormalities of pulmonary function were evident, and
      answers to a questionnaire excluded primary coexisting lung disease. In patients
      with LPI, including those without clinical and functional impairment, HRCT and
      radioisotopic studies appear to be the most sensitive methods for the early
      diagnosis of lung disease and correct assessment of its progression.

PMID- 8564126
TI  - A computer program using BALF-analysis results as a diagnostic tool in
      interstitial lung diseases.
AB  - Recently, we showed that it is possible to distinguish between three common
      interstitial lung diseases (ILD) with similarities in clinical presentation by
      using a number of selected variables derived from bronchoalveolar lavage fluid
      (BALF) analysis. The aim of this study was to develop a more general discriminant
      model, based on polychotomous logistic regression analysis. The 277 patients
      involved in the study belonged to diagnostic groups with sarcoidosis (n = 193),
      extrinsic allergic alveolitis (EAA; n = 39), and idiopathic pulmonary fibrosis
      (IPF; n = 45). The diagnosis had been established independently of the BALF
      analysis results. The variables used to discriminate among these patient groups
      were the yield of recovered BALF, total cell count, and percentages of alveolar
      macrophages, lymphocytes, neutrophils, and eosinophils. In order to test the
      predictive power of the logistic model, we used 128 patients having sarcoidosis
      (n = 91), EAA (n = 5), or IPF (n = 32) from another hospital. In this test set
      the agreement of predicted with actual diagnostic-group membership was the same
      as in the learning set in which the logistic model was fitted: 94.5% of the cases
      were correctly classified. A validated computer program based on the
      polychotomous logistic regression model can be used to predict the diagnosis for
      an arbitrary patient with information provided by BALF analysis, and is thought
      to be of diagnostic value in patients suspected of having ILD.

PMID- 8564127
TI  - Glutathione depletion in epithelial lining fluid of lung allograft patients.
AB  - The lower respiratory tract is protected against reactive oxygen species (ROS) by
      a complex antioxidant system. In the epithelial lining fluid (ELF), glutathione
      (L-alpha-glutamyl-L-cysteinylglycine, GSH) is essential for adequate protection
      of pneumocytes from potential toxicity mediated by extracellular hydrogen
      peroxide (H2O2). We assessed the concentration of total GSH in bronchoalveolar
      lavage fluid (BALF) in lung allograft patients in the absence and presence of
      acute rejection. Bronchoalveolar lavage (BAL) and biopsies were performed
      concurrently on 36 occasions in 17 patients who had undergone lung
      transplantation. BALF samples were divided into two groups on the basis of
      presence or absence of acute lung rejection on transbronchial biopsy. Seven BALF
      samples were obtained from control subjects for comparison. The BALF data
      demonstrated significantly lymphocyte recruitment and evidence of lung injury
      during acute rejection episodes. Transplant allografts without rejection showed
      significant depletion of total GSH in the ELF as compared with that of normal
      volunteers (94.0 +/- 9.7 microM versus 302.6 +/- 40.8 microM, p < 0.01).
      Transplant allografts with acute rejection had a slightly higher GSH
      concentration in their ELF (179.8 +/- 34.7), but this was still lower than
      control values. The deficiency of total GSH in the alveolar fluid may predispose
      lung allografts to extracellular H2O2-mediated toxicity.

PMID- 8564128
TI  - The effect of inhaled nitric oxide in pediatric asthma.
AB  - Nitric oxide (NO) appears to play an important role in regulating several
      biologic functions in the lung, including modulation of pulmonary arterial and
      bronchial smooth muscle tone. Recent studies have shown that relatively high
      concentrations of inhaled NO reduce the bronchoconstrictor effect of methacholine
      in animal models. This raises the possibility that NO inhalation might have
      therapeutic potential as an alternative bronchodilator. Although investigation of
      this potential in adults with airway reactivity or bronchial asthma has been
      reported, data are lacking on the role of NO in the pediatric asthma population.
      We therefore performed spirometry on 12 children with asthma (mean age 11.1 yrs)
      at baseline (B), immediately after inhaling 40 ppm NO (NO-1), 10 min after
      inhaling NO (NO-10), and after inhalation of a standard beta 2-agonist, albuterol
      (A). Baseline pulmonary functions (% predicted +/- SEM) were FVC of 103.2 +/-
      5.6, FEV1 of 82.2 +/- 3.3, FEF-max of 97.0 +/- 3.6, and FEF25-75% of 53.5 +/-
      3.3. There were no statistically significant differences between baseline and NO
      1 or NO-10 between any of the four pulmonary function parameters measured.
      Inhaled albuterol, however, resulted in significant improvement (% predicted +/-
      SEM) in FVC to 109.8 +/- 3.5, FEV1 to 99.7 +/- 2.9, FEFmax to 106.5 +/- 5.1, and
      FEF25-75% to 84.4 +/- 6.4 compared with the baseline and NO inhalation groups. We
      conclude that NO inhaled at 40 ppm has no apparent bronchodilatory effect in
      pediatric subjects with asthma and mild airways disease. The clinical application
      of this gas as a therapeutic modality under these conditions is questionable.

PMID- 8564129
TI  - Effect of rhDNase on airflow obstruction and mucociliary clearance in cystic
      fibrosis.
AB  - We tested the hypothesis that recombinant human deoxyribonuclease 1 (rhDNase)
      reduces airflow obstruction and improves mucociliary clearance in patients with
      cystic fibrosis (CF), and that improvements seen in FEV1 and FVC after rhDNase
      treatment are independent of chest physical therapy (CPT). CF patients inhaled
      placebo (10 patients) or 2.5 mg rhDNAse aerosol (10 patients) twice a day for six
      consecutive days. Compared with baseline, there were no statistically significant
      differences between the two study groups by Day 6 for indices of airflow
      obstruction obtained from gamma-camera images of the right lung following
      inhalation of 99mTc aerosol, or for mucociliary clearance or the rate of
      clearance of the radioaerosol, quantified over a 6-h period. By Day 6, FEV1 and
      FVC were significantly higher in the rhDNase-treated group than in the placebo
      group, increasing by an average of 9.4 +/- 3.5% and 12.7 +/- 2.6%, respectively,
      as compared with a decrease of 1.8 +/- 1.7% and an increase of 0.4 +/- 1.1%,
      respectively (p < 0.05). There was no significant change in the FEV1/FVC ratio on
      Day 6 (0.68 +/- 0.05) compared with baseline (0.70 +/- 0.05) in the rhDNase
      group. On Day 6, FEV1 and FVC decreased after CPT in both study groups, but the
      decreases were not significant. Our results indicate that aerosolized rhDNase
      improves FEV1 and FVC independent of CPT. We were unable to demonstrate that
      rhDNase reduces airflow obstruction or improves mucociliary clearance.

PMID- 8564130
TI  - Ventilatory responses to passive leg motion in children with congenital central
      hypoventilation syndrome.
AB  - During exercise, children with congenital central hypoventilation syndrome (CCHS)
      demonstrate coupling of VE to exercise load, despite the absence of a VE response
      to changes in FICO2. To assess the effect of movement on VE, we studied six CCHS
      patients and six matched controls during passive motion in a motor-driven
      ergocycle at pedaling frequencies (PF) of 6 to 60 rpm. VE, VO2, VCO2, VT, heart
      rate, respiratory rate, SPO2, and PETCO2 were measured. During steady-state
      conditions, VE was constant at PF of 0 to 30 rpm, but increased at PF > or = 40
      rpm in both controls and CCHS patients (p < 0.005). The increase in respiratory
      rate in CCHS patients was greater than in controls (p < 0.05) whereas VT
      increased similarly in both groups. At 60 rpm, VO2 increased in both groups, but
      VE/VO2 and VE/VCO2 increased in the CCHS patients and remained constant in the
      controls (P < 0.03; p < 0.04). From PF of 0 to 60, PETCO2 decreased from 47 +/- 7
      to 41 +/- 6 mm Hg in the CCHS patients (p < 0.001) but remained unchanged in the
      controls (38 +/- 3 mm Hg; p = NS). An analysis of on-transient responses at 60
      rpm revealed that VE increased immediately with the first breath after onset of
      motion in both groups, and that comparable differences in ventilatory patterns
      persisted in the two groups. We conclude that passive leg motion at PF > or = 40
      increases VE in both CCHS patients and controls. In controls, VE was tightly
      coupled to VO2 and VCO2. However, in CCHS patients, passive leg motion elicited
      normalization of PETCO2.

PMID- 8564131
TI  - Recovery of corticosteroid-induced changes in contractile properties and
      morphology of rat diaphragm.
AB  - Treatment with the fluorinated steroid triamcinolone (TR) induced type IIb fiber
      atrophy and the contractile profile of a slow muscle in rat diaphragm. In
      contrast, the nonfluorinated steroid prednisolone (PR) caused myogenic changes
      without fiber atrophy, and increased fatigability. The aim of the present study
      was to investigate the extent to which these changes were reversed 2 mo after
      discontinuation of treatment. Adult rats were randomly assigned to receive
      saline, PR 1.25 or 5 mg/kg, or TR 0.25, 0.5, or 1 mg/kg, intramuscularly daily
      during 4 wk. Administration of TR resulted in severe loss of body weight and dose
      dependent mortality. During recovery, body weight in the TR groups increased
      gradually, still remaining reduced compared with the other groups. Two months
      after discontinuation of treatment, diaphragm weight was increased in proportion
      to body weight. Twitch characteristics, maximal tetanic force, force-frequency
      curve, and fatigue resistance of isolated diaphragm bundles were similar in all
      groups. Histologic examination of the diaphragm revealed no gross abnormalities
      in the PR and TR groups. Mild but significant type IIb fiber atrophy was still
      present in the diaphragm and gastrocnemius muscle of all TR-treated animals. In
      conclusion, recovery of alterations in morphology of respiratory and peripheral
      skeletal muscles induced by administration of TR is prolonged.

PMID- 8564132
TI  - The effects of serotonin antagonists in an animal model of sleep-disordered
      breathing.
AB  - Recent studies have shown excitatory effects of serotonin on upper airway
      motoneurons. This excitatory effect is normally present and arises from cells in
      the caudal raphe nuclei. The firing of these serotonergic neurons is reduced
      during sleep. To determine the importance of serotonin in the maintenance of
      patient airways and normal respiration in waking in obstructive sleep apnea, we
      studied the effects of two serotonin antagonists on upper airway dilator muscle
      activity, diaphragm activity, Sao2, and upper airway cross-sectional area in an
      animal model of sleep-disordered breathing, the English bulldog. Systemic
      administration of both antagonists resulted in significant reductions in the peak
      amplitudes of upper airway muscle respiratory bursts (range, 39 to 62%
      suppression; p < 0.05). Lesser reductions in diaphragm activity were noted
      (range, 10 to 33% suppression; p < 0.05). Oxyhemoglobin saturations also fell (p
      < 0.05), coinciding with suppressions in upper airway muscle activity. With
      reductions in dilator muscle activity, upper airway cross-sectional areas, as
      measured with cine CT, showed significant inspiratory collapse. These results
      support the hypothesis that serotonin is important in the maintenance of patent
      upper airways in obstructive sleep apnea.

PMID- 8564133
TI  - Exhaustive exercise slows inspiratory muscle relaxation rate in chronic
      obstructive pulmonary disease.
AB  - The excessive load placed on inspiratory muscles when patients with COPD exercise
      could lead to fatigue and contribute to exercise limitation. Slowing of maximal
      relaxation rate (MRR) of skeletal muscle is an early index of the fatiguing
      process. We investigated whether inspiratory muscle MRR slows when patients with
      COPD walk to exhaustion. We studied nine well-trained and motivated patients with
      stable severe COPD (mean FEV1: 0.7 L, 28% predicted). Each subject performed
      sniff maneuvers before and after walking on a treadmill until they were forced to
      stop because of dyspnea. Esophageal (Pes), gastric, and transdiaphragmatic
      pressures were measured using balloon-tipped catheters. MRR was calculated as the
      percent Pes drop/10 ms. In the first minute after exercise there was a mean
      decrease of Pes MRR of 42% (range, 21 to 65%) (p < 0.01), which returned to
      baseline within 3 to 5 min. The fall in MRR indicates that the inspiratory
      muscles of patients with COPD walking to exhaustion are sufficiently heavily
      loaded to initiate the fatiguing process.

PMID- 8564134
TI  - Efficacy of auto-CPAP in the treatment of obstructive sleep apnea/hypopnea
      syndrome.
AB  - The auto-CPAP (Morphee Plus) is characterized by its ability to modify the
      positive-pressure level applied during the night for the presence or absence of
      sleep-induced respiratory disorders. The aim of the study was to compare the
      efficacy of this new mode of CPAP therapy with that of conventional constant-CPAP
      in the treatment of sleep apnea/hypopnea syndrome (SAHS). Sixteen patients with
      SAHS were randomly allocated to two groups that were paired for age,
      apnea/hypopnea index, and mean sleep latency. In the auto-CPAP group, the
      pressure level could change within fixed limits in both directions (+2 to -4 cm
      H2O) of the previously determined effective pressure level (Peff). In the
      constant-CPAP group, patients used the same apparatus (Morphee Plus) in a
      constant mode at Peff level. At the beginning of the study, the Peff level was
      determined during a polysomnographic recording. Day-time vigilance was measured
      subjectively by a standardized questionnaire and objectively by the maintenance
      of wakefulness test (MWT); Trailmaking tests (TMT) were used to evaluate
      cognitive functions. After 3 wk of home CPAP therapy, a control sleep study was
      done with the CPAP machine used in the protocol, and daytime vigilance and
      cognitive function tests were obtained. Baseline sleep and nocturnal breathing
      disorders characteristics did not differ between the two groups, and daytime
      vigilance and cognitive function abnormalities were similarily altered. In both
      groups, the apnea/hypopnea index was within normal range at the final CPAP sleep
      study. In the auto-CPAP group, 49.3 +/- 14.9% (mean +/- SD) of home treatment
      time was spent at a pressure < or = Peff. Home amount of use estimated by the
      number of sleeping hours with a positive pressure applied was 6.5 +/- 1.0 h in
      the auto-CPAP group and 5.1 +/- 1.1 h in the constant-CPAP group (p = 0.02).
      During the control CPAP sleep study, the positive pressure level was
      significantly lower during Stage III-IV than during the other sleep stages (p =
      0.004). The improvement in the MWT and the TMT observed with CPAP therapy was
      identical in both groups. We conclude that (1) the amount of use during CPAP
      treatment is higher with auto-CPAP than with constant-CPAP, and (2) Morphee+auto
      CPAP is an efficient as conventional CPAP in correcting nocturnal breathing
      disorders, daytime sleepiness, and cognitive impairment in SAHS.

PMID- 8564136
TI  - Reference values for pulmonary function tests of Japanese-American men aged 71 to
      90 years.
AB  - Pulmonary function was assessed by spirometry in 3,076 elderly Japanese-American
      men of the Honolulu Heart Program (HHP) cohort. The assessment was done with a
      stringent quality assurance program that adhered to American Thoracic Society
      (ATS) recommendations for spirometry. Less than 6% of the participants were
      unable to perform three acceptable spirometry maneuvers. A "healthy" subgroup of
      528 men between the ages of 71 and 90 yr was identified by excluding almost all
      smokers and subjects with lung disease and other factors negatively influencing
      FEV1. Reference equations and normal ranges for FEV1, FVC, and the FEV1/FVC ratio
      were derived from the healthy group. Use of prediction equations from the
      Cardiovascular Health Study (CHS) of elderly European-American men consistently
      overpredicted FVC by 0.3 to 0.4 L and FEV1 by 0.15 L. Men in the HHP were on
      average 11 cm shorter than those in the CHS. Use of a prediction equation derived
      from the HHP cohort when the men in the cohort were on average 22.6 yr younger
      consistently overpredicted FEV1 by 0.2 to 0.3 L. These results underscore the
      importance of using prediction equations appropriate to the ethnicity, age, and
      height characteristics of the subjects being studied.

PMID- 8564135
TI  - Increased release of interleukin-1 beta, interleukin-6, and tumor necrosis factor
      alpha by bronchoalveolar cells lavaged from involved sites in pulmonary
      tuberculosis.
AB  - Mycobacterium tuberculosis and its components have been shown to stimulate
      mononuclear phagocytes in vitro to release interleukin-1 beta (IL-1 beta), tumor
      necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). Animal models of
      tuberculosis (TB) also demonstrate the presence of cytokines in granulomas. We
      hypothesized that bronchoalveolar lavage (BAL) cells from patients with pulmonary
      TB would have increased spontaneous release of IL-1 beta, IL-6, and TNF-alpha and
      would have a concomitant alveolitis. We performed BAL on 26 patients with active
      TB and on six normal volunteers. BAL fluid from radiographically involved and
      uninvolved sites was evaluated separately for cell types and the spontaneous
      release of cytokines. The alveolar inflammation in involved sites was
      characterized by an increase in lymphocytes (miliary TB, 38 +/- 10%; involved
      sites, 22 +/- 4%; uninvolved sites, 13 +/- 2%; normal, 5 +/- 2%) and neutrophils
      (involved sites, 21 +/- 7%; uninvolved sites, 3 +/- 2%). There was a significant
      increase in the spontaneous release of IL-1 beta (501 +/- 280 pg/ml), TNF-alpha
      (782 +/- 165 pg/ml), and IL-6 (473 +/- 157 pg/ml) from involved sites of TB
      patients that was 5- to 20-fold greater than uninvolved sites, normal controls,
      or miliary TB. Northern analysis revealed increased gene expression of IL-1 beta,
      TNF-alpha, and IL-6 from the involved sites from two patients with TB compared
      with two negative controls. We conclude that BAL cells, especially alveolar
      macrophages, are activated in the alveolar inflammation of active TB and
      spontaneously release increased quantities of IL-1 beta, IL-6, and TNF-alpha, and
      that these cytokines are likely to be involved in directing granuloma formation
      and control of M. tuberculosis infection.

PMID- 8564137
TI  - Angiotensin-converting enzyme inhibitor and danazol increase sensitivity of cough
      reflex in female guinea pigs.
AB  - To examine the mechanisms of an angiotensin-converting enzyme (ACE) inhibitor
      induced cough in perimenopausal and postmenopausal women, cough responses to
      aerosols of capsaicin and citric acid were examined in four groups of female
      guinea pigs treated orally with danazol (D) (an agent decreasing plasma estrogen
      levels), cilazapril (C) (an inhibitor of ACE), both danazol and cilazapril (C+D),
      or without either drug (control group) for 4 to 5 wk. Capsaicin caused dose
      dependent increases in the number of coughs in all four groups. C or D alone
      shifted dose-response curves to capsaicin (from 10(-7) M to 10(-3) M) to lower
      concentrations compared with the control, and C+D further shifted them. Likewise,
      the number of coughs induced by citric acid (3 x 10(-1) M; 2 min) was highest in
      animals treated with C+D and significantly higher in animals treated with C or D
      than in the control group. Aerosols of a selective substance P (SP) receptor
      antagonist FK 888 (10(-5) M; 2 min) inhibited capsaicin-induced cough in all four
      groups, and dose-response curves to capsaicin did not differ significantly at any
      concentrations among the four groups in the presence of FK 888 (p > 0.10). D
      decreased cyclic AMP levels in the trachea, irrespective of the combination of C.
      A beta 2-adrenoceptor agonist, procaterol, which is thought to inhibit SP release
      by elevation of cyclic AMP in sensory nerves, dose-dependently inhibited the
      number of coughs induced by capsaicin (10(-3) M) in animals treated with D. The
      present study suggests that SP is a common mechanism mediating increases in the
      sensitivity of cough reflex induced by both ACE inhibition and a decrease in
      plasma estrogen levels, and the additive effects of the two events may explain
      the high incidence of cough during ACE inhibitor therapy in perimenopausal and
      postmenopausal women.

PMID- 8564138
TI  - Exogenous surfactants in a piglet model of acute respiratory distress syndrome.
AB  - Evidence for surfactant dysfunction in acute respiratory distress syndrome (ARDS)
      suggests a role for exogenous surfactant which contains apoprotein for resistance
      to protein inhibition. We compared the effects of KL-4-Surfactant, an artificial
      preparation containing a synthetic 21 amino acid peptide with SP-B-like activity,
      with Exosurf, an artificial protein-free surfactant, and Survanta, a bovine
      protein-containing surfactant, in a saline lung lavage model of ARDS in neonatal
      piglets. Two sequential series of lung lavages were performed to lower PaO2 < 100
      mm Hg, each followed by administration of surfactant or air and a 90-min
      observation period. Progressive lung injury was demonstrated by deterioration in
      pulmonary function, increasing bronchoalveolar lavage protein, and changes in
      histopathology. All surfactants improved oxygenation, although oxygenation was
      generally better with Survanta and KL-4-Surfactant. Further, Survanta and KL-4
      Surfactant groups showed improvement in ventilation, with decreases in PaCO2 and
      increases in FRC. Only KL-4-Surfactant demonstrated greater pressure-volume
      characteristics and lower bronchoalveolar protein than those of Controls. We
      conclude that the physiologic effects of KL-4-Surfactant are more like Survanta
      in this model. We speculate that KL-4-Surfactant may improve pulmonary function,
      reduce alveolar protein leak, and thus be efficacious in the treatment of ARDS.

PMID- 8564139
TI  - Nasal contribution to exhaled nitric oxide at rest and during breathholding in
      humans.
AB  - We characterized the nasal contribution to exhaled nitric oxide (NO) at rest and
      during breathholding in humans. Exhaled NO was greater during nose breathing (141
      +/- 17 nl/min/M2, mean +/- SEM) compared with mouth breathing (68 +/- 6
      nl/min/M2, n = 8, p < 0.001). After voluntary closure of the soft palate (VCSP)
      to eliminate nasal NO, exhaled NO from the mouth decreased further (30 +/- 4
      nl/min/M2, p < 0.001). Release of NO into nasal passages during VCSP (217 +/- 19
      nl/min/M2) was greater than exhaled NO during nasal breathing (141 +/- 17
      nl/min/m2, p < 0.001), suggesting that nasal NO is taken up by the respiratory
      tract. During mouth breathing or nose breathing, NO concentrations sampled with a
      bronchoscope were higher in the nasopharynx than at the epiglottis or in the
      trachea in five subjects. Increased peak exhaled NO after a breathhold (33 +/- 7
      ppb) was reduced (10 +/- 4 ppb, p < 0.001) after balloon occlusion of the
      nasopharynx. NO concentration during breathholding increased to a greater extent
      in the nasopharynx than in the pharynx or trachea. We conclude that the majority
      of exhaled NO at rest and during a breathhold originates in the nasopharynx.

PMID- 8564140
TI  - Independent origin of mono-rifampin-resistant Mycobacterium tuberculosis in
      patients with AIDS.
AB  - Historically, infections caused by Mycobacterium tuberculosis have been treated
      simultaneously with isoniazid and rifampin. As a consequence of this combined
      therapy, strains resistant only to rifampin were rarely recovered. However,
      recently there has been an increasing number of reports describing HIV-positive
      patients infected with mono-rifampin-resistant M. tuberculosis strains. Organisms
      cultured from seven patients (including six with AIDS) with infections caused by
      mono-rifampin-resistant M. tuberculosis, and seen at one New York City hospital,
      were analyzed by molecular techniques to test the hypothesis that dissemination
      of a single clone had occurred. IS6110 DNA fingerprinting and automated DNA
      sequencing of a region of the RNA polymerase beta subunit structural gene (rpoB)
      containing mutations that confer rifampin resistance showed that all organisms
      independently acquired the mono-rifampin-resistant phenotype. Molecular analysis
      of mono-rifampin-resistant organisms cultured from 13 additional patients in New
      York City confirmed independent strain origin. The data rule out the possibility
      of person-to-person strain transmission among these patients, and they suggest
      that host factors such as poor compliance with antituberculosis medications or
      decreased absorption of rifampin have been a driving force in the origin of these
      strains.

PMID- 8564141
TI  - Permeability of human isolated airways increases after hydrogen peroxide and poly
      L-arginine.
AB  - In asthma, the airway epithelium may be damaged by oxidants and cationic proteins
      produced by eosinophils. The degree of epithelial damage correlates with the
      level of bronchial hyperreactivity. An increase in airway permeability to
      bronchoactive agonists may be one of the factors responsible for airway
      hyperresponsiveness in asthma. We investigated the effects of the oxidant
      hydrogen peroxide and the major basic protein (MPB) analogue poly-L-arginine on
      the permeability and morphology of nonasthmatic human peripheral airways. In
      addition, we examined whether airway permeability depends on airway size. Human
      airway tubes (generation 7 to 12) mounted in an organ bath were luminally
      perfused with Krebs-Henseleit buffer containing the hydrophilic tracer 111In
      diethyletriamine pentaacetic acid (111In-DTPA) or the lipophilic tracer 14C
      antipyrine (14C-AP). Permeability of the airways was calculated from the fluxes
      of the tracer molecules across the airway wall. After experiments, light- and
      electromicroscopic examination of the airway epithelium was performed. Baseline
      permeability to 14C-AP was five times greater than to 111In-DTPA. Luminal
      exposure of the airways to 100 mmol/L H2O2 produced a significant, sixfold
      increase in permeability to 111In-DTPA but not to 14C-AP, indicating the opening
      of paracellular pathways. The H2O2-induced increase in permeability was partly
      reversible. Luminal exposure to polyarginine for 3 h and 16 h produced a
      significant 4.5- and 7-fold increase in permeability to 111In-DTPA, respectively.
      Histologic examination of epithelium exposed to H2O2 of poly-L-arginine showed
      focal loss of superficial cells with preservation of basal cells. Baseline airway
      permeability increased with decreasing airway size (rs = -0.75, p < 0.01). These
      results suggest that epithelial damage due to eosinophil products may increase
      airway permeability, and that this may at least partly explain the increased
      responsiveness to inhaled stimuli in asthma.

PMID- 8564142
TI  - Expression of nitric oxide synthase in the human nasal mucosa.
AB  - The nasal mucosa plays an important role in defense of the lung against harmful
      agents. It has been suggested that this is partly mediated by the production of
      nitric oxide (NO). We have investigated the localization of the messenger
      ribonucleic acids (MRNAs) for human endothelial NO synthase (Type III NOS) and
      inducible NO synthase (Type II NOS) and the immunoreactivities of these enzymes
      in human nasal mucosa by immunohistochemistry, in situ hybridization, and reduced
      nicotinamide adenine diphosphate (NADPH) diaphorase histochemistry. Inferior
      nasal turbinates were obtained from 27 patients at the time of surgery for local
      disease. Strong immunostaining for Type III NOS was localized to vascular
      endothelium, surface epithelium, and submucosal glands in all subjects. Moderate
      immunostaining for Type II NOS was seen in surface epithelium; glandular,
      inflammatory, and vascular endothelial cells; and smooth-muscle cells in the
      specimens from patients with chronic rhinitis only. In situ hybridization showed
      expression of the mRNA for Type III NOS in similar sites to those shown by
      immunohistochemistry, whereas the mRNA for Type II NOS was predominantly
      localized to inflammatory cells. The sites of NOS expression were further
      confirmed by NADPH histochemical staining. These findings demonstrate the
      cellular expression of NOS in the human nasal mucosa and suggest a possible role
      for Types II and III NO synthase in the regulation of blood flow, nasal
      secretion, and ciliary movement in health and disease.

PMID- 8564143
TI  - Polymorphism of angiotensin-converting enzyme gene in sarcoidosis.
AB  - Sarcoidosis is the disease in which increased levels of serum Angiotensin
      converting enzyme (sACE) are most often detected. It has recently been shown that
      the deletion (D) or the insertion (I) of a 250bp-DNA fragment in the ACE gene
      accounts for three main ACE genotypes (i.e., II, ID, and DD) and for 47% of total
      phenotypic variance in sACE level. The aim of our work was to investigate whether
      or not patients with sarcoidosis have an increased incidence of those ACE
      genotypes coding for highest sACE levels and to investigate whether or not sACE
      level in sarcoidosis is related to ACE genotypes. We studied 61 unrelated
      patients with sarcoidosis (test group) and 80 unrelated healthy control subjects
      (control group). The ACE I and D alleles were detected with polymerase chain
      reaction on genomic DNA. In the control group we found an ACE genotype
      distribution that agreed with the Hardy-Weinberg proportion. The ACE genotype
      distribution was not significantly different in the test group. There was no
      correlation between ACE genotype and roentgenologic stage of sarcoidosis.
      Plotting the sACE level in the control group against ACE genotype, we found a
      trend of increasing mean sACE value according to the order II < ID < DD. The same
      trend for ACE genotype was found in the test group, in which it also paralleled
      the trend of sACE values plotted against roentgenologic stage, according to the
      order Stage I < Stage II < Stage III. We conclude that in sarcoidosis the ACE
      genotype distribution is not altered. The trends for increasing sACE values in
      sarcoidosis according to both ACE genotype and roentgenologic stage would suggest
      that both mechanisms play a role in determining sACE level.

PMID- 8564144
TI  - Reliability of quantitative cultures of protected specimen brush after freezing.
AB  - Protected specimen brush (PSB) is considered to be one of the standard methods
      for diagnosing mechanical ventilator-acquired pneumonia at a threshold value > or
      = 10(3) cfu/ml. Nevertheless, this procedure requires immediate cultures which
      are not always possible 24 h per day. We therefore wanted to appreciate the
      diagnostic value of delayed quantitative cultures after specimen freezing. PSB
      was performed by fiberoptic bronchoscopy on 43 mechanically ventilated patients
      with suspicion of nosocomial bronchopneumonia. After PSB procedure, two aliquots
      of 0.5 ml were prepared. One aliquot was plated immediately on different culture
      media (Group 1). A second aliquot was frozen at -80 degrees C for 24 h, then
      plated on the same culture media as Group 1 (Group 2). All samples were incubated
      for 48 h. The diagnostic value threshold of PSB was 10(3) cfu/ml. A total of 47
      samples were performed on 43 patients. In Group 1, cultures from PSB were
      positive in 26 samples and revealed 41 species yielding > or = 10(3) cfu/ml. In
      Group 2, PSB cultures were positive in 24 samples and revealed 36 species
      yielding > or = 10(3) cfu/ml. Despite a mean decrease in bacterial count of 1.00
      +/- 1.44 log 10 (p < 0.001), most important for Streptococcus pneumoniae and
      Escherichia coli (respectively 3.22 +/- 2.21 log10 and 2.41 +/- 0.52 log 10),
      sensitivity and specificity of quantitative cultures after specimen freezing,
      compared with immediate cultures, were 88% and 100% respectively. We concluded
      that specimens from PSB could be frozen at -80 degrees C with good reliability
      except for S. pneumoniae and E. coli, enabling PSB procedure to be performed
      around the clock.

PMID- 8564145
TI  - Cystic fibrosis 3849+10kb C > T mutation associated with severe pulmonary disease
      and male fertility.
AB  - A 40-yr-old Hispanic man presented to NJCIRM with end-stage lung disease.
      Evaluation of this patient 10 yr earlier noted bronchiectasis, normal sweat
      electrolytes, pancreatic sufficiency, delayed progression of pulmonary disease,
      and a sperm biopsy consistent with fertility. At the time of admission
      bronchiectasis was extensive. DNA testing demonstrated homozygosity for the
      3849+10kb C > T cystic fibrosis (CF) allele. This is the first description of
      homozygous expression of this allele in a male patient. Confirmation of fertility
      was established by demonstrating that his children were carriers of this allele.
      This patient emphasizes the importance of DNA testing for atypical CF alleles in
      patients with bronchiectasis of undetermined cause even in the presence of
      fertility, normal pancreatic function, and normal sweat electrolytes.

PMID- 8564146
TI  - Cigarette smoking and health. American Thoracic Society.
AB  - Cigarette smoking remains the primary cause of preventable death and morbidity in
      the United States. Smoking causes lung cancer, COPD, and CHD and contributes
      significantly to mortality from other conditions such as stroke. Maternal smoking
      during pregnancy causes low birthweight and perinatal mortality, and it may have
      lasting impact on the child's physical and cognitive growth. Passive exposure to
      ETS causes lung cancer and poses particular danger to the respiratory health of
      young children. Smoking cessation strategies are important, but the should be
      supplemented by community and policy-level interventions. Workplace or community
      smoking bans, statewide taxes on tobacco, and antismoking media campaigns may be
      effective adjuncts to individual cessation strategies. These strategies may be an
      even more important disincentive to smoking initiation. The expanding horizon of
      health consequences of smoking and its costs to American society should again
      challenge public health agencies to develop and implement effective strategies to
      prevent smoking acquisition by young people. These health effects should also
      motivate health professionals in other countries where smoking prevalence is
      increasing, rather than decreasing, to initiate more effective efforts to reverse
      this trend and minimize the excess morbidity and death that accompany this
      dangerous habit.

PMID- 8564147
TI  - Standards and indications for cardiopulmonary sleep studies in children. American
      Thoracic Society.

PMID- 8564148
TI  - Oral and inhaled corticosteroids reduce bone formation as shown by plasma
      osteocalcin levels.

PMID- 8564149
TI  - Development of a non-linear finite element modelling of the below-knee prosthetic
      socket interface.
AB  - A non-linear finite element model has been established to predict the pressure
      and shear stress distribution at the limb-socket interface in below-knee amputees
      with consideration of the skin-liner interface friction and slip. In this model,
      the limb tissue and socket liner were respectively meshed into 954 and 450 three
      dimensional eight-node isoparametric brick elements, based on measurements of an
      individual's amputated limb surface; the bone was meshed into three-dimensional
      six-node triangular prism elements, based on radiographic measurements of the
      individual's residual limb. The socket shell was assumed to be a rigid boundary.
      An important feature of this model is the use of 450 interface elements (ABAQUS
      INTER4) which mimic the interface friction condition. The results indicate that a
      maximum pressure of 226 kPa, shear stress of 53 kPa and less than 4 mm slip exist
      at the skin-liner interface when the full body weight of 800 N is applied to the
      limb. The results also show that the coefficient of friction is a very sensitive
      parameter in determining the interface pressures, shear stresses and slip. With
      the growth of coefficient of friction, the shear stresses will increase, while
      the pressure and slip will decrease.

PMID- 8564150
TI  - Measurement of tooth displacements and mouthpiece forces during brass instrument
      playing.
AB  - In order to assess the actual load on front teeth and tooth supportive tissue
      during brass instrument playing, a measuring system was developed permitting
      simultaneous recordings of mouthpiece forces and incisor deflections. By the
      application of strain gauges, the mouthpiece itself was converted into an extra
      oral force transducer, whilst an intra-oral metal appliance similar to a
      removable partial denture served as the base for strain gauge transducers sensing
      incisor displacements. The measurements only slightly affected the handling of
      the instruments under examination (trumpet, french horn, tenor horn, and tuba)
      and yielded the following average results for three to five players per
      instrument: peak force values were in the range of 29 N (tuba) to 50 N (trumpet),
      and the respective peak displacements were 43 microns and 100 microns.

PMID- 8564151
TI  - The time-variable photoplethysmographic signal; dependence of the heart
      synchronous signal on wavelength and sample volume.
AB  - The photoplethysmorgraphic signal (PPG) from forearm skin and the ECG were
      recorded simultaneously from healthy subjects. The optical signal was derived
      with a fibre-optic probe which consisted of 61 fibre pairs. The peak-to-peak
      averaged a.c.-signal was calculated. The dependency of this signal and the signal
      to-noise ratio (SNR) on the light wavelength and on sample volume was studied.
      The light intensities used at 560 nm were 0.015 and 0.029 mWmm-2 and at 940 nm we
      used 0.029, 1.37 and 2.77 mWmm-2. A theoretical model for calculation of the
      sample volumes was also developed. The amplitude and SNR of the a.c.-signal at
      560 nm is larger than at 940 nm at the same intensity (0.029 mWmm-2). At 940 nm
      using 1.37 and 2.77 mWmm-2 the a.c.-signal increased with the number of fibre
      pairs (volume) while the SNR was little affected. At 560 nm it is suggested that
      the major contribution to the a.c.-signal is pulsations in the ascending
      arterioles and at 940 nm from pulsations in the larger vessels deeper in the
      tissue volume under study.

PMID- 8564152
TI  - A neural network confirms that physical exercise reverses EEG changes in
      depressed rats.
AB  - The use of an artificial neural network (ANN) system to differentiate the EEG
      power density spectra in depressed from normal rats was tried. The beneficial
      effects of chronic physical exercise in reducing the effects of stress and
      therefore depression was also to be tested in animals by the same method. In this
      study, rats were divided into 4 groups, subjected to (i) chronic stress (D
      group); (ii) chronic exercise by treadmill running (EO group); (iii) exercise
      with stress (ES group) and (iv) handling (C group). The prefrontal cortical EEG,
      EMG and EOG were recorded simultaneously on paper and the digitized EEG signals
      were also stored in the hard-disk of a PC-AT through an ADC. After filtering the
      digitized signals, the EEG power spectra were calculated by an FFT routine. Three
      successive 4 s artefact-free epochs were averaged. The REM and NREM sleep periods
      as well as the awake period signals were analyzed separately. The FFT values from
      each of the 3 states, in the 4 groups of animals were tested by an ANN with 30
      first layer neurons and a 2nd layer of a majority-vote-taker. The ANN could
      distinguish the depressed from the normal rats' EEG very well in REM (99%) sleep,
      NREM (95%) sleep and awake (81%) states. In most of the cases it identified the
      exercised rats' EEG as normal.

PMID- 8564153
TI  - Localization of knee joint cartilage pathology by multichannel vibroarthrography.
AB  - This paper proposes non-invasive techniques to localize sound or
      vibroarthrographic (VAG) signal sources in human knee joints. VAG signals from
      normal subjects, patients who subsequently underwent arthroscopy, and cadavers
      with arthroscopically-created lesions, obtained by stimulation with a finger tap
      over the mid-patella and swinging movement of the leg, were analyzed for time
      delays using cross-correlation functions for source localization. Correct results
      were obtained for 13 of the 14 subjects tested by finger stimulation, and for 11
      of the 12 subjects whose VAG signals during swinging movement were analyzed. The
      techniques could be valuable in the diagnosis and treatment of knee pathology
      before and after joint surgery or drug therapy.

PMID- 8564154
TI  - Spectro-temporal studies of Xe-Cl excimer laser-induced arterial wall
      fluorescence.
AB  - We report on spectro-temporal fluorescence studies of cadaver femoral arterial
      walls at different stages in the progression of atherosclerosis. After excitation
      with a Xe-Cl excimer pulse, the time course of the fluorescence spectrum was
      recorded over time, and time-resolved multispectral analysis was performed. Then,
      under the assumption of linearity, we derived a linear spectro-temporal kernel (a
      weighting function) which describes the temporal behavior of the fluorescence
      process independently of the pulse width of the photoexcitation. The data
      analysis revealed both static and dynamic fluorescence characteristics which
      exhibited a good correlation with histological findings.

PMID- 8564155
TI  - Realistic three-dimensional left ventricular ejection determined from
      computational fluid dynamics.
AB  - A realistic model of the left ventricle of the human heart was constructed using
      a cast from a dog heart which was in diastole. A coordinate measuring machine was
      used to measure and digitize the coordinates of the left ventricle. From the
      complex measured left ventricle shape values, a three-dimensional finite volume
      representation was constructed using a simulation package. The left ventricular
      walls moved towards the centre of the aortic outlet in order to study the effects
      of time-varying left ventricular ejection. The left ventricular wall motion was
      assumed to follow the blood flow and the wall grid was reformed 25 times during
      the calculation. The 25.8 cm3 ventricular volume was reduced by 75% in 0.25 s.
      Centreline and cross-sectional velocity vectors greatly increased in magnitude at
      the aortic outlet, and most of the pressure occurred in the top 15% of the heart.
      The computational method should make it possible to compare simulation results
      with important measurement techniques such as ultrasound and magnetic resonance
      imaging, and this should allow a finer detail of flow understanding than is
      presently available using either a modelling or imaging method alone.

PMID- 8564156
TI  - Fluid-structure interaction problems in bio-fluid mechanics: a numerical study of
      the motion of an isolated particle freely suspended in channel flow.
AB  - In this paper a problem belonging to the moving boundary class is tackled with a
      2-D application of computational fluid dynamics techniques. The motion of an
      isolated rigid particle freely suspended in an incompressible Newtonian fluid in
      a narrow channel is studied numerically at a low Reynolds number, yet different
      from zero. The actual problem consists of two coupled problems: the motion of the
      viscous fluid and that of the rigid particle suspended and convected with the
      fluid. The full Navier-Stokes equations (i.e. both transient and convective terms
      are included) are solved in the fluid domain by means of the finite element
      method, while the motion of the particle is determined on the basis of a rigid
      act of motion. Results from simulations corresponding to differential initial
      positions of the particle are shown in this paper: they allow one to study the
      rotational motions of the particle as well as its displacements. The goal of the
      paper is to analyse the lateral displacement behaviour of the particle, already
      observed in experimental studies in microcirculation. In particular, lateral
      migrations are supposed to be due to inertial forces acting in the fluid around
      the moving particle combined with the proximity of the resting wall (wall
      effect). Preliminary results are in fairly good agreement with those available in
      the literature.

PMID- 8564158
TI  - Three-dimensional simulation of epicardial potentials using a microcomputer-based
      heart-torso model.
AB  - Previous cardiac simulation studies have focused on simulating the activation
      isochrones and subsequently the body surface potentials. Epicardial potentials,
      which are important for clinical applications as well as for electrocardiography
      inverse problem studies, however, have usually been neglected. This paper
      presents a procedure of simulating epicardial potentials using a microcomputer
      based heart-torso model with real geometry. The heart model developed earlier
      which was composed of more than 60,000 cell units was used in this study. To
      simulate the epicardial potentials, an epicardial surface model which enclosed
      the whole heart was constructed. The heart model, together with the epicardial
      surface model, are mounted in an inhomogeneous human torso model. Electric
      dipoles, which are proportional to the spatial gradient of the action potential,
      are generated in all cell units. These dipoles give rise to a potential
      distribution on the epicardial surface, which is calculated by means of the
      boundary element method. The simulated epicardial potential maps during a normal
      heart beat and in patients with left bundle branch block (LBBB) are in close
      agreement with those reported in the literature.

PMID- 8564157
TI  - The design and performance of an experimental external fixation device with load
      transducers.
AB  - It is becoming increasingly common that fracture healing is modelled in the
      laboratory with an osteotomy in the diaphysis of the ovine tibia. External
      fixation is often used to hold the bones in these models, presenting the problem
      that the loads on such devices are poorly understood. To help investigate this, a
      unilateral device has been developed which is capable of measuring the two
      components of load considered to be the most important, that of axial compression
      and bending in the plane of the fixator. The device was found to be a rigid
      system and easy to apply, with the in-vivo measurements being straightforward.
      The estimated limits of error of the compression transducer are +37.9 N and -21.4
      N and those of the bending transducer are +3.6 Nm and -4.2 Nm. Preliminary
      measurements showed the maximum load during normal walking to 345 N compression
      and 28 Nm in-plane bending.

PMID- 8564159
TI  - [A model contract for ambulatory nursing services].

PMID- 8564160
TI  - [Nursing insurance, second step. Home residents turn into customers].

PMID- 8564161
TI  - [Skin problems in old age. The largest human organ deserves more attention].

PMID- 8564162
TI  - [Nursing injustice].

PMID- 8564163
TI  - [Bonn stops nursing personnel rules for a year. The nurses' protest is not being
      heard].

PMID- 8564164
TI  - [Seniors in the nursing market: a study. The elderly know exactly what they
      want].

PMID- 8564165
TI  - [The quality seal protects seniors who need help. Assisted living is no longer a
      gamble].

PMID- 8564166
TI  - [The psychologically unusual child in school].

PMID- 8564167
TI  - [A short portrait: the Dresden Diakonic House after unification. "Education has
      deteriorated"].

PMID- 8564168
TI  - [Ethical problems in the nursing of brain-dead organ donors. We are functioning
      in spite of conflicting feelings].

PMID- 8564169
TI  - [Natural care in nursing. Possibilities and limits. Alternative nursing methods
      increase wellbeing].

PMID- 8564170
TI  - [Dying in the hospital. 3. Ways of handling dying and death in the hospital].

PMID- 8564171
TI  - [Fire prevention in the hospital. "Can you carry the fire extinguisher?"].

PMID- 8564172
TI  - [A new task: care counseling. Professional autonomy is legally established].

PMID- 8564173
TI  - [Technical surgical assistant (TOA) a thriving profession].

PMID- 8564174
TI  - [The historical development of a role figure. "Nurses are cheap, willing and
      good"].

PMID- 8564175
TI  - Curricular training in general surgery.

PMID- 8564176
TI  - General lessons from cutaneous lymphoma.

PMID- 8564177
TI  - Therapeutic options in diabetic renal disease and hypertension.
AB  - Diabetic renal disease must now be regarded as a condition that can be prevented
      in a proportion of cases. Improved glycaemic control in the early stages of type
      I disease, and blood pressure control at all stages is essential in all patients
      with diabetes.

PMID- 8564178
TI  - Abscess drainage techniques.
AB  - Percutaneous abscess drainage of infected and sterile collections within the body
      is a cost and clinically effective technique. The principles and pitfalls of the
      technique are outlined and an algorithm is included to aid patient management.

PMID- 8564179
TI  - Cryptococcal meningitis.
AB  - Fungal meningitis caused by the yeast Cryptococcus neoformans is most commonly
      seen in patients with defective T-lymphocyte function. This article focuses on
      the clinical presentation, diagnosis and management of patients with cryptococcal
      meningitis, in the setting of AIDS and other immunocompromised hosts, and in
      'normal' individuals.

PMID- 8564180
TI  - Fetal malformations diagnosed antenatally. 2: Ultrasound diagnosis of fetal
      structural anomalies.
AB  - Paediatricians should be consulted about the significance of abnormalities seen
      on antenatal ultrasound scans. Good teamwork and communication is necessary
      between the obstetrician, paediatrician and ultrasonographer to explain the
      significance of any abnormality to a pregnant woman. Follow-up is important both
      for the parents and for audit purposes.

PMID- 8564181
TI  - Examination questions in cardiology: 2.

PMID- 8564182
TI  - Investigation of haematuria.
AB  - Haematuria is a common symptom and sign that may be encountered in almost all
      medical specialties. The possibility that haematuria may signal an underlying
      malignancy means that it must not be ignored. This article outlines the
      diagnostic procedures relevant to haematuria, such that serious causes of
      bleeding are identified and treatment may be initiated.

PMID- 8564183
TI  - Clinical features and management of carcinoma of the pancreas.
AB  - Carcinoma of the pancreas remains a disease of uncertain aetiology, late
      presentation and appalling prognosis. This article reviews the clinical
      presentation of the disease and the role of surgical and non-surgical methods of
      management.

PMID- 8564184
TI  - Anaesthesia for heart transplantation.
AB  - As the number of heart transplantation recipients continues to grow, more cardiac
      centres are performing heart transplantation and more anaesthetists need to be
      trained for this exciting and challenging field of anaesthesia. This articles
      looks at the anaesthetic management of both the heart donor and the heart
      recipient.

PMID- 8564185
TI  - Phenformin-induced lactic acidosis: an almost forgotten complication of treatment
      with biguanides.

PMID- 8564186
TI  - A complication of monitoring in diabetes.

PMID- 8564187
TI  - GP fundholding: fact or fiction.
AB  - GP fundholding was introduced in 1991 as a part of the NHS reforms of that time.
      GPs were allowed to control their own budget to see if this act as an incentive
      for control of a few problem areas, e.g. outpatient referrals and non-emergency
      treatments. This article considers the effects of fundholding so far, and
      considers its future.

PMID- 8564188
TI  - A testing time.

PMID- 8564189
TI  - First W.D.M. Paton Memorial Lecture. An F4-vescent episode: Sir Henry Dale's
      laboratory 1919-1942.

PMID- 8564190
TI  - Lens opacification by antioestrogens: tamoxifen vs ICI 182,780.
AB  - The antioestrogen, tamoxifen, blocks volume-regulated chloride channels and
      reduces transparency in bovine lenses maintained in vitro. In contrast to
      tamoxifen, the steroidal antioestrogen, ICI 182780, did not block volume
      regulated chloride currents in three cultured cell lines and required 10 fold
      higher concentration to induce significant opacification of bovine lenses
      maintained in vitro. These data suggest that ocular toxic side effects will be
      minimized by use of the steroidal (ICI 182780) rather than nonsteroidal
      antioestrogens (tamoxifen).

PMID- 8564191
TI  - Assessment of renal dopaminergic system activity during cyclosporine A
      administration in the rat.
AB  - 1. Administration of cyclosporine A (CsA; 50 mg kg-1 day-1, s.c.) for 14 days
      produced an increase in both systolic (SBP) and diastolic (DBP) blood pressure by
      60 and 25 mmHg, respectively. The urinary excretion of dopamine, DOPAC and HVA
      was reduced from day 5-6 of CsA administration onwards (dopamine from 19 to 46%,
      DOPAC from 16 to 48%; HVA from 18 to 42%). In vehicle-treated rats, the urinary
      excretion of dopamine and DOPAC increased (from 7 to 60%) from day 5 onwards; by
      contrast, the urinary excretion of HVA was reduced (from 27 to 60%) during the
      second week. 2. No significant difference was observed between the Vmax and Km
      values of renal aromatic L-amino acid decarboxylase (AAAD) in rats treated with
      CsA for 7 and 14 days or with vehicle. 3. Km and Vmax of monoamine oxidase types
      A and B did not differ significantly between rats treated with CsA for 7 and 14
      days or with vehicle. 4. Maximal catechol-O-methyltransferase activity (Vmax) in
      homogenates of renal tissues obtained from rats treated with CsA for 7 or 14 days
      was significantly higher than that in vehicle-treated rats; Km (22.3 +/- 1.5
      microM) values for COMT did not differ between the three groups of rats. 5. The
      accumulation of newly-formed dopamine and DOPAC in cortical tissues of rats
      treated with CsA for 14 days was three to four times higher than in controls. The
      outflow of both dopamine and DOPAC declined progressively with time and reflected
      the amine and amine metabolite tissue contents. No significant difference was
      observed between the DOPAC/dopamine ratios in the perifusate of renal tissues
      obtained from CsA- and vehicle-treated rats. In addition, no significant
      differences were observed in k values or in the slope of decline of both DA and
      DOPAC between experiments performed with CsA and vehicle-treated animals. 6. The
      Vmax for the saturable component of L-3,4-dihydroxyphenylalanine (L-DOPA) uptake
      in renal tubules from rats treated with CsA was twice that of vehicle-treated
      animals. Km in CsA- and vehicle-treated rats did not differ. 7. The decrease in
      the urinary excretion of sodium and an increase in blood pressure during CsA
      treatment was accompanied by a reduction in daily urinary excretion of dopamine.
      This appears to result from a reduction in the amount of L-DOPA made available to
      the kidney and does not involve changes in tubular AAAD, the availability of
      dopamine to leave the renal cells and dopamine metabolism. The enhanced ability
      of the renal tissues of CsA-treated animals to synthesize dopamine, when
      exogenous L-DOPA is provided, results from an enhanced activity of the uptake
      process of L-DOPA in renal tubular cells.

PMID- 8564192
TI  - Effects of Ca2+ channel blockers on cortical hypoperfusion and expression of c
      Fos-like immunoreactivity after cortical spreading depression in rats.
AB  - 1. We examined the effects of two Ca2+ channel blockers, lomerizine (KB-2796) and
      flunarizine, on the cortical hypoperfusion (measured by hydrogen clearance and
      laser Doppler flowmetry methods) and cortical c-Fos-like immunoreactivity that
      follow KCl-induced cortical spreading depression in anaesthetized rats. Cortical
      spreading depression was induced by application of 1 M KCl for 30 s to the
      cortical surface, 3.0 mm posterior to the area of cerebral blood flow
      measurement. 2. In control rats, KB-2796 (0.3 and 1 mg kg-1, i.v.) dose
      dependently increased cerebral blood flow significantly at 30 min and 15 min,
      respectively, after its administration. Flunarizine (1 mg kg-1, i.v.)
      significantly increased cerebral blood flow 15 min after its administration. In
      contrast, dimetotiazine (3 mg kg-1, i.v.), a 5-HT2 and histamine H1 antagonist,
      failed to affect cerebral blood flow significantly. 3. After KCl application to
      the cortex, cerebral blood flow monitored by the laser Doppler flowmetry method
      increased transiently, for a few minutes, then fell and remained approximately 20
      to 30% below control for at least 60 min. Cerebral blood flow monitored by the
      hydrogen clearance method was also approximately 20 to 30% below baseline for at
      least 60 min after KCl application. KB-2796 (0.3 and 1 mg kg-1, i.v.) and
      flunarizine (1 and 3 mg kg-1, i.v.) administered 5 min before KCl application
      inhibited the cortical hypoperfusion that followed KCl application, but
      dimetotiazine (1 and 3 mg kg-1, i.v.) did not. 4. An indicator of neuronal
      activation, c-Fos-like immunoreactivity, was detected in the ipsilateral, but not
      in the contralateral frontoparietal cortex 2 h after KCl application. No c-Fos
      like immunoreactivity was seen on either side of the brain in the hippocampus,
      thalamus, striatum or cerebellum. 5. KB-2796 (1 mg kg-1, i.v.) and flunarizine (3
      mg kg-1, i.v.), but not dimetotiazine (3 mg kg-1, i.v.), significantly attenuated
      the expression of c-Fos-like immunoreactivity in the ipsilateral frontoparietal
      cortex. 6. These findings suggest that the inhibitory effects of KB-2796 and
      flunarizine on the cortical hypoperfusion and expression of c-Fos-like
      immunoreactivity induced by spreading depression are mediated via the effects of
      Ca(2+)-entry blockade, which may include an increase in cerebral blood flow and
      the prevention of excessive Ca2+ influx into brain cells. KB-2796 and flunarizine
      may prove useful as inhibitors of cortical spreading depression in migraine.

PMID- 8564193
TI  - Evidence for the presence of endothelin ETA receptors in endothelial cells in
      situ on the aortic side of porcine aortic valve.
AB  - 1. In the present study, we determined whether ETA receptors are present on
      endothelial cells in situ, by use of front-surface fluorometry of fura-2-loaded
      porcine aortic valvular strips and reverse transcription polymerase chain
      reaction (RT-PCR). 2. Although endothelin-1 (ET-1) and endothelin-3 (ET-3)
      induced maximum elevations of cytosolic Ca2+ concentrations ([Ca2+]i) at 10(-7)
      M, the peak elevations of [Ca2+]i induced by ET-1 were much greater than those
      induced by ET-3. 3. The application of ET-1 after ET-3 induced an additional
      increase in [Ca2+]i, while the application of ET-3 after ET-1 had no effect. A
      selective ETA receptor antagonist, BQ-123, partially inhibited the ET-1-induced
      Ca2+ transient but had no effect on ET-3-induced Ca2+ transients. These
      experiments indicated the presence of functioning ETA receptors in addition to
      ETB receptors in endothelial cells in situ. 4. The sequence of pig lung ETA
      receptor complimentary DNA (cDNA) was determined by PCR. RT-PCR, using specific
      primers for pig ETA receptor sequence and total RNA from endothelial cells on the
      aortic side of the aortic valve, gave the expected size of band. This PCR product
      was sequenced and was found to be identical to the sequence of the pig lung ETA
      receptor. 5. The partial sequence of the pig lung ETB receptor was also
      determined. RT-PCR for the pig ETB receptor revealed that endothelial cells of
      the aortic valve express ETB receptor messenger RNA (mRNA). 6. We confirmed that
      functioning ETA receptors and expression of ETA receptor mRNA exist in the
      endothelial cells on the aortic side of porcine aortic valves.

PMID- 8564194
TI  - Antihypertensive effect of an endothelin receptor antagonist in DOCA-salt
      spontaneously hypertensive rats.
AB  - 1. Endothelin-1 gene expression is enhanced in aorta and mesenteric arteries, and
      possibly other vessels, of deoxycorticosterone acetate (DOCA)-salt hypertensive
      rats but is normal or reduced in spontaneously hypertensive rats (SHR). Bosentan,
      a mixed ETA/ETB endothelin receptor antagonist, blunts the development of
      elevated blood pressure of DOCA-salt hypertensive rats but not in SHR. In this
      study we investigated whether treatment of DOCA-salt SHR with bosentan would
      result in blunted rise in blood pressure. 2. SHR, aged 13 weeks, were implanted
      with silastic containing DOCA and offered 1% saline to drink. Systolic blood
      pressure was measured by the tail-cuff method. Endothelin-1 mRNA abundance in
      aorta and mesenteric arteries was measured by Northern blot analysis. Content of
      immunoreactive endothelin in blood vessels was measured by radioimmunoassay. 3.
      Systolic blood pressure rose less in bosentan-treated DOCA-salt SHR (to 223 +/- 2
      mmHg) in comparison to the untreated rats (241 +/- 1), a small but significant
      difference (P < 0.001). However, blood pressure of bosentan-treated DOCA-salt SHR
      was still higher than in age-matched SHR. Endothelin-1 mRNA abundance and content
      of immunoreactive endothelin were increased in the aorta and the mesenteric
      arterial bed of DOCA-salt SHR, and were unaffected by treatment with bosentan. 4.
      These data support the hypothesis of a role of endothelin-1 in blood pressure
      elevation in this hypertensive model with malignant hypertension. They also
      support the hypothesis that an antihypertensive effect of the mixed ETA/ETB
      endothelin receptor antagonist, bosentan, is found when experimental hypertensive
      animals exhibit enhanced endothelin-1 gene expression in blood vessels.

PMID- 8564195
TI  - Leukotriene receptors on human pulmonary vascular endothelium.
AB  - 1. Cysteinyl-leukotrienes cause contractions and/or relaxations of human isolated
      pulmonary vascular preparations. Although, the localization and nature of the
      receptors through which these effects are mediated have not been fully
      characterized, some effects are indirect and not mediated via the well-described
      LT1 receptor. 2. In human pulmonary veins (HPV) with an intact endothelium,
      leukotriene D4 (LTD4) induced contraction above basal tone. This response was
      observed at lower concentrations of LTD4 in the presence of nitric oxide synthase
      inhibitor N omega-nitro-L-arginine (L-NOARG). Contractions (in the absence and
      presence of L-NOARG) were partially blocked by the LT1 antagonists (MK 571 and
      ICI 198615). 3. LTD4 relaxed HPV previously contracted with noradrenaline. This
      relaxation was potentiated by LT1 antagonists, but was abolished by removal of
      the endothelium. LTD4 also relaxed human pulmonary arteries (HPA) precontracted
      with noradrenaline but this effect was not modified by LT1 antagonists. 4. The
      results suggest that contraction of endothelium-intact HPV by LTD4 is partially
      mediated via LT1 receptors. Further, in endothelium-intact HPV, this contraction
      was opposed by a relaxation induced by LTD4, dependent on the release of nitric
      oxide, which was mediated, at least in part, via a non-LT1 receptor. In addition,
      LTD4 relaxation on contracted HPA was not mediated by LT1 receptors. 5. The
      mechanical effects of LTD4 on human pulmonary vasculature are complex and involve
      both direct and indirect mechanisms mediated via at least two types of cysteinyl
      leukotriene receptors.

PMID- 8564196
TI  - Pharmacological characterization of two novel and potent 5-HT4 receptor agonists,
      RS 67333 and RS 67506, in vitro and in vivo.
AB  - 1. The pharmacology of two novel 5-HT4 receptor agonists, RS 67333 (1-(4-amino-5
      chloro-2-methoxy-phenyl)-3-[1(n-butyl)-4-piperidinyl]-1- propanone HCl) and RS
      67506 (1-(4-amino-5-chloro-2-methoxy-phenyl)-3-[1-(2-methyl sulphonylamino)ethyl
      4-piperidinyl]-1-propanone HCl) have been assessed in vitro and in vivo. 2. RS
      67333 and RS 67506 exhibited affinities (pKi = 8.7 and 8.8, respectively) for the
      5-HT4 binding sites, labelled with [3H]-GR 113808, in guinea-pig striatum. The
      Hill coefficients from these displacement curves were not significantly different
      from unity. The compounds exhibited lower affinities (< 6.0) at several other
      receptors including 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2C, dopamine D1, D2 and
      muscarinic M1-M3 receptors. However, RS 67333 and RS 67506 did exhibit affinities
      for the sigma 1 (pKi = 8.9 and 7.9, respectively) and sigma 2 (pKi = 8.0 and 7.3,
      respectively) binding sites. 3. At the 5-HT4 receptor mediating relaxation of the
      carbachol-precontracted oesophagus, RS 67333 and RS 67506 acted as potent (pEC50
      8.4 and 8.6, respectively), partial agonists (intrinsic activities, with respect
      to 5-HT were 0.5 and 0.6, respectively) with respect to 5-HT. Relaxant responses
      to RS 67333 or RS 67506 were surmountably antagonized by GR 11308 (10 nM), with
      apparent affinities (pKB) of 9.1 and 9.0, respectively. RS 67333 and RS 67506
      induced dose-dependent increases in heart rate of the anaesthetized micropig
      (ED50 4.9 and 5.4 micrograms kg-1, i.v.), with maximal increases of 35 and 47
      beats min-1, respectively. 4. RS 67333 and RS 67506, therefore, acted as potent,
      partial 5-HT4 receptor agonists in vitro and in vivo. These compounds, by virtue
      of their high potency and selectivity, may have some utility in elucidating the
      physiological role of 5-HT4 receptors.

PMID- 8564197
TI  - Inhibition of volume-activated chloride currents in endothelial cells by
      chromones.
AB  - 1. We have studied the effects of the reported chloride channel blocker, sodium
      cromoglycate, on volume-activated Cl- currents in endothelial cells from bovine
      pulmonary artery by means of the whole-cell patch clamp technique. Cl- currents
      were activated by challenging the cells with a hypotonic extracellular solution
      of 60% of the normal osmolarity. 2. Half maximal activation of the current at +95
      mV occurred after exposure of the cells for 148 +/- 10 s (n = 6) to hypotonic
      solution (HTS). At the same membrane potential but in the presence of 100 microM
      sodium cromoglycate (disodium-1,3-bis (2'-carboxylate-chromone-5'-yloxy)-2
      hydroxy-propane) activation was delayed (253 +/- 25 s, n = 6) and the maximal
      current amplitude was reduced to 63 +/- 7% of the control (n = 13). 3. In
      comparison, an equimolar concentration of NPPB (5-nitro-2(3-phenyl) propylamino
      benzoic acid), another Cl- channel blocker, completely blocked the volume
      activated current in less than 20 s. 4. Sodium cromoglycate, applied at the time
      when the HTS-induced current was completely activated, dose-dependently inhibited
      this current with a concentration for half maximal inhibition of 310 +/- 70
      microM. Data for nedocromil sodium were not significantly different from those
      for sodium cromoglycate. 5. Sodium cromoglycate, loaded into the endothelial
      cells via the patch pipette in ruptured patches, resulted in a decline of the HTS
      activated current with a time course that was compatible with diffusion of the
      compound from the pipette into the cell. Intracellulary applied sodium
      cromoglycate was also more effective and at 50 microM caused a decrease in the
      amplitude of the current to 25 +/- 6% (n = 10) of the control current.6 It is
      concluded that blockade of volume-activated Cl- currents by extracellular sodium
      cromoglycatemay be due to an intracellular action following its permeation across
      the cell membrane.

PMID- 8564199
TI  - Quinidine blockade of the carbachol-activated nonselective cationic current in
      guinea-pig gastric myocytes.
AB  - 1. In guinea-pig gastric myocytes isolated from the antral circular layer,
      stimulation of muscarinic receptors by carbachol (CCh) induces a cationic current
      (ICCh) which is known as the main mechanism of depolarization induced by
      muscarinic stimulation. 2. We tested the effects of a number of ion channel
      blockers on ICCh and focused upon quinidine which was a highly potent blocker.
      Externally applied quinidine suppressed ICCh (IC50 = 0.25 microM) in a reversible
      and voltage-dependent manner. Applied internally, quinidine was about 100 times
      less potent than when applied externally. Persistent activation of G-protein by
      GTP gamma S also induced a cationic current similar to ICCh and this current was
      also blocked by quinidine. 4-Aminopyridine and tetraethylammonium also suppressed
      ICCh in a dose-dependent manner (IC50 = 3.3 mM and 4.1 mM, respectively). 3.
      Pretreatment with quinidine (2 microM) selectively blocked the acetylcholine
      (ACh)-induced depolarization which was recorded in the multicellular tissues by a
      conventional intracellular microelectrode technique. 4. Voltage-dependent K
      currents were also suppressed by quinidine but in a higher concentration range
      (IC50 = 3 microM). Quinidine, 10 microM, decreased the amplitude of the voltage
      dependent Ca current to only a small extent (15% decrease at 0 mV). Quinidine, 2
      microM, also suppressed only a minute proportion of the Ca-activated K current
      (11.1% decrease at 45 mV). 5. From these experiments, it is concluded that some
      organic agents known as K channel blockers are able to block the CCh-activated
      cation channel in a non-specific manner and among them, quinidine can be used as
      an effective blocker for ICCh in guinea-pig gastric myocytes.

PMID- 8564198
TI  - Investigation of the actions of chloroethylclonidine in rat aorta.
AB  - 1. The interaction between chloroethylclonidine (CEC) and noradrenaline (NA) has
      been examined at alpha-adrenoceptors mediating contractions of rat aorta. 2. In
      rat aorta, the competitive antagonist prazosin, over the concentration-range 0.01
      10 microM, produced concentration-dependent shifts in the contractile potency of
      NA, so that there was no component of the NA contraction resistant to prazosin.
      3. The irreversible alpha 1-adrenoceptor antagonists, phenoxybenzamine (PBZ) (1
      10 microM) and benextramine (10 microM) produced shifts in potency of NA and
      reduced the maximum response in a concentration-dependent manner. 4. The
      irreversible alpha 1-adrenoceptor antagonist, CEC (100 microM), produced a non
      parallel shift in the NA concentration-response curve so that low concentrations
      of NA produced relatively small contractions but relatively high concentrations
      produced further contractions, so that the maximum response was not significantly
      reduced. 5. The combination of CEC pretreatment and subsequent prazosin (0.1
      microM) produced a parallel shift in the potency of NA. However, prazosin (10
      microM) failed to produce any further effect on the response to high
      concentrations of NA following CEC pretreatment. Hence, a component of the
      contraction to NA in the presence of CEC was resistant to subsequent prazosin.
      Likewise, this component was resistant to a combination of prazosin (10 microM)
      and yohimbine (10 microM). 6. Receptor protection experiments were carried out in
      which tissues were exposed to NA (100 microM), yohimbine (10 microM) or prazosin
      (0.1 microM) prior to and during exposure to CEC. Receptor protection with NA,
      yohimbine or prazosin (0.1 microM), followed by washout prevented the shift in
      potency of NA produced by CEC. 7. Further experiments examined the effects of
      prazosin (10 microM) on responses to NA following receptor protection with NA
      (100 microM), yohimbine (10 microM), prazosin (10 microM), or xylazine (100
      microM). In receptor protection studies with NA, subsequent prazosin (10 microM)
      produced a shift in response to NA following CEC which was not signficantly
      different from the shift produced by prazosin alone in the absence of receptor
      protection. In receptor protection studies with prazosin, yohimbine or xylazine,
      subsequent prazosin (10 microM) produced shifts in the response to NA following
      CEC which were significantly less than the shift produced by prazosin alone in
      the absence of receptor protection.8. It is concluded that CEC has two actions in
      the rat aorta. Firstly, it behaves as an irreversible a,-adrenoceptor antagonist,
      reducing the response to low concentrations of NA (up to 10 microM).
      However,after exposure to CEC, concentrations of NA of 10 microM and above
      produced contractions resistant toprazosin. This resistant component was still
      present following receptor protection with alpha1,- or alpha2-adrenoceptor
      antagonists, but absent following receptor protection with NA. Hence, the latter
      response may represent an irreversible agonist interaction between CEC, NA and
      alpha-adrenoceptors which cannot be affected by subsequent competitive
      antagonism, but which can be prevented by receptor protection with the agonist NA
      prior to CEC.

PMID- 8564200
TI  - Synergy between the inositol phosphate responses to transfected human adenosine
      A1-receptors and constitutive P2-purinoceptors in CHO-K1 cells.
AB  - 1. The effect of adenosine A1-receptor and P2-purinoceptor agonists on [3H]
      inositol phosphate accumulation has been investigated in CHO-K1 cells transfected
      with the human adenosine A1-receptor. 2. Adenosine receptor agonists stimulated
      [3H]-inositol phosphate accumulation in CHO-K1 cells with a rank potency order of
      N6-cyclopentyladenosine (CPA) > 5'-N-ethylcarboxamidoadenosine (NECA) > 2
      chloroadenosine > N6-2-(4-aminophenyl) ethyladenosine (APNEA). The responses to
      both CPA and APNEA were antagonized by the A1 selective antagonist, 1,3
      dipropylcyclopentylxanthine (DPCPX) yielding KD values of 1.2 nM and 4.3 nM
      respectively. 3. ATP, UTP and ATP gamma S were also able to stimulate [3H]
      inositol phosphate accumulation in these cells with EC50 values of 1.9 microM,
      1.3 microM and 5.0 microM respectively. 2-Methyl-thio-ATP was a weak agonist of
      this response (EC50 > 100 microM). 4. The [3H]-inositol phosphate response to CPA
      was completely attenuated by pertussis toxin treatment (24 h; 100 ng ml-1). In
      contrast, the responses to ATP, UTP and ATP gamma S were only reduced by circa
      30% in pertussis toxin-treated cells. 5. The simultaneous addition of CPA and
      either ATP, UTP or ATP gamma S produced a large augmentation of [3H]-inositol
      phospholipid hydrolysis. This was due to an increase in the maximal response and
      was significantly greater than the predicted additive response for activation of
      these two receptor systems. The synergy was not observed in pertussis toxin
      treated cells. 6. No synergy was observed between the [3H]-inositol phosphate
      responses to histamine and ATP in CHO-K1 cells transfected with the bovine
      histamine H1-receptor. In these cells the response to histamine was completely
      resistant to inhibition by pertussis toxin treatment. 7. This study provides a
      clear demonstration of a synergy between pertussis toxin-sensitive and
      insensitive receptor systems in a model cell system which is an ideal host for
      transfected cDNA sequences. This model system should provide a unique opportunity
      to unravel the mechanisms underlying this example of receptor cross-talk
      involving phospholipase C.

PMID- 8564201
TI  - Neuroprotective properties of lifarizine compared with those of other agents in a
      mouse model of focal cerebral ischaemia.
AB  - 1. Changes in the peripheral type benzodiazepine binding site density following
      middle cerebral artery occlusion in the mouse, have been used as a marker of
      neuronal damage. These sites can be identified using the selective ligand [3H]-PK
      11195 located on non neuronal cells, macrophages and astroglia, within the CNS.
      Glial cell proliferation and macrophage invasion is an unvoidable sequelae to
      cerebral ischaemic injury, secondary to neuronal loss. Following occlusion of the
      left middle cerebral artery (left MCA) a reproducible lesion was found in the
      parietal cortex within 7 days which gave rise to a significant increase in [3H]
      PK 11195 binding. 2. Treatment of animals with the sodium channel blocker,
      lifarizine, significantly reduced the ischaemia-induced increase in [3H]-PK 11195
      binding when given either 30 min pre-ischaemia and three times daily for 7 days
      at 0.5 mg kg-1, i.p. (P < 0.01) or delayed until 15 min post-ischaemia and three
      times daily for 7 days at 0.5 mg kg-1, i.p. (P < 0.001). Lifarizine was an
      effective neuroprotective agent in this model of focal ischaemia in the mouse. 3.
      Lifarizine also showed a dose-related protection against the ischaemia-induced
      increase in [3H]-PK 11195 binding with significant protection at doses of 0.1 mg
      kg-1, i.p. (P < 0.05), 0.25 mg kg-1, i.p. (P < 0.01) or 0.5 mg kg-1, i.p. (P <
      0.01) 15 min post-ischaemia and b.i.d. for 7 days. No significant change is seen
      in the Kd for [3H]-PK 11195. The first dose could be delayed for up to 4 h after
      cerebralartery cauterization and protection was maintained.4. Phenytoin (28 mg kg
      1, i.v. 15 min and 24 h post-ischaemia) was also neuroprotective in this
      model(P<0.01). This agent is thought to interact with voltage-dependent sodium
      channels to effect its anticonvulsantactions and this mechanism may also underlie
      its neuroprotective actions in focal cerebralischaemia.5. Agents with other
      mechanisms of action were also shown to have significant neuroprotection in this
      model. The non-competitive NMDA antagonist, MK 801, showed significant
      neuroprotection in the model when given at 0.5 mg kg-1, i.p. 30 min pre-ischaemia
      with t.i.d. dosing for 7 days (P< 0.001). The dihydropyridine calcium antagonist,
      nimodipine was not protective when given using the same dosing protocol as MK
      801, 0.5 mg kg-1 30 min pre-occlusion and three times daily for 7 days but showed
      significant protection when given at 0.05 mg kg-1 15 min post-ischaemia and three
      times daily for 7days. The lipid peroxidation inhibitor, tirilazad (single dose 1
      mg kg-1, i.v.) showed significant neuroprotection when given 5 min post-ischaemia
      but not when the first dose was delayed for 4 h.

PMID- 8564202
TI  - Effects of IZP-94005 (contignasterol) on antigen-induced bronchial responsiveness
      in ovalbumin-sensitized guinea-pigs.
AB  - 1. We have investigated the novel naturally occurring marine compound, IZP-94005
      (contignasterol), as a potential anti-asthma agent, using both in vivo and in
      vitro models of allergen-induced bronchoconstriction and airway smooth muscle
      contraction. 2. Tracheal rings from ovalbumin (OA)-sensitized guinea-pigs were
      treated with various concentrations of IZP-94005 for 20 min prior to challenge
      with ovalbumin. IZP-94005 (3-30 microM) inhibited responses of sensitized
      tracheal rings stimulated with OA in a concentration-dependent manner, with an
      IC50 of 10 microM. 3. IZP-94005 (10 microM) had no effect on carbachol-induced
      contractions of sensitized guinea-pig tracheal rings, although it did inhibit
      histamine-induced responses of OA sensitized guinea-pig tracheal rings. 4. The
      effects of IZP-94005 in vivo were examined using OA-sensitized guinea-pigs which
      were tracheotomized under anaesthesia and placed in a body plethysmograph.
      Measurements of lung resistance and compliance were performed by isovolumetric
      analysis of volume and trans-pulmonary pressure. 5. IZP-94005 (50 and 200
      micrograms kg-1), by inhalation 20 min prior to OA challenge caused significant
      inhibition of the increase in lung resistance induced by OA in sensitized guinea
      pigs, compared to vehicle-treated animals. Nedocromil sodium (20 mg kg-1), with a
      similar protocol, also inhibited OA-induced responses in this model. 6. We
      therefore suggest that IZP-94005 is a good candidate for further investigation as
      a possible antiasthma agent.

PMID- 8564203
TI  - Reduction by lifarizine of the neuronal damage induced by cerebral ischaemia in
      rodents.
AB  - 1. The objective of this study was to evaluate the broad neurocytoprotective
      potential of the novel sodium-calcium ion channel modulator, lifarizine (RS
      87476), in two rodent 72 h survival models of forebrain ischaemia. 2. Under
      fluothane anaesthesia, rats were subjected to 10 min four vessel occlusion and
      gerbils to either (i) 5 or (ii) 10 min bilateral carotid artery occlusion. 3.
      Rats were dosed parenterally solely post-ischaemia (reperfusion) in a series of
      five studies covering a range of intra-arterial/intraperitoneal (i.a./i.p.)
      combination doses from 2/10, 5/20, 20/100, 50/200 and 100/500 micrograms kg-1,
      where the initial loading dose was injected i.a. at 5 min. An i.p. dose was given
      at 15 min and repeated twice daily. In a sixth study, treatment at 50/200
      micrograms kg-1 was deferred for 1 h. 4. Gerbils were treated (i) 15 min pre
      ischaemia with either (a) 250, (b) 500 micrograms kg-1 i.p., or (c) 5 mg kg-1 by
      gavage (p.o.) for 3 days then at 1 h pre-ischaemia. Animals treated as (ii)
      received 500 micrograms kg-1 i.p. 15 min pre-ischaemia. The above doses were
      repeated twice daily for 3 days post-ischaemia for the respective groups. 5. In
      rats, the protective effect of lifarizine was regionally and cumulatively
      assessed in six brain regions (anterior and posterior neocortex, hippocampal CA1
      subfield, thalamus, striatum, cerebellar Purkinje cells-brain stem) at each dose
      level. Cumulative (total) means +/-s.e.mean neurohistopathological scores(0-4) of
      1.16+/-0.09 (n=5), 1.02+/-0.10 (n=5), 0.93+/-0.06 (n=6), 0.79+/-0.09 (n=9) and
      0.45+/-0.16(n = 7), respectively, were obtained for the above treatment groups
      compared to the control (2.01 +/- 0.17,n = 16) group (P<0.0035). The score for
      the 1 h deferred treatment group was also significant at 0.77 +/- 0.10, n =5 (P<
      0.0035). The normal group without ischaemia showed a score of 0.52 +/- 0.09 (n =
      6).6. In gerbils, (i) percentage delayed neuronal death (DND) of hippocampal
      pyramidal cells in the CA1subfield was prevented at 250 (a) and 500 microg kg-'
      i.p. (b) (27.2+/- 14.6, n=6 and 26.9+/- 10.4%, n= 10 respectively, P<0.02)
      compared to controls (78.3+/-8.5%, n= 12) and by 5 mg kg-1 p.o. (c) (2.9+/-0.8%,n
      =l1, P <0.002). Mean +/- s.e.mean total brain scores (0-4) for each of 4
      different features denoting cerebral 'oedema' were lower for normal brains (1.60
      +/-0.34, n =6) and reduced in animals dosed at 250(a) (3.00+/-0.79, n=6) and 500
      microg kg-1 i.p. (b) (3.75 0.36, n= 10) compared to controls (6.58+/-1.00,n = 12)
      (P< 0.02 -0.03). There was a linear relationship (r = 0.97) between the 'oedema'
      scores and percentage CA1 DND. Percentage CA1 DND in response to 10 min ischaemia
      (ii) was reduced(53.0+/-21.0%, n=6, P<0.05) compared to controls (100.0+/-0.0%,
      n=7).7 The significant neuroprotection shown by lifarizine in rodents
      substantiates findings in other species.These observations, together with its
      effect on ion channels and efficacy at extremely low doses offers novelty and
      suggests a broad spectrum of activity in ischaemia.

PMID- 8564204
TI  - Ionic currents and inhibitory effects of glibenclamide in seminal vesicle smooth
      muscle cells.
AB  - 1. Whole-cell voltage-clamp recordings were made from smooth muscle cells
      isolated from guinea-pig seminal vesicle. 2. When the recording pipette solution
      contained 130 mM KCl and a low concentration of EGTA (0.2 mM), a dominant outward
      current was elicited by depolarization to positive of -30 mV from a holding
      potential of -50 mV. The current was non-inactivating, stimulated by
      intracellular Ca2+ and blocked by bath-applied 1 mM tetraethylammonium but not 1
      mM 3,4 diaminopyridine. 3. If 10 mM EGTA was added to the KCl pipette solution
      and the holding potential was -50 mV, or more negative, the major current
      elicited by depolarization to positive of -30 mV was an A-type K(+)-current. This
      current inactivated rapidly (within 100 ms) and was blocked by bath-applied 1 mM
      3,4-diaminopyridine but not 10 mM tetraethylammonium. 4. An inward voltage-gated
      Ca channel current was observed on depolarization to positive of -30 mV with 1.5
      mM Ca2+ or 10 mM Ba2+ in the bath solution and when Ca+ replaced K+ in the
      pipette. The Ba(2+)-current was shown to be abolished by bath-applied 100 microM
      Cd2+ and inhibited by 90% by 1 microM nifedipine, and thus appeared to be carried
      by L-type Ca channels. 5. High concentrations of glibenclamide (10-500 microM)
      inhibited A-type K(+)-current, Ba(2+)-current and contraction of the whole tissue
      induced by noradrenaline or electrical field stimulation. 6. From these data we
      suggest that seminal vesicle smooth muscle cells express Ca2+ -dependent K
      channels, A-type K channels and L-type Ca channels which are inhibited by
      tetraethylammonium,3,4-diaminopyridine and nifedipine, respectively. In addition,
      an unexpected relaxant effect of high concentrations of glibenclamide may be
      explained by inhibition of the Ca channels.

PMID- 8564205
TI  - Dietary calcium and magnesium supplements in spontaneously hypertensive rats and
      isolated arterial reactivity.
AB  - 1. High calcium diet attenuates the development of hypertension but an associated
      undesirable effect is that Mg2+ loss to the urine is enhanced. Therefore, we
      studied the effects of high calcium diet alone and in combination with increased
      magnesium intake on blood pressure and arterial function. 2. Forty-eight young
      spontaneously hypertensive rats (SHR) were allocated into four groups, the
      dietary contents of Ca2+ and Mg2+ being: 1.1%, 0.2% (SHR); 2.5%, 0.2% (Ca-SHR);
      2.5%, 0.8% (CaMg-SHR); and 1.1%, 0.8% (Mg-SHR), respectively. Development of
      hypertension was followed for 13 weeks, whereafter electrolyte balance,
      lymphocyte intracellular free calcium ([Ca2+]i), and mesenteric arterial
      responses in vitro were examined. Forty normotensive Wistar-Kyoto (WKY) rats were
      investigated in a similar manner. 3. Calcium supplementation comparably
      attenuated the development of Lypertension during normal and high magnesium
      intake in SHR, with an associated reduced lymphocyte [Ca2+]i and increased Mg2+
      loss to the urine. 4. Endothelium-dependent arterial relaxation to acetylcholine
      was augmented in Ca-SHR and CaMg-SHR, while the relaxations to isoprenaline and
      the nitric oxide donor SIN-1 were similar in all SHR groups. Relaxation responses
      induced by the return of K+ to the organ bath upon precontractions in K(+)-free
      solution were used to evaluate the function of arterial Na+, K(+)-ATPase. The
      rate of potassium relaxation was similar in Ca-SHR and CaMg-SHR and faster than
      in untreated SHR. 5. Contractile responses to high concentrations of potassium
      and noradrenaline, and the ability of vascular smooth muscle to sequester Ca2+,
      which was evaluated by eliciting responses to caffeine or noradrenaline after
      loading periods in different Ca2+ concentrations, were comparable in all SHR
      groups. In SHR with increased magnesium intake, and in WKY rats with calcium or
      magnesium supplementation, no detectable effects on blood pressure and arterial
      function were observed.6. In conclusion, high calcium diet attenuated the
      development of hypertension in SHR, with an associated augmented endothelium
      dependent relaxation, promoted recovery rate of ionic gradients across the cell
      membrane via Na+, K+-ATPase, and reduced basal [Ca2+ ]i. Dietary magnesium
      supplementation, whether combined with normal or high calcium intake, had no
      beneficial effects on blood pressure or arterial function.

PMID- 8564207
TI  - A comparison of the effects of selective metabotropic glutamate receptor agonists
      on synaptically evoked whole cell currents of rat spinal ventral horn neurones in
      vitro.
AB  - 1. Whole cell synaptic currents were recorded under voltage clamp from a total of
      54 ventral horn neurones held near to their resting potential by the patch clamp
      technique in immature rat spinal cord preparations in vitro. Twenty eight
      neurones were identified, by antidromic invasion from ventral roots, as
      motoneurones. Excitatory postsynaptic currents (e.p.s.cs) of peak amplitude -480
      pA +/- 66 s.e. mean and -829 +/- 124 pA were evoked respectively from the
      unidentified ventral horn neurones and the motoneurones in response to maximal
      activation of the segmental dorsal root. 2. The e.p.s.cs were depressed
      reversibly by the metabotropic glutamate agonists 1S3S-1-aminocyclopentane-1,3
      dicarboxylate (1S3S-ACPD) (EC50 17.1 microM +/- 0.3 s.e. mean, n = 14) and L-2
      amino-4-phosphonobutanoate (L-AP4) (EC50 = 2.19 +/- 0.19 microM, n = 15). Since
      both agonists independently produced more than 90% depression it is likely that
      the receptors that mediate their effects are present on the same presynaptic
      terminals. 3. When the Mg2+ concentration was raised from 0.75 mM to 2.75 mM
      together with the addition of 50 microM D-2-amino-5-phosphonopentanoate (AP5), a
      treatment which would increase the proportion of monosynaptic component in the
      e.p.s.c. the concentration-effect plots for both 1S3S-ACPD (EC50 1.95 +/- 0.4
      microM, n = 8) and L-AP4 (EC50 0.55 +/- 0.20 microM, n = 7) were shifted to the
      left, suggesting that monosynaptic e.p.cs of primary afferents to ventral horn
      neurones are more susceptible to L-AP4 and 1S3S-ACPD than are other synapses in
      polysynaptic pathways. 4. lS3S-ACPD (20 and 50 microM) also caused mean sustained
      inward currents of 95 +/- 31 pA (n = 6) and248 +/- 49 pA (n = 10) respectively.
      In the combined presence of AP5 (50 microM) and Mg2+ (2.75 mM) themean response
      to 50 microM lS3S-ACPD was reduced to 106+/- 18 pA (n = 4). In the presence of
      tetrodotoxin(1 microM) the corresponding value was 48 +/- 6 pA (n = 4). Similar
      sustained inward currents produced by N-methyl-D-aspartate (NMDA) were almost
      abolished to < 10 pA in the presence of AP5 and 2.75 mMMg2+. In the presence of
      tetrodotoxin the maximum inward current produced by NMDA was undiminished. Thus a
      large component of the excitatory action of lS3S-ACPD was mediated at non-NMDA
      receptors both directly at the patch-clamped neurones and indirectly by synaptic
      relay.

PMID- 8564206
TI  - The mechanism of action of alpha 2-adrenoceptors in human isolated subcutaneous
      resistance arteries.
AB  - 1. The effect of noradrenaline and the selective alpha 2-adrenoceptor agonist,
      azepexole, on tone and intracellular Ca2+ ([Ca2+]i) was examined in human
      isolated subcutaneous resistance arteries. Isolated arteries were mounted on an
      isometric myograph and loaded with the Ca2+ indicator, fura-2, for simultaneous
      measurement of force and [Ca2+]i. 2. High potassium solution (KPSS),
      noradrenaline and azepexole increased [Ca2+]i and contracted subcutaneous
      arteries in physiological saline. When extracellular Ca2+ was removed and the
      calcium chelator, BAPTA, added to the physiological saline (PSSo), responses to
      noradrenaline were transient and reduced, and responses to azepexole were
      markedly inhibited. 3. Ryanodine, an agent which interferes with Ca2+ release
      from intracellular stores, had little effect on contractile responses to KPSS,
      noradrenaline or azepexole in physiological saline. The response to caffeine in
      physiological saline was inhibited by ryanodine. In PSSo, ryanodine partially
      inhibited contractile responses to noradrenaline and azepexole, and completely
      abolished the response to caffeine. 4. Noradrenaline and azepexole both
      significantly increased maximum force achieved by cumulative addition of Ca2+ to
      a Ca(2+)-free depolarizing solution and shifted the calculated relationship
      between [Ca2+]i and force to the left, suggesting these agents increase the
      sensitivity of the contractile apparatus to [Ca2+]i. 5. (-)-202 791, a
      dihydropyridine antagonist of voltage-operated calcium channels partially
      inhibited both the contractile response and the rise in [Ca2+]i induced by
      azepexole. Pre-treatment of arteries with pertussis toxin inhibited responses to
      azepexole, but had no significant effect on tone induced by KPSS or
      noradrenaline. ETYA, an inhibitor of phospholipase A2, lipoxygenase and cyclo
      oxygenase, had no effect on azepexole-induced contraction in the presence of N
      omega nitro-L-arginine methyl ester.6. Azepexole, a selective alpha2-adrenoceptor
      agonist, contracts human subcutaneous resistance arteries by a mechanism largely
      dependent on the influx of extracellular Ca2", probably through voltage-operated
      calcium channels. This action involves a pertussis toxin-sensitive G protein,
      possibly Gi.

PMID- 8564208
TI  - The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and
      localization to specific prostatic cell types.
AB  - 1. Benign prostatic hyperplasia (BPH) causes urinary obstruction in aging men
      that frequently requires surgery to relieve the symptoms of urinary retention,
      nocturia, and micturition. Smooth muscle tone which contributes to the urethral
      constriction in the enlarged gland appears to be mediated by the alpha 1
      adrenoceptors. In this paper, molecular and pharmacological approaches are used
      to establish the role played by the alpha 1C-adrenoceptor subtype in the
      prostate. 2. The alpha 1-adrenoceptor subtype(s) expressed in human prostate were
      investigated by use of polymerase chain reaction (PCR), Northern blot, and in
      situ hybridization. The alpha 1C subtype was found in both prostate stromal and
      glandular cells while alpha 1B and alpha 1D subtypes were expressed in glandular
      cells. High expression levels for alpha 1C were observed in prostate cancer
      tissues in both stroma and glandular cells. 3. Full length alpha 1C-adrenoceptor
      cDNA was cloned from human prostate. Stable mammalian cell lines expressing human
      alpha 1B-, alpha 1C-, and alpha 1D-adrenoceptors were made. Membranes prepared
      from these cell lines and human prostate were used to evaluate the
      pharmacological profiles of human alpha 1B-, alpha 1C- and alpha 1D-adrenoceptors
      in comparison to human prostate. Leverage plot analysis of compound affinities
      determined by competition for [125I]-I-HEAT binding demonstrated that the alpha
      1C subtype is the predominant alpha 1-adrenoceptor in human prostate. 4. The
      alpha 1-adrenoceptors cause smooth muscle constriction by coupling to IP3
      turnover and intracellular Ca2+ release. Using stable cell lines to measure IP3
      production in response to noradrenaline, alpha 1C stimulated IP3 production most
      efficiently, with alpha 1B at an intermediate level, while little IP3 above
      background could be detected with alpha 1D. These results supported a functional
      role of the alpha 1C-adrenoceptor on prostate smooth muscle constriction by
      noradrenaline stimulation.

PMID- 8564209
TI  - Effects of type-selective phosphodiesterase inhibitors on glucose-induced insulin
      secretion and islet phosphodiesterase activity.
AB  - 1. We examined various type-selective phosphodiesterase (PDE) inhibitors on
      glucose-induced insulin secretion from rat isolated islets, on islet PDE activity
      and on islet cyclic AMP accumulation in order to assess the relationship between
      type-selective PDE inhibition and modification of insulin release. 2. The non
      selective PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 10(-5)-10(-3) M), as
      well as the type III selective PDE inhibitors SK&F 94836 (10(-5)-10(-3) M), Org
      9935 (10(-7)-10(-4) M), SK&F 94120 (10(-5)-10(-4) M) and ICI 118233 (10(-6)-10(
      4) M) each caused concentration-dependent augmentation (up to 40% increase) of
      insulin release in the presence of a stimulatory glucose concentration (10 mM),
      but not in the presence of 3 mM glucose. 3. Neither the type IV PDE inhibitor
      rolipram (10(-4) M) nor the type I and type V PDE inhibitor, zaprinast (10(-4)
      10(-3) M) modified glucose-induced insulin release when incubated with islets,
      although a higher concentration of rolipram (10(-3) M) inhibited secretion by
      55%. However, when islets were preincubated with these drugs followed by
      incubation in their continued presence, zaprinast (10(-6)-10(-4) M) produced a
      concentration-dependent inhibition (up to 45% at 10(-4) M). Under these
      conditions, rolipram inhibited insulin secretion at a lower concentration (10(-4)
      M) than when simply incubated with islets. 4. A combination of SK&F 94836 (10(-5)
      M) and forskolin (5 x 10(-8) M) significantly augmented glucose-induced insulin
      secretion (30% increase), although neither drug alone, in these concentrations,
      produced any significant effect. 5. Islet cyclic AMP levels, which were not
      modified by forskolin (10-6 M), SK&F 94836 (10-4 M) or Org 9935 (10-5 M) were
      significantly elevated (approximately 3.7 fold increase) by forskolin inc
      ombination with either SK&F 94836 or Org 9935.6 Homogenates of rat islets showed
      a low Km (1.7 microM) and high Km (13 microM) cyclic AMP PDE in the supernatant
      fractions (from 48,000 g centrifugation), whereas the particulate fraction showed
      only a low Km (1.4 microM) cyclic AMP PDE activity.7. The PDE activity of both
      supernatant and pellet fractions were consistently inhibited by SK&F94836 or Org
      9935, the concentrations required to reduce particulate PDE activity by 50% being
      5.5 and 0.05 microM respectively.8 Rolipram (10-5 10-4 M) did not consistently
      inhibit PDE activity in homogenates of rat islets and zaprinast (10-4 M)
      consistently inhibited activity by 30% in the supernatant fraction, but not
      consistently in the pellet.9 These data are consistent with the presence of a
      type III PDE in rat islets of Langerhans.

PMID- 8564210
TI  - Effect of KC399, a newly synthesized K+ channel opener, on acetylcholine-induced
      electrical and mechanical activities in rabbit tracheal smooth muscle.
AB  - 1. Effects of KC399, an opener of ATP-sensitive K+ channels were investigated on
      membrane potential, isometric force and intracellular Ca2+ ([Ca2+]i) mobilization
      induced by acetylcholine (ACh) in smooth muscle from the rabbit trachea. 2. In
      these smooth muscle cells, ACh (0.1 and 1 microM) depolarized the membrane in a
      concentration-dependent manner, KC399 (1-100 nM) hyperpolarized the membrane
      whether in the presence or absence of ACh. When the concentration of ACh was
      increased, the absolute values of the membrane potential induced by the maximum
      concentration of KC399 were less negative. 3. ACh (0.1 to 10 microM)
      concentration-dependently produced a phasic, followed by a tonic increase in both
      [Ca2+]i and force. KC399 (above 3 nM) lowered the resting [Ca2+]i and attenuated
      the ACh-induced phasic and tonic increases in [Ca2+]i and force, in a
      concentration-dependent manner. The magnitude of the inhibition was greater for
      the ACh-induced tonic responses than for the phasic ones. Nicardipine (0.3
      microM), a blocker of the L-type Ca2+ channel, attenuated the ACh-induced tonic,
      but not phasic, increases in [Ca2+]i and force. KC399 further attenuated the ACh
      induced tonic responses in the presence of nicardipine. 4. In beta-escin-skinned
      strips, Ca2+ (0.3-10 microM) produced a contraction in a concentration-dependent
      manner. KC399 (0.1 microM) had no effect on the Ca(2+)-force relationship in the
      presence or absence of ATP with GTP. However, at a very high concentration (1
      microM), this agent slightly shifted the relationship to the right and attenuated
      the maximum Ca(2+)-induced contraction. 5. We conclude that, in rabbit tracheal
      smooth muscle, the membrane hyperpolarization induced byKC399 attenuates the ACh
      induced tonic increase in [Ca2+], through an inhibition of nicardipinesensitive
      and -insensitive Ca2+-influxes, thus causing an inhibition of the ACh-induced
      tonic contraction. The ACh-induced phasic increase in [Ca2+]i and force are also
      inhibited, but less effectively than the tonic ones, suggesting that the action
      of such K+ channel openers on agonist-induced responses may be slightly different
      in tracheal from vascular smooth muscle.

PMID- 8564211
TI  - Inhibition by Zn2+ of uridine 5'-triphosphate-induced Ca(2+)-influx but not
      Ca(2+)-mobilization in rat phaeochromocytoma cells.
AB  - 1. Uridine 5'-triphosphate (UTP)-evoked increase in intracellular Ca2+
      concentration ([Ca]i) and release of dopamine were investigated in rat
      phaeochromocytoma PC12 cells. UTP (1-100 microM) evoked an increase in [Ca]i in a
      concentration-dependent manner. This response was decreased to about 30% by
      extracellular Ca(2+)-depletion, but not abolished. This [Ca]i rise was mimicked
      by 100 microM ATP but not by 100 microM 2-methyl-thio-ATP or alpha,beta-methylene
      ATP in the absence of external Ca2+, suggesting that the response was mediated by
      P2U purinoceptors, a subclass of P2-purinoceptors. 2. The UTP-evoked [Ca]i rise
      consisted of two components; a transient and a sustained one. When external Ca2+
      was removed, the sustained component was abolished while the transient component
      was decreased by about 70% but did not disappear. These results suggest that UTP
      induces Ca(2+)-mobilization and, subsequently, Ca(2+)-influx. 3. The UTP-evoked
      increase in [Ca]i was not affected by Cd2+ (100 and 300 microM) or nicardipine
      (30 microM), inhibitors of voltage-gated calcium channels, but was significantly
      inhibited by Zn2+ (10-300 microM) in the presence of external Ca2+. Zn2+,
      however, did not affect the Ca2+ response to UTP in the absence of external Ca2+.
      4. UTP (30 microM-1 mM) evoked the release of dopamine from the cells in a
      concentration-dependent manner. This dopamine release was abolished by Ca(2+)
      depletion or Zn2+ but not by Cd2+ or nicardipine. 5. Taken together, the data
      demonstrate that UTP stimulates P2U-purinoceptors and induces a rise in [Ca]i
      both by Ca(2+)-mobilization and Ca(2+)-influx in PC12 cells. The dopamine release
      evoked by UTP requires external Ca2+ which may enter the cells through pathways
      sensitive to Zn2+ but insensitive to Cd2+ or nicardipine.

PMID- 8564212
TI  - Inhibitory action of PPADS on relaxant responses to adenine nucleotides or
      electrical field stimulation in guinea-pig taenia coli and rat duodenum.
AB  - 1. The effect of pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) on
      the relaxant response to adenine nucleotides was examined in the carbachol
      contracted guinea-pig taenia coli and rat duodenum, two tissues possessing P2y
      purinoceptors. In addition, in the taenia coli PPADS was investigated for its
      effect on relaxations evoked by adenosine, noradrenaline and electrical field
      stimulation. In order to assess the selectivity of PPADS between P2-purinoceptor
      blockade and ectonucleotidase activity, its influence on ATP degradation was
      studied in guinea-pig taenia coli. 2. The resulting rank order of potency for the
      adenine nucleotides in guinea-pig taenia coli was: 2-methylthio ATP >> ATP >
      alpha,beta-methylene ATP with the respective pD2-values 7.96 +/- 0.08 (n = 23),
      6.27 +/- 0.12 (n = 21) and 5.88 +/- 0.04 (n = 24). 3. In guinea-pig taenia coli,
      PPADS (10-100 microM) caused a consistent dextral shift of the concentration
      response curve (CRC) of 2-methylthio ATP and ATP resulting in a biphasic Schild
      plot. A substantial shift was only observed at 100 microM PPADS, the respective
      pA2-values at this particular concentration were 5.26 +/- 0.16 (n = 5) and 5.15
      +/- 0.13 (n = 6). Lower concentrations of PPADS (3-30 microM) antagonized the
      relaxant effects to alpha,beta-methylene ATP in a surmountable manner. An
      extensive shift of the CRC was produced only by 30 microM PPADS (pA2 = 5.97 +/-
      0.08, n = 6), and the Schild plot was again biphasic. 4. The relaxant responses
      to electrical field stimulation (80 V, 0.3 ms, 5 s, 0.5-16 Hz) in guinea
      pigtaenia coli were concentration-dependently inhibited by PPADS (10-100
      microM).5. In guinea-pig taenia coli, the potency of ATP in inducing relaxation
      appeared to be independent of its rate of degradation by ecto-nucleotidases,
      since the Km-value (366 microM) obtained in the enzyme assay was much higher than
      the functional EC50-value (0.45 microM) of ATP. PPADS (3-100 microM) was only
      weakly active in inhibiting ecto-nucleotidase activity leaving a residual
      activity of 81.8 +/- 5.1% at 100 microM.Enzyme inhibition by PPADS was
      concentration-independent and non-competitive.6. In rat duodenum, the rank order
      of potency was: 2-methylthio ATP >ATP> >alpha,beta-methylene ATP,the respective
      pD2-values being 6.98 +/- 0.04 (n = 76), 6.26 +/- 0.02 (n = 6) and 4.83 +/- 0.02
      (n = 6). Among these agonists, 2-methylthio ATP displayed the lowest apparent
      efficacy.7. The CRC of 2-methylthio ATP in rat duodenum was shifted to the right
      by PPADS (10-100 microM) ina concentration-dependent manner, and Schild analysis
      gave a pA2-value of 5.09 +/- 0.06 (slope = 1.02,n=14).8 PPADS was without any
      effect on the carbachol-induced contraction in guinea-pig taenia coli or rat
      duodenum and on the relaxation to noradrenaline or adenosine in guinea-pig taenia
      coli.9 In conclusion, the antagonistic properties of PPADS at the taenia coli and
      rat duodenum P2y-purinoceptors were different from those recently described at
      the P2x-subtype: inhibition of P2y-purinoceptor-mediated responses was observed
      at higher concentrations (3-100 microM vs. 1-10 (30) microM).Furthermore, we
      conclude that in addition to the classical P2y-subtype, which is largely PPADS
      resistant,the guinea-pig taenia coli may be endowed with a distinct relaxation
      mediating P2-purinoceptor subtype which is sensitive to PPADS.

PMID- 8564213
TI  - Characterization of muscarinic receptors mediating contractions of circular and
      longitudinal muscle of human isolated colon.
AB  - 1. The effects of seven muscarinic receptor antagonists were used to characterize
      the receptors which mediate carbachol-evoked contractions of intertaenial
      circular and taenial longitudinal muscle in human isolated colon. The effects of
      these antagonists were studied upon colon contractions induced by cumulatively
      added carbachol which had mean EC50 values of 11.7 +/- 2.3 microM (n = 8) and
      12.6 +/- 2.3 microM (n = 8) respectively upon circular and longitudinal smooth
      muscle. 2. All antagonists displaced concentration-response curves to carbachol
      to the right in a parallel manner. The maximum concentration of each antagonist
      added (30 nM-10 microM) did not significantly suppress the maximum response. 3.
      In circular muscle, the M3 muscarinic receptor antagonists, 4-diphenylacetoxy-N
      methylpiperidine methiodide (4-DAMP), hexahydrosiladiphenidol (HHSiD) and para
      fluoro-hexahydrosiladiphenidol (p-F-HHSiD) inhibited responses with pA2 values of
      9.41 +/- 0.23, 7.17 +/- 0.07, 6.94 +/- 0.18 respectively. The M2 muscarinic
      receptor antagonist, AF-DX 116, the M2/M4 muscarinic receptor antagonist,
      himbacine, and the M1 muscarinic receptor antagonist, pirenzepine, yielded pA2
      values of 7.36 +/- 0.43, 7.47 +/- 0.14 and 7.23 +/- 0.48 respectively. The non
      selective antagonist, atropine, had a pA2 of 8.72 +/- 0.28. 4. In longitudinal
      muscle 4-DAMP, HHSiD, p-F-HHSiD, AF-DX 116, himbacine and pirenzepine gave pA2
      values of 9.09 +/- 0.16, 7.45 +/- 0.43, 7.44 +/- 0.21, 6.44 +/- 0.1, 7.54 +/-
      0.40, 6.87 +/- 0.38 respectively. Atropine yielded a pA2 value of 8.60 +/- 0.08.
      5. The pharmacological profile of antagonist affinities at the muscarinic
      receptor population responding to muscarinic agonist-evoked contraction is
      similar to that widely accepted as characterizing the activation of an M3
      muscarinic receptor subtype, although pA2 values of some antagonists are lower
      than that seen in other investigations.

PMID- 8564214
TI  - Endogenous nitric oxide signalling system and the cardiac muscarinic
      acetylcholine receptor-inotropic response.
AB  - 1. In this paper we have determined the different signalling pathways involved in
      muscarinic acetylcholine receptor (AChR)-dependent inhibition of contractility in
      rat isolated atria. 2. Carbachol stimulation of M2 muscarinic AChRs exerts a
      negative inotropic response, activation of phosphoinositide turnover, stimulation
      of nitric oxide synthase and increased production of cyclic GMP. 3. Inhibitors of
      phospholipase C, protein kinase C, calcium/calmodulin, nitric oxide synthase and
      guanylate cyclase, shifted the dose-response curve of carbachol on contractility
      to the right. These inhibitors also attenuated the muscarinic receptor-dependent
      increase in cyclic GMP and activation of nitric oxide synthase. In addition,
      sodium nitroprusside, isosorbide, or 8-bromo cyclic GMP, induced a negative
      inotropic effect, increased cyclic GMP and activated nitric oxide synthase. 4.
      These results suggest that carbachol activation of M2 AChRs, exerts a negative
      inotropic effect associated with increased production of nitric oxide and cyclic
      GMP. The mechanism appears to occur secondarily to stimulation of
      phosphoinositides turnover via phospholipase C activation. This in turn, triggers
      cascade reactions involving calcium/calmodulin and protein kinase C, leading to
      activation of nitric oxide synthase and soluble guanylate cyclase.

PMID- 8564215
TI  - Myocardial and coronary endothelial protective effects of acetylcholine after
      myocardial ischaemia and reperfusion in rats: role of nitric oxide.
AB  - 1. Recent experiments suggest that acetylcholine (ACh) may exert myocardial
      protective effects during ischaemia (I) and reperfusion (R). The present study
      was designed (i) to assess whether ACh limits infarct size and protects coronary
      endothelial cells in a rat model of I and R, (ii) to evaluate the role of ATP
      sensitive potassium (KATP) channels and nitric oxide (NO) in the beneficial
      effect of ACh (iii) to evaluate whether the protective effect of ACh also extends
      to coronary endothelial cells and (iv) to assess whether ACh contributes to the
      beneficial effect of preconditioning. 2. Anaesthetized rats were subjected to 20
      min I (left coronary artery occlusion) and 2 h of R. Infarct size was assessed by
      triphenyltetrazolium (TTC) staining and expressed as a % of the area at risk
      (India ink injection). Vascular studies were performed on 1.5-2 mm coronary
      segments (internal diameter 250-300 micros) removed distal to the site of
      occlusion and mounted in wire myographs. 3. ACh limited infarct size (from 59 +/-
      3 to 26 +/- 5%, P < 0.01), and this was prevented by atropine (46 +/- 7%; P <
      0.05 vs ACh), but not by the inhibitor of KATP channels, glibenclamide (29 +/-
      8%). The inhibitor of NO synthesis NG-nitro L-arginine did not affect infarct
      size (54 +/- 5%) but abolished the beneficial effect of ACh (59 +/- 8%; P < 0.05
      vs ACh), whereas the NO donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1
      limited infarct size to the same extent as ACh (28 +/- 6%). Preconditioning also
      limited infarct size (5 +/- 2%, P< 0.01 vs control), and this was not affected by
      atropine (6 +/- 2%). I and R induced a significant decrease in the endothelium
      dependent relaxations of isolated coronary arteries toACh (maximal response:
      sham: 58+/-4; I/R: 25+/-5%; P<0.01) and this dysfunction was prevented by prior
      in vivo treatment with ACh (55+/-7%; P<0.01 vs I/R) or (SIN-1 50+/-5%; P<0.05 vs
      I/R).4 Thus, in the rat model, ACh is able to stimulate potent endogenous
      protective mechanisms during I and R, which are evident both at the level of
      myocardial and coronary endothelial cells, and appear entirely mediated through
      the production of NO. Pharmacological stimulation of this endogenous protective
      mechanism may constitute a new approach in the treatment of acute myocaridal
      ischaemia.

PMID- 8564216
TI  - Evidence for selective inhibition by lysophosphatidylcholine of acetylcholine
      induced endothelium-dependent hyperpolarization and relaxation in rat mesenteric
      artery.
AB  - The effects of lysophosphatidylcholine (LPC) on acetylcholine-induced
      hyperpolarization and relaxation were examined in rat mesenteric arteries. LPC (3
      10 microM) reversibly inhibited endothelium-dependent hyperpolarization by
      acetylcholine in a concentration-dependent manner. LPC (10 microM) inhibited only
      partially endothelium-dependent relaxation by acetylcholine. However,
      acetylcholine-induced relaxation obtained in the presence of 100 microM NG-nitro
      L-arginine was almost completely eliminated by 10 microM LPC. These results
      indicate that LPC inhibits hyperpolarization and relaxation due to endothelium
      derived hyperpolarizing factor more specifically than the relaxation due to
      endothelium-derived nitric oxide.

PMID- 8564217
TI  - 5-HT3 receptor agonist induced carrier-mediated release of dopamine in rat
      striatum in vivo.
AB  - 1. In vivo microdialysis was used to study the effect of phenylbiguanide (PBG), a
      5-hydroxytryptamine3 receptor agonist, on the extracellular output of dopamine,
      3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5
      hydroxyindoleacetic acid (5-HIAA) in the corpus striatum. 2. PBG produced a dose
      related (10-500 microM) increase in the release of dopamine (280-2000%). DOPAC
      and HVA output decreased with the perfusion of PBG. This decrease was similar
      with 50-500 microM PBG. 5-HIAA output was not affected by any PBG concentration
      used. 3. When nomifensine (5 microM) was included in the Ringer solution, the
      effect of PBG on the release of dopamine was ameliorated or inhibited. However,
      the effect of PBG (50-500 microM) on the extracellular output of DOPAC and HVA
      was similar in the absence and in the presence of nomifensine (5 microM). 4.
      Perfusion of MDL 72222, a 5-hydroxytryptamine3 receptor antagonist, at doses of
      50 and 100 microM produced similar decreases (50% of controls) and increases
      (120% of controls) in the extracellular output of dopamine and DOPAC,
      respectively. HVA and 5-HIAA output levels were not affected by either
      concentration of MDL 72222. MDL 72222 (10 microM) produced a slight and transient
      increase in the release of dopamine and a decrease in the extracellular output of
      DOPAC. HVA and 5-HIAA extracellular output was not affected by MDL 72222 (10
      microM) perfusion. 5. Co-perfusion of MDL 72222 (10 and 100 microM) or
      tetrodotoxin (1 microM) with PBG (50 microM) did not modify the effect produced
      by PBG (50 microM) alone on the release of dopamine. 6 These results suggest that
      the effect of PBG on the release of dopamine is mainly carrier-mediated.

PMID- 8564218
TI  - Effect of diabetes on relaxations to non-adrenergic, non-cholinergic nerve
      stimulation in longitudinal muscle of the rat gastric fundus.
AB  - 1. The effect of 8-week streptozotocin-induced diabetes has been examined on
      relaxations to non-adrenergic, non-cholinergic (NANC) nerve stimulation in
      longitudinal strips of rat gastric fundus. 2. In the presence of noradrenergic
      and cholinergic blockade and raised tissue tone, electrical field stimulation
      (0.5-4 Hz, 30 s trains) induced frequency-dependent relaxations that were
      significantly smaller in gastric fundus strips from diabetic rats than in strips
      from control rats. 3. NG-nitro-L-arginine methyl ester (NAME, 100 microM)
      significantly reduced NANC relaxations in muscle strips from both control and
      diabetic rats, but the reduction was greater in muscle strips from diabetic rats
      than in those from control rats at frequencies of 2 and 4 Hz. alpha-Chymotrypsin
      (1 u ml-1) slightly reduced relaxations to nerve stimulation in muscle strips
      from both control and diabetic rats. 4. The duration of NANC nerve relaxations (1
      4 Hz, 30 s trains) was smaller in muscle strips from diabetic rats than in those
      from control rats. The duration of NANC relaxations was reduced by alpha
      chymotrypsin (1 u ml-1) in muscle strips from control rats but not in muscle
      strips from diabetic rats. 5. Relaxations to both nitric oxide (NO; 1-30 microM)
      and vasoactive intestinal polypeptide (VIP; 0.1-30 microM) were concentration
      dependent and did not differ between muscle strips from control and diabetic
      rats. 6. The results suggest that streptozotocin-induced diabetes impairs
      relaxations to NANC nerve stimulation in the rat gastric fundus, which are
      largely mediated by NO and to a lesser extent by VIP. The impairment appears to
      occur at the prejunctional level, as smooth muscle reactivity to NO and VIP is
      not altered.

PMID- 8564219
TI  - Renal effects of infusion of rilmenidine and guanabenz in conscious dogs:
      contribution of peripheral and central nervous system alpha 2-adrenoceptors.
AB  - 1. We tested the renal effects of the alpha 2-adrenoceptor agonists, rilmenidine
      and guanabenz and the antagonists, 2-methoxyidazoxan and idazoxan, in conscious
      dogs. Our aim was to test the hypothesis that putative imidazoline (I) receptors
      influence renal function. We reasoned that since rilmenidine and guanabenz are
      selective for I1- and I2-binding sites respectively, an influence of one of these
      receptive sites on renal function would be reflected in qualitative differences
      between the effects of these agents. Moreover, effects mediated by putative I
      receptors should be relatively resistant to antagonism by the selective alpha 2
      adrenoceptor antagonist, 2-methoxyidazoxan. Since the effects of these drugs on
      renal function could be mediated in the central nervous system or periphery, the
      dogs were studied under both normal and ganglion-blocked conditions. 2. In dogs
      with intact autonomic reflexes, 2-methoxyidazoxan (15 micrograms kg-1 plus 0.6
      micrograms kg-1 min-1) produced effects consistent with a generalized increase in
      sympathetic drive, including increases in mean arterial pressure and plasma renin
      activity, and a reduction in sodium excretion. In ganglion-blocked dogs, 2
      methoxyidazoxan reduced sodium excretion but had no discernible effect on
      systemic or renal haemodynamics. We conclude that an alpha 2-adrenoceptor
      mediated mechanism in the central nervous system tonically inhibits sympathetic
      drive in the conscious dog. 3. In ganglion-blocked dogs idazoxan (3-300
      micrograms kg-1) dose-dependently increased arterial pressure. This was not
      abolished by concomitant administration of 2-methoxyidazoxan (0.3-30 micrograms
      kg-1). The pressor effect of idazoxan is therefore probably mediated by an
      agonist action at alpha 1-adrenoceptors. 4. The effects of infusions of
      rilmenidine (0.1-1.0 mg kg-1) and guanabenz (10-100 micrograms kg-1) were
      indistinguishable. They comprised dose-dependent increases in mean arterial
      pressure, urine excretion, and glomerular filtration rate (the latter in ganglion
      blocked dogs only), and dose-dependent reductions in heart rate, renal blood flow
      and sodium excretion (only in dogs with intact autonomic reflexes). All of these
      effects were antagonized by 2-methoxyidazoxan. 5. We conclude that the renal
      effects of rilmenidine and guanabenz infusions in conscious dogs are
      predominantly, if not completely, attributable to activation of alpha 2
      adrenoceptors. Our results do not support the hypothesis that putative I
      receptors contribute towards the renal effects of these agents.

PMID- 8564220
TI  - The effects of formoterol on plasma exudation produced by a localized acute
      inflammatory response to bradykinin in the tracheal mucosa of rats in vivo.
AB  - 1. The effects of formoterol, a beta 2-adrenoceptor agonist, on plasma protein
      exudation and microvascular permeability induced by topical, i.e. applied onto
      the tracheal mucosal surface, bradykinin (10 nmol; 20 microM, 5 min, 0.1 ml min
      1) were studied in a perfused segment of trachea prepared in situ in
      anaesthetized rats. 2. Bradykinin increased the amount of plasma (fluorimetric
      assay for protein) in the perfusate (response; 10.98 +/- 0.357 microliters, n =
      69; total increase in plasma over basal during 45 min after start of bradykinin
      application) and 2 responses at a 90 min interval were reproducible. Carbon
      labelling was seen in tracheal sections from animals that received i.v. colloidal
      carbon, indicating that bradykinin caused tracheal microvessels to leak (increase
      in microvascular permeability). 3. Five minutes after topical formoterol, 5 or 30
      nmol (10 or 60 microM perfused for 5 min), the bradykinin response was
      significantly reduced. The effects of formoterol were not dose-related, i.e. were
      maximal at 5 nmol. The bradykinin response was at control levels 30 min after 5
      nmol formoterol. After 30 nmol formoterol, the response was still reduced 120 min
      later. The bradykinin response was significantly reduced 60 min after systemic
      formoterol (i.p., 0.029 to 870 nmol kg-1) and, for 290 nmol kg-1 i.p. formoterol,
      this reduction was shown to last at least 150 min. 4 The bradykinin response was
      not prevented by supramaximal doses of topical (30 nmol) or i.p.(870 nmol kg-1)
      formoterol and carbon-labelled microvessels were seen in tracheal sections from
      all animals that received formoterol, although these were less in number and less
      densely labelled than in the absence of formoterol. There was a correlation
      between the plasma exudation response (ul) and the number of carbon-labelled
      vessels (Spearman's correlation coefficient 0.415, P<0.001).5 In animals
      pretreated with propranolol (3 pmol kg-1, i.v.), 29 nmol kg-1 formoterol, i.p.,
      did not reduce the bradykinin response. However, propranolol itself markedly
      potentiated the bradykinin response which confounded the interpretation of its
      effects on formoterol.6 The study has shown, in a preparation of rat trachea in
      situ, that supramaximal doses of the beta2-adrenoceptor agonist, formoterol (a)
      produced a sustained, but incomplete, inhibition of plasma exudation (induced by
      topical bradykinin), and (b) did not prevent bradykinin-induced leaky
      microvessels. The data support the view that, at least in rodent airways, beta2
      adrenoceptor agonists attenuate, but do not abolish, the microvascular
      permeability effects of bradykinin, a putative asthma mediator.

PMID- 8564221
TI  - Calcium channel subtypes for the sympathetic and parasympathetic nerves of guinea
      pig atria.
AB  - 1. The Ca2+ channel subtypes of the autonomic nerves of guinea-pig atria were
      elucidated by monitoring the effects of specific Ca2+ channel blockers on the
      negative and positive inotropic responses associated respectively, with
      stimulation of the parasympathetic and sympathetic nerves. 2. In left atria paced
      at 2-4 Hz, the negative inotropic effect induced by field stimulation of
      parasympathetic nerves (in the presence of propranolol) was abolished by omega
      conotoxin MVIIC, a blocker of N-type and OPQ subfamily Ca2+ channels. omega
      Conotoxin GVIA (an N-type blocker), omega-agatoxin IVA (a P-type blocker),
      nifedipine (an L-type blocker) and Ni2+ (a T- and R-type blocker) were much less
      effective. 3. The positive inotropic response resulting from field stimulation of
      the sympathetic nerves (in the presence of atropine) was abolished by both omega
      conotoxins, while omega-agatoxin IVA, nifedipine and Ni2+ were ineffective. 4. In
      the spontaneously beating right atria, the early negative inotropic effect
      produced by 1,1-dimethyl-4-phenylpiperazinium was abolished by omega-conotoxin
      MVIIC, whereas the late positive inotropic effect was partially reduced, but not
      abolished, by a high concentration of omega-conotoxin GVIA. 5. None of the
      peptide toxins affected the chronotropic and the inotropic responses evoked by
      carbachol and isoprenaline. 6. These results suggested that, under physiological
      conditions, the release of acetylcholine from parasympathetic nerves is dominated
      by an OPQ subfamily Ca2+ channel while that of noradrenaline from sympathetic
      nerves is controlled by an N-type Ca2+ channel. Ligand-induced noradrenaline
      release appeared to recruit additional type(s) of Ca2+ channel.

PMID- 8564222
TI  - Hyperpolarization by GABAB receptor agonists in mid-brain periaqueductal gray
      neurones in vitro.
AB  - 1. The effects of GABAB receptor stimulation on membrane properties of rat
      periaqueductal gray neurones were studied by use of intracellular recordings from
      single neurones in superfused brain slices. Intracellular staining with biocytin
      was used to characterize the anatomical location of each impaled neurone. 2. The
      GABAB receptor agonist, baclofen, directly hyperpolarized or produced an outward
      current (single electrode voltage-clamp) in all 66 neurones tested. Baclofen
      induced hyperpolarizations were concentration-dependent with an EC50 of
      approximately 0.6 microM and maximum hyperpolarization with 10 microM baclofen.
      Hyperpolarizations persisted in the presence of tetrodotoxin (1 microM, n = 2).
      3. 2-OH-saclofen, a selective GABAB receptor antagonist, competitively
      antagonized baclofen-induced hyperpolarizations (n = 4) with equilibrium
      dissociation constants estimated in two neurones to be 6 and 23 microM. Naloxone
      (1 microM) did not prevent hyperpolarizations induced by baclofen (n = 34). 4.
      Hyperpolarizations induced by baclofen were associated with an increased inwardly
      rectifying potassium conductance. Ba2+ superfusion (5 to 10 mM) blocked this
      conductance increase (n = 4). Elevation of extracellular potassium concentration
      (from 2.5 to 6.5 mM) shifted the reversal potential in agreement with predictions
      of the Nernst equation. 5. Hyperpolarizations produced by baclofen (10 microM)
      desensitized (> 5% inhibition of the maximum response) in 7/22 neurones during
      continuous superfusion for 5 min. Strong desensitization (> 25% inhibition of the
      maximum response) was observed in only 2/22 neurones in the ventrolateral
      periaqueductal gray. In contrast 6/9 neurones in the laterodorsal tegmental
      nucleus displayed strong desensitization. 6. These studies demonstrate that
      baclofen acting on GABAB receptors increases potassium conductance in all lateral
      and ventrolateral periaqueductal gray neurones.

PMID- 8564223
TI  - Relaxin-induced increased coronary flow through stimulation of nitric oxide
      production.
AB  - 1. Relaxin (RLX) is a multifunctional hormone which, besides its role in
      pregnancy and parturition, has also been shown to influence the cardiovascular
      system. In this study, we investigated the effect of RLX on coronary flow of rat
      and guinea-pig hearts, isolated and perfused in a Langendorff apparatus. RLX was
      either added to the perfusion fluid at a concentration of 5 x 10(-9) M for a 20
      min perfusion, or given as a bolus into the aortic cannula at concentrations of
      10(-9) M, 5 x 10(-8) M dissolved in 1 ml of perfusion fluid. 2. RLX, given either
      for a 20-min perfusion or as a bolus in the aortic cannula to guinea-pig and rat
      isolated hearts, increased the coronary flow and the amount of nitrite, a stable
      end-product of nitric oxide (NO) metabolism, that appeared in the perfusates in a
      concentration-dependent fashion. 3. The increase in coronary flow and in nitrite
      in the perfusates induced by RLX was significantly reduced by pretreatment with
      the nitric oxide synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA, 10(
      4) M). 4. The effects of RLX on coronary flow and nitrite amounts in the
      perfusates were compared with those induced by the endothelium-dependent
      vasodilator agent, acetylcholine (ACh, 10(-8)-10(-7) M), and by the endothelium
      independent vasodilator agent, sodium nitroprusside (SNP, 10(-7)-10(-6) M). The
      results obtained show that RLX is more effective than ACh and SNP in increasing
      coronary flow. 5 The results of this study show that RLX increases coronary flow
      through stimulation of NO production; hence this hormone should be regarded as a
      novel agent capable of improving myocardial perfusion.

PMID- 8564224
TI  - A role for Q type Ca2+ channels in neurotransmission in the rat urinary bladder.
AB  - 1. In isolated bladder strips of the rat, a substantial component (46%) of the
      Ca(2+)-dependent contractile response to electrical field stimulation (5 Hz) was
      resistant to combined block of both N and P type Ca2+ channels by omega-conotoxin
      GVIA (300 nM) and omega-agatoxin-IVA (100 nM) respectively. 2. The resistant
      portion (non-N, non-P) was sensitive to omega-conotoxin-MVIIC (3 microM), which
      in addition to N and P also blocks Q type channels at this concentration. omega
      Conotoxin-MVIIC administered alone, inhibited the neurogenic response to the same
      degree as that observed in the combined presence of omega-agatoxin-IVA, omega
      conotoxin-GVIA and omega-conotoxin-MVIIC. 3. omega-Agatoxin-IVA (100 nM), a
      concentration that fully inhibits P type channels, had a negligible effect on the
      neurogenic response. Following blockade of N type Ca2+ channels with omega
      conotoxin-GVIA (300 nM), omega-agatoxin-IVA (3 microM) (a concentration well
      above that used to block P channels, inhibits Q type channels, but spares N type
      channels), inhibited the residual response to the same degree as omega-conotoxin
      MVIIC alone. 4. Results suggest that neurotransmission in rat urinary bladder is
      supported by both N and Q type Ca2+ channels.

PMID- 8564225
TI  - Factors involved in the relaxation of female pig urethra evoked by electrical
      field stimulation.
AB  - 1. Non-adrenergic, non-cholinergic (NANC) relaxations induced by electrical field
      stimulation (EFS) were studied in pig isolated urethra. The mechanism for
      relaxation was characterized by measurement of cyclic nucleotides and by study of
      involvement of different subsets of voltage-operated calcium channels (VOCCs). 2.
      EFS evoked frequency-dependent and tetrodotoxin-sensitive relaxations in the
      presence of propranolol (1 microM), phentolamine (1 microM) and scopolamine (1
      microM). At low frequencies (< 12 Hz), relaxations were rapid, whereas at high (>
      12 Hz) frequencies distinct biphasic relaxations were evoked. The latter
      consisted of a rapidly developing first phase followed by a more long-lasting
      second phase. 3. Treatment with the NO-synthesis inhibitor NG-nitro-L-arginine (L
      NOARG; 0.3 mM) inhibited relaxations at low frequencies of stimulation. At high
      frequencies (> 12 Hz) only the first relaxation phase was affected. 4.
      Measurement of cyclic nucleotides in preparations subjected to continuous nerve
      stimulation, revealed an increase in guanosine 3':5'-cyclic monophosphate (cyclic
      GMP) levels from 1.3 +/- 0.3 to 3.0 +/- 0.4 pmol mg-1 protein (P < 0.01). In the
      presence of L-NOARG, there was a significant decrease in cyclic GMP content to
      control. However, there was no increase in cyclic GMP content in response to EFS.
      Levels of cyclic AMP remained unchanged following EFS. 5. Treatment with the N
      type VOCC-inhibitor, omega-conotoxin GVIA (0.1 microM) reduced NO-dependent
      relaxations, the effect being most pronounced at low frequencies (1-4 Hz) of
      stimulation. The NO independent second phase of the relaxation, studied in the
      presence of L-NOARG (0.3 mM) at 16-30 Hz, was however markedly reduced or
      abolished by omega-conotoxin GVIA. omega-Conotoxin MVIIC (1 microM)or omega
      agatoxin IVA (30 nM) had no effect on electrically evoked relaxations.6. These
      results suggest that NANC-nerve derived urethral relaxation in the pig consists
      of two apparently independent components. One is mediated by NO and associated
      with an increase in cyclic GMP content. The other mediator is unknown and
      produces relaxations not associated with changes in levels of cyclic nucleotides.
      The release of this mediator seems to involve the N-type VOCC, since the
      relaxation was markedly reduced or abolished by omega-conotoxin GVIA.

PMID- 8564226
TI  - Alpha 1A-adrenoceptor-mediated contractile responses of the human vas deferens.
AB  - 1. The predominant alpha 1-adrenoceptor mediating contractions of the human vas
      deferens has been characterised in vitro by use of subtype selective antagonists.
      2. Responses of human epididymal vas deferens were obtained to phenylephrine in
      the presence of amine uptake inhibitors and propranolol. The effects of the alpha
      1-adrenoceptor antagonists, 5-methylurapidil, oxymetazoline, WB4101, prazosin and
      chloroethylclonidine were examined and also the L-type calcium channel blocker,
      nifedipine. 3. 5-Methylurapidil, WB4101, oxymetazoline and prazosin acted as
      competitive antagonists of the responses to phenylephrine, yielding pA2 values of
      8.8, 9.2, 7.7 and 8.8 respectively. All four antagonists produced Schild plots
      with slopes similar to unity and maximum responses to phenylephrine were not
      altered in the presence of any of the antagonists. 4. Tamsulosin (1 nM) caused
      rightward shifts of phenylephrine concentration-response curves yielding an
      apparent pKB value of 10.0. However, maximum responses were also reduced by 51%
      with this concentration of antagonist. 5. Incubation of tissues with
      chloroethylclonidine (100 microM for 40 min) failed to alter responses
      significantly but the presence of nifedipine (1 microM) reduced maximum responses
      to phenylephrine by 32%. 6. The high affinity of 5-methylurapidil, oxymetazoline
      and WB4101, together with the failure of chloroethylclonidine to antagonize
      responses, indicate that the predominant alpha 1-adrenoceptor mediating
      contraction of the human vas deferens has the characteristics previously
      described for the pharmacologically-defined alpha 1A-adrenoceptor. The data are
      also consistent with those described for the cloned alpha 1c-adrenoceptor subtype
      thereby supporting the hypothesis that the two receptors are identical. The human
      vas deferens therefore represents a readily accessible preparation for functional
      studies of the human alpha 1A-adrenoceptor.

PMID- 8564227
TI  - Selectivity of the imidazoline alpha-adrenoceptor agonists (oxymetazoline and
      cirazoline) for human cloned alpha 1-adrenoceptor subtypes.
AB  - 1. To investigate the structure-activity relationships of alpha-adrenoceptor
      agonists for the alpha 1-adrenoceptor subtypes, we have compared the imidazoline
      class of compounds, oxymetazoline and cirazoline, with the phenethylamine,
      noradrenaline, in their affinities and also in their intrinsic activities in
      Chinese hamster ovary (CHO) cells stably expressing the cloned human alpha 1
      adrenoceptor subtypes (alpha 1a-, alpha 1b-, and alpha 1d-subtypes). 2.
      Radioligand binding studies with [125I]-HEAT showed that cirazoline and
      oxymetazoline had higher affinities at alpha 1a-subtype than at alpha 1b- and
      alpha 1d-subtypes, while noradrenaline had higher affinity at the alpha 1d
      subtype than at alpha 1a- and alpha 1b-subtypes. 3. In functional studies,
      cirazoline caused transients of cytosolic Ca2+ concentrations ([Ca2+]i response)
      in a concentration-dependent manner and developed a maximal response similar to
      that to noradrenaline in CHO cells expressing the alpha 1a-subtype, while it
      acted as a partial agonist at alpha 1b- and alpha 1d-adrenoceptors.
      Oxymetazoline, on the other hand, was a weak agonist at alpha 1a-adrenoceptors,
      and has no intrinsic activity at the other subtypes. 4. Using the
      phenoxybenzamine inactivation method, the relationships between receptor
      occupancy and noradrenaline-induced [Ca2+]i response for alpha 1a- and alpha 1d
      subtypes were found to be linear, whereas it was moderately hyperbolic for the
      alpha 1b-subtype, indicating the absence of receptor reserves in CHO cells
      expressing alpha 1a- and alpha 1d-subtypes while there exists a small receptor
      reserve for CHO cells expressing the alpha 1b-subtype. 5 In summary, our data
      obtained in cells exclusively expressing a single receptor subtype support the
      idea that the relative role of agonist affinity and intrinsic activity may vary
      depending on the subtype of alphal-adrenoceptor.

PMID- 8564228
TI  - Pharmacological selectivity of the cloned human P2U-purinoceptor: potent
      activation by diadenosine tetraphosphate.
AB  - 1. The human P2U-purinoceptor was stably expressed in 1321N1 human astrocytoma
      cells and the pharmacological selectivity of the expressed receptor was studied
      by measurement of inositol lipid hydrolysis. 2. High basal levels of inositol
      phosphates occurred in P2U-purinoceptor-expressing cells. This phenomenon was
      shown to be due to release of large amounts of ATP from 1321N1 cells, and could
      be circumvented by adoption of an assay protocol that did not involve medium
      changes. 3. UTP, ATP and ATP gamma S were full and potent agonists for activation
      of phospholipase C with EC50 values of 140 nM, 230 nM, and 1.72 microM,
      respectively. 5BrUTP, 2C1ATP and 8BrATP were also full agonists although less
      potent than their natural congeners. Little or no effect was observed with the
      selective P2Y-, P2X-, and P2T-purinoceptor agonists, 2MeSATP, alpha,beta-MeATP,
      and 2MeSADP, respectively. 4. Diadenosine tetraphosphate, Ap4A, was a
      surprisingly potent agonist at the expressed P2U-purinoceptor with an EC50 (720
      nM) in the range of the most potent P2U-purinoceptor agonists. Ap4A may be a
      physiologically important activator of P2U-purinoceptors.

PMID- 8564229
TI  - The contribution of NMDA receptor activation to spinal c-Fos expression in a
      model of inflammatory pain.
AB  - 1. Intraplantar carrageenin (6 mg 150 microliters-1) evoked a high level of
      spinal c-Fos expression in the dorsal horn, of segments L4-L5 of the spinal cord,
      and an extensive peripheral oedema; both parameters were assessed 3 h after
      carrageenin. 2. Two series of experiments were performed, with the mean total
      number of Fos like-immunoreactive neurones (Fos-LI), after carrageenin, not being
      significantly different for the two series of experiments (266 +/- 17 and 332 +/-
      31 Fos-LI neurones). For both series of experiments Fos-LI neurones were
      predominantly located in the superficial and deep laminae, only 10% of the total
      number of Fos-LI neurones were located in the nucleus proprius and 10% were
      located in the ventral horn. 3. Pre-administration of the N-methyl-D-aspartate
      (NMDA) receptor antagonist, (+)-HA966 (0.5 mg kg-1 and 2.5 mg kg-1, s.c.), 30 min
      before carrageenin, did not significantly influence the total number of Fos-LI
      neurones, as compared to control carrageenin expression. 4. Pre-administration of
      the highest dose of (+)-HA966 (10 mg kg-1) significantly reduced the number of
      deep laminae Fos-LI neurones (28 +/- 3% reduction of control number of Fos-LI
      neurones after carrageenin, P < or = 0.05), without influencing the number of
      superficial Fos-LI neurones. There was a tendency towards a reduction of the
      number of Fos-LI neurones in the nucleus proprius by the highest concentration of
      pre-administered (+)-HA966, (31 +/- 8% reduction), but this effect did not reach
      significance. 5. Pre-plus post-administered (+)-HA966 (0.5 mg kg-1), 30 min
      before and again 45 min afterintraplantar carrageenin, did not significantly
      influence the total number of Fos-LI neurones, as compared to control carrageenin
      expression.6. Pre- plus post-administration of 2.5 mg kg-1 (+)-HA966
      significantly reduced the total number of Fos-LI neurones, as compared to control
      carrageenin expression. This effect was reflected by a significant reduction in
      the number of Fos-LI neurones in the nucleus proprius (36+/-7% reduction of
      control carrageenin c-Fos expression respectively, P<0.05).7. Pre-plus post
      administration of 10 mg kg-1 of (+)-HA966 significantly reduced the number of Fos
      LI neurones in the superficial laminae, nucleus proprius, deep laminae and
      ventral horn (33 +/-0.5%,55+/-6%, 40+/-4% and 51+/-4% reduction of control
      carrageenin c-Fos expression, respectively, P<0.05,for all areas).8. A single
      post-administration of (+)-HA966 (10 mg kg-1), 45 min after intraplantar
      carrageenin, did not significantly influence the number of Fos-LI neurones in the
      superficial, deep laminae or ventral horn, but significantly reduced the number
      of Fos-LI neurones in the nucleus proprius, as compared tocontrol carrageenin
      expression (39+-/8% reduction of control carrageenin c-Fos expression, P <0.05).9
      None of the concentrations of (+)-HA966 studied, irrespective of the timing of
      administration,influenced the peripheral carrageenin oedema. Our results
      illustrate a contribution of central NMDA receptor activation to carrageenin
      evoked spinal c-Fos expression. These results extend previous studies
      demonstrating the contribution of the NMDA receptor to central hyperalgesia and
      the expression of c-Fos.

PMID- 8564230
TI  - Determination of beta-adrenoceptor subtype on rat isolated ventricular myocytes
      by use of highly selective beta-antagonists.
AB  - 1. The relative proportions of beta 1- and beta 2-adrenoceptors were determined
      by radioligand binding studies in three different rat myocardial preparations:
      membranes prepared from rat ventricle (ventricular membranes), membranes prepared
      from rat isolated ventricular myocytes (myocyte membranes), and myocytes isolated
      from rat ventricle (myocytes). 2. Competition experiments using CGP 20712A or ICI
      118,551 with [125I]-iodocyanopindolol ([125I]-ICYP) revealed high- and low
      affinity binding sites in ventricular membranes. The concentration at which each
      beta-antagonist occupied 100% of its high-affinity binding sites was 300 nM for
      CGP 20712A (beta 1-adrenoceptor) and 50 nM for ICI 118,551 (beta 2-adrenoceptor).
      3. The density of high-affinity (beta 1-adrenoceptor) and low-affinity (beta 2
      adrenoceptor) binding sites for CGP 20712A was measured by a saturation
      experiment using [125I]-ICYP in the presence and absence of 300 nM CGP 20712A. In
      ventricular membranes, the proportions of high-affinity and low-affinity binding
      sites for CGP 20712A were 73% and 27%, respectively, whereas in myocyte
      membranes, the corresponding figures were 90% and 10%, respectively. The density
      of low-affinity binding sites for CGP 20712A in ventricular membranes, defined as
      [125I]-ICYP-specific binding in the presence of 300 nM CGP 20712A, was decreased
      by addition of 50 nM ICI 118,551, whereas that in myocyte membranes was not
      affected. 4. In myocytes, specific binding of [125I]-ICYP and [3H]-CGP 12177 was
      not detected by saturation experiments performed in the presence of 300 nM CGP
      20712A. 5 In myocytes, the activation of adenylate cyclase caused by beta2
      adrenoceptors was not detected in the presence of 10 nM, 100 nM or 1000 nM CGP
      20712A, which selectively antagonized beta1-adrenoceptors.Furthermore, the
      concentration-response curve for isoprenaline-stimulated cyclic AMP accumulation
      was not shifted by 10 nm or 100 nM ICI 118,551, which selectively antagonized
      beta2-adrenoceptors, but was shifted to the right by 1000 nM ICI 118,551.6 These
      results indicate that beta2-adrenoceptors are not present on rat ventricular
      myocytes and that beta2-adrenoceptor stimulation does not cause any detectable
      production of cyclic AMP. We conclude that only beta1-adrenoceptors exist on rat
      ventricular myocytes.

PMID- 8564231
TI  - Effect of trilinolein on cyclic nucleotide formation in human platelets:
      relationship with its antiplatelet effect and nitric oxide synthesis.
AB  - 1. Trilinolein, a triacylglycerol with linoleic acid as the only fatty acid
      residue in all three esterified positions of glycerol, was recently reported to
      have an inhibitory effect on adrenaline-induced platelet aggregation. In the
      present study, we found that trilinolein at concentrations ranging from 0.01 to 1
      microM increased cyclic GMP formation and decreased cyclic AMP formation in
      washed human platelets. Both NG-nitro-L-arginine methyl ester (L-NAME) and
      methylene blue attenuated the trilinolein-induced increase in cyclic GMP. 2.
      Adrenaline decreased not only the production of cyclic AMP but also that of
      cyclic GMP. Trilinolein antagonized the inhibitory effect of adrenaline on cyclic
      GMP formation, but potentiated the inhibitory effect of adrenaline on cyclic AMP
      accumulation. 3. Both trilinolein and adrenaline enhanced intracellular calcium
      but the increment of intracellular calcium induced by them was much less than
      that produced by thrombin. 4. We propose that the anti-platelet effect of
      trilinolein is mediated through an increase in cyclic GMP, and that the change in
      cyclic GMP results from stimulation of nitric oxide synthesis in platelets. 5. We
      also propose that reduction of both cyclic AMP and cyclic GMP are involved in
      adrenaline-induced platelet aggregation.

PMID- 8564232
TI  - Histamine H1 receptor occupancy in human brains after single oral doses of
      histamine H1 antagonists measured by positron emission tomography.
AB  - 1. Histamine H1 receptor occupancy in the human brain was measured in 20 healthy
      young men by positron emission tomography (PET) using [11C]-doxepin. 2. (+)
      Chlorpheniramine, a selective and classical antihistamine, occupied 76.8 +/- 4.2%
      of the averaged values of available histamine H1 receptors in the frontal cortex
      after its administration in a single oral dose of 2 mg. Intravenous
      administration of 5 mg (+)-chlorpheniramine almost completely abolished the
      binding of [11C]-doxepin to H1 receptors (H1 receptor occupancy: 98.2 +/- 1.2%).
      3. Terfenadine, a nonsedative antihistamine, occupied 17.2 +/- 14.2% of the
      available H1 receptors in the human frontal cortex after its administration in a
      single oral dose of 60 mg. 4. There was no correlation between H1 receptor
      occupancy by terfenadine and the plasma concentration of the active acid
      metabolite of terfenadine in each subject. 5. PET data on human brain were
      essentially compatible with those on H1 receptor occupancy in guinea-pig brain
      determined by in vivo binding techniques, although for the same H1 receptor
      occupancy the dose was less in human subjects than in guinea-pigs. 6. The PET
      studies demonstrated the usefulness of measuring H1 receptor occupancy with
      classical and second-generation antihistamines in human brain to estimate their
      unwanted side effects such as sedation and drowsiness quantitatively.

PMID- 8564233
TI  - A comparison of the effects of SCA40, NS 004 and NS 1619 on large conductance
      Ca(2+)-activated K+ channels in bovine tracheal smooth muscle cells in culture.
AB  - 1. The effects of imidazopyrazine derivative, SCA40, on the activity of single
      large conductance, Ca(2+)-activated K+ (BKCa) channels in inside-out and outside
      out patches from bovine tracheal smooth muscle (BTSM) cells in culture have been
      compared with those of two established BKCa channel openers, NS 004 and NS 1619.
      2. The presence of BKCa channels on inside-out patches of BTSM membranes was
      confirmed by the single channel conductance (240 pS), selectivity for K+,
      dependence of channel activity on [Ca2+]i, and sensitivity to the selective BKCa
      channel blocker, iberiotoxin. 3. NS 004 and ND 1619 (3-30 microM) induced
      concentration-related increases in open state probability of BKCa channels when
      applied to either inside-out or outside-out BTSM patches, thus confirming that
      these compounds are activators of the BKCa channel in this preparation. 4. SCA40
      (0.1-10 microM) had no effect on the activity of BKCa channels when applied to
      either inside-out or outside-out patches which subsequently responded to the
      application of NS 004 (10-20 microM). 5. It is concluded that SCA40 does not have
      a direct effect on BKCa channel activity in BTSM patches and that the previously
      reported relaxant action of SCA40 on tracheal smooth muscle is unlikely to be
      mediated by this mechanism.

PMID- 8564234
TI  - Peripheral GABAA receptor-mediated effects of sodium valproate on dural plasma
      protein extravasation to substance P and trigeminal stimulation.
AB  - 1. The GABA transaminase inhibitor and activator of glutamic acid decarboxylase,
      valproic acid is being used for the treatment of migraine. Its mechanism of
      action is unknown. We tested the effects of sodium valproate and GABAA-agonist
      muscimol on dural plasma protein ([125I]-bovine serum albumin) extravasation
      evoked by either unilateral trigeminal ganglion stimulation (0.6 mA, 5 ms, 5 Hz,
      5 min) or substance P (SP) administration (1 nmol kg-1,i.v.) in anaesthetized
      Sprague-Dawley rats. 2. Intraperitoneal (i.p.) injection of sodium valproate or
      muscimol, but not baclofen (< or = 10 mg kg-1, i.p.) dose-dependently reduced
      dural plasma protein extravasation caused either by electrical trigeminal
      stimulation (ED50: 6.6 +/- 1.4 mg kg-1, i.p., and 58 +/- 18 micrograms kg-1, i.p.
      for valproate or muscimol, respectively) or by intravenous substance P
      administration (ED50: 3.2 +/- 1.4 mg kg-1, i.p. and 385 +/- 190 micrograms kg-1,
      i.p. for valproate or muscimol, respectively). 3. Valproate (6.6 mg kg-1, i.p.)
      or muscimol (58 micrograms kg-1, i.p.) had no effect on mean arterial blood
      pressure or heart rate when measured for 30 min after i.p. administration. 4. The
      GABAA-antagonist bicuculline (0.01 mg kg-1, i.p.) completely reversed the effect
      of valproate and muscimol on plasma extravasation following electrical
      stimulation or substance P administration, whereas the GABAB-receptor antagonist,
      phaclofen (0.01-1 mg kg-1, i.p.) did not. Bicuculline or phaclofen, given alone,
      did not alter the plasma extravasation response after either electrical
      stimulation or SP administration. 5. Valproate decreased plasma extravasation
      following substance P administration in adult animals, neonatally treated with
      capsaicin by a bicuculline-reversible mechanism. This suggests that GABAA
      receptors are not found primarily on those afferent neurones or fibres which are
      sensitive to capsaicin treatment in neonatal rats.6. We conclude that sodium
      valproate blocks plasma extravasation in the meninges through GABAA mediated
      postjunctional receptors probably within the meninges. The dosages required are
      comparable to those used clinically. Agonists and modulators at the GABAA
      receptor may become useful for the development of selective therapeutic agents
      for migraine and cluster headache.

PMID- 8564235
TI  - Pharmacological profile of semotiadil fumarate, a novel calcium antagonist, in
      rat experimental angina model.
AB  - 1. The aim of the present study was to determine whether antianginal efficacy of
      semotiadil fumarate (SD-3211), a structurally novel calcium antagonist, is
      distinct from those of diltiazem, nifedipine and nisoldipine. 2. First, the
      duration of the inhibitory effects of semotiadil was compared with that of other
      Ca2+ antagonists in rat experimental angina evoked by vasopressin. Semotiadil (10
      mg kg-1, p.o.) was effective for at least 9 h in the anginal model and those
      effects of semotiadil were longer-lasting than those of diltiazem (30 mg kg-1,
      p.o.), nifedipine (10 mg kg-1, p.o.), and nisoldipine (3 mg.kg-1, p.o.). 3.
      Second, the selectivity of actions of these Ca2+ antagonists for the coronary
      arteries and myocardium was evaluated in rat isolated perfused hearts. Diltiazem
      (10(-6) M) reduced cardiac contractility without inhibiting the elevation of
      perfusion pressure evoked by acetylcholine. Semotiadil (10(-7) M) significantly
      suppressed cardiac contractility and inhibited the coronary response to
      acetylcholine. In contrast, nifedipine (3 x 10(-9)-3 x 10(-8) M) and nisoldipine
      (3 x 10(-10)-10(-8) M) did not reduce cardiac contractility at concentrations
      which significantly inhibited the increase in perfusion pressure to
      acetylcholine. 4. The selectivity of semotiadil for coronary artery and
      myocardium is intermediate between diltiazem and dihydropyridines tested in the
      present study. 5. These findings suggest that semotiadil has an advantage of
      diltiazem, nifedipine, and nisoldipine in the treatment of angina with regard to
      long-lasting action and selectivity for coronary artery and myocardium.

PMID- 8564236
TI  - Regulation of kinin-induced contraction and DNA synthesis by inflammatory
      cytokines in the smooth muscle of the rabbit aorta.
AB  - 1. In rabbit aortic rings, the contractile response to kinins is mediated by the
      B1 receptors for kinins; the response is upregulated from an initial null level
      in a time- and protein synthesis-dependent manner. Incubation (3 h) with human
      recombinant interleukin-1 beta (IL-1 beta) selectively amplified the contractile
      response to the B1 receptor agonist Sar-[D-Phe8]des-Arg9-BK, while it did not
      affect the contractile effect of other agents (angiotensin II, endothelin-1,
      phenylephrine). 2. Oncostatin M (OSM), but not macrophage migration inhibitory
      factor (MIF), increased the contractile response to the B1 receptor agonist, des
      Arg9-bradykinin (des-Arg9-BK). 3. Cultured smooth muscle cells derived from the
      rabbit aorta exhibit a significant des-Arg9-BK-induced increase in [3H]-thymidine
      incorporation if pretreated with a cyclo-oxygenase inhibitor (diclofenac) and
      concomitantly treated with the cytokines IL-1 or OSM. Angiotensin II, endothelin
      1 or phenylephrine, alone or in the presence of IL-1 beta, exerted little effect
      on DNA synthesis in these cells. 4. The pharmacological characterization of the
      mitogenic response to kinins using a set of agonist and antagonist analogues is
      consistent with mediation by B1 receptors. Des-Arg9-BK-induced DNA synthesis is
      suppressed by prostaglandin E2 by a prostacyclin mimetic (iloprost), by the
      Ser/Thr protein kinase inhibitor, H-7, and by a tyrosine kinase inhibitor (i.e.
      an erbstatin analogue). 5. B1 receptor-mediated responses and their capacity to
      be regulated by cytokines, are retained in rabbit aortic smooth muscle cells.
      Such responses could be relevant to tissue repair mechanisms and hypertrophic
      medial responses to injury in arteries.

PMID- 8564237
TI  - Accelerated desensitization of nicotinic receptor channels and its dependence on
      extracellular calcium in isolated skeletal muscles of streptozotocin-diabetic
      mice.
AB  - 1. To elucidate the influence of the diabetic state on desensitization of
      nicotinic acetylcholine (ACh) receptor channels, we investigated the time course
      of the decrease in amplitude of ACh potentials elicited by iontophoretic
      application to isolated diaphragm muscle of streptozotocin-diabetic mice. We also
      investigated time- and extracellular Ca(2+)-dependent changes in the channel
      opening frequency of ACh-activated channel currents and the involvement of
      protein kinases by use of the cell-attached patch clamp technique in single
      skeletal muscle cells. 2. When ACh potentials were evoked at 10 Hz, the decline
      in trains of ACh potentials was accelerated in the diabetic state. 3. The time
      dependent decrease in the channel opening frequency of diabetic muscle cells was
      greatly accelerated compared with normal cells in 2.5 mM Ca2+ medium. 4. This
      accelerated decrease in channel opening frequency was restored by pretreatment
      with a protein kinase C inhibitor, staurosporine (10 nM) but neither a protein
      kinase A inhibitor, H-89 (3 microM) nor a calmodulin kinase II inhibitor, KN-62
      (5 microM) were able to restore the fall in opening frequency. 5. These results
      demonstrate that in the diabetic state the desensitization of nicotinic ACh
      receptor channels may be greatly accelerated by activating protein kinase C,
      which is caused by an increase in the amount of available intracellular Ca2+.

PMID- 8564238
TI  - pH-dependent transport of procainamide in cultured renal epithelial monolayers of
      OK cells: consistent with nonionic diffusion.
AB  - 1. Previous studies suggest that procainamide is a substrate for organic
      cation/proton antiport. In order to study the coupling between procainamide flux
      and proton flux in greater detail we investigated the effects of extracellular
      procainamide addition upon intracellular pH in cultured monolayers of renal OK
      cells. Intracellular pH was monitored by use of BCECF as a probe. 2. Apical
      addition of procainamide (10 mM) caused a significant alkalinisation of
      intracellular pH. Basolateral addition of procainamide was equally effective in
      raising intracellular pH. A similar alkalinisation was found in two other renal
      cell lines: MDCK strain 1 and LLCPK1. 3. In contrast, both tetraethylammonium and
      N-methylnicotinamide, archetypal substrates for organic cation/proton antiport
      were without effect upon intracellular pH. 4. At physiological pH values,
      procainamide exists as a neutral weak base (B) and its conjugate weak acid (BH+).
      To test which species of procainamide was responsible for the alkalinisation,
      experiments in which [B] was kept constant whilst [BH+] was varied from 1.15 mM
      to 7.25 mM were performed. The results suggested that the neutral weak base (B)
      was the permeant species. 5. Procainamide efflux from procainamide-loaded cell
      monolayers resulted in a significant acidification of intracellular pH. As with
      procainamide uptake, this result could be ascribed to the movement of neutral
      weak base. 6. These effects of procainamide upon intracellular pH are consistent
      with nonionic diffusion of procainamide rather than an interaction of
      procainamide with the organic cation/proton antiporter. In addition, the results
      suggest that organic cation/proton antiport is not highly expressed in OK cells.

PMID- 8564239
TI  - Characterization of the prostanoid receptors mediating constriction and
      relaxation of human isolated uterine artery.
AB  - 1. This study was undertaken to characterize pharmacologically the prostanoid
      receptor subtypes mediating constriction and relaxation of human isolated uterine
      artery. 2. U-46619 was a potent constrictor agonist on human uterine artery (EC50
      [95% CL] = 3.5 [1.8-6.7] nM). Prostaglandin E2 (PGE2), PGF2 alpha, PGD2 and PGI2
      only weakly constricted the uterine artery, being at least 100 times less potent
      than U-46619. The PGE2 and PGI2 constrictor effects may be modified by the potent
      dilator effects of these compounds. A number of agonists which show selectivity
      for FP-, DP- and EP-receptors including ICI 81008, BW 245C, sulprostone,
      rioprostil and butaprost, failed to cause any constriction at concentrations up
      to 30 microM. 3. Constrictor responses induced by all agonists tested were
      reduced or abolished by the TP-receptor blocking drugs, GR 32191 and EP 092. pA2
      estimates for both antagonists versus U-46619 were 8.50, values which are
      consistent with their affinities at TP-receptors. 4. In preparations pre
      constricted with phenylephrine (1 microM) both PGI2 and PGE2 were potent relaxant
      agonists. The selective IP-receptor agonists, cicaprost and iloprost, also
      dilated human uterine artery and were approximately 10 fold more potent than
      PGI2. The EP2-receptor agonists, butaprost and rioprostil and the selective DP
      agonist, BW 245C, were at least 100 fold weaker than PGI2 and PGE2 suggesting
      that neither DP- nor EP2 receptors were involved. 5. We conclude that TP
      receptors mediate constriction, whereas IP- and possibly EP4-receptors mediate
      relaxation of human uterine artery.

PMID- 8564240
TI  - Effects of 8-bromoguanosine 3':5'-cyclic monophosphate on phenylephrine-induced
      phosphatidylinositol hydrolysis and contraction in rat caudal artery.
AB  - 1. The effects of 8-bromoguanosine 3':5'-cyclic monophosphate (8-bromo-cyclic
      GMP) on phenylephrine-induced contractions and phosphatidylinositol (PI)
      hydrolysis were investigated in rat isolated caudal artery. The effects of the
      nucleotide were compared to those of felodipine, a dihydropyridine Ca2+ channel
      antagonist and ryanodine, a putative depletor of intracellular Ca2+ stores. The
      purpose of this investigation was to examine the regulatory effects of cyclic GMP
      on receptor-mediated signal transduction in vascular smooth muscle. 2.
      Phenylephrine induced a concentration-dependent increase in PI hydrolysis that
      reached a maximum at 10 microM phenylephrine. Pre-incubation with felodipine (10
      nM) significantly reduced PI turnover, but did not affect basal hydrolysis.
      Similarly, removal of extracellular Ca2+ (2 mM ethylene glycol-bis(beta-amino
      ethyl ether) N, N, N', N'-tetraacetic acid (EGTA)) blocked phenylephrine-induced
      PI hydrolysis, but did not affect basal turnover. In contrast, 8-bromo-cyclic GMP
      (10 microM) did not affect phenylephrine-induced PI hydrolysis, nor did it affect
      basal turnover. 3. Phenylephrine induced concentration-dependent contractions
      that were inhibited by each of 8-bromo-cyclic GMP (10 microM), felodipine (1 nM
      and 10 nM) and ryanodine (3 microM and 10 microM). In addition, removal of Ca2+
      from the physiological salt solution (2 mM EGTA) completely abolished
      contractions elicited by phenylephrine. 4. Phenylephrine-induced contractions
      were not further affected by felodipine and 8-bromo-cyclic GMP applied
      concomitantly than by equivalent concentrations of felodipine alone. However,
      ryanodine and 8-bromo-cyclic GMP applied together significantly inhibited
      phenylephrine-induced contractions in comparison to ryanodine alone. 5 These
      results suggest that phospholipase C-activated PI hydrolysis in the rat caudal
      artery is dependent on extracellular Ca2+, mediated, in part, through
      dihydropyridine-sensitive Ca2+ channels.Inhibition of contraction by felodipine
      may be brought about through indirect inhibition of IP3 production and subsequent
      attenuation of intracellular Ca2+ release. 8-Bromo-cyclic GMP does not inhibit PI
      hydrolysis; it may regulate vascular smooth muscle contraction by inhibition of
      Ca2+ release from IP3-mediated intracellular stores, but it is unlikely that 8
      bromo-cyclic GMP affects ryanodine-sensitive stores.

PMID- 8564242
TI  - Second W.D.M. Paton Memorial Lecture. The evolution of experimental pharmacology
      as a biological science: the pioneering work of Buchheim and Schmiedeberg.

PMID- 8564241
TI  - Relationships between kallikrein secretion, kallikrein excretion and beta
      adrenoceptors in kidney cortical slices from neurogenic hypertensive dogs.
AB  - 1. Sinoaortic denervation (SAD) in dogs is characterized by an increase in blood
      pressure and heart rate as well as the development of renal morphological lesions
      similar to those observed in essential hypertension in human subjects. To assess
      the effect of SAD on the secretion of kallikrein kinin systems (KKS), we studied
      the in vitro secretion of kallikrein by renal cortical slices of normal and
      neurogenic hypertensive dogs (1 and 18 months after SAD). The method using renal
      cortical slices allowed the study of secretion of kallikrein independently of
      renal perfusion pressure. The number of renal beta-adrenoceptors was measured by
      [125I]-cyanopindolol binding. 2. SAD was associated with a marked increase in
      urinary kallikrein excretion at one month and a significant decrease at 18 months
      when compared with controls. Both changes were statistically significant (P <
      0.05). Concurrently, a progressive increase in in vitro kallikrein secretion was
      observed (+80 +/- 10% and +179 +/- 48%, 1 and 18 months after SAD, respectively).
      Moreover, the cortical slices obtained from sinoaortic denervated dogs contained
      more kallikrein than the control cortical slices (+32 +/- 16% and +55 +/- 7%, 1
      and 18 months after SAD, respectively). 3. Renal beta-adrenoceptor number
      significantly (P < 0.05) decreased 18 months after SAD from 18 +/- 2 to 8 +/- 3
      fmol mg-1 protein without any change in affinity constant. 4. Although there was
      no test of association, because the number of renal beta-adrenoceptors decreased
      whereas kallikrein secretion increased, the present data could suggest a beta
      adrenoceptor-mediated inhibition of kallikrein secretion. These results show that
      although the urinary kallikrein is decreased, the tissue secretory capacities are
      enhanced. This could suggest a renal compensatory mechanism possibly involved in
      tissue protection in dogs after SAD, although such a mechanism is not sufficient
      to reverse hypertension.

PMID- 8564243
TI  - Ramipril-induced decrease in renal lithium excretion in the rat.
AB  - 1. The interaction of ramipril, an inhibitor of angiotensin I converting enzyme,
      with renal lithium handling was analysed in conscious normotensive Wistar rats
      and compared with the known increase in renal tubular lithium reabsorption
      induced by the non-steroidal anti-inflammatory drug, indomethacin. 2. The rats
      were treated for five days with ramipril (1 mg kg-1 day-1 orally), indomethacin
      (2.5 mg kg-1 day-1 intramuscularly) or their solvents. Lithium chloride (16.7 mg
      kg-1 intraperitonealy) was given as a single dose on the fifth day and renal
      functions were measured. 3. Ramipril induced a decrease in renal lithium
      clearance which was correlated with the decrease in the quantity of filtered
      lithium and the increase in the tubular fractional reabsorption of the metal.
      Ramipril also reduced the systolic blood pressure of the rats by about 15 mmHg.
      4. In the absence of any effect on creatinine clearance or systolic blood
      pressure, indomethacin increased renal fractional lithium reabsorption and led to
      an increase in plasma lithium levels, as previously reported by our group. 5. In
      conclusions, our results indicate that ramipril decreases renal lithium excretion
      in Wistar rats, when given orally at a dose of 1 mg kg-1 day-1 over five days.

PMID- 8564244
TI  - Absence of a losartan interaction with renal lithium excretion in the rat.
AB  - 1. The interaction of losartan, a non-peptide specific AT1 receptor antagonist
      with the renal handling of lithium was analysed in conscious normotensive Wistar
      rats and compared with the known increase in renal tubular lithium reabsorption
      induced by the non-steroidal anti-inflammatory drug, indomethacin. 2. The rats
      were treated for five days with losartan (10 mg kg-1 day-1, orally), indomethacin
      (2.5 mg kg-1 day-1, intramuscularly) or their solvents. Lithium chloride (16.7 mg
      kg-1, i.p.) was given as a single dose on the fifth day; renal functions were
      then measured. 3. Indomethacin, in the absence of any effect on creatinine
      clearance, increased renal fractional lithium reabsorption and led to an increase
      in plasma lithium levels. 4. Losartan did not modify renal lithium handling and
      its plasma level. No change was observed in renal lithium clearance, the quantity
      of filtered lithium or the fractional reabsorption of the metal. As expected,
      losartan had no effect on systolic blood pressure in normotensive rats. 5. In
      conclusion, our results indicate that losartan, when given orally in the rat at a
      dose of 10 mg kg-1 day-1 over five days, does not modify renal lithium handling.
      They suggest that blockade of the angiotensin II receptors does not interfere
      with renal lithium reabsorption, which occurs mainly at a proximal tubular site.

PMID- 8564245
TI  - Demonstration of a 'septide-sensitive' inflammatory response in rat skin.
AB  - 1. Measurement of plasma protein extravasation induced by the natural tachykinins
      following intradermal administration in rat skin indicated equipotency between
      substance P (SP), neurokinin A (NKA) and neurokinin B (NKB). The selective NK1
      receptor agonist, [Sar9]SP sulphone was 10-100 times more potent than SP. The
      synthetic hexapeptide, septide, [pGlu6, Pro9]SP-(6-11), which has been proposed
      to act on a distinct NK1 receptor subtype/binding site was equipotent with
      [Sar9]SP sulphone. 2. The selective NK2 receptor agonist [beta Ala8]NKA(4-10)
      (0.1-1 nmol) and the selective NK3 receptor agonist, senktide (0.1-1 nmol) were
      both ineffective in producing oedema. The selective NK2 receptor antagonist, SR
      48, 968 (0.3 mumol kg-1) had no significant inhibitory effects upon oedema
      induced by approximately equiactive doses of SP (0.2 nmol), septide (0.002 nmol),
      [Sar9]SP sulphone (0.002 nmol), or NKB (0.3 nmol). These results together suggest
      that neither NK2 nor NK3 receptors are involved in oedema formation in rat skin.
      3. The non-peptide tachykinin NK1 receptor antagonist, RP 67,580 (1-3 mumol kg
      1), inhibited plasma protein extravasation induced by septide (0.002 nmol) to a
      greater extent than that to SP (0.2 nmol). RP 67,580 (1 mumol kg-1) produced a
      significant inhibition of approximately 66% of the response to septide (0.002
      nmol) only. Increasing the dose of RP 67,580 3 fold resulted in inhibition of the
      response to SP (0.2 nmol) and [Sar9]SP sulphone (0.002 nmol) by approximately 66%
      and 64% respectively with the response to septide being inhibited by
      approximately 70%. 4. Co-administration of the nitric oxide (NO) synthase
      inhibitor, NG-nitro-L-arginine methyl ester (L-NAME)(0.1 micromol) with the
      relevant tachykinin, resulted in a significant attenuation of the oedemaresponse
      to septide (0.1 nmol) producing only an approximate 56% inhibition of the
      response. The response to 0.2 nmol SP was unaffected whereas the response to a
      higher dose of 1 nmol was lowered byL-NAME but this did not reach significance.5.
      Degranulation of mast cells, achieved by pretreatment with compound 48/80 (5 mg
      kg-1) for 3 consecutive days, significantly inhibited the oedema responses to
      only high dose SP (1 nmol) and[Sar9SP sulphone (0.002 nmol). SP (0.2 nmol),
      septide (0.002 nmol), NKA (0.2 nmol) and NKB(0.3 nmol) were unaffected by this
      treatment.6. RP 67,580 (0.3-3 microM kg-1) inhibited oedema induced by both 0.002
      nmol and 0.1 nmol of septide.When using equiactive doses of SP only the response
      to the lower dose of 0.2 nmol SP was significantly inhibited, while RP 67,580 (3
      micromol kg1) did not affect the response to 1 nmol SP.7 These results suggest
      distinct mechanisms of action for SP and septide in producing plasma protein
      extravasation in rat skin. The response induced by septide is blocked by RP
      67,580 and is both NO dependent and mast-cell independent. In contrast the
      response to SP is only partially blocked by RP67,580 and is NO-independent. These
      data support the existence of a distinct 'septide-sensitive' receptor/binding
      site and suggest that this site is involved in tachykinin-induced oedema
      formation in rat skin.

PMID- 8564246
TI  - Central cardiovascular effects of acetylcholine in the conscious dog.
AB  - 1. The effects of central cholinomimetic drugs on cardiovascular and vasoactive
      hormonal responses (blood pressure, heart rate, catecholamines, vasopressin,
      atrial natriuretic factor, neuropeptide Y plasma levels and plasma renin
      activity) were investigated in conscious Beagle dogs. For this purpose a catheter
      was chronically implanted into each dog's cisterna magna to allow repeated
      central injections in the awake animals. 2. Intracisternal acetylcholine (20
      micrograms kg-1) significantly increased systolic and diastolic blood pressure.
      These changes were accompanied by an initial short term tachycardia followed by a
      long lasting bradycardia. Intracisternal acetylcholine also increased
      noradrenaline, adrenaline and vasopressin plasma levels, decreased plasma renin
      activity but did not modify plasma levels of neuropeptide Y and atrial
      natriuretic factor. 3. The effects of acetylcholine were completely abolished by
      pretreatment with intracisternal injection of the muscarinic antagonist, atropine
      (5 micrograms kg-1) but not by the intracisternal injection of the nicotinic
      antagonist, mecamylamine (25 micrograms kg-1). 4. The present results demonstrate
      that there are qualitative and quantitative differences between the central
      cardiovascular effects of acetylcholine in conscious dogs compared to what we
      previously reported, using a comparable protocol, in anaesthetized dogs. Under
      both conditions, we observed a central cholinergically mediated increase in blood
      pressure secondary to an increase in sympathetic tone and vasopressin release but
      these responses were shorter (less than 10 min) in the conscious dogs than in
      anaesthetized dogs (more than 10 min). Moreover, we detected in the response to
      the central cholinergic stimulation in the conscious dogs a significant increase
      in plasma adrenaline levels and biphasic changes in heart rate which were not
      described previously in the anaesthetized dog.

PMID- 8564247
TI  - Effects of U46619 on contractions to 5-HT, sumatriptan and methysergide in canine
      coronary artery and saphenous vein in vitro.
AB  - 1. The aim of this study was to investigate the mechanism of enhanced reactivity
      to 5'-hydroxytryptamine (5-HT) and sumatriptan previously observed in human
      isolated coronary arteries when active force was raised with the thromboxane A2
      mimetic, U46619. 2. Ring segments of dog isolated coronary artery and saphenous
      vein were suspended in organ baths and cumulative concentration-contraction
      curves to 5-HT, sumatriptan and methysergide were constructed in the absence and
      presence of low concentrations of U46619. 3. In both endothelium-intact and
      endothelium-denuded rings of coronary artery, precontraction with U46619 to low
      (< 10% Fmax; the contraction to a maximum depolarizing 125 mM KCl Krebs solution;
      KPSS) levels of active force had no effect on either the maximum contraction or
      sensitivity (pEC50) to 5-HT, sumatriptan and methysergide. 4. Ketanserin (1
      microM) had no effect on contractions to sumatriptan and methysergide in
      endothelium-denuded coronary artery rings, but reduced the maximum contraction to
      5-HT by approximately 90% to a value (5% Fmax) similar to that for sumatriptan
      and methylsergide. Under these conditions, U46619 precontraction had no effect on
      either pEC50 or maximum for 5-HT, sumatriptan or methysergide. 5. In rings of
      saphenous vein with endothelium and treated with ketanserin (1 microM), 5-HT and
      sumatriptan caused equal maximum responses of 65% Fmax which were approximately
      double that of methysergide (32% Fmax). The maximum responses and sensitivity to
      5-HT, sumatriptan, methysergide and noradrenaline were unaffected by
      precontraction with U46619. 6. Pretreatment of the saphenous vein with sodium
      nitroprusside (SNP; 10 microM) caused a small sustained relaxation and
      significantly depressed the maximal contraction to 5-HT without affecting
      sensitivity and abolished the contraction curve to sumatriptan and methysergide.
      When the relaxation response to SNP was reversed with U46619 (1-4 nM), the
      contraction curves to 5-HT, sumatriptan and methysergide were similar to those
      obtained prior to relaxation with SNP. In contrast, the same treatment with SNP
      had little affect on the contraction curve to noradrenaline.7 In conclusion, the
      pattern of U46619-enhanced reactivity of 5-HT, sumatriptan and methysergide in
      SNP-treated dog saphenous vein, highlights the importance of functional
      antagonism when assessing reactivity to contractile agonists in isolated blood
      vessels.

PMID- 8564248
TI  - Potent block of potassium currents in rat isolated sympathetic neurones by the
      uncharged form of amitriptyline and related tricyclic compounds.
AB  - 1. The block of K+ currents by amitriptyline and the related tricyclic compounds
      cyproheptadine and dizocilpine was studied in dissociated rat sympathetic
      neurones by whole-cell voltage-clamp recording. 2. Cyproheptadine (30 microM)
      inhibited the delayed-rectifier current (Kv) by 92% and the transient current
      (KA) by 43%. For inhibition of Kv, cyproheptaidine had a KD of 2.2 microM.
      Dizocilpine (30 microM) inhibited Kv by 26% and KA by 22%. The stereoisomers of
      dizocilpine were equally potent at blocking Kv and KA. 3. Amitriptyline, a weak
      base, was significantly more effective in blocking Kv at pH 9.4 (KD = 0.46
      microM) where the ratio of charged to uncharged drug was 50:50 compared with pH
      7.4 (KD = 11.9 microM) where the ratio was 99:1. 4. N-methylamitriptyline (10
      microM), the permanently charged analogue of amitriptyline, inhibited Kv by only
      2% whereas in the same cells amitriptyline (10 microM) inhibited Kv by 36%. 5.
      Neither amitriptyline nor N-methylamitriptyline had a detectable effect on Kv
      when added to the intracellular solution. 6. It is concluded that the uncharged
      form of amitriptyline is approximately one hundred times more potent in blocking
      Kv than the charged form. However, this does not seem to be due to uncharged
      amitriptyline having better access to an intracellular binding site.

PMID- 8564250
TI  - Sumatriptan-induced saphenous venoconstriction in the anaesthetized dog through 5
      HT1-like receptor activation.
AB  - 1. The role of vasoconstrictor 5-HT1-like receptors in the control of vascular
      reactivity in vivo has been relatively little studied, particularly with regards
      to venous function. Using an anaesthetized dog model, we have investigated the
      haemodynamic profile of the selective 5-HT1-like agonist, sumatriptan, focussing
      on the reactivity of the saphenous venous bed. The key feature of our
      experimental model was the implantation of ultrasonic crystals on the adventitial
      surface of the lateral saphenous vein to provide direct and continuous
      measurement of drug-induced changes in vein diameter. Saphenous vein pressure was
      measured simultaneously via a proximal branch. 2. Sumatriptan 1-30 micrograms kg
      1, i.v., produced pronounced dose-related reductions in saphenous vein diameter
      which reached congruent to 40% at the highest dose tested. Sumatriptan also
      produced modest increases in mean blood pressure, total peripheral resistance and
      left ventricular end diastolic pressure but had little or no effect on cardiac
      output, heart rate, cardiac contractility or saphenous venous pressure.
      Sumatriptan-induced reductions in saphenous vein diameter were strongly
      antagonized by the 5-HT1-receptor antagonist, methiothepin (0.3 mg kg-1, i.v.)
      but were unaffected by the 5-HT2 antagonist, ketanserin (0.3 mg kg-1, i.v.). 3.
      Hence, 5-HT1-like receptor stimulation in vivo can result in a powerful local
      venoconstrictor effect.

PMID- 8564249
TI  - Possible role of Na(+)-K(+)-ATPase in the regulation of human corpus cavernosum
      smooth muscle contractility by nitric oxide.
AB  - 1. This study was designed to determine the role of sodium-potassium adenosine
      triphosphatase (Na(+)-K(+)-ATPase) in the regulation of human corpus cavernosum
      smooth muscle contractility by nitric oxide (NO). In addition, we determined if
      the modulation of Na(+)-K(+)-ATPase activity by NO is dependent on the increase
      in intracellular cyclic GMP concentration. 2. The effect of NO donors, sodium
      nitroprusside (SNP) and S-nitroso-glutathione (S-NO-Glu), and a permeable cyclic
      GMP analogue, 8-bromo-cyclic GMP, on Na(+)-K(+)-ATPase activity (measured as
      ouabain-sensitive 86Rb-uptake) was studied in human cultured corpus cavernosum
      smooth muscle cells (HCCSMC). In addition, the effect of the cyclic GMP lowering
      agent, methylene blue, on NO-induced increase in Na(+)-K(+)-ATPase activity was
      studied. 3. SNP (1 microM) caused time-dependent increases in ouabain-sensitive
      Rb-uptake (33-72%) over 2-20 min in HCCSMC. The stimulation of ouabain-sensitive
      Rb-uptake by SNP was concentration-dependent (30 and 102% with 0.1 and 1 microM
      SNP, respectively). Similarly, significant increases in ouabain-sensitive Rb
      uptake were obtained with 1 and 10 microM S-NO-Glu. In contrast, incubation of
      HCCSMC with 8-bromo-cyclic GMP (100 microM) did not increase ouabain-sensitive Rb
      uptake. 4. S-NO-Glu induced-increase in intracellular cyclic GMP synthesis, but
      not the increase in ouabain-sensitive Rb-uptake, was completely inhibited by
      methylene blue in HCCSMC. 5. The Na(+)-K(+)-ATPase inhibitor, ouabain, caused a
      concentration-dependent increase in tension (0.5 to 2 fold) in tissues contracted
      with 15 mM KCl. SNP and S-NO-Glu caused a concentration-dependent relaxation
      (concentration required to cause half maximal relaxation (ED50) = 0.04 and 0.2
      microM, respectively) of HCC strips contracted with 15 mM K+. Ouabain (0.1 to 10
      microM) inhibited the response to SNP and S-NO-Glu by shifting the concentration
      response curves to the right and preventing full smooth muscle relaxation.6.
      These results indicate that the activity of Na+-K+-ATPase modulates the
      contractility of HCC smooth muscle, and that NO stimulates Na+-K+-ATPase activity
      in HCCSMC independently of its ability to increase the intracellular cyclic GMP
      concentration. They also suggest that stimulation of Na+-K+-ATPase activity plays
      an important role in NO-induced relaxation of HCC smooth muscle

PMID- 8564251
TI  - Electrical activity in rat tail artery during asynchronous activation of
      postganglionic nerve terminals by ciguatoxin-1.
AB  - 1. The effects of ciguatoxin-1 (CTX-1) on the membrane potential of smooth muscle
      cells have been examined in rat proximal tail arteries isolated in vitro. 2. CTX
      1 (> or = 10 pM) increased the frequency of spontaneous excitatory junction
      potentials (s.e.j.ps). At 100-400 pM, there was also a marked and maintained
      depolarization (19.7 +/- 1.4 mV, n = 14, at 400 pM). 3. In 20-400 pM CTX-1,
      perivascular stimuli evoked excitatory junction potentials (e.j.ps) which were
      prolonged in time course relative to control. 4. Although threshold and latency
      of the e.j.p. were not affected by CTX-1 (< or = 400 pM), propagated impulses
      were blocked at > or = 100 pM. 5. The spontaneous activity and the depolarization
      produced by CTX-1 were reduced in the presence of Ca2+ (0.1 mM)/Mg2+ (25 mM),
      omega-conotoxin (0.1 microM) or Cd2+ (50-100 microM). 6. All effects of CTX-1
      were abolished by tetrodotoxin (0.3 microM). 7. Raised Ca2+ (6 mM) reduced the
      depolarization and spontaneous activity produced by CTX-1. 8. In 400 pM CTX-1,
      the membrane repolarized (17 +/- 3.2 mV, n = 4) following the addition of
      phentolamine (1 microM). S.e.j.ps and e.j.ps were selectively abolished by
      suramin (1 mM), and the membrane repolarized by 1.3 +/- 1.6 mV (n = 4). 9. We
      conclude that CTX-1 releases noradrenaline and ATP by initiating asynchronous
      discharge of postganglionic perivascular axons. In 100-400 pM CTX-1, the smooth
      muscle was depolarized to levels resembling those recorded in this artery during
      ongoing vasoconstrictor discharge in vivo.

PMID- 8564252
TI  - The roles of spinal adenosine receptors in the control of acute and more
      persistent nociceptive responses of dorsal horn neurones in the anaesthetized
      rat.
AB  - 1. We describe here the effects of intrathecal selective adenosine receptor
      agonists on acute and more persistent evoked responses of dorsal horn nociceptive
      neurones recorded in intact rats anaesthetized with halothane. 2. The effects of
      the A1 receptor agonist, N6-cyclopentyladenosine and the non-selective agonist 2
      chloroadenosine as well as the A2a receptor agonist, 2-p-(2-carboxyethyl)
      phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride were gauged on the C
      , A delta-, A beta-fibre, post-discharge and wind-up responses produced by
      peripheral tanscutaneous stimulation. The antagonists, theophylline and 8(p
      sulphophenyl) theophylline were also tested alone and to reverse the agonist
      effects. 3. Subcutaneous formalin (5%) was used to produce a more prolonged
      nociceptive response initiated by peripheral inflammation. 4. Both N6
      cyclopentyladenosine and 2-chloroadenosine produced inhibitions of the C-fibre
      evoked responses, wind-up and post-discharge of the neurones with no significant
      effects on the A beta responses. By contrast, the A delta evoked responses were
      facilitated over the same time course and dose-range as the inhibitions. N6
      cyclopentyladenosine was more potent and effective than 2-chloroadenosine. In
      marked contrast to these agonists, the A2a agonist produced only weak non
      specific inhibitions. Theophylline and 8(p-sulphophenyl) theophylline alone had
      no effect on the acute responses but prevented or reversed inhibitory effects of
      N6-cyclopentyladenosine. 5. The formalin response was markedly inhibited by
      spinal N6-cyclopentyladenosine with both the acute first phase and more prolonged
      second phase being dose-dependently inhibited. N6-cyclopentyladenosine was
      considerably more potent on the formalin response than on the other neuronal
      measures. 6 The results suggest a role of adenosine Al receptors in the
      modulation of both acute and inflammatory nociception in the spinal cord.

PMID- 8564253
TI  - Lack of involvement of bradykinin in the vascular sympathoinhibitory effects of
      angiotensin converting enzyme inhibitors in spontaneously hypertensive rats.
AB  - 1. The aim of this study was to investigate the contribution of endogenous
      bradykinin to the vascular sympathoinhibitory effects exerted by angiotensin I
      converting enzyme inhibitors (ACEIs) in the spontaneously hypertensive rat (SHR).
      2. Adult SHRs were treated daily for 8 days with either perindopril (3 mg kg-1),
      or a selective angiotensin II AT1 receptor antagonist, losartan (10 mg kg-1) both
      given orally--these two doses being equipotent in inhibiting angiotensin I (AI)
      induced vascular responses--or distilled water (controls). After pithing, the
      animals were instrumented for determination of blood pressure, heart rate,
      cardiac output, regional (renal, mesenteric, hindlimb) blood flows (pulsed
      Doppler technique) and corresponding vascular resistances. Afterwards, half of
      the animals of each group were given the selective bradykinin B2 receptor
      antagonist, icatibant, used in a dose (10 micrograms kg-1, i.v.) that achieved B2
      receptor blockade, the other half received saline (10 microliters kg-1, i.v.).
      Haemodynamic responses to increasing frequencies of spinal cord stimulation were
      then measured. 3. Pressor and vasoconstrictor responses to AI were significantly
      and similarly reduced in both perindopril- and losartan-treated groups.
      Perindopril and losartan both decreased to a similar extent the pressor and
      vasoconstrictor responses to electrical stimulation of the spinal cord. 4. In the
      dose used, icatibant did not affect any of the investigated haemodynamic
      parameters in any of the experimental groups. Furthermore, icatibant did not
      affect the stimulation frequency-response curves in the control animals and did
      not modify the vascular sympathoinhibitory effects exerted by perindopril and by
      losartan. 5 Taken together, these results demonstrate that endogenous bradykinin
      does not, through B2 receptor activation, contribute to the vascular
      sympathoinhibitory effects of ACEIs in SHRs.

PMID- 8564254
TI  - Haemodynamic effects of losartan and the endothelin antagonist, SB 209670, in
      conscious, transgenic ((mRen-2)27), hypertensive rats.
AB  - 1. Hypertensive transgenic (TGR(mRen-2)27) (abbreviated to TG) rats (n = 6) and
      their normotensive Sprague-Dawley (SD) control strain (n = 7) were chronically
      instrumented for the measurement of cardiac haemodynamics. The hypertension in TG
      rats (mean blood pressure 181 +/- 9 mmHg) was entirely attributable to a
      reduction in total peripheral conductance (TG rats = 169 +/- 7, SD rats = 292 +/-
      15 microliters min-1 mmHg-1 100g-1) since cardiac index was not different in the
      two strains (TG rats = 30.5 +/- 1.2, SD rats = 29.5 +/- 1.6 ml min-1 100g-1). 2.
      In other animals instrumented for the assessment of regional haemodynamics, the
      extent of peripheral vasoconstriction was similar in renal, mesenteric and
      hindquarters vascular beds in the TG rats (reduction in vascular conductance
      relative to SD rats = 42%, 46% and 49%, respectively). 3. During an 8 h
      observation period with saline infusion, or following injection of losartan (10
      mg kg-1) in SD rats there was no hypotension or regional vasodilation. With
      infusion of the endothelin antagonist, SB 209670 (10 micrograms kg-1 min-1),
      there was a slight hypotension, but no significant vasodilation; co
      administration of losartan and SB 209670 caused a similar profile of effect,
      although the hypotension was increased. 4. With the same experimental protocol in
      TG rats, losartan caused a biphasic, progressive fall in mean arterial blood
      pressure accompanied by renal, mesenteric and hindquarters vasodilation. Although
      the response to SB 209670 was not biphasic, its hypotensive and vasodilator
      effects were not different from those of losartan after 8 h. In the combined
      presence of losartan and SB 209670, mean arterial blood pressure (116 +/- 5 mmHg)
      was significantly lower than with SB 209670 (132+/-4 mmHg) or losartan(136 +/- 6
      mmHg) alone, and renal, mesenteric and hindquarters vascular conductances (61 +/-
      3, 90+/-14 and 52+/-4 [kHz nmHg-1]103, respectively) were higher than the
      corresponding values following either SB 209670 (49 +/- 4, 52 +/- 4 and 34 +/- 3
      [kHz mmHg- 1]103, respectively) or losartan (43 +/- 5, 59 +/- 13 and 35+/-4 [kHz
      mmHg-1]103, respectively) alone. These results indicate the maintenance of
      hypertension inTG rats is dependent upon renal, mesenteric and hindquarters
      vasoconstriction, mediated by angiotensinII (AII) and endothelin (ET). Since we
      found that plasma ET-1 levels in TG rats (12.06+/-2.87 pmol 1-1)were lower than
      in SD rats (21.53 +/- 3.94 pmol 1-1), then it is possible that locally-generated,
      rather than circulating ET-l contributes to the widespread vasoconstriction in TG
      rats.

PMID- 8564255
TI  - Characterization of neuropeptide Y (NPY) receptors in human cerebral arteries
      with selective agonists and the new Y1 antagonist BIBP 3226.
AB  - 1. We have characterized pharmacologically the receptor subtype(s) responsible
      for the neuropeptide Y (NPY)-induced vasoconstriction in human cerebral arteries.
      NPY, PYY and several of their derivatives with well defined affinities at the
      known Y1 and Y2 receptor subtypes were used. Moreover, we tested the ability of
      the new Y1 receptor antagonist, BIBP 3226, to antagonize the NPY-induced cerebral
      vasoconstriction. 2. NPY, PYY and their agonists with high affinities at the Y1
      receptor subtype ([Leu31-Pro34]-NPY and [Leu31-Pro34]-PYY) elicited strong, long
      lasting and concentration-dependent contractions of human cerebral arteries.
      Compounds with Y2 affinity such as PYY3-36 or NPY13-36 either elicited a
      submaximal contraction at high concentrations or failed to induce any significant
      vasomotor response. Also, the application of NPY or the specific Y1 agonist,
      [Leu31-Pro34]-NPY, to human cerebral vessels pretreated with the Y1 agonist,
      NPY13-36, resulted in contractile responses identical to those obtained when
      these compounds were tested without prior application of NPY13-36. 3. The order
      of agonist potency at the human cerebrovascular receptor was: [Leu31-Pro34]-NPY =
      [Leu31-Pro34]-PYY > or = NPY > PYY > PYY3-36 > > > NPY13-36, which corresponded
      to that reported previously at the neuronal and vascular Y1 receptors. 4.
      Increasing concentrations (10(-9)-10(-6) M) of the Y1 receptor antagonist, BIBP
      3226, to human cerebral vessels caused a parallel and rightward shift in the NPY
      dose-response curves without any significant change in the maximal contractile
      response. The calculated pA2 was 8.52 +/- 0.13, a value compatible with the
      reported affinity at the rodent and human Y1 receptor. 5. We conclude that Y1
      receptors exclusively, mediate the NPY-induced contraction in human cerebral
      arteries and we show that BIBP 3226 is a potent and competitive antagonist of
      this YI-mediated vasoconstriction.

PMID- 8564256
TI  - Effect of interleukin-4 and interleukin-10 on leucocyte migration and nitric
      oxide production in the mouse.
AB  - 1. The effect of systemic treatment of mice with murine recombinant interleukin-4
      (IL-4) or interleukin-10 (IL-10) on neutrophil infiltration into a specific
      tissue site and nitric oxide (NO) production from peritoneal macrophages was
      investigated. 2. Intravenously (i.v.) administered IL-4 (0.01-10 micrograms per
      mouse, approximately 0.3-300 micrograms kg-1, i.v.) and IL-10 (0.01-1 micrograms
      per mouse, approximately 0.3-30 micrograms kg-1, i.v.) dose-dependently inhibited
      neutrophil accumulation into a 6-day-old murine air-pouch induced by local
      application of interleukin-1 beta (IL-1 beta, 5 ng), with approximate ED50s of
      0.35 and 0.90 micrograms, respectively. Neither IL-4 (1 micrograms, 30 micrograms
      kg-1, i.v.) nor IL-10 (1 micrograms, 30 micrograms kg-1, i.v.) prevented
      leucocyte accumulation in the mouse air-pouches when interleukin-8 (IL-8, 1
      micrograms) was used as chemoattractant. Similarly, neither cytokine had any
      effect on the in vitro up-regulation of CD11b antigen on the surface of murine
      circulating neutrophils. 3. Treatment of mice with lipopolysaccharide (LPS, 0.3
      mg kg-1, i.p.) caused an increase in the formation of NO (measured as nitrite
      accumulation) in the supernatant of peritoneal macrophages ex vivo. Pretreatment
      of mice with IL-4 (0.01-1 micrograms i.v., 20 min before LPS), but not with IL-10
      (1 micrograms i.v., 20 min before LPS), caused a dose-dependent reduction in this
      LPS-stimulated formation of nitrite by peritoneal macrophages ex vivo. 4.
      Activation of murine macrophages with LPS (1 microgram ml-1 for 24 h) in vitro
      caused a significant increase in nitrite release in the supernatant of these
      cells. Pretreatment of either J774.2 or peritoneal macrophages with IL-4 (0.1-1
      microg ml-1, 20 min before LPS), but not with IL-1O (1 microg ml', 20 min before
      LPS) caused a concentration-related attenuation of this LPS-stimulated nitrite
      formation.5 Thus, both IL-4 and IL-10 inhibit the migration of leucocytes
      (stimulated by IL-1beta>) in vivo; IL-4 (but not IL-10) inhibits the induction of
      NO synthase caused by LPS in murine macrophages in vitro and ex vivo.

PMID- 8564257
TI  - Pituitary adenylate cyclase-activating polypeptide, helospectin, and vasoactive
      intestinal polypeptide in human corpus cavernosum.
AB  - 1. The distribution and effects of pituitary adenylate cyclase-activating
      polypeptide (PACAP-27 and -38), helospectin (Hel-1 and Hel-2), and vasoactive
      intestinal polypeptide (VIP), were investigated in isolated preparations of human
      corpus cavernosum (CC). 2. Immunohistochemistry revealed coinciding profiles of
      nerve structures that showed immunoreactivities for VIP and PACAP, and VIP and
      Hel. Confocal microscopy showed the co-existence of VIP- and PACAP
      immunoreactivities, and VIP- and Hel-immunoreactivities in most (90%) varicose
      nerve structures. 3. As determined by radioimmunoassay, the amounts of VIP, PACAP
      27, and PACAP-38 in the preparations were 61.7 +/- 11.6, 0.1 +/- 0.05, and 3.7 +/
      0.5 pmol g-1 wet weight of tissue (pmol g-1 wet wt.), respectively. In tissue
      from patients with diabetes, the content of VIP was lower (13.7 +/- 0.5 pmol g-1
      wet wt.), whereas that of PACAP (-27 and -38) was unchanged. 4. Cyclic nucleotide
      levels were determined in preparations exposed to PACAP-27, PACAP-38, Hel-1, Hel
      2, and VIP. All the peptides, but Hel-2, significantly increased the
      concentrations of cyclic AMP, whereas the levels of cyclic GMP were unchanged. 5.
      The peptides concentration-dependently relaxed noradrenaline-contracted
      preparations. The order of potency was VIP > PACAP 27 > Hel-1 > Hel-2 > PACAP-38.
      6. Hel-1, VIP and PACAP-27 effectively counteracted electrically induced
      contractions. At 10(-6) M, the highest peptide concentration used, the inhibitory
      effects obtained reached 96 +/- 3%, 87 +/- 6%, and 80 +/- 3%, respectively. 7.
      The results suggest that PACAP and Hel-1 are co-localized with VIP in nerve
      structures within the human cavernous tissue, and that the peptides are effective
      relaxants of CC preparations in vitro. The role of the investigated peptides for
      penile erection remains to be established.

PMID- 8564258
TI  - Stimulation by endothelin-1 of mitogen-activated protein kinases and DNA
      synthesis in bovine tracheal smooth muscle cells.
AB  - 1. In cultures of bovine tracheal smooth muscle cells, platelet-derived growth
      factor-BB (PDGF), bradykinin (BK) and endothelin-1 (ET-1) stimulated the tyrosine
      phosphorylation and activation of both pp42 and pp44 kDa forms of mitogen
      activated protein (MAP) kinase. 2. Both ET-1 and PDGF stimulated a sustained
      activation of MAP kinase whilst the response to BK was transient. 3. Activation
      of MAP kinase occurred in a concentration-dependent manner (EC50 values: ET-1,
      2.3 +/- 1.3 nM; BK, 8.7 +/- 4.1 nM, PDGF, 9.7 +/- 3.2 ng ml-1). 4. Pretreatment
      with the protein kinase C (PKC) inhibitor Ro-318220, significantly reduced ET-1
      activation of MAP kinase at 2 and 5 min but enhanced MAP kinase activation at 60
      min. 5. Following chronic phorbol ester pretreatment, BK-stimulated activation of
      MAP kinase was abolished whilst the responses to PDGF and ET-1 were only partly
      reduced (80 and 45% inhibition respectively). 6. Pretreatment with pertussis
      toxin reduced ET-1 stimulated activation of MAP kinase particularly at later
      times (60 min), but left the responses to both PDGF and BK unaffected. 7. ET-1
      also stimulated a 3 fold increase in [3H]-thymidine incorporation which was
      abolished by pertussis toxin pretreatment. In contrast, PDGF stimulated a 131
      fold increase in [3H]-thymidine incorporation which was not affected by pertussis
      toxin. 8. These results suggest that a pertussis toxin-sensitive activation of
      MAP kinase may play an important role in ET-1-stimulated DNA synthesis but that
      activation of MAP kinase alone is not sufficient to induce the magnitude of DNA
      synthesis observed in response to PDGF.

PMID- 8564259
TI  - Mediation by CCKB receptors of the CCK-evoked hyperaemia in rat gastric mucosa.
AB  - 1. Cholecystokinin octapeptide (CCK-8) and gastrin-17 augment gastric mucosal
      blood flow in the rat. The present study examined whether the gastric vasodilator
      effect of these peptides is mediated by CCKA or CCKB receptors. 2. Intravenous
      injection of CAM-1481 (1 mg kg-1), a dipeptoid antagonist of CCKA receptors, or
      CAM-1028, a dipeptoid CCKB receptor antagonist (1 mg kg-1), had no effect on
      basal gastric mucosal blood flow as determined by the clearance of hydrogen in
      urethane-anaesthetized rats. 3. Intravenous infusion of CCK-8 or gastrin-17 (8
      200 pmol min-1) increased gastric mucosal blood flow in a dose-dependent fashion.
      The CCKB receptor antagonist, CAM-1028, significantly attenuated the hyperaemic
      response to CCK-8 and gastrin-17 whereas the CCKA receptor antagonist, CAM-1481,
      did not antagonize CCK-8 but caused a slight attenuation of the vasodilator
      response to gastrin-17. 4. The selectivity of the two antagonists was proved by
      the findings that CAM-1028, but not CAM-1481, inhibited gastric acid secretion
      evoked by CCK-8 or gastrin-17 (CCKB receptor assay) while CAM-1481, but not CAM
      1028, inhibited the CCK-8-induced contraction of guinea-pig isolated gall bladder
      strips (CCKA receptor assay). 5. These data show that the actions of CCK-8 and
      gastrin-17 to increase mucosal blood flow in the rat stomach are primarily
      mediated by CCKB receptors.

PMID- 8564260
TI  - Characterization of the functional muscarinic receptors in the rat urinary
      bladder.
AB  - 1. Muscarinic receptors mediating contraction of the rat urinary bladder were
      characterized functionally in vitro by use of atropine, 4-diphenylacetoxy-N
      methylpiperidine methiodide (4-DAMP methiodide), 4-diphenylacetoxy-N-(2
      chloroethyl)-piperidine hydrochloride (4-DAMP mustard), hexahydro-sila-diphenidol
      hydrochloride (HHSiD), the p-fluoro analogue of hexahydro-sila-diphenidol
      hydrochloride (p-F-HHSiD), methoctramine, and pirenzepine. 2. (+)-cis-Dioxolane
      contracted bladder strips in a concentration-dependent manner with an EC50 of
      0.169 +/- 0.018 microM and an Emax of 7.84 +/- 0.67 g. 3. Concentration-effect
      curves to (+)-cis-dioxolane were shifted to the right in the presence of the
      antagonists in a concentration-dependent manner. The rank order of antagonist
      affinities against the (+)-cis-dioxolane response was (pA2 values in the
      parentheses) atropine (9.28) > or = 4-DAMP methiodide (9.04) > HHSiD (8.01) > p-F
      HHSiD (7.28) = pirenzepine (7.12) > or = methoctramine (6.77, 7.25). The profile
      resembles that associated with the M3 receptor subtype. 4. Atropine, 4-DAMP
      methiodide, pirenzepine, and methoctramine had no effects on the contractile
      response to 120 mM KCl. However, HHSiD and p-F-HHSiD decreased the response to
      KCl, and 4-DAMP mustard increased it. 5. Contractile responses to electrical
      field stimulation (1-32 Hz, 0.05 ms pulse duration) were biphasic in nature. The
      tonic response was suppressed more than the phasic response by all antagonists
      except methoctramine. The suppression was not always concentration-dependent, and
      did not seem to be related to antagonism of any one receptor subtype. 6. Our
      findings are consistent with the minority M3 receptors mediating the contractile
      response to muscarinic stimulation by (+)-cis-dioxolane in the rat bladder.

PMID- 8564261
TI  - Induction of nitric oxide synthase and microvascular injury in the rat jejunum
      provoked by indomethacin.
AB  - 1. The role of nitric oxide (NO) formed by the inducible isoform of NO synthase
      (NOS) in the generation of indomethacin-induced intestinal microvascular leakage
      was investigated in the rat. 2. Indomethacin (10 mg kg-1, s.c.) provoked an
      elevation of vascular leakage of radiolabelled human serum albumin in the jejunum
      over 48 h, commencing 18 h after its administration. This was associated with the
      induction of a calcium-independent NOS, as assessed by the conversion of
      radiolabelled L-arginine to citrulline. 3. Pretreatment with the glucocorticoid,
      dexamethasone (1 mg kg-1 day-1, s.c.) inhibited the induction of NOS and reduced
      jejunal microvascular leakage, determined 24 and 48 h after indomethacin. 4.
      Administration of the broad-spectrum antibiotic, ampicillin (800 mg kg-1 day-1,
      p.o.) likewise inhibited both the induction of NOS and the plasma leakage
      observed 24 and 48 h after indomethacin. 5. Ampicillin pretreatment did not,
      however, inhibit the induction of NOS, determined 5 h following endotoxin (3 mg
      kg-1 i.v.) challenge. Furthermore, incubation with ampicillin (1 mM, 10 min) did
      not inhibit the activity of the calcium-independent isoform in vitro. 6.
      Administration of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 2
      10 mg kg-1, s.c.), at the time of the detectable expression of the inducible NOS
      (18 h after indomethacin), dose-dependently attenuated the plasma leakage,
      determined 6 later. This effect was reversed by pretreatment with L-arginine (300
      mg kg-1, s.c.) 15 min before L-NAME. 7. These findings suggest that induction of
      a calcium-independent NOS following indomethacin administration involves gut
      bacteria and leads to microvascular injury in the rat jejunum.

PMID- 8564262
TI  - Effects of 5-HT and 5-HT1A receptor agonists and antagonists on dorsal vagal
      preganglionic neurones in anaesthetized rats: an ionophoretic study.
AB  - 1. Effects of ionophoretic administration of 5-hydroxytryptamine (5-HT) and
      selective 5-HT1A receptor agonists and antagonists on identified dorsal vagal
      preganglionic and dorsal raphe neurones were studied in pentobarbitone sodium or
      chloral hydrate-anaesthetized rats, respectively. 2. Extracellular recordings
      were made from 176 preganglionic neurones in the dorsal vagal nucleus (DVN).
      Application of 5-HT at low currents (< or = 10 nA) increased the activity of
      these neurones. However, at increased currents (10-60 nA), it had a predominantly
      depressant effect. Application of selective 5-HT1A receptor antagonists, (+/-)
      pindolol or WAY-100635, attenuated the excitatory responses evoked by 5-HT. 3.
      Ionophoresis of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) (5-30 nA) increased the firing rate of 19 and
      decreased that of 67 of the 104 vagal neurones tested. Other 5-HT1A receptor
      agonists, flesinoxan and N,N-di-n-propyl-5-carboxamidotryptamine (DP-5-CT) also
      had predominantly depressant effects. 4. (+/-)-Pindolol attenuated excitations
      but not inhibitions evoked by 8-OH-DPAT. Surprisingly, WAY-100635 and 8-OH-DPAT
      produced the same effect on these neurones and when applied together, WAY-100635
      failed to attenuate the 8-OH-DPAT responses. 5. Dorsal raphe neurones were
      identified by their low, regular firing rate and their subsequent histological
      localization. 8-OH-DPAT reversibly reduced the activity in all 7 neurones tested
      and this was antagonized by WAY-100635 in all 3 neurones tested. 6. In
      conclusion, 5-HT applied to vagal preganglionic neurones evokes excitatory and
      inhibitory responses. The excitatory, but not the inhibitory responses may be
      mediated, at least in part, by activation of 5-HT1A receptors.

PMID- 8564263
TI  - The effect of a synthetic 7-thiaprostaglandin E1 derivative, TEI-6122, on
      monocyte chemoattractant protein-1 induced chemotaxis in THP-1 cells.
AB  - 1 The ability of various prostaglandins (PGs) to inhibit monocyte chemotaxis
      induced by monocyte chemoattractant protein-1 (MCP-1) was investigated with a
      human monocytic leukaemia cell line, THP-1. Moreover, to investigate the
      mechanism of the inhibitory action of PGs the involvement of either intracellular
      adenosine 3': 5'-cyclic monosphosphate (cyclic AMP) accumulation or intracellular
      Ca2+ mobilization was studied. 2 TEI-6122, a synthetic 7-thia-PGE1 derivative,
      inhibited chemotaxis of THP-1 cells induced by MCP-1 with an IC50 of 1.5 pM. Its
      inhibitory activity was 1000 fold more than that of PGE1 and PGE2 (IC50 = 2.8 nM
      and 0.9 nM, respectively), which were more potent than other PGs such as PGA1,
      PGA2, PGF2 alpha and PGI2 (IC50 > or = 1 microM). 3 With respect to the effect on
      intracellular cyclic AMP accumulation in THP-1 cells, TEI-6122 was as potent as
      PGE1 and PGE2, which were approximately 100 to 1000 fold more potent than the
      other PGs such as PGA1, PGA2 and PGI2. The minimum concentration of TEI-6122
      required to increase intracellular cyclic AMP accumulation in THP-1 cells was 1
      nM. 4 TEI-6122 and PGE1 (4 microM) transiently increased intracellular calcium
      levels in THP-1 cells. When added prior to MCP-1, both PGs partially suppressed
      the increased in Ca2+ caused by this cytokine. There were no significant
      differences between the activity of TEI-6122 and PGE1 in either respect. 5 It is
      concluded that TEI-6122, a synthetic 7-thia-PGE1 derivative is a much more potent
      inhibitor of MCP-1-induced THP-1 cell chemotaxis than PGEI and PGE2 which are the
      best inhibitors among the natural PGs tested, while neither intracellular cyclic
      AMP accumulation nor effects on Ca2+ mobilization account for the extremely
      potent inhibitory activity of TEI-6122. Thus, either a novel PGE2 receptor
      (EPreceptor) or a novel intracellular signal transduction system may be involved
      in the extremely potent chemotaxis inhibitory activity of TEI-6122.

PMID- 8564264
TI  - SMS 201-995-induced stimulation of gastric acid secretion via the dorsal vagal
      complex and inhibition via the hypothalamus in anaesthetized rats.
AB  - 1. SMS 201-995, a somatostatin analogue which interacts with highest affinities
      at somatostatin receptor subtypes 5 > 2 > or = 3, was microinjected into
      selective brain sites and its influence on pentagastrin (10 micrograms kg-1 h-1,
      i.v.)-stimulated gastric acid secretion was investigated in rats anaesthetized
      with urethane. Gastric acid secretion was measured by flushing the stomach with
      saline through a gastric cannula every 10 min. 2. SMS 201-995 microinjected into
      the dorsal vagal complex (DVC, 7, 15, 30 and 60 ng) dose-dependently increased
      pentagastrin-stimulated gastric acid secretion. The peak acid response was
      reached within 20 min and returned to basal level 50 min post-injection. SMA 201
      995 (30 ng) microinjected into the surrounding area or the central amygdala did
      not modify pentagastrin-stimulated acid secretion. 3. SMS 201-995 injected into
      the lateral ventricle (i.c.v., 100, 200, or 300 ng), paraventricular nucleus
      (PVN) or lateral hypothalamus (LH) (7.5, 15, or 30 ng) dose-dependently inhibited
      pentagastrin-stimulated gastric acid secretion. SMS 201-995 (30 ng) microinjected
      into the area surrounding the PVN or LH did not modify the acid secretion
      response to pentagastrin. 4. Vagotomy prevented the effects of SMS 201-995 (30
      ng) microinjected into the DVC and LH. 5. Spinal cord transection abolished the
      inhibitory action of SMS 201-995 (30 ng) microinjected into the PVN but not the
      LH. 6. These results demonstrate that SMS 201-995 acts in the DVC to enhance and
      in the LH and PVN to inhibit pentagastrin-stimulated gastric acid secretion. The
      action is mediated through vagal (DVC, LH)or spinal (PVN) pathways. The site
      specific pattern of acid responses to SMS 201-995 may be linked to the
      distribution of receptor subtypes at these sites that convey the different
      biological actions of somatostatin.

PMID- 8564265
TI  - Inhibition by halothane of potassium-stimulated acetylcholine release from rat
      cortical slices.
AB  - 1. Cholinergic neurones in the basal forebrain are linked to cortical activation
      and arousal. 2. The present study was designed to examine the hypothesis that
      clinically relevant doses of halothane (0.1 to 5%) would significantly reduce
      depolarization-evoked acetylcholine (ACh) release from rat cortical slices. 3.
      ACh release was measured from rat cortical slices by a chemiluminescent
      technique. 4. Depolarization-evoked ACh release was inhibited significantly by
      halothane with an IC50 of 0.38%. This value equates to 0.3 MAC (the minimum
      alveolar concentration at which no movement occurs to a standard surgical
      stimulus in 50% of subjects) for the rat. 5. The potent effect of halothane on
      ACh release suggests that this mechanism may be a target for the action of
      volatile anaesthetic agents. This in vitro effect on ACh release is consistent
      with effects of halothane reported in vivo.

PMID- 8564266
TI  - Evaluation of the receptor selectivity of the H3 receptor antagonists,
      iodophenpropit and thioperamide: an interaction with the 5-HT3 receptor revealed.
AB  - 1. In the present study we evaluated the receptor selectivity of the potent
      histamine H3 receptor antagonist, iodophenpropit (IPP) in comparison with the
      prototype antagonist, thioperamide. 2. IPP proved to be a potent competitive H3
      receptor antagonist as measured against (R)-alpha-methylhistamine-induced
      inhibition of electrically-evoked contractions of the guinea-pig jejunum (pA2 =
      9.12 +/- 0.06, Schild slope: 1.0 +/- 0.1, n = 8). In the same assay, thioperamide
      was slightly less potent (pA2 = 8.9 +/- 0.2). 3. In radioligand binding studies,
      IPP showed a high affinity for the H3 receptor. Displacement of [125I]-IPP
      binding to rat cortex membranes by unlabelled IPP resulted in a Ki value of 0.97
      +/- 0.06 nM (n = 3). In contrast, IPP showed only a weak affinity for the
      histamine H1- and H2 receptor. Displacement of [3H]-mepyramine and [125I]
      iodoaminopotentidine binding to respectively guinea-pig H1- and human H2
      receptors by IPP resulted in Ki values of 1.71 +/- 0.32 microM (n = 3) and 2.28
      +/- 0.81 microM (n = 3). For thioperamide the affinities for the H1-, H2- and H3
      receptor were respectively > 10 microM, > 10 microM and 4.3 +/- 1.6 nM (n = 7).
      4. Testing IPP and thioperamide in 39 different receptor binding assays revealed
      that IPP showed relatively high affinity for the 5-hydroxytryptamine 5-HT3
      receptor (Ki = 11 +/- 1 nM, n = 3), the alpha 2-adrenoceptor (Ki = 120 +/- 5 nM,
      n = 3) and the sigma receptor (Ki = 170 +/- 70 nM, n = 3). Thioperamide showed
      relatively high affinity for the 5-HT3 receptor (Ki = 120 +/- 30 nM, n = 3) and
      the sigma receptor (Ki = 180 +/- 90 nM, n = 3). 5. Due to the low density of
      histamine H3 receptors in the brain, the interaction of IPP with the 5-HT3-, the
      alpha 2- and the sigma receptor might interfere with [125I]-IPP binding to rat
      cortex membranes. Yet, in this preparation [125I]-IPP binding was not influenced
      by ondansetron, yohimbine or haloperidol. The interaction with the 5-HT3 receptor
      was not restricted to IPP or thioperamide, but was alsofound with other H3
      receptor antagonists. The potent H3 receptor agonist imetit, a compound
      belongingto the same chemical class of IPP, also interacted with the 5-HT3
      receptor (Ki = 240 +/- 40 nM). In contrast,histamine or the H3 receptor agonist,
      (R)-a-methylhistamine showed no affinity for the 5-HT3 receptor.7 In the guinea
      pig isolated ileum, imetit evoked concentration-dependent contractions, resulting
      in apD2 value of 4.72 +/- 0.03 (n = 9). The contractions were antagonized by
      ondansetron, yielding a pA2 valueof 7.1 +/- 0.1 (n = 9). Similarly ondansetron
      antagonized the contractions evoked by the 5-HT3 receptoragonist, 2-methyl-5-HT
      with a pA2 value of 7.3 +/- 0.1 (n = 4). IPP and thioperamide did not mimic 2
      methyl-5-HT but non-competitively inhibited the 2-methyl-5-HT-induced
      contractions of thispreparation.8 In an in vivo model for 5-HT3 activity, the Von
      Bezold Jarisch reflex, thioperamide showedantagonism in low dosages, which
      correlated well with the affinity for the 5-HT3 receptor site. Yet, athigher
      dosages no further 5-HT3 receptor antagonism was observed. For IPP no 5-HT3
      receptor activitycould be observed in vivo.9 In the present study we showed that
      many H3 receptor compounds, that are regarded as highlyselective (including the
      prototype drug, thioperamide), also interact with the 5-HT3 receptor, albeit
      athigher drug concentrations.Keywords.: Histamine H3-receptor; iodophenpropit;
      thioperamide; receptor selectivity; 5-hydroxytryptamine 5-HT3 receptor;guinea-pig
      intestine; rat brain; Von Bezold Jarisch reflex

PMID- 8564267
TI  - Effects of pinacidil on arterial and venous resistances and mean circulatory
      filling pressure in rats.
AB  - 1. The effects of the potassium channel opener, pinacidil, on mean arterial
      pressure (MAP), mean circulatory filling pressure (MCFP), total peripheral
      resistance (TPR), cardiac output (CO) and resistance to venous return (Rv) were
      studied in rats. 2. In pentobarbitone-anaesthetized rats given mecamylamine
      (ganglionic blocker, 3.7 micrograms kg-1) and noradrenaline (1.5 micrograms kg-1
      min-1) to suppress autonomic reflexes, pinacidil (60 and 180 micrograms kg-1 min
      1), relative to the vehicle, reduced MAP and TPR in a dose-dependent manner but
      did not significantly alter CO, MCFP or RV. 3. Pinacidil (10-300 micrograms kg-1
      min-1) caused similar increases in MCFP, an inverse index of venous compliance,
      and similar dose-dependent reductions in mean arterial pressure (MAP) in
      conscious, intact rats and rats infused with the ganglionic blocker,
      hexamethonium (150 micrograms kg-1 min-1). In rats with vasomotor tone elevated
      by the infusion of noradrenaline (1.5 micrograms kg-1 min-1), pinacidil caused
      markedly greater depressor responses but did not significantly alter MCFP. 4. Our
      results show that pinacidil is an efficacious vasodilator of arterial resistance
      blood vessels but has little venodilator activity.

PMID- 8564268
TI  - The role of capacitative Ca2+ influx in the alpha 1B-adrenoceptor-mediated
      contraction to phenylephrine of the rat spleen.
AB  - 1. The mechanism of contraction to phenylephrine in the rat spleen (mediated via
      alpha 1B-adrenoceptors) has been studied in functional experiments. 2. The
      concentration-dependent contraction of the rat spleen to cumulative additions of
      phenylephrine (pD2 4.8 +/- 0.1) was not significantly reduced by the selective
      protein kinase C (PKC) inhibitor, calphostin C (10(-6)M) or potentiated by the
      DAG kinase inhibitor, R59022 (10(-6) M). 3. Contraction of the rat spleen in
      normal Krebs solution containing Ca2+ (2.5 mM) to a single concentration of
      phenylephrine (3 x 10(-4) M) produced a maximal response consisting of an initial
      phasic component and a more slowly developing tonic component. However in Ca(2+)
      free Krebs solution (containing EGTA), phenylephrine (3 x 10(-4)M) produced only
      a phasic contraction which was reduced to 46 +/- 3% maximum response to
      phenylephrine in normal Krebs solution. 4. In some tissues after the contraction
      to phenylephrine (3 x 10(-4) M) in Ca(2+)-free Krebs solution (containing EGTA),
      the phenylephrine was washed out and the tissue was allowed to recover. After 2
      h, upon addition of Ca2+ (2.5 mM) to the Krebs solution (EGTA now removed) a
      tonic contraction developed in the tissue (97 +/- 4% maximum response to
      phenylephrine). 5. Cyclopiazonic acid produced a tonic contraction of the rat
      spleen with a maximum effect at 10(-5) M (202 +/- 8% maximum response compared
      with that to phenylephrine). The contraction to CPA (10(-5) M) was reduced in
      Ca(2+)-free Krebs solution containing EGTA (30 +/- 4% of the maximum response to
      phenylephrine). One hour after the end of the contraction in Ca(2+)-free Krebs
      solution (EGTA now removed), upon addition of Ca2+ (2.5 mM) to the Krebs solution
      a tonic contraction developed in the tissue (263 +/- 12% maximum response to
      phenylephrine). 6 In Ca2+-free Krebs solution, after the spleen had been
      incubated with cyclopiazonic acid for 30 min,the subsequent contraction to
      phenylephrine (3 x 10-4 M) was reduced from 46+/-3% to 9+/-2%maximum response to
      phenylephrine.7 Cumulative contractions to phenylephrine and the contraction to
      cyclopiazonic acid (10-5 M) in the spleen were not significantly affected by
      nifedipine (10-6 M). The non-selective Ca2+channel blocker,SK&F 96365 (3 x 10-5
      M) reduced the maximum response for the cumulative additions of phenylephrine to
      35+/-1% and the contraction to CPA (10-5 M) from 202+/-8% to 108+/-8% maximum
      response to phenylephrine.8 The tyrosine kinase inhibitors genistein (3 x 10-5 M
      and tyrphostin 23 (10-4 M), reduced the maximum response to phenylephrine in the
      spleen to 51+/-4% and 44+/-5% respectively and the maximum contraction to
      cyclopiazonic acid (3 x 10-6 M) in the spleen from 132 +/- 6% to 82 +/-5% and 80
      +/- 7% maximum response to phenylephrine respectively without affecting
      contractions to K+.9 In conclusion, these results are consistent with the
      contraction of the rat spleen to phenylephrine consisting of an initial phasic
      contraction due to release of intracellular Ca2+ and a larger tonic contraction
      due to capacitative Ca2+ influx through non-voltage-gated Ca2+ channels and which
      may involve a tyrosine kinase. This suggests that inositol triphosphate but not
      diacylglycerol is involved in the contraction.

PMID- 8564270
TI  - Special issue on traumatic memory research.

PMID- 8564269
TI  - Regulation by phosphodiesterase isoenzymes of non-adrenergic non-cholinergic
      contraction in guinea-pig isolated main bronchus.
AB  - 1. We have investigated the role of phosphodiesterase isoenzymes in modulating
      electric field stimulation (EFS), substance P and capsaicin-induced contraction
      of the guinea-pig isolated main bronchus. 2. Non-adrenergic non-cholinergic
      contractile responses were elicited by EFS (3 Hz, 20 s) in the guinea-pig
      isolated main bronchus in the presence of the non-selective muscarinic
      antagonist, atropine (0.1 microM), the non-selective beta-adrenoceptor
      antagonist, propranolol (1 microM), the neutral endopeptidase inhibitor,
      thiorphan (10 microM) and the cyclo-oxygenase inhibitor, indomethacin (5 microM).
      The type III, type III/IV, type IV and type V phosphodiesterase isoenzyme
      inhibitor, SKF 94836, benzafentrine, Ro-20-1724 and zaprinast respectively,
      significantly attenuated the contractile response to EFS. The IC50 (95%
      confidence limits) value for SKF 94836, benzafentrine, Ro-20-1724 and zaprinast
      was 8.3 microM (0.89-78); 0.7 microM (0.1-4.5); 0.5 microM (0.2-1.2) and 13
      microM (2-87) respectively. 3. The phosphodiesterase isoenzyme inhibitors, SKF
      94836, Ro-20-1724 and zaprinast, partially attenuated the contractile response to
      substance P (10 nM). Benzafentrine significantly inhibited the contractile
      response to substance P, yielding an IC50 value of 1.9 microM (0.9-3.8). 4. The
      phosphodiesterase isoenzyme inhibitor, Ro-20-1724 (0.1-100 microM) failed to
      reduce significantly the contractile potency of capsaicin (P > 0.05). In
      contrast, SKF 94836 (1 microM), benzafentrine (10 microM) and zaprinast (100
      microM) significantly reduced the contractile potency of capsaicin (P < 0.05). 5
      The selective phosphodiesterase isoenzyme inhibitors, SKF 94836, benzafentrine,
      Ro-20-1724 andzaprinast (0.01-100 microM) reversed in a concentration-dependent
      manner the contractile response toexogenously administered capsaicin (EC50)
      yielding ICm values of 3.91 microM (0.68-22); 3.37 microM (1.86-6.11); 0.366
      microM (0.201-0.564) and 50.1 microM (18.6- 135) respectively.6 In conclusion,
      phosphodiesterase isoenzymes appear to regulate the contractile response to
      electricalfield stimulation and our results provide circumstantial evidence for a
      regulatory role ofphosphodiesterase type IV isoenzyme on sensory nerve function
      in vitro.

PMID- 8564271
TI  - Dissociation and the fragmentary nature of traumatic memories: overview and
      exploratory study.
AB  - Since trauma arises from an inescapable stressful event that overwhelms people's
      coping mechanisms, it is uncertain to what degree the results of laboratory
      studies of ordinary events are relevant to the understanding of traumatic
      memories. This paper reviews the literature on differences between recollections
      of stressful and of traumatic events. It then reviews the evidence implicating
      dissociation as the central pathogenic mechanism that gives rise to posttraumatic
      stress disorder (PTSD). A systematic exploratory study of 46 subjects with PTSD
      indicated that traumatic memories were retrieved, at least initially, in the form
      of dissociated mental imprints of sensory and affective elements of the traumatic
      experience: as visual, olfactory, affective, auditory, and kinesthetic
      experiences. Over time, subjects reported the gradual emergence of a personal
      narrative that can be properly referred to as "explicit memory." The implications
      of these findings for understanding the nature of traumatic memories are
      discussed.

PMID- 8564272
TI  - Functional neuroanatomical correlates of the effects of stress on memory.
AB  - Recently there has been an increase in interest in the relationship between
      stress and memory. Brain regions which are involved in memory function also
      effect the stress response. Traumatic stress results in changes in these brain
      regions; alterations in these brain regions in turn may mediate symptoms of
      posttraumatic stress disorder (PTSD). Neural mechanisms which are relevant to the
      effects of stress on memory, such as fear conditioning, stress sensitization, and
      extinction, are reviewed in relation to their implications for PTSD. Special
      topics including neural mechanisms in dissociation, neurobiological approaches to
      the validity of childhood memories as they apply to controversies over the "False
      Memory Syndrome," and implications of the effects of stress on memory for
      psychotherapy, are also reviewed. The findings discussed in this paper are
      consistent with the formulation that stress-induced alterations in brain regions
      and systems involved in memory may underlie many of the symptoms of PTSD, as well
      as dissociative amnesia, seen in survivors of traumatic stress.

PMID- 8564273
TI  - Say it once again: effects of repeated questions on children's event recall.
AB  - In this paper, we review research examining the influences of repeated
      questioning on children's event recall. Issues addressed include how children's
      free recall changes across multiple recounts of the same event, whether
      responding to specific questions about an event affects subsequent responses to
      those same questions, and whether there are developmental differences in how
      children respond to repeated questioning. Both naturalistic studies of
      conversational remembering and more controlled studies using standardized
      interviews are discussed. Effects of repeated questioning both within and across
      interviews are assessed. In integrating the research findings, we present a
      developmental framework for understanding the effects of repeated questioning
      that relies on children's developing memory and narrative skills as well as their
      social understanding of the recall context.

PMID- 8564274
TI  - Children's long-term retention of salient personal experiences.
AB  - Research on young children's long-term retention is reviewed in this article.
      More specifically, the abilities of 3- to 7-year-olds to remember the details of
      two types of medical experiences--a routine physical examination and an invasive
      radiological procedure--are discussed in the context of a framework for
      considering the flow of information in the developing memory system. The
      framework emphasizes four general themes about memory performance and provides a
      vehicle for relating research on memory development to discussions of children's
      testimony and adults' abilities to remember early experiences.

PMID- 8564275
TI  - Are rape memories different? A comparison of rape, other unpleasant, and pleasant
      memories among employed women.
AB  - The study examined empirically-measured memory characteristics, compared pleasant
      and unpleasant intense memories as well as rape and other unpleasant memories,
      and determined whether rape memories exhibited significantly more "flashbulb"
      characteristics. Data consisted of responses to a mailed survey of women
      employees of a medical center (N = 1,037) and a university (N = 2,142). Pleasant
      and unpleasant memories were differentiated by feelings, consequences, and level
      of unexpectedness. The most powerful discriminator of rape from other unpleasant
      memories was the degree to which they were less clear and vivid, contained a less
      meaningful order, were less well-remembered, and were less thought and talked
      about. Few "flashbulb" characteristics discriminated among memory types.
      Implications for clinical work with rape survivors were discussed.

PMID- 8564276
TI  - Posttraumatic stress associated with delayed recall of sexual abuse: a general
      population study.
AB  - This study examined delayed recall of childhood sexual abuse in a stratified
      random sample of the general population (N = 505). Of participants who reported a
      history of sexual abuse, 42% described some period of time when they had less
      memory of the abuse than they did at the time of data collection. No demographic
      differences were found between subjects with continuous recall and those who
      reported delayed recall. However, delayed recall was associated with the use of
      threats at the time of the abuse. Subjects who had recently recalled aspects of
      their abuse reported particularly high levels of posttraumatic symptomatology and
      self difficulties (as measured by the IES, SCL, and TSI) at the time of data
      collection compared to other subjects.

PMID- 8564277
TI  - Recovered memories of abuse in women with documented child sexual victimization
      histories.
AB  - This study provides evidence that some adults who claim to have recovered
      memories of sexual abuse recall actual events that occurred in childhood. One
      hundred twenty-nine women with documented histories of sexual victimization in
      childhood were interviewed and asked about abuse history. Seventeen years
      following the initial report of the abuse, 80 of the women recalled the
      victimization. One in 10 women (16% of those who recalled the abuse) reported
      that at some time in the past they had forgotten about the abuse. Those with a
      prior period of forgetting--the women with "recovered memories"--were younger at
      the time of abuse and were less likely to have received support from their
      mothers than the women who reported that they had always remembered their
      victimization. The women who had recovered memories and those who had always
      remembered had the same number of discrepancies when their accounts of the abuse
      were compared to the reports from the early 1970s.

PMID- 8564278
TI  - Change in rape narratives during exposure therapy for posttraumatic stress
      disorder.
AB  - This paper presents a coding system developed to explore changes in narratives of
      rape during therapy for posttraumatic stress disorder (PTSD) involving repeated
      reliving and recounting of the trauma. Relationships between narrative categories
      hypothesized to be affected by the treatment and treatment outcome were also
      examined. As hypothesized, narrative length increased from pre- to post
      treatment, percentage of actions and dialogue decreased and percentage of
      thoughts and feelings increased, particularly thoughts reflecting attempts to
      organize the trauma memory. Also as expected, increase in organized thoughts was
      correlated negatively with depression. While indices of fragmentation did not
      significantly decrease during therapy, the hypothesized correlation between
      decrease in fragmentation and reduction in trauma-related symptoms was detected.

PMID- 8564279
TI  - Factors influencing recall of childhood sexual abuse.
AB  - Selective literatures providing perspective on recall of childhood sexual abuse
      memories are reviewed. These include known patterns of autobiographical memories
      in adulthood, metacognitive mechanisms, interpersonal influences, and automatic
      cognitive processing which can influence judgments and reports of memory recall
      in children and adults. Some factors in adult experience such as mood state,
      presence of emotional disorders, past and current relationships, and
      participation in psychotherapy which can influence autobiographical memory and
      recall of childhood events are delineated. Available studies directly exploring
      recovered memories of childhood abuse are considered in light of these studies.
      Finally, some applications to clinical work and suggestions for future research
      are outlined.

PMID- 8564280
TI  - Trauma, traumatic memory, and research: where do we go from here?

PMID- 8564281
TI  - Classifications and epidemiologic considerations of epileptic seizures and
      epilepsy.
AB  - The manifestations of epileptic disorders are widely known to be extremely
      protean. Classifying the disorders is a way of achieving a common understanding
      of the terminology used in identifying seizure disorders in the clinical or
      research settings. Two International Classifications have been developed, namely
      the International Classification of Epileptic Seizures and the International
      Classification of Epilepsy and Epileptic Syndromes. The first divides epileptic
      seizures into two major categories: partial and generalized. Partial epileptic
      seizures are further classified according to the impairment or the preservation
      of consciousness into simple partial and complex partial seizures. Either
      condition may secondarily generalize into tonic-clonic seizures. Under the
      International Classification, epilepsy and epileptic syndromes are initially
      classified according to their corresponding types of seizures into localization
      related and generalized disorders. Each disorder is further classified according
      to the relationship to etiologic or predisposing factors into symptomatic,
      cryptogenic, or idiopathic types. The classifications undoubtedly will be further
      revised as more is learned about epileptic disorders with advances in
      electrophysiology, neuroimaging techniques, and molecular genetics. An overview
      of the epidemiology of epileptic disorders shows that, contrary to the popular
      belief, they are primarily disorders of childhood; age-specific incidence rates
      of first unprovoked seizure and of epilepsy are highest in the elderly. An
      appreciation of the epidemiology of seizure disorders is essential in their
      clinical and laboratory evaluation.

PMID- 8564282
TI  - Pathology of seizure disorders.
AB  - A variety of pathologic lesions associated with seizures are described in this
      article. Because of concerted efforts of workers in the field, remarkable
      progress has been made in the early detection, resection, and characterization of
      previously poorly defined pathologic processes. It is hoped that with further
      advancement of the neurosciences, most of the cryptogenic cases may be
      categorized so that the epileptogenic mechanism in individual lesions can be
      better understood.

PMID- 8564283
TI  - Clinical evaluation and noninvasive electroencephalography. Preoperative
      evaluation.
AB  - Epilepsy surgery has been shown to be a safe and effective alternative to
      antiepileptic drug therapy for many patients with medical refractory partial
      seizure disorders. Surgical treatment should be considered when the patients
      experience and impairment in the quality of life related to the seizures, medical
      therapy, or both. Surgically remediable epileptic syndromes include medical
      temporal lobe epilepsy and lesional epilepsy. A comprehensive presurgical
      evaluation is performed to identify appropriate candidates for epilepsy surgery.

PMID- 8564284
TI  - Intracranial electrophysiologic studies.
AB  - The presurgical evaluation of patients with medically refractory epilepsy begins
      with a thorough noninvasive approach, including ictal monitoring with scalp
      recording technique. The concept of convergence of evidence is used to determine
      the adequacy of the noninvasive localization. A variety of intracranial
      electrophysiologic studies can be employed when the noninvasive evaluation is
      insufficient. Intracranial studies are used for precise identification of
      eloquent cortex. The ultimate lines of resection are then designed to include as
      much of the epileptogenic zone as possible, while excluding areas of eloquent
      cortical function.

PMID- 8564285
TI  - Spike and slow wave localization by magnetoencephalography.
AB  - At institutions where MEG is available, it is now considered a standard part of
      the diagnostic workup of most patients with epilepsy. Available data indicate
      that interictal MEG can be an effective tool for localization of the epileptic
      irritative zone, and in some cases it can even indicate the seizure onset site.
      Both spike and ALFMA examinations are clinically viable because of the
      availability of large-array systems. The current cost of acquiring MEG technology
      is high (greater than 2 million dollars), but recent technical developments
      should soon yield more cost-effective systems. It is anticipated that the
      increasing applicability of this technology to conditions beyond epilepsy (e.g.,
      head trauma, ischemic disease, dementia, and psychiatric dysfunction) will soon
      render MEG a critical element in the general armamentarium of diagnostic
      procedures available to epileptologists, radiologists, neurologists,
      neurosurgeons, and psychiatrists.

PMID- 8564286
TI  - Magnetic resonance imaging. Neuroimaging and anatomy.
AB  - The histologic substrates of epilepsy can be divided into five major categories:
      tumor, disorders of neuronal migration and cortical organization, vascular
      malformation, mesial temporal sclerosis, and neocortical sclerosis secondary to
      brain injury. Magnetic resonance imaging is the most sensitive and specific
      imaging technique for the noninvasive identification of each of these
      epileptogenic substrates. Introduction of magnetic resonance imaging into
      clinical practice over the past 10 years has significantly changed the management
      of patients with epilepsy. It has also begun to redefine the classification of
      the epilepsies in terms of histologic substrates. This article focuses on the
      clinical role of magnetic resonance imaging in symptomatic epilepsy, the
      histologic substrates of epilepsy, and their magnetic resonance image appearance.

PMID- 8564287
TI  - Use of positron emission tomography for the evaluation of epilepsy.
AB  - After a brief introduction to the theoretic aspects of positron emission
      tomography, four areas of positron emission tomography research are discussed
      with an emphasis on current concepts and future directions. The use of positron
      emission tomography as a tool for the localization of the pathologic brain region
      and as a predictor of surgical outcome in focal epilepsy is reviewed and compared
      with the sensitivity, specificity, and outcome predicted by other neuroimaging
      techniques. Research on positron emission tomography measures of regional
      metabolism, bloodflow, and neuroreceptors is reviewed from the perspective of
      epileptic pathophysiology with a special emphasis on elucidative integrative
      neural circuits involved in epileptic spread and termination. A brief review and
      discussion of the use of positron emission tomography for the understanding of
      potential neural reorganization of cognitive processes in epilepsy follows. In
      the final section, an overview of recently developed methods of positron emission
      tomography data analysis with a focus on application to research questions in
      epilepsy is presented.

PMID- 8564288
TI  - Single photon emission computed tomography.
AB  - Single-photon emission computed tomography is a well established functional
      imaging technique in epilepsy that aids precise noninvasive localization of the
      seizure focus required for surgical intervention in refractory seizures.
      Electroencephalography with video monitoring of seizures precedes more invasive
      evaluation, such as cortical or depth electrodes. Positron emission tomography
      studies in temporal lobe epilepsy are moderately sensitive, demonstrating
      ipsilateral hypometabolism. Ictal single photon emission computed tomography
      studies in temporal lobe epilepsy demonstrate transient intense hyperemia in the
      anterior temporal lobe structures. Peri-ictal images show persisting mesial
      temporal hyperperfusion with lateral hypoperfusion developing over the next 2 to
      5 minutes to be replaced by significant hypoperfusion in the postictal phase.
      Interictal single photon emission computed tomography with ipsilateral
      hypoperfusion, suffers from reduced sensitivity and accuracy, whereas ictal and,
      to a lesser extent, peri-ictal and postictal single photon emission computed
      tomography are highly sensitive and accurate in localizing temporal lobe
      epilepsy. New iodinated neuroreceptor single photon emission computed tomography
      imaging agents hold promise in localizing the seizure focus (focally reduced
      uptake) without ictal injection, and also may elucidate underlying mechanisms
      inherent to epilepsy.

PMID- 8564289
TI  - Magnetic resonance spectroscopy.
AB  - Magnetic resonance spectroscopy, like PET, allows cerebral function to be
      assessed neuro-anatomically. In addition to being noninvasive and not requiring
      ionizing radiation, this technique can be performed with equipment available at
      most medical centers. Initial studies suggest both proton and phosphorous
      spectroscopy will be useful adjunctive presurgical tests for the localization of
      the epileptogenic foci in patients with partial epilepsy, especially those with
      extratemporal foci. Furthermore, MRS imaging may prove to be a useful tool for
      studying the response to medical treatment and the pathophysiologic basis of
      epilepsy.

PMID- 8564291
TI  - Functional localization by magnetoencephalography.
AB  - Magnetoencephalography combines the attributes of real-time millisecond temporal
      resolution with precise anatomic localization. In addition to characterizing
      spontaneous epileptiform discharges and slow wave activity,
      magnetoencephalography may be used to map sensorimotor, auditory, and visual
      functions. Magnetoencephalography functional data are registered to three
      dimensional magnetic resonance imaging to provide a useful way to analyze the
      relationship of structure to function and to assist in surgical planning.
      Magnetoencephalography is noninvasive and can be done with rapid turn-around
      time, but it is expensive and is not optimal for all brain areas or functions.
      Future integration and cross-analysis of magnetoencephalography with other
      functional mapping modalities will likely prove to be complementary and of even
      greater use.

PMID- 8564292
TI  - Transcranial magnetic stimulation.
AB  - Multiple techniques are vying for establishing the new gold standard for
      functional cortical mapping, displacing that of the currently invasive and risk
      prone techniques of subdural electrode arrays and intraoperative electrical
      stimulation mapping. Transcranial magnetic stimulation holds promise for
      functional localization of primary motor areas and speech areas, and possibly
      even other higher cortical functions. The technique is economical, especially
      when compared with the cost of functional magnetic resonance imaging and positron
      emission tomography. It can be performed effectively and safely in patients with
      epilepsy.

PMID- 8564290
TI  - Functional MR imaging in the evaluation of the patient with epilepsy. Functional
      localization.
AB  - Functional magnetic resonance imaging is able to define noninvasively the
      location of eloquent cortex responsible for speech, motor, and visual function,
      and it holds promise for localizing other important functional tissues in the
      future. Such localization is extremely important to the epileptologist and
      surgeon planning surgical resection of an epileptic focus. Early work identifies
      the actual seizure focus using similar techniques. Magnetic resonance, with
      functional magnetic resonance added to high-resolution magnetic resonance imaging
      and magnetic resonance spectroscopy, has the potential of providing, in a cost
      effective manner with one noninvasive modality, the functional, anatomic, and
      chemical parameters pertinent to the management of the seizure patient.

PMID- 8564293
TI  - Intracarotid amobarbital procedure. The Wada test.
AB  - Wada testing has been a standard part of temporal lobectomy evaluation since the
      early 1960s. Although the procedure was initially used to lateralize language
      function, it was soon modified to assess risk for postoperative amnesia. The use
      of the procedure has now evolved to include prediction of degrees of memory
      decline. This use has been criticized, but more recent research has better
      described important parameters of the procedure and supported its validity. The
      Wada test is effective in lateralizing seizure onset, predicting postoperative
      seizure control, and predicting degree of verbal memory decline following left
      temporal lobectomy. The validity of Wada test data has also been supported by
      correlations between Wada memory performance and hippocampal pyramidal cell loss
      or MR imaging determined hippocampal volumes. It remains to be seen, however, if
      Wada memory performance and data from other sources such as MR imaging, ictal
      SPECT, positron emission tomography, or functional MR imaging are redundant or
      independently contribute to patient diagnosis and management.

PMID- 8564295
TI  - Characterization of DNA-binding proteins involved in the assembly of
      mitochondrial nucleoids in the yeast Saccharomyces cerevisiae.
AB  - Mitochondrial nucleoids (mt-nucleoids) isolated from the yeast Saccharomyces
      cerevisiae were analyzed to identify the protein components that are involved in
      the compact packaging of mtDNA. The isolated mt-nucleoids were disassembled by
      the addition of 2 M NaCl and the disassembled mt-nucleoids were reassembled once
      again into compact structures by dialysis against a buffer that contained NaCl at
      concentrations below 0.1 M, as monitored by staining of the DNA with 4',6
      diamidino-2-phenylindole. DNA-binding proteins with molecular masses of 67 kDa,
      52 kDa, 50 kDa, 38 kDa, 30 kDa and 20 kDa were separated from isolated mt
      nucleoids by column chromatography on DNA-cellulose after digestion of mt
      nucleoids by DNase I in the presence or absence of 2 M NaCl. Purified mtDNA was
      compactly packaged into nucleoid-like structures upon the addition of fractions
      that contained DNA-binding proteins and subsequent dialysis to reduce the
      concentration of NaCl. Five proteins, with molecular masses of 67 kDa, 52 kDa, 50
      kDa, 38 kDa and 30 kDa, respectively, had lower affinity for double-stranded DNA
      than that of the 20-kDa protein. The fraction that contained the five DNA-binding
      proteins other than the 20-kDa protein was also able to fold mtDNA compactly into
      nucleoid-like structures. By contrast, the combination of the 20-kDa protein and
      mtDNA resulted in formation of less tightly packed, string-of-bead structures.
      These results suggest that at least six different DNA-binding proteins are
      involved in the organization of the mt-nucleoids.

PMID- 8564294
TI  - Epilepsy surgery.
AB  - Epilepsy surgery is an important treatment for many patients with seizures
      refractory to medical therapy. In this article, the background for this surgery
      is discussed, and the most common operations reviewed. With early diagnosis and
      successful surgery, many patients can be returned to active and productive lives.

PMID- 8564296
TI  - Effects of gibberellins on seed germination of phytochrome-deficient mutants of
      Arabidopsis thaliana.
AB  - Experiments were carried out to explore the involvement of gibberellins (GAs) in
      the light-induced germination of Arabidopsis thaliana (L.) Heynh, using wild type
      (WT) and phytochrome-deficient mutants (phyA, phyB and phyAphyB deficient in
      phytochrome A, B and A plus B, respectively). Seed germination of WT and
      phytochrome-deficient mutants was inhibited by uniconazole (an inhibitor of an
      early step in biosynthesis of GA, the oxidation of ent-kaurene) and prohexadione
      (an inhibitor of late steps, namely, 2 beta- and 3 beta-hydroxylation). This
      inhibition was overcome by simultaneous application of 10(-5) M GA4. The relative
      activity of GAs for promoting germination of uniconazole-treated seeds was GA4 >
      GA1 = GA9 > GA20. The wild type and the phyA and phyB mutants had an increased
      response to a red light pulse in the presence of GA1, GA4, GA9, GA20 and GA24 but
      there were no significant differences in activity of each GA between the mutants.
      Therefore, neither phytochrome A nor hytochrome B appears to regulate GA
      biosynthesis from GA12 to GA4 during seed germination, since the conversion of
      GA12 to GA9 is regulated by one enzyme (GA 20-oxidase). However, GA
      responsiveness appears to be regulated by phytochromes other than phytochromes A
      and B, since the phyAphyB double mutant retains the photoreversible increased
      response to GAs after a red light pulse.

PMID- 8564297
TI  - Callose synthesis in spirostanol treated carrot cells is not triggered by
      cytosolic calcium, cytosolic pH or membrane potential changes.
AB  - Carrot (Daucus carota L.) cell suspensions were treated with a spirostanol
      saponin from Yucca. This saponin is an elicitor of callose synthesis.
      Irrespectively of the mode of action of spirostanol on the callose synthase
      activity itself, the spirostanol-induced callose synthesis in carrot is not
      preceded by changes in membrane potential, cytosolic free calcium or cytosolic
      pH. The inability of modulators of cytosolic free calcium content (verapamil,
      nifedipine and Br-A23187), EGTA and a proton pump inhibitor (vandate) to inhibit
      or induce callose formation is consistent with a calcium- and pH-independent
      mechanism for callose deposition.

PMID- 8564298
TI  - Cloning and sequencing of a cDNA for poplar endo-1,4-beta-glucanase.
AB  - A cDNA for poplar endo-1,4-beta-glucanase was cloned by use of a synthetic
      oligonucleotide as probe. The probe was designed on the basis of the N-terminal
      amino acid sequence of the beta-glucanase from suspension-cultured poplar cells
      (Populus alba L.), and by complete nucleotide sequence of the cDNA was
      determined. The 1,614-bp cDNA contained an open reading frame of 1,482 base
      pairs, encoding 494 amino acids. Removal of a putative signal sequence from the
      deduced amino acid sequence of the polypeptide yielded a mature protein of 467
      amino acids. Comparison of deduced amino acid sequences revealed that the poplar
      endo-1,4-beta-glucanase was 80% and 70% identity to avocado fruit and bean
      abscission endo-1,4-beta-glucanases, respectively. Hydropathy plot analysis of
      the deduced amino acid sequence suggests that poplar endo-1,4-beta-glucanase
      belongs to family E in terms of the cellulase catalytic domain, and avocado fruit
      and abscission bean endo-1,4-beta-glucanases also belong to this family. 2,4-D
      markedly increased the level of the endo-1,4-beta-glucanase mRNA in cultured
      cells, while GA3, benzyladenine and abscisic acid each repressed transcription of
      this mRNA. The transcript was also detected in the roots and stems of intact
      plants, although the level of mRNA was much lower in intact tissues than in
      cultured cells. Genomic Southern analysis indicated that a small family of gene
      for endo-1,4-beta-glucanase exists in poplar.

PMID- 8564299
TI  - Molecular cloning of members of the S-multigene family in self-incompatible
      Brassica campestris L.
AB  - We isolated 12 groups of genomic clones that contained SLG-homologous regions
      from a genomic library constructed from an S9 homozygote of self-incompatible
      Brassica campestris. Both SLG9 and SRK9 genomic clones, which are located within
      the self-incompatibility (S) locus, were included in these groups. The promoter
      regions of SLG9 and SRK9 were completely identical for at least 200 bp upstream
      from their respective initiation codons (ATG). The five sequence elements (boxes
      I to V) that are conserved in the promoters of SLG and SRK genes were also found
      in the SLG9 and SRK9 clones. However, one conserved element (box III)
      unexpectedly lacked 7 of 11 bp, although box III has been considered necessary
      for expression in pistil. The other ten groups of genomic clones were classified
      into six SRK-like groups and four SLG-like groups. These results indicate that
      SLG, SRK, SLG-like, and SRK-like genes form a large S-multigene family in B.
      campestris.

PMID- 8564300
TI  - A far-upstream sequence of the wheat histone H3 promoter functions differently in
      rice and tobacco cultured cells.
AB  - The cis-regulatory function of a far-upstream sequence (-1,711 to -186) of the
      promoter of the wheat gene for histone H3 (TH012) was analyzed in cultured rice
      and tobacco cells in a transient expression system with the gene for beta-D
      glucuronidase as a reporter gene. The far-upstream sequence was necessary for
      full activity of the H3 promoter in rice cells but did not enhance the activity
      of the proximal promoter in tobacco cells. Dissection analysis of the far
      upstream sequence revealed the existence of several positive and negative cis
      acting sequences in this region, some of which functioned differently in rice and
      tobacco cells. In gain-of-function experiments with rice cells, the sequence from
      -848 to -704, containing the CCAAT and octamer (CaCGGATC) motifs, functioned in
      an orientation-independent manner, whereas the sequence from -703 to -486
      functioned in an orientation-dependent manner. By contrast, both sequences
      exhibited an orientation-dependent cis-function in tobacco cells. These findings
      suggest that some cis-regulatory sequences in the far-upstream region of the H3
      promoter function differently in rice and tobacco cells.

PMID- 8564301
TI  - Isolation and characterization of two cDNAs encoding 4-coumarate:CoA ligase in
      Lithospermum cell cultures.
AB  - Two near full-length cDNAs (LE4CL-1, LE4CL-2), which encode 4-coumarate:CoA
      ligase (4CL), were cloned from a library of Lithospermum erythrorhizon cell
      suspension cultures by the use of heterologous probe of potato 4CL. These cDNAs
      are 2.1 kb and 2.2 kb in length, respectively. LE4CL-1 encodes 636 amino acids,
      whose homologies to the 4CL protein sequences known to potato, parsley, pine and
      rice, were found to be 68%, 66%, 56% and 50% (identities on amino acid level),
      respectively, whereas those of the predicted translation product of LE4CL-2 (594
      amino acids) to the above 4CL proteins were 49 approximately 54%. The similarity
      of the deduced amino acid sequences between the two 4CLs from Lithospermum cell
      cultures was 49% in identity. Northern analyses showed that the mRNA levels of
      both LE4CL-1 and LE4CL-2 were much higher under illumination than in the dark, as
      reported for the 4CL genes of such plants as parsley. In comparison of mRNA
      levels of LE4CL-1 and LE4CL-2, the former was demonstrated to be generally higher
      than the latter by means of an application of RT-PCR. The genomic southern blot
      experiments suggested that there are probably three copies of LE4CL-1 in the
      Lithospermum genome DNA, whereas only one copy was detected for LE4CL-2.

PMID- 8564302
TI  - Effects of sulfate concentrations on the expression of a soybean seed storage
      protein gene and its reversibility in transgenic Arabidopsis thaliana.
AB  - Transgenic expression of genes encoding the alpha' and beta subunits of beta
      conglycinin, one of the major seed storage proteins of soybean (Glycine max [L.]
      Merr.), was analyzed in Arabidopsis thaliana (L.) Heynh. under conditions of
      sulfate deficiency. Temporal patterns of expression of both the intact beta
      subunit gene and the beta subunit gene promoter fused to the beta-glucuronidase
      (GUS) gene are similar in soil-less cultures using rockwool, suggesting that the
      response to sulfate deficiency is regulated mainly at the level of transcription.
      In hydroponic cultures with various concentrations of sulfate, expression of both
      the intact beta subunit gene and the beta subunit gene promoter-GUS fusion gene
      were negatively correlated to increased sulfate concentrations in the culture
      medium. Transfer of transgenic A. thaliana plants carrying the beta subunit gene
      promoter-GUS fusion from sulfate-deficient to sulfate-sufficient control medium
      caused GUS activity in developing siliques to be repressed within two days. A
      reverse shift, where the plants were transferred from the control to sulfate
      deficient medium, caused GUS activity to become higher than that in seeds of the
      control plants within two days. These results indicate that the expression of the
      beta subunit gene promoter responds rapidly to changes of sulfate availability.

PMID- 8564303
TI  - A recombinant rice 16.9-kDa heat shock protein can provide thermoprotection in
      vitro.
AB  - It is difficult to obtain large amounts of purified low-molecular-mass heat shock
      proteins (LMM HSPs), which are unique to plants, for biochemical and
      physiological studies. Therefore, an attempt was made to produce such a HSP by
      applying recombinant DNA technology. We fused the cDNA for a rice class I 16.9
      kDa HSP, pTS1, to the gene for glutathione S-transferase (GST) of Schistosoma
      japonicum and we obtained large amounts of the fusion protein from transformed
      Escherichia coli cells. In addition, we found that the 16.9-kDa HSP obtained by
      cleavage of the recombinant protein could also form a protein complex of
      approximately 310 kDa under nondenaturing conditions as can the small, native,
      class I HSPs from heat-shocked rice seedlings. An assay in vitro to examine the
      thermoprotection of rice soluble proteins from heat denaturation revealed the
      strong stabilizing effect of the recombinant HSP.

PMID- 8564304
TI  - Cytokinin induces a rapid decrease in the levels of mRNAs for catalase, 3-hydroxy
      3-methylglutaryl CoA reductase, lectin and other unidentified proteins in
      etiolated cotyledons of cucumber.
AB  - Large-scale differential hybridization was performed to examine rapid changes in
      gene expression caused by a phytohormone, cytokinin, in etiolated cotyledons of
      cucumber (Cucumis sativus L.). We isolated 86 cDNA clones for mRNAs whose levels
      decreased within 2 h of the start of treatment with N6-benzyladenine (BA).
      Partial nucleotide sequences showed that some of the cDNAs were homologous to
      those for catalase, 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) and a lectin.
      This is the first report that the levels of the mRNAs for those proteins are
      regulated by a cytokinin in darkness. Together with previous results [Teramoto et
      al. (1993) Physiol. Plant. 87: 584, (1994) Planta 193: 573, (1995) Planta 196:
      387], the present study suggests that the cytokinin act to lower the levels of
      mRNAs transcribed from various genes in etiolated cotyledons.

PMID- 8564305
TI  - Touch-inducible genes for calmodulin and a calmodulin-related protein are located
      in tandem on a chromosome of Arabidopsis thaliana.
AB  - Genes for calmodulin and calmodulin-related proteins in Arabidopsis are up
      regulated by a variety of physical stimuli, which include rain, wind and touch
      [Braam and Davis (1990) Cell 60: 357]. We have isolated five genes for calmodulin
      (AtCAL1, 2, 3, 5, 6) and one gene for a calmodulin-related protein (AtCAL4) from
      an Arabidopsis genomic library. Touch stimulus of Arabidopsis plants induces the
      accumulation of mRNA transcribed from AtCAL4 and AtCAL5, but not from the other
      isolated genes. The two touch-inducible genes are arrayed in tandem with a short
      intergenic region of 700 bp but they show different organ-specific patterns of
      expression.

PMID- 8564306
TI  - Potential transcription regulatory sequences in a promoter region of the wheat
      basic/leucine zipper protein HBP-1b(c38) gene.
AB  - A gene encoding the wheat transcription factor HBP-1b(c38) and its promoter
      region have been structurally analyzed. Protein-DNA interaction studies indicated
      the specific binding of the hexamer motif ACGTCA found in the promoter to the HBP
      1b isoforms including HBP-1b(c38), suggesting that transcription of the HBP
      1b(c38) gene may be autoregulated.

PMID- 8564307
TI  - Purification and characterization of phosphoribulokinase from the cyanobacterium
      Synechococcus PCC7942.
AB  - Phosphoribulokinase (PRK) was purified to electrophoretic homogeneity from
      Synechococcus PCC7942 with high specific activity. Molecular masses of the native
      enzyme and its subunit were 178 and 42 kDa, respectively. Cys-17 and Cys-38 were
      conserved in the cyanobacterial PRK, but 18 amino acid residues between them were
      missing among the 40 residues found in higher plant PRKs.

PMID- 8564308
TI  - Tobacco nuclear genes for Photosystem I subunits, psaD, psaE and psaH share an
      octamer motif bound with nuclear proteins.
AB  - In Nicotiana sylvestris, nuclear-encoded photosystem I (PSI) genes, psaD, psaE
      and psaH, share an octamer motif bound with three phosphoproteins. This motif is
      not found in the chloroplast genome. From the view point of endosymbiont
      hypothesis, these results suggest that a set of ancient PSI genes acquired a
      common cis-element in the nucleus after they were transferred from the ancestral
      organelle.

PMID- 8564309
TI  - Informed consent in chronic schizophrenia?

PMID- 8564310
TI  - Lithium revisited. A re-examination of the placebo-controlled trials of lithium
      prophylaxis in manic-depressive disorder.

PMID- 8564311
TI  - Selective serotonin reuptake inhibitors and tricyclic antidepressants in
      combination. Interactions and therapeutic uses.
AB  - BACKGROUND: The selective serotonin reuptake inhibitors (SSRIs) are now widely
      used in the treatment of depressive illness. Interest has grown in the use of
      SSRIs as alternatives to tricyclic antidepressants (TCAs) and in the therapeutic
      use of combinations of SSRIs and TCAs in refractory depression. METHOD: MEDLINE
      and PSYCLit literature searches were conducted. Reference sections from papers
      retrieved were scrutinised for other relevant reports. RESULTS: Of 41 relevant
      articles identified, 35 were selected for review. CONCLUSIONS: Fluoxetine,
      fluvoxamine, paroxetine and sertraline may substantially increase TCA plasma
      levels when given concurrently. Such interactions may give rise to adverse
      effects. The effect of sertraline may be less profound than that of fluoxetine,
      fluvoxamine and paroxetine. Limited data suggest that citalopram may not affect
      TCA serum levels. There is scant literature evidence to support the use of SSRIs
      in combination with TCAs as a treatment for refractory depression.

PMID- 8564312
TI  - Psychotherapy for bipolar disorder.
AB  - BACKGROUND: Psychosocial factors may contribute 25-30% to the outcome variance in
      bipolar disorders. Sufferers have identified benefits from psychotherapy, but
      biological models and treatments dominate the research agenda. The author reviews
      research on psychosocial issues and interventions in this disorder. METHOD:
      Research on adjustment to the disorder, interpersonal stressors and obstacles to
      treatment compliance were located by computerised searches and the author's
      knowledge of the literature. All published outcome studies of psychosocial
      interventions in bipolar disorder are reviewed. RESULTS: There is an inadequate
      database on psychosocial factors associated with onset and maintenance of bipolar
      disorder. While the outcome studies available are methodologically inadequate,
      the accumulated evidence suggests that psychosocial interventions may have
      significant benefits for bipolar sufferers and their families. CONCLUSIONS: Given
      the significant associated morbidity and mortality, there is a clear need for
      more systematic clinical management that addresses psychosocial as well as
      biological aspects of bipolar disorder. The author identifies appropriate
      research strategies to improve knowledge of effective psychosocial interventions.

PMID- 8564313
TI  - The Camberwell Assessment of Need: the validity and reliability of an instrument
      to assess the needs of people with severe mental illness.
AB  - BACKGROUND: People with severe mental illness often have a complex mixture of
      clinical and social needs. The Camberwell Assessment of Need (CAN) is a new
      instrument which has been designed to provide a comprehensive assessment of these
      needs. There are two versions of the instrument: the clinical version has been
      designed to be used by staff to plan patients' care; whereas the research version
      is primarily a mental health service evaluation tool. The CAN has been designed
      to assist local authorities to fulfil their statutory obligations under the
      National Health Service and Community Care Act 1990 to assess needs for community
      services. METHOD: A draft version of the instrument was designed by the authors.
      Modifications were made following comments from mental health experts and a
      patient survey. Patients (n = 49) and staff (n = 60) were then interviewed, using
      the amended version, to assess the inter-rater and test-retest reliability of the
      instrument. RESULTS: The mean number of needs identified per patient ranged from
      7.55 to 8.64. Correlations of the inter-rater and test-retest reliability of the
      total number of needs identified by staff were 0.99 and 0.78 respectively. The
      percentage of complete agreement on individual items ranged from 100-81.6% (inter
      rater) and 100-58.1% (test-retest). CONCLUSIONS: The study suggests that the CAN
      is a valid and reliable instrument for assessing the needs of people with severe
      mental illness. It is easily learnt by staff from a range of professional
      backgrounds, and a complete assessment took, on average, around 25 minutes.

PMID- 8564314
TI  - Characteristics of outcome in schizophrenia at 13 years.
AB  - BACKGROUND: This paper describes the 13-year outcome of an epidemiologically
      defined and representative cohort of patients selected when they were
      experiencing their first episode of schizophrenia. METHOD: In a 13-year follow-up
      study of a cohort identified in Nottingham in 1978-80, the outcome (symptoms,
      disability, residence and treatment) was assessed using standardised instruments.
      RESULTS: Four of the original 67 patients with ICD-9 schizophrenia were lost to
      follow-up and five were dead: 52% were without psychotic symptoms in the last two
      years of follow-up, 52% were without negative symptoms and 55% showed good/fair
      social functioning. However, only 17% were alive at follow-up, without symptoms
      and disability, and receiving no treatment. CONCLUSIONS: The findings reported
      are similar to those of other long-term follow-up studies of schizophrenia and
      also to 5-year follow-up studies. Kraepelin's emphasis on the longitudinal
      implications of a diagnosis of schizophrenia are supported, but may be over
      pessimistic.

PMID- 8564315
TI  - Determinants of the extremes of outcome in schizophrenia.
AB  - BACKGROUND: Although poor prognosis has been considered a defining characteristic
      of schizophrenia, long-term studies show marked heterogeneity of outcome. METHOD:
      Assessments of positive and negative symptoms, premorbid and current IQ, and
      months of in-patient care made in an outcome study of 342 schizophrenic patients
      were categorised by severity. Determinants of these categorisations were sought
      from the historical variables available, using analysis of variance. Vignettes of
      patients with the best and worst symptomatic outcomes were then compared.
      RESULTS: Negative symptoms were associated with early onset, male sex and poor
      academic record. Positive symptoms were associated with occupational decline.
      Cognitive decline was associated with occupational variables, and in-patient care
      with academic and occupational variables. The vignettes showed that good outcome
      was associated with family psychiatric history and poor outcome with
      unavailability of family history. CONCLUSIONS: The findings support the view that
      the most malignant form of schizophrenia is neurodevelopmental, but poor outcome
      was clearly associated with family fragmentation.

PMID- 8564316
TI  - The Nithsdale Schizophrenia Surveys. XIV: Plasma lipid peroxide and serum vitamin
      E levels in patients with and without tardive dyskinesia, and in normal subjects.
AB  - BACKGROUND: Tardive dyskinesia (TD) may be mediated through free radical damage
      to neurons. Plasma lipid peroxide levels are a measure of radical damage to fats.
      Vitamin E is a free radical scavenger. METHOD: One hundred and twenty-eight
      schizophrenic patients were examined for TD using the Abnormal Involuntary
      Movements Scale. Blood samples were taken to measure plasma lipid peroxide, serum
      vitamin E and cholesterol, and vitamin E:cholesterol ratios. Twenty-four patients
      were also examined in October 1993, January 1994, and April 1994. Biochemical
      results were compared in 81 patients and 79 normal subjects. RESULTS: Patients
      with and without TD did not differ in median plasma lipid peroxide and serum
      vitamin E levels, or vitamin E:cholesterol ratios. Correlations between seasonal
      change scores in TD and biochemical measurements were low. Lipid peroxide levels
      were higher and vitamin E:cholesterol ratios lower in patients than in normal
      subjects. Vitamin E levels were lowest in in-patients and in those living in
      supported accommodation. CONCLUSIONS: The results do not support the hypothesis
      that TD is mediated through free radical damage to neurons, but suggest increased
      free radical activity in schizophrenia.

PMID- 8564317
TI  - Effect of emotional salience on thought disorder in patients with schizophrenia.
AB  - BACKGROUND: This study examined the effect of emotional salience on the severity
      of thought disorder in schizophrenic patients. METHOD: Ten thought disordered and
      ten non-thought disordered schizophrenic patients were interviewed under two
      conditions: a personal interview involving material which was emotionally salient
      and an impersonal interview involving material which was not emotionally salient.
      RESULTS: Both groups exhibited some thought disorder during both interviews. The
      thought disordered patients exhibited significantly more thought disorder during
      the emotionally salient interview. CONCLUSIONS: Thought disorder in schizophrenic
      patients is affected by the emotional salience of the material being discussed.
      Clinical implications are discussed.

PMID- 8564318
TI  - Insight and psychotic illness. Cross-sectional and longitudinal associations.
AB  - BACKGROUND: Insight has recently re-emerged as an important aspect of
      psychopathology amenable to empirical study. We sought to examine the
      relationship between various aspects of insight into illness and clinical,
      sociodemographic and neuropsychological variables. METHOD: From an inner-London
      catchment area population, 150 in-patients with recent onset of psychosis were
      assessed on a variety of measures, including the Present State Examination (PSE).
      Subjects were followed up for a mean of four years and reassessed. RESULTS: High
      IQ was associated with better insight as rated on the PSE, while gender,
      ethnicity and a diagnosis of schizophrenia appeared to be unrelated. At follow
      up, similar associations were found, as well as correlations with attitudes to
      treatment and a more elaborate measure of insight. Cerebral ventricular
      enlargement and tests of frontal lobe function did not correlate with insight,
      but there was a curious, strong association with left-handedness at both
      assessment points. Initial insight correlated significantly but weakly with
      insight at follow-up. CONCLUSIONS: The assessment of insight in psychosis has
      concurrent validity and is a distinct aspect of psychotic phenomenology. It may,
      in part, have a neuropsychological basis.

PMID- 8564319
TI  - Regional cerebral blood flow in obsessive-compulsive disordered patients at rest.
      Differential correlates with obsessive-compulsive and anxious-avoidant
      dimensions.
AB  - BACKGROUND: We tested whether cortical and subcortical regional cerebral blood
      flow (rCBF) differs between patients with obsessive-compulsive disorder (OCD) and
      healthy controls. We then explored the relationship between rCBF and OCD mental
      state. METHOD: Thirty out-patients from the Maudsley Hospital with OCD as defined
      in DSM-III-R were scanned at rest using brain-dedicated, high-resolution, single
      photon emission tomography. RCBF was measured as uptake of 99mTc-HMPAO in 15
      regions of interest and compared with rCBF data in 30 healthy people matched for
      age, sex and handedness. Symptom ratings were obtained using standard measures on
      the scanning day. Principal components factor analysis identified two distinct
      clinical dimensions: obsessive-compulsive (OC) and anxious-avoidant (AA). These
      were correlated with patients' rCBF measurements, using Spearman's rank
      correlation coefficient, and multiple regression coefficients calculated.
      RESULTS: We found significant reductions in rCBF measurements of OCD patients
      compared with resting, healthy controls (F = 1.92, P = 0.04) in seven brain
      regions: the right and left superior frontal cortex, right inferior frontal
      cortex, left temporal cortex, left parietal cortex, right caudate nucleus and
      right thalamus. Regional differences were not secondary to generalised reduction
      in patients' brain perfusion. Reduced blood flow to the right inferior frontal
      cortex correlated significantly with illness severity (r = 0.37, P = 0.02). There
      was no relationship with age, age-of-onset, sex, handedness, depression or
      medication status. OC clinical dimension, concerning obsessions, compulsions and
      low mood, was significantly negatively correlated with left inferior frontal,
      medial frontal and right parietal rCBF. AA dimension, concerning anxiety and
      avoidance, was significantly positively associated with left and right superior
      frontal, right inferior frontal, medial frontal cortical, and right and left
      caudate and thalamic rCBF. CONCLUSIONS: rCBF differs significantly between
      resting OCD patients and healthy controls, and separate clinical dimensions are
      associated with functionally distinct rCBF patterns.

PMID- 8564320
TI  - A controlled study of cognitive behaviour therapy with buspirone or placebo in
      panic disorder with agoraphobia.
AB  - BACKGROUND: This multicentre study compared a 16-week buspirone treatment with
      placebo in patients presenting with panic disorder with agoraphobia and also
      receiving cognitive behaviour therapy (CBT). METHOD: Double-blind testing was
      maintained until week 68, but not tested; 91 patients were included; 14 placebo
      responders excluded; 77 patients randomised; 48 reached week 16 and 41 reached
      week 68. RESULTS: At week 16, within-group analysis showed significant
      improvements in agoraphobia, panic attacks, and depression in both groups.
      Generalised anxiety improved only in CBT+buspirone. Between-group comparisons
      showed buspirone to have an effect on generalised anxiety and agoraphobia.
      Changes in degree of agoraphobia and depression were correlated in subjects on
      CBT+buspirone only. A significantly higher proportion of women, and of subjects
      showing high avoidance dropped out. Positive expectations regarding medication
      predicted success in both groups. At week 68, improvement was retained without
      significant buspirone effect. CONCLUSION: Buspirone enhanced the effects of
      cognitive behaviour therapy on generalised anxiety and agoraphobia in the short
      term.

PMID- 8564321
TI  - A prevalence study of age-associated memory impairment.
AB  - BACKGROUND: Age-associated memory impairment (AAMI) describes a non-disease
      ageing-related decline in memory. Pharmacological treatment trials have been
      reported and DSM-IV has introduced a term for the disorder. No prevalence study
      with the original criteria has previously been published. METHOD: An age
      stratified sample was taken of 50-95-year-olds registered with a local health
      centre. Diagnosis of AAMI was made by questionnaire, cognitive testing, and
      medical and psychiatric assessment. RESULTS: Prevalence rates for the total
      population and for the over-50s were estimated to be 5.8% and 18.5%,
      respectively. These rates are dramatically affected by minor alterations to
      individual criteria. CONCLUSIONS: It appears AAMI is less common than previous
      estimates suggested, although the diagnostic criteria do not satisfactorily
      define people with an age-related decline in memory. Complaint of memory decline
      is more strongly correlated with measures of affect and personality than with
      measures of current memory test performance or estimates of memory decline.

PMID- 8564322
TI  - Depression in later life. A comparison of symptoms and risk factors in early and
      late onset cases.
AB  - BACKGROUND: Depression in later life is often thought to differ from that at
      other times of adulthood. The evidence for this is controversial but is important
      to any proposed organic model of depression in the elderly. Here, early- and late
      onset depressions in later life are compared. METHOD: Fifty-seven depressed
      patients with a mean age of 74 were studied, 21 with an early onset (aged 59 or
      less) and 36 with a late onset. All were suffering from major depression
      according to DSM-III-R. The measures at entry included severity and symptoms,
      cognitive function, antecedent life events, physical health and vascular risk
      factors and/or vascular disease. We also recorded any family history of mood
      disorders, as well as the course of illness. RESULTS: The anxiety item scores of
      the Hamilton Depression Rating Scale were significantly higher in those with an
      early onset, but otherwise symptoms differed little. Heritability was greater in
      the early-onset group. There was a striking association of vascular disease
      and/or risk with late-onset patients. CONCLUSIONS: Vascular disease is associated
      with late-onset depression. This is consistent with the hypothesis that
      depression in later life is a more 'biological' disorder.

PMID- 8564323
TI  - Long-term effects of cognitive-behavioural therapy and lithium therapy on
      depression in the elderly.
AB  - BACKGROUND: We examine the effects of cognitive-behavioural therapy (CBT) as an
      adjuvant to acute physical treatment and lithium maintenance therapy in reducing
      depression severity over a follow-up year in elderly depressed patients. METHOD:
      The study consists of three phases. During the acute treatment and continuation
      phase, 17 of 31 patients received CBT as an adjuvant to treatment as usual.
      During the maintenance phase of 1 year, subjects were entered into a double
      blind, placebo-controlled study of low-dose lithium therapy. RESULTS: Receiving
      adjuvant CBT significantly reduced patients' scores on the Hamilton Rating Scale
      for Depression during the follow-up year (repeated measures analyses of variance;
      P = 0.007). No significant differences were found between lithium and placebo
      maintenance therapy. CONCLUSIONS: CBT can be adapted as an adjuvant therapy in
      the treatment of severely depressed elderly patients and reduces depression
      severity during follow-up. The prophylactic failure of long-term lithium therapy
      may be explained through poor compliance.

PMID- 8564324
TI  - Further evidence that reading ability is not preserved in Alzheimer's disease.
AB  - BACKGROUND: Pre-morbid intelligence level is routinely assessed in Alzheimer's
      disease using the National Adult Reading Test (NART). This practice is based on
      the assumption that pronunciation of irregular words remains unaffected by the
      disease process. Recent reports have suggested that reading ability may become
      compromised in moderately demented subjects. METHOD: Sixty-eight probably
      Alzheimer patients were classified into stages of severity (minimal, mild and
      moderate) using the Mini-Mental State Examination (MMSE). NART and demographic
      equations were used to estimate pre-morbid ability. RESULTS: A significant
      correlation emerged between dementia severity and reading ability, NART v. MMSE
      scores, r = 0.46, P < 0.01. When the total sample was subdivided into moderate,
      mild and minimal subgroups, significant between-group differences emerged,
      despite the groups being well matched for age, sex, and years of full-time
      education. Pre-morbid IQ, as estimated by demographic regression equations, did
      not correlate with dementia severity. CONCLUSION: NART performance is compromised
      in moderate Alzheimer disease, and the measure provides a serious underestimate
      of pre-morbid IQ in patients with an MMSE of 13 or less.

PMID- 8564325
TI  - Psychiatric symptoms associated with dementia in older people with learning
      disability.
AB  - BACKGROUND: This paper describes a study of non-cognitive features of dementia in
      a population of 105 people over 50 years of age, with learning disability.
      METHOD: The study involved psychiatric assessment using the Psychiatric
      Assessment Schedule for Adults with a Developmental Disability (PAS-ADD), a semi
      structured psychiatric interview developed specifically for people who have
      learning disability. Dementia was diagnosed using a combination of informant
      interviewing and observation of cognitive change over a three year period.
      RESULTS: Sample members with definite dementia had higher levels of sleep
      difficulty, hypersomnia, irritability, inefficient thought, loss of interest and
      anhedonia. Discriminant function analysis showed that non-cognitive features
      could help discriminate between definite and probable cases. CONCLUSIONS: Results
      support the previously reported observation for the general population that
      cognitive and non-cognitive features are only weakly related. The study suggests
      that psychiatric symptom information may be useful in screening for dementia in
      people with learning disability.

PMID- 8564326
TI  - Morbid jealousy in alcoholism.
AB  - BACKGROUND: Morbid jealousy is an incompletely understood syndrome. The
      association between morbid jealousy and alcoholism is unclear. METHOD: Morbid
      jealousy was assessed in 207 male patients with alcohol dependence (DSM-III-R)
      using a semi-structured interview schedule administered both to patients and
      their spouses. RESULTS: Thirty-four per cent (71 out of 207) suffered from morbid
      jealousy. Morbid jealousy had different manifestations. Some patients expressed
      it only when intoxicated, others even when sober and in some the jealousy took
      the form of a delusional disorder. CONCLUSIONS: Alcoholism appears to have an
      aetiological role in the development of morbid jealousy. Detecting morbid
      jealousy when it is expressed only under the influence of alcohol has preventive
      implications.

PMID- 8564327
TI  - Family functioning in adolescent anorexia nervosa.
AB  - BACKGROUND: Difficulties in family functioning have been noted since early
      descriptions of anorexia nervosa and may be of importance aetiologically.
      Previous studies have a number of methodological problems. METHOD: Thirty-five
      anorexic adolescents were age/sex matched with psychiatric and community
      controls. A diagnostic interview and a questionnaire, the Family Assessment
      Device (FAD) were administered to control subjects and their mothers. Anorexic
      families only received the McMaster Structured Interview of Family Functioning.
      RESULTS: Multivariate analyses of FAD scores showed pathological ratings for
      psychiatric control but not anorexic families, compared with community controls.
      By contrast objective ratings revealed marked dysfunction in anorexic families
      (greater in the purging subgroup). CONCLUSION: Family functioning in anorexic
      families is normal by self-report but not by an objective measure. Anorexic
      families in the purging subgroup appear most dysfunctional.

PMID- 8564328
TI  - The significance of a history of childhood sexual abuse in bulimia nervosa.
AB  - BACKGROUND: Childhood sexual abuse (CSA) is found to have occurred to a
      substantial minority of women with bulimia nervosa. Its clinical significance is
      unclear. METHOD: We studied 87 bulimic women in a clinical trial. Structured
      interviews determined the presence of CSA, DSM-III-R disorders, global
      functioning, and depressive and bulimic symptoms. RESULTS: Forty-four per cent
      reported a history of CSA. Bulimic women with CSA reported earlier onset of
      bulimia, greater depressive symptoms, worse global functioning and more suicide
      attempts, and were more likely to meet criteria for bipolar II disorder, alcohol
      and drug dependence, conduct disorder and avoidant personality disorder.
      CONCLUSIONS: Although those with CSA had greater comorbidity, it was not an
      important modifier of bulimic symptoms.

PMID- 8564329
TI  - The use of statistics in the British Journal of Psychiatry.
AB  - BACKGROUND: Statistical error rates in the medical literature are generally high.
      METHOD: All papers published in the British Journal of Psychiatry in 1993 which
      presented numerical results were reviewed by the author for statistical errors.
      RESULTS: A total of 248 papers were published, of which 164 (66%) presented
      numerical results. Sixty-five (40% of 164) papers contained statistical errors.
      Many errors were not serious in nature, but some were serious enough to cast
      doubt on conclusions. The error rates are similar to those found in an earlier
      study. CONCLUSIONS: The statistical error rate is unacceptably high. There is no
      evidence of a change in the statistical error rate over time.

PMID- 8564330
TI  - Improving the quality of statistics in psychiatric research.

PMID- 8564331
TI  - A "PC" model of the mind.

PMID- 8564332
TI  - A "PC" model of the mind.

PMID- 8564333
TI  - A "PC" model of the mind.

PMID- 8564334
TI  - Lead-in placebo washout period.

PMID- 8564335
TI  - Obstetric complications in schizophrenia.

PMID- 8564336
TI  - Obstetric complications in schizophrenia.

PMID- 8564337
TI  - Eugenics.

PMID- 8564338
TI  - Mania precipitated by carbamazepine withdrawal.

PMID- 8564339
TI  - Laryngeal dystonia.

PMID- 8564340
TI  - Risperidone response after no clozapine response.

PMID- 8564341
TI  - Fungal infections in cancer patients: any progress?

PMID- 8564342
TI  - Hospice--a homecare service for terminally ill cancer patients in southern
      Switzerland.
AB  - We describe the circumstances that led to the building up of a home care service
      for terminally ill cancer patients in a part of southern Switzerland. We describe
      the goals, the structure and the functioning of this service as it works in two
      areas. We give some results of a retrospective study on hospitalization, home
      care and death at home.

PMID- 8564343
TI  - Prevention and therapy of fungal infections in cancer patients. A review of
      recently published information.
AB  - This review of recent publications in the field of fungal infections in cancer
      patients clearly confirms that protracted severe granulocytopenia is a major risk
      factor for their development. Because severe and prolonged granulocytopenia plays
      such a major predisposing role for fungal infections, it is likely that the use
      of the colony-stimulating factors, which are able to reduce the duration and the
      severity of granulocytopenia, might prove effective in decreasing the frequency
      and the severity of these infections. Another conclusion is that certain
      categories of patients with granulocytopenia might benefit from antifungal
      prophylaxis and empiric therapy. Conversely, there are other populations who will
      benefit only marginally from such strategies. Imidazoles, namely fluconazole, for
      the prevention of local and systemic Candida infections have been shown to be
      effective in granulocytopenic patients. So far, the development of resistance has
      not been a major problem. In patients at the greatest risk of developing severe
      fungal infections, such as those receiving high-dose corticosteroid therapy for
      GVHD after allogeneic bone marrow transplantation, early administration of low
      doses of amphotericin B seems to be effective in reducing the development of
      systemic fungal infection. In terms of therapy, amphotericin B is still the
      standard approach, especially for empiric treatment, prior to the recognition of
      a specific pathogen.

PMID- 8564344
TI  - The role of ECG monitoring during bronchoscopy in lung cancer patients.
AB  - Bronchoscopy, as an endoscopic technique, is associated with respiratory and
      circulatory disorders. Cardiac rhythm disorders are the most common
      cardiovascular complications of bronchoscopy. In order to study ECG changes
      during bronchological procedures, ECG monitoring was undertaken (30 min before,
      during and 30 min after bronchoscopy) in 100 patients, 76 with bronchial
      carcinoma and 24 suffering from some other pulmonary disease. Within the same
      intervals PaO2, PaCO2 and pH were recorded. All recorded arrhythmias were
      classified as minor and major. According to arrythmia noted during bronchoscopy,
      patients were divided into two groups: group 1 comprised 70 patients without
      arrythmia or with minor arrythmia (70%) and group 2, 30 patients with major
      arrythmia (30%). No significant difference was noted in associated cardiac
      disease, cardiological medication, blood pressure, pulse rat, PaO2, PaCO2 and pH
      (P < 0.05). The only statistically significant difference between the two groups
      of patients was related to localization of tumour in the lungs. We could not
      correlate the occurrence of major arrythmia during bronchoscopy in patients with
      lung carcinoma with any underlying cardiopulmonary condition. Significant
      differences were noted in effects of tumour localization, i.e. major arrhythmias
      are more common and more dangerous in cases of tumours of the left bronchial
      trunk (possible bronchoscopic stimulation of the left stellate ganglion), and we
      therefore believe that ECG monitoring is desirable in these cases for the early
      detection and appropriate management of haemodynamically dangerous arrhythmias.

PMID- 8564345
TI  - Postoperative infections in immunocompromised patients after oncological surgery.
AB  - Immunodeficiency secondary to cancer chemotherapy (chemotherapy for less than 3
      months, or intensive chemotherapy with bone marrow transplant) may be responsible
      for postoperative infections. To estimate the value of this hypothesis, a
      prospective study was done over a period of 18 months in patients who had
      undergone pulmonary surgery. Antibiotic prophylaxis was by pefloxacin, one tablet
      (400 mg) 1 h before surgery then 11 h after. Clinical examination, a chest X-ray
      and blood cell count were carried out every day for 10 days and on the 15th day.
      All the drain-tips were cultured. In a case of infection, samples were obtained
      and cultured. One group comprised 22 immunodeficient patients (group A), and 33
      patients (group B) had received no prior chemotherapy (bone-marrow
      transplantation = 36.7%). There were differences between the two groups in age
      (A:33.5 +/- 12.3 years; B:50.8 +/- 18.4 years), and type of tumour (A: metastasis
      = 95.5%; B: lung cancer = 51.5%). Surgical operation was bilateral for 36.4% of
      the patients in group A. There was more anatomical resection (pneumonectomy and
      lobectomy) in group B. Lung function did not differ between the two groups
      (abnormalities: A = 54.6%; B = 63.6%). In group A, there were 3 pulmonary
      infections (13.7%), but in group B 10 infections (30.3%) with 9 pulmonary
      infections (4 with bacteraemia) and 1 wound infection. The bacteriological
      finding showed two pathogens in 7 cases and no bacteriological isolates in 2
      cases. With broad-spectrum antibiotherapy all the patients were cured except 1.
      There was one postoperative death in group B. This patient died of respiratory
      distress after pneumonectomy complicated by pneumonia and septicaemia
      (Streptococcus pneumoniae) in the remaining lung. Surgical procedures are
      performed with increasing frequency on patients with immunocompromised status.
      Classically the risk of infection is more important for these patients. In this
      study prior cancer chemotherapy or bone marrow transplantation did not seem to be
      an aggravating factor of the risk of infection. But further methodological
      analysis would not allow us to distinguish between a real impact of chemotherapy
      and the influence of group heterogeneity.

PMID- 8564346
TI  - Nature and outcome of febrile episodes in patients with pancreatic and
      hepatobiliary cancer.
AB  - Fifty febrile episodes in patients with hepatobiliary and pancreatic cancer were
      reviewed. Biliary obstruction often resulting in cholangitis was an important
      predisposing factor, whereas neutropenia (< 500 PMN/mm3) was uncommon (10%).
      Microbiologically documented infections originating from the gastrointestinal
      tract were predominant, with Enterococcus faecalis and Escherichia coli being
      isolated most often. Non-infectious causes of fever occurred in 16% of patients.
      Only one patient developed a fungal infection. The overall response rate to
      therapy was 94%, with 32% being eligible for outpatient management. These data
      are quite different from those generated from patients with hematologic
      malignancies and indicate that disease-site specific management guidelines need
      to be developed for febrile episodes in patients with various underlying
      neoplasms.

PMID- 8564347
TI  - Endoscopic management of acute respiratory failure related to tracheobronchial
      malignancies.
AB  - Endobronchial treatment has an expanding role in the treatment of
      tracheobronchial tumors. Most patients are treated in this way for the palliation
      of dyspnea caused by a tumor located in a major airway. In cases where immediate
      relief is required, prompt control is better achieved by the neodymium-YAG laser
      or by stents. These two modalities and their indications and limitations in the
      endoscopic management of acute respiratory failure related to tracheobronchial
      malignancies are discussed.

PMID- 8564348
TI  - Treatment of tumour-induced hypercalcaemia in advanced breast cancer patients
      with three different doses of disodium pamidronate adapted to the initial level
      of calcaemia.
AB  - A group of 38 female patients with advanced breast cancer experiencing the first
      occurrence of tumour-induced hypercalcaemia (TIH), mostly with osteolytic
      progressive bone metastases, were included in a prospective calcaemia-adapted
      study using three different doses of pamidronate (30 mg, 45 mg and 60 mg). Serum
      calcium normalisation was achieved in 29/38 (76%) patients. Comparison of the
      response rate in three therapeutic groups confirmed the need for higher doses of
      pamidronate in moderate TIH. Our study also emphasised the importance of
      effective anticancer systemic therapy.

PMID- 8564349
TI  - Nosocomial bacterial and fungal meningitis in cancer patients.
AB  - Five cases of nosocomial meningitis are described that occurred within 5 years in
      a national cancer center in neutropenic cancer patients after cytotoxic
      chemotherapy: one caused by the yeast Aureobasidium mansoni and four caused by
      bacteria (two by Enterococcus faecalis and one by Salmonella enteritis and
      Arcanobacterium haemolyticus. Despite the severe symptoms, all cases were cured
      with appropriate antimicrobial therapy.

PMID- 8564350
TI  - Breast forms after mastectomy--patient's issues.
AB  - After mastectomy restoration of body symmetry, a very important aspect of coping
      with daily life, may be achieved either using breast forms that are suspended in
      a brassiere or by a new system in which breast forms are attached by adhesive
      strips to the thorax walls. The system promises free and easy movement,
      favourable effects on lymphoedema, and improvements with respect to dressing.
      Brassieres are not necessarily needed. The influence of improved prosthetics on
      patients' self concept and well-being was investigated. A group of 67 patients
      after unilateral mastectomy tested custom breast forms and self-adhesive breast
      forms. Using the Frankfurter Selbstkonzeptionsskalen (Frankfurt Self-Concept
      Scales), plus additional questions concerning problems after mastectomy, self
      concept was assessed before study and after 3 months. Analysis of variance with
      repeated measures revealed significant differences with respect to the scale
      Social Contact and Relations (FSKU). Most patients were better satisfied with
      epicutaneous self-adhesive breast forms. The weight and type of movement of the
      self-adhesive breast forms were considered natural, and adhesive strips were well
      tolerated. A total of 78% were able to wear more fashionable clothing. Breast
      reconstruction became less important for 62%. The new concept of self-adhesive
      breast forms is an improvement with respect to social and pyschological
      rehabilitation.

PMID- 8564351
TI  - A rare complication of implanted central-venous access devices: catheter fracture
      and embolization.
AB  - Totally implanted central-venous access devices are frequently used for the
      administration of chemotherapy or parenteral nutrition. Catheter fracture is a
      rare complication of these devices, with an estimated rate of 0.1%. We have
      lately seen three cases of catheter fracture with embolization of a catheter
      fragment to the heart and pulmonary vessels. These cases are described in this
      article. Catheter fracture is caused by intermittent compression of the catheter
      between the clavicula and the first rib, which can occur when the catheter has
      been inserted too far medially. When, on an X-ray of the chest, the catheter is
      shown to be compressed at the point where the clavicula crosses the first rib, or
      when infusion through the device suddenly becomes difficult, the chance of
      catheter fracture is high and the device should be removed.

PMID- 8564353
TI  - Prions of yeast and heat-shock protein 104: 'coprion' and cure.

PMID- 8564352
TI  - Granisetron (Kytril): a survey of use in clinical practice in Switzerland.
AB  - Data on the use of intravenous grainsetron (Kytril) were collected during a
      surveillance exercise amongst Swiss oncologists. The data were analysed to
      ascertain how grainsetron was used, and to document the incidence of adverse
      experiences in a clinical setting. Forty-nine oncologists at 40 Swiss centres
      were surveyed for their use of granisetron for the prevention and treatment of
      chemotherapy-induced nausea and vomiting. All were advised to follow the Swiss
      prescribing instructions for granisetron. They were invited to return data on
      patient demography, chemotherapy duration, granisetron dosing and adverse
      experiences. From 285 patients it was deduced that the mean daily dose of
      granisetron was 1.3 ampoules (3.9 mg) and the median daily dose was 1 ampoule (3
      mg). The average number of doses of granisetron per patient per session was 3.8.
      There were 44 reports of adverse experiences by 34 patients, the most common
      report being headache. The survey confirmed that the large majority of patients
      undergoing chemotherapy required only a single dose of granisetron per day, and
      that the adverse experience profile was good.

PMID- 8564354
TI  - What makes nodulation signals host-plant specific?

PMID- 8564355
TI  - The varied lifestyles of intracellular pathogens within eukaryotic vacuolar
      compartments.
AB  - Many bacterial pathogens and eukaryotic parasites can enter mammalian cells and
      live intracellularly inside membrane-bound vacuoles. The intravacuolar lifestyle
      of these pathogens plays a key role in pathogenesis. Understanding the molecular
      basis of the development of these specialized intracellular compartments is
      critical to understanding how these organisms cause disease.

PMID- 8564356
TI  - Role of O-antigen variation in the immune response.
AB  - The O antigen is an extremely variable surface polysaccharide of Gram-negative
      bacteria. This variation is thought to allow the various clones of a species each
      to present a surface that offers a selective advantage in the niche occupied by
      that clone. The interactions between O antigen and the immune system are central
      to determining the selective advantage of each clone.

PMID- 8564357
TI  - Long-term survivors of HIV-1 infection.
AB  - The clinical course and outcome of HIV-1 infection are highly variable. A full
      spectrum of pathology has been observed, from rapid progression to AIDS within
      months of HIV-1 seroconversion, to asymptomatic survival for more than a decade.
      This phenomenon probably reflects the multiphasic and multifactorial nature of
      the virus-host interactions. Obviously, interest in the extremes now recognized
      in HIV-1 disease progression is growing, with the hope that mechanisms of
      protection may be found.

PMID- 8564358
TI  - Heat-shock proteins in host-pathogen interactions: implications for cystic
      fibrosis.
AB  - The expression of heat-shock proteins by both pathogen and host cells during the
      phagocytosis of Staphylococcus aureus and Pseudomonas aeruginosa, two bacterial
      species that colonize the airways of patients with cystic fibrosis, probably
      contributes to pulmonary inflammation in cystic fibrosis. Here, we discuss the
      likely signals for heat-shock-protein induction within host and bacterial cells.

PMID- 8564359
TI  - BCG vaccination against tuberculosis: past disappointments and future hopes.
AB  - Three billion doses of the bacille Calmette-Guerin (BCG) vaccine have been given
      over the past 60 years. BCG has a widely variable ability to protect humans
      against tuberculosis. This article examines some of the reasons for this
      variability, and discusses ways in which BCG vaccination might be improved.

PMID- 8564360
TI  - Prospects for new vaccines against tuberculosis.
AB  - The spectacular failure of the existing bacille Calmette-Guerin (BCG) vaccine in
      recent tuberculosis-control trials has prompted a search for potential
      replacements. Imaginative approaches currently under development include the
      modulation of BCG by the production of auxotrophic mutants or cytokine-secreting
      recombinants, and the development of subunit vaccines based on the major proteins
      of Mycobacterium tuberculosis.

PMID- 8564361
TI  - Are bacterial proteinases pathogenic factors?
AB  - Evidence is rapidly accumulating that suggests that the growth and proliferation
      of pathogenic bacteria depend on proteolytic enzymes of the invading organism and
      of the host. Proteinase inhibitors targeting bacterial proteinases may be useful
      antimicrobial agents.

PMID- 8564362
TI  - Mutual adaptation of bacteriophage fd, pfd plasmids and their host strains.
AB  - The synthetic plasmid pfdC1 with the replication origin of phage fd and fd gene 2
      grows autonomously in E. coli cells. DNA sequencing revealed several mutations
      compared to the fd genome causing reduced expression of viral gene 2 protein,
      which can be toxic for the host cell. Another adaptation was noticed for E. coli
      strains with a copy of fd gene 2 on the F-episome and a pfdA-plasmid with a
      minimal fd replication origin, when maintained at 42 degrees C. The carrier cells
      adjusted their cellular metabolism to these stress conditions, whereas
      replication functions of the plasmid or expression of fd gene 2 on the F-episome
      were not changed. The filamentous bacteriophages tend to reduce their genome size
      into miniphages, which was also observed for phages with an antibiotic resistance
      gene. Bacteriophages with a transposon insertion in the viral gene 2 had a
      tendency to restore the mutated gene by exchange with the functional gene 2
      carried in recA-host cells. Mobilization of pfd-plasmids with RP4 transfer
      functions was reduced due to interference of replication and transfer in the
      rolling circle mode. The vectors used in these studies can also be applied as
      cloning vectors, which are compatible with many other plasmid vectors.

PMID- 8564363
TI  - Molecular analysis of the molybdate uptake operon, modABCD, of Escherichia coli
      and modR, a regulatory gene.
AB  - The nucleotide sequence of a 6.8-kb chromosomal subfragment of plasmid pHW100
      complementing an Escherichia coli modC (chlD) mutant has been determined. This
      DNA region encodes the genes of a high-affinity uptake system for molybdate
      arranged in an operon with the genes modABCD. Since the modA product has a signal
      peptide at the N-terminus it probably is the periplasmic binding-protein for
      molybdate. The products of modB (chlJ) and modC (chlD) have been described
      earlier as the inner membrane protein and the ATP-binding protein of the
      molybdate transport system, respectively. At present, there is no information on
      possible functions of the fourth gene of the operon, modD. Upstream of the mod
      operon, two other gene loci, termed modR and an open reading frame ORF6 could be
      identified. ModR shares homology with a molybdenum-pterin binding protein of
      Clostridium pasteurianum. ORF6 has extensive homology to ModC and other
      nucleotide-binding proteins of E. coli. Insertional inactivation of modR and ORF6
      using a gentamicin resistance gene cartridge has no effect on molybdoenzyme
      activities, indicating that none of the two gene products is essential for
      molybdate uptake or molybdenum cofactor synthesis. However, by using a plasmid
      carrying a modA-lacZ gene fusion we observed that inactivation of modR releases
      repression of the mod operon independent of the molybdate concentration in the
      medium. This indicates that modR is a component of the mod operon regulation or
      the repressor itself.

PMID- 8564364
TI  - PCR-fingerprinting used for comparison of ex type strains of Trichoderma species
      deposited in different culture collections.
AB  - PCR-fingerprinting with primers (GACA)4, (GTG)5, M13 (core sequence of phage
      M13), and OPB-05 was used to compare ex type strains of various species of
      Trichoderma. The ex type strain of each species was obtained from different
      culture collections. PCR-fingerprints of each ex type culture, despite of
      separate cultivation over a long period of time (sometimes decades) by different
      culture collections, were identical. Ex type strains could be discriminated from
      a number of other strains belonging to the same species, since every strain was
      characterized by its individual PCR-fingerprint. PCR-fingerprinting is
      recommended as a basic tool for proving the identity of strains, especially with
      regard to comprehensive culture collections. Investigations of Trichoderma
      todica, a species of undefined systematic position within the genus Trichoderma,
      suggest a close relationship to Trichoderma paraceramosum. Morphological and
      molecular data indicate that Trichoderma todica and Trichoderma parceramosum are
      conspecific.

PMID- 8564365
TI  - The combination of Gilbert/Maxam chemical sequencing and the dideoxynucleotide
      chain termination approach facilitates the construction of species specific PCR
      primers based on diagnostic RAPD bands.
AB  - The randomly amplified polymorphic DNA technique (RAPD) is a modification of PCR
      that uses short, arbitrarily generated single primers to amplify genomic DNA.
      Amplified DNA-fragments are often polymorphic and can be used as individual,
      population- or species-specific markers. Because the RAPD technique requires a
      very high degree of reproducibility at the instrumentation level and with regard
      to buffer conditions, we propose to synthesize highly specific conventional PCR
      primers, the sequence of which is based on the primary diagnostic RAPD bands. In
      this communication we present a fast and convenient experimental strategy for
      converting the non-stringent RAPD conditions with their low annealing
      temperatures to stringent PCR conditions. Diagnostic RAPD bands were sequenced by
      a combination of chemical (Gilbert/Maxam) and chain termination (Sanger)
      techniques. Based on this sequence information, highly specific oligonucleotide
      primers were synthesized. The value of this approach was demonstrated for the
      molecular diagnosis of the important rape seed (Brassica napus) pathogen
      Leptosphaeria maculans.

PMID- 8564366
TI  - Application of the PCR technique to detect Phytophthora infestans in potato
      tubers and leaves.
AB  - A characterized repetitive sequence from Phytophthora infestans (P. infestans)
      was used to perform a PCR with the DNA from the four races 1, 3, 4, and 1-11. To
      obtain amplifiable DNA, all extractions had to be purified by DNA adsorbing spin
      columns. Only two out of four tested primers were well suited and gave an DNA
      amplificate of the same size for all four races. After optimization the detection
      limit of the PCR corresponded to 100 ng of freeze-dried mycelia per ml,
      specificity was established when testing a collection of the most important
      potato pathogenic fungi and bacteria. Using P. infestans zoospores to infect
      tuber slices, the detection threshold was determined to be two days post
      infection when 3 to 6 zoospores were applied. After infiltrating the tenfold
      concentration into potato leaves a visible PCR signal was obtained one day post
      infection. Further improvements of the sensitivity threshold in detecting P.
      infestans for breeding and prognosis purposes are discussed.

PMID- 8564367
TI  - Drug resistant bacteria in non carbonated mineral waters.
AB  - The presence of antibiotic resistant bacteria was revealed among bacteria
      isolated from non carbonated mineral waters bottled in plastic (PVC) and in glass
      containers. Heterotrophic plate count values ranged between < 10 and 4.3 x 10(3)
      and between < 10 and 1.2 x 10(4) colony forming units/ml for the waters bottled
      in PVC and glass, respectively. The greatest resistance to a single antibiotic,
      39.1% of 320 isolates from mineral waters, was found for nalidixic acid.
      Resistance to the other antibiotics was as follows: ampicillin (26.2%),
      bacitracin (19.7%), cotrimoxazole (18.7%), streptomycin (15.0%), tetracycline
      (14.4%), gentamycin (11.6%), chloramphenicol and rifampin (9.7%). The strains
      resistant to two or more antibiotics (multiple antibiotic resistant, MAR)
      provided 51% of the total isolates. Identification of 127 MAR strains showed that
      in the mineral waters gram-positive cocci dominated. The second, third and fourth
      group of identified MAR phenotypes were, in order to importance, gram-negative
      non-fermentative rods, gram-positive rods and gram-negative fermentative rods.
      The importance of the antibiotic resistant bacteria in mineral water is
      discussed.

PMID- 8564368
TI  - L-alanine: 4,5-dioxovalerate transaminase in Leishmania donovani that differs
      from mammalian enzyme.
AB  - Leishmania protozoans are the causative agents of leishmaniasis, a major
      parasitic disease in humans. The parasites manifest a nutritional requirement for
      heme compounds since they are deficient in heme biosynthesis. In this study we
      have demonstrated for the first time the presence of the enzyme L-alanine: 4,5
      dioxovalerate transaminase in Leishmania donovani. This enzyme catalyzes the
      synthesis of 5-aminolevulinic acid (ALA), the first committed step in heme
      synthesis. Thus the defect in heme biosynthesis pathway in Leishmania must lie at
      some enzymatic level subsequent to synthesis of ALA. The enzyme was found to be
      present in both virulent and avirulent strains of L. donovani. The virulent
      promastigotes showed a 41% higher specific activity as compared to the avirulent
      strain. The enzyme activity was found to be inhibited in the presence of heme and
      methylglyoxal. Immunoblot analysis revealed that L-alanine: 4,5-dioxovalerate
      transaminase in L. donovani was immunologically different from that in mammals.

PMID- 8564369
TI  - Comparative larvicidal activities of the four Bacillus thuringiensis serovars
      against a chironomid midge, Paratanytarsus grimmii (Diptera: Chironomidae).
AB  - The four reference strains of Bacillus thuringiensis, known to be pathogenic for
      mosquito larvae of the family Culicidae (Diptera), were examined for their
      larvicidal activities against a chironomid species, Paratanytarsus grimmii
      (Diptera: Chironomidae). Of the four, the type strain of B. thuringiensis serovar
      israelensis (H14) exhibited the highest activity against both early- and late
      instar larvae, while the type strain of serovar kyushuensis (H11ac) and the
      strain 73-E-10-2 (H10, serovar darmstadiensis) showed relatively moderate
      toxicities. The strain HD-1 of serovar kurstaki (H3abc) had no larvicidal
      activity on this chironomid midge.

PMID- 8564370
TI  - Colonization factors of enterotoxigenic E. coli (ETEC) from residents of northern
      Egypt.
AB  - Infection caused by enterotoxigenic Escherichia coli (ETEC) poses a serious
      health problem to children in developing countries. Colonization of the small
      intestinal mucosa by ETEC strains is mediated by antigenically specific fimbriae,
      also known as colonization factor antigens (CFA). The importance of this study
      arises from reports that active and passive immunization with ETEC strains
      harboring CFAs induced protective immunity against diarrhea in animal models with
      preformed antibodies. In humans, ETEC containing CFA/I, II, III and IV have been
      identified. The aim of this study was to define CFAs of ETEC isolated in
      Alexandria, Egypt. One hundred and seven ETEC isolates from 132 human residents
      in Alexandria, Egypt were isolated during a birth cohort study. ETEC isolates
      were screened for heat labile (LT) and heat stable (ST) toxins using a 32P
      oligonucleotide hybridization probe and a GM1 ELISA. These isolates were examined
      using monoclonal antibodies against CFA/I, II, III, IV, and against the putative
      colonization antigens PCF0159 and PCF0166, CS 7 and CS 17. CFAs were found in 48%
      of ETEC strains. CFA/I was found in 18% of the strains, CFA/II in 10% and CFA/IV
      in 14%. CFA III was not found. All fifteen strains expressing CFA/IV expressed
      CS6 and produced ST. CFA/IV was not found in non-ST producing strains, while
      CFA/I was absent in ST-only producing strains.

PMID- 8564371
TI  - A survey of aflatoxins and aflatoxigenic Aspergillus flavus in corn-based
      products from the Spanish market.
AB  - The natural occurrence of aflatoxins B1, B2, G1 and G2, incidence of Aspergillus
      flavus, and capacity to produce aflatoxins by A. flavus isolates, were
      investigated in 100 corn-based samples from Spain destined for human and animal
      consumption. Only one sample for animal consumption and none for human
      consumption were found to be contaminated with aflatoxins B1 and B2. The levels
      of contamination were 0.15 micrograms/g of B1 and 0.08 micrograms/g of B2. Of 43
      isolate of A. flavus, only 4 were aflatoxin producers.

PMID- 8564373
TI  - Role of preoperative and postoperative sensorimotor training on restoration of
      the equilibrium behavior in adult mice following cerebellectomy.
AB  - The equilibrium behavior of cerebellectomized C57/BL6 adult mice was studied on a
      rota rod rotating at 20 revolutions per minute and the influence of preoperative
      or/and postoperative training on restoration of equilibrium capabilities
      investigated. The duration of the preoperative training was either short (1 day)
      or long (7 days). The postoperative training began either the day after
      cerebellectomy or was delayed by 7 days. The results demonstrate that
      postoperative training was efficient in restoring the equilibrium behavior in all
      cases, except for the animals which were trained for a long period (7 days)
      before the lesion. Preoperative training was also efficient providing it was long
      enough (7 days), except for the animals which postoperative training began the
      day after cerebellectomy. It can be stated that both preoperative and
      postoperative trainings influence the restoration of the equilibrium following a
      cerebellectomy and that, in some instances, preoperative training can be as
      efficient as postoperative.

PMID- 8564372
TI  - Scopolamine selectively disrupts the acquisition of contextual fear conditioning
      in rats.
AB  - Muscarinic cholinergic antagonism produces learning and memory deficits in a
      variety of hippocampal-dependent tasks. Hippocampal lesions produce both
      acquisition deficits and retrograde amnesia for contextual fear conditioning, but
      do not impact fear conditioning to discrete cues. In order to examine the effects
      of muscarinic antagonism in this paradigm, rats were given scopolamine (1 mg/kg)
      either before or for 3 days after a Pavlovian fear-conditioning session in which
      tones were paired with aversive footshocks. Fear to the context and the tone was
      assessed by measuring freezing in separate tests. It ws found that pretraining,
      but not posttraining, scopolamine severely impaired contextual fear conditioning;
      tone conditioning was not affected under either condition (cf., Young, Bohenek, &
      Fanselow, Neurobiology of Learning and Memory, 63, 174-180, 1995).

PMID- 8564374
TI  - Effects of unilateral entorhinal cortex lesion and ganglioside GM1 treatment on
      performance in a novel water maze task.
AB  - Transient deficits have been reported after unilateral entorhinal cortex (EC)
      lesion. To determine whether there is a more persistent deficit, adult male
      Sprague-Dawley rats with electrolytic or sham lesions of the left entorhinal
      cortex were examined on acquisition of a modified working memory task in the
      Morris water maze. This delayed matching-to-sample task, with a 1-h intertrial
      interval, reveals a significant deficit in total distance to platform in both
      presentation (Trial 1) and matching (Trial 2) in the rats with entorhinal
      lesions. We have also found that this test can be used to assess significant
      deficits in perseveration (repeated nonproductive movement) in rats with
      entorhinal lesions. The deficits can be seen up to 16 days postinjury.
      Administration of ganglioside GM1 resulted in a moderate improvement in
      performance in both water maze measures analyzed. All groups (sham operated,
      lesion with saline treatment, and lesion with ganglioside GM1 treatment) were
      given three other tests, which were used to evaluate possible contributing
      factors to deficient water maze performance. A one-trial test for exploration of
      novel objects revealed no significant, simple working memory deficit in any
      group. Plus maze testing, to assess possible differences in levels of anxiety or
      increased activity as a component of water maze performance, also revealed no
      differences in the three groups. All groups were also similar in motor activity,
      shown by monitoring of activity levels. The worsened water maze performance
      observed in rats with EC lesion may be related to deficits in working memory
      ability within the framework of acquisition of a more complex spatial learning
      task.

PMID- 8564375
TI  - Effects of parafascicular electrical stimulation and lesion upon two-way active
      avoidance in rats.
AB  - To evaluate a possible role of the parafascicular nucleus (PF) in modulating
      distributed two-way active avoidance acquisition and long-term retention (LTR),
      we designed two experiments. Experiment I was aimed at checking whether
      posttraining PF intracranial electrical stimulation (PF ICS) can improve the
      acquisition and/or the LTR of the task. All subjects (Ss, male Wistar rats) were
      implanted with an electrode at the PF. After each learning session two groups of
      Ss were stimulated for 10 (ICS-10 group) and 5 (ICS-5 group) min, respectively. A
      Control group never received PF ICS, while Ss in an ICS-Control group received PF
      ICS only during a previous search for a nonconvulsive current intensity.
      Unexpectedly, the ICS-Control group showed poor performance of the task compared
      to the remaining groups. Since the histological analyses showed that the
      pretraining ICS treatment produced some PF tissue lesion, Experiment II was aimed
      at evaluating the effects upon the same task of (1) pretraining PF electrolytical
      lesions (PF-Lesion group) and (2) posttraining PF ICS treatment (ICS group) at a
      lower current intensity and without a previous search for nonconvulsive current
      intensity. PF pretraining lesion decreased conditioning, while posttraining PF
      ICS did not affect it. We concluded that PF could have a modulatory role in
      acquisition, and might also contribute to posttraining consolidation, of a
      distributed two-way active avoidance.

PMID- 8564376
TI  - Distinct profile of working memory errors following acute or chronic disruption
      of the cholinergic septohippocampal pathway.
AB  - The behavioral effects of two amnestic treatments (intraseptal chlordiazepoxide
      (CDP) and intraventricular AF64A) were examined in a delayed-nonmatch-to-sample
      radial-arm maze (DNMTS) paradigm. The types of errors induced by these treatments
      in this working memory task were assessed to determine how acute and chronic
      disruptions of the medial septum affect different phases of working memory
      (encoding, maintenance, retrieval). Rats were initially trained to perform the
      DNMTS task with a 1-h delay imposed between the training and the testing
      sessions. The first experiment demonstrated that intraseptal injection of 30
      nmoles of CDP did not produce state-dependent learning. Rats were injected
      immediately following training with CDP or artificial cerobrospinal fluid (CSF;
      drug vehicle) and then prior to testing with CDP or CSF. Injection of CDP
      immediately following training (CDP-CSF) impaired performance of the task
      regardless of whether CDP was also administered before the postdelay test (CDP
      CDP). Rats infused with CDP only before the postdelay test (CSF-CDP) exhibited a
      proactive deficit characterized by intact retention of the predelay information
      (i.e., arms entered prior to the delay) but impaired performance on the postdelay
      component (arms entered only after the delay). These data indicate: (i) that
      state dependency does not explain the working memory deficits induced by
      intraseptal CDP; (ii) that pretest CDP disrupts the storage and utilization of
      working memory for current arm selections. The second experiment examined the
      behavioral effects induced by a permanent disruption of the cholinergic
      septohippocampal pathway produced by icv injection of the cholinotoxin AF64A.
      Rats were initially trained on the DNMTS task and then bilaterally injected icv
      with either AF64A (2.5 nmoles/side) or CSF. AF64A-treated rats exhibited a
      significant impairment of performance compared to CSF-treated controls. In
      contrast to the impairment exhibited by CDP-treated rats in Experiment 1, the
      performance of AF64A-treated rats displayed a deficit in the
      maintenance/retrieval of information acquired during RAM training and an
      impairment in ability to store current spatial information in working memory to
      guide postdelay testing performance. These studies demonstrate that acute and
      chronic disruptions of the septohippocampal pathway produce distinct profiles of
      cognitive impairment that should help to reveal the behavioral and
      neurobiological characteristics of spatial memory.

PMID- 8564377
TI  - Memory for magnitude of reinforcement: dissociation between the amygdala and
      hippocampus.
AB  - Rats were trained on a successive delayed conditional discrimination task
      measuring memory for magnitude of reinforcement. In the study phase of the task,
      the rats were given one of two cereals. One cereal contained 25% sugar; the other
      50% sugar. One of the two cereals was always designated the positive stimulus and
      the other the negative stimulus. This study phase was followed by the test phase
      in which the rat was shown an object which covered a food well. If the rat was
      given the negative stimulus in the study phase of the trial, no food reward was
      placed beneath the object. Whenever the positive stimulus was presented a food
      reward was available beneath the object. Performance was measured as the latency
      to uncover the food well. After reaching criterion level, the rats were given
      amygdala, hippocampal, or control lesions. Amygdala-lesioned rats showed
      significant deficits in performance, whereas no long-term deficits were observed
      for the hippocampal-lesioned groups even at longer retention delays. In
      additional experiments, it was shown that amygdala-lesioned, like normal, rats
      had similar taste preferences. Finally, normal and hippocampal-, but not amygdala
      , lesioned rats transferred readily to different cereals containing 25% or 50%
      sugar. Thus, it appears that the amygdala, but not the hippocampus, plays a
      significant role in explicit data-based or working memory for affect information
      based on magnitude of reinforcement.

PMID- 8564378
TI  - Differential effects of Ketaset/Rompun anesthesia on hypothermia-induced
      retrograde amnesia and its recovery.
AB  - A nonbarbiturate anesthetic consisting of ketamine HCl (Ketaset) and xlyazine
      (Rompun) was administered to assess the effects of anesthesia on hypothermia
      induced retrograde amnesia in Long Evans hooded and Sprague-Dawley albino rats.
      Results from Experiment 1a indicate that this anesthetic does not attenuate
      retrograde amnesia, and the findings from Experiment 1b suggest that awakening
      from Ketaset/Rompun anesthesia at normal body temperature (following
      administration of deep body cooling) does not attenuate the resulting hypothermia
      induced retrograde amnesia. Experiment 2 demonstrated that various delays between
      training and hypothermia resulted in a temporal gradient that was the same for
      animals cooled while either conscious or under anesthesia. The results of
      Experiment 3 showed that rats made amnesic while under anesthesia did not recover
      the target memory if given a recooling treatment, but rats that were made amnesic
      while conscious did recover the memory with the same reminder treatment. These
      findings indicate that the conscious processing of stimuli associated with
      hypothermia treatment is not necessary in inducing hypothermia-induced retrograde
      amnesia, but that conscious processing is an important factor if the amnesia is
      to be recovered with a recooling treatment.

PMID- 8564379
TI  - Inhibitory avoidance training induces rapid and selective changes in 3[H]AMPA
      receptor binding in the rat hippocampal formation.
AB  - The AMPA receptor has been shown to participate in the synaptic mechanisms
      involved in certain forms of learning and memory. We have previously demonstrated
      that the posttraining infusion of 6-cyano-7-nitroquinoxaline-2,3-dione, an alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor blocker, into
      the dorsal hippocampus of rats, causes retrograde amnesia of an inhibitory
      avoidance training. Here, we report on the effect of this learning task on
      3[H]AMPA binding to frozen rat brain sections. By using a quantitative
      autoradiographic analysis, we were able to demonstrate that the binding of 3[H]
      AMPA was increased by 40-80% in the CA1, CA2, CA3, and dentate gyrus subregions
      of the hippocampal formation of rats trained in a step-down inhibitory avoidance
      paradigm, compared to naive, shocked, and free exploration controls. This effect
      was evident between 30 and 180 min after training, and it was mainly due to an
      increase in the density, but not in the affinity of binding sites. No alterations
      in 3[H]AMPA binding were observed either in those animals that received only the
      footshock (shocked group) or in animals that were submitted to 1 min of free
      exploration of the training box (free exploration group). In the rest of the
      brain regions, including the frontal cortex, entorhinal cortex, striatum,
      amygdala, cerebellum, and thalamus, the 3[H]AMPA binding remained unchanged. In
      addition, the binding of 3[H]muscimol and 3[H]-flunitrazepam to the
      GABAA/benzodiazepine receptor complex was unaltered in all the experimental
      groups. In conclusion, rats submitted to a one-trial inhibitory avoidance
      training showed a rapid, selective, and specific increase in 3[H]AMPA binding in
      the hippocampal formation. The present findings support the hypothesis that
      hippocampal AMPA receptors are involved in the neural mechanisms underlying
      certain forms of learning and memory.

PMID- 8564380
TI  - Sex differences in vulnerability to developmental spatial learning deficits
      induced by limited binge alcohol exposure in neonatal rats.
AB  - The two main objectives of this study were (1) to replicate previous findings
      that 6 days of binge-like exposure to alcohol during the neonatal brain growth
      spurt induces significant place learning deficits in juvenile rats and (2) to
      determine whether more limited (3-day) binge-like exposure during the neonatal
      period induces place learning deficits and whether the effects depend on the
      developmental timing of the exposure. Using artificial rearing methods and a
      split-litter experimental design, groups of male and female neonatal rats were
      given binge-like exposure to 4.5 g/kg/day of ethanol in milk formula either on
      Postnatal Days (PD) 4-6, PD 7-9, or PD 4-9, which yielded mean peak blood alcohol
      concentrations of 230-260 mg/dl. Controls included an artificially reared
      gastrostomy control group (GC) given an isocaloric milk formula diet on PD 4-9
      and a suckle control group reared normally by lactating dams. Acquisition of
      place learning in the Morris spatial navigation task was trained for 6
      consecutive days beginning on PD 26; a probe trial was given at the end of the
      sixth day. As expected, both males and females given alcohol on PD 4-9 had
      significant deficits in acquisition and probe trial performance relative to SC
      and GC groups. Males given the PD 7-9 exposure had significant place learning
      deficits which were as severe as with the full 6-day exposure. The PD 4-6
      exposure in males produced only a nonsignificant trend toward slower acquisition.
      Females were not significantly affected by either 3-day exposure. The latter
      phase of the neonatal brain growth spurt appears to constitute a sex-specific
      period of enhanced vulnerability to alcohol-induced developmental spatial
      learning deficits.

PMID- 8564381
TI  - omega-Conotoxin GVIA disrupts memory formation in the day-old chick.
AB  - Calcium channel antagonists have previously been shown to alleviate age
      associated reductions in memory acquisition and enhance retention for a number of
      different tasks. We have investigated the effects of pretraining injections of
      nifedipine, nimodipine, and amlodipine (L-type calcium channel antagonists) and
      omega-conotoxin GVIA (an N-type calcium channel antagonist) on passive avoidance
      and visual discrimination learning in day-old Ross 1 chunky chicks. None of the L
      type calcium channel antagonists at any time or dose tested caused amnesia for
      the passive avoidance task or enhanced weak learning, and nifedipine did not
      affect acquisition or retention of the visual discrimination task. However,
      pretraining bilateral intracerebral injections of 1.25 pmole/hemisphere omega
      conotoxin GVIA produced amnesia for the passive avoidance task in chicks tested
      30 min or 3 h after training. The same dose of omega-conotoxin GVIA significantly
      reduced the rate of acquisition of the visual discrimination task, but did not
      affect retention of the task when tested 30 min or 3 h after training. These data
      indicate that calcium uptake via presynaptic N-type omega-conotoxin-sensitive but
      not L-type dihydropyridine-sensitive calcium channels is necessary for memory
      formation in young chicks.

PMID- 8564382
TI  - Spatial location learning in mice with ibotenate lesions of entorhinal cortex or
      subiculum.
AB  - This study examined the effects of ibotenate lesions of either the entorhinal
      cortex (EC) or the subiculum (SUB) on the ability of mice to memorize a single
      spatial location (initial discrimination), and on their capacity to switch to a
      new location (transfer) following the initial learning in an eight-arm radial
      maze. Results indicated that mice with ibotenate lesions of the EC or SUB were
      impaired in postoperative acquisition of the spatial discrimination task, making
      more reference, but not working memory, errors and displaying fewer first correct
      response trials than sham-operated control mice. Furthermore, additional damage
      to the ventral hippocampus exacerbated the impairment of performance induced by
      lesions of the SUB alone. In addition, all mice, except for the combined lesion
      group, exhibited similar performance levels when they were trained to choose
      another arm of the maze that had not previously been baited (transfer). These
      findings suggest that both the EC and the SUB play important roles in spatial
      information processing in mice.

PMID- 8564383
TI  - Protection of sperm from isoimmune attack in vivo by pretreatment with antisperm
      Fab: fertility trials in the immune rabbit model.
AB  - We tested the hypothesis that binding of rabbit isoimmune antisperm Fab fragments
      to rabbit sperm prior to artificial insemination could protect the sperm from
      isoimmune attack in vivo and lead to normal pregnancy and healthy offspring in
      isoimmune does. Twenty-four female rabbits and 4 males were used. Twelve does
      were immunized with rabbit sperm to induce isoimmunity and 12 does immunized with
      adjuvant/saline served as controls. Following 5 immunizations, the immune serum
      IgG fraction and its Fab fragments were prepared. The does from the control group
      and isoimmune group were artificially inseminated following the 6th and 7th
      immunization with untreated sperm or sperm pretreated with antisperm IgG or Fab
      in quadruplicates and allowed to complete a pregnancy. Three fertility trials
      were performed to investigate the therapeutic efficacy of Fab-coated sperm to
      restore fertility in isoimmune does. In the 3 fertility trials, none of the
      isoimmune does inseminated with untreated sperm had a successful pregnancy. By
      contrast, in 3 cases, rabbit sperm pretreated with antisperm Fab were able to
      fertilize in vivo with successful pregnancy in a control and isoimmune doe
      resulting in normal offspring. These results demonstrate that in vitro treatment
      of sperm with antisperm Fab fragments had a protective effect from isoimmune
      attack in vivo. The successful use of Fab fragments for reversal of antisperm
      antibody-mediated infertility observed in the isoimmune rabbit model offers the
      prospect of a new means of restoring fertility in some isoimmune women.

PMID- 8564384
TI  - In vitro and in vivo comparative studies on chelation of aluminum by some
      polyaminocarboxylic acids.
AB  - Since desferrioxamine exhibits toxic effects, the possible use of several other
      therapeutic agents in acute aluminum intoxication has been investigated in this
      study. The potential for the chelation of aluminum (Al) by different compounds
      has been first determined using two in vitro techniques. The formation of stable
      complexes with Al in an aqueous solution has been evaluated by using pulse
      polarography. This technique allows the influence of temperature and of calcium
      (Ca) to be studied for each compound. Certain compounds (HEDTA, DTPA) showed
      extensive chelation in the presence of Ca2+ at a temperature of 37 +/- 1 degree
      C. An ultrafiltration technique combined with Al determination by atomic emission
      spectroscopy (A.E.S.) has allowed the ability of different substances to complex
      Al that was previously bound to serum proteins, to be estimated. The kinetics of
      chelation and the minimum efficient concentration have been determined for all of
      the products studied. The real efficacies of the compounds were studied by in
      vivo investigations to compare the effectiveness of the best chelating agents
      (DFO, HEDTA and EDTA) on the distribution and excretion of Al, after repeated
      i.p. administration to rats. HEDTA shows a chelation potential as widely active
      as the DFO potential.

PMID- 8564385
TI  - Suppressive effect of clenbuterol on citric acid-induced cough reflex in guinea
      pigs.
AB  - We previously demonstrated that clenbuterol suppressed bronchial
      hyperresponsiveness in acute bronchitic models. However the effect of clenbuterol
      on the cough reflex, the main symptom of acute bronchitis, is not clear. The
      present study was thus undertaken to investigate the influence of clenbuterol on
      the cough reflex. Oral administration of clenbuterol (3 and 10 micrograms/kg) to
      guinea pigs markedly inhibited the increase in the respiratory resistance in
      response to 5-HT in a dose-dependent manner. At doses of 10 micrograms/kg and
      above, clenbuterol significantly inhibited the cough reflex induced by citric
      acid in guinea pigs. These doses are comparable with those causing broncho
      dilation as described above, suggesting that the suppressive effect of
      clenbuterol on the cough reflex in guinea pigs may result from mainly its broncho
      dilative action via stimulation of beta-2 adrenoceptors in airway smooth muscles
      however, other mechanisms cannot be ruled out. These results indicate that this
      agent may be useful for treatment of cough, the main symptom of acute bronchitis.

PMID- 8564386
TI  - Protective effects of doxycycline in mesenteric ischemia and reperfusion.
AB  - In rats splanchnic artery occlusion (SAO) of the celiac and superior mesenteric
      arteries for 1 hr., followed by a period of reperfusion initiates a severe form
      of circulatory shock, which typically leads to death within 2 hrs, characterized
      by multiorgan failure in which neutrophils play a central role. Doxycycline (Dc)
      pretreatment (10mg/kg; 2 hrs. prior to occlusion) significantly increased the
      survival time and leukocytes retention in circulation and decreased the
      hemoglobin levels in the contents of the small intestine. Dc did not influence
      serum alanine aminotransferase or amylase levels (marker enzymes for liver and
      pancreas damages respectively) at the time of death. Creatinine phosphate kinase,
      a marker of cardiotoxicity, was significantly increased in serum from Dc-treated
      rats. We conclude that pretreatment with Dc has a protective effect in the SAO
      rat model and this protection cannot be ascribed directly to a specific sparing
      influence on the liver, pancreas, or heart.

PMID- 8564387
TI  - A sensitive enzyme immunoassay for cyclosporin A using antibodies generated
      against a novel hapten.
AB  - A simple and sensitive enzyme immunoassay for cyclosporin A has been developed.
      Cyclosporin A (CsA) antibodies were generated in rabbits using a novel hapten
      (CsA-C6) derived from ozonolysis of a double bond at residue 1 followed by
      reaction with 6-amino hexanoic acid. The antibodies generated from CsA-C6
      recognized the spacer arm between the hapten and the carrier protein. A
      heterologous bridge strategy for haptenenzyme conjugate was used to improve the
      sensitivity. A hemisuccinyl ester of cyclosporin A alcohol (CsA-C4) was
      synthesized, conjugated to horseradish peroxidase and used as the enzyme labeled
      hapten. A high sensitivity enzyme immunoassay for CsA was developed. The
      concentration that gave 50% inhibition of binding was 1 ng/ml (8.3 x 10(-10)M) of
      CsA. The specificity of the antibodies was examined against various metabolites.
      Metabolites with structural modifications at distal residues 4, 8 and 9 showed
      the least crossreactivity, whereas metabolites derived from residue 1 exhibited
      full crossreaction as expected.

PMID- 8564388
TI  - Macrophage enhancement of galactosamine hepatotoxicity using a rat hepatocyte
      culture system.
AB  - Prior administration of endotoxin to rats is known to aggravate the
      hepatotoxicity of galactosamine. It has been proposed that this exacerbation
      occurs as a result of the release of cytokines and other humoral factors by
      resident macrophages (Kupffer cells). In order to study this phenomenon we have
      utilized a co-culture system consisting of rat activated peritoneal macrophages
      and rat hepatocytes. Peritoneal macrophages were isolated and cultured; LPS was
      added as a macrophage activator 16 hours later. Rat hepatocytes were isolated and
      plated in Transwell COL inserts, which were placed in wells with and without
      activated macrophages. Cytotoxicity was determined 24 hours later by measuring
      lactate dehydrogenase (LDH) leakage into the culture medium. In the presence of
      activated macrophages an approximate 3-fold increase in galactosamine-induced
      hepatocyte toxicity was observed, as compared to the toxicity in hepatocytes
      cultured alone. Using this co-culture system, we examined the role of leukotriene
      D4 (LTD4) and nitric oxide (NO) as mediators of this enhancement. Addition of
      either LTD4 or NO to hepatocytes cultured alone did not exacerbate galactosamine
      toxicity. Furthermore, addition of the LTD4 receptor antagonist SK & F 104353 (50
      microM) or the NO synthase inhibitor N-monomethyl-L-arginine (1.0 mM) to
      macrophage/hepatocyte co-cultures did not attenuate the enhanced galactosamine
      hepatocyte toxicity in the co-cultures. Collectively, these data indicate that
      this co-culture system will be useful in examining the mechanism of macrophage
      enhancement of chemical-induced hepatoxicity and, further, suggest that LTD4 and
      NO may not be involved in the exacerbation of galactosamine toxicity to
      hepatocyte cultures.

PMID- 8564389
TI  - Ionophoretic properties of the non-sulfonylurea hypoglycemic agents A-4166 and
      KAD-1229.
AB  - The non-sulphonylurea hypoglycaemic agents A-4166 and KAD-1229 were both found to
      cause 45Ca or 22Na translocation from an aqueous medium into an organic
      immiscible phase. This ionophoretic effect was more marked with A-4166 than KAD
      1229, in mirror image of their insulinotropic potency. Such a dissociated
      behaviour argues against the view that the ionophoretic properties of these
      agents represent a major determinant of their insulinotropic action.

PMID- 8564390
TI  - Transport and metabolism of glutathione isopropyl ester in cerebrospinal fluid.
AB  - The transport of glutathione (GSH) or glutathione isopropyl ester (GSH isopropyl
      ester) to the cerebrospinal fluid (CSF) in rats was estimated by levels of GSH or
      GSH isopropyl ester and their metabolites in CSF 30 min after the intravenous
      administration of GSH or GSH isopropyl ester (300 mg/kg). Although the CSF uptake
      of GSH isopropyl ester was almost equal to that of GSH as evidenced by about a
      two-fold increase in the amount of non-protein sulfhydryl groups in CSF, the sum
      of GSH isopropyl ester and GSH concentrations in the CSF after GSH isopropyl
      ester treatment was increased by 32% compared with saline-treated controls. On
      the other hand, treatment with GSH had no significant increase in GSH levels in
      CSF but increased its metabolite levels, such as cysteinyl-glycine and cysteine.
      GSH isopropyl ester was less metabolized than GSH. GSH isopropyl ester had low
      affinity to purified gamma-glutamyl transpeptidase, a key enzyme for metabolism
      of GSH in the choroid plexus, supporting the finding that GSH isopropyl ester is
      more stable than GSH in CSF. These results are compatible with our previous
      report (Yamamoto et al. (1993) showing that the protective action of GSH
      isopropyl ester against cerebral ischemia was greater than that of GSH in rats.
      GSH isopropyl ester may be a useful agent which protects the brain from the
      damage associated with oxygen-related toxicities by increasing GSH levels in the
      CSF.

PMID- 8564391
TI  - Isolation and electrophoretic analysis of human serum proteoglycans and their
      reaction with nickel in vitro.
AB  - Human serum proteoglycans were isolated from random serum samples from healthy
      blood donors by cetylpyridinium chloride precipitation technique. Their
      concentration (14 +/- 6 mg/l +/- S.D.) corresponded to that of other mammals.
      Electrophoretic separation on polyacrylamide gel with a subsequent staining for
      glycans revealed four major bands from 175 to 80 kDa. Incubation in vitro with
      0.1, 0.2 or 0.5 mM NiCl2 for 1 h caused a loss of glycan chains according to the
      nickel concentration. In the electrophoretic analysis, all proteoglycan bands
      diminished due to the incubation with the nickel salt. It seems that this
      approach could be used as a model for effects of chemicals on the proteoglycan
      metabolism.

PMID- 8564392
TI  - The effects of contextual cues on making occupational and gender categorizations.
AB  - We report one study investigating how persons are categorized when the targets
      are presented with contextual cues. Using photos of either persons in
      occupational clothing and in occupational contexts or photos of college students
      and without distracting stimuli, the response times to verify various group
      memberships were tested, with the underlying interest of determining how persons
      are perceived when the persons are clearly members of multiple categories.
      Consistent with past research, when using rather simplistic photos, women were
      categorized as women faster than men were categorized as men. With occupational
      photos, however, women were not categorized as women faster than men were as men,
      nor were men categorized by occupation faster than were women, contrary to
      predictions derived from the 'white male default' (Zarate & Smith, 1990). Rather,
      for female stereotypic occupations, female targets were classified by occupation
      faster than were male stereotypic occupations, male targets were classified by
      occupation faster than were female targets. Across all comparisons, subjects
      categorized same-sex targets faster than other sex targets. Results are discussed
      for their implications for various person perception models.

PMID- 8564393
TI  - Power, gender stereotypes and perceptions of heterosexual couples.
AB  - This paper examines the relation between power attributed to members of
      heterosexual couples and the perception of their personalities in terms of gender
      stereotyped traits. Three-hundred and fifty adults, native French subjects (women
      and men) participated in the study. They attributed daily family tasks and
      decisions to the target persons; then, they described them on the Bem Sex-Role
      Inventory. The results indicated strong correlations between observers'
      representations of power distribution in the couple and the gender related
      personality descriptions of the couple. The attribution of 'instrumental' traits
      increased (and 'expressive' traits decreased) according to the degree of power
      assigned to the target person of either sex. On the 'instrumentality' dimension,
      accentuation of perceptions of people in gender role inconsistent positions was
      also observed. The simultaneous influences of general gender stereotypes and
      specific relations between the gender roles in dyads on the perception of
      individuals are discussed. It is proposed that social relations of dominance
      provide a model for the construction of gender stereotypes and their contextual
      applications.

PMID- 8564394
TI  - Change in stereotypic perceptions of familiar and unfamiliar groups: the
      pervasiveness of the subtyping model.
AB  - The present study examined change in stereotypic perceptions of occupational
      groups, using a 2 (pattern of presented stereotype inconsistent information:
      concentrated in a few members vs. dispersed across all members) X 2 (perceived
      group variability: homogeneous vs. heterogeneous) X 2 (familiarity with the
      group: familiar vs. unfamiliar) design, following the procedure used by Hewstone,
      Johnston & Aird (1992). There was no support for the 'conversion' model.
      Stereotype change was generally greater in dispersed than in concentrated
      conditions, while subtyping was stronger in concentrated than in dispersed
      conditions. There was limited evidence that familiarity might moderate the
      effects of pattern of disconfirming instances. Results were interpreted in terms
      of a prototype version of the subtyping model.

PMID- 8564395
TI  - Conjugation of doxorubicin to monoclonal anti-carcinoembryonic antigen antibody
      via novel thiol-directed cross-linking reagents.
AB  - In order to improve the available methods to produce an immunoconjugate the use
      of longer heterobifunctional cross-linking reagents were investigated. Two new
      maleimidobenzoyl spacers have been synthesized in a one step process from 4
      maleimidobenzoic acid. The new heterobifunctional cross-linking reagents were
      fully characterized by their IR, 1H NMR, 13C NMR and mass spectra. These spacers
      are selectively attached to NH2-3' of the daunosamine moiety of doxorubicin. The
      spacer-doxorubicin derivatives were also characterized by 1H NMR spectrometry
      before coupling to thiol groups of thiolated anti-carcinoembryonic antigen (CEA)
      monoclonal antibody (11-285-14). These conjugates contain 1.51-3.44 molecules of
      drug for each molecule of monoclonal antibody (MAb).

PMID- 8564396
TI  - Novel doxorubicin-monoclonal anti-carcinoembryonic antigen antibody
      immunoconjugate activity in vitro.
AB  - Doxorubicin was modified with five different heterobifunctional reagents to
      produce drug analogs containing 3'-N-amide or C-13 hydrazone linkage with
      maleimide. Synthesis and characterization of two new reagents, 4
      maleimidobenzohydrazide trifluoroacetate salt (13) and N-(4-maleimidobenzoyl)-6
      aminocaprohydrazide trifluoroacetate salt (14) are described here. All Dox
      maleimido derivatives were conjugated to thiolated anti-carcinoembryonic antigen
      monoclonal antibody, 11-285-14, via a Michael addition reaction. Antibody
      directed cytotoxicity was demonstrated with the MTT assay using combinations of
      antigen-positive and antigen-negative cell lines. The immunoconjugates prepared
      from Dox 3'-N-amide analogs are not active in vitro, however, Dox(hydrazone
      linked) immunoconjugates are selectively toxic to the CEA positive cell line.

PMID- 8564397
TI  - Identification of an aldose reductase inhibitor site by affinity labeling.
AB  - Animal studies indicate that aldose reductase inhibitors represent a
      pharmacological method for inhibiting the onset of diabetic complications that is
      independent of blood sugar control. This has spurred the development of aldose
      reductase inhibitors (ARIs). To facilitate the rational development of more
      potent and direct ARIs, more specific knowledge of the structural and
      pharmacophoric requirements of the site at which ARIs interact are required. Co
      crystallization of human placental aldose reductase with the inhibitor
      zopolrestat has been reported to result in a complex where the inhibitor is
      almost completely sequestered in the hydrophobic pocket which forms the substrate
      site. Zopolrestat's observed location, which makes the active site pocket
      inaccessible to solvent or further productive binding of substrate, is not
      supported by published inhibitor structure-activity relationships (SAR) studies
      or kinetic results which indicate that aldose reductase inhibitors such as
      zopolrestat are either non-competitive or uncompetitive inhibitors. Using a 5
      iodoacetamido analog of alrestatin as an affinity labeled aldose reductase
      inhibitor, an inhibitor binding site on aldose reductase has been located. This
      inhibitor binding site contains a number of pharmacophoric elements previously
      proposed for the inhibitor site. Its location and composition is consistent with
      reported kinetic data, SAR observations, stereochemical requirements, and quantum
      chemical calculations.

PMID- 8564398
TI  - Automated solid phase synthesis of cyclic oligonucleotides: a further
      improvement.

PMID- 8564400
TI  - Anti-AIDS agents--XIX. Neotripterifordin, a novel anti-HIV principle from
      Tripterygium wilfordii: isolation and structural elucidation.
AB  - A new kaurane type diterpene lactone, neotripterifordin (1), has been isolated
      from the roots of Tripterygium wilfordii. The structure of 1 was elucidated by
      spectroscopic methods, which included the concerted application of a number of 2
      D NMR techniques including 1H-1H COSY, phase-sensitive NOESY, HETCOR, and long
      range HETCOR. Compound 1 showed potent anti-HIV replication activity in H9
      lymphocyte cells with an EC50 of 25 nM and TI of 125.

PMID- 8564399
TI  - Comparative molecular field analysis of selective A3 adenosine receptor agonists.
AB  - A series of 48 N6-benzyladenosine 5'-uronamide derivatives has been described
      recently as moderately selective A3 adenosine receptor agonists of nanomolar
      potency (Gallo-Rodriguez, C. et al. J. Med. Chem. 1994, 37, 636). Quantitative
      structure activity relationships in this series, including some novel
      derivatives, have been investigated using a Comparative Molecular Field Analysis
      (CoMFA), with emphasis on the N6-substituent. The resulting three dimensional
      pharmacophore model defines the steric and electronic factors which modulate in
      vitro affinities in binding to rat brain A3 adenosine receptors. The model
      indicates a positive correlation of affinity with the steric characteristics of
      the compounds (major factor), particularly toward the 3-position of the benzyl
      ring of N6-benzyl NECA, and a weak correlation with the electrostatic effects of
      the N6-substituent. A comparison of active and inactive compounds using volume
      maps showed that bulk at the 3-position of the benzyl ring of the molecule is
      conducive to high affinity at A3 receptors, while steric bulk at other positions
      of the benzyl ring leads to poor binding. t-Boc-amino acid conjugates of a 3
      aminobenzyl derivative were synthesized to probe the steric and hydrophobic
      limitations at that position. We have discovered a subregion of the N6-benzyl
      binding pocket occupied by a 3-(L-prolylamino) group that is sterically
      disallowed at A3 receptors and allowed in A1 and A2a receptors. 6-N
      Phenylhydrazino and 6-O-phenylhydroxylamino derivatives, incorporating major
      changes in electrostatic character of the ligand proximal to the purine, were
      predicted by the CoMFA model to have high A3 affinity. Such analogs were
      synthesized and found to be well tolerated at the A3 receptor binding site.

PMID- 8564401
TI  - Cloning and overexpression of rhamnose isomerase and fucose isomerase.
AB  - Rhamnose isomerase and fucose isomerase were overexpressed in E. coli, purified
      and characterized. The rhamnose isomerase gene was ligated to the restriction
      sites of PstI and Hind III of vector pTrcHis and the fucose isomerase gene was
      ligated to the EcoRI and PstI sites of vector pKK223-3 for overexpression of the
      enzymes in E. coli XL1-Blue MRF. Approximately 16,500 U of active fucose
      isomerase and 2400 of rhamnose isomerase can be obtained per liter of culture
      from these expression systems.

PMID- 8564402
TI  - Fluorescent and biotinylated analogues of docetaxel: synthesis and biological
      evaluation.
AB  - Six novel docetaxel analogues that possess a N-(7-nitrobenz-2-oxa-1,3-diazo-4
      yl)amido-6-caproyl chain in position 7 or 3' (11 and 16a), a N-(7-nitrobenz-2-oxa
      1,3-diazo-4-yl)amido-3-propanoyl group at 3' (16b) and a 5'-biotinyl amido-6
      caproyl chain in position 7, 10 or 3', respectively, have been synthesized. These
      compounds exhibit activity against microtubule disassembly similar to that of
      docetaxel but show discrepant activities on living cells. Although addition of
      microtubules to 11, 16a and b enhance their fluorescence, no shift of the
      emission maxima was observed. The fluorescent docetaxel derivatives show a
      specific labeling of microtubules in living cells, demonstrating that the
      microtubule cytoskeleton constitutes their main subcellular localization.

PMID- 8564403
TI  - Synthesis of [Phe(4F)3]thymopoietin II and examination of its immunological
      effect on the impaired blastogenic response of T-lymphocytes of uremic patients.
AB  - [Phe(4F)3]thymopoietin II was synthesized using a conventional solution method.
      The deprotection of the protected [Phe(4F)3]thymopoetin II was achieved by
      treatment with 1 M trifluoromethanesulfonic acid:thioanisole (molar ratio 1:1) in
      trifluoroacetic acid in the presence of dimethylselenide and m-cresol. The
      synthetic f1p4(4F)3]thymopoietin II and thymopoietin II were tested for effect on
      impaired T-lymphocyte transformation by phytohemagglutinin in uremic patients
      suffering from recurrent infectious diseases. The restoring activity on the
      impaired phytohemagglutinin stimulation of T-lymphocytes was obtained after
      incubation of peripheral lymphocytes isolated from uremic patients with the
      synthetic [Phe(4F)3]thymopoietin II. This peptide exhibited far stronger
      restoring effect than that of our synthetic thymopoietin II.

PMID- 8564404
TI  - Synthesis and antiviral effects of 2-heteroaryl substituted adenosine and 8
      heteroaryl substituted guanosine derivatives.
AB  - 2-(2"- and 3"-Thienyl)adenosine and the corresponding furyl derivatives were
      prepared though Pd(0)-catalyzed coupling of 2',3',5'-tri-O-(t-butyldimethylsilyl)
      2-iodoadenosine with the appropriate tributyltin derivatives followed by
      deprotection. Preparation of the 8-(2"- and 3"-thienyl)guanosines and 8-(2"- and
      3"-furyl)guanosines followed a similar route. Antiviral properties of these
      compounds and the related 2,6-diaminopurine ribofuranosides were of no
      pharmacological interest.

PMID- 8564405
TI  - Aromatic hydroxylation by Fenton reagents (reactive intermediate
      [Lx+FeIIOOH(BH+)], not free hydroxyl radical (HO.)).
AB  - Several iron complexes [FeII(bpy)2(2+), FeII(OPPh3)4(2+), and FeII(PA)2] in
      combination with hydrogen peroxide (HOOH) catalytically hydroxylate aromatic
      substrates (ArH). The base-induced nucleophilic addition of HOOH to the
      electrophilic iron center yields the reactive intermediate of Fenton reagents
      [FeIILx2+ + HOOH<-->Lx+FeIIOOH(BH+)(1)]. The latter includes a 'stabilized'
      hydroxyl radical that is able to replace an aromatic hydrogen (H) with a hydroxyl
      group (HO) via an initial addition reaction. With PhCH3 and PhCH2CH3 as
      substrates free HO. (from the radiolysis of H2O) reacts via aryl addition (97 and
      85%, respectively) to give Ar-Ar as the predominant product, whereas 1 favors H
      atom abstraction from the alkyl group (50 and 80%, respectively) and the only
      detectable products from aryl addition are the respective substituted phenols
      (o:p-ArOH). Other substituted benzenes (PhX) undergo addition by free HO at the
      ortho and para aryl carbons (o:p ratio, 2), followed by dimerization and
      elimination of two H2O molecules to yield substituted biphenyls. In contrast, 1
      reacts with PhX to yield substituted phenol (ArOH; o:p ratio, 0.5-1.1). With
      phenol (PhOH) as the substrate, reaction with 1 yields mainly catechol (o
      Ar(OH)2; o:p ratio, 20). In a solvent matrix of MeCN:H2O (3:1 mol:mol ratio) the
      reaction efficiencies with FeII(bpy)2(2+) and FeII(OPPh3)4(2+) for the
      hydroxylation of benzene to phenol are 36 and 42%, respectively (product per
      HOOH).

PMID- 8564406
TI  - Description of hydrophobicity parameters of a mixed set from their three
      dimensional structures.
AB  - The logarithm of capacity factors (log k') previously measured from the reversed
      phase high-performance liquid chromatography (RP-HPLC) and the octanol-water
      partition coefficients (log P) of a mixed set of substituted benzene, furan,
      benzofuran, pyrrole, 1-Me-pyrrole, indole, and N-methyl indole derivatives are
      correlated with the descriptors obtained from their three-dimensional structures
      using the comparative molecular field analysis (CoMFA) approach. The results
      provide an example where log k' and log P values are calculated directly from the
      three-dimensional structures for a mixed set of compounds.

PMID- 8564407
TI  - New phospholipase A2 inhibitor: synthesis and inhibition mechanism of
      oxazolidinone phospholipid analog.
AB  - (R)-3-Dodecanoyl-4-phosphatidylcholino-hydroxymethyl-2-oxazolidino ne (7), which
      is a new glycerophospholipid analog, was synthesized starting from (S)-glycidol
      through a 4-alkylsilyoxymethyl derivative and N-acyl-4-hydroxymethyl derivative.
      The cyclic amide analog 7 showed strong inhibitory activity toward both Group I
      and II PLA25, but the inhibitory potency of 7 was slightly weaker than that of
      the linear amide analog (R)-1, which had been developed by de Haas et al.
      (Biochem. Biophys. Acta 1990, 1043, 67). The interactions of 7 with human
      secretory PLA2 was investigated by computer modeling in comparison with those of
      the linear amide analog 1. The results of the computer modeling were very
      compatible with those of the inhibitory activities toward PLA2S, and the both
      results showed that the binding mode of the oxazolidinone analog 7 was very
      similar to that of the genuine substrate and was different from that of the
      linear amide analog 1.

PMID- 8564408
TI  - Amino hydroxamic acids as potent inhibitors of leukotriene A4 hydrolase.
AB  - Leukotriene A4 hydrolase is a zinc-containing enzyme which catalyzes the
      hydrolysis of LTA4 to LTB4, a proinflammatory mediator. The enzyme also exhibits
      an aminopeptidase activity. Due to its biological importance, it is of
      considerable interest to develop selective inhibitors of this enzyme. The design
      and synthesis of a number of potent beta-amino hydroxylamine and amino hydroxamic
      acid inhibitors are described here. It was found that having a free amine was
      essential for high activity. Hydroxylamines were found to be about an order of
      magnitude less potent than their analogous hydroxamic acids. Our investigation of
      amino hydroxamic acids as inhibitors of leukotriene A4 hydrolase has led to the
      development of hydroxamates 16 and 17, which are among the most potent inhibitors
      found to date. These, compounds were found to be competitive inhibitors with Ki
      values of 1.6 nM and 3.4 nM respectively, against the peptidase activity.
      Inhibitor 16 has an IC50 value of < or = 0.15 microM against the epoxide
      hydrolase activity and is also potent against the production of LTB4 by isolated
      polymorphonuclear leukocytes (PMNL) activated with ionophore A23187 (IC50
      approximately 0.3 microM).

PMID- 8564409
TI  - Cycloaddition and related reactions of cephalosporin antibiotics.

PMID- 8564410
TI  - Syntheses, activity and modeling studies of 3- and 4-(sulfo- and
      sulfonamidoalkyl)pyridine and piperidine-2-carboxylic acid derivatives as analogs
      of NMDA receptor antagonists.
AB  - A series of 3- and 4-(sulfo- and sulfonamidoalkyl)pyridine and piperidine-2
      carboxylic acid derivatives as analogs of NMDA receptor antagonists was prepared.
      Affinity for the NMDA receptor was determined by binding assays using the
      specific radioligand [3H] (2SR,4RS)-4-(phosphonomethyl)piperidine-2-carboxylic
      acid (CGS-19755). The 3-alkylsulfonyl moiety was introduced by selective
      reduction of a carboxylic acid function followed by bromination, substitution by
      Na2SO3 and catalytic reduction. For the 4-alkylsulfonic derivatives the crucial
      step was the introduction of the 2-cyano function and its further conversion to 2
      carboxylic acid. The most potent compound of the series was the pyridine (11a) [4
      (sulfomethyl)pyridine-2-carboxylic acid] with a modest IC50 of 40 microM. A
      molecular modeling study has been undertaken to understand the pharmacological
      results. In a first step, a comparative modeling study of the active pyridine and
      the poorly active piperidine sulfonic acid derivatives 11a and 10a [4
      (sulfomethyl)piperidine-2-carboxylic acid] and of the phosphonic homologues was
      performed. We propose that the binding geometry of the sulfonic moiety within the
      NMDA receptor is different from that of the phosphonic containing antagonists. In
      order to test this assumption, we have made, in a second step, a complete
      conformational analysis of the sulfonic acid derivatives, as well as some analogs
      taken from the literature, either active or inactive as NMDA antagonists. A
      preferred conformation of the sulfonic acids is proposed.

PMID- 8564411
TI  - Synthesis and evaluation of pyrazolignans. A new class of cytotoxic agents.
AB  - A series of fused pyrazole derivatives of cyclolignans have been prepared through
      simple chemical routes and evaluated for their cytotoxic activities in culture
      cells of P-388 murine leukemia, A-549 lung carcinoma and HT-29 colon carcinoma.
      Despite the lack of the lactone moiety in their structures, they show IC50 values
      at microM levels.

PMID- 8564412
TI  - The polypeptide 3(10)-helix as a template for molecular recognition studies.
      Structural characterization of a side-chain functionalized octapeptide.
AB  - A N alpha-blocked, Aib-rich octapeptide methylamide containing two N omega
      benzoylated L-Lys residues at positions 3 and 6 was synthesized by solution
      methods and fully characterized. A solution and crystal-state conformational
      analysis, performed by using FT-IR, 1H NMR, CD, and X-ray diffraction techniques,
      showed that the peptide is folded into a regular, right-handed 3(10)-helix
      stabilized by seven consecutive N-H...O=C intramolecular H-bonds of the beta-turn
      III type. The two benzamidobutyl L-Lys side chains, located on the same side of
      the helix after one complete turn, generate a cleft the minimal width of which
      was found to be 3.47 A.

PMID- 8564413
TI  - Stereoselective synthesis, chemistry and antiviral evaluation of 1-(2,3-dideoxy-3
      C-hydroxymethyl-beta-D-threo-pentofuranosyl)thymine derivatives.
AB  - A series of novel 3'-C-branched 2',3'-dideoxynucleosides have been synthesized
      and evaluated as anti-HIV agents. Hydroboration of 2',3'-dideoxy-3'-C-methylene
      nucleoside proceeded regio- and stereoselectively to give 1-(2,3-dideoxy-3-C
      hydroxy methyl-5-O-trityl-beta-D-threo-pentofuranosyl)thymine (5) after
      oxidation. 3'-C-Chloromethyl and 3'-C-iodomethyl 5'-O-protected 2',3'
      dideoxynucleosides 9 and 12 were obtained from 5 by reaction with carbon
      tetrachloride/triphenylphosphine and methyltriphenoxyphosphonium iodide,
      respectively. Arbuzov reaction of 12 with triethyl phosphite afforded 3'-C
      (diethyl-phosphono)methyl 5'-O-protected 2',3'-dideoxynucleoside 14. Compounds 5,
      9, 12 and 14 were detritylated to give 1-(3-C-chloromethyl-2,3-dideoxy-beta-D
      threo-pentofuranosyl)thymine (10), 1-(2,3-dideoxy-3-C-hydroxymethyl-beta-D-threo
      pentofuranosyl)-thymine (11), 1-(2,3-dideoxy-3-C-iodomethyl-beta-D-threo
      pentofuranosyl)thymine (13) and 1-(2,3-dideoxy-3-C-(O,O'-diethylphosphono)methyl
      beta-D-threo- pentofuranosyl)thymine (15), respectively. These nucleoside
      analogues were evaluated for antiviral activity against human immunodeficiency
      virus type 1 (HIV-1) and herpes simplex virus type 1 (HSV-1) in vitro. Compound 5
      demonstrated selective antiviral activity against HIV-1 but not HSV-1.

PMID- 8564414
TI  - Amides of piperidine, morpholine and piperazine substituted 1-phenylethylamines:
      inhibitors of acylCoA:cholesterol acyltransferase (ACAT) activity in vitro and in
      vivo.
AB  - Amides of some substituted 1,2-diarylethylamines have been shown to exhibit
      potent acylCoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) inhibitory
      activity in vitro in microsomal ACAT assays but show poor in vivo activity in a
      cholesterol-fed hamster model. In an effort to design ACAT inhibitors that are
      potent in both our in vitro and in vivo assays a series of amides of piperidine,
      morpholine and piperazine substituted 1-phenylethylamines were synthesized.
      Compounds of this series were found to be very potent inhibitors of ACAT in a
      microsomal ACAT assay and also exhibited potent activity in a cholesterol-fed
      hamster model.

PMID- 8564415
TI  - Chemical synthesis of allysine ethylene acetal and conversion in situ into 1
      piperideine-6-carboxylic acid: key intermediate of the alpha-aminoadipic acid for
      beta-lactam antibiotics biosynthesis.

PMID- 8564416
TI  - Antitumor and antimicrobial activities of Fe(II)/Fe(III) complexes derived from
      some heterocyclic compounds.
AB  - The antitumor activities of some Fe(II)/Fe(III) complexes containing 1,3-diacetyl
      2H-benzimidazole-2-thione along with a few derivatives of 1,2,4-triazol, 1,3,4
      oxadiazole and 1,3,4-thiadiazole as co-ligands have been investigated.
      Antibacterial and antifungal activities of disulfido-/dichloro-bridged dinuclear
      Fe(III)/Fe(II) complexes containing similar heterocycles as terminal ligands have
      also been investigated.

PMID- 8564417
TI  - Effects of chirality and substituents at carbon 3 in dihydroxyacetone-phosphate
      analogues on their binding to rabbit muscle aldolase.
AB  - A series of dihydroxyacetone-phosphate (DHAP) analogues has been synthesized,
      differing in their stereochemistry and functionality at C-3. The kinetic effects
      of these compounds on the enzyme aldolase (EC 4.1.2.13) have been studied and
      differing modes of action observed. Competitive and time dependent reversible
      inhibition have been shown to take place both with and without borohydride
      detected formation of an immonium ion.

PMID- 8564418
TI  - Synthesis, antioxidant properties, biological activity and molecular modelling of
      a series of chalcogen analogues of the 5-lipoxygenase inhibitor DuP 654.
AB  - 2-Phenylsulfenyl- (1b), 2-phenylselenenyl- (1c) and 2-phenyltellurenyl-1-naphthol
      (1d) were prepared and their antioxidative properties evaluated in comparison
      with 2-benzyl-1-naphthol (1a; DuP 654). 2-Phenyltellurenyl-1-naphthol had a
      significantly lower (1.00 V versus SCE) oxidation potential than the other three
      compounds (1.24, 1.27 and 1.25 V, respectively, versus SCE for compounds 1a, 1b
      and 1c) as determined by cyclic voltammetry. In contrast to the other materials,
      compound 1d was able to catalyze the reduction of hydrogen peroxide in the
      presence of thiols as stoichiometric reducing agents. The organotellurium
      compound was also the most efficient inhibitor of azo-initiated peroxidation of
      linoleic acid in a two-phase model system. Ab initio geometry optimization at the
      3-21G(*) level revealed infinitesimal changes in the molecular conformations of
      the carbon, sulfur, selenium and tellurium analogues. As judged by their ability
      to inhibit stimulated LTB4 biosynthesis in human neutrophils, compounds 1a-1d all
      turned out to be highly potent 5-lipoxygenase inhibitors with IC50-values ranging
      from 0.40 microM for 2-benzyl-1-naphthol (1a) to 0.063 microM for 2
      phenyltellurenyl-1-naphthol (1d).

PMID- 8564419
TI  - Structure-activity studies of phosphorylated peptide inhibitors of the
      association of phosphatidylinositol 3-kinase with PDGF-beta receptor.
AB  - Phosphorylated pentapeptides derived from Tyr751 of the PDGF-beta receptor
      (pTyr751-Val-Pro-Met-Leu, pTyr = phosphotyrosine) were prepared to examine their
      ability to inhibit the association of the C-terminal SH2 domain of the p85
      subunit of phosphatidylinositol 3-kinase (PI 3-kinase) with the PDGF-beta
      receptor. Peptidic analogs were prepared to examine the importance of the amine
      and carboxy terminus and specific amino acids via alanine/D-amino acid scans and
      site specific modifications. Several of these peptides had submicromolar
      activity. In particular, it was shown that neutralization of the amine and
      carboxy terminus led to analogs with enhanced activity. In addition, it was
      determined that only minimal modifications were allowed for pTyr and Met, while
      the other positions were quite tolerant of modification.

PMID- 8564420
TI  - Solution structure of endothelin B receptor selective antagonist RES-701-1
      determined by 1H NMR spectroscopy.
AB  - The three-dimensional structure of the endothelin B receptor (ETB) selective
      antagonist RES-701-1 has been determined by 1H NMR in deuterated dimethyl
      sulphoxide. RES-701-1 consists of 16 amino acid residues with a novel internal
      linkage between the beta-carboxyl group of Asp9 and the alpha-amino group of
      Gly1. The structural calculations were carried out with the combined use of
      distance geometry and simulated annealing. The result indicates that RES-701-1
      adopts an extraordinary folding; the 'tail' (Trp10-Trp16) passes through the
      'ring' region (Gly1-Asp9). Several critical NOEs directly support this
      extraordinary folding. The folding of RES-701-1 turned out to be the same as that
      Frechet et al. calculated for RP 71955 which possesses the same internal linkage
      as RES-701-1. The obtained structure suggested that the region consisting of
      Thr6, Ala7, Tyr14 and Tyr15 and/or, the region consisting of Asn2, Tyr14 and
      Tyr15 are involved in a binding with ETB.

PMID- 8564421
TI  - Synthesis of key analogs of bleomycin A2 that permit a systematic evaluation of
      the linker region: identification of an exceptionally prominent role for the L
      threonine substituent.
AB  - The synthesis of a full series of analogs 2b-k of deglycobleomycin A2 (2a)
      containing systematic variations in the linker domain of bleomycin A2 (1) is
      described. The agents 2b-k, which are not accessible through structural
      modification of 1 or 2a, constitute key substructure analogs incorporating deep
      seated structural modifications in the linker domain capable of delineating the
      contribution of the individual backbone substituents to the DNA cleavage
      efficiency, characteristic DNA cleavage selectivity, and double strand to single
      strand DNA cleavage ratio. The comparative examination of the DNA cleavage
      properties of the Fe(II) and Fe(III) complexes of 2a-k upon activation by O2
      thiol or H2O2, respectively, revealed several characteristic features and trends.
      First, none of the substituents affect the characteristic 5'-GC, 5'-GT > 5'-GA
      DNA cleavage selectivity of bleomycin A2. In contrast, an exceptionally prominent
      role for the L-threonine substituent and an important role for the C4-methyl
      substituent of the (2S,3S,4R)-4-amino-3-hydroxy-2-methylpentanoic acid subunit
      were observed on the DNA cleavage efficiency of the agents. Similarly, the L
      threonine substituent was found to substantially increase the ratio of double
      strand to single strand DNA cleavage events (2-3 times). In a w794 DNA cleavage
      assay, shortening the linker region by two carbons resulted in an exceptionally
      large reduction in DNA cleavage efficiency (125 times) and provided an agent that
      was only 1.3 times more effective than Fe(III) indicating that this deep-seated
      modification essentially destroys the DNA cleavage capabilities of the agent. The
      L-threonine substituent contributes in an exceptional manner, and its removal
      resulted in a 25 times reduction in DNA cleavage efficiency. A substantial
      contribution was observed for the C4-methyl group on the 4-aminobutanoic acid
      subunit and its removal resulted in a 7 times reduction in DNA cleavage
      efficiency. Little effect for the C3-hydroxyl and C2-methyl substituents on the 4
      aminobutanoic acid subunit was observed (0-2.5 times) and even their inversion
      of stereochemistry had little impact on DNA cleavage efficiency or selectivity.
      Notably, the magnitude of the previously unappreciated L-threonine substituent
      contribution to the DNA cleavage efficiency and on the ratio of double to single
      strand DNA cleavage events is the largest effect observed to date including the
      well recognized disaccharide potentiation (6 times) of the DNA cleavage
      properties. Consequently, the past role and relative importance of the L
      threonine subunit and substituent has been underestimated. Moreover, the
      cumulative effect of the two important linker chain substituents clearly
      illustrate that the functional role of this domain is much more important than
      its simply serving as a linker.

PMID- 8564422
TI  - Pleasant odors and congruency: effects on approach behavior.
AB  - Ninety subjects between the ages of 18 and 35 viewed 24 slides when the testing
      room was scented with no odor or one of two pleasant scents (baby powder or
      chocolate). Six slides were of babies, six were of chocolate items and 12 were
      control slides of pine trees or the Orient. In pilot testing the chocolate slides
      were rated as being congruent with the chocolate scent and incongruent with the
      baby powder scent; the baby slides were rated as being congruent with the baby
      powder scent and incongruent with the chocolate scent. Subjects viewed the slides
      at their own pace while a computer recorded how long each slide was viewed.
      During a second viewing, subjects rated the slides and answered questions about
      their own mood and health. Congruency did not play a role in the findings.
      Pleasant odors had certain effects compared to no odor (i.e. longer looking time,
      better mood and lower hunger ratings), while other effects were related to
      specific odors (i.e. arousal was highest in the chocolate condition and there
      were fewer health symptoms reported in the baby powder condition). These findings
      suggest that pleasant odors may have some general effects due to their hedonic
      value, while associations individuals have with particular pleasant odors may
      influence other variables.

PMID- 8564423
TI  - Evidence that a Gq-protein mediates excitatory odor transduction in lobster
      olfactory receptor neurons.
AB  - Non-hydrolysable analogs of GTP and GDP alter odor-evoked inward and outward
      currents in voltage-clamped cultured lobster olfactory receptor neurons. Currents
      of both polarities are pertussis and cholera toxin-insensitive. Antibodies
      directed against the alpha subunits of G(olf), G(o), G11, an internal Gq
      sequence, the common carboxyl terminal sequence of Gq and G11 (anti-Gq/11), and
      the transducin beta subunit, fail to perturb the outward current, but anti-G(o)
      and anti-Gq/11 selectively block the inward current. Anti-Gq/11 immunolabels a
      band of approximately 45 kDa by Western blot analysis, but the anti-G(o)
      immunolabeling is non-specific. These results suggest that the excitatory
      olfactory signalling pathway that leads to an odor-evoked inward current may be
      coupled via a member of the Gq family, while the odor-evoked outward current is
      transduced by a different G protein.

PMID- 8564424
TI  - Reliability and validity of electrogustometry and its application to young and
      elderly persons.
AB  - Electrogustometric-threshold assessment demonstrated excellent test-retest
      reliability, good bilateral correspondence and age-related differences. Tactile
      and stimulus-related descriptors of the sensation elicited at detection
      threshold, as well as a lack of correlation between whole-mouth chemical
      thresholds and anterior tongue electrogustometric thresholds, raise questions for
      future research.

PMID- 8564425
TI  - Electrocortical and autonomic alteration by administration of a pleasant and an
      unpleasant odor.
AB  - The present study was designed to investigate whether there is a consistent
      response in ongoing EEG due to repetitive olfactory stimulation. Two odors of
      different hedonic quality were presented bilaterally to five male subjects at
      suprathreshold levels. A room-air blank served as the control stimulus. Each odor
      was presented six times to each subject in each of three sessions.
      Electrocortical activity, heart rate, skin conductance and breathing cycle were
      recorded continuously. EEG variables assessed were difference scores of absolute
      power in the frequency bands theta, alpha 1, alpha 2 and beta 1 at eight
      locations. Phenylethyl alcohol was rated pleasant, while valeric acid was judged
      unpleasant. Within 8 s after stimulus release, valeric acid increased alpha 2
      power, whereas phenylethyl alcohol did not. No further frequency bands were
      affected by olfactory stimulation. These findings suggest that smelling an
      unpleasant odor leads to a cortical deactivation.

PMID- 8564426
TI  - The emotional distinctiveness of odor-evoked memories.
AB  - A modified paired-associate learning paradigm was used to test whether odors or
      verbal odor labels evoked more emotional memories. Subjects were presented with
      emotionally positive and negative paintings (to-be-remembered items) in
      association with positive and negative odors and odor labels. Painting recall and
      associated emotional experience were tested after 48 h. Odor-evoked memories were
      found to be more emotional than verbally cued memories on a variety of measures.
      Moreover, if the cue for recall (odor or label) was hedonically congruent with
      the painting to be remembered, memory for original emotional experiences was
      enhanced. The findings are discussed within a general cognitive framework and
      implications for using odors to dissociate the emotional and representational
      aspects of memory are addressed.

PMID- 8564427
TI  - Propylthiouracil tasting: determination of underlying threshold distributions
      using maximum likelihood.
AB  - The ability to taste low concentrations of propylthiouracil (PROP) and related
      bitter compounds is heritable. The current analysis determines whether the
      distribution of PROP taste thresholds is consistent with an additive or a
      dominant mode of Mendelian transmission. To that end, the lowest concentration of
      PROP detectable was determined for 1015 subjects and models of bi- or tri-modal
      distributions of PROP taste thresholds were tested. The model with the greatest
      likelihood had three distributions and followed an additive model of PROP taste
      sensitivity if the variances associated with the distributions were assumed to be
      equal. However, if the taste thresholds were transformed to remove skewness, or
      if the variances were unequal, then three- or two-distribution models were
      equally likely. Resolution of the mode of inheritance for bitter taste perception
      awaits additional family studies and the characterization of the molecular basis
      of taste perception for these bitter compounds.

PMID- 8564428
TI  - Possible active site of the sweet-tasting protein thaumatin.
AB  - Epitopes on thaumatin and monellin were studied using the PEPSCAN-technology. The
      antibodies used were raised against thaumatin. Only antibodies that, in an ELISA,
      both recognized thaumatin and monellin were used in the PEPSCAN-analyses. On
      thaumatin two major overlapping epitopes were identified. On monellin no epitopes
      could be identified. The identified epitope region on thaumatin shares structural
      features with various peptide and protein sweeteners. It contains an aspartame
      like site which is formed by Asp21 and Phe80, tips of the two extruding loops
      KGDAALDAGGR19-29 and CKRFGRPP77-84, which are spatially positioned next to each
      other. Furthermore, sub-sequences of the KGDAALDAGGR19-29 loop are similar to
      peptide-sweeteners such as L-Asp-D-Ala-L-Ala-methyl ester and L-Asp-D-Ala-Gly
      methyl ester. Since the aspartame-like Asp21-Phe80 site and the peptide-sweetener
      like sequences are also not present in non-sweet thaumatin-like proteins it is
      postulated that the KGDAALDAGGR19-29- and CKRFGRPP77-84 loop contain important
      sweet-taste determinants. This region has previously not been implicated as a
      sweet-taste determinant of thaumatin.

PMID- 8564429
TI  - The perception of saltiness is eliminated by NaCl adaptation: implications for
      gustatory transduction and coding.
AB  - The tastes of salts to humans are complex. NaCl is the most purely salty of all
      salts, but even this stimulus tastes sweet at low concentrations and somewhat
      sour at mid-range intensities. Other salts taste significantly sour or bitter in
      addition to salty. Previous studies have shown that the saltiness of simple
      halide salts is reduced by adaptation to NaCl, suggesting that a single mechanism
      might be responsible for the salty taste of these stimuli. In
      electrophysiological studies in rodents, the response to NaCl is reduced by
      application to the tongue of the Na(+)-channel blocker amiloride. Organic Na+
      salts are more heavily dependent on this amiloride-sensitive transduction
      component than NaCl, and are generally less salty and more sour. In order to
      investigate the relationship between NaCl saltiness and that evoked by other
      salts, we adapted the tongue to distilled H2O and to 0.1 M NaCl and obtained
      direct magnitude estimates of the taste intensity of 15 organic and inorganic
      Na+, Li+, K+ and Ca2+ salts, matched for total intensity. Subjects divided these
      magnitude estimates among the component taste qualities. Adaptation to NaCl
      abolished the taste of NaCl and LiCl, and eliminated the saltiness of all other
      salts. The magnitude estimates of the bitterness and sourness of many salts
      increased after NaCl adaptation. Since recent biophysical data suggest that
      adaptation in taste receptors may involve whole-cell mechanisms, we propose that
      saltiness is reduced by NaCl adaptation because it originates in the subset of
      taste receptors responsive to NaCl. This implies that saltiness is coded within
      the CNS in cells whose receptive fields include the NaCl-sensitive receptor cells
      and that the degree to which any salt tastes salty is determined by its ability
      to drive these receptors. This model proposes, for example, that KCl has a salty
      component because it stimulates some of the same receptor cells as NaCl, even
      though the transduction mechanisms for KCl are different than those engaged by
      NaCl. Adaptation to NaCl blocks the saltiness of KCl and other salts because they
      stimulate NaCl-sensitive receptor cells.

PMID- 8564430
TI  - Amiloride is an ineffective conditioned stimulus in taste aversion learning.
AB  - The present study demonstrated that 100 microM amiloride serves as an ineffective
      conditioned taste stimulus in a taste aversion paradigm. Even if amiloride has a
      detectable taste, it's unlikely that its behavioral effects in salt mixture
      experiments are due to its inherent taste quality.

PMID- 8564431
TI  - Analysis of odor discrimination by multidimensional scaling at different
      temperatures.
AB  - Discrimination of odorants by the turtle olfactory bulb at 25 degrees and 37
      degrees C was examined by the cross-adaptation technique and analysed by
      multidimensional scaling. Analysis by multidimensional scaling suggests that at
      25 degrees C odorants are grouped according to their odor qualities in the turtle
      olfactory system. At 37 degrees C, the cluster formation of odorants, which have
      a similar odor quality,such as minty and floral alcohol odorants and molecular
      structure, in the plot of multidimensional scaling was poor, indicating that the
      ability of odor grouping according to their odor qualities was low at 37 degrees
      C.

PMID- 8564432
TI  - Evolution of the sweetness receptor in primates. I. Why does alitame taste sweet
      in all prosimians and simians, and aspartame only in Old World simians?
AB  - In the order Primates the responses to sucrose, alitame and aspartame were
      ascertained. All primates tested to date like sucrose and prefer this sweet
      substance to tap water. The artificial dipeptide aspartame was found to be not
      sweet in Prosimii and Platyrrhini (New World monkeys). Only the Cercopithecoidea
      (Old World monkeys) and Hominoidea (apes and humans) show the same response to
      aspartame and to sucrose. In contrast, all primates tested so far prefer alitame,
      another artificial dipeptide sweetener, which is structurally closely related to
      aspartame. This phylogenetic difference is consistent with the existence in
      catarrhine primates of a sweetness receptor containing two differently located
      hydrophobic recognition sites, one for the hydrophobic binding site of alitame,
      the other for the hydrophobic binding site of aspartame. On the basis of these
      results, it is suggested that the alitame-related hydrophobic recognition site,
      which is found in the sweetness receptor of all primates, could be a requisite
      for the interaction of the receptor with sucrose, while the aspartame-related
      hydrophobic recognition site, which is found exclusively in the sweetness
      receptor of Old World simians, could have been a crucial factor in the
      improvement in detection or selection of sucrose in foods, so favouring the
      mental development of these simians and maybe the emergence of humans.

PMID- 8564433
TI  - Functional equivalence of the two sides of the human nose in odor detection.

PMID- 8564434
TI  - NIST SRM 1945, whale blubber, NIST SRM 1974a, organics in mussel tissue, and NIST
      SRM 1941a, organics in marine sediment as certified reference materials for
      polychlorinated dioxins and furans in marine ecosystems.
AB  - Few natural matrix Standard Reference Materials are available for the validation
      of analytical methods measuring polychlorinated dioxins and furans (PCDDs and
      PCDFs) in marine ecosystems. The concentrations of PCDDs and PCDFs in NIST SRM
      1945, SRM 1974a, and SRM 1941a are of interest because the analysis of marine
      mammal, mussel tissues and sediments have become important tools in the
      determination of organochlorine contamination of the environment. Because these
      SRMs have been demonstrated to be homogenous for other organic contaminants, they
      would be expected to be reliable standards for validation of polychlorinated
      dioxins and furans in marine mammals, mussels and sediments as well.

PMID- 8564435
TI  - Sources of PCDD/PCDF and impact on the environment.
AB  - PCDD/PCDF can be formed in a variety of industrial and thermal processes.
      Especially the combustion sources contribute to the ambient air levels. In
      addition to the well-investigated emissions from municipal waste incinerators
      dioxins were measured in the flue gases of other thermal emitters. It was found
      that some recycling plants can emit high concentrations of PCDD/PCDF. Ambient air
      concentrations monitored over several years have shown a clear seasonal trend
      with higher PCDD/PCDF levels in winter and lower concentrations during summer.
      Thus, results from short-term measurements cannot be used to calculate annual
      means for ambient air concentrations or deposition rates. Dioxins, once
      concentrated in sewage sludge and compost can re-enter the environment when these
      "reservoirs" are applied onto agricultural and horticultural soils.

PMID- 8564436
TI  - Molecular cell biology and physiology of solute transport.

PMID- 8564437
TI  - Pharmacology and therapeutics.

PMID- 8564438
TI  - Stretch-induced parathyroid hormone-related peptide gene expression: implication
      in the regulation of myogenic tone.

PMID- 8564439
TI  - The electroneutral sodium-(potassium)-chloride co-transporter family: a journey
      from fish to the renal co-transporters.

PMID- 8564440
TI  - Water channels.
AB  - The aquaporin water channels are expressed in various fluid-transporting
      epithelia. Physiological and genetic investigations have revealed that aquaporin
      channel-like intrinsic protein is expressed in numerous tissues, but its
      significance in water transport physiology is unclear. It has been shown that
      aquaporin-collecting duct is a vasopressin-responsive water channel, and that it
      is regulated by a membrane shuttle mechanism. Three unique models for a water
      pore have been presented but further studies will be required to verify them. New
      aquaporin members have been isolated and their discrete localization may reflect
      their specific physiological roles.

PMID- 8564441
TI  - Renal chloride-bicarbonate exchangers.
AB  - This review discusses the molecular identities and functional properties of
      sodium-independent Cl(-)-HCO3- exchangers in the kidney. The main sites of renal
      Cl(-)-HCO3- exchange are in the intercalated cells of the collecting duct. The
      function of Cl(-)-HCO3- exchange is to provide a pathway for base efflux to
      balance the ATP-driven H+ efflux in cells that carry out transcellular net
      transport of H+. In the alpha-intercalated cell, which secretes H+ into the
      lumen, there is now excellent evidence that the basolateral Cl(-)-HCO3- exchanger
      is an N-terminal truncated form of the erythrocyte anion exchanger 1 (band 3)
      protein. In the beta-intercalated cell, which secretes HCO3-, it is well
      established that there is a Cl(-)-HCO3- exchanger in the apical membrane.
      Functional, immunocytochemical, and biochemical evidence indicate that the apical
      Cl(-)-HCO3- exchanger is not a product of the anion exchanger 1 gene. The
      identity of this protein remains uncertain.

PMID- 8564442
TI  - The structure, regulation and pathophysiology of potassium channels.
AB  - Potassium channels are membrane proteins that allow the passive diffusion of
      potassium down its electrochemical gradient. They play a critical role in many
      cellular processes and have, therefore, been extensively studied. Over the past
      several years, the molecular structures of several types of potassium channels
      have been elucidated. This review investigates the most recent findings regarding
      the structure, regulation and pathophysiology of potassium channels.

PMID- 8564443
TI  - Facilitative glucose transport proteins and sodium-glucose co-transporters in the
      kidney.
AB  - Cloning studies have characterized a large gene family of facilitative glucose
      transporters that are expressed in a tissue-specific manner, and at least two
      sodium-glucose co-transporters in brush-border membranes of intestinal and renal
      epithelia. These different transporters play specific roles in glucose transport
      and homeostasis because of their different tissue distribution, kinetic
      properties, and regulation of function. This review discusses recent advances in
      the study of glucose transporters and the regulation of their expression in the
      normal kidney and in diabetes.

PMID- 8564444
TI  - Amino acid transporters.
AB  - This review focuses on two main aspects of amino acid transport. One aspect is
      the role of the basic amino acid transporter gene in causing cystinuria, its
      functional properties, and its potential transport functions. The other is the
      regulation of amino acid transporters at the levels of information processing and
      cellular organization.

PMID- 8564445
TI  - Regulation of sodium transport.
AB  - Sodium excretion, one of the most important homeostatic functions of the body, is
      modulated by a number of autocrine, paracrine and endocrine factors that act by
      altering the balance in complex signalling networks in tubular cells. It is
      probable that most, if not all, integral membrane proteins that transport sodium
      are regulated by signals from such networks. The activity of the sodium
      transporting proteins may be modified by the phosphorylation/dephosphorylation
      process, or by other means of protein modification. The rate of transport may
      also be dynamically regulated by other post-translational processes, such as
      recruitment of the sodium-transporting proteins to the membrane. The
      identification of the signalling networks that regulate the tubular sodium
      transporters and of the regulatory sites in these sodium-transporting proteins
      will bring further insights into the pathophysiology of salt-sensitive
      hypertension.

PMID- 8564446
TI  - Regulation of vesicular transport by GTP-binding proteins.
AB  - Intracellular protein trafficking occurs in a series of transport vesicles.
      Vesicle trafficking is regulated both by heterotrimeric and monomeric GTP-binding
      proteins (G proteins). Recent studies have explored effector systems used by
      heterotrimeric G proteins and by monomeric ADP-ribosylation factor G proteins for
      regulation of vesicle budding. New members of the Rab monomeric G protein family
      have been identified in polarized cells and new evidence confirms the function of
      Rab proteins in vesicle targeting. From these data we can begin to reconstruct
      the signal transduction pathways that regulate intracellular transport.

PMID- 8564447
TI  - Are angiotensin-converting enzyme inhibitors the renal protective
      antihypertensive drugs of choice?

PMID- 8564448
TI  - Corticosteroid hypertension.
AB  - Over the past year, the focus in corticosteroid hypertension has been on the
      cloning of the enzyme 11 beta-hydroxysteroid dehydrogenase, and the demonstration
      of a variety of mutations or deletions in the sequence coding for this enzyme in
      the syndrome of apparent mineralocorticoid excess. This syndrome is the third
      single-gene cause of human hypertension to be characterized, with glucocorticoid
      remediable aldosteronism (1992) and Liddle's syndrome (1994). The three
      conditions are characterized by inappropriate control of aldosterone secretion
      (glucocorticoid remediable aldosteronism), sodium retention (Liddle's syndrome)
      or aldosterone action (apparent mineralocorticoid excess), and underline a
      potential role of an aldosterone: salt imbalance in mineralocorticoid
      hypertension. No comparable mechanisms of hypertension following glucocorticoid
      receptor occupancy have been documented to date.

PMID- 8564449
TI  - Hypertension in postmenopausal women: pathophysiology and management.
AB  - Hypertension, particularly systolic hypertension, afflicts over 50% of
      postmenopausal women and is an important risk factor for cardiovascular disease
      in this group. Hormone replacement therapy with estrogen or an estrogen/progestin
      combination does not alter blood pressure but has beneficial effects on other
      cardiovascular risk factors, so should be considered in all postmenopausal women
      unless contraindicated.

PMID- 8564450
TI  - Hypertension after cardiac transplantation: pathophysiology and management.
AB  - This article reviews the current state of knowledge concerning cyclosporine A
      induced hypertension after heart transplantation, its pathophysiology and
      management. The hypothesis is presented that a common molecular mechanism
      mediates both the immunosuppressive and the hypertensive actions of cyclosporine.
      The calcium-calmodulin dependent phosphatase, calcineurin, is the common cellular
      target mediating the salient immunosuppressive effects of both cyclosporine A and
      FK506. Calcineurin is even more plentiful in nonlymphoid tissues such as the
      nervous system, muscle, and kidney. Because these are the main target sites for
      cyclosporine A-induced toxicity, it has been hypothesized recently that
      inhibition of calcineurin mediates cyclosporine A-induced toxicity. This
      hypothesis is supported by increasing experimental evidence, at both the whole
      animal and cellular levels, indicating that the toxicity profile of cyclosporine
      A is duplicated by FK506 but not by rapamycin, a structural analog of FK506 which
      is a potent immunosuppressive agent but has no effect on calcineurin. Recent
      multicenter trials demonstrate that in the clinical setting the hypertensive and
      other side effects of cyclosporine A are duplicated by FK506. The clinical
      toxicity of rapamycin is as yet unknown.

PMID- 8564451
TI  - Orthostatic hypotension: epidemiology, pathophysiology and management.
AB  - Orthostatic hypotension is characterized by low upright blood pressure levels and
      symptoms of cerebral hypoperfusion. Whereas orthostatic hypotension is
      heterogeneous, correct pathophysiologic diagnosis is important because of
      therapeutic and prognostic considerations. Although therapy is not usually
      curative, it can be extraordinarily beneficial if it is individually tailored.
      Management of the Shy-Drager syndrome (multiple-system atrophy) remains a
      formidable challenge.

PMID- 8564452
TI  - Benign prostatic hyperplasia: pathophysiology and pharmacological treatment.
AB  - Recent studies have confirmed that alpha-blocker therapy and antihormonal therapy
      are effective and safe treatment modalities in patients with symptomatic benign
      prostatic hyperplasia. New data suggest that the clinical response to medical
      therapy lasts for at least 3 years without any increase in side effects during
      this period.

PMID- 8564453
TI  - Hypertension in autosomal dominant polycystic kidney disease.
AB  - Hypertension occurs frequently in autosomal dominant polycystic kidney disease.
      Increased activity of the renin-angiotensin system contributes to the development
      and maintenance of hypertension before the development of renal failure.
      Angiotensin-converting enzyme inhibitors are indicated for treatment of
      hypertension before the development of renal failure, but in severe renal failure
      these agents may cause further deterioration in renal function. Treatment of
      hypertension may not retard the progression of renal failure but is necessary for
      the prevention of cardiovascular disease.

PMID- 8564454
TI  - Choice and constraints in floodplain occupation: the influence of structural
      factors on residential location in peninsular Malaysia.
AB  - In Peninsular Malaysia 'structural' factors are found to influence strongly
      people's persistent occupation of floodplains. Thus, despite a high level of
      flood hazard awareness, a high level of pessimism and a high level of expectation
      of future floods, poorer individuals seldom attempt to leave for more
      advantageous locations but are instead trapped in their present locations by
      structural factors such as poverty, low residential and occupational mobility,
      low educational attainment, traditional land inheritance, government aid, and
      government disaster preparedness, relief and rehabilitation programmes. These
      forces exert a strong influence upon individuals and largely control their choice
      of residential location in response to flood hazards, thereby reinforcing the
      persistent occupation of floodplains. Structural factors such as landlessness,
      rural-urban migration, floodplain encroachment and squatting are also highly
      influential in leading people to move. Even for those who move, structural
      factors have largely confined their choice of residential location to urban
      floodplains.

PMID- 8564455
TI  - The American print news media 'construction' of five natural disasters.
AB  - In 1985, five international 'natural' disasters received prominent print news
      media coverage in the United States. Content analyses of selected print news
      media accounts of these five disasters were conducted. The purported evidence of
      alleged cause-effect relationships describing and explaining these disasters as
      'objective' realities was evaluated in the light of the subjective selection of
      explanatory factors, themes, frameworks, and value assumptions which underlie the
      media's analysis and 'construction' of these events as 'natural' disasters.
      Analysis of the American print news media coverage of these disasters indicated
      an emphasis upon the dramatic, descriptive, climatological or geological
      qualities of these events rather than upon causal explanations emphasizing the
      role of human acts or omissions in the development of these disasters. The print
      news media 'constructed' these events as 'natural' disasters despite clear
      evidence of their hybrid, natural-human origins.

PMID- 8564456
TI  - Effective emergency management: reconsidering the bureaucratic approach.
AB  - The command and control approach is compared with the Emergent Human Resources
      Model (EHRM) approach to emergency management. Four decades of systematic
      research shows that a rigid, bureaucratic command and control approach to
      emergency management generally leads to an ineffective emergency response.
      Previous studies and our own research suggest that flexible, malleable, loosely
      coupled, organizational configurations can create a more effective disaster
      response.

PMID- 8564457
TI  - Evaluation of long-term community recovery from Hurricane Andrew: sources of
      assistance received by population sub-groups.
AB  - Two three-stage cluster surveys were conducted in South Dade County, Florida, 14
      months apart, to assess recovery following Hurricane Andrew. Response rates were
      75 per cent and 84 per cent. Sources of assistance used in recovery from
      Hurricane Andrew differed according to race, per capita income, ethnicity, and
      education. Reports of improved living situation post-hurricane were not
      associated with receiving relief assistance, but reports of a worse situation
      were associated with loss of income, being exploited, or job loss. The number of
      households reporting problems with crime and community violence doubled between
      the two surveys. Disaster relief efforts had less impact on subjective long-term
      recovery than did job or income loss or housing repair difficulties. Existing
      sources of assistance were used more often than specific post-hurricane relief
      resources. The demographic make-up of a community may determine which are the
      most effective means to inform them after a disaster and what sources of
      assistance may be useful.

PMID- 8564458
TI  - Rehabilitation planning for flood affected areas of Thailand: experience from
      Phipun District.
AB  - Floods are common in Thailand. A flood in the southern part of the country in
      1988 was of unprecedented magnitude. Several villages and vast tracts of
      agricultural land were covered with mud slides washed away from deforested hills.
      Rehabilitation of the affected areas, a task which required complex planning, was
      a challenge for the District Development Committee (DDC), which is the local
      level planning body. The Committee encountered several problems, including
      inability to use the existing data base and lack of accurate information, human
      resources, adequate funds and coordination among agencies. Unable to cope with
      the new challenges, the DDC resorted to conventional planning which failed to
      address the problems caused by the flood. Guidelines should be formulated to
      strengthen district level planning for rehabilitation after a disaster.

PMID- 8564459
TI  - The role of the Zairian Health Services in the Rwandan refugee crisis.
AB  - In July 1994, a stream of Rwandan refugees entered the southern part of North
      Kivu Region, Zaire. The public health consequences of this crisis for the host
      population and health services have not been analysed up to now. The lack of
      human and financial resources did not prevent Zairian health structures and
      personnel from taking care of the many refugees settled outside the camps,
      following their arrival. The public health consequences of the crisis for the
      local population should be considered an integral part of the disaster.

PMID- 8564460
TI  - Aid under fire: redefining relief and development assistance in unstable
      situations, Wilton Park (UK) 7-9 April, 1995.

PMID- 8564461
TI  - A 'disaster' continuum?

PMID- 8564462
TI  - The evolution of isocortex.
AB  - There are several reasons why we lack detailed and comprehensive theories of how
      isocortex evolved in the various lines of mammalian evolution. Although current
      methods allow cortical areas to be defined with a high degree of assurance, few
      taxa have been studied in detail, and even the most-studied taxa are incompletely
      understood. In addition, concepts persist from early studies, based on limited
      data, that confound current theories, and some theories of isocortical evolution
      have been based on questionable premises. Nevertheless, some conclusions are
      clearly supportable. Early mammals had small brains with proportionately little
      isocortex. Mammals with larger brains and proportionately more isocortex evolved
      in several lines of descent. All mammals appear to have roughly 20 cortical
      areas, 'the organs of the brain', in common as retentions from an early ancestor,
      with primary and secondary sensory fields occupying much of cortex. Some of these
      cortical areas have been greatly modified in some taxa to become significantly
      expanded in size, highly laminated structurally, or both. Numbers of areas have
      increased independently in several branches of mammalian evolution, and the
      functioning of large brains may be enhanced by having more subdivisions. Finally,
      over many generations new areas may emerge from old by the formation of
      functionally distinct modules within areas, followed by the fusion of modules to
      ultimately form separate ones.

PMID- 8564463
TI  - The thalamus of reptiles and mammals: similarities and differences.
AB  - Certain aspects of thalamic organization in reptiles and mammals are reviewed.
      Features shared by the dorsal thalamus of reptiles and that of mammals include
      projection to the telencephalon, specific and non-specific non-telencephalic
      afferents, and input from the thalamic reticular nucleus. Differences between the
      dorsal thalamus of reptiles and that of mammals are the absence of reciprocal
      telencephalic efferents to the dorsal thalamus and lack of local circuit neurons
      in reptiles (with the exception of the dorsal geniculate complex in turtles) and
      their presence in mammals. A thalamic reticular nucleus is present in both
      reptiles and mammals. In both of these classes of vertebrates, this neuronal
      aggregate surrounds the dorsal thalamus along its lateral surface, projects to
      the dorsal thalamus, and is organized into sectors. In one group of reptiles,
      Caiman crocodilus, the sole reptilian group in which immunocytochemical features
      have been investigated in detail, the reticular nucleus contains at least three
      neuronal subpopulations: neurons immunoreactive for glutamic acid decarboxylase
      (GAD); neurons immunoreactive for parvalbumin; and cells that are not
      immunoreactive for parvalbumin or, probably, GAD. On the other hand, the
      reticular nucleus of mammals contains a single population of neurons
      immunoreactive for GAD, gamma amino butyric acid, and parvalbumin.

PMID- 8564464
TI  - The dorsal thalamus of jawed vertebrates: a comparative viewpoint.
AB  - In anamniotes, the dorsal thalamus comprises: (1) a caudal division, the
      collothalamus, which receives its predominant input from the midbrain roof and
      projects ipsilaterally to the telencephalon, predominantly to the striatum, and
      (2) a rostral division, the lemnothalamus, which predominantly receives a direct
      retinal (lemniscal) input and projects bilaterally to the telencephalon,
      predominantly to the pallium. In amniotes, collothalamic nuclei relay visual,
      auditory, and somatosensory-multisensory inputs from the midbrain roof to the
      ipsilateral telencephalon, terminating in both striatum and pallium. For example,
      the collothalamic visual nuclei consist of the LP-pulvinar complex in mammals and
      nucleus rotundus in diapsid reptiles, birds, and turtles. Among amniotes, the
      latter nuclei are homologous to each other as discrete nuclei, as are the
      collothalamic auditory and collothalamic somatosensory-multisensory nuclei.
      Lemnothalamic nuclei (and nuclear groups) in amniotes predominantly (and/or
      plesiomorphically) receive lemniscal inputs; some project to the telencephalon
      bilaterally, and most, in contrast to collothalamic nuclei, do not project to the
      striatum. In mammals, the lemnothalamic nuclei include most of those in the
      anterior, medial, intralaminar, and ventral nuclear groups and the dorsal lateral
      geniculate nucleus. In diapsid reptiles, they include the dorsomedial and
      dorsolateral anterior nuclei and the dorsal lateral optic nucleus; comparable
      nuclei are present in birds and turtles, with birds additionally having a
      discrete somatosensory lemniscal relay nucleus. These lemnothalamic nuclei in
      each amniote radiation are homologous as a field to the lemnothalamus (i.e.,
      nucleus anterior) in anamniotes. Both divisions of the dorsal thalamus were
      elaborated to some degree in the common ancestral amniote stock. A further major
      elaboration of the lemnothalamus characterized the ancestral stock of mammals and
      may have been one of the key events in early mammalian evolution. Birds have
      independently, to a lesser degree, elaborated the lemnothalamus.

PMID- 8564465
TI  - The limbic system of tetrapods: a comparative analysis of cortical and amygdalar
      populations.
AB  - Recent studies of the limbic system of tetrapods have made data available that
      challenge some of the long-held tenets of forebrain evolution. Using the basic
      principle of parsimony--that the best hypotheses concerning homologies are those
      requiring the fewest number of evolutionary changes--we have reevaluated
      comparisons of tetrapod limbic systems. Given the current data, the following
      points appear to be justified: (1) the common ancestors of reptiles and mammals
      had a well-developed limbic system in which the basic subdivisions and
      connections of the amygdalar nuclei were established; (2) the ventral part of the
      lateral pallium in amphibians appears to be a single structure which corresponds
      to at least four areas in reptiles: centromedial DVR, ventral anterior amygdala,
      lateral amygdala, and part of the lateral cortex; (3) the medial pallium in
      amphibians appears to be homologous with the dorsal and medial cortices in
      reptiles and with the general and hippocampal cortices in mammals: (4) the
      cortical targets of the main olfactory bulb in reptiles and mammals appear to be
      homologous, and their common ancestor probably had a corresponding olfactory
      pallial field; (5) the targets of the accessory olfactory bulb in amphibians,
      reptiles, and mammals appear to be homologous, with the exception of nucleus
      sphericus in reptiles, which lacks an obvious homologue in non-reptiles.

PMID- 8564466
TI  - Neurotransmitter organization and connectivity of the basal ganglia in
      vertebrates: implications for the evolution of basal ganglia.
AB  - The basal ganglia in modern mammals, birds and reptiles (i.e. modern amniotes)
      are very similar in connections and neurotransmitters, suggesting that the
      evolution of the basal ganglia in amniotes has been very conservative. For
      example, the basal ganglia in all amniotes possess a dorsal striatum containing
      two main populations of projection neurons, substance P-containing (SP+) and
      enkephalin-containing (ENK+) neurons, which have major projections to the dorsal
      pallidum and the tegmentum (ventral tegmental area and substantia nigra, or
      VTA/SN). The VTA/SN, in turn, has a major dopaminergic (DA+) projection to the
      striatum in all amniotes. In this paper, we review these data on the basal
      ganglia in amniotes and note points of similarity and difference in the
      functional circuitry of the basal ganglia among amniotes. In addition, we review
      recent findings on the neurotransmitter organization and connectivity of the
      basal ganglia in amphibians and fishes, with the goal of assessing whether a
      basal ganglia showing the same basic features as in amniotes is observed in
      anamniotes. Published data indicate that in at least two groups of fishes
      (cartilaginous fishes and lungfishes) and apparently in amphibians, the basal
      ganglia is present and consists of a distinct striatum and pallidum. The striatum
      of amphibians, cartilaginous fishes, and lungfishes contain SP+ and ENK+ neurons
      that seem to project to the pallidum as well as to a brainstem cell group that
      appears comparable to the VTA/SN of amniotes. Data for ray-finned fishes also
      suggest the presence of a striatum containing SP+ and ENK+ neurons that projects
      to VTA/SN-like brainstem cell group. In the basal ganglia of ray-finned fishes,
      however, a distinct pallidum had not been identified. Finally, the brainstem cell
      group receiving striatal input in all anamniotes contains DA+ neurons that seem
      to project to the striatum. The present analysis suggests that a rudimentary
      basal ganglia was already present in the brain of the ancestral jawed
      vertebrates. This rudimentary basal ganglia likely consisted of a striatum and a
      pallidum, and the striatum probably already possessed the same basic connections
      and some of the same basic cell types as the basal ganglia of modern jawed
      vertebrates.

PMID- 8564467
TI  - Comparative aspects of forebrain organization in the ray-finned fishes:
      touchstones or not?
AB  - The comparative interpretation of forebrain organization of the ray-finned fishes
      presents a number of challenges. The telencephalon develops by an eversion
      process, and much of its surface is ventricular rather than pial. A topological
      map of the ventricular surface shows that the area ventralis (presumed
      subpallium) is bordered dorsally by the dorsomedial (DM) zone of the area
      dorsalis, which is, in turn, bordered by the olfactory-recipient dorsoposterior
      (DP) zone of the area dorsalis. Within the diencephalon small dorsal and ventral
      thalami and a large group of migrated nuclei assigned to the posterior tuberculum
      (but of uncertain status) are present. Both the dorsal thalamus and the migrated
      nuclei of the posterior tuberculum project to the telencephalon. A review of the
      known connections of the four major zones of the area dorsalis together with
      their topological positions leads to the following tentative interpretations.
      Zone DP is homologous to the primary olfactory cortex. There is not enough
      information concerning the dorsodorsal zone (DD) to speculate on its comparative
      relationships. Zone DM is a limbic-like area lying between the subpallium and the
      olfactory pallium and is possibly homologous to the pallial amygdala. The
      dorsolateral zone (DL) displays a pattern of connectivity with the cerebellum and
      the optic tectum suggesting a possible homology with non-olfactory, non-limbic
      pallial areas. Caveats are raised concerning the above interpretations of DM and
      DL. One or both of them may have evolved independently of the telencephalic zones
      in tetrapods and may thus represent examples of homoplasy.

PMID- 8564468
TI  - The forebrain of gnathostomes: in search of a morphotype.
AB  - A morphotype of the forebrain of gnathostomes, i.e. those characters that must
      have been present in the forebrain of ancestral gnathostomes, was generated by
      using out-group analysis to identify the shared primitive characters present in
      the forebrains of extant gnathostomes. The nature of morphotypes and the steps in
      generating a morphotype are described. Because hypotheses of phylogenetic
      relationships profoundly affect the resulting morphotype, current hypotheses of
      gnathostome interrelationships are reviewed, and particular attention is paid to
      the problematic relationships of lobe-finned fishes. Ontogenetic studies provide
      the most common basis for how neural characters are grouped, and a review of the
      developmental literature indicates that gnathostome forebrains are segmented,
      with the diencephalon arising from a rostral parencephalic neuromere, which
      subsequently forms anterior and posterior divisions, and a more caudal
      synencephalic neuromere. Unfortunately, there is no agreement concerning the
      number of segments that form the secondary prosencephalon (telencephalon and
      hypothalamus). For this reason, the characters of the secondary prosencephalon
      must be analyzed in a topological manner. An out-group analysis of the characters
      of the diencephalon of extant gnathostomes reveals that the diencephalon of
      ancestral gnathostomes must have arisen from three segments: an anterior
      parencephalic segment, which gave rise to intermediate, ventrolateral and
      ventromedial thalamic nuclei; a posterior parencephalic segment, which gave rise
      to dorsal and ventral habenular nuclei, anterior, dorsal posterior, dorsal
      central, and, possibly, lateral posterior thalamic nuclei, and posterior
      tubercular nuclei; a synencephalic segment, which gave rise to pretectal nuclei,
      accessory optic nuclei and the nucleus of the medial longitudinal fascicle. The
      pretectal and posterior tubercular regions of ray-finned fishes appear to be
      highly derived, due to extensive cellular proliferations that give rise to
      numerous nuclei. The secondary prosencephalon of ancestral gnathostomes was
      probably divided rostrally into inverted and evaginated cerebral hemispheres,
      with paired olfactory bulbs arising directly from the hemispheres, and caudally
      into preoptic and hypothalamic areas. The cerebral hemispheres likely comprised a
      dorsally situated pallium divided into medial, dorsal and lateral pallial
      formations, as well as an intercalated pallial nucleus situated ventrolateral to
      the lateral pallium, and a ventrally situated subpallium divided medially into
      septal nuclei and a medial amygdalar nucleus and laterally into a corpus
      striatum. Both pallial and subpallial centers of ancestral gnathostomes probably
      received ascending thalamic and posterior tubercular inputs, with telencephalic
      efferent pathways terminating primarily in the hypothalamus, posterior tubercle
      and midbrain tegmentum. An out-group analysis further indicates that some taxa in
      each gnathostome radiation exhibit highly derived telencephalic characters due to
      the independent expansion of one or more pallial formations.

PMID- 8564469
TI  - A segmental morphological paradigm for understanding vertebrate forebrains.
AB  - The idea is presented that modern segmental thinking on the forebrain is best
      conceived of as a scientific paradigm, which is revealing itself to be
      increasingly advantageous for the interpretation of both causal
      developmental/genetic data and pitfall-free morphology. Various related or
      opposed viewpoints are considered briefly, emphasizing their respective
      assumptions with regard to longitudinal and transverse subdivisions.

PMID- 8564470
TI  - Recognition potential latency and word image degradation.
AB  - Ten subjects viewed a stream of meaningless background images in which English
      words occasionally appeared. A subject indicated detection of a word by lifting
      the index finger of the preferred hand. He received payment based on his
      performance. A computer program degraded half of the word images, removing a
      fraction of the lit pixels and replacing them with others that resembled the
      background images. The recognition potential (RP) was recorded from occipital
      electrodes. Degrading the word images increased the peak latency of the RP from
      231 to 266 msec. The 35 msec difference was comparable to the 36 msec reaction
      time (RT) difference. At 395 and 431 msec, RT occurred about 165 msec after the
      RP peak. The results indicated the RP is closely related to a recognition
      process. The study did not resolve whether it is concurrent with that process or
      immediately follows it. The RP's sensitivity to image degradation and its short
      latency make it unlikely that N2 and P3 are concurrent with the recognition
      process.

PMID- 8564471
TI  - Processing of number and gender inflections by French-speaking aphasics.
AB  - This study investigates French-speaking aphasics' sensitivity to gender (of human
      nouns) and number marking in a sentential context. Using a forced picture choice
      task, we tested sentences in which grammatical marking surfaced either on a
      function word or on a content word, within or outside a noun phrase (NP) whose
      gender or number was required to be identified. Ten fluent and 10 nonfluent
      aphasics together with 20 adults without neurological history were tested.
      Results showed that neither group of aphasics presented an across-the-board
      deficit. Nonfluent patients were strongly impaired when marking surfaced on a
      content word outside NP (verbs and adjectives), but their sensitivity to
      grammatical marking was relatively well preserved in the within NP condition
      (determiners and nouns) and for function words in the outside NP condition (the
      copula). Fluent patients showed a specific impairment in dealing with semantic
      gender (as opposed to number information); and their difficulty was exacerbated
      when the information conveyed by the suffix of a content word must be integrated
      into an higher order semantic representation, as in the outside NP condition
      (adjectives). These results are consistent with the view that for both nonfluent
      and fluent aphasics, the functional locus of their impairment lies on a reduction
      in the computational resources available to the language processor, which is more
      severe in the former than in the latter group.

PMID- 8564472
TI  - Auditory speech processing in the left temporal lobe: an electrical interference
      study.
AB  - Auditory syllable discrimination, identification, and comprehension were
      investigated by direct cortical electrical interference in three patients with
      indwelling subdural electrode arrays. Without electrical interference, patients
      performed similarly to matched normal subjects. With electrical interference,
      selective deficits were observed in the posterior superior temporal (PST) lobes
      of all three patients. At specific PST sites, only comprehension was impaired,
      while at proximal sites comprehension and identification were impaired, but
      discrimination remained intact. At a single PST site, all three auditory speech
      functions were impaired. These findings suggest that lower-level auditory speech
      functions can operate independent of higher-level processes, as claimed by
      traditional hierarchical models. However, analysis of discrimination errors
      revealed lexical-semantic and phonological effects, suggesting that higher-level
      functions also influence lower-level processing. These data can be explained by a
      bidirectional processing model, with differentially weighted connections.

PMID- 8564473
TI  - Coherence violations and propositional usage in the narratives of fluent
      aphasics.
AB  - Aphasic patients have been generally assumed to produce coherent narratives,
      despite their numerous surface structure deficits. The current study is designed
      to analyze three types of coherence violations (i.e., information gaps,
      repetitions of propositions, and irrelevant propositions) in the narratives of
      mildly impaired conduction, anomic, and Wernicke's aphasics. Results reveal that
      the three aphasic groups produce qualitatively different patterns of coherence
      violations. It is hypothesized that these coherence violations reflect adaptive
      strategies used by the aphasic patients to compensate for their underlying
      impairments. While the anomic and conduction aphasics appear to compensate for
      surface structure deficits, the Wernicke's aphasics seem to have an underlying
      coherence deficit.

PMID- 8564474
TI  - Prosodic characteristics of speech pre- and post-right hemisphere stroke.
AB  - Case-control studies have shown right hemisphere specialization in the production
      of intonation in speech. We examined spontaneous prosody in audiotapes of
      interviews with a 77-year-old right-handed woman recorded 6 months before and 6
      weeks after she suffered a stroke affecting the right frontotemporo-parietal
      regions and the right basal ganglia. Post-stroke, the patient had a normal Mini
      Mental Status Examination Score of 29, hemispatial neglect, and impairments in
      the comprehension of facial expression and prosody. Self-rated mood was within
      normal limits. We compared beginning, peak, and ending fundamental frequencies
      (fo) in breath groups, the timing of these fo changes, rate of speech, pause
      duration, and breath-group duration. We found that post-stroke, the patient had a
      more restricted fo contour, no changes in the timing of peak fo, an increased
      rate of speech, less variability in pause duration, and no changes in breath
      group duration.

PMID- 8564475
TI  - Phonological and lexical coding in verbal short-term memory and learning.
AB  - A patient with selective auditory phonological coding defect is described. He
      also showed a defective auditory verbal short-term memory but could learn lists
      of words flawlessly, thus closely resembling patients with pure short-term memory
      defects. We argue that the patient's functional defect could be conceived as a
      capacity limitation of the phonological short-term store. An experimental
      evaluation of his verbal short- and long-term memory performances allows a
      discussion of the interaction of phonological and lexical coding processes in
      verbal short-term memory and learning.

PMID- 8564476
TI  - Agrammatism in Spanish: a case study.
AB  - This article presents a case study of a Spanish-speaking Broca's patient with a
      selective deficit in syntactic production. The analysis indicates difficulties in
      processing certain abstract categories such as clitic pronouns without any other
      significant morphological errors. This pattern and the abundant use of strong
      pronouns in subject position are accounted as a syntactic production deficit
      related to the computation of phonetically null elements e that enter in a
      syntactic chain. At the same time, the patient shows a milder problem in the
      production of canonical word order at the sentence level, which is also explained
      in syntactic terms.

PMID- 8564477
TI  - Takayasu's disease--current status.

PMID- 8564478
TI  - Re-endothelialisation in autogenous vein grafts.
AB  - OBJECTIVES: To clarify the course of re-endothelialisation (Re-E) in an entire
      graft and to establish the effect of immersion media for the preservation of
      endothelial cells. METHODS: Autogenous femoral veins of dogs were immersed in
      heparinised saline solution (n = 18) or heparinized autogenous blood (n = 18).
      After immersion, the grafts were implanted into bilateral femoral artery, and
      were retrieved 1 day to 4-8 weeks after implantation. RESULTS: For the grafts
      immersed in the heparinised saline solution, the values for % area of endothelial
      cell coverage before implantation, and at 1 day, 1 week, and 4 weeks after
      implantation were 44.9%, 6.2%, 14.5%, and 81.3%, respectively. For the grafts
      immersed in heparinised autogenous blood, the values were 73.5%, 20.6%, 79.2% and
      95.5%, respectively. However, such relatively rapid speed of Re-E slowed down
      considerably after 1 week following implantation in this group. CONCLUSIONS: The
      use of heparinized autogenous blood is strongly recommended as a preparation
      media for autogenous vein grafts. Almost all of the endothelial cells fall away
      in the earlier period after implantation and regenerate multifocally and
      irregularly. Re-E is incomplete even at 8 weeks after surgery, and we suggest
      that the area of incomplete Re-E may develop into intimal hyperplasia.

PMID- 8564479
TI  - A prospective epidemiological survey of the natural history of chronic critical
      leg ischaemia. The I.C.A.I. Group (gruppo di studio dell'ischemia cronica critica
      degli arti inferiori).
AB  - OBJECTIVE: To draw a picture of the different practices adopted for the
      diagnosis, specific treatment and general care of critical leg ischaemia (CLI) in
      the light of the recommendations of the recent Consensus Document. DESIGN:
      Prospective observational study. SETTING: A representative sample of vascular and
      general surgery, angiology, general medicine departments of the Italian National
      Health Service. SUBJECTS: Patients with leg ischaemia considered as chronic and
      critical according to the definition and diagnostic criteria adopted in each
      centre. CHIEF OUTCOME MEASURES: Epidemiological profile of the standard
      population; prevalence of definition criteria and of diagnostic and therapeutic
      procedures; short and medium-term clinical outcome as well as of the general
      vascular morbidity and mortality. MAIN RESULTS: Over a 3 month period, 574
      patients were recruited in 69 centres mainly on the basis of clinical findings of
      CLI (rest pain and/or trophic lesions). They had an adequate diagnostic
      assessment of their vascular lesions and a high cardiovascular risk in terms of
      prior morbidity and presence of risk factors. Over half of the patients underwent
      revascularisation and three quarters were given pharmacological treatments. At
      the end of the observation period, 50 patients had died (8.7%), three had had a
      myocardial infarction (0.5%), six a stroke (1.0%), 70 a major amputation (12.2%)
      and 103 had persistent CLI (17.9%). CONCLUSIONS: This survey confirms the
      dramatic prognosis of patients with CLI and provides an appropriate background
      and setting to conduct experimental clinical studies in this field.

PMID- 8564480
TI  - Angioscopy for quality control of saphenous vein during bypass grafting.
AB  - OBJECTIVES: Although autogenous vein is the conduit of choice for infrainguinal
      bypass grafting, some 20-30% of vein grafts fail during the first year
      postoperatively. Many of these failed veins are now known to have pre-existing
      pathological changes. Angioscopy enables intraoperative endoluminal visualisation
      of veins and can reveal anomalies, some previously unsuspected, despite
      preoperative Duplex ultrasound mapping and normal external appearances. The aim
      of this study was to compare angioscopic findings with contemporary histological
      appearances and with subsequent graft outcome and ultimately, to identify those
      endoluminal features which might be predictive for failure. METHODS: Angioscopic
      vein inspection was carried out using Olympus 1.4 and 2.2mm angioscopes in
      patients undergoing femoropopliteal/distal bypass. Severe disease in the veins of
      five patients led to preferential use of polytetrafluoroethylene (PTFE) for above
      knee bypasses. The remaining 38 videotaped sequences were reviewed by two
      surgeons and scored using a scale of 0 to 3, based on frequency and distribution
      of angioscopically detected lesions. These included haemorrhagic mural plaques,
      flimsy intraluminal strands, webs/bands and mobile/adherent thrombus. Vein
      harvested at operation was assessed by a pathologist according to the level of
      pre-existing abnormality. RESULTS: There were significant associations between
      angioscopy/histology scores and graft survival (chi 2 = 22.00; df:3; p < 0.001;
      chi 2 = 22.43; df:3; p < 0.001 respectively). There was a significant correlation
      between angioscopy and histology scores (R8 = 0.725; p < 0.001). CONCLUSIONS:
      Angioscopy allows immediate identification of the at risk, poor quality vein
      graft at the time of surgery, without the delays inherent with histological
      preparation and assessment. Recognition of abnormalities at angioscopy may
      ultimately improve graft outcome by prospectively eliminating use of poor vein.

PMID- 8564481
TI  - Prevention of distal embolisation during abdominal aortic surgery.

PMID- 8564482
TI  - Inhibition of intimal hyperplasia in balloon injured arteries with adjunctive
      phthalocyanine sensitised photodynamic therapy.
AB  - OBJECTIVES: We investigated the effects of Photodynamic therapy (PDT) using
      Aluminium disulphonated phthalocyanine (AlS2Pc) on experimental intimal
      hyperplasia (FCIH). MATERIALS AND METHODS: (a) Pharmacokinetics: Normal rats were
      injected with Als2Pc and carotid artery fluorescence was measured. (b) Normal
      artery PDT: Sensitised rats underwent carotid artery laser irradiation (50J/cm2,
      675nm) and were assessed after 3 and 14 days and 1-6 months. (c) PDT: Rats
      underwent standard carotid artery balloon injury immediately prior to PDT and
      arteries were assessed at 2 to 26 weeks, together with laser, AlS2Pc, and
      untreated controls. CHIEF OUTCOME MEASURES: (a) Fluorescence intensity in
      different arterial layers. (b) Medial smooth muscle cell counts per high power
      field (light microscopic). (c) Percentage amount of FCIH (area of intimal
      hyperplasia) as a ratio of the IEL (area enclosed by the internal elastic
      lamina). RESULTS: (a) AlS2Pc fluorescence intensity increased with increasing
      dosage, with maximal fluorescence in the arterial media at 30 min. (b) PDT
      produced medial cell depletion at 3 days and persisted over 6 months without loss
      of vessel integrity. (c) PDT completely inhibited FCIH at 2 and 4 weeks. This was
      partial at 6 to 26 weeks (51% of untreated level). PDT inhibition of FCIH was
      significantly greater than in any of the control groups. p < 0.0001. Mann-Whitney
      Test. CONCLUSION: Adjunctive AlS2Pc sensitised photodynamic therapy inhibits
      experimental intimal hyperplasia, by causing medial smooth muscle cell depletion.
      This offers a new approach to the management of angioplasty restenosis in
      patients.

PMID- 8564483
TI  - Detection of sub-critical arterial stenoses by hyperaemic Doppler.
AB  - OBJECTIVES: This study assessed the potential of hyperaemic Doppler to detect sub
      critical stenoses using a flowrig model. METHODS: Pulsatile flow of a blood
      substitute was produced in a compliant circuit. A cadaver carotid artery,
      constricted by a silk suture produced a variable, focal stenosis. Forty-seven
      stenoses were created in five arteries. Pressure gradients and Doppler
      measurements were recorded simultaneously across each stenosis at low (200
      ml/min) and high (400 ml/min) flow rates. The change in peak velocities between
      the arterial segment 2cm proximal to the stenosis (V1), and the stenotic jet (V2)
      were used to calculate three Doppler indices: (i) V2/V1 ratio, (ii) V2-V1
      difference, (iii) a modified 'Bernoulli' value. A high flow pressure gradient of
      > or = 15% of the resting distal pressure (% delta P), represented a significant
      stenosis. RESULTS: There was improved correlation between Doppler indices and %
      delta P at high flow (r = 0.87 to 0.88) compared to low flow rates (r = 0.81 to
      0.84). Optimum V2/V1 cut off values were determined by received operator
      characteristics (ROC) curve analysis. At low flow five sub-critical stenoses were
      not detected (sensitivity 82.8%) yet all but one of these lesions were identified
      at high flow (sensitivity of 96.6%). The V2-V1 and Bernoulli indices did not
      improve on the discriminant ability of the V2/V1 ratio. CONCLUSIONS: The V2/V1
      ratio is sensitive to haemodynamic changes at enhanced flow rates across ideal
      arterial stenoses. The potential of hyperaemic Doppler to detect sub-critical
      lesions and so avoid intraarterial pressure measurements deserves further in vivo
      study.

PMID- 8564484
TI  - The degree of porosity influences the release of growth factors by healing
      polytetrafluoroethylene (PTFE) grafts.
AB  - OBJECTIVES: The aim of this study was to determine the influence of the degree of
      porosity on the release of growth factors (PDGF AA, PDGF BB, bFGF) by healing
      PTFE grafts. DESIGN AND SETTING: Laboratory animal study. MATERIALS: 1 cm long
      segments of non-reinforced PTFE grafts (30 microns fibril length, 2 mm internal
      diameter, 0.39 mm thick) were placed as an abdominal aortic interposition in
      Lewis rats. Fifteen grafts served as control (Group A; porous grafts); in eight
      rats (Group B; non porous grafts) the PTFE graft was completely wrapped by a non
      porous plastic envelope. Animals were killed 4 weeks after surgery. OUTCOME
      MEASURES: The release of PDGF AA, PDGF BB and bFGF was assessed by Enzyme Linked
      Immunosorbent Assay (ELISA). RESULTS: The release of PDGF AA, PDGF BB and bFGF
      was statistically higher in porous grafts. The only histological difference
      between the two groups was that porous PTFE grafts were invaded by many tufts of
      capillaries from the surrounding tissue, whereas this phenomenon was absent in
      non porous PTFE grafts. CONCLUSIONS: The degree of porosity influences the
      release of growth factors by healing PTFE grafts. This fact may have implication
      in the endothelisation of PTFE grafts and in myointimal hyperplasia formation as
      well.

PMID- 8564485
TI  - A comparison of quality control methods applied to carotid endarterectomy.
AB  - OBJECTIVES: To compare the ability of continuous wave Doppler (CWD), B-mode
      ultrasound (BMU), angioscopy and transcranial Doppler (TCD) to detect technical
      error during carotid endarterectomy (CEA). DESIGN: A prospective, comparative
      study in 100 consecutive patients. SETTING: Leicester Royal Infirmary, Leicester,
      U.K. MATERIALS: Intraoperative TCD monitoring was performed using a SciMed PcDop
      842 2 MHz TCD. An Olympus 2.8mm flexible angioscope was used to inspect the
      arterial lumen prior to restoration of bloodflow. After restoration of flow 10Mhz
      BMU images and 8Mhz CWD velocity spectra of carotid artery blood flow were
      obtained. CHIEF OUTCOME MEASURES: The detection of intimal flaps, thrombus,
      stenoses or other errors of surgical technique likely to result in perioperative
      morbidity. MAIN RESULTS: CWD and BMU images were technically inadequate in 9% and
      24% of cases respectively and neither technique altered clinical management.
      Angioscopy demonstrated significant technical errors in 12 cases (four intimal
      flaps, thrombus in eight). TCD detected shunt malfunction in 13% of patients,
      emboli during dissection in 23% and early postoperative carotid artery thrombosis
      in three patients. CONCLUSIONS: A combination of TCD monitoring and completion
      angioscopy provided the maximum yield in terms of diagnosing technical error and
      establishing the cause of perioperative morbidity.

PMID- 8564486
TI  - Prognosis in elderly men with screening-detected abdominal aortic aneurysm.
AB  - OBJECTIVES: To study the natural course of screening-detected symptomless
      abdominal aortic aneurysm (AAA) in elderly men. SETTING: Malmo, a city in
      southern Sweden with 230,000 inhabitants and a single referral hospital.
      MATERIALS: 423 seventy-four-year-old men, randomly selected from the population
      and belonging to the prospective population study "Men born in 1914", were
      invited. 343 underwent AAA screening, whereas 80 declined or had moved. CHIEF
      OUTCOME MEASURES: Five year all cause mortality in relation to participation in
      and findings at ultrasound screening for AAA. MAIN RESULTS: An abdominal aortic
      aneurysm was present in 38 (11%) out of 340 men who underwent screening and who
      had a native aorta. During 5 years of follow-up, one third (13/38) of these men
      died; 7 from myocardial infarction and 3 from stroke. The mortality rate in men
      with AAA was 80.2/1000 person years; twice as high as it was in men without AAA
      (39.4/1000 person years; p = 0.018). Six men underwent AAA surgery. None of them
      died from aneurysm rupture. However, aneurysm surgery did not reduce the total
      mortality rate in these men. The highest mortality rate, 91.9/1000 person years,
      was found in the men who did not participate in the screening. CONCLUSIONS: It is
      our conclusion that screening for early detection and intervention is of
      questionable value from a public health perspective.

PMID- 8564487
TI  - Human saphenous vein organ culture: a useful model of intimal hyperplasia?
AB  - OBJECTIVES: Although cell culture techniques and animal models of intimal
      hyperplasia have increased our current understanding of the aetiology of vein
      graft stenosis, the results of such studies have been difficult to relate to the
      human situation. DESIGN: The present study was designed to validate an organ
      culture of human saphenous vein by comparing the changes occurring in cultured
      vein with those seen in pathological vein graft stenoses and to identify a
      suitable marker of cell proliferation. MATERIALS AND METHODS: Saphenous vein
      segments were cultured for 14 days, fixed in formalin and processed for
      immunohistochemistry. Freshly excised stenoses were fixed and processed
      similarly. A number of markers of cell proliferation were evaluated in the
      culture system in order to identify the one best suited to this particular model.
      RESULTS: Marked similarities were observed in the cellular and extracellular
      matrix composition, and electron microscopy revealed that both the neointima of
      the cultured vein and the pathological lesion contained an abundance of smooth
      muscle cells of a secretory phenotype. Bromodeoxyuridine proved to be the most
      reliable proliferation marker and revealed that early proliferation in the
      superficial layers of the vein intima gave rise to the formation of neointima.
      Both proliferation and neointimal thickness were maximal by day 14 in culture.
      Proliferation declined rapidly thereafter, and the neointima was maintained.
      CONCLUSIONS: The changes occurring in cultured vein and graft stenoses bore many
      similarities, thereby justifying the use of organ culture as a valuable
      experimental tool.

PMID- 8564488
TI  - Low molecular mass heparin instead of unfractionated heparin during infrainguinal
      bypass surgery.
AB  - OBJECTIVES: To test whether low molecular mass heparin (LMMH) is comparable to
      unfractionated heparin (UFH) as an anticoagulant during infrainguinal bypass
      surgery and to investigate laboratory evidence of hypercoagulation in patients
      undergoing infrainguinal bypass surgery. MATERIALS AND METHODS: Eighteen patients
      were randomised to receive either UFH or LMMH (70 anti-Xa units/kg b.w.). Soluble
      fibrin, measured as fibrin monomers (FM) and fibrinopeptide A (FPA), were
      measured in blood from the femoral vein before, during and after release of the
      occluding clamps during surgery. In addition, fibrinogen prothrombin complex,
      thrombin-antithrombin complex, platelets and antithrombin were measured before
      surgery. Heparin levels (Anti Xa) were measured during surgery. RESULTS:
      Increased levels of fibrinogen, FPA, thrombin antithrombin complex and FM were
      recorded prior to surgery. During surgery no further increase was noted. The anti
      Xa levels were slightly higher in patients with LMMH than in patients receiving
      UFH. Levels of FM were significantly lower in patients receiving LMMH. No
      difference in FPA was noted. A positive correlation between fibrinogen and FPA
      and FM respectively was recorded. Four patients, two in each group, were
      reoperated for graft occlusion. One patient in the UFH group required reoperation
      because of bleeding. CONCLUSIONS: LMMH is comparable to UFH as an anticoagulant
      during infrainguinal bypass surgery. Variables reflecting hypercoagulability are
      elevated in this group of patients and are positively correlated to the
      fibrinogen level. High fibrinogen levels could thus be a risk for perioperative
      thrombosis.

PMID- 8564489
TI  - Quality of life in patients with intermittent claudication.
AB  - OBJECTIVE: As intermittent claudication (IC) infrequently progresses to limb loss
      many clinicians adopt a conservative approach to treatment. Recently percutaneous
      transluminal angioplasty (PTA) has been applied to patients with IC. If this were
      to become the first line treatment for IC it would have major implications in
      terms of hospital facilities as well as cost. A measure is required, therefore,
      to decide on rationing of limited financial resources. "Quality of life" may be
      more influential in determining demand on services since objective medical
      criteria cannot give an insight into the patients feelings of well being. DESIGN:
      We applied the Nottingham Health Profile, by post, to a group of claudicants and
      age/sex matched controls. 70% responded from both groups. Claudicants who had
      recently received intervention were excluded, as were controls complaining of any
      leg pains on walking. RESULTS: The results showed that claudicants have greater
      perceived problems in the areas of energy, pain, emotional reactions, sleep, and
      physical mobility compared to controls (p < 0.05; Mann-Whitney Test). This was
      reflected by a significantly greater positive response rate to problems with
      activities of daily living (0.05 > p > 0.02; Chi-square Test) in the claudicant
      group. CONCLUSION: Because of the cost and resource implications of introducing
      measures such as PTA to the treatment of vast numbers of patients with IC, we
      suggest that trials are needed to compare various treatments using quality of
      life measurements in addition to traditional efficacy/safety parameters.

PMID- 8564490
TI  - Growth rate of infrarenal aortic aneurysms.
AB  - OBJECTIVE: To delineate the natural history of infrarenal aortic aneurysms with
      respect to growth rate. METHODS: A referral based series of 233 patients with
      abdominal aortic aneurysm was serially assessed by abdominal ultrasound. RESULTS:
      The mean age was 71 years and the median follow up 26 months (range 6-146). The
      mean growth rate of the series was 3.2mm/year. Division of the initial size into
      those less than 41 mm (128 patients), between 41-60 mm (92 patients) and those
      above 60 mm (13 patients) in AP diameter showed mean growth rates per year were
      2.6 mm/year, 4.1 mm/year and 6.5 mm/year. Examination of the relationship between
      aneurysm size and subsequent growth rate over the whole study period revealed a
      rank correlation of 0.19 (p = 0.002). Aneurysms were also observed to expand at
      an erratic rate both in terms of time and size. CONCLUSIONS: When the initial
      decision is to observe the patient, serial ultrasound examinations facilitate
      later judgements on the balance of risks in relation to surgical treatment.

PMID- 8564491
TI  - Chronic critical leg ischaemia must include leg ulcers.
AB  - OBJECTIVES: In a previous series on conservative treatment in patients with leg
      ulcers and severe arterial occlusive disease (systolic digital blood pressure
      (SDBP) < 30 mmHg) a 70% risk of leg amputation and a negligeable potential for
      ulcerhealing was found. This series assess the efficacy of arterial
      reconstruction in such patients. DESIGN: Retrospective study of consecutive
      patients in a department of vascular surgery and of dermatology in cooperation
      with the wound healing center. MATERIAL AND METHODS: Thirty-nine patients with 42
      ulcerated legs underwent arterial revascularisation. 88% of the procedures were
      distal to the inguinal ligament. MAIN RESULTS: One patient died postoperatively
      (3%). Seven (18%) had wound complications, but none had graft infections. After 1
      year the cumulative secondary patency was 90%, ulcer healing 70% and the limb
      salvage 90%. Thus only four legs (10%) had been amputated. CONCLUSIONS: Arterial
      revascularisation for leg ulcers is indicated when conservative treatment fails.
      Legs with ulceration and SDBP < 30 mmHg should be included in the concept of
      chronic critical ischaemia.

PMID- 8564492
TI  - Unstable carotid plaques: preoperative identification and association with
      intraoperative embolisation detected by transcranial Doppler.
AB  - OBJECTIVES: To investigate whether unstable carotid plaque characteristics, as
      determined by preoperative colour Duplex ultrasonography (CDU) and postoperative
      histological examination, were associated with particulate embolisation, detected
      by transcranial Doppler (TCD), during the initial dissection of the carotid
      bifurcation during carotid endarterectomy(CEA). DESIGN: A prospective,
      consecutive study was undertaken of 50 patients undergoing carotid
      endarterectomy(CEA). SETTING: Leicester Royal Infirmary, Leicester, U.K.
      MATERIALS: Carotid plaques were assessed preoperatively using CDU. Intraoperative
      TCD monitoring of the ipsilateral middle cerebral artery was performed using a
      Scimed 2MHz TCD. Carotid plaques removed at operation were processed
      histologically and multiple sections assessed microscopically. CHIEF OUTCOME
      MEASURES: Plaque composition was classified ultrasonically and histologically
      according to the Gray-Weale classification and plaque surface characteristics
      were graded according to a five point classification. TCD detected emboli were
      identified and counted during the initial dissection of the artery. MAIN RESULTS:
      Particulate embolisation occurred in nine patients. Histologically, embolisation
      was associated with ulcerated plaque in three cases and ulcerated plaque with
      associated thrombus in six cases (p = 0.0005). However, the ability of CDU to
      positively predict embolisation based on the correct identification of an
      unstable plaque surface was only 25%. CONCLUSIONS: Embolisation during dissection
      is strongly associated with ulcerated plaque with associated thrombus. CDU is
      unable to reliably identify these characteristics preoperatively. Intraoperative
      TCD monitoring can detect potentially harmful embolisation during this stage
      enabling surgical technique to be modified appropriately.

PMID- 8564493
TI  - Use of transcranial Doppler sonography and acetazolamide test to demonstrate
      changes in cerebrovascular reserve capacity following carotid endarterectomy.
AB  - OBJECTIVES: To assess the effect of carotid endarterectomy on cerebrovascular
      reserve capacity. METHODS: Cerebral blood flow velocity (CBFV) and
      cerebrovascular reserve capacity (CVRC) were measured by transcranial Doppler
      sonography (TCD) and acetazolamide test in 40 patients who underwent
      uncomplicated unilateral carotid endarterectomy (CEA). Indication for operation
      was limited to stenoses > 70% as documented by angiography and/or Duplex
      scanning. The TCD studies were carried out 6 days (range 1-14 days) before and 8
      days (range 5-12 days) after endarterectomy. RESULTS: Before endarterectomy,
      resting CBFV values and CVRC in the 40 patients were significantly different
      between the operated (51 +/- 19 cm/s; 20 +/- 16%) and the non-operated (60 +/- 19
      cm/s; 34 +/- 24%) hemisphere (p < 0.05;p < 0.01). After CEA the overall increase
      of resting CBFV of the operated side was highly significant with preoperative
      CBFV values of 51 +/- 19cm/s and postoperative values of 62 +/- 15 cm/s (p <
      0.01). Cerebrovascular reserve capacity after operation was increased on both
      sides significantly (non-operated side: from 34 +/- 24% to 43 +/- 19%, p < 0.05;
      operated side: from 20 +/- 16% to 51 +/- 18%, p < 0.001), and the preoperative
      asymmetry was no longer present. CONCLUSIONS: CEA has a beneficial effect on the
      cerebral circulation in most patients, even those who presented with asymptomatic
      carotid artery stenosis. Since CVRC has been assessed in the early postoperative
      period, our findings also suggest that cerebral vascular adaption occurs within 2
      weeks after CEA.

PMID- 8564494
TI  - A new animal model for abdominal aortic aneurysms:initial results using a
      multiple-wire stent.
AB  - OBJECTIVES: The effect of a plain 48-wire self-expanding flexible stent
      (Wallstent-Schneider (Europe) AG) on abdominal aortic aneurysms has been studied
      in a new animal model. METHODS: Aneurysms were created by interposing fusiform
      segments of glutaraldehyde-tanned bovine internal jugular vein into the
      infrarenal aortas of 12 Large White pigs. The first six pigs were assessed after
      6 weeks by ultrasonography and arteriography; they were then sacrificed for
      pathological examination. Endovascular placement of the stents, 2 weeks after
      aneurysm creation, was performed under arteriographic control in the next six
      pigs. These pigs were assessed by ultrasonography and arteriography 6 weeks after
      stenting; they were then sacrificed for pathological examination. RESULTS: At 6
      weeks the aneurysms in the first group were pulsatile with partial
      endothelialisation and no mural thrombus. Placement of the stent in the second
      group was accomplished easily. Stenting resulted in an immediate reduction in
      wall pulsatility of all aneurysms and thrombosis of the excluded aneurysm sac
      occurred in three cases. In the other three cases the pulse pressure in the sac
      was reduced. In all cases there was a significant reduction in maximum aneurysm
      diameter when measured 6 weeks after stenting. CONCLUSIONS: A pulsatile, non
      thrombogenic aortic aneurysm model approaching human dimensions has been
      successfully developed for the study of endoprostheses prior to their clinical
      use. Endovascular placement of a plain, multiple-wire Wallstent was associated
      with reductions in aneurysm pulsatility, pulse pressure within the sac and
      maximum aneurysm diameter over the study period. Stenting was associated with
      thrombosis of the excluded aneurysm sac in 50% of cases.

PMID- 8564495
TI  - Avoiding infrainguinal bypass wound complications in patients with chronic renal
      insufficiency: the role of the anatomic plane.
AB  - OBJECTIVE: To study the factors leading to wound problems in patients with
      chronic renal insufficiency (CRI) with emphasis on subcutaneous vs. deep
      placement of grafts. METHODS: The outcomes of patients undergoing an
      infrainguinal bypass with preoperative CRI (serum creatinine > or = 2.0 mg/dl)
      were reviewed. Surgical site infection (SSI) was classified as superficial or
      deep according to the Centres for Disease Control standards. RESULTS: Forty-two
      patients underwent a total of 47 infrainguinal bypasses for ischaemic rest pain
      or tissue loss. The graft location was partially or predominantly subcutaneous in
      21 limbs (Group I) and 26 grafts were positioned in the anatomic or subfascial
      planes (Group II). In Group I, seven early (< 30 days postoperative), one
      intermediate (4-6 weeks postoperative), and one late (> 6 weeks postoperative)
      SSI's were found (9/21, 43%). In three of these patients the graft was exposed
      and two required removal. In contrast, only two early and one intermediate SSI's
      (3/26, 12%) were noted in Group II (p = 0.02). A logistic regression analysis,
      with twelve possible covariables wound healing, confirmed the subcutaneous
      location to be the only controllable factor significantly predicting SSI
      (relative risk = 11.6, p = 0.01). CONCLUSIONS: The infrainguinal bypass in
      patients with CRI is associated with a high incidence of wound complications. In
      our retrospective series, the presence of a vascular conduit in the subcutaneous
      plane was connected with a higher rate of SSI. Despite the growing trend toward
      the use of the in situ bypass, CRI may represent a circumstance where deeply
      placed grafts should be used preferentially.

PMID- 8564496
TI  - When less is more; when less is less.

PMID- 8564497
TI  - Nefazodone: a novel antidepressant.

PMID- 8564498
TI  - Employment settings of psychologists.

PMID- 8564499
TI  - "Carving in," and keeping in, mental health care in the managed care setting.

PMID- 8564500
TI  - Mental health benefit design: striving to achieve parity in Washington State.

PMID- 8564501
TI  - Effectiveness and cost of specific treatment elements in a program for homeless
      mentally ill veterans.
AB  - OBJECTIVES: The study examined relationships between specific treatment elements
      and their costs and ten outcome measures using data from a longitudinal outcome
      study of a Veterans Affairs program for homeless mentally ill veterans. METHODS:
      Baseline and outcome data over an eight-month period were analyzed for 406
      homeless veterans with psychiatric and substance use disorders who were treated
      in VA's Homeless Chronically Mentally Ill Veterans Program. Multivariate
      techniques were used to examine the relationship between ten measures of outcome
      and six treatment elements: program entry via community outreach, the number of
      contacts with program clinicians, the number of referrals for other services,
      duration of program involvement, number of days of residential treatment, and
      increased public support payments. RESULTS: Each of the six treatment elements
      was significantly related to improvement on at least one of the ten outcome
      measures. The number of clinical contacts with program staff and the number of
      days in residential treatment were associated with improvement in the greatest
      number of outcome domains. However, improvement associated with residential
      treatment was far more costly than improvement related to other treatment
      elements. CONCLUSION: This study provides evidence of the effectiveness of a
      multimodal approach to the treatment of homeless mentally ill persons. However,
      results indicate that special attention should be paid to to differences in the
      cost of improvement associated with various treatment elements.

PMID- 8564502
TI  - Mental health service use among homeless and never-homeless men with
      schizophrenia.
AB  - OBJECTIVE: The study compared patterns of previous mental health service use
      among 100 homeless men with schizophrenia and 100 men with schizophrenia who had
      never been homeless and explored whether differences in use of services were
      related to severity of illness. METHODS: Subjects were recruited from shelters,
      clinics, and inpatient psychiatric programs in New York City. Clinical
      interviewers used standardized research instruments to collect data on
      psychiatric treatment history, mental health service use within the past 12
      months, adequacy of discharge planning from the most recent psychiatric
      hospitalization, positive and negative-symptom levels, and presence of concurrent
      substance abuse and antisocial personality disorder. RESULTS AND CONCLUSIONS:
      Homeless subjects and never-homeless subjects had similar treatment histories and
      recent patterns of inpatient, outpatient, and emergency service use. However, the
      homeless men were more likely to have been discharged from their most recent
      psychiatric hospitalization against medical advice and to have less adequate
      discharge planning for living arrangements, aftercare, and finances. Inadequacies
      in discharge planning were most apparent among homeless men with triple disorders
      of schizophrenia, substance abuse, and antisocial personality disorder.

PMID- 8564503
TI  - Factors in the quality of patient evaluations in general hospital psychiatric
      emergency services.
AB  - OBJECTIVES: The study examined the usefulness of a three-perspective model for
      determining the quality of evaluations in psychiatric emergency services. The
      model was used to evaluate the hypothesis that the provision of high-quality care
      in emergency services is primarily influenced by service objectives related to
      patients' clinical characteristics rather than by institutional constraints, such
      as workload or physical facilities, or by social biases, such as clinicians'
      attitudes toward patients or perceptions of community expectations. METHODS: The
      evaluation of 683 persons assessed in nine California public facilities were
      independently observed. Multivariate techniques were used to test the relative
      importance of patients' clinical characteristics, possible sources of social bias
      among clinicians, and institutional constraints in influencing three quality-of
      care dimensions: technical quality, the art of patient care, and optimum
      investment of time. RESULTS: The findings generally confirmed the hypothesis that
      patients' clinical characteristics have more influence on the quality of care
      provided than institutional constraints or social biases. However, one
      institutional constraint--increased workload demands--led to reduced technical
      quality and to less than optimal use of time. Further, social biases reflected in
      the clinician's like for and preconceptions about the patient also influenced the
      quality of their evaluations. CONCLUSIONS: The model is a useful tool for
      examining quality of care in the psychiatric emergency service. Increasing
      workload pressures negatively affect quality of care.

PMID- 8564504
TI  - Effects of parental involvement on the functioning of noninstitutionalized adults
      with schizophrenia.
AB  - OBJECTIVES: The study described the nature and extent of parental families'
      involvement with adult children with schizophrenia who lived in noninstitutional
      settings in the community and examined the association between families'
      involvement and the adult children's clinical and psychosocial functioning.
      METHODS: A total of 193 subjects with schizophrenia were interviewed to obtain
      data on their contact with their families, clinical and psychosocial functioning,
      risk of victimization and substance use, and global functioning. RESULTS: Twenty
      three percent of the subjects lived with their parental families on some time
      during the previous six months. Nearly two-thirds of those who did not live with
      their families had contact with them an average of twice a week. Subjects who did
      not live with their families scored significantly higher on global functioning
      and on measures of contact with friends, dating, number of days worked,
      independence from family, and stability of living situation. Those who lived with
      their families were less likely to have been victimized or to have used
      substances. Among subjects who did not live with their families, those who
      maintained contact scored higher than those without contact on measures of days
      worked and overall role functioning. CONCLUSIONS: The nature of parental
      families' involvement with adult children with schizophrenia varied widely.
      Whether families' involvement was associated with higher levels of functioning
      varied with the subjects' living situation.

PMID- 8564505
TI  - Adaptive coping among family members of persons with serious mental illness.
AB  - OBJECTIVE: This study sought to describe factors associated with adaptive coping
      by family members with a psychiatrically disabled relative. METHODS: A total of
      225 family members of persons with serious mental illness were interviewed.
      Hierarchical regression analysis using five variables that may have contributed
      to adaptive coping was conducted. The five factors were demographic
      characteristics of the family member, severity of the relative's illness, the
      family member's subjective burden and grief, social support, and personal coping
      resources (self-efficacy and mastery). RESULTS: More extensive adaptive coping
      was associated with increased social support as measured by the density of the
      social network, the extent of affirming social support, and participation in a
      support group for families. Better coping was also associated with a greater
      sense of self-efficacy in dealing with the relative's mental illness. Adaptive
      coping was not associated with the severity of the relative's illness.
      CONCLUSIONS: The findings suggest that mental health professionals should
      encourage family members to use the support provided by community-based support
      groups and to form such groups if none are available.

PMID- 8564506
TI  - Quality of life and clinical predictors of rehospitalization of persons with
      severe mental illness.
AB  - OBJECTIVE: The study examined whether rehospitalization of patients with severe
      and persistent mental illness could be predicted by patients' quality of life.
      The predictive ability of two clinical factors associated with rehospitalization-
      history of hospitalizations and severity of symptoms--was also examined. METHODS:
      A total of 559 patients were assessed at two follow-up points, two and 12 months
      after an index hospital discharge. Patients who were rehospitalized and those who
      were not rehospitalized between the two follow-up points were compared on
      subjective and objective quality of life, symptom severity at first follow-up,
      and previous rehospitalization. Multivariate analysis was used to determine the
      best predictors of rehospitalization. RESULTS: Compared with patients who were
      not rehospitalized, those who were rehospitalized had more severe symptoms and
      were more likely to have a history of hospitalization. Rehospitalized patients
      reported more dissatisfaction with family relations and were more likely to
      report an arrest in the past two months. The two groups did not differ in other
      quality-of-life domains and in global quality of life. CONCLUSIONS: The best
      predictors of rehospitalization were previous rehospitalization, more severe
      symptoms, and dissatisfaction with family relations. Interventions should promote
      positive relationships between patients with severe mental illness and their
      families to reduce the risk of relapse and rehospitalization.

PMID- 8564507
TI  - Who cares? Pathways to psychiatric care for young people experiencing a first
      episode of psychosis.
AB  - OBJECTIVE: The authors reviewed the literature to better understand pathways to
      psychiatric care among young persons experiencing a first episode of psychosis.
      Because no discrete body of literature exists about how young people with
      psychotic illness gain access to psychiatric services, the authors examined three
      related areas: illness recognition, help-seeking, and referral pathways. METHODS:
      Automated and manual searches of primarily medical and psychological sources from
      1977 to 1995 were conducted. RESULTS: The review found evidence of delay in
      obtaining early treatment among young people with an emerging psychosis, although
      comparisons between studies are difficult. Early psychiatric intervention is
      believed to significantly aid recovery and is an increasingly important clinical
      issue. Recognizing psychiatric illness is problematic for professionals and
      nonprofessionals. CONCLUSIONS: Understanding of help seeking by patients
      experiencing a first psychotic episode and of their referral pathways is limited.
      Taken together, studies suggest factors affecting access to treatment but provide
      neither sufficient empirical information nor an adequate conceptual framework to
      better target secondary prevention strategies. Formulation of a pathways-to-care
      model appears to offer a useful way of understanding mental health care use.
      Exploration of consumer experiences would enrich the model. Strategies to reduce
      treatment delay could then be developed and evaluated. Increased consumer
      involvement might help ensure that services are better tailored to patients'
      needs.

PMID- 8564508
TI  - Refocusing the training of psychiatric rehabilitation staff.
AB  - The authors describe an approach to training staff in psychiatric rehabilitation
      programs that is based on principles of organizational psychology. The approach
      promotes two shifts in the focus of training. First, training efforts should not
      only educate individual staff members about state-of-the-art rehabilitation
      skills but also organize the treatment team into a system that will consistently
      carry out these skills. Second, training should help the team develop user
      friendly programs rather than insisting on faithful implementation of state-of
      the-art interventions. A four-phase, eight-step training method called
      interactive staff training that can help programs achieve these goals is
      presented. The first phase involves obtaining administrative support for change,
      assessing staff needs, and forming a program committee. In the second phase,
      staff participate in decision making about program components, and a facilitator
      conducts sessions to reach consensus on a draft program. A pilot program is
      implemented and evaluated in the third phase. In the final phase, a user-friendly
      program is maintained through continuous quality improvement.

PMID- 8564510
TI  - Functional capabilities of depressed patients one year after hospitalization.
AB  - During hospitalization and at one-year follow-up, 48 patients with a diagnosis of
      major depression completed the Inventory to Diagnose Depression and the Sickness
      Impact Profile (SIP). Overall change scores revealed statistically significant
      and clinically important improvements in depression and functioning. SIP subscale
      scores showed no deficits in some functions (communication and bodily care) at
      baseline, restoration of functioning in other activities at one-year follow-up,
      and continuing dysfunctions in emotionality, alertness, recreation,
      socialization, and work. The SIP appears useful for measuring disability and
      patterns of recovery in depressed patients.

PMID- 8564509
TI  - Effects of Medicare's prospective payment system on service use by depressed
      elderly inpatients.
AB  - OBJECTIVE: To determine the effects of Medicare's prospective payment system
      (PPS) on hospital care, changes in length of stay and intensity of clinical
      services received by 2,746 depressed elderly patients in 297 acute care general
      medical hospitals were studied. METHODS: A pre-post design was used, and
      differences in sickness at admission were controlled for. Data on length of stay
      and use of specific clinical services were obtained from the medical record using
      a medical record abstraction form. Care provided on units exempt from PPS was
      compared with care provided in nonexempt units. RESULTS: After implementation of
      PPS, the average length of stay fell by up to three days within the different
      types of acute care settings studied, but this decline was partially offset by
      proportionately more admissions to psychiatric units, which had longer lengths of
      stay. Intensity of clinical services increased after PPS implementation,
      especially in nonexempt psychiatric units. CONCLUSION: Despite financial
      incentives for hospitals to reduce clinical services under PPS, its
      implementation was not associated with a marked decline in length of stay, when
      averaged across all treatment settings, and was associated with an increase in
      the intensity of many clinical services used by depressed elderly patients in
      general hospitals.

PMID- 8564511
TI  - Preliminary results from a psychoeducational program to rehabilitate chronic
      patients.
AB  - Twenty-two chronic psychiatric patients enrolled in a psychoeducational
      rehabilitation program were assessed before and after the program to determine
      whether participation decreased severity of psychopathology and improved
      community functioning and quality of life. The program consisted of five 14-week
      modules that provided training in five skill areas: medication and symptom self
      management, coping with anxiety and depression, social skills, living skills, and
      leisure skills. Most patients experienced significantly reduced psychopathology
      and negative symptoms and improved quality of life and community functioning. The
      program appears helpful to clients, and a controlled trial to further evaluate
      its effects is underway.

PMID- 8564512
TI  - Informational needs of patients hospitalized for bipolar disorder.
AB  - Thirty-three inpatients (20 women and 13 men) with bipolar disorder participated
      in audiotaped, semi-structured interviews that focused on their informational
      needs in six areas: self-management of the disorder, understanding bipolar
      disorder, managing daily life, living in society, relating to others, and
      relating to self. The interviews were transcribed and systematically analyzed to
      produce a typology of needs, which was evaluated by the interviewees as it
      evolved. The typology is useful for structuring psychoeducational programs. The
      findings attest to the importance of providing education for persons with bipolar
      disorder in all health care settings in which they seek treatment.

PMID- 8564513
TI  - What's a psychiatrist to do?

PMID- 8564514
TI  - National survey finds increases in illicit drug use by 12- to 17-year-olds and
      adults over 35.

PMID- 8564516
TI  - Actions of PAF receptor antagonists in horses with the allergic skin disease
      sweet itch.
AB  - Platelet activating factor (PAF) mimics the effects of Culicoides antigen by
      inducing oedema and inflammatory cell accumulation in the dermis of horses with
      the allergic skin disease, sweet itch. PAF could therefore contribute to antigen
      induced inflammatory changes in these horses. We now report that intravenous
      administration of the PAF receptor antagonist WEB 2086 (3 mg kg-1), at a dose
      that inhibited the vascular and cellular responses to PAF in sweet itch horses,
      reduced Culicoides antigen-induced oedema at 1 h by 73% and at 8 h by 71% (p <
      0.05). Neutrophil accumulation and eosinophil recruitment were not significantly
      reduced by WEB 2086 or a second hetrazepine PAF receptor antagonist WEB 2170 (0.1
      mg kg-1). These findings suggest a key role for PAF in oedema formation, but not
      inflammatory cell accumulation, induced by Culicoides antigen in the skin of
      sweet itch horses.

PMID- 8564515
TI  - Pain due to nerve damage: are inflammatory mediators involved?
AB  - Damage to peripheral nerves often results in pain and hyperalgesia. We suggest
      that nerve damage causes an inflammatory response in which cells associated with
      the nerve release inflammatory mediators such as eicosanoids; these mediators may
      contribute to the hyperalgesia which results from nerve injury. The cell types
      most likely to be responsible include macrophages and postganglionic sympathetic
      neurones. A better understanding of the mechanisms involved should lead to
      improved therapies for neuropathic pain.

PMID- 8564517
TI  - Inhibition of nitric oxide synthase reduces Sephadex-induced oedema formation in
      the rat lung: dependence on intact adrenal function.
AB  - In the present study we have investigated the effect of L-nitro arginine mono
      methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase on Sephadex
      induced inflammation in the rat lung. Instillation of Sephadex into the airways
      induced an inflammatory reaction characterized by a long-lasting interstitial
      oedema, measured as an increase in lung weight, and an influx of inflammatory
      cells into the airways. L-NAME given s.c. prevented the increase in lung weight
      following Sephadex instillation. The inactive enantiomer D-NAME had no effect,
      nor did aminoguanidine which indicates that this effect of L-NAME was mediated by
      inhibition of the constitutive form of NOS. Treatment with L-NAME did not reduce
      an established oedema. In contrast, L-NAME tended to enhance the influx of
      oesinophils into the airways of Sephadex-instilled animals. L-NAME did not have
      any effect on the development of oedema in adrenalectomized rats or in animals
      where formation of glucocorticosteroids (GCS) was inhibited with metyrapone. L
      NAME did not however, increase plasma levels of corticosterone. The present
      results indicate that, in this model, inhibition of NO-synthesis has marked anti
      inflammatory effects. The underlying mechanism is complex but seems not to
      involve prevention of overproduction of NO.

PMID- 8564518
TI  - Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a
      new non-steroidal anti-inflammatory agent with favourable gastrointestinal
      tolerance.
AB  - The anti-inflammatory, analgesic and antipyretic properties of the new non
      steroidal anti-inflammatory agent, meloxicam, were investigated in a variety of
      animal models and compared with the properties of piroxicam, diclofenac,
      indomethacin and several other NSAIDs. With respect to the total effect of a
      single oral dose, the anti-exudative effect of meloxicam on carrageenan-induced
      oedema in the rat exceeded that of all the NSAIDs included in the comparison.
      Additionally, meloxicam showed the greatest potency of all the compounds examined
      with respect to adjuvant-induced arthritis in the rat, the granuloma pouch model
      and the cotton pellet test in the rat. Unlike indomethacin, in the carrageenan
      pleurisy model in the rat, meloxicam caused both a dose-dependent reduction in
      exudate volume and also inhibition of leucocyte migration. Meloxicam showed a
      strong and lasting effect on inflammatory pain in the rat. Like other NSAIDs, but
      unlike dipyrone, meloxicam had no effect in the hot plate and tail clamp tests,
      which are used to identify weak central analgesic effects. Unlike dipyrone and
      like indomethacin, meloxicam had no effect in a model of visceral distention
      pain. In common with other NSAIDs, meloxicam had no influence on the body
      temperature of normothermic rats in the anti-inflammatory dose range, but did
      reduce yeast-induced fever in the rat in a dose-dependent manner. Like piroxicam,
      meloxicam had a uricosuric effect on rats treated with oxonic acid. Low-dose
      meloxicam inhibited both bradykinin-induced and PAF-induced bronchospasm in the
      guinea-pig, but had no effect on acetylcholine-induced bronchospasm. Piroxicam
      had greater ulcerogenic effects in the rat stomach than meloxicam. The
      therapeutic range of meloxicam in the rat, with regard to inhibition of adjuvant
      arthritis, was several times greater than that of piroxicam, indomethacin,
      diclofenac and naproxen.

PMID- 8564519
TI  - Zonal differences in nitric oxide synthesis by bovine chondrocytes exposed to
      interleukin-1.
AB  - To determine the role of nitric oxide (NO) in the inhibition of aggrecan
      synthesis, we measured levels of NO produced by bovine chondrocytes from
      different layers of articular cartilage in the presence of interleukin-1 (IL-1).
      Chondrocytes from the superficial layer showed a large increase in NO synthesis
      in response to IL-1. Although chondrocytes from the deep layer also produced NO
      in response to IL-1, the amount was less than that from the superficial layer.
      Enhanced NO production evoked by IL-1 was accompanied by a significant inhibition
      of aggrecan synthesis. These data suggest that chondrocytes in both superficial
      and deep layer of articular cartilage inhibit aggrecan synthesis with IL-1 via NO
      production. In addition, superficial layer cells respond to lower amounts of IL-1
      with respect to NO-production and inhibition of proteoglycan synthesis.

PMID- 8564520
TI  - Serum protects against azurophil granule dependent down-regulation of complement
      receptor type 1 (CR1) on human neutrophils.
AB  - We have investigated the effect of gradual degranulation on the expression of
      functional receptors (CR1 and CR3) on human neutrophils. Incubation with
      increasing concentrations of fMLP (10(-10) - 10(-7) M) translocated CR1 and CR3
      to the cell surface in a similar kinetic pattern. When reaching maximal
      expression of receptors (10(-7) M fMLP), 78 +/- 10% and 87 +/- 9% of the total
      pool of CR1 and CR3, respectively, were translocated to the cell surface. To
      drive the mobilization process further, cytochalasin B was introduced to increase
      the stimulatory effect of fMLP. No further increase in CR1 surface expression was
      obtained. However, we found a characteristic time course of surface appearance of
      CR1 and CR3 with a maximal surface expression within 1 minute, followed by a time
      related down-regulation of CR1 but not CR3. In addition, the total pool of CR1 in
      cytochalasin B treated neutrophils was reduced after 15 minutes stimulation with
      fMLP measured by flow cytometry and immunoblotting, indicating degradation of
      CR1. The down-regulation of CR1 was concomitant with a translocation of azurophil
      granules, in terms of upregulation of CD63. Azurophil, but not specific nor
      secretory, granule fractions caused a down-regulation of CR1 on fMLP activated
      neutrophils. The presence of human sera and serine protease inhibitor protected
      CR1 from down-regulation. Together, these findings indicate that intracellular
      stored proteases, released in the late part of the sequential mobilization
      process, alters the expression of functional receptors mobilized in the early
      part of the mobilization process. The findings also focus on the importance of
      the microenvironment for the net outcome of neutrophil activation in terms of
      functional receptor expression.

PMID- 8564521
TI  - The source and action of histamine in the isolated guinea-pig gallbladder.
AB  - We have investigated the effects of histamine on motility of the gallbladder and
      characterized the receptor types involved. Histamine and the histamine H1
      receptor agonist, 2-thiazolylethylamine (2-TEA) contracted the isolated guinea
      pig gallbladder strip in a dose dependent manner. The contractile response to
      histamine was shifted to the right by the H1-receptor antagonist, mepyramine. In
      pre-contracted gallbladder strips, the H2-receptor agonist dimaprit reduced the
      tension generated in a dose dependent fashion. The histamine H2-receptor
      antagonist, ranitidine shifted the histamine concentration effect curve to the
      left and attenuated the dose dependent relaxations elicited at high
      concentrations. The histamine H3-receptor agonist, (R)-alpha-methylhistamine
      (RMHA) elicited dose dependent contraction of the tissue which was significantly
      inhibited in the presence of mepyramine. The effects of electrical field
      stimulation (EFS) on the strips were not significantly altered by the presence of
      RMHA (10(-10) - 10(-7) M) indicating little pre-synaptic H3 activity in this
      tissue. Histamine immunoreactivity (IR) was detected in gallbladder whole mount
      preparations of the mucosa and the muscularis/serosa. The histamine IR appeared
      cell bound in cells of varying morphological characteristics but no IR was
      detected in nerve fibres or cell bodies (ganglia). Alcian blue staining was
      consistent with the distribution of histamine IR cells as mast cells. The results
      indicate that histamine is distributed in the guinea-pig gallbladder and it can
      regulate contractile activity via activation of H1 and H2 but not H3 receptors.

PMID- 8564522
TI  - The effects of antiinflammatory and antiallergic drugs on cytokine release after
      stimulation of human whole blood by lipopolysaccharide and zymosan A.
AB  - IL-1 beta, IL-8, IL-6 and TNF alpha, derived from infiltrating leukocytes, are
      important mediators of inflammation in arthritic and allergic diseases.
      Heparinized human whole blood was evaluated as a model to study the effects of
      various classes of antiinflammatory drugs on cytokine release/biosynthesis from
      leukocytes. Whole blood was stimulated with zymosan A (1.5 mg/ml) or LPS (5
      micrograms/ml) for 4 h to induce cytokine release. Dexamethasone was the most
      potent inhibitor of TNF alpha, IL-1 beta, IL-6 and IL-8 release from LPS
      stimulated blood leukocytes (IC50s of 0.19, 0.11 microM, 0.16 and 0.07
      respectively). In LPS stimulated blood, SKF-86002, a 5
      lipoxygenase/cytooxygenasae inhibitor, and rolipram, a PDE IV inhibitor, also
      inhibited the release of TNF alpha (IC50s of 33 and 11 microM, respectively), IL
      1 beta (IC50s of 11 and 30 microM, respectively), IL-6 (IC50s of 56 and > 30,
      respectively) and IL-8 (IC50s of 6.7 and 15, respectively), whereas isoproterenol
      (1 microM) inhibited significantly only TNF alpha release. Nonsteroidal
      antiinflammatory drugs, 5-lipoxygenase inhibitors and immuno-suppressive drugs
      were inactive at 30 microM against LPS and zymosan A stimulation of cytokine
      release. Using zymosan A as the stimulus, only SKF-86002 (30 microM) showed
      significant inhibition of IL-1 beta (-59%). This 4 h human blood assay has the
      potential to identify novel inhibitors and sites of actions (e.g. transcription,
      post-transcriptional and secretion) of new antiinflammatory drugs.

PMID- 8564523
TI  - Modulation of the endothelial procoagulant response to lipopolysaccharide and
      tumour necrosis factor-alpha in-vitro: the effects of dexamethasone,
      pentoxifylline, iloprost and a polyclonal anti-human IL-1 alpha antibody.
AB  - Endothelial expression of tissue factor (TF), a potent procoagulant molecule, is
      increased in response to inflammatory mediators such as lipopolysaccharide (LPS),
      tumour necrosis factor (TNF) and interleukin-1 (IL-1). We have examined the
      effects of three antiinflammatory agents and a polyclonal anti-human IL-1 alpha
      antibody on the human endothelial TF response to E. coli 0111:B4 LPS and
      recombinant TNF alpha (rTNF alpha) in vitro. In contrast to the expected
      inhibitory effect, dexamethasone, pentoxyfilline and iloprost failed to block TF
      expression when administered simultaneously or 30 minutes prior to stimulation
      with either LPS or rTNF alpha. Inhibition of procoagulant activity was
      demonstrated with the anti-IL-1 alpha antibody, suggesting that endothelial
      derived IL-1 alpha is partially responsible for the TF response to the agonists
      employed. The failure of the antiinflammatory agents to inhibit endothelial TF
      expression highlights the possibility that therapeutic agents that modulate the
      circulating monocyte response to LPS and TNF alpha may not ameliorate the
      endothelial dysfunction that is also induced by these inflammatory mediators.

PMID- 8564524
TI  - Inhibitory effects of pentoxifylline on LPS-induced leukocyte adhesion and
      macromolecular extravasation in the microcirculation.
AB  - Pentoxifylline (PTX) has been shown to combat effectively endotoxin induced
      symptoms of shock or inflammation by reducing both leukocyte activation and
      endogenous cytokine formation. With regard to blood perfusion, inflammation is
      defined as a local reaction to injury of the living microvasculature and its
      content. Leukocyte margination, rolling, adhesion, and emigration is mediated by
      adhesion molecules along the endothelium of postcapillary venules and is
      considered to be an important step in the inflammatory response. Changes in the
      vascular integrity can be estimated in terms of increased extravasation of
      macromolecules. Using intravital microscopy with the help of an analogous video
      image processing system we measured the effect of PTX on lipopolysaccharide (LPS,
      15 mg/kg i.v.) induced leukocyte adhesion and extravasation of FITC-rat serum
      albumin (FITC-RSA) in rat mesenteric venules. The changes in vascular
      permeability correlates significantly (r = 0.75) with a locally increased number
      of adherent leukocytes. PTX significantly inhibits both leukocyte adhesion and
      extravasation of FITC-RSA dose dependently. Our results indicate that PTX
      effectively preserves vascular integrity in the microcirculation by acting
      primarily on LPS-induced leukocyte adhesion.

PMID- 8564526
TI  - Release of sulfidoleukotrienes in vitro: its relevance in the diagnosis of
      pseudoallergy to acetylsalicylic acid.
AB  - Pseudo-allergic reactions (PAR) are caused by a variety of drugs, of particular
      interest by acetylsalicylic acid (ASA) and other nonsteroidal antiinflammatory
      drugs. The clinical symptoms often resemble immediate type hypersensitivity
      reactions and consist of bronchospasm, urticaria, angioedema and even
      anaphylactic shock. Antigen specific immune mechanisms, however, are not
      involved. In general, skin tests are not reliable and the diagnosis of PAR is
      based mainly on risky provocation tests. Therefore, the purpose of this study was
      to establish procedures for in vitro diagnosis of PAR to ASA. A controlled study
      was performed including patients with PAR to ASA based on history and positive
      oral provocation test and non-atopic as well as atopic controls. In this in vitro
      study the production of sulfidoleukotrienes (sLT) by isolated leukocytes was
      measured by cellular allergen stimulation test (CAST), which is based on
      detection of LTC4, LTD4 and LTE4 by a monoclonal antibody. Accordingly, the
      direct effect of ASA as well as the modulatory effect of ASA on C5a-induced
      production of sLT in leukocytes in vitro was investigated. In patients with PAR
      to ASA, C5a-induced generation of sLT was significantly increased as compared to
      normal controls. In contrast, there was no difference in the spontaneous release
      of sLT in vitro in patients and controls. Preincubation of leukocytes with ASA
      did not exert a significant modulatory effect on the spontaneous or the C5a
      induced production of sLT in patients and controls. In summary, the present study
      provides a novel in vitro test system for the diagnosis of PAR to ASA by
      measurement of sLT release in leukocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8564525
TI  - Chlorpromazine inhibits nitric oxide-mediated increase in intracellular cGMP in a
      mouse teratocarcinoma cell line.
AB  - Chlorpromazine is a phenothiazine with a structure similar to that of methylene
      blue. Since methylene blue is a well known inhibitor of nitric oxide-induced
      cyclic GMP accumulation, we investigated whether chlorpromazine had the same
      effect. Cyclic GMP accumulation, induced in a mouse teratocarcinoma cell line
      (P19) by sodium nitroprusside (a nitric oxide releasing agent), was inhibited by
      both methylene blue (IC50 0.34 microM) and chlorpromazine (IC50 35 microM).
      Chlorpromazine's action was probably directed specifically at soluble guanylate
      cyclase, since the drug had no effect on ADP-ribosylation in rat hippocampus,
      another nitric oxide-affected, but cGMP-independent event.

PMID- 8564527
TI  - Effects of iodoproxyfan, a potent and selective histamine H3 receptor antagonist,
      on alpha 2 and 5-HT3 receptors.
AB  - We determined the affinity and/or potency of the novel H3 receptor antagonist
      iodoproxyfan at alpha 2 and 5-HT3 receptors. Iodoproxyfan and rauwolscine (a
      reference alpha 2 ligand) (i) monophasically displaced 3H-rauwolscine binding to
      rat brain cortex membranes (pKi 6.79 and 8.59); (ii) facilitated the electrically
      evoked tritium overflow from superfused mouse brain cortex slices preincubated
      with 3H-noradrenaline (pEC50 6.46 and 7.91) and (iii) produced rightward shifts
      of the concentration-response curve (CRC) of (unlabelled) noradrenaline for its
      inhibitory effect on the evoked overflow (pA2 6.65 and 7.88). In the guinea-pig
      ileum, iodoproxyfan 6.3 mumol/l failed to evoke a contraction by itself but
      depressed the maximum of the CRC of 5-hydroxytryptamine (pD'2 5.24). Tropisetron
      (a reference 5-HT3 antagonist) produced rightward shifts of the CRC of 5
      hydroxytryptamine (pA2 7.84). In conclusion, the affinity/potency of iodoproxyfan
      at H3 receptors (range 8.3-9.7 [1]) exceeds that at alpha 2 receptors by at least
      1.5 log units and that at 5-HT3 receptors by at least 3 log units.

PMID- 8564528
TI  - Endotoxin induced production of interleukin-6 is enhanced by vitamin E deficiency
      and reduced by black tea extract.
AB  - Studies were performed to investigate the effect of a polyphenol rich extract
      from black tea and vitamin E on bacterial lipopolysaccharide (endotoxin) induced
      IL-6 production, alterations in liver glutathione and antioxidant acute phase
      protein (caeruloplasmin) concentration, in rats fed on a synthetic diet for 21
      days. In the vitamin E sufficient group a significantly lower IL-6 concentration
      than in vitamin E deficient animals was observed. Addition of tea extract to the
      diet produced a similar reduction in IL-6, but no synergism occurred in the
      presence of both vitamin E and tea extract. However, a significantly lower
      caeruloplasmin and a significantly higher liver glutathione concentration was
      observed in rats fed both substances. It is suggested that consideration of
      dietary components which alter antioxidant/oxidant status may contribute towards
      treatment of inflammatory/autoimmune diseases.

PMID- 8564529
TI  - Release of cytokines from isolated lung strips by bradykinin.
AB  - Bradykinin as an inflammatory mediator was assayed for its ability to release
      cytokines from isolated lung tissue derived from guinea pigs, mice and in some
      cases from patients. Bradykinin elicited in concentrations, which were able to
      induce a contraction of isolated lung strips, a secretion of different cytokines
      from the tissue into organ baths as well as from lung tissue incubated in petri
      dishes (4h, 37 degrees C). Using enzyme immuno assays and the tanned erythrocyte
      electrophoretic mobility (TEEM)-test in combination with monoclonal antibodies
      the cytokines could be identified preferably as interleukin(IL)-1, IL-2, sIL-2R
      and IL-6. Tyrode solution as a control and carbachol in a concentration causing
      also a contraction were not able to release cytokines in a significant amount.
      The bradykinin B2 receptor antagonist icatebant (HOE 140) inhibited the
      bradykinin-induced IL-2 and IL-6 release. The results show that bradykinin can
      elicit the secretion of the cytokine cascade via a receptor-mediated process.

PMID- 8564530
TI  - Information please.

PMID- 8564531
TI  - Illuminating the ancient retainer.

PMID- 8564532
TI  - Protein gates in DNA topoisomerase II.

PMID- 8564533
TI  - Nuclear receptors spring into action.

PMID- 8564534
TI  - GroE structures galore.

PMID- 8564535
TI  - Picture story. Probing the pore.

PMID- 8564536
TI  - The N-terminal domain of TFIIB from Pyrococcus furiosus forms a zinc ribbon.
AB  - The three-dimensional structure of the N-terminal domain of an archaeal TFIIB,
      which has high sequence homology with eucaryal analogues, is strikingly similar
      to that of the C-terminal zinc ribbon of the eucaryal transcription elongation
      factor TFIIB.

PMID- 8564537
TI  - Neutron diffraction reveals the orientation of the headgroup of inositol lipids
      in model membranes.
AB  - Neutron diffraction studies show that the inositol ring in the headgroup of
      phosphatidylinositol extends perpendicular to the membrane surface but that
      phosphorylation of the 4-position causes the ring to tilt over.

PMID- 8564538
TI  - Biotin carboxylase comes into the fold.
AB  - Extensive three-dimensional structural resemblances between biotin carboxylase
      and the ADP-forming peptide synthetases, represented by glutathione synthetase
      and D-Ala:D-Ala ligase, reveal a previously unsuspected evolutionary relationship
      between two major families of ADP-forming ligases.

PMID- 8564539
TI  - Chitinases, chitosanases, and lysozymes can be divided into procaryotic and
      eucaryotic families sharing a conserved core.
AB  - Barley chitinase, bacterial chitosanase, and lysozymes from goose (GEWL), phage
      (T4L) and hen (HEWL) all hydrolyse related polysaccharides. The proteins share no
      significant amino-acid similarities, but have a structurally invariant core
      consisting of two helices and a three-stranded beta-sheet which form the
      substrate-binding and catalytic cleft. These enzymes represent a superfamily of
      hydrolases which are likely to have arisen by divergent evolution. Based on
      structural criteria, we divide the hydrolase superfamily into a bacterial family
      (chitosanase and T4L) and a eucaryotic family represented by chitinase and GEWL.
      Both families contain the core but have differing N- and C-terminal domains.
      Inclusion of chitinase and chitosanase in the superfamily suggests the archetypal
      catalytic mechanism of the group is an inverting mechanism. The retaining
      mechanism of HEWL is unusual.

PMID- 8564540
TI  - Exploring the allowed sequence space of a membrane protein.
AB  - We present a comprehensive view of the tolerance of a membrane protein to
      sequence substitution. We find that the protein, diacylglycerol kinase from
      Escherichia coli, is extremely tolerant to sequence changes with three-quarters
      of the residues tolerating non-conservative changes. The conserved residues are
      distributed with approximately the same frequency in the soluble and
      transmembrane portions of the protein, but the most critical active-site residues
      appear to residue in the second cytoplasmic domain. It is remarkable that a
      unique structure of the membrane embedded portion of the protein can be encoded
      by a sequence that is so tolerant to substitution.

PMID- 8564541
TI  - Crystallographic observation of a covalent catalytic intermediate in a beta
      glycosidase.
AB  - The three-dimensional structure of a catalytically competent glycosyl-enzyme
      intermediate of a retaining beta-1,4-glycanase has been determined at a
      resolution of 1.8 A by X-ray diffraction. A fluorinated slow substrate forms an
      alpha-D-glycopyranosyl linkage to one of the two invariant carboxylates, Glu 233,
      as supported in solution by 19F-NMR studies. The resulting ester linkage is
      coplanar with the cyclic oxygen of the proximal saccharide and is inferred to
      form a strong hydrogen bond with the 2-hydroxyl of that saccharide unit in
      natural substrates. The active-site architecture of this covalent intermediate
      gives insights into both the classical double-displacement catalytic mechanism
      and the basis for the enzyme's specificity.

PMID- 8564542
TI  - X-ray structure of an anti-fungal chitosanase from streptomyces N174.
AB  - We report the 2.4 A X-ray crystal structure of a protein with chitosan endo
      hydrolase activity isolated from Streptomyces N174. The structure was solved
      using phases acquired by SIRAS from a two-site methyl mercury derivative combined
      with solvent flattening and non-crystallographic two-fold symmetry averaging, and
      refined to an R-factor of 18.5%. The mostly alpha-helical fold reveals a
      structural core shared with several classes of lysozyme and barley endochitinase,
      in spite of a lack of shared sequence. Based on this structural similarity we
      postulate a putative active site, mechanism of action and mode of substrate
      recognition. It appears that Glu 22 acts as an acid and Asp 40 serves as a
      general base to activate a water molecule for an SN2 attack on the glycosidic
      bond. A series of amino-acid side chains and backbone carbonyl groups may bind
      the polycationic chitosan substrate in a deep electronegative binding cleft.

PMID- 8564543
TI  - Crystal structure of the neurophysin-oxytocin complex.
AB  - The first crystal structure of the pituitary hormone oxytocin complexed with its
      carrier protein neurophysin has been determined and refined to 3.0 A resolution.
      The hormone-binding site is located at the end of a 3(10)-helix and involves
      residues from both domains of each monomer. Hormone residues Tyr 2, which is
      buried deep in the binding pocket, and Cys 1 have been confirmed as the key
      residues involved in neurophysin-hormone recognition. We have compared the bound
      oxytocin observed in the neurophysin-oxytocin complex, the X-ray structures of
      unbound oxytocin analogues and the NMR-derived structure for bound oxytocin. We
      find that while our structure is in agreement with the previous crystallographic
      findings, it differs from the NMR result with regard to how Tyr 2 of the hormone
      is recognized by neurophysin.

PMID- 8564544
TI  - The 2.4 A crystal structure of the bacterial chaperonin GroEL complexed with ATP
      gamma S.
AB  - GroEL is a bacterial chaperonin of 14 identical subunits required to help fold
      newly synthesized proteins. The crystal structure of GroEL with ATP gamma S bound
      to each subunit shows that ATP binds to a novel pocket, whose primary sequence is
      highly conserved among chaperonins. Interaction of Mg2+ and ATP involves
      phosphate oxygens of the alpha-, beta- and gamma-phosphates, which is unique for
      known structures of nucleotide-binding proteins. Although bound ATP induces
      modest conformational shifts in the equatorial domain, the stereochemistry that
      functionally coordinates GroEL's affinity for nucleotides, polypeptide, and GroES
      remains uncertain.

PMID- 8564545
TI  - The cavity in the hydrophobic core of Myb DNA-binding domain is reserved for DNA
      recognition and trans-activation.
AB  - The DNA-binding domain of Myb consists of three imperfect repeats, R1, R2 and R3,
      each containing a helix-turn-helix motif variation. Among these repeats, R2 has
      distinct characteristics with high thermal instability. The NMR structure
      analysis found a cavity inside the hydrophobic core of R2 but not in R1 or R3.
      Here, we show that R2 has slow conformational fluctuations, and that a cavity
      filling mutation which stabilizes the R2 structure significantly reduces specific
      Myb DNA-binding activity and trans-activation. Structural observations of the
      free and DNA-complexed stages suggest that the implied inherent conformational
      flexibility of R2, associated with the presence of the cavity, could be important
      for DNA recognition by Myb.

PMID- 8564546
TI  - Evidence for a double-helical structure for modular polyketide synthases.
AB  - Modular polyketide synthases are multienzymes responsible for the biosynthesis of
      a large number of clinically important natural products. They contain multiple
      sets, or modules, of enzymatic activities, distributed between a few giant
      multienzymes and there is one module for every successive cycle of polyketide
      chain extension. We show here that each multienzyme in a typical modular
      polyketide synthase forms a (possibly helical) parallel dimer, and that each pair
      of identical modules interacts closely across the dimer interface. Such an
      arrangement would allow identical modules to share active sites for chain
      extension, and thus to function independently of flanking modules, which would
      have important implications both for mechanisms of evolution of polyketide
      synthases and for their future genetic engineering.

PMID- 8564547
TI  - Evidence for a three-state model of protein folding from kinetic analysis of
      ubiquitin variants with altered core residues.
AB  - To elucidate the kinetic importance of structural intermediates in single-domain
      proteins, we measured the effect of solution conditions and amino-acid changes at
      a central core residue of ubiquitin (Val 26) on the kinetics of folding and
      unfolding. Kinetic analysis in terms of a sequential three-state mechanism
      provides insight into the contribution of specific interactions within the
      ubiquitin core to the structural stability of the native and intermediate states.
      The observations that disruptive mutations and/or addition of denaturants result
      in an apparent two-state folding process with slower rates is explained by the
      destabilization of a partially folded intermediate, which is in rapid equilibrium
      with unfolded states. The model predicts that under sufficiently stabilizing
      conditions kinetic intermediates may become populated even for proteins showing
      apparent two-state kinetics.

PMID- 8564548
TI  - A canonical structure for the ligand-binding domain of nuclear receptors.

PMID- 8564549
TI  - Wound healing: the role of the macrophage and other immune cells.
AB  - The tissue macrophage has been shown to play a critical role in the wound healing
      process. Through the generation of bioactive substances, macrophages orchestrate
      the complex processes of cellular proliferation and functional tissue
      regeneration within wounds. Recent investigations have enumerated many of the
      specific proteins that are produced by wound macrophages at the site of injury.
      These include the following: 1) chemoattractants that recruit and activate
      additional macrophages at the site of injury, 2) growth factors that promote
      cellular proliferation and protein synthesis, 3) proteases and extra-cellular
      matrix molecules, and 4) factors that may restrain tissue growth once repair is
      completed. The development of therapeutic strategies to modulate wound repair
      continues to utilize key macrophage secretory products.

PMID- 8564550
TI  - Comparative analysis of transcription and protein release of the inflammatory
      cytokines interleukin-1 beta (IL-1 beta) and interleukin-8 (IL-8) following major
      burn and mechanical trauma.
AB  - The precondition for the systematic modulation of host impairing behavior of
      hyperactivated monocytes following trauma is to fully understand the mechanistic
      basis of cellular dysfunction. It was the objective of this study to scrutinize
      the synthesis patterns and the level of regulation of the functionally related
      inflammatory cytokines interleukin (IL)-1 beta and IL-8 under stressful
      conditions. We compared the quantity of cytokine protein release in
      lipopolysaccharide-stimulated in vitro cultures of peripheral blood mononuclear
      leukocytes with the signal intensity of the corresponding detectable mRNAs.
      Fourteen patients with major burn or multiple trauma on consecutive days post
      trauma and healthy volunteers were studied. We saw an almost identical pattern of
      synthesis for both monokines during the time of observation, with a considerable
      impairment until day 5 post-trauma and recovery thereafter. In contrast to IL-1
      beta, a clear concurrence between mRNA signal intensity and the quantity of
      protein release was found in the majority of patients for IL-8. From these data
      we conclude that the launching mechanisms for the de novo synthesis for both
      monokines under stress differ greatly, with IL-8 being clearly regulated on the
      transcriptional level, whereas the downregulation of IL-1 beta occurs, most
      likely, on the post-transcriptional level.

PMID- 8564551
TI  - Human peripheral mononuclear cells do not show proinflammatory patterns of
      cytokine transcription in early trauma: a preliminary report.
AB  - Injury has been hypothesized to cause inflammation through systemic release of
      lipopolysaccharide and pro-inflammatory cytokines, but this has proved difficult
      to demonstrate in humans. We looked for evidence of an inflammatory pattern of
      cytokine gene expression by peripheral blood mononuclear cells (PBM) in six
      polytraumatized patients (ISS = 25 +/- 8) upon ER admission, and in six matched
      healthy controls. PBM tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta,
      IL-4, IL-6, IL-10, and interferon (IFN)-gamma message was assessed by semi
      quantitative reverse-transcription polymerase chain reaction. No increase in
      expression of any of the pro-inflammatory cytokines (tumor necrosis factor-alpha,
      IL-1 beta, or IL-6) was found after trauma, and IFN-gamma tended to decrease. Of
      the immunosuppressive cytokines, IL-10 expression increased 5-fold (p < .05) but
      no change in IL-4 was discerned. This pattern is fundamentally different from the
      cytokine expression patterns expected with sepsis or exposure to
      lipopolysaccharide. These findings are inconsistent with the occurrence of
      systemic endotoxemia and subsequent global immunocyte activation early after
      trauma.

PMID- 8564552
TI  - Beneficial effects of LEX032, a novel recombinant serine protease inhibitor, in
      murine traumatic shock.
AB  - The effects of LEX032, a novel recombinant serine protease inhibitor (i.e.,
      serpin), were investigated in an experimental model of Noble-Collip drum shock.
      Pentobarbital-anesthetized rats subjected to drum trauma and receiving only the
      vehicle, developed severe traumatic shock with hypotension. These traumatized
      rats exhibited a survival time of 135 +/- 29 min, endothelial dysfunction, and a
      significant increase in intestinal myeloperoxidase activity. In contrast, LEX032
      given intravenously (15 mg/kg bolus) resulted in a significant prolongation of
      survival time to 264 +/- 25 min (p < .01), a significant and sustained increase
      in mean arterial blood pressure, and a significant attenuation of intestinal
      myeloperoxidase activity (p < .05). Moreover, administration of LEX032
      significantly preserved superior mesenteric artery (SMA) endothelial function as
      measured by the relaxation response of isolated (SMA) rings to acetylcholine, an
      endothelium-dependent vasodilator (64 +/- 10% vs. 25 +/- 6%, p < .01 compared
      with untreated trauma rats). Vasorelaxation responses to an endothelium
      independent vasodilator, NaNO2, were unchanged in trauma. Our results indicate a
      significant protective role of LEX032 in traumatic shock, based on the
      preservation of endothelial function, reduced neutrophil accumulation in injured
      tissues, and increased survival time. These findings suggest that inhibition of
      serine proteases, some of which are from neutrophils, can be beneficial in
      traumatic shock in rats.

PMID- 8564553
TI  - Changes in inositol 1,4,5-triphosphate binding in microsomal fractions from the
      rat liver during sepsis.
AB  - Inositol 1,4,5-triphosphate has been proposed as a second messenger for calcium
      mobilization. The addition of inositol 1,4,5-triphosphate at a low concentration
      has been shown to cause calcium release from intracellular microsomal stores in
      rat hepatocytes. The effects of sepsis on the inositol 1,4,5-triphosphate binding
      from microsomal fractions of rat liver were investigated. Sepsis was induced by
      cecal ligation and puncture (CLP). Control rats were sham operated. Three
      microsomal fractions (rough, intermediate, and smooth I) were isolated from the
      rat liver. The study of inositol 1,4,5-triphosphate receptor binding was
      performed with tritium-labeled inositol 1,4,5-triphosphate. Our results showed
      that the Bmax of inositol 1,4,5-triphosphate binding in early septic, late
      septic, and control groups was 14.9 +/- .9 fmol/mg, 9.8 +/- 1.0 fmol/mg, and 17.2
      +/- 1.3 fmol/mg, respectively. The binding activity was unaffected during early
      sepsis but was significantly depressed by 40-50% (p < .05, vs. control) during
      late sepsis (18 h after CLP) in all three subfractions of endoplasmic reticulum.
      Because the inositol 1,4,5-triphosphate binding plays an important role in the
      regulation of intra-cellular calcium homeostasis in hepatocytes, an impairment of
      the calcium release due to depressed inositol 1,4,5-triphosphate binding in the
      endoplasmic reticulum may have a pathophysiological significance in contributing
      to altered hepatic metabolism during septic shock.

PMID- 8564554
TI  - Attenuation of hepatic neutrophil sequestration by anti-CINC antibody in
      endotoxic rats.
AB  - Cytokine-induced neutrophil chemoattractant (CINC) is a member of the chemokine
      alpha sub-family. It is induced in rats by tumor necrosis factor-alpha (TNF
      alpha), interleukin-1, and lipopolysaccharide and is implicated in neutrophil
      infiltration in response to inflammatory stimuli. We tested the hypothesis that
      pretreatment with anti-CINC antibody or by cobra venom factor attenuates hepatic
      neutrophil accumulation induced by a 90 min infusion of Escherichia coli
      endotoxin. Changes in the expression of CD11b/c and CD18 and in plasma TNF-alpha
      levels were also investigated. Cultured hepatocytes and Kupffer cells of
      endotoxic rats produced significantly more CINC than those of saline-infused
      controls. CINC generation by Kupffer cells was much lower than generation by
      hepatocytes. Pretreatment with anti-CINC antibody or cobra venom factor
      significantly reduced hepatic neutrophil sequestration, but did not affect the up
      regulation of CD11b/c and CD18 expression on liver-sequestered neutrophils or
      plasma TNF-alpha levels. We conclude that CINC-mediated hepatic neutrophil
      accumulation may not be necessarily associated with up-regulation of neutrophil
      adhesion molecules or elevated circulating TNF-alpha levels. Attenuation of
      hepatic neutrophil sequestration by anti-CINC antibody is likely based on
      blocking of the chemotactic activity of CINC and thus diminishing the chemotactic
      gradient established in the liver.

PMID- 8564555
TI  - Sustained elevation in circulating catecholamine levels during polymicrobial
      sepsis.
AB  - Although studies have indicated that the levels of catecholamines increase during
      sepsis, it remains unknown whether the elevated levels of epinephrine,
      norepinephrine, and dopamine observed in early sepsis are sustained during late,
      hypodynamic stages of sepsis. In this study, rats were subjected to sepsis by
      cecal ligation and puncture (CLP, i.e., polymicrobial sepsis). Immediately after
      CLP or sham operation, animals received 3 mL/100 g body weight normal saline
      subcutaneously. At .5, 2, 10 (i.e., early sepsis), or 20 h (late sepsis) after
      CLP, blood samples were drawn and the plasma was separated. Plasma levels of
      epinephrine, norepinephrine, and dopamine were determined using a [3H]
      radioenzymatic assay. The results indicate that plasma levels of epinephrine,
      norepinephrine, and dopamine increased significantly as early as .5 h after CLP.
      The increase in catecholamine levels persisted throughout the study periods.
      Thus, circulating levels of catecholamines were elevated in both early and late
      stages of polymicrobial sepsis. These results suggest that the increased
      catecholamine levels at .5-10 h after CLP may contribute to the hypermetabolic
      conditions that occur during early, hyperdynamic sepsis. However, there is a lack
      of an association between the elevated plasma catecholamine levels and
      hypometabolic/hypodynamic state in late sepsis.

PMID- 8564556
TI  - S-ethylisothiourea, a nonamino acid inhibitor of nitric oxide synthase, reverses
      septic vasodilation in sheep.
AB  - S-ethylisothiourea (3936W92) is a nonamino acid antagonist of nitric oxide
      synthase. Its selectivity for the inducible form of nitric oxide synthase is
      twice as high as for the constitutive form of the enzyme. We tested 3936W92 in 20
      sheep, which were surgically prepared for chronic study. In all sheep, a
      hyperdynamic sepsis was induced by a continuous infusion of live Pseudomonas
      aeruginosa. After 24 h of sepsis, nine sheep received a continuous infusion of
      3936W92 over the next 24 h, whereas the control group (n = 9) received saline
      instead. Two sheep died within the first 24 h of sepsis. 3936W92 caused a
      complete reversal of the hyperdynamic circulation, while sheep in the control
      group remained hyperdynamic. Although the cardiac index decreased significantly
      during treatment with 3936W92 (7.9 +/- .8 vs. 6.0 +/- .7 l/min/m2), a
      simultaneous increase in oxygen extraction prevented oxygen consumption from
      falling.

PMID- 8564557
TI  - Inhibition of nitric oxide synthesis aggravates reperfusion injury after hepatic
      ischemia and endotoxemia.
AB  - The potential role of nitric oxide (NO) was investigated in the pathophysiology
      of liver injury after priming with 20 min hepatic ischemia-reperfusion and
      administration of .5 mg/kg Salmonella enteritidis endotoxin. Liver injury during
      the early reperfusion phase of 4 h was characterized by severe vascular oxidant
      stress, lipid peroxidation (LPO), neutrophil infiltration, and a 33% reduction of
      the microvascular blood flow in the liver. Inhibition of NO synthesis with N
      omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) aggravated liver
      injury by 90%, reduced LPO, and did not affect liver neutrophils but further
      impaired microvascular blood flow. Treatment with the NO-donor spermine-NONOate
      or L-arginine did not affect these parameters in postischemic animals, however,
      treatment did restore all values of L-NAME-treated animals back to disease
      control levels. These data suggest that endogenous NO formation is sufficient to
      limit ischemic liver injury during reperfusion but inhibition of NO synthesis
      will result in additional ischemic damage. NO may also be involved in scavenging
      of superoxide in the vasculature and in inducing LPO.

PMID- 8564558
TI  - Sustained 35-GHz radiofrequency irradiation induces circulatory failure.
AB  - The objective of this study was to determine the thermal distribution and
      concomitant cardiovascular changes produced by whole-body exposure of ketamine
      anesthetized rats to radiofrequency radiation of millimeter wave (MMW) length.
      Rats (n = 13) were implanted with a flow probe on the superior mesenteric artery
      and with a catheter in the carotid artery for the measurement of arterial blood
      pressure. Temperature was measured at five sites: left (Tsl) and right
      subcutaneous (sides toward and away From the MMW source, respectively), colonic
      (Tc), tympanic, and tail. The animals were exposed until death to MMW (35 GHz) at
      a power density that resulted in a whole-body specific absorption rate of 13
      W/kg. During irradiation, the Tsl increase was significantly greater than the Tc
      increase. Heart rate increased throughout irradiation. Mean arterial pressure
      (MAP) as well maintained until Tsl reached 42 degrees C, at which point MAP
      declined until death. Mesenteric vascular resistance tended to increase during
      the early stages of irradiation but began to decrease at Tsl > or = 41 degrees C.
      The declines in both mesenteric vascular resistance and MAP began at Tc < 37.5
      degrees C; death occurred at Tc = 40.3 +/- .3 degrees C and Tsl = 48.0 +/- .4
      degrees C. These data indicate that circulatory failure and subsequent death may
      occur when skin temperature is rapidly elevated, even in the presence of
      relatively normal Tc.

PMID- 8564559
TI  - Inhibition of pulmonary hypertensive response after antigen challenge.
AB  - By adding antigen cells into perfusate circulation, a great increase in pulmonary
      arterial pressure was observed in isolated perfused lung from rabbits previously
      immunized with human O-N type erythrocytes. To investigate whether thromboxane A2
      is the main mediator in pulmonary vasoconstrictive response, we injected antigen
      erythrocytes into the reservoir after administration of putative inhibition as
      follows: indomethacin (5 mg/kg, thromboxane A2 synthetase inhibitor), KT2-962 (.1
      mg/kg, thromboxane receptor blocker), and pyrilamine (.1 mumol, H1 blocker).
      Pulmonary vasoconstrictive response after antigen challenge was significantly
      blocked by both indomethacin and KT2-962, but not by H1 blocker. Although the H1
      blocker, pyrilamine, did not significantly block the pulmonary vasoconstrictive
      response, it did significantly block the bronchoconstrictive response after
      antigen challenge; however, the bronchoconstrictive response was not blocked by
      either indomethacin or KT2-962. We conclude that thromboxane is the main mediator
      in the pulmonary vasoconstrictive response, and histamine is the main mediator in
      the bronchoconstrictive response.

PMID- 8564560
TI  - The recombinant 23-kDa N-terminal fragment of bactericidal/permeability
      increasing protein (rBPI23) decreases Escherichia coli-induced mortality and
      organ injury during immunosuppression-related neutropenia.
AB  - Cyclophosphamide-induced neutropenia exacerbates septic shock and multiple organ
      injury in conscious rats during Escherichia coli (EC) bacteremia despite
      antibiotics and fluid administration. We hypothesized that such shock and
      inflammatory organ injury would be mitigated by rBPI23's microbicidal activity
      and/or binding of EC endotoxins. Four days after 100 mg cyclophosphamide/kg,
      catheterized rats with < 300 PMNs/microL were pretreated with rBPI23 or the
      irrelevant 22 kDa protein thaumatin [3.3-6.6 mg/kg, i.v. in 0.9% NaCl (NS)] 5 min
      before graded i.v. infection with 5 x 10(9) or 1 x 10(10) cfu of EC serotype
      055:B5 ending at t = 0. Posttreatment with each protein continued (3.3-6.6 mg/kg
      in 1 mL NS/h) through 8 h, in addition to penicillin plus amikacin sulfate at t =
      1.5 and 8 h. Arterial samples were obtained before pretreatment and at t = 1.5,
      4.5, 8, and 24 h when animals were necropsied. One of eight thaumatin + 5 x 10(9)
      EC rats and none of six thaumatin + 10(10) EC rats survived 24 h. In contrast,
      rBPI23 significantly reduced mortality after either inoculum, improved bacterial
      clearance, and led to renormalization of early EC-induced hypotension,
      hypothermia, tachypnea, hyperoxemia, and hypocarbia. Compared with thaumatin,
      however, rBPI23 did not reduce circulating endotoxin or bioactive and antigenic
      tumor necrosis factor-alpha. Sepsis-induced severe neutropenia (< 50 PMNs/microL)
      evident in all EC rats by t = 1.5 h was reversed with rBPI23 by t = 8 h, but
      thrombocytopenia (< 5 x 10(4) platelets/microL) evident in all groups by t = 4.5
      h was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8564561
TI  - Macro- and microcirculatory effects of IL-15.
AB  - The recently isolated and cloned cytokine interleukin (IL)-15 was studied to
      ascertain its systemic and local cardiovascular effects. IL-15 was studied in
      rats anesthetized with 50 mg/kg sodium pentobarbital. In Group I, 10-50
      micrograms of IL-15 were administered intravenously. Heart rate and arterial
      pressure decreased significantly for the duration of the study. In Group II, IL
      15 was administered topically to the exposed cremaster muscle in four doses of 10
      ng each. Heart rate and arterial pressure decreased significantly for the
      duration of the study. A1 and A2 arteriolar diameters decreased, but A3 diameters
      remained unchanged as determined by videomicroscopy. Vasodilation induced by
      either topical acetylcholine or nitroprusside was abolished by IL-15. Reduced
      heart rate and arterial pressure suggest reduced cardiac output. Arteriolar
      constriction due to abolished smooth muscle dilation was caused by IL-15.

PMID- 8564562
TI  - [Jean-Claude Dreyfus (1916-1995)].

PMID- 8564563
TI  - [Nuclear receptors and ontogenesis of the hematopoietic tissue].
AB  - Differentiation of the hematopoietic tissue is controlled by growth factors which
      act precisely on stem cells arriving at a specific stage of differentiation. The
      recent identification of retinoic acid, a vitamin A metabolite, as an active
      differentiating agent of acute promyelocytic leukemia, has allowed to define a
      normal group of growth and differentiation factors of the myeloid tissue:
      vitamins A and B and thyroid hormones.

PMID- 8564564
TI  - [Acute promyelocytic leukemia: molecular aspects].
AB  - Acute promyelocytic leukemia is a key model system in Cancer biology. Its ability
      to differentiate upon exposure to retinoic acid constitutes the first example of
      differentiation therapy. The molecular basis of leukemogenesis is the PML/RAR
      fusion resulting from the t(15, 17) translocation. The fusion protein likely acts
      through interference with the function of nuclear receptors (resulting in a
      differentiation block) and also through interference with PML which appear to be
      a growth suppressor. The exquisite sensitivity of this disease to retinoic acid
      represents the first example of a therapy directly targeted at a specific and
      causative genetic lesion.

PMID- 8564565
TI  - [Treatment of acute promyelocytic leukemia by all trans retinoic acid].
AB  - It has been shown in vitro that retinoids and especially all-trans retinoic acid
      (ATRA) were able to induce maturation of malignant cells from patients with acute
      promyelocytic leukemia (APL). Clinical studies have confirmed in vitro
      observations. Oral administration of ATRA is able to induce complete remissions
      in the majority of APL patients, either treated de novo or after failure of
      conventional chemotherapy. Complete remission are observed by a differentiation
      process and ATRA therapy in APL represents the first model of differentiation
      therapy. The major adverse effect of ATRA treatment is the occurrence in some
      cases of a "retinoic acid syndrome" associated with rapidly, progressive rise of
      leukocytes. This syndrome is corrected by the addition of chemotherapy. A
      progressive acquired resistance appears during ATRA treatment and for this reason
      post remission chemotherapy is indispensable. The superiority of the combination
      of ATRA+chemotherapy over chemotherapy alone for the incidence of relapse and for
      survival duration has been established in a randomized European trail (APL 91).

PMID- 8564566
TI  - [Effect of translocation t(15;17) on the gene expression regulation of
      myeloblastin during all trans retinoic acid induced myeloid differentiation in
      human leukemic cells].
AB  - Myeloblastin (mbn) is a serine protease involved in the control of growth and
      differentiation of human leukemic cells. In the promyelocytic-like human leukemia
      cell line HL-60 this protease is inhibited during retinoic acid (RA) induced
      differentiation. The t(15;17) translocation, specifically associated with the
      human acute promyelocytic leukemia (APL), fuses the retinoic acid receptor alpha
      (RAR alpha) to a novel gene PML generating the hybrid protein PML-RAR. We have
      shown that while mbn was early down-regulated in HL60 cells treated with all
      trans RA, the inhibition of this gene was considerably delayed in NB4 cells,
      which carry the t(15;17) translocation, upon treatment with the same inducer.
      This observation suggested that the changes in the myeloblastin regulation by RA
      found in NB4 cells could be ascribed to the presence of the fusion protein PML
      RAR. To verify this hypothesis we have cloned the putative promoter region of mbn
      gene. Transactivation properties of endogenous retinoic acid receptors on this
      region have been tested in transfection experiments of HL60 and NB4 cell lines
      before and after treatment with all trans RA. We found that RA induced a
      significant inhibition of the luciferase reporter gene in HL60 cells. In
      contrast, a strong stimulation of luciferase activity was observed in NB4 cells
      treated with RA. The analysis of the promoter region allowed us to identify a new
      response element for retinoic acid receptors, named mREpal, which is probably
      affected by the product of t(15;17) translocation.

PMID- 8564567
TI  - [Cytokines in inflammation].
AB  - Numerous cytokines are present within inflammatory foci. Interleukin-1 (IL-1) and
      tumour necrosis factor (TNF) play a major role in coordinating mechanisms which
      command inflammation. Upon their action, many different cells produce lipidic
      mediators, proteolytic enzymes, and free radicals, all directly responsible for
      the noxious effects observed. IL-1 and TNF exert cytotoxic effects on vascular
      endothelium, cartilage, bone and muscle. Such cytokines as interferon-gamma, IL-3
      or granulocyte-macrophage colony stimulating factor amplify the inflammatory
      response by increasing the production of IL-1 and TNF. The latest trigger the
      release of chemokines such as IL-8 and macrophage chemoattractant protein-1, the
      chemotactic activity of which participates in the recruitment of leukocytes
      within the foci of inflammation. IL-6, abounds in inflammatory processes and
      induces the production by hepatocytes of acute phase proteins. The same applies
      to IL-1, TNF, IL-11, the leucocyte inhibitory factor, and the transforming growth
      factor-beta. The later also processes a number of anti-inflammatory activities
      and, like IL-4, IL-10 and IL-13, can inhibit IL-1 and TNF production. Such
      property has also been mentioned for interferon-alpha. These anti-inflammatory
      cytokines can also counteract some of the IL-1 and TNF activities such as those
      reported during the coagulation process. Furthermore, these anti-inflammatory
      cytokines can induce the production of the IL-1 receptor antagonist which
      prevents the activities initiated by IL-1. Soluble TNF receptors, released during
      inflammation, are the direct inhibitors for TNF. Glucocorticoids, produced
      following a cascade of events initiated by IL-1, TNF and IL-6, involving the
      neuroendocrine axis, also inhibit proinflammatory cytokine productions. The
      concept of "cytokine network" therefore, perfectly illustrates the participation
      of these mediators in inflammation mechanisms.

PMID- 8564568
TI  - [Exploration of cytokines in inflammation in biological fluids].
AB  - Accurate and sensitive methods for the measurement of acute phase cytokines (IL
      1, IL-6, IL-8, TNF alpha, LIF) in biological fluids are an absolute prerequisite
      for a proper use of these mediators in clinical practice. Nowadays, numerous kits
      are commercially available for cytokines quantitation, but one must be very aware
      of the difficulties in the study of these molecules. The authors describe the
      various molecular forms under which cytokines can possibly circulate. The
      potential influence of inhibitors (autoantibodies, soluble receptors) on cytokine
      assays is discussed. Blood collection for cytokines needs a particular attention
      to prevent a possible contamination by endotoxins which can trigger cytokines
      cellular production after sampling. If bioassays historically preceded
      immunoassays, these last techniques are now very popular, but there is an urgent
      need for standardisation between the different kits commercially available. In
      addition, the study of the ability of cells to produce cytokines and the in situ
      detection of cytokines using molecular biology constitute helpful complementary
      techniques to the measurement of circulating cytokines.

PMID- 8564569
TI  - [Inflammatory process, histopathological aspects].
AB  - Inflammation occurs only in conjunctive tissue and is the result of a close
      cooperation of various cells: blood platelets, endothelial cells, leucocytes,
      mast cells, fibroblasts. Successive phases can be recognized, the first is
      characterized by vascular phenomenons defining the acute phase. The second by
      cellular reactions defining the chronic or granulomatous phase. Various
      morphological patterns can be recognized in acute or chronic inflammation. In
      addition, hypersensitivity is responsible of peculiar morphology of the
      inflammatory response. After tissue necrosis, tissular debris should be
      eliminated by detersion. Then, a granulation tissue develops representing the
      first step of the healing, which will not be described here.

PMID- 8564570
TI  - [Acute-phase proteins in inflammation].
AB  - The acute phase proteins (APPs) have been empirically defined as those whose
      plasma concentration changes following inflammatory reaction. Those proteins
      whose concentrations increase are referred to as positive APP, while those whose
      levels decline are termed negative APP. In man, positive APP are: alpha 1 acid
      glycoprotein, alpha 1 protease inhibitor, alpha 1 antichymotrypsin, haptoglobin,
      ceruloplasmin, fibrinogen, C-reactive protein, serum amyloid A. Great variability
      in the APP response between different species is observed. The principal
      functions of APP, result from the interaction of these proteins with ligands of
      various origins which give "protein-ligands" complexes. These complexes are
      cleared by the RES or by the hepatocyte. The results are protease inhibition,
      neutralization of toxic molecules such as hemoglobin or the superoxide anion,
      clearance of cell membranes and chromatin. The drop of the plasma concentration
      of negative APP during an inflammatory reaction carries a rise of free ligands
      (fatty acids, hormones, vitamins, trace elements). IL6 has been recognized as the
      principal regulator of most APP genes. The response of the hepatic cell to IL6 is
      characterized by the enhanced production of type 2 or IL6 specific APPs. The
      biochemical process of signal transduction is IL6--JAK2--APRF The set of APP
      genes regulated by IL1 type cytokines (type 1 APPs) is distinct from that
      regulated by IL6 type cytokine. IL1 and TNF alpha mediated stimulation of type 1
      APP genes is synergistically enhanced by IL6 type cytokines. The biochemical
      process of signal transduction is IL1, IL6--Ras--MAP kinase--NFIL6 The targeted
      inflammatory proteic profile including the assay of C-reactive protein,
      haptoglobin and alpha 1 acid glycoprotein produces a "biological tool" to the
      clinician in order to manage an inflammatory response. IL6, a proteic marker for
      the future, connected with CRP, will be assayed during early inflammatory
      reaction.

PMID- 8564571
TI  - [Treatment of inflammation with anti-inflammatory cytokines: example in models of
      auto-immune diseases].
AB  - Cytokines may exert anti-inflammatory properties, allowing the hypothesis of
      their potential therapeutic use. Targeting the cytokines balance may modify the
      course of subsequent inflammatory events in an autoimmune disease. Many data are
      available. Interferon-gamma can be blocked by an anti-interferon-gamma monoclonal
      antibody: if the treatment is administered in the early phase of an autoimmune
      disease such as collagen-induced arthritis, the course of the disease is
      worsened; if the treatment is given later, the disease can be improved; these
      results are mirrored by treatment with high doses of the cytokine itself.
      Pharmacologic effects of antiinflammatory cytokines such as interleukin (IL)-4,
      IL-10 or IL-13 are a protection against several experimental autoimmune diseases.
      The very short half-life of cytokines makes them difficult and expensive to use
      directly; in such occurrence, high quantities have to be frequently injected. In
      this context, gene therapy appears as an effective alternative solution: the
      transfection of cells with cytokines genes (e.g. either IL-4 or IL-13) then the
      engraftment of these vectors in animals, permit the in vivo secretion of high
      levels of cytokines, and result in the protection of the animals from the
      development of the disease.

PMID- 8564572
TI  - [Do several waves of stem cells follow themselves during hematopoietic
      development?].
AB  - Chimeras built between a quail embryo and a chick yolk sac have led to the
      demonstration that, in the avian model, intra-embryonic hemopoietic stem cells
      (HSC) relay HSC originating from the yolk sac. Converging experimental approaches
      have localized the emergence of intraembryonic HSC to the region of the aorta.
      Today's session will be dedicated to reviewing experimental data in mouse and man
      that clearly indicate that this model of hemopoietic ontogeny is also operating
      in mammals.

PMID- 8564573
TI  - [Clinical use of placental blood cells].
AB  - Human cord and placental blood provides a rich source of hematopoietic stem
      cells. On the basis of this finding, umbilical cord blood stem cells have been
      used to reconstitute hematopoiesis in children with malignant and non malignant
      diseases after treatment with myeloablative doses of chemoradiotherapy. Early
      results show, that a single cord blood provides enough hematopoietic stem cells
      to provide short and long term engraftment, that the incidence and severity of
      graft versus host disease has been low even in HLA mismatched transplants. These
      results are encouraging enough, to embark on large scale banking of cord blood
      for purposes of future allogeneic and autologous stem cell transplantation, to
      promote studies on the unique properties of fetal and neonatal hematopoiesis, to
      study the immunological properties of cord blood cells, to initiate
      investigations on gene transfer into human cord blood cells for future gene
      therapy trials. This review will briefly summarize the current knowledge on cord
      blood transplantation as well as the future development of research on this
      unique source of hematopoietic stem cells.

PMID- 8564574
TI  - [Early ontogeny of the human hematopoietic system].
AB  - Immunohistochemistry was used to detect markers of the vascular, stromal and
      hematopoietic cell compartments in the human embryo and early fetus, from 3 to 15
      weeks of gestation. CD34 expression was consistently observed at the surface of
      vascular endothelial cells from off earliest stages tested, at the single
      exception of embryonic liver blood vessels. Yolk sac hematopoiesis was very
      transient and limited to primitive erythropoiesis. Clusters of erythroblasts,
      monocytes and granulocytes appeared from 4 to 5 weeks of gestation in the liver
      rudiment. The early development of the bone marrow was marked by the rapid
      invasion, at 8 weeks, of long bone cartilaginous rudiments by CD68+ osteoclast
      precursors, CD34+ endothelial cells and by preosteoblasts, leading to the
      development of large vascular sinuses between ossifying trabeculae. Endogenous
      erythro- and granulopoiesis developed from week 11 in primary logettes always
      organized around an arteriole, in a loose stromal mesenchymal network established
      between the media of these arterioles and the sinusal endothelium. Round,
      hematopoietic CD34+ cells were seen occasionally in yolk sac blood vessels. In
      the liver they were rare and intermingled as single cells in the hepatocyte
      cords; strikingly, CD34+ hematopoietic cells could seldom be detected in the
      developing bone marrow. In contrast, compact clusters of non-endothelial, round
      CD34+ CD45+ hematopoietic cells were detected, during the 5th week of
      development, in close association with the ventral wall of the dorsal aorta.
      These cells exhibit phenotypic and functional characteristics of very primitive
      hematopoietic progenitors. This observation is in striking correlation with the
      evidence accumulated in animal models that stem cells for the late embryonic and
      adult hematopoietic systems develop inside the embryo per se, in the vicinity of
      the dorsal aorta. We thus suggest that these aorta-associated CD34+ cells, that
      exhibit an anatomic localization similar to that of the intraembryonic stem cells
      identified in the avian and murine embryo, are the real stem of human
      hematopoiesis.

PMID- 8564575
TI  - [Characterization of hematopoietic progenitor cells during the human embryonic
      development].
AB  - In a search for assays that might facilitate identification of pluripotent stem
      cells with extended potentialities, we analysed the properties of hematopoietic
      progenitor cells detected in the extraembryonic yolk sac and in the
      intraembryonic part of human embryos between approximately 28 and 45 days of
      development. Cells from the yolk sac, the liver rudiment and the remainder of the
      embryo were plated in semi solid methylcellulose colony-assays supplemented with
      combinations of cytokines. Large BFU-E-derived colonies as well as granulocytic
      colonies were detected in every yolk sac sample. Interestingly, progenitor cells
      were also detected in the intraembryonic part, outside the liver and a subclass
      of these progenitors were detected that generated large granulomacrophagic
      colonies capable of generating secondary colonies when replated. These were
      preferentially located in the embryo. Colony-assays initiated with CD34+ cells
      sorted from the different tissues confirmed these data. These results first
      indicate that embryonic progenitors exhibit unique phenotypic features, and
      second, analysis of the distribution of progenitors between the different tissues
      may suggest the existence of other sites of hematopoietic production. More
      detailed analysis of the potentialities of these progenitors should now be
      assessed in vitro in cocultures assays and in vivo by reconstituting
      immunodeficient mice.

PMID- 8564576
TI  - [Intra-embryonic hematopoiesis in mice].
AB  - In vertebrate embryos, all hemopoietic tissues that are successively active
      during ontogeny (fetal liver, thymus, spleen and bone marrow) are colonized by
      extrinsic hemopoietic stem cells (HSC). The exception to this rule is the yolk
      sac (YS) whose progenitors arise in situ. Moreover, the YS is the first
      hemopoietic site to appear in the embryo. In consequence, it was considered as
      the primary source of the HSC that transfer from one site to the other until the
      demonstration that, in birds, the source of definitive HSC was located in the
      aortic region of the embryo. To assess a possible contribution of intraembryonic
      sites to mouse hemopoietic development, we developed an in vitro approach that
      permits the detection of multipotent hemopoietic progenitors in the region
      surrounding the dorsal aorta. This new site, the paraaortic splanchnopleura (P
      Sp), is active from the 10 somite stage to the stage of fetal liver colonization
      by HSC. The in vitro analysis of the hemopoietic potential of the P-Sp revealed
      that: 1) progenitors present in this region are multipotent since a single
      micromanipulated P-Sp cell can give rise to mature B and T lymphocytes and
      various myeloid cells, when cultivated in appropriate conditions; 2) the P-Sp is
      the only intraembryonic site endowed with this potential; 3) numbering
      progenitors present in the YS and P-Sp indicated that precursors appear in both
      locations at the 10-12 somite stage reaching 15 in each site at 9.5 dpc (25
      somites), shortly before the beginning of fetal liver colonisation. During a
      cytological study of the 9-11 dpc embryo aimed to disclose the cellular basis for
      our experimental results, two potential hemopoietic sites were uncovered. Cells
      clusters that resemble avian intraaortic hemopoietic clusters were found in the
      arteries located close to the coelomic cavity (dorsal aorta, umbilical and
      omphalomesenteric arteries). Moreover, groups of cells strikingly similar to YS
      blood islands were uncovered in the mesentery. All these sites are located in
      areas formed from the P-Sp and are fully developed at the onset of fetal liver
      colonization. These hemogenic sites most probably develop from the hemopoietic
      precursors present in the P-Sp.

PMID- 8564577
TI  - [Study of mitochondrial DNA in Helix land snails by PCR-RFLP].
AB  - Sometimes the morphological criteria--used to distinguish between 4 land snails
      species (Helix pomatia, Helix lucorum, Helix aspersa aspersa and Helix aspersa
      maxima)--are little pronounced and ambiguous. We have selected mitochondrial DNA,
      a widely used molecular marker, in order to have a reliable technique of
      distinction between the 4 studied species. After extraction, mtDNA is amplified
      by PCR and digested with several enzymes. Among them, Dra I give restriction
      fragments of different length depending on species. So, owing to PCR-RFLP of
      mtDNA, we describe here a reliable method for identifying 4 snail species.

PMID- 8564578
TI  - [Epidermal growth factor (EGF) can induce prostatic buds in the absence of
      androgens].
AB  - We have investigated the prostatic bud induction in the urogenital sinus of fetal
      rats and mice when the sinuses were cultured with non-androgenic growth factors,
      and found that epidermal growth factor (EGF) as well as transforming growth
      factor-alpha (TGF-alpha) powerfully induces the prostatic buds in the absence of
      androgens even in the androgen-receptor-deficient Tfm sinuses. Immunofluorescence
      study revealed that endogenous EGF and EGF receptor exist in the sinus mesenchyme
      of 19.5-day fetal male rats, where many prostatic buds are appearing.

PMID- 8564579
TI  - [In vitro study of the metabolic conversion of aflatoxin B1 into its epoxide].
AB  - The conversion of aflatoxin B1 into its epoxide was evaluated in vitro by two
      different approaches based on HPLC analysis: the quantitative estimation of the
      tris(OH)AFB1 addition product resulting from the indirect reaction of AFB1
      epoxide with tris buffer (hydroxymethyl) aminomethane and on the other hand by
      the quantification of the formation of the glutathione conjugate (AFB1-SG). The
      tris(OH)AFB1 is more sensitive than AFB1-SG in fluorescence detection. The AFB1
      SG obtained (5.42 +/- 0.42 microgram) is weakly less than the quantity of
      tris(OH)AFB1 (6.00 +/- 0.72) obtained in the same experimental conditions.

PMID- 8564580
TI  - [Lactate as competitive inhibitor of Pinus pinea isocitrate lyase].
AB  - We studied the effect of L-lactate on both the cleavage and the condensation
      reactions of Pinus pinea isocitrate lyase. This compound is a competitive of
      Pinus pinea isocitrate lyase towards both isocitrate and glyoxylate, whereas is a
      mixed type inhibitor towards succinate. Assuming that L-lactate acts as a
      glyoxylate analogue, our finding agrees with an uni-bi ordered mechanism of
      isocitrate lyase, with glyoxylate first substrate to enter the active site in the
      condensation reaction. Results are discussed and compared with those known in the
      literature about other structurally related metabolites.

PMID- 8564581
TI  - [Zinc phytotoxicity and induction of stress proteins in bean (Phaseolus vulgaris
      L.)].
AB  - Bean seedlings (Phaseolus vulgaris L., cv. fin de Bagnol) were grown for ten days
      in nutrient solutions at 0, 50, 100, 500 and 1000 microM ZnS0(4). The results
      obtained show that Zn treatment is followed by a pathological behaviour, the
      precocity and intensity of which are dependent on the applied dose. In addition
      to the depressive effects on the biomass yield and the tissue water content, a
      decrease in the proteins contents was also observed. Zinc toxicity seems to
      induce synthesis of low molecular weight proteins in Zn-treated bean stems, but
      not in the roots and leaves. These peptides, in stems, may protect,
      hypothetically, the susceptibles metabolic sites in foliar parenchyma against the
      zinc deleterious effects.

PMID- 8564582
TI  - [Use of cell culture for the research of cytotoxic and antiviral effects of a
      natural extract of Amaryllidaceae].
AB  - The use of tissue culture for evaluation of antiviral agents can provide rapid
      information on the toxicity induced by drugs. Toxicity is assessed through 4
      different tests: observation through a light microscope, colorimetric evaluation
      of living cells stained with MTT (Methyl Thiazol Tetrazolium), colorimetric
      evaluation of fixed cells stained with crystal violet, inhibition of
      incorporation of radioactive labelled precursors specific to the synthesis under
      study. These tests allowing evaluation of effects on cell morphological changes
      (1), of modifications of mitochondrial and enzymatic activities in the cytoplasm
      (2), of effects on cell growth (3) and on their major synthesis [ADN, ARN,
      proteins] (4). This design of experiments has been applied to an hydroalcoolic
      extract from Haemanthus albiflos (Amaryllidaceae) tested for its antiviral
      properties towards Poliovirus type 1 propagated on monkey kidney cells line (MA
      104). The maximum tolerated dose by the cell and the inhibition of virus
      replication were determined according to tests 2 and 3. The sensitive step of the
      virus replication cycle was investigated using test 4. Concentration of 7
      microliters/ml plant extract showed: 20% cytotoxicity (MTT test). At 7
      microliters/ml plant extract the inhibition of replication virus is 4.5 log units
      (microplates assay) and inhibition of proteins viral synthesis is 97% compared
      with the control.

PMID- 8564584
TI  - Comprehensive guidelines on HIV-related opportunistic infections released.

PMID- 8564583
TI  - Study documents spread of drug-resistant pneumococci.

PMID- 8564585
TI  - Teens cite illicit drugs as major worry, see marijuana as gateway.

PMID- 8564586
TI  - FDA rethinks OTC status of bronchodilators, theophylline labeling.

PMID- 8564587
TI  - Computerized system for physician order entry.

PMID- 8564588
TI  - Strontium chloride Sr 89 for treating pain from metastatic bone disease.
AB  - The role of strontium chloride Sr 89 in the palliative treatment of pain
      associated with metastatic bone disease is reviewed. Conventional therapies to
      relieve metastatic bone pain include nonopioid and opioid analgesics, hormonal
      therapy, external-beam irradiation, and chemotherapy. Limitations in the long
      term safety and effectiveness of these treatments have increased interest in
      using systemic radioactive isotopes for palliation of pain. Strontium chloride Sr
      89 is a relatively new bone-seeking radiopharmaceutical that has FDA-approved
      labeling for use in relieving pain associated with skeletal metastases. An
      analogue of calcium, strontium chloride Sr 89 is rapidly cleared from the blood
      after i.v. injection. The agent selectively irradiates metastatic sites while
      generally sparing normal soft-bone tissue. In clinical studies, a majority of
      patients with prostate or breast cancer obtained substantial relief from bone
      pain after receiving strontium chloride Sr 89 alone or in combination with
      external-beam irradiation. Adverse effects tend to be mild, but patients should
      be monitored for possible hematologic toxicity. Patients should discontinue any
      calcium-containing products before receiving the agent. The typical dose is 4 mCi
      (148 MBq) administered by slow i.v. push over one to two minutes; doses can be
      repeated at three-month intervals. Pain relief usually begins in 10-20 days and
      lasts up to six months. Radiation safety measures are necessary in handling
      strontium chloride Sr 89 and the wastes of patients. Strontium chloride Sr 89 is
      costly, but preliminary analysis indicates that it may reduce management
      expenditures overall.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8564590
TI  - Computer-guided academic detailing as part of a drug benefit program.
AB  - A service for identifying opportunities for drug cost savings in managed care
      plans and intervening by giving drug information to physicians is described. A
      clinical pharmacy company developed a computerized drug-use-review program to (1)
      identify and track variances in prescribing from drug-use criteria, (2) formulate
      plans for correcting the variances, and (3) document the impact of those
      interventions on drug costs. The software program weights prescriptions claims
      data against drug-use criteria to identify opportunities to save money. Savings
      opportunities for drug costs are defined as the net difference between the cost
      of the prescription claim and the lower, criteria-based cost. Episodes of
      potential savings are grouped by variables such as drug, physician, patient, and
      pharmacy, and each group is characterized by its total potential for cost
      savings. The groups are ranked to identify drug therapy problems that most
      contribute to the cost of medication misuse to the client. Pharmacists counsel
      identified physicians and enter the responses into a database for economic
      analyses. From September through December 1993, the software program was used to
      review 167,684 prescription claims totaling $4,368,576 in drug expenditures for
      enrollees in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly
      program. Potential drug cost savings totaling nearly $280,000 were identified.
      Academic detailing by the company's pharmacists resulted in a saving in drug
      costs of more than $12,000 per month for the first three months after the
      detailing. Pharmacists at a clinical pharmacy company decreased drug costs for a
      managed care organization by using a software program to identify the drug costs
      with the greatest potential for savings and the physicians associated with those
      costs; the physicians were targeted for academic detailing.

PMID- 8564589
TI  - Failure of educational videotapes to improve medication compliance in a health
      maintenance organization.
AB  - The value of mailed educational videotapes as a means of enhancing compliance
      with drug therapy was studied. Members of a health maintenance organization with
      a pharmacy claim for benazepril, metoprolol, simvastatin, or transdermal estrogen
      were randomly assigned to a study group or a control group. Subjects in the study
      group were mailed one of four videotape programs giving information on the drug
      prescribed and the inferred disease state. Control subjects received no
      educational materials. Subjects were enrolled from July 1, 1993, through January
      2, 1994. Refill data were collected from July 1, 1993, through April 1, 1994. The
      medication possession ratio (MPR) was calculated as the total number of days'
      supply of a drug obtained by a member divided by the number of days between the
      time of enrollment and April 1, 1994, or the date the member was terminated from
      the plan. A subject was deemed compliant if his or her MPR was > or = 0.80. There
      were no significant differences in mean MPRs between the study group (n = 1993)
      and the control group (n = 2253). None of the mean MPRs was > or = 0.80, although
      44% of control subjects and 46% of study-group subjects were compliant. Of 97
      respondents to a survey mailed to a randomly selected subset of the study group,
      almost 87% reported that they had viewed the videotapes, and of these subjects,
      about 88% said they found them very useful or somewhat useful. A one-time mailing
      of videotapes to patients, with no individual follow-up, did not increase
      compliance with the medications monitored.

PMID- 8564591
TI  - Stability of cyclosporine in an extemporaneously compounded paste.
AB  - The stability of cyclosporine in an extemporaneously compounded paste was
      studied. Cyclosporine oral solution 100 mg/mL was mixed with an adhesive gel to
      prepare six aluminum-lined ointment tubes containing paste with cyclosporine 9.6
      mg/g. Two of the tubes were stored at 37 degrees C, two at 21 degrees C, and two
      at 2 degrees C. Cyclosporine was extracted from samples taken on days 2, 4, 5, 7,
      9, 14, 18, 22, 28, and 31, and the concentration was measured by high-performance
      liquid chromatography (except for samples obtained on day 2) and fluorescence
      polarization immunoassay. Throughout the study period, the concentration of
      cyclosporine remaining in the paste was > 90% of the initial concentration
      according to both assay methods. Cyclosporine 9.6 mg/g in a paste compounded
      extemporaneously from cyclosporine oral solution and an adhesive gel was stable
      for at least 31 days when stored in aluminum-lined ointment tubes at 37, 21, and
      2 degrees C.

PMID- 8564592
TI  - Compatibility of amifostine with selected drugs during simulated Y-site
      administration.
AB  - The compatibility of amifostine for injection with selected other drugs during
      simulated Y-site injection was evaluated. Five-milliliter samples of amifostine
      10 mg/mL in 5% dextrose injection were combined with 5 mL each of 100 other
      drugs, including antineoplastics, anti-infectives, and supportive care drugs, in
      5% dextrose injection or 0.9% sodium chloride injection. The combinations were
      stored under fluorescent light at 23 degrees C. The combinations were evaluated
      initially and at one and four hours after preparation. Visual examinations were
      performed in fluorescent light with the unaided eye and using a high-intensity
      monodirectional light beam to enhance visualization of small particles and low
      level turbidity. The turbidity of each sample was measured. Particle sizing and
      counting were performed on selected samples. Most of the test drugs were
      compatible with amifostine 10 mg/mL for the observation period. However, 10 drugs
      exhibited various incompatibilities, including turbidity, particulate formation,
      precipitation, and color change. These drugs were acyclovir sodium, amphotericin
      B, cefoperazone sodium, chlorpromazine hydrochloride, cisplatin, ganciclovir
      sodium, hydroxyzine hydrochloride, miconazole, minocycline hydrochloride, and
      prochlorperazine edisylate. Amifostine 10 mg/mL in 5% dextrose injection was
      compatible with most of the 100 drugs tested for four hours at 23 degrees C.
      However, 10 drugs exhibited incompatibility with amifostine.

PMID- 8564593
TI  - Availability of lorazepam after simulated administration from glass and polyvinyl
      chloride containers.

PMID- 8564594
TI  - The third strategic-planning conference for pharmacy practice.

PMID- 8564595
TI  - Adverse reaction to rifampin mimicking symptoms of pulmonary tuberculosis.

PMID- 8564596
TI  - Incompatibility of amiodarone hydrochloride and sodium bicarbonate injections.

PMID- 8564597
TI  - Physician feedback on pharmacy-edited pharmacotherapy bulletin.

PMID- 8564598
TI  - FDA proposes easing research consent requirements in life-threatening situations.

PMID- 8564599
TI  - Treatment during primary HIV infection shows promise.

PMID- 8564600
TI  - New report validates needle-exchange programs. Programs slow spread of HIV
      without encouraging drug abuse.

PMID- 8564601
TI  - Federal-discount prices still off-limits to public hospitals.

PMID- 8564602
TI  - Medication-compliance recommendations target health professionals, industry
      groups, patients.

PMID- 8564603
TI  - Preparing for automated dispensing devices.

PMID- 8564604
TI  - Thinking about homeopathy.

PMID- 8564605
TI  - Cost of medication-related problems at a university hospital.
AB  - The cost to an institution of medication-related problems (MRPs) was studied. A
      retrospective chart review covering the period from July 1992 through June 1994
      was performed for patients at a university-affiliated medical center hospital who
      were known to have had clinical consequences from an adverse drug reaction (ADR)
      or medication error. All interventions resulting directly from the problem were
      recorded. A detailed list of patient charges was reviewed for each patient, and
      specific charges for the MRP-associated interventions were tabulated. The
      clinical outcomes used to evaluate intervention costs were categorized as extra
      laboratory tests, noninvasive procedures, additional treatments, invasive
      monitoring or procedures, increased length of stay, and intensive care. The cost
      of each intervention was calculated by applying the cost-to-charge ratio used in
      the institution's patient-charge-based accounting system. A total of 109 patient
      charts were reviewed. A total of 349 clinical outcomes associated with MRPs, or
      an average of 3 outcomes per patient, were detected. The mean +/- S.E. cost of
      MRP-associated clinical outcomes to the institution ranged from $95 +/- 11 for
      additional laboratory tests to $2640 +/- 596 for intensive care. The next most
      costly outcomes were increased length of stay and invasive monitoring or
      procedures. For the 1911 MRPs reported in 1994, the estimated total cost was
      almost $1.5 million. A review of the medical records of patients for whom an ADR
      or medication error had been recorded showed a high cost of these events to the
      institution, with the cost varying with clinical outcome, and a correspondingly
      strong opportunity for pharmacists to intervene to save money and improve the
      quality of care.

PMID- 8564606
TI  - Cost of providing pharmaceutical services to hospice patients.
AB  - The cost to a hospital pharmacy department of providing pharmaceutical services
      for a hospice program was studied. Drug acquisition costs were tabulated for all
      prescriptions dispensed to patients in the hospice program from April 1, 1992, to
      March 31, 1993. Direct time studies were conducted to determine the average
      personnel time involved in dispensing a prescription for a hospice patient. To
      determine the personnel time associated with auxiliary activities, self-reporting
      and work-sampling techniques were used. Indirect and delivery costs were also
      calculated. Relevant resource inputs were identified, measured, and valued by
      using both observation and pharmacy records. A total of 5640 hospice
      prescriptions were dispensed by the outpatient pharmacy; these represented 30% of
      all prescriptions dispensed. The average cost of dispensing a hospice
      prescription was $14.91 (total annual costs less drug acquisition costs). The
      total annual cost of providing pharmaceutical services to the hospice's patients
      was $196,607, and the total annual reimbursement received from the hospice
      program and self-paying patients was $155,623; therefore, costs exceeded revenues
      by $40,984. The cost to a pharmacy department of providing pharmaceutical
      services to patients in a hospice program substantially exceeded revenues.
      Greater efficiencies, a change in the pricing structure, or both may be
      necessary.

PMID- 8564607
TI  - Compatibility and activity of aldesleukin (recombinant interleukin-2) in presence
      of selected drugs during simulated Y-site administration: evaluation of three
      methods.
AB  - The compatibility and biological activity of aldesleukin (a form of recombinant
      interleukin-2) in the presence of selected i.v. drugs during simulated Y-site
      administration was studied. Five milliliters of aldesleukin 33,800 IU/mL in 5%
      dextrose injection was mixed in glass test tubes with 5 mL of each of 19 i.v.
      drugs prepared at concentrations used in routine clinical practice. The
      compatibility of the combinations was assessed by visual examination and
      spectrophotometry at 0, 0.5, 1, and 2 hours after preparation, and bioassays were
      conducted to determine the activity of aldesleukin in the combinations. Lorazepam
      was the only drug visually incompatible with aldesleukin. All the secondary drugs
      were spectrophotometrically compatible with aldesleukin. However, the bioassays
      showed that the following drugs reduced the activity of aldesleukin: ganciclovir
      sodium, lorazepam, pentamidine isethionate, prochlorperazine edisylate, and
      promethazine hydrochloride. Thus, aldesleukin became less biologically active
      when combined with four drugs for which visual examination suggested
      compatibility and when combined with five drugs for which spectrophotometry
      indicated compatibility. Aldesleukin 33,800 IU/mL in 5% dextrose injection lost
      significant biological activity in the presence of prochlorperazine edisylate,
      promethazine hydrochloride, lorazepam, ganciclovir sodium, and pentamidine
      isethionate during simulated Y-site administration. Visual assessment and
      spectrophotometry may not be valid methods for assessing possible changes in the
      biological activity of aldesleukin when combined with other agents.

PMID- 8564608
TI  - Stability of cefpirome sulfate in the presence of commonly used intensive care
      drugs during simulated Y-site injection.
AB  - The stability of cefpirome sulfate during simulated Y-site injection with drugs
      commonly used in the intensive care unit was studied. Cefpirome sulfate was
      constituted and diluted to 50 mg/mL with 0.9% sodium chloride injection, 0.45%
      sodium chloride injection, 5% dextrose injection, and lactated Ringer's
      injection. Each cefpirome sulfate solution was mixed 1:1 (simulating Y-site
      injection) with amikacin 5.0 mg/mL (as the sulfate salt), amphotericin B 0.1
      mg/mL, cefazolin 10 mg/mL (as the sodium salt), clindamycin 12.0 mg/mL (as the
      phosphate ester), dexamethasone phosphate 4.0 mg/mL (as the sodium salt),
      dopamine hydrochloride 0.8 mg/mL, epinephrine 0.1 mg/mL (as the hydrochloride
      salt), fluconazole 2.0 mg/mL, gentamicin 1.0 mg/mL (as the sulfate salt), and
      vancomycin 5.0 mg/mL (as the hydrochloride salt). All the drug combinations were
      prepared in triplicate and maintained at 23 degrees C. The combinations were
      observed visually at intervals up to eight hours, pH was measured, and samples
      were tested for drug concentration by high-performance liquid chromatography.
      Cefpirome was stable in the presence of each of the secondary drugs throughout
      the study period. All the secondary drugs except amphotericin B were stable in
      the presence of cefpirome. There were no visual phenomena indicating
      incompatibility. Changes in pH were minimal. Cefpirome 50 mg/mL (as the sulfate
      salt) in four different diluents was stable in the presence of each of 10
      commonly used intensive care drugs for at least eight hours during simulated Y
      site administration. Amphotericin B 0.1 mg/mL was not stable in the presence of
      cefpirome sulfate.

PMID- 8564609
TI  - Stability of ramipril in water, apple juice, and applesauce.
AB  - The stability of ramipril in water, in apple juice, and in applesauce was
      studied. The contents of a single capsule each of ramipril 1.25, 2.5, and 5 mg
      were mixed in glass beakers with 120 mL of deionized and filtered water, apple
      juice, or applesauce. Each mixture was apportioned into 10 120-mL amber
      polyethylene terephthalate (PET) containers. Five of the containers in each set
      were stored at 23 degrees C, and samples were taken at 0, 1, 2, 6, 12, and 24
      hours. The other five containers were stored at 3 degrees C, and samples were
      taken at 4, 8, 12, 24, and 48 hours. The samples were analyzed for ramipril
      concentration by stability-indicating high-performance liquid chromatography
      (HPLC). The quantity of drug remaining in the PET container after
      "administration" was determined by mixing the contents of single 5-mg ramipril
      capsules with 60 mL of apple juice, pouring the mixture into a waste receptacle,
      rinsing the PET container three separate times with 10 mL of water, and analyzing
      the pooled fluid from these rinses for ramipril concentration by HPLC. Under no
      condition did the percentage of ramipril remaining drop below 90%. No peaks for
      degradation products appeared in the chromatograms. The mean +/- S.D. quantity of
      ramipril remaining in the PET containers after draining was 0.3 +/- 0.3% for the
      apple juice. Ramipril from 1.25-, 2.5-, and 5-mg capsules mixed in water, in
      apple juice, and in applesauce was stable for 24 hours at 23 degrees C and for 48
      hours at 3 degrees C.

PMID- 8564610
TI  - Informing a patient about a homeopathic preparation.

PMID- 8564611
TI  - What pharmacists should understand about homeopathic remedies.

PMID- 8564612
TI  - Ensuring safety in the use of automated medication dispensing systems.

PMID- 8564613
TI  - The safety and hazards of blood-derived drugs.

PMID- 8564614
TI  - Criteria for use of atovaquone oral suspension in adult inpatients and
      outpatients.

PMID- 8564615
TI  - Home infusion of antimicrobials as an option for patients with AIDS.

PMID- 8564616
TI  - Ticarcillin-clavulanate as an alternative to imipenem-cilastatin.

PMID- 8564617
TI  - Drop size of ocular timolol solutions.

PMID- 8564618
TI  - Bacteriologic survey of a cleanroom.

PMID- 8564619
TI  - Comments on treatment of diabetic foot infections.

PMID- 8564620
TI  - Outlawing homeopathy in Israel.

PMID- 8564621
TI  - Predicting radon testing among university employees.
AB  - To determine covariates of radon testing behavior, we surveyed by mail a random
      sample of all Boston University employees (N = 915) six to nine months after they
      had been informed of the availability of radon testing services through the
      University's medical center. The response rate was 58%. Analysis suggests blue
      collar workers were underrepresented within the response rate. Slightly more than
      half of the respondents (51%) were men. The majority (69%) were under the age of
      45. Twenty-seven percent of the respondents (N = 143) had tested their homes for
      radon. Bivariate analysis revealed important differences between radon testers
      and nontesters. Testers were 12 times more likely to be home owners than renters
      (p = 0.00), and were more knowledgeable about radon's characteristics and testing
      procedures (p = 0.00). Testers were more likely to view radon as a serious
      problem (p = 0.00), to consider radon testing efficacious (p = 0.00), and to
      consider themselves susceptible to exposure (p = 0.00). Testers were also less
      likely to perceive barriers to radon testing. We used logistic regression to
      compare the usefulness of the Health Belief Model and the Diffusion of
      Innovations Model in predicting radon testing. We concluded that the knowledge
      deficits and barriers to radon testing identified in this study should be
      targeted in radon educational interventions.

PMID- 8564622
TI  - Clinical evaluation of asthma.
AB  - OBJECTIVE: The purpose of this article is to review the medical history and
      physical examination of the asthmatic patient. DATA SOURCES: English references
      identified from relevant articles and book chapters, experts, and MEDLINE search,
      using "asthma," "physical diagnosis," and "medical history." STUDY SELECTION:
      Clinical studies of the medical history or physical examination in subjects with
      respiratory disease were selected for review. RESULTS: Symptoms such as wheezing,
      chest tightness and difficulty in taking a deep breath suggest asthma, while
      symptoms such as gasping, smothering or air hunger suggest alternative diagnoses.
      Symptoms of asthma correlate poorly with airway obstruction in one-third to one
      half of asthmatic patients. Respiratory signs such as wheezing, breath sound
      intensity, forced expiratory time, accessory muscle use, respiratory rate and
      pulsus paradoxus correlate roughly with airway obstruction. However, clinicians
      disagree on the presence or absence of respiratory signs 55% to 89% of the time.
      Furthermore, physicians correctly predict pulmonary function based on history and
      physical examination only about half the time, and correctly diagnose asthma
      based on the clinical examination 63% to 74% of the time. CONCLUSIONS: The
      medical history and physical examination are moderately effective in diagnosing
      asthma and estimating its severity. Objective measures of lung function are
      necessary for the accurate diagnosis of asthma.

PMID- 8564623
TI  - Rash and fever in a 3-year-old girl.

PMID- 8564624
TI  - Asthma deaths in Washington State, 1980-1989: geographic and demographic
      distributions.
AB  - BACKGROUND: Asthma prevalence and mortality rates have been increasing for the
      past two decades for reasons that are not definitively known. Few studies of
      asthma mortality rates have concentrated on subnational regions, such as
      individual states. OBJECTIVE: To determine geographic and demographic patterns of
      asthma mortality in Washington State during 1980 through 1989 and to compare
      aggregated data with patterns of chronic bronchitis mortality. METHODS: Age
      adjusted mortality rates for asthma and chronic bronchitis were calculated from
      1980 through 1989 for all age groups. Rates were then disaggregated by county,
      gender, age, and race. Rates were calculated from death certificates listed by
      the Washington State Center for Health Statistics as either asthma (ICD9-493) or
      chronic bronchitis (ICD9-490 and 491) and census data. RESULTS: During the period
      1980-1989, age-adjusted mortality rates for asthma increased by 15% while those
      for bronchitis decreased by 43%. There was no consistent geographic pattern in
      the increase, though one county with a very small population had the highest rate
      of increase. Female asthma mortality rates increased during the decade, while
      male asthma mortality rates and both male and female bronchitis rates decreased.
      Two populations demonstrated pronounced increases in asthma mortality rates:
      females between ages 40 and 69 years and non-whites. CONCLUSIONS: While increased
      asthma mortality rates have been noted elsewhere for non-whites, this is the
      first study to demonstrate elevated mortality rates for middle aged women. The
      explanation for this remains a mystery.

PMID- 8564625
TI  - Efficacy and safety of inhaled bitolterol mesylate via metered-dose inhaler in
      children with asthma.
AB  - BACKGROUND: There have been numerous studies in asthmatic adults demonstrating
      the efficacy and safety of bitolterol mesylate metered-dose inhaler; however,
      only one additional study has examined bitolterol metered-dose inhaler in
      pediatric asthma. OBJECTIVE: To establish the safety and effectiveness of
      bitolterol mesylate metered-dose inhaler at one, two, and three inhalations in
      pediatric asthmatic patients 4 to 12 years of age. METHODS: A multicenter, double
      blind, randomized, crossover, placebo-controlled, dose-ranging study. Forty-six
      patients were evaluated in three centers. Patients were stratified by age, 4 to
      6, 7 to 9, 10 to 12 years at each center. One, two, or three inhalations were
      administered along with an additional double-blind, randomized, placebo dose.
      Bronchodilation was defined as a 15% or greater increase in FEV1 over baseline.
      Onset, maximum improvement, and duration of action were obtained for each
      patient. Serial pulse rate, blood pressure, and respiratory rate determinations
      were obtained for each patient. RESULTS: Onset within five minutes occurred in
      56.6% to 71% of patients, depending on the dose. Mean maximum improvement, which
      was dose dependent, overall ranged from 28.2% to 40.3% with a peak response in
      66.7 to 69.8 minutes. In direct relationship of magnitude with regard to dose of
      bitolterol was observed, (P < .001). A significant correlation, r = .732, in
      response between bronchodilation and baseline FEV1 was observed (P < .001).
      Median duration of action ranged from three to four hours in responding patients
      across all doses. Up to 31% of patients had durations greater than eight hours
      after three inhalations. Adverse effects were reported in five of 46 patients for
      all doses with mild transient tremor occurring in two patients, 4.3%. Also, there
      was little effect on pulse rate, 2.2%. CONCLUSION: Bitolterol is an effective
      bronchodilator with durations of activity up to eight hours and minimal adverse
      effects in children.

PMID- 8564626
TI  - Oral allergy syndrome induced by chestnut (Castanea sativa)
AB  - BACKGROUND: Oral allergy syndrome is a distinctive type of allergy to food
      resulting from direct contact between food and the oral mucosa. Normally, it
      affects patients who are allergic to pollens. It can be challenged by testing for
      hypersensitivity to fresh fruit or vegetables in well-known associations. Oral
      allergy syndrome rarely occurs in patients with other types of allergies, or to
      food not associated with pollens. Only occasionally does chestnut cause
      hypersensitivity. There are only a few reported cases, depending on cross
      reactivity in previously latex-hypersensitive patients. Oral allergy syndrome to
      chestnut in a patient with respiratory allergy to Dermatophagoides is therefore
      unusual and worth reporting. OBJECTIVES: To describe the clinical features and
      their differences from previously reported cases and to analyze the techniques
      and methodologic problems related to in vivo and in vitro diagnosis. METHODS:
      Case report. Skin tests with commercial and freshly made extracts and by the
      prick-by-prick method. Challenge test. Specific IgE antibody assay. Prausnitz
      Kustner reaction. RESULTS: The challenge with fresh food confirmed an oral
      allergy syndrome to chestnut. Clear symptoms of rhinoconjunctivitis and asthma
      set in as well. Skin tests with several commercial extracts and the prick-by
      prick test were negative and so was specific IgE assay in serum by RAST and other
      immunoenzymatic methods. Skin prick test with a freshly prepared extract of fresh
      chestnut and the passive transfer reaction were positive. CONCLUSIONS: The case
      of oral allergy syndrome to chestnut reported here appears to be a manifestation
      of immediate IgE-dependent hypersensitivity.

PMID- 8564627
TI  - Microflora and acarofauna of bed dust from homes in Upper Silesia, Poland.
AB  - BACKGROUND: Pyroglyphid mites are considered a major cause of house dust allergy.
      The occurrence and possible pathogenic role of other biologic components of house
      dust, in particular bacteria, has received less attention. OBJECTIVE: The aim of
      this study was to examine bacteria present in the samples of house dust from
      beds, in comparison to fungi and mites recovery. METHODS: Samples of bed dust
      were collected from 40 homes in Upper Silesia (Poland). Of these, 19 came from
      the homes of people with asthma caused by house dust and 21 from the homes of
      people without allergy. The concentrations of bacteria, fungi, mites, and
      endotoxin and species composition of microflora and acarofauna were determined.
      RESULTS: The overall mean concentrations of mesophilic bacteria, thermophilic
      bacteria and fungi, including yeasts, were, respectively, 1.6 x 10(6), 1.7 x
      10(3), and 1.6 x 10(4) CFU/g. Samples contained an average of 8.4 mites/g and the
      ten samples assayed for bacterial endotoxin averaged 80.4 ng/mg. A total of 55
      species of bacteria, 40 of fungi and 13 of mites were found. Gram-positive cocci
      (mostly Staphylococcus spp.) were the predominant mesophilic bacteria, followed
      by corynebacteria and Bacillus spp. Thermophilic bacteria were represented only
      by actinomycetes, with Thermoactinomyces vulgaris predominant. The most numerous
      fungi were Penicillium spp. and Aspergillus spp. followed by yeasts. The most
      abundant mites were Dermatophagoides spp. which formed > 85% of the total count.
      There were no significant differences between the homes of allergic and
      nonallergic people in the concentrations of total bacteria, fungi, and mites.
      Bacillus, Aspergillus and total filamentous fungi (molds), but not yeasts, were
      significantly more numerous in the homes of people with asthma caused by house
      dust. CONCLUSION: The results suggest that some species of bacteria and
      filamentous fungi should be considered potential causes of house dust allergy.

PMID- 8564628
TI  - Prevalence of latex-specific IgE antibodies in hospital personnel.
AB  - BACKGROUND: Rubber latex hypersensitivity is an important concern for health care
      workers. PURPOSE: The Center for Devices and Radiological Health, in
      collaboration with the Consumer Product Safety Commission, conducted a
      multicenter study of the prevalence of latex-specific IgE antibodies among United
      States hospital personnel. MATERIALS AND METHODS: Nine hospitals participated in
      the cross-sectional study. A total of 504 hospital personnel completed
      questionnaires that provided an array of demographic, occupational, and clinical
      information, including a history, if any, of allergies and the use of latex and
      nonlatex gloves. More than three-quarters (76.5%) of the participants were tested
      for total IgE and latex specific IgE. RESULTS: A total of 21 (5.5%, 95% CI = 3%
      7%) of the tested participants were positive for the presence of latex specific
      IgE antibodies, defined as a latex IgE level of > or = 0.6 ng/mL. Latex specific
      IgE antibodies were more prevalent in participants who reported tachycardia,
      palpitations, flushing, or wheezing associated with latex gloves (Odds Ratio =
      10.2, 95% CI = 3.7-28.6). CONCLUSION: The study's results suggest that the
      prevalence of latex-specific IgE antibodies among hospital personnel is
      appreciable and these personnel and their health care providers should be aware
      of this entity.

PMID- 8564630
TI  - Allergy to penicillin and cephalosporins.

PMID- 8564629
TI  - Efficacy and duration of salmeterol powder inhalation in protecting against
      exercise-induced bronchoconstriction.
AB  - BACKGROUND: The protective effect of a new long acting beta 2-agonist,
      salmeterol, against exercise-induced bronchoconstriction has been documented when
      given as inhaled aerosol. OBJECTIVE: The aim of the present study was to examine
      the duration of the protective effect of a single dose of salmeterol, 50
      micrograms, inhaled as dry powder, against exercise-induced bronchoconstriction.
      METHODS: Sixteen patients with reproducible exercise-induced bronchoconstriction
      were challenged on a treadmill on two prestudy visits and six study days. The
      patients were challenged 4, 8, and 12 hours postdosing. The study was designed as
      a double blind placebo-controlled randomized crossover trial. RESULTS:
      Statistically significant differences in % maximum fall in PEFR were found at
      four and eight hours postdosing, in favor of salmeterol. At 12 hours postdosing,
      no clear statistical inference was possible, owing to the presence of a
      statistical carry-over effect; however, significant differences in area under
      curve in favor of salmeterol were found at 4, 8, and 12 hours postdosing.
      CONCLUSION: Salmeterol, 50 micrograms, dry powder inhalation had a protective
      effect against exercise-induced bronchoconstriction up to 12 hours postdosing, as
      compared with placebo. No adverse effects were identified.

PMID- 8564631
TI  - Intraocular pressure after a two-week washout following long-term timolol or
      levobunolol.
AB  - The effect on intraocular pressure (IOP) of a 2-week washout following long-term
      ocular therapy with topical levobunolol or timolol for an average period of 30
      months was investigated in 20 patients (11 whites and 9 blacks) with early
      primary open-angle glaucoma or ocular hypertensive glaucoma suspect status. The 2
      week washout IOP was significantly lower than the pretreatment baseline IOP in
      the total 20 patients (P < 0.001), and in the 9 black patients (P = 0.004), but
      not in the 11 white patients (P = 0.065). However, the washout IOP was found to
      be significantly lower than the baseline IOP in the 5 whites with brown irides (P
      = 0.024) but not in the 6 whites with blue irides (P = 0.574). Thus, the 2-week
      washout following long-term ocular therapy with a topical beta 1-, beta 2-blocker
      appears insufficient to restore IOP to the pretreatment baseline level in blacks
      and in the whites with brown irides, whereas it may be adequate in the majority
      of the whites with blue irides.

PMID- 8564632
TI  - The use of trabeculectomy to study the pharmacological modulation of ophthalmic
      wound healing.
AB  - A trabeculectomy model was developed to test the efficacy of a putative
      interleukin-1 blocker on the modulation of ophthalmic wound healing in the
      pigmented rabbit. The corticosteroid, methylprednisolone acetate, was used as a
      positive control and was effective in prolonging the time to failure of the
      trabeculectomy. The experimental compound CK-103A was found to be more
      efficacious than methyl prednisolone acetate. CK-103A increased the time of
      failure by 79%, with no side effects at the doses tested to date.

PMID- 8564633
TI  - Effects of interleukin-1 blockers on ophthalmic wound healing in a rabbit model
      of trabeculectomy.
AB  - A trabeculectomy model was used to test the efficacy of some Interleukin-1
      blockers on the modulation of ophthalmic wound healing in the pigmented rabbit.
      The corticosteroid, methyl prednisolone, was used as a positive control and was
      effective in prolonging the time to failure of the trabeculectomy by 21%. The
      experimental compounds CK-17, CK-101A, CK-102 and CK-103A were more efficacious
      than vehicle control at prolonging the number of days before failure of the
      trabeculectomy by 55%, 55%, 30% and 79%, respectively. The CK- compounds
      increased the amount of time before failure of the fistula, with no side effects
      at the doses tested to date.

PMID- 8564634
TI  - Endothelins inhibit cyclic AMP production in rabbit and human ciliary processes.
AB  - The effects of endothelins on cyclic AMP production have been studied in rabbit
      and human ciliary processes. Endothelins inhibit basal, isoproterenol-, and VIP
      stimulated cyclic AMP production in rabbit ciliary processes and forskolin
      stimulated cyclic AMP production in rabbit and human ciliary processes. EC50s for
      inhibition of forskolin-stimulated cyclic AMP production using rabbit tissue were
      similar: ET-1, 70 nM; ET-2, 40 nM; ET-3, 70 nM; maximum inhibition was about 76%
      for each ligand. These data are consistent with the presence of an ETB receptor.
      Endothelin-like immunoreactivity in rabbit aqueous humor was measured to be 226
      pg/ml.

PMID- 8564635
TI  - Topically applied hydralazine: effects on systemic cardiovascular parameters,
      blood-aqueous barrier, and aqueous humor dynamics in normotensive humans.
AB  - Local application of hydralazine has been found to alter intraocular pressure in
      animal eyes. This study was undertaken to determine, in normotensive humans, the
      effects of topically-applied hydralazine on systemic cardiovascular parameters,
      blood-aqueous barrier, and aqueous humor flow. Two different concentrations of
      hydralazine were used: 0.03%, and 0.1%. Twenty healthy normotensive subjects were
      studied. Blood pressure, pulse rate, and intraocular pressure were measured every
      hour for six hours after hydralazine or placebo was instilled into the
      conjunctival sac in a double-masked, randomized fashion. With either hydralazine
      dose, there was no significant change in systemic blood pressure or pulse. In
      addition, spectrophotometrically-measured polarization of fluorescence and flare
      failed to show any significant breakdown of the blood-aqueous barrier. In most
      individuals, application of hydralazine was followed by a brief, mild to
      moderate, conjunctival hyperemic response. Compared to placebo at the same time
      of day, a small increase in intraocular pressure was observed with 0.03%
      hydralazine (p < .05). At 0.1%, this increase tended to be less. There was no
      statistically significant difference in aqueous humor flow between hydralazine
      treated and placebo-treated eyes at the lower concentration (3.20 +/- 0.63 vs.
      3.05 +/- 0.61 microL/min (mean +/- S.D.) or at the higher concentration (3.37 +/-
      0.53 vs. 3.28 +/- 0.60 microL/min) of hydralazine. These results suggest that
      acute topical application of 0.1% hydralazine to the eyes of normal humans does
      not cause clinically significant cardiovascular effects or significant ocular
      toxicity.

PMID- 8564636
TI  - Trapidil inhibits endothelial cell proliferation and angiogenesis in the chick
      chorioallantoic membrane and in the rat cornea.
AB  - The effects of trapidil, a coronaro-active drug which has been shown to inhibit
      the mitogenic activity of platelet derived growth factor (PDGF), have been
      investigated on the proliferation of the human endothelial cells (HUV-EC-C), on
      the neovascularization in the chorioallantoic membrane of the chick embryo (CAM)
      as well as on the angiogenesis of rat cornea following chemical injury. The
      proliferation of HUV-EC-C in the presence of trapidil (25 and 250 micrograms/mL)
      was significantly inhibited by 19 and 25% respectively, compared to controls. On
      2-days old CAMs, agarose disks containing 100-150 micrograms of trapidil produced
      an avascular zone indicating significant antiangiogenic activity, while control
      agarose disks were without effect. Corneal neovascularization was induced by
      applying a silver nitrate/potassium nitrate applicator to the rat eyes. A 6-day
      treatment with eye drops of a solution of 10 mg/mL trapidil significantly
      decreased the rate of vessel growth compared with vehicle controls. The
      antiangiogenic activity of trapidil was markedly increased by the association
      with hydrocortisone (1.34 mg/mL). These results suggest that trapidil, alone or
      in combination with a steroid, could be a promising candidate for the therapy of
      corneal diseases in which alterations induced by neovascular growth play a
      substantial role.

PMID- 8564637
TI  - Histamine actions in dog retinal central arteries as compared to those in middle
      cerebral and temporal arteries.
AB  - PURPOSE: Mechanisms underlying the relaxant response to histamine were compared
      in isolated dog retinal arteries (branch of internal and external carotid
      arteries), middle cerebral arteries (branch of internal carotid artery) and
      superficial temporal arteries (branch of external carotid artery). METHODS:
      Changes in the isometric tension of helical strips of the arteries with and
      without the endothelium were recorded. RESULTS: Histamine produced concentration
      related biphasic (phasic and sustained) relaxations in retinal arterial strips
      contracted partially with prostaglandin (PG)F2 alpha. Relaxations induced by
      histamine were not dependent on the endothelium. Treatment with cimetidine
      attenuated the sustained relaxation, whereas chlorpheniramine or indomethacin
      depressed the phasic relaxation. In addition, the phasic relaxant response to
      histamine was attenuated by tranylcypromine, a PGI2 synthesis inhibitor. In
      contrast, the amine-induced relaxant responses in dog middle cerebral arterial
      branch and temporal arteries were markedly suppressed by cimetidine alone.
      CONCLUSIONS: In dog retinal arteries, the phasic relaxation caused by histamine
      is mediated by PGI2 in association with activation of the H1 receptor subtype in
      subendothelial tissues, possibly smooth muscle, and the sustained relaxation is
      evoked by direct stimulation of the H2 receptor subtype in smooth muscle. The
      histamine-induced relaxation in temporal and distal middle cerebral arteries is
      associated solely with a stimulation of H2 receptors in smooth muscle.

PMID- 8564638
TI  - Side effects of rapamycin in the rat.
AB  - The side effects of Rapamycin was evaluated by histopathological examination of
      the heart, kidneys, and eyes of treated Lewis rats. Rapamycin was administered
      during 14 days by continuous intravenous infusions at doses of 0.5, 1.0, and 1.5
      mg/kg/day. Focal myocardial infarction was observed in three of five rats with
      Rapamycin given at 1.5 mg/kg/day and two of 22 rats with 1.0 mg/kg/day. There
      were no sign of myocardial toxicity at a Rapamycin dose of 0.5 mg/kg/day. The
      retina of one eye of a rat treated at a dose of 1.5 mg/kg/day had a small area of
      focal ischemic necrosis. The kidneys were normal at all doses.

PMID- 8564639
TI  - Ocular toxicity of iontophoretic foscarnet in rabbits.
AB  - Transscleral iontophoresis of foscarnet is a noninvasive drug delivery system for
      the local treatment of cytomegalovirus (CMV) retinopathy. We determined the
      retinotoxic effects of transscleral iontophoresis of foscarnet. Slit-lamp
      biomicroscopy revealed no toxic effects for any of the treated eyes. Indirect
      ophthalmoscopy showed retinal and choroidal burns 1-3 mm in diameter at the site
      of iontophoresis in both foscarnet-treated eyes and saline-treated control eyes.
      Light and electron microscopy revealed focal retinal, retinal pigment epithelial,
      and choroidal necrosis at the site of iontophoresis but no abnormalities
      elsewhere. Ganzfeld electroretinographic studies revealed no response differences
      between foscarnet-treated eyes vs. controls.

PMID- 8564640
TI  - Sulfobutyl ether beta-cyclodextrin (SBE-beta-CD) in eyedrops improves the
      tolerability of a topically applied pilocarpine prodrug in rabbits.
AB  - The effects of a novel, modified beta-cyclodextrin (SBE4-beta-CD; a variably
      substituted sulfobutyl ether with an average degree of substitution of four) on
      eye irritation and miotic response of an ophthalmically applied pilocarpine
      prodrug, O,O'-dipropionyl-(1,4-xylylene) bispilocarpate, in albino rabbits were
      studied. Compared to the commercial pilocarpine eyedrop solution (163 mM,
      equivalent to 3.4% pilocarpine), 12-24 mM pilocarpine prodrug solutions
      (equivalent to 0.5-1.0% pilocarpine, respectively) decreased peak miotic
      intensity (Imax) and increased the time to reach peak (tmax), but did not
      significantly affect values for the area under the miosis versus time curves
      (AUC), i.e. 12-24 mM pilocarpine prodrug appeared to be equivalent to 163 mM
      pilocarpine. Ocularly applied 12-24 mM pilocarpine prodrug solutions, however,
      were more irritating than a commercial pilocarpine eyedrop solution.
      Coadministered SBE4-beta-CD significantly decreased the eye irritation of the
      pilocarpine prodrug solutions. Coadministered SBE4-beta-CD did not affect the
      miotic response of prodrug solution when the molar ratio of SBE4-beta-CD to
      prodrug was low. However, increasing the molar ratio of SBE4-beta-CD to prodrug
      decreased the Imax and AUC values. The results show that eye irritation of the
      pilocarpine prodrug is prevented by levels of SBE4-beta-CD that do not affect the
      apparent ocular absorption of the prodrug.

PMID- 8564641
TI  - Interest and limits of human tissue and cell use in pharmacotoxicology.

PMID- 8564642
TI  - Acquisition and use of human in vitro liver preparations.
AB  - Human in vitro liver preparations-i.e., slices, hepatocyte suspensions, primary
      hepatocyte cultures and microsomes-are increasingly used in the drug development
      process. The main applications are prediction of drug metabolite profiles, drug
      drug interactions and toxicity. The use of these in vitro models is limited,
      however, because of their erratic availability, the absence of validated
      protocols and the difficulties of extrapolation of in vitro data to the in vivo
      situation.

PMID- 8564643
TI  - Relationships between in vitro and in vivo biotransformation of drugs in humans
      and animals: pharmaco-toxicological consequences.
AB  - Given the crucial role played by hepatocytes in the detoxification/toxification
      processes of drugs, these cells have been increasingly used during the last
      decade in various pharmaco-toxicological areas. The majority of these studies
      have, however, dealt with animal cells, although examples of failures in the
      extrapolation of the data to man are frequent. This drawback, together with the
      ethical considerations in performing in vivo experiments, makes the application
      of the human hepatocyte model critical in the preclinical evaluation of new
      compounds. However, before making extensive use of these promising tools for
      prospective pharmaceutical research, one must ensure that they can generate data
      that correlate well with those obtained in vivo. This is only possible through
      extensive studies on drugs showing a variety of phase I and phase II metabolic
      pathways in hepatocytes from different species, including man, and comparison
      with in vivo data. Providing this validation step is undertaken, the use of such
      systems in drug research and development may greatly enhance the rational design
      of safe and effective drugs, allowing savings in time, cost and test materials as
      well as minimizing the use of animals.

PMID- 8564644
TI  - Primary dissociated cultures of human brainstem cells: a useful tool for their
      characterization and neuroprotection study.
AB  - Dissociated cell cultures were prepared from brainstems of 5- to 10-week-old
      human fetuses. Catecholamine- as well as indolamine-containing cells were
      visualized using respectively dopamine (DA), noradrenaline (NA) and serotonin
      (5HT) as immunocytochemical markers. NA-, DA-, and 5HT-stained cells were
      characterized in the rhombencephalic cultures, representing respectively the
      fetal localization of the locus coeruleus and raphe nuclei. DA-stained cells were
      characterized in the mesencephalic cultures; these DA-cells originating from the
      substantia nigra presented morphological aspects different from the DA
      rhombencephalic cells. Two types of GABA neurons and glial cells presenting glial
      fibrillary acidic protein (GFA-P) reactivity were also found in all the cultures.
      Two non-competitive N-methyl-D-aspartate antagonists, 1-[1-(2
      thienyl)cyclohexyl]piperidine (TCP) and cis-Pip/Me 1-[1-(2-thienyl)-2
      methylcyclohexyl]piperidine (GK11) in enantiomeric form (-), have been
      investigated for survival on rhombencephalic cultured cells. The number of 5HT
      cells was found to be greater in the treated cultures than in the control ones.
      This in vitro system appears to be a useful tool for the investigation of the
      development of central nervous system (CNS) cells as well as the study of
      neuroprotection.

PMID- 8564645
TI  - Cell stress and implications of the heat-shock response in skin.
AB  - Heat-shock proteins (HSPs), or so-called 'stress proteins' may play an important
      role in cutaneous pathophysiology. HSPs are a group of highly conserved molecules
      that are expressed by all cells when subjected to heat or other forms of physical
      or chemical stress. The physiological roles of stress proteins are varied and are
      important in stress and nonstress conditions. They bind to other cellular
      proteins and participate in protein folding pathways during stress and also
      during the synthesis of new polypeptides. HSPs are also essential for
      thermotolerance and for prevention and repair of damage caused in DNA after
      ultraviolet exposure. Although HSPs are expressed in the skin in both epidermis
      and dermis, HSPs may influence many other cellular processes in the inflammatory
      and immune skin response. Many authors have speculated on a link between HSPs and
      human skin disease characterized by inflammation and proliferation.

PMID- 8564646
TI  - Pharmacotoxicological applications of an equivalent dermis: three measurements of
      cytotoxicity.
AB  - The legal procedure for evaluating the toxicity of cosmetic, household, chemical
      and pharmaceutical products is still the irritancy Draize test on rabbits.
      Various irritation tests are currently being developed as alternatives to in vivo
      animal testing. Our in vitro model system is composed of 24 equivalent dermis
      (ED) comprising a chitosan-cross-linked collagen-glycosaminoglycan matrix
      populated by foreskin fibroblasts. In evaluating this system for irritancy
      testing, three different measures of toxicity were used: MTT (dimethylthiazol
      diphenyltetrazolium bromide) reduction, and lactate dehydrogenase and interleukin
      6 release. The experiments described herein represent a preliminary evaluation to
      determine the usefulness and predictive value of our 24 ED kit as an alternative
      method for the prediction of human dermal reaction, versus three chemical
      products: cadmium chloride, lauryl sulfate, and benzalkonium chloride.
      Preliminary results suggest that the ED may be a useful in vitro model for the
      prediction of cutaneous and ocular toxicity and allow the development of a 24
      skin-equivalent kit realized by seeding human normal keratinocytes onto the
      equivalent dermis.

PMID- 8564647
TI  - Clinical interest of cutaneous models reproduced in vitro for severe burn
      treatment: histopathological and ultrastructural study.
AB  - The healing of minimal skin lesions is usually obtained by epidermal migration
      and proliferation from peripheral wound margins. However, cutaneous grafts or
      reconstituted skin are necessary for severe injuries. Various models have
      recently been reproduced for this purpose. The aim of this work is to report the
      histopathologic evolution of burn lesions treated two years ago by autologous
      epidermis (Genzyme Tissue Repair, Boston, USA). Fifteen patients with severe
      burns (more than 80% of surface) have been treated. These observations have been
      based exclusively on biopsies of grafted wounds. Cultured epidermis is rapidly
      fully differentiated after grafting with temporary hyperplasia and normal strata.
      At 18 months, rete ridges formation is present only in young patients.
      Melanocytes and Langerhans' cells repopulated grafts rapidly. The use of cultured
      epidermis nowadays represents an important improvement in burn treatment.

PMID- 8564648
TI  - Human cell lines in pharmacotoxicology. An introduction to a panel discussion.
AB  - Various types of cells lines are used in pharmacotoxicology. Established cell
      lines are easily available, with few ethical restrictions. Some specific
      properties are preserved, although they have kept the phenotype of the original
      tissue, which is frequently a tumor phenotype. They are usually more resistant to
      toxic compounds than freshly isolated cells. Some drug-metabolizing enzymes are
      expressed and regulated in these cells. Immortalized cell lines are also of
      interest in toxicology. They are mainly examined for their potential in
      mutagenicity testing. These cells and numerous others of animal or human origin
      can be transfected with cDNA coding for human enzymes. They are used for
      determination of the individual enzyme involved in a particular metabolic
      pathway, or, when multiple transfections are successfully achieved, for
      mutagenicity testing. Regulation studies are also possible in such cells after
      transfection of DNA elements regulating gene transcription.

PMID- 8564650
TI  - [Antagonist or antidote?].

PMID- 8564649
TI  - The human intestinal epithelial cell line Caco-2; pharmacological and
      pharmacokinetic applications.
AB  - The gastrointestinal tract remains the most popular and acceptable route of
      administration for drugs. It offers the great advantage of convenience and many
      compounds are well absorbed and thereby provide acceptable plasma concentration
      time profiles. Currently there is considerable interest from the pharmaceutical
      industry in development of cell culture systems that would mimic the intestinal
      mucosa in order to evaluate strategies for investigating and/or enhancing drug
      absorption. The intestinal epithelial cells of primary interest, from the
      standpoint of drug absorption and metabolism, are the villus cells, which are
      fully differentiated cells. An in vitro cell culture system consisting of a
      monolayer of viable, polarized and fully differentiated villus cells, similar to
      that found in the small intestine, would be a valuable tool in the study of drug
      and nutrient transport and metabolism. The Caco-2 cell line, which exhibits a
      well-differentiated brush border on the apical surface and tight junctions, and
      expresses typical small-intestinal microvillus hydrolases and nutrient
      transporters, has proven to be the most popular in vitro model (a) to rapidly
      assess the cellular permeability of potential drug candidates, (b) to elucidate
      pathways of drug transport (e.g., passive versus carrier mediated), (c) to assess
      formulation strategies designed to enhance membrane permeability, (d) to
      determine the optimal physicochemical characteristics for passive diffusion of
      drugs, and (e) to assess potential toxic effects of drug candidates or
      formulation components on this biological barrier. Since differentiated Caco-2
      cells express various cytochrome P450 isoforms and phase II enzymes such as UDP
      glucuronosyltransferases, sulfotransferases and glutathione-S-transferases, this
      model could also allow the study of presystemic drug metabolism.

PMID- 8564651
TI  - [Natriuresis and atrial natriuretic factors during extracorporeal circulation for
      cardiac surgery].
AB  - At the end of cardiopulmonary bypass (CPB) diuresis and natriuresis are widely
      modified. Those are classically due to the CPB conditions (mean arterial
      pressure, non pulsatile flow, hypothermia, long duration ...). Previous studies
      showed no evidence of these modifications being due to variations of hormones
      such as vasopressin, renin or aldosterone. The atrial natriuretic factor, cardiac
      hormone mainly known for its natriuretic effect, would contribute to explain
      these facts. This study includes 17 patients NYHA I or II without any renal
      dysfunction or diabetes mellitus. They were scheduled for cardiac surgery under
      CPB (valvular replacement or aortocoronary bypass). Sampling times were: TO:
      after induction of anaesthesia and before surgical incision; T1: during steady
      CPB; T2: 30 min after CPB release. At each time were obtained: diuresis, osmolar
      and free water clearance, fractional excretion of sodium, haematocrit, plasma
      concentration of ANF (pANF), and right atrial pressure and capillar wedge
      pressure in case of aortocoronary graft. FeNa at the end of CPB is significantly
      linked to the osmolar clearance and the CPB duration. FeNa evolution is parallel
      with pFAN evolution. At the end of CPB pFAN is first linked to cardiac rate, then
      to CPB duration. Cardiac filling pressures after and before CPB are not
      different. pANF after CPB cannot be attributed to these pressures. Numerous
      factors are involved in the renal sodium elimination. An evident statistic link
      between pANF and FeNa is then difficult to demonstrate. Their parallel evolution
      is coherent and suggests that ANF is the main hormone of natriuresis at the end
      of CPB. ANF secretion factors at the end of CPB remain unclear. This study
      emphasizes the involvement of cardiac rate and CPB duration in pANF increase at
      the end of CPB.

PMID- 8564652
TI  - [Efficacy of propacetamol in postoperative pain based on two modes of intravenous
      administration].
AB  - The analgesic and antipyretic efficacy of propacetamol is identical to
      paracetamol. Because the propacetamol is injectable and its side effects are
      uncommon and mild, it is the drug commonly used in France for postoperative pain
      relief. The aim of this prospective study was to compare the analgesic efficacy
      of propacetamol after breast surgery or thyroidectomy when it was administered
      either systematically or on the patients demand. After informed consent, 119
      patients having undergone breast surgery or thyroidectomy, having received the
      same general anaesthesia and scheduled for receiving propacetamol
      postoperatively, were included in the study. Two groups of patients were
      compared, those who received propacetamol on demand (D Group) and those who
      received propacetamol systematically (S Group). During the first 24 hours,
      analgesia was evaluated on a visual analogical scale graded from 0 to 100 mm, at
      rest and during mobilization; the efficacy was also evaluated by the amount of
      additional analgesic drug injected. Side effects were also compared between the 2
      treatment groups. In the 2 groups, demographic data, type of anaesthesia and type
      of surgery were identical. Postoperative pain relief and supplemental injection
      of morphine were not statistically different between the 2 groups. Propacetamol
      doses were statistically higher in the S group than in the D group (7.8 +/- 0.7 g
      and 3.9 +/- 2.3 g respectively, p < 0.05). Pain during propacetamol infusion was
      more frequent in the D group than in the S group (30% and 13% respectively, p <
      0.05). No other adverse effects were observed during the study. Propacetamol
      alone is sufficient for pain relief after peripheral surgery; more than 90% of
      patients need no supplemental analgesic, and adverse effects are rare.

PMID- 8564653
TI  - [Antidepressive agents, the dorsal horn and pain].

PMID- 8564654
TI  - [Interactions between opioids and local anesthetics at the level of the dorsal
      horn of the spinal cord].
AB  - For many years, local anaesthetic drugs, given spinally, have been used to
      control pain after surgery or during parturition. For nearly 20 years, we have
      known that opioids given by the same way have an analgesic effect. However the
      later group do not provide satisfactory analgesia in several pain contexts but
      also give troublesome side effects; local anaesthetics are associated also with
      side effects. Experimental and clinical studies have shown that the combination
      of local anaesthetics with opioids provides some degree of synergism, associated
      with a reduction of side effects. Further studies are needed to confirm the
      analgesic benefit and the potential decrease of side effects, but also to
      determine the minimal effective dose regimen in relation with the type of pain.

PMID- 8564656
TI  - [Plasma exchange and severe Plasmodium falciparum malaria. Apropos of 2 cases].
AB  - Severe Falciparum malaria is associated with multiple organ dysfunction and a
      high rate of fatal outcome. Appropriate antimalarial chemotherapy and symptomatic
      treatment may be supplemented by early plasma exchange. Two cases are reported in
      which there were no chemoprophylaxis and a late diagnosis. Initial parasitaemias
      were 17% and 5%. The two patients had cerebral malaria with in the first case
      pulmonary oedema and DIC. Plasma exchange was performed and clinical biological
      symptoms abated quickly. The mechanisms of action and benefits of plasma exchange
      are discussed.

PMID- 8564655
TI  - [Effects of preoxygenation methods on the course of PaO2 and PaCO2 in anesthetic
      post-induction apnea].
AB  - This study compares two preoxygenation techniques by blood gases measurements
      during induction of anaesthesia. After hospital ethics committee approval, 17
      adult surgical patients, ASA I, all free of cardiac or lung disease were randomly
      assigned to two groups. Before preoxygenation, venous and radial artery
      canulations were performed. The patients were not premedicated and rested supine.
      Oxygen was given using a Mapleson A system with a 10 l.min-1 flow. In group I, 9
      patients breathed 100 per cent O2 with a normal pattern. In group II, 8 patients
      took four deep breaths of 100 per cent O2 within 30 seconds. After this, the mask
      was removed and anaesthesia was induced with thiopental (5 mg.kg-1),
      phenoperidine (0.04 mg.kg-1) and vecuronium (0.1 mg.kg-1). After intubation,
      patients remained apnoeic until SpO2 decreased to 90%. Samples for arterial blood
      gas measurements were obtained before preoxygenation and then every minute. The
      two groups were similar in age (26.8 +/- 8.1 vs 29.2 +/- 9.0 years) and weight.
      The group I had significantly higher PaO2 immediately after preoxygenation (397
      +/- 49 vs 293 +/- 86 mmHg) and the time for SaO2 to decrease to 95% was
      significantly shorter in group II (3 +/- 1 vs 1.87 +/- 0.99 min). PaCO2 was not
      different after preoxygenation in group II. In summary, healthy and young
      patients receive better protection against hypoxia with normal breathing of 100%
      for 4 minutes.

PMID- 8564657
TI  - [Severe interstitial and mediastinal emphysema caused by petroleum poisoning].

PMID- 8564658
TI  - [Duplication of the vena cava].
AB  - Bilateral superior vena cava is a congenital anomaly of which the
      anaesthesiologist and intensivist should be aware in order to not mistake
      catheters placed in the left superior vena cava as being malpositioned outside of
      the venous circulation. These malpositions generally require catheter removal and
      reinsertion. This anomaly although rare is not-so-unusual. It is generally well
      tolerated.

PMID- 8564659
TI  - [Improving tissue perfusion without invasive monitoring. Apropos of a case].
AB  - A case is reported of a 64 year old patient who suffered a septic shock after
      surgical treatment of a biliary peritonitis. Increasing myocardial contractility
      and aortic blood flow by dobutamine appeared ineffective; added norepinephrine
      infusion improved the peripheral perfusion. This clinical improvement in tissue
      perfusion was evaluated by non-invasive continuous monitoring of the haemodynamic
      profile, combining aortic blood flow measurement by a transoesophageal echo
      Doppler and continuous measurement of end-tidal carbon dioxide.

PMID- 8564660
TI  - [Shoshin beriberi. Apropos of a fatal case].

PMID- 8564661
TI  - [Laryngeal masks in emergency medicine].
AB  - Airway control and maintenance of effective assisted ventilation are an absolute
      priority in emergency medicine. Developed by Brain in 1988, the laryngeal mask
      offers a new means of ventilation management and is a reliable compromise between
      the face mask and endotracheal tubing. The laryngeal mask ensures no protection
      against gastric contents inhalation and its use is limited in patients with
      decreased thoracopulmonary compliance. However, compared to the face mask, the
      laryngeal mask offers several benefits in the management of cardiorespiratory
      arrests by paramedical staff and rescue teams: the procedure is easy to learn,
      the device improves airway patency, leaves the operator's hands free, allows
      endotracheal aspiration to be performed and reduces the risk of
      hyperinsufflation. These advantages make the use of the laryngeal mask a
      technique which should be taught to any staff liable to face and manage cases of
      cardiorespiratory arrest. The laryngeal mask cannot and does not replace
      endotracheal tubing which remains the only technique that guarantees upper airway
      patency and protection as well as efficient ventilation control. However, in some
      situations tubing may prove difficult and even, at times, impossible to perform.
      This is when the laryngeal mask will come in handy, either as a temporary
      solution or as an alternative to difficult or impossible tubing techniques.

PMID- 8564662
TI  - [The life of John Snow. Abridged translation of the biography by Benjamin W.
      Richardson].

PMID- 8564663
TI  - [Report on the prehospital management of emergencies].

PMID- 8564664
TI  - [Salvaging of drained blood in orthopedic surgery].

PMID- 8564665
TI  - [A study of blood loss during surgery for scoliosis. Posterior approach in 319
      adolescents].
AB  - A retrospective study including 319 patients was realized from 1984 to 1993 in
      order to evaluate during scoliosis surgery the incidence on bleeding of the type
      of scoliosis and the anesthetic procedure. Blood losses were below one litre thus
      reducing the homologous blood transfusions. The patient was in prone position on
      a modified Wilson frame which facilitates venous return from the dorsal region. A
      moderate controlled hypotension was realized by combination of halothane,
      intravenous nitroglycerin (NG) and beta-blocking drugs (when required).
      Somatosensory evoked potentials were continuously monitored during surgery. A
      compression of the dorsal region was realized postoperatively in order to reduce
      blood loss. The blood losses were compared using Student's t-test. The mean
      perioperative bleeding was 9.8 ml.kg-1 for idiopathic scoliosis (no transfusion
      required), 14.1 ml.kg-1 for secondary scoliosis (p < 0.05 vs idiopathic) and 29.3
      ml.kg-1 for neuromyopathic scoliosis (p < 0.05 vs idiopathic), indicating a major
      influence of muscle atonia on bleeding. The moderate controlled hypotension by
      iterative injection of NG and beta-adrenergic blocking drugs provided a safe and
      reversible hypotension.

PMID- 8564666
TI  - [Influence of droperidol on the hypnotic effect of thiopental].
AB  - We studied the effect of DBP on thiopentone hypnosis in 580 patients aged 20 to
      30 and 560 patients aged 40 to 50. The hypnotic effect of thiopentone was
      evaluated after 5, 15, 30, 45 and 60 minutes from intravenous administration of
      0.05 mg.kg-1 of DBP by using dose-effect curves to identify the ED50 dose. The
      ED50 value of thiopentone decreased up to 15 minutes after DBP (about 1.1 mg.kg-1
      in both age groups) and increased after 30, 45 and 60 minutes, the increase being
      higher in the patients aged 40 to 50. We concluded that DBP has a synergic effect
      with thiopentone and the pharmacokinetic and alpha 1-lytic effects of DBP are
      responsible of an increased need of barbituric in the patients aged 40 to 50.

PMID- 8564667
TI  - [Neurologic manifestations of fat embolism].
AB  - Neurologic manifestations are usual and variable during post-traumatic fat
      embolism. The pathogenesis of these lesions continues to be a source of
      considerable controversy. Thirteen cases of post-traumatic fat embolism with
      neurologic signs were treated in a surgical intensive care unit. All patients had
      impaired consciousness. Focal neurologic disorders were reported in 5 cases
      [hemiplegia (2), tetraplegia (2), aphasia (1)]. The aspects on brain CT scan
      seemed to be related to ischemic lesions (1 case), appeared normal in ten cases,
      or revealed post-traumatic hemorrhagic lesions (2 cases). The outcome at 2-4
      weeks was spontaneously good, with complete resolution, without neurologic
      sequellae, in 11/13 patients. Two deaths were related to brain trauma severity
      (one case) and nosocomial pneumonia (one case).

PMID- 8564668
TI  - [Psychiatric management of multiple trauma].
AB  - In resuscitation or surgery departments, the recourse to the psychiatrist
      regarding a polytraumatized patient occurs according to two main contexts.
      Firstly, patients with major psychiatric troubles are concerned, sometimes after
      suicide attempts. Secondly, patients with behaviour disorders or somatic
      complaints may attract the physician's attention. The authors study the
      psychiatric intervention in those various cases.

PMID- 8564669
TI  - [Are atrial natriuretic factor, renin, aldosterone and catecholamines modified
      during general anesthesia for total hip arthroplasty?].

PMID- 8564670
TI  - [Management of neurologic manifestations after obstetrical epidural anesthesia].
AB  - Epidural anaesthesia is commonly used in obstetrics (70% of all deliveries in the
      maternity units of Lille University Hospital). Four cases are reported: headache
      followed by diplopia and amaurosis, delayed lumbosacral paraesthesia, early
      paraesthesia of the left lower limb, severe cephalalgia. Etiological analysis
      allowed to find the causes of these disorders and to exclude any anaesthesia
      responsibility, moreover permitting adapted treatments. The medicolegal aspect
      must be emphasized and also the need of an extensive medical investigation to
      find out the aetiology and propose an appropriate management.

PMID- 8564671
TI  - [Cerebral malaria in children in Cameroon. Apropos of 11 cases].
AB  - Eleven cases of cerebral malaria were observed among 106 hospitalized malarian
      children. A brief recall of pathophysiology is given, including its immunological
      aspect. Symptomatology and course of this severe form are evoked. All children
      were treated by IV then oral quinine and recovered without any neurological
      sequelae. The importance of a very early treatment is strongly emphasized.

PMID- 8564672
TI  - [Latex hypersensitivity: a foreseeable accident?].
AB  - This paper describes another case of severe anaphylactic reaction due to allergy
      to natural rubber during anaesthesia in a child without known risk factors. The
      day after surgery the child reported that he experienced a few months ago an
      impressive skin reaction of both face and lips after inflating a latex balloon.
      It is suggested to try to detect latex allergy during the preoperative visit in
      all patients by including questions about latex sensitivity such as previous skin
      reactions or respiratory symptoms after wearing latex gloves or after inflating
      toy balloons. Patients in whom latex sensitivity is suspected should be tested
      appropriately in order to perform the planned surgery in a latex-free
      environment.

PMID- 8564673
TI  - [Epidural anesthesia and esophageal atresia. Apropos of a case].
AB  - We report the good results of a thoracic epidural analgesia for oesophageal
      atresia repair in a 3-day old girl. Surgery was performed under light general
      anaesthesia combined with a single epidural injection of bupivacaine 0.25% (0.5
      ml.kg-1) with epinephrine through a 19 G catheter (T7 space, descending to T5).
      During the three following days, a continuous epidural infusion was used (0.2
      ml.kg-1.h-1 bupivacaine 0.125%). Intraoperative analgesia and postoperative
      analgesia were adequate, the latter being assessed by the Barrier-Amiel-Tison
      pain scale. Thus heavy postoperative care could be avoided, namely mechanical
      ventilation. Recovery was uneventful.

PMID- 8564674
TI  - [Factor VII deficiency and surgery: is preoperative replacement necessary?].

PMID- 8564675
TI  - [Peritonitis caused by minor intestinal perforation during subacute brucellosis.
      Apropos of a case].

PMID- 8564676
TI  - [Traumatic emergencies and hemostasis].
AB  - The occurrence of bleeding in trauma patients is a life-threatening problem which
      can be explained by different mechanisms. The infusion of cristalloids, colloids,
      packed red blood cells, or even fresh frozen plasma is very rarely responsible
      for bleeding but it can contribute to dilute the patient's platelet pool, and
      especially dilutional thrombocytopenia is the first cause of bleeding after
      massive transfusion. Blood coagulation factor activity is decreased after a
      massive fluid infusion is performed but it has to reach a dramatically low plasma
      level in order to induce troubles. It has to be emphasized that colloids and
      especially dextrans can impair the patient's haemostasis by interfering the same
      way with the factor VIII-von Willebrand complex and fibrin formation. Gelatins do
      not interfere with platelets or with the coagulation system. A third mechanism
      that can explain the strong link between haemostasis and haemodilution is the
      haemostatic role of red cells. It has been shown in experimental models that red
      cells play a definite function in promoting platelet accretion on the damaged
      vessel surface. Higher values of haematocrit (Ht) are responsible for a better
      platelet adhesion On the opposite, platelet adhesion decreases when low values of
      Ht (< 20%) are reached. Hypothermia can also impair platelet function and worsen
      the bleeding. A simplified monitoring of haemostasis can be proposed with
      platelet count, whole blood coagulation clotting time, immediately available
      activated partial thromboplastin time and prothrombin time with bedside portable
      monitors and thromboelastography. Haematocrit and body temperature have to be
      monitored as well.

PMID- 8564677
TI  - [Lung contusion in the multiple trauma patient].
AB  - The main management's characteristics of the pulmonary contusion in the trauma
      patients are explained. From possible alveolocapillary membrane's injuries, with
      consideration of worsening evolution (ARDS, nosocomial infection, MOF), main
      points of discussion are circulation and mechanical ventilation. For the most
      severely injured, invasive monitoring is necessary, including the oxygenation
      parameters we now can dispose of. Quantification of extravascular lung water is
      an original and valuable tool to determine the time course and amount of
      pulmonary oedema. There is no ideal mode of ventilation but the basic ventilatory
      patterns must be adjusted; a target is the reduction of time requirement for
      ventilatory support.

PMID- 8564678
TI  - [Hemorrhagic complications of ORL surgery].

PMID- 8564679
TI  - [Midazolam versus placebo before spinal anesthesia].
AB  - The goal of this randomized, double blind and multicentric study was to compare
      the effects of midazolam (M) and placebo (P) administered by titration before
      puncture for spinal anaesthesia on the comfort of 211 patients scheduled for
      elective surgery after oral premedication with hydroxyzine. The administered dose
      of midazolam was 3.4 +/- 1.3 mg (mean +/- SD). Anxiety was nil in 92% of the
      patients of the M group and in 64% of the patients of the P group (p < 0.001) and
      memorization of the pain of the puncture was reported in 34% of the patients of
      the M group and in 66% of the patients of the P group (p < 0.001). However
      cooperation of the patient and easiness of the puncture were similar in both
      groups. In conclusion titrated sedation with midazolam before puncture for spinal
      anaesthesia increases the comfort of the patient.

PMID- 8564680
TI  - [The laryngeal mask in ophthalmologic surgery. Criteria and limitations of use in
      adults (analysis of 57 cases)].
AB  - Clinical and physical data about laryngeal mask use in eye surgery were collected
      in 57 patients. We observed 4 failures which required endotracheal intubation, 3
      leaks during operative field installation, 4 salvations but no laryngeal spasm
      and no cough. There were no significative differences between body weights in
      laryngeal mask groups no 3 and no 4. Insufflation pressures of patients without
      curarisation were more important. The duration of ventilation was not correlated
      with salivation, leaks or increase of insufflation pressure.

PMID- 8564681
TI  - [Peri-bulbar anesthesia for cataract surgery].
AB  - Ninety-five peribulbar blocks for cataract extraction with intraocular lens
      implantation were performed by an anaesthetist over a period of 6 months. The
      quality of the block was assessed by the ophthalmologist and the anaesthetist. No
      dangerous local or systemic complications were observed. Peribulbar anaesthesia
      is increasingly preferred to retrobulbar block on account of its easiness and
      safety.

PMID- 8564682
TI  - [Scientific anesthesiology of John Snow].

PMID- 8564683
TI  - MR imaging techniques for soft-tissue lesions.
AB  - MR imaging is the technique of choice for detection, characterization, and
      staging of soft-tissue neoplasms. MR examinations need to be tailored to each
      patient based upon the patient's size and anatomic region of interest so that
      optimal information is obtained. Technique is critical. Proper positioning to
      allow patient comfort and reduce motion artifacts is essential. Selection of the
      appropriate coils, image planes, and optimal pulse sequences to identify and
      determine the extent of lesions is critical for therapy planning.

PMID- 8564684
TI  - Surgical considerations in a diagnostic imaging evaluation of musculoskeletal
      masses.
AB  - The management of patients with soft-tissue masses necessitates careful
      assessment and appropriate use of investigational tools to obtain a diagnosis.
      The interaction among surgeons, radiologists, and pathologists allows adequate
      staging of soft-tissue tumors and better planning of the definitive treatment.
      The ability of MR imaging to maximize contrast between normal and tumor tissues
      in any desired plane makes it usually the best cross-sectional imaging modality
      in the preoperative staging of soft-tissue masses.

PMID- 8564685
TI  - MR imaging versus alternative imaging techniques.
AB  - MR imaging is the method of choice in evaluating a large number of soft-tissue
      abnormalities; however, it has certain draw-backs, some of which may make other
      imaging methods more suitable. MR imaging is more expensive than alternative
      imaging methods; it may not be affordable for screening purposes and for
      diagnoses obtainable by less expensive imaging methods. In addition, immediate
      scheduling is not always possible for MR imaging, and an MR scanner may not be
      available close to the patient's home, which may be important for imaging follow
      up. These factors support the use of other imaging modalities, with sonography
      frequently being the appropriate choice. In some situations, mainly in the
      presence of certain biomedical implants and devices, MR imaging is
      contraindicated. Additionally, under some circumstances patient access may be
      difficult during MR imaging; sonography and CT therefore are preferable (as for
      imaging guided biopsy). Moreover, some artifacts, such as motion artifacts, may
      have less relevance in other imaging methods (such as sonography), which may be
      important in noncooperative patients and children. MR imaging may not be specific
      in tumors and infection; this deficiency is shared with most alternative imaging
      methods, with the exception of scintigraphy in selected indications. Lastly,
      standard radiography and CT commonly are superior to MR imaging in diagnosing
      calcification and abnormalities of cortical bone. Consequently, in selected cases
      and for screening purposes, methods other than MR imaging should be considered
      for depicting soft-tissue structures.

PMID- 8564686
TI  - MR imaging of benign soft-tissue masses.
AB  - Benign masses outnumber sarcomas. The use of MR imaging for the indeterminate
      soft-tissue mass has during the past decade permitted radiologists to name the
      soft-tissue mass or provide a succinct differential diagnosis. This article
      reviews the identification of benign masses based on signal intensity, location,
      morphologic characteristics, and other features. The importance of approaching
      every "indeterminate" mass after MR imaging as malignant until proved otherwise
      is emphasized, as is the fact that despite the accessibility of the mass, a
      biopsy should not be done without prior consultation with an orthopedic
      oncologist.

PMID- 8564687
TI  - MR imaging of malignant soft-tissue tumors.
AB  - Nearly 6000 cases of soft-tissue sarcoma are diagnosed annually. Many are
      evaluated with MR imaging, which, because of its superior tissue contrast, has
      become the most important tool for detecting, staging, and monitoring treatment
      of the primary tumor. Although irregular margins, invasion of bone, and vascular
      encasement are indicators of soft-tissue malignancy, sarcomas may also be
      localized and well-circumscribed. Regardless of their histology, most soft-tissue
      sarcomas are similar in intensity to muscle on T1-weighted images and
      intermediate to high signal relative to fat on T2-weighted images. The addition
      of paramagnetic contrast agents can help differentiate between recurrent primary
      tumor and postoperative fluid collections.

PMID- 8564688
TI  - MR imaging of periarticular soft-tissue lesions.
AB  - The exquisite soft-tissue contrast and multi-planar imaging capabilities of MR
      imaging uniquely qualify this modality for the evaluation of periarticular
      pathology. MR evaluation can be diagnostic by signal characterization, as in a
      lipoma, or by anatomic location, as seen in meniscal and synovial cysts. In other
      less diagnostic pathology, MR imaging can focus a differential diagnosis, guide
      percutaneous or surgical biopsy, provide local staging, and serve as a surgical
      map.

PMID- 8564689
TI  - Benign and malignant masses. MR imaging differentiation.
AB  - Not only is MR imaging maximally sensitive to the presence of musculoskeletal
      soft-tissue lesions, but also it provides exquisite definition of their features.
      Categorization of the many distinct attributes of the lesions is the key to
      differentiation of benign from malignant processes. Combining the observations
      concerning the architectural details with the location and pattern of growth, and
      finally with the specific MR signal characteristics and contrast enhancement
      patterns, will produce the most limited differential diagnosis possible. Although
      there are few, if any, pathognomonic findings for malignant or benign lesions in
      diagnostic imaging, a high degree of confidence or statistical likelihood can be
      achieved in many instances using MR imaging.

PMID- 8564690
TI  - Soft-tissue sarcoma of the extremities. MR appearance of post-treatment changes
      and local recurrences.
AB  - MR imaging has the potential to provide valuable insights into intratumoral
      changes following preoperative therapy and has proven beneficial in the diagnosis
      of recurrent soft-tissue sarcoma of the extremities and differentiation of
      recurrence from postsurgical/postradiation changes. As advances occur in surgical
      and adjuvant treatment programs, further refinements of qualitative and
      quantitative MR imaging parameters should continue to enhance the role of MR
      imaging in the post-treatment evaluation of patients with soft-tissue sarcoma of
      the extremities.

PMID- 8564691
TI  - MR spectroscopy of musculoskeletal soft-tissue tumors.
AB  - Published studies of sarcomas using 31P MRS suffer from technical limitations
      that include absence of localization to regions of interest, resulting in heavy
      contamination with signals from muscle, and poor resolution. This review has
      shown that, in spite of their limitations, many of these studies provide
      important leads to indicate the directions that need to be taken to further
      develop clinical and biologic uses of MRS. The uniqueness of the metabolic
      information available in vivo in a noninvasive manner using MRS provides a major
      stimulus to pursue these directions. In particular, the potential of 31P MRS to
      predict treatment sensitivity and resistance in individual cases could lead to a
      very cost-beneficial clinical use of this procedure. 1H-decoupling and NOE
      enhancement, implemented in conjunction with dual-tuned surface coils and
      accurate localization of 31P MR spectra to regions of interest in three
      dimensions using CSI, have enabled us to overcome the major technical limitations
      mentioned earlier, broaden the scope of 31P MRS investigations, and obtain more
      information about the in vivo metabolic characteristics of soft-tissue sarcomas
      than has heretofore been available. Our approach, which has been fully
      implemented in a clinical imager, provides a good technical basis from which to
      examine potential clinical uses of 31P MRS. In particular, we can now rigorously
      test the hypotheses, derived from preliminary studies in the literature, that
      initial metabolic features or early treatment-induced changes in PME predict
      sensitivity of a sarcoma to that particular treatment. To this end, we at Fox
      Chase Cancer Center, along with investigators at Duke University, the Institute
      of Cancer Research/Royal Marsden Hospital, Johns Hopkins University, Memorial
      Sloan-Kettering Cancer Center, St. Georges Hospital Medical School, the
      University of California at San Francisco, and Wayne State University have
      initiated an NCI-sponsored cooperative trial to examine the role of 31P MRS in
      the clinical management of soft-tissue sarcomas and other selected cancers.

PMID- 8564692
TI  - MR imaging of soft-tissue masses. Mass-like lesions that simulate neoplasms.
AB  - The MR appearance of soft-tissue masses that simulate neoplasms has been
      described. In some cases, radiographs may demonstrate characteristic findings in
      association with MR imaging that may be diagnostic, such as an ossific rim seen
      in myositis ossificans, periosteal reaction seen in fibro-osseous pseudotumor,
      and retained foreign bodies present in a foreign body reaction or abscess. In
      other cases, the characteristic lesion location, age of the patient, and clinical
      presentation may be suggestive of the diagnosis, as in elastofibroma and nodular
      fasciitis.

PMID- 8564693
TI  - MR imaging of soft-tissue infection.
AB  - MR imaging is the ideal technique to display the soft-tissue abnormalities
      produced by infectious processes. In general these soft-tissue alterations
      consist of signal intensity changes that reflect the increased water content of
      the soft tissues induced by the inflammatory reactions. In some cases these
      changes are nonspecific, but in others, MR imaging can be quite specific and
      helpful in detecting the presence and extent of the infection, which generally is
      suspected clinically on the basis of physical and laboratory findings. The MR
      manifestations of soft-tissue infection, including septic arthritis,
      tenosynovitis, bursitis, cellulitis, necrotizing fascitis, soft-tissue abscess,
      infectious myositis, HIV-related infection, lymphadenitis and lymphangitis, and a
      few unusual parasitic and fungal infections, are reviewed.

PMID- 8564694
TI  - Musculotendinous injury.
AB  - Over the past decade, MR imaging has become one of the most valuable imaging
      tools for evaluation of musculoskeletal pathology. This is due to its high
      sensitivity to the vast majority of acute and chronic musculoskeletal injuries
      and the starting anatomic clarity provided. The latter feature allows definition
      of characteristic injury patterns, which is the key to most diagnoses and also
      usually allows accurate grading of the severity of injuries. Careful attention to
      imaging technique and the specific architectural patterns of musculotendinous
      disruption by the imaging specialist will result in accurate diagnoses for the
      patient and referring physician.

PMID- 8564695
TI  - Muscle weakness and myalgia. MR imaging investigation.
AB  - The status of muscle integrity need no longer be surmised on the basis of gross
      clinical assessments of muscle strength and invasive procedures. MR imaging
      brings to the clinical arena new capabilities to aid the management of patients
      with common muscle complaints of common and uncommon causes. Although findings on
      MR imaging tend to be nonspecific, muscle structural lesions can be defined in
      terms of extent and gross composition, and thus help direct invasive procedures
      and monitor therapies. Radiologists need to remember that their observation of
      muscle lesions on MR imaging may be the serendipitous discovery of the true cause
      of a patient's compliant.

PMID- 8564697
TI  - [Studies on colonic mucus release--II. Damaged colon mucosa].
AB  - The release of goblet cell mucus (GCM) was examined in immune reaction-system of
      colonic mucosa of rats (SD rats). We previously reported that in the immune
      reaction of normal colon of rats, the discharge of colonic GCM was not increased
      by intrarectal instillation (challenge) of several test-antigens after repeated
      immunization of single BSA antigen through rectal mucosa, and there was
      difference in local antigen-antibody reaction on the surface of normal mucosa
      between small intestine and colon. In the present study we investigated the
      release of colonic GCM in local antigen-antibody system in rats of damaged colon
      mucosa, who had repeated immunization of BSA after damage induction by
      intracolonic infusion of formalin. Consequently, the discharge of colonic GCM
      increased associated with local antigen-antibody reaction in animals after damage
      induction by formalin. It is suggested that when the mucosal barrier is
      disrupted, enhanced release of colonic GCM is occurred by the local immune
      reaction on the surface of colonic mucosa.

PMID- 8564696
TI  - [Facilitation of hepatic metastasis by surgical stress in mice].
AB  - An experimental model for hepatic metastasis with a transplantation route of free
      pedicled subcutaneous-embedded spleen was established in BALB/c mice. Colon-26
      tumor cells to produce hepatic metastasis were inoculated into the spleen and the
      influence of surgical stress by means of a 20-min exposure of the abdominal
      cavity on the incidence of hepatic metastasis was examined. Hepatic metastasis
      was more promoted by the surgical stress in order when it was given on the same
      day, the 7th day and the 3rd day of the inoculation. Administration, without
      surgical stress, of ASGM 1, a specific inhibitor of the natural killer activity,
      also facilitated the hepatic disease. Administration of OK-432 prior to the
      surgical stress or ASGM 1 was at least partly effective for prevention of the
      hepatic metastasis and prolonged the survival of the inoculated mice.
      Preoperative immunotherapy utilizing OK-432 might be a possible means to prevent
      hepatic metastasis triggered in colorectal surgery for cancer.

PMID- 8564698
TI  - [Effect of IL-10 on the mite antigen-induced IFN-gamma production by peripheral
      blood lymphocytes from individuals with bronchial asthma].
AB  - Interferon-gamma (IFN-gamma) production was dose-dependently suppressed by the
      addition of Dermatophagoides farinae (Df), mite antigen in peripheral blood
      mononuclear cells from children with bronchial asthma. By contrast, the levels of
      IFN-gamma did not change on stimulation with Df antigen in the normal lymphocytes
      from nonallergic individuals not sensitized with mite. Recombinant interleukin 10
      (IL-10), when added to the normal lymphocytes, significantly reduced the
      production of IFN-gamma. Moreover, the decreased synthesis of IFN-gamma in
      patients' lymphocytes was inversely up-regulated by the treatment with anti-IL-10
      antibody. Taken together, results suggest the regulatory role of IL-10 in the
      secretion of IFN-gamma in Df antigen-driven immune responses.

PMID- 8564699
TI  - [Identification and analysis of immune cells infiltrating into the glomerulus and
      interstitium in lupus nephritis].
AB  - This study was performed to investigate the role of cell-mediated immunity in
      lupus nephritis (LN). Frozen sections from 38 patients with LN were examined by
      indirect immunoalkaline-phosphatase labeling using monoclonal antibodies to
      identify the immune cells infiltrating into the interstitium and glomerulus. 14
      patients showed minor glomerular abnormality (MGA), 9 had mesangial LN (MesLN),
      12 had diffuse proliferative LN (DPLN) and 3 had membranous LN (MLN).
      Monocyte/macrophage and helper/inducer T cells infiltrated in the interstitium
      predominantly, but intraglomerular infiltration of these cells was rare.
      Monocyte/macrophage and suppressor/cytotoxic T cell levels were significantly
      higher (p < 0.05) in the interstitium in DPLN patients and monocyte/macrophage
      level was significantly higher (p < 0.05) in MesLN patients than in MGA patients.
      In the interstitium, serum creatinine level was highly correlated with
      infiltrations of suppressor/cytotoxic T cell, monocyte/macrophage (p < 0.01), pan
      T cell and total leucocyte (p < 0.05). Clinical activity score was correlated
      with suppressor/cytotoxic T cell (p < 0.001), monocyte/macrophage and pan T cell
      (p < 0.01). These results suggest that suppressor/cytotoxic T cell and and
      monocyte/macrophage may play an important role in the progression of lupus
      nephritis.

PMID- 8564700
TI  - [An autopsy case of dermatomyositis with rapidly progressive interstitial
      pneumonia].
AB  - An autopsy case of dermatomyositis with rapidly progressive interstitial
      pneumonia is reported. a 48-year-old woman was admitted because of facial
      edematous erythema and muscular weakness. A diagnosis of dermatomyositis was made
      because of typical erythema and myogenic pattern of EMG, although serum creatine
      kinase was within normal range. The chest X-ray film showed that interstitial
      pneumonia was complicated. She was treated with prednisolone of 60 mg/day.
      Although erythema and althralgia was improved remarkably, interstitial pneumonia
      was progressed unfavorably. Therefore pulse therapy with methylprednisolone was
      administered twice, but failed to respond. After that interstitial pneumonia was
      progressed rapidly, she was died of respiratory failure. The autopsy findings
      detected that a degeneration and necrosis of striated muscular fibers in whole
      body, that a mixed findings of usual interstitial pneumonia and diffuse alveolar
      damage in the lung. Vasculitis and fiblinous pleuritis was also found in the
      lung. Malignancy was not detected.

PMID- 8564701
TI  - [Undifferentiated connective tissue syndromes (UCTS) accompanied by laryngeal
      involvement and autoimmune hepatitis].
AB  - Here we report a patient with undifferentiated connective tissue syndromes (UCTS)
      who developed hoarseness during exacerbation of autoimmune hepatitis. A 51-year
      old woman was hospitalized in November 1993 because of hoarseness and liver
      dysfunction. She had demonstrated Raynaud's phenomenon, polyarthralgia and
      hoarseness since 1992. In August 1993, liver dysfunction was noted. On admission,
      laboratory data showed mild leukopenia, thrombocytopenia (WBC 3,900/mm3, platelet
      12.4 x 10(4)/mm3), and elevations of transaminase (GOT 96 IU/l, GPT 79 IU/l) and
      IgG (4,556 mg/dl). Anti-nuclear antibody (ANA) and anti-smooth muscle antibody
      were positive. Other autoantibodies including anti-DNA antibody, anti-Scl 70
      antibody were all negative. LE test and LE cells were also negative. On
      laryngoscopic examination, lesions that appeared similar to a bamboo-joint were
      noted at the middle of the bilateral vocal cords. Pathological findings of liver
      biopsy specimen were compatible with autoimmune hepatitis. She was treated with
      30 mg of prednisolone. Polyarthralgia, hoarseness and the abnormalities of the
      transaminase levels improved rapidly. Laryngoscopic findings were also
      normalized. We considered this laryngeal involvement to be acute laryngitis
      accompanied by some UCTS, including a typical systemic lupus erythematosus (SLE)
      because of arthritis, cytopenia and ANA positivity. Involvement of the larynx in
      collagen disease is rarely mentioned in published reports.

PMID- 8564702
TI  - [A case of sarcoidosis with renal failure as the main manifestation in
      granulomatous interstitial nephritis].
AB  - A 39-year-old woman was consulted to our hospital because of renal failure on
      October 1992. A chest X-ray showed no abnormal shadow. Subsequently, she was
      under conservative treatment until December 1993, when she began to notice
      clouded vision. The iridocyclitis in both eyes was diagnosed by a
      ophthalmologist. She was admitted to our hospital for the purpose of a renal
      biopsy. Laboratory tests revealed renal failure: a creatinine clearance of 24.5
      ml/min, a serum level of creatinine of 3.2 mg/ml and blood urea nitrogen of 38.7
      mg/dl. The angiotensin converting enzyme was 17.6 IU/ml (normal 8.3 approximately
      21.4 IU/ml), but lysozyme was 49.5 micrograms/ml (normal 5.0 approximately 10.2).
      Mantoux's reaction was negative. 57Ga scintigram showed abnormal uptakes on eyes,
      bilateral salivary gland, both thighs, both kidneys, and in a part of lung field.
      A percutaneous renal biopsy revealed non-caseating histiocytic granulomas with
      diffuse infiltration of lymphocytes and neutrophils into interstitium. Glomeruli
      were ischemic and mild endocapillary proliferations with pericapsular fibrosis
      were seen. Both of transbronchial lung biopsy (TBLB) and skin biopsy also
      revealed non-caseating histiocytic granulomas. Oral administration of
      prednisolone, 40 mg/day, improved the level of serum creatinine and lysozyme.
      Sarcoidosis is a granulomatous disease of unknown etiology that may involve any
      organ or tissue of the body. The clinical picture dominating in adults is the one
      with pulmonary and mediastinal lymph node involvement, eye and skin lesions.
      Although the renal involvement were rarely encountered, the present case showed
      that the renal failure was one of the most important clinical feature in patient
      with sarcoidosis.

PMID- 8564703
TI  - Roles of stem cell factor in the in vitro growth of blast clonogenic cells from
      patients with acute myeloblastic leukemia.
AB  - We investigated the effects of stem cell factor (SCF) on the growth of blast
      clonogenic cells from 27 patients with acute myeloblastic leukemia (AML) and 3
      patients with chronic myelocytic leukemia in myeloid crisis. SCF alone showed a
      significant stimulatory activity in 15 of 30 patients (50%). A marked reduction
      in the number of blast cell colonies supported by SCF alone was noted by the
      addition of neutralizing antibody (Ab) against granulocyte-macrophage colony
      stimulating factor (GM-CSF). Ab against interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha) also moderately reduced the number of colonies, whereas
      Ab against granulocyte CSF (G-CSF) failed to do so. All four Ab together
      completely abolished the growth in 5 of 6 patients tested. c-kit antisense
      oligonucleotides reduced the colony formation supported by IL-3 or G-CSF or, in
      the absence of growth factor, in only 2 of 10 patients tested. SCF caused
      stimulation by acting synergistically with G-CSF, GM-CSF, IL-3, IL-6, IL-9, IL
      11, and IL-12 in 20 of 27 (74%), 17 of 27 (63%), 14 of 28 (50%), 9 of 28 (32%), 1
      of 15 (7%), 3 of 28 (11%), and 2 of 15 (13%) patients, respectively. Thus, SCF
      alone or in combination with some other factor stimulated the growth in 27 of 30
      (90%) patients. Of 3 nonresponders, 2 were AML, M3 at presentation. G-CSF at the
      optimal concentration increased the sensitivity of blasts to SCF. Taken together,
      SCF acting in combination with other factors, but not alone, stimulates the
      growth of blast clonogenic cells. GM-CSF, IL-6, and TNF-alpha may be produced
      endogenously, whereas G-CSF and SCF may be supplied exogenously. Autocrine
      regulation of the growth of blasts seems to increase the responsiveness of the
      cells to any of these factors, allowing them to achieve a highly active growth
      state.

PMID- 8564704
TI  - Effective treatment with interferon-alpha in chronic recurrent multifocal
      osteomyelitis.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is a rare disease of unknown
      etiology characterized by multiple osteomyelitic changes in the predominantly
      metaphysial regions of long bones. It was first described by Giedon et al. in
      1972. Cultures for all known microorganisms are negative. Pain is the most common
      symptom, and sometimes soft tissue swelling is present. Patients are usually
      treated with nonsteroidal antiinflammatory drugs (NSAIDs) or corticosteroids and
      respond, at least partly, to these treatments. CRMO is most commonly seen in
      children and is in the majority of cases self-limiting but has a protracted
      course of several years. Some patients have a more prolonged disease period, as
      in the patient reported here. Treatment with corticosteroids in children has the
      risk of causing growth retardation as a potential adverse effect, and alternative
      treatments are of great interest. In the actual paper, a successful treatment
      with interferon-alpha 2b in a 34-year-old man with CRMO is presented.

PMID- 8564705
TI  - Regression of human breast cancer xenografts in response to intralesional
      treatment with interferons alpha and gamma potentiated by tumor necrosis factor.
AB  - The potentiating effects of human recombinant tumor necrosis factor-alpha (rTNF
      alpha) on the antitumor actions of recombinant interferon-gamma (rIFN-gamma) and
      of natural interferons alpha and gamma combined (nIFN-alpha/nIFN-gamma) were
      studied on human breast cancer xenografts growing bilaterally in nude mice. The
      cytokines were injected singly or in combination in one of the two tumors of each
      mouse to study local effects while the opposite tumor was left undisturbed to
      evaluate systemic effects. The tumors received 20 intralesional injections (four
      cycles of 5 daily injections each). In injected tumors the best results were
      obtained with nIFN-alpha/nIFN-gamma supplemented with rTNF-alpha. The responses
      were dose dependent, resulting in complete regression of 9 of 9 tumors with rTNF
      alpha used at the dose of 5 micrograms per injection, of 6 of 8 tumors at the
      dose of 2.5 micrograms, and of 4 of 8 tumors at the dose of 0.5 microgram. Mostly
      mild to moderate partial responses were seen in the other groups. The systemic
      effects on the contralateral tumors were significantly less than the local
      effects on the corresponding tumors. Histologically, responding tumors showed
      reactive fibrosis and inflammatory cell infiltration. No vascular alterations
      were seen, presumably because of the immunodeficiency of nude mice. It was
      concluded that the potentiation of the antitumor actions of IFNs by rTNF-alpha
      was effective at the local but not at the systemic level.

PMID- 8564706
TI  - Inhibition of human immunodeficiency virus type 1 multiplication by transforming
      growth factor beta 1 and AZT in HIV-1-infected myeloid cells.
AB  - Myeloid cells are important reservoirs of HIV-1 infection. In response to
      pathogenic agents, macrophages secrete inflammatory cytokines that can modulate
      viral replication and contribute to AIDS pathogenesis. Because HIV replication is
      dependent on cellular activation, immunosuppressive cytokines that deactivate
      macrophages and T cells may be important modulators of an antiviral effect. We
      tested the anti-HIV potential of the immunosuppressive cytokine-transforming
      growth factor beta (TGF-beta 1) alone and in combination with AZT in a new
      monomyeloblastic model of HIV-1 infection. The PLB-985 cell model was infected
      with HIV IIIB strain, and the course of HIV-1 infection and replication was
      monitored by reverse transcriptase assay, p24 immunofluorescence, and northern
      blot analysis of HIV-1-specific mRNA. TGF-beta 1 as a single agent had no effect
      on the multiplication of HIV-IIIB in de novo-infected PLB 985 monomyeloblastic
      cells. However, cotreatment with TGF-beta 1 and AZT synergistically slowed virus
      multiplication within the first week following infection, as determined by
      reverse transcriptase measurement, p24 antigen detection, and northern blot
      analysis of viral RNA. The synergistic actions of TGF-beta 1 and AZT were also
      observed in PLB 985 cells infected with an AZT-resistant strain of HIV-1 (HIV
      1393). Synergism between nucleoside analogs and cytokines may be an important
      therapeutic approach to HIV-1 infection. Elucidation of the role of cytokines in
      controlling the degree of HIV multiplication may have an impact on both clinical
      treatments and understanding the progression to AIDS.

PMID- 8564707
TI  - Activity of the interferon-induced 2',5'-oligoadenylate synthetase in patients
      with chronic hepatitis C.
AB  - The interferon-induced 2',5'-oligoadenylate synthetase (2-5OAS) is responsible,
      at least in part, for the antiviral state established in cells in response to
      viral infections. The purpose of this work was to study the relationship between
      hepatitis C virus (HCV) infection and 2-5OAS in patients with chronic hepatitis
      C. Peripheral blood mononuclear cells (PBMC) of 27 patients with chronic
      hepatitis C were investigated, as well as PBMC of 10 control subjects. Then, the
      patients were treated with 3 mu interferon-alpha 2a three times per week. At
      month 3 of therapy, PBMC were sampled. Of the total PBMC samples obtained, half
      were used for determination of in vivo 2-5OAS activity. The remaining cells were
      cultured for 24 h in either the absence or presence of 500 U/ml of interferon
      alpha 2a for the determination of in vitro 2-5OAS activity. The mean basal in
      vivo 2-5OAS activities were 3.6 +/- 2.8 nmol/10(6) cells in patients versus 1.6
      +/- 1.1 nmol/10(6) cells in controls (p < 0.01). Basal in vivo 2-5OAS activity
      did not correlate with mean HCV viremia, quantified by a "branched DNA"-based
      assay. Before treatment, interferon-alpha was detected in the serum of 2 patients
      in 27. After a 24 h culture of PBMC in the presence of interferon, in vitro 2
      5OAS activity was significantly induced in the PBMC of both the patients and the
      controls. However, in vitro induction of 2-5OAS activity was significantly lower
      in the PBMC of the patients than in the PBMC of the controls (p < 0.01). At month
      3 therapy, in vivo 2-5OAS activity was significantly induced (20.5 +/- 17.9; p <
      0.0001). In vitro IFN inductions of 2-5OAS activity in PBMC before treatment and
      at month 3 of therapy were not significantly different. In conclusion, in vivo 2
      5OAS activity is significantly induced in patients with chronic hepatitis C, but
      endogenously produced interferon-alpha does not seem to be involved. Chronic
      induction of 2-5OAS activity results in a decreased sensitivity of PBMC to
      exogenous interferon induction. Whether this phenomenon plays a role in the
      resistance of chronic hepatitis C to interferon therapy remains uncertain.

PMID- 8564708
TI  - Distribution of immunoreactive 2',5'-oligoadenylate synthetase in mouse digestive
      tract.
AB  - 2',5'-Oligoadenylate synthetase (2-5OAS), an enzyme induced by interferon (IFN),
      has also been found in various "normal" animals that had not been treated with
      IFN. The distribution of this enzyme in the digestive tracts of normal healthy
      mice was studied by western blotting and by an immunohistochemical method using a
      specific monoclonal antibody. On western blotting, the antibody to 42 kD 2-5OA
      synthetase reacted with extracts from the stomach and intestines (small and large
      intestine), but not with extracts from the esophagus. Immunohistochemically, the
      42 kD 2-5OAS was localized on the following cells: surface mucous and parietal
      cells of fundic glands in the stomach; surface epithelial cells in the
      intestines; and some enteric nervous cells in the esophagus, stomach, and
      intestines. Treatment with IFN- alpha/beta did not essentially change the
      distribution of the enzyme in the tissues, although a small amount of the enzyme
      was detected in the esophagus by western blotting. Expression of the 42 kD 2-5OAS
      in the digestive tract may be responsible for the prevention of viral infections.

PMID- 8564709
TI  - Natural human interferon-alpha inhibits the adhesion of a human carcinoma cell
      line to human vascular endothelium.
AB  - The adhesion of cells to the microvascular endothelium is an essential step in
      the inflammatory response and metastasis. We have found that pretreatment of a
      human epidermoid carcinoma cell line, KB, with natural human interferon-alpha
      (IFN-alpha) inhibited the binding of the malignant cells to human umbilical vein
      endothelial cells (HUVEC) in a dose- and time-dependent manner. As one of several
      possible mechanisms for this inhibition, the expression of some revelant adhesion
      molecules on KB cell surfaces was examined after IFN-alpha treatment. Apart from
      a slight increase in the expression of integrin alpha 4 beta 1 (very late
      activation antigen 4, VLA-4), no changes in the expression of other adhesion
      molecules, such as sialyl Lewis X, CD44, and leukocyte function-associated
      antigen 1 (LFA-1), which is known to be a heterodimer of CD11a and CD18, were
      observed after treatment with IFN-alpha. In addition, the cell viability of KB
      was not affected by treatment of the cells with IFN-alpha, although the cell
      proliferation was markedly inhibited, indicating that the inhibitory effect of
      IFN-alpha on KB cell binding to vascular endothelium is not a result of a
      cytotoxic effect of IFN-alpha. Because the metastatic process requires not only
      the adhesion of tumor cells to vascular endothelium during their extravasation
      but also proliferation at distant sites, our findings from this in vitro
      experimental model suggest that IFN-alpha may have a potential inhibitory effect
      on tumor cell metastasis.

PMID- 8564711
TI  - Characterization of protein complexes formed on the repressor elements of the
      human tumor necrosis factor alpha gene.
AB  - Human tumor necrosis factor alpha (TNF-alpha) is an important cytokine
      responsible for pleiotropic effects in vivo. The expression of TNF-alpha is under
      both positive and negative regulation. Previously we showed that a 108 bp region
      (-280 to -172) in the TNF-alpha promoter represses TNF-alpha transcription in
      U937 cells. We also demonstrated that a smaller region of the promoter spanning
      base pairs -254 and -230 is sufficient for repressor function. This 25 bp TNF
      alpha repressor site (TRS) contains a 10 bp sequence homologous to the binding
      site of activator protein AP-2, yet it does not bind the AP-2 protein. In this
      study, we demonstrate that this 10 bp core sequence is an essential element for
      the repressor function of the TRS. Using gel retardation analysis with the 108 bp
      repressor element and the TRS as probes, multiple specific DNA binding complexes
      have been identified from U937 nuclear extracts. The complexes B, C, and D on the
      108 bp probe and the three major complexes on the 25 bp TRS probe are also
      present in Jurkat and Mono Mac 6 cells, and their abundance in these cell lines
      seems to correlate with their postulated repressor function. We have demonstrated
      that the major TRS binding proteins, with estimated MWs of 30-60 kD, copurify on
      a heparin agarose column and on a DNA affinity column conjugated with the 10 bp
      core sequence.

PMID- 8564710
TI  - Immunoprecipitation of a phospholipase D activity with antiphosphotyrosine
      antibodies.
AB  - When granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated human
      neutrophils were challenged with the chemotactic factor fMet-Leu-Phe, it was
      possible to detect a time-dependent increase in the hydrolytic (as measured by
      the production of phosphatidic acid, PA) and the transphosphatidylation (as
      measured by the production of phosphatidylethanol, PEt) activities of
      phospholipase D in intact cells prelabeled with a radioactive fatty acid. Both
      activities were inhibited by preincubation of cells with genistein. Appropriate
      conditions were developed to test the PLD transphosphatidylation activity against
      exogenous phosphatidylcholine (PCho) in an in vitro system. As in intact cells,
      increased PLD activity could be detected in cell lysates obtained from fMet-Leu
      Phe-treated cells compared with controls. When lysates were immunoprecipitated
      with antiphosphotyrosine antibodies, a PLD activity was found only in immune
      complexes that were prepared from fMet-Leu-Phe-treated cells. Conversely, no
      activity was found in lysates immunoprecipitated with an irrelevant antibody
      (GTPase-activating protein, GAP) that nevertheless was able to recognize a
      tyrosylphosphorylated form of GAP, as demonstrated by western blotting. These
      data suggest that a PCho-PLD, or a tightly bound protein, is tyrosine
      phosphorylated during cell activation.

PMID- 8564712
TI  - Exogenous interferon-gamma induces endogenous synthesis of interferon-alpha and 
      beta by murine macrophages for induction of nitric oxide synthase.
AB  - Murine macrophages (M phi) are activated either by interferon-gamma (IFN-gamma)
      or interferon-alpha/beta (IFN-alpha/beta) in combination with bacterial
      lipopolysaccharide (LPS) to induce synthesis of tumor necrosis factor alpha (TNF
      alpha) and nitric oxide synthase (iNOS) mRNA synthesis for generation of tumor
      cytotoxic nitric oxide (NO). In the present study, the effect of exogenous IFN
      gamma on the induction of endogenous mRNA synthesis and secretion of IFN
      alpha/beta by murine M phi was investigated. Neutralizing antibodies to IFN
      alpha/beta reversed TNF-alpha and NOS mRNA synthesis, as well as nitric oxide
      (NO)-mediated tumor cytotoxicity. Quantitative reverse transcription polymerase
      chain reaction (RT-PCR) revealed that treatment of M phi with IFN-gamma induced
      increases in both IFN-alpha and IFN-beta mRNA synthesis by approximately 2-fold
      and 10-fold, respectively, which corresponded to a 2-fold increase in secretion
      of IFN-alpha/beta by ELISA. These data indicate that exogenous IFN-gamma induces
      endogenous synthesis and secretion of IFN-alpha/beta by M phi, which appears to
      act in concert with endogenously synthesized TNF-alpha for the autocrine
      induction of NOS mRNA synthesis.

PMID- 8564713
TI  - Leukemia inhibitory factor binds to human breast cancer cells and stimulates
      their proliferation.
AB  - Leukemia inhibitory factor (LIF) is a cytokine that was originally described as a
      differentiation factor of a murine myeloid leukemia cell line and subsequently
      found to be an important mediator of embryonic development. Although extensively
      studied in the hematopoietic system, its effects on solid tumors are generally
      unknown. In the present study we investigated the role of LIF in human breast
      cancer cells. Using the reverse transcriptase-polymerase chain reaction, we found
      that the human breast carcinoma MCF-7 cell line expressed the message for both
      LIF receptor and its signal-transducing protein gp130, suggesting that these
      receptors might be biologically active. Binding studies with radiolabeled LIF
      demonstrated that MCF-7 cells interacted with this cytokine, and the ligand
      binding was specific and time, dose, and temperature dependent. In addition, a
      Scatchard analysis of the data revealed a single class of high-affinity (Kd 0.27
      nM) receptors with a density of approximately 430 sites per cell. MCF-7 cells
      exposed to LIF internalized and degraded the ligand. LIF stimulated the growth of
      MCF-7 as well as other estrogen-dependent and independent breast cancer cell
      lines, but the effect on normal breast epithelial lines was less significant.
      Likewise, it stimulated colony formation by breast cancer cells obtained from
      five different breast cancer patients in a dose-dependent fashion. These results
      overall suggest that human breast tumor cells express functional LIF receptors
      that play a role in breast cancer cell proliferation.

PMID- 8564714
TI  - Interleukin-10 downregulates proliferation and expression of interleukin-2
      receptor p55 chain and interferon-gamma, but not interleukin-2 or interleukin-4,
      by parasite-specific helper T cell clones obtained from cattle chronically
      infected with Babesia bovis or Fasciola hepatica.
AB  - Human recombinant interleukin-10 (IL-10) was previously shown to inhibit
      accessory cell (AC)-dependent proliferation of bovine parasite-specific T helper
      1 (Th1), Th2, and Th0 cells in an IL-2-reversible manner (Brown, W.C., Woods,
      V.M., Chitko-McKown, C.G., Hash, S.M., and Rice-Ficht, A.C., 1994. Infect. Immun.
      62, 4697-4708). The present study was therefore designed to determine whether the
      effect of IL-10 on T cell proliferation corresponded with downregulated
      expression of cytokines, or their receptors, important for T cell growth. The
      effects of IL-10 on cellular proliferation and expression of IL-2, IL-4, IL-2
      receptor (IL-2R; p55), and IFN-gamma by Babesia bovis- or Fasciola hepatica
      specific Th cell clones were simultaneously evaluated. As shown previously, IL-10
      strongly inhibited proliferation of all types of Th cell clones, although this
      did not correspond with reduced expression of IL-2 or IL-4 mRNA or their
      products. In contrast, expression of IL-2R mRNA was consistently reduced in the
      IL-10-treated clones. These results indicate that IL-10 does not inhibit AC
      dependent proliferation of bovine Th cells by downregulating T cell cytokines;
      rather, IL-10 may act by downregulating IL-2R p55 expression and subsequent
      signal transduction leading to decreased cellular proliferation. IFN-gamma
      production was also consistently downregulated in the presence of IL-10.

PMID- 8564715
TI  - Time trends in asthma and allergy: ten questions, fewer answers.

PMID- 8564716
TI  - Eosinophils and asthma. What do measurements tell us?

PMID- 8564717
TI  - Pathogenesis and management of atopic dermatitis.

PMID- 8564718
TI  - Airway permeability.

PMID- 8564719
TI  - Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren
      between 1979 and 1991.
AB  - BACKGROUND: A previous study has shown a twofold increase in prevalence of asthma
      and allergic rhinitis (AR) in Swedish recruits during the 1970s. The increase was
      higher in more northerly colder regions. OBJECTIVES: To follow up the previously
      found trend to increasing prevalences with time as well as the climatic
      variations within the country. METHODS: The prevalences of asthma, allergic
      rhinitis and eczema were assessed using two questionnaire studies, 12 years apart
      (1979 and 1991) with identical questions about the diseases. The study comprised
      representative samples of children from the Goteborg area on the south-western
      coast (in 1979: 7-year-olds, n = 4255, in 1991: 7-year-olds, n = 1649) and in
      Kiruna, a mining town in the northernmost inland mountains (in 1979: 7-year-olds,
      n = 427, in 1991: 7-9-year-olds, n = 832). In 1991 there was also a personal
      interview and a skin-prick test (SPT) on subsamples. RESULTS: The prevalence of
      all these diseases present over the last year had roughly doubled over the 12
      year period. On both occasions, most symptoms were more prevalent in the northern
      area. In 1991, the prevalence of one or more symptoms in Goteborg was 23.8% and
      32.5% and in Kiruna 29.9% and 44.8% in the questionnaire and the interview,
      respectively. CONCLUSION: Asthma, AR and eczema increase continuously in
      prevalence in Sweden and the climatic distribution of the prevalences suggests
      possible major risk factors to be found in a closed indoor climate.

PMID- 8564720
TI  - Peripheral eosinophil counts as a marker of disease activity in intrinsic and
      extrinsic asthma.
AB  - BACKGROUND: Recently it has been suggested that the bronchospasm and
      hyperresponsiveness phenomena observed in asthma are secondary to the actions of
      the eosinophils; the purpose of this study was to evaluate the relationship
      between the peripheral number of eosinophils and various markers of disease
      activity in a group of asthmatics examined in childhood (mean age 10 years) and
      early adulthood (mean age 21 years). METHODS: The relationship between eosinophil
      count and pulmonary function (FEV1), respiratory symptoms, bronchial
      responsiveness to histamine and diurnal variation in peak expiratory flow rate
      (PEF) was studied in 70 subjects with bronchial asthma, of whom 24 had intrinsic
      and 46 extrinsic asthma. Self-reported symptoms of asthma were graded on a scale
      from 0 to 5, where 0 = no symptoms within the preceding 12 months and 5 = daily
      including nocturnal symptoms, and histamine responsiveness was analysed by means
      of the dose-response slope (DRS). RESULTS: In both childhood and adulthood, a
      direct correlation was found between blood eosinophil count and symptom score (r
      = 0.69, P < 0.001 and r = 0.58, P < 0.001, respectively), whereas inverse
      correlations were observed between number of eosinophils and FEV1 % predicted (r
      = -0.75, P < 0.001 and r = -0.80, P < 0.001, respectively). Furthermore, in
      adulthood, eosinophil count was found to be significantly correlated to histamine
      responsiveness (logDRS) (r = 0.65, P < 0.001) and diurnal PEF variation (r =
      0.81, P < 0.001); these correlations were also noted after dividing the subjects
      into intrinsic and extrinic asthmatics. In both groups of subjects a significant
      inverse correlation was also found between histamine responsiveness and
      prechallenge FEV1 % predicted. The eosinophil count in childhood was weakly
      correlated to the symptom score in adulthood (r = 0.29, P < 0.02). CONCLUSIONS:
      This study showed a relationship between eosinophil count and severity of
      asthmatic symptoms, level of pulmonary function, histamine responsiveness and
      diurnal variation in PEF in both intrinsic and extrinsic asthma; suggesting that
      the peripheral eosinophil count reflects asthmatic activity, and possibly the
      degree of inflammation in the airways, in both children and adults. Furthermore,
      a low number of eosinophils in childhood might be related to a relatively
      favourable prognosis with regard to symptoms of asthma in early adulthood.

PMID- 8564721
TI  - Bee venom immunotherapy induces a shift in cytokine responses from a TH-2 to a TH
      1 dominant pattern: comparison of rush and conventional immunotherapy.
AB  - BACKGROUND: The mechanism of immunotherapy is unclear. Allergic disease is known
      to involve enhanced TH-2 cytokine responses to allergen. OBJECTIVE: In order to
      investigate the mechanisms of immunotherapy, we have examined changes in cytokine
      secretion before (13 patients) and during (nine patients) both rush and
      conventional venom immunotherapy (VIT) in bee venom allergic patients. METHODS:
      Peripheral blood mononuclear cells were stimulated in vitro with bee venom, non
      specific antigen or mitogen and secretion of IL-4 (TH-2) and IFN gamma (TH-1)
      over the culture period measured. RESULTS: Untreated patients had TH-2 responses
      to venom and TH-1 responses to antigen and strong proliferative responses to
      venom. Controls showed no response (proliferation or cytokines) to venom and the
      normal TH-1 response to antigen. VIT resulted in marked changes in cytokine
      secretion to venom, with reduction of the abnormal TH-2 response and induction of
      a TH-1 response. The pattern differed in rush and conventional VIT. One day after
      rush VIT there was a significant fall in IL-4 secretion (P < 0.01), which rose by
      3 weeks then declined. In conventional VIT there was a gradual reduction of IL-4
      production significant after 2 months and undetectable by 6 months. IFN gamma
      secretion was induced by VIT. Proliferative responses mirrored the IL-4 changes.
      One day after rush VIT there was a loss of T cells, monocytes and NK cells from
      peripheral blood. CONCLUSION: This study shows that immunotherapy shifted
      cytokine responses to allergen from a TH-2 to a TH-1 dominant pattern, suggesting
      direct effects on T cells. How these cytokine changes relate to clinical
      desensitization is not clear. In the longer term they would result in an isotype
      switch from IgE to IgG. Early changes in cytokine or chemokine production might
      downregulate mast cell or basophil reactivity and explain the rapid
      desensitization in rush VIT.

PMID- 8564722
TI  - Clonal analysis of CD4 mediated accessory function on the effector activity of
      human CD4+ T cell subsets.
AB  - BACKGROUND: It has been reported for the peripheral T cell repertoire that CD4
      molecules may enhance adhesion between T cells and antigen presenting cells and,
      through their physical association with T cell antigen receptors, contribute to
      signal transduction. OBJECTIVE: The aims of this study were to determine if the
      modulation of CD4 molecules had differential effects on T cell recognition,
      antigen induced cytokine (IL-4 and IFN gamma), release and the induction of
      specific anergy for human TH-0, Th-1 and TH-2 cells. METHODS: A panel of anti-CD4
      antibodies was examined for its ability to modulate T cell proliferation,
      cytokine production and tolerance induction in house dust mite (TH-0 and TH-2)
      and influenza haemagglutinin (TH-1) specific human CD4+ T cell clones all
      restricted by DRB1*1101 and isolated from dust mite allergic individuals.
      RESULTS: We observed that anti-CD4 antibodies may inhibit or enhance antigen
      mediated T cell proliferation, which may reflect the differential requirements of
      T cells for selective functions of CD4. Furthermore, IFN gamma and IL-4
      production was differentially modulated depending on the specificity of the anti
      CD4 antibody and the clone of T cells. However, pretreatment of T cells with anti
      CD4 antibody alone neither induced nor enhanced the susceptibility of T cells to
      peptide mediated anergy. CONCLUSION: Antigen recognition by different subsets of
      human CD4+ T cells has differential requirements on CD4, whereas the induction of
      specific anergy appeared to be independent of the functions of CD4 molecules.
      Antigen induced IFN gamma production was more susceptible than IL-4 to the
      inhibitory effects of anti-CD4 antibodies. Furthermore, it appeared that certain
      anti-CD4 antibodies can dissociate antigen induced IFN gamma and IL-4 production,
      and may downregulate IFN gamma synthesis without inhibiting antigen dependent
      proliferation.

PMID- 8564723
TI  - Sensitivity to two major allergens (Cry j I and Cry j II) in patients with
      Japanese cedar (Cryptomeria japonica) pollinosis.
AB  - BACKGROUND: Japanese cedar (Cryptmeria japonica: CJ) pollinosis is one of the
      most important allergic diseases in Japan. Recently, the second major allergen
      (Cry j II) was isolated from CJ pollen. There have been no prevalence studies of
      sensitivity to Cry j I and Cry j II among a large number of patients with
      pollinosis. OBJECTIVE: This study was conducted to evaluate the prevalence of
      sensitivity to Cry j I and Cry j II. We measured specific IgE antibodies to these
      allergens in the sera of 145 patients. Furthermore, comparison of the sensitivity
      to Cry j I and Cry j II was examined by the histamine release assay. METHODS:
      Specific IgE antibodies to Cry j I and Cry j II were assayed by a fluorometric
      ELISA. Allergen-specific histamine release was measured by a radioimmunoassay
      kit. RESULTS: More than 90% of 145 patients had specific IgE antibodies to both
      allergens, the remainder had specific IgE to either one or the other. There were
      seasonal changes in the level of specific IgE. The changes in the levels of anti
      Cry j II IgE antibodies were parallel to those of anti-Cry j I IgE. The histamine
      release assay with leucocytes from the patients demonstrated that the allergenic
      potency of the two allergens is almost the same. CONCLUSION: Cry j II is an as
      important a major allergen as Cry j I.

PMID- 8564724
TI  - Cloning, sequencing and expression in Escherichia coli of Pha a 1 and four
      isoforms of Pha a 5, the major allergens of canary grass pollen.
AB  - BACKGROUND: The pollen of canary grass, which was introduced as a pasture grass
      from Europe, is a major allergen source in the external environment of southern
      Australia. This study was performed to characterize the major recombinant
      allergens of canary grass pollen. It is anticipated that recombinant allergens
      may be useful in diagnosis and immunotherapy of grass pollen induced allergies.
      OBJECTIVE: To clone major canary grass pollen allergens and assess their
      nucleotide and amino acid sequence homologies with other grass pollen allergens.
      This sequence information may then be useful in T and B cell epitope mapping
      studies. METHODS: A canary grass pollen lambda gt11 cDNA expression library was
      constructed and screened with sera of grass-pollen-sensitive patients. IgE
      reactive clones were isolated, sub-cloned into Escherichia coli, sequenced and,
      along with the deduced amino acid sequences, compared with other sequences in
      nucleotide and amino acid databases. RESULTS: One of the clones encoded the group
      1 allergen of canary grass pollen, Pha a 1, with a deduced amino acid sequence
      identity of 88.8% with Lol p 1, from rye-grass pollen, 88.1% with Hol l 1, from
      velvet grass pollen and 86.6% with Phl p 1, from timothy grass pollen. The other
      clones (e.g. clones, 5, 14, 28, 29) encoded polymorphic forms of Pha a 5. These
      polymorphic forms showed between 60.6-95.5% nucleotide and 40.1-81.7% deduced
      amino acid sequence identities with each other. Moreover, they shared significant
      sequence identity with other group 5 allergens from rye-grass, timothy and
      Kentucky bluegrass pollens. CONCLUSIONS: Group 1 and four isoforms of group 5
      allergens of canary grass pollen have been cloned and upon sequencing
      demonstrated strong nucleotide and amino acid sequence identities with other
      group 1 and 5 grass pollen allergens.

PMID- 8564725
TI  - Is unrecognized anaphylaxis a cause of sudden unexpected death?
AB  - BACKGROUND: Serum tryptase levels reflect mast cell activation and correlate with
      anaphylactic reactions. Elevated post-mortem serum tryptase levels have been
      found in witnessed fatal anaphylaxis. OBJECTIVE: This study was designed to
      examine whether or not unwitnessed anaphylaxis may be a hitherto unrecognized
      cause of sudden unexplained death. METHODS: Mast cell tryptase was measured by
      immunoassay in 68 post-mortem sera remaining from a previous study which reported
      elevated venom-specific IgE antibodies in 22 (23%) of 94 victims of sudden
      unexpected death. Autopsies were performed in all cases. The cause of death was
      independently reported by pathologists unfamiliar with the nature of this study.
      RESULTS: Serum tryptase levels were elevated (> 10 ng/mL) in nine of 68 cases.
      The levels could not be predicted from the clinical circumstances surrounding
      death. Sera from four individuals contained both elevated tryptase and previously
      reported elevated venom-specific IgE. CONCLUSIONS: We conclude that mast cell
      activation may accompany up to 13% of sudden unexpected deaths in adults.
      Measurement of both tryptase and specific IgE antibody levels in post-mortem sera
      from persons experiencing sudden, unexpected death may identify a small subset of
      cases due to clinically unrecognized fatal anaphylaxis, including those due to
      insect stings.

PMID- 8564726
TI  - Terfenadine exerts antiallergic activity reducing ICAM-1 expression on nasal
      epithelial cells in patients with pollen allergy.
AB  - BACKGROUND: Rhinoconjunctivitis caused by pollen allergy is characterized by
      typical signs and symptoms and mucosal infiltration by inflammatory cells during
      the pollen season. It has recently been demonstrated that the adhesion molecule
      system is deeply involved in cell-to-cell interaction during the inflammatory
      response which follows allergic reactions. OBJECTIVE: The aim of the present
      study (placebo-controlled, double-blind, randomized) was the evaluation of the
      antiallergic activity of Terfenadine in the model of the allergic rhinitis due to
      natural pollen exposure. METHODS: Two groups of patients with pollen allergy were
      enrolled in this study. Ten patients were treated with Terfenadine (120 mg/die)
      for 7 days and 10 with placebo. Evaluation criteria were: (a) clinical: signs and
      symptoms (recorded daily in a diary card by patients); (b) cytological:
      inflammatory cell count (neutrophils, eosinophils, metachromatic cells) from
      nasal lavage at T0 and T7; (c) immunocytochemical: ICAM-1/CD54 expression on
      nasal epithelial cells at T0 and T7; and (d) mediators dosage (ECP-MPO) on nasal
      lavage at T0 and T7. RESULTS: As opposed to the placebo group, patients treated
      with Terfenadine showed a significant improvement of both symptoms (P < 0.022)
      and signs P < 0.001), a significant reduction of inflammatory cells infiltrate (P
      < 0.005), of ECP levels (P < 0.002) and ICAM-1 expression on nasal epithelial
      cells (P < 0.005). CONCLUSIONS: In conclusion, these data demonstrate that
      Terfenadine exerts antiallergic activity since it is able to reduce inflammatory
      cell infiltrate and downregulates ICAM-1 expression.

PMID- 8564727
TI  - Effects of IL-4 and IL-13 on total and allergen specific IgE production by
      cultured PBMC from allergic patients determined with recombinant pollen
      allergens.
AB  - BACKGROUND: Interleukin (IL)-4 and IL-13 have been shown to be potent switch
      factors for IgE synthesis in human B cells. OBJECTIVE: In this study we
      investigated the effects of recombinant human IL-4 and IL-13 on total and
      allergen specific IgE synthesis by peripheral blood mononuclear cells (PBMC) from
      pollen allergic patients and healthy control individuals. METHODS: Peripheral
      blood mononuclear cells (PBMC) from allergic patients were investigated for their
      capacity to produce allergen specific IgE in vitro. Total protein extracts from
      birch pollen and timothy grass pollen as well as purified recombinant birch
      pollen allergens, Bet v I, birch profilin (Bet v II) and recombinant timothy
      grass pollen allergens, Phl p I, Phl p II, and Phl p V were used to measure
      specific IgE-antibody synthesis in cell culture supernatants by IgE-immunoblot
      and ELISA. RESULTS: PBMC obtained from allergic patients spontaneously secreted
      allergen specific IgE in the culture supernatants. Addition of Interleukin 4,
      Interleukin 13 and anti-CD40 antibody to the cultures alone or in combinations
      significantly induced total IgE production whereas allergen specific IgE
      production was not affected. CONCLUSION: Our results indicate that the peripheral
      blood of allergic individuals contains long lived allergen specific B cells which
      have already switched to IgE production and which are not sensitive to IL-4 and
      IL-13 treatment. These results may have implications on attempts to use cytokines
      or cytokine antagonists in therapy of Type I allergy.

PMID- 8564728
TI  - Effects of PBMC-derived histamine-releasing factors on histamine release from
      human skin and lung mast cells.
AB  - BACKGROUND: A field of study which has attracted much recent interest is the
      ability of mononuclear cells and neutrophils to interact with histamine releasing
      cells by production of specific histamine releasing factors (HRFs). However,
      almost all of these studies have been performed on basophils rather than human
      mast cells. OBJECTIVE: We have investigated the effects of lyophilized fractions
      of HRF preparations on histamine release from human skin and lung mast cells.
      METHODS: Lyophilized fractions of HRF preparations include crude supernatant from
      mononuclear cell/platelet (crude), void peak from anion exchange chromatography
      column (void), second peak from anion exchange chromatography (peak 2),
      neutrophil-activating peptide-2 (NAP-2), which was purified from void peak at
      molecular weight of 8-12 kDa, and monocyte chemotactic-activating factor (MCAF).
      Mast cells were enzymatically dispersed. RESULTS: Crude (24.2 micrograms/mL-2.42
      mg/mL), void (5.4 micrograms/mL-0.54 mg/mL), peak 2 (3.5 micrograms/mL-0.35
      mg/mL), and NAP-2 (1-20 micrograms/mL) failed to release histamine from lung mast
      cells. In skin mast cells, only higher concentrations of crude and void caused
      minimal release of histamine. MCAF up to micromolar concentrations failed to have
      an effect on mast cells from either source. However, these HRFs induced histamine
      release from human basophils. We also explored whether HRFs and stem cell factor
      could act as either priming agents for each other or for anti-IgE. The response
      of skin mast cells to all these preparations was not enhanced by preincubation in
      stem cell factor at 1 ng/mL, nor did the HRFs and MCAF enhance the response of
      skin mast cells to anti-IgE. CONCLUSION: These results suggest that these HRFs
      have no significant effect on dispersed human cutaneous and lung mast cells.

PMID- 8564729
TI  - Challenge of mast cells with increasing amounts of antigen induces
      desensitization.
AB  - BACKGROUND: In vivo rush desensitization is a procedure widely employed to
      quickly desensitize allergic patients by administering increasing doses of the
      offending antigen at short intervals. The mechanism(s) underlying this process
      and the possible role of mast cells in it have not been well delineated.
      OBJECTIVE: To define an ex vivo model for rush desensitization utilizing the mast
      cell-fibroblast coculture system. METHODS: Rat peritoneal mast cells were
      cultured on 3T3 fibroblasts and were preincubated with saturating or suboptimal
      concentrations of IgE anti-DNP antibodies. Mast cells were then repeatedly
      challenged at 30 min intervals, with increasing amounts (0.001-100 ng/mL) of the
      antigen DNP-HSA, in the presence of calcium ions. Parallel control cultures were
      stimulated only once by each antigen concentration. In another set of
      experiments, mast cells were repeatedly activated with increasing concentrations
      (0.1-1000 ng/mL) of compound 48/80. Supernatants and cell sonicates were assessed
      for histamine content and the percentage of histamine released was calculated.
      RESULTS: When saturating concentrations of IgE anti-DNP antibodies were used,
      mast cells challenged repeatedly with DNP-HSA did not release significant amounts
      of histamine up to an antigen concentration of 1 ng/mL. At this stage they were
      partially desensitized, releasing only 108.3 +/- 17.1 ng histamine/plate (7.9 +/-
      0.8%). A marked desensitization was observed at optimal antigen concentration
      (100 ng/mL), where experimental mast cells released only 45.6 +/- 10.9 ng/plate,
      compared with 661.9 +/- 48.2 ng/plate in firstly challenged cultures.
      Desensitization was probably not due to mast cells histamine depletion, since the
      cells still contained large amounts of histamine (579.5 +/- 108.6 ng/plate) at
      the end of the procedure. A similar pattern of desensitization was observed when
      mast cells were preincubated with a suboptimal concentration of IgE antibodies.
      Activation of mast cells with increasing amounts of the IgE-independent
      secretagogue, compound 48/80, did not cause desensitization since at each
      concentration both repetitively challenged and control cultures released similar
      amounts of histamine. Furthermore, challenge of antigen-desensitized mast cells
      with compound 48/80 caused the release of 75.9 +/- 4.9% histamine comparable to
      the percentage of histamine released from controls (79.5 +/- 6.7). CONCLUSION:
      Repeated exposure of mast cells to gradually increasing amounts of antigen
      induces their refractoriness. This observation would suggest a role for mast
      cells in rush desensitization procedure in vivo. Our coculture system may serve
      as a useful model for studying this process.

PMID- 8564730
TI  - [Assessment of anxiolytics (6)--A novel method in mice using psychological
      stress].
AB  - Both antinociception induced by psychological stress (PSY, using the
      communication box) and the suppression by the stress of the development of
      antinociceptive tolerance to morphine were completely extinguished by diazepam
      (DZP, 1-2 mg/kg), suggesting an essential role of emotional factors in the
      underlying mechanisms. Based on these findings, a simple and selective method for
      evaluating anxiolytics was designed. Treatment with methysergide (2-20 mg/kg,
      ip), buspirone (1-10 mg/kg, ip), ritanserin (1-5 mg/kg, ip), Y-25,130 (0.03-0.1
      mg/kg, ip) and ICS 205-930 (1-100 micrograms/kg, po), all of which reportedly
      possess anxiolytic activity, dose-dependently suppressed both the production of
      PSY stress-induced antinociception (PSY-SIA) and the blockade of the development
      of morphine tolerance by PSY stress. In contrast to these compounds, (+/
      )pindolol (up to 3 mg/kg) and imipramine, even after pretreatment daily with 40
      mg/kg, ip, for 5 days, produced no such suppression. In an elevated plus-maze
      (EPM) method, frequently used as a simple method for detecting anxiolytic drugs,
      not only DZP, buspirone, Y-25,130 and ICS 205-930 but also imipramine (daily with
      40 mg/kg for 5 days) increased the time spent on the open arms, while
      methysergide or retanserin failed to augment the time, indicating that the EPM
      method is not selective for this purpose. Since U-50,488H suppresses the
      development of morphine tolerance, the utility of the compound for PSY stress was
      also examined; however, the suppressive effect was counteracted by (+/-)pindolol
      but not by ritanserin. Thus, we proposed a valid new method for screening
      anxiolytic drugs in mice, by testing the extinguishable effect of drugs on these
      parameters, i.e., PSY-SIA and suppression by PSY stress of the development of
      morphine tolerance.

PMID- 8564731
TI  - [Effects of chronic administration of antidepressants on microtubule assembly in
      rat cerebral cortex].
AB  - We examined the effects of chronic treatment with several types of
      antidepressants on microtubule assembly and phosphorylation of microtubule
      associated proteins (MAPs) in the rat cerebral cortex. The microtubule assembly
      was monitored in turbidity at 350 nm using a spectrophotometer. Chronic but not
      acute treatment with desipramine (DMI), maprotiline (MPR) or citalopram (CTR)
      inhibited microtubule assembly, assayed in the presence of protein phosphatase
      inhibitors (PPI). In contrast, this inhibitory effect was completely nullified in
      the absence of PPI. The three compounds had no direct effect on microtubule
      assembly. The phosphorylation of MAPs (MAP2 and tau) was investigated by
      immunoblotting with monoclonal antibodies (phosphoserine, phosphothreonine and
      phosphotyrosine) after immunoprecipitation of MAPs. The serine but not threonine
      or tyrosine phosphorylation of MAP2 was significantly increased after chronic
      treatment with DMI, MPR or CTR. The phosphorylation of tau was not altered
      following chronic administration of antidepressants. These results suggest that
      the inhibition of microtubule assembly observed after chronic antidepressant
      treatment is attributable to an increase in the phosphorylated MAP2 and this
      effect may represent a novel and common action of typical and atypical
      antidepressant agents. Our results show that besides second messengers system,
      protein phosphorylation might be involved in the therapeutic effects of
      antidepressants.

PMID- 8564732
TI  - [Reverse-tolerance phenomenon in methamphetamine-induced behavioral stereotypy
      and impairment of cliff avoidance reaction after subchronic methamphetamine
      administration in rats].
AB  - Clinical evidence of methamphetamine (MAP)-induced reverse-tolerance phenomenon
      is available in studies of methamphetamine psychosis. To examine the clinical
      relevance of the reverse-tolerance phenomenon as a model of this psychosis, two
      experiments were conducted using rats. In the first experiment, we examined the
      relationship of MAP (4 mg/kg/day)-induced reverse tolerance in behavioral
      stereotypy to impairment of the cliff avoidance reaction (CAR). The stereotypy
      scores by the method of Creese and Iversen reached a maximum at day 14, and were
      unchanged thereafter. Impairment of CAR appeared in 3 of 6 rats at day 21 or 28
      without motor ataxia, as rated by the scoring system of Hiramatsu et al. This
      suggested that cognitive dysfunction reflected by CAR impairment may develop
      after MAP-induced reverse-tolerance phenomenon, as evaluated by the behavioral
      stereotyping rating scale. In the second experiment, the effect of PCP (1 mg/kg)
      on CAR was examined in rats pretreated with MAP (4 mg/kg/day) for 30 days. No
      behavioral stereotypy or CAR impairment was found in these rats for 1 hour after
      PCP challenge. This showed that MAP-induced reverse-tolerance did not alter
      sensitivity to PCP in producing behavioral stereotypy or CAR impairment.

PMID- 8564733
TI  - [Expression of neurotrophin proteins in the brain, and its physiological
      significance].

PMID- 8564734
TI  - [Trial to produce animal model of Alzheimer's disease by continuous infusion of
      beta-amyloid protein into the rat cerebral ventricle].
AB  - To develop an animal model of Alzheimer's disease, we investigated the toxicity
      of beta-amyloid protein which is a component of senile plaques in Alzheimer's
      disease. beta-Amyloid was infused into the cerebral ventricle of rats for 14 days
      using a mini-osmotic pump. The performance of habituation, water maze and passive
      avoidance tasks in beta-amyloid protein-treated rats was impaired. Choline
      acetyltransferase activity significantly decreased in the hippocampus both
      immediately and 2 weeks after cessation of the infusion. However, the learning
      impairment is recoverable 2 weeks after cessation of the infusion. Both
      immediately and 2 weeks after cessation of the infusion, glial fibrillary acidic
      protein immunoreactivity increased. Further, beta-amyloid protein altered the
      staining of nuclei of cells in the hippocampus only 2 weeks after cessation.
      These results suggest that beta-amyloid protein damages the central nervous
      system in vivo, and that this animal could be used as a model of Alzheimer's
      disease.

PMID- 8564735
TI  - [Gene analysis of Huntington's disease].

PMID- 8564736
TI  - Cytogenetic analysis of prostate carcinoma by fluorescence in situ hybridization.

PMID- 8564737
TI  - Surgical treatment of renal cell carcinoma extending into the vena cava.
AB  - BACKGROUND: Renal cell carcinoma has a tendency to invade the vasculature and the
      prognostic implications of intravena caval tumor thrombectomy remains
      controversial. We reviewed our clinical experience with RCC patients who
      underwent tumor thrombectomy and radical nephrectomy. METHODS: Surgery was
      carried out in 13 renal cell carcinoma patients with inferior vena cava extension
      over the past seven years. Diagnosis of intracaval tumor extension and thrombus
      formation was made by imaging techniques including ultrasonography and computed
      tomography. Cavography and magnetic resonance imaging were also performed in some
      cases. RESULTS: The level of the tumor thrombus was infrahepatic (V2a) in nine
      cases and retrohepatic (V2b) in four. Ultrasound and magnetic resonance imaging
      were extremely useful in defining the extent of the thrombus in addition to
      detecting its presence. The caval thrombi were reached simply by ligation and
      division of the short hepatic veins in the V2a cases, but liver mobilization was
      required in the V2b cases. There were no operative deaths. Two patients who had
      metastases on surgery died of the disease eight and 13 months after surgery. Four
      of the 11 patients in whom no evidence of metastasis was found on surgery also
      died of the disease between nine and 16 months postoperatively. The remaining
      seven patients are still alive at periods of 6-74 months after surgery, with or
      without residual tumors. The nature of the intracaval tumor thrombi seems to
      affect the overall prognosis for survival. Elevated levels of acute phase
      reactants and immunosuppressive acidic protein were associated with short
      survival times. CONCLUSIONS: Our experience suggests that aggressive surgery
      should be considered in selected patients with non-metastatic renal cell
      carcinoma extending into the vena cava.

PMID- 8564738
TI  - Pulmonary nodules in patients with a history of radical nephrectomy for renal
      cell carcinoma.
AB  - BACKGROUND: Nine patients with a history of radical nephrectomy for renal cell
      carcinoma underwent surgical removal of newly detected pulmonary nodules at the
      Hiroshima University Hospital. Six patients had metastatic lung tumors two
      patients had bronchogenic primary carcinomas and one had a granulomatous
      infection. METHODS: To determine if any characteristics can distinguish a new
      primary carcinoma from metastatic renal cell carcinoma, we reviewed the nine
      patients described above. The patients with pulmonary metastases and those with
      new primary lung cancers did not differ in age, sex, history of smoking, clinical
      stage and pathological findings of the renal primary site, on the location and
      size of the pulmonary nodules. RESULTS: Only the interval between the nephrectomy
      and the appearance of the new pulmonary lesion may be a predictive factor. This
      interval was 48 and 51 months for the patients with new primary lung cancers but
      varied from 0 to 39 months for the patients with metastatic renal cell carcinoma.
      A solitary nodule had an equal chance of being metastatic or primary.
      CONCLUSIONS: These results indicate that a solitary nodule that is detected at a
      longer interval after radical nephrectomy may be a new primary lung cancer. Once
      new pulmonary nodules are identified in a patient with a history of radical
      nephrectomy for renal cell carcinoma, surgical excision is required for a final
      diagnosis before initiating therapy for metastases.

PMID- 8564739
TI  - Detection of the urine jet phenomenon using Doppler color flow mapping.
AB  - BACKGROUND: Ultrasonic Doppler color flow mapping was applied to detect urinary
      flow in this study. The purpose of the study was to provide fresh insight into
      urodynamic and functional studies of the kidney and ureter. METHODS: Ultrasonic
      Doppler color flow mapping was performed from the abdominal surface to detect the
      urine jet phenomenon from the ureteral orifice in 25 healthy men and four healthy
      boys. In the cases in which the jet phenomenon was observed, the maximum
      velocity, mean velocity, successive time and frequency were measured. In 23 of
      the 25 men, the measurement was performed under normal circumstances and during
      diuresis. RESULTS: In 23 (92%) of the 25 men and in three (75%) of the four boys,
      the urine jet phenomenon was clearly visualized under normal conditions. The
      measured maximum velocity, mean velocity, successive time and frequency on the
      left side under normal conditions for the men were 31.8 +/- 15.3 cm/sec, 20.0 +/-
      10.2 cm/sec, 2.5 +/- 1.3 sec and 1.2 +/- 0.5/min, respectively. The magnitude of
      each of these parameters was smaller in the case of the boys. CONCLUSIONS: The
      detection of the jet phenomenon by Doppler color flow mapping is a promising new
      way of examining renal or ureteral function noninvasively.

PMID- 8564740
TI  - Sequential analysis of recurrent calcium calculi by infrared spectroscopy.
AB  - BACKGROUND: While the incidence of calcium urolithiasis increases, the precise
      mechanism of calcium oxalate stone formation is still controversial. Is the
      composition of a recurrent calcium oxalate stones always the same as previous
      ones? There are few reports that specifically address the question by study of
      sequential changes of the composition of recurrent calcium calculi. METHOD: From
      our medical records 70 patients with a history of two or more recurrent episodes
      of calcium oxalate stone disease were selected and the analyses of 190 stones
      were reviewed. Infrared spectroscopic analysis was done using a Perkin Elmer 1740
      spectrophotometer. RESULTS: Calcium oxalate monohydrate were detected in 63
      stones, calcium oxalate dihydrate in 12, calcium oxalate monohydrate mixed with
      dihydrate in 28, calcium oxalate monohydrate mixed with calcium phosphate in 30,
      calcium oxalate dihydrate mixed with calcium phosphate in 20, calcium oxalate
      monohydrate mixed with dihydrate and calcium phosphate in 20, calcium oxalate
      monohydrate mixed with dihydrate and calcium phosphate in 37. Alterations of
      stone components during follow-up were found in 43 stones from 40 patients. The
      shift of a main composition from calcium oxalate monohydrate to calcium oxalate
      dihydrate was found in 24 stones and vice versa in 19 stones. CONCLUSIONS:
      Sequential changes of the compositions of recurrent calcium calculi are highly
      likely to occur with time in individual recurrent calcium stone formers. Calcium
      oxalate monohydrate was a most common component of the studied recurrent calcium
      stones.

PMID- 8564741
TI  - Plasma endotoxin concentrations in patients with urinary tract infections.
AB  - BACKGROUND: Although endotoxin elicits a variety of pathophysiological activities
      in hosts with gram-negative bacterial infections, the clinical significance of
      plasma endotoxin levels have not been clearly defined in the patients with
      urinary tract infections. The purpose of the study was to measure plasma
      endotoxin concentrations in relation to the types of urinary tract infections and
      to examine their correlation with inflammatory parameters. METHODS: Using
      chromogenic Limulus-amebocyte lysate assay, plasma endotoxin concentrations were
      measured in a total of 63 patients with various types of nonspecific urinary
      tract infections. RESULTS: The mean plasma endotoxin concentrations in patients
      with sterile pyuria, chronic complicated cystitis, acute uncomplicated
      pyelonephritis or acute exacerbation of chronic complicated pyelonephritis,
      chronic complicated pyelonephritis, and acute bacterial prostatitis or
      epididymitis were significantly higher than those in healthy individuals and in
      patients with acute uncomplicated cystitis. The correlation coefficients between
      plasma endotoxin concentrations and body temperatures, white blood cell counts in
      peripheral blood, erythrocyte sedimentation rates, and C-reactive proteins were
      0.678 (P < 0.01), 0.503 (P < 0.01), and 0.330 (P < 0.01), respectively.
      CONCLUSIONS: Patients with urinary tract infections may respond to endotoxin
      locally and generally depending on the sites of infection involved. However,
      endotoxin levels do not always correlate to clinical findings or inflammatory
      parameters.

PMID- 8564742
TI  - Factors affecting the occurrence of urothelial tumors in dye workers exposed to
      aromatic amines.
AB  - BACKGROUND: Past studies have analyzed individual jobs in dyestuff factories,
      materials manufactured and handled, age at exposure, and the duration of exposure
      in factories as factors related to the occurrence of urothelial tumors. None of
      these studies was based on long-term observation, and the factors involved in the
      occurrence of urothelial tumors remain controversial. In this study, various
      factors that may affect the occurrence of urothelial tumors in dye workers were
      assessed by multivariate analysis. METHODS: Three hundred and sixty-three workers
      in nine member factories of the Dyestuff Industrial Cooperative Association were
      included the study. Factory A is a large dyestuff chemical factory in Wakayama
      City with 218 dye workers. The other eight smaller factories employ a total of
      145 dye workers. Correlations of tumor occurrence with a variety of factors, such
      as dyestuff intermediates manufactured and handled, types of job in the factory,
      age at the beginning of occupational exposure, and the duration of exposure were
      examined by multivariate analysis using multiple logistic models. RESULTS:
      Urothelial tumors were found in 58 (16.0%) of the 363 dye workers in the nine
      member factories of the Cooperative Association examined in the present study.
      The incidence in workers in Factory A, 5.5% (12 patients), was significantly (P <
      0.01) lower than the overall incidence, while that in the eight small factories,
      31.7% (46 patients), was significantly (P < 0.01) higher than the overall
      incidence. The risk factors significantly related to tumor occurrence in the 363
      dye workers were benzidine (odds ratio, 8.302) as a dyestuff intermediate,
      manufacturing work (odds ratio, 4.631), and a long period of exposure (odds
      ratio, 1.018). Correlations of the tumor occurrence with the various factors were
      examined by multivariate analysis using multiple logistic models. In the total of
      363 workers, benzidine as an intermediate (P < 0.05), manufacturing work (P <
      0.01) and the duration of exposure (P < 0.01) were found to have contributed to
      the urothelial tumor occurrence. In Factory A, benzidine as an intermediate (P <
      0.01) and duration of exposure (P < 0.05) contributed significantly to tumor
      occurrence. CONCLUSIONS: 1) The manufacturing and handling of benzidine and
      duration of exposure contribute significantly to the occurrence of occupational
      urothelial tumor, the former more strongly than the latter; 2) the contribution
      of different job types to tumor occurrence may be dependent upon the industrial
      health and safety practices in each factory.

PMID- 8564743
TI  - En bloc radical cystoprostatourethrectomy with preservation of sexual function.
AB  - BACKGROUND: Recent understanding of the precise anatomy of the cavernous nerves
      to the penis allows us to preserve potency in men undergoing radical
      prostatectomy or radical cystoprostatectomy. A technique of urethrectomy that
      preserves potency has been also developed. To date, however, delayed urethrectomy
      has been recommended to preserve potency. We have applied a nerve-sparing
      technique to en bloc cystoprostatourethrectomy. METHODS: Seven patients have
      undergone simultaneous urethrectomy with the radical cystoprostatectomy by the
      nerve-sparing technique. Patient age ranged from 52 to 69 years (mean age, 61.3
      years). All patients were potent preoperatively. Meticulous and complete
      dissection of the membranous urethra from the pelvis is the key to preservation
      of potency at urethrectomy. RESULTS: The patients were followed for 7 to 64
      months (mean, 27.3 months). Four (57%) of the patients regained potency
      postoperatively. Two patients were able to have erections postoperatively but are
      still impotent. CONCLUSIONS: Our clinical results show that it is possible to
      perform simultaneous urethrectomy and preserve potency.

PMID- 8564744
TI  - Accuracy of prostatic volume calculation in transrectal ultrasonography.
AB  - BACKGROUND: Estimation of the prostatic volume by transrectal ultrasonography is
      now widely used to evaluate the effect of conservative treatment and to improve
      the specificity of prostate specific antigen. Accurate measurement of prostatic
      volume is necessary for the calculation of prostate specific antigen density
      (PSA/prostatic volume ratio). METHODS: Three dimensional models of the prostatic
      contour were constructed from transrectal ultrasonotomograms taken at 5 mm
      intervals in 20 cases. Using these models, the accuracy of ellipsoid volume
      calculation and prolate ellipse volume calculation were examined. For prolate
      ellipse volume calculation, prostatic length was measured in two ways; length
      (Lv) vertical to the transverse section, and length (Lp) parallel to the
      prostatic urethra. RESULTS: Ellipsoid volume calculation showed errors of about
      20%. Moreover, ellipsoid volume calculation fluctuated markedly (up to 50%) in
      accordance with the change of the scanning angle of the transverse section. The
      error of prolate ellipse volume calculation using Lp for length increased by an
      average of 25% as the angle moved away from the perpendicular. The prolate
      ellipse volume calculation using Lv for length was the most reliable method. The
      degree of error was least dependent on the angle between the plane and the axis.
      CONCLUSION: Although prolate ellipse volume calculation was more accurate than
      ellipsoid volume calculation, it is essential to have the three axes cross at
      right angles to obtain an accurate value by the prolate ellipse volume
      calculation.

PMID- 8564745
TI  - Prostate-specific antigen in mass screening for carcinoma of the prostate.
AB  - BACKGROUND: Prostate-specific antigen (PSA) has various advantages over prostatic
      acid phosphatase (PAP) as a marker for prostate cancer, but its role in prostate
      cancer mass screening remains controversial. We measured serum PSA in addition to
      serum PAP determination and digital rectal examination (DRE) in our mass
      screening program to assess the usefulness of PSA for prostate cancer mass
      screening. METHODS: Serum PSA and PAP measurements and DRE were performed in 1249
      patients in mass screening for carcinoma of the prostate in 1989 and 1990.
      Thirteen cancers were diagnosed. We calculated the mean plus standard deviations
      (2SD) of the PSA and PAP values of men without cancer, and assessed the
      usefulness of PSA for prostate cancer screening by using these figures as the
      upper limit of normal. RESULTS: The number positive for PSA, PAP and DRE were 39,
      36 and 48, respectively. If our screening had been performed without DRE, three
      cancers would have remained undetected, and the number would have been the same
      if performed without PSA. If the screening had been performed without PAP, on the
      other hand, no cancers would have remained undetected. The sensitivities of PSA
      and PAP were 54% and 23%, respectively. The screening detection rate with DRE and
      PSA was 0.88%, and with DRE and PAP was 0.64%. CONCLUSIONS: Measurement of serum
      PSA values with adjustment of the cut-off value was considered more useful than
      PAP in mass screening for prostate cancer.

PMID- 8564746
TI  - Single-step purification of prostatic acid phosphatase: immunoaffinity
      chromatography with a monoclonal antibody.
AB  - BACKGROUND: Prostatic acid phosphatase (PAP) is an important protein which should
      be studied further as a tumor marker or as a biologically functional molecule.
      The purpose of the study was to establish a simple and reliable method to obtain
      highly pure PAP. METHODS: Spleen cells from mice immunized with prostatic
      epithelial cells prepared from benign prostatic hyperplasia tissue were fused
      with myeloma cells X63Ag8-653. Hybrid cells of interest were selected using the
      indirect immunofluorescence method with unfixed frozen tissue sections. One clone
      of the hybrid cell lines was established which secreted the monoclonal antibody
      specifically reactive to prostatic acid phosphatase. Using this monoclonal
      antibody, we purified the antigen from human prostatic tissue by means of single
      step immunoaffinity chromatography. RESULTS: SDS-PAGE profiling under reducing
      conditions indicated that the protein recognized by this antibody consisted of
      several components of molecular weight 41,000-45,000. Partial amino acid sequence
      analysis of this protein indicated that these components involved a
      heterogeneously modified single polypeptide, and that this antigen is identical
      to human prostatic acid phosphatase. CONCLUSIONS: This single-step method saves
      the time needed to purify prostatic acid phosphatase and requires only half a day
      for the whole procedure. Moreover, the purity of the isolated protein was
      extremely high. This method seems to be useful not only for purifying prostatic
      acid phosphatase but also for purifying other proteins from the prostate gland
      and for analysis of antigenic macromolecules.

PMID- 8564747
TI  - Continence mechanism of the orthotopic neobladder: urodynamic analysis of
      ileocolic neobladder and external urethral sphincter functions.
AB  - BACKGROUND: The main objectives of bladder substitution are the preservation of
      the upper urinary tract and maintenance of urinary continence. Orthotopic bladder
      substitution makes it possible to achieve urinary continence as well as normal
      passage of urine through the urethra. Creation of a low pressure reservoir and
      careful preservation of the distal sphincter mechanism are considered to be of
      utmost importance for the maintenance of urinary continence after orthotopic
      bladder substitution. However, sphincter behavior after orthotopic bladder
      substitution has not been fully elucidated. The purpose of this study was to
      evaluate the vesicourethral continence mechanism after orthotopic bladder
      substitution in male patients. METHODS: Urodynamic evaluation was performed in 14
      male patients after cystoprostatectomy for bladder cancer and an ileocolic
      neobladder using a cecourethral anastomosis. RESULTS: Good continence was
      achieved in 86% (12/14) of the patients during the day and in 79% (11/14) at
      night. On cystometry, maximum capacity of the neobladders was 434 +/- 21 ml (mean
      +/- SEM), and basal pressure at maximum capacity was 15.6 +/- 0.9 cm water.
      Phasic neobladder contraction with amplitudes ranging from 14 to 40 (26.6 +/-
      2.7) cm water were noted in 11 of 14 patients. Sphincter electromyography
      demonstrated an increase in the frequency of action potentials of the external
      urethral sphincter during neobladder filling from empty to 80% of capacity (from
      8.9 +/- 1.6 to 14.6 +/- 2.1 spikes per second; mean percentage increase, 64%, in
      patients with daytime continence). Maximum urethral closure pressure on urethral
      pressure profile was 49.9 +/- 3.5 (range, 30 to 64) cm water in patients with
      daytime continence, while in two patients who were incontinent during the day and
      at night maximum urethral closure pressure was lower (16 and 24 cm water) and the
      recruitment of action potentials of the external urethral sphincter during
      neobladder filling was impaired (percentage increase, 15% and 20%). CONCLUSIONS:
      An ileocolic neobladder has characteristics of a low pressure reservoir with a
      satisfactory continence rate. The vesicourethral continence reflex is well
      preserved in patients with continence after orthotopic bladder substitution.

PMID- 8564748
TI  - Alteration of the hypothalamus-pituitary-testis axis in oligozoospermic men with
      normal gonadotropin levels.
AB  - BACKGROUND: Serum basal hormone levels such as lutenizing hormone (LH), follicle
      stimulating hormone (FSH), and testosterone, which is important to regulate
      testicular function, do not necessarily indicate the normal integrity of the
      hypothalamic-pituitary-testicular axis and the static measurement is not enough
      to detect the endocrine disorder. The dynamic measurement of gonadal hormone by
      GnRH test is considered to be more helpful to understanding the endocrine
      regulation of spermatogenesis. In this study, we performed GnRH test in
      oligozoospermic patients with normal levels of LH and FSH to examine the subtle
      alteration of hypothalamic-pituitary-testis axis. METHODS: GnRH test was
      performed in 41 patients with oligozoospermia and normal gonadal hormone levels.
      RESULTS: The responses of LH and/or FSH were excessive in most patients in spite
      of their normal gonadotropin levels. The patients with sperm concentration < 10 x
      10(6)/ml had significantly higher peak levels of both LH and FSH than did those
      with sperm concentration > 10 x 10(6)/ml. In the patients with normal peak levels
      of both LH and FSH, sperm concentration was significantly higher than those with
      exceeded peak levels of FSH and/or LH after GnRH test. No significant differences
      were observed in estradiol, testosterone, free testosterone, or prolactin (PRL)
      levels between patients with normal responses and abnormal responses of LH and/or
      FSH. CONCLUSIONS: The feedback control of gonadotropin release from testis was
      worse in more severely oligozoospermic patients, although the precise mechanism
      of feed back still remains unknown.

PMID- 8564749
TI  - Renocolic fistula caused by xanthogranulomatous pyelonephritis.
AB  - A 68-year-old female was diagnosed with a renocolic fistula, associated with left
      chronic pyelonephritis due to a ureter stone. Nephrectomy and repair of the
      fistula were performed. Histopathological examination revealed
      xanthogranulomatous pyelonephritis.

PMID- 8564751
TI  - Hospice: one choice for the end-stage head and neck cancer patient.

PMID- 8564750
TI  - Renal oncocytoma containing "chromophobe" cells.
AB  - We report a rare case of renal oncocytoma containing occasional "chromophobe"
      cells. This case suggests an intimate relationship between oncocytoma and
      "chromophobe" renal cell carcinoma.

PMID- 8564752
TI  - Generalist vs. specialist--a step forward or a step backward?

PMID- 8564753
TI  - It is time for nursing.

PMID- 8564755
TI  - Highlights of President Clinton's health care plan.

PMID- 8564754
TI  - Head-and-neck surgery.

PMID- 8564756
TI  - Unilateral vocal cord paralysis.

PMID- 8564757
TI  - Trismus: its causes, effects and treatment.
AB  - This article describes trismus and some of its causes. Trismus is most frequently
      observed in head and neck cancer patients and postsurgical patients, but can also
      be found in those suffering from trauma, including burns and gunshot wounds.
      Effects include impaired nutrition, oral hygiene and lifestyle. The
      pathophysiology of trismus is reviewed, a method of assessment is presented, a
      clinical study examining mobilization regimens is summarized, and suggestions for
      treatment are described.

PMID- 8564758
TI  - Maslow's Hierarchy of Needs and the individual with chronic vestibular
      dysfunction.
AB  - Individuals with chronic vestibular dysfunction may have unmet physiological or
      safety needs on a chronic basis. Their inability to fulfill the basic needs and
      progress to higher needs can lead to a patient population with many psychosocial
      problems. Very often such problems are ignored or unrecognized or are
      misdiagnosed, and treated inappropriately. This disruption in the individual's
      life can lead to an inability to progress as a human being. Nursing assessment
      and appropriate interventions should be developed to treat psychosocial problems
      in this patient population. The nursing profession should serve patients with
      vestibular dysfunction through direct care, teaching, counseling, support group
      facilitation, and research into appropriate interventions.

PMID- 8564759
TI  - Facilitating smoking cessation: the nurse's role.
AB  - Smoking has been implicated in the pathogenesis of head and neck cancer. Patients
      who continue to smoke after head and neck cancer therapy are at an increased risk
      for second primary cancers, recurrences, poorer response to therapy, and possibly
      shortened survival. Approximately 30% of cancer patients resume smoking within
      the first year after cancer therapy. The purposes of this article are to discuss
      the perils of smoking for the head and neck cancer patient who has undergone
      treatment and to examine the role of the nurse in assisting with smoking
      cessation. Smoking cessation among head and neck cancer patients is complicated
      by possible functional or psychological deficiencies. Some methods for assisting
      patients to cease smoking can be incorporated into nursing practice and
      suggestions on how to implement them are presented.

PMID- 8564760
TI  - ORL-head and neck nursing: a specialty of opportunity.

PMID- 8564761
TI  - Excellence in clinical practice: a time for recognition.

PMID- 8564762
TI  - The reforming of health care in America: jacta est alea.

PMID- 8564763
TI  - Botulinum toxin therapy for blepharospasm in the otolaryngology clinic.
AB  - The use of botulinum toxin (Botox, Allergan, Inc.) is a treatment for spasmodic
      conditions involving many structures in the head and neck. Proper reconstitution,
      storage, preparation and administration of Botox are important aspects of its
      use. This article focuses on the actual preparation and sites of injection of
      Botox as well as the authors' clinical experiences in using it.

PMID- 8564764
TI  - Postoperative care of the maxillectomy patient.
AB  - Guidelines for preoperative patient information and immediate postoperative care
      of the maxillectomy patient are discussed. Physical therapy, oral hygiene
      procedures, and current materials for surgical obturation and their uses are
      reviewed. Effective treatments for infections that arise in the surgical defect
      are highlighted.

PMID- 8564765
TI  - Optivite as a nutritional supplement.

PMID- 8564766
TI  - Practice guidelines. Hearing loss. Society of Otorhinolaryngology and Head-Neck
      Nurses.

PMID- 8564767
TI  - Practice guidelines. Chemosensory dysfunction (Smell and taste disorders) Society
      of Otorhinolaryngology and Head-Neck Nurses.

PMID- 8564768
TI  - Practice guidelines. Total laryngectomy. Society of Otorhinolaryngology and Head
      Neck Nurses.

PMID- 8564769
TI  - ORL nurses can make a difference.

PMID- 8564770
TI  - An overview of major health care reform proposals.
AB  - The health care reform movement continues to capture the attention of the
      American public as a variety of sweeping health care reform proposals are making
      their way through Congress. The details of these various reform plans should be
      of interest to nurses, who have both a vested interest in the health care of the
      American public and concern over the role of the nurse as a provider in any
      reformed system. This article presents a capsule of the major reform proposals,
      reviews nursing's criteria for health care reform, and suggests strategies for
      the involvement of the individual nurse in this exciting time of change.

PMID- 8564771
TI  - Care of the patient with carotid body tumors.
AB  - The carotid bodies, located at the bifurcation of the carotid arteries, rarely
      develop neoplasms or carotid body tumors. The most interesting aspects of this
      rare tumor are its anatomical location, familial tendency, physiologic
      alterations related to removal, and surgical management. Tumors of the carotid
      body can occur alone or bilaterally. Prompt and accurate diagnosis is essential
      so that resection can be done in the early stage of the disease. Nurses must be
      aware of the risks and potential complications that may be encountered after
      surgical excision of this tumor.

PMID- 8564772
TI  - Laser-assisted uvulopalatoplasty in the outpatient setting.
AB  - Snoring is a noisy social problem that affects millions of people. In the past,
      heavy snorers who sought medical assistance have been treated with numerous
      devices and machines, or by the surgical reshaping of the soft palate and uvula.
      The use of a laser for surgery in the outpatient setting provides another
      alternative in the treatment of individuals with heavy snoring.

PMID- 8564773
TI  - Practice guidelines. Stapedectomy. Society of Otorhinolaryngology and Head-Neck
      Nurses.

PMID- 8564774
TI  - Practice guidelines. Sinusitis. Society of Otorhinolaryngology and Head-Neck
      Nurses.

PMID- 8564775
TI  - Practice guidelines. Tracheostomy. Society of Otorhinolaryngology and Head-Neck
      Nurses.

PMID- 8564776
TI  - Changes in health care.

PMID- 8564777
TI  - ORL nurses in advanced practice: the wave of the future.

PMID- 8564778
TI  - Congressional committees: congress at work.
AB  - Among many people, the term "committee" holds a negative connotation. In
      Congress, however, committees hold the key to passage of any piece of
      legislation. Understanding committee structure and function is essential in
      wielding influence on committee outcomes. This article is designed to better
      acquaint the ORL nurse with key health-related Congressional committees currently
      involved in drafting health care reform proposals. In addition, the path
      legislation follows from introduction to passage is schematically reviewed.

PMID- 8564779
TI  - Characteristics of muscarinic cholinoceptors in airways of antigen-induced airway
      hyperresponsive rats.
AB  - The antagonist and agonist binding sites of muscarinic receptors were
      investigated by using membrane preparations of airways from nonsensitized normal
      control, sensitized control and repeatedly antigen challenged rats. The in vitro
      bronchial responsiveness to ACh was markedly increased in repeatedly antigen
      challenged group but not in sensitized control group. No significant difference
      was observed in receptor density and antagonist affinity among these three
      groups. The affinity of ACh for high-affinity agonist binding sites of repeatedly
      antigen challenged group was much greater than those in the other groups; the
      affinity significantly reduced in the presence of GTP gamma S. We concluded that
      enhanced G protein level might be involved in inducing airway hyperresponsiveness
      in rats.

PMID- 8564780
TI  - Effect of copper on blood coagulation of Oreochromis mossambicus (Cichlidae).
AB  - The effect of copper on the blood coagulation in freshwater fish, Oreochromis
      mossambicus was investigated. These fish were exposed to sublethal copper
      concentrations over short-term (96 hr) and long-term (4 wk) periods, at 29 +/- 1
      degree C (summer) and 19 +/- 1 degree C (winter), in experimental flow-through
      systems. Copper concentrations applied during short-term exposures were 0.16 mg/l
      and 0.40 mg/l, respectively, while 0.40 mg/l copper was applied during the long
      term exposures. After a photocymographic observation of blood, during all the
      phases of coagulation was made, it was evident that there were delays in the
      blood coagulation times, as well as decreases in the shear modulus (elasticity)
      of the clots formed, after the exposure of the fish to copper concentrations at
      both temperatures. Copper was found to induce haemophilia at 29 +/- 1 degree C
      and 19 +/- 1 degree C, while at the latter it also induced thrombocytopenia. Thus
      exposure to copper lead to coagulation defects, which caused haemorrhage in the
      body tissue, which can eventually cause the death of those fish.

PMID- 8564781
TI  - Effect of the beta 2-adrenergic agonist clenbuterol on the growth of fast- and
      slow-twitch skeletal muscle of the dystrophic (C57BL6J dy2J/dy2J) mouse.
AB  - Clenbuterol (4mg/kg in diet for 21 days) had no statistically significant effect
      on whole body growth. It did cause a significant increase (18.2%) in wet weight
      of the fast twitch muscle extensor digitorum longus (EDL) and a corresponding
      14.9% increase in total muscle protein. In transverse sections through dystrophic
      muscle fibre sizes were more variable than in normal muscle. Clenbuterol
      treatment resulted in a reduction in the proportion of small diameter fibres, and
      therefore an increase in mean fibre diameter, in dystrophic EDL. Clenbuterol had
      no significant effect upon the slow twitch muscle soleus.

PMID- 8564782
TI  - Comparative nephrotoxic effects of cis-platinum (II), cis-palladium (II), and cis
      rhodium (III) metal coordination compounds in rat kidneys.
AB  - A Sprague-Dawley rat kidney perfusion technique was used in situ to study the
      effects of cis-dichloro-diamine platinum, PdCl2 (2,6-diaminopyridine), and RhCl3
      (2,6-diaminopyridine) on sodium and calcium retention in the whole kidney. The
      technique involves perfusion of both kidneys via the abdominal aorta and then
      through the right and left renal arteries and dorsal aorta. Compared to controls,
      kidneys perfused independently with the three coordination compounds showed
      approximately equal to 45% decrease and approximately equal to 117% increase in
      Na+ and Ca2+ retention, respectively. Perfusates containing the coordination
      compounds in addition to 15 mM ouabain showed approximately equal to 76% decrease
      in Na+ and insignificant increase in renal Ca2+ retention. Hence, one can rule
      out the presence of voltage-gated Ca(2+)-channels at the basolateral side due to
      membrane depolarization. These results suggest that the three metal coordination
      compounds showed identical nephrotoxic effects on the handling of Na+ and Ca2+
      ions by inhibiting both the Na(+)-Ca(2+)-anti-porter and the Na(+)-H(+)-exchanger
      with laxing effects on nonvoltage-gated Ca(2+)-channels at the basolateral side.
      However, their effects on the Na(+)-K(+)-ATPase and the Na(+)-Ca2+ symporter was
      insignificant.

PMID- 8564783
TI  - The zeta protein kinase C isoform from the testis of the grey mullet Mugil
      cephalus with a specific reaction protein of M(r) 48,000 on oolemma.
AB  - The zeta protein kinase C isoform (PKC-zeta) was purified from the testis of the
      grey mullet Mugil cephalus and has relative masses (M(r)) of 65,000 and 63,000.
      The subunits of PKC-zeta from spermatozoa degenerated to M(r) 58,000 and 53,000
      after continuous freezing and thawing. Proteins of M(r) 48,000 on the oolemma of
      the grey mullet Mugil cephalus were found to be the reaction proteins of the PKC
      zeta from spermatozoa.

PMID- 8564784
TI  - GIP and GLP-1(7-36)amide secretion in response to intraduodenal infusions of
      nutrients in pigs.
AB  - Investigation of nutrient stimulation of two gut hormones GIP (glucose dependent
      insulotropic polypeptide) and GLP-1(7-36)amide (the active truncated form of
      glucagon-like peptide-1) is made difficult by the differential control of gastric
      emptying. Direct nutrient infusion into the duodenum was therefore carried out on
      three female pigs. The infusates consisted of saline (0.85 g or 1.7 g/100 ml);
      glucose (20 g or 40 g/100 ml); fat (30 g or 60 g/500 ml) and glucose/fat (20 g
      and 30 g or 40 g and 60 g per 1000 ml). Plasma glucose levels were elevated as
      expected by glucose or glucose/fat infusions, and they were not affected by the
      presence of fat in the infusate. Insulin secretion was stimulated in the presence
      of glucose or glucose/fat. Plasma triacylglycerol was elevated following fat and
      glucose/fat infusions. The greatest stimulus for GIP secretion was glucose/fat (P
      < 0.05); fat alone was a poor stimulus for GIP secretion, but glucose was a
      potent stimulus. GLP-1(7-36)amide was moderately stimulated by glucose and
      markedly stimulated by fat and glucose/fat infusions (P < 0.05). We conclude
      that, in pigs, dual nutrient infusion of glucose/fat is a strong stimulus for
      both GIP and GLP-1(7-36)amide secretion. The hormones therefore have the
      potential to play an important physiological role, both in the stimulation of
      insulin secretion and in adipose tissue metabolism in pigs.

PMID- 8564785
TI  - Phosalone poisoning on the cation-linked ATPases of central nervous system of
      Rana tigrina (Daudin).
AB  - An acute dose of phosalone, an organophosphate pesticide, widely used in crop
      fields, injected to Rana tigrina, intraperitoneally, inhibited the different
      inorganic ion linked ATPase enzymes of the central nervous system (CNS). Six
      discrete CNS compartments, namely telencephalon, mid-brain, rhombencephalon,
      cervical spinal cord, thoracic spinal cord and lumbar spinal cord showed markedly
      diminished ATPase activity. ATPases inhibition affected the neuronal activity and
      muscular coordination leading to moribund or comatose phase in the poisoned
      frogs. The specific inhibition of Mg(2+)-ATPase suggests the uncoupling action of
      the compound in the neuronal tissue. Increased oxygen uptake in the brain regions
      of phosalone-treated frogs also supports the above uncoupling action.

PMID- 8564786
TI  - Comparison of gentamicin nephrotoxicity between rats and mice.
AB  - Toxic effects of gentamicin administration (10-80 mg/kg body weight,
      subcutaneously (s.c.), once daily for 7 days) on several enzyme activities of
      kidney and duodenal mucosa together with other parameters were compared between
      male rats and mice. In Wistar rat kidney, tubular brush border Mg(2+)-dependent,
      HCO3(-)-stimulated ATPase (Mg(2+)-HCO3(-)-ATPase) activity was inhibited by 40-80
      mg/kg gentamicin in an almost dose-dependent manner with no changes in microsomal
      Mg(2+)-Na(+)-K(+)-ATPase activity. Cytosol carbonic anhydrase (CA) activity was
      inhibited only by 80 mg/kg gentamicin. In rat duodenal mucosa, Mg(2+)-HCO3(-)
      ATPase and CA activities were unchanged by any dose of gentamicin. Rat serum urea
      nitrogen (UN), GOT and GPT concentrations and urinary N-acetyl-beta-D
      glucosaminidase (NAG) activity were significantly increased by 80 mg/kg
      gentamicin. In ddY mice, however, almost all parameters described above were
      unaffected by gentamicin except for the urinary NAG activity which was increased
      only by 80 mg/kg gentamicin. The concentration of gentamicin in cytosol of rat
      whole kidney was approximately 3.4-fold higher compared with that in mouse kidney
      after 80 mg/kg treatment. In light microscopic analysis, 80 mg/kg gentamicin
      produced necrosis in the greater part of rat kidney proximal tubuli with no
      pathological findings in mouse kidney. In conclusion, Mg(2+)-HCO3(-)-ATPase
      activity in brush border membrane of rat proximal tubuli was selectively damaged
      in gentamicin nephrotoxicity, indicating that the rats are the suitable model for
      studies of gentamicin nephrotoxicity in humans.

PMID- 8564787
TI  - The effect of the alpha 2-adrenoceptor agonist, guanfacin, on energy expenditure,
      intake and deposition in rats.
AB  - The effect of guanfacin on the energy expenditure, food intake and body
      composition of female Wistar rats at maintenance was studied. Rats on a
      restricted food intake (about 75% of ad libitum), treated for 6 days with twice
      daily injections of guanfacin.HCl (0.5 mg/kg) showed large reductions in energy
      expenditure (30%, p < 0.001) compared to control animals but no significant
      differences in liveweight gain, dry mass gain, or gains in total body energy
      content, protein, fat and ash. The treated group had a lower intake of
      metabolizable energy (9%, p = 0.01) partially due to a lower intake of food.
      However, this lower intake of energy did not fully account for the lowered energy
      expenditure in the treated animals. The unaccounted lowered energy expenditure
      was not due to changes in the diurnal pattern of energy expenditure since
      continuous indirect calorimetry with rats fed ad libitum, over 3 days, showed
      that twice-daily injections of guanfacin (0.5 mg/kg per injection) achieved a
      sustained decrease in energy expenditure. The lack of an increased growth rate of
      rats treated with guanfacin was attributed to behavioural changes; to a decreased
      food intake and to other, unknown, factors related to energy expenditure.

PMID- 8564788
TI  - Cadmium-binding proteins from a tunicate, Pyura stolonifera.
AB  - The determination of cadmium levels in tissues of the tunicate Pyura stolonifera
      collected from uncontaminated sites revealed highest concentrations in the liver.
      After keeping P. stolonifera under laboratory conditions in Cd-containing water
      for 15 days, cadmium accumulated most markedly in liver tissue. Liver tissue of
      Cd-exposed specimens was used for the isolation of Cd-binding proteins. Five Cd
      binding proteins, which differ in their chromatographic properties, could be
      purified. At least four of these Cd-binding proteins are heat stable and cysteine
      rich. The N-terminal sequence (Met-Asp-Pro-Cys-Asn-Cys-Ala-Glu...) of at least
      two of these peptides resembles fish (plaice) metallothionein. Unlike vertebrate
      metallothioneins, P. stolonifera Cd-binding proteins are not N-terminally blocked
      by acetylation of methionine.

PMID- 8564789
TI  - Muscarinic cholinergic receptors in brain and atrial membranes of adult brook
      trout (Salvelinus fontinalis) measured by radioligand binding techniques.
AB  - Muscarinic cholinergic receptors were measured by radioligand binding techniques
      in crude membrane particulate preparations of brain and atrial tissues from
      laboratory reared brook trout (Salvelinus fontinalis). The radioligand [3H]N
      methyl scopolamine was used to determine number and affinity of receptors in
      saturation experiments. The affinity of the radioligand did not differ in brain
      and atrial preparations (96 +/- 8 and 60 +/- 4 pM, respectively). However, the
      number of binding sites was greater in atrium compared with brain (269 +/- 19 and
      166 +/- 7 fmol/mg protein, respectively). The rank order of potency of competing
      drugs in inhibition experiments was similar for antagonists with atropine > or =
      scopolamine > pirenzepine. Pirenzepine, an M1-selective drug had a 3-fold higher
      affinity in brain than atrium. The agonists oxotremorine and carbachol each bound
      to two sites in both tissues. In contrast, pilocarpine bound to only one site in
      brain and two in atrial tissue. These results are compared with those observed in
      other nonmammalian species and discussed with reference to conservation of
      proteins that serve important cellular roles.

PMID- 8564790
TI  - Dieldrin modifies the hydrolysis of PIP2 and decreases the fertilization rate in
      Bufo arenarum oocytes.
AB  - Carbachol treatment in Bufo arenarum oocytes decreases the radioactivity in
      [32P]PIP2 in the following 20 min after stimulation and increases the
      [3H]glycerol labeling of 1,2-DAG at 1 min of stimulation. On the contrary, in
      Dieldrin treated oocytes carbachol stimulation produces an increase in [32P]PIP2
      labeling without changes in [3H]1,2-DAG radioactivity. The sustained hydrolysis
      of PIP2 observed in Control oocytes is necessary to generate the intracellular
      second messengers which initiate the fertilization pathway. The lack of response
      to muscarinic stimulation in Dieldrin treated oocytes, may be associated with an
      early activation of PIP2-PLC by the insecticide, producing a depletion of the
      PIP2 pool previous to the stimulation with carbachol. These changes take place
      simultaneously with a decrease in the ability of Bufo arenarum oocytes to be
      fertilized in vitro, suggesting a correlation between impairment in the PIP2
      cascade and a decrease in the fertilization rate.

PMID- 8564791
TI  - Chicken GnRH-II and salmon GnRH effects on plasma and testicular androgen
      concentrations in the male frog, Rana esculenta, during the annual reproductive
      cycle.
AB  - In the frog, Rana esculenta, two molecular forms of GnRH, coeluting with chicken
      (c) GnRH-II and salmon (s) GnRH, have been detected using HPLC and
      radioimmunoassay. Mammalian (m) GnRH seems to be also present. In amphibians the
      role of cGnRH-II seems to be primarily the involvement in the regulation of
      neuroendocrine processes and, while the mGnRH has been postulated to act as a
      neurotransmitter and/or neuromodulator, the activity of sGnRH-like material has
      not been investigated. Therefore, we have treated the frogs with single or
      multiple injections of cGnRH-II or sGnRH (6 micrograms) or both peptides (6
      micrograms of each) to detect differences in the response measured as testicular
      or plasma androgen (testosterone plus 5 alpha-dihydrotestosterone) concentration
      during the annual reproductive cycle. The basal profile of testicular and plasma
      androgen shows that the spring peak disappeared in control animals given multiple
      injections and kept in short-term captivity. We show in the treatment with cGnRH
      II and/or sGnRH that the effects of the peptides depend on the season, the
      experimental design, and the tissue in which androgen levels were measured. In
      particular, both peptides strongly stimulate androgen production during the
      autumn-winter period, the time of the greater response to the GnRHs when basal
      levels of steroids are highest.

PMID- 8564792
TI  - Anti-lymphoproliferative activity of brown adipose tissue of hibernating ground
      squirrels is mainly caused by AMP.
AB  - A fraction with mol wt < 1 kDa was obtained from the brown fat of hibernating
      ground squirrels (Citellus undulatus) by means of delipidization, acid
      extraction, ultracentrifugation and ultrafiltration. This fraction suppressed the
      proliferation of mouse lymph node cells under standard mitogenic stimuli for T
      lymphocytes. In contrast, the fraction with mol wt < 1 kDa obtained from the
      brown fat of active ground squirrels in spring did not display such activity.
      Further HPLC purification of the biologically active fraction and chemical and
      structural analysis of its most potent antilymphoproliferative component revealed
      that this is adenosine 5'-monophosphate (AMP). These data lend support to the
      notion that in hibernating mammals AMP originating, at least partly, from the
      brown fat down-regulates the seasonally-dependent proliferation of the thymus.

PMID- 8564793
TI  - Is bone mineral density advantage maintained long-term in previous weight
      lifters?
AB  - This cross-sectional study was done in order to ascertain whether there is a
      lifelong beneficial effect on bone mineral density (BMD) of early, long-lasting,
      and intense physical exercise. Forty-eight male ex-weight lifters, mean age 64
      years (range 50-79) participated. They had followed a training program of an
      average of 10 hours/week (range 4-20) for an average of 13 years (range 1-34).
      They had all retired from competitive sport an average of 30 years (range 7-50)
      ago. Sixty-six age-matched volunteers served as controls. The bone mineral
      density (BMD, areal density, g/cm2) in the total body, spine, and hips and the
      fat content and lean body mass were measured with the LUNAR DPX bone mass
      scanner. In ex-weight lifters 50-64 years of age, the BMD was greater than in
      controls. After 65 years, no difference was found between the former weight
      lifters and their controls.

PMID- 8564794
TI  - Intact parathyroid hormone levels in renal insufficiency.
AB  - To define the onset of the rise in intact parathyroid hormone (PTH) levels in
      renal insufficiency, we conducted a cross-sectional study of parameters of
      mineral metabolism in patients with varying degrees of renal impairment. Using an
      immunoradiometric assay to measure intact PTH levels, we found elevations in
      intact PTH levels as creatinine clearance approaches 60 ml/minute (serum
      creatinine near 1.8) and a significant inverse relationship between indices of
      renal function and intact PTH levels (r = -0.60, P < 0.001 for intact PTH and
      creatinine clearance.) Calcium and phosphate levels correlate less strongly with
      the degree of hyperparathyroidism (r = -0.39, P < 0.001 for total calcium; r =
      0.31, P < 0.05 for phosphate). As a group, only patients with severe renal
      failure (creatinine clearance < 20 ml/minute) had 1,25-dihydroxyvitamin D levels
      below normal (11 +/- 4 [SEM] pg/dl, normal range 15-60). Intact and n-terminal
      PTH measurements correlate well in this patient population with varying degrees
      of renal insufficiency (r = 0.9, P < 0.001). Intact PTH can be elevated in
      patients with mild to moderate renal insufficiency, thus efforts to prevent the
      development of secondary hyperparathyroidism in renal failure should be
      undertaken early in the course of renal insufficiency.

PMID- 8564795
TI  - Age-related changes of whole skeleton and body composition in healthy men.
AB  - We examined age-related changes of the entire skeleton and its major anatomical
      areas (spine, trunk, pelvis, arms, legs) in 139 healthy males (19-99 years of
      age) and evaluated the influence of lean mass and fat mass on these changes. The
      population studied was stratified according to their ages referred in decades.
      Bone mineral density (BMD) and body composition (fat mass, lean mass) were
      measured by Lunar DPX. A negative linear correlation between BMD values and age
      was observed. The overall bone loss from the young to the aged was statistically
      significant for all skeletal sites, with a lower level of significance for the
      spinal area: BMD percentage decrease ranged from 19.4% for the pelvis to 9% for
      the spine. Peak bone mass was observed in the first decade (19-29 years of age).
      Soft tissue increased until the fifth and sixth decades, followed by a gradual
      decrease. Lean mass declined in a uniform way from the first to the last decades.
      BMD values were significantly related to lean mass, but there were no
      correlations with the fat mass. Lean body mass was significantly related to
      BMD/height, index of "true" volumetric density. Multiple regression analysis
      confirmed that in males the principal determinant of total body bone density is
      fat-free mass.

PMID- 8564796
TI  - Effect of femoral rotation on bone mineral density measurements with dual energy
      X-ray absorptiometry.
AB  - Precision in femoral neck scans with dual energy X-ray absorptiometry (DXA) is
      affected by variability in positioning and subsequent repositioning of the femur
      for repeated scans. To study the in vitro effect of femoral rotation on the bone
      mineral density (BMD), four fresh-frozen cadaveric femurs were fixed in a
      specially designed jig which allows for rotation of the femurs. BMD measurements
      of the femurs were done in neutral position (0 degrees) i.e., with the femoral
      neck axis parallel to the surface of the couch and at 15 degrees, 30 degrees, and
      45 degrees of internal and external rotation. In vivo precision of the femoral
      neck scan was determined in five normal male subjects. The scans were first done
      with the legs positioned using the manufacturer's foot block. Five scans were
      performed, with repositioning, on the left hip of each subject. The procedure was
      then repeated with the legs positioned using a custom-designed positioning jig to
      minimize the rotation of the hips during a scan. In the in vitro study, the
      femoral neck BMD value was minimum at neutral position (0 degrees) and increased
      when the femur was rotated internally or externally. In vivo precision error of
      the femoral neck scan was reduced by almost 50% with the use of the positioning
      jig when compared with the manufacturer's foot block. Femoral rotation was shown
      to have a significant effect on BMD measurements, and proper positioning of the
      femur during a scan can improve precision significantly.

PMID- 8564798
TI  - 1,25-Dihydroxyvitamin D3 promotes prostaglandin E1-induced differentiation of HL
      60 cells.
AB  - Human promyelocytic HL-60 cells can be induced by biochemical agents to
      differentiate in vitro towards divergent types of myelomonocytic cells. It has
      been reported that prostaglandin E1 (PGE1) can induce granulocytic
      differentiation and that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) can induce
      monocytic differentiation. We have now examined the effects of these compounds,
      both alone and in combination, on HL-60 cell differentiation. PGE1 (1
      microgram/ml) or 1,25(OH)2D3 (10 nM) each inhibited cell proliferation over 48-96
      hours of treatment, but combined treatment with both agents was necessary to
      produce a strong inhibition. The percentage of HL-60 cells that can reduce
      nitroblue tetrazolium (NBT) (a characteristic index of early monocytic or
      granulocytic differentiation) increased 13-fold within 72 hours of PGE1
      treatment, and 1,25(OH)2D3 produced a five-fold stimulation. However, combined
      treatment (PGE1 plus 1,25(OH)2D3) produced a dramatic 35-fold increase. HL-60
      cells did not produce significant levels of nitric oxide (NO) before 48 hours in
      culture, and treatment with PGE1 or 1,25(OH)2D3 did not significantly increase
      cellular NO elaboration over control levels. However, combined treatment produced
      a striking 12-fold increase over control levels. Similarly, combined treatment
      was necessary to obtain the maximal time-dependent stimulation of cellular
      lactate dehydrogenase (LDH) activity (a marker of granulocytic differentiation)
      as well as acid phosphatase (ACP) activity. During this same period of time,
      PGE1, but not 1,25(OH)2D3, markedly stimulated cellular elaboration of
      interleukin (IL)-1 alpha, IL-6, and tumor necrosis factor (TNF)-alpha, and
      1,25(OH)2D3 cotreatment strongly augmented these effects. Thus, combined
      treatment with 1,25(OH)2D3 plus PGE1 generally augmented the apparent conversion
      of these cells, producing synergistic (multiplicative) or additive effects.
      Furthermore, PGE1 induced within 48 hours the more general phenotypic changes
      classically associated with the differentiation of these cells: increased
      expression of chloroacetate esterase (ChAE) (a granulocytic marker), decreases in
      the nuclear/cytoplasmic ratio (characteristic of development beyond the
      promyelocyte/myelocyte stage), and major alterations in morphology from floating
      spherical cells to loosely adherent, elliptical polygons. 1,25(OH)2D3 had little
      effect itself on most of these parameters, but augmented the morphological
      changes induced by PGE1 treatment. Within 48 hours, the ability of these cells to
      reduce the tetrazolium salt WST-1, a general measure of cellular metabolic
      activity, was increased by PGE1, but not by 1,25(OH)2D3; however, the combination
      of 1,25(OH)2D3 and PGE1 again produced the strongest stimulation. Similarly, only
      PGE1 significantly reduced intracellular ATP levels, but combined treatments
      produced a more pronounced decrease. In summary, our findings suggest that PGE1,
      not 1,25(OH)2D3, is sufficient to promote rapid in vitro differentiation of HL-60
      cells along the granulocyte pathway; however, the PGE1-induced conversion of
      these cells is markedly augmented by cotreatment with 1,25(OH)2D3. In addition,
      these converted HL-60 cells preferentially utilize the glycolytic pathway, rather
      than the citric acid cycle, for production of ATP, a metabolic characteristic
      that resembles that described for mature granulocytes.

PMID- 8564799
TI  - Downregulation of colony-stimulating factor-1 (CSF-1) binding by CSF-1 in
      isolated osteoclasts.
AB  - Colony-stimulating factor-1 (CSF-1), also called macrophage colony-stimulating
      factor, is the growth factor for the cells of the mononuclear phagocytic system.
      Furthermore, CSF-1 is essential in osteoclastogenesis and also affects mature
      osteoclasts. The receptor for CSF-1 was demonstrated on cells of the osteoclast
      lineage, with highest levels on the mature cells. This study investigated whether
      the binding of CSF-1 to isolated rat osteoclasts is modulated by the growth
      factor itself. Exposure of osteoclasts to CSF-1 for 1 hour virtually abolished
      binding of the growth factor. After removal of CSF-1, binding sites were restored
      within 4 hours. This recovery was blocked by cycloheximide, indicating the
      dependence on new protein synthesis for reexpression of receptors on the cell
      surface. The observed downregulation of CSF-1 binding sites might be a mechanism
      to control the effects of the growth factor on mature osteoclasts.

PMID- 8564800
TI  - Phosphate regulates the stability of skeletal alkaline phosphatase activity in
      human osteosarcoma (SaOS-2) cells without equivalent effects on the level of
      skeletal alkaline phosphatase immunoreactive protein.
AB  - Inorganic phosphate (P(i)) can regulate the level of skeletal alkaline
      phosphatase (ALP) activity in human osteoblast-like cells, but not by means of
      changes in transcription or release from the cell surface. The current studies
      were intended to determine whether (1) P(i) affected the inactivation of ALP
      activity in human osteosarcoma (SaOS-2) cells; and (2) P(i)-dependent changes in
      ALP-specific activity were associated with equal, concomitant changes in the
      level of ALP immunoreactive protein. The results of these studies revealed that
      P(i) increased the stability of skeletal ALP activity without equivalent effects
      on the level of ALP immunoreactive protein. An increase in P(i) (from 0 to 1.8
      mmol/liter) caused a time-dependent increase in the amount of skeletal ALP
      activity in the SaOS-2 cells, without a parallel increase in the amount of
      skeletal ALP immunoreactive protein, and a decrease in P(i) (from 1.8 to 0
      mmol/liter) caused a time-dependent decrease in the amount of ALP activity,
      without a significant decrease in the total cellular content of ALP
      immunoreactive protein. Together, these observations suggest that P(i) may alter
      the level of skeletal ALP activity in SaOS-2 cells by inhibiting a process of
      irreversible inactivation that does not effect equal, concomitant changes in the
      level of skeletal ALP immunoreactive protein.

PMID- 8564801
TI  - Purification of nonamelogenin proteins from bovine secretory enamel.
AB  - The developing enamel matrix is composed of two groups of proteins that can be
      generally classified as amelogenins and nonamelogenins. The hydrophobic
      amelogenins represent the majority of the developing enamel matrix proteins,
      whereas nonamelogenins include the more hydrophilic enamelins, proteinases, and
      other minor protein components, which represent a small proportion of the matrix.
      This report describes the purification and partial amino acid sequences of two
      previously unknown proteins isolated from developing bovine enamel. These
      proteins were prepared by extracting bovine secretory stage enamel with low ionic
      strength buffer, followed by ammonium sulfate fractionation. The proteins were
      purified by ion-exchange, affinity, and reversed-phase chromatography. We propose
      to designate the proteins BEgp (a glycoprotein) and BEpa. A partial sequence was
      also obtained from a third protein (BEpb) which was nearly identical to BEpa.
      Antibodies were prepared to a synthetic peptide based on the N-terminal sequence
      of BEpa and subsequent immunoblots of various bovine tissues showed a major
      component of approximately 25 kDa specifically in enamel and ameloblasts. Little
      or no cross-reactivity of the antibody was found to bovine proteins extracted
      from heart, lung, kidney, liver, dental pulp, or bone. Similar analyses of both
      rat secretory stage and maturation stage enamel showed two bands of 28 kDa and 29
      kDa. Immunohistochemical localization in rat incisors, showed specific staining
      of the enamel, secretory granules, and Golgi apparatus in ameloblasts. No
      sequence homology with known proteins could be demonstrated for BEgp or BEpa,
      suggesting that these components of developing enamel are novel tooth-specific
      proteins.

PMID- 8564797
TI  - Mechanotransduction and the functional response of bone to mechanical strain.
AB  - Mechanotransduction plays a crucial role in the physiology of many tissues
      including bone. Mechanical loading can inhibit bone resorption and increase bone
      formation in vivo. In bone, the process of mechanotransduction can be divided
      into four distinct steps: (1) mechanocoupling, (2) biochemical coupling, (3)
      transmission of signal, and (4) effector cell response. In mechanocoupling,
      mechanical loads in vivo cause deformations in bone that stretch bone cells
      within and lining the bone matrix and create fluid movement within the
      canaliculae of bone. Dynamic loading, which is associated with extracellular
      fluid flow and the creation of streaming potentials within bone, is most
      effective for stimulating new bone formation in vivo. Bone cells in vitro are
      stimulated to produce second messengers when exposed to fluid flow or mechanical
      stretch. In biochemical coupling, the possible mechanisms for the coupling of
      cell-level mechanical signals into intracellular biochemical signals include
      force transduction through the integrin-cytoskeleton-nuclear matrix structure,
      stretch-activated cation channels within the cell membrane, G protein-dependent
      pathways, and linkage between the cytoskeleton and the phospholipase C or
      phospholipase A pathways. The tight interaction of each of these pathways would
      suggest that the entire cell is a mechanosensor and there are many different
      pathways available for the transduction of a mechanical signal. In the
      transmission of signal, osteoblasts, osteocytes, and bone lining cells may act as
      sensors of mechanical signals and may communicate the signal through cell
      processes connected by gap junctions. These cells also produce paracrine factors
      that may signal osteoprogenitors to differentiate into osteoblasts and attach to
      the bone surface. Insulin-like growth factors and prostaglandins are possible
      candidates for intermediaries in signal transduction. In the effector cell
      response, the effects of mechanical loading are dependent upon the magnitude,
      duration, and rate of the applied load. Longer duration, lower amplitude loading
      has the same effect on bone formation as loads with short duration and high
      amplitude. Loading must be cyclic to stimulate new bone formation. Aging greatly
      reduces the osteogenic effects of mechanical loading in vivo. Also, some hormones
      may interact with local mechanical signals to change the sensitivity of the
      sensor or effector cells to mechanical load.

PMID- 8564802
TI  - Vitamin D3 analogs and salmon calcitonin partially reverse the development of
      renal osteodystrophy in rats.
AB  - We have previously established an uremic rat model which is suitable for
      investigating the effect of various treatment modalities on the progression of
      renal osteodystrophy [1]. Four months subsequent to 5/6 nephrectomy, animals were
      treated three times a week for 3 months with either vehicle, 1,25
      dihydroxyvitamin D3 [1,25(OH)2D3], 1,25(OH)2D3 + 24,25-dihydroxyvitamin D3
      [24,25(OH)2D3], 1,25(OH)2D3 + calcitonin (CT), or 1,25(OH)2D3 + 24,25(OH)2D3 +
      CT. At termination of the study, clinical chemistry, chemical composition, and
      mechanical properties of femurs, calvarial parathyroid hormone (PTH)-elicited
      adenylate cyclase (AC), and phospholipase C (PL-C) activities, femoral cross
      sectional area, and bone histomorphometry were analyzed. The main findings were
      that 1,25(OH)2D3 +/- 24,25(OH)2D3 treatment enhanced elasticity as well as time
      to fracture at the femoral metaphysis. CT potentiated the increase in elasticity
      obtained by 1,25(OH)2D3 +/- 24,25(OH)2D3 treatment. Only 24,25(OH)2D3
      administration rectified the supernormal PTH-stimulated uremic bone AC, and only
      1,25(OH)2D3 medication normalized the diminished CT-elicited AC. The obliterated
      uremic bone PTH-sensitive PL-C was fully normalized by all drug regimens. Femoral
      shaft inner zone diameter was enhanced by uremia, however, all drug treatments
      normalized it. Ditto effect was registered with either drug treatment on the
      subnormal outer and inner zone widths. Histomorphometrical analyses showed that
      1,25(OH)2D3 administration reduced both eroded and osteoid surfaces. Most
      prominently, adjuvant 24,25(OH)2D3 or CT administration potentiated the
      beneficial effect of 1,25(OH)2D3 on fibrosis and osteomalacia. We assert that
      vitamin D3 treatment markedly reverses the development of renal osteodystrophy,
      and CT potentiates the effect of vitamin D3.

PMID- 8564803
TI  - Growth hormone normalizes vertebral strength in ovariectomized rats.
AB  - Ten-month-old lactating breeders were ovariectomized and kept on a low calcium
      diet. One month after ovariectomy, the rats were dosed once daily for 6 months
      with either a low dose of growth hormone (GH) (0.05 mg), a high dose of GH (1
      mg), estrogen plus gestagen (E-G) [17 beta-estradiol (0.1 mg); norethisterone
      acetate (0.05 mg)], or a combination of GH and E-G. Mechanical competence,
      apparent dry density, apparent ash density and ash concentration were measured in
      the fourth lumbar vertebral body. The reduced mechanical strength, ash density
      and ash concentration found in the vertebral body of ovariectomized animals were
      prevented by the high dose of GH alone, or in combination with E-G. E-G alone
      partly prevented the decline in ash density and ash concentration, but did not
      affect the reduced mechanical strength seen after ovariectomy. Only minor effects
      were observed after treatment with the low dose of GH, alone or in combination
      with E-G. In conclusion this study shows that GH administration prevents the
      decline in mechanical strength and bone mineral density seen in rats after
      ovariectomy.

PMID- 8564804
TI  - A simple spike train decoder inspired by the sampling theorem.
AB  - Reconstructing a time-varying stimulus estimate from a spike train (Bialek's
      "decoding" of a spike train) has become an important way to study neural
      information processing. In this paper, we describe a simple method for
      reconstructing a time-varying current injection signal from the simulated spike
      train it produces. This technique extracts most of the information from the spike
      train, provided that the input signal is appropriately matched to the spike
      generator. To conceptualize this matching, we consider spikes as instantaneous
      "samples" of the somatic current. The Sampling Theorem is then applicable, and it
      suggests that the bandwidth of the injected signal not exceed half the spike
      generator's average firing rate. The average firing rate, in turn, depends on the
      amplitude range and DC bias of the injected signal. We hypothesize that nature
      faces similar problems and constraints when transmitting a time-varying waveform
      from the soma of one neuron to the dendrite of the postsynaptic cell.

PMID- 8564805
TI  - A model of spatial map formation in the hippocampus of the rat.
AB  - Using experimental facts about long-term potentiation (LTP) and hippocampal place
      cells, we model how a spatial map of the environment can be created in the rat
      hippocampus. Sequential firing of place cells during exploration induces, in the
      model, a pattern of LTP between place cells that shifts the location coded by
      their ensemble activity away from the actual location of the animal. These shifts
      provide a navigational map that, in a simulation of the Morris maze, can guide
      the animal toward its goal. The model demonstrates how behaviorally generated
      modifications of synaptic strengths can be read out to affect subsequent
      behavior. Our results also suggest a way that navigational maps can be
      constructed from experimental recordings of hippocampal place cells.

PMID- 8564806
TI  - Inorganic considerations on the function of vanadium in biological systems.

PMID- 8564807
TI  - Interaction of vanadates with biogenic ligands.

PMID- 8564808
TI  - Use of vanadate-induced photocleavage for detecting phosphate binding sites in
      proteins.

PMID- 8564809
TI  - Vanadium-protein interactions.

PMID- 8564810
TI  - Stimulation of enzyme activity by oxovanadium complexes.

PMID- 8564811
TI  - Inhibition of phosphate-metabolizing enzymes by oxovanadium(V) complexes.
AB  - The chemical similarities between vanadate and phosphate combined with the
      ability of vanadate to readily undergo changes in coordination geometry allows
      this ion to strongly influence the function of a large variety of phosphate
      metabolizing enzymes. As transition state analogs, spontaneously formed vanadate
      complexes are potent inhibitors of a number of enzymes, including some
      ribonucleases, mutases, and phosphatases. In addition, vanadate is an effective
      inhibitor of many ATPases, kinases, lyases, and synthases. Vanadate oligomers
      tend to be weaker inhibitors than vanadate but do influence the function of
      dehydrogenases, mutases, aldolases, kinases, and others. Of the oligomers,
      decavanadate is unique in that it seems to bind only in polyphosphate binding
      domains. Peroxovanadate has not yet been well studied but it seems to inhibit
      enzymes that do not utilize a pentacoordinate vanadate in the catalysis cycle.
      Additional detailed studies of vanadate-initiated inhibition of enzymes will
      expand our understanding of the various mechanisms of action of vanadate and its
      derivatives that have been briefly described here and will doubtless provide
      insight into other functions of this unique material.

PMID- 8564812
TI  - Vanadium-dependent haloperoxidases.

PMID- 8564814
TI  - Vanadium in ascidians and the chemistry of tunichromes.

PMID- 8564813
TI  - Vanadium nitrogenases of Azotobacter.

PMID- 8564815
TI  - Solution properties of vanadium(III) with regard to biological systems.

PMID- 8564816
TI  - Vanadium transport in animal systems.

PMID- 8564817
TI  - Vanadium in mammalian physiology and nutrition.

PMID- 8564818
TI  - Vanadium compounds as insulin mimics.
AB  - That vanadium compounds act in an insulin-mimetic fashion both in vitro and in
      vivo has been well established. Both inorganic and organic vanadium compounds
      have been shown to lower plasma glucose levels, increase peripheral glucose
      uptake, improve insulin sensitivity, decrease plasma lipid levels, and normalize
      liver enzyme activities in a variety of animal models of both type I and type II
      diabetes. Vanadium treatment of diabetic animals does not restore plasma insulin
      levels but may spare pancreatic insulin. Elucidation of the mechanism(s) of
      action and potentiation of vanadium's insulin-mimetic effect by appropriate
      ligand binding would seem to be the highest priorities for future investigation.

PMID- 8564819
TI  - Antitumor activity of vanadium compounds.

PMID- 8564820
TI  - Analytical procedures for the determination of vanadium in biological materials.

PMID- 8564822
TI  - Construction and evolution of antibody-phage libraries by DNA shuffling.

PMID- 8564821
TI  - The vanadyl ion: molecular structure of coordinating ligands by electron
      paramagnetic resonance and electron nuclear double resonance spectroscopy.

PMID- 8564823
TI  - Baboon bone marrow transplanted to AIDS patient.

PMID- 8564824
TI  - Xenotransplantation at a crossroads: prevention versus progress.
AB  - The infectious disease risks associated with baboon-to-human transplants may
      represent an insurmountable hurdle in the race to save lives. Yet, public health
      agencies are reluctant to regulate xenotransplantation in spite of those risks.

PMID- 8564825
TI  - Salt, cardiovascular complications...

PMID- 8564826
TI  - Anorexia nervosa, self-starvation and the reward of stress.

PMID- 8564827
TI  - Cells, stress and EMFs.
AB  - Recent research suggests that cells respond to electromagnetic fields in the same
      ways as they do to other environmental stresses.

PMID- 8564828
TI  - Making the connections in nerve regeneration.

PMID- 8564829
TI  - A shot in the arm for cocaine addiction.
AB  - Could immunization against cocaine be a viable prophylaxis for cocaine addiction?

PMID- 8564830
TI  - Deaf and dizzy mice with mutated myosin motors.

PMID- 8564831
TI  - Cardiac performance: growth hormone enters the race.
AB  - It is possible that growth hormone can offer therapeutic benefits for treating
      some forms of heart failure.

PMID- 8564832
TI  - . . . and salt resistance.

PMID- 8564833
TI  - Neuropathology in the Down's syndrome brain.

PMID- 8564834
TI  - Tissue-engineered vascular grafts.

PMID- 8564836
TI  - Defending attacks on statistics.

PMID- 8564835
TI  - Effects of tissue factor induced by oxygen free radicals on coronary flow during
      reperfusion.
AB  - Tissue factor is a transmembrane protein that activates the extrinsic coagulation
      pathway by binding factor VII. Endothelial cells, being in contact with
      circulating blood, do not normally express tissue factor. Here we provide
      evidence that oxygen free radicals induce tissue factor messenger RNA
      transcription and expression of tissue factor procoagulant activity in
      endothelial cells in culture. Isolated, perfused rabbit hearts exposed to
      exogenous oxygen free radicals also showed a marked increase in tissue factor
      activity within the coronary circulation. Furthermore, in ex vivo and in vivo
      hearts subjected to ischemia and reperfusion, a condition associated with a
      production of oxygen free radicals in large amounts, a marked increase in tissue
      factor activity occurred. This phenomenon could be abolished by oxygen radical
      scavengers. This increase in tissue factor activity during postischemic
      reperfusion was accompanied by a significant decrease in coronary flow,
      suggesting that increase in tissue factor activity with the consequent activation
      of the coagulation cascade might impair coronary flow during reperfusion and
      possibly contribute to the occurrence of reperfusion injury.

PMID- 8564837
TI  - A smoking-dependent risk of coronary artery disease associated with a
      polymorphism of the endothelial nitric oxide synthase gene.
AB  - Endothelium-dependent vasodilatation is mediated by release of nitric oxide
      formed by constitutively expressed endothelial nitric oxide synthase (ecNOS). We
      explored the distribution of polymorphism ecNOS4a/b in 549 subjects with, and 153
      without, coronary artery disease in relation to smoking. In current and ex
      cigarette smokers, but not nonsmokers, there was a significant excess of
      homozygotes for the rare ecNOS4a allele in patients with severely stenosed
      arteries, compared with those with no or mild stenosis. This genotype was also
      associated with a history of myocardial infarction. This smoking-dependent excess
      coronary risk in ecNOS4a homozygotes is consistent with predisposition to
      endothelial dysfunction.

PMID- 8564838
TI  - Generation of human T lymphocytes from bone marrow CD34+ cells in vitro.
AB  - Analysis of the events that regulate development of red blood cells or
      granulocytes has led to therapies altering clinical conditions associated with
      anemia or neutropenia. The development of therapeutic approaches to target
      conditions associated with lymphopenia, such as AIDS, has been thwarted by
      limited techniques for studying T-lymphocyte development. We describe an in vitro
      system in which human bone marrow CD34+ cells proliferate, acquire the expression
      of the lymphoid-specific RAG-2 gene and a broad repertoire of rearranged T-cell
      receptor genes, develop the ability to produce T cell-specific interleukin-2 and
      achieve a range of T-cell immunophenotypes. The cells also become susceptible to
      infection with the T-lymphotropic strain of human immunodeficiency virus-1, HIV
      1IIIB. This culture system induces human T lymphopoiesis and may permit further
      analysis of the events regulating human T-lineage differentiation. It provides a
      preclinical model for screening stem cell gene therapies directed toward AIDS.

PMID- 8564839
TI  - Health care costs.

PMID- 8564840
TI  - Health care costs.

PMID- 8564841
TI  - A cornucopia of drug discovery?

PMID- 8564842
TI  - Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed
      dendritic cells.
AB  - In this pilot study, we investigated the ability of autologous dendritic cells
      pulsed ex vivo with tumor-specific idiotype protein to stimulate host antitumor
      immunity when infused as a vaccine. Four patients with follicular B-cell lymphoma
      received a series of three or four infusions of antigen-pulsed dendritic cells
      followed, in each instance, by subcutaneous injections of soluble antigen two
      weeks later. All patients developed measurable antitumor cellular immune
      responses. In addition, clinical responses have been measured with one patient
      experiencing complete tumor regression, a second patient having partial tumor
      regression, and a third patient resolving all evidence of disease as detected by
      a sensitive tumor-specific molecular analysis.

PMID- 8564844
TI  - A cornucopia of drug discovery?

PMID- 8564843
TI  - Insoluble wild-type and protease-resistant mutant prion protein in brains of
      patients with inherited prion disease.
AB  - We studied prion proteins (PrP) in skin and brains of Libyan Jews carrying the
      E200K mutation who died of familial Creutzfeldt-Jakob disease (CJD).
      Unexpectedly, studies with brain showed that PrP molecules encoded both by the
      wild-type (wt) and mutant alleles exhibit altered properties characteristic of
      the prion protein associated with prion diseases (PrPSc). Using monospecific
      antisera, we found that wtPrP was insoluble in the brains of three patients who
      were heterozygous for the E200K mutation, whereas mutant PrP was both insoluble
      and protease-resistant. Our results argue that both wild-type and mutant PrP
      undergo conformational changes and are particularly intriguing, because the
      normal isoform PrPc is soluble in nondenaturing detergents and is readily
      digested by proteases, whereas PrPSc is insoluble and resistant to proteolytic
      digestion. Our findings indicate that insoluble wtPrP represents a conformational
      intermediate, the first to be identified, within a pathway in which PrPc is
      converted to PrPSc.

PMID- 8564845
TI  - Grafted cerebellar cells in a mouse model of hereditary ataxia express IGF-I
      system genes and partially restore behavioral function.
AB  - Fetal grafts of normal cerebellar tissue were implanted into the cerebellum of
      Purkinje cell degeneration mutant mice (pcd/pcd), a model of adult-onset
      recessively inherited cerebello-olivary atrophy, in an attempt at correcting
      their cellular and motor impairment. Donor cerebellar cells engrafted in the
      appropriate sites, as evidenced by the pattern of expression of insulin-like
      growth factor-I (IGF-I) system genes. Bilateral cerebellar grafts led to an
      improvement of motor behaviors in balance rod tests and in the open field,
      providing evidence for functional integration into the atrophic mouse cerebellum
      and underscoring the potential of neural transplantation for counteracting the
      human cerebellar ataxias.

PMID- 8564846
TI  - Loss of normal p53 function confers sensitization to Taxol by increasing G2/M
      arrest and apoptosis.
AB  - The anticancer agent paclitaxel (Taxol) stabilizes tubulin polymerization
      resulting in arrest in mitosis and apoptotic cell death. Normal human fibroblasts
      depleted of functional p53 by SV40 T antigen or HPV-16 E6, and primary embryo
      fibroblasts from p53 null mice showed seven- to ninefold increased cytotoxicity
      by paclitaxel. Reduced levels of p53 correlated with increased G2/M phase arrest,
      micronucleation, and p53-independent paclitaxel-induced apoptosis. Surviving
      cells with intact p53 progressed through mitosis and transiently accumulated in
      the subsequent G1 phase, coincident with increased p53 and p21cip1,waf1 protein
      levels. These results are in contrast to studies linking p53 loss with resistance
      to DNA damaging anticancer agents.

PMID- 8564847
TI  - Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in
      mice.
AB  - Fas is an apoptosis-signalling cell surface antigen that has been shown to
      trigger cell death upon specific ligand or antibody binding. Treatment of mice
      with an anti-Fas antibody causes fulminant hepatic failure due to massive
      apoptosis. To test a putative protective effect of the anti-apoptotic Bcl-2
      protein, transgenic mice were generated to express the human bcl-2 gene product
      in hepatocytes. Early onset of massive hepatic apoptosis leading to death was
      observed in all nontransgenic mice treated with an anti-Fas antibody. By
      contrast, hepatic apoptosis was delayed and dramatically reduced in transgenic
      animals, yielding a 93% survival rate. These results demonstrate that Bcl-2 is
      able to protect from in vivo Fas-mediated cytotoxicity, and could be of
      significance for preventing fulminant hepatic failure due to viral hepatitis in
      humans.

PMID- 8564848
TI  - Heme oxygenase: a novel target for the modulation of the inflammatory response.
AB  - Chronic inflammatory diseases place a heavy social and economic burden on the
      resources of many nations, but the number of safe and effective treatments is
      limited. To date, the major research effort has concentrated on those mediators
      responsible for the initiation and maintenance of the pathological process. In
      contrast, little attention has been focused on endogenous factors responsible for
      the resolution of the inflammation. Heme oxygenase ((HO); EC 1.14.99.3) is the
      rate-limiting enzyme in the catabolism of heme to biliverdin (which is converted
      to bilirubin by biliverdin reductase), free iron and carbon monoxide (CO). Two
      isoforms of HO have been characterized, the constitutive isoform, HO-2, which is
      the major isoform present under physiological conditions, and the stress-induced
      isoform, HO-1, which has also been classified as heat-shock protein 32K (ref. 1).
      Increases in HO activity have been implicated in tissue protection against
      oxidative stress. In this communication, we describe the effects of modulating HO
      during an acute complement-dependent inflammatory response. Elevation of this
      enzyme resulted in a striking suppression, whereas inhibition of the enzyme led
      to a potentiation of the inflammatory response. Such novel enzyme modulation has
      application on the one hand to the treatment of inflammatory diseases and on the
      other hand to immnosuppressed states in which the impaired ability to mount an
      adequate inflammatory response may result in death from opportunistic infections.

PMID- 8564849
TI  - HIV summit is a good show.

PMID- 8564850
TI  - Autocrine angiogenic vascular prosthesis with bone marrow transplantation.
AB  - Synthetic vascular prostheses are foreign bodies, so that blood coagulation can
      occur on their luminal surfaces, causing graft occlusion very frequently in
      prostheses of small diameter. A vascular prosthesis needs angiogenesis for
      endothelialization of the luminal surface, as endothelial cells have natural and
      permanent antithrombogenic properties. To induce capillary growth into the graft,
      we developed a method of transplanting bone marrow cells, which are primitive,
      strong enough to survive, and create blood cells, resulting in the inducement of
      capillary growth. In an animal experiment, marrow cells were infiltrated into the
      walls of long-fibril expanded polytetrafluoroethylene (ePTFE) vascular grafts.
      The grafts were implanted in the abdominal aortic position of 24 dogs
      autologously. Marrow cells survived and continued exogenous hemopoiesis for up to
      six months and were immunohistochemically reactive to basic fibroblast growth
      factor (bFGF). All the grafts older than three weeks had complete
      endothelialization and maintained their patency. Twenty grafts without bone
      marrow were implanted as controls. Endothelialization was present at anastomotic
      sites, but other areas were covered with fresh thrombi. Four out of seven control
      grafts were patent with endothelial cell lining at six months, but three were
      occluded and one of the four grafts was still covered with a thrombus layer. Bone
      marrow with its unique native properties produced autocrine angiogenicity in the
      graft.

PMID- 8564852
TI  - Re: QSAR models for predicting the acute toxicity of selected organic chemicals
      with diverse structures to aquatic non-vertebrates and humans. Calleja, M.C.,
      Geladi, P., and Persoone, G. SAR QSAR Environ. Res. 2, 193-234.

PMID- 8564851
TI  - Presence of soluble amyloid beta-peptide precedes amyloid plaque formation in
      Down's syndrome.
AB  - Abnormal and excessive accumulation of the amyloid beta-peptide (A beta) in the
      brain is a major and common characteristic of all Alzheimer's disease (AD) forms
      irrespective of their genetic background. Insoluble aggregates of A beta are
      identified as amyloid plaques. These deposits are thought to form when the amount
      of A beta is increased in the brain parenchyma as a result of either
      overexpression or altered processing of the amyloid precursor protein (APP).
      Soluble A beta ending at carboxyl-terminal residue 40 (A beta 40) and, in lesser
      amount, the form ending at residue 42 (A beta 42), are normal products of the APP
      metabolism in cell cultures. Increased secretion of soluble A beta 42 has been
      observed in cells transfected with constructs modeling APP gene mutations of
      familial forms of AD (refs 4, 5). On the basis of these in vitro data it has been
      hypothesized that the presence of soluble A beta 42 plays a role in the formation
      of amyloid plaques. Subjects affected by Down's syndrome (DS) have an increased
      APP gene dosage and overexpress APP. Apparently because of this overexpression,
      they almost invariably develop amyloid deposits after the age of 30 years,
      although they are free of them at earlier ages. Moreover, it has been observed
      that A beta 42 precedes A beta 40 in the course of amyloid deposition in DS
      brain. Thus, DS subjects provide the opportunity to investigate in the human
      brain the metabolic conditions that precede the formation of the amyloid
      deposits. Here we report that soluble A beta 42 is present in the brains of DS
      affected subjects aged from 21 gestational weeks to 61 years but it is
      undetectable in age-matched controls. It is argued that overexpression of APP
      leads specifically to A beta 42 increase and that the presence of the soluble A
      beta 42 is causally related to plaque formation in DS and, likely, in AD brains.

PMID- 8564853
TI  - Experiences with the application of QSAR in the routine of the notification
      procedure.
AB  - On behalf of the Umweltbundesamt the Fraunhofer Gesellschaft has developed a
      software system (SAR-system) comprising more than 90 estimation models for
      endpoints relevant in environmental risk assessment. These estimation models are
      based on the approach of quantitative structure-activity relationships (QSAR).
      All models were checked for their validity and application range. In the last
      months the Umweltbundesamt started to test the applicability of some models
      concerning the endpoints fish acute toxicity, daphnia acute toxicity and ready
      (i.e., ultimate) biodegradability in the daily routine of the notification
      procedure. For testing these models the corresponding confidential data given in
      the dossiers of substances notified 1993 in Germany, were used. We were able to
      make calculations for 36% of the notified substances. For the remaining 64% of
      the chemicals it was impossible to accomplish SAR estimations due to several
      reasons, e.g., ionic structure of the compounds. Different results for the
      applicability of the mentioned endpoints are obtained. The predictions of the
      fish and Daphnia toxicity are in sufficient agreement with the experimental
      results, in case of the fish toxicity we receive 58% agreement, for the Daphnia
      toxicity 56%. The corresponding values which were obtained in the US EPA/E.C.
      Joint Project on the evaluation of (quantitative) structure activity
      relationships were 82.3% and 70.9%. About 300 different models were used for the
      calculations of these endpoints within the framework of the EPA/EC project. The
      SAR-system presented here contains 8 models for estimating the fish toxicity and
      6 models for the Daphnia toxicity. For the prediction of the biodegradability the
      results obtained with the SAR-system are rather poor and have to be improved.
      Meanwhile the SAR-system is commercially available and can be ordered at the
      Fraunhofer Institute for Environmental Chemistry and Ecotoxicology, Schmallenberg
      (Germany).

PMID- 8564854
TI  - U.S. EPA regulatory perspectives on the use of QSAR for new and existing chemical
      evaluations.
AB  - As testing is not required, ecotoxicity or fate data are available for
      approximately 5% of the approximately 2,300 new chemicals/year (26,000 + total)
      submitted to the US-EPA. The EPA's Office of Pollution Prevention and Toxics
      (OPPT) regulatory program was forced to develop and rely upon QSARs to estimate
      the ecotoxicity and fate of most of the new chemicals evaluated for hazard and
      risk assessment. QSAR methods routinely result in ecotoxicity estimations of
      acute and chronic toxicity to fish, aquatic invertebrates, and algae, and in fate
      estimations of physical/chemical properties, degradation, and bioconcentration.
      The EPA's Toxic Substances Control Act (TSCA) Inventory of existing chemicals
      currently lists over 72,000 chemicals. Most existing chemicals also appear to
      have little or no ecotoxicity or fate data available and the OPPT new chemical
      QSAR methods now provide predictions and cross-checks of test data for the
      regulation of existing chemicals. Examples include the Toxics Release Inventory
      (TRI), the Design for the Environment (DfE), and the OECD/SIDS/HPV Programs. QSAR
      screening of the TSCA Inventory has prioritized thousands of existing chemicals
      for possible regulatory testing of: 1) persistent bioaccumulative chemicals, and
      2) the high ecotoxicity of specific discrete organic chemicals.

PMID- 8564855
TI  - The application of structure-activity relationships (SARs) in the aquatic
      toxicity evaluation of discrete organic chemicals.
AB  - The Office of Pollution Prevention and Toxics (OPPT), United States Environmental
      Protection Agency (USEPA) routinely uses structure-activity relationships (SAR)
      for the aquatic hazard assessment of new chemicals submitted under Section 5 of
      the Toxic Substances Control Act (TSCA). With 15 years of experience and the
      general acceptance of toxicity predictions based on SARs, OPPT has expanded the
      use and application of the methodology to include existing chemicals used in
      printing, dry cleaning, and paint stripping. SAR analysis has also been used in
      the hazard evaluation of the U.S. and EU/OECD high production volume (HPV)
      chemicals. This paper describes the assumptions, limitations, and methodology for
      the use of SARs to evaluate large sets of discrete organic chemicals.

PMID- 8564856
TI  - [The integration of nutrition policies into health plans].

PMID- 8564857
TI  - [The European Alcohol Action Plan. The Alcohol, Drug and Tobacco Unit. Department
      of Lifestyles and Health, Regional Office for Europe. World Health Organization.
      Copenhagen, 1993].
AB  - The translation to the Spanish language of the European Alcohol Action Plan, from
      the Regional Office for Europe of the World Health Organization, is presented as
      a support measure and promotion of its application. The European Alcohol Action
      Plan calls for a European movement to support actions at the local, national and
      international levels. The Action Plan calls for the participation of many
      partners in public, private and voluntary sectors. Its successful implementation
      will make a clearly recognizable contribution to improve Europeans' health and to
      prevent the harm done by the use of alcohol. Alcohol is a major public health
      problem throughout the European Region as a whole. In relation to alcohol, Member
      States hold two shared commitments. The first one is a commitment to the health
      policy for Europe, as expressed in the Targets for Health for All, and
      specifically the target 17 which calls for a 25% reduction in alcohol consumption
      between 1980 and 2000, with particular attention to reduce its harmful use. The
      second one is a commitment to the European Alcohol Action Plan which was strongly
      endorsed at the 1992 Regional Committee as a positive set of guidelines to be
      followed by the European Member States. Member States, nongovernmental
      organizations, the European Union, the Council of Europe and the Nordic Council
      are taking initiatives to reduce the harm produced by the use of alcohol.

PMID- 8564858
TI  - [An agenda to debate: the World Bank report Investing in Health].
AB  - The 1993 World Bank Development Report analyzes the world health situation from
      an economic perspective. In spite of the fact that many of the discussed topics
      are controversial, the report accomplishes an interesting review of different
      health and socioeconomic indicators. The experts of WHO and the World Bank
      elaborated a new measurement of the global burden of disease, the Disability
      Adjusted Life Years (DALYs). It's an indicator that summarizes the health status
      of a population, combining mortality, morbidity and disability data. We think
      that the development of this new indicator is the most novel and positive aspect
      of the report. This indicator stimulates comparisons between countries and
      facilitates decision making processes in the health field. The present work
      summarizes and analyses the most interesting and controversial aspects of the
      World Bank Development Report.

PMID- 8564859
TI  - [The evaluation of the mutagenic activity of public drinking water by the Ames
      test].
AB  - BACKGROUND: The sources of potential mutagens in our environment are many, but
      the most important of these is water for public consumption. This is a result of
      the chlorinating process which is the main reason for the appearance of these
      mutagens. With this in mind, the aim of our study was to check a possible
      mutagenic activity, using the Ames test, in organic concentrates taken from water
      for public consumption in Madrid. METHODS: Several bacterial strains were used,
      namely Salmonella histidine dependent TA1535, TA1538, TA98 and TA100, taken
      originally from Salmonella typhimurium LT2. Each test was performed twice, with
      or without the introduction of the mammalian-microsome activation (S9 mix), as
      per the indications in Ames. The plate incorporation assay was used to test the
      mutagenicity. All samples of the water in question were processed and treated so
      as to create concentrates of organic chlorinated compounds. RESULTS: The highest
      levels of mutagenicity appeared in the TA1535 strain and in the tests where the
      microsome fraction was not used (IM = 1.94). CONCLUSIONS: With regard to
      mutagenic evaluation in organic concentrates taken from water for public
      consumption, no positive activity was found in any of the tester strains.

PMID- 8564861
TI  - [A support intervention for giving up smoking at health centers. A pilot
      experience with trained volunteer therapists].
AB  - BACKGROUND: The work presented describes a descriptive research whose main
      objective was to quantify the degree of interest and participation of health
      service centres in the Valencian Community in a voluntary therapist description
      intervention to support giving up smoking in the workplace. As complementary
      objectives the process was evaluated as well as the effectiveness of the
      multimodal treatment used and the possibilities for improvement. METHOD: The
      proposal of joining the programme was offered by the IVESP who provided a
      specific training course for the volunteers designated by their centres. A
      multimodal program was the method of intervention for smoking cessation. Three
      methods to take back the information (questionnaires, discussion group and delphi
      study) were used. RESULTS: Of the 170 centres contacted from the whole of the
      Regional Ministry for Health and Consumer Affairs, 45% showed a wish to
      participate, 16% designated a monitor to do the training course and 7% carried
      out the treatment in their workplaces; in these centres the average of success
      was 30%. CONCLUSIONS: One of the main conclusions of the study was the difficulty
      to carry out the intervention with volunteers who do not perceive this work as
      part of their occupational obligations as well as the need of detailed planning
      of communication strategies with the centres and the commitment of their
      involvement.

PMID- 8564860
TI  - [The cost-effectiveness of pneumococcal vaccination in Catalonia].
AB  - BACKGROUND: Pneumococcal vaccine is an effective preventive measure against
      pneumococcal infections. Cost-effectiveness of pneumococcal vaccination of 5 or
      more years aged population of Catalonia has been evaluated in this study.
      METHODS: Cost-effectiveness has been estimated in terms of net cost per life-year
      gained (LYG) and net cost per quality adjusted life year gained (QALY). To
      calculate the net program cost, a cost of 1200 pesetas ($ 10) per individual has
      been assumed and averted disease cost in hospital and primary health care have
      been calculated. RESULTS: Pneumococcal vaccination could obtain 3,360 LYGs and
      6,463 QALYs in the population of Catalonia. The program cost has been estimated
      at 2,800 million pesetas. Cost-effectiveness in million pesetas is 10.1 per LYG
      and 4.3 QALY in the age group from 5 to 24; 4.2 per LYG and 1.9 per QALY in the
      age group from 25 to 44; 1.0 per LYG and 0.5 per QALY in the age group from 45 to
      44, and it is negative (benefits > costs) in the age group of 65 years old and
      over. CONCLUSIONS: Pneumococcal vaccination is cost-effective in individuals aged
      65 or more, and has a favourable ratio in those aged from 45 to 64.

PMID- 8564862
TI  - [Dietary knowledge: a comparative study between health professionals and the
      general population].
AB  - BACKGROUND: The aim of the study was to assess physicians knowledge about salt
      and cholesterol content of selected foods, compared with general population
      knowledge. METHODS: A cross-sectional study made in Ciudad Sanitaria y
      Universitaria de Bellvitge (Barcelona). 106 physicians (66% of total) and 71
      students were surveyed voluntarily. The general population sample was chosen from
      Hospital outpatients by systematic random sampling method. RESULTS: A self
      administered questionnaire about salt and cholesterol high or low content of some
      foods demonstrated statistically significant differences (p < 0.001) when the
      average score was compared between health care professionals and the general
      population group, but in many cases right answer percentage did not arise 60
      percent. CONCLUSIONS: Although health care professionals knowledge about salt and
      cholesterol content of diet is higher than among general population, they need a
      better and continuous formation in this issue.

PMID- 8564863
TI  - MRI in thorotrastosis.
AB  - Magnetic resonance imaging (MRI) and computed tomography (CT) were performed in
      four patients with thorotrastosis. On CT scan, Thorotrast (thorium oxide)
      deposition was shown as high-density areas in the liver and spleen and the
      abdominal lymph nodes. These deposits were not found on MRIs. Splenic volume was
      significantly small due to atrophy. The contrast-noise ratio in the spleen on T1
      weighted images was significantly lower. Thorotrast deposition does not affect
      MRI appearance; therefore it may be useful for the early detection of malignant
      tumors as a complication of thorotrastosis.

PMID- 8564864
TI  - Rhabdomyosarcoma of the paranasal sinuses in an adult.

PMID- 8564865
TI  - Computed tomography of hamartoma of the epiglottis.
AB  - We present the computed tomography (CT) findings of a hamartoma of the epiglottis
      occurring in a 58-year-old man. Although hamartomas are particularly uncommon in
      this site. CT identification of fat within the complex mass facilitated diagnosis
      without recourse to an invasive biopsy.

PMID- 8564866
TI  - Dynamic evaluation of swallowing in patients with cerebrovascular accident.
AB  - To determine the specific effects of cerebrovascular accident (CVA) on
      deglutition, especially relative to the site of CVA, we studied videotapes of
      barium swallow examinations in 74 patients who had had a CVA. Although there was
      no distinct correlation between the prevalence of oral and pharyngeal dysfunction
      and the site of CVA, left CVA was prone to impair only the oral phase, and right
      CVA tended to impair both phases.

PMID- 8564867
TI  - CT findings of regression in intraabdominal desmoplastic small-cell tumor.
AB  - We report the computed tomographic (CT) findings in a patient with intraabdominal
      desmoplastic small-cell tumor before and after 10 weeks of chemotherapy. This
      tumor is a rare, frequently fatal neoplasm of the peritoneum, seen predominantly
      in young males. Initial CT demonstrated large intraperitoneal masses, hepatic
      metastases, retroperitoneal and right axillary lymphadenopathy, ascites, and
      pleural effusion. Follow-up CT showed marked decrease of the main tumor bulk and
      complete regression in the axillary nodes.

PMID- 8564868
TI  - Colorectal carcinoma: evaluation with ultrafast CT.
AB  - We investigated the value of ultrafast computed tomography for the preoperative
      assessment of colorectal carcinoma. Ultrafast CT demonstrated the primary tumor
      in 25 (89%) of 28 patients. Local tumor extension was detected with a sensitivity
      of 90%, a specificity of 78%, and an overall accuracy of 82%. Invasion into
      adjacent organs was detected with a sensitivity of 80%, a specificity of 91%, and
      an overall accuracy of 89%. Diagnoses of pericolic or perirectal lymph node
      metastasis were true-positive in ten, true-negative in 12, false-positive in one,
      and false-negative in two and those for distant lymph node metastasis were true
      positive in four, true-negative in 24, and false-negative in one. Ultrafast CT
      may be more useful than conventional CT in evaluating local extension and
      pericolic or perirectal lymph node metastases because it avoids motion artifact.

PMID- 8564869
TI  - Multiplanar display of spiral CT data of the pulmonary hila in patients with lung
      cancer. Preliminary observations.
AB  - Spiral or helical computed tomography (CT)-generated multiplanar reconstructions
      were used in the radiological assessment of the pulmonary hila in patients with
      central lung cancer. Twelve patients with non-small-cell lung cancer and hilar
      abnormalities were examined with contrast-enhanced spiral CT. Studies were
      performed on a Siemens Somatom S or Plus-S scanner using either a 24- or 32
      second spiral. The study volume was from the arch of the aorta to the inferior
      pulmonary veins done in a single breath-hold, using 4-mm collimation, and
      reconstructed at 2-mm intervals. We assessed the quality of vascular enhancement
      and of multiplanar reconstructions. Bronchoscopic, surgical, and pathological
      findings were correlated. Excellent vascular opacification and good-quality
      reconstructions were obtained in all patients. No interscan motion was detected.
      No problems were encountered with the breathholding technique or in the
      reconstruction of images, even in patients with poor respiratory function.
      Multiplanar reconstructions were useful for the evaluation of mediastinal
      including vascular and airways invasion, for optimal definition of lymph node
      groups, for the planning of bronchoscopically guided biopsy, as well as for
      endobronchoscopic laser coagulation therapy and surgical treatment. Spiral CT
      generated multiplanar reconstructions of the hila are helpful for staging,
      solving problems, guiding bronchoscopy, and planning surgery. Even patients with
      limited respiratory reserve can successfully complete the examination.

PMID- 8564870
TI  - Asymptomatic sacroiliitis in inflammatory bowel disease. Assessment by computed
      tomography.
AB  - Plain film radiographs and computed tomography scans of sacroiliac joints in 65
      asymptomatic patients with known inflammatory bowel disease were performed and
      evaluated by two radiologists. Computed tomography revealed the presence of
      asymptomatic sacroiliitis in 21 (32%) of the 65 patients (New York grades 2 to
      4); asymptomatic sacroiliitis was identified by plain film radiography in only 10
      (18%) of 57 patients (p < 0.001). No correlation was observed between the
      presence or absence of sacroiliitis, and the age and sex of patients, disease
      type, or duration of disease. The prevalence and diagnostic value of computed
      tomography in the detection of asymptomatic sacroiliitis in patients with
      inflammatory bowel disease are discussed.

PMID- 8564871
TI  - Magnetic resonance imaging of muscle injury.
AB  - To further evaluate the role of magnetic resonance (MR) imaging in diagnosing and
      managing muscle injuries, eight patients with muscle pain or palpable masses were
      imaged. MR findings were correlated with clinical follow-up data. Increased
      signal was noted on T2-weighted images in torn and overused muscles. One
      extensively scarred muscle required surgical biopsy to exclude a fibrous tumor.
      Three partial muscle tears were treated conservatively. One complete
      musculotendinous junction tear required tendon transfer. MR studies noninvasively
      identified and staged various muscle injuries, thereby influencing management.

PMID- 8564872
TI  - Diastematomyelia in adults. Modern imaging and operative treatment.
AB  - Diastematomyelia, an uncommon dysraphic state usually seen in children, is a
      rarity in adults; only 19 reports have been published in the literature so far.
      Two cases of diastematomyelia in adults are presented and the relevant literature
      is reviewed. Both of these were investigated by computed tomography and magnetic
      resonance imaging. These two procedures are proved to be complementary to each
      other in understanding this anomaly. Both patients exhibited associated
      congenital abnormalities of the neuroectoderm in the form of hyperpigmentation,
      hypertrichosis, lipomatosis, and dermal sinus that were demonstrated with clarity
      by the neuroimaging modalities used. Operative correlation was performed in both
      patients, where findings correlated very well with the preoperative radiological
      evaluation.

PMID- 8564873
TI  - Osteochondroma of the cervical spine. MR findings.
AB  - We report two cases of osteochondroma in the region of the cervical spine. The
      magnetic resonance (MR) images well demonstrated the relationship of the tumor,
      the spinal cord, and adjacent soft tissue, but correct diagnosis by MR imaging
      was difficult in one patient due to unusual gadolinium enhancement. Computed
      tomography played an important role in these patients by demonstrating the exact
      origin and nature of the tumor.

PMID- 8564874
TI  - Interactive multiplanar reformation of conventional two-dimensional MR images.
AB  - In this report, we describe a new application for three-dimensional computer
      image processing that can provide for improved depiction of anatomical structures
      on routine nonvolumetric magnetic resonance (MR) examinations. The technique can
      be applied to standard two-dimensional MR images of the brain, spine,
      musculoskeletal system, and body including those obtained with relatively thick
      slices and with an intersection gap. This report demonstrates use of the
      reformation technique to establish retrospectively the symmetry in bilateral
      structures that were displayed out of alignment due to suboptimal patient
      positioning or patient motion during image acquisition and to improve the
      depiction of anatomical structures that were oriented out of the plane of
      original image acquisition. This method can be performed interactively in near
      real time, requires no increase in patient examination time, and has potential
      application throughout the body.

PMID- 8564875
TI  - An 81-year-old woman with a cystic pancreatic mass.

PMID- 8564876
TI  - The 1994 Upjohn Award Lecture. Molecular and genetic approaches to the study of
      signal transduction in the adrenal cortex.
AB  - This review highlights contributions from my laboratory in which the sites and
      mechanisms of action of the adrenocorticotropic hormone (ACTH) in the adrenal
      cortex have been explored. Early studies showing that ACTH stimulates adrenal
      steroidogenesis by interacting with specific receptors at the cell surface are
      summarized. Next, the development of a strategy of genetic analysis to define the
      signalling events that follow ACTH interaction with its receptor is described.
      This strategy involved the isolation and characterization of mutant adrenal cell
      lines harboring specific defects in the ACTH-responsive steroidogenic pathway. I
      describe the isolation and characterization of several of these mutants and
      demonstrate how these mutants have helped to establish obligatory roles for
      adenylyl cyclase, cyclic AMP (cAMP), and cAMP-dependent protein kinase in the
      steroidogenic actions of ACTH. Finally, some of our studies on the regulated
      expression of the steroidogenic cytochrome P450 enzymes in Y1 adrenal cells are
      reviewed. These latter studies have led to the discovery of a novel promoter
      element and transcription factor (designated steroidogenic factor 1) that
      participates in the coordinate expression of these cytochrome P450 enzymes and
      that is required for their regulated expression by ACTH and cAMP.

PMID- 8564877
TI  - Resistance of the failing dystrophic hamster heart to the cardioprotective
      effects of diltiazem and clentiazem: evidence of coronary vascular dysfunctions.
AB  - Although hypothermia and cardioplegic cardiac arrest provide effective protection
      during cardiac surgery, ischemia of long duration, poor preoperative myocardial
      function, and ventricular hypertrophy may lead to heterogeneous delivery of
      cardioplegic solutions, incomplete protection, and impaired postischemic
      recovery. Calcium antagonists are potent cardioprotective agents, but their
      efficacy in the presence of cold cardioplegia is still controversial, especially
      in heart failure, since it is often believed that failing hearts are more
      sensitive to their negative inotropic and chronotropic actions. However, recent
      data have demonstrated that the benzothiazepine-like calcium antagonists
      diltiazem and clentiazem, in selected dose ranges, elicit significant
      cardioprotection independently of intrinsic cardiodepression, thus lending
      support to their use in cardioprotective maneuvers involving the failing heart.
      We therefore evaluated the cardioprotective interaction of diltiazem, clentiazem,
      and cold cardioplegia in both normal and failing ischemic hearts. Hearts were
      excised from 200- to 225-day-old cardiomyopathic hamsters (CMHs) of the UM-X7.1
      line and age-matched normal healthy controls. Ex vivo perfusion was performed at
      a constant pressure (140 cmH2O; 1 cmH2O = 98.1 Pa) according to the method of
      Langendorff. Heart rate, left ventricular developed pressure (LVDP), and coronary
      flow were monitored throughout the study. Global ischemia was produced for 90 min
      by shutting down the perfusate flow, followed by reperfusion for 30 min. Normal
      and failing CMH hearts were either untreated (control) or perfused at the onset
      of global ischemia with one of the following combinations: cold cardioplegia
      alone (St. Thomas' Hospital cardioplegic solution, 4 degrees C, infused for 2
      min), cold cardioplegia + 10 nM diltiazem, or cold cardioplegia + 10 nM
      clentiazem. The cardiac and coronary dilator properties of 10 nM diltiazem and 10
      nM clentiazem alone were investigated in separate groups of isolated
      preparations. Failing CMH hearts had lower basal LVDP (42 +/- 2 vs. 77 +/- 2 mmHg
      (1 mmHg = 133.3 Pa) for normal hearts, p < 0.05), while coronary flow was only
      slightly reduced (5.6 +/- 0.2 vs. 6.2 +/- 0.2 mL/min for normal hearts).
      Following 90 min global ischemia, coronary flow was increased in both groups, but
      the peak hyperemic response declined only in failing CMH hearts (+50 +/- 17 vs.
      +82 +/- 17% in normal hearts). In normal hearts, LVDP virtually recovered within
      5 min of reperfusion but steadily decreased thereafter (-37 +/- 4% at 30 min). In
      contrast, in failing CMH hearts, LVDP significantly decreased early during
      reperfusion but improved over time (-19 +/- 7% at 30 min). In normal hearts, the
      addition of diltiazem or clentiazem to cold cardioplegic solutions resulted in
      improved postischemic contractile function for the duration of reperfusion (85 +/
      4% vs. only 71 +/- 6% for cardioplegia, p < 0.05). The post-ischemic increase in
      coronary flow was similar in all groups. In failing CMH hearts, the addition of
      diltiazem or clentiazem afforded no significant contractile benefit at
      reperfusion. In nonischemic normal hearts, infusion of diltiazem or clentiazem
      (10 nM) alone increased coronary flow (+6 +/- 1% for diltiazem and +24 +/- 3% for
      clentiazem) without significant negative inotropic or chronotropic effects. In
      nonischemic failing CMH hearts, infusion of diltiazem or clentiazem did not
      elicit cardiodepression. In contrast their coronary dilator actions reverted to
      vasoconstriction (diltiazem) or were significantly attenuated (clentiazem). From
      these experiments we can conclude that, compared with the normal heart, the
      failing CMH heart adapted differently to global ischemia.

PMID- 8564878
TI  - Comparative study of sodium nitroprusside induced vasodilation of human placental
      veins from premature and full-term normotensive and preeclamptic pregnancy.
AB  - The objective of this study was to determine whether nitrovasodilator (nitric
      oxide donor) drug induced relaxation is different between preeclamptic and
      normotensive pregnancy. Human placental veins were collected at the time of
      delivery from normotensive (n = 6 premature, n = 6 full term) and preeclamptic (n
      = 6 premature, n = 3 full term) women and cut into rings. Cumulative
      concentration-response curves were performed on 5-hydroxytryptamine-contracted
      rings for the nitrovasodilator agent, sodium nitroprusside (SNP). The EC50 values
      were determined from the SNP concentration-response curves of the individual
      subjects, and were compared across gestational age and between preeclamptic and
      normotensive pregnancy by two-way ANOVA. There was no difference in the SNP EC50
      values for normotensive and preeclamptic human placental veins in either the
      premature or full-term study groups. However, for both normotensive and
      preeclamptic pregnancy, the SNP EC50 value for full-term placental vein was
      greater than that for premature tissue. The sensitivity of human placental veins
      to SNP is similar between preeclamptic and normotensive pregnancy at similar
      gestational ages, but is increased in premature compared with full-term pregnancy
      in both preeclamptic and normotensive pregnant women.

PMID- 8564879
TI  - In vivo murine studies on the biochemical mechanism of acetaminophen
      cataractogenicity.
AB  - C57BL/6 and DBA/2 mice are, respectively, susceptible and resistant both to the
      induction of aryl hydrocarbon hydroxylase (cytochrome P450 1A1, or CYP1A1) and to
      the cataractogenicity of acetaminophen, which may involve its bioactivation to a
      toxic reactive intermediate, catalysed by P450 and (or) prostaglandin H synthase
      (PHS). Following induction of P450 using beta-naphthoflavone, the
      cataractogenicity of acetaminophen (400 mg/kg ip) in C57BL/6 mice was reduced by
      pretreatment with the P450 inhibitors SKF 525A and metyrapone, the glutathione
      precursor N-acetylcysteine, the antioxidant vitamin E, and the free radical spin
      trapping agent alpha-phenyl-N-t-butylnitrone (p < 0.05). Acetaminophen (200
      mg/kg) cataractogenicity was enhanced by pretreatment with the glutathione
      depletor diethyl maleate (DEM) and the gamma-glutamylcysteine synthetase
      inhibitor buthionine sulfoximine (BSO) (p < 0.05). No significant effect on
      acetaminophen cataractogenicity was observed using the PHS cyclooxygenase
      inhibitors aspirin or naproxen, or the glutathione reductase inhibitor 1,3-bis(2
      chloroethyl)-1-nitrosourea (BCNU). Accordingly, acetaminophen cataractogenicity
      in C57BL/6 mice does not appear to be dependent upon bioactivation by PHS. In
      DBA/2 mice treated with beta-naphthoflavone, a high dose of acetaminophen (750
      mg/kg ip) was not cataractogenic, even after pretreatment with DEM, BSO, or BCNU.
      The resistance of DBA/2 mice to acetaminophen cataractogenesis, despite
      concomitant pretreatments with an inducer of P450 and several agents that
      interfere with glutathione-dependent detoxifying pathways, suggests differences
      in this strain involving cytoprotective pathways subsequent to acetaminophen
      bioactivation and detoxification of the cataractogenic reactive intermediate.
      These results indicate that acetaminophen cataractogenicity in C57BL/6 mice
      results from P450-catalysed bioactivation of acetaminophen to a reactive
      intermediate, possibly a benzoquinone imine and (or) a free radical, the toxicity
      of which is reduced by glutathione-dependent reactions.

PMID- 8564880
TI  - Effect of taurine deficiency on tissue taurine concentrations and pregnancy
      outcome in the rat.
AB  - Taurine status and pregnancy outcome were assessed in rats fed low dietary
      taurine and varying doses of guanidinoethyl sulfonate (GES), a structural
      analogue of taurine. Female Sprague-Dawley rats (225-270 g) were mated overnight
      and assigned to one of four groups from day 0 to 20 of gestation. Taurine
      deficient animals were fed a basal diet containing < 0.001 mumol taurine/g and
      0.5 (n = 7), 1.0 (n = 8), or 2.0% (n = 7) GES in their drinking water, ad
      libitum. Control animals (n = 8) received similar treatment, with 2 mumol
      taurine/g added to the diet and no GES in their water. Taurine was analyzed by
      reverse-phase HPLC, using electrochemical detection after precolumn
      derivatization with ortho-phthalaldehyde. Treatment of rats with varying doses of
      GES produced a sharp decline in maternal liver and brain taurine to 15 and 55% of
      that of control levels, and in fetal liver and brain taurine to 75 and 50% of
      that of control levels, respectively (p = 0.0001; one-way ANOVA). The 2% group
      had a smaller mean (+/- SEM) litter weight than the control group (35.8 +/- 6.1
      vs. 51.9 +/- 2.8 g; p = 0.042) as a result of a smaller litter size. The decrease
      in litter size was associated with confinement of implantation sites to either
      the left or right uterine horn in four of seven dams. Taurine deficiency did not
      result in intrauterine growth retardation or significant external, visceral, or
      skeletal malformations. Developmental defects were not found in any of the
      taurine-deficient groups, but reproductive abnormalities were present at the
      highest dose of the analogue.

PMID- 8564881
TI  - Effect of baroreceptor activation and systemic hypotension on plasma endothelin 1
      and neuropeptide Y.
AB  - To determine whether endothelin (ET-1) and neuropeptide Y (NPY) release are
      controlled by the carotid sinus (CS) baroreceptor or local endothelial
      mechanisms, we isolated and pump perfused the CS in eight chloralose-anesthetized
      dogs and controlled systemic arterial pressure (SAP) with an elevated reservoir
      connected to both femoral arteries. This allowed the SAP to be kept constant
      while CS pressure was varied from 55.8 +/- 2.0 (low CS) to 192 +/- 1.9 (high CS)
      mmHg (1 mmHg = 133.3 Pa) or CS pressure to be kept constant while SAP was lowered
      to 53.9 +/- 1.8 mmHg (low SAP). There was no significant change in ET-1 when CS
      pressure was varied (control, 2.08 +/- 0.50; low CS, 2.18 +/- 0.51; high CS, 2.11
      +/- 0.38 pg/mL), but ET-1 was significantly higher during low SAP (2.93 +/- 0.49
      pg/mL, p < 0.05). This increase was not observed with vagi and CS intact in six
      dogs or with vagi intact and CS constant in four dogs. In contrast, plasma NPY
      was significantly higher in the low CS condition (619.13 +/- 66.87 pg/mL) versus
      high CS condition (528.88 +/- 45.19 pg/mL, p < 0.05) and did not change during
      hypotension. In conclusion, NPY, but not ET-1, is affected by CS baroreceptor
      manipulation, and plasma ET-1 increases in response to hemorrhagic hypotension
      when modulating reflexes are abolished.

PMID- 8564882
TI  - Sulfhydryl involvement in nitric oxide sequestration and nitric oxide induced
      guanylyl cyclase activation in vascular smooth muscle.
AB  - In the present study, the role of vascular smooth muscle sulhydryl groups was
      investigated with respect to sequestration of nitric oxide (NO) and activation of
      soluble guanylyl cyclase by NO. Vascular smooth muscle 100,000 x g supernatant
      (soluble) fraction was prepared in phosphate buffer, using the medial layer of
      bovine pulmonary artery. The soluble fraction was incubated with 100 pmol NO for
      5 min in a sealed flask at 37 degree C under anerobic conditions in the presence
      or absence of the sulfhydryl reagent, N-ethylmaleimide (NEM, 5 mM). NO
      sequestration by the soluble fraction was measured as an indicator of NO binding.
      Total thiol content was measured in the soluble fraction with and without
      exposure to NEM. Guanylyl cyclase activity was measured in the soluble fraction
      with and without exposure to NO and a combination of NO and NEM. NEM decreased
      total thiol content in the soluble fraction from 103.59 nmol/mL to undetectable
      levels, and decreased guanylyl cyclase activity to below basal levels. The
      percentage of NO sequestered by the soluble fraction was inhibited by NEM by
      approximately 25% from a control value of 26.52 +/- 9.39 to 18.72 +/- 8.52, n =
      13, p < 0.05. The data indicate that sulfhydryl groups are essential for guanylyl
      cyclase activation by NO, and are also involved in the sequestration of NO by the
      vascular smooth muscle soluble fraction.

PMID- 8564883
TI  - Thermogenesis during rest and exercise in cold air.
AB  - Nine non-cold-acclimated subjects (5 female, 4 male, mean age 22.5 years) were
      studied to determine whether nonshivering thermogenesis contributes to cold
      induced metabolic heat production during rest (50 min standing) and exercise (40
      min treadmill walking) in 5 degrees C. Propranolol was administered orally
      (females, 60 mg, 1.12 mg.kg-1; males, 80 mg, 0.96 mg.kg-1) to block nonshivering
      thermogenesis. Measurements were taken at both 25 degrees C, 13.1 Torr (water
      vapor pressure; 1 Torr = 133.3 Pa) and 5 degrees C, 3.6 Torr, with sessions
      randomly assigned to be drug-neutral (DN), drug-cold (DC), placebo-neutral (PN),
      and placebo-cold (PC). Body core temperature was not different between any of the
      experimental conditions. Mean body temperature (5 degrees C, 32.2 +/- 0.20
      degrees C (+/- SEM); 25 degrees C, 35.3 +/- 0.20 degrees C) and mean skin
      temperature (5 degrees C, 22.4 +/- 0.70 degrees C; 25 degrees C, 31.4 +/- 0.60
      degrees C) were lower (p < 0.05) in the 5 degrees C than 25 degrees C environment
      (rest, exercise, drug (D), placebo (P), combined); while shivering (EMG) was
      higher (16.5 +/- 3.9% above baseline) at 5 degrees C than 25 degrees C (15 +/-
      2.1% below baseline) (p < 0.05). The greater VO2 in 5 degrees C compared with 25
      degrees C for the same condition is the thermoregulatory VO2 (TVO2). TVO2 (mL.min
      1) was lower (p < 0.05) on the D (mean = 189.5 +/- 17.7) than on the P (mean =
      238.1 +/- 20.2) during rest and during exercise (D, 206.1 +/- 63.7; P, 338.4 +/-
      46.7). The EMG was 21% above baseline in the DC, and 12% above baseline for PC (p
      > 0.05). These results suggest a nonshivering component to heat production during
      acute cold exposure, which can be blocked with propranolol.

PMID- 8564884
TI  - Effects of prolonged low frequency stimulation on skeletal muscle sarcoplasmic
      reticulum.
AB  - The role of prolonged electrical stimulation on sarcoplasmic reticulum (SR) Ca2+
      sequestration measured in vitro and muscle energy status in fast white and red
      skeletal muscle was investigated. Fatigue was induced by 90 min intermittent 10
      Hz stimulation of rat gastrocnemius muscle, which led to reductions (p < 0.05) in
      ATP, creatine phosphate, and glycogen of 16, 55, and 49%, respectively, compared
      with non-stimulated muscle. Stimulation also resulted in increases (p < 0.05) in
      muscle lactate, creatine, Pi, total ADP, total AMP, IMP, and inosine. Calculated
      free ADP (ADPf) and free AMP (AMPf) were elevated 3- and 15-fold, respectively.
      No differences were found in the metabolic response between tissues obtained from
      the white (WG) and red (RG) regions of the gastrocnemius. No significant
      reductions is SR Ca2+ ATPase activity were observed in homogenate (HOM) or a
      crude SR fraction (CM) from WG or RG muscle following exercise. Maximum Ca2+
      uptake in HOM and CM preparations was similar in control (C) and stimulated (St)
      muscles. However, Ca2+ uptake at 400 nM free Ca2+ was significantly reduced in CM
      from RG (0.108 +/- 0.04 to 0.076 +/- 0.02 mumol.mg-1 protein.min-1 in RG - C and
      RG - St, respectively). Collectively, these data suggest that reductions in
      muscle energy status are dissociated from changes in SR Ca2+ ATPase activity in
      vitro but are related to Ca2+ uptake at physiological free [Ca2+ bd in
      fractionated SR from highly oxidative muscle. Dissociation of SR Ca2+ ATPase
      activity from Ca2+ uptake may reflect differences in the mechanisms evaluated by
      these techniques.

PMID- 8564885
TI  - Role of voltage oscillations in the automaticity of sheep cardiac Purkinje
      fibers.
AB  - The role of oscillatory potentials occurring near the threshold for the fast
      sodium current (ThVos) in the induction of spontaneous and repetitive activity
      was studied in sheep Purkinje fibers superfused in vitro. In low extracellular
      potassium concentration, the steepness and amplitude of diastolic depolarization
      increased and ThVos appeared during quiescence. ThVos amplitude increased
      progressively until its depolarizing phase reached the threshold potential for
      the initiation of the action potential. Drive increased the amplitude of
      diastolic depolarization and of ThVos, and longer drives induced faster and
      longer-lasting repetitive activity ("overdrive excitation"). In quiescent fibers,
      barium depolarized the resting membrane and initiated spontaneous discharge
      through ThVos. Acetylcholine had similar actions. Cesium hyperpolarized the
      membrane, thereby suppressing ThVos and related spontaneous activity.
      Tetrodotoxin and lidocaine also suppressed ThVos, but not the driven action
      potentials. In low extracellular potassium plus high extracellular calcium
      concentrations, drive induced ThVos as well as the oscillatory potentials related
      to calcium overload (Vos), but caused overdrive excitation through ThVos, even
      when caffeine was present. We conclude from our results that in Purkinje
      "dominant" pacemaker fibers (i) diastolic depolarization initiates spontaneous
      activity by attaining the threshold for the upstroke of the action potential
      through the depolarizing phase of a ThVos; (ii) the depolarizing phase of ThVos
      is caused by a tetrodotoxin-sensitive Na+ component; (iii) ThVos is voltage
      dependent in that a small depolarization of the resting membrane induces it and a
      small hyperpolarization suppresses it; (iv) ThVos can induce overdrive
      excitation; and (v) ThVos occurs in the absence of calcium overload and has
      distinguishing characteristics from the Vos induced by calcium overload.

PMID- 8564886
TI  - Calsequestrin is essential for the Ca2+ release induced by myotoxin alpha in
      skeletal muscle sarcoplasmic reticulum.
AB  - Myotoxin alpha (MYTX), a polypeptide toxin purified from the venom of prairie
      rattlesnakes (Crotalus viridis viridis), induced Ca2+ release from the heavy
      fraction of skeletal sarcoplasmic reticulum (HSR), using a Ca2+ electrode. The
      effect of MYTX was nearly abolished by pretreatment with ryanodine, an alkaloid
      based Ca2+ channel blocker. In the stopped-flow experiments, MYTX increased the
      choline+ permeability of HSR in the presence of calsequestrin (CS). Single
      channel recording experiments showed that in the presence of CS, the channel
      currents were markedly enhanced by MYTX applied to the cis side, but not to the
      trans side. However, in the absence of CS, MYTX failed to cause the excitatory
      effect in both the experiments. These results suggest that CS is essential for
      MYTX-induced Ca2+ release through the Ca2+ release channels in skeletal HSR.

PMID- 8564887
TI  - Acute effect of prolactin on active calcium absorption in rats.
AB  - Acute effect of prolactin on active calcium absorption was investigated by using
      the in vitro everted gut sac technique. An intraperitoneal administration of a
      pharmacological dose of 0.02 mg prolactin/100 g body weight 5 or 10 min before
      the in vitro experiment significantly increased the active calcium transport
      (represented by the ratio of serosal to mucosal 45Ca concentration) only in the
      duodenum, not in other segments. This prolactin-induced duodenal active transport
      was seen in 8-week-old sexually mature rats but not in 3-week-old weaned, 5-week
      old young, or > 15-month-old rats. Enhanced apical uptake of 45Ca in 2 min by the
      oil-filled everted duodenal sac from rats that received prolactin 5 and 10 min
      prior to the experiment further supported the speculation that prolactin could
      acutely alter the duodenal epithelial handling of calcium.

PMID- 8564888
TI  - Reactive oxygen generation by azomethine H: a new antimalarial drug.
AB  - Superoxide radical (O2-) is a free radical that may be involved in various toxic
      processes. Cu-Zn superoxide dismutase catalyzes the dismutation of the superoxide
      free radical and protects cells from oxidative damage. A rat bioassay validated
      for the identification of the toxic effects of azomethine H revealed increased
      serum activities of amylase, alanine transaminase, and alkaline phosphatase. The
      lipoperoxide and bilirubin concentrations were also increased in animals that
      received azomethine H (1 g/kg) from ascorbic or hydrochloric acid solutions.
      Azomethine H increased Cu-Zn superoxide dismutase activity. This elevation of Cu
      Zn superoxide dismutase activity was highest on the 7th day and was at levels
      comparable with those of control rats from day 60 onwards. Superoxide is an
      important intermediate in the action and toxicity of azomethine H.

PMID- 8564889
TI  - Brain tissue hydrolysate acts on presynaptic adenosine receptors in the rat
      hippocampus.
AB  - Adenosine is a potent inhibitory modulator in the brain. It suppresses
      glutamatergic synaptic transmission and possibly acts as a brain endogenous
      neuroprotective agent. In this study we have examined the effects of a clinically
      used porcine brain tissue hydrolysate, Cerebrolysin, on synaptic transmission in
      the CA1 area of rat hippocampal slices. A major effect of the drug at doses
      approximating those administered clinically to demented patients was a depression
      of synaptic transmission at the Schaffer collateral-commissural pathway in CA1.
      Detailed analysis showed that the inhibition is presynaptic and can be reduced by
      low doses of a specific blocker of adenosine A1 receptors, 8
      cyclopentyltheophylline. Because Cerebrolysin does not contain a detectable
      amount of adenosine, the effect on adenosine A1 receptors must be indirect,
      perhaps by release of the endogenous agonist. This action of Cerebrolysin is
      consistent with a putative neuroprotective action underlying its clinical usage.

PMID- 8564890
TI  - Beta-adrenergic control of renin in sodium-deprived conscious dogs: renal versus
      extrarenal location.
AB  - This study was designed to determine if tonic beta-adrenergic control of plasma
      renin activity (PRA) during dietary sodium restriction is due to stimulation of
      renal beta-adrenoceptors, extrarenal beta-adrenoceptors, or both. Experiments
      were performed in six conscious resting uninephrectomized dogs with chronically
      indwelling catheters in the aorta, vena cava, and remaining renal artery. The
      dogs were fed a low-sodium diet of approximately 7 mequiv. Na/day. PRA decreased
      by 28 +/- 4% of control (p < 0.01) when the beta-adrenoceptor antagonist
      propranolol was infused directly into the renal artery (ira) at a rate of 0.25
      micrograms.kg-1.min-1 for 45 min, whereas iv propranolol infusion at the same
      rate had no effect on PRA. Propranolol infusion, 1 microgram.kg-1.min-1 iv,
      decreased PRA by 22 +/- 8% of control (p < 0.05) and produced significantly
      greater systemic beta-adrenoceptor blockade but a similar renal plasma
      propranolol concentration as with ira infusion, 0.25 micrograms.kg-1.min-1. Thus
      blockade of extrarenal beta-adrenoceptors produced no additional suppression of
      PRA beyond that which could be accounted for by blockade of renal beta
      adrenoceptors. Therefore, suppression of PRA by propranolol is due solely to
      blockade of renal beta-adrenergic receptors in conscious sodium-deprived dogs.

PMID- 8564891
TI  - Detection of functional receptors for the proteinase-activated-receptor-2
      activating polypeptide, SLIGRL-NH2, in rat vascular and gastric smooth muscle.
AB  - We have studied the actions of the proteinase-activated-receptor-2 (PAR2)
      activating polypeptide, SLIGRL-NH2 (SLI-NH2), in rat aorta and in gastric
      longitudinal muscle preparations. In the phenylephrine-precontracted aorta
      preparation, SLI-NH2 caused an endothelium-dependent relaxation that mimicked the
      action of low concentrations (0.5 U/mL) of trypsin and that was blocked by the
      nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester. In
      endothelium-free aorta ring preparation, SLI-NH2 caused neither a relaxation nor
      a contraction. In the gastric longitudinal muscle preparation, SLI-NH2 caused a
      transient contraction that mimicked the action of trypsin (0.5 U/mL) and that was
      sensitive to inhibitors of cyclooxygenase (indomethacin) and tyrosine kinase
      (genistein). Further, using a reverse-transcriptase - polymerase chain reaction
      (RT-PCR) approach we detected, in both assay tissues, mRNA for the rat PAR2
      receptor, and we ascertained, using a cloned receptor cDNA obtained from a rat
      intestinal cDNA library, that the putative N-terminal activating peptide sequence
      of the rat PAR2 receptor (SLIGRL) is identical with the one previously cloned
      from murine tissue. We concluded that, like the thrombin receptor, the PAR2
      receptor may play a pathophysiologic role in the regulation of vascular and
      gastric smooth muscle contractility.

PMID- 8564892
TI  - Length of stay, quality of care and elderly patients.

PMID- 8564893
TI  - Need for GP anesthetists.

PMID- 8564894
TI  - Hereditary prostate cancer.

PMID- 8564895
TI  - Medical researchers in the Slovak Republic seek cooperation with Canadians.

PMID- 8564896
TI  - Kudos for Dr. Balfour Mount.

PMID- 8564897
TI  - Communications security for physicians.

PMID- 8564898
TI  - Physician identifies new syndrome: vaccinator's thumbnail.

PMID- 8564899
TI  - Sex differences among physicians in rural practice.

PMID- 8564900
TI  - Controversies surrounding the administration of vitamin K to newborns: a review.
AB  - OBJECTIVE: To determine (1) the most effective method of administering vitamin K
      to infants to prevent hemorrhagic disease of the newborn (HDNB) and (2) the
      safest method, in light of preliminary evidence suggesting that intramuscular
      administration of vitamin K is associated with childhood cancer. DATA SOURCES: A
      MEDLINE search of articles published between Jan. 1, 1991, and Apr. 30, 1994,
      with the use of MeSH terms "hemorrhagic disease of the newborn", articles were
      limited to those involving human subjects, from birth to adolescence, and to
      articles from journals indexed through Index Medicus and written in English.
      References of all articles found through the initial search, the earliest of
      which was published in 1967, were also reviewed. STUDY SELECTION: Six controlled
      trials met the selection criteria: a minimum 4-week follow-up period, a minimum
      of 60 subjects and a comparison of oral and intramuscular administration or of
      regimens of single and multiple doses taken orally. All retrospective case
      reviews were evaluated. Because of its thoroughness, the authors selected a meta
      analysis of almost all cases involving patients more than 7 days old published
      from 1967 to 1992. Only five studies that concerned safety were found, and all of
      these were reviewed. DATA EXTRACTION: In controlled trials, the risk of HDNB
      caused by vitamin K deficiency among infants receiving different regimens of
      vitamin K; in case studies, method of vitamin K administration and incidence of
      hemorrhagic disease; and in studies concerning safety, odds ratios and relative
      risks of childhood cancer following intramuscular administration of vitamin K.
      DATA SYNTHESIS: Vitamin K (1 mg, administered intramuscularly) is currently the
      most effective method of preventing HDNB. The previously reported relation
      between intramuscular administration of vitamin K and childhood cancer has not
      been substantiated. An oral regimen (three doses of 1 to 2 mg, the first given at
      the first feeding, the second at 2 to 4 weeks and the third at 8 weeks) may be an
      acceptable alternative but needs further testing in large clinical trials.
      CONCLUSION: There is no compelling evidence to alter the current practice of
      administering vitamin K intramuscularly to newborns.

PMID- 8564901
TI  - Appropriateness in health care delivery: definitions, measurement and policy
      implications.
AB  - A major focus of the current health care debate is the notion that a substantial
      proportion of the health care delivered in Canada is inappropriate. There are two
      types of appropriateness: appropriateness of a service and appropriateness of the
      setting in which care is provided (i.e., inpatient v. outpatient or home care).
      Measuring both types objectively requires the comparison of observed patterns of
      care with explicit criteria for appropriate care. The few studies of
      appropriateness conducted in Canada have shown that inappropriate services are
      provided and inappropriate settings are used. Reducing inappropriate health care
      delivery could involve active strategies for the implementation of guidelines and
      better cooperation and coordination within the health care system. However, lower
      rates of health care delivery or even inappropriate health care will not
      necessarily translate into higher quality care or lower costs overall.

PMID- 8564902
TI  - Do consensus conferences influence their participants?
AB  - OBJECTIVE: To determine whether participation in a consensus conference on the
      assessment of dementia would influence conference participants with respect to
      their recommendations to primary care physicians for the assessment of dementia.
      DESIGN: Questionnaire before and after the conference. SETTING: Canadian
      Consensus Conference on the Assessment of Dementia, held in Montreal, Oct. 5 and
      6, 1989. PARTICIPANTS: All 38 experts representing relevant health disciplines
      who participated in the consensus conference; 36 completed both questionnaires.
      OUTCOME MEASURES: Participants' opinion before and after the conference as to how
      frequently each of 28 manoeuvres (12 blood tests, 4 neurologic imaging
      procedures, 4 types of consultation and 8 "other" tests) should be ordered by
      primary care physicians as part of an assessment of a patient with dementia
      suspected in clinical grounds. RESULTS: For 18 (64%) of the 28 manoeuvres (10 of
      the 12 blood tests, 3 of the 4 neurologic imaging procedures and 5 of the 8
      "other" tests), there was a shift in opinion after the conference toward
      recommending that primary care physicians order them less often; for 10 of these
      18 (5 blood tests and 5 "other" tests) the shift was statistically significant.
      For the remaining 10 manoeuvres (36%) the shift in opinion was toward a
      recommendation that primary care physicians order them more often; the shift was
      not statistically significant for any of these 10 manoeuvres. CONCLUSION: Expert
      members of a consensus conference are influenced by the process of having
      participated in such a conference and are capable and willing to chance their
      initial recommendations when confronted with relevant data.

PMID- 8564903
TI  - Access to adult liver transplantation in Canada: a survey and ethical analysis.
AB  - OBJECTIVES: To describe the substantive and procedural criteria used for placing
      patients on the waiting list for liver transplantation and for allocating
      available livers to patients on the waiting list; to identify principal decision
      makers and the main factors limiting liver transplantation in Canada; and to
      examine how closely cadaveric liver allocation resembles theoretic models of
      source allocation. DESIGN: Mailed survey. PARTICIPANTS: Medical directors of all
      seven Canadian adult liver transplantation centres, or their designates. Six of
      the questionnaires were completed. OUTCOME MEASURES: Relative importance of
      substantive and procedural criteria used to place patients in the waiting list
      for liver transplantation and to allocate available livers. Identification of
      principal decision-makers and main limiting factors to adult liver
      transplantation. RESULTS: Alcoholism, drug addiction, HIV positivity, primary
      liver cancer, noncompliance and hepatitis B were the most important criteria that
      had a negative influence on decisions to place patients on the waiting list for
      liver transplantation. Severity of disease and urgency were the most important
      criteria used for selecting patients on the waiting list for transplantation.
      Criteria that were inconsistent across the centres included social support (for
      deciding who is placed on the waiting list) and length of time on the waiting
      list (for deciding who is selected from the list). Although a variety of people
      were reported as being involved in these decisions, virtually all were reported
      to be health to be health care professionals. Thirty-seven patients died while
      waiting for liver transplantation in 1991; the scarcity of cadaveric livers was
      the main limiting factor. CONCLUSIONS: Criteria for resource allocation decisions
      regarding liver transplantation are generally consistent among the centres across
      Canada, although some important inconsistencies remain. Because patients die
      while on the waiting list and because the primary limiting factor is organ
      supply, increased organ acquisition efforts are needed.

PMID- 8564904
TI  - Administration of Vitamin K to newborns: implications and recommendations.
AB  - The review by Drs. Brousson and Klein (see pages 307 to 315 of this issue)
      identifies controversies surrounding the administration of vitamin K to babies
      shortly after birth. Controlled studies comparing the effect of oral and
      intramuscular administration are unlikely to be conducted because of the large
      number of subjects needed. The evidence presented in the review should dispel
      concerns that intramuscular administration may be associated with childhood
      cancer. Oral administration of a single dose of vitamin K soon after is
      associated with significant biochemical vitamin K deficiency by 1 month of age,
      but the relation of biochemical abnormality to clinical manifestations of late
      hemorrhagic disease of the newborn is less clear. Epidemiologic studies indicate
      a small, but significant, increase in the incidence rate of hemorrhagic disease
      after oral administration of vitamin K (1.0 to 6.4 incidents per 1000 000
      infants), compared with the incidence rate after intramuscular administration
      (0.25 incidents per 100 000 infants). Although repeated oral doses of vitamin K
      may be and effective alternative regimen, there is no approved oral vitamin K
      formulation, there are concerns about patient compliance, and there has been
      limited investigation of such regimen. Therefore, intramuscular administration of
      a single dose of 1.0 mg of vitamin K shortly after birth is recommended.

PMID- 8564905
TI  - National guidelines for vaccine storage and transportation. Bureau of
      Communicable Disease Epidemiology.

PMID- 8564906
TI  - The use of oral ganciclovir in the treatment of cytomegalovirus retinitis in
      patients with AIDS.
AB  - OBJECTIVE: To recommend the appropriate use of oral ganciclovir as an alternative
      to intravenous (i.v.) maintenance therapy for cytomegalovirus (CMV) retinitis in
      patients with AIDS. OPTIONS: i.v. infusion of ganciclovir and foscarnet have been
      the only approved choices for maintenance therapy until the introduction of oral
      ganciclovir. OUTCOMES: Ease of administering maintenance therapy and improved
      quality of life for patients with AIDS. VALUES: The medical advisory group
      comprised physicians treating patients with AIDS therapy. Ease of administration
      of maintenance therapy and quality of patients' lives were considered important.
      BENEFITS, HARMS AND COSTS: Oral ganciclovir is a safe and convenient alternative
      to i.v. maintenance therapy for patients with CMV retinitis. However, its low bio
      availability precludes its use for induction therapy and necessitates careful
      monitoring for compliance. Compared with i.v. administration of ganciclovir, oral
      maintenance therapy is cost effective. EVIDENCE: Evidence for the guidelines was
      gathered from data presented at a symposium on CMV retinitis and oral
      ganciclovir, clinical trials of oral ganciclovir and input from a visiting
      expert. It was presented at a meeting of the advisory board whose members are
      involved in the care of patients with AIDS and the management of CMV retinitis.
      The guidelines were approved by each member of the advisory board.
      RECOMMENDATIONS: Diagnosis, treatment and follow-up of CMV retinitis should
      always be in consultation with an ophthalmologist who is experienced in treating
      this disease. The patient should be fully informed about the limitations of the
      oral form of ganciclovir; he or she should be involved in decision making and
      carefully monitored. Oral ganciclovir should not be used for induction therapy or
      for maintenance therapy in high-risk patients. VALIDATION: Similar guidelines
      have been produced in England where the drug has been available since January
      1995. SPONSOR: The deliberations of the advisory board and the preparation of
      this report were funded through an educational grant from Hoffmann-La Roche
      (Canada).

PMID- 8564907
TI  - 45,000 may have been infected with HIV.

PMID- 8564908
TI  - Electromagnetic interference can cause hospital devices to malfunction, McGill
      group warns.
AB  - Electromagnetic interference (EMI) from sources such as television transmitters,
      police radios and cellular phones can cause medical monitors and other hospital
      devices to malfunction, says the principal investigator of a McGill biomedical
      engineering group set up in 1989 to study, predict and prevent such problems. The
      impact of equipment malfunction can range from mere inconvenience to serious
      problems. The research group advises physicians and other health care
      professionals to learn how to spot problems related to EMI and electromagnetic
      compatibility.

PMID- 8564909
TI  - NHS waiting list have been a boon for private medicine in the UK.
AB  - Health care: public, private or both? In Great Britain, about 13% of the
      population is covered by private health insurance, and everyone else is served by
      the public health care system known as the National Health Service, or NHS.
      Caroline Richmond, who examined the impact of private medical practice in
      Britain, says people become private patients for one compelling reason: to avoid
      the NHS's notoriously long waiting lists for surgery. According to Professor Alan
      Maynard, a health care researcher, the mainstays of the private sector are the
      "three h's" --hips, hernias and hemorrhoids-- along with some elective surgery,
      particularly in gynecology and opthalmology. Another small sector focuses on
      fertility regulation and cosmetic surgery. Although the levels are not monitored
      closely, physician consultants are not permitted to earn more than 10% of their
      income from private practice.

PMID- 8564910
TI  - A clinician's experiences on the Internet.
AB  - Dr. John Doyle, a Toronto anesthetist, shares some recent experiences on the
      Internet. He explains how he became involved and how electronic mail and computer
      resources help in his daily clinical practice. He also explains how he and other
      clinicians share opinions, expertise and advice through an Internet-based
      discussion group devoted to his specialty.

PMID- 8564911
TI  - McMaster's pioneer in evidence-based medicine now spreading his message in
      England.
AB  - Dr. David Sackett, formerly of McMaster University and now at Oxford University
      in England, is considered one of the pioneers of the evidence-based medicine
      movement. This article looks at his colleagues' assessment of Sackett's
      contributions to medicine and at Sackett's own views on his lengthy career.

PMID- 8564912
TI  - Concerns of patients, MDs are transforming transfusion medicine.
AB  - Fear of HIV and AIDS has been the driving force in reducing physicians' use of
      blood and blood products. Nancy Robb interviewed doctors across the country to
      determine steps they are taking to lower the number of transfusions and
      discovered that transfusion medicine in Canada has undergone a sea change.

PMID- 8564913
TI  - Informed consent and blood transfusions.

PMID- 8564914
TI  - Understanding schizophrenia: the impact of novel antipsychotics.

PMID- 8564915
TI  - The psychobiology of first-episode schizophrenia.
AB  - OBJECTIVE: To examine research and clinical interest in the first episode of
      schizophrenia. Pathobiological features have been shown to be a consequence of
      the disorder rather than the effects of chronicity, drug treatment or
      institutionalization. There is increasing evidence that ventricular enlargement
      is a robust finding and hypofrontality on PET and SPECT is associated more with
      symptomatology than with neuroleptic treatment. RESULTS: Neuroleptic threshold
      studies suggest that lower daily dosages and onset of medication may be the most
      important response prediction parameters. CONCLUSION: The role of novel
      antipsychotics in the treatment of first-onset schizophrenia merits investigation
      for lower rates of extrapyramidal syndromes and tardive dyskinesia. To reduce
      relapse rates, psychiatrists need to introduce practice standards employing those
      biopsychological features in the management of first-episode schizophrenia.

PMID- 8564916
TI  - Neuroleptic dosing and neuroleptic plasma levels in schizophrenia: determining
      the optimal regimen.
AB  - OBJECTIVE: To recommend dose range and therapeutic plasma concentration for
      several neuroleptics, and to discuss conditions under which neuroleptic plasma
      levels are clinically useful. METHOD: Neuroleptic drug therapy is a major
      component of the acute and maintenance treatment of schizophrenia. However, there
      is no consensus on what constitutes an appropriate or optimal dose of
      antipsychotic drug in individual patients. Low-dose medication has the potential
      to improve psychosocial function and reduces the frequency of side effects but
      can lead to an increase in positive symptoms and schizophrenic relapse. High
      doses may be associated with behavioural toxicity, symptom exacerbation, a
      worsening of secondary deficit symptoms, impaired social functioning and
      increased adverse effects such as acute extrapyramidal symptoms and tardive
      dyskinesia. Numerous clinical studies have attempted to determine the degree of
      correlation between dose, neuroleptic blood levels, and clinical response.
      RESULTS: To date, this approach has met with only limited success: neuroleptic
      dose overall appears to be a poor predictor of clinical outcome, and the
      suggested therapeutic plasma level concentrations of some antipsychotic drugs
      cannot be regarded as established by any means. Furthermore, the ability to
      conduct neuroleptic plasma levels is not readily accessible in the usual clinical
      setting. In the acute treatment phase, titrating the dose until the onset of
      minimal cogwheel rigidity or hypokinesia (neuroleptic threshold dose) has met
      with some success and is preferable to standard dosing as a means of
      individualizing pharmacotherapy. During the maintenance phase, a slow and gradual
      dosage reduction with adjunctive psychosocial and psychotherapeutic intervention
      is the preferred strategy. CONCLUSION: Reinforcing patient and physician
      compliance is a key element in achieving an optimal treatment regimen.

PMID- 8564917
TI  - Tardive dyskinesia: a review.
AB  - OBJECTIVE: To review recent research findings on tardive dyskinesia (TD) with
      relevance to clinical practice. METHOD: TD is a syndrome of involuntary movements
      that can occur in association with chronic neuroleptic use. It is of unknown
      pathophysiology. It can be irreversible, is cosmetically disfiguring, and can be
      functionally disabling. RESULTS: There is as yet no treatment of demonstrated
      efficacy for TD. It is an iatrogenic disorder whose incidence is increased by age
      and total cumulative dose of typical neuroleptics. It has been the source of
      successful litigation in some jurisdictions but, until very recently, there has
      been no effective antipsychotic agent without this effect. CONCLUSION: This
      litigation in some jurisdictions has been a major impetus to the development of
      novel antipsychotic agents. It is less well known that a similar, possibly
      identical, movement disorder occurs spontaneously particularly in the elderly and
      in patients with schizophrenia, and that TD is often reversible.

PMID- 8564918
TI  - Negative symptoms and affective disturbance in schizophrenia and related
      disorders.
AB  - OBJECTIVE: To review the data and discuss clinical recommendations for treating
      negative symptoms of schizophrenia. Negative symptoms (e.g., poverty of thought,
      affective blunting) have been regarded as part of schizophrenia since Kraepelin's
      early descriptions, although they remain a subject of controversy. For example,
      it is unclear if negative symptoms are distinct from other psychiatric symptoms
      such as depression, or are in actuality depression within schizophrenia. Recent
      evidence suggests that negative symptoms are independent of depression. METHOD:
      Factor analytic studies have suggested that a negative factor (loss of affect,
      volition, poverty of thinking) may be distinguished from other components and is
      separable from a depression factor. Experimental use of vignettes have also been
      useful in the assessment of negative symptoms. A second controversial area is
      whether or not the presence or absence of affect is the fundamental issue
      separating schizophrenia from other psychoses. RESULTS: A continuum of psychosis
      has been hypothesized, with unipolar psychotic depression at one pole and
      schizophrenia with defect state at the other. Within this proposed continuum,
      negative symptoms are associated only with schizophrenia without affect and with
      defect state schizophrenia. As such, variation in affect could be a primary
      determinant of the type of psychosis. CONCLUSION: It appears that negative
      symptoms are a distinct aspect of schizophrenia and may aid in our understanding
      of psychotic disorders.

PMID- 8564919
TI  - Economics of schizophrenia.
AB  - OBJECTIVE: To discuss the costs associated with mental illnesses that constitute
      a significant percentage of the total direct health care costs, currently
      estimated at $1605 per person per year (9% of the gross national product). The
      cost of all mental illness in the US has been estimated at US$103.7 billion (1985
      dollars), of which schizophrenia alone accounts for US$22.7 billion. METHOD: A
      number of studies that have attempted to evaluate the cost of therapies in
      schizophrenia are examined. RESULTS: While schizophrenia affects only 1% of the
      population, it accounts for 2.5% of total health care expenditures in the US. For
      first-admission patients suffering from schizophrenia, it would appear to cost
      less to provide the most clinically-effective treatments than to provide a good
      level of milieu care with special treatment. CONCLUSION: Community-based care can
      be less costly than conventional hospital-based programs and can improve patient
      quality of life. Inhospital programs that reduce length of stay with the use of
      medication clinics or day hospital care may achieve significant cost savings. A
      special challenge is the subgroup of patients suffering from schizophrenia that
      is neuroleptic-resistant. New drugs, such as the atypical neuroleptics, clozapine
      and risperidone, may prove to be highly cost-effective in treating schizophrenia
      by preventing relapse and reducing hospital lengths of stay.

PMID- 8564920
TI  - Prevention of doxorubicin induced cardiotoxicity by catechin.
AB  - Doxorubicin (dox) is an anthracycline antibiotic which is broadly used in solid
      tumors. Long-term therapy with this drug is accompanied by potentially lethal,
      dose-dependent side effects. Several reports suggest that oxygen free radicals
      produced during the metabolic activation of dox may have toxic effects on heart
      muscle. We tried to protect dox cardiotoxicity in rats using catechin which is a
      known antioxidant and iron chelating agent. Different dose levels and
      combinations of catechin and doxorubicin have been studied in different
      experimental groups. Electrocardiograms, myocardial contractility, body weight
      and the electron microscope were used to assess the cardioprotective effect of
      catechin in dox-treated animals. We found significant prevention of dox-induced
      cardiotoxicity by catechin in rats.

PMID- 8564921
TI  - Chemosensitization and drug accumulation assays as complementary methods for the
      screening of multidrug resistance reversal agents.
AB  - Two methods based on the reversion of adriamycin-resistance o the increase of
      Rhodamine 123 accumulation in a multidrug resistant (MDR) cell line have been
      simplified and adapted for the screening of MDR reversal agents. Both methods are
      carried out in microtiter plates, are highly sensitive and can be easily
      automated. In both assays verapamil and the cyclosporine derivative PSC 833 could
      be detected at concentrations lower than 1 and 0.05 microM, respectively.
      Depending on the MDR cell line used, drugs exhibiting the collateral sensitivity
      phenomenon can be selected in the cytotoxicity assay, while interferences due to
      sample toxicity are easily avoided in the dye accumulation assay.

PMID- 8564922
TI  - trans,trans-2,4-decadienal: cytotoxicity and effect on glutathione level in human
      erythroleukemia (HEL) cells.
AB  - The effects of trans,trans-2,4-decadienal (DDE), an isomer of a lipid
      peroxidation product were investigated on the human erythroleukemia cell line
      (HEL TIB 180). DDE strongly inhibits cell growth and affects cell viability
      without any differentiating effects. DDE treatment of HEL cells leads to a marked
      variation of the cellular glutathione level (GSH) and is involved in the
      beginning of DNA fragmentation.

PMID- 8564923
TI  - Mutations involving the endogenous ecotropic murine leukemia virus in primary
      mammary carcinomas of BALB/c mice.
AB  - Endogenous murine leukemia virus-related elements (MLVEs) are often overexpressed
      in primary mammary carcinomas of BALB/c mice. We therefore searched for mutations
      associated with MLVEs and found amplified sequences of the ecotropic MLVE in
      hormonally and chemically induced mammary neoplasms. Restriction fragment length
      polymorphism (RFLP) analysis revealed DNA rearrangements consistent with 1-10 or
      more new copies of the ecotropic MLVE in the genome of these tumors. This is the
      first evidence of mutations involving an endogenous retrovirus other than mouse
      mammary tumor virus in mouse mammary carcinomas.

PMID- 8564924
TI  - All-trans beta-carotene enhances mitogenic responses and ornithine decarboxylase
      activity of BALB/c 3T3 fibroblast cells induced by tumor promoter and fetal
      bovine serum but suppresses mutagen-dependent umu C gene expression in Salmonella
      typhimurium (TA 1535/pSK 1002).
AB  - Although previous epidemiological studies have indicated that beta-carotene is an
      important agent for the chemical prevention against carcinogenesis, a recent
      prospective study has strikingly suggested that supplementation with beta
      carotene significantly increased the incidence of some types of cancer (The alpha
      Tocopherol and beta-Carotene Cancer Prevention Study Group, New Engl. J. Med.,
      330 (1994) 1031-1035). To analyze the discrepancy of this problem, the authors
      analyze the effects of beta-carotene on biochemical and biological events
      associated with carcinogenesis by in vitro experiments. (1) All-trans beta
      carotene enhanced the proliferation and DNA synthesis of BALB/c 3T3 cells induced
      by a tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and fetal bovine
      serum, although beta-carotene itself did not show mitogenic activity. (2) All
      trans beta-carotene caused a remarkable stimulation for the early induction of
      ornithine decarboxylase (ODC) activity after the stimulation of TPA and fetal
      bovine serum. (3) All-trans beta-carotene exhibited significant antimutagenic
      activity which suppresses umu C gene expression in Salmonella typhimurium (TA
      1535/pSK 1002) induced by a typical mutagen, 2-aminoanthracene (2-AA). These
      experimental results suggest that all-trans beta-carotene might cause beneficial
      and harmful effects on different phases of carcinogenesis.

PMID- 8564925
TI  - CYP2D6 genotypes in Spanish women with breast cancer.
AB  - Wild type and three mutated alleles of the polymorphic CYP2D6 gene were studied
      in genomic DNA samples from 187 women with breast carcinoma and 151 healthy women
      by a mutation-specific polymerase chain reaction. The prevalence of the enzyme
      inactivating CYP2D6(B) allele was higher among patients (18.2%) than in controls
      (11.6%; OR = 1.7; 95% c.i. = 1.14-3.13; P = 0.018). This excess was more marked
      in postmenopausal patients (19.8%, P = 0.0086) and in patients with non-ductal
      infiltrating carcinomas (25.8%, P = 0.003). The percentage of carriers of only
      one active gene (heterozygote extensive metabolizers) was higher in patients (31%
      vs. 19.9%; OR = 1.81; 95% c.i. = 1.06-3.11; P = 0.02). The CYP2D6(B)-carrier
      state may be related to a greater risk of breast cancer in women.

PMID- 8564926
TI  - N-nitrosamines and their effects on the level of glutathione, glutathione
      reductase and glutathione S-transferase activities in the liver of male mice.
AB  - The present study investigates the influence of different chemical structure of N
      nitroso compounds on the hepatic level of reduced glutathione (GSH), glutathione
      reductase (GSH-R) and glutathione S-transferase (GST) activities in the liver of
      male Balb/C mice after treatment with 20 mg/kg body weight of each compound for 1
      h as a single dose. The level of reduced glutathione decreased significantly
      between 37 and 70% after the treatment of male mice with ethylbutylnitrosamine (
      37%), diphenylnitrosamine (-50%), propylbutylnitrosamine (-52%),
      diethylnitrosamine (-54%), ethylmethylnitrosamine (-55%), and dibutylnitrosamine
      (-70%), whereas, methylpropylnitrosamine increased the level of GSH by 71%. All
      the N-nitrosamine compounds tested increased the activity of glutathione
      reductase except ethylmethylnitrosamine had no effect. The activity of
      glutathione S-transferase activity was inhibited after treatment of the male mice
      with diphenylnitrosamine (-60%), dibutylnitrosamine (-60%), and
      methylpropylnitrosamine (-81%), while, ethylmethylnitrosamine and
      ethylbutylnitrosamine had no effect on such activity. On the other hand,
      diethylnitrosamine increased the activity of glutathione S-transferase by 50%. It
      can be postulated from this study that the chemical structure of N-nitrosamines
      plays a significant role in the alteration of GSH level and GSH metabolizing
      enzymes, since the substitution of different groups on the nitroso group was
      found to be capable of causing an alteration in such activities.

PMID- 8564927
TI  - Expression of heat shock proteins, glutathione peroxidase and catalase in
      childhood acute lymphoblastic leukemia and nephroblastoma.
AB  - In this study we analyzed the mRNA expression of the heat shock proteins 27 and
      70, and the expression of the radical scavenging enzymes catalase and glutathione
      peroxidase (GPX) in childhood acute lymphoblastic leukemia (ALL, n = 54) and in
      nephroblastoma (n = 34). We found a significant positive correlation between both
      heat shock proteins and also between glutathione peroxidase and both heat shock
      proteins in ALL and nephroblastoma. There was also a significant correlation
      between catalase and glutathione peroxidase detectable. Furthermore, we
      investigated whether the expression of the heat shock proteins and the
      antioxidant enzymes glutathione peroxidase and catalase have implications in the
      clinical outcome in ALL. However, we found no significant correlation between the
      expression of these proteins and relapse rate, the relapse free intervals or the
      overall survival.

PMID- 8564928
TI  - The antitumoral compound Kahalalide F acts on cell lysosomes.
AB  - The target for the antitumoral peptidic drug, Kahalalide F, has been studied in
      cultured cells. In the presence of the compound, the cells became impressively
      swollen, showing the formation of large vacuoles. The formation of these vacuoles
      appears to be the consequence of changes in lysosomal membranes. Thus, lysosomes
      are a target for Kahalalide F action.

PMID- 8564929
TI  - Metabolic conversion and growth effects of n-6 and n-3 polyunsaturated fatty
      acids in the T47D breast cancer cell line.
AB  - The incorporation and conversion of polyunsaturated fatty acids (PUFA) of n-3 and
      n-6 families were examined in the T47D breast cancer cell line in parallel with
      their effects on cell proliferation. In low serum-containing medium, PUFA exerted
      differential growth effects, depending both on their affiliation and unsaturation
      degree. The study of PUFA processing suggested that T47D cells are deficient in
      delta 6 and delta 4-desaturation activities whereas they can process to delta 5
      desaturation. Thus, the PUFA growth effect on T47D cells appeared to be
      associated with a lack of desaturation.

PMID- 8564930
TI  - Induction of apoptosis in human lymphocytes treated with Viscum album L. is
      mediated by the mistletoe lectins.
AB  - Viscum album L. (VAL) is a phytopreparation used in adjuvant cancer therapy with
      both immunostimulatory and DNA stabilizing properties at low drug concentrations
      and cytostatic/cytotoxic properties at higher concentrations. The present work
      examines the cytotoxic effects of VAL extracts produced from mistletoes grown on
      different host trees and of purified toxic proteins from VAL, such as the D
      galactose-specific lectin I (ML I), the N-acetyl-D-galactosamine-specific ML II
      and ML III, and crude viscotoxins towards cultured human lymphocytes. The
      decrease in the number of cultured lymphocytes and blast cells treated with whole
      plant extracts from VAL was host tree-specific. Nevertheless, there was no close
      correlation to the content of MLs or viscotoxins. Using the purified proteins, it
      became obvious that the cell killing was mediated by the induction of apoptosis,
      as measured by the appearance of a hypodiploid DNA peak using flow cytometry. ML
      III was the most effective to induce apoptosis, followed by ML II and ML I, while
      the viscotoxins and oligosaccharides from VAL did not. By measuring the surface
      expression of IL-2R alpha chains, transferrin receptors and APO-1/Fas molecules
      on non-apoptotic T cells, no significant changes were observed at low ML
      concentrations (1 ng/ml), but their decrease at higher ones. Our findings suggest
      that there might be at least two different ways of cell killing operative in VAL
      mediated cytotoxicity: (a) the typical apoptotic cell death with the appearance
      of hypo-diploid nuclei, and (b) a direct or indirect killing by damaging the cell
      membrane with subsequent influx of Ca2+ and of the DNA intercalating dye
      propidium iodide and cell shrinkage. These effects might not be exclusive, as
      they probably occur simultaneously.

PMID- 8564931
TI  - Muscle hypercatabolism during cancer cachexia is not reversed by the
      glucocorticoid receptor antagonist RU38486.
AB  - In rats into which a fast growing ascites hepatoma (Yoshida AH-130) had been
      transplanted, tumor growth elicited a marked loss of body weight and tissue
      waste, particularly of the skeletal muscle. This depletion has been associated
      with enhanced rates of protein breakdown, mainly due to hyperactivation of the
      ATP-ubiquitin-dependent proteolytic system [Llovera, M., Garcia-Martinez, C.,
      Agell, N., Marzabal, M., Lopez-Soriano, F.J. and Argiles, J.M. (1994) FEBS Lett.,
      338, 311-318]. Profound alterations of the hormonal status and the production of
      tumor necrosis factor have been involved in the development of such wasting
      syndrome [Tessitore, L., Costelli, P. and Baccino, F.M. (1993) Br. J. Cancer, 67,
      15-23]. In the present study, the role of glucocorticoids in muscle
      hypercatabolism was investigated using the glucocorticoid receptor antagonist
      RU38486. The treatment with this drug was unable to interfere with the
      development of cachexia in the AH-130 hosts with regard to tissue weight as well
      as to muscle protein turnover rates. As one would expect, the RU38486 was also
      ineffective in lowering both the expression of ubiquitin mRNA and the degree of
      muscle protein ubiquitinization in AH-130 bearers. These data allow us to exclude
      that glucocorticoids play a direct crucial role in the development of cachexia in
      this tumor model.

PMID- 8564932
TI  - Chemosensitizing interactions of clofazimine and B669 with human K562
      erythroleukaemia cells with varying levels of expression of P-glycoprotein.
AB  - Differential expression of a permeability glycoprotein (P-gp) in human
      myeloleukaemia K562 cells grown in the presence of the anti-cancer drug,
      doxorubicin, gave rise to subclones with varying degrees of resistance to other
      anti-tumour drugs such as vinblastine and daunorubicin. Subclones K562/MMB, MMG
      and MMF were produced from the parental (K562/P) cell line via limiting dilution
      and their MDR nature confirmed with flow cytometry using an MRK 16 monoclonal
      antibody directed at a surface epitope of the P-gp pump. The pattern of
      increasing P-gp expression in the series K562/P, MMF, MMG and MMB was paralleled
      by increasing resistance to vinblastine and daunorubicin. When the subclones were
      pre-incubated with the chemosensitizing drugs clofazimine and B669, a pattern of
      increasing reversal of resistance to vinblastine and daunorubicin was seen in the
      series K562/P, MMF, MMG and MMB.

PMID- 8564933
TI  - Suppression of the tumorigenicity of human hepatoma hep3B cells by long-term
      retinoic acid treatment.
AB  - We cultured human hepatoma Hep3B cells in the presence of RA (10(-5) M) for 30
      days; the expression of both alpha-fetoprotein and hepatitis B virus surface
      antigen were suppressed over 70% at the transcriptional level by RA treatment.
      The doubling time of RA treated Hep3B cells was slightly different from the
      control cells when they were cultured in 5% fetal calf serum/DMEM medium.
      However, cultured under serum-free conditions, the control Hep3B cells still
      grow, but the RA treated cells could not attach to the substratum of the culture
      plate and stopped growing. In vivo assay indicated that RA treatment completely
      suppressed the tumorigenicity of Hep3B cells in nude mice.

PMID- 8564934
TI  - Nuclear localization of procathepsin L/MEP in ras-transformed mouse fibroblasts.
AB  - It has been well-documented that secretion of procathepsin L is enhanced in ras
      oncogene-transformed cells. In the present study, intracellular localization of
      cathepsin L was investigated by cell fractionation using Nonidet P-40 followed by
      immunoblot analysis. The results showed that a significant amount of procathepsin
      L was detectable in the nuclear fraction of Ha-ras, Ki-ras- and erbB2-transformed
      NIH3T3 mouse fibroblasts while procathepsin L was detected only in the
      cytoplasmic fraction of NIH3T3 cells and v-mos-transformed cells. These results
      suggest that the processing and translocation of cathepsin L are seriously
      impeded in ras- and erbB2-transformed cells.

PMID- 8564935
TI  - 8-Oxo-2'-deoxyguanosine level in lymphocytes DNA of cancer patients undergoing
      radiotherapy.
AB  - We analyzed the level of 8-oxo-2'-deoxyguanosine in lymphocytes DNA of cancer
      patients undergoing radiotherapy. The results of this work indicate that exposure
      of cancer patients to therapeutic doses of ionizing radiation causes significant
      increase of the amount of 8-oxo-dG in DNA isolated from their lymphocytes.

PMID- 8564936
TI  - Synergism of the polyamine analogue, N1,N11-bisethylnorspermine with cis
      diaminedichloroplatinum (II) against murine neoplastic cell lines in vitro and in
      vivo.
AB  - The activities of naturally occurring polyamines are exploited to enhance the
      antitumor activity of cisplatin. The polyamine analogue, N1,N11-bis
      ethylnorspermine (BE-3-3-3) is used at subtherapeutic levels in L1210 leukemia
      suspension cultures and plating efficiency assays of B16 F1 melanoma cells to
      increase the cytotoxic effect of cisplatin seven- and ten-fold, respectively.
      Similar experiments in mice reveal additive effects for DBA/2J mice bearing L1210
      and synergistic effects in C57/B6 mice bearing B16 F1 tumor after optimizing
      combination ratios. In the latter model, at a BE-3-3-3/cisplatin molar ratio of
      250:1, an increased lifespan (ILS) of 56% is recorded during a 9-day dosing
      schedule, whereas BE-3-3-3 at the same dose caused a 21% ILS, and cisplatin only
      exhibited a 7% ILS. Possible reasons for differences between in vitro and in vivo
      activity are discussed.

PMID- 8564937
TI  - The "VANAC team": establishing a cancer prevention team. VA Nurses Against
      Cancer.
AB  - Nurses recognize the increasing need to focus on primary and secondary prevention
      of cancer, yet the demands of current staffing prohibit many nurses from
      organizing and/or participating in cancer prevention and detection activities.
      This article describes an innovative program established at the Bronx Veterans
      Affairs Medical Center (VA). Funded by an American Cancer Society professional
      education grant, nurses at the Bronx VA formed the "VANAC" Team (VA Nurses
      Against Cancer). The camaraderie of a team approach invited generalist nurses to
      become involved with the program. The formation and activities of the team are
      described. After an intensive orientation, nurses participated in a wide range of
      educational activities, including patient education, staff seminars, and
      community presentations. The logistics of arranging such a program are discussed
      and recommendations for future direction are offered. It is hoped that nurses in
      other institutions can adapt the VANAC approach to their individual settings,
      thereby increasing the number of nurses involved in cancer prevention.

PMID- 8564938
TI  - A psychoeducational nursing intervention to enhance coping and affective state in
      newly diagnosed malignant melanoma patients.
AB  - The primary purpose of this study was to determine if a psychoeducational nursing
      intervention including (a) health education, (b) stress management, and (c) the
      teaching of coping skills could enhance the coping behavior and affective state
      of newly diagnosed Stage I/II malignant melanoma patients. The secondary purpose
      was to determine if this intervention could be implemented by a nurse and
      integrated into the overall patient care program. Sixty-one patients were
      randomized to a control condition or an experimental condition that received and
      educational manual plus 3 h of individual nurse teaching. Despite randomization,
      experimental patients had significantly higher baseline distress. By 3 months
      there was a complete reversal of the baseline trend in Profile of Mood States
      (POMS) total mood disturbance (TMD), suggesting that the experimental subjects
      were experiencing less distress over time. Between-group analysis of change
      scores found significant decreases in experimental subjects for POMS TMD,
      fatigue, and Brief Symptom Index (BSI) somatization. Within-group analysis found
      significant experimental decreases for BSI somatization, anxiety, grand total,
      General Severity Index, and Positive Symptom Distress Index as well as for POMS
      anxiety, fatigue, confusion, vigor, and TMD. No significant changes were found
      for controls. Experimental patients were using significantly fewer ineffective
      passive resignation coping strategies than controls at 3 months.

PMID- 8564939
TI  - Menstrual cycles in nurses handling antineoplastic drugs.
AB  - Given the association between high-dose antineoplastic drug therapy and effects
      on gonadal function, a cross-sectional study was designed to explore the
      relationship between low-dose occupational exposure to antineoplastic
      questionnaire survey of the members of two national organizations for nurses was
      conducted, resulting in a sample of 1,458 female subjects. Subjects obtained from
      the two organizations were compared on major demographic and work characteristics
      and were found to be similar on most factors other than occupational exposure to
      antineoplastic drugs. An association was found between menstrual dysfunction and
      current handling of cancer drugs in subjects between ages 30 and 45 years
      [prevalence odds ratio (OR) = 1.6, confidence interval (CI) = 1.3-1.9]. A
      logistic regression analysis demonstrated that subjects ages 30-45 who were
      currently administering antineoplastic drugs had the highest adjusted OR (3.4, CI
      = 1.6-7.3) when compared with subjects with no previous or current handling.
      Additional risk factors significantly associated with menstrual irregularity were
      stress level of work and the interaction of smoking and stress.

PMID- 8564940
TI  - A cancer nursing curriculum guide for baccalaureate nursing education.
AB  - Cancer is a leading cause of morbidity and mortality in the United States,
      affecting one of four Americans. Many nurses without specialized oncology
      preparation will provide counsel and care for people at risk for or with cancer.
      In recognition of the cancer-related educational needs for all nurses in the wide
      variety of health care settings, the American Cancer Society Professors of
      Oncology Nursing provide a curriculum guide for core cancer nursing content in
      undergraduate education for baccalaureate students. It is intended to assist
      educators to define expectations for clinical competencies in cancer care for
      preparing graduates at the baccalaureate level. A variety of educational
      strategies and resources for the educator are suggested to facilitate integration
      of cancer content within existing programs.

PMID- 8564941
TI  - A functional status scale for measuring quality of life outcomes in head and neck
      cancer patients.
AB  - Increased survival rates and disease control dictate that quality of life after
      treatment for head and neck cancer be evaluated. A disease-specific measure was
      developed from interviews with 115 patients, and items reflect the terminology
      used by the patients to describe treatment-related problems and concerns.
      Validity and reliability of this self-report scale were tested with 172 head and
      neck cancer patients and 30 patients who had breast and gynecological cancers.
      Discriminate validity was excellent. Convergent validity of the scale was
      demonstrated by Pearson correlations of 0.68 with a general health status
      measure, 0.68 with the Karnofsky Performance Scale, and 0.76 with the Performance
      Status Scale for Head and Neck Cancer Patients. Reliability as measured by
      Cronbach's alpha was 0.88. Analysis of variance demonstrated that the scale was
      sensitive to differences in stage of disease (p = 0.017) and extent of first
      surgery (p = 0.001) in this cohort of head and neck cancer patients. Psychometric
      evaluation indicates that the scale could be used as an outcome measure between
      groups at one point in time, but future research is needed to establish the
      scale's sensitivity to positive and negative changes in functional status for
      longitudinal studies.

PMID- 8564942
TI  - The Bethesda system for classification of Pap smears: the clinical experience of
      one cancer screening center.
AB  - Since the initiation of the Bethesda System for the classification of
      cervical/vaginal cytology in 1988, anecdotal reports suggest that there may be an
      increased number of referrals for abnormalities. The purpose of this
      retrospective chart review (n = 533) was to describe (a) the adequacy of samples
      collected by an advanced practice nurse; (b) a comparison of the findings and
      referrals from Pap smears collected using the old numerical (I-V) system and the
      Bethesda system; and (c) findings from the follow-up of referrals of nonspecific
      Pap smears. A total of 108 smears were interpreted using the numerical system and
      425 in the Bethesda System. Results included that 90% of the specimens were
      considered adequate for interpretation. Recommendations for repeat smears in
      women with nonspecific results were made to 128 women; 68 (53%) had a repeat Pap
      smear done. Of these women, 39 (57%) had a normal smear on repeat and 29 (43%)
      had a persistent nonspecific smear. When the numerical system was used, < 10%
      were referred for a repeat smear or further evaluation. In this study, there
      appears to be an increase in the number of referrals for further evaluation with
      the use of the Bethesda system. Nurses need to consider various ways to educate
      women regarding the changes due to the Bethesda system and the clinical
      implications of the new system.

PMID- 8564943
TI  - The psychosocial morbidity of breast cancer patients with lymphoedema.
AB  - Lymphoedema is a problem for many women after treatment for breast cancer,
      leading to physical, psychosocial, and psychological problems, which have been
      acknowledged but are poorly understood. This article discusses the findings of
      two studies that used the Psychosocial Adjustment to Illness Scale to examine the
      psychosocial morbidity of patients with breast cancer with lymphoedema. Women
      with lymphoedema were found to experience increased psychosocial maladjustment
      and psychological morbidity to their disease and lymphoedema when compared with a
      group of patients with breast cancer who did not have lymphoedema. These
      difficulties were not related to the degree of swelling present and persisted
      after 6 months of specialised treatment to the swollen arm. The findings indicate
      that the development of lymphoedema in patients with breast cancer carries
      psychosocial and psychological implications that should be acknowledged and
      addressed at an early stage by a trained health-care professional.

PMID- 8564944
TI  - Functions of a breast cancer support group as perceived by the participants: an
      ethnographic study.
AB  - The purpose of this study was to obtain an understanding of the functions of a
      breast cancer support group as perceived by the participants. An ethnographic
      method of research was used. Data were collected by participant observation and
      tape-recorded interviews during the weekly support group meetings. The
      convenience sample included one professional group leader and 15 women diagnosed
      with breast cancer within a range of 2 weeks to 7 years. Two key informants were
      chosen to clarify and validate data. Content analysis was performed on the data
      obtained from the tape recordings of 10 group meetings and from the two key
      informant interviews. Three categories of functions of the breast cancer support
      group emerged from the data analysis, including exchanging information, sharing
      the illness experience, and providing strength. As the incidence rate of breast
      cancer continues to increase, it is imperative that nurses recognize the physical
      and psychological reactions to breast cancer and identify sources of social
      support for women. Nurses should be cognizant of the functions of a breast cancer
      support group in order to share this information with women and encourage them to
      actively participate with others sharing the same experience.

PMID- 8564945
TI  - Biotherapy module III. Interferons.

PMID- 8564946
TI  - Presence of potent transcriptional activation domains in the predisposing
      tuberous sclerosis (Tsc2) gene product of the Eker rat model.
AB  - The Eker rat hereditary renal carcinoma is an excellent example of Mendelian
      dominant predisposition to a specific cancer in an experimental animal. We
      recently reported that a germline insertion in the rat homologue of the human
      tuberous sclerosis gene (TSC2) gives rise to dominantly inherited cancer in the
      Eker rat model, as well as a tumor suppressor nature for the Tsc2 gene function.
      We also showed a strong conservation between the rat and human gene products. The
      molecular function of the Tsc2 gene product (called "tuberin" in the human case)
      is not yet understood, although it contains a short amino acid sequence
      homologous to ras family GTPase-activating proteins (Rap1GAP). Here, we describe
      transcriptional activation domains (AD1 and AD2) in the carboxyl terminus of the
      Tsc2 product (in exons 30 and 32 and exon 41, respectively). The Eker insertional
      mutation (intron 30) disrupts their transcriptional activity. Whereas a COOH
      terminal truncated Tsc2 protein was localized in the nucleus, the full-length
      protein is found predominantly in the perinuclear region of cytoplasm. The
      present demonstration of transcriptional activation domains in the Tsc2 gene
      provides clues for studying its role in renal carcinogenesis.

PMID- 8564947
TI  - Histone H3 messenger RNA in situ hybridization correlates with in vivo
      bromodeoxyuridine labeling of S-phase cells in rat colonic epithelium.
AB  - Measurements of cell cycle phase fractions, particularly S-phase, are useful for
      studies of cell biology and carcinogenesis. Up-regulation of histone gene
      expression is tightly coupled to the G1-S-phase transition of the cell cycle, and
      mRNA levels rise 30-100-fold during S-phase. Labeling of histone H3 mRNA using in
      situ hybridization (ISH) was assessed as a measure of S-phase cells and compared
      with that found using in vivo 5-bromodeoxyuridine (BrdUrd) labeling in formalin
      fixed rat colonic crypts under baseline, modified 72-h starvation, and 24-h
      refeeding conditions. The labeling index scored in single-labeled sections by
      histone H3 ISH tightly correlated with that found by in vivo BrdUrd labeling (r =
      0.99, p < 0.0001) and clearly discriminated between the control, starved, and
      refed states (P < 0.001). In 180 crypt sections double labeled using histone H3
      ISH and BrdUrd, 92% of 1572 labeled cells exhibited both nuclear BrdUrd and
      cytoplasmic histone H3 label. It is concluded that histone H3 ISH is an accurate
      measure of the S-phase fraction and provides an alternative to in vivo BrdUrd
      labeling in rat colon. This finding warrants validation in human studies.

PMID- 8564948
TI  - Cleavage of retinoblastoma protein during apoptosis: an interleukin 1 beta
      converting enzyme-like protease as candidate.
AB  - We had found that in an early stage of DNA damage-induced, p53-independent
      apoptosis, retinoblastoma (RB) protein is hypophosphorylated to a p115 form by an
      activated serine/threonine phosphatase. Here, we report that accompanying the
      internucleosomal fragmentation of DNA, the newly formed p115/hypo/RB was
      immediately cleaved into at least two fragments, p68 and p48. The RB cleavage
      activity possessed properties of interleukin 1 beta-converting enzyme family.
      Addition of a specific tetrapeptide interleukin 1 beta-converting enzyme
      inhibitor prevented cleavage of p115/hypo/RB and early apoptotic cells from
      undergoing further apoptosis. We suggest that activation of the RB phosphatase
      and protease may be involved in mediating the two physiological stages of
      apoptosis, commitment and execution, respectively.

PMID- 8564949
TI  - Elevation of interferon beta-inducible proteins in ataxia telangiectasia cells.
AB  - The recently cloned ATM gene has been shown to bear considerable homology to
      phosphatidylinositol 3 kinases and, therefore, its product may function in signal
      transduction. In this study, we report constitutively elevated levels of two IFN
      beta-inducible proteins, ubiquitin cross-reactive protein (UCRP), and low
      molecular weight protein (LMP2), in human fibroblasts with the inherited disease
      ataxia telangiectasia (AT). Using immunoblotting, it was found that a M(r) 15,000
      band representing free UCRP was hardly detectable in normal cells, while it was
      the predominant band in AT cells. Similarly, the expression of a M(r) 23,000
      protein, LMP2 was found to be higher in AT cells than in normal cells. Culturing
      three successive passages of the AT cell line in the presence of different
      concentrations of neutralizing antibodies against IFN-beta caused partial and
      complete reduction, respectively, of the free UCRP and LMP2 signals to normal
      levels. These results indicate that UCRP and LMP2 pools may be basally elevated
      in AT cells due to constitutive activation of the IFN-beta induction pathway and
      are in keeping with the recently reported constitutive activation of the NF
      kappaB transcriptional activator in AT cells.

PMID- 8564950
TI  - A new member of the proprotein convertase gene family (LPC) is located at a
      chromosome translocation breakpoint in lymphomas.
AB  - A new member of the proprotein convertase gene family (LPC) has been identified
      at a chromosome translocation breakpoint occurring in a high grade lymphoma. The
      translocation t(11;14)(q23;q32) has been molecularly cloned and shown to be the
      result of a fusion between an intron in the 3' -untranslated region of LPC with a
      sequence close to the switch region S gamma 4 of the IGH locus. The LPC gene
      encodes a protein of 785 amino acids with substantial homology to furin and the
      other members of the proprotein convertase family and represents a novel target
      for chromosome translocation and subsequent deregulation.

PMID- 8564951
TI  - Detection of 1, N2-propanodeoxyguanosine adducts as potential endogenous DNA
      lesions in rodent and human tissues.
AB  - Our previous study (R.G. Nath and F-L. Chung; Proc. Natl. Acad. Sci. USA, 91:
      7491-7495, 1994), using a 32P postlabeling method combined with high-performance
      liquid chromatography specifically developed for exocyclic adducts, has shown
      that acrolein- and crotonaldehyde-derived 1,N2-propanodeoxyguanosine adducts (AdG
      and CdG, respectively) are present in the liver DNA from humans and rodents
      without carcinogen treatment. Those findings raised important questions regarding
      their role as potential endogenous DNA lesions in carcinogenesis. In this study,
      using a similar assay, we examined a variety of tissues from untreated rats and
      mice (lung, kidney, brain, breast, prostate, colon, skin, and leukocytes) and
      detected AdG and CdG in the DNA of these tissues. More significantly, we also
      obtained evidence for the presence of these adducts in the DNA of human
      leukocytes and mammary glands. The identities of these adducts were verified by
      comigration of 3', 5' -bisphosphates of the 32P-labeled adduct from DNA with the
      synthetic standards in a reversed-phased high-performance liquid chromatography.
      Additional proof of identities was provided by enzymatic conversion of AdG and
      CdG 3',5' -bisphosphates to the corresponding 5'-monophosphates, followed by
      comigration with their synthetic standards. The estimated ranges of total AdG and
      CdG modifications in DNA of various tissues were from 0.10 to 1.60 mumol/mol
      guanine for humans, based on the recoveries of external standards. This study
      demonstrated the ubiquity of these adducts in various tissues, suggesting their
      potential role as endogeneous DNA lesions in rodents and humans.

PMID- 8564952
TI  - A matrix attachment region (MAR)-binding activity due to a p114 kilodalton
      protein is found only in human breast carcinomas and not in normal and benign
      breast disease tissues.
AB  - A M(r) 114,000 protein (p114) that specifically binds to nuclear matrix
      attachment DNA (matrix attachment region, MAR) from a breast carcinoma cell line
      SK-BR-3 was purified to near homogeneity. p114 strongly binds to a wild-type A+T
      rich MAR probe with high unwinding propensity with a dissociation constant (Kd)
      of 10(-9), while it exhibits substantially reduced binding to a mutated A+T-rich
      non-MAR probe, which lacks unwinding propensity. This binding specificity and
      affinity is similar to the previously cloned thymocyte-associated MAR-binding
      protein SATB1. By Southwestern blot analysis, the MAR-binding activity of p114 is
      detectable in human breast carcinomas but is undetectable in normal breast
      tissues, benign breast diseases, and immortalized epithelial MCF-10A cells. Thus,
      the MAR-binding activity of p114 is not merely reflecting cell proliferation, but
      it strongly associates with breast carcinomas. The p114 MAR-binding activity was
      found in all 43 human breast carcinoma specimens tested, without exception. Much
      stronger p114 MAR-binding activity was detected in poorly differentiated than
      well-differentiated carcinomas. p114 may be a reliable diagnostic and possibly
      prognostic marker for breast cancer.

PMID- 8564953
TI  - Accelerated growth of melanomas after specific immune destruction of tumor stroma
      in a mouse model.
AB  - Destruction of the entire stroma in a tumor could provide a stringent test of the
      prospects for tumor eradication in a single treatment. This possibility was
      investigated by experimental immune destruction of the stroma in a mouse melanoma
      model. Melanomas were first produced by grafting skin from transgenic C57BL/6
      females of high-melanoma susceptibility to low-susceptibility transgenic males so
      that the malignant cells would be genetically female and the stromal cells
      genetically male. Subcutaneous transplant lines were then established from the
      melanotic and the amelanotic zones of such a melanoma and were carried in
      transgenic male hosts to ensure the male composition of the stroma. Thus, the
      male-specific H-Y histocompatibility antigen, which is ubiquitously expressed on
      male cells, could provide the target for an immune attack against the stroma. The
      transplant lines were next passaged once in transgenic females preimmunized
      against the H-Y antigen by having received and rejected a graft of C57BL/6
      nontransgenic male skin. The antistromal immune response of these hosts did not
      prevent recovery of the tumors, which required a substantially prolonged latency.
      However, after retransplantation to nonimmunized males and females, the latency
      was markedly shortened from the original level. Thus, the treatment had
      indirectly selected for more rapidly growing tumor cells and hastened malignant
      progression.

PMID- 8564954
TI  - Interleukin 12 potentiates the curative effect of a vaccine based on interleukin
      2-transduced tumor cells.
AB  - The purpose of these studies was to determine whether systemic administration of
      recombinant interleukin 12 (rIL-12) is able to potentiate an initial, but
      insufficient T-cell antitumor response. Mice challenged with carcinoma cells
      engineered to release interleukin 2 (IL-2) and displaying such a response
      received single or multiple i.p. injections of rIL-12. This combination of
      systemic rIL-12 and local IL-2 increased the percentage of mice that rejected two
      different IL-2 gene-transduced tumors. In another set of experiments more closely
      resembling a clinical situation, IL-2 gene-transduced tumors were used as
      vaccines in an attempt to cure mice bearing wild-type parental tumors. The
      combination of these vaccines with systemic rIL-12 cured mice more effectively
      than rIL-12 and IL-2 gene-transduced tumor vaccines alone.

PMID- 8564955
TI  - Germ line mutation at BRCA1 affects the histoprognostic grade in hereditary
      breast cancer.
AB  - Histoprognostic grade is a determinant parameter to select the initial
      therapeutic strategy in breast cancer. Our aim was to analyze the grade
      repartition in BRCA1-associated breast cancer (BC) and to explore the possible
      connections between grade and the BRCA1 gene function. We first compared 27 BRCA1
      associated BCs from 14 families with 4,461 cases from an administrative district
      registry and 242 cases from a hospital-based registry, matching for grade and
      constitutive elements, and then considered their repartition in families. We
      observed a prevalence of grade 3 (P < 0.0001) in BRCA1-associated BC. This was
      attributed mainly to nuclear polymorphism (P < 0.0001), mitotic activity (P <
      0.0001), and tubular differentiation (P = 0.0004), implying that BRCA1-associated
      BCs are highly proliferating tumors. Moreover, it is suggested that grade
      segregates as a genetic trait within families (P = 0.0015), and this was
      attributed to the mitotic index segregation only (P = 0.0005). Therefore grade,
      through its components, could be interpreted as the morphological translation of
      the BRCA1 germ line mutation. Thus, a genotype-phenotype correlation may exist
      between the type of mutation and the aggressiveness of the disease. These
      findings are bound to have an important impact in the care management of
      hereditary breast cancer at the individual and at the familial level and in the
      comprehensive approach of breast cancer development.

PMID- 8564956
TI  - Role of p21 in prostaglandin A2-mediated cellular arrest and death.
AB  - Prostaglandin A2 (PGA2) treatment induces growth arrest of most cells, and we
      have recently shown that, for breast carcinoma MCF-7 cells, this is correlated
      with an induction of the cyclin-dependent kinase inhibitor p21 and reduced cyclin
      dependent kinase 2 activity. In this study, we demonstrate that, in RKO cells,
      PGA2 treatment fails to induce growth arrest, but rather results in significant
      cell death. These effects are correlated with lack of p21 induction and enhanced
      cyclin-dependent kinase 2 activity. Reduction of endogenous p21 expression in MCF
      7 cells through expression of antisense p21 resulted in a response pattern
      approaching that seen in RKO cells, characterized by diminished growth arrest and
      increased death. These findings support a role for p21 in PGA2-mediated growth
      arrest, which we propose serves to prevent cell death caused by inappropriate
      cell cycle progression.

PMID- 8564957
TI  - Loss of H19 imprinting in esophageal cancer.
AB  - Recent articles have reported that loss of imprinting (LOI) of the endogenous
      gene H19 was frequently found in lung cancer and chorio-carcinoma, common
      adulthood cancers. Consequently, we examined the status of genomic imprinting of
      H19 in 29 esophageal and 48 colorectal cancer specimens, and studied its relation
      to the expression of H19. Of 12 esophageal cancer specimens heterozygous for the
      RsaI polymorphism, 6 (50%) exhibited LOI of H19, but none of the 18 colorectal
      cancer specimens heterozygous for the RsaI polymorphism exhibited LOI of H19. The
      present study suggests that LOI of H19 may play an important role in the
      pathogenesis of esophageal cancer. Moreover, H19 expression was frequently
      abundant in both cancers, and all six esophageal cancers carried LOI with
      overexpressed H19. Therefore, this overexpression of H19 seems to be an important
      phenomenon for the development of esophageal and colorectal cancer cells.

PMID- 8564958
TI  - Inhibition of tumor promoter-induced transformation by retinoids that
      transrepress AP-1 without transactivating retinoic acid response element.
AB  - Both retinoic acid (RA) treatment and dominant-negative c-Jun mutant expression
      effectively inhibit phorbol ester-induced AP-1 activity and induced neoplastic
      transformation in mouse epidermal JB6 cells. However, both reagents also target
      non-AP-1 molecules in addition. Because liganded retinoic acid receptors interact
      with and transactivate RA response elements (RAREs) on DNA, as well as interact
      with Jun protein to block AP-1 activity, the question arises as to which of these
      two activities of retinoids is responsible for antitumor-promoting activity. To
      address this question we generated JB6 promotion-sensitive (P+) cell lines that
      are stably transfected with a construct containing the collagenase promoter
      bearing one AP-1-binding site that drives a luciferase reporter gene. The stable
      collagenase-luciferase-transfected cell lines showed 1.5-3.5-fold enhanced AP-1
      activity when treated with 12-0-tetradecanoyl-phorbol-13-acetate (TPA). Up to 90%
      of TPA-induced AP-1 activity was blocked by retinoids SR11238, SR11302, or trans
      RA, but not by retinoid SR11235. Of these retinoids, only RA and SR11235 were
      able to transactivate RARE-dependent gene expression. Transrepression of TPA
      induced AP-1 and transactivation of RARE by RA, SR11238, and SR11302 were
      concentration dependent at 10(-10) to 10(-6) M retinoid. When tested for activity
      in inhibiting tumor promoter-induced transformation in JB6 P+ cells, the
      retinoids specific for AP-1 transrepression were inhibitory, whereas SR11235,
      which only activated RARE, showed little effect. We thus conclude that the AP-1
      blocking activity of retinoids is likely to be responsible for the antitumor
      promoting activity. This result, together with the observation that dominant
      negative Jun blocks transformation, argues for a requirement of induced AP-1 in
      the tumor promoter-induced transformation process.

PMID- 8564959
TI  - Homozygous deletion map at 18q21.1 in pancreatic cancer.
AB  - Absolute genetic differences between neoplastic and nonneoplastic cells can be
      discerned at sites of homozygous deletions. These deletions are of critical
      interest because they might be useful in the identification of defective
      biochemical pathways in neoplastic cells, and subsequently for the development of
      new treatment strategies in human cancer. We identified an area at 18q21.1
      involved by homozygous deletions in 30% of pancreatic carcinomas. To characterize
      the homozygous deletions, we constructed a detailed physical map of nearly 2 Mb,
      containing yeast artificial chromosomes, P1-derived artificial chromosomes,
      cosmids and 24 sequence-tagged sites. The homozygously deleted are contained a
      new candidate tumor-suppressor gene (DPC4). To date, 23 (64%) of 35 pancreatic
      carcinomas carry at least one homozygous deletion at a published locus. The study
      of the total gene content of these loci, facilitated by the sequence-tagged site
      markers and maps of these regions, should help to reveal the absolute biochemical
      differences between neoplastic and nonneoplastic cells for a common human tumor.

PMID- 8564960
TI  - Effects of endogenously activated transforming growth factor-beta on growth and
      differentiation of retinoic acid-treated HL-60 cells.
AB  - Retinoic acid (RA)-treated HL-60 cells were used as a model to study
      differentiation of granulocytic leukemias. RA induces these cells to mature into
      granulocytes and to decrease growth. Mediators of these RA effects have not been
      identified definitively, but transforming growth factor-beta (TGF-beta) has been
      implicated in regulating proliferation and differentiation of myelogenous
      leukemic cells. The role of TGF-beta in RA-dependent differentiation and
      cessation of growth was examined by adding neutralizing anti-TGF-beta IgG to RA
      treated HL-60 cells, followed by assessing cell growth and markers of
      granulocytic differentiation over 5 days. After addition of neutralizing anti-TGF
      beta IgG, growth of RA-treated HL-60 cells was maintained at control levels, but
      granulocytic differentiation continued. These experiments demonstrated that the
      antiproliferative activity of RA was TGF-beta dependent but that differentiation
      was not. Because most cell types secrete TGF-beta in a biologically inactive
      complex, a TGF-beta-dependent effect requires cells to activate the latent form
      of TGF-beta. Active and total TGF-beta levels were quantitated in media harvested
      from control and RA-treated cells using a luciferase-based bioassay for TGF-beta
      activity. Similar levels of total TGF-beta were observed between control and RA
      treated cells. RA-treated cells produced active TGF-beta (18-24 pg/ml) after 1,
      2, and 3 days of treatment, whereas negligible levels were produced by control
      cultures. Activation of endogenous latent TGF-beta by RA-treated cells occurred
      through a plasmin-independent mechanism.

PMID- 8564961
TI  - Cell cycle synchrony unmasks the influence of p53 function on radiosensitivity of
      human glioblastoma cells.
AB  - Although ionizing radiation causes DNA damage that can play a role in
      tumorigenesis, such irradiation is also an important modality of cancer therapy.
      We studied the radiation response of the U-87 MG human glioblastoma cell line and
      transfected derivatives in which p53 function had been inactivated. Although
      little effect of p53 on the radiation sensitivity of asynchronously growing
      cultures could be detected, inactivation of p53 resulted in a large increase in
      clonogenic survival when cells synchronized by mitotic selection were irradiated
      in early G1. The radiation dose sufficient to reduce cellular clonogenicity by 1
      log in cells expressing functional p53 was 3.26 +/- 0.12 Gy, whereas a much
      higher dose (7.41 +/- 0.44 Gy) was required to achieve the same killing effect in
      cells in which p53 was inactivated. Apoptosis was excluded as a probable
      mechanism contributing to the radiosensitivity of these cells. Fluorescence
      activated cell sorter analysis, continuous labeling with tritiated thymidine, and
      time-lapse videomicroscopy documented the first example of a prolonged p53
      dependent G1 arrest induced by ionizing radiation during the first
      postirradiation cell cycle of tumor cells, suggesting a role for G1 arrest in
      determining the sensitivity of these cells to irradiation.

PMID- 8564962
TI  - Mechanisms of interleukin-2-induced hepatic toxicity.
AB  - Interleukin 2 (IL-2) mediates the regression of metastatic cancer, but its
      clinical use is limited by associated toxicities including hepatic dysfunction.
      To determine the mechanism for IL-2-induced hepatic dysfunction, we hypothesized
      that IL-2 activation of Kupffer cells causes leukocyte-endothelial adhesion and
      decreases hepatic sinusoidal blood flow. C57BL/6 mice were given injections of
      latex particles and prepared for intravital hepatic microscopy 2 h after i.p. IL
      2 administration. Liver tissue was also prepared to quantitate hepatic tumor
      necrosis factor (TNF) mRNA and processed for light and electron microscopy.
      Phagocytosing Kupffer cells and leukocytes adherent to the endothelium were
      counted, and surface sinusoidal blood flow was quantitated. Kupffer cell activity
      was quantitated as the ratio of phagocytosing Kupffer cells to sinusoidal blood
      flow. IL-2 significantly increased Kupffer cell activity (0.56 +/- 0.05 for
      controls versus 0.84 +/- 0.05 for IL-2), significantly caused leukocyte
      endothelial adhesion (26.7 +/- 7.9 for controls versus 87.0 +/- 27.6 for IL-2,
      WBC/mm2 endothelial surface), and significantly decreased the number of sinusoids
      containing blood flow per microscopic field (6.66 +/- 0.15 for controls versus
      5.79 +/- 0.13 for IL-2) without causing changes in systemic hemodynamic
      parameters. In IL-2 treated livers, light and electron microscopy showed the
      constriction of sinusoids associated with swollen or ruptured mitochondria, which
      was consistent with hypoxic deterioration near central venules. Adherent
      platelets, neutrophils, and lymphocytes within sinusoids and central venules were
      also observed. PCR revealed that IL-2 significantly induced TNF mRNA expression
      in the liver. These data suggest that IL-2 activates Kupffer cells in association
      with the release of monokines including TNF, which causes activation of
      circulating leukocytes as well as hepatic sinusoidal endothelial cells. The
      resultant leukocyte and platelet adhesion to the endothelium may then physically
      impede the sinusoidal microcirculation, resulting in microscopic areas of hepatic
      ischemia and explaining the mechanism of IL-2-induced hepatic dysfunction.

PMID- 8564963
TI  - Impairment of sodium pump and Na+/H+ antiport in erythrocytes isolated from
      cancer patients.
AB  - We sought to determine whether the impairment of sodium pump activity and Na+/H+
      exchange reported in tumorigenic cells was specific to these cells or more
      general. Sodium pump activity and Na+/H+ exchange were measured in erythrocytes
      from 49 cancer patients and 51 healthy subjects. Cancer patients with a newly
      detected cancer or in relapse and without associated pathologies known to modify
      these sodium transporters were included in this study. Two sodium pump statuses
      reflecting its physiological modulation were evidenced for healthy subjects (10.3
      +/- 0.2 and 19.4 +/- 0.8 mW/liter of cells). In cancer patients, only one basal
      status lower than those of controls was observed (8.3 +/- 0.5 mW/liter of cells;
      P < 0.001). Cooperativity of the Na+/H+ antiporter is the same in cancer patients
      and controls (2.58 +/- 0.27 versus 2.60 +/- 0.15). The intracellular pH (pHi)
      dependence curve of the antiporter was shifted toward more acidic values, and
      optimal pH1 was lower in cancer patients than in controls (5.80 +/- 0.03 versus
      6.08 +/- 0.02; P < 0.0001). The mean maximal rate and the Km of H+ for the Na+/H+
      antiporter were higher: 8.4 +/- 1.2 versus 4.6 +/- 0.4 mmol H+/liter of cells/h
      (P < 0.01) and 514 +/- 12 versus 322 +/- 16 nM (P < 0.05), respectively.
      Alterations of these Na+ transporters, therefore, were not restricted to
      cancerous cells. Among the alterations, the acidic shift in the pHi dependence of
      Na+/H+ exchange appears associated with cancer because this behavior has never
      been reported in other pathologies.

PMID- 8564964
TI  - Temporary ex vivo inhibition of the expression of the human oncogene HER2 (NEU)
      by a triple helix-forming oligonucleotide.
AB  - A 28-base phosphodiester triple helix-forming oligonucleotide, mostly G and A
      containing, targeted to a polypurine tract interrupted by a purine-pyrimidine
      inversion, situated upstream from the TATA box of the promoter of the human HER2
      gene, was conceived by computer modeling. The "energetically best choice" was
      oligo 28(C), which formed the triple helix in vitro, as proved by gel retardation
      and Fourier transform infrared spectroscopy. When administered as a complex with
      lipofectin, fluorescence confocal microscopy and electrophoresis confirmed the
      delivery and persistence of this unprotected oligonucleotide inside MCF7 (breast
      cancer) cells. At a concentration of 2 microM, the oligonucleotide reduced within
      6 h the HER2 mRNA level to 42% (Northern blot) but did not interfere with the
      transcription of a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase.
      During the first day of administration at 0.22 microM, it lowered to 59% the HER2
      protein in treated, as compared to nontreated, cells (ELISA). The effect was
      sequence specific when compared to that of five different negative controls, and
      it was target selective when compared to the expression of a related, nontargeted
      protein, the epidermal growth factor receptor. By day 2, the inhibitory effect
      was overcome by replenishment reactions.

PMID- 8564965
TI  - Increased epithelial cell proliferation in the colon of patients with acromegaly.
AB  - To gain insight into the possible physiological mechanisms responsible for the
      increased incidence of colonic neoplasms in patients with acromegaly, a
      prospective cohort study was carried out in 30 patients with acromegaly, a
      prospective cohort study was carried out in 30 patients with acromegaly. Seven
      patients had newly diagnosed acromegaly and 23 were studied during follow-up.
      Serum growth hormone and insulin-like growth factor-1 (IGF-1) were determined on
      two separate occasions. During diagnostic endoscopy, mucosal biopsies were
      obtained for immunohistochemical determination of sigmoidal epithelial cell
      proliferation, expressed as labeling index (LI). Duodenal and fecal bile acid
      analyses were performed using gas-liquid chromatography. Results were compared
      with normal ranges of the laboratory. An increased overall LI was found in 54% of
      the patients. Increased LI of the luminal, middle, and basal crypt compartments
      was found in 11, 64, and 28%, respectively. Similarly, comparisons of the mean +/
      SEM of the overall LI and the LI of the middle and basal compartments between
      acromegalic patients and a control group showed overall LI 10.0 +/- 0.8% versus
      5.7 +/- 0.6% (P < 0.001), middle LI 12.1 +/- 1.2% versus 5.0 +/- 0.6% (P <
      0.001), and basal LI 17.1 +/- 1.3% versus 10.8 +/- 1.3% (P < 0.01). Duodenal and
      fecal bile acid proportions were within the normal ranges of the laboratory.
      There was a positive correlation between growth hormone and overall LI (r = 0.55,
      P < 0.01) by least square regression analysis. There was no correlation between
      duodenal bile acid composition and hormone levels. The proportion of secondary
      bile acids in feces correlated with growth hormone (r = 0.55, P < 0.05) as well
      as with IGF-1 (r = 0.59, P < 0.05). With multiple regression analyses, only a
      relation between overall LI and IGF-1 (P = 0.007) remained to hold true.
      Increased epithelial cell proliferation, most probably due to a direct
      stimulatory effect of especially IGF-1, contributes to the increased risk of
      colonic neoplasms in acromegaly.

PMID- 8564966
TI  - Acetylator genotype (NAT2)-dependent formation of aberrant crypts in congenic
      Syrian hamsters administered 3,2'-dimethyl-4-aminobiphenyl.
AB  - Some but not all human epidemiological studies suggest a higher incidence of
      colon cancer in rapid acetylator individuals. Aberrant crypts, the earliest
      morphologically evident preneoplastic lesions in chemical colon carcinogenesis,
      were measured in rapid and slow acetylator congenic Syrian hamsters administered
      3,2' -dimethyl-4-aminobiphenyl, an aromatic amine colon carcinogen, to
      investigate the specific role of the acetylator genotype (NAT2) in colon
      carcinogenesis. Age-matched rapid (Bio. 82.73/H-Patr) and slow (Bio. 82.73/ H
      Pat(s) acetylator female Syrian hamsters congenic at the NAT2 locus received a
      s.c. injection of 3,2' -dimethyl-4-aminobiphenyl (100 mg/kg) at the start of
      weeks 1 and 2. After 10 and 14 weeks, the hamsters were sacrificed, and each
      whole cecum, colon, and rectum was stained with 0.2% methylene blue, fixed in 4%
      paraformaldehyde, and examined under a dissecting microscope for the presence of
      aberrant crypts. Aberrant crypts were identified in the cecums and colons of both
      rapid and slow acetylator congenic hamsters treated with 3,2' -dimethyl-4
      aminobiphenyl but not in vehicle controls. The size of the aberrant crypt foci
      was larger in the colon than in the cecum, and the highest frequency of aberrant
      crypt foci was observed in the cecum. No aberrant crypts were detected in the
      rectum. The frequency of aberrant crypt foci was significantly higher (2-3-fold)
      in rapid versus slow acetylator congenic hamsters in both cecum (P = 0.0352) and
      colon (P = 0.0006). These results support human epidemiological studies that
      suggest the rapid acetylator genotype is associated with higher risk of colon
      cancer induced by aromatic amines.

PMID- 8564967
TI  - Modulating effect of amount and types of dietary fat on colonic mucosal
      phospholipase A2, phosphatidylinositol-specific phospholipase C activities, and
      cyclooxygenase metabolite formation during different stages of colon tumor
      promotion in male F344 rats.
AB  - Epidemiological and laboratory animal model studies suggest that the effect of
      dietary fat in colon carcinogenesis depends not only on the amount but on its
      fatty acid composition. Animal model studies demonstrated that high dietary corn
      oil or safflower oil rich in omega-6 fatty acids increased the colon tumor
      promotion, whereas diets containing fish oil high in omega-3 fatty acids had no
      such enhancing effect. One of the mechanisms by which high dietary fat enhances
      colon carcinogenesis may be through the modulation of colonic mucosal
      phospholipase A2 (PLA2) and phosphatidylinositol-specific phospholipase C (PI
      PLC), which are dominant pathways for arachidonic acid release and formation of
      eicosanoids. PI-PLC is also responsible for diacylglycerol formation and protein
      kinase C-dependent signal transduction and cell proliferation. In the present
      study, we investigated the modulating effect of high fat diets rich in omega-3
      and omega-6 fatty acids on colonic mucosal PLA2, PI-PLC activities, and
      eicosanoid (prostaglandins and thromboxane B2) formation from arachidonic acid
      via cyclooxygenase (COX) during different stages of azoxymethane (AOM)-induced
      colon carcinogenesis in male F344 rats. At 5 weeks of age, groups of animals were
      fed the low-fat diet containing 5% corn oil. Beginning at 7 weeks of age, all
      animals except those intended for vehicle treatment received AOM s.c. once weekly
      for 2 weeks at a dose rate of 15 mg/kg body weight. Vehicle-treated groups
      received an equal volume of normal saline. One day after the second AOM or
      vehicle treatment, groups of animals were transferred to experimental diets
      containing 23.5% corn oil and 20.5% fish oil + 3% corn oil, whereas one group
      continued on the low-fat diet containing 5% corn oil. Groups of animals were then
      sacrificed at weeks 1, 12, and 36 after the second AOM-or saline-treatment.
      Colonic mucosa harvested at weeks 1, 12, and 36 and colonic tumors obtained at
      week 36 were analyzed for PLA2, PI-PLC, and eicosanoid formation from arachidonic
      acid by the action of COX. The results demonstrate that colon carcinogen
      treatment increases the activities of colonic mucosal PLA2 and PI-PLC and the
      formation of prostaglandins and thromboxane A2 from arachidonic acid through COX
      throughout the study period compared to saline-treated animals fed similar diets.
      The activities of PLA2, PI-PLC, and COX were significantly higher in colon tumors
      compared to colonic mucosa. These results also demonstrate that a high-fat diet
      containing corn oil increases colonic mucosal and tumor PLA2 and PI-PLC and the
      formation of prostaglandins and thromboxane B2 by the action of COX as compared
      to low dietary corn oil or a diet high in fish oil. The results of our study
      offer one of the mechanisms by which the amount and types of dietary fat modulate
      colon carcinogenesis.

PMID- 8564968
TI  - MKT-077, a novel rhodacyanine dye in clinical trials, exhibits anticarcinoma
      activity in preclinical studies based on selective mitochondrial accumulation.
AB  - MKT-077 (formerly known as FJ-776) is a newly synthesized, highly water-soluble (
      > 200 mg/ml) rhodacyanine dye that exhibits significant antitumor activity in a
      variety of model systems. In culture, MKT-077 inhibits the growth of five human
      cancer cell lines (colon carcinoma CX-1, breast carcinoma MCF-7, pancreatic
      carcinoma (CRL 1420, bladder transitional cell carcinoma EJ, and melanoma LOX)
      but not monkey kidney CV-1, an indicator cell line for normal epithelial cells.
      In nude mice, MKT-077 inhibits the growth of s.c. implanted human renal carcinoma
      A498 and human prostate carcinoma DU145 and prolongs the survival of mice bearing
      i.p. implanted human melanoma LOX (tumor:control = 344%). Subcellular
      localization indicates that MKT-077 is taken up and retained by mitochondria, and
      flow cytometric analysis suggests that CX-1 cells take up MKT-077 to a much
      greater extent than CV-1 cells. Quantitation of MKT-077 uptake by ethanol
      extraction shows that CX-1 cells accumulate 65-fold more MKT-077 than do CV-1
      cells. MKT-077 is the first delocalized lipophilic cation with a favorable
      pharmacological and toxicological profile in preclinical studies. MKT-077 is now
      being investigated in Phase I clinical trials.

PMID- 8564969
TI  - Selective damage to carcinoma mitochondria by the rhodacyanine MKT-077.
AB  - We investigated the mitochondrial toxicity of the lipophilic cation, MKT-077, and
      the role of mitochondria in selective malignant cell killing by this compound by
      examining the effect of MKT-077 on mitochondrial structure and function in
      treated cells and in isolated organelles. Results of this study demonstrate
      changes in mitochondrial ultrastructure that are induced by MKT-077 treatment in
      carcinoma cells but not in similarly treated normal epithelial cells. In
      addition, MKT-077 was found to inhibit respiratory activity in isolated intact
      mitochondria and electron transport activity in freeze-thawed mitochondrial
      membrane fragments in a dose-dependent manner. The concentration of MKT-077
      necessary to obtain half-maximal inhibition of ADP-stimulated respiration was
      approximately 4-fold greater in mitochondria isolated from cells of the normal
      epithelial cell line, CV-1 (15 micrograms MKT-077/mg protein), as compared to the
      human colon carcinoma cell line, CX-1 (4 micrograms MKT-077/mg protein). Further,
      the data show a selective loss of mitochondrial DNA in CX-1 and CRL1420 cells
      (carcinoma) but not CV-1 cells (normal epithelial) treated with 3 microgram/ml
      MKT-077 for up to 3 days. Under the same conditions, nuclear DNA was unaffected
      in all three cell lines. The sensitivity of the cell lines tested to
      mitochondrial damage by MKT-077 correlates well with their sensitivity to
      cytotoxicity by MKT-077. These results demonstrate selective mitochondrial damage
      by MKT-077 at the cellular, biochemical, and molecular levels and suggest that
      selective effects on mitochondrial structure and function may provide a basis for
      the selective malignant cell killing exhibited by this compound.

PMID- 8564970
TI  - In vivo administration of MKT-077 causes partial yet reversible impairment of
      mitochondrial function.
AB  - The effects of in vivo administration of a pharmacologically toxic dose of the
      lipophilic cationic compound, MKT-077, were investigated in selected vital organs
      of the rat. MKT-077 (15 mg/kg body weight), administered by bolus i.v. injection
      every day for 5 days, did not detectably influence rat heart and kidney
      mitochondrial respiration. Although the same dosage of MKT-077 significantly
      decreased respiratory rates in rat liver mitochondria relative to untreated
      controls, complete recovery was evident within 3 days following drug withdrawal.
      Whereas the mitochondrial DNA of rat kidney and liver appeared to be unaffected
      by MKT-077 treatment, levels of heart mtDNA were noticeably less than control
      levels in the immediate interval following drug administration. However, this
      latter effect was partially reversed as early as 10 days following treatment and
      completely reversed within a 30-day posttreatment period. These results strongly
      suggest that a pharmacologically toxic dose of MKT-077 minimally affects the
      overall functional integrity of mitochondria in such critical, although highly
      vulnerable, tissues as the heart, liver, and kidney.

PMID- 8564971
TI  - Association between cisplatin resistance and mutation of p53 gene and reduced bax
      expression in ovarian carcinoma cell systems.
AB  - P53 status may be a determinant of chemosensitivity of tumor cells; however, its
      involvement in cellular resistance to cisplatin remains uncertain. To investigate
      the relationships between p53 and the development of resistance to cisplatin, the
      p53 gene status was studied in ovarian carcinoma cell systems which included two
      cisplatin-resistant variants (IGROV-1/Pt 0.5 and IGROV-1/Pt 1) selected in vitro
      after prolonged drug exposure of the cisplatin-sensitive parental IGROV-1 cell
      line. IGROV-1/Pt 0.5 and IGROV-1/Pt 1 cell lines exhibited a degree of resistance
      of approximately 6 and 14, respectively, following 96-h exposure to the drug and
      were cross-resistant to other DNA-damaging agents (ionizing radiation and
      melphalan). Resistance to cisplatin paralleled a reduced cell susceptibility to
      cisplatin-induced apoptosis. DNA single-strand conformation polymorphism analysis
      of exons 5-9 demonstrated the presence of two mutants alleles at exon 8 in the
      two resistant cell lines, in contrast to the parental IGROV-1 cell line which
      exhibited the wild-type p53 gene. Direct DNA sequencing revealed that the
      mutations consist of two nucleotide changes in the DNA-binding domain at codons
      270 (T/A) and 282 (C/T). The consecutive levels of p53 protein were lower in
      IGROV-1 than in IGROV-1/Pt cells. Following exposure to ionizing radiation or
      cisplatin, accumulation of the p53 protein was markedly enhanced only in the
      sensitive cells. Concomitantly, the expression of WAF-1 protein was strongly
      induced in the parental IGROV-1 cells, whereas WAF-1 protein remained
      undetectable in the IGROV-1/Pt 1 subline after DNA-damaging treatment. Consistent
      with this finding is the observation that ionizing radiation caused a different
      pattern of cell cycle perturbation in sensitive and resistant cells. Northern
      blot analysis demonstrated a marked reduction in bax mRNA levels in IGROV-1/Pt 1
      cisplatin-resistant cells. Cotransfection assays with wild-type or mutant p53
      expression plasmids and a reporter gene plasmid that utilized the bax gene
      promoter to drive transcription of chloramphenicol acetyltransferase were
      consistent with the role of p53 in regulation of bax expression in these cells.
      Taken together, these observations support a role for mutations of the p53 gene
      in the development of cisplatin resistance in ovarian cancer as a consequence of
      loss of the ability of p53 to transactivate bax, an apoptosis-inducing gene.

PMID- 8564972
TI  - Hyperthermia enhances tumor uptake and antitumor efficacy of thermostable
      liposomal daunorubicin in a rat solid tumor.
AB  - The combination of local hyperthermia (HT) with thermostable liposomal
      daunorubicin (DaunoXome, DX) was investigated to assess targeted drug delivery to
      experimental tumors. Female Wag/Rij rats bearing solid R-1 rhabdomyosarcomas
      received i.v. injections of 10 or 15 mg/kg of DX or free-Daunorubicin (f-Dau).
      After a 1-h interval, HT (60 min at 43 degrees C) was applied. Pharmacokinetics
      were studied in relation to tumor growth time (TGT), i.e., the time for tumors to
      reach their original volumes. Pharmacokinetic studies revealed that DX
      accumulation in tumor tissue was similar to f-Dau. A 5.4-fold increase (P =
      0.0084) in tumor drug delivery was observed when DX was combined with HT, whereas
      liposomes remained stable. For f-Dau, HT had an additional effect on TGT at both
      drug doses tested (9.6 and 6.2 days, respectively, for 10 mg/kg, P = 0.0092; 17.7
      and 13.7, respectively, for 15 mg/kg, P = 0.0431). For DX, HT significantly
      enhanced TGT of DX in the lower dose (17.1 and 6.4 days, respectively, P =
      0.0005), whereas tumors did not regrow at day 25 after DX + HT in the higher
      dose. Unfortunately, after this time interval, the animals died of late toxicity,
      probably not related to HT. These results indicate that HT promotes extravasation
      of DX into tumor tissue and enhances its effectiveness. The finding that HT
      induced drug release from the liposomes was not responsible for enhanced
      antitumor activity provides a rationale for further investigation of thermostable
      liposomes in conjunction with HT.

PMID- 8564973
TI  - Clinical investigation of a cytostatic calcium influx inhibitor in patients with
      refractory cancers.
AB  - Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium
      channels that reversibly inhibits angiogenesis, tumor cell proliferation, and
      metastatic potential. Inhibition of calcium influx and calcium-dependent events
      is a potential common mechanism underlying these effects of CAI. The cytostatic
      and antiangiogenic properties of CAI led to its development for clinical
      investigation. In a Phase I clinical trial open to patients with refractory solid
      tumors, 49 patients received p.o. administered CAI daily or every other day. Two
      oral formulations, PEG-400 CAI solution and a gelatin capsule containing CAI in
      PEG-400, were tested. All administered dosages of CAI yielded plasma
      concentration at or above the range demonstrated to be effective in inhibiting
      signaling and cancer progression in vitro and in preclinical models (1
      microgram/ml, 2.3 microM). Toxicity of p.o. administered CAI most commonly
      consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia.
      CAI administration at bedtime ameliorated gastrointestinal complaints in many
      patients; others required addition of simple antiemetic regimens, usually
      consisting of metoclopropamide or prochlorperazine. Gastrointestinal complaints
      were the cause for compliance-limiting toxicity at 175 mg/m2/day of the liquid
      formulation and 125 mg/m2/day of the gelatin capsule formation. Reversible and
      rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1
      patient) were dose-limiting toxicities observed at the 330 mg/m2 every-other-day
      liquid CAI dose level. No evidence of cumulative end organ damage or central
      nervous system injury was observed. Disease stabilization and improvement in
      performance status was observed. Disease stabilization and improvement in
      performance status was observed in 49% of evaluable patients who had disease
      progression before CAI. Disease stabilization and associated improvement in
      performance status was seen in patients with renal cell carcinoma (7 months),
      pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian
      cancer (7 months), and non-small cell lung cancer (3 months). The recommended
      Phase II doses from this trial are 150 mg/m2/day in the liquid formation and 100
      mg/m2/day in the gelatin capsule formation.

PMID- 8564974
TI  - Reversal of multidrug resistance in vivo by dietary administration of the
      phytochemical indole-3-carbinol.
AB  - A major obstacle to successful chemotherapy is the development of multidrug
      resistance (MDR) by cancer cells. MDR is characterized by enhanced cellular
      efflux of many structurally and functionally diverse compounds, including many
      anticancer drugs, due to overexpression of the MDR-1 gene product, P
      glycoprotein. We hypothesized that the phytochemical, indole-3-carbinol (I3C),
      and some of its acid-condensation derivatives may inhibit P-glycoprotein-mediated
      transport due to their aromatic and nitrogen components, thus increasing the
      accumulation and efficacy of anticancer drugs and acting as a dietary adjuvant to
      conventional chemotherapy. I3C was subjected to acid conditions similar to those
      occurring in the stomach following ingestion and three acid-condensation
      products; a dimer, a noncyclic trimer, and a cyclic trimer were isolated and
      purified by high-performance liquid chromatography. The ability of I3C and its
      acid-condensation derivatives to reverse MDR was investigated using murine B16
      melanoma cells that were transfected with the human MDR-1 gene (B16/hMDR-1 cells)
      and were cross-resistant to vinblastine and doxorubicin. The I3C acid
      condensation product mixture, but not I3C, sensitized B16/hMDR-1 transfectants to
      the toxicity of vinblastine and doxorubicin. All three I3C acid-condensation
      products also increased the accumulation of the P-glycoprotein substrate,
      doxorubicin, in B16/hMDR-1 transfectants to levels comparable to parental B16
      cells. The I3C acid-condensation product mixture competed with azidopine for
      binding to P-glycoprotein, suggesting that the observed MDR-reversing effect of
      the acid-condensation products was due to direct interaction with P-glycoprotein.
      The ability of p.o. administered I3C to reverse MDR was also tested in vivo. The
      resistance of B16/hMDR-1 transfectants to vinblastine and doxorubicin was
      preserved after i.p. injection and growth in nude mice. Tumor mass in mice that
      were provided with 333 or 500 mg/kg mouse/day I3C in their diet and injected s.c.
      with the anticancer drugs doxorubicin or vinblastine was significantly reduced as
      compared to tumor mass in mice provided with standard diet and injected with
      these anticancer drugs or mice provided with 500 mg/kg mouse/day I3C and not
      injected with anticancer compound. The concentrations of I3C used had no effect
      on survival or the general appearance and behavior of the mice. Collectively,
      these results indicate that ingestion of the common dietary constituent I3C
      results in its conversion to acid-condensation derivatives that sensitized MDR
      tumors to chemotherapeutic drugs without eliciting direct toxicity to the host.

PMID- 8564975
TI  - Occasional memory cytotoxic T-cell responses of patients with human
      papillomavirus type 16-positive cervical lesions against a human leukocyte
      antigen-A *0201-restricted E7-encoded epitope.
AB  - Most cervical carcinoma (Cxca) cells constitutively express human papillomavirus
      type 16 (HPV16) E6 and E7 oncoproteins. These proteins are, therefore, attractive
      targets for T cell-based immunotherapy. Previously, we identified HVP16 E7
      encoded CTL epitopes. In patients with cervical intraepithelial neoplasia or
      Cxca, little is known concerning T-cell activity against viruses in general and
      against HPV16 in particular. Here, we have screened the blood of 10 healthy donor
      controls and of 22 patients with HPV16+ cervical lesions for the presence of CTLs
      directed against HPV16 E7- and control influenza virus matrix-derived epitopes
      presented by HLA-A *0201. We detected influenza virus-specific CTLs in all donors
      and in the majority of patients, indicating that most patients have functioning T
      cell responses despite their lesions or therapeutic interventions. Moreover, we
      show that patients with HPV16+ lesions occasionally have memory CTLs against a
      HPV16 E7-encoded epitope (sequence YMLD-LQPETT), providing evidence for natural
      CTL immunity against HPV16 in patients with cervical lesions. Combined, these
      findings raise possibilities for vaccination with HPV16 E7-encoded peptides to
      induce or augment CTL responses for treatment or prevention of Cxca.

PMID- 8564976
TI  - Allelotypes of primary cutaneous melanoma and benign melanocytic nevi.
AB  - A multistep genetic model of tumorigenesis, based on genetic alterations in
      benign and primary malignant lesions, has been proposed for neoplasms such as
      colonic carcinoma. However, evidence for a similar genetic progression in
      melanoma has relied heavily on findings in cultured lesions or metastases. We
      have investigated every autosomal arm for loss of heterozygosity in 41 primary
      cutaneous melanomas and 32 benign melanocytic nevi, and have investigated several
      chromosome arms that show loss in melanoma in 27 Spitz nevi (a nevus with
      histological similarities to melanoma). Loss of heterozygosity in primary
      melanoma was identified most frequently on chromosomes 9p (46%) at loci near the
      p16INK4 gene, 10q (31%), 6q (31%), and 18q (22%); loss of these chromosome arms
      were related to the progression of the melanoma. Only two benign melanocytic nevi
      (both of which showed atypical features on histology) demonstrated genetic
      alterations, including p9 loss in one case. In addition, two Spitz nevi contained
      interstitial deletions on chromosome 9p. Our findings show that loss of
      heterozygosity of 9p is not confined to melanoma, but that other uncultured
      melanocytic lesions can also display loss of this chromosome arm, and that other
      genetic changes (e.g., loss of 10q, 6q, and 18q) may be important in conveying
      the malignant phenotype to melanoma.

PMID- 8564977
TI  - Defective transfer RNA-queuine modification in C3H10T1/2 murine fibroblasts
      transfected with oncogenic ras.
AB  - tRNA isoacceptors for aspartic acid, asparagine, histidine, and tyrosine are
      modified in the anticodon wobble position with the deazaguanine analogue queuine.
      Queuine modification is defective in many tumors and transformed cell lines, and
      the extent of hypomodification correlates with staging and outcome in numerous
      human tumors. The molecular role of queuine modification in normal cells and the
      mechanisms of queuine hypomodification in tumors are unknown. We have
      characterized nontransformed C3H10T1/2 murine fibroblasts (C3H) and their ras
      transfected counterparts (RasC4) with respect to the causes and effects of
      queuine hypomodification. RasC4 cells are hypomodified for queuine compared with
      C3H cells, despite increase tRNA-guanine ribosyltansferase activity. Excess
      exogenous queuine can cause repletion of tRNA queuine levels in RasC4 cells.
      Queuine modification of both C3H and RasC4 cells can be decreased by treatment
      with 7-methylguanine. This treatment does not affect growth in monolayer culture
      but enhances anchorage-independent growth of RasC4 cells greatly. These cell
      lines may be useful systems for the study of queuine function in normal cells and
      the causes and consequences of hypomodification for queuine in tumors.

PMID- 8564978
TI  - Genomic localization of novel candidate tumor suppressor gene loci in human
      parathyroid adenomas.
AB  - Only one oncogene, cyclin D1/PRAD1, has an established role in parathyroid
      tumorigenesis, and parathyroid tumor suppressor genes on chromosome arms 1p and
      11q, which still have not been identified, have also been implicated by loss of
      heterozygosity analysis. To investigate whether other putative tumor suppressor
      genes are involved in the pathogenesis of parathyroid adenomas, we performed a
      more comprehensive analysis of allelic losses in these tumors. Using 39
      polymorphic markers, we examined each chromosome arm, excluding the short arms of
      the acrocentric chromosomes. In 25 parathyroid adenomas, frequent loss of
      heterozygosity, in > 25% of the informative cases, was observed on chromosome
      arms 6q (30%), 11p (27%), and 15q (35%), in addition to previously reported 1p
      (30%) and 11q (38%) allelic losses. To more specifically localize the smallest
      shared regions of molecular genetic deletion, we examined the following
      chromosomes in greater detail: chromosome 6 (9 additional markers), chromosome 11
      (8 additional markers), and chromosome 15 (15 additional markers). The regions
      most commonly deleted in these tumors were 6q22-23, 6q26-27, 11q13, 15q11-21, and
      15q26-qter. All tumors with 11p loss had patterns consistent with monosomy for
      chromosome 11. These findings provide novel evidence for the existence of tumor
      suppressor genes on chromosome arms 6q and 15q that contribute commonly to the
      pathogenesis of parathyroid adenomas.

PMID- 8564979
TI  - Allelic deletion on chromosome 17p13.3 in early ovarian cancer.
AB  - Multiple chromosome 17 loci may be involved in ovarian carcinogenesis. Fifty
      seven sporadic ovarian epithelial tumors were examined for loss of heterozygosity
      at 15 loci on chromosomes 17p. Eighty % (39 of 49) of informative tumors had
      allelic loss in 17p13.3 at D17S30, D17S28, or both loci within this region,
      including 3 of 7 tumors of low malignant potential and 4 of 5 nonmetastatic
      carcinomas. The smallest region of overlapping deletions extends from D17S28 to
      D17S30, a distance of 15 kb. Furthermore, several tumors have breakpoints within
      the region detected by the D17S30 probe. Chromosome 17p13.3 genes with potential
      tumor suppressor function include HIC-1, DPH2L (N. J. Phillips et al. Isolation
      of a human diphthamide biosynthesis gene on chromosome 17p13.3, submitted for
      publication)/OVCA1, PEDF, and CRK. The HIC-1 coding sequence lies i kb
      centromeric to the D17S28-S17S30 region of deletion (M. Makos Wales et al., Nat.
      Med., 1:570-577, 1995) but remains a candidate because 5'-regulatory elements may
      lie within the critical region. Portions of the DPH2L/OVCA1 coding sequence lie
      within the D17S28-D17S30 interval. Somatic cell hybrid analysis places PEDF in an
      interval including D17S28, D17S30, and D17S54, whereas CRK is excluded from this
      interval. Chromosome 17p13.3 loss precedes TP53 and BRCA1 region deletions
      because the latter changes are see only in high-stage carcinomas. Microsatellite
      instability plays only a minor role in sporadic ovarian carcinogenesis because
      only 1 of 57 tumors showed this finding.

PMID- 8564980
TI  - Two distinct regions of deletion on the long arm of chromosome 5 in
      differentiated adenocarcinomas of the stomach.
AB  - Frequent loss of heterozygosity (LOH) on the long arm of chromosome 5 (5q) has
      been reported in many types of human malignancies, including gastric carcinoma.
      One of the targets of 5q-LOH in colorectal carcinoma is certainly the adenomatous
      polyposis coli (APC) gene on 5q21. However, other evidence has suggested the
      presence of another tumor suppressor gene in this region which may be inactivated
      in gastric carcinoma. In the present study, to determine the location of the
      putative tumor suppressor gene on 5q, LOH at nine microsatellite loci on 5q were
      investigated at 38 differentiated adenocarcinomas of the stomach that probably
      did not carry APC mutations. LOH at any locus on 5q occurred in 37% (14 of 38) of
      the tumors. Although many tumors exhibited large interstitial deletions on 5q
      that included the APC locus (5q21), we have identified minimum regions of
      deletion as the D5S428 locus and the interferon regulatory factor-1 (IRF-1)
      locus. Thus, at least two putative tumor suppressor genes, which play a crucial
      role in the genesis of differentiated adenocarcinoma of the stomach and are
      distinct from the APC gene, lie on 5q.

PMID- 8564981
TI  - Expression of prokaryotic HhaI DNA methyltransferase is transforming and lethal
      to NIH 3T3 cells.
AB  - In neoplastic cells, levels of DNA methyltransferase activity are often
      increased, and evidence is accruing to suggest an important role for this event
      in tumorigenesis. To evaluate this possibility further, and to investigate the
      contribution of increasing de novo, as opposed to maintenance, DNA methylation in
      mammalian cells, we expressed the bacterial HhaI methyltransferase in cultured
      murine fibroblasts. This enzyme is a pure de novo DNA methyltransferase that
      methylates the internal C in the sequence GCGC. We find that both constitutive
      and induced expression of the wild-type HhaI results, primarily, in lethality to
      the cells. However, surviving cell clones that express low levels of M. HhaI
      demonstrate increased tumorigenicity as assessed by soft agar cloning efficiency
      (8.6% for sense HhaI-transduced PA 317 cells versus 0.4% for antisense controls;
      1.7% for sense HhaI-transfected NIH 3T3 cells versus 0% for a mutant HhaI
      control) and tumorigenicity in nude mouse heterotransplants (75% for sense HhaI
      transduced PA 317 cells versus 18.5% for antisense controls). DNA isolated from
      the clonogenic sense HhaI clones, versus clones expressing the mutant HhaI gene,
      has no increase in overall CpG methylation but an average of 27% (range, 16.7
      38.9) increase in methylcytosine content at GCGC sites. These findings suggest
      that eukaryotic cells tolerate a narrow window of increase de novo DNA
      methylating capacity, above which cell death occurs and within cell
      transformation results. Our results further emphasize the potential role of
      increased DNA methyltransferase activity in the evolution of cancer.

PMID- 8564982
TI  - Antiproliferative responses to two human colon cancer cell lines to vitamin D3
      are differently modified by 9-cis-retinoic acid.
AB  - 1 alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3] exerts antiproliferative actions in
      colorectal cancer, but their underlying molecular mechanisms have not been
      determined. 1,25(OH)2D3 regulates target gene transcription via a specific
      nuclear vitamin D receptor (VDR), which mediates hormone action preferentially as
      a heterodimer with 9-cis-retinoic acid receptors (RXRs). We investigated the
      actions of 1,25(OH)2D3 and 9-cis-retinoic acid (RA) in two human colon cancer
      cell lines, HT-29 and Caco-2. Both expressed mRNAs encoding VDR, RXR alpha, and
      RXR gamma, and VDR was regulated posttranscriptionally in Caco-2 cells. There was
      an antiproliferative response of both cell lines to 1,25(OH)2D3. 9-cis-RA exerted
      antiproliferative effects on Caco-2 cells but blocked 1,25(OH)2D3 actions in HT
      29 cells. The 1,25(OH)2D3-responsive gene 25-hydroxyvitamin D3 24-hydroxylase was
      induced in both cell lines b 1,25(OH)2D3 but in only HT-29 cells by 9-cis-RA.
      1,25(OH)2D3 and 9-cis-RA cotreatment enhanced 24-hydroxylase expression in HT-29
      cells only. The 24-hydroxylase enzyme is known to result in catabolism of
      1,25(OH)2D3 and attenuation of its actions. Increased 24-hydroxylase activity in
      HT-29 cells, but not in Caco-2 cells, in response to 9-cis-RA may account for
      some of the complex cell-specific responses demonstrated in these studies.

PMID- 8564983
TI  - Human amniotic tumor that induces new bone formation in vivo produces growth
      regulatory activity in vitro for osteoblasts identified as an extended form of
      basic fibroblast growth factor.
AB  - Tumors occasionally stimulate bone formation and cause osteoblastic metastases.
      Although this occurs most frequently in widespread prostate cancer, human
      prostate cancer cells are difficult to grow in culture without changing their
      phenotype, and the few available prostatic cancer lines do not increase bone
      formation in vivo. To identify tumor-derived osteoblast-stimulatory factors, we
      studied a long-established human tumor cell line derived from human amnion that
      has, in the past, been reported to cause bone formation in vivo when inoculated
      into nude mice. Tumor cells were inoculated into nude mice and induced extensive
      new bone formation. To characterize osteoblast growth factors produced by these
      tumor cells, solid tumor was isolated from the mice and extracted at neutral pH.
      Biological activity, assessed by stimulation of proliferation of MG-63 osteoblast
      like cells, was used to monitor purification after heparin-Sepharose column
      chromatography, Mono-S, and C4 reverse-phase high-performance liquid
      chromatography. An extend amino-terminal form of basic fibroblast growth factor
      (FGF) was purified by its capacity to stimulate proliferation in MG-63 cells and
      partially sequenced. Basic FGF is also known to stimulate proliferation in MG-63
      cells and other osteoblasts in vitro and bone formation in vivo. In summary,
      these human tumor cells stimulate new bone formation in vivo and produce an
      osteoblast stimulating activity in vitro, which has been identified as a form of
      basic FGF.

PMID- 8564984
TI  - Activation of stress-activator protein kinase/c-Jun N-terminal kinase by the non
      TPA-type tumor promoter palytoxin.
AB  - Previous studies have shown that structurally diverse tumor promoters can
      modulate protein kinases involved in signal transduction. In this study, we show
      that palytoxin, a potent non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type skin
      tumor promoter, induces a signaling pathway leading to the activation of the
      stress-activated protein kinases/c-Jun N-terminal kinases (JNK) in Swiss 3T3
      fibroblasts. Treatment of cells with doses as low as 0.1 mN palytoxin results in
      significant activation of JNK. In contrast to epidermal growth factor, which
      induces a transient activation of JNK in Swiss 3T3 cells, palytoxin causes
      prolonged enzyme activation. Since stimulation of ion flux appears to play an
      important role in the mechanism of action of palytoxin in other systems, we
      investigated the role of sodium and calcium in the activation of JNK: (a) our
      results show that incubation of Swiss 3T3 cells in a sodium-free medium
      dramatically reduced the magnitude of JNK activation by palytoxin; and (b) we
      found that the sodium ionophore gramicidin activates JNK. Together, these results
      suggest that sodium influx, which is a hallmark of palytoxin action, may play a
      key role in the activation of JNK by palytoxin. Our results indicate that calcium
      influx is not necessary or sufficient for palytoxin-induced activation of JNK. In
      contrast to palytoxin, the TPA-type tumor promoter phorbol 12,13-dibutyrate and
      the non-TPA-type tumor promoters thapsigargin and okadaic acid do not appear to
      activate JNK in this system. In contrast to phorbol 12,13-dibutyrate, palytoxin
      does not activate the p42/p44 mitogen-activated protein kinases. Our results
      demonstrate that Swiss 3T3 fibroblasts, palytoxin can activate a protein kinase
      signaling pathway that is distinct from that activated by the prototypical
      phorbol ester tumor promoters and other potent skin tumor promoters.

PMID- 8564985
TI  - Human telomerase RNA and telomerase activity in immortal cell lines and tumor
      tissues.
AB  - Telomerase activity has been detected in many human immortal cells lines and in
      tumor tissues, whereas it is generally absent from primary cell strains and from
      many tumor adjacent tissue samples. With the recently cloned human telomerase RNA
      (hTR), we used Northern analysis to follow the levels of hTR in primary,
      precrisis, and immortalized cells. It was surprising that the amount of hTR was
      high in cell strains that lacked telomerase activity, and the levels did not
      parallel the increases in telomerase activity, which accompanies immortalization.
      In addition, although the hTR levels were somewhat higher in tumor samples
      compared to nontumor tissues, the level of hTR in a variety of different human
      tumors did not predict the level of telomerase activity in the tumor. Thus,
      whereas hTR was detected in all samples that have telomerase activity, the
      presence of the RNA was not a good predictor of the presence or amount of
      telomerase activity.

PMID- 8564986
TI  - Association of elevated levels of hyaluronidase, a matrix-degrading enzyme, with
      prostate cancer progression.
AB  - Components of extracellular matrix and the matrix-degrading enzymes are some of
      the key regulators of tumor metastasis and angiogenesis. Hyaluronic acid (HA), a
      matrix glycosaminoglycan, is known to promote tumor cell adhesion and migration,
      and its small fragments are angiogenic. We have compared levels of hyaluronidase,
      an enzyme that degrades HA, in normal adult prostate (NAP), benign prostate
      hyperplasia (BPH) and prostate cancer (CaP) tissues and in conditioned media from
      epithelial explant cultures, using a sensitive substrate(HA)-gel assay and an
      ELISA-like assay. The results show a significant elevation (3-10-fold) of this
      enzyme in tumor tissues compared to that in NAP and BPH tissues. Furthermore, the
      hyaluronidase levels in tissues correlates well with the tumor grade. For
      example, the concentrations in a locally extended CaP lesion (191 +/- 7.9
      milliunits/mg protein), and low-grade tumors (9.4 +/- 1.4 milliunits/mg protein),
      respectively. Among the primary epithelial explant cultures, CaP cultures secrete
      at least 10-fold higher levels of hyaluronidase that those secreted by NAP and
      BPH cultures. Furthermore, among the established prostate cancer cell lines,
      DU145, an androgen-unresponsive metastatic line, secretes 4-fold more
      hyaluronidase than LNCaP, an androgen-responsive and relatively well
      differentiated cell line. We also show that prostatic hyaluronidase has an
      apparent M(r) approximate to 55,000, a pH optimum of 4.6, and is distinct from
      other well-characterized hyaluronidases.

PMID- 8564987
TI  - Palliative medicine. Problem areas in pain and symptom management. Introduction.

PMID- 8564988
TI  - Emesis and anti-emesis.
AB  - From a consideration of the above evidence, it is possible to hypothesize that
      the 5-HT3 receptors, which are located both in the gut and in the AP/NTS, may
      play an important and perhaps pivotal part in the mechanism(s) of action of
      chemotherapy and radiotherapy to induce emesis in animals and humans and
      represent the anti-emetic sites of action of ondansetron and related agents (see
      Fig. 1). The value of ondansetron and the 5-HT3 receptor antagonists has been to
      greatly improve the treatment of nausea and emesis in the cancer patient and to
      cause a renaissance in emesis research. The 5-HT3 receptor antagonists have
      helped to redefine the phases of chemotherapy induced emesis and establish the
      first clear neurotransmitter links in the emetic reflex. It has also encouraged
      the analysis of emetic mechanisms that will identify further points for
      pharmacological intervention that may ultimately provide "broad spectrum" anti
      emetic agents. Such compounds would further improve the quality of life and
      treatment of the cancer patient, leading to increased success in the treatment of
      malignant tumours.

PMID- 8564989
TI  - Current approaches to the management of constipation.
AB  - Constipation in patients with advanced cancer results from reduced food intake
      and debility as well as medication, particularly opioid analgesics. Prophylactic
      measures are important, but most patients will require laxatives. History and
      examination should exclude the presence of intestinal obstruction, and if there
      is doubt, only a softening laxative should be used. In general, a combination of
      softening and stimulant laxatives is most likely to be successful with minimum
      adverse effects. Management of constipation is frequently poor, and considerable
      research effort is needed into both the more effective use of current treatments
      and the development of new therapies.

PMID- 8564990
TI  - Intestinal obstruction.
AB  - Intestinal obstruction is a common and distressing complication for patients with
      advanced abdominal or pelvic cancer. Many of these patients are unfit for surgery
      due to extensive local disease or poor general condition. There are now many drug
      regimens available that will relieve obstructive symptoms in most patients,
      although a few, mainly with high obstruction, will require a venting procedure.

PMID- 8564991
TI  - Symptomatic management of HIV associated gastrointestinal disease.
AB  - This chapter describes the differential diagnosis and management of
      gastrointestinal symptoms associated with HIV infection. There is no clear point
      when management moves from intervention to palliation, and as with other
      manifestations of HIV disease, clinical decisions have to be guided by the wishes
      of the patient. In general, early diagnosis and treatment of HIV associated
      opportunistic infection are likely to keep patients symptom free, but when
      specific therapy is unavailable, unsuccessful or unwanted, then there is a clear
      indication to strive for symptom control using conventional palliative care.

PMID- 8564992
TI  - Incident pain.
AB  - Incident pain is a major problem for most patients with cancer pain. It is
      difficult to classify and poorly studied. The problem is that doses of opioids
      high enough to control episodic incident pain are too high when that pain is
      absent, leading to adverse effects. The commonest type of incident pain is pain
      on movement, leading to a quantitative increase in pain intensity. There is also
      a class of incident pain that is qualitatively different from any pain at rest,
      more akin to neuropathic pain. "Breakthrough" pain is the term used to describe
      pains that break through an existing analgesic regimen; these may be incident
      pains. There are no randomized controlled trials of incident pain management in
      cancer pain. The suggestions made for improving management are therefore based on
      such trials in other pain contexts. Studies in the cancer context will need to
      concentrate on characterizing the pain episodes.

PMID- 8564993
TI  - Pathogenesis and management of cancer associated hypercalcaemia.
AB  - Hypercalcaemia is the most common metabolic complication of malignant disease. It
      is an important cause of morbidity in cancer patients and is potentially
      amendable to treatment. Bone metastases are rarely the cause of hypercalcaemia in
      malignancy, the elevation in calcium concentrations usually resulting from the
      effects of humoral mediators released by the tumour. Many factors isolated from
      tumours have the potential to cause hypercalcaemia, but the most important is
      parathyroid hormone related protein (PTHrP), a peptide which mimics the effect of
      PTH. Treatment of cancer associated hypercalcaemia is based on an initial phase
      of volume repletion with isotonic saline, followed by drug treatment to inhibit
      bone resorption. Bisphosphonates are the most widely used agents in the treatment
      of such bone resorption, are very effective and have minimal toxicity. Gallium
      nitrate is also effective but less widely used. The combination of
      bisphosphonates and calcitonin has been found to be particularly useful in
      patients with severe hypercalcaemia, since this gives a more rapid reduction in
      serum calcium values than can be achieved with bisphosphonate alone. In the
      longer term, effective control of hypercalcaemia depends on treating the primary
      tumour. In the majority of cases this is not possible, however, because of the
      state of disease progression or the nature of the tumour. Anti-hypercalcaemic
      therapy is an important palliative measure in cancer patients who have symptoms
      of hypercalcaemia. Treatment does little to alter the long term prognosis but
      often results in an improvement in symptoms such that the majority may be made
      well enough to be discharged from hospital care.

PMID- 8564994
TI  - Paraneoplastic syndromes.
AB  - The paraneoplastic syndrome does exist and its manifestations are as old as
      malignancy itself. Progress in molecular pathology will help us to understand its
      origin. At the same time, each investigator is obliged to develop therapeutic
      means that can be offered to the cancer patient to overcome its painful and
      troublesome disorders.

PMID- 8564995
TI  - Pain and symptom control in paediatric palliative care.
AB  - Important differences become evident in a comparison of cancer pain between
      children and adults. Management of pain in children is commonly
      multidisciplinary, is less dependent on invasive measures and relies more on
      systemic therapy. Children are not little adults: their immaturity, developing
      cognition and dependence all influence their experience and interpretation of
      pain. Much progress has been made in altering practices such as under-prescribing
      and underdosing that have adversely affected adequate control of pain in
      children. The challenge for paediatric health care providers in the mid 1990s is
      not only to be informed of current practices in pain and symptom control in
      paediatric palliative care, but also to remember to establish those practices in
      day to day management. Even though pain and its effects in children are now
      better understood, it is often still not managed optimally. Good management of
      pain in children depends on accurate assessment. In the past 10 years, assessment
      of pain in children has advanced considerably. However, assessment of pain in the
      preverbal child is still inadequate and in need of attention. Sedation, tolerance
      and involuntary movements may occur as side effects of opioids in children and
      may cause significant problems in management of the dying child. Psychostimulants
      can diminish sedation to some extent, but there is little information as yet on
      the value of these drugs in children. Tolerance to opioids may develop quickly,
      leading to poor control of pain and distress for the child. Strategies to improve
      management of tolerance include use of regional anaesthetic techniques such as
      the epidural/intrathecal route for opioid administration. Involuntary movements
      induced by opioids are uncommon but have the potential to cause significant
      distress. The mechanisms underlying these side effects of opioids need to be
      established. Strategies are needed for the effective treatment and prevention of
      these side effects. Neuropathic pain can be severe, distressing and difficult to
      treat. Experience of its treatment in terminally ill children is limited.
      Effective use of tricyclic antidepressants and systemically administered local
      anaesthetics is still to be determined. Regional anaesthetic techniques may be of
      great benefit when neuropathic pain cannot be controlled with systemic therapy.
      Procedural pain is more common than pain related to disease in the management of
      paediatric cancer. Further research is needed to identify the best approach to
      its management. We have found nitrous oxide to be of great benefit in management
      of procedural pain in children. Non-pharmacological methods of treatment of pain
      in children, such as transcutaneous electrical nerve stimulation or acupuncture,
      may also be useful and should receive continuing evaluation. There are
      significant and current issues in paediatric palliative care besides management
      of pain. There are difficulties in the provision of home nursing care for
      children with cancer in the terminal phase of their illness, including lack of
      community nursing services at night and on weekends and lack of adequate home
      help for parents. Attitudes of staff involved in the care of the child and family
      and their commitment to working as a multidisciplinary team strongly influence
      the quality and success of care given. Pain control and palliative medicine are
      evaluable by measures of quality assurance or outcome, and adoption of such
      evaluations should improve standards of care. Euthanasia in children is even more
      difficult as an ethical dilemma than in adults. Optimum symptom control with
      current techniques should almost always obviate its consideration. We are opposed
      to euthanasia. Psychosocial and cultural issues all influence the family's
      experience of palliative care. Further research is necessary in all of these
      areas.(ABSTRACT TRUNCATED)

PMID- 8564996
TI  - Clinical audit and organizational audit in palliative care.
AB  - Palliative medicine has a history of critical appraisal dating back to the start
      of the hospice movement during the 1970s. Methods and audit tools are available
      and have been tested, especially for clinical audit. Practical approaches such as
      the Support Team Assessment Schedule, the Edmonton Symptom Assessment System and
      topic audits are particularly recommended. Developments in clinical audit could
      lead to clinical algorithms or protocols to assist patient management.
      Organizational audit is less well developed, and the scientific basis of choosing
      the standards is questioned. However, only with the piloting of organizational
      audits will their true value emerge. There are, however, constraints of time and
      resources: audit should be cost effective and in the future will need management
      and evaluation.

PMID- 8564997
TI  - Perspectives on opioid tolerance from basic research: behavioural studies after
      spinal administration in rodents.
AB  - For tolerance development studies, computer modelling and statistical tests
      suggested that the equation which best described the decrement of analgesic
      effect was best served by an exponential decay function. Further analysis of the
      time course data led to the tentative conclusion that all groups of animals
      became tolerant at the same rate, regardless of drug or dose. A literature search
      revealed then, as it does now, that although there are many statements regarding
      the rate of opioid tolerance, there has been little systematic investigation of
      this. The Holy Grail of obtaining the rates of tolerance for a number of opioid
      agents in a systematic study is well within grasp. This information will be
      needed in clinical practice for the rational choice of opioid with regard to rate
      of the development of tolerance. The working hypothesis that emerges for the
      magnitude of opioid tolerance is that more potent agonists produce less
      tolerance. Further confirmation of this hypothesis has been forthcoming. This
      suggests that clinical use of more potent opioids, such as fentanyl, should be
      considered as a substitute for morphine in long term treatment regimens. The
      working hypothesis for cross-tolerance is that agents acting on the same
      receptors will show cross-tolerance. Cross-tolerance will also be observed among
      agents acting on different receptors, but only those that exhibit pharmacological
      synergy after short term administration. Asymmetry of cross-tolerance can occur,
      as the magnitude of this cross-tolerance is determined by the relative potency of
      the toleragen with regard to that of the probe agent. Given the additional factor
      of receptor selectivity with agents of different receptor classes, types and
      subtypes, new studies need to be designed combining the toleragen with a
      selective antagonist to determine the precise receptor mediation of the magnitude
      of tolerance, and thus cross-tolerance. For example, the delta opioid DADLE
      infused with a mu selective opioid antagonist would produce an animal strictly
      tolerant at delta receptors, as DADLE has been implicated to have some effects at
      mu receptors. In any event, consideration of the quantitative measures of cross
      tolerance are extremely important to help shape a rationale treatment plan for
      patients who may become tolerant to a particular class of analgesics. In general,
      direct toleragen administration by constant dose, constant rate infusion into
      local central nervous system (CNS) regions will provide the most rigorous
      tolerance studies for examination of the pharmacodynamic theories of tolerance,
      as adaptations in processes affecting central bioavailability, such as
      dispositional changes in the blood-brain barrier or fibrous encapsulation of an
      implanted subcutaneous pellet, are circumvented. The above considerations also
      are relevant for studies of tolerance and cross-tolerance after
      intracerebroventricular administration or, in general, for tolerance studies
      after systemic administration. The possibility of probe administration to the
      same region of CNS that was rendered tolerant, as in the Y-catheter method,
      further enhances the focus on the pharmacodynamic mechanisms of tolerance without
      the ancillary and literally peripheral concerns of a dispositional nature. A
      posological approach to these studies cannot be overemphasized, as it is only
      through such time consuming and costly experiments that rigorous, quantitative
      data can be obtained. Such data may help to guide the hand of the physician
      towards rational therapeutic intervention in the treatment of patients with
      chronic pain and opioid tolerance.

PMID- 8564998
TI  - Tolerance to opioid analgesics: clinical aspects.
AB  - Tolerance is a complex phenomenon with important therapeutic implications.
      Understanding of its clinical aspects has been hampered by inadequate
      communication between clinicians, who have acquired striking observations
      relevant to the stability of the dose-response relationship in patients with
      pain, and investigators who have extensively studied animal models or drug
      effects in former addicts. In the clinical setting, it is now clear that the loss
      of analgesic effects over time has a differential diagnosis, only one component
      of which is tolerance. Evidence from a variety of sources suggests that true
      pharmacological tolerance to the analgesic effects of opioids is an uncommon
      cause for the need to escalate the opioid dose to maintain analgesic effects.
      Tolerance to non-analgesic effects appears to occur more reliably, but this
      phenomenon, too, is neither uniform nor simple. Some patients who appear to have
      developed tolerance to these adverse effects demonstrate a remarkable lack of
      tolerance when the pain is eliminated by some unrelated mechanism. The disparity
      between these clinical observations and the experimental literature on tolerance
      suggests that mechanisms related to the pain itself may have an important
      modulating effect on these phenomena. From the clinical perspective, the
      disparity emphasizes the need to avoid generalization from the laboratory to the
      clinic without adequate confirmation.

PMID- 8564999
TI  - Neurophysiology of opioid poorly responsive pain.
AB  - This review has covered the five potential causes for opioid poorly responsive
      pain, namely (a) a loss of opioid receptors on the spinal terminals of C-fibres
      as a result of peripheral nerve damage, (b) an accumulation of morphine-3
      glucuronide, (c) changes in the non-opioid peptides, F8Fa or CCK, either spinally
      or supraspinally, (d) actions of the opioid peptide dynorphin and (e) spinally
      generated hypersensitive states via activation of the NMDA receptor. The loss of
      opioid receptors is likely to be important where peripheral nerve pathology or
      compression occurs, but the evidence suggests that increasing the dose will
      overcome the reduced opioid response. Morphine-3-glucuronide is unlikely to be a
      factor, nor is dynorphin, but the endogenous peptides CCK and F8Fa may be
      important. Finally, there is an association between the NMDA receptor and
      hyperalgesia/allodynia and reduced opioid sensitivity. Dextrorphan and ketamine
      reduce NMDA mediated events and so are available to test this hypothesis.

PMID- 8565000
TI  - The cognitive and psychomotor effects of opioid drugs in cancer pain management.
AB  - The time has come to evaluate critically our practice of cancer pain management
      and the assumptions on which it is based. We owe it to our patients to maximize
      the quality of their lives and to provide evidence for them that is based on a
      scientific approach rather than anecdotal experience. From the information
      available, opioids do have effects on cognitive and psychomotor function, and
      although many of these effects diminish once the patient is on a stable dose, the
      evidence suggests that baseline pretreatment levels are not achieved. In
      addition, the relationship between measurable effects and the performance of
      everyday tasks such as driving is unclear. The challenge we now face is to
      continue the improvements in cancer pain control achieved over the last 25 years.
      The management of the central adverse effects of opioids must be focused on
      accurate assessment and careful titration of opioids against pain. Adjuvant
      analgesic drugs and non-drug measures should be used whenever possible, and drugs
      should be chosen that will not contribute to existing difficulties. The
      appropriate use of psychostimulants has yet to be established as has the relative
      benefit of one opioid over another in cancer pain.

PMID- 8565001
TI  - The therapeutics of dyspnoea.
AB  - In summary, our current understanding of the therapeutics of dyspnoea is
      inadequate and leaves plenty of room for improvement. Rationalization of the
      management of this symptom has the potential to improve the quality of life of
      countless patients with both malignant and non-malignant disease. To date,
      research studies addressing this issue are sparse. Those that have been conducted
      are incomplete in that almost all have assessed only the effect of single dose
      interventions in normal volunteers or patients with COPD. There is no information
      on either long term dosing with these drugs or their use in patients with cancer
      related breathlessness. It is possible that other pharmacological agents that
      have never been used for this indication may have therapeutic potential. The
      pharmacological treatment of breathlessness deserves further investigation, and
      clinical studies should be conducted in parallel with appropriate laboratory
      studies. Drug therapy is, however, but one aspect of the overall management of
      any symptom, and a thorough assessment of the role of non-drug interventions for
      dyspnoea is also essential. Well designed multicentre studies are urgently
      required to evaluate the symptomatic treatment of breathlessness, but such
      studies must be preceded by the development of valid and sensitive patient rated
      tools to assess this distressing and common symptom.

PMID- 8565002
TI  - Anorexia and cachexia in advanced cancer patients.
AB  - Cachexia is a frequent and devastating complication of advanced cancer. Current
      understanding of the pathophysiology of this syndrome implicates tumour induced
      metabolic changes and immune responses. Clinical manifestation include anorexia,
      chronic nausea, asthenia and change in body image. Aggressive nutritional
      intervention has not been shown to be of benefit. Patients and families should be
      counselled about the goals of nutritional intake. In selected cases, enteral
      nutrition may be appropriate. Pharmacological management should first be directed
      at correcting nausea. Agents of potential usefulness in the treatment of anorexia
      include corticosteroids, megestrol acetate, cyproheptadine, hydrazine sulphate
      and dronabinol. Future research should further address pathophysiology,
      symptomatic and metabolic effects of interventions and interactions with other
      syndromes of terminal cancer.

PMID- 8565003
TI  - A comparison of the conformation of sucrose octasulfate, free and bound to acidic
      fibroblast growth factor.
AB  - The conformation of sucrose octasulfate free in solution has been determined
      based on high-resolution NMR spectroscopy. Three-bond 1H-1H scalar coupling
      constants, laboratory and rotating frame NOEs, long-range 1H-13C scalar coupling
      constants, and chemical-shift temperature and ionic-strength dependence were
      used, aided by molecular mechanics calculations. By modification of a pulse
      sequence designed for measuring long-range 1H-13C coupling constants, it was
      possible to obtain an accurate value for the 3JC2f-H1g despite the confounding
      presence of 3JHH of similar value. Free sucrose octasulfate appears to assume a
      conformation significantly different from any of the eight conformations observed
      bound to acidic fibroblast growth factor, as determined in a previous X-ray
      crystallographic study [X. Zhu, B.T. Hsu, and D.C. Rees, Structure, 1 (1993) 27
      34]. Strong electrostatic interactions between guest and host may be the dominant
      factor in deformation of sucrose octasulfate. The implications of this study for
      protein-carbohydrate interactions and the effects of the presence of sulfate
      groups on the flexibility of sucrose are also discussed.

PMID- 8565004
TI  - Determination by NMR spectroscopy of the structure and conformational features of
      the enterobacterial common antigen isolated from Escherichia coli.
AB  - Complete 1H and 13C spectrum of a polysaccharide isolated from Escherichia coli,
      which is the major component of the enterobacterial common antigen, has been
      analyzed through two-dimensional nuclear magnetic resonance spectroscopy. In
      addition, distance constraints from NOESY and ROESY experiments have been
      combined with molecular dynamic simulations to determine its major conformation
      in water solution. Data resulting from both free dynamic simulations and
      restrained dynamic simulations have been compared with experimental data and
      discussed.

PMID- 8565005
TI  - Structural analysis of antiviral sulfated alpha-D-(1-->3)-linked mannans.
AB  - The structures of two alpha-(1-->3)-alpha-D-xylo-mannans were determined. The
      different antiviral activity of the xylo-mannans from Nothogenia fastigiata was
      explained on the basis of a flexible backbone, molecular size, content and
      distribution of sulfate groups and of the single stubs of beta-(1-->2)-linked D
      xylose.

PMID- 8565006
TI  - Structure of the O-specific polysaccharide of Hafnia alvei 1204 containing 3,6
      dideoxy-3-formamido-D-glucose.
AB  - The O-specific polysaccharide of Hafnia alvei strain 1204 has a hexasaccharide
      repeating unit containing D-mannose, D-glucuronic acid, 2-acetamido-2-deoxy-D
      glucose, 2-acetamido-2-deoxy-D-galactose, and 3,6-dideoxy-3-formamido-D-glucose
      (Qui3NFo) in the ratios 2:1:1:1:1 as well as O-acetyl groups. On the basis of
      methylation analysis of the intact, carboxyl-reduced, and Smith-degraded
      polysaccharide as well as 1D and 2D NMR spectroscopy, including 1D total
      correlation spectroscopy, 1D NOE spectroscopy, 2D homonuclear shift-correlated
      spectroscopy (COSY), and 13C,1H heteronuclear COSY, the following structure of
      the O-deacetylated polysaccharide was established: -->3)-alpha-D-Manp-(1-->2)
      alpha-D-Manp-(1-->3)-beta-D-GlcpN Ac-(1--> -->2)-beta-D-Quip3NFo-(1-->3)-alpha-D
      GalpNAc-(1-->4)-alpha-D-G lcpA-(1--> Location of the N-formyl group, occurring as
      two stereoisomers in the ratio approximately 3:1, was determined by an NOE on H-3
      Qui3N arising on pre-irradiation of HCO of the minor (E) isomer. The O-acetyl
      groups are attached in nonstoichiometric amounts at position 3 of GlcA and
      position 6 of a mannose residue or GlcNAc.

PMID- 8565007
TI  - Structure of the capsular polysaccharide from the Klebsiella K8 reference strain
      1015.
AB  - The structure of the capsular polysaccharide from the Klebsiella K8 reference
      strain 1015 has been elucidated. The structure was deduced from sugar analysis,
      different methylation analyses, a uronic acid degradation, and NMR spectroscopy.
      It is concluded that the polysaccharide is composed of pentasaccharide repeating
      units with the structure: [formula: see text] The structure differs from that of
      the previously published structure of the capsular polysaccharide from Klebsiella
      K8, which originates from another strain and has the following structure:
      [formula: see text] The serological similarity between the two strains is most
      likely derived from a common tetrasaccharide which is substituted in different
      ways in the two strains. Since the strain in the present investigation originates
      from the Klebsiella K reference strain collection of the International
      Escherichia and Klebsiella Centre, Copenhagen, Denmark, it is suggested that it
      should keep the designation K8. The other polysaccharide with Klebsiella K8
      specificity should be renamed as K8,52,59 based on the cross-reactivity of the
      strain (I. Orskov, unpublished).

PMID- 8565008
TI  - Purification of commercial gellan to monovalent cation salts results in acute
      modification of solution and gel-forming properties.
AB  - Lithium, sodium, potassium, and ammonium salts of the industrial polysaccharide
      gellan were prepared. The salts were freely soluble in water at room temperature
      (25 degrees C). The opinion had been generally held that heating to 100 degrees C
      was necessary for gellan to achieve complete solubility in the presence of mono-
      or multivalent cations. Then, upon cooling, the solutions would form gels. These
      conclusions were based on the properties imposed upon gellan samples by the
      presence of contaminating divalent cations. Commercial gellan samples contain
      calcium and magnesium at levels exceeding 0.9%, sufficient for counterion
      formation with over one-third of gellan's carboxyl groups. Purification was rapid
      and included sequential treatments with a cation-exchange (H+) resin, LiOH, NaOH,
      KOH, or NH4OH, and an anion-exchange (Cl-) resin. About 95% of the divalent
      cations and nearly 90% of the phosphate that contaminated commercial gellan were
      removed. The purified monovalent salts of gellan set in the presence of divalent
      cations and provide well-defined agents for gelling media used for propagation of
      microbes and plants. In a manner analogous to sodium alginate, solutions of
      lithium, sodium, potassium, or ammonium gellanate form beads when dropped into
      solutions of divalent cations. This property was exploited for entrapment of
      enzymes and cells in beads.

PMID- 8565009
TI  - Structural investigation of cell-wall polysaccharides from Neosartorya:
      relationships with their putative anamorphs of Aspergillus.

PMID- 8565010
TI  - The evolving paradigm of hypertension.
AB  - Although it is convenient to think of hypertension in its renal, epidemiologic,
      and vascular eras, a new perspective is rapidly coming to the forefront. As we
      become more critical in evaluating the performance of our health care systems, it
      is obvious that the major problems in hypertension do not lie entirely with
      unsolved problems of physiology or therapeutics. Rather, we have come to realize
      that a large number of our hypertensive patients remain inadequately treated or,
      even more commonly, are receiving no treatment at all. Outcomes research into
      strategies for enhancing patient compliance with treatment and research dealing
      with other issues associated with clinical effectiveness are emerging as leading
      priorities.

PMID- 8565011
TI  - Ambulatory blood pressure monitoring in the diagnosis of hypertension.
AB  - Noninvasive ambulatory blood pressure monitoring is a tool that may be useful for
      selected patients. Interest in the technology has increased because of errors and
      variability in clinic measurements and because of white-coat hypertension. White
      coat hypertension is not benign and is associated with increased left ventricular
      mass and altered lipid and endocrine profiles. Ambulatory blood pressure may be
      useful in white-coat, borderline, and drug-resistant hypertension. Patient hook
      up requires a skilled technician to adjust and calibrate the equipment and
      instruct the patient. Blood pressure and heart rate data should be analyzed with
      respect to diary entries. Observations of the diurnal curve, 24-hour, daytime,
      and nighttime mean blood pressure and blood pressure load are the key items in
      report interpretation. A 24-hour blood pressure mean of at least 134-139/84-87 mm
      Hg is probably indicative of hypertension. A blood pressure load of greater than
      40% predicts target-organ damage. A reduced nocturnal decline is seen in many
      diseases but more importantly is associated with more target organ damage. The
      equipment used for ambulatory monitoring should be independently validated
      against the most recent AAMI or British Hypertension Society protocols. The
      performance of these devices is acceptable at rest but poor with activity. Group
      test-retest performance is excellent, but there is much more variability in
      individual patients. The variability in individuals is probably due to
      differences in activity and behavior. This has implications in the interpretation
      of ambulatory blood pressure parameters. Complications are most often related to
      excess repetitive inflations. Ambulatory blood pressure monitoring affects sleep
      mildly. Ongoing studies will define the place of ambulatory blood pressure
      monitoring in the care of patients.

PMID- 8565012
TI  - Hemodynamic variability and myocardial ischemia.
AB  - A clear understanding of the hemodynamic changes involved in the pathophysiologic
      process responsible for the genesis of myocardial ischemia is essential for the
      selection of the most appropriate anti-ischemic therapy. Based on the predominant
      mechanism responsible for myocardial ischemia, the therapeutic choice can vary
      widely.

PMID- 8565013
TI  - The concept of vascular overload in hypertension.
AB  - In order to determine more accurately hypertensive cardiovascular risk, the term
      vascular overload has been proposed as an alternative to the conventional use of
      diastolic or systolic pressure. This term encompasses both static and pulsatile
      forces opposing flow, that is, arteriolar resistance, large-artery stiffness, and
      early wave reflection. This article explores the diagnostic and therapeutic
      usefulness of the vascular overload concept, especially as it pertains to
      geriatric hypertension.

PMID- 8565014
TI  - A new diagnostic classification for hypertension.
AB  - Many epidemiologic studies have shown that the risks associated with high blood
      pressure are considerably greater in those with target-organ damage and other
      risk factors. Clinical trials also have shown that although lowering blood
      pressure decreases the incidence of premature cardiovascular diseases, those with
      target-organ damage and other cardiovascular risk factors benefit considerably
      more than those with comparable levels of blood pressure who are free of
      complications or additional risk factors. The classification schemes currently in
      use for hypertension, which are based only on the level of blood pressure,
      provide inadequate risk stratification, can be misleading, and may lead to making
      erroneous therapeutic decisions. We propose a new diagnostic classification for
      hypertension that combines the level of blood pressure with the presence of other
      risk factors for premature cardiovascular events and target-organ damage in order
      to provide a more accurate risk assessment and offer superior guidance for
      therapeutic decisions. This scheme includes a new category for the elderly with
      elevated systolic blood pressure, who we now know have excessive morbidity and
      mortality rates if their diastolic blood pressure is low. Our new classification
      scheme is simple to use and yet comprehensive, and we feel it provides better
      risk stratification and is a better guide to therapeutic decision-making than
      those now in use.

PMID- 8565015
TI  - Quantifying cardiovascular risk in hypertension.
AB  - The facts are that blood pressure is a risk factor for cardiovascular disease and
      that its reduction saves lives. This has been convincingly demonstrated. The
      question now is how best to translate that knowledge into practice. Clearly,
      displacement of the whole community's pressure distribution downward would be of
      tremendous benefit. A change of only a few mm Hg, if feasible and without cost in
      health-care terms, would produce more disease prevention than any conceivable
      clinical strategy. Regrettably, the means to achieve this goal are not available.
      New tools to improve dietary and behavioral approaches to attaining these goals
      are desperately needed. For physicians, the immediate issue is how to apply the
      powerful and varied tools that dramatically lower blood pressure in individual
      patients. In this clinical setting, blood pressure must be seen for what it is--a
      reflection of relative risk, a risk factor, and only one of the multiple factors
      that together determine absolute risk. Blood pressure reduction is not curative
      (because high blood pressure is not a disease) but rather is a technique to
      reduce the odds of heart attack, stroke, and renal failure. Hypotensive therapy
      should therefore be applied when the absolute likelihood for a stroke or heart
      attack, is great enough to suggest a real chance for benefit by virtue of the
      reduction of any particular blood pressure level. Therapeutic decisions should
      weigh the potential for benefit as well as the burden of intervention. The worthy
      clinician must define those parameters, assist the patient to assess their
      implications, and finally implement the therapeutic choice that follows, to
      provide the best possible care.

PMID- 8565016
TI  - Metabolic abnormalities in cardiac ischemia.
AB  - Epidemiologic studies have shown a variety of metabolic abnormalities to be risk
      factors for coronary heart disease. Many of these metabolic risk factors coexist
      and may have as a common denominator the presence of insulin resistance and
      hyperinsulinemia. Indeed, clinical studies have demonstrated relationships among
      blood pressure levels, plasma insulin, fibrinogen, plasminogen activator
      inhibitor, factor VIII, triglycerides, and total cholesterol levels and other
      metabolic risk factors. Individuals with hyperinsulinemia generally have low
      levels of high-density lipoprotein, plasminogen activators, and endothelial
      relaxing factors as well. New pharmacologic and hygienic treatment strategies
      that enhance insulin sensitivity and help correct lipoprotein metabolism and
      other metabolic abnormalities will be critical in maximizing coronary risk
      reduction in persons with hypertension, diabetes mellitus, or a family history of
      premature coronary heart disease.

PMID- 8565017
TI  - Metabolic and cardiovascular characteristics of hypertension. Familial aspects.
AB  - There are many convincing data showing that hypertension is an inherited syndrome
      of cardiovascular risk factors that clinically manifest at different times and
      occur independently of one another. These risk factors independently increase the
      potential for a patient to develop coronary heart disease, but when occurring
      together they appear to be synergistic in their ability to cause heart disease.
      It appears that in many patients high blood pressure may be a late manifestation
      of the disease process and may be indicative of a fairly advanced stage of
      disease. Moreover, it is possible that patients with the hypertension syndrome
      will develop coronary artery disease prior to the development of high blood
      pressure. We have recently demonstrated that when comparing cardiovascular risk
      factors in normotensive patients with a family history of hypertension to
      hypertensive patients with and without a family history of hypertension, there
      were no differences among the groups (Fig. 5). All three groups, however, were
      significantly worse off than normotensive subjects without a family history of
      hypertension. Thus, in terms of cardiovascular risk, these "normotensive
      hypertensive" patients were at a risk of developing heart disease equal to that
      of the hypertensive patients, the only difference being that there were not as
      many of such patients. The existence of the hypertension syndrome has some
      important diagnostic and therapeutic consequences. Because of our dependence on
      high blood pressure to isolate patients with the hypertension syndrome, it is
      unlikely that these patients will be treated. With an increased awareness of the
      presence of the hypertension syndrome and better screening techniques, it is
      likely that in the future we will be diagnosing and treating normotensive
      hypertension. We have demonstrated that when comparing normotensive hypertensive
      patients with truly hypertensive patients there are no differences in
      cardiovascular risk factors. The only difference between the groups is that the
      normotensive hypertensive patients do not have the high numbers (which may not be
      particularly important). It is thus likely that normotensive hypertensive
      patients have a risk of developing heart disease similar to that of truly
      hypertensive patients. For this reason, it is possible that normotensive patients
      with the hypertension syndrome will benefit from either conservative or
      pharmacologic therapy that reverses underlying cardiovascular risk factors
      without lowering the blood pressure. In treating high blood pressure in patients
      with the hypertension syndrome, it becomes important to select drugs that will
      reduce blood pressure while having a beneficial or at least a neutral effect on
      all of the other risk factors. Although the reduction in strokes and overall
      mortality in treated hypertensive patients warrants our continued enthusiasm for
      treating high blood pressure, an improved performance in reducing other
      cardiovascular risk factors adds to the benefits of antihypertensive therapy.
      Perhaps treating this disease as a syndrome rather than a number will result in a
      reduction in the incidence of coronary heart disease, as has been seen in the
      incidence of stroke.

PMID- 8565018
TI  - Hypertension and left-ventricular hypertrophy.
AB  - Left-ventricular hypertrophy (LVH), the primary cardiac manifestation of
      hypertension, has been identified as the most powerful risk factor for future
      cardiovascular events causing morbidity and mortality, such as myocardial
      infarction, congestive heart failure, sudden death, and so forth. The increase in
      myocardial mass lowers coronary reserve and enhances cardiac oxygen requirements,
      gives rise to ventricular ectopy, and impairs left-ventricular filling and
      contractility. Besides hypertension, other risk factors such as obesity, advanced
      age, valvular heart disease, and other pathologic disorders can cause an increase
      in the hemodynamic burden and lead to LVH. Nonhemodynamic determinants of left
      ventricular mass include dietary salt intake, alcohol, and neurohormones. LVH and
      its sequelae can be reduced by specific antihypertensive therapy, but despite
      these promising findings, future epidemiologic studies are necessary to document
      the clinical benefits of a reduction in LVH.

PMID- 8565019
TI  - Left-ventricular diastolic function and hypertension.
AB  - Left-ventricular diastolic function is influenced by multiple factors in
      hypertension. These factors include age, left-ventricular hypertrophy, afterload,
      left-atrial pressure, blood pressure, and myocardial stiffness. The influences of
      and interactions among these factors change the filling characteristics of the
      left ventricle and characterize diastolic function. Despite the complex nature of
      these interactions, important clinical information can be noninvasively derived
      by Doppler echocardiography and nuclear scintigraphy. The entire spectrum of
      hypertension is involved with and may alter left-ventricular diastolic function.

PMID- 8565020
TI  - Ambulatory blood pressure monitoring in the evaluation of hypertension therapy.
AB  - During the past decade, ambulatory monitoring of the blood pressure has become an
      important tool for evaluating the pharmacodynamics and clinical efficacy of
      antihypertensive drugs during development. Furthermore, this methodology aids
      physicians in practice in the assessment of blood pressure control in many
      subsets of patients with hypertension.

PMID- 8565021
TI  - Immediate management of severe hypertension.
AB  - A patient with a hypertensive crisis should be ideally treated in an intensive
      care unit. The choice of oral versus parenteral drug depends on the urgency of
      the situation, as well as the patient's general condition. The level to which the
      blood pressure should be lowered varies with the type of hypertensive crisis and
      should be individualized. The choice of parenteral drug is dictated by the
      clinical manifestations and concomitant medical problems associated with the
      hypertensive crisis. There is no predetermined level for the goal of therapy.
      Complications of therapy, mainly hypotension and ischemic brain damage, can occur
      in patients given multiple potent antihypertensive drugs in large doses without
      adequate monitoring. Such complications can be minimized by gentle lowering of
      blood pressure, careful surveillance, and individualization of therapy. A
      relatively asympatomatic patient who presents with severe hypertension, that is,
      a diastolic blood pressure 130 to 140 mm Hg, need not be treated with parenteral
      drugs. These patients should be managed on an individual basis, and the usual
      course would be to intensify or alter the previous antihypertensive therapy.
      Often, asymptomatic patients or those without an acute problem are unnecessarily
      subjected to immediate therapy. Acute alteration of the height of the mercury
      column does little good and may cause harm. A significant immediate change in the
      patient's blood pressure may be self-gratifying to the physician but is not
      indicated for most patients with asymptomatic severe hypertension. Indiscriminate
      use of therapeutic options such as nifedipine and furosemide should be
      discouraged strongly. Once the patient's condition is stable, one should evaluate
      the patient for possible factors that may have contributed to the dangerous
      elevation of blood pressure, such as nonadherence to prescribed therapy or the
      presence or progression of a secondary form of hypertension such as a renal
      artery stenosis. It is crucial to recognize not only what is a hypertensive
      crisis but also what is not an emergency.

PMID- 8565022
TI  - Modern approaches to initiating antihypertensive therapy.
AB  - From the five broad classes of antihypertensive drugs that have been in use long
      enough for adequate clinical experience to be obtained, the most recent report of
      the Joint National Committee on Hypertension recommends drugs from two older
      classes--the diuretics and the beta-adrenergic blockers--as first-line treatment.
      This article argues that newer drugs and in particular the angiotensin-converting
      enzyme inhibitors may be equally or more appropriate as first choice. Physicians
      should choose on the basis of a drug's pharmacologic properties and the patient's
      clinical profile, rather than according to a generic set of rules. Considering
      that the goals of modern antihypertensive therapy are not only lowering of blood
      pressure to prevent complications, but also long-term cardioprotection without
      adverse effects on the quality of life, some newer drugs might even prove more
      cost-effective in the long run.

PMID- 8565023
TI  - Safety profile of over-the-counter naproxen sodium.
AB  - The safety of naproxen sodium for over-the-counter use was evaluated based on 48
      randomized, double-blind, placebo-controlled clinical trials that evaluated
      naproxen/naproxen sodium (NAP) for indications appropriate to, and under,
      conditions common to, nonprescription analgesics. Of the 48 studies, 27 were
      single-dose studies and 21 were multiple-dose studies of 1 to 10 days' duration;
      19 studies included ibuprofen and 9 included acetaminophen. A total of 4138
      patients received naproxen or naproxen sodium (3589 patients received naproxen
      187.5 to 400 mg and 549 received naproxen sodium 220 to 440 mg), 2423 received
      placebo, 1574 received ibuprofen (200 or 400 mg), and 671 received acetaminophen
      (500 to 1000 mg). Adverse-event rates were examined in three sets of comparisons:
      NAP versus placebo (48 studies); NAP versus ibuprofen and placebo (19 studies);
      and NAP versus acetaminophen and placebo (9 studies). Across all 48 studies, 83%
      of both the NAP- and placebo-treated patients reported no adverse events. The
      incidence rates were similar between NAP and placebo, with headache (4.8% NAP,
      6.4% placebo), nausea (3.4% NAP, 3.1% placebo), and somnolence (2.7% NAP, 1.9%
      placebo) the most commonly reported events. Rates of adverse events with NAP,
      ibuprofen, and acetaminophen were similar.

PMID- 8565024
TI  - Double-blind, placebo-controlled comparison of the safety and efficacy of orally
      administered etodolac and nabumetone in patients with active osteoarthritis of
      the knee.
AB  - This 4-week, randomized, double-blind, double-dummy, placebo-controlled, parallel
      group, multicenter study was designed to compare the efficacy and safety of
      etodolac and nabumetone in the treatment of patients with active osteoarthritis
      (OA) of the knee. Ninety-one patients received etodolac 400 mg twice daily, 89
      received nabumetone 1500 mg once daily, and 90 received placebo. Both active
      treatments significantly improved the patients' condition relative to baseline (P
      < or = 0.001) at all evaluations during treatment and relative to placebo (P < or
      = 0.05) by visit 4. Improvement relative to placebo in investigator's global
      assessments was earlier in the etodolac group (ie, by visit 3) than in the
      nabumetone group. At visit 4, improvement in investigator's and patient's global
      assessment scores, and in the distribution of investigator's assessment scores,
      was significantly (P < or = 0.05) greater in the etodolac group than in the
      nabumetone group. Other than hypokalemia, which occurred only in three patients
      in the nabumetone group (P = 0.035), there were no significant differences among
      the groups in the frequency of study events or premature discontinuation from the
      study as a result of study events. Study events considered at least possibly
      treatment related were reported for 26 patients in the etodolac group (28.6%), 20
      in the nabumetone group (22.5%), and 23 in the placebo group (25.6%). The most
      frequently reported symptoms for all groups were dyspepsia, nausea, and headache.
      Four patients treated with nabumetone (4.5%) had elevations in aspartate
      aminotransferase or alanine aminotransferase during treatment. The results of
      this study show that etodolac 400 mg twice daily is at least as effective as
      nabumetone 1500 mg once daily and is equally well tolerated in the treatment of
      patients with active OA of the knee; etodolac may have an earlier onset of action
      and/or a relatively greater efficacy in patient and investigator global
      assessments than nabumetone.

PMID- 8565025
TI  - A double-blind, multicenter comparative study of two regimens of clindamycin
      hydrochloride in the treatment of patients with acute streptococcal
      tonsillitis/pharyngitis.
AB  - In a double-blind, prospective, randomized, multicenter study, 164 patients with
      a clinical and bacteriologic diagnosis of acute streptococcal
      tonsillitis/pharyngitis were enrolled to compare the efficacy and safety of two
      regimens of clindamycin. A rapid identification test of Group A beta-hemolytic
      streptococci (GABHS) was used to initiate the therapy; however, a positive
      tonsillar/pharyngeal culture was required at pretreatment to determine if the
      patient was assessable. Another culture was repeated at least 2 days after the 10
      days of drug therapy. From 164 patients enrolled (mean age, 27.7 years; range, 14
      to 60 years), 141 were assessable for efficacy; 22 patients were excluded because
      they did not have a positive culture at pretreatment and 1 patient did not
      complete the study due to a side effect (rash). All patients were included in the
      safety analysis. Patients received either clindamycin hydrochloride capsules 150
      mg four times per day (QID) or clindamycin hydrochloride capsules 300 mg two
      times per day (BID) and placebo capsules BID for 10 days. There were no
      significant differences between groups in terms of demographics, medical history,
      and evolution of symptoms. The clinical efficacy rate in the two groups at day 12
      was as follows: QID group--cured, 64 (92.8%) of 69 patients; improved, 5 (7.2%)
      of 69 patients; BID group--cured, 67 (93.1%) of 72 patients; improved, 5 (6.9%)
      of 72 patients. There were no significant differences between the groups. Both
      regimens were well tolerated with only 1 patient in the QID group who did not
      complete the therapy due to a rash.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8565026
TI  - Hydroxychloroquine treatment of patients with human immunodeficiency virus type
      1.
AB  - Hydroxychloroquine (HCQ), an antimalarial agent used to treat patients with
      autoimmune diseases, has been shown to suppress human immunodeficiency virus type
      1 (HIV-1) replication in vitro in T cells and monocytes by inhibiting
      posttranscriptional modification of the virus. These in vitro observations have
      been expanded into an in vivo study of HCQ as a potential anti-HIV-1 agent in HIV
      1-infected patients. A randomized, double-blind, placebo-controlled clinical
      trial was conducted in 40 asymptomatic HIV-1-infected patients who had CD4+
      counts between 200 and 500 cells/mm3. Patients were randomly assigned to receive
      either HCQ 800 mg/d or placebo for 8 weeks. Virologic and immunologic parameters,
      including HIV-1 ribonucleic acid (RNA) via use of polymerase chain reaction,
      viral culture, antigen and mitogen responses, and proinflammatory cytokine levels
      were measured at the beginning and end of the study. The amount of recoverable
      HIV-1 RNA in plasma declined significantly in the HCQ group over the 8-week
      period (P = 0.022), while it increased in the placebo group. The percentage of
      CD4+ T cells remained stable in the HCQ-treated group (18.1 +/- 9.2% before
      treatment vs 18.6 +/- 10.5% after treatment) and fell significantly in the
      placebo group (21 +/- 7% before treatment vs 19.3 +/- 6.3% after treatment; P =
      0.032). However, this was not reflected as a change in absolute CD4+ counts for
      either group (HCQ, 262.8 +/- 166 cells/mm3 vs 251 +/- 163 cells/mm3; placebo, 312
      +/- 121 cells/mm3 vs 321 +/- 124 cells/mm3). Mitogen- and antigen-specific
      responses remained constant in the HCQ group while T cell proliferative responses
      to Candida decreased in the placebo group (4.8 +/- 3.6 x 10(3) SI [stimulation
      index] vs 3.0 +/- 3.0 x 10(3) SI; P = 0.032). Lastly, serum interleukin 6 levels
      declined in the HCQ group (14.3 +/- 13.5 U/mL vs 12.0 +/- 16.7 U/mL; P = 0.023)
      but not in the placebo group (11.3 +/- 8.8 U/mL vs 7.0 +/- 11.7 U/mL); this was
      coincident with a decrease in serum immunoglobulin (Ig)G (2563 +/- 1352 mg/mL vs
      2307 +/- 1372 mg/dL; P = 0.032), compared with the placebo group (2733 +/- 1473
      mg/dL vs 2709 +/- 1501 mg/dL). No other parameters, including serum p24 and beta
      2 microglobulin levels, were altered by HCQ therapy. HCQ thus may be useful in
      the treatment of patients with HIV-1 infection.

PMID- 8565027
TI  - Lack of hypothalamic-pituitary-adrenal axis suppression with once-daily or twice
      daily beclomethasone dipropionate aqueous nasal spray administered to patients
      with allergic rhinitis.
AB  - The potential for a newly developed, double-strength (0.084%) beclomethasone
      dipropionate (BDP) aqueous (AQ) nasal suspension to produce effects associated
      with exposure to systemic corticosteroids was assessed by the plasma cortisol
      response to cosyntropin stimulation induced by a 6-hour intravenous infusion of
      250 micrograms of cosyntropin in 500 mL of normal saline. Sixty-four patients
      with allergic rhinitis were enrolled in this study. Patients were randomly
      assigned to one of the following four treatment groups: (1) BDP AQ Forte (0.084%)
      nasal spray 336 micrograms once daily; (2) BDP AQ (0.042%) nasal spray 168
      micrograms twice daily; (3) placebo nasal spray twice daily; or (4) oral
      prednisone 10 mg once daily in the morning. After 36 consecutive days of
      treatment, there was a significant (P < 0.01) difference in the plasma cortisol
      response to cosyntropin stimulation between the prednisone and placebo groups;
      however, there were no significant differences between the BDP AQ Forte or the
      BDP AQ groups compared with the placebo group. Secondary analyses comparing BDP
      AQ Forte administered as 336 micrograms once daily with BDP AQ administered as
      168 micrograms twice daily showed no significant differences in plasma cortisol
      responses to cosyntropin stimulation. No serious adverse events were reported.
      Adverse events consisted of headache, pharyngitis, or nasal irritation, with
      headache being reported most frequently. These adverse events were similarly
      distributed among active treatment groups and were similar to placebo. No
      clinically relevant changes were observed in any treatment group in findings on
      clinical laboratory tests, physical examination, or electrocardiography. Vital
      signs, obtained daily, were consistent with values observed in healthy
      individuals. No patient exhibited signs of oral candidiasis. All patients met the
      plasma cortisol concentration criteria for discharge relative to expected
      hypothalamic-pituitary-adrenal axis function. In conclusion, there were no
      significant differences in plasma cortisol responses to cosyntropin stimulation
      between groups of patients with allergic rhinitis treated with either BDP AQ
      Forte (0.084%) nasal spray 336 micrograms once daily or BDP AQ (0.042%) nasal
      spray 168 micrograms twice daily compared with the placebo group. These results
      indicate that the dosing regimens of BDP AQ nasal suspensions used in this study
      lack systemic effects and are safe and well tolerated.

PMID- 8565028
TI  - Isradipine versus captopril in patients with essential hypertension.
AB  - We conducted a double-blind, crossover study comparing the antihypertensive
      effects of isradipine versus captopril in patients with essential hypertension.
      Seventeen patients (8 men, 9 women; 6 whites, 11 blacks) completed both phases of
      the study, which consisted of two 5-week treatment periods separated by 2 weeks
      of placebo treatment. Each drug was randomly allocated to half the patients as
      the first drug and half as the second drug they received. Ambulatory blood
      pressure (BP) monitoring was carried out on the day before treatment and the last
      day of each active treatment. Both drugs were effective and well tolerated but
      isradipine was more effective overall than captopril in lowering BP (9.4% vs
      3.9%, respectively; P < 0.02). Black patients had significantly higher BP at
      baseline than white patients; furthermore, black patients responded better to
      isradipine than to captopril. White patients had a smaller decrease in blood
      pressure with both drugs than did black patients, but white patients still
      attained a lower diastolic BP with captopril than did black patients (88 +/- 2 mm
      Hg vs 96 +/- 9 mm Hg; P < 0.01). There was no correlation between the
      pretreatment plasma levels of pressor hormones (plasma renin activity,
      catecholamines, and arginine vasopressin) and the magnitude of BP response to
      either drug, but the decrease in BP in response to captopril correlated
      significantly with the increase in plasma renin activity during treatment (r = 
      .84; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8565029
TI  - Efficacy and safety of etodolac and naproxen in patients with osteoarthritis of
      the knee: a double-blind, placebo-controlled study.
AB  - A multicenter, parallel-group, double-blind, randomized, outpatient study
      compared the efficacy and safety of etodolac versus naproxen in patients with
      osteoarthritis of the knee. After a washout period free of nonsteroidal anti
      inflammatory drugs, 254 patients self-administered etodolac 400 mg (n = 86),
      naproxen 500 mg (n = 82), or placebo (n = 86) twice daily for 4 weeks. Compliance
      exceeded 90% in all three groups. Primary efficacy variables improved
      progressively from baseline in all three groups. The extent of improvement was
      greater in the etodolac and naproxen groups than in the placebo group (P < or =
      0.003), except with respect to target joint tenderness (P = 0.028, etodolac vs
      placebo; P = 0.013, naproxen vs placebo). There were no statistical differences
      between active treatment groups (P > 0.1). At end point, twice as many patients
      responded in the etodolac (59%) and naproxen groups (51%) than in the placebo
      group (26%; P < or = 0.01). There were no significant between-group differences
      in the numbers of patients who had an adverse experience, a serious adverse
      experience, or an adverse experience leading to study discontinuation; there were
      also no significant between-group differences in the distribution of adverse
      experiences. There were no unexpected clinical or laboratory experiences.
      Etodolac 400 mg twice daily was as effective and safe as naproxen 500 mg twice
      daily and both were superior to placebo in the management of osteoarthritis of
      the knee.

PMID- 8565030
TI  - Efficacy of long-term treatment with nipradilol, a nitroester-containing beta
      blocker, in patients with mild-to-moderate essential hypertension.
AB  - The effects of long-term treatment with nipradilol, a nitroester-containing beta
      blocker, on casual and 24-hour blood pressures were studied in 70 patients with
      mild-to-moderate essential hypertension. Antihypertensive effects of nipradilol
      on casual blood pressure were observed in 68% of patients. Nipradilol reduced
      pulse rates, but no bradycardia was observed. The usefulness of nipradilol in the
      present study was 65%. The results of ambulatory blood pressure monitoring
      indicated that nipradilol reduced systolic blood pressure more than diastolic
      blood pressure, and reduced blood pressure during waking more than during sleep.
      These results suggest that nipradilol is a safe and useful long-term
      antihypertensive drug in both young and older patients with mild-to-moderate
      essential hypertension. When administered twice daily, nipradilol is effective
      throughout a 24-hour period.

PMID- 8565031
TI  - Patient responsiveness to calcitonin salmon nasal spray: a subanalysis of a 2
      year study.
AB  - A subanalysis of results from a randomized, double-blind, placebo-controlled,
      parallel-group, 2-year study was conducted to evaluate the response of individual
      patients to therapy with 200 IU/d calcitonin salmon nasal spray compared with
      placebo in postmenopausal women who had low bone mass. All patients received 500
      mg/d of oral supplemental calcium. A response to therapy was defined as an
      increase from baseline in lumbar vertebral bone mineral density, measured by use
      of dual-energy x-ray absorptiometry, at the end of 2 years of treatment. Of 41
      valid completers (ie, patients who met the entry criteria, were compliant with
      the protocol, and completed the study) treated with calcitonin salmon nasal
      spray, 31 (76%) responded positively to treatment. Of 40 valid completers who
      received placebo, 25 (63%) lost bone mass (P = 0.001 between groups). The
      relative risk of bone loss for patients receiving calcitonin salmon nasal spray
      was 0.19 (95% confidence interval, 0.07 to 0.50), representing an 81% risk
      reduction. This subanalysis demonstrates that the benefits of calcitonin salmon
      nasal spray therapy were seen in the majority of women studied. Calcitonin salmon
      nasal spray represents an effective therapeutic alternative for osteoporotic
      women more than 5 years postmenopause who reject or cannot tolerate estrogens or
      for whom estrogens are contraindicated.

PMID- 8565032
TI  - Comparison of the efficacy and safety of nifedipine coat-core versus amlodipine
      in the treatment of patients with mild-to-moderate essential hypertension.
      Hypertension Study Group.
AB  - The antihypertensive efficacy and safety of once-daily nifedipine coat-core was
      compared with that of once-daily amlodipine in a multicenter, prospective, double
      blind, randomized, parallel-group study in which titration was based on response.
      The study consisted of a 2-week, single-blind, placebo run-in period followed by
      an 8-week double-blind treatment period. Double-blind treatment began with
      nifedipine coat-core 30 mg or amlodipine 5 mg. After 4 weeks of double-blind
      therapy, patients with a trough seated diastolic blood pressure (DBP) > or = 90
      mm Hg received an increased dose of nifedipine coat-core (60 mg) or amlodipine
      (10 mg). A total of 207 patients received the study medication at 12 private
      practice medical centers. Ambulatory blood pressure monitoring (ABPM) was
      performed at six medical centers with 38 nifedipine coat-core and 37 amlodipine
      patients. Data from 176 patients were valid for the primary efficacy analysis.
      Treatment groups were well matched with respect to baseline demographic and
      disease characteristics. During the study period, 59 (65.6%) nifedipine coat-core
      patients remained on their original 30-mg dose of study medication compared with
      52 (60.5%) amlodipine patients who remained on the 5-mg starting dose. Mean
      trough blood pressure at baseline was 160.9/101.9 mm Hg in the nifedipine coat
      core patients compared with 160.5/101.8 mm Hg in the amlodipine patients. Mean
      trough blood pressures at end point were 141.3/85.5 mm Hg and 140.7/85.9 mm Hg in
      the nifedipine coat-core and amlodipine groups, respectively. Equivalence between
      the two treatment groups was demonstrated based on the difference between
      amlodipine and nifedipine coat-core in the change from baseline in trough seated
      DBP (90% confidence interval, -0.50 to 2.59). Systolic blood pressure and 24-hour
      ABPM data supported the equivalent antihypertensive efficacy of the two
      treatments. Both drugs were well tolerated and had similar safety profiles.
      Nineteen patients in the amlodipine group experienced at least one adverse event
      compared with 12 in the nifedipine coat-core group. The amlodipine patients
      tended toward a later occurrence of adverse events plus a greater number of
      events, particularly edema and gastrointestinal symptoms. More patients in the
      nifedipine coat-core group (n = 3) than in the amlodipine group (n = 1)
      discontinued treatment because of adverse events.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8565033
TI  - An open-label, noncomparative study to evaluate the efficacy, safety, and
      tolerability of azithromycin in the treatment of patients with acute sinusitis.
AB  - The efficacy, safety, and tolerability of a 5-day, once-daily course of
      azithromycin were assessed in patients with acute sinusitis. Patients received
      two 250-mg capsules of azithromycin on day 1 and one 250-mg capsule on days 2
      through 5. Of 102 clinically assessable patients, 27 (26.5%) were cured and 69
      (67.6%) were improved on days 5 to 7. At days 12 to 16, 88 (86.3%) had a
      favorable clinical response. A total of 64 patients experienced adverse events;
      in all but two patients, adverse events were of mild or moderate severity. Thus
      azithromycin given once daily for 5 days was an effective treatment for patients
      with acute sinusitis.

PMID- 8565034
TI  - Efficacy and safety of mepyramine-theophylline-acetate in the treatment of
      asthmatic crisis in children.
AB  - Mepyramine-theophylline-acetate (MTA), a theophylline derivative combined with an
      antihistamine, is used to treat patients with asthma. A double-blind, randomized,
      prospective, parallel-group study was conducted to evaluate the efficacy and
      safety of MTA in the treatment of asthmatic crisis in children 2 to 6 years of
      age. Forty patients with mild-to-moderate asthma were admitted to the study. The
      MTA group received 8 mg/kg per day of MTA by mouth in three divided doses for 7
      days. The other group received 50 microL/kg per day of placebo in three divided
      doses for 7 days. Salbutamol (albuterol) syrup was used as the rescue drug if
      manifestations of asthma persisted. Both the MTA group and the placebo group had
      similar demographic characteristics at baseline. Both groups showed improvement
      of the asthma symptoms (cough, dyspnea, hypoventilation, and wheezing), as
      evaluated by the investigators at days 3 and 7. Patient diary scores showed
      earlier improvements in the MTA group than in the placebo group. Both groups
      showed improvement in peak flow at days 3 and 7 (P = 0.005). The control group
      used more doses of salbutamol than the MTA group on days 2 through 6 and globally
      (mean +/- SD, 6.79 +/- 9.11 doses vs 1.29 +/- 2.23 doses). The improvements in
      the placebo group were thought to be due to salbutamol. Three MTA patients
      dropped out of the trial, one because the parents felt that the treatment was not
      effective and two because of gastrointestinal manifestations (epigastric
      discomfort and vomiting). In the placebo group, two patients dropped out. One
      patient had epigastric discomfort and the other had to be treated in the
      emergency department for an exacerbation of the asthma. We conclude that MTA may
      be a good therapeutic option for the treatment of asthmatic crisis in children 2
      to 6 years of age.

PMID- 8565035
TI  - Lipoprotein(a) concentration in patients with chronic active hepatitis C before
      and after interferon treatment.
AB  - Patients with chronic active hepatitis C show low lipoprotein(a) (Lp[a]) values.
      We studied the changes in Lp(a) levels caused by treatment with interferon in 24
      patients (9 men and 15 women; mean age, 56.8 +/- 7.3 years) affected by chronic
      active hepatitis C. Fifteen healthy subjects (6 men and 9 women; mean age, 57.4
      +/- 10.3 years) were used as controls. All of the patients with chronic hepatitis
      C were treated with intramuscular interferon, 3 million units 3 times per week
      for 6 months. These patients had lower baseline serum Lp(a) concentrations than
      the controls (4.8 +/- 3.8 mg/dL vs 13.4 +/- 10.3 mg/dL, respectively; P =
      0.0007). A significant increase in Lp(a) levels (6.6 +/- 7.2 mg/dL; P = 0.05)
      occurred after 6 months of treatment in patients with chronic active hepatitis C.
      Only complete responders presented a significant increase in Lp(a) values (P =
      0.01). We believe that increased Lp(a) levels represent an expression of improved
      liver functions.

PMID- 8565036
TI  - Effects of long-term cilazapril treatment on glucose and lipid metabolism in
      hypertensive patients with non-insulin-dependent diabetes mellitus.
AB  - The effects of long-term cilazapril treatment on glucose and lipid metabolism
      were assessed in 25 hypertensive patients with non-insulin-dependent diabetes
      mellitus (NIDDM). Patients were treated with 0.5 to 1 mg of cilazapril once daily
      or a combination of cilazapril and other antihypertensive drugs once daily for 48
      weeks. Both systolic and diastolic blood pressures were significantly reduced (P
      < 0.001) throughout the study with no significant changes in heart rate and no
      adverse effects such as cough. There were no significant changes in body mass
      index or serum levels of glycated hemoglobin A1c, fructosamine, total
      cholesterol, triglycerides, lipoproteins (high-density lipoprotein cholesterol,
      low-density lipoprotein cholesterol, and very-low-density lipoprotein
      cholesterol), or apolipoproteins (apo A-I, apo C-II, apo C-III, apo B, and apo
      E). Cilazapril caused a significant increase (P < 0.05) in levels of apo A-II and
      a significant decrease (P < 0.05) in the apo B:apo A-I ratio, an index of
      arteriosclerosis. These results suggest that cilazapril has favorable effects on
      glucose and lipid metabolism and that it may be useful as the first or second
      choice of antihypertensive drugs in hypertensive patients with NIDDM.

PMID- 8565037
TI  - Comparison of the efficacy and safety of oxaprozin and nabumetone in the
      treatment of patients with osteoarthritis of the knee.
AB  - This multicenter, 6-week, double-blind, placebo-controlled, parallel-group study
      compared the efficacy and safety of oxaprozin 1200 mg once daily with that of
      nabumetone 1000 mg once daily in patients with moderate-to-severe osteoarthritis
      (OA) of the knee. To be eligible, patients had to experience a flare of OA within
      2 weeks of discontinuing their usual OA medication (nonsteroidal anti
      inflammatory drug or analgesic). Eligible patients were assessed at baseline and
      then randomized to receive oxaprozin (n = 109), nabumetone (n = 110), or placebo
      (n = 109). Efficacy assessments were performed at weeks 1, 2, 4, and 6. Primary
      efficacy variables included knee pain on weight bearing, knee pain on motion, and
      patient's and physician's global assessments of OA. Secondary efficacy variables
      included pain intensity, time to walk 50 feet, and duration of morning stiffness.
      Safety was evaluated by use of routine laboratory analyses; physical examination
      at screening, baseline, and week 6 (or study termination); assessment of symptoms
      at baseline and at each visit; and testing stools for occult blood at screening
      and between week 4 and the final visit. Adverse events were monitored throughout
      the study. Between-group differences in efficacy variables were evident by week
      1. The mean change in improvement from baseline with oxaprozin compared with
      placebo was statistically significant in favor of oxaprozin at weeks 1, 2, 4, and
      6 for all primary efficacy variables. The mean change in improvement from
      baseline with nabumetone compared with placebo, however, was statistically
      significant only at week 1 for knee pain on motion, patient's global assessment,
      and physician's global assessment. The mean change in improvement from baseline
      was statistically significant (P < or = 0.035) in favor of oxaprozin versus
      nabumetone at weeks 2 and 6 for all four primary efficacy variables and also at
      week 4 for knee pain on motion. The incidence of adverse clinical events between
      treatment groups was not statistically significant. However, nine oxaprozin
      treated patients had asymptomatic liver enzyme elevations reported as adverse
      events. Four of these patients had reversible elevations of aspartate
      aminotransferase and alanine aminotransferase greater than three times the upper
      limit of normal range (P < 0.05); two of these patients were taking other
      medications known to induce liver enzyme abnormalities. The study showed that
      oxaprozin 1200 mg once daily was statistically significantly more efficacious
      than nabumetone 1000 mg once daily for the treatment of patients with moderate-to
      severe OA of the knee. Both drugs were clinically well tolerated.

PMID- 8565038
TI  - Two approaches to comparing hospital charges between cadaveric renal transplant
      patients who received orthoclone OKT 3 sterile solution or Atgam sterile solution
      for induction therapy.
AB  - The objectives of this study were: (1) to compare total hospital charges for a
      sample of cadaveric renal transplant patients categorized according to the type
      of induction therapy used (Orthoclone OKT3 Sterile Solution or Atgam Sterile
      Solution); (2) to compare specific charge categories between the two groups; and
      (3) to examine the relationship between charges and a set of independent
      variables. A retrospective review was conducted of hospital charges associated
      with a sample of renal transplant patients. The overall sample for this study
      comprised 510 patient discharges from 22 hospitals in the United States.
      Comparisons between the OKT3 and Atgam groups were made for total and specific
      charge categories using two different approaches to help control variations in
      charges that were not related to the type of induction therapy used. The first
      approach consisted of t test or chi-square comparisons between the groups for
      subsets of observations that had been identified in a stepwise fashion. These
      judgment samples were defined to remove sources of variation in charges other
      than those resulting from the type of induction therapy selected. The second
      approach used multiple linear regression analysis to help statistically control
      variation in charges from other sources. The results showed that higher drug
      charges in the Atgam group were offset by lower charges in other categories (P <
      0.05). These findings suggest that hospital formulary committees should consider
      all relevant costs, not just drug acquisition costs, when selecting products.
      However, further investigation is warranted to explore differences in charges due
      to: (1) between-hospital variation; (2) patients' severity of illness before
      receiving induction therapy; and (3) differences in side-effect profiles for the
      two induction therapies.

PMID- 8565039
TI  - Cost analysis of propofol versus thiopental induction anesthesia in outpatient
      laparoscopic gynecologic surgery.
AB  - This study investigated the cost of propofol versus thiopental anesthesia in 243
      patients who underwent outpatient laparoscopic gynecologic surgery. Patients
      records were analyzed for medication use, duration of surgery, anesthesia,
      recovery room stay, and associated costs. Despite the higher drug cost for
      propofol, the total mean cost was $273.00 less per patient for patients receiving
      propofol induction anesthesia. Extension of these data translates into cost
      savings of approximately $7900.00 if propofol had been used for all patients.
      Although the duration of surgery for the propofol group was shorter by nearly 12
      minutes, the anesthesia duration and recovery room stay were both longer for the
      thiopental group, reflecting the longer duration of action of thiopental.
      Although the realized cost savings of drugs, surgery, anesthesia, and recovery
      time when propofol versus thiopental is used for outpatient laparoscopic
      gynecologic surgery are relatively small on an individual patient basis, cost
      savings may become more significant if larger patient populations are studied.

PMID- 8565040
TI  - Translation and validation of the American Urological Association symptom index
      into Spanish.
AB  - The US population is multiethnic in composition: many languages thrive, and
      Spanish is the second most frequently spoken language. The Hispanic population is
      one of the fastest growing ethnic groups in the United States. The majority of
      Hispanics speak Spanish at home (63%), and a significant proportion speak little
      or no English (25%). The purpose of this study was to translate the American
      Urological Association (AUA) symptom index into Spanish and to validate the final
      translation. To translate the AUA symptom index, a combination of four methods
      was used: forward- and back-translation, evaluation of the translated version by
      a committee, testing of the translated index with healthy bilingual subjects, and
      correlation of the scores of bilingual patients with benign prostatic hyperplasia
      (BPH) who were administered both the AUA symptom index and the Maine Medical
      Assessment Program (MMAP) symptom index. One-way analysis of variance was used to
      compare the scores of healthy bilinguals, and no significant differences were
      found between the English and Spanish versions. Multivariate analysis of variance
      revealed that none of the seven questions showed statistical differences between
      the Spanish and English versions. This provided further evidence that the
      questions were translated properly into Spanish and that they can be used to
      measure the same concepts as the English questions. After both indexes (AUA and
      MMAP) were administered to bilingual patients with BPH, the study found that the
      correlation between the Spanish version of the AUA symptom index and the MMAP was
      0.85. This is further evidence that the Spanish version of the AUA symptom index
      is accurate and can be used to measure the symptoms of BPH as well as the English
      counterpart.

PMID- 8565041
TI  - Drug utilization review of concomitant use of specific serotonin reuptake
      inhibitors or clomipramine with antianxiety/sleep medications.
AB  - Side effects of some antidepressants include anxiety and insomnia. A
      retrospective drug utilization review was conducted to determine the amount of
      concurrent use of an antidepressant with medication that may counteract these
      side effects. Texas Medicaid claims data for 1993 included more than 30,000
      patients receiving a specific serotonin reuptake inhibitor (SSRI) or
      clomipramine. A total of 35.0% of these patients were also taking a medication
      that could be used to relieve anxiety or induce sleep, and 15.2% of the total
      were receiving once-daily dosing of the latter type of medication. Concomitant
      use of SSRIs or clomipramine with trazodone occurred in 7.7% of the patients.

PMID- 8565042
TI  - The pharmaceutical industry in Cuba.
AB  - Cuba has developed a relatively sophisticated pharmaceutical sector, originally
      to provide medicinal products for her own population and, more recently, to earn
      hard currency through exports. Cuba has achieved both of these goals despite the
      US trade embargo, which isolates Cuba from commercial relations with US firms.
      Cuba is opening its economy to firms from other countries through the use of
      joint ventures and other forms of cooperation. US firms are unable to avail
      themselves of these opportunities, and the opportunities are thus being lost. In
      the case of pharmaceuticals, the Cubans recognize that they need assistance,
      particularly in the areas of marketing and packaging. Allowing the participation
      of US firms in the Cuban pharmaceutical industry could enhance the possibility of
      improving worldwide health care.

PMID- 8565043
TI  - Specific delta-opioid antagonists exert an agonist-independent inhibitory effect,
      similar to the agonist, on the release of GnRH in vitro.
AB  - 1. In in vitro studies with adult male rats we have recently shown that the delta
      opioid agonist DTLET inhibits the release of the Gonadotropin-Releasing Hormone
      (GnRH) from hypothalamic fragments containing the arcuate nucleus and the median
      eminence. This effect is receptor mediated and eicosanoid dependent (Gerozissis
      et al., 1993). 2. In the present study we report that the delta-opioid
      antagonists with negative intrinsic activity, Diallyl-G and ICI 174864, applied
      under the same experimental conditions (30 min static incubations at 37 degrees
      C, in a potassium rich milieu), in the absence of the agonist DTLET, also exert a
      similar to the agonist inhibitory effect on the release of GnRH. 3. The dose
      dependent inhibitory effect of Diallyl-G on GnRH release is reversed by
      increasing concentrations of DTLET. The mu and delta opioid antagonist, naloxone
      is without effect in the absence of DTLET. However, naloxone acts as an
      antagonist on the Diallyl-G-induced inhibition of GnRH release. 4. Diallyl-G also
      inhibits the release of prostaglandin E2 (PGE2). In the presence of indomethacin
      or nordihydroguaiaretic acid, Diallyl-G is ineffective to further inhibit the
      release of GnRH. These latter observations taken together with the results of
      eicosanoid estimation suggest that PGE2 but not leukotrienes participate in the
      agonist-independent effects of Diallyl-G on GnRH release. 5. Therefore these
      results support the hypothesis that delta-opioid antagonists with negative
      intrinsic activity exert agonist-independent biological responses similar to
      those of the agonists.

PMID- 8565044
TI  - Parvalbumin-immunoreactive proteins in the nervous system of planarians.
AB  - 1. Using immunological methods, we have identified parvalbumin-like material in
      the triclade flatworms, Polycelis nigra, Polycelis auriculata, Crenobia alpina,
      Dugesia tahitiensis, and Dugesia polychroa. 2. Western immunoblot analysis of
      these five species revealed heat stable parvalbumin-immunoreactive proteins
      between 32 kD and 44 kD. 3. Proteins at 19 and 32 kD revealed intense labeling
      with 45Ca2+. 4. Double immunodiffusion of planarian supernatants showed complete
      fusion of precipitates, indicating immunological relatedness of the parvalbumin
      like material among the species investigated. 5. Immunocytochemical studies
      exhibit parvalbumin-immunoreactive material exclusively in neurons supporting the
      notion of an early evolutionary appearance of these proteins in the nervous
      system.

PMID- 8565045
TI  - Differential desensitization properties of rat neuronal nicotinic acetylcholine
      receptor subunit combinations expressed in Xenopus laevis oocytes.
AB  - 1. Chronic administration of nicotine up-regulates mammalian neuronal nicotinic
      acetylcholine receptors (nAChRs). A key hypothesis that explains up-regulation
      assumes that nicotine induces desensitization of receptor function. This is
      correlated with behaviorally expressed tolerance to the drug. 2. The present
      experiments were conducted to: (a) obtain information on the nicotine-induced
      desensitization of neuronal nAChR function, a less understood phenomenon as
      compared to that of the muscle and electric fish receptor counterparts; (b) test
      the hypothesis that different receptor subunit combinations exhibit distinct
      desensitization patterns. 3. Xenopus laevis oocytes were injected with mRNAs
      encoding rat receptor subunits alpha 2, alpha 3, or alpha 4 in pairwise
      combination with the beta 2 subunit. The responses to various concentrations of
      acetylcholine (ACh) or nicotine were analyzed by the two electrode voltage clamp
      technique. 4. Concentration-effect curves showed that nicotine was more potent
      than ACh for all the receptor subunit combinations tested. Only the alpha 4 beta
      2 combination exhibited a depression of the maximum effect at concentrations
      higher than 20 microM nicotine. 5. After a single nicotine pulse, receptor
      desensitization (calculated as a single exponential decay) was significantly
      slower for alpha 4 beta 2 than for either alpha 3 beta 2 or alpha 2 beta 2. 6.
      Concentrations of nicotine that attained a near maximum effect were applied,
      washed, and re-applied in four minute cycles. The responses were calculated as
      percentages of the current evoked by the initial application. Following 16
      minutes of this protocol, the alpha 4 beta 2 combination showed a greater
      reduction of the original response as compared to the alpha 2 beta 2 and alpha 3
      beta 2 subunit combinations. Taking points 5 and 6 together, these experiments
      suggest that the alpha 4 beta 2 receptor subtype desensitizes at a slower rate
      and remains longer in the desensitized state. 7. Because alpha 4 beta 2 is the
      main receptor subunit combination within the brain and is up-regulated by
      nicotine, our data may be important for understanding the molecular basis of
      tolerance to this drug.

PMID- 8565046
TI  - Mutations in the M1 region of the nicotinic acetylcholine receptor alter the
      sensitivity to inhibition by quinacrine.
AB  - 1. Site directed mutagenesis was used to alter the structure of Torpedo
      californica nicotinic acetylcholine receptor (nAChR) and to identify amino acid
      residues which contribute to noncompetitive inhibition by quinacrine. Mutant
      receptors were expressed in Xenopus laevis oocytes injected with in vitro
      synthesized mRNA and the whole cell currents induced by acetylcholine (ACh) were
      recorded by two electrode voltage clamp. 2. A series of mutations of a highly
      conserved Arg at position 209 of the alpha subunit of Torpedo californica nAChR
      revealed that positively charged amino acids are required for functional receptor
      expression. Mutation of Arg to Lys (alpha R209K) or His (alpha R209H) at position
      209 shifted the EC50 for ACh slightly from 5 microM to 12 microM and increased
      the normalized maximal channel activity 8.5- and 3.2-fold, respectively. 3. These
      mutations altered the sensitivity of nAChR to noncompetitive inhibition by
      quinacrine. The extent of inhibition of ion channel function by quinacrine was
      decreased as pH increased in both wild type and mutant nAChR suggesting that the
      doubly charged form of quinacrine was responsible for the inhibition. 4. Further
      mutations at different positions of the alpha subunit suggest the contribution of
      Pro and Tyr residues at positions 211 and 213 to quinacrine inhibition whereas
      mutations alpha I210A and alpha L212A did not have any effects. None of these
      mutations changed the sensitivity of nAChR to inhibition by a different
      noncompetitive inhibitor, chlorpromazine. 5. These findings support a hypothesis
      that the quinacrine binding site is located in the lumen of the ion channel. In
      addition, the quantitative effect of point mutations at alternate positions on
      the sensitivity of quinacrine inhibition suggests that the secondary structure at
      the beginning of M1 region might be beta sheet structure.

PMID- 8565047
TI  - Effect of external K+, Ca2+, and Ba2+ on membrane potential and ionic conductance
      in rat astrocytes.
AB  - 1. The purpose of this study was (a) to identify if astrocytes show a similar non
      Nernstian depolarization in low K+ or low Ca2+ solutions as previously found in
      human glial and glioma cells, and (b) to analyze the influence of the K+
      conductance on the membrane potential of astrocytes. 2. The membrane potential
      (Em) and the ionic conductance were studied with whole-cell patch-clamp technique
      in neonatal rat astrocytes (5-9 days in culture) and in human glioma cells (U
      251MG). 3. In 3.0 mM K+ Em was -75 +/- 1.0 mV (mean +/- SEM, n = 39) in rat
      astrocytes and -79 +/- 0.7 mV (n = 5) in U-251MG cells. In both cell types Em
      changed linearly to the logarithm of [K+]0 between 3.0 and 160 mM K+ free medium
      caused astrocytes to hyperpolarize to -93 +/- 2.7 mV (n = 21) and U-251MG cells
      to depolarize to -27 +/- 2.1 mV (n = 3). 4. The I-E curve did not show inward
      rectification in astrocytes at this developmental stage. The slope conductance
      (g) exhibited only a small decrease (-19%) in K+ free solution and no significant
      change in 160 mM K+. 5. Ba2+ (1.0 mM) depolarized astrocytes to -45 +/- 2.9 mV (n
      = 11), decreasing the slope conductance (g) by 42.4 +/- 8.3% (n = 11). Ca2+ free
      solution depolarized astrocytes to -53 +/- 3.4 mV (n = 12) and resulted in a
      positive shift of the I-E curve, increasing g by 15.3 +/- 8.2% (n = 8). 6.
      Calculations indicated that a block of K+ channels explains the depolarizing
      effect of Ba2+. The effects of K+ free or Ca2+ free solutions on Em can be
      explained by a transformation of K+ channels to non-specific leakage channels.
      That astrocytes show a different reaction to low K+ than glioma cells can be
      related to the lack of inwardly rectifying K+ channels in astrocytes at this
      developmental stage.

PMID- 8565048
TI  - Relations between development and regeneration of tadpole spinal cord.
AB  - 1. The developing spinal cords of bullfrogs and transected cords of stage IV
      tadpoles were subjected to two-dimensional gel electrophoresis and histological
      analysis. During development, the level of actin, alpha-tubulin or beta-tubulin
      in the 7-10th spinal segments increased with time and reached a maximum around
      stage XIII followed by a decrease, as shown from quantitative assay on protein
      spots of 2-dimensional gels of cord homogenates. In contrast, the level of 68 kD
      neurofilament subunit (NF68) was low in tadpoles but high in frog. 2. Following a
      complete transection made at the level of the 8th spinal segment, the cord tissue
      of the lesion zone degenerated; regeneration from each cut end then occurred,
      which lengthened for approximate 0.35 mm by 28 days after transection. The
      content of actin, alpha-tubulin and beta-tubulin in the cord within 1-2 mm of the
      transection site was elevated to 124-192% of control values 7-28 days post
      transection, whereas NF68 declined to near non-detectable extent. 3. The
      regeneration of each cord stump included outgrowth of neuroepithelial cells and
      nerve fibers, reconstituting a newly regenerated cord segment. Ultrastructural
      examination revealed that features of the regrowth of fibers and guidance of
      neuroepithelial cells to the axonal growth resembled that seen in the developing
      cord. Thus the biochemical and morphological data support that the regeneration
      of the nervous system recaptulates its developmental events, providing evidence
      for molecular mechanism underlying central axonal regeneration.

PMID- 8565049
TI  - The amphiphilic peptide adenoregulin enhances agonist binding to A1-adenosine
      receptors and [35S]GTP gamma S to brain membranes.
AB  - 1. Adenoregulin is an amphilic peptide isolated from skin mucus of the tree frog,
      Phyllomedusa bicolor. Synthetic adenoregulin enhanced the binding of agonists to
      several G-protein-coupled receptors in rat brain membranes. 2. The maximal
      enhancement of agonist binding, and in parentheses, the concentration of
      adenoregulin affording maximal enhancement were as follows: 60% (20 microM) for
      A1-adenosine receptors, 30% (100 microM) for A2a-adenosine receptors, 20% (2
      microM) for alpha 2-adrenergic receptors, and 30% (10 microM) for 5HT1A
      receptors. High affinity agonist binding for A1-, alpha 2-, and 5HT1A-receptors
      was virtually abolished by GTP gamma S in the presence of adenoregulin, but was
      only partially abolished in its absence. Magnesium ions increased the binding of
      agonists to receptors and reduced the enhancement elicited by adenoregulin. 3.
      The effect of adenoregulin on binding of N6-cyclohexyladenosine ([3H]CHA) to A1
      receptors was relatively slow and was irreversible. Adenoregulin increased the
      Bmax value for [3H]CHA binding sites, and the proportion of high affinity states,
      and slowed the rate of [3H]CHA dissociation. Binding of the A1-selective
      antagonist, [3H]DPCPX, was maximally enhanced by only 13% at 2 microM
      adenoregulin. Basal and A1-adenosine receptor-stimulated binding of [35S]GTP
      gamma S were maximally enhanced 45% and 23%, respectively, by 50 microM
      adenoregulin. In CHAPS-solubilized membranes from rat cortex, the binding of both
      [3H]CHA and [3H]DPCPX were enhanced by adenoregulin. Binding of [3H]CHA to
      membranes from DDT1 MF-2 cells was maximally enhanced 17% at 20 microM
      adenoregulin. In intact DDT1 MF-2 cells, 20 microM adenoregulin did not
      potentiate the inhibition of cyclic AMP accumulation mediated via the adenosine
      A1 receptor. 4. It is proposed that adenoregulin enhances agonist binding through
      a mechanism involving enhancement of guanyl nucleotide exchange at G-proteins,
      resulting in a conversion of receptors into a high affinity state complexed with
      guanyl nucleotide-free G-protein.

PMID- 8565050
TI  - Block by 5-hydroxytryptamine of neuronal acetylcholine receptor channels
      expressed in Xenopus oocytes.
AB  - 1. Effects of 5-hydroxytryptamine (5-HT) on neuronal nicotinic acetylcholine
      (ACh) receptor channels were investigated by expressing cloned channel subunits
      in Xenopus oocytes. 2. When channels were expressed with a combination of alpha 3
      and beta 4 subunits, 5-HT (10 to 300 microM) reversibly inhibited an inward
      current activated by 100 microM ACh in a concentration-dependent manner. The
      inhibition was also observed when alpha 3 subunit was combined with beta 2
      subunit instead of beta 4 subunit, or beta 4 subunit was combined with alpha 2 or
      alpha 4-1 subunit instead of alpha 3 subunit to express channels. 3. Compounds
      known to antagonize at 5-HT receptors (LY53857, metoclopramide and propranolol)
      exhibited an agonistic effect: they inhibited the ACh-activated current. 4. The
      results suggest that 5-HT inhibits recombinant neuronal nicotinic receptor
      channels through a binding-site distinct from conventional 5-HT receptors. The
      binding-site may not be attributed to a unique type of channel subunits.

PMID- 8565051
TI  - Localization of choline acetyltransferase-expressing neurons in the larval visual
      system of Drosophila melanogaster.
AB  - Choline acetyltransferase (ChAT) is the enzyme catalyzing the biosynthesis of
      acetylcholine and is considered to be a phenotypically specific marker for
      cholinergic neurons. We have examined the distribution of ChAT-expressing neurons
      in the larval nervous system of Drosophila melanogaster by three different but
      complementary techniques: in situ hybridization with a cRNA probe to ChAT
      messenger RNA, immunocytochemistry using a monoclonal anti-ChAT antibody, and X
      gal staining of transformed animals carrying a reporter gene composed of 7.4 kb
      of 5' flanking DNA from the ChAT gene fused to a lacZ reporter gene. All three
      techniques demonstrated ChAT-expressing neurons in the larval visual system. In
      embryos, the photoreceptor organ (Bolwig's organ) exhibited strong cRNA
      hybridization signals. The optic lobe of late third-instar larvae displayed ChAT
      immunoreactivity in Bolwig's nerve and a neuron close to the insertion site of
      the optic stalk. This neuron's axon ran in parallel with Bolwig's nerve to the
      larval optic neuropil. This neuron is likely to be a first-order interneuron of
      the larval visual system. Expression of the lacZ reporter gene was also detected
      in Bolwig's organ and the neuron stained by anti-ChAT antibody. Our observations
      indicate that acetylcholine may be a neurotransmitter in the larval photoreceptor
      cells as well as in a first-order interneuron in the larval visual system of
      Drosophila melanogaster.

PMID- 8565052
TI  - Norepinephrine-induced phosphorylation of the transcription factor CREB in
      isolated rat pinealocytes: an immunocytochemical study.
AB  - In the present study we investigated whether norepinephrine, which stimulates
      melatonin biosynthesis in the mammalian pineal organ, causes phosphorylation of
      the cyclic AMP responsive element binding protein (CREB) in rat pinealocytes.
      Cells isolated from the pineal organ of adult male rats and cultured on coated
      coverslips were treated with norepinephrine, beta- or alpha 1-adrenergic agonists
      for 12, 5, 10, 20, 30, 60 or 300 min and then immunocytochemically analyzed with
      an antibody against phosphorylated CREB (p-CREB). Treatment with norepinephrine
      or beta-adrenergic agonists resulted in a similar, time-dependent induction of p
      CREB immunoreactivity, exclusively found in cell nuclei. The alpha 1-adrenergic
      agonist phenylephrine did not induce p-CREB immunoreactivity at low doses (0.1
      microM) or when high doses (10 microM) were applied in combination with a beta
      antagonist (propranolol, 0.1 microM). This indicates that induction of CREB
      phosphorylation is elicited by beta-adrenergic receptor stimulation. The response
      was first seen after 10 min and reached a maximum after 30 to 60 min when more
      than 90% of the cells displayed p-CREB immunoreactivity. The intensity of the p
      CREB immunoreactivity showed marked cell-to-cell variation, but nearly all
      immunoreactive cells were identified as pinealocytes by double-labeling with an
      antibody against the S-antigen, a pinealocyte-specific marker. The results show
      that norepinephrine stimulation induces p-CREB immunoreactivity by acting upon
      beta-adrenergic receptors in virtually all rat pinealocytes. The findings support
      the notion that phosphorylation of CREB is a rather rapid and uniform response of
      pinealocytes to noradrenergic stimulation and thus is an important link between
      adrenoreceptor activation and subsequent gene expression in the rat pineal organ.

PMID- 8565053
TI  - Activin A and transforming growth factor-beta stimulate heart formation in
      axolotls but not rescue cardiac lethal mutants.
AB  - In the Mexican axolotl (salamander), Ambystoma mexicanum, a recessive cardiac
      lethal mutation causes an incomplete differentiation of the myocardium. Mutant
      hearts lack organized sarcomeric myofibrils and do not contract throughout their
      lengths. We have previously shown that RNA purified from normal anterior endoderm
      or from juvenile heart tissue is able to rescue mutant embryonic hearts in an in
      vitro organ culture system. Under these conditions as many as 55% of formerly
      quiescent mutant hearts initiate regular contractions within 48 hours. After
      earlier reports that transforming growth factor-beta 1 and, to a lesser extent,
      platelet-derived growth factor-BB could substitute for anterior endoderm as a
      promoter of cardiac mesodermal differentiation in normal axolotl embryos, we
      decided to examine the effect of growth factors in the cardiac mutant axolotl
      system. In one type of experiment, stage 35 mutant hearts were incubated in
      activin A, transforming growth factors-beta 1 or beta 2, platelet-derived growth
      factor, or epidermal growth factor, but no rescue of mutant hearts was achieved.
      Considering the possibility that growth factors would only be effective at
      earlier stages of development, we tested transforming growth factors-beta 1 and
      beta 5, and activin A on normal and mutant precardiac mesoderm explanted in the
      absence of endoderm at neurula stage 14. We found that, although these growth
      factors stimulated heart tube formation in both normal and mutant mesoderm
      explants, only normal explants contained contractile myocardial tissue. We
      hypothesize that transforming growth factor-beta superfamily peptides initiate a
      cascade of responses in mesoderm that result in both changes in cell shape (the
      basis for heart morphogenesis) and terminal myocardial cytodifferentiation. The
      cardiac lethal mutation appears to be deficient only in the latter process.

PMID- 8565054
TI  - Fine structure and primary sensory projections of sensilla located in the
      sacculus of the antenna of Drosophila melanogaster.
AB  - Sensilla lining the inner walls of the sacculus on the third antennal segment of
      Drosophila melanogaster were studied by light and transmission electron
      microscopy. The sacculus consists of three chambers: I, II and III. Inside each
      chamber morphologically distinct groups of sensilla having inflexible sockets
      were observed. Chamber I contains no-pore sensilla basiconica (np-SB). The lumen
      of all np-SB are innervated by two neurons, both resembling hygroreceptors.
      However, a few np-SB contain one additional neuron, presumed to be
      thermoreceptive. Chamber II houses no-pore sensilla coeloconica (np-SC). All np
      SC are innervated by three neurons. The outer dendritic segments of two of these
      neurons fit tightly to the wall of the lumen and resemble hygroreceptor neurons.
      A third, more electron-dense sensory neuron, terminates at the base of the
      sensillum and resembles a thermoreceptor cell. Chamber III of the sacculus is
      divided into ventral and dorsal compartments, each housing morphologically
      distinct grooved sensilla (GS). The ventral compartment contains thick GS1, and
      the dorsal compartment has slender sensilla GS2. Ultrastructurally, both GS1 and
      GS2 are double-walled sensilla with a longitudinal slit-channel system and are
      innervated by two neurons. The dendritic outer segment of one of the two neurons
      innervates the lumen of the GS and branches. On morphological criteria, we infer
      this neuron to be olfactory. The other sensory neuron is probably
      thermoreceptive. Thus, the sacculus in Drosophila has sensilla that are
      predominantly involved in hygroreception, thermoreception, and olfaction. We have
      traced the sensory projections of the neurons innervating the sacculus sensilla
      of chamber III using cobaltous lysine or ethanolic cobalt (II) chloride. The
      fibres project to the antennal lobes, and at least four glomeruli (VM3, DA3 and
      DL2-3) are projection areas of sensory neurons from these sensilla. Glomerulus
      DL2 is a common target for the afferent fibres of the surface sensilla
      coeloconica and GS, whereas the VM3, DA3 and DL3 glomeruli receive sensory fibres
      only from the GS.

PMID- 8565055
TI  - The tympanal hearing organ of a fly: phylogenetic analysis of its morphological
      origins.
AB  - A key adaptation for any parasitoid insect is the sensory modality that it uses
      to locate its host insect. All members of the speciose family Tachinidae
      (Diptera) are parasitoids, but only flies of the tribe Ormiini use acoustic cues
      to find their hosts. Ormiine flies are parasitoids of various genera of crickets
      and katydids. Gravid females of one ormiine species, Ormia ochracea, hear the
      reproductive calling song of male field crickets and home in on those calls to
      locate their hosts. While many flies possess various kinds of "ears" to detect
      airborne sounds, only ormiine flies have been reported to possess true tympanal
      hearing organs. Such organs are well-known to occur in their cricket and katydid
      hosts. The ormiine ear is an evolutionary innovation within Diptera. Our
      objective was to trace the phylogenetic origins of the tympanal hearing organ
      among higher flies. Since the ormiine hearing organ is a complex organ within the
      prothorax, we examined possible precursor structures in the prothoraces of
      selected Diptera. We have uncovered a suite of characters that define the ormiine
      ear. These characters in the prothorax include a pair of prosternal tympanal
      membranes, a pair of chordotonal sensory organs, and modifications of the
      tracheal system. We have been able to identify and trace the presumptive homologs
      of these ormiine characters through selected species of related Diptera, using
      the method of outgroup comparison.

PMID- 8565056
TI  - Monoclonal antibody raised against murine IL-1 alpha peptide cross-reacts with a
      60-kDa antigen in early Drosophila melanogaster embryo.
AB  - Whole-mounts of Drosophila embryos were stained with the monoclonal antibody Vmp
      18, raised against the peptide 199-208 of murine interleukin 1/ alpha.
      Immunofluorescence observations showed that the antibody cross-reacted with an
      antigenic determinant that changed in localization during Drosophila development.
      In syncytial Drosophila embryos, the antibody recognized an epitope localized on
      the nuclear envelope throughout mitotic division. As cellularization occurred,
      the fluorescence was mainly concentrated in the apical region of the blastoderm
      cells. Western blot analysis of whole Drosophila embryo extracts showed that the
      antibody recognized a 60-kDa protein in syncytial embryos and during germ band
      elongation. This suggests that the 60-kDa antigen undergoes dynamic
      redistribution during embryogenesis.

PMID- 8565057
TI  - The endolymphatic duct and sac of the rat: a histological, ultrastructural, and
      immunocytochemical investigation.
AB  - A study of the ultrastructure, vascularization, and innervation of the
      endolymphatic duct and sac of the rat has been performed by means of light- and
      electron-microscopic and immunocytochemical methods. Two different types of
      epithelial cells have been identified: the ribosome-rich cell and the
      mitochondria-rich cell. These two cell types make up the epithelium of the
      complete endolymphatic duct and sac, although differences in their quantitative
      distribution exist. The morphology of the ribosome-rich cells varies between the
      different parts of the endolymphatic duct and sac; the morphology of the
      mitochondria-rich cells remains constant. According to the epithelial
      composition, vascularization, and structural organization of the lamina propria,
      both duct and sac are subdivided into three different parts. A graphic
      reconstruction of the vascular network supplying the endolymphatic duct and sac
      shows that the vascular pattern varies among the different parts. In addition,
      the capillaries of the duct are of the continuous types, whereas those supplying
      the sac are of the fenestrated type. Nerve fibers do not occur within the
      epithelium of the endolymphatic duct and sac. A few nerve fibers regularly occur
      in the subepithelial compartment close to the blood vessels; these fibers have
      been demonstrated in whole-mount preparations by the application of the neuronal
      marker protein gene product 9.5. Single beaded fibers immunoreactive to substance
      P and calcitonin-gene related peptide are observed within the same compartment.
      Dopamine-beta-hydroxylase-immunoreactive axons are restricted to the walls of
      arterioles. Morphological differences between the different portions of the
      endolymphatic duct and sac are discussed with regard to possible roles in fluid
      absorption and immunocompetence.

PMID- 8565058
TI  - Redistribution of cell membrane probes following contraction-induced injury of
      mouse soleus muscle.
AB  - Our aim was to study how mouse skeletal muscle membranes are altered by eccentric
      and isometric contractions. A fluorescent dialkyl carbocyanine dye (DiOC18(3))
      was used to label muscle membranes, and the membranes accessible to the dye were
      observed by confocal laser scanning microscopy. Experiments were done on normal
      mouse soleus muscles and soleus muscles injured by 20 eccentric or 20 isometric
      contractions. Longitudinal optical sections of control muscle fibers revealed
      DiOC18(3) staining of the plasmalemma and regularly spaced transverse bands
      corresponding in location to the T-tubular system. Transverse optical sections
      showed an extensive reticular network with the DiOC18(3) staining. Injured muscle
      fibers showed distinctively different staining patterns in both longitudinal and
      transverse optical sections. Longitudinal optical sections of the injured fibers
      revealed staining in a longitudinally-oriented pattern. No correlations were
      found between the abnormal DiOC18(3) staining and the reductions in maximal
      isometric tetanic force or release of lactate dehydrogenase (P > or = 0.32).
      Additionally, no difference in the extent of abnormal staining was found between
      muscles performing eccentric contractions and those performing the less damaging
      isometric contractions. However, many fibers in muscles injured by eccentric
      contractions showed swollen regions with marked loss of membrane integrity and an
      elevated free cytosolic calcium concentration as observed in Fluo-3 images. In
      conclusion, a loss of cell membrane integrity results from contractile activity,
      enabling DiOC18(3) staining of internal membranes. The resulting staining pattern
      is striking and fibers with damaged cell membranes are easily distinguished from
      uninjured ones.

PMID- 8565059
TI  - FMRFamide is endogenous to the Aplysia heart.
AB  - The presence of the molluscan neuropeptide FMRFamide was investigated in the
      heart of the sea hare, Aplysia californica. Immunohistochemical localization and
      high performance liquid chromatography (HPLC) coupled with radioimmunoassays of
      HPLC fractions were used to demonstrate the presence of FMRFamide and FLRFamide
      in the heart. FMRFamide-immunoreactive (FMRFamide-IR) nerve fibers, varicosities,
      and neuronal somata were observed in whole-mounts of the hearts. The atrium and
      atrioventricular (AV) valve regions contained significantly higher densities (P <
      0.05, ANOVA) of immunoreactive varicosities compared to the ventricle. The high
      density of FMRFamide-IR varicosities in the atrium and the lack of sensitivity of
      this region to FMRFamide suggest that the atrium may be a neurohemal organ for
      the release of FMRFamide. The presence of FMRFamide-IR somata in the Aplysia
      heart suggests that peripheral neurons may play a role in modifying heart
      activity, independent of the central nervous system.

PMID- 8565060
TI  - G protein heterodimers: new structures propel new questions.

PMID- 8565061
TI  - Chromatin structure and RNA polymerase II connection: implications for
      transcription.

PMID- 8565062
TI  - How do bacteria decide where to divide?

PMID- 8565063
TI  - Septin scaffolds and cleavage planes in Saccharomyces.

PMID- 8565064
TI  - How fission yeast fission in the middle.
AB  - In fission yeast, we propose that the division plane may be positioned by the
      position of the premitotic nucleus, perhaps by a signal emanating from the
      nucleus. Gene products involved in the assembly of the ring and its temporal and
      spatial controls are beginning to be characterized. Some of these, such as mid1p,
      may be involved in signals that position the division site. In animal cells, the
      division site may be determined by analogous signals emanating from the mitotic
      asters (Rappaport, 1986). We speculate that the signals defined in fission yeast
      will help identify signals that determine the division plane in all kinds of
      eukaryotes.

PMID- 8565065
TI  - Cleavage plane specification in C. elegans: how to divide the spoils.

PMID- 8565066
TI  - The DExH box protein Suv3p is a component of a yeast mitochondrial 3'-to-5'
      exoribonuclease that suppresses group I intron toxicity.
AB  - The yeast mitochondrial protein Suv3p is a putative NTP-dependent RNA helicase.
      Here we report that in cells lacking Suv3p, there is an approximately 50-fold
      increase in the excised form of the group I intron omega of the mitochondrial 31S
      rRNA gene. Surprisingly, little mature 21S rRNA accumulates in those cells;
      instead, unligated 21S rRNA exons appear. Intron overaccumulation could lead to
      spliced exon reopening via a reaction known to be catalyzed by group I introns in
      vitro. We also show that Suv3p is a functional component of a novel mitochondrial
      NTP-dependent 3'-to-5' exoribonuclease activity that can degrade group I intron
      RNAs. These findings account for group I intron overaccumulation in cells lacking
      Suv3p and define a novel function for putative RNA helicases in direct RNA
      degradation.

PMID- 8565067
TI  - Beyond homing: competition between intron endonucleases confers a selective
      advantage on flanking genetic markers.
AB  - The closely related B. subtilis bacteriophages SPO1 and SP82 have similar introns
      inserted into a conserved domain of their DNA polymerase genes. These introns
      encode endonucleases with unique properties. Other intron-encoded "homing"
      endonucleases cleave both strands of intronless DNA; subsequent repair results in
      unidirectional gene conversion to the intron-containing allele. In contrast, the
      enzymes described here cleave one strand on both intron-containing and intronless
      targets at different distances from their common intron insertion site. Most
      surprisingly, each enzyme prefers DNA of the heterologous phage. The SP82-encoded
      endonuclease is responsible for exclusion of the SPO1 intron and flanking genetic
      markers from the progeny of mixed infections, a novel selective advantage
      imparted by an intron to the genome in which it resides.

PMID- 8565068
TI  - The three chemical steps of Tn10/IS10 transposition involve repeated utilization
      of a single active site.
AB  - Nonreplicative transposition by Tn10/IS10 involves three chemical steps at each
      transposon end: cleavage of the two strands plus joining of one strand to target
      DNA. These steps occur within a synaptic complex comprising two transposon ends
      and monomers of IS10 transposase. We report four transposase mutations that
      individually abolish each of the three chemical steps without affecting the
      synaptic complex. We conclude that a single constellation of residues, the
      "active site," directly catalyzes each of the three steps. Analyses of reactions
      containing mixtures of wild-type and catalysis-defective transposases indicate
      that a single transposase monomer at each end catalyzes the cleavage of two
      strands and that strand transfer is carried out by the same monomers that
      previously catalyzed cleavage. These and other data suggest that one active site
      unit carries out all three reactions in succession at one transposon end.

PMID- 8565069
TI  - RNA polymerase II holoenzyme contains SWI/SNF regulators involved in chromatin
      remodeling.
AB  - The RNA polymerase II holoenzyme contains RNA polymerase II, a subset of general
      transcription factors and SRB regulatory proteins. We report here that SWI and
      SNF gene products, previously identified as global gene regulators whose
      functions include remodeling chromatin, are also integral components of the yeast
      RNA polymerase II holoenzyme. The SWI/SNF proteins are components of the SRB
      complex, also known as the mediator, which is tightly associated with the RNA
      polymerase II C-terminal repeat domain. The SWI/SNF components provide the
      holoenzyme with the capacity to disrupt nucleosomal DNA and thus facilitate
      stable binding of various components of the transcription initiation complex at
      promoters.

PMID- 8565070
TI  - Facilitated recycling pathway for RNA polymerase III.
AB  - We show that the high in vitro transcription efficiency of yeast RNA pol III is
      mainly due to rapid recycling. Kinetic analysis shows that RNA polymerase
      recycling on preassembled tDNA.TFIIIC.TFIIIB complexes is much faster than the
      initial transcription cycle. High efficiency of RNA pol III recycling is favored
      at high UTP concentrations and requires termination at the natural termination
      signal. Runoff transcription does not allow efficient recycling. The reinitiation
      process shows increased resistance to heparin as compared with the primary
      initiation cycle, as if RNA polymerase was not released after termination.
      Indeed, template competition assays show that RNA pol III is committed to
      reinitiate on the same gene. A model is proposed where the polymerase molecule is
      directly transferred from the termination site to the promoter.

PMID- 8565071
TI  - A pre-mRNA-binding protein accompanies the RNA from the gene through the nuclear
      pores and into polysomes.
AB  - In the larval salivary glands of C. tentans, it is possible to visualize by
      electron microscopy how Balbiani ring (BR) pre-mRNA associates with proteins to
      form pre-mRNP particles, how these particles move to and through the nuclear
      pore, and how the BR RNA is engaged in the formation of giant polysomes in the
      cytoplasm. Here, we study C. tentans hrp36, an abundant protein in the BR
      particles, and establish that it is similar to the mammalian hnRNP A1. By immuno
      electron microscopy it is demonstrated that hrp36 is added to BR RNA concomitant
      with transcription, remains in nucleoplasmic BR particles, and is translocated
      through the nuclear pore still associated with BR RNA. It appears in the giant BR
      RNA-containing polysomes, where it remains as an abundant protein in spite of
      ongoing translation.

PMID- 8565072
TI  - A novel complex of nucleoporins, which includes Sec13p and a Sec13p homolog, is
      essential for normal nuclear pores.
AB  - In a genetic screen for nucleoporin-interacting components, a novel nuclear pore
      protein Nup84p, which exhibits homology to mammalian Nup107p, was isolated.
      Nup84p forms a complex with five proteins, of which Nup120p, Nup85p, Sec13p, and
      a Sec13p homolog were identified. Upon isolation of Sec13p-ProtA, nucleoporins
      were still associated, but the major copurifying band was a 150 kDa protein,
      showing that Sec13p occurs in two complexes. Disruption of any of the genes
      encoding Nup84p, Nup85p, or Nup120p caused defects in nuclear membrane and
      nuclear pore complex organization, as well as in poly(A)+ RNA transport. Thus,
      the Nup84p complex in conjunction with Sec13-type proteins is required for
      correct nuclear pore biogenesis.

PMID- 8565073
TI  - Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated
      endocytosis.
AB  - Binding of alpha factor to Ste2p, a G protein-coupled plasma membrane receptor,
      activates a signal transduction pathway and stimulates endocytosis of the
      receptor-ligand complex. Ligand binding also induces ubiquitination of the Ste2p
      cytoplasmic tail. Protein ubiquitination is required for stimulated endocytosis
      of Ste2p, as internalization is 5- to 15-fold slower in ubc mutants that lack
      multiple ubiquitin-conjugating enzymes. In a C-terminal truncated form of Ste2p
      that is rapidly ubiquitinated and endocytosed in response to ligand binding, a
      single lysine to arginine substitution in its cytoplasmic tail eliminates both
      ubiquitination and internalization. Thus, ubiquitination of Ste2p itself is
      required for ligand-stimulated endocytosis. We propose that ubiquitination
      mediates degradation of receptor-ligand complexes, not via the proteasome, but by
      acting as a signal for endocytosis leading to subsequent degradation in the
      lysosome/vacuole.

PMID- 8565074
TI  - Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von
      Willebrand factor.
AB  - We have identified two distinct mechanisms initiating the adhesion of flowing
      platelets to thrombogenic surfaces. The intergrin alpha IIb beta 3 promotes
      immediate arrest onto fibrinogen but is fully efficient only at wall shear rates
      below 600-900 s-1, perhaps because of a relatively slow rate of bond formation or
      low resistance to tensile stress. In contrast, glycoprotein Ib alpha binding to
      immobilized von Willebrand factor (vWF) appears to have fast association and
      dissociation rates as well as high resistance to tensile stress, supporting slow
      movement of platelets in continuous contact with the surface even at shear rates
      in excess of 6000 s-1. This eventually allows activated alpha IIb beta 3 to
      arrest platelets onto vWF under conditions not permissive of direct binding to
      fibrinogen. The coupling of these different functions may be crucial for
      thrombogenesis.

PMID- 8565075
TI  - TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal
      transduction pathways.
AB  - Tumor necrosis factor (TNF) can induce apoptosis and activate NF-kappa B through
      signaling cascades emanating from TNF receptor 1 (TNFR1). TRADD is a TNFR1
      associated signal transducer that is involved in activating both pathways. Here
      we show that TRADD directly interacts with TRAF2 and FADD, signal transducers
      that activate NF-kappa B and induce apoptosis, respectively. A TRAF2 mutant
      lacking its N-terminal RING finger domain is a dominant-negative inhibitor of TNF
      mediated NF-kappa B activation, but does not affect TNF-induced apoptosis.
      Conversely, a FADD mutant lacking its N-terminal 79 amino acids is a dominant
      negative inhibitor of TNF-induced apoptosis, but does not inhibit NF-kappa B
      activation. Thus, these two TNFR1-TRADD signaling cascades appear to bifurcate at
      TRADD.

PMID- 8565076
TI  - Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor
      neuron-dependent step in interneuron differentiation.
AB  - Motor neuron differentiation is accompanied by the expression of a LIM
      homeodomain transcription factor, Islet1 (ISL1). To assess the involvement of
      ISL1 in the generation of motor neurons, we analyzed cell differentiation in the
      neural tube of embryos in which ISL1 expression has been eliminated by gene
      targeting. Motor neurons are not generated without ISL1, although many other
      aspects of cell differentiation in the neural tube occur normally. A population
      of interneurons that express Engrailed1 (EN1), however, also fails to
      differentiate in Isl1 mutant embryos. The differentiation of EN1+ interneurons
      can be induced in both wild-type and mutant neural tissue by regions of the
      neural tube that contain motor neurons. These results show that ISL1 is required
      for the generation of motor neurons and suggest that motor neuron generation is
      required for the subsequent differentiation of certain interneurons.

PMID- 8565078
TI  - [Evaluation of the beta-adrenergic receptor agonists].

PMID- 8565077
TI  - AML1, the target of multiple chromosomal translocations in human leukemia, is
      essential for normal fetal liver hematopoiesis.
AB  - The AML1-CBF beta transcription factor is the most frequent target of chromosomal
      rearrangements in human leukemia. To investigate its normal function, we
      generated mice lacking AML1. Embryos with homozygous mutations in AML1 showed
      normal morphogenesis and yolk sac-derived erythropoiesis, but lacked fetal liver
      hematopoiesis and died around E12.5. Sequentially targeted AML1-/-es cell
      retained their capacity to differentiate into primitive erythroid cells in vitro;
      however, no myeloid or erythroid progenitors of definitive hematopoietic origin
      were detected in either the yolk sac or fetal livers of mutant embryos. Moreover,
      this hematopoietic defect was intrinsic to the stem cells in that AML1-/-ES cells
      failed to contribute to hematopoiesis in chimeric animals. These results suggest
      that AML1-regulated target genes are essential for definitive hematopoiesis of
      all lineages.

PMID- 8565079
TI  - [Peak expiratory flow rate (PEF) and serum eosinophil cationic protein (ECP)
      changes in nocturnal asthmatics].
AB  - We have investigated the serum ECP and peak expiratory flow rate in 20 patients
      with nocturnal asthma. Changes of PEF were measured in every 2 hours around the
      whole day, and the blood samples were obtained at 4:00 and 16:00 to measure the
      serum ECP level and the peripheral Eo numbers. In addition, 10 asthmatics as well
      as normal subjects received methacholine challenge at 4:00 and 16:00. It was
      found that the PEF reached the lowest point at 4:00 and obviously less than that
      at 16:00 (187.50 +/- 120.31 L/min vs 313.00 +/- 108.14 L/min, P < 0.05), that the
      airway reactivity at 4:00 was significantly higher than at 16:00 (P < 0.05) and
      the difference of MCH-PC20 between the two time points was 0.34 +/- 0.31 mg/ml,
      that the serum ECP level at 4:00 was obviously higher than that at 16:00 (11.14
      +/- 7.40 micrograms/ml vs 5.49 +/- 4.12 micrograms/ml, P < 0.05). The change rate
      of PEF markedly related to the change of serum ECP between the two time points (r
      = 0.61, P < 0.05). The findings suggested that the activation of Eo and its
      release of ECP might be effect of the circadian-rhythmic change of pulmonary
      functions in nocturnal asthma.

PMID- 8565080
TI  - [The relationship between H2 receptor of airways and the pathogenesis of
      bronchial asthma].
AB  - In order to explore the relationship between H2 R and the pathogenesis of asthma,
      we treated 19 stable asthmatic patients with H2-receptor agonist impromidine and
      observed its effect on bronchial hyperresponsiveness (BHR). The results showed
      that single dose inhalation of impromidine (2.5mg, in 13 cases) had no effect on
      the starting respiratory resistance (Rrs) and the minimum amount of cumulative
      dose (Dmin) to asthmatic airways, while repetitive inhalation of impromidine for
      10 days (2. 5mg a day, in 6 cases) decreased the Rrs (P = 0.059) and increased
      the Dmin significantly (P < 0.05); and that H2R agonist impromidine could reduce
      the sensitivity of airway to methacholine and improve the BHR of asthmatic
      patients. The results suggest that H2R agonist may be used as anti-inflammatory
      drug to treat asthma and H2R may have protective role in the inflammatory
      reaction of asthmatic airways.

PMID- 8565081
TI  - [Effects of the potassium channel activator cromakalim on human isolated
      bronchial smooth muscle].
AB  - The method which can be used to measure human small smooth muscle function in
      vitro with the bronchiolar strip preparation was described. The aim of the
      present study was to investigate the effect of cromakalim against histamine
      acetylcholine, prostaglandin F2 alpha in human isolated bronchiolar smooth
      muscle. The results showed the order of relaxant potencies was cromakalim >
      salbutamol > Theophylline. The relaxation responses to cromakalim, salbutamol,
      theophylline for histamine or prostaglandin F2 alpha were not significantly
      different. The relaxation responses to cromakalim, salbutamol, theophylline for
      acetylcholine were significantly different. Cromakalim was more potent and more
      effective than salbutamol and theophylline. Cromakalim was able to produce an
      additional relaxation response in the presence of a maximal relaxation induced by
      salbutamol and theophylline.

PMID- 8565082
TI  - [Treating steroids dependent asthmatic patients with high dose beclomethasone
      dipropionate aerosol].
AB  - In order to provide a more effective alternative therapy for the steroid
      dependent asthmatic (SDA) patients, 23 SDA patients replaced their oral steroids
      with high dose beclomethasone dipropionate (1500 micrograms/d) inhalation were
      investigated. The changes of clinical features, pulmonary function and the
      Synacthen test were recorded. The results showed that about 82% of the patients
      replaced their oral steroids completely or partially with the inhalation therapy,
      the clinical features were improved in 13% of the patients and the failure rate
      was only 4.4%, the results also revealed that, after replacement, the pulmonary
      function of the patients were improved (P < 0.05); according to the results of
      Synacthen test, after alternative therapy for 3-6 months, the damaged reserve
      power and secretive ability of adrenal cortex of the patients were also partially
      improved (P < 0.01).

PMID- 8565084
TI  - [Human basophil degranulation test (HBDT) in fungal allergic asthmatic patients].
AB  - The authors recommand the methodology of HBDT for testing fungal allergens, pH
      7.6, 37 degrees C and 10 mg/ml are the most suitable experimental conditions. The
      positive rate of HBDT in allergic asthmatic patients is 91.7%, and correlated
      very well with the results of skin tests. The degranulation index (DI) in
      allergic asthma is significantly higher than that in normals (P < 0.001). The DI
      after one year's desensitization treatment with fungal allergens is markedly
      lowered than before (P < 0.001). The results suggest that HBDT is a simple,
      reliable and precise method to investigate allergens in vitro and also reflects
      the function of basophils in asthma.

PMID- 8565083
TI  - [Inhalation of platelet-activating factor induced guinea pig airway
      hyperresponsiveness: role of eosinophils activation].
AB  - Exposure of guinea pigs to aerosols of 200 micrograms/ml platelet-activating
      factor 24 h later, airway hyperresponsiveness to histamine induced and number of
      eosinophils and hypodense eosinophils in bronchoalveolar lavage fluid (BALF)
      increased, comparing with the control group. The number of eosinophils in BALF
      was corelated with PC20 value in PAF-treated group (r = -0.62, P < 0.05).
      However, the percentage of hypodense eosinophil in BALF had closer relation to
      airway responsiveness (r = -0.84, P < 0.01). The content of peroxidase in
      hypodense eosinophils in BALF for guinea pigs treated by inhalation of PAF was
      lowered markedly than that in normodense eosinophil (P < 0.05). The result
      suggested that chemotaxis and activation of eosinophils by PAF might play an
      important role in airway hyperresponsiveness.

PMID- 8565085
TI  - [Plasma endothelin 1 and its clinical evaluation in asthma].
AB  - Plasma endothelin 1 (ET1) was determined by radioimmunoassay in 28 cases of acute
      attack of asthma (attack group), 23 subjects of non-symptomatic asthma (remission
      group) and 20 normal volunteers (control group). The results showed that the
      plasma ET1 in attack group (13.4 +/- 5.2 fmol/ml) was much higher than that in
      both remission group (8.4 +/- 3.9 fmol/ml, P < 0.01) and control group (6.6 +/-
      2.6 fmol/ml, P < 0.01). However, there was no significant difference between
      remission group and control group. The plasma ET1 level revealed notably negative
      correlation to PaO2 and FEV1% (r = -0.8257, r = -0.8157, P < 0.01). The results
      suggested that ET1 probably involved in pathophysiologic process of acute attack
      of bronchial asthma.

PMID- 8565086
TI  - [The effects of hypoxia on nitric oxide synthase activity and mRNA expression of
      pulmonary artery endothelial cells in pigs].
AB  - The aim of the study is to investigate whether hypoxia might affect nitric oxide
      synthase (NOS) activity or mRNA expression of cultured pulmonary artery
      endothelial cells in pigs by means of NADPH-diaphorase cytochemical stain and DNA
      RNA dot blot hybridization respectively. The NOS activity and mRNA expression
      were highly present in normoxic group as well as 6 and 24 hours serum-free
      control groups, but significantly lowered in 6 and 24 hours hypoxic groups. The
      mRNA expression of NOS gene was almost absent in 48 hours hypoxic cells. The
      results indicate that hypoxia can attenuate the activity and mRNA expression of
      NOS in cultured pulmonary artery endothelial cells, which may lay an important
      role in modulating acute hypoxic pulmonary vasocontriction and chronic hypoxic
      pulmonary arterial hypertension.

PMID- 8565088
TI  - [Surgical treatment of 165 cases of stage III small cell lung carcinoma].
AB  - The author analysed the effect of surgical therapy in 165 cases with stage III
      SCLC from 1979 to the end of 1991, and compared with 87 cases of combined therapy
      and 78 cases in simple operative therapy. The author also makes an observation of
      cases with pre-operative and (or) post-operative chemo- and radiation therapy.
      Their over-all 5 year survival rate was 16.6%. Stage among 5 year survival cases
      in TNM stage. IIIa was 20.4% and no for Stage IIIb. The 5 year survival of
      combined therapy was 22.8% and that of simple operative group was 7.9%. The
      result shows that in the Stage III SCLC combined therapy is superior to that of
      simple operative group. It seems that postoperative radiation and chemotherapy is
      better than pre-operative in combined therapy group. The author's opinion is that
      surgical indication of SCLC is limited to stage IIIa.

PMID- 8565087
TI  - [The study of GST mu gene deletion as the hereditary marker for susceptibility to
      lung cancer].
AB  - A total of 175 lung cancer patients and 104 controls were detected for GST mu
      gene using PCR technique. The results showed that the GST mu gene deletion rate
      in lung cancer patients was 71.4%, which was significantly higher than the
      controls, 51.9%. Analysis according to pathological classification of lung cancer
      indicated that the GST mu gene deletion rate in all three kinds of pathological
      types-squamous, adenocarcinoma and small cell carcinoma, were markedly higher
      than that of controls, especially for small cell carcinoma (the deletion sate is
      77.5%). The frequency of GST mu gene was not associated with smoking in both
      groups, but the higher deficiency rate was found in the low age group of lung
      cancer patients, showed 85.3% compared to the high age group, 68.1%. All the
      results showed that GST mu gene deletion may be an important host hereditary
      marker for susceptibility to lung cancer.

PMID- 8565089
TI  - [Chest radiograph in assessing the results of treatment with 6-month short-course
      chemotherapy of pulmonary tuberculosis].
AB  - Chest radiograph was evaluated in 287 cases of smear-positive pulmonary
      tuberculosis treated with 6-month short course chemotheapy. After 6-month
      chemotherapy was completed, the results of chest rediography were in a similar
      trend comparing to that of sputum examination in 94.0% cases. During 18 months
      follow-up in 107 (37.9%) of 282 cases, the remained shadows in chest radiography
      continued to resolve and in 14 (58%) of 24 cases, remained in chest radiograph
      were closed. It is concluded that sputum examination in assessing the results of
      6 months short-course chemotherapy simple, reliable and cheaper than chest
      radiography.

PMID- 8565091
TI  - [Brief history of Chinese Journal of Pathology in the past 40 years].

PMID- 8565090
TI  - [Comparison of in-vitro and in-vivo activities of enoxacin and ofloxacin against
      the Mycobacterium tuberculosis].
AB  - Enoxacin (ENX) showed a moderate degree of activities in vitro against
      Mycobacterium tuberculosis in modified Saunton medium and modified Lowenstein
      Jensen Medium with MICs from 1 to 8micrograms/ml. Ofloxacin (OFLX) is superior to
      ENX, with MICs from 0.5 to 2.0micrograms/ml. In terms of median survival time
      (ST50), ENX at doses both 3mg (about 150mg/kg) daily and 6mg (about 300mg/kg)
      intermittently were inactive (P > 0.05) against M. tuberculosis infection in
      mice. OFLX at the same doses all were very significantly effective (P < 0.01).

PMID- 8565092
TI  - [General aspects and progress of the etiological survey in experimental
      oncology].

PMID- 8565093
TI  - [Advances in pathology of several common seen tumors in China].

PMID- 8565094
TI  - [Retrospect and prospect of cardiovascular pathology].

PMID- 8565095
TI  - [Retrospect and prospect of respiratory pathology in China].

PMID- 8565096
TI  - [Retrospect and recent progress of pathology of hepatobiliary system].

PMID- 8565097
TI  - [Recent advances in research on pathology of pancreatic tumors].

PMID- 8565098
TI  - [Retrospect and prospect in renal pathology].

PMID- 8565099
TI  - [Recent advances in gynecological pathology in China].

PMID- 8565100
TI  - [Retrospect and prospect of pediatric pathology in China].

PMID- 8565101
TI  - [Retrospect and prospect of pathology in lympho-reticulo-endothelial system].

PMID- 8565102
TI  - [Retrospect and prospect of endocrinological pathology].

PMID- 8565103
TI  - [Retrospect and prospect of research in osteogenic tumors].

PMID- 8565104
TI  - [Review and prospects of pathology of soft tissue tumors in China].

PMID- 8565105
TI  - [Retrospect and prospect of neuropathology in China].

PMID- 8565106
TI  - [Advances in pathology of 5 endemic diseases in China].

PMID- 8565107
TI  - [Advances in pathology of infectious diseases in China].

PMID- 8565108
TI  - [Advances in the technology applied to pathology in China].

PMID- 8565109
TI  - [Some new advances in the study on p53].

PMID- 8565110
TI  - [Diarrhea, high fever, general hemorrhage, convulsion].

PMID- 8565111
TI  - High-pressure proton NMR study of lateral self-diffusion of phosphatidylcholines
      in sonicated unilamellar vesicles.
AB  - Effects of pressure on the lateral diffusion of phospholipid molecules in
      sonicated pure 1,2-dipalmitoylphosphatidylcholine (DPPC) and 1-palmitoyl-2
      oleoylphosphatidylcholine (POPC) vesicles (15 wt%) in D2O were examined using the
      high-pressure proton NMR rotating frame spin-lattice relaxation time (T1rho)
      method. Proton T1rho were measured at pressures from 1 bar to 5000 bar and at
      temperatures of 50 degrees C to 70 degrees C for DPPC and 5 degrees C to 35
      degrees C for POPC. The T(-1)1rho values were plotted as a function of the square
      root of the spin-locking field angular frequency (omega1(1/2) and the lateral
      diffusion coefficient (D) calculated from the slope. Pressure effects on lateral
      diffusion were observed in the liquid-crystalline (LC) phase. The lateral
      diffusion coefficient exhibited sharp decreases in response to the various
      pressure-induced phase transitions encountered. However, pressure had little, if
      any, effect on lateral diffusion in the pressure-induced gel I (GI) phase and
      pressure-induced interdigitated gel (Gi) phase. The activation volumes for
      diffusion were calculated from the slopes from plots of In D versus pressure for
      both DPPC (37 ml/mol at 50 degrees C, 34 ml/mol at 60 degrees C and 25 ml/mol at
      70 degrees C) and POPC (16 ml/mol at 5 degrees C, 9 ml/mol at 20 degrees C and 6
      ml/mol at 35 degrees C) sonicated vesicles in the LC phase. The activation energy
      for diffusion (Ea) was calculated using the slopes from plots of In D versus the
      inverse of the temperature (1/T) for both DPPC and POPC in the LC phase (3.5
      kcal/mol and 3.9 kcal/mol, respectively) and for both DPPC and POPC in the GI
      phase (6.0 kcal/mol and 4.4 kcal/mol, respectively). From the lateral diffusion
      coefficient and line width data pressure-temperature phase diagrams for sonicated
      pure DPPC and POPC vesicles were constructed. The values of the temperature to
      pressure equivalence of DPPC (dTm/dP) were estimated to be 22.1 degrees C/kbar
      for the LC to GI phase transition and 28.6 degrees C/kbar for the GI to Gi phase
      transition. The value of the temperature to pressure equivalence of POPC for the
      LC to GI phase transition was estimated to be 19.0 degrees C/kbar.

PMID- 8565112
TI  - Time course of oxysterol formation during in vitro oxidation of low density
      lipoprotein.
AB  - Cholesterol oxidation products (oxysterols) have been implicated in several
      aspects of atherogenesis; they affect key enzymes in cholesterol homeostasis,
      induce calcification in vascular cells and possess cytotoxic properties.
      Oxysterols are formed during oxidative modification of low density lipoprotein
      (LDL). Using a recently developed method based on isotope dilution-mass
      spectrometry, the kinetics of formation of oxysterols during oxidation of LDL by
      cupric ions or soybean lipoxygenase was studied. The same products, mainly 7- and
      5-oxygenated cholesterol, were formed by the two oxidation methods. Virtually no
      side-chain oxidized oxysterols were formed. During the oxidations, preferentially
      esterified cholesterol was consumed and consumption of polyunsaturated fatty
      acids and formation of conjugated dienes preceded the appearance of oxysterols.
      Cholesterol 7-hydroperoxides potential cytotoxins, were present in LDL oxidized
      by copper or lipoxygenase.

PMID- 8565113
TI  - Reconstitution of bacteriorhodopsin and ATP synthase from Micrococcus luteus into
      liposomes of the purified main tetraether lipid from Thermoplasma acidophilum:
      proton conductance and light-driven ATP synthesis.
AB  - The archaebacterium Thermoplasma acidophilum is cultivated at 59 degrees C in a
      medium containing sulfuric acid of pH 2. The purified bipolar membrane spanning
      main phospholipid (MPL) of this organism can be used to produce stable liposomes
      of 100-500 nm in diameter either using a French pressure cell detergent dialysis
      or sonication. Despite a potassium diffusion potential of 186 mV very low ionic
      permeability of sonicated MPL liposomes was measured using the potassium binding
      fluorescent indicator benzofuran isophthalate PBF1, which measures net K+ uptake.
      The latter also remained very low, in the presence of the K(+) ionophore
      valinomycin and palmitic acid. Addition of valinomycin and the potent uncoupler
      carbonylcyanid-p-trifluormehoxyphenyl-hydrazone (FCCP), led to a stimulation in
      potassium uptake. The rate of proton flux can be calculated from the net K(+)
      uptake. Under these conditions MPL liposomes are 1-2 orders of magnitude less
      permeable than egg yolk lecithin vesicles. The difference in proton permeability
      becomes even more pronounced with increasing temperature, examined using the
      fluorescent pH indicator pyranine. Purified bacteriorhodopsin from Halobacterium
      halobium was reconstituted into MPL liposomes in order to study the light-driven
      proton uptake in 150 mM KCl following addition of valinomycin, gramicidin, FCCP
      and Triton X-100. The light-driven proton transport into the liposomes was
      increased 30-fold by addition of valinomycin decreased by gramicidin and FCCP,
      and abolished by Triton X-100. Co-reconstituted MPL proteoliposomes containing
      bacteriorhodopsin and ATP synthase from Micrococcus luteus were capable of light
      driven ATP synthesis demonstrating the functional coupling of proton transport
      and nucleotide generation in liposomal MPL membranes.

PMID- 8565114
TI  - Aggregates of saturated phospholipids at the air-water interface.
AB  - Surface viscosities of phospholipid/steroid mixtures at the air-water interface
      were measured by means of an oscillating pendulum. Phospholipids studied included
      1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC); 1,2-dipalmitoyl-sn-glycero-3
      phosphodimethylethanolamine (DPPDME); 1,2-dipalmitoyl-sn-glycero-3
      phosphomonomethylethanolamine (DPPMME); 1,2-dipalmitoyl-sn-glycero-3
      phosphoethanolamine (DPPE); 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1
      glycerol)] (DPPG); 1-palmitoyl-2-elaidyl-sn-glycero-3-phosphocholine and 1
      palmitoyl-2-linelaidyl-sn-glycero-3-phosphocholine. Each saturated phospholipid
      was studied in the presence of cholesterol, DPPC was also investigated in the
      presence of 5-androsten-3beta-ol; cholestanol; 5-cholestene;5alpha-cholesten
      3beta-ol methyl ether; coprostanol; 7,(5alpha)-cholesten-3beta-ol; desmosterol;
      epicholestanol; lanosterol and lophenol. The surface viscosities of the trans
      unsaturated phosphatidylcholines (PC) were undetectable by this method and in
      this respect they resembled cis- unsaturated PC. The surface viscosities of
      saturated phospholipids were very high but were reduced by low concentrations of
      steroids. Interpretation of the results for DPPC/cholesterol mixtures indicates
      that DPPC functions at the air-water interface as a one-dimensional linear
      aggregate. At 50 mN/m and 22 degrees C the average structure contains
      approximately 300 DPPC molecules. DPPDME acts similarly but DPPMME, DPPE and DPPG
      differ from DPPC in their response to cholesterol. All of the steroids examined
      except 5-androsten-3beta-ol and the lanosterol mixture paralleled cholesterol in
      their interaction with DPPC an indication that phospholipid/steroid interactions
      modifying surface viscosity have less stringent requirements for the steroid
      structure than interactions measured as condensation in surface area.

PMID- 8565115
TI  - Surfactant lipids containing aromatic units produce vesicular membranes with high
      thermal stability.
AB  - Six new vesicle-forming, cationic surfactant lipids are synthesized. Four of them
      contain 'flat' aromatic units at different locations of hydrophobic segments. In
      order to estimate the influence of aromatic units in the lipid monomer two other
      surfactant lipids of related structure with n-butyloxy units in the places of
      aromatic groups were also prepared. Transmission electron microscopy confirmed
      the vesicular membrane formation from these newly synthesized lipids. DSC or
      temperature-dependent keto-enol tautomerism of benzoylacetanilide-doped vesicles
      reveal a remarkable increase in the thermal stability of the membranes formed
      from aromatic surfactant lipids in contradistinction to their counterparts that
      contain n-butyloxy units. The enhanced thermal stability originates presumably as
      a consequence of inter-monomer stacking.

PMID- 8565116
TI  - Stimulation of repair replication by 3-aminobenzamide in human fibroblasts with
      ligase I deficiency.
AB  - A cell line deficient in DNA ligase I and sensitive to poly(ADP-ribose)
      inhibitors, 46BR, was used to examine the relationship between DNA ligation and a
      large stimulation of repair replication that is seen in cells grown in a poly(ADP
      ribose) polymerase inhibitor, 3-aminobenzamide (3AB), after exposure to
      alkylating agents. Repair replication was stimulated at least 10-fold by 3AB in
      both normal and ligase-deficient cells. Despite increased 3AB toxicity, repair
      replication in ligase I-deficient cells was unchanged from that in normal cells.
      This evidence is consistent with previous observations that the enhancement of
      repair replication by 3AB is not a direct function of DNA break frequencies. The
      stimulation may instead result from alkylation damage to other cellular
      organelles that release nucleases that cause additional damage to DNA, which
      cells attempt to repair.

PMID- 8565117
TI  - Induction of 8-hydroxydeoxyguanosine in DNA by chromium(III) plus hydrogen
      peroxide and its prevention by scavengers.
AB  - The capability of Cr(III) to induce DNA lesions generated by oxidative damage was
      investigated in this study by examining the formation of 8-hydroxydeoxyguanosine
      (8-OHdG) in calf thymus DNA by CrCl3 and/or H2O2 in 10 mM phosphate buffer. In
      the presence of 0.5 mM H2O2, the formation of 8-OHdG markedly increased with
      increasing CrCl3 concentration. In contrast, H2O2 or CrCl3 alone did not cause
      any increase in 8-OHdG level above background. The amount of 8-OHdG induced by
      CrCl3 plus H2O2 was time dependent; its generation increased linearly over an
      incubation period of 90 min. The formation of 8-OHdG was unfavorable in an acidic
      solution (pH < 6); the highest level of 8-OHdG was observed at pH 7-8. Scavengers
      of reactive oxygen species markedly inhibited the formation of 8-OHdG by CrCl3
      plus H2O2; the inhibition effect was sodium azide > D-mannitol > Tris-HCl at an
      equal concentration. The induction of 8-OHdG by CrCl3 plus H2O2 remained
      unchanged in D2O. Moreover, an addition of catalase (2.2 U/ml) to the reaction
      mixture completely inhibited the formation of 8-OHdG by CrCl3/H2O2, whereas only
      22% of that formation was inhibited by superoxide dismutase (11 U/ml). A large
      amount of bovine serum albumin (1.1 mg/ml) could reduce the formation of 8-OHdG
      by CrCl3 plus H2O2, thereby implying that Cr(III)-mediated DNA-protein crosslinks
      are unfavorable for 8-OHdG formation. Furthermore, ascorbate could prevent the
      formation of 8-OHdG by CrCl3 plus H2O2; the extent of prevention increased with
      increasing ascorbate concentration (10 microM-3 mM). Thus, ascorbate acts as a
      free radical scavenger in the CrCl3/H2O2 system. The above findings suggest that
      Cr(III)/H2O2 could generate oxidative damage to DNA, possibly through a Fenton
      like reaction, i.e. Cr(III)+H2O2-->Cr(IV)+.OH+OH-. This study also indicates that
      Cr(III), previously considered as the ultimate kinetically stable species of
      Cr(VI) metabolites, is capable of inducing carcinogenic lesions through
      interaction with a cellular oxygen species.

PMID- 8565118
TI  - Analysis of polychlorinated biphenyl-DNA adducts by 32P-postlabeling.
AB  - Previous studies reported that metabolic activation of certain polychlorinated
      biphenyls (PCBs) resulted in binding to protein, RNA and DNA fractions. However,
      the formation of DNA adducts has not been demonstrated nor have methods been
      optimized for the detection of such adducts. In the present study we investigated
      activation and binding to DNA of lower chlorinated biphenyls using 32P
      postlabeling. The incubation of 2-chloro-, 3-chloro-, 3,4-dichloro- and 3,4,5
      trichlorobiphenyl with calf thymus DNA and liver microsomes from rats treated
      with phenobarbital and 3-methylcholanthrene, followed by oxidation with a
      peroxidase, produced 1-3 major adducts. Reaction of deoxyguanosine 3'
      monophosphate with metabolites of the congeneric chlorinated biphenyls produced
      adducts with similar chromatographic mobility as those with DNA, suggesting that
      guanine was the preferential site of attack. Furthermore butanol and nuclease P1
      enrichments showed different adduct recoveries, depending upon the the
      chlorobiphenyl. Adducts derived from incubations with monochlorobiphenyls were
      recovered 2- to 3-fold higher with butanol, while the recovery of di- and tri
      chlorobiphenyl adducts was 5- to 7-fold higher with nuclease P1. DNA adducts
      formed during the metabolism of 3,4-dichlorobiphenyl were reduced by the sulfur
      nucleophiles, glutathione and N-acetyl-L-cysteine, suggesting that reactive
      semiquinone(s) or quinone(s) are involved. In contrast, the addition of
      superoxide dismutase increased adduct formation, suggesting that the quinone
      metabolites are responsible for the major adducts formed. Our results are
      consistent with the hypothesis that lower chlorinated biphenyls are metabolically
      activated to electrophilic quinoid species which bind to DNA.

PMID- 8565119
TI  - The role of acetylation in the mutagenicity of the antitumor agent, batracylin.
AB  - The role of acetylation in the genotoxicity of the heterocyclic amine,
      batracylin, was evaluated in Salmonella typhimurium strains expressing various
      levels of N- and O-acetyltransferase activity. A significant correlation was
      observed between batracylin-induced mutagenicity and bacterial N
      acetyltransferase activity. Strains with the greatest capacity for N-acetylating
      batracylin (YG 1012 and YG 1024) were the most sensitive to the mutagenic effects
      of the drug. The number of revertants/nmol batracylin and the formation of
      acetylbatracylin were approximately 50-fold greater in YG 1024 compared to TA 98
      which expresses endogenous levels of N-acetyltransferase. A similar response was
      observed with strains YG 1012 and TA 1538. Strains (TA 98/1,8-DNP6 or TA 1538/1,8
      DNP6) which lack the ability to N-acetylate batracylin were the least sensitive
      to the mutagenic effects of the drug. At 1 microgram/plate of batracylin, the
      number of revertants in TA 1538 and TA 98 was 4-fold higher than that observed in
      TA 1538/1,8-DNP6 and TA 98/1,8-DNP6. To determine if batracylin was a substrate
      for human N-acetyltransferases, assays were performed in bacteria expressing NAT1
      or NAT2. Both strains were capable of N-acetylating batracylin. The strain
      expressing NAT2 (DJ 460) formed a significantly greater amount of
      acetylbatracylin, as well as batracylin-induced revertants, compared to the
      strain expressing NAT1 (DJ 400). These results demonstrate that the mutagenicity
      of batracylin is directly related to N-acetyltransferase activity. Data obtained
      in bacteria expressing either human NAT1 and NAT2 show that batracylin is capable
      of being bioactivated by both human enzymes. In addition, the higher enzyme
      activity and mutagenicity in bacteria expressing NAT2 suggests that batracylin is
      a substrate of this enzyme in humans.

PMID- 8565120
TI  - DNA--protein crosslinks, a biomarker of exposure to formaldehyde--in vitro and in
      vivo studies.
AB  - Formaldehyde (FA) is a widely produced industrial chemical. Sufficient evidence
      exists to consider FA as an animal carcinogen. In humans the evidence is not
      conclusive. DNA-protein crosslinks (DPC) may be one of the early lesions in the
      carcinogenesis process in cells following exposures to carcinogens. It has been
      shown in in vitro tests that FA can form DPC. We examined the amount of DPC
      formation in human white blood cells exposed to FA in vitro and in white blood
      cells taken from 12 workers exposed to FA and eight controls. We found a
      significant difference (P = 0.03) in the amount of DPC among exposed (mean +/- SD
      28 +/- 5%, minimum 21%, maximum 38%) than among the unexposed controls (mean +/-
      SD 22 +/- 6%, minimum 16%, maximum 32%). Of the 12 exposed workers, four (33%)
      showed crosslink values above the upper range of controls. We also found a linear
      relationship between years of exposure and the amount of DPC. We conclude that
      our data indicate a possible mechanism of FA carcinogenicity in humans and that
      DPC can be used as a method for biological monitoring of exposure to FA.

PMID- 8565121
TI  - Alterations in expression of CYP1A1 and NADPH-cytochrome P450 reductase during
      lung tumor development in SWR/J mice.
AB  - We investigated the expression of the cytochrome P450 isozyme, CYP1A1, during the
      course of tumor development and examined the distribution of the CYP1A1 protein
      in hyperplastic foci, adenomas and carcinomas. The expression of NADPH-cytochrome
      P450 reductase, a flavoprotein that mediates the reduction of cytochrome P450,
      was also determined. Mice were administered urethane (1 mg/g body wt) and were
      killed at 10, 22 and 52 weeks to coincide with the time at which hyperplastic
      foci, adenomas and carcinomas were established, respectively. Protein
      immunoblotting revealed that the antibody for CYP1A1 detected a protein band of
      approximately M(r) 56,000 in microsomes from mice treated with beta
      naphthoflavone. The antibody for NADPH-cytochrome P450 reductase detected a
      protein band of approximately M(r) 79,000 in microsomes from control mice and
      mice treated with beta-naphthoflavone. Immunohistochemical studies showed that
      CYP1A1 was not detected constitutively in the lungs of both non-tumor- and tumor
      bearing mice. Treatment with beta-naphthoflavone evoked high induction of CYP1A1
      in morphologically normal tissues of all mice, with localization of the protein
      mainly in endothelial and alveolar type II cells. In contrast, inducibility of
      CYP1A1 by beta-naphthoflavone was markedly reduced in early hyperplastic foci
      seen 10 weeks after urethane exposure. At 22 weeks, CYP1A1 was found at low
      levels in both solid and papillary tumors, whereas at 52 weeks, lung carcinomas
      were devoid of expression of this protein. However, CYP1A1 inducibility was
      highly expressed in late hyperplastic foci manifested at 52 weeks. NADPH
      cytochrome P450 reductase was expressed in morphologically normal lung tissue of
      all mice under control conditions and after treatment with beta-naphthoflavone,
      and was localized mainly in Clara and alveolar type II cells. In contrast,
      reductase expression in all tumor sites was diminished and closely paralleled
      that of CYP1A1. These results demonstrated progressive depression of induced
      CYP1A1 and reductase expression in early hyperplasias, adenomas and carcinomas,
      suggesting that the co-ordinate regulation of both enzymes is highly conserved
      during tumor development. Furthermore, these findings suggested diminished
      capabilities for metabolic activation of potential toxicants and/or carcinogens
      after neoplastic transformation.

PMID- 8565122
TI  - Hypochlorous acid/N-chloramines are naturally produced DNA repair inhibitors.
AB  - Human mononuclear leukocytes (HML) respond to oxidative DNA damage by activation
      of ADP ribosylation and initiation of DNA repair synthesis (i.e. unscheduled DNA
      synthesis, UDS), whereas neutrophils do not. When neutrophils are added to HML
      cultures in ratios up to 4:1 ADP ribosylation becomes inhibited to approximately
      50-60%. The ability of neutrophils to inhibit HML ADP ribosylation was shown to
      be dependent on H2O2, chloride ions and myeloperoxidase, which in turn are
      factors known to govern HOCl and N-chloramine production by phagocytic cells.
      HOCl and a model N-chloramine, chloramine T, were shown to give a dose-dependent
      inhibition of DNA repair using four independent estimates, namely ADP
      ribosylation, UDS and the repair of DNA strand breaks estimated by nucleoid
      sedimentation and alkaline elution profiles. All the DNA repair measurements used
      on HML were inhibited approximately 70-80% by 100 microM doses of HOCl or
      chloramine T, which was considered a biologically relevant dose because: (i)
      viable neutrophils equal in concentration to those found in blood could easily
      produce 100 microM levels in short-term culture; (ii) 100 microM doses of these
      agents were not acutely cytotoxic judged by trypan blue stained cells after 30-60
      min exposure and under the conditions used for assay, but yet they abolished 86
      95% of the growth response of HML to phytohemagglutinin.

PMID- 8565124
TI  - p53 mutations in hepatocellular carcinoma related to oral contraceptive use.
AB  - Oral contraceptives (OCs) are implicated in the development of hepatocellular
      carcinoma (HCC). Mitogenic stimulation may be the primary mechanism of
      tumorigenesis, but other factors may also contribute. Mutational spectrum
      analysis can provide insights into pathogenesis, therefore we analyzed the p53
      tumor suppressor gene in 10 HCCs from women with a history of OC use. All were
      non-Asians whose average OC use was 6.7 years (range 2 months-13 years) and whose
      mean age at HCC diagnosis was 48.8 years (range 21-67 years). Each tumor was
      analyzed by immunohistochemistry, DNA sequencing and allelic deletion analysis.
      Three tumors were positive by p53 immunohistochemistry; allelic deletion analysis
      identified loss of heterozygosity in one of four informative cases. Two p53 point
      mutations were found in one tumor containing moderately and well-differentiated
      components; this patient was negative for all serological markers of hepatitis B
      and C infections. Both components showed p53 protein accumulation and a GTTval-
      >GCTala mutation at codon 274. In addition, a silent mutation (ACCthr-->ACTthr)
      at codon 140 of the p53 gene was detected in the moderately differentiated
      component of the tumor. These preliminary data indicate that p53 mutations are
      uncommon in OC-related HCCs. One of the two detected mutations was a G:C-->A:T
      transition at a non-CpG site, which is characteristic of DNA damage by free
      radicals. These data support a model whereby estrogens contribute to HCC
      development primarily through mitogen stimulation and secondarily by mutagenesis
      via hydroxyl radicals produced during estrogen metabolism. Confirmational
      analysis of a larger series is warranted.

PMID- 8565123
TI  - Solution properties and computational analysis of an oligodeoxynucleotide
      containing N-(deoxyguanosin-8-yl)-1-aminopyrene.
AB  - An oligodeoxyribonucleotide 5'-d(CTCATGAPATTCC), in which G(AP) denotes N-(guanin
      8-yl)-1-aminopyrene, the C8-guanine adduct of reductively activated 1
      nitropyrene, was synthesized and characterized by polyacrylamide gel
      electrophoresis, absorption and fluorescence spectroscopy, circular dichroism,
      and thermal melting studies. Polyacrylamide gel electrophoresis showed slower
      mobility of the adducted oligonucleotide in single-stranded form compared to its
      unmodified counterpart, as expected. In duplex form, however (with a
      deoxycytidine opposite the adduct), the adducted 11mer migrated faster than the
      parent duplex. Absorption and fluorescence studies indicated significant
      interaction of the aminopyrene residue with the DNA bases in the modified 11mer.
      The spectroscopic data also suggested the presence of one or more conformers in
      which the aminopyrene residue is quasi-intercalative, as well as one(s) in which
      the aminopyrene is externally bound. Thermodynamic parameters for the helix-to
      coil transitions for the 11mer duplex were determined. The difference in free
      energy (delta delta G degree) between the unmodified and modified sequences was
      relatively small (approximately 1.2 kcal/mol). Circular dichroism spectra
      indicated the presence of essentially B-form DNA. The energy minimizations
      suggested that the most stable conformers shared a common feature: displacement
      of the modified guanine from the double helix. In the global minimum, the
      aminopyrene residue was inserted in the helix in the site of displaced guanine.
      In other low energy structures, the aminopyrene was also displaced towards the
      minor groove (in addition to guanine), or partly inserted and partly in the
      groove. More conventional structures were also encountered, with anti-guanine
      within the helix and aminopyrene in the major groove, or syn-guanine within the
      helix, and aminopyrene in the minor groove. Such structures were 12-20 kcal/mol
      less stable than the global minimum, however. The C8-guanine adduct of
      aminopyrene thus appears to perturb the B-DNA structure to a greater extent than
      do the adducts of less bulky amines such as aminofluorene and 4-aminobiphenyl.

PMID- 8565125
TI  - Detection of DNA adducts in the white blood cells of B6C3F1 mice treated with
      benzene.
AB  - We have employed the P1-enhanced 32P-postlabeling procedure to detect the
      formation DNA of adducts in the white blood cells (WBC) of B6C3F1 mice treated by
      i.p. injection with benzene. Treatment twice a day with 440 mg/kg benzene for 1-7
      days resulted in the formation of one major (adduct 1) and one minor (adduct 2)
      DNA adduct in the WBCs of mice. The same DNA adduct pattern was also found in the
      bone marrow (BM) of benzene treated mice. The relative adduct levels were
      dependent upon both benzene dose from 100-440 mg/kg and treatment time from 1 to
      7 days. The relative adduct levels ranged between 0.11 and 1.33 adducts in 10(7)
      nucleotides for WBCs and 0.16-1.21 adducts in 10(7) nucleotides for BM. Following
      treatment with benzene, the levels of DNA adducts formed in WBCs were
      significantly correlated with the levels of DNA adducts formed in BM (r2 = 0.97,
      P < 0.001). Our results suggest that measurement of DNA adducts in WBCs may be an
      indicator of DNA adduct formation in BM following BZ exposure.

PMID- 8565126
TI  - 1,N6-ethenoadenine and 3,N4-ethenocytosine are excised by separate human DNA
      glycosylases.
AB  - We previously reported our finding that human cells contain glycosylase activity
      toward all four etheno bases formed in DNA by chloroacetaldehyde and related bi
      functional aldehydes. By enzyme purification, including FPLC, we isolated two
      separate glycosylase activities for 1,N6-ethenoadenine (epsilon A) and for 3,N4
      ethenocytosine (epsilon C) respectively, from crude HeLa cell-free extracts,
      which also contained a number of well-described glycosylases. When Mono-S FPLC
      purified proteins were assayed against defined oligomers containing either
      epsilon A or epsilon C, it was found that epsilon A and epsilon C glycosylases
      were completely separated. It could also be demonstrated that each enzyme bound
      to and cut only epsilon A- or epsilon C-containing oligomers respectively. There
      was no overlap in specificity for these two substrates. Several other human
      glycosylase substrates were also tested and none were cleaved by epsilon C
      glycosylase. The epsilon C glycosylase activity identified in the present study
      apparently represents a previously unknown glycosylase. This work also suggests
      that enzyme recognition of closely related DNA adducts may depend upon subtle
      changes in local conformation.

PMID- 8565127
TI  - Inhibition of rat mammary tumorigenesis by dietary cholesterol.
AB  - The effects of dietary cholesterol and oxidized cholesterol on mammary tumor
      development were examined in female Sprague-Dawley rats exposed to the carcinogen
      N-methyl-N-nitrosourea (MNU). Animals were administered 50 mg/kg MNU at 50 days
      of age and fed either a control (AIN-76) diet or the control diet supplemented
      with 0.3% cholesterol or 0.3% oxidized cholesterol for up to 26 weeks. The
      oxidized cholesterol was prepared by heating cholesterol at 110 degrees C for 48
      h. Gas chromatographic analysis of the oxidized cholesterol revealed a 2% yield
      of oxidation products in addition to a large amount of unchanged cholesterol (>
      96%). Tumor incidence in the cholesterol group (67%) was significantly lower than
      in the control group (96%, P < 0.05), but the oxidized cholesterol group (79%)
      was not significantly different from the control or cholesterol groups. Average
      number of tumors per animal was lower in the cholesterol group (1.5) than in the
      control (2.8) or oxidized cholesterol groups (2.3, P < 0.005). Serum low density
      lipoprotein (LDL) cholesterol was greater in the cholesterol (185 +/- 38 mg/dl)
      and the oxidized cholesterol groups (160 +/- 34 mg/dl) than in the controls (55
      +/- 4 mg/dl, P < 0.05), although there was no difference between the cholesterol
      and the oxidized cholesterol groups. These results show that dietary cholesterol
      inhibits mammary tumor development in this model. Elevated serum LDL cholesterol
      may inhibit de novo cholesterol synthesis in preneoplastic and/or tumor cells,
      thereby inhibiting their proliferation.

PMID- 8565128
TI  - Human glutathione S-transferase T1-1 enhances mutagenicity of 1,2-dibromoethane,
      dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium.
AB  - The rat theta class glutathione S-transferase (GST) 5-5 has been shown to affect
      the mutagenicity of halogenated alkanes and epoxides. In Salmonella typhimurium
      TA1535 expressing the rat GST5-5 the number of revertants was increased compared
      to the control strain by CH2Br2, ethylene dibromide (EDB) and 1,2,3,4
      diepoxybutane (BDE); in contrast, mutagenicity of 1,2-epoxy-3-(4'-nitro
      phenoxy)propane (EPNP) was reduced. S.typhimurium TA1535 cells were transformed
      with an expression plasmid carrying the cDNA of the human theta ortholog GST1-1
      either in sense or antisense orientation, the latter being the control. These
      transformed bacteria were utilized for mutagenicity assays. Mutagenicity of EDB,
      BDE, CH2Br2, epibromohydrin and 1,3-dichloroacetone was higher in the
      S.typhimurium TA1535 expressing GSTT1-1 than in the control strain. The
      expression of active enzyme did not affect the mutagenicity of 1,2-epoxy-3-butene
      or propylene oxide. GSTT1-1 expression reduced the mutagenicity of EPNP.
      Glutathione S-transferase 5-5 and GSTT1-1 modulate genotoxicity of several
      industrially important chemicals in the same way. Polymorphism of the GSTT1 locus
      in humans may therefore cause differences in cancer susceptibility between the
      two phenotypes.

PMID- 8565129
TI  - Cyproterone acetate is an integral part of hepatic DNA adducts induced by this
      steroidal drug.
AB  - We have recently shown that cyproterone acetate (CPA), an active component of
      some antiandrogenic drugs, induces the formation of DNA adducts detectable by the
      32P-DNA postlabelling technique in rat liver. The postlabelling technique,
      however, does not provide evidence for the chemical nature of the adducts
      observed. To ascertain whether the CPA-induced adducts do contain CPA, we have
      incubated tritiated CPA with cultured hepatocytes from female rats, digested the
      DNA to 3'-monophosphonucleosides, extracted the DNA adducts formed into butanol
      and phosphorylated the adducts in the extract with unlabelled ATP. One major and
      one minor 3H-labelled adduct spot were detectable on the TLC chromatograms. The
      spots appeared at positions identical to those observed in the 32P-postlabelling
      experiments with unlabelled CPA. Furthermore, the ratio of 3H activity for the
      major versus the minor adduct spot was 11.9 +/- 1.8, which agreed with the
      corresponding ratio for the 32P activities, which was 13.2 +/- 3.5. These
      findings indicate that the CPA-induced DNA adducts, which we have previously
      detected by 32P-postlabelling do contain CPA or CPA metabolites.

PMID- 8565130
TI  - Phenobarbital selectively promotes initiated cells with reduced TGF beta receptor
      levels.
AB  - Phenobarbital (PB) is a potent tumor promoter in rodent liver. In this study we
      investigated whether PB selectively promotes a population of initiated cells with
      reduced levels of transforming growth factor-beta (TGF beta) receptors types I,
      II and III. Liver tumors were induced in male Fischer F344 rats by
      diethylnitrosamine (DEN). Following induction the animals were divided into PB
      treated (DEN/PB) and untreated groups (DEN). After 3 months of treatment half of
      the PB-treated rats were removed from PB for the final month (DEN/PB/OFF). At 4
      months, the livers from rats in the three treatment groups were removed, tumors
      excised and frozen with matched surrounding normal liver tissue. The mRNA levels
      for the TGF beta receptors types I-III were significantly decreased in tumor
      tissue from DEN/PB rats when compared with surrounding normal liver tissue or
      tumors from age-matched untreated controls. In tumors from DEN/PB/OFF rats the
      TGF beta receptor types I-III were also significantly reduced compared with
      controls and not different to tumors from DEN/PB rats. There was no difference in
      the mRNA levels for the TGF beta receptors in tumors from rats exposed to DEN
      alone, when compared with the surrounding normal tissue. These results
      demonstrate that PB selectively promotes initiated cells with reduced levels of
      TGF beta types I-III receptors and suggests a mechanistic role for TGF beta in PB
      induced liver tumor promotion.

PMID- 8565131
TI  - Expression of hepatocyte growth factor and c-met mRNAs during rat chemically
      induced hepatocarcinogenesis.
AB  - The receptor for hepatocyte growth factor (HGF), a potent hepatocyte mitogen, is
      the product of the protooncogene c-met. In order to cast light on their
      significance for hepatocarcinogenesis, levels of both HGF and c-met mRNA were
      evaluated in rat livers during development of 2-acetylaminofluorene (2-AAF)
      selected preneoplastic nodules and carcinomas following diethylnitrosamine (DEN)
      initiation. Rats were given a single i.p. injection of 200 mg/kg body wt DEN and,
      starting 2 weeks later, were administered 0.015% 2-AAF in the diet for up to 6
      weeks. All rats were subjected to partial hepatectomy (PH) at week 3. Additional
      animals undergoing the DEN, 2-AAF and PH regimen were sacrificed at week 40 to
      allow evaluation of carcinomas. Oval cell proliferation, glutathione S
      transferase placental form (GST-P)-positive preneoplastic lesion development and
      HGF and c-met mRNA levels were sequentially analyzed after PH. Numerous oval
      cells were observed 1 week after PH, but were remarkably reduced 2 weeks
      thereafter. The areas of GST-P-positive foci and nodules rapidly increased with
      time not only during 2-AAF feeding, but also to the same degree for at least 2
      weeks after cessation of carcinogenic insult. Dot blot analysis showed HGF
      transcripts to be elevated after PH and during the selective growth conditions of
      2-AAF feeding, dropping after cessation of carcinogenic insult. In the c-met
      transcript case transient increases were observed after PH, followed by a
      decrease. c-met over-expression in nodular livers did not correlate with the
      presence of 2-AAF or lesion development. In most hepatocellular carcinoma samples
      expression of both HGF and c-met mRNAs was below levels in non-neoplastic
      regions. These data suggest that HGF and c-met are directly involved in a
      paracrine growth pathway controlling proliferation in normal hepatocytes and oval
      cells, but not in preneoplastic and neoplastic cells.

PMID- 8565132
TI  - Targeting of O6-methylguanine-DNA methyltransferase (MGMT) activity by
      antimessenger oligonucleotide sensitizes CHO/Mex+ transfected cells to
      mitozolomide.
AB  - The targeting of mRNA with antisense oligonucleotides is increasingly employed to
      inhibit the expression of gene function. Since the level of the DNA repair
      protein O6-methylguanine-DNA methyltransferase (MGMT) is decisive in protection
      of cells against damage produced by alkylating agents, including cytostatic
      drugs, the targeted inhibition of this repair activity might be of importance for
      therapeutic approaches. In order to investigate whether antisense targeted MGMT
      depletion is feasible to transiently modify the sensitivity of cells to
      anticancer drugs, we studied the expression of MGMT and cellular sensitivity upon
      inhibitor and antisense treatment using CHO transfectants expressing human MGMT.
      It was shown by polymerase chain reaction that antisense oligonucleotides
      specifically inhibited MGMT mRNA level. Nevertheless, MGMT protein was found not
      to be reduced significantly, as demonstrated by Western blotting.
      Correspondingly, no significant decrease in MGMT activity was observed, as
      measured 36 h after MGMT antisense oligonucleotide administration. Given together
      with the MGMT depleting agent O6-methylguanine, reduction in MGMT protein as well
      as activity was found. MGMT antisense oligonucleotide enhanced the sensitivity of
      cells to the tumor therapeutic drug mitozolomide, as measured by sister chromatid
      exchange formation. This sensitization was further enhanced by combined treatment
      with antisense oligonucleotide and O6-methylguanine, indicating that MGMT
      antisense can be supportive in sensitization of cells to an alkylating drug.

PMID- 8565133
TI  - The anti-cancer drug camptothecin inhibits elongation but stimulates initiation
      of RNA polymerase II transcription.
AB  - Camptothecin is a widely used anti-tumor drug that specifically inhibits DNA
      topoisomerase I. It is believed that topoisomerase I participates in the process
      of transcription by relaxing torsional stress induced in the duplex DNA by the
      elongating RNA polymerase. We have assessed the effects of camptothecin on RNA
      polymerase II transcription from the dihydrofolate reductase (DHFR) gene in
      Chinese hamster ovary (CHO) cells. Using in vivo [3H]uridine pulse labeling and
      in vitro nuclear run-on techniques to estimate relative rates of transcription,
      it was found that camptothecin stimulated RNA synthesis from promoter-proximal
      sequences of the DHFR gene, while transcription from promoter-distal sequences
      was reduced. Furthermore, camptothecin caused a significant accumulation of RNA
      polymerases in the 5'-end of the DHFR gene. The effect of camptothecin on
      transcription was reversible, resulting in a wave of RNA synthesis recovery in a
      5' to 3' direction through the DHFR gene following a chase with camptothecin-free
      medium. We conclude that camptothecin stimulates initiation but inhibits
      elongation of the RNA polymerase II transcribed DHFR gene.

PMID- 8565134
TI  - Enhancement of thyroid and hepatocarcinogenesis by 1,4-bis[2-(3,5-
      dichloropyridyloxy)]benzene in rats at doses that cause maximal induction of
      CYP2B.
AB  - To investigate the promoting effects of 1,4-bis[2-(3,5-
      dichloropyridyloxy)]benzene (TCPOBOP) on liver and thyroid carcinogenesis of rats
      at doses that cause maximal induction of hepatic CYP2B, 5-week-old male F344 rats
      were given either a single i.p. dose of 75 mg N-nitrosodiethylamine (NDEA)/kg
      body wt in saline or saline alone. After 2 weeks the rats were fed control diet
      or a diet containing 330 or 1000 p.p.m. TCPOBOP or 500 p.p.m. phenobarbital (PB;
      a positive control group). A total of four sequential sacrifices (9, 30, 52 and
      79 weeks of age) was performed. At 30 weeks the mean volume (mm3) of
      hepatocellular foci in NDEA-initiated rats exposed to either dose of TCPOBOP or
      to PB was significantly increased as compared with rats exposed to NDEA followed
      by control diet (P < 0.05). In addition, the volume percentage of liver occupied
      by foci was significantly greater in NDEA-initiated/1000 p.p.m. TCPOBOP-promoted
      rats as compared with rats exposed to NDEA alone (P < 0.05, n = 6). At 52 weeks
      of age the incidences (and multiplicities, in units of tumors per tumor-bearing
      rat) of hepatocellular adenomas were 0, 83 (2.6 +/- 1.3), 100 (3.4 +/- 2.1) or
      67% (2.5 +/- 1.9) in rats exposed to NDEA alone or NDEA followed by 330 or 1000
      p.p.m. TCPOBOP or 500 p.p.m. PB respectively (n = 12). Hepatocellular carcinomas
      were found only in rats given 1000 p.p.m. TCPOBOP (17% incidence) or PB (8%
      incidence) following NDEA initiation. The incidences of thyroid follicular cell
      adenomas were 0, 17, 33 or 8% in rats exposed to NDEA alone or NDEA followed by
      330 or 1000 p.p.m. TCPOBOP or 500 p.p.m. PB respectively. Between 53 and 79 weeks
      of age 38% of rats treated with NDEA alone developed multiple (1.5 +/- 0.8)
      hepatocellular adenomas. This incidence was enhanced to 100% in rats exposed to
      NDEA followed by either 330 or 1000 p.p.m. TCPOBOP. Multiplicities of
      hepatocellular adenomas were also increased significantly (10.5 +/- 3.9, 10.4 +/-
      7.0 and 10.1 +/- 6.7 respectively) in rats promoted with 330 or 1000 p.p.m.
      TCPOBOP or 500 p.p.m. PB. None of the rats exposed to NDEA alone developed
      hepatocellular carcinomas, while multiple hepatocellular carcinomas occurred in
      38% of the rats exposed to 330 p.p.m. and 78% of the rats given 1000 p.p.m.
      TCPOBOP following NDEA initiation. Thyroid follicular cell tumors occurred at 79
      weeks in more than 40 and 50% incidences in rats exposed to NDEA followed by 330
      or 1000 p.p.m. TCPOBOP respectively. Also, a significant decrease in serum levels
      of triiodothyronine and thyroxine were observed in non-initiated 79-week-old rats
      fed 1000 p.p.m. TCPOBOP, compared with age-matched untreated controls (n = 6).
      Increases in hepatic CYP2B-mediated benzyloxyresorufin O-dealkylase activity
      detected in rats exposed to 330 and 1000 p.p.m. TCPOBOP for 2 or 23 weeks were
      similar in magnitude to those caused by 500 p.p.m. PB. Thus TCPOBOP at maximal
      CYP2B induction doses exhibits a strong promoting activity for both liver and
      thyroid of rats.

PMID- 8565135
TI  - Dose-response effects of dietary fiber on NMU-induced mammary tumorigenesis,
      estrogen levels and estrogen excretion in female rats.
AB  - The dose-related effects of the fiber-rich isolate, soft white wheat bran (SWWB),
      and the pure fiber, cellulose, on N-nitrosomethylurea (NMU)-induced mammary
      tumorigenesis was assessed in F344 female rats. SWWB (45% total dietary fiber,
      TDF) was added to the AIN-76A high-fat diet at 9, 12, 15 and 18%; cellulose (98%
      TDF) was added to the same diet at 4.5, 6, 7.5 and 9%, to give equivalent amounts
      of TDF. The experimental diets were fed 3 days post-NMU and continued for a
      period of 25 weeks, at which time the experiment was terminated and tumors
      enumerated. It was found that significant inhibition of mammary carcinoma
      occurred only at 9% SWWB, non-significant inhibition occurred at 12% SWWB, and no
      inhibition was seen at higher doses. Cellulose-fed animals exhibited consistently
      higher tumor yields regardless of dose. The difference in tumor yields between
      the 9% SWWB group and the remaining seven groups was attributable to an increased
      incidence in tumors characterized histologically as intraductal proliferation and
      ductal carcinoma in situ in the latter. Analysis of blood, urine and fecal
      estrogens was conducted to test whether dietary fiber exerted its tumor
      inhibiting effect by altering the enterohepatic recycling of estrogens. Although
      SWWB, in general, lowered urinary estrogen excretion, increased fecal estrogen
      excretion and lowered blood estrogens, there was no consistent correlation
      between the amount of SWWB consumed, estrogen status and tumor yields. These
      results suggest that (i) wheat bran fiber at 9%, or minor constituents associated
      with it, contain anti-promoting properties that cellulose lacks; (ii) SWWB
      appears to exert its effects by suppressing the clonal expansion phase of mammary
      carcinogenesis; (iii) there is an upper limit (12-15% w/w) to the protective
      effects of SWWB; and (iv) the effects of SWWB on mammary tumorigenesis may not be
      attributed to alterations in the enterohepatic recycling of estrogens.

PMID- 8565136
TI  - Biological consequences of DNA damage introduced in bacteriophage PM2 DNA by
      hydrogen peroxide-mediated free radical reactions.
AB  - In order to study the biological consequences of DNA damage induced by H2O2
      mediated free radical reactions, DNA from bacteriophage PM2 was exposed to H2O2,
      Fe(3+)-citrate and ascorbate either alone or in combination. Induction of DNA
      lesions was determined as well as the biological activity of the phage DNA.
      Exposure to H2O2 alone resulted in max. 0.2 single-strand breaks per molecule; in
      the presence of Fe(3+)-citrate, the yield was approximately 4-fold higher. Under
      both conditions no double-strand breaks could be detected and the biological
      activity was not diminished. This indicates that low levels of single-strand
      breaks as generated by H2O2/Fe(3+)-citrate do not inactivate PM2 DNA. Exposure to
      ascorbate in the presence Fe(3+)-citrate resulted in extensive induction of
      single-strand breaks. However, at ascorbate concentration where approximately 3
      single-strand breaks per molecule were induced, again no double-strand breaks
      could be detected and the biological activity of the DNA was not diminished. At 5
      mM ascorbate, single-strand breaks were above the detection limit. Under these
      conditions, 0.02 double-strand breaks were induced and the biological activity
      was reduced to 50%. The contribution of double-strand breaks to biological
      inactivation was calculated to be approximately 3%. When PM2 DNA was exposed to
      H2O2 in the presence of ascorbate/Fe(3+)-citrate, a typical biphasic dose-effect
      relationship was observed both for the induction of double-strand breaks and
      biological inactivation, suggesting that one or more reactive species sensitive
      to H2O2 play a critical role. The .OH scavenger t-butanol appeared to be
      relatively inefficient in protecting PM2 DNA, which may indicate that other
      reactive species than .OH are involved. Our data suggest that other reactive
      species than .OH, such as the ferryl ion, are involved in H2O2-mediated DNA
      damage induction and biological inactivation.

PMID- 8565137
TI  - Formation and persistence of DNA adducts in different target tissues of rats
      after multiple administration of benzo[a]pyrene.
AB  - Exposure of humans to polycyclic aromatic hydrocarbons is an ongoing concern
      because of the carcinogenicity of these substances. DNA adducts are being
      increasingly used as indicators of carcinogen exposure. While considerable
      experimental evidence exists to support their use there are aspects that require
      further attention, especially after repeated exposure, which has led to this
      series of experiments. Male Sprague-Dawley rats were dosed with 10 mg/kg
      benzo[a]pyrene (B[a]P) i.p., 3 times/week for 2 weeks. At 1, 3, 7, 14, 28 and 56
      days after the last treatment liver, lung, spleen and peripheral blood
      mononuclear cells (PBMNs) were sampled. The DNA adduct levels, as measured by the
      32P-postlabelling technique, were significantly increased in all tissues, with
      lung having the highest levels. At day 14 total DNA adducts in lung, spleen and
      PBMNs were still > 50% of the level at day 1. The removal of total DNA adducts
      was found to be fastest in liver > spleen > PBMNs > lung. A consistent
      correlation of total adducts between the lung and PBMNs was observed. A major
      adduct, designated adduct 1, was detected in all tissues, while adduct 4 was only
      found in liver and lung. Adduct 5 was detected only in lung, where it constituted
      approximately 38-49% of total adducts and persisted at a higher level than either
      adduct 1 or adduct 4 for the entire post-exposure period. These results indicate
      that B[a]P induced a significant increase in DNA adduct levels in all tissues
      tested and that total adducts in PBMNs reflect total lung adduct levels. DNA
      adducts were still readily detectable 56 days after exposure ceased. Thus the
      results support the use of PBMNs as surrogates for estimation of B[a]P exposure
      in lung, the primary target organ, and indicate that samples taken days or weeks
      after repeated exposure will still yield DNA adducts at detectable levels. The
      role and significance of adduct 5 deserves further investigation, as it was
      detected only in the primary target organ for B[a]P-induced cancer.

PMID- 8565138
TI  - Seasonal variation of DNA adduct pattern in human lymphocytes analyzed by 32P
      HPLC.
AB  - 32P-HPLC is a recently published method to generate DNA adduct profiles after
      exposure to a complex of genotoxic substances. The low detection limit enables
      characterization of individual DNA adducts in the general population. The 32P
      HPLC method was applied to human lymphocytes and granulocytes from Silesia, a
      polluted industrial region in the south of Poland. Human samples were collected
      at the end of winter and summer to investigate the seasonal influence on DNA
      adduct formation. In lymphocytes a strong seasonal variation was seen in total
      DNA adducts, with winter values exceeding the summer values by 7.33 +/- 3.56
      times. Granulocytes did not show any seasonal variation. In winter-collected
      lymphocytes the DNA adduct levels were 21.4 +/- 16.6/10(8) normal nucleotides
      (NN) while the summer values were 2.96 +/- 2.46/10(8) NN. Granulocytes had 8.06
      +/- 7.76 and 9.59 +/- 6.19 DNA adducts/10(8) NN during winter and summer
      respectively. The lymphocyte DNA adduct profile consisted of at least 16
      individual or clusters of DNA adducts. All 16 had a clear winter influence, with
      a winter:summer ratio of 1.6-15.3, indicating exposure to a complex mixture of
      genotoxic substances. The DNA adducts analyzed in human lymphocytes had retention
      times similar to DNA adducts generated by polycyclic aromatic hydrocarbons. The
      suggested candidates for DNA adducts displayed a similar seasonal variation in
      airborne particles to that found in DNA adducts in lymphocytes of humans living
      in the area. This is the first application of the 32P-HPLC method to analysis of
      DNA adducts in human tissues.

PMID- 8565139
TI  - Validation in rats of two biomarkers of exposure to the food-borne carcinogen 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP): PhIP-DNA adducts and
      urinary PhIP.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts in white blood
      cells and tissues and unmetabolized PhIP in urine were validated as biomarkers of
      exposure in male Fischer-344 rats treated with daily PhIP doses ranging from 1 to
      0.0001 mg/kg. At the end of the 23 day treatment period all rats were killed and
      their blood and 10 tissues were collected for isolation of DNA and analysis of
      PhIP-DNA adducts by 32P-postlabeling and alkaline hydrolysis with GC/MS. PhIP-DNA
      adducts could be detected only in animals receiving 1 or 0.1 mg/kg/day, with
      highest adduct levels in the pancreas, heart and kidneys. There was a good
      correlation (r = 0.77, P < 0.005) between the two methods of analysis, with
      average adduct levels determined by 32P-postlabeling approximately 1.4 times
      higher than those determined by alkaline hydrolysis with GC/MS. PhIP-DNA adducts
      accumulated in most tissues, especially in the liver, kidneys, heart and
      pancreas, with lower levels in the white blood cells, small intestine, stomach,
      colon and cecum. Using GC/MS levels of unmetabolized PhIP were measurable in four
      weekly 24 h urine samples even at 0.0001 mg/kg/day, a dose comparable with
      reported human dietary exposure. A linear dose-response was obtained for
      excretion of unmetabolized PhIP across the range of doses, with approximately
      1.8% of the dose excreted daily, largely independent of the number of doses. No
      PhIP was detected in the urine of untreated rats. If it can be shown that a
      constant percentage of PhIP is excreted unchanged in human urine, irrespective of
      dose, as has been found with the rat, measurement of urinary PhIP could be used
      as an accurate measure of dietary exposure to this amine in man.

PMID- 8565140
TI  - Inhibition of UV light- and Fenton reaction-induced oxidative DNA damage by the
      soybean isoflavone genistein.
AB  - We have investigated the effect of the soybean isoflavone genistein on 8-hydroxy
      2'-deoxyguanosine (8-OHdG) formation in calf thymus DNA exposed to either UV
      irradiation or the Fenton reaction system. Under the conditions used we observed
      that UV light and the Fenton reaction significantly increase 8-OHdG formation in
      DNA. Co-incubation with genistein inhibits the formation of 8-OHdG induced by
      either UV light irradiation or the Fenton reaction in a dose-dependent manner.
      The quenching effect of genistein on 8-OHdG formation induced by UV light is much
      more potent than that by the Fenton reaction, suggesting that the mechanisms of 8
      OHdG formation may differ between the two systems. We further compared the
      antioxidant activities and quenching effect on 8-OHdG formation of genistein with
      biochanin A. Genistein potently scavenges both hydrogen peroxide in the medium
      and superoxide anion generated by xanthine/xanthine oxidase, whereas biochanin A
      has either a weak or no scavenging effect on these reactive oxygen species.
      However, both genistein and biochanin A display a similar quenching effect on UV
      light-induced 8-OHdG formation. These results suggest that the quenching effect
      of genistein and biochanin A on UV light-induced 8-OHdG formation is different
      from their ability to scavenge hydrogen peroxide and superoxide anion. The potent
      inhibition of UV light-induced oxidative DNA damage by genistein suggests its
      potential anticarcinogenic role in photocarcinogenesis.

PMID- 8565141
TI  - The model Ah-receptor agonist beta-naphthoflavone inhibits aflatoxin B1-DNA
      binding in vivo in rainbow trout at dietary levels that do not induce CYP1A
      enzymes.
AB  - beta-Naphthoflavone (BNF), a well-known Ah-receptor agonist, has been believed to
      inhibit aflatoxin B1 (AFB1) carcinogenesis in rats and rainbow trout primarily
      through induction of the cytochrome P450 1A (CYP1A) enzyme subfamily and
      consequent diversion of AFB1 to the less carcinogenic phase I metabolite
      aflatoxin M1 (AFM1). This study investigates the dose responsive effects of
      dietary BNF treatment on CYP1A induction. AFM1 formation, AFB1-8,9-epoxide
      formation and AFB1-DNA binding in the trout model. Pre-feeding diet containing 10
      200 p.p.m. BNF after AFB1 i.p. injection provided dose-dependent induction of
      CYP1A-dependent ethoxyresorufin-O-deethylase (EROD) activity and inhibition of in
      vivo AFB1-DNA binding. However, most of the observable inhibition of DNA
      adduction (45% inhibition) had occurred at 10 p.p.m. BNF without detectable EROD
      induction; higher doses of BNF up to 200 p.p.m. induced EROD > 6-fold but
      provided only another 15% inhibition of DNA adduction in vivo. When in vitro AFB1
      DNA binding was assessed using liver microsomes from trout fed 10-100 p.p.m. BNF,
      induced microsomal EROD activity correlated moderately with reduction of in vitro
      AFB1-DNA binding activity. However, BNF treatment in a low dose range (0.2-10
      p.p.m.) also strongly inhibited in vivo hepatic AFB1-DNA binding (69% inhibition
      at 5 p.p.m. BNF in this experiment), in a dose-dependent manner, in the complete
      absence of detectable EROD induction. The microsomes from 5 p.p.m. BNF-treated
      trout had no more EROD activity than control microsomes, and no less capacity for
      catalyzing AFB1-DNA binding in vitro than control microsomes. Thus, the potent
      inhibition of hepatic AFB1-DNA binding in vivo by 5 p.p.m. BNF was a result of
      neither CYP1A enzyme induction nor irreversibly reduced catalytic capacity for
      AFB1-8,9-epoxide formation. Direct analysis of AFB1 metabolites formed in vitro
      by liver microsomes from trout fed 10, 100 and 500 p.p.m. BNF showed that low
      dietary BNF (10 p.p.m.) neither induced microsomal CYP1A-mediated AFM1 formation
      nor altered AFB1-8,9-epoxide formation compared to the control. By comparison,
      100 and 500 p.p.m. BNF pretreatment significantly elevated microsome-catalyzed
      AFM1 formation in vitro (P < 0.001), and this increase was highly correlated with
      increased EROD activity (r2 = 0.999, P < 0.001). Upon in vitro addition, BNF was
      found to be a potent inhibitor of microsome-mediated AFB1-8,9-exo-epoxide
      formation (IC50 = 2.6 +/- 0.1 microM) and AFB1-DNA binding (inhibition constant
      Ki = 3.03 +/- 0.25 microM). These findings indicate that CYP1A enzyme induction
      can contribute modestly to BNF protection against AFB1 in this species both in
      vivo and in vitro at higher BNF doses, but does not do so at lower doses.
      Instead, enzyme inhibition by BNF against AFB1 8,9-epoxidation appears to be the
      predominant protective mechanism at higher BNF doses, and the sole protective
      mechanism at low doses, in the rainbow trout. These findings demonstrate that
      mechanisms of chemoprevention can change with anticarcinogen dose, and caution
      that even potent induction of phase I or phase II activities does not assure that
      pathway to be a predominant protective mechanism in vivo.

PMID- 8565142
TI  - Activation of tamoxifen and its metabolite alpha-hydroxytamoxifen to DNA-binding
      products: comparisons between human, rat and mouse hepatocytes.
AB  - The metabolic activation of tamoxifen and its metabolite alpha-hydroxytamoxifen
      in primary cultures of rat, mouse and human hepatocytes has been compared. The
      extent of formation of DNA adducts in these cells was measured by 32P
      postlabelling, using either nuclease P1 digestion or sorbent extraction of DNA
      digests to enhance the sensitivity of the assay. DNA adducts were readily
      detected in rat hepatocytes treated with 1 or 10 microM tamoxifen (mean levels
      18.2 and 89.8 adducts/10(8) nucleotides respectively). Similar levels of adducts
      were formed by mouse hepatocytes (15.0 +/- 1.8 adducts/10(8) nucleotides, 10
      microM tamoxifen). However DNA adducts were not detected in tamoxifen-treated
      human hepatocytes with a detection limit for the assay of 4 adducts/10(10)
      nucleotides. Treatment of rat cells with alpha-hydroxytamoxifen resulted in 15-
      to 63-fold higher levels of adducts than with comparable concentrations of
      tamoxifen. A similar level of adducts was also seen in mouse hepatocytes treated
      with alpha-hydroxytamoxifen at the 1 microM concentration (173.9 +/- 4.1
      adducts/10(8) nucleotides). Treatment of human cells with alpha-hydroxytamoxifen
      resulted in DNA adduct formation at levels (1.94 +/- 0.89 and 18.9 +/- 17.9
      adducts/10(8) nucleotides at 1 and 10 microM respectively) approximately 300-fold
      lower than those in rat hepatocytes. The presence of alpha-hydroxytamoxifen in
      the culture medium from experiments where cells were incubated with tamoxifen was
      monitored by mass spectrometry. Concentrations were found to be approximately 50
      fold lower in the medium from human hepatocytes than from rat and mouse
      hepatocytes.

PMID- 8565143
TI  - DNA adduct formation, cell proliferation and aberrant crypt focus formation
      induced by PhIP in male and female rat colon with relevance to carcinogenesis.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces colon tumors in
      male, but not female, F344 rats. We investigated the mechanisms leading to this
      difference by measuring the level of PhIP-DNA adducts, the enhancement of cell
      proliferation and aberrant crypt focus (ACF) formation in colon mucosa. PhIP was
      administered in the diet at a level of 0.04% to both male and female F344 rats
      for 1-8 weeks. The level of DNA adducts in the colon mucosa was measured using
      the 32P-postlabeling method. Four major PhIP-DNA adducts were detected in fairly
      constant proportions in all the animals examined. The level of PhIP-DNA adducts
      in male and female rats was the same, indicating no direct correlation between
      adduct levels and carcinogenesis. Labeling indices (LIs) were determined by
      measuring BrdU incorporation in rats after feeding with a PhIP diet for 4, 8 and
      12 weeks. After 8 weeks administration the LI had increased 1.5-fold in the colon
      of the male rats, but no increase was observed in the female rats. ACF formation
      was examined after feeding with a PhIP diet for 14 weeks. The number of aberrant
      crypt foci was 6.6 +/- 1.5 per rat in males and 1.9 +/- 0.5 per rat in females.
      Thus differences in colon tumor development in male and female rats takes place
      at an early stage(s). Our results suggest that, in addition to DNA adduct
      formation, enhanced proliferation contributes to the formation of ACFs, which are
      premalignant lesions of the colon.

PMID- 8565144
TI  - Cytogenetic effects of occupational exposure in the peripheral blood lymphocytes
      of pesticide sprayers.
AB  - The potential clastogenic effect of pesticides was investigated in 56 (29 indoor
      and 27 outdoor) agricultural workers exposed to complex chemical mixtures.
      Exposed and referent subjects were selected from the same geographical area
      located in Ionia, province of Thessaloniki, Greece. Chromosome aberrations (CA)
      and sister chromatid exchanges (SCE), were studied in peripheral lymphocytes.
      Comparison between workers and control group revealed that the individuals
      exposed to pesticides showed substantial clastogenic effects (CA = 2.66% compared
      to 0.53%, P < 0.001), in their lymphocytes without indication of increases in
      their basal frequency of SCE. Moreover, the condition of exposure has been found
      to influence the CA frequency. It was observed that individuals working
      exclusively in greenhouses (confined spaces) showed higher CA levels than
      subjects working in open fields (3.37 versus 1.88, P < 0.01). No significant
      difference in their expression of CA between smokers and non-smokers was found.
      The present chromosome study included workers living in the close vicinity of a
      large industrial zone near Thessaloniki. The percentage of CA in these indoor
      sprayers was higher compared to our previous study carried out in a different
      area of Thessaloniki, free of industrial plants (3.37% compared to 2.14%, P <
      0.02).

PMID- 8565145
TI  - Glucocorticoid-induced changes in liver: inhibition of nuclear Ca2+, Mg(2+)
      dependent endonuclease activity in response to dexamethasone administration.
AB  - The endogenous Ca2+, Mg(2+)-dependent endonuclease activity in nuclei from livers
      of rats receiving daily injections of the synthetic glucocorticoid dexamethasone
      was examined with respect to the production of both single and double strand
      breaks in chromatin DNA. The ability to form single strand breaks was measured by
      means of a nick translation assay and double strand breaks by following the
      appearance of nucleosomal ladders. A fall in the activity causing double strand
      breaks to approximately 50 per cent of the control value was apparent at 12 h
      after the first injection of the steroid. A fall of 25-30 per cent was also
      observed in the nicking activity but this was not apparent until 24 h after the
      first steroid injection. Both endonuclease activities remained at these lower
      levels for the remainder of the period of treatment. Nuclear extracts from
      dexamethasone-treated rats also showed a reduced ability to produce nucleosomal
      ladders when incubated with rat muscle nuclei, indicating that the inhibition
      observed in intact nuclei from treated animals was independent of any changes in
      chromatin structure. On the other hand the nick translation activity of the two
      extracts was the same when calf thymus DNA was used as the substrate suggesting
      that steroid-induced alterations in chromatin structure may be a critical factor
      in the reduced level of this activity observed in intact nuclei.

PMID- 8565146
TI  - Enzymatic, biophysical and ultrastructural changes of plasma membranes in
      chemical-induced rat hepatoma.
AB  - Plasma membranes from liver of control rats or from chemical-induced hepatoma
      were prepared. The basal activity of adenylate cyclase was increased
      significantly in the rat plasma membranes of DEN-induced hepatoma compared to
      normal tissue. The glucagon-induced response on the cellular effector systems via
      guanine nucleotide-binding regulatory proteins (G proteins) was inhibited in
      hepatoma plasma membranes. These findings suggest that in hepatoma membranes,
      unlike normal hepatic membranes, the response to hormonal stimuli through
      regulatory G proteins results in a loss of response to glucagon, as well as to
      GTP plus glucagon or to GTP gamma S. However, the activating effects of
      forskolin, which catalyses the formation of cyclic AMP from ATP acting on the
      catalytic subunit, were to some extent retained. The methyltransferase-I behaved
      in the opposite direction to the adenylate cyclase, showing a decreased activity
      in hepatoma plasma membranes compared to control membranes. In contrast, the
      activity of the ecto-5'-nucleotidase was significantly increased in hepatoma.
      These enzymatic changes have been found to influence the membrane fluidity and to
      be responsible for the ultrastructural modifications of hepatoma plasma membranes
      which are induced by chemical carcinogens.

PMID- 8565147
TI  - Citrinin affects the oxidative metabolism of BHK-21 cells.
AB  - The effects of citrinin on energy production along the respiratory chain and on
      glycolytic lactate production were examined in BHK-21 cultured cells. Citrinin
      inhibited the oxygen consumption rate by about 45 per cent. The respiratory rate
      of digitonin-treated cells energized with succinate, in the presence of ADP, was
      reduced by about 39 per cent. The mycotoxin inhibited the glucose utilization of
      BHK-21 cells by about 86 per cent. Cells treated with citrinin produced a small
      quantity of pyruvate, but were unable to produce lactate. It is concluded that
      BHK-21 cells cannot generate lactate when oxidative metabolism is inhibited by
      citrinin. The perturbations in BHK-21 cells caused by citrinin are due to
      alterations in mitochondrial function and in the glycolytic anaerobic pathway.

PMID- 8565148
TI  - Lovastatin induces differentiation of Mono Mac 6 cells.
AB  - The proliferation of human monocytic Mono Mac 6 cells was significantly retarded
      by treatment with lovastatin (LOV, 10 microM) for 72 h. Treatment of Mono Mac 6
      cells with LOV increased surface protein expression of monocyte-associated CD14
      and the integrin-chain CD11b towards levels found in isolated human blood
      monocytes. These effects were dose-dependent and completely reversed by the
      isoprenoid precursor mevalonate (MVA). LOV failed to induce growth retardation
      and upregulation of CD11b or CD14 in the less mature premonocytic U937 cell line.
      While CD11b expression was comparable in Mono Mac 6 cells treated with LOV (10
      microM), TNF (100 U ml-1) or LPS (10 ng ml-1), upregulation of CD14 by LOV was
      less pronounced. Basal CD23 expression was unaffected by LOV but markedly reduced
      by treatment with TNF or LPS. Moreover, LOV enhanced Mono Mac 6 adhesiveness to
      human umbilical vein endothelial cells to levels found in isolated human blood
      monocytes, probably due to the increased CD11b and CD14 expression. In
      conclusion, LOV can induce differentiation of monocytic cells which is reflected
      by the retardation of growth, expression of CD14 and CD11b, and enhanced
      adhesiveness.

PMID- 8565149
TI  - Release of arachidonic acid via Ca2+ increase stimulated by
      pyrophosphonucleotides and bradykinin in mammary tumour cells.
AB  - The relationship between the increase of intracellular Ca2+ and the release of
      arachidonic acid by bradykinin and pyrophosphonucleotides was studied in cultured
      mammary tumour cells, MMT060562. Bradykinin, ATP, UTP and UDP induced an increase
      of intracellular Ca2+ and the release of arachidonic acid from phospholipids into
      the extracellular fluid. Release of arachidonic acid was also induced by the
      application of the Ca2+ ionophore, A23187. Liberation of arachidonic acid by
      bradykinin and ATP was reduced by mepacrine, a blocker of phospholipase A2 and W
      7, a calmodulin antagonist. It is suggested that the increase in cytosolic Ca(2+)
      induced release of arachidonic acid occurs through activation of calmodulin
      dependent phospholipase A2.

PMID- 8565150
TI  - Microdensitometric measures of cytoplasmic RNA and total protein in pyramidal
      neurons of the insular cortex and midfrontal gyrus in patients with Alzheimer's
      disease.
AB  - Scanning and integrating microdensitometry of azure B- and Coomassie brilliant
      blue G-stained tissue sections was used to measure the levels of RNA and protein,
      respectively, in pyramidal neurons of the insular cortex (INS) and midfrontal
      gyrus (MFG) in patients with Alzheimer's disease (AD) and age-matched,
      nondemented control subjects. AD was associated with a decreased neuronal RNA (by
      7.4 per cent) and protein (by 28.7 per cent) content in INS. Although the
      neuronal RNA content was maintained at the control amounts in MFG, the average
      protein level was lower (14.7 per cent) in AD patients. These results demonstrate
      a disease-related impairment in metabolic function in two brain regions connected
      via discrete corticocortical pathways. Such findings support the hypothesis that
      a primary site of pathology occurs in AD, and specific neural deficits occur
      secondarily in certain connected brain regions.

PMID- 8565151
TI  - Increase of cyclin B by overexpression of cystatin alpha.
AB  - Degradation of cyclin B was effectively suppressed when cells were treated with
      ALLN (N-acetylleucylleucylnorleucinal) which inhibits proteasome, calpain and
      cysteine proteinase cathepsins. In order to examine which protease degrades
      cyclin B, the effect of a cathepsin inhibitor, cystatin alpha, was investigated.
      The cystatin alpha gene was inserted into an inducible expression vector, pMSG,
      and transfected into NIH3T3 mouse fibroblasts. The expression of cystatin alpha
      was induced effectively in the transfected cells after treatment with
      dexamethasone. Overexpression of cystatin alpha resulted in an increase of the
      amount of cyclin B, suggesting that cysteine proteinase cathepsins might be
      involved in the degradation of cyclin B.

PMID- 8565152
TI  - Muscle glucose 6-phosphate dehydrogenase (G6PD) deficiency and oxidant stress
      during physical exercise.

PMID- 8565153
TI  - Second European Stroke Prevention Study.

PMID- 8565154
TI  - Dressing up the Palmaz-Schatz stent.

PMID- 8565155
TI  - Operator-specific outcomes. A call to professional responsibility.

PMID- 8565156
TI  - Extracellular potassium modulation of drug block of IKr. Implications for torsade
      de pointes and reverse use-dependence.
AB  - BACKGROUND: Torsade de pointes often occurs with underlying hypokalemia and
      bradycardia. A common effect of many drugs producing torsade de pointes is block
      of the rapidly activating component of the cardiac delayed rectifier (IKr). In
      this study, we evaluated the effect of changing extracellular potassium ([K+]o)
      on IKr block by the nonspecific agent quinidine and by the specific IKr blocker
      dofetilide. METHODS AND RESULTS: IKr was measured in AT-1 cells, where
      contaminating outward currents are absent. The drug concentration producing 50%
      inhibition of IKr tails (IC50) was strikingly [K+]o-dependent. Elevating [K+]o
      from 1 to 8 mmol/L increased the IC50 for dofetilide block from 2.7 +/- 0.9 to 79
      +/- 32 nmol/L and for quinidine block from 0.4 +/- 0.1 to 3.8 +/- 1.2 mumol/L.
      CONCLUSIONS: (1) The increase in drug block with low [K+]o provides a mechanism
      to explain the link between hypokalemia and torsade de pointes. (2) Elevations in
      [K+]o occur with myocardial ischemia and with rapid pacing. Possible consequences
      of blunted drug block with high [K+]o include loss of drug efficacy with ischemia
      and with rapid pacing; the latter may contribute to "reverse use-dependent"
      action potential prolongation. Extracellular potassium is a critical determinant
      of drug block of IKr, with substantial clinical implications.

PMID- 8565157
TI  - Heparin-coated Palmaz-Schatz stents in human coronary arteries. Early outcome of
      the Benestent-II Pilot Study.
AB  - BACKGROUND: The purpose of the Benestent-II Pilot Study was to evaluate the
      safety of delaying and eliminating anticoagulant therapy in patients receiving a
      heparin-coated stent in conjunction with antiplatelet drugs. METHODS AND RESULTS:
      The study consisted of three initial phases (I, II, III) during which resumption
      of heparin therapy after sheath removal was progressively deferred by 6, 12, and
      36 hours. In phase IV, coumadin and heparin were replaced by 250 mg ticlopidine
      and 100 mg aspirin. Of the 207 patients with stable angina pectoris and a de novo
      lesion in whom heparin-coated stent implantation was attempted, implantation was
      successful in 202 patients (98%). Stent thrombosis did not occur during all four
      phases, and the overall clinical success rate at discharge was 99%. Bleeding
      complications requiring blood transfusion or surgery fell from 7.9% in phase I to
      5.9%, 4%, and 0% in the three following phases. Hospital stay was 7.4, 6.1, 7.2,
      and 3.1 days for the consecutive phases. The restenosis rate for the combined
      four phases was 13% (15% in phase I, 20% in phase II, 11% in phase III, and 6% in
      phase IV). The overall rate of reintervention for the four phases was 8.9%. At 6
      months, 84%, 75%, 94%, and 92% of the patients of phases I to IV, respectively,
      were event free. For the four phases, the event-free rate was 86%, which compares
      favorably with the rate observed in the Benestent-I study (80%; relative risk,
      0.68 [0.45 to 1.04]). CONCLUSIONS: The implantation of stents coated with
      polyamine and end-point-attached heparin in stable patients with one significant
      de novo coronary lesion is well tolerated, is associated with no (sub)acute stent
      thrombosis, and results in a favorable event-free survival after 6 months.

PMID- 8565158
TI  - Reduction in thrombotic events with heparin-coated Palmaz-Schatz stents in normal
      porcine coronary arteries.
AB  - BACKGROUND: The use of stents improves the result after balloon coronary
      angioplasty. Thrombogenicity of stents is, however, a concern. In the present
      study, we compared stents with an antithrombotic coating with regular stents.
      METHODS AND RESULTS: Regular stents were placed in coronary arteries of pigs
      receiving no aspirin (group 1; n = 8) or aspirin over 4 weeks (group 2, n = 10)
      or 12 weeks (group 3, n = 9). Stents coated with heparin (antithrombin III
      uptake, 5 pmol/stent) were placed in 7 pigs that did not receive aspirin (group
      4). The other animals received aspirin and coated stents with a heparin activity
      of 12 pmol antithrombin III/stent (group 5, n = 10) or 20 pmol/stent (group 6, n
      = 10; group 7, n = 10). Quantitative arteriography was performed at implantation
      and after 4 (groups 1, 2, and 4 through 6) or 12 weeks (groups 3 and 7). In an
      additional 5 animals, five regular and five coated stents (20 pmol/stent) were
      placed and explanted after 5 days for examination of the early responses to the
      implants. Thrombotic occlusion of the regular stent occurred in 9 of 27 in groups
      1 through 3. However, in 0 of 30 of the animals receiving high-activity heparin
      coated stents (groups 5 through 7), thrombotic stent occlusion was observed (P <
      .001). Histological analysis at 4 weeks showed that the neointima in group 6 was
      thicker compared with its control group 2 (259 +/- 104 and 117 +/- 36 microns, P
      < .01), but at 12 weeks the thickness was similar (152 +/- 61 and 198 +/- 49
      microns, respectively). Comparison at 5 days suggested delayed endothelialization
      of the coating. CONCLUSIONS: High-activity heparin coating of stents eliminates
      subacute thrombosis in porcine coronary arteries.

PMID- 8565159
TI  - Analysis and comparison of operator-specific outcomes in interventional
      cardiology. From a multicenter database of 4860 quality-controlled procedures.
AB  - BACKGROUND: Medical consumers are increasingly requesting methods to discriminate
      among the results of different providers. Standards for appropriate modeling,
      risk adjustment, and evaluation ("scorecarding") in this setting are not well
      developed, although such evaluation is being performed by the medical insurance
      industry and by several states in the United States. Our objectives were to
      develop and examine clinically meaningful methodology for assessing the operator
      specific results for percutaneous coronary revascularization. METHODS AND
      RESULTS: From a multicenter database of patients treated since January 1, 1990,
      we used training and validation samples (n = 4860) to develop several models for
      risk adjustment and applied them to 38 providers performing 25 to 523 procedures
      in the database. Models were developed using multivariable logistic regression
      techniques for combinations of the end points of death, myocardial infarction,
      bypass surgery, and procedural success. Models were evaluated for predictive
      accuracy by using receiver operating characteristic (ROC) analysis, for the
      capacity to discriminate between superior and inferior provider outcomes, and for
      subjectivity and concordance. Major complications occurred in 3.6% of patients.
      The area under the ROC curve (with perfect discriminatory accuracy, area = 1.0;
      with no apparent accuracy, area = 0.5) in the validation sample, and frequency of
      identification of operators with outcomes outside the 95% CI for the outcome in
      question for the models were for death, 0.85 and 7.9%; for death, Q-wave
      infarction, and bypass surgery, 0.77 and 13.2%; for death, all infarction, and
      bypass surgery, 0.66 and 10.5%; and for procedural success, 0.76 and 23.7%. For
      the models as a group, identification of outliers was inversely related to
      provider volume (P = .05). Models evaluating non-Q-wave infarction or requiring
      measurement of percent diameter stenosis were identified as being most
      susceptible to provider manipulation. CONCLUSIONS: For percutaneous coronary
      revascularization, modeling to discriminate between provider outcomes is limited
      by the low incidence of major adverse events, subjectivity or susceptibility to
      manipulation of more frequently occurring adverse events, the generally modest
      predictive capacity of the models, and the low volume of individual provider
      treatments. Modeling will be most useful in the identification of providers with
      extremely poor outcomes and for discrimination between providers with very large
      procedural volume. Until improved understanding of the biological and mechanical
      correlates of major complications allows the development of more predictive
      models, interpretation of the results of scorecarding, particularly for low
      volume providers, should be made with caution.

PMID- 8565160
TI  - Beta fibrinogen gene polymorphisms are associated with plasma fibrinogen and
      coronary artery disease in patients with myocardial infarction. The ECTIM Study.
      Etude Cas-Temoins sur l'Infarctus du Myocarde.
AB  - BACKGROUND: Polymorphisms of the beta fibrinogen gene have been shown to affect
      plasma fibrinogen levels and the risk of peripheral arterial disease. We now
      present the results of a detailed analysis of the beta fibrinogen gene in
      relation to plasma fibrinogen and to the severity of coronary artery disease
      (CAD) in patients with myocardial infarction (MI) in the ECTIM Study. METHODS AND
      RESULTS: Ten polymorphisms of the beta fibrinogen gene, including five new
      polymorphisms identified by single-strand conformation polymorphism analysis, and
      one polymorphism in the 3' flanking region of the alpha fibrinogen gene were
      investigated in 565 patients with MI and 668 control subjects. The polymorphisms
      were in tight linkage disequilibrium and the genotype frequencies were similar in
      patients with MI and control subjects. In the multivariate analysis, only two
      polymorphisms, beta Hae III (P < .0003) and beta-854 (P < .01), were
      independently associated with plasma fibrinogen. The significant association
      between beta fibrinogen polymorphisms and plasma fibrinogen was present in
      smokers but not in nonsmokers. In French MI patients, the number of coronary
      arteries with > 50% stenosis was estimated by angiography and used as a criterion
      for severity of CAD. Presence of the less frequent allele of the beta Bcl I (P <
      .0003) and of other polymorphisms was positively associated with the severity of
      CAD. CONCLUSIONS: Genetic variants of the beta fibrinogen gene are associated
      with an increased plasma level of fibrinogen, especially in smokers. The
      association with CAD appears to be the consequence of an increased risk of MI in
      subjects with severe CAD who carry the predisposing beta fibrinogen genotypes.

PMID- 8565161
TI  - Smoking, serum lipids, blood pressure, and sex differences in myocardial
      infarction. A 12-year follow-up of the Finnmark Study.
AB  - BACKGROUND: Few epidemiological studies have investigated the relative importance
      of major coronary risk factors in the two sexes within the same study population.
      In particular, it is not clear whether smoking carries a similar risk of coronary
      heart disease in men and women. METHODS AND RESULTS: The associations between
      smoking, serum lipids, blood pressure, and myocardial infarction were examined in
      a population-based prospective study of 11,843 men and women aged 35 to 52 years
      at entry. During 12 years, 495 cases of first myocardial infarction among men and
      103 cases among women were identified. Myocardial infarction incidence was 4.6
      times higher among men. The incidence was increased sixfold in women and
      threefold in men who smoked at least 20 cigarettes per day compared with never
      smokers, and the rate in female heavy smokers exceeded that of never-smoking men.
      Multivariate analysis identified current smoking as a stronger risk factor in
      women (relative risk, 3.3; 95% confidence interval [CI], 2.1 to 5.1) than in men
      (relative risk, 1.9; 95% CI, 1.6 to 2.3). Among those under 45 years old at
      entry, the smoking-related sex difference was more pronounced (in women: relative
      risk, 7.1; 95% CI, 2.6 to 19.1) (in men: relative risk, 2.3; 95% CI, 1.6 to 3.2).
      Serum total cholesterol, HDL cholesterol, and systolic blood pressure were also
      highly significant predictors in both sexes. CONCLUSIONS: Smoking was a stronger
      risk factor for myocardial infarction in middle-aged women than in men. Relative
      risks associated with serum lipids and blood pressure were similar despite large
      sex differences in myocardial infarction incidence rates.

PMID- 8565162
TI  - Early endothelial dysfunction predicts the development of transplant coronary
      artery disease at 1 year posttransplant.
AB  - BACKGROUND: Accelerated coronary arteriosclerosis is the major obstacle to long
      term survival after cardiac transplantation. Endothelial dysfunction is common
      early posttransplant. The relationship between early endothelial dysfunction and
      the development of allograft arteriosclerosis has not been analyzed serially with
      intravascular ultrasound in the same patients. We hypothesized that an early
      constrictor response to acetylcholine, indicative of endothelial dysfunction, may
      predict the development of transplant coronary arteriosclerosis. METHODS AND
      RESULTS: Endothelium-dependent vasomotion was assessed early posttransplant in 20
      patients by serial intracoronary acetylcholine infusion, and the percent change
      in diameter was measured by quantitative angiography. The development of
      arteriosclerosis was studied by use of intravascular ultrasound in the same 20
      patients by quantifying the changes in intimal index (delta Ii) and maximal
      intimal thickness [delta Mt] of 46 matched coronary segments between initial and
      1-year follow-up studies. Coronary segments with endothelial dysfunction
      (constriction > or = 5%; n = 23) demonstrated a significantly greater increase in
      mean Ii and Mt by 1 year posttransplant compared with segments with normal
      endothelial function (n = 23) (delta Ii = 7 +/- 2% versus 2 +/- 1% [P < .05] and
      delta Mt = 140 +/- 40 versus 50 +/- 20 microns [P < .05]). No other parameters
      examined predicted the development of allograft arteriosclerosis in the initial
      year posttransplant. CONCLUSIONS: Paired studies that used intravascular
      ultrasound showed that early endothelial dysfunction predicts the development of
      allograft arteriosclerosis during the initial year posttransplant. This early
      pathophysiological feature is likely an important marker that could be useful in
      therapeutic trials.

PMID- 8565163
TI  - Simultaneous transmission/emission myocardial perfusion tomography. Diagnostic
      accuracy of attenuation-corrected 99mTc-sestamibi single-photon emission computed
      tomography.
AB  - BACKGROUND: The purpose of the present study was to assess the diagnostic
      performance of attenuation-corrected (AC) stress 99mTc-sestamibi cardiac single
      photon emission computed tomography (SPECT) for the identification of coronary
      heart disease (CHD). METHODS AND RESULTS: With a triple-detector SPECT system
      with a 241Am transmission line source, simultaneous transmission/emission
      tomography (TCT/ECT) was performed on 60 patients with angiographic coronary
      disease and 59 patients with < or = 5% likelihood of CHD. Iteratively
      reconstructed AC stress 99mTc-sestamibi perfusion images were compared with
      uncorrected (NC) filtered-backprojection images. Normal database polar maps were
      constructed from AC and NC images for quantitative analyses. From the low
      likelihood patients, the visual and quantitative normalcy rates increased from
      0.88 and 0.76 for NC to 0.98 and 0.95 for AC (P < .05). For the detection of CHD,
      the receiver operating characteristic curves for the AC images demonstrated
      improved discrimination capacity (P < .05), and sensitivity/specificity values
      increased from 0.78/0.46 (NC) to 0.84/0.82 (AC) with visual analysis and from
      0.84/0.46 (NC) to 0.88/0.82 (AC) with quantitative analysis. For localization of
      stenosed vessels, visual and quantitative sensitivity values were 0.51 and 0.63
      for NC and 0.64 and 0.78 for AC images (P < .05), respectively. CONCLUSIONS:
      TCT/ECT myocardial perfusion imaging significantly improves the diagnostic
      accuracy of cardiac SPECT for the detection and localization of CHD. Clinical use
      of TCT/ECT imaging deserves serious consideration.

PMID- 8565164
TI  - Acute cardiovascular effects of OPC-18790 in patients with congestive heart
      failure. Time- and dose-dependence analysis based on pressure-volume relations.
AB  - BACKGROUND: OPC-18790 is a water-soluble quinolinone derivative that shares the
      pharmacological properties of vesnarinone and that may be useful for treating
      heart failure. We studied the contribution and relative dose sensitivities of the
      inotropic, lusitropic, and vascular effects of OPC-18790 in patients with dilated
      cardiomyopathy. METHODS AND RESULTS: Pressure-volume (PV) analysis was performed
      in 17 patients who received either 5 micrograms.kg-1.min-1 (low dose, n = 10) or
      10 micrograms.kg-1.min-1 (high dose, n = 7) OPC-18790 by 1-hour IV infusion.
      Right heart pressures and flow and left heart PV relations (conductance catheter)
      were measured at baseline and every 15 minutes during infusion. Transient
      inferior vena caval obstruction was used to determine PV relations. Both doses
      produced venodilation reflected by a 10% decline in left ventricular end
      diastolic volume and a 30% fall in atrial and pulmonary artery pressures.
      Arterial dilation was four times greater at the high dose, with an approximately
      40% fall in effective arterial elastance and systemic resistance. Contractility
      rose by 25% to 100% (depending on PV index) with both doses. Ventricular-arterial
      coupling (ratio of ventricular end-systolic to arterial elastances) was
      approximately 0.25 at baseline and doubled (or tripled) at low (or high) dose,
      correlating with improved efficiency. Isovolumetric relaxation shortened, whereas
      the diastolic PV relation was generally unchanged. Heart rate was unaltered.
      CONCLUSIONS: OPC-18790 has potent venous and arterial vasodilator effects and
      moderate inotropic and lusitropic effects without a change in heart rate. These
      combined actions suggest a unique potential of OPC-18790 for heart failure
      treatment.

PMID- 8565165
TI  - Clinical significance of the pulmonary vasodilator response during short-term
      infusion of prostacyclin in primary pulmonary hypertension.
AB  - BACKGROUND: The short-term vasodilator response to prostacyclin (PGI2) in
      patients with primary pulmonary hypertension (PPH) is not only unpredictable but
      also extremely variable in magnitude. In this retrospective study, we attempted
      to evaluate in a nonselected population of patients with PPH the degree of
      vasodilatation achieved during short-term infusion of PGI2 and to investigate
      whether patients with PPH differed in terms of baseline characteristics and
      prognoses, according to the level of vasodilatation achieved during initial
      testing with PGI2. METHODS AND RESULTS: Between 1984 and 1992, 91 consecutive
      patients with PPH underwent catheterization of the right side of the heart with a
      short-term vasodilator trial with PGI2 (5 to 10 ng.kg-1.min-1). According to the
      level of vasodilatation achieved during PGI2 infusion, patients were divided into
      three groups: nonresponding (NR, n = 40), moderately responding (MR, n = 42), and
      highly responding (HR, n = 9) patients. All three groups were defined by a
      decrease in total pulmonary resistance index (TPRi) of < 20%, between 20% and
      50%, and > 50%, respectively, relative to control values. Prolonged oral
      vasodilator therapy was subsequently started only in MR and HR patients. All
      patients had long-term oral anticoagulant therapy. The survival rate at 2 years
      (transplant recipients excluded) was significantly higher in HR patients compared
      with NR and MR patients (62% versus 38% and 47% survivors, respectively; P <
      .05). Comparisons between groups showed no significant differences in baseline
      hemodynamics or clinical characteristics except for a longer time between onset
      of symptoms and diagnosis (ie, first catheterization) of PPH in HR patients than
      in NR and MR patients (71 +/- 61 versus 35 +/- 34 and 21 +/- 21 months,
      respectively; P < .05). CONCLUSIONS: In this study, patients with PPH exhibiting
      a decrease in TPRi > 50% during short-term PGI2 challenge at the time of
      diagnosis had longer disease evolutions and better prognoses than patients with a
      lower vasodilator response.

PMID- 8565166
TI  - Cost-effectiveness of implantable defibrillator as first-choice therapy versus
      electrophysiologically guided, tiered strategy in postinfarct sudden death
      survivors. A randomized study.
AB  - BACKGROUND: Rising costs of health care, partly as a result of costly therapeutic
      innovations, are of concern to both the medical profession and healthcare
      authorities. The implantable cardioverter-defibrillator (ICD) is still not
      remunerated by Dutch healthcare insurers. The aim of this study was to evaluate
      the cost-effectiveness of early implantation of the ICD in postinfarct sudden
      death survivors. METHODS AND RESULTS: Sixty consecutive postinfarct survivors of
      cardiac arrest caused by ventricular tachycardia or fibrillation were randomly
      assigned either ICD as first choice (n = 29) or a tiered therapy starting with
      antiarrhythmic drugs and guided by electrophysiological (EP) testing (n = 31).
      Median follow-up was 729 days (range, 3 to 1675 days). Fifteen patients died, 4
      in the early ICD group and 11 in the EP-guided strategy group (P = .07). For
      quantitative assessment, the cost-effectiveness ratio was calculated for both
      groups and expressed as median total costs per patient per day alive. Because
      effectiveness aspects other than mortality are not incorporated in this ratio,
      other factors related to quality of life were used as qualitative measures of
      cost-effectiveness. The cost-effectiveness ratios were $63 and $94 for the early
      ICD and EP-guided strategy groups, respectively, per patient per day alive. This
      amounts to a net cost-effectiveness of $11,315 per patient per year alive saved
      by early ICD implantation. Costs in the early ICD group were higher only during
      the first 3 months of follow-up, but as a result of the high proportion of
      therapy changes, including arrhythmia surgery and late ICD implantation, costs in
      the EP-guided strategy group became higher after that. Patients discharged with
      antiarrhythmic drugs as sole therapy had the lowest total costs. This subset,
      however, showed extremely high mortality, resulting in a poor cost-effectiveness
      ratio ($196 per day). Invasive therapies and hospitalization were the major
      contributors to costs. If quality-of-life measures are taken into account, the
      cost-effectiveness of early ICD implantation was even more favorable. Recurrent
      cardiac arrest and cardiac transplantation occurred in the EP-guided strategy
      group only, whereas exercise tolerance, total hospitalization duration, number of
      invasive procedures, and antiarrhythmic therapy changes were significantly in
      favor of early ICD implantation. CONCLUSIONS: In terms of cost-effectiveness,
      early ICD implantation is superior to the EP-guided therapeutic strategy in
      postinfarct sudden death survivors.

PMID- 8565167
TI  - Anatomic substrate for idiopathic left ventricular tachycardia.
AB  - BACKGROUND: Idiopathic left ventricular tachycardia (ILVT) characterized by QRS
      complexes with right bundle-branch block (RBBB) morphology and left axis
      deviation is a distinct clinical syndrome that also demonstrates a characteristic
      response to verapamil and inducibility from the atrium in patients without
      structural heart disease. A false tendon has been described in the left ventricle
      in a patient with ILVT in whom surgical resection of the false tendon resulted in
      cure. We hypothesized that the false tendon is responsible for the genesis of
      similar ventricular tachycardia (VT) in others. METHODS AND RESULTS: We performed
      transthoracic (TTE) and/or transesophageal (TEE) two-dimensional echocardiograms
      in 15 patients undergoing catheter ablation for ILVT. There were 12 men and 3
      women (mean age, 31 +/- 12 years, with average symptom duration of 11 +/- 9
      years). The mean VT cycle length was 360 +/- 70 ms, and all had RBBB morphology
      with left axis deviation. Cardiac chamber sizes, left ventricular wall thickness,
      and wall motion were normal in all ILVT patients. TTE and/or TEE demonstrated a
      false tendon extending from the posteroinferior left ventricular free wall to the
      left ventricular septum in all ILVT patients. The false tendons were thick (> or
      = 2 mm maximal thickness) in 5 patients and thin (< 2 mm maximal thickness) in 10
      patients. We compared ILVT patients with a control group of 671 consecutive
      patients referred for echocardiography for other reasons. The mean age for the
      control group was 42 years. A false tendon was seen in the left ventricle in 34
      of 671 (5%). In the control group patients with a false tendon, 2 patients had a
      history of VT (left bundle-branch block morphology) and 1 had ventricular
      fibrillation. The false tendons in the control patients were also oriented
      transversely across the ventricular cavity but were somewhat thinner (< 2 mm
      maximal thickness in 32 of 34 patients). Catheter ablation with the use of
      radiofrequency and/or direct current applied to the posteroapical septum resulted
      in cure in 14 of 15 patients. CONCLUSIONS: A false tendon extending from the
      posteroinferior left ventricle to the septum is a consistent finding in patients
      with ILVT and probably is responsible for this unique arrhythmia. The mechanism
      by which the false tendon precipitates tachycardia is speculative, but
      possibilities include conduction through the false tendon or by producing stretch
      in the Purkinje fiber network on the interventricular septum.

PMID- 8565168
TI  - Ablation of 'incisional' reentrant atrial tachycardia complicating surgery for
      congenital heart disease. Use of entrainment to define a critical isthmus of
      conduction.
AB  - BACKGROUND: Intra-atrial reentrant tachycardia occurs frequently after surgery
      for congenital heart disease and is difficult to treat. We tested the hypotheses
      that intra-atrial reentrant tachycardia in patients who had undergone prior
      reparative surgery for congenital heart disease could be successfully ablated by
      targeting a protected isthmus of conduction bounded by natural and surgically
      created barriers and that entrainment techniques could be used to identify these
      zones. METHODS AND RESULTS: Eighteen consecutive patients with 26 intra-atrial
      reentrant tachycardias complicating surgery for congenital heart disease (9
      atrial septal defect repair, 4 Fontan, 2 Mustard, 2 Senning, and 1 Rastelli
      procedure) underwent electrophysiological study and ablation attempts. Mapping of
      activation was facilitated by the deployment of catheters with multiple
      electrodes. Sites for ablation were sought that demonstrated entrainment with
      concealed fusion and at which the postpacing interval minus the tachycardia cycle
      length and the stimulus to P wave minus the activation time were < 30 ms. These
      sites were considered to be within a narrow isthmus critical to the tachycardia
      mechanism. Anatomic barriers bordering the critical isthmus of conduction were
      identified on anatomic grounds, by the presence of areas of electrical silence or
      by the demonstration of split potentials signifying a line of block. Success was
      achieved in 15 patients with 21 arrhythmias. The median number of radiofrequency
      applications was 5. There was a wide range of activation times at successful
      sites (-30 to -250 ms). At a mean duration of follow-up of 17 +/- 8 months, 11
      patients were asymptomatic and 9 did not require antiarrhythmia therapy.
      CONCLUSIONS: Successful ablation of intra-atrial reentrant tachycardia
      complicating surgery for congenital heart disease may be achieved by creation of
      an ablative lesion in a critical isthmus of conduction bounded by anatomic
      barriers. This isthmus may be identified by the presence of entrainment with
      concealed fusion and an analysis of the relationship between the postpacing
      interval and the tachycardia cycle length and between the activation time and the
      stimulus time. Because this isthmus is invariably confined on at least one aspect
      by a surgical repair site that is of central importance to the tachycardia
      mechanism, we suggest that this type of arrhythmia be given the descriptive
      designation of "incisional reentry."

PMID- 8565169
TI  - Quantitative assessment of the spatial organization of atrial fibrillation in the
      intact human heart.
AB  - BACKGROUND: Atrial activation during atrial fibrillation (AF) is frequently
      described as random or chaotic. We propose that activation during AF is
      constrained by the principles of reentrant excitation; that these constraints
      impart a measurable spatial organization to activation during AF; and that the
      distance over which activation sequences remain well correlated can be readily
      measured and related both to the propensity of AF to sustain itself as well as to
      atrial tissue wavelength. METHODS AND RESULTS: We describe a novel signal
      processing technique that quantifies the correlation in activation sequences
      recorded from five equally spaced sites in the right atrium in patients
      undergoing electrophysiology studies. In 20 patients in AF (12 with paroxysmal
      AF, 5 with chronic AF, and 3 with no clinical history of AF), the average
      correlation was 0.54 +/- 0.12 at 11 mm and 0.32 +/- 0.11 at 44 mm, compared with
      0.95 +/- .023 and 0.91 +/- .023 in sinus rhythm. In AF, the correlation versus
      distance relation was monotonically decreasing, well fit by a decaying
      exponential function. The space constant of this exponential function, termed the
      activation space constant, provides a single objective metric of the spatial
      organization of activation during AF. The mean activation space constant for the
      group was 2.6 +/- 1.15 cm. Chronic AF had the lowest mean activation space
      constant (1.84 +/- 0.36 cm) and AF in patients with no prior history of AF had
      the highest (3.06 +/- 0.40 cm) (P < .05), with paroxysmal AF characterized by
      intermediate values (2.80 +/- 1.4 cm). CONCLUSIONS: Using a novel method to
      measure the spatial organization of atrial activation during AF, we have
      demonstrated that AF in the intact human heart is organized over a length scale
      consistent with reentrant excitation. Preliminary results suggest a relationship
      between measured spatial organization and the clinical course of the arrhythmia.
      Further work is needed to determine whether measurement of spatial organization
      may be useful in prospective patient-specific selection of therapeutic options.

PMID- 8565170
TI  - Exploration of the precision of classifying sudden cardiac death. Implications
      for the interpretation of clinical trials.
AB  - BACKGROUND: As cardiovascular clinical trials improve in sophistication and
      therapies target specific cardiac mechanisms of death, a more objective and
      precise system to identify specific cause of death is needed. Ideally, sudden
      cardiac death would describe patients dying of ventricular tachycardia and
      ventricular fibrillation. In this context, we explored the precision of current
      sudden death classification and implications for clinical trials. METHODS AND
      RESULTS: Deaths were analyzed in 834 patients who received an automatic
      implantable cardioverter-defibrillator (ICD). Three arrhythmia experts used a
      standard prospective classification system to classify deaths into accepted
      categories: sudden cardiac, nonsudden cardiac, and noncardiac. New aspects to
      this study included analysis of autopsy results and ICD interrogation for
      arrhythmias at the time of death. All of the patients receiving the ICD
      previously had documented sustained ventricular tachycardia/fibrillation or
      cardiac arrest. Of the 109 subsequent deaths in the 834-patient database, 17
      (16%) were classified as sudden cardiac. Compared with the nonsudden cardiac and
      noncardiac categories, sudden cardiac death was more often identified in
      outpatients (59% versus 10%) and witnessed less often (41% versus 86%; both P <
      .001). The autopsy information contradicted and changed the clinical perception
      of a "sudden cardiac death" in 7 cases (myocardial infarction [n = 1], pulmonary
      embolism [n = 2], cerebral infarction [n = 1], ruptured thoracic [n = 1], and
      abdominal aortic aneurysms [n = 2]). Interpretable ICD interrogation was
      available in 53% of the deaths (47% unavailable: buried, programmed off, or other
      technical reasons). When evaluated, only 7 of 17 "sudden deaths" were associated
      with ICD discharges near the time of death. CONCLUSIONS: Even in a group of
      patients with an ICD, deaths classified as sudden cardiac frequently were not
      associated with ventricular tachycardia or ventricular fibrillation and were
      often noncardiac. It is possible to create a wide range of sudden cardiac death
      rates (more than fourfold) using the identical clinical database despite
      objective, prespecified criteria. Autopsy results frequently reveal noncardiac
      causes of clinical events simulating sudden cardiac death. ICD interrogation
      revealed that ICD discharges were often related to terminal arrhythmias
      incidental to the primary pathophysiological process leading to death.

PMID- 8565171
TI  - Left ventricular fibromuscular band is not a specific substrate for idiopathic
      left ventricular tachycardia.
AB  - BACKGROUND: A fibromuscular band has been detected in patients with idiopathic
      left ventricular tachycardia, and this band has been suggested to be the anatomic
      substrate for the arrhythmia. Whether the fibromuscular band is a specific
      substrate for the tachycardia was systematically evaluated in a large group of
      consecutive patients with and without idiopathic left ventricular tachycardia.
      METHODS AND RESULTS: Conventional transthoracic two-dimensional echocardiography
      and multiplane transesophageal echocardiography were performed in 18 patients
      with idiopathic left ventricular tachycardia that was responsive to calcium
      blockers (group 1, tachycardia patients) and 40 patients with paroxysmal
      supraventricular tachycardia (group 2, control patients). There were 17 men and 1
      woman, with a mean age of 29 +/- 11 years, in group 1 patients, and 21 men and 19
      women, with a mean age of 42 +/- 12 years, in group 2 patients. The QRS
      morphology during tachycardia in group 1 patients displayed a pattern of right
      bundle-branch block with superior axis in 15 patients, indeterminate axis in 2
      patients, and inferior axis in 1 patient. Radiofrequency ablation successfully
      eliminated the tachycardia in all 18 patients; the successful ablation site was
      located at the inferior apical septum in 11 patients, at the midseptum in 6
      patients, and at the anterior lateral wall in 1 patient. Transthoracic
      echocardiography detected the fibromuscular band in 11 of the 18 patients,
      whereas multiplane transesophageal echocardiography detected the band in 17 of 18
      patients. The fibromuscular band extended from the interventricular septum to the
      apex of the left ventricle. In group 2 patients, transthoracic echocardiography
      detected the fibromuscular band in 22 and multiplane transesophageal
      echocardiography detected the band in 35 of the 40 patients. The presence of a
      fibromuscular band in these two groups of patients was not statistically
      different. CONCLUSIONS: The presence of a left ventricular fibromuscular band is
      not a specific anatomic substrate for idiopathic left ventricular tachycardia.

PMID- 8565172
TI  - Inhibition of neointimal proliferation with low-dose irradiation from a beta
      particle-emitting stent.
AB  - BACKGROUND: Restenosis after successful percutaneous transluminal coronary
      angioplasty is the major factor limiting the long-term effectiveness of this
      procedure. Neointimal proliferation in response to arterial injury is an
      important contributor to restenosis. The use of radiation for the treatment of
      malignant and benign proliferative conditions has been well established. External
      beam irradiation and endovascular irradiation by use of an after-loading
      technique have been shown to inhibit neointimal proliferation in experimental
      models of restenosis. The objective of this study was to investigate whether low
      dose irradiation from a beta-particle-emitting stent would inhibit neointimal
      proliferation after placement in porcine iliac arteries. METHODS AND RESULTS:
      Fourteen titanium-mesh stents were implanted in the iliac arteries of nine NIH
      miniature swine. There were seven beta-particle-emitting radioisotope stents
      (32P, activity level 0.14 microCi) and seven control stents (31P,
      nonradioactive). Treatment effect was assessed by angiography and
      histomorphological examination of the stented iliac segments 28 days after
      implantation. There was a significant reduction in neointimal area (1.76 +/- 0.37
      mm2 versus 2.81 +/- 1.22 mm2, P = .05) and percent area stenosis (24.6 +/- 2.9%
      versus 36.0 +/- 10.7%, P = .02) within the beta-particle-emitting stents compared
      with the control stents. Neointimal thickness, which was assessed at each wire
      site, was also significantly less within the treatment stents (0.26 +/- 0.04 mm
      versus 0.38 +/- 0.10 mm, P = .012). Scanning electron microscopy was performed on
      sections from four stents. This demonstrated endothelialization of both the
      treatment and control stents. There was no excess inflammatory reaction or
      fibrosis in the media, adventitia, or perivascular space of vessels treated with
      the beta-particle-emitting stent compared with control vessels. At 28 days, there
      was no difference in smooth muscle cell proliferation as measured by the
      proliferating cell nuclear antigen index. CONCLUSIONS: A local, continuous source
      of low-dose endovascular irradiation via a beta-particle-emitting stent inhibits
      neointimal formation in porcine arteries. This low dose of local irradiation did
      not prevent endothelialization of the stents. This novel technique offers promise
      for the prevention of restenosis and warrants further investigation.

PMID- 8565173
TI  - Oral antiplatelet, antithrombotic efficacy of DMP 728, a novel platelet
      GPIIb/IIIa antagonist.
AB  - BACKGROUND: Currently used antiplatelet drugs, including aspirin and ticlopidine,
      are effective against certain but not all of the many endogenous platelet
      activators. Because of their limited efficacy, a significant number of serious
      thromboembolic complications still occur, highlighting the need for a more
      effective therapy. DMP 728 has been characterized as a potent and specific
      platelet glycoprotein IIb/IIIa complex (GPIIb/IIIa) antagonist. The goals of the
      present study were to determine the oral antiplatelet and antithrombotic
      efficacies of DMP 728 in various arterial thrombosis models in dogs. METHODS AND
      RESULTS: In conscious and anesthetized mongrel dogs, DMP 728 at 0.02 to 1.0 mg/kg
      PO in gelatin capsules produced dose-dependent antiplatelet effects in inhibiting
      ex vivo platelet aggregation induced by ADP and prolonging template bleeding
      time. DMP 728 effects on bleeding time prolongation could be reversed more
      rapidly than those on platelet aggregation inhibition. A maximal antiplatelet
      effect for DMP 728 was demonstrated at 1.0 mg/kg PO. DMP 728 demonstrated dose
      dependent oral antiplatelet effects with an absolute oral bioavailability of 8%
      to 12% in dogs. Additionally, the antithrombotic efficacy of DMP 728 was examined
      after intravenous and oral administration at different doses in various models of
      arterial thrombosis. In the coronary artery Folts' model in dogs, DMP 728
      demonstrated maximal antithrombotic efficacy at 0.01 mg/kg IV and < 0.6 mg/kg PO.
      Additionally, DMP 728 at 0.1 and 1.0 mg/kg IV or PO demonstrated 60% to 100%
      prevention of primary thrombosis (P < .01) in an electrolytically induced carotid
      artery thrombosis model in dogs. CONCLUSIONS: These data suggest that DMP 728, a
      low-molecular-weight GPIIb/IIIa receptor antagonist, may have therapeutic
      potential as an oral antithrombotic agent in coronary and carotid artery
      thromboembolic disorders.

PMID- 8565174
TI  - Angiotensin-converting enzyme inhibition preserves endothelium-dependent coronary
      microvascular responses during short-term ischemia-reperfusion.
AB  - BACKGROUND: Chronic angiotensin-converting enzyme (ACE) inhibition initiated days
      to weeks after acute myocardial infarction can reduce ventricular dilatation and
      improve patient survival. However, the effects on coronary vascular and
      myocardial function of very early ACE inhibitor therapy for acute myocardial
      infarction remain unresolved. METHODS AND RESULTS: Hemodynamics, segmental
      shortening, coronary blood flow, and in vitro coronary microvascular relaxation
      responses were studied in noninstrumented control pigs (n = 8) and pigs subjected
      to 30 minutes of left anterior descending ischemia followed by administration of
      30 mL IV normal saline (IR-saline, n = 8), 5 mg/kg IV captopril (IR-captopril, n
      = 6), or 1.5 mg/kg IV enalaprilat (IR-enalaprilat, n = 6) before 1 hour of
      reperfusion. Hemodynamics were similar at baseline, end of ischemia, and end of
      reperfusion. However, coronary blood flow immediately on reperfusion was
      significantly enhanced in the IR-enalaprilat cohort (59 +/- 10 mL/min) compared
      with the IR-saline group (32 +/- 3 mL/min, P < .05). Segmental shortening in the
      dyskinetic ischemic region improved only minimally at the end of reperfusion to 1
      +/- 2%, -7 +/- 3%, and -2 +/- 6% for the IR-saline, IR-captopril, and IR
      enalaprilat groups, respectively (P < .05, IR-captopril versus IR-saline).
      Arteriolar microvascular endothelium-dependent responses to ADP (P < .01) and
      calcium ionophore A23187 (P < .01) were impaired after ischemia-reperfusion,
      whereas bradykinin responses were preserved (P = .95). Endothelium-dependent
      venular responses to ADP and serotonin were maintained despite ischemia
      reperfusion. Endothelium-independent responses to sodium nitroprusside were
      unaltered in arterioles and venules. Either captopril or enalaprilat restored ADP
      and A23187 arteriolar responses to control levels and increased bradykinin
      responses above control levels. CONCLUSIONS: Brief ischemia followed by
      reperfusion induces arteriolar microvascular endothelial dysfunction, while
      venular endothelial function is preserved in this porcine model. ACE inhibition
      enhances coronary blood flow at the time of reperfusion and can prevent
      impairment of endothelium-dependent arteriolar responses. However, ACE inhibition
      does not enhance ventricular segmental shortening acutely despite improved
      microvascular endothelial function and augmented postischemic coronary blood flow
      in this model of ischemia-reperfusion.

PMID- 8565175
TI  - 1,3 Butadiene, a vapor phase component of environmental tobacco smoke,
      accelerates arteriosclerotic plaque development.
AB  - BACKGROUND: Our recent results support predictions from epidemiology studies that
      thousands of excess heart disease-related deaths result yearly in the United
      States from involuntary exposure to environmental tobacco smoke (ETS). Limited
      exposures of cockerels to ETS significantly accelerate arteriosclerosis. Despite
      little direct in vivo support, tar fraction rather than vapor phase compounds are
      considered largely responsible for the plaque-promoting effects of cigarette
      smoke. Here, we evaluate the effects of two ETS components on plaque development:
      the vapor phase component, 1,3 butadiene, and the tar component, the tobacco
      specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). At
      relatively high doses, injected NNK is carcinogenic in rodents. Epidemiology
      studies have identified increased mortality from arteriosclerotic heart disease
      among black men working in the butadiene rubber industry. Neither butadiene nor
      NNK has been tested experimentally for a possible role in plaque development.
      METHODS AND RESULTS: Cockerels inhaled butadiene (20 ppm; 16 weeks) or were
      injected biweekly with NNK (10 mg/kg, 16 weeks). Control cockerels were exposed
      to filtered air or were injected with the NNK solvent dimethylsulfoxide. Plaque
      incidence, prevalence, location, and size were determined double-blind. NNK had
      no significant effect on any of these measurements. In contrast, butadiene
      elicited a statistically significant increase in plaque size comparable to that
      seen after steady-state exposure to ETS from 5 cigarettes. CONCLUSION: (1) This
      study represents the first time that a single cigarette smoke component has been
      demonstrated to accelerate arteriosclerosis, at a dose that is environmentally
      relevant. (2) The plaque-promoting components of ETS may reside in the vapor
      phase. (3) The cockerel model should be valuable in understanding the mechanism
      underlying the reported increases in heart disease deaths among black workers in
      the butadiene rubber industry.

PMID- 8565176
TI  - Dose-dependent effect of endothelin-1 on blood flow to normal and collateral
      dependent myocardium.
AB  - BACKGROUND: Plasma levels of endothelin-1 (ET-1) increase during ischemia and
      could potentially contribute to impairment of myocardial blood flow (MBF).
      Because collateral vessels demonstrate enhanced responsiveness to certain
      vasoconstrictors, blood flow to collateral-dependent myocardium could be
      particularly sensitive to increases in ET-1 levels. METHODS AND RESULTS: Studies
      were performed in 13 dogs in which collateral vessel development was produced by
      fluoroscopic embolization of the midleft anterior descending coronary artery with
      a hollow plug 4 to 6 weeks before the study. MBF was measured with radioactive
      microspheres at baseline and during 30-minute infusions of ET-1 (1, 10, and 100
      ng/min) into the left main coronary artery. Because ET-1 stimulates endothelial
      prostacyclin release, aortic and coronary sinus levels of ET-1 and 6-keto
      prostaglandin F1 alpha were measured at the end of each infusion. ET-1 increased
      MBF from 0.82 mL.min-1.g-1 at baseline to 0.92 mL.min-1.g-1 at 10 ng/min (P <
      .05), which corresponded to a coronary plasma concentration of 73 +/- 16 pg/mL.
      Blood flow in the collateral zone was less (0.74 mL.min-1.g-1) than in the normal
      zone (P < .05) and did not increase at an ET-1 dose of 10 ng/min. MBF in the
      normal and collateral zones significantly decreased when ET-1 was increased to
      100 ng/min, corresponding to a coronary sinus concentration of 175 +/- 45 pg/mL
      (P < .05). ET-1 produced dose-related increases in aortic and coronary sinus 6
      keto-prostaglandin F1 alpha and the transcoronary difference (P < .05). To assess
      the importance of prostacyclin in opposing the vasoconstriction produced by ET-1,
      additional studies were performed after cyclooxygenase blockade with
      indomethacin. After indomethacin administration, ET-1 (10 ng/min) caused a 120 +/
      23% increase in collateral vascular resistance (P < .05) and abolished the
      vasodilation that this dose produced in the normal zone. CONCLUSIONS: Blood flow
      to normal myocardium is increased at moderate plasma elevations of ET-1, whereas
      collateral blood flow is unchanged. Only at significantly elevated plasma
      concentrations of ET-1 is blood flow to normal and collateral-dependent
      myocardium impaired. Coronary endothelial production of prostacyclin in response
      to increasing concentrations of ET-1 represents an important means of blunting
      the vasoconstrictor properties of ET-1 in the canine coronary circulation.
      Coronary collateral vessels demonstrate a much greater dependence on prostacyclin
      production in blunting the vasoconstrictor properties of ET-1.

PMID- 8565177
TI  - Accurate three-dimensional reconstruction of intravascular ultrasound data.
      Spatially correct three-dimensional reconstructions.
AB  - BACKGROUND: The geometrical accuracy of conventional three-dimensional (3D)
      reconstruction methods for intravascular ultrasound (IVUS) data (coronary and
      peripheral) is hampered by the inability to register spatial image orientation
      and by respiratory and cardiac motion. The objective of this work was the
      development of improved IVUS reconstruction techniques. METHODS AND RESULTS: We
      developed a 3D position registration method that identifies the spatial
      coordinates of an in situ IVUS catheter by use of simultaneous ECG-gated biplane
      digital cinefluoroscopy. To minimize distortion, coordinates underwent pincushion
      correction and were referenced to a standardized calibration cube. Gated IVUS
      data were acquired digitally, and the spatial locations of the imaging planes
      were then transformed relative to their respective 3D coordinates, rendered in
      binary voxel format, resliced, and displayed on an image-processing workstation
      for off-line analysis. The method was tested by use of phantoms (straight tube,
      360 degrees circle, 240 degrees spiral) and an in vitro coronary artery model. In
      vivo feasibility was assessed in patients who underwent routine interventional
      coronary procedures accompanied by IVUS evaluation. Actual versus calculated
      point locations were within 1.0 +/- 0.3 mm of each other (n = 39). Calculated
      phantom volumes were within 4% of actual volumes. Phantom 3D reconstruction
      appropriately demonstrated complex morphology. Initial patient evaluation
      demonstrated method feasibility as well as errors if respiratory and ECG gating
      were not used. CONCLUSIONS: These preliminary data support the use of this new
      method of 3D reconstruction of vascular structures with use of combined vascular
      ultrasound data and simultaneous ECG-gated biplane cinefluoroscopy.

PMID- 8565179
TI  - Enhanced regional deformation at the anterior papillary muscle insertion site
      after chordal transsection.
AB  - BACKGROUND: Clinical and experimental studies of mitral valve replacement have
      shown a depression of ventricular function after chordal transsection; most
      recent studies have proposed that this is secondary to a depression of local
      function near the papillary muscle insertion site. However, there is no direct
      experimental evidence for changes in local fiber shortening in the wall of the
      left ventricle overlying the papillary muscle. Accordingly, we investigated the
      effect of chordal transsection on left ventricular shape and on three-dimensional
      regional deformation of the myocardium near the insertion of the anterior
      papillary muscle. METHODS AND RESULTS: In six open-chest dogs, two sets of three
      transmural columns of radiopaque markers were implanted in the anterior wall, one
      set at the tip of the papillary muscle (basal) and one at the site of papillary
      muscle fiber insertion (apical). A Bjork-Shiley mitral valve was placed in the
      left atrium adjacent to the native valve. Markers were then tracked with biplane
      cineradiography, and deformation was quantified with the use of finite strain
      analysis. Chordal transection resulted in reduced left ventricular end-systolic
      pressure and slowed relaxation. After chordal transsection, outward displacement
      of the ventricular wall and transverse shearing deformation were observed in the
      area of the papillary muscle during isovolumic contraction. Circumferential and
      radial strains during ejection were maintained at our basal site and enhanced on
      our apical site. CONCLUSIONS: Chordal transsection led to enhanced local
      shortening and wall thickening and regional strain nonuniformity. These results
      indicate that chordal transsection induces an unloading of myocardium at the
      papillary muscle insertion site and that the resulting heterogeneity of regional
      function is the mechanism for the reduced global function and slowed ventricular
      relaxation.

PMID- 8565178
TI  - Estrogen reduces myointimal proliferation after balloon injury of rat carotid
      artery.
AB  - BACKGROUND: Vascular disease progresses more slowly in females with functional
      ovaries than in males. The mechanisms of this vasoprotective effect of female sex
      are incompletely understood. This study tested (1) whether there is a sex
      difference in the development of myointimal proliferation after balloon injury of
      the rat carotid artery in vivo, (2) whether this response is estrogen or androgen
      dependent, and (3) whether there is a sexual dimorphism in expression of the c
      myc proto-oncogene in intact and/or damaged rat carotid arteries. METHODS AND
      RESULTS: Ten-week-old male and female Sprague-Dawley rats were either
      gonadectomized or studied intact. Gonadectomized rats of both sexes were
      implanted with estradiol, testosterone, or nothing (control) 3 days before
      vascular injury. Two weeks later, the rats were killed by overdose of
      pentobarbital, and the injured right and uninjured control left carotid arteries
      were fixed and subjected to morphometric analysis for evaluation of the degree of
      myointimal thickening. Separate groups of intact male and female rats were killed
      at 1 and 2 hours after vascular injury, and total RNA from injured and uninjured
      vessels was subjected to Northern blot analysis for assessment of steady state c
      myc mRNA levels. Neointimal area and the ratio of neointimal to medial area were
      significantly less in intact female rats than in intact male rats (P < .05).
      Gonadectomy of female rats was associated with a greater increase in neointima
      formation after balloon injury than that observed in intact females (P < .05),
      but testosterone replacement did not further enhance this response. Estradiol
      treatment significantly inhibited myointimal proliferation after vascular injury
      in gonadectomized rats of both sexes (P < .05). Neither gonadectomy nor
      gonadectomy plus testosterone replacement altered the myointimal proliferative
      response to balloon injury in male rats. Steady state c-myc mRNA levels were
      detectable in undamaged carotid arteries in intact rats of both sexes and were
      significantly greater in males than in females; c-myc mRNA levels were increased
      in both sexes after carotid injury, but the response was significantly larger in
      magnitude and more rapid in males than in females. CONCLUSIONS: These data
      indicate that the sex difference in myointimal proliferation after vascular
      injury is estrogen dependent. C-myc gene expression is greater in the undamaged
      carotid artery of the male than in that of the female, and the responsiveness of
      this gene to balloon injury of the artery is more rapid and more robust in the
      male than in the female rat. These findings have direct implications for the
      prevention and treatment of vascular disease in humans.

PMID- 8565180
TI  - Effective regurgitant orifice area by the color Doppler flow convergence method
      for evaluating the severity of chronic aortic regurgitation. An animal study.
AB  - BACKGROUND: The aim of the present study was to evaluate dynamic changes in
      aortic regurgitant (AR) orifice area with the use of calibrated electromagnetic
      (EM) flowmeters and to validate a color Doppler flow convergence (FC) method for
      evaluating effective AR orifice area and regurgitant volume. METHODS AND RESULTS:
      In 6 sheep, 8 to 20 weeks after surgically induced AR, 22 hemodynamically
      different states were studied. Instantaneous regurgitant flow rates were obtained
      by aortic and pulmonary EM flowmeters balanced against each other. Instantaneous
      AR orifice areas were determined by dividing these actual AR flow rates by the
      corresponding continuous wave velocities (over 25 to 40 points during each
      diastole) matched for each steady state. Echo studies were performed to obtain
      maximal aliasing distances of the FC in a low range (0.20 to 0.32 m/s) and a high
      range (0.70 to 0.89 m/s) of aliasing velocities; the corresponding maximal AR
      flow rates were calculated using the hemispheric flow convergence assumption for
      the FC isovelocity surface. AR orifice areas were derived by dividing the maximal
      flow rates by the maximal continuous wave Doppler velocities. AR orifice sizes
      obtained with the use of EM flowmeters showed little change during diastole.
      Maximal and time-averaged AR orifice areas during diastole obtained by EM
      flowmeters ranged from 0.06 to 0.44 cm2 (mean, 0.24 +/- 0.11 cm2) and from 0.05
      to 0.43 cm2 (mean, 0.21 +/- 0.06 cm2), respectively. Maximal AR orifice areas by
      FC using low aliasing velocities overestimated reference EM orifice areas;
      however, at high AV, FC predicted the reference areas more reliably (0.25 +/-
      0.16 cm2, r = .82, difference = 0.04 +/- 0.07 cm2). The product of the maximal
      orifice area obtained by the FC method using high AV and the velocity time
      integral of the regurgitant orifice velocity showed good agreement with
      regurgitant volumes per beat (r = .81, difference = 0.9 +/- 7.9 mL/beat).
      CONCLUSIONS: This study, using strictly quantified AR volume, demonstrated little
      change in AR orifice size during diastole. When high aliasing velocities are
      chosen, the FC method can be useful for determining effective AR orifice size and
      regurgitant volume.

PMID- 8565181
TI  - Optical mapping in a new guinea pig model of ventricular tachycardia reveals
      mechanisms for multiple wavelengths in a single reentrant circuit.
AB  - BACKGROUND: Although the relationship between cardiac wavelength (lambda) and
      path length importantly determines the stability of reentrant arrhythmias, the
      physiological determinants of lambda are poorly understood. To investigate the
      cellular mechanisms that control lambda during reentry, we developed an
      experimental system for continuously monitoring lambda within a reentrant circuit
      with the use of voltage-sensitive dyes and a new guinea pig model of ventricular
      tachycardia (VT). METHODS AND RESULTS: Action potentials were recorded
      simultaneously from 128 ventricular sites in Langendorff-perfused hearts (n = 15)
      in which propagation was confined to a two-dimensional rim of epicardium by an
      endocardial cryoablating procedure. The reentrant path was precisely controlled
      by creating an epicardial obstacle (2 x 10 mm) with an argon laser. To control
      for fiber orientation and rate-dependent membrane properties, lambda during
      reentry was compared with lambda during plane wave propagation transverse and
      longitudinal to cardiac fibers at a stimulus cycle length (CL) comparable to the
      VT CL. Reentrant VT (CL = 97.0 +/- 6.2 ms) was reproducibly induced by programmed
      stimulation in 93% of preparations. lambda varied considerably within the
      reentrant circuit (range, 10.6 to 22.5 mm), because of heterogeneities of
      conduction rather than action potential duration. lambda was significantly
      shorter during reentrant propagation (ie, with pivoting) parallel to fibers (10.6
      +/- 4.2 mm) compared with plane wave propagation (ie, without pivoting) parallel
      to fibers (32.8 +/- 6.5 mm, P < .02), indicating that wave-front pivoting was
      primarily responsible for shortening of lambda during reentry. The mechanism of
      lambda shortening was conduction slowing from increased current load experienced
      by the pivoting wave front. CONCLUSIONS: We provide direct experimental evidence
      that multiple wavelengths are present even within a relatively simple reentrant
      circuit. Abrupt changes in loading during wave-front pivoting, rather than
      membrane ionic properties or fiber structure, were a major determinant of lambda
      and, therefore, may play an important role in the stability of reentry.

PMID- 8565182
TI  - Images in cardiovascular medicine. Muscle bridging of the left anterior
      descending coronary artery.

PMID- 8565183
TI  - Enhanced intracoronary thrombosis using a novel local drug delivery system.

PMID- 8565184
TI  - Combined restrictive cardiomyopathy and constrictive pericarditis.

PMID- 8565185
TI  - Clinicopathological Conference.

PMID- 8565186
TI  - Dobutamine, dipyridamole, and stress echocardiography.

PMID- 8565187
TI  - The abstractness of the word 'abstract'.

PMID- 8565188
TI  - Infarct mortality: an age-old or old-age problem?

PMID- 8565189
TI  - Circadian variation in ventricular refractoriness.

PMID- 8565190
TI  - Report of the National Eye Institute/Industry workshop on Clinical Trials in Dry
      Eyes.

PMID- 8565191
TI  - AIDS and the contact lens practice.
AB  - The probability of the ophthalmologist and office personnel coming into direct
      contact with a patient infected with the human immunodeficiency virus (HIV) is
      extremely high. HIV has been recovered from the ocular tissues, tears, and soft
      contact lenses of patients with acquired immunodeficiency syndrome. All
      ophthalmic offices, especially those with a contact lens practice, must be aware
      of any potential risk of transmission of HIV to both the office staff and to
      other patients from HIV-infected patients through the use of trial contact
      lenses. To date, there has been no documented case of HIV transmission through
      human tears or contact lenses, and the risk of such a transmission is extremely
      low.

PMID- 8565192
TI  - Evaluating the preservative effectiveness of RGP lens care solutions.
AB  - We examined the antimicrobial preservative efficacy of nine rigid gas permeable
      (RGP) contact lens care solutions by challenging them in a laboratory study with
      both standard test organisms and preservative-resistant strains. Solutions
      containing polyhexamethylene biguanide (PHMB), such as Boston Advance (15 ppm)
      and a Boston Advance Enhanced Comfort Formula (5 ppm PHMB + 30 ppm chlorhexidine
      gluconate [CHG]) were most effective at rapidly killing vegetative cells, killing
      all bacteria and yeast by 6 hours. Boston Advance only slightly reduced the
      number of Aspergillus niger spores during the 28 day study, but Boston Advance
      Enhanced Comfort Formula reduced the spores by almost 3 logs by 14 days and by 4
      logs by 21 days. Thimerosal-preserved Soaclens only reduced Staphylococcus aureus
      by 1 log at 6 hours, but at 1 day all tested organisms including S. aureus and A.
      niger were killed. Barnes Hind Gas Permeable Wetting and Soaking Solution,
      containing 50 ppm CHG, had little effect on adapted Serratia marcescens or
      Pseudomonas cepacia during the 28 day study. Allergan Wet-N-Soak Plus, containing
      30 ppm benzalkonium chloride (BAK), was also unable to kill adapted S. marcescens
      or P. cepacia. CIBA Vision Premus (40 ppm BAK) was unable to kill adapted S.
      marcescens. Alcon Opti-Free, with 50 ppm polyquaternium-1 (polyquad), did not
      kill P. cepacia. Sherman Stay-Wet 3, containing 0.1% benzyl alcohol, was not
      effective against S. marcescens (adapted or unadapted), P. cepacia, or A. niger.
      Sherman DeStat 3, which contains 0.1% benzyl alcohol plus surfactants and five
      times the concentration of EDTA as in Stay-Wet 3, was able to kill all the
      vegetative cells by 7 days but did not significantly reduce A. niger.

PMID- 8565194
TI  - Adherence of cysts and trophozoites of Acanthamoeba to unworn rigid gas permeable
      and soft contact lenses.
AB  - Contact lens related Acanthamoeba keratitis has been more often associated with
      the use of soft contact lenses than with the use of rigid gas permeable (RGP)
      contact lenses. We studied the adherence of Acanthamoeba cysts and trophozoites
      to unworn RGP (silicone acrylate and fluoropolymer) and low and high water
      content soft contact lenses marketed in India. A human corneal isolate of
      Acanthamoeba polyphaga suspended in saline (1 x 10(5) amoebae/mL) was used. Lens
      segments were exposed to A. polyphaga cysts or trophozoites with or without
      shaking. After exposure for zero to 7 hours, lenses were either washed or not
      washed and the adherence was determined using light microscopy and a
      hemocytometer (per square millimeter of the lens). Both cysts and trophozoites
      immediately adhered to all four types of lenses. Adhesion increased with an
      increase in exposure time. The number of adherent cysts and trophozoites was
      higher (P = 0.043-0.0003) in the unwashed group of lenses at all exposure times
      for all lenses. Among washed groups, adherence was greatest with RGP silicone
      acrylate and high water content soft lenses. Trophozoites of Acanthamoeba showed
      greater adherence to RGP lenses, whereas cysts showed greater adherence to high
      water content soft lenses. Shaking did not have a significant effect on
      adherence. Adhesion of Acanthamoeba to contact lenses may play an important role
      in the pathogenesis of Acanthamoeba keratitis.

PMID- 8565193
TI  - Resistance of adhered bacteria to rigid gas permeable contact lens solutions.
AB  - We examined eight conditioning or disinfecting solutions recommended for use with
      rigid gas permeable (RGP) or hard contact lenses for their efficacy against
      planktonic and attached cells of bacteria and Candida albicans. Most solutions,
      particularly those containing phenylmercuric nitrate and polyaminopropyl
      biguanide, gave marked inhibition (99.99% reduction within 4 hours) of planktonic
      cells of bacteria. Planktonic cells of Serratia marcescens and C. albicans
      survived in certain solutions containing chlorhexidine and benzalkonium chloride.
      In contrast, cells of all test microorganisms adhered to wells of polyethylene
      contact lens cases showed various degrees of survival after 4, 6, and 12 hours of
      exposure to most contact lens solutions. Drying of the lens case with adhered
      cells for 10 hours prior to addition of the lens solution usually reduced the
      incidence of recovery. Studies demonstrated that biofilms developed in cases with
      solutions of low and high efficacy. The enhanced resistance of adhered cells
      requires the periodic disinfection or replacement of lens cases used with RGP
      lenses.

PMID- 8565195
TI  - The use of collagen shields impregnated with amphotericin B to treat Aspergillus
      keratomycosis.
AB  - We treated three patients with Aspergillus keratomycosis with collagen shields
      soaked in amphotericin B (0.50%) for 2 hours at 25 degrees C before application.
      These shields, replaced daily, were used in conjunction with amphotericin B
      (0.25%) eye drops, which were applied every 2 hours. Cultures from the eyes of
      all patients became negative within 15 days of treatment. Subsequently, two
      patients required keratoplasty. The results suggest that collagen shields
      prepared this way deliver an adequate concentration of amphotericin B to the
      cornea, aid its tolerance, and improve the prognosis of Aspergillus
      keratomycosis. Further studies are needed to define the minimum therapeutic
      concentrations necessary to inhibit the growth of the fungus and to avoid a toxic
      effect on the cornea.

PMID- 8565196
TI  - Controlled comparison of two fluorometholone formulations in the antigen
      challenge model of allergic conjunctivitis.
AB  - We compared the safety and efficacy of MethaSite, a gel-forming suspension (0.1%
      fluorometholone), to a commercially available 0.1% fluorometholone ointment, FML
      S.O.P., using an antigen challenge model. Subjects with known allergic histories
      were exposed to increasing concentrations of cat dander, ragweed, or grass at
      visits 1 and 2. Allergic responses of conjunctival injection, chemosis, and
      subjective itching were quantified on a scale from zero to 3; the sum of these
      ratings constituted the total allergic score. At visit 3, 105 subjects with total
      scores of > or = 5 received a drop of MethaSite in one eye and a 0.5 inch ribbon
      of FML ointment in the other eye. Three and 6 hours postdose, the eyes were
      challenged with the antigen concentration that provoked significant allergic
      response at visit 2. We determined safety by evaluating changes in visual acuity,
      intraocular pressure, and biomicroscopy that occurred between visits 1 and 3.
      Eyes treated with MethaSite and FML responded similarly to the antigen
      challenges. Both groups demonstrated suppression of allergic response 3 and 6
      hours postdose through equivalent and significant reductions in total allergy
      scores and individual ratings of injection, chemosis, and itching. In this
      population, MethaSite was equivalent to FML ointment in safety and efficacy.

PMID- 8565197
TI  - Effect of sodium hyaluronate ophthalmic solution on peripheral staining of rigid
      contact lens wearers.
AB  - We evaluated the efficacy of sodium hyaluronate ophthalmic solutions on 3 and 9
      o'clock staining with rigid contact lens wearers in a double masked multicenter
      study involving four institutions and 43 patients. Both sodium hyaluronate (0.1%)
      and control ophthalmic solutions (artificial tears) without preservative were
      used. Patients were randomly divided into two groups. The test group received
      sodium hyaluronate ophthalmic solution, and the control group received artificial
      tears as a control ophthalmic solution. The agents were instilled six times per
      day for 2 weeks while patients wore contact lenses. Although subjective symptoms
      improved similarly in the two groups, slit lamp observation, corneal staining,
      and anterior segment photography demonstrated improved results in eyes having
      received sodium hyaluronate ophthalmic solutions. We conclude that sodium
      hyaluronate ophthalmic solution is effective and safe for treating 3 and 9
      o'clock staining in rigid contact lens wearers.

PMID- 8565198
TI  - Effects of long-term rigid contact lens wear on the endothelium of corneal
      transplants for keratoconus 10 years after penetrating keratoplasty.
AB  - Contact lenses do not appear to cause changes in endothelial cell density in
      normal individuals. In eyes with abnormal corneal endothelium, however, the
      effects of contact lens wear may be more severe. We studied eyes with abnormally
      enlarged endothelial cells resulting from penetrating keratoplasty (PK). We
      identified 34 patients with phakic corneal transplants for keratoconus that had
      the following characteristics: first graft, no rejection episodes, no
      reoperations, and follow-up examinations for at least 5 postoperative years.
      Fifteen of these patients had been fit with daily wear rigid contact lenses (12
      rigid gas permeable, 3 polymethylmethacrylate) postoperatively. Contact lens
      fitting occurred anywhere from 3 months to 2 years post-PK; 19 control subjects
      had not been fit with contact lenses. Twenty-one of the patients (nine contact
      lens wearers and 12 control subjects) were examined 10 years after keratoplasty.
      The contact lens group developed polymegethism, but there was no significant
      difference from the controls in endothelial cell density at 5 or 10 years post
      PK. The cell density at 10 years was 824 +/- 156 cells/mm2 (mean +/- SD) in the
      contact lens group and 833 +/- 167 cells/mm2 in the control group (P = 0.90). The
      endothelial cell loss 10 years after keratoplasty was 73% for both groups. Thus,
      we found no effect on endothelial cell density from at least 7 years of daily
      rigid contact lens wear in eyes with corneal transplants for keratoconus.

PMID- 8565199
TI  - High-frequency ultrasound spectral parameter imaging of anterior corneal scars.
AB  - High frequency (50-MHz) ultrasound allows greater resolution (approximately 30
      microns) and improved tissue differentiation of the anterior ocular structures
      than conventional (8-10 MHz) ultrasonic techniques. Spectral analysis of tissue
      acoustic backscatter is sensitive to both the concentration and size of tissue
      inhomogeneities. We studied the healing process of experimentally induced corneal
      scars using high frequency ultrasound spectral analysis. Scatterer size and
      concentration parameter images of scarred corneas showed distinctive patterns
      that were correlated with histology over time. This quantitative technique offers
      a new, noninvasive, in vivo method for the assessment of the internal
      microarchitecture of surgically altered corneal tissue and its healing dynamics.

PMID- 8565200
TI  - In vivo confocal microscopy of corneal wound healing after excimer laser
      photorefractive keratectomy.
AB  - We used real-time scanning confocal microscopy to evaluate early changes in
      corneal wound healing after excimer laser photorefractive keratectomy (PRK).
      Adult New Zealand White rabbits were given photorefractive keratectomy treatments
      appropriate for 5.00 to 8.00 D of myopia (44.5 to 71.0 micros depth, with a 5-mm
      diameter treatment zone). Daily confocal microscopic examinations showed acute
      loss of keratocytes in the anterior corneal stroma by 5 hours; losses were
      maximal between 24 and 48 hours for 5.00 D and 6.00 D ablations and between 72
      and 96 hours for 7.00 D and 8.00 D ablations. The oval nuclei of normal
      keratocytes gave way to spindle-shaped fibroblasts accompanied by an accumulation
      of fibrillary extracellular matrix. Fibroblasts density increased toward the end
      of the week. Deeper ablations resulted in a longer period of keratocyte depletion
      and delayed onset of fibroblast activity. No epithelial, deep stromal, or
      endothelial abnormalities were detected, nor was stromal inflammation found.
      Light microscopy 1 week after PRK revealed superficial fibroplasia, which
      correlated with the en face images obtained with real-time in vivo confocal
      microscopy. The confocal microscope has a number of advantages as a clinical tool
      for investigation of laser-induced changes in corneal keratocytes and the stromal
      matrix, which may play a role in determining visual outcome after PRK.

PMID- 8565201
TI  - Fitting contact lenses after excimer laser photorefractive keratectomy for
      myopia.
AB  - To compensate for undercorrection, regression, or irregular astigmatism, contact
      lenses are sometimes fit after excimer laser photorefractive keratectomy (PRK).
      We fit 13 eyes (eight patients) with aspheric rigid gas permeable (RGP) contact
      lenses following PRK. Patients were fit for various reasons, and they were all
      previous RGP contact lens wearers. Eight of 13 eyes could not be corrected with
      spectacles to the same acuity as before PRK. With RGP contact lenses, all
      patients were corrected to the same acuities as before PRK. The mean base curve
      of the preoperative RGP lenses was 7.98 +/- 0.36 mm (SD); the mean power was 
      5.92 D +/- 2.88 D (SD). Postoperative lenses had a mean base curve of 8.03 mm +/-
      0.41 mm (SD) and mean power of -5.5 D +/- 3.08 D (SD). Fitting RGP lenses after
      PRK was uncomplicated, and all lenses were as well tolerated after PRK as they
      had been before the procedure.

PMID- 8565202
TI  - Is bone alkaline phosphatase an adequate marker of bone metabolism during acute
      corticosteroid treatment?

PMID- 8565203
TI  - Simple, rapid nonradioactive method to detect major cystic fibrosis mutations in
      Ashkenazi Jews.

PMID- 8565204
TI  - Urinary sodium, potassium, calcium, urea, and creatinine determination by
      Ektachem 250.

PMID- 8565205
TI  - R325X mutation in exon 15 of the hydroxymethylbilane synthase gene identified in
      two Danish families with acute intermittent porphyria.

PMID- 8565206
TI  - Myoglobin/carbonic anhydrase III ratio: highly specific and sensitive early
      indicator for myocardial damage in acute myocardial infarction.

PMID- 8565207
TI  - When is a serum iron really a serum iron? A follow-up study on the status of iron
      measurements in serum.

PMID- 8565208
TI  - When is a "reference method" a "Reference Method"?

PMID- 8565209
TI  - Possible interference with calcipotriol on new IDS RIA for 1,25-dihydroxyvitamin
      D.

PMID- 8565210
TI  - More on antioxidant activity of resveratrol in red wine.

PMID- 8565211
TI  - Greater frequency of increased cardiac troponin T than increased cardiac troponin
      I in patients with chronic renal failure.

PMID- 8565212
TI  - Precision and accuracy of the Accu-Chek Advantage blood glucose monitoring system
      at high altitude.

PMID- 8565213
TI  - The scope and impact of thyroid disease.
AB  - Aspects of the incidence and demographics of common thyroid disorders in the US
      (and elsewhere, to a lesser extent) are reviewed. The impact of healthcare reform
      and the efforts of managed care organizations to impose cost-effective management
      for the diagnosis and treatment of thyroid disorders are bringing unusual
      pressures to bear on both clinical laboratories and practicing endocrinologists.
      I discuss the potential dangers of utilization of suboptimally focused diagnostic
      approaches and of the inefficiencies in clinical management by primary-care
      providers, who often lack sufficient expertise, as opposed to endocrinologists.
      More than dollars are at stake, and the suboptimal management of common thyroid
      disorders presents several significant risks. Finally, I propose a general
      blueprint for the ongoing development of a structure for continuing quality
      improvement of the laboratory and clinical diagnosis, treatment, and long-term
      follow-up of patients with thyroid disease.

PMID- 8565214
TI  - Preanalytical considerations in testing thyroid function.
AB  - Remarkable technical advances have permitted analytical measurement of
      thyrotropin (TSH) and estimates of free thyroxine (FT4) with precision, accuracy,
      and favorable economics. Combined with an increased appreciation of the key
      insights into the pituitary-thyroid relation, preanalytical considerations
      infrequently introduce confounding variables. In reviewing thyroid data,
      preanalytical considerations include physiological and specimen-based issues.
      Central to the improvement in thyroid assessment is the recognition that
      physiological individuals maintain their FT4 within narrow limits. When this
      deviates, there is a logarithmic response of the TSH concentration to the
      arithmetic shift in FT4. In effect, the TSH deviation magnifies the subtle shift
      in FT4. Artifact and other nonthyroid-related preanalytical considerations are
      infrequently the cause of nonconcordance when discrepancy occurs between the
      reported values for FT4 and TSH. When abnormalities of TSH and FT4 are
      encountered, the probability strongly favors a disease state rather than a
      preanalytical variable. Infrequent but real extrathyroidal pathophysiological
      states are increasingly recognized as a result of the reliable assessment of the
      pituitary-thyroid relation.

PMID- 8565215
TI  - Physiological variations in thyroid hormones: physiological and
      pathophysiological considerations.
AB  - Thyroid hormone production is regulated via pituitary thyrotropin (TSH)
      modulation of thyroxine (T4) prohormone secretion by the thyroid gland and
      regulation of active triiodothyronine (T3) production in peripheral tissues via
      metabolic events influencing activities of the iodothyronine monodeiodinase
      enzyme systems. Control at both levels is developmentally regulated and modified
      in serious nonthyroidal illness (trauma, infection, cancer, metabolic diseases).
      Racial and gender differences are of little significance except for the effects
      of placental estrogens and chorionic gonadotropin during pregnancy. There is a
      circadian rhythm of TSH secretion, with peak values at the onset of sleep and
      nadir concentrations during the afternoon hours. Peak and nadir concentrations
      differ by approximately +/- 50%. The effect on circulating T4 and T3
      concentrations is not significant because of the large size of the extrathyroidal
      T4 pool. In healthy subjects there is no significant impact of body weight,
      physical training, body habitus, posture, immobilization, exercise, or ambulatory
      status on thyroid function, and no significant geographic environmental
      variation. Nutrition also has a minimal impact except for variation in iodine
      intake. Subthreshold concentrations of iodine intake are associated with
      increased TSH secretion, goiter, increased thyroid iodine uptake, decreased T4
      production, an increased T3/T4 secretion ratio, and an increased ratio of
      circulating T3/T4 concentrations. Excessive iodine intake can block thyroid
      hormone biosynthesis by inhibiting the enzymes involved in the biosynthetic
      process, resulting in reduced T4 secretion, increased TSH concentrations, goiter,
      and hypothyroidism if the iodine excess is chronic.

PMID- 8565216
TI  - Chemiluminescent hybridization-ligation assays for delta F508 and delta I507
      cystic fibrosis mutations.
AB  - Chemiluminescent hybridization-ligation assays were devised to detect the delta
      F508 and delta I507 cystic fibrosis mutations in samples of human DNA that had
      been amplified by PCR. Two synthetic DNA oligomers were used in each assay. One
      of the oligomers was labeled with an acridinium ester and the other was
      immobilized on paramagnetic particles. The oligomers were hybridized to the
      samples and the target sequences discriminated by ligation with T4 or a
      thermostable DNA ligase. The performance of the assay was evaluated in a blind
      study of 30 samples. There was complete correspondence between the assignments
      based on the chemiluminescent assay and those made previously by gel
      electrophoresis, with one exception. The assignment of this discrepant sample by
      the chemiluminescent assay as a delta I507/normal heterozygote rather than a
      delta F508/normal heterozygote was confirmed by sequencing. The chemiluminescent
      hybridization-ligation assay provides a rapid and convenient means of
      discriminating DNA sequences differing by a single nucleotide.

PMID- 8565217
TI  - Current status and performance goals for serum thyrotropin (TSH) assays.
AB  - Current medical needs dictate that laboratories offer thyrotropin (TSH) assays
      that can reliably measure low TSH concentrations--a prerequisite for using the
      more cost-effective TSH-centered strategy currently recommended by the American
      Thyroid Association. This study reviews the functional performance of the TSH
      immunometric assay methods currently used in clinical practice. Methodological
      differences between methods, the rationale for using the 20% interassay CV as the
      functional sensitivity limit for patient reports, and both TSH-related and non
      TSH-related specificity problems are reviewed. We recommend that manufacturers
      and clinical laboratories use a clinically relevant standard protocol for
      functional sensitivity assessments. In this protocol, human serum pools are
      analyzed in random order 10 or more times across a clinically realistic time span
      (which approximates to 6-8 weeks for TSH measurements used in an outpatient
      setting). Laboratories should independently establish and periodically check
      their functional sensitivity by the standard protocol and enlist the
      manufacturer's help to accomplish this if necessary. Manufacturers should (a)
      develop promotional material that realistically projects the assay's functional
      sensitivity expected in a clinical laboratory setting, (b) ensure that new
      clinical laboratory users achieve the projected functional sensitivity target
      when using the standard protocol, and (c) focus on the typical functional
      sensitivity obtained by clinical laboratory users rather than the assay's
      "generation" achieved under ideal conditions. If manufacturers and laboratories
      collaborate to solve the sensitivity and specificity problems discussed here,
      clinical laboratories should be better able to consistently deliver reliable
      serum TSH measurements across the full range of TSH concentrations encountered in
      clinical practice.

PMID- 8565218
TI  - Analytical performance of free and total thyroxine assays.
AB  - Excessive bias and imprecision are major analytical problems associated with some
      assays for free and total thyroxine (T4). Bias in free T4 methods is largely
      proportional to variations in serum T4 binding. In direct methods, this is
      attributable to requirements for substantial quantities of protein-bound T4 to
      replace analytical losses of free T4. In some total T4 methods, bias is inversely
      proportional to the amount of serum T4 binding and is attributable to the
      incomplete release of serum protein-bound T4. In others, bias is fixed and
      attributable to inaccurate calibration. Manufacturers should report the bias in
      their methods. Calibrations should be standardized. Imprecision varies widely
      among methods, but is generally less for total T4 methods than for free T4
      methods. A consensus on quantitative analytical performance goals for free and
      total T4 methods would be helpful. Here, performance goals are proposed, based in
      part on the best achievements of current methods.

PMID- 8565219
TI  - Clinical usage recommendations and analytic performance goals for total and free
      triiodothyronine measurements.
AB  - The major clinical role for total triiodothyronine (TT3) and (or) free T3 (FT3)
      is the assessment of hyperthyroidism in patients with suppressed sensitive
      thyrotropin (sTSH) concentrations. The assays are particularly important in
      hyperthyroid patients with normal free thyroxine (FT4) concentrations to assess
      potential T3 thyrotoxicosis. Other specialized uses for T3 and FT3 measurements
      are monitoring thyroid hormone replacement therapy, the evaluation of amiodarone
      induced thyrotoxicosis, and predicting outcome of antithyroid drug therapy in
      patients with Graves hyperthyroidism. The roles of these tests in assessing heart
      function in cardiopulmonary bypass surgery, evaluation of patients with
      neuropsychiatric disorders, and monitoring of patients on anticonvulsant therapy
      are not well defined. These assays are not recommended for diagnosis of
      hypothyroidism. Analytic recommendations include CV < 5.2% for T3 and < 3.8% for
      FT3; < 0.2% cross-reactivity with L-T4; and < 1.0% cross-reactivity with D-T4, D
      T3, and reverse T3.

PMID- 8565220
TI  - Analytical and clinical performance goals for testing autoantibodies to
      thyroperoxidase, thyroglobulin, and thyrotropin receptor.
AB  - Methods for measuring thyroid autoantibodies--to thyroperoxidase (TPOAb),
      thyroglobulin (TgAb), and thyrotropin receptor (TRAb)--have improved over the
      last decade, but increasingly, accurate and sensitive methods are needed for
      identifying patients with autoimmune thyroid diseases and individuals at high
      risk for onset of thyroid autoimmunity. With the increased quality requirements
      for these methods, it becomes more important to look at the functional
      sensitivities and precision profiles of the various methods. International
      standardization in this field is also needed. Because most sera containing human
      thyroid autoantibodies display a variety of antigen-specific immunoglobulins of
      different classes and subclasses with different affinity and avidity in their
      epitope reaction, investigators must decide whether the autoantibodies should be
      quantified in terms of immunoglobulin content, antigen/epitope reactivity, or
      binding capacity. Until these problems are solved, the best means for
      standardization are the Medical Research Council calibrators for TPOAb and TgAb,
      whereas no standardization exists for TRAb.

PMID- 8565221
TI  - Current status and performance goals for serum thyroglobulin assays.
AB  - Serum thyroglobulin (Tg) measurements are used as a tumor marker for monitoring
      patients with differentiated thyroid carcinoma. The clinical utility of six
      different Tg methods [RIA or immunometric assay (IMA)] currently used in Europe
      and the US was evaluated, with focus on methodologic standardization,
      sensitivity, interassay precision across the typical clinical monitoring interval
      (6 to 12 months), "hook" effects (IMA methods), and Tg autoantibody interference.
      The methods evaluated were: DYNOtest Tg (Henning), OptiQuant Tg (Kronus), SELco
      Tg (Medipan), Thyroglobulin IRMA (Pasteur), Nichols Chemiluminescent ICMA
      (Corning Nichols), and an RIA developed by us (USC Endocrine Services
      Laboratory). The clinical impact of the current methodologic problems on the use
      of serum Tg measurements is reviewed. Optimal performance goals are recommended
      for manufacturers developing and laboratories and physicians selecting a serum Tg
      method to use for serial long-term monitoring of thyroid cancer patients.

PMID- 8565223
TI  - Modern concepts of primary thyroid gland failure.
AB  - Primary thyroid gland failure is a common medical disorder occurring in mild or
      severe forms in 10% to 15% of our population. Symptoms may be classical and easy
      to recognize or very subtle, escaping clinical detection. This disorder is more
      common in females and increases with advancing age. The most important diagnostic
      test is measurement of the serum thyrotropin (TSH) concentration, which will
      increase above the normal range in both mild and severe cases. Most clinical
      effects of thyroid hormone deficiency can be explained by the "nuclear thyroid
      hormone hypothesis," which states that thyroid hormones act predominantly by
      effecting the transcription of key genes in affected tissues. Therapy of
      hypothyroidism is easy, inexpensive, and precise, involving pure L-thyroxine and
      measuring dose requirements and efficacy by monitoring serum TSH concentrations.

PMID- 8565222
TI  - Evaluation of thyroid status in patients with thyrotoxicosis.
AB  - The generic term thyrotoxicosis defines the clinical syndrome of hypermetabolism
      associated with excess amounts of circulating free thyroxine (T4) and (or)
      triiodothyronine (T3) concentrations, irrespective of the source of the excess
      hormones. The term hyperthyroidism is reserved for those patients with
      thyrotoxicosis caused by increased synthesis and secretion of thyroid hormones
      from the gland due either to thyroid stimulators in the blood or to autonomously
      functioning thyroid nodules and is almost always associated with an increased
      radioactive iodine uptake (RAIU) by the thyroid. Another major cause of
      thyrotoxicosis is increased release of thyroid hormone from the gland, not
      associated with increased synthesis, caused by inflammatory changes, and always
      associated with a low thyroid RAIU. The most common miscellaneous cause of
      thyrotoxicosis is the exogenous ingestion of excess thyroid hormone, associated
      with a low thyroid RAIU. The serum concentration of thyrotropin (TSH) is low in
      all causes of thyrotoxicosis, except for TSH-secreting pituitary tumors and
      selective pituitary resistance to thyroid hormones. Anti-thyroglobulin and anti
      thyroid peroxidase antibodies are present in patients with autoimmune thyroid
      disease, and serum thyroglobulin is increased in all patients with thyrotoxicosis
      except those with thyrotoxicosis facticia. A decreased serum TSH and normal
      concentrations of serum free T4 and T3 define the syndrome of subclinical
      thyrotoxicosis.

PMID- 8565224
TI  - Optimal laboratory testing for diagnosis and monitoring of thyroid nodules,
      goiter, and thyroid cancer.
AB  - Optimal use of laboratory tests to diagnose and monitor patients with goiter,
      thyroid nodules, or thyroid cancer requires an appreciation of the
      pathophysiologic factors implicated in thyroid hyperplasia and neoplasia: growth
      factors (especially thyrotropin, TSH), growth-stimulating immunoglobulins,
      activating mutations of the TSH receptor, and other oncogenic transformations. In
      patients with diffuse goiter and thyroid nodules, serum TSH measurement in a
      highly sensitive assay excludes both primary hypothyroidism and common causes of
      thyrotoxicosis. In selected patients, screening for anti-thyroid peroxidase with
      or without anti-thyroglobulin antibodies can confirm the diagnosis of autoimmune
      thyroiditis. Serum calcitonin measurement is appropriate only when medullary
      thyroid carcinoma (MTC) is clinically suspected. Laboratory testing is essential
      in management of thyroid carcinoma patients after primary surgical therapy. Serum
      TSH measurement is vital to ensure that thyroxine replacement and TSH suppression
      are adequate in treatment of epithelial cancers. Serial monitoring of serum
      thyroglobulin (Tg) can detect tumor recurrence and quantify tumor burden.
      Interpretation of serum Tg results requires an appreciation of certain technical
      considerations (e.g., anti-Tg antibody interference) and the patient's concurrent
      TSH status. Periodic serum Tg measurements and 131I scans are complementary
      monitoring techniques. Serum calcitonin measurement and screening for ret
      protooncogene mutations are both valuable for identifying individuals with MTC.

PMID- 8565225
TI  - Guidelines for diagnosis and monitoring of thyroid disease: nonthyroidal illness.
AB  - On the basis of low specificity, poor positive predictive value, and cost, there
      is at present no basis for routine assessment of thyroid function in acutely
      hospitalized patients, unless clinical features suggest the possibility of
      thyroid dysfunction, or a patient's background increases the likelihood of
      thyroid dysfunction. When used in severely ill patients, estimates of both
      thyroxine (T4) and thyrotropin (TSH) show a high prevalence of abnormal results,
      but lack specificity and have poor positive predictive value for true thyroid
      disease. When thyroid function is tested in the critically ill, the positive
      predictive value for true thyroid disease of both free T4 and TSH measurements
      could be improved by using wider reference intervals than for unselected
      populations. The knowledge of nonspecific disease-related abnormalities of
      triiodothyronine, T4, and TSH is not currently likely to yield useful prognostic
      information or to alter management for individual patients. Thyroid testing
      should be readily available for any acutely ill patient with any clinical
      features that suggest thyroid dysfunction, and for groups at increased risk of
      thyroid dysfunction. An initial abnormal result for either TSH or free T4
      estimate should be followed by combined analysis of free T4 and TSH with the best
      available methodology. Diagnosis of thyroid dysfunction should be based on the T4
      TSH relation rather than either value alone. Persistence of an apparent
      diagnostic abnormality should be confirmed before therapy is commenced.

PMID- 8565226
TI  - Monoclonal antibodies against a C-terminal peptide of human brain
      acetylcholinesterase distinguish between erythrocyte and brain
      acetylcholinesterases.
AB  - Monoclonal antibodies (mAbs) were raised against a peptide of the 10 C-terminal
      amino acids of human brain acetylcholinesterase (AChE): H-Tyr-Ser-Lys-Gln-Asp-Arg
      Cys-Ser-Asp-Leu-OH. Two positive clones (mAbs 190-1 and 190-2) were selected and
      tested for their ability to distinguish between mammalian brain and erythrocyte
      AChEs. In a solid-phase enzyme antigen immunoassay as well as by Western- and dot
      blot analysis, both antibodies showed clear binding to AChE from human and bovine
      brain but not to AChE from erythrocytes. MAbs 190-1 and 190-2 reacted with
      neither AChE from electric eel nor butyrylcholinesterase from human serum. Both
      antibodies were used in a quantitative assay for AChE in amniotic fluids, where
      AChE activity could be found only in samples from open neural tube-defect
      pregnancies, but not in fluids from normal pregnancies or in artificially blood
      contaminated samples.

PMID- 8565227
TI  - Fatty acid ethyl ester synthase, an enzyme for nonoxidative ethanol metabolism,
      is present in serum after liver and pancreatic injury.
AB  - Fatty acid ethyl esters (FAEE), esterification products of ethanol and fatty
      acids, have been implicated as mediators of ethanol-induced organ damage. Because
      cytosolic enzymes such as aspartate aminotransferase, lipase, and amylase appear
      in the blood after liver or pancreatic damage, we hypothesized that FAEE
      synthase, which is both cytosolic and membrane bound, is also released into the
      blood of patients with liver or pancreatic disease. We used a method involving
      thin-layer chromatography coupled with gas chromatography-mass spectrometry to
      reliably identify and quantify FAEE. In this study, we demonstrated that patients
      with liver or pancreatic disease release FAEE synthase into their plasma in
      amounts proportional to the amount of aspartate aminotransferase (r = 0.78),
      amylase (r = 0.65), and lipase (r = 0.63). These data indicate that liver and
      pancreatic damage results in release of FAEE synthase into the blood. The
      presence of FAEE synthase in plasma permits nonoxidative ethanol metabolism in
      the plasma.

PMID- 8565228
TI  - Multicenter evaluation of the Abbott IMx CA 15-3 assay.
AB  - We describe a new fully automated procedure for the quantitative measurement of
      CA 15-3: the microparticle enzyme immunoassay (MEIA) technology developed by
      Abbott Labs. for the IMx automated immunoassay analyzer. The new IMx CA 15-3 test
      uses two mouse monoclonal antibodies, 115D8 and DF3. The test has a dynamic range
      to 250 kilounits/L and a minimal detectable dose of CA 15-3 < 0.2 kilounits/L. On
      dilution, linearity is excellent, with recoveries ranging from 94% to 101%.
      Studies were conducted at four sites to evaluate the performance characteristics
      of this assay. The intra- and interassay CVs were < 4.7% and < 5.6%,
      respectively, and showed a between-laboratory CV < 5.9%. Test results of the
      Abbott IMx CA 15-3 (y) were correlated with those obtained with the Centocor CA
      15-3 RIA (x), a solid-phase heterologous RIA. Linear regression analysis on
      results for 1973 samples yielded: y = 0.97x - 2.09 (r = 0.9899, Sy/x = 22.2,
      range 1-4089 kilounits/L).

PMID- 8565229
TI  - Enzyme immunoassay validation for qualitative detection of cocaine in sweat.
AB  - A solid-phase enzyme immunoassay (EIA) involving microtiter plates was modified
      for analysis of cocaine in sweat. Sweat was collected with the PharmChek sweat
      patch and drugs were eluted from the collection pad of the patch. The sweat
      contained primarily parent cocaine. The assay was determined to have cross
      reactivity for cocaine of 102% relative to 100% for the benzoylecgonine (BE)
      calibrators and for cocaethylene of 148%. The optimum cutoff concentration for
      this modified assay, determined by receiver-operating characteristic curve
      analysis, was 10 micrograms/L cocaine or BE equivalents. At this concentration
      the assay had 94.5% sensitivity and 99.1% specificity vs gas chromatography-mass
      spectrometry (GC-MS) as an acceptable indicator of the true clinical state. The
      positive predictive value at a prevalence of 50% was 99%. Threshold analysis for
      positives suggested that the 95% confidence interval for a positive result by the
      EIA was between 12.5 and 15 micrograms/L and that quality-control samples at 5
      and 15 micrograms/L could be run with each batch to certify the precision around
      the cutoff. All positive samples must be confirmed by GC-MS. The sensitivity and
      specificity of the overall analysis system (immunoassay screen and GC-MS
      confirmation) was 86% and 97%, with known cocaine dosing of volunteers as the
      acceptable indicator of the true clinical state.

PMID- 8565230
TI  - Evaluation of clinical assays for measuring high-dose methotrexate in plasma.
AB  - Four routine assays commonly used for monitoring plasma methotrexate (MTX) during
      high-dose therapy were validated by HPLC as the comparison method. MTX and its
      main metabolite, 7-hydroxymethotrexate (7-OHMTX), were analyzed by HPLC with
      postcolumn derivatization and fluorometric detection. About 200 clinical plasma
      samples from 13 children with acute lymphoblastic leukemia who received 5-8 g/m2
      MTX as 24-h infusions were analyzed. The fraction of measured concentrations of
      MTX that were within 75-125% of the values obtained by HPLC were 64.5% for enzyme
      inhibition assay, 56.4% for fluorescence polarization immunoassay with polyclonal
      antibodies (FPIA1; Abbott), 58.9% for FPIA2 (with monoclonal antibodies; Abbott),
      and 46.4% for enzyme-multiplied immunoassay (Emit; Syva). All nonchromatographic
      procedures were subject to interferences from MTX plasma metabolites or
      endogenous substances. The interference from 7-OHMTX was, however, somewhat less
      pronounced for FPIA2 (monoclonal) than for FPIA1 (polyclonal).

PMID- 8565231
TI  - Nighttime dosing assures postdistribution sampling for therapeutic drug
      monitoring of digoxin.
AB  - To study the appropriateness of phlebotomy for digoxin therapeutic drug
      monitoring (TDM) in outpatients, we conducted a retrospective chart review, a
      computer search of all previous TDM testing, and a questionnaire of all
      outpatients (n = 86) who had serum digoxin determinations between April 10 and
      April 28, 1992 (585 tests). In patients who took digoxin at the same time daily
      (40 patients, 300 tests), 52% of tests were performed on inappropriate samples
      drawn within 6 h of the last dose. No patient who took digoxin after 1700 had
      inappropriate tests. Phlebotomy for serum digoxin determinations before
      distribution of digoxin is complete is a common problem in outpatients, leading
      to clinically uninterpretable test results. Postdistribution sampling can be
      assured by nighttime dosing, and this recommendation has been implemented at our
      hospital.

PMID- 8565232
TI  - Evaluation of a fully automated end-tidal carbon monoxide instrument for breath
      analysis.
AB  - We evaluated a novel, portable breath sampler/CO-quantifying instrument [Baby's
      Breath Carbon Monoxide Analyzer (BB); Natus Medical], developed for use at the
      bedside or with gas samples collected into bags. Bench tests demonstrated that
      the CO measurements were linear, accurate, and precise when compared with gas
      chromatography (GC) results. In vivo tests (n = 30) performed with adults showed
      excellent correlation between end-tidal breath CO measurements (ETCO) corrected
      for inhaled CO (ETCOc) as determined by BB and GC. Breath sampling efficiency was
      96%. ETCOc measurements and blood carboxyhemoglobin fractions (% of total
      hemoglobin) corrected for inhaled CO (COHbc) correlated strongly: COHbc = 0.25
      ETCOc--0.01 microL/L CO (r2 = 0.97, Sy/x = 0.47, SE slope = 0.01, n = 30). The
      imprecision, assessed by the mean of the population's CV for triplicate
      determinations, was 11%. Measurements with healthy and hemolytic term newborns
      showed that ETCOc values of > 3 microL/L correlated with known hemolytic
      conditions. We conclude that this instrument is clinically reliable and can be
      used to noninvasively measure ETCO in neonates and adults.

PMID- 8565233
TI  - Identification and quantification of hemoglobins A, F, S, and C by automated
      chromatography.
AB  - The Bio-Rad Variant Hemoglobin Testing System is an automated HPLC analyzer
      marketed with a Beta-thalassemia Short Program to quantify hemoglobins (Hbs) F
      and A2 and assist in detecting Hbs A, S, C, D, and E. We evaluated this system to
      replace several traditional methods for Hb in our hospital laboratory. Analytical
      performance relevant to quantifying Hbs A, S, C, and F was assessed with blood
      samples obtained from our local patient population. Studies of precision (CVs <
      3%) and analytical limits (% of total Hb) of Hbs A (2-86%), F (1-89%), S (5-90%),
      and C (3-92%) demonstrated results comparable with or exceeding those of
      traditional methods. Results for patients' samples (n) for Hbs A (107), F (157),
      S (128), and C (27) correlated well (r > 0.93) with results by traditional
      methods. The satisfactory performance and efficiency led us to implement this
      system for routine quantification of clinically significant Hbs.

PMID- 8565234
TI  - The profession in an uncertain environment.

PMID- 8565235
TI  - Blood glutathione concentrations in a large-scale human study.
AB  - Little is known about the variability of blood glutathione (GSH) in human
      subjects. Thus, we wanted to develop and validate a rapid method for measuring
      GSH concentrations in whole blood and apply this method to ascertain the
      variation of GSH in a large-scale study of free-living adults. The assay was
      highly sensitive (detection limit < 5 pmol) and precise, with an interassay
      variation of 2.3% and a sampling variation of 3.6%. Applying this method to
      screen 715 adults, we observed a threefold range of GSH concentrations, with a
      mean of 1.02 mmol/L and CV of 17%. GSH concentrations were 8-10% greater in
      smokers than in nonsmokers (P < 0.001). Although we observed no sex differences
      for GSH, GSH/hemoglobin ratios were 8-18% greater in women < 55 years old than in
      older subjects (P < 0.05). The results presented here validate the use of this
      method for large-scale human studies and provide information on the variation and
      normal values of blood GSH in adults.

PMID- 8565236
TI  - Automation of molecular diagnostics.

PMID- 8565237
TI  - Rapid and simultaneous quantification of rhamnose, mannitol, and lactulose in
      urine by HPLC for estimating intestinal permeability in pediatric practice.
AB  - Determination of intestinal permeability by measuring nonmetabolized sugars has
      been used to assess the integrity of intestinal mucosa. We have developed and
      validated a modified HPLC method for determining the concentration of L-rhamnose,
      mannitol, and lactulose in urine, using an amine-modified silica column and
      refractive index detection. Probe sugars are simultaneously resolved within 18
      min. The calibration curve for each sugar is linear to 20 mmol/L. The minimum
      detectable concentration of lactulose is 0.05 mmol/L. Recovery of probe sugars is
      between 99.3% and 105.1%. Overall precision (CV) of estimation of probe sugars
      ranges from 4.2% to 6.5%. In 14 urine samples from healthy children who ingested
      the test solution containing 1 g of L-rhamnose, 1 g of mannitol, and 5 g of
      lactulose, the 5-h urinary excretion ratios of lactulose/rhamnose and
      lactulose/mannitol were 0.047 +/- 0.018 and 0.021 +/- 0.010 (mean +/- SD),
      respectively. This method presents a rapid, convenient, and practical technique
      for determining intestinal permeability in clinical pediatric practice.

PMID- 8565238
TI  - Marked interference of hyperglycemia in measurements of mean (red) cell volume by
      Technicon H analyzers.
AB  - Severe hyperglycemia can result in falsely high results for mean cell
      (erythrocyte) volume (MCV), which will also cause false results for erythrocyte
      indices calculated on the basis of MCV. Falsely high MCV results were obtained
      with the Technicon H1 and H2 analyzers and (to a lesser extent) with the Coulter
      T660. The H analyzers were more susceptible to this interference than was the
      Coulter T660. This difference in sensitivity of MCV to hyperglycemia can be
      explained by the use of sodium dodecyl sulfate in the Technicon erythrocyte
      diluent and by differences in incubation times. In severe hyperglycemia, results
      for MCV, mean cell hemoglobin concentration, and hematocrit obtained from
      electronic cell counters, especially Technicon H systems, are unreliable.

PMID- 8565239
TI  - Logical observation identifier names and codes (LOINC) database: a public use set
      of codes and names for electronic reporting of clinical laboratory test results.
AB  - Many laboratories use electronic message standards to transmit results to their
      clients. If all laboratories used the same "universal" set of test identifiers,
      electronic transmission of results would be greatly simplified. The Logical
      Observation Identifier Names and Codes (LOINC) database aims to be such a code
      system, covering at least 98% of the average laboratory's tests. The LOINC
      database should be of interest to hospitals, clinical laboratories, doctors'
      offices, state health departments, governmental healthcare providers, third-party
      payors, organizations involved in clinical trials, and quality assurance and
      utilization reviewers. The fifth release of the LOINC database, containing codes,
      names, and synonyms for approximately 6300 test observations, is now available on
      the Internet for public use. Here we describe the LOINC database, the methods
      used to produce it, and how it may be obtained.

PMID- 8565241
TI  - The changing environment for the practice of clinical chemistry. AACC Task Force
      on the Changing Practice Environment.

PMID- 8565240
TI  - Strand displacement amplification (SDA) and transient-state fluorescence
      polarization detection of Mycobacterium tuberculosis DNA.
AB  - Strand displacement amplification (SDA) is an isothermal, in vitro method of
      amplifying a DNA sequence for diagnostic purposes. We have combined SDA with
      fluorescence polarization detection in a closed, homogeneous format. A
      fluorescently labeled oligodeoxynucleotide detector probe hybridizes to the
      amplification product that increases in concentration during SDA. The single- to
      double-stranded conversion of the probe is accompanied by an increase in
      fluorescence polarization values, which can be measured in real-time without
      physical manipulation of the sample. The probe was labeled with the near-infrared
      dye La Jolla Blue, and fluorescence polarization was measured on a transient
      state fluorometer. We have applied this homogeneous SDA/detection system to a
      target DNA sequence specific for Mycobacterium tuberculosis DNA.

PMID- 8565242
TI  - The future of clinical chemistry and its role in healthcare: a report of the
      Athena Society.
AB  - Given the omnipresent cost-containment environment in which clinical chemists now
      work, they must adapt to a host of changed conditions and new pressures. Much of
      the onus of adapting is on the individual who must assume a different attitude to
      his or her work. The American Association for Clinical Chemistry can, and should,
      take a leadership role in developing a new type of laboratory director by working
      with other professional organizations in the clinical laboratory field to create
      training programs and retraining programs for existing clinical laboratory
      scientists, which will equip them for broader scientific and managerial
      responsibilities than hitherto. AACC needs to develop alliances with its sister
      organizations so that the common issues are addressed collectively rather than
      competitively. The scope of clinical chemistry must expand into areas other than
      traditional clinical chemistry, e.g., microbiology, immunology, certain aspects
      of hematology (including coagulation), and even aspects of blood banking. The
      former clinical chemist needs to become a clinical laboratory scientist and
      promote him- or herself as having cross-disciplinary expertise in analytical
      techniques and automation, which are the common threads linking all branches of
      clinical laboratory science.

PMID- 8565243
TI  - Arterial hypertension causing leg ulcers.
AB  - We report clinical and histological features of 16 consecutive patients with
      hypertensive leg ulcers. The lumen/wall ratio in arterioles at the edges of these
      hypertensive leg ulcers was compared with that in other types of chronic leg
      ulcers and was found to be significantly reduced (P < 0.001). Additional
      conditions such as venous hypertension or main vessel arterial disease
      contributed. Nineteen of 22 ulcers were completely healed after a mean of 4.9
      months. Recognition of this condition enables correct treatment choice, which
      usually involves excision and grafting, and early healing.

PMID- 8565244
TI  - Analyses of T-cell receptor beta-chain genes by Southern blotting in known and
      suspected cutaneous T-cell lymphoma. A study of 67 samples from 32 patients.
AB  - In this study we have investigated the configuration of the T-cell receptor (TCR)
      beta-chain genes in benign cutaneous conditions (n = 5) and known (n = 22) or
      suspected (n = 5) cutaneous T-cell lymphoma (CTCL). Sequential biopsies from
      skin, lymph node, blood and/or bone marrow were available in 12 cases of the 22
      confirmed CTCL, and a total of 67 samples were analysed. In the benign
      conditions, clonal rearrangements of the TCR beta-chain genes were seen in
      neither skin nor blood samples. In contrast, in CTCL clonal rearrangements were
      detected in all skin samples from plaque or tumour lesions of mycosis fungoides.
      Clonal TCR rearrangements were also present in skin and blood samples from two
      patients with Sezary's syndrome, and in skin and blood samples from three of five
      patients with clinically suspected CTCL. In 10 patients with large cell
      lymphomas, clonal rearrangements were detected in skin samples in half of the
      cases. In the remaining patients, clonal TCR rearrangements could not be detected
      in the skin, but only in the blood and/or bone marrow specimens. Results from the
      analyses of sequential biopsies showed identical patterns of rearrangement in 11
      patients. In the remaining patient, the pattern of rearrangement differed between
      skin and lymph node. These data confirm and extend previous reports and indicate
      that analysis of TCR beta-chain genes by Southern blotting forms a useful
      supplement to other methods for the diagnosis of known and suspected CTCL. They
      also emphasize the importance of studying not only skin, but also extracutaneous
      sites.

PMID- 8565245
TI  - Class II MHC typing in pemphigoid gestationis.
AB  - Pemphigoid gestationis (PG) is a rare, autoimmune skin disease associated with
      pregnancy or the immediate post-partum period, previously shown to be associated
      with the HLA class II antigens DR3 and DR4. Advances in molecular analytical
      techniques now allow the identification of HLA alleles previously difficult to
      define by serological assays. Unsuspected polymorphism within the HLA-DR3 and DR4
      classes can, therefore, be identified. The aim of our study was to apply these
      newer techniques to the question of genetic predisposition in PG by re-evaluating
      the association with DR3 and by studying a possible link with DQ. We have
      investigated by restriction fragment length polymorphism, the DQA, and by
      sequence specified oligonucleotide probing the DQB and DRB1 (HLA DR)
      specificities of 41 women with immunofluorescence-confirmed PG. The principal
      finding of this study is that there is an association between PG and DRB1*0301
      (DR3) and DRB1*0401/040X (DR4). Although there is also an increase (P = 0.06) in
      the concurrent presence of both antigens, this appears to be due to the
      association with either antigen alone. We also found an increase in the frequency
      of DQA1*2 (P = 0.016 vs. control) and a decrease in frequency of DQB1*0201 (P =
      0.022 vs. controls) and DQB1*0602 (P = 0.026 vs. controls).

PMID- 8565246
TI  - Oral cyclosporin A restores hair growth in the DEBR rat model for alopecia
      areata.
AB  - The Dundee experimental bald rat (DEBR) undergoes hair loss associated with the
      development of peri- and intrafollicular mononuclear cell infiltrates, as occurs
      in human alopecia areata. We studied the effect of orally administered
      cyclosporin A (10 mg/kg; 5 days/week for 7 weeks) on established lesional DEBR
      rats displaying extensive areas of hair loss. New hairs appeared after 10 days
      and there was simultaneous regrowth of hair over the whole body with restoration
      of a full pelt by 5 weeks. Semiquantitative histological examination of flank
      skin biopsies revealed early reduction of the cellular infiltrate associated with
      conversion of dystrophic anagen follicles to normal, hair-producing follicles.
      These results confirm the value of the DEBR model of alopecia areata in
      evaluating existing and new therapies for this disease in humans.

PMID- 8565247
TI  - Survey of quality issues in dermatology service contracts. Audit Subcommittee of
      the British Association of Dermatologists.
AB  - Most hospitals now have acquired trust status and managers have started the
      process of setting contracts with purchasers. In order to assess quality content
      of contracts for dermatology services, a survey was performed on behalf of the
      British Association of Dermatologists' (BAD) Audit Subcommittee. A letter was
      sent to 278 consultant members of the BAD, requesting a copy of their contract:
      171 (62%) replies were received. Seventy-four consultants had formal contracts
      with purchasers, but only 25 (34%) of these had been involved in contract
      preparation. Several consultants were unsure whether formal contracts existed and
      many had difficulty in obtaining the documents. The 20 contracts received were
      highly variable, with a median of 13 (range 0-89) quality clauses per contract.
      These mostly related to the process of care, particularly waiting times and
      communication with general practitioners (GPs). Sometimes the structure for
      delivering care was specified, but only occasionally were outcome measures
      mentioned. The specified maximum waiting time for a new patient appointment
      ranged between 4 and 30 weeks (median 13). GPs were to be sent out-patient
      letters within 3-10 days (median 10) of patient attendance. Following in-patient
      care a notification was to be sent within 1-3 days (median 2) of discharge and a
      full summary within 7-21 days (median 12). A requirement for patient satisfaction
      surveys was included in only six contracts. Greater involvement of consultant
      dermatologists in setting contracts with purchasers should lead to the inclusion
      of more consistent and appropriate quality clauses.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8565248
TI  - Follow-up of adult patients with atopic eczema treated with Chinese herbal
      therapy for 1 year.
AB  - Adult patients with severe atopic eczema who had completed a double-blind placebo
      controlled crossover trial of a specific formulation of Chinese herbal therapy
      were offered continued therapy for 1 year. Of 31 patients who completed the
      original placebo-controlled study and after a washout period and 2 months of
      further treatment, 17 continued treatment (group 1), 11 chose not to continue
      treatment (group 2), one was lost to follow-up and two patients originally in
      group 1 decided to stop treatment and became pregnant. At the end of the year, 12
      of the patients in group 1 had greater than 90% reduction and the remaining five
      had greater than 60% reduction in clinical scores compared with baseline values.
      Clinical scores of patients in group 2 gradually deteriorated so that by the end
      of the year the difference between groups 1 and 2 was highly significant (P =
      0.005 and P = 0.002 for erythema and surface damage, respectively). At the end of
      the year no patient in group 1 felt able to discontinue treatment permanently,
      but eight patients were on an alternate-day regimen by 6 months and remained on
      this regimen until the end of the year, and seven were able to control their
      eczema with a 1 in every 3 day treatment by the end of the year. The remaining
      two patients continued on daily treatments. Toxicology screening revealed no
      abnormalities in either full blood counts or biochemical parameters in any
      patient on continued treatment. Improvement in disease was not associated with
      any significant change in serum IgE level or peripheral blood lymphocyte
      subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8565249
TI  - Partial lentiginosis.
AB  - A 14-year-old girl with partial unilateral lentiginosis affecting the left side
      of the neck, left shoulder and left upper arm is described. She also had a
      further patch of multiple lentigines over the right side of the face.

PMID- 8565250
TI  - Allergic airborne contact dermatitis from essential oils used in aromatherapy.
AB  - Contact allergy to various essential oils used in aromatherapy was demonstrated
      on patch testing in a 53-year-old patient suffering from relapsing eczema
      resistant to therapy on various uncovered parts of the skin, in particular the
      scalp, neck and hands. Sensitization was due to previous exposure to lavender,
      jasmine and rosewood. Laurel, eucalyptus and pomerance also produced positive
      tests, although there was no hint of previous exposure. A diagnosis of allergic
      airborne contact dermatitis was thus established. On topical and systemic
      glucocorticoid treatment (peroral methylprednisolone at an initial dose of 60
      mg/day) the skin lesions eventually resolved. Due to persistence of the volatile
      essential oils in the patient's home after a year-long use of aroma lamps,
      complete renewal of the interior of the patient's flat was considered essential.
      Due to changing self-medication habits, with increasing orientation to 'natural'
      modes of treatment, increasing numbers of such sensitizations might be on the
      horizon.

PMID- 8565251
TI  - Ranitidine-induced photosensitivity.
AB  - We report the case of a 72-year-old male patient who developed a florid
      photosensitive eruption while on ranitidine therapy. Ultraviolet A sensitivity
      was detected by irradiation monochromator testing, suggesting drug-induced
      photosensitivity. Ranitidine was concluded to be the cause of his
      photosensitivity since the eruption resolved and the phototest abnormalities
      returned to normal following cessation of therapy. Similar cases have been
      reported to the Committee on Safety of Medicines but not published.

PMID- 8565252
TI  - Improvement of scleredema associated with IgA multiple myeloma after
      chemotherapy.
AB  - The presence of a monoclonal gammopathy in patients with chronic scleredema is a
      recently described, unusual association of unknown significance. There have been
      very occasional reports of multiple myeloma in such patients. We now report a
      patient with long-standing scleredema who developed an IgA-kappa multiple
      myeloma. Once chemotherapy for the myeloproliferative disorder was instituted,
      scleredema improved significantly, suggesting a pathogenetic link between the two
      conditions.

PMID- 8565253
TI  - Milia restricted to the eyelids.

PMID- 8565254
TI  - Dapsone-induced motor peripheral neuropathy in pemphigus foliaceus.
AB  - We describe a case of pemphigus foliaceus complicated by dapsone-induced motor
      peripheral neuropathy. This idiosyncratic dapsone side-effect, which is rare
      other than in leprosy patients, was noteworthy for both its rapid onset,
      occurring within a month of commencing treatment, and its profound and prolonged
      nature.

PMID- 8565255
TI  - Spontaneous improvement of scleromyxoedema.

PMID- 8565256
TI  - Cutaneous T-cell lymphoma presenting as papuloerythroderma--a case and review of
      the literature.
AB  - Papuloerythroderma has been described as a distinct clinical entity. It is
      characterized by pruritus, red flat-topped papules with skin crease sparing,
      blood eosinophilia and lymphopenia. It has been described almost exclusively in
      elderly men. We report a case of cutaneous T-cell lymphoma which, at
      presentation, was indistinguishable from papuloerythroderma, in a 79-year-old
      male. An excellent clinical response to low dose oral corticosteroids and
      photochemotherapy was observed. There have only been two previous reports linking
      papuloerythroderma with T-cell lymphoma. This patient is in keeping with the two
      previously reported cases and would support the view that papuloerythroderma may
      predispose to, or in fact represent, an early form of cutaneous T-cell lymphoma.

PMID- 8565257
TI  - Dermatomyositis treated with high-dose intravenous immunoglobulins and associated
      with panniculitis.
AB  - Polymyositis and dermatomyositis are idiopathic inflammatory myopathies
      characterized by subacute symmetrical weakness of proximal limb and trunk
      muscles. Dermatomyositis is distinguished from polymyositis by the presence of
      rash. We describe an adult patient with treatment-resistant childhood-type
      dermatomyositis who made a good response to high dose intravenous
      immunoglobulins. Additionally, there was evidence of panniculitis which is an
      unusual histopathological finding in dermatomyositis.

PMID- 8565258
TI  - Neutrophilic dermatosis in association with rheumatoid arthritis.
AB  - Extra-articular involvement of the skin in patients with rheumatoid arthritis is
      not uncommon. A patient with this condition is reported who developed an unusual
      cutaneous eruption associated with systemic upset. Skin biopsy showed a dense
      dermal neutrophilic infiltrate and after treatment with standard
      immunosuppressive agents had failed he responded to dapsone. The rash recurred on
      withdrawal of the dapsone but has responded to sulphamethoxypyridamine. It is
      proposed that this condition is a rare but specific entity of unknown cause
      associated with rheumatoid arthritis.

PMID- 8565259
TI  - Squamous carcinoma following lichen planus of the vulva.
AB  - A 58-year-old woman presented with typical cutaneous features of lichen planus
      (LP). She had suffered from vulval pruritus for 3 years, and examination showed
      lesions suggestive of LP on the vulva. Three months later a plaque developed on
      the clitoral hood, and biopsy showed an invasive squamous carcinoma. After
      vulvectomy, features of LP were found in the excised specimen. Vulval LP should
      be carefully monitored for possible malignant transformation.

PMID- 8565260
TI  - Urticaria associated with thyrotoxicosis.
AB  - We report a patient with chronic urticaria which was closely associated with
      elevated levels of thyroxine. The urticaria responded poorly to antihistamines
      and only partially to systemic steroids, but resolved consistently when the
      thyroxine level was reduced to normal. The mechanism for the association may
      involve modulation of the cyclic AMP levels within mast cells.

PMID- 8565261
TI  - Oesophageal webs associated with cicatricial pemphigoid.

PMID- 8565262
TI  - Basal cell carcinoma arising in a naevus sebaceous in a 5-year-old girl.

PMID- 8565263
TI  - Longstanding bilateral cystic chondromalacia of the ear.

PMID- 8565264
TI  - Notalgia paraesthetica and macular amyloidosis.

PMID- 8565265
TI  - St. John Dermatological Society Oration, 1994. Immune responses in leprosy,
      cytokines and new archetypes for dermatology.

PMID- 8565266
TI  - Managing lymphoedema.
AB  - Lymphoedema is perceived by clinicians in the UK as a rare condition for which
      there is no effective treatment. I would like to argue that lymphoedema is in
      fact a common condition which is misunderstood and often poorly managed. To
      explain further the basic physiology of oedema has to be considered.

PMID- 8565267
TI  - Role of IL-4 in delayed type hypersensitivity.
AB  - IL-4 plays a key role in the contact sensitivity skin reaction. This has several
      implications. First, the view that contact sensitivity (CS) is only mediated by
      cells with a Th1 profile of cytokine secretion needs modification, in the light
      of the essential role of IL-4 at the effector stage. Second, the concept of a
      single cell involved in the systemic transfer of CS is no longer tenable, as it
      is known that both alpha beta and gamma delta cells are required. Studies with
      the cell lines (which contain both alpha beta and a few gamma delta cells)
      suggest that this double requirement may involve the action of IL-4 on gamma
      delta cells, which bear receptors for IL-4. Finally, the view that T cell lines
      only transfer CS when injected locally, but not when injected intravenously
      (systemic transfer), is correct but incomplete, as T cell lines actually give
      systemic transfer of CS, providing the cell line or the recipient is treated with
      IL-4.

PMID- 8565268
TI  - Serum levels of soluble CD30 in chronic hepatitis B virus infection.
AB  - There is evidence that both cellular and humoral components of the immune
      response are required for viral clearance to occur in chronic hepatitis B. Recent
      studies demonstrated that CD30 molecule, a member of the tumour necrosis factor
      superfamily of membrane cytokine receptors, is expressed on, and released as a
      soluble molecule (sCD30) by activated T cells producing T helper 2 (Th2)
      cytokines, which modulate antibody responses. To better characterize the
      immunoregulatory mechanisms in chronic hepatitis B virus (HBV) infection, sCD30
      values were evaluated by an ELISA in 90 hepatitis B surface (HBsAg)-positive
      patients with chronic hepatitis, selected on the basis of active viral
      replication and biochemical activity. At presentation abnormal levels (> 20 U/ml)
      of sCD30 were detected in 57 (63%) out of 90 patients with chronic hepatitis B,
      and median value was significantly higher in this group of patients compared with
      that of healthy HBsAg carriers (26.7 versus 10.5 U/ml, P < 0.000 05) and with
      normal controls (26.7 versus 3 U/ml P < 0.000 01). Sequential studies of chronic
      hepatitis B did confirm the association of raised sCD30 levels with the active
      phase of the illness. On the other hand, a significant decrease was noted when
      sCD30 levels at diagnosis and after termination of HBV replication and
      biochemical remission of hepatitis were compared in 10 untreated patients
      (median, 28 U/ml at entry versus 8 U/ml at remission, P < 0.01) and in six
      patients responding to interferon-alpha therapy (median, 29.5 U/ml at entry
      versus 6 U/ml at remission, P < 0.05). The high serum sCD30 levels reported
      during the active phase of HBsAg-positive chronic hepatitis suggest a certain
      degree of immune competence of these patients, at least with respect to a Th2
      type response. These data are in agreement with recent serologic surveys showing
      that most chronic hepatitis B patients do demonstrate ongoing humoral immune
      response to HBV antigens, using novel immunoassays designed to detect antibody in
      the presence of excess serum viral antigen. Th2 functions that mainly promote
      humoral immunity to HBV antigens may be critical, in association with a competent
      virus-specific cytotoxicity, for efficient termination of HBV replication in
      chronic hepatitis B.

PMID- 8565269
TI  - Differential spontaneous expression of mRNA for IL-4, IL-10, IL-13, IL-2 and
      interferon-gamma (IFN-gamma) in peripheral blood mononuclear cells (PBMC) from
      atopic patients.
AB  - Distinct cytokine-producing T cell subsets are well known to play a major role in
      IgE production and to be differentially regulated in allergic patients, although
      the characterization of the type 1/type 2 cytokine pattern in PBMC during
      allergic responses remains to be clearly defined. The aim of this study was to
      determine whether different cytokine profiles are observed directly in PBMC of
      atopic donors. We attempted to study several cytokines (IL-2, IFN-gamma, IL-4, IL
      10 and IL-13) using not only ELISA but also polymerase chain reaction (PCR)
      techniques, because the frequency of cytokine-producing cells in peripheral blood
      is very low. All the patients were selected during their acute symptomatologic
      phase. Data showed a significantly higher production of IL-4 (P = 0.05) and IL-10
      (P < 0.005) as determined by ELISA in phytohaemagglutinin (PHA)/phorbol myristate
      acetate (PMA)-stimulated mononuclear cells of atopic donors compared with
      controls, although spontaneous IL-4 production without stimulation was never
      detected within either atopic or control groups. The reverse-transcriptase (RT)
      PCR technique appeared to be advantageous in that it allowed the detection of the
      spontaneous expression of cytokine mRNA in cells without stimulation. We found a
      clear expression of IL-4 mRNA spontaneously in all atopic patients, whereas
      normal donors in most cases did not show specific signals (P < 0.0001). Less
      differences between atopic subjects and controls were found in IL-10 mRNA
      expression. Although the technique of RT-PCR amplification used in this study is
      semiquantitative, a reproducible and significant (P < 0.001) enhancement of IL-10
      mRNA expression was observed in atopic donors. A heterogeneous expression of IL
      13 mRNA was observed in individuals from the two groups studied, although mean
      levels in atopic donors were slightly enhanced compared with controls (P = 0.02).
      Furthermore, we did not observe any alteration in the expression of the type 1
      derived cytokines such as IFN-gamma and IL-2. In addition, we showed a lack of
      correlation between the expression of serum IgE (total or specific) and
      spontaneous IL-4 mRNA expression. This study showed a tendency of PBMC from
      atopic donors to express a type 2-like cytokine pattern, with IL-4 as the most
      discriminatory cytokine. Additionally, as the level of serum IgE has a low
      predictive value in allergic disease, and as the elevated expression of IL-4 that
      we found was not correlated with serum IgE, we could strongly suggest that the
      measurement of IL-4 in blood mononuclear cells may be of great value in the
      analysis of allergic responses in atopic donors.

PMID- 8565270
TI  - Inverted V delta 1/V delta 2 ratio within the T cell receptor (TCR)-gamma delta T
      cell population in peripheral blood of heart transplant recipients.
AB  - We investigated the levels of TCR-gamma delta T cells and their subpopulations V
      delta 1 and V delta 2 in the peripheral blood lymphocytes (PBL) of 28 heart
      transplant (HTx) patients. Patients (n = 10) receiving cyclosporin A (CsA) for
      treatment of a nephrotic syndrome (NS) and 10 healthy individuals served as
      controls. There was no difference in levels of TCR-gamma delta T cells between
      the different groups. However, an elevated proportion of V delta 1+ gamma delta T
      cells was found in the PBL of HTx patients, especially when these cells were
      present in their graft-infiltrating lymphocyte (GIL) cultures. V delta 1+ gamma
      delta T cells of HTx patients showed normal expression of CD45RO and lacked the
      activation markers CD25 and HLA-DR. After expanding in IL-2-containing medium,
      PBL cultures of HTx patients more often were dominated by V delta 1 cells than
      PBL cultures of controls, in which V delta 2 cells were predominantly grown. The
      aberrant composition of the TCR-gamma delta population in HTx patients was not a
      result of immunosuppressive medication, since the proportion V delta 1+ gamma
      delta T cells was normal in the PBL of the NS patients receiving a similar dose
      of CsA. It is postulated that long-term antigenic stimulation by the graft, at
      low level, might be responsible for the altered composition of the gamma delta
      pool in the HTx patients. Since no donor HLA-specific gamma delta T cells have
      been detected, other ligands, such as heat shock proteins, may be involved.

PMID- 8565271
TI  - Detection of cytokine mRNA-expressing cells in peripheral blood of patients with
      IgA nephropathy using non-radioactive in situ hybridization.
AB  - IgA nephropathy (IgA-N) is considered to be an immune-mediated disorder and
      several immunological abnormalities have been observed. In the present study, we
      optimized non-radioactive in situ hybridization and applied this technique to
      evaluate the degree of expression of various cytokine mRNAs in peripheral blood
      mononuclear cells (PBMC) taken from patients with IgA-N on cytospin preparation.
      Using this method, together with image analysis, we examined the expression of
      mRNA in cells which secrete cytokines, such as IL-2, interferon-gamma (IFN
      gamma), IL-4, IL-5 and IL-6. The expression of these mRNAs was clearly observed
      in monocytes and lymphocytes at a single-cell level. Compared with healthy
      adults, the expression of IL-4 mRNA, IL-5 mRNA and IL-6 mRNA, but not IL-2 mRNA
      or IFN-gamma mRNA, was significantly enhanced. Our results indicate that non
      radioactive in situ hybridization method is a powerful technique for analysis of
      cytokine mRNAs in PBMC at a cellular level. Our results also suggest that mRNA
      expression of IL-4, IL-5 and IL-6, produced by Th2 cells, is increased in
      patients with IgA-N. The abnormal regulatory process involved in cytokine
      expression may play an important immunopathologic role in IgA-N.

PMID- 8565272
TI  - T and B lymphocytes reacting with the extracellular loop of the beta 2-adrenergic
      receptor (beta 2AR) are present in the peripheral blood of patients with
      myasthenia gravis.
AB  - Eighteen percent of patients with myasthenia gravis (MG) have serum antibodies
      against a synthetic peptide corresponding to the second extracellular loop of the
      human beta 2AR (residues 172-197). In this study we examined T and B cell
      responses to the peptide, using assays to detect individual cells secreting
      interferon-gamma (IFN-gamma) and IL-4 or antibodies against the peptide, and by
      measuring thymidine incorporation in response to the peptide. The peptide from
      the beta 2AR induced cytokine secretion from blood mononuclear cells in 67% of MG
      patients, compared with 14-28% of the control groups. Cells secreting antibodies
      binding to the peptide were present in 54% of MG patients and in 19-28% of
      controls. The numbers of beta 2AR-reactive cells were higher in MG patients than
      in controls. Peptide-induced increase in thymidine incorporation in cells was
      also more frequently demonstrated in patients (26%) compared with controls (about
      10%). Activation of cells was dependent on monocytes and on MHC class II DR
      antigen. Based on the pattern of the cytokine secretion induced, beta 2AR
      reactive T cells comprise both T helper type-1 and type-2 subsets. In addition,
      control peptide-reactive T and B cells were much less frequently demonstrated in
      the patients, and the number of such cells did not differ between the groups. Our
      results show that beta 2AR-reactive cells are present in most patients with MG.
      Such autoreactive antibodies and cells might play a role in the pathogenesis of
      the disease by influencing the function of skeletal muscle and immune systems.

PMID- 8565273
TI  - Effect of the expression of DR alpha E beta NOD molecule on the development of
      insulitis and diabetes in the non-obese diabetic (NOD) mouse.
AB  - Previous studies have shown that a transgenic I-E alpha gene, the mouse homologue
      of human DR alpha gene, prevents the development of insulitis and hence of
      diabetes in NOD mice. To investigate the mechanism of this prevention, we
      generated two strains of NOD mice expressing DR alpha E beta molecule: DR alpha
      24-NOD expressing DR alpha E beta molecule on thymic epithelial cells (TEC) and
      bone marrow-derived cells (BDC), and DR alpha-30-NOD expressing DR alpha E beta
      molecule only on the TEC, and these mice were monitored for disease development.
      Because the DR alpha E beta molecule reconstituted I-E controlled immune
      regulation, it would become clear which cell type, TEC or BDC, was responsible
      for the I-E-mediated disease protection. To our surprise, however, DR alpha-24
      NOD developed insulitis and diabetes comparably to non-transgenic littermates.
      This suggested that the difference in structure between DR alpha and E alpha
      molecules contributed to the difference in preventive effect on the development
      of insulitis and diabetes between DR alpha-24-NOD and E alpha-NOD. In an analysis
      of the T cell proliferative responses to glutamic acid decarboxylase (GAD) 65
      derived peptides which were known to be diabetogenic autoantigens, it was shown
      that DR alpha-24-NOD and NOD acquired comparable level of T cell response to GAD
      509-528 but 5-10-fold higher response was observed in E alpha-NOD. This suggested
      that I-ANOD and E alpha E beta NOD molecules could present GAD 509-528 peptide to
      T cells, while DR alpha E beta NOD could not. Furthermore, T cells from DR alpha
      transgenic mice showed proliferative response to antigen-presenting cells from E
      alpha transgenic mice in primary mixed lymphocyte reaction. This also suggested
      that the E alpha E beta molecule does differ in structure and peptide binding
      from the DR alpha E beta molecule. Present data suggested a possibility that the
      T cell repertoire selection, or the T cell response to GAD 65 and/or other
      unknown antigens specifically mediated by I-E molecule, may contribute to the
      prevention of disease development in E alpha-NOD.

PMID- 8565274
TI  - T cell receptor (TCR) V gene segment use in HLA-typed Japanese healthy subjects.
AB  - The expression of 13 different alpha and beta V gene segments of the T cell
      receptor for antigen (TCR) was examined, using V gene-specific MoAbs, on human
      peripheral blood T lymphocytes from 32 healthy Japanese subjects. In addition, to
      examine associations between TCR V gene products and HLA alleles, the HLA class I
      and class II types of all subjects were serologically determined. The
      reactivities of the anti-TCR V-specific MoAbs were, with some significant
      exceptions, similar to those previously described in healthy Caucasian subjects.
      We found a non-random V gene usage as well as a statistically significant bias of
      the expression of eight V beta gene products towards the CD4+ subpopulation, and
      a significant skewness in the usage of V alpha 12 towards the CD8+ population.
      Some subjects showed increased reactivities (above 10%) of certain MoAbs, mainly
      in the CD8+ subpopulation. We found no distinct correlation between any certain
      HLA class I or II allele and TCR V gene usage in the CD8+ or CD4+ subpopulations,
      respectively. In conclusion, the pattern of anti-TCR V-specific MoAb reactivities
      found in CD4+ and CD8+ subsets of peripheral blood lymphocytes of healthy
      Japanese subjects was in general found to match that previously described in
      healthy Caucasian subjects.

PMID- 8565275
TI  - Hepatitis B virus (HBV)-specific in vitro antibody production by peripheral blood
      mononuclear cells (PBMC) after vaccination by recombinant hepatitis B surface
      antigen (rHBsAg).
AB  - To study the immunization induced by rHBsAg, we analysed the in vitro antibody
      production (IVAP) to HBsAg by PBMC from 18 subjects vaccinated by two injections
      on days 0 and 30. HBsAg-specific IVAP was detectable in all subjects after both
      the first and the second injection, and lasted for about 10 days and then
      disappeared. However, when the spontaneous HBsAg-specific IVAP became negative,
      HBsAg stimulation of PBMC cultures induced again a specific HBsAg IVAP. Cultures
      of cell populations separated by erythrocyte rosetting or Percoll density
      centrifugation showed that the cells responsible for spontaneous secretion, after
      in vivo stimulation, were low-density B lymphocytes. High-density B lymphocytes
      were involved in anti-HBs production induced by in vitro stimulation when
      spontaneous secretion disappeared. These data suggest that the IVAP test could be
      a source of important information along with serologic analysis for exploration
      of the immune response to hepatitis B vaccine.

PMID- 8565276
TI  - Adhesion molecule expression and response to chemotactic agents of human monocyte
      derived macrophages.
AB  - Human monocyte-derived macrophages have been proposed as agents of anti-tumour
      immunotherapy. The aim of the present study was to investigate in vitro the
      properties of these cells likely to control their recruitment to the sites of
      inflammation and tumours. The expression of adhesion molecules involved in the
      binding of monocytes to endothelial cells was modified during monocyte-macrophage
      differentiation, with a significant increase in CD11c, CD14 and intercellular
      adhesion molecule-1 (ICAM-1). Monocyte-derived macrophages were sensitive to
      chemoattractants, in particular to the monocyte-specific chemokine monocyte
      chemotactic protein-1 (MCP-1). They responded by an increased expression of
      adhesion molecules and were attracted by the cytokine in an under-agarose
      migration assay. The migration response, however, decreased after days 4-5 of
      monocyte differentiation into macrophage. In conclusion, human monocyte-derived
      macrophages show alterations of surface structures involved in the recognition of
      inflammatory endothelium. This may explain why the cells are poorly recruited to
      the sites of inflammation and tumours when introduced into the circulation.

PMID- 8565277
TI  - Transforming growth factor-beta 1 (TGF-beta 1) down-regulates IgA Fc-receptor
      (CD89) expression on human monocytes.
AB  - IgA is the predominant immunoglobulin in human secretions and the second most
      important immunoglobulin in the circulation on a quantitative basis. The
      clearance of IgA is dependent on the function of at least three types of
      receptors. One of these receptors recognizes the Fc portion of the IgA molecule,
      Fc alpha R, which has been cloned recently. Fc alpha R, also designated CD89, is
      found on a number of cells, including human glomerular mesangial cells, and
      monocytes. In this study we analysed the effect of TGF-beta 1, a cytokine with
      strong immunosuppressive function, on the expression of CD89 on freshly isolated
      monocytes. We found that TGF-beta 1 down-regulates CD89 expression on human
      peripheral blood monocytes in a dose-dependent fashion. Optimal down-regulation
      occurred at a concentration of 5 ng/ml. The down-regulation of CD89 by TGF-beta 1
      is linear in time, with a mean down-regulation of 34 +/- 13% after 24 h. Also at
      the mRNA level, CD89 expression was down-regulated by TGF-beta 1, suggesting
      regulation of CD89 at the transcriptional level. Monocytes pre-treated with TGF
      beta 1 displayed a reduced response to IgA, as measured by IL-6 production by
      monocytes, in contrast to monocytes pre-treated with medium alone. These results
      suggest an important role for TGF-beta 1 in the regulation of CD89. This down
      regulation may have direct consequences for the handling of IgA by human
      monocytes.

PMID- 8565278
TI  - Normal levels of soluble E-selectin, soluble intercellular adhesion molecule-1
      (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) decrease with
      age.
AB  - sE-selectin, sICAM-1, sVCAM-1 and von Willebrand factor (vWF) were assayed in 238
      samples in a longitudinal study of 81 normal children from 9.5 to 15.5 years old.
      Multilevel modelling was used to quantify changes with age. sE-selectin, sICAM-1
      and sVCAM-1 all fell significantly over the age range (by 17%, 16%, and 10%,
      respectively). In contrast, levels of vWF were not age-dependent. Our findings
      highlight the need for age-matched controls when studying cell surface adhesion
      molecules in disease groups, and may imply developmental changes in expression of
      these molecules and their shedding from the cell surface.

PMID- 8565279
TI  - Detection of bilayer phospholipid-binding antibodies using flow cytometry.
AB  - Antiphospholipid antibodies (APL) are usually detected using solid-phase
      immunoassays, where cardiolipin is the most common capture antigen. Phosholipids
      are believed to adopt a monolayer organization when coated onto polystyrene after
      evaporation of the solvent. However, bilayer phospholipids are probably those
      evidenced as microparticles or cell fragments circulating in vivo under various
      pathological circumstances. The surface density of monolayer phospholipids on
      polystyrene is six times lower than that of bilayer phospholipids. In order to
      assess the influence of phospholipid organization on the detection of APL, we
      prepared glass microspheres coated with bilayer phospholipids (cardiolipin,
      phosphatidylcholine, cholesterol). Such lipospheres enabled us to study the
      binding of antibodies in 1:100 diluted plasma samples from patients with
      anticardiolipin antibodies of IgG isotype previously diagnosed by ELISA. Among
      the 39 plasma samples analysed by flow cytometry, 17 showed positive IgG binding
      to lipospheres. Only four additional samples became positive when adding 20
      micrograms/ml apolipoprotein H. The specificity of the binding was demonstrated
      by complete reversibility with 1.4 microM annexin V and with a large excess of
      liposomes of the same composition. The absence of correlation between liposphere
      and ELISA results suggests that different subgroups of antibodies are detected
      depending on the method. The detection of APL using bilayer phospholipids is an
      original assay and may represent a more physiopathological approach to the
      specificity of APL.

PMID- 8565280
TI  - Cross-reactive antibodies between HIV-gp120 and platelet gpIIIa (CD61) in HIV
      related immune thrombocytopenic purpura.
AB  - We have previously demonstrated that immune platelet destruction observed in an
      AIDS-free HIV-infected patient was associated with the presence of a cross
      reactive antibody recognizing both HIV-glycoprotein (gp)120 and platelet gpIIIa
      (CD61). We have now investigated the presence of such antibodies in other HIV
      infected patients, together with the molecular structure of the cross-reactive
      epitope. Platelet gpIIb/IIIa antibodies were characterized in sera from HIV
      infected patients with immune thrombocytopenic purpura by means of an ELISA and a
      radio-immunoprecipitation procedure (RIP). The platelet antibodies were purified
      and tested for their ability to recognize HIV-gp. We also tried to characterize
      the antibody target epitope on HIV-gp120 using recombinant gp and synthetic
      peptides. IgG with anti-gpIIb/IIIa activity were detected, by means of an ELISA
      with purified gpIIb/IIIa, in 101/138 (73%) sera from HIV-infected patients with
      immune thrombocytopenic purpura. The platelet antibodies were purified from 23
      sera by absorption/elution on purified immobilized platelet gpIIb/IIIa, and
      recognition of gpIIIa was confirmed in eight cases with a RIP. Furthermore, the
      presence of a cross-reactive antibody between HIV-gp120 and platelet gpIIIa was
      demonstrated in 18/18 patients (including the eight with a confirmed gpIIIa
      antibody) by the ability of the serum HIV-gp160/120 antibodies to bind to
      purified gpIIb/IIIa. The cross-reactive epitope was shown to be independent of
      the carbohydrate moieties of gp120, since deglycosylation of two recombinant (r)
      gp120s did not abolish antibody binding. However, the antibody did not recognize
      synthetic gp120 peptides spanning 355 of the 516 amino acids of gp120,
      particularly the four regions exhibiting sequences of four or five consecutive
      amino acids that are identical between r-gp120 and gpIIIa. Our results thus
      support the hypothesis that the cross-reactive antibody recognizes the
      conformational structure of gp120. These results strongly suggest that molecular
      mimicry between HIV-gp120 and platelet gpIIIa may be important in the
      pathogenesis of immune thrombocytopenia in AIDS-free HIV-infected patients.

PMID- 8565281
TI  - Mitogenic effect of HIV-infected human T cell lines on mouse B cells mediated by
      surface immunoglobulin.
AB  - Following HIV-1 infection, a number of disorders are induced in both normal T and
      B cells by virus products derived from infected CD4+ T cells. In the present
      study, we found that HIV-infected, but not uninfected, human T cell lines
      generated vigorous blastogenesis and proliferation of freshly isolated mouse B
      cells in a short-term culture. Neither human B cells nor rat B cells showed
      significant responses to the HIV-infected T cell lines in the present condition.
      The mitogenic effect of HIV-infected human T cell line requires direct cell-cell
      interaction between mouse B cells and HIV-infected T cell lines. Since either
      mitomycin c treatment or paraformaldehyde fixation of HIV-infected T cell lines
      resulted in complete loss of the mitogenic effect, it seems that de novo
      synthesized viral products are responsible for this effect. Furthermore, anti
      mouse immunoglobulin antibody inhibited completely the B cell stimulation by the
      HIV-infected human T cell lines. Thus, surface immunoglobulin (sIg) on mouse B
      cells appears to be an essential molecule which transduces activation signals
      from HIV-infected human T cells into cytoplasm of the B cells.

PMID- 8565282
TI  - Generalized immune activation in pulmonary tuberculosis: co-activation with HIV
      infection.
AB  - Parameters of immune activation/differentiation were studied in a group of newly
      diagnosed HIV- and HIV+ pulmonary tuberculosis (TB) patients. Compared with
      controls, HLA-DR expression on both CD4 and CD8 T cells from the HIV- TB patients
      was approximately doubled; HLA-DR on T cells from the HIV+ group was tripled. The
      monocytes from both groups of patients expressed abnormally high levels of the Fc
      gamma receptors I and III. Serum levels of tumour necrosis factor-alpha (TNF
      alpha), neopterin and beta 2-microglobulin were increased in HIV- and even more
      so in HIV+ TB patients. The expression of HLA-DR on T cell subsets and of Fc
      gamma R on monocytes correlated with each other, but not with serum activation
      markers. This pattern of non-specific activation during TB infection may be
      associated with enhanced susceptibility to HIV infection.

PMID- 8565283
TI  - Defective antigen processing associated with familial disseminated
      mycobacteriosis.
AB  - To gain insights into a possible immune defect predisposing to disseminated
      mycobacteria infection, we studied three of six surviving children with
      disseminated Mycobacterium avium complex infection, who had no recognized form of
      immunodeficiency. We used mycobacteria isolated from the patients and diphtheria,
      tetanus and pertussis vaccine (DTP) to study antigen-specific T lymphocyte
      responses. We observed that interferon-gamma (IFN-gamma) production by T cells in
      response to antigens (both mycobacteria and DTP) in these patients with
      disseminated infection was greatly impaired. This defect did not seem to be the
      result of T cell unresponsiveness, as phytohaemagglutinin (PHA) stimulation was
      able to induce high levels of IFN-gamma comparable to those seen in control
      patients with localized infection. Further experiments showed that peripheral
      blood mononuclear cells (PBMC) from patients with disseminated infection were
      able to present influenza haemagglutinin (HA) peptides to specific T cell clones.
      However, this ability was lost when the whole HA protein was used as source of
      antigen. Taken together, these observations support the notion that the primary
      immune defect in these patients with disseminated mycobacterial infection rests
      in the antigen-processing functions of their antigen-presenting cells (APC).
      These findings may provide clues to the wider problem of susceptibility to
      mycobacteria and other intracellular pathogens and have implications in designing
      therapy for these patients.

PMID- 8565285
TI  - Ultraviolet B irradiation and cytomegalovirus infection synergize to induce the
      cell surface expression of 52-kD/Ro antigen.
AB  - Cultured human fibroblasts (MRC-5) have been previously demonstrated to express
      calreticulin, but not Ro autoantigen, on their surface after human
      cytomegalovirus (CMV) infection. The present study addresses the question of
      whether other stimuli, alone or in combination with CMV, can induce the surface
      expression of Ro autoantigens on human fibroblasts. Using a fixed-cell ELISA to
      detect autoantigen expression, a synergistic effect between ultraviolet B (UVB)
      exposure and CMV infection on the surface expression of 52-kD/Ro antigen, but not
      60-kD/Ro or calreticulin, was observed. The enhanced expression of 52-kD/Ro
      antigen was significant and specific, compared with untreated cells, cells
      infected with CMV alone or irradiated with UVB only, and cells subjected to other
      treatments, such as low pH. Immunofluorescence studies confirmed these findings
      and indicated that cells expressed 52-kD/Ro protein on their surface at 24 h
      after a combined UVB and CMV treatment. These studies provide evidence that
      synergy between UVB irradiation and CMV infection may play a role in the
      induction of cell surface expression of the human autoantigen, 52-kD/Ro.

PMID- 8565284
TI  - Cholesterol sulphate-reactive autoantibodies are specifically increased in
      chronic chagasic human patients.
AB  - An antibody reactive with cholesterol sulphate (CS) was characterized in human
      sera by ELISA, erythrocyte and liposome absorption. This antibody was found
      evenly distributed between the IgA and IgM classes, and whilst this was present
      at low titres in the serum of 16% of healthy individuals studied, it was
      significantly elevated in 78% of Trypanosoma cruzi-infected subjects. No
      association was found between antibody levels and the degree of myocardial
      damage. No significant difference in immunoreactivity was found between healthy
      and chagasic subjects using dehydro-epiandrosterone sulphate and pregnenolone
      sulphate and cholesterol, ergosterol, lanosterol, stigmastanol, beta
      stigmasterol, pregnenolone, prednisolone and dehydroepiandrosterone as antigens,
      suggesting that in chagasic sera the whole sterol molecule is important for
      optimal antibody binding. CS-reactive antibodies were easily purified by
      absorption either with CS-bearing liposomes or with dextran sulphate gel and
      further elution with 1.5 M NaCl. The optimal pH of CS-antibody interaction was
      4.0 with 85% binding at pH 7.0. Polylysine strongly decreased the binding of
      these antibodies to the corresponding antigen. Furthermore, these antibodies were
      strongly absorbed by rabbit and guinea pig erythrocyte but not by rat or human
      erythrocyte. In contrast with anti-sulphatide antibodies, no significant increase
      in CS-reactive antibodies was found in dilated cardiomyopathies. Whilst CS itself
      was not detected in T. cruzi lipid extracts, there is an unidentified sulphated
      sterol, which migrates close to standard CS and which strongly binds chagasic but
      not control sera. This latter sterol might be acting in chagasic patients as a
      powerful antigen, triggering specific autoantibody production.

PMID- 8565286
TI  - Prevalence of hepatitis C in patients with primary antibody deficiency.
AB  - Concern over sporadic hepatitis C virus (HCV) infection from treatment with
      contaminated immunoglobulin in patients with immunodeficiency prompted use to
      screen serum from 44 patients for HCV RNA. We found no evidence of either
      horizontal or iatrogenic infection in our Clinic, except in two patients known to
      have received contaminated batches, and in one who had had regular plasma
      infusions. Thus, common variable immunodeficiency (CVID) patients in England do
      not have a high incidence of HCV infection despite exposure to various
      immunoglobulin products. This contrasts with the recently reported high
      prevalence in similar patients in Italy. Although our data reinforce the
      impression that both intramuscular and current licensed i.v. preparations in the
      UK are safe, manufacturers should be encouraged to PCR screen all batches of
      immunoglobulin for HCV.

PMID- 8565287
TI  - Dietary beta-carotene and ultraviolet-induced immunosuppression.
AB  - Ultraviolet (UV)-induced immunosuppression is a critical step in UV
      carcinogenesis, permitting tumour outgrowth. We investigated the effect of
      dietary beta-carotene on UV suppression of contact hypersensitivity (CHS) to
      trinitrochlorobenzene (TNCB) in BALB/c mice. Mice were fed for 10-16 weeks chow
      alone or supplemented with 1% beta-carotene or placebo as beadlets. Serum beta
      carotene was detectable by high performance liquid chromatography (HPLC) analysis
      only in beta-carotene-fed mice (2.06 +/- 0.15 micrograms/ml). Serum retinol was
      0.22-0.27 micrograms/ml in all three groups. Mice (n = 41/dietary group) were
      irradiated with 0, 4.5, 9 or 18 kJ/m2 of UVB and the CHS response was measured.
      Decreased CHS responses were observed in all UV-irradiated groups compared with
      unirradiated controls. UV dose-responses for suppression of CHS derived by first
      order regression analyses of plots of percentage suppression of CHS as a function
      of log10UV dose showed significant slopes (P < 0.02) for all three dietary groups
      and similar residual variances between groups, P > 0.05. The UV dose for 50%
      suppression of CHS was 6.3 kJ/m2 for control, 6.4 kJ/m2 for placebo, and 5.5
      kJ/m2 for beta-carotene-fed mice. No significant differences in slopes or
      elevations between UV dose-responses were observed, P > 0.05. Skin levels of the
      initiator of UV-induced immunosuppression, cis urocanic acid, were determined by
      HPLC in mice given 0 or 9 kJ/m2 of UV (n = 28/dietary group). No significant
      differences were observed between dietary groups (range 35.2-41.1 ng/mg skin, P >
      0.15) We conclude feeding beta-carotene to BALB/c mice does not alter
      susceptibility to UV immune suppression, in contrast to human studies.

PMID- 8565288
TI  - Effects of in vitro hyperthermia on proliferative responses and lymphocyte
      activity.
AB  - Fever is induced by both exogenous products like endotoxin, and endogenous
      cytokines, most notably IL-1 and IL-6, and tumour necrosis factor (TNF). These
      mediators are believed to interact with the hypothalamus, to induce enhanced body
      temperature. However, little is known about the biological effects of fever on
      the function of the immune system. We here report that a 90-min pulse of mild
      hyperthermia (40 degrees C) induces enhanced proliferation of peripheral blood
      mononuclear cells (PBMC). This proliferative response was completely inhibited by
      antibodies to MHC class II, which had no effect on mitogen-induced proliferation
      of PBMC. The enzyme-linked immunospot (ELISPOT) assay is a sensitive method for
      detection of single cells secreting antibodies or cytokines. A 90-min pulse of
      mild hyperthermia (40 degrees C) induced a significantly enhanced immunoglobulin
      production in PBMC, as determined by ELISPOT, indicating B cell activation. The T
      cell cytokine pattern both with and without stimulation with hyperthermia
      differed between individuals. Enhanced interferon-gamma (IFN-gamma) secretion was
      noted at 39-41 degrees C. This IFN-gamma response was inhibited by antibodies to
      MHC class II and thus was MHC class II-restricted and dependent on antigen
      presenting cells. None of the individuals tested showed IL-4 response after
      stimulation with hyperthermia. These findings favour the notion that fever may
      play an important role in immune responses, and it is possible that fever may act
      as a physiological adjuvant, with effects on the immune system both in infection
      and inflammation of other origins.

PMID- 8565289
TI  - Both in vitro and in vivo irradiation are associated with induction of macrophage
      derived fibroblast growth factors.
AB  - Fibrosis in the lung directly underlying the field of irradiation is an almost
      universal long term sequelae of thoracic irradiation. It is assumed to represent
      the consequence of direct damage to local tissues and/or vascular endothelium by
      ionizing radiation. This view, however, is not in keeping with our current
      understanding of fibrotic processes, which suggest that growth factors for
      fibroblasts (including platelet-derived growth factor (PDGF), insulin-like growth
      factor I (IGF-I)) and cytokines stimulating collagen synthesis (notably
      transforming growth factor-beta) are largely responsible for this process. Since
      a major source of these factors is the macrophage, present in large numbers
      within the lung, it appeared possible that radiation-induced fibrosis might be
      mediated by similar mechanisms. Therefore, a study was designed to determine,
      first, whether in vitro irradiation of mononuclear phagocytes could induce the
      release of growth factors for fibroblasts. Second, we wished to ascertain whether
      these same growth factors might also be secreted by bronchoalveolar cells from
      humans who had undergone in vivo thoracic irradiation. The results of this study
      indicate that irradiation of a number of different types of mononuclear
      phagocytes resulted in the dose-dependent synthesis and release of several growth
      factors for fibroblasts, including PDGF, tumour factor-alpha (TNF-alpha) and IGF
      I. Further, cells obtained by bronchoalveolar lavage from patients undergoing
      thoracic radiation spontaneously released PDGF following irradiation. These
      findings strongly support the contention that synthesis and release of macrophage
      derived growth factors for fibroblasts (particularly PDGF and IGF-I) occur after
      thoracic irradiation and play a significant role in the pathogenesis of
      irradiation-induced pulmonary fibrosis in humans.

PMID- 8565290
TI  - Presence of antibodies to replication protein A in some patients with systemic
      lupus erythematosus (SLE).
AB  - Presence of antibodies directed against replication protein A (RPA), a DNA
      binding protein complex composed of three subunits (RPA-70, RPA-32 and RPA-14)
      was investigated among patients with SLE and other autoimmune diseases using
      immunoblot analysis to RPA-70 and RPA-32 recombinant proteins. Anti-RPA
      antibodies were found in two out of 108 sera from SLE patients, one of them
      showing reactivity against RPA-32 and RPA-70 and the other reacting only against
      RPA-32. Sera from 108 patients with other autoimmune disorders as well as from 42
      healthy control individuals were negative. Thus, the frequency of these
      antibodies in SLE is estimated to be 2-3%. The study demonstrates that RPA is one
      target more of the wide array of autoantigens that elicit an immune response in
      SLE. The presence of anti-RPA autoantibodies seems to be circumscribed to a small
      number of patients with SLE.

PMID- 8565291
TI  - A 71-kD heat shock protein (hsp) from Mycobacterium tuberculosis has modulatory
      effects on experimental rat arthritis.
AB  - The effects of a mycobacterial 71-kD hsp antigen have been investigated for its
      ability to modulate arthritis in rats. Subcutaneous injection (base of tail) of
      increasing amounts of hsp71 from Mycobacterium tuberculosis (MTB) produced dose
      dependent differential inhibitory effects on induction of arthritis by MTB and
      CP20961 in rats. As little as 1 microgram of the hsp71 produced a reduction in
      MTB arthritis, whereas complete protection was observed when 50 micrograms were
      administered. When 71-kD-treated rats were challenged with CP20961, all developed
      reduced symptoms of arthritis compared with control rats, but in this model no
      complete protection was observed over the dose range studied. The effects of 71
      kD pretreatment on collagen II arthritis were not significant, but in general
      symptoms of arthritis were milder than in the control group. The same pattern of
      results was observed previously when hsp65 was used in the different models.
      These results show that the modulatory effects of hsp on adjuvant arthritis are
      not restricted to the hsp65 series, but are also mediated by a member of the
      hsp70 family.

PMID- 8565292
TI  - Inhibition of CD95 (Fas/Apo1)-mediated apoptosis by vaccinia virus WR.
AB  - Stimulation of the CD95 (Apo-1/Fas) molecule either by the CD95 ligand or by
      monoclonal antibodies induces programmed cell death by apoptosis in a variety of
      cell lines and primary cells. In this study we observed that infection of B
      lymphoblast and T lymphoblast cell lines with vaccinia virus strain WR and
      recombinant vaccinia WR constructs, but not strain Copenhagen, rendered cells
      refractor to CD95-medicated apoptosis. In particular, vaccinia virus infection
      suppressed anti-CD95 antibody-induced membrane disintegration, apoptotic nuclear
      morphology of cells, and DNA fragmentation. Inhibition of apoptosis was not
      mediated by CD95 down-regulation or reduced binding of anti-CD95 antibody to
      infected cells, and occurred at a time point when cellular metabolism was not yet
      affected by the lytic vaccinia virus infection. Vaccinia virus (WR)-infected
      cells were resistant to CD95 ligand-CD95-mediated lysis by CD4+ and CD8+ T
      lymphocytes. Because cytolysis mediated by CD95 is one of two major mechanisms
      used by cytotoxic T lymphocytes to kill target cells, inhibition of CD95-mediated
      apoptosis may constitute a novel immune escape mechanism for this virus.
      Additionally, this mechanism may contribute to the higher pathogenicity of
      vaccinia virus strain WR compared with strain Copenhagen.

PMID- 8565293
TI  - Expression of mammalian 60-kD heat shock protein in the joints of mice with
      pristane-induced arthritis.
AB  - Previous work has indicated that autoimmunity to the mammalian 60-kD heat shock
      protein (hsp60) may be necessary for the development of pristane-induced
      arthritis (PIA), a murine model of rheumatoid arthritis. To characterize the
      expression of hsp60 in murine joints, immunoblots of joint extracts and frozen
      histological sections prepared from normal or arthritic mice were probed with the
      hsp60-specific MoAb 4B989. Hsp60 could be detected in the joints of mice with PIA
      by both techniques, and was seen to be localized within the inflamed pannus using
      immunhistochemistry. Immunoblotting revealed that lower concentrations of hsp60
      are also present in normal mouse joints, and that the level of expression
      increases with age, in parallel with greater susceptibility to PIA. In other
      studies, it was demonstrated that the titres of serum IgG antibodies reactive
      with the related mycobacterial hsp65, and the in vitro responsiveness of splenic
      T cells to hsp65, are both elevated in older mice. It is considered that the
      results are consistent with the hypothesis that PIA develops following
      environmental priming with mycobacterial hsp65, and the targeting of cross
      reactive T cells to self-hsp60 in the joints.

PMID- 8565294
TI  - Cytotoxic T lymphocytes specific for murine type II collagen do not trigger
      arthritis in B10 mice.
AB  - To investigate the role of cytotoxic T lymphocytes (CTL) in arthritis, we set out
      to induce CTL specific for murine type II collagen (mCII) in a mouse model. The
      primary protein sequence of the murine pro-alpha 1(II) was screened for fragments
      bearing H-2 Db or Kb binding motifs. Six fragments were identified and the
      corresponding peptides synthesized. One of these peptides, peptide P201 (amino
      acid 199-208 in the C-propeptide of the murine pro-alpha 1(II), was found to be a
      strong binder to H-2 Db. When used to treat RMA-S cells at 26 degrees C, peptide
      P201 induced a four-fold increase of surface expression of H-2 Db. Administration
      of the P201-treated RMA-S cells into B10 mice (H-2b) induced strong CTL responses
      against the immunizing collagen peptide. Despite the high frequencies of mCII
      specific CTL precursors in the periphery, however, the immunized mice showed no
      sign of arthritis up to 16 weeks after immunization. Implications of these data
      for autoimmunity and arthritis are discussed.

PMID- 8565295
TI  - Increased mucosal synthesis of rheumatoid factor (RF) in coeliac disease.
AB  - Increased serum levels of RF have been reported in patients with gluten
      sensitivity. The objective of this study was to investigate the in vivo secretion
      of different isotypes of RF in the small bowel in coeliac disease. Nineteen
      patients were investigated by perfusion of a defined jejunal segment, and the
      jejunal perfusion fluid was analysed for the presence of IgA and IgM anti-Fc
      (IgG). Five of the patients studied had serum IgA deficiency. Patients with
      partial/subtotal villous atrophy but no IgA deficiency (n = 7) had a four-fold
      increase of IgM-RF (P < 0.001) and a three-fold increase of IgA-RF (P < 0.001)
      compared with healthy controls (n = 29). Patients with normal jejunal mucosa but
      no IgA deficiency (n = 7) had similar IgA-RF and IgM-RF concentrations to healthy
      controls. Patients with serum IgA deficiency had no IgA-RF detectable in jejunal
      fluid but the highest IgM-RF concentrations, in particular in active disease. The
      coeliac patients had serum levels of IgA-RF and IgM-RF within the reference
      ranges. Jejunal fluid levels of IgA-RF and IgA-anti-gliadin antibodies were
      significantly correlated (P < 0.001). The data indicate that enhanced jejunal
      mucosal production of RF occurs above all in active coeliac disease. The findings
      suggest that the immune response to gluten induces a mucosal RF synthesis.

PMID- 8565296
TI  - Analysis of rearranged T cell receptor (TCR) V beta transcripts in livers of
      primary biliary cirrhosis: preferential V beta usage suggests antigen-driven
      selection.
AB  - The presence of autoantibodies to mitochondrial pyruvate dehydrogenase complex-E2
      (PDC-E2) and self-reactive T cells to PDC suggests that autoimmune mechanisms may
      be involved in the pathogenesis of primary biliary cirrhosis (PBC). Molecular
      analysis of intrahepatic TCR repertoire may provide valuable information on a T
      cell mechanism for PBC immunopathogenesis. We therefore analysed the TCR V beta
      usage in different regions of the livers removed during transplantation from two
      PBC patients. Using reverse transcription and polymerase chain reaction (RT-PCR),
      a limited heterogeneity of rearranged TCR V beta transcripts was demonstrated in
      different locations of the same liver. Sequence analysis of V beta-D beta-J beta
      (CDR3: the third complementarity determining region) showed the presence of
      conserved residues, no random N additions, and a common motif within CDR3. These
      results suggest that T cells homing to PBC liver may be antigen-driven. To
      elucidate further whether an immune deviation related to T helper 1 cell (Th1) or
      Th2 responses may exist in PBC, intrahepatic mRNA expression of IL-2, IL-4 and
      interferon-gamma (IFN-gamma) was examined by the RT-PCR method. IL-2 and IFN
      gamma could be amplified, whereas IL-4 was virtually undetectable in the livers
      from the two patients with PBC. The findings suggest that polarization of
      intrahepatic lymphokine expression toward the Th1-dominant pattern may be
      significant in the immunopathogenesis of PBC.

PMID- 8565297
TI  - Gamma delta T lymphocyte responses to HIV.
AB  - Natural immunity may be involved in controlling viral spread in hosts infected
      with HIV. A panel of gamma delta T cell receptor-positive lymphocyte clones was
      isolated from the peripheral blood of healthy HIV- donors and tested for anti-HIV
      cytotoxic responses. Twelve of 30 (40%) V gamma 9+/V delta 2+ T cell clones, but
      none of seven V delta 1+ T cell clones, displayed lytic activity against HIV
      infected cells. The V gamma 9+/V delta 2+ clones cytotoxic for HIV-infected cells
      also lysed Daudi cells. However, not all V gamma 9+/V delta 2+ clones which lysed
      Daudi targets had the capacity to lyse HIV-infected cells. Some of the gamma
      delta T cell clones were also investigated for potential proliferative responses
      to HIV-infected cells. One V gamma 9+/V delta 2+ T cell clone (ME8-7) and one V
      delta 1+ T cell clone (ME18-2) demonstrated proliferative responses towards HIV
      infected cells. Another V gamma 9+/V delta 2+ clone (VM39) proliferated in
      response to cell-free HIV. Taken together, these results provide direct evidence
      of anti-HIV gamma delta T cell responses in healthy, HIV- persons.

PMID- 8565298
TI  - Differential maturation of avidity of IgG antibodies to gp41, p24 and p17
      following infection with HIV-1.
AB  - We have evaluated solid-phase ELISA IgG antibody avidity studies as a means of
      identifying cases of recent HIV-1 infection. Although separate studies on the
      avidity of anti-gp41 and anti-p24 antibodies in seroconvertors have been
      reported, a comparison of the ability of patients to simultaneously mature their
      immune response to more than one HIV antigen immediately following seroconversion
      appears to be lacking. We have demonstrated a maturation in anti-gp41 avidity
      which reflects the time since seroconversion in all cases. In contrast, however,
      only some patients produced high-avidity anti-p24 or anti-p17 antibodies during
      the same time span. While the avidity of anti-gp41 antibodies remained high in
      cases of non-recent HIV infection, even in the face of advanced disease, we have
      confirmed the findings of others that the avidity of anti-p24 falls before the
      onset of ARC or AIDS. Therefore, whilst the avidity of anti-gp41 antibodies could
      reliably be of value in identifying cases of recent HIV infection, the avidity of
      anti-p24 or anti-p17 antibodies could not, but may be of prognostic value, even
      at an early stage. The time taken to reach maximum anti-p17, anti-p24 and anti
      gp41 titres was variable, but anti-gp41 titres, like anti-gp41 avidity, remained
      high. In contrast, anti-p24 titres fell, even during the early followup period in
      some seroconvertors. Anti-p24 antibody avidity, however, appeared to be a better
      predictor of disease progression in 'remote' cases than anti-p24 titre. The
      avidity and titres of these antibodies are presented in relation to the clinical
      details, p24 antigen status, CD4 and CD8 counts where these are known.

PMID- 8565299
TI  - Establishment of anti-Epstein-Barr virus (EBV) cellular immunity by adoptive
      transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to
      a patient with severe chronic active EBV infection.
AB  - We describe an experience of a specific immune transfer treatment in a patient
      with chronic active EBV infection. The patient had low anti-EBV T cell-mediated
      cytotoxic activity in his peripheral blood mononuclear cells (PBMC), which may
      have been the primary cause of the disease. An EBV-specific cytotoxic T
      lymphocyte (CTL) line was established from PBMC obtained from the patient's
      sister whose human leucocyte antigens (HLA) are identical to patient's. The
      patient received three courses of intravenously administered CTL at 3-week
      intervals. The number of the cells was increased with each course of treatment.
      After infusion of the T cell line, anti-EBV CTL activity was detected in the
      patient's PBMC. CTL activity increased markedly after the second course of immune
      transfer therapy. The amount of EBV DNA in the patient's plasma showed transient
      but repeated decreases. Serum levels of tumour necrosis factor-alpha (TNF-alpha),
      which had elevated before treatment, began to decrease after initiation of
      treatment. No adverse effects were directly associated with CTL infusions.
      Despite having previously received a pneumococcal vaccine and prophylactic
      antibiotics, the patient died of infection caused by Streptococcus pneumoniae
      bacteraemia 27 days after the third infusion. Although the long-term efficacy and
      safety of this therapy remains to be established, our findings suggest that
      adoptive transfer of CTL specific for EBV obtained from an HLA-matched donor
      might be a promising treatment for patients with chronic active EBV infection.

PMID- 8565300
TI  - Virus-specific cytotoxic T cell responses are associated with immunity of the
      cottontop tamarin to Epstein-Barr virus (EBV).
AB  - The cytotoxic responses of peripheral blood lymphocytes from cottontop tamarins
      to in vitro restimulation with autologous lymphoblastoid cell lines (LCL) were
      assayed. Lymphocytes from immune tamarins that had recovered from EBV challenge
      developed potent cytotoxicity for natural killer (NK) cell targets and for
      autologous LCL. The cytotoxicity for LCL targets was EBV-specific, as B cell
      blasts uninfected with EBV were not killed. The cell lines could be maintained by
      repeated stimulation with LCL and the addition of IL-2. Flow cytometry showed
      that they were T cell lines expressing CD2, CD3, CD4, CD8 and CD25. Dual-colour
      flow cytometry revealed two subpopulations, one CD4+ CD8+ population and the
      other CD4- CD8+. After separation by magnetic cell sorting both subpopulations
      were shown to be cytotoxic and the CD4+ CD8+ fraction was also shown to be MHC
      class II-restricted; the MHC restriction of the CD8+ subpopulation could not be
      determined. The unseparated T cells and both the subpopulations were able to
      inhibit LCL outgrowth in vitro. In contrast, PBL from naive tamarins stimulated
      by autologous LCL developed less NK cell cytotoxicity and little cytotoxicity for
      LCL. The cytotoxic response was enhanced at higher levels of LCL stimulation, but
      the cells were unable to inhibit LCL outgrowth in vitro. We conclude that
      cytotoxic responses capable of inhibiting LCL growth in vitro correlate with in
      vivo immunity in the tamarin model and provide a basis for understanding the
      mechanism of vaccine-induced immune protection.

PMID- 8565301
TI  - Subclasses of IgA antibodies in serum and saliva samples of newborns and infants
      immunized against rotavirus.
AB  - Little is known about subclass levels of IgA in serum or saliva of infants in the
      perinatal period. We have previously shown that very young infants are capable of
      responding to an experimental rotavirus vaccine with both serum and salivary IgA,
      and that small amounts of IgA are already detectable in cord blood of these
      infants. In the present study, total IgA1 and IgA2 antibodies in serum and saliva
      samples of some of these infants at birth, at 6 weeks of age, and at 12 weeks of
      age, were determined by a quantitative ELISA. Also, subclass-specific IgA
      antibodies to the rotavirus group A common antigen were determined by ELISA. The
      ratio of average serum concentrations of IgA1 to IgA2 for 14 infants at 6 weeks
      of age was 19:1, while in saliva it was 5:1. Between 6 and 12 weeks of age levels
      of serum IgA1 increased by 25%, while levels of IgA2 did not increase
      perceptibly. Concentrations of IgA1 were higher in infant sera than in saliva,
      while concentrations of IgA2 were slightly higher in saliva than in serum. When
      calculated as specific ELISA units per mg IgA1, more salivary IgA1 was specific
      for rotavirus than serum IgA1. Further studies are needed to determine when
      infant IgA2 levels rise to values more characteristic of children and adults.
      This may be of significance for infant mucosal immunizations if secretory IgA2,
      more resistant to bacterial proteases than IgA1, is required for efficient
      defence of the respiratory and intestinal tracts.

PMID- 8565302
TI  - Interferon-gamma (IFN-gamma) treatment decreases the inflammatory response in
      chronic Pseudomonas aeruginosa pneumonia in rats.
AB  - In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic
      fibrosis (CF), we studied whether the inflammatory response could be altered by
      intraperitoneal treatment with recombinant rat interferon-gamma (rrIFN-gamma).
      Rats were treated either before or after intratracheal challenge with P.
      aeruginosa embedded in alginate beads. Rats treated after challenge had a
      significant reduction in the severity of macroscopic lung inflammation compared
      with rats treated before challenge (P = 0.004) and controls (P = 0.003). The
      histopathology in controls was dominated by numerous polymorphonuclear leucocytes
      (PMN) (> or = 90%) surrounding the alginate beads like in CF. This could be
      caused by a Th2-like response. In contrast, a complete shift to a chronic-type
      inflammation dominated by mononuclear leucocytes (> or = 90% lymphocytes and
      plasma cells) and granulomas was observed in both rrIFN-gamma-treated groups of
      rats. This could be caused by a Th1-like response. There was no significant
      difference in lethality between the groups, and the antibody titres against P.
      aeruginosa sonicate and alginate were similar in the treated rats and controls.
      Since the ongoing lung tissue damage in CF patients has been shown to be caused
      by elastase secreted by PMN, which dominate the P. aeruginosa lung infection, our
      findings offer a possible new strategy of modifying the inflammatory response in
      CF patients.

PMID- 8565303
TI  - Phospholipids and reactive nitrogen intermediates collaborate in expression of
      the T cell mitogenesis-inhibitory activity of immunosuppressive macrophages
      induced in mycobacterial infection.
AB  - We studied the role of phospholipids and nitric oxide in expression of the
      suppressor activity of splenic macrophages induced by Mycobacterium avium
      intracellulare complex infection (MAIC-induced macrophages) in mice against
      mitogenic response of concanavalin A (Con A)-stimulated splenocytes (SPC) as
      follows. First, phosphatidylserine (PS) and phosphatidylinositol were found to
      suppress Con A-induced mitogenesis of SPC via inhibition of IL-2 production and
      acquisition of IL-2 reactivity in Con A-stimulated T cells. The mitogenesis
      inhibitory activity of PS was increased when SPC were cultured under mildly
      acidic condition (pH 6.3). When SPC were pretreated with PS for 24 h prior to Con
      A blastogenesis, their mitogenic response was irreversibly abrogated. Second, NG
      monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthase, was found to
      attenuate in part the expression of the suppressor activity of MAIC-induced
      macrophages. Third, reactive nitrogen intermediates (RNI) including NO generated
      from acidified NO2- exerted potent inhibitory activity against SPC mitogenic
      response, and the suppressive activity of RNI was significantly augmented by the
      combination with PS. These findings indicate that phospholipids and RNI plays an
      important role in the expression of suppressor activity of MAIC-induced
      macrophages as the effector molecules.

PMID- 8565304
TI  - Expression of Mycobacterium tuberculosis MPT64 in recombinant Myco. smegmatis:
      purification, immunogenicity and application to skin tests for tuberculosis.
AB  - Proteins secreted across the cell wall of mycobacteria are important antigens
      recognized early in the host response to mycobacterial infection. MPT64 is a 23
      kD secreted protein restricted to members of the Mycobacterium tuberculosis
      complex which elicits T cell responses and cutaneous DTH reactions in Myco.
      tuberculosis-infected animals. Patients with tuberculosis and their tuberculin
      positive contacts respond to the protein, but recipients of bacille Calmette
      Guerin (BCG) vaccine strains lacking the mpt64 gene do not. In the present study,
      we describe the development of a unique recombinant mycobacterial vector which
      secretes the encoded Myco. tuberculosis protein MPT64 at high levels into the
      culture filtrate, from which the protein is isolated by a single-step affinity
      chromatographic step. The purified protein was recognized by both polyclonal and
      monoclonal anti-MPT64 antibodies. The T cell reactivity of the protein was
      confirmed by its ability to stimulate human anti-rMPB64 T cell lines. The Myco.
      smegmatis recombinant MPT64 protein was superior to the Escherichia coli rMPB64
      protein, which has identical amino acid sequence, in eliciting cutaneous DTH
      reactions in guinea pigs sensitized with Myco. tuberculosis. Animals sensitized
      with BCG strains lacking the mpb64 gene failed to respond to MPT64. Similarly,
      interferon-gamma (IFN-gamma) responses in tuberculosis patients and their
      contacts were higher to the Myco. smegmatis form of the protein. The potential of
      this form of the Myco. tuberculosis MPT64 protein as a skin test reagent for
      tuberculosis is discussed.

PMID- 8565305
TI  - Administration of anti-CD3 monoclonal antibody during experimental Chagas'
      disease induces CD8+ cell-dependent lethal shock.
AB  - The injection of the 145-2C11 anti-CD3 MoAb in mice induces a polyclonal T cell
      activation resulting in the release of several cytokines, including interferon
      gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). As these
      cytokines are known to be involved in the host defence against Trypanosoma cruzi,
      we measured serum levels of IFN-gamma and TNF-alpha after injection of the 145
      2C11 MoAb in the course of experimental murine Chagas' disease. Compared with
      control mice, T. cruzi-infected BALB/c mice were found to be primed to secrete
      very high levels of IFN-gamma and TNF-alpha from the second and the first week of
      infection, respectively, up to the chronic phase. In vivo cell depletion
      experiments indicated that CD8+ T cells were responsible for these dramatic
      hyperproductions of IFN-gamma and TNF-alpha. While all control mice survived anti
      CD3 MoAb injection, a high lethality rate was observed in T. cruzi-infected mice
      within 24 h after anti-CD3 MoAb challenge. Pretreatment with neutralizing anti
      IFN-gamma MoAb or depletion of CD8+ T cell population dramatically decreased the
      mortality induced by anti-CD3 MoAb in T. cruzi-infected mice. Finally, we showed
      that anti-CD3 MoAb injection in T. cruzi-infected mice was followed by a massive
      release of nitric oxide (NO) metabolites, which was partially reduced by IFN
      gamma or TNF-alpha neutralization. The administration of the NO synthase
      inhibitor N-nitro-L-arginine methyl ester (L-NAME) before anti-CD3 MoAb challenge
      did not prevent and even enhanced lethality in T. cruzi-infected mice, suggesting
      that NO overproduction and lethal shock are not causally related. We conclude
      that injection of anti-CD3 MoAb in the course of experimental Chagas' disease
      induces a CD8+ cell-dependent shock mediated by IFN-gamma and TNF-alpha.

PMID- 8565306
TI  - Immune dysregulation in Ethiopian immigrants in Israel: relevance to helminth
      infections?
AB  - The infectious disease background and particularly the helminth infections that
      are endemic in Africa could have profound effects on the host immune system.
      Studies that we have performed on an Ethiopian HIV- immigrant population that has
      recently reached Israel, lend support to this notion. They have indeed revealed a
      very high prevalence of helminth and several other infections with an extreme
      immune dysregulation, consisting of: (i) highly elevated plasma IgE, IgG,
      placental isoferritin, p75 soluble TNF receptor (sTNFR) levels and very high
      blood eosinophilia; (ii) increased secretion from phytohaemagglutinin (PHA)
      simulated peripheral blood mononuclear cells (PBMC) of the cytokines IL-2, IL-4,
      IL-10 and p75 sTNFR, and decreased secretion of interferon-gamma (IFN-gamma) and
      IL-6; (iii) increased and decreased surface expression of p75 TNFR and IL-6
      receptor on lymphocytes, respectively. The causal relationship between this
      immune dysregulation and the infectious background is highly suggestive, and
      could have far-reaching implications in the resistance to other infections.

PMID- 8565307
TI  - Ivermectin-induced immunopotentiation in onchocerciasis: recognition of selected
      antigens following a single dose of ivermectin.
AB  - Onchocerciasis is associated with blindness and gross skin changes, believed to
      be a consequence of the immune response to antigens released from the offspring
      of the female worm of Onchocerca volvulus, the microfilariae (mf). An effective
      microfilaricidal drug is now available which quickly reduces the mf burden
      without affecting the adult worm. There exist foci in onchocerciasis endemic
      areas where some of the patients have many mf in their skin but relatively few
      clinical symptoms. This state of hyposensitivity is believed to be due to
      immunosuppression. The aim of this study was to address the question of the basis
      of, and the effect of ivermectin treatment on this immunosuppression. Female
      adult worms of O. volvulus were used as whole or fractionated antigens to
      stimulate peripheral blood mononuclear cells. Microfilariae are found in the
      reproduction tract of the female worms, and thus an antigen preparation of the
      female adult O. volvulus contains both exclusive adult antigens as well as
      antigens from microfilariae. Cells were obtained from onchocerciasis patients,
      individuals of similar socio-economic status living in the same Ghanaian village,
      but who showed no parasitological or clinical evidence of onchocerciasis (exposed
      endemic controls), healthy Ghanaians living in areas where transmission of
      onchocerciasis does not seem to occur (non-exposed endemic controls) and
      unexposed healthy Swedish donors. As a group, cells from onchocerciasis patients
      proliferated to a lesser degree than cells from the exposed endemic control and
      the non-exposed endemic control groups to the whole worm antigen, whereas the
      phytohaemagglutinin (PHA) response was strongest in the patients. Proliferative
      responses of above 1000 ct/min to fractions of the worm extract were only evident
      in the cells from a few individuals in each of the various groups. However, 28
      days following ivermectin treatment, cells from all onchocerciasis patients were
      able to mount significantly enhanced proliferation to a fraction of approximately
      96 kD (fraction 3), while only four of nine of this group showed an increased
      response to the whole worm antigen. The proportional increase in the response to
      the whole organism in these individuals was of a much lower magnitude than the
      increased response to fraction 3. The O. volvulus antigen-specific
      immunosuppression observed in these onchocerciasis patients appears to be due to
      suppressive antigens which have the capacity to mask the potential response to
      selected antigens of O. volvulus, and ivermectin treatment possibly modulates the
      immune response, allowing for stepwise recognition of such antigens. Since
      ivermectin treatment kills only the microfilariae and not the adult worm, the
      putative suppressive antigens would be expected to be from the microfilariae.

PMID- 8565308
TI  - T cell responses to myeloperoxidase (MPO) and proteinase 3 (PR3) in patients with
      systemic vasculitis.
AB  - T cell-mediated immune responses are likely to be important in the pathogenesis
      of systemic vasculitis. However, identifying the T cells involved has proved
      difficult, and there are conflicting reports regarding T cell proliferation in
      response to different autoantigens. Perinuclear (P) and cytoplasmic (C) anti
      neutrophil cytoplasmic antibodies (ANCA) are closely associated with systemic
      vasculitis, and are generally specific for MPO or PR3, respectively. We studied
      the proliferative responses to MPO and PR3 of peripheral blood mononuclear cells
      from patients with P-ANCA or C-ANCA specific for these antigens by ELISA. These
      responses were compared with those of normal controls, and of disease controls
      with P- or C-ANCA not specific for MPO or PR3. The patient group as a whole
      showed significant T cell proliferation in response to the autoantigens compared
      with controls (P = 0.005). Cells from nine of 13 P-ANCA-positive, anti-MPO
      positive patients proliferated in response to MPO, compared with five of 16
      controls (P = 0.04). Cells from five of eight C-ANCA-positive, anti-PR3-positive
      patients proliferated in response to PR3, compared with two of 11 controls (P =
      0.05). These experiments demonstrate that patients with P-ANCA or C-ANCA possess
      T cells which respond to MPO or PR3, respectively. As in other autoimmune
      diseases, responses to both antigens were also seen in a proportion of healthy
      controls. Further analysis of these responses will be important in understanding
      the pathogenesis of systemic vasculitis and in designing specific immunotherapy.

PMID- 8565309
TI  - Antibodies to proteinase 3 mediate expression of vascular cell adhesion molecule
      1 (VCAM-1).
AB  - VCAM-1 was first identified as an adhesion molecule induced on human endothelial
      cells (HEC) by inflammatory cytokines such as IL-1, tumour necrosis factor (TNF),
      and lipopolysaccharide (LPS). The molecule binds to a variety of leucocytes,
      including B cells, T cells, basophils, eosinophils and monocytes. Vascular
      expression of VCAM-1 has been associated with a number of disease states,
      including rheumatoid arthritis and vasculitis. The detection of anti-neutrophil
      cytoplasmic antibodies (ANCA), especially to proteinase 3 (PR3), has become
      important in the diagnosis of Wegener's granulomatosis (WG) and related
      vasculitides. Recently we were able to demonstrate a direct effect of anti-PR3
      antibodies on neutrophil-endothelial interactions (Blood 1993; 82:1221). Binding
      of anti-PR3 antibodies to their antigen translocated into the membrane of HEC
      leads to an enhanced adhesion of neutrophils via induction of E-selectin (Clin
      Exp Immunol 1993; 94:440). The aim of this study was to investigate the effect of
      anti-PR3 antibodies on the expression of VCAM-1. HEC were isolated from umbilical
      vein and cultured on microtitre plates. After preincubation with purified anti
      PR3 antibody, purified control antibodies (SS-A, SS-B, RNP) (IgG and F(ab')2
      fragments) or different cytokines (controls), VCAM-1 was detected on the surface
      of unfixed HEC by cyto-ELISA and polymerase chain reaction analysis. Incubation
      of HEC with anti-PR3 antibodies led to a marked increase of endothelial VCAM-1
      expression with a peak after 8 h. Incubation with TNF-alpha also led to maximal
      VCAM-1 expression after 4-6 h (control). Increased adhesion of T lymphocytes to
      HEC after binding of anti-PR3 antibodies to their antigen could be confirmed by
      performing adherence assays. This effect could be inhibited by antibodies to VLA
      4. In conclusion, we have been able to show that cytokine-like effects of anti
      PR3 antibodies on HEC are not limited to induction of neutrophil adhesion. Anti
      PR3 antibodies may thus contribute to the regulation of T lymphocyte migration
      from the blood by HEC in ANCA-related vasculitides.

PMID- 8565310
TI  - T cell clones from a Sjogren's syndrome salivary gland biopsy produce high levels
      of IL-10.
AB  - Sjogren's syndrome (SS) is characterized by a focal periductal salivary gland
      infiltrate consisting mainly of T and B lymphocytes. Most of the T cells bear the
      memory CD4+ Th1-like phenotype and express high levels of class II, though CD8+
      cells are also present. We have studied 17 labial salivary gland and 15
      peripheral blood T cell clones from a patient with primary SS. The tissue clones
      were 71% CD8+ and 29% CD4+, and the peripheral blood-derived clones were 60% CD8+
      and 40% CD4+. The CD4+ T cell clones from both the salivary gland and autologous
      peripheral blood were of the Th1 phenotype, in that they produced interferon
      gamma (IFN-gamma) and IL-2 but very little IL-4 after 24 h stimulation with
      phorbol myristate acetate and anti-CD3 antibody. The salivary gland-derived CD4+
      clones produced 15 times more IL-10 (7.92 ng/ml) than peripheral blood-derived
      CD4+ clones (0.52 ng/ml, P < or = 0.02). The tissue CD8+ clones produced 1.2
      times (P < 0.04) more IFN-gamma and CD4+ clones produced 3.5 times less IL-2 (P <
      0.02) than the respective PBM-derived clones. The accumulation of Th1-type cells
      producing high levels of IL-10 in the salivary gland suggests a specific
      immunoregulatory function at the site of inflammation in SS.

PMID- 8565311
TI  - Treatment with an anti-CD4 monoclonal antibody strongly ameliorates established
      rat adjuvant arthritis.
AB  - Some experimental arthritic diseases can be prevented by treatment with anti-CD4
      MoAbs. Trials with ongoing disease have not been successful so far. The aim of
      this study was to ascertain whether W3/25 could reverse adjuvant arthritis (AA),
      when beginning treatment on day 14, i.e. when the disease was established.
      Moreover, one group of animals treated with the anti-CD4 MoAb received OX8 MoAb
      at the same time, thus depleting CD8+ cells from circulation. During treatment
      with W3/25, a strong amelioration of inflammatory signals were observed, as
      assessed by means of paw volume increase and arthritic score. However, when
      treatment stopped, a rebound to arthritis signals occurred. The parallel
      depletion of CD8+ cells did not modify these effects, thus the combined treatment
      W3/25 + OX8 gave the same amelioration as treatment with W3/25 alone. These
      findings indicate that CD4+ cells play an important role in perpetuating rat AA.
      Moreover, CD8+ cells do not seem to have a regulatory role int he CD4+ cells
      responsible for the inflammatory response.

PMID- 8565313
TI  - Presence of covalent bonds between immune deposits and other macromolecules in
      murine renal glomeruli.
AB  - Microscopic studies have suggested that immune deposits persist for a long time
      in subepithelial areas of renal glomeruli in human diseases and in experimental
      models. This study showed quantitatively that in an experimental murine model
      radiolabelled antibodies in subepithelial immune deposits remained constant for 9
      months at about 3 micrograms/mouse. The extraction of these antibodies was
      incomplete with 1% SDS at 8 months after immune deposit formation. Furthermore,
      in the extracted material some antibodies were covalently bound to other
      molecules. This study demonstrates that covalent bond formation contributes to
      the persistence of immune deposits in renal glomeruli.

PMID- 8565312
TI  - IL-6 mRNA synthesis by peripheral blood mononuclear cells (PBMC) in patients with
      chronic renal failure.
AB  - We measured levels of IL-6 mRNA in PBMC obtained from patients with chronic renal
      failure, using polymerase chain reaction (PCR). PBMC were isolated from 45
      patients on haemodialysis (HD) at the start of HD. PBMC were also isolated from
      35 patients on HD at the end of HD, 23 patients on continuous ambulatory
      peritoneal dialysis (CAPD), 24 undialysed patients with chronic renal failure
      (CRF), and 19 healthy controls. Total RNA was extracted from PBMC with RNA zol
      and reverse transcribed into cDNA. To prepare samples containing identical
      amounts of beta-actin cDNA, we performed competitive PCR by co-amplifying serial
      dilutions of mutant templates containing a single point mutation which generated
      a unique Eco RI site. Next, to measure IL-6 cDNA semiquantitatively in the
      samples containing identical amounts of beta-actin (100 pg), we performed PCR
      amplification using 2 fg of the IL-6 mutant template containing a unique Eco RI
      site. Higher levels of IL-6 mRNA in the PBMC were observed in the HD patients
      than in the CAPD patients and healthy controls. The levels of IL-6 mRNA in the
      PBMC at the end of HD were not significantly higher than those at the start of
      HD. These results suggest that the dialysis session itself did not significantly
      affect IL-6 mRNA levels in the PBMC, but that chronic stimulation by maintenance
      HD may be associated with higher levels of IL-6 mRNA observed in HD patients.

PMID- 8565314
TI  - Regulation and production of IL-8 by human proximal tubular epithelial cells in
      vitro.
AB  - A number of inflammatory kidney diseases are associated with interstitial
      nephritis and influx of leucocytes in the renal interstitium. Potentially the
      influx of neutrophils in the interstitium may be induced by the chemotactic
      cytokine IL-8. In the present study we have analysed the production of IL-8 by
      cultured human proximal tubular epithelial cells (PTEC) in response to a number
      of proinflammatory cytokines. Primary cell lines of proximal tubular epithelium
      obtained from ten different kidneys, and cultured under serum-free conditions,
      were found to produce IL-8 to different degrees from not detectable levels up to
      10.8 +/- 1.5 ng IL-8 per 1 x 10(5) cells in 72 h. Gel filtration chromatography
      of PTEC supernatant indicated that the size of IL-8 of PTEC is 15.1 and 8.1 kD,
      and is chemotactically active for polymorphonuclear neutrophils (PMN). Addition
      of 0.5 ng/ml rIL-1 alpha or 1000 U/ml recombinant tumour necrosis factor-alpha
      (rTNF-alpha) to the culture media of PTEC induced an up-regulation of IL-8
      production up to 6.3-fold and 3.0-fold, respectively. The up-regulation by IL-1
      alpha and TNF-alpha was dose- and time-dependent. In contrast, 500 U/ml
      recombinant interferon-gamma (rIFN-gamma) down-regulated the production of IL-8
      3.4-fold. Northern blot analysis showed that IL-1 alpha and TNF-alpha increased
      the expression of IL-8 mRNA, whereas IFN-gamma reduced IL-8 mRNA expression.
      Taken together, these experiments indicate that human PTEC are a potential source
      of IL-8 in the kidney, and that IL-8 produced in the proximal tubule can be
      induced by various proinflammatory cytokines.

PMID- 8565315
TI  - Gluten activation of peripheral blood T cells induces a Th0-like cytokine pattern
      in both coeliac patients and controls.
AB  - Coeliac disease is apparently a T cell-mediated disease, precipitated in the
      proximal small intestine of susceptible individuals by gluten. Preferential
      presentation of gluten peptides most probably takes place in coeliac mucosa by
      the disease-associated HLA-DQ2 and -DQ8 molecules. In peripheral blood, however,
      both HLA-DR, -DQ and -DP-restricted T cell responses to gluten have been
      observed. We examined gluten-specific T cell clones (TCC) derived from peripheral
      blood for cytokine production to see if their profiles were related to the HLA
      restriction or the disease state of the donors. As previously found for mucosal
      TCC, the main product was interferon-gamma (IFN-gamma), often with additional IL
      4, IL-5, IL-6, IL-10, tumour necrosis factor, and transforming growth factor
      beta. Regardless of restriction element or disease state, gluten-reactive TCC
      from peripheral blood therefore seem to secrete cytokines compatible with a Th0
      profile.

PMID- 8565316
TI  - Loss of the CD5+ and CD45RAhi B cell subsets in alcoholics.
AB  - Chronic alcoholics are frequently immunodeficient, have polyclonal
      hypergammaglobulinaemia, and often have autoantibodies. Recent work in other
      diseases has shown that functional distinctions of possible relevance to
      autoimmunity and immunodeficiency can be found among the B cell subsets defined
      by differential expression of the surface markers CD5 and CD45RA. Therefore, we
      have evaluated the CD5, CD45RA B cell subsets of both chronic alcoholics without
      evidence of active liver disease (AWLD), and alcoholics admitted for acute
      alcoholic liver disease (ALD). Mean B cell numbers were normal in AWLD, but
      significantly reduced in ALD. Analysis of B cells by three-colour flow cytometry
      in 20 patients and 29 controls revealed a sharp decrease in the percentage of
      alcoholics' B cells which were CD5+, 37.6% versus 16.3%, P < 0.000 01; absolute
      CD5+ B cell numbers were similarly reduced (58.9 cells/microliters versus 20.9; P
      = 0.0012). In addition to the loss of CD5+ B cells, there was a reduction in the
      percentage of B cells which are CD5- CD45RAhi, leaving many patients with a B
      cell profile which was predominantly CD19+ CD5- CD45RAlo. This subset appears
      phenotypically similar to the IgM-producing CD5- CD45RAlo subset described by
      others, and may be enriched for autoantibody-producing cells. One outlier patient
      was an ALD with 61% of B cells which were CD5+, which also is a profile
      consistent with increased autoantibody production.

PMID- 8565317
TI  - Glucocorticoids induced down-regulation of glucocorticoid receptor mRNA
      expression in asthma.
AB  - Although their precise mechanism of action remains to be elucidated,
      glucocorticoids represent the most effective therapy in the treatment of asthma.
      Interactions between the glucocorticoid receptor and the AP-1 complex have been
      shown to regulate the transcription of some genes, including glucocorticoid
      receptor itself. The aim of the present study was to compare the expression of
      mRNA for glucocorticoid receptor in human blood monocytes obtained from seven
      unstable untreated asthmatic patients who were subsequently treated with high
      doses of parenteral corticosteroid (methyl prednisolone 120 mg/day) for 10 days.
      mRNA expression was identified after RNA extraction using RNAzol and analysed
      after reverse transcriptase, by polymerase chain reaction using a
      semiquantitative competitive hybridization assay. All asthmatic patients showed
      an improvement in their FEV1 values after corticosteroid treatment (per cent of
      predicted value 68.28 +/- 4.93 versus 95.57 +/- 6.41, P < 0.02), and a
      significant decrease for glucocorticoid receptor mRNA expression (P < 0.02) was
      observed in their monocytes. This is the first report of an ex vivo down
      regulation for the glucocorticoid receptor mRNA expression, following
      corticosteroid treatment.

PMID- 8565318
TI  - Tissue-dependent differences in the asynchronous appearance of mast cells in
      normal mice and in congenic mast cell-deficient mice after infusion of normal
      bone marrow cells.
AB  - The time courses of the appearance of tissue mast cells in six sites were
      compared in normal WBB6F1(-)+/+ mice (+/+) and in congenic mast cell-deficient
      WBB6F1-W/Wv mice (W/Wv) that received an intravenous infusion of bone marrow
      cells from +/+ mice (BM-->W/Wv). As assessed by morphometric analysis of Carnoy's
      solution-fixed, methylene blue-stained tissue sections, the density of mast cells
      in the stomach mucosa, stomach submucosa, and spleen of +/+ mice reached maximal
      levels by 8 weeks of age, whereas the density of mast cells in the skin,
      extraparenchymal airway walls, and lung parenchyma did not reach maximal levels
      until 18 weeks of age. When 8-week-old W/Wv mice were infused with 2 x 10(7) bone
      marrow cells from /+/ mice, mast cells appeared in the stomach mucosa and
      submucosa after 2.5 weeks, in the spleen and extraparenchymal airway walls after
      5 weeks, and in the lung parenchyma after 10 weeks. Twenty weeks after bone
      marrow infusion, the mast cell densities in the spleen, stomach mucosa, and
      stomach submucosa were seven-, 13-, and five-fold greater, respectively, than
      those in age-matched +/+ mice, but were eight-, two-, and five-fold lower in the
      skin, extraparenchymal airway walls, and lung parenchyma, respectively. Thus,
      those tissues that in +/+ mice reached maximal mast cell densities earlier
      exhibited abnormally high mast cell densities in BM-->W/Wv mice, and those that
      reached maximal mast cell densities later in +/+ mice had abnormally low mast
      cell densities in BM-->W/Wv mice. Immunological and inflammatory responses are
      often compared in W/Wv and BM-->W/Wv mice to assess mast cell dependency. Our
      results indicate that the capacity to restore a mast cell-dependent response in a
      particular tissue of the latter mice may relate to the local mast cell density
      and whether the immunological challenge activates mast cells only in that tissue
      or systemically with attendant widespread release of proinflammatory mediators.

PMID- 8565319
TI  - Effect of rapamycin on the expression of the IL-2 receptor (CD25).
AB  - The immunosuppressive macrolide rapamycin inhibits cytokine-driven proliferation
      of lymphocytes, acting at a later stage of T lymphocyte activation than the
      related compound FK506 or cyclosporin, which block IL-2 transcription. However,
      the effect of rapamycin on the expression of the IL-2 receptor alpha-chain (CD25)
      is less well documented. This study has investigated the effect of rapamycin on
      mRNA levels of CD25 and membrane expression of IL-2 receptor in human primary T
      lymphocytes activated by various stimuli. Rapamycin surprisingly inhibits CD25
      upregulation subsequent to anti-CD3 or ionomycin stimulation. These effects are
      not secondary to an IL-2-mediated CD25 up-regulation, as rapamycin inhibits
      neither IL-2 synthesis nor IL-2-induced CD25 mRNA. Interestingly, sensitivity to
      rapamycin correlates with the requirement of de novo protein synthesis, as
      demonstrated by anisomycin inhibition of both ionomycin- and CD3-induced CD25
      transcription. Thus, rapamycin inhibition of T cell activation may involve not
      only IL-2-driven proliferation, but also suppression of CD25 up-regulation.

PMID- 8565320
TI  - IL-6-induced anaemia in rats: possible pathogenetic implications for anemia
      observed in chronic inflammations.
AB  - Anaemia of chronic disease (ACD) is frequently found in rheumatoid arthritis
      (RA). In the pathogenesis of ACD both cytokines, such as tumour necrosis factor
      alpha (TNF-alpha), IL-1 and IL-6 as well as a relative deficiency of
      erythropoietin (EPO), are thought to play a key role. In the present study the
      role of IL-6 in the pathogenesis of this anaemia was investigated. IL-6 was
      administered intraperitoneally to rats for 14 sequential days. It appeared that
      IL-6 was able to induce anaemia. No evidence for suppression of bone marrow
      erythropoiesis or enhanced sequestration of erythrocytes in the liver was found.
      However, decreased plasma and bone marrow iron contents were observed in anaemic
      rats. Blood loss in intestinal tissue was demonstrated using erythrocyte
      labelling with 99mtechnetium. Histologically this was associated with
      inflammatory cell infiltration, oedema and bleeding in the intestinal wall. In
      conclusion, IL-6 induced anaemia in rats. This anaemia was caused by intestinal
      blood loss.

PMID- 8565321
TI  - Cytokine-induced differential expression of serum amyloid A genes in fetal and
      neonatal rabbits.
AB  - Serum amyloid A (SAA) is an acute-phase plasma protein which increases 100- to
      1000-fold in response to inflammatory stimuli. In this study pregnant rabbits
      were subjected to laparotomy and their fetuses were injected with
      lipopolysaccharide (LPS) or various cytokines. Newborn rabbits were likewise
      stimulated. Hepatic SAA mRNA was studied using Northern blot analyses and
      scanning densitometry. In vitro derived RNA was used as standard for quantitative
      mRNA analyses. Cytokine concentrations in amniotic fluid and serum were analysed
      by biological assays. Fetal rabbits responded to cytokine stimulation by
      increased hepatic SAA mRNA expression, both during late gestation and in the
      early neonatal period. However, differences in dose-responses, kinetics and mRNA
      concentrations were seen dependent on gestational age. IL-1 and tumour necrosis
      factor (TNF) induced hepatic accumulation of both SAA1, SAA2 and SAA3, while only
      SAA1 and SAA2 mRNA accumulation was seen after IL-6 stimulation. High levels of
      IL-1 and TNF found in amniotic fluid from LPS-stimulated fetal rabbits
      corresponded with high levels in fetal, but not in maternal, serum. High levels
      of IL-1 and TNF, but no IL-6, were seen in newborn control sera and in adult
      serum 1 day after a normal delivery. The study details the complexity of the
      cytokine-induced in vivo response of SAA mRNA in fetal and neonatal rabbits.

PMID- 8565322
TI  - Differential expression of Fc receptors for IgG by monocytes and granulocytes
      from neonates and adults.
AB  - The immature neonatal immune system is thought to result in increased risk of
      infection. Receptors for the Fc moiety of IgG (Fc gamma R) are important in
      antibody-mediated clearance of microbes by granulocytes and
      monocytes/macrophages. As an approach to understanding their role in neonatal
      life, we have compared the constitutive expression of the three Fc receptors--Fc
      gamma RI (CD64), Fc gamma RII (CD32) and Fc gamma RIII (CD16)--by neonatal and
      adult blood monocytes and granulocytes using quantitative immunofluorescence by
      flow cytometry. Our results confirm that there is a small subpopulation of Fc
      gamma RIII-positive monocytes in adult blood, and furthermore show that this is
      absent or at a low percentage in cord blood samples. However, the main population
      of cord blood monocytes expresses low, but significantly higher levels of Fc
      gamma RIII than adult monocytes. No differences were seen in the quantitative
      expression of Fc gamma RI and Fc gamma RII. Neonatal granulocytes expressed
      significantly higher levels of both Fc gamma RI and Fc gamma RII but
      significantly lower levels of Fc gamma RIII. The data are discussed in terms of
      the possible role of cytokines and susceptibility to infection.

PMID- 8565323
TI  - Focus on genome imprinting.

PMID- 8565324
TI  - Genome imprinting: an overview.

PMID- 8565325
TI  - Epigenetic programming of differential gene expression in development and
      evolution.
AB  - This review covers data on changing patterns of DNA methylation and the
      regulation of gene expression in mouse embryonic development. Global
      demethylation occurs from the eight-cell stage to the blastocyst stage in
      preimplantation embryos, and global de novo methylation begins at implantation.
      We have used X-chromosome inactivation in female embryos as a model system to
      study specific CpG sites in the X-linked Pgk-1 and G6pd housekeeping genes and in
      the imprinted regulatory Xist gene to elucidate the role of methylation in the
      initiation and maintenance of differential gene activity. Methylation of the X
      linked housekeeping genes occurs very close in time to their inactivation, thus
      raising the question as to whether methylation could be causal to inactivation,
      as well as being involved in its maintenance. A methylation difference between
      sperm and eggs in the promoter region of the Xist gene, located at the X
      chromosome inactivation centre, is correlated with imprinted preferential
      inactivation of the paternal X chromosome in extra-embryonic tissues. Based on
      our data, a picture of the inheritance of methylation imprints and speculation on
      the significance of the Xist imprint in development is presented. On a more
      general level, an hypothesis of evolution by "adaptive epigenetic/genetic
      inheritance" is considered. This proposes modification of germ line DNA in
      response to a change in environment and mutation at the site of modification
      (e.g., of methylated cytosine to thymine). Epigenetic inheritance could function
      to shift patterns of gene expression to buffer the evolving system against
      changes in environment. If the altered patterns of gene activity and inactivity
      persist, the modifications may become "fixed" as mutations; alternatively,
      previously silenced gene networks might be recruited into function, thus
      appearing as if they are "acquired characteristics." An extension of this
      hypothesis is "foreign gene acquisition and sorting" (selection or silencing of
      gene function according to use). "Kidnapping" and sorting of foreign genes in
      this way could explain the observation that increased complexity in evolution is
      associated with more "junk" DNA. Adaptive epigenetic/genetic inheritance
      challenges the "central dogma" that information is unidirectional from the DNA to
      protein and the idea that Darwinian random mutation and selection are the sole
      mechanisms of evolution.

PMID- 8565326
TI  - Transmission-ratio distortion of X chromosomes among male offspring of females
      with skewed X-inactivation.
AB  - We have begun a search for heritable variation in X-chromosome inactivation
      pattern in normal females to determine whether there is a genetic effect on the
      imprinting of X-chromosome inactivation in humans. We have performed a
      quantitative analysis of X-chromosome inactivation in lymphocytes from mothers in
      normal, three-generation families. Eight mothers and 12 grandmothers exhibited
      evidence of highly skewed patterns of X-chromosome inactivation. We observed that
      the male offspring of females with skewed X-inactivation patterns were three
      times more likely to inherit alleles at loci that were located on the inactive X
      chromosome (Xi) than the active X chromosome (Xa). The region of the X chromosome
      for which this phenomenon was observed extends from Xp11 to -Xq22. We have also
      examined X-chromosome inactivation patterns in 21 unaffected mothers of male
      bilateral sporadic retinoblastoma patients. Six of these mothers had skewed
      patterns of X-chromosome inactivation. In contrast to the tendency for male
      offspring of skewed mothers from nondisease families to inherit alleles from the
      inactive X chromosome, five of the six affected males inherited the androgen
      receptor alleles from the active X chromosome of their mother.

PMID- 8565327
TI  - Genetic conflict and evolution of mammalian X-chromosome inactivation.
AB  - The existence of parentally imprinted gene expression in the somatic tissues of
      mammals and plants can be explained by a theory of intragenomic genetic conflict,
      which is a logical extension of classical parent-offspring conflict theory. This
      theory unites conceptually the phenomena of autosomal imprinting and X-chromosome
      inactivation. We argue that recent experimental studies of X-chromosome
      inactivation and androgenetic development address previously published
      predictions of the conflict theory, and we discuss possible explanations for the
      occurrence of random X-inactivation in the somatic tissues of eutherians.

PMID- 8565328
TI  - Expression of X-linked genes in androgenetic, gynogenetic, and normal mouse
      preimplantation embryos.
AB  - A quantitative RT-PCR approach has been used to examine the expression of a
      number of X-linked genes during preimplantation development of normal mouse
      embryos and in androgenetic and gynogenetic mouse embryos. The data reveal
      moderately reduced expression of the Prps1, Hprt, and Pdha1 mRNAs in androgenetic
      eight-cell and morula stage embryos, but not in androgenetic blastocysts. Pgk1
      mRNA abundance was severely reduced in androgenones at the eight-cell and morula
      stages and remained reduced, but to a lesser degree, in androgenetic blastocysts.
      These data indicate that paternally inherited X chromosomes are at least
      partially repressed in androgenones, as they are in normal XX embryos, and that
      the degree of this repression is chromosome position-dependent or gene-dependent.
      Gynogenetic embryos expressed elevated amounts of some mRNAs at the morula and
      blastocyst stages, indicative of a delay in dosage compensation that may be
      chromosome position-dependent. The Xist RNA was expressed at a greater abundance
      in androgenones than in gynogenones at the eight-cell and morula stages,
      consistent with previous studies. Xist expression was observed in both
      androgenones and gynogenones at the blastocyst stage. We conclude that the
      developmental arrest in early androgenones may be, in part, due to reduced
      expression of essential X-linked genes, particularly those near the X
      inactivation center, whereas the developmental defects of gynogenones and
      parthenogenones, by contrast, may be partially due to overexpression of X-linked
      genes in extraembryonic tissues, possibly those farthest away from the X
      inactivation center.

PMID- 8565329
TI  - Identification of genes showing altered expression in preimplantation and early
      postimplantation parthenogenetic embryos.
AB  - Uniparental embryos have been instrumental in studying imprinting because
      contributions from the parental genomes can be determined unambiguously. In this
      study, we set out to identify imprinted genes showing differential expression
      between parthenogenetic and fertilized embryos during preimplantation and early
      postimplantation stages of development. We identified three genes--apolipoprotein
      E, pyruvate kinase-3, and protein phosphatase 1 gamma--that represent excellent
      candidates for imprinted genes, based on the results of the differential screen,
      their function in differentiation and the cell cycle, and their location within
      imprinted chromosomal regions. In addition, two novel genes expressed in
      trophoblast were identified, 1661 and RA81. These genes, together with four known
      imprinted genes, H19, Igf2r, Igf2, and Snrpn, showed evidence of expression from
      both parental alleles in early stage embryos, indicating a role for
      postfertilization processes in regulating imprinted gene function.

PMID- 8565331
TI  - Imprinting of IGF2, insulin-dependent diabetes, immune function, and apoptosis: a
      hypothesis.
AB  - Parental genomic imprinting is the phenomenon in which the behavior of a gene is
      modified, depending on the sex of the transmitting parent [Peterson and Sapienza
      (1993): Annu Rev Genet 27:7-31]. Recent observations have revealed that the
      inheritance patterns, age-of-onset, severity, and etiology of certain human
      diseases can be explained by aberrations in the establishment or the maintenance
      of the imprint. Examples include the Prader-Willi, Angelman, and Beckwith
      Wiedemann syndromes [Nicholls (1994): Am J Hum Genet 54:733-740], malignancy
      [Sapienza (1990): Biochim Biophys Acta 1072:51-61; Feinberg (1993): Nat Genet
      4:110-113], and insulin-dependent diabetes mellitus (IDDM) [Julier et al. (1994)
      Nature 354:155-159; Bennett et al. (1995) Nat Genet 9:284-292]. We review the
      evidence that implicates an imprinted gene in the INS-IGF2 region of chromosome
      11p15 in the etiology of IDDM (referred to as the IDDM2 locus) and show that in
      human fetal pancreas, INS is not imprinted, thus providing an argument against
      INS as the candidate gene. We also examine imprinting effects on the expression
      of IGF2 in components of the human immune system believed to be important in IDDM
      and show imprinted expression in fetal thymus as early as 15 weeks gestation. We
      demonstrate further that in the circulating mononuclear cells of two individuals,
      lectin-stimulated IGF2 transcription was biallelic, indicating relaxation of
      imprinting, whereas in one individual, transcription was monoallelic. Finally, we
      review the current available data supporting a role for insulin-like growth
      factor-II (IGF-II) in the immune system and, more specifically, discuss the
      evidence supporting a role for the IGFs in the prevention of apoptosis. These
      data have led us to formulate a novel hypothesis that could mechanistically
      explain the involvement of the IDDM2 locus in the pathogenesis of IDDM.

PMID- 8565330
TI  - Chromatin structure and imprinting: developmental control of DNase-I sensitivity
      in the mouse insulin-like growth factor 2 gene.
AB  - The insulin-like growth factor 2 (Igf2) gene on distal mouse chromosome 7 is
      expressed predominantly from the paternal allele. In previous studies we
      identified two regions of paternal allele-specific methylation; one at
      approximately 3 kb upstream of promoter 1, and a second in the 3', coding portion
      of the gene. The 3' region is methylated in an expressing tissue (fetal liver),
      whereas in a non-expressing tissue (fetal brain), it is not methylated. By
      contrast, in the 5' region, the paternal allele is highly methylated in all
      tissues. Here, we have studied another characteristic of chromatin, namely,
      sensitivity to DNase-I and have focused our developmental analysis on the two
      differentially methylated regions of Igf2. In the upstream region, four clustered
      DNase-I hypersensitive sites (HSS) were detected in embryonic stem (ES) cells and
      in midgestation embryos, but not in neonatal liver or brain. In promoter 1 (P1),
      at approximately 0.3 kb upstream of exon 1, we detected a tissue-specific HSS
      that was present in neonatal liver, in which P1 is active, but was absent in ES
      cells, the embryo, and in neonatal brain. No DNase-I HSS were detected in the 3'
      differentially methylated region of Igf2. In all these regions, we did not detect
      differences in DNase-I sensitivity between the parental chromosomes. These
      results establish major developmental and tissue-specific control of chromatin in
      the Igf2 locus. The presence of the HSS upstream of Igf2 precedes transcriptional
      activation of the Igf2 gene and may be indicative of a promoter for another
      transcript that is transcribed in the opposite direction. The HSS in P1 is
      largely liver-specific; this promoter therefore is differently regulated than the
      more general fetal promoters P2 and P3. Whereas methylation can be allele
      specific, presumably reflecting the gene imprint, the nuclease sensitivity, as
      detected by our assay, is not. These results, taken together with previous
      observations, reveal developmental and tissue-specific complexity in the
      expression of the parental imprint at the level of chromatin and transcription.
      We propose that epigenetic features of tissue-specific control and of the control
      of allelic expression are intricately linked.

PMID- 8565332
TI  - Expression of SGP-1 mRNA in preimplantation mouse embryos.
AB  - In a search for genes expressed in preimplantation mouse embryos that are
      important for the earliest steps in differentiation, we identified an abundant
      mRNA that codes for a sulfated glycoprotein, SGP-1. The amount of this RNA rises
      approximately 100-fold during preimplantation development to a level
      approximately equal to that of beta-actin mRNA in blastocysts, although the level
      of these transcripts per cell remains fairly constant during these stages at
      approximately 2,000-4,000 copies. An antisense RNA that is complementary to
      approximately the last one-third of the message and contains an open reading
      frame of 455 nt was found in blastocysts at a 2-3-fold higher level than the
      mRNA. In situ hybridization with sense and antisense riboprobes showed that both
      strands are distributed throughout the embryo. The abundance of the SGP-1 mRNA
      indicates that the encoded protein may play an important role in the development
      of embryos, and the excess of antisense RNA raises the possibility of an unusual
      mechanism of regulating its expression.

PMID- 8565333
TI  - Differential amplification of pheromone genes of the ciliate Euplotes raikovi.
AB  - In hypotrich ciliates, the entire silent chromosomal genome of the germinal
      nucleus (micronucleus) undergoes extensive DNA rearrangements that, during the
      development of the somatic nucleus (macronucleus) at the beginning a new cell
      life cycle, eventually result in the production of linear DNA molecules. These
      molecules represent functional genes, each one consisting of a central coding
      region flanked by two shorter regions, which apparently lack canonical elements
      for regulation of replication and transcription. These are amplified to thousands
      of copies in the "adult" macronucleus of the vegetative cell. We defined the
      extent of this amplification for allelic codominant genes which, in the
      macronucleus of Euplotes raikovi, encode polypeptide cell recognition factors
      (pheromones). This amplification was shown to be allele-specific. The copy
      numbers of genes coding for pheromones Er-1, Er-2, and Er-10 were determined to
      be 2.5-2.9 x 10(4), 0.9-1.2 x 10(4), 1.6-1.85 x 10(4) respectively, and these
      numbers did not appreciably vary during the vegetative cell proliferation. This
      differential amplification of pheromone genes was (i) independent of whether two
      genes coexisted in the same heterozygous cell or were separated in the
      corresponding homozygotes, and (ii) directly correlated with quantitative
      variations in mRNA synthesis and pheromone secretion. On the basis of these
      results, it is suggested that a mechanism of gene-specific amplification may be
      used by hypotrich ciliates to modulate gene expression.

PMID- 8565334
TI  - A Xenopus laevis gene encoding EF-1 alpha S, the somatic form of elongation
      factor 1 alpha: sequence, structure, and identification of regulatory elements
      required for embryonic transcription.
AB  - Transcription of the Xenopus laevis EF-1 alpha S gene commences at the mid
      blastula stage of embryonic development and then continues constitutively in all
      somatic tissues. The EF-1 alpha S promoter is extremely active in the early
      Xenopus embryo where EF-1 alpha S transcripts account for as much as 40% of all
      new polyadenylated transcripts. We have isolated the Xenopus EF-1 alpha S gene
      and used microinjection techniques to identify promoter elements responsible for
      embryonic transcription. These in vivo expression studies have identified an
      enhancer fragment, located approximately 4.4 kb upstream of the transcription
      start site, that is required for maximum expression from the EF-1 alpha S
      promoter. The enhancer fragment contains both an octamer and a G/C box sequence,
      but mutation studies indicate that the octamer plays no significant role in
      regulation of EF-1 alpha S expression in the embryo. The presence of a G/C
      element in the enhancer and of multiple G/C boxes in the proximal promoter region
      suggests that the G/C box binding protein, Sp1, plays a major role in the
      developmental regulation of EF-1 alpha S promoter activity.

PMID- 8565335
TI  - [Nocturnal hypoxia index: a new pulse oxymetry index of nocturnal hypoventilation
      in neuromuscular disorders].
AB  - Respiratory insufficiency due to progressive muscle wasting is a major cause of
      death in various neuromuscular disorders. Morning headache and anorexia leading
      to slowly progressive body weight loss are frequently observed as initial
      symptoms of insufficient ventilation. From our experience nocturnal pulse
      oxymetry is a valuable study to detect early respiratory insufficiency and
      helpful to evaluate the effectiveness of ventilatory assistance, since
      ventilation is more impaired during sleep in early stage of respiratory
      insufficiency. Percent desaturation time (total desaturation time (SaO2 < or =
      90%)/total sleep time) has been used as the most reasonable index of nocturnal
      hypoventilation. The criteria for introduction of nocturnal mechanical
      ventilation is 20% or more in Duchenne muscular dystrophy. Unfortunately, the
      earliest stage of hypoventilation cannot be detected by this index and it is of
      no use in advanced respiratory failure, because this index never exceeds 100% by
      definition. Here we propose a new index for nocturnal hypoventilation, which is
      defined as follows: nocturnal hypoxia index (NHI) = (% time of 95% > or = SaO2 >
      90%) + (% time of 90% > or = SaO2 > 85%) x 2 + (% time of 85% > or = SaO2 > 80%)
      x 3 + (% time of 80% > or = SaO2 > 75%) x 4 + (% time of 75% > or = SaO2 > 70%) x
      5.... This index is good for any stage of respiratory failure, and applicable to
      nocturnal hypoxia of other causes. The criteria for initiating mechanical
      ventilation in DMD can be substituted by "NHI is above 130."

PMID- 8565336
TI  - [A case of biopsy-proven sarcoid meningoencephalitis presented with
      hallucination, nominal aphasia and dementia].
AB  - Here we report a 36-year-old male with sarcoid meningoencephalitis who initially
      presented with hallucination, nominal aphasia and disturbance of consciousness.
      After the onset, his symptoms fluctuated. He had no meningeal signs, and his
      cranial nerves were normal except for bilateral papapilledema. Muscle power and
      tone was normal, and there was no gait disturbance. Deep tendon reflexes were
      slightly exaggerated in lower extremities, but no pathological reflexes were
      noted. There was no impairment in extrapyramidal system, cerebellar system and
      sensory system. The cerebrospinal fluid revealed increased opening pressure, mild
      lymphocytic pleocytosis, slightly decreased glucose, increased protein to 87mg/dl
      and increased IgG index to 1.11. Cerebrospinal fluid culture was negative. Marked
      meningeal thickening and contrast enhancement was shown by CT and MRI. The
      meningeal biopsy demonstrated characteristic sarcoid nodules and confirmed the
      diagnosis of neurosarcoidosis. His manifestations were alleviated by oral
      administration of corticosteroid. Since neurosarcoidosis is a disorder treatable
      with corticosteroid, it is important to consider the possibility of this disorder
      in mind when a patient is presenting with psychiatric manifestations and chronic
      meningitis.

PMID- 8565337
TI  - [A case of chronic progressive radiation myelopathy with cavity formation in the
      thoracic spinal cord].
AB  - A 70-year-old man was admitted to our hospital in March 1994 because of subacute
      progressive paraparesis and sensory impairment below the level of the second
      thoracic (TH 2) spinal cord on the right side. He had received radiation therapy
      (48 Gy) on his neck and mediastinum eight years previously due to adenocarcinoma
      of the right upper lung. Blood chemistry, CT of the spine, bone and gallium
      scintigraphy were unremarkable. In magnetic resonance imaging (MRI) of the
      thoracic cord, the gadolinium (Gd)-enhanced T1-weighted image showed abnormal
      signal intensities from Th 3 to Th 4 of the spine. Myelography revealed no
      abnormalities. Three months later, the patient became a complete spinal man below
      the level of Th 4. Gd-enhanced MRI of the thoracic cord, performed eleven months
      later, showed formation of a spindle-shaped cavity from Th 2 to Th 5 of the spine
      surrounded by a ring-shaped enhanced cord. Chronic progressive radiation
      myelopathy (CPRM) was diagnosed based on these clinical and MRI findings. This
      was a rare case in which MRI-confirmed cavity formation in the spinal cord
      appeared in a patient with CPRM.

PMID- 8565338
TI  - [Familial myopathy associated with tubular aggregates--report of two siblings].
AB  - We reported two siblings with slowly progressive muscle weakness in proximal and
      peroneal muscles without atrophy, myalgia, cramps, or episodic weakness. The
      serum creatine kinase level was moderately elevated. The prominent features of
      their muscle pathology were accumulation of tubular aggregates in type 2 fibers,
      predominantly in type 2B fibers, and marked type 1 fiber atrophy. Three to eleven
      % of muscle fibers contained tubular aggregates. Electron microscopic examination
      revealed accumulation of double-walled tubular structures. Familial myopathy with
      tubular aggregates as a hallmark of muscle pathology is considered to be a new
      clinical form of childhood-onset familial myopathies.

PMID- 8565339
TI  - [Epilepsia partialis continua with an epileptic focus demonstrated by PET and
      unique MRI findings: report of a case].
AB  - We reported a 31-year-old woman with epilepsia partialis continua (EPC) whose
      epileptic focus was delineated by PET. Neurologic examination revealed EPC in the
      face around the corner of her mouth, her thumb and forefinger on the left, slight
      exaggeration in the left biceps brachii reflex, and the digiti quiniti sign on
      the left. Laboratory tests showed pancytopenia, positive anti-nuclear and anti
      DNA antibodies and decreased levels of serum complements, being consistent with
      systemic lupus erythematosus (SLE). Electroencephalogram showed paroxysmal
      discharges over the right frontoparietal region. PET with 2-18F-fluoro-2-deoxy-D
      glucose (FDG) clearly demonstrated a hypermetabolic area in the right
      frontoparietal cortex. T2-weighted images in MRI revealed reversible high signal
      intensity area in the right insula, postcentral gyrus and angular gyrus, while
      there were no abnormal findings in T1-weighted images with or without Gd-DTPA.
      There are only a few reports of EPC with the epileptic focus delineated by PET.
      Since a focal increase in glucose metabolism observed in them as well as in the
      present patient is a consistent indicator of the epileptic focus, the PET study
      is likely to provide significant information available not only for the diagnosis
      but also for the treatment of the condition. Finally, to our knowledge, this is
      the first patient with SLE presenting EPC. It is important to realize that
      vasculopathy associated with SLE may cause EPC and brain lesions with reversible
      high signal intensities shown by MRI.

PMID- 8565340
TI  - [A diabetic patient with bilateral carotid stenosis who developed neovascular
      glaucoma following cataract surgery].
AB  - A 67-year-old diabetic man suffered from right neovascular glaucoma following the
      ipsilateral cataract surgery. Three years later, he underwent left cataract
      surgery and again developed left neovascular glaucoma after the operation.
      Fluorescein angiogram showed a marked delay in retinal circulation. Moreover,
      severe stenosis of bilateral carotid origins and reflux of bilateral ophthalmic
      arteries were ascertained by neurosonographical examination such as duplex
      cervical echography and transcranial Doppler, as well as an angiogram. Brain
      imaging demonstrated asymptomatic watershed infarction in the left parieto
      occipital cortex. Chronic ocular ischemia caused by carotid stenosis is one of
      the decisive risk factors for secondary glaucoma after cataract surgery.
      Preoperative neurosonographical screening tests are required to decrease ocular
      surgery complications, especially in the aged, and diabetic patients.

PMID- 8565341
TI  - [A case of central retinal artery occlusion followed by cerebral infarction due
      to internal carotid artery disease].
AB  - Reported is a 68-year-old male with left central retinal artery occlusion (CRAO)
      followed by cerebral infarction due to left internal carotid artery disease. He
      was referred to our hospital diagnosed as having left CRAO. In view of severe
      stenosis of ipsilateral internal carotid artery by ultrasound duplex scan,
      carotid endarterectomy (CEA) was indicated. While waiting for the operation, he
      suffered from monoparesis in his right lower limb despite the administration of
      antiplatelet agents. Brain MRI showed cerebral infarction in the left frontal
      cortex. It was suggested that artery-to-artery embolism from the lesion of the
      internal carotid artery might be the common mechanism of CRAO and cerebral
      infarction in this case. According to theses results, CEA should be considered in
      patients with severe stenosis of the internal carotid artery before it is too
      late.

PMID- 8565342
TI  - [Familial amyloidosis of the Finnish type (FAP) with extraocular muscle
      involvement].
AB  - Among 17 patients with amyloid polyneuropathy type IV in a Japanese family, we
      found a 72-year-old woman, who showed extraocular symptoms approximately 10 years
      after the onset of the disease. she developed weakness of the right facial
      muscles and dysarthria at age 57. She had atrophy and disturbance of movement of
      the tongue, along with difficulty in swallowing at age 62. At the age of 66, she
      felt diplopia when she looked toward the left, followed by difficulty of ocular
      movement. These manifestations progressed and at age 72, she was found to have
      mild ptopsis, mild to moderate disturbance of almost all extraocular muscles,
      moderate to severe disturbance of facial, masseter, pharyngeal, tongue and neck
      muscles. She also had slight weakness and atrophy of the limb and truncal muscles
      together with slight loss of pain and vibratory sensations in the distal parts of
      the limbs. FAP IV has sometimes been called cranial amyloidosis, but motor
      disturbance is limited to the middle and lower cranial nerve territories in the
      majority of the reported cases, and manifestations of the extraocular muscles are
      quite rare. According to the present investigation of the world literature, this
      is the second case of FAP IV with extraocular muscle involvement.

PMID- 8565343
TI  - [Anterior nerve roots enhancement on MRI in a case of Guillain-Barre syndrome].
AB  - A 4-year-old girl with Guillain-Barre syndrome (GBS) showed the abnormal
      enhancement on MRI in the anterior nerve roots corresponding to the region of her
      muscle weakness on the 26th day of illness. The enhancement on MRI almost
      disappeared on the 89th day of illness, when her symptoms had more improved. We
      think that enhanced spinal MRI is useful to reveal the involved nerve roots and
      the degree of the illness in GBS.

PMID- 8565344
TI  - [A case of dissecting aneurysm of the basilar artery presented as superior pons
      type of Foville's syndrome].
AB  - Here we report a 47-year-old man with dissecting aneurysm of the basilar artery
      who developed Foville's syndrome due to upper pons involvement. At first he had
      an abrupt onset of dysarthria and weakness in his left upper and lower
      extremities during his work. Neurological examination on admission revealed mild
      disturbance of consciousness, absent light reaction on the left side, hypesthesia
      of the left face, absent gag reflex, dysarthria, and left hemiparesis with
      ataxia. On the second hospital day he developed paralysis of conjugate eye
      movement to the right, left central facial palsy, and left hemiplegia, and
      hyperhidrosis of the left side of the body. He was diagnosed to have superior
      pons type of Foville's syndrome. Computed tomography showed low density area in
      the right upper pons, and the basilar artery had marked lateral shift,
      dilatation, and calcification. Vertebral angiography demonstrated dissecting
      aneurysm of the basilar artery. Although it is very rare that dissecting aneurysm
      of the basilar artery causes the brain stem symptoms, its possibility should be
      considered when computed tomography shows marked lateral shift, dilatation,
      and/or calcification of the basilar artery.

PMID- 8565345
TI  - [An adult case of bacterial meningitis caused by penicillin-resistant
      Streptococcus pneumoniae].
AB  - Recently the incidence of infectious diseases caused by penicillin-resistant
      Streptococcus pneumoniae (PRSP) is increasing. Patients with meningitis caused by
      PRSP have been reported with high mortality especially in the field of
      pediatrics, and it is crucial to treat with accurate and precise choice of
      antibiotics. We report the first adult case of bacterial meningitis caused by
      PRSP in Japan. A 32-year-old male without immunological abnormalities developed
      acute pneumococcal meningitis. Empiric therapy with ampicillin and cefotaxime was
      not effective and the S. pneumonia from CSF showed resistance to multiple
      antibiotics such as penicillin and cefotaxime. He was treated successfully with
      the combination of panipenem/betamipron, vancomycin, and chloramphenicol. We
      assume that panipenem/betamipron is recommended to be added to empiric therapy of
      bacterial meningitis, considering an increasing incidence of PRSP infection.

PMID- 8565346
TI  - [Mononeuropathy multiplex in a patient receiving interferon alpha therapy for
      chronic hepatitis C].
AB  - We report a case of mononeuropathy multiplex due to interferon alpha (IFN alpha)
      therapy for chronic hepatitis C. A 61-year-old man received IFN alpha (natural
      type 6 x 10(6) IU), every day for two weeks and three times a week for 22 weeks
      by intramuscular injection. Seventeen weeks after the initiation of IFN alpha
      therapy, he noticed painful dysesthesia, muscle weakness and muscular atrophy of
      the left lower extremity. Neurological examination revealed weakness of the left
      iliopsoas, quadriceps femoris and femoral adductor muscles, hypesthesia and
      dysesthesia. Electromyogram showed neuropathic change in the left vastus
      lateralis muscle. Muscle computed tomography showed muscular atrophy of the left
      lower extremity. Two months after discontinuation of the IFN alpha therapy,
      dysesthesia and muscle weakness of the left lower extremity improved
      spontaneously. He was diagnosed as mononeuropathy multiplex of the left femoral
      nerve and obturator nerve caused by IFN alpha therapy. Attention must be paid to
      dysesthesia, muscle weakness and muscular atrophy when IFN alpha therapy is
      initiated.

PMID- 8565347
TI  - [A case of rhabdomyolysis complicated with myocardial injury].
AB  - A 22-year-old man developed transient unconsciousness during running. He
      developed fever, nausea, vomiting, diarrhea and general fatigue. Next day, he was
      admitted to National Hospital Nayoro because of high serum CK level of 13,610U/l.
      Biochemical analyses revealed elevated serum myoglobin, increased CK-MM isozyme,
      aldolase and lactate dehydrogenase, increased serum osmolality, increased uric
      acid, and decreased serum potassium levels. Therefore, he was diagnosed as having
      rhabdomyolysis. In addition, serum CK-MB isozyme, cardiac myosin light chain I
      and troponin T were increased, suggesting the damage of cardiac muscle.
      Electrocardiogram showed elevated ST segment and inverted T on V2-4, which were
      not observed previously. He had no preceding infectious disease, drug ingestion
      or an underlying metabolic disorder. The rhabdomyolysis may be precipitated by
      the superimposition of dehydration and loss of potassium due to diarrhea and
      vomiting. The myocardial injury, probably produced by transient myocardial
      ischemia, should be paid attention in case of rhabdomyolysis.

PMID- 8565348
TI  - [A case of transient ischemic attacks preceded by postprandial hypotension].
AB  - A 78-year-old man with a history of total gastrectomy, myocardial infarction and
      hypertension was admitted to our hospital because of frequent transient attacks
      of consciousness disturbance, aphasia and right hemiparesis after meals. His
      attacks occurred one to three times a day, 30 to 60 minutes after meals and
      lasted 120 to 180 minutes. At the time of the attacks his blood pressure
      decreased, but his pulse rate did not change. Cerebral angiography demonstrated
      atherosclerotic occlusion of the left internal carotid artery. There was no
      myocardial uptake of 123I-metaiodobenzylguanidine (MIBG). These results suggest
      that our patient had an autonomic dysfunction. Duplex carotid ultrasonography
      revealed that the blood flow velocity fell about 30% at the time of the attacks.
      His autonomic dysfunction and major artery occlusion may have produced a
      hemodynamic TIA following postprandial hypotension.

PMID- 8565349
TI  - [Frontal type adrenoleukodystrophy: the progress of the white matter lesion--a
      neuroradiological and pathological study].
AB  - We studied the correlation between neuroradiological findings and pathological
      observations of white matter lesions in a patient with frontal type
      adrenoleukodystrophy. A 41-year-old man developed schizophrenic symptoms and
      generalized convulsions at the age of 40. Examination revealed baldness, loss of
      the axillary hair, stereotypical behavior, mutism, dysphagia echographia, right
      hemiparesis, and brisk reflexes in all four limbs with bilateral extensor plantar
      responses. Blood examination revealed a high concentration of very-long-chain
      fatty acids in plasma; the patient was diagnosed as having adrenoleukodystrophy.
      His condition continued to worsen, and gradually he became akinetic. He died of
      pneumonia at the age of 43. T1- and T2-weighted MR images distinguished three
      abnormal zones in the cerebral white matter in this case. In the first zone (Z1),
      the signal intensity was moderately high on T2-weighted images and slightly low
      on T1-weighted images; this zone was not enhanced with Gd-DTPA. In the second
      zone (Z2), the signal intensity was slightly high on T2-weighted images, while
      moderately low on T1-weighted images; Z2 was enhanced with Gd-DTPA. In the third
      zone (Z3), the signal intensity was markedly high on T2-weighted images and low
      on T1-weighted images; Z3 was not enhanced with Gd-DTPA. Z3 was located in the
      frontal pole; Z2 and Z1 were consecutively located in rostro-caudal fashion in
      the brain. The subsequent pathological study of the brain of this patient
      revealed the following findings: Z1 showed destruction of myelin with axonal
      sparing, Z2 showed numerous lipid-laden macrophages, demyelinated axons, and a
      vigorous perivascular mononuclear cell response, Z3 consisted of a dense mesh of
      glial fibrils and scattered astrocytes without any evidence of an active process.
      In this study, the correlation between MR images and pathological findings in
      adrenoleukodystrophy was clearly established. Single photon emission tomography
      with 99mTc-hexamethylpropyleneamine oxime, and positron emission tomography with
      15O2 continuous inhalation technique showed a reduction in the regional cerebral
      blood flow (rCBF) and in the regional cerebral metabolic rate of oxygen (rCMRO2)
      in the cerebral cortex near the Z1 and Z3. A normal or slight increase of rCBF
      and a reduction of r CMRO2 was found in the cerebral cortex near the Z2. Coronal
      MR images showed that Z3 was located in the deep white matter, while Z2 and Z1
      were consecutively located in an inner-outward fashion, suggesting that the
      demyelination process started in the cingulum and spread in an inner-outward
      fashion and progressed in rostro-caudal manner.

PMID- 8565350
TI  - [The high-dose gamma-globulin therapy for inflammatory demyelinating peripheral
      neuropathy: evaluations of clinical effects and serum IgG subclasses].
AB  - PURPOSE OF THE STUDY: To clarify the clinical effects and the influence of high
      dose therapy of gamma-globulin for inflammatory demyelinating peripheral
      neuropathy, we have investigated changes of serum IgG subclass distribution of
      the patients with these diseases by this therapy. SUBJECTS AND METHODS: gamma
      Globulin (20g/day) was intravenously administrated for 5 days in 4 cases of CIDP,
      2 cases of Fisher syndrome and 1 case of Guillain-Barre syndrome. The IgG
      subclass was measured by sandwich ELISA method four times, namely before the
      treatment, immediately after, and 2 and 4 weeks after the treatment. RESULTS:
      Marked symptomatical improvement was observed in all cases. Serum levels of all
      IgG subclasses were highest just after the therapy, and all subclasses recovered
      to the pretherapeutic levels in 4 weeks. Attitude of changes in all IgG
      subclasses of all cases was fairly similar each other. CONCLUSION: These results
      suggest that high-dose therapy of gamma-globulin is an effective therapy for
      inflammatory demyelinating peripheral neuropathy with little influences on IgG
      production and metabolism of IgG.

PMID- 8565351
TI  - [Expression of MHC and cell adhesion molecules in muscular sarcoidosis].
AB  - Biopsied skeletal muscles from 5 patients with muscular sarcoidosis (nodular
      type; 1, and myopathic type; 4) were immunocytochemically examined. All biopsies
      presented granulomatous changes. Atrophic or regenerating muscle fibers adjacent
      to granuloma demonstrated compression or ischemic changes. In the center of the
      granuloma, CD68+ epitheloid cells and giant cells, and CD4+ T cells were
      localized. At the periphery of the granuloma, CD4+ T cells, CD8+ T cells, CD20+ B
      cells, and CD68+ macrophages were found. Expression of HLA-A,B,C was diffuse in
      the muscle fibers. Expression of HLA-DR and ICAM-1 was more prominent near the
      granuloma or perifascicular fibers, and that of LFA-3 was moderate in those
      lesions. VCAM-1 was expressed in endothelial cells and macrophages near the
      granuloma. Those findings indicate that interferon-gamma or TNF-alpha produced by
      infiltrating inflammatory cells may induce expression of these immunologic
      markers or adhesion molecules. Immunocytochemical differences between the nodular
      and myopathic forms of sarcoidosis are not evident, but either localization or
      abundance of granuloma in muscle bulks is relevant to weakness or atrophy of
      clinically affected muscle.

PMID- 8565352
TI  - Localization of Tc-99m sestamibi and TI-201 in an unsuspected calcified
      intrathoracic mass.
AB  - Tc-99m MIBI and TI-201 uptake have been reported in benign and malignant lesions.
      However, concordant uptake of both radiotracers has been described infrequently.
      The authors report a patient with a case history of tuberculosis and breast
      cancer who underwent a TI-201 cardiac stress/planar study initially for
      complaints of angina pectoris, and 3 years later a follow-up Tc-99m MIBI cardiac
      study was completed for similar complaints. These studies incidentally revealed
      uptake of TI-201 and Tc-99m MIBI in a large left lung mass unchanged in size
      between the two studies. CT with intravenous contrast performed 2 months after
      the Tc-99m MIBI study revealed a 9 cm calcified soft-tissue mass in the left lung
      with adjacent pleural calcifications.

PMID- 8565353
TI  - Diagnosis of uterine abnormalities with radionuclide imaging.
AB  - A pelvic hypervascular blush often creates a diagnostic dilemma during
      radionuclide abdominal imaging studies in females. This blush is shown to be due
      to uterine vascularity that is more prominent in the secretory and menstrual
      phases of the menstrual cycle. Significant uterine vascularity in the earlier
      phases is inappropriate and may be pathologic. Three such cases are presented in
      which increased uterine vascularity on radionuclide imaging during the
      proliferative phase either lead to a diagnosis or supported a clinical finding.

PMID- 8565354
TI  - Metastatic pleural cancer in radionuclide angiocardiography. A pulmonary time
      activity curve mimicking left-to-right cardiac shunt.
AB  - A 55-year-old man, with a history of nephrectomy for renal cell carcinoma, was
      evaluated using radionuclide angiocardiography to exclude cardiac shunts as the
      cause of vascular bruits heard at auscultation. A pulmonary time-activity curve
      derived from the right lung showed a pattern typical of a large left-to-right
      shunt, whereas that from the left lung was normal. Increased systemic arterial
      flow to the lateral right chest was noted in early dynamic images. Subsequent
      studies revealed that this flow and the abnormal time-activity curve of the right
      lung were due to systemic arterial supply to metastatic pleural cancer,
      originating from the kidney. The authors conclude that special caution should be
      undertaken in the interpretation of the radionuclide angiocardiography for
      determining left-to-right cardiac shunts, especially in those showing a
      asymmetric pulmonary time-activity curve.

PMID- 8565355
TI  - The visualization of pulmonary tuberculosis with Tc-99m (V) DMSA and Tc-99m
      citrate in comparison to Ga-67 citrate.
AB  - Two patients with active tuberculosis confirmed by chest radiography and positive
      sputum smears were included in this study to determine whether a Tc-99m labeled
      agent, such as DMSA or citrate could localize such lesions in comparison to Ga-67
      citrate. Both patients had Tc-99m (V) DMSA, Tc-99m citrate, and Ga-67 citrate
      scanning at 1-day to 5-day intervals. Both patients had positive scan findings
      with all three radiopharmaceuticals. However, the quality of Tc-99m (V) DMSA
      scans was superior to Tc-99m citrate, which showed faint uptake. Tc-99m (V) DMSA
      may be a better alternative to Ga-67 citrate in the assessment of the activity
      and extent of tuberculosis.

PMID- 8565356
TI  - Pericardial effusion demonstrated by I-123 MIBG.

PMID- 8565357
TI  - Clinically silent pulmonary embolism due to transient protein S deficiency.

PMID- 8565358
TI  - Tc-99m MDP detection of diffuse metastatic involvement of the liver by salivary
      gland mucoepidermoid carcinoma.

PMID- 8565359
TI  - Scintigraphic "doughnut sign" on bone scintigraphy secondary to metastatic
      hepatocellular carcinoma.

PMID- 8565361
TI  - Greatly increased humeral uptake as a sign of leukemia.

PMID- 8565360
TI  - Tc-99m pertechnetate scrotal imaging of an inguinal hernia simulating testicular
      inflammation.

PMID- 8565362
TI  - Pineoblastoma imaged during bone scintigraphy.

PMID- 8565363
TI  - Tc-99m pertechnetate accumulation in osteotomy site.

PMID- 8565364
TI  - Pericardial and mediastinal involvement from bronchogenic carcinoma demonstrated
      by Tl-201 imaging.

PMID- 8565365
TI  - Recurrent pulmonary embolism and chronic multivessel thrombophlebitis associated
      with a right-to-left shunt in the antiphospholipid syndrome.

PMID- 8565366
TI  - Brain SPECT in Wilson's disease.

PMID- 8565368
TI  - Delayed restoration of lung perfusion after removal of aspirated foreign body.

PMID- 8565367
TI  - Perforated peptic ulcer demonstrated by biliary imaging.

PMID- 8565369
TI  - Scintigraphic findings in a case of lymphangioleiomiomatosis.

PMID- 8565370
TI  - Scintigraphic demonstration of hemangioma in neck.

PMID- 8565371
TI  - Tc-99m MIBI accumulation in remnant thymus: the cause of false-positive
      interpretation in parathyroid imaging.

PMID- 8565372
TI  - Current readings in nuclear medicine.

PMID- 8565373
TI  - Feasibility of Meckel's scan after RBC gastrointestinal bleeding study using in
      vitro labeling technique.
AB  - The authors report a successful Meckel's scan performed 26 hours after a labeled
      RBC study using a commercial in-vitro labeling kit, UltraTag (Mallinckrodt
      Medical, Inc., St. Louis, MO). No abnormal alteration of Tc-99m distribution was
      observed as would be seen if an in-vivo RBC labeling technique was used. This
      case demonstrates that it is feasible to perform an in-vitro labeled RBC study
      for acute gastrointestinal bleeding in pediatric patients and to follow-up with a
      Meckel's scan if it is necessary for diagnostic confirmation.

PMID- 8565374
TI  - Hepatobiliary clearance of intravenous Tc-99m pertechnetate.
AB  - The normal biodistribution of Tc-99m pertechnetate includes the thyroid gland,
      salivary glands, choroid plexus, and gastric mucosa. The primary route of
      excretion is through renal clearance. The authors describe two cases in which
      hepatobiliary excretion of intravenously administered Tc-99m pertechnetate was
      observed during scanning for Meckel's diverticulum as a possible source of
      gastrointestinal bleeding.

PMID- 8565375
TI  - Importance of the lateral view in the evaluation of suspected brain death.
AB  - The authors present two cases of clinical brain death that failed to meet the
      criteria for whole brain death using Tc-99m HMPAO. Conventional anterior cerebral
      flow studies demonstrated no intracerebral perfusion. Anterior static images also
      failed to show cerebral activity. However, the lateral images clearly demonstrate
      cerebellar activity. These cases demonstrate the importance of Tc-99m HMPAO as
      the agent of choice in evaluating brain death and the necessity of lateral views
      to meet the criteria for whole brain death. Cerebellar perfusion challenges the
      present criteria for whole brain death. New criteria must re-evaluate the present
      technology.

PMID- 8565376
TI  - Diagnosing protein losing enteropathy. A new approach using Tc-99m human
      immunoglobulin.
AB  - Tc-99m HIG has recently come into prominence as an inflammation seeking
      radiotracer. The authors describe a novel use of the agent for imaging protein
      losing enteropathy. The agent may have certain advantages over Tc-99m HSA, which
      is currently being used for imaging protein loss.

PMID- 8565377
TI  - Avid In-111 labeled WBC accumulation in a patient with active osteoarthritis of
      both knees.
AB  - An In-111 WBC study showed intense periarticular uptake in both knees of a
      patient being investigated to exclude joint infection before total knee
      replacement surgery for advanced osteoarthritis. Infection was subsequently
      excluded. Patients with synovitis secondary to active osteoarthritis can have
      intense synovial uptake of labeled WBCs. This should be considered as a cause of
      false-positive scans in the investigation of septic arthritis with labeled WBCs.

PMID- 8565378
TI  - Intense gallbladder uptake associated with chemotherapy. An unusual finding in
      pediatric skeletal scintigraphy.
AB  - Focal and diffuse hepatic uptake of bone-seeking radiopharmaceuticals may be due
      to a variety of conditions including tumors and radiopharmaceutical impurity.
      However, uptake in the gallbladder is unusual with currently used skeletal
      agents. Three patients (aged 10, 15, and 16 years) underwent routine whole-body
      bone scans during a course of intensive chemotherapy with VP-16 and ifosphamide.
      Images showed intense gallbladder and faint liver uptake. No patient had symptoms
      of cholecystitis. Radiopharmaceutical quality control revealed no impurities.
      Repeat bone scans after completion of chemotherapy showed no liver or gallbladder
      uptake. The authors conclude that this finding represents altered distribution
      induced by the chemotherapy regimen, and should not be misinterpreted as
      intrinsic liver or gallbladder disease.

PMID- 8565380
TI  - Localized manifestations of subacute thyroiditis presenting as solitary transient
      cold thyroid nodules. A report of 11 patients.
AB  - Eleven patients, each with a painful solitary cold nodule of the thyroid were
      evaluated. All patients had subacute thyroiditis associated with neck pain and
      tenderness. Despite elevated sedimentation rate and increased thyroglobulin
      levels, nine of the patients were euthyroid, and I-131 uptake was normal in six.
      In all patients, thyroid scintigraphy demonstrated a solitary cold nodule that
      resolved regardless of anti-inflammatory therapy. Granulomatous subacute
      thyroiditis is characterized by decreased I-131 uptake accompanied by transient
      hyperthyroidism. The uncommon localized variant of this entity may present with a
      painful solitary nodule, normal or only moderately decreased I-131 uptake, and
      should be suspected even in euthyroid patients.

PMID- 8565379
TI  - False-positive imaging of In-111 labeled monoclonal antibody conjugate CYT-103 in
      a patient with metastatic colorectal carcinoma.
AB  - In-111 satumomab whole-body imaging is used in the evaluation of patients with
      colorectal carcinoma. The authors report a case of false-positive In-111
      localization in a nonfunctional adrenal adenoma in a patient with metastatic
      colon carcinoma.

PMID- 8565381
TI  - A patient with an autonomously functioning thyroid nodule with papillary
      adenocarcinoma associated with Graves' hyperthyroidism.
AB  - A 69-year-old man had concomitant findings of an autonomously functioning thyroid
      papillary adenocarcinoma and Graves' hyperthyroidism. The patient presented with
      hyperthyroidism and a right lobe thyroid nodule that was shown to be
      hyperfunctional on I-123 imaging. The TI-201 imaging showed uptake confined
      almost entirely to the right lobe nodule. Papillary adenocarcinoma in the nodule
      and diffuse hyperplasia surrounding the nodule along with a slightly enlarged
      left lobe were found at surgery.

PMID- 8565382
TI  - Inferior vena cava obstruction and diffuse hepatic uptake on lower extremity
      radionuclide venogram.
AB  - Two patients with dissimilar but advanced malignancies and lower extremity
      swelling underwent bilateral lower extremity radionuclide venograms, several
      months apart. Both patients' scintigrams showed multiple collaterals in the
      abdomen and pelvis, consistent with inferior vena cava obstruction, and hepatic
      uptake in a diffuse pattern. One patient also had multiple bilateral pulmonary
      emboli on a lung scan. Although diffuse hepatic uptake has been mentioned before
      with inferior vena cava obstruction, it has usually been incidental to focal
      hepatic uptake near the porta hepatis. The case results in this study
      demonstrated that inferior vena cava obstruction can manifest itself solely as
      diffuse hepatic uptake on nuclear venograms. The authors believe that either
      pattern can be corroborative of inferior vena cava obstruction on a nuclear
      venogram.

PMID- 8565383
TI  - Ga-67 used to localize the tumor bed for radiation therapy after lumpectomy.
AB  - The authors present a new method to locate the tumor bed after lumpectomy. The
      method relies on accumulation of Ga-67 at the surgical site. This technique was
      useful in identifying the tumor bed in six candidates for breast conserving
      surgery and radiation therapy. This method may be applicable in other soft tissue
      malignancies that require postoperative radiation.

PMID- 8565384
TI  - Use of Ga-67 imaging in diagnosis and follow-up after steroid treatment of
      retroperitoneal fibrosis.
AB  - Retroperitoneal fibrosis is an entity with an unknown cause. It is characterized
      by symptoms associated with the gradual compression of the retroperitoneal
      structures. This case report demonstrates the use of Ga-67 imaging in the early
      noninvasive diagnostic work-up and follow-up evaluation of poststeroid therapy.

PMID- 8565385
TI  - Ga-67 and Tc-99m (V) DMSA imaging in non-Hodgkin's lymphoma with amyloid tumor.
AB  - This report describes the localization and categorization of tumors using Ga-67
      and Tc-99m (V) DMSA imaging in a rare case of non-Hodgkin's lymphoma associated
      with an amyloid tumor. Ga-67 uptake was found in both the lymphoma and the
      amyloid tumor. Significant Tc-99m (V) DMSA uptake was found only in the amyloid
      tumor. In this case, Ga-67 uptake was nonspecific, but Tc-99m (V) DMSA uptake
      gave additional information before treatment.

PMID- 8565386
TI  - Behavioral management of children's seizure activity. Intervention guidelines for
      primary-care providers.
AB  - We present behavioral treatment guidelines, based on empirically established
      behavioral interventions, for pediatric paroxysmal disorders. The guidelines
      include affirming the disability and normalizing the role of the environment;
      teaching the child anticonvulsant coping behaviors; giving caregivers guidelines
      to encourage independent functioning; and involving teachers and other
      supervising adults in treatment. The guidelines were developed for economic
      feasibility, time efficiency, and easy execution in any primary-care clinic. A
      patient report demonstrates significant reduction in drug-refractory seizures in
      an 11-year-old girl by implementing the guidelines. Discussion is provided on
      effective implementation of the behavioral guidelines in the primary-care clinic.

PMID- 8565387
TI  - Long-term follow-up of medically treated childhood constipation.
AB  - We describe the long-term (mean 6.8 years) follow-up of 43 children treated
      medically for chronic constipation and encopresis. Overall outcome was quite
      good. Thirty children (70%) were entirely asymptomatic at follow-up. Intermittent
      mild constipation persisted in 13 patients; only two required persistent but
      infrequent laxative therapy. Encopresis persisted in three of 17 children who
      initially reported this symptom, and was associated with significant behavioral
      problems.

PMID- 8565388
TI  - Social factors associated with behavioral problems in children with asthma.
AB  - The objective of this study was to describe the proportion of children with a
      behavior problem and examine which independent variables are associated with the
      presence of a behavior problem in a group of 392 inner-city children with asthma.
      Data on child asthma symptoms, medication use, health-care utilization, and
      school absences were obtained from the parent during a structured telephone
      interview. Included in the interview was a measure of behavior problems and
      social support questions. Children classified with a high level of asthma
      symptoms were more than twice as likely to experience a behavior problem than
      children classified with a low level of asthma symptoms (P = 0.002). Use of
      theophylline medication was not correlated with behavior problems (P = 0.45).
      Significant variables were low level of social support and high or moderate level
      of asthma symptoms. We have identified a group of children at risk for behavior
      problems, specifically in families that lack adequate social and financial
      resources.

PMID- 8565389
TI  - Recognition and management of teething diarrhea among Florida pediatricians.
AB  - According to current medical opinion, teething diarrhea (TD) is a myth; yet cross
      cultural data document a worldwide distribution of popular belief in the
      association of frequent, loose stools with tooth eruption. A mail survey in 1990
      of 215 pediatricians practicing in Florida investigated beliefs and practices
      related to TD. Thirty-five percent of respondents believed there is a real
      association between diarrhea and tooth eruption. When compared with pediatricians
      who do not believe in TD, these respondents were more likely to be more recent
      graduates of medical school, to be in general pediatric practice, to be female,
      to see more patients per week, and to practice in metropolitan areas. The most
      common explanations for the link between dentition and diarrhea were changes in
      eating habits, increased salivation, and stress. Respondents reported that both
      they and the parents of their patients tended to view TD as less serious than
      other types of diarrhea, and both managed it accordingly. When compared with
      earlier studies, our findings indicate that belief in TD among pediatricians may
      have increased since the 1970s. The results suggest a need for more empirical
      research on the effects of tooth eruption on bowel function.

PMID- 8565390
TI  - Patient-triggered ventilation in the newborn.

PMID- 8565391
TI  - Delay in diagnosis of congenital adrenal hyperplasia in an acutely ill infant.
      The confounding effect of unrelated medical therapies.

PMID- 8565392
TI  - Pediatric AIDS with severe T-cell depression and hypogammaglobulinemia.

PMID- 8565393
TI  - Management of the child presenting with allergy to multiple foods.

PMID- 8565394
TI  - Propionic acidemia presenting as pyloric stenosis.

PMID- 8565395
TI  - A computer program for managing lead poisoning in children.

PMID- 8565396
TI  - Congenital malaria: not rare and maybe not resistant.

PMID- 8565397
TI  - Isolated bicuspid aortic valve in a newborn with Down syndrome.

PMID- 8565398
TI  - Noonan and Williams syndromes--basic differential diagnosis.

PMID- 8565399
TI  - More on circumcision.

PMID- 8565400
TI  - How to implement an asthma education program.
AB  - Given that poor asthma management leads to such devastating rates of morbidity
      and mortality in this country, efforts must be made to increase the knowledge,
      skills, and behaviors of persons with asthma. The suggestions and recommendations
      provided here represent a blend of academic opinion and practical advice on
      methods to implement an asthma education program. In developing an asthma
      education program, consideration must be given to what content should be
      included, how and by whom that content should be taught, and when education
      should take place. The identification of a key clinical staff member to take the
      lead in translating these and other asthma education guidelines will be a
      critical next step for clinicians committed to developing an effective asthma
      education program.

PMID- 8565401
TI  - Physiologic diagnosis and function in asthma.
AB  - Asthma is a condition in which there is airway hyperresponsiveness, with the
      propensity for widespread, reversible airways narrowing on exposure to diverse
      inciting factors (triggers). Inhalation of nonspecific agents such as
      methacholine or histamine leads to bronchoconstriction in most cases, and in
      some, the bronchoconstriction follows exposure to specific agents such as antigen
      or occupational irritants. Chest tightness and cough, which are the most common
      symptoms of asthma, are probably the result of inflammation mucus plugs, edema,
      or smooth muscle constriction in the small peripheral airways. Because major
      obstruction of the peripheral airways can occur without recognizable increases of
      airway resistance or FEV1, the physiologic alterations in acute exacerbations are
      generally subtle in the early stages. Poorly ventilated alveoli subtending
      obstructed bronchioles continue to be perfused, and as a consequence, the P(A
      a)O2 increases and the PaO2 decreases. At this stage, ventilation is generally
      increased, with excessive elimination of carbon dioxide and respiratory
      alkalemia. In the more severe exacerbation, lung volume is increased and the
      static volume-pressure curve is shifted up (lung volume is greater) and to the
      left (pressure is lower) while the shape of the curve is unaltered. The airway
      obstruction is reversible and there is generally improvement in air flow rates
      following administration of beta-agonists and anti-inflammatory agents. The
      changes in mechanical properties are also reversible, and therapeutic
      intervention usually results in a shift of the PV curve downward toward the
      normal position, for example, a decrease in TLC and an increase in the elastic
      recoil pressure at any particular lung volume. Failure to take these changes into
      account may underestimate the impact of therapy. The PaO2 decreases (and the P(A
      a)O2 increases) as the work of breathing increases, and when it becomes excessive
      (and/or the FEV1 falls below 20% to 25%), the PaCO2 begins to increase.
      Therefore, in any patient with asthma, a decreasing PaO2 and an increasing PaCO2,
      even into the normal range, indicates severe airway obstruction that is leading
      to respiratory muscle fatigue and patient exhaustion.

PMID- 8565402
TI  - Inflammation and asthma.
AB  - There is little doubt that chronic asthma represents a unique inflammatory
      process in which the airway has become the target. Observations that were
      originally made nearly 100 years ago have been borne out through the use of
      animal models and technologically sophisticated techniques that allow
      experimentation on isolated regions of the human bronchial tree. It is also
      apparent that the pathophysiologic processes responsible for the airway changes
      observed in asthma are more complex than those presented in this discussion.
      Neurologic, endocrine, and perhaps even psychologic factors may be involved in
      the genesis or promulgation of the asthmatic response. Experiments of nature,
      such as the LAD, provide valuable insights as to the elements necessary to mount
      an inflammatory response. The recent availability of genetically altered animals
      lacking genes for certain cytokines and growth factors, so-called "knock-out"
      mice, may similarly prove useful in the elucidation of the role of individual
      factors to the overall inflammatory cascade. Further understanding of the
      mechanism of the asthmatic inflammatory response will bring us closer to the
      discovery of new therapies designed to treat the causes of asthma, rather than
      palliate the symptoms.

PMID- 8565403
TI  - What the pulmonologist needs to know about allergy.
AB  - A majority of children and young adults with asthma are allergic to common
      allergens in their environment. Over the last 10 years, it has become
      increasingly clear that chronic exposure to these foreign proteins is an
      important cause of the chronic eosinophilic inflammation of the lungs that
      characterizes patients with asthma. The main allergens relevant to asthma are
      those found indoors, that is, mite, cat, dog, and cockroach. Reducing exposure to
      these common indoor allergens is an important anti-inflammatory treatment for
      asthma; furthermore, the techniques of avoidance are increasingly well defined
      and allergen specific.

PMID- 8565404
TI  - Occupational asthma. Diagnosis, management, and prevention.
AB  - Occupational asthma is the most common work-related respiratory disorder but
      frequently goes undetected, leading to poorer clinical outcomes for asthmatic
      patients. Inhalational exposures to both allergens and irritants in the workplace
      cause asthma. The likelihood of recovery hinges on early recognition and
      avoidance of further exposure. This article outlines the clinical approach to the
      detection, management, and prevention of occupational asthma, emphasizing recent
      advances and practical advice on how to investigate the causes of reactive airway
      disease.

PMID- 8565405
TI  - Asthma in infants and small children.
AB  - The wheezy young child is a particularly challenging patient to treat. This
      article focuses on a diagnostic approach and some of the treatment issues
      peculiar to this age group. Specifically addressed are (1) the problem of
      differentiating asthma from wheezy bronchitis in babies and the clinical
      implications of this; (2) general concepts of treating babies in whom many
      commonly used drugs are not FDA approved; (3) inhalation therapy, especially the
      use of metered-dose inhalers with spacers; (4) the standard asthma drugs and
      their beneficial and adverse effects, with particular reference to inhaled
      steroids; and (5) the nonpharmacologic management of asthma. A brief discussion
      of long-term outcome is also included.

PMID- 8565406
TI  - Childhood asthma. Older children and adolescents.
AB  - Asthma is a very significant health problem in children and adolescents, and it
      is disturbing that this problem is increasing despite recent advances related to
      asthma pathogenesis and treatment. In this age group, treatment of asthma may be
      especially challenging because of the need to deal with schools as well as the
      patient and family, and because of concern for the effects of asthma and asthma
      therapy on physical and psychological development. Successful asthma therapy in
      children and adolescents requires close attention to these issues, as well as
      efforts designed to transfer the responsibility of asthma care from the parent to
      the adolescent in an age-appropriate fashion.

PMID- 8565407
TI  - Exercise-induced airway obstruction.
AB  - Exercise is one of the most common precipitants of acute asthma encountered in
      clinical practice. This article examines the prevalence of this condition. Topics
      discussed include historical review, current concepts of pathogenesis, clinical
      features, late reactions, diagnosis, and therapy.

PMID- 8565408
TI  - Gastroesophageal reflux and sinusitis in asthma.
AB  - The evidence that links gastroesophageal reflux (GER) and sinusitis to asthma
      from a pathophysiologic viewpoint is reviewed. The clinical relationships are
      explored in disease prevalence and studies assessing whether interventions that
      treat either GER or sinusitis improve asthma. An overview of patient evaluation
      and treatment is presented.

PMID- 8565409
TI  - Chronobiology and chronotherapy of asthma.
AB  - There is no doubt that many pathophysiologic conditions change over a 24-hour
      period and thus therapy needs to be directed at these changes. In particular,
      asthma has been one of the better-studied disease processes in regard to
      circadian changes in pathophysiology. As we continue to learn more about
      circadian changes, better approaches to treating the disease with the same
      medications will emerge. It should be remembered that many asthmatics do not
      perceive their degree of bronchoconstriction. This was brought forth in Turner
      Warwick's epidemiologic study in that less than one half of the asthmatic
      individuals who had problems with their asthma every night describe their asthma
      as being severe. The majority stated they either had mild or moderate asthma.
      Therefore, it is important that we use objective criteria such as peak flow
      meters in determining an individual patient's day-to-night changes in lung
      function. Then, any therapeutic intervention can be objectively determined at
      home with both the patient and physician gaining knowledge about the ongoing
      asthmatic process.

PMID- 8565410
TI  - Controversies involving inhaled beta-agonists and inhaled corticosteroids in the
      treatment of asthma.
AB  - Controversy over the use of inhaled beta-agonists has dated almost from their
      introduction as a treatment for asthma. Their effectiveness as bronchodilators is
      not disputed, but there is concern that they may worsen asthma control if used
      regularly and that excessive use may increase the risk of death from asthma. Five
      years after the report from Sears and colleagues suggested that regular use of
      fenoterol worsens asthma control, we do not have definitive corroborative
      evidence that this effect of fenoterol is real or is shared by other members of
      the beta-agonist class. It also remains disputed whether the documented
      association between excessive beta-agonist use and death from asthma is a causal
      or a spurious association. Undisputed is the fact that excessive beta-agonist use
      by asthmatics indicates an increased risk of death from asthma and so indicates a
      need for clinicians to advise anti-inflammatory medications for these patients.
      Happily, although there are legitimate concerns about the possible implications
      of the development of tolerance to the non-bronchodilating effects of beta
      agonists, there is currently little evidence that treatment with conventional
      doses of the beta-agonists currently available in the United States, including
      salmeterol, is harmful to asthmatic patients. The controversies over the use of
      inhaled corticosteroids revolve around the issue of whether the clinical benefit
      easily demonstrated with their short-term use is justified in the face of their
      possible long-term systemic toxicity. Unsettled questions about their therapeutic
      use include whether dose dependence can be shown for the clinical benefits of
      inhaled corticosteroids, whether delay in initiating inhaled corticosteroid
      treatment reduces the benefit that can be achieved, and whether the benefits of
      even prolonged therapy are short-lasting. The great unsettled question about
      their toxicity is whether systemic absorption of inhaled corticosteroids
      increases the risk of long-term systemic complications, like osteoporosis,
      cataracts, and growth inhibition. Current evidence suggests that significant risk
      of such toxicity is not likely to be associated with the long-term use of the
      equivalent of 800 micrograms/d of beclomethasone in adults and 400 micrograms/d
      in children. If higher doses are used to obtain greater clinical benefit, the
      answers to these questions may determine the place of new inhaled corticosteroids
      with high local potency and little systemic activity.

PMID- 8565411
TI  - Nonstandard and potential future therapies for asthma.
AB  - This article provides a broad outline of selected areas that offer promise for
      novel therapy in asthma. Special attention is given to pharmacologic approaches
      to asthma and to the kinds of investigation that are required to establish these
      therapies, recognizing that their development may require approaches different
      from those used for the development of drugs designed to symptomatically treat
      asthma.

PMID- 8565412
TI  - Serious interpretive error among three commercial systems for susceptibility
      testing of aztreonam. Aztreonam Study Group.

PMID- 8565413
TI  - Effect of specimen storage, antibiotics, and feminine hygiene products on the
      detection of group B Streptococcus by culture and the STREP B OIA test.
AB  - Agar culture from vaginal swabs is the routine method for diagnosis of maternal
      Group B Streptococcus (GBS) colonization. Swab specimens are often transported to
      a clinical laboratory for processing. In these studies, specimen transport was
      simulated by inoculating swabs with GBS and storing them at selected temperatures
      and with or without transport medium. The recovery of viable GBS was assessed by
      agar culture. GBS antigen was detected immunologically with an Optical
      ImmunoAssay (OIA) method. Swabs that were stored with transport medium harbored
      viable but rapidly declining numbers of GBS. In contrast, a strong OIA signal was
      maintained. Recovery of viable GBS organisms declined more quickly when swabs
      were stored in the absence of transport medium, whereas detection of GBS antigen
      remained consistent. Both methods were tested for interference from either
      antibiotics or feminine hygiene products. These compounds inhibited the detection
      of GBS by culture but had no detrimental effect on the OIA result.

PMID- 8565414
TI  - Beta-D-Glucuronidase activity among prototrophic and auxotrophic variants of
      Escherichia coli and other Enterobacteriaceae commonly implicated in urinary
      tract infections.
AB  - Glucuronidase (GUD) activity of 102 prototrophic, 91 cysteine-requiring, and 19
      thymidine-requiring strains of Escherichia coli was examined using growth from
      MacConkey, CLED, and enriched brain heart infusion (BHI) agars. After 24 h
      incubation, GUD activity was detected in 92%-96% of prototrophic strains and a
      similar proportion of thymidine-requiring strains with most reactions detectable
      in shorter incubation periods. GUD activity among strains requiring cysteine was
      significantly less than that found amongst prototrophic strains. The effects of
      different sources of inocula were evident in the shorter incubation periods.
      Other strains of the Enterobacteriaceae and oxidative strains frequently
      implicated in urinary tract infection were also tested. Here, positive reactions
      were detected among Citrobacter and Enterobacter spp. and a strain of Klebsiella
      oxytoca, but only after 24 h incubation. GUD activity was not detected among the
      oxidative strains tested under the same conditions. Although an incubation time
      of 24 h is necessary to detect activity in a small number of "slow hydrolyzing"
      E. coli, the increased sensitivity thus attained compromises the specificity of
      the test for this organism by simultaneously enhancing detection of the enzyme in
      other enterobacteria.

PMID- 8565415
TI  - Viridans streptococci isolated from the bloodstream. Relevance of species
      identification.
AB  - Over a 4-year-period, 104 isolates belonging to the viridans streptococci were
      recovered from the blood and identified to the species according to Beighton and
      co-workers. Streptococcus oralis was the species most frequently recovered from
      patients in the hematology unit [29 of 39 (74%)]. Streptococcus mitis ranked
      second [seven of 39 (18%)]. Both species were associated with oromucositis.
      Isolates presently identified as S. oralis are mainly those previously identified
      as S. mitis or Streptococcus sanguis II. Streptococcus milleri was most
      frequently isolated in the patients from the general hospital population [28 of
      65 (43%) isolates]: Streptococcus anginosus (n = 20), Streptococcus constellatus
      (n = 4), and Streptococcus intermedius (n = 4). In 14 episodes from the general
      hospital population, clinical significance was judged questionable. From this
      part of the laboratory, clinical significance could not be predicted from the
      number of blood cultures grown, nor from the delay of growth detection. The Rapid
      ID 32 Strep system agreed well with the identifications according to the scheme
      of Beighton et al., whereas the API 20 Strep system did not.

PMID- 8565416
TI  - Evaluation of an enzyme-linked immunoassay for the detection in serum of
      antibodies to Entamoeba histolytica.
AB  - A commercially available enzyme-linked immunoassay (ELISA) was compared to an
      indirect hemagglutination test (IHA) for the detection of antibodies to Entamoeba
      histolytica on 225 patients' serums. All of the 107 serums that had IHA titers of
      < 32 (interpreted as excluding the presence of invasive amebiasis) were ELISA
      negative. Sixty-three of 68 (93%) serums that had IHA titers of > or = 128
      (interpreted as indicative of the presence of active or recent infection) were
      ELISA positive. Fifty serums had IHA titers of 32 or 64 that were considered
      "equivocal," and the ELISA results for these were: six positive, 35 negative, and
      nine "intermediate" (optical density values between the arbitrary positive cutoff
      and the low positive control). It was concluded that "intermediate" (and
      negative) ELISA results should be interpreted as excluding the presence of
      invasive amebiasis. Using these criteria, the results obtained with this ELISA
      appear to compare favorably with those of the "gold standard" IHA. Therefore,
      this ELISA provides a reliable alternative to the IHA for the serologic diagnosis
      of amebiasis, which may be advantageous for some laboratories in terms of lower
      cost, shorter test time, and improved efficiency.

PMID- 8565417
TI  - Evaluation of the Etest for susceptibility testing of anaerobic bacteria.
AB  - We compared the susceptibility test results of 220 anaerobes against 14
      antimicrobials using the Etest (AB Biodisk, Solna, Sweden) with those using the
      National Committee for Clinical Laboratory Standards (NCCLS) standard agar
      dilution method (Wadsworth version). The Etest medium was brucella blood (whole)
      agar and the inoculum size was equivalent to a no. 1 McFarland standard. Thirty
      six percent of Etest results were unreadable after 24 h of anaerobic incubation
      compared to only 5% after 48 h. Also, there were more results with categorical
      agreement with the NCCLS method after 48 h (97.9%) than at 24 h (89%) and more
      very major errors (VMEs) at 24 h (22% of resistant organisms) than at 48 h
      (3.2%). VMEs and major errors occurred most frequently with clindamycin,
      ceftriaxone, and trospectomycin (which should not be used with the Etest) and
      involved the Bacteroides fragilis group and/or Clostridium most commonly. The
      Etest is simple to perform and is a generally reliable method that is optimally
      read after 48 h of incubation. It should be an acceptable alternative to the agar
      dilution standard, although results with certain organism-antimicrobial
      combinations should be read very conservatively because of the frequency of VMEs.

PMID- 8565418
TI  - Comparison of susceptibility to extended-spectrum beta-lactam antibiotics and
      ciprofloxacin among gram-negative bacilli isolated from intensive care units.
AB  - The in vitro activities of extended-spectrum beta-lactam antibiotics (including
      piperacillin, cefotaxime, ceftriaxone, ceftazidime, cefepime, imipenem, and
      meropenems) were assessed and compared with the activity of ciprofloxacin against
      366 clinical Gram-negative bacilli isolates from the intensive care units of
      Taichung Veterans General Hospital. The most prevalent species isolated were
      Pseudomonas aeruginosa and Acinetobacter baumannii. The activities of
      ceftazidime, cefepime, imipenem, and meropenem against these isolates were
      comparable to that of ciprofloxacin. Meropenem was found to be the most potent
      extended-spectrum beta-lactam antibiotic tested and the MIC50s and MIC90s for
      most of these multiresistant strains were lower than those of imipenem,
      ceftazidime, and cefepime, except for Stenotrophomonas maltophilia. The extended
      spectrum beta-lactam antibiotics that were still active against S. maltophilia
      were piperacillin and ceftazidime. More than 50% of Enterobacter spp. were
      resistant to third-generation cephalosporins and piperacillin, but they remained
      susceptible to carbapenems and cefepime.

PMID- 8565419
TI  - Rahnella aquatilis bacteremia in an HIV-infected intravenous drug abuser.
AB  - Rahnella aquatilis, an unusual enteric Gram-negative rod, was isolated from three
      of four blood cultures of an HIV-infected intravenous drug abuser. The outcome
      was favorable after a 14-day course with ciprofloxacin. The identification of R.
      aquatilis isolates is discussed and a synopsis of the previously published
      antimicrobial susceptibility patterns of this microorganism is given.

PMID- 8565420
TI  - Performance of the Gen-Probe amplified Mycobacterium tuberculosis direct test in
      a laboratory that infrequently isolates Mycobacterium tuberculosis.
AB  - The performance of the Gen-Probe Mycobacterium tuberculosis direct (MTD) test was
      assessed in a laboratory whose specimens were derived from a population with a
      low prevalence (1.3%) of tuberculosis. A total of 339 specimens from 113 patients
      were included in the study. Nine of 10 MTD positive samples were culture positive
      (smear positive, n = 7; smear negative, n = 1; smear not ordered, n = 2). The
      10th MTD-positive sample, which was smear and culture negative, was from a
      patient whose two other study specimens were smear and culture positive and who
      had a clinical history consistent with tuberculosis. Prior to and following
      resolution of discrepant results, the sensitivities and specificities of the MTD
      test relative to culture were 100 and 99.7% and 100 and 100%, respectively.

PMID- 8565421
TI  - Comparative in vitro activity of furopenem against aerobic bacteria isolated from
      pediatric patients.
AB  - The in vitro activity of the oral penem furopenem (WY-49605, 545555, SUN5555, and
      ALP201) was tested against clinical bacteria isolated from pediatric patients.
      Furopenem was compared with clarithromycin, cefpodoxime, amoxicillin, amoxicillin
      clavulanate, cefaclor, cefixime, and cefuroxime. Furopenem demonstrated
      consistent activity against Escherichia coli [minimum inhibitory concentration
      (MIC90) = 1.0 microgram/ml)] Klebsiella pneumoniae (MIC90 = 2.0 micrograms/ml),
      Salmonella enteriditis and Shigella spp. (MIC90 = 1.0 microgram/ml), and beta
      lactamase-positive or -negative Haemophilus influenzae (MIC90 = 1.0 microgram/ml)
      and Moraella catarrhalis (MIC90 = 1.0 microgram/ml). Furopenem was also active
      against a number of the Gram-positive organisms tested including methicillin
      susceptible Staphylococcus aureus and penicillin-susceptible Streptococcus
      pneumoniae. These results suggest a potential application for this agent in the
      treatment of children as outpatients.

PMID- 8565422
TI  - Glucocorticoid-remediable aldosteronism.
AB  - Although GRA is said to be one of the least common of the mineralocorticoid
      excess states, it is probably underdiagnosed. Moreover, recent advances in our
      understanding of its pathogenesis has greatly broadened the understanding of this
      disorder. The development of direct genetic testing for GRA has simplified the
      diagnostic approach to GRA and will likely increase the detection of many
      previously undiagnosed cases. Since appropriate treatment can often result in
      normalization of this refractory form of hypertension, a high index of suspicion
      should be maintained for this diagnosis when a patient is diagnosed with
      mineralocorticoid-induced hypertension. It is only through early detection and
      institution of directed treatment that the morbidity and mortality associated
      with GRA can be reduced.

PMID- 8565423
TI  - Physical activity in the treatment and prevention of diabetes.
AB  - The current available epidemiologic evidence supports a substantial benefit from
      maintaining a physically active, as compared to a sedentary life-style. Clinician
      counseling and prescription of regular physical activity should represent a major
      goal in the treatment and primary prevention of diabetes. This responsibility is
      of paramount importance, particularly in light of the high prevalence of physical
      inactivity (based on national survey data, 56% of men and 61% of women in the
      United States either never or irregularly engage in physical activity), and the
      high incidence of diabetes and its complications, including severe
      atherosclerotic disease, in the United States and throughout the world.

PMID- 8565424
TI  - Office management of osteoporosis: a guide for the primary care provider.
AB  - Osteoporosis is greatly increasing in prevalence as the population ages.
      Postmenopausal women are at particularly high risk. I have reviewed the risk
      factors for osteoporosis, the office evaluation, laboratory and radiologic
      testing, and available treatment of osteoporosis. Adequate calcium and vitamin D
      intake is important in prevention and treatment. Estrogen replacement is the
      treatment of choice for the menopausal women who has or is at risk for
      osteoporosis, but several alternatives are available. These drugs prevent bone
      loss but cannot restore lost bone to any significant degree. Until effective
      means of restoring normal bone are discovered, increasing peak bone mass in
      adolescents and young women with the hope of preventing osteoporosis may be the
      most important intervention.

PMID- 8565425
TI  - Evaluation of amenorrhea.
AB  - This article has focused on the evaluation of amenorrhea. Primary amenorrhea
      shares some diagnostic considerations with secondary amenorrhea. Having excluded
      these diagnostic considerations (pregnancy), the patient with primary amenorrhea
      should be further evaluated in consultation with an endocrinologist. Secondary
      amenorrhea is a common clinical complaint and an algorithm is proposed to guide
      the physician through the diagnostic evaluation. The evaluation is centered
      around excluding significant pathology in the central nervous system and
      evaluating for the common gynecological disorder of chronic anovulation. The
      clinical disorders of PCOS and hyperprolactinemia were discussed briefly, and the
      interested reader may obtain further information from the authors referenced in
      this article.

PMID- 8565426
TI  - Drugs to treat the tissue complications of diabetes: peripheral neuropathy.

PMID- 8565428
TI  - Unexplained improvement in diabetes control: a wolf in sheep's clothing.

PMID- 8565427
TI  - Induction of ovulation.

PMID- 8565429
TI  - Compound W: a potential marker in maternal serum for assessing fetal thyroid
      function.

PMID- 8565430
TI  - Diabetes and hypertension.
AB  - Diabetes and hypertension have a higher than expected comorbidity. They share
      common etiology, pathophysiology, and organ effects. Long-term therapeutic goals
      are to prevent renal failure and atherosclerosis. Management should inhibit
      pathophysiologic mechanisms and avoid stimulating them. The most appropriate
      pharmacologic agents to treat hypertension in the diabetic are ACE inhibitors,
      selected calcium channel blockers, alpha adrenengic blockers, and certain central
      alpha agonists. The only diuretics that should be used are indapamide and
      torsemide.

PMID- 8565431
TI  - Management of hyperlipidemia in diabetes.

PMID- 8565432
TI  - How short is too short?
AB  - A review of growth parameters should be a routine part of pediatric care.
      Children and parents need to be helped in understanding normal growth and
      development. Variations in growth should be explained, and concerns of parents
      and children openly discussed. Age appropriate educational materials are often
      helpful. Children with abnormal growth should be referred promptly for definitive
      diagnosis, selection of treatable candidates, and monitoring.

PMID- 8565433
TI  - Update in the treatment of epilepsy.

PMID- 8565434
TI  - Alzheimer's disease: an update.

PMID- 8565435
TI  - Pseudoseizures: an update.

PMID- 8565436
TI  - The management of migraine and cluster headaches.

PMID- 8565437
TI  - Neurodevelopmental variation in school-aged children.

PMID- 8565439
TI  - Office management of common neurologic problems.

PMID- 8565438
TI  - Neuropsychiatry of obsessive-compulsive disorder in children and adolescents.
AB  - Physicians understanding of the pathobiobiology, diagnosis, and treatment of OCD
      in children and adolescents closely resembles that for OCD in adults. Moreover,
      it is now clear that OCD is a neurobehavioral disorder involving dysregulation in
      links between cortical and subcortical circuitry that is substantially influenced
      by serotonergic neurotransmission. Although current treatments are not generally
      curative, given a correct diagnosis and the skillful combination of
      pharmacotherapy with a serotonin reuptake inhibitor and focused cognitive
      behavioral psychotherapy, most children can be helped to resume a normal
      developmental trajectory.

PMID- 8565440
TI  - Syndromes of language dissolution in aging and dementia.
AB  - This article has reviewed the language deterioration of aging, dementia, and the
      syndrome of primary progressive aphasia. Language deterioration is generally mild
      in normal aging but is a universal accompaniment of dementing diseases. Isolated,
      progressive language disturbance, especially nonfluent aphasia, is the hallmark
      of the syndrome called ?Primary Progressive Aphasia? or PPA. The language
      findings in these patients illustrate that distinctions between focal and
      generalized brain disease are difficult. Much remains to be learned about the
      spectrum of diseases that can produce progressive aphasia. The discovery of
      biological or genetic markers for these diseases is likely to lead to a better
      understanding of their behavioral characteristics.

PMID- 8565441
TI  - The neuropsychiatric complications of corticosteroid therapy.
AB  - A variety of neuropsychiatric complications can result from the treatment with
      corticosteroids. Toxic effects that are usually observed result from continued
      use of large dosages or withdrawal of therapy. In some circumstances, low dosages
      of corticosteroids can produce neuropsychiatric dysfunction. Awareness of the
      side effects of corticosteroids should help the physician in the management of
      patients receiving steroid therapy. Knowledge and recognition of the adverse
      neuropsychiatric effects of steroids should enable the physician to promptly
      intervene when adverse reactions develop.

PMID- 8565442
TI  - Failure of the autonomic nervous system.

PMID- 8565443
TI  - The biopsychosocial paradigm and the future of psychiatry.
AB  - Although hazardous, prediction is necessary for sensible programming for the
      future of psychiatry. Because of the multitude of variables essential for
      comprehending normal and abnormal behavior, a complex, all-encompassing model
      takes on increasing importance. Dualism and reductionism have had a chilling
      effect on progress in developing psychiatric models. The biopsychosocial model as
      elaborated by Dr. George Engel would appear to be a major step in moving toward
      an adequate workable model. Dr. Engel rejects the biomedical or Newtonian model
      in favor of the biopsychosocial model, basing his conception in part on
      developments in the past century, particularly the contributions of Einstein,
      Heisenberg, and Planck. The implications and relevance of these advances,
      including the work of Niels Bohr, are presented. Other ideas such as Chaos Theory
      and the work of Roger Penrose are also discussed, together with the new thinking
      that arises from them. This work reinforces notions of holism, leading to a more
      humanitarian psychiatry and medicine.

PMID- 8565444
TI  - The attribution of somatic symptoms in psychiatric outpatients.
AB  - The attribution of common somatic symptoms was investigated in 100 psychiatric
      outpatients. Subjects who were more depressed and alexithymic as measured by the
      Toronto Alexithymia Scale (TAS) tended to endorse a psychological attribution for
      somatic complaints. Somatosensory amplification, anxiety, and inability to
      express and report specific feelings predicted psychological attribution. The
      data support the role of alexithymia in somatization and further explain a
      possible role of psychological attribution of somatic symptoms in the
      underrecognition of physical disorders in psychiatric patients.

PMID- 8565445
TI  - Comorbidity of panic and somatization disorder: a genetic-epidemiological
      approach.
AB  - Although recent diagnostic systems support the distinctiveness of panic disorder
      (PD) and somatization disorder, a high level of comorbidity of these two
      diagnoses has been reported, indicating a need for investigations with external
      validators. One hundred fifty-nine outpatients with DSM-III-R PD and 76 surgical
      controls were screened for lifetime presence of DSM-III-R somatization disorder,
      and the risks for some types of psychiatric disorders in their families were
      computed. In our sample, 23% of women and 5% of men with PD also had DSM-III-R
      somatization disorder did not differ from women with PD only in age at onset of
      panic, agoraphobia, childhood history of separation anxiety, or lifetime
      diagnoses of other disorders. Familial risks for PD, PD-agoraphobia, and alcohol
      dependence were significantly higher for families of women with PD and women with
      PD plus somatization disorder than for controls. The familial risks for
      antisocial personality (ASP) disorder (a familial indicator for the somatization
      disorder spectrum of liability, phenomenologically independent from both PD and
      somatization disorder) were significantly higher for families of women with PD
      plus somatization disorder than for families of women with PD only or for
      controls. Application of DSM-IV criteria for somatization disorder substantially
      decreased the comorbidity with PD. Our data suggest that somatization disorder is
      not simply a form of PD, and that the two disorders may coexist in the same
      subject without sharing a common genetic diathesis. Compared with DSM-III-R, DSM
      IV criteria for somatization disorder appear to be simpler in structure and of
      less complicated application.

PMID- 8565446
TI  - The reliability of distinguishing primary versus secondary negative symptoms.
AB  - The objective appearance of negative symptoms in schizophrenia and other
      psychotic disorders may be a direct reflection of a primary neural abnormality or
      may be secondary to a variety of factors such as neuroleptic side effects,
      depression, positive symptoms, or environmental understimulation. Although there
      is a consensus that it is important to be able to disentangle "primary" versus
      "secondary" negative symptoms, optimal strategies for doing so remain unclear.
      Concerns have been raised about making this distinction based on clinical
      judgment because of potential low reliability in the absence of extensive
      training and/or highly specialized rating scales. This is particularly important
      in terms of the application of DSM-IV criteria for schizophrenia, in which
      negative symptoms play a prominent role. In the context of the DSM-IV
      schizophrenia field trial project, we examined the reliability of making the
      primary versus secondary distinction in a multicenter sample of 462 subjects with
      nonorganic psychotic disorders. Each subject was assessed by two raters, half in
      an interrater design (i.e., conjoint interviews) and half in a test-retest design
      (i.e., independent interviews by two raters conducted 1 day apart). All raters
      used the same semistructured interview instrument, which included an abbreviated
      version of the Scale for the Assessment of Negative Symptoms (SANS). In addition
      to the usual SANS ratings, raters were asked to indicate their judgment as to
      whether the symptom was primary, secondary, or unknown (inadequate information to
      assess). No formal training was provided. Reliability, as quantified by kapp,
      indicated only a fair degree of agreement ranging from 0.48 to 0.68 for
      interrater reliability (median, 0.50) and 0.34 to 0.66 for test-retest
      reliability (median, 0.38). Negative symptoms were rated as primary approximately
      twice as often as secondary, and raters believed they had adequate information to
      make this distinction based only on cross-sectional evaluation in all but 10% of
      the cases. These data suggest that the primary versus secondary distinction
      should not be incorporated into the application of operationalized diagnostic
      criteria. Implications are discussed in terms of balancing reliability and
      validity in the assessment of negative symptoms.

PMID- 8565447
TI  - Bizarre delusions and first-rank symptoms in a first-admission sample: a
      preliminary analysis of prevalence and correlates.
AB  - This report examines the prevalence and correlates of bizarre delusions and
      Schneider's first-rank symptoms (FRS) in a first-admission sample with psychosis.
      A total of 196 patients were assessed with the Structured Clinical interview for
      DSM-III-R (SCID) and given a consensus diagnosis. Project psychiatrists blind to
      the consensus diagnoses coded each delusion and hallucination in the sample for
      both FRS and DSM-III-R bizarreness. Interrater reliability of bizarreness was
      lower than that of FRS (kappa = .681 v 861). The majority of symptoms (72%) were
      neither bizarre nor FRS, and of the remainder, bizarre delusions that were not
      also FRS were extremely uncommon. The prevalence of FRS was 70% in schizophrenia,
      29% in psychotic bipolar disorder, and 18% in psychotic depression. For seven
      schizophrenic patients (7.45%), diagnosis of that disorder depended on the
      presence of a DSM-III-R bizarre delusion to meet criteria. There was a trend for
      FRS to be associated with poorer prognostic features in the schizophrenic sample.
      We concluded that although the constructs of bizarre delusions and FRS overlap,
      FRS were a more important feature in schizophrenia than bizarreness. The rarity
      of bizarre delusions that were not FRS, combined with the lower reliability of
      their assessment as compared with that of FRS, raises questions about the
      continued emphasis on this phenomenon in the definition of schizophrenia.

PMID- 8565448
TI  - Gender effects on the clinical presentation of alcoholics at a psychiatric
      hospital.
AB  - Despite the clinical importance of gender effects on symptom patterns and
      comorbidity patterns in alcoholics, little is known about such effects in
      treatment facilities other than alcoholism treatment centers. This study
      evaluated the effect of gender on the clinical profile of 604 alcoholics who
      presented for initial evaluation and treatment at a psychiatric hospital. It
      demonstrated that major depression and accompanying depressive and anxiety
      related symptoms are more prominent in female alcoholics than in male alcoholics,
      whereas antisocial personality disorder and antisocial symptoms are more
      prominent in male alcoholics presenting to a psychiatric hospital. The study also
      demonstrated that reversed neurovegetative symptoms are more severe in female
      than in male alcoholics.

PMID- 8565450
TI  - The Talbieh Brief Distress Inventory: a brief instrument to measure psychological
      distress among immigrants.
AB  - The purpose of this study was to develop and test the Talbieh Brief Distress
      Inventory (TBDI), a 24-item self-report questionnaire that measures psychological
      distress among immigrants. The TBDI combines items from the Brief Symptom
      Inventory (BSI) and the Psychiatric Epidemiology Research Interview
      Demoralization Scale (PERI-D). It includes a global score and six scales
      (obsessiveness, hostility, sensitiveness, depression, anxiety, and paranoid
      ideation). A convenience sample of 966 recent immigrants to Israel from the
      former Soviet Union were asked to complete a Russian-language version of the BSI
      and PERI-D as part of a study on immigrants' psychological adjustment. The TBDI
      is a combination of 13 items from the BSI and 11 items from the PERI-D. Items for
      inclusion were based on results of a separate factor analysis for the BSI and
      PERI-D and removal of repetitive items. We compared the total score with the
      total PERI-D and BSI and developed gender-specific cutoff points of caseness for
      the TBDI by comparison to known PERI-D and BSI cutoff points. We also checked for
      reliability using Cronbach's alpha. The TBDI correlated highly with the PERI-D (r
      = .93) and with the BSI (r = .82). Reliability of the scales and the overall
      instrument ranged from Cronbach's alpha of .60 to .89. TBDI caseness cutoff
      points were in close agreement with the BSI and PERI-D as reflected by kappa
      scores that ranged from .66 to .79. The TBDI is a promising instrument for
      screening populations for psychological distress and symptomatology. It is
      available in English, Hebrew, and Russian.

PMID- 8565449
TI  - Concurrent cocaine withdrawal is associated with reduced severity of alcohol
      withdrawal.
AB  - The purpose of this study was to implement an empirical assessment of the
      clinical response to standard alcohol detoxification during withdrawal from both
      alcohol and cocaine. One hundred forty-nine males consecutively admitted in acute
      alcohol withdrawal to a hospital-based detoxification unit were studied. All
      subjects completed a 4-day chlordiazepoxide detoxification. Patients who used
      drugs other than cocaine were excluded. Fifty-five subjects withdrawing only from
      alcohol and 94 subjects withdrawing from both alcohol and cocaine, as evidenced
      by positive urinalysis and history, were studied. Both groups reported similar
      amounts of daily alcohol intake and had a similar age of onset of alcohol
      dependence. Parental alcoholism was equally frequent in both groups.
      Statistically, several variables were directly related to severity of alcohol
      withdrawal, including associated cocaine abuse, age, abnormal laboratory values,
      and duration of homelessness. As measured by the Alcohol Withdrawal Scale (AWS),
      alcohol withdrawal was less severe among cocaine users, not only at intake but
      throughout the 4-day detoxification. Singly addicted alcoholics were older and
      had longer drinking histories, more prior detoxifications, and more abnormal
      laboratory values than cocaine users. A multiple regression analysis demonstrated
      a significant relationship between cocaine and severity of alcohol withdrawal.
      Cocaine users more frequently requested reductions in chlordiazepoxide dosages
      than singly addicted alcoholics, complaining of dysphoria, sedation, and
      weakness. The severity of alcohol withdrawal was associated with recent cocaine
      use, age, laboratory abnormalities, and duration of homelessness. Concurrent
      cocaine withdrawal in the sample was associated with reduced severity of alcohol
      withdrawal. Possible neurobiological mechanisms, as well as study limitations
      affecting interpretation of the findings, are discussed. Tailored detoxification
      as opposed to standard detoxification regimens may be more appropriate for the
      clinical management of combined alcohol-cocaine withdrawal.

PMID- 8565451
TI  - Clinical relevance of adjustment disorder in DSM-III-4 and DSM-IV.
AB  - This study examines the diagnosis of adjustment disorder in DSM-III-R. In view of
      the methodological problems associated with this, we investigated clinical
      characteristics of patients to whom the diagnosis had been applied. The patients
      in question were treated at the University Psychiatric Outpatient Clinic in
      Lausanne, Switzerland (N = 1,308). Four groups of comparisons are made: between
      adjustment disorder, other diagnoses, and no diagnosis; between adjustment
      disorder with depressed mood and other mood disorders; between adjustment
      disorder with anxious mood and anxiety disorders; and between the clinical
      subdivisions of adjustment disorder. This diagnosis is characterized by a high
      number of marital stressors, low age, predominance of women, and short period of
      treatment. The clinical profile is marked by a predominance of depressive and
      mixed types, and the relationship between these is demonstrated. Finally, the
      course of a certain proportion of these disorders goes beyond the 6-month period
      stipulated by DSM-III-R. This result justifies the modifications introduced in
      DSM-IV.

PMID- 8565452
TI  - The European standard series. European Environmental and Contact Dermatitis
      Research Group (EECDRG).
AB  - Changes to the European standard series which have taken place since the last
      officially recommended alterations in 1988, are explained. New to the series is
      the sesquiterpene lactone mix. The PPD black rubber mix and the quinoline mix
      have been replaced by single components; one of the p-hydroxybenzoates has been
      left out of the paraben mix. Ethylenediamine dihydrochloride has been dropped
      from the series.

PMID- 8565453
TI  - Screening for corticosteroid contact hypersensitivity.
AB  - To evaluate which corticosteroids are most useful for the detection of
      corticosteroid contact allergy in our population, 2123 patients were patch tested
      with a series of 6 corticosteroids, in parallel with a standard series, and other
      relevant investigations. 127 patients (5.98%) were allergic to one or more
      corticosteroids; 96 to tixocortol pivalate, 51 to hydrocortisone butyrate, 47 to
      budesonide, 11 to betamethasone valerate, 11 to clobetasone butyrate and 8 to
      clobetasol propionate. 511 patients with negative patch tests to the limited
      corticosteroid series were in addition tested to a further 12 corticosteroids;
      only 1 of these patients reacted to a corticosteroid. A combination of tixocortol
      pivalate and budesonide thus detected 91.3% of corticosteroid-allergic subjects.
      We believe that both these allergens should be included in the standard series
      and that there may be a case for extending this further.

PMID- 8565454
TI  - Pretreatment of the test area with 1-day occlusion improves the response rate to
      NiSO4 5% pet. patch tests in subjects with a positive history of nickel allergy.
AB  - A group of 58 women, aged 18 to 51 years, with a clinical history of nickel
      allergy, who exhibited equivocal or negative reactions to nickel sulfate 5% pet.
      patch tests performed on the skin of the back, were recruited consecutively from
      the patch test clinic from September 1993 to June 1994. In order to improve the
      response rate to NiSO4 5% pet. patch tests, a testing procedure utilizing
      pretreatment of the test area by 1-day (24-h) occlusion was introduced. Patients
      underwent 2 patch tests on adjacent sites of the volar surface of both forearms.
      3 of the patch tests were performed with 40 mg nickel sulfate 5% pet., whereas a
      control test was carried out by occluding with an empty chamber. 2 of the nickel
      sulfate test sites were pretreated with 1-day occlusion performed with an empty
      chamber. A visual grading system and echographic measurement were used to
      quantify the responses 30-40 min after patch test removal. Echographic
      evaluations were carried out using a 20 MHz B-scanner. Measurement of skin
      thickness and determination of the hypoechogenic dermal area, both considered to
      be parameters of inflammation, were used to evaluate the intensity of the
      allergic reaction. At the 3-day (72-h) evaluation, 19 subjects out of 58 clearly
      showed positive reactions to nickel sulfate 5% pet. at pre-occluded skin sites.
      Moreover, values of skin thickness and of 0-30 areas at positive pre-occluded
      nickel test areas were higher in respect to control test areas, confirming
      clinical evidence of increased response to NiSO4 after occlusion.

PMID- 8565456
TI  - Streptozotocin: inherent but not expressed skin sensitizing activity.
AB  - We have shown previously that the alkylating agent streptozotocin (STZ) fails to
      induce responses in the murine local lymph node assay, a predictive test for
      contact sensitizing potential. In the present study, we demonstrate that this
      same compound when injected intradermally into the ears of mice provokes a dose
      dependent induction of draining lymph node cell proliferation. These data
      indicate that the intrinsic immunogenicity of STZ is not displayed in the local
      lymph node assay under conditions of conventional topical exposure, secondary to
      a failure to cross the lipophilic stratum corneum in sufficient quantities. This
      finding has implications for the discernment of structure-activity relationships
      in contact sensitization.

PMID- 8565455
TI  - The allergens of nail polish. (I). Allergenic constituents of common nail polish
      and toluenesulfonamide-formaldehyde resin (TS-F-R).
AB  - Nail polish that has completely dried on the fingernails contains water-soluble
      components that attain the skin during extensive but transient contact. This was
      proven by water extraction of thin layers of nail polish that had been painted
      onto glass plates and allowed to dry for 3 days. Comparing the isolated fractions
      and compounds with known nail polish ingredients revealed that the water-soluble
      substances are para- and ortho-toluenesulfonamide, dibutyl phthalate and 3
      constituents of toluenesulfonamide-formaldehyde resin (TS-F-R), which is the
      basic material of almost all nail polishes sold worldwide. 12 female patients
      with proven nail polish allergy were patch tested with 21 nail polish components,
      including those isolated. Only 2 fractions were positive. These contained a
      monomer and a dimer created during condensation of TS-F-R. Their structures were
      elucidated. The 3rd compound, a trimer, remained negative, except in 1 case.

PMID- 8565457
TI  - Contact dermatitis caused by cetrimide in antiseptics.
AB  - Cetrimide and chlorhexidine are widely used antiseptics. Irritant contact
      dermatitis from cetrimide has been reported, but only rarely and without
      pathologic study. We report the clinical and pathologic findings from a series of
      18 cases of contact dermatitis caused by antiseptic solutions containing 3%
      cetrimide and 0.3% chlorhexidine. The patients consisted of 10 males and 8
      females, aged from 2 to 62 years. Most patients developed pruritic, burning or
      painful rashes over the flexors and genitalia after 1 to 4 weeks of daily use of
      undiluted antiseptics for an underlying pruritic dermatosis. The lesions varied
      from slight scaling with minimal erythema to fiery or dusky red patches with a
      glazed surface. The rashes resolved in 2 to 4 weeks after discontinuing the
      antiseptics. Concentric annular lesions were noted in some patients. Patch
      testing revealed negative reaction to chlorhexidine 0.5% aq. but irritant
      reaction to cetrimide 0.5, 1 or 2% aq. and Savlon at 1:3 or 1:6 dilution. Light
      microscopy showed compact orthokeratosis and confluent parakeratosis without
      spongiosis. Our study suggests that the dermatitis was an irritant reaction to
      cetrimide after improper self-application of the antiseptic liquids for
      underlying pruritic rashes or personal hygiene. Recognition of the characteristic
      xerosis- or chemical-burn-like features primarily involving the flexors or
      genital area is essential to the diagnosis.

PMID- 8565458
TI  - Occupational hand dermatitis in hospital environments.
AB  - Health care personnel form the 5th category at major occupational risk of skin
      disease in Italy. The aim of this study was to assess the prevalence and clinical
      relevance of contact dermatitis in a group of 1301 employees of the Perugia
      Monteluce Hospital (658 females and 643 males; mean age 39.8 years) who answered
      a self-administered questionnaire elaborated by the authors. The subjects with
      anamnestic hand dermatitis and/or atopic mucosal reactions were clinically
      examined and submitted to skin tests (patch and/or prick tests). Contact
      dermatitis of the hands and/or forearms occurred in 21.2% and was significantly
      more frequent (p < 0.001) in women, subjects under 31 years of age, workers in
      internistic and surgical fields, cleaners and nurses. In the majority of cases
      (94.9%), the lesions were irritant in origin and mainly related to disinfectants
      (especially, chlorhexidine gluconate and glutaraldehyde) and gloves (latex
      proteins and starch glove powder, rather than accelerators and additives of
      rubber). Finally, atopy seemed to favour the onset of hand dermatitis. The
      importance of these results for preventive measures of contact dermatitis in
      hospital employees is discussed.

PMID- 8565459
TI  - Immediate irritant reactions to benzoic acid are enhanced in washed skin areas.
AB  - Factors affecting immediate irritant skin reactions are poorly understood. Our
      purpose was to study the effect of washing on reactions to benzoic acid, a well
      known immediate-type irritant. 12 test subjects washed their left upper arms with
      a diluted dishwashing liquid 2X daily for 6 days. Benzoic acid in a dilution
      series was tested on both upper arms on days 0, 3 and 6. The reactions were
      graded visually, and the blood flow, skin color, transepidermal water loss and
      electrical capacitance of the test sites were measured. On days 3 and 6, the
      benzoic acid reactions were stronger on the washed arm than on the control arm.
      This was clinically visible and was associated with changes in blood flow and
      skin color measurements. Washing itself did not usually cause visible erythema,
      but transepidermal water loss increased and electrical capacitance decreased. Low
      concentrations of irritant substances, such as benzoic acid, may cause clinically
      relevant reactions in repeatedly washed skin. This should be taken into
      consideration in assessing product safety in the cosmetic, medical and household
      chemical industries, and when tests for chemical skin irritancy are designed and
      the results of such tests interpreted.

PMID- 8565460
TI  - The effects of protective occlusive gloves on stratum corneum barrier properties.
AB  - Data suggests that protection from gloves is paradoxically reduced because of
      effects of occlusion on the skin. The aim of this study was to characterize these
      effects on physical and functional properties of stratum corneum. Volunteer
      trials were conducted using patches of polyvinyl chloride (PVC) glove material on
      the skin. Impairment of barrier function was assessed by measuring transepidermal
      water loss (TEWL). Hydration and water sorption-desorption was assessed using
      skin conductance. The major finding was a short-term impairment of barrier
      function, measured as an increase in TEWL of 1.7 gn-2h-1 (95% C.I. 0.4 to 2.6 gn
      2h-1,p < 0.01). Temporary increases in hydration and water sorption were also
      observed. On this basis, the effects of wearing PVC gloves over 2 days on stratum
      corneum barrier properties on the dorsum of the hand were studied. TEWL
      measurements remained elevated by 1.5 gn-2h-1 the day after occlusive glove
      removal (95% C.I. 0.2 to 2.8 gn-2h-1, p < 0.01), indicating a possible cumulative
      effect. In conclusion, our studies demonstrate a potential hazard resulting from
      the repeated use of protective gloves.

PMID- 8565461
TI  - Isolation and quantification of a new tuliposide (tuliposide D) by HPLC in
      Alstroemeria.
AB  - From aqueous extracts of flowers, stems and leaves of 1 Brazilian and 15 Chilean
      Alstroemeria species, the content of a new tuliposide, named tuliposide D, was
      determined by isocratic reversed-phase high-performance liquid chromatography (RP
      HPLC), using distilled water:methanol (80:20) as mobile phase. The compound was
      detected by a UV-detector at 208 nm. Tuliposide D was found in almost all
      Alstroemeria species investigated, although in very different amounts. Most
      species contained relatively small amounts of tuliposide D, especially in the
      leaves. However, A. hookeri ssp. cummingiana, A. presliana ssp. presliana, A.
      pseudospathulata and A. revoluta contained large amounts of tuliposide D in all
      plant parts. Tuliposide D was identified as 1,6-di-(4-hydroxy-2
      methylenebutanoate)-beta-D-glucopyranose by UV, FAB-MS, 1H- and 13C-NMR. The
      content of the allergens 6-tuliposide A and tulipalin A was also determined by RP
      HPLC and the possibility that tuliposide D is a further causative agent of
      allergic contact dermatitis in Alstroemeria is discussed.

PMID- 8565462
TI  - Euxyl K 400: incidence of sensitization, patch test concentration and vehicle.
AB  - The aim of this study was to verify the most suitable vehicle and concentration
      for testing Euxyl K 400 and its individual ingredients, and to evaluate the
      prevalence of sensitization to this preservative over the years in Italy. From
      January 1991 to October 1994, Euxyl K 2.5% pet. was positive in 99 patients (35
      male, 64 female) out of 3455 (2.8%). Of these, 22 out of 855 patients had a
      positive reaction during 1991 (2.6%), 29 out of 1037 in 1992 (2.8%), 28 out of
      858 in 1993 (3.3%), and 20 out of 705 in 1994 (2.8%). 51 of the 99 patients with
      a reaction to Euxyl K 400 2.5% pet. showed a positive reaction to
      dibromodicyanobutane 0.5% pet. and 2 to phenoxyethanol 5% pet. The results of
      patch testing with serial dilutions of Euxyl K 400 in different vehicles indicate
      that water is a good vehicle for testing the preservative. However, since Euxyl K
      400 is only hydrosoluble to a limited extent, the maximum concentration that can
      be tested using water is 0.5%, and so with this concentration about 40% of
      sensitized patients are missed. The results of patch testing with serial
      dilutions of Euxyl K 400 in petrolatum demonstrate that concentrations lower than
      2.5% are not suitable for detection of all sensitized patients. Euxyl K 400 in
      ethanol frequently causes irritant reactions without offering significant
      advantages in detecting sensitized patients.

PMID- 8565463
TI  - Contact allergy to topical corticosteroids: a screening study with a
      corticosteroid mix. Portuguese Contact Dermatitis Research Group (GPEDC).

PMID- 8565464
TI  - Lymphomatoid-like contact dermatitis from cobalt naphthenate.

PMID- 8565465
TI  - Occupational allergic contact dermatitis caused by ylang-ylang oil.

PMID- 8565466
TI  - Allergic contact dermatitis from colistin.

PMID- 8565467
TI  - Contact urticaria from polyurethane-membrane hypoallergenic gloves.

PMID- 8565468
TI  - Sensitization to white petrolatum used as a vehicle for patch testing.

PMID- 8565469
TI  - Usefulness of titanium implants for systemic contact dermatitis due to
      orthopaedic prostheses.

PMID- 8565470
TI  - Methyl acrylate: a new sensitizer in nail lacquer.

PMID- 8565471
TI  - Acute generalized exanthematous pustulosis (AGEP): manifestation of drug allergy
      to propicillin.

PMID- 8565472
TI  - Contact allergy to components of glue in insulin pump infusion sets.

PMID- 8565473
TI  - Coral dermatitis in the aquarium industry.

PMID- 8565474
TI  - Contact sensitivity to Atlas G-1441.

PMID- 8565475
TI  - Contact allergy to neopentyl glycol di-iso-octanoate.

PMID- 8565476
TI  - Delayed hypersensitivity reaction to the preservative myristyl picolinium
      chloride.

PMID- 8565477
TI  - In vivo assessment of irritants made simple and subject-friendly.

PMID- 8565478
TI  - Contact sensitization to dipropylene glycol in an eczema population.

PMID- 8565479
TI  - Severe phototoxic reaction secondary to the application of a fig leaves'
      decoction used as a tanning agent.

PMID- 8565480
TI  - Erythema-multiforme-like contact dermatitis due to phenylbutazone.

PMID- 8565481
TI  - An unusual case of sensitization to methylchloro- and methyl-isothiazolinone
      (MCI/MI).

PMID- 8565482
TI  - Effect of age and sex on the induction and elicitation of allergic contact
      dermatitis.
AB  - This article reviews the effect of age and sex on the induction and elicitation
      of allergic contact dermatitis (ACD). We found that the incidence of ACD in
      childhood is lower than in adults; this may be explained by less exposure to
      allergens, lack of immune response and limited patch test studies in this age
      group. In the elderly, there is an age-dependent decrease in the incidence of
      ACD, with decreased sensitization to new allergens and waning responses in
      previously sensitized subjects. There is extensive controversy about the effect
      of sex differences in ACD. The induction phases of ACD in both sexes are
      different due to differences in exposure to the allergens from occupations,
      habits and cultures. Differences in elicitation phases of ACD in both sexes are
      not confirmed. Women tend to have a higher incidence of ACD and higher
      immunologic response to exposure allergens than men. Thus we can only imprecisely
      define the effect of age and sex on the induction and elicitation of ACD. Further
      prospective studies should be done to answer these questions.

PMID- 8565483
TI  - Two-dimensional blood flow determinations in allergic reactions using laser
      Doppler scanning.
AB  - The new technique of laser Doppler scanning (LDS) provides a 2-dimensional
      pattern of cutaneous microcirculation, which offers a visual image and can
      quantify the intensity and expansion of perfusion. With the help of this
      technique, we examined the microcirculatory pattern of Type IV reactions to
      recall antigens, which were applied using a test stamp (Multitest Merieux). The
      measurements were performed before application of the test stamp as well as 10
      min, 24, 48 and 72 h afterwards. The inflammatory hyperemia was evaluated using
      LDS and unidimensional laser Doppler fluxmetry. The diameter of the inflammatory
      infiltrate was quantified by means of palpation, the thickness by means of high
      resolution 20 MHz sonography. The clinically visible erythema was measured
      planimetrically. An unspecific hyperemia resulting from the trauma of the stamp
      revealed no evident infiltrate under sonography 10 min after the test
      application. Depending of the individual reaction, the mean flux and the
      expansion of the hyperemia were at their peak after 48 h. The flux values were at
      a maximum in the center of the inflammatory reaction and dropped continuously
      toward the periphery. The area of the hyperemia seen in the LDS image was
      significantly larger than the expansion of the erythema measured planimetrically,
      but there was a significant correlation. The perfusion correlated significantly
      with the infiltration diameter (24 h, 48 h, 72 h) and the infiltration thickness
      48 h after testing. All in all, it was possible to measure directly and without
      touching the skin and to quantify a subclinical pattern of skin perfusion as a
      response to and inflammatory reaction on a 2-dimensional display.

PMID- 8565484
TI  - Occupational allergic contact dermatitis and contact urticaria caused by
      polyfunctional aziridine hardener.
AB  - Polyfunctional aziridine (PFA) is increasingly used as a water-based cross-linker
      in 2-component paints, paint primers, lacquers, topcoats and other protective
      coatings. The cross-linker (PFA hardener) is made by reacting multifunctional
      acrylic monomer with a highly reactive aziridine compound. During 1992-1993, we
      came across 2 patients with allergic patch test reactions provoked by PFA
      hardener. One of the patients was a parquet layer, and the other a printer.
      Allergic contact dermatitis (ACD) was diagnosed by positive allergic patch test
      reactions to PFA hardener in a dilution series in pet.:0.3%-1% gave ++ to
      allergic reactions in both patients, whereas 0.1% gave a weak (+) or questionable
      reaction (?+), respectively. The methacrylate patch test series was negative in
      both patients, although gas chromatography/mass spectrometry analysis showed that
      PFA hardener contained 0.3% of trimethylolpropane triacrylate (TMPTA), a
      multifunctional acrylic monomer. One of the patients also had symptoms of contact
      urticaria, and a prick test with PFA hardener (1% aq.) induced a histamine-sized
      prick test reaction. The positive reactions with the PFA hardener and the
      negative reactions with the starting chemicals and additives in PFA, namely
      acrylates, propyleneimine and dimethylethanolamine, indicate that PFA caused ACD.
      This is in accordance with our previous observations, but differs from the
      reports of others, whose patients had been sensitized to acrylates present as
      remnants in the PFA hardener. As test substance, 0.5% PFA hardener in pet. is
      recommended for patch testing. Testing should be performed in patients with
      contact dermatitis if exposure to PFA has occurred. Skin prick tests may be of
      help to detect contact urticaria.

PMID- 8565485
TI  - Is the European standard series suitable for patch testing in Riyadh, Saudi
      Arabia?
AB  - Due to the lack of a regional patch test series in our geographical area, the
      suitability of the European standard series was evaluated by patch testing
      dermatitis patients in Riyadh, Saudi Arabia. Of 240 consecutive patients with
      various forms of dermatitis, 136 (57%) showed 1 or more positive patch tests,
      women, 74 (54%), slightly outnumbering men, 62 (46%). Positive reactions were
      found to 21 of the 22 items in the test series. Sensitization was most common to
      nickel sulfate (51 = 37.5%), potassium dichromate (48 = 35%) and cobalt chloride
      (43 = 32%) The frequency of sensitization to nickel was higher in women (41 =
      30%) while that to dichromate was higher in men (39 = 29%). Less reactions were
      found to fragrance mix (21 = 15%), formaldehyde (15 = 11%) and neomycin sulfate
      (15 = 11%). Sensitization to other allergens ranged between 10 and 1%. Less than
      1% of patients (0.7%) reacted to benzocaine and none to primin. The frequency of
      occurrence of multiple sensitivities is also presented. We conclude that the
      European standard series is suitable for patch testing dermatitis patients in our
      region, with the exception of benzocaine and primin. The addition of 3 allergens
      that could be of local relevance is discussed.

PMID- 8565486
TI  - Skin irritation in man: a comparative bioengineering study using improved
      reflectance spectroscopy.
AB  - Variable types of skin irritation were induced in 8 human female volunteers,
      ranging from subclinical to visible erythema with slight oedema. Skin reactions
      were graded clinically and objectively using transepidermal water loss (TEWL),
      laser Doppler flowmetry (LDF) and improved reflectance spectroscopy. This last
      technique enables separation of in vivo erythemas into relatively deoxygenated
      (venous--deoxy hem) and oxygenated (arterial--oxy hem) haemoglobin components.
      Compared to uninvolved skin, an empty patch increased oxy hem by 197% +/- 121% (p
      < 0.05). Exposure to vehicles also changes skin biophysics. At sodium lauryl
      sulfate (SLS) and hydrochloric acid (HCl) exposed sites, a linear correlation
      between concentration and oxy hem, LDF and TEWL was found. These chemicals
      predominantly increased TEWL values. Nonanoic acid (NON) and imipramine (IMI)
      also raised oxy hem, LDF and TEWL values linearly at increasing concentrations.
      Although IMI 2.5% clinically was graded as a type ++ response, no significant
      increase in TEWL was found. The improved reflectance spectroscopic technique
      proved valid in skin irritation studies, with a higher sensitivity than laser
      Doppler flowmetry, and allowed irritant vascular reactions to be discriminated
      into arterial and venous components. Furthermore, our observations clearly
      demonstrate that clinically indistinguishable skin irritation reactions induce
      significantly different changes in barrier function (disruption) and vascular
      status.

PMID- 8565487
TI  - Oral lichenoid lesions, mercury hypersensitivity and combined hypersensitivity to
      mercury and other metals: histologically-proven reproduction of the reaction by
      patch testing with metal salts.
AB  - We report 11 patients seen between 1991 and 1994 with oral lichenoid lesions
      (OLL). In 10 cases, there was contact with dental amalgam fillings, and in
      patient no. 10 with both amalgam restorations and a gold crown. The last patient
      had, in addition to her OLL, lichen planus of the skin and genital mucosa. In 5
      cases, combined sensitization to mercury and other metal salts, particularly gold
      sodium thiosulfate (GST) and palladium chloride (PDC), was observed. In 10
      patients, the lesions considerably improved or totally cleared within 1 to 9
      months of replacement of restoration materials. Histological examination of
      biopsies from the test sites of amalgam, mercuric chloride, GST and PDC, taken 10
      or 17 days after application of patch tests, showed lichenoid changes in 7
      patients with at least 1 of the allergens. As at least 2 patients had
      inflammatory lesions of the oral mucosa related to both amalgam and gold
      restorations, combined sensitization to inorganic and organic mercury
      derivatives, GST and, in 1 case, PDC, a "dental restoration metal intolerance
      syndrome" is proposed.

PMID- 8565488
TI  - Erythema-multiforme-like eruption due to topical contactants: expression of
      adhesion molecules and their ligands and characterization of the infiltrate.
AB  - Erythema-multiforme-like reactions are a rare manifestation of allergic contact
      sensitivity, the pathomechanisms of which and their possible relationship to
      erythema multiforme remain unclear. We present our histopathological and
      immunohistochemical findings regarding the expression of several adhesion
      molecules and immunophenotypic markers of the infiltrate in skin biopsy specimens
      from 2 cases of erythema-multiforme-like reactions due to contact sensitizers and
      3 cases of typical post-herpetic erythema multiforme. The histopathological
      pattern of erythema-multiforme-like reactions was characterized by an upper
      dermal perivascular lymphoid infiltrate with exocytosis and keratinocyte
      necrosis; in 1 of the cases, there were foci of spongiosis and an admixture of
      eosinophils in the infiltrate. In comparison with biopsy specimens from cases of
      typical erythema multiforme, in both cases of erythema-multiforme-like reactions,
      the epidermal expression of ICAM-1 was more prominent, the % of CD4+ cells in the
      infiltrate was higher and the % of CD69+ cells was lower. There were no other
      significant differences in the cell phenotype of the infiltrate or in adhesion
      molecule expression in biopsy samples from both disorders.

PMID- 8565489
TI  - Patch testing with fragrances: results of a multicenter study of the European
      Environmental and Contact Dermatitis Research Group with 48 frequently used
      constituents of perfumes.
AB  - The objective of this study was to determine the frequency of reactivity to a
      series of commonly used fragrances in dermatological patients. A total of 48
      fragrances (FF) were chosen, based on the publication of Fenn in 1989 in which
      the top 25 constituents of 3 types (1. perfumes, 2. household products, 3. soaps)
      of 400 commercial products on the US market had been determined. In a pilot study
      on a total of 1069 patients in 11 centres, the appropriate test concentration and
      vehicle were examined. For most fragrances, 1% and 5% were chosen, and petrolatum
      proved to be the best vehicle in comparison to isopropyl myristate and diethyl
      phthalate. In the main study, a set of 5 to 10 fragrances at 2 concentrations was
      patch tested in each centre on a minimum of 100 consecutive patients seen in the
      patch test clinic. These patients were also patch tested to a standard series
      with the 8% fragrance mix (FM) and its 8 constituents. In patients with a
      positive reaction to any of the 48 FF, a careful history with regard to past or
      present reactions to perfumed products was taken. A total of 1323 patients were
      tested in 11 centres. The 8% FM was positive in 89 patients (8.3% of 1072
      patients). Allergic reactions to the constituents were most frequent to oak moss
      (24), isoeugenol (20), eugenol (13), cinnamic aldehyde (10) and geraniol (8).
      Reactions read as allergic on day 3/4 were observed only 10X to 7 materials of
      the new series (Iso E Super (2), Lyral (3), Cyclacet (1), DMBCA (1), Vertofix
      (1), citronellol (1) and amyl salicylate (1)). The remaining 41 fragrances were
      negative. 28 irritant or doubtful reactions on day 3/4 were observed to a total
      of 19 FF materials (more than 1 reaction: 5% citronellol (2), 1% amyl salicylate
      (2), 1% isononyl acetate (3), 0.1% musk xylol (2), 1% citral (2), and 1% ionone
      beta (2)). Clinical relevance of positive reactions to any of the FF series was
      not proved in a single case. This included the 4 reactions in patients who were
      negative to the 8% FM. In conclusion, the top 25 fragrances commonly found in
      various products caused few reactions in dermatological patients and these few
      appeared to be clinically irrelevant, with the possible exception of Lyral.
      However, this data should be interpreted in the light of the relatively small
      number of patients tested (only 100 in most centres).

PMID- 8565490
TI  - Immediate and delayed contact hypersensitivity to verbena plants.
AB  - Plants from the Verbenaceae family may cause contact dermatitis of unknown
      nature. This report describes 2 cases of allergic reactions to the Verbena
      species. A teenage boy developed an anaphylactic allergic response following
      contact with the leaves of Verbena hybrida. Characterization of the patient's
      specific IgE response to Verbena hybrida, using Western blots and
      autoradiography, identified the specific 62000 Dalton allergen present in the
      verbena leaves to which the patient reacted. This is the first report of an IgE
      mediated immediate contact hypersensitivity reaction to Verbena hybrida, a common
      perennial in South African gardens. The other case was a 23-year-old female
      gardener who developed immediate and delayed-type contact dermatitis from Verbena
      elegans 'Cleopatra' produced in a Danish nursery. Prick tests to plant material
      were considered positive and of an allergic nature.

PMID- 8565491
TI  - Patch test results in hairdressers with contact dermatitis in Greece (1985-1994).

PMID- 8565492
TI  - Warts in aquarium industry workers.

PMID- 8565493
TI  - Allergic contact dermatitis from cyclopiroxolamine?

PMID- 8565494
TI  - Effectiveness of disperse dyes mix in detection of contact allergy to textile
      dyes: an Italian multicentre study.

PMID- 8565495
TI  - Contact sensitivity to vanilla in a lip salve.

PMID- 8565496
TI  - Fixed drug eruption due to citiolone.

PMID- 8565497
TI  - Contact urticaria from formaldehyde in a root-canal dental paste.

PMID- 8565498
TI  - Erythema-multiforme-like contact dermatitis due to capsicum.

PMID- 8565499
TI  - Allergic contact dermatitis in an aroma therapist with multiple sensitizations to
      essential oils.

PMID- 8565500
TI  - Allergic contact dermatitis from epoxy resin in Singapore.

PMID- 8565501
TI  - Cross-reactive type IV hypersensitivity reactions to benzodiazepines revealed by
      patch testing.

PMID- 8565502
TI  - Toxicodendron succedaneum (Rhus tree), New Zealand's poison ivy.

PMID- 8565503
TI  - 'Green diesel'--skin irritant properties of diesel oils compared to common
      solvents.

PMID- 8565504
TI  - Allergic contact dermatitis from erythromycin.

PMID- 8565505
TI  - Allergic contact dermatitis from anthrarobin.

PMID- 8565506
TI  - Towards a history of patch testing.

PMID- 8565507
TI  - Factors associated with early onset pneumonia in the severely brain-injured
      patient.
AB  - An analysis of 125 patients with closed head injury was completed in order to
      identify the risk factors involved in the development of early pneumonia.
      Pneumonia was diagnosed in 60% of the patients. Early pneumonia developed in
      47.8% of the patients. Brain-injured patients who developed early pneumonia were
      found to have a lower Glasgow Coma Scale (GCS) score. Early pneumonia was found
      more often in patients with swallowing disorders and evidence of aspiration.
      Patients who had been intubated in the field were found to be at greater risk for
      the development of early pneumonia than those intubated in the hospital. Patients
      with early pneumonia had prolonged intubation times, intensive care unit stays,
      and hospital stays. This study suggests that a GCS score less than 5, evidence
      for swallowing disorders and aspiration, and field intubation are risk factors
      for early pneumonia in the brain-injured patient.

PMID- 8565508
TI  - Strongyloidiasis masquerading as inflammatory bowel disease in a patient with
      lupus erythematosis: a case report.

PMID- 8565509
TI  - Primary lymphoproliferative disorders of the breast.
AB  - Primary breast lymphoproliferative disorders are rare lesions and include both
      the malignant lymphomas and the benign pseudolymphomas. We reviewed 4,491
      consecutive cases of breast cancer diagnosed and treated between 1973 and 1988.
      Patients with lymphoma in other sites and those with lymphomas limited to
      axillary nodes were excluded. RESULTS. Five patients (0.11%) presented with
      primary lymphoreticular lesions, of which three were primary non-Hodgkin's
      lymphoma and two were pseudolymphomas. Patients were followed clinically through
      to the present time or until death occurred. Surgical procedures included
      incisional or excisional biopsy in four patients and modified radical mastectomy
      in one. Two patients received chemo-therapy and one received radiotherapy. One
      patient with pseudolymphoma subsequently developed infiltrating ductal carcinoma
      of the same breast. Three patients with primary breast non-Hodgkin's lymphoma
      died within the follow-up period, with a mean survival of 33 months. CONCLUSIONS.
      We conclude that primary breast lymphoma is a rare and aggressive breast
      malignancy with a poor prognosis despite different treatment options.

PMID- 8565510
TI  - On-site adequacy assessments for image-directed fine needle aspirations: a study
      of 341 cases.
AB  - On-site adequacy assessments (OSAA) are reported to decrease the unsatisfactory
      and nondiagnostic rates of fine needle aspirations (FNAs). These have been
      routine in many institutions but were only recently introduced to our large
      teaching hospital. The results of FNAs performed in diagnostic radiology between
      January to December 1992 were compared to aspirations done by the same clinical
      staff during the first year (1993) after the addition of an on-site adequacy
      assessment service. In the year prior to OSAA, 154 FNAs were performed in
      diagnostic radiology and the material obtained was processed by a
      cytotechnologist. Of these, 89 (58%) cases were positive for malignant cells.
      Approximately half of these cases had confirmatory tissue biopsies processed in
      the surgical pathology department of our institution. The remaining 65 (42%) of
      cytology specimens were determined to be negative or nondiagnostic for
      malignancy. These canes either had no tissue follow-up or the tissue obtained was
      nondiagnostic. Before beginning OSAA, nine cases (6%) were interpreted as
      negative for malignancy, but subsequent tissue biopsies were malignant. There
      were no false positives during this time. Diagnostic sensitivity was 86% before
      OSAA. One hundred seventy-seven image directed FNAs were performed in the first
      year following the establishment of OSAA. Of these, 102 (58%) cases were
      interpreted as positive for malignant cells. About half of these patients went on
      to have confirmative tissue biopsies. Fifty-six (32%) cases were interpreted as
      negative for malignancy or nondiagnostic on FNA and follow-up tissue biopsies
      were also either negative or nondiagnostic. The false negative rate was 1% after
      OSAA and there were no false positives during this period. Diagnostic sensitivity
      was 98% after OSAA. In addition, the average overall number of passes per patient
      have decreased from 2.4 before OSAA to 1.6 after OSAA.

PMID- 8565511
TI  - The use of angiotensin converting enzyme inhibitors in asymptomatic patients with
      left ventricular dysfunction after myocardial infarction.

PMID- 8565512
TI  - Reform measures brought increased profits, not coverage.

PMID- 8565513
TI  - Liposomal prostaglandin E1 in acute respiratory distress syndrome: a placebo
      controlled, randomized, double-blind, multicenter clinical trial.
AB  - OBJECTIVE: To evaluate the safety and efficacy of liposomal prostaglandin E1 (TLC
      C-53) in the treatment of patients with the acute respiratory distress syndrome
      (ARDS). DESIGN: Randomized, prospective, multicenter, double-blind, placebo
      controlled, phase II clinical trial. SETTING: Eight community and university
      affiliated hospitals in the United States. PATIENTS: Twenty-five patients with
      ARDS. INTERVENTIONS: Patients were prospectively randomized in an unbalanced
      ratio within each site to receive either TLC C-53 (n = 17) or placebo (n = 8).
      Study drug was infused intravenously over 60 mins every 6 hrs for a 7-day period,
      starting at a dose of 0.15 micrograms/kg/hr. The dose was increased every 12 hrs
      until the maximal dose (3.6 micrograms/kg/hr) was attained, intolerance to
      further increases developed, or invasive monitoring was discontinued. Patients
      received standard, aggressive, medical/surgical care throughout the trial.
      MEASUREMENTS AND MAIN RESULTS: Outcome measurements were Pao2/FI0(2), dynamic
      pulmonary compliance, ventilator dependence on day 8, and 28-day all-cause
      mortality rate. At baseline, the distribution of variables describing Lung Injury
      Scores, Acute Physiology and Chronic Health Evaluation II scores, Pao2/FI0(2),
      pulmonary compliance, and time from onset of ARDS to first dose of study drug was
      similar between patients in the TLC C-53 and placebo treatment groups. On day 8,
      all eight patients given placebo required mechanical ventilation, while eight of
      17 patients given TLC C-53 were healthy enough to be removed from the ventilator
      (p = .03). Improvement in PaO2/FIO2 during the initial 8-day study period was
      greater in patients receiving TLC C-53. This trend achieved statistical
      significance on day 3, when the increase in PaO2/FIO2 from baseline was 82.5 +/-
      14.6 in the TLC C-53 group compared with 28.3 +/- 22.1 in the placebo group (p =
      .05). By day 8, lung compliance also increased from baseline significantly more
      in TLC C-53 patients than in placebo patients (5.7 +/- 1.7 vs -1.5 +/- 1.8 mL/cm
      H2O; p = .01). The 28-day mortality rate was 6% (1/17 patients) in the TLC C-53
      group and 25% (2/8 patients) in the placebo group (p = .23). Drug-related adverse
      events were reported in 82% of the patients receiving TLC C-53 compared with 38%
      of the placebo group, with half of the adverse events in the TLC C-53 group being
      localized infusion site irritation. TLC C-53 was hemodynamically well tolerated,
      with transient hypotension occurring in three patients. CONCLUSIONS: In patients
      with ARDS, TLC C-53 was associated with improved oxygenation, increased lung
      compliance, and decreased ventilator dependency.

PMID- 8565514
TI  - Enhanced recovery of brain electrical activity by adenosine 3',5'-cyclic
      monophosphate following complete global cerebral ischemia in dogs.
AB  - OBJECTIVE: To test the hypothesis that adenosine 3',5'-cyclic monophosphate
      (cAMP) or dibutyl-cAMP (a more lipid-soluble, less rapidly metabolized analog of
      cAMP) would improve recovery of cerebral electrical activity and metabolic
      function after transient global cerebral ischemia by improving cerebral blood
      flow during the reperfusion period. DESIGN: Randomized, controlled, prospective
      study. SETTING: University research laboratory. SUBJECTS: Twenty-five male beagle
      dogs. INTERVENTIONS: Nine control dogs received saline (20-mL/kg bolus and 0.01
      mL/kg/min) intravenously, beginning 25 mins before 12 mins of cerebral global
      ischemia (by aortic occlusion). The dogs in the experimental groups received
      either cAMP (40 mg/kg 25 mins before ischemia and 0.2 mg/kg/min throughout
      reperfusion, n = 7), or dibutyl-cAMP (6 mg/kg 25 mins before ischemia and 3 mg/kg
      at 60, 90, and 120 mins of reperfusion, n = 9). MEASUREMENTS AND MAIN RESULTS:
      Total and regional cerebral blood flow, cerebral oxygen consumption, and
      somatosensory evoked potentials were measured during 180 mins of reperfusion.
      Pretreatment with dibutyl-cAMP resulted in increased postischemic hyperemia at 30
      mins of reperfusion (e.g., whole brain: control 40 +/- 6; cAMP 56 +/- 9; dibutyl
      cAMP 67 +/- 10 mL/min/100 g [mean +/- SEM, p < .05 control vs. dibutyl-cAMP
      group]) but no difference in total cerebral blood flow or oxygen consumption
      during later points of reperfusion. All groups demonstrated rapid ablation of the
      amplitude of somatosensory evoked potentials during ischemia, with no difference
      between the groups. At 180 mins of reperfusion, somatosensory evoked potentials
      recovered to 28 +/- 4% of the preischemic baseline value in dogs treated with
      saline, whereas the somatosensory evoked potentials recovered to 58 +/- 4% of
      preischemic baseline value in the cAMP-pretreated group (p < .05), and to 70 +/-
      6% of preischemic baseline value in dogs treated with dibutyl-cAMP (p < .05).
      CONCLUSIONS: cAMP and dibutyl-cAMP improve recovery of cerebral electrical
      function after complete transient global cerebral ischemia. Although hyperemia
      was more prolonged in cAMP- and dibutyl-cAMP-treated dogs, there was no
      difference between groups in degree of postischemic delayed hypoperfusion.
      Therefore, we believe that the mechanism for cerebral protection afforded by cAMP
      and dibutyl-cAMP is not related to cerebral circulatory effects.

PMID- 8565515
TI  - Hypertonic saline does not improve cerebral oxygen delivery after head injury and
      mild hemorrhage in cats.
AB  - OBJECTIVES: To investigate the effects of hypertonic saline for resuscitation
      after mild hemorrhagic hypotension combined with fluid-percussion traumatic brain
      injury. Specifically, the effects of hypertonic saline on intracranial pressure,
      cerebral blood flow (radioactive microsphere method), cerebral oxygen delivery
      (cerebral oxygen delivery = cerebral blood flow x arterial oxygen content), and
      electroencephalographic activity were studied. DESIGN: Randomized, controlled,
      intervention trial. SETTING: University laboratory. SUBJECTS: Thirty-four mongrel
      cats of either sex, anesthetized with 1.0% to 1.5% isoflurane in nitrous
      oxide/oxygen (70:30). INTERVENTIONS: Anesthetized (isoflurane) cats were prepared
      for traumatic brain injury, and then randomly assigned to the following groups:
      moderate traumatic brain injury only (2.7 +/- 0.2 atmospheres [atm], group 1);
      mild hemorrhage (18 mL/kg) only, followed immediately by resuscitation with 10%
      hydroxyethyl starch in 0.9% saline in a volume equal to shed blood (group 2); or
      both traumatic brain injury (2.7 +/- 0.1 atm) and mild hemorrhage, followed
      immediately by replacement of a volume equal to shed blood of 10% hydroxyethyl
      starch in 0.9% saline (group 3); or 3.0% saline (group 4). MEASUREMENTS AND MAIN
      RESULTS: Data were collected at baseline, at the end of hemorrhage, and at 0, 60,
      and 120 mins after resuscitation (or at comparable time points in group 1).
      Intracranial pressure in group 1 was significantly increased by traumatic brain
      injury at the end of hemorrhage, immediately after resuscitation, and 60 mins
      after resuscitation (p < .02 vs. baseline). In group 2, intracranial pressure
      increased significantly only immediately after resuscitation (p < .0001 vs.
      baseline). Groups 3 and 4 exhibited higher, although statistically insignificant,
      intracranial pressure increases at 60 and 120 mins after resuscitation. During
      resuscitation, cerebral blood flow increased significantly (p < .02 vs. baseline)
      in the uninjured cats. In contrast, cerebral blood flow failed to increase during
      resuscitation in the cats subjected to traumatic brain injury before hemorrhage
      and resuscitation. Although cerebral oxygen delivery in group 2 decreased
      significantly immediately, 60 mins, and 120 mins after resuscitation (p < .001
      vs. baseline) both groups 3 and 4 had significantly lower cerebral oxygen
      delivery at 60 and 120 mins after resuscitation (p < .01 and p < .005,
      respectively, vs. group 1 at 60 mins after resuscitation, and p < .01 and p <
      .01, respectively, vs. group 1 at 120 mins after resuscitation). CONCLUSIONS:
      After a combination of hemorrhage and traumatic brain injury, neither 10%
      hydroxyethyl starch nor 3.0% hypertonic saline restored cerebral oxygen delivery.
      Although neither trauma alone nor hemorrhage alone altered
      electroencephalographic activity, the combination produced significant decreases
      in electroencephalographic activity at 60 and 120 mins after resuscitation in
      groups 3 and 4, suggesting that cerebral oxygen delivery is inadequately restored
      by either resuscitation fluid. Therefore, traumatic brain injury abolished
      compensatory cerebral blood flow increases to hemodilution, and neither
      hydroxyethyl starch nor 3.0% hypertonic saline restored cerebral blood flow,
      cerebral oxygen delivery, or electroencephalographic activity after hemorrhagic
      hypotension after traumatic brain injury.

PMID- 8565516
TI  - Burn injury alters beta-adrenergic receptor and second messenger function in rat
      ventricular muscle.
AB  - OBJECTIVES: The molecular pharmacologic bases for the attenuated cardiovascular
      and metabolic responses to catecholamines, after burn injury, have not been
      elucidated. In the present study, myocardial tissues were used as a model of beta
      adrenergic receptors to study burn injury-induced alterations in receptors and in
      signal transduction. DESIGN: Prospective study, randomized to treatment and
      control groups. SETTING: University-hospital research laboratory. SUBJECTS: Male
      Sprague-Dawley rats (180 to 210 g). INTERVENTIONS: A 50% body surface area burn
      or sham-burn was administered to the rats. MEASUREMENTS AND MAIN RESULTS:
      Myocardial membranes were isolated at 24 hrs, 7 days and 14 days after 50% body
      surface area scald or sham injury. (-)125I-iodocyanopindolol was used to assess
      maximal binding capacity and affinity of the beta-adrenergic receptor. Basal and
      stimulated concentrations of second messenger, cyclic adenosine monophosphate
      (cAMP), were also assessed. Production of cAMP during isoproterenol stimulation
      tested the integrity of the beta-adrenergic receptor-mediated signal
      transduction. Forskolin, which stimulates adenylate cyclase enzyme directly
      (bypassing the receptor and G protein) to produce cAMP, tested the efficacy of
      the enzyme itself. Maximal binding capacity was unaltered between the
      experimental and control groups, but the affinity (mean +/- SEM) was
      significantly decreased in burned animals at 7 days (125.4 +/- 15.5 picomoles
      [pmol]; p = .01) and at 14 days (216.7 +/- 50.7 pmol; p = .001) compared with
      controls (75.5 +/- 8.4 pmol). In different set experimental and control groups,
      basal concentrations of cAMP in myocardial membranes were significantly decreased
      in burned animals at 7 days (control 38.6 +/- 4.2 vs. 5.8 +/- 0.9 pmol/mg of
      protein/min; p = .003) and at 14 days (control 47.4 +/- 3.2 vs 28.3 +/- 6.6
      pmol/mg of protein/min; p = .002). The forskolin (direct)-stimulated synthesis of
      cAMP was decreased in burned animals at 24 hrs (control 339.0 +/- 40.5 vs. 214.4
      +/- 16.6 pmol/mg of protein/min; p = .01), at 7 days (control 289.0 +/- 34.4 vs.
      32 +/- 13.0 pmol/mg of protein/min; p = .01), and at 14 days (control 322.9 +/-
      28.6 vs. 137.0 +/- 46.1 pmol/mg of protein/min; p = .01). The isoproterenol or
      receptor-mediated stimulation of cAMP production was also significantly (p <
      .001) impaired in burned animals compared with controls at 24 hrs (control 134.7
      +/- 11.9 vs. 83.1 +/- 13.3 pmol/mg of protein/min), and at 14 days (control 128.2
      +/- 7.2 vs. 92.8 +/- 17.7 pmol/mg of protein/min). CONCLUSION: The etiology of
      the decreased responses in the myocardium to exogenous and endogenous beta
      adrenergic receptor agonists after burn injury may be attributed to decreased
      affinity for ligands, and also to impaired receptor-mediated signal transduction
      and to decreased adenylate cyclase enzyme activity, resulting in decreased basal
      and stimulated second messenger (cAMP) production.

PMID- 8565517
TI  - Adrenergic vasopressor agents and mechanical ventilation for the treatment of
      experimental septic shock.
AB  - OBJECTIVE: Vasopressor agents and mechanical ventilation are routine
      interventions for the treatment of sepsis complicated by hypotension. It was our
      hypothesis that such treatment singly or in combination increases the duration of
      survival. DESIGN: Prospective, randomized, controlled study. SETTING: University
      research laboratory. SUBJECTS: Thirty male Sprague-Dawley rats anesthetized with
      intraperitoneal injection of pentobarbital. INTERVENTIONS: Peritonitis was
      induced by cecal ligation and spillage of cecal contents into the abdominal
      cavity. The first phase of this study was performed on 15 spontaneously breathing
      Sprague-Dawley rats that were randomized to three groups of five animals each.
      One group received treatment with dopamine. The second group received
      norepinephrine. The third group received only the diluent as a placebo.
      Concentrations of the vasopressor agents were increased such that mean arterial
      pressure was maintained at approximately 80% of baseline values; the volumes
      infused were kept constant. For the second phase of this study, the grouping of
      animals and the techniques of study were identical, except that rats were
      mechanically ventilated. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure
      was best maintained with norepinephrine. However, no statistically significant
      differences in duration of survival, cardiac index, arterial blood lactate
      concentration, or arterial and venous PCO2 and PO2 values were identified between
      groups. With mechanical ventilation, survival was prolonged (p < .01). Survival
      was increased from an average of 291 mins to 342 mins with dopamine, from 257
      mins to 352 mins in placebo controls, and from 280 mins to 329 mins with
      norepinephrine. Again, no significant differences in hemodynamic and blood gas
      measurements, or in the duration of survival between vasopressor-treated and
      control animals were documented. CONCLUSIONS: No benefit or detriment was
      demonstrated when vasopressor agents were administered to sustain arterial
      pressure in the course of experimental peritonitis in this murine model of septic
      shock. This finding contrasted with highly significant prolongation of survival
      when animals were mechanically ventilated. There was no evidence that routine
      vasopressor therapy, under these controlled experimental conditions in rats,
      improved duration of survival.

PMID- 8565518
TI  - Nitric oxide synthase inhibition during experimental sepsis improves renal
      excretory function in the presence of chronically increased atrial natriuretic
      peptide.
AB  - OBJECTIVE: To test whether renal excretory function decreases after nitric oxide
      synthase inhibition during experimental hyperdynamic sepsis. DESIGN: Prospective,
      randomized, controlled animal trial. SETTING: Research laboratory at a large
      university medical center. SUBJECTS: Chronically instrumented Merino breed ewes
      (n = 18). INTERVENTIONS: Continuous infusion of Escherichia coli endotoxin (10
      ng/kg/min) for the experimental period of 32 hrs. One group received a bolus of
      the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (25
      mg/kg), after 24 hrs, and the remaining sheep were given the carrier, sodium
      chloride 0.9%. MEASUREMENTS AND MAIN RESULTS: The sheep developed a hyperdynamic
      cardiovascular response characterized by a decrease in systemic vascular
      resistance index (p < .05), and an increased cardiac index (p < .05) by 24 hrs.
      The sheep retained fluid, with creatinine clearance decreasing in the presence of
      chronically increased atrial natriuretic peptide. After the administration of N
      omega-nitro-L-arginine methyl ester, systemic vascular resistance index and
      cardiac index returned to baseline values, fluid balance normalized, and
      glomerular filtration rate increased (p < .05), while the control animals
      continued to retain fluid and their creatinine clearance continued to decrease.
      The concentrations of atrial natriuretic peptide did not differ significantly
      between groups after N omega-nitro-L-arginine methyl ester administration.
      CONCLUSIONS: In this ovine model of experimental hyperdynamic sepsis, renal
      excretory function decreases in the presence of chronically increased
      concentrations of atrial natriuretic peptide. Administration of the nitric oxide
      synthase inhibitor, N omega-nitro-L-arginine methyl ester, reverses the
      vasodilatory state, thereby improving fluid balance and glomerular filtration.

PMID- 8565519
TI  - Role of endothelin in the cardiovascular effects of diaspirin crosslinked and
      stroma reduced hemoglobin.
AB  - OBJECTIVES: Diaspirin crosslinked hemoglobin is a resuscitative solution with
      excellent oxygen-carrying capacity. Diaspirin crosslinked hemoglobin produces an
      immediate increase in blood pressure and marked regional circulatory changes in
      rats and pigs. Our objective was to determine the role of endothelin in the
      cardiovascular actions of diaspirin crosslinked hemoglobin (modified) and
      (unmodified) stroma reduced hemoglobin solutions. DESIGN: Prospective, randomized
      comparison of cardiovascular effects of diaspirin crosslinked and stroma reduced
      hemoglobin in control rats and in rats pretreated with cyclo(D-Asp-Pro-D-Val-Leu
      D-Trp) (BQ-123), an endothelin-A receptor antagonist. SETTING: Research
      laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Modified, highly
      purified, and heat pasteurized (diaspirin crosslinked) and unmodified (stroma
      reduced) hemoglobin in control (untreated) and BQ-123 (5 mg/kg/hr iv)-treated
      rats. MEASUREMENTS AND MAIN RESULTS: Infusion of stroma reduced hemoglobin (400
      mg/kg iv) in control rats produced an increase in blood pressure (43%) and total
      peripheral resistance (65%) without any change in heart rate, cardiac output, and
      stroke volume. Stroma reduced hemoglobin decreased blood flow to the kidneys and
      liver, increased blood flow to the heart, and had no effect on blood flow to the
      brain, gastrointestinal tract, spleen, musculoskeletal system, skin, and
      mesentery and pancreas. Infusion of stroma reduced hemoglobin in rats treated
      with BQ-123 (5 mg/kg/hr iv) increased the blood pressure to a similar degree when
      compared with control rats, but the increase in total peripheral resistance was
      significantly attenuated. The stroma reduced hemoglobin-induced decrease in blood
      flow to the kidneys and liver was significantly attenuated in BQ-123-treated rats
      as compared with control rats. However, the stroma reduced hemoglobin-induced
      increase in blood flow to the heart of BQ-123-treated rats was similar to the
      increase in control rats. Infusion of diaspirin crosslinked hemoglobin (400 mg/kg
      iv) produced increases in blood pressure (81%), cardiac output (36%), stroke
      volume (30%), and total peripheral vascular resistance (45%), along with
      increases in blood flow to the heart, spleen, gastrointestinal tract, and skin of
      control rats. The blood flows to the brain, kidneys, liver, musculoskeletal
      system, and mesentery and pancreas were not altered by diaspirin crosslinked
      hemoglobin in control rats. The increases in blood pressure, cardiac output,
      stroke volume, and total peripheral vascular resistance by diaspirin crosslinked
      hemoglobin were significantly blocked in BQ-123-treated rats as compared with
      control rats. The increases in blood flow to the heart, spleen, and skin by
      diaspirin crosslinked hemoglobin were significantly blocked in BQ-123-treated
      rats as compared with control rats. Diaspirin crosslinked hemoglobin produced an
      increase in the blood flow to the brain and a decrease in blood flow to the
      kidney and musculoskeletal system of BQ-123-treated rats as compared with control
      rats. Blood plasma endothelin-1-like immunoreactivity was found to be
      significantly increased after treatment with diaspirin crosslinked hemoglobin or
      stroma reduced hemoglobin. CONCLUSIONS: The endothelin-A receptor antagonist, BQ
      123, could attenuate the systemic hemodynamic and regional circulatory effects of
      diaspirin crosslinked hemoglobin and stroma reduced hemoglobin. However, the
      increase in blood flow to the heart induced by stroma reduced hemoglobin could
      not be attenuated by BQ-123.

PMID- 8565520
TI  - Respiratory and cardiac function in children after acute hypoxemic respiratory
      failure.
AB  - OBJECTIVE: To examine the pulmonary and cardiac function of children who survived
      an episode of acute hypoxemic respiratory failure. DESIGN: Descriptive cohort
      analysis. SETTING: Pediatric clinical research center of a university hospital.
      PATIENTS: Utilizing the criteria of PaO2 < 75 torr (< 10 kPa) with an FIO2 of >
      0.5 while intubated, bilateral diffuse pulmonary infiltrates on chest radiograph,
      and exclusion of cardiogenic pulmonary edema, 147 patients were identified during
      the 6-yr period from July 1, 1986 to August 1, 1993. Fifty patients survived to
      discharge and 37 were alive at the time of follow-up. Fourteen patients were
      eventually entered into the study. INTERVENTIONS: The study patients were given a
      test battery consisting of a questionnaire specific for cardiopulmonary status, a
      physical examination, a chest radiograph, electrocardiography, echocardiography
      with detailed examination of the pulmonary circulation, pulse oximetry, complete
      blood count, and serum chemistries and pulmonary function testing with
      bronchoprovocation in selected patients. MEASUREMENTS AND MAIN RESULTS: The 14
      follow-up patients were evaluated an average of 23 +/- 23 months (range 3 to 66)
      following intensive care unit discharge. No child reported a significant
      alteration in lifestyle or limitation of activities. Physical examinations were
      generally unremarkable. The room air oxyhemoglobin saturation was > or = 0.98 in
      all patients. Comparison of chest radiographs at the time of follow-up with those
      chest radiographs during the period of critical illness showed marked but not
      complete improvement in all. Electrocardiograms and echocardiograms showed new
      evidence of left ventricular hypertrophy in one child. The right ventricular
      preejection period to ejection time ratio was normal in all subjects. Eleven
      patients completed spirometry. Four patients were normal and the other patients
      had evidence of restrictive or obstructive disease either at baseline or after
      bronchoprovocation challenge. Ten children had lung volume measurements. Five
      children were normal, two showed increased volumes consistent with obstruction,
      and three showed decreased volumes indicative of restriction. Four of seven
      patients showed evidence of decreased diffusion capacity. Six of seven patients
      with evidence of abnormal pulmonary function had a positive response to
      bronchodilator administration. CONCLUSIONS: Although pediatric survivors of acute
      hypoxemic respiratory failure perceive neither a limitation in lifestyle nor
      chronic pulmonary morbidity, careful examination of the cardiopulmonary system
      demonstrates a significant number with abnormal chest radiographs and
      abnormalities in pulmonary function. These children require careful follow-up and
      may benefit from use of a bronchodilator.

PMID- 8565521
TI  - Cerebral blood flow and carbon dioxide reactivity in neonates during venoarterial
      extracorporeal life support.
AB  - OBJECTIVES: a) To determine if cerebral blood flow is symmetric after internal
      carotid artery and ipsilateral internal jugular vein ligation in infants during
      venoarterial extracorporeal life support. b) To determine the cerebral CO2
      reactivity (delta cerebral blood flow/delta torr CO2) of neonates during
      venoarterial extracorporeal life support and its correlation to
      neurodevelopmental outcome. DESIGN: Prospective, clinical study. SETTING:
      University hospital pediatric intensive care unit. PATIENTS: Fourteen neonates
      with respiratory failure who were receiving venoarterial extracorporeal life
      support. INTERVENTIONS: PaCO2 was altered by adjusting the CO2 gas flow through
      the membrane oxygenator. Cerebral blood flow was measured over both parietal
      temporal regions at three PaCO2 values using xenon-133 clearance methodology.
      Cerebral blood flow measurements were made early (< or = 12 hrs of extracorporeal
      life support, n = 10) or late (> or = 48 hrs of extracorporeal life support, n =
      10). In six of 14 infants, both early and late cerebral blood flow rates were
      measured. PaO2, mean arterial pressure, pump flow rate, and temperature were
      stable during each study period. Neurodevelopmental outcome was assessed in the
      neonatal follow-up clinic. MEASUREMENTS AND MAIN RESULTS: Right and left
      hemispheric cerebral blood flow rates were significantly correlated with each
      other during early and late extracorporeal life support (p = .0001; r2 = .91).
      Overall, hemispheric cerebral blood flow was statistically symmetric. There was
      no association of CO2 reactivity (delta cerebral blood flow/delta torr PCO2,
      range 0.04 to 1.36 mL/min/100 g/torr) with short-term neurodevelopmental outcome.
      Infants with normal neurodevelopmental outcome had variable CO2 reactivity (range
      0.04 to 0.67 mL/min/100 g/torr). Normal short-term neurodevelopmental outcome was
      observed in two infants with cerebral blood flow of < 10 mL/min/100 g.
      CONCLUSIONS: Hemispheric cerebral blood flow was symmetric in infants during
      early and late venoarterial extracorporeal life support. Some subgroups showed a
      trend toward decreased right hemispheric cerebral blood flow, but the small
      number of patients limited interpretation of this finding. CO2 reactivity and
      cerebral blood flow were highly variable in this population, and were not
      predictive of short-term neurodevelopmental outcome. Stressed neonates with
      extremely low cerebral blood flow rates may have relatively normal short-term
      neurodevelopmental outcome after venoarterial extracorporeal life support.

PMID- 8565522
TI  - Initial experience with partial liquid ventilation in pediatric patients with the
      acute respiratory distress syndrome.
AB  - OBJECTIVE: Liquid ventilation with perfluorocarbon previously has not been
      reported in pediatric patients with respiratory failure beyond the neonatal
      period. We evaluated the technique of partial liquid ventilation in six pediatric
      patients with the acute respiratory distress syndrome of sufficient severity to
      require extracorporeal life support (ECLS). DESIGN: This study was a
      noncontrolled, phase I/II experimental study with a single group pretest/posttest
      design. SETTING: All studies were performed at a tertiary, pediatric referral
      hospital at the University of Michigan Medical School. PATIENTS: Six pediatric
      patients, from 8 wks to 5 1/2 yrs of age, with severe respiratory failure
      requiring ECLS to support gas exchange. INTERVENTIONS: After 2 to 9 days on ECLS,
      perfluorocarbon was administered into the trachea until the dependent zone of
      each lung was filled. The initial administered was 12.9 +/- 2.3 mL/kg (range 5 to
      20). Gas ventilation of the perfluorocarbon-filled lungs (partial liquid
      ventilation) was then performed. The perfluorocarbon dose was repeated daily for
      a total of 3 to 7 days, with a cumulative dose of 45.2 +/- 6.1 mL/kg (range 30 to
      72.5). MEASUREMENTS AND MAIN RESULTS: All measurements of native gas exchange
      were made during brief periods of discontinuation of ECLS and include PaO2 and
      the alveolar-arterial oxygen gradient, P(A-a)O2. Static pulmonary compliance,
      corrected for weight, was also measured directly. The mean PaO2 increased from 39
      +/- 6 to 92 +/- 29 torr (5.2 +/- 0.8 to 12.2 +/- 3.9 kPa) over the 96 hrs after
      the initial dose (p = .021 by repeated-measures analysis of variance). The
      average P(A-a)O2 decreased from 635 +/- 10 to 499 +/- 77 torr (84.7 +/- 1.3 to
      66.5 +/- 10.3 kPa) over the same time period (p = .059), while the mean static
      pulmonary compliance (normalized for patient weight) increased from 0.12 +/- 0.02
      to 0.28 +/- 0.08 mL/cm H2O/kg (p = .01). All six patients survived. Complications
      potentially associated with partial liquid ventilation were limited to
      pneumothoraces in two of six patients. CONCLUSIONS: Perfluorocarbon may be safely
      administered into the lungs of pediatric patients with severe respiratory failure
      on ECLS and may be associated with improvement in gas exchange and pulmonary
      compliance.

PMID- 8565523
TI  - Toward a theory regarding the pathogenesis of the systemic inflammatory response
      syndrome: what we do and do not know about cytokine regulation.
AB  - OBJECTIVES: The systemic inflammatory response syndrome (SIRS) is the massive
      inflammatory reaction resulting from systemic mediator release that may lead to
      multiple organ dysfunction. The objective of this review article is to analyze
      the roles of cytokines, cytokine production, and the relationship of cytokine
      production to the development of SIRS. DATA SOURCES: Previous research and
      clinical studies related to cytokines and their relationship to SIRS. STUDY
      SELECTION: From the studies reviewed, three critical questions are addressed.
      First, what is the definition of increased cytokine concentrations? Second, what
      other systemic illnesses besides sepsis can alter cytokine concentrations? Third,
      what are the right cytokines to measure? DATA SYNTHESIS: This article postulates
      a three-stage development of SIRS, in which stage 1 is a local production of
      cytokines in response to an injury or infection. Stage 2 is the protective
      release of a small amount of cytokines into the body's circulation. Stage 3 is
      the massive systemic reaction where cytokines turn destructive by compromising
      the integrity of the capillary walls and flooding end organs. CONCLUSIONS: While
      cytokines are generally viewed as a destructive development in the patient that
      generally leads to multiple organ dysfunction, cytokines also protect the body
      when localized. It will be necessary to study the positive effects of cytokines
      while also studying their role in causing SIRS. It will also be important to
      investigate the relationship between cytokines and their blockers in SIRS.

PMID- 8565524
TI  - Early enteral formula administration.

PMID- 8565525
TI  - Early enteral formula administration.

PMID- 8565526
TI  - Propofol bashing: the time to stop is now!

PMID- 8565527
TI  - Long-term effects of selective decontamination on antimicrobial resistance.

PMID- 8565528
TI  - Propofol vs. midazolam for sedation.

PMID- 8565529
TI  - Esophageal balloon manometry and weaning from mechanical ventilation.

PMID- 8565530
TI  - Mortality risk prediction of sepsis.

PMID- 8565531
TI  - Metabolic stress and dobutamine.

PMID- 8565532
TI  - Progress in central venous access.

PMID- 8565533
TI  - Causes of hypercarbia with oxygen therapy in patients with chronic obstructive
      pulmonary disease.
AB  - OBJECTIVES: To compare data derived from a computer model of the pulmonary
      circulation with data from a case series of patients with chronic obstructive
      pulmonary disease (COPD). To evaluate the specific factors contributing to CO2
      retention due to oxygen therapy in patients with acute exacerbations of COPD.
      DESIGN: Data from a computer model of the pulmonary circulation were compared
      with a previous case series. PATIENTS: Patient data were derived from previous
      case series. INTERVENTIONS: Simulated application of oxygen therapy. MEASUREMENTS
      AND MAIN RESULTS: The computer model of the pulmonary circulation generates data
      comparable with those data from a series of patients with COPD treated with
      supplemental oxygen and permits identification of the causes for hypercarbia.
      Therapy with supplemental oxygen alters hypoxic pulmonary vasoconstriction and
      modulates the Haldane effect, resulting in changes in physiologic deadspace.
      CONCLUSION: Changes in physiologic deadspace are sufficient to account for the
      hypercarbia developed by patients with acute exacerbations of COPD when treated
      with supplemental oxygen.

PMID- 8565534
TI  - Bronchoalveolar oxyradical inflammatory elements herald bronchopulmonary
      dysplasia.
AB  - OBJECTIVES: To quantify oxyradical inflammatory markers in serial endotracheal
      tube aspirates obtained from premature neonates at risk for developing
      bronchopulmonary dysplasia, and to correlate these parameters with clinical
      manifestations of the disease. DESIGN: Prospective cohort study. SETTING:
      Tertiary neonatal intensive care unit. PATIENTS: Twenty-eight intubated,
      premature infants, with 15 infants displaying simple respiratory distress
      syndrome and 13 infants eventually developing bronchopulmonary dysplasia.
      INTERVENTIONS: Endotracheal tube aspirates were collected and clinical severity
      scores were calculated longitudinally from an inception cohort during the first
      week of life. Diagnosis of bronchopulmonary dysplasia by standard criteria was
      recorded at 30 days of life. Various biochemical analyses related to pulmonary
      oxyradical stress were determined on endotracheal tube aspirates and were
      normalized according to the magnitude of serum/aspirate urea ratios. The
      demographic, illness severity, and biochemical characteristics of infants with
      simple respiratory distress syndrome and those characteristics of infants
      developing bronchopulmonary dysplasia were evaluated by masked comparison.
      MEASUREMENTS AND MAIN RESULTS: Populations of respiratory distress syndrome and
      bronchopulmonary dysplasia infants could be differentiated during the first week
      of life by means of the following parameters: gestational age; birth weight;
      Score of Neonatal Acute Physiology; Neonatal Therapeutic Intervention Scoring
      System; epithelial lining fluid leukocytes; elastase; myeloperoxidase; xanthine
      oxidase and catalase enzyme activities; and total sulfhydryls. CONCLUSIONS:
      Infants with simple respiratory distress syndrome could be segregated from those
      infants who developed bronchopulmonary dysplasia by the magnitude of the
      epithelial lining fluid oxyradical inflammation markers. While infants developing
      bronchopulmonary dysplasia typically exhibited increased concentrations of these
      markers during the first week of life, those infants with simple respiratory
      distress syndrome displayed low, uniform, or decreasing values of these markers
      over this interval. Infants developing bronchopulmonary dysplasia demonstrate an
      early pulmonary inflammatory response, and one key aspect of this response
      involves various oxyradical-generating systems.

PMID- 8565535
TI  - The herculean task of treating acute respiratory distress syndrome.

PMID- 8565536
TI  - Magnesium repletion and its effect on potassium homeostasis in critically ill
      adults: results of a double-blind, randomized, controlled trial.
AB  - OBJECTIVES: The aims of this study were to evaluate the safety and efficacy of
      magnesium replacement therapy and to determine its effect on potassium retention
      in hypokalemic, critically ill patients. DESIGN: A prospective, double-blind,
      randomized, placebo-controlled trial. SETTING: A surgical intensive care unit
      (ICU). PATIENTS: A total of 32 adult surgical ICU patients were admitted to the
      study on the basis of documented hypokalemia (potassium of < 3.5 mmol/L) within
      the 24-hr period before entering the study. Patients were randomized to receive
      either placebo (n = 15) or magnesium sulfate (n = 17). One patient from each
      group was excluded from the study due to failure to complete the full series of
      doses. INTERVENTIONS: Patients received a "test dose" of either magnesium sulfate
      (2 g, 8 mmol) or placebo (5% dextrose in water) infused over 30 mins every 6 hrs
      for eight doses. The next schedule test dose was held if hypermagnesemia
      (magnesium of > 2.8 mg/dL [> 1.15 mmol/L]) was documented at any time during the
      study. Routine replacements of potassium and magnesium continued during the
      duration of the study, when clinically indicated, for serum potassium
      concentrations of 3.5 mmol/L or serum magnesium concentrations of < 1.8 mg/dL (<
      0.74 mmol/L). MEASUREMENTS AND MAIN RESULTS: Age, weight, and Acute Physiology
      and Chronic Health Evaluation II scores were recorded on entry into the study.
      Just before administration of each test dose, blood was drawn for magnesium and
      potassium, bicarbonate, pH, and glucose determinations, and an aliquot of the
      preceding 6 hrs urine collection was sent for magnesium and potassium
      determinations. Serum calcium, phosphate, urea nitrogen, and creatinine
      concentrations were measured daily. The amounts of magnesium and potassium
      administered via parenteral nutrition, tube feeding, and replacement infusions
      were calculated for each 6-hr interval. The amounts of magnesium and potassium
      excreted in the urine were similarly assessed. The groups showed no differences
      with regard to age, weight, Acute Physiology and Chronic Health Evaluation II
      scores, or initial serum magnesium concentration. Initial potassium, bicarbonate,
      pH, calcium, phosphate, glucose, blood urea nitrogen, and creatinine values were
      not different between groups. Patients receiving magnesium sulfate showed a
      statistically significant increase in serum magnesium concentration at 6 hrs when
      compared with placebo, as well as with itself at time 0 (p < .0001), a difference
      maintained throughout the study. Compared with the placebo group, the total
      amount of elemental magnesium administered was significantly greater in the
      treatment group (1603 +/- 124 vs. 752 +/- 215 mg [65.7 +/- 5.8 vs. 30.8 +/- 8.8
      mmol], p < .0001), as was urine magnesium excretion (1000 +/- 156 vs. 541 +/- 68
      mg [41.0 +/- 6.4 vs. 22.2 +/- 2.8 mmol] p < .0001). However, the net magnesium
      balance (total magnesium in - total urine magnesium) was significantly more
      positive in the treatment group (612 +/- 180 vs. 216 +/- 217 mg [25.1 +/- 7.4 vs.
      8.9 +/- 8.9 mmol], p < .005). The treatment and control groups had the same serum
      potassium concentrations and did not receive different amounts of potassium (245
      +/- 39 vs. 344 +/- 45 mmol, respectively, p = .06), although the treatment group
      required less potassium replacement/6 hrs by 30 hrs compared with itself at time
      0 (p < .05). Despite the same serum potassium values, the net potassium balance
      for 48 hrs was positive in the treatment group (+ 72 +/- 32 mmol) and negative in
      the control group (-74 +/- 95 mmol, p < .05). There were no complications
      associated with the magnesium sulfate administration. CONCLUSIONS: Magnesium
      sulfate administered according to the above regimen safety and significantly
      increases the circulating magnesium concentration. Despite greater urine
      magnesium losses in the treatment group, this group exhibited significantly
      better magnesium retention.

PMID- 8565537
TI  - Liquid breathing: stretching the technological envelope.

PMID- 8565538
TI  - Use of predicted risk of mortality to evaluate the efficacy of anticytokine
      therapy in sepsis. The rhIL-1ra Phase III Sepsis Syndrome Study Group.
AB  - OBJECTIVES: To investigate a novel anticytokine therapy in patients with sepsis
      syndrome, and the relationship between a patient's baseline mortality risk and
      survival benefit. DESIGN: Data from a recent phase III, double-blind, placebo
      controlled, multicenter clinical trial with patients randomized to three
      treatment arms: an intravenous loading dose of recombinant human interleukin-1
      receptor antagonist (rhIL-1ra) or placebo, followed by a continuous infusion of
      rhIL-1ra (1.0 mg/kg/hr, or 2.0 mg/kg/hr), or placebo for 72 hrs. SETTING: Sixty
      three investigative centers in eight countries. PATIENTS: The study population
      consisted of 893 patients: 302 placebo patients; 298 patients treated with 1.0
      mg/kg/hr of rhIL-1ra; and 293 patients treated with 2.0 mg/kg/hr of rhIL-1ra.
      MEASUREMENTS AND MAIN RESULTS: An independent, sepsis-specific, log-normal
      regression model that predicts the risk of mortality over 28 days was applied to
      all patients enrolled into the rhIL-1ra sepsis study. The ability of the
      Predicted Risk of Mortality model to predict 28-day mortality in the placebo
      patients was determined and the relationship between mortality risk and efficacy
      of rhIL-1ra was investigated. The trial data were also analyzed using two other
      risk-assessment models for comparison with Predicted Risk of Mortality. A
      significant increase in survival time was demonstrated for all patients treated
      with rhIL-1ra (n = 893, p < .02 Predicted Risk of Mortality log-normal), but
      patients with a Predicted Risk of Mortality of < 24% derived little benefit.
      Retrospective examination of time-to-death data demonstrated that rhIL-1ra
      reduced risk of death in the first 2 days for patients with > or = 24% Predicted
      Risk of Mortality (n = 580, p < .005 Predicted Risk of Mortality log-normal).
      This same effect was not present in patients with a Predicted Risk of Mortality
      of < 24% on entry into the study. The Predicted Risk of Mortality model predicted
      a 28-day mortality rate of 35% for placebo patients compared with 34% observed
      and accurately stratified patients along the full range of risks. There was a
      wide distribution of individual patient risks for 28-day mortality for all
      patients, as well as within categorical subgroups, such as shock and organ system
      dysfunction. Two alternate risk models were assessed and the Acute Physiology
      Score of Acute Physiology and Chronic Health Evaluation III also demonstrated a
      statistically significant survival benefit for rhIL-1ra (p = .04 Predicted Risk
      of Mortality log-normal) for all patients treated. CONCLUSIONS: Using an
      appropriate analytic model, a statistically significant increase in survival time
      from rhIL-1ra was measured. A direct relationship was found between a patient's
      Predicted Risk of Mortality at study entry to efficacy of rhIL-1ra. Individual
      risk or severity assessment may be a useful tool for evaluating the clinical
      benefit of new therapeutic approaches to sepsis and for monitoring outcomes at
      the bedside.

PMID- 8565539
TI  - Factors affecting the performance of the models in the Mortality Probability
      Model II system and strategies of customization: a simulation study.
AB  - OBJECTIVES: To examine the impact of hospital mortality and intensive care unit
      (ICU) size on the performance of the Mortality Probability Model II system for
      use in quality assessment, and to examine the ability of model customization to
      produce accurate estimates of hospital mortality to characterize patients by
      severity of illness for clinical trials. DESIGN: Prospective evaluation of model
      performance, using retrospective data. SETTING: Data for the simulation were
      assembled from six adult medical and surgical ICUs in Massachusetts and New York.
      PATIENTS: Consecutive admissions (n = 4,224) to the Massachusetts and New York
      ICUs were studied. The mortality rate in the database was 18.7%. INTERVENTIONS: A
      computer simulation of several different hospital mortality rates and ICU sample
      sizes, using a multicenter database of consecutive ICU admissions, was utilized.
      We simulated 20 different mortality rates by randomly changing the outcomes at
      hospital discharge from "survived" to "deceased" and from "deceased" to
      "survived". Four sample size simulations used 75%, 50%, 25%, and 10% of the
      database. Ten replications of each mortality rate and samples size were
      constructed, and model calibration and discrimination were assessed for each
      replication. Model coefficients were customized, using logistic regression.
      MEASUREMENTS AND MAIN RESULTS: Vital status at hospital discharge was the outcome
      measure among the ICU patient population. Model performance was assessed using
      the Hosmer-Lemeshow C statistic for calibration, and the area under the receiver
      operating characteristic curve for discrimination. Goodness-of-fit tests and
      receiver operating characteristic curve areas demonstrated that the models were
      sensitive to differences in hospital mortality, indicating that they are useful
      quality assurance tools. Goodness-of-fit tests were more sensitive than the
      receiver operating characteristic curve areas. The further the hospital mortality
      rate diverged from the original rate, the worse the performance of the model.
      Sample size had an impact on these results. The smaller the sample size, the less
      likely the model was to perform poorly. Model coefficients were successfully
      customized to demonstrate that improved model performance can be achieved when
      necessary for clinical trial stratification. CONCLUSION: Mortality Probability
      Model II models can be used to assess quality of care in ICUs, but the size of
      the sample should be considered when assessing calibration and discrimination.

PMID- 8565540
TI  - Hazards with both determining and utilizing oxygen consumption measurements in
      the management of critically ill patients.

PMID- 8565541
TI  - Simplified Therapeutic Intervention Scoring System: the TISS-28 items--results
      from a multicenter study.
AB  - OBJECTIVES: To validate a simplified version of the Therapeutic Intervention
      Scoring System, the TISS-28, and to determine the association of TISS-28 with the
      time spent on scored and nonscored nursing activities. DESIGN: Prospective,
      multicenter study. SETTING: Twenty-two adult medical, surgical, and general Dutch
      intensive care units (ICUs). PATIENTS: A total of 903 patients consecutively
      admitted to the ICUs. INTERVENTIONS: TISS-28 was constructed from a random sample
      of 10,000 records of TISS-76 items. The respective weights were calculated using
      multivariable regression analysis through the origin; TISS-76 scores were used as
      predicted values. Cross validation was performed in another random sample of
      10,000 records and the scores of TISS-76 were compared with those scores obtained
      with TISS-28 (r = .96, r2 = .93). Nursing activities in the ICU were inventoried
      and divided into six categories: a) activities in TISS-28; b) patient care
      activities not in TISS-28; c) indirect patient care (activities related to but
      not in direct contact with the patient, such as contact with family, maintaining
      supplies); d) organizational activities (e.g., meetings, trainee supervision,
      research); e) personal activities (for the nurse him/herself, such as taking a
      break, going to the bathroom); f) other. During a 1-month period, TISS-76 and
      TISS-28 scores were determined daily from the patient's records by independent
      raters. During a 1-wk period, all of the nurses on duty scored their activities
      using a method called "work sampling." MEASUREMENTS AND MAIN RESULTS: The
      analysis of validation included 1,820 valid pairs of TISS-76 and TISS-28 records.
      The mean value of TISS-28 (28.8 +/- 11.1) was higher (p < .00) than that value of
      TISS-76 (24.2 +/- 10.2). TISS-28 explained 86% of the variation in TISS-76 (r =
      .93, r2 = .86). "Work sampling" generated 10,079 registrations of nursing
      activities, of which 5,530 could be matched with TISS-28 records. Samples were
      taken from medical (19.3%), surgical (19.1%), and general (61.6%) ICUs. Of these
      samples, 51.1% originated from university hospitals, 35.8% from hospitals with >
      500 beds, 7.1% from hospitals with 300 to 500 beds, and 5.8% from hospitals with
      < 300 beds. Samples were scored in the morning (43.0%), evening (32.9%), and
      night shifts (24.1%). This sample of work activities was divided into four
      groups, according to their matched TISS scores (0 to 20, 20 to 35, 35 to 60, and
      > 60 points). In the successive groups of TISS scores, there was a significant
      increase in the proportion of time spent on the activities scored with TISS-28.
      In the lower TISS score group (0 to 20 points), there was a significantly larger
      proportion of time allocated to patient care activities not in TISS-28. There was
      no significant difference in the proportion of the time spent when associating
      indirect patient care and organizational activities with the level of TISS score.
      There was a significant decrease in the proportion of time spent on personal
      activities in the successive groups of TISS scores. The mean time spent per shift
      with personal activities varied between 1 hr and 40 mins (group 0 to 20 points
      TISS), and 1 hr and 16 mins (group > 60 points TISS). Significantly more time was
      used for patient care activities during the evening shift than during the day or
      the night shift. Conversely, nurses spent significantly less time on activities
      regarding their personal care during the evening shift. The time consumed for the
      activities of indirect patient care did not differ significantly among the three
      shifts. A typical nurse was capable of delivering work equal to 46.35 TISS-28
      points per shift (one TISS-28 point equals 10.6 mins of each nurse's shift).
      CONCLUSIONS: The simplified TISS-28 explains 86% of the variation in TISS-76 and
      can therefore replace the original version in the clinical practice in the ICU.
      Per shift, a typical nurse is capable of delivering nursing activities equal to
      46 TISS-28 points.

PMID- 8565542
TI  - Frequency of variable measurement in 16 pediatric intensive care units: influence
      on accuracy and potential for bias in severity of illness assessment.
AB  - OBJECTIVES: We evaluated: a) whether the frequency of variable measurement could
      influence the performance of the Pediatric Risk of Mortality (PRISM) score; b)
      whether measurement frequency of physiologic variables varied between individual
      pediatric intensive care units (ICUs), and c) if so, how much of this variability
      could be attributed to institution-level and patient-level factors. DESIGN:
      Prospective cohort. SETTING: Sixteen pediatric ICUs, chosen for their diversity.
      PATIENTS: Consecutive admissions (n = 5,415). INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: First, the measurement frequency of the 14 physiologic
      variables in the PRISM score was included in the logistic regression model
      predicting mortality risk. Measurement frequency was not significant, alone or in
      its interaction with the PRISM score. Second, the presence or absence of
      measurement of each physiologic variable was included in the logistic model using
      indicator variables; none was significant. Finally, the contribution of the
      individual pediatric ICUs and patient factors in explaining the variability in
      the frequency of physiologic variable measurement were investigated with linear
      regression analysis. In this analysis, the separation of severity of illness from
      measurement frequency was accomplished by computing the PRISM score from the
      first 4 hrs and measurement frequencies from hours 5 through 24. Overall, 70.22%
      (r2) of the variability of measurement frequency could be explained by the
      factors included in the linear regression model. The individual ICUs accounted
      for a total of only 6.23% of the explained variability and no individual hospital
      accounted for > 1.44% of the variability. Other variables positively correlated
      with measurement frequency included the presence or absence of a pediatric
      intensivist, and whether the institution was a children's hospital or not.
      Variables negatively correlated with measurement frequency included larger ICUs
      and house officers assigned to the ICU. CONCLUSIONS: Although measurement
      frequency is associated with unit-level factors, their contribution to the
      overall variability is small and unlikely to influence the accuracy or
      reliability of the PRISM score. It is unlikely that there are routine biases
      associated with differences in measurement frequency of PRISM variables within
      the spectrum of care practices that now exist.

PMID- 8565543
TI  - Prediction of three outcome states from pediatric intensive care.
AB  - OBJECTIVE: To develop a method based on admission day data for predicting patient
      outcome status as independently functional, compromised functional, or dead.
      DESIGN: Prospectively acquired development and validation samples. SETTING: A
      pediatric intensive care unit located in a tertiary care center. PATIENTS:
      Consecutive admissions (n = 1,663) for predictor development, and consecutive
      admissions (n = 1,153) for predictor validation. METHODS: Pediatric Risk of
      Mortality score, baseline Pediatric Overall Performance Category score, age,
      operative status, and primary diagnosis classified into ten organ systems and
      nine etiologies were recorded at the time of intensive care unit admission.
      Predictor was developed by stepwise polychotomous logistic regression analysis
      for the outcome functional, compromised, and dead. Model fit was evaluated by chi
      square statistics; prediction performance was measured by the area under the
      receiver operating characteristic curve, and classification table analysis of
      observed vs. predicted outcomes. MEASUREMENTS AND MAIN RESULTS: The resulting
      predictor included Pediatric Risk of Mortality, baseline Pediatric Overall
      Performance Category, operative status, age, and diagnostic factors from four
      systems (cardiovascular, respiratory, neurologic, gastrointestinal), and six
      etiologies (infection, trauma, drug overdose, allergy/immunology, diabetes,
      miscellaneous/undetermined). Its application to the validation sample yielded
      good agreement between the total number expected and the observed outcomes for
      each state (chi-square = 3.16, 2 degrees of freedom, p = .206), with area indices
      of 0.96 +/- 0.01 for discrimination of fully functional vs. the combination of
      the two poor outcome states (compromised or death), and 0.94 +/- 0.02 for
      discrimination of fully or compromised functional vs. death. The 3 x 3
      classification resulted in correct classification rates of 83.2%, 74.4%, and
      81.3%, for the outcomes functional, compromised, and death, respectively.
      CONCLUSIONS: Prediction of three outcome states using physiologic status,
      baseline functional level, and broad-based diagnostic groupings at admission is
      feasible and may improve the relevance of quality of care assessment.

PMID- 8565544
TI  - Oxygen consumption calculated from the Fick equation has limited utility.
AB  - OBJECTIVE: To determine if oxygen consumption (VO2) calculated using the Fick
      relationship (calculated VO2) determines total body VO2 accurately and precisely
      enough to employ this method during clinical assessment of oxygen transport.
      DESIGN: Methods comparison, using repeated measures during four physiologic
      states: normal heart/normal lungs, heart failure/normal lungs, normal heart/acute
      lung injury, heart failure/acute lung injury. SETTING: University research
      laboratory. SUBJECTS: Thirteen adult Yucatan pigs. INTERVENTIONS: Oleic acid
      induced acute lung injury; heart failure was induced with a continuous infusion
      of esmolol. MEASUREMENTS AND MAIN RESULTS: Calculated VO2 was determined by
      multiplying thermodilution cardiac output by the arterialvenous oxygen content
      difference in anesthetized, spontaneously breathing animals. Conditions were
      tightly controlled so that calculated VO2 would be as accurate as possible.
      "True" VO2 was measured simultaneously with a water-sealed spirometer (spirometry
      VO2). Calculated VO2 and spirometry VO2 were determined and analyzed during the
      four physiologic states listed above. Pooled data also were evaluated. Mean
      spirometry VO2 and calculated VO2 differed significantly during all four
      physiologic states and when data were pooled (spirometry VO2 273 +/- 70,
      calculated VO2 178 +/- 58 mL/min; p < .01). Calculated VO2 consistently
      underestimated spirometry VO2, as demonstrated by the large, positive bias in
      pooled data (95 +/- 59 mL of oxygen/min) and in the four physiologic states.
      Linear regression of data from all four states yielded slopes that were
      indistinguishable from 1, but y intercepts that varied from -152 to +182. For
      pooled data, the following equation was used: calculated VO2 = 0.5 x (spirometry
      VO2 + 46); r2 = .35. Precision in pooled data was 22% of the mean spirometry VO2.
      Data analysis for the four physiologic states demonstrated results similar to
      those results obtained when data were pooled. CONCLUSIONS: Even in a tightly
      controlled, clinical simulation in the laboratory, calculated VO2 from the Fick
      relationship systematically underestimated VO2 measured with a water-sealed
      spirometer. If true VO2 changes, the magnitude and direction of change will be
      reflected by calculated VO2 but with approximately 20% error in the absolute
      value. Heart failure, acute lung injury, and their combination did not affect the
      accuracy of calculated VO2. Therefore, calculating VO2 using the Fick
      relationship is too inaccurate to be used for research purposes. Because
      assessment of the directional change of VO2 may be clinically useful, calculated
      VO2 can be employed with discretion during clinical oxygen transport evaluation,
      bearing in mind the calculation's inherent imprecision.

PMID- 8565545
TI  - Spirometric versus Fick-derived oxygen consumption: which method is better?
AB  - OBJECTIVE: Oxygen consumption (VO2) is often measured in critically ill patients
      using the Fick equation: VO2 = cardiac output x arterial-venous oxygen content
      difference. To determine if this method is accurate, it was compared with a
      spirometric technique. DESIGN: Prospective study. SETTING: University laboratory.
      SUBJECTS: Nineteen large adult pigs. INTERVENTIONS: Cardiac output, measured with
      bolus thermodilution technique, and arterial and venous oxygen content values,
      determined with the galvanic fuel cell method, were used to determine VO2 with
      the Fick equation. The spirometrically determined VO2 was the rate of
      disappearance of oxygen from a water-sealed spirometer. Dobutamine and labetalol
      were titrated to vary VO2 (range 204 to 584 mL/min). MEASUREMENTS AND MAIN
      RESULTS: The bias between the Fick and spirometrically determined VO2 values was
      58 mL/min. The precision (SD of the bias) between the Fick and spirometrically
      determined Vo2 was 35 mL/min. Fick-derived Vo2 was greater than Vo2 measured
      spirometrically. The correlation coefficient was 0.90. CONCLUSIONS; Despite all
      attempts to reduce measurement error, there was an unexplained difference in Fick
      derived and spirometrically measured Vo2. Therefore, I feel that the two methods
      are not interchangeable, and that calculations of Vo2 using the Fick method
      should be used cautiously when therapeutic maneuvers are based on these data.

PMID- 8565547
TI  - Immunology of silicones. Proceedings of a workshop. Bethesda, Maryland, March 13
      14, 1995.

PMID- 8565546
TI  - Single breath CO2 analysis: description and validation of a method.
AB  - OBJECTIVES: To evaluate the performance of a newly developed single breath CO2
      analysis station in measuring the airway deadspace in a lung model (study 1), and
      then to quantify the bias and precision of the physiologic deadspace measurement
      in a surfactant-depleted animal model (study 2). DESIGN: A prospective bench
      validation of a new technique of airway deadspace measurement using a criterion
      standard (study 1); a prospective, animal cohort study comparing a new technique
      of physiologic deadspace measurement with a reference method (Bohr-Enghoff
      method) (study 2). SETTING: A bench laboratory and animal laboratory in a
      university-affiliated medical center. SUBJECTS: A lung model (study 1), and adult
      sheep with induced surfactant deficiency (saline lavage) (study 2). METHODS: The
      single breath CO2 analysis station consists of a mainstream capnometer, a
      variable orifice pneumotachometer, a signal processor, and computer software with
      capability for both on- and off-line data analysis. Study 1: We evaluated the
      accuracy of the airway deadspace calculation using a plexiglass lung model. The
      capnometer and pneumotachometer were placed at the ventilator Y-piece with
      polyvinyl chloride tubing added to simulate increased airway deadspace. Segments
      of tubing were sequentially removed during each testing session to simulate
      decreasing deadspace. The calculated airway deadspace was derived from the single
      breath CO2 plot and compared with the actual tubing volume using least-squares
      linear regression and paired t-tests. Study 2: The accuracy of the physiologic
      deadspace measurement was examined in a saline-lavaged animal model by comparing
      the physiologic deadspace calculated from the single breath CO2 analysis station
      with values obtained using the Enghoff modification of the Bohr equation:
      deadspace/tidal volume ratio = (PaCO2-mixed expired PCO2)/PaCO2. MEASUREMENTS AND
      MAIN RESULTS: Study 1: Thirty-six measurements of calculated airway deadspace
      were made and compared with actual circuit deadspace during four different
      testing conditions. Measured airway deadspace correlated significantly with
      actual circuit deadspace (r2 = .99). The proportional error of the method was 
      0.8% with a 95% confidence interval from -3.6% to 1.9%. Study 2: A total of 27
      pairs of measurements in four different animals were available for analysis. The
      derived physiologic deadspace/tidal volume ratio significantly correlated with
      the value obtained using the Bohr-Enghoff method (r2 = .84). The bias and
      precision of our physiologic deadspace calculation were .02 and .02,
      respectively, and the mean percent difference for the physiologic deadspace
      calculated from the single breath CO2 analysis station was 2.4%. CONCLUSIONS: Our
      initial experience with the single breath CO2 analysis station indicates that
      this device can reliably provide on-line evaluation of the single-breath CO2
      waveform. In particular, estimation of the airway and physiologic deadspace under
      a variety of testing conditions was consistently within 5% of actual values. We
      feel that with further application and refinement of the technique, single breath
      CO2 analysis may provide a noninvasive, on-line monitor of changes in pulmonary
      blood flow.

PMID- 8565548
TI  - Induction of type II collagen arthritis in the DA rat using silicone gel as
      adjuvant.
AB  - The Dark Agouti (DA) rat has been shown recently to have a high susceptibility
      for developing arthritis when challenged with either heterologous or homologous
      collagen II mixed with mineral oil, or with mineral oil challenge alone. This
      study determined the arthritogenic potential of silicone gel by either mixing it
      with bovine collagen II (BII) or by injecting silicone gel alone in DA rats. The
      incidence of collagen induced arthritis was as follows: PBS group- 0/10, silicone
      gel group- 4/10, and IFA group- 8/9. Anti-BII antibodies were formed in most of
      the rats treated with either silicone gel or IFA and these groups of rats showed
      a positive DTH reaction. The PBS treated rats were negative for both anti-BII
      antibodies and DTH reaction. The incidence of arthritis formation in rats
      injected with silicone gel alone was 0/10, while the IFA injected rats showed an
      incidence of 8/10. Silicone gel taken from a commercial breast implant thus is
      capable of mediating collagen induced arthritis in the DA rat. However, silicone
      gel alone does not appear to be arthritogenic.

PMID- 8565549
TI  - The adjuvancy of silicones: dependency on compartmentalization.
AB  - Studies have been conducted in mice (B6C3F1) and rats (Sprague Dawley, Fischer
      344) to investigate the adjuvancy potential of silicone mammary gel and the low
      molecular weight silicone fluid, octamethylcyclotetrasiloxane (D4). Dependent on
      the experimental conditions employed, a divergent data profile emerges. If the
      antigen (bovine serum albumin, BSA) is emulsified with either the gel or the D4
      prior to intramuscular immunization, an amplified anti-BSA IgG antibody response,
      as measured by multipoint ELISA methodology, is noted over the 8 week measurement
      period. In parallel studies, a variety of non-silicone personal care ingredients
      (lanolin, white mineral oil, isopropyl palmitate) were also capable of amplifying
      this humoral response relative to the non-adjuvant phosphate buffered saline
      control. These observations are consistent with the empirical knowledge that
      hydrophobic substances tend to augment immune responses. However, under
      conditions in which the antigen is not blended with the silicone prior to
      immunization, normal immune responses are noted. In short (10 day) and long (180
      day) term gel implant studies, the optimal IgM and IgG antibody responses, as
      determined in the antibody forming cell assay, were equivalent between the gel
      implanted and control animals. Moreover, under similar exposure conditions, no
      adjuvancy was noted in the three Host Resistance models (B16F10 Melanoma,
      Listeria monocytogenes, and Streptococcus pneumoniae) tested. Antibody forming
      cell studies conducted after 28 days of oral or inhalation exposure to D4 have
      also yielded responses similar to the non-silicone exposed vehicle controls.
      Collectively, these data suggest that in the absence of premixing the antigen
      with the silicone test material, there does not appear to be any silicone induced
      adjuvant response.

PMID- 8565550
TI  - The adjuvant effect of silicone gel and silicone elastomer particles in rats.
AB  - This study examines the adjuvant properties of silicone oil, silicone gel and
      silicone elastomer using a foreign antigen, bovine serum albumin (BSA). Seventy
      male Harlan Sprague-Dawley rats, approximately 250 grams each, were divided into
      7 groups: A- incomplete Freund's adjuvant (IFA) with BSA; B- silicone oil with
      BSA; C- IFA/silicone oil with BSA; D- 50% silicone gel/50% silicone oil with BSA;
      E- silicone oil/1000 microns elastomer particles with BSA; F- silicone oil/500
      microns elastomer particles with BSA; G- saline with BSA. Rats were implanted
      intramuscularly with mixtures or emulsions of the above described treatment
      materials. Cardiac punctures were performed on days 0, 14, 28, 42, and 55. Serum
      IgG antibody response to BSA was determined by enzyme-linked immunosorbent assay
      (ELISA). Rats were sacrificed on day 55 and sections of the injection sites were
      collected and stained for histopathologic evaluation. The results demonstrated
      that silicone gel functions as a potent immunologic adjuvant as measured by a
      heightened IgG antibody response to BSA. In contrast silicone elastomer particles
      have no apparent adjuvant effect as determined by the low anti-BSA antibody
      levels in these treatment groups throughout the course of the study.
      Histologically, silicone gel and silicone elastomer elicit a moderate to severe
      "foreign body" granulomatous inflammatory response at the injection site.
      Silicone oil elicits mild or no local inflammatory response.

PMID- 8565551
TI  - Silicone degradation reactions.

PMID- 8565552
TI  - Silicone gel and octamethylcyclotetrasiloxane potentiate antibody production to
      bovine serum albumin in mice.
AB  - Earlier studies, in the rat, have shown that silicone gel acts as a potent
      adjuvant for antibody production against bovine serum albumin (BSA). The purpose
      of the present study is to determine whether components of the silicone breast
      implant (silicone oil, silicone gel, and octamethylcyclotetrasiloxane [D4])
      potentiate the antibody response to BSA in mice. Groups of ten A/J mice received
      a single subcutaneous injection of 0.1 ml of BSA emulsified with the following:
      a) silicone preparations, b) incomplete Freund's adjuvant, or c) saline alone.
      Antibodies to BSA were measured using an enzyme-linked immunosorbant assay. The
      results indicate that both D4 and the silicone gel potentiate antibody production
      to BSA in mice. Known adjuvants have been shown to induce autoimmune syndromes in
      animal models. Whether silicones can act in a similar mechanism is still unclear.

PMID- 8565553
TI  - Fibrogenic and other biological effects of silica.

PMID- 8565554
TI  - Macrophages in host defense mechanisms.

PMID- 8565555
TI  - Structure and function of natural antibodies.
AB  - Natural antibodies arise independently of known antigenic stimulation, are mostly
      IGM, polyreactive, and are generally encoded by V genes in germline
      configuration. Polyreactive IgM natural antibodies are produced by mainly B-1
      cells which account for most of the B cell repertoire in the fetus and neonate,
      and possibly play a major role in the development and physiology of the human B
      cell repertoire. Although endowed with self-reactivity, natural antibodies also
      bind exogenous antigens [73, 74]. Exposure to environmental antigens is not
      necessary for the emergence of natural antibody-producing cell precursor clones
      to exogenous antigens, as suggested by the significant population of B cells
      capable of producing antibodies to a variety of bacterial antigens in germ-free
      animals. Because of their ability to bind a variety of exogenous antigens,
      including those on bacteria and viruses, natural antibodies play a major role in
      the primary line of defense against infections. A central issue related to the
      understanding of the physiopathologic roles of natural antibodies is whether
      precursors of cells producing natural antibodies, B-1a and B-1b lymphocytes, are
      capable of undergoing an antigen-driven clonal selection process, thereby
      producing autoantibodies with a high affinity for the selecting antigen. In this
      respect, we have clearly established that B-1 cells can express a hypermutation
      mechanism similar to that of conventional (B-2) cells. Furthermore, we have shown
      by gene shuffling, site-directed mutagenesis, and in vitro human Ig gene
      expression, that the main structural correlate for antibody polyreactivity is
      provided by the somatically generated H chain CDR3. We have also shown that this
      Ig V region provides the main structural correlate for antigen-binding in
      monoreactive antigen-induced autoantibodies. These findings in the human are at
      the basis of our proposed structure-function model in which the antigen binding
      features of the germline template antibody are dictated by the somatically
      generated H chain CDR3, and perhaps, but at a lower degree, L chain CDR3; the
      point-mutation changes underlying the antigen-driven affinity maturation process
      would impact mainly the Ig V gene encoded segments. This structure-function model
      is being tested in our laboratory by analyzing the antigen binding activity of
      somatically mutated polyreactive autoantibodies that have been structurally
      reverted to their original putative unmutated configuration. Precise
      identification of the Ig gene and/or somatic recombination products mediating
      recruitment of unmutated B cell clonotypes, as well as those that are
      preferentially modified by an antigen-dependent selection process, should further
      our understanding of the mechanisms that shape the B cell repertoire in
      development and disease.

PMID- 8565556
TI  - Antibodies to cholesterol: biological implications of antibodies to lipids.
AB  - Injection of silicone gel or silicone oil intraperitoneally into BALB/c mice
      induced the formation of antibodies that reacted by ELISA with highly purified
      crystalline cholesterol and, to a much lesser extent, antibodies that reacted
      with a phospholipid (dimyristoyl phosphatidylglycerol). Although IgM and IgG
      antibodies to cholesterol were detected, the titers of IgG antibodies were low
      when compared with IgM. The titers of IgM antibodies to cholesterol in certain
      sera exhibited activities that reached baseline values at dilutions as high as
      1:5000, thus making them equivalent to titers that have been previously published
      for ascites fluid containing murine monoclonal antibodies to cholesterol. The
      antibodies to cholesterol induced by silicone compounds are indistinguishable in
      their binding to crystalline cholesterol from naturally-occurring antibodies to
      cholesterol in normal human serum. They are also indistinguishable from
      antibodies induced by a proposed vaccine to cholesterol that is currently in late
      preclinical development for prevention of hypercholesterolemia in humans. The
      anti-cholesterol vaccine, which consists of liposomes heavily laden with
      cholesterol as an antigen and lipid A as an adjuvant, induces antibodies that
      react with low density lipoproteins (LDL) and opsonize them for removal by liver
      macrophages. It appears that silicone gel or silicone oil causes recruitment and
      adsorption of cholesterol at the injection site, and also serves as an adjuvant
      that may have immunostimulant properties similar to lipid A for inducing
      antibodies to lipids. Antibodies to lipids such as cholesterol or phospholipids
      are not harmful to intact cell membranes because of steric hindrance from
      surrounding lipids and larger macromolecules that block binding of the
      antibodies.

PMID- 8565557
TI  - Silicone-induced T cell proliferation in mice.

PMID- 8565558
TI  - Silicone-induced modulation of natural killer cell activity.
AB  - Current controversy regarding the effects of silicone gel mammary implants on the
      immune system has led to increased focus on the potential biological activity of
      silicone materials. Studies were undertaken in the B6C3F1 mouse to evaluate the
      immunotoxicological effects of the following components of a mammary gel
      prosthesis: polydimethylsiloxane fluid, silicone gel, elastomer shell and a
      polyurethane implant cover. Material was implanted subcutaneously (s.c.) for
      either 10 or 180 days. The only toxicological or immunological parameter which
      differed from control values was the natural killer (NK) cell activity in gel
      implanted mice. In these animals, basal NK activity was decreased. NK activity
      was comparably inhibited in female Fischer 344 rats implanted with silicone gel
      following short term (14 or 30 days) as well as chronic (1 year) exposure. The
      response was variable in both the rat and mouse. Host resistance to B16F10
      melanoma in the mouse is known to be related to NK activity. Despite suppression
      of NK activity following gel implantation, host resistance was unaltered.
      Inhibition of NK activity by the administration of anti-asialo GM1 indicated that
      resistance was not adversely affected until NK activity was decreased by 40 to
      50%. As with basal NK activity, augmented NK activity was inhibited in gel
      implanted rats when compared to controls. Administration of
      polyinosinic:polycytidylic acid to gel implanted rats resulted in an increase of
      approximately 65% in NK activity compared to gel implanted controls. This level
      of augmented NK activity was significantly less than the level of augmented NK
      activity in vehicle implanted animals where 100% enhancement in NK activity was
      noted. The results of these studies indicate that (1) NK cytolytic activity is
      altered in two animal models, the mouse and rat, although the results were
      variable, that (2) the level of suppression noted in the mouse is ineffective
      when compared to the level of suppression required to alter host resistance to
      B16F10 melanoma and that (3) the gel implanted animals exhibit a suppressed
      response to NK augmentation.

PMID- 8565559
TI  - HLA typing in women with and without silicone gel-filled breast implants.

PMID- 8565560
TI  - T cell-mediated immune response to silica in silicone breast implant patients.

PMID- 8565561
TI  - Immunohistopathology and T cell receptor gene expression in capsules surrounding
      silicone breast implants.

PMID- 8565562
TI  - Macrophage-silicone interactions in women with breast prostheses.

PMID- 8565563
TI  - Chemical, physical and mechanical analysis of explanted breast implants.
AB  - The chemical and biomechanical properties of explanted implants whose time of
      implantation ranged from zero to 21 years were measured. The properties appear to
      decrease with time. However it is important to note that proper controls have yet
      to be tested. The consistency of the gel varied considerably with manufacturer
      and date of manufacture. The data will be correlated with control samples when
      they become available. The data are consistent with the hypothesis that in some
      instances, the gel does affect the cross-linking, i.e., strength, of the silicone
      rubber shell. At the present time only a limited number of samples have been
      tested in this on-going program. One of our major objectives, to determine the
      influence of the physiological environment of the human body on the durability of
      the silicone implant, has yet to be quantified.

PMID- 8565564
TI  - Microscopic techniques and histologic findings in silicone mammary implant
      capsules and regional paranodal tissues.

PMID- 8565565
TI  - Antinuclear antibodies in apparently healthy women with breast implants.

PMID- 8565566
TI  - Silicone binding immunoglobulins in human sera.
AB  - We have evaluated two recently published test procedures for demonstrating
      antibodies to silicone. Positive control serum samples provided to us by the
      original authors were positive in our hands, using the methods described.
      However, serum samples from patients with certain connective tissue diseases but
      no history of silicone implants were also positive. The question of silicone
      specific antibodies remains unresolved.

PMID- 8565567
TI  - Autoantibodies in patients with silicone implants.
AB  - We assessed the prevalence of autoantibodies in women with silicone implants and
      controls. Five hundred consecutive patients with silicone implants, 25 age
      matched normal women, 25 women with silicone implants and no rheumatic symptoms,
      and 100 women with fibromyalgia were tested. Immunofluorescence antinuclear
      antibodies (ANA) were performed using HEp-2 cells. Subtype autoantibodies were
      performed by enzyme-linked immunoassay and Western blot. ANA tests were positive
      in 30% of patients with silicone implants and rheumatic symptoms, 8% of age
      matched normal women, 28% of women with silicone implants without clinical
      symptoms, and 25% of women with fibromyalgia and no silicone implants. The
      predominant ANA pattern was speckled (55%). ANA subtype testing was positive in
      4.8% of patients and none of the controls. We conclude that a larger proportion
      of women with silicone implants have autoantibodies compared to age-matched
      asymptomatic women suggesting immune activation in women with silicone implants.

PMID- 8565568
TI  - Clinical and laboratory features of patients with scleroderma and silicone
      implants.
AB  - We reviewed the available clinical and laboratory data from 56 patients with
      scleroderma and silicone implants from the English medical literature and 19
      cases which have not been previously reported. The average age of onset of
      scleroderma was 43.6 +/- 10 years (range 20-73). Patients had silicone implants
      for an average of 9 +/- 4 years prior to the development of scleroderma (range 1
      32). Most patients had limited scleroderma (41%). Twenty three percent had
      intermediate scleroderma and 36% had diffuse scleroderma. Clinical findings
      included: Raynaud's phenomenon in 77%, esophageal dysfunction in 53%, and
      pulmonary involvement in 47%. Cardiac and renal involvement were uncommon.
      Antinuclear antibodies by immunofluorescence were found in 83 percent of
      patients. The immunofluorescence pattern was speckled in 53%, centromere in 31%
      and nucleolar in 9%. Other antibodies (Scl-70, RNP, SSA/Ro, PM-Scl) were found in
      only a small proportion of patients. A clinical, serologic and immunogenetic
      comparison of patients with silicone implants and scleroderma and patients with
      idiopathic scleroderma is needed to better understand the pathogenesis of this
      disorder.

PMID- 8565569
TI  - Re-evaluation of autoantibodies and clinical overview of silicone-related
      disorders.

PMID- 8565570
TI  - Development of scleroderma-like syndrome in Tsk/+ mice is not enhanced by
      silicone administration.
AB  - The possible role of silicone in the pathogenesis of a scleroderma-like syndrome
      is still unresolved. It has been proposed that silicone escaping from breast
      implants potentiates the progression of the disease. To clarify whether silicone
      enhances development of fibrotic skin lesions and autoantibodies, we tested its
      effect on tight skin (TSK/+) mice. TSK/+ mice spontaneously develop skin fibrosis
      and characteristic autoantibodies which resemble human scleroderma. The results
      of the present study indicate that silicone administration does not enhance
      development of skin fibrosis nor synthesis of autoantibodies to RNA polymerase
      and topoisomerase in TSK/+ mice.

PMID- 8565571
TI  - Silica, silicon and silicones ... unraveling the mystery.

PMID- 8565572
TI  - Comparative epitope mapping of antibodies to collagen in women with silicone
      breast implants, systemic lupus erythematosus and rheumatoid arthritis.
AB  - Previous work has shown that women with silicone gel breast implants have an
      increased frequency of autoantibodies to collagen types I and II. 70 women
      without a specific autoimmune disease, using criteria of the American College of
      Rheumatology, but who had silicone breast implants were studied for the presence
      of serum antibodies to native and denatured human types I and II collagen by
      ELISA. 82 women with systemic lupus erythematosus (SLE), 94 women with rheumatoid
      arthritis (RA), and 133 healthy controls were also studied. There was a high
      frequency of autoantibodies to collagen in each of the groups when compared to
      the healthy controls. The specificities of these antibodies were found to differ
      markedly when examined by immunoblotting using peptides derived by cyanogen
      bromide digestion of the collagens. Sera from women with silicone implants
      reacted with multiple peptides of type I collagen in an individual-specific
      manner, but sera from women with SLE or RA reacted weakly with a restricted range
      of peptides. Against type II collagen, sera from women with RA reacted strongly
      with multiple peptides, while sera from women with silicone implants or SLE
      reacted only weakly or not at all. The patterns of reactivity against collagens
      by sera from women with silicone implants suggest that silicone can act as an
      adjuvant to enhance the immunogenicity of type I collagen.

PMID- 8565573
TI  - The prevalence of autoantibodies in symptomatic and asymptomatic patients with
      breast implants and patients with fibromyalgia.

PMID- 8565574
TI  - Monocyte/macrophage infiltrates in the salivary glands of women with silicone
      breast implants.

PMID- 8565575
TI  - Novel anti-silicone surface-associated antigen antibodies (anti-SSAA(x)) may help
      differentiate symptomatic patients with silicone breast implants from patients
      with classical rheumatological disease.
AB  - The frequency of novel autoreactive antibodies to silicone surface associated
      antigens (anti-SSAA(x)) was measured in healthy control patients, symptomatic
      patients with breast implants, asymptomatic patients with breast implants, and
      control patients with classical rheumatological diseases. The frequencies of
      elevated anti-SSAA(x) antibodies in 310 symptomatic breast implant patients were
      17.4% anti-SSAA(fn), 12.9% anti-SSAA(col1), and 7.4% anti-SSAA(col3) and 7.1%
      anti-SSAA(fbgn) [Normal (n = 173) = 0.6% for all four tests] (p < .005). In 11
      asymptomatic breast implant patients, the frequencies of elevated values for the
      same anti-SSAA's were 0%, 9%, 0%, and 0% respectively, while in 50 patients with
      rheumatoid arthritis, the frequencies were 4%, 0%, 6% and 2% respectively. The
      anti-SSAA(x) profile for symptomatic patients with breast implants was different
      than the profile for control healthy patients (p < .005 on all eight tests) but
      differed significantly by two measures, anti-SSAA(fbgn) and anti-SSAA(col3), from
      the profile for the 19 patients with systemic lupus erythematosus. We conclude
      that anti-SSAA(x) antibodies levels in symptomatic patients with breast implants
      are elevated, that the antibodies are associated with symptoms, and that they
      differ both qualitatively and quantitatively from healthy controls, asymptomatic
      patients with breast implants, and symptomatic patients with classical
      rheumatological diseases.

PMID- 8565576
TI  - Laboratory studies in breast implant patients: ANA positivity, gammaglobulin
      levels, and other autoantibodies.
AB  - Silicone polymers when used in augmentation prosthesis in breast surgery have
      been associated in the medical literature with various systemic clinical
      manifestations and abnormal laboratory testing suggestive of an atypical
      autoimmune disease. The most frequently cited abnormal test result is the
      antinuclear antibody. The literature regarding this test is reviewed in general,
      and then specific previous studies analyzed. The present study then compares the
      rate of positive antinuclear antibody tests in a case series of 3380 breast
      implant recipients with historical normal controls, and finds a six-fold increase
      in relative risk of a positive test. Analysis of the data show that this
      increased tendency is at least partially a function of duration of implant
      exposure to a significant degree (p < 0.001), and the same data shows it is not
      patient age related. Possible explanations of this phenomenon are discussed,
      including animal studies suggesting that silicone serves as an adjuvant, and
      therefore might have an effect on immune tolerance in the subject population.

PMID- 8565577
TI  - Is the risk of multiple myeloma increased in patients with silicone implants?

PMID- 8565578
TI  - Multiple myeloma in women with silicone breast implants. Serum immunoglobulin and
      interleukin-6 studies in women at risk.

PMID- 8565579
TI  - Silicone gel implants and monoclonal gammopathies: three cases of multiple
      myeloma and the prevalence of multiple myeloma and monoclonal gammopathy of
      undetermined significance.

PMID- 8565580
TI  - Monoclonal gammopathy of undetermined significance.

PMID- 8565581
TI  - The National Cancer Institute Silicone Implant/Multiple Myeloma Registry.

PMID- 8565582
TI  - The epidemiology of monoclonal gammopathy of unknown significance: a review.

PMID- 8565583
TI  - Silicon and silicone levels in patients with silicone implants.
AB  - Although a potential link between silicone gel breast implants and autoimmune
      connective tissue disease has been suggested, none has been proven. The potential
      role of silicone as an immune adjuvant remains very controversial. Currently
      available techniques do not easily allow precise measurements of silicone in
      tissues. However, all compounds containing silicon (which would include silicone)
      can be measured accurately. The present study was designed to measure silicon
      levels in the fibrous capsules of patients with silicone-gel breast implants,
      saline breast implants and silicone inflatable penile prostheses. Baseline
      control silicon levels were obtained from the breast tissue of patients
      undergoing breast reduction, who had no exposure to breast implants. All silicon
      measurements were carried out using atomic absorption spectrometry with a
      graphite furnace. The mean silicon levels in 16 breast tissue control samples
      from 8 patients undergoing breast reduction varied from 0.046 to 0.742
      micrograms/g dry weight, with the median mean being 0.0927. The median silicon
      level in capsules from 6 patients with saline implants was 7.7 micrograms/g
      (range 36.6). The median silicon level in capsules from 5 patients with silicone
      inflatable penile prostheses was 19.5 micrograms/g (range 34.8). Although the
      levels of silicon in capsules of patients with saline breast prostheses and
      penile implants were higher than in control samples, they were much lower than
      those from the capsules of the 58 gel implants (median 9979 micrograms/g). Of the
      58 silicone gel breast implants (from 20 patients with bilateral implant removal
      and 18 patients with unilateral removal) which had been inserted from 1974 to
      1990, 28 were intact, 8 had pinhole leaks, and 22 were ruptured. Median capsule
      silicon levels and ranges for all 58 implants, for intact only, for leaking, and
      for ruptured were: 9979 (152,000), 10,477 (88,703), 6592 (65,396), and 9922
      (152,387) micrograms/g respectively. There were no significant differences in
      silicon levels associated with implant status, duration in situ, or year of
      implantation. Capsule contracture was not associated with higher levels of
      capsule silicon. Capsule silicon levels were about 10(6) times higher than
      previously assayed blood silicon levels. This may be because silicone released
      from implants remains localized in capsular tissue, or because blood-borne
      silicone is quickly excreted. Using 29Si nuclear magnetic resonance spectroscopy,
      no detectable silicone was found in the blood of 7 control women and 7 women with
      silicone-gel implants (5 with known implant rupture).

PMID- 8565584
TI  - Plasmacytoma development in mice injected with silicone gels.
AB  - Silicone gels derived from commercially obtained implants induce plasmacytomas in
      60-70% of highly susceptible BALB/cAn.DBA/2-Idh1-Pep3 congenic mice. In contrast,
      dimethylpolysiloxane (DMPS) silicone oils with viscosities of 5, 1000 and 12,500
      cs fail to elicit these tumors. 1000 cs vinylmethylpolysiloxane is also inactive.
      Silicone gels, in contrast to the oils, induce a highly inflammatory silicone
      granuloma. Silicone gels contain chemical components not found in the oils. The
      chemical component responsible for inducing the permissive environment for
      plasmacytoma formation has not yet been identified. Silicone gels are well
      tolerated for long periods of time in mice without adverse effects other than
      plasmacytoma formation. The response to different gel preparations varies; some
      are associated with relatively rapid formation of plasmacytomas resembling that
      seen with pristane, while in others the plasmacytoma formation is extended nearly
      over a two year period.

PMID- 8565585
TI  - The association of augmentation mammoplasty with connective tissue disease,
      including systematic sclerosis (scleroderma): a meta-analysis.

PMID- 8565586
TI  - The prevalence of breast implants among women in the United States.
AB  - Estimates of the number of women with breast implants have varied from less than
      one million to over three million. Most of these appear to be extrapolations from
      either industry production figures or reports of surgical procedures. In late
      1989 under contract to the Dow Corning Corporation, Market Facts, Inc. conducted
      a mail survey of 40,000 households selected to be representative of the
      population of the United States. They received responses from 70.7%. Based upon
      the data collected, 8.08 per 1,000 women in the United States reported ever
      having had some type of breast implant. Approximately 60% of the procedures had
      been done for cosmetic reasons. Most of the women were White (94.6%) and rates
      were highest in the South or West. Although younger women were more likely to
      have had implants for augmentation and older women for reconstruction
      presumptively following breast cancer surgery, the largest prevalences for either
      of the two procedures were in the 45 to 54 year old age group. Breast implant
      prevalence also increased in direct proportion to household income with the
      largest increases being related to cosmetic augmentation. Based upon the data
      collected in this survey, the total number of women in the United States in late
      1989 who had ever had breast implants was estimated to be 815,700 (95% confidence
      interval: 715,757-924,729).

PMID- 8565587
TI  - Epidemiology of autoimmune and immunological diseases in association with
      silicone implants: is there an excess of clinical disease or antibody response in
      population-based or other "controlled" studies?

PMID- 8565588
TI  - Detection of silicone migration and biodegradation with NMR.

PMID- 8565589
TI  - Serum silicon levels are elevated in women with silicone gel implants.
AB  - The metabolic fate of silicone gel leaked into the body from an implant is
      unknown. In this study, serum from 72 women with silicone gel breast implants and
      55 control women was blindly assayed by inductively coupled plasma atomic
      emission spectroscopy (ICP-AES) for elemental silicon. Samples were processed
      using materials free of silicon. The mean silicon level in controls was 0.13 +/-
      0.07 mg/l (range 0.06-0.35 mg/l), while in implant patients, the mean was
      significantly higher at 0.28 +/- 0.22 mg/l (range 0.06-0.87 mg/l) (P < 0.01,
      Student's t-test with correction for unequal variances). Using the mean of the
      control group + 2 SD as a cutoff for normal range (0.27 mg/l), 25/72 (34.7%)
      implant patients exceeded this value, compared with 2/55 (3.6%) controls. There
      was no significant correlation between past rupture of one or both implants,
      current rupture at the time of the blood draw or the number of years with
      implants and silicon levels. The results suggest that elevations of serum silicon
      are seen in many women with silicone gel breast implants. The kinetics of this
      elevation and the actual chemical species of the measured silicon remain to be
      determined.

PMID- 8565590
TI  - The development of an ELISA method for the detection of "antibodies" to silicone.

PMID- 8565591
TI  - The adsorption of proteins on a polydimethylsiloxane elastomer (PEP) and their
      antigenic behavior.

PMID- 8565592
TI  - Aspecific immunoglobulin binding to hydrophobic surfaces.

PMID- 8565593
TI  - Cytotoxicity and membrane damage in vitro by inclusion complexes between gamma
      cyclodextrin and siloxanes.
AB  - Inclusion complexes of gamma-cyclodextrin and octamethylcyclotetrasiloxane (D4),
      decamethyltetrasiloxane (M10TS), and 1,3,5,7-tetramethyltetravinylcyclotetra -
      siloxane (TMTV-D4) were prepared to compare the cytotoxic effects of siloxanes in
      vitro. In these preparations, the hydrophobic siloxanes are surrounded by a
      hydrophilic shell of eight circularly linked D-glucose molecules (gamma
      cyclodextrin), and upon contact with plasma membranes the siloxane molecule can
      intercalate into the lipid bilayer of the cell membrane. XRPC24, 2-11
      plasmacytoma, CH12.LX lymphoma and P388D1 macrophage-like cells were used as
      indicator cells in toxicity assays. Using an MTT tetrazolium reduction to
      formazan test, a colorimetric method to determine the number of viable cells, the
      50% minimal lethal doses (CD50) for the siloxane compounds were found to range
      from 30 to 50 microM. Sublethal doses (e.g., 15 microM and lower) resulted in the
      loss of lactate dehydrogenase (LDH) and glutathione (GSH) from the cytosolic
      compartment of the target cells and thus indicated cytotoxicity. Treatment of
      macrophages with siloxanes resulted in a higher production of interleukin-6 (IL
      6) than was exhibited by untreated macrophages. The B9 cell bioassay of these
      treated cells showed as much as a 10 fold higher production (500 U/ml) of IL-6
      than did the untreated cells. The degree of increase was dependent on the
      compound and concentration used. The results of this study show that low
      molecular weight siloxanes produce lethal effects on B-lymphocyte derived target
      cells in vitro and permeabilize the plasma membranes at lower sublethal
      concentrations.

PMID- 8565594
TI  - The rubber mixes: allergic reactions to nonrubber products by testing with rubber
      mixes. Part I: The thiuram mix.

PMID- 8565595
TI  - Congenital and acquired early childhood syphilis.

PMID- 8565596
TI  - Acne vulgaris: tricks and treatments. Part I.

PMID- 8565597
TI  - Cutaneous side effects associated with interferon-alpha therapy: a review.
AB  - Interferon-alpha is a unique biological protein whose clinical use, both in
      dermatology and other fields of medicine, has greatly increased over the past
      several years. We present a review of the cutaneous side effects reported with
      the use of interferon-alpha.

PMID- 8565598
TI  - Cutaneous alternariosis in an immunocompromised patient.
AB  - A case of cutaneous alternariosis in a 68-year-old male farmer is presented. The
      patient had been treated with prednisone and azathioprine for thrombocytopenic
      purpura, and two months later he noted multiple ulcerated and slightly
      infiltrated granulomatous lesions on exposed areas. The diagnosis was confirmed
      by results of direct examination, culture of biopsy material, and histologic
      examination. A concurrent herpetic infection healed without sequelae. The
      protracted course of our patient's condition and a review of the literature
      suggest the tapering or stopping of steroids as the first step in the successful
      and permanent treatment of cutaneous alternariosis.

PMID- 8565599
TI  - Congenital subungual nevus in a black infant.
AB  - A 6-month-old black infant is described with a congenital black subungual and
      periungual lesion of the right second toe. Histopathologic examination revealed a
      junctional nevus. Congenital subungual nevi are rare. To the best of our
      knowledge, this represents the first report in a black infant.

PMID- 8565600
TI  - Botryomycosis in a patient with acquired immunodeficiency syndrome.
AB  - Botryomycosis is a bacterial infection of either the skin alone or in combination
      with visceral organs. It resembles a deep fungal infection. A histologic
      evaluation of cutaneous lesions reveals the characteristic Splendore-Hoepple
      phenomena and assists with management. Patients with acquired immunodeficiency
      syndrome (AIDS) tend to have uncharacteristic lesions resembling common
      conditions such as prurigo nodularis and lichen simplex chronicus. Diagnosis in
      these cases can be challenging. We report the case of a patient with AIDS who was
      successfully treated with Augmentin (amoxicillin, clavulanate potassium).
      Complete resolution of the lesion occurred after the causative agent,
      Staphylococcus aureus, was identified.

PMID- 8565601
TI  - Malignant melanoma.

PMID- 8565602
TI  - An unusual drug eruption to ampicillin.
AB  - The authors describe an unusual presentation of ampicillin allergy. A 24-year-old
      Chinese man noted localized pustular skin eruptions on his cheeks each time he
      ingested ampicillin. These eruptions would subside spontaneously within a week
      after stopping use of ampicillin. Drug provocation with ampicillin reproduced the
      same eruption in exactly the same sites. The eruptions were different clinically
      and histologically from fixed drug eruptions. The mechanism of such eruption is
      unknown.

PMID- 8565603
TI  - Marjolin's ulcer due to venous stasis.
AB  - The eponym Marjolin's ulcer is used to describe the malignant transformation of
      any benign ulcer or scar. The most common association is with burn scars, with
      the cancer occurring thirty years after the original injury. Venous stasis has
      been a rarely reported cause of this phenomenon. This case demonstrates such a
      finding, stressing the aggressive nature of these carcinomas, and therefore the
      need to examine a biopsy specimen when a benign ulcer presents with an atypical
      appearance.

PMID- 8565604
TI  - A pilot study of 5 percent permethrin cream versus 0.75 percent metronidazole gel
      in acne rosacea.
AB  - Acne rosacea is a common skin condition characterized by flushing episodes,
      erythema, telangiectasia, and recurrent crops of inflammatory papules and
      pustules that involve the face in a symmetrical distribution. A pilot study was
      conducted to compare topical 5 percent permethrin cream and 0.75 percent
      metronidazole gel in the treatment of acne rosacea. Six patients began treatment
      with 0.75 percent metronidazole gel twice daily to the right side of the face and
      permethrin 5 percent cream applied daily to the left side. Clinical evaluation
      was performed every two weeks. Five patients completed the study. The patients
      were treated for a range of seven to ten weeks. There were minimal adverse
      effects. Moderate improvement was seen on both sides.

PMID- 8565605
TI  - Pulse therapy with one-week itraconazole monthly for three or four months in the
      treatment of onychomycosis.
AB  - In an open study, twenty-eight patients with toenail onychomycosis were treated
      with monthly cycles of 400 mg itraconazole daily for one week for three (n = 5)
      or four (n = 23) consecutive months. In this patient sample, a total of seventy
      one toenails were affected, with a mean nail-plate involvement of 55 percent
      (range, 20 to 100 percent). Trichophyton rubrum was the most frequently isolated
      pathogen, followed by T. mentagrophytes. After active therapy, patients were
      evaluated for a maximum period of two years (mean, twelve months). A total of
      twenty-six of twenty-eight patients (93 percent) were considered as clinically
      cured. Of the remaining two patients, one was markedly improved and one appeared
      to have relapsed. Only three of seventy-one nails still exhibited some pathologic
      involvement. Of the twenty-six patients considered cured, mycologic examination
      at the final visit was performed on thirteen and the results were negative in all
      of them. The remaining clinically cured patients had no mycologic examination at
      the last visit. This short treatment was well tolerated; the only adverse
      reaction being a mild headache in one patient. Patients preferred this regimen to
      receiving daily treatment for three months. Pulse therapy consisting of monthly
      one-week cycles of 400 mg itraconazole daily for three to four months may offer a
      new option for treatment of onychomycosis. Further large-scale studies are
      required to confirm these findings.

PMID- 8565606
TI  - Caring for HIV-infected drug users: a provider's perspective.

PMID- 8565607
TI  - Allergic reactions to nonrubber products by testing with rubber mixes. Part III:
      The black rubber mix.

PMID- 8565608
TI  - Spider bite reactions.

PMID- 8565609
TI  - Acne vulgaris: tricks and treatments. Part II: The benzoyl peroxide saga.

PMID- 8565610
TI  - Unilateral Beau's lines associated with a fractured and immobilized wrist.
AB  - Beau's lines are transverse depressions of the nail plates. They are usually
      bilateral and result from a temporary cessation in the growth of the nail plate
      during severe systemic illnesses. Although transverse grooves can occur on the
      nails of one extremity, this has not been a commonly reported phenomenon. An
      unusual case of unilateral Beau's line associated with a metaphyseal fracture of
      the distal radius extending into the growth plate with wrist immobilization is
      presented. Other related causes of Beau's line are reviewed.

PMID- 8565611
TI  - Adenocarcinoma of the colon presenting with a Sister Mary Joseph's nodule and
      Trousseau's syndrome.
AB  - We describe an unusual case of colon cancer presenting with two dermatologic
      manifestations of internal malignancies: Trousseau's syndrome and Sister Mary
      Joseph's nodule. Trousseau's syndrome is associated with 1 to 11 percent of
      internal malignancies, while 5 percent of colorectal carcinomas present with
      cutaneous metastases. Our case highlights the clinical significance of
      dermatologic signs of occult gastrointestinal malignancies.

PMID- 8565612
TI  - Generalized pustular eruption associated with converting enzyme inhibitor
      therapy.
AB  - A 67-year-old man presented with a high fever and a generalized rash. His
      extended hospital stay was characterized by fever with repeated staphylococcal
      bacteremia and the appearance of axillary lymphadenopathy and splenomegaly. Skin
      lesions became hyperpigmented, dry, and atrophic with areas of exfoliation and
      uclers. Examination of skin and lymph node biopsy specimens showed findings
      consistent with mycosis fungoides. The patient unexpectedly recovered on
      discontinuation of captopril. A positive macrophage inhibiting factor response
      for both captopril and enalapril indicated that the non-sulfhydryl moiety was the
      antigenic stimulant for the lesion resembling mycosis fungoides.

PMID- 8565613
TI  - Bullous drug eruption to griseofulvin in a man with Hailey-Hailey disease.
AB  - Hailey-Hailey disease (chronic benign familial pemphigus) is a blistering disease
      characterized by episodic maceration and erosions in areas subject to friction
      and trauma such as the neck, axilla, and other intertriginous areas. We report a
      case in which a griseofulvin-induced drug eruption led to a generalized
      vesiculobullous eruption requiring treatment in a burn treatment center. This
      emphasizes that Hailey-Hailey disease, usually confined to relatively small
      areas, has the potential to cause blistering throughout the epidermis under
      certain conditions.

PMID- 8565614
TI  - A case of dermatofibrosarcoma protuberans on the right first toe.
AB  - Reports of dermatofibrosarcoma protuberans on a toe are extremely rare. It
      frequently occurs on the trunk and extremities. A Japanese woman presented with a
      dark-brownish hyperkeratotic plaque on the dorsal skin of her first toe. The
      initial clinical diagnosis of verruca vulgaris prompted treatment with
      cryotherapy. After that a glossy milky-white tumor appeared. Only the results of
      the histopathologic examination resulted in a diagnosis of dermatofibrosarcoma
      protuberans. The unusual macroscopic finding was considered to be due to
      repetitive stimulation by foot movement.

PMID- 8565615
TI  - Cutaneous Acanthamoeba infection in the acquired immunodeficiency syndrome:
      response to multidrug therapy.
AB  - Acanthamoeba, a free-living ameba of soil and water, produces the rare infections
      of granulomatous amebic encephalitis and amebic keratitis. We report a 38-year
      old white man with the acquired immunodeficiency syndrome (AIDS) who experienced
      Acanthamoeba infection that presented as multiple skin nodules without associated
      encephalitis. Histologic examination revealed necrotizing granulomatous
      inflammation with numerous amebic organisms that were cultured and identified as
      Acanthamoeba group 2, probably Acanthamoeba castellani by monoclonal antibodies.
      Results of in vitro susceptibility testing demonstrated resistance to all six
      tested drugs. A partial clinical response, however, was obtained with multidrug
      therapy.

PMID- 8565616
TI  - Flexural planar xanthomas: report of four cases.
AB  - Four patients with primary hyperlipoproteinemia, Frederickson's type IIb, were
      observed to have symmetrical planar xanthomas affecting flexures: finger webs,
      antecubital and popliteal fossae, axillae, and intergluteal cleft. Other types of
      xanthomas were also present and serum lipid electrophoresis showed type IIb
      pattern. We draw attention to the peculiar pattern of symmetrical planar
      xanthomatosis hitherto described only with type III disease and some forms of
      normolipemic xanthomatoses.

PMID- 8565617
TI  - Cutaneous Mycobacterium chelonei presenting in an immunocompetent host: case
      report and review of the literature.
AB  - Mycobacterium chelonei is in the family of fast-growing atypical mycobacteria.
      Clinical infection can have varying presentations. We present a case of a
      nonhealing thigh abscess that grew Mycobacterium chelonei on culture. The
      clinical presentations and causes of Mycobacterium chelonei infections are
      reviewed, along with current treatment options.

PMID- 8565618
TI  - Pustular vasculitis and superficial bullous pyoderma gangrenosum in a patient
      with ulcerative colitis.
AB  - A patient who showed a disseminated pustular eruption compatible with pustular
      vasculitis and concomitant bullous lesions with the features of superficial
      bullous pyoderma gangrenosum during an exacerbation of ulcerative colitis is
      described. These clinical findings could be an expression of a common
      immunopathogenic mechanism of inflammatory bowel disease and the neutrophilic
      dermatoses. It is suggested that pustular vasculitis is another skin
      manifestation of ulcerative colitis.

PMID- 8565619
TI  - Management of lacerations in sports: use of a biosynthetic dressing during
      competitive wrestling.
AB  - Lacerations occur commonly during competitive contact sports. Such injuries often
      limit the ability of the athlete to continue competition because of concerns
      about further trauma to the site and risks of infection. We describe herein the
      use of a biosynthetic dressing, Duoderm Thin, to protect lacerations received
      during competitive wrestling. The dressing was able to support the skin, protect
      the laceration from further injury, shield the wound from exposure to infectious
      agents, and prevent transmission of blood or serum to other wrestlers. Such
      protection enabled two wrestlers to continue competition and/or practice without
      adverse effects.

PMID- 8565620
TI  - Chromosomal variability and interracial hybridization in Drosophila bipectinata.
AB  - Three paracentric inversions, In(D)2L, In(C)2R and In(H)3L, often persist in
      laboratory stocks of Drosophila bipectinata initiated from flies collected from
      natural populations. In order to test the effect of interracial hybridization on
      the degree of chromosomal variability, four stocks of D. bipectinata originating
      from different geographical localities and which were polymorphic due to the
      presence of three inversions, were crossed with each other. Hybrid lines as well
      as parental lines which served as controls were maintained in food bottles for
      ten generations. After ten generations, chromosomal analysis of hybrid lines as
      well as parental lines was undertaken. The results revealed that: all hybrid and
      parental lines remained polymorphic; there was a decline in the frequency of
      heterozygous inversions in certain hybrid populations of mixed geographical
      origin; and there was variation with respect to the degree of chromosomal
      variability in different crosses involving different inversions. These results
      are discussed in the light of findings reported in other Drosophila species.

PMID- 8565621
TI  - The response to growth factors of cultured satellite cells derived from turkeys
      having different growth rates.
AB  - Satellite cells were isolated from the skeletal muscles of turkey varieties which
      grow at different rates to explore cellular mechanisms that may influence the
      rate of muscular growth. Satellite cells from the fast growing variety (Nicholas)
      were more responsive to insulin-like growth factors (IGFs) and insulin, and less
      responsive to fibroblast growth factor than were cells derived from the slow
      growing (Merriam's) turkey. IGF receptor affinities were similar between the
      Nicholas and Merriam's turkey satellite cells. The results suggest that
      differences in the responses of satellite cells to growth factors may influence
      rates of skeletal muscle accretion and whole body growth.

PMID- 8565622
TI  - Optimal preservation of the J1-31 antigen in astroglia examined by immunogold
      labelling.
AB  - Several methods for the detection of immunogold labelling for the monoclonal
      antibody (Mab) J1-31 in astroglial cells are described. The optimal preservation
      of the gold labelling is achieved in sections after cryoultramicrotomy or LR
      white embedding. The results obtained are consistent with the previous findings
      that the Mab J1-31 antigen is an intermediate filament-associated protein in the
      astroglial cells.

PMID- 8565623
TI  - The pathogenic role of the coccoid form of Helicobacter pylori.
AB  - Adherence of the coccoid forms of Helicobacter pylori to the gastric carcinoma
      cell line (KATO III) was examined by transmission electron microscopy.
      Specialized attachment sites such as the 'adhesion pedestal', 'cup-like
      indentation' and 'abutting adhesion' were seen in the interaction between
      coccoids and epithelial cells. These adherence patterns were similar to those
      observed with spiral forms in gastric biopsy specimens in vivo, suggesting a
      possible pathogenic role for the coccoids of H. pylori. With antigens prepared
      from both the coccoid and spiral forms, IgG antibodies reactive to H. pylori were
      detected using ELISA. Patients with gastroduodenal disease accounted for 74%
      (37/50) ELISA positives. Of the 50 healthy blood donors, 32 and 28% were
      seroreactive to coccoid and spiral antigens, respectively. These sera were
      further characterized by Western blot where immunoreactive protein bands of 128,
      116, 110, 95, 91, 66, 60, 54, 50 and 33 kD were conserved in both the coccoid and
      spiral forms. These findings suggest that the coccoids could be a differentiated
      infective form of H. pylori, and that they could evoke an immune response from
      the host after invading the cells via specialized attachment sites.

PMID- 8565624
TI  - Rat 5S rDNA spacer sequences and chromosomal assignment of the genes to the
      extreme terminal region of chromosome 19.
AB  - Fragments of the spacer region of genes for rat 5S ribosomal RNA (rDNA), which
      are tandemly repeated, were amplified by PCR with primers specific to the two
      ends of the coding region for 5S rRNA. Two amplified fragments of approximately
      1.6 kb were subcloned and sequenced. The spacer sequences showed a high degree of
      sequence identity to each other (99.2%) but substantial divergence from those of
      analogous mouse clones. The homologous regions in the mouse clones were
      interrupted by the duplication or deletion of small segments of DNA. A 12-mer, 5'
      GGCTCTTGGGGC-3', thought to be responsible for efficient transcription, was
      located from position -33 to position -22 in the rat -5S clones. The genes were
      mapped by fluorescence in situ hybridization with cloned fragments of rat 5S rDNA
      as probe. The genes were localized exclusively in a single telomeric region of
      chromosome 19.

PMID- 8565625
TI  - Suppression of Lck protooncogene expression in murine somatic cell hybrids
      between T lymphoma cells and fibroblasts.
AB  - Somatic cell hybrids were obtained by cell fusions between Lck-positive EL4 mouse
      T lymphoma cells and Lck-negative B82 mouse fibroblasts of S194 mouse
      plasmacytoma cells to examine negative control of lck gene expression in the
      resulting hybrids. Western blot analysis using a monoclonal antibody against the
      Lck protein showed a marked decrease in p56lck expression in B82 x EL4 (BEL)
      hybrids. In contrast to BEL hybrids, the level of p56lck was not changed
      significantly in S194 x EL4 (SEL) hybrids and was approximately one-half of that
      seen in EL4 cells. Diminished expression of the Lck protein in BEL hybrids
      paralleled downregulation of lck mRNA, which was exclusively transcribed from the
      distal promoter in EL4 cells. It is unlikely that the suppression was simply a
      consequence of chromosome segregation critical for lck gene expression, since BEL
      hybrids retained the EL4-derived lck gene and most of the chromosomes from both
      parental cells. The results from treatment of BEL hybrids with actinomycin D or
      cycloheximide suggested that suppression of lck gene expression in the hybrids
      might not be due to posttranscriptional control. DNA methylation status in the
      lck distal promoter and the coding regions did not appear to correlate with the
      expression of the gene. Our results suggest that negative control of lck gene
      expression differs between fibroblasts and B cells, in that lck gene expression
      in T cells can be shut down by transfer of a putative repressor factor or factors
      in fibroblasts but not in B cells.

PMID- 8565626
TI  - Microsatellite mapping of the deletion in patients with hereditary neuropathy
      with liability to pressure palsies (HNPP): new molecular tools for the study of
      the region 17p12 --> p11 and for diagnosis.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal
      dominant peripheral neuropathy characterized by recurrent episodes of nerve
      palsies. We have analyzed 11 microsatellite markers from chromosome 17p12 --> p11
      in nine French families with HNPP. The three microsatellites D17S839
      (afm200yb12), D17S955 (afm317ygl), and D17S921 (afm191xh12) were localized in the
      deleted region. In allele segregation analyses, the microsatellite D17S793
      (afm165zd4) detected two chromosome 17-linked loci, one of which was deleted in
      HNPP patients. Using these STR markers, we found that the deletion coincided with
      the CMT1A/HNPP monomer unit in eight of the nine families. In the remaining
      pedigree, the deletion lay between the centromeric microsatellite D17S805
      (afm234tal) and the telomeric marker D17S922 (afm197xh6), which flank the CMT1A
      monomer unit. Comparison of these data with the available genetic and physical
      maps of 17p12 --> p11 shows that this region, which is frequently subject to
      rearrangement-inducing diseases, such as Smith-Magenis syndrome, Charcot-Marie
      Tooth type 1A, and HNPP, presents recombination hot spots. Finally, this study
      demonstrates the usefulness of the D17S122 (RM11GT) and D17S921 (afm191xh12)
      microsatellites as tools for the molecular diagnosis of HNPP.

PMID- 8565627
TI  - Karyotypic patterns of seven species of molossid bats (Molossidae, Chiroptera)
AB  - G- and C-banding patterns of seven species of the bat family Molossidae, Eumops
      glaucinus, E. perotis, Molossops abrasus, M. temminckii, Molossus ater, M.
      molossus, and Nyctinomops laticaudatus, were identified. Comparisons among the
      karyotypes of these species showed extensive homologies between E. perotis, M.
      ater, M. molossus, M. abrasus, and N. laticaudatus, demonstrating inter- and
      intrageneric conservatism, and a lesser degree of homologies in M. temminckii and
      E. glaucinus, reflecting intrageneric variation. Chromosomal variation was due to
      inversions, Robertsonian rearrangements, translocations, and variations in the
      location of constitutive heterochromatin and nucleolus organizer regions. The
      chromosome corresponding to No. 5 in the M. ater karyotype is discussed. We
      suggest that the Nyctinomops and Molossops karyotypes represent the primitive
      condition and that Molossus and Eumops have derived karyotypes.

PMID- 8565628
TI  - FISH and PRINS, a strategy for rapid chromosome screening: application to the
      assessment of aneuploidy in human sperm.
AB  - The co-utilization of FISH and PRINS techniques for in situ chromosome screening
      was tested on human sperm nuclei. We used a centromeric repeat probe specific for
      chromosome 4 for FISH. PRINS reactions were performed with alpha-satellite
      primers specific for either chromosomes 9 or chromosome 18. Double labeling was
      obtained and estimates of disomy rates were carried out for the three
      chromosomes.

PMID- 8565629
TI  - Physical mapping of SOD1 to bovine chromosome 1.
AB  - Superoxide dismutase 1 (SOD1) was mapped to cattle chromosome 1q12 --> q14 by in
      situ methods. Both traditional in situ hybridization using tritium and a new
      technique, direct in-situ single copy PCR (DISC-PCR), were used in two separate
      laboratories. Both human and bovine SOD1 clones were tritium labeled for
      radioactive in situ hybridization. A primer pair based on the bovine SOD1 gene
      (Barendse et al., 1994b) was used for the DISC-PCR procedure. The map location of
      SOD1 is close to collagen 6A1. SOD1 is a potentially important type 1 anchor
      locus in the region where the gene for horns in cattle was recently mapped
      (Georges et al., 1993; Schmutz et al., 1995).

PMID- 8565630
TI  - Human endogenous retroviral element k10 (HERV-K10): chromosomal localization by
      somatic hybrid mapping and fluorescence in situ hybridization.
AB  - The human endogenous retrovirus K10 (HERV-K10) was mapped to human chromosomes
      using HERV-K10 specific PCR primers on a somatic hybrid mapping panel. A non
      random chromosomal location was demonstrated with PCR signals on chromosomes 1,
      3, 4, 5, 6, 7, 10, 11, 12, 14, 15, 19, 20, 21, 22 and Y. There was a lack of PCR
      products on the other chromosomes, even after hybridization with a HERV-K10
      specific probe. To further localize the HERV-K10 sequence we used fluorescence in
      situ hybridization. Chromosomes 1, 3, 6, 7, 10, 11, 12 and 22 were found to
      contain several HERV-K10 sequences in different regions. The presence of several
      integration sites on some chromosomes is consistent with previous studies
      demonstrating 30-50 copies of the HERV-K10 sequence per haploid genome. The
      mapping information reported in this study will assist the analysis of the
      biological significance of the HERV-K10 sequence.

PMID- 8565631
TI  - Case report: unusually high rates of aneuploid embryos in a 28-year old woman
      with incontinentia pigmenti.
AB  - A young female carrier for incontinentia pigmenti underwent preimplantation
      genetic diagnosis to prevent the transfer of affected embryos. FISH diagnosis was
      performed using X, Y, 18 and 13/21 probes. Unexpectedly, 57% of the embryos were
      aneuploid for these chromosomes, a rate significantly higher (P < 0.005) than
      expected (9.3%). The patient achieved pregnancy but spontaneously aborted a
      trisomy 9 fetus.

PMID- 8565632
TI  - Cytogenetic effects of advanced maternal age and delayed fertilization on first
      cleavage mouse embryos.
AB  - It has been shown that both advanced maternal age and delayed fertilization may
      induce chromosomal anomalies. We therefore examined the combined effects of these
      two factors on chromosomal anomalies in first-cleavage mouse embryos. We set up
      normal and (6-h) delayed subgroups in two different age groups (young, 3-4 mo;
      aged, 9-11 mo) and compared the incidence of chromosomal anomalies. In first
      cleavage embryos, egg-derived chromosomes can be distinguished from sperm-derived
      chromosomes. The incidence of maternally derived aneuploidy was highest in the
      aged-delayed fertilization subgroup. We therefore conclude that advanced maternal
      age affects the production of aneuploidy more severely when combined with the
      effect of delayed fertilization.

PMID- 8565634
TI  - Demonstration of homoeologies between human and lemur chromosomes by chromosome
      painting.
AB  - Human-specific probes for chromosomes 3, 7, 9, 14, 19, and 21 were used to paint
      chromosomes of three lemur species: Eulemur fulvus mayottensis, E. macaco macaco,
      and Lemur catta. Chromosomes 1 and 3 of E. f. mayottensis are homoeologous to
      human chromosomes 3, 9, 14, and 21, as previously suggested by chromosome
      banding. Probes for human chromosomes 7 and 19 produced unexpectedly strong
      signals in the centromeric regions of all lemur chromosomes, suggesting that
      sequences homologous to nonrepeated sequences of the human genome have been
      amplified during the formation of constitutive heterochromatin in lemurs.

PMID- 8565633
TI  - Detection of triplet repeat sequences in yeast artificial chromosomes using
      oligonucleotide probes: application to the SCA1 region in 6p23.
AB  - In this paper, we describe labeling and hybridization conditions for
      oligonucleotide probes that detect human triplet repeat sequences in yeast
      artificial chromosomes (YACs). Restriction digests of YACs containing the CAG
      repeat sequence of the SCA1 gene were used as positive controls. Several
      hybridization mixtures and temperatures and two different labeling techniques
      were tested in order to determine optimal conditions. CAG, CGG, AGG, and ATT
      repeat sequences were mapped on YACs from a contig in 6p23, where SCA1 is
      located.

PMID- 8565635
TI  - Localization by fluorescence in situ hybridization of the human functional beta
      glucuronidase gene (GUSB) to 7q11.21 --> q11.22 and two pseudogenes to 5p13 and
      5q13.
AB  - The gene coding for human beta-glucuronidase (GUSB) was mapped to 7q11.21 -->
      q11.22 by fluorescence in situ hybridization (FISH), thus clarifying the
      contradictory published localizations of this gene. Multiple unprocessed
      pseudogenes and pseudogene fragments for GUSB have been described. However, only
      two weak signals, one at chromosome band 5p13 and the other at 5q13, could be
      detected with FISH, suggesting considerable divergence between GUSB and its
      related sequences.

PMID- 8565636
TI  - Sperm segregants from the murine Rb(11.14) heterozygote fertilizing in vivo and
      in vitro.
AB  - Segregants of the Rb(11.14) translocation in 17 heterozygous male mice were
      analyzed in G- and C-banded first-cleavage metaphases after in vivo (n = 440) and
      in vitro (n = 267) fertilization. Mating intervals of 3 and 14 d provided unaged
      and physiologically aged sperm for the oocytes, which were from chromosomally
      normal females. Significantly more normal than balanced sperm segregants were
      seen in both the in vivo fertilized (P < 0.01) and in vitro fertilized (P <
      0.001) study groups. The distortion was elevated in vitro (P < 0.02),
      unaccompanied by a sex-ratio distortion, and had a segregant distribution that
      was independent of sperm age; thus it differs from that seen for other
      translocations. The findings argue for chromosome-specific effects of
      Robertsonian translocations on sperm function. A significantly (P < 0.05)
      increased hyperhaploidy rate (unrelated to the translocation) supports the sperm
      aging hypothesis.

PMID- 8565637
TI  - Assignment of the gene for beta-casein (CSN2) to 4q13 --> q21 in humans and 3p13 
      -> p12 in chimpanzees.
AB  - The human beta-casein gene (CSN2) has been mapped by fluorescence in situ
      hybridization to human chromosome 4q13 --> q21 and to the homologous chimpanzee
      chromosome at 3p13 --> p12. This confirms the presence of a pericentric inversion
      that distinguishes the two species, as first observed by chromosomal banding
      studies.

PMID- 8565638
TI  - A 3.1-Mb YAC contig within the Werner syndrome region, on the short arm of human
      chromosome 8.
AB  - The locus for Werner syndrome (WRN) has been localized to human chromosome 8p21 -
      > p12, close to the anonymous marker D8S339. A 3.1-Mb contig of yeast artificial
      chromosomes (YACs) was assembled around D8S339. Results from analyses of somatic
      cell hybrids, FISH, and physical mapping suggest the following loci order: tel
      NEFL-D8S131-D8S339-[D8S540/GSR]-D8S124 -D8S259-D8S87-FGFR1-cen. Close physical
      linkage between D8S540 and GSR was established within a DNA fragment of 200 kb.
      These two loci are not more than 400 kb from D8S339. In addition, D8S339, D8S540,
      D8S124, and GSR are within 1.1 Mb. These data establish a primary physical map of
      the Werner syndrome region and identify useful YAC clones for the isolation of
      new markers and of the corresponding gene.

PMID- 8565639
TI  - A 19-allele polymorphic marker within the centromere of human chromosome 5.
AB  - We have detected and characterized a highly polymorphic marker that maps to the
      centromere of human chromosome 5. The localization was established by both
      linkage analysis within the CEPH reference families and fluorescence in situ
      hybridization. The marker consists of a sequence of five nucleotides, (CCTTT)n.
      Nineteen alleles have been detected in 46 unrelated individuals from 12 CEPH
      families, with a calculated heterozygosity of 0.91. This is the first truly
      centromeric, highly polymorphic genetic marker described so far.

PMID- 8565640
TI  - Regional assignment of EST sequences on human chromosome 13.
AB  - We have used a panel of somatic cell hybrids carrying structural rearrangements
      of human chromosome 13 to regionally localise 10 expressed sequence tags (ESTs)
      from this chromosome. Three of these genes were not present in the somatic cell
      hybrid PGME, which contains chromosome 13 as its major human component. Using a
      panel of somatic cell hybrids, two of these genes were localised to chromosome 8
      and one to chromosome 16. Using the PCR primers as published, it was impossible
      to map one EST; consequently, a YAC containing this gene was isolated, and
      fluorescence in situ hybridisation was used to map the gene to 13q14. The
      distribution of the remaining six chromosome 13-specific ESTs was nonrandom; one
      mapped to 13q14 and the remaining five to 13q12, with three mapping within the
      proximal portion and two mapping within the distal portion of this region.

PMID- 8565641
TI  - The human homologue of the murine Llglh gene (LLGL) maps within the Smith-Magenis
      syndrome region in 17p11.2.
AB  - We have isolated and characterized the human homologue of the murine Llglh gene,
      which was originally isolated as a homologue of a Drosophila tumor suppressor
      gene 1(2)gl (lethal(2) giant larvae). In the mouse, Llglh is thought to play an
      important role during brain development as a regulatory target of Hoxc8. The
      human homologue of Llglh (LLGL) encodes a protein consisting of 1,033 amino
      acids. This gene was mapped by fluorescence in situ hybridization (FISH) to human
      chromosome 17p11.2, a region that is typically deleted in patients with Smith
      Magenis syndrome (SMS). In our FISH analysis of metaphase chromosomes of four SMS
      patients, a probe representing LLGL failed in each case to hybridize to one of
      the two chromosome 17 homologues, indicating that this gene may play a role in
      the pathogenesis of SMS.

PMID- 8565642
TI  - The rat genes encoding the pancreatitis-associated proteins I, II and III (Pap1,
      Pap2, Pap3), and the lithostathin/pancreatic stone protein/regeneration protein
      (Reg) colocalize at 4q33-->q34.
AB  - Using fluorescence in situ hybridization, we determined that the three rat PAP
      genes, and the related REG gene map in the same chromosomes region, namely 4q33-
      >q34. This rat chromosome region is thus homologous to the human 2p12 region,
      which also contains the PAP gene, the REG1A gene, and a REG-related gene (REGL).

PMID- 8565643
TI  - Cloning, expression, and mapping of UBE2I, a novel gene encoding a human
      homologue of yeast ubiquitin-conjugating enzymes which are critical for
      regulating the cell cycle.
AB  - From a human fetal-brain cDNA library we isolated a novel gene sharing
      significant homology with two yeast genes, UBC9 and hus5, which encode ubiquitin
      conjugating enzyme 9 (UBC9). In yeast this protein is critical for normal
      mitosis, and seems to be closely involved in progression of G2 to M phase of the
      cell cycle. The human UBC9 (h-UBC9) cDNA, (gene symbol UBE2I), contained an open
      reading frame of 474 nucleotides encoding 158 amino acids. Its predicted peptide
      showed respectively 56% and 66% identity (75% and 82% similarity) with the
      products of UBC9 and hus5. Northern-blot analysis revealed expression of three
      transcripts, 6.4 kb, 3.3 kb, and 1.35 kb, in all human tissues examined. This
      gene, UBE2I, was mapped to chromosome band 16p13.3 by FISH.

PMID- 8565644
TI  - Comparative RB1 gene mapping in Homo sapiens, Pithecia pithecia, Macaca sylvana,
      and Cercopithecus aethiops tantalus.
AB  - The chromosomal localization of the gene for retinoblastoma (RB1), which has been
      mapped to band 13q14 in man, was studied by in situ hybridization on metaphase
      chromosomes of selected primates, including Pithecia pithecia, Macaca sylvana,
      and Cercopithecus aethiops tantalus. The results allowed us to determine the
      position of the bands homologous to human chromosome band 13q14 in these species.
      Hybridization analysis corroborated the results of previous studies that defined
      the chromosome homologous to human chromosome 13 (HSA 13) in these species. By
      comparing RB1 localizations and banding patterns, it is shown that the
      rearrangement separating HSA 13 from its homologous chromosome in Cercopithecidae
      is not a pericentric inversion, as suggested by earlier studies. Since the
      banding pattern and RB1 localization are not changed, the modification of the
      centromeric index is explained by a centromeric shift or by two inversions, one
      pericentric and one paracentric.

PMID- 8565645
TI  - Mapping 638 STSs to regions of human chromosome 3.
AB  - The initial step of mapping STSs to chromosome 3 has been by mapping to a
      reference panel of 21 somatic cell hybrids containing fragments of chromosome 3.
      In this study we map 638 STSs to 23 bins on chromosome 3. The bin information
      greatly facilitates further mapping by radiation hybrids and YAC clones.

PMID- 8565646
TI  - The detection of contiguous gene deletions at the neurofibromatosis 1 locus with
      fluorescence in situ hybridization.
AB  - Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized
      primarily by the development of multiple neurofibromas and pigmentary changes.
      The recent identification of contiguous gene deletions in NF1, a previously
      unrecognized molecular basis for this disorder, raises important questions
      regarding deletion frequency in the patient population and the role that
      contiguous genes may play in the physical manifestations of NF1 patients. To
      facilitate the identification of patients with large NF1 deletions, we have
      isolated clones carrying large genomic segments from the NF1 locus and tested
      their efficacy as probes for fluorescence in situ hybridization (FISH). Clone P1
      9 spans approximately 65 kb of the NF1 gene, including exons 2-11, and clone P1
      12 carries approximately 55 kb of NF1 intron 27B. FISH studies performed with P1
      9, P1-12, and a set of overlapping 1F10 cosmid clones mapping telomeric to the
      NF1 locus identified large deletions in two new neurofibromatosis type 1 patients
      who, like previously characterized deletion patients, had mildly dysmorphic
      facial features and large numbers of cutaneous neurofibromas.

PMID- 8565647
TI  - A comparison of children's behaviors following three types of stressors.
AB  - One purpose of this study was to examine the differences in behavior of children
      exposed to trauma versus no trauma. Another goal was to compare different types
      of traumatic events in terms of their effects on behaviors. Our analysis
      indicated significant differences between trauma and no trauma groups. Additional
      analyses indicated that those children who were allegedly sexually abused were
      rated as exhibiting higher levels of symptomatology on all three factors of the
      Pediatric Emotional Distress Scale (PEDS) as well as the Total PEDS score than
      the other three groups.

PMID- 8565648
TI  - A training guideline of cultural competence for child and adolescent psychiatric
      residencies.
AB  - The author proposes a curriculum guideline of cultural competence for child and
      adolescent psychiatric residencies, including specific educational objectives,
      didactic topics and suggested references. These guidelines can be easily
      incorporated into the existing training curriculum and stress ethnogeneric and
      developmental perspectives, which can be expanded further to include
      ethnospecific issues depending on the needs of each training program and trainee.

PMID- 8565649
TI  - Psychopathology in the families of inpatient affective disordered adolescents.
AB  - The purpose of this study was to examine the rates of psychiatric disorders in
      the parents of affective disordered adolescent inpatients, and to examine
      characteristics of the adolescent patients' illnesses and hospital stays for
      effects of having a concurrently depressed mother. Twenty-three percent of the
      depressed probands (N = 33), 20% of the bipolar group (N = 10), and 9% of the
      psychiatric control group (N = 11) had mothers who reported major depression (MD)
      at the time of hospitalization. Concurrent maternal depression did not have
      prominent effects on the course of the adolescents' hospitalizations.

PMID- 8565650
TI  - Parent and teacher reports of problem behaviors in child psychiatric inpatients:
      cross-informant correlations on admission and at 5-month follow-up.
AB  - The present study compared parent and teacher evaluations of behavioral problems
      in a sample of school-age child psychiatric inpatients on admission and at 5
      month follow-up. Both parents and teachers viewed changes in children's
      emotional/behavioral problems over the course of the follow-up period rather
      similarly. In general, parents and teachers viewed children's behavior as
      significantly improved relative to pretreatment.

PMID- 8565651
TI  - Developmental and symptom specificity of hopelessness, cognitive errors, and
      attributional bias among clinic-referred youth.
AB  - The present study examined the unique and interactive relationships between age
      and indices of psychopathology (i.e., anxiety, aggression, and depression), with
      three types of maladaptive cognitions: hopelessness, negative cognitive errors,
      and attributional bias. Some negative cognitions were not unique to depression
      and were associated with broader psychopathology. Developmental considerations
      also influenced some negative cognitions or qualified the association between
      negative cognitions and depression.

PMID- 8565652
TI  - Prenatally drug-exposed children in out-of-home care: are we looking at the whole
      picture?
AB  - Publicity on children exposed prenatally to drugs has fostered tremendous concern
      about their cognitive and behavioral development. This concern is reflected in
      the out-of-home care system, where the number of children from drug-involved
      families has increased dramatically. This article examines the conflicting views
      in the literature on the effects of prenatal exposure to drugs and reports on an
      early intervention project in a New York City agency. The rate of developmental
      delay was found to be virtually the same for children with and without prenatal
      exposure to drugs. Implications of these findings for practice and research are
      considered.

PMID- 8565653
TI  - Statistical information of the development of China's health work in 1994. Report
      from the Information Centre of Health Statistics of the Ministry of Public Health
      of China.

PMID- 8565654
TI  - Neurosurgery in China.

PMID- 8565655
TI  - Recent progress in the study of anticancer drugs originating from plants and
      traditional medicine in China.

PMID- 8565656
TI  - Taking the path of combining traditional Chinese medicine with Western medicine
      in cancer research and control.

PMID- 8565657
TI  - Guillain-Barre syndrome in six cities and provinces of northern China: is it a
      new entity?
AB  - Forty cases of Guillain-Barre Syndrome were reported, (GBS) which came from the
      regions where "Chinese Paralytic Syndrome" and "Acute Motor Axonal Neuropathy
      (AMAN)" were presented before. A study on their clinical, electrophysiological
      and pathological features was conducted, records on 3,733 GBS cases reported in
      northern China from 1978 to 1992 were reviewed and compared with cases of "acute
      moter axonal nouropathy". The results showed that the clinical,
      electrophysiological and pathological features of GBS in north China are similar
      to those of typical GBS cases in western countries, though there seemed to be
      some special epidemiological features in age, seasonal and regional distribution.
      It was concluded that the GBS in northern China is demyelinating GBS dominantly,
      not a new entity.

PMID- 8565658
TI  - Distribution of an NcoI polymorphism in the lymphotoxin alpha gene in Dutch
      patients with inflamatory bowel diseases.
AB  - An NcoI restriction fragment length polymorphism in the first intron of the
      lymphotoxin alpha gene was investigated in 35 patients with Crohn's disease, 40
      patients with ulcerative colitis, and 30 unrelated healthy controls, all of Dutch
      origin. The results showed that no significant differences existed in the
      genotype frequencies of the NcoI polymorphism in the first intron of the LT alpha
      gene between ulcerative colitis patients or Crohn's disease patients and the
      healthy controls. The study indicates that the NcoI polymorphism in the LT alpha
      gene can not be used as a genetic marker for the predisposition to inflammatory
      bowel diseases. However, since this polymorphism may control the production of
      tumor necrosis factor, study of this and other related tumor necrosis factor gene
      polymorphisms may be used as markers to identify patient subgroups and to define
      patient heterogeneity. Further studies are being carried out on other
      polymorphisms and on the relevance of LT alpha and TNF alpha haplotypes.

PMID- 8565659
TI  - Relationship between coronary angioscopic and intravascular ultrasound imaging
      and restenosis.
AB  - In order to investigate the relationship between restenosis and the morphology
      detected by coronary angioscopy (CASC) and introvascular ultrasound imaging
      (IVUS), 17 patients were detected by CASC and IVUS immediately and 3 months after
      percutaneous transluminal coronary angioscopy (PTCA). The results showed that the
      dilation index by IVUS (DIu) was significantly lower in restenosis patients than
      in non-restenosis patients (0.42 +/- 0.08 versus 0.78 +/- 0.16, P < 0.01) and
      that the elastic recoil (ER) was higher in restenosis patients than in non
      restenosis patients (4.51 +/- 1.42 mm2 versus 1.63 +/- 1.20 mm2, P < 0.01), and
      that the elastic recoil rate (ERR) was also higher in restenosis patients than in
      non-restenosis patients (57.3 +/- 8.07% versus 21.80 +/- 16.84% P < 0.01), and
      that coronary dissection, atheromatous plaque and calcification as well as the
      colour of inner coronary artery had no relation with chronic restenosis. In
      conclusion, the elastic recoil is one of the important factors of chronic
      restenosis after PTCA.

PMID- 8565660
TI  - Biomedical material for sutureless esophagogastrostomy. Analysis of 31 cases.
AB  - The results of 31 cases of sutureless esophagogastrostomy by intraluminal elastic
      circular ligation (IECL) with the biodegradable supporting tube were reported.
      The fate of the supporting tube could be tracked satisfactorily by X-ray. The
      tube-dislodge time was 15.03 +/- 2.23 days and unaffected by the size of
      supporting tube or the site of anastomosis. The supporting tube could be safely
      absorbed or partially discharged through the alimentary tract. IECL, with the
      merits of saving time, anastomosing tightly and leaving no suture materials in
      the anastomotic site, can be expected to further reduce the incidence of
      anastomotic leakage and provide references for other gastrointestinal
      anastomosis.

PMID- 8565661
TI  - Superficial carcinomas of the esophagus and gastric cardia. A clinicopathological
      analysis of 141 cases.
AB  - From January 1970 to June 1992, 141 patients with superficial esophageal and
      cardiac carcinomas (SEC and SCC) underwent surgical treatment. Of the 141
      patients 128(90.8%) had slight symptoms related to swallowing, and the remaining
      13(9.2%) were asymptomatic. Balloon cytology and esophagoscopy proved very useful
      for the diagnosis of SEC and SCC, and Lugol's solution staining technique was an
      effective auxiliary diagnostic measure. Lymph node metastasis was not found in
      patients with epithelial (EP) cancer. However, it was present in one (2.9%) of 34
      patients with muscularis mucosal (MM) invasion, and in 5 (8.6%) of 58 patients
      with submucosal (SM) cancer. The 5-year survival rates of the patients with SEC
      and SCC were 75.5% and 71.4%, respectively (P > 0.05). The different depth of
      tumor invasion including EP, MM and SM cancers showed significant differences in
      the 5-year survival rate (P < 0.05). Although the prognosis for the patients with
      lymph node metastasis is poor, we should advocate extended lymph node dissection
      in surgical treatment of the patients in whom MM and SM cancers are suspected.

PMID- 8565662
TI  - DNA content and morphological parameters in synovial sarcoma and synovioma.
AB  - By using image analysis technique with 6 normal synovial tissue specimens as
      controls, nuclear DNA content and morphological parameters in specimens from 51
      synovial sarcomas and 15 synovioma were examined quantitatively. The DNA content
      in synovial sarcoma and synovioma was significantly different (P < 0.01), and
      that of synovioma and normal synovial tissue was also different (P < 0.05).
      Morphological parameters including nuclear areas and perimeters differed
      significantly among the above three groups (P < 0.01). There was no correlation
      between the DNA content of synovial sarcoma and its histologic type (P > 0.05),
      but the DNA content greatly differed between its higher and lower differentiated
      grade in each type (P < 0.01). The DNA content in synovial sarcoma IIA stage,
      according to Enneking's staging system was lower than that in IIB, IIIA and IIIB
      (P < 0.05). The 5-year survival rate of synovial sarcoma with diploid/nearly
      diploid (D/ND) pattern was higher than that of aneuploid (AN) pattern (P =
      0.028). The study suggests that analysis of the DNA content and morphological
      parameters of tumor cells is helpful in the diagnosis and pathologic grading of
      synovial sarcoma. It also provides a guide to clinical operation and estimation
      of the prognosis. Although synovioma is usually a well-differentiated and benign
      lesion, this investigation also suggested that increased DNA content may be an
      indication of poor prognosis for this neoplasm.

PMID- 8565663
TI  - Clinical application of monoclonal antibody-drug conjugate to immunotargeting
      chemotherapy of bladder cancer.
AB  - Monoclonal antibody-drug conjugate was applied in a clinical trial for patients
      with bladder cancer. Monoclonal antibody HB7A from a mouse splenocyte immunized
      against human bladder cancer was used as a drug carrier. The anti-cancer drug
      adriamycin (ADR) was bound to HB7A through a dextran (DEX) bridge to form the
      conjugate HB7A-DEX-ADR. The in vitro cytotoxic effect of the conjugate on BIU-87
      bladder cancer cells was similar to that of free ADR and the mixture of HB7A and
      ADR. Seven patients with bladder cancer were given HB7A-DEX-ADR intravenously.
      The immunoperoxidase studies of the resected specimens showed that HB7A was
      localized specifically in cancer, and histological studies revealed degenerative
      and necrotic changes of the tumor cells. Patients receiving the conjugate did not
      experience serious side effects. This study suggests that immunotargeting
      chemotherapy with HB7A-DEX-ADR is well tolerated by patients and its cytotoxicity
      on tumor is substantial.

PMID- 8565664
TI  - Evaluation of a tubular mesh and a spiral stent woven from titanium nickel alloy
      for prostatic obstruction in patients at high risk for surgery. Report of 62
      cases.
AB  - The use of two urethral stents woven from titanium nickel alloy (TiNi) in the
      form of a tubular mesh or a spiral stent (both made in China) is described. They
      were implanted in 62 patients with prostatic outflow obstruction. All patients
      were considered contraindicated for surgery. They were divided into a spiral
      stent group (group 1) treated between March 1992 and May 1993, comprising 35
      cases, and a tubular mesh group (group 2) treated between October 1993 and
      December 1994, comprising 31 cases, including four failures in group 1. Thirty
      three out of the 35 patients in group 1 were treated successfully. Good results
      were achieved in eight cases (22.8%) and significant improvements occurred in 24
      (68.5%), giving a total effective rate of 91.3%, with a follow-up of 11 to 27
      months. Fourteen stents were removed within 6 months after the insertion and six
      more were removed within 12 months. The mean effective time of the stent in situ
      was 10.8 months. All 31 cases in the mesh group were treated successfully.
      Dramatically good effects were obtained in 28 cases (over 90%) and distinct
      improvements were achieved in two, giving a total effective rate of over 96.5%,
      with a follow-up of 6 to 14 months (mean 10.5 months). Cystoscopy was carried out
      in 12 patients after 6 months following the insertion. The major part of the
      meshes became covered by urothelium. Compared with the spiral, the mesh makes it
      possible to insert a prosthesis with a larger diameter and anti-pressure. The
      spiral, however, can be used as a temporary alternative for the relief of
      prostatic obstruction. A tubular mesh can work well for the relief of prostatic
      obstruction and remain in situ without causing major problems for at least 1
      year.

PMID- 8565665
TI  - Proceedings of the Third International Meeting of Tropical Medicine and
      Parasitology, Kunming, Yunnan Province, China.

PMID- 8565666
TI  - Preliminary report on the results of nutrition prevention trials of cancer and
      other common diseases among residents in Linxian, China.

PMID- 8565667
TI  - Studies on adrenomedullin: a novel hypotensive peptide.

PMID- 8565668
TI  - The effect of low dose aspirin on the platelet function in patients with acute
      myocardial infarction (AMI).

PMID- 8565669
TI  - Alterations of the percentage of lymphocytes in patients with acute myocardial
      infarction and clinical evaluation.

PMID- 8565670
TI  - Epidemiological study of primary Sjogrne's syndrome in China.

PMID- 8565671
TI  - Alzheimer's disease survey in Guangdong of China.

PMID- 8565672
TI  - Caroli's disease: report of 40 cases.

PMID- 8565673
TI  - Pregnancy achieved after treatment in a case of endometrial ossification. A case
      report and literature review.

PMID- 8565674
TI  - Pancytopenia after repeated radioiodine treatment on metastatic thyroid cancer to
      bone.

PMID- 8565675
TI  - Heterotopic ossification in adenocarcinoma of the colon.

PMID- 8565676
TI  - [Disorders of the cranio-spinal junction].
AB  - Seventy-three patients were treated due to cranio-cerebral junction disorders
      between 1980 and 1993. All patients were categorized into three groups depending
      on the disorder type: congenital (38%), traumatic (47%), or neoplastic (15%). In
      every group character of the lesion, neurological symptoms and indications for
      surgical or conservative management were analyzed. The outcome was following:
      neurological status was improved in 24 cases, in 30 cases the condition was
      stabilized, progressed in 18 cases and 1 patient died.

PMID- 8565677
TI  - [Injuries of the cervical spine and spinal cord in patients with ankylosing
      spondylitis--diagnosis using magnetic resonance imaging].
AB  - Magnetic resonance (MR) imaging results in 8 from 14 ankylosing spondylitis
      patients treated of traumatic cervical spine and spinal cord injuries are
      presented. Focal changes within spinal cord were most common among complications
      (62%), epidural hematoma was found in 50% of cases. Neurological status has
      worsened in patients with post-traumatic spinal cord pathology.

PMID- 8565678
TI  - [Results for surgical treatment of kyphoscoliosis complicated with spinal cord
      injury].
AB  - Results of surgical treatment of kyphoscoliosis complicated with spinal cord
      injury are presented. There were 16 congenital kyphoscoliosis, 5 idiopathic ones
      and 4 in course of neurofibromatosis. Increased spasticity was present in 2
      patients, spastic paresis in 12 and 11 patients were paraplegic. In 24 cases
      spinal decompression was performed, in 6 years old boy with spasticity the convex
      side of the curve was fused. Neurological symptoms ceased in 13 cases, marked
      improvement was achieved in 6 patients, partial recovery in 1 case, in 5 cases no
      improvement was accomplished. One patient died 6 weeks after operation due to
      heart attack. Analysis of results achieved indicates, that surgery in most of
      kyphoscoliosis complicated with spinal cord injury offers good prognosis.

PMID- 8565679
TI  - [Spondylitis caused by Salmonella infantis--case report].
AB  - A case of 61 years old male with diagnosis and bacteriological confirmation of
      lumbar spondylitis caused Salmonella infantis is presented. The condition turned
      out to be fatal despite antibiogram based antibiotic therapy.

PMID- 8565680
TI  - [Results of surgical treatment for inveterate thoraco-lumbar and lumbar spine
      injuries with neurologic complications].
AB  - The method and results of surgical treatment for inveterate thoraco-lumbar spine
      injuries with neurological impairment in 31 patients are presented. All the
      patients were operated on. The mainstay of the procedure was anterior
      decompression from posterior-lateral approach. Symptoms abated or marked
      improvement occurred in more than half of the cases and partial recovery was
      noted in one fourth of them what confirms indications for surgery in these cases.

PMID- 8565681
TI  - [Changes in the subcapital growth plate due to avascular necrosis after treatment
      for congenital hip dislocation in radiologic, tomographic and magnetic resonance
      examinations].
AB  - The aim of this investigation was to compare magnetic resonance imaging and
      radiography in detecting subcapital growth plate changes due to avascular
      necrosis after treatment for congenital dislocation of the hip. MRI was done in
      16 patients (21 hips) aged 8-12 (mean 10 years), treated because of CDH.
      Radiographs were also done in all cases. Comparison between these two imaging
      modalities revealed superiority of MRI in both imaging of normal subcapital
      physis and imaging of its disorders.

PMID- 8565682
TI  - [Densitometric evaluation of the proximal femur after cemented hip prosthesis].
AB  - Results of DEXA densitometry evaluation of the proximal femur in 12 patients
      after cemented total hip replacement are demonstrated. Bone mineral density of
      the femur was measured using the dual energy absorptiometry Lunar DPX. Assessment
      was performed in the 3rd or 4th postoperative day, after 3rd, 5th and 12th week,
      after 6 and 9 months following surgery. A decrease in bone density around
      prosthetic stem ranging from 15% to 30% of the primary level was observed already
      in the third month after operation. The process continued and the values after 9
      months were significantly lower then initial ones.

PMID- 8565683
TI  - [Strength of leg and foot muscles after surgical treatment for clubfoot].
AB  - In 50 congenital clubfeet (in 28 children aged 62-126 months) operated on with
      subtalar release from dorsolateral and posteromedial approach isometric strength
      of flexors, extensors, pronators and supinators was assessed with tensometry. All
      the muscular groups showed decreased momentum if compared to normal foot. The
      smallest deficit was observed in plantar flexors. Better results were accompanied
      by greater muscular strength, but statistically significant relation existed
      between strength of dorsal flexors and the quality of result. Postoperative
      calcaneus position did not influence the strength of dorsal or plantar flexors of
      the foot. Additional lengthening of FHL and FDL decreased the strength of plantar
      flexion.

PMID- 8565684
TI  - [Our five year experience in using the Molskich compression-distraction
      apparatus].
AB  - The paper presents five years experience in using the Molskich compression
      distraction apparatus compatible with ZESPOL screws. A series of 51 patients was
      reviewed. Thirty-four cases of nonunion were managed using gradual controlled
      compression. Shortened limb was elongated in 4 patients (from 4 cm to 8 cm). In 6
      cases late correction of inaccurate closed ZESPOL fixation in tibial fractures
      was done. In remaining 7 cases Molskich fixator was applied primarily for tibial
      fracture fixation. Good results in 50 cases proved usefulness of the device and
      encouraged us to present our observations.

PMID- 8565685
TI  - [Septic arthritis in newborns and infants--clinical epidemiology].
AB  - Septic arthritis in 99 newborns and 58 infants was analyzed epidemiologically.
      Multiple localization of septic process has been found in 37.4% of newborns and
      16.0% of infants included in this study. The hip joint, knee and shoulder were
      affected most frequently in both groups. In 45.2% of newborns septic condition of
      the skin and in 37.1% otitis media was the source of infection. In infants septic
      arthritis was related to otitis media in 36.8%, septic condition of the skin in
      23.3% and respiratory tract infection also in 23.3%. Staphylococcus aureus was
      the most frequent joint aspirate culture finding.

PMID- 8565686
TI  - [Chronic recurrent multifocal osteomyelitis--personal experience].
AB  - Chronic recurrent multifocal osteomyelitis is a rare entity with obscure
      etiology. A review of literature concerning clinical appearance, diagnostics and
      management of this condition is presented. Own material embraces a group of 7
      children who have chronic recurrent multifocal osteomyelitis. Mean follow-up was
      2.5 years. On the basis of results achieved the authors believe this condition is
      of good prognosis and should be differentiated with chronic osteomyelitis and
      neoplastic changes.

PMID- 8565687
TI  - [The life of Albert Wojciech Adamkiewicz--part I].

PMID- 8565688
TI  - [Infection and monitoring in obstetrics].

PMID- 8565689
TI  - [Detection of intrauterine transmission of human cytomegalovirus by nested
      polymerase chain reaction].
AB  - OBJECTIVE: Using nested polymerase chain reaction (PCR) to detect Intrauterine
      transmission of human cytomegalovirus (HCMV). METHODS: Ninety one cases of
      pregnant women were devided into three groups according to their gestational
      stages. In the first and second trimesters, they terminated pregnancy
      voluntarily. HCMV-DNA in maternal and cord blood as well as placenta were
      detected respectively by nested PCR. RESULTS: In the first trimester, 20 out of
      30 cases were infected, Intrauterine transmission occured in 8 of the 20 infected
      mothers (HCMV-DNA were found in the chorionic villus). In the second trimester,
      21 out of 30 cases were infected, 7 of them transmitted HCMV to their fetus
      through placenta. In this term, the placenta infection rate is 40% (12/30). In
      the third trimester, 23 out of 31 cases women infected HCMV, 18 of them
      transmitted HCMV to their fetus through placenta, the placenta infection rate is
      66.67% (20/30). The congenital infection rate is 58.06% (18/31), much higher than
      the reported levels marked by cord sera IgM and (or) infants viremia.
      CONCLUSIONS: HCMV transmitted from mother to infant mainly through placenta.
      Nested PCR provides a valuable method that can detected virus infection not
      limited by virus reproduction state and human immuno-reaction ability.

PMID- 8565690
TI  - [Clinical observation on vertical transmission of human papillomavirus].
AB  - OBJECTIVE: To observe the possibility of maternal-fetal vertical transmission of
      human papillomavirus (HPV) via amniotic fluid. METHODS: Specimens of cervical
      secretions from 30 pregnant women were obtained during the third trimester before
      rupture of membrane, and specimens of pharyngeal secretions of their neonates
      were obtained 12-48 hours after birth. Amniotic fluids were collected in 13
      pregnant women during cesarean section. The presence of HPV types 6, 11, 16, 18,
      31, 33, 35, 38 deoxyribonucleic acid were detected by consensus polymerase chain
      reaction. RESULTS: HPV deoxyribonucleic acid was found in 16 cervical specimens,
      14 pharyngeal specimens and in 3 amniotic fluids, the positive rate was 53.3%,
      46.7%, 23.1% respectively. The pharyngeal specimen was also HPV positive in one
      of the three neonates from the amniotic fluid positive mothers. CONCLUSION: The
      results indicate that HPV can be transmitted in utero through amniotic fluid and
      cesarean section can not protect the neonates against vertical transmission
      completely.

PMID- 8565691
TI  - [Clinical observation on perinatal Chlamydia trachomata infection].
AB  - OBJECTIVE: To screen antigen of genital chlamydia trachomata (CT) in pregnant
      women and to study its clinical characteristics, treatment and transmission to
      the newborns. METHOD: Monoclone antibody immuno-fluorescence was employed in
      assaying. RESULTS: Positive incidence of CT infection during pregnancy was 86
      cases (26.88%), of whom 47/64 cases (73.44%) treated with traditional Chinese
      herbs for 2 weeks became negative. The other 22 were not treated because either
      they were too near to term (21 cases) or had local allergic reaction (1 case).
      Incidence of positive CT in newborns from untreated mothers was 81.82%, treated
      and became negative was 23.40%, treated but still positive was 88.24%.
      CONCLUSION: Antenatal treatment is of importance in preventing intrapartum
      transmission of CT from mother to child. The data indicated that treatment with
      traditional Chinese herbs was effective.

PMID- 8565692
TI  - [Effect of obstetric factors on neonatal hypoxic-ischemic brain injuries].
AB  - OBJECTIVE: To determine the effect of high risk obstetric factors on neonatal
      hypoxic-ischemic brain injuries. The obstetric factors were investigated,
      including maternal complications during pregnancy and labor, the mode of
      delivery. METHODS: Intensive B-ultrasound brain monitoring in 211 newborns within
      the first 48 hours of life was carried out. The abnormalities were followed up by
      B-ultrasound. We assessed the extent of hypoxic-ischemic brain injuries with two
      kind of types, mild and severe. The mild type included 1-2 degree intracranial
      hemorrhage and the local hypoxic-ischemic encephalopathy. The severe type
      included 3-4 degree intracranial hemorrhage and extensive cerebral edema.
      RESULTS: Thirty-nine cases (18.5%) were diagnosed intracranial hemorrhage and 22
      cases (10.4%) were diagnosed hypoxic-ischemic encephalopathy (HIE) or cerebral
      edema. The total positive rate was 28.9%. Of the positive cases, 67.2% were mild
      brain injuries without clinical symptoms. Those cases need no medical treatment
      and recovered in a natural course. The rates of brain injuries in groups of
      pregnancy induced hypertension, fetal distress, neonatal asphyxia and premature
      newborns, were 46.1%, 48.9%, 66.7% and 71.4% respectively. It suggested that high
      risk obstetric factors were closely related to neonatal brain injuries. 15.9% of
      positive cases were from normal mothers without any obstetric complications. The
      brain injuries in those cases were mild. CONCLUSIONS: The study showed that as a
      non-invasive procedure, B ultrasound brain examination is necessary for newborns
      with perinatal high risk factors of brain injuries. The study also suggested that
      perinatal care and systematic fetal monitoring were key-points for reduction of
      neonatal brain injuries.

PMID- 8565693
TI  - [The preliminary study of insulin resistance in pregnancy induced hypertension].
AB  - OBJECTIVE: To observe the changes of glucose metabolism in late pregnancy and to
      reveal the relationship between insulin resistance and pregnancy induced
      hypertension (PIH). METHODS: The 75g oral glucose tolerance test (OGTT) was
      performed in 30 cases with PIH (37-41 weeks gestation), 30 cases of normal
      pregnancy and 12 non-pregnant women. The levels of serum glucose, insulin and C
      peptide were measured by radioimmunoassay, and the areas under the curve (AUC)
      were calculated. RESULTS: There were significant increases of the peak level or
      AUC of insulin in PIH (61.42 +/- 48.72, 137.12 +/- 81.12 mIU/L) and in normal
      pregnant group (70.46 +/- 58.42, 150.37 +/- 104.76 mIU/L) compared with non
      pregnant controls (17.12 +/- 11.03, 34.38 +/- 16.01 mIU/L) (P < 0.01), however,
      they had a similar glucose levels before or after GTT (P > 0.05). Furthermore,
      there was no correlationship between systolic or diastolic blood pressure and the
      fasting insulin or the AUC. CONCLUSIONS: Insulin resistance and hyperinsulinemia
      were found in late pregnancy, but the changes of insulin resistance in PIH cases
      was not significant. So, there was no definitive relationship between insulin
      resistance and the rising of blood bressure of PIH.

PMID- 8565694
TI  - [Relationship between chlamydial infection in female genital tract and tubal
      infertility].
AB  - OBJECTIVE: To detect the incidence of chlamydial infection in female genital
      tract and it's relationship with tubal infertility. METHODS: Fourty-eight
      infertile women underwent laparoscopies were divided into study group (n = 32)
      and control group (n = 16). Samples were taken from the upper genital tract
      (including endometrium, tubal fimbriae, peritoneal fluid and pelvic adhesion) and
      lower genital tract (cervix). The monoclonal direct immunofluorescent method was
      used to assay chlamydia trachomatis the results of these two groups were
      compared. RESULTS: The positive percentage of cervical clamydial infections
      between the two groups were not significant lydifferent (P > 0.05). But there
      showed a significant difference between the two groups if compared by the
      incidence of the whole genital tract 32.5% and 10.2% (P < 0.01). The tubal
      positive percentage is 66.7% in the study group. Which is the highest among other
      locations such as cervix, endometrium, etc (P < 0.05). CONCLUSION: This study
      indicates that fallopian tube is a high prevalent site of chlamydial infection,
      and chlamydial infection in female genital tract is a principal pathogenic factor
      of tubal infertility. Early laparoscopy for tubal infertility and chlamydia
      trachomatis sampling is the key method for early diagnosis and treatment of
      chlamydia trachomatis.

PMID- 8565695
TI  - [Study of autologous bone marrow transplantation in the treatment of gynecologic
      carcinoma].
AB  - OBJECTIVE: To investigate the role of autologous bone marrow transplantation
      (ABMT) in patients with gynecologic carcinoma treated by high-dose chemotherapy.
      METHODS: This was a presentation of four patients with ovarian carcinoma, two
      patients with primary fallopian tubal carcinoma, and 5/6 of them clinically
      staged as III and IV, treated with combination chemotherapy of cytoxan and
      carboplatin by intraperitoneal and intravenous infusion, the dose being 2.5-5
      times those employed conventionaly. Autologous bone marrow collection and storage
      were conducted under strictly sterile conditions. Chemotherapy was given pre- and
      post-operatively and ABMT was performed immediately after chemotherapy. Careful
      follow-up was observed at monthly intervals. RESULTS: All of the six patients
      tolerated the treatment well, with no death within a median follow-up of 26
      months (range 1532). Five of them lived more than 6 months with no evidence of
      disease. Two patients without gross residual tumor, who could not tolerate
      conventional chemotherapy which had to be discontinued, successfully received
      high-dose chemotherapy, supported by ABMT. All four patients with gross residual
      tumor benefited by immediate clinical remission after treatment. Median survival
      for all patients was 28 months (range 1253), median survival for stage IV
      patients was 24 months (range 1230). CONCLUSIONS: Patients subjected to high-dose
      chemotherapy supported by ABMT are exempted from suffering the cyclic multiple
      courses of chemotherapy, repeated or long-term hospitalization and may lead a
      life of good quality.

PMID- 8565696
TI  - [Comparison between the roles of aminoglutethimide and hydroxyprogesterone
      caproates in the treatment of endometrial cancer].
AB  - OBJECTIVE: To compare the changes of serum levels and tissue receptor levels of
      estrogen and progesterone as well as histopathological changes following
      treatments of endometrial cancer with aminoglutethimide (AG), progesterone
      caproate, or a combination of both. METHOD: Thirty-nine patients of endometrial
      cancer were treated with hydroxyprogesterone caproate, AG or combination of both,
      and their effects were compared. RESULT: It was observed that: (1) the
      administration of AG gave a fall of estradiol and progesterone serum levels;
      hydroxyprogesterone caproates therapy increased the level of progesterone; and
      following the combination treatment, higher progesterone and lower estradiol
      levels were found (P < 0.05), (2) treatments by AG as well as by combination
      therapy brought about a considerable fall of the positive rate of ER and PR in
      tissues (P < 0.05), (3) histological changes showed inhibition of cell growths in
      all three types of treatment, secretory cells and decidual reaction were shown
      under the influence of hydroxyprogesterone caproates, the changes in combination
      therapy mainly complied with those in AG treatment. CONCLUSION: The results
      suggested that AG was effective in treating patients with endometrial cancer,
      resulting in changes of endocrine environments and inhibition of cell growth by
      mechanism different from that of hydroxyprogesterone caproates.

PMID- 8565697
TI  - [Sarcoma of vulva: a clinical retrospective analysis of 10 cases].
AB  - OBJECTIVE: To study the characteristics of vulval sarcoma and its relationship
      between treatment methods and prognostic factors. METHODS: 10 cases of vulval
      sarcoma were retrospectively reviewed in this paper. Prognostic factors such as
      tumor volume, grade and treatment methods were analysed. RESULTS: The age
      incidence sarcoma of the vulva was 20 years younger than that of carcinoma of the
      vulva. The treatment of choice was operation combined with chemotherapy or
      radiotherapy. The effectiveness of chemotherapy or radiotherapy alone was not
      conclusive. CONCLUSION: Primary treatment with thorough surgery is very
      important. The prognosis is related with tumor volume, grade and treatment
      methods.

PMID- 8565698
TI  - [Advances in the research on the pathogenesis, diagnosis and treatment of uterine
      adenomyosis].

PMID- 8565699
TI  - DNA organization and polymorphism of a wild-type Drosophila telomere region.
AB  - Telomeres at the ends of linear chromosomes of eukaryotes protect the chromosome
      termini from degradation and fusion. While telomeric replication/elongation
      mechanisms have been studied extensively, the functions of subterminal sequences
      are less well understood. In general, subterminal regions can be quite
      polymorphic, varying in size from organism to organism, and differing among
      chromosomes within an organism. The subterminal regions of Drosophila
      melanogaster are not well characterized today, and it is not known which and how
      many different components they contain. Here we present the molecular
      characterization of DNA components and their organization in the subterminal
      region of the left arm of chromosome 2 of the Oregon RC wild-type strain of D.
      melanogaster, including a minisatellite with a 457bp repeat length. Two distinct
      polymorphic arrangements at 2L were found and analyzed, supporting the Drosophila
      telomere elongation model by retrotransposition. The high incidence of terminal
      chromosome deficiencies occurring in natural Drosophila populations is discussed
      in view of the telomere structure at 2L.

PMID- 8565700
TI  - Molecular characterization and cytogenetic analysis of highly repeated DNAs of
      lake trout, Salvelinus namaycush.
AB  - The chromosomes of lake trout (Salvelinus namaycush) contain a considerable
      amount of heterochromatin located at the centromeres and/or telomeres of several
      chromosomes, including a sex-specific block located distally on the X chromosome.
      In order to investigate further the repetitive DNAs of lake trout, genomic DNA
      from a female was size fractionated (<600 bp) with the restriction endonuclease
      AluI and fragments were cloned into the bacteriophage M13. A total of 42 clones
      were isolated. Relative copy number of individual inserts within the lake trout
      genome was estimated by Southern analysis. Twelve clones were determined to be
      highly repetitive and were chosen for further investigation. Inserts of these
      clones contained sequences similar to the AluI/RsaI, EcoRI/DraI, DraI/BstEII, and
      MboI/BglII families reported from Arctic char (Salvelinus alpinus). The
      chromosomal location of several of these fragments was determined in lake trout
      by fluorescence in situ hybridization (FISH). Two related AluI/RsaI sequences
      (Type A, approximately 140 bp, and Type B,approximately 120 bp) showed
      differential hybridization. Type A hybridized to the centromeres of all
      metacentric as well as several acrocentric chromosomes. Type B hybridized to the
      centromeres of most acrocentric chromosomes. A sequence with homology to the
      EcoRI/DraI family hybridized to the centromeres of several acrocentric
      chromosomes. Sequences with partial similarity to the DraI/BstEII family
      hybridized to the major rDNA sites (nucleolar organizer regions, NORs) and
      several minor telomeric sites. The interstitial and telomeric heterochromatin of
      lake trout, including that of the X chromosome, appears to comprise sequences
      belonging to the MboI/BglII family.

PMID- 8565701
TI  - Characterization and chromosomal location of two repeated DNAs in three Gerbillus
      species.
AB  - Two tandemly repeated DNA sequences of Gerbillus nigeriae (Rodentia) (GN1 and
      GN2) were isolated and characterized. Both share a 36bp repeated unit, which
      includes a 20bp motif also found in primate alphoid and other repeated DNAs. The
      localization of GN1 and GN2 sequences on metaphase chromosomes of three Gerbillus
      species, G. nigeriae, G. aureus and G. nanus, was studied by fluorescence in situ
      hybridization (FISH). In the G. nigeriae and G. aureus karyotypes, which were
      shown to possess large amounts of heterochromatin and to have undergone multiple
      rearrangements during evolution, both GN1 and GN2 sequences were observed at
      various chromosomal sites: centromeric, telomeric and intercalary. In contrast,
      the karyotypically stable G. nanus, which does not possess large amounts of
      heterochromatin and seems to be a more ancestral species, possesses only GN1
      sequences, localized in the juxtacentromeric regions.

PMID- 8565702
TI  - Cytogenetics of an intrachromosomal transposition in Neurospora.
AB  - Knowledge of intrachromosomal transpositions has until now been primarily
      cytological and has been limited to Drosophila and to humans, in both of which
      segmental shifts can be recognized by altered banding patterns. There has been
      little genetic information. In this study, we describe the genetic and
      cytogenetic properties of a transposition in Neurospora crassa. In Tp(IR-
      >IL)T54M94, a 20 map unit segment of linkage group I has been excised from its
      normal position and inserted near the centromere in the opposite arm, in inverted
      order. In crosses heterozygous for the transposition, about one-fifth of
      surviving progeny are duplications carrying the transposed segment in both
      positions. These result from crossing over in the interstitial region. There is
      no corresponding class of progeny duplicated for the interstitial segment. The
      duplication strains are barren in test crosses. A complementary deficiency class
      is represented by unpigmented, inviable ascospores. Extent of the duplication was
      determined by duplication-coverage tests. Orientation of the transposed segment
      was determined using Tp x Tp crosses heterozygous for markers inside and outside
      the transposed segment, and position of the insertion relative to the centromere
      was established using quasi-ordered half-tetrads from crosses x Spore killer.
      Quelling was observed in the primary transformants that were used to introduce a
      critical marker into the transposed segment by repeat-induced point mutation
      (RIP).

PMID- 8565704
TI  - A reassessment of Y chromosomal behaviour in germ cells and Sertoli cells of the
      mouse as revealed by in situ hybridisation.
AB  - In situ hybridisation experiments were carried out to reappraise the state of
      condensation of the Y chromosome in germ cells and Sertoli cells of the mouse.
      Previous work had suggested that all testicular cells showed a condensed Y
      chromosome prior to the adult stage. We now demonstrate that, although the Y
      chromosome is condensed in pre-pubertal Sertoli cells, it is greatly expanded in
      primordial germ cells (gonocytes). An expanded Y-signal is first seen in Sertoli
      cell nuclei at or around day 21 of postnatal development, coinciding with the
      first appearance of spermatids in the germinal epithelium.

PMID- 8565705
TI  - Nucleolar cycle and localization of NORs in early embryos of Parascaris
      univalens.
AB  - During early embryogenesis of the nematode Parascaris univalens (2n=2) the
      processes of chromatin diminution and segregation of the germ and somatic cell
      lineages take place simultaneously. In this study we analyzed the nucleolar cycle
      in early embryos, both in germinal and somatic blastomeres, by means of silver
      staining and antibodies against the nucleolar protein fibrillarin. We observed an
      identical nucleolar cycle in both types of blastomeres, hence, the chromatin
      diminution process has no effect on the nucleolar cycle of somatic blastomeres.
      We report the existence of outstanding differences between this cycle and those
      previously reported during early embryogenesis of other species. There is a true
      nucleolar cycle in early embryos that shows a peculiar nucleolar disorganization
      at prophase, and a preferential localization of prenucleolar bodies only on the
      euchromatic regions during nucleologenesis. Moreover, fibrillarin does not form a
      perichromosomal sheath in metaphase or anaphase holocentric chromosomes, probably
      owing to their special centromeric organization. The number and location of
      nucleolus organizer regions (NORs) in the chromosomal complement have been
      determined using silver impregnation, chromomycin A3/ distamycin A staining, and
      fluorescent in situ hybridization using an rDNA probe. There are only two NORs,
      one per chromosome, and these are located in the middle of the euchromatic
      central regions. This location implies that no rDNA sequences are lost in
      blastomeres after chromatin diminution. Moreover, the constant presence of two
      nucleoli in somatic blastomeres suggests that NORs are not affected during the
      fragmentation of euchromatic regions when this process occurs.

PMID- 8565703
TI  - A Bkm-associated human y-chromosomal DNA is conserved and transcribed in the
      testis of mouse.
AB  - Y chromosome associated genes and repetitive sequences are continually viewed
      from the point of view of their possible involvement in sex determination and in
      the evolution of such a mechanism, thus sustaining an interest in the
      identification of novel sequences to gain newer insights. Here we have used the
      highly conserved class of Bkm repeats to isolate its associated sequences from
      the Y chromosome under the assumption that these sequences could be involved in
      sex determination and might also reflect the evolutionary status of the Y
      chromosome. Towards this end we have screened a genomic library enriched with
      human Y chromosome DNA with Bkm. One of the positive clones, C65, has a
      pericentromeric location on the Y chromosome and is present in a number of human
      sex-reversed XX males. The 10.5kb insert of clone C65 has been further subcloned
      (pFI, pFII, pFIII, pFIV). The subclone pFIII is present in both sexes in human
      and mouse, whereas pFIV is primate specific and present in both sexes. pFII
      contains sequences homologous to Bkm. pFI is conserved in mouse and man, but is Y
      specific only in primates. Although present in both sexes in mouse, pFI is
      transcribed specifically in the male testis suggesting that it may be involved in
      the process of sex determination or testis differentiation and spermatogenesis.

PMID- 8565706
TI  - Further insights on chromosomal pairing of autopolyploids: a triploid and
      tetraploids of rye.
AB  - Chromosomal pairing of one triploid and three tetraploid plants of rye, Secale
      cereale, was analyzed by electron microscopy in surface-spread prophase I nuclei
      and compared with light microscopic observations of metaphase I cells. Prophase I
      is characterized by: (i) the weak alignment showed by the three or four
      unsynapsed or partially homologous synapsed axes; (ii) the low number of pairing
      partner switches (PPSs) displayed by both trivalents and quadrivalents; and (iii)
      the existence of complex multivalents in which up to 13 chromosomes in the
      triploid and 22 chromosomes in the tetraploids were involved. However, only few
      heterologous chromosomal associations were maintained at metaphase I. The results
      obtained are discussed under the assumptions of the random end pairing model with
      some modifications.

PMID- 8565707
TI  - Chiasma frequency, distribution and interference maps of mouse autosomes.
AB  - Chiasma frequencies were analysed and chiasma positions measured in
      diakinesis/metaphase I autosomal bivalents from oocytes and spermatocytes of F1
      hybrid C3H/HeHx101/H mice. Twenty chromosome size ranks, including the
      presumptive X bivalent, could be distinguished in oocytes, and nineteen autosomal
      ranks plus the XY pair spermatocytes. Overall, mean cell chiasma frequencies of
      the two sexes did not differ significantly once the contribution of the
      presumptive X bivalent and the XY pair were taken into account. Sex related
      differences in chiasma distribution patterns were evident, however. In
      monochiasmate bivalents, the chiasma was most commonly located interstitially in
      oocytes while in spermatocytes it could be either interstitial or distal. In
      dichiasmate bivalents, the chiasmata tended to be more centrally located in
      oocytes than in spermatocytes. Minimum inter-chiasma distances did not appear to
      show any great variation in chromosome pairs of different sizes, however, mean
      inter-chiasma distances did increase with the bivalent length. The minimum-inter
      chiasma distance data suggest that chiasma interference is complete over a
      chromosomal segment equating to approximately 60Mb. Measurement of the positions
      of chiasmata along chromosome arms open up the possibility of producing chiasma
      based genetic maps for all the autosomes of the mouse.

PMID- 8565708
TI  - [Ambulatory blood pressure monitoring in clinical application].

PMID- 8565709
TI  - [Autonomic nervous activity at episodes of myocardial ischemia in patients with
      coronary artery disease by heart rate power spectral analysis].
AB  - Heart rate power spectral analysis in 44 patients with coronary artery disease
      was obtained from 24-hour dynamic electrocardiogram. 195 episodes of transient
      myocardial ischemia that was defined as horizontal or down sloping depression of
      the ST segment of > or = 0.1 mV and lasted for > or = 2 minutes were studied. The
      area of low frequency components (LF, 0.02-0.10 Hz) representing predominontly
      sympathetic tone with some contribution from the parasympathetic tone and that of
      high frequency components (HF, 0.15-0.40 Hz) representing mainly parasympathetic
      tone and the value of LF/HF on 4 minute heart rate power spectral graph at the
      deepest depression of ST segment were compared with that before the episode of
      myocardial ischemia. The area of HF of fast rate myocardial ischemia occurring in
      night reduces significantly (P < 0.001), the value of LF/HF increases markedly (P
      < 0.05) and the area of LF increases slightly. The results suggest that there is
      a change of autonomic nervous activity during the episode of fast rate myocardial
      ischemia in night, parasympathetic nervous tone decreases markedly, there may be
      secondary increase of sympathetic nervous activity.

PMID- 8565710
TI  - [The significance of high-density lipoprotein subfractions and triglycerides in
      predicting coronary artery disease].
AB  - Serum Lipid profiles, including high-density lipoprotein (HDL) and its
      subfractions HDL2 and HDL3 were obtained in 78 cases undergoing coronary
      angiography. Coronary artery disease (CAD) was present in 51 patients and absent
      in 27. We used a scoring methold of CAD to reflect the extent or narrowing of
      coronary artery. The largest difference between the two groups was observed in
      HDL2 Cholesterol with a mean of 0.37 mmol/L in patients with CAD as compared with
      0.49 mmol/L in normal subjects (P < 0.001) and in TG (1.85 mmol/L vs 1.16 mmol/L)
      as well. Smaller difference was found in TC (5.9 mmol/L vs 4.87 mmol/L, P <
      0.05). No singnificant difference was found in serum HDL (P > 0.05). Multivariate
      regression analysis revealed that the most powerful indenpendent variable
      associated with the extent of CAD was HDL2 cholesterol and triglyceride. The
      score of CAD was significantly correlated with HDL2-c (r = 0.32 P < 0.01) and TG
      (r = 0.34 P < 0.01). It is shown that high serum level of TG (> 1.6 mmol/L) and
      low serum level of HDLC2 (< 0.37 mmol/L) were the strengest predictors of
      presence and extent of CAD.

PMID- 8565711
TI  - [Dynamic changes of the platelet granule membrane glycoprotein level in patients
      with acute myocardial infarction before and after thrombolysis].
AB  - Platelet granule membrane glycoprotein (GMP-140) level was measured by using 125I
      labelled monoclonal antibody in 37 patients with acute myocardial infarction
      before and after thrombolytic therapy. In a nonthrombolysis group, it was shown
      that platelet GMP-140 increased significantly at the moment of admission and
      reached peak value 48 hours after AMI attack, then it decreased gradually and
      returned to baseline on the fifth day. In the thrombolysis group, with the
      patency of infarct related arteries, it dropped quickly (1-6 hours) after
      thrombolytic therapy; if the infarct related arteries were not patent, platelet
      GMP-140 increased rapidly after thrombolytic therapy and reached the highest at 6
      hours, then it returned to baseline on the third day. It is suggested that the
      changes of platelet function could play an important role in thrombus formation
      and lysis; the rapid decrease of the number of GMP-140 molecules on platelet
      surface might be a new index for the pateacy of infarct related arteries.

PMID- 8565712
TI  - [Clinical significance of fibrinolytic system defectiveness in exercise induced
      myocardial ischemia and its mechanism].
AB  - Plasma levels of tissue type plasminogen activator (tPA), plasminogen activator
      inhibitor (PAI), fibrinogen (Fg), thromboxane B2 (TXB2), 6-ketoprostaglandin F1
      alpha (6-keto-PGF1 alpha), renin activity (PRA) and angiotensin II (ANGII) were
      assayed in 18 patients with coronary heart disease and 11 healthy subjects before
      and after submaximal treadmill exercise test according to "Bruce programme". All
      patients showed significant (> or = 50%) stenosis of at least one branch of the
      coronary arteries in coronary angiography and normal levels of serum
      trinitroglycerin. Drugs of dipyridamole, heparin, warfarin and aspirin were not
      administered to the patients two weeks before the test. The results were as
      follows: (1) Plasma PAI activity and Fg levels in 12 patients with positive test
      were remarkablly higher than in the remaining 6 subjects with negative test in
      the CHD group and in the control before and after exercise. Plasma tPA antigen
      changed in a reverse way. (2) Plasma levels of TXB2, PRA and ANGII in the
      positive test subgroup of CHD were higher than in the negative test subgroup and
      in the control after exercise, but differences of the parameters among the three
      groups were insignificant before exercise. The study suggests that defectiveness
      of fibrinolytic system in CHD patients was shown mainly as disorder of tPA-PAI
      equilibrium and that decreased fibrinolytic activity and increased PAI in
      exercise-induced myocardial ischemia have relations with activation of platelets
      and renin-angiotensin system.

PMID- 8565713
TI  - [A study on the clinical classification of high altitude heart disease].
AB  - The clinical data of 514 cases of high altitude heart disease (HAHD) were
      reported, 62 cases of them were autopsied. According to the clinical
      characteristics and pathological changes, of the myocardlum, a clinical
      classification of HAHD was suggested. There might be four clinical phases, i.e.
      aggravating, acute, subacute and chronic. Cases of HAHD with different onset time
      may show different clinical manifestations of these four phases.

PMID- 8565714
TI  - [Determination of procollagen III levels in serum and broncho-alveolar lavage
      fluid in patients with interstitial lung disease and its clinical significance].
AB  - Serum and broncho-alveolar lavage fluid (BALF) levels of procollagen III (PCIII)
      were determined in 26 patients with interstitial lung disease (ILD) and healthy
      subjects as controls. The results showed: (1) Levels of PCIII in serum and BALF
      were significantly higher in the patient group than those in the control group;
      (2) A highly positive correlation was found between PCIII levels and alveolar
      macrophage counts in BALF in the patient group. (3) PCIII level in BALF (albumin
      as a denominator) is higher than that in own serum both in control and patient
      group, the higher level of PCIII in BALF might be the result of local production.
      We are of the opinion that changes of PCIII level in serum and BALF might be
      helpful in the evaluation of the turnover of collagen in the lung.

PMID- 8565715
TI  - [The value of endoscopic ultrasonography in the diagnosis of ampullary
      carcinoma].
AB  - The value of endoscopic ultrasonography (EUS) for diagnosing ampullary carcinoma
      was assessed in 14 patients. The diagnostic accuracy, the chariacteristics of the
      images and the preoperative invasion of the carcinoma were studied. The results
      showed that: (1) The lesions were clearly demonstrated in all cases (100.0%) and
      the diagnostic accuracy of EUS was 78.6%, which was better than that of
      transabdominal ultrasonography and CT (P < 0.05), but similar to that of
      endoscopic retrograde cholangio-pancreatography (ERCP) (P > 0.05). Three patients
      with pancreatic carcinoma were misdiagnosed as ampullary carcinoma by EUS,
      because the carcinoma was situated at the head of the pancreas and infiltrated to
      the duodenal wall. (2) Hyperecho image was obtained in 81.8% of the cases and
      hypoecho image in 18.2% of the cases. (3) The accuracy of EUS in demonstrating
      the invasion of the carcinoma into the duodenal wall, common bile duct,
      pancreatic duct and the head of the pancreas was 83.3%, 66.7%, 50.0% and 33.3%
      respectively and the lymph node matastasis of the carcinoma was 100.0%.

PMID- 8565716
TI  - [Relationship between elevated plasma endothelin-1 level and renal function in
      patients with diabetic nephropathy].
AB  - Plasma endothelin-1 (ET-1) level was measured with radioimmunoassay in 33 normal
      subjects and 92 patients with different stages of diabetic nephropathy,
      consisting of 35 cases of diabetes mellitus with normal urinary albumin excretion
      (DM), 22 cases of incipient diabetic nephropathy (IDN), 22 cases of overt
      diabetic nephropathy (ODN), 8 cases with azotemia (DNa) and 5 cases with uremia
      (DNu). The results showed that plasma ET-1 levels in DNa and DNu groups (30.24 +/
      1.93 ng/L and 36.38 +/- 3.62 ng/L respectively) were significantly higher than
      those in other groups (P < 0.05); ET-1 level in ODN group (20.50 +/- 0.93 ng/L)
      was significantly higher than those in DM and IDN groups (P < 0.001); ET-1 level
      in IDN group was also significantly higher than that in DM group (17.79 +/- 0.74
      vs. 15.06 +/- 0.63 ng/L, P < 0.01); All the above values were significantly
      higher than that in normal subjects (7.08 +/- 0.22 ng/L) (P < 0.001). There was
      significant positive correlation between ET-1 level and HbA1c, systolic pressure,
      diastolic pressure, blood urea nitrogen, serum creatine, uAER and a significant
      negative correlation between ET-1 level and glomerular filtration rate. It is
      shown that progressive elevation of plasma ET-1 level is closely related with
      different stages of renal function impairment, suggesting strongly the role of ET
      1 in the development and progression of diabetic nephropathy.

PMID- 8565717
TI  - [A clinical and experimental study of L-form bacteria in 66 cases].
AB  - In order to study the relationship between the time for establishing the
      diagnosis of infectious diseases and L-form bacteria, a series of clinical
      specimens taken from 321 cases of patients suspected to have infection were
      collected. Besides routine bacterial culture, special culture for L-form bacteria
      was also performed. The results were as follows: the rate of positive routine
      bacterial culture was 10.90% (35/321); the rate of negative routine bacterial
      culture but positive L-form bacterial culture was 20.56% (66/321). In this study,
      L-form bacteria infection was treated with sensitive antibiotics and a
      satisfactory result was obtained. It is shown that L-form bacterial culture is
      very useful in detection of pathogenic bacteria and helpful to the therapy of
      infectious diseases. Ultrastructure organization of these bacteria was studied by
      using transmission electron microscope.

PMID- 8565718
TI  - [Effects of high concentration glucose on cell growth and matrix biosynthesis in
      human peritoneal mesothelial cells].
AB  - During CAPD, the peritoneal mesothelial monolayer is directly bathed in dialysate
      containing 1.50%-4.25% glucose. In this study, we separated and cultured
      mesothelial cells from human omentulum (HMC) to test the effects of glucose on
      cell growth and matrix biosynthesis. [3H] thymidine incorporation was
      significantly inhibited in cells grown in > or = 1.00% glucose, compared with
      cells grown in 0.10% glucose and RPMI-1640 alone. HMC incubated in RPMI-1640
      medium released trace fibronectin (FN) as measured by specific enzyme
      immunoassay, and FN level in supernatants was significantly increased when HMC
      grew in the media containing glucose more than 0.50%. Glucose induced inhibition
      of cell proliferation and increase of FN were time-and dose-dependent. Mannitol
      also achieved the same results, but its inhibitive effect on HMC proliferation is
      far less than that of isoosmolar glucose. These studies provide evidence for a
      multitude of direct effects of high concentration ambient glucose level on HMC
      growth and matrix biosynthesis, and raise the possibility that long-term exposure
      of HMC to high concentration glucose may induce disturbance in cell repair and
      metabolism, thus contributing to the formation of sclcerosing peritonitis in
      CAPD.

PMID- 8565719
TI  - [Antikeratin antibodies: another specific antibodies in rheumatoid arthritis
      patients].
AB  - Sera from 107 patients with rheumatoid arthritis (RA), 120 patients with other
      rheumatic diseases and 60 blood donors were tested with indrect
      immunofluorescence on the middle third of Wistar rat oesophagus as a substrate
      for the presence of antikeratin antibodies (AKA). By labelling the stratum
      corneum and stratum spinosum with IgG antibodies, three patterns of reaction were
      distinguished. Among them, only one pattern which showed an intense linear
      laminated fluorescence on stratum corneum and a weak fluorensence on stratum
      spinosum was valuable for the diagnosis of RA, with a specificity of 99% and a
      sensitivity of 23%. It was also found that they were not related to the presence
      of rheumatoid factor or anti-RA 33,000/36,000 antibodies. Thus, AKA might be
      another marker antibody in RA.

PMID- 8565720
TI  - [Progress in the interventional therapy of coronary disease].

PMID- 8565721
TI  - [Current status in the gene therapy of coronary restenosis after interventional
      therapy].

PMID- 8565722
TI  - [Identifying the existence of cultured human epidermal allografts with PCR
      techniques].
AB  - It is still controversial whether cultured human epidermal allografts can survive
      long or not because of the lack of convincing evidence to prove it. In this
      study, three PCR techniques for the individual identification were used to test
      the existence of cultured allogeneic keratinocytes when it has been transplanted
      to differents kinds of wounds. With these methods, the donor genetic marks were
      found in 27 biopsies of 16 patients who had cultured epidermal cells allografted.
      The longest biopsy time was 92 days after grafting. The results strongly
      indicated that the survival time of cultured epidermal allografts was prolonged.
      The advantage and disadvantage of using the PCR techniques were discussed and the
      fate of the cultured epidermal allografts could be determined if these techniques
      are used properly.

PMID- 8565723
TI  - [In vitro antibacterial activity of sulperazone on multi-resistant strains of
      bacteria from burn wounds].
AB  - Sulperazone (SLP), a combination of sulbactam (beta-lactamase inhibitor) with
      cefoperazone (CFP), was studied in vitro for its sensitivity to multi-resistant
      strains of bacteria isolated from burn wounds. The results showed that the
      sensitive rate of gram-negative bacteria to SLP was 77.3% (n = 163), higher than
      that of CFP (45.0%, n = 169) (P < 0.01). The rate of pseudomonas aeruginosa which
      was common among the gram-negative bacteria was 88.9% (n = 45), much higher than
      that of CFP (71.7%, n = 46) (P < 0.05). The rate of bacterium anitratum was 100%,
      and it was resistant to CFP (P < 0.01). The sensitive rate of gram-positive
      bacteria to SLP was 37.5% (n = 128) but to CFP was 24.6% (n = 126) (P < 0.05).
      The rate of staphylococcus aureus which was common in gram-positive bacteria was
      42.6% (n = 61), much higher than that of CFP (21.3%, n = 61) (P < 0.05). It is
      indicated that sulbactam inhibits most beta-lactamases produced by common
      bacterial pathogens and makes antibiotics restore the sensitivity to resistant
      strains. Sulperazone is promising in the treatment of burn infection.

PMID- 8565724
TI  - [The roles of platelet activating factor in intestinal mucosal barrier injury
      after burn].
AB  - In order to investigate the roles of platelet activating factor (PAF) in postburn
      intestinal barrier injury, the changes in intestinal mucosal potential difference
      (PD), intestinal PAF, Phospholipase A2 (PLA2), myeloperoxidase (MPO) and
      malondialdehyde (MDA) were measured in a model of rats with 30% TBSA III degrees
      burns. The results showed that the intestinal PAF level was significantly
      elevated after severe burn and was negatively correlated with the decrease of
      intestinal mucosal PD (r = -0.94, P < 0.01). PAF antagonist WEB 2170 treatment
      could significantly inhibite the increase of PAF in intestinal tissue, enhance
      intestinal mucosal PD, attenuate the levels of PLA2, MPO and MDA in intestinal
      tissue, and alleviate the pathological changes in ileal mucosa, compared with the
      burn group. The results suggest that PAF is an important factor causing postburn
      intestinal mucosal barrier injury, and activation of leukocyte and PLA2 as well
      as the release of superoxide are important intermediate mechanisms for PAF
      leading to intestinal mucosal injury.

PMID- 8565725
TI  - [Treatment of burned joints and functional recovery].
AB  - From 1979 to 1990, 33 operations on 29 patients with joint burn were performed by
      early debridement and primary repair with myocutaneous flaps. As a result, 29
      wounds healed by first intention. The healing rate of early operations performed
      within 10 days postburn was 95.2%, and that of the late operations delayed more
      than 10 days post-burn was only 75.0%. 31 among 33 joints (93.9%) recovered full
      range of movement, while the other 2 joints ended with only slight limitation of
      function. We suggest that the early debridement and primary repair with
      myocutaneous flap is the best choice for treatment of burned bone and joints.

PMID- 8565726
TI  - [Changes in myocardial ATPase activity and Ca2+ content in burned rats].
AB  - The myocardial ATPase activity and Ca2+ content were investigated in rats with
      full thickness skin burn injury of 30% TBSA. The results showed that there were
      significant inhibitions of Na+, K(+)-ATPase,Ca2+, Mg(2+)-ATPase, and Ca(2+)
      ATPase activities of myocardium after burn injury. The burn injury could result
      in increase of calcium content in myocardium. Burned rats also had a higher level
      of MDA in heart tissue when compared to controls. This study demonstrates that
      the membrane defects with respect to ATPase activity, oxygen free radical, and
      Ca2+ overload in myocardium may be associated with damage of myocardium after
      burns.

PMID- 8565727
TI  - [Changes in serum granulocyte colony-stimulating factor (G-CSF) in burned
      patients].
AB  - Serum G-CSF level was assayed in 20 burned patients (TBSA > or = 30%) 2 weeks
      postburn. In 11 of them plasma endotoxin was also measured. The results showed
      serum G-CSF level was increased in 87.5% (7/8) of burned patients with exceeding
      50% TBSA and in 58.3% (7/12) of patients with 30%-50% TBSA, and in the former it
      was earlier increased (1-5 day postburn) than the latter (5-11 day postburn).
      Serum G-CSF was increased in 90% of the burned patients with wound sepsis.
      Increased of serum G-CSF in burned patients, especially in those exceeding 50%
      TBSA, indicates the occurrence of sepsis.

PMID- 8565728
TI  - [Escharectomy during burn shock stage contributed to controlling or alleviating
      infectious complication].
AB  - Among 29 patients with extensive burn, 14 received escharectomy during the shock
      period, and the other 15 after 96 hrs. LPS and TNF were determined before and
      after escharectomy 3, 7, 14 and 21 PBD. Incidence of sepsis and subeschar
      bacterial count were analyzed. Clinical conditions were compared. The results
      showed that escharectomy during burn shock stage significantly reduced infectious
      complications in extensively burned patients. We believe that as long as general
      condition of the patient allowed, early removal of eschar was beneficial in
      reducing the threat of sepsis.

PMID- 8565729
TI  - [Immune function of red blood cell (RBC) in patients with obstructive jaundice].
AB  - Twenty-six patients with obstructive jaundice were investigated for RBC immune
      function. It was found that C3b receptor's E rosette forming rate in jaundiced
      patients was significantly lower than that of nonjaundiced patients, and the C3b
      receptor's E rosette forming inhibitory rate was higher than that of nonjaundiced
      patients. The RBC immune function disturbance may contribute to the postoperative
      sepsis in jaundiced patients.

PMID- 8565730
TI  - [Long-term effect of extended parietal cell vagotomy on patients' nutrition and
      digestive function].
AB  - In this study, 36 patients undergoing extended parietal cell vagotomy (EPCV) were
      compared with 30 patients with subtotal gastrectomy 7-14 years after surgery. The
      patients' nutritional status, gastric sectretion, gastrointestinal motility and
      intestinal absorption function were evaluated. The nutritional status was
      generally less satisfactory in 33. 3% patients with anaemia after gastrectomy and
      decrease of body weight in 54%. The patients after EPCV were all in good
      nutritional status, with no anemia; 56% of them had a body weight increase of
      more than 3kg. Therefore, the rationality of EPCV was estalished.

PMID- 8565731
TI  - [Ultrasonic angiography in diagnosis of peripheral vascular disease].
AB  - The ability of Quickscan (QS) was studied to assess haemodynamically significant
      lesions in the iliac and femoro-popliteal arteries. Quickscan was prospectively
      and independently compared to digital subtraction angiography (DSA) of the iliac
      and femoro-poplited arteries. In 155 patients, 631 arterial segments were
      evaluated. A QS frequency ratio of greater than 1:3 had a sensitivity of 93% and
      a specificity of 85% in detecting stenosis > 50% diameter (75% area) reduction in
      the iliac artery as shown on DSA. The sensitivity and specificity for stenosis in
      the femoral and popliteal arteries were 85%, 96%, 82%, 98% respectively. In the
      detection of occlusion, QS had a sensitivity of 84% and a specifity of 98% in the
      iliac artery; 94%, 97%, in the femoral; and 94%, 85% in the popliteal arteries
      respectively. There was a significant correlation between the area reduction
      found by QS and the calf/brachial pressure index (CBI) (r = -0.77 P < 0.01). 35
      patients underwent successfully angioplasty based on QS findings. We conclude
      that quickscan can provide an inexpensive, quick and noninvasive screening
      technique for the routine initial assessment of peripheral vascular disease.

PMID- 8565732
TI  - [Excision of mid-lower rectal carcinoma through abdomen and anogenital space].
AB  - 28 men with male mid and lower rectal carcinoma were treated by dissecting
      sigmoid colon and rectum in the abdomen through the anogenital space, which
      refers to the potential coronoid space located between the deep transverse
      perineal muscles and anal sphincter muscles. The rectal segment was pulled out
      through the anogenital space to accomplish resection and anastomosis outside the
      pelvic cavity. Follow-up for 9-57 months showed that 26 cases (92.9%) survived
      without recurrence of carcinoma and 1 had local recurrence. The advantages of the
      procedure include clear exploration, minimal trauma, super-lower anastomoses
      under direct vision, good recovery of defecating function, and less contamination
      of pelviccavity.

PMID- 8565733
TI  - [Postoperative residual intracranial aneurysms].
AB  - From January 1991 to 1994, 99 aneurysms in 91 patients were clipped in the
      Neurosurgy Department of Beijing Tiantan Hospital. Six residual aneurysms were
      found by postoperative angiography. We analyzed these patients and concluded that
      the occurrence of residual aneurysms depends mainly on the location, size, type,
      neck width of the aneurysms, and their rupture during operation. According to
      this, we give opinions on how to prevent residual aneurysms and how to deal with
      them.

PMID- 8565734
TI  - [The delayed traumatic intracerebral haematomas].
AB  - The results of CT observation of 378 inpatients with head injury were reported.
      46 delayed traumatic intracerebral haematomas (DTICH) patients were found to have
      71 haematomas. The incidence of DTICH was 12.2%. 80.7% of DTICH patients were
      noted 48 hours after injury. Most of them were young and middle aged persons. The
      places of baematomas were at the injured zones. The intracranial pressure
      continous monitor is useful to judge the DTICH during the early stage. Surgical
      operation is proposed for the patients with many haematomas and displaced central
      tissue. The haematomas should be cleansed for the frequently occurring haematoma
      patients. The death rate of the example was 17.4%, which was lower than 44%-71%
      reported elsewhere.

PMID- 8565735
TI  - [Diagnosis and treatment of interrupted aortic arch: report of 6 cases].
AB  - Six patients with interrupted aortic arch were operated on from Nov. 1986 to Jun.
      1992. 4 patients were type A and 2 type B. The result was good except a patients
      of type A died early after operation. Two-stage operation was performed for 4
      patients of type A, and 2 patients of type B accepted posterolateral incision.
      The aortic arch was constructed with artificial vessel. Cardiopulmonary bypass
      was set up with patients lying on back, then PDA was ligated and VSD closed.
      Pulmonary artery trunk reconstruction and VSD closing were performed. Three
      months after operation a patient died of septicemia caused by infection of
      incision.

PMID- 8565736
TI  - [Surgical treatment of familial acromegaly].
AB  - The annual incidence of the acromegaly is three cases per million, and that of
      the familial acromegaly is even far rarer. The number of familial acromegaly
      reported in the medical literature of all the world is fewer than 10 cases per
      year, and up till now none of such a patient has been reported in China. All the
      three cases of familial acromegaly reported here were from the same family, and
      showed typical clinical manifestations. They presented the history of acral
      enlargement, headache, amenorrhoea, elevated serum GH level, enlargement and
      erosion of pituitary fossa in X-ray and CT scan, and characteristic
      immunohistochemical findings of GH-secreting pituitary adenoma. All of them
      underwent successful transsphynoidal total removal of the pituitary adenoma, and
      recovered well by clinical, endocrine, and pathological criteria. An extended
      family tree of 65 members excluded consanguinous marriage and suggested that the
      mode of inheritance was irregular autosomal dominant.

PMID- 8565737
TI  - [The expression and significance of proliferating cell nuclear antigen/cyclin in
      cholangiocarcinoma and gallbladder carcinoma].
AB  - The expressions and significance of proliferating cell nuclear antigen (PCNA)
      were studied by immunohistochemical method in 40 cases of gallbladder carcinoma
      and 42 cases of cholangiocarcinoma. The counting score of positive cells was
      significantly lower in cases of well-differentiation, histologic grade I and
      without metastasis than that in cases of poor-differentiation, histologic grade
      III and with metastasis. Close correlations were found between the survival time
      and the counting score of PCNA. These results suggested the cholangiocarcinoma
      and gallbladder carcinoma with highly positive cell rate might have poor
      prognosis, and PCNA might be an important marker reflecting the biological
      behavior and having prognostic value.

PMID- 8565738
TI  - [Arthrography of the wrist joint].

PMID- 8565739
TI  - [Development and uses of porous-coated hip prostheses].

PMID- 8565740
TI  - Prevalence, etiology, and prognostic significance of upper gastrointestinal
      hemorrhage in diabetic ketoacidosis.
AB  - We reviewed the discharge records of all diabetic ketoacidosis hospitalizations
      over 30 months for the presence of clinically significant upper gastrointestinal
      hemorrhage. Of 284 hospitalizations in 193 patients, hemorrhage occurred in 26
      hospitalizations (9%) in 25 patients (13%). None required invasive therapy to
      achieve hemostasis, and there were no bleeding recurrences and no deaths due to
      bleeding. Endoscopy in eight revealed esophagitis in all (five had erosions or
      ulcerations), one Mallory-Weiss tear, five with gastritis (mild in four), four
      with duodenitis (one erosive), one duodenal ulcer, and no gastric ulcers.
      Hemorrhage patients had a longer diabetes duration (14.85 vs 9.16 years, P <
      0.02), and more nephropathy (40% vs 11%, P < 0.001), retinopathy (28% vs 12%, P <
      0.03) and gastroparesis (36% vs 10%, P < 0.002) than those without hemorrhage.
      Ulcer medication (42% vs 23%, P < 0.03) or anticoagulant (12% vs 1%, P < 0.005)
      but not nonsteroidal antiinflammatory drug usage (12% vs 12%) was higher in the
      hemorrhage group. Admission glucose (P < 0.02), BUN (P < 0.04), and creatinine (P
      < 0.02) levels were higher in hemorrhage patients, but arterial pH, serum
      ketones, hemoglobin, platelet count, and coagulation values were not. Hemorrhage
      patients required more blood transfusions (27% vs 10%, P < 0.003) and intensive
      care unit admissions (69% vs 43%, P < 0.009). Total (15% vs 3%, P < 0.003) and
      intensive care unit mortality (22% vs 6%, P < 0.026) were higher in the
      hemorrhage group. We conclude that upper gastrointestinal hemorrhage complicates
      9% of diabetic ketoacidosis hospitalizations. Blood transfusion may be required,
      but the bleeding is self-limited and not severe. The most common lesion is
      erosive esophagitis. Hemorrhage correlates with glucose level, admission to the
      intensive care unit, duration of diabetes, the presence of diabetic
      complications, and portends a high non-bleeding-related mortality.

PMID- 8565741
TI  - Observations on relationship between hypergastrinemia, multiple gastric
      carcinoids, and pancreatic mass.

PMID- 8565742
TI  - Frequent K-ras mutations in small bowel adenocarcinomas.
AB  - The reasons for the relatively rare occurrence of small bowel adenocarcinomas
      when compared to the high frequency of colonic adenocarcinomas are unknown.
      Activating mutations in the K-ras oncogene occur in about 40% of colonic
      adenocarcinomas, possibly reflecting the consequences of carcinogenic exposure.
      To study whether the low incidence of small bowel adenocarcinomas might be due to
      the absence of activation of cellular oncogenes in small bowel adenocarcinomas,
      we examined the frequency of K-ras mutations in small bowel adenocarcinomas. K
      ras mutations were determined using a polymerase chain reaction (PCR)-based
      method to detect codon 12 mutations by restriction fragment length polymorphism.
      PCR amplification was successful in six of nine small bowel adenocarcinoma
      samples, and revealed point mutations of K-ras at codon 12 in five of these six
      cases. We conclude that the small bowel might be exposed to carcinogens similar
      to those responsible for colorectal cancer, but may have developed protective
      mechanisms against cancer formation.

PMID- 8565743
TI  - Tissue potassium, selenium, and iron levels associated with gastric cancer
      progression.
AB  - The contents of 10 minor and trace elements in histologically confirmed gastric
      adenocarcinomas and their corresponding normal gastric mucosal tissues obtained
      from 39 patients at the time of gastric resection were simultaneously determined
      by instrumental neutron activation analysis. Specimens were irradiated by reactor
      neutrons and subsequently subject to direct analysis using a high-resolution HPGe
      gamma-spectrometer. Univariate analysis revealed that gastric cancer tissues had
      significantly higher concentrations of Fe, K, Mg, Na, Rb, Se, and Zn than normal
      gastric mucosal tissues. However, multivariate analysis found that Fe, K, and Se
      were independent elements that associated with gastric cancer. Upon further
      evaluation of their clinical significance, we found a high tissue K level was
      related to lymphatic duct metastasis. High Se tissue levels were linked to
      intestinal type adenocarcinoma. A positive correlation was found between high Fe
      levels and vascular involvement. These findings suggest that Fe and K are
      associated with gastric cancer progression. Se is involved in carcinogenesis of
      stomach in high-risk areas. The mechanisms that underlie the corresponding
      pathohistological features deserve further study.

PMID- 8565745
TI  - Spontaneous bacterial peritonitis complicating malignancy-related ascites.

PMID- 8565744
TI  - Effect of prostaglandin E1 on ammonia concentration in blood of patients with
      hepatic resection.
AB  - Plasma concentrations of ammonia were examined following prostaglandin E1 (PGE1)
      administration in 16 patients who received hepatectomy for hepatocellular
      carcinoma. PGE1 at 0.01-0.04 microgram/kg/min was administered for approximately
      24 hr during the perioperative periods. The ammonia concentration was reduced a
      day after the operation following intravenous administration of PGE1 in cirrhotic
      patients compared to noncirrhotic patients with or without PGE1 injection. Serum
      liver function scores, glutamic pyruvic transaminase, and total bilirubin
      concentrations were decreased after PGE1 administration. A similar ammonia
      response due to PGE1 was obtained after operation in cirrhotic patient when PGE1
      0.5 microgram/kg was administered intravenously for 30 min. These results suggest
      that PGE1 administration is useful in reducing the enhanced ammonia concentration
      associated with hepatic resection, and it is particularly effective in the case
      of liver cirrhosis.

PMID- 8565746
TI  - Possible involvement of Rab11 p24, a Ras-like small GTP-binding protein, in
      intracellular vesicular transport of isolated pancreatic acini.
AB  - Rab11 p24 is a Ras-like small guanosine triphosphate (GTP)-binding protein, and
      specific antibodies against it were newly developed to explore its function.
      Using the antibody, Rab11 p24 was shown to be abundant in rat pancreas as well as
      in most rat tissues. To explore the involvement of Rab11 p24 into the exocytotic
      process, the subcellular distribution of Rab11 p24 in rat pancreatic acini was
      evaluated also by use of the antibody. When the isolated acini were incubated
      with 1 x 10(-10) M cholecystokinin octapeptide (CCK-8) that induced the maximal
      stimulation, the amount of Rab11 p24 increased in the fractions of plasma
      membrane and zymogen granules, but decreased in the cytosol fraction. This
      redistribution was time-dependent and occurred within 1 min after the CCK-8
      stimulation and reached a maximal level within 2 min after the stimulation.
      Moreover, a light microscopic immunolabeling technique on the isolated rat
      pancreatic acini also revealed that higher immunoreactivity with Rab11 p24 was
      observed over the zymogen granule membrane under CCK-8 stimulation. The present
      results indicate that Rab11 p24 is translocated from cytosol to the membrane
      fraction during stimulation with CCK-8 and suggest that Rab11 p24 is involved in
      the intracellular vesicular transport of isolated acini.

PMID- 8565747
TI  - Hepatic mitochondrial and lysosomal alterations in acute experimental
      pancreatitis with ethanolic coetiology in rats.
AB  - In order to assess the cumulative effects of antecedent acute ethanol intake and
      acute pancreatitis on the liver, the mitochondrial respiratory functions and
      lysosomal membrane integrity of the liver were evaluated in taurocholate
      pancreatitis (AP) in rats, induced 6 hr after intragastric ethanol 40% (5 g/kg
      body wt). The oxygen consumption rate, RCR (respiratory control ratio), and ADP/O
      ratio were measured according to Estabrook. Fractional free activity of lysosomal
      hydrolases was assayed. RCR with glutamate + malate was most decreased at 12 hr
      of AP with partial improvement after 18 hr. The ADP/O ratio dropped maximally
      after 18 hr of AP. The fragility of lysosomal membranes increased significantly
      at 18 hr of AP. The antecedent ethanol intake abolished the partial restoration
      of RCR after 18 hr; however, it did not affect the ADP/O ratio or the integrity
      of lysosomal membranes impaired in AP at this time. In conclusion, the antecedent
      acute ethanol abuse could aggravate the liver mitochondrial deterioration, but
      not the lysosomal membrane labilization seen in AP.

PMID- 8565749
TI  - Evaluation of quantitative assay for antibody to hepatitis C virus core in
      patients treated with interferon.
AB  - We titrated antibody to hepatitis C virus (anti-HCV) core of serum samples from
      57 patients with chronic HCV infection, in an attempt to clarify the relationship
      between the level of HCV RNA and the outcome of interferon treatment. The
      patients studied were positive for both anti-HCV, by second-generation assay, and
      HCV RNA, by polymerase chain reaction, and had been treated with interferon for
      six months. Of the 57 patients, HCV RNA was eliminated in 16 by the time of
      discontinuation of interferon treatment (CR); in 19 this elimination was
      transient (PR) and for 22 elimination was nil (NR). The low HCV RNA level was
      accompanied by high titers of anti-HCV core while high HCV RNA levels were
      accompanied by low titers of anti-HCV core, with an inverse correlation (r = 
      0.322, P < 0.05). The mean titer of anti-HCV core before interferon treatment was
      324 units in CR, 205 in PR, and 168 in NR, with a correlation ratio of 0.382 (P <
      0.05). A decreased titer (more than 50%) was found in 68% of the CR. At the time
      of six-month follow-up, the anti-HCV core titers of CR had decreased by more than
      50%, compared to pretreatment titers, while in PR and NR, there was an increase
      to above the pretreatment titers, without increases in HCV RNA levels or
      worsening of the hepatitis. In conclusion, quantitative assay for anti-HCV core
      is useful to assess the status of HCV replication.

PMID- 8565748
TI  - High-dose interferon-alpha 2b for re-treatment of nonresponders or relapsing
      patients with chronic hepatitis C. A controlled randomized trial.
AB  - Relatively few patients with chronic hepatitis C treated with standard doses of
      interferon-alpha 2b (3 million units per week for 24 weeks) have a sustained
      response. Our aim was to evaluate whether higher doses of interferon would
      improve this rate of response. Twenty-four patients with chronic hepatitis C who
      had failed to respond to (N = 21) or had relapsed after (N = 3) an initial course
      of standard interferon therapy were randomized to 15 million units (N = 13) or
      22.5-30 million units per week (N = 11) for 24 weeks. Five of 13 subjects given
      15 million units per week and 3/11 of subjects given 22.5-30 million units per
      week had complete normalization of serum alanine aminotransferase levels during
      therapy. Five patients (24% who had not responded to standard interferon had a
      complete response to high-dose interferon during therapy. Only one patient had a
      sustained response, with normal serum alanine aminotransferase 24 weeks after
      stopping interferon. Six patients were withdrawn before completing treatment,
      five in the 22.5-30 million unit per week group. We conclude that higher doses of
      interferon ameliorate the severity of hepatitis in patients who failed to respond
      to or relapsed after standard interferon therapy, but are unlikely to produce a
      sustained response. High-dose therapy is associated with an increase in side
      effects.

PMID- 8565750
TI  - Chronic hepatitis C without anti-hepatitis C antibodies by second-generation
      assay. A clinicopathologic study and demonstration of the usefulness of a third
      generation assay.
AB  - To study the clinicopathologic features of hepatitis C viremic patients negative
      for hepatitis C antibodies (anti-HCV) by current second-generation assay, we
      categorized 139 consecutive histologically verified patients with chronic non-A,
      non-B hepatitis into three groups: 121 (87%) were positive for second-generation
      anti-HCV (group A); 10 (7%) were negative for second-generation anti-HCV but
      positive for HCV RNA (group B); and 8 (6%) were negative for both antibodies and
      viremia (group C). Six (60%) of group B patients could be, further detected by a
      new third-generation assay, but none of group C patients was third-generation
      anti-HCV-positive. The demographic features, mean peak serum alanine
      aminotransferase levels, HCV genotype distribution, and histologic changes were
      comparable among the three groups. The study indicates that most patients with
      chronic hepatitis C in Taiwan could be identified by current second-generation
      assay, and viremic but antibody seronegative patients were clinicopathologically
      similar to the seropositives. Most patients of the latter group could be
      diagnosed by a third-generation assay, indicating the usefulness of this assay.

PMID- 8565751
TI  - Impact of international autoimmune hepatitis group scoring system in definition
      of autoimmune hepatitis. An Italian experience.
AB  - We have reclassified 110 patients with autoantibody-positive cryptogenic chronic
      hepatitis according tot he aggregate scoring system proposed by the International
      Autoimmune Hepatitis Group for signs of hepatitis C virus (HCV) infection and the
      newly proposed terminology of "unclassified" chronic hepatitis. Anti-HCV and HCV
      viremia were assessed by second-generation assays and reverse transcription
      polymerase chain reaction. Immunomorphological and immunochemical
      characterizations of antinuclear, smooth, muscle, liver-kidney microsomal type 1,
      and liver cytosol type 1 autoantibodies were also performed. All 45 anti-HCV
      negative patients fulfilled the score criteria for the diagnosis of "definite" or
      "probable" autoimmune hepatitis (AIH). Eight anti-HCV-positive cases reached the
      score of "probable" AIH, whereas the remaining 57 cases were diagnosed as
      unclassified chronic hepatitis. The scoring system allows the correct
      identification of all autoimmune cases without HCV infection. Autoimmune
      hepatitis runs a more severe disease course than unclassified chronic hepatitis,
      whose clinical and histological features are similar to those of autoantibody
      negative chronic hepatitis C.

PMID- 8565752
TI  - Do concomitant diseases and therapies affect the persistence of ulcer symptoms in
      the elderly?
AB  - Risk factors of slow healing were previously researched in a large sample of
      duodenal (DU) and gastric ulcer (GU) patients over 65 years of age; persistence
      of ulcer symptoms was proven the most reliable factor in predicting nonhealing
      ulcer, while ulcer size was of importance only for DU. We aimed to complete the
      analysis, with a more careful evaluation of concomitant diseases and therapies.
      Ranitidine 300 mg daily was given for four to eight weeks to 310 GU and 699 DU
      patients. Ninety-three patients dropped out of the study; 79/294 gastric ulcers
      and 138/635 duodenal ulcers were unhealed after four weeks. Cardiovascular,
      gastrointestinal, and pulmonary disorders were the most frequent concomitant
      diseases; NSAIDs, cardiovascular drugs, and antihypertensives were the most
      frequent concomitant therapies. Esophagitis was diagnosed in 15.5% of patients.
      Ulcer healing was the major determinant of persistence of ulcer symptoms;
      esophagitis emerged as an important adjunctive and independent factor. Use of
      hypoglycemic agents in the whole sample and smoking habit (in GU) may have also a
      role. With persistence of ulcer symptoms removed from the analysis, ulcer size
      was the most constant factor affecting ulcer healing. NSAID use, cardiovascular
      disorders, esophagitis (in GU), and concomitant therapy with cardiovascular drugs
      (in DU) also play a role. In conclusion, persistence of ulcer symptoms, the major
      indicator of slow ulcer healing in the elderly, is independently affected also by
      the presence of esophagitis. Use of hypoglycemic agents and smoking habit may
      also have a role in persistence of ulcer symptoms. NSAIDs, cardiovascular
      disorders, cardiovascular drugs, and esophagitis affect ulcer healing, for which
      the most constant indicators remained persistence of ulcer symptoms and ulcer
      size.

PMID- 8565754
TI  - Nafcillin-associated hepatotoxicity. Report of a case and review of the
      literature.
AB  - Nafcillin is a semisynthetic penicillin that is generally well tolerated with few
      side effects. Hepatic complications are rare but have a potential for serious
      liver dysfunction. This unusual complication causes a predominantly cholestatic
      injury, which can persist for prolonged periods even after discontinuing the
      medication. The pathophysiology may include direct cytotoxicity or an immune
      mediate hypersensitivity. Treatment is generally supportive, except for severely
      symptomatic patients who may require steroids. We report a case of nafcillin
      associated hepatotoxicity and review the literature of this disorder.

PMID- 8565753
TI  - Nonalcoholic steatohepatitis. Clinicopathological comparison with alcoholic
      hepatitis in ambulatory and hospitalized patients.
AB  - This study reports a clinicopathological analysis of 105 patients whose liver
      histology showed a pattern of alcohol-like steatohepatitis. There were 32
      nonalcoholic, 21 asymptomatic ambulatory, and 52 hospitalized alcoholic hepatitis
      patients. Female sex, obesity, and diabetes predominated in nonalcoholics.
      Clinical and laboratory presentation were similar in nonalcoholics and ambulatory
      alcoholics, but different from the hospitalized alcoholics. Histology showed an
      increasing degree of severity of hepatocellular damage, Mallory bodies,
      neutrophil and mononuclear infiltration, and pericellular and portal fibrosis
      from the nonalcoholics to the hospitalized alcoholics, with ambulatory alcoholics
      displaying an intermediate degree of severity. Steatosis and glycogenated nuclei
      were prevalent in the obese, diabetic nonalcoholics, of whom 47% had significant
      fibrosis and 8% cirrhosis, the latter present in 38% and 89% of ambulatory and
      hospitalized alcoholic hepatitis (P = 0.0001), respectively. In asymptomatic
      subjects with suspected liver disease, a liver biopsy is the only way of
      establishing the type and severity of liver lesions.

PMID- 8565755
TI  - Portal vein thrombosis following endoscopic variceal sclerotherapy. Prospective
      controlled comparison in patients with cirrhosis.
AB  - The association between portal vein thrombosis (PVT) and prior endoscopic
      variceal sclerotherapy has been suggested but remains unproven. The aim of this
      study was to compare the incidence of PVT in patients who had received
      sclerotherapy for esophageal variceal hemorrhage to a control group of cirrhotic
      patients with portal hypertension who had not received sclerotherapy. Doppler
      ultrasound was used to assess PVT in 48 patients (group 1) who had received
      sclerotherapy for variceal hemorrhage as well as in 52 patients (group 3) with
      cirrhosis and portal hypertension who had not received sclerotherapy. Assessment
      of PVT was made at the time of surgery in 24 patients (group 2) who had received
      sclerotherapy for variceal hemorrhage, failed therapy, and had portacaval shunt
      surgery or received liver transplantation for liver failure. One patient had
      splenectomy for symptoms related to a massively enlarged spleen. The incidence of
      PVT in group 1 was 10%, in group 2 was 13%, and in group 3 was 10%. The incidence
      of PVT in the three groups was not significantly different statistically. In this
      controlled study of patients with cirrhosis and portal hypertension,
      sclerotherapy does not increase the incidence of PVT.

PMID- 8565756
TI  - Noninvasive variceal pressure measurement may be useful for predicting effect of
      sclerotherapy for esophageal varices.
AB  - This study assessed the relationship between variceal pressure and morphological
      findings and hemodynamics of esophageal varices as well as the effect of
      sclerotherapy. Esophageal variceal pressure was measured in 40 patients with
      portal hypertension, using a noninvasive method. Esophageal variceal pressures
      were significantly higher in moderate or large varices than they were in small
      varices. Variceal pressures were significantly higher in patients with red color
      signs on the varices than in those without. According to the percutaneous
      transhepatic portography, the structure of the esophageal varices was classified
      into two types: the bar type and the palisading type. The maximum variceal
      pressure was significantly higher in the bar type than in the palisading type. In
      patients who underwent more than five sessions of sclerotherapy, the variceal
      pressure was significantly higher than in those receiving less than four
      sessions. These results suggest that variceal pressure may well reflect the
      vascular pattern and be useful for predicting the effect of sclerotherapy.

PMID- 8565757
TI  - Influence of administration of long-chain polyunsaturated fatty acids on process
      of histological recovery in liver cirrhosis produced by oral intake of
      thioacetamide.
AB  - Patients with liver cirrhosis frequently show some degree of protein-energy
      malnutrition and obviously require nutritional support. In this study, the
      treatment of rats consisted of the ad libitum oral intake of a 300 mg/liter
      thioacetamide solution, used as drinking water for four months. Thioacetamide
      treatment produced a severe alteration in the plasma fatty acid profile with
      significant decreases of these, which mimicked changes described in human
      cirrhosis. This hepatotoxic agent causes nodular cirrhosis, with loss of the
      normal architecture of the liver and disruption of the vascular pattern. The goal
      of the study was to evaluate the influence of n-3 and n-6 series long-chain
      polyunsaturated fatty acid dietary supplementation in experimental animals and to
      assess the effects of those dietary components on structural recovery in the
      liver. Significant increases of saturated and monounsaturated fatty acids as well
      as n-6 polyunsaturated fatty acids were seen only in the animals given the n-6
      polyunsaturated fatty acid supplemented diet. However, only rats given the
      standard diet exhibited some degree of histological regeneration.

PMID- 8565758
TI  - Hepatitis C virus replication is associated with expression of transforming
      growth factor-alpha and insulin-like growth factor-II in cirrhotic livers.
AB  - The molecular role of hepatitis C virus (HCV) in liver disease has yet to be
      clarified. In this study, we analyzed the relationship of HCV replication with
      mRNA expression of growth factors and mutation of tumor suppressor gene, ie,
      transforming growth factor-beta 1 (TGF-beta 1), which promotes cirrhotic changes;
      TGF-alpha, insulin-like growth factor-II (IGF-II), which are both related to
      hepatocyte transformation; and tumor suppressor gene p53, which is associated
      with HCC progression. A semiquantitative RNA polymerase chain reaction (RNA-PCR)
      was used to analyze genetic expression in 31 cirrhotic liver specimens from
      patients with HCV. In order to detect HCV replication, the minus-strand RNA of
      HCV, which serves as a template for the synthesis of genomic plus-strand RNA, was
      examined. The expression of the growth factors was semiquantified by RNA-PCR, and
      the mutation of p53 was detected using PCR-single-strand conformation
      polymorphism. According to the semiquantitative analysis, HCV replication was not
      associated with the expression of TGF-beta 1 but was significantly so with the
      overexpression of TGF-alpha (r = 0.74) and IGF-II (r = 0.65) in the HCV-positive
      cirrhotic livers. No mutation of p53 was recognized in any of the samples. Our
      investigation thus suggested that the replication of HCV might mediate the
      coexpression of TGF-alpha and IGF-II and act as a possible initiating factor for
      hepatocarcinogenesis.

PMID- 8565759
TI  - Fiberoptic technique for 24-hour bile reflux monitoring. Standards and normal
      values for gastric monitoring.
AB  - Physiologic bile reflux was assessed in 27 in vivo test with healthy volunteers
      to define a standardized protocol and normal values for 24-hour enterogastric
      bile reflux monitoring (protocol with supine, upright, and meal phases and a free
      diet avoiding alcohol, smoking, and coffee, evaluation with different thresholds
      of absorbance units: 0.14, 0.25). In vitro tests with bile-sodium solutions
      demonstrated a linear dependence of absorbance for bilirubin up to 600
      mumol/liter (range of the fiberoptic device: 0.0-1.0). Fluids and food might
      interfere with absorbances below 0.25 (exception: coffee). In vivo bile often
      remains in the stomach for more than 1 hr; these events were defined as reflux
      episodes. The upper limits for physiologic bile reflux are a percentage of total
      time of bile reflux of 28.2% and an average absorbance during a reflux episode of
      0.62 (95th percentile with threshold 0.25). Comparing bile with pH monitoring
      (absorbance > 0.25 and/or pH > 4), an increase of bilirubin was found most
      frequently with constant pH (45%) or an increase of pH with constant bilirubin
      (36%). The hypothesis was drawn that bile and duodenal or pancreatic secretions
      may separately contribute to duodenogastric reflux.

PMID- 8565760
TI  - Effects of sulglycotide on inflammation and epithelial cell turnover in active
      Helicobacter pylori+ chronic gastritis. A pilot study.
AB  - The effects of Sulglycotide were evaluated in a pilot study of active H. pylori+
      atrophic gastritis. Ten informed patients (mean age 51 +/- 13 years) entered a
      double-blind study. Five received Sulglycotide 400 mg three times a day for one
      year, the other 5, placebo. At 0, 30, 90, 270, and 360 days of treatment,
      patients underwent endoscopic examinations with multiple biopsies. Morphometric
      studies (number of inflammatory cells and percent gland volume), morphologic
      studies (according to the Sydney system), and flow cytofluorimetry were performed
      in all cases. Compared to findings in the placebo group, patients treated with
      Sulglycotide showed a reduced number of inflammatory cells and an increase in
      gland volume 120 days after treatment. While the difference was not statistically
      significant, the trend was confirmed by the morphologic patterns. Flow
      cytofluorimetry revealed an increase in the percentage of cells in the G2 phase
      (full maturation) and a parallel drop in the S phase (premitotic synthesis) in
      the Sulglycotide group only in the first three months. These data would appear to
      indicate an acceleration of gastric epithelial cell maturation and a decrease in
      the inflammatory infiltrate under the effect of Sulglycotide.

PMID- 8565761
TI  - Importance of fungus colonization in failure of silicone rubber percutaneous
      gastrostomy tubes (PEGs).
AB  - Silicone rubber PEG tubes or replacements were recovered from 111 patients and
      examined for blockage, dilatations, tears, breaks, or loss of elasticity. All
      irregularities were stained and examined for fungus using lactophenol cotton blue
      stain. The intraabdominal portion of the PEG failed from obstructions, loss of
      elasticity, or tears related to fungus colonies in 36% of cases. An additional
      34% were colonized with fungi but did not fail. On frozen section, the fungus
      invaded the wall of the tubing. The extraabdominal PEG tubing failed from fungi
      in 12, and 10 additional tubes had colonizations. Nine tubes had distal clogging
      with crystalline material that is believed to arise from medication. Fungus tube
      failure occurred in 37% of the tubes in place 250 days and in 70% of tubes in
      place 450 days. Fungus is an important cause of PEG failure; recommendations are
      provided to maintain tube patency.

PMID- 8565762
TI  - Is Helicobacter pylori a cause of nonulcer dyspepsia.

PMID- 8565763
TI  - Relationship between gastric and gallbladder emptying and refilling in normal
      subjects and patients with H. pylori-positive and -negative idiopathic dyspepsia
      and correlation with symptoms.
AB  - Gastric and gallbladder emptying and refilling was studied in 10 normal subjects
      and in 38 dyspeptic patients. H. pylori was determined in each dyspeptic on
      mucosal antral biopsy performed during endoscopy. Gastric and gallbladder
      emptying was evaluated by real-time ultrasonography. Normal subjects were
      evaluated after two solid-liquid meals of 340 kcal and 680 kcal. Dyspeptics were
      studied after the 340-kcal meal only. For each subject and patient, minimum
      gallbladder volume and percentage of gastric emptying at this point was
      determined. Gastric and gallbladder slope was also drawn, and the crossing point
      between the two slopes identified. In normal subjects with the 340-kcal and 680
      kcal meal, minimum gallbladder volume occurred for a similar percentage of
      gastric emptying. The crossing point between the two slopes was computed at the
      same percentage of gastric and gallbladder refilling with both meals. With the
      680-kcal meal, however, peak gallbladder contraction and the crossing point
      between the two slopes occurred significantly later than with the 340-kcal meal
      (P < 0.05). In dyspeptics with the 340-kcal meal, the parameters evaluated were
      similar to the ones computed in controls after the meal of 680-kcal, suggesting
      delayed gastric emptying and gallbladder refilling. The presence or absence of H.
      pylori and symptom score were not correlated with any of the parameters studied.

PMID- 8565764
TI  - Gastric mucosal adaptation to diclofenac injury.
AB  - Adaptation occurs to the gastric injury produced by nonsteroidal antiinflammatory
      drugs during continued dosing. The aim of this study was to identify
      characteristics of this phenomenon that might help in the search for underlying
      mechanisms. The time frame for onset and offset of adaptation of diclofenac
      (damage assessed planimetrically) was examined in rats. Adaptation to oral
      diclofenac took three to five days to develop, and persisted for up to five days
      after the last dose. It was also demonstrable after subcutaneous dosing or when
      injury was measured by a change in mucosal potential difference. Diclofenac
      adapted rats were protected against injury induced by subsequent exposure to
      ethanol, indomethacin, aspirin, or piroxicam, indicating that adaptation is not
      specific to injury by the adapting agent. This cross-adaptation was dose
      dependent and characterized histologically by a reduction in deep damage. In
      conclusion, gastric adaptation to diclofenac is mediated by mechanisms that take
      several days to develop and be lost. The route of administration appears to be
      unimportant, but the development of both adaptation and cross-adaptation is
      influenced by dosage size.

PMID- 8565765
TI  - Hypergastrinemia increases proliferation of gastroduodenal epithelium during
      gastric ulcer healing in rats.
AB  - We investigated if hypergastrinemia exerted any influence on the proliferation of
      gastroduodenal epithelium during the healing of ulcers in rats. A mucosal ulcer
      was induced in the corpus region of the stomach in three groups of rats, which
      were then given vehicle, omeprazole (400 mumol/kg/day), or gastrin-17 (60
      nmol/kg/day) for three or six days. A fourth group of unoperated rats served as
      controls. One hour before killing, [3H]thymidine was injected. The ulcer margin
      and corresponding control tissues were excised and processed for light
      microscopic determination of epithelial labeling index (LI), mitotic index, and
      apoptotic index. LI was also determined in other parts of the gastroduodenal
      mucosa. Three and six days after the ulcer operation, the LI in the vehicle
      treated ulcer rats was significantly increased in the ulcer margin and in the
      duodenum, in comparison with the intact controls. In the ulcer margin, the
      mitotic index was significantly increased, in parallel with the LI; the apoptotic
      index remained at the control level. The LI in the ulcer margin was increased
      further after administration of omeprazole or gastrin-17, which elevated the
      plasma gastrin levels by 5-15 times. It is concluded that hypergastrinemia may
      increase cell proliferation in the ulcer margin, which may accelerate the rate of
      healing.

PMID- 8565766
TI  - Mechanisms for cytoprotection by vitamin U from ethanol-induced gastric mucosal
      damage in rats.
AB  - A comparison was made of the effects of a nonsulfhydryl compound, vitamin U
      (methylmethioninesulfonium chloride, MMSC), and a sulfhydryl compound, cysteine
      (Cys), with regard to the inducement of acute gastric mucosal damage in the
      presence and absence of N-ethylmaleimide (NEM), a sulfhydryl-blocking reagent.
      The effects of MMSC, Cys, or NEM on gastric mucin content were examined using a
      newly developed biochemical method. MMSC and Cys inhibited mucosal damage due to
      50% ethanol. The preinjection of NEM had no effect on cytoprotection of
      prostaglandins, but prevented the effects of Cys and MMSC. MMSC and Cys increased
      surface mucin content but lessened that of deep mucin. NEM decreased surface
      mucin and increased deep mucin. It thus follows that sulfhydryl compounds
      accelerate the secretion of deep mucin and accumulate surface mucin. The
      cytoprotective mechanism of MMSC may thus be mediated by sulfhydryl compounds,
      and the increase in surface mucosal mucin may possibly be related to
      cytoprotection.

PMID- 8565767
TI  - Cold-restraint- and TRH-induced ulcer models demonstrate different biochemical
      and morphological manifestations in gastric and hepatic tissues in rats. Role of
      calcitonin.
AB  - In the present study, two ulcer models--central thyrotropin-releasing hormone
      (TRH) injection and cold-restraint stress (CRS) application--were compared.
      Animals were treated either with salmon calcitonin (sCT) or saline
      intracerebroventricularly (ICV) before CRS exposure or ICV TRH injection. In both
      models, besides ultrastructural properties, ulcer indexes and lipid peroxidation
      (LP) and glutathione (GSH) levels of liver and stomach were determined. While TRH
      treatment did not affect GSH and LP levels of the stomach and led to a slight
      decrease in hepatic GSH levels, CRS induced a marked reduction in gastric and
      hepatic GSH and an increase in LP levels of both tissues. sCT pretreatment
      prevented the reduction of gastric and hepatic GSH levels and morphological
      damage of both tissues in the CRS group. However, the same treatment did not
      prevent the TRH-induced reduction of hepatic GSH levels and, interestingly, it
      worsened the ultrastructural disturbances in the liver. Although sCT prevented
      macroscopic ulcer formation in both models, it did not totally reverse the
      microscopic effects of TRH.

PMID- 8565768
TI  - Biofeedback training in children with functional constipation. A critical review.
AB  - Many uncontrolled studies suggest that biofeedback training is an effective
      adjunctive therapy in improving the outcome of functional constipation and/or
      encopresis in children. This could not be confirmed in controlled studies. Adding
      biofeedback training after conventional treatment had failed did not provide
      benefits. The results of biofeedback treatment in children with functional
      constipation and/or encopresis are disappointing.

PMID- 8565769
TI  - Increased resting lipid oxidation in Crohn's disease.
AB  - Resting energy expenditure (REE) was measured by indirect calorimetry and body
      composition was assessed by both direct (bioimpedance) and indirect
      (anthropometry) methods in 20 hospitalized patients with biopsy-proven ileal
      Crohn's disease and in a group of 16 healthy volunteers matched for sex, age, and
      height with the patient group. The Crohn's disease activity index was below 120
      in all patients studied, who were treated with a low dose of corticosteroids (0.2
      0.3 mg/kg body wt of prednisone). The average weight of Crohn's patients was
      significantly lower than that of controls (55.70 vs 70.50 kg, P < 0.001) due to
      both lower fat mass (9.97 vs 18.30 kg, P < 0.001) and lower lean body mass (45.72
      vs 52.20 kg, P < 0.02). The average REE was significantly higher in the control
      group (1785.42 +/- 7.503 vs 1559.1 +/- 48.39 kcal/day, P < 0.001). However, these
      differences disappeared when REE was normalized by lean body mass (LBM) (34.49 +/
      2.56 vs 34.704 +/- 3.75 kcal/kg LBM P = NS). The nonprotein respiratory quotient
      was significantly lower in the patient group (0.823 +/- 0.031 vs 0.882 +/- 0.012,
      P < 0.025), indicating an increased lipid oxidation. This increased lipid
      oxidation might explain the reduced fat stores found in the group of Crohn's
      patients, suggesting also that a sufficiently lipid-rich diet could be useful in
      their nutritional management.

PMID- 8565770
TI  - Health-care-seeking behaviors related to bowel complaints. Hispanics versus non
      Hispanic whites.
AB  - Health-care-seeking behaviors related to bowel complaints may vary between ethnic
      groups. A survey of a nonpatient population in El Paso, Texas, was conducted in
      order to examine differences in health care behavior related to bowel
      dysfunction, and in the perception of health and bowel function, in Hispanics and
      non-Hispanic whites. Data from 905 subjects who were either Hispanic (580) or non
      Hispanic white (325) given a forced-choice, self-report questionnaire were used
      for analysis. Data on health care behavior variables were studied using logistic
      regression, in ethnic and gender groups, controlling for age and socioeconomic
      status. A log-linear analysis was applied to health perception variables in
      ethnic and gender groups. Hispanics were less likely than non-Hispanic whites to
      have seen a physician for bowel symptoms (P < 0.02). Of the subjects with
      symptoms compatible with irritable bowel syndrome, Hispanics were less likely to
      have seen a physician (P < 0.05). More Hispanics reported buying folk remedies (P
      < 0.001), and herbal teas were taken more often to maintain good bowel function
      (P < 0.02) and to treat bowel problems (P < 0.005). Additionally, Hispanics had a
      poorer perception of their health in general (P < 0.001), reported more concern
      about their health (P < 0.02), more concern about bowel function (P < 0.001), and
      more time spent attending to bowel function (P < 0.001). Therefore, data on
      health-care-seeking behaviors related to bowel dysfunction showed that Hispanics
      were less likely than non-Hispanic whites to seek health care for bowel
      complaints and that Hispanics were more likely to self-medicate with folk
      remedies to maintain good bowel function. The perception of health and bowel
      function is in part determined by ethnic differences.

PMID- 8565771
TI  - Is small bowel biopsy necessary in adults with suspected celiac disease and IgA
      anti-endomysium antibodies? 100% positive predictive value for celiac disease in
      adults.
AB  - The comparative diagnostic value of IgA anti-endomysium and IgA antigliadin
      antibodies in adults with histologically confirmed celiac disease is reported.
      Sera from 144 adult patients (without concurrent dermatitis herpetiformis or IgA
      deficiency) who underwent small bowel biopsy were analyzed for both IgA anti
      endomysium and IgA anti-gliadin antibodies. Nineteen patients (13%) had celiac
      disease. The presence of IgA antiendomysium antibodies had a sensitivity of 74%
      and a specificity of 100%. The positive and negative predictive values were 100%
      and 96%, respectively, and the diagnostic accuracy was 97%. In contrast, IgA anti
      gliadin antibodies had positive and negative predictive values of 28% and 96%,
      respectively, with a diagnostic accuracy of 71%. Based on these data, we suggest
      that small bowel biopsy is not necessary to diagnose celiac disease in
      symptomatic adults with IgA antiendomysium antibodies. Due to a negative
      predictive value of 96%, some symptomatic adults lacking anti-endomysium
      antibodies will not be correctly diagnosed without small bowel biopsy.

PMID- 8565773
TI  - Wide gastric antrum and low vagal tone in patients with diabetes mellitus type 1
      compared to patients with functional dyspepsia and healthy individuals.
AB  - Autonomous neuropathy in patients with diabetes is associated with dysmotility
      and abdominal discomfort. The disturbances resemble to some extent those seen in
      patients with functional dyspepsia. To gain further insight into the disorders,
      we compared patients with long-standing diabetes, patients with functional
      dyspepsia, and healthy individuals with respect to abdominal symptoms, width of
      gastric antral area, and autonomic nerve function. We investigated 42 type I
      diabetic outpatients by structured interview for abdominal discomfort,
      ultrasonography of the gastric antrum, assessment of vagal and sympathetic nerve
      function by respiratory sinus arrhythmia and skin conductance, and measurement of
      blood sugar and HbA1c. Immediately after a standard meal of soup with meat, 21
      (50%) of the 42 patients with diabetes complained of abdominal discomfort (pain,
      bloating, fullness), which was significantly less frequent (95% CI of difference
      0.03-0.5) than previously seen in patients with functional dyspepsia (76%), and
      significantly more frequent (95% CI of difference 0.3-0.6) than that seen in
      healthy individuals (4%). Bloating was the most marked postprandial complaint.
      Mean fasting antral area was significantly wider in patients with diabetes (mean
      4.9 cm2, SD 1.7) compared to healthy individuals (mean 3.5 cm2, SD 1.2), 95% CI
      of difference 0.6-2.2 cm2. Mean postprandial antral area was 14.8 cm2 (SD 4.6) in
      the patients with diabetes, which is insignificantly wider than in patients with
      functional dyspepsia (mean 13.0 cm2, SD 4.0) but significantly wider (95% CI of
      difference 1.9-6.5 cm2) than that seen in healthy individuals (mean 10.6 cm2, SD
      3.8). The mean respiratory sinus arrhythmia was 0.7 beats/min (SD 0.7) in the
      patients with diabetes, which was insignificantly lower than that seen in
      patients with functional dyspepsia (2.1 beats/min, SD 4.5), and significantly
      lower (99% CI of difference 3.8-7.1 beats/min) compared to healthy individuals
      (6.2 beats/min, SD 3.8). It is concluded that patients with diabetes have a wider
      gastric antrum and more discomfort after a meal than healthy individuals.
      Compared to patients with functional dyspepsia, patients with diabetes have a
      wider postprandial antrum but fewer symptoms. The very low vagal tone seen in
      patients with diabetes may play an important role in the pathogenesis of their
      gastric motility disturbance and postprandial abdominal discomfort.

PMID- 8565772
TI  - Structural characterization of colonic cell types and correlation with specific
      functions.

PMID- 8565774
TI  - Utility of trace trifluoroacetic acid to enhance the quality of proton NMR
      spectra of xenobiotic metabolites.

PMID- 8565775
TI  - Relevance of tissue distribution studies and cytopharmacology: utility of
      radioassay combined with autoradiography.

PMID- 8565776
TI  - Metabolism of oral 9-cis-retinoic acid in the human. Identification of 9-cis
      retinoyl-beta-glucuronide and 9-cis-4-oxo-retinoyl-beta-glucuronide as urinary
      metabolites.
AB  - Data from a number of investigators suggest that the 9-cis-isomer of RA1 (9-cis
      RA) may be a promising agent in chemoprevention and treatment of certain types of
      cancer. Therefore, clinical studies on this retinoid have been initiated.
      However, up to now, no information has been published on the metabolism of 9-cis
      RA in the human. Herein, we report the first data on retinoid metabolism after
      multiple administration of 9-cis-RA (20 mg/day po) to human volunteers. After 2
      and 12-13 hr, plasma concentrations of 9-cis-RA and its metabolites 9,13-dicis
      RA, 13-cis-RA, and all-trans-RA were low. In contrast, dosing with 13-cis-RA
      yielded much higher plasma retinoid levels. Effects on plasma retinol
      concentrations did not become obvious after any drug treatment. Several retinoid
      metabolites were found in the urine of 9-cis-RA-treated individuals, and 9-cis
      RAG, as well as 9-cis-4-oxo-RAG, could be identified. After treatment with 9-cis
      RA, high concentrations of the administered drug were found in the feces, along
      with comparably low concentrations of 13-cis-RA, 9,13-dicis-RA, and all-trans-RA.
      Our report indicates that 9-cis-RA is either eliminated much more rapidly than 13
      cis-RA, or it is poorly absorbed, and presents the characterization of two
      urinary glucuronides.

PMID- 8565777
TI  - Reactivity of gemfibrozil 1-o-beta-acyl glucuronide. Pharmacokinetics of
      covalently bound gemfibrozil-protein adducts in rats.
AB  - Acyl glucuronides are electrophilic metabolites that are readily hydrolyzed,
      undergo intramolecular rearrangement, and mediate the covalent binding of many
      acidic drugs to endogenous proteins. Gemfibrozil is extensively metabolized to
      gemfibrozil acyl glucuronide in humans and rats. The aims of this study were to
      demonstrate the reactivity of gemfibrozil glucuronide, determine whether
      gemfibrozil formed covalently bound protein adducts in vivo, describe the
      pharmacokinetics of adduct formation, and examine the role of gemfibrozil
      glucuronide in adduct formation. Rats were administered 150 mg/kg gemfibrozil
      daily for up to 37 days and killed 1, 2, 5, 10, 19, and 37 days after
      commencement of dosing, and 1, 2, 3, 8, 17, and 30 days after cessation of
      dosing. Plasma, liver, kidney, and heart were examined for adduct formation.
      Plasma was quantitatively the most important site for formation of gemfibrozil
      protein adducts with mean (SE) steady-state concentrations of 31.40 (2.40) ng/mg
      protein attained by approximately the 10th day of dosing. Adduct half-life in
      plasma was 3.1 days, consistent with the elimination half-life of albumin. Mean
      (SE) kidney, liver, and heart steady-state adduct concentrations were 2.13
      (0.11), 0.89 (0.35), and 0.95 (0.07) ng/mg protein, respectively. The rate of
      gemfibrozil-protein adduct accumulation seemed greatest in liver, but was similar
      in kidney and plasma, with approximately 2x, 16x, and 30x accumulation,
      respectively, over the dosing interval. In all tissues, adduct half-lives were
      significantly greater than those of the noncovalently bound gemfibrozil or
      gemfibrozil glucuronide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8565778
TI  - Stereoselective reversible binding properties of the glucuronide conjugates of
      fenoprofen enantiomers to human serum albumin.
AB  - The stereoselective binding of fenoprofen enantiomers and fenoprofen glucuronide
      diastereomers to human serum albumin (HSA) was investigated using an
      ultrafiltration method. Fenoprofen glucuronides exhibit a considerable and
      stereoselective affinity to HSA, although less than seen for the parent drug. The
      (R)-glucuronide shows a higher affinity to HSA than the (S)-diastereomer. With
      the enantiomers, no significant difference could be detected. Diazepam and
      probenecid reduced the binding of the glucuronides, as well as that of the
      fenoprofen enantiomers. These results suggest that parent drug and its
      glucuronide metabolites occupy the same binding region on the albumin molecule.
      Both fenoprofen enantiomers, as well as racemic fenoprofen, are capable of
      reducing the extent of reversibly bound fenoprofen glucuronide.

PMID- 8565779
TI  - A comparison of mass balance, pharmacokinetics and disposition of [14C(U)]- and
      [125I]recombinant human interleukin-2 in cynomolgus monkeys.
AB  - Recombinant human interleukin-2 (rHuIL-2) has been metabolically labeled with 14C
      amino acids in Escherichia coli and affinity purified on a rHuIL-2 receptor
      affinity column. The radiolabeled molecule had a specific radioactivity of 238
      dpm/unit and the identical amino acid sequence and biological activity as
      unlabeled rHuIL-2. In this study, we used this labeled [14C(U)]rHuIL-2 and
      commercially available [125I]rHuIL-2 (identical in sequence to the [14C(U)]rHuIL
      2) to compare the mass balance, pharmacokinetics, and disposition in cynomolgus
      monkeys. After a single intravenous bolus dose of 4 x 10(5) units/kg, serum
      samples were collected for 7 days and examined for biological activity, total
      radioactivity, and by molecular size exclusion chromatography. Urine and feces
      were analyzed for total radioactivity. When analyzed for biological activity,
      both [14C(U)]- and [125I]rHuIL-2 exhibited the following pharmacokinetic
      parameters: terminal elimination half-life of 1-2 hr, AUC0-infinity ranged from
      2005 to 4659 units x hr/ml, clearance was 90-200 ml/hr/kg, and volume of
      distribution ranged from 103 to 163 ml/kg. Comparison of the pharmacokinetic
      profiles of the two radiolabels were very different from bioactivity, in that the
      elimination half-lives for radioactivity were approximately 8 days and 10 hr for
      [14C(U)]- and [125I]rHuIL-2, respectively. We conclude that the [14C(U)]rHuIL-2
      was metabolized to constituent amino acids and recycled into newly synthesized
      proteins from our size exclusion chromatography studies.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8565780
TI  - Characterization of an O-glucuronide metabolite of the CCK-B antagonist LY288513
      and its plasma levels in mouse, rat, and dog.
AB  - LY288513 [(4S,5R)-trans-N-(4-bromophenyl)-3-oxo-4,5-diphenyl-1-
      pyrazolidinecarboxamide] has been developed as a cholecystokinin-B antagonist for
      anxiolytic indications. In the drug disposition studies reported herein, we found
      LY288513 was metabolized rapidly in mice and rats to form a glucuronide adduct.
      This metabolite was isolated from rodent urine and further characterized to
      determine whether a ring-nitrogen or the oxygen atom in the pyrazolidinone
      nucleus of LY288513 was bonded to the glucuronide. Using 13C NMR plus two
      dimensional rotating frame Overhauser enhancement spectroscopy analysis and IR
      analysis of model compounds, we determined the metabolite was an O-glucuronide.
      The major elimination pathway for [14C]LY288513 was fecal, with > 75% of total
      radiocarbon excreted within 24 hr. Plasma levels for parent and metabolite in the
      three species varied substantially. The plasma half-life was significantly longer
      in dogs (approximately 12 hr) than mice (approximately 24 hr) or rats (2.6-3.6
      hr). Consistent with this, in dogs relatively little O-glucuronide was observed
      in plasma, but in rats and mice the AUCs for glucuronide were greater than the
      parent AUC. A dose-ranging study in rats revealed oral absorption of LY288513 is
      nonsaturated, even after 800 mg/kg oral doses. A plot of AUC vs. dose revealed a
      consistent overproportional increase in AUC for both parent and glucuronide
      metabolite with increasing dose.

PMID- 8565781
TI  - Disposition of the opioid antagonist, LY255582, in rats and dogs.
AB  - LY255582 is a phenylpiperidine opioid antagonist under development as an appetite
      suppressant and for the treatment of obesity. Female beagles were administered
      [14C]LY255582 at dosages of 0.72 mg/kg intravenously or 7.2 mg/kg orally. The
      majority (54-58%) of the radioactivity was eliminated in the urine over 8 days
      after both oral and intravenous drug administration, primarily as polar
      metabolites. Peak plasma levels of parent drug in the dog were 11.5 and 311 ng/ml
      after oral and intravenous administration, respectively, and declined with a half
      life of 3.2 hr. Peak plasma levels of LY255582 in the rat were 7.9 and 160 ng/ml
      after administration of [14C]LY255582 at dosages of 35 mg/kg orally and 1 mg/kg
      intravenously, respectively. The half-life of parent drug in rats was 1.5 hr;
      however, the terminal half-lives of radioactivity equivalents were 7.9 and 31.7
      hr after intravenous and oral administration, respectively. The bioavailability
      of parent LY255582 was < 1% in both the rat and the dog, primarily because of
      extensive first-pass metabolism. Whole-body autoradiographic studies in rats
      after administration of a single oral 35 mg/kg dose of [14C]LY255582 indicated
      that radioactivity was rapidly absorbed and distributed throughout the body.
      Radioactivity concentrated in the liver and was eliminated slowly. Little or no
      parent drug was eliminated in the urine of either species. As in the urine, the
      major residues present in the liver and bile of rats orally administered
      [14C]LY255582 were uncharacterized polar metabolites with little parent drug
      present.

PMID- 8565782
TI  - Induction of rodent hepatic drug-metabolizing enzyme activities by the novel
      anticonvulsant remacemide hydrochloride.
AB  - Remacemide hydrochloride [FPL 12924AA; 2-amino-N-(1-methyl-1,2-diphenylethyl)
      acetamide hydrochloride] is being evaluated as a novel neuroprotective treatment
      for epilepsy and stroke. Preliminary safety evaluation studies in the rat have
      shown that repeated doses of the compound produce histological and biochemical
      changes consistent with hepatic enzyme induction. To examine this further, the
      levels and activities of the major drug metabolizing cytochrome P450 (CYP)
      subfamilies (CPY1, CYP2, and CYP3) were monitored in microsomal samples from male
      Sprague-Dawley rats dosed by gavage with FPL 12924AA (250 mg base.kg-1.day-1 for
      28 days) or an equivalent volume of vehicle (controls). The interpretation of the
      findings was aided by comparison with the effects of phenobarbitone (75 mg.kg
      1.day-1 ip for 4 days) and beta-naphthoflavone (a single intraperitoneal dose at
      80 mg.kg-1.day-1). No significant changes in total hepatic P450 levels (1.44 +/-
      0.40 nmol.mg-1 vs. 1.31 +/- 0.19 nmol.mg-1 in controls) or ethoxyresorufin O
      deethylase activity (a CYP1A induction probe) were observed after remacemide
      treatment. The pattern of induction produced by remacemide was very similar to
      that observed with phenobarbitone. The nonspecific CYP-dependent reaction
      ethoxycoumarin O-deethylation was induced approximately 2-fold. The specific
      CYP2B markers pentoxyresorufin O-depentylase and 16 beta-hydroxytestosterone
      production were both increased markedly by FPL 12924AA (approximately 100- and 20
      fold, respectively). 2 beta- and 6 beta-Hydroxytestosterone production were also
      elevated, indicating the induction of CYP3A1/2. Similar effects on isoform
      selective P450-dependent activities were observed in male and female mice treated
      with remacemide as part of a dose-ranging study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8565783
TI  - Determination of human hepatic cytochrome P4501A2 activity in vitro use of
      tacrine as an isoenzyme-specific probe.
AB  - Oxidative metabolism of the cognition activator tacrine (1,2,3,4-tetrahydro-9
      aminoacridine) is thought to be catalyzed by cytochrome P4501A2 (CYP1A2). In this
      study, the use of tacrine as a specific substrate to measure CYP1A2 activity in
      vitro was investigated. Tacrine metabolism was assessed in 16 human liver
      microsomal samples. Initially, the percentage conversion of tacrine to stable
      metabolites (i.e. 1-, 2-, 4-, and 7-hydroxytacrine) at a single time point was
      correlated with levels of CYP1A2 apoprotein. Apoprotein was detected by
      immunoquantification using a monospecific CYP1A2 antipeptide antibody.
      Significant correlations were seen between CYP1A2 content and the degree of 1
      hydroxylation (r = 0.81, p < 0.001), 7-hydroxylation (r = 0.70, p < 0.001), and
      metabolism to all stable products (r = 0.82, p < 0.001). The major metabolite
      formed in all livers was 1-hydroxytacrine. The conversion of tacrine to this
      metabolite was examined in more detail. The rate of formation varied from 19.2
      pmol min-1 mg-1 to 101.0 pmol min-1 mg-1. There was a significant correlation (r
      = 0.84, p < 0.001) between the rate of formation and CYP1A2 levels. Tacrine
      metabolism was also compared with the rate of formation of 3-methylxanthine, from
      theophylline, a reaction previously shown to be catalyzed by CYP1A2. Significant
      correlations were found between 3-methylxanthine formation and all quantified
      tacrine metabolites. The rate of 3-methylxanthine generation also correlated with
      CYP1A2 apoprotein levels. It is concluded, therefore, that tacrine is a valuable
      probe for the determination of human hepatic CYP1A2 activity in vitro.

PMID- 8565784
TI  - Comparison of purified human and rabbit serum paraoxonases.
AB  - Rabbit serum paraoxonase (PON) activity was reported to be nearly 20 times
      greater than that found for humans and all other mammalian species tested, to
      date. However, 85% of the amino acid residues are identical in human and rabbit
      PONs, and the two purified PONs show similar substrate specificity patterns. Both
      are stimulated by phospholipids and have two asparagine-linked sugar chains. Both
      also have one intramolecular disulfide bond and one free sulfhydryl residue per
      molecule. Both require Ca2+ for stability and for catalytic activity. Zn2+ and
      Cd2+ also stabilize both PONs and prevent irreversible denaturation, but neither
      metal confers catalytic activity. Maximum specific activities for both esterases
      were approximately 2,000 units of arylesterase activity/mg protein. In contrast,
      rabbit PON is more stable than human PON to heat inactivation and sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis treatment. Chelex 100 strips Ca2+ from
      human PON more easily, and EDTA is less inhibitory with rabbit PON. We conclude
      that human and rabbit PONs have very similar active centers, but the latter binds
      Ca2+ more tightly, is a more stable enzyme, and is maintained at 3- to 4-fold
      higher steady-state concentrations in serum than its human counterpart. PON
      activity depends on adequate Ca2+ being available; therefore, apparently much
      higher levels of PON activity in rabbits can be explained by the reduced Ca2+
      concentrations present in the early assay methods.

PMID- 8565785
TI  - Bacterial expression and kinetic characterization of the human monoamine
      sulfating form of phenol sulfotransferase.
AB  - The cDNA for the human monoamine-sulfating form of phenol sulfotransferase (hM
      PST) was isolated from a T47D human breast carcinoma lambda gt10 cDNA library,
      and the active enzyme was expressed in Escherichia coli. Expressed hM-PST was
      very similar to the brain, intestinal, and platelet forms of the enzyme in its
      physical, immunological, and kinetic properties. The ability of hM-PST to sulfate
      a number of xenobiotics was examined and compared with the bacterially expressed
      human phenol-sulfating form of PST (hP-PST). The translation product of the T47D
      hM-PST cDNA was 92% identical to that of liver hP-PST. Monoamine
      neurotransmittors, such as epinephrine and dopamine, were maximally conjugated at
      lower concentrations by expressed hM-PST (2 and 20 microM, respectively) than by
      hP-PST (1 and 1 mM, respectively). In contrast, simple phenols--such as p
      nitrophenol, acetaminophen, and alpha-naphthol--were maximally conjugated at
      lower concentrations (4 microM, 20 microM, and 0.5 microM, respectively) by hP
      PST than by hM-PST (1 mM, 1.5 mM, and 50 microM, respectively). Minoxidil was
      sulfated at similar rates and concentrations (7 mM) by both forms of PST. None of
      the estrogens or related compounds, such as beta-estradiol, 17 alpha
      ethinylestradiol, diethylstilbestrol, equilenin, or genistein tested as
      substrates were sulfated by hM-PST; however, all of these compounds were
      substrates for hP-PST. As with hP-PST, the hydroxysteroids dehydroepiandrosterone
      and cortisol were not sulfated by hM-PST.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8565786
TI  - Application of hyphenated LC/NMR and LC/MS techniques in rapid identification of
      in vitro and in vivo metabolites of iloperidone.
AB  - Iloperidone, 1(-)[4(-)[3(-)[4-(6-fluro-1,2-benzisoxazol-3-yl)-1-
      piperidinyl]propoxy]-3-methoxyphenyl]ethanone, is currently undergoing clinical
      trials as a potential antipsychotic agent. Iloperidone was found to be
      extensively metabolized to a number of metabolites by rats, dogs, and humans.
      LC/MS/MS was used to characterize and identify metabolites of iloperidone present
      in complex biological mixtures obtained from all three species. Identification of
      some of the unknown metabolites in rat bile was achieved successfully by
      combination of LC/NMR and LC/MS with a minimum amount of sample cleanup. The
      utility of coupling a semipreparative HPLC to LC/MS instrument for further
      characterization of collected metabolites was demonstrated. It was shown that
      iloperidone was metabolized by O-dealkylation processes to yield 6-fluoro-3(-)[1
      (3-hydroxypropyl)-4-piperidinyl]-1,2-benzisoxazole and 1(-)[4(-)[3(-)[4-(6-fluoro
      1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]-2-hydroxyphenyl]ethanone.
      Oxidative N-dealkylation led to the formation of 6-fluoro-3-(4-piperidinyl)-1,2
      benzisoxazole and a secondary metabolite, 3(-)[(4-acetyl-2
      methoxy)phenoxy]propionic acid. Iloperidone was reduced to produce 4(-)[3(-)[4-(6
      fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]- propoxy]-3-methoxy-alpha
      methylbenzenemethanol as the major metabolite in humans and rats. Hydroxylation
      of iloperidone produced 1(-)[4(-)[3(-)[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-
      piperidinyl]propoxy]-2-hydroxy-5-methoxyphenyl]ethanone and 1(-)[4(-)[3(-)[4-(6
      fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-3 -methoxyphenyl]propoxy]-2
      hydroxyethanone, the later of which was found to be the principal metabolite in
      dogs. The identities of all these metabolites were established by comparing the
      LC/MS retention times and mass spectral data with synthetic standards.

PMID- 8565787
TI  - Mechanisms of tumor modulation by indole-3-carbinol. Disposition and excretion in
      male Fischer 344 rats.
AB  - This study describes the disposition and excretion of indole-3-carbinol (I3C), a
      natural dietary tumor modulator and candidate chemopreventive agent, in male
      Fisher 344 rats after continuous dietary or a single oral administration. Steady
      state urinary and fecal excretion were attained 40 and 112 hr, respectively,
      after commencing continuous exposure. These two routes accounted for
      approximately 75% of the administered dose, of which 77% appeared in feces. After
      7 days of 2,000 ppm dietary I3C, a mean of 1,154 microM I3C eq was found in
      liver, of which 17% was present as extractable, unbound I3C derivatives. Total
      equivalents in liver decreased to 643 and 411 microM 24 and 48 hr later,
      respectively, for animals returned to control diet. Mean levels of I3C eq in lung
      decreased from 436 to 219 microM, and blood levels decreased from 320 to 208
      microM over the same 48-hr period. After administration of 1 mmol/kg radioinert
      I3C (a comparable daily dose as in the feeding study) for 6 days, animals were
      given 1 mmol/kg [3H]I3C. Mean liver levels were 257, 283, and 541 microM I3C eq
      at 1.5, 3, and 6 hr after dosing, and these levels represented 0.97%, 1.34%, and
      2.45% of the total I3C dose administered, respectively. Concentrations of I3C eq
      changed little in blood, kidney, tongue, or lung over this time period. HPLC
      analysis of ethyl acetate extracts of liver from rats given an oral dose revealed
      24 distinct [3H]I3C-derived peaks. Two of the predominant peaks were identified
      as 3,3'-diindolylmethane (I33', a linear dimer of I3C) and [2-(indol-3-ylmethyl)
      indol-3-yl]indol-3-ylmethane (LT, a linear trimer). A novel I3C metabolite was
      identified as 1-(3-hydroxymethyl)-indolyl-3-indolylmethane (HI-IM). Hepatic
      levels of these metabolites and three major, but unidentified, products were
      between 1.0 and 13.1 microM; highest levels were observed at 6 hr or, for HI-IM,
      at 1.5 hr postdosing. Parent I3C was not detected in liver extracts, whereas the
      potent Ah receptor agonist 3,2-b-indolocarbazole (ICZ) was estimated at 1.6 nM.
      These data suggest that neither I33', LT, or ICZ alone reach sufficient hepatic
      concentration to account for cytochrome P450IA induction by dietary I3C, or
      provide effective inhibition of microsomal bioactivation of the hepatocarcinogen
      aflatoxin B1; however, the total hepatic mixture of I3C derivatives may be
      sufficient to provide both modulatory responses in the rat.

PMID- 8565788
TI  - Investigation of the metabolism of ebrotidine in human urine by liquid
      chromatography-atmospheric pressure chemical ionization mass spectrometry.
AB  - Ebrotidine is a new H2-receptor antagonist that, in addition to its antisecretory
      activity, exhibits a remarkable ability for gastric mucosal protection and acts
      as a potent inhibitor of protease and lipase enzymes elaborated by Helicobacter
      pylori. To study the metabolism of ebrotidine in human urine, HPLC/MS with an
      atmospheric pressure chemical ionization (APCI) interface and simultaneous UV
      detection was conducted. HPLC/MS separation of the reference compounds was
      performed, and positive and negative APCI mass spectra were obtained. Compounds
      of low molecular weight (M(r) < 300) showed predominantly the quasi-molecular
      ion. Intermediate size compounds (300 < M(r) < 400) gave a different type of
      spectra, depending on the ion mode: the positive mass spectra showed only the
      protonated molecular ion, whereas in the negative mass spectra many fragments
      appeared in addition to the deprotonated molecular ion. For molecules with a
      higher molecular weight (M(r) > 400), high fragmentation was observed. LC/MS with
      an APCI interface in positive and negative modes allowed the identification of
      ebrotidine, 4-bromobenzenesulfonamide, and four S-oxidized metabolites in human
      urine.

PMID- 8565789
TI  - Metabolism of [14C]1,3-dinitrobenzene by rat small intestinal mucosa in vitro.
AB  - The small intestine can metabolize a variety of substances and can play a role in
      the presystemic clearance of ingested compounds. Relatively little is known about
      the ability of small intestine to catalyze the presystemic reductive metabolism
      of xenobiotics. 1,3-Dinitrobenzene (1,3-DNB), which is known to undergo reductive
      biotransformation in an intact, oxygenated isolated perfused intestinal
      preparation, was used as a model substrate for reductive enzymes of the small
      intestine of the rat. Subcellular fractions from duodenal, jejunal, and ileal
      regions of rat small intestinal mucosa were used to characterize the enzyme
      source(s) of those reductive reactions of 1,3-DNB that are relevant in the
      oxygenated intestinal tissue. 1,3-DNB was reduced to 3-nitroaniline (3-NA) by
      cytosol from duodenum and jejunum. The rate of reduction was 2 times faster when
      incubations contained duodenal rather than jejunal cytosol. Jejunal cytosol
      catalyzed reduction of 1,3-DNB was supported by hypoxanthine, NADPH, or NADH.
      Duodenal microsomes catalyzed the reduction of 1,3-DNB to 3-NA in the presence of
      supplemental NADPH or NADH; however, the reaction was very slow. Jejunal
      microsomes, ileal microsomes, and ileal cytosol failed to catalyze the reduction
      of 1,3-DNB. Studies with chemical inhibitors suggested possible roles for DT
      diaphorase, glutathione reductase, or xanthine oxidase in the jejunal cytosol
      catalyzed reaction. Purified, commercially available xanthine oxidase (from
      buttermilk) catalyzed the reduction of 1,3-DNB to 3-NA when supplemented with
      NADH or hypoxanthine.

PMID- 8565790
TI  - Urinary excretion of cicletanine in the rat. Stereochemical aspects.
AB  - The metabolism of (+)-cicletanine and (-)-cicletanine (10 mg kg-1) was studied in
      healthy male Wistar rats 24 hr after a single dose and following daily oral
      administration for 25 days. Urine, collected in 24-hr intervals on days 1, 5, 10,
      15, 20, and 25, was analyzed by an HPLC method for parent drug and its
      sulfate/glucuronide conjugates. In urine, the sulfate and glucuronide conjugates
      of cicletanine were the only two major components quantitated; parent drug was a
      minor component. Within 24 hr after the first dose of (+)-cicletanine, the
      sulfate conjugate was the major urinary component; the ratio of sulfate to
      glucuronide conjugate was 3. After oral administration of (-)-cicletanine, the
      glucuronide and sulfate conjugates were present in similar amounts. For each
      enantiomer, the ratio of sulfate/glucuronide did not change upon multiple dosing,
      and inversion of the enantiomers did not occur. Although sulfate and glucuronide
      conjugates of each enantiomer are formed, the relative amounts of each conjugate
      depends on the enantiomer, indicating that there is stereospecificity in the
      disposition of cicletanine.

PMID- 8565791
TI  - Acidic metabolites of tamoxifen. Aspects of formation and fate in the female rat.
AB  - The nonsteroidal antiestrogen tamoxifen (TAM) is subject to extensive
      biotransformation in humans and laboratory animals. In particular, the
      dimethylamino group of TAM undergoes N-demethylation and formal replacement with
      a hydroxyl group, affording major metabolites TAM amine and TAM alcohol,
      respectively. In the present study in ovariectomized rats, TAM was eliminated in
      part as metabolites arising from conversion of its basic side chain to an
      oxyacetic acid moiety. Thus, TAM acid (TA) was characterized spectrally from the
      urine of rats after intraperitoneal administration of TAM. TA was not detected in
      fecal extracts. In contrast, a second metabolite, 4-hydroxy TA (4HTA), was
      detected and characterized only from fecal extracts, indicative of a qualitative
      difference in routes of elimination for TA and 4HTA. Studies with rat liver
      fractions suggested TAM alcohol to be an intermediate metabolite in the
      conversion of TAM to TA and 4HTA. In liver microsomal fraction, TAM alcohol was
      converted to a novel metabolite, TAM aldehyde, which was isolated and
      characterized as its semicarbazone derivative. Coenzyme requirements for
      formation of this (derivative) metabolite, as well as for conversion of TA to
      4HTA, indicated these transformations to be catalyzed by cytochromes P450. TAM
      aldehyde was shown to be a plausible intermediate in the formation of acidic
      metabolites by experiments that indicated oxidation of this to TA was catalyzed
      by aldehyde oxidase derived from liver cytosolic fraction.

PMID- 8565792
TI  - Inhibition and induction of cytochrome P450 isozymes after repetitive
      administration of imipramine in rats.
AB  - Repetitive oral administration of imipramine (100 mg/kg/day for 5 days) caused a
      decrease in rat liver microsomal debrisoquine 4-hydroxylase activity, a
      characteristic reaction catalyzed by cytochrome P450 (CYP) 2D1. Other CYP2D
      dependent reactions (such as bunitrolol 4-hydroxylation, lidocaine 3
      hydroxylation, and propranolol 4-, 5- and 7-hydroxylations) were also impaired by
      the treatment, but not those catalyzed by other CYP isozymes. Imipramine
      pretreatment did not change the immunochemically determined content of the CYP2D
      protein, suggesting that CYP2D is inactivated. Imipramine pretreatment also
      resulted in an increase in total CYP content and in formation of a ferrous CYP
      metabolic intermediate (MI)-complex absorbing at 454 nm. Although the total CYP
      content was increased by the treatment of these microsomes with ferricyanide to
      dissociate the MI-complex, the CYP2D-dependent activities were not restored,
      suggesting that the MI-complex was not the primary cause of CYP2D inhibition.
      This pretreatment regimen caused marked increases in immunochemically determined
      levels of CYP2A1, CYP2B1, CYP2B2, CYP2C6, and CYP3A2, and in the activities of 2
      alpha-, 2 beta-, 6 beta-, 7 alpha-, 16 alpha-, and 16 beta-hydroxylation and 17
      oxidation of testosterone. These results indicate that imipramine has two actions
      on the liver CYP system (i.e. as an inhibitor of the CYP2D enzyme and as a
      phenobarbital-type inducer).

PMID- 8565793
TI  - The treatment of alcoholism in France.
AB  - Despite a recent decline in per capita alcohol consumption, alcoholism remains a
      serious public health problem in France. Pharmacotherapy is used to make
      withdrawal from alcohol easier and to help maintain abstinence. The recent
      development of effective pharmacologic treatments for alcoholism has increased
      interest in this approach to therapy. To determine the most appropriate form of
      pharmacotherapy for treating alcohol dependence, a meta-analysis of randomized
      controlled studies published between 1960 and 1993 was performed. We found that
      several pharmacotherapeutic agents had demonstrated safety and efficacy on
      different periods of follow-up, including acamprosate (long term), naltrexone
      (intermediate term), fluoxetine and citalopram (short term). Studies of
      zimeldine, nialamide, L-dopa, viloxazine, and tetrabamate failed to demonstrate
      efficacy for these agents in the treatment of alcoholism. Results were ambiguous
      or mixed for lithium, phenytoin, bromocriptine, apomorphine, and buspirone.
      Continued research is needed to identify the most appropriate patients to receive
      treatment with specific forms of pharmacotherapy.

PMID- 8565794
TI  - Innovative perspectives on strategies to develop effective alcoholism treatment
      programs.

PMID- 8565795
TI  - Current strategies for the treatment of alcohol dependence in the United States.
AB  - Substantial progress has been reported in the treatment of patients with
      alcoholism in the United States. Studies that seek to identify the most
      appropriate form of therapy for alcohol-dependent patients have been an important
      part of this effort. Recognition that psychotherapy alone cannot help all
      patients who have alcoholism has led to interest in the use of pharmacotherapy.
      Recent research demonstrates that pharmacotherapy with the opioid receptor
      antagonists naltrexone and nalmefene helps prevent relapse in many alcohol
      dependent patients.

PMID- 8565796
TI  - Pharmacotherapy and psychotherapy for the treatment of alcoholism in Germany.
AB  - Although past alcoholism treatment in Germany has primarily focused on
      psychotherapy, new advances in pharmacotherapy are expanding therapeutic options.
      Recent biomedical studies have produced new theories about how alcohol affects
      neurotransmitters in the brain. These studies have led to new pharmacologic
      strategies for the treatment of alcoholism using dopamine agonists and
      antagonists, serotoninergic agents, glutamate antagonists, and opiate
      antagonists. While preliminary studies of these agents offer encouraging results,
      it remains to be demonstrated which agent(s) will provide effective
      pharmacotherapy for this disease.

PMID- 8565797
TI  - [Clinical research].

PMID- 8565798
TI  - [A new antiviral substance against AIDS is already tested by phase II trial].

PMID- 8565799
TI  - [Behcet disease with primary involvement of the cerebral vessels].
AB  - HISTORY AND CLINICAL FINDINGS: Two months after the onset of mainly frontal
      headaches a 25-year-old man of Turkish descent additionally developed double
      vision. Fundoscopy revealed bilateral choked discs and right trochlear paralysis.
      Computed tomography and digital subtraction angiography demonstrated thrombosis
      of the superior sagittal sinus. On admission to hospital the patient was fully
      conscious but had marked meningism, bilaterally positive Lasegue's sign (painful
      straight leg raising) at a 50 degree angle, and multiple oral aphthous ulcers.
      The sinus thrombosis suggested a chronic inflammatory process, while the oral
      ulcers pointed to Behcet's syndrome. INVESTIGATIONS: Inflammatory parameters
      (erythrocyte sedimentation rate, C-reactive protein and white blood cell count)
      were increased and the HLA-B27 test was positive. Other laboratory tests,
      cerebrospinal fluid, chest radiogram and ECG were unremarkable. TREATMENT AND
      COURSE: Despite intravenous administration of heparin nad cefuroxim for one week
      the sagittal sinus thrombosis spread to the straight sinus. In the third week
      scrotal ulcerations were noted and taken to confirm Behcet's syndrome.
      Immunosuppressive treatment with methylprednisolone (initially 80 mg daily) and 2
      weeks later together with chlorambucil (0.1 mg/kg daily) was started. Four weeks
      later the patient was free of symptoms and discharged. CONCLUSION: Neurological
      signs are not adequately stressed by the International Study Group for Behcet's
      Disease among its listed diagnostic criteria.

PMID- 8565800
TI  - [The differential diagnosis of tumors of the nipple and areola].

PMID- 8565801
TI  - [The treatment of prolactinomas during pregnancy and the lactation period].

PMID- 8565802
TI  - [Ulcer healing through the elimination of Helicobacter pylori: is a week of
      therapy enough?].
AB  - AIM OF STUDY: To test whether one week's triple therapy with omeprazole and two
      antibiotics is enough to induce healing of a peptic (gastric and/or duodenal)
      ulcer. PATIENTS AND METHODS: 112 Patients (73 males, 39 females; median age 55
      [18-88] years) proven by culture or histology to have an Helicobacter (H.) pylori
      infection and uncomplicated peptic (gastroduodenal) ulcer. For one week they
      received omeprazole (20 mg once or twice daily) plus two antibiotics
      (clarithromycin/metronidazole, clarithromycin/tetracycline,
      clarithromycin/amoxycillin or amoxycillin/metronidazole) to eradicate H. pylori.
      No further anti-ulcer treatment was given subsequently. Healing of the ulcer and
      H. pylori status were checked by the urease test, culture and histology
      (endoscopic biopsy) 4 weeks later. RESULTS: The 5-week ulcer healing rate was
      94.6% (95% confidence interval: 89-98%). Persisting ulcers (n = 6) were
      associated with either treatment with aspirin or nonsteroidal antiinflammatory
      drugs (n = 3), persistent H. pylori infection (n = 2) or persistent H. pylori
      infection plus treatment with aspirin (n = 1). The ulcer healing rate was
      significantly higher in patients with eradicated infection than in those with
      posttherapy persistence of H. pylori (97.0 vs. 76.9%; P = 0.02). There were no
      significant differences after 5 weeks between patients with duodenal and those
      with gastric ulcer (97.4 vs. 89.3%). CONCLUSIONS: One-week effective eradication
      treatment is adequate to induce healing of H. pylori-positive peptic ulcers. Anti
      ulcer treatment after eradication of H. pylori should be considered only if the
      patient is receiving treatment with ulcerogenic drugs or continues to have
      symptoms.

PMID- 8565803
TI  - [Tamoxifen in male infertility. Analysis of a questionable therapy].

PMID- 8565804
TI  - [Fluoride tablets for caries prevention in children with neurodermatitis and
      cow's milk allergy?].

PMID- 8565805
TI  - [Allergic contact dermatitis due to propantheline bromide].

PMID- 8565806
TI  - [Mesalazine].

PMID- 8565807
TI  - [Thromboendarterectomy in chronic thromboembolic pulmonary hypertension.
      Hemodynamics and right-heart function over the long term].
AB  - OBJECTIVE: To find out whether pulmonary thromboendarterectomy (PTE) can achieve
      lasting reduction of pulmonary vascular resistance in patients with pulmonary
      arterial hypertension due to chronic thromboembolism. PATIENTS AND METHODS: 45
      patients (25 women, 20 men; mean age 45 +/- 24 [19-67] years) were re
      investigated a mean of 21 (13-32) months after successful PTE. Two patients had
      then been in New York Heart Association (NYHA) stage II, 26 in stage III, and 17
      in stage IV. In addition to clinical examination and chest radiogram 36 patients
      had right heart catheterization, 28 pulmonary angiography and 44
      echocardiography. RESULTS: Definite improvement of symptoms had occurred in all.
      34 were now in NYHA stage I, nine in stage II, and two in stage III. The
      pulmonary vascular resistance was significantly lower than before and immediately
      after PTE (pre-PTE: 1052 +/- 472 dyn.s.cm-5; post-PTE: 293 +/- 175 dyn.s.cm-5; at
      follow-up: 187 +/- 92 dyn.s.cm-5; P < 0.001 for follow-up vs pre-PTE; P < 0.05
      for follow-up vs post-PTE). Correspondingly, cardiac index had significantly
      increased (3.0 +/- 0.5 vs 2.0 +/- 0.7 l/min.m2; P < 0.001). Radiological and
      echocardiographic examinations showed a definite decrease in right ventricular
      dimensions and improvement in right ventricular function. CONCLUSION: In patients
      with pulmonary arterial hypertension due to chronic pulmonary thromboembolism PTE
      can achieve a reduction in pulmonary vascular resistance with lasting improvement
      in right heart function and clinical symptoms.

PMID- 8565808
TI  - [The Society of German Naturalists and Physicians: the traditional alliance of
      natural science and medicine].

PMID- 8565809
TI  - [Implantable catheter systems. Experiences with 1000 patients with central venous
      ports].
AB  - OBJECTIVE: To assess retrospectively duration of functioning and rate of
      complications of a totally implantable venous access system used for long-term
      chemotherapy. PATIENTS AND METHODS: Between 1985 and 1993, a central venous
      access system (Port-a-Cath) had been implanted subcutaneously for long-term
      chemotherapy in 1000 patients (479 males, 521 females; mean age 49 [15-86]
      years). Follow-up observations lasted until the end of the chemotherapy or the
      removal of the system. RESULTS: Mean time of functioning of the catheter system
      was 284 (2-1563) days. The complication rate was 12.8%: catheter infection in
      4.9% and catheter thrombosis in 3.2%. A further 4.7% of patients had less common
      complications (malfunction, catheter dislocation, skin necrosis, catheter break
      or disconnection, pneumothorax). A total of 119 (11.9%) systems had to be removed
      because of complications. The rates of infection and of other complications were
      significantly lower in patients with solid tumours (2 and 4%, respectively) than
      in those with haematological disease (6 and 8%) (P < 0.05 for each). CONCLUSION:
      Totally implantable venous access systems are suitable for long-term chemotherapy
      and cause few complications.

PMID- 8565810
TI  - [Duplex sonographic studies on the pathogenesis of splenic hemodynamics in liver
      cirrhosis].
AB  - AIM OF STUDY: The haemodynamic role of the spleen in portal hypertension remains
      unclear. Duplex sonography was undertaken prospectively to discover the
      relationship of splenomegaly and splenic vein flow to type and severity of liver
      cirrhosis and portal vein flow, as well as to the degree of oesophageal varices.
      PATIENTS AND METHODS: 89 patients (54 men, 35 women; mean age 52 [26-81] years),
      diagnosed in the second half of 1993 as having liver cirrhosis were consecutively
      included in the study. In 40 patients the cirrhosis was in stage A (according to
      Child-Pugh classification), in 31 in stage B and in 18 in stage C. RESULTS:
      Portal vein flow fell significantly with increasing degree of cirrhosis (stage A:
      8.29 cm/s; stage B 7.03 cm/s; stage C 5.26 cm/s; P < 0.05). Splenic vein flow
      differed significantly only between stages B and C (stage A: 9.22 cm/s; stage B:
      9.46 cm/s; stage C: 7.87 cm/s; B vs C, P < 0.05). There was no correlation
      between portal vein flow, splenic vein flow, degree of splenomegaly and extent of
      oesophageal varices. CONCLUSION: The results may be explained by the presence of
      collateral circulations and by the differing pathophysiological part played by
      the spleen in liver cirrhosis of different aetiologies.

PMID- 8565811
TI  - [Implantation metastases following laparoscopic cholecystectomy in gallbladder
      carcinoma].
AB  - HISTORY AND CLINICAL FINDINGS: A 66-year-old woman was known to have had
      cholecystolithiasis for at least 4 years. Laparoscopic cholecystectomy was
      performed at another hospital where histological examination surprisingly
      revealed middle-grade differentiated carcinoma of the gall-bladder (pT2, G2). A
      nodular metastasis of the gall-bladder carcinoma was noted on the abdominal wall
      3 months later and excised. Lymph-vessel carcinomatosis was already present. The
      patient again noticed a tumour in the right mid-abdomen and a further tumour was
      palpated in the epigastrium 5 months after the operation. INVESTIGATIONS:
      Laboratory and tumour-marker (CEA, CA 19-9) tests were unremarkable, while
      sonography and computed tomography were highly suspicious for abdominal wall
      metastases in the epigastrium and right mid-abdomen. TREATMENT AND COURSE: Both
      metastases were excised. Laparotomy revealed tumour recurrence in the old gall
      bladder bed, as well as extensive peritoneal carcinoma. Two months after the
      operation she developed jaundice, caused by tumour compression of the choledochal
      duct. An expanding stent was inserted into the stenosed section of the duct. The
      patient died 13 months after the first operation from the underlying malignancy
      with multiple liver metastases and malignant ascites. CONCLUSIONS: Indications
      for minimally invasive surgery in malignant tumour should be narrowly defined.
      Because tumour seeding is possible after laparoscopic cholecystectomy with
      incidentally found carcinoma extensive re-excision should be performed.

PMID- 8565812
TI  - [Bartonella (Rochalimaea) infections: cat-scratch disease and bacillary
      angiomatosis].

PMID- 8565813
TI  - [Diastolic dysfunction of the heart. A frequently overlooked cause of chronic
      heart failure].

PMID- 8565814
TI  - [What influence should clinical studies have on the physician's practice?
      Reflections on the example of acute dialysis].

PMID- 8565815
TI  - [Should lipid-lowering agents be prescribed in myasthenia?].

PMID- 8565816
TI  - [ACE inhibitor-associated interstitial lung infiltrates].

PMID- 8565817
TI  - asense is a Drosophila neural precursor gene and is capable of initiating sense
      organ formation.
AB  - Neural precursor cells in Drosophila arise from the ectoderm in the embryo and
      from imaginal disc epithelia in the larva. In both cases, this process requires
      daughterless and the proneural genes achaete, scute and lethal-of-scute of the
      achaete-scute complex. These genes encode basic helix-loop-helix proteins, which
      are nuclear transcription factors, as does the asense gene of the achaete-scute
      complex. Our studies suggest that asense is a neural precursor gene, rather than
      a proneural gene. Unlike the proneural achaete-scute gene products, the asense
      RNA and protein are found in the neural precursor during its formation, but not
      in the proneural cluster of cells that gives rise to the neural precursor cell.
      Also, asense expression persists longer during neural precursor development than
      the proneural gene products; it is still expressed after the first division of
      the neural precursor. Moreover, asense is likely to be downstream of the
      proneural genes, because (1) asense expression is affected in proneural and
      neurogenic mutant backgrounds, (2) ectopic  expression of asense protein with an
      intact DNA-binding domain bypasses the requirement for achaete and scute in the
      formation of imaginal sense organs. We further note that asense ectopic
      expression is capable of initiating the sense organ fate in cells that do not
      normally require the action of asense. Our studies therefore serve as a
      cautionary note for the inference of normal gene function based on the gain-of
      function phenotype after ectopic expression.

PMID- 8565818
TI  - Induction of terminal differentiation of Dictyostelium by cAMP-dependent protein
      kinase and opposing effects of intracellulr and extracellular cAMP on stalk cell
      differentiation.
AB  - Expression of the catalytic (C) subunit of the cAMP-dependent protein kinase
      (PKA) of Dictyostelium under the control of heterologous, cell-type-specific
      promoters causes ectopic terminal differentiation. When expressed under the
      control of a prespore-specific promoter, development is accelerated, to yield
      highly aberrant fruiting bodies that contain a basal mass of spore cells
      surrounding a central stalk-like structure. When expressed under the control of a
      prestalk-specific promoter, development arrests much earlier, at the tight mound
      stage. Prestalk cells move to the apices of these mounds, apparently normally,
      but no tip is formed. Most of the prestalk cells remain arrested in their
      development but there are a few isolated stalk cells scattered within such
      mounds. We show that extracellular cAMP represses stalk cell-specific gene
      expression in cells where the kinase is constitutively active, suggesting that
      inhibition of stalk cell differentiation by cAMP in normal cells (Berks and Kay,
      1988) occurs because of an effect of extracellular cAMP on an intracellular
      signalling pathway independent of PKA. We propose a scheme whereby two separate
      events, a rise in intracellular cAMP levels and a fall in extracellular cAMP
      concentration, are required to induce stalk cell differentiation.

PMID- 8565819
TI  - The regulation and function of the helix-loop-helix gene, asense, in Drosophila
      neural precursors.
AB  - asense is a member of the achaete-scute complex (AS-C) of helix-loop-helix genes
      involved in Drosophila neurogenesis. Unlike the other AS-C members, which are
      expressed in subsets of the ectodermal areas (proneural clusters) that give rise
      to neural precursors, asense is one of a number of genes that are specifically
      expressed in the neural precursors themselves (neural precursor genes). We have
      identified a mutant asense phenotype that may reflect this later expression
      pattern. As a step in understanding the determination of neural precursors from
      the proneural clusters, we have investigated the potential role of the AS-C
      products as direct transcriptional activators of neural precursor genes by
      analysing the regulation of asense. Using genomic rescues and asense-lacZ fusion
      genes, the neural precursor regulatory element has been identified. We show that
      this element contains binding sites for AS-C/daughterless heterodimers. Delection
      of these sites reduces the expression from the fusion gene, but significant
      expression is still achieved, pointing to the existence of other regulators of
      asense in addition to the AS-C. asense differs from the other AS-C members in its
      expression pattern, regulation, mutant phenotype and some DNA-binding
      properities.

PMID- 8565820
TI  - Programmed cell death in the absence of c-Fos and c-Jun.
AB  - Programmed cell death, or apoptosis, is a normal process in the development of a
      variety of embryonic and adult tissues, and is also observed in several
      pathological conditions. Several recent studies, using both expression and
      functional assays, have implicated the transcription factor, AP-1, in the
      regulation of programmed cell death, and specifically implicate the genes c-fos
      and c-jun, as well as some other family members. If the products of the c-fos
      and/or c-jun genes are essential components in the cascade of events that leads
      to programmed cell death in mammalian cells, it follows that cell death would not
      occur in mice lacking functional copies of these genes. We have made use of null
      mutations in the c-fos and c-jun genes that were produced by gene targeting
      (Johnson, R.S., Spiegelman, B.M. and Papaioannou, V.E. (1992). Cell 71, 577-586;
      Johnson, R.S., Van Lingen, B., Papaioannou, V.E. and Spiegelman, B.M. (1993).
      Genes Dev. 7, 1309-1317) to investigate this possibility. Cell death was assayed
      using an in situ apoptosis assay in c-fos null embryos and adults, c-jun null
      embryos, and c-fos/c-jun double null embryos compared with control mice. The
      occurrence of cell death in c-fos null mice was also assessed in two experimental
      conditions that normally lead to neuronal cell death. The first was unilateral
      section of the sciatic nerve in neonates, which leads to the death of anterior
      horn cells of the spinal cord on the operated side. The second was a genetic
      cross combining the weaver mutation, which causes death of cerebellar granule
      cells, with the c-fos mutation. Our results show that programmed cell death
      occurs normally in developing embryonic tissues and adult thymus and ovary,
      regardless of the absence of a functional c-fos gene. Furthermore, absence of c
      fos had no effect on neuronal cell death in the spinal cord following sciatic
      nerve section, or in heterozygous weavers' cerebellae. Finally, the results show
      that programmed cell death can take place in embryos lacking both Fos and Jun.

PMID- 8565821
TI  - The Arabidopsis homeotic genes APETALA3 and PISTILLATA are sufficient to provide
      the B class organ identity function.
AB  - The class B organ identity genes, APETALA3 and PISTILLATA, are required to
      specify petal and stamen identity in the Arabidopsis flower. We show here that
      the activities of these two genes are sufficient to specify petals and stamens in
      flowers, in combination with the class A and C genes, respectively. Flowers of
      plants constitutively expressing both PISTILLATA and APETALA3 under the control
      of the 35S promoter from cauliflower mosaic virus consist of two outer whorls of
      petals and inner whorls of stamens. These plants also exhibit vegetative
      phenotypes that are not present in either of the singly (APETALA3 or PISTILLATA)
      overexpressing lines. These phenotypes include leaf curling and the partial
      conversion of later-arising cauline leaves to petals. The presence of additional
      floral whorls in flowers ectopically expressing APETALA3 and PISTILLATA and the
      rescue of missing organs in class A mutants by ectopic B function suggest that
      APETALA3 and PISTILLATA play an additional role in proliferation of the floral
      meristem.

PMID- 8565822
TI  - Defective bone formation in Krox-20 mutant mice.
AB  - Endochondral ossification is the prevalent mode of vertebrate skeleton formation;
      it starts during embryogenesis when cartilage models of long bones develop
      central regions of hypertrophy which are replaced by bony trabeculae and bone
      marrow. Although several transcription factors have been implicated in pattern
      formation in the limbs and axial skeleton, little is known about the
      transcriptional regulations involved in bone formation. We have created a null
      allele in the mouse Krox-20 gene, which encodes a zinc finger transcription
      factor, by in frame insertion of the E. coli lacZ gene and shown that hindbrain
      segmentation and peripheral nerve myelination are affected in Krox-20-/- embryos.
      We report here that Krox-20 is also activated in a subpopulation of growth plate
      hypertrophic chondrocytes and in differentiating osteoblasts and that its
      disruption severely affects endochondral ossification. Krox-20-/- mice develop
      skeletal abnormalities including a reduced length and thickness of newly formed
      bones, a drastic reduction of calcified trabeculae and severe porosity. The
      periosteal component to bone formation and calcification does not appear to be
      affected in the homozygous mutant suggesting that the major role for Krox-20 is
      to be found in the control of the hypertrophic chondrocyte-osteoblast
      interactions leading to endosteal bone formation.

PMID- 8565823
TI  - Apoptosis in the developing tooth: association with an embryonic signaling center
      and suppression by EGF and FGF-4.
AB  - Apoptosis was localized in developing mouse teeth from initiation of
      morphogenesis to completion of cusp formation by using modified TUNEL method for
      serial sections and Nile Blue staining for whole mounts. Apoptosis was first
      detected at bud stage (E12-E13) in the central cells of the invaginating dental
      epithelium suggesting involvement of cell death in epithelial budding
      morphogenesis. During cusp development, apoptotic cells were located in the
      enamel knots, which are transient clusters of dental epithelial cells proposed to
      act as signaling centers directing the morphogenesis of tooth cusps. Apoptosis
      was also detected in other restricted epithelial cell populations including the
      dental lamina, ameloblasts, as well as stratum intermedium and stellate reticulum
      cells suggesting that the removal of these epithelial cells occurs by apoptosis.
      Apoptotic cells, presumably osteoclasts, were also located on the surfaces of the
      developing alveolar bone. When dissected E13 dental epithelium or mesenchyme were
      cultured in isolation, apoptotic cells were abundant throughout the tissues,
      whereas when cultured together, apoptosis was inhibited in both tissues close to
      their interface indicating that epithelial-mesenchymal tissue interactions
      prevent apoptosis. Epidermal growth factor (EGF) and fibroblast growth factor-4
      (FGF-4) inhibited apoptosis in the dental mesenchyme when applied locally using
      agarose or heparin-coated acrylic beads, suggesting involvement of these or
      related growth factors in the prevention of apoptosis in dental tissues in vivo.
      The spatially and temporally restricted distribution patterns of apoptotic cells
      suggest multiple roles for programmed cell death in dental development. Of
      particular interest is the removal of the enamel knots by apoptosis which may
      terminate their tasks as regulators of the patterning of the tooth cusps. The
      apical ectodermal ridge (AER) of the limb bud has similar signaling
      characteristics as the enamel knot, and it also undergoes apoptosis. Hence,
      apoptosis may be a general mechanism for the silencing of embryonic signaling
      centers.

PMID- 8565824
TI  - Glide directs glial fate commitment and cell fate switch between neurones and
      glia.
AB  - Glial cells constitute the second component of the nervous system and are
      important during neuronal development. In this paper we describe a gene, glial
      cell deficient, (glide), that is necessary for glial cell fate commitment in
      Drosophila melanogaster. Mutations at the glide locus prevent glial cell
      determination in the embryonic central and peripheral nervous system. Moreover,
      we show that the absence of glial cells is the consequence of a cell fate switch
      from glia to neurones. This suggests the existence of a multipotent precursor
      cells in the nervous system. glide mutants also display defects in axonal
      navigation, which confirms and extends previous results indicating a role for
      glial cells in these processes.

PMID- 8565825
TI  - Alterations in somite patterning of Myf-5-deficient mice: a possible role for FGF
      4 and FGF-6.
AB  - Mice carrying a targeted mutation in the gene for the myogenic factor Myf-5 fail
      to form major parts of the ribs, which leads to an unstable thorax and perinatal
      death. Here, we report that somites of Myf-5-deficient mice lack the expression
      of FGF-4 and FGF-6 while TGF beta-2 is expressed normally. Early sclerotomal
      markers, such as Pax-1 reveal no substantial reduction of sclerotome size. At
      E11.5 the condensing mesenchyme of the rib anlagen is considerably reduced in
      size in Myf-5 mutant mice. This may be caused by the lack of Myf-5-positive, FGF
      expressing cells which normally are in close contact with the lateral sclerotome
      generating the rib progenitors. The potential role of FGFs and TGF beta on
      sclerotome formation is demonstrated in micromass cultures of early somites.
      Combinations of FGF-4 or FGF-6 with TGF beta-2 potentiate chondrogenesis
      suggesting that these growth factors emanating from early myotomal and
      dermomyotomal cells may have instructive or permissive effects on differentiation
      or outgrowth of sclerotomal cells.

PMID- 8565826
TI  - Anterior pituitary cells defective in the cell-autonomous factor, df, undergo
      cell lineage specification but not expansion.
AB  - The Ames dwarf mouse transmits a recessive mutation (df) resulting in a profound
      anterior pituitary hypocellularity due to a general lack of thyrotropes,
      somatotropes and lactotropes. These cell types are also dependent on the
      pituitary-specific transcription factor, Pit-1. We present evidence that
      expression of Pit-1 and limited commitment to these cells lineages occurs in
      df/df pituitaries. Thus, the crucial role of df may be in lineage-specific
      proliferation, rather than cytodifferentiation. The presence of all three Pit-1
      dependent cell types in clonally derived clusters provides compelling evidence
      that these three lineages share a common, pluripotent precursor cell. Clusters
      containing different combinations of Pit-1-dependent cell types suggests that the
      Pit-1+ precursor cells choose from multiple developmental options during
      ontogeny. Characterization of df/df<-->+/+ chimeric mice demonstrated that df
      functions by a cell-autonomous mechanism. Therefore, df and Pit-1 are both cell
      autonomous factors required for thyrotrope, somatotrope and lactotrope ontogeny,
      but their relative roles are different.

PMID- 8565827
TI  - Genes of the Enhancer of split and achaete-scute complexes are required for a
      regulatory loop between Notch and Delta during lateral signalling in Drosophila.
AB  - Like the neuroblasts of the central nervous system, sensory organ precursors of
      the peripheral nervous system of the Drosophila thorax arise as single spaced
      cells. However, groups of cells initially have neural potential as visualized by
      the expression of the proneural genes achaete and scute. A class of genes, known
      as the 'neurogenic genes', function to restrict the proportion of cells that
      differentiate as sensory organ precursors. They mediate cell communication
      between the competent cells by means of an inhibitory signal, Delta, that is
      transduced through the Notch receptor and results in a cessation of achaete-scute
      activity. Here we show that mutation of either the bHLH-encoding genes of the
      Enhancer of split complex (E(spl)-C) or groucho, like Notch or Delta mutants,
      cause an overproduction of sensory organ precursors at the expense of epidermis.
      The mutant cells behave antonomously suggesting that the corresponding gene
      products are required for reception of the inhibitory signal. Epistasis
      experiments place both E(spl)-C bHLH-encoding genes and groucho downstream of
      Notch and upstream of achaete and scute, consistent with the idea that they are
      part of the Notch signalling cascade. Since all competent cells produce both the
      receptor and its ligand, it was postulated that Notch and Delta are linked within
      each cell by a feedback loop. We show, that, like mutant Notch cells, cells
      mutant for E(spl)-C bHLH-encoding genes or groucho inhibit neighbouring wild-type
      cells causing them to adopt the epidermal fate. This inhibition requires the
      genes of the achaete-scute complex (AS-C) which must therefore regulate the
      signal Delta. Thus there is a regulatory loop between Notch and Delta that is
      under the transcriptional control of the E(spl)-C and AS-C genes.

PMID- 8565828
TI  - Development of the mammalian ear: coordinate regulation of formation of the
      tympanic ring and the external acoustic meatus.
AB  - The tympanic membrane in mammals is a trilaminar structure formed by the
      apposition of two epithelial cell layers, along with an intervening layer of
      cells derived from pharyngeal arch mesenchyme. One epithelial layer is
      contributed by the external acoustic meatus, a derivative of the first pharyngeal
      cleft. The other epithelial layer is contributed by the tubotympanic recess, a
      derivative of the first pharyngeal pouch. We demonstrate here an absolute
      correlation between formation of the external acoustic meatus and formation of
      the tympanic ring, a first arch-derived membrane bone that anchors the tympanic
      membrane. Experimental loss of the tympanic ring by retinoic acid treatment, or
      duplication of the ring in Hoxa-2 null mutant embryos, resulted in corresponding
      alterations in formation of the external acoustic meatus. We suggest that the
      tympanic ring primordium induces formation and morphogenesis of the external
      acoustic meatus, and that expression of the Hoxa-2 and goosecoid genes may be
      involved in regulating the formation and morphogenesis of these structures.

PMID- 8565830
TI  - Retinoic acid establishes ventral retinal characteristics.
AB  - The developing eye is known to be rich in retinoic acid (RA), and perturbations
      in RA levels during formation of the optic primordia, as well as RA receptor
      mutations, cause retinal malformations, especially in ventral eye regions. To
      test the hypothesis that RA plays a role in the establishment of ventral retinal
      characteristics, we examined several dorsal and ventral ocular markers in RA
      treated zebrafish. The optic stalk represents the ventral-most region of the
      early eye field. During normal development, the optic stalks constrict,
      decreasing in width and are gradually replaced by the optic nerve. Systemic high
      RA levels cause an expansion in the optic stalk with an increased cell content
      and a patent lumen. In addition, the stalks do not constrict and persist into
      later stages of development indicating an enhancement of early ventral eye
      characteristics. Expression of the transcription factor pax[b], normally confined
      to the ventral retina, expands into the dorsal retina following RA treatment,
      whereas msh[c], normally expressed in the dorsal retinal pole, disappears.
      Activity of an aldehyde dehydrogenase that normally occupies the dorsal third of
      the retina is reduced or abolished following high systemic RA. When a localized
      RA source, an RA-soaked bead, is placed next to the developing eye, a fissure
      resembling the choroid fissure appears in the eye facing the bead. Taken
      together, these observations suggest that RA is involved in the determination of
      the ventral retina.

PMID- 8565829
TI  - Two distinct phases of apoptosis in mammary gland involution: proteinase
      independent and -dependent pathways.
AB  - Postlactational involution of the mammary gland is characterized by two distinct
      physiological events: apoptosis of the secretory, epithelial cells undergoing
      programmed cell death, and proteolytic degradation of the mammary gland basement
      membrane. We examined the spatial and temporal patterns of apoptotic cells in
      relation to those of proteinases during involution of the BALB/c mouse mammary
      gland. Apoptosis was almost absent during lactation but became evident at day 2
      of involution, when beta-casein gene expression was still high. Apoptotic cells
      were then seen at least up to day 8 of involution, when beta-casein gene
      expression was being extinguished. Expression of sulfated glycoprotein-2 (SGP-2),
      interleukin-1 beta converting enzyme (ICE) and tissue inhibitor of
      metalloproteinases-1 was upregulated at day 2, when apoptotic cells were seen
      initially. Expression of the matrix metalloproteinases gelatinase A and
      stromelysin-1 and the serine proteinase urokinase-type plasminogen activator,
      which was low during lactation, was strongly upregulated in parallel starting at
      day 4 after weaning, coinciding with start of the collapse of the lobulo-alveolar
      structures and the intensive tissue remodeling in involution. The major sites of
      mRNA synthesis for these proteinases were fibroblast-like cells in the periductal
      stroma and stromal cells surrounding the collapsed alveoli, suggesting that the
      degradative phase of involution is due to a specialized mesenchymal-epithelial
      interaction. To elucidate the functional role of these proteinases during
      involution, at the onset of weaning we treated mice systemically with the
      glucocorticoid hydrocortisone, which is known to inhibit mammary gland
      involution. Although the initial wave of apoptotic cells appeared in the lumina
      of the gland, the dramatic regression and tissue remodeling usually evident by
      day 5 was substantially inhibited by systemic treatment with hydrocortisone. mRNA
      and protein for gelatinase A, stromelysin-1 and uPA were weakly induced, if at
      all, in hydrocortisone-treated mice. Furthermore, mRNA for membrane-type matrix
      metalloproteinase decreased after hydrocortisone treatment and paralleled the
      almost complete inhibition of activation of latent gelatinase A. Concomitantly,
      the gland filled with an overabundance of milk. Our data support the hypothesis
      that there are at least two distinct phases of involution: an initial phase,
      characterized by induction of the apoptosis-associated genes SGP-2 and ICE and
      apoptosis of fully differentiated mammary epithelial cells without visible
      degradation of the extracellular matrix, and a second phase, characterized by
      extracellular matrix remodeling and altered mesenchymal-epithelial interactions,
      followed by apoptosis of cells that are losing differentiated functions.

PMID- 8565831
TI  - The eve stripe 2 enhancer employs multiple modes of transcriptional synergy.
AB  - Previous studies have provided a detailed model for the regulation of even
      skipped (eve) stripe 2 expression in the Drosophila embryo. The bicoid (bcd)
      regulatory gradient triggers the expression of hunchback (hb); these work
      synergistically to activate the stripe in the anterior half of the embryo, bcd
      also coordinates the expression of two repressors, giant (gt) and Kruppel (Kr),
      which define the anterior and posterior borders of the stripe, respectively.
      Here, we report the findings of extensive cis- and trans- complementation
      analyses using a series of defective stripe 2 enhancers in transgenic embryos.
      This study reaches two primary conclusions. First, the strip 2 enhancer is
      inherently 'sensitized' for repression by gt. We propose that gt specifies the
      sharp anterior stripe border by blocking two tiers of transcriptional synergy,
      cooperative binding to DNA and cooperative contact of bound activators with the
      transcription complex. Second, we find that the synergistic activity of hb and
      bcd is 'promiscuous'. For example, a maternally expressed Gal4-Sp1 fusion protein
      can functionally replace hb in the stripe 2 enhancer. This finding challenges
      previous proposals for dedicated hb and bcd interactions in the segmentation
      process.

PMID- 8565833
TI  - Argos transcription is induced by the Drosophila EGF receptor pathway to form an
      inhibitory feedback loop.
AB  - Argos is a secreted molecule with an atypical EGF motif. It was recently shown to
      function as an inhibitor of the signaling triggered by the Drosophila EGF
      receptor (DER). In this work, we determine the contribution of Argos to the
      establishment of cell fates in the embryonic ventral ectoderm. Graded activation
      of DER is essential for patterning the ventral ectoderm. argos mutant embryos
      show expansion of ventral cell fates suggesting hyperactivation of the DER
      pathway. In the embryonic ventral ectoderm, argos is expressed in the ventralmost
      row of cells. We show that argos expression in the ventral ectoderm is induced by
      the DER pathway: argos is not expressed in DER mutant embryos, while it is
      ectopically expressed in the entire ventral ectoderm following ubiquitous
      activation of the DER pathway. argos expression appears to be triggered directly
      by the DER pathway, since induction can also be observed in cell culture,
      following activation of DER by its ligand, Spitz. Argos therefore functions in a
      sequential manner, to restrict the duration and level of DER signaling. This type
      of inhibitory feedback loop may represent a general paradigm for signaling
      pathways inducing diverse cell fates within a population of non-committed cells.

PMID- 8565832
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates adenylate
      cyclase and promotes proliferation of mouse primordial germ cells.
AB  - During migration and for about 2 days after their arrival in the gonadal ridges,
      primordial germ cells (the embryonic precursors of gametes of the adult animal)
      proliferate actively. Certain growth factors, such as stem cell factor and
      leukemia inhibitory factor, seem to be essential for survival, proliferation and
      possibly differentiation of mouse primordial germ cell in vivo and/or in vitro.
      Similarly, increase in intracellular cAMP is followed by a marked enhancement of
      primordial germ cell proliferation, at least in culture. In the present study, we
      show that pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP
      38), two neuropeptides of the secretin-glucagon-vasoactive intestinal polypeptide
      GH-releasing hormone family, stimulate in vitro proliferation of mouse primordial
      germ cells, bind to primordial germ cells and gonadal somatic cells (possibly to
      type I PACAP receptor) and activate adenylate cyclase in the same cells.
      Moreover, PACAP-like immunoreactivity was found in gonadal ridges, mostly on germ
      cell surface. In conclusion, evidence is provided that PGC proliferation can be
      stimulated by certain bioactive polypeptides, thus suggesting a novel regulatory
      role for such compounds in early gonad development.

PMID- 8565834
TI  - Pax1 is expressed during development of the thymus epithelium and is required for
      normal T-cell maturation.
AB  - Pax1 is a transcriptional regulatory protein expressed during mouse embryogenesis
      and has been shown to have an important function in vertebral column development.
      Expression of Pax1 mRNA in the embryonic thymus has been reported previously.
      Here we show that Pax1 protein expression in thymic epithelial cells can be
      detected throughout thymic development and in the adult. Expression starts in the
      early endodermal epithelium lining the foregut region and includes the epithelium
      of the third pharyngeal pouch, a structure giving rise to part of the thymus
      epithelium. In early stages of thymus development a large proportion of thymus
      cells expresses Pax1. With increasing age, the proportion of Pax1-expressing
      cells is reduced and in the adult mouse only a small fraction of cortical thymic
      stromal cells retains strong Pax1 expression. Expression of Pax1 in thymus
      epithelium is necessary for establishing the thymus microenvironment required for
      normal T cell maturation. Mutations in the Pax-1 gene in undulated mice affect
      not only the total size of the thymus but also the maturation of thymocytes. The
      number of thymocytes is reduced about 2- to 5-fold, affecting mainly the CD4+8+
      immature and CD4+ mature thymocyte subsets. The expression levels of major
      thymocyte surface markers remains unchanged with the exception of Thy-1 which was
      found to be expressed at 3- to 4-fold higher levels.

PMID- 8565835
TI  - The dorsal neural tube organizes the dermamyotome and induces axial myocytes in
      the avian embryo.
AB  - Somites, like all axial structures, display dorsoventral polarity. The dorsal
      portion of the somite forms the dermamyotome, which gives rise to the dermis and
      axial musculature, whereas the ventromedial somite disperses to generate the
      sclerotome, which later comprises the vertebrae and intervertebral discs.
      Although the neural tube and notochord are known to regulate some aspects of this
      dorsoventral pattern, the precise tissues that initially specify the
      dermamyotome, and later the myotome from it, have been controversial. Indeed,
      dorsal and ventral neural tube, notochord, ectoderm and neural crest cells have
      all been proposed to influence dermamyotome formation or to regulate myocyte
      differentiation. In this report we describe a series of experimental
      manipulations in the chick embryo to show that dermamyotome formation is
      regulated by interactions with the dorsal neural tube. First, we demonstrate that
      when a neural tube is rotated 180 degrees around its dorsoventral axis, a
      secondary dermamyotome is induced from what would normally have developed as
      sclerotome. Second, if we ablate the dorsal neural tube, dermamyotomes are absent
      in the majority of embryos. Third, if we graft pieces of dorsal neural tube into
      a ventral position between the notochord and ventral somite, a dermamyotome
      develops from the sclerotome that is proximate to the graft, and myocytes
      differentiate. In addition, we also show that myogenesis can be regulated by the
      dorsal neural tube because when pieces of dorsal neural tube and unsegmented
      paraxial mesoderm are combined in tissue culture, myocytes differentiate, whereas
      mesoderm cultures alone do not produce myocytes autonomously. In all of the
      experimental perturbations in vivo, the dorsal neural tube induced dorsal
      structures from the mesoderm in the presence of notochord and floorplate, which
      have been reported previously to induce sclerotome. Thus, we have demonstrated
      that in the context of the embryonic environment, a dorsalizing signal from the
      dorsal neural tube can compete with the diffusible ventralizing signal from the
      notochord. In contrast to dorsal neural tube, pieces of ventral neural tube,
      dorsal ectoderm or neural crest cells, all of which have been postulated to
      control dermamyotome formation or to induce myogenesis, either fail to do so or
      provoke only minimal inductive responses in any of our assays. However,
      complicating the issue, we find consistent with previous studies that following
      ablation of the entire neural tube, dermamyotome formation still proceeds
      adjacent to the dorsal ectoderm. Together these results suggest that, although
      dorsal ectoderm may be less potent than the dorsal neural tube in inducing
      dermamyotome, it does nonetheless possess some dermamyotomal-inducing activity.
      Based on our data and that of others, we propose a model for somite dorsoventral
      patterning in which competing diffusible signals from the dorsal neural tube and
      from the notochord/floorplate specify dermamyotome and sclerotome, respectively.
      In our model, the positioning of the dermamyotome dorsally is due to the absence
      or reduced levels of the notochord-derived ventralizing signals, as well as to
      the presence of dominant dorsalizing signals. These dorsal signals are possibly
      localized and amplified by binding to the basal lamina of the ectoderm, where
      they can signal the underlying somite, and may also be produced by the ectoderm
      as well.

PMID- 8565837
TI  - A fate map of the vegetal plate of the sea urchin (Lytechinus variegatus)
      mesenchyme blastula.
AB  - Previous lineage tracing experiments have shown that the vegetal blastomers of
      cleavage stage embryos give rise to all the mesoderm and endoderm of the sea
      urchin larva. In these studies, vegetal blastomers were labeled no later than the
      sixth cleavage division (60-64 cell stage). In an earlier study we showed that
      single cells in the vegetal plate of the blastula stage Lytechinus variegatus
      embryo could be labeled in situ with the fluorescent, lipophilic dye, DiI(C18),
      and that cells labeled in the central region of the vegetal plate of the
      mesenchyme blastula primarily gave rise to homogeneous clones consisting of a
      single secondary mesenchyme cell (SMC) type (Ruffins and Ettensohn (1993) Dev.
      Biol. 160, 285-288). Our clonal labeling showed that a detailed fate map could be
      generated using the DiI(C18) labeling technique. Such a fate map could provide
      information about the spatial relationships between the precursors of specific
      mesodermal and endodermal cell types and information concerning the movements of
      these cells during gastrulation and later embryogenesis. We have used this method
      to construct the first detailed fate map of the vegetal plate of the sea urchin
      embryo. Ours is a latitudinal map; mapping from the plate center, where the
      mesodermal precursors reside, through the region which contains the endodermal
      precursors and across the ectodermal boundary. We found that the precursors of
      certain SMC types are segregated in the mesenchyme blastula stage vegetal plate
      and that prospective germ layers reside within specific boundaries. To determine
      whether the vegetal plate is radially symmetrical with respect to mesodermal cell
      fates, single blastomeres of four cell stage embryos were injected with lysyl
      rhodamine dextran (LRD). The resulting ectodermal labeling patterns were
      classified and correlated with the SMC types labeled. This analysis indicates
      that the dorsal and ventral blastomers do not contribute equally to SMC
      derivatives in L. variegatus.

PMID- 8565836
TI  - A targeted mouse Otx2 mutation leads to severe defects in gastrulation and
      formation of axial mesoderm and to deletion of rostral brain.
AB  - Mouse Otx2 is a bicoid-class homeobox gene, related to the Drosophila
      orthodenticle (otd) gene. Expression of this gene is initially widespread in the
      epiblast at embryonic day 5.5 but becomes progressively restricted to the
      anterior end of the embryo at the headfold stage. In flies, loss of function
      mutations in otd result in deletion of pre-antennal and antennal segments; which
      leads to the absence of head structures derived from these segments. To study the
      function of Otx2 in mice, we have generated a homeobox deletion mutation in this
      gene. Mice homozygous for this mutation show severe defects in gastrulation and
      in formation of axial mesoderm and loss of anterior neural tissues. These results
      demonstrate that Otx2 is required for proper development of the epiblast and
      patterning of the anterior brain in mice, and supports the idea of evolutionary
      conservation of the function of Otd/Otx genes in head development in flies and
      mice.

PMID- 8565838
TI  - Mouse embryos with paternal duplication of an imprinted chromosome 7 region die
      at midgestation and lack placental spongiotrophoblast.
AB  - Imprinted genomic regions have been defined by the production of mice with
      uniparental inheritance or duplication of homologous chromosome regions. With
      most of the genome investigated, paternal duplication of only distal chromosomes
      7 and 12 results in the lack of offspring, and prenatal lethality is presumed.
      Aberrant expression of imprinted genes in these two autosomal regions is
      therefore strongly implicated in the periimplantation lethality of androgenetic
      embryos. We report that mouse embryos with paternal duplication of distal
      chromosome 7 (PatDup.d7) die at midgestation and lack placental
      spongiotrophoblast. Thus, the much earlier death of androgenones must involve
      paternal duplication of other autosomal regions, acting independently of or
      synergistically with PatDup.d7. The phenotype observed is similar, if not
      identical to, that resulting from mutation of the imprinted distal chromosome 7
      gene, Mash2, which in normal midgestation embryos exhibits spongiotrophoblast
      specific maternally active/paternally inactive (m+/p-) allelic expression. Thus,
      the simplest explanation for the PatDup.d7 phenotype is p-/p- expression of this
      gene. We also confirm that PatDup.d7 embryos lack H19 RNA and posses excess Igf2
      RNA as might be expected from the parental-specific activities of these genes in
      normal embryos.

PMID- 8565839
TI  - Developmental regulation of zebrafish MyoD in wild-type, no tail and spadetail
      embryos.
AB  - We describe the isolation of the zebrafish MyoD gene and its expression in wild
      type embryos and in two mutants with altered somite development, no tail (ntl)
      and spadetail (spt). In the wild-type embryo, MyoD expression first occurs in an
      early phase, extending from mid-gastrula to just prior to somite formation, in
      which cells directly adjacent to the axial mesoderm express the gene. In
      subsequent phases, during the anterior-to-posterior wave of somite formation and
      maturation, expression occurs within particular regions of each somite. In spt
      embryos, which lack normal paraxial mesoderm due to incorrect cell migration,
      early MyoD expression is not observed and transcripts are instead first detected
      in small groups of trunk cells that will develop into aberrant myotomal-like
      structures. In ntl embryos, which lack notochords and tails, the early phase of
      MyoD expression is also absent. However, the later phase of expression within the
      developing somites appears to occur at the normal time in the ntl mutants,
      indicating that the presomitogenesis and somitogenesis phases of MyoD expression
      can be uncoupled. In addition, we demonstrate that the entire paraxial mesoderm
      of wild-type embryos has the potential to express MyoD when Sonic hedgehog is
      expressed ubiquitously in the embryo, and that this potential is lost in some of
      the cells of the paraxial mesoderm lineage in no tail and spadetail embryos. We
      also show that MyoD expression precedes myogenin expression and follows or is
      coincident with expression of snaill in some regions that express this gene.

PMID- 8565840
TI  - Encore, a gene required for the regulation of germ line mitosis and oocyte
      differentiation during Drosophila oogenesis.
AB  - During Drosophila oogenesis, a stem cell daughter undergoes precisely four rounds
      of mitosis to generate a cyst of 16 cells interconnected by cytoplasmic bridges.
      One of the cells becomes the oocyte while the remaining 15 cells differentiate as
      nurse cells. We hve identified a gene, encore, that is involved both in
      regulating the number of germline mitoses and in the process of oocyte
      differentation. Mutations in encore result in exactly one extra round of mitosis
      in the germline. Genetic and molecular studies indicate that this mitotic defect
      may be mediated through the gene bag-of-marbles. The isolation and
      characterization of multiple alleles of encore revealed that they were all
      temperature sensitive for this phenotype. Mutations in encore also affect the
      process of oocyte differentiation. Egg chambers are produced in which the oocyte
      nucleus has undergone endoreplication often resulting in the formation of 16
      nurse cells. We argue that these two phenotypes produced by mutations in encore
      represent two independent requirements for encore during oogenesis.

PMID- 8565841
TI  - Loss of fibroblast growth factor receptors is necessary for terminal
      differentiation of embryonic limb muscle.
AB  - Early in embryogenesis, precursors of the limb musculature are generated in the
      somite, migrate to the limb buds and undergo terminal differentiation. Although
      myogenic differentiation in culture is affected by several growth factors
      including fibroblast growth factor (FGF), it remains uncertain whether migration
      and differentiation of myogenic cells in vivo are directly regulated by such
      growth factors. To investigate the roles of FGF signaling in the regulation of
      myogenesis both in the somite and the limb bud, mosaic chicken embryos were
      generated that consist of somitic cells carrying transgenes expressing one of the
      following: FGF1, FGF4, the FGF receptor type-1 (FGFR1) or its dominant negative
      mutant (delta FGFR1). Cells infected with virus producing FGF ligand migrated
      into the somatopleure without differentiating into myotomal muscle, but
      differentiated into muscle fibers when they arrived in the limb bud. In contrast,
      cells overexpressing FGFR1 migrated into the limb muscle mass but remained as
      undifferentiated myoblasts. Cells infected with the delta FGFR1-producing virus
      failed to migrate to the somatopleure but were capable of differentiating into
      myotomal muscle within the somites. These results suggest that the FGFR-mediated
      FGF signaling (1) blocks terminal differentiation of myogenic cells within the
      somite and (2) sustains myoblast migration to limb buds from the somite, and that
      (3) down-regulation of FGFRs or FGFR signaling is involved in mechanisms
      triggering terminal differentiation of the limb muscle mass during avian
      embryogenesis.

PMID- 8565842
TI  - In vivo effects of neurotrophin-3 during sensory neurogenesis.
AB  - The neurotrophins nerve growth factor, brain-derived neurotrophic factor and
      neurotrophin-3 are structurally related proteins regulating the number of neurons
      in peripheral ganglia of the nervous system. Increased levels of nerve growth
      factor or of brain-derived neurotrophic factor selectively prevent normally
      occurring neuronal death, while the targeted elimination of all three genes
      decreases neuronal numbers. As previous studies indicated that the lack of
      neurotrophin-3 affects sensory ganglia already during gangliogenesis, the levels
      of this neurotrophin were increased during selected periods of chick development.
      We found that early, but not late, applications of neurotrophin-3 lead to a
      marked decrease in neuronal numbers in peripheral sensory ganglia. This decrease
      is not seen with BDNF and does not selectively affect subtypes of dorsal root
      ganglion neurons. It is accompanied by, and might result from, a decrease in the
      number of proliferating neuroblasts in sensory ganglia of treated embryos.

PMID- 8565843
TI  - Distinct subpopulations of enteric neuronal progenitors defined by time of
      development, sympathoadrenal lineage markers and Mash-1-dependence.
AB  - Enteric and sympathetic neurons have previously been proposed to be lineally
      related. We present independent lines of evidence that suggest that enteric
      neurons arise from at least two lineages, only one of which expresses markers in
      common with sympathoadrenal cells. In the rat, sympathoadrenal markers are
      expressed, in the same order as in sympathetic neurons, by a subset of enteric
      neuronal precursors, which also transiently express tyrosine hydroxylase. If this
      precursor pool is eliminated in vitro by complement-mediated lysis, enteric
      neurons continue to develop; however, none of these are serotonergic. In the
      mouse, the Mash-1-/- mutation, which eliminates sympathetic neurons, also
      prevents the development of enteric serotonergic neurons. Other enteric neuronal
      populations, however, including those that contain calcitonin gene related
      peptide are present. Enteric tyrosine hydroxylase-containing cells co-express
      Mash-1 and are eliminated by the Mash-1-/- mutation, consistent with the idea
      that in the mouse, as in the rat, these precursors generate serotonergic neurons.
      Serotonergic neurons are generated early in development, while calcitonin gene
      related peptide-containing enteric neurons are generated much later. These data
      suggest that enteric neurons are derived from at least two progenitor lineages.
      One transiently expresses sympathoadrenal markers, is Mash-1-dependent, and
      generates early-born enteric neurons, some of which are serotonergic. The other
      is Mash-1-independent, does not express sympathoadrenal markers, and generates
      late-born enteric neurons, some of which contain calcitonin gene related peptide.

PMID- 8565844
TI  - ERECT WING, the Drosophila member of a family of DNA binding proteins is required
      in imaginal myoblasts for flight muscle development.
AB  - The erect wing locus of the fruit fly Drosophila melanogaster encodes a protein,
      EWG, that shares extensive homology with the P3A2 DNA binding protein of sea
      urchin and a recently identified mammalian transcription factor. Loss-of-function
      erect wing alleles result in embryonic lethality. Viable alleles of erect wing
      cause severe abnormalities of the indirect flight muscles. We have analyzed the
      spatial pattern of erect wing expression in the developing indirect flight
      muscles during postembryonic development. EWG is detected, 10 hours after
      puparium formation, in myoblasts that will form the indirect flight muscles. The
      early events of muscle development are normal in ewg mutants. However, a few
      hours after the onset of erect wing expression in myoblasts, defects are seen in
      the developing indirect flight muscles which subsequently degenerate. We present
      results that show that the normal development of the indirect flight muscles
      requires erect wing expression in the progenitor myoblasts themselves. Finally,
      we examine the role of target muscles in the arborization of motor axons by
      studying the developing innervation to the flight muscle in erect wing mutants.
      Our study demonstrates, for the first time, a role for a regulatory gene
      expressed in imaginal myoblasts in Drosophila.

PMID- 8565845
TI  - The establishment of the hepatic architecture is a prerequisite for the
      development of a lobular pattern of gene expression.
AB  - We have studied the expression patterns of ammonia-metabolising enzymes and serum
      proteins in intrasplenically transplanted embryonic rat hepatocytes by in situ
      hybridisation and immunohistochemical analysis. The enzymic phenotype of
      individually settled hepatocytes was compared with that of hepatocytes being
      organised into a three-dimensional hepatic structure. Our results demonstrate
      that development towards the terminally differentiated state with zonal
      differences in enzyme content requires the incorporation of hepatocytes into
      lobular structures. Outside such an architectural context, phenotypic maturation
      becomes arrested and hepatocytes linger in the protodifferentiated state. These
      features identify the foetal period as a crucial time for normal liver
      development and show that the establishment of the terminally differentiated
      hepatocellular phenotype, beginning with the differentiation of hepatocytes from
      the embryonic foregut, is realised via a multistep process.

PMID- 8565846
TI  - Spatial and temporal information processing in the sea urchin embryo: modular and
      intramodular organization of the CyIIIa gene cis-regulatory system.
AB  - The CyIIIa cytoskeletal actin gene of Strongylocentrotus purpuratus is expressed
      specifically in the aboral ectoderm. In earlier work we identified a 2.3 kb cis
      regulatory region that is necessary and sufficient for correct spatial and
      temporal expression of a CyIIIa.CAT gene. This region includes about 20 sites of
      specific protein-DNA interaction, at which at least nine different transcription
      factors may be bound. All except two of these factors have been cloned. In this
      work we have analyzed by deletion or mutagenesis each specific interaction. A
      specific function was identified for every binding site examined. These
      individual functions include control of amplitude and timing of expression at
      different phases of embryogenesis, and control of spatial expression. We show
      that particular negative regulatory interactions are required to repress
      expression of the CyIIIa.CAT construct in oral ectoderm and in skeletogenic
      mesenchyme at different stages. In further experiments we determined the overall
      functional organization of the CyIIIa cis-regulatory system, and we show that
      this system is modular in its regulatory structure. The 'proximal module' (with
      respect to the transcription start site) extends upstream for about 800 base
      pairs, and includes nine target sites serviced by six different transcription
      factors. Its major role is to establish CyIIIa expression in the aboral ectoderm
      territory as the blastomere founder cells are specified and the oral-aboral axis
      is determined, and to activate the CyIIIa gene late in cleavage. The 'middle
      module,' which lies upstream of the proximal module, acquires major control of
      CyIIIa function after the blastula stage. It includes six target sites, serviced
      by four different factors. The middle module is responsible for a sharp increase
      in expression occurring during gastrulation, mediated by the positively acting
      factors that bind within it. The middle module also includes sites at which two
      different negatively acting spatial control factors bind, the functions of which
      are required for correct spatial expression late in embryogenesis. The 'distal
      module' contains a number of sites at which a positively acting factor binds, but
      this module exercises no spatial regulatory function. Interactions within the
      distal module are required for the normal levels of function of both the proximal
      and middle modules.

PMID- 8565847
TI  - Common origin and developmental dependence on c-ret of subsets of enteric and
      sympathetic neuroblasts.
AB  - c-ret encodes a tyrosine kinase receptor that is necessary for normal development
      of the mammalian enteric nervous system. Germline mutations in c-ret lead to
      congenital megacolon in humans, while a loss-of-function allele (ret.k-) causes
      intestinal aganglionosis in mice. Here we examine in detail the function of c-ret
      during neurogenesis, as well as the lineage relationships among cell populations
      in the enteric nervous system and the sympathetic nervous system that are
      dependent on c-ret function. We report that, while the intestine of newborn ret.k
      mice is devoid of enteric ganglia, the esophagus and stomach are only partially
      affected; furthermore, the superior cervical ganglion is absent, while more
      posterior sympathetic ganglia and the adrenal medulla are unaffected. Analysis of
      mutant embryos shows that the superior cervical ganglion anlage is present at
      E10.5, but absent by E12.5, suggesting that c-ret is required for the survival or
      proliferation of sympathetic neuroblasts. In situ hybridization studies, as well
      as direct labelling of cells with DiI, indicate that a common pool of neural
      crest cells derived from the postotic hindbrain normally gives rise to most of
      the enteric nervous system and the superior cervical ganglion, and is uniquely
      dependent on c-ret function for normal development. We term this the
      sympathoenteric lineage. In contrast, a distinct sympathoadrenal lineage derived
      from trunk neural crest forms the more posterior sympathetic ganglia, and also
      contributes to the foregut enteric nervous system. Overall, our studies reveal
      previously unknown complexities of cell lineage and genetic control mechanisms in
      the developing mammalian peripheral nervous system.

PMID- 8565848
TI  - Activation and function of Notch at the dorsal-ventral boundary of the wing
      imaginal disc.
AB  - The cells along the dorsoventral boundary of the Drosophila wing imaginal disc
      have distinctive properties and their specification requires Notch activity.
      Later in development, these cells will form the wing margin, where sensory organs
      and specialised trichomes appear in a characteristic pattern. We find that Notch
      is locally activated in these cells, as demonstrated by the restricted expression
      of the Enhancer of split proteins in dorsal and ventral cells abutting the D/V
      boundary throughout the third larval instar. Furthermore other genes identified
      by their involvement in Notch signaling during neurogenesis, such as Delta and
      Suppressor of Hairless, also participate in Notch function at the dorsoventral
      boundary. In addition, Serrate, a similar transmembrane protein to Delta, behaves
      as a ligand required in dorsal cells to activate Notch at the boundary. Notch
      gain-of-function alleles in which Notch activity is not restricted to the
      dorsoventral boundary cause miss-expression of cut and wingless and overgrowth of
      the disc, illustrating the importance of localised Notch activation for wing
      development.

PMID- 8565849
TI  - The alignment of the axis of asymmetry in regenerating protoplasts of the moss,
      Ceratodon purpureus, is determined independently of axis polarity.
AB  - Ceratodon protoplasts regenerate by polar outgrowth to form cell filaments. The
      kinetics of regeneration show that some cellular event has to be completed before
      regeneration can be initiated. The development of the regeneration axis is
      strongly influenced by light, with axis alignment and axis polarity being fixed
      independently. We define axis alignment as the relationship of the regeneration
      axis to the incident light, independent of polarity. Thus protoplasts
      regenerating directly towards, or directly away from the light source are defined
      as being similarly aligned but with opposite polarity. Protoplasts that
      regenerate in unidirectional red light form axes that are aligned parallel to the
      light direction, with about 70% being polarised towards the light and about 30%
      away. In unidirectional blue or white light, almost all protoplasts regenerate
      towards the light but axis alignment is determined less stringently. Re
      orientation of protoplasts regenerating in unidirectional light shows that axis
      alignment is fixed between 8 and 9 hours before protoplasts regenerate and that
      axis polarity is fixed later. When protoplasts are removed from directional light
      to either non-directional light or to darkness, regeneration axes continue to be
      aligned by the earlier directional stimulus for at least 24 hours. Thus although
      axis alignment is fixed only about 8 hours before regeneration, in the absence of
      contradictory information about directionality in the light environment,
      protoplasts retain a memory of light direction for much longer. However, both
      reorientation and removal from a directional light field have profound effects on
      axis polarity; the pattern observed in undisturbed protoplasts being lost. To
      account for these observations, we propose that separate gradients are
      established independently to determine the alignment and polarity of the
      regeneration axis respectively. The alignment gradient is established rapidly and
      is steeper in red than in blue or white light, the polarity gradient is
      established slowly and is steeper in white or blue light than in red. These
      studies will now allow a genetic dissection of these processes in moss.

PMID- 8565850
TI  - Contact inhibition/collapse and pathfinding of neural crest cells in the
      zebrafish trunk.
AB  - Neural crest cells in the trunk of vertebrate embryos have a choice of pathways
      after emigrating from the neural tube: they can migrate in either the medial
      pathway between somites and neural tube, or the lateral pathway between somites
      and epidermis. In zebrafish embryos, the first cells to migrate all choose the
      medial pathway. High resolution imaging of cells in living embryos suggests that
      neural crest cells do so because of repulsion by somites: cells take the medial
      pathway because the lateral somite surface triggers a paralysis and retraction of
      protrusions (contact inhibition or collapse) when the medial surface does not.
      Partial deletion of somites, using the spadetail mutation allows precocious entry
      into the lateral pathway, but only where somites are absent, supporting the
      notion that an inhibitory cue on somites delays entry. Growth cones of Rohon
      Beard cells enter the lateral pathway before neural crest cells, demonstrating
      that there is no absolute barrier to migration. These data, in addition to
      providing a detailed picture of neural crest cells migrating in vivo, suggest
      that neural crest cells, like neuronal growth cones, are guided by a specific cue
      that triggers 'collapse' of active protrusions.

PMID- 8565851
TI  - A sperm-supplied factor required for embryogenesis in C. elegans.
AB  - The paternal-effect embryonic-lethal gene, spe-11, is required for normal
      development of early C. elegans embryos. Spe-11 embryos fail to complete meiosis,
      form a weak eggshell, fail to orient properly the first mitotic spindle, and fail
      to undergo cytokinesis. Here we report cloning and sequencing of the spe-11 gene,
      which encodes a novel protein. As predicted by the paternal-effect mutant
      phenotype, the gene is expressed during spermatogenesis but is not detectable in
      females undergoing oogenesis, and the protein is present in mature sperm. To
      investigate whether SPE-11's essential function is during spermatogenesis or
      whether sperm-delivered SPE-11 functions in the newly fertilized embryo, we
      engineered animals to supply SPE-11 to the embryo through the oocyte rather than
      through the sperm. We found that maternal expression is sufficient for embryonic
      viability. This result demonstrates that SPE-11 is not required during
      spermatogenesis, and suggests that SPE-11 is a sperm-supplied factor that
      participates directly in development of the early embryo. In contrast to the many
      known maternal factors required for embryogenesis, SPE-11 is the first paternally
      contributed factor to be genetically identified and molecularly characterized.

PMID- 8565852
TI  - Rpx: a novel anterior-restricted homeobox gene progressively activated in the
      prechordal plate, anterior neural plate and Rathke's pouch of the mouse embryo.
AB  - We have isolated a new murine homeobox gene, Rpx (for Rathke's pouch homeobox),
      that is dynamically expressed in the prospective cephalic region of the embryo
      during gastrulation. Early expression is seen in the anterior midline endoderm
      and prechordal plate precursor. Expression is subsequently activated in the
      overlying ectoderm of the cephalic neural plate, suggesting that inductive
      contact with Rpx-expressing mesendoderm is required for this expression.
      Subsequently, Rpx expression is extinguished in the mesendoderm while remaining
      in the prospective prosencephalic region of the neural plate ectoderm.
      Ultimately, transcripts become restricted to Rathke's pouch, the primordium of
      the pituitary, which is known to be derived from the most anterior ectoderm of
      the early embryo. Down regulation of Rpx in the pouch coincides with the
      differentiation of pituitary-specific cell types. Rpx is the earliest known
      marker for the pituitary primordium, suggestive of a role in the early
      determination or differentiation of the pituitary. Since Rpx is expressed so
      dynamically and so early in the anterior region of the embryo, and since its
      early expression domain is much more extensive than the region fated to form the
      pituitary, it is likely that Rpx is involved in the initial determination of the
      anterior (prechordal) region of the embryo.

PMID- 8565854
TI  - Clones in the chick diencephalon contain multiple cell types and siblings are
      widely dispersed.
AB  - The thalamus, hypothalamus and epithalamus of the vertebrate central nervous
      system are derived from the embryonic diencephalon. These regions of the nervous
      system function as major relays between the telencephalon and more caudal regions
      of the brain. Early in development, the diencephalon morphologically comprises
      distinct units known as neuromeres or prosomeres. As development proceeds,
      multiple nuclei, the functional and anatomical units of the diencephalon, derive
      from the neuromeres. It was of interest to determine whether progenitors in the
      diencephalon give rise to daughters that cross nuclear or neuromeric boundaries.
      To this end, a highly complex retroviral library was used to infect diencephalic
      progenitors. Retrovirally marked clones were found to contain neurons, glia and
      occasionally radial glia. The majority of clones dispersed in all directions,
      resulting in sibling cells populating multiple nuclei within the diencephalon. In
      addition, several distinctive patterns of dispersion were observed. These
      included clones with siblings distributed bilaterally across the third ventricle,
      clones that originated in the lateral ventricle, clones that crossed neuromeric
      boundaries, and clones that crossed major boundaries of the developing nervous
      system, such as the diencephalon and mesencephalon. These findings demonstrate
      that progenitor cells in the diencephalon are multipotent and that their
      daughters can become widely dispersed.

PMID- 8565853
TI  - A distinct cyclin A is expressed in germ cells in the mouse.
AB  - In this paper, the existence of two A-type cyclins in the mouse is demonstrated.
      In the adult mouse, the expression of cyclin A1, which has greatest sequence
      identity with Xenopus cyclin A1, is restricted to germ cells. In contrast cyclin
      A2, which has greatest sequence identity with human cyclin A and Xenopus cyclin
      A2, is expressed in all tissues analysed. In order to explore the function of
      cyclin A1 in germ cells, its expression during the meiotic cell cycle and its
      associated kinase subunits have been characterised in the testis. The levels of
      cyclin A1 mRNA rise dramatically in late pachytene spermatocytes and become
      undetectable soon after completion of the meiotic divisions; thus its expression
      is cell cycle regulated. In lysates of germ cells from adult testes, cyclin A1 is
      present in p13suc1 precipitates, and cyclin A1 immunoprecipitates possess histone
      H1 kinase activity. Three kinase partners of cyclin A1 were identified: p34cdc2,
      a polypeptide of 39 x 10(3) M(r) that is related to p33cdk2 and, in lesser
      quantities, p33cdk2. Cyclin A1 was also detected in oocytes; in metaphase I and
      metaphase II oocytes, a proportion of the cyclin A1 colocalises with the spindle,
      possibly suggestive of a functional interaction. These data indicate that
      mammalian germ cells contain cyclin A1-dependent kinases that either act as a
      substitute for, or in addition to, the cyclin A2-dependent kinases characterised
      in somatic tissues.

PMID- 8565856
TI  - The WUSCHEL gene is required for shoot and floral meristem integrity in
      Arabidopsis.
AB  - Self perpetuation of the shoot meristem is essential for the repetitive
      initiation of shoot structures during plant development. In Arabidopsis shoot
      meristem maintenance is disrupted by recessive mutations in the WUSCHEL (WUS)
      gene. The defect is evident at all developmental stages and is restricted to
      shoot and floral meristems, whereas the root meristem is not affected. wus
      mutants fail to properly organize a shoot meristem in the embryo.
      Postembryonically, defective shoot meristems are initiated repetitively but
      terminate prematurely in aberrant flat structures. In contrast to wild-type shoot
      meristems, primordia initiation occurs ectopically across mutant apices,
      including the center, and often new shoot meristems instead of organs are
      initiated. The cells of wus shoot apices are larger and more vacuolated than wild
      type shoot meristem cells. wus floral meristems terminate prematurely in a
      central stamen. Double mutant studies indicate that the number of organ primordia
      in the center of wus flowers is limited, irrespective of organ identity and we
      propose that meristem cells are allocated into floral whorl domains in a
      sequential manner. WUS activity also appears to be required for the formation of
      supernumerary organs in the center of agamous, superman or clavata1 flowers,
      suggesting that the WUS gene acts upstream of the corresponding genes. Our
      results suggest that the WUS gene is specifically required for central meristem
      identity of shoot and floral meristems to maintain their structural and
      functional integrity.

PMID- 8565855
TI  - Severe defects in the formation of epaxial musculature in open brain (opb) mutant
      mouse embryos.
AB  - The differentiation of somite derivatives is dependent on signals from
      neighboring axial structures. While ventral signals have been described
      extensively, little is known about dorsal influences, especially those from the
      dorsal half of the neural tube. Here, we describe severe phenotypic alterations
      in dorsal somite derivatives of homozygous open brain (opb) mutant mouse embryos
      which suggest crucial interactions between dorsal neural tube and dorsal somite
      regions. At Theiler stage 17 (day 10.5 post coitum) of development, strongly
      altered expression patterns of Pax3 and Myf5 were observed in dorsal somite
      regions indicating that the dorsal myotome and dermomyotome were not
      differentiating properly. These abnormalities were later followed by the absence
      of epaxial (dorsal) musculature; whereas, body wall and limb musculature formed
      normally. Analysis of Mox1 and Pax1 expression in opb embryos revealed additional
      defects in the differentiation of the dorsal sclerotome. The observed
      abnormalities coincided with defects in differentiation of dorsal neural tube
      regions. The implications of our findings for interactions between dorsal neural
      tube, surface ectoderm and dorsomedial somite regions in specifying epaxial
      musculature are discussed.

PMID- 8565858
TI  - Slag burn tympanic membrane perforation.

PMID- 8565859
TI  - Consequences of recurrent vocal fold hemorrhage.

PMID- 8565857
TI  - The C. elegans vulval induction gene lin-2 encodes a member of the MAGUK family
      of cell junction proteins.
AB  - The lin-2 gene is required for the induction of the Caenorhabditis elegans vulva.
      Vulval development is initiated by a signal from the anchor cell that is
      transduced by a receptor tyrosine kinase/Ras pathway. We show that lin-2 acts in
      the vulval precursor cell P6.p, downstream of lin-3 EGF and upstream of let-60
      ras, to allow expression of the 1 degrees cell fate. lin-2 encodes a protein of
      relative molecular mass 109,000 (LIN-2A) with regions of similarity to CaM kinase
      II and membrane-associated guanylate kinases. Mutant lin-2 transgenes designed to
      lack either protein kinase or guanylate kinase activity are functional,
      indicating that LIN-2A has a structural rather than an enzymatic role in vulval
      induction. Most or all identified membrane-associated guanylate kinases are
      components of cell junctions, including vertebrate tight junctions and arthropod
      septate junctions in epithelia. Thus, LIN-2A may be a component of the cell
      junctions of the epithelial vulval precursor cells that is required for signaling
      by the receptor tyrosine kinase LET-23. We propose that LIN-2A is required for
      the localization of one or more signal transduction proteins (such as LET-23) to
      either the basal membrane domain or the cell junctions, and that mislocalization
      of signal transduction proteins in lin-2 mutants interferes with vulval
      induction.

PMID- 8565860
TI  - Severe columellar deficiency--grafts to the rescue.

PMID- 8565861
TI  - Environmental controls: dust mite. Part II: Acaricides.

PMID- 8565862
TI  - Endoscopic excision of a large benign antral lesion via a modified ("mini")
      Caldwell-Luc procedure.

PMID- 8565863
TI  - Voice abnormalities in short stature syndromes.
AB  - Patients with short stature have a high incidence of voice and laryngeal
      abnormalities. In sixteen patients with short stature of various etiologies,
      these abnormalities appeared to be unrelated to hearing loss or other
      otolaryngologic problems. However, in many patients they were associated with
      typical symptoms and signs of voice abuse. Physicians and speech-language
      pathologists caring for patients with short stature should be alert for voice
      problems, and should consider instituting early voice education, diagnosis and
      treatment.

PMID- 8565864
TI  - Airway obstruction in children with infectious mononucleosis.
AB  - Epstein-Barr Virus (EBV) infection generally has a benign clinical course. Upper
      airway obstruction is a known complication requiring the otolaryngologist's
      attention. EBV is usually associated with adolescence but has been increasingly
      documented in younger children. We review 36 pediatric admissions for infectious
      mononucleosis over a 12-year period at our institution, 11 of which required
      consultation for airway obstruction. Airway management was based on clinical
      severity and ranged from monitored observation, with or without nasopharyngeal
      stenting, to prolonged intubation or emergent tonsilloadenoidectomy. A rare case
      of a four-year-old with near total upper airway obstruction secondary to
      panpharyngeal and transglottic inflammatory edema prompted this review and is
      reported. The otolaryngologist must recognize the potential severity of EBV
      related airway compromise and be prepared to manage it.

PMID- 8565865
TI  - A pathway for information transmission to the ear.
AB  - The use of implantable hearing aids and cochlear implants as an aid to
      neurosensory deafness is becoming an established procedure. The transmission of a
      processed speech signal is accomplished either transcutaneously via
      radiofrequency or percutaneously by connector coupling. Whereas the former is
      sensitive to electromagnetic interference, the latter increases the risk of
      infection. To overcome these disadvantages, an infrared (IR) system for
      transmission through the tympanic membrane was devised and tested. The
      transmitter/receiver consisted of an IR light emitting diode (LED; 920nm) and a
      photovoltaic cell. The LED was placed inside the auditory canal of four dogs and
      the photovoltaic cell in the tympanic cavity over the cochlear promontory. A
      sinusoidal signal modulation was applied to the LED. The emitted signal was
      detected undistorted after crossing the tympanic membrane, with an average
      absorbance of 20%. High-frequency cut-off was adequate for cochlear implant
      purposes and audio prosthetic devices in general. The authors conclude that the
      tympanic membrane may be used as a translucent sealed interface to transmit data
      in the audio range to the middle and inner ears, with small power loss, good
      frequency response, and immunity to interface.

PMID- 8565866
TI  - Overexpression of p53 in laryngeal carcinoma: clinicopathological implications.
AB  - The aims of this study were to determine the incidence of p53 overexpression in
      squamous cell carcinoma of the larynx and to establish whether or not this bore
      any relationship to survival, location, stage, histological differentiation,
      nuclear atypia, mitotic activity, stromal desmoplasia, tumor-associated tissue
      eosinophilia, or stromal lymphoplasmocytic infiltration. Paraffin blocks from 51
      cases of laryngeal squamous cell carcinoma with a minimum follow-up period of 36
      months were recut and stained immunohistologically with anti-p53 antibody using
      the streptavidin-biotin technique. Results were compared with clinicopathological
      features with Kruskal-Wallis and Mann-Whitney tests. Sixty-three percent of
      tumors showed positive staining for p53, and in addition, 15% of the sections
      with adjacent normal or dysplastic mucosa showed positive staining. No
      relationship between p53 staining and prognosis or any other one of the
      aforementioned clinicopathological parameters was observed. Although p53
      overexpression is a common feature in laryngeal carcinomas, it does not seem to
      have an impact on prognosis and it does not bear any relationship to the
      aforementioned clinicopathological parameters.

PMID- 8565867
TI  - Atypical forms of paroxysmal positional nystagmus.
AB  - Benign paroxysmal positional vertigo (BPPV) is a common cause of vertigo, and has
      a typical constellation of physical findings. Atypical forms of paroxysmal
      positional nystagmus (APPN) also exist, and are thought to represent conditions
      which are in fact not "benign". We studied 100 consecutive patients with
      positional vertigo in order to learn whether APPN differed from classic BPPV in
      etiology or clinical fate, and to learn the incidence of central nervous system
      (CNS) disorders in these patients. APPN was present in 38% of these patients with
      diverse causes. One-fourth had CNS disorders or vascular insufficiency, the
      remainder, otogenic or idiopathic. APPN was more likely than BPPV to have a
      prolonged (persistent or recurring) clinical course. Although most cases
      eventually resolved, duration of symptoms tended to be longer, regardless of
      etiology. We conclude that APPN has a less favorable prognosis than typical BPPV,
      and that a CNS etiology should be suspected in prolonged cases.

PMID- 8565868
TI  - Early oral feeding after total laryngectomy.

PMID- 8565869
TI  - Preoperative HIV testing.

PMID- 8565870
TI  - The yeast connection and the woman.

PMID- 8565871
TI  - Experimental study of interactions between five trace elements--Cu, Ag, Se, Zn,
      and Hg--toward their bioaccumulation by fish (Brachydanio rerio) from the direct
      route.
AB  - Actions and interactions between five elements--copper, zinc, silver, selenium,
      and methyl mercury--toward their bioaccumulation in fish (Brachydanio rerio) were
      studied after 12 days exposure, via the direct contamination route. The
      experimental approach was based on a centered composite factorial design; 43
      different contamination conditions were studied simultaneously, with five
      concentration levels in the water for each element. Contaminated media were
      cyclically renewed (48 hr renewal cycle), in order to control the fish exposure
      conditions. Data treatment was essentially based on the multiple regression
      technique, applied successively to the complete factorial design (2(5) = 32
      conditions) and to the centered composite design (43 conditions). Results show a
      complex set of actions and interactions between the elements. The most striking
      result is a marked interaction between silver and methyl mercury: when Ag is
      present in the water jointly with MeHg, it exerts a negative action on Hg
      bioaccumulation in the fish, at the whole organism level. Bioaccumulation of
      silver is also significantly influenced by the presence of Zn, Cu, and Se in the
      water, the action of these three elements producing an increase in the amounts of
      Ag in the organisms. This study corresponds to an exploratory phase in order to
      reveal interaction effects on the bioaccumulation processes by fish and then to
      set up more in-depth analysis to increase progressively the understanding of the
      ecotoxicological mechanisms involved.

PMID- 8565872
TI  - Chromium-induced sexual reproduction gives rise to a Cr-tolerant progeny in
      Scenedesmus acutus.
AB  - A clonal population of Scenedesmus acutus was treated for 3 months with 1
      mg/liter Cr(VI) and then returned to Cr-free medium. After several months, the
      cells were treated with different Cr concentrations and then subjected to a
      series of morphological observations and metabolic tests. The results, compared
      with those obtained with a normal cell population treated in the same way,
      demonstrate that the progeny of algae subjected to the prolonged Cr treatment has
      acquired tolerance to the metal, as it can survive and grow in the presence of Cr
      concentrations that are lethal to normal cells. An ultrastructural description of
      gametes and zygotes is also given.

PMID- 8565873
TI  - Toxic effects, at three pH levels, of two reference molecules on common carp
      embryo.
AB  - Early life-stage survival, motility, and growth toxicity tests were carried out
      on common carp (Cyprinus carpio L.) endotrophic embryo, with two reference
      molecules (captafol and DNOC), from fertilization to the end of the first two
      thirds period of mortalities by starvation. Thirteen days duration exposure was
      performed in daily renewed medium, at 24.5 degrees C, in standard synthetic
      water, at three pHs (6.9, 7.8, 9.0), in the presence of 10 mM/liter nontoxic pH
      buffer. Nominal concentrations of toxicants were 0.0, 0.25, 0.5, 1.0, and 2.0
      mg/liter. Toxic effects on survival, motility, and growth decreased with
      increasing pH. From pH 6.9 to 9.0, the "no-observed-effect concentrations"
      differed by a factor greater than 8. Motility and growth cannot be considered, at
      population level, as true sublethal embryo-larval toxicity criteria. The
      toxicological interpretation of these results is discussed. They confirm the need
      of multifactorial methods for toxic risks and effects assessment on fish early
      life stages in the environment.

PMID- 8565874
TI  - Comparison of the toxicity of various lignin-related phenolic compounds toward
      selected fungi perfecti and fungi imperfecti.
AB  - A selection of 88 micromycetes belonging to various taxonomic groups was grown on
      malt-agar medium containing different lignin-related phenolic compounds (ferulic,
      protocatechuic, syringic and vanillic acids, catechol, guaiacol, and phenol) at
      concentrations ranging from 100 to 1000 mg/liter. Growth and morphological
      changes were recorded after 15 days of incubation. Behavior of fungi in contact
      with the different phenolics were compared. Some strains were very sensitive and
      might constitute specific or general bioindicators of pollution. The
      relationships between origin of isolates or constitutive phenoloxidase activity
      and resistance or sensitivity of fungi to phenolics were researched. No evidence
      of implication of these two parameters was found.

PMID- 8565875
TI  - Determination of heavy metals distribution in the anoxic sediment slurries by
      chemical sequential fractionation.
AB  - An analytical procedure involving chemical sequential fractionation was used for
      quantification of partitioning of some metals (Cu, Cr, and Cd) in anoxic sediment
      slurries (10 or 20% w/v) into six fractions. These fractions include
      exchangeable, bound to carbonate, easily reducible, moderately reducible, bound
      to organic, and residue fractions. Low amounts of Cu (10-11%) and moderate
      amounts of Cr (38%) and Cd (38-39%) were retained as the easily reducible and
      moderately reducible fractions which represented the mobile forms of metals in
      the sediments. The amendment of different amounts (20 or 100 mg/liter) of metals
      into the anoxic sediment slurries (10% w/v) resulted in a different percentage
      distribution of metals into six fractions. The amount of Cd in the carbonate
      fraction increased significantly after Cd amendment. The percentage of Cu or Cr
      in the easily reducible and moderately reducible fractions increased, while those
      in the residual fraction decreased as the amount of Cu or Cr amended into the
      sediment slurries increased.

PMID- 8565876
TI  - Segment specificity of the cytological response in rainbow trout (Oncorhynchus
      mykiss) renal tubules following prolonged exposure to sublethal concentrations of
      atrazine.
AB  - Cytopathological alterations in proximal (PS I, PS II) and distal segments (DS)
      of rainbow trout (Oncorhynchus mykiss) renal tubules following exposure to 0, 10,
      20, 40, 80, and 160 micrograms/liter atrazine for 4 weeks were investigated by
      means of electron microscopy. Cellular responses were clearly dose-dependent with
      a gradual increase in variability and intensity of effects. Ultrastructural
      modifications in PS I and II were observed from 10 micrograms/liter atrazine, in
      DS from 20 micrograms/liter. In PS I, major changes included proliferation of
      smooth endoplasmic reticulum, atypical mitochondria and lysosomes, as well as
      gradual alterations of the apical plasmalemma. Typical changes in PS II cells
      were a proliferation of peroxisomes and ring- and cup-shaped mitochondria, as
      well as alterations in the basal labyrinth; DS cells were characterized by a
      proliferation of atypical mitochondria with longitudinally oriented cristae,
      disorganization of Golgi fields and vacuolization of the cell base. Results
      document that different segments of the renal tubule in rainbow trout react not
      only with different levels of sensitivity to atrazine exposure, but also in a
      segment-specific way. Moreover, comparison of effects induced by atrazine with
      those resulting from chronic exposure to the herbicide linuron revealed a
      distinct substance specificity in the reaction of different tubular segments.

PMID- 8565877
TI  - In vivo metabolism of benzo(a)pyrene in a lower vertebrate, the newt Pleurodeles
      walt.
AB  - The capacity of the newt to metabolize benzo(a)pyrene in vivo was investigated
      qualitatively and quantitatively: metabolism was found to be rapid. Treatment of
      bile with beta-glucuronidase and aryl-sulfatase released high proportions of
      diols and quinones. 3-Methylcholanthrene treatment shortened the elimination half
      life of benzo(a)pyrene which was about three times shorter than the half-life
      found for non-3-methylcholanthrene-pretreated animals. Thus, a greater proportion
      of benzo(a)pyrene was converted into water-soluble products.

PMID- 8565878
TI  - Pesticides and phytoseiid mites: strategies for risk assessment.
AB  - Laboratory toxicity trials may predict effects of chemicals under field
      conditions, but errors are inevitable. A chemical may be presumed harmless when
      in fact it has a detrimental effect, or it may appear highly toxic in the
      laboratory, but not in the field. Error rates depend on experimental setups,
      evaluation criteria, and ecological attributes, such as dietary range, of the
      organisms under study. The authors analyze results of standardized toxicity
      studies of pesticides on four species of predatory mites and assess the
      feasibility of drawing accurate conclusions from laboratory trials alone. This is
      by contrasting laboratory and field data, while varying interpretation criteria.
      At a 5% critical error rate, it was found that correspondence between lab and
      field experiments is only obtained for products harmless to Typhlodromus pyri.
      For this species these constitute only 30% of the total number of products in our
      database. Outcomes from lab tests with Amblyseius andersoni correspond with field
      results (for A. andersoni and A. finlandicus) either for products yielding
      harmless or for products yielding harmful side effects. The decision rules
      required to reach either classification are not compatible and hinge on field
      thresholds that may be unrealistic. For Phytoseiulus persimilis only harmful
      insecticides and harmless fungicides enabled the setting of decision rules that
      resulted in correspondence between lab and field trials of more than 95%. Why
      these species require different interpretation criteria is discussed together
      with suggestions for improvement of existing test protocols and the feasibility
      of using indicator species.

PMID- 8565879
TI  - CO2 production in three earthworm species exposed to terbuthylazine and
      carbofuran in food.
AB  - Studies were conducted in the laboratory to determine the influence of sublethal
      doses of pesticides on the respiration of earthworms. Three different lumbricids
      were exposed to different concentrations of terbuthylazine and carbofuran for up
      to 12 weeks by allowing them to feed on contaminated plant material. After
      different exposure periods the CO2 output of the worms was determined by gas
      chromatography. High terbuthylazine concentrations generally increased CO2
      production, whereas the low concentration tended to decrease it, especially in
      two of the three species studied. Low carbofuran concentration increased the CO2
      expired in all the species; the high dose negatively affected the respiration in
      Lumbricus terrestris and L. rubellus after 3 weeks and in Eisenia andrei after 4
      weeks of exposure.

PMID- 8565880
TI  - Heavy metals in aquatic plants and sediments from water systems in Macedonia,
      Greece.
AB  - Heavy metal concentrations were surveyed in several species of aquatic
      macrophytes and in sediments of a lake and four rivers from Macedonia, northern
      Greece. Acid digestion of sediments and plant material and the subsequent use of
      atomic absorption spectrometry were the analytical methodologies followed for the
      analysis. Values were variable within each species while differences in metal
      contamination among the studied water ecosystem were also found. The lake was
      less contaminated than the rivers, the contamination of which is dependent on the
      metal species. Sediment had greater Cu, Pb, and Ni contamination than the aquatic
      plants, whereas the reverse was the case for Zn, Cd, and Mn. The mean heavy metal
      contents of the sediments and aquatic plants were in the descending order of Mn >
      Zn > Ni > Cu > Pb > Cd, whereas in the accumulation of metals by plant tissues,
      the corresponding order was root > rhizomes > leaf > flower > stem > seed.

PMID- 8565881
TI  - Acute toxicity of the oil dispersant corexit 9554 to marine organisms.
AB  - The acute toxicity of a surfactant-based oil dispersant, Corexit 9554, to the
      early life stages of four marine species was identified using a closed, flow
      through exposure system. Standardized, spiked exposures were used in order to
      impart a measure of reality to the data. The species were taxonomically diverse:
      a mollusc, the red abalone (Haliotis rufescens); a fish, the topsmelt (Atherinops
      affinis); a crustacean, the kelp forest mysid (Holmesimysis costata); and a
      macroalga, the giant kelp (Macrocystis pyrifera). Results indicated the Haliotis
      test to be most sensitive, followed by the Macrocystis test, and the Atherinops
      test, with the Holmesimysis test being least sensitive. Median-effect
      concentration estimates for the four species ranged from 8.0 to 184.3 initial
      ppm, a > 20-fold difference. Differences in sensitivity of the four tests were
      likely the result of both internal (morphological, physiological, etc.) and
      external (life stage, endpoint, etc.) factors.

PMID- 8565882
TI  - Factors regulating methyl mercury uptake in a cyanobacterium.
AB  - The simultaneous addition of dithiothreitol (DTT), mercaptoethanol, and
      glutathione (30 microM each) and CH3Hg+ to Nostoc calcicola cells reduced CH3Hg+
      uptake in the order GSH > DTT > mercaptoethanol. However, the preexposure of
      cyanobacterial cells to similar thiols resulted in different pattern of CH3Hg+
      uptake in the sequence: GSH > mercaptoethanol > DTT. Light-grown cyanobacterial
      cells demonstrated a faster initial uptake of CH3Hg+ (rate 0.619 mumol CH3Hg+ mg
      1 protein min-1, 10 min) with a biphasic pattern saturating at 30 min
      (bioconcentration factor = 2.7 x 10(3)). 3-(3,4-Dichlorophenyl)-1,1'-dimethyl
      urea (30 microM) reduced the uptake rate by 5% with a corresponding 33% reduction
      in CH3Hg+ accumulation. Dark exposure (24 hr) of cells reduced the CH3Hg+ uptake
      rate (22.3%) accompanied by a considerable decline in the bioconcentration factor
      (1.4 x 10(3)). Of the four permeabilizers used, p-chloromercuribenzoate (1
      microM) proved most effective in altering the CH3Hg+ uptake kinetics while
      dimethyl sulfoxide (5%) and cetyl trimethylammonium bromide (1%) lowered the
      bioconcentration factor to 2.2 x 10(3) and 1.2 x 10(3), respectively. After
      toluene exposure, however, the cells revealed no sign of CH3Hg+ uptake. The data
      have been discussed in light of the role(s) of thiols, photoautotrophy, and
      membrane integrity in regulating the cellular influx of CH3Hg+.

PMID- 8565883
TI  - A dog's tale: soil ingestion by a canine.
AB  - A single Irish Setter pet dog had its soil ingestion behavior quantitatively
      estimated on 3 consecutive days via a soil tracer-based mass-balance methodology.
      The results indicated a high agreement among the eight tracers (Al, Si, Ti, Y,
      Zr, La, Ce, and Nd) employed to estimate soil ingestion. The estimated daily soil
      ingestion rate ranged from approximately 10 to 20 g/day depending on the tracer.
      This represents a value far exceeding soil ingestion reported by an "average"
      child (ranging from 30 to 50 mg/day). The several hundred-fold higher soil
      ingestion rate in this dog compared to soil ingestion by an average child
      suggests the need to evaluate more fully soil and dust ingestion in domestic
      animals and wildlife especially with respect to potential exposure to
      contaminants in soil.

PMID- 8565884
TI  - From single-substance evaluation to ecological process concept: the dilemma of
      processing gold with cyanide.
AB  - In the past decades, limit concentration values for environmentally dangerous
      synthetic and natural chemical substances have been established in industrialized
      countries. Depending on the range of application, state of aggregation,
      propagation velocity, specific action on living organisms, long- or short-time
      effect, etc., different terms are used to specify these limit concentrations
      (acceptable daily intakes, TLV, LD50, emission values, water quality standards,
      etc.). Several parameters (e.g., range of application, ethic and social
      valuation, environmental factors, scientific knowledge) have led to nationally
      and internationally varying values depending on the region and time. The accuracy
      of this system of evaluation cannot necessarily be improved by listing further
      analytical data, but rather by furnishing sufficiently secured scientific data
      for a serious discussion, with the public concepts influenced more and more by
      the mass media. The best-established scientific knowledge has been acquired by
      the chemical industry. National and international groups demand that ecological
      chemical problems in other fields of industry be dealt with as well; this
      research should, without doubt, be intensified. The example of the mining
      industry, which must employ chemical methods to isolate small concentrations
      (ppm), demonstrates the environmental conflict caused by the increasing world
      population, requiring the adaptation of the process by industry to the modern
      environmental concept. This is illustrated by the evolution of the gold recovery
      process.

PMID- 8565885
TI  - Endoscopic ultrasound and endorectal magnetic resonance imaging: a prospective,
      comparative study for preoperative staging and follow-up of rectal cancer.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic ultrasound has become the best available
      method for local staging of primary rectal cancer and diagnosing recurrent local
      disease. The aim of this study is to compare the value of endoscopic ultrasound
      (EUS) to magnetic resonance imaging with an endorectal coil (EMRI). PATIENTS AND
      METHODS: Twenty-one patients (11 women, 10 men, mean age 63 years, range 31-79)
      with primary rectal cancer (n = 6) or follow-up examinations for recurrent local
      disease (n = 15) were investigated by EUS using an echo colonoscope (CF-UM 20,
      Olympus Optical) and by endorectal coil MRI on a 1.5 tesla MR system (General
      Electric). T2-weighted and contrast-enhanced T1-weighted images were obtained.
      The results of preoperative examinations were compared to histopathological
      findings regarding the T staging, with special focus on the transmural tumor
      infiltration. RESULTS: EUS identified all tumors, whereas one tumor was missed by
      EMRI. EUS was superior to EMRI in T staging (accuracy 83%/40%), due to the better
      differentiation between T1 and T2 tumors, as the endorectal coil could not
      differentiate between stage T1 and stage T2. The accuracy of EMRI in assessing
      perirectal infiltration was 80%, compared to EUS with 100%. Local tumor
      recurrence was found in six of 15 patients, without endoscopic signs of recurrent
      disease in four of them. All were detected by EUS. Only one recurrence was missed
      by EMRI. Accuracy and positive and negative predictive values in follow-up
      examinations for recurrent disease for EUS were 93%, 86%, and 100%, and for both
      the T2-weighted and T1-weighted contrast-enhanced sequences of endorectal coil
      MRI, they were 93%, 100%, and 90%, respectively. CONCLUSIONS: Endoscopic
      ultrasound and endorectal coil MRI are comparable methods in the preoperative
      staging and early diagnosis of recurrent rectal cancer. The advantages of EUS are
      the small diameter of the instrument, availability, and lower costs. In contrast,
      EMRI is operator-independent, and may become important for combined local and
      distant staging and follow-up examination in rectal cancer, if contrast-enhanced
      imaging can improve the sensitivity for liver metastases.

PMID- 8565886
TI  - Endoscopic MRI: preliminary results of a new technique for visualization and
      staging of gastrointestinal tumors.
AB  - BACKGROUND AND STUDY AIMS: The principle of endoscopic ultrasonography-
      introducing the transducer of an external imaging method, such as
      ultrasonography, in combination with an endoscope into the gastrointestinal tract
      for higher-resolution imaging--has also been applied to magnetic resonance
      imaging (MRI). We report here on our preliminary experience with a new method of
      endoscopic MRI in the upper gastrointestinal tract. PATIENTS AND METHODS:
      Endoscopic MRI was performed in 32 patients with esophageal (n = 8) or gastric
      diseases (n = 24), mostly tumors (n = 26). Most cancers were at an advanced stage
      (T3/T4). A prototype MRI endoscope connected to a 1.5 tesla MRI scanner was used.
      The accuracy of endoscopic MRI in visualizing and staging gastrointestinal
      lesions was assessed. RESULTS: The normal gastrointestinal wall consisted of
      three layers, and tumors were visualized as having a low signal intensity on both
      T1- and T2-weighted sequences. Destruction of the wall layers was found to be
      characteristic of malignancy. Sufficient images were obtained in seven of eight
      esophageal cases (88%), but in only 14 of 24 gastric cases (58%). In patients in
      whom adequate visualization was achieved, the endoscopic MRI results of local and
      regional staging were consistent with surgical, histopathological, CT and/or EUS
      results in all six esophageal cancer cases and in 89% (T stage) and 56% (N stage)
      of the nine patients with gastric cancer. CONCLUSIONS: These preliminary results
      of endoscopic MRI are the first to be reported in the English literature. They
      show the potential of the method for local and regional staging, three
      dimensional visualization of lesions being a potential advantage. Further
      technical improvements are expected.

PMID- 8565887
TI  - Highly flexible self-expanding meshed metal stents for palliation of malignant
      esophagogastric obstruction.
AB  - BACKGROUND AND STUDY AIMS: Palliative treatment methods for esophageal and
      cardiac cancer include dilation, laser vaporization and other thermal methods,
      alcohol injection, and stent insertion. None of these procedures, however, has
      proved to be a simple, well-tolerated, and lasting method. We present here our
      results with a new, highly flexible self-expanding metal stent made of nitinol,
      which is considered to be particularly useful for difficult (long and tortuous)
      malignant strictures. PATIENTS AND METHODS: From November 1991 to December 1994,
      114 patients with unresectable esophagogastric malignancies or tumor recurrences
      (92 men, 22 women, mean age 64 years) were treated using 138 highly flexible
      meshed self-expanding metal stents. Regular clinical and endoscopic follow-up was
      performed, and stent obstruction or overgrowth was treated by argon plasma
      coagulation (APC). Patients were followed up until death (n = 78; average follow
      up 17 weeks, range 1-90 weeks). Thirty-six patients were alive in December 1994
      and had had an average of 20 weeks of follow-up (range 1-160 weeks). RESULTS:
      Stent insertion was technically successful in 97% of cases, and led to a
      reduction of dysphagia (graded 0-4) from a mean score of 3.5 to a mean score of
      1.5. Preparatory treatment to open tight strictures was necessary in 80% of
      cases. Balloon dilation to support stent expansion was carried out in 42 patients
      (37%). During follow-up, tumor ingrowth occurred in 66% of cases after a mean of
      seven weeks, and was successfully treated by APC. Including preparatory treatment
      and re-treatment, patients underwent a mean of 3.5 endoscopic procedures (range 1
      12 procedures), which led to good clinical success in 73% of cases. Ninety-six
      percent of the patients continued to be able to swallow (dysphagia score < or =
      2) during follow-up. CONCLUSIONS: Highly elastic self-expanding metal stents can
      be successfully implanted in the majority of patients, particularly in those with
      difficult malignant strictures not easily amenable to other methods. The devices
      provide good palliation with effective relief of dysphagia, easy handling and
      implantation, and offer a satisfactory quality of life to the patient. However,
      tumor ingrowth is a significant problem, even though it can be successfully
      managed by APC. Adequate covering of the stent that does not affect its
      mechanical properties or firm anchoring should solve at least some of these
      problems.

PMID- 8565888
TI  - Gianturco-Z stents in the palliative treatment of malignant esophageal
      obstruction and esophagotracheal fistulas.
AB  - BACKGROUND AND STUDY AIMS: The palliative endoscopic treatment of malignant
      obstruction of the upper gastrointestinal tract, including esophagorespiratory
      fistulas, is often difficult. The efficacy of polyethylene-coated [corrected]
      Gianturco-Z stents in these sometimes complicated tumor stenoses was
      investigated. PATIENTS AND METHODS: Twenty patients with malignant obstruction of
      the esophagus and the cardia, including six patients with esophagotracheal
      fistulas, were treated with Gianturco-Z stents. Five patients had previously been
      provided with another type of self-expanding metal endoprosthesis (two with
      Wallstents and three with Ultra-flex memory metal stents), and needed retreatment
      because of tumor ingrowth or overgrowth, esophagotracheal fistulas, or
      insufficient stent expansion. All data acquired prior to and during stent
      implantation, as well as during the follow-up period, were recorded
      prospectively. RESULTS: No technical problems occurred during the implantation of
      the stents. Nineteen of 20 Gianturco-Z stents (95%) spontaneously showed
      sufficient expansion at the endoscopic control, which was conducted within the
      following 48 hours. All patients, with the exception of one, reported immediate
      improvement of their dysphagia. The sealing of the six fistulas was also
      achieved. Severe early complications, such as bleeding or perforation, did not
      occur, but one stent migration was encountered. Two types of minor problems were
      observed: short-term retrosternal and epigastric pain (11 patients) and formation
      of a pouch at the upper rim of the stent (one patient). In the follow-up, tumor
      overgrowth of the stent ends was found in one patient, who was retreated with
      electrocoagulation. Tumor infiltration of the wire mesh has not been observed so
      far. In one patient, dislocation of a stent into the stomach occurred (probably
      as a result of endoscopic measures being performed to control tumor bleeding).
      CONCLUSIONS: We conclude that the treatment of malignant esophageal obstructions,
      including esophagorespiratory fistulas, with Gianturco-Z stents is effective, and
      that implantation is safe, especially in the case of tumor stenoses in the
      proximal esophagus. The expansile force of the stent is sufficient even for very
      firm strictures; and the polyethylene [corrected] covering of the stent seems to
      prevent tumor ingrowth.

PMID- 8565889
TI  - Metal stents for palliation of rectal carcinoma: a preliminary report on 12
      patients.
AB  - BACKGROUND AND STUDY AIMS: Laser therapy is often the only alternative to
      palliative surgery for elderly patients with advanced rectal carcinoma. In order
      to reduce the number of laser sessions required, we tried to insert metal stents
      after initial relief of the obstruction. PATIENTS AND METHODS: In 12 patients
      (seven female, five male, aged 77-91 years) with rectal or rectosigmoid
      carcinomas, metallic self-expanding stents (length 5-10 cm, internal diameter 1-2
      cm) were introduced. Initial treatments were performed with Nd:YAG laser (mean
      number of sessions 3.1) in order to allow free passage of an adult colonoscope.
      Endoscopic and clinical follow-up was carried out at regular intervals. RESULTS:
      Stent insertion was possible in 11 of the 12 patients. Failure occurred in one
      patient with sigmoid carcinoma with a distorted loop and diverticulosis. In three
      patients, the prostheses migrated due to the opening of the lumen being too
      large; after stent removal, a second stent was successfully placed. Seven
      patients have died since the beginning of the study, all from the initial
      disease, without symptoms of stent occlusion. Stenting allowed the number of
      laser sessions to be reduced. The interval between the laser sessions was
      extended from 5.1 weeks in a historical control group of 65 patients to the 9.7
      weeks in these 11 patients with additional stenting. CONCLUSION: Stenting for
      rectal carcinoma is technically feasible and safe, and probably reduces the
      number of laser sessions required. However, better materials are required.

PMID- 8565890
TI  - Results of the new nitinol self-expandable stents for distal biliary structures.
AB  - BACKGROUND AND STUDY AIMS: The nitinol stent is a self-expandable spiral stent
      made of nickel-titanium alloy. We performed a pilot study to evaluate the method
      of stent insertion and stent efficacy. PATIENTS AND METHODS: Twenty-eight
      patients with irresectable malignancy had nitinol stents inserted for obstructive
      jaundice due to distal biliary strictures. They were followed prospectively for a
      median of ten weeks (range 1-48) until stent occlusion or death. All patients
      underwent sphincterotomy prior to stent insertion. Stent deployment was assisted
      by subsequent balloon dilation of the stent in two patients. Plastic stent
      insertion was used to temporarily brace the nitinol stent in another three
      patients. RESULTS: Short-term relief of jaundice was achieved in 20 of the 28
      patients (71%). The remaining eight patients had persistent jaundice due to
      failure of stent insertion (three patients) or early stent dysfunction (five
      patients). Long-term success was achieved in 12 of 28 patients (43%). Ten of the
      12 patients died without complications after a median of 13.5 weeks (range 3-48).
      One of the 12 patients is still alive with the stent in place for 40 weeks, and
      one patient underwent elective bypass surgery, and the stent was removed
      surgically. Eight of the 28 patients had recurrent symptoms due to late stent
      dysfunction after a median of 19 weeks (range 6-32). CONCLUSIONS: Nitinol stents
      are technically difficult to insert. The problem of stent dysfunction (13 of 28,
      46%) is not improved by the use of nitinol stents. Whether improvement of the
      insertion technique and enhancement of the expanding force of the stent may
      improve stent efficacy merits further evaluation.

PMID- 8565891
TI  - Esophageal cancer: which stent, who places it, and where?

PMID- 8565892
TI  - New EU regulations in endoscopy.
AB  - As a result of European unification, new regulations valid within the territory
      of the European Union (EU) have been negotiated and published. As in other
      medical fields, the Medical Device Directive (MDD) is the most important new
      regulation and also effects endoscopy. In a transition period until June 1998,
      the MDD will be transposed into national law by the member states of the EU.
      Compliance with the MDD and other European regulations is indicated by the CE
      mark affixed to the product.

PMID- 8565893
TI  - DDW Congress Report 1995 San Diego, 14-17 May 1995.
AB  - This year's DDW again presented us with an extremely interesting and very up-to
      date variety of endoscopic abstracts, dealing with established as well as new
      technology, and increasingly attempting to evaluate relevant issues such as cost
      effectiveness and outcome. As is the case every year, the present DDW Congress
      Report faces the problem of how to cover all the abstracts accepted, while at the
      same time trying not to deal with them too superficially. The published
      endoscopic abstracts, the number of which has greatly increased, form the basis
      for this review, although an update for oral or poster presentation in San Diego
      may have changed the message in a few of them.

PMID- 8565894
TI  - Endoscopic and related abstracts of the 4th United European Gastroenterology
      Week. Berlin, 17-21 September 1995.

PMID- 8565895
TI  - In situ bioremediation of chlorinated solvents.
AB  - Chlorinated solvents and their natural transformation products are the most
      frequently observed groundwater contaminants in the United States. In situ
      bioremediation using anaerobic or aerobic co-metabolic processes is a promising
      means of cleaning up contaminated aquifers. Studies show that under natural
      conditions trichloroethylene can be anaerobically degraded to dichloroethylene,
      vinyl chloride, and ethylene. Pilot scale field studies of in situ aerobic co
      metabolic transformations have shown that indigenous microbes grown on phenol are
      more effective at degrading trichloroethylene and cis-1,2-dichloroethylene than
      microbes grown on methane. Modeling studies support field observations and
      indicate that the removal of trichloroethylene and cis-dichloroethylene results
      from the biostimulation of an indigenous microbial population. Field tests and
      modeling studies indicate that, at high TCE concentration, degradation becomes
      stoichiometrically limited.

PMID- 8565896
TI  - Natural selection of PAH-degrading bacterial guilds at coal-tar disposal sites.
AB  - Microbial activity patterns at buried coal-tar disposal sites have been under
      investigation for several years to determine the response of naturally occurring
      microflora to polycyclic aromatic hydrocarbons (PAHs) at the sites. At one site
      in upstate New York, data have shown enrichment of PAH-degrading bacteria in
      subsurface contaminated zones but not in uncontaminated zones. Similar work at a
      midwestern site showed that the same trends existed in a heterogeneous disposal
      site except that a borehole outside the plume showed some PAH-mineralization
      activity. Polymerase chain reaction amplification of DNA extracted from sediment
      samples from the New York site indicated the presence of naphthalene metabolism
      genes nahAc and nahR, similar to those found on the NAH7 plasmid of Pseudomonas
      putida G7. Significant sequence polymorphism was observed in amplified nahAc
      products, indicating that divergent homologs of nahAc were present in the native
      community. Protozoan numbers were elevated in sediment samples displaying
      relatively high PAH-degrading activity, suggesting that a food chain was
      established based on PAH-degrading bacteria. Removal of the coal-tar source at
      the site occurred in 1991. In 1992, sampling of three key borehole stations
      revealed that mixing and backfilling operations had introduced soil
      microorganisms into the source area and introduced 14C-PAH-mineralization
      activity into the previously inactive pristine area. Thus removal of the source
      of the contaminants and restoration at the site have altered the microbial
      activity patterns outside the contaminant plume as well as in the source area.

PMID- 8565897
TI  - Plasmid transfer for enhancing degradation capabilities.
AB  - The kinetics of plasmid conjugation for the TOL and RP4 plasmids depend strongly
      on the donor cells' specific growth rate and substrate concentration, both of
      which determine the cells' energy availability. Although transfer rates can be
      large when energy availability is high, normal biological processes have low
      energy availability. Therefore, we propose and evaluate preliminarily a simple
      scheme to create a small zone of high energy availability.

PMID- 8565898
TI  - Tracking microbial populations effective in reducing exposure.
AB  - Microbial ecology provides the link between basic biochemical and molecular
      studies on toxicity reduction by microbial metabolism and environmental studies
      that determine exposure. This link provides the ability to determine which
      microorganisms are responsible for the actual transformations in nature, thereby
      establishing how predictive the laboratory pathway, kinetic, regulatory, and
      enzyme mechanistic information is for nature. This information can be important
      to the rate of toxicant removal, the type and concentration of intermediate
      product(s), and the identification of conditions that limit effective toxicant
      removal. Nucleic acid-based methods now provide the main means to track important
      biodegrading populations. Examples of these methods are given that illustrate
      tracking a biodegrading microbe injected into an aquifer, following community
      succession in a toluene-degrading fluidized bed reactor, aiding the isolation
      from nature of novel biodegrading organisms, and rapidly characterizing the
      extent of microbial diversity in an aquifer stimulated to co-metabolize
      trichloroethene.

PMID- 8565899
TI  - A small circle of knowledge, a large circle of ignorance.

PMID- 8565900
TI  - The role of plants and plant/microbial systems in the reduction of exposure.
AB  - The activities of plants and plant/microbial associations may offer a viable
      means of accomplishing the in situ remediation of contaminated soils. Two uses of
      plants for phytoremediation are reported here. In one set of studies, the ability
      of plants to foster degradative microorganisms was investigated. Results
      indicated that the degradation of several chlorinated pesticides increased in
      rhizosphere soil and that this same increase occurred when unplanted soils were
      given materials released from plant roots. In current investigations, the
      potential for plants to remove and accumulate metals from their environment is
      being considered. This work employs a unique testing system, the target-neighbor
      method, that allows evaluation of how planting density influences metal uptake.
      Results of these studies could provide the information needed to manipulate plant
      density for optimization of metal removal (remediation of metal-contaminated
      soil) or minimization of the amount of toxic metals in important crops (reduction
      of human exposure).

PMID- 8565901
TI  - Reduction of azo dyes and nitroaromatic compounds by bacterial enzymes from the
      human intestinal tract.
AB  - Several anaerobic bacteria from the human intestinal tract are capable of
      reducing azo dyes and nitropolycyclic aromatic hydrocarbons to the corresponding
      aromatic amines with enzymes that have azoreductase and nitroreductase
      activities. The majority of bacteria with these activities belong to the genera
      Clostridium and Eubacterium. The azoreductases and nitroreductases from three
      Clostridium strains and one Eubacterium strain were studied. Both enzymes were
      produced constitutively in each of the bacteria; the enzymes from various
      bacteria had different electrophoretic mobilities. The azoreductases from all of
      the bacteria had immunological homology, as was evident from the cross-reactivity
      of an antibody raised against the azoreductase of C. perfringens with
      azoreductases from other bacteria. Comparison of azoreductases and
      nitroreductases showed that they both had identical electrophoretic mobilities on
      polyacrylamide gels and reacted with the antibody against the azoreductase from
      C. perfringens. Furthermore, the nitroaromatic compounds competitively inhibited
      the azoreductase activity. The data indicate that the reduction of both
      nitroaromatic compounds and azo dyes may be carried out by the same enzyme, which
      is possibly a flavin adenine dinucleotide dehydrogenase that is synthesized
      throughout the cell and not associated with any organized subcellular structure.

PMID- 8565902
TI  - Biochemistry and genetics of PCB metabolism.
AB  - Biphenyl(BP)-utilizing bacteria, which include both Gram-negative and Gram
      positive strains, are ubiquitously distributed in the environment. These bacteria
      co-metabolically degrade a variety of polychlorinated biphenyl (PCB) congeners to
      the corresponding chlorobenzoic acids through 2,3-dioxygenation. Certain strains
      degrade even highly chlorinated PCBs through 3,4-dioxygenation. The ring meta
      cleavage dioxygenase purified from Pseudomonas pseudoalcaligenes KF707 is a homo
      octamer containing ferrous ions as the essential cofactor. Transposon mutants
      revealed that the bph-encoded enzymes possess a wide range of substrate
      specificity for various aromatic hydrocarbons. The bphABCXD gene cluster coding
      for the degradation of PCBs to chlorobenzoic acids was first cloned from P.
      pseudocaligenes KF707 and sequenced and then was cloned from a number of BP
      utilizing strains and sequenced. Some strains possess a bph operon that is very
      similar, if not identical, to that of KF707. Some bph genes share homologies with
      different degrees. Deletion and shuffling of bph genes are also found.

PMID- 8565903
TI  - Cytochrome P450 proteins and potential utilization in biodegradation.
AB  - The cytochrome P450 enzymes are major catalysts involved in the oxidations of
      xenobiotic chemicals in microorganisms as well as higher animals and plants.
      Because of their functional roles, they offer potential in biodegradation
      technology. A number of microbial P450s have already been characterized and offer
      advantages in terms of their high catalytic rates and facile expression in
      microorganisms. One approach to extending the catalytic selectivity to more
      compounds in the environment is rational design. In three cases, the three
      dimensional structures of bacterial cytochrome P450 enzymes are available and can
      be further understood through studies with molecular dynamics. Many mammalian
      cytochrome P450 enzymes have been studied extensively and have potential for
      biodegradation because of their broad catalytic selectivities (e.g., P450 2E1).
      Several advances have been made in the heterologous expression of these proteins
      in microorganisms. Improvements under development include electron transfer from
      flavodoxin and the use of cytochrome P450:NADPH-cytochrome P450 reductase fusion
      proteins. Random mutagenesis offers the potential of improving the catalytic
      activities of some of these proteins. Future challenges include the use of
      cytochrome P450 expression vectors in microorganisms capable of thriving in the
      environment; recent success in expression of vectors in Salmonella genotoxicity
      tester strains may be encouraging in this regard.

PMID- 8565904
TI  - Genetic adaptation of bacteria to halogenated aliphatic compounds.
AB  - The bacterial degradation and detoxification of chlorinated xenobiotic compounds
      requires the production of enzymes that are capable of recognizing and converting
      compounds which do not occur at significant concentrations in nature. We have
      studied the catabolic route of 1,2-dichloroethane as an example of a pathway for
      the conversion of such a synthetic compound. In strains of Xanthobacter and
      Ancylobacter that have been isolated on 1,2-dichloroethane, the first catabolic
      step is catalyzed by a hydrolytic haloalkane dehalogenase. The enzyme converts
      1,2-dichloroethane to 2-chloroethanol but is also active with many other
      environmentally important haloalkanes such as methylchloride, methylbromide, 1,2
      dibromoethane, epichlorohydrin, and 1,3-dichloropropene. Further degradation of 2
      chloroethanol proceeds by oxidation to the carboxylic acid and dehalogenation to
      glycolate. The aldehyde dehydrogenase prevents toxicity of the reactive
      chloroacetaldehyde that is formed as an intermediate and is necessary for
      establishing a functional 2-chloroethanol degradative pathway in a strain that is
      not capable of growth on this compound.

PMID- 8565905
TI  - Biodegradation: its role in reducing toxicity and exposure to environmental
      contaminants.

PMID- 8565906
TI  - Bacterial growth with chlorinated methanes.
AB  - Chlorinated methanes are important industrial chemicals and significant
      environmental pollutants. While the highly chlorinated methanes, trichloromethane
      and tetrachloromethane, are not productively metabolized by bacteria,
      chloromethane and dichloromethane are used by both aerobic and anaerobic
      methylotrophic bacteria as carbon and energy sources. Some of the dehalogenation
      reactions involved in the utilization of the latter two compounds have been
      elucidated. In a strictly anaerobic acetogenic bacterium growing with
      chloromethane, an inducible enzyme forming methyltetrahydrofolate and chloride
      from chloromethane and tetrahydrofolate catalyzes dehalogenation of the growth
      substrate. A different mechanism for the nucleophilic displacement of chloride is
      observed in aerobic methylotrophic bacteria utilizing dichloromethane as the sole
      carbon and energy source. These organisms possess the enzyme dichloromethane
      dehalogenase which, in a glutathione-dependent reaction, converts dichloromethane
      to inorganic chloride and formaldehyde, a central metabolite of methylotrophic
      growth. Sequence comparisons have shown that bacterial dichloromethane
      dehalogenases belong to the glutathione S-transferase enzyme family, and within
      this family to class Theta. The dehalogenation reactions underlying aerobic
      utilization of chloromethane by a pure culture and anaerobic growth with
      dichloromethane by an acetogenic mixed culture are not known. It appears that
      they are based on mechanisms other than nucleophilic attack by tetrahydrofolate
      or glutathione.

PMID- 8565907
TI  - Characterization of the first enzyme in 2,4-dichlorophenoxyacetic acid
      metabolism.
AB  - This paper reviews the properties of the Alcaligenes eutrophus JMP134 tfdA gene
      product, the enzyme responsible for the first step in 2,4-dichlorophenoxyacetic
      acid (2,4-D) biodegradation. The gene was overexpressed in Escherichia coli and
      several of its enzymatic properties were characterized. Although this enzyme
      catalyzes a hydroxylation reaction, it is not a monooxygenase. Rather, TfdA is an
      Fe(II) and alpha-ketoglutarate-dependent dioxygenase that metabolizes the latter
      cosubstrate to succinate and carbon dioxide. A variety of other phenoxyacetates
      and alpha-ketoacids can be used by the enzyme, but the greatest catalytic
      efficiencies were found using 2,4-D and alpha-ketoglutarate. The enzyme possesses
      multiple essential histidine residues, whereas catalytically essential cysteine
      and lysine groups do not appear to be present.

PMID- 8565908
TI  - Mechanisms for polycyclic aromatic hydrocarbon degradation by ligninolytic fungi.
AB  - Ligninolytic fungi accomplish the partial degradation of numerous aromatic
      organopollutants. Their ability to degrade polycyclic aromatic hydrocarbons
      (PAHs) is particularly interesting because eukaryotes were previously considered
      to be unable to cleave fused-ring aromatics. Recent results indicate that
      extracellular peroxidases of these fungi are responsible for the initial
      oxidation of PAHs. Fungal lignin peroxidases oxidize certain PAHs directly,
      whereas fungal manganese peroxidases co-oxidize them indirectly during enzyme
      mediated lipid peroxidation.

PMID- 8565909
TI  - Recruitment of co-metabolic enzymes for environmental detoxification of
      organohalides.
AB  - Polyhalogenated compounds are often environmentally persistent and toxic to
      mammals. Microorganisms that metabolize these compounds can detoxify contaminated
      environments. Different biochemical mechanisms are used to metabolize
      polyhalogenated compounds, but few naturally occurring bacteria have this
      capability. A recombinant bacterium was constructed to metabolize polyhalogenated
      compounds to nonhalogenated end products. Seven genes were expressed in
      Pseudomonas putida G786 to biosynthesize cytochrome P450CAM and toluene
      dioxygenase. Cytochrome P450CAM catalyzed reductive dechlorinated reactions and
      toluene dioxygenase catalyzed oxidative dechlorination. With pentachloroethane,
      reductive dechlorination yielded trichloroethylene, which was further oxidized to
      formate and glyoxylate. The sequential action of cytochrome P450CAM and toluene
      dioxygenase with polyhalogenated compounds constitutes a novel engineered
      metabolic pathway.

PMID- 8565910
TI  - Physiological attributes of microbial BTEX degradation in oxygen-limited
      environments.
AB  - Our work has focused on the determination of physiological traits that may
      facilitate in situ degradation of xenobiotic compounds by indigenous
      microorganisms. For this our interests center on the following questions: What
      are the ambient conditions in a benzene, toluene, ethylbenzene, and xylene (BTEX)
      contaminated aquifer? What is the behavior of indigenous bacteria under these
      conditions? What are the attributes of bacterial strains that are functional
      under hypoxic conditions? How do these strains compare with other BTEX-degrading
      strains?

PMID- 8565911
TI  - Reductive dechlorination of tetrachloroethene by a high rate anaerobic microbial
      consortium.
AB  - Tetrachloroethene (PCE) and other chloroethenes are major contaminants in
      groundwater, and PCE is particularly resistant to attack by aerobes. We have
      developed an anaerobic enrichment culture that carries out reductive
      dechlorination of chloroethenes to ethene at high rates, thereby detoxifying
      them. Although the electron donor added to the culture is methanol, our evidence
      indicates that H2 is the electron donor used directly for dechlorination. We have
      recently obtained a culture from 10(-6) dilution of the original methanol/PCE
      culture that uses H2 as an electron donor for PCE dechlorination. Because the
      culture can be transferred indefinitely and the rate of PCE dechlorination
      increases after inoculation, we suggest that dechlorinating organisms in the
      culture use the carbon-chlorine bonds in chloroethenes as electron acceptors for
      energy conservation.

PMID- 8565912
TI  - Modeling organic chemical fate in aquatic systems: significance of
      bioaccumulation and relevant time-space scales.
AB  - The importance of aquatic food chain bioaccumulation of organic chemicals in
      contributing to human dose is derived. It is shown that for chemicals with log
      octanol water partition coefficients greater than about 3, the role of food chain
      transfer to fish consumed by humans becomes the more dominant route over drinking
      water. Modeling of aquatic food chain bioaccumulation then becomes necessary to
      accurately estimate dose of such chemicals to humans. The relevant time and space
      scales for groundwater and surface water also indicate a division of organic
      chemicals at a log octanol water partition coefficient of about 3. For chemicals
      greater than that level, groundwater transport is minimal, while for chemicals
      with log octanol water coefficients of less than about 3, detention times are
      long relative to surface water and biodegradation processes become more
      significant. An illustration is given of modeling the groundwater transport of
      two organic chemicals (BCEE and benzene) and a metal (chromium) at a Superfund
      site. The model indicates that after 10 years only a relatively small fraction of
      the chemicals had traveled in the groundwater about 300 m to the point of release
      from the site to surface water. On the other hand, steady state in the adjacent
      stream and lake is reached rapidly over a distance of 2000 m, illustrating the
      difference in spatial and temporal scales for the groundwater and surface water.

PMID- 8565913
TI  - Mechanisms of degradation by white rot fungi.
AB  - White rot fungi use a variety of mechanisms to accomplish the complete
      degradation of lignin and a wide variety of environmental pollutants. Both
      oxidative and reductive reactions are required for the metabolism of both lignin
      and environmental pollutants. The fungi secrete a family of peroxidases to
      catalyze both direct and indirect oxidation of chemicals. The peroxidases can
      also catalyze reductions using electron donors to generate reductive radicals. A
      cell-surface membrane potential can also be used to reduce chemicals such as TNT.

PMID- 8565914
TI  - Organic halogens in the environment: studies of environmental biodegradability
      and human exposure.
AB  - Organic halogens from chlorobleaching of kraft pulp were not as biorecalcitrant
      as has been assumed. Fifty percent were removed during biotreatment of
      wastewater, and 50% of the remaining organohalogens faded in fresh water
      ecosystems in 200 to 400 days. Molecular size seemed not to hinder biodegradation
      up to sizes of approximately 2000 daltons. Anoxic biodegradation was of prime
      importance for halomineralization of pulp bleaching organohalogens but could also
      lead to toxic metabolites such as vinyl chloride from tri- and tetrachloroethene
      in anoxic soil. Indigenous soil microbes were unable to clean old organohalogen
      pollution but had converted chlorophenols into polymeric substances, chlorohumus,
      which were found bioaccumulable by earthworms in spite of the large (up to 5000
      g/mole) molecular sizes. Because of the danger of formation of toxic metabolites,
      the biochemistry of the xenobiotic degradation must be elucidated before active
      bioremediation is practiced on polluted soil or water. Groundwater pollution by
      chlorophenols led to increased disease among the exposed population in one well
      studied case. Two further cases of potential environmental health impact are
      described.

PMID- 8565915
TI  - Interactions of aniline with soil and groundwater at an industrial spill site.
AB  - The interactions of aniline with soil at an industrial spill site were
      investigated. Sorption of aniline to the soil was observed to occur through a two
      step mechanism. The first step was an ion exchange process with the protonated
      amine serving as an organic cation. This step was influenced by solution pH and
      ionic composition. The second step was covalent bonding most likely with quinone
      moieties and oxidation with polymerization of aniline. The extent of covalent
      bonding was influenced by the presence of oxygen and redox potential. The
      majority of aniline that was bound to the soil did not readily desorb under a
      variety of abiotic conditions. However, aniline was released to a significant
      extent in the presence of denitrifying and methanogenic microbial activity.
      Aniline in aqueous solution was readily biodegradable under aerobic and
      denitrifying conditions. Soil-bound aniline was observed not to be biodegradable.
      This paper provides an overview of results.

PMID- 8565916
TI  - Coupling transport and biodegradation of VOCs in surface and subsurface soils.
AB  - Volatile organic chemicals present at Superfund sites preferentially partition
      into the soil gas and may be available for microbial degradation. A simple mass
      transfer model for biodegradation for volatile substrates has been developed for
      the aerobic decomposition of aromatic and aliphatic hydrocarbons. The mass
      transfer analysis calculates diffusive fluxes from soil gas through water and
      membrane films and into the cell. This model predicts an extreme sensitivity of
      potential biodegradation rates to the air-water partition coefficients of the
      compounds. Aromatic hydrocarbons are removed rapidly while the aliphatic
      hydrocarbons are much slower by orders of magnitude. Furthermore, oxygen transfer
      is likely to limit aromatic hydrocarbon degradation rates. The model presents
      results that cast doubt on the practicality of using methane or propane for the
      co-metabolic destruction of trichloroethylene in a gas phase bioreactor. Toluene
      as a primary substrate has better mass transfer characteristics to achieve more
      efficient trichloroethylene degradation. Hence, in sites where these contaminants
      coexist, bioremediation could be improved.

PMID- 8565917
TI  - Fossil fuel biodegradation: laboratory studies.
AB  - Biodegradation of the polycyclic aromatic hydrocarbons of creosote by undefined
      bacterial cultures was shown to be accompanied by the accumulation of neutral and
      acidic oxidation products. Formation of a number of identified neutral products
      is accounted for by demonstration of anomalous actions of an arene dioxygenase on
      the benzylic methylene and methylene carbons of napthenoaromatic hydrocarbons.
      Both neutral and acidic water-soluble fractions are also formed when various
      mixed bacterial cultures degrade weathered crude oil. While constituents of these
      fractions are not yet identified, the neutral materials have been shown to be
      toxic to developing embryos of invertebrates. These observations are discussed in
      relation to chemical and toxicological assessments of biodegradation of the
      complex chemical mixtures of fossil fuels.

PMID- 8565918
TI  - Mathematical modeling of BTX: biotransformation and transport in the subsurface.
AB  - A two-dimensional compositional model is presented; this model describes the
      transport and biotransformation of organic contaminants in a variably saturated
      subsurface environment. Modeled processes included mass exchange between
      constituent phases (water, air, soil, and organisms), advective and dispersive
      fluxes in the water phase, diffusive flux in the air phase, and biotransformation
      and biomass production in the biophase. In this model, solute transfer across
      air/water and water/solid interfaces is modeled using equilibrium relationships.
      Rate-limited mass transfer between the water and biophases is described with a
      linear driving force expression. Microbial degradation and biomass net growth are
      modeled by Monod-type kinetics. Solute transport and microbial growth equations
      are solved using an iterative Galerkin finite element method with a variable time
      weighting scheme. Coupled biophase mass balance equations for each component are
      solved with a Newton-Raphson iterative scheme. Model capabilities are illustrated
      with two-dimensional, cross-sectional simulations of natural bioattenuation. The
      influence of biotransformation processes on the transport and extent of a toluene
      plume is examined.

PMID- 8565919
TI  - Reductive dehalogenation of bromoform in aqueous solution.
AB  - The hybrid semiconducter-macrocycle catalyst TiO2-cobalt phthalocyanine promotes
      the solar photolysis of aqueous bromoform under anaerobic conditions. The major
      decomposition products are dibromoethane and HBr. Bromomethane and methane were
      produced only after prolonged photolysis (30 hr). Acetone, derived from added 2
      propanol, was the only observed oxidation product. Preliminary experiments showed
      that electrolytic reduction of aqueous carbon tetrachloride at a vitamin B12
      modified silver electrode produced the expected lower homologues but with
      surprisingly high yields of methane.

PMID- 8565921
TI  - Biodegradation of sorbed chemicals in soil.
AB  - Rates of biodegradation of sorbed chemicals are usually lower in soil than in
      aqueous systems, in part because sorption reduces the availability of the
      chemical to microorganisms. Biodegradation, sorption, and diffusion occur
      simultaneously and are tightly coupled. In soil, the rate of biodegradation is a
      function of a chemical's diffusion coefficient, sorption partition coefficient,
      the distance it must diffuse from the site of sorption to microbial populations
      that can degrade it, and its biodegradation rate constant. A model (DSB model)
      was developed that describes biodegradation of chemicals limited in the
      availability by sorption and diffusion. Different kinetics expressions describe
      biodegradation depending on whether the reaction is controlled by mass transfer
      (diffusion and sorption) or the intrinsic biodegradation rate, and whether
      biodegradation begins during or after the majority of sorption has occurred. We
      tested the hypothesis that there is a direct relationship between how strongly a
      chemical is sorbed and the chemical's biodegradation rate. In six soils with
      different organic carbon contents, there was no relationship between the extent
      or rate of biodegradation and the sorption partition coefficient for
      phenanthrene. Aging of phenanthrene residues in soil led to a substantial
      reduction in the rate of biodegradation compared to biodegradation rates of
      recently added phenanthrene. Considerable research has focused on identification
      and development of techniques for enhancing in situ biodegradation of sorbed
      chemicals. Development of such techniques, especially those involving inoculation
      with microbial strains, should consider physical mass transfer limitations and
      potential decreases in bioavailability over time.

PMID- 8565920
TI  - Molecular analysis of isophthalate and terephthalate degradation by Comamonas
      testosteroni YZW-D.
AB  - Comamonas testosteroni YZW-D was isolated from Passaic River sediment for its
      ability to degrade isophthalate and terephthalate. Degradation of the two
      isomeric compounds proceeds via separately inducible catabolic pathways that
      converge at protocatechuate. Analysis of the catabolic pathways by which these
      two isomers are degraded demonstrated that a cis-dihydrodiol intermediate is
      involved in both pathways. The genes for the conversion of isophthalate and
      terephthalate to protocatechuate were cloned on a single fragment of genomic DNA
      from C. testosteroni YZW-D. The two operons were located by subcloning and mutant
      complementation experiments. The regions coding for the two degradative pathways
      were sequenced. Analysis of the nucleotide sequence for the isophthalate
      degradation operon located genes for a dioxygenase, a transport protein, a cis
      dihydrodiol dehydrogenase, and a reductase. Analysis of the nucleotide sequence
      for the terephthalate degradation operon located genes for a regulatory protein,
      a transport protein, a dioxygenase large subunit, a dioxygenase small subunit, a
      cis-dihydrodiol dehydrogenase, and a reductase.

PMID- 8565922
TI  - Aerobic and anaerobic PCB biodegradation in the environment.
AB  - Studies have identified two distinct biological processes capable of
      biotransforming polychlorinated biphenyls (PCBs): aerobic oxidative processes and
      anaerobic reductive processes. It is now known that these two complementary
      activities are occurring naturally in the environment. Anaerobic PCB
      dechlorination, responsible for the conversion of highly chlorinated PCBs to
      lightly chlorinated ortho-enriched congeners, has been documented extensively in
      the Hudson River and has been observed at many other sites throughout the world.
      The products from this anaerobic process are readily degradable by a wide range
      of aerobic bacteria, and it has now been shown that this process is occurring in
      surficial sediments in the Hudson River. The widespread anaerobic dechlorination
      of PCBs that has been observed in many river and marine sediments results in
      reduction of both the potential risk from and potential exposure to PCBs. The
      reductions in potential risk include reduced dioxinlike toxicity and reduced
      carcinogenicity. The reduced PCB exposure realized upon dechlorination is
      manifested by reduced bioaccumulation in the food chain and by the increased
      anaerobic degradability of these products.

PMID- 8565923
TI  - Health psychology and public policy: the political process.
AB  - During the past 20 years, psychologists have successfully modified federal
      statutes, resulting in recognition of the profession's clinical and research
      expertise. Despite these successes, professional psychology's training
      institutions have largely failed to address basic issues in health policy and the
      implications of national health policy for psychology. The importance of public
      health programs under Title VII of the Public Health Act and the significance of
      full inclusion of psychology in all federal health programs, including Titles
      XVIII (Medicare) and XIX (Medicaid), are poorly understood by most health
      psychologists. Federal health policy decisions, including management of excessive
      federal health spending, will dictate the growth and opportunities for health
      psychologists. Understanding federal health spending and recent federal
      initiatives such as Resource Based Relative Value Scale, Diagnostic Related
      Groups, and practice guidelines will be of benefit to health psychologists.

PMID- 8565924
TI  - A historical analysis of tobacco marketing and the uptake of smoking by youth in
      the United States: 1890-1977.
AB  - This article presents evidence for sex-specific temporal associations between
      major cigarette marketing campaigns and increases in youth smoking initiation
      using national survey data for 1910-1977 (N = 165,876). Considerable smoking
      initiation occurred in males under 18 and born before 1890 when marketing focused
      only on males. Initiation in male youth increased greatly during 1910-1919; in
      1912, R.J. Reynolds launched its unprecedented campaign for Camel brand.
      Initiation in female youth began in the mid-1920s, coincident with the
      Chesterfield and Lucky Strike women's marketing campaigns. In the late 1960s,
      smoking uptake among young females again increased rapidly, coincident with large
      scale marketing of women's brands. Male initiation did not increase with these
      campaigns. Thus, in each instance, major marketing impact occurred in youth
      smoking initiation only in the sex group targeted.

PMID- 8565925
TI  - Behavioral medicine, clinical health psychology, and cost offset.
AB  - The use of medical services is a function of several interacting psychological
      and social variables as well as a function of physical malfunction. The clinical
      significance of addressing patients' psychosocial issues has only occasionally
      been considered. However, the shift in health care economics toward health care
      maintenance is responsible for the increased interest in interventions in the
      domain of behavioral medicine and health psychology. Evidence is reviewed for 6
      mechanistic pathways by which behavioral interventions can maximize clinical care
      and result in significant economic benefits. The rationale for further
      integration of behavioral and biomedicine interventions is also reviewed.

PMID- 8565926
TI  - The changing workforce: the role of health psychology.
AB  - Because the federal government is the largest payer of all health costs,
      unbridled increases in the health workforce have profound fiscal implications.
      Recent efforts to control health spending through modifications of health
      delivery systems are related to the consequences of the unlimited production of
      health professionals. However, the federal government has established processes
      to review physician workforce changes, and these mechanisms have become important
      in accessing federal training monies. Psychologists have no concerted workforce
      policy and receive little federal training money. Moreover, other health
      professionals have attained statutory authority to perform and provide the same
      services as psychologists. This diffusion of professional functions impedes the
      ability to assess the status of the workforce and the development of psychology
      as a health profession.

PMID- 8565927
TI  - Sustaining interventions in community systems: on the relationship between
      researchers and communities.
AB  - Important goals of research-based community interventions include the long-term
      maintenance of effects and fostering of collaboration between researchers and
      community leaders. This article reviews the challenges associated with
      transferring innovations to community systems, changing program delivery from an
      experimental context controlled by researchers to program delivery controlled by
      community organizations, and sustaining long-term effects of interventions. It is
      suggested that researchers who develop and implement community interventions in
      diverse health areas need to confront several issues: (a) fostering effective
      long-term relationships between researchers and the communities they study and in
      which they intervene and (b) designing and implementing interventions that are
      useful to community systems after the formal phase of research ends.

PMID- 8565928
TI  - Money matters: A meta-analytic review of the association between financial
      compensation and the experience and treatment of chronic pain.
AB  - Meta-analytic procedures were used to determine the relation between disability
      compensation and pain. Of the 157 relevant identified studies, only 32 contained
      quantifiable data from treatment and control groups. The majority of these
      exclusively examined chronic low back pain patients (72%). Overall, 136
      comparisons were obtained, on the basis of 3,802 pain patients and 3,849
      controls. Liberal procedures for estimating effect sizes (ESs) yielded an ES of
      .60 (p < .0002). Conservative procedures yielded an ES of .48 (p < .0005). Both
      ESs differed from zero, indicating that compensation is related to increased
      reports of pain and decreased treatment efficacy. These results are interpreted
      in light of current models of pain. Health policy implications are also
      discussed.

PMID- 8565929
TI  - Dieting behaviors and weight change history in female adolescents.
AB  - The prevalence of dieting, weight change history, and specific weight loss
      behaviors was examined in a population-based sample of 1,015 female 9th-12th
      graders. Healthy weight loss behaviors were reported much more frequently than
      unhealthy weight loss behaviors (e.g., healthy behaviors: exercise = 32.4%,
      decrease fat intake = 26.0%, reduce snacks = 25.0%, reduce kilocalorie intake =
      22.4%; unhealthy behaviors: fasting = 8.1%, diet pills = 5.4%, vomiting = 4.4%).
      Obesity status and restrained eating scores were positively related to greater
      history of weight loss episodes, pounds lost, and weight fluctuations and to
      greater use of healthy weight loss methods and weight loss programs. Implications
      for public health recommendations regarding dieting and its associated behaviors
      in female adolescents are discussed.

PMID- 8565930
TI  - Appraisal support predicts age-related differences in cardiovascular function in
      women.
AB  - The influence of appraisal support on age-related differences in cardiovascular
      function was examined. Resting assessments of heart rate, systolic blood pressure
      (SBP), diastolic blood pressure (DBP), respiratory sinus arrhythmia (RSA), and
      preejection period were obtained from 45 young and 20 elderly women. Consistent
      with prior research, results revealed that the elderly women had higher blood
      pressure and lower RSA than the young women. More important, appraisal support
      predicted age-related differences in SBP and DBP: Age predicted elevated blood
      pressure for women low in appraisal support, whereas age was unrelated to blood
      pressure for women high in appraisal support. These preliminary data suggest that
      appraisal support may be an important predictor of long-term physiological
      function and health.

PMID- 8565931
TI  - Personality and the incidence of hypertension among older men: longitudinal
      findings from the Normative Aging Study.
AB  - Personality predictors of hypertension incidence were studied in 838 community
      residing men from the Normative Aging Study. They were followed over a mean of 17
      years during which time 38% developed hypertension. Stepwise proportional hazards
      regression was used to identify scales from the Cattell 16 Personality Factor
      Questionnaire that predicted hypertension incidence, controlling for biomedical,
      social, and behavioral risk factors. There was a significant negative relation
      between the personality trait of emotional stability and the incidence of
      hypertension, controlling for baseline blood pressure, education, and alcohol
      consumption. These results support those who argue that personality
      characteristics predict the development of hypertension.

PMID- 8565932
TI  - Validation of measures of condom and other contraceptive use among women at high
      risk for HIV infection and unintended pregnancy.
AB  - This study assessed the applicability of the transtheoretical model of behavior
      change (J.O. Prochaska & C.C. DiClemente, 1983, 1984) to the measurement of
      contraceptive use among 296 women at high risk for HIV infection and
      transmission. Structural equation modeling suggested that a measure of general
      contraceptive use could be used to assess use of oral contraceptives and hormonal
      implants but that measurement of condom use required separate assessments for
      main and other partners. Self-efficacy (SE) and decisional balance scales were
      internally consistent for general contraceptive use, for condom use with main
      partners, and for condom use with other partners. Consistent with research on
      other health behaviors, SE scores rose significantly across stages, from
      precontemplation to maintenance, and a shift in decisional balance was observed
      for 2 of 3 behaviors. This measurement strategy may enhance the ability to
      evaluate prevention programs for women at risk.

PMID- 8565933
TI  - Genetics and disease in the horse.

PMID- 8565934
TI  - Changing concepts of COPD.

PMID- 8565935
TI  - The implications of biotechnology for equine practice.

PMID- 8565936
TI  - Transmembrane signalling: protein tyrosine phosphorylation and platelet
      activation.

PMID- 8565937
TI  - Equine pulmonary disease: a case control study of 300 referred cases. Part 1:
      Examination techniques, diagnostic criteria and diagnoses.
AB  - Three-hundred adult horses, referred from 1990 to 1993 inclusively, for pulmonary
      examination were assessed using standardised history taking and clinical,
      intrapleural pressure, arterial blood gases and pH, bronchoscopic and tracheal
      and broncho-alveolar lavage fluid (BALF) cytological examinations. Two-hundred
      and thirty-five cases were referred with overt signs of pulmonary disease and the
      remaining 65 cases were referred for pulmonary examination because of reduced
      exercise (usually racing) performance or prolonged dyspnoea after racing. No
      pulmonary disease was detected in 30 cases. The 270 horses with pulmonary disease
      included 148 cases (54.8%) of chronic obstructive pulmonary disease (COPD), 45
      (16.7%) of infectious or post infectious pulmonary disease, 7 (2.6%) of
      Streptococcus zooepidemicus pulmonary infection, 7 (2.6%) of lungworm infection,
      16 (5.9%) of primary exercise induced pulmonary haemorrhage (EIPH), 9 (3.3%) of
      chronic idiopathic hypoxaemia, 20 (7.4%) of miscellaneous identified pulmonary
      disorders and 18 (6.7%) of undifferentiated pulmonary disorders. Two cases of
      primary summer associated obstructive pulmonary disease (SPAOPD) were observed,
      but 9.5% of COPD affected horses additionally suffered from SPAOPD.

PMID- 8565938
TI  - Equine pulmonary disease: a case control study of 300 referred cases. Part 2:
      Details of animals and of historical and clinical findings.
AB  - Examination of historical and clinical details of 270 adult horses suffering from
      a variety of mainly chronic pulmonary diseases showed that the chronic
      obstructive pulmonary disease (COPD) group (median age 9 years) were the oldest,
      and that the COPD, chronic idiopathic hypoxaemia and exercise induced pulmonary
      haemorrhage (EIPH) groups had the longest duration of disease (median durations
      7, 12 and 9 months, respectively) with a median disease duration of 2 months for
      the remaining horses. A history of antecedent respiratory infection was present
      in 24.3% of all horses. Six out of 12 horses that grazed with donkeys suffered
      lungworm infection. Silage was fed to 11.3% of all horses, nonstraw beddings were
      utilised by 28.7% of horses and 8.7% of horses were maintained permanently
      outdoors. Environmental control had been unsuccessfully attempted in 47% of COPD
      cases prior to referral. Histories of poor athletic performance or of excessive
      post exercise dyspnoea were found to be less definitive indicators of pulmonary
      disease. Coughing was the most sensitive clinical indicator of pulmonary disease,
      being present in 71.1% of horses with pulmonary disorders. Nasal discharge was
      present in 50.4% of these horses and coughing or nasal discharge was present in
      86.7% of horses with respiratory disorders. Unilateral nasal discharge was
      inexplicably present in 3.3% of horses with pulmonary disease. Other clinical
      findings, including the presence of increased breathing effort, abnormal thoracic
      or tracheal auscultatory findings were less sensitive diagnostic parameters with
      pulmonary diseases, and were frequently absent unless severe pulmonary disease
      was present.

PMID- 8565939
TI  - Equine pulmonary disease: a case control study of 300 referred cases. Part 3:
      Ancillary diagnostic findings.
AB  - The majority of 270 adult horses with chronic pulmonary diseases had excessive
      volumes of respiratory secretions (RS) present in their trachea, elevated
      tracheal RS neutrophil ratios and lowered arterial oxygen partial pressures. Some
      control horses, had inexplicably elevated trachael RS neutrophil ratios. Only the
      chronic obstructive pulmonary disease (COPD) affected group had significantly
      elevated bronchoalveolar lavage fluid (BALF) neutrophil ratios. Maximal
      intrapleural pressure changes (max dPpl) were raised in 48% of COPD cases and
      rarely with other pulmonary disorders. Arterial pH or carbon doxide partial
      pressures values were seldom altered with any pulmonary diseases. Tracheal RS and
      BALF eosinophil ratios were raised with lungworm infection and idiopathic
      pulmonary eosinophilia.

PMID- 8565940
TI  - Equine pulmonary disease: a case control study of 300 referred cases. Part 4:
      Treatments and re-examination findings.
AB  - One-hundred and forty-seven of 270 (54.4%) horses suffering from pulmonary
      disorders were given at least one re-examination including, clinical,
      bronchoscopic, pulmonary function and cytological examinations after treatment
      and a further 83 of these horses (30.7%) had their clinical progress assessed by
      verbal or written reports. These examinations and progress reports showed high
      levels of partial or total recovery for most pulmonary disease categories,
      including chronic obstructive pulmonary disease, infectious, S. zooepidemicus and
      undifferentiated pulmonary disease and lungworm infection groups but not for the
      miscellaneous pulmonary disease (40% of these cases died), idiopathic chronic
      hypoxaemic or exercise induced pulmonary haemorrhage groups.

PMID- 8565941
TI  - Corneal stromal abscesses in the horse: a review of 24 cases.
AB  - The medical records of 24 horses with corneal stromal abscesses were reviewed.
      Twenty of the horses initially presented with a corneal ulcer, corneal opacity,
      or evidence of ocular pain. All of the horses were treated with topical
      antibiotics prior to referral. Most had also been treated with topical atropine
      sulphate and systemic flunixin meglumine. Ophthalmic examinations revealed focal,
      yellow-white corneal opacities, corneal vascularisation and evidence of
      iridocyclitis. Nine of the horses were treated primarily medically as the initial
      response to topical and systemic medication was rapid. Fifteen horses were
      treated both medically and surgically. Surgical treatment was undertaken when
      corneal rupture was imminent, the iridocyclitis was intractable or when there was
      minimal response to intensive medical therapy. The surgical procedure performed
      in most cases was a deep keratectomy with a conjunctival pedicle flap.
      Intraoperative specimens for cytology, culture, and/or histopathology contributed
      to the aetiological diagnosis in 5 of 8 cases in which preoperative cytology and
      cultures were nondiagnostic. All horses, excluding one that was enucleated at
      presentation for iris prolapse, had vision at discharge.

PMID- 8565942
TI  - Protein tyrosine phosphorylation in equine platelets: the effect of stimulation
      by thrombin and platelet-activating factor (PAF)
AB  - Protein tyrosine phosphorylation (PTP) in thrombin- and platelet-activating
      factor (PAF)-stimulated equine platelet activation was investigated in the
      absence and presence of 2 protein tyrosine kinase inhibitors (PTKIs), methyl 2,5
      dihydroxycinnamate (MDHC) and genistein. Washed equine platelets aggregated
      irreversibly in response to thrombin or PAF in an agonist concentration dependent
      fashion. MDHC produced an MDHC concentration and time dependent inhibitory effect
      on rate and extent of thrombin- and PAF-induced aggregations, whereas the effect
      of genistein on the same parameters was only genistein concentration dependent.
      Western blotting demonstrated tyrosine phosphorylated proteins in resting
      platelets. Changes in the PTP pattern occurred both when platelets were
      stimulated with varying concentrations of thrombin or PAF for a standard time (3
      min) or with a standard agonist concentration (0.17 u/ml thrombin or 10(-10)
      mol/l PAF) for varying times. Different patterns of PTP were produced by thrombin
      and PAF. 500 mumol/l MDHC and 300 mumol/l genistein each affected the PTP
      patterns produced in response to thrombin or PAF, but in different ways. PTP
      results with thrombin and PAF in the presence of 500 mumol/l MDHC were similar,
      as were those in the presence of 300 mumol/l genistein. However, there were many
      differences in the PTP results between thrombin (or PAF) in the presence of MDHC
      and between thrombin (or PAF) in the presence of genistein. Therefore, although
      both inhibitors are PTKIs, they have different effects on the PTP induced by
      either agonist. Our work has produced the first evidence of PTP in equine
      platelets. It is probable that the changes in PTP are related to events in the
      signal transduction pathway.

PMID- 8565943
TI  - Serial measurement of peripheral oestrogen and progesterone concentrations in
      oestrous mares to determine optimum mating time and diagnose ovulation.
AB  - Rapid enzyme-based immunoassays were used to measure concentrations of oestradiol
      17 beta and progesterone in daily blood samples recovered throughout oestrus and
      for a few days after ovulation from 34 Thoroughbred and 8 pony-type maiden,
      barren and foaling mares. The first detectable fall in oestradiol-17 beta levels
      occurred in 88% of the mares within the interval -72 to 0 h with respect to
      ovulation and in 65% of mares within the interval of -48 to 0 h. The results
      indicated that serial daily hormone assays of this type could, in a high
      proportion of animals, predict a correct time for a single mating and diagnose
      the occurrence of ovulation in Thoroughbred mares at stud in the absence of the
      present management system which includes repeated veterinary examinations of the
      ovaries. However, the absolute need for serial daily sampling from all mares to
      produce interpretable hormone profiles, and the cost of this sampling and the
      hormone assays, make the method impractical at the present time.

PMID- 8565944
TI  - Near infrared spectroscopy of pedal haemodynamics and oxygenation in normal and
      laminitic horses.
AB  - The present study applies near infrared spectroscopy (NIRS) to the haemodynamics
      of the pedal circulation in normal and laminitic horses. NIRS is a noninvasive
      technique which uses changes in light absorption at 4 wavelengths to provide
      information on the changes in cytochrome aa3 (cyt aa3) reduction-oxidation
      (redox) status, and changes in the tissue concentration of oxyhaemoglobin (O2Hb),
      deoxyhaemoglobin (HHb) and therefore total haemoglobin (tHb). Other studies have
      shown NIRS to be sensitive to changes in tissue oxygenation and perfusion in
      human cerebral and limb circulation. In this study, the NIRS sensor was applied
      to the dorsal surface of horses' hooves. Normal and laminitic animals (acute and
      chronic) were subjected to manoeuvres (cuff tourniquet; digital vessel occlusion
      at the palmar surface of the pastern; lifting of contralateral limb) predicted to
      change pedal haemodynamics. The procedures produced changes in pedal
      haemodynamics and oxygenation, which were similar to those observed in the
      ischaemic/reperfused human forearm. Laminitic differed from normal horses: return
      of HHb to baseline was slower and the change in cyt aa3 more rapid than normal in
      cases of chronic laminitis, taken to indicate reduced O2 stores as a result of
      compromised basal perfusion. In acute laminitis, baseline values did not
      fluctuate following any of the manoeuvres, suggesting haemostasis in the diseased
      hoof. NIRS is a useful noninvasive method to assess pedal vascular function in
      normal and laminitic horses.

PMID- 8565945
TI  - Frequency distribution of post race urine pH from standardbreds compared with
      thoroughbreds: research and regulatory significance.

PMID- 8565946
TI  - Combined oesophageal and tracheal duplication cyst in an Arabian filly.

PMID- 8565948
TI  - Equine anaesthesia: Horserace Betting Levy Board (HBLB) workshop. 31 October
      1995.

PMID- 8565947
TI  - Nitric oxide and equine laminitis: topical speculation or scientific fact?

PMID- 8565949
TI  - Nitric oxide donors as treatment for grass induced acute laminitis in ponies.
AB  - The potential for participation of the arginine-nitric oxide system in the
      aetiology of acute equine laminitis has been assessed. Nitric oxide (NO),
      produced by the action of NO synthase (NOS) on its substrate l-arginine, relaxes
      vascular smooth muscle to cause vasodilation. An attenuated normal vasodilatory
      tone may characterise the pathogenesis of acute equine laminitis. An intravenous
      infusion of 10% l-arginine in 0.9% saline caused vasodilatation in the hoof of a
      normal pony and immediate reperfusion of laminal tissues in an acutely laminitic
      pony, detected noninvasively by near infrared spectroscopy (NIRS), but the amino
      acid had little effect on systemic blood pressure. Treatment of acute laminitis
      with glyceryl trinitrate applied topically to the pasterns reduced the typical
      'bounding pulses' in treated limbs, reduced lameness and lowered systemic blood
      pressure. Nitric oxide is likely to participate in the multifactorial
      pathogenesis of equine laminitis.

PMID- 8565950
TI  - HBLB Workshop on Equine Anaesthesia: the importance of pharmacodynamics and
      pharmacokinetics.

PMID- 8565951
TI  - Determination of highest no effect dose (HNED) for local anaesthetic responses to
      procaine, cocaine, bupivacaine and benzocaine.
AB  - The highest no effect doses (HNEDs) for the local anaesthetic (LA) effects of
      procaine, cocaine, bupivacaine and benzocaine were determined using the heat
      lamp/hoof withdrawal model of Kamerling et al. (1985b) and the abaxial sesamoid
      block model of local anaesthesia. The heat lamp rapidly (4 or 5 s) increased the
      temperature of the superficial skin layers of the pastern to about 90 degrees C,
      at which point the animal sharply withdrew its hoof. Effective LA blockade
      precluded this response and superficial skin temperatures exceeded 120 degrees C.
      Thermal stimulus experiments were routinely terminated after 10 s of exposure to
      prevent undue tissue damage. Following abaxial sesamoid block with bupivacaine,
      the HNED for that drug was about 0.25 mg/site. Increasing the dose to 2 mg/site
      apparently produced complete and prolonged LA blockade. Analogous work showed
      that the HNED for procaine was about 2.5 mg/site. Similarly, the dose response
      curve for procaine was parallel with that of bupivacaine but was shifted 10-fold
      to the right. The duration of the LA response following procaine injection was
      less than for bupivacaine with the statistically significant response following
      40 mg/site injection lasting less than 45 min. Cocaine was less potent than
      procaine, showing a shallower dose response curve. The HNED for cocaine was less
      than 5 mg/site, although at this dose the duration of action was extremely short
      (< 7.5 min). Benzocaine had no significant LA action when a dose of 800 mg was
      applied topically as a 5% preparation. These results show that the HNEDs for
      bupivacaine and procaine are remarkably low, that cocaine is somewhat less potent
      as a LA than might be expected, and that 5% topical benzocaine has no significant
      pharmacology. The small doses of bupivacaine and procaine producing effective
      local anaesthesia suggests that developing plasma thresholds for these agents is
      likely to be very challenging.

PMID- 8565952
TI  - Basement membrane pathology: a feature of acute equine laminitis.
AB  - Thirty-two dorsal, mid-hoof wall, lamellar sections from 8 Standardbred horses,
      humanely killed 48 h after the administration of an alimentary carbohydrate
      overload, were sectioned and examined by light microscopy. Sections were stained
      with the connective tissue and basement membrane stains periodic acid-Schiff
      (PAS), Azan and periodic acid silver methanamine (PASM) and with routine
      haematoxylin and eosin (H&E). Lesions of the epidermal lamellae, attributable to
      laminitis, were graded in order of increasing severity from Grade N (normal),
      Grade 1 (mild), Grade 2 (moderate) to Grade 3 (severe and extensive). The grading
      system was based principally on changes to lamellar basement membrane (BM) which
      were clearly visible when the connective tissue stains PAS and PASM were used.
      Earliest changes were rounding of the basal cell nuclei and elongation of
      secondary epidermal lamellae (SELs). Secondary epidermal lamellae tips were
      pointed instead of round and the basement membrane had separated from the
      lamellae. In early Grade 1 lesions, this was obvious at the tips of the SELs
      where the BM had lifted to form teat-shaped bubbles. The absence of BM at the
      tips of secondary dermal lamellae, along with varying amounts of connective
      tissue, was considered a progression in severity and classified as Grade 2.
      Eventually, even the primary epidermal and primary dermal lamellae separated from
      each other and the empty shells of isolated BM, in what was once the tip of the
      primary epidermal lamella, signified that a global separation of the epidermal
      and dermal lamellae had occurred (Grade 3 lesion). The histopathological grading
      system correlated well with the degree of lameness at the time of euthanasia, (r2
      = 0.94) and apparently described the severity of laminitis accurately.
      Disintegration of the BM and failure of its attachment to the basal cells of the
      epidermis appears to be one of the earliest pathological events to occur in acute
      laminitis and could be the change that initiates the collapse of the lamellar
      architecture. Histopathological diagnoses of laminitis are strengthened when
      based on sections stained with at least PAS, in addition to routine H&E and
      should exhibit evidence of the BM pathology described here.

PMID- 8565953
TI  - Factors affecting motion characteristics of frozen-thawed stallion spermatozoa.
AB  - Five experiments were conducted to evaluate damage incurred in each processing
      step for cryopreservation of stallion spermatozoa. In Experiment 1, semen was
      centrifuged for 9 centrifugation times and the percentage of spermatozoa
      recovered after each treatment was calculated and spermatozoal motion
      characteristics analysed. Recovery of spermatozoa was > or = 80% when spermatozoa
      were centrifuged for > or = 10 min. Experiment 2 evaluated spermatozoa
      cryopreserved at 5 different concentrations in each of 2 extenders (skim milk-egg
      yolk-glycerol, SM-EYG; and lactose-EDTA, LAC). In SM-EYG, TMOT and PMOT were
      higher at spermatozoal concentrations of 20, 200 and 400 x 10(6)/ml (51%/41%,
      52%/44%, 50%/43%, respectively) than for samples frozen at > or = 800 x 10(6)
      spermatozoa/ml (41%/35%, 32%/27%; P < 0.05). Spermatozoa frozen in LAC at a
      concentration of 20 x 10(6)/ml resulted in the highest TMOT and PMOT (43% and
      30%, respectively, P < 0.05). The effect of freezing rate on motion
      characteristics of spermatozoa was evaluated in Experiment 3. The VCL of
      spermatozoa frozen in SM-EYG was the only parameter affected by freezing rate (P
      < 0.05). Experiment 4 evaluated motion characteristics after cryopreservation of
      spermatozoa in different sized straws (0.5 or 2.5 ml) in each of 2 extenders (SM
      EYG and LAC). In SM-EYG, PMOT (38%) and VCL (109 microns/s) were highest when
      spermatozoa were frozen in 0.5 ml straws (P < 0.05). In Experiment 5, spermatozoa
      thawed immediately after cryopreservation or thawed after storage in liquid
      nitrogen for 24-48 h were evaluated. There was no effect of length of storage in
      liquid nitrogen on spermatozoal motion characteristics (P < 0.05). Experiment 6
      evaluated the effects of cooling time to 5 degrees C (0, 2.5 and 5 h) on motion
      characteristics of spermatozoa cryopreserved in 2 extenders (SM-EYG and LAC).
      TMOT and PMOT were effected by cooling time, and there was a cooling-time-by
      extender interaction (P < 0.05). In SM-EYG, TMOT and PMOT were higher if
      spermatozoa were cooled to 5 degrees C prior to initiation of freezing than if
      freezing was initiated at 20 degrees C (P < 0.05). A suggested protocol for
      cryopreservation of stallion spermatozoa would include: 1) centrifugation at 400
      g for 14 to 16 min; 2) extension at 23 degrees C with SM-EYG to 400 x 10(6)
      spermatozoa/ml; 3) cool to 5 degrees C for 2.5 h; 4) package in 0.5 ml straws at
      5 degrees C; 5) freeze in liquid nitrogen vapour at -160 degrees C; and 6) thaw
      for 30 s in 37 degrees C water.

PMID- 8565954
TI  - Artificial insemination: assessing stallion semen quality after freezing.

PMID- 8565955
TI  - Ultrasonographic anatomy of the dorsal and abaxial aspects of the equine fetlock.
AB  - This paper describes normal ultrasound images of the soft tissues of the dorsal
      and abaxial aspects of the equine fetlock. The palmar aspect of the fetlock is
      not discussed because it is related to the suspensory apparatus and flexor tendon
      anatomy which has been previously described. Ultrasound scanning was performed
      with 7.5 MHz linear or 10 MHz sector probes and recorded on 7.5 cm U-matic
      videocassettes allowing further retrospective data analysis, computer
      manipulation and good image reproducibility. Sagittal, parasagittal, frontal and
      transverse ultrasound scans of 13 lameness free mature horses were compared to
      anatomically dissected leg specimens, anatomical sections and Magnetic Resonance
      Imaging scans of isolated limbs. The results are focused on the comparison
      between anatomical sections and ultrasonograms performed on the legs of nonlame
      horses. Ultrasonography was demonstrated to be a very accurate imaging procedure
      for soft tissue structures at the dorsal and abaxial aspects of the equine
      fetlock. Under clinical conditions, a thorough knowledge of normal
      ultrasonographic anatomy is critical for an accurate diagnosis of fetlock soft
      tissue injury.

PMID- 8565956
TI  - Limb movement adaptations in horses with experimentally induced fore- or hindlimb
      lameness.
AB  - The kinematic patterns of all limbs of 11 clinically nonlame Dutch Warmblood
      horses were studied during induced supporting limb lameness to gain insight into
      the compensation mechanisms horses use to manage lameness and to test kinematic
      limb variables for their significance as lameness indicators. Using the
      locomotion analysis system CODA-3, the kinematics of the horses were recorded
      while walking (1.6 m/s) and trotting (3.5 m/s) on a treadmill. A transient
      lameness model, evoking pressure on the hoof sole, was used to induce 3 degrees
      of fore- and hindlimb lameness. Joint angle patterns and hoof movements were
      analysed using joint angle/time diagrams and the hoof trajectories in the
      sagittal plane. Quantitative analysis of 13 selected variables in each limb was
      done using a 2-way analysis of variance. Hyperextension of the fetlock joint and
      flexion of the coffin joint during the stance phase decreased significantly (P <
      0.05) in the lame limb, both in fore- and hindlimb lameness, at both gaits. In
      the contralateral nonlame limbs both variables increased compensatorily. Flexion
      increased with increasing lameness in the proximal joints, i.e. the shoulder
      joint and even more the tarsal joint of the lame limb. The retraction of both
      forelimbs decreased during forelimb lameness at the walk, while in the lame
      hindlimb the protraction decreased. The hoof arcs were lower in the lame limb
      than in the nonlame limb, due to an increased hoof height in the nonlame limb
      during forelimb lameness and to a decreased height in the lame limb during
      hindlimb lameness. It was concluded that patterns of the distal joints reflect
      the different loadings of the limbs during lameness. Proximal joints acted as
      load dampers to reduce peak forces in the lame limb. Hyperextension of the
      fetlock and flexion of the coffin joint proved to be the most sensitive
      indicators for fore- and hindlimb lameness.

PMID- 8565957
TI  - Drug use and misuse: frontiers between biological science, bureaucracy and
      clinical pragmatism.

PMID- 8565958
TI  - Head and trunk movement adaptations in horses with experimentally induced fore-
      or hindlimb lameness.
AB  - The kinematic patterns of head and trunk were studied in horses during induced
      supporting limb lameness to understand the mechanisms horses use to compensate
      for lameness and to evaluate different symmetry indices for their significance as
      lameness indicators. Using the locomotion analysis system CODA-3 the kinematics
      of 11 clinically nonlame Dutch Warmblood horses were recorded while walking (1.6
      m/s) and trotting (3.5 m/s) on a treadmill. A transient lameness model, evoking
      pressure induced pain on the hoof sole, was used to induce 3 degrees of fore- and
      hindlimb lameness. Peak vertical displacement, velocity and acceleration of head,
      withers, tuber sacrale and both tuber coxae were quantified at different phases
      of the stride. Changes in these variables due to lameness and symmetry indices
      calculated as quotients of the values during the lame and nonlame stance phase
      were analysed using a 2-way analysis of variance. The head, withers and tuber
      sacrale showed a similar sinusoidal pattern in their vertical displacement,
      velocity and acceleration. During both fore- and hindlimb lameness at the trot,
      the vertical velocity of the trunk at impact of the lame limb decreased (P <
      0.05), during the lame stance phase the trunk was kept higher above the ground,
      maximal acceleration decreased and displacement amplitude was smaller than
      without lameness. Changes in movements of the head were much more expressed than
      movements of the withers during forelimb lameness and reversed during hindlimb
      lameness. At the walk, head movement patterns changed in the same way as at the
      trot, while withers and tuber sacrale patterns were hardly changed. Symmetry
      indices of all landmarks showed changes due to increasing lameness at the trot.
      The maximal vertical acceleration of the head and displacement amplitude of the
      tuber sacrale proved to be the best indicators to quantify a fore- and hindlimb
      lameness, respectively.

PMID- 8565959
TI  - Immunoperoxidase histochemistry as a diagnostic tool for detection of equine
      arteritis virus antigen in formalin fixed tissues.

PMID- 8565960
TI  - Transrectal ultrasonographic diagnosis of an ileocaecal intussusception in a
      horse.

PMID- 8565961
TI  - A possible case of Lyme borreliosis in a horse in the UK.

PMID- 8565962
TI  - Effects of anticonvulsant drug gabapentin on the enzymes in metabolic pathways of
      glutamate and GABA.
AB  - Gabapentin is a novel anticonvulsant drug. The anticonvulsant mechanism of
      gabapentin is not known. Based on the amino acid structure of gabapentin we
      explored its possible effects on glutamate and gamma-aminobutyric acid (GABA)
      metabolism in brain as they may relate to its anticonvulsant mechanisms of
      action. Gabapentin was tested for its effects on seven enzymes in the metabolic
      pathways of these two neurotransmitters: alanine aminotransferase (AL-T),
      aspartate aminotransferase (AS-T), GABA aminotransferase (GABA-T), branched-chain
      amino acid aminotransferase (BCAA-T), glutamine synthetase (Gln-S), glutaminase
      (GLNase), and glutamate dehydrogenase (GDH). In the presence of 10 mM gabapentin,
      only GABA-T, BCAA-T, and GDH activities were affected by this drug. Inhibition of
      GABA-T by gabapentin was weak (33%). The Ki values for inhibition of cytosolic
      and mitochondrial forms of GABA-T (17-20 mM) were much higher than the Km values
      for GABA (1.5-1.9 mM). It is, therefore, unlikely that inhibition of GABA-T by
      gabapentin is clinically relevant. As with leucine, gabapentin stimulated GDH
      activity. The GDH activity in rat brain synaptosomes was activated 6-fold and 3.4
      fold, respectively, at saturating concentrations (10 mM) of leucine and
      gabapentin. The half-maximal stimulation by gabapentin was observed at
      approximately 1.5 mM. Gabapentin is not a substrate of BCAA-T, but it exhibited a
      potent competitive inhibition of both cytosolic and mitochondrial forms of brain
      BCAA-T. Inhibition of BCAA-T by this drug was reversible. The Ki values (0.8-1.4
      mM) for inhibition of transamination by gabapentin were close to the apparent Km
      values for the branched-chain amino acids (BCAA) L-leucine, L-isoleucine, and L
      valine (0.6-1.2 mM), suggesting that gabapentin may significantly reduce
      synthesis of glutamate from BCAA in brain by acting on BCAA-T.

PMID- 8565963
TI  - Reduced function of gamma-aminobutyric acidA receptors in tottering mouse brain:
      role of cAMP-dependent protein kinase.
AB  - The single-locus mutant mouse tottering (tg) displays spontaneous seizures that
      resemble those in human petit-mal epilepsy. In order to examine alterations in
      GABAA receptor function which could arise as a result of this mutation, the
      influx of 36Cl- was determined using microsacs (membrane vesicles) isolated from
      the brain of tg/tg and coisogenic C57BL/6J (+/+) control mice. In microsacs from
      both tg/tg and +/+ strains, the maximum level of 36Cl- uptake induced by 50
      microM GABA was observed during five seconds of incubation at 28 degrees C.
      Compared to +/+, the GABA-dependent 36Cl- uptake in tg/tg microsacs was
      significantly lower and faded rapidly during longer incubations. The levels of
      gated 36Cl- uptake in tg/tg microsacs were 45 +/- 6.3%, 65 +/- 9.9%, and 33 +/-
      6.1% of control (+/+) values for 3-, 5-, and 10-s incubations, respectively.
      GABAA receptor-specific agonists (30 microM), muscimol, isoguvacine and THIP
      (4,5,6,7-tetrahydroisoazolo-[5,4-c]pyridin-3-ol) induced 36Cl- influx in the
      order muscimol > GABA > isoguvacine > THIP. This order was similar for both
      strains, but the agonist-dependent influx was always significantly lower in tg/tg
      compared to +/+. Treatment of the microsacs with 10 microM H-89, a membrane
      permeant inhibitor of the cAMP-dependent protein kinase (protein kinase A, PKA),
      was without effect on GABA-gated 36Cl- uptake in +/+, but increased the gated
      uptake in tg/tg microsacs by 44 +/- 16%. PKA was assayed using [gamma-32]ATP and
      kemptide as the substrate. Triton X-100 (0.1%) increased both the basal and 8-Br
      cAMP dependent PKA activity in microsacs by 3-4 four fold, showing that most of
      the enzyme was intravesicular. In the presence of Triton, the basal activity of
      PKA in the tg/tg preparations was twice that of +/+, while the strain difference
      was no longer apparent in assays containing 8-Br-cAMP. The data suggest that an
      abnormal elevation of protein kinase A activity in tottering mouse brain
      contributes to an impairment of GABAA receptor function. It is suggested that the
      resulting loss of inhibition could play a role in induction of the seizures which
      characterize the mutant phenotype.

PMID- 8565964
TI  - Epileptic discharges induced by pentylenetetrazol: ultrastructural alterations in
      identified neurons and glial cells (Helix pomatia).
AB  - The effects of sustained epileptic activity induced by pentylenetetrazol on
      morphology of buccal ganglia of Helix pomatia were investigated. Neuronal somata
      and processes as well as glial cells were evaluated after 5 hours of epileptic
      activity and after 5 hours under control conditions. After epileptic activity
      neurons showed signs of degeneration consisting of condensation of nuclear
      chromatin, decreased activity of Golgi apparatus, increased numbers of lamellar
      bodies and multivesicular bodies, clusters of vesicles and vacuoles, loss of
      microtubuli, and scattered lamellar bodies. Neuronal somata and large neuronal
      processes appeared less affected than the smaller processes. Glial cells showed
      signs of phagocytotic activity as increased cell size, numerous degenerating
      neuronal processes within the cytoplasm as well as lysosome like bodies and
      vacuoles. The changes developing along with epileptic activity were interpreted
      to indicate degeneration and subsequent phagocytotic activity of neuronal
      processes in synaptic regions of the ganglia. Thus, evidence is presented for
      synaptically induced degenerative processes in an intact nervous tissue that is
      not affected by seizure-induced alterations of respiration or systemic
      circulation.

PMID- 8565965
TI  - Antecedent tone presentation significantly delays rate of amygdala kindling.
AB  - External stimuli may contribute to seizure occurrence in at least two ways.
      First, the aberrant neuronal activity that precipitates a seizure could be
      elicited by certain external events; and second, external events could cue the
      organism to an impending seizure and result in a compensatory response that is,
      in effect, 'anti-convulsant'. While previous research has been aimed at
      addressing these issues, the results have been inconclusive. The present study
      was conducted to clarify and extend this prior work. Adult male Long-Evans hooded
      rats were chronically implanted with a kindling electrode and randomly assigned
      to one of two groups. The Tone group was presented with a 2-s auditory stimulus
      (Tone) beginning one second prior to and overlapping with the 1-s kindling
      stimulus. Animals in the No Tone group received only the kindling stimulus.
      Antecedent tone presentation significantly delayed the rate of amygdala kindling.
      The Tone group required significantly more stimulations to reach a Stage 5
      seizure than did the No Tone group. The possibility of this phenomenon providing
      a means to study the mechanisms underlying anti-epileptogenesis is discussed.

PMID- 8565966
TI  - Impairment of intracortical GABAergic inhibition in a rat model of absence
      epilepsy.
AB  - The WAG/Rij rat strain is characterized in its EEG by the manifestation of spike
      wave discharges which resemble in their spontaneous appearance and
      pharmacological sensitivity the absence epilepsy observed in humans. In order to
      test the hypothesis whether cellular intrinsic membrane and/or synaptic network
      properties in the neocortex are modified in this form of epilepsy, we analyzed
      with extra- and intracellular recording techniques the functional status of
      neocortical slices obtained from adult epileptic WAG/Rij rats and compared them
      with the data acquired from non-epileptic control Wistar rats. Intrinsic membrane
      properties, like resting membrane potential, neuronal input resistance and basic
      cellular firing characteristics, did not differ between these two strains.
      However, the analysis of extra- and intracellularly recorded synaptic responses
      revealed an intracortical hyperexcitability which was accompanied by a
      significant reduction in the efficiency of GABAergic inhibition. Our data
      indicate that the imbalance between intracortical excitatory and inhibitory
      mechanisms may at least contribute to the expression and augmentation of spike
      wave discharges in epileptic WAG/Rij rats.

PMID- 8565967
TI  - Regional induction of fos immunoreactivity in the brain by anticonvulsant
      stimulation of the vagus nerve.
AB  - Electrical stimulation of the vagus nerve exerts an antiepileptic effect on human
      partial-onset epilepsy, but little is known about the brain structures that
      mediate this phenomenon. Fos is a nuclear protein that is expressed under
      conditions of high neuronal activity. We utilized fos immunolabeling techniques
      on Sprague-Dawley rat brains to identify regions that are activated by
      antiepileptic stimulation of the left vagus nerve. Vagus nerve stimulation (VNS)
      induced specific nuclear fos immunolabeling in several forebrain structures,
      including the posterior cortical amygdaloid nucleus, cingulate and retrosplenial
      cortex, ventromedial and arcuate hypothalamic nuclei. In the brainstem, there was
      specific immunolabeling in vagus nerve nuclei, in the A5 and locus ceruleus
      noradrenergic nuclei, and in the cochlear nucleus. No labeling of these
      structures occurred in sham-operated, unstimulated control animals. Intense
      labeling also occurred in habenular nucleus of thalamus after vagus nerve
      stimulation, whereas only mild staining occurred in unstimulated animals. Several
      of the brain structures activated by VNS are important for genesis or regulation
      of seizures in the forebrain. These structures may mediate the antiepileptic
      effect of VNS.

PMID- 8565968
TI  - Stretch-shortening cycle during plantar flexion in young and elderly women and
      men.
AB  - The stretch-shortening cycle (SSC) is a combination of eccentric and concentric
      muscle actions. The purpose of the study was to compare the SSC of four different
      groups comprising a total of 29 women and 30 men, divided according to sex and
      age (i.e. 20-40 years and 70-85 years). A KIN-COM dynamometer was used for
      strength measurements of the plantar flexion of the right foot. An electromyogram
      (EMG) from the gastrocnemius muscle was recorded simultaneously. Maximal
      voluntary concentric muscle actions at 120 degrees.s-1 and 240 degrees.s-1 with
      and without prior eccentric muscle actions were performed. Average torque values
      of the range of motion between 90 degrees and 99 degrees of the ankle joint were
      extracted. All four groups were significantly stronger at 120 degrees.s-1 than at
      240 degrees.s-1 for pure concentric actions. The average torque values of the
      concentric phases in the SSC movement were significantly higher than the torque
      values for pure concentric actions in all four groups and at both velocities. The
      EMG was significantly lower or unchanged in the SSC movement compared to a pure
      concentric action in all groups. A larger percentage increase in torque with
      prior eccentric action was found in young women compared to young men at both
      velocities. Our results suggested that the enhanced performance was even more
      marked when a concentric action was preceded by an eccentric action in the young
      women than in the young men, probably due to better utilization of elastic
      forces, but we could not demonstrate any age-related differences in enhanced
      performance with SSC.

PMID- 8565969
TI  - Changes in Na+, K(+)-adenosinetriphosphatase, citrate synthase and K+ in sheep
      skeletal muscle during immobilization and remobilization.
AB  - The K+ balance and muscle activity seem to interact in a complex way with regard
      to regulating the muscle density of Na(+)-K+ pumps. The effect of immobilization
      was examined in ten sheep that had low muscle K+ content. Three additional sheep
      served as untreated controls. After being brought from pasture to sheep stalls
      one hindlimb was immobilized in a plaster splint for 9 weeks, and in five of the
      animals remobilization was carried out for a further 9 weeks. The weight bearing
      of the leg in plaster was recorded by a force plate. Open muscle biopsies from
      the vastus lateralis muscle were obtained before the study, after 9 weeks of
      immobilization, and after another 9 weeks of remobilization. The Na(+)-K+ pump
      density was measured as [3H]-ouabain binding to intact tissue, and citrate
      synthase activity was measured in tissue homogenate. The tissue content of K+ was
      measured in fat-free dried tissue. Muscle K+ content increased linearly by almost
      70% through the 18-week period independent of intervention. Immobilization
      reduced thigh circumference by 8% (P < 0.05). A slight decrease in the area of
      type I fibres at 9 weeks and a slight increase at 18-weeks was found. The [3H]
      ouabain binding was reduced by 39% and 22% in the immobilized and control legs,
      respectively, whereas citrate synthase activity was reduced by about 30% in both
      legs after 9 weeks of immobilization. During remobilization both the [3H]-ouabain
      binding and the citrate synthase activity increased to the same level as in the
      control animals. The plaster cast significantly reduced mass bearing of the
      immobilized leg, and a corresponding reduction in muscle activity must be assumed
      to have occurred in both legs as judged from citrate synthase activity. We
      concluded from this study that the reduction in the [3H]-ouabain binding during
      immobilization independent of an increase in muscle K+ content points to muscle
      activity as a strong stimulus for control of Na(+)-K+ pump density.

PMID- 8565970
TI  - Control of the rate of phosphocreatine resynthesis after exercise in trained and
      untrained human quadriceps muscles.
AB  - We examined the effect of differences in exercise intensity on the time constant
      (tc) of phosphocreatine (PCr) resynthesis after exercise and the relationships
      between tc and maximal oxygen uptake (VO2max) in endurance-trained runners (n =
      5) and untrained controls (n = 7) (average VO2max = 66.2 and 52.0 ml.min-1.kg-1,
      respectively). To measure the metabolism of the quadriceps muscle using
      phosphorus nuclear magnetic resonance spectroscopy, we developed a device which
      allowed knee extension exercise inside a magnet. All the subjects performed four
      types of exercise: light, moderate, severe and exhausting. The end-exercise PCr:
      [PCr+inorganic phosphate (P(i))] ratio decreased significantly with the increase
      in the exercise intensity (P < 0.01). Although there was little difference in the
      end-exercise pH, adenosine diphosphate concentration ([ADP]) and the lowest
      intracellular pH during recovery between light and moderate exercise, significant
      changes were found at the two higher intensities (P < 0.01). These changes for
      runners were smaller than those for the controls (P < 0.05). The tc remained
      constant after light and moderate exercise and then lengthened in proportion to
      the increase in intensity (P < 0.05). The runners had a lower tc at the same PCr
      and pH than the controls, particularly at the higher intensity (P < 0.05). There
      was a significant correlation between tc and [ADP] in light exercise and between
      tc and both end-exercise PCr and pH in severe and exhausting exercise (P < 0.05).
      The threshold of changes in pH and tc was a PCr: (PCr+P(i)) ratio of 0.5. There
      was a significant negative correlation between the VO2max and tc after all levels
      of exercise (P < 0.05). However, in the controls a significant correlation was
      found in only light and moderate exercise (P < 0.05). These findings suggest the
      validity of the use of tc at an end-exercise PCr: (PCr+P(i)) ratio of more than
      0.5 as a stable index of muscle oxidative capacity and the correlation between
      local and general aerobic capacity. Moreover, endurance-trained runners are
      characterized by the faster PCr resynthesis at the same PCr and intracellular pH.

PMID- 8565971
TI  - Heart rate and oxygen uptake relationship: a comparison of loaded marching and
      running in women.
AB  - Heart rate (beats.min-1; fc) measured during marching with a load is often used
      to predict the oxygen cost (l.min-1; VO2) of the activity. The prediction comes
      from the fc/VO2 relationship determined from laboratory measures of fc and VO2
      during treadmill running. Studies in men have suggested that this may not be
      appropriate although this has yet to be examined in women. This study, therefore,
      compared the fc/VO2 relationship between loaded marching and maximal running
      protocols in women. Sixteen female subjects [mean (SD), age 21.9 (2.3) years,
      height 6 (0.06) m, weight 62.6 (7.6) kg] had their fc (from three-lead chest
      electrodes) and VO2 measured first during standard treadmill run protocols, and
      again 1 week later during loaded marching protocols. The slopes and intercepts
      determined from linear regression of fc on VO2 for each individual for each
      protocol were compared as were the maximal fc(fcmax), VO2 and ratings of
      perceived exertion (RPE) from the last work period of each protocol in paired t
      tests. The fc/VO2 slopes (P < 0.01) and intercepts (P < 0.05) differed
      significantly between loaded marching and running. fcmax for loaded marching were
      90% of fcmax for running (P < 0.01) and VO2peak for loaded marching were 80% of
      those for running (P < 0.01). However, RPE at the final levels for the two
      protocols were not significantly different. The data suggest that in women the
      fc/VO2 relationships for loaded marching and for running are different. This
      difference is similar to that found in men when speed is held constant and the
      load and gradient are varied. The results suggest that it would be erroneous to
      use fc and VO2 measured during running protocols in the laboratory to estimate
      energy expenditure and work intensity during loaded marching in the field.

PMID- 8565972
TI  - A comparative analysis of physiological responses at submaximal workloads during
      different laboratory simulations of field cycling.
AB  - The purpose of this study was to evaluate the relationships between heart rate
      (fc), oxygen consumption (VO2), peak force and average force developed at the
      crank in response to submaximal exercise employing a racing bicycle which was
      attached to an ergometer (RE), ridden on a treadmill (TC) and ridden on a 400-m
      track (FC). Eight male trained competitive cyclists rode at three pre-determined
      work intensities set at a proportion of their maximal oxygen consumption
      (VO2max): (1) below lactate threshold [work load that produces a VO2 which is 10%
      less than the lactate threshold VO2 (sub-LT)], (2) lactate threshold VO2 (LT),
      and (3) above lactate threshold [workload that produces a VO2 which is 10%
      greater than lactate threshold VO2 (supra-LT)], and equated across exercise modes
      on the basis of fc. Voltage signals from the crank arm were recorded as FM
      signals for subsequent representation of peak and average force. Open circuit VO2
      measurements were done in the field by Douglas bag gas collection and in the
      laboratory by automated gas collection and analysis. fc was recorded with a
      telemeter (Polar Electro Sport Tester, PE3000). Significant differences (P <
      0.05) were observed: (1) in VO2 between FC and both laboratory conditions at sub
      LT intensity and LT intensities, (2) in peak force between FC and TC at sub-LT
      intensity, (3) in average force between FC and RE at sub-LT. No significant
      differences were demonstrated at supra-LT intensity for VO2. Similarly no
      significant differences were observed in peak and average force for either LT or
      supra-LT intensities. These data indicate that equating work intensities on the
      basis of fc measured in laboratory conditions would overestimate the VO2 which
      would be generated in the field and conversely, that using fc measured in the
      laboratory to establish field work intensity would underestimate mechanical
      workload experienced in the field.

PMID- 8565973
TI  - Thermal tolerance following artificially induced polycythaemia.
AB  - Polycythaemia has been shown to improve physical performance, possibly due to
      increased arterial oxygen transport. Enhanced thermoregulatory function may also
      accompany this manipulation, since a greater proportion of the cardiac output
      becomes available for heat dissipation. We further examined this possibility in
      five trained men, who participated in three-phase heat stress trials (20 min
      rest, 20 min cycling at 30% peak power (Wpeak) and 20 min at 45% Wpeak at 38.3
      (SEM 0.7) degrees C [relative humidity 41.4 (SEM 2.9)%]. Trials were performed
      during normocythaemia (control) and polycythaemia, obtained by reinfusion of
      autologous red blood cells and resulting in significant elevation of arterial
      oxygen transport. During the polycythaemic trials, the subjects demonstrated
      diminished thermal strain, as evidenced by a significant reduction in cardiac
      frequency (fc: 12 beats.min-1 lower throughout the test; P < 0.05), and reduced
      auditory canal temperatures (Tac) during the latter 20-min phase (P < 0.05).
      Forearm sweat onset was more rapid (363.0 compared to 1083.0 s; P < 0.05), and
      forearm sweat rate (msw) sensitivity was elevated from 1.80 to 2.91.mg.cm-2.min
      1.degrees C-1 (P < 0.05). Forehead msw was depressed during the final 20 min,
      while forearm msw was greater during all test phases, averaging 0.94 and 1.20
      mg.cm-2.min-1, respectively, over the 60 min. Skin blood flows for the upper
      back, upper arm and forearm were reduced (P < 0.05). Polycythaemia enhanced
      thermoregulation, through an elevation in forearm sweat sensitivity and msw, but
      not via increased cutaneous blood flow. These modifications occurred
      simultaneously with decreases in fc and Tac, resulting in greater thermal
      tolerance.

PMID- 8565974
TI  - Effects of exercise during normoxia and hypoxia on the growth hormone-insulin
      like growth factor I axis.
AB  - The response of plasma insulin-like growth factor I (IGF I) to exercise-induced
      increase of total human growth hormone concentration [hGHtot] and of its
      molecular species [hGH20kD] was investigated up to 48 h after an 1-h ergometer
      exercise at 60% of maximal capacity during normoxia (N) and hypoxia (H)
      (inspiratory partial pressure of oxygen = 92 mmHg (12.7 kPa); n = 8). Lactate and
      glucose concentrations were differently affected during both conditions showing
      higher levels under H. Despite similar maximal concentrations, the increase of
      human growth hormone (hGH) was faster during exercise during H than during
      N[hGHtot after 30 min: 8.6 (SD 11.4) ng.ml-1 (N); 16.2 (SD 11.6) ng.ml-1 (H); P <
      0.05]. The variations in plasma [hGH20kD] were closely correlated to those of
      [hGHtot], but its absolute concentration did not exceed 3% of the [hGHtot].
      Plasma IGF I concentration was significantly decreased 24 h after both
      experimental conditions [N from 319 (SD 71) ng.ml-1 to 228 (SD 72) ng.ml-1, P <
      0.05; H from 253 (SD 47) to 200 (SD 47) ng.ml-1, P < 0.01], and was still lower
      than basal levels 48 h after exercise during H [204 (SD 44) ng.ml-1, P < 0.01].
      Linear regression analysis yielded no significant correlation between increase in
      plasma [hGHtot] or [hGH20kD] during exercise and the plasma IGF I concentration
      after exercise. It was concluded that the exercise-associated elevated plasma
      [hGH] did not increase the hepatic IGF I production. From our study it would seem
      that the high energy demand during and after the long-lasting intensive exercise
      may have overridden an existing hGH stimulus on plasma IGH I, which was most
      obvious during hypoxia.

PMID- 8565975
TI  - Warm underwater water-jet massage improves recovery from intense physical
      exercise.
AB  - The effects of warm underwater water-jet massage on neuromuscular functioning,
      selected biochemical parameters (serum creatine kinase, lactic dehydrogenase,
      serum carbonic anhydrase, myoglobin, urine urea and creatinine) and muscle
      soreness were studied among 14 junior track and field athletes. Each subject
      spent, in a randomized order, two identical training weeks engaged in five
      strength/power training sessions lasting 3 days. The training weeks differed from
      each other only in respect of underwater water-jet massage treatments. These were
      used three times (20 min each) during the treatment week and not used during the
      control week. During the treatment week continuous jumping power decreased and
      ground contact time increased significantly less (P < 0.05) and serum myoglobin
      increased more than during the control week. It is suggested that underwater
      water-jet massage in connection with intense strength/power training increases
      the release of proteins from muscle tissue into the blood and enhances the
      maintenance of neuro-muscular performance capacity.

PMID- 8565976
TI  - Pre-exercise serum cortisol concentration and responses to laboratory exercise.
AB  - Relationships between the postexercise values of blood lactate concentration, pH,
      oxygen uptake, heart rate, power output on the one hand, and the pre- and
      postexercise blood cortisol concentrations on the other, were studied in 74 male
      and 40 female athletes (wrestlers and senior and junior rowers), performing
      graded exercise of increasing intensity. The senior rowers, junior rowers and
      wrestlers had different exercise protocols. The senior rowers of both sexes had
      significantly higher rest concentrations of serum cortisol than the junior
      athletes. A significant correlation between postexercise lactate concentrations
      and pre-exercise cortisol concentrations was found in all the male groups
      ("common" r = 0.515, P < 0.001), but not in the female ones (r = 0.162). It was
      concluded that the pre-exercise cortisol concentrations might condition anaerobic
      glycolytic metabolism in physical exercise.

PMID- 8565977
TI  - Physical work load, physical capacity and strain among elderly female aides in
      home-care service.
AB  - A study was undertaken to investigate physical work load, physical capacity,
      physical strain and perceived health among elderly aides in home-care service. A
      secondary aim was to compare the work load and strain between the two main types
      of home-care service available in Sweden today. Work tasks and their distribution
      among 20 elderly aides (aged 45-65 years), working in open home-care service
      (clients living in their original flats or houses) and at service apartment
      houses (clients living in private flats constructed for the elderly and
      handicapped with service functions) were observed during whole work days. Heart
      rate and number of steps taken were also measured continuously during the whole
      work day. Oxygen consumption and work postures for upper arm and back were
      measured during parts of the work day. The results showed that home-care work is
      characterised by long periods of standing and walking and that postures
      potentially harmful for the low back and shoulders occurred frequently. Average
      physiological strain measured as relative oxygen consumption and heart rate
      during the work day did not exceed present recommendations. Average physical work
      load and strain in open home-care service slightly exceeded those in service
      apartment houses because of more frequent cleaning and walking outdoors. Many
      aides in this study showed slightly reduced physical capacity, and
      musculoskeletal problems were common. Many elderly aides in home-care service are
      probably exposed at work to high risks of overexertion and impaired health as a
      result of high postural loads in combination with other known important factors,
      such as time stress and lack of equipment.

PMID- 8565978
TI  - In vivo Achilles tendon loading during jumping in humans.
AB  - Elastic behaviour of the human tendomuscular system during jumping was
      investigated by determination of the in vivo Achilles tendon force. A buckle-type
      transducer was implanted under local anaesthesia around the right Achilles tendon
      of an adult subject. After calibration, the Achilles tendon force was recorded
      together with the triceps surae muscle electromyogram activity and high speed
      filming and ground reaction force during: a maximal vertical jump from a squat
      position, a maximal vertical jump from an erect standing position with a
      preliminary counter-movement, and repetitive submaximal hopping on the spot.
      Jumping heights were 33, 40 and 7 cm in the squat, the counter movement and the
      hopping positions, respectively. The peak Achilles tendon force and mechanical
      work by the calf muscles were 2233 N and 34 J in the squat jump, 1895 N and 27 J
      in the counter movement jump, and 3786 N and 51 J when hopping. The changes in
      tendon length were estimated assuming a stiffness constant calculated from the
      tendon architecture. The percentages of elastic energy stored in the Achilles
      tendon during jumping were 23%, 17% and 34% of the total calf muscle work in the
      squat jump, the counter movement jump, and hopping, respectively.

PMID- 8565979
TI  - Influence of central command and ergoreceptors on the splanchnic circulation
      during isometric exercise.
AB  - The splanchnic circulation can make a major contribution to blood flow changes.
      However, the role of the splanchnic circulation in the reflex adjustments to the
      blood pressure increased during isometric exercise is not well documented. The
      central command and the muscle chemoreflex are the two major mechanisms involved
      in the blood pressure response to isometric exercise. This study aimed to examine
      the behaviour of the superior mesenteric artery during isometric handgrip (IHG)
      at 30% maximal voluntary contraction (MVC). The pulsatility index (PI) of the
      blood velocity waveform of the superior mesenteric artery was taken as the study
      parameter. A total of ten healthy subjects [mean age, 21.1 (SEM 0.3) years]
      performed an IHG at 30% MVC for 90 s. At 5 s prior to the end of the exercise,
      muscle circulation was arrested for 90 s to study the effect of the muscle
      chemoreflex (post exercise arterial occlusion, PEAO). The IHG at 30% MVC caused a
      decrease in superior mesenteric artery PI, from 4.84 (SEM 1.57) at control level
      to 3.90 (SEM 1.07) (P = 0.015). The PI further decreased to 3.17 (SEM 0.70) (P =
      0.01) during PEAO. Our results indicated that ergoreceptors may be involved in
      the superior mesenteric artery vasodilatation during isometric exercise.

PMID- 8565980
TI  - Role of agonist and antagonist muscle strength in performance of rapid movements.
AB  - Six subjects performed rapid self-terminated elbow movements under different
      mechanical conditions prior to, and 5 weeks after an elbow extensor strengthening
      programme. Despite the large difference in the strengths of elbow flexors and
      extensors, the pretest did not demonstrate significant differences between the
      movement time of flexion and extension movements performed under the same
      mechanical conditions. The results obtained in the posttest demonstrated a
      decrease in movement time (i.e. an increase in movement speed) in both elbow
      flexion and extension movements under some mechanical conditions. In addition,
      flexion movements demonstrated a relative increase in the acceleration time
      (acceleration time as a proportion of the movement time). It was concluded that
      the strength of both the agonist and antagonist muscles was important for the
      performance of rapid movements. Stronger agonists could increase the acceleration
      of the limb being moved, while stronger antagonists could facilitate the arrest
      of the limb movement in a shorter time, providing a longer time for acceleration.

PMID- 8565981
TI  - Effects of altitude on top speeds during 1 h unaccompanied cycling.
AB  - The present world record for 1 h unaccompanied cycling (55.291 km) was set by T.
      Rominger in November 1994 at sea level (Bordeaux, France). However, maximal
      aerobic cycling performances can be expected to increase at altitude because, for
      a given air temperature, air density decreases more than VO2max. The combined
      effect of these opposite trends results in an improvement of performances. In
      this study, based on the aerodynamics of track cycling, and assuming an average
      decrease of VO2max with altitude as from the literature, we show that the ideal
      altitude for Rominger is 4000 m where he could cover 60.1 km in 1 h. To our
      knowledge, only two cyclists attempted at close time intervals to set the 1 h
      record at sea level and at altitude (Mexico, 2230 m above sea level): F. Moser
      and J. Longo. Their increase of performance with altitude was only about 50% of
      that predicted on the basis of similar calculations as performed on Rominger.
      This suggests that the decrease of VO2max resulting from altitude is greater for
      athletes than for average trained subjects and/or that the fraction of VO2max
      that can be maintained throughout 1 h decreases with altitude.

PMID- 8565982
TI  - Capillary density measurements in skeletal muscle using immunohistochemical
      staining with anti-collagen type IV antibodies.
AB  - An immunohistochemical method, based on an indirect peroxidase method for
      staining of capillaries containing collagen type IV, is presented. Biopsies from
      the vastus lateralis muscle of eight endurance trained runners were stained and
      counted for capillaries with the collagen type IV method and with the widely used
      amylase-PAS method. The mean number +/- SEM of capillaries per fibre was 2.48 +/-
      0.09 with the collagen type IV method and 2.41 +/- 0.09 with the collagen type IV
      method and 2.41 +/- 0.08 with the amylase method. The 95% confidence intervals
      for the differences between the two methods were - 0.03 to 0.15. We conclude that
      the collagen type IV immunohistochemical method for capillary staining is
      comparable with the amylase method under optimum conditions, but that it is
      likely to be more dependable. It also has the advantage that it reveals fibre
      outlines.

PMID- 8565983
TI  - Multicentre comparative study of the efficacy and safety of azithromycin compared
      with amoxicillin/clavulanic acid in the treatment of paediatric patients with
      otitis media.
AB  - An open multicentre study was conducted in 484 children between the ages of 6
      months and 12 years with otitis media to compare the efficacy, the safety and the
      tolerance of once-daily azithromycin given for three days versus thrice-daily
      amoxicillin/clavulanic acid (CA) given for ten days. A satisfactory response
      (cure plus improvement) was noted 10 to 14 days after the start of treatment in
      199 of 215 (92.6%) azithromycin-treated children and in 186 of 198 (93.9%)
      amoxicillin/CA-treated children. The relationship between treatment and clinical
      response was independent of chronicity of infection and the presence or absence
      of a perforated eardrum. Improvement in signs and symptoms of otitis media
      occurred significantly more rapidly in the children treated with azithromycin.
      Treatment-related or possibly treatment-related adverse events were recorded in
      11 of 243 (4.5%) azithromycin-treated patients and in 20 of 240 (8.3%) treated
      with amoxicillin/CA. No patients in the azithromycin treatment group were
      withdrawn from treatment, but six amoxicillin/CA patients, including two < 2
      years of age, discontinued treatment prematurely because of adverse events; the
      difference between treatment groups was statistically significant (p = 0.0146).
      It is concluded that azithromycin given as an oral suspension once daily for
      three days is as safe and effective as amoxicillin/CA given thrice daily for ten
      days in the treatment of children with otitis media.

PMID- 8565985
TI  - Low prevalence of diphtheria antitoxin in children and adults in northern
      Germany.
AB  - Recent outbreaks of diphtheria in neighbouring eastern European countries and in
      the Russian Federation prompted us to evaluate immunity to diphtheria in a sample
      of 400 healthy individuals (210 male, 190 female) from northern Germany. An age
      stratified study population was chosen, including newborns, children, adults and
      elderly persons over 60 years divided into 8 subgroups of 50 persons each.
      Diphtheria antitoxin was tested by enzyme immunoassay. The median antitoxin titre
      was 0.39 IU/ml. There was no difference in the median antitoxin titres of men and
      women. Inadequate immunity to diphtheria was detected in more than 90% of the 400
      individuals tested, including 4% who completely lacked immunity (titre < 0.01
      IU/ml), a further 20% with minimal protection (titre 0.01-0.1 IU/ml) and the
      majority of 69% who showed relative protection for less than one year (titre 0.1
      1.0 IU/ml). Only 7% exhibited lasting protection for more than five years (titre
      > 1.1). Newborns and persons over 50 years of age constituted the least protected
      groups, with significantly lower median antitoxoid titres than the other age
      groups (p < 0.001). The absence of protective immunity in 7 of the 50 newborns
      examined (14%) reflects the inadequate protection of women of reproductive age.
      Children aged 1 to 10 years were the best immunized and protected group. The
      results suggest that routine booster immunizations of the majority of the adult
      population would be advisable in view of the ongoing migration from and the
      visits to high-risk areas.

PMID- 8565984
TI  - Intestinal and extraintestinal cryptosporidiosis in AIDS patients.
AB  - In a prospective study in AIDS patients with chronic diarrhea, the overall
      prevalence of intestinal cryptosporidiosis was 15.6% (43/275). The prevalence was
      higher in homosexual patients (33.3%) than in intravenous drug abusers (10.6%) (p
      < 0.001). Extraintestinal infection was present in 30% (13/43) of the patients
      with known intestinal cryptosporidiosis. Eight of the 13 (61.5%) patients with
      extraintestinal cryptosporidiosis had Cryptosporidium in the bile and 7 of 13
      (16.28%) had it in the sputum. Of the seven patients with Cryptosporidium in the
      sputum, four had respiratory symptoms and an abnormal chest radiograph, although
      another pulmonary pathogen was isolated simultaneously. Two other patients from
      whom Cryptosporidium was the sole respiratory pathogen isolated had no
      respiratory symptoms and normal chest radiographs. The seventh patient had
      pulmonary symptoms, interstitial infiltrate on chest radiograph and excessive
      activity on a pulmonary Gallium scan; Cryptosporidium was the only organism
      detected in induced sputum and bronchoalveolar lavage specimens. The mean CD4+
      lymphocyte count in patients with extraintestinal cryptosporidiosis was 55
      cells/mm3.

PMID- 8565986
TI  - Prevalence of infection by human T-cell leukemia virus types I and II in southern
      Spain.
AB  - To assess the spread of human T-cell leukemia virus (HTLV) type I and II in
      different population groups at potential risk of infection in Spain, a total of
      756 subjects were studied: 453 belonging to groups at risk for retrovirus
      infection, 255 with diseases potentially linked to HTLV-I/II infection and 48
      immigrants from endemic areas. An HTLV-I viral-lysate enzyme immunoassay (EIA)
      with a recombinant transmembrane envelope protein incorporated was used to screen
      serum samples. Reactive specimens were confirmed by Western blot strips spiked
      with recombinant proteins that differentiated HTLV-I from HTLV-II. Infection was
      then verified by the polymerase chain reaction (PCR). Serum samples from 19 of
      the 756 subjects analyzed (2.5%) were reactive for HTLV by EIA. One of these was
      from an intravenous drug user (IVDU) in whom HTLV-II infection was confirmed by
      Western blot and PCR; a specimen from another IVDU showed Western blot reactivity
      for both retroviruses, but PCR results were negative. Lastly, Western blot
      confirmed the presence of HTLV in one of the immigrant subjects. Western blot did
      not verify HTLV infection in the remaining 16 cases, indicating a high rate of
      nonspecific anti-HTLV reactivity when a second-generation EIA screening test was
      applied. These results suggest that HTLV is present in Spain among populations at
      high risk for HTLV, although at a very low rate and restricted to intravenous
      drug users and individuals immigrating from endemic areas.

PMID- 8565987
TI  - Seroprevalence of rubella among women of childbearing age in Switzerland.
AB  - A seroepidemiological study was carried out in Switzerland to define the
      population susceptible to rubella among women of childbearing age. IgG antibodies
      to rubella virus were determined in 9,046 women giving birth between 1 August
      1990 and 30 September 1991 in 23 of 26 Swiss cantons. These sera represented 10
      20% of the yearly total number of births in each Swiss canton. Anti-rubella IgG
      was measured by an automated enzyme-linked fluorescent assay for use with a
      commercial system (Vidas Rub IgG, bio-Merieux, France). Before the study
      population was screened, the commercial system was compared to the traditional
      hemagglutination-inhibition (HAI) test using 500 consecutive samples from
      parturient women. The sensitivity was 97.7%, the specificity was 100%, and
      agreement between the two tests was 97.8%. The discrepancies corresponded to very
      low titres of antibodies as measured by HAI. The seroprevalence of rubella
      nationwide in women of childbearing age in Switzerland was 94.3%. The
      seroprevalence was higher (96.5%) in the 5,677 women of Swiss nationality than in
      the 3,090 women of a different nationality (90.4%) (p < 0.001). In Swiss women
      the seroprevalence of rubella did not increase significantly with age and was
      identical in primiparous and in multiparous women, thus indicating that women of
      childbearing age are probably not sufficiently immunised.

PMID- 8565988
TI  - Successful treatment of catheter-related fusarial infection in immunocompromised
      children.
AB  - Fusarium infection is increasingly reported in immunocompromised patients. The
      role of central venous catheters as potential portals of entry for Fusarium is
      possibly underestimated. Four cases of catheter-related fusarial infection in
      children with acute leukemia or a solid tumor are described. These patients had
      an excellent response to removal of the central venous catheter and treatment
      with amphotericin B.

PMID- 8565989
TI  - Antifungal combination therapy with granulocyte colony-stimulating factor and
      fluconazole in experimental disseminated candidiasis.
AB  - The present studies were performed to determine whether any beneficial
      interaction results from combination therapy with recombinant human granulocyte
      colony-stimulating factor (GCSF) and fluconazole in disseminated candidiasis in
      mice. Fluconazole extended survival and reduced tissue counts. GCSF had no direct
      benefit, but GCSF combined with fluconazole extended survival beyond that for
      fluconazole alone and reduced renal tissue counts below those for fluconazole
      alone. Thus, GCSF and fluconazole may be a useful combined therapy for
      disseminated candidiasis.

PMID- 8565990
TI  - In vivo acquisition of extended-spectrum beta-lactamase in Salmonella enteritidis
      during antimicrobial therapy.
AB  - The recovery of a Salmonella enteritidis strain that acquired resistance to beta
      lactams (including cefotaxime), to aminoglycosides and to chloramphenicol
      subsequent to cefotaxime therapy is reported. This resistance pattern to beta
      lactams was due to the presence of an extended-spectrum beta-lactamase. The
      isoelectric point of this extended-spectrum beta-lactamase was 6.3. The
      resistance genes were located on a transferable high-molecular-weight plasmid.

PMID- 8565991
TI  - Gastrointestinal adenovirus infections in a tertiary referral centre in Saudi
      Arabia.
AB  - To determine the prevalence of adenovirus and its serotypes in diarrhoeal stools
      in Saudi Arabia, 3,000 stool specimens were collected prospectively from subjects
      of all ages over a 28-month period. A total of 220 positive isolates were
      obtained. Fifteen serotypes were found, serotypes 40 and 41 being the most
      prevalent. Underlying disorders were found in the majority of patients, leukaemia
      being the most common single underlying condition. This investigation represents
      the first detailed study of the epidemiology of gastrointestinal adenovirus
      infections in Saudi Arabia.

PMID- 8565992
TI  - Testing of saliva and serum for HIV in high-risk populations. Ad Hoc Group for
      the Comparative Saliva and Serum Study.
AB  - Paired samples of saliva and serum from 286 high-risk subjects were tested for
      HIV using two commercial enzyme immunoassays following the same WHO testing
      strategy supplemented with a Western blot technique. Agreement between HIV
      testing in both sample types was 98.9% (95% confidence interval: 97.7-100). The
      sensitivity of an EIA (Wellcozyme GACELISA) alone for saliva was 100% (133/133)
      and the specificity 98.7% (151/153). These results support previous data showing
      that in some situations saliva might be an effective alternative to serum for HIV
      testing.

PMID- 8565993
TI  - Use of a new oligonucleotide probe for detection of colonization factor antigen
      III gene in enterotoxigenic Escherichia coli.
AB  - An alkaline phosphatase-labeled 30-mer oligonucleotide probe was designed to
      detect the gene for pilus colonization factor antigen III (CFA/III) of the human
      type of enterotoxigenic Escherichia coli (ETEC). The CFA/III probe was used to
      identify CFA/III-producing ETEC among 303 Escherichia coli obtained from subjects
      with traveler's diarrhea. Six isolates positive for the CFA/III gene were found.
      This result was confirmed immunologically by using a specific monoclonal antibody
      developed against CFA/III. These six isolates, isolated from travelers returning
      from India, Pakistan and China, were all positive for the gene of heat-labile
      enterotoxin and possessed an identical serotype (025:H-).

PMID- 8565994
TI  - Rapid polymerase chain reaction method for specific detection of toxigenic
      Clostridium difficile.
AB  - A rapid polymerase chain reaction (PCR) method for detection of toxigenic
      Clostridium difficile directly from fecal samples by amplification of toxin A
      gene fragments was investigated. The technique was applied to monitor the spread
      of the microorganism in a long-term care ward with a relatively high incidence of
      overt episodes of diarrhea. The PCR approach has several advantages over
      traditional methods, rapidly allowing the specific detection of toxigenic
      Clostridium difficile strains from stool samples in both symptomatic and
      asymptomatic subjects with toxigenic strains. This PCR method allows early
      detection of toxigenic Clostridium difficile and could thus represent a powerful
      tool for the surveillance of epidemics.

PMID- 8565995
TI  - Evaluation of a commercial polymerase chain reaction assay for Chlamydia
      trachomatis and suggestions for improving sensitivity.
AB  - A commercial polymerase chain reaction (PCR) assay (Amplicor, Roche) for
      Chlamydia trachomatis was compared with a direct fluorescent antibody (DFA) test
      using urethral and cervical samples, many of which on the basis of prior testing
      by DFA contained small rather than large numbers of elementary bodies. Urine
      samples were collected from patients in a sequential unselected manner. Of 244
      clinical specimens (138 male urethral and cervical; 106 male and female urine),
      66 were positive by both DFA and PCR and 141 were negative by both tests. Nine
      samples were DFA negative and PCR positive, and 28 samples were DFA positive and
      PCR negative. However, 24 (86%) of the latter samples contained fewer than ten
      elementary bodies. When serial dilutions of laboratory stock strains (serovars E
      and H) were tested, the DFA test detected Chlamydia trachomatis at a dilution
      tenfold greater than the PCR. Furthermore, of five DFA-positive clinical samples,
      three that were PCR negative when tested according to the manufacturer's
      instructions were positive when they were diluted less. A modification of the PCR
      assay along these lines might improve sensitivity.

PMID- 8565996
TI  - Criteria for testing the susceptibility of Streptococcus pneumoniae to cefotaxime
      and its desacetyl metabolite using 1 microgram or 30 micrograms cefotaxime disks.
AB  - In vitro susceptibility tests were performed with 350 selected strains of
      Streptococcus pneumoniae to evaluate disk diffusion tests with 30 micrograms and
      1 microgram cefotaxime disks. Zones were compared to MICs of cefotaxime with and
      without its desacetyl metabolite. Cefotaxime was two to eight times more active
      than desacetyl cefotaxime, but the two compounds were additive when combined in
      vitro. For 30 micrograms disks, zone size breakpoints were < or = 27 mm, 28-30 mm
      and > or = 31 mm for resistant, intermediate and susceptible, respectively. For 1
      microgram disks, those zone size criteria were reduced to < or = 13 mm, 14-16 mm
      and > or = 17 mm. The 30 micrograms disk that is currently available for testing
      other species can be used for testing pneumococci; however, the 1 microgram disk
      has some important advantages.

PMID- 8565997
TI  - Isolation of Helicobacter pylori in a six-day-old newborn.

PMID- 8565998
TI  - Stenotrophomonas maltophilia in cystic fibrosis patients.

PMID- 8565999
TI  - Report of catheter-associated Trichosporon pullulans break-through fungemia in a
      cancer patient.

PMID- 8566000
TI  - Emergence of different resistance mechanisms in Pseudomonas aeruginosa in a
      patient treated with imipenem.

PMID- 8566001
TI  - Inactivation of diaminopyrimidines and sulfonamides in Barbour-Stoenner-Kelly
      medium for isolation of Borrelia burgdorferi.

PMID- 8566002
TI  - Epitopes for human CD4+ cells on diphtheria toxin: structural features of
      sequence segments forming epitopes recognized by most subjects.
AB  - The sequence regions of diphtheria toxin (DTX) recognized by CD4+ T cells of
      seven healthy humans of different major histocompatibility complex haplotypes
      were identified. Overlapping synthetic peptides, screening the DTX sequence, were
      used to test in proliferation assays unselected blood CD4+ cells, or DTX-specific
      CD4+ lines propagated by stimulation with DTX of blood mononuclear cells. Blood
      CD4+ cells and DTX-specific CD4+ lines gave consistent results. Although each
      subject had an individual pattern of peptide recognition, six peptide sequences
      (residues 271-290, 321-340, 331-350, 351-370, 411-430 and 431-450) were
      recognized by all subjects. In the native DTX molecule, these sequence regions
      are flanked by sequence loops exposed on the DTX surface. They overlap uncharged
      segments of the DTX sequence. These structural properties may be general
      requirements for immunodominance in CD4+ cell sensitization in humans.

PMID- 8566003
TI  - Raf-1 provides a dominant but not exclusive signal for the induction of CD69
      expression on T cells.
AB  - Stimulation of the T cell antigen receptor (TCR) induces a number of
      intracellular signaling pathways which lead to the transcription of a variety of
      new genes. Of the newly synthesized proteins, the earliest to be detected on the
      cell surface is the type II integral membrane protein CD69. Cross-linking of this
      activation antigen induces signaling events related to T cell activation. The
      proto-oncogene product Ras has been reported to up-regulate CD69. However, which
      of the potential effectors of Ras induces the expression of CD69 has remained
      unclear. Using transient transfection, we have shown a constitutively active form
      of the serine/threonine kinase Raf-1 to be sufficient to induce CD69 expression
      in human Jurkat T cells. Raf-1 was further shown to be necessary for PMA-induced
      CD69 expression, since transfection of a dominant inhibitory form of Raf-1
      blocked the up-regulation of CD69 by PMA. In addition, studies with the calcium
      ionophore ionomycin identified a previously uncharacterized pathway regulating
      the expression of CD69 in T cells. Elevation of intracellular calcium induced the
      expression of CD69 in both Jurkat cells and peripheral blood T cells. This effect
      was sensitive to the immunosuppressive drug cyclosporin A, indicating that
      calcium-induced CD69 expression is mediated by the protein phosphatase
      calcineurin. Taken together, these results define Raf-1 as the major signaling
      mediator of CD69 expression in T cells and suggest that multiple mechanisms exist
      to regulate the level of CD69 expression following TCR stimulation.

PMID- 8566004
TI  - A sensitive assay for detecting low-affinity interactions at the cell surface
      reveals no additional ligands for the adhesion pair rat CD2 and CD48.
AB  - The ligand for the T cell antigen CD2 is CD48 in rodents, but CD58 in humans. The
      extracellular parts of these three antigens are structurally related in that all
      contain two immunoglobulin superfamily (IgSF) domains. There have been reports of
      alternative ligands for CD2 in the human, but not so far in rodents. We describe
      the analysis of ligands for rat CD2 and CD48 using fluorescent beads capable of
      displaying a high ligand density and detecting low-affinity interactions like
      that of CD2 with CD48 (Kd = 60-90 microM). Monovalent chimeric proteins
      containing the two IgSF domains of rat CD48 or CD2 and domains 3 and 4 of rat CD4
      (CD4d3+4) were anchored to fluorescent covaspheres via a CD4 monoclonal antibody
      (mAb) with the CD48 or CD2 domains available for ligand binding. Multivalent CD48
      CD4d3+4 covaspheres gave strong specific binding to rat CD2 expressed on the
      surface of transfected Jurkat cells. CD48-CD4d3+4 was compared with CD48-IgG and
      CD48-IgM as tools for detecting binding at the cell surface. Soluble divalent
      CD48-IgG and decavalent CD48-IgM bound to soluble CD2 with a Koff of around 10(
      3) s-1 as determined using a BIAcore biosensor. However, binding to cells by CD48
      IgG and CD48-IgM was only detectable when they were immobilized on covaspheres
      and represented no increase in sensitivity over CD48-CD4 covaspheres when tested
      for binding to cells expressing high and low levels of CD2. CD48-CD4d3+4
      covaspheres only bound to rat cells expressing CD2. In the reverse orientation,
      bindign of CD2-CD4d3+4 covaspheres was dependent on expression of CD48. Pre
      incubation of cells with CD2 or CD48 mAb abolished all binding of CD48-CD4d3+4 or
      CD2-CD4d3+4, respectively. The data provide no evidence for an alternative ligand
      for rat CD2 or CD48.

PMID- 8566005
TI  - Lack of inducible nitric oxide synthase activity in T cell clones and T
      lymphocytes from naive and Leishmania major-infected mice.
AB  - Nitric oxide (NO) generated by the inducible isoform of nitric oxide synthase
      (iNOS) is implicated in a number of immunological processes including killing of
      intracellular parasites, suppression of T cell proliferation, production of
      cytokines and destruction of tissue in autoimmune diseases. Considering that
      cytokine-activated mouse macrophages, fibroblasts and endothelial cells are
      potent producers of NO, we investigated whether T cells, as central participants
      in immune responses, can also be activated for the release of NO. Neither
      thymocytes nor type 1 or type 2 T helper cell clones generated significant
      amounts of nitrite (the stable end product of NO in culture supernatants) when
      stimulated by T cell mitogens, cytokines or antigen in the presence of irradiated
      antigen-presenting cells. Similarly, T cells freshly isolated from mice acutely
      infected with the intracellular pathogen Leishmania major did not produce NO upon
      restimulation in vitro. The lack of NO production was not due to the expression
      of enzymatically inactive iNOS, as we were unable to detect any iNOS protein in
      activated T helper clones or in freshly isolated T cells from infected mice by
      Western (protein) blot analysis. Finally, we tested whether iNOS expression in T
      cells might be restricted to a minor subpopulation and therefore only detectable
      on a single cell level. After immunofluorescence staining of lymph node or spleen
      cells from infected mice with antibodies against iNOS, F4/80- or Thy-1-antigen,
      macrophages, but no T cells, were found to express iNOS. Thus, we have no
      evidence that activated T helper cell clones or T cells from L. major-infected
      mice are high producers of NO.

PMID- 8566006
TI  - Processing and presentation of type II collagen, a fibrillar autoantigen, by H-2q
      antigen-presenting cells.
AB  - Native type II collagen (CII) is a high molecular-weight fibrillar molecule which
      induces a chronic polyarthritis in mice expressing the H-2q haplotype. The
      present study was initiated to analyze the processing and the presentation of
      this nonglobular protein by H-2q antigen-presenting cells (APC). Efficiency of
      presentation was assessed by the ability of antigen-pulsed APC to activate
      collagen-specific CD4+ T cell hybridomas. Fixation of APC or the presence of
      chloroquine completely blocked the reactivity of the T cell hybrids to native,
      denatured and cyanogen bromide (CB) degraded CII, thus indicating the requirement
      of intracellular processing for adequate presentation of CII peptides to T cells.
      In the presence of various processing inhibitors (brefeldin A, leupeptin and N
      tosyl-L-phenylalanine chloromethylketone) stimulation of T hybrids by CII-pulsed
      APC was reduced, pointing to the need of newly synthesized class II molecules,
      the use of several intracellular compartments and the implications of different
      proteases in the generation of CII peptides. Peritoneal macrophages and, to a
      lesser extent, total spleen cells, presented native and denatured CII with higher
      efficiency than purified splenic dendritic cells, naive or even immune B cells
      from CII-primed mice. In contrast, these dendritic and B cells were fully
      competent to present intact ovalbumin to a specific T cell hybrid. The
      stimulation by dendritic cells and immune B cells was greater when CB peptides of
      CII were added instead of the native molecule. Similarly, the cleavage of CII was
      an absolute requirement for its presentation by epidermal cells and B cell
      lymphomas to the T cell hybridomas. Taken together, these findings emphasize the
      crucial role of intracellular processing for recognition of soluble CII, similar
      to most antigens. However, in contrast to ovalbumin, the size and fibrillar
      nature of the native CII molecule influences its capture by the APC, thus
      limiting the type of APC able to present this antigen.

PMID- 8566007
TI  - Role of tumor necrosis factor-alpha in the regulation of activated synovial T
      cell growth: down-regulation of synovial T cells in rheumatoid arthritis
      patients.
AB  - To characterize the role of tumor necrosis factor (TNF)-alpha in regulating
      synovial T cell growth, cell cycle progression associated with TNF-alpha in
      mitogen-activated synovial T cells of patients with rheumatoid arthritis (RA)
      were analyzed. After mitogen stimulation, the majority of synovial T cells in RA
      patients accumulated in S-phase. Anti-human TNF-alpha monoclonal antibody and
      soluble recombinant human TNF receptor (rhTNFR) can block S-phase accumulation.
      Furthermore, synovial fluid (SF) from RA patients was able to inhibit the
      proliferation of these S-phase-accumulated T cells. These data indicate that TNF
      alpha could regulate activated synovial T cell growth by driving them into S
      phase. Combined with the activities of other components of SF, TNF-alpha seems to
      play an important role in down-regulating activated synovial T cells in RA
      patients. In addition, the elevated level of soluble TNFR in the SFof disease
      active RA patients is believed to be associated with the promotion of synovial T
      cell responses.

PMID- 8566008
TI  - CD40-CD40 ligand interactions stimulate B cell antigen processing.
AB  - The interactions between B cell CD40 and T cell CD40 ligand (CD40L) have been
      shown recently to play an important role in T cell-dependent activation of B
      cells. Here, we show that the ligation of CD40 stimulates the processing of
      antigen by B cells. The activation of an antigen-specific T cell hybrid by B
      cells co-cultured with insect cells expressing recombinant CD40L or with a CD40
      specific monoclonal antibody requires less antigen and fewer B cells compared to
      control cells. The augmentation was observed both for processing initiated by
      antigen binding to and cross-linking the surface immunoglobulin, and processing
      of antigen taken up by fluid-phase pinocytosis. CD40 appears to affect a step in
      the intracellular processing of antigen, as CD40 has no effect on the
      presentation of an antigenic peptide which does not require processing. In
      addition, the CD40-induced augmentation of processing is not attributable to the
      effect of CD40 ligation on the cell surface expression of B7, LFA-1 or CD23. CD40
      ligation does not affect the biosynthesis of the class II EK molecules, and
      although ligation of CD40 induces B cell proliferation, the augmentation of
      processing does not require proliferation. The ability of CD40 to stimulate B
      cell antigen processing has the potential to influence significantly the outcome
      of antigen-dependent T cell-B cell interactions.

PMID- 8566009
TI  - The roles of perforin- and Fas-dependent cytotoxicity in protection against
      cytopathic and noncytopathic viruses.
AB  - In vitro, T cell-dependent cytotoxicity is mediated by two distinct mechanisms,
      one being perforin-, the other Fas-dependent. The contribution of both of these
      mechanisms to clearance of viral infections was investigated in mice for the non
      cytopathic lymphocytic choriomeningitis virus (LCMV) and the cytopathic vaccinia,
      vesicular stomatitis (VSV) and Semliki forest (SFV) viruses. Clearance of an
      acute LCMV infection was mediated by the perforin-dependent mechanism without
      measurable involvement of the Fas-dependent pathway. For the resolution of
      vaccinia virus infection and for resistance against VSV and SFV, however, neither
      of the two pathways was required. These data suggest that perforin-dependent
      cytotoxicity mediated by T cells is crucial for protection against non-cytopathic
      viruses, whereas infections with cytopathic viruses are controlled by nonlytic T
      cell-dependent soluble mediators such as cytokines (IFN-gamma against vaccinia
      virus) and neutralizing antibodies (against VSV and SFV).

PMID- 8566010
TI  - A human follicular lymphoma B cell line hypermutates its functional
      immunoglobulin genes in vitro.
AB  - The functional immunoglobulin (Ig) genes of B lymphocytes undergo somatic
      mutations during immune responses. These mutations modify the antigen binding
      site of the immunoglobulins, thereby enhancing the average affinity of the
      antibodies produced. The molecular mechanism underlying these B cell
      hypermutations remains unresolved, partly because it is difficult to grow normal
      B cells in long-term cell cultures and because there is no suitable transformed
      or malignant B cell line which generates mutations in its immunoglobulin genes in
      vitro. Here, we show that the recently established follicular lymphoma line HF
      1.3.4 generates somatic hypermutations in vitro at a high frequency of 0.7 x 10(
      6) mutations per base pair per generation in standard cell cultures (RPMI 1640 +
      5% fetal calf serum). This shows for the first time that B cell hypermutation can
      occur without T cells or T cell factors. The mutation frequency increased
      approximately tenfold to 1 x 10(-5) mutations/base pair/generation with B cell
      specific growth factors (interleukins-2 and -4 and three antibodies stimulatory
      to HF-1.3.4 cells). This HF-1.3.4 lymphoma line may help to elucidate the
      molecular mechanism of Ig gene hypermutation.

PMID- 8566011
TI  - Peptide anchor residue glycosylation: effect on class I major histocompatibility
      complex binding and cytotoxic T lymphocyte recognition.
AB  - This study extends our previous observation that glycopeptides bind to class I
      major histocompatibility complex (MHC) molecules and elicit carbohydrate-specific
      CTL responses. The Sendai virus nucleoprotein wild-type (WT) peptide (FAPGNYPAL)
      binds H-2Db using the P5-Asn as an anchor. The peptide K2 carrying a P5 serine
      substitution did not bind Db. Surprisingly, glycosylation of the serine (K2-O
      GlcNAc) with N-acetylglucosamine (GlcNAc), a novel cytosolic O-linked
      glycosylation, partially restored peptide binding to Db. We argue that the N
      acetyl group of GlcNAc may fulfil the hydrogen bonding requirements of the Db
      pocket which normally accomodates P5-Asn. Glycosylation of the P5-Asn residue
      itself abrogated binding similar to K2, probably for steric reasons. The peptide
      K2-O-GlcNAc readily elicited Db-restricted cytotoxic T lymphocytes (CTL), which
      did not cross-react with K2 or WT. However, all Db-restricted CTL raised against
      K2-O-GlcNAc cross-reacted strongly with another glycopeptide, K3-O-GlcNAc, where
      the GlcNAc substitution is on a neighboring P4-Ser. Furthermore, Db-restricted
      CTL clones raised against K2-O-GlcNAc or K3-O-GlcNAc displayed a striking TCR
      conservation. Our interpretation is that the carbohydrate of K2-O-GlcNAc not only
      mediates binding to Db, but also interacts with the TCR in such a way as to mimic
      K3-O-GlcNAc. This unusual example of molecular mimicry extends the known effects
      of peptide glycosylation from what we and others have previously reported:
      glycosylation may create a T cell neo-epitope, or, conversely, abrogate
      recognition. Alternatively, glycosylation may block peptide binding to MHC class
      I and finally, as reported here, restore binding, presumably through direct
      interaction of the carbohydrate with the MHC molecule.

PMID- 8566012
TI  - Mitochondrial perturbations define lymphocytes undergoing apoptotic depletion in
      vivo.
AB  - We have recently shown that lymphocyte apoptosis induced by dexamethasone or
      superantigens is accompanied by reduction of mitochondrial transmembrane
      potential (delta psi m) which precedes nuclear DNA fragmentation. Here, we
      demonstrate that fluorochromes such as 3,3' dihexyloxacarbocyanine iodide
      [DiOC6(3)] which measure delta psi m, or fluorochromes such as hydroethidine (HE)
      which measure mitochondrial superoxide anion production allow the identification
      of thymocytes or peripheral T lymphocytes which are eliminated by apoptosis in
      vivo. In mice bearing transgenic alpha/beta T cell receptor (TCR) specific for a
      class I-restricted male-specific peptide, the superoxide-mediated oxidation of HE
      into ethidium (Eth) is enhanced among thymocytes which are being deleted due to
      negative selection (CD4+ CD8+ cells expressing the transgenic TCR in male mice)
      or lack of positive selection (CD4+ CD8- thymocytes from female mice). delta psi
      m reduction and/or enhanced HE oxidation are also found when apoptosis is induced
      by a series of pathogenic agents. Thus, lethal irradiation provokes mitochondrial
      and nuclear signs of apoptosis, and both these alterations are absent in mice
      bearing a p53 null mutation, underlying the correlation between mitochondrial
      perturbation and nuclear apoptosis. Similarly, superantigen-triggered deletion of
      peripheral T cells in vivo is accompanied by enhanced HE-->Eth conversion and
      reduced DiOC6(3) uptake. More importantly, as compared to normal controls, CD4+
      or CD8+ cells from clinically asymptomatic human immunodeficiency virus-1 (HIV-1)
      carriers also contain a significantly elevated percentage of cells endowed with
      reduced DiOC6(3) uptake. In superantigen- and HIV-induced apoptosis, the
      percentage of T lymphocytes with a subnormal DiOC6(3) uptake is more important
      than that of cells marked by enhanced HE-->Eth conversion. In conclusion,
      mitochondrial alterations precede and/or accompany nuclear signs of apoptosis
      induced by physiological and a variety of different pathogenic agents in vivo.

PMID- 8566013
TI  - Altered Th1/Th2 balance associated with the immunosuppressive/protective effect
      of the H-2Ab allele on the response to allo-4-hydroxyphenylpyruvate dioxygenase.
AB  - The H-2Ab allele exerts a dominant down-regulatory effect on the anti-allo-HPPD
      (4-hydroxyphenylpyruvate dioxygenase) antibody response, through a hitherto
      unknown mechanism. In the present study, the allo-variable peptide bound to
      responder H-2Ak molecules with higher affinity than to H-2Ab ones, arguing
      against the operation of an affinity hierarchy. Quantitative polymerase chain
      reaction revealed differences in cytokine mRNA expression between suppressed and
      high-responder mice. Lymph node cells of responder but not suppressed mice
      contained high levels of interleukin (IL)-4 mRNA as early as 11 h post
      immunization and continued to do so for at least 8 days; this early burst was
      paralleled by a small burst in transforming growth factor (TGF)-beta mRNA level.
      Differences in IL-12 mRNA were not detected, although an early IL-12 effect could
      not be excluded. Interferon (IFN)-gamma appeared to contribute to the suppression
      at later time points. Early treatment of responder mice with anti-IL-4 monoclonal
      antibody (11B11) down-regulated the antibody response. The proliferative T cell
      response from hyperimmunized mice was reduced but still detectable in the
      presence of an H-2Ab allele. Thus, in the presence of this allele, the Th1
      response is enhanced and that of Th2 cells suppressed, apparently as a result of
      the bias of H-2Ab-restricted T cells in favor of the Th1 subset.

PMID- 8566014
TI  - Human T lymphocyte activation induces tyrosine phosphorylation of alpha-tubulin
      and its association with the SH2 domain of the p59fyn protein tyrosine kinase.
AB  - A glutathione-S-transferase-src-homology domain 2 (GST-SH2) fusion protein was
      employed to identify molecules interacting with the protein tyrosine kinase
      p59fyn. Among several proteins which bound to the fyn SH2 domain in lysates of
      human Jurkat T lymphocytes, alpha- and beta-tubulin were identified by N-terminal
      sequencing. Further analysis established that alpha-tubulin exists as a tyrosine
      phosphorylated protein in Jurkat cells, where it interacts with p59fyn, but not
      with p56lck. By contrast, in untransformed resting human T lymphocytes alpha
      tubulin is not detectable as a tyrosine phosphorylated protein. However,
      following T cell activation, it becomes rapidly phosphorylated on tyrosine
      residues and subsequently associates with the SH2 domain of fyn. Interestingly,
      constitutively tyrosine-phosphorylated alpha-tubulin that is able to interact
      with the fyn-SH2 domain is expressed in peripheral blood T lymphoblasts isolated
      from leukemic patients in the absence of external stimulation.

PMID- 8566015
TI  - In susceptible mice, Leishmania major induce very rapid interleukin-4 production
      by CD4+ T cells which are NK1.1-.
AB  - Susceptibility of BALB/c mice to infection with Leishmania major is associated
      with a T helper type 2 (Th2) response. Since interleukin-4 (IL-4) is critically
      required early for Th2 cell development, the kinetics of IL-4 mRNA expression was
      compared in susceptible and resistant mice during the first days of infection. In
      contrast to resistant mice, susceptible mice exhibited a peak of IL-4 mRNA in
      their spleens 90 min after i.v. injection of parasites and in lymph nodes 16 h
      after s.c. injection. IL-12 and interferon-gamma (IFN-gamma) down-regulated this
      early peak of IL-4 mRNA; the effect of IL-12 was IFN-gamma dependent. Treatment
      of resistant C57BL/6 mice with anti-IFN-gamma allowed the expression of this
      early IL-4 response to L. major. The increased IL-4 mRNA expression occurred in V
      beta 8, 7, 2- CD4+ cells in BALB/c mice and NK1.1- CD4+ cells in anti-IFN-gamma
      treated C57BL/6 mice. These results show that the NK1.1+ CD4+ cells, responsible
      for the rapid burst of IL-4 production after i.v. injection of anti-CD3, do not
      contribute to the early IL-4 response to L. major.

PMID- 8566016
TI  - Characterization of processing requirements and metal cross-reactivities in T
      cell clones from patients with allergic contact dermatitis to nickel.
AB  - Metal ions such as nickel, cobalt, copper and palladium are known to be potent
      sensitizers in humans, but the antigenic determinants created by these metals as
      well as the mechanisms of recognition by specific T cell clones are still not
      elucidated. In this paper, nickel-specific T lymphocyte clones were isolated from
      four patients exhibiting contact dermatitis to this metal. A panel of 42
      independent T cell clones was studied. They were shown to recognize nickel in the
      context of major histocompatibility complex (MHC) class II molecules and to
      belong to the CD4 subset. Using fixed autologous Epstein-Barr virus-transformed B
      cells as antigen-presenting cells (APC), we could distinguish two distinct groups
      of T cell clones on the basis of processing requirements: 40% of the T cell
      clones were strictly processing dependent, whereas the remaining 60% could
      proliferate in response to nickel even in the presence of glutaraldehyde-fixed
      APC. Furthermore, we present arguments indicating that individual Ni-specific T
      cell clones cross-react with some transition metals (e.g. Cu or Pd), but not with
      others (e.g. Co, Cr and Pt), presented by identical MHC class II molecules. These
      results thus provide an explanation for the multiple metal-reactivities observed
      in vivo in human patients: they indicate that for Cu and Pd, these co
      reactivities in vivo might be due to cross-reactivity at the clonal level. Our
      findings also suggest that this is not the case for cobalt allergy, which might
      result from cosensitization of the patient to cobalt in addition to nickel.

PMID- 8566017
TI  - The red cell LW blood group protein is an intercellular adhesion molecule which
      binds to CD11/CD18 leukocyte integrins.
AB  - Leukocyte adhesion involves the leukocyte-specific integrins CD11a/CD18,
      CD11b/CD18 and CD11c/CD18, which bind to intercellular adhesion molecules (ICAM).
      Three ICAM have been described, and are expressed on leukocytes and various other
      cells, but are absent from red cells. Here, we show that the red cell Landsteiner
      Wiener (LW) blood group glycoprotein is an ICAM which binds to the leukocyte
      specific integrins. This finding has important implications in red cell
      physiology.

PMID- 8566018
TI  - Interleukin-4-producing CD4+ NK1.1+ TCR alpha/beta intermediate liver lymphocytes
      are down-regulated by Listeria monocytogenes.
AB  - Experimental infection of mice with the intracellular bacterium, Listeria
      monocytogenes, provides a paragon model for immune defence dominated by T helper
      type 1 (Th1) responses. Potent production of interleukin (IL)-12 by infected
      macrophages is considered the determining factor in Th1 cell development. In
      contrast, it is assumed that IL-4 producers remain virtually unstimulated in
      listeriosis. In the liver, the major target organ of listeriosis, an unusual T
      lymphocyte population exists with the intriguing phenotype CD4+ NK1.1+ TCR
      alpha/beta intermediate (TCR alpha/beta int). Here we show that IL-4-producing
      CD4+ NK1.1+ TCR alpha/beta int liver lymphocytes are down-regulated early in
      listeriosis. We assume that curtailment of IL-4-producing CD4+ NK1.1+ TCR
      alpha/beta int liver lymphocytes promotes unconstrained development of Th1 cells
      which are central to protection against intracellular bacteria.

PMID- 8566019
TI  - Clustered and interspersed gene families in the mouse immunoglobulin kappa locus.
AB  - Although numerous solitary germ-line V kappa genes and two small V kappa
      contiguously cloned gene regions (contigs) are known, no attempts to
      systematically elucidate the structure of the kappa locus of the mouse have been
      reported so far. As a first step to this aim we screened a cosmid library of
      C57BL/6J mouse DNA with 18 probes that are more or less specific for the
      different V kappa gene families. Ninety-one V kappa gene-containing cosmid clones
      were characterized by detailed restriction mapping and hybridizations. Several
      contigs were constructed from overlapping clones. The contigs and the still
      unlinked cosmid clones cover 1.6 Mb. Many of the cosmid clones were localized on
      chromosome 6 where the kappa locus is known to reside; no evidence for the
      existence of dispersed V kappa genes (orphons) was obtained. Eighty-five strong
      hybridization signals were assigned to distinct V kappa gene families, while for
      11 weak signals the assignment was less definite. As to the distribution of gene
      families within the locus the following situation emerged: there are both, groups
      of genes which belong to one V kappa gene family ("clusters") and groups in which
      genes of different families are interspersed. The interspersion of gene families
      seems to be more pronounced than has been assumed so far. Additional V kappa
      genes which are known to exist will have to be isolated from other gene libraries
      of the same mouse Ig kappa haplotype.

PMID- 8566020
TI  - Malignant B lymphocytes from non-Hodgkin's lymphoma induce allogeneic
      proliferative and cytotoxic T cell responses in primary mixed lymphocyte
      cultures: an important role of co-stimulatory molecules CD80 (B7-1) and CD86 (B7
      2) in stimulation by tumor cells.
AB  - We analyzed the stimulating capacities of malignant B cells from non-Hodgkin's
      lymphomas (NHL) to induce an allogeneic response in primary mixed lymphocyte
      reaction (MLR). T cells purified from a single healthy donor (KS) were used to
      compare the responses induced by either malignant or hyperplastic cells.
      Malignant B cells induced strong proliferation of KS cells independently of their
      level of expression of adhesion molecules. The KS cells after MLR were
      predominantly CD3+, CD25+, HLA-DR+, Ki67+ and CD45RO+ T cells, and the CD4/CD8
      ratio was heterogeneous (from 0.8 to 2.7). To investigate the role of co
      stimulatory molecules CD80 and CD86 for the stimulatory capacities of B cells,
      the expression of both molecules was analyzed before and during the MLR. Most
      fresh malignant B cells were negative for CD80 and CD86, whereas co-cultured B
      cells expressed high levels of both molecules. This expression was crucial for T
      cell proliferation, since monoclonal antibodies directed against CD80 and CD86
      completely abrogated the MLR. We also report that KS responding cells at the end
      of co-culture were able to lyse fresh B cells used as stimulator cells to
      different extents (from 10 to 51%), and the level of lysis was enhanced after PMA
      activation of the target cells. Inhibition experiments using CD8 and CD4 mAb
      showed that effector cells were mainly CD8+. This report is the first to describe
      the accessory function of human malignant B cells from NHL and their sensitivity
      to lysis mediated by CD8+ T cells, and suggests new strategies for the
      development of antitumor immunity in NHL.

PMID- 8566021
TI  - The role of perforin-expression by granular metrial gland cells in pregnancy.
AB  - The pregnant uterus of humans and rodents contains a population of granulated
      lymphoid cells, which, in the mouse, are called granular metrial gland (GMG)
      cells and have been described to express high levels of perforin. Since there is
      evidence for cytolytic activity of these cells and since perforin is a crucial
      effector molecule for the lytic action of cytotoxic T cells and natural killer
      cells, we evaluated the function of perforin in the pregnant uterus by using
      perforin-deficient mice. Perforin-deficient female mice were found to reproduce
      as efficiently as normal control females when bred either with syngeneic or
      allogeneic males. However, perforin-deficient mice differed from normal mice in
      that the frequency of GMG cells was significantly higher within maternal blood
      spaces and within several compartments of the feto-maternal interface.
      Proliferating GMG cells, identified by [3H] thymidine incorporation, were
      observed during more advanced stages of pregnancy when compared to normal
      controls. In contrast to normal mice, perforin-deficient mice did not display GMG
      cells attached to degenerating trophoblasts; instead perforin-deficient GMG cells
      were often observed in association with small maternal lymphocytes. In addition,
      the lack of transmission of lymphocytic choriomeningitis virus from infected
      pregnant perforin-deficient mice to the fetuses argued against a role of perforin
      expression by GMG cells in prevention of virus transmission from the mother to
      the fetus. Our data indicate that functional perforin is not necessary for
      successful pregnancies. The morphological changes in the pregnant uterus of
      perforin-deficient mice might, however, point to a certain, as-yet undefined
      function of perforin in the uterus of pregnant normal mice, which is functionally
      compensated in perforin-deficient mice.

PMID- 8566022
TI  - Down-regulation of class II major histocompatibility complex molecules on antigen
      presenting cells by antibody fragments.
AB  - Certain HLA class II-specific monoclonal antibodies (mAb) cause up to 90%
      decrease in the cell surface expression of class II molecules. This down
      regulation is isotype-specific, i.e. DR-specific mAb do not affect the expression
      of DP and DQ molecules. However, antibodies binding to one DR allotype down
      regulate both allotypes in heterozygous antigen-presenting cells (APC),
      indicating that the phenomenon is not a direct consequence of ligation. All down
      regulating mAb identified recognize the first (peptide binding) domains of class
      II heterodimers, and strongly inhibit the activation of class II-restricted human
      T cells in vitro. Conversely, non-down-regulating mAb fail to inhibit T cell
      activation, and most of them (four out of five) recognize class II second
      domains. Down-regulating antibodies are cytotoxic for B lymphoblastoid cell lines
      and for a small proportion of normal activated B cells. Their F(ab')2 fragments
      mediate both down-regulation and cytotoxicity, whereas the monovalent Fab
      fragments are not cytotoxic, but retain the down-regulatory and T cell inhibitory
      properties. These findings raise the possibility of a class II major
      histocompatibility complex-specific, antibody-based immunosuppressive therapy
      without cytotoxic side effects.

PMID- 8566023
TI  - Identification of an ionomycin/cyclosporin A-responsive element within the human
      T cell receptor gamma enhancer.
AB  - Activation through the Ca2+/calcineurin pathway is essential to the transcription
      of many cytokine genes. The conserved cis-acting sequence, GGAAAA, and
      transcription factors binding to this sequence are involved in the response to
      increased intracellular Ca2+ concentrations. Here we report the identification
      and importance of the same sequence in a non-cytokine gene, the human T cell
      receptor gamma (TCRG) enhancer. Results from site-directed mutations and
      electrophoretic mobility shift assays strongly suggest that this sequence
      mediates the ionomycin-induced activation of the TCRG enhancer. Our studies
      provide an explanation for a previous observation that TCRG mRNA levels, but not
      mRNA levels for T cell receptor alpha and -beta, are increased by ionomycin
      treatment.

PMID- 8566024
TI  - Precursor cells to CD3-intermediate (CD3int) liver mononuclear cells in the adult
      liver: further evidence for the extrathymic development of CD3int liver
      mononuclear cells.
AB  - Liver mononuclear cells (LMNC) can be divided into CD3-high positive (CD3hi), CD3
      intermediate positive (CD3int) and CD3- populations. CD3int LMNC, but not CD3hi
      LMNC, are considered to be extrathymically derived because they are found in the
      liver of nude mice and adult thymectomized lethally irradiated bone marrow
      chimeras. CD3int LMNC express NK1.1 and show a skewed T cell receptor (TCR) V
      region repertoire with relatively high levels of V beta 8 and V alpha 14
      expression, further suggesting that they belong to a different lineage from
      conventional T cells, which lack NK1.1 expression and V region skewing. Since the
      liver has been proposed to be a site of extrathymic T cell differentiation in
      adult mice, we analyzed LMNC for the presence of T cell precursors. CD3- LMNC
      contained CD4- CD8- cells and CD4lo CD8- cells. Reverse transcription-polymerase
      chain reaction analysis showed both CD3- populations express the recombination
      activating gene -1, which is indispensable in gene rearrangement of TCR and
      expressed by thymic T cell precursors. Furthermore, when electronically sorted
      CD3- LMNC were cultured in medium without any feeder cells or exogenously added
      cytokines for 24 h, CD3int cells, but not CD3hi cells, appeared. These results
      suggest that the adult liver contains T cell precursors that lack the expression
      of the CD3/TCR complex, but are strongly committed to differentiate into
      extrathymic liver CD3int T cells.

PMID- 8566025
TI  - Detection of restricted isoform expression and tyrosine phosphatase activity of
      CD45 in murine dendritic cells.
AB  - CD45 is a cell surface transmembrane tyrosine phosphatase. It is expressed as
      distinct protein isoforms via alternative splicing of exons 4, 5 and 6. In T and
      B lymphocytes, CD45 is thought to play a critical role in antigen-dependent
      signaling through their respective antigen receptor complexes. However, the
      isoform expression and enzymatic activity of CD45 in other leukocytes remains
      largely unknown. Here, we examine the isoform expression and phosphatase activity
      of CD45 in murine dendritic cells (DC). Flow cytometric double-labeling analysis
      and biochemical analysis of purified splenic DC CD45 demonstrate that DC express
      both the CD45RB and CD45R0 isoforms. Flow cytometric analyses of freshly isolated
      splenic DC and thymic DC also indicate the expression of CD45RB and CD45R0 on
      these DC populations. In addition, we find that purified splenic DC CD45
      possesses a high level of intrinsic tyrosine phosphatase activity. These data
      therefore establish the restricted isoform expression pattern of CD45 in murine
      DC and demonstrate that cells lacking specific antigen receptor complexes have
      active tyrosine phosphatase activity associated with CD45.

PMID- 8566026
TI  - Carrier-induced epitope-specific regulation and its bypass in a protein-protein
      conjugate.
AB  - In the course of clinical trials on a birth control vaccine, it was found that
      some of the immunized women responded poorly to booster immunizations. This
      vaccine consists of a dimer of the beta chain of human chorionic gonadotropin
      (beta hCG) and the alpha chain of ovine luteinizing hormone (alpha oLH), linked
      to tetanus toxoid (TT) as a carrier. Changing this carrier to diphtheria toxoid
      resulted in reversion to high anti-hCG antibody titers, indicating the extent to
      which the carrier influences anti-ligand responses in this system. The
      suppression of anti-hCG responses after booster immunizations was reminiscent of
      the phenomenon of carrier-induced, epitope-specific regulation. In a mouse model
      designed to test the effects of preimmunization with TT on anti-hCG responses, we
      found that a single preimmunization with TT causes reduced anti-hCG antibody
      responses in two out of four mouse strains, while anti-alpha oLH antibody
      responses were not affected by the preimmunization with TT. This is particularly
      interesting considering that beta hCG and alpha oLH were not presented when
      linked separately to TT. In an effort to devise a strategy to circumvent this
      carrier-induced, ligand-specific hyporesponsiveness, we investigated the
      effectiveness of a synthetic T helper epitope from TT as carrier. We show that
      preimmunization with TT causes a less profound reduction in anti-hCG titers if
      the preimmunized mice are subsequently injected with alpha oLH-beta hCG
      conjugated to a synthetic tetanus toxin peptide recognized by TT-induced and
      peptide-induced T cells.

PMID- 8566028
TI  - B1 and B2 cells differ in their potential to switch immunoglobulin isotype.
AB  - The ability of purified B1a (Ly-1 B) and B2 cells to switch immunoglobulin
      isotype was assessed by limiting dilution analysis in two in vitro culture
      systems. When stimulated in the presence of interleukins-4 and -5 by either
      lipopolysaccharide or CD40 ligand, the frequency of IgG1 precursors in the B1a
      population was at most one third that of IgM precursors. In B2 cells, however,
      the frequency of IgG1 precursors was up to seven times that of IgM precursors.
      B1a cells were shown to respond to interleukin-4 by virtue of up-regulating major
      histocompatibility complex class II expression when exposed to the cytokine,
      precluding non-responsiveness as a reason for not switching to IgG1. Indeed,
      interleukin-4 was found to specifically induce transcription of the germ-line
      IgG1 constant region locus in B1a cells as it did in B2 cells. Collectively these
      results suggest that the ability of B1 cells to respond to isotype switch
      commitment factors such as interleukin-4 may be secondary to the production of
      IgM by these cells.

PMID- 8566027
TI  - Two signaling pathways can lead to Fas ligand expression in CD8+ cytotoxic T
      lymphocyte clones.
AB  - As shown previously, a given cytotoxic T lymphocyte (CTL) clone (KB5.C20) could
      be induced to express the Fas ligand (FasL) by either T cell receptor (TCR)
      engagement or phorbol 12-myristate 13-acetate (PMA)/ionomycin stimulation. In
      contrast, another CTL clone (BM3.3) has now been found to exert Fas-based
      cytotoxicity only after TCR engagement, but not after PMA/ionomycin stimulation.
      This suggested the existence of a PMA-insensitive, antigen-induced pathway
      leading to FasL expression. The inability of PMA to promote Fas-based
      cytotoxicity in BM3.3 cells was correlated with a defect in expression of the
      classical protein kinase C (PKC) isoforms alpha and beta I. In KB5.C20 cells
      depleted of PMA-sensitive PKC isoforms and thus no longer responsive to PMA, Fas
      based cytotoxicity could still be induced via the TCR/CD3 pathway. On the other
      hand, a requirement for phosphatidylinositol-3 kinase (PI3K) selectively in this
      TCR/CD3-induced pathway was demonstrated by specific inhibition with wortmannin.
      These results suggest that FasL expression when induced via the TCR/CD3 involves
      PI3K, and when induced by PMA/ionomycin requires the expression of PMA-sensitive
      PKC isoforms absent in clone BM3.3. Additional data suggest that in neither case
      was NF-kappa B activation implicated in FasL expression.

PMID- 8566029
TI  - Interleukin-2 down-modulates memory T helper lymphocyte development during
      antigenic stimulation in vitro.
AB  - Using an in vitro antigenic stimulation model of murine spleen cells in the
      presence of the immunosuppressor cyclosporin A (CSA) we have previously reported
      that not only does this drug not interfere with the differentiation of T
      lymphocytes into memory cells it appears to favor this differentiation (Motta, I.
      et al., Eur. J. Immunol. 1991. 21:551). Because CSA blocks interleukin-2 (IL-2)
      gene expression, we have analyzed the effect of this cytokine on memory T helper
      cell development. Murine splenic cells were primed for 6 days with sheep red
      blood cells (SRBC) in protocols in which either IL-2 was not produced or its
      biological activity was neutralized by anti-IL-2 receptor (R) antibodies. The
      helper function of the recovered T cells was revealed by their capacity to help
      virgin B splenocytes produce anti-SRBC antibodies upon challenge in vitro. We
      found that CD4+ cells primed in the absence of IL-2, provoked either by IL-2 gene
      transcription blockade by CSA or by treatment with anti-IL-2R antibodies, afford
      the best helper functions. These cells exhibit a memory-type phenotype
      characterized by the low expression of the MEL-14 marker and the high expression
      of the CD44 marker. Evidence is also presented that memory T helper cells
      originate in part from naive subset displaying the MEL-14hi phenotype. The
      pattern of expression of the genes encoding different cytokines (IL-2, IL-4, IL-5
      and interferon-gamma) following a secondary antigenic stimulation shows that the
      helper function of the cells primed in the absence of IL-2 correlates with the up
      regulation of the IL-2 and the IL-5 genes. From these data, we conclude that IL-2
      plays a major role in the control of memory T helper cell induction.

PMID- 8566030
TI  - Presentation of endogenous viral proteins in association with major
      histocompatibility complex class II: on the role of intracellular
      compartmentalization, invariant chain and the TAP transporter system.
AB  - Major histocompatibility complex (MHC) class II-associated antigen presentation
      is mainly linked to processing of exogenous antigens upon cellular uptake by
      endocytosis, but has also been observed for endogenously synthesized antigens. We
      have studied the MHC class II-associated presentation of the endogenously
      synthesized membrane associated glycoprotein (GP) and the cytosolic nucleoprotein
      (NP) of lymphocytic choriomeningitis virus (LCMV) in professional antigen
      presenting cells (APC) of mice. Since LCMV is a noncytopathic virus and minimally
      affects cellular protein synthesis, it is a convenient virus for the study of
      antigen presentation. In contrast, most other studies assessing class II
      associated presentation of endogeneously synthesized viral antigens used
      cytolytic viruses such as vaccinia, measles and influenza virus, which
      drastically interfere with host cell functions. In addition, most studies were
      performed using non-professional APC. We found that class II-associated
      presentation of endogenously synthesized membrane associated LCMV-GP was
      efficient and could not be inhibited by chloroquine or leupeptin. Neither the
      transporter associated with processing (TAP) system nor the invariant chain (Ii)
      were significantly involved in this process. In contrast, MHC class II-associated
      presentation of endogenously synthesized cytosolic LCMV-NP was not observed even
      in Ii-deficient APC. Thus, MHC class II loading of endogenously synthesized LCMV
      GP apparently does not require processing in acidic endosomal compartments as
      defined by chloroquine and leupeptin insensitivity. Furthermore, although the TAP
      molecules transport peptides of up to 15 amino acids in length, which potentially
      could bind to MHC class II molecules in the endoplasmic reticulum, such a process
      apparently does not occur for either the glycoprotein or the nucleoprotein.
      Therefore, the subcellular localization of an endogenously synthesized protein
      influences crucially whether or not MHC class II loading can occur independently
      of the acidic compartments usually involved in MHC class II loading.

PMID- 8566031
TI  - The Yaa gene-mediated acceleration of murine lupus: Yaa- T cells from non
      autoimmune mice collaborate with Yaa+ B cells to produce lupus autoantibodies in
      vivo.
AB  - The BXSB Y chromosome-linked mutant gene, Yaa, promotes autoimmune responses in
      mice predisposed to a lupus-like autoimmune disease. We have previously shown
      that a cognate interaction of T cells with B cells expressing the Yaa gene
      appears to be responsible for the accelerated production of autoantibodies. To
      investigate whether T cells that provide help for autoantibody production by Yaa+
      B cells need to express the Yaa gene, we have made radiation bone marrow chimeras
      containing two sets of T and B cells from mice with or without the Yaa gene and
      differing by the Thy-1 and Igh allotypes. We then determined autoantibody
      production following the selective elimination of T cells of Yaa+ origin by
      treating mice with allele-specific anti-Thy-1 monoclonal antibody. Our results
      demonstrated that the selective production of autoantibodies by Yaa+ B cells in
      Yaa(+)-Yaa- double bone marrow chimeras can be mediated as efficiently by T cells
      from non-autoimmune mice lacking the Yaa gene as by T cells from autoimmune mice
      bearing the Yaa gene. This indicates that T cells from non-autoimmune Yaa- mice
      are capable of providing help for autoimmune responses by collaborating with Yaa+
      B cells. These data thus strongly suggest that the Yaa gene defect is not
      functionally expressed in T cells, but only in B cells, and contrast with
      parallel experiments in the lpr model, in which defects of the Fas antigen in
      both T and B cells are crucial for the lpr gene-mediated promotion of
      autoantibody production.

PMID- 8566032
TI  - CD14lowCD16high: a cytokine-producing monocyte subset which expands during human
      immunodeficiency virus infection.
AB  - Infection with the human immunodeficiency virus HIV-1 is associated with the
      expansion of a CD14lowCD16high monocyte subset in peripheral blood. This subset,
      which represents a minor subpopulation of monocytes in healthy individuals,
      increases during HIV infection and, in patients with AIDS, may represent up to
      40% of the total circulating monocyte cell population. The CD14lowCD16high
      circulating monocytes co-express MAX.1, p150,95 and HLA-DR which are typical of
      tissue macrophage markers. These cells also express higher levels of
      intracellular interleukin (IL)-1 alpha and tumor necrosis factor (TNF)-alpha than
      the CD14highCD16low monocyte population from the same patients. The
      CD14lowCD16high cells also express low levels of CD35, CD11a and CD4 in common
      with normal monocytes. When cultured in vitro, monocytes from HIV-seropositive
      individuals differentiated within a few hours into an elongated fibroblastoid
      shape characteristic of migratory cells. Our results suggest that the expansion
      of the CD14lowCD16high monocyte subset, which produce high amount sof TNF-alpha
      and IL-1 alpha, may participate in the immune dysfunction observed during HIV
      infection.

PMID- 8566033
TI  - Bacterial superantigen specificities of mouse T cell receptor V beta 20.
AB  - The study of the mouse T cell receptor (TcR) beta chain repertoire in BALB/c
      thymocytes led to the identification of the V beta 20 gene segment. The
      expression of V beta 20 estimated at the transcriptional level differs among
      mouse strains, suggesting clonal deletion. In the present study, we reconstituted
      by transfection functional TcR using the V beta 20 segment with different V alpha
      segments and studied the action of superantigen toxins. The V beta 20
      transfectant T cells are activated by staphylococcal enterotoxins A and E (SEA
      and SEE) but not by the other tested toxins. The activation is dependent on the
      presence of cells expressing major histocompatibility complex class II molecules.
      Different HLA DR alleles can present the bacterial toxins, establishing that they
      interact with TcRV beta 20 as superantigens. Moreover, the V alpha domain
      associated with the V beta 20 domain has an influence on the response to these
      toxins. The fact that V beta 20 is recognized by SEA and SEE, although both
      toxins are known to interact with different sets of V beta, suggests the presence
      of different TcR binding sites on the toxins.

PMID- 8566034
TI  - Differential requirements of CD45 for lymphocyte development and function.
AB  - CD45 exon 6-deficient mice show a profound block of thymocyte development at a
      transitional differentiation step from immature CD4+ CD8+ to mature single
      positive cells. Only a few T lymphocytes are observed in the periphery of such
      animals, but B cell development is not affected. We investigated whether mature B
      lymphocytes in CD45 exon 6-deficient mice have normal functions in the absence of
      CD45 expression and show here that CD45-defective B lymphocytes from CD45 exon 6
      deficient mice have intact B lymphocyte functions, including T-dependent and T
      independent antigen-specific antibody production and class switching in vivo if
      normal CD4+ T lymphocytes were adoptively transferred into the mutant mice. From
      these results, we conclude that CD45 expression on B lymphocytes is not essential
      for B cell responses following antigen stimulation in vivo. However, CD4+ T
      helper function was severely diminished in CD45 exon 6-deficient mice, suggesting
      that the requirements of CD45 molecules in antigen-specific response and
      development are different between T and B lymphocytes.

PMID- 8566035
TI  - Definition of sites on HLA-DR1 involved in the T cell response to staphylococcal
      enterotoxins E and C2.
AB  - We have exploited the relative inefficiency of interaction between staphylococcal
      enterotoxins, SEE or SEC2, and H-2Ek compared to HLA-DR1 molecules to deduce
      which regions of the major histocompatibility complex (MHC) class II molecule are
      involved in the T cell response to these superantigens. Transfectants expressing
      hybrid DR/H-2E MHC class II molecules were used to present SEE to the T cell
      receptor V beta 8.1-expressing Jurkat cell line, and SEC2 to human peripheral
      blood T cells. For SEE, the critical region of the class II molecule for T cell
      reactivity and for binding was the beta 1 domain alpha-helix. The functional data
      were corroborated by measurements of direct binding. Sequence comparison between
      DR and H-2E raised the possibility that the glutamic acid at position 84 in the
      beta chain of H-2Ek, in place of glycine was responsible for the observed
      functional effects. This suggestion was supported by the finding that DQw2
      (glutamine at 84) transfectants supported the SEE response much more efficiently
      than DQw6 that has glutamic acid at this position. In addition, amino acid
      substitutions at either position 36 or 39 in the DR alpha 1 domain abolished T
      cell reactivity without any obvious alteration in binding. For SEC2, use of
      transfectants expressing exon-shuffled alpha and beta chain genes showed that
      replacement of the alpha 1, alpha 2 and beta 1 domains with H-2E sequence
      inhibited the presentation of SEC2. Similarly, the substitutions at positions 36
      and 39 in the alpha 1 domain abolished the T cell response to SEC2. Taken
      together, these data may be best explained by a model in which these two toxins
      have primary binding sites on the beta 1 domain (SEE) and the alpha 1 and alpha 2
      domains (SEC2), but by virtue of a secondary binding site on the opposite surface
      of the class II molecule, cross-link two adjacent DR molecules. Such cross
      linking may be important in the induction of T cell reactivity.

PMID- 8566036
TI  - T helper cell-independent neutralizing B cell response against vesicular
      stomatitis virus: role of antigen patterns in B cell induction?
AB  - The neutralizing antibody response against vesicular stomatitis virus (VSV) was
      studied to analyze conditions necessary for induction of mature B cells. The
      glycoprotein of VSV (VSV-G) is expressed as repetitive epitopes that are in a
      rigid densely packed paracristalline form in the virus envelope; in contrast, VSV
      G is present in a mobile randomly ordered form on infected cells and in micelles.
      We found that the rigid, paracristalline form of VSV-G spaced about 5-10 mm on
      VSV virons induced potent primary and secondary neutralizing B cell responses
      which were independent of T helper cells, whereas the more randomly distributed,
      mobile forms of VSV-G induced primary and secondary B cell responses that were
      more tightly controlled by T helper cells. These data suggest that (i) cross
      linking is a critical signal for B cell activation and antibody production, and
      that this signal alone does not necessarily anergize or delete mature B cells,
      (ii) the more regularly and rigidly ordered in a distance of 5-10 nm repetitive
      identical antigenic determinants are, the less are primary and secondary B cell
      responses controlled by T cells. We therefore propose that B cells take antigen
      organization as a marker for foreigness.

PMID- 8566037
TI  - Supportive cellular elements for hepatic T cell differentiation: T cells
      expressing intermediate levels of the T cell receptor are cytotoxic against
      syngeneic hepatoma, and are lost after hepatocyte damage.
AB  - Extrathymic T cells exist in the liver and are often seen in close contact with
      Kupffer cells in the hepatic sinusoids. Since selective depletion of Kupffer
      cells has become possible by using liposome-encapsulated clodronate, it was
      investigated whether elimination of Kupffer cells influences the level of
      extrathymic T cells in the liver. Extrathymic T cells were identified as
      interleukin-2 receptor beta-chain (IL-2R beta) intermediate TCR (TCRint) cells by
      two-color staining for CD3 or T cell receptor (TCR) and IL-2R beta. The
      elimination of Kupffer cells did not significantly affect levels of TCRint cells
      up to 7 days after treatment. We then examined monocyte colony stimulating factor
      (M-CSF)-deficient op/op mice (low levels of Kupffer cells). Extrathymic T cells
      both in the liver and spleen of these mice were detected at a level comparable to
      that of control mice. Since extrathymic T cells in the liver are sometimes
      located in the parenchymal space, the relationship between extrathymic T cells
      and hepatocytes was then examined. Electron microscopy revealed that some hepatic
      T cells adhered directly to hepatocytes. When hepatocytes were damaged by a
      single injection of CCl4, hepatocyte death and subsequent hepatic fibrosis were
      induced. Beginning 3 days after injection, CD3int cells, but not other type of
      cells, decreased prominently. Purified CD3int cells, as well as whole lymphocytes
      in the liver, were cytotoxic against syngeneic hepatoma. In parallel with the
      above-mentioned hepatic damage, the cytotoxic activity of lymphocytes against
      such targets was impaired in the liver. These results suggest that extra-thymic
      generation of TCRint cells and their acquisition of cytotoxic function are
      relatively independent of Kupffer cells, but are dependent on hepatocytes.

PMID- 8566038
TI  - Expression of the complement alternative pathway by human myoblasts in vitro:
      biosynthesis of C3, factor B, factor H and factor I.
AB  - In this study, we demonstrate expression in vitro of complement alternative
      pathway components C3, factor B, factor H and factor I by normal human myoblasts
      and human rhabdomyosarcoma cell lines CRL1558 and HTB153. Proteins in culture
      supernatants were detected by Western (protein) blot analysis and biosynthetic
      labeling followed by immunoprecipitation experiments, and quantified by ELISA.
      Newly secreted proteins were structurally and functionally similar to their serum
      counterparts. An additional polypeptide of 43 kDa with factor H immunoreactivity
      was detected, which could correspond to the N-terminal truncated form found in
      plasma. Protein expression was correlated with mRNA expression by reverse
      transcriptase-polymerase chain reaction analysis. The major proteins of
      complement alternative pathway C3, factor B and factor H were produced
      constitutively by skeletal muscle cells at a rate of 50 to 150 ng/10(6) cells/ml
      and factor I was expressed 20 ng/10(6) cells/ml. These syntheses in vitro were
      regulated by inflammatory cytokines. Interferon-gamma significantly upregulated
      C3, factor B and factor H expression, but had no effect on factor I production.
      Interleukin-1 beta strongly enhanced C3 and factor B production and had a weak
      enhancing or no effect on factor I and factor H secretion. Human myoblast cell
      lines constitute an interesting model to analyze complement biosynthesis by human
      skeletal muscle cells. Local complement expression by skeletal muscle in vivo may
      be implicated in some muscular inflammatory or pathological processes.

PMID- 8566039
TI  - Long-term humoral and cellular immunity induced by a single immunization with
      replication-defective adenovirus recombinant vector.
AB  - This study examines the suitability of replication-defective adenovirus vectors
      for engineering recombinant vaccines. The immunological abilities and limitations
      of E1-deleted adenoviruses containing the lacZ gene (Ad-beta-gal) were
      investigated by examining the humoral and cellular immune responses to the beta
      galactosidase protein. BALB/c mice (H-2d) were given in a single injection of
      recombinant adenovirus. The cytotoxic T lymphocyte (CTL) response of spleen cells
      was evaluated. Recognized target cells were H-2d-derived tumor cells transfected
      by the lac Z gene, or incubated with the 876-884 beta-galactosidase peptide known
      to be restricted by the Ld molecule of the major histocompatibility complex. A
      long-lasting beta-galactosidase-specific cytotoxic T cell response was obtained.
      By contrast, CTL from mice immunized with the Ld-restricted peptide were less
      specific for the endogenous epitope presented by the transfectants expressing
      beta-galactosidase. Ad-beta-gal-immunized mice were also protected against an
      intra-cerebral challenge with a recombinant vaccinia virus expressing the lac-Z
      gene. These results suggest that Ad-beta-gal-induced CTL have protective
      abilities in vivo. The induction of beta-galactosidase-specific T helper
      lymphocytes and humoral IgG responses were also examined. A proliferative
      response occurred only late after immunization and the primed T lymphocytes
      produced interleukin-2, but no interleukin-4. A humoral IgG response to the beta
      galactosidase protein was detected 15-30 days after a single immunization and
      remained stable for 6 months without boosting. Lastly, we followed the evolution
      of the immune response over the course of successive immunizations. The magnitude
      and kinetics of the cellular and humoral responses were similar to those obtained
      after a single immunization. Consistent with these observations, an adenovirus
      specific neutralizing antibody response was detected as early as the second
      immunization. Thus, a single immunization with a replication-defective adenovirus
      recombinant vector induces long-lasting humoral and cellular immune responses
      specific to the transgene product.

PMID- 8566040
TI  - Interleukin-6 signal transducer gp130 has specific binding sites for different
      cytokines as determined by antagonistic and agonistic anti-gp130 monoclonal
      antibodies.
AB  - The cytokines interleukin (IL)-6, IL-11, ciliary neurotrophic factor (CNTF),
      leukemia inhibitor factor (LIF), oncostatin M (OSM) and probably the recently
      cloned cytokine cardiotrophin-1, signal, in combination with their specific
      receptors, through the common signal transducer gp130. Here, we report that the
      signaling activities of IL-6, IL-11, CNTF and OSM/LIF can be specifically blocked
      by different anti-gp130 monoclonal antibodies (mAb). Furthermore, we found two
      mAb, B-P8 and B-S12, which directly activate gp130 independently of the presence
      of cytokines or their receptors. This agonistic activity includes induction of
      cytokine-dependent cell proliferation and stimulation of acute-phase protein
      synthesis in liver cells. Compared to B-P8 mAb, the B-S12 mAb exhibited the
      strongest agonistic activity, while both mAb are synergistic in their action.
      This activity could not be blocked by inhibiting mAb against IL-6 and the IL-6
      receptor. In contrast to F(ab')2 of B-S12 which still could activate gp130, Fab
      fragments completely lost their agonistic activity. Activation by tyrosine
      phosphorylation of the transcription factors Stat1 and APRF/Stat3 was also
      induced by B-S12 and B-P8, suggesting that both mAb induce homodimerization of
      gp130. Since hematopoietic stem cells express gp130 on their plasma membrane, it
      was anticipated that the agonistic anti-gp130 mAb could stimulate the
      proliferation of these stem cells. Indeed, B-S12 and B-P8 were able to stimulate
      CD34+ cells. In summary, our data show for the first time that mAb against gp130
      can specifically block the action of distinct IL-6-type cytokines that signal
      through gp130. Such mAb might be of great value for therapeutic applications in
      diseases where a single cytokine action needs to be inhibited. In addition, the
      agonistic gp130 mAb may be used as growth factors for maintenance and expansion
      of stem cells prior to grafting.

PMID- 8566042
TI  - Tolerance and immunity to the inducible self antigen C-reactive protein in
      transgenic mice.
AB  - The understanding of immunological tolerance has been greatly aided by the
      development of transgenic animal models in which expression of a specific T cell
      receptor (or B cell receptor) and its cognate self antigen is experimentally
      controlled. In most cases, expression of the self antigen was constitutive and
      did not allow for variation of its time- and dose-dependent expression pattern,
      parameters which are known to influence the balance of tolerance versus immunity.
      We describe a transgenic model in which expression of human C-reactive protein
      (hCRP), an acute-phase protein, is tightly controlled at basal levels (female
      mice express around 10(-9) M and male mice 5 x 10(-7) M circulating hCRP) and is
      highly inducible (induction factor of 25-500). T cells from C57BL/6 mice
      recognize two epitopes of hCRP termed A (residues 79-95) and B (residues 87-102).
      Different efficacies of presentation in vitro and in vivo identify epitope A as
      sub-dominant and epitope B as dominant. T cells of non-induced hCRP transgenic
      mice are tolerant to the dominant epitope, but reactive to the subdominant
      epitope. A hCRP-specific IgG antibody response is detectable in transgenic mice,
      but is weaker than in littermates. Upon induction of hCRP, both T cell epitopes
      are presented by thymic and splenic antigen-presenting cells (APC) in vivo.
      Kinetics of presentation by splenic APC closely match serum kinetics of hCRP,
      whereas presentation in the thymus is considerably prolonged. This model enables
      epitope-specific T cell tolerance to be studied as a function of time- and dose
      dependent expression of the self antigen.

PMID- 8566041
TI  - C-C chemokines, but not the C-X-C chemokines interleukin-8 and interferon-gamma
      inducible protein-10, stimulate transendothelial chemotaxis of T lymphocytes.
AB  - Eight chemokines were tested for ability to elicit transendothelial chemotaxis of
      unstimulated peripheral blood T lymphocytes. The C-C chemokines monocyte
      chemotactic protein (MCP)-2, MCP-3, RANTES, macrophage inflammatory protein (MIP)
      1 alpha, MIP-1 beta, and, as previously described, MCP-1 induced significant,
      dose-dependent transendothelial chemotaxis of CD3+ T lymphocytes. In contrast,
      the C-X-C chemokines interleukin-8 (IL-8) and interferon-gamma inducible protein
      10 (IP-10) failed to induce transendothelial chemotaxis of CD3+ T lymphocytes or
      T lymphocyte subsets. RANTES, MIP-1 alpha, and MIP-1 beta induced significant
      transendothelial chemotaxis of CD4+, CD8+, and CD45R0+ T lymphocyte subsets.
      Phenotyping of mononuclear cells that underwent transendothelial migration to MCP
      2, MCP-3, RANTES, or MIP-1 alpha showed both monocytes and activated (CD26 high),
      memory-type (CD45R0+) T cells. Both CD4+ and CD8+ T lymphocytes were recruited,
      but not natural killer cells or significant numbers of B cells. MCP-2 was the
      only C-C chemokine tested that attracted a significant number of naive-type
      (CD45RA+) T lymphocytes. In the absence of endothelium, IL-8 but not IP-10
      promoted modest but significant chemotoxis of CD3+ T lymphocytes. Our data
      support the hypothesis that C-C, not the C-X-C chemokines IL-8 or IP-10, promote
      transendothelial chemotaxis of T lymphocytes.

PMID- 8566043
TI  - Identification of Sp1-binding sites in the CD11c (p150,95 alpha) and CD11a (LFA-1
      alpha) integrin subunit promoters and their involvement in the tissue-specific
      expression of CD11c.
AB  - The leukocyte integrins LFA-1 (CD11a/CD18) and p150,95 (CD11c/CD18) mediate cell
      cell and cell-extracellular matrix interactions during inflammatory responses and
      signal transduction into the cytoplasm. While the CD11a integrin subunit is
      expressed on all leukocytes, CD11c is almost exclusively expressed on cells of
      the myeloid lineage and on activated B lymphocytes. Its expression is regulated
      during cell activation and differentiation by transcriptional mechanisms. We have
      previously demonstrated that the proximal region of the CD11c promoter directs
      tissue-restricted and developmentally-regulated expression of reporter genes.
      Structural studies by electrophoretic mobility shift assays have demonstrated the
      presence of two Sp1-binding sites at -70 (Sp1-70) and -120 (Sp1-120) which
      mediate the Sp1 transactivation of the CD11c promoter in Sp1-defective SL2 cells,
      and which are involved in cell lineage-specific DNA-protein interactions, as
      demonstrated by footprinting in vivo. More importantly, mutation of either Sp1
      site inhibited the activity of the CD11c promoter both in myeloid U937 cells and
      the CD11c-expressing B lymphoblastoid JY cell line, while the opposite effect was
      observed in the CD11c-negative epithelial HeLa cell line, demonstrating the
      involvement of both Sp1-binding sites in the basal and the tissue-restricted
      expression of the CD11c integrin subunit gene. Interestingly, the analysis of the
      CD11a proximal promoter also revealed the existence of an Sp1-binding site at 
      70, indicating a common role for these cis-acting elements in the transcription
      of the leukocyte integrin alpha subunit genes. The binding of Sp1 to the
      regulatory regions of the leukocyte integrin genes raises the possibility that
      the retinoblastoma susceptibility gene product is implicated in integrin
      expression through its functional interaction with Sp1, thus establishing a link
      between integrin-dependent leukocyte adhesiveness and the state of cellular
      differentiation/proliferation.

PMID- 8566044
TI  - IgD class switching: identification of a novel recombination site in neoplastic
      and normal B cells.
AB  - IgD on normal B lymphocytes usually is co-expressed with IgM. A minority of
      normal plasma cells and rare B cell malignancies express exclusively IgD (IgM
      IgD+). The low frequency has been explained by the lack of a recognizable switch
      region within the C mu-C delta intron. We analyzed four cases of IgM-IgD+ hairy
      cell leukemia (HCL) by Southern (DNA) blot analysis and identified two cases with
      a recombinatorial event within the C mu-C delta intron and deletion of C mu. DNA
      sequence analysis of junctional regions showed that S mu or the immediate
      upstream region was used as a donor site and that the C mu-C delta intronic sigma
      delta region was used as acceptor site. Using polymerase chain reaction, we
      subsequently analyzed whether similar S mu-sigma delta recombinations occur in
      normal tonsils containing IgM-IgD+ plasma cells. Multiple products with a size
      range of 200-800 base pairs were detected in all four individuals, suggesting
      clustering of acceptor sites within sigma delta. Sequence analysis of three
      cloned products showed S mu-sigma delta recombinations similar those observed in
      HCL. The sigma delta region contains a relatively high content of pentameric
      repeats with an extremely G-rich area and appears to function as a vestigial
      switch recombination site in normal and neoplastic IgM-IgD+ B cells.

PMID- 8566046
TI  - Perforin dependence of natural killer cell-mediated tumor control in vivo.
AB  - Adaptive immune surveillance by T cells against infections and tumors depends on
      the presence of antigenic peptides presented by major histocompatibility complex
      (MHC) molecules. If antigenic tumor-specific peptides or MHC class I molecules
      are absent, the adaptive T cell immune response fails. Natural killer (NK) cells
      seem to complement the specific T cells by recognizing target cells lacking MHC
      class I (e.g. RMA-S). The role of perforin, which is crucially involved in T cell
      and NK cell-mediated target cell lysis, was evaluated in mice lacking perforin
      with respect to their capacity to eliminate a syngeneic lymphoid tumor. Here, we
      show that growth of MHC class I RMA-S tumor cells in unprimed mice was controlled
      by NK cells through perforin-dependent cytotoxicity.

PMID- 8566045
TI  - Regulation of Fas(Apo-1/CD95)- and perforin-mediated lytic pathways of primary
      cytotoxic T lymphocytes by the protooncogene bcl-2.
AB  - Cytotoxic T cells (CTL) induce cell death of their target cells either by the
      surface interaction between Fas ligand and Fas or by the release of perforin and
      granzymes. Both lytic pathways induce apoptosis yet it is not known whether
      identical or distinct apoptotic pathways are activated. The protooncogene bcl-2
      is known to protect various hematopoietic cells from apoptosis induced by diverse
      agents. Here we show that overexpression of the Bcl-2 protein in the murine
      mastocytoma line P815 or in concanavalin A-activated splenocytes suppresses
      apoptotic cell death induced by allospecific primary cytotoxic T lymphocytes
      (CTL) in which only the Fas lytic pathway was functional. Bcl-2 also reduced
      target cell killing induced by CTL whose lytic activity was dependent on the
      perforin/granzyme pathway only. These data provide evidence that, in the target
      cells studied here, both perforin/granzyme and Fas apoptotic pathways are
      modulated by Bcl-2 and suggest that these two pathways converge at a step prior
      to Bcl-2 inhibition.

PMID- 8566047
TI  - Default development of cloned human naive CD4 T cells into interleukin-4- and
      interleukin-5- producing effector cells.
AB  - It was recently demonstrated that naive human and mouse CD4 T cells release low
      but sufficient levels of interleukin (IL)-4 at priming to support their
      development into IL-4 producers. To determine whether this IL-4 is produced by a
      minor subset of cells, freshly isolated human naive CD4 T cells were directly
      cloned by limiting dilution in the absence of exogenous IL-4. More than 95% of
      neonatal and 60% of adult naive T cells seeded in single-cell cultures could be
      expanded upon stimulation with anti-CD3 mAb immobilized on CD32-B7.1 L cell
      transfectants in the presence of IL-2. All 171 clones derived from four neonates
      and two adults produced IL-4 and IL-5 at generally high levels. Like the allergen
      specific human Th2 clones described in the literature, these T cell clones
      produced little or no interferon-gamma upon stimulation via their T cell
      receptor/CD3 complex, whereas they released high levels of this cytokine when
      activated with phorbol 12-myristate 13-acetate+ionomycin. Cells cloned and
      expanded in the presence of anti-IL4 + anti-IL-4R mAb produced much lower levels
      of IL-4 and IL-5. It is concluded that almost every single naive human CD4 T cell
      primed and expanded in the absence of exogenous IL-4 releases sufficient
      autocrine IL-4 to support its clonal expansion into high IL-4/IL-5 producers.

PMID- 8566048
TI  - Transdermal immunization with large proteins by means of ultradeformable drug
      carriers.
AB  - By means of novel, ultradeformable and self-optimizing agent carriers called
      transfersomes, large molecules can be brought into the body through intact
      permeability barriers. This permits non-invasive immunization through normal skin
      and gives rise to a similar or even slightly higher antibody titer than
      subcutaneous injections of the same immunogen formulation. The former type of
      immunization also results in a higher IgA/IgG ratio in the blood than the
      repeated immunogen injections, as shown here for a soluble protein, human serum
      albumin, as well as for an integral membrane protein, gap junction protein, in
      mice.

PMID- 8566049
TI  - Antibody-targeted superantigen therapy induces tumor-infiltrating lymphocytes,
      excessive cytokine production, and apoptosis in human colon carcinoma.
AB  - Bacterial superantigens are the most potent known activators of human T
      lymphocytes. To engineer superantigens for immunotherapy of human colon
      carcinoma, the superantigen, staphylococcal enterotoxin A (SEA) was genetically
      fused to the Fab region of the colon carcinoma-reactive monoclonal antibody C242.
      In the present study the effector mechanisms involved in the anti-tumor response
      to C242 Fab-SEA were characterized. Immunohistochemistry and computer-aided image
      analysis were used in studies of cryopreserved tumor tissue to evaluate the
      phenotype of infiltrating cells and their cytokine profiles in response to
      therapy. Human T cells and monocytes were recruited to the tumor area and
      penetrated the entire tumor mass within hours after injection of C242 Fab-SEA.
      The production of cytokines at the single-cell level was found to be dominated by
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12,
      interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor, and
      transforming growth factor-beta, whereas IL-1-alpha, IL-1ra, IL-1 beta, TNF-beta,
      IL-3, IL-6, and IL-8 were undetectable. Most of the TNF-alpha, IL-2, IL-12, and
      IFN-gamma were made by the infiltrating human leukocytes, while the colon
      carcinoma cells were induced to produce IL-4, IL-10, and TNF-alpha. Up-regulation
      of IFN-gamma receptors and TNF R p60 receptors was found, while the TNF R p80
      receptor was absent. The cytokine production, T cell infiltration, and CD95 Fas
      receptor expression concomitantly occurred to induce programmed cell death in the
      tumor cells. This was followed by a strong reduction of the tumor mass that was
      seen within 24 h after C242 Fab-SEA infusion. These findings demonstrate that
      antibody-superantigen proteins efficiently recruit tumor-infiltrating lymphocytes
      actively producing a variety of cytokines likely to be essential for the
      therapeutic effects observed in the model. Although the humanized SCID model has
      obvious limitations in its predictive value for treatment of human cancer, we
      believe that these results encourage clinical evaluation of antibody-targeted
      superantigens.

PMID- 8566050
TI  - Characterization of thymic stromal-derived lymphopoietin (TSLP) in murine B cell
      development in vitro.
AB  - B cell development is dependent on both direct interactions with stromal cells
      and their secreted cytokines. The precise mechanisms by which these interactions
      regulate B cell differentiation are currently unknown. We report here that a
      novel growth factor thymic stromal-derived lymphopoietin (TSLP) can replace the
      activity of interleukin-7 (IL-7) in supporting B cell development in vitro. TSLP
      was found to promote the proliferation and differentiation of committed B220+ B
      cell progenitors from day 15 fetal liver. Phenotypic analysis of these cells
      revealed that they are at the pro-B cell stage of differentiation and express
      cell surface markers characteristic of pro-B cells cultured in IL-7. TSLP can
      replace the activity of IL-7 in supporting the progression of B lymphocytes from
      uncommitted bipotential precursors. In the absence of either TSLP or IL-7, the
      progeny of cells that give rise to mature B lymphocytes fail to develop from
      these bipotential precursors. Moreover, TSLP can substitute for IL-7 in
      supporting the sustained proliferative response exhibited by B cell progenitors
      from CBA/N mice. Together these results show that TSLP can replace the
      requirement for IL-7 during in vitro B cell development.

PMID- 8566051
TI  - Characterization of cytokine production in murine Trypanosoma cruzi infection by
      in situ immunocytochemistry: lack of association between susceptibility and type
      2 cytokine production.
AB  - Cytokine production in the spleens of mice infected with the protozoan parasite
      Trypanosoma cruzi was analyzed in three models which differ in the outcome of the
      infection. Using immunocytochemical techniques to detect cytokine-producing
      cells, the production of type 1 [interleukin-2 (IL-2) and interferon (IFN)
      gamma], type 2 (IL-4, IL-5, IL-10), inflammatory [tumor necrosis factor (TNF)
      alpha, IL-1 alpha, IL-6] and regulatory (transforming growth factor-beta)
      cytokines were examined. With the exception of IL-4 and IL-5, cells producing all
      of the cytokines assayed were detected in both the resistant and susceptible
      models of T. cruzi infection. Cells producing IL-4 and IL-5 were not detected
      until later in infection in the resistant mice (> 34 days), at about the time
      animals of the susceptible strain succumb to the infection. Mice of the
      susceptible model showed a slight delay in the appearance of cells producing the
      type 1 cytokines IL-2 and IFN-gamma and an earlier appearance of TNF-producing
      cells, in comparison to resistant mice. Cells producing IL-2 or IL-10 were
      transient in their appearance in the spleen while cells producing IL-1, IL-4, IL
      5, IL-6, IFN-gamma, TNF, or TGF-beta were first detectable in either the acute or
      post-acute stage of the infection and persisted up to 700 days post infection in
      two different resistant models of the infection. Cells producing IFN-gamma, TNF
      alpha and TGF-beta were particularly numerous even very late in the infection.
      Double-staining techniques were used to show that the vast majority of the IFN
      gamma-producing cells in the spleen were CD4-, CD8- alpha/beta TCR+T cells. This
      study confirms the transience of IL-2 production in the acute stage of T. cruzi
      infection and the persistent and simultaneous production of type 1 and type 2
      cytokines during the late-acute and chronic stages of the infection.
      Susceptibility or resistance to T. cruzi infection does not associate with a Th2
      pattern of cytokine production in the three models examined in this study. The
      overlapping pattern of type 1 and type 2 cytokine-producing cells in both the
      acute and chronic stages of T. cruzi infection demonstrates that longterm
      infections do not necessarily lead to a dominance of either type 1 or type 2
      cytokine production.

PMID- 8566052
TI  - Expression of gp40, the murine homologue of human epithelial cell adhesion
      molecule (Ep-CAM), by murine dendritic cells.
AB  - Dendritic cells (DC) can be distinguished from other antigen-presenting cells
      (APC) by their morphology, motility and ability to initiate primary responses in
      naive T cells. Certain cell surface proteins (e.g. major histocompatibility
      complex antigens, co-stimulatory/adhesion molecules and DEC205) are selectively
      expressed by DC, and may contribute to the potent APC activity of these
      leukocytes. As an outgrowth of studies of adhesion molecules expressed by
      epithelia and Langerhans cells (LC), we examined DC from murine epidermis and
      various lymphoid tissues for evidence of expression of gp40, a glycoprotein
      recently identified as the murine homologue of human epithelial cell adhesion
      molecule (Ep-CAM). gp40 was detected on freshly-obtained LC, cultured LC and LC
      that migrated from skin explants, as well as on keratinocytes. In skin-associated
      lymph nodes, gp40 was selectively expressed by some DC in T cell-dependent areas.
      DC-enriched preparations from skin-associated lymph nodes and spleen contained
      many cells that co-expressed DC markers (CD11c and DEC205) and high levels of
      gp40. Lower levels of gp40 were present on DC from gut-associated lymph nodes.
      These results demonstrate that the putative homophilic adhesion molecule gp40 is
      expressed by subpopulations of DC in selected tissues; we propose that gp40
      expression may have functional consequences for DC.

PMID- 8566053
TI  - Inhibition of resistance to hemopoietic allo-grafts in granulocyte colony
      stimulating factor transgenic mice.
AB  - Transplanted allogeneic marrow cells often fail to engraft in a lethally
      irradiated host. This phenomenon, termed resistance to allogeneic marrow grafts
      or alloresistance, is well documented, although its mechanism is not yet
      understood. Transplantation of major histocompatibility complex disparate
      allogeneic marrow cells into mice transgenic for granulocyte colony-stimulating
      factor (G-CSF) showed donor-derived spleen colonies (CFU-S) and resulted in
      stable allogeneic chimerism with excellent survival (100% up to 40 days and 89%
      up to 120 days). Under the same experimental conditions, all the littermate
      controls failed to show CFU-S and died shortly after marrow transplantation.
      Thus, resistance to allogeneic marrow cells appeared to be severely impaired in
      this transgenic mouse. The observation that neutralizing antibody against G-CSF
      restored allo-resistance in G-CSF transgenic mice and that CFU-S was inducible
      upon administration of recombinant G-CSF using a mini-osmotic pump in
      nontransgenic recipients, suggests that an elevated level of this cytokine is
      important for the inhibition of allo-resistance. Thus, G-CSF was found to play a
      role in allogeneic resistance to marrow grafts and the G-CSF-transgenic mice
      provide a useful model to study the inhibition of the resistance. The inhibition
      of allo-resistance may be useful in preparing allogeneic bone marrow chimeras in
      both experimental and clinical settings.

PMID- 8566054
TI  - Tepoxalin blocks neutrophil migration into cutaneous inflammatory sites by
      inhibiting Mac-1 and E-selectin expression.
AB  - Inflammation is characterized by the migration of polymorphonuclear leukocytes
      from the vasculature into the tissue causing profound injury. Adhesion and
      migration of neutrophils across the vascular bed are governed by a series of
      complex events including cytokine/chemokine production which in turn orchestrates
      the temporal expression of a cohort of adhesion molecules mediating the
      migration. Many of these adhesion molecules and their inducers are under the
      control of inflammatory response transcriptional factors such as NF kappa B and
      AP-1. Recently we showed tepoxalin, previously known as a dual
      cyclooxygenase/lipoxygenase (CO/LO) inhibitor, to be a potent inhibitor of NF
      kappa B-induced transcription in vitro. In this study, we demonstrated that when
      administered in vivo, tepoxalin but not naproxen (a nonsteroidal anti
      inflammatory drug, NSAID) or zileuton (an LO inhibitor), effectively inhibits
      neutrophil migration into inflammatory sites in murine skin stimulated by either
      lipopolysaccharide (LPS) or tumor necrosis factor-alpha. Immunohistochemical
      analysis indicates that 10-50 mg/kg of tepoxalin inhibits neutrophil migration.
      It also effectively blocks the upregulation of Mac-1 (CD11b/CD18) on neutrophils.
      Quantitative polymerase chain reaction Mac-1 analysis shows that LPS-induced
      transcription of E-selectin mRNA was dramatically suppressed by both 25 and 50
      mg/kg of tepoxalin, whereas the level of ICAM-1 was only affected by 50 mg/kg of
      tepoxalin. Since it has been documented that the expression of E-selectin and Mac
      1 is regulated either directly or indirectly by the transcription factor NF kappa
      B, our studies provide in vivo evidence that tepoxalin is a potent inhibitor of
      NF kappa B-mediated events in animal models and this novel molecular mechanism
      clearly defines it as a new class of anti-inflammatory compounds.

PMID- 8566055
TI  - Peripheral tolerance in T cell receptor-transgenic mice: evidence for T cell
      anergy.
AB  - T cell tolerance can be induced in adult mice by injection of soluble antigenic
      peptide. The underlying mechanism has been difficult to establish in normal mice
      due to the low precursor frequency of T cells specific for any given antigen.
      Therefore, we examined peripheral tolerance in mice transgenic for a T cell
      receptor specific for a cytochrome c peptide bound to I-Ek. Antigen-specific
      hyporesponsiveness could be induced in the transgenic mice. We followed the
      transgene-bearing T cells with a clonotypic monoclonal antibody and found similar
      numbers of clonotypic T cells in tolerized and control mice. To prevent de novo
      differentiation of T cells we analyzed thymectomized mice in which antigen
      specific hyporesponsiveness was induced. Our analysis of thymectomized transgenic
      mice showed that antigen-specific T cell hyporesponsiveness following injection
      of peptide intravenously is not caused by gross elimination of T cells. These
      data provide evidence for the role of anergy in peripheral tolerance.

PMID- 8566056
TI  - Autoreactive T cell specificity in autoimmune hemolytic anemia of the NZB mouse.
AB  - Splenic T cells from Coombs'-positive New Zealand Black (NZB) mice proliferated
      consistently in vitro in response to the integral red blood cell (RBC) membrane
      protein Band 3, the antigen previously shown to be the target for the pathogenic
      RBC autoantibodies. The responding cells predominantly express CD4 and the
      proliferative response is blocked by antibodies to the NZB major
      histocompatibility complex class II but not by antibodies to an irrelevant H-2
      haplotype. NZB splenic T cells also proliferated in response to the internal
      membrane skeleton protein spectrin. By contrast, T cells from BALB/c and DBA2
      mice, which bear the same H-2 haplotype as NZB mice, but which do not develop
      autoimmune hemolytic anemia (AIHA), fail to respond to Band 3. It is considered
      that these results support the hypothesis that Band 3-reactive T cells provide
      help for the production of pathogenic anti-Band 3 autoantibodies in NZB mice. T
      cells from Coombs'-negative NZB mice as young as 3 weeks old proliferated in
      response to Band 3; moreover, the RBC from Coombs'-negative mice bore elevated
      levels of autoantibody as judged by a sensitive direct enzyme-linked anti
      globulin test. Thus, the pathology of AIHA develops at a much earlier age than
      was thought previously.

PMID- 8566057
TI  - Tissue-specific deoxyribonuclease I-hypersensitive sites in the vicinity of the
      immunoglobulin C lambda cluster of man.
AB  - During B cell development, the onset of DNA rearrangements, expression, and
      somatic hypermutation of Ig genes are regulated through the complex interaction
      of cis-acting elements with trans-acting factors. Our aim is to identify DNA
      elements required during activation of the human Ig lambda light chain genes.
      Determination of deoxyribonuclease (DNase) I-hypersensitive sites in complex
      regulated genes can lead to the identification of sequence elements which would
      have been overlooked by employing transient transfection protocols. We have
      therefore investigated the chromatin structure of human J-C lambda genes and
      identified three DNase I-hypersensitive sites (HSS-1, -2, and -3) within an 8-kb
      region downstream of the J-C lambda 7 gene. HSS-2 and HSS-3 are B cell specific.
      The DNase I-hypersensitive sites are also present in kappa-producing cell lines
      which have not rearranged the Ig lambda locus and produce germ-line J-C lambda
      transcripts. We conclude that in mature B cells, both kappa and lambda loci are
      in an active structure regardless of the type of light chain they produce. This
      suggests that the chromatin structure of both loci is opened early in B cell
      development and that the active structure persists in mature B cells. The
      observed temporal order (first kappa, then lambda) of activation can be explained
      by consecutive synthesis of the appropriate regulating factors and the tight
      regulation of the recombination machinery through the products of L chain gene
      rearrangements.

PMID- 8566058
TI  - Major histocompatibility complex genes determine natural killer cell tolerance.
AB  - Murine natural killer (NK) cell subsets, as defined by expression of members of
      the Ly49 gene family, discriminate target cells expressing different major
      histocompatibility complex (MHC) class I alleles. For example, Ly49A+ NK cells
      lyse H-2b but not H-2d tumor target cells. The specificity arises because Dd on
      target cells binds to Ly49A, transducing an inhibitory signal into the Ly49A+ NK
      cells. The capacity of NK cells to discriminate allelic class I determinants
      raises a key issue: are NK cells self-tolerant, and if so what are the mechanisms
      that lead to self-tolerance? As previously reported, potentially autoaggressive
      Ly49A+ NK cells are not clonally deleted in H-2b mice. However, IL-2-cultured
      Ly49A+ effector cells from H-2b mice exhibit reduced lysis of H-2b (self)
      concanavalin A blast target cells, compared to Ly49A+ effector cells from H-2d
      mice. Possible mechanisms accounting for this self-tolerance are addressed in
      this report. Self-tolerance was not due to anergy of the cells, because the
      Ly49A+ effector cells from both types of mice lysed beta 2-microglobulin
      deficient target cells efficiently and equivalently. These results also suggest
      that tolerance results from inhibition mediated by beta 2m-dependent H-2b class I
      molecules. Significantly, blockade of Ly49A on Ly49A+ effector cells from H-2b
      mice did not restore lysis of H-2b target cells, suggesting that inhibition is
      not mediated through the Ly49A receptor. Additional experiments suggest that
      inhibition is also not mediated primarily through the Ly49C receptor. These
      results suggest that Ly49A+ effector cells from H-2b mice, unlike those from H-2d
      mice, express inhibitory receptors specific for H-2b molecules that are distinct
      from Ly49A and Ly49C.

PMID- 8566059
TI  - Expression of the common cytokine receptor gamma chain by murine dendritic cells
      including epidermal Langerhans cells.
AB  - The common cytokine receptor gamma chain (gamma c) is an indispensable component
      of interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15 receptors, and its expression
      has been detected in several leukocyte populations, including T cells, B cells,
      monocytes, natural killer cells, and neutrophils. The purpose of this study was
      to determine whether gamma c receptors are expressed by dendritic cells (DC).
      Constitutive gamma c mRNA expression was observed by reverse transcription
      polymerase chain reaction and/or Northern blotting for: (a) Ia+ epidermal
      Langerhans cells (LC), (b) 4F7+ splenic DC, (c) granulocyte/macrophage colony
      stimulated factor-propagated bone marrow-derived DC, and (d) the epidermal
      derived DC line, XS52, which retains important functions of epidermal LC.
      Exposure of XS52 cells to recombinant IL-4 induced a rapid up-regulation of c-myc
      mRNA expression, and this IL-4-dependent signaling was blocked almost completely
      by anti-gamma c monoclonal antibody (mAb) TUGm2 in a soluble form. Moreover, c
      myc up-regulation was inducible in XS52 cells by the same mAb in an immobilized
      form. These results imply that molecules recognized by this antibody (i.e. gamma
      c receptors) are expressed on XS52 cell surfaces. We thus conclude that DC
      express functional gamma c receptors, which then mediate cytokine-dependent
      regulation of DC functions.

PMID- 8566060
TI  - Disease in the scurfy (sf) mouse is associated with overexpression of cytokine
      genes.
AB  - The murine X-linked lymphoproliferative disease scurfy is similar to the Wiskott
      Aldrich syndrome in humans. Disease in scurfy (sf) mice is mediated by CD4+ T
      cells. Based on similarities in scurfy mice and transgenic mice that overexpress
      specific cytokine genes, we evaluated the expression of cytokines in the lesions
      of sf mice by Northern blotting, quantitative reverse-transcription polymerase
      chain reaction (RT-PCR) and by hybridization in situ. Overall, the phenotypic
      characteristics of scurfy disease correlated well with increased interleukin (IL)
      4 (lymphadenopathy), IL-6 (B cell proliferation, hypergammaglobulinemia), IL-7
      (dermal inflammatory cell infiltration), and high levels of tumor necrosis factor
      alpha (wasting).

PMID- 8566061
TI  - Interleukin-10 inhibits cytokine generation from mast cells.
AB  - This report examines the effects of recombinant murine interleukin-10 (rmIL-10)
      on antigen-induced beta-hexosaminidase, leukotriene (LT)C4 and cytokine release
      from mouse bone marrow-derived mast cells (BMMC). BMMC sensitized to hapten
      monoclonal IgE directed against dinitrophenol-bovine serum albumin (DNP-BSA) and
      challenged with 10 ng/ml DNP-BSA generated beta-hexosaminidase and LTC4-like
      material which was followed by tumor necrosis factor-alpha (TNF-alpha) and
      granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA expression and
      protein release. Incubation of BMMC with 1-100 ng/ml rmIL-10 inhibited cytokine
      generation, without affecting beta-hexosaminidase and LTC4-like material release.
      TNF-alpha, but not GM-CSF mRNA expression, was also diminished in rmIL-10-treated
      BMMC, suggesting that down-regulation of cytokine production by rmIL-10 involves
      different mechanisms. These results identify a novel biological action of IL-10
      as an inhibitor of cytokine production by stimulated mast cells.

PMID- 8566062
TI  - In vitro cultured stromal cells from human tonsils display a distinct phenotype
      and induce B cell adhesion and proliferation.
AB  - Peripheral lymphoid tissues contain a fibroblastic cell type referred to as
      stromal cells or reticulum cells which interact with lymphocytes as part of the
      lymphoid microenvironment. After isolation from human tonsils and expansion in
      vitro we analyzed the surface phenotype, extracellular matrix components,
      cytoskeletal products, cytokine production, binding and functional interaction
      with B lymphocytes of in vitro cultured stromal cells (HTSC) both in resting
      condition and after activation with tumor necrosis factor (TNF)-alpha and
      interferon (IFN)-gamma. Our results show that HTSC do not express specific
      myeloid, lymphoid, endothelial or epithelial markers. HTSC express CD54 (ICAM-1),
      CD49a (VLA-1), CD49b (VLA-2), CD49c (VLA-3), CD49e (VLA-5), CD49f (VLA-6), CD29,
      CD51, CD44 and produce vinculin, beta-tubulin, alpha-actin, vimentin,
      fibronectin, laminin and collagen types I, III and IV. Activation of HTSC up
      regulated CD54 (ICAM-1) and induced HLA-DR and CD106 (VCAM-1). HTSC
      constitutively produce interleukin (IL)-6 which is enhanced upon activation with
      TNF-alpha. IL-8 and granulocyte/macrophage colony-stimulating factor are detected
      only in the supernatants of activated HTSC. Reverse transcriptase polymerase
      chain reaction analysis revealed that HTSC display mRNA for IL-1 alpha, leukemia
      inhibitory factor and IL-7. The adhesion of tonsillar B lymphocytes to activated
      HTSC is mediated by CD11a/CD18 and CD54. Furthermore, HTSC can induce maximal
      proliferation of IL-2-activated B lymphocytes cocultured in direct cell-cell
      contact with HTSC. These results clearly distinguish in vitro cultured HTSC from
      common fibroblasts and other non-lymphoid elements present in the lymphoid
      parenchyma, such as follicular dendritic cells, and show that HTSC actively
      participate in the lymphoid microenvironment. In vitro cultures of HTSC could
      therefore be a useful model system for detailed analysis of the interactions
      between stromal cells and lymphocytes under physiological and pathological
      conditions.

PMID- 8566063
TI  - Nerve growth-factor and anti-CD40 provide opposite signals for the production of
      IgE in interleukin-4-treated lymphocytes.
AB  - Nerve growth factor (NGF) is a well-known neurotrophic factor acting on both the
      peripheral and the central nervous systems. In addition, it has been shown to
      play a role in the function of the immune system through specific receptors. Both
      high-affinity and low-affinity NGF receptors (NGFR) are expressed on human B
      lymphocytes. The low-affinity NGFR has been shown to have structural homology
      with another specific B cell surface molecule, CD40, which plays an important
      role in IgE production. In view of the structural similarities of the p75 NGFR
      and CD40 we examined whether NGF may also be involved in the regulation of IgE
      production. We found that NGF and anti-CD40 exerted opposite effects on the
      induction of IgE by IL-4 in peripheral blood mononuclear cells. NGF inhibited the
      induction of IgE by IL-4 and this inhibition was not mediated through blocking of
      the induction of CD23 nor through inhibition of IL-4R expression. The inhibition
      of IL-4-dependent IgE production was observed on surface (s)IgE+ and sIgE-/sIgM+
      B lymphocytes. Anti-CD40 on the other hand, exerted an enhancing effect on IgE
      production and its addition to IL-4 provided a signal that was resistant to the
      inhibitory effect of NGF. Antagonistic effects of NGF and IL-4 were also observed
      for other Ig isotypes since IL-4 prevented the increase in IgA and IgM production
      induced by NGF. These data indicate that although NGFR and CD40 belong to the
      same receptor superfamily and exert similar proliferative effects on B
      lymphocytes, they interact differently with IL-4 in the regulation of IgE
      production.

PMID- 8566064
TI  - Analysis of major histocompatibility complex class I-restricted hapten
      recognition by mutation of the V-J joining of T cell receptor alpha chains.
AB  - Hapten-specific T cell responses are responsible for chemically induced immune
      disorders. However, the molecular details of hapten interactions with T cell
      receptors (TCR) are poorly understood. Recent studies of trinitrophenyl (TNP)
      specific responses revealed major histocompatibility complex-associated TNP
      peptides as dominant epitopes for CD8+ and CD4+ T cells. The present study is
      based on the observation that two H-2Kb/TNP-specific CTL clones (II/7 and III/1),
      differing exclusively in two amino acids of their TCR alpha chains, also differed
      in their carrier specificities for various TNP-peptides. The genes of the two
      alpha chains and the common beta chain were cloned into expression vectors.
      Transfection of the TCR alpha chain of clone III/1 into a hybridoma of clone II/7
      also transferred the fine specificity of clone III/1, indicating that the small
      alpha chain variations were indeed responsible for the different carrier
      specificities. Point mutations bridging the difference between the alpha chains
      of clones II/7 and III/1 and functional studies of the respective TCR alpha beta
      transfectants into a TCR-negative hybridoma revealed an unexpected result: the
      two receptors did not represent examples of structural complementarity for
      different sets of hapten-peptide conjugates; rather, they resembled two
      structures of principally similar specificity but of significantly different
      overall affinity. This was demonstrated more directly by comparing the fine
      specificities of III/1 transfectants expressing or not expressing the co-receptor
      CD8: the CD8-negative III/1 transfectant assumed a specificity pattern
      indistinguishable from that of a CD8-expressing, II/7-derived transfectant.
      Hence, comparable alterations of antigen recognition may be induced either by
      subtle TCR alterations or by removal of CD8, i.e. by the presence or absence of a
      non-polymorphic adhesion molecule.

PMID- 8566065
TI  - High doses of interleukin-12 inhibit the development of joint disease in DBA/1
      mice immunized with type II collagen in complete Freund's adjuvant.
AB  - Collagen-induced arthritis (CIA) is an (autoimmune) joint disease readily
      elicited in DBA/1 mice by immunization with type II collagen (CII) emulsified
      with complete Freund's adjuvant. It is a destructive arthritis involving about
      50% of the limbs and occurs with an incidence of 70% to 100%. In this study we
      evaluated the effect of mouse recombinant interleukin-12 (mrIL-12) on CIA.
      Administration of mrIL-12 at high doses (1 micrograms/mouse, daily) for 2 or 3
      weeks delayed the onset and reduced the incidence of CIA. Furthermore, the
      severity of CIA was much milder and in most cases restricted to single digits of
      the paws. Short-term administration of high doses of IL-12 exerted some, but less
      pronounced, disease-suppressing effect. In contrast, 10-fold lower doses of IL-12
      given during the first 3 weeks, or high doses of IL-12 administered
      therapeutically proved to be ineffective. Only those regimens of IL-12 treatment
      that ameliorated CIA were associated with a down-regulation of the CII-specific
      antibody response. A strong inhibition of CII-specific IgG1 antibodies (10- to 20
      fold) and a moderately (2- to 6-fold) suppressed IgG2b response was observed,
      whereas the level of CII-specific IgG2a antibodies remained high. Taken together,
      the results indicate that some initial events in the induction of CIA in DBA/1
      mice injected with CII emulsified with CFA are suppressed by treatment with high
      doses of IL-12.

PMID- 8566066
TI  - B cell-B cell interaction through intercellular adhesion molecule-1 and
      lymphocyte functional antigen-1 regulates immunoglobulin E synthesis by B cells
      stimulated with interleukin-4 and anti-CD40 antibody.
AB  - IgE synthesis by purified human B cells is induced by two signals: a class
      switching factor, most commonly interleukin (IL)-4, and the engagement of CD40,
      which is activated through its interaction with CD40 ligand (CD40L) expressed on
      activated T cells. Thus, the combination of IL-4 and anti-CD40 monoclonal
      antibody (mAb) has been shown to stimulate IgE production in vitro by highly
      purified B cells. In this T cell-independent system, strong homotypic aggregation
      of B cells is observed prior to the production of IgE. Flow cytometric analysis
      and cell binding assays showed that the stimulation of purified B cells with anti
      CD40 mAb plus IL-4 resulted in a striking increase of intercellular adhesion
      molecule (ICAM)-1(CD54) expression, an induction of CD43 and an avidity change of
      lymphocyte functional antigen (LFA)-1(CD11a/CD18), with little augmentation of
      CD18 expression. Addition of anti-ICAM-1 mAb caused an inhibition of homotypic
      aggregation but augmented IgE synthesis by B cells stimulated with anti-CD40 mAb
      and IL-4, although it did not affect B cell proliferation or IL-6 production by
      the B cells. Among the mAb against counter-receptors for ICAM-1 tested, anti
      CD11a mAb suppressed IgE synthesis, while anti-CD18 mAb and anti-CD43 mAb had
      little effect. The enhancing or inhibitory effect of anti-ICAM-1 mAb or anti
      CD11a mAb on IgE production was achieved by the increased or decreased expression
      of germline C epsilon transcripts by B cells stimulated with anti-CD40 mAb and IL
      4. These results indicate that B cell-B cell interaction through ICAM-1 and one
      of its counter receptors, LFA-1, regulates IgE synthesis by modulating C epsilon
      germ-line transcription.

PMID- 8566067
TI  - Lack of intermediate-affinity interleukin-2 receptor in mice leads to dependence
      on interleukin-2 receptor alpha, beta and gamma chain expression for T cell
      growth.
AB  - An interleukin (IL)-4 dependent mouse T cell clone 8.2 derived from an IL-2
      dependent T cell line was characterized. As measured by flow cytometric analysis
      and Northern blotting, it expresses IL-2 receptor beta (IL-2R beta) and gamma (IL
      2R gamma) chains, but has lost expression of IL-2 receptor alpha chain (IL-2R
      alpha). To investigate the properties of the mouse IL-2R beta gamma complex and
      the role of IL-2R alpha gene expression, this clone was further studied. T cell
      clone 8.2 has lost the capacity to bind 125I-labeled human IL-2 under
      experimental conditions able to detect intermediate-affinity IL-2R in human
      cells. Mouse IL-2 is unable to block the binding of mAb TM beta 1 to 8.2 cells.
      Under the same experimental conditions, mouse IL-2 blocks the binding of TM beta
      1 to C30-1 cells expressing the IL-2 alpha beta gamma complex. Since TM beta 1
      recognizes an epitope related to the IL-2 binding site of IL-2R beta, these
      results can be taken as a demonstration that mouse IL-2R beta gamma does not bind
      mouse IL-2. Furthermore, T cell clone 8.2 does not proliferate in response to
      recombinant mouse or human IL-2. On the other hand, T cell transfectant lines
      expressing heterospecific receptors made of the human IL-2R beta and mouse IL-2R
      gamma chains bind 125I-labeled human IL-2 and proliferate in response to IL-2.
      This establishes the difference between mouse and human IL-2R beta chains.
      Transfection of T cell clone 8.2 with human IL-2R alpha genes restores their
      capacity to proliferate in response to IL-2. In addition, all transfectants grown
      in IL-2 express the endogeneous mouse IL-2R alpha chain. When grown in IL-4, the
      endogeneous mouse IL-2R alpha gene remains silent in all these transfectants.
      These results show that, contrary to the human, the mouse does not express an
      intermediate-affinity IL-2R. Expression of the IL-2R alpha gene is therefore
      required for the formation of the functional IL-2R in mice.

PMID- 8566068
TI  - The beta 2 integrin Mac-1 but not p150,95 associates with Fc gamma RIIA.
AB  - In this study we have compared the ligand binding activity of the two closely
      related beta 2 integrins, Mac-1 and p150,95, which are expressed separately as
      receptors permanently transfected into K562 cells. Mac-1 has previously been
      shown to associate with Fc gamma R, particularly Fc gamma RIII, but K562 cells
      express only endogenous Fc gamma RIIA. We have, therefore, taken advantage of
      this situation to examine a possible relationship between Fc gamma RIIA with Mac
      1 and p150,95 in the absence of other Fc gamma R. The main finding is that anti
      Fc gamma RII mAb have a profound inhibitory effect on cell adhesion mediated by
      Mac-1, but not on the adhesion mediated by p150,95. Thus, in spite of the fact
      that Mac-1 and p150,95 bind to the same or at least a very similar selection of
      ligands, their association with other receptors on the cellular membrane, and
      therefore their mode of regulation may be different.

PMID- 8566069
TI  - CD4-negative cytotoxic T cells with a T cell receptor alpha/beta intermediate
      expression in CD8-deficient mice.
AB  - Targeted disruption of the CD8 gene results in a profound block in cytotoxic T
      cell (CTL) development. Since CTL are major histocompatibility complex (MHC)
      class I restricted, we addressed the question of whether CD8-/- mice can reject
      MHC class I-disparate allografts. Studies have previously shown that skin
      allografts are rejected exclusively by T cells. We therefore used the skin
      allograft model to answer our question and grafted CD8-/- mice with skins from
      allogeneic mice deficient in MHC class II or in MHC class I (MHC-I or MHC-II
      disparate, respectively). CD8-/- mice rejected MHC-I-disparate skin rapidly even
      if they were depleted of CD4+ cells in vivo (and were thus deficient in CD4+ and
      CD8+ T cells). By contrast, CD8+/+ controls depleted of CD4+ and CD8+ T cells in
      vivo accepted the MHC-I-disparate skin. Following MHC-I, but not MHC-II
      stimulation, allograft-specific cytotoxic activity was detected in CD8-/- mice
      even after CD4 depletion. A population expanded in both the lymph nodes and the
      thymus of grafted CD8-/- animals which displayed a CD4-8-3intermediateTCR
      alpha/betaintermediate phenotype. Indeed its T cell receptor (TCR) density was
      lower than that of CD4+ cells in CD8-/- mice or of CD8+ cells in CD8+/+ mice. Our
      data suggest that this CD4-8- T cell population is responsible for the CTL
      function we have observed. Therefore, MHC class I-restricted CTL can be generated
      in CD8-/- mice following priming with MHC class I antigens in vivo. The data also
      suggest that CD8 is needed to up-regulate TCR density during thymic maturation.
      Thus, although CD8 plays a major role in the generation of CTL, it is not
      absolutely required.

PMID- 8566070
TI  - Inhibition of murine B1 lymphocytes by interleukin-12.
AB  - B1 cells are a subset of B lymphocytes found in many species and are implicated
      in the development of autoimmunity. B1 cells have previously been shown to be
      suppressed by the T helper (Th)1 cytokine interferon (IFN)-gamma, and to be
      stimulated by the Th2 cytokines interleukin (IL)-2, IL-4, IL-5 and IL-10. To
      examine further the interactions of B1 cells and Th1 cells, we have now tested
      the effects of the Th1 cell-inducing cytokine IL-12 on murine B1 cells. BALB/c
      mice were immunized with phosphorylcholine conjugated to keyhole limpet
      hemocyanin (PC-KLH) and simultaneously treated with 1 microgram recombinant
      murine IL-12 for 3 consecutive days. In addition to altering the isotype and
      idiotype distribution of anti-PC antibodies, IL-12 treatment was found to cause a
      loss of peritoneal, but not splenic B lymphocytes in immunized mice. B cell
      depletion required exposure to IL-12 plus antigenic stimulation. Levels of
      peritoneal B lymphocytes were fully restored by day 45, but the majority of these
      cells belonged to the B2 subset. Additionally, proliferation of B1 cells in vitro
      induced by IL-5 was substantially inhibited by IL-12. IL-12 itself had no effect
      on viable cell recovery of peritoneal cells (PeC) cultured in vitro, but viable
      cell recovery was significantly decreased in PeC cultured with IL-5 plus IL-12.
      These results show that IL-12 causes the loss of murine peritoneal B1 cells and
      suggest that treatment with this cytokine may be useful for disease conditions
      that involve B1 cell dysfunction.

PMID- 8566071
TI  - A tyrosinase nonapeptide presented by HLA-B44 is recognized on a human melanoma
      by autologous cytolytic T lymphocytes.
AB  - The human tyrosinase gene has been reported previously to code for two distinct
      antigens recognized on HLA-A2 melanoma cells by autologous cytolytic T
      lymphocytes (CTL). By stimulating lymphocytes of melanoma patient MZ2 with a
      subclone of the tumor cell line of this patient, we obtained a CTL clone that
      lysed this subclone but did not lyse other subclones of the same melanoma cell
      line. The sensitive melanoma subclone was found to express a much higher level of
      tyrosinase than the others, suggesting that the antigen recognized by the CTL
      might be encoded by tyrosinase. Transfection of a tyrosinase cDNA demonstrated
      that the CTL clone indeed recognized a tyrosinase product presented by HLA
      B*4403. The relevant antigenic peptide corresponds to residues 192-200 of the
      tyrosinase protein. Lymphoblastoid cells of the B*4402 subtype were not
      recognized by the CTL following incubation with the peptide. Nevertheless, by
      stimulating in vitro lymphocytes of a healthy HLA-B*4402 donor with autologous
      adherent cells pulsed with the same peptide, we obtained a CTL clone which
      recognized tumor cells expressing tyrosinase and HLA-B*4402. As HLA-B44 is
      expressed in 24% of Caucasians, the tyrosinase-B44 antigen may constitute a
      useful target for specific immunotherapy of melanoma.

PMID- 8566072
TI  - Activation via the antigen receptor is impaired in T cells, but not in B cells
      from patients with common variable immunodeficiency.
AB  - The patients included in this study belong to a subset of common variable
      immunodeficiency (CVID) patients whose peripheral blood T cells have a T cell
      receptor (TCR)-mediated activation defect leading to impaired expression of the
      interleukin (IL)-2 gene upon stimulation with recall antigens (tetanus toxoid,
      Escherichia coli) or superantigens (staphylococcal enterotoxins). In the present
      report we demonstrate that the patients' peripheral blood T cells failed to
      generate the second messenger inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)
      following stimulation with superantigen or mAb specific for the monomorphic
      region of the TCR beta-chain. Patients' T cell lines were also impaired in
      generating Ins(1,4,5)P3 when stimulated with tetanus toxoid-pulsed autologous
      monocytes. Addition of a second or third co-stimulatory signal provided by
      recombinant IL-2, CD28 or both had no effect on the Ins(1,4,5)P3 formation of the
      patients' antigen-driven T cell lines. The T cell activation defect, however, was
      not absolute, as Ins(1,4,5)P3 formation in the patients' T cells after
      phytohemagglutinin or aluminium fluoride stimulation was normal. The impairment
      in signal transduction via the T cell antigen receptor was limited to the
      patients' T cells, as no activation defect after ligation of surface
      immunoglobulin, the antigen receptor on B cells, could be detected.

PMID- 8566073
TI  - Self-renewal of B-1 lymphocytes is dependent on CD19.
AB  - The B-1 subset of B lymphocytes is maintained by self-renewal of mature cells,
      and this process may involve signaling through membrane immunoglobulin (mIg). We
      determined whether CD19, a membrane protein that co-stimulates B cells by mIg,
      has a role in this process. Pre-natal treatment of mice with 1D3, a rat anti
      mouse CD19 monoclonal antibody, down-regulated CD19 expression and reduced by
      sixfold the number of B-1a cells at birth; B-2 cells were relatively unaffected.
      Prolonged treatment of adult mice with 1D3 caused the loss of approximately 2%
      per day of peritoneal B-1a cells, without diminishing the recovery of splenic B-2
      cells. The loss of B-1a cells was associated with inhibition of their replication
      rather than with accelerated turnover. Therefore, CD19 is involved in the
      development and self-renewal of B-1a cells, perhaps through its ability to
      amplify signaling through mIgM.

PMID- 8566074
TI  - Characterization of the immunological memory state generated in mice susceptible
      to Leishmania major following exposure to low doses of L. major and resulting in
      resistance to a normally pathogenic challenge.
AB  - BALB/c mice are susceptible to a high-dose infection of the protozoan Leishmania
      major, which induces a parasite-specific antibody, Th2-like response, exclusive
      of a significant and protective cell-mediated Th1 component. We have shown, in
      contrast, that infection with a low number of parasites induces cell-mediated
      immunity exclusive of antibody production, and results in resistance to
      substantial subsequent high-dose infection. Low-dose exposure thus constitutes
      effective vaccination. In the present study, we analyze lymphokine production by
      parasite-specific T cells from those low-dose exposed, resistant mice and from
      normal, susceptible mice following high-dose infection. Two findings stand out.
      First, the parasite-specific T cells in mice rendered resistant appear not to be
      in an activated, effector state at the time of parasite challenge, as assessed by
      lack of lymphokine production on short-term stimulation with parasite antigens,
      but to be rather in a memory state. Second, the ratio of parasite antigen
      dependent production of interferon-gamma to that of interleukin-4 by spleen cells
      of low-dose exposed and normal mice upon high-dose challenge takes a dramatically
      different course. This ratio is similar in both groups of mice shortly after
      challenge, but increases dramatically in the resistant and declines dramatically
      in the control mice over a period of weeks, such that these ratios differ by
      about 60-fold 12 weeks after the high-dose challenge. In addition, we show that a
      similar state of resistance occurs following low-dose infection with a more
      virulent strain of L. major. In toto, our observations suggest that resistance
      may be generally achievable by low-dose exposure and may be associated with a
      memory state which, when activated by parasite challenge, results in the
      evolution of the response over weeks such that the protective, Th1 component
      becomes ever more dominant over the Th2 component.

PMID- 8566075
TI  - Non-tolerant B cells cause autoimmunity in anti-CD8 IgG2a-transgenic mice.
AB  - Using a pair of gamma 2a/chi immunoglobulin genes, transgenic mice were generated
      to study tolerance induction in B cells that express IgG2a autoantibodies. The
      transgenic IgG2a specifically binds CD8 alpha chains of the CD8.2 allotype
      expressed on the surface of CD8+ T cells, but not CD8 molecules expressed by the
      CD8.1 allele. Thus, IgG2a transgenic mice expressing the CD8.1 allele were used
      as controls to monitor B cell development and mice expressing CD8.2 were used to
      study B cell tolerance. Both types of mice showed transgenic gamma 2a expression
      on the surface of B cells. Expression of endogenous heavy chain alleles was
      strongly inhibited in immature B cell subsets, whereas mature B cells co
      expressed transgenic gamma 2a and endogenous IgM/D. The transgenic chi chain
      expression leads only to partial allelic exclusion of endogenous light chains. B
      cells that express high levels of transgenic CD8.2-specific IgG2a were identified
      using soluble CD8-Ig. In CD8.1+ and in CD8.2+ mice, we found no differences in
      expression and maturation of transgenic anti-CD8.2 IgG2a+ B cells. High levels of
      serum anti-CD8.2 IgG2a antibodies led to the elimination of CD8+ T cells, causing
      a severe defect in cytotoxic immune responses. These results show that tolerance
      induction is incomplete in the CD8.2+ mice, either because IgG2a+ B cells are
      resistant to censoring mechanisms or because the secreted CD8-specific IgG2a
      antibodies render the CD8 autoantigen inaccessible to the B cells. This contrasts
      strongly with the efficient induction of B cell tolerance in mice expressing anti
      CD8.2 IgM autoantibodies.

PMID- 8566076
TI  - Divergent evolution in the mechanisms controlling major histocompatibility
      complex class II gene transcription in mouse and human.
AB  - The expression of the major histocompatibility complex (MHC) class II gene family
      is developmentally regulated and, in general, in a coordinate manner. In this
      study, we show that the expression of the entire repertoire of human class II
      genes, otherwise transcriptionally silent in the bare lymphocyte syndrome-derived
      BLS1 cell line, can be rescued by somatic cell hybridization with normal mouse
      spleen cells. The analysis of the interspecies cell hybrids revealed a
      particularly important and unprecedented aspect. A return to the BLS1-like, human
      MHC class II-negative phenotype due to segregation of mouse chromosomes was
      accompanied in certain hybrids by loss of IE, but not IA cell surface antigen
      expression. At the molecular level, this was the result of lack of E alpha
      specific mRNA in the presence of E beta-, A alpha- and A beta-specific mRNA.
      Thus, the mouse trans-acting function operating across species barriers and able
      to complement the defect of human BLS1 cells diverged in mice to control Ea, but
      not Eb, Aa and Ab gene expression. These findings suggest that evolutionary
      pressure has maintained the expression of the MHC class II multigene family under
      the control of quite distinct species-specific transcriptional mechanisms.

PMID- 8566077
TI  - Specific expression of surface interferon-gamma on interferon-gamma producing T
      cells from mouse and man.
AB  - Interferon (IFN)-gamma is a potent immunoregulatory protein secreted by CD4+ and
      CD8+ T cells and by natural killer cells. Here, we show that IFN-gamma is
      specifically displayed at a low concentration on the cell surface of those
      activated T cells from mouse and man which express IFN-gamma. It is transiently
      expressed on the cell surface with kinetics similar to those of intracellular IFN
      gamma expression. Detectable surface IFN-gamma is not expressed by activated T
      helper (Th) cells producing other cytokines but which do not express IFN-gamma.
      Thus, surface IFN-gamma is the first available marker for live T lymphocytes
      expressing IFN-gamma, e.g. Th1 cells.

PMID- 8566078
TI  - Blimp-1 overcomes the block in IgM secretion in lipopolysaccharide/anti-mu
      F(ab')2-co-stimulated B lymphocytes.
AB  - A combination of signals transmitted through the antigen receptor, membrane-bound
      cell interaction molecules and cytokine receptors induces B cell proliferation
      and differentiation into immunoglobulin-secreting or memory cells. It has
      recently been suggested by Turner et al. (Cell 1994. 77: 297) that the complex
      changes in gene activities accompanying high levels of immunoglobulin secretion
      are under the common control of a master regulator, Blimp-1 (B lymphocyte-induced
      maturation protein). We show here that in naive mouse B cells stimulated with
      lipopolysaccharide (LPS) alone (which leads to high IgM production), Blimp-1 is
      highly expressed, while cells co-stimulated with LPS and anti-mu F(ab')2 show low
      levels of Blimp-1 mRNA and no longer secrete Ig. I gamma 1 sterile transcripts
      are, however, up-regulated after receptor co-ligation. Addition of interleukin
      (IL)-2 and IL-5 to LPS + anti-mu F(ab')2-treated primary B cells led to up
      regulation of Blimp-1 and IgM secretion. Transfection of a Blimp-1 expression
      vector also induced IgM secretion. The data indicate that Blimp-1 is an important
      regulator of immunoglobulin secretion by primary B cells, and suggest that its
      level of expression may determine the differentiation to Ig-secreting plasma
      cells or entrance and maintenance in the memory pool.

PMID- 8566079
TI  - Early development and progression of lymphocyte-stimulatory cross-reactive
      idiotypes expressed on antibodies to soluble egg antigens during Schistosoma
      mansoni infection of mice.
AB  - Idiotypes (Id) that stimulate immunoregulatory anti-Id T lymphocyte proliferation
      are expressed on murine and human antibodies (Ab) to soluble egg antigens (SEA)
      of Schistosoma mansoni. Kinetics of early expression of these stimulatory Id have
      now been studied using immunoaffinity-purified serum anti-SEA Ab from mice
      infected with S. mansoni for 6, 7, 8, 12, or 16 weeks. Rabbit anti-Id Ab specific
      for mouse anti-SEA Id expressed at 8 weeks post-infection (anti-8WkId)
      demonstrated the strongest interactions with Id present at 7 and 8 weeks post
      infection by competitive enzyme-linked immunosorbent assay. Anti-8WkId Ab reacted
      progressively less well with 12 WkId, 6WkId, and 16WkId. Splenocytes from mice
      infected for 8 weeks demonstrated the highest blast transformation responses in
      vitro to anti-SEA Id from mice infected for 6 weeks, while 7, 8, 12, and 16 weeks
      post-infection Id preparations stimulated progressively less proliferation. These
      data indicate that although eventual Id-associated immunoregulatory events
      contribute to chronicity in this disease, production of anti-SEA Ab that express
      stimulatory cross-reactive immunoregulatory Id comprises a substantial portion of
      the initial, acute anti-SEA response in mice infected with Schistosoma mansoni.
      Furthermore, either this particular Id-expressing response is not maintained, or
      its proportional presence is greatly diminished by the cumulative production of
      other multiple anti-SEA Ab during the establishment of chronicity, perhaps in
      response to its immunoregulatory influence very early in infection.

PMID- 8566080
TI  - Phenotypic and functional analysis of B lymphopoiesis in interleukin-7-transgenic
      mice: expansion of pro/pre-B cell number and persistence of B lymphocyte
      development in lymph nodes and spleen.
AB  - Transgenic mice in which mouse interleukin (IL)-7 cDNA is expressed under the
      control of the mouse major histocompatibility complex (MHC) class II (E alpha)
      promoter develop a lymphoproliferative disease characterized by the early
      polyclonal expansion of T cells followed in many cases by the development of
      lymphomas of immature B cells. Here, we have analyzed B cell development in these
      transgenic mice. Phenotypic analysis using monoclonal antibodies to B220, IgM,
      IgD, c-kit, IL-7 receptor, MHC class II, AA4.1, CD19, CD23, CD25, CD40 and CD43
      shows that B lymphopoiesis in the bone marrow is dramatically altered and the
      number of pro/pre-B and immature B cells is significantly increased.
      Interestingly, pro/pre-B and immature B cells persist in the spleens of adult
      transgenic mice and are also present in lymph nodes and blood. Cell cycle
      analysis of lymph node cells shows that subpopulations of developing B cells
      retain the cell cycle profiles of their bone marrow counterparts. Limiting
      dilution analysis shows that the number of clonable pre-B cells is significantly
      increased and that at limiting dilution, growth of transgenic pre-B cells is
      still dependent on exogenous IL-7. Using semiquantitative polymerase chain
      reaction (PCR) and in situ hybridization, the level of IL-7 transcripts in the
      spleen was found to decrease between 2 and 4 weeks in control mice with levels in
      transgenics mice being approximately 50 times greater. These transgenic mice
      represent an interesting model with which to study the effects of IL-7
      overexpression in the bone marrow and raise interesting questions regarding the
      regulation of B lymphopoiesis in normal mice.

PMID- 8566081
TI  - Comparison of CD28-B7.1 and B7.2 functional interaction in resting human T cells:
      phosphatidylinositol 3-kinase association to CD28 and cytokine production.
AB  - CD28 is a 44kDa homodimer present on T cells providing an important costimulatory
      signal for T cell proliferation, cytokine production and cytokine receptor
      expression. CD28 activation is mediated by interaction with its counter
      receptors, B7.1/CD80 and B7.2/B70/CD86. The biochemical basis of these co
      stimulatory signals are still poorly understood, particularly in resting T cells.
      However, various biochemical pathways such as tyrosine phosphorylation,
      phospholipase C, sphingomyelinase and phosphatidylinositol 3-kinase (PI3-K)
      activation have been reported to play a role in CD28 signaling in tumor T cell
      lines and CD28-transfected cells or pre-activated T cells. In addition, recent
      reports propose that CD28-B7.1 and B7.2 interaction could be involved in the
      production of Th1 and Th2 cytokines, respectively, but the putative biochemical
      basis for these different functions is still unknown. We have analyzed the
      functional and molecular consequences of CD28 activation by B7.1 and B7.2 in
      human resting T cells. We demonstrate in this report that both CD28-B7.1 and CD28
      B7.2 interactions induce the association of PI3-K to CD28 in the CD4
      subpopulation, whereas it was barely detectable in CD8 cells. This association
      involves the binding of the src homology domain 2 (SH2) of p85 to tyrosine
      phosphorylated CD28 and does not require pre-activation by CD3-T cell receptor.
      Worthmannin, a specific inhibitor of PI3-K enzymatic activity within the
      nanomolar range also inhibits the interleukin-2 production induced by
      costimulation mediated by either the B7.1- and B7.2-transfected cells or CD28
      monoclonal antibodies. The only slight difference between B7.1 and B7.2
      costimulation is the IC50 of worthmannin being 25 and 110 nM, respectively, which
      could suggest differences in their activation of the T cell PI3-K.

PMID- 8566082
TI  - T cell recognition of penicillin G: structural features determining antigenic
      specificity.
AB  - Penicillin G (Pen G) and other beta-lactam antibiotics frequently induce allergic
      reactions constituting typical examples of human immune responses to haptens. In
      fact, penicillins represent a unique set of haptens with outstanding structural
      variability on the basis of an identical protein-reactive beta-lactam containing
      backbone. Although both cellular and humoral responses are involved in drug
      induced allergies, little is known about the T cell reactivity to penicillins. To
      understand which structural features determine antigenic specificity, we isolated
      a panel of MHC-restricted, Pen G-reactive T cell clones from different penicillin
      allergic patients and tested them for their capacity to proliferate in the
      presence of other penicillin derivatives. We found that the antigenic epitope
      consists of both the amide-linked side chain, which is different in every member
      of the penicillin family, as well as the thiazolidine ring common to all
      penicillin derivatives. We also demonstrated the presence of two different types
      of penicillin-specific T cells, one dependent, and the other independent of
      antigen processing by autologous antigen-presenting cells. Our data strongly
      suggest that penicillins form part of the epitopes contacting the antigen
      receptors of T cells.

PMID- 8566083
TI  - Modulation of expression of the anti-inflammatory cytokines interleukin-13 and
      interleukin-10 by interleukin-3.
AB  - Interleukin (IL)-4, IL-10 and IL-13 are cytokines with potent anti-inflammatory
      activities. Prevention of pathological inflammation at mucosal surfaces appears
      to be due, in part, to the presence of these cytokines. One potential source for
      these cytokines is the mast cell which resides at mucosal surfaces. Demonstrated
      in this report are the findings that bone marrow-derived mucosal-like mast cells
      constitutively expressed IL-13 whereas bone marrow-derived connective tissue-like
      mast cells demonstrated IL-13 transcription only after Fc epsilon RI-mediated
      activation or the addition of exogenous IL-3. A similar pattern of expression of
      IL-10 by these mast cell types was also evident and matches that of IL-4
      previously reported. Intracellular cytokine staining indicated that IL-10 protein
      is constitutively expressed by the bone marrow-derived mucosal-like mast cells
      but is only evident in the bone marrow-derived connective tissue-like mast cells
      after induction with IL-3. The increase of IL-13 and IL-10 transcripts in the
      connective tissue-like mast cells following IL-3 treatment is not mast cell
      specific, in that splenic and bone marrow cells also demonstrated the same
      phenomenon. These data suggest that mucosal mast cells may have a constitutive
      repertoire of Th2 cytokines with potential anti-inflammatory activity, while
      connective tissue mast cells may not. However, production of such cytokines can
      be induced in the connective tissue mast cell and other cell types of the immune
      response by the addition of IL-3.

PMID- 8566084
TI  - Anti-CD5 extends the proliferative response of human CD5+ B cells activated with
      anti-IgM and interleukin-2.
AB  - The CD5 T cell glycoprotein which is expressed by a subset of B cells has been
      shown to be involved in T cell activation and proliferation. No similar studies,
      to date, have addressed the role of CD5 on the B cell subset. CD5+ and CD5- B
      cells were sorted and stimulated with anti-CD5 monoclonal antibody (mAb) in
      vitro. The activation and proliferative responses of these two populations, as
      measured by analysis of proliferation marker, did not differ following anti-mu
      and interleukin (IL)-2 stimulation. The addition of anti-CD5 did not change the
      responsiveness of such activated CD5+ B cells but resulted in a decrease in CD25
      expression. Pre-activation of B cells with phorbol 12-myristate 13-acetate, which
      increased CD5 expression, failed to alter the proliferative response of CD5+ B
      cells to anti-mu and IL-2 with or without addition of anti-CD5 mAb. Anti-mu and
      IL-2 treatment of CD5+ cells resulted in optimal proliferation measured at day 3
      which decreased by day 6. However, addition of anti-CD5 mAb at day 3 prevented
      this decline in proliferative response. This dose-dependent effect was observed
      only when the anti-CD5 mAb was presented to the B cells in cross-linked form. Co
      stimulation of CD5 did not lower the threshold of antigen to which the B cells
      responded. Taken together, these data support a functional role for CD5 on B
      cells acting as an accessory signal, following their primary activation through
      the B cell receptor complex and highlight differences in the role of CD5
      associated with the T cell receptor complex.

PMID- 8566085
TI  - The VDJ repertoire expressed in human preB cells reflects the selection of bona
      fide heavy chains.
AB  - In early steps of B cell differentiation, mu chains are transiently expressed in
      association with a surrogate light chain (psi L) composed of the lambda-like and
      VpreB monomorphic polypeptides, thus forming a putative preB receptor. Using a
      monoclonal anti-VpreB antibody, preB cells were isolated from two adult human
      bone marrow samples and their VDJ repertoire analyzed at the transcription level.
      All VH families were identified and further analysis focused on VH3 sequence
      analysis of 37 distinct VDJ cDNA clones. The VH3 genes expressed in the two bone
      marrow samples were also encountered in fetal liver and adult peripheral blood
      lymphocytes with a roughly similar contribution of 3.30, 3.23, 3.9 and 3.53. The
      characteristic features of the preB repertoire as compared to the activation B
      repertoire include the quasi absence of somatic mutations, limited N diversity
      and a shorter third complementarity-determining region (CDR3). It also
      significantly differs from the fetal repertoire, which makes higher usage of DQ52
      and has CDR3 of even shorter lengths. The almost constant presence of glycine
      residues in the CDR3 and predominance of JH4 with a low level of DQ52 DH usage,
      suggest that preB cell clones are submitted to an initial selective pressure
      which should be antigen independent. The bona fide heavy chains would be merely
      selected for their ability to interact with the surrogate light chains, thus
      shaping the repertoire that will be co-expressed with immunoglobulin light chains
      in IgM molecules.

PMID- 8566086
TI  - Human eosinophils express messenger RNA encoding RANTES and store and release
      biologically active RANTES protein.
AB  - Eosinophils synthesize and store various cytokines with potential autocrine
      activity. We hypothesized that eosinophils synthesize and store RANTES, a CC
      chemokine with potent eosinophil chemotactic activity. Expression of RANTES mRNA
      in highly purified eosinophil populations was detected by reverse transcription
      followed by polymerase chain reaction analysis. In situ hybridization (ISH) with
      35S-labeled RANTES-specific riboprobes showed that 6.8-10% of peripheral blood
      eosinophils obtained from atopic subjects expressed RANTES mRNA, increasing to
      25% after incubation (16 h) with interferon (IFN)-gamma, but not ionomycin in
      vitro. Peripheral blood eosinophils also showed specific immunoreactivity with an
      anti-RANTES monoclonal antibody, consistent with translation of the mRNA. By
      enzyme-linked immunosorbent assay, blood eosinophils were shown to contain a
      median of 7300 pg (range 5200-8800) RANTES per 10(6) cells, of which a mean of
      24% was released into culture supernatants after stimulation of the cells with
      serum-coated particles in vitro. These culture supernatants exhibited eosinophil
      chemotactic activity which was inhibited (mean 68%) by a specific anti-RANTES
      antibody. Sequential immunocytochemistry and ISH on biopsies obtained from
      allergen-induced late-phase cutaneous reactions showed that 55-75% of the
      infiltrating RANTES mRNA+ cells were EG2+ eosinophils. Allergen, but not diluent
      challenge, was also associated with a time-dependent increase in the number of
      cells showing RANTES immunoreactivity. Of these cells, 55% were identified as
      eosinophils by morphological criteria. Thus, human eosinophils have the capacity
      to synthesize, store and secrete physiologically relevant quantities of RANTES,
      and may therefore be an important source of this chemokine in allergic
      inflammation.

PMID- 8566087
TI  - Calcium-dependent lectin activity with novel distribution on thymocyte subsets.
AB  - In this study we use carbohydrate probes to search for novel cell surface lectins
      in the immune system. Many carbohydrate binding proteins are members of the C
      type lectin superfamily, whose ligand binding is dependent on calcium. To
      identify potential new members of this superfamily, fluorescein-conjugated
      carbohydrate polymers were used to probe for calcium-dependent cell surface
      binding. This approach offers advantages over the use of monoclonal antibody
      probes since only carbohydrate binding proteins would be identified. We have
      identified a cell surface lectin, referred to as thy-lec, detected by the probe
      fucoidan-fuorescein isothiocyanate. This calcium-dependent lectin has a novel
      distribution on thymocyte subsets. It is present on the surface of immature
      CD4+8+ and on large, cycling CD4-8- cells and CD8+4- cells, but not on small,
      mature phenotype CD8+4- or CD4+8- thymocytes. This lectin is not found on mature
      T cells or other leukocytes in lymph nodes, spleen or bone marrow. It is proposed
      that this novel cell surface has a function in the maturation of T cells in the
      thymus.

PMID- 8566088
TI  - Proximity relationships between the type I receptor for Fc epsilon (Fc epsilon
      RI) and the mast cell function-associated antigen (MAFA) studied by donor
      photobleaching fluorescence resonance energy transfer microscopy.
AB  - Clustering of the mast cell function-associated antigen (MAFA) on the surface of
      rat mucosal type mast cells line 2H3 (RBL-2H3) leads to suppression of the
      secretory response induced by the type I Fc epsilon receptor (Fc epsilon RI). In
      order to establish a possible association between MAFA and Fc epsilon RI we
      measured fluorescence resonance energy transfer (FRET) between the MAFA-specific
      monoclonal antibody (mAb) G63 and Fc epsilon RI-bound ligands as well as between
      Fc epsilon RI-bound ligands themselves using the donor photobleaching FRET
      (pbFRET) technique. Average FRET efficiencies between 6 and 9% were determined
      after low-temperature incubation with fluorescent dye conjugated mAb G63 bound to
      MAFA (donor) and IgE bound to Fc epsilon RI (acceptor) on RBL-2H3 cells.
      Subsequent cross-linking of IgE by a polyvalent antigen caused no change in FRET
      efficiencies. These results suggest that the MAFA is located in the vicinity of
      the Fc epsilon RI on resting cells, and that clustering of the Fc epsilon RI
      leads to no significant change in the proximity of the two molecular species. In
      view of the sequence motif identified in the cytosolic tail of the MAFA and the
      observed changes in its phosphorylation upon antigen stimulation (Guthmann et
      al., Proc. Natl. Acad. Sci. USA 1995, 92: 9397-9401), the present study suggests
      that the secretory response inhibition by MAFA interferes with the signal
      transduction cascade initiated via the Fc epsilon RI. An additional finding was
      that clustering of the Fc epsilon RI by antigen showed a clear increase in the
      efficiency of FRET between Fc epsilon RI-bound IgE molecules conjugated with
      fluorescent donor and acceptor.

PMID- 8566089
TI  - Expression and function of Fas antigen on activated murine B cells.
AB  - We have studied the expression and function of Fas antigen on murine B
      lymphocytes. While Fas was present on only a few B cells in the bone marrow,
      spleen, lymph node or peripheral blood, its expression could be strongly up
      regulated by stimulation with soluble CD40 ligand (CD40L). Treatment with anti
      IgM and interleukin-4 (IL-4) alone did not induce significant Fas expression but
      enhanced CD40L-mediated up-regulation of Fas expression. The T cell-derived
      signal via CD40 is therefore a potent inducer of Fas expression by B lymphocytes.
      The sensitivity to Fas-mediated apoptosis was found to depend on the duration of
      B cell activation. B cells activated for 1 day were resistant to Fas-mediated
      cell death, whereas B cells activated for 3 days were relatively sensitive.
      Interestingly, different sensitivity to Fas-mediated death signal was observed in
      2-day activated B cells. It was found that B cells stimulated with CD40 L alone
      were more sensitive to Fas-mediated apoptosis than were cells stimulated with
      CD40L plus anti-IgM or IL-4, and in particular, the combination of the two. The
      greater sensitivity exhibited by B cells stimulated with CD40L alone seems to be
      related to limited activation of these cells in the absence of additional
      stimulation. Co-stimulation of B cells in the presence of CD40L and anti-Fas
      antibody resulted initially in activation of B lymphocytes, as reflected by the
      expression of activation markers and cell growth, but this was followed by growth
      inhibition and cell death. The data demonstrate that the B cell response can be
      regulated positively and negatively by signaling through CD40 and Fas antigens,
      respectively.

PMID- 8566090
TI  - Differences and similarities in the A2.1-restricted cytotoxic T cell repertoire
      in humans and human leukocyte antigen-transgenic mice.
AB  - HLA-A2.1-binding peptides (n = 38) were screened for immunogenicity with human
      peripheral blood mononuclear cells in cytotoxic T lymphocyte (CTL) induction
      experiments in vitro and with splenocytes from HLA-A2.1/Kb transgenic mice
      following immunization in vivo. These data were compiled and analyzed to
      determine the level of overlap between the A2.1-restricted CTL repertoire of
      A2.1/Kb-transgenic mice and A2.1+ humans. In both humans and mice, a major
      histocompatibility complex affinity threshold of approximately 500 nM appears to
      determine the capacity of a peptide to elicit a CTL response. Good concordance
      between the human data in vitro and mouse data in vivo was observed with 85% of
      the high-binding peptides, 58% of the intermediate binders, and 83% of the
      low/negative binders. Although some peptides immunogenic for mouse CTL but not
      for humans (and vice versa) could be identified, the data as a whole suggest an
      extensive overlap between T cell receptor repertoires of mouse and human CTL and
      support the use of HLA-transgenic mice for the identification of potential human
      CTL epitopes.

PMID- 8566091
TI  - Physical withdrawal in rats tolerant to delta 9-tetrahydrocannabinol precipitated
      by a cannabinoid receptor antagonist.
AB  - Tolerance to delta 9-tetrahydrocannabinol (delta 9-THC) was produced in rats by
      twice daily injections (15 mg/kg i.p.) for 6.5 days. Administration of the
      cannabinoid antagonist SR141716A (i.p. or i.c.v.) induced a profound precipitated
      withdrawal syndrome in delta 9-THC-tolerant animals. The syndrome was
      characterized by a disorganized pattern of constantly changing brief sequences of
      motor behavior. Autonomic signs were not evident. THC-tolerant animals that were
      treated with vehicle remained quiet throughout the observation period.

PMID- 8566092
TI  - Characterization of a postjunctional 5-HT receptor mediating relaxation of guinea
      pig isolated ileum.
AB  - The 5-HT receptor mediating postjunctional relaxation of precontracted guinea-pig
      ileum has been characterized using several agonists and antagonists. Substance P
      precontracted tissues were potently relaxed by 5-HT (5-hydroxytryptamine,
      serotonin), 5-CT (5-carboxamidotryptamine) and several other indoles. The rank
      order of potency, with pEC50 values in parentheses, was 5-CT (7.6) > 5
      methoxytryptamine (5.7) > 5-HT (5.5) > alpha-methyl-5-HT (4.7) > 2-methyl-5-HT (<
      4.0) = tryptamine (< 4.0) = N,N-dimethyl-tryptamine (< 4.0) = N,N-dimethyl-5-HT
      (< 4.0) = dipropyl-5-CT (< 4.0) = sumatriptan (< 4.0). 8-OH-DPAT (8-hydroxy-2-(di
      n-propylamino)-tetralin) acted as a potent (6.3), but partial, agonist with
      respect to 5-HT. The responses to 5-CT were antagonized by several compounds with
      the following rank order of affinity, with pKB values in parentheses: LSD
      (lysergic acid diethylamide; 8.1) = mesulergine (7.8) > methysergide (7.6) =
      spiperone (7.6) > clozapine (7.3) >> (-)-pindolol (< 6.0) > ketanserin (< 6.0) =
      ondansetron (< 6.0) = GR 113808 ([1-(2-methane-sulphonamido-ethyl)-piperidin-4
      yl]-methyl-in dole-3- carboxylate maleate; < 6.0). The relaxant responses to 5-HT
      were also resistant to tetrodotoxin. These data are consistent with a functional
      5-HT receptor, mediating relaxation of guinea-pig ileum, which exhibits an
      operational profile similar to that of the cloned guinea-pig 5-ht7 receptor. This
      study, therefore, provides evidence for a functional correlate of the 5-ht7 gene
      product.

PMID- 8566093
TI  - Complex I inhibitor effect on the nigral and striatal release of dopamine in the
      presence and absence of nomifensine.
AB  - The effect of inhibitors of complex I respiratory chain--1-methyl-4
      phenylpyridinium ion (MPP+, 10 microM) and rotenone (100 microM)--on the release
      and metabolism of dopamine was studied by in vivo microdialysis in the striatum
      and substantia nigra. Both compounds produced a marked increase in the release of
      dopamine in the striatum and substantia nigra, which was diminished when
      nomifensine (20 microM) was included in the perfusion fluid. The 3,4
      dihydroxyphenylacetic acid (DOPAC) extracellular output was decreased under MPP+
      (10 microM) perfusion in the striatum and substantia nigra, in the presence and
      in the absence of nomifensine (20 microM). However, perfusion of rotenone (100
      microM) increased or had no effect on DOPAC outflow. Homovanillic acid levels
      were affected in the same way as DOPAC levels, but the changes were always much
      less pronounced. These results suggest that the neurotoxic action of MPP+ or
      rotenone is similar in the striatum and substantia nigra, indicating the
      importance of the dopamine uptake system in this neurotoxic action of MPP+ or
      rotenone, also suggesting that the dopamine uptake system could have low
      selectivity and also transports other substances such as rotenone.

PMID- 8566094
TI  - Respiratory effects produced by microinjection of L-glutamate and an uptake
      inhibitor of L-glutamate into the caudal subretrofacial area of the medulla.
AB  - The purposes of our study were to determine the type of respiratory changes that
      would occur when either an excitatory amino acid receptor agonist or an uptake
      inhibitor was administered into the caudal subretrofacial area. This was done by
      microinjecting either L-glutamate or L-pyrrolidine-2,4-dicarboxylate (L-trans-2,4
      PDC) into the caudal subretrofacial area while monitoring tidal volume,
      respiratory rate, mean arterial blood pressure and heart rate. Bilateral
      microinjection of 2.5 nmol of L-glutamate into the caudal subretrofacial area
      produced apnea in eight of eight animals tested, and the duration of apnea was 27
      +/- 2 s. To determine the type of L-glutamate receptor responsible for mediating
      the apneic response, antagonists of the N-methyl-D-aspartate (NMDA) and non-NMDA
      receptor, namely, 3-[(RS)-carboxypiperazin-4-yl]-propyl-phosphonic acid (CPP),
      and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively, were tested.
      Neither antagonist in doses that blocked NMDA (in the case of CPP) and amino-3
      hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) (in the case of CNQX) blocked
      apnea elicited by L-glutamate. In addition, kynurenic acid, an antagonist of NMDA
      and non-NMDA ionotropic receptors, failed to block the effect of L-glutamate.
      Microinjection of the metabotropic receptor agonist drug, trans-L-1-amino-1,3
      cyclopentone-dicarboxylic acid (L-trans-ACPD), into the caudal subretrofacial
      area failed to have any effect on respiratory activity. Because of the inability
      to block the effect of L-glutamate in the caudal subretrofacial area, and the
      lack of effect of L-trans-ACPD, the data suggest that the apneic response
      produced by L-glutamate is mediated by an as yet undefined receptor.
      Microinjection of the L-glutamate uptake inhibitor, L-trans-2,4-PDC, was found to
      produce apnea. Using the dose of 0.5 nmol of L-trans-2,4-PDC, we examined the
      type of excitatory amino acid receptor that mediated the response. Neither
      pretreatment with the NMDA receptor antagonist, CPP, nor the non-NMDA receptor
      antagonist, CNQX, affected L-trans-2,4-PDC-induced apnea. However, combined use
      of these two antagonists prevented L-trans-2,4-PDC-induced apnea. These data
      suggest that the effect of synaptically released exitatory amino acid at the
      caudal subretrofacial area on breathing is apnea, and that this effect is
      mediated by simultaneous activation of both NMDA and non-NMDA ionotropic
      receptors.

PMID- 8566095
TI  - Differential effect of buspirone and diazepam on negative contrast in one-way
      avoidance learning.
AB  - The main aim of the present work was to investigate the effect of buspirone, a 5
      HT1A receptor agonist, on successive negative contrast in one-way avoidance
      learning. Successive negative contrast was induced by shifting rats from a large
      reward (30 s spent in the safe compartment) to a small reward (1 s). Acute
      administration of buspirone (0.25, 0.5, 0.75 and 1.0 mg/kg i.p.) did not
      attenuate the contrast effect, as opposed to that observed for diazepam (1 mg/kg
      i.p.). The highest dose of buspirone used, however, did interfere with the
      learning of the avoidance response itself. Chronic buspirone (20 days, 0.5 and
      0.75 mg/kg i.p.) did not have any effect on successive negative contrast either.
      Overall, these results could suggest that the 5-HT1A receptor is not involved in
      the negative contrast effect studied, quite different to that observed for the
      gamma-aminobutyric acid (GABA) system. The findings are compared to results
      obtained with animal models selectively sensitive to some anxiolytic drugs, as
      are the so-called 'conflict models'.

PMID- 8566096
TI  - Angiotensin II-induced responses in vascular smooth muscle cells: inhibition by
      non-peptide receptor antagonists.
AB  - The present study investigates the effect of angiotensin II and LR-B/081 (-methyl
      2-[[4-butyl-2-methyl-6-oxo-5-[[2'-(1H-tetra-zol-5-yl) [1,1'-biphenyl]-4-yl]
      methyl]-1(6H)-pyrimidinyl] methyl]-3-thiophenecarboxylate), a novel non-peptide
      angiotensin II receptor antagonist, on both early and late responses in rat
      vascular smooth muscle cells. Angiotensin II induced a rapid and transient
      elevation of inositol trisphosphate intracellular levels, triggered the release
      of both prostaglandin E2 and prostaglandin I2 (EC50 = 21 +/- 3 and 16 +/- 2 nM,
      respectively), and, in long-term studies, increased leucine and thymidine
      incorporation. All angiotensin II effects were antagonized by LR-B/081 and
      losartan, the reference non-peptide angiotensin AT1-selective receptor
      antagonist, whereas they were unaffected by PD123177 (1-(4-amino-3
      methylphenyl)methyl-5-diphenylacetyl-4,5,6,7-tetr ahy dro-1H- imidazo[4,5
      c]pyridine carboxylic acid), a non-peptide angiotensin AT2-selective receptor
      antagonist. LR-B/081 displayed a much higher potency than losartan in inhibiting
      angiotensin II-induced prostaglandin E2 (IC50 = 0.15 +/- 0.02 and 39 +/- 9 nM,
      respectively) and prostaglandin I2 release (IC50 = 0.18 +/- 0.04 and 134 +/- 40
      nM, respectively) and was also more potent in blocking the increase in protein
      synthesis (IC50 = 242 +/- 119 nM and 1221 +/- 687 nM, respectively). Moreover, LR
      B/081 and losartan blocked the response to angiotensin III but failed to inhibit
      the prostaglandin release stimulated by vasopressin or the mitogenic effect of
      serum. LR-B/081 and losartan were devoid of intrinsic properties in the
      experimental conditions employed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8566097
TI  - Bradykinin-induced release of thromboxane B2 into bronchoalveolar lavage fluid of
      guinea pigs: relationship to airflow obstruction.
AB  - The aim of this study was to evaluate the role of thromboxane A2 in bradykinin
      induced airflow obstruction in guinea pig in vivo. Airway insufflation pressure
      (Pi) was measured to assess airflow obstruction and the thromboxane B2 (a stable
      metabolite of thromboxane A2) concentration in bronchoalveolar lavage fluid was
      determined by radioimmunoassay. The animals were pretreated with propranolol (1
      mg/kg i.v.) and suxamethonium (5 mg i.v.) prior to bradykinin administration.
      Bradykinin instillation into the trachea (300 nmol) induced a Pi increase (47.5
      +/- 8.3 cm H2O versus 23.8 +/- 1.5 in sham) and significant thromboxane B2
      release into bronchoalveolar lavage fluid (79 +/- 19 pg/ml versus 19 +/- 6 in
      sham). A thromboxane synthase inhibitor (OKY-046, 30 mg/kg i.v.; ((E-E)-3-[p(1H
      imidazole-1-yl-methyl) phenyl]-2-propenoic acid hydrochloride mono-hydrate)) or a
      thromboxane A2 receptor antagonist (ICI192,605, 0.5 mg/kg i.v.; (4-(Z)-6-(2-o
      chloro-phenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid)) reduced the
      Pi increase evoked by bradykinin (38.7 +/- 3.8 and 40.6 +/- 3.8 cm H2O,
      respectively). OKY-046 abolished the thromboxane B2 release. A platelet
      activating factor receptor antagonist, WEB2086 (1 mg/kg i.v.; (3-[4
      (chlorophenyl)-9-methyl-6H-thienol [3,2-f][1,2,4]trizolo-[4,3-a][1,4] diazepin-2
      yl]1-4-(4-morpholinyl)-1-propanon) did not significantly affect any measured
      parameter. We conclude that, in guinea pigs, bradykinin-induced airway effects
      are associated with a local thromboxane A2 release.

PMID- 8566098
TI  - Characterization of two novel sigma receptor ligands: antidystonic effects in
      rats suggest sigma receptor antagonism.
AB  - The novel sigma receptor ligands, N(-)[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2
      (dimethylamino)ethylamine (BD1047) and 1(-)[2-(3,4-dichlorophenyl)ethyl]-4
      methylpiperazine (BD1063), were characterized in rats using binding assays and
      behavioral studies. In radioligand binding studies, the novel ligands showed
      marked selectivity for sigma binding sites, generally having a 100-fold or better
      affinity for sigma sites compared to nine other tested receptors (opiate,
      phencyclidine, muscarinic, dopamine, alpha 1-, alpha 2-, beta-adrenoceptor, 5
      HT1, 5-HT2); the only exception was the affinity of BD1047 for beta
      adrenoceptors. Competition assays further revealed that the drugs interacted with
      both sigma 1 and sigma 2 binding sites. Although both drugs had preferential
      affinities for sigma 1 sites, BD1047 exhibited a higher affinity for sigma 2
      sites than BD1063. In behavioral studies, BD1047 and BD1063 had no effects on
      their own when unilaterally microinjected into the red nucleus of rats, but both
      compounds attenuated the dystonia produced by the high affinity sigma ligands, di
      o-tolylguanidine (DTG) and haloperidol. BD1047 and BD1063 dose-dependently
      attenuated the dystonia produced by DTG, suggesting a receptor-mediated
      mechanism, and the dose curve for DTG was shifted to the right in the presence of
      the novel ligands. BD1047 and BD1063 appear to act as antagonists at sigma sites
      and may represent promising new tools for probing other functional effects
      associated with sigma binding sites.

PMID- 8566099
TI  - Role of endothelin-1 in hypertension induced by long-term inhibition of nitric
      oxide synthase.
AB  - We examined the effect of long-term nitric oxide (NO) synthase inhibition on
      vascular and renal endothelin-1 levels and evaluated the antihypertensive effect
      of endothelin ETA receptor antagonist FR139317 ((R)2(-)[(R)-2(-)[(S)-2(-)[[1
      (hexahydro-1H-azepinyl)]- carbonyl]amino-4-methyl-pentanoyl]amino-3(-)[3-(1
      methyl-1H- indolyl)]propionyl]amino-3-(2-pyridyl) proprionic acid] on rats in
      which NO synthase was blocked. Chronic NO blockade was produced by oral
      administration of the NO synthase inhibitor NG-nitro-L-arginine for 4 weeks,
      which produced sustained hypertension. At the end of this time, there were no
      significant changes in aortic and renal immunoreactive-endothelin levels between
      NG-nitro-L-arginine-treated hypertensive rats and normotensive control rats.
      Intravenous injection of FR139317 (10 mg/kg), which had a sufficient hypotensive
      effect on deoxycorticosterone acetate-salt hypertensive rats, to NG-nitro-L
      arginine-treated hypertensive rats produced only a moderate hypotensive effect,
      to the same degree as seen in normotensive rats. The results indicate that long
      term NO synthase inhibition did not affect vascular and renal endothelin-1 levels
      in these rats. It seems likely that endothelin-1 and ETA receptors do not
      contribute to the sustained hypertension induced by NO synthesis blockade.

PMID- 8566100
TI  - The effect of K+ channel openers on submucosal gland function and epithelial
      transport of the ferret trachea, in vitro.
AB  - The effects of three K+ channel openers on lysozyme output from submucosal gland
      serous cells and epithelial albumin transport following maintained submaximal
      stimulation by the secretagogues methacholine and phenylephrine were examined in
      the ferret trachea in vitro preparation. The K+ channel openers Ro 31-6930, 2-(6
      cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-pyridine 1-oxide (10 nM-10 microM),
      levcromakalim, BRL38227 (10 nM-10 microM) and pinacidil (100 nM-10 microM)
      produced a concentration dependent inhibition of (20 microM) methacholine-induced
      lysozyme output, with pD2 values of 7.64, 7.72 and 7.28 respectively. Ro 31-6930
      (10 nM-10 microM), levcromakalim (10 nM-10 microM) and pinacidil (1 nM-10 microM)
      also produced a concentration dependent inhibition of (100 microM) phenylephrine
      induced lysozyme output, with pD2 values of 7.64, 6.55 and 9.16 respectively.
      Furthermore, glibenclamide (1 microM) produced a modest attenuation of the K+
      channel opener effects on secretagogue-induced lysozyme output. All three K+
      channel openers failed to produce any significant change in either methacholine
      or phenylephrine-induced albumin outputs. The K+ channel openers exerted marked
      effects on airway secretion processes, suggesting that these compounds may have
      an antisecretory effect. The relevance of the use of the K+ channel openers in
      airway disease remains to be determined.

PMID- 8566101
TI  - Blockade of morphine-induced place preference by diazepam in mice.
AB  - The effects of diazepam on morphine-induced place preference were examined in
      mice. Pretreatment with diazepam (2 mg/kg i.p.) 30 min prior to morphine
      injection significantly abolished the morphine (5 mg/kg s.c.)-induced place
      preference, and this effect of diazepam was antagonized by pretreatment with
      flumazenil. In addition, pretreatment with diazepam prevented the morphine (5
      mg/kg s.c.)-induced increase in dopamine turnover in the limbic forebrain. These
      results suggest that pretreatment with diazepam may suppress the rewarding
      effects of morphine.

PMID- 8566102
TI  - Induction of mating behavior by apomorphine in sexually sated rats.
AB  - We have tested the hypothesis, suggested by our previous neurochemical studies,
      that the inhibition of sexual behavior that follows unrestricted mating could be
      caused by a blockade of dopaminergic transmission. Male rats were allowed to
      copulate until they reached a satiety criterion. The following day, after
      verification that they were sexually inactive, the animals were injected with the
      dopamine agonist, apomorphine, at doses of 80, 200, and 500 micrograms/kg body
      weight and their behavior with receptive females was recorded. A bell-shaped dose
      response curve was found, with the 200 micrograms/kg dose having the maximal
      stimulatory effects on mating. Whereas these findings seem to support the above
      hypothesis, it should be noted that apomorphine treatments were unable to restore
      fully the copulatory pattern shown by sexually rested animals. This could be due
      to several factors including the interference of apomorphine-induced
      stereotypies, and/or the involvement of additional transmitter systems in the
      mechanisms of sexual satiety.

PMID- 8566103
TI  - 5-Hydroxytryptamine induces endothelium-independent relaxations of sheep
      pulmonary vein: role of cyclic nucleotide.
AB  - 5-Hydroxytryptamine produced concentration-dependent relaxations in isolated
      sheep pulmonary vein, which were insensitive to removal of the endothelium. 5
      Hydroxytryptamine stimulated concentration-dependent increases of cyclic AMP
      levels in the pulmonary vein, and there was a significant linear correlation
      between relaxations elicited by 5-hydroxytryptamine and tissue cyclic AMP
      formations. The soluble guanylate cyclase inhibitor methylene blue (10 microM)
      failed to block 5-hydroxytryptamine-induced relaxations. The results suggest that
      5-hydroxytryptamine-induced relaxations of sheep pulmonary vein are mediated, at
      least in part, by increases of tissue cyclic AMP levels.

PMID- 8566104
TI  - Nitric oxide and sensory afferent neurones modulate the protective effects of low
      dose endotoxin on rat gastric mucosal damage.
AB  - Pretreatment (1 h) with low doses (5-40 micrograms/kg i.p.) of Escherichia coli
      endotoxin dose dependently reduced the gastric mucosal damage induced by a 10 min
      challenge with 1 ml ethanol (50% and 100%) in conscious rats. Treatment with the
      nitric oxide synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 5 and
      10 mg/kg i.p.), significantly inhibited the protective effects of endotoxin (40
      micrograms/kg i.p.). The actions of L-NAME were reversed by the prior
      administration of L-arginine (100 mg/kg i.p.). The protective effects of
      endotoxin were not influenced by pretreatment with dexamethasone (5 mg/kg s.c.
      twice) or indomethacin (5 mg/kg s.c.). However, ablation of sensory afferent
      neurons by capsaicin pretreatment (20, 30 and 50 mg/kg s.c.) abolished the mucosa
      protective effects of endotoxin (40 micrograms/kg). These findings suggest that
      the protection elicited by low doses of endotoxin against ethanol-induced mucosal
      damage involves synthesis of nitric oxide and activation of sensory neurones.

PMID- 8566105
TI  - The spin trap reagent alpha-phenyl-N-tert-butyl nitrone prevents 'ecstasy'
      induced neurodegeneration of 5-hydroxytryptamine neurones.
AB  - Administration of a single dose (10 mg/kg i.p.) of 3,4-methylenedioxy
      methamphetamine (MDMA or 'ecstasy') produced a 40% loss of 5-hydroxytryptamine (5
      HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cortex and
      hippocampus of Dark Agouti rats 7 days later. Binding of [3H]paroxetine to the
      presynaptic 5-HT nerve terminals in cortex was decreased by approximately 30%.
      Injection of the spin trap reagent alpha-phenyl-N-tert-butyl nitrone (PBN; 150
      mg/kg i.p.) 10 min prior and 120 min post MDMA administration totally prevented
      the loss in [3H]paroxetine binding in the cortex and attenuated the loss of 5-HT
      and 5-HIAA in both brain regions. PBN alone had no effect on [3H]paroxetine
      binding or brain 5-HT content. These data suggest that MDMA produces
      neurodegeneration of 5-HT neurones because of reactive free radical formation.

PMID- 8566106
TI  - Modulation of glutamate release by a kappa-opioid receptor agonist in rodent and
      primate striatum.
AB  - The influence of the kappa-opioid receptor agonist, enadoline, on endogenous
      glutamate release was investigated in rat and marmoset striatal synaptosomes.
      Enadoline decreased 4-aminopyridine (2 mM)-stimulated glutamate release (rat:
      IC50 approximately 8.7 microM, marmoset: IC50 approximately 2.9 microM). The
      effect of enadoline was reversed by nor-binaltorphimine (5 microM). These data
      indicate that, in the striatum of the rat and marmoset, kappa-opioid receptor
      agonists can modulate glutamate release. These findings may have implications for
      the treatment of Parkinson's disease.

PMID- 8566107
TI  - In vivo and in vitro effects of muscarinic receptor antagonists on contractions
      and release of [3H]acetylcholine in the rabbit urinary bladder.
AB  - The functional effects of muscarinic receptor antagonists were examined in vivo
      and in vitro on the rabbit urinary bladder. Inhibitory effects on carbachol
      evoked contractions of detrusor strips were pronounced for 4-diphenylacetoxy-N
      methylpiperidine (4-DAMP; -logIC50: 8.64), p-fluoro-hexahydro-sila-diphenidol
      (pFHHSiD; 7.84) and atropine (8.27), while they were less pronounced for
      pirenzepine (6.62) and methoctramine (5.36). 4-DAMP and methoctramine increased
      3H overflow from [3H]choline-labelled strips in response to electrical
      stimulation, contrary to pirenzepine, which decreased the overflow. Concomitant
      contractions were markedly reduced by 4-DAMP and by pirenzepine, but not by
      methoctramine. The -logIC50 estimations for atropine-sensitive electrically
      evoked contractions revealed methoctramine (4.85) to be less potent on nerve
      evoked contractions than on carbachol-evoked contractions, in contrast to
      pirenzepine (7.15) and 4-DAMP (9.15). The effects of the antagonists in
      anaesthetized rabbits resembled those in vitro. Thus, muscarinic receptors in the
      rabbit urinary bladder are heterogeneous; prejunctional facilitatory (M1) and
      inhibitory (M2) for acetylcholine release, and postjunctional muscarinic M3
      receptors mediating contractile responses.

PMID- 8566108
TI  - Methylenedioxymethamphetamine induces opposite changes in central pre- and
      postsynaptic 5-HT1A receptors in rats.
AB  - The present study examined the short- and long-term effects of single and
      repeated administration of 3,4-methylenedioxy-methamphetamine (MDMA, 'ecstasy')
      on somatodendritic and postsynaptic 5-HT1A receptors of the rat brain. [3H]8
      Hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) was used to label 5-HT1A
      receptors in the brain stem region containing the dorsal raphe nucleus and in the
      frontal cortex. As expected, both schedules of treatment reduced the serotonin (5
      hydroxytryptamine, 5-HT) content and [3H]paroxetine binding in the frontal cortex
      but not in the brain stem. Multiple but not single MDMA administration
      significantly reduced 5-HT1A receptor density in the selected brain stem region.
      In the frontal cortex, both MDMA treatments increased or tended to increase 5
      HT1A receptor number, the effect being more marked after repeated drug
      administration.

PMID- 8566109
TI  - Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus
      human PGHS-1.
AB  - The isozymes of prostaglandin G/H synthase (PGHS) are shown to be differentially
      inhibited in vitro by currently marketed nonsteroidal anti-inflammatory drugs
      (NSAIDs) using microsomal rhPGHS-1 and rhPGHS-2. Comparison of selectivity ratios
      (IC50 rhPGHS-1/IC50 rhPGHS-2) demonstrated a 10-fold selectivity of etodolac
      (Lodine) for rhPGHS-2, whereas the other NSAIDs evaluated demonstrated no
      preference or a slight preference for inhibition of rhPGHS-1. In vitro enzyme
      results were supported by a human whole blood assay where etodolac also
      demonstrated a 10-fold selectivity for inhibition of PGHS-2 mediated TxB2
      production. Taken together, these data may be key to explaining the clinically
      observed gastrointestinal safety of etodolac versus other marketed NSAIDs.

PMID- 8566110
TI  - Flumazenil blocks the anxiolytic action of allopregnanolone.
AB  - In the burying behaviour test allopregnanolone (0.5 mg/rat) reduced the
      cumulative time of burying, interpreted as a reduction in anxiety. The selective
      benzodiazepine antagonist, flumazenil (5 and 10 mg/kg), did not affect the
      burying behaviour when administered alone but effectively prevented the reduction
      produced by allopregnanolone. No scheme modified the ambulatory behaviour, thus
      suggesting that the effect of these treatments was selective on experimental
      anxiety. These results indicate that the anxiolytic actions of neurosteroids are
      most likely mediated via the stimulation of GABAA receptors. Data are discussed
      on the basis of such relationships.

PMID- 8566111
TI  - Bradykinin B2 receptor-mediated chronotropic effect of bradykinin in isolated
      guinea pig atria.
AB  - The present study was undertaken to characterize the direct chronotropic effect
      of bradykinin in isolated spontaneously beating atria of the guinea pig.
      Bradykinin caused concentration-dependent increases in the beating rate of atria.
      In contrast, the active metabolite of bradykinin and the typical bradykinin B1
      receptor agonist, Des-Arg9-bradykinin, had no effect on the beating rate of
      atria. Inhibition of converting enzyme or neutral endopeptidase by captopril or
      SQ-28603, respectively, did not affect beating rate but potentiated bradykinin
      induced increase in beating rate. The potent bradykinin B2 receptor antagonist,
      HOE 140, antagonized bradykinin-induced chronotropic effect. In contrast, the
      bradykinin B1 receptor antagonist, Lys-[Leu8]Des-Arg9-bradykinin, had no effect.
      The increase in beating rate caused by bradykinin was not affected by blockade of
      beta 1-adrenoceptors, cyclooxygenase, or nitric oxide synthesis using atenolol,
      indomethacin and N omega-nitro-L-arginine, respectively. Unlike bradykinin,
      angiotensin I and angiotensin II caused very small or no change in beating rate
      in the presence or absence of captopril and SQ-28603. These results indicate that
      bradykinin causes a direct positive chronotropic effect which is mediated by
      activation of bradykinin B2 receptors independently of prostaglandins and beta 1
      adrenoceptors.

PMID- 8566112
TI  - Location of alpha 1-adrenoceptors relative to beta-adrenoceptors in rat
      myocardium.
AB  - Electrically driven rat papillary muscles (1 Hz) were examined for the location
      of their alpha 1-adrenoceptor and beta-adrenoceptor populations relative to each
      other. We determined the horizontal position of the dose-response curves for the
      positive inotropic effects exerted by noradrenaline in the absence and presence
      of the neuronal uptake blocker cocaine and in the absence and presence of the
      beta-adrenoceptor antagonist timolol and of the alpha 1-adrenoceptor antagonist
      prazosin. Cocaine slightly shifted the dose-response curves for alpha 1
      adrenoceptor stimulation to a lower concentration of agonist. In contrast, the
      dose-response curve for beta-adrenoceptor stimulation was markedly shifted by
      cocaine to a lower concentration of agonist. Experiments with corticosterone (an
      extraneuronal uptake blocker) revealed no differential shift of either of the
      dose-response curves. Together, these data indicate that the alpha 1-adrenoceptor
      population is located more distantly from the adrenergic nerve terminals than the
      beta 1-adrenoceptor population in rat myocardium.

PMID- 8566113
TI  - Multiple effects of tyrosine kinase inhibitors on vascular smooth muscle
      contraction.
AB  - The effects of three tyrosine kinase inhibitors: genistein, quercetin and psi
      tectorigenin, were investigated on contractions evoked in de-endothelised rat
      aortic rings, either by phenylephrine or 70 mM K+. A dose-dependent inhibition of
      both contractions by all three compounds was observed, the phenylephrine-mediated
      contractions being more sensitive to genistein. No differences between genistein
      or quercetin effects in pre-treatment or post-treatment protocols were found.
      Ca2+ store refilling, expressed in terms of phenylephrine-induced tension in
      Ca(2+)-free medium, was dose-dependently blocked by quercetin and genistein.
      Sodium orthovanadate, an inhibitor of tyrosine phosphatase, contracted the rat
      aortic rings with an IC50 of 0.66 microM. Its presence during the refilling
      period after exposure to Ca(2+)-free medium completely prevented the subsequent
      response to phenylephrine. One can conclude that the use of the above-mentioned
      protein tyrosine kinase inhibitors in the rat aorta blocks a step involved in
      Ca2+ entry and Ca2+ store refilling. A definite conclusion regarding the vanadate
      effects is not possible due to the fact that this compound also affects Ca2+ ATP
      ases.

PMID- 8566114
TI  - Characterization of [3H]YM060, a potent and selective 5-HT3 receptor radioligand,
      in the cerebral cortex of rats.
AB  - The binding properties of a new radioligand, [methyl-3H]-(-)-(R)-5-[(1-methyl-1H
      indol-3-yl)carbonyl]-4,5,6,7- tetrahydro-1H-benzimidazole monohydrochloride
      ([3H]YM060), were studied in membranes of the rat cerebral cortex. [3H]YM060
      rapidly associated with its binding sites in membranes and reversibly
      dissociated. Saturation analysis revealed that the specific binding of [3H]YM060
      was saturable and non-specific binding was low. Scatchard analysis yielded a
      linear plot, suggesting a single population of binding sites with a dissociation
      constant (Kd) of 8.4 +/- 0.2 pM (n = 3) and the kinetic Kd determined from the
      association constant (K+1) and the dissociation rate constant (K-1) was similar.
      The maximum number of binding sites (Bmax) was 37.0 +/- 0.8 fmol/mg protein (n =
      3). [3H]YM060 binding was potently and stereospecifically inhibited by serotonin
      (5-HT)3 receptor agonists and antagonists. Other 5-HT receptor ligands such as 8
      OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), methysergide and ketanserin
      were inactive to inhibit specific binding at 10(-4) M. These results suggest that
      [3H]YM060 is a highly potent and selective 5-HT3 receptor radioligand and will be
      useful in the further analysis of 5-HT3 receptors.

PMID- 8566115
TI  - Influence of selective alpha 2-adrenergic agents on mustard oil-induced central
      hyperalgesia in rats.
AB  - The effects of systemically administered medetomidine, an alpha 2-adrenoceptor
      agonist, and atipamezole, an alpha 2-adrenoceptor antagonist, on mustard oil
      induced central hyperalgesia were determined in unanesthetized rats. The
      mechanical threshold for eliciting a hindlimb flexion reflex (a nocifensive
      response) was determined with a series of calibrated monofilaments. Under control
      conditions mustard oil produced a significant decrease of the hindlimb withdrawal
      threshold for mechanical stimuli applied to a distal site in the hindlimb,
      whereas the corresponding threshold in the (untreated) contralateral side was not
      changed. Medetomidine administered 12 min prior to mustard oil treatment produced
      a significant dose-dependent (3-30 micrograms/kg s.c.) attenuation of the mustard
      oil-induced threshold decrease whereas the withdrawal threshold of the
      contralateral (untreated) hindlimb was not changed at these low doses. The
      antinociceptive effect of medetomidine (10 micrograms/kg) administered 12 min
      prior to the mustard oil treatment was not significantly stronger than the effect
      of medetomidine administered immediately after the mustard oil treatment.
      Atipamezole at a high (1000 micrograms/kg) or a low (10 micrograms/kg) dose did
      not influence the mustard oil-induced threshold decrease, whereas at an
      intermediate dose (100 micrograms/kg) atipamezole alone had a significant
      antinociceptive effect on mustard oil-induced hyperalgesia. The results indicate
      that medetomidine produces a selective attenuation of central hyperalgesia at
      doses which are sub-antinociceptive in intact rats. A pre-emptive treatment with
      medetomidine did not produce stronger antinociception than medetomidine treatment
      after the development of hyperalgesia. An alpha 2-adrenoceptor antagonist,
      atipamezole, attenuated central hyperalgesia in a non-monotonic fashion.

PMID- 8566116
TI  - Pharmacological characterization of GR82334, a tachykinin NK1 receptor
      antagonist, in the isolated spinal cord of the neonatal rat.
AB  - Pharmacological characteristics of [D-Pro9,[spiro-gamma
      lactam]Leu10,Trp11]physalaemin-(1-11) (GR82334), a tachykinin NK1 receptor
      antagonist, and its effects on slow depolarizing responses of lumbar ventral
      roots evoked by primary afferent stimulation were examined in isolated spinal
      cord preparations of neonatal rats. GR82334 (1-3 microM) caused dose-dependent
      rightward shifts of the concentration-response curves for substance P, substance
      P methyl ester, delta-aminovaleryl [Pro9,N-Me-Leu10]substance P-(7-11) (GR73632)
      and neurokinin A in normal artificial cerebrospinal fluid and those for substance
      P methyl ester, GR73632 and neurokinin A in the presence of tetrodotoxin. GR82334
      (10 microM) did not evoke gamma-aminobutyric acid (GABA) release from spinal
      cords of neonatal rats, whereas [D-Pro9,[spiro-gamma-lactam]
      Leu10,Trp11]substance P (GR71251), another tachykinin NK1 receptor antagonist,
      induced a significant increase in GABA release. GR82334 (1-3 microM) markedly
      depressed the slow depolarizing response of ventral roots, referred to as slow
      ventral root potential, evoked by the stimulation of the contralateral dorsal
      root or the ipsilateral saphenous nerve. In contrast,
      cyclo[Gln,Trp,Phe,Gly,Leu,Met] (L-659,877, 1 microM), a selective tachykinin NK2
      receptor antagonist, did not depress the saphenous nerve-evoked slow ventral root
      potential and did not antagonize the action of neurokinin A to induce ventral
      root depolarization. The present results provide further evidence for the
      involvement of substance P, neurokinin A and tachykinin NK1 receptors in the
      primary afferent-evoked slow ventral root potentials.

PMID- 8566117
TI  - L-alpha-aminoadipic acid as a regulator of kynurenic acid production in the
      hippocampus: a microdialysis study in freely moving rats.
AB  - L-alpha-Aminoadipic acid is a lysine metabolite with neuroexcitatory properties,
      and has previously been shown to inhibit the production of the broad spectrum
      excitatory amino acid receptor antagonist kynurenic acid in brain tissue slices.
      The effects of L-alpha-aminoadipic acid on the levels of extracellular kynurenic
      acid were now studied by microdialysis in the dorsal hippocampus of freely moving
      rats. Application of L-alpha-aminoadipic acid through the microdialysis probe
      dose dependently decreased both the concentration of endogenous kynurenic acid
      and of kynurenic acid which was produced de novo from its bioprecursor L
      kynurenine (500 microM applied through the probe). 500 microM L-alpha-aminoadipic
      acid lowered the kynurenic acid concentration in the dialysate by 47% and 28%
      with and without precursor loading, respectively, whereas D-alpha-aminoadipic
      acid was without effect. Co-administration of 500 microM L-alpha-aminoadipic acid
      with 50 microM veratridine, which by itself produces a substantial decrease in
      the levels of extracellular kynurenic acid, did not result in a further reduction
      in kynurenic acid concentrations. Extensive neuronal degeneration caused by an
      intrahippocampal injection of quinolinic acid (120 nmol) did not interfere with
      the effect of L-alpha-aminoadipic acid. Taken together, these data suggest that
      the effect of L-alpha-aminoadipic acid on extracellular kynurenic acid levels is
      likely due to its direct action on astrocytes, which are known to harbor
      kynurenic acid's biosynthetic enzyme, kynurenine aminotransferase. L-alpha
      Aminoadipic acid may modulate kynurenic acid function in the brain and thus play
      a role in the pathogenesis of neurodegenerative and seizure disorders.

PMID- 8566118
TI  - Effects of the non-peptide inhibitor OPC-21268 on oxytocin and vasopressin
      stimulation of rat and human myometrium.
AB  - OPC-21268 (1-[-1-[4-(3-acetylaminopropoxy)benzoyl]-piperidyl]-3,4- dihydro-2(1H)
      quinolinone), a non-peptide vasopressin V1 receptor antagonist, inhibited
      oxytocin- and vasopressin-induced contractions of myometrial strips from rats and
      from full-term pregnant women. Administered intravenously in rats the drug also
      inhibited uterine contractions caused by infusion of oxytocin. When incubated
      with purified plasma membranes from rat or human myometrial tissue, OPC-21268
      inhibited the specific receptor binding of tritiated oxytocin and vasopressin in
      a dose-dependent and reversible way.

PMID- 8566119
TI  - Effect of rolipram in a murine model of acute inflammation: comparison with the
      corticoid dexamethasone.
AB  - Treatment of mice with rolipram, a phosphodiesterase type 4 inhibitor,
      selectively modified the acute inflammatory reaction elicited by zymosan
      administration in 6-day-old mouse air-pouches. Rolipram (1-10 mg kg-1, i.p.)
      prevented the rise of endogenous tumor necrosis factor-alpha (TNF-alpha) in the
      lavage fluids (approximately 60% inhibition) induced by zymosan, with no effect
      upon interleukin-1 alpha levels. This action was not accompanied by changes in
      neutrophil accumulation, but the amount of elastase released in the lavage fluids
      was significantly reduced (approximately 50%). Dexamethasone (1.5 mg kg-1, i.v.),
      used for comparative purposes, significantly reduced the release of TNF-alpha (>
      50%), interleukin-1 alpha (> 70%) and cellular infiltration (approximately 50%),
      but had only a marginal effect on the release of elastase activity. In
      conclusion, in this murine model of acute inflammation induced by zymosan,
      rolipram inhibited the endogenous TNF-alpha production at a local site of
      inflammation, such as the subcutaneous air-pouch, and prevented the full
      activation of migrated cells.

PMID- 8566120
TI  - Simultaneous measurement of plasma protein extravasation and carotid vascular
      resistance in the rat.
AB  - Stimulation of the right trigeminal ganglion in pentobarbital anaesthetised rats
      increased mean arterial blood pressure and decreased right carotid vascular
      resistance but had no effect on left carotid vascular resistance. Sumatriptan
      (0.3 mg/kg i.v.) pretreatment did not significantly affect basal levels or
      stimulation induced changes in blood pressure or carotid vascular resistance.
      Trigeminal stimulation produced plasma protein extravasation (measured using a
      fluorescent marker) into the dura mater on the ipsilateral side which was
      significantly reduced by sumatriptan. These studies show that sumatriptan can
      reduce plasma protein extravasation while having no measurable effect on total
      carotid blood flow.

PMID- 8566121
TI  - A pharmacological profile of the selective silent 5-HT1A receptor antagonist, WAY
      100635.
AB  - WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-
      pyridinyl)cyclohexanecarboxamide trihydrochloride) is an achiral phenylpiperazine
      derivative that binds with high affinity and selectivity to the 5-HT1A receptor.
      WAY-100635 displaced specific binding of the 5-HT1A radioligand, [3H]8-OH-DPAT (8
      hydroxy-2-(di-n-propylamino)tetralin), to rat hippocampal membranes with a pIC50
      of 8.87. This represented a greater than 100-fold selectivity relative to binding
      at other 5-HT receptor subtypes and major neurotransmitter receptor, reuptake and
      ion channel sites. In functional assays, WAY-100635 was a potent 5-HT1A receptor
      antagonist, with no evidence of any 5-HT1A receptor agonist or partial agonist
      activity. In the isolated guinea-pig ileum WAY-100635 was a potent and, at high
      concentrations, an insurmountable antagonist of the 5-HT1A receptor agonist
      action of 5-carboxamidotryptamine, with an apparent pA2 value (at 0.3 nM) of
      9.71. WAY-100635 blocked the inhibitory action of 8-OH-DPAT on dorsal raphe
      neuronal firing in the anaesthetised rat at doses which had no inhibitory action
      per se. In behavioural models, WAY-100635 itself induced no overt behavioural
      changes but potently antagonised the behavioural syndrome induced by 8-OH-DPAT in
      the rat and guinea-pig (minimum effective dose = 0.003 mg/kg s.c. and ID50 = 0.01
      mg/kg s.c., respectively). WAY-100635 also blocked the hypothermia induced by 8
      OH-DPAT in the mouse and rat with ID50 values of 0.01 mg/kg s.c. These data
      indicate that WAY-100635 will be used as a standard antagonist in further studies
      of 5-HT1A receptor function.

PMID- 8566122
TI  - Effects of liposome-entrapped platelet-activating factor in the isolated rat
      trachea.
AB  - The effects of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3
      phosphocholine)-filled liposomes upon rat tracheal rings in vitro were examined.
      The capture of liposomes by the smooth muscle cells of the isolated tracheal
      rings as well as the release of their content into the cytoplasm was shown by
      using Evans blue (5 x 10(-4) M)-loaded liposomes. Administration of PAF (10(-3)
      M)-filled liposomes contracted the preparations, in contrast with extracellular
      administration of PAF and control liposomes, which had no effect. Administration
      during the plateau or pretreatment with liposomes containing BN 52021 (3-t
      butylhexahydro-4,7b-trihydroxy-8-methyl-9H-1,7a-epoxymethano- 1H,6aH-
      cyclopenta[c]furo(2,3-b)furo[3',2':3,4]cyclopental [1,2-d]furan-5,9,12(4H)
      trione) ((10(-3) M, a selective PAF receptor antagonist) or heparin (5 x 10(-5)
      M) blocked this contraction. BN 52021 and heparin, not entrapped in liposomes,
      had no such effect. Our data suggest an intervention of PAF in the mechanisms of
      contraction of tracheal smooth muscle, involving a direct or indirect
      intervention (intracellular receptors for PAF cannot be excluded). At the same
      time, the rat trachea contraction induced by PAF-loaded liposomes could be linked
      to the PtdIns(1,4,5)P3-dependent Ca2+ channels from the endoplasmic reticulum
      and/or to the interaction with G proteins, as shown by the blocking effects of
      heparin-containing liposomes.

PMID- 8566123
TI  - Differential vasodilatory action of 2-octynyladenosine (YT-146), an adenosine A2
      receptor agonist, in the isolated rat femoral artery and vein.
AB  - The vasodilatory action of 2-octynyladenosine (YT-146), an adenosine A2 receptor
      agonist, was investigated in the isolated rat femoral artery and vein. Exposure
      to YT-146 resulted in preferential vasodilatation; the vein was completely
      dilated at YT-146 concentrations as low as 10(-7) M; in contrast, a concentration
      of YT-146 greater than 10(-4) M was necessary to induce complete relaxation in
      the femoral artery. 2-[p-(2-Carboxyethyl)-phenethylamine]-5'-N
      ethylcarboxamidoadenosine (CGS 21680) also evoked stronger dilation in the vein
      than in the artery. The vasodilatory action of N6-cyclopentyladenosine (CPA) was
      much weaker in the vein than that of YT-146. YT-146-induced vasodilation in the
      artery was antagonized by neither 10(-7) M 1,3-dipropyl-8-cyclopentylxanthine
      (DPCPX) nor 3 x 10(-6) M (E)-8-(3,4-dimethoxystylyl)-1,3-dipropyl-7
      methylxanthine (KF17837), while the vasodilation in the vein was only antagonized
      by KF17837, suggesting that the vasodilation may involve adenosine A2 receptor
      activation in the vein. However, the present study did not provide evidence of a
      link between adenosine agonist-induced vasodilation and adenosine A2 receptor
      activation in the artery. The addition of 10(-4) M N omega-nitro-L-arginine
      partially reversed YT-146-induced vasodilation in the artery, but not in the
      vein. The reversal of YT-146-induced vasodilation by N omega-nitro-L-arginine in
      the artery was attenuated by the addition of 10(-3) M L-arginine. Removal of the
      endothelium decreased YT-146-induced vasodilation in the artery, but not in the
      vein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8566124
TI  - [3H]propyl-6-azido-beta-carboline-3-carboxylate: a new photoaffinity label for
      the GABAA-benzodiazepine receptor.
AB  - [3H]Propyl-6-azido-beta-carboline-3-carboxylate ([3H]ACCP) exhibited a high
      affinity for GABAA receptors affinity purified from the brains of adult rats, and
      binding of this compound could be inhibited by several ligands of the
      benzodiazepine binding site of GABAA receptors. On irradiation with UV light,
      [3H]ACCP, similarly to [3H]flunitrazepam, irreversibly labeled a protein with an
      apparent molecular weight of 51 kDa in affinity-purified GABAA receptors, and
      this labeling could be inhibited in the presence of diazepam. These data indicate
      that [3H]ACCP can be used as a photoaffinity label for GABAA receptors.

PMID- 8566125
TI  - Inhibition of interleukin-1 beta-induced pyresis in the rabbit by peptide 204-212
      of lipocortin 5.
AB  - The intracerebroventricular administration of interleukin-1 beta (12.5 ng/kg) in
      rabbits caused a prompt rise of prostaglandin E2 concentration (+ 632.6 +/-
      243.9%) in the cerebrospinal fluid followed by hyperthermia (+ 1.61 +/- 0.14
      delta degrees C). The intracerebroventricular administration of an anti
      inflammatory nonapeptide (amino acids 204-212, SHLRKVFDK) derived from lipocortin
      5, thereafter referred to as lipocortin 5-(204-212)-peptide, inhibited in a
      significant manner both the increase in cerebrospinal fluid [prostaglandin E2]
      and the febrile response induced by the cytokine. This inhibitory effect is
      probably due to interference by the peptide with phospholipase A2 activity. A
      control peptide (FKRVHDLKS) formed by the same amino acids in a randomly shuffled
      sequence had no effect. These results show that, in addition to the anti
      inflammatory effect previously reported, the peptide 204-212 of lipocortin 5
      possesses, like glucocorticoids, anti-pyretic activity. The research on
      lipocortin-derived peptides may lead to the development of novel anti
      inflammatory and anti-pyretic compounds.

PMID- 8566126
TI  - Leukotrienes mediate tracheal hyperresponsiveness after nitric oxide synthesis
      inhibition.
AB  - Preincubation of guinea pig tracheas with the nitric oxide synthase inhibitor, N
      omega-nitro-L-arginine methyl ester (L-NAME, 120 microM) resulted in a
      significant upward shift of the histamine concentration-response curve with a
      concomitant inhibition of prostaglandin E2 production. Preincubation of the
      preparations with a 5-lipoxygenase inhibitor (AA-861, 2-(12-hydroxy-5,10
      dodecadiynyl)-3,5,6-trimethyl-p-benzoquinone) or a leukotriene C4,D4,E4 receptor
      antagonist (FPL 55712, sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy
      propoxy]-4-oxo-8- propyl-4H-1-benzopyran-2-carboxylate) totally blocked the L
      NAME-induced tracheal hyperresponsiveness. A shift from cyclo-oxygenase to
      lipoxygenase products, in particular leukotrienes, is likely to be responsible
      for the L-NAME-induced tracheal hyperresponsiveness.

PMID- 8566127
TI  - Effect of chronic nitric oxide synthesis inhibition on the inflammatory responses
      induced by carrageenin in rats.
AB  - The effect of chronic inhibition of nitric oxide (NO) biosynthesis has been
      investigated in two models of acute inflammation induced by carrageenin, i.e.,
      paw oedema and pleurisy. Chronic inhibition of NO biosynthesis was achieved by
      including N omega-nitro-L-arginine methyl ester (L-NAME) in the drinking water to
      give a dose of approximately 75 mumol/rat/day for 2 and 4 weeks. Control animals
      received either tap water alone or the inactive enantiomer D-NAME. Since chronic
      NO inhibition increases blood pressure, rats made hypertensive (2 kidney-1 clip
      model; 2K-1C) were used to evaluate the effect of hypertension on the carrageenin
      induced paw oedema. In a separate set of experiments, L-NAME-treated animals
      concomitantly received captopril (140 mumol/rat/day) to prevent hypertension.
      Animals chronically treated with L-NAME (but not D-NAME) for 2 and 4 weeks
      developed hypertension to the same extent as 2K-1C rats. Carrageenin-induced paw
      oedema was significantly reduced in animals chronically treated with L-NAME, but
      not with D-NAME or in 2K-1C rats. Subplantar injection of iloprost completely
      reversed the inhibition of paw oedema caused by L-NAME. Captopril (140
      mumol/rat/day) significantly lowered the high blood pressure levels induced by L
      NAME but did not significantly affect the inhibition of paw oedema caused by L
      NAME. No changes in vascular permeability, as assessed by Evans blue
      extravasation, were observed in L-NAME-treated animals. The chronic treatment
      with L-NAME for 2 and 4 weeks did not inhibit carrageenin-induced leucocyte
      migration and fluid exudation into the pleural cavity. Although carrageenin
      induced paw oedema is reduced in L-NAME-treated rats, this response reflects a
      decrease in local blood flow rather than an effect on vascular permeability.

PMID- 8566128
TI  - Comparative study of elgodipine and nisoldipine on the contractile responses of
      various isolated blood vessels.
AB  - The effects of elgodipine, a new dihydropyridine derivative, were compared to
      those of nisoldipine on contractile responses in various isolated artery rings
      and on mechanical activity in portal vein segments. Arteries used were: rabbit
      aorta, mesenteric (fifth branch), femoral and basilar, and sheep coronary
      arteries. Elgodipine and nisoldipine (10(-16)-3 x 10(-6) M) produced a
      concentration-dependent inhibition of the contractile responses induced by high
      K+ (80 mM), 5-hydroxytryptamine (10(-5) M) or noradrenaline (10(-6) M or 10(-4)
      M) in all the arteries studied. The inhibitory effect of elgodipine was greater
      in mesenteric resistance vessels (IC50 = 8.0 +/- 2.1 x 10(-12) M and 2.0 +/- 0.5
      x 10(-13) M for the depression of high K(+)- and agonist-induced contraction,
      respectively), and in coronary arteries (IC50 = 2.6 +/- 0.3 x 10(-10) M and 9.0
      +/- 1.4 x 10(-8) M for the inhibition of high K(+)- and agonist-induced
      contraction, respectively). In addition, the action of elgodipine in peripheral
      resistance vessels and in the coronary artery was more prominent than in aorta or
      femoral arteries, and this tissue selectivity was more apparent for elgodipine
      than for nisoldipine. In rat portal vein elgodipine (IC50 = 6.5 +/- 0.9 x 10(-8)
      M) and nisoldipine (IC50 = 8.5 +/- 1.3 x 10(-8) M) reduced in a concentration
      dependent manner the development of mechanical activity. Furthermore, contractile
      responses produced by the addition of Ca2+ (1-5 mM) to Ca(2+)-free high K+
      solution were also concentration dependently inhibited by elgodipine. However,
      elgodipine did not modify noradrenaline-induced contractions attributed to
      intracellular Ca2+ release. The results of this study indicate that elgodipine
      has potent vasodilator properties and vascular selectivity. The mechanisms
      through which elgodipine relaxes vascular smooth fibres seem to be related to its
      ability to inhibit the entry of extracellular Ca2+ into the cell.

PMID- 8566129
TI  - Metabotropic and ionotropic glutamate receptors mediate opposite effects on
      periaqueductal gray matter.
AB  - Microinjections, into the dorso-lateral periaqueductal gray matter, of N-methyl-D
      aspartic acid (NMDA, 0.07-7 nmol/rat) significantly (P < 0.01) increased arterial
      blood pressure in a dose-related manner. Pretreatment, 5 min before NMDA (7
      nmol/rat), in the same area with 2-amino-5-phosphonovaleric acid (2-APV, 5
      nmol/rat), a selective antagonist of NMDA receptors, significantly (P < 0.01)
      reduced NMDA-induced arterial hypertension. trans-(+/-)-1-Amino-1,3
      cyclopentanedicarboxylic acid (t-ACPD, 6-30 nmol/rat), an agonist of metabotropic
      glutamate receptors (mGlu receptors), significantly (P < 0.01) decreased arterial
      blood pressure when microinjected into the dorsal-lateral periaqueductal gray
      matter. Pretreatment, 5 min before t-ACPD (30 nmol/rat), in the same area with L
      2-amino-3-phosphono-propionate (L-AP-3, 30 nmol/rat), a putative antagonist of
      the mGlu receptors, was not able to prevent t-ACPD-induced hypotension.
      Microinjections of L-AP-3 (30 nmol/rat) induced a hypotension similar to the one
      obtained with t-ACPD at the dose of 6 nmol/rat. From these data we can suggest
      that mGlu receptors act inversely to the NMDA receptors in the dorso-lateral
      periaqueductal gray area and that L-AP-3 is a partial agonist rather than an
      antagonist of mGlu receptors within the periaqueductal gray area.

PMID- 8566130
TI  - Discrepancies in characterization of sigma sites in the mouse central nervous
      system.
AB  - The characteristics of [3H](+)-pentazocine and [3H]1,3-di(2-tolyl) guanidine
      (DTG) binding to mouse whole brain, cortex, cerebellum and spinal cord membranes
      were investigated in radioreceptor assays. [3H](+)-Pentazocine bound to a single,
      high affinity site (Kd = 1.2-1.6 nM) with increasing density along the neuraxis
      from the cortex (Bmax = 543 fmol/mg protein) to the spinal cord (Bmax = 886
      fmol/mg protein). Hot saturation studies resolved the presence of one binding
      site for [3H]DTG showing no tissue variations in terms of density (Bmax = 1075
      1264 fmol/mg protein) or affinity (Kd = 16.6-22.3 nM). Incubation with 100 nM (+)
      pentazocine revealed two classes of high affinity [3H]DTG labeled binding sites
      corresponding to sigma 1 and sigma 2 subtypes. A preponderance of sigma 2 sites
      was revealed in all investigated tissues. Different pharmacological profiles were
      demonstrated for the sigma 2 sites in mouse whole bain compared to mouse spinal
      cord. However, competition studies indicated that the whole brain and spinal
      [3H](+)-pentazocine labeled sigma 1 binding sites exhibited similar
      pharmacological properties. The density of [3H](+)-pentazocine labeled sigma 1
      population was found not to match that of [3H]DTG labeled sigma 1 site throughout
      the mouse central nervous system. The presence of low affinity [3H]DTG labeled
      sites was demonstrated in cold saturation experiments. Equilibrium binding data
      for the low affinity [3H]DTG binding site resulted in an increasing density (Bmax
      = 1973-11,369 fmol/mg protein) with a decreasing affinity (Kd = 242-943 nM) in
      mouse cortex through the spinal cord.

PMID- 8566131
TI  - Characterization of the interaction of zamifenacin at muscarinic receptors in
      vitro.
AB  - The interaction of zamifenacin ((3R)-(+)-diphenylmethoxy-1-(3,4)
      methylenedioxyphenethyl)pi peridine) at muscarinic receptor subtypes was studied
      using radioligand binding and functional techniques, in vitro. In radioligand
      binding studies, zamifenacin acted as a competitive antagonist, with the
      following pKi values; rat cerebral cortex (M1) 7.90 +/- 0.08, myocardium (M2)
      7.93 +/- 0.13, submaxillary gland (M3) 8.52 +/- 0.04 and rabbit lung (M4) 7.78 +/
      0.04. In functional studies zamifenacin acted as a surmountable antagonist,
      exhibiting the following apparent affinity values; canine saphenous vein
      (putative M1) 7.93 +/- 0.09, guinea-pig left atria (M2) 6.60 +/- 0.04, guinea-pig
      ileum (M3) 9.31 +/- 0.06, guinea-pig oesophageal muscularis mucosae (M3) 8.84 +/-
      0.04, guinea-pig trachea (M3) 8.16 +/- 0.04, and guinea-pig urinary bladder (M3)
      7.57 +/- 0.15. Therefore, zamifenacin is selective for muscarinic M3 receptors in
      guinea-pig ileum, oesophageal muscularis mucosae, trachea and bladder over
      muscarinic M2 receptors in atria. The degree of muscarinic M3/M2 receptor
      selectivity depends upon the muscarinic M3 receptor preparation studied.

PMID- 8566132
TI  - Effect of stress and cyclosporine on ornithine decarboxylase activity in rat
      submaxillary lymph nodes.
AB  - This study was performed: (1) to assess whether the stress produced in rats by
      daily turpentine oil injections for 5 days, or by restraining the animals for 30
      min during 5 days, affected basal and Freund's adjuvant-stimulated submaxillary
      lymph node ornithine decarboxylase activity, an indicator of cell proliferation;
      (2) to analyze whether the activity of the immunosuppressive drug cyclosporine on
      submaxillary lymph node ornithine decarboxylase activation after Freund's
      adjuvant injection was modified in stressed rats; (3) to examine the mediation of
      stress effects on submaxillary lymph node ornithine decarboxylase activation by
      regional sympathetic or parasympathetic nerves. Animals subjected to a unilateral
      superior cervical ganglionectomy, or to a unilateral chorda tympani section,
      together with a contralateral sham-operation were employed. After turpentine oil
      or restraint stress, a significant decrease in submaxillary lymph node ornithine
      decarboxylase was found. A unilateral sympathetic denervation of submaxillary
      lymph nodes counteracted in part the inhibitory effect of stress on ornithine
      decarboxylase activation, as well as augmented the enzyme response in innervated
      submaxillary lymph nodes. Ornithine decarboxylase activation attained similar
      values in parasympathetic decentralized or intact submaxillary lymph nodes and
      the unilateral parasympathetic decentralization did not interfere with the
      inhibition of enzyme activity found in turpentine oil-stressed rats. Cyclosporine
      administration (5 or 20 mg/kg) significantly decreased Freund's adjuvant-induced
      ornithine decarboxylase activity in the submaxillary lymph nodes of control rats,
      but failed to modify it in turpentine oil-stressed animals. In this latter group,
      a higher (40 mg/kg) dose of cyclosporine decreased ornithine decarboxylase
      activity on the innervated side only. A diminished inhibitory response to
      cyclosporine was found in the parasympathetic decentralized submaxillary lymph
      nodes of unstressed rats. The results support the view that the immunosuppressive
      effects of cyclosporine may diminish during stress, in part due to changes in the
      traffic of neural signals in local sympathetic nerves.

PMID- 8566133
TI  - Effects of the isoprostane, 8-epi-prostaglandin F2 alpha, on the contractility of
      the human myometrium in vitro.
AB  - 8-epi-prostaglandin F2 alpha stimulated contraction of human myometrial strips
      obtained from five different donors at the time of hysterectomy with a pEC50
      value of 6.3 +/- 0.5. In paired strips from the same donors the pEC50 value for
      the selective TP receptor agonist U46619 ([1R-[1a,4a,5b(Z),6a(1E,3S*)]]-7-[6-(3-
      hydroxy-1-octenyl)-2-oxabicyclo[2.2.1]hept-5-yl]-5-heptenoic acid) was 8.3 +/-
      0.4. In strips from four other donors 8-epi-prostaglandin F2 alpha was
      ineffective whereas the pEC50 for U46619 was 6.9 +/- 0.3. Responses to 8-epi
      prostaglandin F2 alpha were unaffected by the selective DP receptor antagonist BW
      A868C (3-benzyl-5-(6-carboxyhexyl)-1-(2- cyclohexyl-2
      hydroxyethylamino)hydantoin) at 50 nM but were blocked by the selective TP
      receptor antagonist L670596 ((-)6,8-difluoro-9-p-methylsulfonyl benzyl-1,2,3,4-
      tetrahydrocarbazol-1-yl-acetic acid) at 50 nM. The pIC50 values obtained when the
      TP receptor antagonists GR 32191 ([1R- [1 alpha(Z),2 beta,3 beta,5 alpha]]-(+)-7
      [5-[[(1,1'-biphenyl)-4- yl]methoxy]-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4
      heptenoic acid), ICI D1542 ((4(Z)-6-[(2S,4S,5R)-2-[1-methyl-1-(2-nitro-4
      tolyloxy)ethyl]- 4-(3-pyridyl)-1,3-dioxan-5-yl]hex-4-enoic acid), ICI 192605
      (4(Z)-6-[(2,4,5-cis)-2-(2-chlorophenyl)-4-(2-hydroxyphenyl)-1,3- dioxan-5
      yl]hexenoic acid), L670596 and SQ 29548 ([1S-(1 alpha,2 beta(5Z),3 beta,4 alpha]]
      7- [3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7- oxabicyclo[2.2.1]hept-2-yl]
      5-heptenoic acid) were added cumulatively to strips pre-contracted with an EC80
      concentration of 8-epi-prostaglandin F2 alpha were not significantly different
      from those obtained when an EC80 concentration of U46619 was used. The effects of
      8-epi-prostaglandin F2 alpha on strips pre-contracted with an EC80 concentration
      of U46619 were not different from those of U46619 itself. It is concluded that in
      the non-pregnant human myometrium 8-epi-prostaglandin F2 alpha is a medium
      potency contractile agonist acting predominantly at the TP receptor.

PMID- 8566134
TI  - Endogenous serotonin modulates histamine release in the rat hypothalamus as
      measured by in vivo microdialysis.
AB  - In vivo microdialysis was used to study the effects of serotonergic drugs on
      histamine release from the suprachiasmatic nuclei region of the anterior
      hypothalamus in anesthetized rats. Local perfusion with serotonin (5
      hydroxytryptamine, 5-HT) increased histamine release significantly and dose
      dependently. Methysergide (10 mg/kg i.p.), a 5-HT2C/2A receptor antagonist, given
      30 min before 5-HT perfusion, blocked the 5-HT-evoked histamine release.
      Methysergide (10 mg/kg i.p.), given alone, also suppressed basal histamine
      release by 33%. Dexfenfluramine (10 microM), a 5-HT releaser and uptake blocker,
      administered via the microdialysis probe, significantly enhanced hypothalamic
      histamine release. With the same dose of dexfenfluramine, 5-HT release increased
      10-fold in the same brain area. These results show for the first time that
      endogenous 5-HT modulates histamine release in vivo and it has a tonic
      stimulatory effect on the histaminergic nerve terminals of the rat anterior
      hypothalamus.

PMID- 8566135
TI  - Contractions and relaxations accompanied by endothelial nitric oxide production
      induced in the porcine coronary artery by Ca2+, Ba2+ and Sr2+.
AB  - In order to investigate the effects of Ca2+, Ba2+ and Sr2+ on vascular
      endothelial nitric oxide (NO) production, contractile and relaxant responses of
      porcine depolarized coronary arteries to these divalent cations were compared. In
      the presence of diltiazem, Ba2+ induced NO-dependent relaxation, Sr2+ did
      slightly and Ca2+ did not; however all three cations increased cGMP levels in
      endothelium-intact arteries to similar extents. In the absence of diltiazem,
      these cations evoked contractions: the EC50 of Ca2+ for endothelium-denuded
      arteries was lower than those of Ba2+ and Sr2+. The IC50 of diltiazem for
      arteries precontracted with Ca2+ was higher than for arteries precontracted with
      Ba2+ and Sr2+. These results suggest that Ba2+ and Sr2+, as well as Ca2+,
      activate coronary arterial NO production, and also that the different responses
      of coronary arteries to these divalent cations can be explained, in part, by the
      different sensitivities of the smooth muscle to these cations and by the
      different potencies of diltiazem to inhibit the contractions the cations induced.

PMID- 8566136
TI  - Vasorelaxant effect of PACAP-27 on canine cerebral arteries and rat intracerebral
      arterioles.
AB  - The vasorelaxant effects of pituitary adenylate cyclase activating polypeptide
      (PACAP)-27 were examined and compared with those of PACAP-38 and vasoactive
      intestinal polypeptide (VIP) on isolated canine cerebral arteries and rat
      intracerebral arterioles in vitro. The addition of PACAP-27, PACAP-38 or VIP
      resulted in similar concentration-dependent relaxations in both canine basilar
      arteries and rat intracerebral arterioles. There were regional differences in the
      PACAP-27-induced relaxations measured in canine cerebral arteries. The maximum
      relaxation induced by PACAP-27 was significantly lower in the basilar arteries
      (23.0 +/- 5.6%) than in the rostrally located arteries (proximal middle cerebral
      arteries: 45.4 +/- 5.7%, anterior cerebral arteries: 55.2 +/- 5.8%). The maximum
      relaxation induced by PACAP-27 in the basilar arteries was significantly enhanced
      by mechanical removal of the endothelium (16.4 +/- 4.5% vs. 32.7 +/- 5.8%) as
      well as by pretreatment with indomethacin or aspirin (12.9 +/- 4.1% vs. 48.7 +/-
      6.1% and 46.5 +/- 9.2%, respectively). Incubation of canine cerebral arteries
      with PACAP-27 in vitro resulted in an increased release of prostaglandin F2 alpha
      in the buffer from 14.5 +/- 2.1 pg/min/1 mg vessel to 31.1 +/- 4.2 pg/min/1 mg
      vessel, while other cyclooxygenase cascade metabolites such as prostaglandin E2,
      thromboxane B2 and 6-keto prostaglandin F1 alpha did not change. These data
      suggest that the PACAP-27-induced relaxation of canine basilar arteries may be
      associated with prostaglandin F2 alpha or its precursor, prostaglandin H2.

PMID- 8566137
TI  - Pharmacology of CS-866, a novel nonpeptide angiotensin II receptor antagonist.
AB  - CS-866, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy-4-(1-hydroxy-1- methylethyl)-2
      propyl-1-(4-[2-(tetrazol-5-yl)-phenyl]phenyl)met hylimidazol- 5-carboxylate, a
      prodrug type angiotensin receptor antagonist, is deesterified to the active acid,
      RNH-6270. RNH-6270 inhibited [125I]angiotensin II binding to bovine adrenal
      cortical membranes (angiotensin AT1 receptors) with an IC50 value of 7.7 nM, but
      not [125I]angiotensin II binding to bovine cerebellar membranes (angiotensin AT2
      receptors), indicating the selectivity of the compound for angiotensin AT1
      receptors. In guinea pig aortas, RNH-6270 reduced the maximal response of the
      concentration-contractile curve for angiotensin II (pD'2 = 9.9), but had no
      effect on the contractile response induced by phenylephrine or KCl. In conscious
      rats, intravenously injected RNH-6270 inhibited angiotensin II-induced pressor
      responses in a dose-dependent manner, and orally administered CS-866 produced a
      long-lasting inhibition of angiotensin II pressor responses. SK&F-525A, a P-450
      inhibitor, suppressed the angiotensin II inhibitory effect of losartan, but not
      that of CS-866. These results demonstrate that RNH-6270 is a potent and AT1
      selective angiotensin receptor antagonist and that, after oral administration, CS
      866 has a long-lasting angiotensin II inhibitory action which is not affected by
      drug metabolizing enzymes in the liver.

PMID- 8566138
TI  - Different effects of two aldose reductase inhibitors on nociception and
      prostaglandin E.
AB  - This study examined the effect of two structurally dissimilar aldose reductase
      inhibitors, N-[[5-(trifluoromethyl)-6-methoxy-1- napthalenyl]thioxomethyl]-N
      methlyglycine (tolrestat) and 4-amino-2,6-dimethylphenyl-sulphonyl nitromethane
      (ICI 222155), on formalin-evoked behavioural responses in control and diabetic
      rats and on capsaicin-evoked release of prostaglandin E from spinal cord slices
      in vitro. Both compounds, given orally for 4 weeks, prevented hyperalgesia in
      diabetic rats 5-20 min after hindpaw formalin injection. ICI 222155 also
      prevented hyperalgesia in diabetic rats 21-60 min after formalin, whereas
      tolrestat suppressed activity in diabetic rats below controls and also suppressed
      activity in controls when given orally or intrathecally. Capsaicin-evoked release
      of prostaglandin E from spinal cord slices of control rats was significantly
      reduced by tolrestat, but not ICI 222155. These data suggest that hyperalgesia in
      diabetic rats is related to glucose metabolism by aldose reductase, whereas
      tolrestat has specific effects on formalin-evoked nociception associated with an
      ability to reduce spinal prostaglandin release.

PMID- 8566139
TI  - [Arg8]vasopressin-induced responses of the human isolated coronary artery:
      effects of non-peptide receptor antagonists.
AB  - Contractions induced by [Arg8]vasopressin (vasopressin) and the effect of
      nonpeptide vasopressin receptor antagonists were studied in the human isolated
      coronary artery. Vasopressin induced contraction of coronary artery segments with
      a high pD2 (9.25) but a low Emax (11.8% of the response to 100 mM K+). This
      response was not affected by removal of the endothelium. Contraction was
      antagonized by the vasopressin V1 receptor antagonist SR 49059 ((2S) 1-[(2R 3S)-5
      chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene- sulfonyl)-3-hydroxy-2,3
      dihydro-1H-indole-2-carbonyl]-pyrrolidine-2- carboxamide) (pA2: 9.76). OPC-31260
      ([5-dimethylamino-1-(4-(2-methylbenzoylamino)benzoyl)-2,3,4,5-tetr ahydro-1H-
      benzazepine]: vasopressin V2 receptor antagonist) and OPC-21268 (1-(1-[4-(3
      acetylaminopropoxy) benzoyl]-4-piperidyl)-3,4- dihydro-2(1H)-quinolinone:
      reported vasopressin V1 receptor antagonist) were less potent antagonists of
      vasopressin-induced contractions (pA2: 7.31 and 5.6, respectively). The
      antagonist potency order (SR 49059 > OPC-31260 > OPC-21268) corresponds to the
      reported affinity order for the human cloned vasopressin V1 receptor. Therefore,
      the vasopressin V1 receptor antagonist SR 49059, but not OPC-21268, appears to be
      an appropriate tool to investigate further the role of vasopressin in
      pathological processes involving coronary vasoconstriction in humans.

PMID- 8566140
TI  - NG-nitro-L-arginine methyl ester protects against lipid peroxidation in the
      gerbil following cerebral ischaemia.
AB  - The aim of this study was to assess the role of nitric oxide (NO) in lipid
      peroxidation following 5 min of bilateral carotid occlusion in the Mongolian
      gerbil. The study consisted of 4 experimental groups (n = 10). Animals were
      either sham operated, subjected to bilateral carotid occlusion or administered
      the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg
      i.p.) 30 min, 6, 24 and 48 h following sham operation or 5 min bilateral carotid
      occlusion. Animals were killed 96 h post surgery and changes in the
      concentrations of malonaldehyde and 4 hydroxyalkenals (the main decomposition
      products of peroxides derived from polyunsaturated fatty acids and related
      esters) were measured in the hippocampus and cortex using the LPO-586
      colorimetric method. The results showed a significant increase in the
      concentrations of both decomposition products following 5 min of bilateral
      carotid occlusion. L-NAME administered to sham operated controls had no effect,
      but in those animals subjected to 5 min of bilateral carotid occlusion L-NAME
      significantly decreased the levels of both decomposition products. These results
      suggest that inhibition of NO synthase activity decreases lipid peroxidation in
      the gerbil model of cerebral ischaemia.

PMID- 8566141
TI  - Amantadine induces c-fos in rat striatum: reversal with dopamine D1 and NMDA
      receptor antagonists.
AB  - Amantadine (1-aminoadamantane) induced Fos expression in the central, dorsal
      medial and ventral-medial part of the striatum. The distribution pattern of Fos
      induced by amantadine was more similar to those seen with dopaminomimetics than
      with N-methyl-D-aspartate (NMDA) receptor antagonists. Pretreatment with the
      dopamine D1 receptor antagonist, SCH23390, and the NMDA receptor antagonist, MK
      801, blocked amantadine induction of Fos in the striatum. However, amantadine
      induction of Fos in the striatum was unaffected by the dopamine D2 receptor
      antagonist, sulpiride. These results suggest that amantadine induction of Fos in
      the rat striatum is related to dopamine D1 and NMDA receptors.

PMID- 8566142
TI  - Endothelin-3 can both facilitate and inhibit transmitter release in the guinea
      pig vas deferens.
AB  - Endothelin-3 (10 nM) produced a significant facilitation of the release of ATP
      from the in vitro guinea-pig vas deferens. This effect was converted to an
      inhibition of release by pretreatment with BQ-123, cyclo-(D-Trp,D-Asp,L-Pro,D
      Val,L-Leu), an endothelin ETA receptor antagonist. Desensitization of endothelin
      ETB receptors by sarafotoxin S6c antagonized, but did not reverse, the
      facilitatory effect of endothelin-3. The release of noradrenaline was not
      facilitated by endothelin-3; however, following pretreatment with BQ-123 the
      release of noradrenaline was reduced by the peptide. These results indicate that
      there may be both facilitatory and inhibitory prejunctional endothelin receptors
      and further suggest that the release of the sympathetic nerve cotransmitters ATP
      and noradrenaline may be differentially modulated.

PMID- 8566143
TI  - Antagonism of beta-adrenergic stimulation of L-type Ca2+ current by endothelin in
      guinea-pig atrial cells.
AB  - Experiments carried out with isolated guinea pig atrial cells, using the patch
      clamp technique, demonstrated that endothelin-1 reversed the increase in L-type
      Ca2+ current (ICaL) induced by isoprenaline. Similar effects of endothelin-1 were
      observed when ICaL was previously increased by forskolin or 8-bromo-cAMP. These
      results suggested that the endothelin antagonism of beta-adrenergic stimulation
      of ICaL was exerted independently of the cAMP-dependent phosphorylation pathway.

PMID- 8566144
TI  - Diadenosine-hexaphosphate is an inhibitory ligand of myocardial ATP-sensitive K+
      channels.
AB  - P1P6-di(adenosine-5')hexaphosphate (Ap6A) has been recently demonstrated in
      mammalian cells, yet its function remains unknown. Using single-channel current
      recordings, we studied the effect of Ap6A on guinea-pig cardiac ATP-sensitive K+
      (K(ATP) channels. When applied to the intracellular side of excised membrane
      patches, Ap6A produced a concentration-dependent inhibition (half-maximal
      inhibitory concentration: 14 microM; Hill coefficient: 1.1) of K(ATP) channel
      activity. We conclude that Ap6A is a potent inhibitory ligand of K(ATP) channels.

PMID- 8566145
TI  - Lidocaine action and conformational changes in cytoskeletal protein network in
      human red blood cells.
AB  - The mechanism of action of lidocaine, which is commonly used clinically as a
      local anesthetic, was studied in human red blood cells. The influx of
      [14C]lidocaine through the cell membrane induced reversible transformation of
      human red blood cells from discocytes to stomatocytes. This change in shape
      depended on the lidocaine concentration and required both ATP and carbonic
      anhydrase. The lidocaine-induced shape change occurred as a result of spectrin
      aggregation, which altered the intracellular environment of the human red blood
      cells, mediated by carbonic anhydrase and activation of vacuolar type H(+)-ATPase
      (V-ATPase). Lidocaine controlled the influx of 22Na into the human red blood
      cells in a concentration-dependent manner. When incubated in media containing 6
      chloro-9-[(4-diethylamino)-1-methyl-butyl]amino-2-methoxyacridine (mepacrine), an
      inhibitor of Na+ channels, human red blood cells changed shape from discocytes to
      stomatocytes and the intracellular pH decreased. This phenomenon was very similar
      to the shape change induced by lidocaine. These results suggest that the mode of
      action of lidocaine is related to a conformational change in the cytoskeletal
      protein network.

PMID- 8566146
TI  - Attenuation of morphine tolerance and dependence with the highly selective delta
      opioid receptor antagonist TIPP[psi].
AB  - We examined the effects of i.c.v. treatment with naltrindole, and the two highly
      selective peptide delta-opioid receptor antagonists H-Tyr-Tic-Phe-Phe-OH (TIPP)
      and H-Tyr-Tic psi [CH2-NH]-Phe-Phe- OH (TIPP[psi]), on the development of
      morphine tolerance and dependence. Each treatment significantly decreased
      naloxone-precipitated withdrawal, with TIPP[psi] reducing the most symptoms.
      TIPP[psi], but neither naltrindole nor TIPP, attenuated the development of
      analgesic tolerance in the tail-flick test. These results suggest that delta
      opioid receptors are critically involved in the development of morphine tolerance
      and dependence.

PMID- 8566147
TI  - Distinct receptors mediate gastrin-releasing peptide and neuromedin beta-induced
      delay of gastric of liquids in rats.
AB  - The present study was carried out to define which bombesin receptors are involved
      in the delay of gastric emptying induced by bombesin-like peptides. Adult male
      rats were fitted with gastric and jugular vein cannulas. Gastric emptying was
      determined 5 min after a 3-ml intragastric load of 0.9 M NaCl using phenol red as
      a marker. Mammalian bombesin-like peptides gastrin-releasing peptide-10 and
      neuromedin B both induced a delay of gastric emptying. When [Phe6]bombesin-(6-13)
      methyl ester, a selective antagonist of the gastrin-releasing peptide-preferring
      subtype of bombesin receptors, was injected 5 min before the agonists, the effect
      of gastrin-releasing peptide-10 was competitively inhibited, whereas that of
      neuromedin B remained unaffected. Our results indicate that gastrin-releasing
      peptide-10 and neuromedin B delay gastric emptying by acting on distinct
      receptors in rats, in vivo.

PMID- 8566148
TI  - Inotropic action of sigma receptor ligands in isolated cardiac myocytes from
      adult rats.
AB  - High affinity binding sites for sigma receptor ligands were found in membranes of
      cardiac myocytes from adult rats. The sigma receptor ligand (+)-3-hydroxyphenyl-N
      (1-propyl)piperidine ((+)-3-PPP) binds with a Kd of 17.9 +/- 4.0 nM and a Bmax of
      275 +/- 32.1 fmol/mg protein. Competition experiments of (+)-pentazocine with
      [3H]1,3-di-O-tolylguanidine ([3H]DTG) binding yielded a Ki of 6.1 +/- 1.3 nM. The
      majority of the sites (> 80%) were of the sigma 1 subtype. Exposure of isolated
      cardiomyocytes from adult rats to (+)-3-PPP (10 nM-1.0 microM) caused a marked
      concentration-dependent increase in the amplitude of systolic cell contraction,
      reaching 149% of control level, with an apparent ED50 value of 4.5 nM. The
      increase in the contraction amplitude was markedly inhibited by pretreatment with
      verapamil or thapsigargin. An increase in the amplitude of [Ca2+]i transients,
      similar to that in the amplitude of cell contraction, was observed in indo-1
      loaded cardiomyocytes exposed to 0.1 microM (+)-3-PPP. Exposure to 10 nM of
      haloperidol or (+)-pentazocine induced an increase in the amplitude of
      contraction, reaching 188% and 138% (respectively) of control level. A lower
      concentration of haloperidol or (+)-pentazocine (1 nM) did not induce an increase
      in the contraction amplitude but rather reduced the amplitude to 70-80% of
      control.

PMID- 8566149
TI  - G 619, a dual thromboxane synthase inhibitor and thromboxane A2 receptor
      antagonist, inhibits tumor necrosis factor-alpha biosynthesis.
AB  - G 619 is 3-carbamyl-(3'-picolyl)-4-methoxy-1-benzamide. The compound is
      structurally related to picotamide, a previously reported dual thromboxane
      synthase inhibitor/thromboxane A2 receptor antagonist, which displays inhibitory
      activity on tumor necrosis factor-alpha. The aim of the present work was to study
      the effect of G 619 on tumor necrosis factor-alpha synthesis both in vivo and in
      vitro. Salmonella enteritidis lipopolysaccharide was used to induce tumor
      necrosis factor-alpha production. Septic shock was produced in male rats by a
      single intravenous (i.v.) injection of 20 mg/kg (LD90) of Salmonella enteritidis
      lipopolysaccharide. Rats were pretreated with G 619 (50 mg/kg, i.v.) or vehicle
      (1 ml/kg, i.v.) 1 h before endotoxin challenge. Salmonella enteritidis
      lipopolysaccharide administration dramatically reduced survival rate (0%, 72 h
      after endotoxin administration), reduced mean arterial blood pressure, increased
      plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha and enhanced
      serum levels of tumor necrosis factor. Furthermore, endotoxic shock produced
      characteristic gastric damage, consisting of haemorrhagic infiltrates.
      Pretreatment with G 619 in vivo significantly protected against Salmonella
      enteritidis lipopolysaccharide-induced lethality (80% survival rate and 60%
      survival rate 24 h and 72 h after Salmonella enteritidis lipopolysaccharide
      injection, respectively), reduced hypotension, decreased plasma thromboxane B2
      and serum tumor necrosis factor-alpha levels and enhanced blood levels of 6-keto
      prostaglandin F1 alpha. In rat peritoneal macrophages, G 619 in vitro (25, 50 and
      100 microM) significantly blunted (P < 0.001) Salmonella enteritidis
      lipopolysaccharide-stimulated production of tumor necrosis factor-alpha, whereas
      it increased 6-keto-prostaglandin F1 alpha and cyclic AMP levels. The present
      data indicate that G 619 may be useful during disease states characterized by
      elevated tumor necrosis factor-alpha levels.

PMID- 8566150
TI  - Role of dopamine D1 and D2 receptors in the nucleus accumbens in jaw movements of
      rats: a critical role of the shell.
AB  - Given the differences in the dopamine neurotransmission between the shell and the
      core of the nucleus accumbens, as well as the differential involvement of these
      two domains in oral behaviour of rats, it was decided to determine whether or not
      dopamine D1 and/or dopamine D2 receptors differentially direct oral behaviour in
      these two domains in rats. Intra-accumbens injections of the dopamine D1 receptor
      agonist (+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-
      benzazepine (SKF 82958: 5 micrograms/0.2 microliters), the dopamine D2 receptor
      agonist quinpirole (10 micrograms/0.2 microliters) and their combination were
      used to assess the role of these accumbens domains in jaw movements of rats. The
      present study shows that the combined administration of SKF 82958 and quinpirole
      into the shell, but not the core, of the nucleus accumbens produced a highly
      significant increase in jaw movements, when doses which per se were nearly
      ineffective, were injected. This effect was fully inhibited by prior
      administration of either the dopamine D1 receptor antagonist R-(+)-7-chloro-8
      hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390: 0.5
      microgram/0.2 micrograms) or the dopamine D2 receptor antagonist (-)-sulpiride
      (25 ng/0.5 microliter) into the same region. It is concluded that dopamine D1 and
      D2 receptors in the shell, but not the core, of the nucleus accumbens are
      involved in jaw movements of the rat, providing the first piece of evidence that
      dopamine D1 and D2 receptors in the shell of the nucleus accumbens mediate a
      particular behaviour.

PMID- 8566151
TI  - Systemic and splanchnic oxygen supply-demand relationship with fenoldopam,
      dopamine and noradrenaline in sheep.
AB  - The effects of intravenous administration of fenoldopam (0.3-10 micrograms.kg
      1.min-1), dopamine (1-10 micrograms.kg-1.min-1) and noradrenaline (0.1-1
      micrograms.kg-1.min-1) on systemic and splanchnic haemodynamics and oxygen supply
      demand relationship were studied in 12 chronically instrumented, sedated sheep.
      Fenoldopam produced dose-dependent peripheral and splanchnic vasodilatation
      without change in arterial blood pressure. The coeliac trunk and portal vein
      blood flows were particularly sensitive to fenoldopam, whereas dopamine
      vasodilated these vascular beds only at high doses. Renal blood flow was not
      influenced by dopamine or fenoldopam, but decreased by noradrenaline. Fenoldopam
      maintained systemic oxygen extraction constant by increasing both oxygen supply
      and demand, while noradrenaline and dopamine increased oxygen supply more than
      demand, thus decreasing oxygen extraction. Both dopamine and fenoldopam increased
      oxygen delivery to the splanchnic organs while noradrenaline reduced it.
      Splanchnic oxygen consumption decreased with noradrenaline and increased with
      dopamine, resulting in a conserved oxygen extraction with both drugs, whereas
      oxygen consumption remained constant at all doses of fenoldopam infusion (i.e.
      dose-dependent decreased oxygen extraction). Both noradrenaline and fenoldopam,
      but not dopamine, were accompanied by increased portal lactataemia. We conclude
      that in sheep fenoldopam is a potent and selective splanchnic vasodilator but
      without vasodilatator effect on the renal circulation. The portal lactataemia
      associated with a decreased splanchnic oxygen extraction may present a
      significant limitation for some clinical applications of this drug.

PMID- 8566152
TI  - Striatal NMDA receptor subtypes: the pharmacology of N-methyl-D-aspartate-evoked
      dopamine, gamma-aminobutyric acid, acetylcholine and spermidine release.
AB  - We have examined the inhibitory potencies of MK 801, memantine, dextromethorphan,
      Mg2+ and of strychnine-insensitive glycine site antagonists on the N-methyl-D
      aspartate (NMDA)-evoked (300 microM) release of [14C]acetylcholine and
      [3H]spermidine or [14C] gamma-aminobutyric acid [14C]GABA and [3H]dopamine from
      rat striatal slices. MK 801, dextromethorphan and all glycine antagonists
      examined (7-chlorokynurenate, L-689,560 ((+/-)-trans-2-carboxy-5,7
      dichlorotetrahydroquinoline-4-phenylure a), 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX), 6,7-dichloroquinoxaline-2,3-dione (DNQX), and (+)-HA966 ((3-amino-1
      hydroxypyrrolidin-2-one) more potently inhibited NMDA-evoked dopamine and GABA
      release than acetylcholine and spermidine release by a factor of 3-21. MgCl2,
      which does not inhibit NMDA-evoked spermidine release, and memantine which only
      weakly antagonised NMDA-evoked spermidine release, inhibited NMDA-evoked
      dopamine, acetylcholine and GABA release with similar potencies. No
      pharmacological differences were observed between NMDA-evoked dopamine and GABA
      release. These findings extend those suggesting that NMDA-evoked acetylcholine
      and spermidine release are mediated by different NMDA receptor subtypes in the
      striatum and suggest a third native subtype with a distinct pharmacology that
      regulates striatal dopamine and GABA release.

PMID- 8566153
TI  - Effects of semotiadil, a novel Ca2+ channel antagonist, on the electrical
      activity of Langendorff-perfused guinea pig hearts in comparison with diltiazem,
      amlodipine and nifedipine.
AB  - Semotiadil, a new Ca2+ antagonist with a high vasoselectivity, in high
      concentrations depresses AV nodal conduction in a frequency-dependent manner. The
      aim of the present study was to investigate the effects of semotiadil on intact
      cardiac conduction and the pacemaker system in comparison with diltiazem,
      amlodipine and nifedipine. The effects were studied in isolated guinea pig hearts
      perfused by the method of Langendorff. Both semotiadil and diltiazem decreased
      markedly the sinus rate in a concentration-dependent manner whereas this was not
      the case in the presence of amlodipine and nifedipine. Semotiadil (10 microM)
      markedly prolonged sinus node recovery time and in the presence of diltiazem (10
      microM) in 5 out of 7 experiments an intermittent sinus node arrest occurred.
      Atrioventricular conduction and the effective refractory period of the AV node
      were most affected by diltiazem and semotiadil. The Ca2+ channel blocking
      compound semotiadil showed the most pronounced rate-dependent effects on the AV
      node. In the presence of diltiazem the QT interval became even shorter than in
      untreated hearts. In contrast, semotiadil did not act on the QT interval. In
      conclusion, as semotiadil exerts a clear rate-dependent effect on AV nodal
      conduction with a long time constant, it mimics the electrophysiological behavior
      of a substance of the verapamil type.

PMID- 8566154
TI  - Weak tolerance to the antinociceptive effect induced by the association of a
      peptidase inhibitor and a CCKB receptor antagonist.
AB  - We have recently shown that CCKB receptor antagonists such as PD-134,308, 4-([2
      [[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[tricyclo[3.3.1.1]dec - 2
      yloxy)carbonyl]amino]propyl]amino]-1-phenylethyl]amino)-4-oxo[R- (R*,R*)]
      butanoate-N-methyl-D-glucamine, are able to strongly potentiate antinociception
      induced by endogenous enkephalins, protected from degrading enzymes by the mixed
      inhibitor RB 101, N-[(R,S)-2-benzyl-3[(S)-(2-amino-4- methylthio)butyldithio]-1
      oxopropyl)-L-phenylalanine benzyl ester, at both spinal and supraspinal levels.
      In this study, the duration of this facilitatory response and the possible
      development of tolerance to this synergistic effect were investigated in the rat
      tail-flick test after acute and chronic treatment with PD-134,308 and RB 101. PD
      134,308 facilitated and prolonged the antinociceptive responses induced by RB 101
      (20 mg/kg, i.v.). The duration of the effect induced by PD-134,308 was also
      investigated by injecting this compound at different times before RB 101
      administration. In the case of the tail-flick test, the improvement of RB 101
      antinociceptive response was still significant 6 h after PD-134,308 (3 mg/kg,
      i.p.), whereas in the hot-plate test, this enhancement was only effective for 3 h
      after CCKB receptor antagonist administration. In the case of a repeated
      administration of RB 101, the potentiation induced by PD-134,308 on the
      antinociceptive effect produced by the first injection of RB 101 (20 mg/kg,
      i.v.), was found almost identical after a second administration of RB 101
      performed 190 min later. Chronic administration of RB 101 (20 mg/kg, i.v.) plus
      PD-134,308 (3 mg/kg, i.p.) administered for 5 days both once or twice per day,
      did not induce the development of tolerance to antinociception at the peak effect
      time. However, a decrease in the duration of the antinociceptive response was
      observed. These results indicate that the potent and long-lasting antinociceptive
      response induced by the coadministration of the peptidase inhibitor and the CCKB
      receptor antagonist could have interesting perspectives in the clinical treatment
      of pain.

PMID- 8566155
TI  - Dexamethasone and methylprednisolone affect rat peritoneal phagocyte
      chemiluminescence after administration in vivo.
AB  - Production of reactive oxygen compounds by peritoneal monocytes/macrophages was
      studied in rats exposed to dexamethasone or methylprednisolone in the drinking
      water. Luminol-amplified chemiluminescence was measured in preparations of
      peritoneal leukocytes activated ex vivo by serum opsonized zymosan, N-formyl-L
      methionyl-L-leucyl-L-phenylalanine (fMLP) or phorbol 12-myristate 13-acetate
      (PMA). After dexamethasone administration for 1 day (approximately 0.13 mg/kg per
      24 h) a significant reduction in chemiluminescence was found in cells stimulated
      with serum opsonized zymosan, while responses to fMLP and PMA stimulation were
      significantly reduced after 2 days. The maximal inhibition obtained after 5-8
      days of dexamethasone administration (plasma levels < 5 nM) was 92.0 +/- 1.2%,
      87.6 +/- 0.2% and 84.5 +/- 3.1% in cells stimulated with serum opsonized zymosan,
      fMLP and PMA, respectively. Administration of dexamethasone or methylprednisolone
      for 48 h gave a dose-dependent reduction of chemiluminescence. ED50 values of
      dexamethasone were estimated at 0.06-0.15 mg/kg for the different stimulators
      (plasma concentrations 5-10 nM). Estimated ED50 values for methylprednisolone
      were 35-36 mg/kg. Since the percentage of mononuclear phagocytes in the
      peritoneal cell population did not change significantly with dose or time of
      dexamethasone exposure, this study indicates that glucocorticoids have a
      depressive effect on the monocyte/macrophage 'respiratory burst' in vivo. The
      results are consistent with the hypothesis that these effects are mediated by
      glucocorticoid receptors. Although the pathway activated by serum opsonized
      zymosan was more rapidly inhibited than the fMLP- and PMA-activated pathways, the
      responses induced by the different stimulators were similarly affected,
      suggesting a modulation of common components in the activation pathways, possibly
      protein kinase C or the NADPH-oxidase complex, after administration of low
      pharmacological doses of glucocorticoids in vivo.

PMID- 8566156
TI  - Inhibition of catecholamine synthesis by proadrenomedullin N-terminal 20 peptide
      in cultured bovine adrenal medullary cells.
AB  - In cultured bovine adrenal medullary cells, proadrenomedullin N-terminal 20
      peptide (PAMP), at concentrations > or = 3 microM, inhibited carbachol-induced
      [14C]catecholamine synthesis from [14C]tyrosine. Carbachol-induced activation of
      tyrosine hydroxylase was also attenuated by PAMP. These results suggest that PAMP
      is a novel endogenous peptide that regulates catecholamine synthesis via the
      suppression of its rate-limiting enzyme in adrenal medullary cells.

PMID- 8566157
TI  - Effect of vinconate on the extracellular levels of dopamine and its metabolites
      in the rat striatum: microdialysis studies.
AB  - The effects of (+/-)-methyl-3-ethyl-2,3,3 alpha, 4-tetrahydro-1H- indolo[3,2,1
      de][1,5]naphthyridine-6-carboxylate hydrochloride (vinconate), an
      indolonaphthyridine derivative, on the extracellular levels of dopamine and its
      metabolites in the rat striatum were examined using brain microdialysis. Single
      administration of vinconate (10, 100 mg/kg i.p.) increased the extracellular
      level of dopamine and its metabolites. This enhancing effect of vinconate was
      antagonized by scopolamine (10 microM), a muscarinic receptor antagonist, which
      was added to the perfusate from 30 min before vinconate treatment. These findings
      suggest that vinconate, even when systemically administered, enhances the
      endogenous release of dopamine in the striatum, probably via the stimulation of
      presynaptic muscarinic receptors.

PMID- 8566158
TI  - Expression of endogenous muscarinic acetylcholine receptors in Chinese hamster
      ovary cells.
AB  - Chinese hamster ovary (CHO) cells are commonly used for expression of the genes
      of cloned neurotransmitter receptors to study their pharmacology and coupling to
      signal transduction pathways. It is usually assumed that host cells do not
      endogenously express the specific receptor under consideration. We demonstrate in
      this report that CHO cells contain endogenous functional muscarinic acetylcholine
      receptors which, in some circumstances, might complicate interpretation of data
      related to the properties of exogenously expressed receptors.

PMID- 8566159
TI  - Mystixin-7 and mystixin-11 increase cytosolic free Ca2+ and inositol
      trisphosphates in human A-431 cells.
AB  - Mystixin-7 and mystixin-11, small peptides structurally related to corticotropin
      releasing factor (CRF), have been shown to attenuate vascular leakage in injured
      skin. The goal of this study was to characterize changes in cytosolic Ca2+
      concentration ([Ca2+]i) in human epidermoid A-431 cells treated with these two
      peptides and to investigate the mechanisms by which these changes occurred. The
      resting [Ca2+]i in A-431 cells at 37 degrees C was 76 +/- 2 nM (n = 373). When
      cells were treated with either peptide, [Ca2+]i increased immediately. The
      increase depended on the peptide concentration, with a median effective
      concentration of 299 +/- 9 pM for mystixin-7 and 2.23 +/- 0.04 pM for mystixin
      11. The increases also depended on extracellular Ca2+ and were blocked by Cd2+,
      Co2+, verapamil, and nifedipine. alpha-Helical CRF-(9-41), a synthetic CRF
      receptor antagonist, and pertussis toxin also blocked the increase in [Ca2+]i
      induced by the two peptides. Taken together, these results suggest that mystixin
      7 and mystixin-11 interact with CRF receptors to activate pertussis-sensitive G
      proteins coupled to L-type Ca2+ channels that allow an uptake of extracellular
      Ca2+. Because U-73122, an inhibitor of 1,4,5-inositol trisphosphate production,
      partially inhibited the increase in [Ca2+]i, we measured inositol trisphosphates
      in cells stimulated by the two peptides. Both increased inositol trisphosphate
      levels within 1 min. The increase was inhibited by the removal of extracellular
      Ca2+ or treatment with U-73122. The results suggest that the Ca2+ influx
      stimulated by mystixin-7 and mystixin-11 induces an increase in inositol
      trisphosphates, resulting in a mobilization of Ca2+ from 1,4,5-inositol
      trisphosphate-sensitive Ca2+ pools.

PMID- 8566160
TI  - Role of opioid peptides in the regulation of DNA synthesis in immature rat
      uterus.
AB  - The effects of a single dose of naloxone and of [D-Met2,Pro5]enkephalinamide on
      the DNA synthesis in the uterus of 7, 14 and 21-day-old rat were studied. After
      [D-Met2,Pro5]enkephalinamide treatment, an age-dependent decrease in in vitro
      [3H]thymidine incorporation into DNA was observed in all studied age groups. In
      the 21-day-old age group a reduced rate of DNA synthesis was detected for 12 h
      after [D-Met2,Pro5]enkephalinamide treatment followed by the return to control
      values at 24 h. The rate of inhibition was more marked in the younger age groups.
      The effect was also more pronounced in younger animals. Specific [3H]naloxone
      binding was detected both in membrane and nuclear fractions of uterine
      homogenates. While no age-related changes in binding affinities were found, the
      number of binding sites varied characteristically during development. Our data
      suggest the novel involvement of opioid peptides and their receptors in the
      regulation of uterine development.

PMID- 8566161
TI  - Potentiation of glucocorticoid-mediated gene expression by the novel benzoquinone
      derivative (2E)-3-[5-(2,3-dimethoxy-o-methyl-1, 4-benzoquinoyl)]-2-nonyl-2
      propenoic acid (E3330).
AB  - We examined the effects of the novel benzoquinone derivative (2E)-3-[5-(2,3
      dimethoxy-o-methyl-1,4-benzoquinoyl)]-2-nonyl -2-propenoic acid, E3330, on the
      functional activity of the glucocorticoid receptors. For that purpose we used a
      cloned CHOpMTGR cells, in which human glucocorticoid receptor cDNA was stably
      transfected and glucocorticoid receptor was expressed at high levels. After
      treatment of CHOpMTGR cells with E3330, neither the ligand binding activity nor
      immunoreactivity of the glucocorticoid receptor was affected. Moreover, E3330 did
      not affect the sequence-specific DNA binding activity of partially-purified
      glucocorticoid receptor in vitro. However, a glucocorticoid-inducible promoter
      was activated by E3330 in a dose-dependent fashion in the presence of the
      synthetic ligand dexamethasone. Interestingly, E3330 increased nuclear
      translocation of the glucocorticoid receptor in a ligand-independent fashion,
      indicating that E3330, through facilitation of the translocation of the
      glucocorticoid receptor, augments glucocorticoid-mediated gene transcription.

PMID- 8566163
TI  - Functional domains of the C-terminus of the rat angiotensin AT1A receptor.
AB  - Previous work has shown that truncating the carboxyl terminus (C-terminus) of the
      rat angiotensin AT1A receptor to 309 amino acids abolished G-protein coupling and
      receptor internalization. This suggests that domains responsible for these
      functions lie beyond amino acid 309 of the C-terminus. The objective of this
      study was to determine the effect on angiotensin AT1A receptor function and
      regulation of deleting 41 amino acids from the C-terminus, which include the
      putative protein kinase C phosphorylation sites. Using site directed mutagenesis,
      the codon for Tyr319 was converted to a stop codon and the resulting truncated
      receptor permanently expressed in cultured human kidney cells. The properties of
      the truncated receptor were compared to those of the full length receptor.
      Expression of the truncated receptor was confirmed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis analysis of photolabelled membrane
      preparations. Angiotensin II activation of both full length and truncated
      receptors resulted in mobilization of inositol phosphates. However, whereas this
      was associated with rapid internalization of the full length receptor, the
      truncated receptor failed to internalize. Furthermore, pretreatment of cells with
      phorbol 12-myristate 13-acetate, a direct activator of protein kinase C, markedly
      attenuated the full length, but no the truncated receptor's ability to mobilise
      inositol phosphates. Thus, we conclude that the domain between amino acids 309 &
      318 is important for G-protein coupling; that amino acids beyond 318 regulate
      internalization and one or more of the putative protein kinase C phosphorylation
      sites, present in the C-terminus of the angiotensin At1A receptor, actively
      regulate the receptor.

PMID- 8566162
TI  - Properties of TAN-67, a nonpeptidic delta-opioid receptor agonist, at cloned
      human delta- and mu-opioid receptors.
AB  - 2-methyl-4a alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha-octahydro
      quinolino[2,3,30g]isoquinoline (TAN-67) is a nonpeptidic delta-opioid receptor
      agonist. This report describes its receptor binding affinity and agonist potency
      at human and mouse delta and mu-opioid receptors. The binding affinities of TAN
      67 and the cyclic enkephalin analog, (D-Pen2, 4'-Cl-Phe4, D-Pen5]enkephalin (pCl
      DPDPE) were measured by radioligand binding inhibition studies at mouse and human
      variants of the delta and mu-opioid receptor using [3H]Naltrindole and [3H]D-Phe
      Cys-Tyr-D-Trp-Orn-Thr -Pen-Thr-NH2, respectively. TAN-67 showed high binding
      affinity (Ki = 0.647 nM) at the human delta-opioid receptor and high delta-opioid
      receptor binding selectivity ( > 1000-fold) relative to the human mu-opioid
      receptor. TAN-67 also showed high potency (EC50 = 1.72 nM) for the inhibition of
      forskolin-stimulated cAMP accumulation at human delta-opioid receptors expressed
      by intact Chinese hamster ovary cells but low potency (EC50 = 1520 nM) at human
      mu-opioid receptors expressed by intact B82 mouse fibroblast cells. The results
      show that TAN-67 has similar binding affinities, selectivity and potencies as pCl
      DPDPE at human delta and mu-opioid receptors. These results combined with the
      nonpeptidic structure of TAN-67 suggest that this compound has therapeutic
      potential as a delta-opioid receptor agonist.

PMID- 8566164
TI  - Effects of AMPA receptor modulators on the production of arachidonic acid from
      striatal neurons.
AB  - The abilities of different compounds acting at alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA) receptors to modulate the overflow of [3H]arachidonic
      acid from rat striatal neurons were examined. The combination of AMPA (0.1 mM)
      and carbachol (1mM) stimulated [3H]arachidonic acid production, this effect could
      be dose-dependently enhanced by the newly discovered allosteric modulator of AMPA
      receptors: cyclothiazide. Competitive (6-cyano-7-nitroquinoxaline-2,3-dione
      [CNQX] and 6-(1-imidazolyl)-7-nitroquinazoline-2,3-dione [YM 900]) and non
      competitive antagonists, like 1-(amino)-phenyl)-4-methyl -7,8-methylenedioxy-5H
      2,3-benzodiazepine (GYKI 52466), antagonized the responses induced by either AMPA
      + carbachol or AMPA + carbachol + cyclothiazide. In order to appreciate the
      respective part of AMPA-versus kainate-preferring receptors experiments were
      performed with kainic acid (0.1 mM) and the more specific kainate agonist domoic
      acid (0.1 mM). Kainic acid behaves like AMPA, but the response induced by the
      combination domoic acid + carbachol could not be potentiated by cyclothiazide. On
      the contrary, concanavalin A potentiated the responses evoked by kainic acid or
      domoic acid (in combination with carbachol) but did not enhance the AMPA-evoked
      response. It could be concluded that both AMPA- and kainate-preferring receptors
      are present in cultured rat striatal neurons and that these two types of
      receptors were involved together with muscarinic receptors in the overflow of
      [3H]arachidonic acid.

PMID- 8566166
TI  - Bradykinin receptors in signal transduction pathways in peritoneal guinea pigs
      macrophages.
AB  - The presence of a bradykinin receptor on guinea pig peritoneal macrophages was
      evidenced by binding studies and by the effect of bradykinin on activation of the
      phospholipase C and the increase in intracellular calcium concentration
      ([Ca2+]i). Binding studies demonstrated a specific, saturable binding for
      [3H]bradykinin inhibited by the bradykinin B2 (HOe 140) but not bradykinin B1
      (des-Arg9[Leu8]bradykinin) receptor antagonist. Scatchard analysis revealed a
      single class B2 bradykinin binding site with a binding affinity (kd) of 0.8 nM
      and a receptor concentration (Bmax) of 35 fmol/5 x 10(6) cells, representing
      approximately 4000 bradykinin receptors per cells. Kinetic studies confirmed the
      presence of this single binding site by the determination of similar binding
      affinity. Activation of peritoneal macrophages by bradykinin resulted in a time-
      and dose-dependent release of inositol phosphates determined by anion exchange
      chromatography and intracellular calcium analyzed using fura-2/AM. The increase
      in [Ca2+]i induced by bradykinin was blocked by the specific bradykinin B2
      receptor antagonist HOE 140 but not the bradykinin B1 receptor antagonist des
      Arg9[leu8]-BK. These studies provide novel information regarding the nature of
      kinin receptors on guinea pig peritoneal macrophages and their signal
      transduction pathways.

PMID- 8566165
TI  - Ca(2+)-activated outward-rectifier K+ channels and histamine release by rat
      gastric enterochromaffin-like cells.
AB  - Gastric enterochromaffin-like (ECL) cells were isolated from rat gastric fundic
      mucosa by Percoll density-gradient centrifugation and counter-flow elutriation.
      About 67% of cells in the purified cell suspension were ECL cells, which were
      reacted with anti-histidine decarboxylase antibody. A23187, a calcium ionophore,
      at 0.1-10 microM induced histamine release from ECL cell-rich suspension,
      indicating that the Ca2+ pathway is involved in the mechanism of histamine
      release from the ECL cells. A23187 at 5 microM significantly increased outward
      rectifier cationic current in 62% of cells in the ECL cell-rich factions. A23187
      sensitive cells showed acridine orange uptake. In single-channel recordings, a
      Ca(2+)-dependent outward-rectifier K+ channel of large conductance (146 +/- 22
      picosiemens) was found in the cell that showed acridine orange uptake. The
      channel opened in a voltage-dependent manner at 0.1 microM of intracellular free
      Ca2+ concentration. These results may suggest that opening of the Ca(2+)
      activated K+ channel is one of the steps involved in the mechanism of histamine
      release in ECL cells.

PMID- 8566167
TI  - The effect of hydrogen peroxide/L-histidine-induced DNA single- vs. double-strand
      breaks on poly(ADP-ribose)polymerase.
AB  - L-Histidine markedly increases the ability of hydrogen peroxide to induce DNA
      cleavage and this effect is associated with a 3-aminobenzamide-inhibitable
      decline in NAD+ levels, an event which very likely reflects an enhanced
      stimulation of the enzyme poly(ADP-ribose)polymerase. 3-Aminobenzamide slowed
      down the removal of alkaline elution-detected strand breaks induced by either
      H2O2 alone (producing only DNA single-strand breaks) or associated with L
      histidine (resulting in the formation of both single-strand breaks and DNA double
      strand breaks), and the extent of inhibition was similar under the two
      experimental conditions. 3-Aminobenzamide did not affect the rate of rejoining of
      DNA double-strand breaks generated by the cocktail H2O2/L-histidine. The above
      results suggest that these double-strand breaks have hardly any effect on the
      induction of poly(ADP-ribose)polymerase activity, a conclusion that is consistent
      with the observation that the activity of this enzyme appears to be basically
      identical under conditions that abolish the formation of DNA double-strand
      breaks, in the absence of measurable variations in the level of induction of DNA
      single-strand breaks (e.g. in the presence of an excess of L-glutamine, a
      competitive inhibitor of L-histidine uptake). Finally, 3-aminobenzamide did not
      affect the toxicity of the oxidant, both in the absence and presence of L
      histidine.

PMID- 8566168
TI  - Receptor-induced heterologous desensitization of receptor-regulated phospholipase
      C.
AB  - Activation of the P2Y purinoceptor on turkey erythrocytes results in a G11
      mediated activation of a phospholipase C-beta isoenzyme and hydrolysis of
      polyphosphoinositides. The role of the protein kinase C and Ca(2+)-mobilizing
      arms of the inositol lipid signalling cascade in P2Y purinoceptor-induced
      desensitization of phospholipase C has been examined using erythrocytes as a
      model system. Preincubation of intact erythrocytes with either P2Y purinoceptor
      agonist, ADP beta S, or the protein kinase C-activating phorbol ester, phorbol 12
      myristate, 13 acetate (PMA), resulted in a time of preincubation-dependent
      decrease in guanine nucleotide-, P2Y purinoceptor-, and beta-adrenoceptor
      stimulated phospholipase C activities in membranes isolated from these cells. The
      extent of heterologous desensitization induced by ADP beta S and PMA were
      additive suggesting that they did not share a common mechanism. A lack of
      involvement of activation of protein kinase C in P2Y purinoceptor-induced
      heterologous desensitization was further supported by the observation that
      although protein kinase C inhibitors or down-regulation of protein kinase C
      resulted in a loss of PMA-induced desensitization, neither treatment affected the
      extent of P2Y purinoceptor-induced desensitization. In addition, elevation of
      intracellular Ca2+ or prevention of its elevation did not induce heterologous
      desensitization and had no effect on the desensitization induced by ADP beta S.
      Thus, neither the protein kinase C nor Ca2+ mobilizing arms of the inositol lipid
      signalling pathway appear to be involved in P2Y purinoceptor promoted
      heterologous desensitization of phospholipase C. These results are consistent
      with the existence of a novel feedback pathway for agonist-induced heterologous
      desensitization of a second messenger generating enzyme. Preincubation of cells
      with ADP beta S or the beta-adrenoceptor agonist, isoproterenol, followed by
      rechallenge with each of the receptor agonists revealed that receptor-specific
      desensitization occurs in addition to heterologous desensitization. Thus,
      multiple mechanisms account for agonist-induced desensitization of the inositol
      lipid signalling system of turkey erythrocytes.

PMID- 8566169
TI  - Opiates inhibit ion conductances elicited by cell swelling and cAMP in cultured
      cells.
AB  - The effect of several opiate compounds on I- efflux was investigated in cultured
      cell lines. I- efflux was evoked by two distinct stimuli, namely cell swelling
      and elevation of cellular cAMP levels by prostaglandin E2. Cells expressing the
      multidrug resistance P-glycoprotein were found to have increased I- efflux in
      response to hypo-osmotic challenge. This increased I- efflux in P-glycoprotein
      containing cells was reduced to levels found in parental cells by the opiates
      morphine, pentazocine and naloxone. Addition of prostaglandin E2 to T84 cells
      resulted in elevated cellular cAMP levels and a significant I- efflux. This cAMP
      stimulated efflux was also inhibited by several opiates. None of the opiates was
      able to alter cAMP levels or protein kinase A mediated phosphorylation of
      immunoprecipitated cystic fibrosis transmembrane conductance regulator (CFTR) Cl-
      channel in T84 cells. The ability of opiates to alter ion conductances is
      discussed in relation to the anti-diarrheal effects of these compounds.

PMID- 8566170
TI  - Characterization of a binding site for angiotensin IV on bovine aortic
      endothelial cells.
AB  - We have characterized a specific binding site for angiotensin IV on bovine aortic
      endothelial cell membranes. Pseudo-equilibrium studies at 37 degrees C for 2 h
      have shown that this binding site recognizes angiotensin IV with a high affinity
      (Kd = 0.71; average of two experiments that yielded values of 0.71 and 0.72 nM).
      The binding site is saturable and relatively abundant with a maximal binding
      capacity of 0.59 pmol/mg protein (average of two experiments that yielded values
      of 0.39 and 0.78 pmol/mg of protein). Non-equilibrium kinetic analyses at 37
      degree C revealed a calculated Kd of 59 pM (average of two experiments that
      yielded values of 67 and 50 pM). The binding site displays a high affinity for
      angiotensin receptors AT1 or AT2. An analysis of specificity showed that the
      binding site displays a high affinity for angiotensin IV, low affinities for
      angiotensin II, [Sar1, Val5, Ala8]angiotensin II and does not recognize L-158,809
      (5,7-dimethyl-2-ethyl-3-[(2'-(1 H-tetrazole-5-yl)[1,1'-biphenyl]-4-yl)methyl]-3H
      imidazo[4, 5-beta]pyridine H2O) and PD 123319 (1-[4-dimethylamino)3
      methylphenyl]methyl-5-(diphenylacetyl) 4,5,6,7-tetrahydro-1 H-imidazo[4,5
      c]pyridine-6-carboxylic acid). A few unrelated hormones (bradykinin, [Arg8]
      vasopressin, endothelin-1, atrial natriuretic factor, isoproterenol and
      adrenocorticotropic hormone) were unable to inhibit any 125I-angiotensin IV
      binding. The affinities of different structural analogues of angiotensin IV
      revealed that the N-terminal position is critical for receptor recognition and
      the C-terminal proline is also important. GTP gamma S and polyvinyl sulfate did
      not affect the binding, suggesting that the receptor is not coupled to a G
      protein. The divalent cations Mg2+ and Ca2+ were shown to diminish the binding of
      125I-angiotensin IV. Cross-linking of 125I-angiotensin IV to bovine aortic
      endothelial cell membranes in the presence of disuccinimidyl suberate, followed
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed
      a major band of 186 +/- 12 kDa. The presence in high concentration of this
      angiotensin binding site on aortic endothelial cells suggest the existence of a
      novel mechanism involved in the control of vascular tone or vascular
      permeability.

PMID- 8566171
TI  - Mevalonate pathway and isoprenoids regulate human bronchial myocyte
      proliferation.
AB  - The role of mevalonate and geranylgeraniol in the control of cellular
      proliferation of cultured human bronchial myocytes was examined by investigating
      the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase, the rate-limiting enzyme in mevalonate synthesis. Simvastatin
      inhibited the rate of growth of human bronchial smooth muscle cells in a
      concentration-dependent manner, with an IC50 value of 0.97 +/- 0.1 microM.
      Mevalonate (100 microM), as well as geranylgeraniol (5 microM), at their highest
      non-toxic concentrations, restored cell proliferation to control levels.

PMID- 8566172
TI  - Effect of channel modulation and pH on IsK inhibition by the novel class III
      antiarrhythmic azimilide (NE-10064).
AB  - Inhibition of human IsK channels expressed in Xenopus oocytes by the novel class
      III antiarrhythmic azimilide was studied under distinct treatments known to
      increase IsK (hypotonic solution, A23187 and isoproterenol) Azimilide inhibited
      IsK under all conditions with similar potency. Reduction of ionic strength or pH
      changes from pH 6.5 to 8.5 did not alter IsK amplitude. However, inhibition of
      IsK by azimilide was decreased by reduced pH, but not by reduced ionic strength.
      Further, the apparent affinity of azimilide was increased more than tenfold by
      increasing pH from 6.5 to 8.5. The data suggest that the neutral form of
      azimilide, a weak base, inhibits IsK via a lipophilic protein-drug interaction.
      pH-dependence of azimilide may significantly alter its effects on IsK under
      distinct pathophysiological conditions (acidosis vs. alkalosis) and in distinct
      locations (heart vs. kidney).

PMID- 8566173
TI  - Mitogenic effect of serotonin in human small cell lung carcinoma cells via both 5
      HT1A and 5-HT1D receptors.
AB  - We have recently shown that the mitogenic effect of serotonin (5
      hydroxytryptamine, 5-HT) on human small lung carcinoma (SCLC) cells is at least
      partly due to stimulation of a 5-HT1D receptor type. We now report that the 5
      HT1A receptor agonist R(+)-8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT) is
      also capable of stimulating [3H]thymidine incorporation into SCLC GLC-8 cells,
      although with lower efficacy than 5-HT. The simultaneous administration of
      maximal doses of 8-OH-DPAT and the 5-HT1D receptor agonist sumatriptan reproduced
      the maximal [3H]thymidine incorporation observed with 5-HT alone. The 5-HT1A
      receptor antagonists spiperone and SDZ 216-525 completely abolished the effect of
      8-OH-DPAT (IC50 30 nM for both drugs) behaving as pure antagonists. Accordingly,
      the two drugs partially inhibited the mitogenic effect of 5-HT. These data
      indicate that the mitogenic effect of 5-HT in SCLC cells involves both 5-HT1A and
      5-HT1D receptor types.

PMID- 8566174
TI  - The inositol phosphate response to thrombin in rat right atria differs from the
      response to noradrenaline.
AB  - Addition of thrombin to isolated [3H]inositol-labelled rat right atria stimulated
      the release of 3H-labelled inositol phosphates. The thrombin response was smaller
      than the response to noradrenaline and generated a different spectrum of inositol
      phosphates. Unlike the inositol phosphate response to noradrenaline, the thrombin
      response was inhibited by pertussis toxin treatment and by the phospholipase C
      inhibitor U-73122 (1-(6-((17 beta-3- methoxyestra-1,3,5(10)-trien-17
      yl)amino)amino)hexyl)-1H- pyrrole-2, 5-dione). The data indicate that the
      thrombin stimulation involves different G-proteins and phospholipase C isoforms
      from those which couple alpha 1-adrenoceptors in the myocardium.

PMID- 8566175
TI  - Possible mechanism of oxygen radical production by human eosinophils mediated by
      K+ channel activation.
AB  - Quinidine hydrochloride, as potent K+ channel blocker, reduced luminol-dependent
      chemiluminescence products evoked by the addition of the calcium ionophore A23187
      to eosinophils from patients with hypereosinophilic syndrome (n = 3) in a
      concentration-dependent manner (10-5 mM quinidine). A23187 is known to cause
      increases in intracellular Ca2+ concentrations in eosinophils. Our results
      indicate that the production of reactive oxygen species by human eosinophils may
      be affected by Ca(+)-activated K+ channels.

PMID- 8566176
TI  - Deriving the therapeutic concentrations for clozapine and haloperidol: the
      apparent dissociation constant of a neuroleptic at the dopamine D2 or D4 receptor
      varies with the affinity of the competing radioligand.
AB  - The apparent dissociation constant, Ki, for a neuroleptic at the dopamine D2 or
      D4 receptor was consistently higher when competed against [3H]nemonapride than
      against [3H]spiperone which was in turn higher than that against [3H]raclopride.
      This finding obtained for all four types of dopamine receptors studied, including
      the native dopamine D2 receptor in the anterior pituitary tissue, the human
      D2long receptor, the human D2short receptor and the human D4.4 receptor. Some
      neuroleptics revealed a difference of over 10-fold between the Ki using
      [3H]nemonapride and the Ki using [3H]raclopride. The KD values of the three 3H
      ligands and the neuroleptic Ki values were lower when using a much lower
      concentration of tissue, indicating that depletion of ligand presumably accounted
      for the phenomenon. The Ki values of each neuroleptic were related to the the
      tissue/buffer partition coefficients of the three 3H-ligands. Extrapolating the
      neuroleptic Ki value down to a tissue/buffer partition coefficient of unity or
      zero led to a Ki value for competition versus a water-soluble ligand such as
      dopamine. Clozapine extrapolated to a Ki value of 1.3 nM. Direct measurement gave
      a Ki value of 1.6 nM for [3H]clozapine at the dopamine D4 receptor. When
      competing versus endogenous dopamine, this clozapine value of 1.6 nM would rise
      to 20 nM for the blockade of 75% of dopamine D4 receptors, matching the observed
      therapeutic concentration of 18 nM. These data also explain why clozapine
      occupies 48% of the D2 receptors in patients when measured with [11C]raclopride,
      but between 0% and 22% when measured with [18F]methylspiperone or
      [18F]fluoroethylspiperone.

PMID- 8566177
TI  - Thrombin triggers the de novo expression of an inducible NO synthase in porcine
      aortic valve endothelial cells.
AB  - The nitric oxide (NO) production by porcine aortic valve endothelial cells was
      estimated in cusps incubated at 37 degrees C by measuring their cyclic GMP
      content and the nitrite levels of the incubation medium. After a stabilization
      period, incubation for 5 min with acetylcholine, bradykinin, ADP and bovine
      thrombin resulted in a receptor-mediated increase in cyclic GMP which could be
      blocked by EGTA, N-omega-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl
      L-arginine (L-NMMA). Incubation with lipopolysaccharide (endotoxin) from E. coli
      O111:B4 or bovine for 5 h, dose-dependently increased nitrite production as well
      as cyclic GMP content. The elevated nitrite production was completely abolished
      in the presence of the protein synthesis inhibitor cycloheximide, was reduced by
      more than 50% by dexamethasone but was not affected by EGTA. L-NMMA dose
      dependently reduced the increased nitrite production and cyclic GMP content.
      These results suggest that besides the presence of a constitutive NO synthase in
      porcine aortic valve endothelial cells thrombin, like lipopolysaccharide,
      triggers the de novo expression of an inducible Ca(2+)-independent NO synthase.

PMID- 8566178
TI  - Anti-calmodulin potency of indol alkaloids in in vitro systems.
AB  - We have demonstrated that bis-indol Vinca alkaloids of anti-mitotic activities
      (vinblastine, vincristine, and navelbine) bind to calmodulin in a Ca(2+)
      dependent manner. We designed direct binding tests (fluorescence energy transfer
      and circular dichroism measurements) to quantify the interactions of bis-indol
      derivatives with calmodulin. The dissociation constants of calmodulin-navelbine
      and calmodulin-vinblastine complexes with 1:1 stoichiometry are 0.5 microM and 3
      microM, respectively. These values indicate that the binding affinities of these
      Vinca alkaloids to calmodulin and tubulin are comparable. Immunological, enzyme
      kinetic and fluorescence anisotropy measurements showed that bis-indol alkaloids
      inhibit the interactions of calmodulin with target proteins. The results of
      indirect enzyme-linked immunosorbent assay showed that bis-indol alkaloids
      effectively antagonize with anti-calmodulin antibody for calmodulin binding (IC50
      = 90 microM, 400 microM, and 430 microM for navelbine, vincristine and
      vinblastine, respectively). According to the fluorescence anisotropy and enzyme
      kinetic measurements, vinblastine, vincristine and vinblastine, similarly to
      trifluoperazine, the classic calmodulin antagonist, compete with target enzyme
      [phosphofructokinase (ATP: D-fructose 6-phosphate 1-phosphotransferase, EC
      2.7.1.11)] for an inhibitory effect either on immunocomplex formation or on
      calmodulin-enzyme interaction. Navelbine appeared in our tests as the most potent
      drug in inhibiting the association of calmodulin to target proteins in comparison
      to other bis-indol derivatives. Since navelbine and vinblastine possess identical
      vindoline moiety, although they differ in the catharantine part, the difference
      in anti-calmodulin potencies is suggested to reside predominantly on this portion
      of the molecules. These findings might establish the pharmacological importance
      of these activities in the specificity and toxicity of the drugs.

PMID- 8566179
TI  - Lipid A and the lipid A analogue anti-tumour compound ONO-4007 induce nitric
      oxide synthase in vitro and in vivo.
AB  - The ability of lipid A and the antitumour compound, ONO-4007 (sodium2-deoxy-2-[3S
      (9-phenylnonanoyloxy)tetradecanoyl] amino-3-O-(9phenylnonanoyl)-D-glucopyranose 4
      sulphate) to induce nitric oxide (NO) synthase was investigated in vitro and in
      vivo, in comparison to the effects of lipopolysaccharide and di- and
      monophosphoryl lipid A. In J744.2 macrophages, lipopolysaccharide, di-and
      monophosphoryl lipid A and ONO-4007 (10(-9) - 10(-5) g/ml) alone, or in
      combination with interferon-gamma, induced NO synthase (order of potency:
      lipopolysaccharide > diphosphoryl lipid A > monophosphoryl lipid A > ONO-4007).
      ONO-4007 increased the activity of the inducible NO synthase in the lung of
      anesthetised rats (20% of the increased caused by bacterial lipopolysaccharide).
      Thus, ONO-4007 is a weak inducer of the inducible isoform of NO synthase in vitro
      and in vivo. The finding that di- and monophosphoryl lipid A also induce NO
      synthase indicates that the lipid A moiety of lipopolysaccharide contributes to
      the induction of NO synthase by lipopolysaccharide. The induction of NO synthase
      by ONO-4007, resulting in the formation of cytotoxic NO may contribute to the
      antitumour activity of the compound.

PMID- 8566180
TI  - Involvement of cyclic AMP in the effects of phosphodiesterase IV inhibitors on
      arachidonate release from mononuclear cells.
AB  - The effects of selective phosphodiesterase inhibitors, cyclic AMP (cAMP)
      elevating agents and stable analogues of cyclic nucleotides, on the release of
      arachidonate induced by N-formyl-Met-Leu-Phe (fMLP) were investigated on human
      peripheral blood mononuclear cells. The selective phosphodiesterase IV
      inhibitors, rolipram and Ro 20-1724, and the non-selective phosphodiesterase
      inhibitor, theophylline, elicited a concentration-dependent inhibition of
      arachidonate release (EC50 = 1.3 x 10(-6) M, 3.2 x 10(-6) M and 3.7 x 10(-4) M
      respectively). The selective phosphodiesterase III inhibitor, milrinone (10(-5)
      M), only caused a slight effect while the phosphodiesterase V inhibitor,
      zaprinast (10(-5) M), the beta 2-adrenoceptor agonists, salbutamol and fenoterol
      (10(-5) M), failed to inhibit arachidonate release. Forskolin (10(-5) M) and
      N6,2'-O- dibutyryladenosine 3':5'-cyclic monophosphate (db-cAMP), 10(-3) M)
      elicited a moderate inhibition. Forskolin increased the effects of rolipram and
      Ro 20-1724 (EC50 = 4.5 10(-7) M and 4 x 10(-7) M respectively). Incubation of the
      cells with rolipram (10(-8) to 10(-5) M), Ro 20-1724 (10(-8) to 10(-5) M,
      forskolin (10(-5) M) or salbutamol (10(-5) M) alone, induced a moderate increase
      or no increase at all in intracellular cAMP. However, in the presence of
      forskolin, rolipram (10(-8) to 10(-6) M) and Ro 20-1724 (10(-8) to 10(-6) M)
      induced significant and concentration-dependent increase in intracellular levels
      of cAMP. These results suggest that the potent inhibition of arachidonate release
      from mononuclear cells by selective phosphodiesterase IV inhibitors may be due to
      increases in discrete pools of intracellular cAMP.

PMID- 8566181
TI  - Allosteric modulation of [3H]flunitrazepam binding to recombinant GABAA
      receptors.
AB  - The allosteric modulation of [3H]flunitrazepam binding by gamma-aminobutyric acid
      (GABA), pentobarbital, (+)-etomidate, etazolate, alphaxalone, propofol and
      chlormethiazole was investigated in cerebellar membranes and membranes from human
      embryonic kidney (HEK) 193 cells transfected with alpha 1 beta 3 gamma 2 or alpha
      1 gamma 2 subunits. Results obtained indicate that [3H]flunitrazepam binding to
      recombinant GABAA receptors consisting of alpha 1 beta 3 gamma 2 subunits could
      be modulated by these compounds in a way and with a potency similar to that
      observed in cerebellar membranes. In addition, it was demonstrated that not only
      receptors consisting of alpha 1 beta 3 gamma 3, but also those consisting of
      alpha 1 gamma 2 subunits exhibited [3H]flunitrazepam binding which could be
      stimulated by GABA. In contrast to alpha 1 beta 3 gamma 2 receptors, however,
      [3H]flunitrazepam binding to recombinant alpha 1 gamma 2 receptors was inhibited
      by pentobarbital, (+)-etomidate, etazolate, alphaxalone, propofol and
      chlormethiazole. This seems to indicate that binding sites for these compounds
      are present on alpha 1 gamma 2 receptors, but that their allosteric interaction
      with [3H]flunitrazepam binding sites is different from that of alpha 1 beta 3
      gamma 2 receptors.

PMID- 8566182
TI  - Prevention of mouse-rat brain xenograft rejection by a combination therapy of
      cyclosporin A, prednisolone and azathioprine.
AB  - Embryonic mouse hippocampal tissue was grafted as tissue blocks to the
      hippocampal region of adult rats and the effect of two different
      immunosuppressive treatments compared. Immunosuppression with cyclosporin A,
      prednisolone and azathioprine or with cyclosporin A alone was compared with
      placebo treatment. Eight weeks' postgrafting medication with cyclosporin A,
      prednisolone and azathioprine had resulted in survival of 14 out of 15 grafts
      (93%), compared with 11 out of 14 (79%) in the group treated with cyclosporin A
      alone. Only 2 out of 13 grafts (15%) survived in placebo-treated animals.
      Transplants in the trimedication group displayed distinct cell and neuropil
      layers and only minimal cellular infiltration by leukocyte common antigen
      expressing cells, whereas grafts in cyclosporin A- and placebo-treated groups
      were densely infiltrated. The results are discussed in relation to the need for
      extended immunosuppressive and antiinflammatory therapies after intracerebral
      grafting of histoincompatible tissues.

PMID- 8566183
TI  - Optical responses recorded after local stimulation in rat neostriatal slice
      preparations: effects of GABA and glutamate antagonists, and dopamine agonists.
AB  - Effects of GABA and glutamate antagonists as well as dopamine agonists and
      antagonists on the optical responses of neostriatal (Str) slices to local
      electrical stimulation were examined using a voltage-sensitive dye and a high
      speed image sensor. A single local stimulation applied to the Str slices evoked
      optical responses lasting for 40-80 ms and propagating in every direction up to
      about 1.5 mm. Bath application of bicuculline methiodide increased the intensity
      and duration of optical responses, while their spatial response patterns were
      unchanged. Bath application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)
      greatly reduced the late part of responses occurring about 4 ms after
      stimulation, but the early part of responses was unaffected by CNQX. The early
      part of the response was eliminated by application of tetrodotoxin. Bath
      application of N-methyl-D-aspartate antagonists, 3-(2-carboxypiperazin-4-yl)
      propyl-1-phosphonic acid and 2-amino-5-phosphonovaleric acid resulted in only
      small changes in the optical responses. Bath application of D1 agonist 6-chloro
      7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5,-tetrahydro-1H-3-benz aze pine
      hydrobromide consistently increased the intensity but decreased the speed of
      propagation and duration of the optical response. Bath application of D2 agonist
      quinpirole had no effect on the optical response. D1 antagonist SCH 23390 and D2
      antagonist sulpiride also failed to change optical responses. These results
      indicate that the early part of the response is due to direct activation of the
      neuronal elements by electrical stimulation, while the late part of the response
      is due mainly to glutamatergic ex-citatory postsynaptic potentials (EPSPs)
      mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA)/kainate receptors. This study also suggests that dopamine may modulate
      AMPA/kainate responses through D1 receptors.

PMID- 8566184
TI  - On-line compensation of gaze shifts perturbed by micro-stimulation of the
      superior colliculus in the cat with unrestrained head.
AB  - Prior studies have led to the gaze feedback hypothesis, which states that quick
      orienting movements of the visual axis (gaze shifts) are controlled by a feedback
      system. We have previously provided evidence for this hypothesis by extending the
      original study of Mays and Sparks (1980) to the cat with unrestrained head
      (Pelisson et al. 1989). We showed that cats compensated for a stimulation-induced
      perturbation of initial gaze position by generating, in the dark, an accurate
      gaze shift towards the remembered location of a flashed target. In the present
      study, we investigate goal-directed gaze shifts perturbed "in flight" by a brief
      stimulation of the superior colliculus. The microstimulation parameters were
      tuned such that significant perturbations were induced without halting the
      movement. The ambient light was turned off at the onset of the gaze shift,
      suppressing any visual feedback. We observed that, following stimulation offset,
      the gaze shift showed temporal and spatial changes in its trajectory to
      compensate for the transient perturbation. Such compensations, which occurred "on
      line" before gaze shift termination, involved both eye and head movements and had
      dynamic characteristics resembling those of unperturbed saccadic gaze shifts.
      These on-line compensations maintained gaze accuracy when the stimulation was
      applied during the early phase of large and medium (about 60 and 40 degrees)
      movements. These results are compatible with the notion of a gaze feedback loop
      providing a dynamic gaze error signal.

PMID- 8566186
TI  - Deficits in torsional and vertical rapid eye movements and shift of Listing's
      plane after uni- and bilateral lesions of the rostral interstitial nucleus of the
      medial longitudinal fasciculus.
AB  - The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)
      contains burst neurons whose activity precedes rapid eye movements with a
      vertical and/or torsional component. To ascertain their causal role in the
      generation of conjugate eye movements, we placed uni- and bilateral kainic acid
      lesions in that region. Unilateral inactivation of the riMLF leads to a loss of
      all rapid eye movements with an ipsitorsional component (ipsitorsional is defined
      as movement of the upper pole of the ipsilateral eye in a temporal direction).
      Vertical eye movements are impaired in an asymmetric way, with downward movements
      slowed and upward movements little affected. Listing's plane is shifted in the
      contratorsional direction, i.e., we find a constant torsional offset for all eye
      positions. With bilateral lesions one observes a total loss of all vertical and
      torsional eye movements, while Listing's plane retains its shape and position.
      These results show that burst neurons in the riMLF play a decisive role in
      generating rapid eye movements with a vertical and torsional component.

PMID- 8566185
TI  - Electrophysiological characterization of dopaminergic and non-dopaminergic
      neurones in organotypic slice cultures of the rat ventral mesencephalon.
AB  - The aim of the present study was to characterize electrophysiologically neurones
      in organotypic cultures of the rat ventral mesencephalon and to compare these
      results with results published for the same neurones in other types of
      preparation. Intracellular recordings were obtained in 3- to 8-week-old
      organotypic slice cultures of the ventral mesencephalon prepared from new-born
      rats. Dopaminergic neurones were distinguished from non-dopaminergic neurones by
      staining with the autofluorescent serotonin analogue 5,7-dihydroxytryptamine and
      briefly viewing the preparation with short exposures to ultraviolet (UV) light
      (365 nm). Short exposures to UV light did not affect the electrophysiological
      properties. There were no significant differences between dopaminergic and non
      dopaminergic neurones with regard to resting membrane potential or action
      potential threshold and amplitude, and in both types of neurone spontaneous burst
      activity and glutamatergic excitatory postsynaptic potentials were seen. There
      were differences in the following parameters, which can be used to distinguish
      between the two types of neurone. Dopaminergic neurones had broad action
      potentials (2-9 ms), high input resistance (mean 81 M omega), were silent or
      fired spontaneously at a low frequency (0-9 Hz), and no spontaneous GABAA-ergic
      inhibitory postsynaptic potentials or inward rectification were present. In
      contrast, non-dopaminergic neurones had fast action potentials (0.6-3.2 ms), low
      input resistance (mean 32 M omega), were silent or fired spontaneously at
      relatively high firing frequency (0-28 Hz), and sometimes inhibitory postsynaptic
      potentials and inward rectification were seen. In the presence of 1 microM
      tetrodotoxin and 10 mM tetraethylammonium, Ca2+ spikes could be evoked in both
      dopaminergic and non-dopaminergic neurones. Dopaminergic neurones in 3- to 8-week
      old organotypic slice cultures have a number of distinguishing
      electrophysiological characteristics similar to those recorded in other types of
      acute or cultured preparations. However, some intrinsic regulatory mechanisms,
      namely the slow oscillatory potentials, inward rectification and the K+ current,
      IA, seem to be missing in the cultured neurones.

PMID- 8566187
TI  - The recovery function of paired somatosensory evoked potentials in cerebral
      ischemic rabbits.
AB  - In cerebral ischemia of different degrees, the amplitudes of somatosensory evoked
      potentials (SEPs) are facilitated or depressed. Different mechanisms might be
      responsible for the explanation of the contradictory phenomena. SEPs obtained
      using the paired stimulation method were employed in trying to find out the role
      of the functional changes of the inhibitory system in the brain during ischemia.
      Eight rabbits were used for recording the amplitude recovery curve of paired SEPs
      in the normal state, and the other ten were used for recording the recovery curve
      in different cerebral ischemic degrees. Cerebral ischemia was induced by the iron
      particle injection method. The attenuation of the depressed recovery function of
      the paired SEP amplitudes was detected during cerebral ischemia when SEP
      amplitudes were either facilitated or depressed. The results indicate that the
      function of the inhibitory system in the brain is selectively vulnerable during
      cerebral ischemia.

PMID- 8566188
TI  - The nucleus accumbens in monkeys (Macaca fascicularis). III. Reversal learning.
AB  - The nucleus accumbens (NA), which receives inputs from limbic structures and
      projects to the motor system, may be important for the association of
      reinforcement with action. There are projections to the NA from the amygdala and
      hippocampus. Discrimination and reversal learning tasks which are known to be
      disrupted by lesions to these areas in monkeys were given to monkeys with lesions
      of the NA. Twelve monkeys (Macaca fascicularis) were used in the present study.
      Six of these received ibotenic acid lesions which resulted in considerable cell
      loss in the NA; the remaining six acted as controls. The first group of six
      monkeys were taught a visual discrimination task pre-operatively. Post
      operatively, these monkeys were tested on visual and spatial discrimination and
      reversal tasks. A second group of six monkeys were tested on a motor reversal
      task. The results indicate that ibotenic acid lesions of the NA transiently
      impair spatial but not visual reversal learning in monkeys. The NA lesions did
      not impair a monkey's ability to perform visual or spatial discriminations, or
      the ability to perform the motor learning or motor reversal tasks. Our results
      suggest that bilateral lesions of the NA in monkeys do not disrupt the ability to
      discriminate basic properties of reward-related stimuli or the formation of
      visual stimulus-reward associations. In addition, our results argue against
      theories which suggest that the NA is important for behavioural switching or
      general behavioural flexibility. We conclude that the NA may play a more specific
      role in the association of temporal and spatial cues with movement and reward.

PMID- 8566189
TI  - Long-term potentiation deficits and excitability changes following traumatic
      brain injury.
AB  - The effects of traumatic brain injury (TBI) on hippocampal long-term potentiation
      (LTP) and cellular excitability were assessed at postinjury days 2, 7, and 15.
      TBI was induced using a well-characterized central fluid-percussion model. LTP of
      the Schaffer collateral/commissural system was assessed in vivo in urethane
      anesthetized rats. Significant LTP of the population excitatory postsynaptic
      potential (EPSP) slope was found only in controls, and no recovery to control
      levels was observed for any postinjury time point. Four measurement parameters
      reflecting pyramidal cell discharges (population spike) indicated that TBI
      significantly increased cellular excitability at postinjury day 2: (1) pretetanus
      baseline recording showed that TBI reduced population spike threshold and
      latency; (2) tetanic stimulation (400 Hz) increased population spike amplitudes
      to a greater degree in injured animals than in control animals; (3) tetanus
      induced population spike latency shifts were greater in injured cases; and (4)
      tetanic stimulation elevated EPSP to spike ratios (E-S potentiation) to a greater
      degree in injured animals. These parameters returned to control levels, as
      measured on postinjury days 7 and 15. These results suggest that TBI-induced
      excitability changes persist at least through 2 days postinjury and involve a
      differential impairment of mechanisms subserving LTP of synaptic efficacy and
      mechanisms related to action potential generation.

PMID- 8566190
TI  - Visual movement and pattern are important for the development of a map of
      auditory space in the guinea pig superior colliculus.
AB  - Previous data have indicated that, if guinea pigs are deprived of all visual
      information during a crucial period early in development (26-30 days after
      birth), the map of auditory space in the superior colliculus (SC) is completely
      disrupted. In the experiments reported here, multi-unit auditory receptive fields
      were recorded in the SC of two groups of anaesthetised guinea pigs that had been
      exposed to different forms of visual deprivation. One group was reared in a
      movement-free environment (strobe-reared) and the other group was reared in a
      pattern-free environment (their eyes covered with light-diffusing masks). Both
      groups experienced visual restriction during the crucial period for auditory
      space map development. In both experimental groups, the multi-unit auditory
      receptive fields were broad and all spatial tuning parameter values were
      significantly greater than the equivalent values from a control group of normal
      animals. In the pattern- and motion-deprived groups, a significant correlation
      existed between the rostro-caudal position of the recording electrode in the SC
      and the peak response angle of the receptive field, thus showing a degree of
      topographic organisation of the auditory receptive fields in the SC. However, the
      topographic order was less precise than that displayed by the control group of
      animals. These results indicate that, during development, both visual pattern and
      movement are important for the refinement of the SC auditory space map in the
      guinea pig.

PMID- 8566191
TI  - Oxygen supply and ion homeostasis of the respiratory network in the in vitro
      perfused brainstem of adult rats.
AB  - An in vitro arterially perfused medulla preparation of 3- to 8-week-old rats is
      described in which synchronous rhythmic activity (frequency 4.5 +/- 1.7
      cycles/min, burst duration 3.1 +/- 1.1 s, n = 40) was recorded from hypoglossal
      (XII), vagal (X), or spinal (C1-2) nerves and from different classes of neurons
      in the region of the ventral respiratory group (VRG). Stimulation of dorsal X
      nerve rootlets produced a reversible blockade of rhythmic activity. Under steady
      state conditions, tissue oxygen (pO2) in the VRG (depth of 600-1600 microns below
      the ventral surface) fell from 180 to 40 mmHg. Extracellular K+ activity (aKe) in
      the VRG was about 0.3 mM higher, calcium concentration ([Ca]e) did not differ,
      and pH (pHe) was about 0.27 units lower than in the perfusion or superfusion
      solution (with an aKe of 2.2 mM, a [Ca]e of 1.5 mM and a pHe of 7.4). During
      inspiratory XII nerve discharges, rhythmic increases of aKe by up to 0.8 mM were
      detected in the VRG. Perfusion of N2-gassed hypoxic solutions (5-10 min) resulted
      in a tissue anoxia of the VRG and a reversible cessation of rhythmic activity
      after 2-7 min. Such anoxia was accompanied by a rise of aKe by up to 35 mM,
      whereas pHe and [Ca]e fell (from mean levels of 7.17 and of 1.5 mM, respectively)
      by more than 0.2 pH units and 1 mM. Similar observations were made during a 2- to
      5-min arrest of the perfusion pump to simulate ischaemia, whereas significantly
      larger changes in aKe, pHe and [Ca]e were revealed during an "ischaemia" period
      of 10 min. The results indicate that the rhythmic activity is generated by the
      functionally intact respiratory network of the VRG in which neurons are under
      aerobic conditions and ion homeostasis is not impaired. We conclude that the
      preparation is an appropriate in vitro model for the analysis of the cellular
      mechanisms for generation of respiratory rhythm and of metabolic perturbations
      like anoxia and ischaemia in the mature respiratory network.

PMID- 8566192
TI  - Dopaminergic neuronal survival and the effects of bFGF in explant, three
      dimensional and monolayer cultures of embryonic rat ventral mesencephalon.
AB  - Embryonic substantia nigra cells when transplanted into the striatum can reverse
      many of the defects of Parkinson's disease. The efficacy of such grafts is
      compromised by the poor survival of grafted dopaminergic neurones; typically, 3
      10% survive transplantation. We used three tissue culture models to identify
      stages in the procedure for the preparation and insertion of grafts which might
      be responsible for this cell death and to identify environments in which survival
      is optimised. (1) The ventral mesencephalon was dissected from the donor brain,
      then placed immediately into culture contained in a collagen gel. (2) The
      dissected tissue fragments were enzymatically dissociated, then the cells placed
      into monolayer culture. (3) Enzymatically dissociated tissue was packed into 0.5
      mm-diameter porous tubes, to simulate the compaction of cells into a graft
      deposit in the host brain. Dissociation of the tissue by itself caused the death
      of approximately 30% of dopaminergic neurones, as judged by the difference in
      cell counts between the intact embryonic day 14 (E14) mesencephalon, and cells
      dissociated then packed into tubes. Of the dissociated neurones approximately 60%
      died during the first 24 h and 87% during the first 3 days in monolayer culture,
      while only 7% of dopaminergic neurones in three-dimensional cultures and 11% of
      neurones in explant cultures died over the first 3 days. Embryonic dopaminergic
      neurones are clearly very vulnerable to adverse conditions during the first days
      after their removal from the donor brain. The excellent survival of neurones in
      three-dimensional and explant cultures indicates that close association with
      other cells, which may provide greatly improved access to trophic factors, can
      enable the cells to survive this period of vulnerability. In contrast to its
      effects in monolayer cultures, bFGF had no effect on dopaminergic neuronal
      survival in either explant or three-dimensional cultures.

PMID- 8566193
TI  - A correlogram analysis of the activity in the rostral ventromedial medulla of
      awake rats and in rats anesthetized with ketamine or pentobarbital following the
      administration of morphine.
AB  - The spiking activity of single units and their corresponding mass activity in the
      rostral ventromedial medulla (RVM) was recorded simultaneously in rats that were
      either awake or anesthetized with pentobarbital or ketamine. Autocorrelograms and
      cross-correlograms were calculated to illustrate the distribution of interspike
      intervals under each of these conditions. The spontaneous activity in both
      anesthetized groups, but not the awake group, displayed a low incidence for short
      intervals (about 1-36 ms) between spikes. However, this low incidence of short
      interspike intervals was found in some awake rats following the administration of
      subanesthetic dosages of ketamine, pentobarbital, or morphine. The occurrences,
      or lack of occurrences of these short interspike intervals may be a marker for
      the anesthetized state of the rat. A basal spiking pattern, as illustrated by
      three different types of correlograms, was observed, and these basal patterns did
      not usually change after the administration of morphine to awake or anesthetized
      rats, even though the cells became excited or inhibited. Cross-correlograms
      revealed that the synapses between "on" and "off" cells might sometimes be
      inhibitory, while at other times they might be excitatory; however, cells of the
      same class mainly shared excitatory connections. In summary, ketamine and
      pentobarbital do alter the firing patterns of individual neurons in the RVM, but,
      no matter what state the rat is in, the activity of individual RVM neurons is
      strongly related to the activity of other neurons in the local network.

PMID- 8566194
TI  - The role of motor action in anticipatory postural adjustments studied with self
      induced and externally triggered perturbations.
AB  - This study investigated the relation between the magnitude of a motor action
      triggering a postural perturbation and the magnitude of anticipatory postural
      adjustments. Subjects stood on a force platform and held, in extended arms, a
      balloon with a 2.2-kg load suspended on a rigid cord. In different series,
      unloadings were induced by fast bilateral shoulder abduction movements, by
      popping the balloon with a tack taped to the subject's right middle finger, or by
      the experimenter popping the balloon. Anticipatory postural adjustments were seen
      during all self-initiated unloadings as changes in the level of activation of
      postural muscles and in displacements of the center of pressure. However,
      absolute values of these changes were significantly smaller in the series with
      balloon popping as compared to the series with shoulder abductions. Such
      reactions were absent when the unloading was triggered by the experimenter. We
      conclude that a self-triggered perturbation is always associated with
      anticipatory postural adjustments, while the magnitude of the adjustments may be
      scaled with respect to the magnitude of a motor action used to induce the
      perturbation.

PMID- 8566196
TI  - Short-term adaptation of the phase of the vestibulo-ocular reflex (VOR) in normal
      human subjects.
AB  - We investigated the effects of short-term vestibulo-ocular reflex (VOR)
      adaptation on the gain and phase of the VOR, and on eccentric gaze-holding in
      darkness, in five normal human subjects. For 1 h, subjects sat in a chair that
      rotated sinusoidally at 0.2 Hz while surrounded by a visual stimulus (optokinetic
      drum). The drum was rotated relative to the chair, to require a VOR with either a
      phase lead or lag of 45 deg (with respect to a compensatory phase of zero) with
      no change in gain, or a gain of 1.7 or 0.5 with no change in phase. Immediately
      before and after each training session, VOR gain and phase were measured in the
      dark with 0.2 Hz sinusoidal rotation. Gaze-holding was evaluated following 20 deg
      eccentric saccades in darkness. Adaptation paradigms that called only for a phase
      lead produced an adapted VOR with 33% of the required amount of phase change, a
      20% decrease in VOR gain, and an increased centripetal drift after eccentric
      saccades made in darkness. Adaptation paradigms that called for a phase lag
      produced an adapted VOR with 29% of the required amount of phase change, no
      significant change in VOR gain, and a centrifugal drift after eccentric saccades.
      Adaptation paradigms requiring a gain of 1.7 produced a 15% increase in VOR gain
      with small increases in phase and in centripetal drift. Adaptation paradigms
      requiring a gain of 0.5 produced a 31% decrease in VOR gain with a 6 deg phase
      lag and a centrifugal drift. The changes in drift and phase were well correlated
      across all adaptation paradigms; the changes in phase and gain were not. We
      attribute the effects on phase and gaze-holding to changes in the time constant
      of the velocity-to-position ocular motor neural integrator. Phase leads and the
      corresponding centripetal drift are due to a leaky integrator, and phase lags and
      the corresponding centrifugal drift are due to an unstable integrator. These
      results imply that in the short-term adaptation paradigm used here, the control
      of drift and VOR phase are tightly coupled through the neural integrator, whereas
      VOR gain is controlled by another mechanism.

PMID- 8566195
TI  - Volitional control of anticipatory ocular pursuit responses under stabilised
      image conditions in humans.
AB  - Ocular pursuit responses have been examined in humans in three experiments in
      which the pursuit target image has been fully or partially stabilised on the
      fovea by feeding a recorded eye movement signal back to drive the target motion.
      The objective was to establish whether subjects could volitionally control smooth
      eye movement to reproduce trajectories of target motion in the absence of a
      concurrent target motion stimulus. In experiment 1 subjects were presented with a
      target moving with a triangular waveform in the horizontal axis with a frequency
      of 0.325 Hz and velocities of +/- 10-50 degrees/s. The target was illuminated
      twice per cycle for pulse durations (PD) of 160-640 ms as it passed through the
      centre position; otherwise subjects were in darkness. Subjects initially tracked
      the target motion in a conventional closed-loop mode for four cycles. Prior to
      the next target presentation the target image was stabilised on the fovea, so
      that any target motion generated resulted solely from volitional eye movement.
      Subjects continued to make anticipatory smooth eye movements both to the left and
      the right with a velocity trajectory similar to that observed in the closed-loop
      phase. Peak velocity in the stabilised-image mode was highly correlated with that
      in the prior closed-loop phase, but was slightly less (84% on average). In
      experiment 2 subjects were presented with a continuously illuminated target that
      was oscillated sinusoidally at frequencies of 0.2-1.34 Hz and amplitudes of +/- 5
      20 degrees. After four cycles of closed-loop stimulation the image was stabilised
      on the fovea at the time of peak target displacement. Subjects continued to
      generate an oscillatory smooth eye velocity pattern that mimicked the sinusoidal
      motion of the previous closed-loop phase for at least three further cycles. The
      peak eye velocity generated ranged from 57-95% of that in the closed-loop phase
      at frequencies up to 0.8 Hz but decreased significantly at 1.34 Hz. In experiment
      3 subjects were presented with a stabilised display throughout and generated
      smooth eye movements with peak velocity up to 84 degrees/s in the complete
      absence of any prior external target motion stimulus, by transferring their
      attention alternately to left and right of the centre of the display. Eye
      velocity was found to be dependent on the eccentricity of the centre of attention
      and the frequency of alternation. When the target was partially stabilised on the
      retina by feeding back only a proportion (Kf = 0.6-0.9) of the eye movement
      signal to drive the target, subjects were still able to generate smooth movements
      at will, even though the display did not move as far or as fast as the eye. Peak
      eye velocity decreased as Kf decreased, suggesting that there was a continuous
      competitive interaction between the volitional drive and the visual feedback
      provided by the relative motion of the display with respect to the retina. These
      results support the evidence for two separate mechanisms of smooth eye movement
      control in ocular pursuit: reflex control from retinal velocity error feedback
      and volitional control from an internal source. Arguments are presented to
      indicate how smooth pursuit may be controlled by matching a voluntarily initiated
      estimate of the required smooth movement, normally derived from storage of past
      re-afferent information, against current visual feedback information. Such a
      mechanism allows preemptive smooth eye movements to be made that can overcome the
      inherent delays in the visual feedback pathway.

PMID- 8566197
TI  - Head and trunk movements in the frontal plane during complex dynamic equilibrium
      tasks in humans.
AB  - Eight normal human subjects were asked to maintain monopodal equilibrium on a
      narrow beam (task 1) or bipodal equilibrium on an unstable rocking platform (task
      2) for 5 s. Each task was performed under four experimental conditions: (1) in
      light, (2) in darkness, (3) in light while subject had to hold a full cup of
      water, and (4) as in 3, but with additional instructions to fix the gaze on the
      cup. The movements of the trunk and head in the frontal plane were recorded by
      means of a 50-Hz TV image analyzer that computed the coordinates of small
      reflective markers glued on the skin of the subjects. On the beam the trunk was
      inclined on the side of the supporting foot (13 +/- 9 degrees), on the rocking
      platform the mean trunk orientation during the tests was nearly vertical (2 +/- 7
      degrees). Nevertheless, in both tasks the mean head position was the same and
      close to vertical: 1.5 +/- 4 degrees on the rocking platform and 1.5 +/- 5
      degrees on the beam. For both tasks and all experimental conditions the head
      remained stabilized relative to vertical, despite large translations in the
      frontal plane. Standard deviations of head orientation from its mean value were
      2.8 +/- 2 degrees for task 1 and 2 +/- 1.5 degrees for task 2. The changes of
      trunk orientation were significantly higher: 6.2 +/- 4.8 degrees and 4.5 +/- 4
      degrees, respectively. The differences in angular stability of head and trunk,
      measured through the standard deviations of angular displacements, were
      especially pronounced in trials with large trunk movements. It was concluded that
      head angular stabilization, providing the central nervous system with necessary
      visual and vestibular references, is essential for effective dynamic postural
      control in the frontal plane during complex equilibrium tasks.

PMID- 8566198
TI  - Programming the duration of a motor sequence: role of the primary and
      supplementary motor areas in man.
AB  - Event-related potentials were recorded in a reaction time (RT) paradigm, where
      the duration of a learned interval (either 0.7 s or 2.5 s) delimited by two brief
      button-presses was to be accurately controlled. A preparatory signal (PS) either
      did not give or gave prior information concerning the duration of the following
      response (neutral condition or primed conditions, respectively). In the latter
      case, the information was either validated (valid condition) or invalidated
      (invalid condition) by the response signal (RS). When duration was not known in
      advance (invalid and neutral conditions), RTs were longer before a response of
      short than long duration. This difference was not found under the valid
      condition. During the preparatory period (PP), the amplitude of the contingent
      negative variation (CNV) was larger when the duration was primed than when it was
      not. A larger CNV appeared when the PS primed a short rather than a long
      duration. This effect occurred in the early part of the PP over the supplementary
      motor area (SMA) and in its latest part over the primary motor area (MI). The RT
      and the electrophysiological pattern were interpreted as revealing the occurrence
      of programming operations regarding the temporal dimension of the response. The
      time course of the CNV over the SMA and MI suggested that these two areas were
      hierarchically organized. Between the RS and the onset of the response,
      differences probably related to programming effects were still found over MI: the
      activities were larger under the valid than under the neutral condition. However,
      no sign of deprogramming (expected in the invalid condition) was observed:
      similar amplitudes were found under the neutral and invalid conditions.
      Deprogramming operations seemed to be postponed during response execution where
      the invalid condition evoked larger activities than the two other conditions over
      the SMA. Finally, MI but not the SMA yielded a Bereitschaftpotential before the
      second press ending the response (i.e., during response execution). These results
      suggest that the duration of a motor response can be a part of the motor program
      and that the SMA plays a major role in programming processes but not in response
      execution, contrary to MI.

PMID- 8566199
TI  - Somatotopical projections from the supplementary motor area to the red nucleus in
      the macaque monkey.
AB  - Direct projections from the supplementary motor area (SMA) to the red nucleus
      were investigated in the Japanese monkey (Macaca fuscata). The anterograde
      tracer, horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP), was
      injected into various regions of the SMA after intracortical microstimulation
      mapping. After WGA-HRP injection into the orofacial, forelimb, or hindlimb region
      of the SMA, anterogradely labeled axon terminals were found, respectively, in the
      medial, intermediate, or lateral portion of the parvocellular part of the red
      nucleus, bilaterally with an ipsilateral predominance. The results indicate the
      clear somatotopical arrangement of corticorubral projections from the SMA.

PMID- 8566201
TI  - Regeneration of respiratory pathways within spinal peripheral nerve grafts.
AB  - Central respiratory neurons exhibit normal activity after axonal regeneration
      within blind-ended peripheral nerve grafts (PNGs) inserted near the corresponding
      cell bodies in the medullary respiratory centers. Part of these medullary
      respiratory neurons project toward the spinal cord and contribute to descending
      respiratory pathways that control respiratory motoneurons. The present work
      investigates to what extent cervical respiratory pathways could be directed out
      of the central nervous system within PNGs inserted distant to the medullary
      respiratory nuclei. In adult rats (n = 13), autologous segments of the peroneal
      nerve were implanted into the ventrolateral part of the C2 spinal cord at the
      level of the descending respiratory pathways. Two to four months after grafting,
      electrophysiological recording of teased graft filaments (n = 562) revealed the
      presence of regenerated nerve fibers with unitary impulse traffic (n = 164) in
      all tested PNGs (n = 6). Respiratory discharges (n = 52) corresponded to efferent
      and afferent activity. Efferent respiratory discharges (n = 32) originated from
      central respiratory neurons which remained functional and preserved afferent
      connections. Retrograde horseradish peroxidase labeling applied to the distal cut
      end of PNGs (n = 7) revealed stained (42/1997) neurons in areas where respiratory
      cells have been described. Afferent respiratory discharges (n = 20) were
      synchronized with lung inflation but their origin (stretch pulmonary receptors
      and/or respiratory muscle receptors) was not determined. On the basis of
      additional data from light and electron microscopy of PNGs, comparison was made
      between anatomical, retrograde labeling, and electrophysiological data. The main
      conclusion is that spinal PNGs appear to be able to promote axonal regeneration
      of functional respiratory efferent and afferent pathways.

PMID- 8566200
TI  - Potentiation of amphetamine-induced locomotor activity following NMDA-induced
      retrohippocampal neuronal loss in the rat.
AB  - The present experiment assessed the locomotor response to a low dose (1 mg/kg) of
      systemic D-amphetamine in rats with cytotoxic lesions of the retrohippocampus
      (entorhinal and extra-subicular cortices), compared with vehicle-operated shams
      and unoperated controls. Under spontaneous and saline conditions, both the sham
      and the lesioned animals were more active than unoperated controls, and they did
      not differ from each other. Systemic D-amphetamine produced increased locomotion
      in all groups, but this effect was potentiated in animals with retrohippocampal
      lesions; two control groups did not differ from each other in their response to
      the drug. The present results are consistent with the suggestion that cell loss
      within the retrohippocampal region could affect the functional response of
      nucleus accumbens to amphetamine. The results are discussed in terms of the
      interaction between the retrohippocampus and nucleus accumbens in the control of
      mesolimbic dopamine release and the possible implications for schizophrenia.

PMID- 8566202
TI  - BDNF enhances the functional reinnervation of the striatum by grafted fetal
      dopamine neurons.
AB  - Transplantation of fetal dopaminergic neurons to the striatum can ameliorate
      neurological deficits exhibited by experimental animals and human graft
      recipients with Parkinson's disease. Recovery, however, is incomplete due to
      suboptimal survival of grafted cells and limited synaptic integration with the
      host brain. A number of neurotrophic factors have recently been shown to promote
      the survival and differentiation of dopamine neurons in vitro. In the present
      study we examined the effects of one such factor, brain-derived neurotrophic
      factor (BDNF), on the development of fetal substantia nigra following
      transplantation to the dopamine-depleted striatum of adult rats. Infusion of BDNF
      greatly enhanced the reinnervation of the host striatum by the engrafted dopamine
      neurons, as determined by tyrosine hydroxylase immunostaining, and also increased
      the effect of the graft on locomotor behavior induced by amphetamine
      administration. These effects became apparent during the 4-week period of BDNF
      infusion and persisted for an additional 6 weeks following the termination of
      BDNF delivery. These findings demonstrate that BDNF exerts a significant effect
      on the functional reinnervation of the striatum by transplanted fetal dopamine
      neurons in the rat, and suggest that application of this factor might similarly
      improve the clinical efficacy of neural transplantation employed in the treatment
      for Parkinson's disease.

PMID- 8566203
TI  - Amelioration of functional deficits from spinal cord trauma with systemically
      administered NBQX, an antagonist of non-N-methyl-D-aspartate receptors.
AB  - Excitatory amino acid (EAA) receptors play a significant role in delayed neuronal
      death after ischemic and traumatic injury to the CNS. Recent data based on focal
      microinjection experiments have demonstrated that 2,3-dihydro-6-nitro-7-sulfamoyl
      benzo(f)quinoxaline (NBQX), a highly selective and potent antagonist of non-N
      methyl-D-aspartate ionotropic EAA receptors, i.e., those preferring alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or kainate, can reduce
      histopathology and functional deficits after traumatic spinal cord injury (SCI).
      Thus, non-NMDA receptors at or near the injury site appear to be important in
      secondary injury processes that contribute significantly to the consequences of
      SCI. We have now examined the effects of systemic NBQX, using intravenous
      infusion, the most commonly used and temporally efficient clinical mode of drug
      administration. Standardized contusive SCI was produced at the T8 vertebral level
      in Sprague-Dawley rats. Beginning at 15 min postin-jury, NBQX was administered
      intravenously at 1 mg/kg/min for 30 min. Behavioral tests of hindlimb functional
      deficits were performed at 1 day and weekly for 1 month after SCI. Spinal cord
      tissue was then examined morphometrically to compare lesion size and amount of
      spared tissue. We found that intravenous administration of NBQX significantly
      reduced functional impairment after SCI. The effects included more rapid and
      extensive recovery of hindlimb reflexes, more rapid establishment of a reflex
      bladder, and a more rapid and greater degree of recovery of coordinated use of
      hindlimbs in open field locomotion, swimming, and maintaining position on an
      inclined plane. The profile of effects was similar to that seen with focal
      microinjection of NBQX, suggesting that even with systemic administration, the
      drug acts mainly at the injury site. Further, the results support a therapeutic
      potential for NBQX, or similar drugs that antagonize non-NMDA receptors and
      inhibit secondary injury processes after SCI.

PMID- 8566204
TI  - Use of fetal cortical grafts in hypoxic-ischemic brain injury in neonatal rats.
AB  - In view of numerous studies demonstrating that intracerebral implants of fetal
      neural tissue can promote functional recovery and structural repair in the
      damaged brain, the present study examined the potential use of neocortical
      transplantation in newborn rats that sustained hypoxic-ischemic brain injury.
      Ischemic insult was induced in Long-Evans, black-hooded 1-week-old rats by
      unilateral common carotid artery occlusion followed by 2.5 h of hypoxia in 8% O2.
      One week later, animals received neocortical block transplants. At 2-6 weeks
      posttransplantation, animals were sacrificed and their brains examined
      histologically. Transplants survived in over 80% of the animals and the presence
      of acetylcholinesterase-positive fibers crossing the host-transplant interface
      provided evidence of transplant integration with the host brain. However,
      morphometric measurements revealed that the transplants were unable to reduce the
      hypoxia-ischemia-induced degeneration in the host hippocampus, caudate-putamen,
      or thalamus. Nonetheless the demonstrated survival of grafts in the neonatal
      hypoxia-ischemia model suggests a potential therapeutic effect.

PMID- 8566205
TI  - Extrinsic inhibitory innervation to rubral neurons in rat brain-stem slices.
AB  - Synaptic connections between the neurons in the red nucleus (RN) and its
      extrinsic neurons were studied using rat brain-stem slices. Intracellular records
      were obtained from the RN neurons. Ipsilateral stimuli to areas in the
      dorsolateral mesencephalic reticular formation (DLMRF) or substantia nigra (SN)
      elicited monosynaptic hyperpolarizing postsynaptic potentials (PSPs) in about 95%
      of RN neurons recorded. The hyperpolarizing PSPs could be reversibly blocked by
      bicuculline, indicating that they were GABAA receptor-mediated-Cl(-)-inhibitory
      PSPs. The sites of most inhibitory synapses arising from DLMRF and SN are
      possibly located on the proximal half of the soma-dendritic membrane of RN
      neurons, according to the analysis of the IPSPs with Rall's model. In addition,
      tracing dyes were employed to examine the morphological pathways. After rhodamine
      B, a retrograde tracer, was applied to the RN in brain slices, the cell bodies of
      a number of neurons in DLMRF and SN were labeled. These labeled neurons were also
      immunopositive for glutamic acid decarboxylase (GAD) as revealed from double
      labeling with an anti-GAD antiserum. The anterograde tracer, tetramethylrhodamine
      dextran, was applied to the DLMRF or SN and taken up by many neurons in the
      areas. A portion of these cells extended their processes toward and terminated
      within the RN. Moreover, electron microscopic examination confirmed that the
      tetramethylrhodamine dextran-decorated synaptic terminals were present in the RN.
      The results indicate that the rubral neurons receive direct GABAA receptor
      mediated inhibitory inputs from neurons in the DLMRF and SN, which may
      participate in modulation of rubral outputs.

PMID- 8566206
TI  - Ontogeny of human striatal DARPP-32 neurons in fetuses and following xenografting
      to the adult rat brain.
AB  - After a number of reports indicating positive clinical outcome of intrastriatal
      transplantation of fetal ventral mesencephalic tissue into patients with
      Parkinson's disease, the time may have come to consider the possibility of using
      this technique to treat patients with Huntington's disease. On the basis of the
      available literature, the Network of European CNS Transplantation and Restoration
      has established a program aiming at defining the optimal conditions for such
      clinical trials. The present study, conducted within this framework, pursued the
      goal of providing information concerning the period of striatal neuronal ontogeny
      in humans, taking into account the technical and legal requirements imposed by
      the clinical procedure of neural transplantation using human tissue. On this
      basis, it aimed at establishing a reliable dissecting method for the
      intrastriatal grafting of human fetal striatal neurons. The ontogeny of medium
      spiny neurons within the developing striatum was first studied in a series of
      human fetal brains, 5 to 10 weeks postconception, using immunocytochemical
      detection of DARPP-32. Immunoreactive neurons were observed in fetuses at 7 weeks
      of age and older. They were mostly localized in clusters, packed in the lateral
      ganglionic eminence. Over a 2-week-long period, DARPP-32 neurons increased in
      number. Their morphology remained poorly differentiated, however, with small cell
      bodies, few branched dendrites, and variable intensity of immunostaining. Based
      on these findings, selective dissection of the lateral ganglionic eminence was
      carried out. This tissue was stereotaxically implanted into the striatum of
      immunosuppressed adult rats previously lesioned. Two months postgrafting, DARPP
      32 neurons were observed as discrete patches, embedded within areas of
      essentially DARPP-32-negative tissue. Up to 2 months after grafting, neurons
      remained poorly differentiated in general, with only a few neurons exhibiting a
      dense immunoreactivity and long processes. These results indicate that striatal
      DARPP-32-immunoreactive neurons are present in the lateral ganglionic eminence in
      fetuses as soon as 7 weeks postconception. The striatal tissue can be dissected
      out and successfully transplanted. Within the grafts, neuronal differentiation
      appears to be a very long process, suggesting that many months might be necessary
      for these neurons to become functionally integrated into an adult host brain.

PMID- 8566207
TI  - Dose-response study of dehydroepiandrosterone sulfate on dentate gyrus long-term
      potentiation.
AB  - Neurosteroids are produced peripherally by endocrine glands, as well as
      enzymatically in the glia from steroid hormone substrates. GABA receptor sites
      and Ca2+ channel currents are prime targets for neurosteroid actions, and their
      effects are concentration dependent. For this reason, and the fact that treatment
      with one of them, sulfated dehydroepiandrosterone (DHEAS), improves performance
      in tasks involving memory in aged rats, we explored the effect of this hormone on
      dentate gyrus long term potentiation (LTP) in a dose-response mode. Intact
      anesthetized rats (urethane, 1.5 g/kg) were used. Electrodes were stereotaxically
      positioned in the perforant path and dentate gyrus for stimulation (bifocal) and
      recording (monofocal). DHEAS (10, 20, and 30 mg/kg, dissolved in Nutralipid 10%)
      was injected into the femoral vein. Ten animals were used to study the effects of
      each dose, one injection per animal. Twenty control animals were randomly
      interspersed within the experimental groups and were injected solely with
      Nutralipid. The results showed a significant increase in LTP at all doses in
      relation to baseline values. Further, there were significant increments in
      amplitude at 20 and 30 mg in relation to 10 mg. However, the data did not reveal
      significant differences between the 20- and the 30-mg-treated rats. Results are
      discussed in terms of effects of DHEAS on neurotransmitter and Ca2+ channel ion
      systems.

PMID- 8566208
TI  - Nerve growth factor delivery by gene transfer induces differential outgrowth of
      sensory, motor, and noradrenergic neurites after adult spinal cord injury.
AB  - Several neurotrophic factors have been identified that influence neuronal
      populations during central nervous system development, maturation, and
      senescence. To examine the responsiveness of the intact and the lesioned adult
      mammalian spinal cord to neurotrophic factors, primary rat fibroblasts were
      genetically modified to produce and secrete human nerve growth factor (NGF).
      These NGF-producing cells were then grafted to nonlesioned or lesioned adult rat
      spinal cords for periods of up to 1 year in vivo. Robust outgrowth of sensory and
      noradrenergic neurites was elicited by grafts in the previously nonlesioned
      spinal cord. Equally robust growth of sensory and noradrenergic neurites was
      observed in the lesioned spinal cord; in addition, partial sprouting of local
      motor neurites was elicited in the lesioned spinal cord. Thus, multiple neuritic
      populations of the adult spinal cord respond to neurotrophic factors by extending
      neurites, and this responsiveness is maintained and extended after major injury.
      Nerve growth factor delivered by somatic gene transfer may be a useful means of
      promoting axon regrowth in the injured spinal cord.

PMID- 8566209
TI  - Influence of physical parameters of nerve chambers on peripheral nerve
      regeneration and reinnervation.
AB  - We compared reinnervation of target organs after sciatic nerve section leaving
      gaps of 2, 4, 6, or 8 mm or gaps repaired with silicone tubes in different groups
      of mice. Functional reinnervation was assessed by noninvasive methods to
      determine recovery of sweating, nociceptive, and muscular functions in the
      hindpaw repeatedly during 3 months postoperation. The increase of gap length
      between nerve stumps delayed the beginning and reduced the degree of functional
      recovery achieved either with or without repair. When lesions were left
      unrepaired, functional reinnervation was only noticeable with a 2-mm gap and
      practically absent with longer gaps. With tube repair, reinnervation started
      earlier and achieved higher values than in the corresponding unrepaired groups.
      Tubulization was most effective with 4-mm gaps and comparatively less with
      shorter and longer gaps. With 4-mm gaps, recovery was higher when the silicone
      tube had a cross-sectional area 2.5 times that of the sciatic nerve than with
      narrower or wider tubes and when the wall was the thinnest available. In all
      cases muscle reinnervation showed a lower progression than sweating and
      nociceptive recovery.

PMID- 8566210
TI  - Dendrite bundles in motoneuronal pools of trunk and extremity muscles in the rat.
AB  - The anatomical distribution and the content of dendrite bundles were studied in
      the spinal cord of adult rats. We injected retrogradely transported Cholera Toxin
      subunit B into muscles in order to label motoneurons and their dendrites. Twenty
      one muscles in the trunk and in extremities were selected which are involved in a
      variety of motor tasks. Reconstructions were made from consecutive sections and
      the organization of dendrites was studied. In addition, the distributions of
      fiber types in the muscles were estimated on the basis of ATPase and succinic
      dehydrogenase-stained sections. Dendrite bundles are confined to pools of muscles
      which have postural tasks. Two different types can be distinguished. In the first
      type, longitudinal dendrite bundles extend over the length of the pool and also
      transversal bundles occur. Such pools innervate the axial musculature, and the
      soleus and flexor carpi ulnaris muscles in the extremities. These muscles contain
      relatively high percentages of slow twitch type I muscle fibers. In the second
      type, the occurrence of bundles is confined to a few zones within the pool. Such
      pools innervate muscles which are involved in postural tasks but in addition they
      also subserve other movement tasks. Distinct regions within these muscles are
      characterized by high percentages of type I muscle fibers.

PMID- 8566211
TI  - A herpes simplex virus vector overexpressing the glucose transporter gene
      protects the rat dentate gyrus from an antimetabolite toxin.
AB  - The use of herpes simplex virus vectors offers an attractive means for the in
      vitro and in vivo transfer of novel genes into postmitotic neurons. Such an
      approach allows for the introduction of genes with the potential to protect
      neurons from necrotic insults. Toward that end, we have previously constructed a
      bicistronic herpes viral vector expressing the gene for the Glut-1 rat brain
      glucose transporter (GT), along with the Escherichia coli lacZ reporter gene. We
      observed that this vector enhances glucose uptake both in primary hippocampal
      cultures and in the hippocampus itself. Moreover, we have found that this vector
      will protect a variety of types of cultured neurons from necrotic insults and
      protect hippocampal neurons in vivo from seizure-induced damage. In the present
      report, we further demonstrate the neuroprotective potential of this GT
      expressing vector. 3-Acetylpyridine, an electron transport uncoupler which is
      preferentially toxic to the dentate gyrus, was microinfused into the dorsal
      hippocampus of rats. Infection of dentate neurons with GT vectors at the time of
      exposure to the toxin significantly decreased damage, whereas infection with a
      physiologically neutral control vector did not. Moreover, there was a window of
      opportunity for this intervention, as microinfusion of the GT-expressing vector
      up to 1 h, but not 4 h, after the insult was still neuroprotective.

PMID- 8566212
TI  - Reactive astroglia support primary dendritic but not axonal outgrowth from mouse
      cortical neurons in vitro.
AB  - Reactive astrocytes are thought to be impediments to axon regrowth following
      injury to the mammalian central nervous system. Axon and dendrite growth,
      however, appear to be differently controlled by normal astrocytes in vitro. To
      determine whether reactive astrocytes differ in their ability to support axons or
      dendrites, embryonic (E18) mouse cortical neurons were cocultured with P4 and P12
      rat astroglial cells derived from normal or lesioned cortex. After 5 days in
      vitro, axon and dendrite outgrowth from isolated neurons was quantified with
      double-labeling immunohistochemical techniques. Reactive astrocytes were able to
      maintain primary dendrite growth, principally primary dendrite number. Axon
      elongation, however, was significantly reduced on both neonatal and more mature
      reactive astrocytes. These results indicate that reactive astrocytes may exhibit
      separate mechanisms to control dendrite and axon growth.

PMID- 8566213
TI  - ARL-15896, a novel N-methyl-D-aspartate receptor ion channel antagonist:
      neuroprotection against mitochondrial metabolic toxicity and regional
      pharmacology.
AB  - ARL-15896 [(+)-alpha-phenyl-2-pyridineethanamine], formerly known as FPL-15896,
      is a novel N-methyl-D-aspartate (NMDA) receptor ion channel antagonist. Using
      quantitative receptor autoradiography, we examined the regional binding
      characteristics of ARL-15896 and compared them to those of MK-801, the
      prototypical NMDA receptor channel blocker. The affinity of ARL-15896 was much
      lower (3000-fold) than that of MK-801 in all brain regions examined. In addition,
      in contrast to MK-801, which has a higher affinity in the forebrain than in the
      cerebellum (IC50 of 10 nM vs 24 nM), ARL-15896 had a higher affinity in the
      cerebellum than in the forebrain (IC50 of 17 microM vs 45 microM). The
      neuroprotective potential of ARL-15896 was investigated in a rat model of
      excitotoxicity, the intrastriatal injection of malonate. Malonate is a
      competitive inhibitor of succinate dehydrogenase, and its toxicity has been shown
      to be mediated largely by the NMDA receptor. Administration of ARL-15896 either
      intrastriatally (200 nmol) or subcutaneously (9.0 mg/kg) reduced the volume of
      the lesion produced by 1 mumol of malonate by 80%, a degree similar to that
      reported for MK-801. ARL-15896 was also protective when administered after the
      malonate injection. Furthermore, in contrast to MK-801, administration of ARL
      15896 was not associated with any apparent behavioral side effects. This report
      is consistent with previous studies suggesting that drugs with regional
      pharmacological profiles similar to that of ARL-15896 have better clinical
      tolerability; it also indicates that ARL-15896 is an effective neuroprotective
      agent.

PMID- 8566214
TI  - An experimental model of cerebral microischemia in rabbits.
AB  - Multiinfarct dementia is the second most common form of dementia in the elderly.
      An animal model of microischemia may provide information about the
      pathophysiology relevant when searching for prevention or treatment of
      microinfarctions in humans. The purpose of the present study was to develop an
      experimental model useful for studying discrete microischemic foci. In order to
      achieve single cerebral microischemic foci plastic beads with diameters of about
      100 microns were injected into the left heart ventricle of anesthetized rabbits.
      2-Deoxy-[14C]glucose (2-DG) and autoradiography were used to detect regions with
      disturbed metabolism. The tissue sections were inspected for impacted beads. Foci
      with markedly increased 2-DG accumulation and with diameters of about 1 mm were
      detected in all parts of the brain, indicating hypoxic regions with enhanced
      glycolysis. In some foci, located mainly in the basal ganglia, a central dip in
      the 2-DG profile was seen, suggesting poor glucose supply to the central ischemic
      region. The ratio foci/beads was about 1 in the brain stem (diencephalon
      included) and about 0.5 in the cortex. Twenty-four hours after embolization,
      infarctions, mainly in the deeper brain regions, were seen. There were still foci
      with increased 2-DG uptake, which were mainly located in the cortex. The results
      suggest that microemboli reaching the deeper brain regions give rise to metabolic
      disturbances more often than emboli reaching the cortex and that the ischemic
      foci in deeper brain regions are more prone to develop further into infarctions.

PMID- 8566215
TI  - Adrenal medullary implants reduce transsynaptic degeneration in the spinal cord
      of rats following chronic constriction nerve injury.
AB  - Peripheral nerve injury causes abnormal sensory processing, possibly due in part
      to neuroplastic changes in the CNS. Following chronic constriction injury of the
      sciatic nerve, transsynaptic degeneration is suggested by the presence of "dark
      neurons" found in superficial laminae of spinal cord. Previous studies in our
      laboratory have shown that grafts of adrenal medullary cells into the spinal
      subarachnoid space can reduce abnormal pain due to peripheral nerve injury. A
      possible mechanism for these beneficial effects is the reduction or interruption
      of excitotoxic events that lead to pathological CNS changes. In order to examine
      this, 2 weeks after unilateral sciatic nerve ligation using a chronic
      constriction injury model, animals received either adrenal medullary or control
      striated muscle tissue implanted in the lumbar subarachnoid space. Control
      striated muscle-transplanted animals with nerve injury displayed thermal
      hyperalgesia and elevated numbers of dark neurons in the superficial dorsal horn,
      compared to intact animals. These dark neurons were increased bilaterally, but
      predominantly ipsilaterally, to nerve injury. In contrast, in animals with
      adrenal medullary transplants, reduced numbers of dark neurons were found in
      parallel with reduced hyperalgesia. The low numbers of dark neurons in these
      animals were similar to age-matched unoperated controls. Two months after nerve
      ligation, dark neurons were not found in animals with nerve injury, although
      abnormal ruffled-appearing neurons were still present in untransplanted animals,
      suggesting partial recovery of damaged spinal neurons. The results of this study
      suggest that spinal adrenal medullary transplants can attenuate the
      neuropathological events perpetuating nerve-injury-induced pain by enhancing
      recovery of spinal neurons from excitotoxic insult.

PMID- 8566216
TI  - Functional and morphological restoration of intracranial brachial lesion of the
      retinocollicular pathway by peripheral nerve autografts in adult hamsters.
AB  - Axons of adult mammals can regenerate through peripheral nerve grafts and restore
      the retinocollicular pathway if lesioned proximal to the retinal ganglion cell
      somata. Whether the grafting and subsequent reinnervation of the superior
      colliculus (SC) is possible in distal axotomy in the brain is a question of
      clinical relevance. We have deafferented the SC of adult hamsters at its brachium
      thus axotomizing the retinal ganglion cell axons rostral to its synaptic contact
      with the SC neurons. After unilateral brachium transection, a short segment of
      the autologous sciatic nerve was grafted to bridge the lesioned site to the SC (n
      = 28). As controls the brachium was transected and left ungrafted (n = 12).
      Functional restoration was examined 3 to 75 weeks later in grafted (n = 16) and
      control (n = 5) animals by recording visual evoked responses from the collicular
      cells. Prior to recording the grafts were visually evaluated and categorized into
      successfully (n = 8) and unsuccessfully (n = 8) grafted groups. To diffuse flash
      stimuli applied to the contralateral eye, visual evoked field potentials were
      recorded from all successfully grafted, but not in unsuccessfully grafted (with
      the exception of one animal) nor control animals. Unitary spike responses to
      diffuse flash stimuli were recorded exclusively from three successfully grafted
      animals. Morphological reinnervation was examined in the remaining grafted (n =
      12) and control (n = 7) animals by anterogradely labeling the regenerating
      retinal axons with WGA-HRP. Axons in the grafts and their terminals in the
      superficial layers of the SC were clearly labeled in 8 of the grafted and none of
      the controls. From these results we conclude that the brachium of the SC is
      conducive to axonal regeneration and the peripheral nerve graft is indeed
      effective in restoring distally axotomized visual pathway in adult mammals.

PMID- 8566217
TI  - Murine and human mast cell express acetylcholinesterase.
AB  - Expression of catalytically active protein was detected in a murine mast cell
      line. The primary type of AChE mRNA produced by these cells was found to be the
      brain and muscle type by PCR amplification of alternative exons from the 3' of
      mast cells AChE cDNA. AChE was further found to be expressed in the HMC-1 the
      human mast cell precursor line. Furthermore, utilizing the single cell RT-PCR
      method we detected AChE mRNA expression in Fc epsilon RI-positive single cells
      derived from human colonic mucosal biopsies. Our findings predict the involvement
      of mast cell AChE in neuronal-mast cell interactions.

PMID- 8566218
TI  - Neutrophils convert tyrosyl residues in albumin to chlorotyrosine.
AB  - Hypochlorous acid chlorinates tyrosyl residues in small peptides to produce
      chlorotyrosine. Detection of chlorotyrosine has the potential to unequivocally
      identify the contribution hypochlorous acid makes to inflammation. I have
      developed a selective and sensitive HPLC assay for measuring chlorotyrosine. When
      albumin was exposed to reagent hypochlorous acid, or that produced by
      myeloperoxidase and stimulated neutrophils, tyrosyl residues in the protein were
      converted to chlorotyrosine. About 2% of the hypochlorous acid generated by
      neutrophils was accounted for by the formation of chlorotyrosine. These results
      demonstrate that chlorotyrosine will be a useful marker for establishing a role
      for hypochlorous acid in host defence and inflammation.

PMID- 8566219
TI  - Molecular cloning of a 74-kDa regulatory subunit (B" or delta) of human protein
      phosphatase 2A.
AB  - Based on amino acid sequence data of a 74-kDa regulatory subunit (B" or delta) of
      a human heterotrimeric protein phosphatase 2A, a cDNA encoding the subunit was
      isolated from a human cerebral cortex library. The cDNA had an open reading frame
      encoding an M(r) 66,138 protein of 570 amino acids. Bacterial expression of the
      cDNA yielded a protein immunoreactive with antisera specific to the 74-kDa
      subunit. The predicted primary structure of the subunit had no similarity to
      already reported sequences of PP2A regulatory subunits including A, B, and PR72.
      Potential phosphorylation sites for protein kinases A and C, a bipartite motif of
      putative nuclear localization signal, and SH3 accessible proline-rich domain, and
      a unique PQ repeat were found in the sequence. The subunit mRNA of about 2.9 kb
      was ubiquitously expressed in rat tissues.

PMID- 8566220
TI  - The TRH-like peptides in rabbit testis are different from the TRH-like peptide in
      the prostate.
AB  - Human seminal fluid contains a number of tripeptide amides with similar
      structures to thyrotropin releasing hormone (TRH), two of which have been
      identified as pGlu-Glu-Pro amide and pGlu-Phe-Pro amide. To determine whether
      these peptides originate in the same tissues and have the same molecular origin,
      TRH-immunoreactive peptides were extracted from the prostate and testis of the
      rabbit, purified by ion exchange chromatography and HPLC, and identified by co
      chromatography with 3H-labelled marker peptides. In addition, trypsin digestion
      was used to release TRH-like tripeptides from N-extended forms of these peptides.
      The sole TRH-like peptide in the prostate was shown to be pGlu-Glu-Pro amide; it
      was not accompanied by a detectable amount of pGlu-Phe-Pro amide. The prostate
      also appeared to contain a very small amount of N-extended forms of these
      peptides. In contrast to the prostate, the testis contained high concentrations
      of N-extended forms of pGlu-Phe-Pro amide but essentially no tripeptide. The
      testis also contained N-extended forms of two other neutral TRH-like peptides
      which were less hydrophobic than pGlu-Phe-Pro amide. Neither the prostate nor the
      testis contained a significant amount of TRH. The results show that in the rabbit
      the TRH-like peptides pGlu-Glu-Pro amide and pGlu-Phe-Pro amide occur in
      different tissues and appear to be formed from different precursors.

PMID- 8566221
TI  - The alpha 2/delta subunit of voltage sensitive Ca2+ channels is a single
      transmembrane extracellular protein which is involved in regulated secretion.
AB  - The membrane topology of alpha 2/delta subunit was investigated utilizing
      electrophysiological functional assay and specific anti-alpha 2 antibodies. (a)
      cRNA encoding a deleted alpha 2/delta subunit was coinjected with alpha 1C
      subunit of the L-type calcium channel into Xenopus oocytes. The truncated form,
      lacking the third putative TM domain (alpha 2/delta delta TMIII), failed to
      amplify the expressed inward currents, normally induced by alpha 1C coinjected
      with intact alpha 2/delta subunit. Western blot analysis of alpha 2/delta delta
      TMIII shows the appearance of a degraded alpha 2 protein and no expression of the
      full-size two-TM truncated-protein. The improper processing of alpha 2/delta
      delta TMIII suggests that the alpha 2/delta is a single TM domain protein and the
      TM region is positioned at the delta subunit. (b) External application of anti
      alpha 2 antibodies, prepared for an epitope within the alternatively spliced and
      'intracellular' region, inhibits depolarization induced secretion in PC12,
      further supporting an external location of the alpha 2 subunit and establishing
      delta subunit as the only membrane anchor for the extracellular alpha 2 subunit.

PMID- 8566222
TI  - Intercellular Ca2+ waves sustain coordinate insulin secretion in pig islets of
      Langerhans.
AB  - Insulin release was investigated in parallel with changes in cytosolic calcium
      concentration, [Ca2+]i, in pig islets stimulated by glucose. After two days in
      culture, glucose stimulation failed to induce insulin release, and caused limited
      [Ca2+]i changes in few cells. After ten days, insulin response was partially
      restored and [Ca2+]i recordings revealed a slow oscillatory activity of the whole
      islet. Slow oscillations appeared to be due to the average [Ca2+]i variations
      resulting from the spreading of waves throughout the islet. These waves
      demonstrate the reestablishment of functional cell coupling, which appears to
      play a critical role in insulin release.

PMID- 8566223
TI  - Resistance against cucumber mosaic virus in plants expressing the viral replicon.
AB  - CMV RNAs 1 and 2 are considered to constitute the viral replicon. Tobacco plants
      were transformed with either RNA1 or RNA2 to produce plant lines V1 and V2,
      respectively. Plants homozygous for each of the RNAs were generated and crossed
      to produce V1V2 (V2V1) lines that expressed both RNA1 and RNA2. An RNase
      protection assay indicated that RNA1 and RNA2 multiplied in V1V2 (V2V1) plants.
      Surprisingly, V1V2 (V2V1) plants, unlike their parent lines, showed a remarkably
      high level of resistance to CMV; this resistance was more effective against RNA
      inoculation than against virion inoculation. Experiments using protoplasts showed
      that the resistance was expressed at the single cell level. All the data together
      suggested that the observed resistance does not fit the criteria for either 'RNA
      mediated' or 'replicase-mediated' resistance.

PMID- 8566224
TI  - The K+ channel inward rectifier subunits form a channel similar to neuronal G
      protein-gated K+ channel.
AB  - G protein-activated inwardly rectifying K+ channel subunits GIRK1 (Kir 3.1),
      GIRK2 (Kir 3.2), and CIR (Kir 3.4) were expressed individually or in combination
      in Xenopus oocytes and CHO cells. GIRK1 coexpressed with CIR or GIRK2, produced
      currents up to 10-fold larger than any of the subunits expressed alone. No such
      clear synergistic effects were observed upon coexpression of CIR/GIRK2 under the
      same conditions. Coexpression of G protein beta gamma (G beta 1 gamma 2)
      increased the current through GIRK1/GIRK2 and GIRK2 channels. G beta gamma
      subunits purified from bovine brain, increased channel activity 50-1000-fold in
      patches from cells expressing GIRK1/GIRK2 or GIRK2 alone. The single GIRK1/GIRK2
      channels resembled previously described neuronal G protein-gated K+ channels. In
      contrast, single GIRK2 channels were short-lived and unlike any previously
      described neuronal K+ channel. We propose that some neuronal G protein-activated
      inward rectifier K+ channels may be formed by a GIRK1/GIRK2 heteromultimer and
      that G beta gamma activation may involve both subunits.

PMID- 8566225
TI  - Yeast Cls2p/Csg2p localized on the endoplasmic reticulum membrane regulates a non
      exchangeable intracellular Ca2+ pool cooperatively with calcineurin.
AB  - Saccharromyces cerevisiae CLS2 gene product (Cls2p) that is localized on the
      endoplasmic reticulum is important for the regulation of intracellular Ca2+ in a
      compartment distinct from the vacuole. Using a vma3 mutation that impairs the
      Ca2+ sequestering activity into the vacuole, we have shown that the cls2 mutation
      results in 3.4-fold increase in the Ca2+ pool that is not exchangeable with
      extracellular Ca2+. Accumulation of Ca2+ within the cls2 cells is synergistically
      elevated by the addition of immunosuppressant, FK506. Moreover, in the vma3
      background, toxicity caused by the cls2 mutation is greatly enhanced by FK506.
      Given that FK506 inhibits the calcineurin activity, Cls2p likely functions in
      releasing Ca2+ flux from the endoplasmic reticulum, somehow cooperating with
      calcineurin.

PMID- 8566226
TI  - Evidence for farnesol-mediated isoprenoid synthesis regulation in a halophilic
      archaeon, Haloferax volcanii.
AB  - Farnesol strongly inhibited growth of a halophilic archaeon, Haloferax volcanii,
      with an IC50 value of only 2 microM (0.4 microgram/ml) in rich medium and 50 nM
      (0.01 microgram/ml) in minimal medium without lysis. Other isoprenoid alcohols
      such as isopentenol, dimethylallyl alcohol, geraniol, and geranylgeraniol at 500
      microM did not affect its growth. Mevalonate, which is the precursor of all
      isoprenoid membrane lipids in archaea, led to recovery of the growth inhibition
      of H. volcanii, but acetate had no such effect. Farnesol inhibited incorporation
      of acetate, but not mevalonate, into the lipid fraction. These results suggest
      that farnesol inhibited the biosynthetic pathway from acetate (acetyl-CoA) to
      mevalonate. Farnesol is known to be derived from the important intermediate of
      isoprenoids, farnesyl diphosphate (FPP), and found in neutral lipid fraction from
      this archaeon. Moreover, the cell-free extracts from H. volcanii could
      phosphorylate farnesol with ATP to generate farnesyl monophosphate and FPP. We
      conclude that farnesol-mediated isoprenoid synthesis regulation system by
      controlling farnesol concentration is present in H. volcanii.

PMID- 8566227
TI  - 15N labeling method of peptides using a thioredoxin gene fusion expression
      system: an application to ACTH-(1-24).
AB  - For structure analysis of peptides by multinuclear NMR, stable isotope-labeled
      samples are required. A direct over-expression system by E. coli cells does not
      work for that purpose because of rapid degradation of the peptides and/or the
      mRNA in host cells. We here developed an over-expression system by means of
      thioredoxin gene fusion system. The fused protein composed of thioredoxin and the
      objective peptide was expressed in E. coli and then the peptide part was released
      by enterokinase. This system was successfully applied for the production of 15N
      labeled human adrenocorticotropic hormone fragment (ACTH-(1-24)) as needed for
      multinuclear NMR analysis.

PMID- 8566228
TI  - Hydroxyl radical formation from Cu(II)-trolox mixtures: insights into the pro
      oxidant properties of alpha-tocopherol.
AB  - Although widely recognised as the most important chain-breaking antioxidant of
      the lipid phase, alpha-tocopherol has also been reported to exert pro-oxidant
      activity, particularly during the Cu(II)-stimulated oxidation of low density
      lipoproteins (LDL). In the present communication, we demonstrate that hydroxyl
      radicals are generated following the interaction of Cu(II) with the alpha
      tocopherol model compound Trolox, involving the reduction of Cu(II) by Trolox and
      the subsequent reduction of molecular oxygen by Cu(I). We suggest, therefore,
      that the hydroxyl radical may be the species responsible for the initiation of
      fatty acid oxidation during the Cu(II)-stimulated oxidation of hydroperoxide-free
      LDL.

PMID- 8566229
TI  - Regulation of ob gene mRNA levels in cultured adipocytes.
AB  - mRNA levels of the ob gene product, leptin, were investigated by quantitative
      competitive RT-PCR in a mouse cell line (3T3-L1) which can be induced to
      differentiate into adipocytes. During conversion to fat cells, the level of
      leptin mRNA increased several-fold and in parallel to that for typical adipocyte
      markers like lipoprotein lipase, adipsin and glycerophosphate dehydrogenase.
      Leptin transcription, however, did not correlate with the size of the adipocytes
      measured as total triglycerides. On the other hand, mRNA levels for leptin in
      fully differentiated adipocytes were increased 2-3 fold by insulin. In contrast,
      free fatty acids exerted a concentration-dependent inhibition of leptin
      transcription while the corticosteroid dexamethasone and an elevation of
      intracellular cAMP displayed only marginal inhibitory effects on leptin mRNA
      levels.

PMID- 8566230
TI  - Post X-ray crystallographic studies of chymosin: the existence of two structural
      forms and the regulation of activity by the interaction with the histidine
      proline cluster of kappa-casein.
AB  - Calf chymosin molecules exist in the two alternative structural forms: the first
      one has S1 and S3 binding pockets occluded by its own Tyr77 residue (the self
      inhibited form); the second has these pockets free for a substrate binding (the
      active form). The preliminary incubation of the enzyme with a pentapeptide
      corresponding to the histidine-proline cluster of the specific substrate kappa
      casein results in a 200-fold increase of the hydrolysis rate for the enzyme 'slow
      substrate'. The result suggests that the cluster is an allosteric effector that
      promotes the conversion of the enzyme into the active form. These data provide
      the experimental ground for the explanation of chymosin specificity towards kappa
      casein.

PMID- 8566231
TI  - Cerebellar granule cells express a specific isoform of agrin that lacks the
      acetylcholine receptor aggregating activity.
AB  - Agrin is a synapse-organizing molecule that mediates nerve-induced aggregation of
      acetylcholine receptors and other postsynaptic components at the developing and
      regenerating vertebrate neuromuscular junctions. Several lines of evidence
      indicate that agrin might play a similar role in directing the organization of
      postsynaptic specifications of neuron-neuron synapse formation. Here we used
      immunological methods and polymerase chain reaction to identify the expression of
      agrin protein and alternatively spliced mRNA isoforms in the culture of rat
      granule cells. Anti-agrin polyclonal antibody labeled the cultured granule cells
      and it detected a protein of over 200 kDa in size from the lysate of the cultured
      cells. Analysis by polymerase chain reaction showed that the granule cells in
      culture expressed predominantly the B0 isoform of agrin mRNA. When granule cells
      were co-cultured with primary chick myotubes, there was no detectable effect on
      the aggregation of acetylcholine receptors on the surface of the myotubes. These
      results show that the cerebellar granule cells, similar to motor neurons in
      vitro, express and secrete agrin but it lacks the acetylcholine receptor
      aggregating activity.

PMID- 8566232
TI  - The 3D-structure of a natural inhibitor of cell adhesion molecule expression.
AB  - The three-dimensional structure of cyclopeptolide HUN-7293, a naturally-occurring
      inhibitor of cell adhesion molecule expression, has been determined from nuclear
      magnetic resonance data recorded in solution and from X-ray diffraction analysis
      of single crystals. The backbone conformation of HUN-7293 is characterized by two
      cis-peptide bonds in both the solution and crystalline state. Differences between
      the solution and crystal structure are visible for the orientation of some side
      chains and the strength of two transannular hydrogen bonds. Such structural
      information helps to provide insight into the molecular architecture of HUN-7293
      on the atomic level and opens the way for structure-based modifications of this
      novel inhibitor of cell adhesion molecule expression.

PMID- 8566233
TI  - Differential effects of endogenous and exogenous nitric oxide on the release of
      endothelin-1 from the intact perfused rat adrenal gland in situ.
AB  - Studies using an inhibitor of nitric oxide (NO) synthesis have suggested that
      endogenous NO may have a role in regulating endothelin release. We investigated
      the effect of endogenous and exogenous nitric oxide (NO) on the release of irET
      1. L-NAME stimulated, but L-arginine inhibited irET-1 release. Perfusing sodium
      nitroprusside (SNP), however, did not inhibit irET-1 secretion. CyclicGMP, the
      second messenger for NO action, was stimulated by SNP but not by L-arginine.
      These data demonstrate that endogenous NO inhibits of irET-1, in a manner which
      is independent of cGMP, and suggest that this action may contribute to the
      vasodilatory effect of NO.

PMID- 8566234
TI  - Protection against peroxynitrite-dependent tyrosine nitration and alpha 1
      antiproteinase inactivation by oxidized and reduced lipoic acid.
AB  - Peroxynitrite, formed by combination of superoxide radical with nitric oxide, is
      a reactive tissue-damaging species apparently involved in the pathology of
      several human diseases. Peroxynitrite nitrates tyrosine residues and inactivates
      alpha 1-antiproteinase. We show that both lipoic acid and dihydrolipoic acid
      efficiently protect against damage by peroxynitrite. By contrast, other
      disulphides tested did not. The biological antioxidant effects of
      lipoate/dihydrolipoate may involve scavenging of reactive nitrogen species as
      well as reactive oxygen species.

PMID- 8566235
TI  - Elevated cPLA2 levels as a mechanism by which the p70 TNF and p75 NGF receptors
      enhance apoptosis.
AB  - The 70-kDa TNF cell surface receptor (p70TNFR) and the related 75-kDa nerve
      growth factor (NGF) receptor (p75NGFR) can enhance cell death. Expression of
      p70TNFR or p75NGFR in HeLa cells resulted in enhanced TNF-induced apoptotic cell
      death with a corresponding elevation of cytosolic phospholipase A2 (cPLA2)
      levels. This response was apparent by 24 h, did not occur with NGF treatment or
      when vector or TrkA NGFR were expressed and was reversed by dexamethasone
      pretreatment. These findings reveal a novel mechanism by which the p70TNFR and
      p75NGFR achieve enhanced TNFR-mediated programmed cell death by elevating cPLA2
      levels.

PMID- 8566236
TI  - Nitric oxide synthase in chick embryo retina during development.
AB  - High levels of nitric oxide synthase were found in the early stages of developing
      chick embryo retina. The enzyme activity sharply decreased up to 13-day-old chick
      embryo retina, when the level of the last embryonic day was reached. The results
      show that nitric oxide is synthesized in chick embryo retina prior to
      synaptogenesis. The incubation of chick embryo retinas in presence of NMDA
      increased the synthesis of nitric oxide, thus, the appearance of nitric oxide
      production before the synaptogenesis in the retina as well as in the brain may be
      considered as signal for the development and shaping of neuronal and non-neuronal
      cells.

PMID- 8566237
TI  - 3D solution structure of copper and silver-substituted yeast metallothioneins.
AB  - 3D solution structural calculations for yeast silver(I)-substituted
      metallothionein (MT) and native copper(I) MT were completed using experimentally
      determined NOE and dihedral angle constraints, in conjunction with experimentally
      derived metal-to-Cys connectivities for AgMT which were assumed identical for
      CuMT. For the first 40 residues in both structures, the polypeptide backbone
      wraps around the metal cluster in two large parallel loops separated by a deep
      cleft containing the metal cluster. Minor differences between the two structures
      include differences in hydrogen bonds and the orientation of the N-terminus with
      the overall protein volume conserved to within 6.5%.

PMID- 8566239
TI  - Transacylase-like structure and its role in substrate channeling of 6
      hydroxymellein synthase, a multifunctional polyketide biosynthetic enzyme in
      carrot cell extracts.
AB  - 6-Hydroxymellein synthase, a multifunctional polyketide biosynthetic enzyme of
      carrot, lost the binding ability toward its co-substrates, acetyl- and malonyl
      CoAs, by the treatment with the blocking reagents for serine-OH. In contrast, the
      enzyme retained the binding ability even when the two SH groups at the reaction
      center (cysteine-SH of the condensation enzyme and cysteamine-SH of acyl carrier
      protein) were blocked, and one substrate bound to the SH-blocked enzyme was
      readily replaced by the other. It appeared that the cysteine-SH accepted only
      acetyl moiety while cysteamine-SH was preferentially malonylated in the presence
      of both of the substrates. These results suggest that transacylase-like domain is
      involved in the structure of 6-hydroxymellein synthase as a common primary
      binding site of its co-substrates, and acetyl and malonyl moieties are properly
      channeled from their CoA esters to cysteine-SH and acyl carrier protein-SH via
      this domain, respectively.

PMID- 8566238
TI  - Cloning, purification, and crystallization of Escherichia coli cystathionine beta
      lyase.
AB  - The metC gene coding for cystathionine beta-lyase of Escherichia coli has been
      cloned and used to construct an overproducing E. coli strain. An efficient
      purification scheme has been developed and the purified enzyme has been
      crystallized by the hanging drop vapour diffusion method using either ammonium
      sulfate or polyethyleneglycol 400 as precipitating agent. The crystals belong to
      the orthorombic space group C222. Their unit cell parameters are a = 60.9 A, b =
      154.7 A and c = 152.7 A. Consideration of the possible values of VM accounts for
      the presence of one dimer per asymmetric unit. The crystals are suitable for X
      ray analysis and a complete native date set to 1.83 A resolution has been
      collected using synchrotron radiation.

PMID- 8566240
TI  - The regulation of follicle growth: some clinical implications in reproductive
      endocrinology.
AB  - OBJECTIVE: To review the literature concerning the regulation of follicle growth,
      to describe a model for unifollicular ovulation based upon the information
      gleaned, and to discuss some clinical implications in reproductive endocrinology
      underscored by this expanding knowledge. DESIGN: Studies relating to follicular
      growth in lower animals and primates were reviewed. From the most pertinent
      articles the individual agents playing a significant role in the regulation of
      follicle growth were identified along with their mechanisms of action. A model
      for unifollicular development was proposed based upon the results of the review
      of these studies. Refinements in the management of some clinical problems in
      reproductive endocrinology were discussed based upon this model. RESULTS: From a
      review of these studies it appears that in the human and primate menstrual cycle
      one follicle is selected because it has adequate FSH receptors when plasma FSH
      levels are high. This follicle becomes dominant despite falling FSH levels
      because of increased sensitivity of the follicle to FSH brought about by
      intraovarian growth regulators. CONCLUSIONS: Improved care of patients requiring
      ovulation induction for differing indications should be possible with this more
      comprehensive knowledge of natural follicle growth.

PMID- 8566241
TI  - Reproductive medicine in a shrinking world.

PMID- 8566242
TI  - Frequency of abnormal karyotypes among abortuses from women with and without a
      history of recurrent spontaneous abortion.
AB  - OBJECTIVE: To compare the frequency of chromosomal abnormalities in products of
      conception from women with and without a history of recurrent spontaneous
      abortion. DESIGN: Retrospective analysis of prospectively collected material.
      SETTING: Private practice at the Genetics and IVF Institute, Fairfax, Virginia
      and Grupo de Reproduccion AGY Asociados, Mexico City, Mexico. PATIENTS: Women
      with (n = 94) and without (n = 130) a history of recurrent spontaneous abortion
      who had a spontaneous abortion between January 1, 1992 and November 1, 1994.
      INTERVENTION: Chromosomal analysis performed on products of conception using
      standard G-banding technique. MAIN OUTCOME MEASURE: The percentage of chromosomal
      abnormalities among products of conception from women with and without recurrent
      spontaneous abortion was compared. RESULTS: Among products of conception from
      women with recurrent spontaneous abortion, 57% (54/94) had abnormal and 43%
      (40/94) had normal chromosome analyses. Products of conception from women without
      recurrent spontaneous abortion had abnormal chromosome analyses in 57% (74/130)
      and normal results in 43% (56/130). CONCLUSIONS: No differences in frequency of
      abnormal karyotype were observed in products of conception from women with
      recurrent spontaneous abortion compared with women without recurrent spontaneous
      abortion.

PMID- 8566243
TI  - The effect of assisted hatching on pregnancy rates after frozen embryo transfer.
AB  - OBJECTIVE: To compare clinical pregnancy and implantation rates after transfer of
      frozen-thawed embryos prepared according to an assisted hatching protocol or a
      nonassisted hatching protocol. DESIGN: A historical cohort study in which a
      cohort of patients who underwent an assisted hatching protocol was matched for
      clinical parameters to an external historical cohort treated before assisted
      hatching was available. SETTING: In vitro fertilization-ET facility of a
      university-based practice. PATIENTS: Seventy-nine matched pairs. INTERVENTIONS:
      Nonassisted hatching patients: embryos were thawed, cultured in human tubal fluid
      + 0.5% bovine serum albumin until 48 hours and transferred. Assisted hatching
      patients: embryos thawed, cultured in human tubal fluid + 10% synthetic serum
      substitute until 72 hours, had assisted hatching and transferred. MAIN OUTCOME
      MEASURES: Clinical pregnancy (gestational sac) and implantation rates. RESULTS:
      Twelve (15.2%) clinical pregnancies per transfer in nonhatched group versus 24
      (30.4%) in hatched group. Nonhatched group: 284 embryos transferred; 15 (5.3%)
      implanted. Three pregnancies (25.0%) had two sacs. Hatched embryos: 269 were
      transferred; 37 (13.7%) implanted. Eleven pregnancies (45.8%) were multiple
      gestations (9 twins, 2 triplets). CONCLUSION: Clinical pregnancy and implantation
      rates were higher for group having assisted hatching protocol. It is not clear
      whether the improvement is due to the overall methodology change or to assisted
      hatching. Assisted hatching using the zona-drilling technique is not detrimental
      to frozen-thawed human embryos and may be beneficial.

PMID- 8566244
TI  - A model for the incorporation of intracytoplasmic sperm injection into a private
      practice in vitro fertilization program.
AB  - OBJECTIVE: To describe a method for the training of personnel and the
      implementation of intracytoplasmic sperm injection (ICSI) into an IVF program.
      The results of the first 75 cycles are reviewed. DESIGN: Retrospective review of
      the first 75 consecutive ICSI procedures. SETTING: Private, community-based IVF
      program. MAIN OUTCOME MEASURES: The fertilization rate, damage rate, ongoing
      pregnancy rate (PR), and implantation rate were measured. RESULTS: Nine percent
      of the injected oocytes were damaged. The fertilization rate was 60%, and the
      cleavage rate was 98%. Fifty-nine percent of the cycles resulted in an ongoing
      pregnancy, and the implantation rate per embryo was 26%. CONCLUSIONS: A high
      initial PR can be obtained with ICSI using a systematic training regimen.

PMID- 8566245
TI  - Endometrial thickness is a valid monitoring parameter in cycles of ovulation
      induction with menotropins alone.
AB  - OBJECTIVE: To evaluate the ability of an ultrasound (US)-measured periovulatory
      endometrial thickness to predict conception in hMG-stimulated cycles. DESIGN:
      Retrospective. SETTING: A university-based tertiary practice. PATIENTS: One
      hundred twelve patients undergoing 292 cycles of ovulation induction with hMG
      alone. MAIN OUTCOME MEASURES: A periovulatory transvaginal US measurement of
      endometrial thickness was obtained during cycles of ovulation induction with hMG
      alone. Clinical pregnancy was defined by fetal cardiac activity. Sensitivity and
      false-positive rates for multiple discriminatory values of endometrial thickness
      were calculated and a relative operating characteristic (ROC) curve was
      constructed to evaluate the performance of this test as a predictor of pregnancy.
      RESULTS: Thirty-eight of 292 cycles resulted in pregnancy. Conception and
      nonconception cycles showed similar demographics, diagnoses, peak E2, maximum
      number of follicles, midluteal P, and mean endometrial thickness. Ovulatory
      dysfunction was a more frequent diagnosis in the conception group. Relative
      operating characteristic analysis for endometrial thickness as a predictor of
      pregnancy yielded an area under the curve of 0.623 +/- 0.049 (mean +/- SD).
      CONCLUSION: Endometrial thickness is a valid screening test for conception
      outcome in cycles stimulated with hMG. A periovulatory endometrial thickness > or
      = 10 mm defined 91% of conception cycles. No pregnancy occurred when the
      endometrium measured < 7 mm.

PMID- 8566246
TI  - Correlation between salpingoscopic and laparoscopic staging in the assessment of
      the distal fallopian tube.
AB  - OBJECTIVE: To correlate the severity and extent of intraluminal tubal
      abnormalities assessed by transfimbrial salpingoscopy with traditional criteria
      for evaluating distal tubal disease at laparoscopy. DESIGN: Prospective 2-year
      clinical trial with long-term follow-up. SETTING: University-affiliated tertiary
      care reproductive medicine and surgery practice. PATIENTS: Fifty-five infertile
      women with suspected distal tubal disease or unexplained infertility.
      INTERVENTIONS: Transfimbrial salpingoscopy was performed at the time of
      laparoscopy and terminal neosalpingostomy when appropriate. Salpingoscopic and
      laparoscopic findings of 91 fallopian tubes were scored independently. RESULTS:
      No correlation between laparoscopic and salpingoscopic findings was noted in
      group I tubes (n = 51) categorized as having minimal disease or no pathology by
      traditional staging. In contrast, a strong correlation was noted between findings
      obtained from these two techniques in group II tubes (n = 40) diagnosed as having
      moderate-to-severe tubal disease at laparoscopy. Intrauterine pregnancy was
      achieved in 38.9% (7/18) of patients with mean salpingoscopy scores < or = to 12
      versus 3.8% (1/26) of patients with mean scores > 12. Life-table analyses of
      cumulative estimated pregnancy rates were significantly different between the
      groups. CONCLUSIONS: Fallopian tubes with minimal pathology appreciated at
      laparoscopy may have more significant intraluminal disease appreciated at
      salpingoscopy. In contrast, laparoscopic and salpingoscopic findings do correlate
      well in cases of more severe distal disease. Elevated mean salpingoscopy scores
      are associated with an extremely poor prognosis for conception.

PMID- 8566247
TI  - A comparison of time, temperature, and refreezing variables on frozen sperm
      motility recovery.
AB  - OBJECTIVE: To compare motility recovery among methods of thawing semen in serial
      freeze-thaw processes. DESIGN: A comparison of treatments. SETTING: Semen
      cryobank laboratory. PARTICIPANTS: Semen samples from an existing cryobank.
      INTERVENTIONS: Portions of each of 35 ejaculates were thawed serially in either a
      37 degrees C water bath for 10 minutes or at room temperature for 30 minutes.
      Motility was estimated, and the samples were immediately refrozen. Thaws were
      performed initially (T1), at 24 hours (T2), and at 1 week (T3). MAIN OUTCOME
      MEASURE: Percent motility. RESULTS: The initial motility of all samples averaged
      73.2%. Serial thaws at 37 degrees C yielded mean motility recoveries of 34.0%,
      21.8%, and 8.3% for T1, T2, and T3, respectively. Those at room temperature were
      22.4%, 7.9%, and 1.3%. Motilities progressively decreased from initial to final
      thaw regardless of temperature. Semen thawed at 37 degrees C had a higher
      motility recovery at all thaw times compared with samples thawed at room
      temperature. CONCLUSIONS: For sperm frozen rapidly in liquid nitrogen and for
      sperm subjected to multiple freeze-thaw processes, motility recovery is improved
      if thaw is carried out at 37 degrees C versus room temperature.

PMID- 8566248
TI  - Evidence that hormone receptors couple and activate a common signal transducer
      adenylyl cyclase in corpus luteum.
AB  - OBJECTIVES: To investigate whether membrane-bound hormone receptors in corpus
      luteum (CL) couple to one common adenylyl cyclase (AC) or whether each receptor
      is coupled to its own AC. DESIGN: Plasma membranes from rat CL were used to
      assess the coupling of hormone receptors to AC under conditions allowing full
      expression of the enzyme system. The response to hCG, prostaglandin E2 alpha
      (PGE2), and isoproterenol were analyzed. MAIN OUTCOME MEASURE: Adenylyl cyclase
      activity was monitored by the direct conversion of [infinity-32P]ATP into
      [32P]cyclic AMP. Results were expressed as pmol/min per mg membrane protein.
      RESULTS: Addition of hCG (200 mIU), PGE2 (100 microM), and isoproterenol(100
      microM) in the presence of a saturating (100 microM) concentration of guanine
      nucleotide resulted in a marked stimulation of the enzyme compared with controls,
      reaching 552 +/- 28, 537 +/- 42, and 558 +/- 32 (mean +/- SEM), respectively.
      Addition of hormones in pairs or all three together did not result in an additive
      response of the individual effects. Thus, in the presence of the three hormones
      together, AC stimulation was 582 +/- 41 (n = 5), a value that was not
      significantly different from the stimulation observed with each hormone alone.
      CONCLUSION: These data indicate that luteal membranes contain a single AC system.
      Therefore, hormone receptors couple and activate a common signal transducer AC in
      luteal membranes.

PMID- 8566249
TI  - Diagnosis of deep endometriosis by clinical examination during menstruation and
      plasma CA-125 concentration.
AB  - OBJECTIVES: To evaluate a clinical examination during menstruation and plasma CA
      125 concentrations to diagnose deep endometriosis. DESIGN: Prospective study in
      61 women scheduled for a laparoscopy, a retrospective study in 140 women with
      deep endometriosis, and a clinical validation study in 16 women with painful
      pelvic nodularities during menstruation. SETTING: University Hospital
      Gasthuisberg, a tertiary referral center. RESULTS: In the retrospective study,
      deep endometriosis was detected by routine clinical examination in only 36% of
      women. Lesions infiltrating deeper than 15 mm were detected in 50%. In the
      prospective study pelvic nodularities were detected by routine clinical
      examination in 4 women but were detected in 22 by clinical examination during
      menstruation. The latter was highly reliable to diagnose deep endometriosis,
      cystic ovarian endometriosis, and cul-de-sac obliteration. CA-125 concentrations
      were higher during menstruation and correlated with deep endometriosis and with
      deep and cystic ovarian endometriosis. Nodularities at clinical examination or
      follicular phase CA-125 concentrations > 35 U/mL are useful to decide that a
      bowel preparation should be given, achieving a sensitivity of 87% and a
      specificity of 83%. In the clinical validation study, deep endometriosis was
      found in 14 of 16 women. CONCLUSION: Clinical examination during menstruation can
      diagnose reliably deep endometriosis, cystic ovarian endometriosis, or cul-de-sac
      adhesions. This test, preferentially combined with a follicular phase CA-125
      assay, should be used to decide whether a preparation for bowel surgery should be
      given.

PMID- 8566250
TI  - Magnetic resonance imaging and serum CA-125 in evaluating patients with
      endometriomas prior to medical therapy.
AB  - OBJECTIVE: To determine whether magnetic resonance imaging (MRI) and serum levels
      of CA-125 can be used to evaluate patients with endometriomas before initiating
      medical treatment. DESIGN: Comparative study before and after medical treatment.
      SETTING: Shimane Medical University Hospital, Izumo, Japan. PATIENTS: Eleven
      consecutive patients with at least one endometrioma > 10 mm in maximal diameter
      that was diagnosed by laparoscopy and treated with 900 micrograms/d buserelin
      acetate for 6 months. INTERVENTIONS: Magnetic resonance imaging and blood
      sampling was performed < 2 weeks before laparoscopy. MAIN OUTCOME MEASURES:
      Signal intensity of edometrioma/signal intensity of gluteus maximum muscle on T2
      weighted image (T2SI:MSI); volume of endometrioma and serum CA-125. RESULTS:
      There was a positive linear correlation (r = 0.787) between T2SI:MSI before
      treatment and the extent of decrease in the volume of endometrioma. There was a
      negative linear relationship between serum CA-125 before treatment and the mean
      extent of decrease in the cyst volume (r = 0.678). The reduction in volume of
      endometrioma and T2SI:MSI before treatment related to the outcome of patients.
      CONCLUSION: The T2SI:MSI on MRI and serum CA-125 may be useful for estimating the
      outcome of patients with endometriomas before initiating medical treatment.

PMID- 8566251
TI  - Transvaginal ultrasonography combined with CA-125 plasma levels in the diagnosis
      of endometrioma.
AB  - OBJECTIVE: To assess the role of transvaginal ultrasonography combined with CA
      125 plasma levels in the diagnosis of endometrioma. DESIGN: Prospective study
      with pathological confirmation of the diagnosis. SETTING: Department of
      Obstetrics and Gynecology of the University of Cagliari, Italy. PATIENTS: One
      hundred one consecutive premenopausal nonpregnant women submitted to laparoscopy
      or laparotomy, from November 1993 to October 1994, because of the presence of an
      adnexal mass. INTERVENTIONS: Within 2 days before surgery all patients underwent
      transvaginal ultrasonography and evaluation of CA-125 plasma levels. The
      ultrasonographic impression and the CA-125 value were then compared with the
      histopathological diagnosis. MAIN OUTCOME MEASURE: The overall agreement between
      the test result and the actual outcome was calculated using the kappa index for
      the transvaginal ultrasonography used alone and for the combination of
      transvaginal ultrasonography and CA-125 values, for each chosen cutoff and range.
      RESULTS: Transvaginal ultrasonography has a strong agreement between test and
      surgery (kappa value 0.76) whereas the combined use of the two methods is
      associated with a lower kappa index, ranging from 0.40 to 0.69. CONCLUSION:
      Transvaginal ultrasonography used alone has a better predictive capacity in
      differentiating endometrioma from other adnexal masses than combined methods.

PMID- 8566252
TI  - Endometriosis and pelvic pain: relation to disease stage and localization.
AB  - OBJECTIVES: To determine whether prevalence and severity of pain symptoms are
      related to endometriosis stage and site, with particular reference to deep
      infiltrating vaginal lesions. DESIGN: Systematic assessment of chronic pelvic
      pain symptoms. SETTING: University hospital endometriosis center. PATIENTS: A
      total of 244 consecutive symptomatic patients with endometriosis diagnosed at
      laparoscopy or laparotomy. INTERVENTIONS: Assessment of dysmenorrhea and
      nonmenstrual pain by means of a 10-point linear analog scale, a 7-point
      multidimensional rating scale, and a 3-point verbal scale; evaluation of deep
      dyspareunia with the first and third systems only. MAIN OUTCOME MEASURES:
      Prevalence and severity of pain symptoms in relation to endometriosis stage and
      site of lesions. Correlation between revised American Fertility Society score and
      symptoms severity, as well as between two pain scales to assess dysmenorrhea and
      nonmenstrual pain. RESULTS: Eighty-eight women had stage I and II disease and 156
      had stage III and IV disease. Only ovarian endometriosis was present in 108
      patients, only peritoneal implants were present in 37, combined ovarian and
      peritoneal lesions were present in 57, and histologically confirmed vaginal
      endometriosis was present in 42. The frequency and severity of deep dyspareunia
      and the frequency of dysmenorrhea were less in patients with only ovarian
      endometriosis than in those with lesions at other sites. Patients with vaginal
      endometriosis had a significantly increased risk of deep dyspareunia compared
      with those whose lesions were at other sites (odds ratio, 2.55; 95% confidence
      interval, 1.21 to 5.39). Stage per se, independent of lesion site, was not
      correlated with frequency and severity of dysmenorrhea and nonmenstrual pain. The
      severity of deep dyspareunia was related inversely to the endometriosis score
      (Spearman correlation coefficients for linear analog and verbal rating scales,
      respectively, -0.22 and -0.20). Kendall test by ranks revealed a correlation
      between linear analog and multidimensional pain scales in the rating of both
      dysmenorrhea and nonmenstrual pain (respectively, tau-b, 0.59 and tau-b, 0.68).
      CONCLUSIONS: Endometriosis stage in the current classification was not related
      consistently to pain symptoms. The presence of vaginal lesions was associated
      frequently with severe deep dyspareunia. Dysmenorrhea and nonmenstrual pelvic
      pain were assessed with equal accuracy by a linear analog and a multidimensional
      scale.

PMID- 8566253
TI  - Comparison of carbon dioxide and normal saline for uterine distension in
      outpatient hysteroscopy.
AB  - OBJECTIVE: To evaluate patient acceptance and the clinical feasibility of carbon
      dioxide compared with normal saline for uterine distension in outpatient
      hysteroscopy. DESIGN: Prospective, randomized clinical trial. SETTING: Outpatient
      hysteroscopy clinic in a university hospital. PATIENTS: One hundred fifty-seven
      patients undergoing outpatient hysteroscopy. INTERVENTIONS: Outpatient
      hysteroscopy was performed with carbon dioxide or normal saline with endometrial
      biopsy when indicated. MAIN OUTCOME MEASURES: Need for local anesthesia, cervical
      dilatation, view of uterine cavity, need to change from carbon dioxide to normal
      saline distension, procedure time, patient discomfort (lower abdominal pain,
      shoulder tip pain, nausea) and complications. RESULTS: Carbon dioxide was used
      for uterine distension in 79 women and normal saline was used in 78. Cervical
      dilatation was required more often with carbon dioxide hysteroscopy, although
      there was no increased requirement for local anesthesia. Hysteroscopic vision was
      similar between the two media, but eight carbon dioxide cases had to be converted
      to liquid distension. Procedure times were significantly longer for carbon
      dioxide hysteroscopy as was the occurrence of bubbles during the procedure. Lower
      abdominal pain and shoulder tip pain were significantly worse with carbon dioxide
      distension. Although the incidence of nausea and vomiting was higher with the use
      of carbon dioxide, the differences did not achieve statistical significance.
      CONCLUSION: The use of normal saline for uterine distension had no adverse
      affects on the hysteroscopic view. It provided a shorter operating time and was
      well accepted by patients. Because of its easy availability and low cost, normal
      saline is an excellent alternative to carbon dioxide in women undergoing
      outpatient hysteroscopy.

PMID- 8566254
TI  - Hysteroscopy versus hysterectomy for the treatment of abnormal uterine bleeding:
      a comparison of cost.
AB  - OBJECTIVE: To compare the costs of hysteroscopic treatment of abnormal uterine
      bleeding with the costs associated with abdominal and vaginal hysterectomy.
      DESIGN: Retrospective review. SETTING: Academic medical center and outpatient
      gynecology practice. PATIENTS: A list of all women undergoing an endometrial
      ablation (n = 60), hysteroscopic myomectomy (n = 14), abdominal (n = 192), or
      vaginal (n = 37) hysterectomy between June 1, 1987 and June 1, 1992 for the
      treatment of abnormal uterine bleeding was generated by a computer search of
      billing records using the appropriate ICD-9-CM codes. MAIN OUTCOME MEASURE: The
      direct cost per case for each patient were defined as the sum of the surgeon's
      fee, all related hospital and operating room charges, the anesthesiologist's fee,
      and the cost of preoperative medications. When the initial procedure failed, the
      cost associated with any additional surgery was accounted for in the
      determination of the direct cost per case. Indirect costs per case were
      calculated based on known demographic data, recovery time, and the cost in lost
      productivity during recuperation. Mean direct and indirect costs per case were
      determined for each procedure and compared. RESULTS: The mean direct cost per
      case for endometrial ablation was $5,159 and for myomectomy and ablation was
      $5,525. The direct cost per case was not different between the hysteroscopic
      procedures but both were significantly less expensive than either vaginal
      ($8,132) or abdominal ($8,833) hysterectomy. Total hospital cost also was
      significantly less for the hysteroscopic procedures than for hysterectomy by
      either technique. The indirect costs associated with the hysteroscopic procedures
      were significantly less than those incurred by abdominal and vaginal
      hysterectomy. CONCLUSIONS: The total direct and indirect cost per case of an
      hysteroscopic approach to the treatment of abnormal uterine bleeding is
      significantly less than that associated with vaginal or abdominal hysterectomy.
      This difference persists when the cost of failure of an hysteroscopic procedure
      is accounted for.

PMID- 8566255
TI  - Color Doppler hysterosalpingography in the diagnosis of tubal patency.
AB  - OBJECTIVE: To assess tubal patency by color Doppler hysterosalpingography (HSG).
      DESIGN: Comparative study of color Doppler HSG with roentgenogram HSG and
      chromolaparoscopy in infertile women of childbearing age. SETTING: Clinical
      environment. PATIENTS: Sixty female patients (22 to 39 years) with long-lasting
      infertility problems. INTERVENTION: Sterile saline was transcervically injected
      into the uterine cavity through a catheter and color Doppler HSG was performed.
      All the patients were submitted to roentgenogram HSG and chromolaparoscopy. MAIN
      OUTCOME MEASURES: The diagnostic efficacy of color Doppler HSG and its
      concordance with "gold standard" chromolaparoscopy were analyzed. RESULTS:
      Correlation between color Doppler HSG and roentgenogram HSG with
      chromolaparoscopy occurred in 86% versus 93% of all women studied. CONCLUSIONS:
      Color Doppler HSG with its accuracy and safety results a promising alternative
      technique to roentgenogram HSG in diagnosing tubal status in infertile patients.

PMID- 8566256
TI  - Antiproliferative effects of low-dose micronized progesterone.
AB  - OBJECTIVE: To study the pharmacodynamic effects of oral micronized P on
      endometrial maturation. DESIGN: This was a controlled, open, parallel group,
      pilot study. SETTING: The experiment was performed in an outpatient academic
      clinical research unit. PATIENTS: Twelve healthy, P-challenged, estrogen-primed,
      postmenopausal women participated in the study. INTERVENTIONS: Patients were
      given 300 mg micronized P daily (8:00 A.M.) or twice (8:00 A.M. and 4:00 P.M.)
      daily from study days 1 through 14 after estrogen priming for 30 days. Blood
      samples were taken at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after the 8:00 A.M.
      dose on study day 1 and 14 and again at 8:00 and 9:30 A.M. on days 3 and 5
      fasting, days 7 and 9 after a fatty meal, and day 11 after a high fiber meal.
      Endometrial biopsies were taken on day 1 and 14. MAIN OUTCOME MEASURES:
      Progesterone concentrations were measured. Endometrial biopsies were studied for
      effects on histology, glycogen content of glands, ribosomal RNA, and nuclear
      estrogen receptors in glands, surface epithelium, and stroma. RESULTS: Day 1 and
      14 P kinetics were similar for 8 hours. Dose-dependent increases in glandular
      glycogen, decrease in ribosomal RNA, and decrease in nuclear estrogen receptors
      were demonstrated. CONCLUSIONS: Oral micronized P can induce antiproliferative
      changes in the human endometrium at doses lower than those required for
      transformation of the endometrium to a full secretory state.

PMID- 8566257
TI  - Comparison of transdermal versus oral estradiol on endometrial receptivity.
AB  - OBJECTIVE: To compare the effects of oral micronized E2 with transdermal E2 on
      endometrial receptivity in women undergoing oocyte donation. DESIGN: Prospective,
      randomized, crossover trial. Serum E2 and P concentrations were measured on cycle
      days 14 and 22 (luteal day +8). Endometrial biopsies were obtained on day 22 and
      read in a blinded fashion for histology and beta-3-integrin expression. SETTING:
      University-based donor oocyte program. PATIENTS: Twenty-seven patients presenting
      for donor oocytes. MAIN OUTCOME MEASURES: Endometrial histology and beta-3
      integrin expression. RESULTS: The endometrial glandular histology in women given
      oral micronized E2 was delayed by a mean of 1.6 days in comparison to that of
      women given transdermal E2. Seventy percent of women given oral E2 displayed a
      lag > or = 4 days whereas 29.6% given transdermal E2 displayed a similar lag.
      Serum E2 levels were 1,194 +/- 108.8 pg/mL (mean +/- SEM; conversion factor to SI
      unit, 3.671) in women on oral micronized E2 and 117.4 +/- 14.0 pg/mL in those on
      transdermal E2. CONCLUSION: The supraphysiologic serum E2 levels associated with
      oral micronized E2 may have a deleterious impact on endometrial receptivity. The
      development of more physiologic hormone replacement protocols may enhance
      endometrial receptivity and lead to improved clinical pregnancy rates.

PMID- 8566258
TI  - Characterization of idiopathic premature ovarian failure.
AB  - OBJECTIVE: To characterize women with idiopathic premature ovarian failure (POF)
      by their ovarian ultrasonographic appearances to establish the prevalence of
      follicular activity and relationship to autoimmunity, estrogen status, and
      historical background. DESIGN: Retrospective analysis of clinical, endocrine,
      autoimmune, ultrasonographic, and bone densitometry parameters. SETTING:
      Reproductive Endrocrinology Clinics of The Middlesex Hospital, London, United
      Kingdom. PATIENTS: Data from 135 women with idiopathic POF were analyzed. A
      reference group of 18 women with normal ovarian function, studied in their
      follicular phase, was used for comparison of endocrine and ultrasound data. A
      reference group of 57 women with normal ovarian function was used for comparison
      of bone densitometry measurements. MAIN OUTCOME MEASURES: Serum E2
      concentrations, autoantibody screen, ultrasonographic measures of ovarian volume,
      uterine cross-sectional area and endometrial thickness and dual roentgenogram
      bone mineral densitometry of the lumbar spine. RESULTS: The detection of ovaries
      by ultrasound (in 76%) and follicular activity (in 60% of patients) was
      associated with higher bone mineral density compared with women in whom ovaries
      could not be identified. Of 13 patients presenting with primary amenorrhea,
      ultrasonography identified ovaries in 62% and follicles in 38% whereas 38% had
      positive autoimmunity. Evidence of autoimmunity was found in 31% of patients
      overall and these were indistinguishable from the nonautoimmune remainder in
      every respect. CONCLUSIONS: Ovarian follicular activity, previously considered to
      be rare, as in the "resistant ovary syndrome," is found in the majority of women
      with POF using pelvic ultrasonography. Patients presenting with primary
      amenorrhea have a similar degree of ovarian function, determined by ultrasound,
      and autoimmunity as those presenting with secondary amenorrhea. The role of
      autoimmunity in the pathogenesis of POF is not distinguished from nonautoimmune
      ovarian damage by the measurements made in this study.

PMID- 8566259
TI  - The effect of add-back treatment with tibolone (Livial) on patients treated with
      the gonadotropin-releasing hormone agonist triptorelin (Decapeptyl).
AB  - OBJECTIVE: To assess whether tibolone can prevent the bone loss and symptomatic
      side effects normally associated with GnRH agonist (GnRH-a) use and whether
      tibolone modifies the effect of GnRH-a on endometriosis. DESIGN: Prospective,
      double-blind, placebo-controlled, group comparative study. SETTING: Gynecological
      research unit in a London teaching hospital. PATIENTS: Twenty-nine patients with
      endometriosis and two with fibroids. INTERVENTIONS: Six months of treatment with
      3.75 mg/mo IM triptorelin combined with daily tablets of either placebo or 2.5 mg
      tibolone. MAIN OUTCOME MEASURES: Daily symptom diary for hot flushes and bleeding
      episodes, laparoscopic scoring of endometriosis, endocrine and biochemical
      changes, and bone mineral density scans. RESULTS: Lumbar spine bone mineral
      density decreased significantly from baseline in the placebo group (-5.1%) but
      not in the tibolone group (-1.1%). The frequency of hot flushes and sweating
      episodes was reduced significantly by tibolone. There was no difference between
      the two treatment groups with regard to the endometriosis scores. CONCLUSIONS:
      The addition of tibolone to GnRH-a treatment reduces the bone loss and vasomotor
      symptoms that normally occur with GnRH-a, thus making long-term treatment with
      GnRH-a safer and more acceptable. It does not negate the therapeutic effect of
      GnRH-a on endometriosis.

PMID- 8566260
TI  - Environment of the preimplantation human embryo in vivo: metabolite analysis of
      oviduct and uterine fluids and metabolism of cumulus cells.
AB  - OBJECTIVE: To determine the levels of metabolites surrounding the human oocyte
      and embryo in vivo. DESIGN: Oviduct and uterine fluids were collected throughout
      the menstrual cycle. Cumulus cells were collected at oocyte retrieval and their
      production of metabolites was assessed. Samples were analyzed for pyruvate,
      lactate, and glucose by microfluorimetry. PATIENTS: Luminal fluids were collected
      from naturally cycling patients at the time of routine clinical investigation.
      Patient consent and hospital ethics approval were obtained for this study.
      RESULTS: Pyruvate in the oviduct did not vary with the day of cycle, the mean
      value was 0.24 mM. Lactate and glucose concentrations varied with the day of
      cycle; lactate increasing from 4.87 mM in the follicular phase to 10.50 mM at the
      time of ovulation, whereas glucose decreased from 3.11 mM in the follicular phase
      to 0.50 mM midcycle and subsequently increased to 2.32 mM in the luteal phase.
      The concentrations of pyruvate, lactate, and glucose in uterine fluid remained
      constant throughout the cycle (0.10, 5.87, and 3.15 mM, respectively). All
      metabolite concentrations in uterine fluid were significantly different from
      those in the oviduct midcycle. Cumulus cells readily consumed glucose in vitro,
      with lactate being the major metabolite produced. CONCLUSION: These data indicate
      that lactate and glucose concentrations in the oviduct change with day of cycle
      and that the human embryo is exposed to different metabolite concentrations as it
      passes along the tract. Furthermore, cumulus cells readily consume glucose,
      producing lactate. Therefore, the early human embryo is exposed to low glucose
      and high lactate levels in vivo.

PMID- 8566261
TI  - The effects of hormone replacement therapy on uterine fibroids in postmenopausal
      women.
AB  - OBJECTIVE: To evaluate and compare the effects of two different modalities of
      hormone replacement therapy (HRT) on the size of uterine fibroids. DESIGN:
      Randomized clinical study. SETTING: The Menopause Center of a public hospital.
      PATIENTS: Postmenopausal women with small asymptomatic uterine fibroids were
      selected. INTERVENTIONS: One group was treated with 50 micrograms transdermal E2
      plus 5 mg medroxyprogesterone acetate (MPA) continuously, whereas the second
      group was given 0.625 mg conjugated equine estrogen plus 2.5 mg MPA continuously.
      MAIN OUTCOME MEASURE: The size of the uterine fibroids was measured before and
      after the first year of HRT. RESULTS: At the end of the first year on HRT, the
      size of the uterine fibroids was re-evaluated sonographically and no significant
      difference was found with the oral group, whereas there was a significant
      increase in the transdermal group. CONCLUSION: Hormone replacement therapy with
      50 micrograms transdermal E2 plus 5 mg MPA increases the size of the uterine
      fibroids.

PMID- 8566262
TI  - Birth of a healthy girl after preimplantation gender determination using a
      combination of polymerase chain reaction and fluorescent in situ hybridization
      analysis. Preimplantation Genetics Group.
AB  - OBJECTIVE: To perform preimplantation gender determination by a combination of
      polymerase chain reaction (PCR) sexing and fluorescent in situ hybridization
      technique using the directly labeled fluorescent alpha-satellite centromeric DNA
      probes for X and Y chromosomes. SETTING: The IVF program of Illinois Masonic
      Medical Center. PATIENTS: A couple requested preimplantation diagnosis because
      the mother is a carrier for hemophilia A. RESULTS: Two blastomeres were aspirated
      from each of the four- to eight-cell embryos, and only the embryos with both
      fluorescent in situ hybridization and PCR results indicating female sex
      chromosomal complement were transferred, resulting in a singleton pregnancy and
      delivery of a healthy female infant, after prenatal confirmation of the diagnosis
      as female. The male embryos or embryos diagnosed as females only by PCR were
      followed up by confirmatory fluorescent in situ hybridization analysis
      demonstrating a discrepancy of PCR and fluorescent in situ hybridization results
      in four embryos, presumably because of a possible sperm contamination of the PCR
      reaction or chromosomal mosaicism. CONCLUSION: The analysis of two blastomeres
      from the same embryo by a combination of PCR sexing and fluorescent in situ
      hybridization increases the reliability of preimplantation gender identification
      at the cleavage stage.

PMID- 8566263
TI  - Assisted reproductive technologies: estimates of their contribution to multiple
      births and newborn hospital days in the United States.
AB  - OBJECTIVE: Estimate the contribution of assisted reproductive technology (ART) in
      the United States to multiple gestation births and newborn hospital days. DESIGN:
      Analysis of successful ART conceptions occurring during 1990 to 1991 compared
      with vital statistics. Newborn hospital days are estimated from the 1990 National
      Hospital Discharge Survey. SETTING: The American Fertility Society and the
      Society for Assisted Reproductive Technology registry. PATIENTS: Infants
      delivered from ART. INTERVENTIONS: Assisted reproductive technology. MAIN OUTCOME
      MEASURES: Number of multiple gestation infants and newborn hospital days.
      RESULTS: Approximately 12,327 live-born infants were delivered from ART
      conceptions during 1990 to 1991, representing 22.2% of all live-born triplet,
      17.3% of quadruplet, and 11.4% of quintuplet infants born in the United States.
      The number of newborn hospital days attributed to ART infants was 87,135 days.
      Between the periods 1972 through 1974 and 1990 through 1991, the rate of triplet
      and higher order multiple gestation infants per 100,000 white live births
      increased by 191%, with 38% due to ART conceptions and 30% to increased
      childbearing among older women. CONCLUSIONS: Assisted reproductive technology
      contributed 22% of U.S. triplet and higher order multiple births during 1990 to
      1991.

PMID- 8566264
TI  - Results of in vitro fertilization and embryo transfer in women with infertility
      due to genital tuberculosis.
AB  - OBJECTIVE: To determine the results of IVF-ET in women with infertility due to
      genital tuberculosis. DESIGN: Retrospective case-control study. SETTING: In vitro
      fertilization and ET unit of a university hospital. PATIENTS: Forty-four cycles
      of IVF-ET were undertaken in 24 women with genital tuberculosis and the results
      were compared with 366 cycles in 274 nontuberculous tubal factor couples.
      INTERVENTIONS: All women with genital tuberculosis were evaluated with
      hysteroscopy, endometrial biopsy, and acid fast bacilli stain before treatment
      with IVF-ET. RESULTS: Subjects with genital tuberculosis had higher basal FSH
      levels, required more exogenous gonadotropins for controlled ovarian
      hyperstimulation, reached lower peak E2 levels, and yielded fewer oocytes and
      embryos when compared with tubal factor patients. Furthermore, in women with
      genital tuberculosis, clinical pregnancy rate per cycle was lower and spontaneous
      abortion rate was higher. CONCLUSIONS: Women with genital tuberculosis appear to
      represent a less favorable subset within other tubal factor patients when treated
      with IVF-ET.

PMID- 8566265
TI  - Transvaginal three-dimensional ultrasound: accuracy of follicular volume
      measurements.
AB  - OBJECTIVES: To evaluate the accuracy of three-dimensional (3-D) ultrasound (US)
      follicular volume measurements. DESIGN: Prospective clinical study. SETTING: A
      tertiary referral center for assisted reproduction. PATIENTS: Twenty-five
      patients undergoing ovarian stimulation for IVF-ET using the long protocol of
      GnRH agonist. INTERVENTION: Transvaginal two-dimensional (2-D) and 3-D ovarian
      scan performed immediately before US-directed follicle aspiration. MAIN OUTCOME
      MEASURES: The volume of follicular fluid aspirated was compared with the
      corresponding volume of the follicle measured by 3-D US and with the conventional
      2-D US volume measurement calculated using the formula pi/6 (D1 x D2 x D3).
      Limits of agreement and 95% confidence intervals were calculated and systematic
      bias between the methods was analyzed. RESULTS: The limits of agreement between
      the volume of follicular aspirate and follicular volume determined by US were
      +0.96 to -0.43 mL for 3-D measurements and +3.47 to -2.42 mL for 2-D
      measurements. CONCLUSIONS: The true volume of ovarian follicles, within the
      clinically useful range for IVF-ET cycles, is measured more accurately by a 3-D
      US system than by 2-D US techniques.

PMID- 8566266
TI  - Assessment of uterine artery blood flow on the day of human chorionic
      gonadotropin administration by transvaginal color Doppler ultrasound in an in
      vitro fertilization program.
AB  - OBJECTIVE: To assess whether measurement of uterine artery blood flow impedance
      (the pulsatility index) as determined by transvaginal color Doppler ultrasound on
      the day of hCG administration in patients undergoing IVF can predict pregnancy
      and implantation rates. DESIGN: Prospective observational study of women
      undergoing IVF. SETTING: A tertiary referral center for assisted reproduction.
      PATIENTS: One hundred thirty-five patients undergoing 139 IVF cycles.
      INTERVENTION: Transvaginal color Doppler assessment of uterine artery pulsatility
      index on the day of administration of hCG. MAIN OUTCOME MEASURES: Mean
      pulsatility index of the left and right uterine arteries, pregnancy rate, and
      embryo implantation rate. RESULTS: The patients were grouped into pregnant and
      nonpregnant groups and according to whether the pulsatility index was low (1.00
      to 1.99), medium (2.00 to 2.99), or high (> or = 3.00). The pregnancy rates were
      13.8%, 34.7%, and 14.3% for the low, medium, and high pulsatility index groups,
      respectively, and were not significantly different. The implantation rates for
      the same groups were 10.7%, 16.3%, and 5.4%, respectively. The implantation rate
      for all the patients with pulsatility index < 3.00 (and especially 2.00 to 2.99)
      was significantly higher than the high pulsatility index group. CONCLUSIONS: The
      study suggests that the measurement of uterine artery pulsatility index on the
      day of hCG predicts subsequent implantation rates. It may allow the
      administration of hCG to be deferred until uterine artery pulsatility index falls
      to < 3.00, which may result in improved implantation rates.

PMID- 8566267
TI  - An improvement in the embryo quality and pregnancy rate by the pulsatile
      administration of human menopausal gonadotropin in patients with previous
      unsuccessful in vitro fertilization attempts.
AB  - OBJECTIVE: To examine whether the pulsatile administration of hMG improves IVF
      outcomes in patients with previous unsuccessful attempts using IM injections of
      hMG. DESIGN: A prospective randomized study. SETTING: In vitro fertilization
      program at a university hospital. PATIENTS: Eighty-eight endocrine-normal
      ovulatory women under 40 years of age, with normal male partners and a history of
      unsuccessful IVF treatment by the IM administration of hMG. INTERVENTIONS:
      Patients were assigned randomly to receive either IM (bolus group) or pulsatile
      administration of hMG (pulsatile group) after pituitary desensitization by a GnRH
      agonist. MAIN OUTCOME MEASURES: The proportion of retrieved oocytes with a polar
      body, the number of fertilized oocytes and embryos, the proportion of
      morphologically superior embryos, and the rate of pregnancy per initiated cycle
      were compared. RESULTS: The proportion of retrieved oocytes with a polar body and
      the number of fertilized oocytes and embryos were similar in both groups.
      Significantly more embryos had superior morphology in the pulsatile group (77%)
      than the bolus group (52%). The rates of overall and clinical pregnancy per
      initiated cycle were significantly higher in the pulsatile group (39% and 30%,
      respectively, n = 44) than in the bolus group (18% and 11%, respectively, n =
      44). CONCLUSION: In women with failed IVF attempts using IM administration of
      hMG, the pulsatile administration of hMG produces superior embryos and, hence, a
      higher pregnancy rate.

PMID- 8566268
TI  - Different gonadotropin and leuprorelin ovulation induction regimens markedly
      affect follicular fluid hormone levels and folliculogenesis.
AB  - OBJECTIVES: To clarify the endocrine mechanisms underlying the outcome of
      different ovulation induction regimens with gonadotropins and GnRH agonists (GnRH
      a). DESIGN: Prospective study. SETTING: Reproductive Endocrinology Center,
      University of Bologna. PATIENTS: Forty eumenorrheic women randomly assigned to
      four groups of 10 subjects each. INTERVENTIONS: Ovulation induction regimens:
      group A, purified FSH only; group B, purified FSH and flare-up GnRH-a; group C,
      purified FSH and long GnRH-a; and group D, hMG and long GnRH-a. MAIN OUTCOME
      MEASURES: Pelvic ultrasound and hormone levels in daily serum samples and in
      follicular fluid drawn immediately before hCG administration. RESULTS: Exogenous
      gonadotropin dose did not differ among groups. Group B had fewer preovulatory
      follicles than group C. Group B had higher serum LH, FSH, E2, P, T, and
      follicular fluid LH, E2, T, and alpha-inhibin than groups C and/or D. Groups C
      and D did not differ. CONCLUSIONS: Long GnRH-a regimens improved follicle yield
      and the endocrine milieu in spite of comparable exogenous gonadotropin dose and
      lower serum FSH and thus appear to be preferable in assisted reproduction.
      Reduced folliculogenesis found in flare-up GnRH-a regimens could be mediated by
      the atretic effects of high intraovarian androgens. Efficacy of purified FSH and
      hMG was comparable.

PMID- 8566269
TI  - Diminished alpha-inhibin messenger ribonucleic acid in in vitro fertilization
      embryo transfer poor responders reflects declining follicle reserve.
AB  - OBJECTIVES: To quantitate and compare granulosa cell alpha-inhibin messenger RNA
      (mRNA) levels in IVF-ET poor and good responders and thereby learn how alpha
      inhibin mRNA levels change in states of diminished ovarian responsiveness.
      DESIGN: Ribonucleic acid analysis of stored luteinized granulosa cell samples.
      SETTING: Academic tertiary care institution. PATIENTS: Fifty-three women
      undergoing follicle aspiration for IVF-ET were studied. Patients were classified
      as poor responders (n = 16) or good responders (n = 37) according to their E2
      concentration on the day of hCG; the E2 of poor responders was < 1,000 pg/mL
      (3,671 pmol/L) and that of good responders was > or = 1,000 pg/mL (3,671 pmol/L).
      MAIN OUTCOME MEASURES: Messenger RNA levels were measured using dot blot RNA
      analysis. The following parameters were determined or derived: total mRNA levels,
      total alpha-inhibin mRNA levels, alpha-inhibin mRNA per follicle, and
      proportional alpha-inhibin mRNA as the ratio of alpha-inhibin mRNA:total mRNA.
      RESULTS: Proportional alpha-inhibin mRNA and alpha-inhibin mRNA per follicle were
      not significantly different between poor responders and good responders. Total
      mRNA and total alpha-inhibin mRNA levels, however, were diminished significantly
      in poor responders. CONCLUSIONS: The observations that proportional alpha-inhibin
      mRNA and alpha-inhibin mRNA per follicle do not significantly change in poor
      responders, whereas total alpha-inhibin mRNA does, indicate that the decrease in
      total alpha-inhibin mRNA in poor responders reflects a decreased pool of total
      mRNA, likely because of a reduction in follicle number. These findings are in
      contrast to other recent reports that describe a change in granulosa cell
      function accompanying states of decreased ovarian responsiveness.

PMID- 8566270
TI  - The sperm stress test: a novel test that predicts pregnancy in assisted
      reproductive technologies.
AB  - OBJECTIVE: To develop a reliable sperm test that would predict pregnancy rate in
      assisted reproductive technologies. DESIGN: Blind prospective cohort study.
      SETTING: Tertiary-care, university hospital-affiliated IVF program. PATIENTS: One
      hundred nineteen sperm samples were obtained from 110 males from couples
      undergoing IVF or GIFT (ART). Sperm samples were washed by Percoll, incubated at
      24 degrees C for 4 hours, and an aliquot of the same sperm suspension was used
      for ART incubated at 40 degrees C for 4 hours (stress test). Stress test scores
      are expressed as the ratio of final to initial motility. RESULTS: Of 119 ART
      cycles, 24 resulted in pregnancy. Of 24 pregnancies, 23 occurred in cycles that
      used sperm samples with stress test scores > or = 0.75 and only one with a stress
      test score < 0.75. The negative predictive value of the test, defined as the
      absence of pregnancy with scores < 0.75, was 98% and the positive predictive
      value, defined as the occurrence of pregnancy with scores > or = 0.75, was 36%.
      Logistic regression analysis indicated that the stress test score alone was
      correlated significantly with pregnancy after ART. CONCLUSION: These results
      indicate that stress test scores < 0.75 are predictive of poor pregnancy outcome
      in ART.

PMID- 8566271
TI  - Serum hormone concentrations during treatment with multiple rising doses of
      recombinant follicle stimulating hormone (Puregon) in men with hypogonadotropic
      hypogonadism.
AB  - OBJECTIVE: To study increases of serum FSH and gonadal response in gonadotropin
      deficient men treated with recombinant FSH (Puregon; NV Organon, Oss, The
      Netherlands). DESIGN: An open, prospective, multiple rising dose study in which
      volunteers received single daily IM doses of recombinant FSH for 3 weeks. The
      dose administered was increased at weekly intervals: the first 7 days, 75 IU/d;
      the subsequent 7 days, 150 IU/d; and the last 7 days, 225 IU/d. PARTICIPANTS:
      Nine men suffering from isolated gonadotropin deficiency or panhypopituitarism.
      MAIN OUTCOME MEASUREMENTS: Immunoreactive FSH, LH, inhibin, T, and
      androstenedione. RESULTS: Serum immunoreactive FSH (median) rose in accordance
      with the recombinant FSH doses administered from 0.5 mIU/mL (range < 0.05 to 1.9
      mIU/mL) at baseline to 4.3 mIU/mL (range 2.0 to 8.5 mIU/mL), 8.4 mIU/mL (range
      4.9 to 17.8 mIU/mL), and 13.6 mIU/mL (5.6 to 28.4 mIU/mL) after 1, 2, and 3 weeks
      of medication, respectively. The elimination half-life of recombinant FSH was 48
      +/- 5 hours (mean +/- SD), which was slightly longer than that reported after
      single dose administration of recombinant FSH (32 +/- 12 hours). The bioactivity
      of recombinant FSH was reflected by serum inhibin levels, which rose from 116 U/L
      (range 34 to 356 U/L) at baseline to 350 U/L (range 63 to 1,109 U/L) at day 22.
      However, serum FSH and inhibin levels did not correlate when compared after 1, 2,
      and 3 weeks of recombinant FSH administration. Serum immunoreactive LH, T,
      androstenedione, and E2 were 0.2 mIU/mL (range < 0.05 to 0.7 mIU/mL [conversion
      factor to SI unit, 1.0]), 58 ng/dL (range < 12 to 222 ng/dL [conversion factor to
      SI unit, 0.0347]), 14 ng/dL (range 6 to 115 ng/dL [conversion factor to SI unit,
      0.0349]), and 14 pg/mL (range < 14 to 16 pg/mL [conversion factor to SI unit,
      3.67]), respectively, at baseline and remained unchanged during the entire
      treatment period. CONCLUSION: These data indicate that recombinant FSH treatment
      increases serum FSH in a dose-proportional fashion, increases inhibin secretion,
      and lacks intrinsic LH activity.

PMID- 8566272
TI  - Protective effect of antioxidants on the impairment of sperm motility by
      activated polymorphonuclear leukocytes.
AB  - OBJECTIVE: To test the ability of antioxidants to reduce the loss of sperm
      motility caused by reactive oxygen species generated by polymorphonuclear
      leukocytes (PML). DESIGN: Standardized preparations of leukocyte-contaminated
      semen were created by suspending known concentrations of purified spermatozoa and
      PML in seminal plasma. After the stimulation of reactive oxygen species
      generation with phorbol ester, the spermatozoa were washed and incubated in
      culture medium before an analysis of their movement. The ability of antioxidants
      to counteract the free radical-induced loss of sperm motility observed under
      these circumstances was assessed. SETTING: An institutional research laboratory.
      PARTICIPANTS: The semen was obtained from normal volunteers. INTERVENTIONS: The
      following were tested: vitamins C and E, dimethylsulfoxide, catalase,
      hypotaurine, N-acetylcysteine, and reduced glutathione. MAIN OUTCOME MEASURES:
      Reactive oxygen species generation was monitored by luminol-dependent
      chemiluminescence. Sperm motility was assessed manually and by computer-aided
      semen analysis. RESULTS: Consistent impairment of sperm motility and average path
      velocity was observed in the presence of activated PML. This effect was reduced
      by the concomitant presence of glutathione, N-acetylcysteine, hypotaurine, and
      catalase. CONCLUSION: Antioxidants can protect against the damaging effect of
      leukocyte-derived reactive oxygen species on sperm movement and may be of
      clinical value in assisted conception procedures.

PMID- 8566273
TI  - The effect of coculture on the postfertilization development of in vitro-matured
      monkey oocytes.
AB  - OBJECTIVE: To determine if the developmental potential of embryos resulting from
      in vivo- and in vitro-matured monkey oocytes could be increased through the use
      of a coculture system. DESIGN: Randomized prospective comparison of embryos
      resulting from either in vitro- or in vivo-matured oocytes cocultured with Vero
      cells or cultured in medium alone (control). SETTING: Basic research laboratory.
      MAIN OUTCOME MEASURES: In vitro embryo development to the blastocyst stage and
      blastocyst hatching. RESULTS: No significant difference in development was noted
      between coculture and control groups with embryos resulting from in vivo-matured
      oocytes. However, coculture was found to improve significantly the development of
      monkey embryos resulting from in vitro-matured oocytes. CONCLUSIONS: These
      results demonstrate that primate embryos resulting from in vitro-matured and in
      vitro-fertilized oocytes differ in their culture requirement when compared with
      embryos resulting from in vivo-matured oocytes.

PMID- 8566274
TI  - The role for the uterine insulin-like growth factor I in early embryonic loss
      after superovulation in the rat.
AB  - OBJECTIVES: To examine possible roles of the insulin-like growth factor (IGF)
      system in increased early embryonic loss after superovulation. DESIGN: Changes in
      the uterine IGF system were examined in superovulated rats. Insulin-like growth
      factor I (IGF-I) was infused to the right uterine horns to mimic enhanced IGF-I
      actions after superovulation. Uterine luminal fluids were collected after IGF-I
      infusions and embryos were cultured with uterine luminal fluids. MAIN OUTCOME
      MEASURES: Steroid hormones, IGF-I, IGF binding protein (IGFBP), and IGF-I
      receptor levels, developmental rate, and cell numbers of embryos. RESULTS:
      Elevated IGF-I levels and suppressed IGFBP levels were found from days 1 to 3 of
      pregnancy after superovulation. Uterine luminal fluids of the IGF-I infusion and
      superovulation groups impaired embryo development in vitro. Anti-IGF-I antibody
      infusions after superovulation reversed detrimental effects of superovulation.
      Dialysis of uterine luminal fluids of the IGF-I infusion and superovulation
      groups before culture improved embryo development. CONCLUSIONS: Enhanced IGF-I
      actions in the uterus after superovulation may be responsible for the increase of
      early embryonic loss. The detrimental factor for embryo development seems a small
      molecule and is likely a local product of the uterus in which IGF-I actions are
      enhanced.

PMID- 8566275
TI  - Pubarche induction with testosterone treatment in women with panhypopituitarism.
AB  - OBJECTIVE: To evaluate the efficacy and safety of T therapy in the induction of
      pubic hair growth in women with congenital panhypopituitarism. DESIGN:
      Prospective clinical study. SETTING: Patients followed at the University
      Endocrinology Clinic. PATIENTS: Four women with congenital panhypopituitarism,
      showing no pubic hair development, currently treated with substitutive therapy
      with L-thyroxine, cortisone acetate, and estrogen-progestin combination.
      INTERVENTIONS: A long-acting T preparation (25 to 50 mg) was given IM each month;
      serum T levels were determined before and after 12 and 24 months of therapy. MAIN
      OUTCOME MEASURE: Evaluation of pubarche stages (according to Tanner
      classification of stages). RESULTS: Patients developed pubarche (Tanner stage 3
      to 5) after 3 to 18 months of T therapy. Testosterone levels were within the
      normal range during treatment. No hirsutism or other side effects were recorded.
      CONCLUSION: A cautious T treatment represents an effective and safe approach to
      the problem of pubarche induction in women with congenital panhypopituitarism.

PMID- 8566276
TI  - Vaginal cabergoline in the treatment of hyperprolactinemic patients intolerant to
      oral dopaminergics.
AB  - OBJECTIVE: To evaluate the effectiveness and tolerance of vaginal cabergoline in
      hyperprolactinemic patients intolerant to oral dopaminergics. DESIGN: Case
      reports. SETTING: University hospital endocrinological outpatient clinic.
      PATIENTS: A 35-year-old primipara woman with idiopathic hyperprolactinemia and a
      22-year-old female with primary amenorrhea harboring macroprolactinoma.
      INTERVENTIONS: Treatment with vaginal cabergoline (0.5 mg two and five times a
      week). MAIN OUTCOME MEASURES: The serum PRL levels and side effects were assessed
      before and during treatment. RESULTS: A single vaginal dose of 0.5 mg cabergoline
      reduced serum PRL levels by approximately 50% to 85% of basal values over a
      period of 4 to 5 hours. In the patients with idiopathic hyperprolactinemia, serum
      PRL levels normalized during long-term treatment, whereas in the one with
      macroprolactinoma they remained above the normal values (79 ng/mL [conversion
      factor to SI unit, 3.180]) despite resumption of menses and marked tumor
      shrinkage (70% reduction). No side effects were reported. CONCLUSIONS: Vaginal
      cabergoline is a safe and effective method of therapy for hyperprolactinemia and
      it avoids the adverse events of oral administration.

PMID- 8566277
TI  - Evaluation of serum creatine kinase levels in ectopic pregnancy.
AB  - OBJECTIVE: To analyze whether increased serum creatine kinase (CK) levels are
      useful in early detection of ectopic pregnancy (EP). DESIGN: Prospective cohort
      study. SETTING: Patients in a university-based reproductive endocrinology and
      infertility practice. PATIENTS: Infertile women who achieved clinical pregnancy.
      INTERVENTIONS: Serum CK with isoenzymes levels were drawn after sonographic
      evaluation in patients achieving clinical pregnancy. MAIN OUTCOME MEASURES:
      Comparison of serum CK levels in patients with EP versus those with normal and
      abnormal intrauterine pregnancy (IUP), both separately and together as one group.
      RESULTS: There was no significant difference in mean total CK levels for patients
      with EP (82.25 +/- 81.39 IU/L; conversion factor to SI unit, 1.00) versus normal
      IUP (62.54 +/- 44.79 IU/L), abnormal IUP (55.15 +/- 3.46 IU/L), or all IUP (60.87
      +/- 40.72 IU/L). The mean gestational ages were similar in all three groups: EP,
      46.78 +/- 6.65 days; normal IUP, 47.56 +/- 8.29 days; and abnormal IUP, 47.86 +/-
      13.30 days. CONCLUSION: Serum CK levels do not help to predict EP for infertility
      patients achieving conception. To assist in preventing maternal morbidity, a more
      discriminative test is needed to identify this condition early in gestation.

PMID- 8566278
TI  - Manual versus computer-automated semen analyses. Part III. Comparison of old
      versus new design MicroCell Chambers.
AB  - OBJECTIVE: To determine accuracy and precision of old and new design MicroCell
      counting Chambers analyzed manually and with a computer-automated semen analyzer
      (CASA; Hamilton-Thorn Research, Beverly, MA). DESIGN: Prospective study using
      comparative measurements of the concentration of latex beads with old and new
      design MicroCell Counting Chambers (Conception Technologies, Inc. La Jolla, CA).
      MAIN OUTCOME MEASURE: Beads were counted manually and with CASA to evaluate the
      accuracy of old and new design 20 MicroCell Chambers. RESULTS: The old design 20
      MicroCell Chamber demonstrated a significant difference in bead concentration
      beginning at the 9.9 mm CASA stage position compared with stage positions of 0.0
      to 9.5 mm. The new design 20 MicroCell Chamber demonstrated the same difference
      at the 8.0 mm CASA stage position compared with stage positions 0.0 to 7.6 mm.
      Similar findings were observed when the beads were analyzed manually.
      CONCLUSIONS: When analyzed within a specific range of stage positions, the old
      and new design 20 MicroCell Chambers are accurate and precise whether analyzed
      manually or with CASA.

PMID- 8566279
TI  - Retrieval of epididymal sperm.

PMID- 8566280
TI  - Are sperm wheat germ agglutinin receptors involved in fertilization?

PMID- 8566281
TI  - Sperm decline--real or artifact?

PMID- 8566282
TI  - Progesterone, impedance to blood flow, and luteal inadequacy?

PMID- 8566283
TI  - Regulation of integrin alpha 5 beta 1 function by anti-integrin antibodies and
      divalent cations.

PMID- 8566284
TI  - Hyperglycaemia, reperfusion injury and menadione cause identical damage to the
      mitochondrial DNA of cultured vascular endothelial cells.

PMID- 8566285
TI  - Calmodulin regulation of utrophin actin binding.

PMID- 8566286
TI  - Evidence for a utrophin-glycoprotein complex in cultured cell lines and a
      possible role in cell adhesion.

PMID- 8566287
TI  - Association of structural repeats in alpha-actinin.

PMID- 8566288
TI  - Observation of ATP turnover during in vitro motility assays.

PMID- 8566289
TI  - Caged FEDA-ATP: a new tool in the measurement of ATP turnover during the in vitro
      motility assay.

PMID- 8566290
TI  - Damage to the vascular endothelium of diabetic patients can be assessed by
      analysing blood samples for the number of circulating endothelial cells with
      mitochondrial DNA deletions.

PMID- 8566291
TI  - Mechanisms of melanoma cell adhesion to fibronectin.

PMID- 8566292
TI  - A collagen peptide motif activates calcium signalling in SaOS-2 cells.

PMID- 8566293
TI  - Fatty acylation of polypeptides in the free-living nematode Caenorhabditis
      elegans.

PMID- 8566294
TI  - G(o1) alpha palmitoylation: its contribution to alpha 2C10 adrenoceptor--G(o1)
      alpha coupling.

PMID- 8566295
TI  - Characterisation of the fatty acid delta 12-desaturase of Acanthamoeba
      castellanii.

PMID- 8566296
TI  - Inhibition of dietary cholesterol ester absorption by 3-BCP, a suicide inhibitor
      of cholesterol-esterase.

PMID- 8566297
TI  - Influence of plasma membrane fluidity on phagocytotic activity in Acanthamoeba
      castellanii.

PMID- 8566298
TI  - Anion permeability of the basolateral membrane from the ovine parotid acinar
      cells.

PMID- 8566299
TI  - Dimethylsulphoxide stabilizes gel phases of phosphatidylcholines.

PMID- 8566300
TI  - Stabilization of the non-lamellar phase of dioleoylphosphatidylethanolamine by
      dimethylsulphoxide.

PMID- 8566301
TI  - The role of intracellular proteolysis in the regulation of apolipoprotein B
      secretion by rabbit hepatocytes.

PMID- 8566302
TI  - Candidate proteins involved in the targeting of the insulin-sensitive glucose
      transporter GLUT4 in adipocytes.

PMID- 8566303
TI  - Sequence analysis and molecular dynamics studies of potassium channel
      transmembrane helices.

PMID- 8566304
TI  - Effects of halothane on mu opioid binding in SH-SY5Y cells.

PMID- 8566305
TI  - Ketamine inhibits K+ evoked [3H] noradrenaline release from SH-SY5Y cells by
      reducing calcium influx.

PMID- 8566306
TI  - Do SH-SY5Y human neuroblastoma cells express cannabinoid receptors?

PMID- 8566307
TI  - Mu-opioid activation of phospholipase C in SH-SY5Y cells rapidly desensitizes:
      mechanistic studies.

PMID- 8566308
TI  - 2-Hydroxyethyl alpha-D-glucopyranoside 2,3',4'-trisphosphate: a novel
      metabolically resistant adenophostin A and myo-inositol 1,4,5-trisphosphate
      analogue potently interacts with the myo-inositol 1,4,5-trisphosphate receptor.

PMID- 8566309
TI  - Effect of lithium on muscarinic cholinoceptor-stimulated phosphoinositide
      specific phospholipase C substrate selectivity in CHO-m1 cells.

PMID- 8566310
TI  - Developmental expression of FK506 binding proteins and calcineurin in rat brain.

PMID- 8566311
TI  - Developmental changes in glutathione levels in neonatal rat brain.

PMID- 8566312
TI  - Regulation of bradykinin responses by PKC epsilon and histamine responses by PKC
      alpha in adrenal chromaffin cells.

PMID- 8566313
TI  - Stimulation of nitric oxide synthase by endothelial purinoceptors does not
      correlate with inositol trisphosphate levels.

PMID- 8566314
TI  - Tyrosine phosphorylation, MAPK and PLD in AII stimulated mitogenesis.

PMID- 8566315
TI  - Activation of phospholipase D in SH-SY5Y neuroblastoma cells: dependence on Ca2+
      and protein kinase C.

PMID- 8566316
TI  - Modulation of the inositol 1,4,5-trisphosphate-sensitive calcium channel from rat
      cerebellum by alkali metal ions.

PMID- 8566317
TI  - The effects of cholesterol hemisuccinate and other membrane fluidity perturbing
      agents on inositol 1,4,5-trisphosphate-induced calcium release from cerebellar
      microsomes.

PMID- 8566318
TI  - Phenol isolation of DNA yields higher levels of 8-oxodeoxyguanosine compared to
      pronase E isolation.

PMID- 8566319
TI  - Development of an assay to measure 8-oxoguanine using HPLC with electrochemical
      detection.

PMID- 8566320
TI  - Application of capillary electrophoresis to the in vitro assessment of drug
      metabolism.

PMID- 8566321
TI  - Micellar electrokinetic capillary chromatography of 8-oxoguanine and other bases
      of DNA.

PMID- 8566322
TI  - Detection of purine lesions in cellular DNA using single cell gel electrophoresis
      with Fpg protein.

PMID- 8566323
TI  - Estimation of the dissociation constant of the cell adhesion molecules srCD2 and
      srCD48 using analytical ultracentrifugation.

PMID- 8566324
TI  - Glucose-6-phosphatase expression during rat development.

PMID- 8566325
TI  - Hormonal regulation of differentiation-related gene expression in fetal
      hepatocyte primary cultures.

PMID- 8566326
TI  - Steroid hormone induced effects on membrane fluidity.

PMID- 8566327
TI  - Integrins: dynamic regulation of ligand binding.

PMID- 8566328
TI  - Peroxidase activation of 4-hydroxytamoxifen to cause DNA damage in vitro.

PMID- 8566329
TI  - Transforming growth factor-beta isoform autocrine production by cultured ras
      transfected and tumour-derived human keratinocytes.

PMID- 8566330
TI  - Distribution of cGMP-gated cation channel expression in bovine and porcine
      cardiovascular tissue.

PMID- 8566331
TI  - RepD/D*: a protein-DNA adduct arising during plasmid replication.

PMID- 8566332
TI  - Expression of rat biliverdin reductase as a glutathione-S-transferase fusion
      protein.

PMID- 8566333
TI  - Polyamines can regulate vitamin B12 dependent methionine synthase activity.

PMID- 8566334
TI  - Stimulation of atrial natriuretic factor promoter activity by Src and Ras in
      cultured neonatal rat ventricular myocytes.

PMID- 8566335
TI  - Altered adhesions in ras-transformed breast epithelial cells.

PMID- 8566336
TI  - Changes in PKC subspecies protein expression as C6 cells reach G(0) by contact
      inhibition in the presence of serum.

PMID- 8566337
TI  - A role for protein kinase C in the multidrug resistance phenotype of human
      carcinoma KB cell lines.

PMID- 8566338
TI  - Prostaglandins increase HDL binding to human cells in culture.

PMID- 8566339
TI  - Ca(2+)-dependent and Ca(2+)-independent protein kinase C activity in human breast
      biopsies.

PMID- 8566340
TI  - The relationship between protein kinase C subspecies and multidrug resistance in
      vincristine resistant Chinese hamster ovary cells.

PMID- 8566341
TI  - The role of actin filament barbed-end exposure in cytoskeletal dynamics and cell
      motility.

PMID- 8566342
TI  - Subcellular targeting of recombinant and mammalian C alpha subunits of cAMP
      dependent protein kinase.

PMID- 8566344
TI  - Protein kinase C isoform expression and ATP response change with smooth muscle
      cell differentiation.

PMID- 8566343
TI  - Expression of PK-A catalytic and regulatory subunits in lactating rat mammary
      tissue: effects of litter removal.

PMID- 8566345
TI  - Differential calpastatin expression in cardiac and skeletal muscle.

PMID- 8566346
TI  - Investigation of the Ca(2+)-dependency of nitric oxide synthase induced in rat
      colonic mucosa by intravenous lipopolysaccharide.

PMID- 8566347
TI  - Rho, rac and cdc42 GTPases: regulators of actin structures, cell adhesion and
      motility.

PMID- 8566348
TI  - Expression of c-fos and c-myc in satellite cell cultures from dystrophic mdx and
      control mouse muscle.

PMID- 8566349
TI  - Difference spectra for inhibitor binding to monoamine oxidases.

PMID- 8566350
TI  - Angiotensin II receptors are exclusively of the AT1 subtype in cultured human
      vascular smooth muscle cells.

PMID- 8566351
TI  - Calcium signalling in human colonic epithelial cells via tyrosine kinase and G
      protein linked receptors.

PMID- 8566352
TI  - Adhesion and direct integrin engagement differentially regulate gene
      transcription, transcript stabilization and translation.

PMID- 8566353
TI  - The chronic treatment of amlodipine in regressing hypertrophy.

PMID- 8566354
TI  - Chronic effects of alcohol upon protein profiling in ventricular tissue.

PMID- 8566355
TI  - Enteral nutrition, diarrhoea and jejunal protein synthesis in vivo.

PMID- 8566356
TI  - Antioxidant status in the jejunum: effect of acute ethanol dosage.

PMID- 8566357
TI  - Signalling in extracellular-matrix-mediated control of epithelial cell phenotype.
AB  - Interactions with an appropriate ECM are crucial for normal cell behaviour. The
      basement membrane contributes to both the tissue-specific lactational function
      and survival of mammary epithelial cells, possibly through a similar beta 1
      integrin-dependent mechanism. Of current interest is whether the downstream
      intracellular signals diverge, with milk expression regulated through cell shape
      and the Jak-Stat pathway and survival mediated through controls on the Bcl-2/Bax
      and Ice checkpoints.

PMID- 8566358
TI  - Protein catabolism in metabolic acidosis: inhibition of glycolysis by low pH
      suggests a role for glucose.

PMID- 8566359
TI  - Compartmentation of total RNA in catabolism: a comparative analysis of skin,
      bone, skeletal muscle and liver in response to endotoxin and alcohol.

PMID- 8566360
TI  - The effect of supplementation on alpha-tocopherol levels in liver, heart and
      skeletal muscle.

PMID- 8566361
TI  - Time-course changes in skeletal muscle protein synthesis in vivo in response to
      ethanol.

PMID- 8566362
TI  - Characterisation of caesium transport in the microalga Chlorella salina.

PMID- 8566363
TI  - Axonal growth mediated by cell adhesion molecules requires activation of
      fibroblast growth factor receptors.

PMID- 8566364
TI  - How does the kidney deal with plasma polyamines?

PMID- 8566365
TI  - Zonula occludens (ZO)-1 and ZO-2: membrane-associated guanylate kinase homologues
      (MAGuKs) of the tight junction.

PMID- 8566367
TI  - The potential importance of MHC mimicry by HIV in the pathogenesis of AIDS.

PMID- 8566366
TI  - Renal metabolism of homocysteine in vivo.

PMID- 8566368
TI  - Predicted 3D-structure of macrophage-specific Fc gamma RI.

PMID- 8566369
TI  - Recognition of 5-HT transporter by antipeptide antibodies.

PMID- 8566370
TI  - Immunodetection of UV-induced DNA damage in a neuronal cell line.

PMID- 8566371
TI  - Signal transduction at the blood-brain barrier.

PMID- 8566372
TI  - Relationship between levels of IgG and IgM and IgM rhematoid factor in human
      sera.

PMID- 8566373
TI  - Structural studies on FMN domain of cytochrome P450 reductase.

PMID- 8566374
TI  - Probing protein structure with proteases: studies of an equilibrium intermediate
      in protein unfolding.

PMID- 8566375
TI  - Structural characterisation of a slowly activating potassium channel (IsK).

PMID- 8566376
TI  - Structure analysis of a recombinant voltage-gated potassium channel (Kv1.1) N
      terminus using FTIR spectroscopy and thermal denaturation.

PMID- 8566377
TI  - Autoantibodies to DNA in schizophrenia.

PMID- 8566379
TI  - Cell cycle and dose-dependence of DNA damage and p53 expression following UVA
      irradiation.

PMID- 8566378
TI  - Malonyl-CoA and carnitine palmitoyltransferase I: an expanding partnership.

PMID- 8566381
TI  - T cell epitopes of bovine respiratory syncytial virus attachment glycoprotein.

PMID- 8566380
TI  - Immunochemical detection of reactive oxygen species DNA damage.

PMID- 8566382
TI  - "How much biochemistry should a good doctor know?". Experiences from two new
      medical schools.

PMID- 8566383
TI  - Modification of mouse liver glutathione S-transferase Pi by iodoacetic acid.

PMID- 8566384
TI  - Regulation of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene
      expression in liver and intestine from the rat.

PMID- 8566385
TI  - Lipolysis in rat adipose tissue in vitro is dependent on the quantity and not the
      quality of dietary fat.

PMID- 8566386
TI  - Plasma mono-, di- and triacylglycerol measurements in a study of fat uptake by
      human adipose tissue in vivo.

PMID- 8566387
TI  - Characterisation of glucose-6-phosphatase activity in cultured cell lines.

PMID- 8566388
TI  - Ketogenic flux from lipids and leucine, assessment in 3-hydroxy-3-methylglutaryl
      CoA lyase deficiency.

PMID- 8566389
TI  - Microsomal carnitine acyltransferases.

PMID- 8566390
TI  - The active site histidine of carnitine acyltransferases.

PMID- 8566391
TI  - The use of spherical reconstituted high density lipoprotein for the measurement
      of cholesteryl ester transfer protein activity in human plasma.

PMID- 8566392
TI  - Marked hyperlipidaemia in rats bearing the Yoshida AH-130 ascites hepatoma.

PMID- 8566393
TI  - The effect of fasting and insulin treatment on carnitine palmitoyl transferase I
      and mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A synthase mRNA levels in
      liver from suckling rats.

PMID- 8566394
TI  - Ultra-rapid detection of mRNAs on northern blots with digoxigenin-labelled
      oligonucleotides and 'CDP-Star', a new chemiluminescence substrate.

PMID- 8566395
TI  - The enzymology of hepatic very-low-density lipoprotein assembly.

PMID- 8566396
TI  - Dietary regulation of hepatic and cardiac pyruvate dehydrogenase during the
      suckling-weaning transition in rats.

PMID- 8566397
TI  - Short-term inhibition of fatty acid and cholesterol biosynthesis by the lipid
      lowering drug gemfibrozil in primary rat hepatocyte cultures and rat liver in
      vivo.

PMID- 8566398
TI  - Mitochondrial beta-oxidation in human alcoholic liver disease.

PMID- 8566399
TI  - Predicting the phase diagram for a gelatin-pectin system.

PMID- 8566400
TI  - Notable increase in content of cytochrome P-450 enzymes in Saccharomyces
      cerevisiae in repetitive alternating culturing.

PMID- 8566401
TI  - Hormonal and nutritional control of liver fatty acid oxidation and ketogenesis
      during development.

PMID- 8566402
TI  - Autophosphorylation of cAMP-dependent protein kinase catalytic subunit.

PMID- 8566403
TI  - Insulin and the partitioning of hepatic fatty acid metabolism.

PMID- 8566404
TI  - Aspects of metabolism in normal and gestational diabetic pregnancy.

PMID- 8566405
TI  - Physiological signals and pathological mediators of lipid metabolism during
      lactation.

PMID- 8566406
TI  - The phospholipid composition of enveloped viruses depends on the intracellular
      membrane through which they bud.

PMID- 8566407
TI  - A comparison of the transmembrane domains of Golgi and plasma membrane proteins.

PMID- 8566408
TI  - Vesicle transport during cell growth and in the maintenance of cell polarity.

PMID- 8566409
TI  - The role of microtubules in apical and basolateral endocytosis in epithelial
      Madin-Darby canine kidney (MDCK) cells.

PMID- 8566411
TI  - Recycling of the endoplasmic reticulum/Golgi intermediate compartment protein
      ERGIC-53 in the secretory pathway.

PMID- 8566410
TI  - Keeping Golgi membranes intact in the pericentriolar region of mammalian cells.

PMID- 8566412
TI  - Roles for microtubules and kinesin in membrane traffic between the endoplasmic
      reticulum and the Golgi complex.

PMID- 8566413
TI  - Characterization and cellular localization of human myristoyl-COA: protein N
      myristoyltransferase.

PMID- 8566414
TI  - Viral lipoproteins: the role of myristoylation.

PMID- 8566415
TI  - The role of myristoylation in the interactions between human immunodeficiency
      virus type I Nef and cellular proteins.

PMID- 8566416
TI  - Demyristoylation of myristoylated alanine-rich C kinase substrate.

PMID- 8566417
TI  - Acylation of viral glycoproteins: structural requirements for palmitoylation of
      transmembrane proteins.

PMID- 8566418
TI  - Dynamic protein acylation and the regulation of localization and function of
      signal-transducing proteins.

PMID- 8566419
TI  - Protein palmitoylation in membrane trafficking.

PMID- 8566420
TI  - Dynamic regulation of G-protein coupled receptor palmitoylation: potential role
      in receptor function.

PMID- 8566421
TI  - G-protein palmitoylation: regulation and functional significance.

PMID- 8566422
TI  - The MARCKS family of protein kinase-C substrates.

PMID- 8566423
TI  - Subcellular targeting of kinases and phosphatases by association with
      bifunctional anchoring proteins.

PMID- 8566424
TI  - Interaction of protein kinase C with RACK1, a receptor for activated C-kinase: a
      role in beta protein kinase C mediated signal transduction.

PMID- 8566425
TI  - Intracellular targeting of protein kinase C isoenzymes: functional implications.

PMID- 8566426
TI  - 14-3-3 proteins: biological function and domain structure.

PMID- 8566427
TI  - Perilipin: unique proteins associated with intracellular neutral lipid droplets
      in adipocytes and steroidogenic cells.
AB  - For several reasons it seems reasonable to suspect that perilipins participate in
      lipid hydrolysis. First, they are located at the lipid droplet surface, the
      presumed site of HSL and cholesteryl esterase action. Secondly, they are
      polyphosphorylated by PKA in concert with lipid hydrolysis. Finally, these
      proteins appear to be expressed primarily, if not solely, in adipocytes and
      steroidogenic cells, cells in which lipid hydrolysis is stimulated by cyclic AMP
      and mediated by HSL or cholesteryl esterase(s), whereas other cells that contain
      abundant neutral lipid depositions contain no perilipin [13]. Interestingly,
      these closely related hydrolases share no homology with other mammalian lipases
      [3]. Although such attributes provide a link between perilipin and lipid
      hydrolysis, we have no evidence that perilipins participate directly in, or are
      necessary for, lipid catabolism. The basis for the strong affinity between the
      perilipins and neutral lipids is unknown. Clearly, lipids and perilipins are
      tightly linked, as evidenced by selective targeting of epitope-tagged perilipin
      to lipid droplets and by the paradoxical appearance of lipid droplets in pre
      adipocytes transfected with a sense perilipin A construct. Indeed, in
      differentiating adipocytes the earliest lipid depositions are associated with
      perilipins, and restriction of perilipin synthesis with anti-sense constructs may
      impede lipid formation and deposition. It remains to be determined if, in the
      normal course of events, perilipins are directed toward lipid depositions or if
      lipids are transported to perilipin foci. Whatever the temporal sequence, the
      result is that neutral lipids are encased in perilipin-bounded droplets.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8566428
TI  - Pleckstrin homology domains.

PMID- 8566429
TI  - Cell-matrix adhesion: structure and regulation.

PMID- 8566430
TI  - Using fluorescence to probe calcium signalling mechanisms.

PMID- 8566431
TI  - Regulation of calcium homoeostasis in neurons: the role of calcium-binding
      proteins.

PMID- 8566432
TI  - Pharmacology of sodium and calcium channel modulation in neurons: implications
      for neuroprotection.

PMID- 8566433
TI  - Why do hormones stimulate Ca2+ mobilization?

PMID- 8566434
TI  - Spatial organization of oscillating calcium signals in liver.

PMID- 8566435
TI  - Intracellular free Ca2+ responses in electrically stimulated cerebellar granule
      cells.

PMID- 8566436
TI  - Calcium transients in voltage-clamped dendrites of hippocampal neurons evoked by
      different patterns of synaptic activity.

PMID- 8566437
TI  - Endogenous pathway of class II presentation.
AB  - Assembly, targeting and peptide loading of MHC class II molecules is controlled
      by a series of mechanisms and molecular interactions that inhibit the binding of
      peptides or proteins in the ER or secretory compartment. As a consequence, the
      major site of peptide binding to class II molecules is in the endosomal/lysosomal
      compartment. The barrier, however, between exogenous and endogenous antigen
      presentation by MHC class II molecules does not seem to be as tight as for MHC
      class I, and several different mechanisms may contribute to MHC class II
      presentation of endogenous antigens. Although limited, the possibility of
      presentation of endogenous antigens may nevertheless be important in viral
      infections and in tumours, for the recruitment of CD4-positive helper T-cells.
      This may also apply when unfolded or misfolded proteins accumulate in the ER and
      compete with the invariant chain for binding to MHC class II molecules. The
      potential relevance of this pathway to triggering autoimmune reactions has yet to
      be explored.

PMID- 8566438
TI  - Modulation of immune responses to allergens of house dust mite.

PMID- 8566440
TI  - Presentation of N-formylated peptides by H2-M3.

PMID- 8566439
TI  - Antigen processing by the class I pathway.

PMID- 8566441
TI  - Predicting major histocompatibility complex-binding sequences within protein
      antigens.

PMID- 8566442
TI  - Elucidation of T-cell epitopes: a synthetic approach with random peptide
      libraries.

PMID- 8566443
TI  - Human tumour antigens recognized by T-cells: perspectives for new cancer
      vaccines.

PMID- 8566444
TI  - Processing of myelin basic protein by macrophages generates an epitope with
      apparent low affinity for I-As.

PMID- 8566445
TI  - Cellular immunity against DNA tumour viruses: possibilities for peptide-based
      vaccines and immune escape.

PMID- 8566446
TI  - Managing equinus in a child with cerebral palsy: merits of hinged ankle-foot
      orthoses.
AB  - A comparison of hinged versus solid ankle orthoses in a child with moderate
      spastic diplegia demonstrated that solid ankle braces blocked needed foot and
      ankle mobility. The loss of movement forced the child to use extraneous movement
      patterns in order to move the upper body over the foot. These iatrogenically
      induced deviations were considered reasons for surgery. When ankle and foot
      mobility were increased by the use of hinged ankle braces, the gait improved and
      with physical therapy the reasons for surgery were removed. This case study shows
      that significant biomechanical changes can be achieved by simply switching from
      solid to articulated or hinged ankle-foot orthoses.

PMID- 8566447
TI  - Acute infantile thalamic necrosis.
AB  - An acute encephalopathy of infancy presenting as seizures and coma following a
      presumably infectious disease with the distinctive finding of thalamic necrosis
      was recently described. The authors report a similar case in an 11-month-old
      infant, and discuss its possible pathogenesis.

PMID- 8566448
TI  - Growth hormone deficiency in two children with cerebral palsy.
AB  - The authors describe two children with cerebral palsy and linear growth failure
      secondary to growth hormone deficiency. One of the children was successfully
      treated with growth hormone replacement therapy. His linear growth velocity
      increased from 3cm/year before therapy to 8.3 cm/year during the first two years
      of therapy. Potential complications such as worsening orthopedic status did not
      occur. Psychosocial benefits were noted. The authors conclude that growth hormone
      deficiency may play a role in linear growth failure in some children with
      cerebral palsy and that some of these children may benefit from growth hormone
      therapy.

PMID- 8566449
TI  - Periventricular haemosiderin deposition in patients with congenital hemiplegia.
AB  - Two patients with congenital hemiplegia without obvious prenatal, perinatal or
      neonatal difficulties showed linear low signal intensity lesions along the wall
      of the dilated lateral ventricles without any parenchymal lesions on T2- and
      proton density weighted MRI. Haemosiderin deposition secondary to intra-uterine
      subependymal haemorrhage with intraventricular haemorrhage was considered most
      likely from the signal intensity, distribution and clinical histories. MRI, which
      is the only means of detecting haemosiderin deposition, could be beneficial for
      evaluating the pathogenetic cause of congenital hemiplegia.

PMID- 8566450
TI  - Prognosis for ambulation in cerebral palsy.

PMID- 8566451
TI  - Childhood multiple sclerosis--the long view from Scotland.

PMID- 8566452
TI  - Origin of brain abnormalities in bilateral spastic cerebral palsy.

PMID- 8566453
TI  - The life expectancy of persons with cerebral palsy.

PMID- 8566454
TI  - Predicting outcome and planning management.

PMID- 8566455
TI  - Outcome and prognosis of whiplash shaken infant syndrome; late consequences after
      a symptom-free interval.
AB  - Long-term follow-up five to 13 (mean seven years) of 13 cases of whiplash-shaken
      infant syndrome (WSIS) demonstrated long sign-free intervals. Full clinical
      appearance of neurological deficits takes four months for the interruption of
      brain growth, six to 12 months for lesions of the central nervous system long
      pathways, up to two years for epilepsy, and three to six years for behavioural
      and neuropsychological signs. In our series, WSIS occurred at a mean postnatal
      age of 5.5 months and caused intracranial, retinal and preretinal haemorrhages,
      intracranial haematomas, oedema, contusional tears, and developmental
      disturbances interfering with the growth and differentiation of neural tissue and
      with synaptic stabilisation. These mechanisms account for the long sign-free
      interval that makes its impossible to formulate a precise and final neurological
      prognosis before the age of school entrance. Only one of our patients seems to
      have remained normal even several years after the shaking.

PMID- 8566456
TI  - Ambulation with parapodia and reciprocating gait orthoses in pediatric spinal
      cord injury.
AB  - The use of parapodia and reciprocating gait orthoses (RGOs) was reviewed in 41
      children and adolescents with spinal cord injuries. Compared with users of RGOs,
      users of parapodia were younger when injured and when the orthotic was first
      used, were more likely to be household ambulators and to have higher neurological
      levels, and were unlikely to continue their use of the parapodium after early
      school age. Hip contractures that required surgical releases or contributed to
      discontinuation of orthotic usage were present in six of 26 parapodium users and
      12 of 22 RGO users. RGOs and parapodia have a limited but important role in
      management of pediatric spinal cord injury, and should be used in a
      developmentally based program responsive to the changing needs of children and
      adolescents.

PMID- 8566457
TI  - Managing equinus in children with cerebral palsy: electrical stimulation to
      strengthen the triceps surae muscle.
AB  - A new therapeutic proposal for the management of equinus in children with
      cerebral palsy is to strengthen the calf muscles instead of weakening them
      surgically. Prior research indicates that in children with cerebral palsy the
      triceps surae muscle is weak and needs strengthening. Neuromuscular electrical
      stimulation (NMES) was used as an adjunct to physical therapy. A portable NMES
      unit with a hand-held remote switch stimulated an active muscle gait cycle.
      Results are discussed for four children, who showed improved gait, balance,
      posture, active and passive ankle range of motion, and foot alignment. The toe
      walkers became plantigrade and the equinovalgus posture of the foot decreased.
      Spasticity did not increase.

PMID- 8566458
TI  - Kinaesthetic sensitivity and motor performance of children with developmental co
      ordination disorder.
AB  - Earlier research has demonstrated a number of variables contributing to motor co
      ordination problems (clumsiness) in children. The present study examined the
      contribution of kinaesthetic sensitivity in determining level of motor co
      ordination in children. 20 children with significant movement problems were
      compared with 20 control children matched for age, gender and Verbal IQ. The
      kinaesthetic perception and memory test from Laszlo and Bairstow's Kinaesthetic
      Sensitivity test was a powerful measure for distinguishing clumsy from control
      children. The authors' passive kinaesthetic acuity test did not distinguish the
      two groups, but did so when administered actively. These results indicate that
      future research on clumsiness in children should involve more complex tasks, as
      problems associated with the central translation processes may cause the co
      ordination difficulties seen in clumsy children.

PMID- 8566459
TI  - Development of the upright postural sway of children.
AB  - From 1988 to 1992, 1188 children (576 boys and 612 girls) three to 11 years old
      were studied using the Stasio-analyzer to clarify developmental change of upright
      postural sway. Developmental change in the contact surface area of the sole, the
      coefficient of variation for the contact surface area, total sway area, total
      sway path and position of the centre of gravity were analysed. The contact
      surface area increased markedly between the ages of three to five and of seven to
      nine years, and increased slightly between six and seven years. Age six to seven
      years is proposed as a turning point of plantar arch formation as regards change
      in the contact surface area of the sole. Upright postural sway decreased markedly
      between the ages of three to five years and then slowly after age six. Boys under
      ten years swayed more than girls. The centre of gravity of the foot in children
      standing upright shifted towards the toes with increasing age: its distance from
      the heel was about 36 per cent of the foot length at age three to five years and
      42 per cent at 11 years.

PMID- 8566460
TI  - The prediction of long-term functional outcomes of children with cerebral palsy.
AB  - Current information was obtained from 117 respondents, including 71 who completed
      interviews, of a population of 810 individuals who had been diagnosed with
      cerebral palsy between 1951 and 1974. Original chart reviews constituted the
      basis for predicting employment capabilities of the interviewed cohort. A
      comparison of predictions with actual functional outcomes demonstrated a tendency
      to pessimistic underestimation of long-term functional outcome, sounding a note
      of caution to paediatric developmentalists.

PMID- 8566461
TI  - The needs of children.

PMID- 8566462
TI  - School attainment, cognitive ability and motor function in a total Scottish very
      low-birthweight population at eight years: a controlled study.
AB  - The prevalence of learning problems and of cognitive and motor impairment in a
      total geographically based very-low-birthweight population (N = 324) was compared
      at eight years of age with that in a population comprising two classroom peers,
      matched for gender and age (N = 590). 15 per cent of those with birthweights less
      than 1000g and 6 per cent of those weighing 1000 to 1499 g attended special
      schools. Index children in main-stream schools performed significantly less well
      in tests of neuromotor function than their comparison groups. Their mean IQs were
      90.4 and 93.7 for those below and above 1000 g, respectively, while their
      comparison groups' IQs were 102.5 and 101.2. In all cognitive subscales apart
      from that testing short-term auditory sequential memory, both index groups were
      less competent. They were also less able in Word Reading and Basic Number Skills.
      These children placed heavy demands on mainstream schools, with 52 per cent and
      37 per cent of the index groups, respectively, requiring learning support
      compared with 16 per cent in both comparison groups.

PMID- 8566463
TI  - Social and biological risk factors for mild and borderline impairment of language
      comprehension in a cohort of five-year-old children.
AB  - Biological risk factors during intra-uterine life, delivery and the neonatal
      period, and measures of social adversity during pregnancy, were studied as
      predictors of a 'mildly impaired' (50 to 74) or 'borderline' (75 to 84) score on
      the Peabody Picture Vocabulary Test (PPVT) at aged five years in 3906 children.
      Biological risk factors in pregnancy were associated with neither PPVT outcome.
      Gestation of < 36 weeks, > 3 minutes to establishment of respiration and
      admission to intensive care were associated with a lower PPVT score indicating
      mild impairment, though only in the unadjusted analyses. A five minute Apgar
      score of < 5 and male sex were related to borderline scores, though only the
      latter remained significant after statistical allowance for possible confounding.
      In contrast, almost all measures of social adversity were related to both PPVT
      outcomes even after statistical adjustment for the influence of other factors.

PMID- 8566464
TI  - Correlates of physicians' decisions to refer children with cerebral palsy for
      physical therapy.
AB  - Videotapes of ten children with 'suspected' cerebral palsy were used as stimuli
      to elicit physicians' decisions regarding referral for physical therapy.
      Respondents were 99 developmental or general pediatricians, orthopaedists,
      neurologists or physiatrists who were members of the American Academy of
      Pediatrics or the American Academy of Cerebral Palsy. They rated their belief in
      the value of therapy; described their experience, training and practices relating
      to management of cerebral palsy; and responded to cases with their assessment of
      severity, diagnosis and referral decision. The decision to refer was
      significantly related to perceived severity of the condition, diagnostic
      certainty, and belief in the efficacy of physical therapy. Referral rates did not
      vary with tendency to use physical therapy for other types of patients, nor with
      training, experience or self-rated expertise in cerebral palsy.

PMID- 8566465
TI  - Medical and functional status of adults with cerebral palsy.
AB  - One hundred and one adults (19 to 74 years of age) with cerebral palsy were
      interviewed and examined. There were 52 subjects with dyskinesia, 28 with spastic
      quadriparesis, 11 with spastic diplegia, and 10 with spastic hemiplegia.
      Neuromuscular dysfunction was mild in two cases, moderate in 72 and severe in 27.
      76 per cent of the subjects had multiple musculoskeletal problems. In 63 per
      cent, these occurred under 50 years of age, suggesting that abnormal
      biomechanical forces and immobility had led to excessive physical stress and
      strain, overuse syndromes, and possibly early joint degeneration. A number of the
      patients had urinary complaints due to difficulties with toilet accessibility and
      possible neurogenic bladder. General health care seemed satisfactory for acute
      illnesses, but preventive health care was almost totally lacking. Treatment for
      the musuculoskeletal system and availability of adaptive devices were less
      adequate than for children with cerebral palsy.

PMID- 8566466
TI  - Estimating bone change in patients with severe disability.
AB  - To evaluate bone change in severely disabled patients, bone density was assessed
      on X-ray pictures by the microdensitometry (MD) method, and urinary
      hydroxyproline (U-HYP), urinary glycosaminoglycans (U-GAG) serum calcium (S-Ca)
      and serum alkaline phosphatase (S-AP) were assessed in 43 patients (mean age 16
      years) at the National Sanatrium Ehime Hospital. On division of the severity of
      bone change into grades 0 to 3 using the MD method. U-HYP was found to be
      significantly higher in grades 2 and 3 than in controls. Tendencies were similar
      for U-GAG and S-AP. U-HYP in immobile patients was significantly higher than in
      mobile patients. Immobilisation was one of the most important contributors to the
      development of bone change and results obtained using the MD method, U-HYP and U
      GAG were valuable-indices of the bone change in severely disabled patients.

PMID- 8566467
TI  - Paroxysmal phenomena in the first two years of life.
AB  - The prevalence of paroxysmal phenomena in the first two years of life was
      assessed in 1854 children of Dutch-speaking mothers of a population-based birth
      cohort. At each visit to the Child Health Clinic (CHC), mothers were asked
      whether they had noted sudden change of consciousness, involuntary movements,
      deviation of the eyes or apnoea, and if so, whether these appeared to be related
      to feeding. Paroxysmal episodes occurred in a quarter of the children: in 8 per
      cent only in relation to feeding, in 19 per cent also not related to feeding. The
      latter children were more frequently admitted to hospital and had more
      disabilities at age two years. No connection with epilepsy in the family or with
      congenital anomalies could be demonstrated. Special attention should be paid by
      the CHC team to children with paroxysmal phenomena not associated with feeding.

PMID- 8566468
TI  - Parental exposure to hydrocarbons in Prader-Willi syndrome.
AB  - The purpose of this study was to ascertain whether parental age and parental pre
      conceptional exposure to various agents differentiated children with Prader-Willi
      syndrome (PWS) from obese children without PWS. Two groups of patients under 25
      years of age were studied, 15 persons with PWS, and 13 with PWS-like symptoms. In
      the PWS group deletions were detected on chromosome 15q11-q13 and parents were
      older. The parents' occupational and recreational exposure to environmental
      toxins was recorded and correlated to the clinical diagnosis, genetics and
      behaviour characteristics. Paternal exposure to gasoline/petrol was significantly
      higher in the PWS group and is suggested as a possible important factor in the
      aetiology of PWS.

PMID- 8566469
TI  - Immunoglobulin therapy in Guillain-Barre syndrome in children.
AB  - Four children with evolving Guillain-Barre syndrome were treated with a five-day
      course of intravenous immunoglobulin. No patient showed further progression of
      the condition and all made a rapid and complete recovery with no evidence of
      relapse over a six- to 24-month follow-up period. The early use of immunoglobulin
      in this disorder may prevent further progression of the disease and accelerate
      short-term recovery, with resulting medical, social and financial implications.

PMID- 8566470
TI  - Life expectancy in cerebral palsy.

PMID- 8566471
TI  - The abuse of children with disabilities in mainstream schooling.

PMID- 8566472
TI  - Subacute measles encephalitis in a boy with perinatal HIV-1 infection.

PMID- 8566473
TI  - Pharmacokinetics of 2-ethyl-1,3-hexanediol. III. In vitro skin penetration
      comparisons using the excised skin of humans, rats, and rabbits.
AB  - Excised skin from Fischer 344 rats, New Zealand White rabbits, and human females
      (obtained from mammoplasty patients) were compared for their in vitro skin
      penetration potential with 2-[14C]-ethyl-1,3-hexanediol (EHD). EHD was applied as
      both an undiluted dose and a 3% v/v aqueous dose using a flowthrough skin
      penetration chamber design and was analyzed over 0-6 hr. The undiluted dose was
      equivalent to a 150 mg/kg dose used in vivo with rats (Frantz et al., Drug Metab.
      Dispos. 20(1), 6-18, 1992), but normalized on a per cm2 surface area basis, and
      applied under occluded conditions (covered as for in vivo studies). Undiluted
      applications of EHD did not substantially penetrate skin, with effluent
      recoveries of approximately 0.9% of the applied dose for human skin, 2-4% for rat
      skin, and 3-6% for rabbit skin. By comparison, nonoccluded human skin showed
      lower effluent radioactivity (0.6%), which was attributed to EHD evaporation from
      skin. With undiluted EHD, approximately 97% of the recovered 14C was an
      unabsorbed dose for human skin, with 94% for rat skin and 85% for rabbit skin
      (expressed as a percentage of the recovered dose). Based on HPLC analysis of
      effluent samples, 99-100% of the undiluted [14C]EHD penetrated rat, rabbit, and
      human skin in the unmetabolized form. In contrast, approximately 5% of the
      applied aqueous dose was recovered in the effluents for human skin, while 6-9%
      appeared in effluents for rat skin; rabbit skin was not evaluated for aqueous
      doses. The fraction of unabsorbed aqueous EHD dose totaled 53% of the applied
      dose for human skin and 63% for rat skin. Evaporative loss of undiluted [14C]EHD
      was also measured (captured on activated charcoal) in separate experiments and
      compared with a known standard chemical, N,N[14C]diethyl-m-toluamide (DEET).
      Evaporation of EHD was clearly a competing factor with penetration, particularly
      for human skin preparations, and evaporative losses were similar to those seen in
      previous studies. Penetration of skin was also greater for both EHD and DEET when
      evaporation was not permitted (stopped chamber). Permeability constant (kp)
      values were calculated using the pseudo steady-state slopes from plots for
      cumulative mg/cm2 penetration vs time. For undiluted EHD, human skin had the
      slowest penetration rate, while rabbit skin kp values were the largest. The kp
      values for water solutions of EHD on rat and human skin demonstrated a slightly
      higher penetration, with values of the same order of magnitude as that observed
      for a concurrently run [14C]ethanol control. The minimal skin penetration
      observed in vitro in this study, taken together with in vivo percutaneous
      pharmacokinetic studies (Frantz et al., 1992) and the known percutaneous
      toxicology of EHD, suggests that penetration through human skin and systemic
      adverse effects should be minimal.

PMID- 8566474
TI  - Assessment of offspring development and behavior following gestational exposure
      to inhaled methanol in the rat.
AB  - The prospect of widespread human exposure associated with its use as an
      alternative fuel has sparked concern about the toxic potential of inhaled
      methanol (MeOH). Previous studies have revealed congenital malformations in rats
      following inhaled MeOH (Nelson et al. (1985). Fundam. Appl. Toxicol. 5, 727-736)
      but these studies did not include postnatal behavioral assessment. In the present
      study, pregnant Long-Evans rats were placed in exposure chambers containing
      15,000 ppm MeOH or air for 7 hr/day on Gestational Days (GD) 7-19. The total
      alveolar dose of methanol was estimated at about 6.1 g/kg/day, for a total dose
      of about 42.7 g/kg for the entire study. Maternal body weights were recorded
      daily and blood methanol concentrations were determined at the end of exposure on
      GD 7, 10, 14, and 18. Following birth (Postnatal Day 0 [PND 0]), a number of
      tests were performed at various points in development, including: offspring
      mortality and body wt (PND 1,3), motor activity (PND 13-21, 30, 60), olfactory
      learning (PND 18), behavioral thermoregulation (PND 20-21), T-maze learning (PND
      23-24), acoustic startle response (PND 24, 60), reflex modification audiometry
      (PND 60), pubertal landmarks (PND 31-56), passive avoidance (PND 72), and visual
      evoked potentials (PND 160). Maternal blood MeOH levels, measured from samples
      taken within 15 min after removal from the exposure chamber, declined from about
      3.8 mg/ml on the first day of exposure to 3.1 mg/ml on the 12th day of exposure.
      MeOH transiently reduced maternal body wt (4-7%) on GD 8-10, and offspring BW
      (5%) on PND 1. No other test revealed significant effects of MeOH. Prenatal
      exposure to high levels of inhaled MeOH appears to have little effect on this
      broad battery of tests beyond PND 1 in the rat.

PMID- 8566475
TI  - Deuterium isotope effect on the metabolism of the flame retardant tris(2,3
      dibromopropyl) phosphate in the isolated perfused rat liver.
AB  - The metabolism of tris(2,3-dibromopropyl) phosphate (Tris-BP) was compared with
      that of completely deuterated Tris-BP (D15-Tris-BP) in an isolated, recirculating
      rat liver perfusion system in order to determine the relative quantitative
      importance of two different biotransformation pathways of Tris-BP: (i) cytochrome
      P450-mediated metabolism and (ii) GSH S-transferase-mediated metabolism. To
      accomplish this we quantitated the biliary excretion of S-(3
      hydroxypropyl)glutathione (GSOH) as a marker metabolite for cytochrome P450
      mediated metabolism and that of S-(2,3-dihydroxypropyl) glutathione (GSOHOH) as a
      marker metabolite for GSH S-transferase-mediated metabolism. Complete deuterium
      substitution of Tris-BP significantly decreased the formation of GSOH, whereas
      there was no effect on the formation of GSOHOH. Because our previous studies
      showed a large decrease in genotoxicity of D15-Tris-BP compared to Tris-BP, the
      present results support our hypothesis that cytochrome P450-mediated metabolism
      is responsible for the genotoxic effects of Tris-BP in the rat liver.

PMID- 8566476
TI  - The CAT-Tox (L) assay: a sensitive and specific measure of stress-induced
      transcription in transformed human liver cells.
AB  - Identifying and measuring the molecular mechanisms of toxicity is an important
      goal in hazard assessment. We have developed an assay in transformed human liver
      cells to simultaneously measure the transcriptional responses of 14 stress
      promoter- or response element-chloramphenicol acetyl transferase (CAT) fusion
      constructs that are stably integrated into the HepG2 cell line. This assay can
      measure a wide spectrum of stresses, both toxic and nontoxic, such as protein and
      protein biosynthesis perturbations, DNA damage, heavy metals, and planar aromatic
      hydrocarbons. We found that each promoter or response element can be induced by
      one or more of four chemicals that were tested in the assay. These results have
      been interpreted in light of the current models of action for each compound. The
      responses of this assay system can distinguish among compounds that are closely
      related in their structure and have been shown previously to elicit similar
      biological activities in simple assay systems. We have designated this technique
      the CAT-Tox (L)iver assay. It measures a broad range of cellular stresses and
      toxicants at levels that were comparable to or below those of established
      methods. The induction profiles generated using the CAT-Tox (L) assay can help to
      elucidate the molecular mechanisms by which chemicals exert their actions on
      human cells. These profiles can be indicative of both toxic and nontoxic
      processes that are occurring in the cell. We propose that this cellular stress
      assay can serve as a screen for a variety of substances at the molecular level.

PMID- 8566477
TI  - Subchronic toxicity studies with the leukotriene D4 antagonist RG 12525.
AB  - Preclinical safety studies with the leukotriene D4 antagonist RG 12525 were
      conducted by the oral route in mice, rats, and monkeys. Oral administration of RG
      12525 was repeated daily in studies up to 6 months in duration. RG 12525 was
      shown to have limited high-dose toxicity after repeated oral administration. The
      effects of RG 12525 were strongly dependent upon the species considered. High
      doses of RG 12525 caused significant increases in liver weight in mice, rats, and
      monkeys that were associated with diffuse hepatocellular hypertrophy in mice and
      rats but not in monkeys. No related clinical chemistry changes were observed in
      any of the species and hepatic activities of peroxisomal enzymes or cytochrome
      P450 were increased only slightly. Proliferation of brown adipose tissue (BAT)
      was observed in rats and mice but not in monkeys. The BAT reaction was more
      pronounced in the interscapular area but it was also observed in other
      subcutaneous locations as well as in mediastinal and bone marrow fat. In all
      locations, the RG 12525-induced BAT had some morphological similarities with cold
      adapted BAT. Repeated administration of RG 12525 at high doses to female rats
      resulted in a lack of progression to the luteal phase of the estrous cycle that
      was reversible after discontinuation of treatment. Finally, RG 12525 was
      nephrotoxic in mice with males being more sensitive than females.

PMID- 8566478
TI  - Development and intralaboratory evaluation of an in vitro human cell-based test
      to aid ocular irritancy assessments.
AB  - A human cell-based in vitro method was developed to screen for ocular irritancy
      potential of aqueous compatible and incompatible test agents, such as liquids,
      insoluble solids, powders, granulars, emulsions, and acids/alkalis. Methods were
      developed for topical application (an exposure that mimics in vivo testing) and
      wash-off of test substances on the epithelial surface of human skin derived
      epithelial-fibroblast cocultures (Skin2 Model ZK1200 from Advanced Tissue
      Sciences). These cultures contain noncornified stratified squamous epithelium,
      providing a three-dimensional in vitro model that resembles noncornified mucosal
      epithelium, such as cornea and conjunctiva. The hypothesis tested and confirmed
      in this work was that the rate of cytotoxicity induced by topical application of
      test substances to the stratified epithelial cell cultures would correlate with
      ocular irritancy. Test substances were applied to the cell system for up to 30
      min, and cytotoxicity was measured as decreased 3-[4,5-dimethylthiazol-2-yl]2,5
      diphenyltetrazolium bromide (MTT) vital dye metabolism. The time (in minutes) of
      exposure to test agent that reduced MTT metabolism to 50% of control levels (the
      t50 value) was calculated for each test substance, and these values showed a good
      correlation (r = 0.87) with historic rabbit low-volume eye test maximum average
      scores (MAS) for a range of liquid, solid, granular, powder, and other test
      materials, including consumer product formulations and ingredient chemicals.
      Additionally, t50 values confirmed the mild nature of selected cosmetic
      formulations. Taken together, these data indicate that this in vitro test, termed
      the tissue equivalent assay, is a valuable tool to screen for irritancy of test
      substances to mucosal tissues, such as cornea and conjunctiva.

PMID- 8566479
TI  - Developmental toxicity of 1,2-dichloropropane (PDC) in rats and rabbits following
      oral gavage.
AB  - 1,2-Dichloropropane (PDC) was evaluated for its potential to cause
      embryonal/fetal toxicity and teratogenicity in pregnant rats and rabbits. PDC was
      administered via oral gavage at dose levels of 0, 10, 30, or 125 mg/kg/day on
      Days 6 through 15 of gestation (rats) or 0, 15, 50, or 150 mg/kg/day on gestation
      Days 7 through 19 (rabbits). Fetuses were examined on Gestation Day 20 (rats) or
      Day 28 (rabbits). Maternal toxicity was observed in both rats and rabbits at the
      high dose levels. Rats given 125 mg/kg/day of PDC showed clinical signs of
      toxicity and decreased body weight and body weight gain. Rabbits given 150
      mg/kg/day PDC showed changes in hematologic parameters and decreased body weight
      gain. Although maternal toxicity was apparent, no indication of teratogenicity
      was observed in rat or rabbit fetuses at any dose level. Significant increases in
      the incidence of delayed ossification of skull bones, considered secondary to
      decreased maternal body weight gain, were observed in rats given 125 mg/kg/day
      and in rabbits given 150 mg/kg/day. No maternal or developmental effects were
      observed in rats given 10 or 30 mg/kg/day or in rabbits given 15 or 50 mg/kg/day
      of PDC. Based on the results of these studies the maternal and developmental
      NOELs in rats and rabbits were 30 and 50 mg/kg/day, respectively.

PMID- 8566480
TI  - Investigation of the prenatal toxicity of orally administered diethylene glycol
      in rabbits.
AB  - Diethylene glycol was tested for prenatal toxicity after oral administration
      (gavage) to pregnant Himalayan rabbits. The substance was administered to 15
      female rabbits per group by stomach tube in daily doses of 100, 400, or 1000
      mg/kg body wt from Day 7 postinsemination (p.i.) through Day 19 p.i. The control
      group received the vehicle only (twice distilled water). There were no compound
      related effects on the dams concerning food consumption, body weight, body weight
      gain, or clinical or necropsy observations even at the highest dose of 1000 mg/kg
      body wt/day. All data obtained on gestational parameters also revealed no
      biologically relevant differences between the control and treated groups. The
      fetal external, soft tissue, and skeletal findings, which were classified as
      malformations, variations, and/or retardations, were seen in the treated fetuses
      at a frequency similar to the corresponding and/or historical controls. Thus,
      under the conditions of this study, no signs of maternal toxicity or embryo
      /fetotoxicity were induced by diethylene glycol. Therefore, a no-observable
      adverse-effect level for diethylene glycol of > 1000 mg/kg body wt/day was
      established for both the maternal and the developing Himalayan rabbit.

PMID- 8566482
TI  - A multiple-path model of particle deposition in the rat lung.
AB  - A multiple-path model of particle deposition in the entire rat lower respiratory
      tract was developed. Deposition in every branch of an asymmetric lung model was
      calculated using published analytic formulas for efficiencies of deposition by
      sedimentation, diffusion, and impaction. The conducting airway tree of the model
      included the entire set of airway measurements for the Long-Evans rat collected
      by Raabe et al. (1976). A model acinus defined by Yeh et al. (1979) was attached
      to each terminal bronchiole. Deposition was calculated for each acinus.
      Substantial variations in acinar deposition were predicted. These depended on
      inhaled particle size and tidal volume. The standard deviation in acinar dose was
      on the order of 0.2 times the average dose. Dose to some pulmonary acini was
      nearly twice the average acinar dose, suggesting that the geometry of the
      conducting airway tree of the rat lung may cause a fraction of pulmonary sites to
      sustain damage from inhaled particles at levels of exposure which cause no effect
      in the majority of the lung. The results represent a first step toward a complete
      model of inhaled particle deposition which assesses the effect of heterogeneity
      of lung structure on deposition at the level of individual airways.

PMID- 8566481
TI  - Developmental toxicity study of clarified slurry oil (CSO) in the rat.
AB  - Pregnant CD rats were exposed dermally to 0.05, 1, 10, 50, and 250 mg/kg/day of
      Clarified Slurry Oil (CSO) on Days 0-19 of gestation to determine its potential
      developmental toxicity. Untreated and vehicle controls were included in the
      study. Day 20 of gestation Caesarean-derived fetuses were examined for gross,
      external, and visceral or skeletal alterations. Dosages of 1 mg/kg/day and higher
      significantly decreased maternal body weight, body weight gain, feed consumption,
      gravid uterine weight, and live litter size and significantly increased
      resorption rate. These dosages also significantly reduced fetal weights and
      retarded development of the brain, kidney, thoracic and caudal vertebrae,
      metacarpals, and hindpaw phalanges in dosage groups with live fetuses (high
      dosage group dams resorbed all conceptuses). The 50- and 250-mg/kg/day dosage
      group dams had only placentas and/or dark red viscous fluid in the uterus or
      vagina and significant body weight loss (associated with resorption). The highest
      dosage also caused emaciation, slight dehydration, and swollen dark anogenital
      areas. These results indicate that CSO produces adverse developmental effects at
      maternally toxic dosages. The maternal and developmental NOAELs (no observed
      adverse effect levels) were 0.05 mg/kg/day. In a second study, groups of 10 mated
      female rats were exposed to "pulse" exposures and dosages of 1, 50, or 250
      mg/kg/day of CSO applied dermally for 2- or 3-day intervals that spanned the
      gestation period. All dosages reduced maternal feed consumption and body weight
      gain during the treatment period. Dosages of 50 and 250 mg/kg/day also produced
      early resorptions when administered on Days 6 through 8 and 9 through 11 of
      gestation. However, no increase in fetal alterations occurred, indicating that
      the effects on embryo-fetal development were due to early death and not to the
      death of malformed conceptuses.

PMID- 8566483
TI  - Subacute toxicity of a purine nucleoside phosphorylase inhibitor in rats.
AB  - Rats received daily oral doses of 15, 50, 150, or 200 mg/kg CI-1000 for 4 weeks.
      Doses were selected based on findings from a 2-week range-finding study where
      doses of 250 and 500 mg/kg resulted in mortality. In the 4-week study, females
      given 200 mg/kg were sacrificed during Week 2 due to poor condition. Serum
      creatinine and urea nitrogen increased 2- to 2.5-fold in females given 200 mg/kg.
      Dose-related increases in urine volume, urinary protein excretion, and osmolar
      excretion occurred in both sexes beginning at 50 mg/kg. Kidney weights increased
      9-40% in both sexes at > or = 50 mg/kg; histopathologic changes were confined to
      the 150 and 200 mg/kg groups. At Week 4, T-suppressor/cytotoxic lymphocytes were
      reduced 43% and T-helper/inducer lymphocytes were reduced 22% in males given 200
      mg/kg. In females, T-suppressor/cytotoxic lymphocytes were significantly
      decreased (approximately 40%) at 50 and 150 mg/kg, with no significant effects on
      T-helper/inducer lymphocyte populations. At Week 8, following 4 weeks without
      treatment, T-lymphocyte subpopulations were similar in control and drug-treated
      groups. B-lymphocyte counts and percentages were increased at Weeks 4 and 8 in
      males receiving 150 or 200 mg/kg. Thymic weights decreased at Week 4 at doses of
      150 and 200 mg/kg. Plasma CI-1000 levels were higher in females than in males at
      all doses except 15 mg/kg; Cmax and AUC values were largely dose proportional in
      both sexes. In summary, CI-1000 was well-tolerated at doses of 15, 50, and 150
      mg/kg with no adverse effects occurring at 15 mg/kg. Drug-induced changes in the
      kidney were mild and reversible. Immunomodulatory effects were noted at doses of
      50 mg/kg or higher.

PMID- 8566484
TI  - Quinolone-induced arthropathy in the neonatal mouse. Morphological analysis of
      articular lesions produced by pipemidic acid and ciprofloxacin.
AB  - Quinolone antibiotics are extensively utilized in antimicrobial chemotherapy.
      However, quinolone treatment in developing adolescents of several animal species
      is associated with acute arthropathy of the weight-bearing joints. Although
      arthropathy has rarely been observed following quinolone therapy in man, the
      toxicity observed in immature animals has resulted in restricted use of these
      drugs in children and pregnant women. Therefore, identification of novel
      quinolone antibiotics which do not cause arthropathy is highly desirable. This
      task would be facilitated by a bioassay of cartilage toxicity which utilizes
      small quantities of test material and has greater sensitivity than current
      toxicity assays. This study evaluated the utility of neonatal mice as a potential
      bioassay of quinolone-induced joint toxicity. Seven-day-old CF-1 mice (8-10/dose
      group) were treated subcutaneously with either pipemidic acid (50, 400, or 3150
      mg/kg/day) for 7 or 14 days or ciprofloxacin (50 or 200 mg/kg/day) for 5, 7, or
      14 days. Lameness was observed only after high-dose pipemidic acid treatment for
      2-7 days. Histopathological assessment of the principal weight-bearing joints
      (knee, elbow, and multiple articulations in the fore- and hind-feet) revealed a
      lesion characterized by chondrocyte loss, matrix degeneration, and erosion of the
      articular cartilage in mice treated with pipemidic acid at 400 or 3150 mg/kg/day
      for 7 days or ciprofloxacin at 200 mg/kg/day for 5 days. Mice treated for 14 days
      with 400 mg/kg/day pipemidic acid demonstrated a lower incidence of lesions than
      mice treated for 7 days, suggesting the potential for reversibility during
      ongoing treatment. The results suggest that neonatal mice are sensitive to
      quinolone-induced arthropathy, but less so than previously reported for
      adolescent dogs. It is concluded that the neonatal mouse may be an appropriate
      screening system for identifying novel quinolones devoid of cartilage toxicity;
      however, follow-up studies with select compounds in a more sensitive species,
      such as the dog, are encouraged.

PMID- 8566485
TI  - Effects of gadolinium chloride on the rat lung following intratracheal
      instillation.
AB  - The metabolic behavior, clearance, and pulmonary effects of gadolinium (Gd), one
      of the rare earth elements, were investigated after single intratracheal
      instillation of gadolinium chloride (GdCl3) in male Wistar rats. There was a dose
      related increase in Gd content of lung tissue. Gd content in the supernatant of
      bronchoalveolar lavage fluid (BALF) did not exceed 5 micrograms Gd/BALF even at a
      dose of 100 micrograms Gd/rat. Gd in the lung tissue decreased very slowly with a
      biological half-life of 136 days at a dose of 50 micrograms Gd/rat. On the other
      hand, Gd content in the supernatant of BALF was not detectable after 31 days.
      These results suggest that intratracheally instilled Gd can be retained in
      epithelial lining fluid only to a limited extent as soluble forms and is
      deposited in the lung tissue probably in insoluble forms which are metabolized
      very slowly. Calcium (Ca) content in BALF increased more rapidly than other
      toxicological indices such as lactate dehydrogenase activity, protein
      concentration, and inflammatory cell counts. In the lung tissue, levels of Ca in
      Gd-instilled groups did not differ from the control value. Although these data
      suggest that the origin of Ca may be blood plasma, biological and/or
      toxicological significance of increased Ca is not known. The number of
      neutrophils reached the maximum at 12 hr after instillation, indicating that Gd
      has the potency to cause acute lung toxicity. Summarizing the observation, Gd
      instilled intratracheally into rats was deposited in the lung tissue in
      nonsoluble forms with an extremely long half-life, while the metal caused a rapid
      and selective infiltration of serum Ca before acute lung toxicity.

PMID- 8566486
TI  - Species-dependent induction of peroxisome proliferation by haloxyfop, an
      aryloxyphenoxy herbicide.
AB  - The potential of haloxyfop [2-(4-((3-chloro-5-(trifluoromethyl)-2-
      pyridinyl)oxy)phenoxy)propanoic acid; HAL] to induce the proliferation of
      hepatocellular peroxisomes (PP) was examined in rats, mice, dogs, and monkeys.
      Chemically induced PP is associated with the development of liver tumors in
      rodents via an apparent species-dependent, nongenotoxic mechanism of action. HAL
      is nongenotoxic yet has been shown to cause liver tumors in female B6C3F1 mice.
      Ingestion of HAL by rats and/or mice (0.1-14 mg/kg/day for 2 to 4 weeks) resulted
      in significant dose-related PP as evidenced by hepatocellular hypertrophy,
      increased peroxisome volume density (VD), and induction of peroxisomal enzymes
      and CYP4A1. Only a relatively weak induction of PP was noted at a carcinogenic
      dosage in female mice. In contrast to rodent species, ingestion of up to 20
      mg/kg/day HAL by male and female Beagle dogs for 13 weeks failed to increase
      peroxisomal VD while causing only a slight increase in peroxisomal enzyme
      activity at the highest dosages. Oral administration of up to 30 mg/kg/day HAL by
      male and female Cynomolgus monkeys for 13 weeks failed to induce PP. While a
      direct relationship of PP with tumor formation, at least in mice, was not
      demonstrated, these data still support the concept that PP represents a potential
      marker of nongenotoxic tumorigenic activity, at some dosage, in rodents.

PMID- 8566488
TI  - Dibromoacetic acid affects reproductive competence and sperm quality in the male
      rat.
AB  - Recently, we demonstrated with short-duration tests that dibromoacetic acid
      (DBAA), a commonly occurring by-product of water disinfection, alters sperm
      morphology and motility in the male rat. These results suggested that the effects
      of DBAA on sperm quality were likely to compromise reproductive competence of the
      male rat early in subchronic exposure. The present studies were undertaken to
      investigate the dose response and time course of alterations in fertility and
      sperm quality. Proven breeder male rats were gavaged daily with 0, 2, 10, 50, or
      250 mg DBAA/kg for up to 79 days; interim and terminal measurements of sperm
      quality and reproductive outcome were made. Because of the known neurotoxicity of
      the analogue, dichloroacetic acid, both natural breeding and artificial
      inseminations were evaluated in untreated females to distinguish between possible
      behavioral and spermatogenic effects. DBAA compromised male fertility during the
      second treatment week in naturally bred rats dosed with 250 mg/kg. The early
      antifertility effect appeared to be the result of behavioral changes since
      females artificially inseminated with sperm collected on Day 9 successfully
      produced offspring. However, sperm morphology and motility also were rapidly
      affected by DBAA treatment so that no offspring via natural insemination and only
      one litter via artificial insemination were produced subsequent to Day 15.
      Through 31 days, substantial effects on sperm motility, sperm morphology, and
      epididymal sperm numbers were observed, but there was no demonstrable effect on
      serum testosterone or sperm production. Because severe toxicity developed in the
      group given 250 mg/kg, exposure of these animals was prematurely terminated after
      42 doses and their recovery was monitored through a 6-month posttreatment period;
      decreased testis weights and only limited recovery of reproductive performance
      were observed. Exposure to 50 mg/kg resulted in moderate changes in sperm
      morphology and motility and moderate decreases in epididymal sperm counts in rats
      dosed for 31 or 79 days. However, these males remained fertile, litter size was
      unaffected, and no paternally mediated developmental defects were noted in their
      offspring. No effects on sperm quality were detected at dosages of 2 or 10 mg/kg.
      However, compared to controls, naturally bred DBAA-treated rats tended to have
      fewer inseminations, fewer copulatory plugs, and fewer multiple litters,
      suggesting that DBAA may have altered mating behavior at dosages as low as 10
      mg/kg.

PMID- 8566487
TI  - Chronic toxicity/oncogenicity of dimethylacetamide in rats and mice following
      inhalation exposure.
AB  - The potential chronic toxicity and oncogenicity of dimethylacetamide (DMAC) was
      evaluated by exposing male and female rats and mice to 0, 25, 100, or 350 ppm
      DMAC for 6 hr/day, 5 days/week for 18 months (mice) or 2 years (rats). Clinical
      pathology was evaluated at 3, 6, 12, 18, and 24 (rats only) months. An interim
      euthanization for rats occurred at 12 months and hepatic cell proliferation in
      rats and mice was examined at 2 weeks and 3 and 12 months. No compound-related
      effects on survival were observed. Rats exposed to 350 ppm had lower body weight
      and/or body weight gain. There were no compound-related effects on body weight or
      weight gain in mice at any concentration. There were no compound-related adverse
      effects on the incidence of clinical signs of toxicity in rats or mice. No
      hematologic changes were observed in either species. Serum sorbitol dehydrogenase
      activity was increased in rats exposed to 350 ppm. Serum cholesterol and glucose
      concentrations were significantly higher in 100 and 350 ppm female rats. Compound
      related morphological changes were observed in the liver. In rats, exposure to
      100 or 350 ppm produced increased absolute and/or relative liver weights, hepatic
      focal cystic degeneration, hepatic peliosis, biliary hyperplasia (350 ppm only),
      and lipofuscin/hemosiderin accumulation in Kupffer cells. In mice, exposure to
      100 or 350 ppm produced increased absolute and relative liver weights (350 ppm
      females only), accumulation lipofuscin/hemosiderin in Kupffer cells, and
      centrilobular single cell necrosis. Male rats exposed to 350 ppm also had
      significantly higher absolute and relative kidney weights which correlated with
      the gross and microscopic changes resulting from a compound-related increase in
      severity of chronic progressive nephropathy. Female mice exposed to 350 ppm had
      an increased incidence of bilateral, diffuse retinal atrophy. No increase in
      hepatic cell proliferation was seen in mice or rats at any exposure
      concentration. DMAC was not oncogenic under these experimental conditions in
      either the rat or mouse. The NOAEL for male and female rats and mice is 25 ppm.

PMID- 8566490
TI  - [Maintenance of vertical posture during simultaneous vibration of the calf and
      anterior tibial muscles].

PMID- 8566489
TI  - Metabolism and testicular toxicity of 1,3-dinitrobenzene in the rat: effect of
      route of administration.
AB  - Studies investigating the testicular toxicity of 1,3-dinitrobenzene (1,3-DNB)
      have utilized both the oral (po) and intraperitoneal (ip) routes of
      administration. These two administration routes could be expected to produce
      different pharmacokinetic profiles and, potentially, different degrees of
      toxicity. In the present work, the effect of route of administration upon 1,3-DNB
      disposition and susceptibility to testicular damage has been investigated. Male
      Sprague-Dawley rats were given 25 mg/kg 1,3-DNB either ip or po. Metabolites were
      quantitated in blood, urine, and feces, and methemoglobin levels were determined.
      Peak blood levels of 1,3-DNB and its major metabolite were three times higher in
      ip-dosed rats than in po-dosed rats. While the lower blood levels seen after po
      administration were maintained for greater than 6 hr, blood levels fell rapidly
      after ip dosing, reaching po levels at 6 hr postadministration. Peak
      methemoglobin levels in ip-dosed animals were twice that of po-dosed animals.
      Route of administration had a minor effect on the levels of urinary metabolites,
      while there was a significantly higher excretion of metabolites in the feces of
      po-dosed animals. Despite the markedly higher 1,3-DNB blood levels after ip
      administration, there were only subtle differences in testicular damage. The data
      raise the possibility that above a threshold level of 1,3-DNB in the blood, only
      the duration of testicular exposure to the toxicant may govern susceptibility to
      testicular toxicity.

PMID- 8566491
TI  - [Blood serum constants in a healthy person: response to space flight].

PMID- 8566492
TI  - [Removal of toxic substances from the body as a method for normalization of the
      functioning of the immune system].

PMID- 8566493
TI  - [Compliance of the arterial system in sportsmen].

PMID- 8566494
TI  - [Evaluation of the cardiorespiratory system while monitoring the functional state
      of a person].

PMID- 8566495
TI  - [Development of visual perception in early childhood].

PMID- 8566496
TI  - [Changes in slow rhythmic components of sphygmo- and electrocardiogram in the
      process of fatigue development].

PMID- 8566497
TI  - [A possible mechanism of the depressant effect of "medium molecules" on glucose
      metabolism in racing skiers].

PMID- 8566498
TI  - [Effect of a stationary focus of excitation in the limbic structures on the
      change in spatial-temporal organization of the human EEG].

PMID- 8566499
TI  - [Role of various zones of the cerebral cortex in man in the evaluation of changes
      in localization of a sound source].

PMID- 8566500
TI  - [Principles of integration of bioelectric activity of spatially distributed areas
      of the neocortex into a whole dynamic system].

PMID- 8566501
TI  - [Feasibility of directed rearrangement of human EEG parameters using adaptive
      biocontrol].

PMID- 8566502
TI  - [Dynamics of rhythmic components of the EEG alpha-band under conditions of
      relaxation].

PMID- 8566503
TI  - [Mechanisms of processing of unintentionally perceived visual information in
      children].

PMID- 8566504
TI  - [Psychophysiologic and autonomic parameters in sluggish and active youngsters
      (longitudinal studies)].

PMID- 8566505
TI  - [Psychophysiologic features of development in children of preschool age under
      various socio-ecologic conditions].

PMID- 8566506
TI  - [Hierarchy of memory trace processes and motor control].

PMID- 8566507
TI  - [Mechanisms of respiratory responses to external and internal resistive load].

PMID- 8566508
TI  - [Hormonal reorganization in sailors with varying levels of non-specific
      resistance].

PMID- 8566510
TI  - [Theoretical and clinical aspects of the problem of low-grade fever].

PMID- 8566509
TI  - [Effect of the lipid composition of the cell membrane on the domain structure of
      the bilayer and lateral transport].

PMID- 8566511
TI  - [Adaptive changes in autonomic functions in liquidators of the accident at the
      Chernobyl nuclear power plant in the process of conducting rehabilitation
      measures].

PMID- 8566512
TI  - [Correction of neuro-psychic maladjustment disorders using functional EEG
      biofeedback].

PMID- 8566513
TI  - [Typologic features of tonic components of cardiac rhythm].

PMID- 8566514
TI  - [Perception of image dimensions during persistent changes in emotional state].

PMID- 8566515
TI  - [Relationship between body temperature set point and erythrocyte size].

PMID- 8566516
TI  - [Temperature gradients of the upper and lower extremities in healthy people
      according to the results of radiothermometry studies].

PMID- 8566517
TI  - [Parameters of acid-base equilibrium and blood gases in the female body during
      the process of physiologic childbirth].

PMID- 8566518
TI  - [Features of the organization of the systems ensuring the higher functions of the
      brain].

PMID- 8566519
TI  - [EEG synchronization in man as affected by modulated illumination].

PMID- 8566520
TI  - [Classification, analysis and use of indicators of biological age for prediction
      of life expectancy].

PMID- 8566521
TI  - [Status of the hypophyseal-adrenal system in inhabitants of a large industrial
      city in Siberia].

PMID- 8566522
TI  - [Monitoring of the psychophysiologic potential of a population: methodologic
      potentialities for realization of the idea].

PMID- 8566523
TI  - [Seasonal and social influences on the cardiorespiratory system in inhabitants of
      the North].

PMID- 8566524
TI  - [Seasonal changes in physiologic functions in inhabitants of the North].

PMID- 8566525
TI  - [Circadian rhythm of secretion of electrolytes with saliva during acute human
      adaptation to contrasting climatic conditions in the environment].

PMID- 8566526
TI  - [Functional activity of the hypophyseal-thyroid system in pregnant women under
      conditions of the town of Khabarovska].

PMID- 8566527
TI  - [Prediction of health status and adaptation of workers in the gas-production
      industry under conditions of the arid zone].

PMID- 8566528
TI  - [The problem of human nutrition under the native-climatic conditions of
      Turkmenistan].

PMID- 8566529
TI  - Supervising the fold: functional principles of molecular chaperones.
AB  - Molecular chaperones are a set of conserved protein families that share the
      remarkable ability to recognize and selectively bind nonnative proteins under
      physiological and stress conditions. Thus, they prevent irreversible aggregation
      reactions and keep proteins on the productive folding pathway. Evidence suggests
      that the cell has developed several functionally distinct chaperone families to
      support protein folding. The importance of molecular chaperones under stress
      conditions is highlighted by the finding that all the major heat shock protein
      families (Hsp104, Hsp90, Hsp70, Hsp60/GroEL, and small Hsps) suppress
      irreversible unfolding reactions. Under heat shock, only the increased expression
      of a repertoire of different chaperones seems to convey thermotolerance and
      guarantee survival. The molecular mechanism by which chaperones in general
      influence protein folding processes is still far from clear. However, significant
      progress has been achieved in understanding some of the partial reactions of the
      chaperone folding cycles and in functionally differentiating between the
      different chaperone families.

PMID- 8566530
TI  - The molten globule state of alpha-lactalbumin.
AB  - The molten globule state of alpha-lactalbumin is the best-characterized folding
      intermediate of globular proteins and has been studied intensively by various
      spectroscopic and physiochemical techniques, including stopped-flow CD and
      fluorescence spectroscopies, a hydrogen-exchange technique, 1H-NMR spectroscopy,
      disulfide-exchange chemistry, site-directed mutagenesis, and calorimetric
      techniques. This review summarizes recent studies. Major findings about the
      structure of the molten globule state are: 1) It is highly heterogeneous, having
      a highly structured alpha-helical domain with the beta-sheet domain being
      significantly unfolded; and 2) it is not a nonspecific, collapsed polypeptide but
      already has a native-like tertiary fold. These structural characteristics are
      essential to fully understand the thermodynamic properties of the molten globule
      state which are described in connection with a recently proposed computational
      approach to predict the structure of the molten globule state of a protein.
      Mutant proteins in which the stability of the molten globule state was changed
      were constructed. Studies of the equilibrium unfolding and kinetic refolding of
      the mutant proteins will provide further insight into the molten globule state as
      a folding intermediate. In spite of an initial expectation that the structure
      recognized by an Escherichia coli chaperone, GroEL, is the molten globule, the
      interaction of GroEL with alpha-lactalbumin in the molten globule state is much
      weaker than the interaction with more unfolded states of alpha-lactalbumin, a
      disulfide-reduced form, and disulfide rearranged species.

PMID- 8566531
TI  - The roles of partly folded intermediates in protein folding.
AB  - Proteins can fold very rapidly, undoubtedly because they do not do so simply by
      random searching. The stable, partly folded species that can be detected during
      protein refolding are, however, of uncertain kinetic significance. The available
      kinetic evidence indicates that the intermediates that are most responsible for
      the rapidity of folding are extremely unstable and not populated detectably; they
      are less extreme versions of the transition state for folding. Protein folding is
      most readily studied when it is coupled to disulfide formation, which has the
      advantages that the intermediates can be characterized in detail and their
      kinetic roles determined unambiguously. The most important aspects of the
      disulfide folding pathway of BPTI are understood to at least a first
      approximation, and several other protein disulfide folding pathways are known in
      outline. These pathways demonstrate that disulfide folding is not intrinsically
      different from that not involving disulfide formation. Partly folded
      conformations can increase the rate of folding somewhat by causing productive
      disulfide bonds to be populated preferentially, but the most important folding
      intermediates are not detectable. The essence of folding is to build up the
      cooperativity between the individual interactions that is necessary for a stable
      conformation.

PMID- 8566532
TI  - Protein folding by a biased Monte Carlo procedure in the dihedral angle space.
AB  - A straightforward method for predicting the protein structure is to find
      conformations that have the lowest energy along a chosen folding pathway. One
      approach in this direction is to produce a large number of structures by varying
      the dihedral angles of the molecule more or less randomly and then to screen each
      one using a suitable energy function. This procedure is computationally
      demanding, but by using a more realistic model, one hopes that the folding
      behavior one observes in calculations may better mimic the actual folding process
      in nature. The method is beginning to yield interesting results, thanks to the
      increase in the computational power but also to the intelligent selection of the
      folding pathway. This article reviews general features of this method, some
      important highlights of the particular procedure we used, and some of the more
      significant results obtained to date in our laboratory. The results are highly
      encouraging and indicate the direction of future effort that is most likely to be
      fruitful.

PMID- 8566533
TI  - Assigning amino acid sequences to 3-dimensional protein folds.
AB  - With the advent of genome sequencing projects, the amino acid sequences of
      thousands of proteins are determined every year. Each of these protein sequences
      must be identified with its function and its 3-dimensional structure for us to
      gain a full understanding of the molecular biology of organisms. To meet this
      challenge, new methods are being developed for fold recognition, the
      computational assignment of newly determined amino acid sequences to 3
      dimensional protein structures. These methods start with a library of known 3
      dimensional target protein structures. The new probe sequence is then aligned to
      each target protein structure in the library and the compatibility of the
      sequence for that structure is scored. If a target structure is found to have a
      significantly high compatibility score, it is assumed that the probe sequence
      folds in much the same way as the target structure. The fundamental assumptions
      of this approach are that many different sequences fold in similar ways and there
      is a relatively high probability that a new sequence possesses a previously
      observed fold. We review various approaches to fold recognition and break down
      the process into its main steps: creation of a library of target folds;
      representation of the folds; alignment of the probe sequence to a target fold
      using a sequence-to-structure compatibility scoring function; and assessment of
      significance of compatibility. We emphasize that even though this new field of
      fold recognition has made rapid progress, technical problems remain to be solved
      in most of the steps. Standard benchmarks may help identify the problem steps and
      find solutions to the problems.

PMID- 8566534
TI  - Peptide mass fingerprinting of chaperonin-containing TCP-1 (CCT) and copurifying
      proteins.
AB  - The chaperonin-containing TCP-1 (CCT), found in the eukaryotic cytosol, is
      currently the focus of extensive research, CCT isolated from mouse testis lysate
      sediments at 20S in a sucrose gradient and accounts for about 70% of the total
      protein in this fraction. We intend to identify all the other proteins that
      copurify with CCT and to compile a reference profile for future studies. Their
      identification can be accelerated by a combination of protease digestion, matrix
      assisted laser desorption-mass spectrometry, and database matching known as
      peptide mass fingerprinting. We applied this strategy to 32 polypeptides resolved
      by 2-dimensional gel electrophoresis, and 23 known proteins and 6 novel proteins
      were identified. We analyzed isoelectric variants of the CCT subunits and
      differences in the peptide mass spectra of two CCT theta isoforms indicated a
      novel posttranslational modification of this subunit.

PMID- 8566535
TI  - In vivo protein folding: suppressor analysis of mutations in the groES
      cochaperone gene of Escherichia coli.
AB  - Our previous work has shown that the Escherichia coli groES14 and groES15
      mutations result in reduced GroE chaperone machine function. By selecting for
      restoration of the ability of those mutant groES alleles to suppress the
      thermosensitivity of bacteria bearing the dnaA46 mutation, we isolated a number
      of intra- and extragenic suppressors that increase in vivo GroE chaperone
      function. One of the intragenic suppressors has been mapped to a segment that
      codes for the GroES mobile loop, previously shown to be indispensable for proper
      GroES/GroEL interaction. Two extragenic suppressors have been mapped to a groEL
      segment, previously identified by mutational analysis as coding for an important
      functional region of the GroEL protein. Our results should contribute to our
      eventual understanding of the structure-function relationships of the universally
      conserved GroE chaperone machine.

PMID- 8566536
TI  - Unproductive folding of the human G6PD-deficient variant A-.
AB  - Human glucose-6-phosphate dehydrogenase (G6PD) deficiency almost invariably
      results from the presence of missense mutations in the X-linked gene encoding
      G6PD. The common African deficient variant G6PD A- differs from the normal G6PD B
      by two amino acid substitutions. Only one of these mutations is found on its own,
      resulting in the nondeficient variant G6PD A. Deficiency is always associated
      with decreased G6PD activity in red cells, leading to a variety of clinical
      manifestations. A group of deficient variants, including A-, have near-normal
      affinity for the substrates G6P and NADP. In these cases, deficiency is caused by
      a decreased number of catalytically active molecules per cell due to
      intracellular instability of the mutated G6PD, although the mechanism for this in
      vivo instability is unknown. Here we report that in vitro folding of the A-
      variant mainly renders partially folded polypeptides that do not undergo the
      dimerization required for activity. Under the same conditions, the nondeficient
      variants B and A undergo folding to produce active dimers with normal mobilities
      in native gels and normal kinetic properties. The loss of intrinsic folding
      determinants in the A- variant may underlie the mechanism of its in vivo
      instability.

PMID- 8566537
TI  - Second-site reversion of a structural defect in bacteriophage T4 lysozyme.
AB  - A plasmid-borne gene encoding bacteriophage T4 lysozyme with a structural
      mutation, Tyr161-Ala, was mutagenized by by the use of polymerase chain reaction.
      The mutagenized gene was inserted into a specialized bacteriophage lambda cloning
      vector that must acquire a functional lysozyme gene in order to form plaques.
      Functional variants of the mutant lysozyme were selected. Three compensatory
      second-site revertants were obtained: Thr152-Met, Lys43-Ile, and Thr151-Ala. The
      effects of these mutations are interpreted in light of previous structural and
      genetic studies of T4 lysozyme.

PMID- 8566538
TI  - Spectroscopic and volumetric investigation of cytochrome c unfolding at alkaline
      pH: characterization of the base-induced unfolded state at 25 degrees C.
AB  - We have measured at 25 degrees C the relative specific sound velocity increment,
      [u], and the partial specific volume, v degrees, of cytochrome c as a function of
      pH. Our data reveal that the base-induced native to unfolded transition of the
      protein is accompanied by a volume decrease of 0.014 cm3 g-1 and a
      compressibility decrease of 3.8 x 10(-6) cm3 g-1 bar-1. These results allow us to
      conclude that, relative to a fully unfolded conformation, the base-denatured
      state of cytochrome c has only 70 to 80% of its surface area exposed to the
      solvent. Recently, we reported a similar result for the acid-denatured state of
      cytochrome c. Thus, insofar as solvent exposure is concerned, both the base- and
      the acid-induced unfolded states of cytochrome c retain some order, with 20 to
      30% of their surface areas remaining solvent-inaccessible. We discuss the
      implications of this result in terms of defining potential intermediate states in
      protein folding pathways.

PMID- 8566539
TI  - Protein fold recognition by sequence threading: tools and assessment techniques.
AB  - Protein fold recognition has been approached by threading an amino acid sequence
      onto a library of folds, calculating a sequence-structure compatibility score,
      and ranking these scores. Due to imperfections in the empirically derived
      pairwise potential functions and the necessarily heuristic approach to the
      sequence-structure alignment problem, the method benefits from the assessment of
      threaded models to evaluate the most probable structures among the list of
      possible folds. THREADER and ANALYST, software tools available through the
      Internet, facilitate the alignment and assessment steps of a threading
      prediction. No process has been found to be universally reliable for the
      detection of folds related to the structure of a known input sequence, but
      several useful steps and approaches are discussed.

PMID- 8566540
TI  - From protein coagulation and reversible denaturation to the protein folding
      problem: Chris Anfinsen defining the transition.

PMID- 8566541
TI  - The structure and evolution of alpha/beta barrel proteins.

PMID- 8566542
TI  - Protein folding in the cell: competing models of chaperonin function.
AB  - The long-standing view that polypeptide chains newly synthesized inside cells
      fold spontaneously to their functional conformations in an energy-independent
      fashion derives from the observation that many pure denatured proteins will
      refold spontaneously in vitro when the denaturant is removed. This view is being
      challenged by the alternative proposal that in vivo many chains need to be helped
      to fold correctly by preexisting proteins acting as molecular chaperones, some of
      which hydrolyse ATP. The need for molecular chaperones arises because of the high
      concentrations of transiently interacting protein surfaces inside cells permit
      the formation of incorrect nonfunctional structures. The best-studied family of
      molecular chaperones are called the chaperonins, the archetypal examples being
      the GroEL and GroES proteins of Escherichia coli. The chaperonins increase the
      yield of correctly refolded polypeptide chains, both by decreasing their
      propensity to aggregate with one another and by allowing polypeptides kinetically
      trapped in incorrect conformations to make fresh attempts to refold into the
      functional conformations. The mechanisms by which the chaperonins achieve these
      remarkable results are currently under debate. This review surveys competing
      models for chaperonin action, and emphasizes the importance when evaluating these
      models of considering the intracellular environment in which the chaperonins have
      evolved to function.

PMID- 8566543
TI  - The denatured state (the other half of the folding equation) and its role in
      protein stability.
AB  - Experimental studies of the physical interactions that stabilize protein
      structure are complicated by the fact that proteins do not unfold to a simple
      reference state. When their folded structure breaks down, protein chains do not
      become random coils. Instead, they enter a poorly understood ensemble of
      partially folded states known collectively as the denatured state. Although it
      has long been held that agents that promote protein unfolding act specifically on
      the denatured state, the idea that mutations can exert their destabilizing (or in
      some cases, stabilizing) effects directly on this state is not widely accepted. A
      large body of thermodynamic data on mutant proteins plus a limited amount of
      structural information describing mutational effects on denatured states indicate
      that 1) the denatured state plays a central role in all aspects of protein
      stability, including mutant effects, and 2) a quantitative understanding of how
      amino acid sequence encodes protein structure will probably depend on a more
      complete picture of this complex, difficult-to-study state.

PMID- 8566544
TI  - A determinable but unresolved problem.

PMID- 8566545
TI  - Structural and genetic analysis of the folding and function of T4 lysozyme.
AB  - The combination of directed mutagenesis with high-resolution structure analysis
      has made it possible to systematically address fundamental questions of protein
      folding and stability. Here we briefly review some recent results in this area
      based on studies of the lysozyme of bacteriophage T4. Extended segments of the
      polypeptide chain can be substituted with alanine, suggesting that about 50%, or
      perhaps less, of the overall amino acid sequence protein is necessary to define
      the 3-dimensional structure of the protein. It is the internal residues that seem
      to be most important for folding and stability (although not necessarily for
      function). Substitutions within the core of the protein of large nonpolar side
      chains with smaller ones have been used to better understand the nature of
      hydrophobic stabilization. Mutants that produce the largest cavities within the
      protein tend to be most destabilizing, allowing the energy cost of cavity
      formation to be estimated. Small, nonpolar ligands bind within such cavities and
      restore some stability to the protein. Analogous, nonpolar ligands do not bind,
      however, providing evidence that water molecules do not bind with high occupancy
      within nonpolar cavities. In a further series of studies it has been possible to
      re-engineer the active site region of T4 lysozyme to change the catalytic
      mechanism of the enzyme.

PMID- 8566546
TI  - Sequence determinants of folding and stability for the P22 Arc repressor dimer.
AB  - The Arc repressor is a small, homodimeric protein. Studies of mutant proteins
      show that the side chains that form the hydrophobic core are the most important
      determinants of structure. A variety of hydrogen bonds and salt bridges also
      contribute to stabilization of the native structure, but these can often be
      replaced by hydrophobic interactions. The transition state for folding/unfolding
      is dimeric and contains a large amount of buried hydrophobic surface, but the
      beta-sheet of native Arc is not formed. Moreover, relatively little side chain
      information appears to be used in the transition state, suggesting that tight
      packing of the hydrophobic core and optimization of hydrogen-bond geometry are
      events that occur later in folding.

PMID- 8566547
TI  - In vitro folding of inclusion body proteins.
AB  - Insoluble, inactive inclusion bodies are frequently formed upon recombinant
      protein production in transformed microorganisms. These inclusion bodies, which
      contain the recombinant protein in an highly enriched form, can be isolated by
      solid/liquid separation. After solubilization, native proteins can be generated
      from the inactive material by using in vitro folding techniques. New folding
      procedures have been developed for efficient in vitro reconstitution of complex
      hydrophobic, multidomain, oligomeric, or highly disulfide-bonded proteins. These
      protocols take into account process parameters such as protein concentration,
      catalysis of disulfide bond formation, temperature, pH, and ionic strength, as
      well as specific solvent ingredients that reduce unproductive side reactions.
      Modification of the protein sequence has been exploited to improve in vitro
      folding.

PMID- 8566548
TI  - A quantitative assessment of the role of the chaperonin proteins in protein
      folding in vivo.
AB  - In vitro the chaperonin proteins, GroEL and GroES, facilitate the folding of some
      other proteins under conditions where that process does not occur spontaneously.
      Using values drawn from a number of such in vitro studies, together with the
      known rates of in vivo protein synthesis by Escherichia coli and the known
      quantities of GroEL and GroES in E. coli, an assessment of the general role of
      these proteins in protein folding in vivo has been made. Three specific cases are
      examined, where compelling evidence points to the involvement of the chaperonins;
      the in vivo folding of the bacteriophage coat protein during the burst phase of
      phage morphogenesis and of Rubisco during chloroplast development and during
      expression of recombinant Rubisco in E. coli. In each case the maximum in vitro
      rates are nearly sufficient to account for the observed in vivo rates of
      formation of the native protein. However, in general, there appears to be
      sufficient GroEL and GroES to facilitate the folding of no more than 5% of all of
      the proteins within E. coli.

PMID- 8566550
TI  - Thermodynamics of denaturation of staphylococcal nuclease mutants: an
      intermediate state in protein folding.
AB  - A valuable approach to understanding the forces that maintain protein structure
      is to analyze the thermodynamic effects of mutations on protein folding. The
      folding process is most often described using an energetic model that assumes a
      two-state transition between the native and denatured states. However, some
      results obtained using this approach for mutants of the protein staphylococcal
      nuclease have contradicted expectations from our current understanding of protein
      energetics. The application of differential scanning calorimetry to a set of
      mutant nuclease proteins allowed us to measure directly the effects of mutations
      on the enthalpy and heat capacity changes of unfolding, as well as on the
      cooperativity. We found that most of these effects can be understood with a three
      state model of folding including a distinct intermediate, but not with the two
      state model. Use of a three-state instead of a two-state model leads to large
      differences in conclusions about the stability effects of some mutations,
      suggesting that reevaluation of the effects of mutations on this and other
      proteins may be necessary to achieve an accurate description of folding
      energetics. The two-state assumption commonly used in protein stability studies
      may be an oversimplification in many cases.

PMID- 8566551
TI  - Forces contributing to the conformational stability of proteins.
AB  - For 35 years, the prevailing view has been that the hydrophobic effect is the
      dominant force in protein folding. The importance of hydrogen bonding was always
      clear, but whether it made a net favorable contribution to protein stability was
      not. Studies of mutant proteins have improved our understanding of the forces
      stabilizing proteins. They suggest that hydrogen bonding and the hydrophobic
      effect make large but comparable contributions to the stability of globular
      proteins.

PMID- 8566549
TI  - Thermolabile folding intermediates: inclusion body precursors and chaperonin
      substrates.
AB  - An unexpected aspect of the expression of cloned genes is the frequent failure of
      newly synthesized polypeptide chains to reach their native state, accumulating
      instead as insoluble inclusion bodies. Amyloid deposits represent a related state
      associated with a variety of human diseases. The critical folding intermediates
      at the juncture of productive folding and the off-pathway aggregation reaction
      have been identified for the phage P22 tailspike and coat proteins. Though the
      parallel beta coil tailspike is thermostable, an early intracellular folding
      intermediate is thermolabile. As the temperature of intracellular folding is
      increased, this species partitions to inclusion bodies, a kinetic trap within the
      cell. The earliest intermediates along the in vitro aggregation pathway,
      sequential multimers of the thermolabile folding intermediates, have been
      directly identified by native gel electrophoresis. Temperature-sensitive folding
      (tsf) mutations identify sites in the beta coil domain, which direct the
      junctional intermediate down the productive pathway. Global suppressors of tsf
      mutants inhibit the pathway to inclusion bodies, rescuing the mutant chains.
      These mutants identify sites important for avoiding aggregation. Coat folding
      intermediates also partition to inclusion bodies as temperature is increased.
      Coat tsf mutants are suppressed by overexpression of the GroE chaperonin,
      indicating that the thermolabile intermediate is a physiological substrate for
      GroE. We suggest that many proteins are likely to have thermolabile intermediates
      in their intracellular folding pathways, which will be precursors to inclusion
      body formation at elevated temperatures and therefore substrates for heat shock
      chaperonins.

PMID- 8566552
TI  - Stability and folding of ultrastable proteins: eye lens crystallins and enzymes
      from thermophiles.
AB  - Soluble globular proteins exhibit marginal stabilities, equivalent to only a few
      weak intermolecular interactions. Extreme conditions in the biosphere, as well as
      acute physiological stress, require either mutative adaptation or stabilization
      by accessory proteins or extrinsic factors such as metabolites, cofactors, or
      compatible solvent components. No general strategies of stabilization have yet
      been established. However, certain contributions to stability have been
      elucidated by analyzing extremely stable proteins, such as crystallins from the
      eye lens, or proteins from hyperthermophilic microorganisms. Relating the
      structure and stability of homologous proteins from mesophiles and extremophiles,
      it becomes clear that stability increments may accumulate from 1) local
      interactions, 2) secondary or supersecondary structure, 3) packing and docking of
      domains, 4) association of subunits, and 5) conjugation with prosthetic groups,
      carbohydrate moieties, or nucleic acids, etc. Single and multiple point
      mutations, nicking and swapping of folding units in domain proteins, grafting of
      linker peptides between domains, and dissociation-reassociation of oligomeric
      proteins give insight into the cumulative nature of protein stability and its
      relation to the hierarchy of protein structure and folding. In this review, beta
      gamma-crystallins and enzymes from hyperthermophilic microorganisms are used as
      models to discuss mechanisms of protein stabilization.

PMID- 8566553
TI  - Investigation of protein folding by mass spectrometry.
AB  - Mass spectrometry is emerging as one of the most exciting new techniques being
      applied to studies of protein folding. Recent developments in soft ionization
      techniques enable intact proteins to be generated in the gas phase from aqueous
      solution, and fragmentation methods are providing a means of obtaining sequence
      specific information. These techniques, particularly in combination with
      established methods such as NMR spectroscopy, allow the investigation of both
      covalent and noncovalent events that occur during refolding processes. One
      important type of application involves mass spectrometry in an analytical role,
      for example, in characterizing the products of oxidative refolding experiments.
      Mass spectrometry can also be used to reveal fundamentally new information about
      the conformational properties of folding intermediates, both in isolation and in
      complexes with molecular chaperones, through the exploitation of hydrogen
      deuterium exchange phenomena. Of particular interest is the insight this approach
      can provide into the cooperativity of structure formation and the distribution of
      intermediates at different steps along folding pathways. In this paper we
      describe recent insights into protein folding resulting from the application of
      mass spectrometry and discuss the future potential of the method for studies in
      this area.

PMID- 8566554
TI  - [For whom is the hepatitis A vaccination in 1995?].

PMID- 8566555
TI  - [Celioscopic treatment of cholelithiasis in benign acute biliary pancreatitis].
AB  - OBJECTIVES AND METHODS: To evaluate the laparoscopic treatment of cholelithiasis
      in mild acute gallstone pancreatitis, 35 patients with gallstone pancreatitis and
      less than 4 Ranson's prognostic signs at 48 h were retrospectively included.
      RESULTS: Eight patients underwent preoperative endoscopic retrograde
      cholangiopancreatography. Surgery was performed a median of 15 (range: 4-60) days
      after the onset of pancreatitis, and included laparoscopic cholecystectomy with
      intraoperative cholangiography that was successful in 30 out of 32 cases (93%). A
      common bile duct stone was present in 4 patients (11%). Conversion to open
      surgery was necessary in 3 patients (8%). Choledocholithiasis was successfully
      removed by laparoscopy in two cases, and by laparotomy and postoperative
      endoscopic sphincterotomy in one case each. CONCLUSION: Laparoscopic treatment
      can be recommended as the primary treatment within a few days after the onset of
      mild gallstone pancreatitis.

PMID- 8566556
TI  - [Sero-epidemiology of hepatitis A: alcoholic patients are a group at risk].
AB  - OBJECTIVES: The possibility of "community-acquired" viral infection has been
      suggested in alcoholics. In order to assess this hypothesis, we evaluated the
      prevalence of antibodies against hepatitis A virus, a oro-fecally transmitted
      virus, in heavy drinkers. PATIENTS AND METHODS: We retrospectively studied 258
      heavy drinkers, 188 males and 70 females, divided into sub-groups of increasing
      age, and compared them to 277 similarly classified blood donors. RESULTS: The
      prevalence of serum anti-hepatitis A antibodies was significantly higher in
      alcoholics than in controls (64.7 vs 52.3%, P < 0.01). The difference was
      particularly marked in patients younger than 45 years old (56.2 vs 39.1%, P <
      0.01). In the alcoholics, there was no correlation between the prevalence of anti
      hepatitis A antibodies and the socioeconomic level, the quantity of alcohol
      ingested, or the severity of the underlying liver disease. CONCLUSION: These
      results suggest that alcoholism is, per se, a risk factor for viral infections.

PMID- 8566557
TI  - [Hepatotoxicity of drugs. 8th updated bibliographic database of hepatic lesions
      and responsible drugs].

PMID- 8566558
TI  - [Stomach cancer: what's new?].

PMID- 8566559
TI  - [Epidemiology and prognosis of gastric carcinomas at the province of Calvados. A
      10-year study].
AB  - OBJECTIVES: The aim of this study was to determine trends in incidence and
      survival for gastric cancer in the department of Calvados over a ten-year period.
      METHODS: Between 1978 and 1987, 999 patients with gastric cancer were registered
      by the Registry of digestive tumours of Calvados. Standardized incidence rates
      were calculated for males and females and for each site of the tumour in two
      consecutive 5-year periods: period I: 1978-1982; period II: 1983-1987. Then
      prognostic factors were determined with univariate and multivariate methods.
      RESULTS: Global incidence rates were 15.7/100,000 in men, and 6.7/100,000 in
      women. Incidence rates of antropyloric carcinomas significantly decreased in
      women (period I: 3.6/100,000, period II: 2.1/100,000; P < 0.01). The incidence
      rate of cancer of the cardia did not change in men (period I: 2.7/100,000, period
      II: 2.9/100,000; NS) nor in women (period I: 0.6/100,000, period II: 0.3/100,000;
      NS). The ratio of early gastric cancer was respectively 8% and 9.2% (NS). The
      frequency of "signet ring" cells carcinomas increased from 20% during period I,
      to 34% during period II (P < 0.05). Overall 5-year survival rate was 16%; it was
      26.3% after resection, without significant change between the two periods (27%
      versus 24.4%). The multivariate study in gastric cancer after resection pointed
      out 5 prognostic factors: age over 75 years, invaded resection margins, lymph
      node involvement, metastases and parietal wall involvement. CONCLUSIONS: The
      results of this epidemiologic study in the department of Calvados indicate that
      a) the global prognosis of gastric cancer was poor and did not change over the 10
      years of the study; b) incidence rates of antropyloric carcinomas slightly
      decreased in women; c) rates of early gastric cancers did not increase.

PMID- 8566560
TI  - [Therapeutic management and survival of gastric adenocarcinoma in the province of
      Finistere between 1984 and 1989].
AB  - OBJECTIVES: The aim of this study was to analyze the evolution of treatment
      regimens and survival rates of stomach adenocarcinoma recorded in the Finistere
      cancer registry from 1984 to 1989. METHODS: In a population of 838,627
      inhabitants, 1,280 patients with a gastric cancer were registered; 1,164 patients
      (693 males and 471 females) had an adenocarcinoma. Survival rates were estimated
      by the actuarial method, and compared using the logrank test and the Cox model.
      RESULTS: Surgical resection was the main treatment for 661 patients (57%). The
      frequency of curative resection increased from 25% between 1984 and 1986 to 35%
      after 1986. Among the other patients, 39 (3%) were treated by chemotherapy and/or
      radiotherapy, and 53 patients (4%) by endoscopy alone; 253 patients had only
      symptomatic treatment. The survival rates of all patients were 43% at 1 year and
      20% at 5 years. The median survival was 9.2 +/- 0.6 months. In patients with
      cancer managed surgically, the factors associated with a better prognosis were
      young age, long duration of symptoms before diagnosis, ulcerated macroscopic
      aspect, limited tumour extension and curative surgical resection. In other
      patients, 2 factors were associated a with better prognosis: the absence of
      metastases and an endoscopic palliative treatment. CONCLUSIONS: Surgical
      resection is the main treatment of gastric adenocarcinoma. Although the frequency
      of surgery increased, the prognosis of gastric adenocarcinoma did not improve
      within this 6-year period.

PMID- 8566562
TI  - [Factors of gastroesophageal acid reflux in severe obesity].
AB  - OBJECTIVE: To study in morbid obesity the relationship between the degree of
      gastro-oesophageal reflux (GER) and the excess of body weight, or the related
      factors such as the energy intake or the fat distribution (waist-hip ratio).
      METHODS: In 20 morbid obese subjects (body weight: 125 +/- 32 kg) consulting in a
      weight-loss programme, anthropometric measurements, 3-hr oesophageal pHmetry,
      double isotope labelled meal for studying gastric emptying, study of gastric acid
      and pepsin secretions using PEG 4,000 as marker, and upper endoscopy were
      performed. RESULTS: Nine out of the 20 patients had more than 10 GER per 3-hr
      period. Seven patients had at least one GER symptom per day. In 6 patients, pH
      was under 4 for more than 10% of the time. The total number of GER and the number
      of GER of more than 5 min duration were correlated to the body mass index (P =
      0.016 and P < 0.05 respectively). The number of GER was also correlated to the
      android type of overweight (P < 0.03). These relationships persisted when sex,
      age, smoking, and obesity complications (such as diabetes) were taken into
      account. There was a positive correlation between the number of GER and energy
      and lipid intake (energy intake: 3,119 +/- 1,082 kcal/day; P < 0.003 for both).
      The degree of GER was positively related to basal acid output (P = 0.049), and to
      sham feeding-stimulated acid output (P = 0.05); it was negatively related to
      gastric emptying half time, but was not correlated with basal or stimulated
      pepsin output. A relationship was found between body mass index (BMI) and gastric
      emptying half time for solid (P = 0.002) and liquid phases (P = 0.001).
      CONCLUSION: GER seems to be common in long lasting morbid obesity. The number of
      refluxes increased with waist/hip ratio, BMI and energy or fat intake. GER was
      also increased by decreased gastric emptying rate, which was in part determined
      by BMI. The real prevalence of GER in morbid obeses must be determined by a large
      prospective study.

PMID- 8566561
TI  - [Effect of prolonged treatment with proton pump inhibitors on serum gastrin
      levels and the fundus mucosa. Preliminary results].
AB  - OBJECTIVES: To evaluate the evolution of fundic argyrophil cell density and
      hyperplasia grading, fundic chronic gastritis grading and serum gastrin levels in
      patients treated with proton pump inhibitors. METHODS: Thirty-two patients
      treated with proton pump inhibitors for gastroesophageal reflux and/or duodenal
      ulcer were studied. No patient had a gastric ulcer. The studied parameters were
      serum gastrin levels, fundic argyrophil cell density, the degree of fundic
      argyrophil cell hyperplasia, the grade of fundic atrophic gastritis and the
      presence of Helicobacter pylori. The first point of the study was 7 months
      (range: 0-42 months) and the last point 33 months (range: 7-72 months) after the
      beginning of the treatment. RESULTS: Serum gastrin levels significantly increased
      with treatment. Fundic argyrophil cell density did not change significantly. In 3
      patients (9%), serum gastrin levels were twice the normal upper limit. The
      highest serum gastrin levels (249 and 665 pg/mL) were noted in the 2 patients
      treated with the highest doses of proton pump inhibitors. Micronodular
      hyperplasia of the fundic argyrophil cells was observed in 2 patients treated
      with omeprazole 20 mg/d for 4 years and lansoprazole 90 mg/d for 6 years,
      respectively. Non active superficial chronic gastritis was noted in 2 patients.
      Serum gastrin levels were significantly correlated with cell densities.
      CONCLUSION: There were minor modifications of fundic argyrophil cell population
      and of gastrinaemia during the study period. They were not related to chronic
      atrophic gastritis. However, survey is mandatory in patients treated with high
      dose proton pump inhibitors, in those in whom gastrinaemia is elevated and when
      treatment duration is longer than 5 years.

PMID- 8566563
TI  - [Bone disorders in intestinal cryptogenetic inflammatory diseases].

PMID- 8566564
TI  - [Lichen planus and hepatitis C virus. Apropos of 5 new cases].
AB  - Lichen planus is an immunologically mediated skin or mucous disease, which has
      recently been described in some patients with hepatitis C virus-related liver
      disease. We report 5 new cases of the association of hepatitis C with lichen
      planus, to be added to the 15 cases published in the literature. The sex ratio
      (female/male) was of 1.2. Lichen planus occurred more frequently in chronic
      active hepatitis (2/3 of cases) than in cirrhosis (1/3 of cases). Lichen planus
      manifestations were only mucous (30%), only cutaneous (40%) or both (30%). Mucous
      lesions were mainly observed in patients with cirrhosis (3/4 of cases). The onset
      of skin and hepatic manifestations was variable, with liver disease as the most
      frequent revealing symptom (60%). The influence of interferon remains unclear.
      However, it seemed to trigger more than to relieve lichen planus.

PMID- 8566565
TI  - [Endoscopic treatment of a pancreatic-pleural fistula. Apropos of a case].
AB  - Pancreaticopleural fistula is a rare complication of pancreatic diseases. It
      results from communication between a pancreatic duct and the pleural space,
      either directly, or through a pseudocyst. The treatment is medical or surgical.
      We report a case of pancreaticopleural fistula occurring in a man suffering from
      chronic pancreatitis, and treated by endoscopy.

PMID- 8566566
TI  - [Dysphagia with fever revealing mediastinal lymph node tuberculosis. Apropos of 2
      cases].
AB  - The oesophagus is a rare localization of extrapulmonary tuberculosis. We report 2
      cases of tuberculous mediastinal lymph nodes revealed by dysphagia and fever in
      immunocompetent subjects. With the actual outbreak of tuberculosis, this
      localization is worth mentioning, as the precocity of the diagnosis and the
      therapeutic handling is an important prognostic factor.

PMID- 8566567
TI  - [Viral hepatitis A and exposure to sewage: a confirmed occupational risk].

PMID- 8566568
TI  - [Diffuse papillomatosis of the biliary and pancreatic ducts: a rare association
      and a potentially malignant disease].

PMID- 8566569
TI  - [Acute febrile polyarthritis and prolonged inflammatory syndrome in a patient
      with acute hepatitis A].

PMID- 8566570
TI  - [Serous cystadenoma of the pancreas revealed by choledochal stenosis].

PMID- 8566571
TI  - [Degenerative villous adenoma of the intrapancreatic choledochus].

PMID- 8566572
TI  - [Severe diarrhea with hypokalemia attributed to diacetylrhein].

PMID- 8566573
TI  - [Inflammatory disease of the upper digestive tract probably due to a synthetic
      progestational agent].

PMID- 8566574
TI  - [Adenocarcinoma of the anal glands].

PMID- 8566575
TI  - [Role of hepatitis B virus in the etiology of serologically silent viral
      hepatitis].

PMID- 8566576
TI  - [A new histological classification of cancers of the stomach].

PMID- 8566577
TI  - Risk and natural history of colonic neoplasia in patients with primary sclerosing
      cholangitis and ulcerative colitis.
AB  - BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) has been suggested as a
      risk factor for the development of colorectal cancer in ulcerative colitis (UC);
      however, previous studies of this association have been limited by small numbers
      of patients with PSC or have been performed retrospectively. This study
      prospectively evaluates the risk and natural history of colonic tumorigenesis in
      patients with PSC and UC and compares it with patients with UC without PSC.
      METHODS: Twenty patients with PSC and UC and 25 control patients with UC were
      followed prospectively by colonoscopic surveillance using extensive mucosal
      biopsy sampling. All control patients with UC had disease extending beyond the
      sigmoid colon of > or = 8 years' duration; patients with PSC and UC were studied
      regardless of disease duration. RESULTS: Forty-five percent (9 of 20) of the
      patients with PSC and UC had dysplasia compared with 16% (4 of 25) of the control
      patients with UC (P < or = 0.002). Prior liver transplantation did not affect the
      risk of colonic dysplasia. The time course for progression to dysplasia was
      similar between the patients with PSC and UC and the patients with UC; however,
      the patients with PSC and UC were five times more likely to develop dysplasia.
      CONCLUSIONS: Patients with PSC and UC represent a subset of patients with UC who
      are at markedly increased risk for colonic neoplasia and who need close
      colonoscopic surveillance with extensive biopsy sampling.

PMID- 8566578
TI  - Intestinal fatty acid-binding protein is a useful diagnostic marker for
      mesenteric infarction in humans.
AB  - BACKGROUND & AIMS: Acute ischemic diseases of the small bowel are lethal
      emergencies with no reliable diagnostic biochemical tests available. Experimental
      studies have suggested rat intestinal fatty acid-binding protein (I-FABP) as a
      serum marker reflecting bowel ischemia; the present study evaluates the human
      homologue (human I-FABP) as a serum marker for the diagnosis of acute ischemic
      diseases of the bowel. METHODS: Enzyme immunoassay was applied to determine I
      FABP levels in the sera of 96 subjects: 13 preoperative patients with ischemic
      bowel diseases (5 cases of mesenteric infarction and 8 cases of strangulated
      obstruction of the small bowel), 35 healthy subjects, and 48 hospitalized
      patients with acute abdominal pain. RESULTS: Serum I-FABP levels were < 65 ng/mL
      in healthy subjects. In patients with acute abdominal pain, levels ranged from <
      20 to 87 ng/mL (mean, 27.4 ng/mL), not significantly different from findings in
      healthy subjects. However, patients with ischemic bowel disease showed
      significantly higher I-FABP levels, ranging from < 20 to 1496 ng/mL (mean, 265.8
      ng/mL). All 5 patients with mesenteric infarction showed I-FABP levels of > 100
      ng/mL. CONCLUSIONS: I-FABP is a useful biochemical marker for the accurate
      diagnosis of mesenteric infarction.

PMID- 8566579
TI  - Interleukin 1 beta down-regulates collagen and augments collagenase expression in
      human intestinal smooth muscle cells.
AB  - BACKGROUND & AIMS: Smooth muscle cells resident in the intestinal wall play a
      significant role in the healing of the injured intestine and in the fibrosis that
      complicates Crohn's disease. The cytokine interleukin 1 beta (IL-1 beta) is
      involved in inflammatory bowel disease. The aim of this study was to determine
      the action of IL-1 beta on proliferation and collagen metabolism in human
      intestinal smooth muscle cells. RESULTS: IL-beta caused a three-fold increase in
      [3H]thymidine uptake at 100 pmol/L. This mitogenic effect was equipotent with
      that of platelet-derived growth factor when cells were exposed to IL-beta for 48
      vs. 24 hours. IL-beta inhibited the secretion of procollagen into culture medium
      by 70% and the accumulation of newly synthesized procollagen in cells by 55%. In
      addition, IL-beta caused a concentration-dependent inhibition of steady-state
      levels of procollagen I and III messenger RNA (85% inhibition at 100 pmol/L) and
      a 3-5-fold augmentation of collagenase messenger RNA levels. CONCLUSIONS: IL-beta
      is mitogenic for human intestinal smooth muscle cells, but this action is
      associated with a concomitant down-regulation of collagen synthesis and secretion
      and an augmention of collagenase expression.

PMID- 8566580
TI  - Intracolonic injection of glycerol: a model for abdominal pain in irritable bowel
      syndrome?
AB  - BACKGROUND & AIMS: Abdominal pain is the main symptom in patients with irritable
      bowel syndrome (IBS). Glycerol is an irritant of colonic mucosa. The aim of this
      study was to evaluate the effects of an intraluminal injection of glycerol on
      colonic motility and tone in patients with IBS and their modulation by drugs.
      METHODS: Colonic motility was evaluated using electromyography, and colonic tone
      was assessed using a barostat. Glycerol was injected in the right colon or the
      rectum. RESULTS: After intracolonic injection of glycerol, a strong abdominal
      colic occurred and was associated with an increase in long spike burst activity
      (+280%), which was eliminated by previous administration of lidocaine and was not
      observed after paraffin oil. When glycerol was injected intrarectally, abdominal
      pain occurred and long spike burst activity was increased (+240%) in the left
      colon. Simultaneously, colonic tone decreased (-70%) and high-amplitude phasic
      contractions occurred (10 +/- 1/patient). This rectocolonic reflex was
      reproducible in the same patient. Drugs acting on visceral afferent pathways
      (octreotide and granisetron) did not modify this reflex, whereas the spasmolytic
      drug phloroglucinol inhibited phasic contractions without affecting tone.
      CONCLUSIONS: Intraluminal injection of glycerol triggers viscerovisceral
      reflexes, resulting in abdominal pain in patients with IBS. It could be used as a
      model for the study of effects of drugs on pain in these patients.

PMID- 8566581
TI  - Expression of variant CD44-messenger RNA in colorectal adenocarcinomas and
      adenomatous polyps in humans.
AB  - BACKGROUND & AIMS: Recent studies have shown that some variant forms of CD44, a
      transmembrane glycoprotein expressed on various cell surfaces, might be involved
      in tumor progression or tumor metastasis. The aim of this study was to analyze
      the expression of CD44-messenger RNA (mRNA) in colorectal cancer and colorectal
      adenoma to further elucidate the role of CD44 in colorectal tumorigenesis.
      METHODS: The expression of CD44-mRNA was examined in 90 specimens from 44
      patients with colorectal cancer or colorectal adenomatous polyps and in the
      peripheral blood leukocytes from 7 healthy volunteers by reverse transcription
      polymerase chain reaction and Southern blot hybridization. RESULTS: Strong
      expression of the epithelial form and variant forms containing exons 11 or 12 of
      the CD44 gene, which conferred metastatic behavior to rat cells, was detected in
      primary and metastatic tumor tissues, whereas it was very weak or not detectable
      in normal colonic mucosae, normal liver tissue, or peripheral blood leukocytes.
      However, adenomatous colorectal polyps also showed as strong an expression of
      epithelial and variant forms of CD44 as primary and metastatic tumor tissues.
      CONCLUSIONS: These results suggest that variant forms of CD44-mRNA might be
      expressed in an early stage of colorectal carcinogenesis.

PMID- 8566582
TI  - Lipid islands in human gastric mucosa: morphological and immunohistochemical
      findings.
AB  - BACKGROUND & AIMS: Lipid islands are a common finding in the gastric mucosa, but
      their pathogenesis has not yet been established. The aim of this study was to
      investigate the morphology and immunophenotype of the various cells in lipid
      islands and to consider the possible mechanisms involved in the pathogenesis of
      these lesions. METHODS: Morphological and immunohistochemical investigations
      using antibodies against macrophages, smooth muscle cells, and lymphocytes were
      performed. Unfixed tissue was available for immunostaining for low-density
      lipoprotein (LDL) and oxidized LDL in one case. RESULTS: The lipid islands were
      composed of KP1-, KiM1p-, and cathepsin D-positive foam cells that were only
      weakly reactive for lysozyme. In cryostat sections, the foam cells were found to
      contain LDL and oxidized LDL. A few smooth muscle cells, plasma cells,
      lymphocytes, pericytes, fibroblasts, and Schwann cells that contained lipid
      droplets were also found. CONCLUSIONS: In gastric lipid islands, the presence of
      oxidized LDL, which is taken up by macrophages and smooth muscle cells via
      scavenger receptors, suggests that oxidized LDL is of key significance in the
      development and persistence of these lesions. Because the metabolism of LDL to
      oxidized LDL may occur by various mechanisms, various different initial
      conditions, including gastritis, may precede the development of lipid islands.
      Thus, anti-inflammatory treatment may be appropriate.

PMID- 8566583
TI  - High levels of transforming growth factor beta 1 in patients with colorectal
      cancer: association with disease progression.
AB  - BACKGROUND & AIMS: Contribution of transforming growth factor beta 1 (TGF-beta 1)
      to tumor progression has been suggested. However, little is known about the role
      of TGF-beta 1 in colorectal cancer. Plasma TGF-beta 1 levels and its expression
      were analyzed in patients with colorectal cancer. METHODS: Plasma TGF-beta 1
      levels were measured in 22 patients with colorectal cancer using a TGF-beta 1
      enzyme-linked immunosorbent assay. Expression of TGF-beta 1 messenger RNA and
      immunohistochemical distribution of the protein in colorectal cancer tissues were
      examined. RESULTS: Plasma TGF-beta 1 levels in patients with colorectal cancer
      (14.8 +/- 8.4 ng/mL) were significantly higher than in normal controls (1.9 +/-
      1.4; n = 22) (P < 0.001). After curative surgical resection, plasma TGF-beta 1
      levels decreased in examined patients from 11.9 +/- 6.7 to 3.8 +/- 1.2 ng/mL (P <
      0.01). TGF-beta 1 messenger RNA was about 2 1/2 times more abundant in colorectal
      cancer tissues than in control (P < 0.01). TGF-beta 1 was detected in the
      cytoplasm of colorectal cancer cells immunohistochemically. Both TGF-beta 1
      messenger RNA expression in colorectal adenocarcinoma tissues and its plasma
      levels were associated with tumor stage of Dukes' classification (P < 0.05).
      CONCLUSIONS: These results suggest that plasma TGF-beta 1 levels may reflect
      overexpression of the gene in colon cancer tissues and are associated with
      disease progression.

PMID- 8566584
TI  - Mechanisms of oral-pharyngeal dysphagia in patients with Parkinson's disease.
AB  - BACKGROUND & AIMS: Oral-pharyngeal dysphagia in Parkinson's disease is well
      recognized. The aim of this study was to establish the mechanisms of oral
      pharyngeal dysphagia in these patients. METHODS: Using simultaneous
      videoradiography and pharyngeal manometry, we studied 19 patients with
      Parkinson's disease (12 with oral-pharyngeal dysphagia and 7 without oral
      pharyngeal dysphagia) and compared them with 23 healthy controls. RESULTS: the
      clinical severity of Parkinson's disease predicted neither the presence nor the
      severity of dysphagia. Minor alterations in oral function were common in controls
      and patients, but pharyngeal dysfunction was significantly more prevalent in
      patients. Incomplete upper esophageal sphincter (UES) relaxation was present in 4
      patients (21%), all of whom showed increased hypopharyngeal intrabolus pressure,
      but not all of whom had a diminished UES opening. The patients had a reduced UES
      diameter (P = 0.004) and a higher intrabolus pressure compared with the controls
      (P = 0.007). Pharyngeal contraction pressures were lower in patients, but 6
      patients with dysphagia and an abnormal pharyngeal wall motion had normal peak
      pressures. CONCLUSIONS: An incomplete UES relaxation and a reduced UES opening,
      both associated with high intrabolus pressure, are prevalent in Parkinson's
      disease. Oral-pharyngeal dysphagia in Parkinson's disease is multifactorial, with
      the majority of patients showing oral and pharyngeal dysfunction, even before the
      clinical expression of dysphagia. Impaired pharyngeal bolus transport is the
      major determinant of dysphagia.

PMID- 8566585
TI  - Jejunal sensorimotor dysfunction in irritable bowel syndrome: clinical and
      psychosocial features.
AB  - BACKGROUND & AIMS: The interrelationships between enteric hypersensitivity,
      dysmotility, and psychosocial factors in the pathogenesis of irritable bowel
      syndrome (IBS) are poorly understood. The aims of this study were to (1) compare
      the clinical, jejunal motor, and psychological features in patients with IBS who
      have heightened sensitivity and those who have normal sensitivity to jejunal
      balloon distention and (2) examine psychosocial correlates of sensory and/or
      motor dysfunction. METHODS: Female patients with IBS (n = 24) and healthy
      controls (n = 9) underwent 24-hour ambulant duodenojejunal manometry, assessment
      of jejunal sensitivity by balloon distention, and comprehensive psychosocial
      assessment. RESULTS: In 6 (25%) and 10 (42%) patients, hypersensitivity was
      present at the threshold for initial perception and at the threshold for pain,
      respectively. After ingestion of a high-energy standard meal, all patients with
      heightened sensitivity for perception had abnormalities in the postprandial motor
      pattern compared with one third of patients with normal sensitivity. In this
      subgroup with hypersensitivity and postprandial dysmotility, clinical features
      were not discriminative but an inherently ineffectual coping style featuring both
      anger hyperreactivity and defensive control of anger was highly characteristic.
      CONCLUSIONS: In IBS, abnormal postprandial jejunal motor activity is related to
      jejunal mechanoreceptor-related hypersensitivity, and such sensorimotor
      dysfunction has a specific psychological profile.

PMID- 8566586
TI  - Relation between fat malabsorption and transit abnormalities in human carcinoid
      diarrhea.
AB  - BACKGROUND & AIMS: Fat and complex carbohydrates in the distal bowel activate
      "brakes" inhibiting upper gut motility. The hypothesis of this study was that
      rapid transit carcinoid diarrhea in association with steatorrhea results in
      impairment of gastric emptying. METHODS: Fifteen patients with carcinoid diarrhea
      without prior gastrointestinal resection or whose small bowel resection was
      limited to < 100 cm of ileum were studied. Gastrointestinal transit was measured
      scintigraphically with a standardized meal. Percentage of ingested fat excretion
      was calculated. RESULTS: Mean length of small bowel resected was 33 cm, and mean
      24-hour urine 5-hydroxyindoleacetic acid was 120 mg. Fourteen patients had
      increased daily stool weights, and 10 had increased stool fat excretion (mean,
      13%). Transit was accelerated in the small bowel in 14 and in the colon in all
      patients. The lag time for gastric emptying was prolonged in 2 patients who had
      no previous resection. Gastric emptying rate was accelerated in 5, normal in 7,
      and delayed in 3 patients. CONCLUSIONS: Ileal and colonic brakes do not seem to
      delay gastric emptying in patients with carcinoid diarrhea associated with rapid
      transit and mild to moderate steatorrhea.

PMID- 8566587
TI  - X-ray microanalysis of cell elements in normal and cystic fibrosis jejunum:
      evidence for chloride secretion in villi.
AB  - BACKGROUND & AIMS: Cystic fibrosis transmembrane conductance regulator (CFTR) is
      an adenosine 3',5'-cyclic monophosphate-dependent chloride channel that is
      defective in cystic fibrosis. The aims of this study were to determine if
      defective apical chloride secretion in the intestine of patients with cystic
      fibrosis alters the intracellular electrolyte milieu and to examine the
      geographical localization of CFTR in the normal intestine. METHODS: The content
      of intracellular elements was assessed in cryosections using energy-dispersive x
      ray microanalysis, and CFTR was identified by immunocytochemistry using
      commercially available antibodies. RESULTS: Cystic fibrosis jejunum had a
      significantly lower Na+ content, higher K+ and Cl- content, and higher
      potassium/phosphorus ratio in both villus and crypt regions. Incubation of normal
      jejunum with the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (300
      mumol/L) resulted in decreased K+ and Cl- content in both crypt and villus
      regions, indicative of Cl- secretion. CFTR was identified on the surface of
      normal villus and crypt enterocytes but not in cystic fibrosis samples.
      CONCLUSIONS: Defective apical chloride channels in cystic fibrosis result in
      alterations in the intracellular electrolyte milieu. The microanalysis
      observations and immunocytochemical studies imply a role for villus enterocytes
      in human intestinal chloride secretion.

PMID- 8566588
TI  - Inhibition of progressing primary esophageal peristalsis by pharyngeal water
      stimulation in humans.
AB  - BACKGROUND & AIMS: Sensory impulses initiated from the pharynx exert differing
      effects on the deglutitive apparatus. They have an inhibitory effect on the lower
      esophageal sphincter but an excitatory effect on the upper esophageal sphincter.
      The aim of this study was to systematically investigate the effect of pharyngeal
      sensory impulses evoked by water stimulation on the progressing esophageal
      peristalsis. METHODS: Sixteen healthy young volunteers were studied in the supine
      position. The presence of normal peristalsis was verified. Esophageal peristalsis
      was recorded 3, 6, 9, 12, 15, and 18 cm above the lower esophageal sphincter.
      Pharyngeal stimulation was performed by injecting a predetermined threshold
      volume into the pharynx 2 cm above the upper esophageal sphincter, directed
      posteriorly. The injections were timed to coincide with the arrival of the
      peristaltic wave induced by dry swallows at respective recording sites. RESULTS:
      Injection of the threshold volume (0.5 +/- 0.1 mL) stopped the progression of
      peristalsis at both the striated and smooth muscle esophagus. Topical pharyngeal
      anesthesia blocked this inhibitory effect (P < 0.01). CONCLUSIONS: Sensory
      impulses initiated from the pharynx evoked by water injection inhibit the
      progression of primary esophageal peristalsis. Although the clinical significance
      of these findings is not determined, they may explain the mechanism of some of
      the failed esophageal peristalsis.

PMID- 8566589
TI  - Effects of cigarette smoking on the long-term course of Crohn's disease.
AB  - BACKGROUND & AIMS: In Crohn's disease, smoking increases the risk for surgical
      procedures. The influence of smoking on the overall severity of the disease
      remains controversial. The purpose of the study was to examine the effects of
      smoking on the long-term course of Crohn's disease and the relationship between
      smoking and therapy. METHODS: The medical charts of 400 consecutive patients
      whose smoking habits were specified by direct interview were reviewed. RESULTS:
      Frequency and extent of excisional surgery were not significantly different in
      smokers and nonsmokers, but smokers required more glucocorticoids and
      immunosuppressive drugs. The effect of smoking on the need for immunosuppressive
      drugs was dose-dependent and was significant in women but not in men. For female
      smokers, the 10-year risk of immunosuppressive therapy was 52% +/- 11% compared
      with 24% +/- 10% for nonsmokers (P < 0.001). The risk of surgery increased only
      in patients who smoked and did not take immunosuppressive drugs. The surgical
      rate increased significantly during smoking in 19 patients who started smoking
      after diagnosis and decreased significantly in 34 patients who stopped compared
      with matched controls. CONCLUSIONS: Patients who smoke, particularly women and
      heavy smokers, run a high risk of developing severe disease. Immunosuppressive
      therapy neutralizes the influence of smoking on surgical rates.

PMID- 8566590
TI  - Risk of colorectal neoplasia in patients with primary sclerosing cholangitis.
AB  - BACKGROUND & AIMS: Studies implicating primary sclerosing cholangitis as a risk
      factor for colorectal neoplasia in patients with ulcerative colitis have been
      limited by small sample size and referral bias. The aim of this study was to
      determine the relative risk and cumulative incidence of colorectal neoplasia in a
      large sample of patients with sclerosing cholangitis. METHODS: A sample of
      patients with primary sclerosing cholangitis (n = 178), stratified by geographic
      area of residence, was identified and followed up to determine survival and
      development of colorectal neoplasia. The relative risk of colorectal cancer was
      determined using age- and sex-specific incidence rates of colorectal cancer in
      the U.S. general population as well as rates in patients with ulcerative colitis
      from central Sweden. RESULTS: The relative risk of colorectal cancer was elevated
      10-fold (standardized morbidity ratio, 10.3; 95% confidence interval, 2.1-30)
      compared with the general population for exposure to both sclerosing cholangitis
      and colitis but not cholangitis alone (standardized morbidity ratio, 4.9; 95%
      confidence interval, 0.1-27). The observed number of cancers was similar to that
      expected on the basis of rates in Swedish patients with ulcerative colitis.
      CONCLUSIONS: If primary sclerosing cholangitis is an additional risk factor for
      neoplasia in ulcerative colitis, the clinical significance of the risk seems to
      be low.

PMID- 8566591
TI  - Increased expression of keratinocyte growth factor messenger RNA associated with
      inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Alterations in intestinal epithelial cell function are common
      in inflammatory bowel disease (IBD). Keratinocyte growth factor (KGF) is an
      epithelial cell-specific mitogen. The aim of this study was to examine IBD tissue
      for altered KGF expression. METHODS: Expression levels of the KGF and KGF
      receptor transcripts were analyzed by ribonuclease protection assay. The cellular
      localization of each transcript was determined using in situ hybridization.
      RESULTS: KGF messenger RNA levels were increased in inflamed IBD tissue in
      comparison with control tissues. In normal tissue, KGF messenger RNA was
      localized to the mesenchymal cells at the tip of the villi in the small intestine
      and directly underlying the mature enterocytes in the colon, whereas in IBD it
      was present throughout the lamina propria, although distinct from the germinal
      centers. The topographic distribution of the KGF in situ hybridization signal in
      IBD was similar to that observed for T lymphocytes. In contrast, KGF receptor
      transcripts were localized to the cryptal region of the mucosal epithelium in
      both normal and IBD tissue, with no apparent differences in the level of
      expression. CONCLUSIONS: The increased expression of KGF in IBD suggests that it
      may be involved in mediating the altered regulatory functions of intestinal
      epithelial cells in this disease.

PMID- 8566592
TI  - Pathogenesis of gastric metaplasia of the human duodenum: role of Helicobacter
      pylori, gastric acid, and ulceration.
AB  - BACKGROUND & AIMS: The pathogenesis of gastric metaplasia (GM) in the duodenum is
      unclear. The aim of this investigation was to study the effect on the extent of
      GM of ulcer healing, Helicobacter pylori eradication, and acid suppression singly
      and in combination. The relationship between GM and gastroduodenal inflammation
      and H. pylori infection density was also studied. METHODS: Duodenal and gastric
      antral biopsy specimens were obtained from H. pylori-positive patients with
      duodenal ulcer and from H. pylori-positive nonulcer subjects. Biopsy procedures
      from patients with duodenal ulcer were repeated after 6 months of treatment.
      Nonulcer subjects were treated symptomatically and did not undergo re-endoscopy.
      RESULTS: Ulcer healing alone produced no change in GM or in gastroduodenal
      inflammation. H. pylori eradication produced a 42% reduction in GM and
      improvement in inflammation. Acid suppression produced a 43% reduction in GM but
      without a significant change in inflammation. A combination of H. pylori
      eradication and acid suppression produced an additive effect with a 66% reduction
      in GM. A positive relationship was detected between the extent of GM and antral
      H. pylori density, duodenitis score, and antral gastritis score. CONCLUSIONS:
      This study shows that the extent of duodenal GM is unrelated to the presence or
      absence of ulceration but is partly due to H. pylori and partly due to acid.

PMID- 8566593
TI  - Intestinal absorption of bile acids in the rabbit: different transport rates in
      jejunum and ileum.
AB  - BACKGROUND & AIMS: A direct comparison of jejunal and ileal absorption rates of
      bile acids has not been reported. The aim of this study was to compare the
      relative transport rates of different bile acids in the jejunum and ileum.
      METHODS: Jejunal and ileal rabbit intestinal segments were separately perfused
      with bile acid solutions, and dose-response curves were obtained for
      taurocholate, ursodeoxycholate, chenodeoxycholate, deoxycholate, and their
      glycoconjugates. Membrane fluidity and bile acid transport were assessed in brush
      border membrane vesicles. RESULTS: Taurocholate showed active transport in the
      ileum and no transport in the jejunum. Unconjugated bile acids showed passive
      diffusion in the two tracts, whereas glycoconjugated bile acids showed both
      components of transport in the ileum and passive diffusion in the jejunum (lower
      in the latter). A higher membrane fluidity and lower cholesterol-to-phospholipid
      ratio were found in the jejunum. Ursodeoxycholate reduced bile acid uptake into
      membrane vesicles from both ileum and jejunum. CONCLUSIONS: Active transport is
      limited to the ileum. Passive diffusion is higher through a less fluid membrane
      with a higher cholesterol-to-phospholipid ratio in the ileum than in the jejunum.
      Ursodeoxycholate inhibition may be at the level of a facilitated, sodium
      independent diffusion in the jejunum.

PMID- 8566594
TI  - Epidermal growth factor inhibits carbachol-stimulated canine parietal cell
      function via protein kinase C.
AB  - BACKGROUND & AIMS: Epidermal growth factor (EGF) inhibits secretagogue-stimulated
      gastric acid secretion via an EGF receptor located on parietal cells. The aim of
      this study was to examine whether this growth factor inhibited carbachol
      stimulated acid secretion through a protein kinase C-dependent mechanism.
      METHODS: The effect of EGF on carbachol-stimulated aminopyrine uptake, inositol
      trisphosphate formation, and intracellular Ca2+ ([Ca2+]i) in purified cultured
      parietal cells was studied. The ability of protein kinase A and C inhibitors to
      alter the inhibitory action of EGF was assessed. EGF-mediated translocation and
      activation of protein kinase C in parietal cells were determined. RESULTS: EGF
      dose dependently inhibited carbachol-stimulated aminopyrine uptake in a pertussis
      toxin-insensitive, genistein (tyrosine kinase inhibitor)--sensitive manner, with
      a maximal inhibitory effect (37.5% +/- 6.8%) achieved at 10(-7) mol/L. EGF did
      not significantly inhibit carbachol-stimulated inositol trisphosphate formation
      and did not alter the initial transient increase or sustained plateau in [Ca2+]i
      stimulated by this secretagogue. The protein kinase C inhibitors H-7 and
      staurosporine dose dependently reversed the inhibitory action of EGF, whereas H
      89 (protein kinase A inhibitor) failed to alter the effect of EGF. EGF
      pretreatment increased the translocation of alpha and beta 1 isoforms of protein
      kinase C and stimulated kinase activity in parietal cells. EGF did not down
      regulate the parietal cell muscarinic receptor. CONCLUSIONS: The inhibitory
      action of EGF on carbachol-stimulated parietal cell activity seems to involve
      protein kinase C.

PMID- 8566595
TI  - Immunolocalization of alkaline phosphatase and surfactant-like particle proteins
      in rat duodenum during fat absorption.
AB  - BACKGROUND & AIMS: In response to triacylglycerol feeding, rat duodenum secretes
      into the lumen and lamina propria phospholipid-rich membranes (surfactant-like
      particles) that are enriched with intestinal alkaline phosphatase. The purpose of
      this study was to determine whether the enzyme and particle proteins were
      coordinate in tissue distribution and in time. METHODS: Immunocytochemistry using
      specific polyclonal antisera against alkaline phosphatase and against the complex
      of particle proteins and its 40-kilodalton component was performed. RESULTS:
      Triacylglycerol feeding produced a peak between 3 and 5 hours in stain intensity
      for both antigens, intracellularly as well as in the paracellular space and
      lamina propria. In fasting animals, the microvillous membrane stained strongly
      for alkaline phosphatase; surfactant-like particle proteins were mainly localized
      to the lamina propria. Feeding Pluronic L-81 (BASF Wyandotte, Wyandotte, MI), a
      detergent that decreases transcellular triacylglycerol movement and surfactant
      like particle secretion, produced a decrease in reactivity of both antigens in
      the paracellular space, lamina propria, and lumen and redistributed intracellular
      alkaline phosphatase and surfactant-like particle proteins from Golgi or cytosol
      to intracellular membranes, corresponding to the circumference of lipid droplets.
      CONCLUSIONS: These data support the hypothesis that some intestinal alkaline
      phosphatase is secreted from the cell associated with the surfactant-like
      particle and are consistent with a role for this particle in transepithelial
      transport of triacylglycerols in the enterocyte.

PMID- 8566596
TI  - Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric
      injury in rats.
AB  - BACKGROUND & AIMS: The trefoil factors, a family of proteins abundantly expressed
      in gastrointestinal mucous cells, protect the epithelium in vitro. This study
      determines the effects of exogenously administered trefoil peptides on
      experimental injury in rats in vivo. METHODS: Gastric injury was induced by
      either intragastric absolute ethanol (1.0 mL) or subcutaneous indomethacin (20
      mg/kg). Recombinant human spasmolytic polypeptide (rHSP) or rat intestinal
      trefoil factor (ITF) were administered at different doses and time points before
      or after injury. Vehicle or bovine serum albumin was used as control. The pH of
      the stomach contents was assessed when the rats were killed. Gastric injury was
      blindly evaluated macroscopically and histologically. Serum levels of rHSP and
      ITF were determined by an enzyme-linked immunosorbent assay. RESULTS: Oral rHSP
      and ITF markedly protected against both ethanol- and indomethacin-induced gastric
      injury (P < 0.005 at doses of 1-15 mg/rat) when given up to 2 hours before
      injury; no protection was noted by intraperitoneal rHSP against ethanol injury.
      Intraperitoneal rHSP protected against indomethacin-induced injury only at the
      maximal dose given (15 mg). Neither rHSP nor ITF altered gastric pH. Protection
      was not associated with systemic absorption of trefoil peptides. CONCLUSIONS:
      Topical trefoil peptides protect the gastric mucosa against ethanol- and
      indomethacin-induced gastric injuries. These peptides contribute to surface
      mucosal defense.

PMID- 8566597
TI  - gamma-Aminobutyric acid stimulates electrolyte transport in the guinea pig ileum
      in vitro.
AB  - BACKGROUND & AIMS: An extensive enteric distribution of GABAergic neurons and
      nerve fibers has been identified in a number of species, including humans, but
      the role of gamma-aminobutyric acid (GABA) in mucosal physiology is unclear. The
      study was designed to determine if GABA stimulates electrolyte transport in an in
      vitro guinea pig ileum model. METHODS: The localization of GABAergic innervation
      in the submucosa and mucosa was determined using autoradiography. The effects of
      GABA and its analogues on electrolyte transport were measured in stripped guinea
      pig ileum mounted in Ussing chambers. Sensory afferent-evoked secretion after
      GABAA receptor blockade was also assessed. RESULTS: GABA and the GABAA receptor
      agonist 3-amino-1-propanesulfonic acid, but not the GABAB agonist baclofen,
      caused a bicuculline- and tetrodotoxin-sensitive, biphasic increase in short
      circuit current. The response to 3-amino-1-propanesulfonic acid was partially
      reduced by atropine, implicating cholinergic secretomotor neurons, and by the
      histamine H1 antagonist pyrilamine, suggesting the involvement of a histamine
      releasing cell. The GABAA receptor antagonist bicuculline and 3-amino-1
      propanesulfonic acid-induced tachyphylaxis, but not the GABAA-associated chloride
      channel blocker picrotoxinin, caused a modest reduction in the secretory
      responses to capsaicin. CONCLUSIONS: Activation of submucosal GABAA receptors
      elicits a multifactorial secretory response but plays a minor role in capsaicin
      sensitive, afferent-evoked secretion.

PMID- 8566598
TI  - Wheat bran suppresses potato starch--potentiated colorectal tumorigenesis at the
      aberrant crypt stage in a rat model.
AB  - BACKGROUND & AIMS: Starch that escapes digestion in the small intestine
      (resistant starch [RS]) may act similarly to nonstarch polysaccharides in the
      colon. The aim of this study was to examine the effect of raw potato starch alone
      and in combination with wheat bran on tumor development and precancer events in a
      rat model of colorectal cancer. METHODS: Three groups of rats received either a
      low-RS/low-fiber ("basic") diet, the basic diet containing raw potato starch as
      20% of carbohydrate content, or the potato starch diet plus 10% of "wheat bran"
      fiber. Epithelial proliferation, aberrant crypt foci (ACF), and tumors were
      measured 6 and 20 weeks after a 10-week course of dimethylhydrazine. RESULTS:
      Rats on the potato starch diet had tumors more frequently and had larger tumors
      than rats consuming the wheat bran or basic diets. Parallel effects on the
      density of ACF were found 6 weeks after the carcinogen. Although epithelial
      proliferation was significantly enhanced by potato starch compared with the basic
      diet, the addition of wheat bran did not suppress this enhancement. CONCLUSIONS:
      This type-2 RS enhances epithelial proliferation, ACF density, and tumor
      formation. The addition of wheat bran to an RS-containing diet suppresses
      tumorigenesis, acting on events responsible for the formation of ACF but not the
      events controlling the hyperproliferative phase.

PMID- 8566599
TI  - Cytosolic distribution of villin in M cells from mouse Peyer's patches correlates
      with the absence of a brush border.
AB  - BACKGROUND & AIMS: The follicle-associated epithelium (FAE) of Peyer's patches
      mainly consists of two cell types: absorptive enterocytes with a brush border and
      M cells without this apical specialization. To study the controversial ontogeny
      of M cells (mesenchymal vs. epithelial origin), the expression pattern of tissue
      specific cytoskeletal proteins, markers of cell origin that play a crucial role
      in the specific shape of epithelial cells and brush border assembly, was
      investigated. METHODS: The localization of cytokeratins, vimentin, and villin was
      determined on mouse FAE using immunocytochemistry and electron microscopy.
      RESULTS: Epithelial-specific cytokeratins were expressed in both absorptive
      enterocytes and M cells, whereas vimentin was not detected in mouse FAE. Villin,
      a tissue-specific, actin-binding protein of the brush border, was expressed in
      the two cell types. This protein had an unusual cytoplasmic distribution in FAE
      cells lacking a brush border and in cells having an intraepithelial pocket filled
      with lymphocytes. CONCLUSIONS: The presence of villin and the absence of vimentin
      in M cells support the intestinal origin of M cells. The cytoplasmic distribution
      of villin provides a new identification criteria for M cells and reflects the
      reorganization of the F-actin network, which correlates with the inability of M
      cells to assemble a brush border.

PMID- 8566600
TI  - Vascular adhesion protein 1 mediates binding of T cells to human hepatic
      endothelium.
AB  - BACKGROUND & AIMS: Molecules that regulate T-cell adhesion to hepatic endothelium
      and thereby recirculation of T cells to the liver are poorly understood. Because
      the adhesion molecule vascular adhesion protein-1 (VAP-1), which mediates
      lymphocyte binding to lymph node endothelium, is expressed on hepatic
      endothelium, it could play a role in regulating T-cell recruitment to the liver.
      The aim of this study was to investigate the distribution of VAP-1 expression in
      human liver and the ability of VAP-1 to support T-cell binding to hepatic
      endothelium in vitro. METHODS: Hepatic VAP-1 expression was investigated using
      immunohistochemistry and specific monoclonal antibodies, and VAP-1-mediated
      adhesion to hepatic endothelium was investigated with a tissue-binding adhesion
      assay using human liver sections. RESULTS: VAP-1 was expressed on sinusoidal and
      vascular endothelium in non-inflamed liver and in inflamed liver from patients
      with either allograft rejection or primary biliary cirrhosis. T cells from
      healthy donors bound to hepatic endothelium when added to noninflamed liver
      sections; this binding was inhibited by a specific anti-VAP-1 antibody but not by
      antibodies to intercellular adhesion molecule 1, lymphocyte function--associated
      antigen 1, or very late after activation (antigen) 4. VAP-1--mediated adhesion
      was unaffected by T-cell activation with phorbol ester. CONCLUSIONS: VAP-1 is
      constitutively expressed on hepatic endothelium and mediates T-cell adhesion to
      hepatic endothelium in vitro. VAP-1 could play a critical role in regulating T
      cell recirculation to the liver in vivo.

PMID- 8566601
TI  - Randomized comparison of ligation versus ligation plus sclerotherapy in patients
      with bleeding esophageal varices.
AB  - BACKGROUND & AIMS: Combining endoscopic sclerotherapy with ligation has been
      proposed to hasten variceal eradication. A randomized trial was performed
      comparing combination ligation plus sclerotherapy with ligation alone in patients
      with major bleeding from esophageal varices. METHODS: Forty-one patients were
      randomly assigned to receive ligation or ligation plus 1 mL 1.5% tetradecyl
      injected just above each band. Treatment was repeated weekly until varices were
      eradicated. Repeat endoscopy was performed for rebleeding and every 3 months
      after eradication. RESULTS: No significant differences were found between
      combined therapy and ligation in rebleeding (29% vs. 30%), blood transfused (3.1
      +/- 1.1 vs. 2.0 +/- 0.8 U), hospital days (9.3 +/- 2.1 vs. 7.5 +/- 1.2),
      complications (29% vs. 10%), or deaths (14% vs. 15%) during a mean follow-up
      period of 28 weeks. Combined therapy required significantly more sessions to
      achieve eradication (4.9 +/- 0.6 vs. 2.7 +/- 0.4) and greater time per treatment
      session (18.3 +/- 1.7 vs. 13.3 +/- 0.5 minutes). CONCLUSIONS: Combined ligation
      plus sclerotherapy does not reduce the number of treatment sessions required for
      variceal eradication as compared with ligation alone. Combined therapy lengthens
      the time required for treatment without improving efficacy or decreasing
      complications. Thus, combined ligation and sclerotherapy should not be used to
      treat patients with bleeding esophageal varices.

PMID- 8566602
TI  - Endothelin 1 is overexpressed in human cirrhotic liver and exerts multiple
      effects on activated hepatic stellate cells.
AB  - BACKGROUND & AIMS: Endothelin (ET) 1 could be involved in the regulation of
      hepatic microcirculation and in the development of portal hypertension. The
      expression and distribution of ET-1 in normal and cirrhotic liver tissue and its
      effects on hepatic stellate cells (HSCs), liver-specific pericytes, were
      investigated. METHODS: ET-1 expression in liver tissue was analyzed using in situ
      hybridization and immunohistochemistry. Secretion of ET-1 by HSC was evaluated by
      radioimmunoassay. Changes in intracellular Ca2+ concentration and cell
      contraction were studied using digital video imaging. Specific binding of ET-1
      was evaluated using self- and cross-displacement curves. RESULTS: ET-1 expression
      was markedly enhanced in cirrhotic liver tissue, where activated HSCs were shown
      to be major sites of ET-1 synthesis, as confirmed by studies performed on
      cultured human HSC. ET-1 exerted several biological actions on HSC, including
      mitogenicity, activation of mitogen-activated protein kinase, and a rapid
      increase in intracellular Ca2+ coupled with reversible cell contraction. All
      these effects appeared to be mediated by ETA receptors. Finally, the relative
      prevalence of ETA and ETB binding sites changed with the progressive phenotypical
      modulation of HSC. CONCLUSIONS: ET-1 may act as a paracrine and autocrine factor
      for activated HSC and contribute to the increased resistance to portal flow in
      cirrhotic liver.

PMID- 8566603
TI  - Portal hypertension activates the nitric oxide synthase genes in the esophageal
      mucosa of rats.
AB  - BACKGROUND & AIMS: Nitric oxide is associated with hyperdynamic circulation and
      development of collaterals in portal hypertension. The aim of this study was to
      investigate whether NO synthase is activated in the portal-hypertensive
      esophagus. METHODS: In esophageal specimens after portal ligation or sham
      operation, the expression of constitutive and inducible NO synthase messenger RNA
      was assessed by reverse transcription-polymerase chain reactions. NO synthase
      protein at 14 postoperative days was visualized with immunofluorescence staining
      with specific antibodies against constitutive and inducible NO synthase. RESULTS:
      The esophageal muscularis mucosae and epithelium overlying large submucosal veins
      in portal-hypertensive rats were significantly thinner than in controls
      (muscularis mucosae, 24.3% thinner, P < 0.01; epithelium, 23.0% thinner, P <
      0.05). Expression of NO synthase proteins in endothelia of submucosal veins was
      significantly higher in portal-hypertensive rats than in controls (constitutive
      NO synthase, 17.6%; inducible NO synthase, 18.0% increased over controls,
      respectively; P < 0.01). Expression of both constitutive and inducible NO
      synthase messenger RNA in portal-hypertensive rats was significantly increased
      (constitutive NO synthase, 10-fold; inducible NO synthase, 20-fold at 14 days vs.
      controls; P < 0.01). CONCLUSIONS: Portal hypertension triggers overexpression of
      NO synthase messenger RNA and protein in the rat esophageal mucosa. This
      phenomenon, combined with the thinness of muscularis mucosae and epithelium, may
      facilitate development and rupture of esophageal varices.

PMID- 8566604
TI  - Induction of the mitochondrial permeability transition by protease activity in
      rats: a mechanism of hepatocyte necrosis.
AB  - BACKGROUND & AIMS: The mitochondrial membrane permeability transition (MMPT) has
      been proposed as a mechanism of cell necrosis. In contrast, it has been suggested
      that enhanced activity of calpain-like proteases causes cell necrosis. To
      integrate these concepts, the hypothesis that stimulation of mitochondrial
      calpain-like protease activity induces the MMPT was developed. METHODS: Calpain
      like protease activity and the MMPT were measured in rat liver mitochondria. The
      mitochondrial membrane potential and cell necrosis were measured in rat
      hepatocytes. RESULTS: The protease inhibitor Cbz-Leu-Leu-Tyr-CHN2 inhibited both
      calpain-like protease activity and induction of the MMPT by Ca2+ and tert-butyl
      hydroperoxide. This effect of Cbz-Leu-Leu-Tyr-CHN2 was specific because serine,
      aspartate, and metalloprotease inhibitors did not inhibit the MMPT. The protease
      inhibitor Cbz-Leu-Leu-Tyr-CHN2 also delayed the onset of mitochondrial
      depolarization and cell necrosis during treatment of rat hepatocytes with tert
      butyl hydroperoxide, a model of oxidative stress relevant to human disease.
      CONCLUSIONS: These data suggest a unifying hypothesis linking calpain-like
      protease activity to the MMPT in cell necrosis. We propose for the first time
      that activation of mitochondrial calpain-like protease activity can function as a
      cytolytic trigger initiating the MMPT in cell necrosis.

PMID- 8566605
TI  - Role of intraduodenal proteases in plasma cholecystokinin and pancreaticobiliary
      responses to protein and amino acids.
AB  - BACKGROUND & AIMS: The role of small intestinal proteolytic activity in the
      regulation of upper gastrointestinal function in humans is poorly understood. The
      aim of this study was to determine the importance of proteolytic activity for
      protein- or amino acid-induced cholecystokinin release and pancreaticobiliary
      secretion. METHODS: In 9 healthy subjects, saline was perfused intraduodenally
      for 3 hours either with or without the synthetic protease inhibitor camostate.
      During the last hour, albumin or amino acids in the same molecular composition as
      albumin were also perfused. RESULTS: Perfusion with camostate, in concentrations
      that abolished intraduodenal proteolytic activity, had no effect on unstimulated
      plasma cholecystokinin concentrations or gallbladder emptying, but markedly (P <
      0.05) increased unstimulated pancreatic enzyme output. Perfusion with protein
      distinctly stimulated cholecystokinin release, gallbladder emptying, and
      pancreatic enzyme output (P < 0.05). Perfusion with camostate resulted in
      significantly lower protein-stimulated plasma cholecystokinin, gallbladder, and
      pancreatic enzyme responses (P < 0.05). Perfusion with amino acids also
      stimulated plasma cholecystokinin, gallbladder emptying, and pancreatic enzyme
      output (P < 0.05). Camostate did not inhibit these values. CONCLUSIONS: This
      study shows that appropriate digestion of protein is required to stimulate plasma
      cholecystokinin release, gallbladder emptying, and pancreatic enzyme secretion in
      humans.

PMID- 8566606
TI  - Transforming growth factor beta promotes development of fibrosis after repeated
      courses of acute pancreatitis in mice.
AB  - BACKGROUND & AIMS: Transforming growth factor beta (TGF-beta) is a putative
      mediator of fibrosis in several chronic diseases. Recently, chronic pancreatitis
      was suggested to be related to acute pancreatitis in the so-called necrosis
      fibrosis sequence hypothesis. The present study investigated whether TGF-beta is
      able to promote chronic fibrosis after repeated courses of necrotizing acute
      pancreatitis induced by cerulein in mice. METHODS: Six episodes of acute
      pancreatitis were repeatedly induced at weekly intervals in mice receiving either
      recombinant TGF-beta (4 micrograms in 4 days) or excipient alone at each
      induction. One week after the last induction, pancreatic lesions and collagen
      deposition were histologically assessed. Expression of pancreatic fibronectin
      messenger RNA was also examined in both groups. RESULTS: TGF-beta had no
      influence on a single course of acute pancreatitis. After six courses of acute
      pancreatitis, only mild inflammatory changes were observed in the control group.
      In contrast, important areas of perilobular and intralobular fibrosis were
      observed adjacent to inflammatory and necrotic foci in the TGF-beta group.
      Fibronectin messenger RNA expression was significantly higher in this group.
      CONCLUSIONS: TGF-beta promotes development of pancreatic fibrosis after recurrent
      episodes of acute pancreatitis. This model of pancreatic fibrosis could be used
      as a model of chronic pancreatitis consistent with the necrosis-fibrosis sequence
      hypothesis.

PMID- 8566608
TI  - Magnetic resonance cholangiography: comparison with endoscopic retrograde
      cholangiopancreatography.
AB  - BACKGROUND & AIMS: Magnetic resonance cholangiography (MRC) is a noninvasive
      diagnostic modality capable of producing high-quality images of the biliary tree.
      The purpose of this study was to determine in a prospective, blinded fashion the
      sensitivity and specificity of three-dimensional fast spin-echo (3D FSE) MRC for
      the evaluation of biliary tract abnormalities. METHODS: Forty-six patients
      referred for elective direct cholangiography (45 endoscopic retrograde
      cholangiopancreatography and 1 percutaneous transhepatic cholangiography) were
      studied prospectively with 3D FSE MRC during a 1-year period. All images were
      interpreted blindly by two radiologists. The presence of dilatation, strictures,
      and intraductal abnormalities was recorded. Sensitivity and specificity of 3D FSE
      MRC were determined using findings on direct cholangiography as the gold
      standard. RESULTS: MRC images of diagnostic quality were obtained in 44 (95.7%)
      of the patients. Sensitivity for the detection of bile duct dilatation (n = 27),
      biliary strictures (n = 10), and intraductal abnormalities (n = 7) was 96.3%,
      90%, and 100%, respectively. In addition, the MRC showed 16 of 17 patients with
      normal bile ducts (specificity, 94.1%). CONCLUSIONS: MRC has a very high
      sensitivity and specificity in the evaluation of the biliary tract. Based on
      these data, we believe that the efficacy of MRC using 3D FSE is sufficient to
      warrant its use in the routine diagnosis of biliary tract disease.

PMID- 8566607
TI  - Decreased interleukin-2 production in murine acute pancreatitis: potential for
      immunomodulation.
AB  - BACKGROUND & AIMS: The role of the cytokine interleukin 2 (IL-2) has long been
      recognized as central to normal immunologic function and defense against
      infection after burns and trauma, but little effort has been directed towards its
      role in acute pancreatitis (AP), which also has a high mortality related to
      sepsis. This study investigated the potential role of IL-2 in mice with diet
      induced AP. METHODS: AP was induced in mice by 10 days of feeding a choline
      deficient, ethionine-supplemented diet. T-helper (CD4) cells were estimated, and
      T-cell mitogen-stimulated splenocyte proliferation and IL-2 production in vitro
      were measured on days 3, 7, and 10. RESULTS: Significant reduction in IL-2
      production was found on day 3 (32%; P < 0.05) and day 10 (48%; P < 0.005).
      Administration of intraperitoneal lipopolysaccharide on day 10 was associated
      with reduced IL-2 production (P < 0.025) 4 hours later and 90% mortality in
      animals with AP. In vivo therapy with recombinant IL-2 improved in vitro IL-2
      secretion (P < 0.05) and reduced lipopolysaccharide-induced mortality (P =
      0.036). CONCLUSIONS: Murine diet-induced AP is associated with impaired immune
      function and increased susceptibility to sepsis and may be a valuable tool in the
      investigation of immunomodulation in AP.

PMID- 8566609
TI  - Role of nitric oxide in induction of inflammatory fluid secretion by the mucosa
      of the feline gallbladder.
AB  - BACKGROUND & AIMS: Nitric oxide is synthesized from L-arginine and is metabolized
      to nitrate and nitrite. This study evaluates the effects of a pharmacological
      blockade of NO synthesis on fluid transport by the inflamed gallbladder mucosa.
      METHODS: Experiments were performed in cats with cholecystitis and in control
      animals. NO synthase activity was measured in gallbladder tissue; the enzyme was
      characterized by immunoblotting techniques and localized by immunofluorescence.
      Fluid transport and release of nitrate and nitrite by the gallbladder mucosa and
      bile and bile salt secretion from the liver were registered simultaneously in
      vivo. RESULTS: Fluid secretion in inflamed gallbladders was reversed to a net
      absorption in response to the NO synthase blockers N omega-nitro-L-arginine and
      aminoguanidine, and formation of nitrate was reduced. The effects were reversed
      by L-arginine. Increased levels of inducible NO synthase in inflamed gallbladders
      were shown by immunoblotting, by immunofluorescence (mainly in macrophages), and
      by Ca(2+)-independent [3H]citrulline formation from [3H]arginine. The NO synthase
      blockers had no effect on gallbladder fluid transport in normal gallbladders.
      CONCLUSIONS: Increased levels of inducible NO synthase activity are shown in
      inflamed gallbladders, and a pharmacological blockade of this enzyme blocks fluid
      secretion and decreases nitrate release from the mucosa.

PMID- 8566610
TI  - Accumulation of unconjugated bilirubin in cholesterol pellets implanted in swine
      gallbladders.
AB  - BACKGROUND & AIMS: Most cholesterol gallstones have a pigmented center, but it is
      unclear whether its presence is primary or secondary. This study was performed to
      determine if bilirubin would accumulate in a gallstone model consisting of
      cholesterol pellets. METHODS: Cholesterol was compressed into pellets at 2500
      psi, producing a pellet that behaved like human cholesterol gallstones in regard
      to penetration of solutes into the stone. Pellets were implanted into
      gallbladders of pigs and harvested after 4 weeks. Bilirubin species were measured
      by high-performance liquid chromatography. RESULTS: The proportions of bilirubin
      species in bile were not changed by the presence of pellets, i.e., diconjugates
      (mean +/- SD, 1.9% +/- 1.0% vs. 0.7% +/- 0.8%), monoconjugates (83.8% +/- 5.5%
      vs. 87.8% +/- 6.6%), and unconjugated bilirubin (14.2% +/- 5.3% vs. 11.5% +/-
      5.6%) were similar at the time of implantation and removal. The cut surfaces of
      the pellets were pigmented. Pellets contained 5.46 +/- 1.38 micrograms
      bilirubin/g sample at harvesting, and 98.6% +/- 2.3% of bilirubin in pellets was
      unconjugated. In in vitro studies, there was a large increase in unconjugated
      bilirubin in the bile. Pellets also became pigmented in vitro, but there was
      considerable variability in the bilirubin species present in the pellets.
      CONCLUSIONS: Unconjugated bilirubin accumulates in cholesterol pellets and
      pigments them. This provides a mechanism by which cholesterol gallstones could
      become secondarily pigmented.

PMID- 8566611
TI  - The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett.

PMID- 8566612
TI  - Controlled clinical trials: the controls are the key.

PMID- 8566613
TI  - Lipid islands of the stomach: an insular issue?

PMID- 8566614
TI  - Trefoil peptides: a novel modality to prevent gastric injury?

PMID- 8566615
TI  - Endoscopic therapy of bleeding esophageal varices: ligation is still the best.

PMID- 8566616
TI  - Cytokines and acute pancreatitis.

PMID- 8566617
TI  - Laser-induced fluorescence spectroscopy: somewhere over the rainbow.

PMID- 8566618
TI  - Nasogastric decompression following laparotomy.

PMID- 8566619
TI  - Introducing the CIC family of Cl- channels.

PMID- 8566620
TI  - Drug choice in preventing postoperative Crohn's disease.

PMID- 8566621
TI  - Screening for hemochromatosis: additional considerations.

PMID- 8566622
TI  - NSAID trials, sporadic adenomas, and conservative inferences.

PMID- 8566623
TI  - Chemosensitivity in irritable bowel syndrome.

PMID- 8566624
TI  - The ASGE guidelines for the appropriate use of upper gastrointestinal endoscopy
      in an open access system.
AB  - AIMS: This multicenter and prospective study was aimed at examining the
      appropriate use of upper gastrointestinal endoscopy in an open access system
      (primary endoscopy) using the American Society for Gastrointestinal Endoscopy
      (ASGE) guidelines. We also wished to see whether these guidelines can be easily
      used in clinical practice. MATERIALS AND METHODS: Three thousand four hundred
      fourteen upper gastrointestinal endoscopies performed in seven endoscopy units of
      different size were studied prospectively. The real indication, to be with the
      guidelines, was determined by the endoscopist before performing the examination,
      based on a patient's history. RESULTS: Seven hundred eighty-one (23%) endoscopies
      were "generally not indicated," according to ASGE guidelines, and were
      distributed as follows: follow-up of duodenal ulcer healing (33%), follow-up of
      other healed benign diseases (24%), surveillance of gastric atrophy, pernicious
      anemia, metaplasia, treated achalasia, and prior gastric intervention (14%),
      diagnosis of dyspepsia considered functional in origin (13%), and uncomplicated
      heartburn responding to medical therapy (7%). Endoscopies "generally not
      indicated" accounted for 23% in the bigger endoscopy units, 24% in the average
      sized units, and 22% in the smaller ones. They accounted for 32% when the
      examination was prescribed by family doctors, 17% when prescribed by internists,
      19% by surgeons, and 14% by gastroenterologists (p < 0.001). Eighty-six (2.5%)
      endoscopies were done for indications not provided in the guidelines.
      CONCLUSIONS: This study shows that ASGE guidelines are complete and easy to use
      and that the rate of inappropriate indications in an open access system can be
      considerable. They occurred mainly in the follow-up of healed benign disease and
      were more frequent when the examination was prescribed by the family doctor.

PMID- 8566625
TI  - Appropriateness of indications for diagnostic upper gastrointestinal endoscopy:
      association with relevant endoscopic disease.
AB  - BACKGROUND: Since the institution of open access endoscopy units there has been a
      considerable increase of referrals for UGI examinations. Therefore, guidelines
      for the appropriate use of UGI endoscopy are needed. METHODS: The outcome of
      first diagnostic UGI endoscopy was prospectively assessed for several referral
      indications in a consecutive series of 2900 patients. Indications were judged
      "appropriate" when significantly (p < 0.01) associated with clinically "relevant"
      endoscopic findings. RESULTS: The proportion of relevant disease for various
      indications was as follows: signs of UGI bleeding (42.2%); history of peptic
      ulcer (40.5%); dysphagia (31.9%), short-term (24.4%), and without therapy
      (20.9%). Relevant endoscopic findings were observed in 21.0% of dyspeptic
      patients aged 45 years or less, and in 25.3% of those older than 45 years of age.
      CONCLUSIONS: The generally approved alarm symptoms should be a reason to perform
      endoscopy without hesitation. Dyspeptic symptoms, despite adequate empiric
      treatment, as well as first dyspeptic symptoms in patients older than 45 years
      should also be a reason for endoscopic investigation. Our results support the
      strategy to treat patients younger than 45 years who have isolated dyspepsia by a
      limited course of antipeptic agents, provided that they are seen for re
      evaluation within 4 to 6 weeks.

PMID- 8566626
TI  - A prospective controlled evaluation of endoscopic detection of angiodysplasia and
      its association with aortic valve disease.
AB  - BACKGROUND: In view of controversy about the association of aortic stenosis and
      angiodysplasia of the gut, we performed a prospective, controlled study to
      evaluate the relationship between aortic valve disease and gastrointestinal
      angiodysplasia. METHODS: Forty patients who had endoscopy for clinical
      indications such as gastrointestinal bleeding, anemia, polyps, colon cancer, and
      dyspepsia, and who were found to have angiodysplasia of the gastrointestinal
      tract, underwent two-dimensional and Doppler echocardiography. Thirty-seven
      controls matched for age, sex, indication, and nature of endoscopic examination,
      but without angiodysplasia, underwent similar echocardiographic examination.
      RESULTS: None of the patients in either group had aortic stenosis. The prevalence
      of aortic sclerosis, aortic insufficiency, and low left ventricular ejection
      fraction was similar in patients with and without angiodysplasia. CONCLUSIONS:
      This study does not support the role of aortic valve disease as the cause of
      angiodysplasia of the gastrointestinal tract. A subgroup of patients with
      angiodysplasia with aortic sclerosis, with or without other valvular disease (but
      none with aortic stenosis), had increased prevalence of gastrointestinal bleeding
      when compared with controls. When aortic valve disease or decreased left
      ventricular ejection fraction were analyzed as independent predictors, none of
      them in and of itself appeared to be a factor in bleeding from these
      gastrointestinal lesions.

PMID- 8566627
TI  - Anemia increases gastric blood flow in noncirrhotic and cirrhotic patients.
AB  - BACKGROUND: Previous studies in rats have demonstrated that anemia induces a
      significant increment in gastric mucosal blood flow. In the present study, we
      investigated whether chronic anemia induces similar changes in gastric blood
      perfusion in humans, and if this effect is also present in cirrhotic patients in
      whom gastric blood flow is usually increased in basal conditions. METHODS:
      Gastric mucosal blood perfusion was assessed by means of laser-Doppler flowmetry
      and reflectance spectrophotometry applied through the endoscope. RESULTS: Anemia
      significantly increases laser-Doppler signal in cirrhotic (2.3 +/- 0.11 vs 2.9 +/
      0.22 volts, p < 0.05) and noncirrhotic patients (1.71 +/- 0.15 vs 2.24 +/- 0.17,
      p < 0.05). In anemic patients the index of hemoglobin concentration of the
      gastric mucosa, assessed by reflectance spectrophotometry, was significantly
      decreased in cirrhotic patients (107.6 +/- 4.7 vs 95.5 +/- 3.3, p < 0.05) and
      noncirrhotic patients (93.9 +/- 4.1 vs 76.1 +/- 4.2, p < 0.01), whereas the index
      of oxygen saturation was increased (36.7 +/- 0.7 vs 40.4 +/- 1.4, p = 0.05; and
      36.4 +/- 1.1 vs 43.2 +/- 1.9, p < 0.01, respectively). CONCLUSIONS: In
      conclusion, chronic anemia is associated with an enhanced gastric blood perfusion
      reflected by an increased laser-doppler signal and gastric mucosal oxygen index
      despite a decrease in gastric hemoglobin concentration. In cirrhotic patients,
      anemia promotes a further increment in its basal gastric hyperemia.

PMID- 8566628
TI  - Colonic mucosal changes in patients with liver cirrhosis.
AB  - BACKGROUND: Portal colopathy has been reported in patients with cirrhosis of the
      liver. The aim of this study is to evaluate colonic mucosal changes and their
      clinical significance. METHOD: Seventy-five cirrhotic patients with anemia and
      hemoccult-positive stool and 75 control subjects underwent endoscopic
      examinations of lower gastrointestinal tract. RESULT: Colonic ectasiae were found
      to be significantly more common in the 75 cirrhotic patients (80% with hepatitis
      B or C infection) than control subjects (84% vs 0, p < 0.0001). The lesions in 63
      cirrhotic patients were found throughout the entire colon. They included colonic
      telangiectasiae or angiodysplastic-like lesions in 56 (89%) patients, red spots
      in 14 (22%), features suggesting mild chronic colitis in 8 (13%), and midrectal
      colorectal varices in 10 (16%). Pathologic findings in patients with
      telangiectasiae or angiodysplastic-like lesions showed dilation of vessels (7 of
      9 patients) and edema of mucosa (6 of 9 patients). There was no correlation
      between the severity of cirrhosis, grade of esophageal varices, and the presence
      of colonic ectasiae. CONCLUSIONS: Our observations demonstrate that colonic
      mucosal changes commonly occur in cirrhotic patients with viral hepatitis. The
      risk of intermittent hemorrhage from colonic ectasiae should be considered in
      cirrhotic patients with anemia but without evidence of upper gastrointestinal
      bleeding. These characteristic lesions may represent a spectrum of portal in
      hypertensive intestinal vasculopathy.

PMID- 8566629
TI  - The effectiveness of simethicone in improving visibility during colonoscopy when
      given with a sodium phosphate solution: a double-bind randomized study.
AB  - BACKGROUND: Oral sodium phosphate solution is better tolerated than polyethylene
      glycol when used for colonoscopy preparation, but visibility of the lumen can be
      impaired because of the presence of bubbles. METHODS: We studied 86 patients
      receiving either simethicone (n = 42) or placebo (n = 44) in addition to oral
      sodium phosphate to determine if simethicone improved visibility during
      colonoscopy. Colonoscopy was performed by a single blinded investigator. Five
      areas of the colon (rectosigmoid, descending, transverse, ascending, and cecum)
      were assessed for the presence of bubbles on withdrawal of the endoscope. Bubbles
      were scored as follows: 0, minimal or none; 1, covering half the lumen; 2,
      covering the entire circumference; 3 filling the entire lumen. RESULTS: Thirteen
      patients in the placebo group and only one in the simethicone had significant
      bubbles ( > or = 1). Additionally, the mean bubble scores were greater in the
      placebo group in each region of the colon (p < or = 0.05 in rectosigmoid and
      ascending colon). CONCLUSIONS: This study indicates that taking simethicone with
      an oral sodium phosphate preparation can improve colonic visibility by
      diminishing the presence of bubbles. Better visualization could improve detection
      of mucosal pathologic lesions.

PMID- 8566630
TI  - Endoscopic intracorporeal laser lithotripsy of difficult common bile duct stones
      with a stone-recognition pulsed dye laser system.
AB  - BACKGROUND: Endoscopic retrograde intracorporeal lithotripsy with a stone
      recognition laser system seems to be a promising alternative in patients with
      difficult bile duct stones. METHOD: Sixteen patients with bile duct stones not
      suitable for endoscopic standard procedures underwent intracorporeal laser
      lithotripsy during a 3-month period. An average of 6800 (120 to 25000) discharges
      were applied with a power setting of 100 mJ. Inserting the laser fiber into a
      radiopaque marked catheter or into a balloon catheter guaranteed a successful
      location on the stone surface in 70% of all discharges. The automatic
      feedback/cut-off at the fiber is not in contact with the stone surface. RESULTS:
      Fragmentation was achieved in all cases. Complete bile duct clearance was reached
      in 14/16 cases. In two cases, remaining fragments passed spontaneously through
      the papilla as controlled by ERCP. Minor complications were noted in two patients
      (hemobilia, cholangitis). Complete recovery was achieved in both patients with
      conservative management. CONCLUSIONS: For a selected group of patients with
      difficult common bile duct stones, intracorporeal laser lithotripsy with a stone
      recognition laser system was found to be a highly effective and safe technique.

PMID- 8566631
TI  - Interobserver agreement and predictive value of endoscopic findings for H. pylori
      and gastritis in normal volunteers.
AB  - BACKGROUND: Endoscopic findings such as erythema are frequently labeled as
      gastritis. We sought to determine interobserver agreement for specific endoscopic
      features and assess the diagnostic value of features with good agreement for
      Helicobacter pylori and histologic gastritis. METHODS: Fifty-two healthy subjects
      without ulcers, erosions, or hemorrhages had a full endoscopy recorded on video
      tape. Biopsy specimens were examined for H. pylori and gastritis. Two
      endoscopists independently reviewed the tapes for predefined features (erythema,
      area gastricae, clefts, and nodularity) in the gastric body and antrum.
      Diagnostic value of endoscopic features with acceptable agreement (kappa > 0.40)
      was then determined for H. pylori and gastritis. RESULTS: Kappa was greater than
      0.40 only for prominent body area gastricae (0.49), body nodularity (0.65), and
      antral nodularity (0.68). For antral nodularity, sensitivity was 32%, specificity
      was 96%, and positive predictive value was 90% for H. pylori. when both antral
      nodularity and body area gastricae were both present, sensitivity was only 18%
      but specificity and positive predictive value were 100%. CIRCULATION:
      Interobserver agreement is poor for some features such as erythema labeled as
      gastritis. Antral nodularity is a fairly reproducible finding and is very
      specific, though not sensitive, for H. pylori gastritis.

PMID- 8566632
TI  - Helicobacter pylori in cirrhotic patients with peptic ulcer disease: a
      prospective, case controlled study.
AB  - BACKGROUND: There is an increased prevalence of peptic ulcer disease in patients
      with liver cirrhosis, but the role of Helicobacter pylori is unclear. METHODS:
      lgG antibodies against H. pylori were measured in 60 patients with compensated
      liver cirrhosis, in 60 sex- and age-matched patients with compensated liver
      cirrhosis, and in 60 normal controls. All patients received panendoscopic
      examinations to search for the evidence of esophageal varices, congestive
      gastropathy, and peptic ulcers. RESULTS: Duodenal ulcers were more common in
      compensated and decompensated cirrhotic patients (16.7% and 13.3%, respectively)
      than in normal controls (3.3%, p < 0.05). Gastric ulcers were more frequent in
      decompensated (15.0%) than compensated cirrhotic patients and normal controls
      (3.3% and 1.7%, respectively, p < 0.05). The prevalence of H. pylori was not
      statistically different among the three groups (normal 60.0%, compensated 61.7%,
      and decompensated, 75.0%; p > 0.05). The prevalence of H. pylori also showed no
      statistical differences in respect to duodenal ulceration (100%, 80%, and 87.5%,
      respectively, p > 0.05). The prevalence of H. pylori did not differ significantly
      in relation to the presence or absence of esophageal varices (68.4% vs 100% if no
      varices, p = 0.04) and in the presence of congestive gastropathy (50.0 vs 94.7%,
      p = 0.03). CONCLUSIONS: The prevalence of peptic ulcer was increased in cirrhotic
      patients, but the prevalence of H. pylori was similar in compensated cirrhotic
      patients, decompensated cirrhotic patients, and normal controls. The frequency of
      non-H. pylori-associated peptic ulcers in cirrhotic patients was increased in the
      presence of esophageal varices or congestive gastropathy.

PMID- 8566633
TI  - A randomized double-blind comparison of placebo, etodolac, and naproxen on
      gastrointestinal injury and prostaglandin production.
AB  - BACKGROUND: NSAIDs frequently cause gastrointestinal injury and increase the risk
      of ulcer complications. We compared an NSAID suggested to cause less gastric
      injury (etodolac) with a standard NSAID (naproxen) and a placebo in a 4-week
      double-blind trial assessing the effects on gastroduodenal injury, symptoms, and
      prostaglandin production in healthy volunteers. METHODS: Fifty-two healthy
      volunteers not taking NSAIDs, alcohol, antibiotics, bismuth, or anti-ulcer drugs:
      placebo, etodolac 400 mg, or naproxen 500 mg b.i.d. for 4 weeks. Endoscopies with
      biopsies were repeated at weeks 1 and 4. The number and dimensions of ulcers and
      erosions were recorded to quantitate injury. RESULTS: At week 1 the mean number
      and area of gastric ulcers per subject were greater with naproxen than placebo or
      etodolac (area: naproxen, 7.4 mm2; placebo, 0.6 mm2, p = 0.02 vs naproxen;
      etodolac, 2.1 mm2, p = 0.06 vs naproxen). Ulcer scores at week 4 were low and
      comparable in the three groups. The mean number and area of gastric erosions per
      subject were greatest with naproxen at both weeks 1 and 4 (week 4 area: naproxen,
      58.3 mm2; placebo, 29.0 mm2; etodolac, 13.9 mm2, p < 0.02, naproxen vs placebo
      and vs etodolac). Placebo injury was presumably due to biopsies at prior
      endoscopy. Gastric mucosal prostaglandin E2 production did not change
      significantly from baseline after 1 or 4 weeks of treatment with placebo or
      etodolac, but did decrease significantly with naproxen (week 0, 1689; week 1,
      479; week 4, 577 pg/mg protein). Gastrointestinal symptoms were present in only 1
      (5%) of 20 visits in which endoscopy showed no erosions or ulcers vs 21 (26%) of
      82 visits in which a mucosal defect was identified (p = 0.666). CONCLUSION:
      Gastric injury with 4 weeks of etodolac is comparable to that seen with placebo
      and significantly less than that occurring with naproxen, presumably due to the
      fact that etodolac does not suppress gastric mucosal prostaglandin production,
      whereas naproxen leads to a significant reduction.

PMID- 8566634
TI  - Sensitivity of percutaneous endoscopy compared with ultrasonography in the
      detection of residue or mucosal lesions after topical gallbladder stone
      dissolution.
AB  - BACKGROUND: Early gallstone recurrence in some patients after "successful"
      percutaneous topical dissolution may be due to residual debris. An endoscope
      small enough to be introduced without dilating the existing percutaneous track
      was used for gallbladder examination after stone dissolution. METHODS: The
      sensitivity of gallbladder endoscopy was compared with ultrasonography and double
      contrast cholecystography for the detection of residual debris or mucosal lesions
      in 18 patients who underwent percutaneous topical dissolution. All examinations
      were performed before catheter removal and after the gallbladder was deemed stone
      free by the traditionally employed technique of single-contrast cholecystography.
      RESULTS: Residual debris was detected in only one patient by ultrasonography and
      in none of the 18 patients by double-contrast cholecystography, yet endoscopy
      showed stone fragments ranging from 1 to 3 mm in 13 of the 18 patients. In all
      these patients, catheter repositioning and additional solvent perfusion resulted
      in elimination of the debris as assessed endoscopically. Two patients had
      endoscopically detected erosions. Double-contrast fluoroscopy found only one of
      these, whereas ultrasonography detected neither. CONCLUSIONS: Percutaneous
      gallbladder endoscopy is a more sensitive imaging modality for the detection of
      residual stone debris or mucosal lesions after gallstone dissolution.

PMID- 8566635
TI  - Biliary IgA secretion in obstructive jaundice: the effects of endoscopic
      drainage.
AB  - BACKGROUND: Immunoglobulin A is the predominant immunoglobulin in the bile. Data
      on the effects of biliary obstruction on IgA secretion are few. METHODS: The
      serum and bile IgA levels in patients with common duct stones (n = 27) or with
      malignant obstructive jaundice (n = 20) were collected by insertion of
      nasobiliary catheters. Single samples of common duct bile from patients with
      gallstones (n = 24) were collected as controls. Bile samples collected were
      measured for total IgA, secretory IgA, and free secretory component levels by
      sandwich enzyme-linked immunosorbent assays. RESULTS: Bile total IgA, secretory
      IgA, and free secretory component in the common duct stones group (82.7 +/- 11.4
      microgram/ml, 18.4 +/- 1.7 microgram/ml, 0.74 +/- 0.15 microgram/ml) and the
      malignant obstructive jaundice group (81.6 +/- 10.7 microgram/ml, 18.2 +/- 2.4
      microgram/ml, 0.57 +2- 0.12 microgram/ml) were found to be significantly lower
      than those of the control gallstone patients (104.8 +/- 3.4 microgram/ml, 33.2 +/
      2.9 microgram/ml, 1.03 +/- 0.12 microgram/ml) (P < 0.05). Serum secretory IgA
      levels in the common duct stones (26.53 +/- 1.75 microgram/ml) and malignant
      obstructive jaundice groups (26.03 +/- 3.48 microgram/ml) were significantly
      higher than the gallstone group (18.45 +/- 4.56 microgram/ml). The bile-to-serum
      concentration ratio of total IgA, secretory IgA, and free secretory component
      levels rose significantly within 48 hours after relief of obstruction.
      CONCLUSIONS: Biliary obstruction secondary to both calculus or malignancy of the
      hepatobiliary system causes suppression of bile IgA secretion and elevated serum
      level of secretory IgA. Bile secretory IgA secretion recovers with endoscopic
      drainage of the obstructed system.

PMID- 8566636
TI  - Complete disruption of the main pancreatic duct: endoscopic management.
AB  - BACKGROUND: Complete disruption of the main pancreatic duct is an unusual event
      in the course of acute or chronic pancreatitis. Endoscopic management has already
      proven effective in the treatment of partial ruptures. METHODS: Thirteen patients
      presented over a 7-year period with acute (9 patients) or chronic (4 patients)
      pancreatitis complicated by complete disruption of the main pancreatic duct and
      cyst formation. Endoscopic treatment was attempted in 12. Treatment varied
      depending on the site of the rupture and accessibility of the pseudocyst and
      consisted either of transpapillary drainage (3), cystogastrostomy (3),
      cystoduodenostomy (2), or combined procedures (4) when one of these procedures
      did not induce significant decrease in collection size. Long-term results were
      obtained by observing the patients with ultrasound, CT, ERCP, and clinical
      evaluation. RESULTS: Short-term results were excellent with complete cyst
      resolution and clinical recovery in all but one patient treated by endoscopy. Two
      patients had pseudocyst infection successfully treated by drainage and
      antibiotics. Long-term follow-up was available for 11 patients (mean duration,
      30.2 months; range, 12 to 72 months) without relapsing clinical symptoms or
      pseudocyst. CONCLUSIONS: Endoscopic management is effective and safe for treating
      patients with complete main pancreatic duct disruption. A double drainage
      combining transpapillary drainage and cystoenterostomy must be done in selected
      instances, especially when rupture occurs in the setting of chronic pancreatitis
      with stricture or stone distal to the rupture.

PMID- 8566637
TI  - Endoscopic stenting for pain relief in chronic pancreatitis: results of a
      standardized protocol.
AB  - BACKGROUND: Pancreatic endoscopic stenting aims to relieve abdominal pain due to
      chronic pancreatitis. Optimal treatment modalities and post-treatment effects
      have still to be determined. The object of this study was to investigate the
      results of a standardized protocol of endoscopic stenting. METHODS: Twenty-three
      patients with abdominal pain due to chronic pancreatitis and stricture of the
      distal main pancreatic duct were treated according to the following protocol:
      after balloon dilation of the stenosis, a 10F stent was placed into the main
      pancreatic duct and then exchanged every 2 months, the total duration of drainage
      being 6 months. RESULTS: Use of analgesics could be discontinued in 17 patients
      (74%) on termination of drainage, and in 12 patients (52%) 1 year later. These
      results were significantly associated with reduction of main pancreatic duct
      diameter and resolution of stricture, but were not influenced by abstinence from
      alcohol and pancreatic enzyme supplementation. CONCLUSIONS: Pancreatic duct
      stenting results in short-term clinical improvement in patients with chronic
      pancreatitis and proximal main pancreatic duct stricture. Persistence of
      advantageous clinical results is to be expected in 50% of cases and when
      strictures have resolved.

PMID- 8566638
TI  - A placebo-controlled trial using intravenous atropine as an adjunct to conscious
      sedation in pediatric esophagogastroduodenoscopy.
AB  - BACKGROUND: The usefulness of intravenous atropine as an adjunct to conscious
      sedation in pediatric esophagogastroduodenoscopy remains an unresolved issue.
      METHODS: This prospective, double-blind, randomized study examined 101 patients,
      who were randomized to receive either intravenous atropine 0.02 mg/kg (maximum
      0.4 mg) or a placebo of normal saline solution prior to the procedure. RESULTS:
      The mean maximum heart rate during the procedure and the percentage of time that
      the heart rate was more than 1 standard deviation above mean for age was
      significantly greater in the atropine group as compared to the placebo group (p <
      0.0005). There was no significant difference between groups in the amount of
      secretions noted, gastric motility, retching or vomiting, facial flushing, or
      dysphoria. There were no causes of significant bradycardia or hypotension in
      either group. There was a significant number of patients greater than 5 years of
      age and receiving meperidine and atropine (as compared with meperidine and
      placebo) whose arterial oxygen saturation dropped below 90% during the procedure
      (p = 0.0485). CONCLUSIONS: We found that the use of atropine when used as an
      adjunct to conscious sedation in children undergoing upper endoscopy did not
      increase the safety of the procedure or provide significant benefits. We do not
      recommend the routine use of atropine for upper endoscopy in pediatric patients.

PMID- 8566639
TI  - Long-term results of pancreatic stents in chronic pancreatitis.
AB  - BACKGROUND: Pancreatic stenting is a new nonsurgical treatment for patients with
      chronic pancreatitis and pain. We studied the long-term safety and efficacy of
      pancreatic stenting. METHODS: Between 1982 and 1993, 51 patients with chronic
      pancreatitis and persistent pain with dominant strictures in the pancreatic duct
      were treated with plastic pancreatic stents. RESULTS: Stent insertion was
      successful in 49 of 51 patients. Early complications occurred in 9 of the 51
      patients (18%). Patients were followed for a median of 34 months (range 6 to
      128). Nine of the 49 patients (82%) had clinical improvement. Sixteen of these 40
      patients still had their stents in place. Stents were removed in 22 of the 40
      patients with persistent beneficial response in all (median follow-up 28.5
      months). The long-term effect of stenting could not be evaluated in the remaining
      2 patients because they had a double bypass operation. Stent dysfunction occurred
      in 27 of the 49 patients (55%) and was successfully treated by exchanging the
      stent. CONCLUSIONS: Pancreatic stenting was associated with minimal early
      complications, but stent dysfunction remained a frequent late complication.
      Pancreatic drainage resulted in clinical improvement in 40 of the 49 patients
      (82%). Twenty-two of these 40 patients maintained the beneficial response after
      stent removal (28.5 months).

PMID- 8566640
TI  - Endoscopic balloon sphincteroplasty (papillary dilation) for bile duct stones:
      efficacy, safety, and follow-up in 100 patients.
AB  - BACKGROUND: Because sphincterotomy accounts for a major portion of the morbidity
      and mortality associated with ERCP, we have proposed endoscopic balloon papillary
      dilation or sphincteroplasty as an alternative. METHODS: We report the outcome in
      a series of 100 patients in whom balloon sphincteroplasty was attempted for bile
      duct stones up to 20 mm in diameter, with a median follow-up of 16 months (range
      6 to 30). RESULTS: During one ERCP session using sphincteroplasty alone, the bile
      duct was cleared in 78%, mechanical lithotripsy being required in 10% for stones
      greater than 12 mm in diameter. Incomplete duct clearance was achieved in a
      further 4%, all of whom underwent repeat ERCP with successful duct clearance
      without recourse to sphincterotomy. Failure to clear the bile duct with
      sphincteroplasty in the remaining 18% was primarily related to large stone size (
      > 15 mm). Sphincterotomy was required to clear the duct in 7%. Another 6%
      comprised elderly high-risk patients with multiple large stones greater than 15
      mm who were treated by stent insertion plus ursodeoxycholic acid. No papillary
      hemorrhage was observed; uncomplicated pancreatitis occurred in 5%. During a
      median follow-up of 16 months, 2% had recurrent symptomatic bile duct stones
      considered to have been unrecognized following the initial ERCP: these were
      removed after repeat sphincteroplasty. No clinical evidence of papillary stenosis
      was observed during follow-up. CONCLUSIONS: Endoscopic balloon papillary dilation
      or sphincteroplasty is a safe and effective alternative to sphincterotomy in the
      management of bile duct stones less than 12 mm; larger stones may require
      mechanical lithotripsy to facilitate duct clearance.

PMID- 8566641
TI  - Endoscopic aspiration mucosectomy as curative endoscopic surgery; analysis of 24
      cases of early gastric cancer.

PMID- 8566642
TI  - Clinical usefulness of a new miniscope in the diagnosis of pancreatic disease.

PMID- 8566643
TI  - Complete and partial agenesis of the dorsal pancreas within one family.

PMID- 8566644
TI  - Laparoscopic appendicectomy in the management of acute lower gastrointestinal
      bleeding.

PMID- 8566645
TI  - Physician or technician?

PMID- 8566646
TI  - Angiodysplasia and aortic valve disease: let's close the book on this
      association.

PMID- 8566647
TI  - Reports of obstructive jaundice with pancreatic carcinoma and a normal
      pancreatogram.

PMID- 8566648
TI  - A sphincterotome with variable-length wire.

PMID- 8566649
TI  - Passing a Crosby capsule into the duodenum using a duodenoscope.

PMID- 8566650
TI  - Natural history and prognosis of diarrhea of unknown cause in patients with
      acquired immunodeficiency syndrome (AIDS).

PMID- 8566651
TI  - The use of long-acting somatostatin analogue (octreotide) for prophylaxis of
      acute pancreatitis after endoscopic sphincterotomy.

PMID- 8566652
TI  - [Regulating effect of the hematopoiesis-inducing microenvironment on
      hematopoietic processes as affected by cytostatic drugs].
AB  - The study of bone marrow hemopoiesis, the count of hemopoietic precursor cells,
      bone marrow structural and functional organization, the level of humoral
      stimulators and secretion by hemopoiesis-inducing microenvironment (HIM) cells
      following a single injection of 5-fluorouracil, cyclophosphamide or adriamycin
      has found out that cytostatic-related changes in hemopoiesis recovery depend
      primarily on relationships between proliferation and differentiation of
      hemopoietic cells. These relationships are dictated by the state of HIM cells.
      Enhanced functional activity of HIM elements in response to hemopoietic tissue
      damage caused by adriamycin or cyclophosphamide promotes rapid hemopoiesis
      regeneration. At the same time, 5-fluorouracil gave rise to prolonged bone marrow
      hypoplasia, severe disorder of microenvironment cell function.

PMID- 8566653
TI  - [Specificity of antibodies formed in people with Rh-negative blood in response to
      administration to antigens C(rh', Rh2) and Cw(rhwf, Rh8)].
AB  - Anti-C, -Ce, -CD sera and monoclonal anti-C-antibodies with red cells varying by
      Rh-phenotypes comprising antigen C(w) have been studied. Four Rh-negative
      volunteer donors were reimmunized with antigens C and C(w). As shown by reactions
      of anti-C-sera, monoclonal antibodies anti-C with C(w)-positive cells, results of
      immunisation of the Rh-negative donors with antigen C(w) of Rh system, red cels
      containing Rh antigen C(w) contain also factor rh(C).

PMID- 8566654
TI  - [Morphology of apoptosis in normal and pathologic hematopoiesis].

PMID- 8566655
TI  - [Development of the hematopoietic system in the human fetus].

PMID- 8566656
TI  - [Megakaryocytopoiesis].

PMID- 8566657
TI  - [Effect of preliminary chronic low-dose gamma-irradiation on the compensatory
      potentialities of the hematopoietic system].
AB  - Rat experiments indicate that chronic gamma-preirradiation in a dose of 90.0 rads
      (dose rate 3.0 rad/day) inhibits development of adaptive reactions of
      hematopoietic system throughout resistance of general adaptation syndrome in
      emotional stress.

PMID- 8566658
TI  - [Clinical importance of tumor necrosis factor].

PMID- 8566660
TI  - [Analysis of the composition of therapeutic preparations of immunoglobulin and
      albumin using chromatography on biochrome H-70].

PMID- 8566659
TI  - [Use of monoclonal antibodies to lipopolysaccharide with the purpose of
      correction of cytokine activity in endotoxic shock in an acute experiment].

PMID- 8566661
TI  - [Diagnostic value of soybean reagent for determination of activated partial
      thromboplastin time].

PMID- 8566662
TI  - [Cryopreservation of platelets and their functional integrity].

PMID- 8566664
TI  - [Role of the amygdaloid complex of the brain in the regulation of blood
      coagulation].
AB  - The response of biochemical parameters of coagulation to chemical stimulation of
      different amygdaloid structures has been studied. It is demonstrated that a
      microinjection of L-glutamate, a stimulating amino acid, into the above
      structures induces hypercoagulation. This gives evidence for a direct implication
      of the amygdala, an essential structure of the limbic system, in the mechanisms
      controlling central regulation of blood coagulation with probable involvement of
      direct amygdalospinal tracts.

PMID- 8566663
TI  - [Debatable, self-evident, contradictory and unresolved questions in
      contraindications to giving blood].

PMID- 8566665
TI  - [The role of platelets in the protective effect of a combination of vitamins A,
      E, C and P in thrombinemia].
AB  - White rat experiments have shown that combination of vitamins A, E, C and P
      diminishes thrombin-induced thrombocytopenia and low platelet aggregation. This
      is explained by limited activation of free radical processes initiated by
      thrombin in plasma, red cells and platelets. It was found that thrombin ability
      to activate lipid peroxidation is not related to coagulatory transformation of
      fibrinogen, but is rather due to a direct contact of the enzyme with platelets. A
      protective effect of vitamins-antioxidants in thrombinemia is likely to rest on
      their ability to restrict activation of free radical oxidation in platelets.

PMID- 8566666
TI  - [Metabolic markers of chronic liver disease].
AB  - The association between chronic liver disease and plasmatic lipids and glucidic
      metabolism was studied. The liver was evaluated with biochemical variables,
      ultrasound and upper gastrointestinal endoscopy. 12 chronic liver diseases
      patients and 10 normal were studied. 83.3% of patients showed lipidic
      abnormalities, 66.6% on the cholesterol levels and 41.7%, reduced HDL. When
      patients received 100 gr of glucose the response was abnormal in 83.3%. These
      results were compared with other "liver function test". 75% had abnormal
      bilirubin, 58.3% abnormal albumin, prothrombin time 58.3%, aminotransferases 75%.
      Esophageal verices were found in 75% of cases and ultrasound abnormalities in
      91.6% (27.3% cirrhosis, 54.4% diffuse abnormal patter and 18.2% splenomegaly).
      These findings show that lipidic and glucidic metabolism, and ultrasound, in
      chronic liver diseases are the more frequent abnormalities.

PMID- 8566667
TI  - [Postgraduate internship].

PMID- 8566668
TI  - [Treatment of esophageal stenosis with Savary-Gilliard balloons in children].
AB  - 30 patients (less than 15 years old) were admitted for esophageal strictures, 16
      of them secondary to corrosive injury. All the patients were treated with
      endoscopic dilation with Savary Gilliard bougie. The dilatation were done with
      general anesthesia using an Olympus GIF-XP10 endoscope and with fluoroscopic
      control. In the esophageal stenosis secondary to caustic ingestion endoscopic
      injection with Betamethasone was also used. The most frequent site of the
      stenosis was the upper third of the esophagus, and the main type of stenosis was
      tubular in the secondary to caustic burns and annular in the other group. In the
      posteaustic group 385 dilatations were performed in 115 sessions. Two
      perforations and one sepsis were reported in patients with corrosive stenosis.
      There was no mortality. 43.7% of the patients with corrosive stenosis and 85.7%
      with stenosis secondary to other causes obtained complete healing. Oesophageal
      dilatation with Savary-Gilliary bougies represents a safe and reliable method for
      the treatment of esophageal strictures.

PMID- 8566669
TI  - Isolation and axenization of two entamoeba histolytica strains.
AB  - We describe the isolation and axenization of two E. histolytica strains, obtained
      from the stools of two patients with the clinical diagnosis of dysentery. We used
      Pavlova's medium for initial polixenic culture, and TYI-S-33 (Diamond's) medium
      for monoxenic and axenic cultures. In order to eliminate the microorganism
      contaminating the stools the following antibiotics were used: penicillin,
      streptomycin, ampicillin, chloramphenicol, kanamycin, nistatin, ceftriaxone and
      amphoterycin B. Both strains grew in similar culture conditions with a yield of 2
      x 10(6) microorganism per tube of 15 ml. Both strains belong to pathogenic
      zymodemes, and virulence was determined by the capacity for producing hepatic
      abscesses in 100% of the hamsters inoculated intrahepatically.

PMID- 8566670
TI  - [Hematological values in exclusively breastfed infants during the 1st six months
      of life].
AB  - The maternal suckling is very important in the alimentation of the children and
      his effect in the hematopoietic system is not clear. Were studied the hematology
      children between three and six month, in the external consultation of Hospital
      Universitario Dr. Angel Larralde, since July 1990 to November 1992. 50 patients
      received exclusive maternal suckling and 10 artificial. The age and the sex in
      the three groups were homogeneous. The values of hemoglobin was greater in the
      exclusive maternal suckling group, with a 72% of the patient with values between
      10.2 and 11.9 gr. Was not significative difference in the account leucocyte. The
      polymorphonuclear percentage was less in the exclusive maternal suckling group
      with values between 20 and 34% in the 84% of the cases. The lymphocyte account
      was greater in this same group, with the 92% of the patients with values between
      60 and 74%. We conclude that the different king of suckling affect in important
      form the hematology values in the first six month of the live.

PMID- 8566671
TI  - [Immunological detection of aflatoxin-albumin adducts in children with chronic
      hepatitis B infection].
AB  - The value of aflatoxins is well known as a carcinogenic, mutagenic and
      teratogenic, likewise its association with the hepatitis B virus. In addition, it
      is known the incidence of hepatocellular carcinoma in such viral infection. A
      study was performed on the albumin adducts-aflatoxins levels in sera determined
      by ELISA method of children within 3-15 years old at the Service of Pediatric
      Gastroenterology from the National Institute of Gastroenterology. Samples
      consisted of 40 patients with chronic active hepatitis (CAH) B, 10 HBsAg+
      carriers and 20 controls. The CAH group, showed a 32.5% of positiveness with a
      maximum levels of 25pg aflatoxin lysine/mg albumin while 20% of HBsAg positive
      carriers showed levels of un 12.3 pg aflatoxin lysine/mg albumin and 15% of the
      control group 5pg AF lysine/mg albumin. It can be observed that aflatoxin levels
      in patients of CAH presented values up to 5 times over the control group. This
      study suggest the validity of aflatoxin-albumin adducts as a marker of chronic
      exposure to this carcinogen and its importance in relation with the virus of
      hepatitis B.

PMID- 8566672
TI  - [Effects of cholestasis on hepatotoxicity of acetaminophen in rats].
AB  - Acetaminophen high doses toxicity has been reported in clinical and experimental
      studies in relation with cytochrome P-450. (Acetaminophen metabolite). Thinking
      that biliary tract obstructions hould increases drugs toxicity because interferes
      toxic substances excretion or it modify the activity of P-450 we decided to study
      acetaminophen toxicity in rats with biliary tract obstruction. Male sprague
      Dawley rats were used (body weight 250-400 gr) in two groups: Group I control (6
      rats) with choledoco bile duct ligated; two doses of saline solution 0.9%
      Intraperitoneal, 0.2 ml/100 gr. were administrated. Group II (Same surgical
      intervention) received two doses of acetaminophen (intraperitoneal) solution (400
      mg/Kg). This group was divided in two (6 rats each), one of this was sacrificed
      at 48 h. and the other one at 120 h. after acetaminophen injection. Total, direct
      and indirect bilirubin, alkaline phosphatase, ALT and AST transaminases,
      hematology study, liver weight, histological studies of liver and kidney were
      performed in all rats. High incidence of liver necrosis ans significative
      transaminases increases were found in group II. Our results were discussed taking
      account that recent biliary tract obstruction increase acetaminophen toxicity, at
      a half doses reported in other studies. It is possible that mixed oxidation
      system activity of cytochrome P-450 was increased in our research.

PMID- 8566673
TI  - [Changes in the natural history of peptic ulcer after Helicobacter pylori
      eradication. Randomized, double-blind, placebo controlled trial. Follow-up of 44
      months].
AB  - We included 63 patients (p) with duodenal ulcer and Helicobacter pylori infection
      to be treated with Famotidine 40mg/day for six weeks. In the first ten days one
      group of 33p (TG) received Metronidazole 250mg plus Amoxicillin 500mg T.I.D and
      30p (PG) placebo. Helicobacter pylori was eradicated in 62.5% of TG. Infection
      was always associated with ulcer recurrence. Healing was similar in both groups
      but recurrence was statistically significant after three month in PG and in the
      first year all Pg had relapsed. At 44 month only 25% of TG relapsed. The natural
      history of peptic ulcer disease was changed with Helicobacter pylori eradication.

PMID- 8566674
TI  - [Inflammatory response associated with Helicobacter pylori infection in gastric
      mucosa with intestinal metaplasia in a population in high risk for gastric
      cancer].
AB  - Intestinal Metaplasia (IM) and Helicobacter Pylori (HP) infection had been
      related to gastric carcinogenesis. With the intention to know the relationship
      among HP infection, IM and inflammatory response of the mucosa in an area of high
      prevalence of gastric cancer, we studied 800 persons that attended the Gastric
      Cancer Mass Survey, ongoing in the State Tachira, Venezuela, since 1981. Out of
      these subjects, 259 had histology diagnosis of IM (32.4%) 52.1% were IM type Y,
      19.3% type II and 22.8% type III (sulfomucin secretory). Histology demonstrated
      with Giemsa stain HP in 94.6% of the cases. Association between HP and
      inflammation response in gastric mucosa with IM, was statistically significant (p
      = 0.001). The are heavier bacteria overload in IM type I than in type III
      although it is not statistically significant. We ponder if gastric mucosa
      inflammation due to HP, conditions development of IM as a hostile way of the
      gastric environment to restrain bacterial growth. This phenomenon ally with other
      oncogeneous factors could induce to premalignant lesions and eventually gastric
      cancer.

PMID- 8566675
TI  - [Critical evaluation of a decade experience with early gastric cancer].
AB  - The evaluation of early gastric cancer in the Central Hospital of IVSS "Miguel
      Perez Carreno" of the urban area shows a detectability rate of 5.03% from gastric
      carcinoma total cases. Depressed macroscopic type and differentiate microscopic
      type are the most frequent. Predominant location is antrum. Early Gastric Cancer
      with elevated component, differentiate papillar type, submucosal invasion and
      with positive lymph node must be operated with very carefully and systematic
      lymph node dissection, depending on the location and the size of the primary
      tumor, and also post-operative adjuvant chemotherapy is likely to be necessary as
      well, to achieve diminishing the recurrence and mortality rates. Its our duty
      look for a better team work and methodology in the detection of early gastric
      cancer to obtain more superficial and smaller lesions. So there fore another
      therapeutical alternatives such as Endoscopical Mucosal Resection and
      Laparoscopic Wedge Resection could take a place in the future.

PMID- 8566676
TI  - [Use of glucomannan dietary fiber in changes in intestinal habit].
AB  - It has been proven that fiber is effective in the treatment of multiple
      nosological entities, specially of the colonic pathology. In the present study,
      two dose of Glucomannan (3 gr/day and 4 gr/day) were evaluated within the
      modification of the intestinal habit and stool characteristics. 60 patients were
      included in a random, parallel, double blind, cross over trial study versus
      placebo. The modification of the intestinal habit was evaluated through
      variations of daily and weekly evacuations, appraising the stool's consistency
      and size, satiety after meals tiresomeness between meals, constipation, diarrhea
      and flatulence. An increase in the number of daily and weekly evacuations during
      the Glucomannan vs placebo treatment was appreciated and, between the two dose of
      Glucomannan, a difference was observed as to the large the dose, the large the
      number of daily and weekly evacuations. Evacuations during the phase of
      Glucomannan 3 gr/day increased 0.5 times per day, 3 more per week above baseline
      values. On the 4 gr/day treatment of Glucomannan evacuations increased 0.9 times
      per day, 6 more per week above baseline values. Patient during the placebo period
      presented no statistically significant different. No difference was appreciated
      as to post-meal satiety, nor tiresomeness between meals, possibly due to
      treatment periods being 5 weeks long. No larger number of cases with diarrhea or
      flatulence were appreciated with the use of Glucomannan. Glucomannan proved to be
      superior to placebo, and the 3 gr/day and 4 gr/day doses turned out to beneficial
      in the improvement of the assessed parameters--better results were obtained using
      4 gr/day of Glucomannan than 3 gr/day.

PMID- 8566677
TI  - [Persistent diarrhea].
AB  - In this article the current concepts on persistent diarrhoea are reviewed.
      Persistent diarrhoea is important because its aetiology is unclear, is difficult
      to treat, affects the nutritional status and increases the risk of death. The
      identification of risk factors for persistent diarrhoea is important because it
      can obtain valuable information relative to the pathogenesis and prevention of
      this disease. The concepts of diarrhoea and risk factors are also reviewed. In
      addition we explore the methods of management and treatment of patients with
      persistent diarrhoea.

PMID- 8566678
TI  - [Liver autoimmune diseases. II. Primary biliary cirrhosis].

PMID- 8566679
TI  - [Cholangiocarcinoma].
AB  - The cholangiocarcinoma is a low-prevalence neoplasia, but represents a great
      medical challenge in its diagnosis and treatment because of its insidious
      clinical manifestations. Its cellular origin has been associated to other hepatic
      tumors, and to multiple congenital or acquired factors (infections, drugs and
      other diseases). The most frequent histological type is the adenocarcinoma and
      the most common localization is the choledochal duct; local metastases are
      frequently found in autopsies. The usual clinical findings are pruritus, weight
      loss, anorexia, jaundice and hepatomegaly. The immunohistochemical advances
      related to oncogenes (ras & C-erb B-1) and tumor markers (Epidermal Growth Factor
      and Integrin among others) allow to make differential diagnosis with other
      hepatic cancers and will provide valuable information about its cell biology. The
      initial approach to patients with this disease is made by ultrasound (US), which
      can be associate to Doppler; Computed Axial Tomography and Nuclear Magnetic
      Resonance have similar sensitivity and specificity, so they are preferred to US
      in the elderly with history of weight loss. It's better to perform Percutaneous
      Transhepatic Cholangiography than Endoscopic Retrogrado Pancreatocholangiography
      when its possible because the first permits a comprehensive visualization of the
      biliary tree. The treatment includes resection and endoprosthesis placement. The
      combination of surgery, Chemotherapy and Radiotherapy allows to achieve the best
      survival rates, and opens a door to new strategies related to this malignancy.

PMID- 8566680
TI  - [Transrectal ultrasonography in the preoperative staging of rectal
      adenocarcinoma. Cross-sectional study 1991-1994].
AB  - Preoperative evaluation of the depth of invasion in the rectal wall as well as
      the presence of regional metastatic nodes are considered important factors in
      order to decide surgical treatment as well as prognosis in cases of cancer of the
      rectum. This investigation was carried out in order to establish how usefull
      transrectal ultrasound was for the pre-operative evaluation of cancer of the
      rectum. We studied 78 patients with different ano rectal pathology, among them 40
      patients with confirmed ADC of the rectum that were completely studied and had
      ultra sonographic as well as surgical and pathological staging using TNM
      classification. Confiability indicators of transrectal ultrasound when compared
      with pathology findings, showed a sensibility of 100% in T1-T2 and T4; in T3
      lesions sensibility was 76%. Specificity was between 94% and 100% in all stages.
      We believe that trans-rectal ultrasound is a usefull, precise and reliable
      diagnostic tool, for staging purposes of rectal carcinoma.

PMID- 8566681
TI  - [Helicobacter pylori eradication heals the duodenal ulcer. Randomized, simple,
      and controlled study with omeprazole].
AB  - 60 patients with Helicobacter pylori (Hp) infection and duodenal ulcer (DU) were
      randomized to received either: I) Two weeks of bismuth subcitrate, metronidazole
      and amoxicillin (TG) or II) Omeprazole for four weeks (OG). Endoscopy and antral
      biopsies were done at entry and four weeks after treatment, control endoscopy was
      performed 2-4-8 and 12 weeks after inclusion in the trial. Healing was similar in
      both groups at two four weeks. At twelve weeks DU recurred in OG 65% vs 13.36% in
      TG and Hp infection was present. Our results showed that Hp eradication healed DU
      in a similar rate than Omeprazole providing further evidence of a causal link
      between Hp infection and duodenal ulcer.

PMID- 8566682
TI  - [Influence of colloidal bismuth subcitrate, metronidazole, and amoxycillin on
      Helicobacter pylori and gastroduodenal ulcer healing].
AB  - In many works performed in different countries, including Cuba, the microorganism
      Helicobacter pylori (Hp) is involved in the etiopathogenesis and relapse of
      gastroduodenal ulcer (GDU). In a previous work, we saw that under treatment of
      Colloidal bismuth subcitrate (CBS) or Metronidazole (M) alone during 4 weeks, the
      percentage of Hp clearance obtained was very low. So, we decided to extend the
      treatment with a unique drug up to 6 weeks or to make a combination of drugs
      during 4 weeks. 114 patients with GDU endoscopic diagnosis and Hp positive by
      urease test antral biopsy were located in 5 schedules of treatment: 1) CBS 480 mg
      daily during 6 weeks; 2)M 1 g daily during 6 weeks; 3) CBS 480 mg daily plus M
      750 mg daily during 4 weeks; 4) CBS 480 mg daily plus Amoxycillin (A) 1500 mg
      daily during 4 weeks and 5) M 750 mg daily plus Amoxycillin 1500 daily during 4
      weeks. Endoscopy and urease test were repeated at the end of treatment. Healing
      of ulcer was obtained in 83.3%; 36.4%; 89.2%; 91.9% and 54.6% respectively. Hp
      clearance was reached in 55.6%; 27.3%; 67.6%; 70.3% and 27.3% respectively. So,
      the schedules of treatment less effective (concerning both healing and Hp
      clearance) were M during 6 weeks and M plus A during 4 weeks. It has been
      reported that Hp strains may become resistant to nitroimidazolics in the course
      of treatment and that this resistance could be diminished by the coadministration
      of CBS. We recommend in GDU-Hp positive a treatment with CBS during 6 weeks or
      the combination of CBS, which action is basically local, with an antibiotic such
      as M (no more than two weeks) or Amoxycillin during 4 weeks.

PMID- 8566683
TI  - [Evaluation of the acceptability of a formula for children with diarrhea in a
      marginal community].
AB  - Evaluated the acceptability of a nutrition formula consisting of pumpkin-rice
      chicken and oils; in a marginal community to children between the ages of 7
      months to 5 years old when acute diarrhea was present. The acceptability was also
      evaluated in the mothers, who indicated that they liked food very little.
      Nevertheless, they admitted that they would give the product to their children.
      During the period of study 26 cases of diarrhea were reported of the 26 children,
      6 children consumed all the food offered, 16 children showed variable acceptance
      and only 4 children reject the food completely. By age-groups, the acceptability
      was 75.69% for children between the ages of 7 months to one year. 72.90%
      acceptability for ages between 13 months to 2 years and 78.28% for ages between
      25 months to 5 years old. The total acceptability was 75.66%. All cases presented
      marked decreased in diarrhea and an increased in the consistency of the feces
      with the third dose.

PMID- 8566684
TI  - [Prevalence of antibodies against hepatitis C virus in multitransfused patients].
AB  - We have done a study in order two know the prevalence of anti-hepatitis C virus
      antibodies in polytransfused patients with hemophilia, leukemia and hemolytic
      anemia, along with 17 healthy donors, without previous history of transfusions.
      We analyzed samples from 10 hemophilic patients and 12 from leukemia, lymphoma
      and hemolytic anemia, all of them had received blood or blood products, at least
      six months before the study. Using a second generation ELISA, 4 positive sample
      (3 hemophilic and 1 lymphoma) were detected (10.26%), which represent a
      prevalence of 30% in the hemophilic group, in contrast with the prevalence
      detected in other countries. A very significant statistic association was
      demonstrated, between the positive ELISA, the amount of the transfused product (P
      < 0.0004) and the type of blood product used for transfusion (crioprecipited, P =
      0.000, plasma P = 0.000).

PMID- 8566685
TI  - [Pathology of the cecal appendix in our country. An analysis of 936 surgical
      specimens of appendectomy].
AB  - Analysis was made of 436 specimens of appendectomy in the Caracas University
      Hospital during the year 1.990. Ages of the patients ranged between 9 months and
      79 years (average age: 21 years). 236 were males and 200 females. The pathology
      found most frequently was the acute inflammatory processes, followed by secondary
      reactive changes to other entities, many of which were unspecified (e.g. pelvic
      inflammatory disease) and other specific (such as infestation by parasites) less
      frequently were found tumoral processes such as mucocele, carcinoid tumor and
      those which involved another portion of the digestive apparatus and which
      secondarily affect the appendix.

PMID- 8566686
TI  - [Use of the Clotest and Pyloriset in the identification of Helicobacter pylori in
      asymptomatic healthy adults].
AB  - The Helicobacter Pylori (Hp) has been related with the pathogenesis of the
      chronic gastritis, peptic ulcer, non ulcerous dyspepsia, and in the last studies
      it has been found in a great prevailing way in populations with gastric cancer
      risks. The purpose of this study was to determine the presence of Hp in
      asymptomatic adults, volunteers, healthy, by means of the utilization of two
      diacritic tests, a serologic test for the determination of antibody IgG anti Hp
      (Pyloriset) and the tests Urease (Clotest) relating it with the development of
      lesions. We studied 20 persons, from whom we took peripheral blood samples for
      the determination of Hp by means of the agglutination test of latex (Pyloriset)
      and a superior digestive endoscopy was carried out (SDE) with a gastric biopsy
      for the Tests of Ureasa (Clotest). In 15 adults (75%) the clotest was positive
      and in 13 persons (65%) the pyloriset was positive. In 9 persons (47%) the Hp was
      evidence by both methods. In 13 (65%) the SDE was pathological concluded and all
      were positive for the Hp. In 7 (35%) the SDE resulted normal. The presence of the
      antibody against the, Hp predicts alterations of the gastric mucosa like the
      development of the chronic gastritis, peptic ulcer and other pathologies. The
      Clotest is a simple tests, quick and sensible that allows us to apply immediate
      treatment. Our results suggest a high incidence of this bacteria in our workers,
      which justifies high prospective studies to determine same.

PMID- 8566687
TI  - [Biliary cystadenoma. Report of a case].
AB  - Biliary Cystadenoma are rare benign neoplasms that occurs mainly in young women.
      Clinical features includes abdominal pain and biliary obstruction. The diagnosis
      is for clinical features and radiologic method, but require the pathological
      report. The treatment is surgical. We report a 30 years old woman, with biliary
      obstruction and radiological findings of a neoplasm located in the left hepatic
      duct, that was surgically removed. The pathological report was a biliary
      cystadenoma. We discuss the clinical radiological and pathological tindings.

PMID- 8566688
TI  - [Accessory spleen: compensating hypertrophy after of splenectomy. A case report].
AB  - The prevalence of accessory spleens has been reported to be about 7.1% in
      infants. When these patients undergo splenectomy without removal of the accessory
      spleen, the latter develop hypertrophy later in life and can reach the size of a
      normal spleen, with clinical manifestations similar to the ones before surgery.
      We report the case, of fourteen-old boy, who had splenectomy 7 year ago, for
      refractory and recurrent thrombocytopenia, who had splenectomy at age 7 years
      because of persistent thrombocytopaenia, resistant to non-surgical treatment, and
      who was found by conventional ultrasound study, doppler duplex color and
      selective angiography to have a hypertrophied spleen with sings of portal
      thrombosis and portal hypertension.

PMID- 8566689
TI  - [Trichobezoar: unusual diagnosis. Report of 3 cases].
AB  - We report 3 cases of gastric trichobezoar, recorded in the last 10 years in our
      Hospital. All the cases presented abdominal pain and tumor, as well as upper
      obstructive symptoms. The 3 cases were surgically treated with satisfactory
      evolution. The clinical has to consider this diagnosis taking into account the
      data summarized here. Surgery is a successful treatment for these cases. The
      literature on bezoars is reviewed.

PMID- 8566690
TI  - [Evaluation of tumor response through of morphometric measurements.
      Quantification of apoptosis].
AB  - The tumor response in solid neoplasias can be evaluated through volumetric
      measurements. The advance of the technology and the appearance of new therapeutic
      alternatives as: hyperthermia, immunotherapy, photodynamic therapy have
      originated discrepancy with the volumetric measurement of the tumor because the
      tumor mass can increase or remain in the same size but with tissue modification
      and increase of the inflammatory and necrotic reaction. There are also other
      types of morphometric measurement, for the evaluation of the amount of hypoxic
      cells in the tumor tissue through indirect methods that measure the metabolic
      level of the tumor tissue; one of this morphometric measurement quantitates
      apoptosis by light microscopy as tumor regression response. This technique could
      facilitate experimental studies because of the use of peripheral tumoral tissue
      obtained with thin needles directed through image equipment.

PMID- 8566691
TI  - [Is the treatment of chronic viral hepatitis C with interferon-alpha effective?].

PMID- 8566692
TI  - [Autoimmune diseases of the liver, III. Primary sclerosing cholangitis].

PMID- 8566693
TI  - [Carlos Chagas and Chagas disease].

PMID- 8566694
TI  - Heterologous expression of Escherichia coli porin genes in Salmonella typhi Ty2:
      regulation by medium osmolarity, temperature and oxygen availability.
AB  - Electrophoretic analysis of outer membrane proteins showed that Salmonella typhi
      OmpC expression is not reciprocally regulated relative to OmpF as described for
      Escherichia coli and S. typhimurium. When bacteria were grown in minimal media,
      both OmpC and OmpF were repressed as the osmolarity increased. However, in Luria
      broth, expression of OmpC was slightly induced by osmolarity up to 0.3 osmM.
      Plasmids bearing E. coli ompC-lacZ or ompF-lacZ gene fusions were studied for
      their expression in S. typhi and E. coli. Under anaerobic growth conditions,
      expression of ompC-lacZ in S. typhi was maximal at 0.16 osmM, while in E. coli
      expression was maximal at 0.7 osmM. ompF-lacZ expression was similarly repressed
      by medium osmolarity and anaerobiosis in both species. In contrast, a drastic
      difference in the regulation of OmpF by temperature was observed; at 37 degrees C
      ompF-lacZ expression was repressed in E. coli, while in S. typhi it was induced.

PMID- 8566695
TI  - Streptococcus pneumoniae type 3 encodes a protein highly similar to the human
      glutamate decarboxylase (GAD65).
AB  - A 2.5-kb ScaI fragment of the type 3 pneumococcal strain 406 DNA containing a
      1425-nucleotide open reading frame (gadA) and encoding a 475-amino acid protein
      (M(r) 54,427) was characterised. The gene gadA was expressed in Salmonella
      typhimurium. Pulsed-field gel electrophoresis and Southern blotting analysis of
      DNAs prepared from several pneumococcal serotypes showed that only those clinical
      isolates belonging to serotype 3 harbour the gadA gene. Sequence comparison of
      GadA with proteins included in the data banks revealed the highest similarity
      with human glutamate decarboxylase (GAD65) (59% similarity, 28% identity). Auto
      antibodies to GAD65 have been associated with the onset of insulin-dependent
      diabetes mellitus. Interestingly, several epitopes of GAD65 that have been
      identified as immunodominant are particularly well conserved in the pneumococcal
      GadA.

PMID- 8566696
TI  - Metabolic studies by 1H NMR of different forms of Trypanosoma cruzi as obtained
      by 'in vitro' culture.
AB  - By culturing Trypanosoma cruzi epimastigotes in modified Grace's medium with 10%
      foetal bovine serum, a significant quantity of metacyclic forms could be
      obtained. Transformation was observed after 8 days of culture, with metacyclic
      forms reaching 75%. Cultured Vero cells were infected with metacyclic forms and
      maintained until free-amastigote forms were obtained. Additionally, amastigote
      like forms could be obtained by subjecting metacyclic cultures to heat shock.
      Parasites were grown with glucose as the major carbon source. The metabolites
      produced and excreted during culture were identified by difference proton nuclear
      magnetic resonance spectroscopy and quantified by enzymatic methods. The final
      products of glucose catabolism differed not only quantitatively but also
      qualitatively for the three major life-cycle stages of T. cruzi. The end products
      of metabolism produced by epimastigote forms were mainly acetate and pyruvate
      and, to a lesser extend, L-alanine and ethanol. Differences between epimastigotes
      and metacyclic forms were only quantitative. However, free amastigotes as well as
      amastigote-like forms, excreted acetate, glycerol, and pyruvate and to a lesser
      extent succinate, but no L-alanine or ethanol.

PMID- 8566697
TI  - Identification of the replication region of Lactobacillus acidophilus plasmid
      pLA103.
AB  - The structure of the region necessary for replication of the plasmid pLA103 from
      Lactobacillus acidophilus TK8912 has been characterized. Sequence analysis
      revealed that the replication region contained an open reading frame (OrfA)
      encoding a 282-amino acid peptide preceded by a 22-bp tandem repeat sequence
      region. The predicted OrfA protein showed homology to the replication protein of
      a plasmid from Pediococcus halophilus. The plasmid containing the repeat sequence
      region preceding OrfA was able to replicate in the Lactobacillus host when
      provided with OrfA in trans, suggesting that the repeat sequence region contains
      the origin sequence essential for the pLA103 replication.

PMID- 8566698
TI  - Comparative analysis of gene sequences encoding ammonia monooxygenase of
      Nitrosospira sp. AHB1 and Nitrosolobus multiformis C-71.
AB  - DNA encoding ammonia monooxygenase from two phylogenetically related autotrophic
      nitrifying bacteria, Nitrosospira sp. AHB1 and Nitrosolobus multiformis C-71, was
      amplified by PCR. The resulting products were cloned into the vector pCR-Script.
      A continuous region of DNA of about 1.5 kb for strain AHB1 and 1.24 kb for N.
      multiformis C-71 was analysed. These comprised the major part of the gene amoA
      encoding the active site polypeptide and, directly downstream, the 5' portion of
      the amoB gene. The identity values for these sequences at the amino acid level
      were 93.0% for amoA and 96.1% for amoB. The corresponding values for the nucleic
      acid sequences were 86.7% and 88.8%, respectively. The identity of the 16S rRNA
      gene of strain AHB1 to that of N. multiformis C-71 was at least 98.5%. The
      different degree of sequence conservation between the 16S rDNA and the genes
      encoding for ammonia monooxygenase facilitates the application of the latter as a
      molecular tool for a fine-scale differentiation of autotrophic nitrifying
      bacteria, at the species or strain level, in both environmental and cultivation
      studies.

PMID- 8566699
TI  - Purification and characterization of the formate dehydrogenase from Desulfovibrio
      vulgaris Hildenborough.
AB  - Formate dehydrogenase from Desulfovibrio vulgaris Hildenborough, a sulfate
      reducing bacterium, has been isolated and characterized. The enzyme is composed
      of three subunits. A high molecular mass subunit (83,500 Da) is proposed to
      contain a molybdenum cofactor, a 27,000 Da subunit is found to be similar to the
      Fe-S subunit of the formate dehydrogenase from Escherichia coli and a low
      molecular mass subunit (14,000 Da) holds a c-type heme. The presence of heme c in
      formate dehydrogenase is reported for the first time and is correlated to the
      peculiar low oxidoreduction potential of the metabolism of these strictly
      anaerobic bacteria. In vitro measurements have shown that a monoheme cytochrome
      probably acts as a physiological partner of the enzyme in the periplasm.

PMID- 8566700
TI  - Aberrant gene for E1 Tor hemolysin from Vibrio cholerae non-O1, N037.
AB  - Vibrio cholerae non-O1 strain N037 produced a hemolysin (NO37-Hly) which was
      antigenically similar to E1 Tor hemolysin (E1 Tor-Hly) but different in molecular
      size, hemolytic activity, and glucose binding capacity. In the gene encoding NO37
      Hly, a 4-bp insertion into the structural gene for E1 Tor-Hly (hlyA) was found.
      The insertion in a shift of codon frames generating a new stop codon in the
      downstream region. NO37-Hly was a truncated product of E1 Tor-Hly sharing 90% of
      the N terminal region. This suggested that the 10% C-terminal region of E1 Tor
      Hly is needed for the maximal hemolytic activity and glucose binding capacity.

PMID- 8566701
TI  - Translation of RNAIII, the Staphylococcus aureus agr regulatory RNA molecule, can
      be activated by a 3'-end deletion.
AB  - RNAIII, an RNA molecule shown to encode delta-hemolysin and independently to
      regulate toxin synthesis in Staphylococcus aureus, is transcribed at the mid
      exponential phase of growth, while its target genes are activated 2 h later, at
      the post-exponential phase of growth. We show here that the translation of RNAIII
      to the 26-amino acid peptide delta-hemolysin is delayed by 1 h, and that this
      delay is abolished when the 3'-end of this molecule is deleted. We suggest that
      structural changes of RNAIII to a translatable form of the molecule precede its
      regulation of target gene expression.

PMID- 8566702
TI  - Phenotypic characterisation and genetic complementation of dimethylsulfoxide
      respiratory mutants of Rhodobacter sphaeroides and Rhodobacter capsulatus.
AB  - Two chlorate resistant mutants of Rhodobacter sphaeroides were isolated which
      were deficient in dimethylsulfoxide reductase activity. Immunoblotting
      experiments showed that the phenotype of these mutants and that of Rhodobacter
      capsulatus strain DK9, a mutant unable to reduce dimethylsulfoxide, was
      correlated with low or undetectable levels of the dimethylsulfoxide reductase
      apoprotein. All three mutants were complemented by a cosmid from a library of
      Rhodobacter sphaeroides genomic DNA. Further genetic complementation analysis
      revealed that functions required for restoration of dimethylsulfoxide reductase
      activity in the Rhodobacter sphaeroides mutants were encoded on an 9 kb EcoR1 DNA
      fragment derived from this cosmid. Expression of this 9 kb DNA fragment in
      Escherichia coli showed that it encoded the dimethylsulfoxide reductase
      structural gene of Rhodobacter sphaeroides.

PMID- 8566703
TI  - An agarose slide method to follow the fate of bacteria within digestive vacuoles
      of protozoa.
AB  - A method to follow the fate of ingested bacteria within digestive vacuoles of
      protozoa is presented. Tetrahymena pyriformis, previously fed with bacteria, is
      deposited onto glass microscope slides covered with a film of nutritive agarose.
      The protozoa lyse and the digestive vacuoles containing the bacteria stay
      undamaged and can be observed microscopically. After incubation, microcolonies
      reveal those vacuoles which contained living bacteria. The method can be used to
      study the survival ability of the ingested bacteria. It is a potentially valuable
      technique for studies on digestion efficacy, virulence ability, or escape
      mechanisms of bacteria from digestion.

PMID- 8566704
TI  - A recombinant tyrosine aminotransferase from Trypanosoma cruzi has both tyrosine
      aminotransferase and alanine aminotransferase activities.
AB  - Tyrosine aminotransferase purified from epimastigotes of Trypanosoma cruzi
      displays an additional activity of alanine aminotransferase, absent in all other
      tyrosine aminotransferases characterized so far. Since the parasite's genome
      contains a high number of copies of the tyrosine aminotransferase gene, we could
      not rule out the possibility that two very similar proteins, with changed
      specificity due to a few amino acid substitutions, might be responsible for the
      two activities. We have now expressed in Escherichia coli a recombinant tyrosine
      aminotransferase as a fusion protein with glutathione S-transferase. The purified
      fusion protein, intact or after thrombin cleavage, displays tyrosine
      aminotransferase and alanine aminotransferase activities with apparent Km values
      similar to those for the natural enzyme, thus proving that they belong to the
      same protein.

PMID- 8566705
TI  - The effects of co-cultivation with the acetogen Acetitomaculum ruminis on the
      fermentative metabolism of the rumen fungi Neocallimastix patriciarum and
      Neocallimastix sp. strain L2.
AB  - The effects of co-cultivation with the hydrogen-utilizing acetogenic bacterium
      Acetitomaculum ruminis on the fermentative activities of the rumen fungi
      Neocallimastix patriciarum or Neocallimastix sp. L2 were investigated. In both co
      cultures acetate production increased, making it the predominant fermentation
      product, as the accumulation of lactate, formate, ethanol, H2 and (in the case of
      Neocallimastix sp. L2) succinate all decreased. The effects of co-cultivation
      with Methanobrevibacter smithii were more pronounced. Decreased activities of
      lactate dehydrogenase, alcohol dehydrogenase and (in the case of Neocallimastix
      sp. L2) fumarate reductase accompanied the shift in fermentation product
      formation. The rate of glucose utilization and the fungal biomass yield were also
      increased in the co-culture.

PMID- 8566706
TI  - Analysis of S-layer proteins of Lactobacillus brevis.
AB  - The presence of S-layer proteins in Lactobacillus brevis was examined by SDS-PAGE
      analysis. Thirty six out of a total of 41 L. brevis strains possessed S-layer
      proteins of molecular masses ranging from 38 to 55 kDa. Western blot analysis
      using antisera raised against whole cells of S-layer protein-carrying strains
      demonstrated the heterogeneity of L. brevis S-layer proteins. No clear
      relationship was observed between the presence of S-layer proteins or their
      immunological characteristics and the physiological activity of L. brevis as a
      beer spoilage organism.

PMID- 8566707
TI  - A comparison of gene organization in the zwf region of the genomes of the
      cyanobacteria Synechococcus sp. PCC 7942 and Anabaena sp. PCC 7120.
AB  - The region of the genome encoding the glucose-6-phosphate dehydrogenase gene zwf
      was analysed in a unicellular cyanobacterium, Synechococcus sp. PCC 7942, and a
      filamentous, heterocystous cyanobacterium, Anabaena sp. PCC 7120. Comparison of
      cyanobacterial zwf sequences revealed the presence of two absolutely conserved
      cysteine residues which may be implicated in the light/dark control of enzyme
      activity. The presence in both strains of a gene fbp, encoding fructose-1,6
      bisphosphatase, upstream from zwf strongly suggests that the oxidative pentose
      phosphate pathway in these organisms may function to completely oxidize glucose 6
      phosphate to CO2. The amino acid sequence of fructose-1,6-bisphosphatase does not
      support the idea of its light activation by a thiol/disulfide exchange mechanism.
      In the case of Anabaena sp. PCC 7120, the tal gene, encoding transaldolase, lies
      between zwf and fbp.

PMID- 8566708
TI  - Construction and characterization of Bordetella pertussis RecA- mutants.
AB  - Antibiotic drug-resistance cassettes (DRCs) were used to insertionally inactivate
      the wild-type Bordetella pertussis recA gene cloned into a suicide vector. The
      mutant allele was mobilized by conjugal gene transfer from Escherichia coli
      strain SM10 into different genetic backgrounds of B. pertussis. Southern
      hybridization studies of one of these mutants showed that it contained a DRC
      integrated within a recA gene situated within a ClaI genomic DNA fragment.
      Selected mutants were assayed to quantify recombinational and DNA repair
      deficiencies. These mutants were shown to be highly sensitive to both chemically
      and physically induced DNA damage. Gene transfer studies of another RecA- mutant
      also indicated that it was defective in intergenic recombination. No difference
      in hemolytic activity or production of capsule was detected between the RecA-
      mutants and their corresponding wild-type strains. The results of this
      investigation corroborate previous studies with the cloned B. pertussis recA
      gene, and demonstrate that the expression of the B. pertussis recA gene in the
      original host promotes both DNA repair and recombination.

PMID- 8566709
TI  - Overexpression of extracellular sucrase (SacC) of Zymomonas mobilis in
      Escherichia coli.
AB  - The extracellular sucrase (SacC) gene of Zymomonas mobilis was overexpressed in
      Escherichia coli BL21 using the T7 polymerase expression system. A low cell
      density induction method was designed to have maximum expression, and the
      conditions (IPTG concentration, ampicillin addition) were optimised to
      overexpress to the level of more than 60% of the total cellular protein
      representing SacC protein.

PMID- 8566710
TI  - Cloning and nucleotide sequence of a gene upstream of the eaeA gene of
      enterohemorrhagic Escherichia coli O157:H7.
AB  - A DNA segment located immediately upstream of the eaeA gene of enterohemorrhagic
      Escherichia coli O157:H7 strain HA1 was cloned and sequenced. This segment
      contained an open reading frame encoding a predicted protein of 156 amino acids.
      A database search identified similar open reading frames upstream of the eaeA
      gene in two other bacterial pathogens, i.e. enteropathogenic E. coli and
      Citrobacter freundii. The predicted amino acid sequence of the enterohemorrhagic
      E. coli protein shared 96.8% and 94.2% identity with the enteropathogenic E. coli
      and C. freundii sequences, respectively. Because the open reading frame is
      located within the locus of enterocyte effacement region of the E. coli
      chromosome, a 'hot spot' for insertion of virulence factor genes, and shares high
      sequence homology with attaching and effacing EPEC and C. freundii, this protein
      may be associated with pathogenicity of E. coli O157:H7.

PMID- 8566711
TI  - Association of colony variation in Serratia marcescens with the differential
      expression of protease and type 1 fimbriae.
AB  - Several clinical isolates of Serratia marcescens were found to dissociate on
      peptone glycerol agar into colonies with red and pink or white and gray
      phenotypes that differ in the expression of proteolytic activity and mannose
      sensitive type of hemagglutination. Colonies of red and white type were
      proteolytically active but did not express hemagglutination, whereas pink and
      gray colonies were protease-deficient but agglutinated guinea pig erythrocytes.
      Site-directed mutagenesis of a red laboratory strain S. marcescens SM6 resulted
      in selection of protease negative derivative prt::G7 which expressed the pink
      phenotype with hemagglutinating activity. It is suggested that a DNA-regulatory
      element may be involved in this type of colony variation.

PMID- 8566712
TI  - The replicator region of the Rhizobium leguminosarum cryptic plasmid pRL8JI.
AB  - The replicator region of the cryptic plasmid pRL8JI from Rhizobium leguminosarum
      strain 3841 was cloned and sequenced. The recombinant plasmid (pYK3) was selected
      by function from a partial EcoRI library of total DNA cloned in pSUP202 and shows
      incompatibility with plasmid pRL8JI when conjugated into R. leguminosarum strains
      3841 and its derivative 1062. The cloned insert (approximately 10.5 kb) comprises
      five EcoRI fragments none of which confers replicative stability when cloned
      individually. A single 5.0-kb BamHI fragment, that spans all five EcoRI fragments
      and confers replicative stability on pSUP202 in R. leguminosarum, has been
      sequenced. This replicator region shows organisational and sequence similarity to
      the replicator regions of the Agrobacterium plasmids pTiB6S3 and pRiA4b. It has
      three open reading frames (repA, repB, repC) and a conserved intergenic sequence.

PMID- 8566713
TI  - Characterization of the smtA gene encoding an S-adenosylmethionine-dependent
      methyltransferase of Escherichia coli.
AB  - The mukB operon is located at 21 min on the Escherichia coli chromosome and seems
      to consist of four genes, orf30 (smtA), mukF, mukE, and mukB. Based on sequence
      similarity, the promoter-proximal gene, orf30 (smtA), could encode an S
      adenosylmethionine-dependent methyltransferase. The smtA gene is not essential
      for cell growth and its expression is positively regulated by H-NS, an
      Escherichia coli histone-like protein.

PMID- 8566714
TI  - Transcriptional analysis of the beta-galactosidase gene (pbg) in Clostridium
      perfringens.
AB  - The mode of expression of the beta-galactosidase gene (pbg) of Clostridium
      perfringens was examined. The pbg gene was transcribed on a single 3.7-kb mRNA.
      The transcript contained a message for ORF54, located upstream of the pbg gene in
      the chromosome, indicating that ORF54 and the pbg gene comprise one operon (pbg
      operon). Expression of the pbg operon was induced by lactose at the
      transcriptional level. The promoter structure of the pbg operon was characterized
      by many palindrome structures and direct repeats, which suggests that there might
      be some catabolite regulation of the expression of the pbg operon in C.
      perfringens.

PMID- 8566715
TI  - Use of species- and strain-specific PCR primers for identification of conifer
      root-associated Bacillus spp.
AB  - A polymerase chain reaction amplification of 23S rDNA was developed to identify
      Bacillus spp. recovered from roots, mycorrhizae, and rhizosphere soil of
      conifers. The polymerase chain reaction incorporated a conserved 23S rDNA forward
      primer in combination with a reverse primer designed to hybridize exclusively to
      nucleotide sequences of either B. polymyxa or B. mycoides. The amplification
      provided a rapid and simple means of identifying DNA from isolates of Bacillus,
      and could be used directly on whole Bacillus cells or mixed populations. The
      reaction was used to detect and differentiate these Gram-positive species from
      agar plates inoculated with samples from various conifer samples. A strain
      specific primer was also synthesized and used to identify Bacillus which were
      established within conifer roots 4 weeks after inoculation.

PMID- 8566716
TI  - An iron-dependent mutant of Listeria monocytogenes of attenuated virulence.
AB  - A bank of Tn917-insertional mutants from the facultative intracellular pathogen
      Listeria monocytogenes was screened by an original method based on bacterial
      growth on synthetic medium under iron-limiting conditions. One mutant, whose in
      vitro growth in synthetic medium was specifically dependent upon the availability
      of iron in its environment, was isolated and characterized. The insertional event
      occurred in a non-coding region, upstream of a rrn operon and located within a
      1100-kb NotI fragment of the physical map, where the virulence genes already
      identified in L. monocytogenes were also present. Protein analysis by SDS-PAGE
      revealed a pleiotropic effect of the insertional event on cell-associated
      proteins, suggesting a polar effect of the transposon on adjacent unknown
      gene(s). The virulence in the mouse of this mutant was strongly impaired,
      although it was capable in vitro of growing intracellularly and of spreading from
      cell to cell, as shown by the production of lytic plaques on cell culture.

PMID- 8566717
TI  - Analysis of beta-ketothiolase and acetoacetyl-CoA reductase genes of a
      methylotrophic bacterium, Paracoccus denitrificans, and their expression in
      Escherichia coli.
AB  - The beta-ketothiolase gene (phaA) and acetoacetyl-CoA reductase gene (phaB) were
      isolated from Paracoccus denitrificans. Nucleotide sequence analysis showed that
      they encoded proteins of 391 amino acids with a molecular mass of 40,744 Da and
      of 242 amino acids with a molecular mass of 25,614 Da, respectively. The
      predicted gene products exhibited high amino acid identities with those from
      other bacteria: 64.4-74.0% for the phaA gene product and 47.6-80.6% for the phaB
      gene product, respectively. Both genes were co-transcribed in a recombinant
      Escherichia coli. In addition, promoter activity was detected upstream of the
      phaA gene. Hence, the two genes are organized as an operon, phaA-phaB, in P.
      denitrificans. NADH was preferred to NADPH as a cofactor of acetoacetyl-CoA
      reductase.

PMID- 8566718
TI  - Sequence analysis of the region upstream of a peptidoglycan hydrolase-encoding
      gene from bacteriophage phi 11 of Staphylococcus aureus.
AB  - The nucleotide sequence of a 1.1-kb DNA fragment upstream of a peptidoglycan
      hydrolase-encoding gene (lytA) from bacteriophage phi 11 of Staphylococcus aureus
      was determined to see if the upstream sequences are involved in the transfer of
      the lytA product through the cytoplasmic membrane. Sequencing revealed three open
      reading frames of 171, 147 and 435 bp with consensus Shine-Dalgarno sequences
      located upstream from the ATG start codons. The third open reading frame overlaps
      with the 5' end of lytA by 18 nucleotides. Comparison of the deduced amino acid
      sequences of the open reading frames with the amino acid sequences in the NCBI
      Entrez database did not show any significant homology to any sequenced
      polypeptides. However, the analysis of the peptides showed some structural
      similarities to the product of the holin gene family. Lysogens containing an
      insertional mutation in ORF3, upon induction, produced either no phage titer or
      very low phage titers, compared to the wild-type lysogen. Transformation of ORF3
      mutated lysogens by a plasmid containing the intact ORF3 produced the same phage
      titer as wild-type lysogen, suggesting that the ORF3 product is involved in the
      process of cell lysis/phage release.

PMID- 8566719
TI  - Rapid identification of Acremonium lolii and Acremonium coenophialum endophytes
      through arbitrarily primed PCR.
AB  - Using a random decamer 5'-CCGAGGTGAC-3' in an arbitrarily primed PCR, similar
      band patterns were observed between Acremonium lolii and A. coenophialum DNA,
      which were somewhat different from those formed by other fungal DNA. Despite
      sharing bands of around 0.7, 0.9 and 2.1 kb, A. lolii can be distinguished from
      A. coenophialum by the presence of an additional band at around 0.5 kb in the
      arbitrarily primed PCR.

PMID- 8566720
TI  - The outcome of Stevens-Johnson syndrome treated with corticosteroids.
AB  - Stevens-Johnson Syndrome (SJS) may have considerable morbidity and mortality.
      Traditional management has been supportive with or without corticosteroids, and
      we have previously reported our successful experience treating 41 SJS patients
      with corticosteroids. We now report the outcome of prospectively treating 13
      additional patients with SJS with high doses of corticosteroids. Thirteen
      consecutive patients with SJS were treated with corticosteroids at diagnosis.
      Their clinical course and outcomes were analyzed. Drug reactions were potential
      precipitants of SJS in 12 patients. The percent of skin involvement ranged from
      30% to 90% with eight patients having greater than 80% involvement. Bullous
      lesions were seen in two patients. All patients made a complete recovery.
      Corticosteroid therapy may be lifesaving in these patients; and in our
      experience, early management of SJS with high dose corticosteroids has been very
      effective and associated with a full recovery.

PMID- 8566721
TI  - Virus induced erythema multiforme and Stevens-Johnson syndrome.
AB  - Erythema Multiforme is an acute, self-limited inflammatory cutaneous disorder
      characterized by distinctive target lesions. Stevens-Johnson syndrome (SJS) is
      defined as severe erythema multiforme with mucosal involvement, visceral
      involvement, or both. Both diseases are part of a continuum of immunologically
      mediated mucocutaneous diseases at various grades of severity. Viral infections
      are known triggers of these skin disorders. We report the success of a management
      strategy of acyclovir and prednisone for herpes simplex virus-associated erythema
      multiforme. In addition we describe the apparent first case of primary varicella
      infection as a direct cause of SJS. The two cases are presented and a single-case
      statistical analysis has been employed to evaluate the significance of the
      management protocol. The method of analysis is presented in the appendix. When a
      patient with primary varicella infection develops bullous lesions, SJS should be
      considered in the differential diagnosis, as early and intense corticosteroid
      therapy may be lifesaving. A regimen of prophylactic acyclovir and therapy for an
      exacerbation of herpetic lesions with acyclovir and prednisone was effective in
      inducing significant control of recurrent erythema multiforme secondary to herpes
      simplex in our patient.

PMID- 8566722
TI  - Immunopathology of Stevens-Johnson syndrome.

PMID- 8566723
TI  - Limited coronal CT: an alternative screening examination for sinonasal
      inflammatory disease.
AB  - Coronal CT is the definitive procedure for radiologic evaluation of sinonasal
      inflammatory disease, yet many clinicians rely on the less expensive plain film
      sinus series. We designed a limited four slice coronal CT and prospectively
      compared it with conventional coronal CT and plain film sinus series in 25
      patients to determine whether a limited CT examination is a suitable alternative
      to these other radiologic procedures in screening for sinonasal inflammatory
      disease. The presence, amount, and location of mucous membrane disease,
      opacification, air fluid levels, retention cysts, erosions, and anomalies were
      recorded for each technique. The limited CT agreed with the complete CT in 82% of
      the 200 sinus compartments reviewed. Localized disease, usually mucosal
      thickening of 3 mm or less and missed on the limited CT, but detected on the
      complete CT, accounted for 22 of 36 errors of interpretation. Underestimation of
      mucosal disease, usually 2 mm or less, accounted for eight errors and
      misinterpretation of partial volume effect for three errors. Using complete CT a
      s the established standard, plain film missed 37 instances of disease detected on
      the limited CT; 73% involved an error of mucosal thickening 4 mm or greater. A
      limited coronal CT of the paranasal sinuses offers a potentially lower cost
      alternative to complete CT in screening for sinonasal inflammatory disease. It is
      more accurate than plain film series. Localized disease and osteomeatal disease
      is underestimated with the current protocol, and so a limited CT should not be
      used for evaluating potential cancer patients or for surgical planning.

PMID- 8566724
TI  - IRINE symposium; immunologic advances in the Commonwealth of Independent
      States(Part 1).
AB  - This symposium describes the advances in immunology that have occurred in the
      Commonwealth of Independent States. The worldwide difficulties of allergists and
      immunologists who face problems including increasing morbidity and mortality from
      HIV, immunoregulatory disorders, and asthma are also germane to our colleagues in
      Russia, Belarus, and Ukraine. The unique experiences of Dr. Petrov, who has
      investigated novel immunomodulators; Dr. Titov, who has studied synthetic
      immunogens; Dr. Babakhin, who has investigated the effects of modified allergens;
      and Dr. Sidorovitch, who has explored the pathogenesis and natural history of HIV
      infections occurring in Russia, offer interesting insights into the advances in
      immunology that have occurred in the Commonwealth of Independent States. Coping
      with the tragedies of radiation from Chernobyl and environmental pollution in
      Ukraine, Drs. Titov and Markov have investigated the effects of these unfortunate
      disruptions of the environment upon the occurrence of immunoregulatory disorders
      and asthma, respectively. Under the direction of Drs. Petrov and Khaitov,
      immunologist from the Commonwealth of Independent States, have conducted studies
      that are among the leading epidemiological immune investigations of our time to
      determine the effects of the Chernobyl radiation on the immune system.

PMID- 8566725
TI  - Myelopeptides: new immunoregulatory peptides.
AB  - Bone marrow cells of various animal species and humans produce a group of
      bioregulatory peptides called myelopeptides (MPs). MPs have been isolated and
      purified, and their physico-chemical properties have been investigated. MPs have
      a wide spectrum of functional activities: immunoregulatory, differentiating, and
      opiate-like. A new immunocorrective drug, Myelopidum, which is used effectively
      in clinical practice for treating diseases accompanied by immunodeficiency, has
      been created on the basis of MPs. Administration of Myelopidum after surgery
      prevents 50% to 70% of postsurgical complications, particularly postsurgery
      pneumonia, and also normalizes the number and balance of T-helper cells, T
      suppressor cells, and B-lymphocytes in patients with chronic pulmonary diseases,
      resulting in a beneficial clinical effect, including a significant prolongation
      of remission periods. Myelopidum is also used in veterinary medicine for
      prophylaxis and treatment of pneumonia and enteritis in newborn and young
      animals. The primary structure of several myelopeptides is established. The
      functional activities of two, MP-1 (Phe-Leu-Gly-Phe-Pro-Thr) and MP-2 (Leu-Val
      Val-Tyr-Pro-Trp), are being investigated.

PMID- 8566726
TI  - Effects of radiation on the production of immunoglobulins in children subsequent
      to the Chernobyl disaster.
AB  - Studies on the immediate and long-term effects of radiation on the B-system
      immunity of children who were affected by radiation after the Chernobyl disaster
      (from 1986-1992) are summarized in this paper. Complete clinical and
      immunological examination of more than 6000 children have been carried out. The
      dynamics of the immune system, with ongoing reactions of cell proliferation and
      differentiation, gene amplification, transcription, translation, biosynthesis and
      switching production of isotypes and subclasses of immunoglobulins, as well as
      specific and nonspecific (natural) antibodies, make it highly susceptible to the
      action of radiation in addition to other ecological factors. B-system of immunity
      (B-cel level, concentration of immunoglobulins-M, G, A, E; subclasses of IgG
      (IgG1-IgG4) in the serum and saliva, and the level of nonspecific heterophilic
      autoantibodies (RF, antithyroglobulin) were investigated in children of differing
      ages and sex living in the territories of the Republic of Belarus contaminated
      with radionuclides. Research showed decreased levels of B-cell and IgM and IgG
      isotopes 40-50 days after the disaster and increased levels of IgA
      immunoglobulins at that time. Long-term effects of low doses of radiation showed
      increased concentrations of IgM and IgG, correlating changes in the B-system of
      immunity with the level of 137Cs contamination in the territory of residence and
      also with the amount of 137Cs found in the children.

PMID- 8566727
TI  - Modified allergen immunotherapy: effect on immunoglobulin E production.
AB  - New forms of allergen immunotherapy are proposed employing modified allergens
      that induce T-cell responses without associated increased IgE-related responses.
      Synthetic polyelectrolytes attached to an analyte amy modulate T- and B-cell
      function, producing effective desensitization and altering immunoglobulin
      production dependent on the physico-chemical nature of the carrier molecule.

PMID- 8566728
TI  - Immunopathogenesis of HIV infection: a specific anti-HIV tolerance as a mechanism
      of control of disease progression.
AB  - The pathogenesis of HIV has been evaluated by many investigators, yet the precise
      reasons for certain patients developing lethal infection while others appear to
      live for long periods tolerating the HIV virus remain to be determined. The
      immune response to HIV may be critical in the development of the fatal infected
      stated, while tolerance of the HIV virus may allow longer-term survival despite
      infection. The mechanisms for failure of immune protection from HIV and the
      subsequent development of immunodeficiency are likely related to the very nature
      of the immune response to the initial HIV infection.

PMID- 8566729
TI  - Lucius Annaeus Seneca (4 B.C.-79 A.D.) Roman orator, author, and statesman.

PMID- 8566730
TI  - Pliny the Elder (23-65 A.D.) Roman historian and encyclopedist.

PMID- 8566731
TI  - Al-Afdal (1169-1225) Arab Sultan of Damascus and Egypt.

PMID- 8566732
TI  - Henri de Mondeville (1260-1320) French pioneer surgeon.

PMID- 8566733
TI  - The regulation of normal lung function.
AB  - The regulation of breathing is dependent on the complex interaction of three
      components of the respiratory system: 1) the control centers, 2) the sensors, and
      3) the effector organs. The control centers reside in the brainstem and are
      responsible for the automaticity of breathing. Input into these respiratory
      centers can be initiated from higher brain centers in order to produce voluntary
      breathing efforts. Afferent neural signals also come to the central control
      system from the respiratory sensors, which are divided into two categories:
      chemoreceptors and sensory receptors. The chemoreceptors respond to changes in
      the blood oxygen, carbon dioxide, and hydrogen ion concentration by sending
      impulses to the control center to alter the ventilatory pattern by affecting the
      effector organs--the respiratory muscles. The sensory receptors are located in
      the upper and lower airways, the lung, and the muscles of respiration. They also
      can have a marked effect on the respiratory pattern. It is believed that
      stimulation of these receptors is important in the initiation of hyperventilation
      and cough in lung diseases such as asthma. There is also recent evidence that
      respiratory chemoreceptor responsiveness is abnormal in patients with asthma who
      have a history of near-fatal attacks.

PMID- 8566734
TI  - Neural receptors and asthma.
AB  - Neurotransmitters released from sensory, parasympathetic, and sympathetic nerves
      regulate epithelial, vascular, glandular, and contractile processes in the human
      respiratory tract. The actions of these neurotransmitters are dependent upon the
      distribution and subtypes of their specific receptors expressed on the resident
      cells in the respiratory tract. The distributions of these receptors, and their
      potential activities in asthma, will be investigated with the hope of
      discriminating between the pharmacological and physiological actions of mediators
      and neurotransmitters in normal and asthmatic airways.

PMID- 8566735
TI  - B2 agonists and their safety in the treatment of asthma.
AB  - Increasing prevalence and severity of asthma has prompted the development and
      promulgation of various national and international guidelines for asthma
      management in adults and children. All of these guidelines agree that short
      acting inhaled B2-agonists on demand represent the most appropriate initial
      bronchodilator therapy. However, there has been considerable debate as to the
      merit of maintenance bronchodilator therapy with regular inhaled B2-agonists,
      either the short acting agents, or the newer long-acting inhaled B2-agonist,
      salmeterol. Of concern is the possibility that there are detrimental effects of
      chronic B2-agonist bronchodilator treatment. Do these B2-agonists have the
      potential to worsen asthma control and thereby have an adverse impact by
      contributing to the increased prevalence and severity of asthma? This article
      will review the pertinent literature with regard to the safety of the B2
      agonists, which are appropriate but not perfect medications for asthmatics. It
      will also put this information in perspective for the clinician and provide this
      author's recommendations for their use in managing the manifestations of chronic
      and recurrent asthma.

PMID- 8566736
TI  - Prevalence of avocado allergy among atopic patients.
AB  - A 41-year-old woman with known food allergy to avocado was treated for
      anaphylaxis after eating a meal containing avocado. This prompted a study to
      determine the prevalence of avocado induced symptoms and skin reactivity in a
      group of atopic patients. One hundred consecutive atopic patients with allergic
      rhinitis undergoing skin testing before initiation of immunotherapy were also
      prick skin tested to avocado. Patients with symptoms upon avocado ingestion were
      also assessed for specific serum IgE antibodies to avocado. Of the 100 atopic
      patients not selected for avocado sensitivity, 21 had positive prick skin tests
      to avocado. Eight of the 21 avocado skin test positive patients reported that
      symptoms repeatedly followed the ingestion of avocado; two reported systemic
      reactions, but six noted oral symptoms only. Serum IgE antibodies to avocado were
      elevated in seven of the eight patients reporting symptoms after eating avocado.
      Seven of the eight patients also reported oral symptoms following cantaloupe
      ingestion. Four reported similar symptoms upon eating banana. Avocado-induced
      symptoms occurred in 8% of 100 consecutive atopic allergic rhinitis patients
      unselected for avocado reactivity. Oral, and less frequently systemic, allergy
      symptoms appear to be more common among the atopic population than previously
      appreciated.

PMID- 8566737
TI  - Lessons and myths regarding cross-reacting foods.

PMID- 8566738
TI  - Acute allergic disease in a hospital emergency room: a retrospective evaluation
      of one year's experience.
AB  - Efforts at understanding the patterns and prevalence rates of various causes of
      anaphylaxis are needed. This report is a first effort to address the issue and
      review the experiences of one voluntary hospital emergency room, where records
      from 326 (1.4%) of 23,647 emergency room reports for 1992 were analyzed. These
      results are compared to other already published results. Further study, on a
      national basis, is clearly necessary. It was remarkable that only 13/48 (27%) bee
      sting allergic patients were given self-injectable epinephrine and only 6/48
      (12.5%) of these patients were referred to an allergist. Further, none of 165
      other patients was referred to an allergist.

PMID- 8566740
TI  - Molecular bases for the construction of artificial immunogens and vaccines based
      on synthetic polyions.
AB  - The molecular and cellular mechanisms of action of synthetic polyions on
      immunogenesis are reviewed. The results of studies of principal properties of
      polyionic immunostimulators and of the cell responses to the action of these
      stimulants have been used to construct artificial antigen-polyion complexes with
      enhanced immunogenic properties. The immunizing properties of such macromolecular
      complexes, constructed with the use of bacterial or viral antigens, are analyzed.

PMID- 8566739
TI  - Tolerability of imidazole salycilate in aspirin-sensitive patients.
AB  - Over the last few years, many studies have been carried out in order to
      individualize which nonsteroidal anti-inflammatory drug (NSAID) can be tolerated
      in aspirin sensitivity. Imidazole salicylate (IS) is a new NSAID that inhibits
      Tromboxane A2 synthesis, without interferring with cyclo-oxygenase pathway, whose
      inhibition was demonstrated to cause asthma and/or urticaria/angioedema in
      aspirin-sensitive patients. We enrolled 67 subjects with documented intolerance
      to aspirin, pyrazolones or NSAIDs, clinically manifested as urticaria/angioedema
      (68%), asthma, and/or rhinitis (32%). A challenge with IS was carried out in
      every patient in single-blind fashion, reaching a cumulative dosage of 1000 mg in
      the fourth session. No appearance of urticaria or bronchospastic reactions was
      registered in any subject, confirming the safe use of IS in aspirin-sensitive
      patients.

PMID- 8566741
TI  - Immunological properties of allergen chemically modified with synthetic copolymer
      of N-vinylpyrrolidone and maleic anhydride.
AB  - Several conjugates of model allergen ovalbumin (OA) and the copolymer of N-vinyl
      pyrrolidone and maleic anhydride (VMA) modified with epsilon-aminocaproic acid
      (Acp) were prepared in different OA/Acp-VMA ratios. All conjugates were separated
      by ultrafiltration and analyzed by HPLC. Their compositions were determined by
      amino acid analysis and UV spectrometry. To detect immunogenicity, all conjugates
      were injected intraperitoneally into (CBAxC57BL/6)F1 mice three times in 3-week
      intervals in OA doses equivalent to 0.5, 10, and 100 micrograms/mouse. Only the
      conjugate containing 20%OA (OA(20%)-Acp-VMA) did not induce significant
      quantities of anti-OA IgE, but did induce anti-OA IgG antibodies in dose
      dependent manner comparable to that of unmodified OA. Mixtures of OA and Acp-VMA
      or OA modified only with VMA without Acp activation with Acp induced dose
      dependent anti-OA IgE and IgG antibody formation comparable to that of OA. Using
      passive cutaneous anaphylaxis, RAST inhibition and leukocyte histamine release, a
      significant reduction of allergenicity was noted using OA(20%)-Acp-VMA. This
      conjugate stimulated activation of the OA-specific T-cell hybrid 3DO-548
      comparable to that of unconjugated OA. During experimental allergen-specific
      hyposensitization with OA(20%)-Acp-VMA, suppression of anti-OA IgE response and
      elevation of anti-OA IgG responses were noted when compared with unmodified OA.
      Selective blockade of B-cell epitopes of allergen may occur using the carrier Acp
      VMA to reduce allergenicity while not affecting T-cell epitopes, thereby
      preserving immunogenicity. This approach of chemical modification of allergen
      suggests new opportunities in the creation of preparations for allergen-specific
      immunotherapy.

PMID- 8566742
TI  - The problem of asthma in the Ukraine.
AB  - Although health statistics in Ukraine are difficult to obtain, there does appear
      to be an increase in the occurrence of asthma. Overall reporting of asthma is
      less frequent than in Western Europe, perhaps due to insufficient diagnostic
      capabilities at the present time. Asthma therapy in the Ukraine tends toward the
      use of theophylline and beta 2-agonists, rather than inhaled corticosteroids.
      Asthma morbidity differs in various regions of Ukraine, perhaps as a consequence
      of increased environmental exposure in some areas.

PMID- 8566743
TI  - John Calvin (1509-1564) French churchman and religious reformer.

PMID- 8566744
TI  - John Hamilton (1511-1571) Scottish Archbishop.

PMID- 8566745
TI  - Jean Baptista van Helmont (1579-1644) Belgian physician and pioneer chemist.

PMID- 8566746
TI  - Jean Riolan (1580-1657) French physician and pioneer anatomist.

PMID- 8566747
TI  - Switching transcription on and off during the yeast cell cycle: Cln/Cdc28 kinases
      activate bound transcription factor SBF (Swi4/Swi6) at start, whereas Clb/Cdc28
      kinases displace it from the promoter in G2.
AB  - When yeast cells reach a critical size in late G1 they simultaneously start
      budding, initiate DNA synthesis, and activate transcription of a set of genes
      that includes G1 cyclins CLN1, CLN2, and many DNA synthesis genes. Cell cycle
      regulated expression of CLN1, CLN2 genes is attributable to the heteromeric
      transcription factor complex SBF. SBF is composed of Swi4 and Swi6 and binds to
      the promoters of CLN1 and CLN2. Different cyclin-Cdc28 complexes have different
      effects on late G1-specific transcription. Activation of transcription at the
      G1/S boundary requires Cdc28 and one of the G1 cyclins Cln1-Cln3, whereas
      repression of SBF-regulated genes in G2 requires the association of Cdc28 with G2
      specific cyclins Clb1-Clb4. Using in vivo genomic footprinting, we show that SBF
      (Swi4/Swi6) binding to SCB elements (Swi4/Swi6 cell cycle box) in the CLN2
      promoter is cell cycle regulated. SBF binds to the promoter prior to the
      activation of transcription in late G1, suggesting that Cln/Cdc28 kinase
      regulates the ability of previously bound SBF to activate transcription. In
      contrast, SBF dissociates from the CLN2 promoter when transcription is repressed
      during G2 and M phases, suggesting that Clb1-Clb4 repress SBF activity by
      inhibiting its DNA-binding activity. Switching transcription on and off by
      different mechanisms could be important to ensure that Clns are activated only
      once per cell cycle and could be a conserved feature of cell cycle-regulated
      transcription.

PMID- 8566748
TI  - Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the
      induced differentiation of the myelomonocytic cell line U937.
AB  - The hormonal form of vitamin D, 1,25-dihydroxyvitamin D3, acting through its
      cognate nuclear receptor (vitamin D3 receptor, VDR) will induce myeloid leukemic
      cell lines to terminally differentiate into monocytes/macrophages. Because VDR
      acts by transcriptionally regulating responsive genes in a ligand-dependent
      manner, we sought target genes of the receptor that initiate, the differentiation
      process in response to ligand. We screened a cDNA library prepared from the
      myelomonocytic U937 cell line with probes generated from either 1,25
      dihydroxyvitamin D3-treated or untreated cells. We report here that a candidate
      clone that hybridized differentially is the Cdk inhibitor p21WAF1, CIP1.
      Furthermore, we show that p21 is transcriptionally induced by 1,25
      dihydroxyvitamin D3 in a VDR-dependent, but not p53-dependent, manner, and we
      identify a functional vitamin D response element in the p21 promoter. Transient
      overexpression of p21 and/or the related Cdk inhibitor p27 in U937 cells in the
      absence of 1,25-dihydroxyvitamin D3 results in the cell-surface expression of
      monocyte/macrophage-specific markers, suggesting that ligand-modulated
      transcriptional induction of the p21 gene facilitates the induced differentiation
      of this monoblastic cell line. We believe that this is the first report
      demonstrating that the ectopic overexpression of a Cdk inhibitor such as p21 or
      p27 directly leads to a terminal differentiation program.

PMID- 8566749
TI  - Differential effects of an erythropoietin receptor gene disruption on primitive
      and definitive erythropoiesis.
AB  - Although the hormone erythropoietin (Epo) and its receptor (EpoR) are known to
      play important roles in the regulation of erythropoiesis, several questions
      remain concerning the developmental role of Epo/EpoR signaling. As the functions
      of Epo have been defined primarily through studies of definitive erythroid cells,
      its importance for primitive, embryonic erythropoiesis remains uncertain, as does
      the significance of EpoR expression in several nonerythroid cell types. To
      address these questions, mouse embryonic stem cells and embryos lacking a
      functional EpoR gene were produced by gene targeting. The effects of the mutation
      were examined in embryos developing in vivo, in chimeric adult mice produced with
      homozygous mutant embryonic stem cells, and in hemopoietic cells cultured in
      vitro. No defects were apparent in nonerythroid cell lineages in which the EpoR
      normally is expressed, including megakaryocytes and endothelial cells. In the
      mutant yolk sac, primitive erythrocytes were produced in normal numbers, they
      underwent terminal differentiation, and expressed near normal levels of embryonic
      globins, although they were reduced in size and their proliferation was severely
      retarded after E9.5. In contrast, in the fetal liver, definitive erythropoiesis
      beyond the late progenitor (CFU-E) stage was drastically inhibited by the EpoR
      mutation, and virtually no definitive erythrocytes were produced in vivo, leading
      to embryonic death by E13.5. Thus, our results suggest a fundamental difference
      in the molecular mechanisms stimulating primitive and definitive erythropoiesis.
      It was also observed that a few mutant definitive erythroid cells could
      terminally differentiate when cultured with additional cytokines, demonstrating
      that although Epo/EpoR signaling is important for definitive erythroid cell
      survival and proliferation, it is not an obligatory step in differentiation.

PMID- 8566750
TI  - Keratinocyte growth factor is required for hair development but not for wound
      healing.
AB  - Keratinocyte growth factor (KGF), also known as fibroblast growth factor 7
      (FGF7), is synthesized by skin fibroblasts. However, its mitogenic activity is on
      skin keratinocytes, where it is the most potent growth factor identified thus
      far. To explore KGF's function in vivo, we used embryonic stem cell technology to
      generate mice lacking KGF. Over time, their fur developed a matted appearance,
      very similar to that of the rough mouse, whose recessive mutation maps at or near
      the KGF locus on mouse chromosome 2. In contrast to the recently reported
      transforming growth factor-alpha (TGF-alpha) and FGF5 knockouts, which showed
      defects in the follicle outer-root sheath and the hair growth cycle,
      respectively, the hair defect in the KGF knockout seemed to be restricted to the
      cells giving rise to the hair shaft. Thus, we have uncovered a third, and at
      least partially nonoverlapping, growth factor pathway involved in orchestrating
      hair follicle growth and/or differentiation. Surprisingly, the absence of KGF
      resulted in no abnormalities in epidermal growth or wound healing. This was true
      even when we engineered double knockout mice, null for both KGF and TGF-alpha,
      two factors that are increased dramatically in the normal wound-healing process.
      Whereas we found no evidence of compensatory changes at the mRNA level of wounded
      knockout mice, these data imply that the regulation of epidermal growth is
      complex and involves a number of growth stimulatory factors that go beyond what
      are thought to be the major paracrine and autocrine growth factors. We suggest
      that the redundancy in epidermal growth and wound healing is likely to stem from
      the vitality of these functions to the organism, a feature that is not a
      consideration for the hair follicle.

PMID- 8566751
TI  - Rescue of Drosophila labial null mutant by the chicken ortholog Hoxb-1
      demonstrates that the function of Hox genes is phylogenetically conserved.
AB  - Hox complexes are important players in the establishment of the body plan of
      invertebrates and vertebrates. Sequence comparison demonstrates a remarkable
      phylogenetic conservation of key structural features of Hox genes. The
      correlation between the physical order of genes along the chromosomes and their
      domains of function along the body axis is conserved between arthropods and
      vertebrates. Ectopic expression experiments suggest that the functions of homeo
      proteins also are conserved between invertebrates and vertebrates. However, it
      remains an open question whether vertebrate Hox genes expressed under the control
      of Drosophila regulatory sequences can substitute the function of Drosophila Hox
      genes. We have studied this issue with the Drosophila labial (lab) gene and its
      chicken ortholog gHoxb-1. We fused the entire protein-coding region of gHoxb-1
      with previously identified regulatory sequences of lab. This approach places
      gHoxb-1 into the normal embryonic spatiotemporal context in which lab acts. Ten
      transgenic lines carrying gHoxb-1 were established and tested for their ability
      to rescue lab null mutant animals. Eight lines rescued with high efficiency,
      embryonic lethality, and abnormal head morphogenesis, two defects observed in lab
      null mutant embryos. The rescue with the gHoxb-1 minigene was close to the
      efficiency of that obtained with the Drosophila lab minigene. This indicates that
      gHoxb-1 protein can regulate lab target genes and thereby restore embryonic
      viability. This is striking, as Lab and gHoxb-1 proteins are divergent except for
      their homeo domains and a short stretch of amino acids amino-terminal to the
      homeo domain. Our findings demonstrate a functional conservation of the lab class
      homeo proteins between insects and vertebrates and support the view that function
      of Hox genes resides in relatively few conserved motifs and largely in the homeo
      domain.

PMID- 8566752
TI  - Transcriptional enhancers act in cis to suppress position-effect variegation.
AB  - We have examined the basis of enhancer effects on gene expression by altering the
      action of enhancers on expression of a stably integrated reporter gene. We used
      two distinct experimental approaches: recombinase-mediated deletion of an
      enhancer and modulation of the activity of another enhancer composed of
      downstream metal response elements (MREs). The flp recombinase was used to delete
      the 5'HS2 globin enhancer from a site downstream of beta-geo at nine separate
      integration sites in K562 erythroleukemia cells. In no case does deletion of
      5'HS2 have a significant effect on the level of expression; however, the deletion
      does increase dramatically the rate at which expression of beta-geo is silenced.
      Zinc stimulation of a metallothionein enhancer has no effect on the level of
      reporter expression, but slows the rate of silencing. Silencing in both cases is
      highly site dependent, and resembles position-effect variegation (PEV). These
      results strongly support a binary mode of enhancer action, as in both cases the
      enhancer maintains reporter expression without a strong effect on the level of
      expression. Taken together, these findings suggest that transcriptional
      activators have a direct interaction with repressive chromatin structures, which
      is independent of an effect on the rate of transcription. We propose that cis
      acting transcriptional control elements may act primarily through this mechanism.

PMID- 8566753
TI  - Adenovirus replication is coupled with the dynamic properties of the PML nuclear
      structure.
AB  - Wild-type PML and at least four other novel proteins are localized within
      discrete nuclear structures known as PODs. We demonstrate here that during
      adenovirus infection, immediate early viral proteins from the E1 and E4
      transcription units associate with the POD, which in turn undergoes a dramatic
      morphological change. During this process, the auto-antigen Sp-100 and NDP55 but
      not PML, relocate from the POD to the viral inclusion bodies, the sites of
      adenovirus DNA replication and late RNA transcription. The E4-ORF3 11-kD protein
      alone will induce this reorganization and reciprocally, viruses carrying
      mutations in the E4-domain fail to do so. These same viral mutants are defective
      in viral replication as well as the accumulation of late viral mRNAs and host
      cell transcription shutoff. We show that interferon (INF) treatment enhances the
      expression of PML, reduces or blocks PODs reorganization, and inhibits BrdU
      incorporation into viral inclusion bodies. In addition, cell lines engineered to
      overexpress PML prevent PODs from viral-induced reorganization and block or
      severely delay adenovirus replication. These results suggest that viral
      replication relies on components of the POD and that the structure is a target of
      early viral proteins.

PMID- 8566754
TI  - An intron enhancer recognized by splicing factors activates polyadenylation.
AB  - Alternative processing of the pre-messenger RNA encoding calcitonin/calcitonin
      gene-related peptide (CT/CGRP) involves alternative inclusion of a 3'-terminal
      exon (exon 4) embedded within a six exon primary transcript. Expression of
      CT/CGRP in transgenic mice indicates that inclusion of exon 4 occurs in a wide
      variety of tissues, suggesting that the factors responsible for exon 4 inclusion
      are widely distributed. Inclusion of exon 4 requires an enhancer sequence located
      within the intron downstream of the poly(A) site of exon 4. Here we show that the
      intron enhancer activated in vitro polyadenylation cleavage of precursor RNAs
      containing the CT/CGRP exon 4 poly(A) site or heterologous poly(A) sites. To our
      knowledge this is the first example of an intron-located enhancer that
      facilitates polyadenylation. Within the enhancer sequence is a 5' splice site
      sequence immediately preceded by a pyrimidine tract. This 5' splice site sequence
      was required for enhanced polyadenylation and was recognized by both U1 small
      nuclear ribonucleoproteins (snRNPs) and alternative splicing factor/splicing
      factor 2 (ASF/SF2). Enhancement of polyadenylation required U1 RNA, suggesting
      that the 5' splice site sequence within the enhancer mediates enhancement via
      interaction with factors normally associated with functional 5' splice sites.
      Mutation of the polypyrimidine track of the enhancer also inhibited in vitro
      polyadenylation cleavage. Oligonucleotide competitions and UV cross-linking
      indicated that the enhancer pyrimidine track binds the polypyrimidine tract
      binding protein (PTB), but not U2 snRNP auxiliary factor (U2AF), and that binding
      of PTB was required for maximal enhancer-mediated polyadenylation. These results
      suggest that the enhancer binds known splicing factors, and that binding of these
      factors activates polyadenylation cleavage. Furthermore, these results suggest
      that regulation of alternative processing of CT/CGRP could occur at the level of
      polyadenylation, rather than splicing.

PMID- 8566755
TI  - CUS1, a suppressor of cold-sensitive U2 snRNA mutations, is a novel yeast
      splicing factor homologous to human SAP 145.
AB  - The function of U2 snRNA in splicing is mediated by the proteins of the U2 small
      nuclear ribonucleoprotein. To identify proteins that influence the function of U2
      snRNA we carried out a screen for mutations in Saccharomyces cerevisiae that
      suppress the cold-sensitive growth defect of a mutation in U2 stem loop IIa, a
      structure important for the stable association of the U2 snRNP with pre-mRNA. The
      screen identified three dominant suppressor genes, one of which, CUS1-54, encodes
      an essential splicing protein required for U2 snRNP addition to the spliceosome.
      The suppressor protein rescues the spliceosome assembly defect of the mutant U2
      in vitro, indicating that suppression is direct. Allele specificity tests show
      that the suppressor does not simply bypass the requirement for U2 stem loop IIa.
      Extra copies of wild-type CUS1, but not CUS1-54, suppress the temperature
      sensitive prp11 and prp5 mutations, linking CUS1 protein to a subset of other
      factors required at the same step of spliceosome assembly. CUS1 is homologous to
      SAP 145, a component of the mammalian U2 snRNP that interacts with pre-mRNA. The
      yeast genome also encodes a homolog of human SAP 49, a protein that interacts
      strongly with both SAP 145 and pre-mRNA, underscoring the conservation of U2
      snRNP proteins that function in spliceosome assembly.

PMID- 8566756
TI  - Evidence that sequence-independent binding of highly conserved U2 snRNP proteins
      upstream of the branch site is required for assembly of spliceosomal complex A.
AB  - A critical step in the pre-mRNA splicing reaction is the stable binding of U2
      snRNP to the branchpoint sequence (BPS) to form the A complex. The multimeric U2
      snRNP protein complexes SF3a and SF3b are required for A complex assembly, but
      their specific roles in this process are not known. Saccharomyces cerevisiae
      homologs of all of the SF3a, but none of the SF3b, subunits have been identified.
      Here we report the isolation of a cDNA encoding the mammalian SF3b subunit SAP
      145 and the identification of its probable yeast homolog (29% identity). This
      first indication that the homology between yeast and metazoan A complex proteins
      can be extended to SF3b adds strong new evidence that the mechanism of A complex
      assembly is highly conserved. To investigate this mechanism in the mammalian
      system we analyzed proteins that cross-link to 32P-site-specifically labeled pre
      mRNA in the A complex. This analysis revealed that SAP 145, together with four
      other SF3a/SF3b subunits, UV cross-links to pre-mRNA in a 20-nucleotide region
      upstream of the BPS. Mutation of this region, which we have designated the
      anchoring site, has no apparent effect on U2 snRNP binding. In contrast, when a
      2'O methyl oligonucleotide complementary to the anchoring site is added to the
      spliceosome assembly reaction, A complex assembly and cross-linking of the
      SF3a/SF3b subunits are blocked. These data indicate that sequence-independent
      binding of the highly conserved SF3a/SF3b subunits upstream of the branch site is
      essential for anchoring U2 snRNP to pre-mRNA.

PMID- 8566757
TI  - A dot-matrix program with dynamic threshold control suited for genomic DNA and
      protein sequence analysis.
AB  - Graphical dot-matrix plots can provide the most complete and detailed comparison
      of two sequences. Presented here is DOTTER2, a dot-plot program for X-windows
      which can compare DNA or protein sequences, and also DNA versus protein. The main
      novel feature of DOTTER is that the user can vary the stringency cutoffs
      interactively, so that the dot-matrix only needs to be calculated once. This is
      possible thanks to a 'Greyramp tool' that was developed to change the displayed
      stringency of the matrix by dynamically changing the greyscale rendering of the
      dots. The Greyramp tool allows the user to interactively change the lower and
      upper score limit for the greyscale rendering. This allows exploration of the
      separation between signal and noise, and fine-grained visualisation of different
      score levels in the dot-matrix. Other useful features are dot-matrix compression,
      mouse-controlled zooming, sequence alignment display and saving/loading of dot
      matrices. Since the matrix only has to be calculated once and since the algorithm
      is fast and linear in space, DOTTER is practical to use even for sequences as
      long as cosmids. DOTTER was integrated in the gene-modelling module of the
      genomic database system ACEDB3. This was done via the homology viewer BLIXEM in a
      way that also allows segments from the BLAST suite of searching programs to be
      superimposed on top of the full dot-matrix. This feature can also be used for
      very quick finding of the strongest matches. As examples, we analyse a
      Caenorhabditis elegans cosmid with several tandem repeat families, and illustrate
      how DOTTER can improve gene modelling.

PMID- 8566758
TI  - Sequence and transcriptional analysis of a DNA region involved in the production
      of capsular polysaccharide in Streptococcus pneumoniae type 3.
AB  - The nucleotide (nt) sequence of a 9704-bp EcoRI fragment of Streptococcus
      pneumoniae (Sp) type-3 DNA has been determined and found to contain one partial
      and five complete open reading frames (ORFs). One of these ORFs corresponds to
      the cap3 A gene coding for the UDP-glucose (UDPGlc) dehydrogenase which is
      directly responsible for the transformation of some unencapsulated serotype-3 Sp
      mutants to the encapsulated phenotype [Arrecubieta et al., J. Bacteriol. 176
      (1994) 6375-6383]. The two ORFs downstream from this gene (cap3B and cap3C)
      encode proteins with molecular masses of 49 and 34 kDa. Analysis of the deduced
      amino acid (aa) sequences of Cap3B and Cap3C shows homology to polysaccharide
      synthases and UDPG1c pyrophosphorylases, respectively. Furthermore, genetic
      complementation analysis showed that cap3C restored the galU defect of an
      Escherichia coli mutant. Northern blots have shown that cap3A, cap3B and cap3C
      constitute a single transcriptional unit, and primer extension analysis has
      revealed that the transcription start point is preceded by a nt sequence
      identical to the sigma 70 consensus promoter sequence of E. coli. The sequence
      upstream from this cluster also has a high degree of similarity with genes
      postulated to be essential for capsular production in several Gram+ bacteria.
      However, Northern blot analysis and insertion-duplication mutagenesis indicated
      that genes located in this region are not necessary for type-3 capsule production
      in the Sp strain 406.

PMID- 8566759
TI  - Structural organization of a Bacillus subtilis operon encoding menaquinone
      biosynthetic enzymes.
AB  - Menaquinone (MK) is a non-protein component of the Bacillus subtilis (Bs)
      electron transport chain synthesized from chorismate through a series of MK
      specific reactions. The genes encoding biosynthesis of the naphthoquinone ring of
      MK are clustered at 273 degrees on the Bs chromosome. A 3.9-kb region capable of
      rescuing men mutants blocked in the early stages of MK biosynthesis was sequenced
      and found to contain three major open reading frames (ORFs). The first ORF (menF)
      has a predicted size of 51.8 kDa and 34% amino-acid identity with the
      isochorismate synthases of Escherichia coli (EntC) and Aeromonas hydrophila
      (AmoA), ORF2 (menD) a predicted size of 60.2 kDa and 21% identity with MenD of E.
      coli. ORF3 has a predicted size of 21.4 kDa and 29% identity to triacylglycerol
      lipase of Psychrobacter immobilis. No sequence corresponding to menC was
      identified. Plasmid integrational studies of the men gene cluster had suggested
      the presence of promoters secondary to the previously identified p1 men promoter.
      Sequence analysis revealed a putative promoter region upstream from ORF3.

PMID- 8566761
TI  - Association of staphylococcal type-1 capsule-encoding genes with a discrete
      genetic element.
AB  - Previous studies have shown that 13 genes located in a 14.6-kb region of the
      chromosome of Staphylococcus aureus (Sa) M are required for type-1 capsular
      polysaccharide (CP1) biosynthesis. In this report, a total of 17 Sa strains
      producing different CP serotypes were analyzed by Southern hybridization using
      DNA probes from the cap1 coding region and the flanking sequences. The results
      showed that the sequence encoding cap1 genes was specific to CP1-producing
      strains. In addition, DNA regions of at least 18 kb flanking the cap1 genes were
      absent in most of the non-type-1 strains. These data suggest that the cap1 genes
      are associated with a chromosomally located discrete genetic element. One end of
      the element, referred to as the cap1 element, is located in a 1.7-kb fragment
      about 11.1 kb upstream from the first gene of the cap1 locus and the other end is
      located in a 0.8-kb region about 7.6 kb downstream from the last gene of the cap1
      locus. Thus, the size of the cap1 element is between 33.3 and 35.8 kb.

PMID- 8566760
TI  - Analysis of Staphylococcus aureus genes encoding penicillin-binding protein 4 and
      an ABC-type transporter.
AB  - A region of the Staphylococcus aureus chromosome has been isolated that contains
      the gene encoding penicillin-binding protein 4 (PBP4), as well as abcA, a gene
      that encodes a protein with strong sequence similarity to the ABC transporter
      family of proteins. A disruption in abcA by Campbell-type integration results in
      cells that display an increased resistance to methicillin and cefoxitin, two
      antibiotics known to interact with low-molecular-weight PBPs. Based on these
      observations, a potential regulatory link between these two genes is discussed.

PMID- 8566762
TI  - Analysis of two capreomycin-resistance determinants from Streptomyces capreolus
      and characterization of the action of their products.
AB  - Two genes encoding capreomycin (Cp)-modifying enzymes have been isolated from the
      producing organism Streptomyces capreolus. Cp acetyltransferase (CAC), encoded by
      cac, is active against all four components of the Cp complex, whereas Cp
      phosphotransferase (CPH), the product of cph, is active against Cp components IA
      and IIA (and also the related antibiotic, Vm) but not against Cp IB or Cp IIB.

PMID- 8566763
TI  - Cloning, expression and sequence analysis of the genes encoding the heterodimeric
      methylmalonyl-CoA mutase of Porphyromonas gingivalis W50.
AB  - Two genes that encode methylmalonyl-CoA mutase (MCM) have been characterised in
      Porphyromonas gingivalis W50 (Pg). The genes, designated mcmA and mcmB are
      transcribed in an operon and encode the MCM small subunit (SS, 68,626 Da) and the
      MCM large subunit (LS, 78,703 Da), respectively. A recombinant Escherichia coli
      (Ec) clone harbouring the Pg mcmA and mcmB genes expressed MCM activity 280-times
      higher than that of the Ec control. The C terminus of the MCM LS has sequence
      homology to domains of a variety of enzymes that consume or produce methylmalonyl
      CoA, suggesting that the MCM LS C-terminal domain is involved in substrate
      binding. The MCM LS C-terminal region also exhibits homology to other enzymes
      that have cobalamin-containing cofactors. It is likely, therefore, that the C
      terminus of the MCM LS is an important MCM domain involved in both substrate and
      cofactor binding.

PMID- 8566764
TI  - Identification of alcA, a Bordetella bronchiseptica gene necessary for alcaligin
      production.
AB  - The alcA gene, essential for the production of the dihydroxamate siderophore,
      alcaligin, by Bordetella bronchiseptica, was cloned and sequenced. The alcA gene
      was identified on a 4.7-kb EcoRI genomic fragment adjacent to a Tn5lac transposon
      insertion that inactivated alcaligin production in strain MBORD846. Analysis of
      the alcA nucleotide sequence revealed a putative Fur-binding site, suggesting
      that expression of this gene is repressed by iron. The deduced amino-acid
      sequence of this open reading frame had significant homology with the Escherichia
      coli iucD gene product, an enzyme required for biosynthesis of the dihydroxamate
      siderophore aerobactin.

PMID- 8566765
TI  - The recA gene of Borrelia burgdorferi.
AB  - The nucleotide sequence of the Borrelia burgdorferi (Bb) Sh-2-82 recA gene has
      been determined using PCR-based approaches without the construction of a genomic
      library. The gene should encode a protein of 365 amino acids which is highly
      homologous to other known RecA proteins. It represents a new homolog from a
      distinct phylogenetic branch of eubacteria. Although, previous reports concluded
      that recA is absent from Bb, the identification presented here conclusively shows
      its presence and reaffirms the ubiquity of RecA in prokaryotes.

PMID- 8566766
TI  - Direct linkage of str-, S10- and spc-related gene clusters in Thermus
      thermophilus HB8, and sequences of ribosomal proteins L4 and S10.
AB  - We have analyzed the genomic region harboring str-S10-spc-related gene clusters
      in the thermophilic bacterium, Thermus thermophilus (Tt) HB8. This study was
      initiated for the purpose of isolating the gene encoding ribosomal (r-) protein
      S10 which is assumed to be involved in the antitermination of transcription at
      the rRNA-encoding genes in Bacteria. The S10-related gene cluster encodes the
      same set of r-proteins as in Escherichia coli. However, the gene coding for
      elongation factor Tu (the last gene of the str operon in E. coli) is separated by
      only eight nucleotides (nt) from the gene encoding r-protein S10 (the first gene
      of the S10 operon in E. coli), and the genes encoding r-protein S17 (the last
      gene of the S10 operon in E. coli) and L14 (the first gene of the spc operon in
      E. coli) overlap. This suggests that all three gene clusters are cotranscribed
      from a single promoter preceding the str-related operon. In addition, we
      determined the complete nt sequences of the Tt genes encoding r-proteins L4 and
      S10. Tt L4 shows the lowest degree of conservation among the known L4 r-proteins
      from Bacteria. Tt S10 has the highest proportion of basic amino acids (aa) and
      the lowest number of acidic aa, as compared with its homologues from Bacteria and
      Archaea, which might be related to its possible role in binding to the boxA RNA
      of nascent rRNA transcripts at high temperatures.

PMID- 8566767
TI  - A putative SOS repair gene (dinF-like) in a hyperthermophilic archaeon.
AB  - The hyperthermophilic archaeon, Pyrococcus (strain IFREMER AL585), contains an
      ORF that encodes a polypeptide with a high similarity to the Escherichia coli
      dinF (DNA damage-inducible) gene product. The conservation of this protein
      between Archaea and Bacteria suggests that a SOS repair system might operate in
      Archaea.

PMID- 8566768
TI  - Analysis of second-site mutations that suppress the multiple drug resistance
      phenotype of the yeast PDR1-7 allele.
AB  - The yeast PDR1 locus encodes a member of the C6 zinc cluster family of
      transcriptional regulatory proteins. Among the targets of PDR1 is the yeast PDR5
      locus. The product of this gene is a member of the ATP-binding cassette (ABC)
      transmembrane protein family and plays a major role in inhibitor efflux.
      Mutations in PDR1 affect the relative level of PDR5 transcript and can therefore
      result in increased or decreased drug resistance. We isolated three second-site
      suppressors of a PDR1-7 semidominant hyper-resistant mutation. These mutants were
      drug hypersensitive, as compared with isogenic controls. Two of the three
      mutations contained alterations in a putative DNA-binding domain. Significantly,
      the mutant proteins exhibited reduced DNA-binding capacity.

PMID- 8566769
TI  - Cloning and characterization of the POX2 gene in Candida maltosa.
AB  - To study the function of acyl-CoA oxidase in an n-alkane-assimilating yeast,
      Candida maltosa, we isolated the POX2 gene which is a member of the acyl-CoA
      oxidase gene family. POX2 had a 2172-bp open reading frame (ORF) encoding an
      approx. 84-kDa polypeptide (724 amino acids (aa)) and was contiguous to POX4,
      another member of the acyl-CoA oxidase gene family on the same chromosomal DNA in
      a convergent arrangement. Northern blot analysis revealed that the expression of
      POX2 was induced in cells grown on oleic acid, n-tetradecanol and n-tetradecane.
      By using a gene-disruption technique, we constructed strains (termed P2DD and
      P4DD) in which both alleles of POX2 and POX4 were disrupted. The P2DD strain was
      normal in assimilation of various hydrophobic carbon sources, such as n
      tetradecane, n-tetradecanol and oleic acid. In contrast, the P4DD strain was
      defective in its ability to grow on such hydrophobic carbon sources.

PMID- 8566770
TI  - Cloning and characterization of the mitochondrial HSP60-encoding gene of
      Schizosaccharomyces pombe.
AB  - We report the isolation and characterization of a gene (designated mcp60)
      encoding the mitochondrial (mt) 60-kDa heat-shock protein (HSP60) in the fission
      yeast Schizosaccharomyces pombe. The deduced amino-acid sequence (582 aa) of this
      gene is highly similar to the known mt HSP60 from diverse organisms. When its
      sequence was related to the known functional domains of bacterial HSP60 (GroEL),
      the similarity was particularly high for the intermediate domains that connect
      the apical domain with the equatorial domain. The mRNA level of mcp60 increased
      several-fold upon temperature upshift (from 25 to 35 degrees C), while gradually
      decreased during sporulation. Gene disruption experiments revealed that mcp60 is
      essential for cell viability at all temperatures.

PMID- 8566771
TI  - Cloning, structural organization and regulation of expression of the Penicillium
      chrysogenum paf gene encoding an abundantly secreted protein with antifungal
      activity.
AB  - An abundantly secreted, highly basic 12-kDa protein (PAF) was purified from the
      culture medium of Penicillium chrysogenum (Pc). Based on the N-terminal amino
      acid (aa) sequence of the protein, an oligodeoxyribonucleotide probe was derived
      and used for amplification of the encoding cDNA by PCR. This cDNA fragment
      encodes a Cys-rich preproprotein of 92 aa which appears to be processed to a
      mature product of 55 aa. The deduced aa sequence of the preproprotein reveals
      42.6% identity to an antifungal protein (AFP) of Aspergillus giganteus. Agar
      diffusion tests confirmed that the Pc protein exhibits antifungal activity. In
      order to investigate the promoter region and the structural organization of the
      paf gene, a genomic 6-kb fragment was isolated and partially sequenced.
      Comparison of the nucleotide sequence of the genomic fragment and the cDNA clone
      revealed the presence of a coding region of 279 bp which is interrupted by two
      introns of 76 and 68 bp in length. In the promoter region, a typical TATA box, a
      motif resembling the fungal carbon catabolite repression element, as well as
      several putative GATA factor binding motifs, were found. Northern blot analysis
      indicated that the regulation of paf expression occurs at the level of mRNA
      transcription and is under control of carbon catabolite and nitrogen metabolite
      repression regulatory circuits.

PMID- 8566772
TI  - Characterization of two members (ACS1 and ACS3) of the 1-aminocyclopropane-1
      carboxylate synthase gene family of Arabidopsis thaliana.
AB  - The nucleotide sequences of two highly homologous 1-aminocyclopropane-1
      carboxylate (ACC) synthase (ACS; EC 4.4.1.14)-encoding genes, ACS1 and ACS3, of
      Arabidopsis thaliana (At) have been determined. The sequence analysis shows that
      ACS3 is a pseudogene representing a truncated version of ACS1. The missing region
      of ACS3 corresponding to the fourth exon of ACS1 has been shown by Southern
      analysis to be absent in the At genome. The chromosomal locations of the five
      members of the At ACS multigene family have been determined. The results show
      that each family member resides on a different chromosome. This observation
      suggests that the ACS3 pseudogene originated by a partial inter-chromosomal gene
      duplication. The ACS1 polypeptide contains all the conserved and characteristic
      domains found in the ACC synthase isoenzymes from various plant species, but is
      unable to express ACS activity in Escherichia coli and yeast. The predicted amino
      acid sequence of ACS1 is missing the highly conserved tripeptide, Thr-Asn-Pro
      (TNP), between Ile204 and Ser205. Introduction of TNP into ACS1 restores the ACS
      activity, whereas its removal from the enzymatically active ACS2 results in a
      loss of activity. The results suggest that TNP is crucial for expression of ACS
      activity in E. coli.

PMID- 8566773
TI  - Isolation and characterization of two chitinase-encoding genes (cts1, cts2) from
      the fungus Coccidioides immitis.
AB  - Two chitinase (CTS)-encoding genes (cts) from Coccidioides immitis (Ci), a
      respiratory fungal pathogen of humans, were cloned and sequenced. Both the
      genomic and cDNA sequences are presented. The transcription start points and
      poly(A)-addition sites were confirmed. The cts1 gene contains five introns and a
      1281-bp ORF which translates a 427-amino-acid (aa) protein of 47.4 kDa. The cts2
      gene contains two introns and a 2580-bp ORF which translates a 860-aa protein of
      91.4 kDa. The deduced CTS1 protein showed highest homology to the Aphanocladium
      album and Trichoderma harzianum CTS (74% and 76%, respectively), while CTS2
      showed highest homology to the CTS of Saccharomyces cerevisiae (Sc) and Candida
      albicans (47% and 51%, respectively). The putative N-terminal sequence of the
      mature CTS1 protein also showed 89% homology to the reported N-terminal sequence
      of a 48-kDa complement fixation antigen (CF-Ag) of Ci which has demonstrated
      chitinase activity. The CF-Ag is a clinically important antigen used in
      serodiagnosis of this fungal disease. CTS2 showed several of the conserved
      features of the Sc CTS, including putative catalytic and Ser/Thr-rich domains,
      and a C-terminal Cys-rich region. We propose that CTS1 and CTS2 of Ci are members
      of two distinct classes of fungal chitinases, an observation not previously
      reported for a single fungus.

PMID- 8566774
TI  - Further analysis of the CAP59 locus of Cryptococcus neoformans: structure defined
      by forced expression and description of a new ribosomal protein-encoding gene.
AB  - Cryptococcus neoformans (Cn) produces an extracellular polysaccharide capsule
      that is an essential factor for virulence. We previously isolated a gene, CAP59,
      which is necessary for capsule formation. To dissect the functional region of
      CAP59, we placed it under control of the Cn GAL7 promoter (pGAL7). Among the
      several pGAL7::CAP59 fusion constructs, only the one containing the entire open
      reading frame of CAP59 was able to complement the acapsular phenotype under
      galactose induction. A missense mutation in the coding region abolished
      complementation by the fusion construct. We also found that the CAP59 locus is
      contiguous to a convergently transcribed L27 ribosomal protein-encoding gene
      (CL27). The distance between the cDNA ends of these two genes is only 25 bp. CL27
      has two introns near its N terminus. The translated CL27 protein is 183 amino
      acids (aa) in length with an estimated molecular mass of 20 kDa, and the first 34
      aa at the N terminus may be a targeting peptide for mitochondria. A high degree
      of restriction-fragment-length polymorphism was detected in the DNA sequence
      containing CAP59 and CL27.

PMID- 8566775
TI  - Cloning and characterization of a conserved region of human and rhesus macaque
      Pneumocystis carinii gpA.
AB  - Although the genes encoding Pneumocystis carinii (Pc) glycoprotein A (gpA)
      display a high degree of host species-specific genotypic diversity, the Pc gpA
      derived from different host species share defined regions of significant homology
      in their primary amino acid (aa) structure. Using two degenerate
      oligodeoxyribonucleotide (oligo) primers corresponding to a conserved Cys region
      (Cys-primers) of the ferret (F), rat (R) and mouse (M) PcgpA, a 306-bp portion of
      the human (H) PcgpA was amplified from only one of three known HPc-infected lung
      samples using PCR. The deduced aa sequence of the HPc PCR product was 72% similar
      to the corresponding region of a published HPc gpA aa sequence. Because the
      conserved Cys-primers amplified only one of three samples of HPcgpA, a primer
      pair was designed from sequences internal to the Cys-primer sequences of the
      HPcgpA PCR product (hPc). The hPc primers amplified the expected 254-bp product
      from each of the three HPc-infected lung DNA samples, suggesting that the Cys
      primers may have either amplified a HPcgpA present in fewer copies in the genome
      of HPc or, alternatively, amplified a gene from an uncommon strain of Pc encoding
      an isoform variant of gpA not present in the other human isolates analyzed in
      this report. Restriction analysis of the amplified products demonstrated
      heterogeneity in the internal sequence, confirming that more than one gpA exists
      in HPc as well. To determine the relationship of HPcgpA to the gpA of Pc from
      another primate, the hPc primers were used successfully to amplify a 261-bp
      product from Pc-infected Rhesus macaque (Rm) lung genomic DNA. These results are
      consistent with our earlier findings that closely related host species are
      infected with Pc organisms encoding similar gpA, suggesting that the evolutionary
      divergence of Pc followed that of the mammalian host species.

PMID- 8566776
TI  - Cloning of a ras-related gene from Hydra which responds to head-specific signals.
AB  - Members of the Ras family of proteins are important components of signal
      transduction pathways responding to external signals and leading to changes in
      cell behavior. Analysis of two ras-related genes in the phylogenetically old
      metazoan Hydra indicates that in normal animals both genes are expressed in all
      body regions of the polyp. Upon head removal, however, the transcript level of
      one of the two genes, ras2, decreases rapidly in the upper gastric region which
      is adjacent to the former head. The decrease is transient and specific for ras2,
      since no changes could be observed in the transcript level of the related ras1
      gene or any other gene. The disappearance of the ras2 mRNA can be prevented
      completely by brief exposure of decapitated polyps to the protein kinase C
      activator TPA, which previously was shown to be capable of converting gastric
      tissue into head tissue [Muller, W.A. In: Othmer, H.G. (Ed.) Experimental and
      Theoretical Advances in Biological Pattern Formation. Plenum Press, New York, NY,
      1993, pp. 237-253]. The finding that Hydra ras2 expression is strongly dependent
      on a signal from the head provides the first evidence for ras expression being
      regulated in pattern formation.

PMID- 8566777
TI  - Isolation and characterization of a cDNA encoding Arabidopsis thaliana 3-hydroxy
      3-methylglutaryl-coenzyme A synthase.
AB  - An 1.7-kb Arabidopsis thaliana (At) cDNA was isolated by complementation of a
      bap1 mutation affecting the transport of branched-chain amino acids (aa) in the
      yeast Saccharomyces cerevisiae. The determination of the nucleotide (nt) sequence
      revealed an open reading frame of 1383 nt which may encode a protein of 461 aa
      with a predicted molecular mass of 51,038 Da. The deduced aa sequence exhibited
      strong similarities with mammalian 3-hydroxy-3-methylglutaryl-coenzyme A synthase
      (HMGS) sequences. Although former biochemical studies have suggested that
      acetoacetyl-coenzyme A thiolase (AACT) and HMGS activities were carried by a
      single protein in plants, complementation studies and measurements of enzymatic
      activities clearly showed that the At HMGS is devoid of AACT activity.

PMID- 8566779
TI  - Cloning and characterization of a Brassica napus gene encoding a homologue of the
      B subunit of a heteromeric CCAAT-binding factor.
AB  - The CCAAT motif present in the promoter of several genes is recognized in yeast
      and animals by a highly specific heteromeric factor (variously called HAP, CBF,
      CP1 or NF-Y) which is composed of a minimum of three subunits. A plant homologue
      of the CBF-B/HAP2 subunit is described for the first time in this report.
      Sequence comparison of the Brassica napus (Bn) CCAAT-binding factor (CBF) B
      subunit with the homologous yeast and animal proteins revealed that the critical
      amino-acid domains involved in DNA binding and subunit assembly are also
      conserved in plants. Interestingly, the Gln-rich regions found in the animal and
      yeast proteins, which may be involved in transcriptional activation, are absent
      in the Bn CBF-B subunit. The analysis of various cDNAs and of a genomic clone
      revealed the presence of alternatively spliced transcripts which could originate
      from different promoters.

PMID- 8566780
TI  - High-level production of spinach glycolate oxidase in the methylotrophic yeast
      Pichia pastoris: engineering a biocatalyst.
AB  - Glycolate oxidase (GO) is a flavo-enzyme that catalyzes the oxidation of
      glycolate, and is useful for the biocatalytic production of glyoxylate. We have
      produced high levels of spinach GO in the methylotrophic yeast Pichia pastoris
      (Pp), by chromosomal integration of multiple copies of an expression cassette
      containing the GO coding sequence under control of the methanol-inducible alcohol
      oxidase I promoter. Under fermentation conditions, greater than 250 units of GO
      per gram of cells (wet weight) was obtained, corresponding to roughly 20-30% of
      soluble cell protein. This recombinant Pp strain was used as a whole-cell
      biocatalyst for conversion of glycolic acid to glyoxylic acid.

PMID- 8566778
TI  - Arabidopsis expresses two genes that encode polypeptides similar to the yeast RNA
      polymerase I and III AC40 subunit.
AB  - A 40-kDa subunit in eukaryotic RNA polymerases (Pol) I and III (e.g., yeast
      yAC40) is related in a part of its aa sequence to the alpha subunit of
      prokaryotic Pol and to a 35-44-kDa subunit in Pol II (e.g., yeast yB44). We have
      cloned two cDNAs, AtRPAC42 and AtRPAC43, from an Arabidopsis thaliana (At)
      (ecotype Columbia) lambda Yes expression library that encode Pol I and III
      subunits related to yAC40. The aa sequences derived from the cDNA clones were
      found to be 72% identical to each other and 40% identical to yeast Pol I and III
      subunits yAC40, but only 30% identical to yeast Pol II subunit yB44. While most
      other nuclear Pol genes identified to date are single-copy genes, two genes
      encode 42 and 43-kDa subunits of At Pol I and/or III. A 42-kDa subunit with
      identical mobility in SDS-PAGE to the aAC42 in vitro translated subunit is found
      in Pol III purified from At suspension culture cells.

PMID- 8566781
TI  - Similar cleavage efficiencies of an oligoribonucleotide substrate and an mdr1
      mRNA segment by a hammerhead ribozyme.
AB  - Hammerhead ribozymes (Rz) can specifically recognize and cleave target RNAs in
      trans. This makes them attractive in antisense RNA approaches for specific gene
      inactivation in vivo. A severe limitation is the poor cleavage efficiency of
      large RNA substrates, in contrast to the high activities observed with small
      oligoribonucleotides (oligos) as model substrates. It was suggested that the low
      efficiency is caused by poor accessibility of the target sequence in the
      structure of the long RNA substrates. This means it should be possible to
      overcome this limitation by judicious choice of the target sequence, although
      experimental proof was lacking. We observed similar cleavage efficiencies of
      small and large RNA substrates with a hammerhead Rz directed against multidrug
      resistance-encoding mdr1 mRNA. Accordingly, large RNAs can also be good
      substrates, if an optimal target sequence is selected.

PMID- 8566782
TI  - The Caenorhabditis elegans rop-1 gene encodes the homologue of the human 60-kDa
      Ro autoantigen.
AB  - As a first step toward establishing a genetic system for the elucidation of the
      cellular role(s) of the Ro ribonucleoproteins (RoRNP), we have cloned the gene
      encoding the homologue of the human 60-kDa Ro protein (Ro60) in Caenorhabditis
      elegans (Ce). This Ce gene is present as a single copy and contains a 643-codon
      open reading frame interrupted by three introns. The encoded protein, Rop1p,
      shares 40% identity and 63% overall similarity with both the human and amphibian
      Ro60. Recombinant protein has been produced in Escherichia coli and used to
      elicit anti-Rop1p antibodies. Immunological analysis indicated that the Ro60
      epitopes have been poorly conserved. Gene-fusion expression studies in transgenic
      nematodes will provide a new avenue of research to shed light on the function of
      these particles.

PMID- 8566783
TI  - Cloning of cDNA and genomic structure of the mouse gamma-glutamyl transpeptidase
      encoding gene.
AB  - We have isolated and characterized cDNA and genomic clones containing the coding
      region for the mouse gamma-glutamyl transpeptidase (GGT). The sequences of the
      full-length cDNAs for three of the seven known mouse Ggt RNAs (types I, II and
      III) were determined and found to be identical in the coding region. Comparisons
      of the deduced amino-acid sequence of mouse GGT with that of rat and human reveal
      95 and 79% overall identities, respectively. The mouse Ggt gene has 12 coding
      exon and spans approx. 12 kb. We have also re-analyzed rat genomic Ggt clones
      previously isolated by us and found that the rat and mouse genes share the same
      intron/exon boundaries. Our findings are of interest because they define the
      structure of the mouse and rat Ggt genes and will allow comparison with human GGT
      genes which, recent findings suggest, have diverged substantially from rodents.

PMID- 8566784
TI  - Repression of promoters for the mouse insulin-like growth factor II-encoding gene
      (Igf-2) by products of the Wilms' tumour suppressor gene wt1.
AB  - We have investigated actions of the Wilms' tumour suppressor zinc finger
      transcription factor, WT1, on promoters of the mouse insulin-like growth factor
      II-encoding gene (Igf-2). Two variant forms of WT1 repressed the two major Igf-2
      promoters (P2 and P3) in transient transfection assays. WT1-binding sites were
      characterised in both these promoters and in the transcribed region downstream
      from P2, exon 2. In each of these regions, there was a pair of WT1-binding sites,
      and mutational analysis of the exon-2 sites indicated that both were required for
      full repression. Cooperative binding of WT1 to these sites might explain the
      dominant-negative mutations of WT1 observed in some Wilms' tumours and Denys
      Drash syndrome cases.

PMID- 8566785
TI  - Inverted repeats are necessary for circularization of the mouse testis Sry
      transcript.
AB  - Circular non-polyadenylated RNA molecules have been identified as stable
      transcription products of the human ETS-1 and mouse Sry genes. RNA
      circularization has been proposed to require two steps. The first step utilizes
      intramolecular base pairing to produce a transient stem-loop structure. The
      second step involves splicing a downstream donor splice site (DSS) to a now
      closely appositioned upstream acceptor splice site (ASS) within the loop. We
      demonstrate that the presence of long inverted repeats (IR) flanking the mouse
      Sry gene leads to the formation of the Sry circular transcript in cultured cells.
      Circularization requires the presence of both IR. As few as 400 complementary nt
      are necessary for this process. The presence of the IR does not significantly
      stimulate intermolecular annealing and trans-splicing in vivo.

PMID- 8566786
TI  - Isolation and characterization of the gene coding for murine high-mobility-group
      protein HMGI-C.
AB  - The HMGI-C protein is a nuclear factor expressed in human and rodent neoplastic
      cells which has been shown to be involved in the process of cell transformation.
      We have previously isolated the cDNA encoding murine HMGI-C and now we report the
      cloning and analysis of the mouse Hmgi-c gene. The gene is at least 50 kb long,
      contains five exons, and each of the three DNA-binding domains is encoded by a
      different exon. The location of exon-intron junctions was determined and shown to
      follow the GT-AG rule. The sequence revealed that the overall organization is
      similar to the gene encoding human HMGI(Y), the other member of the HMGI family,
      suggesting that HMGI genes probably evolved through gene duplication and exon
      shuffling events from an ancestral gene. A highly homologous pseudogene is also
      present in the mouse genome. Our results on Hmgi-c structure provide basic
      information to carry out further studies on the regulation of its expression.

PMID- 8566787
TI  - Cloning of the mouse gene encoding plasma glutathione peroxidase: organization,
      sequence and chromosomal localization.
AB  - Using a reverse transcription coupled to PCR amplification strategy, with
      degenerated primers localized in highly conserved domains of known glutathione
      peroxidase (GPX) proteins, we have generated, from mouse epididymal RNA, a cDNA
      fragment which was subsequently used to isolate a genomic clone encoding mouse
      plasma GPX (GPX3). GPX3 is a major enzyme in reducing lipid hydroperoxides and
      hydrogen peroxide in plasma. We confirm here that the mouse epididymis is a new
      site of expression of GPX3 and report, together with the sequence, the structural
      analysis and the chromosomal localization of the mouse GPX3 single-copy gene to
      chromosome 11.

PMID- 8566788
TI  - Identification of three transcriptional regulatory elements in the rat
      mitochondrial benzodiazepine receptor-encoding gene.
AB  - The sequence upstream from the first exon in the rat mitochondrial benzodiazepine
      receptor-encoding gene (MBR) was analyzed for transcriptional promoter activity
      by three techniques: promoter deletion analysis in vectors containing the gene
      cat encoding chloramphenicol acetyltransferase, electrophoretic mobility shift
      analysis (EMSA) and DNase I protection assay. All three methods are in uniformity
      with the identification of at least three regulatory elements corresponding to
      locations -51/-33, -267/-249 and -555/-526. The most distal and proximal domains
      are positive-acting, whereas the element at -267/-249 acts in a negative manner.
      The positive-acting -51/-33 element contains the middle of three consensus Sp1
      recognition sequences found in this region of the gene. Binding of Y1 cell
      nuclear protein to a DNA fragment corresponding to this region of the gene is
      competed by a synthetic oligodeoxyribonucleotide bearing the consensus Sp1
      binding site sequence. These studies provide the first reported functional
      evidence localizing transcriptional elements of MBR.

PMID- 8566789
TI  - Identification of a murine homolog of the human adenosine deaminase thymic
      enhancer.
AB  - We have identified a 236-bp first intron segment of the mouse adenosine deaminase
      gene (ADA) that shares 71.1% identity with the human ADA thymic enhancer. This
      segment has the same natural orientation as the human enhancer and a relative
      location within the first intron very analogous to that of the human enhancer.
      Four highly conserved regions were defined within this segment, including a 72-bp
      region having 83.6% identity with a segment containing the critical human
      enhancer core. Several consensus binding sequences were also conserved within
      these regions. Transient transfection assays in human and murine T-cell lines
      revealed that a 1.8-kb murine genomic fragment harboring the 236-bp segment
      functions as a weak activator of both the human and mouse ADA promoters. In
      contrast, a 2.3-kb human enhancer fragment exhibited high-level activation in
      conjunction with either the human or mouse ADA promoter in both the MOLT 4
      (human) and S49 (murine) T-cell lines. Interestingly, the murine ADA promoter is
      significantly stronger than the human promoter in driving cat expression in
      transient transfection assays in all the T-cell lines tested.

PMID- 8566790
TI  - Transcription of the rat liver uricase-encoding gene is regulated via a cis
      acting element responsive to cAMP.
AB  - Glucagon was found to increase the mRNA level of the uricase-encoding gene (UOX),
      but not that of genes encoding other peroxisomal enzymes, such as catalase, acyl
      CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase. The possible
      involvement of cAMP in the glucagon-induced transcription of rat UOX was studied
      by measuring the enhancer activity of the isolated 5'-untranslated region of the
      gene. An 84-bp sequence spanning positions -169 to -86 was found to be essential
      for cAMP-mediated expression of rat UOX, on deletional analysis of the upstream
      1.4-kb portion by means of a transient transfection assay (CAT assay). The 30-mer
      oligodeoxyribonucleotide (positions from -169 to -140) was found to form a DNA
      protein complex by an electrophoretic mobility shift assay. The core sequence for
      the DNA-protein complex formation, 5'-CAAAAATGTC-3', was found to be located in
      positions from -164 to -155. In addition, the binding assays suggested that the
      DNA-binding protein(s) was different from cAMP-response element binding protein
      (CREB). Thus, this report shows that a novel cis-acting element of rat UOX and
      the binding protein(s) possibly play an essential role in the glucagon-induced
      transcription via cAMP.

PMID- 8566791
TI  - Cloning and characterization of a lung-specific cDNA corresponding to the gamma
      chain of hepatic fibrinogen.
AB  - The gene (gamma FBG) encoding the fibrinogen gamma chain (gamma FBG) has been
      shown to exhibit both tissue-specific and ubiquitous expression. To confirm the
      identity of the gamma FBG transcripts expressed in extrahepatic tissue, lung
      tissue was chosen as a model of extrahepatic gamma FBG gene expression. A ferret
      lung cDNA clone bank was constructed in lambda gt11 and several positive plaques
      were isolated using cross-species hybridization with the rat gamma FBG cDNA.
      Sequence data of the longest clone, designated pFLG gamma 3, was compared at the
      nucleotide and deduced amino acid (aa) levels with sequences of gamma FBG from
      other species. The results indicated that the identity of the ferret lung
      specific gamma FBG cDNA to pig, rat, bovine and human gamma FBG cDNAs ranged from
      78-88%; the similarity of the ferret lung-specific gamma FBG deduced aa sequence
      ranged from 84-88% across species. Cysteine aa involved in intra- and inter-chain
      disulfide-bonded secondary and tertiary structure are absolutely conserved in
      ferret gamma FBG. The putative cell-cell adhesion sites for both platelet alpha
      IIb beta 3 and intercellular adhesion molecule-1 receptor binding to ferret gamma
      FBG are > 90% similar to the corresponding sites in the human gamma FBG. The
      results of Northern hybridization indicated that the ferret lung gamma FBG mRNA
      was equivalent in size to the liver gamma FBG mRNA; Southern hybridization
      suggested that ferret gamma FBG is a single-copy gene, as is the gamma FBG of
      other species. Lung-specific gamma FBG expression was localized to epithelial
      cells of the large and small airways and chondrocytes by in situ RNA:RNA
      hybridization. The functional significance of gamma FBG expression in lung is not
      presently known. Since expression of FBG is up-regulated 2-10-fold in the liver
      during an inflammatory event, it is possible that lung-specific gamma FBG
      expression occurs predominantly during lung disease or injury.

PMID- 8566792
TI  - A single amino-acid change between the antigenically different extracellular
      serine proteases V2 and B2 from Dichelobacter nodosus.
AB  - Dichelobacter nodosus (Dn), the causative organism of ovine footrot, secrets
      three distinct types of extracellular serine proteases which have been implicated
      in virulence. Southern analyses have shown that the proteases are encoded by
      three separate genes, and the genes encoding an acidic protease V5 and a basic
      protease have already been characterised from virulent Dn strain 198. The gene
      encoding the third protease type, as represented by acidic protease V2, was
      isolated from an EcoRI-BamHI library of strain 198 genomic DNA by probing with a
      polymerase chain reaction (PCR) fragment generated with oligodeoxyribonucleotides
      based on protease V2 amino acid (aa) sequences. A further clone from an RsaI
      library was isolated to complete the 5' region of the gene to yield an ORF of
      1803 bp encoding a protein precursor of 601 aa. The acidic protease V2 gene,
      aprV2, shows the same precursor structure as the bprV and aprV5 genes with 72%
      and 69% similarity at the nucleotide (nt) level and with 73% and 69% similarity
      at the aa level, respectively. As monoclonal antibodies consistently distinguish
      the virulent (V) and benign (B) forms of this protease, the gene encoding the
      acidic protease B2 from benign Dn strain 305 was isolated using the PCR and
      characterized to investigate the molecular basis for this difference in
      antigenicity. A 2-bp substitution in a single codon was identified which appeared
      to be responsible for a change of epitope.

PMID- 8566793
TI  - PCR strategies for isolation of the 5' end of an immunoglobulin-encoding bovine
      cDNA.
AB  - We have employed two in vitro amplification strategies in our attempts to
      characterise the variable region of bovine immunoglobulin heavy chains (VH).
      Products derived by 5' RACE (rapid amplification of cDNA ends) spanned the coding
      sequence, but diversity in the complementarity determining regions was highly
      restricted, indicating that a limited subset of the heavy-chain repertoire had
      been recovered. In contrast, unique, full-length VH determinants were obtained
      with ease by an inverse application of the polymerase chain reaction. The
      strength of this approach is considerable: it is straightforward to perform,
      requiring none of the tailing procedures inherent to RACE strategies, yet it
      enables the rapid isolation of uncharacterized regions of genes for which limited
      sequence data are available. Our findings suggest strongly that the heavy-chain
      repertoire of cattle is highly dependent upon a very limited number of germline
      VH and JH (joining region) gene families.

PMID- 8566794
TI  - Comparison of the 5'-flanking sequences of the human and bovine von Willebrand
      factor-encoding genes reveals alternation of highly homologous domains with
      species-specific Alu-type repeats.
AB  - von Willebrand factor (vWF), a multimeric glycoprotein important for hemostasis,
      is specifically synthesized in endothelial cells and in platelet precursors
      (megakaryocytes). Recent studies from two laboratories, including ours, were
      published regarding the cell-specific transcription of reporter genes controlled
      by the human (hu) vWF promoter in transfected bovine (bo) endothelial cells and
      cells of non-endothelial origins. In order to verify that the regulatory domains
      previously characterized in the 5' region of hu vWF are also present in bo vWF,
      we have sequenced 1.9 kb upstream from the cap site, plus five exons. The
      comparison of human and bovine exons two to five shows homology of 83% at the
      nucleotide (nt) level and 78% at the deduced amino-acid sequence level. The
      bovine and human exons one, which are non-coding and span 233 and 250 bp,
      respectively, are only 64% homologous. In the first exon, potentially involved in
      endothelial-cell-specific transcription, the binding site for factor Sp1 is
      present in bo vWF, whereas the GATA sequence is replaced by a GACA sequence. The
      sequence corresponding to the human basal promoter, located between nt -89 and
      +19, is well conserved with 82% homology. However, the human TAATTA sequence (at
      nt -32) considered to be a TATA box, is replaced by TCATTA, and the CCAAT element
      at nt -18 is replaced by CCTGT. Among domains involved in transcription, the
      negative regulatory domain located 5' from the core promoter is highly conserved.
      The bovine sequence upstream from the first intron can be aligned with the human
      sequence up to nt -656 which is located in a polymorphic poly(GT)18-26 sequence.
      At this site, the bovine DNA contains an insertion of 523 bp which corresponds to
      a bovine Alu-type art2 repeat of 331 bp flanked by bovine microsatellites. The
      art2 sequence is an Alu-type repeat in artiodactyls with at least 100,000 copies
      in the bovine genome. Upstream from this insertion, 368 bp of the bovine sequence
      can be aligned with the human counterpart up to a 9-bp element which flanks an
      human Alu repeat which is absent from the bovine DNA. Upstream of the human Alu
      insertion and a duplicate of the 9-bp element, the two sequences are again
      homologous.

PMID- 8566795
TI  - Isolation and characterization of a cDNA encoding a new type of human
      transcription elongation factor S-II.
AB  - We report the isolation of a cDNA encoding a new type of transcription factor S
      II, termed h-SII-T1, from a human library. The mRNA corresponding to the clone is
      highly expressed in testis and ovary. Comparison of the deduced amino acid (aa)
      sequence with those of other S-II molecules shows that (i) the C-terminal zinc
      finger (Zf) domain is highly conserved, and (ii) the central segment is most
      similar to that of the rat testis-specific S-II. Further analyses of the hS-II-T1
      aa sequence indicate that its N-terminal sequence exhibits similarity to
      eubacterial sigma 54. The significance of tissue-specific S-II molecules for the
      regulation of transcription elongation is discussed.

PMID- 8566796
TI  - Cloning and characterization of a member of the MST subfamily of Ste20-like
      kinases.
AB  - We have identified a second human homology of the yeast Ste20 protein kinase
      family, which we designate MST2. MST2 is most similar to the previously
      identified MST1 protein kinase (78% identity, 88% similarity). Northern analysis
      indicates that MST2 mRNA is expressed at high levels in adult kidney, skeletal
      and placental tissues and at very low levels in adult heart, lung, liver and
      brain tissues. An in vitro kinase assay indicates that MST2 can phosphorylate an
      exogenous substrate, as well as itself, and phospho-amino-acid analysis indicates
      that it is a serine/threonine protein kinase. The identification of MST2 suggests
      that there may be subfamilies of Ste20-like protein kinases and that MST1 and
      MST2 may define one of these subfamilies.

PMID- 8566797
TI  - Isolation and characterization of the promoter of the human 5'-nucleotidase
      (CD73)-encoding gene.
AB  - Ecto-5'-nucleotidase (NT, CD73) is a purine salvage-pathway enzyme located on the
      surface of various cell types, including subsets of human lymphocytes and certain
      leukemias and lymphomas. In addition to purine salvage, NT has proposed roles in
      lymphocyte maturation and activation, and its expression has been associated with
      the resistance of some tumor cell lines to chemotherapeutic agents. To better
      understand the regulation of NT gene expression in normal lymphocyte development
      and the elevated expression seen in some drug-resistant tumor cell lines, we
      isolated NT genomic clones containing the promoter region. The genomic DNA
      upstream from the NT start codon is high in G+C content, with one cAMP-responsive
      element and five consensus Sp-1 binding sites, but no TATAA box. RNase protection
      assays identified a cluster of potential transcription start points (tsp). One
      tsp, at -63 bp relative to the start codon, was confirmed as authentic by 5'-RACE
      (rapid amplification of cDNA ends) cloning. Transient transfection experiments
      utilizing luc as a reporter gene have demonstrated that a 155-bp NT genomic DNA
      segment inclusive of the tsp functions as a promoter in both NT+ (WI-L2 and MG)
      and NT- (Jurkat, Hela and Raji) cell lines. The addition of 5'-flanking sequences
      extending as far as -1.9 kb did not confer cell-type-specific expression to the
      core promoter. However, nuclear run-on analysis of nascent NT transcripts
      suggested that differential transcription initiation is at least partially
      responsible for the regulation of NT expression. Thus, additional information is
      necessary, either at the chromatin level, or within elements outside of the
      promoter region, to direct tissue-specific expression of NT.

PMID- 8566798
TI  - Genomic organisation and chromosomal localisation of the gene encoding human beta
      adducin.
AB  - Adducin (ADD) is a heterodimeric protein of the membrane skeleton with subunits
      of 103 (alpha) and 97 kDa (beta). It promotes the assembly of the spectrin-actin
      network. We have previously shown that one point mutation in each of the alpha
      and beta rat ADD-encoding genes is associated with blood pressure variation in an
      animal model for hypertension, the Milan hypertensive strain of rats, probably
      due to a change in the phosphorylation pattern. In fact, the rat mutations, Y to
      F for alpha and R to Q for beta, are located, respectively, in a tyrosine kinase
      and a protein kinase A phosphorylation site. We have now determined, for the
      human beta-ADD-encoding gene, its chromosomal localisation, exon-intron
      organisation and alternative splicing patterns. We report here that human beta
      ADD is localised on chromosome 2 and we also show a characteristic 3' end
      alternative splicing of the beta-ADD RNA that generates two distinct beta-ADD
      families, namely ADD 63 and 97; both of them in turn present a very complex
      differential splicing pattern in the internal exons.

PMID- 8566799
TI  - Sequence analysis of the 5.34-kb 5' flanking region of the human rhodopsin
      encoding gene.
AB  - In order to define elements which may be involved in regulating human rhodopsin
      expression, we have isolated and sequenced a clone containing 5.34 kb of the 5'
      upstream region of the human rhodopsin-encoding gene. The 5.34-kb human segment
      contains multiple potential transcription factor-binding sites and a subfamily of
      Alu repeats. The same subfamily of Alu repeats is found 5.8 kb upstream from the
      human red/green visual pigment-encoding gene.

PMID- 8566800
TI  - Isolation and characterization of the 5'-flanking sequence of the human ocular
      lens MIP gene.
AB  - The MIP (major intrinsic protein) gene, a member of an ancient family of membrane
      channel genes, encodes the predominant fiber cell membrane protein of the ocular
      lens. Its specific expression in the lens fibers is temporally and spatially
      regulated during development. To study the regulation of expression of MIP and
      delineate the regulatory elements underlying its tissue specificity and ontogenic
      profile, we have cloned 2840 bp of the human MIP 5'-flanking sequence. The human
      MIP 5'-flanking sequence contains three complete Alu repetitive elements in
      tandem at position between nt -1699 and -2684 (nt -1699/-2684). These Alu
      elements appear to have had a complex evolutionary history with insertions at
      different times. We have fused DNA fragments containing MIP 5'-flanking sequences
      to the bacterial cat reporter gene encoding chloramphenicol acetyltransferase and
      assayed them in primary cultures of chicken lens cells. We have mapped two
      negative regulatory regions in the human MIP 5'-flanking sequences -1564/-1696
      and -948/-1000. We demonstrated that the human MIP 5'-flanking sequence -253/+42
      contains a functional promoter in lens cells but is inactive in kidney epithelial
      cells or mouse fibroblasts, suggesting that this sequence contains regulatory
      elements responsible for the lens-specific expression of MIP.

PMID- 8566801
TI  - Sex identification of archaeological human remains based on amplification of the
      X and Y amelogenin alleles.
AB  - Sex identification of archaeological human remains is essential for the
      exploration of gender differences in past populations. Traditional morphometric
      analyses fail to identify the gender of incomplete skeletal remains and that of
      immature individuals. In the present work, we have established a sensitive and
      reliable method, based on amplification of the single-copy amelogenin-encoding
      gene (AMG). The Y allele carries a small deletion in the first intron,
      facilitating the design of distinct X- and Y-specific polymerase chain reactions.
      Amplification with three primers, two of which are allele-specific, allows
      unambiguous identification of both X and Y chromosome signals in a single
      reaction, providing an internal control. For added confidence, the reaction may
      be performed in separate tubes for each allele. Using this method, the sex was
      determined from the skeletal remains of 18 individuals, including young children,
      out of 22 examined from periods ranging from 200 to around 8000 years ago. The
      state of skeletal preservation ranged from poor to good. Cortical and cranial
      bones, as well as teeth, were found to provide sufficiently preserved DNA. The
      success of retrieval of amplifiable DNA was not related either to the period or
      to the burial site. On the other hand, the method of DNA purification was
      critical. In our hands, direct DNA purification by Chelex from minute samples of
      bone/tooth powder gave the best results. This study demonstrates the
      applicability of the method for gender determination in skeletal remains from
      different periods.

PMID- 8566802
TI  - High-level production of human parathyroid hormone in Bombyx mori larvae and BmN
      cells using recombinant baculovirus.
AB  - A full-length cDNA encoding human parathyroid hormone (hPTH) containing the
      prepro region was cloned into Bombyx mori baculovirus under the control of the
      polyhedrin promoter and polyadenylation sequences. After transfection and
      generation of the recombinant baculovirus, hPTH production was examined in
      silkworm larvae and BmN cell cultures. The larvae synthesized and efficiently
      secreted the correctly processed and authentic hPTH (9.4 kDa) with no sign of
      internal degradation. In BmN cells, the major secreted form was the correctly
      sized protein, but small amounts of degraded hPTH could also be detected in the
      medium by immunoblotting. Unlike the situation in larvae, prepro-hPTH could also
      be demonstrated intracellularly in BmN cells. The concentration of hPTH in the
      larval hemolymph was about 70 mg/l, as compared to approx. 55 micrograms/l in the
      medium per 7.5 x 10(6) cells. Recombinant hPTH (re-hPTH) from the hemolymph was
      purified by reverse-phase HPLC and subjected to chemical and biological analyses.
      The authenticity of the purified re-hPTH was confirmed by N-terminal sequencing,
      amino acid composition and a mass of 9425 Da, close to the theoretical value. The
      hormone showed high-affinity receptor binding and full biological potency in
      increasing cellular cAMP.

PMID- 8566803
TI  - Plasmids with a kanamycin-resistance gene for site-directed mutagenesis using the
      oligodeoxyribonucleotide-directed dual amber method.
AB  - Plasmid vectors carrying lacZ' and kanamycin-resistance (KmR) genes were
      constructed for site-directed mutagenesis (SDM) using the
      oligodeoxyribonucleotide (oligo)-directed dual amber (ODA) method [Hashimoto
      Gotoh et al., Gene 152 (1995) 271-276]. The plasmids, designated pKF16k, pKF17k,
      pKF18k and pKF19k, correspond to the previously reported chloramphenicol
      resistant (CmR) ODA plasmids, pKF16c, pKF17c, pKF18c and pKF19c, respectively,
      but contain dual amber (am) codons in KmR instead of the CmR gene. The SDM
      procedure using the KmR ODA plasmids is essentially the same as that with CmR ODA
      plasmids, which utilizes two oligo primers for in vitro DNA synthesis, one
      (selection primer) for dual am reversions and the other (mutagenic primer) for
      the target site. The KmR ODA plasmids yield 5-10-times more DNA per culture
      volume as compared to the CmR ODA plasmids, and one can prepare selection agar
      medium simply by spreading Km solution on dried agar plate at a final
      concentration of 50-100 micrograms/ml; due to the broad range of selecting
      antibiotic resistance.

PMID- 8566804
TI  - Antibiotic-resistance cassettes for Bacillus subtilis.
AB  - The genes encoding resistance to four different antibiotics (erythromycin,
      kanamycin, tetracycline and spectinomycin) were cloned in the polylinker of
      various Escherichia coli plasmid vectors. These cassettes can be inserted into
      cloned Bacillus subtilis (Bs) genes and used to create tagged chromosomal
      disruptions after recombination into Bs and selection in the presence of the
      appropriate antibiotic.

PMID- 8566805
TI  - Nucleotide sequence of the Aspergillus niger srpA gene.
AB  - The Aspergillus niger (An) gene srpA, encoding a protein with homology to the
      signal recognition particle (SRP) 54-kDa protein from Saccharomyces cerevisiae
      (Sc), has been isolated and the nucleotide sequence determined. The putative An
      srpA gene is comprised of two exons of 78 and 1527 bp separated by a 49-bp
      intron, and encodes a protein of 534 amino acids that is 53% identical to Sc
      SRP54.

PMID- 8566806
TI  - Sequence of the Leptospira biflexa serovar patoc recA gene.
AB  - The nucleotide (nt) sequence of the recA gene of Leptospira biflexa serovar patoc
      strain Patoc I has been determined. The deduced amino acid (aa) sequence of the
      RecA protein is 387 aa long with a predicted molecular mass of 42,355 Da. The aa
      sequence has a high degree of identity to the aa sequences of many bacterial
      RecA, including Pseudomonas fluorescens, Escherichia coli and Bacillus subtilis.
      This is the first recA sequence reported for a bacterium in the order
      Spirochaetales.

PMID- 8566807
TI  - Structure and gene expression of avian cyclin D2.
AB  - Avian cyclin D2 (Cyl D2)-encoding cDNA clones were isolated from a chicken UG9 T
      cell lambda gt10 library. Sequence analysis revealed a high degree of sequence
      conservation with both the mouse and human Cyl D2, and somewhat lower similarity
      with the mouse and human Cyl D1 and D3. The homology is highest between species
      in the Cyl-box domain which is well conserved among human, mouse and chicken. A
      single 6.0-kb CYL2 mRNA is produced in both avian B- and T-cells, as expected.

PMID- 8566808
TI  - Sequence of mouse CDC47, a member of the minichromosome maintenance (Mcm) family
      involved in the DNA replication licensing system.
AB  - The cDNA encoding a mouse protein, mCDC47, belonging to the minichromosome
      maintenance (Mcm) family possibly involved in the DNA replication licensing
      system, was cloned and sequenced. Its deduced amino acid (aa) sequence contained
      a putative DNA-dependent ATPase motif commonly observed in the family, and a zinc
      finger-like domain found in some members of the family.

PMID- 8566809
TI  - Monovalent phage display of human interleukin (hIL)-6: selection of superbinder
      variants from a complex molecular repertoire in the hIL-6 D-helix.
AB  - Phage display of proteins can be used to study ligand-receptor interaction and
      for the affinity-maturation of binding sites in polypeptide hormones and/or
      cytokines. We have expressed human interleukin-6 (hIL-6) on M13 phage in a
      monovalent fashion as a fusion protein with the phage coat protein, pIII. Phage
      displayed hIL-6 is correctly folded, as judged by its ability to interact with
      conformation-specific anti-hIL-6 monoclonal antibodies (mAb) and with the hIL-6
      receptor complex in vitro. We set up an experimental protocol for the efficient
      affinity selection of hIL-6 phage using the extracellular portion of the hIL-6
      receptor alpha (hIL-6R alpha) fixed on a solid phase. This system was used to
      affinity-purify from a library of hIL-6 variants, in which four residues in the
      predicted D-helix of the cytokine were fully randomized, mutants binding hIL-6R
      alpha with higher efficiency than the wild type. When the best-binder variant
      Q175I/Q183A was combined with a previously identified superbinder S176R [Savino
      et al., Proc. Natl. Acad. Sci. 90 (1993) 4067-4071], a triple-substitution mutant
      Q175I/S176R/Q183A (hIL-6IRA) was obtained with a fivefold increased hIL-6R alpha
      binding and a 2.5-fold enhanced biological activity.

PMID- 8566810
TI  - Identification of functional interaction sites on proteins using bacteriophage
      displayed random epitope libraries.
AB  - We describe a phage-display-based method to identify epitopes or interaction
      sites on proteins. DNA encoding the protein of interest is partially degraded
      with DNase I to generate random fragments of 50-200 bp. These fragments are then
      cloned into a phagemid vector that has been modified to allow the expression of
      the random fragments and the construction of a (bacterio)phage-displayed random
      epitope library. Phages displaying functional epitopes can be selected from these
      libraries by affinity selection or panning. To test this method we have
      constructed a random-epitope library for human plasminogen-activator inhibitor 1
      and used this library to map the epitope of a monoclonal antibody (mAb) directed
      against this protein. By alignment of the selected overlapping epitope-containing
      fragments, we were able to locate the epitope of the mAb on a stretch of 39 amino
      acids spanning from E128 to V166. The approach may also be applied to more
      complex systems than single-protein genes, such as viral genomes or complete cDNA
      libraries.

PMID- 8566811
TI  - An improved TnMax mini-transposon system suitable for sequencing, shuttle
      mutagenesis and gene fusions.
AB  - A new collection of mini-transposons (mini-Tn) of the previously described TnMax
      series [Haas et al, Gene 130 (1993a) 23-31] has been constructed. The transposons
      (Tn) bear genes conferring resistance to either chloramphenicol (Cm) or kanamycin
      (Km). Each member of the new series (TnMax5-TnMax11) contains the general M13
      forward (M13-FP) and reverse (M13-RP1) sequencing primers close to the inverted
      repeats (IR), facilitating the rapid and convenient determination of the DNA
      sequences flanking the transposon insertion site. Furthermore, the mini-Tn
      possess the infrequently occurring NotI sites, allowing the localization of genes
      on macro-restriction maps of bacterial species. Some derivatives contain
      promoterless trp-lacZ (TnMax11), xylE (TnMax10), phoA (TnMax6) or blaM (TnMax7,
      TnMax9) genes next to the IR, suitable for the generation of in vivo gene- and
      operon fusions to study gene regulation, protein export, or to determine the
      topology of proteins in bacterial membranes. A set of conjugative minimal plasmid
      vectors (pMin1, pMin2) are used to select for TnMax insertions into the cloned
      insert, rather than the vector sequences. Due to the small size of the mini-Tn,
      and a simple and efficient mutagenesis procedure, the TnMax system is a useful
      tool for targeting and sequencing of cloned genes in Escherichia coli, and
      especially for shuttle mutagenesis of bacterial species which cannot be targeted
      by direct transposition.

PMID- 8566812
TI  - A new restriction-modification system, KpnBI, recognized in Klebsiella
      pneumoniae.
AB  - A unique DNA restriction-modification (R-M) system has been identified in the
      GM236 strain of Klebsiella pneumoniae using the newly isolated phage, SBS. The
      system was designated KpnBI. The gene (hsdRKpnBI) complementing the restriction
      activity of the KpnBI system was cloned in pBR322. The nucleotide sequence of the
      cloned DNA revealed one open reading frame (ORF) of 3035 bp. Analysis of the
      deduced amino-acid sequence shows seven helicase motifs which are common to the
      restriction (R) subunit of both type-I and type-III R-M systems. Computer
      analysis (Dendrogram) of the R polypeptide of KpnBI suggests a closer
      relationship to EcoR124/3I, a member of type-IC family, than to other
      representative type-I and type-III systems.

PMID- 8566813
TI  - Rapid purification of recombinant proteins fused to chicken avidin.
AB  - A novel expression vector (pAVEX16C) has been constructed that directs the
      synthesis of desired polypeptides as fusions with the C terminus of chicken egg
      white avidin (Avd). With this and a commercial GST gene (encoding glutathione S
      transferase) fusion vector (pGEX-3X, Pharmacia), we produced Avd as fusions C-
      and N-terminally linked to GST in Escherichia coli. By using the Avd tail and a
      simple affinity purification protocol, including biotin-agarose, we were able to
      obtain 1-2 micrograms/ml of highly purified Avd::GST and GST::Avd from crude
      bacterial lysates. The produced proteins were, to a great extent, in soluble
      fraction when the cells were grown at 22 degrees C and disrupted with a
      detergent, N-laurylsarcosine. The fusion proteins could also be affinity-purified
      with the GST tail using glutathione-Sepharose 4B, but the yield of GST::Avd was
      significantly lower than when using the Avd tail. Our results therefore indicate
      that it is possible to produce, in E. coli, biologically active fusion proteins
      consisting of Avd C- or N-terminally linked with the desired protein which then
      can easily be purified by a simple affinity chromatography procedure.

PMID- 8566814
TI  - The creation of a camptothecin-sensitive Escherichia coli based on the expression
      of the human topoisomerase I.
AB  - The synthesis of the human topoisomerase I (Topo I) in Escherichia coli (Ec)
      results in phenotypes consistent with the appearance of a DNA-relaxing activity.
      High-level expression was problematic and recloning the gene in a reduced-copy
      number plasmid under more stringently regulated control produced a stable
      plasmid. An Ec strain with an inducible sensitivity to the eukaryotic Topo I
      poison, camptothecin (CPT), was constructed by introducing a mutation (imp4312)
      known to enhance the permeability of Ec to a wide variety of compounds. We are
      able to infer that CPT sensitivity in Ec involves DNA damage by noting elevated
      sensitivity in a repair-deficient recA strain and by observing the induction of a
      sulA::lac fusion following exposure to the drug.

PMID- 8566815
TI  - Two different operons for the same function: comparison of the Salmonella
      typhimurium nrdAB and nrdEF genes.
AB  - By using a P22 phage-mediated cloning system, the nrdAB genes of Salmonella
      typhimurium (St), encoding a ribonucleotide reductase (RR) of class I, have been
      isolated. The coding regions of the St nrdAB operon show a very high identity
      with those of the homologous operon of Escherichia coli (Ec). Nevertheless, there
      are significant differences in their promoter regions since, although the
      promoters of both operons present two DnaA boxes, these boxes are located
      downstream from the transcription start point in St, being upstream in Ec.
      Moreover, the deduced amino-acid sequences of the St nrdAB showed a very limited
      overall identity (28%) with the products of St nrdEF, which encode a second class
      I RR. Expression of St nrdAB and nrdEF is inducible by hydroxyurea, an inhibitor
      of RR activity. Alignment of the promoter regions of the nrdAB and nrdEF operons
      of both St and Ec reveals the presence of a consensus sequence. St is the first
      organism from which two different RR belonging to the same biochemical class are
      known.

PMID- 8566816
TI  - Cloning and characterization of the gene (rfc) encoding O-antigen polymerase of
      Pseudomonas aeruginosa PAO1.
AB  - The lipopolysaccharide (LPS) O-antigen polymerase is the product of the rfc gene.
      Loss of O-antigen polymerase activity due to mutation in rfc gives rise to a
      characteristic LPS phenotype known as core-plus-one or semi-rough, wherein the
      LPS core is capped with a single oligosaccharide unit. Pseudomonas aeruginosa
      (Pa) AK1401, a derivative of strain PAO1 (serogroup O5), expresses a semi-rough
      LPS; this mutant phenotype was complemented by a 2.2-kb NsiI-SacI fragment of Pa
      PAO1 DNA. Sequence analysis of this fragment revealed a 1317-bp open reading
      frame (ORF) potentially encoding a 438-amino-acid (aa) protein of 48,849 Da. This
      DNA sequence and the inferred aa sequence contain many of the features of other O
      antigen polymerases, including an aberrantly low G + C content (particularly
      apparent in the high-G + C background of Pa), an unusual codon usage pattern, and
      a hydrophobicity profile indicative of a membrane protein. A 345-bp fragment
      internal to the ORF hybridized to genomic DNA from two of ten Pa serogroup
      strains examined by Southern blot; these two strains express O antigens
      structurally related to that of strain PAO1.

PMID- 8566818
TI  - The argG gene of Streptomyces clavuligerus has low homology to unstable argG from
      other actinomycetes: effect of amplification on clavulanic acid biosynthesis.
AB  - The argG gene of Streptomyces clavuligerus (Scl) has been cloned by
      complementation of argG mutants of Escherichia coli and S. lividans (Sl). The
      argG nucleotide (nt) sequence showed that it corresponds to a new type of argG
      different from the corresponding genes of S. coelicolor (Sco) and Sl. It encodes
      a 43,250-Da protein that showed higher similarity to argininosuccinate
      synthetases (ASS) from Methanococcus vannielii and Methanosarcina barkeri than to
      ASS deduced from other Streptomyces argG. No hybridization of the Scl argG was
      found with the homologous genes of Sl or Sco. The argH gene was located
      downstream from argG in Scl. The genomic region around argG and argH in Scl was
      different from the homologous regions in other Streptomyces and is not
      genetically unstable, unlike in Sco and Sl. Amplification of argG in transformant
      Scl[pULAR113] results in a 2.3-fold increase in the production of clavulanic acid
      (CA) in relation to the control strain Scl[pIJ699].

PMID- 8566817
TI  - Sequencing and characterization of the downstream region of the genes encoding
      nitrite reductase and cytochrome c-551 (nirSM) from Pseudomonas aeruginosa:
      identification of the gene necessary for biosynthesis of heme d1.
AB  - The nirC and nirF genes were identified downstream from nirSM, the structural
      genes encoding nitrite reductase (NIR) and cytochrome c-551 from Pseudomonas
      aeruginosa (Pa). The nirC gene encodes a probable c-type cytochrome with a signal
      sequence for membrane translocation. The nirF gene codes for a protein of 392
      amino acids. A nirF mutant of Pa, constructed by marker exchange mutagenesis,
      synthesized an inactive NIR protein whose activity was restored by adding
      purified heme d1. The mutant strain produced an active NIR, when it was
      transformed by a broad-host-range plasmid carrying nirF. These results showed
      that the product of nirF was essential for the biosynthesis of heme d1 in Pa.

PMID- 8566819
TI  - Analysis of the rpoD gene encoding the principal sigma factor of Pseudomonas
      putida.
AB  - The gene (rpoD) encoding the principal sigma factor of Pseudomonas putida (Pp)
      was cloned and sequenced. The amino-acid sequence deduced from the nucleotide
      sequence of rpoD contained sequences with significant similarity to the conserved
      region of the principal sigma factors. In vivo transcriptional analyses revealed
      that the Pp rpoD is transcribed as a monocistronic mRNA of 2.1 kb and that the
      transcription of rpoD is under control of the heat-shock (HS) response. The
      transcription start point (tsp) of the gene was determined and found to be
      different depending on either normal growth (at 30 degrees C) or HS (at 42
      degrees C) conditions. The possible promoter sequences for the principal (sigma
      70) and the HS RNA polymerase of Pseudomonas were located in the upstream region
      of the tsp.

PMID- 8566820
TI  - Identification of five Rhodobacter capsulatus genes encoding the equivalent of ND
      subunits of the mitochondrial NADH-ubiquinone oxidoreductase.
AB  - We previously reported the sequencing of two genes (ndhA and ndhI) encoding two
      of the subunits of the type-I NADH-ubiquinone oxidoreductase from Rhodobacter
      capsulatus (Rc). The present paper deals with the cloning and characterization of
      a chromosomal fragment clustering five new Rc genes which encode subunits of this
      enzyme. This gene cluster is located immediately downstream from ndhA and ndhI,
      and also contains two unidentified open reading frames (urf2, urf3). The five
      genes, nuoJ, nuoK, nuoL, nuoM and nuoN, encode proteins related, respectively, to
      mitochondrial (mt) subunits ND6, ND4L, ND5, ND4 and ND2. The overall organization
      of the nuo genes identified in Rc shows similarity to that of the Paracoccus
      denitrificans (Pd) nqo gene cluster.

PMID- 8566821
TI  - Ocular findings in Japanese women with nevus of Ota.
AB  - BACKGROUND: Nevus of Ota is common in Japanese women, but most patients are not
      examined ophthalmologically. METHODS: We performed ophthalmologic examinations on
      16 Japanese women who had had bluish pigmentation in the periorbital region,
      sclera, and conjunctiva since birth. RESULTS: Fifteen patients had unilateral
      involvement, and one had bilateral lesions. The visual acuities were good, and
      the intraocular pressures were within normal range. All patients had a negative
      family history. Three patients had light pigmentation in the optic disc in the
      affected eye. CONCLUSION: We believe that optic disc pigmentation associated with
      nevus of Ota, as found in these three patients, may be common but have been
      rarely described.

PMID- 8566822
TI  - Immunohistochemical localization of epidermal growth factor receptor and
      epithelial antigen in tumors of the human conjunctiva, eyelid, lacrimal gland,
      and orbit.
AB  - BACKGROUND: Increased numbers of epidermal growth factor (EGF) receptors are
      observed in squamous cell carcinomas of human lung, head, neck, and cervix. We
      studied the presence of EGF receptors and epithelial antigen in some ophthalmic
      lesions. METHODS: Immunohistochemical staining for EGF receptors was assessed in
      tumors of human conjunctiva, eyelid, lacrimal glands, and orbit with monoclonal
      antibodies (EGF-R1 and clone 29.1). Reactivity of Ber-EP4, which recognizes
      epithelial antigen, was also examined. RESULTS: Strong staining of EGF-R1 and
      clone 29.1 and weak to moderate staining of Ber-EP4 were demonstrated in
      conjunctival squamous cell carcinomas. Cell membranes of conjunctival papilloma
      were moderately or strongly stained with these antibodies. Ductal components in
      sebaceous gland adenoma of the eyelid and pleomorphic adenoma of the lacrimal
      gland were positively stained. The antibodies did not bind to reactive lymphoid
      hyperplasia of the orbit and Wegener's granulomatosis. Relatively good
      correlation for immunostaining reaction was observed among EGF-R1, clone 29.1,
      and Ber-EP4 in each tumor. CONCLUSION: Immunostaining using EGF-R1, clone 29.1,
      and Ber-EP4 may be useful in differentiating epithelial tumors from non
      epithelial lesions. Strong immunostaining for EGF receptor may be the hallmark of
      epidermoid malignancy.

PMID- 8566823
TI  - Indocyanine green angiography of choroidal tumors.
AB  - BACKGROUND: Fluorescein angiography (FA) has been widely used in the diagnostic
      evaluation of choroidal tumors. Indocyanine green angiography (ICG-A), which
      permits better visualization of choroidal vasculature than FA, has been recently
      introduced into clinical practice. Only few reports exist on the ICG-A
      characteristics of choroidal tumors. METHODS: The fluorescein and indocyanine
      green angiograms of 61 patients were assessed. These included 14 patients with
      choroidal nevi, 30 with malignant melanomas, 7 with suspected melanomas or
      atypical nevi, 5 with hemangiomas and 5 with metastases. RESULTS: The outline of
      pigmented tumors was more accurate on ICG-A than on FA. Characteristic patterns
      were seen in all intra-ocular tumors with ICG-A, so it was possible to
      distinguish hemangiomas from malignant lesions. Characteristic features of
      malignant melanomas include abnormal vascular pattern and marginal late dye
      leakage. None of the benign lesions showed these features. In suspected
      melanomas, the presence of abnormal choroidal vascular patterns and/or late dye
      leakage on ICG-A may indicate malignancy. CONCLUSION: The study suggests that ICG
      A can yield additional information that is useful in differentiating amongst
      choroidal tumors. Better delineation of pigmented lesions with ICG-A allows more
      accurate treatment planning and follow-up.

PMID- 8566824
TI  - Determination of the neuroretinal rim area using the horizontal and vertical disc
      and cup diameters.
AB  - BACKGROUND: This study evaluated whether the neuroretinal rim area can be
      calculated on the basis of the horizontal and vertical diameters of the optic
      disc and cup applying the formula of an ellipse. METHODS: Color stereo optic disc
      photographs of 587 normal subjects and 1193 patients with glaucoma were
      morphometrically examined. In a first method, the areas of the optic disc and cup
      were planimetrically measured and the area of the neuroretinal rim was determined
      as optic disc area minus cup area. In a second method, the optic disc and cup
      were assumed to have an elliptical shape. Their areas were calculated by applying
      the formula of an ellipse, taking into account their horizontal and vertical
      diameters. As in the first method, the rim area was then determined as disc area
      minus cup area. RESULTS: The values of the neuroretinal rim area as measured
      using the first method differed by 0.05 +/- 0.05 mm2 from the values as
      calculated by the second method. The average error was 2.8 +/- 2.9% for the
      normal group and 8.2 +/- 20.8% for the glaucoma patients. It increased with
      decreasing neuroretinal rim area and increasing mean visual field defect.
      CONCLUSIONS: For clinical purposes, the neuroretinal rim area can be determined
      on the basis of the horizontal and vertical diameters of the optic disc and cup.
      The horizontal and vertical disc and cup diameters being determinable upon
      ophthalmoscopy, this finding is important for the direct measurement of optic
      disc morphology during any ophthalmoscopic examination.

PMID- 8566825
TI  - Oxidative reactions in the tear fluid of patients suffering from dry eyes.
AB  - PURPOSE: To evaluate whether products of oxidative and inflammatory reactions are
      detectable in the tear fluid of patients suffering from dry eyes. METHODS: The
      tear fluid of 217 patients (397 eyes) was sampled. Criteria for grouping of the
      patients were (1) basic secretion test ("sicca 1": BST = 0-5 mm, n = 78 eyes;
      "sicca 2": BST = 6-10 mm, n = 109 eyes) and (2) subjective symptoms (normal BST,
      burning, foreign body sensations, tearing, dryness of the eyes: n = 78 eyes). One
      group of healthy patients (normal BST, n = 132 eyes) served as controls. Lipid
      peroxide levels and myeloperoxidase activity, as parameters for oxidative tissue
      damage and inflammatory activity, were determined in the tear fluid. Those
      patients whose consent could be obtained were subjected to the rose bengal test
      (sicca 1: 56 eyes; sicca 2: 97 eyes; subjective symptoms: 44 eyes; controls: 49
      eyes). The correlation between BST and rose bengal test results was calculated.
      RESULTS: Lipid peroxides were significantly (P < 0.05) higher in the groups sicca
      1 and subjective symptoms than in healthy controls, as was the inflammatory
      activity in groups sicca 1, sicca 2 and subjective symptoms. Additionally, the
      inflammatory activity in the group sicca 1 was significantly (P < 0.05) higher
      than in the groups sicca 2 and subjective symptoms. No evidence of a significant
      correlation between BST and rose bengal test results was observed. CONCLUSIONS:
      Both oxidative tissue damage and polymorphonuclear leukocytes indicating an
      oxidative potential occur in the tear film of patients suffering from dry eyes.
      These reactions lead to severe damage of the involved tissue. Free radicals and
      inflammation may be involved in the pathogenesis or in the self-propagation of
      the disease.

PMID- 8566826
TI  - Retinal and choroidal responses to panretinal photocoagulation: an
      ultrastructural perspective.
AB  - BACKGROUND: There have been few histological or ultrastructural studies of the
      outer retina and choriocapillaris following panretinal photocoagulation therapy.
      This investigation examines the long-term morphological effects of panretinal
      photocoagulation in two patients with type II diabetes who had received laser
      treatment more than 6 months prior to death. METHODS: Regions of retina and
      choroid from each patient were fixed in 2.5% glutaraldehyde, dissected out and
      examined using light microscopy and scanning and transmission electron
      microscopy. RESULTS: After removing the neural retina, scanning electron
      microscopy of non-photocoagulated areas of the eye cups revealed normal
      cobblestone-like retinal pigment epithelial (RPE) cells. Regions with laser scars
      showed little RPE infiltration into the scar area, although large rounded cells
      often appeared in isolation within these areas. Sections of the retina and
      choroid in burn regions showed a complete absence of the outer nuclear layer and
      photoreceptor cells, with the inner retinal layers lying in close apposition to
      Bruch's membrane. Non-photocoagulated regions of the retina and choroid appeared
      normal in terms of both cell number and cell distribution. The RPE layer was
      absent within burn scars but many RPE-like cells appeared markedly hypertrophic
      at the edges of these regions. Bruch's membrane always remained intact, although
      the underlying choriocapillaris was clearly disrupted at the point of
      photocoagulation burns, appearing largely fibrosed and non-perfused. Occasional
      choroidal capillaries occurring in this region were typically small in profile
      and had plump non-fenestrated endothelium. CONCLUSIONS: This study outlines
      retinal and choroidal cell responses to panretinal photocoagulation in diabetic
      patients and demonstrates an apparent reduction in the capacity of these tissues
      to repair laser damage.

PMID- 8566827
TI  - The role of inner wall retinectomy in the management of juvenile retinoschisis.
AB  - PURPOSE: The purpose of this paper is to describe the technique and application
      of relief of vitreous traction and inner wall retinectomy in the management of
      juvenile retinoschisis (JRS). In addition, during the course of this study a
      previously undescribed form of tractional retinal detachment associated with
      retinal schisis was observed. METHODS: Six eyes of four children with visual
      field and/or central vision loss underwent vitrectomy (in five of the six eyes
      the lenses were preserved), inner wall retinectomy and photocoagulation for
      rhegmatogenous/schisis retinal detachment, tractional retinal detachment and
      reduced central vision secondary to intraschisis hemorrhage overhanging the
      macula. RESULTS: The children were followed up for 1 to 4 years. All eyes showed
      anatomic reattachment. Three of the four eyes that could be tested for vision
      showed improved visual function postoperatively. One eye showed marked
      enlargement of visual field and central visual acuity improvement from 20/200
      preoperatively to 20/50 postoperatively. CONCLUSION: Inner wall retinectomy can
      be a useful ajunct in the management of the retinal complication of JRS.
      Appropriate case selection of eyes with associated central traction retinal
      detachment can result in improved visual field and central visual acuity. The
      success of this technique suggests that the mechanical and/or pharmacological
      relief of vitreous traction may be able to alter the clinical course of JRS.

PMID- 8566828
TI  - Ocular findings in cystic fibrosis patients receiving vitamin A supplementation.
AB  - BACKGROUND: Vitamin A deficiency with eye symptoms has been reported in patients
      with cystic fibrosis who received the recommended daily intake of vitamin A.
      METHODS: We measured serum retinol, dark adaptation, contrast sensitivity, and
      dry eye status in 35 adult cystic fibrosis patients to ascertain whether they had
      ocular signs or symptoms. RESULTS: Median serum retinol concentration was 1.95
      mumol/l, range 1.08-4.01 mumol/l, with no values indicating vitamin A deficiency.
      Retinal light sensitivity was normal. Nineteen patients had reduced contrast
      sensitivity. Conjunctival imprints all showed plenty of goblet cells, but were
      characteristic of dry eye in 42% of patients (n = 14). Decreased tear film
      stability was found in 49% (n = 17), tear production was low in 31% (n = 11), and
      23% (n = 8) showed an increased amount of dying epithelial cells. Nine patients
      (26%) had keratoconjunctivitis sicca according to the Copenhagen criteria.
      CONCLUSION: Our patients had no biochemical or clinical signs of vitamin A
      deficiency. We speculate that the high incidence of dry eye could be a primary
      manifestation of cystic fibrosis.

PMID- 8566829
TI  - Detection of herpes simplex virus after penetrating keratoplasty by polymerase
      chain reaction: correlation of clinical and laboratory findings.
AB  - BACKGROUND: The study was carried out to investigate the possible correlation of
      clinical findings, histopathologic features and detection of herpes simplex virus
      DNA in corneal buttons obtained after penetrating keratoplasty. METHODS: We
      examined 47 consecutive corneal buttons sent for histopathologic examination by
      light microscopy and using the polymerase chain reaction for the detection of
      HSV1 and HSV2. Twenty-one corneal buttons from eyes with bullous keratopathy
      served as controls. RESULTS: The 47 cases were graded from the clinical
      information available as unproven, suspected and clinically proven cases of
      herpetic keratitis. This grading did not correlate to specific histopathologic
      features or to the results of HSV1 DNA testing. None of the cases were positive
      for HSV2 DNA. CONCLUSION: HSV DNA was detected in some of the cases of clinically
      unsuspected herpetic keratitis. This technique of demonstrating the presence or
      absence of HSV in the cornea after keratoplasty is more reliable than clinical
      data or histopathologic findings and may be important in cases of recurrent
      inflammatory episodes involving grafts after keratoplasty.

PMID- 8566830
TI  - A local challenger of ocular calciphylaxis in patients with chronic renal
      failure: a hypothesis.
AB  - BACKGROUND: It is generally accepted that the elevated calcium phosphate product
      in dialysis patients is associated with the development of extraskeletal
      calcification. There is, however, no clear association between the raised levels
      of calcium and phosphate ions and the degree of limboconjunctival calcification.
      This article focuses on the role of tissue devitalisation in the development of
      ocular calcification. METHODS: Local injury of the outer eye can be visualised by
      the Lissamine green staining test. We measured the pre- and postdialysis staining
      score in 38 dialysis patients. The differences between pre- and postdialysis tear
      fluid secretion and tearfilm stability were also assessed, as was the degree of
      limboconjunctival calcification. Serum calcium and phosphate levels were measured
      in all patients. RESULTS: In 14 of the 38 patients, demonstrable tissue injury
      was present as a result of a recurrent decrease of tear secretion after each
      dialysis session. There was a statistically significant association between the
      degree of limboconjunctival calcification and both the difference between the pre
      and postdialysis Lissamine green staining score and the total number of
      haemodialysis sessions. CONCLUSION: Local factors, such as minor tissue injury of
      the limboconjunctival epithelium, referred to as "local challenger", are more
      likely to determine the degree of ocular calcification in dialysis patients than
      are systemic factors. Tissue injury of the outer eye in these patients is the
      result of a chronic decrease of tear fluid that occurs after each hemodialysis
      session.

PMID- 8566831
TI  - Blood-retina barrier in acute retinal branch vein occlusion.
AB  - BACKGROUND: Extensive clinical studies on retinal branch vein occlusion have not
      yet been able to clarify its pathogenesis. A study designed to look at the
      associated blood-retina barrier changes may contribute to a better understanding
      of the different forms of evolution of this pathology. METHODS: A prospective
      study was done in seven patients with recent large temporal branch vein
      occlusion. Vitreous fluorophotometry, fluorescein angiography and retinal colour
      photography were performed within the 1st week after the onset of symptoms, 1
      week later, and at 12 and 24 weeks. RESULTS: A more marked blood-retina barrier
      breakdown was found at 1, 2, 12 and 24 weeks in the eyes that later developed
      extensive capillary nonperfusion. CONCLUSIONS: Our results suggest that the
      breakdown of the blood-retina barrier may play an important role in the
      subsequent development of retinal nonperfusion in eyes with large branch vein
      occlusion. We postulate that the eyes that will present later extensive capillary
      nonperfusion develop, from the initial stages of the disease, a progressive
      "ischaemic capillaropathy" characterized by blood-retina barrier breakdown.
      Retinal pigment epithelium degeneration and arterial lumen narrowing, secondary
      to the vein obstruction, may help to increase and perpetuate the blood-retina
      barrier breakdown during the first 6 months after the occlusion.

PMID- 8566832
TI  - Corneal endothelial wound repair in normal and mitotically inhibited cultures.
AB  - BACKGROUND: The aim of the present study was to compare the morphology,
      proliferative activity and cytoskeletal organization of bovine corneal
      endothelial cells during wound healing under normal and mitotically inhibited
      conditions. METHODS: Cell cultures were grown to confluency and incubated with
      the mitotic inhibitor 5-fluorouracil (5-FU; 2.5 micrograms/ml) followed by a
      touch wound. Control cultures were maintained without 5-FU. Mitotic activity, F
      actin, vinculin, vimentin and connexin 43 localization were evaluated before,
      during and after wound closure. RESULTS: 5-FU inhibited irreversibly the mitotic
      activity of corneal endothelial cells during the whole wound healing process. In
      the presence of 5-FU, a high degree of polymegathism and delay in actin and
      vinculin redistribution to the cell borders after wound closure was observed.
      Vimentin and connexin 43 immunolabeling revealed only slight differences between
      5-FU-treated and control cultures. CONCLUSIONS: Significant changes in cell
      geometry and cytoskeletal organization in the amitotic corneal endothelium became
      manifested only after wounding. These changes may influence cell-cell and cell
      matrix interactions as well as functional restoration of the monolayer after
      wound closure.

PMID- 8566833
TI  - Modeling the effects of anterior chamber fluid viscosities on intraocular
      pressure following glaucoma filtering surgery.
AB  - BACKGROUND: Hypotonia, flat anterior chamber, and choroidal effusion are not
      infrequent and undesirable consequences of glaucoma filtering surgery. Methods
      developed so far to prevent or combat these complications have only been
      moderately successful. Viscous fluids admixed to the aqueous humor are known to
      influence fluid dynamics and hence intraocular pressure during variable time
      intervals following surgery. It was the intention of the authors to develop a
      mathematical model which predicts the influence of sodium hyaluronate determining
      the intraocular pressure following injection into the anterior chamber. METHODS:
      The model is based on first-order approximations and derives from the theory of
      rheology and fluid dynamics in narrow tubes, and is essentially based on Hagen
      Poiseuille's law. RESULTS: The predictions of the model (to be published in a
      paper to follow) were verified in experiments on owl monkeys and showed a high
      degree of predictive power. CONCLUSIONS: One may conclude that sodium
      hyaluronate, injected once or repeatedly with fine canulas into the anterior
      chamber, qualifies as an important tool to maintain normal on near-normal
      intraocular pressure in the immediate and late postoperative phase following
      surgery.

PMID- 8566835
TI  - Effect of c-kit ligand, stem cell factor, on mediator release by human intestinal
      mast cells isolated from patients with inflammatory bowel disease and controls.
AB  - The regulation of mediator release in human intestinal mast cells is largely
      unknown. Apart from IgE receptor crosslinking no secretagogues have been
      described so far. This study examined the effect of two cytokines (c-kit ligand
      and interleukin 3) and other agonists on human intestinal mast cell function.
      Cells were isolated from surgery specimens of 47 patients undergoing intestinal
      resection because of tumours or inflammatory bowel disease. Cell suspensions
      contained 3.6% mast cells (mean of 50 experiments). After preincubation without
      or with c-kit ligand or interleukin 3, cells were stimulated by IgE receptor
      crosslinking, C5a or formyl-methionyl-leucyl-phenylalanine (fMLP). Histamine and
      sulphidoleukotriene release was measured in supernatants. The sequential
      stimulation of the cells with c-kit ligand and IgE receptor crosslinking induced
      the release of high amounts of histamine and leukotrienes, whereas each agonist
      by itself induced only marginal mediator release. Interleukin 3 induced no
      release by itself, but enhanced the IgE receptor dependent release, possibly by
      an indirect mechanism. No significant mediator release was seen in response to
      C5a and fMLP, even if the cells were pretreated with c-kit ligand. The mediator
      release, particularly that of leukotrienes, was higher in cells isolated from
      actively inflamed tissue from patients with inflammatory bowel disease compared
      with controls. In conclusion, it was found that, apart from IgE receptor
      crosslinking, c-kit ligand and interleukin 3 regulate mediator release in human
      intestinal mast cells. The enhancement of mediator release by cytokines may be of
      particular relevance in the pathogenesis of inflammatory bowel diseases and food
      intolerance reactions.

PMID- 8566834
TI  - Labelled leucocyte scintigraphy in inflammatory bowel disease: clinical
      applications.

PMID- 8566836
TI  - Comparison of effects of calcium carbasalate and aspirin on gastroduodenal
      mucosal damage in human volunteers.
AB  - Calcium carbasalate is a therapeutically active salicylate which seems to cause
      less gastroduodenal mucosal damage than aspirin in laboratory animals. This
      endoscopist-blinded, randomised, cross over trial aimed to compare acute gastric
      mucosal damage in 20 healthy volunteers treated with acetyl salicylic acid (ASA)
      (650 mg three times daily) and effervescent calcium carbasalate (ECC) (826.8 mg
      three times daily) bioequivalent to 650 mg ASA over a five day period. Endoscopy
      was performed immediately before treatment and on day 5 of each treatment. Serum
      salicylate, thromboxane B2, and gastric mucosal prostaglandin E2 (PGE2)
      concentrations were measured after endoscopy. ECC caused fewer gastric mucosal
      erosions than ASA. The total number of gastric erosions was 23.8 (16.1) in the
      ASA treated subjects compared with 9.1 (8.7) in ECC treated subjects (p = 0.004).
      Differences between ASA and ECC were significant for both the gastric antrum and
      body, and for both haemorrhagic and non-haemorrhagic erosions. The mean gastric
      body Lanza score for mucosal damage was lower after ECC than ASA (p = 0.003). The
      visual analogue score for gastric body damage was lower for ECC (16.9 mm (15.9))
      than for ASA (32.7 mm (20.8)), p = 0.008. Serum salicylate concentrations were
      similar after both preparations (ASA: 66 (23) mg/l, versus ECC: 58 (17) mg/l,
      NS). Serum thromboxane B2 was similarly reduced using both preparations-97.2
      (3.5)% inhibition with ASA, 95.2 (5.5)% inhibition with calcium carbasalate (NS).
      Suppression of gastric mucosal PGE2 synthesis was similar with both preparations
      (ASA: 83.4 (17.1)%; ECC 84.3 (12.9)%; NS). It is concluded that ECC causes
      significantly less gastroduodenal mucosal damage than ASA administered at
      bioequivalent doses as judged by serum salicylate, serum thromboxane, and mucosal
      PGE2 values. ECC may therefore be a less harmful alternative treatment to plain
      ASA.

PMID- 8566837
TI  - 5-Aminosalicylic acid inhibits the impaired epithelial barrier function induced
      by gamma interferon.
AB  - Gamma interferon (IFN gamma) impairs epithelial barrier function and induces HLA
      DR expression on colonic cancer cell lines. Salicylates have been shown to reduce
      IFN gamma induced HLA-DR expression. The effect of 5-aminosalicylic acid (5-ASA)
      on IFN gamma induced changes in transepithelial resistance and permeability was
      investigated in HT29 clone 19A and Caco 2 monolayers. Monolayers were incubated
      with different concentrations of IFN gamma (100, 500, 1000, and 3000 U/ml) and 5
      ASA. IFN gamma induced class II expression in a time and dose dependent manner in
      HT29:19A but not Caco 2 cells. HT29:19A monolayers incubated with both IFN gamma
      and 5-ASA showed lower HLA-DR expression compared with monolayers incubated with
      IFN gamma alone. Electrical resistance and 14C-mannitol flux across HT29:19A
      monolayers were significantly changed by IFN gamma. Addition of both IFN gamma
      and 5-ASA to the basolateral surface of the monolayers significantly reduced
      paracellular permeability compared with addition of IFN gamma alone. These data
      show that IFN gamma is able to induce HLA-DR expression and to impair the barrier
      function of HT29:19A monolayers, and that 5-ASA reduces IFN gamma induced HLA-DR
      expression and inhibits the effects of IFN gamma on epithelial barrier function.

PMID- 8566838
TI  - Use of whole gut perfusion to investigate gastrointestinal blood loss in patients
      with iron deficiency anaemia.
AB  - Iron deficiency anaemia may be due to occult bleeding into the gut. However,
      although clinical investigations may show a high frequency of gastrointestinal
      tract disease in these patients, the cause-effect relationship between the
      lesions detected and anaemia remain uncertain. This study aimed to establish
      whether lesions detected by endoscopy or imaging of the gastrointestinal tract in
      patients with unexplained iron deficiency anaemia are bleeding continuously.
      Routine clinical tests were performed in 42 patients with unexplained iron
      deficiency anaemia referred to this unit. Whole gut lavage and assay of
      haemoglobin in the gut perfusate were also performed. The main outcome measures
      were clinical diagnoses (by imaging and endoscopy of the upper gastrointestinal
      tract and colon); the concentration of haemoglobin in whole gut lavage fluid; and
      the calculated gastrointestinal blood loss per day. There were 73 clinical,
      dietary, or iatrogenic factors of possible aetiological importance in the 42
      patients--poor diet (10), gross gastrointestinal abnormality (34 in 28 patients),
      malabsorption (14), coagulation problems (6), and NSAID use (9). The gut lavage
      test showed, however, that at the time the test was performed, only eight
      patients were losing more than 2 ml blood daily into the gut, including all four
      with colonic cancer, one with diffuse gastric vascular ectasia, and one with
      severe ulcerative oesophagitis. It is concluded that occult gastrointestinal
      bleeding sufficient to cause anaemia was evident in only 19% of 42 patients.
      There was a high frequency of other potential causes of iron deficiency in the
      remainder, suggesting that most of the gastrointestinal diseases and lesions
      detected in them were probably coincidental. Factors other than blood loss should
      be considered and treated in patients referred for anaemia assessment.

PMID- 8566839
TI  - Chemoembolisation with lipiodol and doxorubicin: applicability in British
      patients with hepatocellular carcinoma.
AB  - Chemoembolisation has been extensively used as primary treatment for unresectable
      hepatocellular carcinoma (HCC). In this unit, 185 patients with a new diagnosis
      of HCC not amenable to surgery were seen between 1988 and 1991. Intended therapy
      for these patients was chemoembolisation with doxorubicin (60 mg/m2) and
      lipiodol, repeated at six week intervals until it was technically no longer
      possible or until complete tumour response had been obtained. Chemoembolisation
      was possible in 67 of the 185 (37%). Reasons for exclusion were portal vein
      occlusion (n = 36), decompensated cirrhosis (n = 44), distant metastases (n = 5),
      diffuse tumour or unsuitable anatomy (tumour or vasculature) (n = 11), patient
      refusal (n = 11), and other (n = 11). Patients excluded from treatment survived
      for a median of 10 weeks (range 3 days-19 months). In patients treated, 18 had
      small HCC (< 4 cm) and 49 had large or multifocal HCC. Chemoembolisation was
      carried out a median of two sessions for small and three sessions for large
      tumours. Ten of 18 patients with small HCC showed a 50% or greater reduction in
      tumour size. Five of 49 patients with large or multifocal tumours showed a
      response to treatment. Median overall survival for treated patients was 36 weeks
      (range 3 days-4 years). One patient has subsequently undergone liver
      transplantation with no recurrence and minimal residual disease at
      transplantation. Two other patients are alive three years after
      chemoembolisation, one with no evidence of recurrent disease. No patient was
      thought suitable for surgery after their response to chemoembolisation.
      Chemotherapy related complications were seen in 22%. Complications were
      significantly more common in patients with larger tumours and poor liver reserve.
      Five patients died as a result of chemotherapy related complications. In
      conclusion, only one third of UK patients with unresectable HCC are treatable by
      chemoembolisation. Results with small tumours are encouraging, with a high
      response rate and the possibility of surgical intervention in previously
      inoperable disease. Large tumours, however, show a poor response and a
      significant incidence of side effects, suggesting that this treatment offers
      little benefit in advanced disease.

PMID- 8566840
TI  - Assessment of variceal pressure by continuous non-invasive endoscopic
      registration: a placebo controlled evaluation of the effect of terlipressin and
      octreotide.
AB  - Octreotide has been proposed for the treatment of variceal bleeding. The effects
      on portal pressure, however, have been variable in published studies. As bleeding
      is more directly related to pressure in the varices, this study investigated the
      effect on variceal pressure of octreotide and terlipressin, a vasoactive drug
      with a well established effect. Variceal pressure was measured during four to
      eight minutes by a continuous non-invasive endoscopic registration method. Thirty
      patients in whom a stable variceal pressure recording had been obtained during at
      least one minute, were randomised to receive either 2 mg terlipressin, 50
      micrograms octreotide or an identical volume of saline, as a single intravenous
      injection given over 60 seconds. For the final analysis three patients had to be
      excluded because of lack of a satisfactory recording. There were no significant
      clinical differences between the three groups of patients. Placebo administration
      did not induce significant changes, but a mean decrease in variceal pressure of 
      27% was noted with terlipressin, starting from two minutes onwards. Variceal
      pressure changes after injection of octreotide were variable and the mean change
      in pressure did not reach statistical significance. Seven of 10 patients showed a
      temporary increase in variceal pressure. In conclusion, terlipressin induces a
      significant and progressive decrease in variceal pressure but inconsistent
      variations of variceal pressure changes were seen after octreotide
      administration. This is probably related to its effect on central venous
      pressure. This study also shows that continuous variceal pressure recording with
      the non-invasive endoscopic registration technique detects in an accurate way the
      effect of vasoactive drugs on variceal pressure, because placebo injection did
      not produce significant changes.

PMID- 8566841
TI  - Distribution of lactoferrin and 60/65 kDa heat shock protein in normal and
      inflamed human intestine and liver.
AB  - Immunisation against the mycobacterial heat shock protein (hsp-65) has been
      proposed to lead to production of autoantibodies against human lactoferrin. Such
      antibodies occur in ulcerative colitis and in primary sclerosing cholangitis.
      This study analysed the distribution of hsp-65 and lactoferrin in biopsy
      specimens from patients with inflammatory bowel disease and primary sclerosing
      cholangitis and studied whether immunisation against mycobacterial hsp-65
      resulted in production of antilactoferrin antibodies and vice versa. Polyclonal
      rabbit antihuman lactoferrin and monoclonal mouse anti-hsp-65 (ML30) were used
      for immunohistochemistry on biopsy specimens from patients with inflammatory
      bowel disease and primary sclerosing cholangitis. Rats were immunised against
      human lactoferrin and mycobacterial hsp-65 respectively. Antibody measurements
      were done by enzyme immunosorbent assays. It was found that lactoferrin and hsp
      60/65 were not codistributed. Lactoferrin was found on vascular endothelium and
      in nonparenchymal liver cells both in inflamed and uninflamed tissues, but only
      in the hepatocytes of inflamed liver. ML30 reactivity was not inhibited by
      antilactoferrin antibodies. Rat anti-hsp-65 serum had no detectable
      antilactoferrin antibodies. In conclusion, antilactoferrin antibodies probably do
      not arise by immunisation against mycobacterial hsp-65. Both nonparenchymal cells
      and hepatocytes probably participate in clearance of lactoferrin. Endothelial
      exposure of lactoferrin may have pathogenic implications in diseases with
      antilactoferrin autoantibodies.

PMID- 8566842
TI  - Treatment of bile duct lesions after laparoscopic cholecystectomy.
AB  - From January 1990 to June 1994, 53 patients who sustained bile duct injuries
      during laparoscopic cholecystectomy were treated at the Amsterdam Academic
      Medical Centre. There were 16 men and 37 women with a mean age of 47 years.
      Follow up was established in all patients for a median of 17 months. Four types
      of ductal injury were identified. Type A (18 patients) had leakage from cystic
      ducts or peripheral hepatic radicles, type B (11 patients) had major bile duct
      leakage, type C (nine patients) had an isolated ductal stricture, and type D (15
      patients) had complete transection of the bile duct. Endoscopic retrograde
      cholangiopancreatography (ERCP) established the diagnosis in all type A, B, and C
      lesions. In type D lesions percutaneous cholangiography was required to delineate
      the proximal extent of the injury. Initial treatment (until resolution of
      symptoms and discharge from hospital) comprised endoscopy in 36 patients and
      surgery in 26 patients. Endoscopic treatment was possible and successful in 16 of
      18 of type A lesions, five of seven of type B lesions, and three of nine of type
      C lesions. Most failures resulted from inability to pass strictures or leaks at
      the initial endoscopy. During initial treatment additional surgery was required
      in seven patients. Fourteen patients underwent percutaneous or surgical drainage
      of bile collections, or both. After endoscopic treatment early complications
      occurred in three patients, with a fatal outcome in two (not related to the
      endoscopic therapy). During follow up six patients developed late complications.
      All 15 patients with complete transection and four patients with major bile duct
      leakage were initially treated surgically. During initial treatment additional
      endoscopy was required in two patients. Early complications occurred in eight
      patients. During follow up seven patients developed stenosis of the anastomosis
      or bile duct. Reconstructive surgery in the early postoperative phase was
      associated with more complications than elective reconstructive surgery. Most
      type A and B bile duct injuries after laparoscopic cholecystectomy (80%) can be
      treated endoscopically. In patients with more severe ductal injury (type C and D)
      reconstructive surgery is eventually required in 70%. Multidisciplinary approach
      to these lesions is advocated and algorithms for treatment are proposed.

PMID- 8566843
TI  - Ulcerative colitis complicated by renal cell carcinoma: a series of three
      patients.
AB  - Three patients are described in whom renal cell carcinoma was diagnosed between
      seven months and 14 years after the onset of ulcerative colitis. All three had
      required treatment with corticosteroids and azathioprine, as well as maintenance
      therapy with 5-aminosalicylate derivatives, for chronic active colitis. One
      patient had coexisting polymyalgia rheumatica; one had primary biliary cirrhosis.
      It is uncertain whether this association, which has not previously been
      described, has pathogenetic importance or has arisen simply by chance. Genetic
      predisposition or the effect of drug treatment, particularly immunosuppression,
      may be pertinent to the co-occurrence of these diseases.

PMID- 8566845
TI  - 'Fragile' liver and massive hepatic haemorrhage due to hereditary amyloidosis.
AB  - The first case of amyloidosis is reported in which spontaneous massive hepatic
      haemorrhage necessitated emergency liver transplantation. Liver transplantation,
      as a treatment for a failing liver due to amyloidosis has not been previously
      reported. At transplantation, the liver tissue was uncharacteristically friable,
      although the subsequent vascular and biliary anastomoses were uncomplicated.
      Histological examination of the liver showed a surprisingly modest amount of
      amyloid, which was shown immunohistochemically to be derived from lysozyme, and a
      striking absence of reticulin staining. Both the patient's father and paternal
      grandfather had died from spontaneous hepatic haemorrhage, and histological
      review of their liver tissue showed similarly modest deposition of lysozyme
      derived amyloid associated with loss of reticulin staining. In each case the
      quantity of amyloid was far less than would be expected to interfere with the
      mechanical integrity of the liver. This is the only report of hepatic
      disintegration associated with absence of reticulin staining, and it is probable
      that the mechanism represents a novel secondary effect of the amyloid deposits in
      the livers of this family.

PMID- 8566844
TI  - Helicobacter pylori may induce bile reflux: link between H pylori and bile
      induced injury to gastric epithelium.
AB  - Helicobacter pylori and duodenogastric reflux are both recognised as playing
      aetiological roles in chronic gastritis. This study investigated whether H pylori
      colonisation of the antral mucosa and duodenogastric reflux are independent
      phenomena or have a causal relationship. Thirty eight patients (15 men, 23 women)
      aged (mean (SD)) 48 (17) years participated. Each patient underwent gastroscopy.
      Antral biopsy specimens were taken to investigate H pylori colonisation. In
      addition BrIDA-99mTc/111In-DTPA scintigraphy was used to quantify duodenogastric
      reflux. H pylori positive patients who were found to have duodenogastric reflux
      were treated with amoxycillin (1 g/d) and metronidazole (1.5 g/d) for seven days
      and four tablets of bismuth subcitrate daily for four weeks. Follow up antral
      biopsies and scintigraphy were repeated at six months. Duodenogastric reflux
      could not be found in 18 patients, including eight (44%) who were H pylori
      positive. Ten of the 11 patients who had duodenogastric reflux (reflux % 11.6
      (9.2)), however, were H pylori positive (chi 2 = 6.26, p = 0.01). These 10
      patients were given eradication treatment. At six months, in six patients who
      became H pylori negative, duodenogastric reflux was significantly reduced from a
      pretreatment value of 14.3% to 3.3% (two tail, paired t = 2.57, p = 0.016). These
      data suggest that H pylori may induced duodenogastric reflux which may be
      important in the pathogenesis of H pylori gastritis or carcinogenesis, or both.

PMID- 8566846
TI  - Caffeine phenotyping in patients with familial adenomatous polyposis may shed
      light on sporadic colon cancer and acetylator status.

PMID- 8566847
TI  - Urinary excretion of TNF receptors.

PMID- 8566848
TI  - Gastric metaplasia and Helicobacter pylori infection.

PMID- 8566849
TI  - Transfusion for variceal bleeding in cirrhotic patients.

PMID- 8566850
TI  - Faecal stream diversion in patients with collagenous colitis.

PMID- 8566851
TI  - Helicobacter pylori reinfection.

PMID- 8566852
TI  - Gastric emptying in patients with insulin dependent diabetes mellitus.

PMID- 8566853
TI  - Helicobacter pylori increases proliferation of gastric epithelial cells.
AB  - The direct and indirect effects of helicobacter pylori on cell kinetics of
      gastric epithelial cell line AGS were investigated by flow cytometric analysis of
      Ki-67 positive cells and by MTT assay. Flow cytometric analysis of Ki-67
      positivity permits detection of cells that are in S-phase, whereas the MTT assay
      is a colometric measure of the number of viable cells. In the absence of added
      stimulants, 23.06 (4.88)% mean (SD) of AGS cells were Ki-67 positive. When cells
      were preincubated in the presence of H pylori, there was a significant increase
      in Ki-67 positivity (66.20 (7.89)%, p < 0.001). This increase was not seen in
      cells cultured in the presence of Campylobacter jejuni (24.63 (8.11)% or
      Escherichia coli (21.66 (9.78)%). Pre-incubation of AGS cells with supernatants
      from both H pylori and mitogen activated peripheral blood lymphocytes also
      increased the per cent of cells that were Ki-67 positive (72.93 (8.68) and 69.96
      (12.35)%; p, 0.001) respectively. Similar results were also found in MTT assay.
      These data show that both H pylori directly and the immune/inflammatory response
      to H pylori indirectly can influence the rate of epithelial cell proliferation,
      suggesting this bacterium may be an initiating step in gastric carcinogenesis and
      an important co-carcinogenic factor in H pylori positive subjects.

PMID- 8566854
TI  - Relation between gastric emptying rate and rate of intraluminal lipolysis.
AB  - The variable gastric emptying rate of a test meal is one of the major problems in
      evaluating accurately gastrointestinal physiological functions beyond the
      stomach. The aim of this study was to evaluate the effect of the gastric emptying
      rate on the rate of intraluminal lipolysis. Thirty four subjects without
      pancreatic disease (21 with a normal gastric emptying and 13 with a known slow
      gastric emptying) and 14 subjects with pancreatic disease (four without and 10
      with pancreatic insufficiency) were studied using a dual labelled breath test.
      The test meal consisted of one egg, 60 grams of white bread, 10 grams of
      margarine, and 150 ml of water (350 kcal). The egg yolk was labelled with 91 mg
      of 13C-octanoic acid, the margarine was labelled with 296 kBq of distearyl-2-14C
      octanoyl-glycerol. Breath samples were taken every 15 minutes during six hours
      and analysed for 13CO2 and 14CO2 content. The gastric emptying rate of the meal
      was evaluated by the gastric emptying coefficient, the half emptying time, and
      the lag phase; the rate of intraluminal lipolysis was evaluated by the six hours
      cumulative 14CO2 excretion. Despite a clear distinction in the rate of
      intraluminal lipolysis, no difference could be detected in gastric emptying rate
      of the test meal between subjects without and with pancreatic disease. In
      subjects with pancreatic insufficiency, intraluminal hydrolysis was the rate
      limiting process in fat assimilation; in patients without pancreatic
      insufficiency, however, gastric emptying could be rate limiting. Therefore,
      patients with known slow gastric emptying, displayed a significantly decreased
      rate of intraluminal lipolysis compared with normal controls. This decrease could
      be corrected for accurately using a correction factor based on the gastric
      emptying coefficient. In conclusion, the combined 13C-octanoic acid and 14C-mixed
      triglyceride breath test permits the measurement of gastric emptying rate and
      intraluminal lipolysis simultaneously in a minimally invasive way. Correction of
      intraluminal lipolysis rate for gastric emptying rate of the given test meal
      permits evaluation of fat assimilation rates in a physiological way regardless of
      gastric emptying disorders.

PMID- 8566855
TI  - Oral administration of protease inhibits enterotoxigenic Escherichia coli
      receptor activity in piglet small intestine.
AB  - The virulence of enterotoxigenic Escherichia coli (ETEC) is attributed to their
      ability to adhere via fimbrial adhesins to specific receptors located on the
      intestinal mucosa. A novel approach to preventing ETEC induced diarrhoea would be
      to prevent attachment of ETEC to intestine by proteolytically modifying the
      receptor attachment sites. This study aimed to examine the effect of bromelain, a
      proteolytic extract obtained from pineapple stems, on ETEC receptor activity in
      porcine small intestine. Bromelain was administered orally to piglets and K88+
      ETEC attachment to small intestine was measured at 50 cm intervals using an
      enzyme immunoassay. K88+ ETEC attachment to intestinal sections that were not
      treated with bromelain varied appreciably between sampling sites. Variability in
      receptor activity along the intestinal surface is though to be caused by the
      localised effects of endogenous proteases. Oral administration of exogenous
      protease inhibited K88+ ETEC attachment to pig small intestine in a dose
      dependent manner (p < 0.05). Attachment of K88+ ETEC was negligible after
      treatment, resembling the levels of attachment of K88 to piglets of the
      genetically determined non-adhesive phenotype, which are resistant to K88+ ETEC
      infection. Serum biochemical analysis and histopathological examination of
      treated piglets showed no adverse effects of the bromelain treatment. It is
      concluded that administration of bromelain can inhibit ETEC receptor activity in
      vivo and may therefore be useful for prevention of K88+ ETEC induced diarrhoea.

PMID- 8566857
TI  - Osmotic diarrhoea and skeletal muscle protein synthesis in vivo.
AB  - The pathogenic nature of the wasting seen in diarrhoea is unknown. This study
      measured protein synthesis in an established model of diarrhoea using lactose for
      seven days. Comparisons were also made with data obtained from rats fed an
      identical diet in which lactose was replaced by isocaloric glucose ad libitum
      (that is, the control diet). To account for diarrhoea induced anorexia, a third
      group of rats were included, which were fed identical amounts of the control diet
      as the rats with diarrhoea inducing diet. Comparisons of the diarrhoea induced
      group with rats fed the control diet ad libitum showed that diarrhoea caused a
      significant reduction in body weights. Type I and type II muscles showed
      significant reductions in protein, RNA, and DNA contents, as well as a fall in
      the derived parameters, RNA/DNA, protein/DNA, and RNA/protein. Fractional rates
      of protein synthesis (ks) were also reduced. However, synthesis rates of type I
      and II muscles relative to RNA (kRNA) were unchanged in these muscles in
      diarrhoea induced rats compared with ad libitum fed controls. In the jejunum
      there was an increase in the RNA/DNA ratio, and reductions in ks and kRNA.
      Comparisons were also made between rats with diarrhoea and rats pair fed the
      control diet. There were no changes in total muscle protein, RNA or DNA contents.
      This suggests that an important feature of body wasting in diarrhoea is the
      element of anorexia, which induces severe metabolic changes. The comparison
      between rats with diarrhoea and the pair fed group showed that histological
      features of the plantaris were not overtly changed, though diarrhoea caused
      significant reductions in RNA/DNA, protein/DNA, ks, and kRNA. Similar changes
      were seen for the soleus; though the reduction in ks failed to attain statistical
      significance. In the jejunum a comparison of diarrhoea induced rats with pair fed
      controls, showed increases in the ratios of RNA/DNA and protein/DNA.

PMID- 8566858
TI  - Polyamine metabolism of enterocyte-like Caco-2 cells after exposure to Phaseolus
      vulgaris lectin.
AB  - The effect of Phaseolus vulgaris isolectin E4 on polyamine concentrations and
      ornithine decarboxylase activity of proliferating and differentiating Caco-2
      cells was investigated. Values of putrescine, spermidine, and spermine in control
      cells were highest during the early phase of proliferative cell growth and lowest
      in the stationary phase. Phytohaemagglutinin E4 significantly increased cellular
      polyamine values during the late proliferative phase of cell growth. Ornithine
      decarboxylase activity was high during intensive proliferation and growth, but
      was lower when proliferation slowed down or ceased. Exposure of Caco-2 cells in
      the early proliferative phase of cell growth to increasing concentrations of the
      potent intestinal growth factor phytohaemagglutinin E4 greatly stimulated enzyme
      activity. In contrast, the activity of ornithine decarboxylase was not stimulated
      in Caco-2 cells of the late proliferative phase nor was there any increase in the
      enzyme activity in differentiating and fully differentiated cells of the
      stationary phase. Accordingly, when proliferating Caco-2 cells possessed the
      highest ornithine decarboxylase activity, the polyamine values were also at their
      highest. During differentiation, as the ornithine decarboxylase activity fell
      close to zero, polyamine values also decreased. In the early proliferative phase
      of cell growth ornithine decarboxylase activity coincided with DNA synthesis in
      cells exposed to Phaseolus vulgaris isolectin E4. These findings with Caco-2
      cells were similar to those found in brush border cells of the rat small
      intestine.

PMID- 8566856
TI  - Positive somatostatin receptor scintigraphy correlates with the presence of
      somatostatin receptor subtype 2.
AB  - Somatostatin receptor scintigraphy (SRS) is positive in approximately 75% of all
      patients with neuroendocrine gastroenteropancreatic tumours. This study aimed to
      identify specific somatostatin receptor (sstr) subtypes, which are responsible
      for the in vivo binding of the widely used somatostatin analogue, octreotide in
      human neuroendocrine gastroenteropancreatic tumours. Twelve patients underwent
      SRS with radiolabelled octreotide. After surgical resection, tumour tissues were
      analysed in vitro for somatostatin and octreotide binding sites by
      autoradiography. In addition, for the first time, sstr subtype mRNA expression
      was examined by semiquantitative reverse transcription polymerase chain reaction
      (RT-PCR). Tumour tissues from all SRS positive patients were positive by
      autoradiography. Semiquantitative RT-PCR revealed most prominently sstr2
      expression in scintigraphically positive tumours. Two SRS negative tumours
      contained in vitro octreotide binding sites as well as high levels of sstr1 and
      sstr2 mRNAs. Positive SRS is mainly due to sstr2. sstr1, 3, 4, and probably 5 are
      less important for in vivo octreotide binding. False negative scintigraphic
      results seem to be influenced by factors independent of the expression of
      specific sstr.

PMID- 8566859
TI  - In vitro contractile effects of short chain fatty acids in the rat terminal
      ileum.
AB  - Short chain fatty acids (SCFAs), produced in the gut by bacterial fermentation of
      carbohydrates, change intestinal motility by mechanisms as yet unknown. This
      study examined the mechanism(s) of action of SCFAs on contractility using
      isolated rat terminal ileum segments and isolated ileal smooth muscle cells.
      Strip contractions were recorded under isometric conditions. Intracellular
      calcium concentration ([Ca2+]i) was measured in single cells loaded with indo-1
      penta-acetoxymethyl ester (indo-1 AM). SCFAs (10(-9) to 10(-2) mol/l) induced
      concentration dependent contractions. The effect was not different among the
      individual SCFAs. Exogenous acids (namely tartaric and citric acids) caused
      similar responses as SCFAs, whereas sodium acetate had no effect. The contraction
      was not blocked by tetrodotoxin, atropine or hexamethonium, showing that it was
      not mediated through a cholinergic pathway. Moreover, removal of the mucosa or
      addition of procaine (a local anaesthetic) to the bath did not change the SCFA
      induced contraction, while verapamil (a calcium-channel antagonist) completely
      suppressed it. In addition, application of SCFAs to isolated ileal myocytes
      evoked peaks in [Ca2+]i inhibited by D 600 (a blocker of voltage dependent
      calcium channels). Taken together, these results suggest that the contractile
      response stimulated by SCFAs in the rat terminal ileum could result from an acid
      sensitive calcium dependent myogenic mechanism.

PMID- 8566860
TI  - Calcium in milk and fermentation by yoghurt bacteria increase the resistance of
      rats to Salmonella infection.
AB  - Calcium in milk products stimulates gastric acid secretion and inhibits the
      cytolytic activity of intestinal contents. Based on these effects, it was
      hypothesised that calcium might lessen the severity of food borne intestinal
      infections. The possible differential effects of a low calcium milk and normal
      milk products (milk, acidified milk, and pasteurised yoghurt) on the resistance
      of rats to a salmonella infection was therefore studied. Rats were infected
      orally with Salmonella enteritidis just after food consumption. The first day
      after infection, faecal salmonella counts of the yoghurt fed rats were
      significantly lower than those of the other groups. Thereafter, faecal salmonella
      excretion declined rapidly in all high calcium groups, whereas rats fed the low
      calcium milk continued to excrete high numbers of salmonella. The reduced
      colonisation resistance to salmonella of rats fed low calcium milk might be
      caused by the high cytolytic activity of faecal water or a high iron
      concentration in faecal water, already present before infection, or both. The
      reduced resistance of these rats corresponded with a large infection induced
      increase in the cytolytic activity of faecal water, an appreciable reduction in
      apparent iron absorption, and a large increase in faecal mucin and alkaline
      phosphatase excretion. In yoghurt fed rats, only minor infection induced changes
      in luminal parameters were noticed. The rats fed milk and acidified milk always
      showed intermediate reactions. In conclusion, in addition to fermentation by
      yoghurt bacteria, calcium in milk products strongly enhanced the resistance to
      salmonella infection by lowering luminal cytolytic activity or diminishing the
      availability of iron for pathogen growth, or both.

PMID- 8566861
TI  - Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.
AB  - The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of
      proximal duodenal mucosal bicarbonate secretion than previously reported using an
      H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions
      were performed in healthy volunteers to evaluate whether this incidental finding
      is explained by more potent gastric acid inhibition by omeprazole or might be
      caused by the different mode of drug action. Basal and stimulated gastric and
      duodenal bicarbonate secretion rates were measured in the same subjects in
      control experiments (n = 17) and after pretreatment with high dose omeprazole (n
      = 17) and ranitidine (n = 9), respectively, by use of a technique permitting
      simultaneous measurements. Concentrations of bicarbonate were measured in the
      respective effluents by the method of back titration. Both omeprazole and
      ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05).
      Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39)
      mumol/h; p < 0.02) and vagally stimulated (834 (72) v 474 (66) mumol/h; p <
      0.02), but not acid stimulated (3351 (678) v 2550 (456) mumol/h; p > 0.05)
      duodenal bicarbonate secretion compared with control experiments. Also the
      combination of omeprazole and ranitidine increased (p = 0.05) duodenal
      bicarbonate secretion, while ranitidine alone caused no change in either basal or
      stimulated secretion. In the stomach basal as well as vagally stimulated
      bicarbonate secretion was independent of the means of acid inhibition. These
      results show that the proton pump inhibitor, omeprazole, promotes proximal
      duodenal mucosal bicarbonate secretion apparently independent of its gastric acid
      inhibitory effect. The mechanism of action remains speculative.

PMID- 8566862
TI  - Elongation factor 1 gamma mRNA expression in oesophageal carcinoma.
AB  - Elongation factor 1 gamma (EF1 gamma) is known to be a subunit of EF1, one of the
      G proteins that mediate the transport of aminoacyl tRNA to 80S ribosomes during
      translation. As little is known regarding the expression of EF1 gamma in human
      oesophageal carcinoma, this study looked at its expression using a northern blot
      analysis. Thirty six cases of oesophageal carcinoma and 15 oesophageal carcinoma
      cell lines were studied. The EF1 gamma mRNA overexpression at a level of twofold
      or more was seen in five (14%) of 36 carcinomatous tissues compared with the
      normal counterparts. All five overexpressed cases showed severe lymph node
      metastases compared with the non-overexpressed cases, and the difference was
      significant (p = 0.028). The stage of the disease of these five cases was far
      advanced compared with the nonoverexpressed cases (p = 0.012). All 15 oesophageal
      carcinoma cells expressed EF1 gamma mRNA relatively lower than the gastric or
      pancreatic carcinoma cell lines, in which EF1 gamma was originally isolated. As
      the expression of EF1 gamma mRNA could be detected even in the biopsy specimens,
      its overexpression in tumour tissue may provide preoperative useful information
      for predicting the aggressiveness of tumours.

PMID- 8566863
TI  - Mucosal ablation using photodynamic therapy for the treatment of dysplasia: an
      experimental study in the normal rat stomach.
AB  - Surgery is the only effective treatment for dysplasia in the gastrointestinal
      tract with considerable associated morbidity and mortality and is difficult to
      justify without confirmed malignancy. Photodynamic therapy (PDT) produces
      localised necrosis, which can be limited to the mucosa. This study examined the
      mechanical properties of the normal rat stomach after PDT. The aim of this study
      was to measure the bursting pressure of PDT lesions in the stomach and to assess
      gastric emptying after producing circumferential mucosal necrosis at the pylorus
      by PDT. Two photosensitising agents were used--5-aminolaevulinic acid (ALA), and
      aluminium disulphonated phthalocyanine (A1S2Pc). Normal rats were sensitised and
      PDT lesions created in the stomach with red light. The bursting pressure was
      measured and compared with that in thermal control lesions. In further
      experiments, circumferential mucosal necrosis was produced at the pylorus, and
      animals observed for subsequent eating and weight gain. It was found that gastric
      bursting pressure was reduced after thermal injury, but not at any time after PDT
      (with A1S2Pc, but not ALA, adhesive omental reinforcement was required to
      maintain the gastric wall strength at one week). For the pyloric lesions, gastric
      emptying was permanently impaired using A1S2Pc, but with low dose ALA (20 mg/kg)
      had returned to normal by three days. With ALA, but not A1S2Pc, necrosis could be
      limited to the mucosa. In conclusion, using ALA, selective ablation of the
      gastric mucosa is possible, which does not reduce the strength of the stomach and
      only temporarily delays gastric emptying. PDT is a promising technique for the
      circumferential ablation of dysplastic mucosa.

PMID- 8566864
TI  - Cyclooxygenase-1 and cyclooxygenase-2 gene expression in human colorectal
      adenocarcinomas and in azoxymethane induced colonic tumours in rats.
AB  - Increased prostaglandin E2 synthesis is considered important in both human and
      experimental colon carcinogenesis. It is not known, however, which cyclooxygenase
      isoenzyme is involved. The aim of this study was to compare the content of mRNA
      for cyclooxygenase-1 and cyclooxygenase-2 in colorectal cancers with the content
      in normal colonic specimens. Fifteen human colorectal adenocarcinomas, 35
      azoxymethane induced colonic tumours from rats, and specimens of normal colon
      were analysed by reverse transcription and polymerase chain reaction (RT-PCR). It
      was found that cyclooxygenase-1 and cyclooxygenase-2 mRNA were increased in
      azoxymethane induced colonic tumours, compared with specimens taken adjacent to
      the tumours or from the macroscopically normal intestine distant from the
      tumours. Cyclooxygenase-1 and cyclooxygenase-2 mRNA were increased in specimens
      from the macroscopically normal intestine of azoxymethane treated animals,
      compared with colonic specimens from saline treated rats. Cyclooxygenase-2 mRNA,
      but not cyclooxygenase-1 mRNA, was increased in human colorectal cancers,
      compared with the adjacent mucosa or macroscopically normal mucosa distant from
      the tumours. The results suggest that cyclooxygenase-2 is involved in the
      increased prostaglandin E2 synthesis in colonic cancers, and that activation of
      this isoenzyme is an early event in colon carcinogenesis. However, cyclooxygenase
      1 may also be involved, at least in experimental colon carcinogenesis.

PMID- 8566865
TI  - Lymphocyte subset infiltration patterns and HLA antigen status in colorectal
      carcinomas and adenomas.
AB  - Fifty eight large bowel adenocarcinomas and 20 adenomas were studied
      immunohistochemically, using fresh frozen tissue sections, with regard to
      lymphocyte subpopulations (CD3, CD4, CD8, CD19, and CD20) in the inflammatory
      infiltrate and to expression of human leucocyte antigens (HLA-ABC, HLA-A2, and
      HLA-DR). The findings were related to differentiation and Duke's stage of
      carcinoma. The inflammatory infiltrate was found to have a phenotype that
      remained constant irrespective of the intensity of the inflammation. CD4 and CD3
      positive cells predominated with fewer CD8 positive cells and a scanty diffuse
      CD19/20 positive cell population. CD19/20 follicular aggregates were common at
      the advancing margin of the carcinomas. There was no significant association with
      Duke's stage, differentiation or HLA status. HLA changes (ABC loss, A2 loss, and
      DR gain) were associated with differentiation, being more common and more
      extensive in poorly differentiated carcinomas. HLA-A2 loss was also associated
      with stage of progression of carcinoma. Inflammation associated with adenomas was
      found to have a similar phenotype to that associated with carcinomas. HLA changes
      in adenomas were uncommon, being seen in only one of our 20 cases.

PMID- 8566866
TI  - Interleukin 8: cells of origin in inflammatory bowel disease.
AB  - Neutrophils are important cellular mediators in inflammatory bowel disease (IBD).
      Interleukin (IL)8, a powerful neutrophil chemoattractant, is found in increased
      quantities in inflamed mucosa, but the cells of origin are uncertain. IL8 gene
      expression was studied by in situ hybridisation in uninflamed intestinal tissue
      resected for colon carcinoma (n = 7) and in inflamed colonic tissue resected for
      IBD (n = 11). Immunohistochemistry was used to assess the phenotype of IL8
      expressing macrophages and the production of IL8 protein. Macrophages isolated
      from intestinal resections and lipopolysaccharide stimulated peripheral blood
      monocytes treated with 5-aminosalicylic acid, hydrocortisone, and cyclosporin A
      were examined for IL8 mRNA by northern blotting and IL8 secretion by enzyme
      linked immunosorbent assay (ELISA). In all cases IL8 mRNA was detected by in situ
      hybridisation in macrophages and neutrophils adjacent to ulceration in inflamed
      bowel, but not detected in uninflamed mucosa from carcinoma resections. Recently
      recruited CD14 positive macrophages were responsible for some of this IL8
      expression. IL8 protein was present in the same distribution as mRNA. Epithelial
      cells in normal and inflamed tissue showed neither mRNA nor protein. IL8 mRNA was
      expressed significantly more commonly by macrophages from IBD affected than from
      normal mucosa, and IL8 secretion by IBD but not normal colon macrophages was
      augmented significantly by lipopolysaccharide treatment. IL8 expression and
      production by lipopolysaccharide treated blood monocytes was inhibited by the
      therapeutic agents tested. These results show that neutrophils and recently
      recruited macrophages are responsible for production of IL8 in IBD, suggesting a
      mechanism for a continuing cycle of neutrophil attraction. Agents used
      therapeutically in these diseases may be effective in part by disrupting this
      cycle.

PMID- 8566867
TI  - Microalbuminuria correlates with intestinal histopathological grading in patients
      with inflammatory bowel disease.
AB  - It has previously been shown that microalbuminuria is a useful disease activity
      marker for inflammatory bowel disease (IBD). Microalbuminuria correlates strongly
      with the markers of clinical and laboratory disease activity such as erythrocyte
      sedimentation rate (ESR), and C reactive protein (CRP). The aim of this study was
      to discover if microalbuminuria accurately reflects the intestinal inflammation
      by correlating it with intestinal inflammation using a standard histopathological
      grading system in patients with ulcerative colitis and Crohn's colitis. Forty two
      patients with IBD who had undergone endoscopic examination of the entire colon
      for the assessment of severity and extent of the disease (Crohn's colitis (n =
      21), ulcerative colitis (n = 21)) were recruited to the study. Patients with
      small bowel Crohn's disease were not studied. Twenty four patients had left sided
      colonic disease and 18 patients had extensive colonic disease. Each patient's
      colonic biopsy specimens were scored blindly by a histopathologist and a
      composite score was compiled on the basis of the severity of changes in the
      enterocytes and crypts and the cellularity of the lamina propria. A clinical
      disease activity was obtained using the simple index of Harvey and Bradshaw.
      Microalbuminuria was measured in all patients by an immunoturbiditimetric method.
      ESR and CRP were also measured, as indicators of acute phase response in the same
      patients. It was found that patients with active IBD had higher concentrations of
      microalbuminuria compared with those patients in remission (median 222
      micrograms/min (range 40-686 micrograms/min) v median 96 micrograms/min (range 30
      376 micrograms/min); p < 0.001)). Significantly higher concentrations of
      microalbuminuria were also detected in patients with extensive colonic IBD
      compared with those patients with left sided disease (median 297 micrograms/min
      (range 132-686 micrograms/min) v median 101 micrograms/min (range 30-433
      micrograms/min); p < 0.001)). A strong positive correlation was seen between
      microalbuminuria and intestinal histopathological score in IBD patient groups
      with left sided colitis (r = 0.77; p < 0.001) and extensive disease (r = 0.71; p
      < 0.01). The standard histopathological grading system correlated with the
      clinical disease activity (r = 0.64; p < 0.005) and CRP (r = 0.62; p < 0.02),
      however, it did not correlate with ESR. In conclusion, the strong correlation of
      microalbuminuria with a standard intestinal histopathological grading system
      suggests that microalbuminuria accurately reflects the severity of colonic
      inflammation in patients with Crohn's colitis and ulcerative colitis.

PMID- 8566868
TI  - [Conservative hemotherapy. Blood component therapy instead of whole blood
      transfusion and homologous blood saving methods].

PMID- 8566869
TI  - [Psychiatry and gynecology].

PMID- 8566870
TI  - [Psychiatric emergencies and crises in gynecology].

PMID- 8566871
TI  - [Surgical management of psychiatrically ill patients. Particular aspects of
      perioperative monitoring].

PMID- 8566872
TI  - [Psychiatric manifestations in climacteric. Diagnostic difficulties and
      therapeutic possibilities].

PMID- 8566873
TI  - [Sex differences in schizophrenia].

PMID- 8566874
TI  - [Psychiatric diseases with onset in puerperium].

PMID- 8566875
TI  - [Psychiatric diseases and pregnancy].

PMID- 8566876
TI  - [Self-injury behavior].

PMID- 8566877
TI  - [Sterilization of mentally handicapped patients].

PMID- 8566878
TI  - Iron overload in thalassemia: comparative analysis of magnetic resonance imaging,
      serum ferritin and iron content of the liver.
AB  - BACKGROUND: Iron overload in patients with thalassemia is a common feature which
      requires continuous chelation therapy and monitoring. Serum ferritin
      determination is widely accepted as a simple method for following iron load in
      patients with primary hemochromatosis; however, several reports on thalassemic
      patients emphasize that ferritinemia is not accurate and that other methods such
      as direct measurement of iron in the liver (HIC) and magnetic resonance imaging
      (MRI) are more precise. MATERIALS AND METHODS: In order to contribute to the
      general understanding of iron load in thalassemia we used liver MRI to study 33
      thalassemic patients, most of whom were also evaluated for iron content by liver
      biopsy. The data were then compared with serum ferritin levels. RESULTS: Ferritin
      levels ranged between 276 and 8031 ng/mL, and liver iron content ranged from 1.6
      to 31.0 mg/g dry weight; grade III or IV liver siderosis was recorded in 23/33
      patients, just as 23/33 patients were found to have severe or very severe
      siderosis at MRI. Significant correlations with ferritin levels were recorded
      between grade IV and grades III, II and I (p < 0.01, p = 0.02, and p = 0.03,
      respectively). Ferritinemia also showed significant linearity with liver iron
      content (r = 0.603, p = 0.001). No significant differences of levels were
      recorded, however, between patients found to have severe and those with mild iron
      load at MRI (p = 0.073). CONCLUSIONS: Our study shows that serum ferritin levels
      exhibit a tendency to be significantly correlated with the true status of
      hemochromatosis in thalassemic patients; however, the discrepancies recorded in
      several patients and the scarce or total lack of correlation with MRI suggest
      exploring other approaches to this problem in order to make proper decisions
      about therapy.

PMID- 8566879
TI  - Epidemiology of acute promyelocytic leukemia.
AB  - BACKGROUND: The estimated incidence of acute promyelocytic leukemia (APL) is
      approximately 6 cases per 10 million people per year with no apparent differences
      between sexes. The age of APL cases is younger than that of other acute myeloid
      leukemias (AML). Spatial and temporal clusters of APL have been reported. These
      observations suggest a possible selective role for environmental and/or
      occupational factors in APL development. METHODS: A multicenter case-control
      study was carried out on risk factors for acute leukemias and preleukemias. In
      this report data related to APL are selectively analyzed from the larger study to
      identify specific risk factors. RESULTS: The case-control study on 38 cases of
      APL showed a strong association with shoemaking (odds ration 6.3, 95% confidence
      interval 1.3-31.1). A moderate leukemogenic effect from living in houses built
      with tuff, a polous building material containing gamma-emitting radionuclides and
      having a high radon concentration, and from using hair dyes was also suggested.
      CONCLUSIONS: These data, together with the reported spatial and temporal
      clustering of APL, support the hypothesis of specific environmental and/or
      occupational risk factors for APL among other AML subtypes and indicate the need
      for additional ad hoc multicenter studies.

PMID- 8566880
TI  - Diagnostic approach to and follow-up of difficult cases of AL amyloidosis.
AB  - BACKGROUND: Routine electrophoretic analysis fails to detect a monoclonal
      component (MC) in a considerable portion of AL amyloidosis patients. We
      investigated whether the combination of immunofixation (IF) on agarose gel
      electrophoresis and bone marrow plasma cell (BMPC) light chain kappa/lambda ratio
      analysis could contribute to diagnosis in these cases. The possible use of the
      BMPC kappa/lambda ratio in monitoring the clone was also investigated. METHODS:
      We performed BMPC kappa/lambda ratio analysis and IF of serum and urine in 16
      selected patients with no detectable MC at routine analysis, despite clinical
      features suggestive of primary amyloidosis. An anti-idiotypic monoclonal antibody
      specific for the amyloidogenic immunoglobulin and the BMPC kappa/lambda ratio
      were used to monitor the clone in a patient who underwent autologous peripheral
      blood stem cell transplantation. RESULTS: Abnormal kappa/lambda ratios were found
      in 14 (sensitivity 87.5%), and a MC in 12 (sensitivity 75%). Combination of the
      two analyses confirmed diagnosis in all cases. In one patient changes in the size
      of the clone, monitored on serial bone marrow aspirates by an anti-idiotypic
      antibody, paralleled variations of the kappa/lambda ratio. CONCLUSIONS: This
      study demonstrates that the combined use of IF and the BMPC kappa/lambda ratio is
      extremely powerful in AL amyloidosis. In addition, the BMPC kappa/lambda ratio
      should be considered for monitoring the amyloidogenic clone when serum or urine
      MC is not quantifiable.

PMID- 8566882
TI  - Prostaglandin E2 bladder instillation for the treatment of hemorrhagic cystitis
      after allogeneic bone marrow transplantation.
AB  - BACKGROUND: Hemorrhagic cystitis (HC) is a major complication of high-dose
      cyclophosphamide therapy used in the preparative regimen for allogeneic or
      autologous bone marrow transplantation. Several viruses (adenovirus,
      cytomegalovirus and polyomavirus BK) have also been implicated in the etiology of
      HC. No one established method of treatment is as yet available. MATERIALS AND
      METHODS: HC developed in 10 patients after allogeneic bone marrow transplantation
      and was BK viruria-associated in all cases. All patients were treated with
      instillations of prostaglandin E2 (PGE2) directly into the bladder. RESULTS: A
      complete resolution of hematuria within a short time (5 +/- 1 days) was observed
      in all cases; in 4/10 patients urine cleared within 24 hours of the initial
      treatment. Intravesical PGE2 therapy caused no systemic circulatory or
      respiratory problems, although bladder spasms occurred in all patients.
      CONCLUSIONS: Intravesical prostaglandin E2 instillation appears to be an
      effective treatment for hemorrhagic cystitis in bone marrow transplant patients;
      further studies are required to assess the actual role of BK virus in the
      pathogenesis of HC in bone marrow transplant patients.

PMID- 8566881
TI  - A randomized, double-blind, cross-over study comparing a levosulpiride-based and
      a metoclopramide-based combination in the prevention of ProMECE-CytaBOM-induced
      emesis.
AB  - BACKGROUND: To test two different antiemetic regimens for preventing nausea and
      vomiting in patient with non-Hodgkin's lymphoma (NHL) undergoing systemic
      chemotherapy (CT) with ProMECE-CytaBOM (P-C). PATIENTS AND METHODS: Twenty
      consecutive untreated adult outpatients with histologically confirmed NHL and
      scheduled to receive P-C chemotherapy were registered in a randomized, double
      blind, cross-over study to compare the antiemetic efficacy of a levosulpiride
      (LS)-based and metoclopramide (MTC)-based regimen. RESULTS: Complete protection
      from vomiting was recorded in 93% (62/67) of courses with the LS-regimen and in
      89% (62/70) with the MTC-regimen (p = 0.428). No nausea was observed in 84%
      (56/67) of courses with the LS-regimen and in 74% (52/70) with the MTC-regimen (p
      = 0.183). No differences in prevention of emesis were recorded when patients
      crossed to the other regimen. Both regimens were well tolerated; however, on day
      8 of chemotherapy, when both antiemetic regimens were administered at a higher
      dose, the LS-based combination showed significantly lower toxicity (p = 0.035).
      CONCLUSIONS: ProMECE-CytaBOM-induced emesis can be prevented in most cases with
      appropriate, specifically designed antiemetic therapy. Both the LS- and MTC-based
      combinations resulted in a high percentage of complete protection from emesis,
      but the higher incidence of side effects observed with MTC makes the LS-based
      regimen preferable for patients receiving P-C chemotherapy.

PMID- 8566883
TI  - Performance characteristics of Hemox-Analyzer for assessment of the hemoglobin
      dissociation curve.
AB  - The Hemox-Analyzer (TCS, Medical Products Division, Southampton, PA) is an
      automatic system for determining the oxyhemoglobin dissociation curve (ODC) and
      P50 values. The ODC is recorded during deoxygenation with nitrogen gas and
      plotted on graph paper; the oxygen tension is detected by a Clark electrode,
      while the oxyhemoglobin fraction (%HbO2) is evaluated by a dual-wavelength
      spectrophotometer. Even though this instrument has been commercially available
      for more than 20 years, its performance characteristics have been assessed. We
      evaluated the performance characteristics of the Hemox-Analyzer. P50 was tested
      in 28 healthy volunteers, in 16 anemic and in 9 polycythemic patients. To test
      its precision we evaluated both inter- and intra-assay variability. The system
      shows good precision: standard deviation was 0.39 for assays in duplicate, CV =
      1.9% for intra-assay and CV = 3.0% for inter-assay measurements. The mean P50
      values were 25.2 +/- 1.5 mmHg in normal volunteers and 27.3 +/- 1.4 mmHg in
      anemic patients. The Hemox-Analyzer is a simple, quick and reliable instrument
      for recording the oxyhemoglobin dissociation curve. Both the P50 value and
      observation of the fine structure of the curve can furnish information about the
      delivery of oxygen to tissues.

PMID- 8566884
TI  - Serum interleukin-8 levels in thalassemia intermedia.
AB  - In this study we determined serum IL-8 levels in 18 untransfused patients with
      beta-thalassemia intermedia and in 14 subjects affected by HbH disease. As
      reported in polytransfused homozygous beta-thalassemia, untransfused beta
      thalassemia and HbH disease show significantly (p < 0.005) higher serum IL-8
      levels than normal controls. Our data suggests that there could be an intrinsic
      cause for the IL-8 increase in thalassemia intermedia. We think than the
      hyperactivity of thalassemic macrophages related to chronic hemolysis is the main
      cause for the increment in cytokines, such as IL-8, found in thalassemic
      syndromes.

PMID- 8566885
TI  - Trisomy 13 in a case of myelofibrosis with myeloid metaplasia with early blastic
      transformation.
AB  - We describe a case of early myeloid blastic transformation in a 64-year-old man
      suffering from myelofibrosis with myeloid metaplasia. Both chronic and blastic
      phase cytogenetic analysis showed trisomy 13 to be the sole chromosome
      aberration. A potential role for this rare abnormality in determining such an
      unusually poor clinical outcome is discussed.

PMID- 8566886
TI  - 5q- in a case of chronic myelogenous leukemia relapsed after allogeneic bone
      marrow transplantation.
AB  - Clonal chromosome and/or hematological abnormalities typically observed in
      myelodysplastic syndromes (MDS) have been described with increased frequency
      after autologous bone marrow transplantation (BMT) for lymphoma. We report the
      case of a woman with chronic myelogenous leukemia (CML) allografted with her HLA
      identical sibling who, 5 years after the transplant and under immunosuppressive
      treatment for chronic graft host disease (GVHD), suffered a cytogenetic relapse
      associated with a 5q- deletion in the host metaphases. These findings suggest
      that myelodysplastic changes, possibly related to the chemo-radiotherapy
      conditioning regimen, may also present after allogeneic BMT.

PMID- 8566887
TI  - Study of CD40 ligand expression in B-cell chronic lymphocytic leukemia.
AB  - CD40 ligand (CD40L) is a membrane molecule that plays a key role in T cell-B cell
      cooperation, providing B cells the helper signals needed for activation,
      proliferation, differentiation and prevention of apoptosis. Patients with B-cell
      chronic lymphocytic leukemia (B-CLL) were studied to verify the following
      hypotheses: a) whether defective CD40L expression on activated T cells could
      account for deficient helper signals and therefore for hypogammaglobulinemia; b)
      whether aberrant CD40L expression on B cells could be a mechanism by which
      leukemic cells stimulate themselves via CD40 to escape apoptosis. Results showed
      physiological expression of CD40L on in vitro activated CD4+ cells, while this
      expression was absent on fresh and activated B cells. Abnormalities in CD40/CD40L
      interaction do not seem to play a role either in the pathogenesis of
      hypogammaglobulinemia or in lymphocyte accumulation in B-CLL.

PMID- 8566888
TI  - Autologous bone marrow transplantation in non-Hodgkin's lymphomas: prediction of
      mononuclear cell yield in bone marrow harvests.
AB  - We retrospectively analyzed the factors influencing the mononuclear cell (MNC)
      yield on bone marrow (BM) harvests in a cohort of 15 non-Hodgkin's lymphoma
      patients undergoing autologous bone marrow transplantation. All the patients were
      treated with the F-MACHOP regimen and four of them also received radiotherapy on
      bulky disease. Before harvesting, the patients underwent complete peripheral
      blood (PB) count, BM biopsy and aspirate. WBC and MNC/microL were determined on
      the pre-harvest PB and BM aspirate samples using an automated counter. The
      following variables were examined in univariate and multivariate regression
      analysis for possible influence on the MNC yield in the harvests: age, sex,
      number of cycles of CT, previous radiotherapy, state of the disease at the time
      of harvest, interval between the end of therapy and BM harvest, cellularity of
      the BM biopsy, absolute WBC and MNC counts in the PB before harvesting, absolute
      WBC and MNC counts in the BM aspirate performed before harvesting. The amount of
      marrow harvested was constant for all patients: 21.2 +/- 0.24 microL/kg B.W.
      Among the factors analyzed, two correlated strongly with the MNC yield/kg B.W. in
      the harvests: the MNC count in pre-harvest PB (r = 0.823; p = 0.0001) and the MNC
      count in pre-harvest BM aspirate (r = 0.802; p = 0.0003). A regression equation
      was generated that allows calculation of the MNC/kg yield prior to harvesting.

PMID- 8566889
TI  - Central venous catheterization in pediatric patients affected by hematological
      malignancies.
AB  - The objective of this retrospective study was to evaluate the significance and
      complications of percutaneous central venous catheterization in pediatric
      patients affected by hematologic malignancies. One hundred and fifty-eight
      central venous catheters were inserted in 125 pediatric patients (male/female
      67/58; median age: 4 years; range 10 m - 6 y.) affected by hematological
      malignancies. Venous access was obtained by means of a tunnelled silicone rubber
      Groshong catheter inserted percutaneously in the subclavian vein (91.1%), the
      internal jugular vein or in the femoral vein. The medial duration of
      catheterization was 231.8 days (range 8-1014 days). The total number of catheter
      days was 33,792 (92.6 years). There were no complications related to catheter
      insertion. Only one patient developed significant post-operative bleeding. One
      hundred and nine catheters (68.9%) were removed when they were no longer needed
      and 49 (31.1%) were removed due to complications: 6 catheter occlusions (12.2%),
      7 were accidentally withdrawn (14.3%), 3 for local infections (6.1%) and 33 for
      catheter-related infection (67.3%). A Groshong catheter seems to provide good
      access to the blood stream for a long period of time with a low incidence of
      complications in children with acute hematological malignancies.

PMID- 8566890
TI  - Inefficacy of fresh frozen plasma in the treatment of L-asparaginase-induced
      coagulation factor deficiencies during ALL induction therapy.
AB  - A prospective longitudinal study was conducted to determine whether single-donor
      fresh frozen plasma (FFP) substitution was able to influence L-asparaginase
      associated hypoproteinemia. Within a 36-month period, 20 of 42 children with ALL
      received a total of 42 prophylactic FFP doses at a median of 10 (5-20) mliter/kg
      when fibrinogen levels decreased to < 60 mg/dL and thrombin time was lengthened.
      Laboratory monitoring before, during and after FFP substitution showed no short
      term improvements and demonstrated only a minimal increase in fibrinogen and
      alpha 2-antiplasmin. Plasma levels of antithrombin and plasminogen remained
      unchanged. Furthermore, administration of FFP had no influence on thrombin
      generation, the plasmin/alpha 2-antiplasmin complex or enhanced D-dimer
      formation.

PMID- 8566891
TI  - Molecular pathogenesis of non-Hodgkin lymphoma: a clinical perspective.
AB  - Despite a common origin from mature lymphoid cells, non-Hodgkin lymphomas (NHL)
      represent a surprisingly heterogeneous group of lymphoid malignancies whose
      classification is continuously being remodeled. The most recent proposal, the
      Revised European-American classification, introduces pathogenetic features among
      the classification criteria. In this respect, knowledge of the molecular
      pathogenesis of NHL, which is based upon genetic lesions leading to activation of
      proto-oncogenes (e.g. BCL-1, BCL-2, BCL-6, c-MYC) or disruption of tumor
      suppressor genes (e.g. p53), is becoming increasingly relevant for the clinician.
      These lesions combine into multiple molecular pathways which are selectively
      associated with distinct NHL types. Thus, for example, rearrangements of BCL-1,
      BCL-2, BCL-6, and c-MYC ar the genetic hallmarks of mantle cell, follicular,
      diffuse large cell, and Burkitt's lymphoma, respectively. Overall, from clinical
      perspective, NHL genetic lesions serve three purposes: a) they assist and
      complement histologic diagnosis; b) they provide a molecular marker with
      prognostic relevance; c) they allow evaluation of minimal residual disease
      through highly specific and highly sensitive technologies.

PMID- 8566892
TI  - Umbilical cord blood as a source of hematopoietic stem cells: from research to
      clinical application.
AB  - The clonogenic capacity of human umbilical cord blood (UCB) has been evaluated in
      several studies which found high numbers of primitive hematopoietic progenitor
      cells. Recently, UCB progenitor cells were shown to possess significant
      advantages over bone marrow (BM) in terms of proliferative capacity and
      immunologic reactivity. Therefore UCB has come to be considered an attractive
      source of hematopoietic stem cells for both research and clinical applications.
      UCB has been used in the treatment of diseases potentially curable by bone marrow
      transplantation (BMT). Seventy-one transplants have been performed world-wide
      using UCB cells, and the results have been reported to the International Cord
      Blood Transplant Registry (ICBTR). Since UCB cells appear to be less alloreactive
      than BM cells, studies have been carried out to determine the most successful
      procedures for collection and fractionation of UCB and to quantify precisely the
      progenitor/stem cell content. The different techniques for quantifying
      progenitor/stem cells as well as the results of related and unrelated UCB
      treatments will be reviewed. Further clinical applications of UCB involving gene
      therapy and stem cell expansion will be discussed.

PMID- 8566893
TI  - Hemophagocytic lymphohistiocytosis: still a morphological diagnosis.

PMID- 8566894
TI  - Extrapulmonary tuberculosis and non-Hodgkin's lymphoma: coexistence in an
      abdominal lymph node.

PMID- 8566895
TI  - Familial occurrence of IgMk gammapathy: no involvement of HCV infection.

PMID- 8566896
TI  - High prevalence of antibodies to hepatitis C virus in patients with
      lymphoproliferative disorders.

PMID- 8566897
TI  - Effect of sodium valproate on the spontaneous contractile and bioelectric
      activity of smooth muscle fibres isolated from experimental animals.
AB  - Experiments were carried out with smooth muscles preparations of 24 rats (gastric
      corpus) and 36 guinea pigs (gastric corpus and taenia coli). Their contractile
      responses were recorded isometrically using tensile transducers. The bioelectric
      activity was determined by the single sucrose-gap method. Depending on the
      concentration sodium valproate elicits two types of responses from the smooth
      muscle of gastrointestinal tract of rats and guinea pigs: a contractile response,
      at concentrations less than 10(-4) g/ml, and a relaxant response, at
      concentrations higher than 10(-4) g/ml. At concentrations below 10(-4) g/ml
      sodium valproate induces contractions of the smooth muscle taken from the rat and
      guinea pig gastrointestinal tract. These contractions can be abolished by
      indomethacin. It may be concluded, therefore, that the contractile effect of
      sodium valproate has a prostaglandin basis. At concentrations higher than 10(-4)
      g/ml, sodium valproate hyperpolarizes the smooth muscle tissues, reduces the
      frequency and amplitude of the spontaneously generated spike potentials and
      relaxes the preparations. These effects are blocked by picrotoxin. Sodium
      valproate in high concentrations increases the endogenous level of the gamma
      aminobutyric acid stimulating at the same time the prostaglandin synthesis which
      is inadequate to compensate the relaxant effect induced by elevated level of the
      endogenous gamma-aminobutyric acid.

PMID- 8566898
TI  - Tobacco smoking (up to 10 cigarettes daily) and lung functions in pregnant women.
AB  - The main objective of this paper was to study the effect of tobacco smoking (up
      to 10 cigarettes daily) on lung functions of healthy pregnant women as part of a
      large scale foetus antenatal care programme. Seventy eight pregnant women with no
      history and clinical evidence of pulmonary, cardiac, obstetrical or gynecological
      diseases were subjected to a comprehensive functional investigation of breathing.
      The women, all in the tenth lunar month of pregnancy, were divided into four
      categories: non-smokers, ex-smokers that have quitted smoking after diagnosing of
      pregnancy, with a mean of 2.0 +/- 1.2 pack-years of smoking (mean +/- SD), and
      current smokers with 3.1 +/- 1.9 pack-years of smoking. The results obtained show
      that light smoking causes no essential changes in the lung function parameters of
      pregnant women with the exception of the reduction tendency of the parameters of
      airway conductance and the strength of the respiratory muscle (PImax and PEmax).

PMID- 8566899
TI  - Studies on nephrolithiasis in patients with autosomal dominant polycystic kidney
      disease.
AB  - Eighty two patients with autosomal dominant polycystic kidney disease were
      examined clinically. Nephrolithiasis was diagnosed in 23 patients (28.1%). In 17
      (73.5%) the lithiasis was bilateral. There were no patients with nephrolithiasis
      under the age of 20 years. The disease frequency increased in the patients
      between 21 and 40 years (38.5%) reaching 58.1% in those above 41 years.
      Nephrolithiasis in autosomal dominant polycystic kidney disease is not induced by
      the chronic renal failure. The opposite is more likely-nephrolithiasis
      precipitates the onset of renal failure. The autosomal dominant polycystic kidney
      disease is an etiologic factor for lithiasis.

PMID- 8566900
TI  - Study of the effect of recombinant erythropoietin on renal anaemia in predialysis
      patients with chronic renal failure.
AB  - Recombinant erythropoietin was given to six renal anaemia patients (2 male and 4
      female, aged 38-66 years) with chronic renal failure in the predialysis state.
      Eprex (Cilag, Switzerland) was used in the treatment. The preparation was
      administered subcutaneously, thrice weekly for 6 months, at a mean dose of 50
      U/kg. The aim of the therapy was to keep haemoglobin in the target range of 100
      and 120 milligrams. No allergic reactions or other forms of intolerance to the
      preparation were noticed. The mean baseline haemoglobin level prior to treatment
      (75.5 +/- 4.06 milligrams) increased to 96.3 +/- 6.9 milligrams at three months
      and 106.0 +/- 7.1 milligrams at six months (P < 0.01). The baseline MCHC
      increased from 313.6 +/- 2.7 milligrams to 324.3 +/- 4.29 milligrams (P < 0.05)
      during the third month of treatment. Hematocrit also increased significantly-from
      0.23 +/- 0.01 to 0.31 +/- 0.01 (P < 0.01) during the third and to 0.36 +/- 0.02
      (P < 0.001) during the sixth month of treatment. The erythrocyte counts from 2.73
      +/- 0.2 x 10(12)/l reached 3.69 +/- 0.24 x 10(12)/l (P < 0.01) at three months
      and 4.01 +/- 0.27 x 10(12)/l (P < 0.001) at six months. Reticulocyte counts
      increased from 1.93 +/- 0.37/1000 to 4.06 +/- 0.6/1000 after one month of
      treatment (P < 0.02) reaching the highest values during the second week of
      treatment. After the fourth week, reticulocyte number fluctuated slightly but not
      significantly above the baseline. The serum iron decreased from 12.0 +/- 0.36
      mumol/l to 10.5 +/- 1.0 mumol/l (P < 0.05) and 9.93 +/- 0.9 mumol/l (P < 0.02) at
      three and six months, respectively. The results revealed a non-significant
      reduction of serum ferritin and transferrin in the course of treatment. We also
      found a strong positive correlation between the dose of Eprex applied and the
      haemoglobin, hematocrit and the erythrocyte values in the treated patients.

PMID- 8566901
TI  - The most common cause of cascade stomach.
AB  - In a random sample of 396 patients with stomach complaints, 54 were found to have
      cascade stomach (overall frequency 13.6%). The analysis of the results showed the
      leading cause of this condition to be adhesion of the front costal diaphragm
      sinus.

PMID- 8566902
TI  - On combination treatment of hemangiomas in childhood.
AB  - We present 18 children with torso hemangiomas of predominant facial location in
      whom a combination treatment was used because of the rapid infiltrative growth,
      critical location and extent of the hemangiomas. The combinations of treatments
      used were: surgery plus sclerotherapy in three of the children; surgery plus
      corticosteroids--in three children; surgery plus cryotherapy in one; surgery,
      hormonal treatment and cryotherapy in one child; cryotherapy plus sclerotherapy
      in five children; cryotherapy plus hormonal treatment in two, beta-therapy and
      cryotherapy in three children. We assess the results of the treatments and
      discuss in details the combined treatment of giant hemangiomas in five children.

PMID- 8566903
TI  - Analysis of three methods of surgical intervention in the management of traumatic
      intracranial hematomas.
AB  - In the present study we discuss the methods of surgical intervention that are
      used in the management of traumatic intracranial hematomas in different periods
      after the craniocerebral trauma and the likelihood of hematoma recurrence after
      surgery. A total of 550 cases were retrospectively analysed. These patients were
      operated on employing osteoplastic trephination with a trephine Dofin,
      osteoclastic trephination, and osteoplastic trephination of the skull using a
      bone flap with 4 or 5 burr holes. The study results revealed that the greatest
      number of recurrences developed in the acute period of the trauma after
      performance of osteoclastic skull trephination. Osteoplastic trephinations using
      a bone flap with 4 or 5 burr holes yielded the fewest recurrences. In the periods
      after the fourth day of the trauma, corresponding to hematomas with subacute and
      chronic course, there was no statistically significant differences in the results
      after application of any one of the three methods of surgical interventions. A
      modification of the osteoplastic trephination with 4 burr holes is proposed. This
      method gave the best results in the operated patients in the three periods after
      cerebrocranial trauma.

PMID- 8566904
TI  - Immunohistochemical study on pigmented nevi (preliminary communication).
AB  - The human ABH blood-group antigen expression of cytokeratin, S-100 protein, and
      the melanoma-associated antigen was studied in 12 cases of pigmented nevi. The
      biotin-streptavidin immunostaining system was applied. ABH antigens were found
      both in the endothelial cells and in the germinative epidermal layer. The flat
      overlaying epithelium, single melanocytes and melanoblasts were positive for
      cytokeratin. Some basilar cells and the giant multinucleate cells in the Spitz
      nevi stained for S-100 protein. The melanoma-associated antigen was visualized in
      the upper epidermal layers as well as in some melanocytes. The present article
      discusses the specificity of the antigens studied as well as some immunologic
      traits of potential malignant development of Spitz nevi.

PMID- 8566905
TI  - Therapeutic problems in fronto-orbital fractures.
AB  - Along with the neurosurgical difficulties, the management of fronto-orbital
      fractures poses problems of aesthetical nature, especially those that arise in
      restoring the trauma-deformed face to its original, or close to original,
      appearance. The cranioplasty using duracryl to deal with defects secondary to
      impression fractures affecting the frontal sinuses presents a serious therapeutic
      problem because of the risk of suppuration. We report 48 patients treated in the
      Department of Neurosurgery of the University of Medicine, Plovdiv between 1981
      and 1990. Particular attention was paid to impression fractures affecting the
      frontal sinus. In addition to the classic method of surgical management of such
      fractures, a modification of cranioplasty in the region of the frontal sinus is
      presented which help to avoid the risk of suppuration. The surgical management
      was performed in two stages separated by a period of 6 to 12 months from the
      initial treatment of the wound and fracture. Connective tissue covering forms in
      this period which isolates the frontal sinus opening to the skull defect. Utmost
      sparing of this connective tissue during cranioplasty with duracryl is a
      guarantee of successful treatment.

PMID- 8566906
TI  - Use of orthopantomography in forensic identification.
AB  - The authors present a case of identification of a severely burnt corpse belonging
      to an unknown person by means of antemortem orthopantomography performed with a
      diagnostic purpose during a treatment of the person. A short review is made of
      the literature concerning the scope and use of orthopantomography for the
      purposes of forensic identification. Some practical aspects of the postmortem
      orthopantomography of both maxillary are given.

PMID- 8566907
TI  - [Pulmonary and pulmonary-related reflexes mediated by serotonin receptors in the
      peripheral nervous system].
AB  - It is known that serotonin is widely distributed in the body; its receptors are
      located in various tissues and organs. It has been reported that serotonin
      receptors without apparent synaptic structure exist in the peripheral nervous
      system. These serotonin receptors might be the target of circulatory serotonin.
      In particular, serotonin has a potent depolarizing action on vagal afferent
      nerves. This stimulation causes various autonomic reflexes, so-called von Bezold
      Jarisch reflex, that consist of bradycardia, hypotension and apnea. The
      peripheral 5-HT3-receptor subtype seems to be responsible for the initiation of
      these reflexes. The physiological and pathophysiological significance of these
      serotonin-induced modulations have not, however, been established. The present
      study was designed to examine the effects of exogenous serotonin on the
      chemosensitive afferent nerves including carotid sinus nerves, cervical vagus
      nerve, and efferent motor nerves, such as phrenic nerves and pharyngeal nerves.
      Because little is known about the involvement of the serotonergic system in the
      pulmonary reflex and pulmonary-related reflexes (swallowing or vomiting), the
      distribution of the motor component of these nerves within the brain stem of the
      rat was also determined.

PMID- 8566908
TI  - [Mutagenesis study of pharmacological receptors: approach to their structure
      function relationships].
AB  - Recent cDNA cloning of pharmacological receptors revealed their primary
      structures, and the following functional studies with those cloned receptors
      enabled us to discover the existence of various receptor subtypes. Each receptor
      has three characteristics properties: 1) ligand binding, 2) effector coupling and
      3) desensitization. Delineation of precise domains of a receptors involved in
      these functions is now an important matter. The molecular mapping of receptors
      would give us not only a rationale for designing selective drugs, but also new
      insight about the genotype-phenotype relationships of a certain kinds of
      hereditary diseases caused by a mutation of receptor genes. A mutagenesis study
      is a powerful approach for elucidating the structure-function relationships of
      pharmacological receptors. In contrast to a peptide, a protein is impossible to
      engineer in vitro. However, modulation of a specific codon in a given cDNA could
      bring about a substitution of a corresponding amino acid in the protein expressed
      in vivo. In this article, the popular strategies for generating artificially
      mutated receptors are discussed. This review will focus on three types of mutant
      receptors: 1) point mutation, 2) chimeric and 3) truncated receptors. The
      annotated bibliographies will also come in handy when devising experimental
      protocols.

PMID- 8566909
TI  - [Beneficial effects of the combination of idebenone and manidipine 2HCl on
      neurological deficits and histological changes following cerebrovascular lesions
      in stroke-prone spontaneously hypertensive rats].
AB  - We investigated the effects of the combination of idebenone, an energy metabolism
      enhancer, and manidipine 2HCl, a dihydropyridine-derivative calcium antagonist,
      on neurological deficits and histological changes in the brain and kidneys of
      stroke-prone spontaneously hypertensive rats (SHRSP) with cerebrovascular lesions
      (stroke). The SHRSP were kept on a 1% NaCl solution as their drinking water to
      synchronize the onset of stroke. After the onset of stroke symptoms, the salt
      solution was replaced with tap water. On the day following the onset of stroke,
      idebenone (50 mg/kg), manidipine 2HCl (2 mg/kg) or a combination of idebenone (50
      mg/kg) and manidipine 2HCl (2 mg/kg) was administered orally once a day for 3
      weeks. In the combination group and manidipine 2HCl-treated group, the
      neurological deficits after the onset of stroke were ameliorated during the
      entire experimentalperiod. Especially, the combination significantly decreased
      the number of days with severe neurological deficits as compared to the control
      group. The combination and manidipine 2HCl significantly recovered the decrease
      in body weight and ameliorated the increase of brain weight, which was mainly
      caused by edema, significantly as compared to the control group. Manidipine 2HCl
      ameliorated the histological changes in the brain. In the combination group, the
      histological changes in both the brain and the kidneys were ameliorated. In
      conclusion, the combination of idebenone and manidipine 2HCl significantly
      ameliorated the neurological deficits and the histological changes in the brain
      and the kidney of SHRSP with stroke as compared to each individual treatment. We
      concluded that manidipine 2HCl enhances the therapeutic effect of idebenone in
      the treatment of cerebrovascular diseases.

PMID- 8566910
TI  - [Quantitative autoradiographic analysis of the binding of mosapramine to dopamine
      D3-receptors].
AB  - The affinity of mosapramine, an iminodibenzyl antipsychotic, to dopamine D3
      receptors in rat brain was investigated by quantitative autoradiography of [3H]-7
      OH-DPAT, a selective D3-ligand. Autoradiograms showed restricted distribution of
      [3H]7-OH-DPAT binding sites, with very high levels on the islands of Calleja
      (ICj), olfactory tubercle (Tu) and nucleus accumbens, while low but distinct
      labeling was observed in the molecular layer of lobule 10 of the cerebellum and
      caudate putamen (CPu). Binding of [3H]7-OH-DPAT completely disappeared when 1
      microM dopamine was added, and it was reduced by the addition of mosapramine in a
      concentration-dependent manner. The displacing effect of mosapramine was more
      potent than that of haloperidol or clozapine in the brain regions examined.
      Mosapramine showed more potent affinity to receptors in Tu and ICj than those in
      CPu. On the other hand, haloperidol and clozapine did not show such regional
      differences. These results suggest that the high affinity of mosapramine to D3
      receptors participates in, at least in part, the development of the clinical
      effects of mosapramine.

PMID- 8566911
TI  - [Effect of KW-4679, a novel antiallergic drug, on platelet-activating factor
      (PAF)-induced bronchoconstriction, airway hyperresponsiveness and pulmonary cell
      accumulation in guinea pigs].
AB  - We assessed the effects of KW-4679 on bronchoconstriction, airway
      hyperresponsiveness and infiltration of inflammatory cells into the
      bronchoalveolar lavage (BAL) fluid induced by platelet-activating factor (PAF) in
      guinea pigs. (1) KW-4679 (1, 10 mg/kg, p.o.) significantly inhibited PAF-induced
      bronchoconstriction in anesthetized, ventilated guinea pigs. Ketotifen (1, 10
      mg/kg, p.o.) also significantly inhibited that reaction. (2) Intravenous
      administration of PAF (600 ng/kg/hr) to ventilated anesthetized guinea pigs
      induced bronchial hyperresponsiveness to histamine or substance P. PAF-induced
      bronchial hyperresponsiveness was significantly attenuated by pretreatment with
      KW-4679 (3 mg/kg, i.v.). (3) Exposure of guinea pigs to an aerosol of PAF induced
      an increase in the numbers of total leukocytes, eosinophils, neutrophils and
      lymphocytes in BAL fluid at 24 hr. KW-4679 (10 mg/kg, p.o.) reduced the increase
      in eosinophils in BAL fluid. Ketotifen (10 mg/kg, p.o.) partially reduced the
      increase in eosinophils in BAL fluid. (4) KW-4679 did not inhibit PAF-induced
      rabbit platelet aggregation. These observations indicate that KW-4679 attenuates
      the PAF-induced pulmonary reactions in guinea pigs and that these actions may be
      beneficial for the treatment of allergic bronchial asthma.

PMID- 8566912
TI  - Study on electrocution death by low-voltage.
AB  - Seven cases of electrocution death by low voltage (< 80 V) were studied. Autopsy
      was carried out and the death scene was investigated. The conditions for low
      voltage electrocution death, the state of the victim at the time of
      electrocution, postmortem examination and the nature of the electricity is
      discussed. It was pointed out that low-voltage electrocution was related to the
      nature of electricity, individual characteristics and environment conditions.

PMID- 8566913
TI  - Postmortem degradation of administered ethanol-d6 and production of endogenous
      ethanol: experimental studies using rats and rabbits.
AB  - Deuterium-labeled ethanol-d6 was employed to study the metabolism and postmortem
      change of ethanol in putrefied organ tissues. First, 4 ml/kg body weight of 25%
      (w/v) solution of ethanol-d6 was administered orally to each of 15 rats. The
      heart blood and organs were collected 15-90 min after the administration and the
      ethanol-d6 was analyzed by head space gas chromatography/mass spectrometry. The
      ethanol-d6 concentration in the organ tissues reached its maximum at 15 min after
      the administration and then gradually declined, showing the same pattern as human
      ethanol metabolism. Ethanol-d6 (3 ml of the same solution/kg body weight) was
      injected into the vein of a rabbit's ear (total of 12 rabbits). The rabbit was
      killed with carbon monoxide 30 min after the administration and the carcass was
      allowed to stand for 1-4 days at 30 degrees C in a moist chamber. The
      concentration of ethanol-d6 decreased moderately. Postmortem ethanol and 1
      propanol concentrations, in contrast, showed marked increases 2.5 days and more
      after sacrifice in line with the degree of putrefaction of each organ tissue
      including skeletal muscle. This suggests the postmortem activation of micro
      organism activity. These results indicate that ethanol concentrations in cadaver
      tissues must be carefully assessed with due consideration of postmortem
      degradation and production.

PMID- 8566914
TI  - Diagnostic ability of D-dimer in the establishment of the vitality of wounds.
AB  - The potential of skin measurements of D-dimer (DD), a specific derivative of
      crosslinked fibrin, for the diagnosis of the vital origin of wounds was
      investigated in 67 human vital skin wounds and homolateral control pieces of skin
      from 53 autopsies performed at the Institute of Legal Medicine of Coimbra
      (Portugal) during 1992. Our results demonstrate that DD levels for the incised
      vital skin wounds (n = 50) were much higher on average than their controls (P <
      0.01) which were actually incised injuries produced postmortem at the autopsy. We
      did not find any statistical difference in average DD levels among the remaining
      injuries (seven abrasions and ten contusions) in comparison to their respective
      controls. DD may be used, with certain limitations, as a marker of the vitality
      of incised wounds. The authors believe this is the first time this marker has
      been applied in forensic pathology. It is an example of an easy and quick
      application technique, with the added advantage of low cost.

PMID- 8566915
TI  - alpha-Phenylethylamine identified in judicial samples.

PMID- 8566916
TI  - Postmortem electrical excitability of skeletal muscle: preliminary investigation
      of an animal model.
AB  - Presented is a preliminary study of the feasibility of using an animal model to
      investigate the postmortem time-dependent decay in muscular response, when
      subjected to electrical stimulation and to develop an animal model for the
      assessment of the use of electrical excitability as a method for determining the
      postmortem period of a human corpse. Analysis of the results shows a correlation
      between the rate of decay of muscular response with the postmortem interval.

PMID- 8566917
TI  - Investigation of the impurities found in methamphetamine synthesised from
      pseudoephedrine by reduction with hydriodic acid and red phosphorus.
AB  - The synthesis of methamphetamine from pseudoephedrine via the reduction with
      hydriodic acid and red phosphorus was studied and the impurities which were
      generated, along with the methamphetamine, were investigated. Some of the
      impurities found have been reported previously, while the diastereoisomers of N
      methyl-N-(alpha- methylphenethyl)amino-1-phenyl-2-propanone and the cis-cinnamoyl
      derivative of methamphetamine are reported here for the first time. Further work
      on the sequence of reactions occurring in this reduction is also reported.

PMID- 8566918
TI  - Tetrachloroethylene fatality: case report and simple gas chromatographic
      determination in blood and tissues.
AB  - We have described a simple, precise and sensitive assay of tetrachloroethylene in
      whole blood and tissues, suitable both for emergency cases and forensic medicine.
      The method employs gas chromatography and electron capture detection. The case
      report concerns a fatal exposure of a child to tetrachloroethylene.
      Concentrations of the chemical in different fluids and tissues were determined
      and compared to two other previously published fatalities.

PMID- 8566919
TI  - Detection of amphetamines in urine using head space-solid phase microextraction
      and chemical ionization selected ion monitoring.
AB  - An accurate, simple and rapid method for qualitative and quantitative analysis of
      amphetamine and methamphetamine in urine was developed using head space-solid
      phase microextraction and gas chromatography-mass spectrometry/chemical
      ionization selected iron monitoring. A vial containing a urine sample potassium
      carbonate and pentadeuterated methamphetamine which was used as an internal
      standard was heated at 80 degrees C for 20 min. The needle of a solid phase
      microextraction device was passed through the septum, and the extraction fiber in
      the needle was exposed for 5 min in the head space of the vial. The needle was
      removed from the vial and inserted into the injection port of gas chromatograph
      or gas chromatograph/mass spectrometer. The compounds adsorbed on the fiber were
      detached by exposing the fiber in the injection port, and analyzed. The proposed
      method was more than 20 times more sensitive than the conventional head space
      method.

PMID- 8566920
TI  - Experimental studies on postmortem diffusion of ethanol-d6 using rats.
AB  - In an investigation of postmortem ethanol diffusion deuterium-labeled ethanol-d6
      was instilled by peroral gavage immediately after death by CO into the stomach of
      rat carcasses which were subsequently kept for 12-72 h at 5 or 30 degrees C. The
      heart blood, abdominal fluid and several tissues were collected and analyzed by
      head space gas chromatography-mass spectrometry. Rat carcasses showed no
      macroscopic changes until at least 72 h at 5 degrees C, and 12 h at 30 degrees C.
      At 30 degrees C, slight macroscopic change was observed after 24 h, moderate
      change after 48 h and marked change after 72 h. In the abdomen ethanol-d6
      diffused gradually into neighboring organs (hepatic left lobe, left kidney and
      spleen) at 5 degrees C, with ethanol-d6 reaching a peak concentration of 0.75
      2.38 mg/g at 24 h. At 30 degrees C, ethanol-d6 was also detected in neighboring
      organs and reached a peak concentration of 1.06-2.61 mg/g at 12 h. Thereafter,
      the ethanol-d6 concentration in the liver, kidney and spleen decreased, with
      concentrations ranging from 0.30 to 0.61 mg/g at 30 degrees C and 0.05 to 1.47
      mg/g at 5 degrees C at 48 h. In the femoral skeletal muscle, ethanol-d6 was not
      detected until 24 h or more storage at 30 degrees C and never detected at 5
      degrees C. In the brain and the organs in the thoracic cavity ethanol-d6 was
      detected after 12 h or more at 5 or 30 degrees C. Comparison of these results of
      direct peroral gastric instillation with those when ethanol-d6 was injected into
      the stomach through a laparotomy incision suggest that the brain and thoracic
      cavity changes were a result of diffusion from the mouth and esophagus. After 24
      h at 30 degrees C, the postmortem ethanol production (0.33-0.85 mg/g) was
      comparable to those in previous reports. These results indicate that the
      assessment of ethanol concentration in the heart blood and organs in autopsy
      cases must be carefully conducted in comparison with the alcohol content of the
      stomach.

PMID- 8566921
TI  - Effects of cocaine administration route on the formation of cocaethylene in
      drinkers: an experiment using rats.
AB  - The effects of cocaine administration route on the formation of cocaethylene, an
      active metabolite of cocaine produced in the presence of ethanol, were
      investigated using rats. When 20 mg/kg cocaine was administered into the stomach
      together with 2 g/kg ethanol, maximum liver concentrations of cocaine and
      cocaethylene, 8410 +/- 3600 and 1680 +/- 520 ng/g, respectively, were observed at
      15 min. In other tissues the maximum levels of both the substances were attained
      in 30 min, but were much lower than those in the liver. Intramuscular
      administration of 20 mg/kg cocaine with 2 g/kg oral ethanol gave levels of liver
      cocaine as low as 103 +/- 29 to 150 +/- 35 ng/g, resulting in no detection of
      liver cocaethylene over the entire 180-min study period, although gradual
      accumulation of cocaethylene was observed in other tissues. The accumulation
      patterns of cocaine and cocaethylene in blood of alcohol-intoxicated rats after
      the i.m. administration of cocaine were similar to those in blood of drinkers
      after nasal insufflation of cocaine. Despite i.v. administration of 1 mg/kg
      cocaine with 2 g/kg oral ethanol, no detectable amounts of cocaethylene appeared
      in any tissues over the entire 60-min study period. The present findings are
      considered to be of importance in the fields of forensic and clinical toxicology
      for clarifying (1) the rate of in vivo cocaethylene formation and (2) the
      distribution of cocaine and cocaethylene in blood and tissues.

PMID- 8566922
TI  - Determination of manganese in human brain samples.
AB  - A method is presented for the determination of manganese (Mn) in human tissue
      samples (especially brain) by graphite furnace atomic absorption spectrophometry
      (GFAAS). After complete digestion by a mixture of concentrated nitric acid
      (HNO3)/concentrated perchloric acid (HClO4) (50:50, v/v), the samples are assayed
      on a Perkin-Elmer 5100 PC apparatus, equipped with transversal graphite tubes and
      a Mn-specific hollow cathode lamp. The furnace conditions are as follows (for
      each step: temperature (degree C)/ramp (s)/duration (s)) dry 120/1/40; char
      1200/5/10; atomization 2250/0/4; pyrolysis 2400/1/1. Zeeman correction is
      employed. The method is linear over the range 0.05 to 5.00 micrograms/g wet
      tissue, and the limit of detection for Mn is about 0.01 microgram/g wet tissue.
      This simple and rapid method may be of value for the post-mortem assessment of Mn
      accumulation in brain structures due to occupational or iatrogenic exposure. An
      application is presented in which elevated levels of Mn were determined in the
      brain samples of a 63-year-old female deceased after long-term total parenteral
      nutrition involving Mn supplementation.

PMID- 8566923
TI  - A fatal dothiepin overdose.
AB  - High pressure liquid chromatography coupled to photodiode array detector and
      capillary gas chromatography coupled to mass spectrometry were employed to
      quantify dothiepin in biological fluids, tissues and hair in a death attributed
      to oral dothiepin (Prothiaden) ingestion. The blood concentration of dothiepin
      was 5.75 mg/l. Hair analysis clearly indicated a chronic antidepressant exposure,
      with a dothiepin concentration of 1.89 ng/mg hair. Results are discussed in the
      light of the existing literature.

PMID- 8566924
TI  - Intracranial injuries by a screwdriver.
AB  - Two patients with unusual intracranial foreign bodies are presented. Intracranial
      injuries produced by a piece of screwdriver as a wounding agent have not yet been
      reported in the literature. In one of our two cases we had to deal with homicide
      and in another with accidental self-inflicted injury. Both patients died, 5 and
      14 days, respectively, after successful removal of the foreign body. In both
      cases death was due to brain ischaemia and the resulting oedema secondary to
      arterial injury.

PMID- 8566925
TI  - Urinary catecholamines as markers of hypothermia.
AB  - Although raised urinary CA levels provide good supportive evidence of prolonged
      agonal stress in hypothermic deaths, the CA index is not, in our experience, of
      particular diagnostic significance.

PMID- 8566926
TI  - [Reality of drug poisoning and screening tests].

PMID- 8566927
TI  - [General characteristic and toxicity of VX].

PMID- 8566928
TI  - Etiology and prognosis of liver cirrhosis in elderly patients.
AB  - We compared the etiology and prognosis of liver cirrhosis in patients age 60 and
      older with that of patients under age 60 during the 1980s (1981-89, n = 207). Non
      A, non-B hepatitis (NANB) was significantly more prevalent in the elderly (p <
      0.05), and the mean age of NANB and alcoholic cirrhosis (Alc) were significantly
      older than those with hepatitis B virus (HBV) (p < 0.05). Evaluation using
      hepatitis C virus (HCV) antibody also revealed significantly higher mean age of
      HCV (p < 0.05). Male patient was predominant in the younger patients than in the
      elderly patients. (M/F = 2.94 and 1.33, respectively) The estimated 5-year
      survival rate was 73.1% in the younger patients and 60.2% in the elderly patients
      (p < 0.05). Multivariate analysis revealed that male sex, a lower serum albumin
      level, and the presence of the encephalopathy were significantly associated with
      poor prognosis in the elderly, while a lower serum cholinesterase level and a
      higher indocyanin green retention rate at 15 minutes (ICGR15) were significantly
      associated with poor prognosis in younger patients. However, causes of deaths
      were not significantly different between the younger patients and the elderly
      patients, the proportion of deaths unrelated to liver disease predominated in the
      elderly patients. Thus, the etiology and the prognostic factors of liver
      cirrhosis in elderly patients differ from those in younger patients.

PMID- 8566929
TI  - [Steroid-responsive sensorineural hearing loss with low tone loss].
AB  - Five cases of sensorineural hearing loss of sudden onset were reviewed. They were
      not responsive to administration of ATP and Vit. B12, but very responsive to
      steroid administration. All the patients were male and showed hearing loss in low
      frequencies in pure tone audiogram. Administration of steroid recovered hearing
      impairment immediately. However, cessation of steroid aggravated the recovered
      hearing. Serological and immunological examinations did not show any abnormal
      findings on all the patients. It was considered that these five patients had
      characteristics of both steroid-sensitive and low tone-loss type sensorineural
      hearing losses.

PMID- 8566930
TI  - Nitric oxide and the control of renin secretion.
AB  - Research during recent years has established nitric oxide as a unique signaling
      molecule that plays important roles in the regulation of the cardiovascular,
      nervous, renal, immune and other systems. Nitric oxide has also been implicated
      in the control of the secretion of hormones by the pancreas, hypothalamus,
      pituitary and other endocrine glands, and evidence is accumulating that it
      contributes to the regulation of the secretion of renin by the kidneys. The
      enzyme nitric oxide synthetase is present in vascular and tubular elements of the
      kidney, particularly in cells of the macula densa, a structure that plays an
      important role in the control of renin secretion. Guanylyl cyclase, a major
      target for nitric oxide, is also present in the kidney and is responsive to
      changes in nitric oxide levels. Drugs that inhibit nitric oxide synthesis
      generally suppress renin release in vivo and in vitro, suggesting a stimulatory
      role for the L-arginine-nitric oxide pathway in the control of renin secretion.
      Under some conditions, however, blockade of nitric oxide synthesis increases
      renin secretion. Recent studies indicate that nitric oxide not only contributes
      to the regulation of basal renin secretion, but also participates in the renin
      secretory responses to activation of the renal baroreceptor, macula densa and
      beta adrenoceptor mechanisms that regulate renin secretion. Future research
      should clarify the mechanisms by which nitric oxide regulates the secretion of
      renin and establish the physiological significance of this regulation.

PMID- 8566931
TI  - Differential activation of beta 1-, beta 2- and beta 3-adrenoceptors by
      catecholamines in white and brown adipocytes.
AB  - This review summarizes the experiments performed by various groups to determine
      how the activation of the different beta-adrenoceptors (beta-ARs) is ordinated
      when they are present in the same fat cell and involved in the same biological
      event. When expressed after the transfection of their genes in Chinese hamster
      ovary cell (CHO cells), beta 1- and beta 2-ARs present a higher affinity for
      catecholamines than beta 3-ARs. In vitro, the lipolytic effect induced by low
      concentrations of catecholamines in dog and rat white fat cells is due to the
      selective activation of beta 1- and/or beta 2-ARs. Higher concentrations only are
      able to activate beta 3-ARs. Similar results have been obtained in rat brown
      adipocytes. On the other hand, the lipolytic effect of catecholamines in human
      and primate adipocytes does not involve a beta 3-AR component whatever the
      concentration used. In vivo experiments in the dog have also shown that
      lipomobilization induced by low doses of isoprenaline only involved beta 1- and
      beta 2-AR activation, this effect being blocked by beta 1-/beta 2-antagonist
      pretreatment. However, in the same blockade conditions, perfusion of a 10-fold
      higher dose of isoprenaline revealed a beta 3-AR contribution in the
      lipomobilizing effect. These data showed that brown and white adipocyte beta 3
      ARs possess a lower affinity for catecholamines than beta 1- and beta 2-ARs and
      are only recruited by high concentrations of the amines.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8566932
TI  - Beta 3-adrenoceptors and intestinal motility.
AB  - Early substantial evidence of the low susceptibility to beta-adrenoceptor
      antagonists of non alpha-adrenergic responses reducing gut motility and tone was
      reluctantly accepted as indicating a third beta-receptor subtype different from
      the beta 1 and beta 2. This applied likewise to lipolysis until new selective
      "lipolytic" beta-agonists poorly effective at established beta-receptors were
      introduced. Shortly afterwards these "lipolytic" as well as certain newer and
      even more selective beta-adrenoceptor agonists were shown to be potent inhibitors
      of intestinal motility. The latter are the "gut-specific"
      phenylethanolaminotetralins whose availability as pure isomers attested to the
      stringent stereochemical requirements for selectivity at non-beta 1, non-beta 2
      beta-adrenoceptors. Acceptance of the functionally based concept of a beta 3
      adrenoceptor was boosted on structural grounds by molecular biology studies.
      Sequence analysis indicated the existence in humans and rodents of genes coding
      for a third subtype of beta-receptor that, when expressed in transfected
      heterologous cells, had a pharmacological profile distinct from the previously
      established subtypes. Finally, aryloxypropanolaminotetralins have been prepared
      as the first selective antagonists of beta 3-adrenoceptors, thus providing
      unambiguous conclusive evidence of the distinctive functional features of those
      abundant in the rat colon. The therapeutic potential in gastroenterology of the
      newer compounds targetable on the beta 3-adrenoceptor is suggested by their
      potent intestinal action in vivo in animal models without any of the
      cardiovascular or other unwanted effects of conventional beta-adrenoceptor
      agonists and antagonists, and by the clinically confirmed importance of beta
      adrenergic control of motor function throughout the alimentary canal. However,
      open questions include the incidence of species-related differences in beta 3
      adrenoceptors, and as yet there are no data on gastrointestinal functions in
      humans under the influence of drugs designed to act selectively at these
      receptors.

PMID- 8566933
TI  - How sympathetic tone maintains or alters arterial pressure.
AB  - After chronic sympathectomy or sinoaortic denervation (SAD), arterial pressure
      (AP) becomes extremely unstable, especially because of movement-related depressor
      episodes. The simultaneous measurement of AP and regional blood flows in
      sympathectomized and SAD rats indicates that these depressor episodes are
      accompanied by strong regional vasodilations, possibly involving an
      autoregulatory component. The sympathetic nervous system, mainly through
      baroreflex modulation of its activity, overrides these responses and thereby,
      considerably limits the AP variability. In the conscious unrestrained rat, AP
      fluctuates in a narrow range (variation coefficients calculated over 1-hour beat
      to-beat recordings are typically approximately 5%). This variability of AP
      involves sympathetically-mediated pressor episodes that are coupled to behavior
      and alerting environmental stimuli. Regarding the latter, studies in SAD rats
      point to an opposing interaction between centrally-induced sympathoexcitation and
      baroreflex activation. Another component of normal AP variability appears as an
      oscillation centered around 0.4 Hz. Spectral analysis of AP and regional
      hemodynamic variables indicates that this oscillation is secondary to rhythmic
      fluctuations in the vasomotor sympathetic tone that are synchronized by the
      arterial baroreceptor reflex. It is concluded that both stability and normal
      variability of AP critically depend on the baroreflex control of the sympathetic
      vascular tone.

PMID- 8566934
TI  - Role of PAF in the late airway microvascular leakage induced by antigen in IgE
      sensitized rat.
AB  - The effect of the antagonist of platelet-activating factor (PAF), BN 50730, on
      PAF-and antigen- induced increase in microvascular leakage, using Evans blue dye
      as an index of permeability, was investigated in rat pulmonary tissues. PAF (1
      microgram/kg, iv) induced a marked increase in Evans blue dye content in trachea,
      main bronchi and small bronchi, that was significantly reduced upon pretreatment
      of the rats with BN 50730 (25 mg/kg, orally) and by the serotonin antagonist,
      methysergide (1 mg/kg, iv), only in the small bronchi. Serotonin also induced an
      increase in microvascular leakage in the three tissues that was significantly
      inhibited when the animals were treated with methysergide but not by BN 50730. In
      contrast, histamine and lyso-PAF did not induce significant increase in Evans
      blue dye content. Intravenous injection of antigen to IgE-sensitized rats induced
      a biphasic increase in vascular permeability. An early increase in vascular
      permeability in trachea, main bronchi and small bronchi was observed 10 minutes
      after the injection of the antigen, and this phenomenon was significantly reduced
      upon treatment of the rats with methysergide, whereas, BN 50730 was ineffective.
      A late increase in vascular permeability was noted in the three tissues, with a
      maximum at 120 minutes and representing 30-40% of the magnitude of the first
      phase. Administration of BN 50730 (25 mg/kg) to the animals, evoked a significant
      inhibition of this increase in microvascular leakage, whereas, methysergide only
      significantly reduced the one induced by antigen in the trachea.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8566935
TI  - Evaluation of antiproliferative effects of the somatostatin analogue somatuline
      in a rabbit model of traction retinal detachment.
AB  - As growth hormone (GH) and insulin-like growth factor type I (IGF-I) have been
      suggested to be involved in the development of some proliferative ocular
      disorders, we investigated the eventual antiproliferative properties of a long
      acting somatostatin analogue, somatuline or BIM23014 (IPSEN Biotech, France), in
      an original model of experimental proliferative vitreoretinopathy. Two studies
      were separately done to investigate respective effects of subcutaneously- and
      intravitreally administered somatuline. Injections of 10(7) human platelets
      freshly prepared from a unique normal donor were injected into the vitreous,
      cavity of pigmented rabbits. The first experiment consisted of evaluating
      vitreoretinal proliferation in 17 eyes from rabbits receiving subcutaneous
      injections of 25 micrograms/kg of BIM23014, given twice a day, from the day after
      injection for one month. A group of 14 eyes served as non treated controls. The
      second experiment was conducted in 33 eyes: 10 received intravitreally 1
      microgram of somatuline given once a week for one month, 10 eyes similarly
      received 5 micrograms/week of somatuline, the remaining 13 eyes serving as
      controls with intravitreal injections of sterile saline. All animals were
      examined ophthalmoscopically twice a week for one month in a masked manner, and
      sacrificed at the end of the experiment for histological and immunohistological
      analyses. In all but two eyes from the subcutaneously treated group, intravitreal
      and preretinal membranes formed, five to eight days after platelet injection.
      Intravitreal proliferation progressively increased, resulting in various degrees
      of vitreoretinal retraction and retinal detachment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8566936
TI  - Cardiovascular variability after rilmenidine challenge: assessment of acute
      dosing effects by means of spectral analysis.
AB  - Short-term fluctuations in blood pressure (BP) and heart rate (HR) were analysed
      in a group of twelve subjects with mild hypertension. Indirect finger BP was
      measured by a Finapres device. The effects of an oral dose of rilmenidine (1 mg)
      were studied in a double-blind cross-over placebo-controlled study. Compared with
      placebo, rilmenidine reduced the variability of standing BP after 2 hours as
      estimated from the standard deviation of systolic BP which diminished by 20%.
      Spectral analysis of fluctuations in BP showed this reduction predominated in the
      mid frequency (MF) region corresponding to 10-second period oscillations, which
      depend on the activity of the autonomic nervous system. The average reduction in
      MF component for standing systolic BP was 24%. In addition the MF component for
      HR was reduced by 17%. This frequency domain analysis demonstrates a modified BP
      and HR variability profile with an acute dosing of rilmenidine. This effect being
      limited to the MF fluctuations in standing position orients towards an effect of
      the drug on the sympathetic cardiovascular control.

PMID- 8566937
TI  - Characterization of lymphocyte beta-adrenoceptor activity and Gs-protein in
      patients with rheumatic heart valvular disease.
AB  - In order to test whether the beta-adrenoceptor activity in rheumatic heart
      valvular disease depends on the ventricular load conditions, we determined their
      density and binding affinity to [125I]-iodocyanopindolol in lymphocytes, as well
      as plasma catecholamine and cAMP levels in 69 patients with regurgitant and
      stenotic lesions of the aortic and mitral valves. The patients were classified as
      having left ventricular pressure overload (LVP), left ventricular volume overload
      (LVV), mixed lesions (MOL) or right ventricular pressure overload (RVP). The beta
      adrenoceptor activity was determined by radioligand binding methods,
      catecholamines by high performance liquid chromatography using an electrochemical
      detector and cAMP by radioimmunoassay. The mean beta-adrenoceptor density (Bmax)
      of the control group was 60.1 +/- 9.5 fmol (n = 29) per 10(6) lymphocytes. In the
      study population, the density was decreased by 83% in LVP, 78% in LVV, 87% in MOL
      and 86% in RVP. Plasma norepinephrine was elevated by 89% in LVP and 60% in MOL,
      epinephrine by 43% in LVP, 50% in VOL, 115% in MOL and 20% in RVP, while dopamine
      was not significantly changed, and cAMP was slightly elevated in all four groups.
      Screening for activating mutational changes in the Gs alpha-protein gave negative
      results, possibly dissociating the elevation in plasma cAMP from stimulatory
      effects of such abnormalities in the Gs-protein signaling.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8566938
TI  - Facilitating clinical research in the 1990s and beyond: challenges facing
      clinical trial registers.

PMID- 8566939
TI  - How good are volunteers at searching for published randomized controlled trials?
      The OSTR Collaborative Group. Ottawa Stroke Trials Registry.
AB  - The Ottawa Stroke Trials Registry (OSTR) collects information on all randomized
      controlled trials (RCTs), in all languages, in which the primary focus is stroke.
      Published trials are added to the registry database once they have been
      identified by volunteers hand searching journals. We undertook this study to
      assess volunteer sensitivity, specificity, positive and negative predictive
      values, accuracy and reliability in identifying RCTs. Three volunteers
      participated in this study. The complete contents of five years of one journal
      were searched (n = 240) as were ten research reports from five journals.
      Volunteer sensitivity, specificity, positive and negative predictive values, and
      accuracy was 89.5%, 100%, 100%, 99.1%, and 99% respectively. Inter volunteer
      reliability was 0.87. Searching the published literature to identify RCTs is an
      enormous task. These results indicate that volunteers, with minimal training, can
      effectively contribute to this endeavour.

PMID- 8566940
TI  - A meta-analysis of randomized, double-blind, placebo-controlled studies of the
      effect of buflomedil on intermittent claudication.
AB  - A meta-analysis was performed on the results of clinical trials of buflomedil in
      intermittent claudication. The analysis used results from 744 patients enrolled
      in ten studies, conducted at 42 centers in seven countries. All studies were
      randomized, double-blind, placebo-controlled trials which measured improvement in
      "pain-free" walking distance by treadmill ergometry as the primary measure of
      efficacy. The meta-analysis results were based on "effect size", a standardized
      difference in mean response between buflomedil and placebo. Results demonstrated
      a statistically superior response to buflomedil compared with placebo, indicating
      that the average buflomedil treated patient was likely to have a greater
      improvement in walking distance than at least 60% of the placebo treated
      patients. Results were corroborated using various weighting schemes proportional
      to study quality ratings and sample sizes.

PMID- 8566941
TI  - Programs, databases, and expert systems for human geneticists--a survey.
AB  - We present an overview of the variety of databases and programs that offer
      substantial aid to medical and molecular geneticists. Databases and expert
      systems for genetic diseases and birth defects, programs for segregation and
      linkage analysis, certain DNA and protein sequence databases, and information
      resources in general for molecular biology are addressed. These systems cannot be
      used effectively without the newly developed techniques of information exchange
      based on international computer networks. A short introduction is given to the
      Internet and to European institutions and organizations that offer help with the
      acquisition and use of bioinformatic resources.

PMID- 8566942
TI  - Familial non-syndromic conotruncal defects are not associated with a 22q11
      microdeletion.
AB  - Molecular studies have shown microdeletions in region q11 of chromosome 22 in
      nearly all patients with DiGeorge, velocardiofacial and conotruncal anomaly face
      syndromes (DGS, VCFS and CTAFS, respectively) and in a high percentage of non
      syndromic familial cases of conotruncal defects (CTD). CTD account for roughly a
      fourth to a third of all non-syndromic congenital heart defects (CHD), thus,
      22q11 could harbor a major genetic factor of CHD. We searched for a 22q11
      microdeletion in familial cases of non-syndromic CTD. Thirty-six cases of various
      isolated CTD, that is without history of hypocalcemia, immune deficiency, absent
      thymus, and dysmorphic appearance, were selected. With 48F8, a cosmid probe
      localized in the smallest deleted region of the DiGeorge critical region (DGCR),
      we found no deletions by fluorescence in situ hybridization in these 36 affected
      individuals of 16 families with recurrent CTD. Moreover, D22S264, a
      microsatellite localized at the distal part of the largest deleted region, was
      used to genotype the patients. Thirty-two patients out of 37 were heterozygous
      and hence not deleted at this locus, whereas 5 were uninformative. In conclusion,
      there are no large deletions in familial cases of various CTD, whether these
      defects are identical or not within a family. This result does not rule out other
      minor anomalies in this chromosomal region.

PMID- 8566943
TI  - Association of CTG repeats and the 1-kb Alu insertion/deletion polymorphism at
      the myotonin protein kinase gene in the Japanese population suggests a common
      Eurasian origin of the myotonic dystrophy mutation.
AB  - We have studied linkage disequilibrium between CTG repeats and an Alu
      insertion/deletion polymorphism at the myotonin protein kinase gene (DMPK) in 102
      Japanese families, of which 93 were affected with myotonic dystrophy (DM). All of
      the affected chromosomes are in complete linkage disequilibrium with the Alu
      insertion allele. Among the normal chromosomes, alleles of CTG repeats 5 and > or
      = 17 are exclusively associated with the insertion allele. On the other hand,
      intermediate alleles of 11-16 repeats show a significantly greater association
      with the deletion allele. A strikingly similar pattern of linkage disequilibrium
      observed in European populations suggests a common origin of the DM mutation in
      the Japanese and European populations.

PMID- 8566944
TI  - Arylsulfatase A pseudodeficiency in Chinese.
AB  - Arylsulfatase A (ASA) pseudodeficiency was found to be much rarer in Taiwan than
      in most western countries (2.5% versus 7.3%-20% carrier rate). The linkage of two
      mutations (A2725G and A1788G) in the pseudodeficiency allele was preserved in
      Chinese, and A2725G did not occur alone. This unusual linkage of mutations has
      not been fully explained previously because the frequency of A2725G alone was not
      clear (as low as 4% in the only report). However, A1788G was found in 55 of 160
      (34.4%) DNA samples tested in this study. These data suggest that the A2725G
      mutation occurred in DNA that already contained the A1788G change, at an ancient
      time in one of our common ancestors.

PMID- 8566945
TI  - Non-invasive early prenatal molecular diagnosis using retrieved transcervical
      trophoblast cells.
AB  - Fetal DNA was recovered from 17 of 39 (44%) transcervical cell (TCC) samples
      obtained between 7 and 9 weeks of gestation by endocervical canal flushing.
      Trophoblast retrieval was adequate for polymerase chain reaction (PCR)
      amplification of Y chromosome-specific DNA sequences and detection of paternal
      specific microsatellite alleles. The fetal sex predicted by PCR in TCCs was
      confirmed in all cases by karyotype analysis of chorionic villi at 10 weeks of
      gestation. The absence of the disease-associated paternal alleles in TCC samples
      from two pregnancies at risk for spinal muscular atrophy and myotonic dystrophy
      predicted unaffected fetuses in agreement with subsequent results on chorionic
      villi and newborns' leukocytes. A trisomy 21 fetus was diagnosed in TCCs using
      fluorescent in situ hybridization (FISH) and semi-quantitative PCR analysis of
      superoxide dismutase-1 (SOD 1). Present experience indicates that TCC sampling is
      a promising technique for early prenatal monitoring of Mendelian disorders and
      chromosome aneuploidy.

PMID- 8566946
TI  - Sex difference in the regulation of plasma high density lipoprotein cholesterol
      by genetic and environmental factors.
AB  - Association between high density lipoprotein (HDL) cholesterol concentration and
      restriction fragment length polymorphisms at the cholesteryl ester transfer
      protein (CETP) gene locus was studied in a random population-based cohort of 526
      Caucasian subjects (259 men, mean age 50.9 years, and 267 women, mean age 51.8
      years). HDL cholesterol concentration was adjusted for age, body mass index,
      alcohol consumption, smoking and plasma triglyceride and low density lipoprotein
      cholesterol levels. In females, the HDL cholesterol levels were associated with
      TaqIB polymorphism (1.46 mmol/l in the B1B1 genotype, 1.56 mmol/l in B1B2 and
      1.72 mmol/l in B2B2, P = 0.0001 for the trend). In contrast, this was not
      observed in men (1.24, 1.20, 1.27 mmol/l, NS). The association was seen even in
      women who were current smokers (1.41, 1.56, 1.75 mmol/l, n = 72, P = 0.007), but
      not in male smokers (1.26, 1.19, 1.14 mmol/l, n = 102, NS). In male non-smokers
      the association was weak (1.22, 1.20, 1.32 mmol/l, n = 157, P = 0.05). In
      postmenopausal women not receiving hormone replacement therapy (n = 108), the
      association continued to be present, although weaker (1.50, 1.58, 1.70 mmol/l, P
      = 0.06). CETP activity (n = 101) tended to be lower in subjects with the B2B2
      genotype. In conclusion, a clear-cut sex difference was observed in the genotype
      effect on plasma HDL cholesterol levels. The slight attenuation of the gene
      dosage effect after menopause suggests that the gender difference may be, at
      least in part, due to sex hormones. A genetic subgroup (men with the B2B2
      genotype) particularly susceptible to the HDL cholesterol decreasing effect of
      smoking could be demonstrated.

PMID- 8566948
TI  - Increased incidence of hyperhaploid 24,XY spermatozoa detected by three-colour
      FISH in a 46,XY/47,XXY male.
AB  - Meiotic segregation of gonosomes from a 46,XY/47,XXY male was analysed by a three
      colour fluorescence in situ hybridisation (FISH) procedure. This method allows
      the identification of hyperhaploid spermatozoa (with 24 chromosomes), diploid
      spermatozoa (with 46 chromosomes) and their meiotic origin (meiosis I or II).
      Alpha satellite DNA probes specific for chromosomes X, Y and 1 were observed on
      27,097 sperm nuclei. The proportions of X- and Y-bearing sperm were estimated to
      52.78% and 43.88%, respectively. Disomy (24,XX, 24,YY, 24,X or Y,+1) and diploidy
      (46,XX, 46,YY, 46,XY) frequencies were close to those obtained from control
      sperm, whereas the frequency of hyperhaploid 24,XY spermatozoa (2.09%) was
      significantly increased compared with controls (0.36%). These results support the
      hypothesis that a few 47,XXY germ cells would be able to complete meiosis and to
      produce mature spermatozoa.

PMID- 8566947
TI  - A common region of loss of heterozygosity in Wilms' tumor and embryonal
      rhabdomyosarcoma distal to the D11S988 locus on chromosome 11p15.5.
AB  - The development of Wilms' tumor has been associated with two genetic loci on
      chromosome 11: WT1 in 11p13 and WT2 in 11p15.5. Here, we have used loss of
      heterozygosity (LOH) in Wilms' tumors to narrow the WT2 locus distal to the
      D11S988 locus. A similar region was apparent for the clinically associated tumor,
      embryonal rhabdomyosarcoma. We have also demonstrated that a constitutional
      chromosome translocation breakpoint associated with Beckwith-Wiedemann syndrome
      and an acquired somatic chromosome translocation breakpoint in a rhabdoid tumor
      each occur in the same chromosomal interval as the smallest region of LOH in
      Wilms' tumors and embryonal rhabdomyosarcoma. Finally, we report the first Wilms'
      tumor without a cytogenetic deletion that shows targeted LOH for 11p15 and 11p13
      while maintaining germline status for 11p14.

PMID- 8566949
TI  - Cockayne syndrome complementation group B associated with xeroderma pigmentosum
      phenotype.
AB  - Two siblings have been reported whose clinical manifestations (cutaneous
      photosensitivity and central nervous system dysfunction) are strongly reminiscent
      of the DeSanctis-Cacchione syndrome (DCS) variant of xeroderma pigmentosum (XP),
      a severe form of XP. Fibroblasts from the siblings showed UV sensitivity, a
      failure of recovery of RNA synthesis (RRS) after UV-irradiation, and a normal
      level of unscheduled DNA synthesis (UDS), which were, unexpectedly, the
      biochemical characteristics usually associated with Cockayne syndrome (CS).
      However, no complementation group assignment in these cells has yet been
      performed. We here report that these patients can be assigned to CS
      complementation group B (CSB) by cell fusion complementation analysis. To our
      knowledge, these are the first patients with defects in the CSB gene to be
      associated with an XP phenotype. The results imply that the gene product from the
      CSB gene must interact with the gene products involved in excision repair and
      associated with XP.

PMID- 8566950
TI  - Genomic structure and PCR-SSCP analysis of the human CD40 ligand gene: its
      application to prenatal screening for X-linked hyper-IgM syndrome.
AB  - To develop a general method for analysis of the mutation and prenatal diagnosis
      of X-linked hyper-IgM syndrome (XHM), the human CD40 ligand (hCD40L) gene was
      cloned and sequenced with special reference to the 5' and 3' flanking regions and
      exon/intron boundaries. The hCD40L gene consists of five exons and four introns,
      as already reported by others. Two major transcription initiation sites were
      identified at 67 bp and 64 bp upstream from the ATG initiation codon. The hCD40L
      mRNA transcripts terminated at 321 bp, 327 bp and 987 bp downstream from the TGA
      stop codon. Based on the intronic sequences, oligonucleotide primers were
      designed for amplifying the coding region of each exon separately. Polymerase
      chain reaction--single-strand conformational polymorphism (PCR-SSCP) analysis was
      successfully applied to screening for the defective hCD40L gene in a family with
      XHM. The nonsense mutation, Trp140 (TGG)-->stop (TAG) in exon 5, was found in the
      mother and an affected child. We also performed prenatal diagnosis by PCR-SSCP
      during the first trimester of pregnancy in this family.

PMID- 8566951
TI  - Translocation breakpoints in three patients with campomelic dysplasia and
      autosomal sex reversal map more than 130 kb from SOX9.
AB  - Campomelic dysplasia (CMPD1) and autosomal XY sex reversal (SRA1) are caused by
      mutations in the SRY-related gene SOX9 on 17q. Unexpectedly, the 17q breakpoints
      in four CMPD1 translocation cases previously analyzed by us and others map 50 kb
      or more from SOX9. Here, we present clinical, cytogenetic, and molecular data
      from a new CMPD1/SRA1 patient with t(6;17)(q14;q24). Fluorescence in situ
      hybridization has shown that the 17q breakpoint in this case maps to the same
      region as the breakpoints in the other translocation cases, at least 130 kb from
      SOX9. Likewise, the breakpoints in two of the previously described cases also map
      more than 130 kb and, as shown by pulsed field gel electrophoresis analysis, at
      most 400 kb or 690 kb from SOX9. By using a SOX9 coding sequence polymorphism,
      expression of both SOX9 alleles has been demonstrated by the reverse
      transcriptase polymerase chain reaction in lymphoblastoid cells from one of the
      translocation cases.

PMID- 8566952
TI  - Identification of mutations in the ALD-gene of 20 families with
      adrenoleukodystrophy/adrenomyeloneuropathy.
AB  - Adrenoleukodystrophy (ALD), an X-linked inherited metabolic disorder, is the most
      frequent inborn peroxisomal disease. It leads to demyelination in the central and
      peripheral nervous system. Defective beta-oxidation of saturated very long chain
      fatty acids (VLCFAs; C22:0-C26:0) in peroxisomes has been shown to lead to an
      accumulation of VLCFAs in leukoid areas of the central nervous system, peripheral
      nerves, adrenal gland, and blood. The ALD gene has been recently identified and
      encodes a 745-amino-acid protein. We screened patients with
      adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN) from 20 kindreds for
      mutations in the ALD gene. Eleven missense and two nonsense mutations, five
      deletions, and one insertion were detected by direct sequencing of eight reverse
      transcribed fragments of the ALD-gene mRNA. Four mutations could be shown to be
      de novo. All mutations could be confirmed in carriers by sequencing genomic DNA.
      No correlation between the type of mutation and the severity of the phenotype
      could be observed. The mutations were not detected in the ALD gene of 30 healthy
      persons.

PMID- 8566953
TI  - Mutations in the iduronate-2-sulfatase gene in five Norwegians with Hunter
      syndrome.
AB  - We have identified the mutations in the iduronate-2-sulfatase (IDS) gene of five
      unrelated Norwegians with Hunter syndrome by reverse transcription-polymerase
      chain reaction (RT-PCR) analysis of IDS mRNA followed by single strand
      conformation polymorphism (SSCP) analysis and cDNA sequencing. One patient had a
      5-bp deletion, located at the intron 5/exon 6 junction, that created a new
      alternative splice site. This expanded the deletion to 9 bp in mRNA, an in-frame
      deletion of the first 3 codons of exon 6 of the IDS gene. In two patients point
      mutations were identified, the S333L mutation, which has been reported
      previously, and A346D (a C-->A transversion at nucleotide 1161/exon 8), which is
      novel. Two patients had large 3' mRNA rearrangements. The A346D mutation was
      associated with the mild phenotype, all others with the severe form.

PMID- 8566954
TI  - Familial adenomatous polyposis: a submicroscopic deletion at the APC locus in a
      family with mentally normal patients.
AB  - Cytogenetically visible deletions that include the adenomatosis polyposis coli
      (APC) locus have repeatedly been reported in mentally handicapped polyposis
      patients. We report on a family with a submicroscopic deletion of about 200 kb
      including more than the 3' half of the APC gene and the adjacent DP1 gene. The
      deletion was detected by linkage analysis with flanking and intragenic markers
      and proven by in situ hybridisation with intragenic cosmid clones. All the
      familial adenomatous polyposis (FAP) patients and persons at risk in the family
      show normal behaviour and intelligence. Thus, it is conceivable that at least
      some of the FAP patients in whom mutations could not be identified by routine
      methods may have large but submicroscopic deletions.

PMID- 8566956
TI  - Severe congenital limb deficiencies, vertebral hypersegmentation, absent thymus
      and mirror polydactyly: a defect expression of a developmental control gene?
AB  - We describe two unrelated patients with a complex malformation pattern that may
      be a candidate for a developmental gene disorder. These two patients had severe,
      symmetrical upper and lower limb deficiencies, vertebral hypersegmentation, and
      duodenal atresia. Patient 1 also had mirror-image polydactyly of his feet;
      patient 2 was athymic. The concurrence in two unrelated patients of additional
      vertebrae with severe anomalies in limb development, including a symmetrical
      deficiency of the four limbs and either mirror-image duplication of some toes
      (only in patient 1) or absence of the thymus (only in patient 2), represents an
      early alteration in body-plan organization. Since limb development, thymus
      development and segmentation are possibly under the control of homeobox genes in
      the human embryo, it seems reasonable that the malformations observed in these
      two patients resulted from a defect of a gene controlling developmental pattern
      formation, possibly a homeobox gene or a paired-box gene. Severe limb
      deficiencies have been reported in other well-known genetic entities, such as
      Roberts syndrome, Baller-Gerold syndrome, X-linked amelia, and DK-phocomelia
      syndrome. However, since the specific pattern of anomalies observed in these
      patients makes the diagnosis of some of the abovementioned disorders unlikely, we
      conclude that our patients have a previously undescribed disorder.

PMID- 8566955
TI  - Identification of four novel splice site mutations in the ornithine
      transcarbamylase gene.
AB  - Ornithine transcarbamylase (OTC) deficiency, the most common inborn error of the
      urea cycle, shows X-linked inheritance with frequent new mutations. Using
      polymerase chain reaction (PCR) amplification of the individual exons including
      adjacent intron sequences followed by direct sequencing of the amplimers we
      identified four new mutations affecting donor splice sites of introns 2, 5, 6,
      and 8. The mutation at the first position of intron 2 was a G to A exchange
      associated with acute neonatal hyperammonemia in a male patient at the age of 5
      months. A G to C substitution in intron 5 was detected in a boy who developed 2
      days after birth hypotonia, and respiratory distress, followed by severe
      hyperammonemia and terminal coma. The intron 6 mutation, a G to T substitution,
      was detected in a girl presenting with first episodes of vomiting and agitation
      at the age of 2 months. The mutation in intron 8, also a G to T transition,
      caused fatal hyperammonemia and early death at the age of 15 days in a male
      patient. We present four donor splice site mutations resulting in severe neonatal
      or very early onset of the disease in three boys and in one female patient. As
      the GT dinucleotide of the 5' donor splice site is invariant and required for
      correct splicing the described mutations may lead to improperly spliced mRNAs and
      aberrant gene products.

PMID- 8566957
TI  - Trisomy of human chromosome 18: molecular studies on parental origin and cell
      stage of nondisjunction.
AB  - We investigated the parent and cell division of origin of the extra chromosome 18
      in 62 aneuploids with a free trisomy 18 by using chromosome-18-specific
      pericentromeric short-sequence repeats. In 46 cases, DNA of patients was
      recovered from archival specimens, such as paraffin-embedded tissues and fixed
      chromosomal spreads. In 56 families, the supernumerary chromosome was maternal in
      origin; in six families, it was paternal. Among the 56 maternally derived
      aneuploids, we could exclude a postzygotic mitotic error in 52 cases. Among those
      in which the nondisjunction was attributable to an error at meiosis, 11 were the
      result of a meiosis I nondisjunction and 17 were caused by a meiosis II error.
      This result differs markedly from findings in acrocentric chromosomes where
      nondisjunction at maternal meiosis I predominates. Among the six paternally
      derived cases, two originated from a meiotic error, indicating that a
      nondisjunction in paternal meiosis is not as rare as previously suggested.

PMID- 8566958
TI  - A missense mutation in the NF2 gene results in moderate and mild clinical
      phenotypes of neurofibromatosis type 2.
AB  - Since the identification of the NF2 tumor suppressor gene in 1993, various
      mutations have been found in NF2-related tumors and in lymphocytes from NF2
      patients. Most of the reported mutations result in truncated gene products.
      Missense mutations affecting the tumor suppressor are rare. These missense
      mutations would provide valuable information for the understanding of the
      function of the tumor suppressor, since they should affect critical parts of the
      protein. In this study we describe a novel point mutation in exon 15 of the NF2
      gene, which is found in lymphocyte DNA of two NF2 patients from one family. This
      mutation is expected to result in a substitution of Pro for Gln at codon 538.
      Though both of the two patients developed bilateral vestibular schwannomas, the
      first patient showed onset of the disease at the age of 31 years and presented
      with various central, peripheral and abdominal tumors, while the second patient
      showed later onset of clinical symptoms (at age 52 years) and presented with only
      two additional small spinal tumors.

PMID- 8566959
TI  - A new highly polymorphic marker in the 5' untranslated region of HLA-F shows
      strong allelic association with haemochromatosis.
AB  - The 5' untranslated region of HLA-F contains a polypurine tract comprising
      repeats of tri- and hexa-nucleotide motifs. We have recently demonstrated that
      this polypurine tract is highly polymorphic by using the polymerase chain
      reaction. Here, we demonstrate that some of the alleles can be explained by a
      deletion of approximately 100 bp DNA and show that alleles of this novel, highly
      polymorphic locus are as strongly associated with haemochromatosis as HLA-A3 or
      D6S105-8. The observed frequency of heterozygosity at HLA-RF is extremely high
      (95%) and this locus has been found to be informative in pedigrees that are non
      informative at HLA-A and D6S105. We also show an example of replication slippage
      at HLA-F in one pedigree.

PMID- 8566960
TI  - Expression and regulation of the dystrophin Purkinje promoter in human skeletal
      muscle, heart, and brain.
AB  - Dystrophin mRNA transcripts from the P (Purkinje) promoter were shown to be
      differentially expressed in human skeletal muscle, heart, and brain. The
      expression pattern was characteristic of tissue type and developmental stage.
      Polymerase chain reaction (PCR) analysis of the P promoter transcripts in adult
      skeletal muscle and adult brain identified two alternatively spliced sequences,
      one that encodes a full-length dystrophin mRNA and a second that transcribes a
      termination codon 27 nucleotides (8 amino acids) after the ATG initiation site.
      Alternative splicing of this truncated coding transcript was developmentally
      regulated, and it was expressed as the major form in adult cortical brain and
      adult heart. The biological significance of this peptide remains unclear. The
      full-length transcript was the major form in fetal cortical brain and adult
      skeletal muscle. Ribonuclease protection assay demonstrated that as much as 20%
      of dystrophin transcription in normal adult skeletal muscle was derived from the
      full-length transcript from the P promoter. In contrast, adult heart did not
      express significant levels of P promoter derived transcripts. Thus, transcripts
      from the P promoter were found to be developmentally regulated in the brain, and
      its activity was differentially expressed in skeletal versus cardiac muscle
      tissues. These data show that the P promoter transcript displays a broader scope
      of expression, regulation, and complexity than previously appreciated.

PMID- 8566961
TI  - Clonality of tuberous sclerosis harmatomas shown by non-random X-chromosome
      inactivation.
AB  - Tuberous sclerosis (TSC) is an autosomal dominant condition characterised by
      tumour-like malformations (hamartomas) in the brain and other organs. A
      proportion of hamartomas from patients with TSC show loss of heterozygosity (LOH)
      for DNA markers in the region of either the TSC1 gene on chromosome 9q34 or the
      TSC2 gene on 16p13.3. This implies that these lesions are clonal. We have studied
      X-chromosome inactivation, as a marker of clonality, in 13 hamartomas from
      females with TSC. The hamartomas comprised five renal angiomyolipomas, three
      fibromas and seven other lesions. In previous studies, four of the lesions showed
      LOH. A polymerase chain reaction assay was used to analyse differential
      methylation of an HpaII restriction site adjacent to the androgen-receptor
      triplet-repeat polymorphism on Xq11-12. In 12 of the lesions, there was a skewed
      inactivation pattern with one X chromosome being fully methylated and the other
      unmethylated. Normal tissue showed a random pattern of inactivation. These data
      confirm that most TSC hamartomas are clonal in origin. This is an intriguing
      finding, since these lesions are composed of more than one cell type.

PMID- 8566962
TI  - Psychosis and genes with trinucleotide repeat polymorphism.
AB  - Abnormal expansion of genes with trinucleotide repeat (TNR) polymorphism has been
      found in a number of neuropsychiatric disorders. These disorders and the major
      psychoses, schizophrenia and bipolar affective disorder, appear to share an
      interesting phenomenon: genetic anticipation. Because TNR expansion correlates
      with anticipation, these unstable DNA sites are considered important candidate
      loci for the major psychoses. We investigated genes with TNR polymorphisms,
      including B1, B33, B37, and the N-cadherin gene, in unrelated Caucasian North
      American and Italian schizophrenics (n = 53 to 74), and matched controls. Also,
      unrelated Caucasian North American patients with bipolar I affective disorder
      were screened for the B33 and N-cadherin genes (n = 49 and 63, respectively). No
      unusually long alleles that would suggest abnormal expansion of the TNR were
      observed for any of these genes. Also, no statistically significant results were
      found in tests for genetic association between any of these genes and
      schizophrenia. For B37, a trend toward a difference in allele counts between
      schizophrenics and controls was observed. However, no clear evidence for a role
      of these TNR-containing genes in schizophrenia or bipolar affective disorders was
      found.

PMID- 8566963
TI  - X chromosome inactivation in 30 girls with Rett syndrome: analysis using the
      probe.
AB  - Rett syndrome (RS) is a neurologic disorder with an exclusive incidence in
      females. A nonrandom X-inactivation could provide insight into the understanding
      of this disease. We performed molecular analysis based on the differential
      methylation of the active and inactive X with probe M27 beta, taking into account
      the parental origin of the two Xs, in 30 control girls, 8 sisters, and 30 RS
      girls. In 27 control an 31 RS mothers, the inactivation status of the X
      transmitted to their daughters was also analyzed. The results showed a
      significantly increased frequency of partial paternal X inactivation (> 65%) in
      lymphocytes from 16/30 RS compared with 4/30 controls (P = 0.001). These results
      do not support the hypothesis of a monogenic X-linked mutation but should be
      taken into account when researching the etiology of this disease.

PMID- 8566964
TI  - CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC mutations.
AB  - Hereditary nonpolyposis colon cancer (HN-PCC) is an autosomally inherited
      predisposition to cancer that has recently been linked to defects in the human
      mismatch repair genes hMSH2 and hMLH1. The identification of the causative
      mutations in HNPCC families is desirable, since it confirms the diagnosis and
      allows the carrier status of unaffected relatives at risk to be determined. We
      report six different new mutations identified in the hMSH2 and hMLH1 genes of
      Russian and Moldavian HNPCC families. Three of these mutations occur in CpG
      dinucleotides and lead to a premature stop codon, a splicing defect or an amino
      acid substitution in an evolutionary conserved residue. Analysis of a compilation
      of published mutations including our new data suggests that CpG dinucleotides
      within the coding regions of the hMSH2 and hMLH1 genes are hotspots for single
      base-pair substitutions.

PMID- 8566965
TI  - The murine homolog of the human breast and ovarian cancer susceptibility gene
      Brca1 maps to mouse chromosome 11D.
AB  - The recently cloned human breast and ovarian cancer susceptibility gene, BRCA1,
      is located on human chromosome 17q21. We have isolated murine genomic clones
      containing Brca1 as a first step in generating a mouse model for the loss of
      BRCA1 function. A mouse genomic library was screened using probes corresponding
      to exon 11 of the human BRCA1 gene. Two overlapping mouse clones were identified
      that hybridized to human BRCA1 exons 9-12. Sequence analysis of 1.4 kb of the
      region of these clones corresponding to part of human exon 11 revealed 72%
      nucleic acid identity but only 50% amino acid identity with the human gene. The
      longest of the mouse Brca1 genomic clones maps to chromosome 11D, as determined
      by two-color fluorescence in situ hybridization. The synteny to human chromosome
      17 was confirmed by cohybridization with the mouse probe for the NF1-gene. This
      comparative study confirms that the relative location of the BRCA1 gene has been
      conserved between mice and humans.

PMID- 8566966
TI  - HbF-Lesvos: an HbF variant due to a novel G gamma mutation (:G gamma 75 ATA-
      >ACA) detected in a Greek family.
AB  - A T-->C substitution at position 402 of the G gamma globin gene results in an
      isoleucine to threonine substitution at codon 75 of the G gamma globin chain and
      the formation of HbF-Lesvos [alpha2 G gamma2 75 (E19) Ile-->Thr].

PMID- 8566967
TI  - Population study of the G1691A mutation (R506Q, FV Leiden) in the human factor V
      gene that is associated with resistance to activated protein C.
AB  - The mutation G1691A (R506Q) in the human factor V gene is associated with the
      resistance to activated protein C (APC) that represents a major risk of
      development of venous thrombosis. A population study of 180 unrelated individuals
      from south Germany was performed. Examination of the allelic frequencies revealed
      a high prevalence of this disease-related mutation (Q506, FV Leiden). The
      heterozygosity rate was 7.8% with a confidence interval between 4% and 11%.

PMID- 8566968
TI  - A missense mutation (Thr-6Pro) in the lysosomal acid lipase (LAL) gene is present
      with a high frequency in three different ethnic populations: impact on serum
      lipoprotein concentrations.
AB  - A frequent missense mutation (Thr-6Pro) found in the prepeptide of the lysosomal
      acid lipase (LAL) gene was analyzed in a cohort of 1003 randomly selected samples
      from Germany, Japan and Sardinia (Italy). Using the mutagenically separated
      polymerase chain reaction (MS-PCR), allele frequencies of 0.269, 0.238 and 0.245
      were determined in the three populations, respectively. Statistical analysis
      showed a lack of association with a dyslipidemic phenotype in all three groups.
      Additionally, in a subgroup of 126 German individuals no association was observed
      between genotype and LAL activity. We conclude that this mutation appears to be a
      frequent LAL gene polymorphism causing no impaired function of the enzyme and no
      measurable dyslipidemia in the general population.

PMID- 8566969
TI  - Yaws in Ecuador: impact of control measures on the disease in the Province of
      Esmeraldas.
AB  - OBJECTIVES: To determine the impact of a community-based programme of yaws
      control in Esmeraldas province in Ecuador. METHODS: Community health workers
      provided mass treatment and subsequent surveillance for the detection and
      treatment of new cases and their contacts over the period 1988 to 1993. Clinical
      and serological surveys were performed in the study area in 1988 and 1993.
      RESULTS: Over the 5 year observation period, the number of communities with
      active infections had decreased by 75%, from 20 communities in 1988 to 5 in 1993.
      In 1993, 4 communities were found free of clinical infections as well as latent
      infections. There was a corresponding decrease of 94.6% in the prevalence of
      dermal lesions (from 11.2% to 0.6%), and a reduction of 97.3% in latent
      infections (from 93.6% to 2.5%). CONCLUSIONS: The control of yaws using existing
      community-based health workers has proved very effective in Ecuador.

PMID- 8566970
TI  - Seroprevalence of syphilis amongst pregnant women attending antenatal clinics in
      a rural hospital in north west Ethiopia.
AB  - OBJECTIVE: To determine the seroprevalence of syphilis in pregnant women
      attending antenatal care clinics in a rural hospital in Ethiopia and describe
      their characteristics so that timely and effective care can be offered. SUBJECTS:
      Pregnant women attending antenatal care clinics at a rural hospital. METHODS: A
      cross sectional study was conducted at a rural hospital in north west Ethiopia in
      September 1994. Data were collected on socio demographic characteristics and past
      history of sexually transmitted diseases of antenatal care attenders from the
      records of the hospital. Sera from these pregnant women were examined for
      syphilis using the VDRL test. VDRL positivity was cross tabulated with socio
      demographic variables and past history of sexually transmitted diseases. RESULTS:
      Two hundred and seventy pregnant women were included in the study. Median age of
      the respondents was 25.2 years. A substantial majority were orthodox Christians
      (97.4%) and married (92.6%). Town dwellers constituted 58.2% of the antenatal
      care attenders. Only 4.7% of the women started attending antenatal care clinics
      during the first trimester. Thirty seven women (13.7%) were found to be VDRL
      positive. Past history of sexually transmitted diseases was significantly
      associated with VDRL positivity (p < 0.05). CONCLUSIONS: High VDRL positivity
      rate is observed in this study. Certain risk factors may be responsible for
      current and past episodes of sexually transmitted diseases. There is a need for
      improvement of antenatal care activities at different levels of health care.
      Appropriate strategies should be devised for prevention and control of sexually
      transmitted diseases in women of reproductive age groups and the general
      population.

PMID- 8566971
TI  - Risk behaviour and STD acquisition in genitourinary clinic attenders who have
      travelled.
AB  - OBJECTIVE: To investigate the travel history of clients presenting at a
      genitourinary medicine (GUM) clinic in order to assess the contribution made by
      sexual partnerships abroad to STD transmission in the UK. SUBJECTS: 386 old and
      new clients who attended during a 3-month period and who had travelled abroad in
      the 3 months preceding their visit. METHODS: All participating clients self
      completed a confidential questionnaire, the results of which were then linked to
      their clinical diagnosis (if any). RESULTS: 25% of participants reported a new
      sexual partner during their most recent trip abroad. In comparison to those not
      reporting a new partner, they were more likely to be male, travelling alone, to
      have visited the clinic previously and to have no regular sexual partner. Two
      thirds reported never or inconsistently using condoms with these new partners. A
      total of 11.6% of the STDs diagnosed in the study participants may have been
      acquired abroad. CONCLUSION: We have found a high rate of new sexual
      relationships reported by attendees at our GUM clinic, and a low rate of reported
      condom use. With high HIV incidence rates in many tourist regions, the need for
      further studies to establish the true extent of imported STDs in the UK is a
      priority, and primary prevention campaigns to inform travellers are of paramount
      importance.

PMID- 8566972
TI  - Response to influenza immunisation in asymptomatic HIV infected men.
AB  - OBJECTIVE: This study aimed to determine if patients with HIV infection can
      develop a significant antibody response to influenza immunisation, and whether
      such immunisation is detrimental to the progression of their HIV illness. DESIGN:
      Prospective, non-randomised study. METHODS: The titres of antibody response to
      influenza immunisation were determined in 44 asymptomatic HIV positive men and
      compared with 16 HIV presumed seronegative controls. The magnitude of response
      were correlated with patients' CD4 lymphocyte counts. The rate of CD4 lymphocyte
      count decline over a median of 12 months before and after immunisation were also
      evaluated. RESULTS: Thirty-two of the 44 HIV positive subjects (73%) were able to
      mount a four-fold or greater response to at least one of the influenza strains,
      and 14 of them (32%) did so to all four strains. In comparison, 15 of the 16
      controls (93.5%) had a four-fold or greater response to at least one, and six of
      them (38%) to all influenza strains, which was not significantly different from
      the HIV positive group. The magnitude of increase in antibody titre was not
      significantly different between the two groups either. CD4 lymphocyte count
      change for a median of 12 months after immunisation was not different from a
      median of 12 months before immunisation. CONCLUSIONS: Asymptomatic HIV infected
      patients are able to mount antibody response to influenza immunisation, which
      appears to be safe in respect to HIV illness progression in the short term.

PMID- 8566973
TI  - AIDS in Africans living in London.
AB  - OBJECTIVES: To investigate the presentation of HIV infection and AIDS amongst
      Africans diagnosed with AIDS living in London. METHODS: Identification of all
      AIDS cases of African origin attending four HIV specialist centres in South
      London--Guy's, King's, St George's and St Thomas' Hospitals--up to March 1994, by
      retrospective review of case notes of all HIV positive patients. RESULTS: Of 86
      patients (53 women, 33 men) studied, 59 (69%) were from Uganda. The most frequent
      AIDS-defining diagnoses were: Pneumocystis carinii pneumonia (PCP) 21%,
      tuberculosis (TB) 20% (extrapulmonary TB 14%, pulmonary TB 6%), cerebral
      toxoplasmosis 14%, oesophageal candida 13%, cryptococcal meningitis 11%, wasting
      6%, herpes simplex infection > 1 month 5%, Kaposi's sarcoma 5%, other 6%.
      Cytomegalovirus retinitis was diagnosed in one case. Late presentation was
      common; 70% were diagnosed HIV positive when admitted to hospital. The diagnosis
      of AIDS was coincident with a first positive HIV test result in 61%. The mean CD4
      counts at both HIV and AIDS diagnoses were similar in both men and women: 87 x
      10(6)/l and 74 x 10(6)/l in men and 99 x 10(6)/l and 93 x 10(6)/l in women
      respectively. Overall, TB 21 (24%) (extrapulmonary TB 12, pulmonary TB 9) was
      either the AIDS-defining diagnosis or was detected within three months of this
      event. Sixty-two per cent of TB cases were diagnosed within twelve months of
      entry to the UK compared to 34% of all other AIDS cases. The prevalence of STD
      was very low; genital herpes was the commonest STD: 17% of the women, 9% men; 28%
      of the men and 11% of the women tested had a positive TPHA test. In cases known
      to be HIV-positive prior to an AIDS diagnosis, 41% took prophylaxis for PCP and
      45% had taken zidovudine (ZDV). Forty two of the study participants had 89
      children: 59 of these children had mothers in the study. Overall, 37 (42%) of the
      children had lost at least one parent at the time of data assessment.
      CONCLUSIONS: PCP and TB were the most common initial AIDS-defining diagnoses. The
      majority of TB cases were diagnosed within 12 months of entry to the UK. An AIDS
      defining diagnosis was the first manifestation of HIV-related illness in the
      majority of patients. Because of late presentation to medical services, access to
      treatments for HIV infection and prophylaxis against opportunistic infections was
      limited. Extending the role of clinics and staff into the community might
      facilitate both earlier presentation and access to services. Future provision of
      local services will need to be sensitive to the requirements of individuals from
      different cultures and backgrounds.

PMID- 8566974
TI  - Differentiation of Neisseria gonorrhoeae strains by polymerase chain reaction and
      restriction fragment length polymorphism of outer membrane protein IB genes.
AB  - OBJECTIVES: To employ polymerase chain reaction (PCR) and restriction fragment
      length polymorphism (RFLP) analysis for the rapid differentiation of Neisseria
      gonorrhoeae protein IB (PIB) isolates and to compare its usefulness with the
      widely accepted auxotype/serovar classification scheme. METHODS: The outer
      membrane protein IB genes of 47 gonococcal isolates belonging to 10 different
      serovars were amplified by PCR. The approximately 1 kb DNA products were then
      digested separately with restriction enzymes CfoI and MspA1I, and electrophoresed
      on agarose gels. RESULTS: Cleavage of PIB genes by MspA1I and CfoI differentiated
      all the N gonorrhoeae strains into five and six PCR-RFLP profiles, respectively.
      PCR-RFLP was more discriminatory than auxotyping, which classifies the strains
      into only two auxotypes. Some strains belonging to common serovars could be
      further differentiated. A combination of PCR-RFLP analysis, auxotyping and
      serotyping further increased the discrimination of the strains into 34 subtypes.
      The PCR-RFLP method was easy to perform, reliable, reproducible, and consistent
      with published nucleotide sequence data. CONCLUSION: The PCR-RFLP method can
      augment auxotyping and serotyping or be used as a preliminary screening tool to
      differentiate N gonorrhoeae strains in areas where serotyping reagents are not
      easily available.

PMID- 8566975
TI  - Serovar specific immunity to Neisseria gonorrhoeae: does it exist?
AB  - OBJECTIVE: To determine whether the host immune response to gonorrhoea provides
      limited serovar specific protection from reinfection. SUBJECTS: 508 episodes of
      gonorrhoea diagnosed at a city centre genitourinary medicine clinic including 22
      patients with multiple infections over a 4 year period. METHODS: Patients with
      recurrent gonococcal infection were analysed with respect to the initial and
      subsequent serovars isolated. RESULTS: No significant difference was seen in the
      prevalence of serovars isolated following a repeat infection compared with those
      without repeat infections. The site of the initial infection did not appear to
      influence the subsequent serovar isolated. CONCLUSION: We found no evidence of
      serovar specific immunity in our population. It remains possible that populations
      with a higher prevalence of gonorrhoea and more frequent infections may have a
      quantitatively greater immune response.

PMID- 8566976
TI  - Diagnostic efficacy of chlamydial antibodies in cervical secretions from pregnant
      women and adolescent girls.
AB  - OBJECTIVE: To assess the prevalence of cervical antibodies to Chlamydia
      trachomatis in two different populations and to correlate the findings to
      culture, direct fluorescent antibody test (DFA) and serum antibodies. SETTING:
      Antenatal clinics and clinic for teenage counselling in Gavle. PATIENTS: 1078
      pregnant women attending for routine follow up in the third trimester of
      pregnancy and 256 teenage girls. OUTCOME MEASURES: Cervical IgG and IgA
      antibodies to Chlamydia trachomatis. Cervical cultures for chlamydia. Serum IgG
      antibodies. DFA tests were used only in the teenage group. RESULTS: The
      prevalence of positive culture was 2.0% in pregnant women and 8.6% in teenage
      girls. In pregnant women cervical IgG > or = 8 and IgA > or = 8 were found in
      7.2% and 5.8% respectively and in teenage girls in 6.6% and 2.0% respectively.
      The agreement between cervical IgG > or = 8 and humoral IgG > or = 32 was 0.76 in
      the pregnant group and 0.95 in the teenage group. The sensitivity, specificity
      and positive predictive value (PPV) for cervix IgG > or = 8 to predict a positive
      culture was 0.64, 0.94 and 0.18 respectively in pregnant women and 0.41, 0.97,
      0.53 respectively in teenage girls. Of 31 teenage girls with either positive
      culture or positive DFA 12 had cervical IgG > or = 8 while five of 225 with
      negative chlamydia tests had cervical IgG > or = 8 (sensitivity 0.40 and PPV of
      0.71). Cervical IgG > or = 16 was found in eight of 31 with positive chlamydia
      tests and in one of 225 with negative tests (sensitivity 0.26 and PPV 0.89).
      CONCLUSIONS: The finding of cervical IgG > or = 16 predicts current chlamydia
      (culture or DFA) in nearly 90% in a teenage population. It might indicate current
      infection in spite of negative culture in some cases. For low titres and in a low
      prevalence pregnant population cervical IgG are not useful for the diagnosis of
      chlamydia. As the sensitivity is low cervical antibodies cannot be used for
      screening purposes.

PMID- 8566977
TI  - Development and evaluation of screening strategies for Chlamydia trachomatis
      infections in an STD clinic.
AB  - OBJECTIVES: To identify predictors for Chlamydia trachomatis infection among
      visitors of an STD clinic in Amsterdam in 1986-1988. To design predictor-based
      screening programmes for C trachomatis. To evaluate the chosen screening strategy
      in 1993. METHODS: In 1986-1988, 947 heterosexual men and 648 women participated
      in the study. A medical history was recorded, a physical examination took place
      and samples were taken for laboratory diagnostics. Information for 1993 was
      available from routine databases. RESULTS: C trachomatis infections in
      heterosexual men in 1986-1988 (prevalence 15.8%) were independently associated
      with: age under 26 years, being an STD contact, coitarche below 13, last sexual
      contact with a non-prostitute, (muco)-purulent urethral discharge and ten or more
      leukocytes per microscopic field of urethral smear or urine. For women
      (prevalence 21.5%) independent predictors were age under 26, no history of STD,
      being an STD contact, cervical friability, (muco)purulent cervical discharge,
      presence of clue cells and ten or more leukocytes per field of urethral smear.
      Screening men with one anamnestic predictor for C trachomatis and ten or more
      leukocytes in smear or urine (59% of men) would detect 93% of the cases in 1986
      1988. For females only universal screening proved to be suitable. After the
      introduction of a screening strategy in 1989 (universal for women, indicated by
      urethritis for men), a strong decline was found in the C trachomatis prevalence
      for all subgroups in 1993, excluding prostitute's clients and Turkish men.
      CONCLUSIONS: In 1993 the overall C trachomatis prevalence had declined among the
      attendants of the STD clinic. It seems likely that this fall was caused both by
      the screening programme and the reduction of risk behaviour.

PMID- 8566978
TI  - Detection of Chlamydia trachomatis by ligase chain reaction compared with
      polymerase chain reaction and cell culture in urogenital specimens.
AB  - OBJECTIVE: The aim of this study was to evaluate the newly developed ligase chain
      reaction (LCR) assay for the detection of Chlamydia trachomatis in urogenital
      specimens using cell culture and Amplicor PCR for comparison. SUBJECTS: Two
      hundred and eighty patients attending hospital or urban STD clinics (high-risk
      population, 62 men and 84 women) and obstetric/gynaecology clinics (low-risk
      population, 134 women) in Bordeaux, France. METHODS: Specimens from men were
      tested with LCR on urethral swabs and urine, with Amplicor or urine, with cell
      culture on urethral swabs. Specimens from women were tested with LCR, Amplicor
      and cell culture on endocervical swabs and with LCR on urine. When the three
      methods generated different results, the LCR and Amplicor tests were repeated on
      the remaining samples. Samples with discordant LCR and Amplicor results and a
      negative culture were further analysed by major outer membrane protein gene omp1
      PCR. RESULTS: After analysis of discrepant results, the overall prevalence was
      7.5% (21/280) calculated on the basis of an expanded "gold standard" defined as
      culture positive or LCR plus Amplicor positive or omp1-PCR positive for
      discrepant results between LCR and Amplicor tests. Of the 21, 20 were detected by
      LCR, 17 by Amplicor and culture. The specificity of LCR and Amplicor was 99.6%.
      CONCLUSION: The LCR Chlamydia trachomatis test is a highly sensitive nonculture
      technique and a good alternative test for the detection of chlamydial infections.

PMID- 8566979
TI  - Topical treatment of genital warts in men, an open study of podophyllotoxin cream
      compared with solution.
AB  - OBJECTIVE: To evaluate the clinical efficacy of a 0.15% and a 0.3% cream
      formulation of podophyllotoxin in comparison with the 0.5% solution in the
      treatment of condylomata acuminata and to compare the treatment modalities
      regarding side effects. DESIGN: The study was designed as an open randomised
      trial. Ninety male patients with signs of penile HPV infection, with either
      acuminate or papular lesions, were randomised into three parallel treatment
      groups. The study medication comprised 0.15% and 0.3% cream and 0.5% solution of
      podophyllotoxin. The patients treated themselves twice daily for three
      consecutive days and if total regression of the warts was not achieved after this
      first treatment cycle, further treatment cycles at 7-day intervals were to be
      repeated up to a maximum of four treatments. SETTING: The study was carried out
      in three outpatient clinics: two STD clinics, Department of Dermatology and
      Venereology, University Hospital (45 patients) and Institut Antoine Fournier,
      Paris (30 patients), and one military hospital, S1/FO 47/48, Sjukhusenheten,
      Enkoping (15 patients). RESULTS: Statistical evaluation of the treatment effect
      was based on a "Response rate" calculation at each visit. The number of
      completely responding patients after the first, second, third and fourth cycle
      were 40 (44%), 61 (68%), 67 (74%) and 70 (78%), respectively. There was no
      statistically significant difference between the three treatments after four
      treatment cycles. However, the 0.15% cream had a significantly slower onset of
      efficacy as compared with the 0.3% cream and 0.5% solution. Adverse effects were
      less severe and less frequent with the 0.15% cream than with the other treatment
      modalities. Severe adverse effects were reported by 12 patients, of whom two were
      treated with 0.15% cream, five with 0.3% cream and five with 0.5% solution.
      Thirty-one patients were completely free from adverse effects. CONCLUSION: In
      this open randomised study with three parallel treatment groups, two cream
      formulations of 0.15% and 0.3% podophyllotoxin and a 0.5% solution of the same
      drug all showed an equally good response rate after four treatment cycles.
      Reported adverse effects were few and mild. The convenience of having different
      formulations to offer when prescribing treatment for condylomata must be
      considered.

PMID- 8566980
TI  - A single-blind study of podophyllotoxin cream 0.5% and podophyllotoxin solution
      0.5% in male patients with genital warts.
AB  - OBJECTIVE: To evaluate the efficacy-safety ratio of a new topical podophyllotoxin
      cream 0.5% compared with podophyllotoxin solution 0.5% (Condyline) in male
      patients with genital warts. METHODS: In an observer-blinded controlled study a
      total of 136 and 133 wart lesions were treated with podophyllotoxin cream 0.5%
      and podophyllotoxin solution 0.5%, respectively. The preparations were applied
      twice daily for 3 days, repeated with 4 days intervals for a minimum of two and a
      maximum of four treatment cycles. RESULTS: At the conclusion of the study (8
      weeks after completion of therapy) a significant reduction in mean wart area was
      observed in both the cream group (87.7, SD 8.4 to 20.6, SD 2.7) and in the
      solution group (92.3, SD 7.5 to 21.5, SD 2.8) (p < 0.01). At the same time all
      treated warts had completely cleared in 63% of patients in both study groups.
      Mild to moderate side effects occurred to the same extent in both podophyllotoxin
      cream and podophyllotoxin solution recipients. CONCLUSION: We conclude that
      podophyllotoxin 0.5% administered in a cream formulation does not give additional
      clinical benefits when compared with podophyllotoxin solution 0.5% in male
      patients with external genital warts.

PMID- 8566981
TI  - Why do patients default from follow-up at a genitourinary clinic?: a multivariate
      analysis.
AB  - OBJECTIVE: Firstly to compare the proportion of patients defaulting from follow
      up at a genitourinary medicine clinic with those attending other hospital based
      clinics. Secondly to determine which factors are associated with non attendance
      at a city centre genitourinary medicine clinic. METHODOLOGY: The proportion of
      patients who defaulted at a genitourinary medicine clinic, a general medical
      clinic, a general surgical clinic and a dermatology clinic during March 1995 were
      compared. A multivariate logistic regression analysis was performed comparing
      attenders and non attenders at the genitourinary medicine clinic with respect to
      time of appointment, diagnosis, previous contacts with clinic staff, potential
      domestic commitments and patient demographics in a prospective case control
      study. RESULTS: The default rate at the genitourinary medicine clinic was 15%
      compared with 13%, 15% and 14% for medical, surgical and dermatology clinics
      respectively. Patients who defaulted from the genitourinary medicine clinic (167)
      were compared with 172 attenders and significant differences found for timing of
      appointments, area of residence, frequency of counselling by the health advisor
      and age of the patient. Other factors such as the diagnosis, whether a woman had
      children, sexual orientation, whether negative results had been given over the
      phone, source of referral, sex of patient, employment status and the weather were
      not found to be significantly associated with defaulting from an appointment.
      CONCLUSIONS: The time of the appointment and being seen by a health advisor were
      the only variables identified over which the clinic has control and therefore
      could potentially reduce non attendance rates.

PMID- 8566982
TI  - "Healthy alliances?"--other sexual health services and their views of
      genitourinary medicine.
AB  - OBJECTIVE: To assess health professionals' views of genitourinary medicine (GUM)
      services in a large UK city and to determine potential intervention measures for
      change. METHODS: A postal questionnaire was sent to 205 service providers in a
      range of sexual health services in Glasgow, including GUM specialist doctors,
      nurses and health advisers. The questionnaire included structured questions about
      organisation and use of GUM services, assessment of profile and stigma, and asked
      about factors most likely to influence future service development. RESULTS: 128
      questionnaires were returned from areas throughout the city. Non-GUM health
      professionals had poor factual knowledge about the organisation of GUM services.
      GUM had a poor profile compared with other sexual health services and stigma was
      thought to exist about the service. Most non-GUM service providers continue
      traditionally to regard GUM mainly as a referral centre for a few specific
      sexually transmitted infections and not as a centre for holistic sexual health
      care. Genital chlamydial infection and pelvic inflammatory disease were
      considered low priority for GUM referral by some groups of service providers.
      These views contrasted with those working in the speciality. There was generally
      poor professional contact between GUM and other service providers involved in
      sexual health. Most indicated that greater levels of information and publicity,
      increased professional contact, and a broader range of services within GUM were
      important for future service development. CONCLUSIONS: The response to the
      questionnaire strongly indicates that there is poor awareness of and consequently
      suboptimal use of the full range of services offered by GUM. Potential
      interventions to address this need include increased cross-speciality
      collaboration and targeting of specific groups of service providers involved in
      sexual health care. Important groups include hospital-based specialists and
      voluntary agencies as well as general practitioners. There is a clear need to
      project the broad range of sexual health services offered by GUM, and to
      emphasise the role of GUM in managing specific sexual health problems including
      several sexually transmitted infections.

PMID- 8566983
TI  - How common is self-treatment in non gonococcal urethritis?
AB  - OBJECTIVE: To assess the prevalence of self-treatment in men with new episode non
      gonococcal urethritis (NGU). METHOD: Three hundred consecutive men with new
      episode NGU attending an open access genitourinary medicine clinic were
      interviewed using a semi-structured questionnaire. Details of treatment used
      before attending the clinic were obtained. RESULTS: Thirty (10%) men had used
      treatment, for an average of 7 days, prior to the clinic attendance. Agents used
      included antibiotics (11), savion or iodine (4), vitamin tablets (4), cisapride
      (2), local anaesthetic gel (2), antiseptic cream (2), cod liver oil (1), ferrous
      sulphate (1), naproxen (1), clotrimazole cream (1) and a poultice (1). Over 70%
      of the men reporting antibiotic use had self-medicated and in one case a fixed
      drug eruption had ensued. CONCLUSION: A significant number of men with NGU self
      treat. In addition to the adverse effects of such treatment and the potential
      effect on culture tests, clinic attendance may be postponed, the use of
      appropriate therapy delayed, and sexual contacts will remain at risk. Early
      attendance for treatment and contact tracing is essential and should be actively
      promoted.

PMID- 8566984
TI  - Serum antibodies to Trichomonas vaginalis in invasive cervical cancer patients.
AB  - OBJECTIVE: To evaluate, by seroepidemiology, the possible role of the sexually
      transmitted flagellate, Trichomonas vaginalis, in invasive cervical cancer.
      SUBJECTS AND METHOD: Sera from 121 invasive cervical cancer patients and 242
      random age-matched female controls. Antibodies to T. vaginalis were detected by
      the western blot technique. RESULTS: Antibodies to T. vaginalis were detected in
      the sera of 41.3% (50/121) of invasive cervical cancer patients compared with
      only 5.0% (12/242) of female controls. All the reactive sera reacted strongly
      with the immunogenic surface membrane proteins of T. vaginalis of molecular
      weights of about 92 and 115 kDa, with variable reactivity to other immunogenic
      proteins of T. vaginalis. CONCLUSION: The significantly increased relative risk,
      RR = 3.42 (95% CI = 1.73-6.78), is comparable to the RRs derived in
      seroepidemiological studies of human papillomavirus, suggesting that T. vaginalis
      may be even more closely associated with invasive cervical cancer than previously
      realized.

PMID- 8566985
TI  - Prevalence of Trichomonas vaginalis in a male sexually transmitted disease clinic
      population by interview, wet mount microscopy, and the InPouch TV test.
AB  - OBJECTIVE: To determine the prevalence of trichomoniasis in male patients from
      their urine at a Sexually Transmitted Disease (STD) Clinic using the InPouch TV
      culture system. METHODS: Two hundred and four patients were examined for STD
      infections. Their ages ranged between 17 and 72 years. Depending on their
      clinical symptoms tests were ordered for Neisseria gonorrhoeae, chlamydia, and
      for syphilis. Each patient submitted a clean catch urine specimen for trichomonas
      testing. A 15 ml aliquot of urine was centrifuged and a drop of the sediment
      examined microscopically. The remainder was cultured in the InPouch TV test. Each
      pouch was examined at 24 h, 48 h, and 5 days. RESULTS: Twenty-four of the 204
      patients (12%) were culture positive for Trichomonas vaginalis and only three of
      these were wet mount positive. CONCLUSION: The InPouch TV test demonstrated an
      epidemiological important infected male population that was not indicated by wet
      mount microscopy.

PMID- 8566986
TI  - Candidal balano-posthitis: a study of diagnostic methods.
AB  - OBJECTIVES: To compare microscopy with culture for diagnosing candidal
      balanoposthitis and to document which diagnostic methods are used in
      genitourinary medicine clinics in Great Britain. DESIGN: (a) Penile material for
      microscopy and fungal culture were obtained from men with balano-posthitis. A
      "plain-slide" method of collecting material for microscopy was compared with a
      novel "adhesive-tape" method of sampling. (b) Questionnaires were sent to all
      genitourinary medicine clinics in Great Britain. SETTING: The Department of
      Genitourinary Medicine, Addenbrooke's Hospital, Cambridge, England. MAIN OUTCOME
      MEASURES: The sensitivity and specificity of microscopy using culture as the
      "gold standard" for diagnosis. RESULTS: Candida was isolated from 35% of 450 men
      with balano-posthitis attending the clinic over a three year period. The
      sensitivity of microscopy compared with culture was 12% ("plain-slide" method of
      material collection) and 65% ("adhesive-tape" method) (p < 0.0001). The
      respective specificities were 95% and 81%. The positive predictive values for the
      two methods of material collection were 50% ("plain-slide" method) and 75%
      ("adhesive-tape" method). The respective negative predictive values were 71% and
      72%. 60% of 250 genitourinary medicine clinics returned questionnaires. 13%
      routinely diagnosed candidal balanoposthitis by appearance only and 34% sometimes
      relied only on clinical appearance. Culture was used by 78% and microscopy by 69%
      of clinics. Material for microscopy was most commonly collected by using a cotton
      wool tipped swab and the Gram stain was the favoured method for microscopy.
      CONCLUSION: Candida is a common cause of balano-posthitis. Diagnosis by
      microscopy has a low sensitivity and varies with the method used for collecting
      material. Although up to one third of genitourinary medicine clinics may rely
      solely on clinical appearance for diagnosis most continue to use microscopy and
      culture.

PMID- 8566987
TI  - Genital porokeratosis of Mibelli.
AB  - Porokeratosis of Mibelli is a disorder of epidermal proliferation in which many
      different clinical forms can be distinguished. Two male patients with a localized
      type of porokeratosis limited to the genitalia are reported. Later in life they
      developed an annular skin lesion with peripheral keratotic ridge. The
      histological examination of a biopsy specimen showed the characteristic features
      of porokeratosis. There was no family history of similar skin disorders and the
      patients were not on any drugs. Genital porokeratosis is probably underdiagnosed
      and we believe that these patients should be followed up on account of the
      precancerous potential of this disease.

PMID- 8566988
TI  - Ciprofloxacin resistant Neisseria gonorrhoeae.

PMID- 8566989
TI  - Prevalence of antibodies to HIV-1 and HIV-2 in women attending a sexually
      transmitted disease clinic in Luanda, Angola.

PMID- 8566990
TI  - Anaphylaxis due to liposomal amphotericin (AmBisome)

PMID- 8566991
TI  - Pre-treatment with hydration and electrolytes may prevent dose limiting
      toxicities during foscarnet induction therapy.

PMID- 8566992
TI  - Chlamydia in women: the more you look, the more you find.

PMID- 8566993
TI  - Syndromic management of genital ulcer disease.

PMID- 8566994
TI  - Ignored trichomonal infestation diagnosed by Papanicolaou smear.

PMID- 8566995
TI  - Polypoidal and giant molluscum contagiosum.

PMID- 8566996
TI  - The value of colposcopy in genitourinary medicine.

PMID- 8566997
TI  - Musical versus visual graphs: cross-modal equivalence in perception of time
      series data.
AB  - By applying multidimensional scaling procedures and other quantitative analyses
      to perceptual dissimilarity judgments, we compared the perceptual structure of
      visual line graphs depicting simulated time series data with that of auditory
      displays (musical graphs) presenting the same data. Highly similar and meaningful
      perceptual structures were demonstrated for both auditory and visual modalities,
      showing that important data characteristics (function slope, shape, and level)
      were perceptually salient in either presentation mode. Auditory graphics may be a
      highly useful alternative to traditional visual graphics for a variety of data
      presentation applications.

PMID- 8566998
TI  - Effects of back support on intra-abdominal pressure and lumbar kinetics during
      heavy lifting.
AB  - Lumbosacral supports (LSSs) have been used to minimize the risk of lower back
      injuries. Theoretically, an LSS will raise intra-abdominal pressure (IAP) and
      reduce loads in the lower back region. This investigation compared three
      different LSSs with an unsupported condition. Nine males lifted a weighted box
      four times, once per condition, at 90% of their one-repetition maximum.
      Conditions were compared in terms of effects on IAP and its relieving force on L5
      S1 kinetics. A multivariate analysis of covariance revealed no statistically
      significant differences among the three LSSs and the nonsupport conditions on the
      aforementioned dependent variables. This suggests that there is no difference
      among LSSs in terms of their biomechanical effects on the lower back region and
      that the use of any LSS does not necessarily afford more protection than a proper
      lift without one.

PMID- 8566999
TI  - Predictors of hearing protection use among workers: implications for training
      programs.
AB  - In this study, we used the conceptual Health Promotion Model to identify
      predictors of hearing protection use among blue-collar workers (N = 504). The
      strongest predictors were self-efficacy, benefits, value, and barriers. Items in
      the barriers scale were most strongly correlated with use and had the greatest
      potential for change. Therefore, items from this scale are being used as the
      primary basis for development of a training intervention program.

PMID- 8567000
TI  - An efficient approach to ARMA modeling of biological systems with multiple inputs
      and delays.
AB  - This paper presents a new approach to AutoRegressive Moving Average (ARMA or ARX)
      modeling which automatically seeks the best model order to represent investigated
      linear, time invariant systems using their input/output data. The algorithm seeks
      the ARMA parameterization which accounts for variability in the output of the
      system due to input activity and contains the fewest number of parameters
      required to do so. The unique characteristics of the proposed system
      identification algorithm are its simplicity and efficiency in handling systems
      with delays and multiple inputs. We present results of applying the algorithm to
      simulated data and experimental biological data In addition, a technique for
      assessing the error associated with the impulse responses calculated from
      estimated ARMA parameterizations is presented. The mapping from ARMA coefficients
      to impulse response estimates is nonlinear, which complicates any effort to
      construct confidence bounds for the obtained impulse responses. Here a method for
      obtaining a linearization of this mapping is derived, which leads to a simple
      procedure to approximate the confidence bounds.

PMID- 8567001
TI  - A comparison of adaptive and nonadaptive filters for reduction of power line
      interference in the ECG.
AB  - We have investigated the relative performance of an adaptive and nonadaptive 60
      Hz notch filter applied to an ECG signal. We evaluated the performance of the two
      implementations with respect to adaptation rate (or transient response time),
      signal distortion, and implementation complexity. We also investigated the
      relative effect of adaptive and nonadaptive 60-Hz filtering on ECG data
      compression. With a 360 Hz sample rate and an adaptation time of approximately
      0.3 s for a 1 mV 60-Hz signal, the adaptive implementation is less complex and
      introduces less noise, particularly in the ST-segment, into a typical ECG signal.
      When applied to ECG signals, prior to data compression by average beat
      subtraction and residual differencing, the residual signal resulting from the
      adaptively filtered signal had an average entropy 0.37 bits per sample (bps)
      lower than the unfiltered signal. The nonadaptive 60-Hz filter produced an
      average entropy decrease of 0.08 bps relative to the unfiltered ECG.

PMID- 8567002
TI  - Screening of vibroarthrographic signals via adaptive segmentation and linear
      prediation modeling.
AB  - This paper proposes a noninvasive method to diagnose chondromalacia patella at
      its early stages by recording knee vibration signals (also known as
      vibroarthrographic or VAG signals) over the mid-patella during normal movement.
      An adaptive segmentation method was developed to segment the nonstationary VAG
      signals. The least squares modeling method was used to reduce the number of data
      samples to a few model parameters. Model parameters along with a few clinical
      parameters and a signal variability parameter were then used as discriminant
      features for screening VAG signals by applying logistic and discriminant
      algorithms. The system was trained using ten normal and eight abnormal signals.
      It correctly screened a separate test set of ten normal and eight abnormal
      signals except for one normal signal. The proposed method should find use as an
      alternative technique for diagnosis of knee joint pathology or as a test before
      arthroscopy or major knee surgery.

PMID- 8567003
TI  - A cross-coupling model of vertical vergence adaptation.
AB  - Vertical disparity vergence aligns the two eyes in response to vertical
      misalignment (disparity) of the two ocular images. An adaptive response to
      vertical disparity vergence is demonstrated by the continuation of vertical
      vergence when one eye is occluded. The adaptive response is quantified by
      vertical phoria, the eye alignment error during monocular viewing. Vertical
      phoria can be differentially adapted to vertical disparities of opposite sign
      located at two positions along the horizontal or vertical head-referenced axes.
      Vertical phoria aftereffects vary in amplitude as the eyes move from one adapted
      direction of gaze to another along the adaptation axis. A cross-coupling model
      was developed to account for the spatial variations of vertical phoria
      aftereffects. The model is constrained according to both single cell recordings
      of eye position sensitive neurons, and eye position measurements during and
      following adaptation. The vertical phoria is computed by scaling the activities
      of eye position sensitive neurons and converting the scaled activities into a
      vertical vergence signal. The three components of the model are: neural
      activities associated with conjugate eye position, cross-coupling weights to
      scale the activities, and vertical vergence transducers to convert the weighted
      activities to vertical vergence. The model provides a biologically plausible
      mechanism for vertical vergence adaptation.

PMID- 8567004
TI  - A noninvasive technique for detecting hypernasal speech using a nonlinear
      operator.
AB  - Speakers with a defective velopharyngeal mechanism produce speech with
      inappropriate nasal resonance (hypernasal speech). It is of clinical interest to
      detect hypernasality as it is indicative of an anatomical, neurological, or
      peripheral nervous system problem. There are various clinical techniques used to
      determine hypernasality. The current techniques are physically invasive or
      intrusive to some extent. A preferred approach for detecting hypernasality, would
      be noninvasive to maximize patient comfort and naturalness of speaking. In this
      study, a noninvasive technique based on the Teager Energy operator is proposed.
      Utilizing a property of the Teager Energy operator and a model for normal and
      nasalized speech, a significant difference between the Teager Energy profile for
      lowpass and bandpass filtered nasalized speech is shown. This difference is shown
      to be nonexistent for normal speech. A classification algorithm is formulated
      that detects the presence of hypernasality using a measure of the difference in
      the Teager Energy profiles. The classification algorithm was evaluated using a
      native English speaker population producing front (/i/) and mid (/A/) vowels.
      Results show that the presence of hypernasality in speech can be reliably
      detected using the proposed classification algorithm.

PMID- 8567005
TI  - Estimation of the power spectral density in nonstationary cardiovascular time
      series: assessing the role of the time-frequency representations (TFR).
AB  - Spectral analysis of cardiovascular series has been proposed as a noninvasive
      tool for investigating the autonomic control of the cardiovascular system. The
      analysis of such series during autonomic tests requires high resolution
      estimators that are capable to track the transients of the tests. A comparative
      evaluation has been made among classical (FFT based), autoregressive (both block
      and sequential mode) and time-frequency representation (TFR) based power spectral
      estimators. The evaluation has been performed on artificial data that have
      typical patterns of the nonstationary series. The results documented the
      superiority of the TFR approach when a sharp time resolution is required.
      Moreover, the test on a RR-like series has shown that the smoothing operation is
      effective for rejecting TFR cross-terms when a simple, two-three components
      series is concerned. Finally, the preliminary application of the selected methods
      to real RR interval time series obtained during some autonomic tests has shown
      that the TFR are capable to correctly represent the transient of the series in
      the joint time-frequency domain.

PMID- 8567006
TI  - Maximum likelihood analysis of cardiac late potentials.
AB  - This study presents a new time-domain method for the detection of late potentials
      in individual leads. Basic statistical properties of the ECG samples are modeled
      in order to estimate the amplitude and duration of late potentials. The signal
      model accounts for correlation in both time and across the ensemble of beats.
      Late potentials are modeled as a colored process with unknown amplitude which is
      disturbed by white, Gaussian noise. Maximum likelihood estimation is applied to
      the model for estimating the amplitude of the late potentials. The resulting
      estimator consists of an eigenvector-based filter followed by a nonlinear
      operation. The performance of the maximum likelihood procedure was compared to
      that obtained by traditional time-domain analysis based on the vector magnitude.
      It was found that the new technique yielded a substantial improvement of the
      signal-to-noise ratio in the function used for endpoint determination. This
      improvement leads to a prolongation of the filtered QRS duration in cases with
      late potentials.

PMID- 8567007
TI  - Estimating defibrillation efficacy using combined upper limit of vulnerability
      and defibrillation testing.
AB  - It is frequently necessary, both clinically and in the laboratory, to estimate
      how strong a stimulus is required to defibrillate. Current techniques for forming
      such estimates require the repeated induction of ventricular fibrillation (VF)
      and subsequent attempts at defibrillation (DF testing). DF testing can be time
      consuming and in the operating room may increase the patient risks. A novel
      scheme is presented which combines DF testing with upper limit of vulnerability
      (ULV) testing. ULV testing is a relatively safe procedure which yields data well
      correlated with defibrillation efficacy. A Bayesian statistical model of combined
      ULV/DF testing is presented which is both powerful and concise. The model is used
      in two examples to design minimum rms error protocols and estimators for the DF95
      (the stimulus strength which defibrillates 95% of the time). A simulation for
      humans of one example solution shows that a single VF episode of combined ULV/DF
      testing (rms error = 23% of the mean DF95) is better than two VF episodes with DF
      testing alone (25%). The simulation results for a second example are directly
      compared with laboratory results from six pigs, showing a less than 1.0% average
      difference between the simulated and measured rms errors.

PMID- 8567008
TI  - Finite element analysis of temperature controlled coagulation in laser irradiated
      tissue.
AB  - The Theoretical study of thermal damage processes in laser irradiated tissue
      provides further insight into the design of optimal coagulation procedures.
      Controlled laser coagulation of tissue was studied theoretically using a finite
      element method with a modulating laser heat source to simulate feedback
      controlled laser delivery with a constant surface temperature. The effects of
      uncertainty in scattering and absorption properties of the tissue, thermal
      denaturation induced changes in optical properties, and surface convection were
      analyzed. Compared to a single pulse CW irradiation in which a doctor would
      presumably stop CW laser delivery after noticing some effect such as vaporization
      or carbonization, the constant surface temperature scenario provided a better
      overall control over the coagulation process. In particular, prediction of
      coagulative damage in a constant temperature scenario was less sensitive to
      uncertainties in optical properties and their dynamic changes during the course
      of coagulation. Also, subsurface overheating under surface convective conditions
      could be compensated for under constant temperature irradiation by lowering the
      surface temperature.

PMID- 8567009
TI  - Spatial distribution of high-frequency electromagnetic energy in human head
      during MRI: numerical results and measurements.
AB  - Finite Element Method (FEM) using 26-node isoparametric finite elements was
      applied for modeling saddle-shaped head coils used in Magnetic Resonance Imaging
      (MRI) generating linearly polarized radiofrequency (RF) pulses at 64 MHz. The
      human head was modeled from MR scans of a volunteer and additional information
      were taken from Atlas of Sectional Human Anatomy. The physical dimensions of the
      head coil and the head permit a calculation of the outside magnetic field by a
      quasistatic approach. Of course, a full-wave approach was applied within the
      head. Values of specific energy--specific absorption (SA)--as well as of specific
      power--specific absorption rate (SAR)--were calculated by the method, simulating
      the real exposure conditions during MRI. Although the results of the used
      numerical method were compared previously to the results of the analytical
      solution with homogeneous sphere and to the results of RF measurements on
      heterogeneous phantom, a comparison between the numerical results of the modeled
      human head and in vivo measurements performed on the human head of the volunteer
      was made once more. Since the results are in excellent agreement, they argue for
      the correctness of the numerical method. The "worst-case" temperature elevations
      delta theta of the "hot-spots" were calculated, as well. Finally, the results of
      SA, SAR, and delta theta are compared to the existing recommendations.

PMID- 8567010
TI  - On the contribution of volume currents to the total magnetic field resulting from
      the heart excitation process: a simulation study.
AB  - Data from a simulation study of volume current contribution to the total magnetic
      field produced in the heart excitation process is presented. Contributions from
      different tissue types are analyzed and effects of torso size are studied. A high
      resolution finite element model of an adult male torso composed of 19 tissue
      types is used. It has detailed description of tissue geometries and therefore is
      well suited for analyzing the contribution of the primary and secondary currents
      to the magnetic field. The computed results show major contribution of volume
      currents from blood, myocardium, and lungs and less significant contribution from
      liver, muscle, and other tissues. The contribution to the volume currents from
      the blood in the ventricles was highest. These simulations suggest that
      contribution to the total magnetic field due to volume currents flowing in
      tissues other than blood could be accounted for by simply multiplying the total
      field values by a constant. Values of these multipliers would be based on the
      tissue type and time in the excitation cycle. Effects of torso size on the
      computed magnetic fields are also evaluated. Our data shows that a torso
      extending approximately 3 cm above and below the heart produces field patterns
      similar to a larger torso model extending from top of guts to the bottom of neck.
      Thus a shorter torso model would be sufficient for cardiac magnetic field
      analysis. These results are of interest for future modeling of magnetocardiograms
      and solving the inverse problem.

PMID- 8567011
TI  - High levels of protection induced by a 40-mer synthetic peptide vaccine against
      the intestinal nematode parasite Trichinella spiralis.
AB  - Parenteral vaccination, using a 40-mer synthetic peptide from a 43,000 MW
      immunodominant glycoprotein secreted by the intestinal nematode parasite
      Trichinella spiralis, induced high levels of protection against a subsequent
      challenge infection in mice. The expulsion of adult worms from the gut was
      accelerated following vaccination with peptide 40-80, but peptides 81-120 and 121
      160 were not protective. Mesenteric lymph node cells taken from T. spiralis
      infected mice showed some proliferation in response to in vitro stimulation with
      peptide 40-80, but were unaffected by peptide 81-120. As expulsion of T. spiralis
      is known to be brought about by T-cell-mediated inflammatory events in the
      intestine, the ability of the 40-80 sequence to promote accelerated worm
      expulsion upon challenge infection may reflect induction of a specific and
      appropriate T-cell response. To our knowledge, this is the first report of a
      protective synthetic peptide vaccine against an intestinal nematode.

PMID- 8567012
TI  - Unimpaired clearance of Mycobacterium bovis BCG infection in selectively T-cell
      anergic TCR-V beta 8.2 transgenic mice.
AB  - The anergy induced in mice with staphylococcal enterotoxin B (SEB) has been shown
      to involve selective unresponsiveness in cytokine expression. While interleukin-2
      (IL-2), IL-3 and IL-4 mRNA levels are substantially reduced in anergic T cells
      upon restimulation with SEB, mRNA for interferon-gamma (IFN-gamma) is expressed
      normally. On the other hand, infection with Nippostrongylus brasiliensis is known
      to break an established T-cell anergy. This knowledge prompted us to examine the
      effect of infection with an intracellular microbe, bacillus Calmett-Guerin (BCG),
      on the expression of anergy induced with SEB. We have demonstrated that while the
      SEB-induced anergy was not abrogated by BCG infection, the V beta 8.2 transgenic
      mice, in which almost all T cells were anergized with SEB, were capable of
      developing the effective acquired protective immunity, possibly through the
      preserved capacity to induce IFN-gamma leading to induction of nitric oxide
      synthase.

PMID- 8567013
TI  - T-cell lung granulomas induced by sepharose-coupled Mycobacterium tuberculosis
      protein antigens: immunosuppressive phenomena reversed with cyclophosphamide and
      indomethacin.
AB  - We induced lung granulomas in BALB/c mice by intratracheal instillation of
      Sepharose beads coated with a Mycobacterium tuberculosis protein extract.
      Granulomas composed of macrophages and lymphocytes were induced. The
      granulomatous reaction reached its peak 3-7 days after challenge and lasted for
      approximately 1 month. Immunolabelling of tissue sections and bronchial washings
      revealed that granulomas were predominantly composed of T lymphocytes with the
      cytotoxic-suppressor phenotype (CD8+). Granulomas were associated with a
      significant decrease in anti-mycobacterial immunity manifested by a drop in
      delayed-type hypersensitivity reactions and antibody titres. The
      immunosuppressive phenomena were abolished with cyclophosphamide or indomethacin.
      Control granulomas induced with methylated bovine serum albumin (BSA) were
      smaller and composed by similar numbers of CD4+ and CD8+ cells. BSA granulomas
      did not alter antibody titres but they decreased delayed-type hypersensitivity to
      BSA which was restored to normal with indomethacin but not with cyclophosphamide.
      Our findings show that mycobacterial proteins anchored to Sepharose beads are
      granulomatogenic and that they preferentially recruit CD8+ cells which, together
      with locally produced prostaglandins, down-modulate cell-mediated and humoral
      immunity to mycobacterial antigens.

PMID- 8567014
TI  - Sequential production of Th1 and Th2 cytokines in response to live bacillus
      Calmette-Guerin.
AB  - Causes of individual variation in susceptibility to mycobacterial diseases are
      only partly understood. An efficient cell-mediated immune response is crucial for
      resistance. Macrophages and T cells interact to eliminate the mycobacteria,
      partially through the effects of secreted cytokines. A vigorous anti-bacterial
      inflammatory response is sometimes accompanied by severe tissue damage, while
      immunosuppression leads to progressive infection. Here, live, attenuated
      Mycobacterium bovis, bacillus Calmette-Guerin (BCG), was used as a model antigen
      to study cytokine production at the single-cell level in response to
      mycobacteria. Peripheral blood mononuclear cells from healthy individuals were
      challenged in vitro and the kinetics and frequencies of cytokine-producing cells
      were studied by immunofluorescent visualization of intracellular cytokines.
      Fourteen cytokines were assayed; interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL
      1 receptor antagonist (IL-1ra), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10,
      interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), TNF-beta
      and granulocyte-macrophage colony-stimulating factor (GM-CSF). A sequential
      production of T helper-1 (Th1) and T helper-2 (Th2) cytokines was induced by BCG.
      Early, at days 1-2 after stimulation, the response was dominated by monokines and
      a low IFN-gamma and TNF-beta production. At days 4-5 there was a marked
      production of Th1 lymphokines, with approximately 6% IFN-gamma+ cells, 4% TNF
      beta+ cells and 2% IL-2+ cells. Late in the reaction, at days 10-12, a Th2
      response with IL-4, IL-5 and IL-10 was detected, while the synthesis of Th1
      lymphokines and monokines declined. Overall, our results provide further evidence
      of IFN-gamma as the major cytokine induced by mycobacteria in healthy
      individuals, but also suggest that Th2 cytokines participate in the response.

PMID- 8567015
TI  - Protection against tuberculosis by bone marrow cells expressing mycobacterial
      hsp65.
AB  - Although mice acquire only a slight degree of protection against tuberculosis by
      immunization with Mycobacterium leprae (M. leprae) hsp65 in incomplete Freund's
      adjuvant, protection is substantial following immunization by injection with J774
      macrophage-like tumour cells that express the protein from the mycobacterial gene
      via a retroviral vector. We here took the same vector, used it to transfect the
      gene into normal murine bone marrow cells in vitro, and then used the transfected
      cells to reconstitute haematopoiesis in lethally irradiated mice. Bone marrow
      cell clonal expansion and production of the protein in vivo resulted in specific
      delayed-type hypersensitivity and protection against challenge with Mycobacterium
      tuberculosis (M. tuberculosis) in about half of recipients. Counts of live
      bacteria in liver at 3 weeks were fivefold lower in delayed-type hypersensitivity
      (DTH)-positive than in DTH-negative mice. Other mice acquired neither DTH nor
      protection despite the presence of the protein in peripheral blood.

PMID- 8567016
TI  - Occult expression of CD32 (Fc gamma RII) in normal human peripheral blood
      mononuclear cells.
AB  - Three main classes of Fc gamma receptor (Fc gamma R) have been described on the
      surface of normal human peripheral blood peripheral blood mononuclear cells.
      These receptors are thought to play an important role in many immune mechanisms.
      Following interaction with ligand, i.e. IgG in the form of an immune complex,
      receptor cross-linking occurs and some isoforms of Fc gamma R become internalized
      and will recycle back to the cell surface. This mechanism may be important in
      signal transduction pathways. In this study we have shown that a particular type
      of Fc gamma R (CD32), which is normally expressed on the surface of B cells, can
      be detected by flow-cytometry within the cytoplasm of up to 90% of normal human
      peripheral blood lymphocytes. The function of this 'occult' CD32 is not known but
      may represent an internal receptor pool that is up-regulated following cell
      activation.

PMID- 8567017
TI  - Age-related defects in CD2 receptor-induced activation in human T-cell subsets.
AB  - It is well documented that the proliferative capacity of T cells declines with
      advancing age. There are, however, conflicting data as to the role of the
      accessory cell and whether or not this loss in responsiveness extends to all T
      cell stimuli and to all T cells. We report here on the capacity of subpopulations
      of peripheral blood CD4+ T cells from the healthy aged to proliferate in response
      to anti-CD2 receptor-induced activation in the complete absence of accessory
      cells by using various exogenous cofactors as second signals. These costimulatory
      factors included phorbol 12-myristate 13-acetate (PMA), interleukin (IL)-1, IL-2,
      IL-6 and IL-7 and the monoclonal antibodies, anti-CD28 and anti-CD44. Under these
      conditions, the proliferative responsiveness of CD4+CD45RO+ T cells from the aged
      was found to be comparable to young control cells for all stimuli tested, except
      anti-CD2 plus IL-7. This suggests that signal transduction pathways involving
      CD2, except IL-7-mediated events, are essentially intact in 'old' memory CD4+ T
      cells. On the other hand, several cofactors, namely IL-2, IL-6, IL-7 and to a
      lesser extent IL-1 beta and PMA, failed to support adequately CD2-induced
      activation in 'old' CD4+CD45RA+ T cells suggesting severe and multiple signalling
      deficiencies in this subset.

PMID- 8567018
TI  - CD45RO expression on bovine T cells: relation to biological function.
AB  - The 180,000 MW isoform of CD45 (CD45RO) has been identified in cattle with a
      novel monoclonal antibody (mAb) (IL-A116). This has allowed a more precise
      analysis of T-cell function in relation to CD45 isoform expression. Within the
      CD4+ and CD8+ T-cell populations, CD45RO+ and CD45RO- subsets were evident. Most
      CD4+ and CD8+ T cells that expressed the CD45RO isoform did not express the
      220,000 and 205,000 MW isoforms recognized by mAb CC76. In contrast, the WC1+,
      CD2-, CD4-, CD8-, gamma delta T-cell receptor (TCR)+ T cells in bovine peripheral
      blood mononuclear cells (PBMC) were all CD45RO+. Monocytes and granulocytes were
      CD45RO+ but B cells were CD45RO-. Sorting experiments with CD4+ T cells from an
      immunized calf demonstrated that proliferative responses to ovalbumin (OVA) were
      entirely within the CD45RO+ subset. Following stimulation with concanavalin A
      (Con A) the CD45RO- subset of CD4+ T cells produced transcripts for interleukin-2
      (IL-2) but not IL-4 or interferon-gamma (IFN-gamma), while the CD45RO+ subset
      produced mRNA for IL-2, IL-4 and IFN-gamma. Biologically active IL-2 was present
      in supernatants from both CD45RO+ and CD45RO-, CD4+ T cells, and IFN-gamma
      protein was identified by ELISA in supernatants from the CD45RO+ subset,
      confirming the production of cytokines implied by polymerase chain reaction
      (PCR). In contrast, sorting experiments with CD8+ T cells from animals immune to
      the protozoan parasite Theileria parva revealed substantial numbers of cytotoxic
      T-lymphocyte precursors in both the CD45RO+ and CD45RO- subsets. Thus it appears
      that although all antigenically primed CD4+ T cells remain CD45RO+, and
      expression of this molecule consequently identifies memory cells within PBMC,
      antigenically primed CD8+ T cells down-regulate CD45RO expression after
      activation.

PMID- 8567019
TI  - Differential cytokine production following chronic exposure of mice to chemical
      respiratory and contact allergens.
AB  - It has been demonstrated previously that a selective pattern of mitogen-inducible
      interleukin-4 (IL-4) production becomes apparent in mice after temporal evolution
      of the immune response to different classes of chemical allergen. Mitogen
      stimulated draining lymph node cells (LNC) isolated after primary exposure to
      both the respiratory allergen trimellitic anhydride (TMA) and oxazolone, a
      contact allergen, secreted similar amounts of IL-4. Following secondary exposure,
      however, TMA, but not oxazolone, caused a marked increase in IL-4 production,
      consistent with the stimulation by TMA of a T-helper type-2 (Th2)-type response.
      In the present study, cytokine production characteristic of Th1 (interferon
      gamma; IFN-gamma) and Th2 (IL-4 and IL-10) cell activation was examined following
      chronic exposure of mice to allergen over a 13-day period. In accord with
      previous studies, chronic exposure to TMA, but not to oxazolone, resulted in a
      substantial potentiation of mitogen-inducible IL-4 secretion. In addition,
      spontaneous IL-10 production by TMA-activated LNC was significantly higher than
      by cells prepared from oxazolone-exposed animals. The lower levels of Il-4 and IL
      10 elaborated by oxazolone-activated LNC were not attributable to a reduced
      potential to secrete cytokine per se, as significantly more IFN-gamma was
      produced compared with TMA-activated LNC. It is proposed that these divergent
      cytokine production patterns reflect the selective stimulation of Th1- and Th2
      type responses by contact and respiratory chemical allergens.

PMID- 8567020
TI  - The 5' coding sequence of IL-2 receptor alpha chain mRNA mediates mRNA
      stabilization by HTLV-1 Rex.
AB  - The interleukin-2 receptor alpha chain (IL-2R alpha) is a T-cell growth factor
      receptor and is known to be induced in helper T cells by infection with human T
      cell leukaemia virus type-1 (HTLV-1). The Rex protein of HTLV-1 has been shown to
      stabilize IL-2R alpha mRNA. Although the 3' untranslated region of many RNA has
      been regarded as a key element for stabilization, we found that the first 300
      bases of the IL-2R alpha protein coding sequence were necessary for stabilization
      of the mRNA. As the first 201 bases were not sufficient for this effect, we
      conclude that the bases at position 201-300 downstream of the AUG start are
      important for stabilization.

PMID- 8567021
TI  - IgA subclasses in HIV disease: dichotomy between raised levels in serum and
      decreased secretion rates in saliva.
AB  - This study sought to determine IgA, IgA1 and IgA2 concentrations and secretion
      rates in unstimulated whole saliva and stimulated parotid saliva and IgA, IgA1
      and IgA2 concentrations in serum from asymptomatic human immunodeficiency virus
      (HIV)-infected, acquired immune deficiency syndrome (AIDS) and control subjects.
      In whole and parotid saliva the mean IgA, IgA1 and IgA2 concentrations in the HIV
      and AIDS groups were lower than the control group (P < 0.05). Unstimulated whole
      and stimulated parotid saliva flow rates were lower in the HIV and AIDS groups
      compared with the control group, and reached statistical significance with
      respect to the mean parotid saliva flow rate in the AIDS group (P < 0.05). Mean
      IgA, IgA1 and IgA2 secretion rates in both the HIV and AIDS groups were
      significantly less than the controls (P < 0.05). In contrast, serum IgA, IgA1 and
      IgA2 concentrations were markedly raised in the HIV and AIDS groups compared with
      the control group (P < 0.001). There was no correlation between saliva and serum
      IgA concentrations within individuals. This study suggests that, in spite of the
      raised, polyclonally activated serum IgA concentrations associated with HIV
      infection, salivary IgA concentrations and secretion rates are reduced,
      emphasizing the dichotomy between systemic and secretory immunity.

PMID- 8567022
TI  - Tissue-associated phenotypic heterogeneity of peripheral B cells in mice.
AB  - After their primary differentiation and selection in the bone marrow, the cells
      of B lineage are distributed to the peripheral lymphoid system. Here we report
      that, with the use of a novel rat monoclonal antibody (IBL-2), a tissue-related
      phenotypic difference could be observed in the peripheral B-cell compartment in
      mouse. The antigen recognized by this antibody is a 25,000/29,000 MW
      heterodimeric cell surface molecule which is resistant to phosphatidylinositol
      phospholipase C treatment, but is sensitive to proteases. The antigen was found
      to be expressed by the majority of B cells from the spleen, whereas the B cells
      from other peripheral sources (lymph nodes and Peyer's patches) proved to be
      negative. The staining pattern of splenic B cells was heterogeneous, containing a
      substantial dim population (IBL-2lo), and a smaller, intensely stained fraction
      (IBL-2hi) within the positive subset. Unlike the B cells, the T cells were
      negative in every peripheral lymphoid tissue analysed. In addition, the ratios
      between the various IBL-2-reactive B cells (positive to negative and, within the
      positive population, the IBL-2lo to IBL-2hi, respectively) in the spleen were
      quite similar to that of B cells in the bone marrow. Furthermore, the levels of L
      selectin expressed by the various IBL-2-reactive subpopulations were found to be
      heterogeneous both in the bone marrow and in the spleen. The bone marrow cells
      could be resolved into double negative, L-selectin +/-/IBL-2lo, L-selectin--IBL
      2lo, and L-selectin-/IBL-2hi populations, respectively. In the spleen, an
      additional fraction with L-selectin+/IBL-2- phenotype could be detected. In both
      tissues, the overwhelming majority of IBL-2hi cells were found at the MEL-14-
      compartment. We conclude that either these findings may reflect a heterogeneous
      development state within the peripheral B-cell pool, with a substantial fraction
      of splenic B cells being less differentiated than those in other peripheral
      lymphoid tissues, or alternatively, the differential reactivity of murine B cells
      with the IBL-2 monoclonal antibody is due to their tissue location.

PMID- 8567023
TI  - Hexachlorobenzene treatment increases the number of splenic B-1-like cells and
      serum autoantibody levels in the rat.
AB  - In the present study, the role of B-1 cells in hexachlorobenzene (HCB)-induced
      autoimmune aberrations in the Wistar rat was investigated. To that end, male and
      female rats were exposed to a semi-synthetic diet containing 0 or 1000 mg HCB/kg
      food for 3 weeks. After dissection, serum was prepared form coagulated blood to
      determine (auto)antibody levels, and spleens and lymph nodes were isolated and
      weighed. Cell suspensions were prepared, counted and analysed for B- and T-cell
      subsets by flow cytometry. Quantification of antibody-secreting cells (ASC) in
      spleen cell suspensions was done with an ELISPOT assay. Previous findings that
      HCB treatment induced an increase of relative lymph node and spleen weights and
      serum (auto)antibody levels were confirmed, while it appeared that numbers of
      some lymph nodal, and of the splenic large cell populations, were elevated as
      well. HCB treatment did not change subsets of lymph nodal T and B cells, but
      elevated the absolute numbers of large splenic CD4+ T cells by about 70%,
      IgMdull/IgDbright B cells by about 60%, and IgMbright/IgDdull B cells by about
      200% cells of control numbers, and the absolute numbers of splenic IgM and IgG
      (auto) ASC by 300-400% of the control numbers. As splenic IgMbright/IgDdull
      numbers and ASC numbers correlated with statistical significance, the results
      indicate that HCB treatment selectively activates rat splenic B-1 cells, which
      may underlie the elevation of serum autoantibody levels.

PMID- 8567024
TI  - C3, C4, factor B and HLA-DR alpha mRNA expression in renal biopsy specimens from
      patients with IgA nephropathy.
AB  - The deposition of complement in the kidney mesangium is a constant finding
      associated with renal injury in IgA nephropathy, even though IgA does not bind
      complement. We have previously reported that complement gene expression in the
      kidney increases concurrently with the progression of immune complex disease in
      murine lupus nephritis. We have now studied the expression of C3, C4, factor B
      and HLA-DR alpha mRNA by in situ hybridization in renal biopsy specimens of
      patients with IgA nephropathy and compared these findings to those in patients
      with other immune-mediated diseases of the kidney, hereditary nephritis and
      normal kidney. In IgA nephropathy, C3 and factor B mRNA were expressed in the
      renal tubular epithelial cells, while no expression of either C3 or factor B mRNA
      was apparent in the glomerulus. Specimens from patients with other immune
      mediated forms of chronic glomerulonephritis also showed a similar pattern of
      expression of C3 and factor B mRNA only in the tubules, but not in the
      glomerules. However, C3 and factor B mRNA were not found in normal kidney tissue
      or biopsy specimens from patients with hereditary nephritis. C4 mRNA was
      expressed in the tubular epithelial cells in all specimens examined, indicating
      that C4 mRNA is constitutively expressed in the human kidney. In IgA nephropathy
      HLA-DR alpha mRNA was observed in the interstitium, but not the tubules or
      glomerular cells. In contrast, HLA-DR alpha mRNA was present in the glomerulus
      and scattered in the interstitium in other immune-mediated kidney diseases. There
      was no expression of HLA-DR alpha mRNA in hereditary nephritis or normal kidney.
      Our findings, which reflect the immunopathogenic events in vivo, provide new
      insights as to the interpretation of the molecular immunology of this immune
      complex disease.

PMID- 8567025
TI  - Chondrocyte-peripheral blood mononuclear cell interactions: the role of ICAM-1.
AB  - Chondrocytes express a number of cell-surface molecules that mediate cell-cell or
      cell-matrix interactions. The expression of intercellular adhesion molecule-1
      (ICAM-1) by chondrocytes under inflammatory conditions has been well documented.
      Here we demonstrate the involvement of ICAM-1-, CD18- and RGD-dependent adhesion
      mechanisms in chondrocyte-T-cell adhesion and in cell-mediated killing of
      chondrocytes in vitro. In the absence of cytokine stimulation, chondrocyte
      peripheral blood mononuclear cell (PBMC) interactions were unaffected by
      inhibition of ICAM-1-dependent pathways but were significantly reduced by
      blockade of CD18- and RGD-dependent pathways. Following cytokine stimulation
      chondrocyte-PBMC adhesion and chondrocyte killing were significantly increased.
      These effects could be inhibited by the blockade of ICAM-1.

PMID- 8567026
TI  - Restricted expression of galactose/N-acetylgalactosamine-specific macrophage C
      type lectin to connective tissue and to metastatic lesions in mouse lung.
AB  - We investigated expression of macrophage galactose/N-acetylgalactosamine-specific
      C-type lectin (MMGL) in normal mouse lung tissue and in lungs with metastatic
      nodules produced by OV2944-HM-1 mouse metastatic ovarian tumour cells. Cells
      expressing MMGL were detected in tissue sections using a rat monoclonal antibody
      (mAB) specific for MMGL, mAb LOM-14. The regions containing cells immunostained
      using mAb LOM-14 were restricted to the connective tissue surrounding blood
      vessels and respiratory epithelia, whereas alveolar regions of lung parenchyma
      were essentially devoid of these cells. In contrast, a significant number of
      cells in the alveolar regions was shown to express Mac-1 antigen (CD11b/CD18) and
      leucocyte common antigen (CD45). Immunoelectron microscopic study revealed the
      presence of MMGL in the intracellular vesicles of cells residing in connective
      tissue. In the tumour-bearing mice, MMGL-positive cells were also present within
      metastatic nodules. Their localization outside of the nodules was restricted to
      connective tissue. Cells with Mac-1 antigens were seen both in the nodules and in
      the alveolar regions. These results indicate that MMGL serves as a unique
      macrophage marker in mouse lung tissue due to its topographical site-dependent
      pattern of expression. The present results also suggest a possible involvement of
      macrophages expressing MMGL in the immune response directed against metastatic
      tumour cells.

PMID- 8567027
TI  - Monocytes control gamma/delta T-cell responses by a secreted product.
AB  - Gamma-irradiated ex vivo bovine monocytes induce proliferation of gamma/delta T
      cells in the autologous mixed lymphocyte reaction (AMLR), whereas when not
      irradiated they prevent this response. In contrast, non-irradiated autologous
      monocytes have no effect on bovine alpha/beta T-cell proliferation in the
      allogenic MLR suggesting that the regulation is specific for gamma/delta T-cell
      responses. Here, we showed that the inhibition was not mediated by inducing cell
      death and that the ability of ex vivo monocytes to prevent proliferation of
      gamma/delta T cells was not generalized in that gamma/delta T cells still
      responded to mitogenic stimulation. Inhibition of the AMLR by non-irradiated
      monocytes could not be overcome by addition of interleukin-2 to the cultures or
      by costimulation with antibodies to WC1, a gamma/delta T-cell-specific cell
      surface differentiation antigen shown elsewhere by us to be involved in
      activation of gamma/delta T cells. Furthermore, we showed that monocytes
      inhibited gamma/delta T-cell responses via a soluble product since inhibition
      occurred even when monocytes and gamma/delta T cells were separated by membranes
      of transwells or when supernatants from monocyte cultures were added to AMLR
      cultures. Maximal secretion of the inhibitory product by the monocytes occurred
      during the first 6 hr of in vitro culture at 37 degrees, rapidly decreased
      thereafter, and did not occur when monocytes were incubated at 4 degrees. The
      inhibition was not attributable to nitric oxide, reactive oxygen intermediates,
      prostaglandin E2 or transforming growth factor-beta (TGF-beta) but the ability of
      monocyte supernatants to mediate inhibition was sensitive to heating at 65
      degrees. Lipopolysaccharide and granulocyte-macrophage colony-stimulating factor
      activation of monocytes temporarily abrogated their ability to inhibit
      proliferation. In contrast, heat-shocking had no effect on their ability to
      inhibit. We hypothesize that non-irradiated monocytes produce the inhibitory
      material in vivo in order to regulate gamma/delta T-cell responses to self
      derived monocyte membrane components, but that when monocytes are altered by
      infection, transformation, irradiation, or cytokine activation, production of the
      inhibitor is temporarily suspended allowing stimulation of gamma/delta T cells to
      occur.

PMID- 8567028
TI  - Major histocompatibility complex class I presentation of exogenous and endogenous
      protein-derived peptides by a transfected human monocyte cell line.
AB  - Monocyte/macrophages are professional antigen-presenting cells of the cellular
      immune system, serving to generate peptides for major histocompatibility complex
      (MHC) class II-restricted recognition by CD4+ T-lymphocyte effector cells.
      Antigen presentation by these cells involves the internalization of extracellular
      proteins and their fragmentation within vacuolar compartments. The resulting
      peptides become associated with MHC class II molecules. The final destination of
      exogenous peptide antigens, however, is not absolute in monocytes. Processed
      peptides, derived from exogenous proteins, can also associate with MHC class I
      molecules. To study simultaneous presentation of peptides derived from exogenous
      and endogenous proteins by human leucocyte antigen (HLA) class I molecules, we
      isolated the peptides from a human immunodeficiency virus nef transfected U937
      monocytic cell line. The HLA class I-bound peptides were separated by reverse
      phase-high performance liquid chromatography. Comparison of the peptide sequence
      data with protein databases revealed that the peptides derived from
      extracellular, as well as intracellular, proteins, suggesting that monocytes have
      a more generalized MHC class I antigen-processing pathway than previously
      documented.

PMID- 8567029
TI  - Interleukin-1 and interleukin-6 gene expression in human monocytes stimulated
      with Salmonella typhimurium porins.
AB  - The aim of this study was to verify whether Salmonella typhimurium porins can
      affect the expression of interleukin-1 (IL-1) and interleukin-6 (IL-6) genes.
      Human monocytes were treated with porins, and total RNAs were analysed by
      Northern blotting to evaluate the expression of IL-1 alpha, IL-1 beta and IL-6 in
      both treated and untreated cell cultures. Porins induced a significant increase
      in IL-1 and IL-6 transcripts. This increase was related to the dose of porins,
      and it peaked 5 hr after treatment. The same results were obtained when polymyxin
      B was added to the porin preparation to eliminate eventual traces of
      lipopolysaccharide (LPS) associated with porins. The porins-mediated increase in
      interleukin transcripts did not require de novo protein synthesis, and it was
      because of the enhanced half-life of IL-1 and IL-6 mRNAs, rather an increased
      rate of gene transcription. These data suggest that porins may affect
      inflammatory and immunological responses by enhancing the expression of cytokine
      genes.

PMID- 8567030
TI  - Independent down-regulation of EP2 and EP3 subtypes of the prostaglandin E2
      receptors on U937 human monocytic cells.
AB  - Co-expression of EP2 and EP3 subtypes of prostaglandin E2 (PGE2) receptors (R) by
      U937 human monocytic cells permitted comparative studies of desensitization of
      each subtype. Specific binding of [3H]PGE2 to membranes of U937 cells showed a Kd
      of 2.9 +/- 0.3 nM (mean +/- SEM) and a Bmax of 40.5 +/- 1.0 fmol/mg protein, and
      was competitively inhibited by PGE2 > or = PGE1 > PGF2 alpha > PGD2 > PGI2. EP2 R
      and EP3 R mRNA were detected by reverse transcription-polymerase chain reaction
      and Northern blots. EP3 R expression was demonstrated by inhibition of [3H]PGE2
      binding with the EP1/EP3 agonist sulprostone [50% inhibitory concentration (IC50
      = 3.3 +/- 0.6 nM)] and the EP3/EP2 agonist M&B 28767 (IC50 = 2.1 +/- 0.3 nM), but
      not with the EP1 antagonist SC-19220. EP2 R protein was identified by Western
      blot analysis using specific rabbit IgG antibodies to an amino-terminal peptide
      of the EP2 R. EP2 R transduced PGE2 stimulation of significant increases in
      cellular [cAMP]i [50% effective concentration (EC50 = 20 +/- 2.5 nM)], and EP3 R
      mediated sulprostone inhibition of forskolin elevation of [cAMP]i (IC50 = 1.3 +/-
      0.4 nM). Pretreatment of U937 cells with phorbol 12-myristate 13-acetate (PMA),
      which activates protein kinase C (PKC), for 1 hr reduced the total number, but
      not the affinity, of PGE2 R by down-regulating principally EP2 R. In contrast, a
      24-hr exposure to PMA, which is known to down-regulate PKC, suppressed both the
      total number and affinity of PGE2 R on U937 cells with concurrent reductions in
      EP2 R and EP3 R. The down-regulation of EP2 R by PMA at 1 hr was blocked by
      staurosporine, an inhibitor of PKC, whereas the down-regulation of EP3 R by PMA
      at 24 hr was blocked by indomethacin. Pretreatment of U937 cells with PGE2 for 1
      and 24 hr reduced both the binding affinity and the total number of PGE2 R, by co
      ordinate suppression of the EP2 R and EP3 R. Desensitization of EP2 R and EP3 R
      for 1 hr with PGE2 suppressed subsequent PGE2-evoked chemokinetic responses to
      PGE2, whereas selective down-regulation of EP2 R alone by PMA for 1 hr had no
      effects on U937 cell migration. Thus expression of each subtype of PGE2 R is
      regulated independently and EP3 R, but not EP2 R, transduces PGE2 effects on
      migration of mononuclear phagocytes.

PMID- 8567031
TI  - Serine protease inhibitors block priming of monocytes for enhanced release of
      superoxide.
AB  - Monocytes freshly isolated from human blood produced large amounts of superoxide
      when triggered by phorbol ester. After monocytes were cultured for 18-24 hr in
      endotoxin-free, non-adherent conditions, they produced low amounts of superoxide.
      Addition of lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), tumour
      necrosis factor-alpha (TNF-alpha), or platelet-activating factor (PAF) at the
      beginning of culture 'primed' the monocytes, causing them to maintain a high
      superoxide response for at least 96 hr. Also, in response to LPS, monocytes
      secreted TNF-alpha. The ability of LPS, IFN-gamma, TNF-alpha or PAF to maintain
      the high superoxide response was blocked by addition of inhibitors of serine
      proteases, either 4-(2-aminoethyl)-benzenesulphonyl fluoride (AEBSF) or 3,4
      dichloroisocoumarin. AEBSF was most effective at 200 microns, and required 6 hr
      for maximum effect. AEBSF did not affect phorbol-triggered superoxide release by
      unprimed monocytes. AEBSF did not affect cell viability, nor did it interfere
      with the TNF-alpha secretion in response to LPS. An analogue of AEBSF that lacked
      ability to inhibit proteases did not affect monocyte responses. 3,4
      Dichloroisocoumarin blocked priming at a low concentration, 1 microM. We conclude
      that activity of a monocyte serine protease is required to maintain the high
      superoxide response in monocytes primed with LPS, IFN-gamma, TNF-alpha, or PAF.

PMID- 8567032
TI  - Impaired protein catabolism in Trypanosoma cruzi-infected macrophages: possible
      involvement in antigen presentation.
AB  - The effect of Trypanosoma cruzi infection on the ability of mature and immature
      murine peritoneal macrophage (MPM) subpopulations to catabolize the bacteriophage
      lambda repressor cI protein (cI) has been investigated. The capacity of infected
      MPM to present the cI and to stimulate various CD4+, I-Ad- or I-Ed-restricted T
      cell hybridomas specific for cI was also assessed. Our results show that the
      radioiodinated cI uptake and catabolism decreased sharply after infection of MPM
      with T. cruzi. A cI presentation deficiency appeared in mature and immature MPM
      infected with T. cruzi trypomastigotes. The ability of infected MPM to bind
      immunogenic cI (12-26) peptides to the plasma membrane Ia molecules was also
      altered, especially in immature MPM, as shown with paraformaldehyde prefixed MPM,
      suggesting that these MPM only have a few functional Ia molecules on their
      membrane. The reduced capacity of cI presentation to the I-Ed-restricted B26.1
      hybridomas by infected MPM subpopulations was comparable to that of the I-Ad
      restricted B24.4 and B26.2 T cells. The percentage of major histocompatibility
      complex (MHC) class II-positive MPM was also reduced after T. cruzi infection.
      The percentage of positive interleukin-2 receptor (IL-2R) MPM was sharply lowered
      in infected cells, even with a pre- or a post-interferon-gamma (IFN-gamma)
      activation. Finally, inhibition of prostaglandin with indomethacin, or of nitric
      oxide with N-monomethyl-L-arginine, or of tumour necrosis factor-alpha (TNF
      alpha) with specific monoclonal antibodies did not restore the cI presentation
      capacities of the MPM subpopulations. Taken together, these results suggest that
      T. cruzi infection induces a reduced capacity for macrophages to take up and
      catabolize antigen, resulting in a deficient antigen processing and presentation
      of the derived immunogenic peptides to specific CD4+ T-helper type-1 cell
      hybridomas. The decreased cI presenting capacity was a function of the cell's
      burden and maturity.

PMID- 8567033
TI  - Effect of nitric oxide donors on neutrophil responses induced by immune
      complexes.
AB  - The present study characterizes the effect of two nitric oxide (NO) donors, S
      nitrosoglutathione (GSNO) and sodium nitroprusside (SNP), on the ability of
      neutrophils to perform different responses triggered by immune complexes (IC).
      Pretreatment of neutrophils with either GSNO or SNP exerted a biphasic action on
      antibody-dependent cellular cytotoxicity (ADCC) performed against erythrocytes
      (E) coated with IgG antibodies (IgG-E), depending on the amount of IgG employed.
      While with high amounts of antibodies ADCC was markedly inhibited, at low amounts
      of antibodies it was significantly increased. Both effects were prevented by
      haemoglobin, a NO scavenger. Moreover, these effects were reproduced by the cell
      permeable analogue of cGMP, dibutyryl cGMP (Bt2cGMP). Other neutrophil functions
      triggered by IgG-E were also examined. It was found that NO donors did not affect
      either the phagocytosis of IgG-E or the emission of chemiluminescence (CL).
      Finally, neutrophil functions triggered by soluble IC (sIC) and precipitating IC
      (pIC) were analysed. It was observed that NO donors did not modify either
      cytotoxicity performed towards non-sensitized target cells or CL emission. The
      significance of these results is discussed.

PMID- 8567034
TI  - Apoptosis is associated with reduced expression of complement regulatory
      molecules, adhesion molecules and other receptors on polymorphonuclear
      leucocytes: functional relevance and role in inflammation.
AB  - Human polymorphonuclear leucocytes (PMN) express proteins that protect them from
      damage by homologous complement. Protection may be particularly important when
      these cells migrate to inflammatory sites where complement activation is taking
      place. Resolution of inflammation involves removal of these PMN. The major
      mechanism of removal is likely to involve PMN apoptosis followed by recognition
      and engulfment by macrophages. However, little attention has been paid to the
      possible relevance of apoptosis to PMN susceptibility to immune effectors. Here
      we describe a reduction in cell surface expression of two complement regulatory
      proteins, CD59, an inhibitor of the membrane attack complex and CD55 (decay
      accelerating factor), an inhibitor of the C3/C5 convertase, on a subpopulation of
      PMN aged in culture. Loss of these proteins, both attached to the membrane by
      glycosyl phosphatidylinositol (GPI) anchors, correlated closely with the
      appearance of apoptotic morphology. We also observed a marked reduction in
      expression of the GPI-anchored molecule CD16 on apoptotic PMN. Reduced expression
      of membrane proteins was not confined to those anchored through GPI--several
      transmembrane molecules including CD11a CD11b and CD18 were also reduced on
      apoptotic PMN, whilst other were little changed (CD35, CD46). The precipitous
      fall in CD16 surface expression on PMN was not specific for apoptosis--in vitro
      incubation of PMN with lipopolysaccharide-inhibited apoptosis but caused a
      reduction in CD16 expression to 'apoptotic' levels.

PMID- 8567035
TI  - Sensitizing capacity of Langerhans' cells obtained from ultraviolet-B-exposed
      murine skin.
AB  - Acute low-dose ultraviolet B (UVB) radiation impairs contact hypersensitivity
      induction in some strains of mice (called UVB-susceptible, UVB-S), but not in
      others (called UVB-resistant, UVB-R). In order to determine whether these UVB
      dependent phenotypes are inherent properties of epidermal Langerhans' cells, Ia
      enriched epidermal cell suspensions were prepared from normal and UVB-exposed
      skin of C57BL/6 (UVB-S) and BALB/c (UVB-R) mice. After derivatization with
      dinitrofluorobenzene (DNFB), the cells were injected into footpads of naive
      syngeneic mice, and the recipients were evaluated for contact hypersensitivity
      and for in vitro evidence of hapten-specific T-cell priming. The results indicate
      that DNFB-conjugated Ia-enriched epidermal cells from normal mice, and from UVB
      exposed skin of UVB-R mice induced contact hypersensitivity and primed hapten
      specific T cells in the draining lymph node. By contrast, epidermal cells from
      UVB-exposed skin of UVB-S mice failed to induce contact hypersensitivity, even
      though hapten-specific T cells were still detectable in the draining lymph node.
      In addition, UVB radiation impaired the ability of hapten-bearing Langerhans'
      cells from UVB-S mice to activate hapten-specific, primed T cells in vitro. We
      conclude the traits of UVB-S and UVB-R can be expressed directly by Langerhans'
      cells, and that these effects are at least in part responsible for the
      deleterious consequences of UVB radiation on cutaneous immunity in UVB-S mice.

PMID- 8567036
TI  - Effects of increased pulse pressure on cerebral arterioles.
AB  - The goal of this study was to examine the hypothesis that increases in pulse
      pressure produce hypertrophy of cerebral arterioles, even in the absence of
      increases in mean pressure. Sprague-Dawley rats underwent creation of an
      arteriovenous fistula and clipping of one carotid artery at 1 month of age. Rats
      that underwent exposure of the abdominal aorta without fistula production and
      unilateral carotid clipping served as controls. At about 6 months of age, the
      mechanics of sham and clipped pial arterioles were examined in vivo in
      anesthetized rats. Stress-strain relations were calculated from measurements of
      pial arteriolar pressure (servo null) and diameter and cross-sectional area of
      the arteriolar wall. Point counting stereology was used to quantify individual
      components in the arteriolar wall. Before deactivation of smooth muscle with
      EDTA, cross-sectional areas of the vessel wall and pulse pressures in sham pial
      arterioles were significantly greater (P < .05) in arteriovenous fistula rats
      than in control rats (cross-sectional area, 1468 +/- 100 versus 1129 +/- 104
      microns 2; pulse pressure, 26 +/- 1 versus 14 +/- 1 mm Hg). In contrast, systolic
      and mean pressures in sham arterioles were not significantly different and
      diastolic pressure was significantly less in arteriovenous fistula rats (systolic
      pressure, 69 +/- 1 versus 67 +/- 4 mm Hg; mean pressure, 52 +/- 2 versus 57 +/- 3
      mm Hg; diastolic pressure, 43 +/- 2 versus 53 +/- 3 mm Hg). Carotid clipping
      normalized cross-sectional area of the vessel wall (1083 +/- 86 microns 2) and
      pulse pressure (12 +/- 1 mm Hg) in pial arterioles of arteriovenous fistula rats.
      During maximal dilatation, the stress-strain curve in sham arterioles of
      arteriovenous fistula rats was shifted to the right of the curve in control rats,
      which indicates that arteriovenous fistulae increase passive distensibility of
      cerebral arterioles. The proportion of distensible components in the vessel wall
      (smooth muscle, elastin, and endothelium) was increased in sham arterioles of
      arteriovenous fistula rats. These findings (1) suggest that increases in pulse
      pressure, even in the absence of increases in mean pressure, are sufficient to
      produce hypertrophy of cerebral arterioles and (2) provide support for the
      concept that increases in distensibility of cerebral arterioles in association
      with hypertrophy of the vessel wall may be related to alterations in wall
      composition.

PMID- 8567037
TI  - Validation of carotid artery tonometry as a means of estimating augmentation
      index of ascending aortic pressure.
AB  - Our objective was to validate a carotid artery tonometry-derived augmentation
      index as a means to estimate augmentation index (AI) of ascending aortic pressure
      under various physiological conditions. A total of 66 patients (50 men, 16 women;
      mean age, 55 years; range, 21 to 78 years; 44 in Taiwan and 22 in the United
      States) undergoing diagnostic catheterization were studied. Arterial pressure
      contours were obtained simultaneously from the right common carotid artery by
      applanation tonometry with an external micromanometer-tipped probe and from the
      ascending aorta by a micromanometer-tipped catheter at baseline (n = 62), after
      handgrip (n = 36), or after sublingual nitroglycerin administration (n = 17). The
      AI (expressed as percentage values) was calculated as the ratio of amplitude of
      the pressure wave above its systolic shoulder to the total pulse pressure. The
      carotid AI was consistently lower than the aortic AI, but the two were highly
      correlated at baseline and after both handgrip and nitroglycerin. Mean +/- SD and
      correlation coefficients were baseline (14 +/- 16, 28(+) +/- 17, .77), handgrip
      (18 +/- 19, 32(+) +/- 15, .86), and nitroglycerin (7 +/- 12, 18(+) +/- 13, .52).
      In addition, after adjusting for age, sex, height, blood pressure, heart rate,
      and study site, the changes of both AIs from baseline values with handgrip or
      nitroglycerin were highly associated such that the aortic AI could be
      approximated from the carotid AI with appropriate regression equations. The high
      correlations and predictable changes after interventions between the central AI
      and those estimated from noninvasive carotid tonometry suggest that this
      technique may have wide applicability for many cardiovascular studies.

PMID- 8567038
TI  - ACE inhibition prevents and reverses L-NAME-exacerbated nephrosclerosis in
      spontaneously hypertensive rats.
AB  - Chronic nitric oxide inhibition exacerbates hypertension and nephrosclerosis in
      spontaneously hypertensive rats (SHRs). In this study, we determined whether
      angiotensin-converting enzyme (ACE) inhibition could prevent or reverse the
      systemic, renal, and glomerular hemodynamic alterations and the pathological
      changes of nephrosclerosis. Four groups of 20-week-old SHRs were studied: group
      1, untreated controls; group 2, treated with N omega-nitro-L-arginine methyl
      ester (L-NAME, 50 mg/L for 3 weeks); group 3, L-NAME cotreated with quinapril (3
      mg.kg-1.d-1 for 3 weeks); and group 4, L-NAME for 3 weeks followed by quinapril
      for 3 weeks (same doses). The results of this study demonstrated that both
      cotreatment (group 3) and posttreatment (group 4) with quinapril reduced mean
      arterial pressure (186 +/- 9 and 192 +/- 9 mm Hg, respectively, compared with
      group 2 SHRs, 221 +/- 5 mm Hg) and total peripheral resistance index associated
      with significant reductions in afferent and efferent arteriolar resistances;
      nephrosclerosis pathological scores; and urinary protein excretion (all at least
      P < .01). ACE inhibition also significantly increased stroke index, single
      nephron glomerular filtration rate, and ultrafiltration coefficient compared with
      the L-NAME SHRs. Most notable were the findings that cotreatment with quinapril
      completely prevented the renal glomerular hemodynamic alterations with reduced
      glomerular capillary hydrostatic pressure and efferent arteriolar resistance
      compared with both the untreated and the L-NAME-treated SHRs (all at least P <
      .01). Posttreatment with quinapril also reversed the glomerular injury
      (subcapsular, -83%; juxtamedullary, -56%) and arteriolar (-87%) injury scores
      obtained from renal biopsy specimens (P < .005 and P < .0001, respectively).
      These changes were associated with decreased periarteriolar fibronectin and
      increased afferent arteriolar alpha-smooth muscle actin deposition
      (immunohistochemistry). These data, therefore, demonstrate that ACE inhibition
      not only prevents but also reverses L-NAME-exacerbated severe nephrosclerosis in
      SHRs, as indicated by improved systemic, renal, and glomerular hemodynamic
      changes, proteinuria, and histological alterations.

PMID- 8567039
TI  - L-arginine prevents corticotropin-induced increases in blood pressure in the rat.
AB  - In this study we examined whether L-arginine treatment could prevent
      corticotropin (ACTH)-induced increases in blood pressure in the Sprague-Dawley
      rat. Sixty rats were randomly divided into six groups (n = 10): sham injection,
      ACTH injection (0.5 mg/kg per day in divided doses), L-arginine (0.6%) in food
      plus sham injection, L-arginine plus ACTH treatment, D-arginine (0.6%) in food
      plus sham injection, and D-arginine plus ACTH. Systolic pressure, water intake,
      urine volume, body weight, plasma and urinary electrolytes, and serum
      corticosterone concentrations were measured. ACTH increased systolic pressure
      (from 127 +/- 2 to 165 +/- 6 mm Hg, P < .001), water intake, and urine volume and
      decreased body weight body weight. L-Arginine reduced ACTH-induced blood pressure
      rises (130 +/- 3 mm Hg, P < .001) but had no effect on blood pressure in sham
      treated rats. D-Arginine did not affect blood pressure in sham-treated rats, and
      systolic pressure in D-arginine+ACTH-treated rats was similar to that of ACTH
      treated rats. L-Arginine decreased serum corticosterone concentrations in sham
      treated rats (424 +/- 42 versus 238 +/- 25 ng/mL, P < .01), but D-arginine had no
      effect. However, both drugs decreased serum corticosterone concentrations in ACTH
      treated rats (1071 +/- 117 versus 739 +/- 95 and 695 +/- 72 ng/mL for L- and D
      arginine, respectively; both P < .05). As L-arginine but not D-arginine prevented
      ACTH-induced increases in blood pressure in Sprague-Dawley rats and both L- and D
      arginine reduced serum corticosterone concentrations in ACTH-treated rats, the
      effects of L-arginine in preventing ACTH-induced hypertension were not simply a
      consequence of decreased corticosterone secretion.

PMID- 8567040
TI  - Increased vasoconstrictor sensitivity to glucocorticoids in essential
      hypertension.
AB  - Glucocorticoids raise blood pressure but were thought not to play a
      pathophysiological role in essential hypertension when it was demonstrated that
      cortisol secretion rates and circulating concentrations are normal in this
      disease. However, recent observations suggest that increased tissue sensitivity
      to cortisol, mediated by either abnormal glucocorticoid receptors or impaired
      inactivation of cortisol by 11 beta-dehydrogenase, may allow cortisol to raise
      blood pressure despite normal circulating concentrations. We studied 11 patients
      with essential hypertension and 11 matched normotensive control subjects. Dermal
      vasoconstriction after topical application of both cortisol (16 +/- 4 versus 32
      +/- 5 U, control subjects versus hypertensive patients; P < .02) and
      beclomethasone dipropionate (75 +/- 10 versus 100 +/- 7 U; P < .05) was increased
      in the hypertensive patients. Hypothalamic-pituitary glucocorticoid receptor
      sensitivity was normal, as judged by basal cortisol secretion rates and
      suppression of plasma cortisol during sequential overnight dexamethasone
      suppression tests. 11 beta-Dehydrogenase activity was impaired in essential
      hypertension, as judged by prolonged half-lives of [11 alpha-3H]cortisol (44 +/-
      4 versus 58 +/- 4 minutes, control subjects versus hypertensive patients; P <
      .02). However, this did not correlate with the dermal vasoconstrictor response.
      We conclude that vasoconstrictor sensitivity to glucocorticoids is increased in
      essential hypertension and that this may initiate and/or sustain the increased
      peripheral vascular resistance that characterizes this disease. The mechanism of
      increased sensitivity remains uncertain, but it will be important to establish
      whether it relates to genetic abnormalities of the glucocorticoid receptor that
      have been observed in animal models and young individuals who are predisposed to
      essential hypertension.

PMID- 8567041
TI  - Endogenous renal 11 beta-hydroxysteroid dehydrogenase inhibitory factors in
      patients with low-renin essential hypertension.
AB  - 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates the access of
      corticosteroids to their receptors and is important in blood pressure control.
      The excretion of renal 11 beta-HSD (ie, NAD(+)-dependent isoform) is thought to
      protect renal mineralocorticoid receptors from cortisol. To examine whether
      endogenous renal 11 beta-HSD inhibitory factor(s) may be involved in the
      pathophysiology of hypertension, we studied the urinary excretion of such
      inhibitors in 30 patients with low-renin essential hypertension and 20
      normotensive control subjects. The effect of sodium restriction on the urinary
      excretion of the inhibitors wa also evaluated in six normotensive control
      subjects. Urine was extracted with Sep-Pak cartridges and high-performance liquid
      chromatography. Endogenous renal 11 beta-HSD inhibitors were measured by the
      inhibition of 11 beta-HSD bioactivity in microsomes from the human kidney. The
      urinary excretion of the inhibitors was significantly increased in patients with
      low-renin essential hypertension (1280 +/- 88 nmol/d, mean +/- SEM) compared with
      normotensive control subjects (704 +/- 56 nmol/d) (P < .05). Ratios of urinary
      tetrahydrocortisol+allo-tetrahydrocortisol to tetrahydrocortisone did not differ
      significantly. Sodium restriction reduced the urinary excretion of the endogenous
      renal 11 beta-HSD inhibitors but did not affect the ratio of urinary
      tetrahydrocortisol+allo-tetrahydrocortisol to tetrahydrocortisone. Endogenous
      renal 11 beta-HSD inhibitory factors may contribute to the pathogenesis of low
      renin essential hypertension by modulating the activity of 11 beta-HSD. Sodium
      intake may directly or indirectly regulate the inhibitory factors.

PMID- 8567042
TI  - Does the renin-angiotensin system determine the renal and systemic hemodynamic
      response to sodium in patients with essential hypertension?
AB  - Many patients with essential hypertension respond to a high dietary sodium intake
      with a rise in blood pressure. Experimental evidence suggests that the renal
      hemodynamic response to sodium determines, at least partially, this rise in blood
      pressure. Our aim was to clarify the role of the renin-angiotensin system in the
      renal and systemic adaptation to a change in dietary sodium. We studied changes
      in mean arterial pressure (MAP) (millimeters of mercury), effective renal plasma
      flow (ERPF), body weight, and immunoreactive renin in 17 patients with essential
      hypertension and 15 normotensive control subjects, randomly crossing over between
      a 3-week sodium-restricted (50 mmol/24 h) and a sodium-replete (200 mmol/24 h)
      diet period. In addition, the effects of renin inhibition by remikiren (600 mg,
      single oral dose) were studied during the high sodium period. In normotensive
      control subjects, high sodium intake had no effect on MAP or body weight, whereas
      ERPF increased (490 +/- 19 to 535 +/- 21 mL/min, P < .05) and immunoreactive
      renin decreased (32 +/- 6 to 14 +/- 1 pg/mL). In hypertensive subjects, high
      sodium intake induced a heterogeneous response of MAP (median change, 2.6 mm Hg;
      range, -4.7 to +21.2; P = NS) and ERPF (median change, 21 mL/min; range, -33 to
      +98; P = NS). Body weight increased from 81.3 +/- 1.9 to 82.5 +/- 2.0 kg (P <
      .05), and immunoreactive renin decreased from 18 +/- 3 to 10 +/- 1 pg/mL (P <
      .05). Interestingly, the patients with a distinct rise in MAP showed a blunted
      ERPF response to high sodium intake (r = -.70, P < .01) and an increase in body
      weight (r = .76, P < .001). Moreover, the increase of ERPF was more pronounced in
      patients with a larger fall in immunoreactive renin (r = .77, P < .001). After
      administration of remikiren, a heterogeneous response in ERPF was observed: the
      patients with the blunted ERPF response to high sodium intake showed the largest
      ERPF rise (r = .70, P < .01). The remikiren-induced rise in ERPF correlated (r =
      .68, P < .01) with the fall in MAP (114 +/- 2 to 110 +/- 2 mm Hg). In conclusion,
      in patients with essential hypertension a rise in blood pressure in response to
      high sodium intake appears to partially be the result of insufficient renal
      vasodilatation. This seems to be due to an inadequate (intrarenal?) renin
      angiotensin system response to increased sodium intake.

PMID- 8567043
TI  - Comparison of early and late start of antihypertensive agents and baroreceptor
      reflexes.
AB  - Along with arterial blood pressure reduction, maintenance of the integrity of
      baroreceptor reflex function contributes to preserving end-organ function in the
      treatment of hypertensive patients. The purpose of this study was to investigate
      the effects of antihypertensive agents (trichlormethiazide, atenolol,
      nicardipine, and enalapril) on baroreceptor reflex function by comparing early
      and late starts of treatment. We administered each agent to spontaneously
      hypertensive rats (SHR) as early-start groups from 10 to 36 weeks of age and as
      late-start groups from 28 to 36 weeks of age. We evaluated the gain of the reflex
      control of renal sympathetic nerve activity and heart rate using ramp infusions
      of phenylephrine and nitroglycerin in untreated SHR at 10, 28, or 36 weeks of age
      and in treated SHR at 36 weeks of age. In 28- and 36-week-old untreated SHR, the
      renal sympathetic nerve activity gain was not altered and the heart rate gain was
      decreased (from -2.3 +/- 0.3 to -1.3 +/- 0.3 and -1.2 +/- 0.3 beats per minute
      [bm]/mm Hg, P < .05, respectively) compared with 10-week-old SHR. Early and late
      start of therapy produced arterial pressure reductions (-18 +/- 4 and -12 +/- 5
      mm Hg, P < .05, respectively). In the early-start groups, the renal sympathetic
      nerve activity gain was improved markedly in nicardipine- and enalapril-treated
      SHR (-4.2 +/- 0.2% and -4.9 +/- 0.2% of control/mm Hg, P < .01, respectively),
      and the heart rate gain was improved markedly in atenolol- and enalapril-treated
      SHR (-4.1 +/- 0.2 and -4.4 +/- 0.2 bpm/mm Hg, P < .01, respectively). In the late
      start groups, the renal sympathetic nerve activity gain was improved moderately
      in nicardipine- and enalapril-treated SHR (-3.8 +/- 0.2% and -2.9 +/- 0.2% of
      control/mm Hg, P < .05, respectively). The heart rate gain was improved slightly
      only in nicardipine-treated SHR (-1.9 +/- 0.2 bpm/mm Hg, P < .05). These results
      demonstrate that an early start of antihypertensive treatment improves
      baroreceptor reflex function markedly compared with a late start of treatment.
      This supports the hypothesis that a possible critical phase sensitive to
      intervention with antihypertensive treatment exists during the development of
      hypertension and indicates that the early start of antihypertensive treatment
      would be required in clinical practice.

PMID- 8567044
TI  - Pathophysiological consequences of changes in the coupling ratio of Na,K-ATPase
      for renal sodium reabsorption and its implications for hypertension.
AB  - Recent reports indicate that alpha 1-Na,K-ATPase from Dahl salt-sensitive (DS)
      rats contains a glutamine for leucine substitution associated with increased Na-K
      coupling at unchanged maximal velocity. Genetic analyses suggest that alpha 1
      Na,K-ATPase is a potential hypertension gene. Therefore, we investigated whether
      renal Na+ metabolism could constitute a pathophysiological link between the
      molecular/functional change in Na,K-ATPase and hypertension. We simulated the
      consequences of increased Na-K coupling on overall Na-bicarbonate reabsorption in
      a proximal tubular transport model that incorporates apical Na-H exchanger and
      basolateral Na-bicarbonate cotransporter, K+ channel, and Na,K-ATPase. As
      expected, increases in the levels of the former three transport pathways yielded
      higher Na+ reabsorption. In contrast, increases in the maximal velocity of the
      Na,K-ATPase with a normal 3:2 (Na-K) coupling ratio did not increase Na+
      reabsorption when apical Na-H exchange activity was limiting overall absorption.
      However, an increase in the Na-K coupling from 3:2 to 3:1, reported for the
      mutant alpha 1-Na,K-ATPase in DS rats, was associated with greater Na+
      reabsorption. This increase is a consequence of lower cytosolic pH and secondary
      stimulation of the Na-H exchanger at its allosteric H+ site. Decreased pH results
      from activation of Na-bicarbonate cotransport by Na,K-ATPase-dependent membrane
      hyperpolarization due to greater charge movement in 3:1 Na-K coupling. Thus, an
      increase in the Na-K coupling ratio results in an altered set point for cellular
      Na+ metabolism, with higher sodium reabsorption at unchanged Na,K-ATPase levels.
      The simulations thereby lend support for a unifying explanation for the salt
      sensitivity of DS rats, which has been proposed to stem from a mutation in the
      alpha 1-Na,K-ATPase.

PMID- 8567045
TI  - Indigo carmine inhibits endothelium-dependent and -independent vasodilation.
AB  - To investigate the potential mechanisms by which indigo carmine produces
      hypertension, we tested the hypothesis that indigo carmine inhibits endothelium
      dependent vasodilation and determined the possible site of the inhibition
      (endothelium versus smooth muscle). Using isolated rat thoracic aortic rings that
      were precontracted with phenylephrine, we examined vasodilatory responses to
      acetylcholine, histamine, and Ca2+ ionophore A23187 (in endothelium-intact rings)
      and sodium nitroprusside and isoproterenol (in endothelium-denuded rings) in the
      presence and absence of indigo carmine. In addition, the effects of methylene
      blue on the acetylcholine- and sodium nitroprusside-induced vasodilation were
      compared with those of indigo carmine. Indigo carmine (10(-6), 10(-5), and 10(-4)
      mol/L) significantly inhibited receptor- and non-receptor-mediated endothelium
      dependent vasorelaxation. Indigo carmine (10(-4) mol/L) also inhibited
      endothelium-independent vasorelaxation induced by sodium nitroprusside (an
      activator of vascular smooth muscle soluble guanylyl cyclase), although to a
      lesser extent than vasodilation from acetylcholine, histamine, and Ca2+ ionophore
      A23187. In contrast, indigo carmine (10(-4) mol/L) had no effect on the
      vasodilation induced by isoproterenol (an activator of adenylyl cyclase),
      indicating that indigo carmine selectively inhibits nitric oxide-mediated
      responses. Methylene blue, a known inhibitor of soluble guanylyl cyclase,
      inhibited both acetylcholine- and sodium nitroprusside-induced vasorelaxation.
      The inhibition was also greater in the acetylcholine- than the sodium
      nitroprusside-induced vasodilation. These results suggest that indigo carmine,
      like methylene blue, may inhibit endothelium-dependent relaxation by a mechanism
      that involves two levels. The major action of indigo carmine appears to be at the
      level of nitric oxide generation and/or release from the endothelial cell. In
      addition, indigo carmine appears to inhibit vascular smooth muscle guanylyl
      cyclase. Thus, indigo carmine may elevate blood pressure by interfering with
      these nitric oxide-mediated vasodilatory mechanisms.

PMID- 8567046
TI  - Role of kinins in the renal response to enalaprilat in normotensive and
      hypertensive rats.
AB  - This study examined the role of endogenous kinins in the alteration of renal
      hemodynamics induced by low-dose converting enzyme inhibition in hydropenic
      normotensive rats and in the nonclipped kidney of hydropenic two-kidney, one clip
      hypertensive rats. Infusion of a bradykinin B2 receptor antagonist (D
      Arg0,[Hyp3,Thi5,8,D-Phe7]-bradykinin, 1 or 10 micrograms.kg-1.min-1) did not
      alter renal function of normotensive rats. In a second series of experiments,
      infusion of enalaprilat at 0.1 mg.kg-1.h-1 increased renal blood flow (P < .01)
      and decreased renal vascular resistance (P < .01). The superimposition of the
      kinin antagonist at 1 micrograms.kg.min-1 during the enalaprilat infusion
      decreased renal blood flow to a value similar to the preenalaprilat baseline and
      significantly different from the mean of the two enalaprilat periods before and
      after the addition of the kinin antagonist--the "mean effect of enalaprilat." The
      decrease in renal blood flow induced by the kinin antagonist was associated with
      an increase in renal vascular resistance above the mean effect of enalaprilat (P
      < .025). In two-kidney, one clip hypertensive rats, systemic infusion of
      enalaprilat augmented the hemodynamics of the nonclipped kidney by a degree
      similar to that in normotensive rats. In contrast to normotensive rats,
      superimposition of the kinin antagonist did not alter the enalaprilat-induced
      change in blood flow or vascular resistance of the nonclipped kidney. The results
      of this study suggest that endogenous kinins contribute to the increased renal
      function induced by low-dose converting enzyme inhibition in hydropenic
      normotensive rats but appear to contribute less to the enalaprilat-induced
      alterations of renal function in the nonclipped kidney of two-kidney, one clip
      hypertensive rats.

PMID- 8567047
TI  - Effects of amlodipine on glomerular filtration, growth, and injury in
      experimental hypertension.
AB  - The objective of this study was to determine whether the calcium antagonist
      amlodipine could slow the progression of chronic renal disease. We examined the
      effects of amlodipine on kidney structure and function in two experimental models
      of hypertension. In the first study, adult, male Munich Wistar rats underwent
      uninephrectomy and were given weekly injections of desoxycorticosterone and 1%
      saline for drinking. Rats ingested normal chow or chow containing amlodipine for
      8 weeks. The drug reduced systemic blood pressure, but glomerular filtration
      rate, kidney weight, proteinuria, and morphological evidence of glomerular injury
      were not affected. In the second study, male spontaneously hypertensive rats
      underwent uninephrectomy at 5 weeks of age and were followed for 6 months, during
      which they received no therapy or amlodipine. The drug dose was determined in
      preliminary studies to be the highest dose not associated with marked growth
      retardation. Again, although systemic blood pressure was significantly reduced by
      amlodipine, proteinuria and the prevalence of glomerulosclerosis were similar in
      amlodipine-treated and control spontaneously hypertensive rats. Micropuncture
      studies revealed that glomerular pressure remained elevated in amlodipine-treated
      spontaneously hypertensive rats. Kidney weight and glomerular volume were also
      similar in amlodipine-treated and control rats. Amlodipine also failed to inhibit
      platelet aggregation. Therefore, antihypertensive therapy with amlodipine fails
      to reduce glomerular pressure in spontaneously hypertensive rats as well as
      glomerular size and injury in spontaneously hypertension rats and
      desoxycorticosterone-salt hypertension. Although other dihydropyridine calcium
      antagonists have been found to reduce experimental glomerular injury, these data
      suggest that amlodipine may not prevent hypertensive nephrosclerosis.

PMID- 8567048
TI  - Time-voltage area of the QRS for the identification of left ventricular
      hypertrophy.
AB  - Standard electrocardiographic criteria have exhibited poor sensitivity for left
      ventricular hypertrophy at acceptable levels of specificity and perform less well
      in women than men, even when sex-specific criteria are used. The time-voltage
      integral of the horizontal plane vector QRS complex can improve identification of
      hypertrophy in men, but performance of this approach in women and the effect of
      sex-specific criteria on accuracy have not been examined. To evaluate the
      accuracy of the time-voltage integral of the QRS complex for the identification
      of left ventricular hypertrophy in women and to examine the effect of sex-and non
      sex-specific criteria on test performance, we obtained standard 12-lead and
      orthogonal-lead signal-averaged electrocardiograms and echocardiograms in 175
      control subjects without hypertrophy (43 women and 132 men) and 75 patients with
      hypertrophy (26 women and 49 men) defined by echocardiographic criteria (indexed
      left ventricular mass > 110 g/m2 in women and > 125 g/m2 in men). Voltage of the
      QRS complex was integrated over the total QRS duration in leads X and Z for
      calculation of the time-voltage integral of the horizontal plane vector complex.
      With the use of a partition of 99.2 microV.s with a specificity of 98% in the
      entire normal group, sensitivity of the horizontal plane vector integral was
      significantly lower in women than men (31% versus 71%, P < .001). In contrast,
      use of sex-specific partitions of 75.4 microV.s in women and 99.2 microV.s in men
      with matched 98% specificity significantly improved sensitivity in women to 81%
      (P < .001), with no change in sensitivity in men (71%). Comparison of receiver
      operating characteristic curves with the use of sex-specific criteria
      demonstrated no significant difference in overall performance of the horizontal
      plane vector integral between men and women. The 81% and 71% sensitivities of the
      sex-specific horizontal plane vector integral were significantly greater than the
      27% to 58% sensitivities of sex-specific 12-lead electrocardiographic criteria in
      this population. Thus, sex-specific criteria significantly improve performance of
      the time-voltage integral of the QRS for the identification of left ventricular
      hypertrophy in women, with no loss of accuracy in men. Use of the time-voltage
      integral can improve the accuracy of the electrocardiogram for the identification
      of left ventricular hypertrophy in both women and men.

PMID- 8567049
TI  - Endothelin-1 and its receptor in hypertrophic cardiomyopathy.
AB  - Endothelin-1, a potent vasoconstrictor produced by vascular endothelial cells,
      activates the hypertrophic program in cultured heart muscle cells. However, the
      role of endothelin-1 in cardiac hypertrophy in humans is unknown. Therefore, we
      studied hypertrophic cardiomyopathy patients with normal pulmonary arterial
      pressure, in whom cardiac hypertrophy is a specific feature of the disease.
      Radioimmunoassay with a monoclonal antibody to human endothelin-1 showed that the
      plasma level of immunoreactive endothelin was more than twofold higher in
      hypertrophic cardiomyopathy patients than in control subjects (P < .005). In situ
      hybridization analysis of endomyocardial biopsy specimens showed positive signals
      of endothelin-1 type A receptor mRNA in ventricular myocytes of all specimens.
      The receptor expression in ventricular myocytes was similar between hypertrophic
      cardiomyopathy patients and control subjects. We propose that endothelin-1 might
      represent an important factor involved in hypertrophic cardiomyopathy. Whether
      endothelin-1 plays a causal role in cardiac hypertrophy or is a marker of its
      occurrence needs to be clarified.

PMID- 8567050
TI  - Impaired regulation of cell communication by beta-adrenergic receptor activation
      in the failing heart.
AB  - We investigated the influence of beta-adrenergic receptor activation on the
      control of gap junctional conductance (gj) in the heart of cardiomyopathic
      hamsters (11 months old). We measured gj in isolated ventricular cell pairs using
      two voltage-clamp circuits. Administration of isoproterenol (10(-6) mol/L) to the
      bath had no effect on gj in myopathic cell pairs but increased gj by 45 +/- 3%
      (+/- SE) in normal hamsters. Moreover, forskolin (10(-7) mol/L), an activator of
      adenyl cyclase, did not change gj in myopathic cells but enhanced gj by 23 +/-
      2.8% in controls. Similar results were obtained with isobutylmethylxanthine (10(
      6) mol/L), a phosphodiesterase inhibitor. Dibutyryl-cAMP (10(-6) mol/L), however,
      increased gj of cardiomyopathic cell pairs by 58 +/- 2.1% within 2 minutes and
      enhanced gj in controls by 50 +/- 3.6%. The effect of dibutyryl-cAMP on gj of
      myopathic cells was suppressed by intracellular dialysis of an inhibitor of
      protein kinase A. These observations indicate that the regulation of gj by the
      beta-adrenergic receptor-G protein-adenyl cyclase signaling system is greatly
      impaired in the failing heart but the ability of cAMP to increase gj is still
      preserved.

PMID- 8567051
TI  - Protein kinase C modulation of cardiomyocyte angiotensin II and vasopressin
      receptor desensitization.
AB  - Angiotensin II (Ang II) and arginine vasopressin (AVP) increased intracellular
      free Ca2+ concentration [Ca2+]i and/or the [Ca2+]i transient rate (CaTR) in
      cultured neonatal rat cardiomyocytes. These agents increased membrane-bound
      protein kinase C (PKC) with peak activity at 5 and 10 minutes, respectively. Two
      minute exposure to Ang II produced homologous desensitization to a repeated
      stimulation with Ang II and heterologous desensitization to AVP. Two-minute
      exposure to AVP also produced homologous desensitization to AVP but not
      heterologous desensitization to Ang II. When the AVP exposure time was increased
      from 2 to 10 minutes coincident with maximal AVP-mediated PKC activation,
      heterologous desensitization to Ang II was also observed. Acute activation (15
      minutes) of PKC by phorbol 12-myristate 13-acetate (PMA) blocked responsiveness
      to both Ang II and AVP. When PKC activation was inhibited by 20 hours of prior
      exposure to PMA, as confirmed by PKC assay, homologous desensitization of Ang II
      still occurred, confirming an alternative mechanism(s) for homologous
      desensitization in the cardiomyocytes. In contrast, 20-hour PMA suppression of
      PKC markedly diminished the ability of the cardiomyocytes to exhibit AVP-mediated
      heterologous desensitization for Ang II. These data indicate that PKC activation
      plays a primary role in mediating vasopressin V1 receptor-induced heterologous
      desensitization of the Ang II receptor and participates in a hierarchy of two or
      more kinase systems mediating homologous desensitization of the Ang II receptor
      in cardiomyocytes.

PMID- 8567052
TI  - Sympathetic nerve activity and insulin in obese normotensive and hypertensive
      men.
AB  - The relationship between resting levels of muscle sympathetic nerve activity
      (MSA) and blood pressure is a matter of controversy. Body weight has recently
      been identified as an independent determinant of muscle sympathetic discharge,
      which may have influenced previous studies focused on MSA and mechanisms of
      hypertension. In the present study, we measured resting MSA and plasma insulin
      levels in 18 obese (body mass index, 32 +/- 4 kg/m2) (mean +/- SD), middle-aged
      (52 +/- 6 years), hypertensive (155 +/- 11/97 +/- 8 mm Hg) subjects and 16 age-
      and body mass index-matched normotensive control subjects. In the postabsorptive
      state, resting MSA was similar in the hypertensive and normotensive groups (43 +/
      4 versus 39 +/- 3 bursts per minute, 69 +/- 5 versus 64 +/- 5 bursts per 100
      heart beats, P = NS) (mean +/- SEM) and did not correlate with either systolic or
      diastolic blood pressure. Weak but significant positive correlations were found
      between resting MSA and both fasting insulin levels (P < .05) and body mass index
      (P = .05) in hypertensive but not normotensive subjects. There was a strong
      positive correlation between fasting insulin and body mass index in both
      normotensive subjects and the entire study group (P < .005). Fasting insulin and
      body mass index correlated with diastolic blood pressure (P < .05) in the entire
      study group. In conclusion, a relationship between fasting insulin, body mass
      index, and blood pressure was confirmed, whereas only a weak correlation was
      found between MSA and fasting insulin in hypertensive but not normotensive
      subjects. The fact that MSA was similar in the two groups argues strongly against
      augmented MSA being important for the maintenance of hypertension, at least in
      middle-aged, obese men.

PMID- 8567053
TI  - Activation of angiotensin-generating systems in the developing rat kidney.
AB  - The present study was designed to determine the developmental changes in
      intrarenal angiotensin (Ang) peptides in the rat. Kidney Ang I and II levels were
      threefold and sixfold higher in newborn than adult kidneys, respectively (Ang I,
      678 +/- 180 versus 243 +/- 38 fmol/g, P < .01; Ang II, 667 +/- 75 versus 103 +/-
      6 fmol/g, P < .001). Intrarenal Ang II levels correlated positively with the
      temporal changes in renin gene expression (r = .93, P < .001). However, no
      correlation was found between renal Ang II content and angiotensin-converting
      enzyme (ACE) expression during development, which prompted us to evaluate whether
      renal enzymes, other than renin and ACE, contribute to Ang II formation in the
      developing kidney. Angiotensin peptide levels were measured in newborn and adult
      kidney homogenates incubated with human angiotensinogen (a poor rat renin
      substrate) for 30 minutes at 37 degrees C. Inhibitors of aspartyl proteases and
      metalloproteases were ineffective in preventing the formation of Ang II in either
      newborn or adult kidneys. However, addition of the serine protease inhibitors
      soybean trypsin inhibitor and phenylmethylsulfonyl fluoride inhibited Ang II
      generation in the newborn kidneys only. In contrast, Ang I generation was not
      affected by inhibition of serine proteases in either newborn or adult kidneys. We
      conclude that Ang I and II synthesis is activated in the developing rat kidney.
      In addition to renin and ACE, the newborn rat kidney expresses serine protease
      activity that is capable of generating Ang II directly from angiotensinogen. This
      putative enzyme is induced in the newborn kidney and may cooperate with renin in
      the activation of Ang II synthesis during early development.

PMID- 8567054
TI  - Medullary neurons activated by angiotensin II in the conscious rabbit.
AB  - Previous studies have shown that angiotensin II (Ang II) can activate
      cardiovascular neurons within the medulla oblongata via an action on specific
      receptors. The purpose of this study was to determine the distribution of neurons
      within the medulla activated by infusion of Ang II into the fourth ventricle of
      conscious rabbits, using the expression of Fos, the protein product of the
      immediate early gene c-fos as a marker of neuronal activation. Experiments were
      done in both intact and barodenervated animals. In comparison with a control
      group infused with Ringer's solution alone, in both intact and barodenervated
      animals, fourth ventricular infusion of Ang II (4 to 8 pmol/min) induced a
      significant increase in the number of Fos-positive neurons in the nucleus of the
      solitary tract and in the rostral, intermediate, and caudal parts of the
      ventrolateral medulla. Double-labeling for Fos and tyrosine hydroxylase
      immunoreactivity showed that 50% to 75% of Fos-positive cells in the rostral,
      intermediate, and caudal ventrolateral medulla and 30% to 40% of Fos-positive
      cells in the nucleus of the solitary tract were also positive for tyrosine
      hydroxylase in both intact and barodenervated animals. The distribution of Fos
      positive neurons corresponded very closely to the location of Ang II receptor
      binding sites as previously determined in the rabbit. The results indicate that
      medullary neurons activated by Ang II are located in discrete regions within the
      nucleus of the solitary tract and ventrolateral medulla and include, in all of
      these regions, both catecholamine and noncatecholamine neurons.

PMID- 8567055
TI  - Atrial natriuretic peptide blunts arterial baroreflex in spontaneously
      hypertensive rats.
AB  - We and other laboratories have reported that arterial baroreflex-mediated control
      of heart rate is blunted in spontaneously hypertensive rats (SHR) compared with
      normotensive controls. Recently, we reported that atrial natriuretic peptide
      (ANP) microinjected into the caudal nucleus tractus solitarii of SHR further
      blunts this defect. The present study tested the hypothesis that ANP modulates
      arterial baroreflex-mediated control of sympathetic nervous system activity. Nine
      week-old, male SHR (n = 29) and normotensive Wistar-Kyoto control rats (n = 24)
      were instrumented for microinjection into the caudal nucleus tractus solitarii
      and for direct measurement of arterial blood pressure, heart rate, and lumbar
      sympathetic nervous system activity. After urethane- and alpha-chloralose-induced
      induced anesthesia, arterial baroreflex-mediated control of heart rate and lumbar
      sympathetic nerve activity was assessed during phenylephrine- (5 to 40
      micrograms.kg-1.min-1) induced increases and sodium nitroprusside- (15 to 300
      micrograms.kg-1.min-1) induced decreases in mean blood pressure before and after
      microinjection of ANP (50 ng) or monoclonal antibody to ANP (0.55 micrograms)
      into the caudal nucleus tractus solitarii. ANP reduced and the antibody enhanced
      the sensitivity of baroreflex-mediated control of both heart rate and lumbar
      sympathetic nerve activity in SHR but not in Wistar-Kyoto controls (P < .05).
      Arterial baroreflex sensitivity was unchanged with control microinjections of
      vehicle or mouse IgG in SHR. These data suggest that endogenous ANP in the caudal
      nucleus tractus solitarii may contribute to the development and/or maintenance of
      hypertension in SHR by blunting baroreflex-mediated control of sympathetic
      nervous system activity.

PMID- 8567056
TI  - Serum fatty acids and blood pressure.
AB  - To examine the relation between serum fatty acids and blood pressure, we
      conducted a cross-sectional study of 156 men who were enrolled in the Multiple
      Risk Factor Intervention Trial. After confirming the stability of the stored
      serum samples, we measured serum fatty acid levels by gas-liquid chromatography
      and examined their association with blood pressure. Using stepwise linear
      regression, we determined that each SD increase (1.9%) in the serum level of
      cholesterol ester palmitoleic acid (16:1) was associated with a systolic pressure
      increase of 3.3 mm Hg (95% confidence interval, 0.9 to 5.6 mm Hg) and each SD
      increase (0.1%) in phospholipid omega 9 eicosatrienoic acid (20:3) was associated
      with a diastolic pressure increase of 1.7 mm Hg (95% confidence interval, 0.5 to
      2.9 mm Hg). Serum level of cholesterol ester steric acid (18:0) was inversely
      associated with diastolic pressure: each SD increase (0.2%) was associated with a
      decrease of 1.4 mm Hg (95% confidence interval, -2.5 to -0.2 mm Hg). In
      multivariate models that included dietary fat intake, cholesterol ester
      dihomogammalinolenic acid (20:3) was also associated with diastolic pressure:
      each SD increase (0.16%) was associated with an increase of 1.2 mm Hg (95%
      confidence interval, 0.1 to 2.4 mm Hg). Our results indicate that three
      nonessential fatty acids--stearic acid, palmitoleic acid, and omega 9
      eicosatrienoic acid, and one essential fatty acid--dihomogammalinolenic acid, are
      independent correlates of blood pressure among middle-aged American men at high
      risk of coronary heart disease.

PMID- 8567057
TI  - Genetic and biochemical factors associated with variation in blood pressure in a
      genetic isolate.
AB  - We previously found an association between blood pressure and genetic variation
      of angiotensinogen in Canadian Hutterites. We hypothesized that variation in
      other candidate genes would also be associated with variation in blood pressure.
      We included genotypes of 12 candidate genes, along with clinical features and
      biochemical variables as covariates in an association analysis. We found that sex
      and body mass were significantly associated with variation in both systolic and
      diastolic blood pressures. We found that genotypes of APOB codon 4154 and AGT
      codon 174 were significantly associated with variation in systolic blood
      pressure. We found that genotypes of APOB codon 4154, AGT codon 174, and F7 codon
      353 were significantly associated with variation in diastolic blood pressure. We
      found a significant association between age and variation in systolic but not
      diastolic blood pressure. We found a significant association between plasma apo B
      concentration and variation in diastolic but not systolic blood pressure. The
      association of genomic variation with resting blood pressure is consistent with
      the existence of important structural elements within or proximal to some genes
      in lipoprotein metabolism, the renin-angiotensin system, and the coagulation
      cascade. The association between plasma apo B concentration and diastolic blood
      pressure suggests that these traits may share some determinants.

PMID- 8567058
TI  - Measurement of forearm blood flow.

PMID- 8567059
TI  - Measurement of sodium-lithium countertransport kinetics.

PMID- 8567060
TI  - Measurement of sodium-lithium countertransport kinetics.

PMID- 8567061
TI  - Measurement of sodium-lithium countertransport kinetics.

PMID- 8567062
TI  - Glial reactivity in the retina of adult rats.
AB  - The present study aimed to characterize the reaction of mammalian (rat) retinal
      macroglia (Muller cells and astrocytes) to disturbances of their environment in
      the form of intraorbital section of the optic nerve, intraocular insertion of a
      thin glass capillary (without damage to the retina) or a combination of both.
      Glial reactivity was assessed through the use of a battery of antibodies which
      recognise four different proteins--glial fibrillary protein (GFAP) and three
      other proteins designated respectively MA1, 4D6 and 4H11. Retinal astrocytes did
      not exhibit any changes in normally expressed GFAP or MA1. By contrast, the
      expression of GFAP and MA1 in Muller cells increased 14 days following section of
      the optic nerve and/or intravitreal insertions of a glass capillary. Three days
      postoperatively, the expression of GFAP, but not MA1, had already increased
      significantly in Muller cells. 4D6 and 4H11 proteins were not expressed in
      astrocytes. In Muller cells, the levels of these proteins increased significantly
      following combined optic nerve section and intraocular insertion of a glass
      capillary. Thus, a mechanical disturbance of the intraocular environment
      constitutes a more effective stimulus in increasing the expression of some
      Mullerian proteins than damage to the axons of retinal ganglion cells. Such
      changes have important implications for various ocular treatments that involve
      intraocular administration of drugs, as well as for the survival/regeneration
      potential of retinal ganglion cells undergoing Wallerian degeneration.

PMID- 8567063
TI  - The role of intracellular calcium and protein kinase C in endothelin-stimulated
      proliferation of rat type I astrocytes.
AB  - The increased expression of immunoreactive endothelin-1 (ET-1) in reactive
      astrocytes and its mitogenic effects on astrocytes and glioma cell lines, have
      implicated endothelins in the development of reactive gliosis. In this study, an
      increase in DNA synthesis in rat type I astrocytes was observed after cultures
      were transiently exposed to ET-1 for 15 min, suggesting that early signal
      transduction events are essential and sufficient for the propagation of the ET-1
      induced mitogenic signal. Prompt increases in inositol triphosphate (IP3)
      formation and [Ca2+]i were observed upon the addition of ET-1 to these cells. The
      ET-1-evoked increase in [Ca2+]i consisted of an initial peak which was preserved
      in Ca(2+)-free medium, and a sustained phase which was abolished in Ca(2+)-free
      medium and partly attenuated by nifedipine. ET-1 also increased the activity of
      membrane-associated protein kinase C (PKC) and induced the in vivo
      phosphorylation of the 85 kD MARCKS protein, an endogenous PKC-specific
      substrate. The ET-1-evoked increases in DNA synthesis, IP3, [Ca2+]i, membrane
      PKC, and 85 kD MARCKS protein phosphorylation in rat cortical astrocytes were
      prevented by either the selective endothelin ETA receptor antagonist, BQ-123, or
      the phospholipase C (PLC)-specific inhibitor, U-73122. However, the inhibition of
      PKC activity did not affect ET-1-induced DNA synthesis in rat cortical
      astrocytes. These results suggest that ET-1-induced IP3 and/or [CA2+]i responses,
      but not the activation of PKC, are essential for the growth-factor like actions
      of ET-1 in rat cortical astrocytes.

PMID- 8567064
TI  - Relationship between astrocytic processes and "perineuronal nets" in rat
      neocortex.
AB  - "Perineuronal nets" (PNs) ensheath a subtype of inhibitory neurons in the
      mammalian neocortex. In the light of the proposal that PNs consist of glial
      processes, we have analyzed the relationship between intracellularly injected
      glial cells and PNs in the rat neocortex. Glial cells were injected
      iontophoretically with Lucifer Yellow in lightly fixed tissue slices and PNs were
      visualized with the lectin from Vicia villosa. Using confocal laser scanning
      microscopy, glial processes and PNs were identified as distinct structures.
      Lectin labeling was consistently associated with the extracellular space
      interposed between LY-labeling was consistently associated with the extracellular
      space interposed between LY-labeled astrocyte processes and neurons. Of the
      different types of glial cells injected, only the densely-ramifying protoplasmic
      astrocytes extended processes which could be traced to contact PNs. These
      protoplasmic astrocytes also sent out processes to adjacent neurons not
      ensheathed by PNs, and to capillaries. The present data strongly suggests that
      PNs do not consist of glial processes but rather support the idea that PNs
      represent specialized extracellular material interposed between the surface of
      some inhibitory interneurons and astrocytic processes.

PMID- 8567065
TI  - Amyloid precursor protein (APP) expression in multiple sclerosis lesions.
AB  - The amyloid precursor protein (APP) is rapidly induced in reactive glial cells in
      response to several pathological stimuli including inflammation. In the present
      study, observations previously made in animal models of autoimmune central
      nervous system inflammation have been extended to the analysis of multiple
      sclerosis (MS) lesions. A total of thirty fresh-frozen tissue blocks from six
      histopathologically normal control and six MS cases have been examined
      immunocytochemically with monoclonal antibodies directed against either C- or N
      terminal epitopes of APP. Histopathological evaluation of disease progression was
      based on hematoxylin-eosin and oil red O staining and immunocytochemistry for T
      cells, macrophages/microglia, astrocytes, and oligodendrocytes. In control cases,
      APP immunoreactivity was generally low and confined to blood vessel walls,
      oligodendrocytes in white, and neurons in grey matter. In actively demyelinating
      plaques, however, levels of APP immunoreactivity were high, localised on T
      lymphocytes, foamy macrophages, activated microglia, and reactive astrocytes
      including astrocytic processes. In more chronic lesions, levels of APP
      immunoreactivity were generally lower than in acute lesions, mainly found on
      reactive astrocytes, their processes and a few macrophages/microglia depending on
      the stage of plaque development. In addition, a few 14E-positive oligodendrocytes
      and, moreover, numerous axons exhibited APP immunoreactivity, which was
      particularly pronounced with anti-C-terminal antibodies. These results
      demonstrate that APP is induced on reactive glial cells but also on T lymphocytes
      during demyelination. The extent of APP expression appears to be correlated to
      histopathological lesion development and thus suggests that APP detection serves
      as a sensitive marker for disease progression in MS.

PMID- 8567066
TI  - Sodium-dependent glutamate uptake as an activator of oxidative metabolism in
      primary astrocyte cultures from newborn rat.
AB  - In the present report we describe the effect of glutamate on respiratory activity
      in primary cultures of astrocytes, derived from cerebral cortex of newborn rat.
      Glutamate (100 microM) caused an increased oxygen consumption. This effect could
      not be inhibited by antagonists to the NMDA or AMPA/kainate receptors. Neither
      trans-ACPD (an agonist to the metabotropic glutamate receptor) nor the Krebs
      cycle intermediate alpha-ketoglutarate had any effect on the respiratory rate. An
      uncontrolled influx of Na+, caused by gramicidin, could mimic the glutamate
      effect on respiratory activity. In addition, the glutamate effect was abolished
      by addition of ouabain or replacement of Na+ by Li+ in the perfusion buffer. We
      conclude that the co-transport of Na+, in the Na(+)-dependent high-affinity
      glutamate uptake system, mediated the glutamate-induced increase in oxygen
      consumption through an increased activity of Na+/K(+)-ATPases.

PMID- 8567067
TI  - Developmental pattern of GFAP and vimentin gene expression in rat brain and in
      radial glial cultures.
AB  - In the present study we analyze the events which occur during the early stages of
      astrogliogenesis by examining the pattern of both GFAP and vimentin gene
      expression and their corresponding immunoreactive proteins during rat brain
      development. This study was carried out "in vivo" (whole brain) and "in vitro"
      (primary culture of radial glia) using immunofluorescence, immunoblotting, and
      Northern blot analysis. Our results demonstrate that although GFAP immunostaining
      appeared late in gestation and at day 5 in radial glia cultures, GFAP mRNA
      expression was first detected, at very low levels, on fetal (F) day 15 and
      increased to F21. During postnatal development a striking increase in GFAP and
      its encoding messenger occurs. In contrast, the levels of vimentin and its mRNA
      expression were very high during the fetal stage (F15 to F21). Thereafter
      vimentin expression declined during postnatal (P) development until P21 and then
      remained constant at adult levels. In contrast, an increase in vimentin
      expression was observed in glial cells throughout the entire culture period. The
      biological significance of the developmental patterns of GFAP and vimentin
      expression in astroglial cells. during brain development is discussed.

PMID- 8567068
TI  - Evidence for cyclooxygenase activation by nitric oxide in astrocytes.
AB  - We have evaluated the role of nitric oxide (NO) on the cyclooxygenase pathway in
      mouse glial cells. Exposure of primary cultures of neonatal mouse cortical
      astrocytes to bacterial lipopolysaccharide (LPS; 1 microgram/ml, 18 h) caused an
      increase in the release of both nitrite (NO2-) and prostaglandin E2 (PGE2),
      products of NO synthase (NOS) and cyclooxygenase, respectively. Production of
      both, NO2- and PGE2 by astrocytes, was inhibited by the exposure of the NOS
      inhibitor Nw-nitro-L-arginine methyl ester (L-NAME: 1, 10, and 100 microM) in a
      dose related manner. Besides, other NOS inhibitors such as Nitro L-arginine (NNA:
      10(-3) M) prevented the increase in PGE2 release from LPS-stimulated astrocytes.
      Sodium nitroprusside (SNP; 100-200 microM) used as a NO donor caused a dose
      related enhancement in the accumulation of PGE2 induced by LPS and the presence
      of hemoglobin blocked the SNP effects. The exposure to SNP counteracted the
      decrease of PGE2 production in LPS-treated astrocytes in which NO synthesis was
      blocked by L-NAME. In addition, SNP also enhanced the synthesis of PGE2 following
      exogenous arachidonic acid astrocytes exposure. Interestingly, this effect was
      blocked by indomethacin. Treatment of astrocytes cultures with dexamethasone
      (0.1, 1 microM) blocked dose-relatedly the LPS-induced release of both NO2- and
      PGE2. As expected, the presence of indomethacin (1, 10, and 20 microM) prevented
      in a dose related fashion, PGE2 production by astrocytes following exposure to
      LPS. These results strongly indicate that in astroglial cells, NO is able to
      activate the cyclooxygenase pathway.

PMID- 8567069
TI  - Developmental regulation of Na+ and K+ conductances in glial cells of mouse
      hippocampal brain slices.
AB  - The relative contribution of voltage activated Na+ and K+ currents to the whole
      cell current pattern of hippocampal glial cells was analyzed and compared during
      different stages of postnatal maturation. The patch-clamp technique was applied
      to identified cells in thin brain slices obtained from animals between postnatal
      day 5 and 35 (p5-35). We focused on a subpopulation of glial cells in the CA1
      stratum radiatum which most probably represents a pool of immature astrocytes,
      termed "complex" cells. These cells could not be labelled by O1/O4 antibodies,
      but some of the older cells were positively stained for glial fibrillary acidic
      protein (GFAP). In the early postnatal days, the current pattern of the "complex"
      cells was dominated by two types of K+ outward currents: a delayed rectifier and
      a transient component. In addition, all cells expressed significant tetrodotoxin
      (TTX)-sensitive Na+ currents. During maturation, the contribution of delayed
      rectifier and A-type currents significantly decreased. Furthermore, almost all
      cells after p20 lacked Na+ currents. This down-regulation of voltage gated Na+
      and K+ outward currents was accompanied by a substantial increase in passive and
      inward rectifier K+ conductances. We found increasing evidence of electrical
      coupling between the "complex" cells with continued development. It is concluded
      that these developmental changes in the electrophysiological properties of
      "complex" glial cells could be jointly responsible for the well known impaired K+
      homeostasis in the early postnatal hippocampus.

PMID- 8567070
TI  - Na+ channel aggregation in remyelinating mouse sciatic axons following
      transection.
AB  - Mouse sciatic nerves from the degeneration-resistant strain C57BL/6/Wld (Ola)
      were surgically injected with lysolecithin to induce focal demyelination. Three
      days later they were transected adjacent to the spinal cord to eliminate contact
      of the axons with their cell bodies. The Na+ channel distribution was assessed by
      immunocytochemistry and followed at several stages of remyelination. Control
      experiments were performed on nerves that were injected but not cut. At (3 + 4)
      days, namely, nerves cut 3 days post-injection and examined 4 days after cutting,
      axons contained fully demyelinated regions. Na+ channel clusters appeared only at
      heminodes and at isolated sites that are likely to represent original nodes of
      Ranvier. During the next few days proliferating Schwann cells adhered to the
      axons and extended their processes. Clusters of Na+ channels appeared at their
      edges, and as the Schwann cells elongated the distance between these aggregates
      increased. A few clusters associated with neighboring Schwann cells approached
      each other and appeared to coalesce at sites where presumably new nodes of
      Ranvier would be formed. Beyond (3 + 6) days excessive degeneration of the
      transected axons precluded further observations. In the uncut controls, the
      spatio-temporal sequence of Schwann cell proliferation and channel patch
      formation and movement was similar to that described above, although myelin
      formation was somewhat faster than in the cut axons. It is concluded that Na+
      channel aggregation associated with the early stages of remyelination is not
      dependent upon continuous communication of the axon with its cell body and is
      under local control.

PMID- 8567071
TI  - Human epileptic astrocytes exhibit increased gap junction coupling.
AB  - Fluorescence Recovery After Photobleach (FRAP) was used to quantify astrocyte gap
      junction coupling from tissues surgically resected from medically intractable
      epilepsy patients. Mesial temporal lobe cases provided hippocampus, surrounding
      hyperexcitable parahippocampus and normal cortex for culture. Cortical tumor
      cases yielded astrocytoma proper, cortex margins with normal EEG activity, and
      hyperexcitable cortex. Cells isolated from cortex surrounding astrocytomas and
      the parahippocampus surrounding the hippocampus showed an increase in glutamate
      induced Ca2+ oscillations and intercellular Ca2+ waves. Gap-junction coupling was
      more pronounced in cells isolated from hyperexcitable tissue than from normal
      tissues as judged by their faster and more complete fluorescence recovery from
      laser bleach [FRAP]. This data suggests that intractable epilepsy may be
      associated with alterations in glial gap junction coupling.

PMID- 8567072
TI  - Iron-mediated bioactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) in glial cultures.
AB  - Primary cultures of mouse astrocytes were treated with both the monoamine oxidase
      (MAO) A inhibitor, clorgyline, and the MAO B inhibitor, deprenyl, prior to the
      addition of the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP). Production of the 1-methyl-4-phenylpyridinium (MPP+) toxic metabolite was
      reduced to 11%, but not completely blocked, by MAO inhibition. This residual MPP+
      production appeared to be iron-dependent since it was decreased (30 to 50%) by
      iron chelators, i.e., deferoxamine or phenanthroline, and was enhanced (by
      approximately 40%) in the presence of ADP-Fe3+. ADP-Fe3+ also enhanced the
      oxidation of MPTP to MPP+ which occurs in medium without cells. MPP+ formation,
      however, was significantly slower in plain culture medium than in astrocyte
      incubations pretreated with MAO inhibitors, suggesting the involvement of cells
      in these iron-mediated reactions. The data indicate that oxidation via MAO is the
      primary but not the only pathway of MPTP bioactivation and that transition metals
      may contribute to the generation of the toxic MPP+ metabolite in biological
      systems.

PMID- 8567073
TI  - O-2A progenitors of the mouse optic nerve exhibit a developmental pattern of
      antigen expression different from the rat.
AB  - In a previous study we demonstrated that differentiation and development of mouse
      oligodendrocytes is similar to that of the rat after the stage at which O4 is
      acquired. In this present study we compare directly the early differentiation of
      oligodendrocytes in the mouse and rat post natal optic nerve and show that the
      two species differ at the O-2A progenitor and proligodendroblast stages. Mouse
      progenitors show a variety of morphologies compared to the typical bipolar
      appearance in the rat. Many murine cells fail to immunolabel with A2B5, GD3, O4,
      and RmAb, classical markers for rat progenitors, proligodendroblasts, and
      immature oligodendrocytes. We find that these "unlabeled" cells stain for GAP-43
      and that expression of GAP-43 overlaps A2B5 and GD3 in the earlier progenitors
      and O4, RmAb, and O1 in the later proligodendroblasts and immature
      oligodendrocytes. Our data suggest that in the development of the mouse O-2A
      progenitor cells there is a developmental discontinuity between the earlier
      markers such as A2B5 and GD3 and the later marker O4, which can be filled by GAP
      43. We therefore consider that GAP-43 could be used in the mouse, in addition to
      the classical O-2A markers, for the study of the early oligodendrocyte lineage as
      it labels an otherwise undetectable O-2A population.

PMID- 8567074
TI  - A challenging time.

PMID- 8567075
TI  - Thoughts on the future of Medicare.

PMID- 8567076
TI  - How are net health insurance benefits distributed in the employment-related
      insurance market?
AB  - The recent health care reform debate has questioned whether the health insurance
      market effectively pools risks and transfers income across states of health. We
      use data from the 1987 National Medical Expenditure Survey to examine how net
      health insurance benefits are distributed in the employment-related insurance
      market. We find this market to transfer income from those in good health to those
      with health problems and the tax subsidy from employer health insurance
      contributions to be a crucial determinant of the net benefit distribution. To the
      extent society views these transfers as meritorious, our findings suggest caution
      regarding initiatives to limit or eliminate the tax subsidy.

PMID- 8567077
TI  - Premium increases and disenrollment from state risk pools.
AB  - State risk pools exist primarily for persons who want to buy health insurance,
      but are either medically uninsurable or are only able to find a policy at
      considerably higher cost than the rate for a standard insured person. While some
      people enroll in state risk pools for extended periods, many enroll only for a
      limited time. This study analyzes duration of enrollment in eight state risk
      pools using data from 1988 through 1991. A discrete time hazard model provides
      estimates of the relationship between voluntary disenrollment and enrollee and
      plan characteristics. Among other findings, the regressions provide evidence of
      substantial increases in disenrollment in most states in response to premium
      increases that either were implemented by the plan or occurred as enrollees aged
      into higher risk categories.

PMID- 8567078
TI  - Surgeon volume and hospital resource utilization.
AB  - This study examines whether surgeons who perform a particular procedure more
      often incur lower hospital charges and shorter lengths of stay than surgeons with
      less volume. The 43 Pennsylvania hospitals included in the 1991 MedisGroups
      Comparative Hospital Database form the study hospitals. The analysis looks at
      four frequently occurring surgical procedures: cholecystectomy, prostatectomy,
      hysterectomy, and intervertebral disc excision. Regression models are estimated
      separately for total charges, ancillary charges, and length of stay for each
      surgical procedure. The explanatory variable of interest is surgeon volume for
      the specific procedure. Control variables include patient age, sex, admission
      severity of illness, insurance plan, and hospital. For cholecystectomy,
      prostatectomy, and intervertebral disc surgery, we find a significant negative
      association between surgeon volume and both hospital charges and length of stay.
      We find no such volume effect for hysterectomy. The paper discusses management
      and policy implications of these findings.

PMID- 8567079
TI  - Refinements to the Diagnostic Cost Group (DCG) model.
AB  - The Diagnostic Cost Group (DCG) model, originally developed by Ash et al. (1986,
      1989), has been proposed as an alternative to the existing payment system for
      reimbursing Medicare health maintenance organizations, the Adjusted Average Per
      Capita Cost (AAPCC). The DCG model is a linear regression model that uses both
      demographic and diagnostic information to predict total plan payments for health
      care. This paper extends previous work by estimating the model using 1984-85 data
      and by developing a more thorough method for classifying hospitalizations by
      degrees of discretion. It also explores the loss of predictive power resulting
      from not using diagnoses for the most discretionary hospitalizations for
      calculating payments. The paper examines a number of extensions and refinements
      to the basic DCG model.

PMID- 8567080
TI  - Constructing episodes of care from encounter and claims data: some methodological
      issues.
AB  - There is growing agreement that episodes of care methodology provides the most
      effective means of analyzing health care delivery because it organizes health
      care services around the condition or illness for which they were prescribed.
      This paper presents a computerized approach for developing episodes of care from
      encounter and claims data and discusses some methodological issues. We found that
      we could group into five generic types of episodes of care the 31 illnesses that
      incur the majority of expenses for a health maintenance organization. This
      article describes the process for developing these types and summarizes the
      specific criteria defining the episodes of care for the 31 illnesses.

PMID- 8567081
TI  - Bankruptcy risk and state regulation of continuing care retirement communities.
AB  - Continuing care retirement communities (CCRCs) often require substantial
      financial investment from residents, prompting concern about potential losses to
      residents in the event of a CCRC's bankruptcy. State governments have responded
      to this concern with varying levels of regulation. Overall, CCRC bankruptcy rates
      are very low (.3% per year). We found that measures of varying regulation
      stringency had no effect on indicators of CCRCs' financial performance relating
      to bankruptcy risk. CCRCs that offer extensive contracts, including unlimited
      long-term care in addition to housing, have less positive indicators of financial
      strength than other types of CCRCs. When measured by traditional health care
      industry standards of financial strength, CCRCs appear less profitable than other
      types of health care facilities. This raises the question of whether CCRCs can
      continue to attract the needed capital from private markets and because of that,
      suggests that their future growth may be limited.

PMID- 8567082
TI  - Hospital ownership of post-acute care: does it increase access to post-acute care
      services?
AB  - This study examines the relationship of hospital characteristics and access to
      post-acute care (PAC) using a comprehensive database that combines hospital
      characteristics with clinical and demographic information of patients. The data
      was drawn from 52 hospitals in three urban areas--Minneapolis/St. Paul, Houston,
      and Pittsburgh--and 2,572 patients within five diagnosis-related groups (DRGs).
      The analysis found hospital ownership of post-acute care significantly associated
      with use of PAC for patients discharged after hospitalization for stroke and
      chronic obstructive pulmonary disease (COPD). We found few significant hospital
      characteristics influencing use of PAC, but, as expected, for selected DRGs,
      patients were more likely to receive PAC if they were discharged from a hospital
      that either owned post-acute care or served a high proportion of Medicare
      patients. In general, patient characteristics were more consistent predictors of
      post-acute care use across the DRGs studied.

PMID- 8567083
TI  - How adequate are state data to support health reform or monitor health system
      change?
AB  - This article reports on results of a 1994 telephone survey sponsored by the
      Robert Wood Johnson Foundation to obtain better information on state
      policymakers' views of the quality of state-based health data and selected
      information on the actual data available. The findings suggest that state
      policymakers cannot identify easily who and how many are without health insurance
      coverage, nor do they know exactly how much money is spent in the state on health
      care and who spends it. They also cannot ascertain quality or consumers'
      satisfaction with health plans. Funding, lack of comparability across data sets,
      and the reluctance of providers and insurers to submit required data are
      perceived as barriers to improving data. Adopting realistic strategies to
      overcome these barriers may be crucial if states are to assume greater leadership
      in health policy and in monitoring health system performance.

PMID- 8567084
TI  - The ratio of costs to charges: how good a basis for estimating costs?
AB  - This study evaluates the accuracy of costs derived from the ratio of costs to
      charges (RCCs), using costs based on relative value units (RVUs) as the "gold
      standard." We found that RCC-calculated costs were not a good basis for
      determining the costs of individual patients. However, when examining average
      costs per diagnosis-related group (DRG), RCCs performed better. For almost 70% of
      the DRGs, average RCC-calculated costs were within 10% of average RVU-calculated
      costs. RCCs were even more reliable for comparing the relative cost of patients
      in a DRG in one hospital to the average cost of patients in that DRG in a group
      of hospitals. Charges, or an overall hospital RCC (as opposed to the departmental
      RCCs we used in most of our analyses), were not a good basis for determining
      relative hospital costs.

PMID- 8567085
TI  - The present state of occupational and environmental medicine in Italy.

PMID- 8567086
TI  - Use of anthropometric measurements in assessing risk for coronary heart disease:
      a useful tool in worksite health screening?
AB  - The study examined the association between the anthropometric measurements body
      mass index (BMI), waist/hip ratio (WHR), and waist/thigh ratio (WTR) and
      cardiovascular risk factors, and assessed whether a combination of BMI and WHR
      could be used in routine screening of risk for cardiovascular arteriosclerotic
      disease at worksites. The data were obtained from a cross-sectional survey
      designed to assess the nutritional situation, with special reference to
      cardiovascular risk factors. The study population comprised 372 healthy men
      working on platforms in the North Sea. Serum cholesterol, triglyceride,
      fibrinogen, and blood pressure were positively related to the anthropometric
      variables, while high-density lipoprotein (HDL) was inversely related with them.
      The relations remained after adjusting for possible confounders, such as age,
      smoking, physical activity, and an indicator of dietary fat intake. In stepwise
      multiple linear regression models, BMI, WHR, and WTR were positively related to
      serum cholesterol, triglycerides, fibrinogen, diastolic blood pressure, and
      systolic blood pressure, and inversely related to HDL. When controlling for the
      anthropometric variables WHR and WTR, BMI was not independently related to
      fibrinogen and risk score. WHR and WTR were not independently related to systolic
      and diastolic blood pressure, and WTR was in addition not related to
      triglycerides when controlling for BMI. Overall, the anthropometric variables BMI
      and WHR were considered the best predictors for CAD risk when taking several risk
      factors into consideration. A joint variable between BMI and WHR, called "body
      score", constituted the four categories lean, lean android, overweight gynoid,
      and overweight ovoid. This body score was positively associated with levels of
      serum lipids, fibrinogen, and blood pressure, and inversely associated with HDL.
      In stepwise multiple linear regression models, controlling for possible
      confounding variables, body score was positively related to CAD risk. Dividing
      the risk score into tertiles, about 51% of the lean were in the first, while 46%
      of the overweight ovoid were in the third tertile. Those classified as lean
      android or overweight gynoid had about the same distribution, namely between 31%
      and 39% in each tertile if the two categories were combined. These data support
      the hypothesis that BMI, WHR, and WTR are independent predictors for risk factors
      for CAD among oil workers, and that combinations of BMI and WHR are strong enough
      predictors to be useful in routine screening for CAD risk at worksites. Based on
      these findings, supported by data from the literature, a matrix aimed at
      screening for follow-up at worksites is proposed.

PMID- 8567087
TI  - Test chamber exposure of humans to 1,6-hexamethylene diisocyanate and isophorone
      diisocyanate.
AB  - An isocyanate generation apparatus was developed and stable isocyanate
      atmospheres were obtained. At a concentration of 5 micrograms 1,6-hexamethylene
      diisocyanate (HDI) per m3 the precision was found to be 7% (n = 5). Three
      volunteers were each exposed to three different concentrations of HDI (11.9,
      20.5, and 22.1 micrograms/m3) and three concentrations of isophorone diisocyanate
      (IPDI) (12.1, 17.7, and 50.7 micrograms/m3), in an exposure chamber. The duration
      of the exposure was 2 h. Urine and blood samples were collected, and hydrolysed
      under alkaline conditions to the HDI and IPDI corresponding amines, 1,6
      hexamethylene diamine (HDA) and isophorone diamine (IPDA), determined as their
      pentafluoropropionic anhydride amides (HDA-PFPA and IPDA-PFPA). The HDA- and IPDA
      PFPA derivatives were analysed using liquid chromatography mass spectrometry with
      thermospray monitoring negative ions. When working up samples from the exposed
      persons without hydrolysis, no HDA or IPDA was seen. The average urinary
      excretion of the corresponding amine was 39% for HDI and 27% for IPDI. An
      association between the estimated inhaled dose and the total excreted amount was
      seen. The average urinary elimination half-time for HDA was 2.5 h and for IPDA,
      2.8 h. The hydrolysis condition giving the highest yield of HDA and IPDA in urine
      was found to be hydrolysis with 3 M sodium hydroxide during 4 h. No HDA or IPDA
      could be found in hydrolysed plasma (< ca 0.1 micrograms/l).

PMID- 8567088
TI  - Effect of various exposure scenarios on the biological monitoring of organic
      solvents in alveolar air. II. 1,1,1-Trichloroethane and trichloroethylene.
AB  - The purpose of the present study was to investigate the influence of different
      exposure scenarios on the elimination of trichloroethylene (TRI) and 1,1,1
      trichloroethane (1,1,1-TRI) in alveolar air and other biological fluids in human
      volunteers. In addition, it was sought to establish an interactive process
      between experimental data gathering and simulation modeling in an attempt to
      predict the influence of the different scenarios of exposure to TRI and 1,1,1-TRI
      on their respective biological monitoring indices and thus to establish the
      flexibility and validity of simulation models. Two adult male and two adult
      female Caucasian volunteers were exposed by inhalation, in a dynamic controlled
      exposure chamber, to various concentrations of TRI (12.5-25 ppm) or 1,1,1-TRI
      (87.5-175 ppm) in order to establish the influence of exposure concentration,
      duration of exposure, variation of concentration within day, and work load on
      biological exposure indices. The concentrations of unchanged solvents in end
      exhaled air and in blood as well as the urinary excretion of trichloroethanol
      (TCE) and trichloroacetic acid (TCA) were determined. The results show that
      doubling the exposure concentration for both solvents led to a proportional
      increase in the concentrations of unchanged solvents in alveolar air and blood at
      the end of a 7-h exposure period; this proportionality was still observable in
      1,1,1-TRI expired air samples 16 h after the end of the third exposure day. In
      the case of urinary excretion of TCE and TCA, the proportionality between
      excretion and exposure concentration was not as good. It was once again observed
      that the slow excretion of both metabolites leads to progressive cumulation and
      that their urinary determination is subject to considerable interindividual
      variations. After adjustment (lowering) of the exposure concentration to account
      for a prolongation of the duration of exposure (from 8 to 12 h) it was observed
      that the concentrations of TRI or 1,1,1-TRI towards the end of both exposure
      periods are more a reflection of the actual exposure concentration than of the
      exposure duration. Despite important interindividual variations, these adjusted
      and nonadjusted exposures led to almost identical average total urinary excretion
      over 24 h) of TCE and TCA after exposure to 1,1,1-TRI, as was also the case for
      TCE but not for TCA after exposure to TRI. Induced within-day variations in the
      exposure concentration led to corresponding but not proportional changes in
      alveolar air concentrations for both solvents. After exposure to peak
      concentrations there was a lag period before alveolar air concentrations returned
      to prepeak levels. At the end of repeated 10-min periods of physical exercise at
      50 W, alveolar air concentrations of TRI were increased by 50% while those of
      1,1,1-TRI increased by only 12%. After optimization of the physiologically based
      toxicokinetic model parameters with experimental data collected during the first
      exposure scenario, results pertaining to the three other scenarios were
      adequately simulated by the optimized models. Overall, the results of the present
      study suggest that alveolar air solvent concentration is a reliable index of
      exposure to both TRI and 1,1,1-TRI under various experimental exposure scenarios.
      These results also suggest that urinary excretion of TCE and TCA must be
      interpreted with caution when assessing exposure to either solvents. For exposure
      situations likely to be encountered in the workplace, physiologically based
      toxicokinetic modeling appears to be a useful tool both for developing strategies
      of biological monitoring of exposure to volatile organic solvents and for
      predicting alveolar air concentrations under a given set of exposure conditions.

PMID- 8567090
TI  - Cadmium in kidneys in Swedes measured in vivo using X-ray fluorescence analysis.
AB  - An X-ray fluorescence (XRF) technique using plane polarized X-rays for excitation
      was used for in vivo measurements of cadmium in the kidney cortex among non
      occupationally exposed members of the general population in southern Sweden. The
      measured concentrations of cadmium in the kidney cortex of smokers (median 28
      micrograms/g, n = 10) were significantly higher (P = 0.0036) as compared to those
      in non-smokers (median 8 micrograms/g, n = 10), and so were the cadmium
      concentrations in blood and urine. The results show that smoking considerably
      increases the cadmium concentration in the kidney cortex and that smoking is a
      major source of cadmium exposure in the general population of Sweden. Except in
      the presence of very deeply situated kidneys, where the minimum detectable
      concentration is high, non-invasive in vivo XRF analysis of kidney cadmium should
      be a useful tool for evaluating the effects of long-term low-level exposure to
      cadmium and the risk of kidney damage.

PMID- 8567089
TI  - A clinical and immunological study on 92 workers occupationally exposed to
      anhydrides.
AB  - This study aimed at investigating sensitizing and hazardous effects of a new acid
      anhydride, pyromellitic dianhydride (PMDA), in addition to those of phthalic
      anhydride, maleic anhydride and trimellitic anhydride, in a group of 92 exposed
      workers in two German chemical plants. Of the 92 workers, 56 reported work
      related complaints with a predominance of phlegm and dyspnoea in those exposed to
      anhydride dust for less than 1 year. Haemorrhagic rhinitis occurred only after a
      prolonged exposure of more than 15 years. Specific IgE antibodies to anhydride
      HSA conjugates could be detected in 15 exposed subjects, 12 of whom had work
      related symptoms. The IgE-positive group had significantly more impaired lung
      function parameters than the IgE-negative group. The proportion of IgE-positive
      subjects was highest in the groups with dyspnoea (5/18), cough (6/24) and
      rhinitis (11/44) whereas only 1 of 11 workers with haemorrhagic rhinitis had such
      antibodies. A follow-up study of 23 affected workers was performed after 10
      months to assess clinical symptoms, lung function and IgE antibody levels. This
      follow-up study showed the absence of obstructive ventilation patterns in three
      out of six subjects in addition to cessation of symptoms in most initially
      affected workers who were no longer exposed. On the other hand, 14 workers under
      continuous exposure had comparable pathological findings on re-examination. Our
      results confirm that anhydrides including the lesser known PMDA, behave as
      respiratory irritants and as immediate-type sensitizers. They predominantly
      induced reversible symptoms in workers whose exposure stopped after a working
      period of about 0.7 years. Abnormal lung function parameters normalized in nearly
      50% of these subjects.

PMID- 8567091
TI  - Early reaction type allergies and diseases of the respiratory passages in
      employees from persulphate production.
AB  - The prevalence of positive skin-prick test reactions ammonium persulphate and
      potassium persulphate (1% and 5% solutions) was tested in a cross-sectional study
      on 52 employees of a company producing persulphates after a case of "persulphate
      asthma" was observed. A random test of 13 persons without occupational exposure
      to persulphates served as controls; among them all the skin-prick test reactions
      were negative. Eight company employees showed a positive skin-prick test reaction
      to at least one of the persulphate solutions tested. Employees showed lower lung
      function results with a positive prick test reaction than did employees with a
      negative result. The positive skin-prick reactions correspond well to the
      anamnestic data and indicate a possible relationship to obstructive ventilation
      disorders. The results therefore suggest an IgE-induced, allergic pathomechanism
      of "persulphate asthma" triggered by persulphates.

PMID- 8567092
TI  - Effect of tobacco consumption on the function of male accessory sex glands.
AB  - The function of accessory sex glands in 29 tobacco smokers, 25 tobacco chewers
      and 30 non-users of tobacco was investigated by determining the ejaculate
      contents of various glandular markers: N-acetyl amino sugar and total phosphate
      (seminal vesicles) zinc and acid phosphatase (prostate gland), and alpha-1,4
      glucosidase (epididymis). Both vesicular and prostatic parameters were reduced
      significantly in smokers compared with non-users of tobacco, whereas these
      parameters were unchanged in tobacco chewers. This difference may be due either
      to the difference in constitution of xenobiotics emitted as a result of burning
      tobacco, or to differences in the pharmacokinetics of the two forms of tobacco
      consumption. The activity of alpha-1,4-glucosidase was significantly lowered in
      both types of tobacco users. It is concluded that use of tobacco, especially by
      smoking, impairs the secretory function of accessory sex glands in man.

PMID- 8567093
TI  - Testosterone enanthate at a dose of 200 mg/week decreases HDL-cholesterol levels
      in healthy men.
AB  - The concept that androgen alone can provide an effective male contraceptive has
      been tested in a multicentre, multiphase trial by the World Health Organization.
      Results from this trial showed that an ester of testosterone, testosterone
      enanthate (TE), administered at a dose of 200 mg/week, has a very high
      contraceptive efficacy, and suggested that, at least in some populations,
      androgen alone might provide a viable option for the control of male fertility.
      It has been claimed that testosterone represents one of the gender-related risk
      factors for coronary artery disease (CAD) in men. Epidemiological and
      interventional studies have failed to establish a convincing relationship between
      testosterone and high density lipoprotein cholesterol (HDL-C). Therefore, there
      is concern about possible negative effects on lipoprotein asset of an androgen
      alone male contraceptive. In this study we analysed the effects of long-term (12
      months) administration of TE (200 mg/week) in normal healthy men. Blood samples
      (six men > 10 h fast = Group 1; 30 men > 4 h fast = Group 2) were drawn from 36
      men, monthly before the beginning of the injections (control), every 3 months
      throughout the study period (treatment), and 1 month after stopping TE injections
      (recovery). Total cholesterol (chol), triglycerides, HDL-C and LDL-C levels were
      measured in these samples. Biochemical parameters were also monitored. TE
      administration induced a significant decrease (15-20%) in HDL-C levels that was
      of comparable magnitude in men from both groups (fasting and non-fasting) and
      occurred regardless of basal HDL-C levels. No statistically significant effect on
      other lipoproteins was detected. Considering all men together, HDL-C levels were
      decreased in 78% of the men by month 3, 83% by month 6, 94% by month 9 and 97% by
      month 12 of treatment. In all men the HDL-C decrease was reversible within 1
      month of stopping TE administration. It is concluded that: (1) injection of 200
      mg TE/week causes a 15-20% decrease in HDL-C in normal men with no effect on
      other lipoproteins, (2) the suppressive effect of TE is maintained throughout the
      1-year-injection period, and a direct relationship between the duration of TE
      administration and the proportion of men showing decreased HDL-C levels, was
      observed. (3) The HDL-C decrease was reversible within 1 month of stopping TE
      administration. These data will be important in designing further studies on male
      contraception, and in interpreting the relationship between testosterone levels,
      HDL-C levels and potential cardiovascular risk.

PMID- 8567094
TI  - Organ-specific binding system for beta-galactosidase in the male reproductive
      tract.
AB  - This study reports on the binding of beta-galactosidase obtained from different
      organs of the rat urogenital tract to membranes of these organs. Homologous and
      cross binding saturation assays indicated that: (1) high-affinity sites that
      recognize fructose-6-phosphate derivates (FPR) are present in spermatozoa from
      the rete testis, epididymal membranes and testes, although the latter may reflect
      binding to testicular spermatozoa; (2) the membranes of the other organs studied
      do not have FPR; (3) the FPR of the epididymis does not recognize enzymes
      purified from other organs of the reproductive tract. These results suggest that
      the FPR-binding system belongs to a peculiar transport route that permits
      maturing spermatozoa to acquire hydrolytic enzymes secreted by the epididymal
      epithelium. In the epididymis and seminal vesicles more than 50% of the enzymatic
      activity of beta-galactosidase was recovered in cytosol, suggesting that the
      enzyme is located mainly in the secretory fluid of these organs.

PMID- 8567095
TI  - Comparison of the effects of chlormadinone acetate-pellet implantation and
      orchidectomy on benign prostatic hypertrophy in the dog.
AB  - Five beagles out of 11 dogs aged 7-10 years with benign prostatic hypertrophy
      (BPH) were implanted subcutaneously with pellets of the synthetic anti-androgen
      chlormadinone acetate (CMA) at a dose of 10 mg/kg bodyweight. The remaining six
      dogs (one beagle and five mongrel dogs) underwent bilateral orchidectomy. Changes
      in prostatic volume, histological findings in the prostate and the testis, and
      peripheral plasma levels of LH, testosterone and oestradiol-17 beta (E2) were
      assessed up until 24 and 4 weeks after CMA-implantation and orchidectomy,
      respectively. Measurements of the size of the prostate and biopsies of the
      prostate were performed by laparotomy. Mean prostatic volume had decreased to 71%
      and 41%, respectively, of its pretreatment volume, by 4 weeks after CMA
      implantation and orchidectomy, and was 49% and 47%, respectively, of pretreatment
      volume at 12 and 24 weeks after CMA-implantation. The clinical signs of BPH, e.g.
      haematuria, resolved within 2 weeks after either treatment. When the prostate was
      examined histologically 4 weeks after either treatment, hardly any evidence of
      active secretion (e.g. glandular epithelium projecting markedly into the lumen),
      was observed in CMA-implanted dogs, alveolar diameter and height of the glandular
      epithelium had decreased markedly and the glandular lumen had become very small
      in the orchidectomized dogs. By 12 weeks after CMA-implantation, degenerative and
      atrophic glands were observed in the prostate nearly the same as at 4 weeks after
      orchidectomy. In the testis the number of germ cells in the seminiferous tubules
      decreased markedly after CMA-implantation. The mean level of plasma LH at 4 weeks
      after orchidectomy had increased to 14.9 ng/ml, twice the value before operation.
      The mean levels of plasma testosterone and E2 at 4 weeks after CMA-implantation
      had decreased to 0.7 ng/ml and 9 pg/ml from 1.5 ng/ml and 15 pg/ml, the values
      before treatment, respectively. CMA-implantation resulted in poor semen quality.
      The results indicate that CMA-implantation at a dose of 10 mg/kg results in the
      same prostate-shrinking effect as orchidectomy.

PMID- 8567096
TI  - In-situ quantification of stage-specific apoptosis in the rat seminiferous
      epithelium: effects of short-term experimental cryptorchidism.
AB  - Two techniques have been combined for quantification of apoptotic germ cells in
      defined stages of the cycle of the seminiferous epithelium: the improved
      transillumination method and nonradioactive in-situ end-labelling of DNA (ISEL).
      Segments of rat seminiferous tubules were squashed between a microscope slide and
      coverslip, and the stage identified under a phase-contrast microscope. After
      fixation, apoptotic cells were detected by ISEL and scored per 1 mm tubule. In
      the normal testis apoptotic cells were found in all stages, the highest frequency
      occurring in stages XII-XIV (19 cells/mm). In short-term (24 and 48 h)
      experimentally cryptorchid testes, a significant increase in number of apoptotic
      germ cells was evident in all stages, except for VI and VIII. Apoptosis of germ
      cells was confirmed by electrophoresis of radioactively labelled DNA from stages
      VII-VIII and XIII-I. It is proposed that apoptosis is a means of eliminating the
      most sensitive germ cells after short-term experimental cryptorchidism.

PMID- 8567097
TI  - Characterization of beta-N-acetylglucosaminidase from human epididymis.
AB  - beta-N-acetylglucosaminidase (NAG) activity in human epididymal fluid was
      separated into two forms (I and II) after HPLC-hydrophobic interaction
      chromatography. Both forms exhibited maximal activity at a pH of around 4.5 and
      had a molecular weight of 125 kD when determined by Superose-HPLC. After
      incubation at 50 degrees C, form I retained only 30% of its activity while form
      II retained 90% activity. When analysed by non-denaturing electrophoresis, form I
      displayed higher electrophoretic mobility than did form II. These features
      indicate that the I and II isoforms found in the human epididymis are the A and B
      forms present in other tissues. NAG activity was measured in the fluid obtained
      form the different epididymal regions of 13 different samples. An average four
      fold increase in activity between the proximal caput and distal corpus was found.
      The contribution of each isoform to the total activity was studied. The proximal
      caput found to be rich in the A isoform (59%), whereas the B form was predominant
      in the distal corpus (65%). Human spermatozoa contain membrane-associated NAG
      activity with an isoform distribution similar to that found in cauda epididymal
      fluid (CEP, 80% B). Finally, enzyme activity in CEP was two-fold greater than in
      seminal plasma. Taken together these results suggest that NAG may become
      associated with human spermatozoa during epididymal transit.

PMID- 8567098
TI  - Androgens in seminal plasma: markers of the surface epithelium of the male
      reproductive tract.
AB  - Androgens in seminal plasma have been investigated in relation to other markers
      of the male reproductive system. Testosterone and dihydrotestosterone (DHT) were
      measured by radioimmunoassay after paper chromatography in 104 semen samples.
      Concentrations of testosterone and DHT were significantly lower in samples from
      patients with abnormal sperm characteristics than in men with normozoospermia.
      Both testosterone and DHT were correlated significantly with sperm concentration
      (r = 0.40, p < 0.001; r = 0.41, p < 0.001, respectively), motile sperm
      concentration (r = 0.35, p < 0.01; r = 0.35, p < 0.01) and ATP concentration (r =
      0.59, p < 0.001; r = 0.45, p < 0.001). In addition, the total amounts of
      testosterone and DHT were correlated with total activity of alpha-glucosidase (r
      = 0.49, p < 0.001; r = 0.58, p < 0.01), and gamma-glutamyltransferase (r = 0.49,
      p < 0.001; r = 0.48, p < 0.001) in seminal plasma. Transferrin (Tf) concentration
      in seminal plasma was significantly lower in samples without spermatozoa, and
      total Tf content was lower in oligozoospermic samples (p < 0.05). Testosterone
      and DHT were correlated positively with Tf levels in seminal plasma (r = 0.48, p
      < 0.0001; r = 0.78, p < 0.0001 respectively). Testosterone, DHT and Tf in seminal
      plasma were higher in the first than in the second fraction of split ejaculates,
      and DHT, but not testosterone, increased significantly in each of six patients
      treated with tamoxifen. Testosterone, DHT, and Tf in seminal plasma were not
      correlated with serum concentrations of LH, FSH, testosterone or prolactin, but
      the DHT : T ratio in seminal plasma was correlated with serum LH (r = 0.36, p <
      0.05). It is concluded that the concentration of androgens in seminal plasma is
      related predominantly to the activity of the seminiferous epithelium and, to a
      lesser extent, to the function of the accessory sex glands.

PMID- 8567099
TI  - Hepatitis C virus infection in dialysis and clinical nephrology.
AB  - Hepatitis C Virus (HCV), a single-strand RNA virus, has recently been cloned and
      sequenced. It causes nearly all cases of non-A non-B post-transfusion hepatitis
      (NANBH), and is responsible for most of the community-acquired NANBH.
      Considerable progress has been made in characterizing HCV and understanding the
      prevalence, transmission, and natural history of HCV infection.

PMID- 8567100
TI  - On-line estimation and prediction of urea kinetics during hemodialysis: a
      simulation approach.
AB  - A new method for the on-line estimation of urea kinetic parameters from blood
      urea concentration (BUN) continuously measured during a dialysis session is
      proposed. The method, based on the variable-volume double-pool model, is
      evaluated through a simulation approach in order to easily consider a large set
      of well-controlled test conditions. The model is characterized by six parameters,
      knowledge of which enables early prediction of the end dialysis urea
      concentration and the dose of dialysis. The sensitivity of the model predicted
      BUN with respect to the parameters was first analyzed to investigate which can be
      reliably estimated from blood urea measurements taken at a suitable rate. This
      analysis showed that the model predicted BUN is highly sensitive to the initial
      blood urea concentration and to the dialyzer clearance, normalized with respect
      to the total initial distribution volume, while it is scarcely influenced by the
      normalized ultrafiltration and urea generation rates. The new on-line estimation
      technique keeps these two last parameters constant and takes advantage of an
      original analytic solution of the second order urea kinetics. The results of the
      estimation process on realistic simulated data showed that the proposed method
      provides early and reliable estimates of the normalized clearance and of the end
      dialysis concentration. The transcellular mass transfer coefficient and the intra
      extra cellular volume ratio can also be estimated, although with less accuracy.
      Moreover, it was shown that the use of the single-pool model, instead of the
      double-pool one, provides systematic errors on the estimates.

PMID- 8567101
TI  - Serious renal disease in Egypt.
AB  - We studied serious renal disease in Egypt by registering all 155 patients coming
      to the nephrology service at the University of Cairo during a period of 62 days
      in 1993. The patients presented with severe uremic symptoms. Admission creatinine
      and urea levels were high, 804 mumol/l and 64 mmol/l. Fifteen percent of the
      patients died; 115 underwent dialysis. Sixty patients presented with chronic
      renal failure; 53 with acute renal failure, but 24 of these were later found to
      have end-stage renal failure. Of 29 patients with true acute renal failure, 11
      (38%) had pre-renal failure and 7 (24%) post-renal failure. Twenty-one patients
      were followed up after transplantation and chronic dialysis, another 17 had
      nephrotic syndrome, 3 hypertension, and one had asymptomatic urinary
      abnormalities. The most common specific etiology for chronic end-stage renal
      failure was diabetes mellitus type II in the older patients; second most common
      was Schistosoma in the younger ones. Most diabetic patients came from the city.
      All but one Schistosoma patient came from rural Egypt. In the 22 patients who
      underwent renal biopsy the most common diagnosis was mesangio capillary
      glomerulonephritis. The prevalence of acute renal failure, particularly
      iatrogenic-toxic, is increasing.

PMID- 8567102
TI  - Leaching and corrosion of polyvinyl chloride (PVC) tubes in a dialysis water
      distribution system.
AB  - PVC tubes, from the dialysis water distribution system of a 14 and a 7 year old
      plant, were analysed by scanner electron microscopy (SEM) and X-ray microanalysis
      (EDAX). Results showed that the leaching of material occurs depending on time of
      use. The phenomenon does not modify the chemical composition of the material.
      Results suggest that PVC alterations, induced by time, could support bacterial
      proliferation thus reducing the quality of dialysate.

PMID- 8567103
TI  - In vivo comparative study of two lactobionate based solutions for prolonged heart
      preservation.
AB  - The duration of safe heart preservation must be improved. Using a heterotopic
      heart transplantation model, we compared in vivo the recovery of rabbits hearts
      preserved with a K+Lactobionate based fluid (UW: University of Wisconsin
      solution) or with a Na+Lactobionate based fluid. In the "preservation" group,
      hearts were cold stored (4 degrees C) for 6 hours with UW (n = 9) or
      Na+Lactobionate solution (n = 9). In the "transplantation" group, cold storage
      was followed by 3 hours of reperfusion (UW: n = 8, Na+Lactobionate solution: n =
      7). Functional recovery, adenine nucleotide pool, circulating blood cardiac
      enzymes, circulating blood and tissue malondialdehyde (MDA) were measured. Left
      ventricular end-diastolic and developed pressures at different preload levels
      were better after preservation with UW than with Na+Lactobionate solution (p <
      0.05). Also with UW, adenosine diphosphate and total adenine nucleotide content
      were significantly higher than with Na+Lactobionate solution (p < 0.05) whereas
      adenosine triphosphate, monophosphate and energy charges were similar. Cardiac
      enzymes and tissue MDA were similar with UW and Na+Lactobionate solution. In
      circulating blood, MDA was not detected. These results enhance the superiority of
      UW solution over a Na+Lactobionate based solution for long term heart
      preservation.

PMID- 8567104
TI  - Hydraulic refinement of an intraarterial microaxial blood pump.
AB  - Intravascularly operating microaxial pumps have been introduced clinically
      proving to be useful tools for cardiac assist. However, a number of complications
      have been reported in literature associated with the extra-corporeal motor and
      the flexible drive shaft cable. In this paper, a new pump concept is presented
      which has been mechanically and hydraulically refined during the developing
      process. The drive shaft cable has been replaced by a proximally integrated micro
      electric motor and an extra-corporeal power supply. The conduit between pump and
      power supply consists of only an electrical power cable within the catheter
      resulting in a device which is indifferent to kinking and small curvature radii.
      Anticipated insertion difficulties, as a result of a large outer pump diameter,
      led to a two-step approach with an initial 6,4mm pump version and a secondary
      5,4mm version. Both pumps meet the hydraulic requirement of at least 2.5l/min at
      a differential pressure of 80-100 mmHg. The hydraulic refinements necessary to
      achieve the anticipated goal are based on ongoing hydrodynamic studies of the
      flow inside the pumps. Flow visualization on a 10:1 scale model as well as on 1:1
      scale pumps have yielded significant improvements in the overall hydraulic
      performance of the pumps. One example of this iterative developing process by
      means of geometrical changes on the basis of flow visualization is illustrated
      for the 6.4mm pump.

PMID- 8567105
TI  - LDL-apheresis in two patients with extremely elevated lipoprotein (a) levels.
AB  - Hyperlipidemia and elevated lipoprotein (a) [Lp(a)] levels have been linked to
      the development and progression of premature atherosclerosis. Two male caucasian
      patients (36 and 42 years old) with heterozygous familial hypercholesterolemia
      and extremely elevated Lp(a) concentrations, resistant to diet regimen and lipid
      lowering drugs, were treated with LDL-apheresis for 55 months (liposorber system,
      Kaneka, Japan) and 15 months (immunoadsorption system, special Lp(a) columns,
      Lipopak, Pocard, Russia). Lp(a) dropped on average by 50%, total cholesterol by
      27%, LDL-cholesterol by 42%, triglycerides by 43% and the fibrinogen
      concentration by 16%. Prior to treatment, both patients had suffered three
      myocardial infarctions. Four and six coronary angiographies with two and four
      percutaneous transluminal angioplasties (PTCA) were necessary. Since the
      treatment with LDL-apheresis neither myocardial infarctions nor cardiac
      complaints have been observed, and both patients have reported better
      performance. Available data suggest that LDL-apheresis may be effective in the
      treatment of patients with extremely high Lp(a) concentration.

PMID- 8567106
TI  - Validation of a differential PCR and an ELISA procedure in studying HER-2/neu
      status in breast cancer.
AB  - HER-2/neu oncogene status and total cellular p185HER-2 content were
      simultaneously analyzed in 415 invasive breast-cancer specimens by differential
      PCR and ELISA respectively. Mathematical analysis of the data led us to establish
      a cut-off value of 1.7 for the ratio between the intensity of the HER-2/neu gene
      band and the reference gene band, to consider the HER-2/neu gene amplified, and
      of 260 fmol/mg protein, to consider p185HER-2 over-expressed. Of the 415 tumors
      studied, 15% showed a diverse degree of HER-2/neu gene amplification. Of these
      tumors, 87% showed over-expression of the p185HER-2. Of the remaining 352
      specimens that did not display HER-2/neu gene amplification, 97% showed no
      p185HER-2 over-expression (p < 0.0001). In 40 selected samples with a p185HER-2
      level lower than 260 fmol/mg protein, the degree of p185HER-2 phosphorylation was
      very low or undetectable. Conversely, 38 of 46 selected tumors with a p185HER-2
      level higher than 260 fmol/mg protein exhibited a considerable degree of p185HER
      2 phosphorylation (p < 0.0001). Our data suggest that: (i) differential PCR and
      ELISA, which are relatively simple procedures, give similar information on HER
      2/neu status in breast cancer; and (ii) given the large series analyzed, the
      cutoff values established can be considered as safe values for determining
      whether, in a given tumor, the HER-2/neu oncogene is amplified or p185HER-2 is
      over-expressed.

PMID- 8567107
TI  - Influence of the major histocompatibility complex on age at onset of chronic
      lymphoid leukaemia.
AB  - The major histocompatibility complex is one of the interactive factors in the
      multifactorial model of carcinogenesis. Its main influence in experimental models
      is on the age at onset of malignancies. We have previously shown a similar effect
      of homozygosity for HLA-DR53 in CML. In the present study, we investigated 79
      patients with CLL and 329 local controls from Germany. In addition to full
      serotyping, all patients and 116 of controls were also typed by HLA-DRB PCR
      analysis. The homozygosity rates for DR53 in patients under and over the median
      age (60 years) were 18.6% and 2.9%, respectively (p = 0.03). Eight of the 9
      homozygous patients were under the median age. The sex ratio in the DR53
      homozygous group was reversed in favour of females. The homozygosity rates for
      DR53 were different in the overall groups of patients and controls, yielding a
      relative risk (RR) of 2.4 (p = 0.03). This association was stronger in the early
      onset group compared to age-matched controls (RR = 4.4; p = 0.008) and for
      females with an early onset compared to age- and sex-matched controls (RR = 17.9;
      p = 0.0008). The simultaneous occurrence of the alleles of the haplotype A2B62DR4
      showed a strong association with CLL (RR = 4.1; p = 0.002). This was probably the
      reason behind the association with HLA-DRB1*0401 (RR = 2.4; p = 0.009). Compared
      to the accelerating effect of HLA-DR53, HLA-DR52 showed a significant delaying
      effect on the onset of CLL. These findings confirmed the influence of the HLA
      complex on the development of another leukaemia.

PMID- 8567108
TI  - Intake of selected micronutrients and the risk of breast cancer.
AB  - To investigate the relation between selected micronutrients and breast cancer
      risk, we conducted a case-control study of breast cancer between June 1991 and
      April 1994 in 6 Italian areas. The study included 2569 women admitted to the
      major teaching and general hospitals of the study areas with histologically
      confirmed incident breast cancer and 2588 control women with no history of
      cancer, who were admitted to hospitals in the same catchment areas for acute, non
      neoplastic, nongynecological conditions unrelated to hormonal or digestive tract
      diseases or to long-term modifications of the diet. Dietary habits, including
      alcoholic beverage consumption, were investigated using a validated food
      frequency questionnaire, including 78 foods or food groups, several types of
      alcoholic beverages, some "fat intake pattern" questions and some open sections
      for foods consumed frequently by the subject and not reported in the
      questionnaire. To control for potential confounding factors, several multiple
      logistic regression models were used. When major correlates, energy intake and
      the mutual confounding effect of the various micronutrients were taken into
      account, beta-carotene, vitamin E and calcium showed a significant inverse
      association with breast cancer risk. The estimated odds ratios of the 5th
      quintile compared to the lowest one were 0.84 for beta-carotene, 0.75 for vitamin
      E and 0.81 for calcium. No significant association emerged for retinol, vitamin
      C, thiamin, riboflavin, iron and potassium. Our results suggest that a diet rich
      in several micronutrients, particularly beta-carotene, vitamin E and calcium, may
      be protective against breast cancer.

PMID- 8567109
TI  - European randomized study of screening for prostate cancer--the Rotterdam pilot
      studies.
AB  - Five randomized pilot studies of screening for prostate cancer (PC) have been
      conducted in the area of Rotterdam from 1991 to 1994. The purpose of these
      studies was to establish the feasibility of a randomized screening protocol with
      PC mortality as the major end point in The Netherlands and at a European level.
      All procedures related to recruitment of participants, to application of the
      screening tests and to data collection were evaluated. Men (7,200) aged 55-74
      years were invited through the Rotterdam Population Registry. The recruitment
      rate over the 5 pilot studies averaged 38.2% (2,747 men). Recruitment procedures
      proved to be relevant for establishing higher participation rates (invitation and
      consent by mail). The screening tests were well accepted and tolerated. The
      general population-based character of the sample was confirmed by studying
      symptoms of prostatic disease in participants and in men who refused
      participation. Data based on one PSA serum determination, rectal examination and
      transrectal ultrasonography are presented; 204/1,403 men (14.5%) had a positive
      screening result by either test combination and underwent biopsy. Forty-nine
      cancers were found in 1,403 men (3.5%); 65% of prostate cancers (17/26)
      identified in men who eventually underwent radical prostatectomy proved to be
      locally confined. From the pilot studies, we conclude that a large contribution
      to a European Randomized Study of Screening for Prostate Cancer (ERSPC) can be
      made by recruiting about 40,000 men in the area of Rotterdam. The preliminary
      data suggest that after confirmation of the present data during the first years
      in the European study, DRE and TRUS can be withheld depending on the PSA result
      in a large proportion of the screening population.

PMID- 8567110
TI  - Modulation of immune parameters in patients with metastatic renal-cell cancer
      receiving combination immunotherapy (IL-2, IFN alpha and autologous IL-2
      activated lymphocytes).
AB  - We treated 72 patients with metastatic renal-cell cancer according to 2 protocols
      consisting of two 5-week induction cycles of continuous i.v. high-dose
      interleukin-2 (IL-2), i.m. interferon-alpha (IFN alpha) and ex vivo IL-2
      activated lymphocytes, followed for patients with stable disease (SD), partial
      response (PR) or complete response (CR) by four 4-week maintenance cycles of IL-2
      and IFN alpha. Protocol 2 (55 patients) differed from protocol 1 (17 patients) in
      (i) the addition of IFN alpha to the first IL-2 infusions in both induction
      cycles; (ii) the use of Teceleukin IL-2, reconstituted with carrier protein,
      instead of Proleukin IL-2 without carrier protein. We classified 23 patients with
      CR and PR as responders (4 in protocol 1 and 19 in protocol 2) and 45 patients
      with SD and progressive disease as non-responders. Prior to immunotherapy,
      patients entered into protocol 2 already had higher IFN gamma serum
      concentrations, higher peripheral blood CD56-,3+ and CD8-,4+ lymphocyte numbers
      and lower NKK562 activity than those entered into protocol 1. These differences
      persisted during and after immunotherapy. In line with these observations, ex
      vivo IL-2-activated lymphocytes had larger proportions of CD56-,3+ and CD8-,4+
      lymphocytes and lower NKK562 activity in protocol 2 than in protocol 1. Higher IL
      2 serum concentrations were reached during the IL-2 infusion in protocol 2 than
      in protocol 1. In addition, the immunomodulation in protocol 2 was stronger than
      in protocol 1 as indicated by higher TNF alpha serum concentrations and a more
      pronounced eosinophilia. Differences between responders and non-responders
      treated according to the 2 protocols were not significant, except for the total
      number of lymphocytes obtained by apheresis, which was higher in responders than
      in non-responders.

PMID- 8567111
TI  - Cytoplasmic localization of EGF receptor in papillary thyroid carcinomas:
      association with the 150-kDa receptor form.
AB  - We have previously reported that papillary thyroid carcinomas show an increased
      expression of EGFR mRNA and protein, compared to non-tumorous thyroid tissue.
      EGFR immunoreactivity was localized to the cytoplasm as well as to the membrane
      in papillary carcinomas. To further study EGFR protein expression in human
      thyroid tissue, we performed immunohistochemistry and Western blots of 64
      different thyroid tissue samples from 36 patients, including 23 patients with
      papillary carcinomas. Two receptor forms were identified in human thyroid tissue,
      a 170-kDa and a 150-kDa form. The 150-kDa receptor form was more pronounced in
      papillary carcinomas, while the 170-kDa receptor was the dominant form in non
      malignant thyroid tissues. Predominance of the 150-kDa EGFR in the tumour samples
      was associated with strong cytoplasmic EGFR staining. EGFR gene structure,
      protein synthesis and maturation were found to be normal. Immunoprecipitation and
      Western-blot analysis of EGFR from the human thyroid SGHTL-34 cells after
      increased ligand concentration showed a decreased amount of the mature 170-kDa
      receptor and a relative increase in the 150-kDa receptor. We have previously
      demonstrated the presence of a TGF-alpha-EGFR autocrine loop in papillary thyroid
      carcinomas, and this may explain increased receptor turnover and accumulation of
      a cytoplasmic degradation product.

PMID- 8567112
TI  - Over-expression of hepatocyte growth factor in human Kaposi's sarcoma.
AB  - Kaposi's sarcoma is a highly vascularized multifocal tumor which frequently
      appears as a complication of HIV infection. It has been suggested that a disorder
      in the cytokine network may contribute to the development of the disease. We
      examined the expression of several cytokines in human sporadic Kaposi's-sarcoma
      specimens, as well as in spindle cells cultured from human lesions, and
      consistently found high levels of expression of hepatocyte growth factor (HGF).
      In addition, human lesion-derived spindle cells synthesize and secrete
      biologically active hepatocyte growth factor and express the hepatocyte-growth
      factor receptor (c-MET). Moreover, elevated levels of transforming growth factor
      beta 1 (TGF beta 1) mRNA were found in lesions of human sporadic Kaposi's sarcoma
      and in lesion-derived spindle cells which also over-express urokinase. Since HGF,
      TGF beta 1 and urokinase are all involved in capillary-vessel organization,
      dysregulation of these interacting agents may play a role in the initiation
      and/or progression of Kaposi's sarcoma, stimulating the growth of spindle cells
      and recruiting endothelial cells into the lesion.

PMID- 8567113
TI  - Apoptosis occurs more frequently in metastatic foci than in primary lesions of
      human colorectal carcinomas: analysis by terminal-deoxynucleotidyl-transferase
      mediated dUTP-biotin nick end labeling.
AB  - We examined the occurrence of apoptotic cell death in 15 advanced colorectal
      carcinomas with lymph-node and/or liver metastases by terminal-deoxynucleotidyl
      transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL). TUNEL-positive
      cells were used to quantify the apoptotic index (AI: percentage of TUNEL-positive
      cells in carcinomatous cells). Similarly, Ki-67-positive cells were used to
      quantify Ki-67 labeling (KI: percentage of Ki-67-positive cells in carcinomatous
      cells) as a proliferative index. The mean AIs of primary colorectal carcinomas,
      lymph-node and liver metastases were 3.5%, 5.6% and 6.2% respectively. There was
      a significant group difference between primary carcinomas and lymph-node or liver
      metastases. The mean KIs of primary colorectal carcinomas, lymph-node and liver
      metastases were 51.8%, 60.1% and 61.7% respectively. There was a significant
      group difference between primary carcinomas and lymph-node or liver metastases.
      In addition, there was a close positive relationship between the AI and MI per
      specimen. There was no apparent correlation between AI or MI and the expression
      of nuclear p53 of cancer cells. These results suggested that cell proliferation
      and loss (apoptosis) were more frequent in metastatic foci than in primary
      lesions, and that apoptosis might reflect not only cell loss but also the
      proliferative activity of human colorectal carcinomas.

PMID- 8567114
TI  - Phorbol-ester-stimulated human lymphoid cell lines produce a plasminogen
      activator modulator inducing cell-bound urokinase-type plasminogen activator in
      malignant tumor cell lines.
AB  - The importance of cell-associated plasminogen activation in tumor invasion and
      metastasis is becoming increasingly evident. To clarify the modulators of cell
      associated plasminogen activation in malignant states, we have recently
      established an assay system utilizing endogenous plasminogen activators on the
      cell surface. In the present study using the assay system, we found that the
      conditioned medium from phorbol 12-myristate 13-acetate (PMA)-stimulated human
      lymphoid cell lines, HUT 78 and Raji, strongly enhanced plasminogen activator
      (PA) activity on the surface of human malignant tumor cell lines (WI-38 VAI3 2RA,
      A431, A549 and HT-1080). The enhancing effect was inhibited by the addition of
      actinomycin D. By gel filtration, the active substances in PMA-stimulated HUT 78-
      and Raji-conditioned media were eluted in similar fractions corresponding to
      molecular weights of 60 to 80 kDa. The active substance was heat-labile. The
      enhanced PA activities were completely inhibited by anti-urokinase-type
      plasminogen activator (uPA) IgG. Moreover, the active substance was found to
      increase in cell-bound uPA antigen. These findings suggest that a population of
      activated lymphocytes produces a plasminogen activator modulator that induces uPA
      on the surface of malignant tumor cells.

PMID- 8567115
TI  - Effects of tyrosine kinase inhibitors on the proliferation of human breast cancer
      cell lines and proteins important in the ras signaling pathway.
AB  - Breast cancers frequently over-express a number of growth factor receptors. In
      addition, elevated src family kinase activity is present in a percentage of these
      neoplasms and has been implicated in signal transduction in these cells.
      Therefore, inhibiting tyrosine kinase activity is a potential approach for
      treating these tumors. Utilizing the SKBR3 and MCF-7 breast cancer cell lines, we
      evaluated the effects of broadly targeting growth factor receptor and cytoplasmic
      tyrosine kinases with tyrosine kinase inhibitors (herbimycin A and genistein) to
      inhibit proliferation. We also evaluated these inhibitor's effects on proteins
      that regulate ras function, which is a convergence point for signaling through
      both src family kinases and a number of growth factor receptors with tyrosine
      kinase activity (e.g., epidermal growth factor and erbB-2 receptors). We
      specifically evaluated whether these compounds affected 2 recently discovered
      proteins involved in controlling ras function: Shc, which is tyrosine
      phosphorylated by src and activated growth factor receptors, and Grb-2, which
      mediates signal transduction from activated growth factor receptors through ras.
      We evaluated their effects on tyrosine phosphorylation of Shc, binding of Grb-2
      to Shc and MAP kinase activity. Both cell lines were inhibited in a dose
      dependent manner by each compound. This was accompanied by decreased Shc tyrosine
      phosphorylation, Shc's association with Grb-2 and MAP kinase activity. Thus,
      tyrosine kinase inhibitors can inhibit proliferation of breast cancer cells,
      accompanied by inhibition of signal transduction steps potentially mediated
      through ras. Tyrosine kinase inhibitors might, therefore, be useful for the
      treatment of breast cancer.

PMID- 8567116
TI  - Lu-ECAM-1-mediated adhesion of melanoma cells to endothelium under conditions of
      flow.
AB  - Lu-ECAM-1 is a lung-derived, venular endothelial cell adhesion molecule. It
      promotes the selective adhesion of lung-metastatic B16-F10 melanoma cells to
      endothelium under static conditions and mediates colonization of the lungs by the
      same tumor cells. To test whether Lu-ECAM-1 by itself is sufficient to cause
      vascular arrest of B16-F10 cells, we measured here under conditions of flow tumor
      cell adhesion to endothelia that express different amounts of Lu-ECAM-1 on their
      surfaces. At physiological shear stresses, adhesion of B16-F10 melanoma cells to
      endothelia correlates positively with the amount of Lu-ECAM-1 expression on the
      endothelial cell surface and inversely with the level of the applied shear
      stress. Tumor cell trajectories are biphasic; i.e., B16-F10 melanoma cells
      initially move along the endothelial surface with a velocity similar to the
      theoretical velocity, then arrest within a fraction of a second. Arrest is
      permanent for most B16-F10 melanoma cells at all shear stresses tested. Tumor
      cells never engaged in a rolling motion prior to arrest. Masking of the Lu-ECAM-1
      ligand on the surface of B16-F10 melanoma cells with soluble Lu-ECAM-1 impedes
      arrest of tumor cells on the surface of the test endothelium. Purified Lu-ECAM-1
      also mediates B16-F10 arrest, but arrest is mostly transient at shear stresses of
      0.59 dynes/cm2 and higher, implying adhesion by single receptor/ligand bonds. Our
      data suggest that Lu-ECAM-1 plays a critical role in the recognition and initial
      arrest of murine melanoma cells in lung venules.

PMID- 8567117
TI  - Kaposi's sarcoma in childhood: an analysis of 100 cases from Uganda and
      relationship to HIV infection.
AB  - We report 100 cases of Kaposi's sarcoma (KS) in children under 15 years of age
      treated at the Uganda Cancer Institute in the 6-year period 1989-1994. The
      incidence of childhood KS has risen more than 40-fold in the era of AIDS, and 78%
      of 63 cases tested were seropositive for HIV-1. There were 63 boys and 37 girls.
      The median age was 4 years and the median age of onset was 33 months. Tumour
      distribution was lymphadenopathic and muco-cutaneous, with 2 major patterns:
      pattern I, oro-facial dominant (79%); and pattern II, inguinal-genital dominant
      (13%). A newly described herpes-like virus is implicated as the cause of KS
      (KSHV), and DNA sequences of this virus were present in all of 8 childhood cases
      tested. If KSHV is a direct cause of KS, this tumour distribution in children
      suggests mucosal routes of virus entry, possibly during birth or breast feeding.
      The dramatic increase of childhood KS implies that the prevalence of causative
      factors is rising in Uganda.

PMID- 8567118
TI  - Tumor-cell vaccination induces tumor dormancy in a murine model of B-cell
      leukemia/lymphoma (BCL1).
AB  - Immunity to murine B-cell leukemia/lymphoma (BCL1) induced by multiple injections
      with irradiated tumor cells, prevented leukemia development in primary and
      adoptive transfer recipients despite long-lasting persistence of residual tumor
      cells. Detection of dormant BCL1 cells was carried out by PCR analysis using the
      VH-rearranged DNA sequence as a BCL1 clonal marker. Dormant tumor cells were
      detected > 250 days following immunity induction in 40% of spleens from healthy
      immune mice having no detectable symptoms of disease. Tumor dormancy was not
      abrogated by adoptive transfer of BCL1-containing splenocytes into syngeneic
      recipients, indicating that cell-mediated anti-tumor immunity contributes to
      maintenance of the tumor dormant state and prevents renewed tumor-cell growth.
      Splenocytes but not sera from immune mice conferred specific radiosensitive
      protection from a lethal dose of BCL1 cells included in cell mixtures transferred
      to secondary recipients. A therapeutic effect of transferred immune splenocytes
      was shown in BCL1-bearing mice, which remained disease-free for > 200 days after
      inoculation; nevertheless, dormant BCL1 cells were detected by PCR analysis in
      some of the surviving mice. Our results suggest that an efficient tumor-cell
      vaccine can lead to induction of tumor dormancy that can be maintained by a cell
      derived mechanism for a long period of time.

PMID- 8567119
TI  - High level of MT-MMP expression is associated with invasiveness of cervical
      cancer cells.
AB  - MMP-2 (gelatinase A) has been associated with the invasive potential of many
      cancer cells both in vitro and in vivo. It is now becoming clear that the
      activation of this enzyme might be a key step in tumor invasion. This activation
      process has been shown to be a membrane-associated pathway inducible by various
      agents such as collagen type I, concanavalin A or TGF-beta, but its physiological
      regulation is still largely unresolved. MT-MMP was recently discovered and
      described as a potential gelatinase-A activator. In the present study, we
      investigated the expression of MT-MMP (membrane-type metalloproteinase) in
      cervical cancer cells both in vitro and in vivo. Comparing several in vitro
      transformed cervical cell lines, previously shown to display different invasive
      potentials, our results showed that the ability of cells to overexpress MT-MMP
      mRNA following ConA induction correlated with their ability to activate
      gelatinase A and with a highly invasive behavior. Moreover, using
      immunohistochemistry and in situ hybridization, we found a higher level of MT-MMP
      expression in invasive cervical carcinoma and lymph node metastases compared to
      its expression in non-invasive CIN III lesions. Our in vivo observations also
      clearly demonstrated a cooperation between stromal and tumor cells for the
      production of MT-MMP. Taken together, our results clearly correlated high level
      MT-MMP expression with invasiveness, and thus suggested that MT-MMP might play a
      crucial role in cervical tumor invasion.

PMID- 8567120
TI  - Experimental radiotherapy of receptor-positive human prostate adenocarcinoma with
      188Re-RC-160, a directly-radiolabeled somatostatin analogue.
AB  - The therapeutic potential of the somatostatin analogue RC-160 radiolabeled with
      188Re was evaluated in nude mice bearing xenografts of human prostate
      adenocarcinoma. 188Re-RC-160 was selectively retained in both DU-145 and PC-3
      tumors following direct intra-tumor injection at all time points examined (2, 6
      and 24 hr post-injection). Unbound 188Re-RC-160 was rapidly excreted via the
      hepatobiliary system and, with the exception of the gastrointestinal tract, very
      little normal organ uptake was found at any time point examined. Negative control
      compounds, 188Re-perrhenate and 188Re-mercaptoacetyl-triglycine (188Re-MAG3),
      were essentially washed out of the tumor by 6 hr post-injection and were rapidly
      excreted through the kidneys. 131I-RC-160, used as reference compound, had a
      biodistribution in tumor-bearing animals similar to that of 188Re-RC-160. In PC-3
      xenografts, 188Re-RC-160 gave a dose-dependent therapeutic response (stasis or
      regression) even in animals with relatively large tumor masses (greater than 600
      mm3), whereas the macro-aggregated form of 188Re-RC-160 did not. Long-term
      studies with 188Re-RC-160 demonstrated a protracted reduction of tumor volume and
      a positive effect on animal survival. Neither RC-160 by itself nor a 188Re
      labeled peptide, unrelated to somatostatin (PA-22-2, a laminin peptide),
      demonstrated the reduction in tumor mass observed with 188Re-RC-160. 188Re-RC-160
      shows potential as a new clinical agent for treatment of somatostatin-receptor
      positive cancers.

PMID- 8567121
TI  - The murine Fc-gamma (Fc gamma) receptor type II B1 is a tumorigenicity-enhancing
      factor in polyoma-virus-transformed 3T3 cells.
AB  - The murine receptor for the Fc portion of IgG is a molecule expressed by cells of
      the immune system. This study suggests the hypothesis that Fc gamma receptor type
      II B I (Fc gamma RIIB I) functions as a progression-enhancing factor when
      expressed ectopically on non-lymphoid tumor cells. It has been shown previously
      that BALB/c 3T3 cells transformed in vitro with polyoma virus (PyV) do not
      express Fc gamma RII but acquire the expression of this receptor following an in
      vivo passage in syngeneic mice. The specific Fc gamma RII transcript present in
      tumor cells was identified in this report as Fc gamma RIIB I (BI). In order to
      determine whether or not the ectopically expressed Fc gamma RII plays a role in
      the progression of these transformed cells, PyV-transformed 3T3 cells were
      transfected with BI-cDNA. The BI transfected cells were tested for their ability
      to form local tumors in syngeneic mice, as compared to transfected cells which
      express the co-transfecting neomycine resistance (neores) DNA alone or together
      with the lacZ gene. Fc gamma RIIB I expressors exhibited a significantly higher
      tumorigenic phenotype than FcR-negative controls, though both types of cells
      exhibited the same growth curve in vitro. The ability of Fc gamma RIIB I to act
      as a potentially tumorgenicity-enhancing factor was also demonstrated as Fc gamma
      RII was expressed by tumor cells, originating from inoculated Fc gamma RIIB I
      transfected cells, or from inoculation of a mixture of receptor-positive and 
      negative cells. B I-expressing cells dominated the tumor-cell population over non
      expressors. This dominance strengthened the hypothesis that FcR plays a role in
      tumor progression in vivo.

PMID- 8567122
TI  - Overlapping phenotypes of multidrug resistance among panels of human cancer-cell
      lines.
AB  - In addition to P-glycoprotein (Pgp), 2 proteins related to multidrug resistance
      (MDR) have recently been described. The Multidrug-Resistance-associated protein
      (MRP) is one of the ATP-binding-cassette (ABC) transporters. The Lung-Resistance
      Protein (LRP) is the major component of human vaults, which are newly described
      cellular organelles and thought to mediate intracellular transport processes.
      Using immunocytochemical methods, we have examined the expression of MRP and LRP
      among panels of human cancer-cell lines not selected for drug resistance which
      have been previously characterized for expression of Pgp, and in vitro response
      to a variety of anti-cancer drugs. Expression of MRP and LRP was observed in
      47/55 (87%) and 46/59 (78%) cell lines, respectively. Statistically significant
      correlations were observed between expression of each of these 3 proteins and in
      vitro sensitivity to at least one drug classically associated with MDR. LRP
      showed the greatest individual predictive value, which also applied to several
      non-classical MDR drugs. Co-expression of 2-3 MDR-related proteins was observed
      in 64% of the lines and was, in general, associated with high relative levels of
      drug resistance. Previously identified "classic" MDR lines as well as "pan
      resistant" lines concurrently expressed all 3 MDR-related proteins. Some highly
      drug-resistant cell lines without detectable MDRI/Pgp were found to express
      relatively high levels of MRP and LRP. The high prevalence of MRP and LRP
      expression observed in this large set of cell lines, which have not been
      subjected to laboratory drug selection, suggests that MDR mechanisms associated
      with these proteins may be widespread in human malignancies. Moreover, the
      overlapping of these more recently recognized MDR phenotypes with Pgp-type MDR
      results in a complex phenotype, the understanding of which may be of importance
      in the development of new drugs and design of clinical treatment protocols,
      particularly those seeking to employ strategies to reverse the MDR phenotype.

PMID- 8567123
TI  - Modulation of MR-visible mobile lipid levels by cell culture conditions and
      correlations with chemotactic response.
AB  - A transformed murine fibroblast cell line has been used to assess which criteria
      govern the appearance of a lipid pool that is mobile on the MR time scale. A high
      resolution proton MR signal arising from neutral lipids, including triglyceride
      and cholesteryl esters, has previously been associated with membrane events in
      stimulated, transformed and malignant cells. We report that the attenuation of
      cellular proliferation by confluence or low pH caused significant increases in MR
      visible lipid and that the lipid signal could be amplified at high density by the
      removal of serum. A significant decrease in chemotactic response accompanied the
      culture of cells at high density, but chemotactic response was not generally
      linked to alteration of the lipid signal. The appearance of the signal was also
      not correlated with the proportion of cells in any phase of the cell cycle.
      Significant changes in the MR-visible pools of the lipid metabolites choline,
      phosphocholine and glycerophosphocholine were measured under the culture
      conditions employed with 2D MRS and suggest that MR-visible lipid may arise from
      the catabolism of phospholipids.

PMID- 8567124
TI  - Photodynamic eradication of amelanotic melanoma of the hamster with fast acting
      photosensitizers.
AB  - Three porphycenes with fast pharmacokinetics were tested for their ability to
      photosensitize amelanotic hamster melanoma A-Mel-3 at short time intervals after
      injection. Laser light irradiation was performed at the time of maximal
      photosensitizer level in tumor tissue. Photodynamic therapy as short as 5 min
      after injection led to complete local tumor remission at a dosage of 1.4 mumol/kg
      for the porphycene CBPn. In comparison, Photofrin required 8.4 mumol/kg for local
      tumor remission in 5 of 6 animals with 24 hr accumulation time after injection.
      We propose a swift photodynamic protocol which can compete favorably with
      conventional techniques of tumor treatment.

PMID- 8567125
TI  - Frequency and histological appearance of adenomas in multiple intestinal
      neoplasia mice are unaffected by severe combined immunodeficiency (scid)
      mutation.
AB  - Well-characterized murine mutations are powerful analytical tools for the genetic
      analysis of tumorigenesis. We crossed the multiple intestinal neoplasia (Min)
      allele of adenomatous polyposis coli (Apc), which produces a profound pre
      disposition to intestinal neoplasia, with the severe combined immunodeficiency
      (scid) mutation, which causes defective double-strand DNA repair and severe
      immunodeficiency, on the common C57BL/6J genetic background to assay for any
      combined effect on intestinal tumorigenesis. Several phenotypic traits were
      exacerbated in an apparently additive manner in the double mutant mice, including
      reduced immunoglobulin levels, reduced body weight and increased morbidity.
      However, quantitation and histological evaluation of polyp phenotype indicated
      that these mutations did not interact to affect either polyp frequency or
      progression. Thus, neither genome instability nor lack of immunosurveillance
      conferred by scid contributes to intestinal polyps in this model.

PMID- 8567126
TI  - Expression pattern of the cell adhesion molecules. E-cadherin, P-cadherin and
      alpha 6 beta 4 intergrin is altered in pre-malignant skin tumors of p53-deficient
      mice.
AB  - Expression of the cell adhesion molecules E-cadherin, P-cadherin and alpha 6 beta
      4 integrin and of the keratin K13 has been analyzed in chemically induced benign
      skin papillomas with genetically pre-determined risks for malignant conversion.
      It has been previously shown that papillomas induced in mice lacking both alleles
      of the p53 gene have a much higher rate of malignant conversion than those
      induced in wild-type and heterozygous p53 mice. Alterations in the expression
      pattern of the E-cadherin molecule, including focal loss at cell-cell contacts
      and heterogeneous distribution in the differentiated layers, were found in about
      70% of the p53 null papillomas. In contrast, all of the wild-type and over 85% of
      the heterozygous p53 papillomas exhibited an expression pattern of E-cadherin
      indistinguishable from that of normal epidermis. Alterations in P-cadherin
      expression were also detected in the p53 null papillomas: aberrant suprabasal
      localization and heterogeneous distribution were observed more frequently than in
      heterozygous and wild-type p53 papillomas. The alpha 6 beta 4 integrin showed
      suprabasal expression in more than 70% of the papillomas derived from either wild
      type, heterozygous or homozygous p53 null mice. Surprisingly, the extent of the
      suprabasal localization of alpha 6 beta 4 decreased in the p53 null papillomas.
      Aberrant keratin K13 expression was also detected in the majority of cases of all
      p53 genotypes, but again there was a clear decrease in expression levels in the
      p53 null papillomas. These alterations were also associated with keratinocytic
      atypia, which increased significantly in the p53 null papillomas. Changes in
      these parameters were particularly evident during malignant conversion in
      invasive regions of one progressing p53 null papilloma. Our results indicate the
      existence of dynamic changes in the expression pattern of the 3 cell adhesion
      molecules analyzed and identify down-regulation of E-cadherin as an early step in
      malignant conversion.

PMID- 8567127
TI  - Non-enzymatic and enzymatic activation of mitomycin C: identification of a unique
      cytosolic activity.
AB  - Mitomycin C (MMC), an alkylating anti-tumor agent, was activated by non-enzymatic
      and enzymatic mechanisms leading to DNA binding and adduct formation. However, it
      was enzymatically, not non-enzymatically, activated MMC which induced inter
      strand DNA cross-linking, a major determinant of cell death. The enzymatic
      activation of MMC was catalyzed by microsomal NADPH:cytochrome P450 reductase
      (P450 reductase) and cytosolic enzyme activities. Human P450 reductase,
      transiently expressed from its cDNA in the COSI cells, metabolically activated
      MMC to generate 9 specific MMC-DNA adducts and induced inter-strand DNA cross
      linking. Co-chromatography of the MMC-DNA adducts generated by P450 reductase and
      sodium borohydride in separate experiments indicated that MMC was metabolized by
      P450 reductase to produce 2,7-diaminomitosenes that exhibited binding to
      deoxyguanosine. Several experiments indicated that cytosolic enzymes which
      catalyzed reductive activation of MMC and DNA cross-linking included
      NAD(P)H:quinone oxidoreductaseI (NQOI or DT diaphorase) when present in extremely
      high concentrations and a unique cytosolic activity. The unique cytosolic
      activity was present in several mammalian cells and mouse colon and liver but
      absent in mouse kidney. The unique activity had properties of a diaphorase but
      was distinct from NQOI because of a lack of correlation between NQOI (2,6
      dichlorophenolindophenol reduction) activity and the amount of MMC-reductive
      activation leading to DNA cross-linking. This activity was also distinct from
      xanthine oxidoreductase and NADH-cytochrome b5 reductase, 2 other enzymes that
      catalyze metabolic activation of MMC, because the unique activity was not
      inhibited by allopurinol (an inhibitor of xanthine oxidoreductase) and its
      activity was the same with NADH and NADPH (cytochrome b5 reductase is specific to
      NADH).

PMID- 8567128
TI  - Patterns of HTLV-I infection among family members of patients with adult T-cell
      leukemia/lymphoma and HTLV-I associated myelopathy/tropical spastic paraparesis.

PMID- 8567129
TI  - Critical steps in total knee arthroplasty. A method of analyzing operative
      procedures.
AB  - We have analyzed the operation of knee arthroplasty using the Whiteside Mark II
      prosthesis, and found that it could be broken down into 42 steps, some of which
      are more important than others and can be considered as critical. We have
      identified 4 criteria to evaluate a critical step: 1) it must be necessary to
      complete the procedure, 2) it must take a significantly longer time to perform
      than other steps, 3) it must be revised significantly more frequently than other
      steps and 4) it must take significantly longer to revise than other steps. Two
      steps have been found to which all 4 criteria applied, namely placement of the
      femoral cutting jig and the first femoral saw cuts.

PMID- 8567130
TI  - [Treatment of posterior cruciate ligament rupture and recent knee dislocations by
      olecranisation of the patella without surgical repair].
AB  - Olecranisation of the patella was described and first used by Grammont (1984) to
      maintain reduction of the knee joint after posterior cruciate repair and
      reconstruction. Since 1985 we used this technique in 18 acute posterior ruptures
      and knee dislocations which did not undergo surgery. Knee laxity is assessed
      under general anaesthesia with radiographic control. A 4 or 5 mm. Steinmann pin
      is introduced medially at the top of the patella and drilled vertically through
      the bone to continue behind the patella tendon. After reduction of the posterior
      drawer, the pin is passed into the anterior part of the tibia. Full mobility
      between 0 degrees and 90 degrees is maintained. Physiotherapy started immediately
      and early weight bearing is allowed with a posterior splint. Olecranisation
      prevents posterior subluxation of the tibia and gives an anterior tibial
      subluxation force which is minor in flexion but major in extension. We followed
      up our patients for 1 to 8 years. The latest testing with radiographs demonstrate
      posterior drawer but all patients report good results. Early physiotherapy avoids
      stiffness, amyotrophy, and reflex sympathetic dystrophy. Olecranisation appears
      to give similar results more quickly and with fewer complications than P. C. L.
      surgery.

PMID- 8567131
TI  - Popliteal cysts and associated disorders of the knee. Critical review with MR
      imaging.
AB  - We have studied retrospectively the epidemiological features of popliteal cysts
      in adults and the incidence of associated intra-articular disorders in a series
      of 1001 patients undergoing magnetic resonance imaging who had been randomly
      referred to our institution. Images of popliteal cysts were seen in 4.7% of this
      group which is lower than in other studies with different imaging techniques. A
      communication with the joint was invariably found. The cysts were associated with
      one, or more, disorders detected by MRI in 94%. The commonest lesions were
      meniscal (83%), frequently involving the posterior horn of the medial meniscus,
      chondral (43%), and anterior cruciate ligament tears. Our data suggest that intra
      articular disorders may play an important role in the pathogenesis of popliteal
      cysts in adults.

PMID- 8567132
TI  - Unicameral bone cyst of the patella. A case report.
AB  - We present a case of a simple bone cyst in the patella in a women of 33 years. We
      were only able to find one similar case in the literature.

PMID- 8567133
TI  - The relation between osteoporosis of the spine and osteoarthritis of the knee. A
      study using dual energy X-ray absorptiometry and radiographs.
AB  - We investigated the relation between osteoporosis of the spine and osteoarthritis
      of the knee using dual energy X-ray absorptiometry of the lumbar spine to measure
      bone mineral density and radiographs of the knee in 82 randomly selected females
      (mean age 77.5 years). Radiographs of the knee were divided into a normal and
      severe group. The bone mineral density of the severe group was significantly more
      than that of the normal group.

PMID- 8567134
TI  - A modified open palm technique for Dupuytren's disease. Short and long term
      results in 54 patients.
AB  - Fifty-four patients with Dupuytren's disease were operated on using transverse
      and Bruner incisions, leaving the transverse palmar and digital wounds open. The
      mean follow up was 6.6 years (minimum 5 years). The mean percentage correction of
      the overall fixed flexion deformity was 71%. The incidence of recurrence and
      extension of the disease were similar to other series of limited aponeurectomy.
      However, the postoperative complications were very much lower and the method is
      particularly suitable for patients over 50 years of age.

PMID- 8567135
TI  - Abduction contracture of the deltoid muscle in children.
AB  - Deltoid contracture is usually congenital and affects the intermediate part of
      the muscle. Fibrosis occurring in these fibres produces the contracture. Six
      patients are reported. Recovery occurred after resection of the fibrotic band.

PMID- 8567136
TI  - Intervertebral disc calcification in childhood.
AB  - Nine children with calcified intervertebral discs are described. Seven were boys
      and 2 were girls. The average age at diagnosis was 8.6 years (range 5 to 14
      years). Follow up was from 2 to 10 years. Only one child gave a history of
      trauma. In all twelve discs were involved with more than one disc being affected
      in 2 children; there were 7 in the cervical spine, 4 in the thoracic and one in
      the lumbar spine. Every child with cervical calcification had an acute onset with
      pain and limited movement, and disappeared during the following months. The
      calcified discs in the thoracic and lumbar regions did not cause symptoms and did
      not change. Calcification of cervical discs is self-limiting and has an excellent
      prognosis.

PMID- 8567137
TI  - Reduced neck movement after operations for cervical spondylotic myelopathy.
AB  - Complaints resulting from reduced neck movements were investigated in 50 patients
      who had operations for cervical spondylotic myelopathy. Seventy per cent had
      difficulty in performing 11 basic movements of daily living. Lateral bending or
      rotation were more difficult than flexion and extension. To look backwards was
      the most difficult movement. Complaints were highest among those in whom more
      than three levels of fusion had been carried out.

PMID- 8567138
TI  - Revision arthroplasty with an isoelastic uncemented femoral stem.
AB  - We carried out 102 hip revision arthroplasties using an uncemented isoelastic
      femoral stem on 92 patients between 1985 and 1989. The proximal femoral bone
      stock had deteriorated in 45%. Eleven patients died during the mean follow up of
      5.7 years. The femoral component has been revised again for loosening in 13, for
      infection in 5 and for dislocation in 3. Radiographs of 70 hips showed incipient
      migration at 3 months in 20, and at the time of review 27 hips had migrated 5 mm
      or more. Nine stems had migrated more than 8 mm and were judged to be loose.
      There were 11 fractures before operation and 15 during operation; they all
      healed. Slight cortical hypertrophy of not more than 2 mm was present in most
      cases. Three patients (4 hips) were excluded because of severe systemic illness.
      Of the remaining 66 hips, the clinical outcome was excellent in 18%, good in 50%,
      fair in 26% and poor in 6%. The isoelastic stem is associated with poor primary
      fixation which is indicated by early subsidence. The results, with a total
      failure rate of 33%, are unsatisfactory and the isoelastic femoral stem used in
      this series cannot be recommended for revision operations.

PMID- 8567139
TI  - Uncemented porous-coated anatomic total hip replacement in Chinese patients.
AB  - Primary uncemented Porous-Coated Anatomic total hip replacement was carried out
      in 72 hips in 62 Chinese patients. Their average age was 50 years and the average
      follow up was 3 1/2 years. The most common diagnosis was avascular necrosis. The
      average preoperative Harris score of 36.3 points improved to 83.2 at the last
      follow up. The pain score improved from 13.7 out of 44 to an average of 42. Seven
      of 8 hips with thigh pain had an inadequately fitting stem which had subsided.
      Only one cup was revised because of a technical error and one femoral component
      for loosening. Uncemented Porous-Coated Anatomic total hip replacement gave good
      early results in Chinese patients.

PMID- 8567140
TI  - The incidence of vertebral body metastases.
AB  - Over 10 years, 842 consecutive autopsies on patients dying from a malignant
      neoplasm were evaluated microscopically to determine the incidence of spinal and
      skeletal metastases. Vertebral wedging, sclerosis and areas of osteolysis were
      defined as features of spinal metastases. The incidence was 30.6%, 65% of which
      arose from lung, breast or lymphoma and myeloma. The frequency of extraspinal
      metastases was 9.8% with 66% arising from the lung, liver, lymphoma or myeloma;
      they were mainly situated in the ribs, skull and clavicle.

PMID- 8567141
TI  - Ultrasonographic monitoring of the effects of preoperative chemotherapy in
      osteosarcoma and Ewing's sarcoma.
AB  - This study evaluates ultrasonography as a method of monitoring the effect of
      preoperative chemotherapy on two types of tumour. Changes in the size of tumours
      of 15 patients (13 osteosarcoma, 2 extraosseous Ewing's sarcoma) were monitored
      by this method, and the results compared with the histological examination of the
      resected specimens. Six patients in whom the tumour size increased towards the
      end of chemotherapy showed in inadequate histological response, whereas 6 of the
      7 patients in whom the tumour decreased in size had a good histological response.
      Ultrasonography is of value as it can indicate the effect of preoperative
      chemotherapy on sarcoma by monitoring the size of the tumour, and it is simple
      and cheap to use.

PMID- 8567142
TI  - Diffuse spinal leptomeningeal metastases from prostatic cancer. A case report.
AB  - A patient with a spinal form of diffuse metastatic leptomeningeal carcinoma from
      prostatic cancer is reported. The clinical manifestations and diagnosis are
      discussed, and the literature reviewed.

PMID- 8567143
TI  - Differentiation of vertebral osteomyelitis and tuberculous spondylitis by
      magnetic resonance imaging.
AB  - Twenty patients with vertebral osteomyelitis and 18 with tuberculous spondylitis
      were investigated by magnetic resonance imaging to identify the distinguishing
      features. The number of vertebral bodies involved was less in vertebral
      osteomyelitis than in tuberculous spondylitis, and the paravertebral abscesses
      were smaller. The magnetic resonance intensity of the involved vertebral bodies
      was more homogeneous in vertebral osteomyelitis than in tuberculous spondylitis.
      Rim enhancement with Gadolinium-DTPA was less frequent in vertebral
      osteomyelitis. The differentiation of the two conditions by MRI was helpful in
      establishing the correct diagnosis of the infection.

PMID- 8567144
TI  - Retrofascial nontuberculous psoas abscess.
AB  - Psoas abscess is usually associated with tuberculous spondylitis, but also occurs
      in relation to inflammatory bowel disease. We present 17 cases of primary
      pyogenic psoas abscess seen during a 10 year period at the King Fahd Hospital, Al
      Khobar. There were 13 males and 4 females with a mean age of 24.9 years (range
      one to 55 years). Five patients had sickle cell disease. The average delay in
      presentation was 4.5 weeks (range 2 to 9 weeks). Pyrexia and a painful hip with a
      flexion deformity were the most obvious signs. The sedimentation rate and white
      cell count were markedly raised in every case. Staphylococci were cultured in 10
      and anaerobic streptococci, salmonella and E coli in 2 each. Ultrasonography, CT
      and MR imaging were used to confirm the diagnosis. Early recognition and drainage
      are important to ensure a rapid recovery.

PMID- 8567145
TI  - Severe kyphotic deformity in tuberculosis of the spine.
AB  - Almost 3% of cases of tuberculosis of the spine develop a severe kyphotic
      deformity. The patients at risk are those who developed the disease under the age
      of 10 years, who had involvement of three or more vertebral bodies and had
      lesions between C7 to L1. A severe kyphosis is more than a cosmetic disfigurement
      because nearly all such patients develop cardiopulmonary dysfunction, painful
      impingement between ribs and pelvis and compression of the spinal cord with
      paraplegia at an average of 10 years after the onset of the disease. Correction
      of the established deformity is difficult and dangerous. Anterior transposition
      of the cord does not always result in permanent neurological recovery, so it is
      imperative to diagnose and treat the condition either before bony destruction has
      occurred or when it is in an early phase. Those patients who are at risk of
      developing a severe deformity should be treated by posterior fusion of the spine.

PMID- 8567146
TI  - Pectus carinatum successfully treated with bracing--a case report.

PMID- 8567147
TI  - The clinical and radiological results of revision of low friction arthroplasty in
      the elderly.
AB  - We assessed 130 patients (138 hips) who were more than 70 years old at the time
      of revision arthroplasty and had a minimum follow-up of 4 years. The average
      follow-up was for 7 years 3 months. The clinical results were excellent or
      satisfactory in 95.6% of the cases. Systemic complications developed
      postoperatively in 47 patients (34.1%). Radiographically, 95.6% had a well-fixed,
      stable stem while 91.3% had a stable socket. Seven hips (5.1%) required re
      revision. Analysis revealed a 96.5% survival of the arthroplasty at 8 years.

PMID- 8567148
TI  - [Arthroscopy of the wrist: diagnostic and therapeutic contribution].
AB  - An arthroscopy was carried out on 23 wrist joints following trauma. There were 11
      women and 12 men with a mean age of 36 years, and they were followed up for an
      average of 33 months. Statistically significant differences were observed in the
      radiolunate and scapho-lunate angles between the injured and normal sides.
      Arthroscopy detected 72 ligament tears, an average of 3 per wrist, compared with
      1 per wrist demonstrated by arthrography. However the findings of the two
      investigations did not correlate, indicating that both are worth undertaking.
      Chondromalacia was seen in 10 wrists, mostly in the radiocarpal and mid carpal
      joints. On the basis of the findings at arthroscopy, conservative treatment was
      followed in 60% of the patients and the investigation was of great help in
      planning operation in the remainder.

PMID- 8567149
TI  - Periprosthetic bone mineral density of the distal femur after total knee
      arthroplasty.
AB  - Evaluation of the bone mineral density (BMD) was performed in the distal femur
      around the femoral component of a total knee prosthesis. A total of 48 females
      were enrolled for this study, including 14 with osteoarthritis of one knee
      undergoing total knee arthroplasty (TKA) with an Osteonics prosthesis, 14 with
      osteoarthritis of one knee undergoing TKA with a Whiteside prosthesis, and 20 age
      matched normal controls. The BMDs of both knees were measured before operation,
      and then at 3, 6 and 12 months after operation. The preliminary results
      demonstrate a significant progressive decrease of BMD in the distal femur of the
      operated knees after TKA, whereas the BMD of the non-operated knees remains
      stable. The ratio of BMD between the operated femur and the non-operated femur
      began to decrease 6 months after operation, and was most obvious at the end of
      the first year (ranging from 7% to 27%). Further investigation is essential to
      determine the clinical significance of this loss of periprosthetic bone.

PMID- 8567150
TI  - Fractioned drilling--a technique for wedge osteotomy of the knee.
AB  - High tibial wedge osteotomies are often followed by transient neurological
      complications. From a retrospective study of 132 patients it appears that the
      incidence of this troublesome complication can be reduced after osteotomy with
      external fixation by using a technique of making consecutive drill holes of
      increasing diameter followed by osteoclasis. This reduction of neurological
      complications was most marked when a less extensive surgical approach was used.

PMID- 8567151
TI  - Patellar reconstruction of the condyles in giant cell tumours of the knee.
AB  - Reconstruction of a resected femoral or tibial condyle using the ipsilateral
      patella as an autogenous graft is better than conventional resection arthrodesis.
      Seven cases are reported with a follow up of from 3 to 6 years. Consolidation of
      the graft and fair stability were obtained. The range of movement was more than
      90 degrees in 5 out of the 7 cases.

PMID- 8567152
TI  - Fracture of the styloid process of the temporal bone. A case report.
AB  - A case of fracture of the styloid process of the temporal bone (Eagle's syndrome)
      is reported. The differential diagnosis is discussed.

PMID- 8567153
TI  - Pain drawing in the evaluation of low back pain.
AB  - Pain drawings were obtained from three groups of patients: 51 with lumbar disc
      herniation; 55 with lumbar stenosis, and 42 with benign low back pain. On grid
      assessment, patients with disc herniation and stenosis who complained of
      radiating pain or intermittent claudication had a significantly larger number of
      grids for the extremities than those with benign low back pain. In studies of the
      relation between the characteristics of the pain drawing and the outcome of
      treatment, most patients with 19 grids or less, or a score of 3 points or less,
      had a satisfactory outcome. Those with more grids or a higher score tended to be
      unsatisfactory. Pain drawing permits differentiation of the three patterns of
      pain and is useful for predicting the outcome of treatment.

PMID- 8567154
TI  - Hernia through iliac crest defects. A report of four cases.
AB  - Herniation of abdominal contents through the donor site in the ilium occurred in
      5% of a series of 59 bone grafts. Four patients had this condition at a 7 year
      follow up, and 2 were repaired with synthetic mesh. Age, gender, obesity and
      surgical technique are important causative factors. Preventive measures are
      proposed which have been successful during the past 3 years.

PMID- 8567155
TI  - Iatrogenic pectus carinatum. A case report.
AB  - A boy underwent cardiac surgery when he was 27 months old; prior to that his
      anterior chest wall had been normal. He later developed a progressive pectus
      carinatum deformity. Thoracic surgeons are cautioned to be mindful of the sternal
      and costal growth plates in any surgical approach to intrathoracic structures.
      Special care is needed when such deformities are corrected in children and
      adolescents.

PMID- 8567156
TI  - Can amputation be avoided in local recurrence after limb salvage for high grade
      osteosarcoma? A case report and a review of the literature.
AB  - We report a case of local recurrence after a limb salvage procedure for high
      grade osteosarcoma. We carried out a second salvage operation because the lesion
      was small, there were no distant metastases, the patient had initially responded
      to chemotherapy and was able to receive more drugs. She is still alive, well and
      free of disease more than 6 years after the second operation, and 9 years after
      the diagnosis was made. Amputation is not always needed for every case of
      recurrence.

PMID- 8567157
TI  - Consolidation of massive bone allografts in limb-preserving operations for bone
      tumours.
AB  - This study analysed the influence of several factors affecting the consolidation
      time of 83 massive bone allografts in 79 patients with malignant bone tumours:
      osteosarcoma 57; Ewing's sarcoma 8; malignant fibrous histiocytoma 3;
      chondrosarcoma 4; fibrosarcoma 5; and giant cell tumours 2. The mean age of the
      patients was 19 years and the mean length of the allografts was 18 cm. The
      minimum follow up was for 12 months. The mean consolidation time for metaphyseal
      and diaphyseal osteotomies was 6.5 and 16 months respectively. Fifteen diaphyseal
      osteotomies required autologous cancellous grafting. There were 8 allograft
      fractures after consolidation. The following factors which might influence
      consolidation were analysed: age of the host and donor; allograft length and
      site; type of osteotomy and osteosynthesis; intra-arterial and systemic
      chemotherapy; intraoperative and external radio-therapy. In diaphyseal
      osteotomies there were statistically significant differences in consolidation
      time with the use of systemic chemotherapy, external radiotherapy and the
      recipient's age.

PMID- 8567158
TI  - Surgical treatment of extra-abdominal desmoid tumours (aggressive fibromatoses).
AB  - Extra-abdominal desmoid tumours (EADT) are benign lesions but difficult to cure
      because of their infiltrative nature and tendency to recur. Among many treatments
      recommended in the past, wide excision has been successful, even in difficult
      cases. We have analyzed retrospectively 41 cases of histologically confirmed
      EADTs. A total of 98 operations were performed on these patients: 29 wide
      excisions on 22 patients, 52 intra-lesional excisions with wide margins on 16
      patients, and 17 incomplete excisions on 3 patients. One patient, with intra
      pelvic lesions, died of a massive haemorrhage 3 days after surgery. Forty
      patients were followed from between 3 and 29 years. One, who had a multicentric
      EADT for 21 years, died from the disease. The significant factors concerning
      local recurrence after wide procedures were an unsatisfactory initial wide local
      excision, disease affecting 4 or more muscles and the invasive nature of the
      recurrences. We recommend wide local excision of these tumours in all anatomical
      areas that allow this procedure. When major nerves and vessels are involved, we
      recommend an intralesional excision with wide margins in order to preserve limb
      function. Radiation therapy should be confined to cases in which wide local
      procedures are not feasible. Overall, 37 of our patients (90%) were cured of the
      disease, 2 had their disease controlled, and 2 died.

PMID- 8567159
TI  - Fractures of the humerus in arm wrestling.
AB  - Two cases of spiral fracture of the humerus, which occurred during arm wrestling,
      are reported. The possible mechanism is discussed.

PMID- 8567160
TI  - The effect of low dose diclofenac sodium administered locally on heterotopic bone
      formation in rats.
AB  - The effect of a low dose of diclofenac sodium, administered locally, on
      heterotopic bone formation in rats was investigated. Heterotopic bone was induced
      by implantation of demineralised bone matrix into the gluteal muscles. Diclofenac
      was released continuously for 2 weeks from micro-osmotic pumps for each
      demineralised bone implant in the rats. Each had a control implant in the
      opposite gluteal muscle to which saline was released in the same way. The yield
      of new woven bone was determined after 4 weeks by measuring the ash-weights of
      the implants. Those of the diclofenac samples were significantly decreased
      compared to the controls. These results suggest that a low dose of diclofenac
      given locally decreases heterotopic bone formation in rats.

PMID- 8567161
TI  - Fine structure and distribution of lymphatics in the synovial membrane of monkey
      and human knee joints. A study using an enzyme-histochemical method.
AB  - The fine structure and distribution of lymphatics in the synovial membrane of
      monkey knee joints, and human knees with osteoarthritis and rheumatoid arthritis,
      were studied by light and electron microscopy using an enzyme-histochemical
      method. Whole mount preparations and tissue sections were doubly stained for 5'
      nucleotidase and alkaline phosphatase. The 5'-nucleotidase positive lymphatics
      could be distinguished from the alkaline phosphatase positive blood vessels. In
      monkey specimens the 5'-nucleotidase lymphatics were densely distributed in the
      medial and lateral parts of the suprapatellar pouch and infrapatellar fat pad, in
      both the superficial and deep of the sublining cell layers. Collecting lymphatics
      were well developed in the deep fibrous layer and in the merging epimysium. In
      the knees with both types of arthritis, the patterns of distribution were the
      same as in the monkey. No lymphatics were found in well developed villi in
      rheumatoid arthritis, but many blood vessels were present.

PMID- 8567162
TI  - Aneurysm of the superficial palmar arch. A case report.
AB  - We describe a case of compression of the median nerve by an aneurysm of the
      superficial palmar arterial arch which presented with symptoms of the carpal
      tunnel syndrome. The traumatic and occupational nature of true palmar aneurysms
      are discussed.

PMID- 8567163
TI  - Osteochondroma of the peroneal tubercle. A report of two cases.
AB  - We report two patients with pain on the lateral side of the ankle and foot which
      was due to stenosing tenosynovitis of the peroneal tendons caused by an
      osteochondroma of the peroneal tubercle. Surgical treatment produced a good
      result in both cases. The condition is uncommon, but should be borne in mind as a
      possible cause of pain in this region.

PMID- 8567164
TI  - Chemical synthesis of phosphopeptides using the arylthio group for protection of
      phosphate: application to identification of cdc2 kinase phosphorylation sites.
AB  - Synthesis of two O-phosphorylated dipeptides, N-Boc-O[S,S-bis(p
      methoxyphenyl)phosphorodithioyl] -serylproline and N-Boc-O-[S,S-bis(p
      methoxyphenyl) phosphorodithioyl]threonylproline, as new O-phosphorylated
      dipeptide building blocks for the synthesis of O-phosphorylated peptides, is
      described. Peptides containing phosphoserine or phosphothreonine were prepared by
      use of these building blocks in the Boc mode of liquid-phase peptide synthesis.
      Sites phosphorylated by cdc2 kinase were easily identified using these chemically
      synthesized phosphopeptides.

PMID- 8567165
TI  - The immunomodulatory diversity of the proteins of the transforming growth factor
      beta (TGF beta) family.
AB  - The examination of immunomodulatory properties of oligopeptides derived from two
      exposed loops (containing thymopentin-like and tuftsin-like sequences,
      respectively) of the proteins belonging to TGF beta family suggests that the
      particular species of the TGF beta family should differ distinctly in their
      influence on the immune response. According to our results obtained from three
      TGF beta species of mammals, TGF beta 2 should be a strong immunosuppressor,
      whereas for TGF beta 3 the immunostimulative potency is more probable. TGF beta 1
      species would possess both immunosuppressive and immunostimulative potency,
      residing in two different loops of the protein. The results obtained also suggest
      that chicken TGF beta 4 should be associated with immunostimulative effects and
      xenopus TGF beta 5 with immunosuppressive ones.

PMID- 8567166
TI  - Convergent solid-phase peptide synthesis. 12. Chromatographic techniques for the
      purification of protected peptide segments.
AB  - The purification of a range of protected peptide segments has been carried out
      using modified reversed-phase chromatographic techniques in which DMF was added
      to the water and acetonitrile mixtures used as eluents. The purity of the
      recovered peptides was excellent and recoveries were high in all cases, even for
      longer hydrophobic segments. In several cases purifications were carried out on
      the hundreds of milligrams scale. For protected peptide segments containing Met,
      protection as the sulfoxide avoids its unwanted alkylation and oxidation, and the
      increased overall polarity can be useful in the purification of protected
      peptides incorporating this residue.

PMID- 8567167
TI  - Solution and solid-state structure of the diketopiperazine of tyrosyl
      tetrahydroisoquinoline-3-carboxylic acid.
AB  - delta-Selective antagonism of [L-Tic2]-peptides, including the simple dipeptide
      Tyr-L-Tic-NH2, is linked to the Tyr-Tic-"recognition site". In order to gain
      further information on the conformational preferences of the Tyr-Tic-moiety we
      have undertaken a structural study of a cyclic analog, the diketopiperazine of
      Tyr-Tic. A conformational study of cyclo[-Tyr-Tic-], that is almost devoid of
      opioid activity, can also be useful to discriminate between the role of the two
      aromatic rings and of the basic nitrogen in determining antagonism. The structure
      of cyclo[-Tyr-Tic-] has been solved in a DMSO/water solution at 278 K by NMR
      spectroscopy and in the solid state by X-ray diffraction methods. The two
      informations are almost identical, with an arrangement of the aromatic rings
      rather different from that of the putative bioactive conformation of the parent
      linear dipeptide. This difference points to the importance of conformational
      effects and is in agreement with the hypothesis that the positive center may be
      not essential for antagonism.

PMID- 8567168
TI  - Effector-induced dissociation of glyceraldehyde-3-phosphate dehydrogenase
      discriminated by urea solvation.
AB  - The dissociation of glyceraldehyde-3-phosphate dehydrogenase (GAPD) from pig
      muscle in water solutions (0.1 M phosphate, pH 7) at increased urea
      concentrations was studied by means of frontal-gel chromatography, intrinsic
      (TRP) fluorescence, differential absorption spectroscopy and selective chemical
      modification at TRP0193. The results are in agreement with a consecutive two-step
      model of dissociation of the tetramer and the dimer (C*T = 0.42 M urea < C*D =
      1.39 M urea). The binding effector(s) destabilizes the oligomeric structures
      (delta GT changes from -1.00 to -0.54 kcal/mol; delta GD from -2.30 to -1.22
      kcal/mol). The introduction of the bulky Koshland-reagent group to TRP-193 at the
      subunit-subunit interface leads to a decrease of the stability with delta delta G
      approximate to 1 kcal/mol, owing to TRP-193...TYR-39...TYR-92 cluster
      destruction. By using lobster GAPD atomic coordinates (PDB file 1GPD) and pig
      muscle GAPD amino-acid sequence, a tentative molecular model was constructed and
      the subunit contacts in terms of the Lee-Richard static accessibilities were
      described. A detailed analysis of the dissociation as a transfer of the buried
      residues from the molecular interface to the urea solutions was performed.

PMID- 8567169
TI  - Synthesis of the basic-helix-loop-helix region of the immunoglobulin enhancer
      binding protein E47 and evaluation of its structural and DNA binding properties.
AB  - The basic-helix-loop-helix (bHLH) region of the immunoglobulin enhancer binding
      protein E47 (IEB E47) was prepared in high yield by a solid-phase peptide
      synthesis methodology. Size-exclusion chromatography, sedimentation equilibrium
      and cross-linking data showed that the synthetic bHLH protein, 1, was dimeric,
      and higher-order aggregates of trimer and tetramer were also observed. The
      circular dichroism spectrum of 1 showed a high helical content, which increased
      upon addition of DNA containing the kappa E2 sequence. Gel mobility shift
      experiments showed that protein 1 bound sequence specifically to the kappa E2
      sequence with a binding constant of 10(-10) M2, and had an affinity for other E
      box sequences as well. Comparisons between the co-crystal structure of IEB E47
      with DNA and structural studies in solution showed lower helical contents in
      solution as would have been predicted from the crystal structure.

PMID- 8567170
TI  - New cyclic bradykinin antagonists containing disulfide and lactam bridges at the
      N-terminal sequence.
AB  - Continuing our studies of the bioactive conformation of bradykinin (BK)
      antagonists, we synthesized a first series of analogues with side-chain
      cyclization in the N-terminal sequence. Through this conformational constraint it
      should be possible to gain insight into their three-dimensional structure. The
      cycles were proposed on the basis of existing ideas and hypotheses about the
      receptor bound conformation of BK and its antagonists. The reported peptides
      contain D-Phe at position 7 or D-Tic-Oic (D-Tetrahydroisoquinoline-3 -carboxyl
      octahydroindole-2-carboxylic acid) at positions 7 and 8, respectively, and a
      disulfide or lactam bridge between positions 0 and 6. Syntheses, including
      cyclization reactions, were carried out on PAM resin. The biological activity of
      the lead compound [DPhe7]-BK, the linear precursors and the cyclic peptides, as
      estimated on isolated rat uterus, guinea pig ileum and lung strips, are in the
      same range. The conformational properties of the new cyclic analogues were
      studied through energy minimization on a model compound. The results of the
      calculations support the existence of low-energy structures containing a beta
      turn. Therefore, such a turn in the N-terminal segment of the molecule can be
      proposed as an important structural feature of the bioactive conformation of BK
      antagonists.

PMID- 8567171
TI  - Structural and charge requirements for antimicrobial and hemolytic activity in
      the peptide PKLLETFLSKWIG, corresponding to the hydrophobic region of the
      antimicrobial protein bovine seminalplasmin.
AB  - Several analogs of the 13-residue antimicrobial and hemolytic peptide
      PKLLETFLSKWIG (SPF), which is the most hydrophobic region of the 47-residue
      antimicrobial protein seminalplasmin [Sitaram, N. & Nagaraj, R. (1990) J. Biol.
      Chem. 265, 10438-10442] have been synthesized. The antimicrobial and hemolytic
      properties of the peptides were investigated with a view to gain a insight into
      the structural and charge requirements for these activities of SPF. Peptides in
      which E was replaced by K exhibited considerably improved antimicrobial activity
      with no concomitant increase in hemolytic activity. A peptide in which the
      aromatic amino acids were replaced by leucine exhibited antimicrobial activity
      like those of the peptides which had aromatic amino acids. Interchange in the
      positions of E and K and total replacement of K by E resulted in complete loss of
      activity. The peptides having antimicrobial activity like those of the peptides
      which had aromatic amino acids. Interchange in the positions of E and K and total
      replacement of K by E resulted in complete loss activity. The peptides having
      antimicrobial activities showed appreciable helical content in a hydrophobic
      environment, whereas inactive peptides did not. Thus, by suitable 'engineering'
      the biological activity of a short 13-residue peptide can be altered by yield
      peptides specifically having only antimicrobial activity with increased potency.

PMID- 8567172
TI  - Synthesis of peptide amides using Fmoc-based solid-phase procedures on 4
      methylbenzhydrylamine resins.
AB  - A two-step low-high protocol for the efficient synthesis of peptide amides is
      described. The protocol exploits the efficiency of Reagent K for side-chain
      deprotection with the capability of the hard acid trifluoromethane-sulfonic acid
      (TFSMA) for cleavage of the peptide from the benzhydrylamine resin. This
      procedure has proven to be an effective method for the synthesis of peptide
      amides. The formation of alpha-aminosuccinimide (Asu) derivatives were observed
      with aspartyl-containing peptides as a minor side reaction product of this
      procedure, but this Asp-->Asu rearrangement could be successfully suppressed by
      employing low temperature conditions. The N- to O-acyl rearrangement of threonine
      and/or serine residues also only occurred to a minor extent under these synthetic
      conditions.

PMID- 8567173
TI  - Role of amino and carboxyl groups of cobrotoxin in the conformational stability
      and the interaction with acetylcholine receptor.
AB  - To study the functional involvements of the common interaction of the Leu-1 alpha
      amino group and Asp-58 in cobrotoxin, the lysine epsilon-amino groups of
      cobrotoxin were initially guanidinated with o-methylisourea. The alpha-amino
      group of Leu-1 was them modified with TNBS after the guanidination of cobrotoxin.
      Both modified derivatives displayed no significant changes in the secondary
      structure and antigenicity of cobrotoxin, whereas the binding affinity for
      nicotinic acetylcholine receptor (nAChR) was pronouncedly decreased when Leu-1
      was modified. Six out of seven free carboxyl groups and the remaining buried Glu
      21 carboxyl group of cobrotoxin were modified with glycine methyl ester in the
      absence and presence of guanidine HCl, respectively. Alternation in the beta
      sheet secondary structure of cobrotoxin was observed with the carboxyl-group
      modified derivatives, which caused a decrease in the binding activity of the
      toxin molecule to the antibody and nAChR. Moreover, modification of the Glu-21
      carboxyl group of cobrotoxin further reduced the nAChR binding activity, while
      the antigenicity remained unchange. Thus, our results conclude that the Glu-21
      residue and the common interaction of the terminal Leu-1 alpha-amino group and
      the Asp-58 carboxyl group are related to the nAChR-binding activity of
      cobrotoxin, and the free carboxyl groups in cobrotoxin are conformation
      essential.

PMID- 8567174
TI  - Determination of the ratios of the aromatic amino acid residues by first- or
      second-derivative UV spectrometry for a simple characterization of peptides.
AB  - A method for the simultaneous determination of the ratios of the three aromatic
      amino-acid residues in peptides was set up in acidic conditions. Binary and
      ternary mixtures of these amino acids were prepared, and first- and second
      derivative spectra then calculated from their 0.1 nm resolution spectra between
      240 and 320 nm. Certain spectral bands were chosen to differentiate tyrosine from
      tryptophan on the first-derivative spectra, and phenylalanine from tyrosine and
      tryptophan on the second-derivative spectra. Variation of the amplitude of the
      chosen bands was shown to be a linear function of the ratio of the aromatic amino
      acids in the mixture. This technique was validated with peptides whose sequence
      was known. The difference between theoretical and experimentally determined
      ratios was lower than 10%. Since the results are obtained as ratios, neither the
      concentration nor the nature of the peptide has to be known. The feasibility of
      application using a photodiode array detector with high resolution in reversed
      phase high-performance liquid chromatography is discussed.

PMID- 8567175
TI  - Drastic reduction in antimicrobial activity by replacement of Orn residues with
      Lys in cyclized amphiphilic beta-structural model peptides.
AB  - Recent investigation have indicated that cyclic dodeca- and tetradecapeptides,
      cyclo(-Leu-Orn-Leu-Orn-D-Phe-Pro)2 (Orn-DLL-12) and cyclo(-Leu-Orn-Leu-Orn-Leu-D
      Phe-Pro)2 (Orn-DLL-14), which are designed on the basis of a cyclic beta
      structural antibiotic, gramicidin S (GS), inhibit the growth of Gram-positive and
      -negative bacteria with high potency [Ando, S., Nishikawa, H., Takiguchi, H.,
      Lee, S. & Sugihara, G. (1993) Biochim. Biophys. Acta 1147, 42-49]. In this study
      we designed and synthesized two analogs, Lys-DLL-12 and Lys-DLL-14, in which four
      Orn residues in Orn-DLL-12 and Orn-DLL-14 were replaced by Lys residues,
      respectively, and investigated their interactions with model membranes in terms
      of CD and dye-leakage experiments, antimicrobial activity and lytic activity for
      human erythrocytes. Both peptides newly designed showed no antimicrobial activity
      and no lytic activity of erythrocytes. The present CD study showed that the
      presence of neutral liposomes and of acidic liposomes of natural or synthetic
      phospholipids results in no remarkable conformational difference between Orn-DLL
      12/-14. The leakage experiment showed a clear relation between the antimicrobial
      activity and the leakage ability in acidic synthetic phospholipid liposomes but
      no correlation in acidic natural ones. The difference in hydrophobic and
      hydrophilic balance between Orn-DLL-12/14 and Lys-DLL-12/14 (derived from the
      increasing hydrophobicity due to an increase of four methylene units by the
      substitution of Lys for Orn) may be one of the important factors in the drastic
      decrease in activity.

PMID- 8567176
TI  - Chemical and enzymatic treatment of endothelin.
AB  - Endothelin-1 (ET), the most potent vasoconstrictor yet discovered, is a peptide
      containing 21 amino acids with two intrachain disulfide bridges. With the aim of
      obtaining two-chain derivatives, Et was submitted to chemical and enzymatic
      treatments. Reaction of ET with CNBr in 70% HCOOH gave, in addition to the
      expected [Hse7 lactone]-7,8-seco-ET and unreacted material, a by-product whose
      molecular weight was 25 m.u. greater than that of ET. When the reaction mixture,
      after lyophilisation, was immediately quenched with NH3-saturated dry MeOH, two
      products could be recovered in a 5:1 ratio, both obtained by nucleophilic attack
      of the homoserine lactone: the expected [Hse7-NH2]-7,8-seco-ET and [Hse7]ET,
      resulting from competitive intramolecular reaction of the deprotonated alpha
      amino group of the Asp8 residue. The Lys9-Glu10 bond turned out to be very
      resistant to enzymatic attack both by Lys-C-endopeptidase and trypsin. The 9,10
      seco-ET derivative could be obtained by treatment with Lys-C-endopeptidase only
      by using a high enzyme/ET ratio and after a prolonged incubation time. Cleavage
      of the Lys9-Glu10 bond could not be achieved by treatment with trypsin, even with
      a high enzyme/substrate ratio. The main product was 13,14-seco-ET, deriving from
      the action of chymotripsin (present as an impurity in the trypsin preparation) on
      Tyr13. The structure of these peptides was confirmed by amino-acid sequence
      analysis and fast atom bombardment mass spectrometry (FAB-MS). Nicking of the ET
      structure at different positions had different impact on the biological
      properties of the resulting derivatives.

PMID- 8567177
TI  - In vitro association of the phosphatidylinositol 3-kinase regulatory subunit
      (p85) with the human insulin receptor.
AB  - The insulin receptor, as a consequence of ligand binding, undergoes
      autophosphorylation of critical tyrosyl residues within the cytoplasmic portion
      of its beta-subunit. The 85 kDa regulatory subunit of phosphatidylinositol (PI) 3
      kinase (p85), an SH2 domain protein, has been implicated as a regulatory molecule
      in the insulin signal transduction pathway. For the present study, glutathione S
      transferase (GST) fusion proteins of p85 SH2 domains were used to determine if
      such motifs associate directly with the autophosphorylated human insulin
      receptor. The p85 N + C (amino plus carboxyl) SH2 domains were demonstrated to
      associate with the autophosphorylated beta-subunit, while neither the GTPase
      activator protein (GAP) N SH2 domain nor the phospholipase C-gamma 1 (PLC gamma
      1) N + C SH2 domains exhibited measurable affinity for the activated receptor.
      The p85 N SH2 domain demonstrated weak association with the insulin receptor,
      while the p85 C SH2 domain alone formed no detectable complexes with the insulin
      receptor. The association of p85 N + C SH2 domains with the autophosphorylated
      receptor was competed efficiently by a 15-residue tyrosine-phosphorylated peptide
      corresponding to the carboxyl-terminal region of the insulin receptor, but not by
      phosphopeptides of similar length derived from the juxtamembrane or regulatory
      regions. The insulin receptor C domain phosphopeptide inhibited the p85 N + C SH2
      domain-insulin receptor complex with an IC0.5 of 2.3 +/- 0.35 microM, whereas a
      10-residue phosphopeptide derived from the insulin receptor substrate 1 (IRS-1)
      competed with an IC0.5 of 0.54 +/- 0.10 microM. These results demonstrate that,
      in vitro, there is an association between the p85 regulatory protein and the
      carboxyl-terminal region of the activated insulin receptor that requires the
      presence of both the N and C SH2 domains. Furthermore, formation of the
      p85/insulin receptor complex may lead to signaling pathways independent of IRS-1.

PMID- 8567178
TI  - Chemical synthesis and characterization of ShK toxin: a potent potassium channel
      inhibitor from a sea anemone.
AB  - ShK-toxin, a 35 residue peptide isolated from the sea anemone Stichodactyla
      helianthus, was synthesized using an Fmoc strategy and successfully folded to the
      biologically active form containing three intramolecular disulfide bonds. The
      ability of synthetic ShK toxin to inhibit specific [125I]-dendrotoxin I binding
      to rat brain membranes slightly exceeded (was more potent than) that of the
      natural ShK toxin sample, but was comparable with previously reported data for
      ShK toxin. The peptide toxin inhibited [125I]-charybdotoxin binding to Jurkat T
      lymphocytes with an IC50 value of 32 pM. In addition, Jurkat T lymphocytes Kv1.3
      potassium channels were inhibited with an IC50 value of 133 pM. Owing to their
      unique structure and high affinity for at least some potassium channels, ShK
      toxin and related sea anemone potassium channel toxins may become useful
      molecular probes for investigating potassium channels.

PMID- 8567179
TI  - Stereochemical analysis of the antigenic tip of the V3 loop peptide of HIV-1
      gp120.
AB  - A novel multiple turn conformation has been observed for a segment GPGRAFY in the
      crystal structure of a complex of HIV-1 gp120 V3 loop peptide with the Fab
      fragment of a neutralizing antibody [Ghiara et al. (1994) Science 264, 82-85]. A
      structural motif has been defined for the peptide segment, employing idealized
      backbone conformations characterized by ranges of virtual C alpha torsion angles
      and bond angles. A search of 122 high-resolution protein crystal structures has
      permitted identification of 24 examples of similar structural motifs. Two major
      conformational families have been identified, which differ primarily in the
      conformation at residue 3. The observed conformation at residue 3 in family 1 is
      left-handed helical (alpha L) and that in family 2 is right-handed helical (alpha
      R). Of the 10 examples in family 1, 9 examples have Gly residues at position 3.
      Of the 12 examples in family 2, 7 examples have Asn/Asp at position 3. Computer
      modeling of the V3 loop tip sequence using the two backbone conformational
      families as starting points leads to minimum-energy conformations in which
      antigenically important side-chains occupy similar spatial arrangements. This
      stereochemical analysis of the V3 loop tip sequence suggests a rational basis for
      the design of synthetic analog peptides for use as viral antagonists or synthetic
      antigens.

PMID- 8567180
TI  - Isolation and identification of C-terminal peptides of proteins.
AB  - A method for the isolation and identification of C-terminal peptides of proteins
      has been developed. The procedure entails the racemization of the C-terminal
      amino acid by reaction of the N-trifluoroacetylated protein with acetic anhydride
      and pyridine. After deprotection, the protein is fragmented to yield a mixture of
      peptides, which in turn are digested with carboxypeptidases. All peptides are
      hydrolyzed to L-amino acids except the C-terminal peptide with the terminal D
      amino-acid residue. It is resistant to the action of carboxypeptidases and is
      readily identified by peptide mapping.

PMID- 8567181
TI  - Simulations of conformers of tuftsin and a cyclic tuftsin analog.
AB  - The conformational properties of the configurational isomers of tuftsin, a linear
      tetrapeptide with the sequence Thr-Lys-Pro-Arg, were investigated with six 1 ns
      molecular dynamics simulations in explicit water and in a 1.0 m NaCl solution.
      The average conformation of the cis isomer is a type VI beta-turn. Our results
      indicate that water-peptide hydrogen bonding, in addition to intramolecular
      hydrogen bonds, stabilizes the cis conformer. The trans isomer is neither a beta-
      nor a gamma-turn. Results are compared with parallel studies on a cyclic analog
      of tuftsin, cyclo(Thr-Lys-Pro-Arg-Gly). The addition of salt does, not influence
      the backbone conformation of the peptide. Differences between the structures are
      confined to the side-chain orientations of the Lys and Arg residues.

PMID- 8567182
TI  - Conformation and activity of +H2-Pro-Leu-Gly-NH2 and its analogues modified at
      the leucyl residue.
AB  - In order to investigate the relation between the conformation and the ability to
      modulate dopamine receptors, conformational free-energy calculations using an
      empirical potential (ECEPP/3) and hydration shell model were carried out on the
      tripeptide +H2-Pro-Leu-Gly-NH2 (PLG) and its analogues in which the Leu residue
      is replaced with Phe, Ahx (L-2-aminohexanoic acid), Ile, Abu and Ala residues in
      the unhydrated and hydrated states. PLG and two tripeptides possessing Phe and
      Ahx residues show dopamine receptor modulating activity, while the other
      tripeptides do not. Irrespective of activities, PLG and its analogues are found
      to have the high probabilities to form beta-bends of types II and I in the
      unhydrated state. However, in the hydrated state, the beta-bend probabilities of
      the PLG analogues decrease significantly compared with those in the unhydrated
      state. These results indicate that the beta-bend structure is a necessary factor
      for the PLG analogues to be active, but not a sufficient factor, and that the
      interactions of water molecules with the backbone may force the tripeptides to be
      more distorted or extended. The size and the orientation of the hydrophobic
      moiety of the second residue seem to be of consequence in eliciting the activity
      of the tripeptides.

PMID- 8567183
TI  - Chemical synthesis and biological activities of the EGF-like domain of mouse
      schwannoma-derived growth factor (SDGF).
AB  - Schwannoma-derived growth factor (SDGF), an epidermal growth factor (EGF) family
      peptide recently discovered, has an EGF-like domain in the carboxyl terminal
      portion. In this study, we synthesized mSDGF(38-80) corresponding to the EGF-like
      domain of mouse SDGF by means of stepwise solid-phase method using Fmoc chemistry
      in order to evaluate the biological function of the EGF-like domain in SDGF. The
      linear peptide of mSDGF(38-80) was folded by direct oxidation with reduced and
      oxidized glutathione to form intramolecular disulfide bridges in synthetic
      peptide. On the biological activity, we examined mitogenic activity induced by
      mSDGF(38-80) in NIH/3T3 fibroblast cells and interaction with EGF receptor in
      A431 cells. In the results, mSDGF(38-80) was confirmed to form three disulfide
      linkages that were similar in pattern to EGF by amino acid and sequence analysis
      of fragments obtained after thermolytic digestion. However, mSDGF(38-80)
      possessed weak mitogenic activity in NIH/3T3 cells and weak binding affinity for
      the EGF receptor in A431 cells compared with those of human EGF. These results
      suggest that the EGF-like domain of SDGF may have little effect upon mitogenic
      activity and the EGF receptor binding of SDGF.

PMID- 8567184
TI  - The role of the C-terminus of the insulin B-chain in modulating structural and
      functional properties of the hormone.
AB  - Within the scope of structure-function studies on the proteohormone insulin, the
      role of the C-terminal segment B26-B30 for self-association and receptor
      interaction was analyzed. Insulin derivatives with modifications in the region
      B26-B30 were synthesized by trypsin-catalyzed coupling reactions of des-(B23-B30)
      insulin with synthetic peptides. The peptides were obtained by Fmoc solid-phase
      peptide synthesis. Insulins with multiple amino acid-->glycine substitutions were
      examined to distinguish between the influence of the side chains and the
      influence of the main chain in positions B27-B30 on the self-association of the
      hormone. The analogues [GlyB27,B28,B29,B30]insulin and [GlyB27,B28,B30]insulin
      exhibit relative receptor affinities of 80% and self-associate. The successive
      extension of [AlaB26]des-(B27-B30)-insulin-B26-amide (relative receptor binding
      273%) with amino acids corresponding to the native sequence B27-B30 showed the
      influence of the length of the B-chain on receptor affinity: the extension by B27
      threonine amide reduces receptor binding to 71%, all further prolongations have
      only small effects on the binding. The effect of the B28-side chain on main-chain
      conformation, self-association and receptor binding was examined with [XB28]des
      (B29-B30)-insulin-B28-amides (X = Phe, Gly, D-Pro). While the glycine and D
      proline analogues (relative binding 104 and 143%, respectively) retain the self
      association properties typical of insulin, [PheB28]des-(B29-B30)-insulin-B28
      amide (relative binding 50%) shows diminished self-association. The backbone
      modified insulin derivative [SarB26]des-(B27-B30)-insulin-B26-amide (sarcosine =
      N-methylglycine) exhibits an unexpectedly high receptor affinity of 1100% which
      demonstrates that the B26-amide hydrogen of the native hormone is not important
      for receptor binding.

PMID- 8567185
TI  - Effect of the environment and role of the pi-pi stacking interactions in the
      stabilization of the 3(10)-helix conformation in dehydroalanine oligopeptides.
AB  - A quantum-mechanical study of the chain-length dependent stability of the
      extended, 2(7)-ribbon and 3(10)-helix conformations in dehydroalanine (delta Ala)
      oligopeptides has been performed. To address the study, the oligopeptides delta
      Ala(n), where n varies from 1 to 6, were computed by using the semiempirical AMI
      methodology. Cooperative free-energy effects permit one to predict the
      stabilization of the 3(10)-helix with respect to the extended and 2(7)-ribbon
      conformations when the number of residues in the polypeptide chain increases. The
      interactions associated with the pi-electron density of the side chains can
      easily explain this finding. The effects of the solvent and the crystalline
      packing on the different conformations were modeled using a self-consistent
      reaction field (SCRF) method and a molecular mechanics approach to the packing,
      respectively. Both the aqueous and crystal environments seem to be a key factor
      in the stabilization of the helical conformation. Finally, the variations of
      electrostatic parameters such as atomic point charges and dipole moments in delta
      Ala-containing peptides with internal (conformation) and external (solvent)
      effects are discussed.

PMID- 8567186
TI  - Amino-acid sequence of bone Gla protein from the African clawed toad Xenopus
      laevis and the fish Sparus aurata.
AB  - As an initial step in the analysis of bone Gla protein (BGP; osteocalcin)
      function in lower vertebrates, we have developed a simple and rapid method for
      the isolation of BGP from bone and have applied this to the isolation of BGP from
      the African clawed toad Xenopus laevis and the fish Sparus aurata. We have also
      determined the complete amino-acid sequence of Sparus and Xenopus BGP, including
      the identification of the sites of y-carboxylation. Since the addition of Xenopus
      and Sparus BGP sequences significantly extends the range of species whose BGP
      structures are known, we have compared the 18 presently known BGP sequences.
      Twelve amino acids are invariant in these 18 BGP sequences and are therefore
      presumably critical to BGP conformation or function. Eight of these 12 invariant
      amino acids are also invariant in all presently known matrix Gla protein
      sequences (shark, mouse, rat, cow, human), an observation which strongly supports
      the evolutionary relationship between these two vitamin K-dependent bone proteins
      and suggests that the proteins may adapt similar tertiary structures.

PMID- 8567187
TI  - Solution structure of the B-chain of insulin as determined by 1H NMR
      spectroscopy. Comparison with the crystal structure of the insulin hexamer and
      with the solution structure of the insulin monomer.
AB  - The solution structure of the isolated B-chain of bovine insulin has been
      determined by 1H NMR spectroscopy combined with simulated annealing calculations.
      Complete sequence-specific assignments for the proton resonances are reported
      together with a set of 309 NOEs used in the structure calculations. Chemical
      shift variations from random coil values provide support for the existence of
      helical regions in the polypeptide chain, as do a characteristic series of d
      alpha beta(i, i + 3) NOEs from residues B8 to B17. While there is some evidence
      for a limited degree of conformational averaging over the helical region, in
      general the helix is relatively well defined and corresponds closely to the
      helical region seen in the X-ray crystal structure of the insulin hexamer. Other
      similarities with the crystal structure include turn-like conformations at the
      carboxy terminal end of the helix and extended strands at both the amino and
      carboxy termini of the peptide. These similarities between the crystal structure
      and the isolated B-chain suggest that this peptide has intrinsic folding
      properties, which allow it to adopt its characteristic structure in intact
      insulin without the need for extensive cooperative interactions with the A-chain.
      Despite these general similarities, an important difference between the isolated
      B-chain and the intact protein occurs in the carboxy terminal region. This region
      appears significantly more mobile in the isolated B-chain. As a conformational
      change involving the carboxy terminus has been implicated in receptor binding,
      the current study of the isolated B-chain provides valuable information on the
      extent of this region's intrinsic mobility.

PMID- 8567188
TI  - Synthesis and activity of the glutathione analogue gamma-(L-gamma-azaglutamyl)-L
      cysteinyl-glycine.
AB  - The backbone-modified glutathione analogue gamma-(L-gamma-azaglutamyl)-L
      cysteinyl-glycine 7, characterized by the presence of a NHCONH urea linkage
      deriving from the replacement of the native Glu gamma-CH2 with the aza (NH)
      group, was synthesized and fully characterized by FAB-MS, 1H- and 13C-NMR.
      Potential of 7 and its oxidized form 6 as gamma-glutamyltransferase inhibitors
      was investigated. Both compounds 7 and 6 were found to be competitive inhibitors
      of hog kidney gamma-glutamyltransferase (EC 2.3.2.2.) by binding at the donor
      site: the reduced analogue is a more efficient inhibitor than glutathione of the
      gamma-glutamyl transfer reaction. Inhibition at the acceptor site, which is also
      present, appears to be more complex. In particular, un-competitive inhibition is
      observed for compound 7. The results indicate that gamma-azapeptides of type 7
      may represent interesting targets in the search for stable inhibitors of gamma
      glutamyltransferases.

PMID- 8567189
TI  - A new clustering system for protein sequences and its application to constraints
      discovery in protein evolution.
AB  - A conceptual clustering system, CLUSMOL/S, has been developed to classify protein
      sequences from a user-defined point of view. Given a grouping of amino acids as a
      viewpoint, the system constructs taxonomic trees of sequences based on minimum
      information criterion. Every tree node expresses itself as a generic consensus
      sequence that consists of specific consensus amino acids insertion/deletion
      points, and generic amino acids with a specified character. The resulting tree
      and generic sequences show the similarity-based relationships among sequences and
      their characteristics. Application to vertebrate cytochromes c yields an
      acceptable cladrogram only when amino acids are grouped by volume and length of
      sidechains. The result indicates that the steric factor is the most important
      constraint in the process of protein evolution.

PMID- 8567190
TI  - Anxiety in medically ill older patients: a review and update.
AB  - OBJECTIVE: The authors review the evaluation and treatment of anxiety symptoms in
      elderly patients, with particular emphasis on elderly patients with chronic
      medical illness. METHODS: A computer search for articles addressing anxiety
      symptoms in patients sixty-five and older was supplemented by the authors'
      clinical experience and knowledge of other literature and textbooks relevant to
      the topic. RESULTS: Ten to 20 percent of older patients experience clinically
      significant symptoms of anxiety. Anxiety complaints may represent the
      physiological consequence of treatable medical illness, the result of psychiatric
      illness, or an exaggerated or normal response to life events. Both
      psychopharmacologic and nonpharmacologic treatments can be effective in relieving
      symptoms. CONCLUSIONS: Careful differential diagnosis is an essential preliminary
      step to successful treatment. Non-pharmacologic interventions (behavioral
      treatments, in particular) may be effective for many patients. Consideration of
      both the benefits and the risks of medication management is recommended, as
      elderly patients are especially vulnerable to side effects.

PMID- 8567191
TI  - Female sexual side effects associated with selective serotonin reuptake
      inhibitors: a descriptive clinical study of 33 patients.
AB  - OBJECTIVE: After the advent of selective serotonin reuptake inhibitors on the
      U.S. market in 1988, American psychiatrists have been faced with more choices of
      antidepressants for the treatment of depression. The prescribing of SSRIs has
      been increasing in popularity because they are easily titrated by the physicians
      and tolerated by patients. However, the SSRI use is frequently associated with
      female sexual dysfunction. The aim of this study was to describe these SSRI
      associated female sexual side effects. METHODS: In a retrospective series, clinic
      records of 110 female SSRI-treated outpatients were reviewed for loss of or
      decreased libido, orgasmic disturbances (anorgasmia or delayed orgasm), as well
      as clinical management patterns to alleviate sexual side effects. RESULTS: Twenty
      one fluoxetine-, nine paroxetine-, and five sertraline-treated cases with female
      sexual inhibition were identified. The fates of SSRI-associated sexual adverse
      effects and clinical managements of restoring these side effects were described.
      CONCLUSIONS: With some limitations in interpreting the data, the findings of this
      study suggest that SSRI-associated female sexual dysfunction occurs at a higher
      rate than we previously thought, equal potentials in implicating female sexual
      side effects among three SSRIs, and the absence or the low incidence of female
      sexual adverse effects from bupropion, and that these side effects can be managed
      by waiting for a spontaneous remission, dosage reduction of SSRIs, substitution
      with bupropion and other antidepressants, or the use of an antidote.

PMID- 8567192
TI  - The neuropsychiatric aspects of boxing.
AB  - OBJECTIVE: To review the neuropsychiatry of boxing. METHOD: This update considers
      the clinical, neuropsychological, diagnostic, neurobiological, and management
      aspects of boxing-related brain injury. RESULTS: Professional boxers with
      multiple bouts and repeated head blows are prone to chronic traumatic
      encephalopathy (CTE). Repeated head blows produce rotational acceleration of the
      brain, diffuse axonal injury, and other neuropathological features. CTE includes
      motor changes such as tremor, dysarthria, and parkinsonism; cognitive changes
      such as mental slowing and memory deficits; and psychiatric changes such as
      explosive behavior, morbid jealousy, pathological intoxication, and paranoia.
      Screening with neuropsychological tests and neuroimaging may help predict those
      boxers at risk for CTE. CONCLUSIONS: Boxing results in a spectrum of CTE ranging
      from mild, nonprogressive motor changes to dementia pugilistica. Recent emphasis
      on safety in the ring, rehabilitation techniques, and other interventions do not
      eliminate the risk for CTE. For this reason, there is an active movement to ban
      boxing.

PMID- 8567193
TI  - The Mini Mental State Exam as a predictor of neuropsychological functioning after
      cardiac surgery.
AB  - OBJECTIVE: The present longitudinal study was designed to: 1) determine the
      ability of the Mini Mental State Exam (MMSE) to predict neuropsychologic
      impairment based on neuropsychologic testing five to seven days and six weeks
      after cardiac surgery; and 2) to determine whether the traditional or the
      education-related MMSE norms are more appropriate to use for this purpose.
      METHOD: The day before surgery (T1), before hospital discharge (T2), and six
      weeks after surgery (T3), 247 subjects completed a battery of five
      neuropsychologic tests. Subjects also completed the Center for Epidemiological
      Studies Depression Scale and the Speilberger State-Trait Anxiety Inventory.
      Subjects completed the MMSE two to three days after surgery. RESULTS: Stepwise
      regression analyses revealed that the MMSE significantly predicted only a small
      portion of the variance in neuropsychologic test performance at T2, and to an
      even lesser extent at T3, over and above the demographic variables. In assessing
      the association between an impairment score (derived from the neuropsychologic
      test battery) and the MMSE, we found that the traditional MMSE cut-off score
      maximized specificity (number of true negatives) while the education-adjusted
      MMSE cut-off scores maximized sensitivity (number of true positives).
      CONCLUSIONS: These results suggest that although the MMSE is widely used to
      assess cognitive mental status, it may have limited value in identifying patients
      with cognitive impairment post-cardiac surgery, and special attention must be
      paid to the cut-off scores used in interpreting the MMSE.

PMID- 8567194
TI  - Cytochrome P450 monooxygenases and interactions of psychotropic drugs: a five
      year update.
AB  - OBJECTIVE: This article is a five-year update on a previous review article
      (International Journal of Psychiatry in Medicine, 21:47-56, 1991) on cytochrome
      P450 monooxygenases and interactions of psychotropic drugs. METHOD: In the
      literature review, the recent committee work on nomenclature of the P450
      superfamily are highlighted. Then, the author reviewed gene clusters of three
      human cytochrome P450s--CYP1A2, CYP2D6, and CYP3A4 with the focus on the changes
      of serum levels of the coadministered psychotropic drugs in the context of
      enzymatic induction and inhibition of these three hepatic enzymes. RESULTS: As
      indicated in one table, the author stratified probes, inducers, inhibitors,
      chemical reactions, and substrates under these three gene clusters. As shown in
      another simple table, the author compared the hepatic enzymatic inhibitions of
      four selective serotonin reuptake inhibitors and pointed out the inhibition
      potentials of fluvoxamine at CYP1A2, fluoxetine and paroxetine at CYP2D6, and
      fluoxetine and fluvoxamine at CYP3A4 if these two SSRIs have higher serum
      concentrations. CONCLUSION: The author suggests that with these systematic
      approaches, this rapidly adding knowledge can help psychiatrists better
      understand psychotropic drug interactions and maximize the benefits of patients'
      psychopharmacotherapy.

PMID- 8567195
TI  - Effects of postpartum psychiatric illnesses on family planning.
AB  - OBJECTIVE: We investigated the relationship between postpartum psychiatric
      episodes and subsequent family planning. Our hypothesis was that women who had a
      postpartum illness would plan to have fewer children. METHOD: We conducted a mail
      survey of members of the self-help group Depression After Delivery (DAD). The
      membership was asked about changes in family planning after a postpartum illness.
      Two groups were defined: women who took action to prevent further pregnancies
      after the illness (CHANGE) and women who did not take action to prevent future
      pregnancies (NO CHANGE). RESULTS: Among respondents 32 percent changed their
      family plans after suffering a postpartum illness. Fear of recurrence, effects on
      the family, treatment costs and severity of the episode manifested by suicide or
      infanticide attempt, hospitalization, and prescribed medication were reasons
      given for altering plans. CONCLUSIONS: The postpartum illness dramatically
      changed some women's reproductive plans. Prevention strategies for these
      illnesses need to be addressed when women are making decisions about having other
      children.

PMID- 8567196
TI  - Introduction: needs-based technology assessment. Who can afford not to use it?

PMID- 8567197
TI  - Technology assessment. Old, new, and needs-based.
AB  - Recent health reports, including the 1993 World Development Report, have
      emphasized the importance of integrating the needs of the population into
      technology assessment. This paper reviews previous approaches to technology
      assessment and identifies the missing link between technology and its impact on
      the physical, emotional, and social needs of the community, namely needs-based
      technology assessment. It stresses the key role played by issues of equity and
      community values in making technology decisions. A number of models for needs
      based technology assessment are described.

PMID- 8567198
TI  - Health transition and needs-based technology planning and implementation.
AB  - Investment in health can offer additional benefits to development independent of
      economic improvement. Many technologies have been useful in improving the health
      of the people in the past. However, rapid and often unpredictable change has
      contributed to the inequity, inefficiency, and rising cost of health care. This
      paper outlines why a needs-based approach to assessing any new technology in the
      health sector is essential. To respond to changing needs, capacities within the
      health care system, several of which are described here, must be strengthened.
      Needs-based technology planning and implementation is affordable and feasible and
      is crucial in order that both health as a basic human right and good health at
      low cost can be attained.

PMID- 8567199
TI  - Investing in health wisely. The role of needs-based technology assessment.
AB  - Countries worldwide spend huge sums on health--about $1,700 billion a year, or
      roughly 8% of global income. But the World Development Report 1993: Investing in
      Health shows that these monies could be spent much more wisely, in the process
      doing a great deal to help the world's 1 billion poor. Essential national public
      health and clinical packages are proposed based on assessment of the burden of
      disease (measured in disability adjusted life years) and the cost-effectiveness
      of interventions. Governments can play a central role in improving the health of
      their citizens: they can foster an environment that enables households to improve
      health and they can also improve their own spending on health, targeting it to
      support universal access to essential national public health and clinical
      packages based on the above methods. This is a good example of the concept of
      needs-based technology assessment, combining the disciplines of epidemiology,
      economics, and policy formulation. When applied, it should lead to improved
      effectiveness, efficiency, and equity.

PMID- 8567200
TI  - Case study: assessing laparoscopic cholecystectomy. The GVHS experience.
AB  - This article describes the experience at the Greater Victoria Hospital Society of
      assessing the appropriateness of introducing laparoscopic cholecystectomy (lap
      chole) within the framework of an established technology assessment process. Lap
      chole promised to deliver cost savings; however, these could only be realized by
      capitalizing on the reduced length of stay by removing the surgical beds from
      service. A cautionary note is raised as to whether the increased use of lap chole
      in the population is appropriate.

PMID- 8567201
TI  - Case study: needs-based technology assessment and essential national health
      research. Experience in the Philippines.
AB  - Essential national health research (ENHR) ensures that health research will be
      undertaken in priority areas defined by the people and will be used in decision
      making. Needs-based technology assessment (NBTA) is anchored on the ENHR
      philosophy. Two case studies are presented, one illustrating a successful
      application of NBTA and the other a failed approach. Reasons for the difference
      in success are examined.

PMID- 8567202
TI  - Case study: World Health Organization-International League of Associations for
      Rheumatology Community-Oriented Programme for the Control of Rheumatic Diseases
      (WHO-ILAR COPCORD) in Indonesia and Brazil.
AB  - The three-stage World Health Organization-International League of Associations
      for Rheumatology Community Oriented Programme for Control of Rheumatic Disease
      (WHO-ILAR COPCORD) is described. Stage I results from Indonesia and Brazil are
      presented. This is a needs-based approach that offers efficiency in large-scale
      survey research that aims to estimate the prevalence of rheumatic diseases. It
      saves human resources, time, and cost in the collection of epidemiologic data.
      Awaited with interest are the results of the next two stages of COPCORD, which
      involve the development of educational programs on rheumatic disease and the
      evaluation of their impact on the burden of illness.

PMID- 8567203
TI  - Case study: practical tools for improving needs-based health management and
      technology assessment. The PHC MAP series.
AB  - This paper outlines the need for and development of a practical set of tools to
      improve needs-based health management and technology assessment. International
      reports have documented the lack of adequate information for the managerial
      process in primary health care. The components of the Primary Health Care
      Management Advancement Program (PHC MAP) Series, designed for both manual and
      computer applications, are described. The series has been widely pretested and is
      currently being implemented by many government health services and
      nongovernmental organizations worldwide. Information is included indicating how
      the PHC MAP materials may be obtained.

PMID- 8567204
TI  - International variation in intervention rates. What are the implications for
      patient selection?
AB  - While international variations in intervention rates are well recognized, little
      is known about their implications for patient selection. This paper describes an
      exploratory study in which the probability of undergoing an elective intervention
      (surgery for benign prostatic hyperplasia) in an area in the United Kingdom was
      compared with an area in the United States. It found that the area with high
      intervention rates was associated with higher levels of surgery in men with low
      levels of need who are unlikely to gain much benefit.

PMID- 8567205
TI  - Variation in use of breast-conserving surgery in Lombardia, Italy.
AB  - The extent of variation in the use of breast-conserving surgery was analyzed
      using the 1990 and 1991 hospital discharge data of Lombardia, Italy. The
      proportion of patients undergoing breast-conserving surgery for unilateral breast
      cancer was estimated for each of the 10 geographic areas (9 provinces plus
      metropolitan Milano) in which the region is divided. Overall, the rate of use was
      41% of 3,225 patients in 1990, and 45% of 3,736 patients in 1991. In both study
      years, patient age was strongly correlated with the likelihood of undergoing
      conservative surgery, with younger women more frequently treated with this
      approach. In each province, patients treated at centers located in the main city
      had a greater probability (OR, 1.54; 95% CI, 1.37-1.69) of having conservative
      surgery. This procedure was also more often used in private hospitals (OR, 1.59;
      95% CI, 1.20-2.08) where care is paid at the point of consumption by patients,
      directly or through their private insurance. The observed variation in the use of
      the conservative procedure across the 10 regional areas was greater than that
      expected by chance alone (p < .0001), with rates ranging from 29% to 60%. This
      pattern persisted even after adjusting for the relevant patient and hospital
      characteristics. Despite the relatively large body of scientific evidence, it
      appears that the surgical management of breast cancer is more dependent on
      physicians' attitudes in each geographic area than on individual patients'
      characteristics.

PMID- 8567206
TI  - Perioperative use of total parenteral nutrition. Variations in guidelines and
      practice in three Norwegian hospitals.
AB  - In a cross-sectional, retrospective study of 604 cases, variations among three
      Norwegian hospitals in use of perioperative parenteral nutrition (TPN) after
      gastrointestinal surgery was determined. Postoperative TPN rates were 25%, 34% (p
      = .05) and 56% (p < .0001), respectively. However, a substantial part of the
      variation was explained by differences in patient characteristics.

PMID- 8567207
TI  - Why is the pharmaceutical industry investing increasing amounts in health
      economic evaluations?
AB  - Over the last few years, the pharmaceutical industry has financed an increasing
      number of health economic evaluations. The purpose of this article is to describe
      how and why the pharmaceutical industry is applying health economic evaluations.
      Seven different fields of application are identified, and the varying reasons for
      use are discussed.

PMID- 8567208
TI  - Is there a relationship between the volume of work carried out in intensive care
      and its outcome?
AB  - This paper reports the results of a study of the association between volume of
      activity and patient outcome in 26 intensive care units in the United Kingdom.
      Hospital fatality rates showed a statistically significant (p = .016) negative
      association with volume. However, mean APACHE II scores, as a measure of the
      severity of case mix, were also negatively associated with volume (p = .021).
      Thus, one explanation of the lower death rates at higher volumes is that larger
      units admit less severely ill patients. For patients admitted immediately after
      surgery, the correlation between severity standardized mortality ratios and
      volume (while not significant, p < .1) suggests there may be a volume-output
      effect unexplained by severity.

PMID- 8567209
TI  - Prostheses for primary total hip replacement. A critical appraisal of the
      literature.
AB  - Eighty-one published papers on the performance of prostheses in total hip
      replacement were appraised. Sound methodology was demonstrated in 1 of 8
      randomized controlled trials and 4 of 17 nonrandomized comparative studies. Of 56
      case series without controls, 32 met the appraisal criteria, but these are
      intrinsically less useful. The published literature does not provide solid
      evidence for the superiority of cement-free or hybrid prostheses over modern
      cemented types.

PMID- 8567210
TI  - The evolution of laparoscopic surgery in routine health care.
AB  - While laparoscopic cholecystectomy is now widely used, diffusion of other
      laparoscopic surgical methods has been more modest. Uptake of most laparoscopic
      methods has been influenced by considerations of effectiveness compared with open
      surgery, competing minimally invasive therapies, and the inconvenience and cost
      of technical change.

PMID- 8567211
TI  - Assisted conception techniques. On what basis do health technologies become
      routinely available when they have been assessed as effective?
AB  - The possibility of restoring fertility among some infertile couples through
      assisted reproductive technology has led to questions about the terms under which
      such treatments should be made available. Although there is now evidence on their
      effectiveness, there is considerable variation in the availability of these
      treatments under the U.K. National Health Service.

PMID- 8567212
TI  - Report from the Agencia D'avaluacio de Tecnologia Medica (CAHTA).

PMID- 8567213
TI  - Report from the Canadian Coordinating Office for Health Technology Assessment
      (CCOHTA). Guidelines for economic evaluation of pharmaceuticals: Canada.

PMID- 8567214
TI  - Report from the EUR-ASSESS Project.

PMID- 8567215
TI  - Technology alert from the University Hospital Consortium (UHC). Drug Monographs.

PMID- 8567216
TI  - [Therapy of heart failure. Digitalis, diuretic plus ACE inhibitor or more?].

PMID- 8567217
TI  - [Treatment and recurrence prevention ulcerative colitis].

PMID- 8567218
TI  - [Interferon-alpha in therapy of malignant hemoblastoses].

PMID- 8567219
TI  - [New supportive therapy measures in acute lung failure].

PMID- 8567220
TI  - [Therapy and prevention of pneumocystis carinii pneumonia].

PMID- 8567221
TI  - [Differential therapy of chronic fatigue syndrome].

PMID- 8567222
TI  - [Renaissance of tuberculosis?].

PMID- 8567223
TI  - [Secondary prevention of coronary heart disease with lipid lowering drugs.
      Evaluating outcome eliminates the controversy].

PMID- 8567224
TI  - [Backache, claudicatio venosa and chronic diarrhea].

PMID- 8567225
TI  - [78-year-old patient with chronic epigastric pain].

PMID- 8567226
TI  - [Acarbose in therapy of diabetes].

PMID- 8567227
TI  - [New strategies in the treatment of chronic viral hepatitis].

PMID- 8567228
TI  - [May (must?) in a for recurrent thrombophlebitis [with normal AT III/ protein
      C+S] fully "marcumarized" patient (with [otherwise?] negative contraindications)
      with acute posterior wall infarct (15 min "old") a brief lysis therapy be
      instituted?].

PMID- 8567229
TI  - [To what extent can prostaglandin synthesis inhibitors of the non-steroidal
      antirheumatic (NSAR) type modify the effect of ACE inhibitors?].

PMID- 8567230
TI  - [What is the incidence of synchronous second cancers of the large intestine and
      of metachronous second cancers of the large intestine?].

PMID- 8567231
TI  - [Comments on the contribution by P. Stiefelhagen. Possibilities and limits of
      modern intensive medicine].

PMID- 8567232
TI  - [Hyperuricemia].

PMID- 8567233
TI  - Diagnostic pitfalls of fine needle aspiration cytology for breast disease.
AB  - We analysed 1500 consecutive fine needle aspiration cytology (FNAC) specimens to
      ascertain the reasons for diagnostic failure. Of 221 tumours proven malignant
      following open biopsy, 184 (83%) were correctly diagnosed on FNAC. Of 1082
      aspirates classified 'benign', 787 (73%) underwent open biopsy and of these 33
      (4%) were diagnosed malignant. All three cases of ductal carcinoma in-situ (DCIS)
      and eight of 16 lobular carcinomas in this study were missed using FNAC alone.
      Twelve of the 22 patients with invasive carcinoma not diagnosed on cytology had
      tumours measuring less than 1 cm diameter. Six of 1500 FNAC reports (0.4%) gave
      false positive diagnoses, five were classified as 'suspicious of malignancy; and
      one as 'frankly malignant'. The overall sensitivity was 84%, specificity 99% and
      positive predictive value 97%. Though these results confirm the value of FNAC as
      a rapid means of diagnosing most breast cancers, it it unreliable in patients
      with invasive carcinomas less than 1 cm in diameter and for the detection of
      lobular and in-situ carcinoma.

PMID- 8567234
TI  - Intra-coronary stents--extending the role of angioplasty in angina--initial
      experience.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) is a widely successful
      revascularisation procedure. The restenosis rate has not significantly improved,
      despite the addition of many therapeutic agents. We describe the role of intra
      coronary stents in the management of recurrent occlusion, restenosis and
      intracoronary dissection. We describe and discuss the problems associated with
      placement of the stent. The intracoronary stent has a successful adjuvant role to
      play with angioplasty in reducing both the elective and emergency requirements
      for coronary artery bypass grafting.

PMID- 8567235
TI  - Treatment of endobronchial haemangiomas with Nd:YAG laser.

PMID- 8567236
TI  - Laparoscopic closure of acutely perforated duodenal ulcer--an early experience.
AB  - Laparoscopic closure of an acutely perforated duodenal ulcer is an alternative
      procedure to open surgery. With proper training and experience this procedure
      might overtake laparotomy and simple closure thereby reducing the post operative
      morbidity in terms of reduced wound pain, short hospital stay, likely reduced
      wound sepsis and hernia occurrence and post operative chest complications. This
      article describes four patients with acute perforation of duodenal ulcer who were
      submitted to an emergency laparoscopic repair.

PMID- 8567237
TI  - Night sedation in pregnancy--inappropriate prescribing.

PMID- 8567240
TI  - Patient education and childhood asthma--fashion or progress?

PMID- 8567239
TI  - Nutrition in the elderly.

PMID- 8567238
TI  - Prevention of adhesion formation.

PMID- 8567241
TI  - The management of skin disorders in the elderly.

PMID- 8567242
TI  - Declining sperm counts and increasing incidence of testicular cancer and other
      gonadal disorders: is there a connection?

PMID- 8567243
TI  - Sister Mary Joseph's nodule.

PMID- 8567244
TI  - Epidemiology of tumours of the central nervous system in Ireland.
AB  - The incidence of cancer of the central nervous system (CNS) was established for
      the counties of Cork and Kerry using the Southern Tumour Registry data base. A
      total of 191 newly-diagnosed patients were identified over the five year period
      1984-1988. This represents a crude annual incidence rate of 7.3 per 100,000 for
      males and 6.8 for females. When the incidence rates were adjusted using the
      accepted theoretical World Population, the annual rates were 6.7 and 6.4 for
      males and females respectively. These levels are higher than those reported for
      England and Wales (5.2 for males and 3.6 for females) and Scotland (5.9 for males
      and 4.2 for females). However the Irish rates are much lower than the most recent
      published statistics for Denmark which report rates of 12.9 for males and 11.8
      for females. The risk of being affected by a CNS tumour increases substantially
      from 50 years onwards for a male and from 40 years on for females. The risk is
      seen to diminish for those aged 80 years or more. The most common locations of
      CNS tumours were the frontal, parietal and temporal lobes. Gliomas were by far
      the most common type of tumour.

PMID- 8567245
TI  - School nutrition survey.
AB  - Food we eat has an important influence on health and well-being. Many eating
      habits are established in childhood. 456 children aged eight to 12 years
      participated in this survey of food eaten at school. Of all the food items eaten
      as a snack, 48.6% were categorised as junk. 75.8% of the sandwiches brought to
      school for lunch were made with white bread. Of the remaining food items brought
      for lunch 63.5% were of the junk variety. Compared with those who brought a snack
      or lunch from home, those given money to buy their own were more likely to eat
      junk (p < 0.01). Food eaten at school reflects approximately one third of a
      child's daily food intake but health food practises for even a third of food
      intake may be of a value for health and long term eating habits. Nutritional
      education with the reinforcement of high nutritional standards in schools could
      improve the situation.

PMID- 8567246
TI  - Fragile X syndrome--a review.
AB  - Since the discovery of the Fragile X syndrome some 20 years ago, there have been
      numerous articles concerning clinical features, cognitive profile and
      transmission. It is a syndrome of importance to all those working in the mental
      health field and those involved in community health, such as General
      Practitioners, since it is second only to Down syndrome as a genetic cause of
      mental handicap.

PMID- 8567247
TI  - A geographical distribution of mortality and deprivation.
AB  - Because of the paucity of data on the geographical distribution of mortality and
      deprivation in the Republic of Ireland, we calculated SMRs for each county for
      the years 1982-6. Two measures of mortality were used, all cause and avoidable
      mortality. Two indexes of deprivation were also calculated for each county,
      Townsend's and a new Irish index. Significant differences in mortality exist
      between counties. Counties that had SMRs significantly below the national
      standard of 100 were Meath, Donegal and Galway. Counties with significantly high
      SMRs were Louth, Limerick and Westmeath. County SMRs were correlated with both
      deprivation indexes and no significant correlation was found to explain the
      apparent differences in mortality.

PMID- 8567248
TI  - The role of overlength of the leg in aseptic loosening after total hip
      arthroplasty.
AB  - A study was done on the role of postoperative leg length inequality (LLI) in
      aseptic loosening after total hip arthroplasty (THA). Data on 405 McKee-Farrar
      hip replacements performed at the Invalid Foundation, Helsinki, Finland were
      available for the study. The mean lengthening of the operated leg was 0.8 cm
      after an average follow-up of 7.7 years. Of these hips, 63 (15.6%) subsequently
      underwent revision due to aseptic loosening of the prosthesis. Several risk
      factors were analysed using multivariate stepwise regression analysis to find
      factors which predispose patients to loosening: overlength of the operated limb
      proved to be the most important. Our conclusion is that overlengthening should be
      avoided by careful preoperative and intraoperative length measurements and proper
      selection of prostheses. If there is marked overlengthening of the replaced hip
      postoperatively, it should be corrected.

PMID- 8567249
TI  - Dynamic varus heel cup: a new orthosis for treating pes planovalgus.
AB  - Pes planovalgus is an extremely common deformity and still not completely
      understood. Its pathogenesis and the possibilities for treating it with shoe
      inserts are still under debate. While the controversy between abstentionists and
      interventionists remains a fact, since a certain number of flat feet persist into
      adult age and cause disability, a new type of orthosis is proposed. This has been
      tested on children affected with grade III pes planovalgus and with all the worst
      clinical, objective and prognostic parameters. The study was carried out with a
      control group using traditional Lelievre insoles. The results were extremely good
      and correction was achieved in a significantly higher number of patients than in
      the control group.

PMID- 8567250
TI  - Preliminary study of a new fixation device for intertrochanteric femoral
      fractures.
AB  - The authors present a preliminary study on the treatment of intertrochanteric
      fractures with a reinforced 95 degrees blade-plate, devised and used at the II
      Orthopedic Dept. of the University of Milan, in cooperation with the Milan
      Polytechnic. They discuss the indications and clinical-radiographic findings of
      the first 14 cases operated on, with a mean follow up of two years.

PMID- 8567251
TI  - Screw sockets: survivorship analysis after eight years.
AB  - A comparative analysis of the radiographic results of 111 screw sockets (65
      tapered and 46 hemispherical cup sectors) was made to evaluate both their
      behaviour over a period of time and the validity of their use today. The follow
      up was performed on average 42 months after the implant. Overall survivorship
      shows a high risk of failure during the fourth year and a greatly increased rate
      of failure after the sixth year. Comparison of the survival curves of the two
      types of acetabular component revealed no significant differences. The two types
      considered were, however, of different sizes: the implanted taper sockets were on
      average 6.6 mm larger than the comparable hemispherical cup sector acetabular
      components, thus involving a greater loss of acetabular bone.

PMID- 8567252
TI  - Spinal fusion induced by porous hydroxyapatite blocks (HA). Experimental
      comparative study with HA, demineralized bone matrix and autogenous bone marrow.
AB  - Numerous materials have been studied and recently used in clinical practice as
      synthetic bone biosubstitutes to integrate or even replace autogenous bone
      grafts. This study consisted of an experimental vertebral fusion model in rabbits
      using porous hydroxyapatite (HA), both alone and in various combinations with
      demineralized bone matrix (DBM), as a vehicle for the osteoinductive agent (Bone
      Morphogenetic Protein-BMP), and with autogenous bone marrow (BM), which supplies
      BMP-sensitive reticular cells. The animals were divided into two main groups on
      the basis of the physical form of the biomaterial implanted: HA blocks and HA
      granules, which in turn included several subgroups based on the composition of
      the implants (HA, HA+DBM, HA+BM, HA+DBM+BM). There were also control groups with
      no implant or with bone autografts (ACB). Two months after the operation,
      analysis of the results (radiograph, fusion stability test on dynamic
      radiographs, histological evaluation) demonstrated the following: clinical and
      radiographical results of the group implanted with HA blocks were superimposable
      on those with autogenous bone grafts, especially in the subgroup treated with DBM
      and BM, while in the group implanted with granules the results were poor, thus
      indicating the fundamental influence of the physical state of the biomaterial on
      bone ingrowth. This was then further confirmed by the histological study in the
      HA block group, whereas the HA granule group showed a certain fibrous reaction
      around the granules with poor porous bone ingrowth.

PMID- 8567253
TI  - Partial cervicosternotomy: a useful anterior surgical approach to the
      cervicothoracic junction.
AB  - Access to the cervicothoracic junction, whether by lower anterior cervical or
      transthoracic approach, is particularly difficult. The authors propose partial
      cervicosternotomy which allows the T3-T4 disk to be reached satisfactorily in 50%
      of cases and in the remaining 50% allows direct anterior control of the upper two
      thirds of T3. The advantage of this approach is that it provides direct access to
      the cervicothoracic junction without leading at the same time to the
      reconstruction problems caused by the uni- or bilateral sternoclaviculotomies
      proposed until now. A detailed anatomical study of the arrangement of the
      intercostal vessels shows that this strictly median approach presents no risk to
      the medullary vessels thanks to the abundant anastomoses in this region. However,
      the use of this method may be limited if the aortic vessels have an anomalous
      origin. Pre-operative angiography is therefore necessary each time T3 must be
      reached. This approach has already been successfully used in tumor surgery for
      excision and reconstruction of lesions involving the cervicothoracic region.

PMID- 8567254
TI  - Critical analysis of intramedullary nailing by the Ender method in the treatment
      of intertrochanteric fractures.
AB  - A retrospective study was carried out to evaluate the results of intramedullary
      fixation by Ender nailing in the treatment of intertrochanteric fractures. During
      the period 1980-1989, 85 patients were treated with this method at the Orthopedic
      Department of the Universita Cattolica in Rome. Evaluation of the cases took into
      account the patient's characteristics (age, sex, weight, height, obesity,
      previous or concomitant illness, level of autonomy, mental condition, type of
      fracture, time elapsed before operation and laboratory tests), details of the
      operation (length, accuracy of reduction and mechanical fixation stability, post
      operative hospitalization period and general and local complications) and follow
      up evaluation (X-ray examination, functional examination and evaluation of the
      results). Analysis of the observations showed that, although it induced less
      surgical trauma, internal fixation by the Ender method did not ensure a stable
      reduction, particularly with highly comminuted and basicervical fractures. As a
      result, the elective indication for this method should be restricted to stable
      intertrochanteric fractures, particularly in patients with a generally poor
      condition.

PMID- 8567255
TI  - Surgical treatment of arthritic valgus knee: femoral supracondylar osteotomy or
      knee replacement?
AB  - Twenty-two of the 24 patients operated on with femoral supracondylar osteotomy
      for arthritic valgus knee between 1978 and 1987 were evaluated, comparing the
      results with those obtained in a similar group of 10 patients with the same
      disorder treated with knee replacement during the same period. From a functional
      viewpoint and according to the Hospital for Special Surgery rating scale, the
      results of the osteotomy were not significantly different from the extremely
      positive outcome of the knee replacement. However, as far as pain is concerned,
      only 50% of the osteotomy patients were completely asymptomatic after the
      operation. In the 50% of the osteotomy patients with post-operative under or over
      correction of the mechanical axis of the knee, the results were unsatisfactory.
      Finally, there was only one case of delayed union. In the light of these results,
      in contrast to what has been said by other authors, femoral osteotomy may be
      considered a valid alternative to knee replacement in the treatment of arthritic
      valgus knee in active subjects, less than 65 years old, with a valgus angulation
      of no more than 15 degrees and Ahlback stage 2 beta arthritis of the lateral
      compartment. It is, however, a technique which requires extreme precision both in
      planning and performing the operation.

PMID- 8567256
TI  - Surgical treatment of pubic pain refractory to conservative treatment.
AB  - After some considerations on the biomechanical nature of pubic pain, the authors
      present a series of 17 leading athletes (14 professional football players, 1
      marathon runner, 1 weight-lifter and 1 French boxer), complaining of this
      disorder for at least one year and refractory to conservative treatment,
      surgically treated with the Nesovic technique and evaluated after an average
      follow-up period of two years (18-30 months).

PMID- 8567257
TI  - Femoral neck preservation in total hip replacement.
AB  - Preservation of the femoral neck in hip arthroplasty creates a particular
      biomechanical situation which is clearly different from what is found even after
      partial neck removal. The femoral neck consists in fact of a "cylinder of
      cortical bone" that can be used as the "base" for anchoring the stem to the
      femur, in contrast to the press-fit procedure or other solutions. The mechanical
      and biological advantages are as follows: 1) Primary triplanar stem stability, in
      particular rotational stability. Rotational movements of the stem are blocked by
      the tough lateral cortical cylinder of the neck. Resistance to varus-valgus
      stress and collapse is also increased vertically and frontally. 2) Proximal
      cortical fixation. Primary fixation of the stem is provided by the neck cortex,
      whereas its mid-distal part is merely held by the metaphyseal cancellous bone and
      the tip is undersized with respect to the medullary canal. 3) Stress loads
      distributed along physiological lines of stress. Retention of the neck permits
      preservation of the trabecular systems, along which the stress is distributed
      towards the diaphysis and the greater trochanter. 4) Elasticity of the bone
      prosthesis system. Most of the stem is contained within the metaphyseal
      cancellous bone that lies between the prosthesis and the cortical bone, creating
      a bone-prosthesis module with variable and integrated elasticity. 5) Preservation
      of the bone-stock. The amount of residual bone following implant of the
      prosthesis increases, not only because of the presence of the femoral neck, but
      also as a result of the preservation of most of the metaphyseal cancellous bone.
      There is therefore greater bone-ingrowth, which is also favoured by the fewer
      changes in the endosteal blood supply. 6) Prosthesis revision is simpler, since
      the stem can easily be removed and a second neck resection performed. Our
      clinical and experimental studies, together with those of Freeman et al., confirm
      that the femoral neck is present for a long time after implant. Finally, we
      report a study of 200 prostheses with a follow-up of 1 to 6 years, demonstrating
      neck reabsorption in only 1% of the cases.

PMID- 8567258
TI  - Chiari osteotomy in association with intertrochanteric osteotomy in adults.
AB  - The authors report the results obtained in 34 adult patients suffering from early
      degenerative arthritis of the hip following mixed dysplasia in which the
      reduction in the central-edge angle and the increase in the acetabular index is
      associated with modification of the neck-shaft angle and/or femoral anteversion.
      These patients underwent a combined Chiari iliac osteotomy (C.I.O.) and
      intertrochanteric osteotomy (In.O.). The results indicate that, when the
      indications and technique are respected, C.I.O. associated with In.O. is a
      reliable surgical method.

PMID- 8567259
TI  - Post-operative intervertebral discitis. Evaluation of 12 cases and study of ESR
      in the normal postoperative period.
AB  - Twelve cases of intervertebral discitis following lumbar discectomy were
      evaluated and ESR was assessed in 70 patients operated on and without evidence of
      postoperative infection. Six of the intervertebral discitis patients were studied
      retrospectively and 6 prospectively. In the retrospective group, patients
      reported that symptoms appeared on average 15 days after the operation.
      Antibiotic treatment generally began 31 days after the operation and lasted 62
      days; symptoms regressed after 3.9 months. All patients showed long-term
      radiographic vertebral changes and osteolysis in the cases treated later. In the
      prospective group, the first symptoms appeared on average 5 days after the
      operation, treatment started after 8 days and lasted 41 days. Symptoms regressed
      after 1.8 months. There were only 3 cases of vertebral radiographic changes. In
      both groups, ESR was always more than 70. The most useful diagnostic imaging
      tests were conventional tomography and MRI. Needle biopsy had no effect on the
      length of treatment. In 14% of patients without infective complications, ESR
      increased noticeably a week after the operation but, in contrast to the
      intervertebral discitis patients, it did not then continue to increase. Close
      post-operative observation permitted early detection of intervertebral discitis.
      Early and high-dose antibiotic treatment, even if unspecific, can resolve this
      infection in a few weeks.

PMID- 8567260
TI  - Long-term results of cemented and screwed acetabular components.
AB  - The authors report their experience in the use of various types of acetabular
      components (cemented and screwed) in 253 hip prostheses with "Biodirect" femoral
      component and ceramic femoral head. A long-term follow-up of 148 hip prostheses
      (58.5% of the total) was carried out, 36 Muller type polyethylene and 61 Biolox
      ceramic acetabular components, and 51 screwed sockets of various models were
      used. From a clinical and radiographical standpoint, the ceramic acetabular
      component proved the most valid in the short and medium term, confirming the
      favourable biomechanical conditions which derive from ceramic/ceramic coupling.

PMID- 8567261
TI  - Remarks on the complications following ACL reconstruction using synthetic
      ligaments.
AB  - The authors analyse the method used between 1983 and 1990 in 161 patients with
      chronic anterior laxity of the knee treated by 162 ligament reconstructions
      utilizing synthetic ligament prostheses. Tearing of the prosthetic ligament is
      the most feared and frequent complication. This may be due to technical error,
      wear of the material or, to a lesser extent, new trauma. With a follow-up of up
      to 80 months, the number of tears seems excessively high. This means that
      artificial ligaments cannot today be considered a satisfactory surgical
      technique. The considerable technical improvements in autologous reconstructive
      surgery make the biological approach preferable even today.

PMID- 8567262
TI  - Scanning electron microscopy study of articular cartilage in the evolution of hip
      arthritis.
AB  - The authors report the results of scanning electron microscopy examination of
      samples of articular surface taken from 15 arthritic femoral heads removed during
      hip replacement. The specimens were collected from areas of the femoral head
      where different degrees of degenerative changes were identified, and processed
      with the normal techniques for scanning electron microscopy. A definition was
      made of the mechanisms leading to articular cartilage wear, the most obvious sign
      of cartilage degeneration. The earlier stages were characterized by the
      appearance of clefts in the surface layer, which merged and formed scales that
      flaked off, giving rise to superficial abrasions. The evolution of the
      degenerative process led to a deepening of the clefts, reaching the intermediate
      and deep layers and creating further scales of cartilage tissue, oblique or
      perpendicular to the surface. The elimination of these formations causes more or
      less marked wear that can extend down to the subchondral bone (ulcers and ground
      surfaces). As well as information on the condition of the articular surfaces,
      scanning electron microscopy may also provide details on the morphology and
      structure of the chondrocytes and the fibrillar network in the sagittal sections,
      showing the regressive phenomena associated with arthritis.

PMID- 8567263
TI  - Ulna non-union leading to Monteggia fracture deformity. Two cases of slowly
      developing radial head luxation.
AB  - The author presents two cases in which pseudoarthrosis of the ulnar diaphysis
      resulted in dislocation of the head of the radius. The pathogenesis of this
      secondary dislocation is discussed. The cause of anterior Monteggia fractures is
      not yet clear. Various explanations have been put forward: direct action of a
      force (Speed and Boyd, 1940), forced pronation (Evans, 1949) and hyperextension
      with strong contraction of the biceps (Wright, 1963). This work presents two
      cases of Monteggia fracture characterized by a "slow" fracture mechanism. The
      biomechanical aspects are discussed.

PMID- 8567264
TI  - Early diagnosis of congenital dysplasia of the infant hip by means of ultrasound
      screening.
AB  - The authors present a study carried out in 1990 analyzing the results of
      ultrasound screening of the infant hip in order to evaluate possible dysplasia.
      They stress the already unquestionable role of ultrasound screening as a valid,
      sensitive and useful device in the diagnosis of congenital dysplasia of the hip
      and emphasize that the earlier the examination is carried out, the easier it is
      to begin suitable treatment rapidly and with positive results. They recommend
      that ultrasound screening should be carried out by an orthopaedist in order to
      further shorten diagnosis and treatment times.

PMID- 8567265
TI  - [[Human parvovirus B19 and its clinical significance].
AB  - Human parvovirus B19 causes erythema infectiosum (fifth disease) and aplastic
      crisis. In pregnancy, B19 may be transmitted on to the fetus resulting in hydrops
      fetalis. B19 is sometimes associated with thrombocytopenia and vasculitis. In
      immunocompromised patients, B19 may persist causing chronic infection. Several
      methods for detecting B19 virus or specific antibodies are now available. B19
      infection does not usually require therapy. Efficacy of immunoglobulins in
      chronic B19 infection has been demonstrated.

PMID- 8567266
TI  - [Acquired ichthyosis-like skin disease. A challenge for diagnostic evaluation].
AB  - We report on four patients with acquired ichthyosis-like skin lesions seen in our
      out-patients' clinic in the last 6 years. Emphasis is placed on the case of a 25
      year-old patient who suffered from mycosis fungoides with the clinical features
      of an acquired ichthyosis-like condition. Three further observations illustrate
      the broad clinical spectrum of acquired ichthyosis-like dermatoses. In these
      patients renal insufficiency, HIV infection or an extreme diet were the cause of
      the skin lesions. Our observations emphasise that an acquired ichthyosis-like
      condition should be regarded as a challenge to make a definite diagnosis.
      Guidelines for a step-by-step diagnostic procedure are proposed.

PMID- 8567267
TI  - [Hair-like hyperkeratoses in patients with kidney transplants. A new cyclosporin
      side-effect].
AB  - We report a 31-year-old renal transplant patient treated with cyclosporin A who
      developed an unusual sebaceous gland hyperplasia accompanied by a disseminated
      follicular spiny hyperkeratosis. Those alterations were most evident on his face
      and limbs. In some locations hairy hyperkeratosis with authentic hair neogenesis
      was found. The histology of these alterations showed a marked hyperkeratosis of
      the hair follicles with formation of hair-like spikes either alone or in
      connection with hairs. The presence of true hairs distinguishes our case from the
      morphologically similar disseminated spiked hyperkeratosis and other spiny
      keratinization disorders. Scanning electron microscopy helped to demonstrate the
      hair-like structure of these keratoses. Some of the sebaceous glands showed
      cystic widening of their lumina, which were filled with abundant amorphous
      eosinophilic material, a finding similar to earlier observations. Our case
      demonstrates that these skin alterations should be classified as side effects of
      cyclosporin A and that they are apparently dose-dependent.

PMID- 8567268
TI  - [Angioma serpiginosum, a skin change along Blaschko lines?].
AB  - We present a 34-year-old woman with angioma serpiginosum on the medial aspect of
      the left thigh, extending to the groin and the lower abdomen, and on the volar
      aspect of the left forearm. In addition to the late onset, the distribution along
      the lines of Blaschko was a remarkable feature of this case. We therefore
      reexamined our recent cases of angioma serpiginosum. In 6 of 7 cases, the
      distribution indeed corresponded to the lines of Blaschko. Thus, we suggest
      adding angioma serpiginosum to the list of skin lesions that may follow the lines
      of Blaschko.

PMID- 8567269
TI  - [Amelanotic nodular malignant melanoma of the vulva. Case report and review of
      the literature].
AB  - We describe a 55-year-old woman with an amelanotic nodular malignant melanoma of
      the vulva. The tumour had developed within 3 months. Physical examination showed
      a solid, erythematous, centrally depressed nodular tumour with a waxy appearance.
      It was 1.3 cm across and located on the right labium majus. The surface was
      eroded and showed teleangiectasias. Histopathological examination revealed a
      nodular malignant melanoma with predominantly spindle-shaped tumour cells, stage
      IV-V, and 7.2 mm thick. The primary tumour was excised but the patient died of
      generalized metastases 19 months later. There are very few reports on melanoma of
      the vulva in the dermatological literature. In addition to this case report we
      review the literature and discuss the clinical picture, histopathology and
      prognosis of this melanoma.

PMID- 8567270
TI  - [Trichophyton soudanense as the pathogen of tinea corporis et capitis].
AB  - Tinea capitis and corporis caused by Trichophyton soudanense were identified in a
      6-year-old coloured boy who was born in Zaire and had been living for 3 years in
      Germany. This dermatophyte is very rarely seen outside the region in Africa where
      it is endemic. The disease is frequently overlooked at diagnosis because of the
      pathogen's capacity for causing chronic and oligosymptomatic infections. In our
      case the tinea did not a become apparent until the patient had been in Germany
      for 3 years. No-one else in his family had any comparable scalp or skin lesions.
      Consistent therapy with itraconazole (Sempera) dosed at 3 mg/kg body weight per
      day over a period of 4 weeks led to a permanent cure.

PMID- 8567271
TI  - [Pruritus of the artificial vagina of a transsexual patient caused by gonococcal
      infection].
AB  - Report on a 31-year-old male-to-female transsexual prostitute with a 3-week
      history of worsening pruritus and dysaesthesia in her neovagina, which had been
      constructed by means of penile skin invagination. The microbial diagnostic tests
      for sexually transmitted diseases (STD) showed gonococcal infection in the high
      vagina, while none was found in the urethra. Other STD and allergic contact
      sensitization were excluded. Despite the regularly stratified epithelium of the
      neovagina, which is physiologically resistant to gonococcal infection, this
      possibility must be considered in transsexual prostitutes.

PMID- 8567272
TI  - [Malignant infiltrating blue nevus of the plaque type. Case report and literature
      review].
AB  - We present, to the best of our knowledge, the first case of a malignant, primary
      plaque-type blue naevus in a 61-year-old male. Two biopsy specimens had been
      examined within 13 years, and revealed a common and cellular blue variant as a
      precursor. Locally invasive growth and regional lymph node swelling were present,
      but these alone could not confirm malignancy before evaluation of all clinical
      and histopathological features, as they are known to occur with benign cellular
      blue naevi. The recent literature and our case indicate that there is a malignant
      potential in every histological and clinical variant of blue naevus.

PMID- 8567273
TI  - [Multiple clear cell acanthomas].
AB  - Clear cell acanthoma is a rare, slow-growing benign epidermal tumour of
      adulthood. The prediction site of this usually solitary lesion is the distal part
      of the leg. Multiple clear cell acanthomas are very rare and are also found in
      other locations besides the typical site of predilection. In this paper we report
      on a 52-year-old man who--over a period of more than 20 years--had developed more
      than 100 of these tumours in all parts of his body. Although the histological
      diagnosis is easy, clinical recognition often proves difficult, especially in
      cases of multiple lesions. Different kinds of therapy for solitary and multiple
      lesions are discussed.

PMID- 8567274
TI  - [Porokeratosis plantaris, palmaris et disseminataa with multiple filiform
      hyperkeratoses and nail dystrophy].
AB  - We report on a family with porokeratosis plantaris, palmaris et disseminata with
      a very unusual clinical manifestation. The father showed an association of
      multiple filiform hyperkeratosis on the trunk with sparing of the palms and
      soles. In addition, this patient featured secondary nail dystrophy owing to
      porokeratosis. The daughter had an unusual course: the disease started on the
      trunk and did not spread to the palms and soles until later. In general the
      reverse is true.

PMID- 8567275
TI  - [Prescription formulations with clioquinol].

PMID- 8567276
TI  - [Chronic urticaria and hepatitis A].

PMID- 8567277
TI  - [Therapy of psoriasis with fumaderm preparation].

PMID- 8567278
TI  - [A gauze mouse for therapy].

PMID- 8567279
TI  - [Dermatologic pain therapy. Selected clinical aspects].

PMID- 8567280
TI  - What is a "radiation experiment"?

PMID- 8567281
TI  - Changes in soft tissue concentrations of plutonium and americium with time after
      human occupational exposure.
AB  - Concentrations of 239 + 240Pu and 241Am in human soft tissues (testes, thyroid
      gland, kidneys, spleen, heart, skeletal muscle, brain, and pancreas) were
      compared to those in livers of the same subjects. The subjects were volunteer
      donors with occupational exposures to plutonium and americium autopsied as part
      of the United States Transuranium and Uranium Registries program. The temporal
      distributions of tissue-to-liver ratios were compared to liver uptake fractions
      assumed on the basis of current models to estimate the initial uptake fractions
      for each tissue studied. Regressions of the ratios were used to compare tissue
      retention half-times to those of the liver. Effective half-times for plutonium
      and americium in the tissues studied were similar to those for the liver with
      three exceptions: (1) the clearance half-time for plutonium in kidneys is shorter
      than that of liver; (2) the retention half-time for plutonium in testes is longer
      than that of liver; and (3) the retention half-time for americium in skeletal
      muscle was longer than in the liver. Next to liver, the greatest initial uptake
      of systemic actinides was in skeletal muscle and the greatest initial
      concentrations were in the spleen. The uptake fraction of plutonium in the testes
      proposed by the ICRP was verified.

PMID- 8567282
TI  - Uncertainty of historical measurements of 131I in Hanford-area vegetation.
AB  - The Hanford Environmental Dose Reconstruction (HEDR) Project was conducted to
      estimate the radiation dose that individuals could have received as a result of
      emissions to the air and water from Hanford Site operations since 1944. The
      largest doses were to the human thyroid gland from 131I released into the
      atmosphere from Hanford facilities in the 1945-1947 time period. In support of
      the dose reconstruction effort, a database of historical environmental
      radioactivity measurements was constructed. This database includes measurements
      of total radioactivity for vegetation samples collected from 1945-1948 and
      counted using a Geiger-Mueller (GM) detector system. Because the factors used at
      that time to convert the GM counts to 131I activity did not take all parameters
      into account, and because some parameter values were inaccurate, more accurate
      conversion factors were developed as part of the HEDR Project. These factors can
      be used to estimate the actual historical activity levels. This paper summarizes
      the Monte Carlo uncertainty and sensitivity analysis methods used to assess the
      uncertainty of the newly reconstructed historical vegetation 131I activities and
      to identify the parameters that contributed the most uncertainty to these
      reconstructed activities. Based on the study of two vegetation (sagebrush)
      samples collected in the mid-1940's, it appears that the true 131I activity of
      the historical vegetation samples should be within a factor of three of the
      reconstructed activity. Also, the uncertainty in the parameter Icf (the fraction
      of the background-corrected GM measurement of a vegetation sample that resulted
      from 131I) was found to contribute the most uncertainty to the reconstructed 131I
      activities when the uncertainty in Icf was large.

PMID- 8567283
TI  - A numerical model for the analysis and evaluation of global 137Cs fallout.
AB  - Fallout 137Cs from atmospheric nuclear detonation tests has been monitored
      worldwide since the late 1950's. The deviation and the correlation among these
      monitoring data were analyzed, and their surface deposition characteristics were
      estimated by the compartment model developed in this research. In the analysis,
      the scale of space (i.e., size of each compartment) and the degree of detail
      (i.e., number of compartments) were statistically determined using the global
      distribution data of 137Cs. The mathematical model was evaluated by comparing the
      numerically stimulated results with the fallout monitoring data including the
      137Cs concentration in sea water. The major findings obtained in this research
      include that the deposition pattern of 137Cs is dependent on the latitude zone
      but not on the longitude, the mathematical model is promising for evaluating the
      dynamic performance of 137Cs in global atmospheric environment and its surface
      deposition, 137Cs is accumulated more in both the surface and deep ocean water of
      the North Pacific Ocean and the North Atlantic Ocean than that of other oceans,
      the 137Cs inventory is decreasing after the peak time in 1965, and the 137Cs
      inventory in the deep ocean water is decreasing more slowly than that in the
      surface ocean water.

PMID- 8567284
TI  - A genetic algorithm approach to optimization for the radiological worker
      allocation problem.
AB  - This paper describes a new approach to the radiological worker allocation problem
      using a multiple objective genetic algorithm. The worker allocation problem in
      radiological facilities involves various types of constraints and even mutually
      conflicting ones, such as individual dose limits, working time limits, etc. A
      major difficulty of this highly working time limits, etc. A major difficulty of
      this highly constrained problem is the way of finding an optimal solution in the
      huge search space where a large proportion of solutions are not feasible because
      some of the constraints cannot be satisfied. The paper proposes a model of
      evolution to establish an optimal assignment efficiently, based on the biological
      insights into the evolutionary process and heuristic ideas. The experimental
      results show a very rapid evolution to produce feasible solutions, and the
      application of multiple evaluation functions converges the feasible solutions to
      good ones. The genetic algorithm approach was found to be superior to the goal
      programming and simplex methods.

PMID- 8567285
TI  - Radiation impact from lignite burning due to 226Ra in Greek coal-fired power
      plants.
AB  - Lignite contains naturally occurring radionuclides arising from the uranium and
      thorium series as well as from 40K. Lignite burning is, therefore, one of the
      sources of technologically enhanced exposure to humans from natural
      radionuclides. Emissions from thermal power stations in gaseous and particulate
      form contain radioisotopes, such as 226Ra, that are discharged into the
      environment causing radiation exposures to the population. About 11,672 MBq y-1
      of 226Ra are discharged into the environment from four coal-fired power plants
      totalling 3.62 GW electrical energy in the Ptolemais Valley, Northern Greece, in
      which the combustion of 1.1 x 10(10) kg of lignite is required to produce an
      electrical energy of 1 GW y. The collective committed equivalent dose to lung
      tissue per unit power generated resulting from atmospheric releases of 226Ra was
      estimated to be 1.1 x 10(-2) person Sv (GW y)-1; i.e. more than 15 times higher
      than the average value for a modern type coal-fired power plant according to the
      UNSCEAR 1988 data.

PMID- 8567286
TI  - Radon measurements in underground dwellings from two prefectures in China.
AB  - Radon, an established lung carcinogen, remains the single most important
      environmental radiation exposure. Yet, an excess of lung cancer from breathing
      radon in homes has not been consistently demonstrated in studies conducted to
      date. To address several major problems that have hindered previous studies of
      lung cancer and radon in homes, we have embarked upon a lung cancer case-control
      study in Gansu Province, China, where a substantial proportion of the population
      live in underground dwellings. In this paper, we report on results of a pilot
      study in which radon measurements were made for 3 days in the summer in 40 homes
      under normal occupancy conditions using short-term E-PERM detectors and for 6
      months from February through August in 49 homes using long-term alpha-track
      detectors. Useable E-PERM data were obtained from 38 homes and useable alpha
      track data from 47 homes. For both types of detectors, measurements were
      approximately log-normally distributed. Arithmetic and geometric means were 233
      and 185 Bq m-3 (range 74-1,590 Bq m-3) for E-PERM measurements and 165 and 158 Bq
      m-3 (range 74-592 Bq m-3) for alpha-track measurements, respectively; 68% of E
      PERM measured homes and 55% of alpha-track measured homes exceeded 148 Bq m-3.
      Alpha-track measurements made at the entry, middle, and rear areas of the
      underground dwellings did not differ significantly (arithmetic means of 168, 162,
      and 165 Bq m-3 with standard deviations 63, 73, and 48, respectively), which
      suggests that air circulation may be minimal. The underground dwellings measured
      in the pilot study had high radon levels and the underground dwellers may provide
      an excellent population for studying indoor radon and risk of lung cancer.

PMID- 8567287
TI  - Statistical analysis of real-time, environmental radon monitoring results at the
      Fernald Environmental Management Project.
AB  - A comprehensive real-time, environmental radon monitoring program is being
      conducted at the Fernald Environmental Management Project, where a large quantity
      of radium-bearing residues have been stored in two covered earth-bermed silos.
      Statistical analyses of radon measurement results were conducted to determine
      what impact, if any, radon emitted by the radium bearing materials contained in
      the silos has on the ambient radon concentration at the Fernald Environmental
      Management Project site. The distribution that best describes the outdoor radon
      monitoring data was determined before statistical analyses were conducted. Random
      effects associated with the selection of radon monitoring locations were
      accommodated by using nested and nested factorial classification models. The
      Fernald Environmental Management Project site was divided into four general areas
      according to their characteristics and functions: 1) the silo area, where the
      radium-bearing waste is stored; 2) the production/administration area; 3) the
      perimeter area, or fence-line, of the Fernald Environmental Management Project
      site; and 4) a background area, located approximately 13 km from the Fernald
      Environmental Management Project site, representing the naturally-occurring radon
      concentration. A total of 15 continuous, hourly readout radon monitors were
      installed in these 4 areas to measure the outdoor radon concentration.
      Measurement results from each individual monitor were found to be log-normally
      distributed. A series of contrast tests, which take random effects into account,
      were performed to compare the radon concentration between different areas of the
      site. These comparisons demonstrate that the radon concentrations in the
      production/administration area and the perimeter area are statistically equal to
      the natural background, whereas the silo area is significantly higher than
      background. The study also showed that the radon concentration in the silo area
      was significantly reduced after a sealant barrier was applied to the contents of
      the silos.

PMID- 8567288
TI  - Giant dipole resonance neutron yields produced by electrons as a function of
      target material and thickness.
AB  - This paper characterizes the functional dependence of the giant dipole resonance
      neutron yield produced by electrons in terms of the atomic number (Z) and
      thickness (T) of the target. The yields were calculated by integrating, over the
      photon energy, the product of the differential photon track length and published
      photoneutron cross sections. The EGS4 Monte Carlo code and analytical formulas
      were used to calculate the differential photon track length. In thick targets,
      the Giant Dipole Resonance neutron yield approaches a saturation value as target
      thickness T increases to 10 radiation lengths. A formula, 8 x 10(-6) x (Z1/2 +
      0.12 Z3/2 - 0.001 Z5/2) n electron-1 MeV-1, developed from EGS4 calculations,
      estimates thick-target neutron yields for incident electron energies Eo above 50
      MeV. Giant dipole resonance neutron yields, calculated by several analytic
      formulas for the differential photon track length, are compared with EGS4
      calculations. Modifications to the analytic formulas are suggested. A scaling
      function is derived to estimate, from the thick-target formula, neutron yields
      produced in thin targets.

PMID- 8567289
TI  - An evaluation of ratio systems in radioecological studies.
AB  - Replicate samples of soil, Juncus squarrosus and Calluna vulgaris were taken
      within a grid system on an organic peatland soil site in Ireland. A similar
      sampling survey was carried out on an organic rich forest soil site in Sweden,
      where Vaccinium myrtillus and Vaccinium vitis-idaea with corresponding soil
      samples were taken within a Picea abies stand. The data were used to investigate
      the relationship between soil and plant 137Cs content and to examine the validity
      of using ratios to describe this relationship. Findings from both countries were
      in agreement. There were no significant changes in plant 137Cs concentration
      associated with increasing soil content. When data from both countries were
      merged and treated as a single data set, a significant overall positive
      correlation (95% confidence level) between soil and plant 137Cs levels was
      observed. Concentration ratios and transfer factors were calculated for 137Cs and
      40K uptake from soils to plants. Both ratio types exhibited a clearly defined
      decrease associated with increasing soil concentrations for both radionuclides.
      Findings demonstrate serious problems with the use of ratios for the evaluation
      of radionuclide transfer.

PMID- 8567290
TI  - Volume traps--a new retrospective radon monitor.
AB  - A new method to trace back average radon concentrations in dwellings over several
      decades in time has been developed. This retrospective radon monitor is based on
      the measurement of the alpha activity of 210Po deposited in volume traps, e.g.,
      spongy materials used for mattresses and cushions. Polyester samples with
      different densities have been exposed to radon-laden air. The exposures
      correspond to characteristic radon concentrations between 390 Bq m-3 and 3.9 kBq
      m-3 over a 20 y period. The precision in converting the 210Po-signal to the radon
      exposure has been improved by more than one order of magnitude compared to other
      common techniques. It is shown that this very sensitive method may be applied to
      almost all types of volume traps used in households.

PMID- 8567291
TI  - Analysis of models assessing the radionuclide migration from catchments to water
      bodies.
AB  - In this paper the analysis of models for assessing the migration of radioactive
      substances from catchments to water bodies was carried out. Comparisons are made
      between the mathematical form of the experimental dissolved radionuclide transfer
      functions (Transfer Function = the amount of radionuclide flowing per unit time
      from upstream drainage basin to a water body following a single-pulse deposition
      of radioactive substance) evaluated for rivers in Europe contaminated after the
      Chernobyl accident, with the "Green Functions" (Green Function = the radionuclide
      flow per unit time from catchment to water body calculated by the model as a
      result of a single-pulse input deposition) characterizing some of the most common
      models. Generally transfer functions are the sum of some time-dependent
      exponential components. The analysis showed that two main components (a short
      term and a long-term component) may be detected over a period of only a few years
      after the accident. The comparison of transfer functions and Green functions
      showed that a) models based on the traditional concept of kd (the radionuclide
      partition coefficient soil-water) do not explain the higher value of the
      experimental long-term effective-decay constant for 137Cs compared with 90Sr; and
      b) traditional models do not explain the nonlinear dependence of the flux (Bq s
      1) of dissolved 90Sr migrating through a catchment as a function of the water
      flux. A semi-empirical model was developed to give reason for the above effects.
      This model is based on phenomena of water saturation in different soil layers and
      on the nonreversible processes responsible for the non-availability to migration
      of radionuclides.

PMID- 8567292
TI  - Scatter radiation intensities about mammography units.
AB  - The intensity of scattered x rays about two clinically installed mammographic
      units was measured at 25, 30, and 35 kVp over a range of scattering angles. The
      scatter-to-primary ratio for backscattering is measured to be 4 to 7 times
      greater than that for 90 degrees scattering. The scatter fraction is the ratio of
      scatter dose at 1 m to primary dose at 1 m per primary x-ray field area. Averaged
      over various phantom and field sizes, the scatter fraction for mammography ranges
      from 0.01 x 10(-6) cm-2 to 0.2 x 10(-6) cm-2 at 0 degrees, approximately 0.25 x
      10(-6) cm-2 at 90 degrees, to 1.7 x 10(-6) cm-2 at 163 degrees, with not more
      than 30% difference between the scatter intensity generated at 25 and 35 kVp. The
      differences in the scatter fraction measured off two mammography units from two
      manufacturers are less than 10% for scattering angles greater than 45 degrees.
      However, the intensity of forward scatter depends strongly on the construction of
      the image receptor assembly and x-ray tube collimator, with a sharp rise in the
      scatter fraction at approximately 25 degrees for the 18 x 24 cm2 image receptor
      apparently due to scatter off the collimator. The dose (normalized at 1 m per 100
      patients) in directions toward adjacent walls, ceiling, and floor is
      conservatively calculated, providing a quick method for estimating the unshielded
      dose to an occupied area.

PMID- 8567293
TI  - A portable survey meter method for locating and quantifying removable
      contamination after 131I therapies.
AB  - Identifying 131I surface contamination and decontaminating the removable fraction
      from rooms where patients have received iodine therapies is a common task at many
      hospitals. The current regulatory preferred method for this task is wipe testing
      for removable contamination. The purpose of this paper is to evaluate the
      suitability of a sensitive survey meter for this task. Both methods and their
      detection systems are evaluated in the laboratory as well as in a clinical
      environment. The results indicate that the portable survey meter method is better
      at both locating and quantifying removable contamination. An additional benefit
      of the survey meter method is the ability to clean rooms promptly for
      reoccupancy.

PMID- 8567294
TI  - How to screen for 222Rn in large buildings.
AB  - 222Rn measurements have been made in over 10,000 ground-contact rooms in 908
      federal buildings. These data were examined statistically to compare parametric
      distributions that might be useful in the design and execution of future surveys
      of indoor 222Rn in large buildings. In 152 of the 365 buildings with the most
      measurements per building, the log-normal distribution was acceptable. Many other
      distributions were observed in the other 213 buildings, including bi- and tri
      modal distributions. In contrast, when data from entire facilities were examined,
      the data were usually described by a lognormal distribution. Because of the above
      observations, we propose that any future surveys of indoor 222Rn in large
      buildings be done in two phases, screening and assessment. During the screening
      phase, all facilities may be surveyed with a comparatively low sampling density,
      perhaps, one measurement per 465 m2 (5,000 ft2) of floor space. Based on the
      results presented here, it is expected that statistical analysis of the screening
      data will reveal any facilities with substantial evidence of a high incidence of
      rooms with elevated indoor 222Rn concentrations (e.g., above 150 Bq m-3). In the
      assessment phase, the identified facilities will be surveyed with a sampling
      density of one measurement for every ground-contact room or about one per 84 m2
      (900 ft2). Using numerical simulation techniques, we have tested the proposed
      screening phase protocol against data from sixteen facilities. The results of the
      simulated screenings support the feasibility of a two-phased approach to the task
      of identifying facilities having rooms with elevated 222Rn concentrations.

PMID- 8567295
TI  - Outdoor field evaluation of passive tritiated water vapor samplers at Canadian
      power reactor sites.
AB  - Tritium is one of several radioactive nuclides routinely monitored in and around
      CANDU (CANada Deuterium Uranium) power reactor facilities. Over the last ten
      years, passive samplers have replaced active sampling devices for sampling
      tritiated water vapor in the workplace at many CANDU stations. The potential of
      passive samplers for outdoor monitoring has also been realized. This paper
      presents the results of a 1-y field trial carried out at all five Canadian CANDU
      reactor sites. The results indicate that passive samplers can be used at most
      sampling locations to measure tritiated water vapor in air concentrations as low
      as 1 Bq m-3 over a 30-d sampling period. Only in one of the five sampling
      locations was poor agreement observed between active and passive monitoring data.
      This location, however, was very windy and it is suspected that the gusty winds
      were the source of the discrepancies observed.

PMID- 8567297
TI  - Counting geometry and its influence on thyroid monitoring.

PMID- 8567296
TI  - Radon, silicosis, and lung cancer.

PMID- 8567298
TI  - Remarks on the adsorption of radon from a humid atmosphere.

PMID- 8567299
TI  - External rewarming and age in mildly hypothermic patients after cardiac surgery.
AB  - OBJECTIVE: To compare the effects of two external rewarming methods on body core
      temperature and the rate of rewarming between two age groups (less than 65 years,
      65 years or more) of adult, mildly hypothermic patients who have undergone
      cardiac surgery, during the immediate postoperative period. DESIGN: Stratified,
      randomized clinical trial. SETTING: Five-bed cardiac surgical intensive care unit
      in a large teaching-research institution. SUBJECTS: Thirty-two white patients who
      had undergone cardiac surgery and who had mildly hypothermic body core
      temperatures (33 degrees to 35 degrees C) immediately after the surgery. OUTCOME
      MEASURES: Body core temperature was measured with a pulmonary artery catheter
      thermistor at the time of external rewarming method application and at 60, 90,
      and 150 minutes afterward. Rate of rewarming was measured as body core
      temperature change in degrees Celsius per hour (at 36.6 degrees C, minus body
      core temperature when external rewarming method was applied, divided by total
      rewarming time). Temperatures were recorded six times at intervals of 15 minutes;
      then every 30 minutes until a value of 36.6 degrees C was obtained, at which time
      the blanket was removed; then hourly for 8 hours. INTERVENTION: Either a fluid
      filled circulating blanket (active-conductive external rewarming) or a reflective
      blanket (passive-reflective external rewarming) was applied immediately after
      core temperature was measured on admission to the cardiac surgical intensive care
      unit after surgery. RESULTS: External rewarming methods affected body core
      temperature differently at different times, and there were significant
      differences in body core temperature across the time periods (p < 0.05). Both
      active and passive external rewarming methods showed a sigmoidal rewarming
      pattern without a downward temperature drift. The fluid-filled circulating
      blanket produced a quicker and steeper body core temperature change in the early
      rewarming phase; the reflective blanket resulted in a more gradual temperature
      rise. Age did not significantly affect body core temperature, nor did age or
      external rewarming method significantly influence the rate of rewarming, although
      total rewarming time was longer for those of more advanced age. Seven subjects
      with passive rewarming method experienced body core temperature overshoot during
      the 8-hour period after blanket removal. CONCLUSIONS: In this study, conduction
      and reflection of radiant heat were equally effective in producing an acceptable
      rate of rewarming but contributed to different internal patterns in core
      rewarming. The average total rewarming time with the active external rewarming
      method was 1 hour shorter than with the passive external rewarming method.

PMID- 8567300
TI  - Predictors of compliance with diet 6 months after heart transplantation.
AB  - OBJECTIVE: To examine and predict patient compliance with diet 6 months after
      heart transplantation. DESIGN: Prospective, correlational design, with nonrandom
      sample. SETTING: Midwestern and southern medical centers. PATIENTS: Ninety-four
      adult patients who had undergone heart transplantation 6 months previously (mean
      age 55 years; primarily married men). VARIABLES: Sixteen independent variables
      measured by nine instruments (with acceptable preliminary reliability and
      validity data) and chart review were used to predict compliance with diet 6
      months after heart transplantation. STATISTICS: Descriptive statistics,
      correlations, and multiple regression were used to analyze the data. RESULTS:
      More than 85% of patients were compliant with their diet most or all of the time,
      and more than 70% of patients experienced little or no difficulty complying with
      their diet. Difficulty with dietary compliance, gastrointestinal symptoms, and
      health perception predicted dietary compliance (accounting for 38% of variance).
      CONCLUSIONS: This study will contribute to enhanced patient care and may decrease
      morbidity and deaths after transplantation.

PMID- 8567301
TI  - Predictors of functioning of patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To determine the extent to which mood, symptoms, lung function, and
      social support of patients with chronic obstructive pulmonary disease (COPD)
      predicted their level of functioning over a 30-month period. DESIGN: Prospective,
      longitudinal. SETTING: The homes of patients living in or adjacent to
      metropolitan Toronto. SUBJECTS: Seventy-one patients (48 men and 23 women) with
      COPD who had a forced expiratory volume in 1 second less than 50% of predicted
      (FEV1 < 50%) and who spoke English. They ranged in age from 43 to 81 years (mean
      66.37 years). OUTCOME MEASURES: The patients' level of functioning at the final
      data collection visit, 30 months after the initial measure. INSTRUMENTS: At both
      data collection visits patients completed measures of mood (negative mood scales
      of the Profile of Mood States), symptoms (Bronchitis-Emphysema Symptom
      Checklist), social support (Personal Resource Questionnaire), and functioning
      (Sickness Impact Profile). RESULTS: Data were analyzed by use of multiple
      regression analysis. From measures taken at the initial visit (T1), the best
      predictors of patients' functioning at 30 months (T2) were their functioning at
      T1, symptoms, FEV1, and age. Together these accounted for 70% of the variance in
      the final functioning scores, with initial functioning scores accounting for 51%
      of the variance. The most prevalent symptoms were dyspnea and fatigue, and both
      were highly correlated with functioning scores 30 months later. CONCLUSIONS: In
      this study, symptoms, FEV1, and age are predictive of functioning in patients
      with COPD over a 30-month time frame. However, only 50% of the 143 patients
      recruited into the study completed it. Therefore caution needs to be exercised
      when the results are applied to other patients with COPD.

PMID- 8567302
TI  - Reduction of noise levels in intensive care units for infants: evaluation of an
      intervention program.
AB  - OBJECTIVE: To investigate whether educational information for nurses concerning
      causes of noise would decrease noise levels in an intensive care unit for term
      newborns and infants. DESIGN: Pretest and posttest. SETTING: Children's surgical
      ward in a university hospital in southern Sweden. SUBJECTS: Fifty-two nurses in
      the surgical ward. OUTCOME MEASURES: Noise levels. INTERVENTION: An educational
      program consisting of a presentation of a videotape, presentation of the decibel
      values for various care activities, and a discussion of the problem. RESULTS:
      Statistical analysis with a paired two-tailed t test showed significant
      differences to exist between measurements in a cot and an incubator before the
      intervention (p = 0.0001), and between cot measurements before and after the
      intervention program (p = 0.0007). CONCLUSIONS: The results of this study show
      that through simple methods and without additional costs, and by making the staff
      aware of the problem, noise levels can be lowered considerably.

PMID- 8567303
TI  - Treatment of sepsis and septic shock: a review.
AB  - Septic shock is one of the leading causes of death in intensive care units, and
      its incidence is increasing. Mortality rates as high as 95% are reported, with
      rates of 60% or more even when diagnosed and treated promptly. This review
      examines the definition of septic shock, its pathogenesis, and supportive
      therapy, with particular attention to intervention during the septic shock
      cascade.

PMID- 8567305
TI  - Stressors experienced by nurses while caring for organ donors and their families.
AB  - OBJECTIVES: To identify the stressors experienced by nurses who care for organ
      donors and their families. DESIGN: Retrospective, exploratory, descriptive.
      SETTING: Eastern Canada. PARTICIPANTS: Seventeen nurses who worked in a
      neurologic intensive care unit were interviewed. All had provided care to organ
      donors. RESULTS: The threat of the patient dying, the inconsistent commitment of
      physicians to organ donation, and returning to an empty space were frequently
      mentioned stressors. All nurses felt positive about being involved in the organ
      donation process. CONCLUSION: To deal with the stressors, nurses recommended more
      education in the area of grief, crisis interventions, stress, and coping
      theories. More important, they suggested the need to address their feelings
      through stress debriefing sessions.

PMID- 8567304
TI  - Critical care nursing education at the baccalaureate level: study of employment
      and job satisfaction.
AB  - OBJECTIVE: To examine the employment patterns of nurses who completed an
      undergraduate course in critical care nursing (CCN); examine the impact of the
      course on job satisfaction; and compare the job satisfaction of critical care
      nurses who completed a course at the baccalaureate level and a control group of
      nurses in critical care who did not have these educational experiences. DESIGN:
      Descriptive. SETTING: Ten hospitals in the midwest in which graduates of a CCN
      course at the BSN level were in practice. SUBJECTS: There were two groups of
      participants: 42 nurses prepared at the undergraduate level for critical care and
      59 critical care nurses from the same units. OUTCOME MEASURES: Employment
      patterns and job satisfaction measured by Stamps and Piedmonte's Index of Work
      Satisfaction instrument. RESULTS: Most (n = 33, 78.6%) graduates entered critical
      care as their first position in nursing. At the time of follow-up, these
      graduates remained in CCN practice. The findings suggested that completion of an
      undergraduate course enabled students to enter critical care as new graduates.
      Results of a Mann-Whitney U test indicated no differences in job satisfaction
      between nurses who remained in critical care and those practicing in non-critical
      care units. There were no significant differences in total job satisfaction or in
      any of its component scores between graduates of the course and the control group
      of critical care nurses. Both groups were least satisfied with pay and most
      satisfied with their interactions with others on the unit. CONCLUSIONS: Although
      educational experiences in critical care at the undergraduate level did not
      influence job satisfaction, other benefits of this education were suggested by
      the findings. Completion of an undergraduate CCN course enabled graduates to
      enter critical care as their first practice position.

PMID- 8567306
TI  - Expert nursing behaviors in care of the dying adult in the intensive care unit.
AB  - OBJECTIVE: To identify expert nursing behaviors in care of the dying adult in the
      intensive care unit. DESIGN: Descriptive, exploratory. SETTING: One tertiary care
      hospital surgical intensive care unit and one community hospital medical-surgical
      intensive care unit in a western Canadian city. SUBJECTS: Ten intensive care
      nurses nominated as experts in the care of dying adults by their peers. RESULTS:
      Behaviors identified after constant comparative content analysis of transcribed
      interviews with nurse experts included: responding after death has occurred;
      responding to the family; responding to anger; responding to colleagues;
      providing comfort care; and enhancing personal growth. CONCLUSIONS: The
      identification and description of specific nursing interventions in care of the
      dying are imperative to demonstrate to practicing clinicians that a clearly
      defined role exists for them in the delivery of terminal care.

PMID- 8567307
TI  - Intravenous site care practices in critical care: a national survey.
AB  - OBJECTIVE: To collect and compare written procedures for central line intravenous
      site care. DESIGN: Descriptive, stratified, random sample survey. SETTING: Adult
      medical-surgical critical care units among hospitals throughout the United
      States. SAMPLE: One hundred fifty-two returned surveys. RESULTS: A 24.6% response
      rate with underrepresentation from smaller institutions and hospitals in the Mid
      Atlantic and West South Central regions of the country. There were wide
      variations in procedures for intravenous site care related to type of dressing
      used and frequency of dressing changes. CONCLUSIONS: Standardization of catheter
      care is needed to ensure consistent quality of intravenous site care. Lack of
      standardization may be due to lack of a research data base linking various
      components of care to outcomes such as infection, patient comfort, or catheter
      retention.

PMID- 8567308
TI  - Nonrheumatic poststreptococcal myocarditis.

PMID- 8567309
TI  - TB engineering controls: mobile high-efficiency-filter air cleaners.

PMID- 8567310
TI  - Small parts dislodgment from Binky Lil'Bink newborn pacifiers.

PMID- 8567311
TI  - Inadvertent battery operation of 3M Sarns Delphin centrifugal pump.

PMID- 8567312
TI  - Material degradation of angiographic catheters.

PMID- 8567313
TI  - Risk of ineffective assisted ventilation using fenestrated tracheostomy tubes
      equipped with 15 mm connectors.

PMID- 8567314
TI  - DT-diaphorase as a target enzyme for biochemical modulation of mitomycin C.
AB  - We studied a selective enhancement of the mitomycin C (MMC)-induced antitumor
      effect focusing on the intracellular metabolism by NAD(P)H:quinone oxidoreductase
      (DT-diaphorase, DTD). The level of cellular DTD activity related well to the
      degree of MMC-induced DNA total cross links and cell growth inhibition in human
      cancer cell lines, KB, PH101, SH101 and K562. A DTD inhibitor, dicoumarol (DIC)
      or flavin adenine dinucleotide (FAD), inhibited the MMC-induced DNA damage and
      cytotoxicity at a non-toxic concentration. The DTD-mediated MMC activation was pH
      dependent, and highest at pH 6 and lowest at pH 8. Although an inverse
      relationship appeared to exist between DTD activity and MMC efficacy in human
      xenografts implanted into nude mice and 9 fresh human tumor specimens, the
      investigation in 3 culture cells, HEC-46, HCC-48 and HCC-50, established from
      those xenografts, showed that DTD activated MMC in a pH-dependent manner as well
      as the other cell lines. Significant tumor pH reduction from 7.1 to 6.7 by
      continuous glucose infusion also increased the MMC-induced tumor growth
      inhibition in the human tumor xenografts. Thus, we conclude that bioreductive
      activation by DTD in a pH-dependent manner may be of key importance in the MMC
      induced antitumor effect and that an increased MMC efficacy at a reduced pH
      caused by hyperglycemia may be applied to clinical use as a new manipulation for
      a biochemical modulation of MMC.

PMID- 8567315
TI  - Lipoprotein(a) and other risk factors for cerebral infarction.
AB  - The serum concentration of lipoprotein(a) [Lp(a)], lipids, lipoproteins,
      apolipoprotein A-I, and apolipoprotein B were determined in 228 patients with
      cerebral infarction, composed of 87 cases of asymptomatic lacunar infarction, 99
      cases of lacunar infarction, and 42 cases of atherothrombotic infarction, and in
      a control group of 138 healthy subjects with normal MRI. Observations were made
      on the distribution of Lp(a), Lp(a) and other risk factors for cerebral
      infarction and these were statistically analyzed, primarily by multiple logistic
      regression analysis. The diagnosis of these cases was based on the Classification
      of Cerebrovascular Diseases III of the National Institute of Neurological
      Disorders and Stroke. The following results were obtained. 1) Lipoprotein (a) (1)
      Lp(a) did not show a normal distribution with the curve showing a gradual
      declining slope to the right. It was therefore considered not appropriate in our
      analysis to use as a means or standard deviation. (2) The 25th percentile, 50th
      percentile, and 75th percentile of the control group were 5.0 mg/dl, 11.0 mg/dl,
      and 22.4 mg/dl, respectively. In studying the distribution in these percentile
      ranges by subtypes of infarction, an increase in cases showing values greater
      than the median of the control group was observed in asymptomatic lacunar
      infarction, lacunar infarction, and atherothrombotic infarction, when compared to
      the control group. In asymptomatic lacunar infarction and lacunar infarction in
      particular, Lp(a) showed a significantly higher value compared to the control
      group. (3) However, by multiple logistic regression analysis to adjust for age
      and sex, Lp(a) did not show a significant odds ratio for asymptomatic lacunar
      infarction, lacunar infarction and atherothrombotic infarction. 2) Various serum
      lipids and other parameters (1) The various serum lipids did not show any
      involvement in asymptomatic lacunar infarction. However, involvement of HDLC and
      Apo A-I in lacunar infarction and atherothrombotic infarction was observed with
      the odds ratios in lacunar infarction being 4.2 with a confidence interval of 2.9
      9.4 and 4.7 with a confidence interval of 2.2-10.1, and the odds ratios in
      atherothrombotic infarction being 3.1 with a confidence interval of 1.1-9.0 and
      9.6 with a confidence interval of 3.0-30.5, respectively. (2) Involvement of
      diabetes mellitus in asymptomatic lacunar infarction and lacunar infarction was
      small, but a strong involvement in atherothrombotic infarction was observed with
      the odds ratio being 4.3 with a confidence interval of 1.2-16.2. (3) Involvement
      of hypertension in asymptomatic lacunar infarction and lacunar infarction was
      observed with the odds ratios being 2.6 with a confidence interval of 1.4-5.2 and
      5.6 with a confidence interval of 2.4-13.0, respectively, but the involvement in
      atherothrombotic infarction was low. The foregoing results indicated that there
      was no involvement of Lp(a) as a risk factor for any type of cerebral infarction,
      unlike its involvement in coronary heart diseases. Only blood pressure was
      involved as a risk factor for asymptomatic lacunar infarction, but for lacunar
      infarction not only blood pressure but also HDLC and Apo A-I were involved as
      risk factors. HDLC, Apo A-I, and diabetes mellitus were involved as risk factors
      for atherothrombotic infarction, but the involvement of hypertension was minimal.

PMID- 8567316
TI  - The relationship between gastric secretion and type of early gastric carcinoma.
AB  - To determine the relationship between gastric secretion and gastric carcinoma, we
      investigated gastric acid secretion and the fasting serum levels of pepsinogen I
      and gastrin in 50 Japanese patients with early gastric carcinoma. After the
      histological and macroscopic type of carcinoma had been determined, results were
      compared with findings in 50 Japanese control subjects whose gastric mucosa was
      endoscopically normal. The maximum gastric acid secretion and fasting levels of
      serum pepsinogen I were significantly lower in intestinal type gastric carcinoma
      than in diffuse type carcinoma and in the controls. They were also significantly
      lower in the non-ulcerative (elevated or flat) type than in the ulcerative
      (depressed) type of carcinoma. The serum gastrin levels in patients with early
      gastric carcinoma of either the intestinal or diffuse type were higher than those
      in the control subjects, though the difference was not significant. Gastric acid
      secretion and serum pepsinogen I levels were related with both the histological
      and macroscopic types of gastric carcinoma. These findings suggest that the serum
      pepsinogen I level might be useful as a maker for early gastric carcinoma of the
      intestinal type.

PMID- 8567317
TI  - Renal osteodystrophy in hemodialysis patients.
AB  - Patterns of bone loss in the axial and appendicular skeleton were studied in 88
      chronic hemodialysis patients (59 males and 29 females) and 60 normal volunteers
      (30 males and 30 females). The hemodialysis patients were properly medicated with
      phosphate binders and 1 alpha-OH D3 where necessary. The metacarpal index (MCI),
      sigma gray scale/diameter (sigma GS/D) and bone mineral content (BMC) were
      measured as bone mass indices, and the relationship investigated between clinical
      factors [age, duration of hemodialysis, serum phosphate (P), calcium (Ca),
      carboxy-terminal fragments of parathyroid hormone (C-PTH), osteocalcin (OC),
      alkaline phosphate (ALP) and Ca x P]. The bone loss in the hemodialysis patients
      was greater than that in the normal controls and was accelerated after menopause
      in women. However, the bone mass indices in a few of the hemodialysis patients of
      advanced age (over 60) showed higher values than those of the controls. The bone
      mass indices in male hemodialysis patients showed a negative correlation with the
      hemodialysis duration, C-PTH and OC, as did those in female patients with
      hemodialysis duration. On the other hand, BMC in female hemodialysis patients
      showed a negative correlation with P, C-PTH and Ca x P. In conclusion, age and
      the duration of hemodialysis are the most essential factors in skeletal and
      trabecular bone loss in male and female hemodialysis patients. Subsequent factors
      responsible for skeletal bone loss in male patients are C-PTH and OC, and those
      for trabecular bone loss in female patients are P, C-PTH and Ca x P. Control of
      the levels of C-PTH, OC, P and Ca x P is recommended for prevention of bone loss
      in hemodialysis patients.

PMID- 8567318
TI  - Membrane based ethanol separation process.

PMID- 8567319
TI  - New trends in downstream processing of biotechnological products.

PMID- 8567320
TI  - Membrane separations in biotechnology.

PMID- 8567321
TI  - Expanded bed chromatography and radial flow column chromatography: the approaches
      for adsorption chromatography of biomolecules on industrial scale.
AB  - Adsorption of proteins directly from unclarified feed-stocks, has gained
      importance in the recovery of biomolecules on Industrial scale. Adsorption in
      expanded beds and radial flow gives significantly better results compared to
      conventional column chromatography methods for downstream processing of variety
      of proteins from particulate-containing feed-stocks, such as fermentation broths
      and cells extracts. The simple operation of these techniques reduces the
      complexity of downstream processing by eliminating steps such as filtration,
      centrifugation and concentration. One step purification, with simple equipment,
      these techniques enable to recover pure protein with 95% yield in
      biotechnological industry. The principles, operating procedures, adsorbents and
      applications of these techniques are discussed.

PMID- 8567322
TI  - Ultrafiltration membranes in biotechnology.

PMID- 8567323
TI  - Bioprocess technology with special emphasis on downstream processing--a relevant
      education to industry's needs.

PMID- 8567324
TI  - Downstream processing of sucrose 6-glucosylmutase and production of isomaltulose,
      a non-cariogenic, low-caloric sweetener.

PMID- 8567325
TI  - Developments and newer approaches in downstream processing of biopharmaceuticals.

PMID- 8567326
TI  - Application of innovative downstream processing techniques in isolation and
      purification of biomolecules.

PMID- 8567327
TI  - External radiotherapy for carcinoma of the eyelid: report of 850 cases treated.
AB  - PURPOSE: We report a retrospective series of 850 patients treated by external
      irradiation for carcinoma of the eyelid at Institut Curie and we compare our
      results with other techniques: brachytherapy and surgery. METHODS AND MATERIALS:
      Eight hundred fifty patients were treated by external radiotherapy for carcinoma
      of the eyelid. None of these patients have been previously treated. All the
      patients were classified according to the TNM classification of (UICC). We
      distinguished five histological types and five clinical groups according to the
      site of the skin tumor. Three modalities of external radiotherapy were used:
      contact therapy, conventional radiotherapy, and electrontherapy. We reviewed the
      clinical files of the 850 patients who went regularly at follow-up visits.
      RESULTS: We report the 5-year survival results--alive with no evidence of
      disease: 72%; alive with progression: 2%; died from tumor progression: 0.5%; died
      from intercurrent disease: 19.5%; and lost to follow-up: 5%. The 5-year local
      control rate was 97.5%. We observed 45 failures--lymph node, metastatic, and
      local--and emphasize this last group by presenting the results of treatment of
      these local failures. We studied the complications of treatment: 2.3% of corneal
      complications, 2% of cataracts, and 1.4% of serious ocular complications.
      CONCLUSIONS: Our results concerning local failures and loss of the eye are
      comparable to those reported for other techniques involving brachytherapy or
      surgery. Overall, external radiotherapy is a safe and effective treatment, as it
      ensures a high local control rate and provides perfectly satisfactory functional
      and esthetic results. It seemed particularly useful to report this series in that
      few publications are available on this subject that, nevertheless, constitutes a
      topical issue.

PMID- 8567328
TI  - Oropharyngeal carcinoma treated with radiotherapy: a 30-year experience.
AB  - PURPOSE: This study was done to determine the outcome in patients with
      oropharyngeal carcinoma treated at the University of Florida with radiotherapy
      alone to the primary site, for comparison with reported results of other types of
      treatment. METHODS AND MATERIALS: Of a consecutive cohort of 785 patients with
      biopsy-proven, previously untreated, invasive squamous cell carcinoma of the
      oropharynx, this report is based on the 490 patients who had continuous-course
      irradiation with curative intent at the University of Florida between October
      1964 and January 1991. All patients had a minimum 2-year follow-up. Forty-eight
      percent had Stage T3 or T4 disease, and 64% had clinically apparent neck node
      metastases. The median radiation dose was 68 Gy for once-a-day treatment and 76.8
      Gy for twice-a-day treatment. Patients with advanced neck node disease had
      planned neck dissection(s) after radiotherapy. RESULTS: The overall local control
      rate after radiotherapy alone was 73%. The ultimate local control rate (including
      surgical salvage) was 78%. At 5 years, the probability of control of neck disease
      was 85%; control above the clavicles, 67%; absolute survival, 44%; cause-specific
      survival, 77%; distant metastasis (as the first or only site of failure), 11%.
      Thirteen patients (2.6%) experienced severe treatment complications. CONCLUSION:
      Radiotherapy results in tumor control and survival rates comparable with rates
      achieved with combined irradiation and surgery, with less morbidity.

PMID- 8567329
TI  - Local irradiation alone for peripheral stage I lung cancer: could we omit the
      elective regional nodal irradiation?
AB  - PURPOSE: The results of local irradiation only for patients with Stage I lung
      cancer were analyzed to see whether the treatment of regional lymph nodes could
      be omitted. METHODS AND MATERIALS: One hundred and eight medically inoperable
      patients with nonsmall cell lung cancer (T1 and peripheral T2) were treated with
      60 Gy split course or 65 Gy continuous treatment. The target volume included the
      primary tumor only, without regional lymph nodes. Response, survival, and
      patterns of failure were analyzed. RESULTS: The overall response rate was 85%
      with 50 (46%) complete responses (CRs). Overall survival at 3 and 5 years was 31
      and 15%, and cancer-specific survival was 42 and 31% at 3 and 5 years,
      respectively. The actuarial 5 years local relapse free survival in patients with
      a CR was 52%. Tumor size (< or = 4 cm) was strongly correlated with the chance of
      complete remission and better survival. Of patients in complete remission, only
      two had a regional recurrence as the only site of relapse; an additional two
      patients had a locoregional recurrence. CONCLUSION: High-dose local radiotherapy
      on the primary tumor only is justified for medically inoperable patients with
      peripherally located nonsmall lung cancer. The low regional relapse rate does not
      support the need for the use of large fields encompassing regional lymph nodes.
      Using small target volumes, higher doses can be given and better local control
      rates can be expected.

PMID- 8567330
TI  - Effect of interfraction interval in hyperfractionated radiotherapy with or
      without concurrent chemotherapy for stage III nonsmall cell lung cancer.
AB  - PURPOSE: To explore the influence of interfraction interval in hyperfractionated
      radiotherapy (HFX RT) with or without concurrent chemotherapy for Stage III
      nonsmall cell lung cancer. METHODS AND MATERIALS: One hundred sixty-nine patients
      treated in a randomized study were retrospectively analyzed. Group I patients
      were treated by HFX RT with 1.2 Gy twice daily with a total dose of 64.8 Gy in 27
      treatment days, while Groups II and III patients were treated by the same HFX RT
      and concurrent chemotherapy with carboplatin and etoposide (every week in Group
      II and every other week in Group III). Interfraction intervals of either 4.5-5 h
      or 5.5-6 h were used for each patient. RESULTS: Patients treated with shorter
      interfraction intervals (4.5-5 h) had a better prognosis than those treated with
      longer intervals (5.5-6 h) (median survival: 22 vs. 7 months; 5-year survival
      rate: 27% vs. 0%, p = 0.00000). This phenomenon was observed in all treatment
      groups. Patients > or = 60 years of age, with Stage IIIA disease, or with
      previous weight loss < or = 5% were treated more often with the shorter intervals
      than those < 60 years, with Stage IIIB disease, or with weight loss > 5%,
      respectively, but in all of these subgroups of patients, the shorter intervals
      were associated with a better prognosis. Multivariate analysis showed that the
      interfraction interval was an independent prognostic factor, together with sex,
      age, performance status, and stage. The shorter intervals were associated with an
      increased incidence of acute high grade toxicity, but not with an increase in
      late toxicity. CONCLUSION: Patients treated with shorter interfraction intervals
      (4.5-5 h) appeared to have a better survival than those treated with longer
      intervals (5.5-6 h). Prospective randomized studies are warranted to further
      investigate the influence of interfraction interval in HFX RT.

PMID- 8567331
TI  - Prospective trial of combined hyperfractionated radiotherapy and bronchial
      arterial infusion of chemotherapy for locally advanced nonsmall cell lung cancer.
AB  - PURPOSE: This article is a prospective trial of hyperfractional radiotherapy with
      bronchial arterial infusion of anticancer drugs to treat locally advanced
      bronchogenic cancer. The treatment results, the complications of bronchial
      arterial infusion, the failure patterns, the relationship of technical aspects of
      delivery of radiotherapy, and the protocol of anticancer drugs are presented.
      METHODS AND MATERIALS: One hundred and twenty-six patients with locally advanced
      bronchogenic cancer, treated from January 1988 to January 1990, were divided
      randomly into four groups in our hospital. Group 1: combination of
      hyperfractional radiotherapy with bronchial arterial infusion of anticancer drugs
      (30 cases); Group 2: combination of conventional radiotherapy with bronchial
      arterial infusion of anticancer (33 cases); Group 3: combination of systemic
      chemotherapy and split-course radiotherapy (33 cases); Group 4: conventional
      radiotherapy only (30 cases). RESULTS: All the patients were followed for 3
      years. The 1-year survival rates for Groups 1, 2, 3, and 4 are 80, 63.6, 48.5,
      and 30%, respectively. The 2-year survival rates for Groups 1, 2, 3, and 4 are
      23.3, 15.15, 9.1, and 6.6%, respectively. The 3-year survival rates for Groups 1,
      2, 3, and 4 are 10, 3.3, 0, and 0%, respectively. CONCLUSION: This study
      demonstrated that the combination of hyperfractional radiotherapy with bronchial
      arterial infusion anticancer drugs can be performed safely and effectively for
      locally advanced bronchogenic carcinoma.

PMID- 8567332
TI  - The impact of overall treatment time on the results of radiotherapy for nonsmall
      cell lung carcinoma.
AB  - PURPOSE: We evaluated the impact of overall treatment time on the disease-free
      survival (DFS) and local control after radiotherapy for nonsmall cell lung
      carcinoma. METHODS AND MATERIALS: One hundred fifty-three cases considered as
      responders to radiotherapy were retrospectively analyzed. Patients with Karnofsky
      status < 70, pretreated with chemotherapy and with pleural or pericardial
      effusion, were excluded from the analysis. Radiation dose homogenization was done
      with calculation of the normalized total dose without (NTD) and with time
      correction (NTD-T) for alpha/beta = 10 Gy. RESULTS: Kaplan-Meier curves for 2
      year DFS showed that any analysis based on radiation dose can prove to be
      erroneous when the time factor is neglected. Although there was no difference
      between the 47-55 Gy and 56-64 Gy NTD groups, a log rank test revealed a strong
      difference (p < 0.0002) between NTD-T groups. No difference was observed for
      patients with mediastinal involvement. Logistic regression analysis showed a
      statistical association of dose on 2-year local progression-free probability for
      different time compartments. For those cases without mediastinal involvement, the
      daily dose lost because of treatment protraction beyond 20 days after the
      beginning of radiotherapy was estimated to 0.2 Gy/day. When all cases were
      considered together this was calculated to 0.45 Gy/day. CONCLUSION: Time factor
      should not be underestimated when evaluating the results of radiotherapy for
      nonsmall cell lung cancer. There is strong evidence that prolonged overall
      treatment time could be a major cause of the failure of radiotherapy to control
      the local disease.

PMID- 8567333
TI  - P53 overexpression in head and neck carcinoma and radiotherapy results.
AB  - PURPOSE: P53 gene mutations are the common genetic changes encountered in human
      cancers, and there is extensive evidence that the P53 status may determine tumor
      response to therapy. This study was carried out to investigate whether there is
      any correlation between accumulation (overexpression) of P53 protein and poor
      prognosis in patients with head and neck carcinomas treated with radical
      radiotherapy. METHODS AND MATERIALS: Seventy-nine patients with head and neck
      carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy
      were studied retrospectively. Paraffin sections from archival material were
      studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies
      (D0-7) to human P53 protein. Univariate and multivariate analysis of loco
      regional tumor control and patient survival were performed on possible prognostic
      factors. RESULTS: Forty-two (53%) patients showed positive IHC staining in their
      tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43%
      of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with
      vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The
      proportion of tumor-stained nuclei was higher in the poorly differentiated than
      in the well and moderately differentiated tumors (p < 0.05), but there was no
      correlation with the patient overall or disease-free 5-year actuarial survival.
      There was no difference in the 5-year actuarial survival and disease-free
      survival between patients with P53 immunostaining in their tumors and those with
      no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor
      stage was the most significant prognostic factor with 5-year actuarial survival
      of 87% for early and 14% for late stages (p << 0.0001). There was a significant
      correlation between immunostaining and history of smoking (p = 0.02). CONCLUSION:
      The data demonstrate that the P53 accumulation as detected by immunohistochemical
      staining in a group of head and neck carcinomas was not predictive of patient's
      poor survival or disease-free survival. Multivariate statistical analysis showed
      that the TNM tumor stage was the only significant prognostic factor. There was a
      significant association between P53 accumulation and smoking.

PMID- 8567334
TI  - An analysis of mandibular bone complications in radiotherapy for T1 and T2
      carcinoma of the oral tongue.
AB  - PURPOSE: To examine the incidence of mandibular bone complication in patients who
      underwent radiotherapy for T1 and T2 carcinomas of the oral tongue and to analyze
      the factors contributing to its occurrence. METHODS AND MATERIALS: The clinical
      records of 148 patients with T1 and T2 carcinoma of the oral tongue treated with
      radiotherapy alone between 1978 and 1989 were examined retrospectively.
      Interstitial brachytherapy, used as the major treatment modality, was performed
      using cobalt needles, radium needles, or iridium hairpins. The prescribed dose at
      the plane 5 mm from the plane of the radioactive sources was 65-70 Gy in
      interstitial brachytherapy alone, and 50-60 Gy in the combined treatment with
      external irradiation. An external irradiation dose of 30 Gy was usually used.
      RESULTS: Eleven of the patients showed radiation-induced mandibular bone
      complication. Two (1 T1, 1 T2) had been treated with interstitial brachytherapy
      alone, and nine (2 T1, 7 T2) with the combination of external irradiation and
      interstitial brachytherapy. The incidence of radiation complication of bone was
      significantly higher in the patients with T2 tumors (p = 0.04) and in those who
      received the combined treatment (p < 0.01). Multivariate analysis revealed that
      the total dose (p = 0.04) and dose rate of interstitial brachytherapy (p = 0.03)
      were significant factors contributing to radiation bone complication. A
      significant difference in the incidence of bone complication was also seen
      between patients who received a total dose of 90 Gy or more and those who
      received less than 90 Gy (p < 0.01), as well as between patients who were treated
      with 0.55 Gy/h or higher and those who were treated with less than 0.55 Gy/h (p =
      0.03). CONCLUSION: A significant increase in the incidence of bone complication
      was found at the total dose of 90 Gy or more and at the dose rate of 0.55 Gy/h or
      higher. In combined treatment with external irradiation and interstitial
      brachytherapy, the interstitial brachytherapy dose of 60 Gy appears to be the
      threshold at which mandibular bone complication is induced when the external
      irradiation dose is 30 Gy.

PMID- 8567335
TI  - P53-mediated radioresistance does not correlate with metastatic potential in
      tumorigenic rat embryo cell lines following oncogene transfection.
AB  - PURPOSE: Changes in wild-type p53 protein function occur in the majority of human
      tumors, and may alter genomic stability and the cellular response to ionizing
      radiation. Whether oncoproteins can render tumor cells both radioresistant and
      metastatic, may have implications for clinical strategies designed to improve
      local tumor control. In the studies reported here, we tested the hypothesis that
      acquired radioresistance correlates with metastatic potential within a large
      panel of transformed rat embryo cell (REF) lines following transfection with
      activated H-ras, mutant p53, and HPV16-E7 alleles. METHODS AND MATERIALS: Rat
      embryo cells (REF cells) were transfected using the calcium-phosphate technique
      with an activated H-ras gene alone, or in combination with human papillomavirus
      HPV16-E7 and/or human or murine mutant p53 sequences. Other rat embryo cell
      clones expressing transfected HPV-E7 and activated ras sequences subsequently
      acquired endogenous p53 gene mutations during culture in vitro. The relative
      expression of p21ras and p53 protein for each REF transformant was determined by
      Western blot analysis following transfection. REF clones were phenotypically
      characterized at early passage (i.e., passages 5-7) and late passage (i.e.,
      passages 10-20) for their: (a) relative tumor growth rate, and (b) their ability
      to undergo spontaneous metastasis following intramuscular injection into the hind
      legs of SCID mice. In vivo phenotypic end points were then compared to previously
      measured parameters of in vitro radiosensitivity for each cell line.
      Additionally, the expression of the cellular protease, plasminogen activator, was
      determined for a number of metastatic and nonmetastatic cell lines. RESULTS: We
      found no evidence that selected oncogene-transfected REF transformants that were
      radioresistant in culture had a greater spontaneous metastatic potential than
      nonradioresistant REF transformants. Neither the level of expression of the
      p21ras protein nor that of the p53 protein was correlated with the spontaneous
      metastatic phenotype when tested at early passage. The metastatic phenotype
      appeared to be independent of p53 genotype. The majority of metastatic REF clones
      tested (7 out of 9 clones) expressed plasminogen activator following oncogene
      transfection, in contrast to nonmetastatic REF transformed cell lines.
      CONCLUSIONS: Our results suggest that (a) intrinsic radioresistance does not
      correlate with spontaneous metastatic potential in oncogene-expressing REF
      transformant cell lines, and (b), novel clinical strategies designed to overcome
      oncogene-mediated radioresistance could potentially impact on overall survival,
      as gains in local tumor control may not be offset by a greater risk of distant
      metastasis.

PMID- 8567336
TI  - Carbogen and nicotinamide as radiosensitizers in a murine mammary carcinoma using
      conventional and accelerated radiotherapy.
AB  - PURPOSE: To compare the radiosensitivity of mouse tumors treated in air with
      conventional and accelerated radiotherapy with that of tumors treated in carbogen
      alone or carbogen combined with nicotinamide. METHODS AND MATERIALS: CaNT mammary
      tumors were irradiated with either 30 x-ray fractions in 6 weeks or 40 fractions
      in 26 days in air, carbogen alone, or carbogen combined with 120 mg/kg of
      nicotinamide (NAM), the latter given intraperitonealy 30 min before each
      fraction. The response to treatment was assessed using local control, weight
      loss, and metastasis-free survival. RESULTS: Both carbogen and carbogen plus
      nicotinamide significantly increased tumor radiosensitivity; enhancement ratios
      (ERs) in the 6-week regimen were similar to those seen in the accelerated
      schedule. The majority of the effect was achieved by carbogen alone but the
      addition of NAM further enhanced tumor radiosensitization (ERs of 1.5 and 1.4 for
      carbogen in the conventional and accelerated schedule, respectively, were
      significantly lower than ERs of 1.7 and 1.6 obtained with carbogen plus
      nicotinamide; p < or = 0.005). Treatment protraction significantly increased
      radioresistance, especially when tumors were treated under air. An extra 1.5 Gy
      per day was required in air to counterbalance proliferation; in carbogen alone
      and carbogen plus nicotinamide a dose loss of 0.9 and 0.6 Gy per day was
      observed, respectively. Compared with treatments in air alone delivered in 6
      weeks, acceleration of treatment combined with carbogen and nicotinamide gave the
      greatest increase in tumor radiosensitization (ER = 1.9). No toxic side effects
      and no detrimental changes in body weight were encountered when the sensitizers
      were administered 30 times (one fraction per day) or 40 times (two fractions per
      day). In both regimens, the incidence of metastases in mice treated with carbogen
      or carbogen plus nicotinamide was similar to that seen in animals treated in air.
      There was, however, a nonsignificant trend of a higher proportion of mice with
      metastasis in the accelerated schedule compared with the 6-week schedule.
      CONCLUSIONS: In both conventional and accelerated experimental radiotherapy,
      carbogen alone or combined with a small clinically relevant dose of NAM were well
      tolerated, achieved large and significant increases in radiosensitization, and
      did not affect the incidence of metastases. The sparing of damage, resulting from
      extending the overall treatment time, was less when the sensitizers were
      administered than when irradiations were performed in air. The study suggests
      that clinical radiotherapy regimens, which aim to reduce hypoxic and/or tumor
      clonogen proliferation, would benefit from the use of carbogen, especially if the
      gas is combined with nicotinamide and treatment acceleration.

PMID- 8567337
TI  - Effect of cisplatin on the clinically relevant radiosensitivity of human cervical
      carcinoma cell lines.
AB  - PURPOSE: To evaluate the effect of clinically relevant levels of cisplatin on the
      radiosensitivity of human cervical tumor cells, and to estimate what changes in
      local control rates might be expected to accrue from the concomitant use of
      cisplatin during fractionated radiotherapy. METHODS AND MATERIALS: The effects of
      concomitant cisplatin (1 microgram/ml, a typical intratumor concentration) on the
      clinically relevant radiosensitivity, i.e., surviving fraction after 2 G (SF2)
      values, was determined in 19 cloned human cervical tumor cell lines. These early
      passage cell lines had SF2 values ranging from 0.26 to 0.87. RESULTS: The
      concomitant administration of cisplatin reduced the clinically relevant
      radiosensitivity in the majority (11 out of 19) of the human tumor cell lines
      investigated. In only 4 out of 19 was any radiosensitization observed, and in 4
      out of 19 cell lines there was no significant change in radiosensitivity.
      However, the sum of the independent cell killing by radiation and cisplatin, was
      approximately twofold higher than after radiation alone. There was no apparent
      dependence of the cisplatin-induced changes in SF2 values upon the level of cell
      killing by cisplatin. However, there is a suggestion that concomitant cisplatin
      administration may have a differential effect in inherently radiosensitive and
      resistant human tumor cell lines. CONCLUSIONS: Our data suggest that concomitant
      cisplatin/radiotherapy regimens may result in a higher level of local tumor
      control, but primarily through additive toxicity and not through
      radiosensitization. Future improvements in local tumor control may, thus, be
      derived by increasing the total dose of cisplatin.

PMID- 8567338
TI  - Ethacrynic acid: a novel radiation enhancer in human carcinoma cells.
AB  - PURPOSE: Because agents that interfere with thiol metabolism and glutathione S
      transferase (GST) functions have been shown to enhance antitumor effects of
      alkylating agents in vitro and in vivo, the present study was conceived on the
      basis that an inhibitor of GST would enhance the radiation response of some
      selected human carcinoma cells. Ethacrynic acid (EA) was chosen for the study
      because it is an effective inhibitor of GST and is a well known diuretic in
      humans. METHODS AND MATERIALS: Experiments were carried out with well-established
      human tumor cells in culture growing in Eagle's minimum essential medium (MEM)
      supplemented with 10% fetal calf serum (FCS). Cell lines used were MCF-7, MCF-7
      adriamycin resistant (AR) cells (breast carcinoma), HT-29 cells (colon
      carcinoma), DU-145 cells (prostate carcinoma), and U-373 cells (malignant
      glioma). Cell survival following the exposure of cells to drug alone, radiation
      alone, and a combined treatment was assayed by determining the colony-forming
      ability of single plated cells in culture to obtain dose-survival curves. The
      drug enhancement ratio was correlated with levels of GST. RESULTS: The
      cytotoxicity of EA was most pronounced in MCF-7, U-373, and DU-145 cells compared
      to MCF-7 AR and HT-29 cells. The levels of GST activity were found to be lower in
      those EA-sensitive cells. A significant radiation enhancement was obtained with
      EA-sensitive cells exposed to nontoxic concentrations of the drug immediately
      before or after irradiation. The sensitizer enhancement ratio (SER) of MCF-7
      cells was 1.55 with EA (20 micrograms/ml), while the SER of MCF-7 AR was less
      than 1.1. Based on five different human tumor cells, a clear inverse relationship
      was demonstrated between the magnitude of SER and GST levels of tumor cells prior
      to the combined treatment. CONCLUSION: The present results suggest that EA, which
      acts as both a reversible and irreversible inhibitor of GST activity, could
      significantly enhance the radiation response of human cancer cells and the level
      of GST in tumor cells may predict the magnitude of radiation enhancement with EA.
      Ethacrynic acid would be an excellent drug as a radiosensitizer for further in
      vivo tumor study.

PMID- 8567339
TI  - Timing of concomitant boost irradiation affects incidence and severity of
      intestinal complications.
AB  - PURPOSE: In an effort to increase the therapeutic ratio of radiation therapy, so
      called "nonstandard" irradiation regimens are being used more frequently. One
      such regimen, concomitant boost, entails giving a second daily fraction during
      part of the treatment course, thus reducing the total treatment time and
      decreasing the opportunity for tumor cell proliferation during treatment. The
      probability of tumor control is, therefore, increased for a given total dose.
      Timing of the boost, i.e., whether it is given early or late during the treatment
      course, affects both normal tissue and tumor response. This study assessed the
      influence of timing of a second daily boost on the development of intestinal
      radiation injury in a rat model. METHODS AND MATERIALS: A functionally intact
      segment of distal ileum was sutured to the inside of the scrotum in 52
      orchiectomized, male Sprague-Dawley rats. After a 3-week postoperative recovery
      period, the intestine contained in the "scrotal hernia" was irradiated. All rats
      received a total dose of 50.4 Gy, given over a 12-day period as two different
      boost regimens, daily fractions of 2.8 Gy plus six concomitant boost doses of 2.8
      Gy. The early boost group received the additional boost during the first 6 days
      and the late boost group received the additional boost during the last 6 days.
      The boost was given 6 h after the daily fraction. Groups of rats were sacrificed
      at 24 h (acute changes), 2 weeks (subacute changes), and 26 weeks (chronic
      changes) after the end of the irradiation schedule. Radiation injury was assessed
      by frequency of radiation-induced complications, histopathologic radiation injury
      score, collagen content, and epithelial cytokinetics. RESULTS: Radiation injury
      in the early boost group was significantly more severe than in the late boost
      group in terms of incidence of complication and histopathologic injury. Relative
      collagen content of irradiated intestine was significantly increased in the early
      boost group when compared to the late boost group at 2 weeks and at 26 weeks.
      Irradiated intestine in the early boost group exhibited decreased labeling index
      at 2 weeks, whereas irradiated intestine in the late boost group exhibited normal
      labeling index and increased total crypt cellularity at 2 weeks. CONCLUSION: When
      small intestine has to be included in the treatment field during radiation
      therapy, concomitant boost should be given towards the end of the radiation
      schedule, after the onset of compensatory proliferation, to minimized the risk of
      subsequent complications.

PMID- 8567340
TI  - Impact of biological clearance on tumor radioresponsiveness.
AB  - PURPOSE: To determine the capacity of biological clearance in tumor regression
      following radiotherapy by using metastatic brain tumors as a clinical model in
      which mechanical clearance is negligible. METHODS AND MATERIALS: Thirty-eight
      tumors (19 nonsmall cell lung cancer, 11 small cell lung cancer, and 8 nonlung
      cancer) in 23 patients were followed with computed tomography (CT) scans over 3
      months or more following initiation of radiotherapy, with doses ranging between
      34 and 66 Gy. The tumor regression rate (RR; mm3/day), which represented the
      capacity of biological clearance, was calculated for each CT observation period.
      The complete response (CR) rate was calculated. The relationship between RR and
      tumor diameter was determined with regression analysis in conjunction with the
      pattern of contrast enhancement and the type of primary disease. The change of
      the RR also was examined. RESULTS: The CR rate was 60.5% for the total group; it
      was lower for ring-enhanced tumors (41.7%) than diffusely enhanced tumors
      (69.2%), which included mostly small cell lung cancer metastases. The RR
      correlated significantly with the tumor diameter (D), with a regression curve of
      exponential function (RR = 0.035 *D2.5). The RR varied widely and was rather
      large until 40 days following initiation of radiotherapy, especially for the
      subgroups of diffusely enhanced tumors and the small cell lung cancer tumors, and
      became rather constant thereafter. CONCLUSION: A tumor diameter exponent in the
      regression curve of smaller than 3.0 indicates that the larger the tumor volume
      is, the smaller the capacity of biological clearance. The capacity of biological
      clearance also is dependent on vascularity and cellularity of the tumor
      components expressed by the pattern of contrast enhancement.

PMID- 8567341
TI  - On the relation between size of necrosis and diameter of tumor spheroids.
AB  - PURPOSE: In many previous experimental studies on multicellular tumor spheroids,
      the spheroid diameter at which central necrosis develops has been determined to
      be twice the thickness of the viable cell rim measured at a later stage of
      spheroid growth. This procedure tacitly assumes that there is a linear relation
      between the diameter of necrosis and that of the whole spheroid over the entire
      range of emergence and growth of necrosis. However, some experimental
      investigations have demonstrated that necroses do not grow gradually with
      spheroid diameter, but show a rapid initial increase, once a few cells have died.
      The present article offers an explanation for this phenomenon, which is derived
      from basic diffusion theory. METHODS AND MATERIALS: A theoretical relation
      between sizes of spheroids and of their central necroses is developed, which is
      based on the assumption that formation of necrosis is caused by depletion of
      substrates or accumulation of metabolic waste products. In a second part, the
      theoretical model is fitted to experimental data from the literature, and oxygen
      consumption rate as a function of spheroid size is determined. RESULTS: It turns
      out that the model closely mimics the experimentally observed behavior described
      above. These experimental results, therefore, do not furnish any evidence for
      assuming other hypotheses of necrosis formation. Resulting O2 consumption rates
      are well in the range of previously published data. In all cases, approximations
      to the measured data are better than the corresponding linear squares fits.
      CONCLUSION: At least in some tumor cell lines, depletion of substrates or
      accumulation of waste products can explain formation of necrosis without the
      assumption of any additional mechanisms. Moreover, the model presented in this
      article offers an alternative way of determining the turnover rate of a substrate
      or metabolic waste product provided that depletion/accumulation of this substance
      represents the cause for necrosis development.

PMID- 8567342
TI  - Response of the microtubular cytoskeleton following hyperthermia as a prognostic
      indicator of survival of Chinese hamster ovary cells.
AB  - PURPOSE: The response of the microtubular (MT) cytoskeleton to hyperthermia was
      assessed as a prognostic indicator of cytotoxicity. METHODS AND MATERIALS: Heat
      induced collapse and subsequent recovery of the MT system were compared with
      survival for both nonthermotolerant (NT) and thermotolerant (TT) G1 populations
      of Chinese hamster ovary (CHO) cells. The response of the MT system was monitored
      using immunofluorescence staining. The G1 populations of NT and TT cells were
      heated by submersion in 45.0 and 43.0 degrees C waterbaths. RESULTS: Heat-induced
      perinuclear collapse of the MT system did not correlate with survival for the NT
      and TT populations. However, recovery of the organization of the MT cytoskeleton
      was correlatable with survival. The regression line of survival plotted as a
      function of MT recovery is fit by: y = -0.43 + 1.03x, r2 = 0.95 (p < 0.0005).
      CONCLUSION: Restoration of the organization of the MT cytoskeleton following
      hyperthermia may be used as a prognostic indicator of survival of CHO cells
      heated in G1.

PMID- 8567343
TI  - A multirod collimator for neutron therapy.
AB  - PURPOSE: To design, construct, and commission a multirod collimator for producing
      irregularly shaped fields in neutron radiation therapy. To demonstrate the
      reliability and applicability of this device to routine use with a
      superconducting cyclotron for neutron therapy. METHODS AND MATERIALS: A multirod
      collimator has been designed, constructed, and thoroughly tested to investigate
      its radiological properties; neutron transmission characteristics, beam profiles,
      and penumbral widths as a function of field size and depth in a phantom, and the
      spatial resolution of the rod array, have been measured. A wide variety of
      irregularly shaped fields, used routinely in neutron radiation therapy, have been
      produced, including fields that incorporate partial transmission blocks. The
      performance of the collimator has been closely monitored over a period of 20
      months to accurately assess reliability. RESULTS: The multirod collimator has
      been in routine use for 32 months, and during this time a total of 7025 neutron
      fields has been treated. For the latter 20 months of this period, detailed
      performance records show that collimator failure has caused 28.4 h of downtime
      during the patient treatment day. Only 5.25 h of this downtime was experienced in
      the last 12 months (0.22% of the available treatment time). The results of
      collimator attenuation and beam profile measurements show that the radiological
      properties of the collimator are comparable to those of other collimator systems
      used for neutron radiation therapy. Isodose measurements in a water phantom show
      that the spatial resolution of the rods is superior to that of the leaves used in
      neutron multileaf collimators. The ability of the multirod collimator to produce
      many irregularly shaped fields commonly encountered in neutron radiation therapy
      has been demonstrated. Shaped fields for prostate, head and neck, soft tissue
      sarcomas, lung, thyroid, rectum, bladder, colon, breast, pancreas, and
      gynecological tumors have been produced. For some prostate cases, the device has
      been used to produce partial transmission blocks. CONCLUSIONS: A novel multirod
      collimator has been designed, constructed, and successfully applied in the
      routine treatment of neutron radiation therapy patients.

PMID- 8567344
TI  - Quantitative assessment of radiation-induced lung changes by computerized optical
      densitometry of routine chest x-rays.
AB  - PURPOSE: To develop a quantitative assay of radiological lung changes after
      postmastectomy radiotherapy applicable for analysis of routine chest x-rays.
      METHODS AND MATERIALS: The assay relies on measurement of the optical density of
      chest x-rays by means of a standard personal computer-controlled film
      densitometer used for scanning dosimetry films. Density profiles were recorded at
      1 mm steps along two reference lines in each lung. The crossing between the
      clavicula and the first rib in the x-ray projection was used as an easily
      identifiable anatomical landmark and was used to establish two parallel cranio
      caudal reference lines separated by 20 mm. The starting point for recording
      optical densities was 5 mm below a line perpendicular to the reference lines and
      tangent to the top of the lung. Data were stored in a computer file for
      subsequent processing. The optical film densities in the apex of the lungs were
      converted into equivalent absorber thickness (EAT). To minimize the dependency on
      technical factors, the unirradiated lung was used as a control. Lung density
      changes were quantified by the relative change in EAT (REAT), which was evaluated
      as the difference between the summed EATs along the reference lines in the two
      lungs, corrected for any pretreatment difference in lung density, and taken as a
      percentage of the pretreatment EAT value of the lung. RESULTS: Four different
      test were carried out to investigate the reproducibility and validity of the
      proposed assay. (a) An anthropomorphic phantom was used to test the relationship
      between REAT and the layer of plastic absorber placed in front of one lung. A
      linear relationship was found with a correlation coefficient of 0.9993. (b) A
      series of 10 repeat measurements of the same arbitrarily chosen x-ray showed a
      mean REAT value of 9.8%, with a standard deviation of 0.21%. (c) Forty-three
      chest x-rays exposed on the same day were available from the clinical series.
      These were treated as double determinations of REAT values, and the standard
      deviation was estimated at 1.35%. (d) REAT values estimated with this assay were
      significantly correlated with the scores of two experienced specialists, an
      oncologist and a radiologist (Spearman's rank correlation coefficient being
      0.605, p < 10(-8)). CONCLUSION: This assay quantifies radiation-induced lung
      injury from routine chest x-rays. Thus, it is possible to take advantage of the
      very large retrospective materials available in most oncological institutions.
      The assay has been validated in a phantom experiment and shown to be
      reproducible. Furthermore, it is technically easy to perform.

PMID- 8567345
TI  - Preoperative concomitant radiochemotherapy in squamous cell carcinoma of the
      esophagus: results of a study of 56 patients.
AB  - PURPOSE: Today the prognosis for patients with esophageal carcinoma still remains
      quite poor. In the last few years interesting results have been obtained by
      associating radio- and chemotherapy with or without surgery with this type of
      cancer. In this work we report the results of concomitant radio- and chemotherapy
      in a split-course schedule preceeding surgery for the treatment of squamous cell
      carcinomas of the esophagus. METHODS AND MATERIALS: Fifty-six patients with
      squamous cell carcinomas of the esophagus were treated between April 1989 and
      September 1993 in the Centre Hospitalier Universitaire in Brest, France with two
      courses of preoperative concomitant radiochemotherapy, separated by a 2-week
      interval, and followed by surgery (each course 18.5 Gy in five fractions, days 1
      5 with continuous infusion 5-fluorouracil (5-FU) 800 mg/m2 days 1-5 and
      cisplatinum 70 mg/m2 day 2). Patients who had responded well to preoperative
      treatment (response > 50%) received four more courses of chemotherapy alone. The
      two patients who were not operated and those with palliative surgery received a
      third course of radiochemotherapy (radiotherapy 12 Gy in five fractions, days 1
      5). RESULTS: Fifty-four patients were operated on. Twenty-one showed histological
      complete response at surgery (37.5% of the whole group). Actuarial survival for
      the 56 patients was 55% at 3 years and 30% at 4 years, with a median survival of
      37.4 months (40.4 months for complete responders to preoperative treatment).
      Toxicity of preoperative concomitant radio-chemotherapy was low (5-FU had to be
      stopped in one patient because of cardiac rythm disturbances and in another
      patient because of aplasia Grade 4 associated with infection after the first
      course). Postoperative mortality was 11% (six patients). CONCLUSION: This
      combination of preoperative radiochemotherapy followed by surgery seems to
      improve both response rates and survival in patients with esophageal cancer when
      compared with previous patients treated with surgery alone in our hospital or
      with results found in literature and it warrants further studies.

PMID- 8567346
TI  - A prospective analysis of subacute thyroid dysfunction after neck irradiation.
AB  - PURPOSE: Exposure of the thyroid to therapeutic doses of external irradiation has
      been demonstrated to induce thyroid dysfunction. This study was designed to
      assess the relationship between irradiation and early thyroid dysfunction,
      prospectively. METHODS AND MATERIALS: Twenty patients in whom the thyroid was
      incidentally exposed to therapeutic doses of irradiation were studied. The dose
      given to the thyroid was 40-54 Gy over 4-7 weeks. Thyroid function tests,
      including serum thyroid stimulating hormone (TSH), free thyroxine (free T4), free
      triiodothyronine (free T3), antithyroglobulin antibody, and antimicrosomal
      antibody, were performed prior to irradiation and at 3, 6, and 12 months after
      radiotherapy. RESULTS: Serum TSH levels did not change significantly at 3 months
      after irradiation (mean TSH level: 1.33 microU/ml before irradiation, 1.74
      microU/ml at 3 months, p = 0.11). However, a significant elevation was noted at 6
      months (mean TSH: 3.50 microU/ml at 6 months, p = 0.0001, vs. preirradiation),
      when TSH levels were higher than preirradiation levels in 19 of 20 patients.
      After irradiation, 13 patients remained in a euthyroid state (euthyroid group),
      while in the other 7 patients hypothyroidism occurred (hypothyroid group) and
      thyroid hormone-replacement therapy was performed. After 6 months, elevation of
      TSH was less significant in the euthyroid group, whereas elevation of TSH
      persisted continuously and exponentially in the hypothyroid group. Thyroid
      autoantibodies did not turn positive in any patient during follow-up.
      CONCLUSIONS: Damage of the thyroid develops in most patients when the organ is
      exposed to radiation. This radiation-induced damage is initially manifested
      within 6 months after irradiation.

PMID- 8567347
TI  - A phase I study of combined radiation therapy with 5-fluorouracil and low dose
      folinic acid in patients with locally advanced pancreatic or biliary carcinoma.
AB  - PURPOSE: To evaluate the toxicities of a Phase I study of radiation therapy with
      concurrent 5-fluorouracil (5FU) and low dose folinic acid in patients with
      locally advanced pancreatic or biliary carcinoma. METHODS AND MATERIALS: Twenty
      seven patients with locally advanced carcinoma of the pancreas (n = 19), bile
      duct (n = 7), and gall bladder (n = 1) were entered into a Phase I study of
      combined radiation therapy, 5FU, and folinic acid. Radiation was given as a split
      course of 40 Gy in 20 daily fractions with a gap of 2 weeks after 20 Gy. 5
      Fluorouracil, 300 to 375 mg/m2/day and folinic acid, 20 mg/m2/day were given as
      an i.v. bolus daily for 5 days beginning on day 1 and again on day 29. RESULTS:
      Eight patients developed Grade 3 or 4 toxicities (National Cancer Institute
      common toxicity criteria) including nausea and vomiting (n = 4), oral mucositis
      (n = 4), myelosuppression (n = 2), infection (n = 2), and diarrhea (n = 1). Four
      patients did not complete the planned protocol due to treatment toxicities. There
      were two treatment deaths secondary to septic neutropenia. Treatment toxicity
      appeared to be related to age (> 70), performance status (ECOG = 2), and 5FU dose
      (> 350 mg/m2/day). CONCLUSION: This protocol is poorly tolerated by elderly
      patients or those with poor performance status, and 350 mg/m2/day is our
      recommended dose for 5FU as given in this protocol.

PMID- 8567348
TI  - Analysis of prostate and seminal vesicle motion: implications for treatment
      planning.
AB  - PURPOSE: To quantify prostate and seminal vesicle positional changes (target
      motion) between treatment planning and delivery, and to identify the factors
      contributing to target motion. METHODS AND MATERIALS: Thirty patients with
      adenocarcinoma of the prostate were prospectively evaluated by analyzing two
      sequential planning computerized tomography (CT) scans (S1, obtained prior to
      treatment, and S2, obtained during the fourth week of treatment) for each
      patient. All anatomical volumes of interest (soft tissue and bony) were
      reconstructed from transverse CT images and projected onto anterior and lateral
      beam's-eye view projections. Positional changes between S1 and S2 were eliminated
      by applying a rigid body translation and rotation. Target motion was then
      measured by recording the positional change between S1 and S2 at the edges
      (right, left, superior, inferior). Potential correlation of target motion with
      bladder volume, rectal volume, and rectal diameter changes were evaluated by
      linear regression analysis. RESULTS: Neither the prostate nor seminal vesicles
      remained fixed with respect to bony anatomy between S1 and S2. The distribution
      of positional changes were generally small (< 0.5 cm), but maximum displacements
      of 1.5-2.2 cm did occur, particularly in the lateral view. In this study, bladder
      volume changes between the scans were small and did not correlate with target
      motion (P = 0.67). Both rectal volume and rectal diameter changes correlated with
      target motion for both the prostate (p = 0.004 and 0.005, respectively) and
      seminal vesicles (p < 0.001 and < 0.001, respectively). However, neither the
      initial rectal volume nor the initial rectal diameter could be used to predict
      subsequent target motion when evaluated either singly or as part of a multiple
      regression model. CONCLUSIONS: Target motion occurs during the course of
      treatment planning and delivery and should be considered when designing conformal
      radiation fields. Although the target position at the time of planning CT may
      differ substantially from the mean treatment position, target motion cannot be
      predicted by evaluating simply measured parameters from a single scan, or double
      scan sequence.

PMID- 8567349
TI  - Activation of lavage lymphocytes in lung injuries caused by radiotherapy for lung
      cancer.
AB  - PURPOSE: Radiation pneumonitis sometimes extends beyond the irradiated area of a
      lung and can also affect the opposite lung. Some immunological mechanisms, in
      addition to simple direct injury of the lungs by radiation, seem to be involved
      in the onset of radiation pneumonitis. To clarify such mechanisms, the effects of
      radiation on local inflammatory cells in lungs, in particular, lymphocytes, were
      examined. METHODS AND MATERIALS: A comparison was made of bronchoalveolar lavage
      fluid (BALF) findings from 13 irradiated patients (RT group) and 15 nonirradiated
      patients (non-RT group) with lung cancer. Patients who later developed radiation
      pneumonitis (RP group) and those who did not (RP-free group) were also compared.
      Using a two-color flowcytometer, radiation-induced changes in local inflammatory
      cells in lungs were analyzed. This included analyses of human leukocyte
      associated antigen (HLADR) and intercellular adhesion molecule-1 (ICAM-1)
      expression on T-cells, which are though to be involved in cell activation and
      interactions between cells. RESULTS: The following aspects of BALF were higher in
      the RT group than in the non-RT group: (a) the percentage of lymphocytes and
      eosinophiles; (b) the incidence of HLADR-positive CD4+T-cells and HLADR-positive
      CD8+T-cells; and (c) the incidence of ICAM-1--positive T-cells. The following
      aspects of BALF were higher in the RP group than in the RP-free group: (a) the
      total cell counts; (b) the percentage of lymphocytes; and (c) the incidence of
      ICAM-1-positive T-cells. A significant relationship was seen between the
      incidence of ICAM-1 expression on T-cells and the number of days from the
      initiation of radiotherapy to the onset of radiation pneumonitis. CONCLUSION:
      These data suggest that irradiation can induce accumulation of activated T-cells
      (HLADR and ICAM-1--positive T-cells) in the lung. This accumulation may be
      closely linked to radiation-induced lung injury. It is also suggested that the
      incidence of ICAM-1--positive T-cells in BALF may serve as a useful clinical
      marker of radiation pneumonitis.

PMID- 8567350
TI  - Evaluation of an objective plan-evaluation model in the three dimensional
      treatment of nonsmall cell lung cancer.
AB  - PURPOSE: Evaluation of three dimensional (3D) radiotherapy plans is difficult
      because it requires the review of vast amounts of data. Selecting the optimal
      plan from a set of competing plans involves making trade-offs among the doses
      delivered to the target volumes and normal tissues. The purpose of this study was
      to test an objective plan-evaluation model and evaluate its clinical usefulness
      in 3D treatment planning for nonsmall cell lung cancer. METHODS AND MATERIALS:
      Twenty patients with inoperable nonsmall cell lung cancer treated with definitive
      radiotherapy were studied using full 3D techniques for treatment design and
      implementation. For each patient, the evaluator (the treating radiation
      oncologist) initially ranked three plans using room-view dose-surface displays
      and dose-volume histograms, and identified the issues that needed to be improved.
      The three plans were then ranked by the objective plan-evaluation model. A figure
      of merit (FOM) was computed for each plan by combining the numerical score
      (utility in decision-theoretic terms) for each clinical issue. The utility was
      computed from a probability of occurrence of the issue and a physician-specific
      weight indicating its clinical relevance. The FOM was used to rank the competing
      plans for a patient, and the utility was used to identify issues that needed to
      be improved. These were compared with the initial evaluations of the physician
      and discrepancies were analyzed. The issues identified in the best treatment plan
      were then used to attempt further manual optimization of this plan. RESULTS: For
      the 20 patients (60 plans) in the study, the final plan ranking produced by the
      plan-evaluation model had an initial 73% agreement with the ranking provided by
      the evaluator. After discrepant cases were reviewed by the physician, the model
      was usually judged more objective or "correct." In most cases the model was also
      able to correctly identify the issues that needed improvement in each plan.
      Subsequent replanning confirmed that further manual plan optimization could be
      achieved in 17 patients. CONCLUSION: The objective plan-evaluation model was able
      to rank lung cancer radiotherapy plans from best to worst. It was useful in
      improving plans and may be useful to physicians in defining goals for patients
      based on the ability to effectively and safely treat their tumors.

PMID- 8567352
TI  - Dosimetric considerations in radiation therapy of coin lesions of the lung.
AB  - PURPOSE: The dose distribution in small lung lesions (coin lesions) is determined
      by the combined effects of reduced attenuation and electronic disequilibrium. The
      magnitude of the dose delivered also depends on the algorithm used to correct for
      reduced lung density. These effects are investigated experimentally and
      computationally for 10 MV photons. METHODS AND MATERIALS: Using a polystyrene
      miniphantom embedded in cork or cedar, thermoluminescent dosimetry and film
      dosimetry was performed to investigate interface effects and the central dose per
      monitor unit (MU). Three frequently applied calculation techniques--no density
      correction, ratio of tissue maximum ratios (TMRs), and the Batho correction--were
      also used to calculate the dose per MU. The measurements and calculations were
      compared with a one-dimensional phenomenological theory with parameters taken
      from the literature. RESULTS: The measurements at the entrance surface and center
      of the miniphantom agreed well with the predictions of the phenomenological
      theory. The interface regions are usually thin enough (2-3 mm) to be clinically
      unimportant for 10 MV. Depending on the algorithm used to correct for decreased
      lung density, the lesion dose may be larger or smaller than the prescribed dose
      by as much as 20% in extreme cases. A clinical example is presented. CONCLUSIONS:
      In comparing clinical results of treatments of small lung lesions, it is
      important to be aware of the density correction used.

PMID- 8567351
TI  - Radiation dose perturbation at tissue-titanium dental interfaces in head and neck
      cancer patients.
AB  - PURPOSE: To determine the dose perturbation effects at the tissue-metal implant
      interfaces in head and neck cancer patients treated with 6 MV and 10 MV photon
      beams. METHODS AND MATERIALS: Phantom measurements were performed to investigate
      the magnitude of dose perturbation to the tissue adjacent to the titanium alloy
      implants with (100 mu and 500 mu thick) and without hydroxylapatite (HA) coating.
      Radiographic and radiochromic films were placed at the upper (and lower) surface
      of circular metal discs (diameter x thickness: 15 x 3.2, 48 x 3.2, 48 x 3.8 mm2)
      in a solid water phantom and were exposed perpendicular to radiation beams. The
      dosimeters were scanned with automatic film scanners. Using a thin-window
      parallel-plate ion chamber, dose perturbation were measured for a 48 x 3.2 mm2
      disc. RESULTS: At the upper surface of the tissue-dental implant interface, the
      radiographic data indicate that for 15 x 3.2 mm2 uncoated, as well as 100 mu
      coated discs, dose perturbation is about +22.5% and +20.0% using 6 MV and 10 MV
      photon beams, respectively. For 48 x 3.2 mm2 discs, these values basically remain
      the same. However, for 48 x 3.8 mm2 discs, these values increase slightly to
      about +23.0% and +20.5% for 6 MV and 10 MV beams, respectively. For 48 x 3.2 mm2
      discs with 500 mu coating, dose enhancement is slightly lower than that obtained
      for uncoated and 100 mu coated discs for each beam energy studied. At the lower
      interface for 15 x 3.2 mm2 and 48 x 3.2 mm2 uncoated and 100 mu coated discs,
      dose reduction is similar and is about -13.5% and -9.5% for 6 MV and 10 MV beams,
      respectively. For 48 x 3.8 mm2 discs, dose reduction is about -14.5% and -10.0%
      for 6 MV and 10 MV beams, respectively. For 48 x 3.2 mm2 discs with 500 mu
      coating, the dose reduction were slightly higher than those for uncoated and 100
      mu coated discs. CONCLUSIONS: For the beam energies studied, dose enhancement is
      slightly larger for the lower energy beam. The results of dose perturbation were
      similar for 100 mu coated and uncoated discs. These results were slightly lower
      for the 500 mu coated discs but are not clinically significant. The dosimetry
      results obtained from radiochromic films were similar to the ones obtained from
      radiographic film. The dose enhancement results obtained from ion chamber
      dosimetry are higher than those obtained from film dosimetry. The ion chamber
      data represent the data at "true" tissue-titanium interface, whereas the ones
      obtained from film dosimetry represent the data at film-titanium interface.

PMID- 8567353
TI  - Quantitative vs. subjective portal verification using digital portal images.
AB  - PURPOSE: Off-line, computer-aided prescription (simulator) and treatment (portal)
      image registration using chamfer matching has been implemented on PC based
      viewing station. The purposes of this study were (a) to evaluate the performance
      of interactive anatomy and field edge extraction and subsequent registration, and
      (b) to compare observer's perceptions of field accuracy with measured
      discrepancies following anatomical registration. METHODS AND MATERIALS:
      Prescription-treatment image pairs for 48 different patients were examined in
      this study. Digital prescription images were produced with the aid of a
      television camera and a digital frame grabber, while the treatment images were
      obtained directly from an on-line portal imaging system. To facilitate perception
      of low contrast anatomical detail, on-line portal images were enhanced with
      selective adaptive histogram equalization prior to extraction of anatomical
      edges. Following interactive extraction of anatomical and field border
      information by an experienced observer, the identified anatomy was registered
      using chamfer matching. The degree of conformity between the prescription and
      treatment fields was quantified using several parameters, which included relative
      prescription field coverage and overcoverage, as well as the translational and
      rotational displacements as measured by chamfer matching applied to the
      boundaries of the two fields. These quantitative measures were compared with
      subjective evaluations made by four radiation oncologists. RESULTS: All the
      images in this series that included a range of the most commonly seen treatment
      sites were registered and the conformity parameters were found. The mean
      treatment/prescription field coverage and overcoverage were approximately 95 and
      7%, respectively before registration. The mean translational displacement in the
      transverse and cranio-caudal directions were 2.9 and 3.4 mm, respectively. The
      mean rotational displacement was approximately 2 degrees. For all four
      oncologists, the portals classified as unacceptable, in terms of the field
      placement, exhibited significantly higher (p < 0.03) translational errors in the
      transverse direction. The field coverages were significantly lower (p < 0.05) and
      the translational errors in the cranio-caudal direction were significantly higher
      (p < 0.05) for the portals rated as unacceptable by two of the oncologists.
      CONCLUSIONS: From the parameters that were used to quantify the degree of
      conformity between the prescription and treatment fields, the translational error
      in the transverse direction correlated best with the oncologists' assessments on
      the field placement. Field coverage and translational error in the cranio-caudal
      direction correlated well with assessments of only two out of the four
      participating oncologists. This can be explained by the fact that for the
      majority of treatment sites included in the study the positioning of field
      borders was more critical for the transverse direction. A conclusion for the
      design of future quantitative and automated on-line portal verification systems
      is that they will have to model different perceived significances of different
      types of localization errors intrinsic to oncologist evaluation of portal images.

PMID- 8567354
TI  - Pulsed dose rate and fractionated high dose rate brachytherapy: choice of
      brachytherapy schedules to replace low dose rate treatments.
AB  - PURPOSE: Pulsed dose rate (PDR) brachytherapy is a new type of afterloading
      brachytherapy (BT) in which a continuous low dose rate (LDR) treatment is
      simulated by a series of "pulses," i.e., fractions of short duration (less than
      0.5 h) with intervals between fractions of 1 to a few hours. At the Dr. Daniel
      den Hoed Cancer Center, the term "PDR brachytherapy" is used for treatment
      schedules with a large number of fractions (at least four per day), while the
      term "fractionated high dose rate (HDR) brachytherapy" is used for treatment
      schedules with just one or two brachytherapy fractions per day. Both treatments
      can be applied as alternatives for LDR BT. This article deals with the choice
      between PDR and fractionated HDR schedules and proposes possible fractionation
      schedules. METHODS AND MATERIALS: To calculate HDR and PDR fractionation
      schedules with the intention of being equivalent to LDR BT, the linear-quadratic
      (LQ) model has been used in an incomplete repair formulation as given by Brenner
      and Hall, and by Thames. In contrast to earlier applications of this model, both
      the total physical dose and the overall time were not kept identical for LDR and
      HDR/PDR schedules. A range of possible PDR treatment schedules is presented, both
      for booster applications (in combination with external radiotherapy (ERT) and for
      BT applications as a single treatment. Because the knowledge of both alpha/beta
      values and the half time for repair of sublethal damage (T 1/2), which are
      required for these calculations, is quite limited, calculations regarding the
      equivalence of LDR and PDR treatments have been performed for a wide range of
      values of alpha/beta and T 1/2. The results are presented graphically as PDR/LDR
      dose ratios and as ratios of the PDR/LDR tumor control probabilities. RESULTS: If
      the condition that total physical dose and overall time of a PDR treatment must
      be exactly identical to the values for the corresponding LDR treatment regimen is
      not applied, there appears to be less need for strong fractionation in PDR
      schedules. If the overall time is at least as long as that of the LDR schedule
      and if the total physical dose is (slightly) adapted, PDR schedules can be
      designed using longer pulse intervals of up to 3 h. Schedules with sufficiently
      long intervals have significant logistic advantages in terms of patient care and
      treatment tolerance. However, in general, PDR schedules that apply more
      fractionation have a lower risk of overdosing normal tissues in comparison to
      fractionated HDR schedules. Applying probable ranges for the values of alpha/beta
      and T 1/2, the model calculations indicate that the differences in effects
      between the proposed fractionated HDR and PDR schedules could be rather small. To
      detect the magnitude of these differences, (randomized) clinical studies with
      rather large patient groups might be needed. CONCLUSIONS: Pulsed dose rate
      treatment schedules with longer intervals of up to 3 h appear adequate to replace
      LDR treatment schedules. Whether PDR schedules can, indeed, replace LDR treatment
      schedules and whether they offer detectable advantages over schedules with less
      fractionation (fractionated HDR) should be tested in clinical studies.

PMID- 8567355
TI  - Radiotherapy for carcinoma of the eyelid.

PMID- 8567356
TI  - The search for prognostic genetic indicators of cancer recurrence.

PMID- 8567357
TI  - Pulsed dose rate brachytherapy: can we take advantage of new technology?

PMID- 8567358
TI  - The usefulness of intraoperative radiation therapy in the treatment of pelvic
      recurrence of cervical cancer.

PMID- 8567359
TI  - Intraoperative radiation therapy: cut bait or keep on fishing?

PMID- 8567360
TI  - Major concerns of resident physicians--regarding Ling and Flynn IJROBP 34(1):13
      19; 1996.

PMID- 8567361
TI  - Present status and problems of radiation oncology in Japan.

PMID- 8567362
TI  - Dose-response relationships for late radiation effects in the head and neck:
      regarding the analysis of the RTOG 8313 trial, Fu et al. IJROBP 32:577-588; 1995.

PMID- 8567363
TI  - Welfare of cats depends on humankind.

PMID- 8567364
TI  - Alternative method for retrieving fishhooks from dogs and cats.

PMID- 8567365
TI  - Consider leishmaniasis in differential for monoclonal gammopathies in dogs.

PMID- 8567366
TI  - Dosage consideration for cisapride.

PMID- 8567367
TI  - Article on animal rights/animal liberation still provoking thought.

PMID- 8567368
TI  - Warning about potential for congenital neural larva migrans.

PMID- 8567369
TI  - Clinical investigation of new animal drugs by veterinary practitioners.

PMID- 8567370
TI  - What do food animal practitioners want to read?

PMID- 8567371
TI  - What is your diagnosis? Lateral condylar fracture of the tibial plateau,
      comminuted supracondylar and lateral condylar femoral fractures, fractured public
      bone, and craniodorsal coxofemoral luxation.

PMID- 8567372
TI  - Theriogenology question of the month. Placental insufficiency, probably the
      result of twin fetuses.

PMID- 8567373
TI  - Reflections on the human-animal bond.

PMID- 8567374
TI  - Trends in starting salaries and educational debt of graduates of US veterinary
      medical colleges, 1983 to 1995.

PMID- 8567375
TI  - Benefit-cost analysis of the national pseudorabies virus eradication program.
AB  - An epidemiologic model of pseudorabies virus (PRV) in swine was developed. This
      model was used to project future herd-to-herd disease transmission under
      alternative eradication or control programs over 20 years (1993 to 2012). With
      current PRV eradication program funding, it was projected that prevalence would
      be 23% in higher-risk states in the United States, 10% in moderate-risk states,
      and 1% in lower-risk states. Increased funding for the PRV eradication program
      was projected to reduce PRV prevalence substantially. Productivity and economic
      impacts of PRV also were estimated for the average size farrow-to-finish
      operation. These impacts included mortality for preweaning, nursery,
      growing/finishing, and breeding hogs; market weights and number of market hogs
      sold; farrowing rates, number of live pigs per litter, and number of litters per
      sow-year. Profitability was estimated to be $6/cwt less for PRV-infected herds
      than for uninfected herds. Aggregate effects of PRV eradication programs were
      estimated by use of economic welfare analysis. For all PRV eradication program
      alternatives analyzed, consumers were the major beneficiaries of the program
      because of reduced prices and increased consumption of pork. Estimates of the
      value of economic welfare impacts under the current program with an assumed
      parallel supply-curve shift were determined: consumers gained $336.5 million;
      producers gained $35.9 million; government expenditures were $197.1 million; and
      the benefit/cost ratio of the program was 1.89. Economic welfare measures were
      projected to increase substantially with increased PRV eradication program
      funding. Economic welfare measures also were estimated under other assumptions.

PMID- 8567376
TI  - Compendium of animal rabies control, 1996: National Association of State Public
      Health Veterinarians, Inc.

PMID- 8567377
TI  - Effects of mydriatic agents in cockatoos, African gray parrots, and Blue-fronted
      Amazon parrots.
AB  - OBJECTIVE: To compare, in psittacines, the mydriatic effects of several topically
      applied curariform, sympathomimetic, and parasympatholytic drugs with and without
      the addition of surface-acting penetrating agents. DESIGN: Prospective,
      randomized controlled trial. ANIMALS: 10 adult cockatoos (Cacatua sulphurea
      subspecies), 2 adult African gray parrots (Psittacus erithacus), and 3 adult Blue
      fronted Amazon parrots (Amazona aestiva). PROCEDURE: Three curariform drugs (d
      tubocurarine, pancuronium, and vecuronium bromide) and 2 autonomic drugs
      (atropine and phenylephrine hydrochloride) were evaluated. Drugs were tested with
      and without the addition of a surface-acting penetrating agent, either saponin or
      benzalkonium chloride. The agent that resulted in the most significant change in
      pupillary diameter with the fewest systemic side effects in the cockatoos then
      was evaluated for its effects in the African gray parrots and the Blue-fronted
      Amazon parrots. During each drug trial, 1 eye was randomly selected to receive
      the control drug (0.9% NaCl), and the opposite eye was selected to receive the
      test drug. Each pupil was videotaped 5 (cockatoos only), 15, 30, 45, 60, and 75
      minutes after treatment. Pupil diameters were measured by use of a computerized
      image analysis system. Data for pupil size were analyzed by means of repeated
      measures ANOVA. RESULTS: Vecuronium without the addition of a surface-acting
      penetrating agent produced the most consistent and greatest pupillary dilatation
      in all 3 species with the fewest systemic side effects. CLINICAL IMPLICATIONS:
      Vecuronium is potentially a clinically useful, topical mydriatic agent for use in
      avian species. Documented differences in the prevalence of systemic side effects
      between species suggests that caution should be applied when applying this drug
      bilaterally.

PMID- 8567378
TI  - Bromide toxicosis secondary to renal insufficiency in an epileptic dog.
AB  - Bromide toxicosis was diagnosed in an 8-year-old Labrador Retriever that had been
      treated for epilepsy with potassium bromide, at a dosage of 29 mg/kg of body
      weight/d. Clinical signs included hind limb weakness, ataxia, and disorientation.
      Renal insufficiency, diagnosed by determination of endogenous creatinine
      clearance, was believed to be responsible for the development of bromide
      toxicosis in this dog. Diuresis with physiologic saline solution and
      discontinuation of bromide and phenobarbital treatment resulted in rapid
      resolution of abnormal neurologic signs; however, serum bromide concentrations
      decreased dramatically during diuresis and seizures recurred. Although saline
      diuresis has been recommended for the treatment of bromide intoxication in human
      beings, more conservative measures, such as discontinuation of bromide and short
      term fluid administration, may be more appropriate for epileptic dogs.

PMID- 8567379
TI  - High dietary chloride content associated with loss of therapeutic serum bromide
      concentrations in an epileptic dog.
AB  - Bromide treatment was successful in controlling seizures in an 11-year-old
      Dachshund with epilepsy and presumptive phenobarbital-associated hepatopathy.
      Because bromide does not induce liver enzyme activity and does not seem to be
      hepatotoxic, it can be used to control seizures in dogs with concurrent epilepsy
      and hepatic disease. In this dog, institution of a special calculolytic diet with
      high chloride content was associated with a decrease in serum bromide
      concentrations and the recurrence of seizures. High chloride intake increases the
      elimination of bromide in dogs, leading to higher dosage requirements for bromide
      in dogs fed high-chloride diets.

PMID- 8567380
TI  - Acute lymphoblastic leukemia, hypercalcemia, and pseudohyperkalemia in a dog.
AB  - A 5-month-old sexually intact male Chesapeake Bay Retriever was evaluated for
      lameness of 2 weeks' duration and lymphocytosis. Acute lymphoblastic leukemia was
      diagnosed on the basis of results of cytologic and cytochemical evaluation of a
      bone marrow aspirate. Serum biochemical abnormalities included hypercalcemia and
      hyperkalemia. Hypercalcemia was likely paraneoplastic; hyperkalemia was believed
      to be a result of release of potassium from large numbers of lymphocytes in vitro
      (pseudohyperkalemia). The dog was euthanatized, and necropsy revealed
      infiltration of the hepatic vasculature and sinusoids, renal parenchyma,
      mesenteric and peripheral lymph nodes, bone marrow, and iridial tissue with
      neoplastic cells. Unique features of this case include the young age of the dog
      and the hypercalcemia and hyperkalemia associated with acute lymphoblastic
      anemia.

PMID- 8567381
TI  - Probable recurrent femoral artery thrombosis in a dog with intestinal
      lymphosarcoma.
AB  - An 11-year-old mixed-breed dog was examined because of chronic diarrhea,
      anorexia, and weight loss. Clinicopathologic abnormalities included anemia and
      hypoalbuminemia, and protein-losing enteropathy was identified. Acute,
      unilateral, femoral artery thrombosis developed before the cause of the protein
      losing enteropathy could be identified. The dog was treated with aspirin, and
      sensation and function of the affected limb returned over the next 5 days, but
      thrombosis of the opposite femoral artery then developed. The dog was
      euthanatized, and at necropsy, intestinal lymphosarcoma was the only disease
      process found. Although disseminated intravascular coagulation is a well
      recognized potential complication of neoplasia in dogs, recurrent localized
      thrombosis, as in this dog, also can develop.

PMID- 8567382
TI  - Hepatic abscesses in dogs: 14 cases (1982-1994).
AB  - OBJECTIVES: To determine typical clinical signs and clinicopathologic findings in
      dogs with hepatic abscesses, to assess outcome of treatment, and to evaluate the
      role that abdominal ultrasonography has in the diagnosis of hepatic abscesses in
      dogs and in monitoring response to treatment. DESIGN: Retrospective case series.
      ANIMALS: 14 dogs with hepatic abscesses. RESULTS: Anorexia and lethargy were the
      most common historical complaints, followed by vomiting and diarrhea. Physical
      abnormalities included fever, dehydration, signs of abdominal pain, hepatomegaly,
      and mucosal bleeding. Hematologic abnormalities included leukocytosis with
      neutrophilia, mild to moderate thrombocytopenia, and mild anemia. Serum
      biochemical abnormalities included high alkaline phosphatase and alanine
      aminotransferase activities and high bilirubin concentration; hypoalbuminemia and
      prolonged coagulation values were also reported. Abdominal radiography revealed
      hepatomegaly, poor abdominal detail, a hepatic mass, or splenomegaly in 9 dogs.
      Thoracic radiography revealed alveolar consolidation or mixed
      bronchial/interstitial pulmonary patterns in 6 dogs. Hypoechoic, heteroechoic, or
      hyperechoic masses were identified in all dogs in which ultrasonography was
      performed. Escherichia coli, Clostridium sp, Klebsiella pneumoniae, Enterococcus
      sp, Staphylococcus epidermidis, and S intermedius were the most common bacteria
      isolated from hepatic abscesses. Concurrent infections were identified in the
      biliary tract, spleen, blood, endocardium, lung, prostate gland, peritoneum,
      lymph nodes, salivary gland, or brain of several dogs. Seven dogs died or were
      euthanatized before definitive treatment could be initiated. One dog was
      successfully treated with antibiotics and was alive 12 months after medical
      treatment. Six dogs were treated surgically (ie, full or partial liver lobectomy,
      drainage, abdominal lavage) and medically (ie, antibiotic administration). Five
      of these dogs survived and were alive 12 months after surgery. Ultrasonography
      was used to monitor response to treatment in several dogs. CLINICAL IMPLICATIONS:
      Hepatic abscesses are rare in dogs, but the clinical signs and clinicopathologic
      findings are similar to other inflammatory hepatic disease. Ultrasonography
      revealed abnormalities in all animals in which imaging studies were performed,
      and was successfully used to monitor response to treatment in several dogs.
      Medical and surgical treatments were used successfully to treat hepatic abscesses
      in dogs.

PMID- 8567383
TI  - Chronic obstructive pulmonary disease in horses in Louisiana.
AB  - OBJECTIVE: To evaluate chronic obstructive pulmonary disease of horses in
      Louisiana by assessing the signalment, history, environmental factors, clinical
      signs, and treatment of such horses. DESIGN: Epidemiologic mail survey. SAMPLE
      POPULATION: 83 of 240 veterinarians contacted by mail agreed to take part in the
      survey. Veterinarians contacted were listed as mixed-animal or equine
      practitioners in the 1991/1992 directory of the Louisiana Veterinary Medical
      Association or had submitted a specimen from a horse to the Louisiana Veterinary
      Medical Diagnostic Laboratory within the past 2 years. PROCEDURE: The survey
      contained 47 questions designed to elicit information from owners and
      veterinarians about horses reported to have chronic obstructive pulmonary disease
      (COPD). Questions were included to evaluate age, breed, sex, vaccination history,
      respiratory disease history, environment of primary activity, level of exercise,
      primary residence (pasture or stall), condition of pasture or barn, type and
      condition of feed, clinical signs, concurrent conditions, and treatment regimen
      prescribed. Information from the returned forms was analyzed by using a
      microcomputer program designed for epidemiologic data. RESULTS: Of the 83
      veterinarians who agreed to participate, 31 returned 71 completed questionnaires
      for horses affected with COPD. Most affected horses were mature in age, kept on
      pasture, and had developed clinical signs during the summer months. The most
      consistent clinical signs were dry coughing, slight serous nasal discharge,
      labored expiratory effort, and flaring nostrils. CLINICAL IMPLICATIONS: Summer
      pasture-associated obstructive pulmonary disease appears to be precipitated by
      factors different than those associated with the traditionally diagnosed form of
      COPD and, thus, successful management measures may also vary.

PMID- 8567384
TI  - Evaluation of five common induction protocols by comparison of hemodynamic
      responses to surgical manipulation in halothane-anesthetized horses.
AB  - OBJECTIVE: To determine whether hemodynamic responses of halothane-anesthetized
      horses undergoing surgical procedures depended on anesthetic induction protocols
      used, and to determine whether hemodynamic responses to surgical manipulation
      could be detected. DESIGN: Prospective experimental study without controls.
      ANIMALS: 36 clinically normal horses. PROCEDURE: Horses were allotted to 5 groups
      according to anesthetic induction protocol: acepromazine/guaifenesin/thiamylal,
      acepromazine/guaifenesin/ketamine, xylazine/guaifenesin/thiamylal,
      xylazine/guaifenesin/ketamine, and xylazine/diazepam/ketamine. Anesthesia was
      maintained with halothane. Hemodynamic measurements and blood gas values were
      obtained prior to the start of surgery, during surgery, and after surgery.
      RESULTS: Few differences in hemodynamic measurements existed between horses in
      which anesthesia was induced by 5 anesthetic induction protocols, whether prior
      to the start of surgery or for pooled values for all 3 measurement periods.
      Hemodynamic responses to surgical manipulation were marked and included increased
      mean arterial pressure and systemic vascular resistance, and decreased cardiac
      index and oxygen delivery. CLINICAL IMPLICATIONS: Choice of anesthetic induction
      protocol has little impact on hemodynamic function during surgery in halothane
      anesthetized horses. Surgical stimulation may increase blood pressure, but does
      not improve cardiac index or oxygen delivery.

PMID- 8567385
TI  - Intramuscular administration of ceftiofur sodium versus intramammary infusion of
      penicillin/novobiocin for treatment of Streptococcus agalactiae mastitis in dairy
      cows.
AB  - OBJECTIVE: To determine the efficacy of intramuscular administration of ceftiofur
      sodium as treatment for intramammary infections attributable to Streptococcus
      agalactiae, compared with that for a standard treatment of intramammary infusion
      of penicillin/novobiocin. DESIGN: Prospective, randomized, controlled trial.
      ANIMALS: 72 lactating Holstein cows with intramammary infections caused by S
      agalactiae from 5 commercial dairies in Michigan. PROCEDURE: In 36 of 72 infected
      cows, ceftiofur was administered (2.2 mg/kg of body weight, IM, q 24 h) for 5
      days; 150 mg of novobiocin and 100,000 U of procaine penicillin G was infused
      daily into each mammary gland of the other 36 cows for 2 days. Milk samples were
      collected aseptically at approximately 4 and 8 weeks after initial treatment. If
      cows were determined to be infected at 4 weeks after initial treatment, the
      treatment was repeated. RESULTS: The cure rate at 4 weeks (91.7%) and at 8 weeks
      (96.8%) after initial treatment for the penicillin/novobiocin-treated cows was
      significantly (P < 0.0001) higher, compared with that of the ceftiofur-treated
      cows (2.8 and 9.1%, respectively). Somatic cell counts were significantly (P <
      0.0001) lower in the penicillin/novobiocin-treated group after treatment.
      CLINICAL IMPLICATIONS: Intramuscular administration of ceftiofur is not
      efficacious as a treatment to eliminate intramammary infections caused by S
      agalactiae and should not be used to reduce the prevalence of this organism in
      dairy herds.

PMID- 8567386
TI  - Comparison of two techniques for castration of llamas.
AB  - OBJECTIVE: To compare a prescrotal castration technique with the conventional
      bilateral scrotal incision technique for castration of llamas. DESIGN:
      Prospective randomized controlled trial. ANIMALS: 10 clinically normal, sexually
      intact male llamas. PROCEDURE: Five llamas were castrated by use of a 5-cm skin
      incision located 2 to 3 cm lateral to the ventral midline and approximately 15 cm
      cranial to the scrotum, which was closed with absorbable suture material to allow
      primary healing. Five other llamas were castrated via a more conventional
      technique, with a 5-cm scrotal incision positioned directly over each testis,
      which was allowed to heal by second intention. RESULTS: The prescrotal technique
      required significantly more time to complete; however, no additional anesthesia
      was required to complete the longer procedure. Llamas castrated with the
      prescrotal technique required less aftercare and had less incisional pain when
      the area was palpated. CLINICAL IMPLICATIONS: Both techniques are safe and
      effective. Some clients, however, find the prescrotal technique more
      aesthetically acceptable. The prescrotal technique may be more clinically
      important where fly control is difficult.

PMID- 8567387
TI  - Neosporosis-associated abortion in a dairy goat.
AB  - Neospora canium tachyzoites and tissue cysts were found in tissues of a goat
      fetus aborted after 3.5 months of gestation. The fetus had hydrocephalus and a
      hypoplastic cerebellum. The predominant lesion in the fetus was severe
      encephalitis associated with numerous N canium tissue cysts. Parasites in fetal
      tissues reacted positively with N caninum antibodies in immunohistochemical
      tests. The doe was clinically normal and had a 1:800 antibody titer to N caninum
      as determined by use of an indirect fluorescent antibody test 9 months after
      abortion. Five of 77 other does from this herd also had indirect fluorescent
      antbody titers to N caninum that were > or = 1:100.

PMID- 8567388
TI  - Percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC).

PMID- 8567389
TI  - Infectious retrovirus is inactivated by serum but not by cerebrospinal fluid or
      fluid from tumor bed in patients with malignant glioma.
AB  - Intravenous gene transfer using recombinant retroviruses tends to suffer from a
      low infectious viral titer when conducted in vivo. This is, in part, caused by
      complement-mediated proteolytic inactivation of the retrovirus in human serum.
      However, if the retroviruses were directly injected into the brain, they might
      not be inactivated. Supernatant from amphotropic retrovirus-producing cells
      harboring the BAG vectors was incubated with sera or cerebrospinal fluid (CSF) of
      patients with gliomas or unrelated disorders. The retroviruses were severely
      inactivated in sera. However, no such inactivation was noted in CSF or fluid from
      the tumor bed of glioma patients. These data suggest that gene transfer using
      recombinant retroviruses could be done into the cavity after removal of the tumor
      in glioma patients.

PMID- 8567390
TI  - Effect of hammerhead ribozyme against human thymidylate synthase on the
      cytotoxicity of thymidylate synthase inhibitors.
AB  - One of the resistance mechanisms to folate-based thymidylate synthase (TS)
      inhibitors is the increase in TS activity in tumor cells. Human B lymphoblastoid
      cell line (W1L2) was made resistant to a lipophilic non-polyglutamatable TS
      inhibitor (ZM249148), and the subline (W1L2:R179) showed a 20-fold increase in TS
      enzyme activity with concomitant overexpression of TS mRNA. To overcome the
      resistance, we designed a ribozyme that can cleave the CUC sequences in a triple
      tandemly repeated sequence of TS mRNA. Expression of this ribozyme in W1L2:R179
      cells transfected with Epstein Barr virus-based expression vector resulted in
      sensitization to TS inhibitors concomitantly with a decrease of TS expression.
      The ribozyme expressed in transfectants was shown to be functional in cleaving
      artificial TS RNA in vitro.

PMID- 8567391
TI  - The relation of smoking, alcohol use and obesity to risk of sigmoid colon and
      rectal adenomas.
AB  - We conducted a case-control study, using 429 cases with histologically confirmed
      sigmoid adenoma, 75 cases with rectal adenoma, and 3101 controls showing normal
      colonoscopy at least up to 60 cm from the anus. The subjects were male Self
      Defense Forces personnel aged 48-56 who received a retirement health examination
      including a routine sigmoid- or colonoscopy. Lifestyle characteristics were
      ascertained by a self-administered questionnaire. Smoking in the recent past (<
      or = 10 years preceding the colonoscopy) and smoking in the remote past (> 10
      years before the colonoscopy) were both significantly associated with risk of
      sigmoid adenoma but not with rectal adenoma as a whole. After reciprocal
      adjustment for smoking in the two periods, only smoking in the recent past was
      associated with both sigmoid colon and rectal adenomas. Odds ratios (OR) of
      sigmoid adenoma (and 95% confidence interval) for the categories of 0, 1-150, 151
      250 and > or = 251 cigarette-years were 1.0 (reference), 1.9 (1.3-2.8), 2.1 (1.4
      3.0) and 3.0 (1.9-4.7), respectively (P for trend < 0.01), and those for rectal
      adenoma were 1.0 (reference), 1.2 (0.4 3.2), 3.5 (1.4-8.5) and 2.0 (0.6 6.7),
      respectively (P for trend = 0.03). Alcohol use was significantly positively
      associated with sigmoid adenoma, and insignificantly associated with rectal
      adenoma. Body mass index was significantly positively associated with sigmoid
      adenoma, especially large ones. No such association was found for rectal adenoma.
      These findings suggest that smoking, especially in the recent past, and alcohol
      use are common risk factors for sigmoid colon and rectal adenomas while obesity
      may be exclusively related to the growth of sigmoid adenoma.

PMID- 8567392
TI  - Tea consumption and lung cancer risk: a case-control study in Okinawa, Japan.
AB  - To disclose the relationship between tea consumption and lung cancer risk, we
      analyzed the data from a case-control study conducted in Okinawa, Japan from 1988
      to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence
      matched controls, provided the following major findings. (a) The greater the
      intake of Okinawa tea (a partially fermented tea), the smaller the risk,
      particularly in women. For females, the odds ratios (and 95% confidence
      intervals) for those who consumed 1-4, 5-9, and 10 cups or more of Okinawan tea
      every day, relative to non-daily tea drinkers, were 0.77 (0.28-2.13), 0.77 (0.26
      2.25) and 0.38 (0.12-1.18), respectively (trend: P = 0.032). The corresponding
      odds ratios for males were 0.85 (0.45-1.55), 0.85 (0.45-1.56) and 0.57 (0.31
      1.06) (trend: P = 0.053). (b) The risk reduction by Okinawan tea consumption was
      detected mainly in squamous cell carcinoma. Daily tea consumption significantly
      decreased the risk of squamous cell carcinoma in males and females, the odds
      ratios being 0.50 (95% confidence interval 0.27-0.93) and 0.08 (0.01-0.68),
      respectively. These findings suggest a protective effect of tea consumption
      against lung cancer in humans.

PMID- 8567393
TI  - High positive rate of pS2 expression in forefront intraductal cancerous area in
      breast cancer.
AB  - Multiple sections of 40 consecutive cases with invasive ductal carcinoma of the
      breast, all of which bad wide intraductal cancerous extension, were examined by
      immunohistochemical analysis for evaluation of hormone dependency in several
      areas of breast cancer tissues. In this study, we examined the expression of pS2
      protein in the central invasive area (CIV), central intraductal cancerous area
      (CDC) and forefront intraductal cancerous area (FDC). pS2 staining was positive
      in 52.5% (21/40) of CIV and a significant correlation was found between pS2
      expression in CIV and the estrogen receptor status (ER). pS2 staining was
      positive in 77.5% of CDC and 85.0% of FDC, respectively. A majority (68.4%) of
      the cases that were negative pS2 in CIV were positive for pS2 in FDC. Moreover,
      the cases with noncomedo intraductal carcinoma in premenopausal status showed a
      higher positivity of pS2 expression in FDC than the cases with comedo-carcinoma,
      though the number of cases of comedo-carcinoma was limited. These findings
      suggest that endocrine therapy may be useful after breast conserving treatment
      regardless of the ER status of the primary tumor.

PMID- 8567394
TI  - Quantitative detection of ultraviolet light-induced photoproducts in mouse skin
      by immunohistochemistry.
AB  - UVB-induced cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6
      4)photoproducts [(6-4)photoproducts] in mouse skin DNA were quantitatively
      measured using an immunohistochemical approach with a computer-aided color image
      analyzer. The skins of the C3H/HeN mice were irradiated with ultraviolet B (UV-B,
      280-320 nm), and processed to give conventional formalin-fixed, paraffin-embedded
      histologic sections. Routine immunohistochemistry clearly demonstrated a dose
      dependent induction of both photoproducts. CPDs were detectable at doses > or =
      125 J/m2, while for (6-4)photoproducts, the minimal dose at which they were
      detectable was 250 J/m2 in the present study. A time course study showed that the
      repair of (6-4)photoproducts was more rapid than that of CPDs, and that epidermal
      cells had a higher capacity for their removal than dermal cells. About half of
      the (6-4)photoproducts were excised within the first 24 h after the irradiation,
      and the process was essentially complete by 72 h. In contrast, there was no
      apparent removal (less than 10%) of CPDs in the first 24 h and they only
      completely disappeared from the epidermal cells at 120 h after irradiation. The
      effect of DNA dilution due to increased turnover of epidermal cells after UV-B
      irradiation was evaluated by quantitative immunohistochemical measurement of the
      time course of bromodeoxy-uridine (BrdUrd) incorporated into nuclei at 2 days
      post irradiation when the proliferation reaches a peak. The removal of
      photoproducts was more marked than the decrease in BrdUrd staining. Our results
      suggest that mouse skin cells can repair both (6-4)photoproducts and CPDs, but
      with considerably lower efficiency, especially in the latter case, then human or
      monkey skin cells.

PMID- 8567395
TI  - Prognostic value of p53 protein accumulation in cancer cell nuclei in
      adenocarcinoma of the uterine cervix.
AB  - Adenocarcinoma of the uterine cervix (CxAd) is one of the most distressing
      malignancies of the female reproductive system because of its tendency to spread
      aggressively and to be resistant to radiation and systemic therapies. To clarify
      the prognostic significance of p53 alteration in CxAd, we immunohistochemically
      examined the incidence of p53 nuclear accumulation, which is considered to be
      mostly parallel with p53 gene mutation, and its association with
      clinicopathological parameters in 26 patients with CxAd. The overall incidence of
      p53 nuclear accumulation was 46% (12 of 26), being higher in groups with
      clinically advanced disease, higher degrees of cellular atypia, and deeper
      myometrial invasion, but significantly lower in patients with integration of
      human papillomavirus (HPV) type 16 or 18 DNA. Nuclear p53 immunoreactivity as
      well as lymph node status, depth of invasion and the absence of HPV-DNA
      integration were significant indicators of a poor prognosis. Examination of p53
      nuclear accumulation could be applied to biopsy material, and would be of
      practical assistance in predicting the prognosis of CxAd both preoperatively and
      postoperatively.

PMID- 8567396
TI  - Epithelial-cadherin gene is not mutated in ductal carcinomas of the breast.
AB  - We investigated mutations of the epithelial (E)-cadherin gene and loss of
      heterozygosity (LOH) at flanking loci using three microsatellite markers on the
      long arm of chromosome 16 in 25 ductal carcinomas of the breast. Expression of E
      cadherin was also investigated immunohistochemically. No mutations were detected
      in exons 6 through 9 of the E-cadherin gene. LOH was observed more frequently
      (42%) at D16S402 (16q-ter) than at D16S421 (16q22.3-q23.1) (17%), which is
      located near the E-cadherin gene. Expression of E-cadherin was observed at the
      cell borders in 92% (11/12) of the tumors examined. The absence of mutations in
      the E-cadherin gene and its conserved expression suggest that inactivation of E
      cadherin does not contribute significantly to the invasion or metastatic
      potential of ductal carcinomas of the breast. Furthermore, the high frequency of
      LOH at 16q-ter suggests the existence of another tumor suppressor gene which may
      play a crucial role in the genesis of ductal carcinomas of the breast.

PMID- 8567397
TI  - Expression of sulfomucins in normal mucosae, colorectal adenocarcinomas, and
      metastases.
AB  - We have examined the expression of specific mucin antigens in tissue sections
      from 92 cases of colorectal carcinoma, using sulfomucin-specific monoclonal
      antibody (MAb) 91.9H. The expression of sulfomucins was high in normal mucosae
      and much lower in primary colorectal carcinoma, in metastatic lesions in lymph
      nodes or in liver. The intracellular localization of sulfomucins was also
      different among these tissues. In normal mucosae, MAb 91.9H binding was seen in
      the supranuclear area, presumably Golgi complexes, the luminal surface, and
      secretory products. In primary colorectal carcinomas and in their metastatic
      lesions, MAb 91.9H was preferentially localized in the cell surface and
      substances attached to the luminal surface of glandular structures. Analysis of
      the lysates of normal and tumor tissues showed that very-high-molecular-weight
      components contained the antigenic epitopes. The intensity of MAb 91.9H binding
      was lower in tumors at advanced stages than in tumors at early stages. These high
      molecular-weight components were apparently reactive with MAb FH6 specific for
      sialyl-Le(X) (s-Le(X) structures. Histological specimens with low levels of MAb
      91.9H reactivity often exhibited relatively high levels of MAb FH6 reactivity.
      These two mucins may have reversed expression during carcinogenesis and carcinoma
      progression, and this change may be related to metastatic potential.

PMID- 8567398
TI  - Sex hormone-dependent renal cell carcinogenesis induced by ferric
      nitrilotriacetate in Wistar rats.
AB  - Ferric nitrilotriacetate (Fe-NTA), an iron chelate, induces necrosis of renal
      proximal convoluted tubules as a consequence of lipid peroxidation, and a high
      incidence of renal cell carcinoma (RCC) is also observed in rats and mice. The
      incidence of RCC and the extent of lipid peroxidation are greater in males than
      females. In the present study, the effects of castration or ovariectomy, and sex
      hormone treatment on Fe-NTA-induced renal carcinogenesis in rats were examined.
      Male and female Wistar rats were each divided into 5 groups. In group 1, rats
      were sham-operated and treated intraperitoneally (i.p.) with nitrilotriacetate
      (NTA). In group 2, sham-operated rats were treated with Fe-NTA (5-10 mg
      iron/kg/day, i.p.). Castrated or ovariectomized rats treated with Fe-NTA served
      as group 3. Group 4 or 5 was treated in the same way as group 3, but in addition
      received either testosterone (group 4) or estradiol (group 5). NTA, Fe-NTA or sex
      hormone treatments were initiated 4 weeks after the operation. NTA or Fe-NTA
      treatments were conducted for 12 weeks, and sex hormones were administered for 10
      months. After 10 months of treatment, all rats were autopsied and both kidneys
      were examined histopathologically. In NTA-treated groups, there was no
      pathological change in the kidneys. In Fe-NTA-treated groups (groups 2-5),
      testosterone treatment or ovariectomy increased the incidence of RCC, and
      estradiol treatment or castration decreased the incidence of RCC (male: sham
      operation, castration and testosterone treatment > castration > castration and
      estradiol treatment, female: ovariectomy and testosterone treatment > ovariectomy
      > sham operation, ovariectomy and estradiol treatment). These results indicate
      that sex differences observed in the incidence of RCC induced by Fe-NTA are
      dependent upon sex hormones.

PMID- 8567399
TI  - Intratumoral injection of an adriamycin immunoconjugate against human pancreatic
      cancer xenografts.
AB  - We have evaluated the effect of an adriamycin conjugate of monoclonal antibody
      Nd2 (ADM-Nd2) on the growth rate of SW1990 xenografts grown subcutaneously in
      athymic nude mice. Intravenous or intraperitoneal administration of radiolabeled
      Nd2 resulted in a maximum tumor accumulation of approximately 45% of the initial
      dose/g of tumor 3-7 days after administration. However, administration into the
      tumor produced retention of 1200%ID/g 1 day after, with 50% of this high value
      remaining even at 7 days after administration. In contrast, intratumoral
      administration of a non-specific immunoglobulin showed a lower initial retention
      and rapid loss of label. Both intravenously and intratumorally administered ADM
      Nd2 reduced the growth rate of SW1990 xenografts. While a single intravenous
      administration arrested growth for about two weeks, a single intratumoral
      injection prevented any increase in tumor size even 45 days after administration.
      Xenografts treated with ADM-Nd2 showed degenerative changes at the histological
      level. Neither Nd2 alone nor Adriamycin alone inhibited growth when administered
      at the same dose as the conjugate.

PMID- 8567400
TI  - Inhibition of tumor cell haptotaxis by sodium D-glucaro-delta-lactam (ND2001).
AB  - We used the Boyden chamber system to investigate the mechanism by which the
      antimetastatic agent sodium D-glucaro-delta-lactam (ND2001) inhibits tumor cell
      invasion, and by establishing what ND2001 did not achieve, we were able to
      pinpoint the areas in which it was successful as an inhibitor. ND2001 did not
      inhibit cell adhesion of a highly metastatic B16 melanoma variant (the B16
      variant) to the reconstituted basal membrane Matrigel, nor did it affect the
      production or activity of basal membrane-degrading type i.v. collagenase, but, in
      the Boyden chamber, ND2001 inhibited cell migration of the B16 variant toward a
      chemoattractant, laminin, on the lower surface of a Matrigel-free filter set
      (haptotaxis). Lewis lung carcinoma (3LL) cells that had been treated with ND2001
      also exhibited hardly any haptotaxis, although the cells showed no alteration in
      behavior during cell adhesion to Matrigel. Since ND2001 did succeed in inhibiting
      the pulmonary metastases of the B16 variant and 3LL, we infer that inhibition of
      the metastases by ND2001 in these tumors is likely to be due to the inhibition of
      haptotactic migration.

PMID- 8567401
TI  - Frequent development of murine T-cell lymphomas with TcR alpha/beta+, CD4-/8-
      phenotype after implantation of human inflammatory breast cancer cells in BALB/c
      nude mice.
AB  - Tumors developed quite frequently in some of the visceral organs, including
      spleen and liver, in BALB/c nude mice upon subcutaneously xenografting surgical
      specimens from five different inflammatory breast cancer patients. All of these
      tumors developed within two and a half months to one year after the subcutaneous
      inoculation of surgical specimens. From these tumors, five independent
      transplantable tumors, including tMK-2, tHK-1, tYK-1, tYK-2 and tTY-1 have been
      established. Chromosome analysis, morphologic studies by light and electron
      microscopy and phenotype analysis indicated that these tumors are of mouse
      origin. The tMK-2 tumor was highly metastatic to the spleen and liver when it was
      subcutaneously transplanted into the right scapular region. In addition, the
      region where the tMK-2 tumor cells were subcutaneously inoculated showed an
      apparently inflammatory process represented by erythema. After subcutaneous
      inoculation into the right scapular region, tHK-1, tYK-1, 2, and tTY-1 tumors
      also metastasized to some of the visceral organs, including spleen and liver.
      From these tumors, in vitro cell lines were established. The cells grew in a
      stromal-cell dependent manner under in vitro culture conditions. The cells were
      again tumorigenic at the inoculated region and metastasized to various organs,
      including liver and spleen, of BABL/c nude mice. Histological examination
      revealed that the tumors showed features of malignant lymphoma. Phenotypically,
      these five tumors expressed early T lymphocyte markers as revealed by anti-mouse
      anti-TcR alpha/beta, anti-CD3, CD4 and CD8 monoclonal antibodies. To our
      knowledge, these cell lines are the first T-cell lines showing the phenotype of
      extrathymically differentiated T-cells in the liver.

PMID- 8567402
TI  - Biomodulation by hyperthermia of topoisomerase II-targeting drugs in human
      colorectal cancer cells.
AB  - We examined whether heat stress could enhance the sensitivity of human colon
      cancer WiDr cells to topoisomerase II-targeting anticancer agents, etoposide (VP
      16) and teniposide (VM-26), and also determined the most effective timing for the
      drug administration after exposure to hyperthermia. Both topoisomerase II
      contents and topoisomerase II activity were significantly increased in WiDr cells
      3 to 12 h after heat stress at 43 degrees C for 1 h, in comparison with those
      immediately after the heat stress. Cytotoxicity by VP-16 was most significantly
      enhanced 3 to 12 h after exposure to 43 degrees C for 1 h, but no synergistic
      effect was observed when the drug was administered immediately after the heat
      stress. A combination of VM-26 with heat stress, but not that of a topoisomerase
      I-targeting camptothecin derivative (CPT-11), or vincristine, showed a
      synergistic cytotoxic effect on WiDr cells. VP-16 alone induced cellular
      accumulation at the G2 + M phase, whereas the combination of VP-16 and heat
      stress further increased the cell population at the G2 + M phase, and decreased S
      phase cells. A possible application of the combination of VP-16 and hyperthermia
      in clinical use is discussed.

PMID- 8567403
TI  - Inhibition of 1,2-dimethylhydrazine-induced oxidative DNA damage by green tea
      extract in rat.
AB  - Following subcutaneous injection of 1,2-dimethylhydrazine (DMH), which is
      carcinogenic to rat colon and liver, to Sprague-Dawley rats, a significant
      increase of 8-hydroxydeoxyguanosine (8-OHdG) was observed in the DNA of colonic
      mucosa and liver. The 8-OHdG formation reached the maximal level at about 24 h
      after the DMII injection. On the other hand, no increase of 8-OHdG was observed
      in the DNA of the kidney. Drinking green tea extract (GTE) for ten days prior to
      the DMH injection significantly inhibited the formation of 8-OHdG in the colon.
      These findings demonstrate that DMH causes oxidative damage to the DNA of its
      target organ, and that GTE protects colonic mucosa from this oxidative damage.

PMID- 8567404
TI  - Non-P-glycoprotein-mediated atypical multidrug resistance in a human bladder
      cancer cell line.
AB  - A human bladder cancer cell line resistant to adriamycin (ADM), T24/ADM9 has been
      established in vitro by exposing T24 parent cells to progressively higher
      concentrations of the drug over a period of 12 months. The T24/ADM9 cells were
      found to be 9 times more resistant to ADM than the T24 parent, and showed various
      degrees of cross-resistance to an ADM derivative, vinea alkaloids and a DNA
      topoisomerase II (Topo II)-targeting agent, etoposide. No significant differences
      was observed in the cellular accumulation of ADM between the T24/ADM9 and T24
      parent cells. A Northern blot analysis showed an overexpression of multidrug
      resistance-associated protein (MRP) mRNA, but no overexpression of multidrug
      resistance-1 (MDR1) mRNA was observed in the T24/ADM9 cells. A flow cytometric
      analysis showed that the MDR1 gene product, P-glycoprotein (Pgp), is not
      expressed on the T24/ADM9 cells. T24/ADM9 showed approximately the parental level
      of DNA Topo II catalytic activity. In Western blot and Northern blot analyses,
      however, the cellular level of DNA topo II was apparently much lower in T24/ADM9
      than in the T24 parent. Thus, these results suggest that a decreased cellular
      level of DNA Topo II and an overexpression of MRP gene may be responsible for the
      expression of an MDR phenotype in the T24/ADM9 cells and that such non-Pgp
      mediated, atypical MDR may develop in bladder cancer treated with chemotherapy
      including ADM.

PMID- 8567406
TI  - Binaural response characteristics in isofrequency sheets of the gerbil inferior
      colliculus.
AB  - The spatial distribution of neurons with different binaural response properties
      was studied in two isofrequency areas of the inferior colliculus (IC) of the
      gerbil (Meriones unguiculatus). Single units were recorded in dorsomedial-to
      ventrolaterally oriented electrode penetrations at different rostrocaudal
      positions, within a low (1-2 kHz; N = 108) and a high (23-27 kHz; N = 90) 'iso
      frequency' sheet. Response types were not equally represented within the two
      layers. Within low-frequency regions, 41% of the units were excited following
      sound stimulation of either ear (EE), 21% received an excitatory input from one
      and an inhibitory input from the other ear (EI), and 12% were monaural (E0),
      while within high-frequency regions the distribution was 20% EE, 47% EI and 18%
      E0. However, the spatial arrangement of EE, EI and E0, within the dorsomedial-to
      ventrolateral extent of the isofrequency sheets, was on the whole comparable
      within the two regions: EE-units were accumulated dorsomedially and EI-units
      ventrolaterally in the respective isofrequency sheets. E0-units were distributed
      equally within the low-frequency sheet but occurred more frequently in the middle
      part of the high-frequency lamina. About equal proportions of the units (low
      frequencies 9%; high frequencies 7%) had complex binaural response
      characteristics and were characterized as E/IE. In the rostrocaudal dimension of
      the nucleus, orderly arrangement of different unit types was less obvious. The
      results show that there is a tendency for grouping of different binaural unit
      types within the inferior colliculus. However, these unit types are not strictly
      segregated. Furthermore, it was shown that, despite the differences found in low-
      and high-frequency sites, there is a common scheme of 'binaural representation'
      across frequencies within the IC. Provided that EE-, EI-, and monaural response
      characteristics originate from separate sources, the data point to a convergence
      of binaural brainstem afferents within the IC.

PMID- 8567405
TI  - Diagnosis and treatment of esophageal neoplasms.
AB  - During the last 10 years, the diagnosis and treatment of esophageal carcinoma
      have improved considerably. Endoscopy with Lugol staining and endoscopic
      ultrasonography have been newly introduced and used for early diagnosis and more
      accurate tumor staging. As a result, the number of patients with tumors at an
      early stage has increased remarkably (superficial carcinoma, 23%). In the field
      of treatment, surgical results have improved not only in the short term (30-day
      mortality rate, 4%) but also in the long term (5-year survival rate, 30%). The
      field of operation has been extended (3-field lymph node dissection), with lower
      morbidity and mortality. On the other hand, some techniques for limited treatment
      such as endoscopic mucosal resection, intraluminal radiotherapy, and laser
      irradiation have been introduced for the treatment of esophageal carcinoma at an
      early stage with curative intent. However, there are still many patients with
      esophageal carcinoma at an advanced stage for whom these treatments fail or are
      futile. The role of radiotherapy has been made more significant by the
      introduction of brachytherapy or in combination with other treatment modalities
      such as surgery, chemotherapy and hyperthermia. Response rates for existing
      anticancer drugs used as a single agent are 0-38%. Chemotherapy appears to have
      created significant improvements when used in combined modalities (response rate,
      16-76%). However, chemotherapy for patients with esophageal carcinoma still
      offers an unsatisfactory survival benefit and remains experimental. Studies to
      evaluate multimodality treatments using chemotherapy, combined with radiotherapy
      and/or surgery have started. The contribution of molecular biology to the
      diagnosis and treatment of this disease is a subject for future investigation.

PMID- 8567408
TI  - The effect of contralateral stimulation on cochlear resonance and damping in the
      mustached bat: the role of the medial efferent system.
AB  - In the unanesthetized mustached bat, stimulation of the ear with an acoustic
      transient produces damped oscillations which are evident in the cochlear
      microphonic potential. In this report we demonstrate how the decay time of these
      oscillations is affected by broadband noise presented to the contralateral ear
      (CLN). In the absence of CLN, the mean decay time was 1.94 +/- 0.23 ms, but
      during the presentation of CLN the decay time consistently decreased. The changes
      were finely graded, the higher the CLN, the greater the change. The effect could
      be maintained at a constant level for extended periods of time and this was
      evident when the CLN exceeded 40 dB SPL. The latency of the reflex for 64 dB
      noise was about 11 ms and near maximum changes occurred within 15 ms of CLN
      onset. Sectioning medial efferent nerve fibers in the floor of the fourth
      ventricle or the administration of a single dose of gentamicin eliminated changes
      produced by CLN. The prominence of CM responses to damped oscillations and the
      robust changes in response to CLN make the mustached bat an excellent model for
      studying the influence of the medial efferent system on cochlear mechanics.

PMID- 8567407
TI  - Immunological identification of candidate proteins involved in regulating active
      shape changes of outer hair cells.
AB  - By employing immunological methods, it has been demonstrated that myosin, myosin
      light chain (MLC) and myosin light chain kinase (MLCK) proteins in outer hair
      cells (OHC) are immunologically different from isoforms in platelets, smooth
      muscle and heart muscle, and are probably more related to isoforms found in red
      blood cells (RBC). Moreover, proteins related to band 3 protein (b3p) and protein
      4.1 (p 4.1), ankyrin as well as fodrin and spectrin, but not glycophorin, have
      been identified in isolated OHCs. Both OHCs and RBC differ from other motile non
      muscle cells in their lack of smooth muscle isoforms of actin, their common high
      levels of spectrin-, ankyrin- and band 3-like proteins, as well as the expression
      of the 80 kDa protein 4.1 isoform. The data support the notion that motility of
      OHC may be based upon regulation of the b3p/p 4.1/ankyrin complex, and thus may
      be reminiscent to the active shape changes in RBC.

PMID- 8567409
TI  - Immunocytochemical comparison of posttranslationally modified forms of tubulin in
      the vestibular end-organs of the gerbil: tyrosinated, acetylated and
      polyglutamylated tubulin.
AB  - Specific antibodies against alpha-tubulin, acetylated alpha-tubulin, tyrosinated
      alpha-tubulin and polyglutamylated alpha- and beta-tubulin were used to compare
      the distribution of posttranslationally modified tubulin in the vestibular end
      organs of the gerbil. Antibodies to acetylated tubulin labeled a dense network of
      microtubules in the hair cells and bundles of microtubule in the supporting
      cells. Nerve fibers within and below the epithelium were weakly labeled. This
      localization paralleled that seen with antibodies to alpha-tubulin which labeled
      all microtubules present in the cells. Antibodies to tyrosinated tubulin labeled
      networks and bundles of microtubules in both hair cells and supporting cells and
      in addition gave intense, diffuse labeling in the cytoplasm of both cell types.
      It also labeled the nerve fibers. Antibodies to polyglutamylated tubulin were
      localized mainly in nerve fibers, and in the calyces the labeled microtubules
      were found running circumferentially around the type I sensory hair cells. Thus,
      tyrosinated tubulin was found in the fine networks of microtubules in both the
      sensory and supporting cells. Acetylated tubulin was found in the dense networks
      and bundles of microtubules in the sensory and supporting cells, but did not
      colocalize with polyglutamylated tubulin, which was found predominantly in the
      nerve fibers. The labeling patterns for the tyrosinated tubulin and
      posttranslationally modified tubulins in the sensory and supporting cells of the
      vestibular end organs differ from that seen in the organ of Corti and may reflect
      differences in the stability of the microtubules and the mechanical properties of
      the sensory epithelium.

PMID- 8567410
TI  - A cochlear model using feed-forward outer-hair-cell forces.
AB  - A linear (frequency-domain) model of the cat cochlea (implemented in both 1- and
      2-dimensional versions) has been developed which uses outer hair cell (OHC)
      forces in a geometry which includes the longitudinal (base-to-apex) tilt of the
      outer hair cells (OHCs). When positive (contractile) real OHC force-constants are
      used, very large (50 + dB) response peaks along with very rapidly accumulating
      phase lags (which can reach -50 pi radians) are obtained. The wider the
      longitudinal segmentation, the broader the peaks and the less the phase
      accumulation; 71-microns segmentation produced the most realistic responses.
      These large response peaks are achieved by a small zone of negative resistance
      (ca. 1 mm) just basal to the response peak and the virtual 'zeroing' of the
      basilar membrane's effective impedance over the entire peak region (ca. 2.5 mm).
      To produce these peaks, the OHCs generate about 25-times the incoming acoustic
      power. Inclusion of low-pass filtering in the model's OHC representation
      produces, by contrast, very unrealistic notch-and-peak displacement complexes
      accompanied by very large phase lags, for all segmentation widths used. However,
      when phase reversals of OHC forces are also added, achieved by imbedding a
      resonant system within the tectorial membrane, very realistic peaks and phase
      functions are produced. More power must, however, be generated by the OHCs (about
      70-times the incoming). The end result is output which mimics quite closely the
      living basilar membrane's responses to low-intensity high-frequency tones.

PMID- 8567411
TI  - Distortion product otoacoustic emissions in rhesus (Macaca mulatta) monkey ears:
      normative findings.
AB  - Distortion product otoacoustic emissions (DPOAEs) in rhesus monkeys were
      characterized and the optimal parameters for their generation were determined.
      Robust DPOAEs were readily measurable from the ear canals of six rhesus monkeys
      (n = 12 ears). The nonmonotonic behavior of the f2/f1 ratio functions in rhesus
      monkeys was found to be similar to other animals and humans. The optimal mean
      f2/f1 ratio of 1.21 and the effect of the primary frequency and level on the
      optimal f2/f1 ratios were also similar to human measurements. The contour of the
      rhesus monkey DPOAE 'audiograms' and their behavior were also comparable to human
      measurements with slight differences in peak frequencies. The rhesus monkey DPOAE
      input/output (I/O) functions were generally monotonic with a slope approaching
      unity with increasing frequency. Therefore, our study shows that many basic DPOAE
      characteristics are remarkably similar in the two species and emphasizes the
      appropriateness of the rhesus monkey as a model for DPOAE research. Detailed
      studies of the behavior of DPOAEs can be carried out in a model that is
      phylogenetically close to human both in hearing and in the gross structure and
      histology of the inner ear.

PMID- 8567412
TI  - Glutathione protection against gentamicin ototoxicity depends on nutritional
      status.
AB  - This study demonstrates that gentamicin ototoxicity depends on dietary factors
      and correlates with tissue glutathione levels. After 15 days of gentamicin
      injections (100 mg/kg/day s.c.) guinea pigs on a regular protein diet (18.5%
      protein) had an average hearing loss of 9 dB at 3 kHz, 31 dB at 8 kHz and 42 dB
      at 18 kHz. Guinea pigs on a 7% protein diet showed an increased hearing loss of
      52 dB at 3 kHz, 63 dB at 8 kHz and 74 dB at 18 kHz. Supplementing the low protein
      diet with either essential or sulfur-containing amino acids did not protect
      against gentamicin ototoxicity. Glutathione levels in the cochlear sensory
      epithelium were decreased in animals on a low protein diet and could be restored
      to normal by oral administration of glutathione monoethyl ester (1.2 g/kg/day) in
      combination with vitamin C (100 mg/kg/day). Glutathione supplementation
      significantly reduced the magnitude of hearing loss in the low protein diet group
      at all frequencies (43 dB reduction at 3 kHz, 27 dB reduction at 8 kHz and 21 dB
      reduction at 18 kHz). In animals on a full protein diet, dietary glutathione
      neither increased cochlear glutathione levels nor attenuated hearing loss. Serum
      gentamicin levels did not differ between animals on the various diets with or
      without glutathione supplement. These results suggest that gentamicin toxicity
      and detoxifying mechanisms are affected by the metabolic state of the animal and
      the glutathione content of the tissue. Thus, compounds that could potentially
      protect against gentamicin ototoxicity may be more correctly assessed in animal
      models of deficient nutritional states in which endogenous detoxifying mechanisms
      are compromised. This animal model might also be more realistically related to
      the clinical situation of a critically ill patient receiving gentamicin
      treatment.

PMID- 8567413
TI  - Computerized digital photography in auditory research: a comparison of
      publication-quality digital printers with traditional darkroom methods.
AB  - Digital photography is the rapidly developing field of computer processing of
      images generated either directly from a digital camera or from scanned
      conventional film. Subsequent photographs output from digital color printers are
      publication-quality and superior to conventional darkroom prints because of
      greater image control (exposure, contrast, color correction). Because final print
      quality is the most critical factor in the research application of digital
      photography, we evaluated the photographic output of several continuous-tone
      digital printers. Digital images from selected microscopic sections of the middle
      and inner ear were generated by scanning black and white film and Ektachrome
      color transparencies and sent to commercial representatives for printing.
      Photographs from some printers were as good or better than traditional darkroom
      prints of the same film when evaluated for resolution, image quality, and costs.
      It is our hope that the hearing research field will benefit enormously by
      adoption of chemical-free digital photography because of its quality,
      convenience, speed, and low cost.

PMID- 8567414
TI  - Immunocytochemical localization of aspartate and glutamate in the peripheral
      vestibular system.
AB  - Controversy exists concerning the identity of the neurotransmitter in the
      mammalian peripheral vestibular system. Several candidates have been proposed,
      including the excitatory amino acids glutamate and aspartate and the inhibitory
      amino acid gamma-aminobutyric acid (GABA). Previous studies have demonstrated
      vestibuloneural electrophysiological activity associated with glutamate and
      aspartate. Paraffin sections of rat vestibular ganglia and end-organs were
      examined for the presence of glutamate-like and aspartate-like immunoreactivity.
      Our results demonstrate the presence of both aspartate-like and glutamate-like
      immunoreactivity in vestibular hair cells, peripheral vestibular nerve fibers,
      and vestibular ganglion cells. Minimal immunoreactivity was noted in the tissues
      surrounding these cells. These data add support to the hypothesis that the
      excitatory amino acids glutamate and aspartate are involved in vestibular
      neurotransmission.

PMID- 8567415
TI  - De novo synthesis of glucocorticoid hormone regulated inner ear proteins in rats.
AB  - Changes of rat inner ear de novo protein synthesis in response to dexamethasone
      (DEX), a synthetic glucocorticoid, have been analyzed by high resolution two
      dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D-SDS
      PAGE) and fluorography. Two proteins (M(r) 41,000 and 35,000) were amplified and
      one protein (M(r) 47,000) was suppressed by DEX in a cochlear culture medium. In
      the culture medium conditioned by vestibular tissue, three proteins (M(r) 67,000,
      57,000 and 50,000) were amplified after DEX administration. In cochlear and
      vestibular tissues, glucocorticoid-responsive protein synthesis was down
      regulated by DEX, including two proteins (M(r) 39,000 and 35,000) in the cochlea
      and five proteins (M(r) 80,000, 64,000, 59,000, 56,000 and 40,000) in the
      vestibule. The regulation of these inner ear proteins by DEX suggests that
      glucocorticoid may play an important role in normal inner ear microhomeostasis,
      as well as in the treatment of some inner ear disorders.

PMID- 8567416
TI  - Age-related changes in cochlear vascular conductance in mice.
AB  - Vascular changes contribute to age-related hearing loss but the mechanisms
      involved in microvascular reactivity, particularly in the aged ear, are still
      incompletely understood. In this study, possible age-related changes in cochlear
      blood flow (CBF) and vascular reactivity were studied in presbycusic mice
      (C57BL/6) and young, age-matched, and old controls (CBA/J) without presbycusis.
      Reactivity was monitored by laser Doppler flowmetry and assessed by change in
      cochlear vascular conductance (VC) (defined as the ratio of CBF to blood
      pressure) in response to round window-applied sodium nitroprusside, a
      vasodilating agent. Mean VC response of C57BL/6 mice differed from controls both
      in maximum response and in post-drug recovery time. In C57BL/6 mice, mean VC
      increased about 28%, in contrast to an increase of over 40% in young and age
      matched CBA/J controls. A less elevated VC response, similar to that of the
      presbycusic mice, was shown by aged (20-21 month) controls. Also, VC response in
      C57BL/6 mice was sustained throughout the 60 min observation period, while
      response of most CBA/J controls recovered in 50 min or less. These changes
      suggest age-dependent, pathologically-related altered responsiveness in cochlear
      vascular reactivity.

PMID- 8567417
TI  - The comparative effects of sodium thiosulfate, diethyldithiocarbamate, fosfomycin
      and WR-2721 on ameliorating cisplatin-induced ototoxicity.
AB  - The efficacies of four agents in ameliorating cisplatin-induced ototoxicity were
      investigated. Hamsters were given a series of 5 cisplatin injections (3
      mg/kg/injection once every other day, i.p.) either alone or in combination with
      1600 mg/kg/injection sodium thiosulfate (STS), 300 mg/kg/injection
      diethyldithiocarbamate (DDTC), 18 mg/kg/injection WR-2721, or 300 mg/kg/injection
      fosfomycin (n = 10/group). Ototoxicity was assessed electrophysiologically by
      auditory brainstem responses (ABRs) and anatomically by cochlear histology. The
      greatest auditory protection was given by STS, followed by DDTC. WR-2721 and
      fosfomycin did not provide any protection. All of the animals in the STS and DDTC
      groups survived, while some fatalities occurred in the fosfomycin, WR-2721, and
      cisplatin-only groups. Thus, the agents that were protective against ototoxicity
      were also protective against mortality. The ABRs also provided evidence of
      cisplatin-induced neuropathy. In summary, STS and DDTC hold promise for
      ameliorating the ototoxic effects of cisplatin chemotherapy and the hamster
      proved to be an excellent model of cisplatin ototoxicity.

PMID- 8567418
TI  - ATP modulation of L-type calcium channel currents in guinea pig outer hair cells.
AB  - Ca2+ channel currents and their modulation by adenosine 5'-triphosphate (ATP) in
      acutely isolated guinea pig outer hair cells (OHCs) were investigated using the
      whole-cell patch-clamp technique. The current-voltage (I-V) relation of OHCs
      indicated that the Ca2+ channel opened near -30 mV, and the current reached a
      maximum at +10 and 0 mV in 20 mM Ca2+ and Ba2+ external solutions, respectively.
      BayK 8644 (BayK, 2 microM) caused a 3.5-fold increase in peak Ca2+ currents and
      shifted the I-V curves toward more negative potentials. These results suggest
      that the majority of Ca2+ channels in OHCs have L-type characteristics. The
      effects of ATP on Ca2+ channels of OHCs were heterogenous. ATP (100 microM)
      decreased Ca2+ channel currents by 31.7 +/- 5.6% at 0 mV and shifted Ca2+ tail
      activation curves toward more depolarized potentials in some cells (N = 6). By
      contrast, in others, ATP enhanced the currents by 43.5 +/- 12.5% at +10 mV (N =
      6). In the presence of BayK, however, ATP-induced inhibition or enhancement of
      Ca2+ channel currents was attenuated. In addition, 100 microM ATP produced little
      effect on Ca2+ channel currents in another subpopulation of cells (N = 12). This
      heterogenous neuromodulation of Ca2+ channel currents by ATP may reflect a
      functional diversity among OHCs.

PMID- 8567419
TI  - Auditory cortex activity changes in long-term sensorineural deprivation during
      crude cochlear electrical stimulation: evaluation by positron emission
      tomography.
AB  - We studied three right-handed human volunteers who have been prelingually deaf
      for 16 to 26 years. We measured cerebral regional activity (rA) using 15O
      labelled water and positron emission tomography (PET) during rest and during
      electrical cochlear stimulation of the right ear. The stimulus consisted of crude
      constant current squared pulses, it is currently employed in cochlear implant
      screening. Two subjects described a subjective auditory sensation under cochlear
      stimulation, the third did not. An increment of the rA (which is linked to the
      regional cerebral blood flow) in the auditory cortex was observed in all
      subjects, activation was ipsilateral to stimulation in one subject and
      contralateral in two subjects. These findings suggest 1) that auditory pathways
      to the cortex can remain functional a long time after prelinguistic auditory
      deprivation, 2) that the auditory cortex can be activated by a crude electrical
      stimulation of the cochlea in the absence of perception of the auditory stimulus,
      3) that PET does not seem to offer any advantage for screening patients who have
      been prelingually deaf for a long time.

PMID- 8567420
TI  - Tectorial membrane regeneration in acoustically damaged birds: an
      immunocytochemical technique.
AB  - A novel immunocytochemical method was used to determine whether the sound-damaged
      adult quail ear can repair its tectorial membrane (TM) and to compare the repair
      in quail to that in chicks. Birds were exposed to an octave band noise with a
      center frequency of 1.5 kHz at 116 dB SPL for 4 h. The chicks were grouped based
      on recovery duration (0 and 7 days), while the quail were divided into 0-, 7-,
      and 14-day recovered groups. At the end of the recovery period, the animals were
      sacrificed, and their basilar papillae labeled with a TM-specific monoclonal
      primary antibody solution followed by a diaminobenzidine process. Examinations
      under a stereoscope revealed that a patch lesion devoid of TM was located on all
      0-day recovered papillae. Seven days later, a honeycomb-patterned layer was
      observed covering the lesion. In 14-day recovered quail ears, the honeycomb layer
      appeared similar to that seen at 7 days post-exposure. These observations
      indicated that both chicks and quail were able to repair their TM within 7 days
      following exposure to intense sound.

PMID- 8567421
TI  - Distortion-product otoacoustic emissions and their anaesthesia sensitivity in the
      European starling and the chicken.
AB  - The aim of the present experimental series was to provide further information on
      the distortion-product otoacoustic emissions (DP) of birds and contribute to a
      general understanding of DP generation. Basic characteristics of the DP 2f1-f2
      and 2f2-f1 were measured in the ear canal of both awake and anaesthetized
      European Starlings and chickens. The effect of a third suppressive tone and the
      behaviour of the DP under anaesthesia were also studied. In general, the DP
      characteristics of both bird species resembled those of lizards and mammals, but
      first appeared at somewhat higher primary-tone levels. The best frequencies of
      third tones suppressing 2f1-f2 lay near the first primary tone (f1), but for 2f2
      f1, the situation was more complex. Facilitation via a third tone was also seen
      for both DP, often at levels below those eliciting suppression. The DP 2f1-f2
      disappeared completely at the onset of deep anaesthesia and recovered to its
      original magnitude when the anaesthesia was lightened, sometimes with a
      considerable delay. The compound action potential (CAP) was somewhat more
      sensitive to anaesthesia than the DP. Control experiments showed that the
      anaesthesia effect was not a result of hypoxia. Avian DP at low and intermediate
      sound levels are thus physiologically-sensitive manifestations of normal hair
      cell function that are, in contrast to mammals, also anaesthesia-sensitive.

PMID- 8567422
TI  - Nerve fibres of the endolymphatic sac: electronmicroscopic findings in the
      Mongolian gerbil.
AB  - The presence of separate bundles of nerve fibres in the gerbilline endolymphatic
      sac (ES) is described, paying particular attention to their ultrastructure and
      localization. One bundle, localized in the area of the subepithelium which
      separates the sigmoid sinus from the ES, is composed only of myelinated fascicles
      which, moreover, seem to have an isolated contact with the ES area. Other two
      single nerve fibres, much smaller in caliber, are localized in the ES
      subepithelium and laterally to the ES area, still close to the sigmoid sinus.
      These fibres, composed of myelinated and unmyelinated fascicles, seem to have a
      rather longitudinal orientation and, moreover, contract close relationships with
      the rich vascular network of the ES subepithelial tissue. As far as the course is
      concerned, the serial sectioning technique would suggest that the nerve fibres
      get very close to the ES epithelial cell layer, going proximal to distal.
      Speculations on the origin of this nerve contingent in the ES are proposed and
      discussed in view of possible new theories for pathogenesis and therapy of some
      inner ear diseases.

PMID- 8567423
TI  - ATP-induced increase in intracellular Ca2+ concentration in the cultured marginal
      cell of the stria vascularis of guinea-pigs.
AB  - The primary culture of marginal cells from the explant of the stria vascularis of
      guinea-pigs was established and confirmed by morphological, immunohistochemical
      and physiological characters of the cultivated cells. The positive stain of
      cytokeratin 18 without vimentin and desmin expressions indicated the epithelial
      origin of the cultured polygonal cells. Electron microscopical findings of
      cultured cells resembled the morphological characteristics of marginal cells. The
      addition of 100 microM ouabain to the cultured cells significantly increased the
      intracellular Na+ concentration, providing the evidence for the presence of Na+
      pump. Using the cultured marginal cells identified by the above-mentioned
      findings, the effects of neurotransmitters and hormones in regulating
      intracellular Ca2+ concentration ([Ca2+]i) were investigated. The addition of 10(
      4) M ATP caused an increase in [Ca2+]i, which was independent of the presence of
      extracellular Ca2+. The rank order of agonist potency was ATP > alpha, beta
      methylene ATP > ADP. Adenosine, however, evoked no response. Cultured marginal
      cells may possess P2-purinergic receptors which mobilize Ca2+ from the
      intracellular Ca2+ pool.

PMID- 8567424
TI  - Deafness induced cell size changes in rostral AVCN of the guinea pig.
AB  - The right cochleae of 250-350 g guinea pigs were lesioned by topical
      administration of neomycin in the middle ear cavity. Eight weeks after the
      lesion, the cochleae and cochlear nuclei were analyzed. Cochlear hair cell loss
      was assessed, and cell areas of spherical bushy cells in the rostral
      anteroventral cochlear nucleus (AVCN) were compared between the lesioned and
      normal hearing sides for each animal. In five animals with both inner and outer
      hair cell loss in the lesioned cochlea, the average area of neuronal somata in
      the rostral AVCN in the lesioned side was 22% smaller than the average area of
      these cells in the normal hearing side. In two animals with outer hair cell loss
      but inner hair cells remaining, there was no difference in cell size between the
      lesioned and non-lesioned AVCN. These results provide evidence that there is
      significant shrinkage in AVCN cell size in the mature mammal after hearing loss
      associated with inner hair cell loss.

PMID- 8567425
TI  - Endocytosis and transepithelial transport of endolymph in the endolymphatic sac.
AB  - The fate of cationized ferritin (CF) injected into the endolymphatic space of the
      endolymphatic sac was observed by transmission electron microscopy. At 10 min
      after the injection, CF particles bound to the apical plasma membrane of
      epithelial cells of the sac and were then endocytosed with coated pits. However,
      they never passed through the junctional complexes between the epithelial cells.
      At 30 min after the injection, the CF particles were transferred to endosomes and
      lysosomes by small vesicles of 100-150 nm in diameter. CF particles were also
      found in small vesicles close to Golgi cisternae and in multivesicular bodies.
      Acid phosphatase positive lysosomes were found close to endosomes containing CF
      particles. In addition, a small fraction of the small vesicles containing CF
      particles became inserted into the basolateral plasma membrane. At 60 min after
      the injection, many CF particles were found in acid phosphatase positive
      secondary lysosomes. These observations suggest that endocytosis of endolymph is
      actively performed by the epithelial cells of the sac, and transepithelial
      vesicular transport across the epithelial cells occurs.

PMID- 8567426
TI  - Calcium-binding proteins in the spiral ganglion of the monkey, Callithrix
      jacchus.
AB  - Calcium-binding proteins can act as intermediaries between changing levels of
      free intracellular calcium ions and the physiological response of neurons. Some
      of these proteins, among them calbindin (CB), calretinin (CR) and parvalbumin
      (PV), can act as calcium buffers. A survey of previous studies in rodents and
      human fetuses leads to the impression that many spiral ganglion cells co-express
      CB, CR, and PV. The findings of the present study suggest that, in the adult
      marmoset, the expression of CB is restricted to a small number of cells, most
      likely type II ganglion cells, and that at least some of the numerous type I
      ganglion cells co-express CR and PV. In the neonate marmoset, large numbers of
      putative type I ganglion cells from the apical cochlear turn transiently
      expressed a light and granular labeling for CB-like immunoreactivity, in addition
      to the cells we believe to be type II ganglion cells exhibiting a strong and
      solid CB-like staining. The spiral ganglion cells in all developmental stages co
      expressed the mitochondrial enzyme cytochrome oxidase. Furthermore, a small
      population of CB-LI axons of unknown origin was found to terminate near the CB
      immunoreactive ganglion cells.

PMID- 8567427
TI  - Nitroprusside suppresses cochlear potentials and outer hair cell responses.
AB  - Biochemical and pharmacological evidence supports a role for nitric oxide (NO) in
      the cochlea. In the present experiments, we tested sodium nitroprusside (SNP), an
      NO donor, applied by intracochlear perfusions on sound-evoked responses of the
      cochlea (CM, cochlear microphonic; SP, summating potential; EP, endocochlear
      potential; CAP, compound action potential) and in vitro on outer hair cell (OHC)
      voltage-induced length changes and current responses. In vivo application of SNP
      in increasing concentrations (10, 33, 100, 330 and 1000 microM) reduced all sound
      evoked responses starting at about 300 microM. The responses continued to decline
      after a postdrug wash. At 1 mM SNP decreased EP slowly (approximately 80 min)
      whereas at 10 mM it reduced EP more rapidly (approximately 20 min). Ferricyanide
      (1 mM) and S-nitroso-N-acetylpenicillamine (SNAP; 1 mM) had no effect on sound
      evoked cochlear potentials. Ferricyanide (1 mM and 10 mM) and ferrocyanide (10
      mM) had no effect on EP. In vitro, SNP (10 mM) significantly reduced both OHC
      voltage-induced length changes and whole-cell outward currents. Results suggest
      that SNP, possibly acting by released NO, influences cochlear function through
      effects at the stria vascularis and at the OHCs.

PMID- 8567429
TI  - Vowel and vowel sequence processing by cochlear nucleus neurons.
AB  - This study examined neuronal discharge rates and temporal patterns to vowels and
      vowel sequences in chinchilla. The properties of primary-like, chopper, and onset
      neurons were studied using vowels /i/, /a/, and /u/ individually and paired with
      separations (0-100 ms), at sound levels above and below thresholds. The
      interspike interval, period, and post-stimulus-time histograms of all neuronal
      types to a vowel were modified when in a sequence. Primary-like and chopper
      discharges were reduced and enhanced depending on vowel sequence parameters;
      onset neurons exhibited discharge rate reductions only and not enhancements. In
      addition to rate changes, novel discharge intervals appeared with vowel pairs. An
      unexpected finding on choppers was that subthreshold levels of the preceding
      vowel in a paired sequence enhanced discharges to the succeeding one. Reducing
      levels of preceding or increasing levels of following vowels evoked changes not
      predictable from single vowel data. Thus the responses to paired vowels in a
      sequence are interactive. Patterns of discharges and rate functions to vowel
      sounds from neurons of the same type varied greatly. The cochlear nuclei harbor
      anatomically and functionally diverse neurons. Because of this heterogeneity, the
      neural transformations of vowel segments by all cochlear nucleus neuronal types
      can not be predicted from sinusoidal data.

PMID- 8567428
TI  - Auditory brainstem responses of CBA/J mice with neonatal conductive hearing
      losses and treatment with GM1 ganglioside.
AB  - Exogenous administration of GM1 ganglioside to CBA/J mice with a neonatal
      conductive hearing loss ameliorates the atrophy of spiral ganglion neurons,
      ventral cochlear nucleus neurons, and ventral cochlear nucleus volume. The
      present investigation demonstrates the extent of a conductive loss caused by
      atresia and tests the hypothesis that GM1 ganglioside treatment will ameliorate
      the conductive hearing loss. Auditory brainstem responses were recorded from four
      groups of seven mice each: two groups received daily subcutaneous injections of
      saline (one group had normal hearing; the other had a conductive hearing loss);
      the other two groups received daily subcutaneous injections of GM1 ganglioside
      (one group had normal hearing; the other had a conductive hearing loss). In mice
      with a conductive loss, decreases in hearing sensitivity were greatest at high
      frequencies. The decreases were determined by comparing mean ABR thresholds of
      the conductive loss mice with those of normal hearing mice. The conductive
      hearing loss induced in the mice in this study was similar to that seen in humans
      with congenital aural atresias. GM1 ganglioside treatment had no significant
      effect on ABR wave I thresholds or latencies in either group.

PMID- 8567430
TI  - Auditory pathway plasticity in adult humans after unilateral idiopathic sudden
      sensorineural hearing loss.
AB  - We recorded auditory evoked magnetic fields from 8 patients with unilateral,
      idiopathic, sudden, sensorineural hearing loss and from 8 healthy controls, using
      a 122-channel whole-scalp neuromagnetometer. The stimuli were 50-ms l-kHz tone
      bursts, delivered to the healthy ear at interstimulus intervals (ISIs) of 1, 2,
      4, 8, and 16 s. On average, as in normal-hearing controls, the dipole moments and
      the latencies of N100m, the 100-ms response, increased as a function of ISI over
      both hemispheres to left- and right-ear stimulation. Four patients had shorter
      response latencies and 4 had stronger dipole moments over the hemisphere
      ipsilateral to the stimulation. In 3 patients, one additional source was observed
      over the anterolateral right hemisphere and another near head midline. These
      findings suggest that unilateral sensorineural hearing loss may modify
      information processing in the central auditory pathways.

PMID- 8567431
TI  - Projections of the individual vestibular end-organs in the brain stem of the
      squirrel monkey.
AB  - The central nervous system (CNS) projections of primary afferent neurons from
      individual vestibular receptors were studied using horseradish peroxidase (HRP)
      or biocytin labeling in 14 ears from 7 adult squirrel monkeys using the technique
      developed in the chinchilla (Lee et al., 1989, 1992). The specificity of labeling
      was verified by examining the location of the labeled fibers and cell bodies in
      the vestibular nerve and Scarpa's ganglion. Labeled fibers and cells were
      restricted to nerves and areas belonging to groups of cells in either the
      superior or the inferior ganglion of the vestibular nerve. In the vestibular
      nerve root, labeled primary afferent fibers also exhibited a receptor-dependent
      segregation at the entrance to the medulla. Fibers from the HSC and the SSC were
      found rostrally and those from the PSC and the SAC were found in the caudal area.
      The UTR fibers were situated intermediate between these two groups of fibers. (A
      bundle of fibers, probably vestibular efferents, was identified immediately
      rostrally and ventromedially to the UTR fibers.) The primary afferent fibers
      bifurcated into secondary ascending and descending fibers at the lateral border
      of the vestibular nuclei, forming a longitudinal rostrocaudal vestibular tract.
      The secondary fibers from individual end-organs occupied specific locations in
      the tract: the UTR fibers were dorsal to the SSC and the HSC fibers, PSC fibers
      were found most medially, and the SAC fibers occupied the lateralmost area. The
      secondary UTR fibers overlapped considerably with those of the SSC and the HSC.
      The orderly receptor-dependent segregation of fibers was more prominent in the
      descending tracts than in the ascending tracts. In the vestibular nuclei complex
      the location of the tertiary branches of various end-organs exhibited
      considerable overlap within the major vestibular nuclei (SN, superior nucleus;
      LN, lateral nucleus; MN, medial nucleus; DN, descending nucleus). There were
      still differences, however, in the projection pattern. Fibers from the SAC ran
      primarily in the lateral area, fibers from the SSC and the UTR were found
      ventromedially to the SAC fibers, and the HSC projected slightly medially to the
      fibers from the SSC. The PSC fibers projected most medially. The UTR and SAC sent
      numerous fibers to the cerebellum. Fibers from the semicircular canals projected
      through the rostrodorsal region of the SN and presumably also projected to the
      cerebellum. The precise termination of fibers was evaluated by studying the
      location of labeled boutons, which were identified in all major vestibular
      nuclei. Labeled boutons from all the receptors were in the rostral and central
      areas of the SN, and in the MN mainly in the rostral two-thirds. In the LN,
      boutons from all the receptors were in the rostroventral part, most of which were
      from the UTR and SAC. No labeled boutons were in the caudodorsal part of this
      nucleus. Labeled boutons in the DN primarily surrounded the descending tract
      fibers and were particularly prominent medially. In specimens in which superior
      vestibular nerve receptor organs were scratched vestibular efferent fibers were
      also labeled. These fibers traveled in the most ventral part of the vestibular
      nerve root and projected in the ventral aspect of the LN to labeled soma in the
      ipsilateral and contralateral brain stem. Specificity the in projection patterns
      of efferent fibers from different end-organs could not be ascertained.

PMID- 8567432
TI  - Comodulation masking release in a songbird.
AB  - Comodulation masking release (CMR) describes the reduced masking of a pure tone
      when the masking is a noise that is coherently amplitude modulated (comodulated)
      over the total range of the spectrum compared to masking by an unmodulated noise
      of the same bandwidth and overall energy. The masking release results from cues
      available within a critical band and from cues generated by comparisons across
      critical bands ('true' CMR). Here we report data on masking release and 'true'
      CMR in a songbird, the European starling (Strunus vulgaris), that was
      demonstrated in a psychoacoustic experiment using a GO/NOGO paradigm. Masked
      thresholds for 2-kHz tones centered in digitally generated continuous masking
      noise of different bandwidths were determined, and the amount of masking release
      was calculated as the threshold difference between the unmodulated and the
      comodulated condition. In the first experiment the modulator was a 50-Hz lowpass
      noise. A masking release of 11.8 dB was found for the noise masker with the
      largest bandwidth (1600 Hz). With the masker bandwidth decreasing to 50 Hz, the
      birds' release from masking was reduced to 1.6 dB. The starling's 'true' CMR was
      4 dB or 8 dB, depending on the definition that was applied. In a second
      experiment the masker bandwidth was constant (1600 Hz) and the cut-off frequency
      of the modulator was varied. A release from masking of 17.8 dB was found for a
      modulator cut-off frequency of 12.5 Hz. It decreased to 6.1 dB with an increase
      in the modulator cut-off frequency to 400 Hz. The duration of the test signal
      (100-750 ms) had little effect on the release from masking. Given the
      similarities in the release from masking and in CMR of starlings and humans, the
      starling may provide an excellent model for studying the mechanisms that underlie
      the generation of CMR.

PMID- 8567433
TI  - Effect of cisplatin administration on the electrochemical composition of
      endolymph in the rat cochlea.
AB  - The effect of cisplatin on the electrochemical composition of the cochlear
      endolymph was studied in Long-Evans rats three days after a single
      intraperitoneal injection (8 mg/kg b.w.). A dose 2/3 of LD50 induced a decrease
      of the endolymphatic concentration of potassium whereas the endocochlear
      potential was unaffected. The discrepancy between these two findings indicated
      that cisplatin did not alter the mechanisms involved in the genesis of the
      endocochlear potential but modified the passive K transport into endolymph.

PMID- 8567434
TI  - Fimbrin expression in the developing rat cochlea.
AB  - The expression of fimbrin in the developing rat cochlea was analyzed using an
      immunohistochemical technique with fimbrin antibody. The cochlea displayed
      temporal and lateral-longitudinal gradients for fimbrin expression during
      development. Fimbrin immunoreactivity first appeared in the inner hair cell
      stereocilia of the basal turn on the first gestational day studied (day 18). At
      birth, both inner (IHC) and outer hair cell (OHC) stereocilia of the basal turn
      showed positive labeling with fimbrin antibody. The progression of appearance was
      always from IHCs to OHCs and fimbrin immunostaining appeared in the apical hair
      cells by postnatal day 6. Immunostaining was restricted to stereocilia and the
      cuticular plate, and no immunoreactivity was observed in neighboring structures
      of the epithelium. Double labeling using both fimbrin antibody and phalloidin
      binding revealed similar chronological expression from the earliest stage
      studied. Increasing fimbrin immunoreactivity was observed in hair cells until
      late postnatal and adult stages. This study suggests that fimbrin is expressed
      with F-actin during development and fimbrin together with actin may constitute
      the two basic molecules that participate in stereocilia formation. We speculate
      that fimbrin may help maintain the parallel growth of actin filaments within the
      stereocilia. These data additionally support previous findings that hair cell
      maturation occurs from the base to the apex and from IHCs to OHCs.

PMID- 8567435
TI  - Potential distributions and neural excitation patterns in a rotationally
      symmetric model of the electrically stimulated cochlea.
AB  - In spite of many satisfactory results, the clinical outcome of cochlear
      implantation is poorly predictable and further insight into the fundamentals of
      electrical nerve stimulation in this complex geometry is necessary. For this
      purpose we developed a rotationally symmetric volume conductor model of the
      implanted cochlea, using the Boundary Element Method (BEM). This configuration
      mimics the cochlear anatomy more closely than previous, unrolled models. The
      calculated potential distribution in the cochlea due to stimulating electrodes is
      combined with a multiple non-linear node model of auditory nerve fibres, which we
      recently developed. The combined model is used to compute excitation profiles of
      the auditory nerve for a variety of stimulus levels and electrode positions. The
      model predicts that the excitation threshold, the spatial selectivity and the
      dynamic range depend on the exact position of the electrode in the scala tympani.
      These results are in good agreement with recently published electrical ABR data.
      It is shown that the use of actively modelled nerve fibres is essential to obtain
      correct predictions for the biphasic stimuli typically used in cochlear implants
      and that unrolling the cochlear duct as done in previous models leads to
      erroneous predictions regarding modiolar stimulation.

PMID- 8567436
TI  - The osmotic response of the isolated, unfixed mouse tectorial membrane to
      isosmotic solutions: effect of Na+, K+, and Ca2+ concentration.
AB  - Changes in the size, shape, and structure of the isolated tectorial membrane (TM)
      of the mouse were measured in response to isosmotic changes in the ionic
      composition of the bathing solution. Substitution of artificial perilymph (AP)
      for artificial endolymph (AE) caused a small (approximately 1%) shrinkage of the
      TM's thickness. This substitution alters not only the predominate cation (from K+
      to Na+) but also the Ca2+ concentration (from 20 mumol/l to 2 mmol/l). When the
      predominate cation was changed from K+ to Na+, while holding Ca2+ concentration
      constant, results depended on Ca2+ concentration: there was a small
      (approximately 1%) swelling for 20 mumol/l Ca2+, larger (approximately 14%)
      swelling for lower (< 7 mumol/l) concentrations of Ca2+, and little response for
      2 mmol/l Ca2+ or for solutions containing the Ca2+ chelator EGTA. Addition of
      Ca2+ while holding the predominate cation constant caused shrinkage of the TM;
      both removal of Ca2+ and addition of the Ca2+ chelator EGTA caused swelling.
      Swelling responses were largely reversible if the magnitude of the swelling was
      small. Responses greater than a few percent were only partially reversible and
      caused long-lasting changes. Changes in ionic composition of the bath affected
      not only the thickness of the TM but also its other dimensions. Solution changes
      that increase TM thickness tend to cause radial shearing motions of the surfaces
      of the TM, which are accompanied by small decreases in width. Little change in
      length was observed. Although the responses were non-isotropic, increases in
      thickness were highly correlated with increases in volume. Swelling of the TM was
      also accompanied by a reduction in prominence of its radially oriented fibrillar
      structure. These results for the isolated TM of the mouse are qualitatively
      similar to those obtained previously for the isolated chick TM (Freeman et al.,
      1994) but different from those obtained for the in vitro mouse TM (Kronester
      Frei, 1979a).

PMID- 8567437
TI  - Age-related changes in auditory evoked potentials of gerbils. III. Low-frequency
      responses and repetition rate effects.
AB  - The auditory brainstem response (ABR) was recorded non-invasively from Mongolian
      gerbils ranging in age from 6 to 36 months. The ABR was elicited using gaussian
      tone bursts at octave intervals from 1 to 16 kHz. Responses were bandpass
      filtered from 30 to 300 Hz (LF-ABR; low-frequency component) and from 300 to 3000
      Hz (HF-ABR; high-frequency component). In Experiment A, the thresholds of the two
      components (HF- and LF-ABR) were compared in 6- and 36-month subjects. The LF-ABR
      varied more with age than did the HF-ABR, particularly at stimulus frequencies of
      2 kHz and above. As shown previously for the HF-ABR, the latencies of the LF-ABR
      increased as a function of hearing loss in aged gerbils whereas amplitudes of the
      LF-ABR were reduced in all aged gerbils, regardless of age-related threshold
      elevation. In Experiment B, tone bursts were presented at rates of 11-91/s to
      gerbils aged 6, 18, 30, and 36 months. Increased repetition rate resulted in an
      increase in the latency of both the HF- and LF-ABR, but to the same degree in
      each age group. Similarly, the interpeak intervals of the HF-ABR increased as a
      function of repetition rate in all subjects to the same degree. Increased age and
      increased repetition rate both resulted in significant reductions in ABR
      amplitudes, but rate did not interact with age. The data suggest that (1) the LF
      ABR may be more sensitive to aging than is the HF-ABR and (2) there are no age
      related changes in the HF- or LF-ABR which are dependent upon the repetition
      rate.

PMID- 8567438
TI  - Time course of axonal myelination in the human brainstem auditory pathway.
AB  - Structures in the human brainstem auditory pathway, from the proximal end of the
      cochlear nerve to the inferior colliculus, undergo myelination between the 26th
      and 29th fetal weeks. By the 26th week of gestation, axons in the cochlear nerve
      and brainstem pathways have acquired linear arrays of oligodendrocytes, and faint
      myelin sheaths can be distinguished. By the 29th week, definitive myelination is
      present in all auditory pathways, including the proximal end of the cochlear
      nerve, trapezoid body, lateral lemniscus, dorsal commissure of the lemniscus,
      commissure of the inferior colliculus and brachium of the inferior colliculus.
      Subsequent to the 29th gestational week, density of myelination increases in all
      pathways until at least 1 year postnatal age. The time of onset of myelination
      coincides with the onset of acousticomotor reflexes and brainstem auditory evoked
      responses, processes which depend on rapid, synchronized conduction of auditory
      impulses in the cochlear nerve and brainstem. The cotemporality in appearance of
      myelin, reflex responses, and evoked responses supports the idea that the 26th to
      28th gestational weeks are a critical period in the onset of human central
      auditory function. The subsequent increase in myelin density is likely to be a
      factor in the steady decrease in ABR wave III-V latencies observed during the
      perinatal period.

PMID- 8567439
TI  - Glucocorticoid receptor expression in the postnatal rat cochlea.
AB  - The glucocorticoid receptor (GR) expression in the neonatal rat cochlea was
      investigated by utilization of a polyclonal antibody against GR, the
      immunoreactivity of which exhibited a distinct, age-dependent developmental
      pattern in tissues of the spiral ligament (SL). Immunostaining of GR appeared
      initially at the 7th postnatal day (PND), increased rapidly between the 14th and
      21st PND, and reached adult-like expression levels by the 21st PND. Less
      pronounced, developmentally regulated expression patterns of GR were observed in
      cells of the spiral limbus (SLi), spiral ganglion (SG), organ of Corti (OC), and
      cochlear nerve (CN). For example, high expression levels of GR were observed in
      the SLi, SG and OC at 3 PND; subsequently, GR immunoreactivity levels decreased
      from 7 to 14 PND, and then GR immunoreactivity intensified in these regions by 21
      PND. No remarkable changes in GR expression were observed in stria vascularis
      (SV). These data indicate that GR expression in the inner ear is tissue and age
      specific, and that GR expression parallels both Na,K-ATPase expression and
      endocochlear potential development.

PMID- 8567440
TI  - Carbohydrate distribution in the living utricular macula of the guinea pig
      detected by lectins.
AB  - Carbohydrate distribution in the fresh utricular macula of the guinea pig was
      analysed using lectins such as Concanavalin A (ConA), Dolichos biflorus
      agglutinin (DBA), peanut agglutinin (PNA), soybean agglutinin (SBA), Ulex
      europeus agglutinin (UEA-1) and wheat germ agglutinin (WGA) by means of confocal
      laser scanning microscopy. The ciliary bundle was strongly reactive to ConA, PNA,
      SBA and WGA but not to DBA and UEA-I, showing that the ciliary bundle has
      abundant D-galactose (GaI), N-acetyl-D-glucosamine (GlcNAc), D-mannose (Man) and
      sialic acid(s) (Sia) but not detectable amounts of L-fucose (Fuc) and terminal N
      acetyl-D-galactosamine (GalNAc). Similar patterns of lectin bindings with
      moderate-to-weak intensities were observed on the non-cilial apical surface, on
      the surface of the otoconia and in the gelatinous layer of the otoconial
      membrane. On the contrary, the globular substance, a precursor of the otoconia,
      was scarcely reactive to any lectin examined, implying that it lacks
      glycoconjugates on its surface. Previous histochemical studies reported that the
      otoconial membrane possesses a much higher affinity for lectins that does the
      sensory epithelium (including the cilia) in the vestibular organ. This
      discrepancy suggests that factors in the preparation process may affect the
      otoconial membrane or the surface coat of the cilia to change their lectin
      affinity. Meanwhile, sialidase treatment augmented the affinity of the ciliary
      bundle for DBA and PNA, indicating that sialylated GalNAc and Gal are present on
      the vestibular ciliary bundle.

PMID- 8567441
TI  - Caffeine-induced shortening of isolated outer hair cells: an osmotic mechanism of
      action.
AB  - The application of caffeine to the bathing medium of isolated cochlear outer hair
      cells (OHCs) induces shortening of the cells (Slepecky et al., 1988). This study
      was designed to test the hypothesis that a 'smooth muscle-like' mechanism was
      responsible for the caffeine-induced shortening of OHCs as suggested by Slepecky
      et al. OHCs were isolated from guinea pig cochleae and length measurements were
      taken during various drug perfusions. Antagonists of the ryanodine
      receptor/Ca(2+)-induced Ca2+ release (CICR; tetracaine, ruthenium red, and
      ryanodine) failed to block the caffeine-induced shortening of the OHCs.
      Application of the Ca2+ ionophore A23187 caused cell length to increase. These
      results did not support this hypothesis and therefore, an osmotic mechanism was
      proposed.

PMID- 8567442
TI  - Evidence that glutathione is the unidentified amine (Unk 2.5) released by high
      potassium into cochlear fluids.
AB  - An unidentified substance, Unk 2.5, may be important in the function of the
      cochlea. The efflux of Unk 2.5 into cochlear fluids is increased by intense sound
      (Bobbin and Fallon, 1992) and by exposure of the cochlear tissue to high
      concentrations of K+ (Bobbin et al., 1990,1991; Bobbin and Fallon, 1992). The
      unidentified chemical eluted at 2.5 min in chromatograms obtained by HPLC
      utilizing fluorescence detection and precolumn o-phthalaldehyde (OPA)
      derivatization of samples of effluent from the cochlea (e.g., Bobbin et al.,
      1990). The purpose of this investigation was to provide evidence as to the
      identity of this unidentified chemical we call Unk 2.5. Therefore, we carried out
      additional HPLC assays on samples obtained during perfusion of the cochlear
      perilymph compartment. Glutathione (GSH) was found to elute at the same time (@
      2.5 min) as Unk 2.5 in HPLC chromatograms utilizing precolumn derivatization with
      OPA and mercaptoethanol. In addition, both Unk 2.5 and GSH reacted with OPA
      without mercaptoethanol present in the reaction mixture to give a peak at 2.5 min
      in the chromatogram, but failed to show this peak if stored in solutions with a
      pH > 7 for several days before the reaction. Results indicate that Unk 2.5 is GSH
      or a closely related compound. Given this probable identification GSH, aka Unk
      2.5, has been demonstrated to be released from tissue in the cochlea by high
      concentrations of K+ (Bobbin et al., 1990,1991) and by intense sound (124 dB SPL;
      Bobbin and Fallon, 1992).

PMID- 8567443
TI  - Effect of interstimulus interval on evoked otoacoustic emissions.
AB  - In order to explore extensively the effect of interstimulus interval, including
      very short interstimulus intervals, on evoked otoacoustic emissions (EOAEs),
      several EOAE recordings were carried out using pairs of clicks: a suppressor
      click preceded the stimulus click generating an EOAE, with various intervals
      between the two clicks. EOAEs elicited by two clicks separated by intervals under
      8-9 ms had significantly smaller amplitudes than EOAEs evoked by the stimulus
      alone. The amplitude decay correlated with the interclick interval, and was about
      40% when the interclick interval decreased from 12 to 1 ms. This phenomenon has
      been noted before but not precisely quantified. It might reflect an adaptive
      mechanism within the outer hair cells, which has been previously described, or
      else mechanical interactions on the basilar membrane. The delay in EOAE decrease
      is of the same order as the first phase of neural adaptation, known as 'rapid
      adaptation', and these thus may prove to be correlated.

PMID- 8567444
TI  - Two types of calcium channels in bullfrog saccular hair cells.
AB  - Ca2+ channels were studied in cell-attached recordings from the basolateral
      membrane of the bullfrog saccular hair cells with the EPC-9 patch-clamp system.
      Pipettes contained 110 mM Ba2+ and the membrane potential was zeroed with
      isotonic potassium aspartate. Data acquisition and analysis were performed using
      E9SCREEN and M2LAB software. L-type channel was distinguished by a single-channel
      conductance of 26 pS, activation range between -10 and +40 mV and intense
      activity even at a holding potential of -40 mV. The L-type channel showed
      characteristic bursts of brief openings (mode 1) interrupted occasionally by
      longer openings (mode 2). Bay K 8644 promoted the mode 2 activity and nifedipine
      inhibited L-type channel activity. Another type of calcium channels, 20 pS
      channel, was detected by -50 to +10 mV depolarizing steps from a holding
      potential of -40 or -80 mV. This channel was insensitive to dihydropyridines and
      resembled the N-type channel.

PMID- 8567445
TI  - Enkephalin-like immunoreactivity in the chick brainstem: possible relation to the
      cochlear efferent system.
AB  - Mammalian lateral olivocochlear (LOC) neurons that are immunoreactive for choline
      acetyltransferase (ChAT) are also immunoreactive for enkephalin (Enk). To
      determine whether cochlear efferent neurons in birds might also contain Enk-like
      immunoreactivity (Enk-LI), we studied the auditory brainstem of the domestic
      chicken using antisera to ChAT, leucine-enkephalin (L-Enk) and methionine
      enkephalin (M-Enk). Enk-LI terminals are found around, but not within, the
      superior olivary nucleus (SO) and the nucleus of the lateral lemniscus, pars
      intermedia (LLi). A moderate concentration of Enk-LI terminals is found
      ventromedial to the ventral facial nucleus (VIIv) where the ventrolateral group
      of ChAT-I cochlear efferent neurons is located. After colchicine injections into
      the lateral ventricle, a population of intensely stained Enk-LI perikarya was
      found in the nucleus of the lateral lemniscus, pars ventralis (LLv) with
      scattered cells in the LLi and the nucleus subceruleus ventralis (SCv). The
      distribution of Enk-LI and ChAT-I somata, however, never overlapped, even in
      adjacent sections. Thus, in the chick, Enk-LI perikarya are not distributed in
      areas where cochlear efferent neurons are found. Instead, a dense concentration
      of Enk-I terminals can be found in areas containing ChAT-I cochlear efferent
      neurons. The source of these enkephalinergic terminals may be a population of Enk
      LI cells in the LLv.

PMID- 8567446
TI  - Decreased inhibition to lateral superior olive neurons in young and aged Sprague
      Dawley rats.
AB  - Lateral superior olive (LSO) neurons in young and aged Sprague-Dawley rats have
      functional properties consistent with a limited contralateral inhibition, which
      is markedly different from other animals. An unusually low proportion of LSO
      cells (36/113) exhibited contralateral inhibition (and ipsilateral excitation,
      IE), while over 25% of LSO units exhibited excitatory responses to contralateral
      stimuli. Inhibition of most IE LSO neurons was evident only when the
      contralateral intensity was greater than the ipsilateral intensity, resulting in
      a marked shift in sensitivity to interaural intensity differences (IID). The
      firing rate of IE neurons was also affected more by a change in intensity of
      ipsilateral compared to contralateral stimuli. The shift in the IID sensitivity
      and the relative decrease in effectiveness of contralaterally driven inhibition
      in Sprague-Dawley rat LSO neurons could be due to decreased inhibitory inputs
      from the MNTB principal cells, increased contralateral excitatory effects and/or
      increased ipsilateral excitatory effects. Age-related decreases in the numbers of
      MNTB neurons observed anatomically is not reflected in a change in LSO function.
      The Sprague-Dawley rat may be a useful model for the effect of reduced inhibition
      in the superior olivary complex on auditory behavior.

PMID- 8567447
TI  - Detection of beta-actin mRNA by RT-PCR in normal and regenerating chicken
      cochleae.
AB  - Reverse transcriptase polymerase chain reaction (RT-PCR) was used to show that
      beta-actin RNA levels can be detected in total RNA isolations from as few as two
      cochleae. In functionally mature chicken cochleae, a low homeostatic level of
      beta-actin message should be expressed in order to synthesize enough actin to
      maintain the stereocilia, cuticular plate, junctional complexes of hair cells and
      the cytoskeletal components of the supporting cells. The RT-PCR product obtained
      has been characterized by size, restriction digest analysis, and DNA sequencing
      analysis. These procedures have confirmed that the product is amplified from a
      chicken beta-actin mRNA target. Subsequently, semi-quantitative RT-PCR techniques
      were used to demonstrate an upregulation of beta-actin mRNA transcription levels
      in the cells of the basilar papilla during regeneration following damage from
      acoustic overstimulation. These studies suggest that RT-PCR can be utilized for
      analysis of limited quantities of tissue such as that found in the chicken
      cochlea and indicate promise for further qualitative and quantitative studies on
      the molecular mechanisms of hair cell transduction and regeneration.

PMID- 8567448
TI  - Binaural noise suppresses linear click-evoked otoacoustic emissions more than
      ipsilateral or contralateral noise.
AB  - We studied the efferent suppression of click-evoked otoacoustic emissions with 65
      dB SPL of white noise presented to left, right, or sometimes both, ears for 408
      ms. Each burst of noise preceded a series of four unipolar 80 microseconds 65 dB
      peak Sound Pressure clicks, presented to the left ear only. The first click of
      the four-click group followed the end of the noise by either 1, 2, 5, 10, 20, 50,
      100 or 200 ms; each subsequent click was offset by 20 additional ms via an ILO88
      system with special programming modifications. Conditions were alternated so that
      a 'without noise' condition preceded a 'with noise' condition for three
      repetitions of 600 clicks per trial. Seven subjects with normal hearing
      participated in the study, and three of the seven participated in a test-retest
      reliability study. Results showed the greatest suppression followed binaural
      stimulation ending within one to five ms of the first click in the pulse train.
      Somewhat less suppression was seen following ipsilateral stimulation. The least
      amount of suppression was seen following contralateral stimulation, suggesting
      that previous research using contralateral stimulation may underestimate efferent
      effects. We saw no effects when the end of the noise was 100 ms or more away from
      the beginning of the click train.

PMID- 8567449
TI  - Lyman J. Bratzler, 1905-1976: a brief biography.

PMID- 8567450
TI  - Sperm production in boars after nine generations of selection for increased
      weight of testis.
AB  - Body, testis, and epididymis weights were recorded and homogenization-resistant
      sperm nuclei were counted to determine daily sperm production and the number of
      sperm stored within the cauda epididymis (CAUDASP) in 145 boars of a control line
      (C) and 128 boars of a line selected for increased predicted weight of testis
      (TS) at 150 d of age. Random samples of boars were evaluated at five ages between
      70 and 450 d in Generation 8 and 15 ages between 70 and 296 d in Generation 9.
      Data were analyzed using an animal model that included the fixed effect of line
      and the linear, quadratic, and cubic effects of age. Variance components were
      estimated using a DFREML algorithm. Boars of the TS and C line did not differ in
      body weight (P > .05) in Generation 8. In Generation 9, boars of line TS were
      heavier between 118 and 198 d of age (P < .001); thereafter, body weights of the
      lines were similar (P > .05). The increase in organ weights for the testes and
      epididymides between 70 and 160 d of age were greater (P < .01) for boars of line
      TS in each generation, and differences between the lines in testis weights
      established around puberty were maintained at 450 d of age. Daily sperm
      production and CAUDASP increased more rapidly at younger ages and plateaued at
      greater values (P < .05) in boars of line TS. At ages less than 200 d, boars of
      line TS produced more sperm per gram of parenchyma than control boars.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8567451
TI  - Growth of testes and testicular morphology after eight generations of selection
      for increased predicted weight of testes at 150 days of age in boars.
AB  - Weights of testes and epididymides, body weight, and morphometric measurements of
      testicular tissue of 75 boars of a line selected for eight generations for
      predicted weight of testes at 150 d of age and 75 boars of a randomly selected
      control line were used to evaluate the effects of selection on testicular
      development at 70, 100, 130, 160, and 450 d of age (n = 15 boars per line per
      age). Body weights for boars of the select and control line did not differ (P <
      .05) and the shape of the body growth curve was similar for both lines. Boars of
      the select line had larger testes than control boars at each age (P < .05), but
      there was a significant line x age interaction. The percentage increase of the
      select line mean over the control mean for weight of testes was 37% at 70 d, a
      maximum of 120% at 100 d, and 25% at 450 d. The percentage of the testes made up
      of seminiferous tubules differed between lines (P < .01). Lines had similar means
      of approximately 28% at 70 d and 71% at 450 d, but the mean for the select line
      was larger between 100 and 160 d of age; the greatest difference was 11.6%
      (control = 43.7, select = 55.3%) at 100 d. After 70 d of age, select-line boars
      had a greater percentage of seminiferous tubules with lumens that contained
      elongated spermatids (P < .10).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567452
TI  - Genetics of the interval from weaning to estrus in first-litter sows:
      distribution of data, direct response of selection, and heritability.
AB  - A selection experiment with a selection and a control line maintained for eight
      generations was set up to study efficacy of selection for a short interval from
      weaning to estrus after weaning the first litter and to estimate genetic
      variation in the Dutch Landrace population. Intervals were recorded without
      truncation (i.e., intervals up to 234 d were observed). A mating scheme with 10
      mating groups was used to avoid inbreeding. Distribution of intervals from
      weaning to estrus was described by a mixture of a normal and an exponential
      distribution. Between lines, both underlying distributions were similar, but the
      contribution to the total distribution was different. From generation 4 onward,
      intervals were significantly shorter in the selection line than in the control
      line. Variances within lines, generations, and mating groups varied to a large
      extent. Response per unit selection differential was calculated for original data
      and three sets of transformed data, both with and without correction for unequal
      subclass numbers. Standardized responses were more precise and linear, when data
      were log-transformed, and when corrected for unequal subclass numbers. The
      assumed best estimate of the realized heritability was .17. The heritability in
      the foundation population was estimated at .36 +/- .05, using an animal model
      including all genetic relationships in the data. It was concluded that genetic
      selection decreases the average interval from weaning to estrus by reducing the
      number of sows with a record in the exponential part of the distribution.

PMID- 8567453
TI  - Technical note: changes in genetic predictions between subsequent evaluations.
AB  - A procedure was developed to compute the proportion (P) of future genetic
      predictions that would be within 1 SE of previous predictions. The procedure is
      based on the Central Limit Theorem. Whatever the distribution function, provided
      only that it has a finite variance, the sample mean will have approximately the
      normal distribution for large samples. The proportion of new individual genetic
      predictions being within 1 SE of their previous evaluation is expressed as a
      function of the change in accuracy (ACC) between the previous and subsequent
      evaluations. If little additional information is made available since the
      previous evaluation, the increase in ACC will be almost negligible. As
      anticipated the vast majority of genetic predictions will be within 1 SE of their
      previous evaluation. The proportion determined from the results of the analysis
      can be compared to P. An additional appealing feature of the procedure presented
      is the ease of implementation with most computer softwares. Finally, application
      to both simulated and field data is presented.

PMID- 8567454
TI  - Comparison of evaluation-selection systems for maximizing genetic response at the
      same level of inbreeding.
AB  - Use of improved methods of genetic evaluation and intense selection lead to
      higher rates of genetic change but also lead to higher rates of inbreeding. A
      number of methods have been proposed to attain high rates of genetic response
      with moderate or low inbreeding (i.e., restrict the number of close relatives
      selected, use false high heritability in the genetic evaluation, use assortative
      mating, adjust estimated breeding values for the relationship with those already
      selected, avoid matings of related individuals, and increase the number of
      parents selected). These various methods were compared here using stochastic
      simulation of an infinitesimal genetic model. The results were studied
      graphically plotting response against inbreeding, so allowing comparison of the
      methods at each of a range of inbreeding levels. None of the methods was best
      over all conditions. At high rates of inbreeding and with a fixed number of
      sires, several of the methods gave large decreases in inbreeding for small losses
      in response. However, these were matched by simply increasing the number of sires
      selected. There is an optimum response-inbreeding "front" attained by several
      methods, and this front seems hard to breach. Characterization of the front would
      be useful in designing selection programs.

PMID- 8567455
TI  - Influences of amount of pedigree information on computing time and of model
      assumptions on restricted maximum-likelihood estimates of population parameters
      in Swiss black-brown mountain sheep.
AB  - Average daily gain between birth and 30 d of age of 42,644 lambs of Swiss Black
      Brown Mountain Sheep were used in this analysis. The influence of amount of
      pedigree information on computing time and on REML estimates of population
      parameters was investigated on a subset of 7,848 lambs. If all available pedigree
      information was used, 89.4% of the lambs had at least four complete generations
      of known ancestors. For the reduced pedigree information, only parents and
      grandparents of a lamb were included. In the data set with complete pedigree
      information, 2,616 additional animals (without records) caused 19.4% more
      equations, 4.6 times the number of non-zero elements in the system of equations,
      and 21.2 times the computing time to reach convergence. The difference in amount
      of pedigree information had only a marginal influence on the estimates of direct
      heritability (h2), maternal heritability (m2), permanent environmental effects,
      and on the genetic correlation between direct and maternal effect (rAM). The
      complete data set of 42,644 recorded lambs was randomly split into four subsets
      to save computing time. In a fifth subset of 27,787 lambs (Set C) all
      combinations of recorded grandparents and grand-offspring were accumulated
      because they contain information on the covariance between direct and maternal
      effects (cov[AM]). Including cov(AM) in the model assumptions increased estimates
      of h2 and m2 in all subsets. Estimates from Set C were smallest but showed the
      same trend. The estimate of rAM was always strongly negative, < or = 
      .64.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567456
TI  - Genetic correlation and heritabilities for purebred and crossbred performance in
      poultry egg production traits.
AB  - Genetic correlations between purebred and crossbred performance and purebred and
      crossbred heritabilities were estimated for egg production traits of laying
      chickens using a multivariate sire model accounting for additive relationships
      between sires. Two sire lines, denoted lines 1 and 2, were crossed to one dam
      line to produce crossbred progeny. Records for egg weight, egg specific gravity,
      and egg number were collected on purebred and crossbred hens. In total, 99 sires
      in line 1 and 292 sires in line 2 were used in the analysis, each sire producing
      on average 45 purebred and 105 crossbred daughters. Estimates of purebred
      heritability in lines 1 and 2 were in range of .54 to .74 for egg number traits,
      .52 to .91 for egg weight traits, and .41 to .83 for egg specific gravity traits.
      Estimates of crossbred heritability were .04 to .51 for egg numbers, .23 to .45
      for egg weight, and .13 to .31 for egg specific gravity. The sire component in
      crossbreds differed up to 78% from the sire component in purebreds depending on
      traits. The estimate of genetic correlation (rpc) between purebred and crossbred
      performance was .56 to .73 for egg number, .69 to .99 for egg weight, and .72 to
      .82 for egg specific gravity. Although crossbred parameters were strongly
      affected by environmental factors, the results tend to agree with the theory that
      traits with a larger dominance variation and a larger difference between sire
      components in purebreds and crossbreds show a lower rpc.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8567457
TI  - Genetic and phenotypic (co)variances for production traits of intact male
      populations of purebred and composite beef cattle.
AB  - Least squares means, genetic (sigma g) and phenotypic (sigma p) standard
      deviations, and phenotypic coefficients of variation (CV) were estimated for
      growth traits of intact males from 12 breed groups combined, for nine purebreds
      combined, and for the F1, F2, F3, and F4 generations of three composite
      populations to which the nine purebreds contributed. Heritabilities (h2) and
      genetic (rg) and phenotypic (rp) correlations were estimated for growth traits,
      calving difficulty of calves with dams of different ages, and gestation length.
      Coefficients of variation and sigma g generally were similar for composites and
      contributing purebreds. Generally, estimates of h2 were similar for all breed
      groups combined, contributing purebreds combined, and composites combined.
      Estimates of h2 for calving difficulty were higher for calves with 2-yr-old dams
      than for calves with dams > or = 3 yr old and were sufficiently high (.27 and
      .31) to be a useful selection criterion for reducing calving difficulty. Mean h2
      pooled within all breed groups ranged from .35 for 200-d weight and 368-d weight
      to .48 for 368-d height. Estimates of h2 for subjective scores of anatomical
      traits were only slightly lower than those for growth and size traits. The h2 of
      scrotal circumference (.43) was similar to those for growth and size traits.
      Genetic correlations between birth weight and calving difficulty were similar for
      1) calves with dams of all ages, 2) calves with 2-yr-old dams, and 3) calves with
      dams > or = 3 yr old.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567458
TI  - Genetic and phenotypic (co)variances for production traits of female populations
      of purebred and composite beef cattle.
AB  - Least squares means, genetic and phenotypic standard deviations, and phenotypic
      coefficients of variation were estimated for growth, size, condition score, age
      at puberty, gestation length, and calving difficulty as traits of individual
      females from 12 breed groups combined, for nine purebreds combined, and for the
      F1, F2, and F3 generations of three composite populations to which the nine
      purebreds contributed. Heritabilities and genetic and phenotypic correlations
      were estimated for growth and size traits, age at puberty, gestation length, and
      calving difficulty of calves with dams of different ages. Coefficients of
      variation and genetic standard deviations were similar for composites and
      contributing purebreds for the traits evaluated. Generally, estimates of
      heritability were similar for all breed groups combined, contributing purebreds
      combined, and composites combined. Estimates of heritability for calving
      difficulty were higher for calves with 2-yr-old dams than for calves with dams >
      or = 3 yr old and were sufficiently high (.33 and .26) to be a useful selection
      criterion for reducing calving difficulty. Estimate of heritability for age at
      puberty was .31 and for gestation length was .45. The rg between birth weight and
      calving difficulty score was higher for calves with 2-yr-old dams (.59) than for
      calves with dams > or = 3 yr old (.44). The higher genetic correlation between
      birth weight and calving difficulty score (.59) in calves with 2-yr-old dams than
      between birth weight and 368-d weight (.33) suggests opportunity to reduce
      calving difficulty by reducing birth weight while maintaining 368-d
      weight.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567459
TI  - Uterine mass and uterine blood volume in mice selected 21 generations for
      alternative criteria to increase litter size.
AB  - Lines of mice, selected for 21 generations using alternative criteria to increase
      litter size, were evaluated for uterine mass and uterine blood volume to help
      explain differences in uterine capacity. For this study, mice were sampled from
      Generation 27, the sixth generation after relaxation of selection. Mice came from
      all four criteria of selection (LS = selection on number born to unaltered
      females; IX = selection on index of ovulation rate and ova success; UT =
      selection on uterine capacity; and LC = unselected control) in each of three
      replicates (a total of 12 lines). Measurement was at one of two stages, either 3
      d or 6 d of gestation. Matings were at 10 wk of age, and a total of 508 mice (17
      to 26 per line-day of pregnancy subclass) were measured. The mean of the three
      selected groups exceeded the control in uterine mass (P < .001), uterine blood
      volume (P < .002), uterine mass/body mass (P < .03), and uterine blood
      volume/body mass (P < .04) but not in uterine blood volume/uterine mass. Greater
      uterine mass and concomitantly greater uterine blood volume may have been partly
      responsible for greater uterine capacity resulting from LS, IX, and UT
      selections.

PMID- 8567460
TI  - Individual differences in docility in Limousin cattle.
AB  - Docility tests were performed over 3 yr on 906 Limousin heifers sired by 34
      males. The heifers were tested individually when they were 10 to 11 mo old in a
      pen with a handler who had 2 min to lead the animal to a corner, keep it there
      for 30 consecutive seconds, and then to stroke it. Behaviours of the animals were
      recorded and scores calculated. The first score (docility score) was a continuous
      variable combining the greatest possible information. The second score (docility
      criterion) was a categorical trait with four classes. Tests were performed by
      seven different handlers. The effects of handler, year, birth period, dam parity,
      birth region, husbandry system, and sire were estimated. Handlers, birth period,
      husbandry system, and sire had significant effects. In particular, animals that
      were managed indoors were more docile than those reared out-of-doors at least
      part of the time. Heritability estimates of the docility score (.22) and docility
      criterion (.18) seem sufficient to select for docility traits.

PMID- 8567461
TI  - Alteration of heat production in young calves in relation to posture.
AB  - The effects of feeding level and ambient temperature on time-related alterations
      of heat production in relation to physical activity (posture) were studied in
      young calves after transportation. Twenty-four 6-d-old Holstein-Friesian male
      calves were assigned in a 2 x 2 factorial design to one of two feeding levels
      (high or low) and one of two ambient temperatures (7.5 degrees C or 19 degrees
      C). Heat production was measured per calf continuously every 9 min by indirect
      calorimetry for a 2-wk period. Calf's posture during these 9-min periods was
      measured with a photoelectric cell. After arrival, heat production of calves
      decreased with time (days). The amount of decline in heat production depended on
      feeding level and ambient temperature. This decline with time was largest at the
      low feeding level at 19 degrees C. Six to 12 d after arrival, heat production
      reached steady-state levels. A steady-state level of heat production was reached
      first at the high feeding level at 19 degrees C. Averaged over treatments, heat
      production during standing was 132 kJ.kg-.75.d-1 higher than during lying. Time
      spent standing by calves increased over time. This indicated that alteration in
      time spent standing did not account for the time-related changes in heat
      production. On the contrary, physical activity (posture) partly masked the
      alterations in metabolic rate of calves after arrival. However, differences in
      physical activity (posture) accounted for differences in both time to reach
      steady-state levels and linear decline in heat production over time between
      treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567462
TI  - Effects of bovine somatotropin and insulin on whole-body and hindlimb glucose
      metabolism in growing steers.
AB  - Six Holstein steers (245 kg initial BW) were surgically prepared with chronic
      catheters to allow measurement of blood flow and nutrient flux across the
      hindlimb. Steers were used in a single-reversal design with 16-d treatment
      periods of daily i.m. injection of either excipient (control) or recombinantly
      derived bovine somatotropin (120 micrograms/kg BW). On d 15 of each period, whole
      body and hindlimb glucose metabolism were studied during a primed continuous
      infusion of [6(-3)H]glucose, under both basal conditions and during a
      hyperinsulinemic/euglycemic clamp. Somatotropin increased (P < .01) basal blood
      glucose and serum insulin by 7 and 150% respectively, with no change in glucose
      irreversible loss rate (ILR). There was no effect of somatotropin on hindlimb
      blood flow or oxygen consumption. In contrast, hindlimb lactate uptake (P < .02)
      and the ratio of glucose to oxygen uptake (P < .08) were reduced by somatotropin.
      Insulin infusion stimulated (P < .01) glucose ILR and inhibited (P < .02)
      endogenous glucose production to a lesser extent during somatotropin treatment.
      Basal plasma nonesterified fatty acid concentrations were increased (P < .01)
      during somatotropin treatment and decreased (P < .02) during insulin infusion.
      Insulin infusion increased hindlimb blood flow and glucose uptake to similar
      extents during both treatment periods. These data demonstrate that somatotropin
      treatment of growing steers decreases response of tissues to insulin (sensitivity
      in muscle, sensitivity, and responsiveness in liver and adipose tissue), thereby
      increasing glucose availability to other tissues.

PMID- 8567463
TI  - Comparison between 3-methylhistidine production and proteinase activity as
      measures of skeletal muscle breakdown in protein-deficient growing barrows.
AB  - This experiment was conducted to determine the relationship between 3
      methylhistidine (3MH) production and proteinase activity in skeletal muscles of
      growing barrows. Barrows at 13 wk of age were randomly assigned to either control
      diet available on an ad libitum basis (21% of ME consisted of protein; control
      group), control diet fed restricted (pair-fed with barrows in protein-free group;
      intake-restricted group), or protein-free diet available on an ad libitum basis
      (protein-free group) for 14 d. During the last 3 d, blood samples were collected
      for determination of 3MH production rate, which is a measure of myofibrillar
      protein breakdown. At slaughter, two muscles were taken: masseter (M) and
      longissimus (L) muscles. The muscle samples were analyzed for calpastatin, mu
      calpain, m-calpain, multicatalytic proteinase (MCP), cathepsin B, cathepsins B+L,
      and cystatins activities. Both muscles were also analyzed for amounts of DNA,
      RNA, total protein, and myofibrillar and sarcoplasmic proteins. Growth rate
      (kilograms/day) was influenced by dietary treatments (P < .05). Fractional
      breakdown rate (FBR, percentage/day) of skeletal muscle, as calculated from 3MH
      production rate (micromoles.kilogram-1.day-1), was 27% higher for the protein
      free group than for the control group. However, no differences in proteinase
      activities were observed, except for lower MCP activity in the M muscle of the
      protein-free group than in that of the other groups (P < .05). In the present
      study, no direct relation was observed between myofibrillar protein degradation
      rate and proteinase activities in skeletal muscle during a protein-free feeding
      strategy.

PMID- 8567464
TI  - Effects of porcine somatotropin administration on porcine muscles located within
      different regions of the body.
AB  - This research was conducted to evaluate the characteristics of muscle fiber
      growth and the effects of porcine somatotropin (pST; 100 micrograms.kg-1 BW.d-1)
      administration on the morphology of 12 muscles located in different regions of
      the body in barrows growing from 20 to 90 kg BW. In the course of the growth of
      control pigs, the percentage distribution of beta R fibers did not show any
      changes in all 12 muscles, whereas the percentage of alpha R and alpha W fibers
      changed in different patterns in different muscles. The administration of pST had
      no effect on fiber type distribution. The cross-sectional area of alpha W fibers
      was the largest of the three fiber types, and beta R and alpha R fibers were of
      similar size in all muscles. All fiber types in all muscles increased in cross
      sectional area by an average of 120% from 20 to 60 kg BW. After 60 kg BW, the
      growth of alpha W fibers in seven (early maturing) muscles and alpha R fibers in
      one muscle out of the 12 muscles was not apparent. The increase of their cross
      sectional area was an average of 12%, but the area of the other muscle fibers
      continued to increase by an average of 38% until 90 kg BW. The administration of
      pST increased the area of alpha W fibers in four out of seven of these early
      maturing muscles by an average of 25%, suggesting some possible relationships
      between pST effects and the rate of muscle fiber maturation. Most of the muscles
      that responded to pST treatment were located in hindlimb region.

PMID- 8567465
TI  - Dietary vitamin E supplementation shifted weight loss from drip to cooking loss
      in fresh beef longissimus during display.
AB  - Effects of dietary vitamin E supplementation on drip loss, cooking loss, and
      muscle fiber disruption in fresh beef loin steaks from Holstein and crossbred
      beef steers were studied. Nine Holstein steers and nine beef steers were fed a
      control diet and nine Holstein steers and eight beef steers were supplemented
      daily with 298 IU of vitamin E/kg of diet for 211, 232, or 252 d. Drip loss,
      cooking loss, cooking yield, and shear value were measured in each longissimus
      lumborum sample displayed in PVC film for 2, 6, 10, or 14 d. Dietary vitamin E
      supplementation produced meat that had smaller (P < .001) increases in drip loss
      during 14 d of display but higher (P < .01) cooking losses. Cooking yield was
      reduced (P < .05) by vitamin E supplementation. Vitamin E supplementation reduced
      (P < .01) muscle cell disruption in beef steak displayed for 14 d. These results
      indicated that dietary vitamin E treatment stabilized cell integrity and enhanced
      the ability of beef steak to hold sarcoplasmic components during display,
      although subsequent losses due to cooking were greater.

PMID- 8567466
TI  - Effects of restraint and isolation stress and epidural blockade on endocrine and
      blood metabolite status, muscle glycogen metabolism, and incidence of dark
      cutting longissimus muscle of sheep.
AB  - Crossbred lambs (47.3 kg BW) were used to study the effects of restraint and
      isolation stress on endocrine status and blood metabolites, antemortem
      glycogenolysis, and incidence of the dark-cutting condition (DCC) in the
      longissimus muscle (LM) and to determine the role of muscle contraction in the
      formation of the DCC in sheep. Lambs were assigned randomly to three treatments:
      unstressed controls (C); a single 6-h period of restraint and isolation stress
      (RIS); and a single 6-h period of RIS following epidural blockade (RISEB) with
      lidocaine. Blood was collected immediately before lambs were subjected to RIS and
      RISEB and at 12-min intervals during the 6-h period. Serum concentrations of
      glucose, lactate, and insulin were higher (P < .01) in RIS and RISEB lambs than
      in C lambs. Serum free fatty acid concentrations were higher (P < .01) in
      stressed lambs only during the first 4 h of stress. Plasma epinephrine and
      cortisol concentrations also were higher (P < .01) in RIS and RISEB lambs than in
      C lambs. Lambs were slaughtered within 30 min after completion of stress.
      Immediately after stunning and at .75, 3, 6, 12, and 24 h postmortem, samples
      were removed from the LM in the hindsaddle and foresaddle for glycogen, lactate,
      and pH determinations. Muscle pH was elevated (P < .01) by RIS and RISEB;
      ultimate pH exceeded 6.0. The LM from carcasses of RIS and RISEB lambs had lower
      (P < .01) glycogen and lactate concentrations in both regions than the LM of C
      lambs. Subjecting sheep to a single 6-h period of RIS was an effective animal
      model to induce the DCC. Failure of the epidural blockade to inhibit antemortem
      glycogen metabolism and formation of the DCC indicates that muscle contraction
      was not requisite to those processes in sheep.

PMID- 8567467
TI  - Retail consumer acceptance of beef tenderized with calcium chloride.
AB  - Beef inside round subprimals were injected with a 200 mM calcium chloride (CaCl2)
      solution at 5% (wt/wt) to determine its effects on beef steak palatability and
      quality traits. Alternating subprimals from the right and left sides were
      selected for injection of CaCl2 or not injected to serve as a control. After 7 d
      of postmortem storage, 2.5-cm-thick steaks were cut from each subprimal for
      consumer evaluation (n = 478) in a retail setting. Three supermarkets with
      customers varying widely in income were selected as test sites for measuring
      consumer perceptions of the treated and control steaks and package labeling
      acceptance. Supermarket, income level, education, and sex were evaluated for
      their impact on acceptance of calcium-injected beef. Steak flavor and tenderness
      both were important in determining beef eating quality; 50% of consumers said
      tenderness was the most important and 40% said flavor was the most important.
      Consumers visually preferred CaCl2-treated steaks 71% of the time over the
      control steaks based on package labeling. The CaCl2 injection improved
      tenderness, juiciness, flavor desirability, and overall palatability ratings by
      the consumers for inside round steaks and did not cause any off-flavor problems
      compared with the controls. Therefore, injecting beef with a solution of 200 mM
      CaCl2 at 5% (wt/wt) can improve retail consumer evaluations of beef steak
      tenderness and reduce tenderness variation without detrimental effects on other
      palatability or quality traits.

PMID- 8567468
TI  - Valine requirement of the finishing pig.
AB  - Pigs weighing approximately 70 kg were used in two experiments to determine the
      valine requirement during the finishing period. In the first experiment, 10 gilts
      were allotted in two 5 x 5 Latin square designs to five semipurified diets that
      ranged in valine concentration from .35 to .55%. Urinary urea excretion was
      measured during each of the 3-d periods of the Latin square. Urea N excretion in
      relation to N intake and to creatinine N excretion was minimized (quadratic
      effect, P < .10) at valine concentrations of .45 to .50%. In Exp. 2, 36 barrows
      and 36 gilts were fed one of six diets containing .35 to .60% valine. The highest
      weight gains (not significant) and feed efficiencies (quadratic effect, P < .05)
      were achieved by the pigs that consumed .45% valine. Plasma urea concentration at
      the end of the experiment was lowest (quadratic effect, P < .05) in pigs that
      consumed .50% valine. Estimates of the valine requirement based on breakpoint and
      quadratic equation analyses ranged from .40 to .50% total valine (.33 to .43%
      ileal digestible valine). Pigs in Exp. 2 consumed approximately 2.5 kg/d (8,850
      kcal/d of ME). Thus, the estimate of the valine requirement is approximately 11
      g/d. These estimates of the valine requirements of finishing pigs are slightly
      higher than the National Research Council requirements when expressed as a
      percentage of the diet but are similar when expressed on a grams per day basis.

PMID- 8567469
TI  - Estimation by regression analysis of endogenous amino acid levels in digesta
      collected from the distal ileum of pigs.
AB  - An experiment was conducted to estimate by simple linear regression the levels of
      endogenous amino acids in digesta collected from the distal ileum in pigs. Six
      barrows, average initial BW 35 kg, were fitted with a simple T-cannula at the
      distal ileum and fed six diets according to a 6 x 6 Latin square design. Six
      cornstarch-based diets containing six levels of CP from soybean meal (4, 8, 12,
      16, 20, and 24% CP, respectively) were formulated. Chromic oxide (.4%) was
      included as the digestibility marker. Each experimental period consisted of 8 d.
      Ileal digesta were collected, at 2-h intervals, for a total of 24 h during d 7
      and 8. There were linear relationships (P < .001) between dietary contents of
      apparent ileal digestible and total amino acids, irrespective of the ranges in
      graded dietary levels of amino acids. Determined with the regression technique,
      the endogenous levels of the indispensable amino acids (grams/kilogram of DMI)
      were as follows: arginine, .64; histidine, .23; isoleucine, .46; leucine, .69;
      lysine, .47; methionine, .13; phenylalanine, .31; threonine, .69; and valine,
      .54. Differences in the ranges of graded dietary levels of amino acids resulted
      in large differences in the estimated amounts of endogenous amino acids in ileal
      digesta. Furthermore, it seems that the levels of endogenous amino acids, as
      grams/kilogram of DMI, were constant at different dietary levels of amino acids,
      whereas the contributions of endogenous amino acids, as percentages of their
      dietary contents, decreased curvilinearly with increasing dietary contents.
      Therefore, apparent ileal digestibilities of amino acids were quadratically
      related to their dietary contents until plateau digestibilities were reached,
      whereas the true ileal digestibilities of amino acids were independent of their
      respective dietary contents. Furthermore, true ileal amino acid digestibilities
      should be determined from their corresponding plateau apparent ileal
      digestibilities. In conclusion, the levels of endogenous amino acids in ileal
      digesta can be determined reliably from the linear relationships between dietary
      contents of apparent ileal digestible and total amino acids. An important
      methodological consideration in the determination of endogenous amino acids by
      regression analysis is to design an appropriate range of graded dietary levels of
      amino acids.

PMID- 8567470
TI  - Dietary fiber for cats: in vitro fermentation of selected fiber sources by cat
      fecal inoculum and in vivo utilization of diets containing selected fiber sources
      and their blends.
AB  - Two experiments were conducted to evaluate the addition of single sources and
      blends of dietary fibers to cat diets. In Exp. 1, fermentability of selected
      fibrous substrates by cat fecal microflora was evaluated. After 24 h of
      fermentation, OM disappearance (OMD) and total short-chain fatty acid (SCFA)
      production were greatest (P < .05) for citrus pectin, guar gum, and locust bean
      gum, whereas Solka Floc resulted in the least (P < .05) OMD and total SCFA
      production. In Exp. 2, six diets were formulated based on results of Exp. 1. The
      highest (P < .05) digestibilities of DM and OM occurred when cats consumed the
      diet with no supplemental fiber, and the lowest (P < .05) digestibilities
      occurred when cats consumed the SCFA blend (SC) diet. Nitrogen and lipid
      digestibilities also were lowest (P < .05) for cats consuming the SC diet,
      whereas total dietary fiber (TDF) digestibility (P < .05) was greatest for cats
      consuming the beet pulp, SC, and combination blend diets. Fecal consistency
      scores were highest (P < .05) for cats consuming the SC diet, indicating liquid,
      unformed stools. In conclusion, the in vitro fermentation technique was
      reasonably accurate in predicting in vivo digestion of fiber. The SC diet, which
      contained the most fermentable fibers, severely decreased nutrient digestibility
      and resulted in poor stool characteristics. Diets that contain moderately
      fermentable fiber provide fermentation end products that may be important in
      maintaining the health of the gastrointestinal tract of the cat.

PMID- 8567471
TI  - Effects of spray-dried porcine plasma protein on growth traits and nitrogen and
      energy balance in mice.
AB  - Energy and nitrogen balances of mice receiving a dried skim milk-based control
      diet were compared to a similar group of mice receiving a diet containing 8%
      spray-dried plasma protein (SDPP). Mice were housed in pairs in metabolism cages
      with feed and water available for ad libitum intake. Five cages were assigned to
      each diet for a 21-d feeding period. Mice fed SDPP gained more weight (P < .01),
      consumed more feed (P < .01), and had higher gain: feed ratios (G:F) (P < .01)
      than mice fed the control diet during wk 1. No significant differences in growth,
      feed intake, or G:F were detected during wk 2. During wk 3, mice receiving the
      control diet tended to gain more (P < .10) and had a higher G:F (P < .01).
      Nitrogen intake and retention were greater for mice fed SDPP (P < .02). Energy
      intake was greater for mice fed SDPP (P < .01); however, energy retention was not
      different between treatment groups due to greater (P < .01) metabolic energy
      losses (urinary energy+heat production). Empty gut weight was greater for control
      mice on an absolute basis (P < .05) and when expressed as a percentage of BW (P <
      .02). Liver weights of mice fed SDPP were greater on an absolute basis (P < .02)
      and as a percentage of BW (P < .01). Feed intake, growth rate, and G:F were
      increased by dietary addition of SDPP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567472
TI  - Effect of weaning diet on the ecology of adherent lactobacilli in the
      gastrointestinal tract of the pig.
AB  - Sixteen pigs were included in an investigation of the effects of weaning and
      weaning diet on the ecology of adherent Lactobacillus species in the
      gastrointestinal tract. At 28 d of age four pigs were killed and were designated
      as the preweaning control (PW). Four pigs remained on the sow (Sow), four pigs
      were fed a corn-soy-lactose (CSL) diet, and the remaining four pigs were fed a
      corn-soy (CS) diet. Pigs from the latter three treatments were killed at 38 d of
      age. Tissue samples were taken from the pars esophagus, ileum, and cecum and the
      adherent lactobacilli were enumerated using Rogosa SL agar. Bacterial colonies
      were randomly selected from Rogosa SL agar plates and speciated using cell type,
      morphology, and substrate fermentation tests. The species data were used to
      calculate the Shannon, Simpson, and evenness diversity indices. Shannon and
      Simpson diversity index values when averaged across tissues were lower (P < .05)
      for PW than for postweaning treatments (Sow, CSL, and CS) and lower (P < .05)
      when pigs receiving sow's milk (PW and Sow) were compared with pigs receiving the
      dry diets (CSL and CS). The diversity of adherent Lactobacillus is altered by the
      form of the diet fed to weanling pigs, and statistical ecological methods provide
      a powerful way of analyzing the ecology of the gastrointestinal tract.

PMID- 8567473
TI  - Protein and lipid accretion in body components of growing gilts (20 to 45
      kilograms) as affected by energy intake.
AB  - Twenty-eight commercial hybrid gilts with a high genetic capacity for lean gain
      were used to determine the relationships between energy intake and tissue
      deposition and body composition between 20 and 45 kg BW. Four pigs were killed at
      20 kg to determine body composition at the beginning of the experiment. The other
      24 gilts received one of six intake levels (1.7, 2.2, 2.7, 3.2, and 3.7 times
      maintenance [M], and ad libitum) ranging from 11.3 to 27.2 MJ of DE/d. At 45 kg
      BW, the gilts were killed and dissected into carcass and organ fractions.
      Carcasses of pigs at 2.2 and 3.7 x M were dissected into lean and other carcass
      parts. Daily gain increased linearly (P < .001) from 371 to 1,075 g/d. Gain/feed
      increased (P < .01) from 500 to 600 g/kg. Deposition rates of protein and lipid
      increased linearly (P < .001) from 75 to 172 g/d and from 28 to 193 g/d,
      respectively. The ratio between lipid and protein deposition increased (P < .001)
      from .3 to 1.1. The relative organ mass increased (P < .001) with increasing
      energy intake, whereas the body lean percentage decreased (P < .01) from 53.9% at
      2.2 x M to 47.4% at 3.7 x M. In the carcass and organs, protein content decreased
      (P < .01) and lipid content increased (P < .001) with increasing energy intake.
      Protein deposition increased with 5.77 g/MJ increase in DE intake, of which only
      approximately 40% was deposited in the lean tissue.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8567474
TI  - Determination of apparent ileal amino acid digestibility in barley and canola
      meal for pigs with the direct, difference, and regression methods.
AB  - Three methods were evaluated for the determination of apparent ileal
      digestibility values of amino acids in feedstuffs with a low protein (barley,
      10.2% CP) and a high protein content (canola meal, 38.2% CP). Five barrows,
      average initial BW 40 kg, were fitted with a simple T-cannula at the distal ileum
      and fed five diets according to a 5 x 5 Latin square design. Diet 1 contained
      42.7% canola meal providing the sole source of dietary amino acids. Diets 2, 3,
      and 4 contained three graded levels of barley (22.5, 45.0, and 67.5%,
      respectively) and three graded levels of canola meal (36.6, 30.5, and 24.4%,
      respectively). Diet 5 contained 90.0% barley, which provided the sole source of
      dietary amino acids. With the exception of diet 5, the diets were formulated to
      contain 16% CP. Chromic oxide (.4%) was included as the digestibility marker. The
      pigs were fed twice daily, equal amounts, at 0800 and 2000. The dietary allowance
      was 1,800 g/d. Each experimental period comprised 8 d. Ileal digesta were
      collected for a total of 24 h during d 7 and 8 at 2-h intervals. Apparent ileal
      digestibility values of amino acids in barley were determined with the direct
      method from diet 5, with the difference method from diets 2, 3, and 4, and with
      the regression method from diets 1, 2, 3, and 4. Digestibility values of amino
      acids in canola meal were determined with the direct method from diet 1, with the
      difference method from diets 2, 3, and 4, and with the regression method from
      diets 1, 2, 3, and 4. There were no differences (P < .05) in the digestibility
      values in barley between the difference method when barley was included at 67.5%
      in the diet and the regression method. However, the digestibility values were
      lower (P < .05 or < .10) when these were determined with the direct method. There
      were no differences (P > .05) in the digestibility values of canola meal when
      these were determined with the direct method, the difference method, when canola
      meal was included at 36.6% in the diet, and the regression method. In conclusion,
      amino acid digestibility values in feedstuffs with a low protein content should
      be determined with the difference or regression methods rather than with the
      direct method. Amino acid digestibility values in feedstuffs with a high protein
      content can be determined with either method.

PMID- 8567475
TI  - Toxicity and growth-promoting potential of spermine when fed to chicks.
AB  - Previous studies have shown that the feeding of putrescine, a biogenic amine and
      the precursor of the mammalian polyamines, can promote whole-body growth of
      chicks. The current study was undertaken to determine the effect of spermine,
      also a biogenic amine and the most cationic of the polyamines, under similar
      conditions. In Exp. 1, 120 week-old chicks were fed purified crystalline amino
      acid-based diets containing 0, .2, .4, .6, .8, or 1.0% spermine for 14 d.
      Spermine proved highly toxic and growth rates were reduced compared with controls
      when even .2% was fed. In Exp. 2, chicks were fed 0, .0375, .0750, or .1000%
      spermine. These concentrations proved less toxic than those used in Exp. 1.
      Supplemental dietary cysteine was then provided at 0, .3, .6, and .9% together
      with 0, .025, .050, or .400% spermine (Exp. 3) because depletion of cellular
      glutathione has been suggested as contributing to spermine's toxicity. Even high
      levels of cysteine supplementation did not overcome spermine's toxicity.
      Subsequent dietary provision of L-2-oxothiazolidine-4-carboxylic acid (OTC, Exp.
      4), a cysteine prodrug, showed that depletion of cellular glutathione was not
      likely a cause of spermine toxicosis. A trend toward increased weight gain and
      feed efficiency was observed when low concentrations of spermine were fed. It was
      concluded, however, that dietary spermine was more toxic to chicks than was
      previously seen for putrescine, that any growth-promoting effects of dietary
      spermine are small, and that supplements of dietary cysteine or OTC are unlikely
      to increase these effects by overcoming spermine toxicosis.

PMID- 8567476
TI  - Immunization of heifers against gonadotropin-releasing hormone: antibody titers,
      ovarian function, body growth, and carcass characteristics.
AB  - To investigate the effects of active immunization of cyclic beef heifers with
      different doses of a human serum albumin-Cys-Gly-GnRH (HSA-GnRH) conjugate on
      antibody titers, ovarian function, body growth, and carcass characteristics, 32
      heifers (BW = 477 +/- 7.1 kg; mean +/- SE) were assigned to one of four
      immunization treatments: .1 mg of HSA or .01, .1, or 1.0 mg of HSA-GnRH,
      respectively. All heifers received a primary (d 0) and booster (d 28)
      immunization using DEAE-dextran as adjuvant. The duration of the experiment was
      158 d. Overall antibody titers against GnRH were greater (P < .05) for heifers
      immunized against GnRH (13 +/- 3.3, 22 +/- 3.8, and 19 +/- 2.8% binding at a
      plasma dilution of 1: 640 for Treatments 2 to 4, respectively) than for controls
      (1 +/- .1%). The numbers of heifers that became anestrous (plasma progesterone <
      .5 ng/mL for > 21 d) were 1/8, 8/8, 7/8, and 8/8, respectively. The interval from
      primary immunization to anestrus (40.7 +/- 6 d) and the duration of anestrus (78
      +/- 7 d) were not affected by dose of HSA-GnRH conjugate. The number of
      ovulations detected was reduced (P < .05) in GnRH-immunized (4.6 +/- .64, 4.0 +/-
      .70, and 3.6 +/- .60 for Treatments 2 to 4, respectively) compared with control
      heifers (9.4 +/- .20). During induced anestrus, follicular growth was generally
      arrested (< 5 mm in diameter) and plasma estradiol decreased.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8567477
TI  - Effects of growth rate on carcass composition and lipid partitioning at puberty
      and growth hormone, insulin-like growth factor I, insulin, and metabolites before
      puberty in beef heifers.
AB  - The effect of three rates of gain on carcass composition, lipid partitioning, age
      and BW at puberty, and concentrations of growth hormone (GH), IGF-I, insulin,
      glucose, and NEFA in plasma were evaluated in 38 Angus x Hereford heifers.
      Heifers were allotted by BW and age to three treatments with a replication in
      each of 2 yr: full-fed (n = 13; FF) to gain 1.36 kg/d; limit-fed (n = 12; LF) to
      gain .68 kg/d; maintenance-full-fed (n = 13; MFF) to gain .23 kg/d for 16 wk,
      then full-fed to gain 1.36 kg/d. Heifers were slaughtered within 10 d after the
      onset of puberty. At slaughter, kidney, pelvic, and heart fat (KPH) and udder
      (UDDER) were separated from carcass, as was fat surrounding viscera (OM). After
      48 h at 4 degrees C a carcass side was dissected into subcutaneous fat (SC),
      intermuscular fat (SEAM), soft tissue (SFT = inseparable lean and fat), LEAN, and
      BONE. In yr 1, LF heifers (431 d) were older (P < .05) than MFF heifers (371 d)
      at puberty, but age of FF heifers (389 d) did not differ (P > .10) from that of
      LF and MFF heifers. In yr 2, FF heifers (351 d) were younger (P < .05) than LF
      and MFF heifers (398 and 434 d, respectively). The FF heifers had greater (P <
      .05) BW and a greater (P < .01) percentage of lipid in the carcass at puberty
      than LF and MFF heifers. During the first 16 wk of treatment, concentrations of
      NEFA were greater in heifers with slower daily gains (MFF > LF > FF; P < .01).
      Concentrations of NEFA were lesser and concentrations of IGF-I and insulin were
      greater in plasma of FF than in that of MFF heifers during the 10 wk before
      puberty. Treatment significantly altered age, BW, carcass composition, and lipid
      partitioning at puberty in beef heifers. We conclude that the percentage of body
      fat is not the sole regulator of puberty, and age may be an important modulator
      in determining the onset of puberty in beef heifers.

PMID- 8567478
TI  - Effects of single or primary plus booster prostaglandin F2 alpha immunization
      regimens on immune, ovarian, and growth responses of heifers.
AB  - Growth rate of heifers is reduced by prostaglandin F2 alpha (PGF) immunization
      following a primary and booster regimen. The objective was to attenuate the
      immune response with or without a booster immunization; specifically, the effects
      of booster interval, dose of PGF-human serum albumin (HSA) conjugate at booster,
      adjuvant type, or single immunization with one or two adjuvants were examined.
      Three experiments were conducted using 175 cyclic heifers. Plasma PGF antibody
      titers were measured every 2 wk and progesterone concentrations every 3 to 4 d.
      In Exp. 1, single immunization with one adjuvant (3.3 mg of PGF-HSA in either
      DEAE-dextran [DEAE] or non-ulcerative Freund's adjuvant [NUFA]; or 10.0 mg of PGF
      HSA in NUFA) did not induce sufficient antibody titers to consistently induce
      persistent corpora lutea (CL). Booster intervals of either 14, 21, or 28 d
      increased titers sufficiently to induce persistent CL (34/35 heifers), but ADG of
      heifers was less (P < .05) than for those given a single immunization. In Exp. 2,
      1.0 mg of conjugate for booster immunization induced a greater (P < .05) immune
      response than 3.3 mg, and both doses decreased (P < .05) ADG. Single
      immunization, with half the conjugate dose in DEAE and half in NUFA injected
      separately, induced persistent CL in 7/8 heifers without decreasing ADG compared
      with controls. In Exp. 3, single immunization, with half the conjugate dose in
      DEAE and half in NUFA injected separately, prolonged (P < .05) the intervals to
      peak titer compared with the booster treatment, but the incidence (13/15 vs 8/8)
      and duration (120 +/- 4.8 vs 111 +/- 7.9 d) of persistent CL were similar, and
      ADG was greater (P < .05). In conclusion, attempts to attenuate the immune
      response following booster immunization were unsuccessful. Single immunization,
      using two adjuvants separately, induced persistent CL for at least 120 d without
      decreasing ADG compared with the primary and booster regimen.

PMID- 8567479
TI  - Effects of fill volume of diets on digestive tract kinetics and fattening pattern
      of growing Holstein-Friesian bull calves.
AB  - Young Holstein-Friesian bull calves were tested in three trials for their
      performance and digestive tract kinetic responses to diets differing in their
      fill volume (FV) in the digestive tract. In Trial 1, a high ME (11.7 MJ/kg of DM)
      diet was compared with three medium ME (10.5 MJ/kg of DM) diets, one of high FV
      and two of low FV. In Trial 2, two silages (wheat and sorghum), differing in FV,
      were compared with or without poultry litter inclusion. All the diets in this
      trial had the same ME content of 10.5 MJ/kg of DM. Rate of gain, DM and ME
      intake, and depot fat percentage at slaughter were recorded. In Trial 3, two
      diets (high and low FV) and the same ME content of 10.4 MJ/kg of DM were compared
      in a short-term trial for digestive tract kinetics using a single dose of Cr-NDF
      and Co-EDTA as particulate and solute markers, respectively. Calves in Trial 1
      fed medium ME and low FV diets had higher (not significant) DMI than high ME
      calves but similar ADG, whereas medium ME and high FV calves had the lowest DMI
      (P < .1) and ADG (P < .05). Low FV and medium ME calves were leaner (P < .05) at
      slaughter than the high ME calves and fatter (not significant) than the high FV
      and medium ME calves. In Trial 2, reduction of FV by silage replacement increased
      DMI (P < .01) and ADG (P < .05). Incorporation of poultry litter into the diets
      resulted in effects in the same direction (not significant). Such a reduction
      caused increased (P < .01 for both silage end poultry litter effects) deposition
      of cod fat in the carcass. Mean retention time estimations in Trial 3 indicated
      increased (P = .055) particle retention time in the low FV calves, compared to
      the high FV calves. This increase was due to a longer (P = .1) stay of particles
      in the lower parts of the digestive tract, and not in the rumen. Lowering the FV
      of medium ME diets increased DMI of calves to support ADG equal to that of a high
      ME diet, but with a lower fat accumulation.

PMID- 8567480
TI  - Influence of altering ruminal degradation of soybean meal protein on in situ
      ruminal fiber disappearance of forages and fibrous byproducts.
AB  - The objective was to determine the effects of altering ruminal CP degradation of
      soybean meal (SBM) by roasting (Exp. 1) on ruminal characteristics and extents of
      in situ disappearance of DM, OM, and fiber components (Exp. 2). A control diet
      (8.2% CP) containing oat hulls, corn silage, starch grits, ammoniated corn cobs,
      and molasses was supplemented to 17.1% CP with unroasted SBM (SBM-0) or SBM
      roasted at 165 degrees C for 75, 150, or 210 min (SBM-75, SBM-150, and SBM-210,
      respectively). In Exp. 1, SBM was incubated for 0, 2, 4, 8, 12, 16, and 24 h in
      the rumen of two steers that were fed the SBM-0 diet. Extents of ruminal CP
      degradation and rates of N disappearance decreased (P < .05) linearly with
      increasing roasting time of SBM. In Exp. 2, five ruminally cannulated steers were
      used in a 5 x 5 Latin square design and were fed the five diets listed above
      during five 11-d periods. On d 11, five substrates (alfalfa hay, orchardgrass
      hay, corn silage, soy hulls, and wheat straw) were incubated in the rumen for 24
      h. Extents of in situ disappearance of DM, OM, and fiber (NDF, ADF, cellulose,
      hemicellulose, and total dietary fiber) were analyzed as a split-plot design. No
      substrate x diet interaction (P > .05) was observed for any of the measurements
      evaluated. Extents of in situ disappearance (24 h) of DM, OM, and fiber were
      highest (P < .05) when the control diet was fed and were lowest (P < .05) when
      the SBM-0 diet was fed. Decreasing the availability of SBM protein in the diet by
      roasting increased (P < or = .10) extents of in situ disappearance of DM, OM, and
      fiber linearly. These extents were similar for steers fed the control diet or the
      diet containing SBM-210. Ruminal concentrations of NH3 N, branched-chain VFA, and
      valerate were highest (P < .05) and ruminal pH lowest (P < .05) when the SBM-0
      diet was fed. Results indicated a rapid ruminal fermentation of both protein and
      readily available carbohydrates of SBM (resulting in pH below 6.0) during the
      first 4.5 h after feeding the SBM-0 diet. Making both protein and readily
      available carbohydrates of SBM more slowly fermentable by roasting slowed early
      fermentation processes, maintained higher ruminal pH, and encouraged earlier and
      faster ruminal fiber digestion.

PMID- 8567481
TI  - Effect of level and type of fat on subacute acidosis in cattle fed dry-rolled
      corn finishing diets.
AB  - Five experiments were conducted to determine the effect of fat addition to dry
      rolled corn (DRC) finishing diets on subacute acidosis. In Exp. 1, five ruminally
      fistulated steers (410 +/- 12 kg BW) were used in a 5 x 5 Latin square design.
      Treatments consisted of 0, 2, 4, 6, or 8% tallow added to a 50% fine-ground corn:
      50% dry-rolled wheat basal challenge diet and dosed intraruminally as an acidosis
      challenge. Area below pH 6 was determined to quantify the total decrease in
      ruminal pH over a 24-h period. Area below pH 6 responded quadratically (P < .05);
      greatest time below pH 6 occurred with diets containing 2, 4, and 6% tallow. In
      Exp. 2, six ruminally fistulated steers (527 +/- 47 kg BW) were used in a 6 x 6
      Latin square design and intraruminally dosed with 0, 4, 6, or 8% tallow or 4 or
      8% yellow grease added to a 50% fine-ground corn:50% dry-rolled wheat basal
      challenge diet. Area below pH 6 responded quadratically for both tallow (P = .10)
      and yellow grease (P < .05) and was greatest for steers dosed with 4% tallow or
      yellow grease and decreased as tallow or yellow grease increased from 4 to 8%.
      Experiment 3 was a metabolism study using six ruminally fistulated steers (469 +/
      68 kg BW) in a 6 x 6 Latin square design. Cattle were fed a DRC finishing diet
      containing 0, 4, 6, or 8% tallow or 4 or 8% yellow grease.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8567482
TI  - Plant compositional constituents affecting between-plant and animal species
      prediction of forage intake.
AB  - The purpose of the study was to identify plant compositional constituents that
      influence forage intake. Emphasis was put on the ratio in vitro digestibility of
      organic matter (IVDOM):NDF because preliminary work with cattle and a limited
      number of forages showed the ratio to account for more variation in intake than
      either IVDOM or NDF alone. The compositional constituents were tested in intake
      prediction models using local and published data (n = 302) on grass pastures,
      silages, hays, straws, legumes, grass-legume mixtures, and shrubs ingested by
      both browsing and grass-eating ruminants (goats, red deer, impala, blesbok,
      sheep, cattle, and blue wildebeest). In the local experiments, esophageally
      fistulated and fecal bag-harnessed animals were used to collect representative
      grazed forage samples from pastures and to determine OM excreted, respectively.
      Forage intake was calculated as OM excreted divided by (1-IVDOM). Intake of
      silages, hays, and straws was measured indoors in digestibility trials. Intakes
      among species were compared after scaling for size by BW raised to the power of
      .9. Major contributors to the variation in forage intake were ash, hemicellulose,
      IVDOM:NDF, ADL, and the interaction between DM content and, respectively, ash, N,
      and ADL. High tannin/phenol concentrations proved limiting to intake. The ratio
      of IVDOM:NDF accounted for 67% of the variation in forage intake if data for
      which the other constituents had an effect were omitted, and the equation, OMI,
      g.kg BW-.9.d-1 = 70-97e-.975(IVDOM:NDF), predicted intake across all forages and
      ruminant species with a Sy.x of 5.3 g.kg BW-.9.d-1 (CV = 15%). The ratio of
      IVDOM:NDF should be valuable as a relatively inexpensive and rapid method to
      screen forages and cultivars.

PMID- 8567483
TI  - Effects of forage level and canola seed supplementation on site and extent of
      digestion of organic matter, carbohydrates, and energy by steers.
AB  - The objective of this study was to determine the effects of fat supplementation
      from canola seed (CS) on ruminal fermentation and postruminal digestion of OM,
      carbohydrates, and energy of diets containing different levels of forage. Six
      ruminally and duodenally cannulated beef steers (354 kg +/- 18) were given ad
      libitum access to six isonitrogenous diets that were offered twice daily in a 6 x
      6 Latin square design. Treatments were arranged as a 2 x 3 factorial with two
      forage levels (70 vs 30% of dietary DM as corn silage) and three forms of CS
      supplementation including no CS or CS added at 10% of dietary DM as whole CS
      treated with alkaline hydrogen peroxide or untreated crushed CS. Fat from CS
      provided 5% of dietary DM. The remaining dietary ingredients were corn, canola
      meal, molasses, and urea. No interactions (P > .05) between dietary forage level
      and CS supplementation were observed for ruminal characteristics or digestion of
      OM, carbohydrates, and energy in the rumen, postruminally, or in the total tract.
      Fat supplementation from CS did not affect (P > .05) DMI. With few exceptions,
      fat supplementation did not affect (P > .05) ruminal, postruminal, or total tract
      digestibilities of OM, structural and nonstructural carbohydrates, and GE.
      Ruminal disappearance of GE was decreased (P < .05) when diets were supplemented
      with fat from whole treated CS, and total tract digestibilities of OM and GE were
      decreased (P < .05) when diets were supplemented with fat from CS in either form.
      Ruminal pH, concentrations of NH3 N and total VFA, and molar proportions of
      acetate, propionate, and butyrate were not affected (P > .05) by fat
      supplementation. Results suggest that fat supplementation from CS (at 5% of
      dietary DM) as whole treated or untreated crushed had no negative effects on
      ruminal fermentation of OM, carbohydrates, or energy when steers were given ad
      libitum access to diets containing high or low forage.

PMID- 8567484
TI  - Composition of ruminal bacteria harvested from steers as influenced by dietary
      forage level and fat supplementation.
AB  - The objective of this study was to examine the effects of dietary forage level
      and fat supplementation on the chemical composition of mixed ruminal bacteria
      (MRB). Six ruminally cannulated beef steers (354 kg +/- 18) were given ad libitum
      access to six diets (13.2% CP; DM basis) that were offered twice daily in a 6 x 6
      Latin square design. Treatments were arranged as a 2 x 3 factorial with two
      forage levels (70 vs 30% of dietary DM as corn silage) and three forms of fat
      supplementation including no canola seed or canola seed added at 10% of dietary
      DM as whole treated with alkaline hydrogen peroxide or untreated crushed. Canola
      seed contributed 5% added fat to the total diet. The remaining dietary
      ingredients were corn, canola meal, molasses, and urea. No interactions (P > .05)
      between dietary forage level and canola seed supplementation were observed.
      Concentrations of OM, N, and all amino acids were higher (P < .05) in MRB from
      steers fed low forage than in MRB from steers fed high forage. Concentrations of
      purines and GE and the N:purines ratio in MRB were not affected (P > .05) by
      dietary forage level or canola seed supplementation. Canola seed supplementation
      did not affect (P > .05) concentrations of OM, N, or most of the amino acids in
      MRB. Concentrations of four essential amino acids (i.e., isoleucine, leucine,
      lysine, and phenylalanine) in MRB were decreased (P < .05) due to canola seed
      supplementation. Dietary forage level did not affect (P > .05) concentrations of
      long-chain fatty acids in MRB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567485
TI  - Influence of nitrogen fertilization and defoliation frequency on nitrogen
      constituents and feeding value of annual ryegrass.
AB  - Two experiments were conducted to determine the seasonal effects of N fertilizer
      (NF) and defoliation interval (DI) on specific N fractions within annual ryegrass
      (AR) and overall usage of AR N by growing lambs. In Exp. 1, NF (0, 112, 224, and
      336 kg of N/ha) and DI of 2, 4, or 6 wk were factorially applied to AR plots.
      Both decreasing DI and increasing NF increased N levels in AR in a manner that
      depended on harvest date (NF or DI x harvest date interaction, P < .05). The
      proportions of .2% NaOH soluble N or soluble protein N were not affected (P >
      .05) by NF or DI. Although NF had no effect (P > .05) on in situ disappearance of
      DM, decreasing the DI seemed to reduce the severity of the season-induced
      reduction in DM disappearance (DI x harvest date interaction, P = .04). In Exp.
      2, NF (0 or 224 kg of N/ha) and a DI of 2 or 6 wk were factorially applied to AR
      plots. Fresh, frozen AR was fed in semipurified diets (48% of DM as AR) to four
      wether lambs (23 +/- 1.3 kg) using a 4 x 4 Latin square. Diets including AR had
      greater ruminal DM and plant N digestibilities when AR had a 2-wk vs a 6-wk DI
      with NF but had reduced digestibilities when AR had a 2-wk vs a 6-wk DI without
      NF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567486
TI  - Methane emissions from cattle.
AB  - Increasing atmospheric concentrations of methane have led scientists to examine
      its sources of origin. Ruminant livestock can produce 250 to 500 L of methane per
      day. This level of production results in estimates of the contribution by cattle
      to global warming that may occur in the next 50 to 100 yr to be a little less
      than 2%. Many factors influence methane emissions from cattle and include the
      following: level of feed intake, type of carbohydrate in the diet, feed
      processing, addition of lipids or ionophores to the diet, and alterations in the
      ruminal microflora. Manipulation of these factors can reduce methane emissions
      from cattle. Many techniques exist to quantify methane emissions from individual
      or groups of animals. Enclosure techniques are precise but require trained
      animals and may limit animal movement. Isotopic and nonisotopic tracer techniques
      may also be used effectively. Prediction equations based on fermentation balance
      or feed characteristics have been used to estimate methane production. These
      equations are useful, but the assumptions and conditions that must be met for
      each equation limit their ability to accurately predict methane production.
      Methane production from groups of animals can be measured by mass balance,
      micrometeorological, or tracer methods. These techniques can measure methane
      emissions from animals in either indoor or outdoor enclosures. Use of these
      techniques and knowledge of the factors that impact methane production can result
      in the development of mitigation strategies to reduce methane losses by cattle.
      Implementation of these strategies should result in enhanced animal productivity
      and decreased contributions by cattle to the atmospheric methane budget.

PMID- 8567487
TI  - Impact of composition manipulation on lean lamb production in the United States.
AB  - At present less than 30% of the market lambs slaughtered in the United States
      meet the requirements for leanness and muscling as specified in the "Certified
      Fresh American Lamb" program established in 1990 by the American Sheep Industry
      Association (ASI). Carcass composition of slaughter lambs is determined by stage
      of growth relative to mature size, genotype, sex, and matching dietary nutriment
      to nutrient requirements for lean tissue growth. On the average, current
      production strategies produce carcasses that contain excessive amounts of fat,
      impeding optimized efficiency at all levels of production. Use of large-mature
      size terminal sires, feeding rumen-escape dietary protein, feeding intact males,
      and slaughtering at appropriate weights all improve composition of gain.
      Improvements of 10 to 20% in rates of gain and efficiency of nutrient use and
      similar reductions in feed cost can be achieved with each of these management
      strategies. Results from several experiments demonstrate that these effects are
      additive and provide a measure of the true genetic capacity for protein accretion
      rate in growing lambs. Adoption of these management strategies will allow lambs
      to be slaughtered at a younger age, which may improve meat quality and
      concurrently reduce the amount of nitrogen waste returned to the environment.
      Potential for further manipulation of composition exists through more accurately
      defining nutrient requirements of growing lambs and through use of metabolism
      modifiers. Maintaining a competitive, profitable, and sustainable sheep industry
      depends on continued improvement of production efficiency, preferably in systems
      with high reproductive rates.

PMID- 8567488
TI  - Instructing the animal physiology graduate student in human assisted reproductive
      technology.
AB  - Animal physiology graduate students provide an excellent personnel resource for
      laboratories performing human assisted reproductive technology (ART) procedures.
      However, the basic training of these students falls short of what is required for
      this highly specialized field. We designed a course to enhance their education in
      this area via classroom and hands-on laboratory instruction in a hospital and
      university setting. Topics covered in the course included in vitro maturation, in
      vitro fertilization, embryo culture, embryo transfer, quality control, quality
      assurance, micromanipulation, and cryopreservation. These techniques were applied
      to a group project to evaluate the influence of spermatozoal quality and quantity
      on early embryonic development in cattle and humans. Student grades were based on
      1) oral and written examinations; 2) demonstrated competency in laboratory
      techniques; 3) presentation of class project data at a state academy of science
      meeting; and 4) initiative, determination, and interest in the coursework. Three
      aspects of the course stood out as very positive. First, the team approach to
      accomplishing a class project was new to some of the graduate students. Second, a
      bond was formed between hospital- and university-based faculty that did and will
      continue to foster unique teaching and research opportunities between the two
      groups. Third, the opportunity for students to present research data in a formal
      setting was very rewarding. This course made the students keenly aware of the
      many aspects of ART and provided them with specialized skills that should make
      them more marketable in the field of reproductive technology.

PMID- 8567489
TI  - Cultural conditions for production of glucoamylase from Lactobacillus amylovorus
      ATCC 33621.
AB  - Lactobacillus amylovorus ATCC 33621 is an actively amylolytic bacterial strain
      which produces a cell-bound glucoamylase (EC 3.2.1.3). Conditions of growth and
      glucoamylase production were investigated using dextrose-free de Man-Rogosa
      Sharpe (MRS) medium in a 1.5 l fermenter, with varying dextrin concentration (0.1
      1.5% (w/v)), pH (4.5-6.5) and temperature (25-55 degrees C). Cell extracts were
      prepared by subjecting cells to treatment with a French Pressure cell in order to
      release intracellular proteins. Glucoamylase activity was then assayed. The
      effects of pH (4.0-9.0), temperature (15-85 degrees C) and substrate (dextrin and
      starch, 0-2% w/v) concentration on crude enzyme activity were investigated.
      Optimal growth was obtained in MRS medium containing 1% (w/v) dextrin, at pH 5.5
      and 37 degrees C. Glucoamylase production was maximal at the late logarithmic
      phase of growth, during 16-18 h. Crude enzyme had a pH optimum of 6.0 and
      temperature optimum of 60 degrees C. With starch as the substrate, maximal
      activity was obtained at a concentration of 1.5% (w/v). The effects of ions and
      inhibitors on glucoamylase activity were also investigated. Enzyme activity was
      not significantly influenced by Ca2+ and EDTA at 1 mmol l-1 concentration;
      however Pb2+ and Co2+ were found to inhibit the activity at concentrations of 1
      mmol l-1. The crude enzyme was found to be thermolabile when glucoamylase
      activity decreased after about 10 min exposure at 60 degrees C. This property can
      be exploited in the brewing of low calorie beers where only mild pasteurization
      treatments are used to inactivate enzymes. The elimination of residual enzyme
      effect would prevent further maltodextrin degradation and sweetening during long
      term storage, thus helping to stabilize the flavour of beer.

PMID- 8567490
TI  - The antimicrobial activity of lactic acid bacteria from fermented maize (kenkey)
      and their interactions during fermentation.
AB  - A total of 241 lactic acid bacteria belonging to Lactobacillus plantarum,
      Pediococcus pentosaceus, Lactobacillus fermentum/reuteri and Lactobacillus brevis
      from various processing stages of maize dough fermentation were investigated.
      Results indicated that each processing stage has its own microenvironment with
      strong antimicrobial activity. About half of the Lact. plantarum and practically
      all of the Lact. fermentum/reuteri investigated were shown to inhibit other Gram
      positive and Gram-negative bacteria, explaining the elimination of these
      organisms during the initial processing stages. Further, widespread microbial
      interactions amounting to 85% to 18% of all combinations tested were demonstrated
      amongst lactic acid bacteria within the various processing stages, i.e. raw
      material, steeping, 0 h and 48 h of fermentation, explaining the microbial
      succession taking place amongst lactic acid bacteria during fermentation. The
      antimicrobial effect was explained by the combined effect of acids, compounds
      sensitive to proteolytic enzymes and other compounds with antimicrobial activity
      with the acid production being the most important factor. The pattern of
      antimicrobial factors was not species-specific and the safety and storage
      stability of fermented maize seem to depend on a mixed population of lactic acid
      bacteria with different types of antimicrobial characteristics. This means that
      introduction of pure cultures as starters may impose a risk to the product.

PMID- 8567491
TI  - Random amplified polymorphic DNA and restriction enzyme analysis of PCR amplified
      rDNA in taxonomy: two identification techniques for food-borne yeasts.
AB  - The random amplified polymorphic DNA (RAPD) assay and the restriction enzyme
      analysis of PCR amplified rDNA are compared for the identification of the common
      spoilage yeasts Zygosaccharomyces bailii, Z. rouxii, Saccharomyces cerevisiae,
      Candida valida and C. lipolytica. Both techniques proved to be adequate tools for
      yeast identification. Since the RAPD does provide less stable patterns than
      restriction enzyme analysis of PCR amplified rDNA, and a large amount of data had
      to be compared without data reduction, Principal Component Analysis (PCA) was
      applied successfully for clustering the RAPD patterns. The success of PCA is
      highly influenced by the primer used in RAPD and the amount of reference samples.
      A large amount of reference samples improves the performance of clustering in
      PCA. The primer of choice was shown to be important with respect to the
      discriminatory power of the RAPD method. Some primers used enabled discrimination
      on the subspecies level. The results collected with both typing methods justify
      the conclusion that the present typing system can be applied for taxonomical
      purposes.

PMID- 8567492
TI  - Degradation and fermentation of fructo-oligosaccharides by oral streptococci.
AB  - Fructo-oligosaccharides (FOS) are claimed to have a positive effect on the
      intestinal flora. They are being used in functional foods in Japan and Europe.
      This group have tested the degradation of two commercial FOS preparations by oral
      streptococci in order to predict the cariogenicity of these products. Both
      preparations could be fermented to some extent by the species of oral
      streptococci tested. The enzymes necessary for the degradation of FOS were
      inducible. Each strain showed a specific degradation pattern. All strains,
      particularly Streptococcus mutans rapidly produced acid, mainly lactic acid.
      Streptococcus mitis also produced high concentrations of acetic acid. Plaque
      formation by Strep. mutans was similar to the sucrose control. It is concluded
      that FOS are cariogenic to a similar extent as sucrose.

PMID- 8567493
TI  - Assessment of biological activity and fate of organic compounds in a reactor for
      the measurement of biodegradable organic carbon in water.
AB  - A new, rapid method for the determination of biodegradable dissolved organic
      carbon (BDOC), especially suited to water industry needs, was recently proposed
      by the authors. This dynamic method measured the BDOC of circulating water
      continuously pumped over a biofilm attached to a special support (sinterized
      porous glass) that fills a system of two glass columns. The BDOC value
      corresponds to the difference in dissolved organic carbon (DOC) between inflow
      and outflow water samples. The analytical results are not significantly different
      from those of other bioassays that use indigenous bacteria, and the total
      duration of the analysis is less than 3 h. However, a problem common to all the
      BDOC methods based on attached bacteria is the extent to which the decrease in
      DOC during the BDOC analysis is due to true biodegradation or to adsorption of
      organic matter to the reactor. In the present study, a reasonable support is
      provided for the hypothesis that this decrease, at least in the dynamic method,
      is predominantly due to microbiological activity. After comparing the support
      (sinterized porous glass) with a good physical adsorbent (granular activated
      carbon), the influence of temperature, residual chlorine and sodium azide on the
      reactor performance was tested, and a sensitivity only attributable to biological
      activity was observed. Another set of experiments were performed to assess the
      fate and specific elimination of different organic substances, explicable
      assuming that biodegradation processes were involved.

PMID- 8567494
TI  - Polymerase chain reaction for verification of fluorescent colonies of Erwinia
      chrysanthemi and Pseudomonas putida WCS358 in immunofluorescence colony staining.
AB  - The potential of polymerase chain reaction (PCR) for verifying the identity of
      colonies stained by the immunofluorescence colony-staining (IFC) procedure was
      investigated. Using primers directed against conserved sequences of the pectate
      lyase-genes coding for isozymes PLa, PLd and PLe of Erwinia chrysanthemi, the
      authors confirmed the identity of 96% of 20 fluorescent target colonies, punched
      from IFC-stained samples with pure cultures. In pour plates with mixtures of Erw.
      chrysanthemi and non-target colonies from potato peel extracts, the identity of
      90% of 113 target colonies was confirmed. Using primers directed against
      sequences of the ferric-pseudobactin receptor gene pupA of Pseudomonas putida
      WCS358, the identity of 96% of 22 target colonies was confirmed in IFC-stained
      samples with pure cultures. In pour plates with mixtures of Ps. putida WCS358 and
      non-target bacteria from compost extracts, the identity of 59% of 108 fluorescent
      colonies was confirmed by PCR. It was shown that components from non-target
      bacteria lowered the threshold level of PCR for Ps. putida WCS358 100-fold.

PMID- 8567495
TI  - Dyes as fungal inhibitors: effect on colony enumeration.
AB  - The effects of three dyes on the colony enumeration of nine fungal strains
      (including members of the Deuteromycetes and Zygomycetes) in pure and mixed
      cultures were investigated. Using malt extract agar as basal and control medium,
      the following dyes and concentrations were assayed: auramine (25 ppm), gentian
      violet (5 ppm) and malachite green (1 ppm). The chemicals commonly used in
      commercial media dichloran (2 ppm) and rose bengal (50 ppm) were included in the
      study as reference mould-spreading inhibitors. Higher counts were usually
      obtained in the media containing dichloran, rose bengal or auramine, including
      the control medium in the absence of chemical when the mixed-conidium inocula did
      not include a spreading mould. Nevertheless in most cases no significant
      differences were observed between them. Malachite green (1 ppm) performed mainly
      as a strong inhibitor of spreading moulds, only allowing adequate colony
      development and recoveries of both Fusarium and Aspergillus strains tested.

PMID- 8567496
TI  - Running performance and cardiovascular capacity are not impaired in creatine
      depleted rats.
AB  - Several published reports have indicated that derangement of the
      phosphocreatine/creatine (Cr) energy-buffering system via Cr analogue feeding
      results in cardiomyopathy when cardiac performance is assessed in vitro. The
      present study was designed to examine indexes of cardiac performance in rats that
      have been chronically Cr depleted. Adult (180 +/- 4 g) rats were assigned to a
      normal diet (ND) (n = 8) or a Cr-depletion diet (CD) group (n = 10). After 61 +/-
      1 days of ad libitum feeding, measurements of steady-state exercise O2
      consumption were made. Hemodynamic indexes were then assessed during incremental
      running to peak sustained levels. Rats were then killed and the left ventricle
      was excised. In the CD group Cr was depleted 82% and V1 isomyosin decreased while
      V2 increased. O2 consumption during steady-state running was not different in CD
      rats. The respiratory exchange ratios of CD rats reflected a bias toward fat
      utilization during the latter stages of prolonged exercise. The exercise heart
      rates and peak systolic blood pressures of CD rats were slightly lower than those
      of ND rats. Both negative and positive rates of left ventricular pressure
      development were significantly reduced at all running speeds in the CD rats. CD
      rats were capable of exercise performance equal to that of ND animals. The
      hemodynamic and metabolic data suggest that the adaptations seen in the CD
      animals may be similar to those reported after endurance training. These results
      indicate that chronic Cr depletion does not impair either the circulatory or
      exercise capacity of rodents.

PMID- 8567497
TI  - An anatomic and physiological model of hepatic vascular system.
AB  - Hepatic function can be characterized by the activity/time curves obtained by
      imaging the aorta, spleen, and liver. Nonparametric deconvolution of the
      activity/time curves is clinically useful as a diagnostic tool in determining
      organ transit times and flow fractions. The use of this technique is limited,
      however, because of numerical and noise problems in performing deconvolution.
      Furthermore, the interaction of part of the tracer with the spleen and
      gastrointestinal tract, before it enters the liver, further obscures
      physiological information in the deconvolved liver curve. In this paper, a
      mathematical relationship is derived relating the liver activity/time curve to
      portal and hepatic behavior. The mathematical relationship is derived by using
      transit time spectrum/residence time density theory. Based on this theory, it is
      shown that the deconvolution of liver activity/time curves gives rise to a
      complex combination of splenic, gastrointestinal, and liver dependencies. An
      anatomically and physiologically plausible parametric model of the hepatic
      vascular system has been developed. This model is used in conjunction with
      experimental data to estimate portal, splenic, and hepatic physiological blood
      flow parameters for eight normal volunteers. These calculated parameters, which
      include the portal flow fraction, the splenic blood flow fraction, and blood
      transit times are shown to adequately correspond to published values. In
      particular, the model of the hepatic vascular system identifies the portal flow
      fraction as 0.752 +/- 0.022, the splenic blood flow fraction as 0.180 +/- 0.023,
      and the liver mean transit time as 13.4 +/- 1.71 s. The model has also been
      applied to two portal hypertensive patients. The variation in some of the model
      parameters is beyond normal limits and is consistent with the observed pathology.

PMID- 8567498
TI  - Scaling, normalizing, and per ratio standards: an allometric modeling approach.
AB  - The practice of scaling or normalizing physiological variables (Y) by dividing
      the variable by an appropriate body size variable (X) to produce what is known as
      a "per ratio standard" (Y/ X), has come under strong criticism from various
      authors. These authors propose an alternative regression standard based on the
      linear regression of (Y) on (X) as the predictor variable. However, if linear
      regression is to be used to adjust such physiological measurements (Y), the
      residual errors should have a constant variance and, in order to carry out
      parametric tests of significance, be normally distributed. Unfortunately, since
      neither of these assumptions appear to be satisfied for many physiological
      variables, e.g., maximum oxygen uptake, peak and mean power, an alternative
      approach is proposed of using allometric modeling where the concept of a ratio is
      an integral part of the model form. These allometric models naturally help to
      overcome the heteroscedasticity and skewness observed with per ratio variables.
      Furthermore, if per ratio standards are to be incorporated in regression models
      to predict other dependent variables, the allometric or log-linear model form is
      shown to be more appropriate than linear models. By using multiple regression,
      simply by taking logarithms of the dependent variable and entering the
      logarithmic transformed per ratio variables as separate independent variables,
      the resulting estimated log-linear multiple-regression model will automatically
      provide the most appropriate per ratio standard to reflect the dependent
      variable, based on the proposed allometric model.

PMID- 8567499
TI  - Effect of analyzer on determination of mixed venous PCO2 and cardiac output
      during exercise.
AB  - Cardiac output (CO) during exercise can be determined noninvasively by using the
      indirect Fick CO2-rebreathing technique. CO2 measurements for this technique are
      usually performed with an infrared analyzer (IA) or mass spectrometer (MS).
      However, IA CO2 measurements are susceptible to underreading in the face of high
      O2 concentrations because of collision broadening. We compared an IA (Ametek
      model CD-3A) with a MS (Marquette model MGA-1100) to see the effect this would
      have on mixed venous PCO2 (PVCO2) and CO measurements. After calibration with
      room air and a gas mixture of 5% CO2-12% O2-83% N2, both devices were tested with
      three different gas mixtures of CO2 in O2. For each gas mixture, IA gave lower
      CO2 values than did the MS (4.1% CO2: IA, 3.85 +/- 0.01% and MS, 4.13 +/- 0.01%;
      9.2% CO2: IA, 8.44 +/- 0.07% and MS, 9.19 +/- 0.01%; 13.8% CO2: IA, 12.57 +/-
      0.15% and MS, 13.82 +/- 0.01%). Warming and humidifying the gases did not alter
      the results. The IA gave lower values than did the MS for eight other medical
      gases in lower concentrations of O2 (40-50%). Equilibrium and exponential
      rebreathing procedures were performed. Values determined by the IA were > 10%
      higher than those determined by the MS for both rebreathing methods. We conclude
      that all IAs must be checked for collision broadening if they are to be used in
      environments where the concentration of O2 is > 21%. If collision broadening is
      present, then either a special high O2-CO2 calibration curve must be constructed,
      or the IA should not be used for both arterial PCO2 and PVCO2 estimates because
      it may produce erroneously low PVCO2 values, with resultant overestimation of CO.

PMID- 8567500
TI  - Critique of conceptual basis of diffusing capacity estimates: a finite element
      analysis.
AB  - We present a simple geometric model of a pulmonary capillary segment containing a
      variable number of red blood cells. The pattern of CO transfer from alveolar air
      to capillary red blood cells in this model is accurately computed by a finite
      element method and used to explore conceptual flaws in the Roughton-Forster (RF)
      and morphometric methods of estimating pulmonary diffusing capacity for CO. The
      CO uptakes calculated by the finite element method at two alveolar O2 tensions
      are introduced into the RF model to determine whether the anatomically defined
      membrane component of diffusing capacity for CO (DmCO) and pulmonary capillary
      blood volume (Vc) are recovered. The same capillary model is also subjected to
      standard morphometric analysis. Results are compared at different levels of
      capillary hematocrit (Hct). The RF method accurately recovers DmCO and Vc at a
      low Hct but modestly overestimates DmCO and underestimates Vc at higher Hct;
      errors arise because conductance of the tissue-plasma membrane for CO varies with
      alveolar O2 tension. The morphometric method seriously overestimates DmCO because
      the true tissue-plasma resistance to diffusion is underestimated and the
      effective membrane utilized for diffusion is overestimated; these errors are
      accentuated by a low Hct.

PMID- 8567501
TI  - Override of spontaneous respiratory pattern generator reduces cardiovascular
      parasympathetic influence.
AB  - We investigated the effects of voluntary control of breathing on autonomic
      function in cardiovascular regulation. Variability in heart rate was compared
      between 5 min of spontaneous and controlled breathing. During controlled
      breathing, for 5 min, subjects voluntarily reproduced their own spontaneous
      breathing pattern (both rate and volume on a breath-by-breath basis). With the
      use of this experimental design, we could unmask the effects of voluntary
      override of the spontaneous respiratory pattern generator on autonomic function
      in cardiovascular regulation without the confounding effects of altered
      respiratory pattern. Results from 10 subjects showed that during voluntary
      control of breathing, mean values of heart rate and blood pressure increased,
      whereas fractal and spectral powers in heart rate in the respiratory frequency
      region decreased. End-tidal PCO2 was similar during spontaneous and controlled
      breathing. These results indicate that the act of voluntary control of breathing
      decreases the influence of the vagal component, which is the principal
      parasympathetic influence in cardiovascular regulation.

PMID- 8567502
TI  - Chaotic mixing of alveolated duct flow in rhythmically expanding pulmonary
      acinus.
AB  - We examined the effects of rhythmic expansion of alveolar walls on fluid
      mechanics in the pulmonary acinus. We generated a realistic geometric model of an
      alveolated duct that expanded and contracted in a geometrically similar fashion
      to simulate tidal breathing. Time-dependent volumetric flow was generated by
      adjusting the proximal and distal boundary conditions. The low Reynolds number
      velocity field was solved numerically over the physiological range. We found that
      for a given geometry, the ratio of the alveolar flow (QA) to the ductal flow (QD)
      played a major role in determining the flow pattern. For larger QA/QD (as in the
      distal region in the acinus), the flow in the alveolus was largely radial. For
      small QA/QD (as in the proximal region in the acinus), the flow in the alveolus
      was slowly rotating and the velocity field near the alveolar opening was complex
      with a stagnation saddle point typical of chaotic flow structures. Performing
      Lagrangian fluid particle tracking, we demonstrated that in such a flow structure
      the motion of fluid could be highly complex, irreversible, and unpredictable even
      though it was governed by simple deterministic equations. These are the
      characteristics of chaotic flow behavior. We conclude that because of the unique
      geometry of alveolated duct and its time-dependent motion associated with tidal
      breathing, chaotic flow and chaotic mixing can occur in the lung periphery. Based
      on these novel observations, we suggest a new approach for studying acinar fluid
      mechanics and aerosol kinetics.

PMID- 8567503
TI  - Oxidants and antioxidants in exercise.
AB  - There is consistent evidence from human and animal studies that strenuous
      physical exercise may induce a state wherein the antioxidant defenses of several
      tissues are overwhelmed by excess reactive oxygen. A wide variety of
      physiological and dietary antioxidants act in concert to evade such a stress.
      Submaximal long-duration exercise training may augment the physiological
      antioxidant defenses in several tissues; however, this enhanced protection may
      not be sufficient to completely protect highly fit individuals from exhaustive
      exercise-induced oxidative stress. Regular physical activity in association with
      dietary habits that ensure adequate supply of a combination of appropriate
      antioxidants may be expected to yield desirable results. The significance of this
      area of research, current state of information, and possibilities of further
      investigation are briefly reviewed.

PMID- 8567504
TI  - Invited editorial on "Ventilatory effects of specific carotid body hypocapnia in
      dogs during wakefulness and sleep".

PMID- 8567505
TI  - Ventilatory effects of specific carotid body hypocapnia in dogs during
      wakefulness and sleep.
AB  - We used extracorporeal perfusion of the vascularly isolated carotid sinus region
      to determine the effects of specific carotid body chemoreceptor hypocapnia
      alkalosis on ventilatory control in the unanesthetized dog. Eight female dogs
      were studied during wakefulness, non-rapid-eye-movement (NREM) sleep, and rapid
      eye movement (REM) sleep. Carotid body perfusions lasted from 1 to 2 min, and
      each trial was preceded by a 1-min control period. Two levels of carotid body
      hypocapnia were employed, approximately 7 and 14 Torr below eupneic levels in a
      given dog. We found that 1) During wakefulness and NREM sleep, carotid body
      hypocapnia caused reduced tidal volume (VT) but not apnea or expiratory time
      prolongation. 2) The inhibition of ventilation in response to carotid body
      hypocapnia was graded below normocapnia, showing the highest sensitivity at
      carotid body PCO2 near 7 Torr below eupneic values. Inhibition reached a maximum
      near 14 Torr below the eupneic level; VT, inspiratory minute ventilation (VI),
      and VT-to-inspiratory time ratio fell 31, 23, and 27% in wakefulness and 30, 23,
      and 30% in NREM sleep. 3) Reductions in ventilation in response to carotid body
      hypocapnia are lessened but still persist throughout perfusion (up to at least
      130 s) despite significant systemic hypercapnia. 4) During REM sleep, carotid
      body hypocapnia had no consistent inhibitory effect on ventilation until carotid
      body PCO2 was reduced to values near 14 Torr below the eupneic level, at which
      point ventilation was similar to wakefulness and NREM. 5) Moderate carotid body
      hypocapnia was as effective as carotid body hyperoxia in reducing VT and VI. We
      conclude that carotid body hypocapnia-alkalosis can significantly inhibit eupneic
      VT and ventilation during wakefulness and NREM sleep and, if the hypocapnia is
      severe enough, during REM sleep.

PMID- 8567506
TI  - Endothelin-1 contributes to antigen-induced airway hyperresponsiveness.
AB  - Endothelin A (ETA)-receptors mediate ET-1 contractions of ovine airway smooth
      muscle. Therefore, the ETA-receptor antagonist, BQ-123, was used to test the
      hypothesis that ET-1 contributes to antigen-induced airway responses in sheep
      allergic to Ascaris suum. We first established the protective effect of BQ-123 by
      demonstrating that BQ-123 given as an aerosol (0.3 or 1.0 mg/kg in 3 ml buffer)
      or by continuous intravenous infusion (100 micrograms.kg-1.min-1) significantly
      blocked the bronchoconstriction to aerosolized ET-1 (0.2-200 micrograms/ml). To
      determine whether ET-1 contributed to antigen-induced airway responses, BQ-123
      was given either as an intravenous infusion (100 micrograms.kg-1.min-1) beginning
      30 min before and continuing for 8 h after antigen challenge or as an aerosol (1
      mg/kg in 3 ml buffer) 30 min before and 4, 8, and 24 h after antigen challenge.
      Neither treatment with intravenous infusion nor aerosolized BQ-123 blocked the
      immediate antigen-induced bronchoconstriction, but both treatments significantly
      reduced the late response (approximately 50%). The treatments with aerosolized BQ
      123 also blocked the antigen-induced airway hyperresponsiveness to inhaled
      carbachol seen 24 h after challenge. Subsequently, we found that sheep developed
      airway hyperresponsiveness to inhaled carbachol at 4 and 24 h after ET-1
      challenge, an effect that was blocked by aerosolized BQ-123. We conclude that in
      allergic sheep 1) aerosolized ET-1 causes bronchoconstriction, in part, by
      stimulation of ETA-receptors, 2) ET-1 is released in the airways after antigen
      challenge, and 3) this peptide contributes to the severity of the allergic
      responses, probably by increasing airway smooth muscle responsiveness.

PMID- 8567507
TI  - Augmented mesenteric and renal vasoconstriction during exercise in senescent
      Fischer 344 rats.
AB  - The purpose of this study was to test the hypothesis that vasoconstriction in the
      mesenteric and renal circulations is greater at both submaximal and maximal
      exercise intensities with advancing age. Arterial blood pressure, heart rate, and
      mesenteric, renal, and iliac (hindlimb) artery blood flow velocities were
      measured before and during graded treadmill exercise in mature (12 mo) and
      senescent (24 mo) male Fischer 344 rats. During treadmill running at mild,
      moderate, and maximal exercise intensities (approximately 45, 70, and 100% of
      maximal oxygen uptake), the increases in arterial pressure were similar in the
      mature and senescent animals, whereas heart rate rose less in the older group (P
      < 0.05). Mesenteric and renal flow velocities declined and vascular resistances
      increased from resting levels in both groups in response to graded exercise;
      however, the magnitudes of the increases in both mesenteric and renal vascular
      resistance were significantly augmented in the older rats at the moderate and
      maximal workloads. Hindlimb blood flow velocity increased and resistance declined
      from resting levels at each exercise intensity in both groups. In contrast to the
      visceral and renal adjustments, the magnitudes of the changes in both hindlimb
      flow and resistance were similar for the two age groups at all exercise
      intensities. These findings support the hypothesis that mesenteric and renal
      vasoconstriction is augmented in senescent Fischer 344 rats during exercise at
      moderate and maximal intensities but not at mild workloads. Despite these
      regional differences, the maintenance of arterial pressure is not altered at
      either submaximal or maximal exercise intensities with advancing age.

PMID- 8567508
TI  - Beat-by-beat forearm blood flow with Doppler ultrasound and strain-gauge
      plethysmography.
AB  - Simultaneous Doppler ultrasound estimates of brachial artery mean blood velocity
      (MBV) and venous occlusion strain-gauge plethysmography measures of forearm blood
      flow (FBF) were performed to determine the beat-by-beat relationship between the
      two methods and provide a method for flow calibration of Doppler MBV estimates.
      Such a calibration of Doppler MBV eliminates the need for knowledge of vessel
      cross-sectional area and angle of insonation while allowing for the
      quantification of limb blood flow. Six healthy subjects (5 men and 1 woman)
      performed 40 s of isometric forearm contraction at 35% maximal voluntary
      contraction with arterial inflow occluded. This resulted in elevated blood flow
      on relaxation and cuff deflation, and simultaneous beat-by-beat Doppler MBV and
      strain-gauge FBF measurements were then made over a period of 2-3 min as flow
      gradually decreased to resting levels. The r2 values for the fitted regression
      lines over a wide range of flows ranged from 0.87 to 0.98, and the mean square
      error terms ranged from 0.88 to 3.07 ml.100 ml-1.min-1. Significant day-to-day
      variation of the fitted regression parameters within subjects indicated that
      quantitative estimates of FBF from Doppler MBV require a calibration to be
      performed for each experiment. The finding of a strong linear relationship
      between Doppler MBV and venous occlusion strain-gauge plethysmography, as well as
      the marked beat-by-beat effect of cuff inflation on blood flow, confirms the
      importance of calibration on the same beats, not on adjacent segments of beats.

PMID- 8567509
TI  - Oxidation of exogenous [13C]galactose and [13C]glucose during exercise.
AB  - The present study examined the oxidation of exogenous galactose or glucose during
      prolonged submaximal cycling exercise. Eight highly trained volunteers exercised
      on two occasions on a cycle ergometer at 65% of maximal workload for 120 min,
      followed by a 60-min rest period and a second exercise bout of 30 min at 60%
      maximal workload. At random, subjects ingested a 8% galactose solution to which
      an [1-13C]galactose tracer was added or a 8% glucose solution to which an [U
      13C]glucose tracer was added. Drinks were provided at the end of the warm-up
      period (8 ml/kg) and every 15 min (2 ml/kg) during the first 120 min of the test.
      Blood and breath samples were collected every 30 and 15 min, respectively, during
      the test. The exogenous carbohydrate (CHO) oxidation was calculated from the
      13CO2/12CO2 ratio and CO2 production of the expired air. Peak exogenous CHO
      oxidation during exercise for galactose and glucose was 0.41 +/- 0.03 and 0.85 +/
      0.04 g/min, respectively. Total CHO and fat oxidation were not significantly
      different between the treatments. Forty-six percent of the ingested glucose was
      oxidized, whereas only 21% of the ingested galactose was oxidized. As a
      consequence, more endogenous CHO was utilized with galactose than with glucose
      (124.4 +/- 6.7 and 100.1 +/- 3.6 g, respectively). These results indicate that
      the oxidation rate of orally ingested galactose is maximally approximately 50% of
      the oxidation rate of a comparable amount of orally ingested glucose during 120
      min of exercise.

PMID- 8567510
TI  - Enlargement of the lateral pharyngeal fat pad space in pigs increases upper
      airway resistance.
AB  - Because the upper airway is partially enclosed in a rigid boundary, enlargement
      of soft tissue structures within this boundary could narrow the airway. The
      purpose of this study was to determine whether enlargement of the soft tissue
      space in the region of the lateral pharyngeal fat pad would increase pharyngeal
      resistance and narrow the retropalateal upper airway. In five young male
      anesthetized pigs, we inserted balloon occlusion catheters in the lateral
      pharyngeal fat pad under computerized tomographic scan guidance. We measured
      pharyngeal resistance with a pharyngeal catheter and a tightly fitting face mask
      before and after inflation of the balloons. We also measured pharyngeal airway
      cross-sectional area before and after inflation of the balloons. In all pigs,
      balloon inflation significantly increased pharyngeal resistance and significantly
      decreased the area of the retropalateal airway. We conclude that enlargement of
      the soft tissue space in the region of the lateral pharyngeal fat pad increases
      pharyngeal resistance and narrows the retropalateal airway in anesthetized pigs.

PMID- 8567511
TI  - Thermal stresses reduce natural killer cell cytotoxicity.
AB  - The effects of different ambient temperatures (Ta) on the splenic natural killer
      (NK) cell activity, effector-target cell conjugation activity, and NK cell
      numbers were assessed in male inbred C3H/HeNCrj mice (7-10 wk old). The splenic
      NK cytotoxic activities were examined in a 4-h 51Cr release assay in mouse spleen
      cells that were obtained 1, 2, 4, 8, or 16 days after exposure to Ta of 22, 4, or
      35 degrees C. The percentage of conjugating lymphocytes was calculated by
      counting the number of single lymphocytes bound to single target cells per 400
      effector cells. The numbers of NK cells were expressed by the percentage of 5E6
      positive cells. The 5E6 identifies only a subset of NK cells. It was found that
      the splenic NK cell activity, the effector-target cell conjugation activity, or
      the NK cell number began to fall 1 day after cold (Ta 4 degrees C) or heat (Ta 35
      degrees C) stress. After a 16-day period of either cold or heat exposure, the
      fall in the splenic NK cell activity, the effector-target cell conjugation
      activity, or the number of 5E6-positive subsets of NK cells was still evident.
      Compared with those of the control group (Ta 22 degrees C), the cold-stressed
      mice had higher adrenal cortisol concentration and lower colonic temperature,
      whereas the heat-stressed animals had higher adrenal cortisol concentration and
      higher colonic temperature during a 16-day period of thermal exposure. However,
      neither cold nor heat stress affected both the body weight gain and the spleen
      weight in our mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567512
TI  - Effect of K+ channel blockade on fatigue in rat diaphragm muscle.
AB  - K+ channel blockers increase skeletal muscle force during twitch contractions;
      the present study determined whether K+ channel blockade also modulates force
      during longer term and higher frequency stimulation. 4-Aminopyridine (4-AP; 0.3
      mM) increased rat diaphragm force during twitch, 5-Hz and 20-Hz but not 100-Hz
      stimulation, and prolonged isometric contraction but not half-relaxation time. In
      response to continuous 5-Hz stimulation, the rate of force decline was
      accelerated by 4-AP so that over time force dropped below that of control muscle
      strips. In response to intermittent 20-Hz stimulation, 4-AP produced an early
      force potentiation; the 4-AP-induced force increase was maintained throughout
      repetitive stimulation despite an accelerated rate of force decline. In response
      to continuous 100-Hz stimulation, 4-AP did not affect rate of force decline.
      During 5- and 20-Hz stimulation, there was an interaction between 4-AP and
      duration of stimulation in prolonging contraction and especially half-relaxation
      time. Tetraethylammonium (10 mM) augmented diaphragm force less than did 4-AP,
      did not affect rate of force decline during 5-Hz stimulation, and did not
      interact with fatigue to prolong isometric twitch kinetics. These data indicate
      that K+ channel blockade with 4-AP increases diaphragm force at low to
      intermediate stimulation frequencies, may increase early force potentiation
      during repetitive contraction, and depending on stimulation pattern either
      accelerates or has no effect on rate of fatigue.

PMID- 8567513
TI  - Indomethacin does not alter natural killer cell response to 2.5 h of running.
AB  - The effect of 2.5 h of treadmill running at 75.6 +/- 0.9% maximal O2 uptake
      (VO2max) on natural killer (NK) cell cytotoxic activity (NKCA) was investigated
      in 22 experienced marathon runners (VO2max 57.9 +/- 1.1 ml.kg-1.min-1, age 38.7
      +/- 1.5 yr). Blood samples were taken before (0715) and immediately after
      exercise (1000), with three more samples taken during 6 h of recovery (1130,
      1300, and 1600). Ten sedentary controls (VO2max 34.7 +/- 1.0 ml.kg-1.min-1, age
      45.3 +/- 2.3 yr) sat in the laboratory during testing and had their blood sampled
      at the same time points. The pattern of change in NKCA over time was
      significantly different between groups [F(4,27) = 6.53; P = 0.001], with the
      runner's NKCA dropping 51-61% below preexercise levels throughout 6 h of
      recovery. Preincubation of blood mononuclear cells in vitro with indomethacin had
      no effect on the difference in pattern of change in NKCA between groups [F(4,17)
      = 8.59; P = 0.001] and did not attenuate the postexercise reduction in the
      runners. When NKCA was adjusted on a per-NK cell basis, group differences and the
      postexercise decline in NKCA were eliminated [F(4,80) = 0.65; P = 0.63]. Serum
      cortisol and plasma epinephrine in the runners were elevated relative to control
      subjects during recovery from exercise, but no significant correlation with
      changes in NK cells or NKCA was found. These data indicate that NKCA is decreased
      significantly during recovery from 2.5 h of running due to a numerical
      redistribution of NK cells.

PMID- 8567514
TI  - Metabolic availability of medium-chain triglycerides coingested with
      carbohydrates during prolonged exercise.
AB  - The present study examined the metabolic response to medium-chain triglycerides
      (MCTs) ingestion with or without carbohydrates (CHOs). Eight well-trained
      athletes cycled 4 x 180 min at 50% maximal work rate (57% maximal O2
      consumption). Subjects drank a bolus of 4 ml/kg at the start and 2 ml/kg every 20
      min during exercise of either a 15% (214 g) CHO solution (CHO trial), an
      equicaloric 149 g CHO-29 g MCT suspension (CHO+MCT trial), 214 g CHO [high CHO
      (HCHO)]-29 g MCT suspension (HCHO+MCT trial) or 29 g MCT solution (MCT trial).
      Exogenous MCT oxidation was measured by adding a [1,1,1-13C]trioctanoate tracer
      to the MCT oil. 13CO2 enrichment of breath samples were measured every 15 min.
      During the second hour (60- to 120-min period), the amount of MCT oxidized was
      72% of the amount ingested during the CHO+MCT trial, whereas during the MCT trial
      only 33% was oxidized. The rate of MCT oxidation increased more rapidly during
      the HCHO+MCT and CHO+MCT trials compared with the MCT trial, yet in all three
      cases the oxidation rate stabilized at 0.12 g/min during 120-180 min of exercise.
      It is concluded that more MCTs are oxidized when ingested in combination with
      CHOs. Data do confirm the hypothesis that oral MCTs might serve as an energy
      source in addition to glucose during exercise because the metabolic availability
      of MCTs was high during the last hour of exercise, with oxidation rates being
      approximately 70% of the ingestion rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567515
TI  - In vitro responses of lung arteries to acute hypoxia after NO synthase blockade
      or chronic hypoxia.
AB  - Responses to hypoxia of lung arteries (200-350 microns) from control (C) and
      chronically hypoxic (CH) rats were compared in a myograph before and after
      blockade of NO synthase with NG-nitro-L-arginine methyl ester (L-NAME). After
      precontraction with prostaglandin F2 alpha (PGF2 alpha), hypoxia caused a four
      phase tension change: brief dilation, transient contraction, prolonged dilation,
      and slow contraction (we studied the first three phases). In CH rats, the first
      dilation and first contraction were significantly reduced. After L-NAME, the
      first dilation was reduced in C rats and abolished in CH rats; thus the first
      phase is attributable to NO release and is affected by chronic hypoxia. The first
      contractile phase was significantly reduced by L-NAME in C but not in CH rats,
      where it was small. Thus NO synthase inhibition inhibits hypoxic constriction in
      isolated vessels, whereas it enhances hypoxic constriction in perfused lungs. The
      third dilator phase was unaffected by chronic hypoxia; it was increased after L
      NAME in CH rats. Thus, in vitro, responses to hypoxia are complex; there is a
      balance between two dilator and two constrictor processes.

PMID- 8567516
TI  - Analysis of low-frequency lung impedance in rabbits with nonlinear models.
AB  - Lung mechanics was studied in six paralyzed tracheotomized rabbits ventilated
      with a specially devised computer-controlled ventilator. The target flow waveform
      contained noninteger multiple frequencies ranging from 0.83 to 6-10 Hz and met a
      neither-sum-nor-difference criterion to minimize the effects of nonlinearity (B.
      Suki and K. Lutchen. IEEE Trans. Biomed. Eng. 39: 1142-1151, 1992). The actual
      flow, however, contained harmonics of the two lowest frequencies. Measurements
      were performed at mean airway pressure (Paw) levels of 8 and 12 hPa and during
      histamine-induced bronchoconstriction. Smooth impedance curves were observed in
      unchallenged rabbits at low mean Paw levels. In contrast, unrealistic impedance
      fluctuations, suggestive of cross talk from the unwanted frequency components in
      the flow input, were seen at high mean Paw levels and during acute
      bronchoconstriction. Model analysis was performed by using the actual flow signal
      as an input to various nonlinear models. The impedance fluctuations observed at
      high mean Paw levels were well simulated by a model featuring a volume-dependent
      elastance, and those observed after histamine were almost perfectly reproduced by
      a model where resistance increased with the reciprocal of lung volume. We
      conclude that impedance data biased by cross talk may provide useful information
      on the presence and nature of respiratory system nonlinearities.

PMID- 8567517
TI  - Temperature effects on ventilatory rate, heart rate, and preferred pedal rate
      during cycle ergometry.
AB  - According to the most customary exercise protocols, core temperature (Tc) rises
      in parallel with workload (WL) and experimental time. Physiological variables,
      however, may be related to each of these factors. To investigate effects of WL
      independent of experimental time and body temperature, we employed four moderate
      WLs in 4-min steps between 35 and 65% peak O2 uptake (VO2 peak) in randomized
      order. To investigate independent effects of body temperature, the same work
      protocol was performed both after resting in comfortable ambient temperature
      [control test (Cont)] and after a double cold exposure [precooling test (Pret)],
      where Tc and the temperature set point are decreased by approximately 0.6 and 0.3
      degrees C, respectively. Eight male subjects (24 +/- 1.9 yr, VO2 peak 4.9 +/- 0.5
      l/min) worked on a cycle ergometer in a climatic chamber. Heart rate (HR) and
      breathing frequency (BF), but not preferred pedal rate (PR), were positively
      correlated to Tc, the slopes amounting to 17 and 3.75 min-1/degree C for HR and
      BF, respectively. The regression appeared linear over the whole temperature
      range, and the regression lines were not shifted by precooling. PR was increased
      by time, but Pret-Cont differences of PR and Tc were inversely correlated (r = 
      0.50, P < 0.01). The effects of WL were highly significant on HR, O2 uptake, and
      rate of perceived exertion but not on BF, PR, and sweat rate. The relation of
      rate of perceived exertion to HR was shifted by precooling.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8567518
TI  - During acute hypercapnia vasopressin inhibits an angiotensin drive to ventilation
      in conscious dogs.
AB  - Intravenous infusion of arginine vasopressin (AVP) depresses the slope of the
      ventilatory response to CO2 during acute hypercapnia. We therefore tested the
      hypothesis that AVP V1-receptor blockade would increase the slope of the
      ventilatory response to CO2. After a 20-min control period, an AVP V1-receptor
      antagonist (d(CH2)5[Tyr(Me)2]AVP) was injected into six conscious resting dogs.
      Thirty minutes after AVP V1-receptor blockade, dogs were exposed to sequential 20
      min periods of 5 and 6.5% inspired CO2 in air. A second protocol (no AVP V1
      receptor blockade) was conducted as a control. As predicted, AVP V1-receptor
      blockade enhanced ventilation during inhalation of 6.5% CO2 in association with
      an increased metabolic rate and increased plasma angiotensin II (ANG II). In
      eupneic dogs, stimulation of respiration by AVP V1-receptor blockade is mediated
      by ANG II. A third protocol with ANG II-receptor blockade (intravenous infusion
      of saralasin) combined with AVP V1-receptor blockade indicated that ANG II
      mediated the increase in metabolism and the augmented ventilation during
      inhalation of 6.5% CO2. We conclude that during acute hypercapnia of sufficient
      magnitude, and perhaps duration, AVP inhibits an ANG II-mediated stimulation of
      metabolism and respiration.

PMID- 8567519
TI  - Hormonal changes in normal and polycythemic high-altitude natives.
AB  - Acute and chronic exposure to high-altitude (HA) hypoxia inhibits the renin
      angiotensin-aldosterone system and may modify the release of atrial natriuretic
      peptide (ANP) in sea-level (SL) natives. In HA natives, the release of these
      hormones could be influenced by changes in blood volume or pulmonary arterial
      pressure. Twenty-four men residing in La Paz, Bolivia, at 3,600 m were separated
      into two groups: one normocythemic (HAN; with hematocrit < 57%; n = 13) and the
      other polycythemic (HAP; with hematocrit > 57%; n = 11). A control group of 9 SL
      residents was studied in normoxia (SLN) as well as after 4 days spent at 4,350 m
      (SLH). The groups were tested for plasma active renin (PAR), plasma aldosterone
      concentration, ANP, and potassium and norepineprine concentrations at rest and
      after a maximal exercise. Pulmonary arterial systolic pressure was assessed by a
      Doppler technique. It was observed that PAR and plasma aldosterone concentration
      at rest and after exercise were lower in the SLH than in the SLN group. PAR and
      norepineprine concentration were higher among highlanders than in the SLN group.
      Renin response to exercise was normal among the HAN group and slightly decreased
      among the HAP group, and an exercise-induced increase in aldosterone was
      attenuated in both HA groups. Aldosterone response to renin was maintained among
      the SLH group but was attenuated in the HA groups, possibly owing to a protective
      mechanism against salt and water retention. Resting and exercise ANP was lower in
      the HA groups than in the SLN group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567520
TI  - Endotracheal intubation influences respiratory water loss during heat stress in
      young lambs.
AB  - To study the effect of intubation on respiratory water loss (RWL) during heat
      stress, 10 young nonsedated lambs were exposed to radiative heat stress both when
      intubated and when not. RWL, oxygen consumption (VO2), and carbon dioxide
      production were monitored continuously by using a flow-through system with a mass
      spectrometer for gas analysis. When the lambs were not intubated, heat stress
      caused RWL to increase by 218%, whereas VO2 and body temperature remained
      unchanged. When the lambs were intubated, heat stress caused RWL to increase by
      131% and VO2 to increase by 36%. On extubation during heat stress, RWL increased
      by 117 +/- 48% (standard error of the estimate) of the preextubation value and
      body temperature started to fall. This study shows that intubation reduces the
      ability of the lamb to increase RWL and heat loss during heat stress in a warm
      environment, possibly as an effect of exclusion of the nose and a reduction in
      dead space. After extubation, RWL increases markedly, a finding that might also
      be valid for intubated infants.

PMID- 8567521
TI  - Lesser vagal withdrawal during isometric exercise with age.
AB  - The tachycardia that accompanies isometric exercise decreases with age in humans;
      however, the mechanism of this decline is unknown. To determine whether less
      cardiac vagal withdrawal is associated with the age-related decrease in this
      response, we assessed high-frequency R-R interval variability (0.15-0.40 Hz), an
      index of cardiac vagal tone, before (control) and during isometric exercise to
      exhaustion in healthy young (21-29 yr; n = 12) and older (61-72 yr; n = 11) men.
      During control, the two groups did not differ in respiratory rate, mean arterial
      pressure, or heart rate, although the older subjects had a lower high-frequency
      amplitude (12.2 +/- 1.1 vs. 29.4 +/- 4.6 ms/Hz; P < 0.05). During isometric
      exercise, the respiratory rate and arterial pressure responses did not differ;
      however, the older men had a lower absolute heart rate and a smaller increase in
      heart rate, and only the young men demonstrated a significant decline in high
      frequency amplitude. The heart rate responses to exercise were correlated with
      the declines in high-frequency amplitude (initial, r = -0.808; midpoint, r = 
      0.714; peak, r = -0.632; all P < 0.005), which were, in turn, correlated with the
      control high-frequency amplitude (initial, r = -0.727; midpoint, r = -0.643;
      peak, r = -0.610; all P < 0.01). Thus smaller declines in high-frequency
      amplitude, related to lower baseline amplitude, corresponded to smaller increases
      in heart rate throughout isometric exercise. Therefore, we conclude that the
      smaller tachycardiac response to isometric exercise in older humans is associated
      with an inability to decrease cardiac vagal tone below an already reduced
      baseline level.

PMID- 8567522
TI  - Neurochemical control of tissue resistance in piglets.
AB  - Lung resistance may be influenced by chemoreceptor activity and modulated by
      inspiratory neural output; however, it is unknown whether the contractile
      elements of lung tissue participate in these changes during early development. In
      anesthetized paralyzed open-chest piglets, we measured phrenic electroneurogram,
      lung resistance (RL), and tissue resistance utilizing alveolar capsules to
      partition the hypercapnic and hypoxic responses of RL into tissue (Rti) and
      airway resistance (Raw) components. Inhalation of 7% CO2 significantly increased
      RL (7.4 +/- 0.5 to 11.3 +/- 0.6 cmH2O.l-1.s), Rti (5.2 +/- 0.5 to 6.9 +/- 0.5
      cmH2O.l-1.s), and Raw (2.2 +/- 0.2 to 4.4 +/- 0.4 cmH2O.l-1.s). Inhalation of 12%
      O2 caused more modest increases in RL, Rti, and Raw. Oscillations in tracheal and
      alveolar pressures appeared in synchrony with phrenic activity in response to
      both chemoreceptor stimuli. Cholinergic blockade eliminated these oscillations
      and significantly reduced the hypercapnic and hypoxic responses of RL, Rti, and
      Raw. These data demonstrate for the first time that hypercapnia and hypoxia
      elicit a cholinergically mediated increase in Rti which, just like the airway
      component of RL, is modulated by inspiratory neural output and is present during
      early development. Such coordination in neural function throughout the
      respiratory system may serve to optimize gas exchange during early postnatal
      life.

PMID- 8567523
TI  - Resistive training increases fat-free mass and maintains RMR despite weight loss
      in postmenopausal women.
AB  - Percent body fat increases with age and is often accompanied by a loss in muscle
      mass, strength, and energy expenditure. The effects of 16 wk of resistive
      training (RT) alone or with weight loss (RTWL) on strength (isokinetic
      dynamometer), body composition (dual-energy X-ray absorptiometry), resting
      metabolic rate (RMR) (indirect calorimetry), and sympathetic nervous system
      activity (catecholamines) were examined in 15 postmenopausal women (50-69 yr). RT
      resulted in significant improvements in upper and lower body strength in both
      groups (P < 0.01). The nonobese women in the RT group (n = 8) did not change
      their body weight or fat mass with training. In the obese RTWL group (n = 7),
      body weight, fat mass, and percent body fat were significantly decreased (P <
      0.001). Fat-free mass and RMR significantly increased with training in both
      groups combined (P < 0.05). There were no significant changes in resting
      arterialized plasma norepinephrine or epinephrine levels in either group with
      training. RT increases strength with and without weight loss. Furthermore, RT and
      RTWL increase fat-free mass and RMR and decrease percent fat in postmenopausal
      women. Thus, RT may be a valuable component of an integrated weight management
      program in postmenopausal women.

PMID- 8567524
TI  - Effects of hypoxia and vascular tone on endothelium-dependent and -independent
      responses in developing lungs.
AB  - Both increases and decreases in endothelium-derived nitric oxide (EDNO) activity
      have been described in the developing pulmonary vasculature. We hypothesized that
      differences in baseline vasomotor tone and/or oxygen tension may contribute to
      this variability. Pulmonary arterial dose responses to endothelium-dependent and 
      independent vasodilators acetylcholine (ACh) and sodium nitroprusside (SNP),
      respectively, were measured in indomethacin-treated lungs of 1- to 2-day-old (2D)
      and 1-mo-old (1M) lambs. During 4% O2 ventilation, baseline pulmonary vascular
      resistance (PVR) and the dilator response to both ACh and SNP were greater in 2D
      lungs. However, when baseline PVR values were matched at both ages during either
      hypoxia or infusion of a thromboxane mimetic under normoxic conditions,
      developmental differences in ACh-induced vasodilation were minimal. Furthermore,
      hypoxia itself did not alter the responses to ACh in 2D lungs. In contrast, SNP
      caused greater vasodilation in 2D than in 1M lungs regardless of baseline PVR.
      These data and studies suggest that whereas high PVR enhances EDNO synthesis,
      responsiveness to ENDO decreases as synthesis of ENDO increases in developing
      lungs studied under basal conditions.

PMID- 8567525
TI  - Effects of maturation on cell water, protein, and DNA content in ovine cerebral
      arteries.
AB  - The present study examined the effects of maturation on base-soluble protein, DNA
      content, and intracellular water volume in ovine cerebral arteries to evaluate
      these variables as references for normalization of levels of cellular
      constituents in studies of vascular maturation. With maturation, base-soluble
      protein per unit wet weight (measured by using the Bradford method) increased by
      27% to 46%, and cell volume (estimated as the ratio of cell water to DNA)
      increased by 53% to 97%. However, intracellular water per unit wet weight
      (calculated as the difference between total water measured by dehydration and
      extracellular water measured by using the extracellular marker [57Co]EDTA)
      increased by only 1% to 16%, because of maturation-related hypertrophy
      (quantitated histologically) combined with decreased cell number per unit wet
      weight (DNA content, quantitated by using Hoechst dye, decreased by 32% to 41%).
      In addition, the effects of maturation were artery specific: maturational
      increases in cell water and volume were more pronounced in common carotid than in
      cerebral arteries. These findings demonstrate that different methods of
      normalization can produce quantitatively opposite results in maturation-related
      studies. For cellular constituents, the most physiologically relevant
      normalization is relative to intracellular water volume, which yields units of
      apparent intracellular concentration. Because the relative content of
      intracellular water per unit wet weight changes little with maturation,
      normalization of levels of cellular constituents relative to wet weight provides
      a reasonable index of intracellular concentration. Clearly, no single approach is
      optimal for all studies, and the method of normalization should be carefully
      considered with regard to effects of maturation on vascular composition.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8567526
TI  - Slow component of O2 uptake during heavy exercise: adaptation to endurance
      training.
AB  - Seven untrained male subjects [age 25.6 +/- 1.5 (SE) yr, peak O2 uptake (VO2)
      3.20 +/- 0.19 l/min] trained on a cycle ergometer 4 days/wk for 6 wk, with the
      absolute training workload held constant for the duration of training. Before and
      at the end of each week of training, the subjects performed 20 min of constant
      power exercise at a power designed to elicit a pronounced slow component of VO2
      (end-exercise VO2-VO2 at minute 3 of exercise) in the pretraining session. An
      additional 20-min exercise bout was performed after training at this same
      absolute power output during which epinephrine (Epi) was infused at a rate of 100
      ng.kg-1.min-1 between minutes 10 and 20. After 2 wk of training, significant
      decreases in VO2 slow component, end-exercise VO2, blood lactate ([La-] and
      glucose concentrations, plasma Epi ([Epi]) and norepinephrine concentrations,
      ventilation (VE), and heart rate (HR) were observed (P < 0.05). Although the
      rapid attenuation of the VO2 slow component coincided temporally with reductions
      in plasma [Epi], blood [La-], and VE, the infusion of Epi after training
      significantly increased plasma [Epi] (delta 2.22 ng/ml), blood [La-] (delta 2.4
      mmol/l) and VE (delta 10.0 l/min) without any change in exercise VO2. We
      therefore conclude that diminution of the VO2 slow component with training is
      attributable to factors other than the reduction in plasma [Epi], blood [La-] and
      VE.

PMID- 8567527
TI  - Effects of fetal corticosteroid treatments on postnatal surfactant function in
      preterm lambs.
AB  - Effects of prenatal corticosteroid on the properties of surfactant have not
      previously been evaluated. A single ultrasound-guided fetal injection with 0.5
      mg/kg betamethasone 48 h before delivery of preterm lambs at 134- to 135-days
      gestation improved oxygenation, lowered the ventilatory pressures required to
      maintain arterial PCO2 between 30 and 40 Torr and decreased the protein leak of
      albumin from the intravascular to the alveolar space. This dose of glucocorticoid
      did not alter surfactant-saturated phosphatidylcholine pool sizes in the
      airspaces of preterm lambs. However, the treatment changed the characteristics of
      the surfactant recovered from the ventilated preterm lambs. The in vitro
      conversion from heavy to light subtype surfactant decreased from 59% for the
      saline-treated lambs to 37% for the corticosteroid-treated lambs after 180 min of
      surface area cycling (P < 0.02). Surfactant from the corticosteroid-treated lambs
      also increased the dynamic compliance of preterm surfactant-deficient rabbits
      more than did surfactant from the saline-treated lambs (P < 0.05). Prenatal
      treatment of preterm lambs with betamethasone improved the functional
      characteristics of surfactant without significant effects on the alveolar
      surfactant pool sizes.

PMID- 8567528
TI  - Bronchoscopic determination of ozone uptake in humans.
AB  - Measurements of ozone uptake efficiency in the human respiratory tract provide
      critical information toward understanding ozone dose-response characteristics. We
      measured ozone uptake efficiency by different regions of the respiratory tract
      between the mouth and bronchus intermedius in 10 healthy, resting, nonsmoking
      male and female subjects. The distal end of a bronchoscope was sequentially
      positioned at the bronchus intermedius (BI), main carina (CAR), upper trachea,
      and above the vocal cords. Ozone concentration was measured continuously at each
      sight using a rapid-responding ozone analyzer. During sampling subjects breathed
      through a mouthpiece connected to a pneumotachograph at a paced rate of 12
      breaths/min. Integration of the product of the flow and ozone concentrations
      during inspiration and expiration provided the ozone mass passing each anatomic
      location during each phase of respiration. On inspiration the uptake efficiencies
      of ozone by structures between the mouth and each location j (Em-j) were 0.176 +/
      0.037 (SE), 0.271 +/- 0.024, 0.355 +/- 0.030, and 0.325 +/- 0.031 for above the
      vocal cords, upper trachea, CAR, and BI, respectively. A significant effect of
      location on Em-j was found by analysis of variance (P < 0.0002). Pairwise
      comparisons showed that Em-j increased as the lung penetration increased except
      between CAR and BI, which was not significantly different.

PMID- 8567529
TI  - Partitioning of airway and lung tissue properties: comparison of in situ and open
      chest conditions.
AB  - The purpose of this study was to investigate under physiological breathing
      conditions whether airway and lung tissue properties are different in situ and in
      open-chest conditions. We measured lung input impedance in dogs from 0.2 to 8 Hz
      with an optimal ventilator waveform at four tidal volumes (VT; from 75 to 450 ml)
      in intact animals using an esophageal balloon as well as after opening the chest.
      The lung impedance from both conditions was partitioned into airway and tissue
      compartments as characterized by airway resistance and inertance (Iaw) and tissue
      damping (G) and elastance (H) parameters respectively. All parameters except Iaw
      depended to some extent on VT. The in situ tissue G and H slightly decreased with
      VT while in the open-chest condition; G decreased and H increased slightly with
      VT. We found small but significant differences between the mechanical properties
      of the airway and lung tissues in situ and in open-chest conditions. Over the
      total population, the G, airway resistance, and Iaw parameters were 13% (not
      significant), 35% (P < 0.001), and 31% (P < 0.001) smaller, respectively, in situ
      than in the open-chest condition. However, the H was 15% larger in situ (P <
      0.001). Although we cannot completely rule out certain artifacts, these
      differences most likely reflect real alterations in the lung due to the different
      configurations and possible differences in the distribution of pleural pressures
      in the two conditions. The G being smaller and E being larger in situ resulted in
      hysteresivity (G/H) 36% smaller in situ (P < 0.001).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8567530
TI  - Hypoxia, hypercapnia, and hypertension: their effects on pulsatile cerebral blood
      flow.
AB  - Pulsatile cerebral blood flow reflects characteristics of arterial blood pressure
      as well as the structure and mechanical properties of the cerebrovascular
      network. Although the effects of changes in systemic blood gases and blood
      pressure on mean cerebral flow are established, their effects on pulsatile
      cerebral blood flow are unknown. These studies assessed the effects of hypoxia
      hypercapnia (combined; both arterial PO2 and PCO2 approximately 55 Torr) and
      acute hypertension (+30-35 mmHg by aortic occlusion) on pulsatile cerebral blood
      flow in ketamine-anesthetized rabbits. We characterized the relationship between
      pulsatile systemic blood pressure (Millar catheter) and cerebral cortical
      capillary blood-flow (laser-Doppler) by calculating the transfer function, a
      frequency-domain expression that relates amplitudes and phase angles of flow
      output to those of the pressure input. During hypoxia-hypercapnia, mean flow
      increased 17% (P < 0.001), but the amplitude and contour of pulsatile cortical
      blood flow were unchanged (P > 0.10). Although aortic occlusion, during hypoxia
      hypercapnia as well as during normoxia-normocapnia, increased systemic pulse
      pressure by 40%, the amplitude of cortical flow pulsations was unaffected.
      Changes in dynamic properties of the cerebral vasculature (P < 0.0001 by analysis
      of the transfer function) minimized alterations in pulsatile cortical blood flow
      and thus intrabeat vessel wall stress during acute hypertension; on the basis of
      analysis of an electrical analogue, we propose that these changes reflect
      alterations in both resistance and compliance.

PMID- 8567531
TI  - Effects of acute exercise on hepatic lipogenic enzymes in fasted and refed rats.
AB  - The effects of an acute bout of prolonged exhaustive exercise on the activities
      of hepatic lipogenic enzymes have been investigated. Male Sprague-Dawley rats
      were randomly divided into three groups: fasted for 48 h without refeeding (FA)
      and fasted for 48 h and refed a diet high in fructose (RF) or in cornstarch (RC).
      One-half of each group of rats exercised on a treadmill at 20 m/min, 5% grade,
      until exhaustion and the other half rested for the same amount of time without
      food. Dietary intakes during refeeding were kept equal between the exercised and
      rested control animals. Activities of all hepatic lipogenic enzymes measured,
      i.e., fatty acid synthase (FAS), L-type pyruvate kinase (L-PK), ATP citrate
      lyase, malic enzyme, and glucose-6-phosphate dehydrogenase, were induced
      dramatically by fasting-refeeding and were significantly higher in the RF than in
      the RC rats (P < 0.05). FAS activity was increased 19- and 39-fold, respectively,
      in the RC and RF rats compared with the FA rats. Exercise decreased FAS activity
      to approximately one-third of the resting control value in both RC and RF rats (P
      < 0.05) but not in FA rats. L-PK activity was elevated by 55% in RC and 100% in
      RF rats compared with FA rats (P < 0.05). FA and RF rats also showed a reduction
      of L-PK activity with exercise. No significant alteration of other lipogenic
      enzymes was observed after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567532
TI  - Inhaled nitric oxide prevents the increase in pulmonary vascular permeability
      caused by hydrogen peroxide.
AB  - Given the interest in using inhaled nitric oxide (NO.) to treat acute lung injury
      and the importance of oxygen radicals in its pathogenesis, we studied the
      effects, in buffer-perfused isolated rabbit lungs, of inhaled NO. (24 ppm) on the
      injury caused by generating hydrogen peroxide with glucose and glucose oxidase
      (GOX). Experiments were performed at a constant pulmonary arterial pressure. GOX
      substantially augmented vascular permeability, as demonstrated by an increase in
      the lung-to-perfusate 125I-labeled albumin ratio, lavage-to-perfusate 125I
      albumin ratio, wet-to-dry lung weight ratio, and pulmonary vascular filtration
      coefficient. Lungs treated with inhaled NO. before perfusion with GOX had lung-to
      perfusate and lavage-to-perfusate 125I-albumin ratios that were not significantly
      different from control values and intermediate between the control and GOX
      groups. Inhaled NO. also prevented the increase in wet-to-dry lung weight ratio
      and pulmonary vascular filtration coefficient caused by GOX.. Thus inhaled NO.
      substantially reduced in the isolated lung the increase in pulmonary vascular
      permeability produced by the intravascular generation of hydrogen peroxide.

PMID- 8567533
TI  - Regulation of ventilatory capacity during exercise in asthmatics.
AB  - In asthmatic and control subjects, we examined the changes in ventilatory
      capacity (VECap), end-expiratory lung volume (EELV), and degree of flow
      limitation during three types of exercise: 1) incremental, 2) constant load (50%
      of maximal exercise capacity; 36 min), and 3) interval (alternating between 60
      and 40% of maximal exercise capacity; 6-min workloads for 36 min). The VECap and
      degree of flow limitation at rest and during the various stages of exercise were
      estimated by aligning the tidal breathing flow-volume (F-V) loops within the
      maximal expiratory F-V (MEFV) envelope using the measured EELV. In contrast to
      more usual estimates of VECap (i.e., maximal voluntary ventilation and forced
      expiratory volume in 1 s x 40), the calculated VECap depended on the existing
      bronchomotor tone, the lung volume at which the subjects breathed (i.e., EELV),
      and the tidal volume. During interval and constant-load exercise, asthmatic
      subjects experienced reduced ventilatory reserve, higher degrees of flow
      limitation, and had higher EELVs compared with nonasthmatic subjects. During
      interval exercise, the VECap of the asthmatic subjects increased and decreased
      with variations in minute ventilation, due in part to alterations in their MEFV
      curve as exercise intensity varied between 60 and 49% of maximal capacity. In
      conclusion, asthmatic subjects have a more variable VECap and reduced ventilatory
      reserve during exercise compared with nonasthmatic subjects. The variations in
      VECap are due in part to a more labile MEFV curve secondary to changes in
      bronchomotor tone. Asthmatics defend VECap and minimize flow limitation by
      increasing EELV.

PMID- 8567534
TI  - Metabolic responses of rat respiratory muscles to voluntary exercise training.
AB  - Voluntary wheel running for 4 or 8 wk was used to assess whether a volitional
      training stimulus would induce adaptations in the oxidative capacity [citrate
      synthase activity (CS)], glucose phosphorylation capacity [hexokinase activity
      (HK)], and glucose transporter protein level (GLUT-4) of rat respiratory muscles.
      Running distances averaged approximately 10-13 km/day over the final 5 wk of
      training. Peak oxygen consumption by the trained animals was 17% greater (P <
      0.05) than by age-matched sedentary control animals after 8 wk. CS, HK, and GLUT
      4 in soleus and plantaris muscles all increased because of exercise training. CS
      increased in the rectus abdominis (+17%), external oblique (+28%), and internal
      oblique (+17%) but not in the costal or crural diaphragm after 4 wk of training.
      However, after 8 wk, CS in the costal diaphragm was 39% greater than control but
      was unchanged in the crural diaphragm. Whereas HK was significantly greater than
      control in the costal diaphragm (+18%) and rectus abdominis (+54%) after 4 wk, 8
      wk of running were required for increases in HK in the external oblique (+17%)
      and internal oblique (+14%). HK in the crural diaphragm was not significantly
      altered by the exercise training. GLUT-4 did not change significantly in any of
      the respiratory muscles studied. These results indicate that significant
      adaptations in the glucose phosphorylation capacity and oxidative capacity of
      both inspiratory and expiratory muscles can take place in response to voluntary
      exercise. However, this same stimulus is not sufficient to cause an adaptive
      response in GLUT-4 protein level in these respiratory muscles.

PMID- 8567535
TI  - Pulmonary capillaries are more resistant to stress failure in dogs than in
      rabbits.
AB  - We previously showed that stress failure of pulmonary capillaries occurs at
      transmural pressures of approximately 50 cmH2O (40 mmHg) and above in rabbit
      lung. In this study, we examined whether pulmonary capillaries are more resistant
      to failure in dogs than in rabbits. This might be expected because of the greater
      athletic ability of dogs and therefore their presumably greater tolerance to
      large cardiac outputs and higher pulmonary vascular pressures. The lungs of 12
      anesthetized mongrel dogs [22.1 +/- 5.2 (SD) kg] were perfused in situ with
      autologous blood and then with saline-dextran (5 min) and glutaraldehyde solution
      (10 min), all three perfusions at the same preset transmural pressure of 32.5,
      72.5, 92.5, or 112.5 cmH2O. In dogs, the stress failure curves relating break
      number per millimeter of epithelium and endothelium were right shifted by
      approximately 40 cmH2O compared with rabbits. Blood-gas barrier thickness was
      significantly greater than in rabbits at 32.5 cmH2O, and unlike in rabbits,
      neither total nor interstitial thickness increased significantly with increasing
      pressure. These results indicate that pulmonary capillaries are more resistant to
      stress failure in dogs than rabbits.

PMID- 8567536
TI  - Tracheal gas exchange: perfusion-related differences in inert gas elimination.
AB  - Exchange of inert gases across the conducting airways has been demonstrated by
      using an isolated dog tracheal preparation and has been characterized by using a
      mathematical model (E. R. Swenson, H. T. Robertson, N. L. Polissar, M. E.
      Middaugh, and M. P. Hlastala, J. Appl. Physiol. 72: 1581-1588, 1992). Theory
      predicts that gas exchange is both diffusion and perfusion dependent, with gases
      with a higher blood-gas partition coefficient exchanging more efficiently. The
      present study evaluated the perfusion dependence of airway gas exchange in an in
      situ canine tracheal preparation. Eight dogs were studied under general
      anesthesia with the same isolated tracheal preparation. Tracheal perfusion (Q)
      was altered from control blood flow (Qo) by epinephrine or papaverine instilled
      into the trachea and was measured with fluorescent microspheres. Six inert gases
      of differing blood-gas partition coefficients were used to measure inert gas
      elimination. Gas exchange was quantified as excretion (E), equal to exhaled
      partial pressure divided by arterial partial pressure. Data were plotted as ln
      [E/(l-E)] vs. In (Q/Qo), and the slopes were determined by least squares.
      Excretion was a positive function of Q, and the magnitude of the response of each
      gas to changes in Q was similar and highly significant (P < or = 0.0002). These
      results confirm a substantial perfusion dependence of airway gas exchange.

PMID- 8567537
TI  - Modeling steady-state inert gas exchange in the canine trachea.
AB  - The functional dependence between tracheal gas exchange and tracheal blood flow
      has been previously reported using six inert gases (sulfur hexafluoride, ethane,
      cyclopropane, halothane, ether, and acetone) in a unidirectionally ventilated (1
      ml/s) canine trachea (J. E. Souders, S. C. George, N. L. Polissar, E. R. Swenson,
      and M. P. Hlastala. J. Appl. Physiol. 79: 918-928, 1995). To understand the
      relative contribution of perfusion-, diffusion- and ventilation-related
      resistances to airway gas exchange, a dynamic model of the bronchial circulation
      has been developed and added to the existing structure of a previously described
      model (S. C. George, A. L. Babb, and M. P. Hlastala. J. Appl. Physiol. 75: 2439
      2449, 1993). The diffusing capacity of the trachea (in ml gas.s-1.atm-1) was used
      to optimize the fit of the model to the experimental data. The experimental
      diffusing capacities as predicted by the model in a 10-cm length of trachea are
      as follows: sulfur hexafluoride, 0.000055; ethane, 0.00070; cyclopropane, 0.0046;
      halothane, 0.029; ether, 0.10; and acetone, 1.0. The diffusing capacities are
      reduced relative to an estimated diffusing capacity. The ratio of experimental to
      estimated diffusing capacity ranges from 4 to 23%. The model predicts that over
      the ventilation-to-tracheal blood flow range (10-700) attained experimentally,
      tracheal gas exchange is limited primarily by perfusion- and diffusion-related
      resistances. However, the contribution of the ventilation-related resistance
      increases with increasing gas solubility and cannot be neglected in the case of
      acetone. The increased role of diffusion in tracheal gas exchange contrasts with
      perfusion-limited alveolar exchange and is due primarily to the increased
      thickness of the bronchial mucosa.

PMID- 8567538
TI  - Regional adaptations of rabbit diaphragm muscle fibers to unilateral denervation.
AB  - We hypothesized that adaptations of the rabbit diaphragm (Dia) after unilateral
      denervation (DNV) result from removal of a neural influence rather than from
      passive stress. Length changes of midcostal and sternal Dia regions were measured
      before and after DNV by using sonomicrometry. Midcostal fibers passively
      lengthened after DNV, whereas sternal fibers shortened. In both regions, these
      length changes were associated with minimal stress, as estimated from passive
      force-length relationships. Morphological and contractile adaptions of midcostal
      and sternal Dia regions were examined after 1 and 4 wk of DNV. In both Dia
      regions, type I fibers progressively hypertrophied, whereas type IIb fibers
      atrophied. After DNV, changes in isometric contraction were similar in both Dia
      regions. Twitch contraction and half-relaxation times increased, force-frequency
      relationships shifted leftward, and maximum tetanic force decreased. We conclude
      that passive length changes and mechanical stress are not the main determinants
      of the morphological and contractile adaptations of the Dia after unilateral DNV
      but that these adaptations result from DNV itself.

PMID- 8567539
TI  - Effect of treadmill incline and speed on metabolic rate during exercise in
      thoroughbred horses.
AB  - We examined the effect of treadmill speed and incline on O2 uptake (VO2), CO2
      production, heart rate (HR), plasma lactate concentration, economy of locomotion,
      stride frequency, and stride length. A further aim was to examine the
      relationships between HR and VO2 and lactate and VO2 and whether these
      relationships vary with alterations in treadmill incline. The experiment was a
      latin square design, using five horses and five treadmill inclines (0, 2.5, 5.0,
      7.5, and 10.0%). Fit Thoroughbred horses exercised for 4 min at 3 m/s at 0%
      slope, after which the treadmill was set to the allocated incline. Speeds tested
      ranged from 1 to 13 m/s. The relationships of VO2 and CO2 production with speed
      were curvilinear at 0 and 2.5% and linear at 5, 7.5, and 10% inclines. There was
      a linear relationship of HR and speed with a significant effect of incline. The
      plasma lactate concentration increased exponentially with speed, and there was a
      significant effect of incline. Stride length increased linearly and stride
      frequency increased in a curvilinear manner with speed but there was no effect of
      incline. There were linear relationships of HR with VO2 and HR with VO2 when
      expressed as percentage of maximum VO2 and maximum HR that were not affected by
      incline. The O2 cost of exercise on a 10% incline was approximately 2.5 times
      that for exercise on the flat. The strong relationship between the percentages of
      maximum HR and maximum VO2 indicates that over a wide range of exercise
      intensities the relative VO2 can be accurately predicted from measurements of HR.

PMID- 8567540
TI  - Scaling for the VO2-to-body size relationship among children and adults.
AB  - The purpose of this study was to examine the relationship between oxygen
      consumption (VO2) and both body surface area (BSA) and body size among 30
      prepubertal children, 30 circumpubertal children, and 30 adults to determine
      which scaling model is most appropriate for making comparisons between these
      populations. All subjects participated in maximal treadmill testing and
      submaximal treadmill testing at two absolute work rates. Resting metabolic rate
      was measured on a subset of 48 subjects. It was determined that the submaximal
      VO2 (VO2 sm)-to-body size relationship provided the most appropriate model for
      comparisons. Analyses revealed a stronger linear relationship between VO2 sm and
      BSA than VO2 sm and body mass. Logarithmic transformation of the data revealed an
      allometric exponential relationship between VO2 sm and body mass. The exponent
      relating body mass to VO2 sm at 3 mph (1.34 m/s) was 0.60, whereas the exponent
      at 5 mph (2.24 m/s) was 0.75. VO2 values at 5 mph were significantly less
      variable (P < or = 0.05) than those at 3 mph. Therefore the exponent of body mass
      to the 0.75 power was considered a more appropriate basis for analysis. It was
      determined that, overall, a scaling factor of BSA or body mass to the 0.75 power
      both provide a more appropriate method of comparison than a simple ratio standard
      of body weight.

PMID- 8567541
TI  - Stable VIP analogue Ro-24-9981 potentiates substance P-induced plasma exudation
      in hamster cheek pouch.
AB  - The purpose of this study was to determine whether vasoactive intestinal peptide
      (VIP; 300 nM) and a stable cyclic analogue of VIP, Ro-24-9981 (226 nM), modulated
      neurogenic plasma exudation in the oral cavity in situ and, if so, to determine
      the mechanisms that mediated these responses. With the use of intravital
      microscopy, we found that suffusion of substance P induced a significant
      concentration-dependent formation of fluorescein-isothiocyanate-dextran (mol wt
      70 kDa) leaky sites in the hamster cheek pouch (P < 0.05). These effects were
      significantly and stereospecifically attenuated by NG-nitro-L-arginine methyl
      ester, an inhibitor of NO synthase, and restored by L-arginine, the substrate for
      NO synthase (P < 0.05). Topical application of human VIP and Ro-24-9981 had no
      significant effects of leaky site formation. In addition, human VIP had no
      significant effects on substance P-induced responses. By contrast, Ro-24-9981
      significantly potentiated substance P- and capsaicin-induced leaky site formation
      (P < 0.05). The effects of Ro-24-9981 on substance P-induced responses were
      significantly attenuated by NG-nitro-L-arginine methyl ester and restored by L
      arginine (P < 0.05). Indomethacin had no significant effects on Ro-24-9981
      induced responses. Ro-24-9981 had no significant effects on adenosine- and
      calcium ionophore A-23187-induced leaky site formation. Collectively, these data
      suggest that VIP plays no significant role in modulating neurogenic plasma
      exudation in the oral mucosa. By contrast, Ro-24-9981 amplified this response in
      a specific receptor-mediated fashion.

PMID- 8567542
TI  - Effects of muscle-to-electrode distance on the human diaphragm electromyogram.
AB  - It has been suggested that esophageal recordings of the diaphragm electromyogram
      (EMGdi) are influenced by changes in chest wall configuration. Whether the
      changes are of physiological or artifactual origin is unclear. For example, the
      distance between the esophageal electrode and the diaphragm is likely to alter
      with chest wall configuration and may lead to misinterpretations of EMGdi. The
      aims of this study were 1) to evaluate and quantify the effect of the muscle-to
      electrode (ME) distance filter on EMGdi, as obtained with a multiple-array
      esophageal electrode, 2) to take advantage of the ME distance filter to locate
      the position of the diaphragm with respect to the electrode, and 3) to evaluate
      the influence of lung volume and chest wall configuration on EMGdi center
      frequency (CF) while controlling for the ME distance filter and signal quality.
      Five subjects performed six static contractions of the diaphragm at each of seven
      chest wall configurations, as evaluated by the method of K. Konno and J. Mead (J.
      Appl. Physiol. 22: 407-422, 1967). EMGdi was measured with seven pairs of
      electrodes mounted on an esophageal catheter. The pair of electrodes whose EMGdi
      power spectra were the least filtered by the ME distance was assumed to be
      closest to the diaphragm. The results of the study indicated that 1) EMGdi power
      spectra were strongly affected by the distance between the diaphragm and the
      electrodes. CF decreased by approximately 1 Hz/mm displacement away from the
      electrode pair closest to the diaphragm; and 2) no systematic relationship was
      found between changes in chest wall configuration and CF, when CF was measured
      from the electrode pair closest to the diaphragm. We conclude that the EMGdi CF
      can be reliably measured with a multiple-array esophageal electrode that covers
      the span of diaphragmatic excursion and by selecting the pair of electrodes that
      is the closest to the diaphragm.

PMID- 8567543
TI  - Temporal heterogeneity of regional pulmonary perfusion is spatially clustered.
AB  - This study investigates temporal changes in regional pulmonary perfusion. Five
      dogs were studied with five or six different radiolabeled microspheres being
      injected via a central vein over 30 s every 20 min. The lungs of each animal were
      cubed into 1.9 cm3 pieces with spatial coordinates noted for each piece. Within
      individual pieces, the coefficient of variation of regional perfusion over time
      was 17.2 +/- 6.8% (SD) and across dogs accounted for 7.26 +/- 5.7% of total
      perfusion heterogeneity. Temporal variability or "twinkling" was not random. When
      lung pieces with similar temporal flow patterns were grouped together (regardless
      of spatial location), groups were more tightly clustered in space than expected
      by chance. Statistical clustering methods revealed regulation of blood flow on a
      large scale (lobar arteries), and fractal analyses suggested regulation existed
      on a smaller scale (arterioles). We conclude that regional pulmonary perfusion is
      heterogeneous over time in a nonrandom pattern and that pieces clustered by
      temporal patterns of perfusion are neighbors in the spatial domain.

PMID- 8567544
TI  - "Ventilatory stability to CO2 disturbances in wakefulness and quiet sleep".

PMID- 8567545
TI  - Ventilatory stability to CO2 disturbances in wakefulness and quiet sleep.
AB  - Oscillatory ventilatory pattern occurs more frequently in sleep despite the
      stabilizing factor of sleep-induced reduction in CO2 chemosensitivity. In nine
      young normal humans, we have tested the hypothesis that, despite a sleep-induced
      reduction in chemosensitivity, the transient central chemoreceptor-mediated
      change inspiratory ventilation (VI) caused by a standardized disturbance to
      chemoreflex ventilatory control is similar in quiet sleep and wakefulness. The
      equivalent VI response to a single-breath hyperoxic hypercapnic stimulus (i.e.,
      inhaling a single breath of 0.01 liter of CO2 in O2--a direct measure of "closed
      loop" dynamic response) was determined using pseudorandom binary CO2 stimulation
      and the prediction-error method of transfer function estimation. From these data,
      the response of VI to a single-breath increase of 1 Torr in end-tidal PCO2 was
      also derived, from which "dynamic" central chemosensitivity was calculated.
      Despite a 43% reduction in dynamic central chemosensitivity, the peak and the
      area under the closed-loop VI response are similar in wakefulness and quiet
      sleep, whereas sleep increases the duration of the response by 48%. Thus
      hyperoxic ventilatory stability is not reduced in quiet sleep relative to
      wakefulness. We propose that changes in dynamics of pulmonary gas exchange in
      sleep substantially offset the decreased chemosensitivity, thereby maintaining
      the gains and time constants of the central chemoreceptor-mediated component of
      the closed-loop ventilatory control system similar to those during wakefulness.

PMID- 8567546
TI  - Capsazepine inhibits cough induced by capsaicin and citric acid but not by
      hypertonic saline in guinea pigs.
AB  - Acidic solutions mimick many of the effects of capsaicin (Cap), including pain,
      bronchoconstriction, cough, and sensory neuropeptide release. Evidence from the
      use of the Cap antagonist capsazepine suggests that in some cases protons act at
      the Cap receptor. In the present study, we have investigated whether cough evoked
      by Cap and citric acid (CA) is mediated specifically via the Cap receptor on
      airway sensory nerves. We have examined the effects of capsazepine on Cap-, CA-,
      and hypertonic saline-induced cough and also on CA-induced nasal irritation in
      awake guinea pigs. Capsazepine was nebulized for 5 min before cough challenges
      with Cap for 5 min and CA for 10 min. Control animals were pretreated with
      vehicle alone. Capsazepine (100 microM) inhibited the cough response to 30 microM
      Cap from 0.77 +/- 0.14 coughs/min in control animals to 0.23 +/- 0.08 coughs/min
      (P < 0.05) and to 80 microM Cap from 1.4 +/- 0.23 to 0.3 +/- 0.11 coughs/min (P <
      0.01). There was no effect, however, of lower concentrations of capsazepine (5
      and 10 microM) against Cap-evoked cough. At a concentration of 100 microM,
      capsazepine also inhibited the coughing induced by 0.25 M CA from 1.8 +/- 0.26 to
      0.93 +/- 0.31 coughs/min (P < 0.05) but not that induced by 0.5 M CA. Nasal
      irritation induced by 0.25 M CA, but not by 0.5 M CA, was also inhibited by
      capsazepine from 2.47 +/- 0.37 to 0.75 +/- 0.31 nose wipes/min (P < 0.05). This
      inhibitory effect of capsazepine did not appear to reflect a nonspecific
      suppression of the cough reflex, since cough evoked by exposure to hypertonic
      (7%) saline for 10 min was unaffected by pretreatment with capsazepine (100
      microM). These data show that capsazepine is a specific inhibitor of Cap- and CA
      induced cough in guinea pigs. Moreover, they suggest that low pH stimuli evoke
      cough and nasal irritation by an action at the Cap receptor, either directly or
      through the release of an intermediate agent.

PMID- 8567547
TI  - Inhaled nitric oxide does not alter endotoxin-induced nitric oxide synthase
      activity during rat lung perfusion.
AB  - Nitric oxide (NO) has been demonstrated to decrease its own synthesis in tissue
      preparations. We tested the hypothesis that endogenous NO synthesis induced by
      lipopolysaccharides (LPS) would be decreased by exogenous NO during isolated lung
      perfusion. Rats were pretreated with either saline or LPS 48 h before lung
      harvest. Endogenous NO synthase activity was measured as conversion of L-[14C]
      arginine to L-[14C]citrulline during 90 min of perfusion. NO (100 ppm) was added
      to the ventilating gas during perfusion of lungs from one group of control or LPS
      treated rats. A second group of control or LPS-treated rats was exposed
      chronically to 100 ppm NO for the 48 h before lung harvest, in addition to
      receiving 100 ppm NO added to the ventilating gas during lung perfusion. We
      conclude that conversion of L-[14C]arginine to L-[14C]citrulline was minimal in
      control lungs and increased in response to LPS pretreatment. NO added to the
      ventilating gas for the 90 min of ex vivo perfusion did not alter the rate of L
      [14C]citrulline production. In vivo exposure to 100 ppm NO for 48 h did not alter
      the induction of inducible NO synthase activity as measured during ex vivo lung
      perfusion. This indicates that inhaled NO does not exert negative-feedback
      inhibition on inducible NO synthase in the ex vivo rat lung.

PMID- 8567548
TI  - Effect of periodic thermal stimulus on heart rate in term newborn infant.
AB  - We studied heart rate changes in 25 term infants aged 1-7 days in quiet sleep
      during periodic thermal stimulation of one foot to widen the range of frequencies
      previously studied by others and to develop spectral analysis methods to quantify
      responses to thermal and other periodic sensory stimuli. The stimulation
      frequency was 0.10 Hz in all babies and ranged from 0.05 to 0.15 Hz in some. At
      0.10 Hz, there was 1) an increase in spectral power at the frequency of
      stimulation (P < 0.001), 2) a tendency for overall low-frequency power to
      increase, 3) a reduction in respiratory sinus arrhythmia (P < 0.025), and 4)
      attenuation in the response between the first and second minute of stimulation (P
      < 0.01). At other frequencies of stimulation, essentially similar results were
      obtained. Respiration and other types of periodic sensory stimulation may also
      entrain the heart rate; we raise the question of whether low-frequency
      oscillations in heart rate are in fact related to thermoregulation or are a
      nonspecific feature of integrative processes in the brain stem.

PMID- 8567549
TI  - Pancreatic islet insulin secretion is increased after resistance exercise in
      rats.
AB  - The purpose of this study was to determine whether 4 days of resistance exercise
      facilitated insulin secretory adaptations at the level of the pancreatic islets.
      Eighteen male 400-g Sprague-Dawley rats were randomly assigned to two groups. All
      animals were operantly conditioned to engage in a resistance exercise protocol
      that required full extension of the hindlimbs. Resistance was applied to the
      animals via a leather-and-Velcro vest to which weighted pouches were attached.
      The acute (Acute, n = 9) group engaged in four exercise sessions (50 reps each)
      with increased resistance for each session (70-->120-->120-->190 g). Sessions
      were separated by 48 h of rest. The nonexercised (Nonex, n = 9) group engaged in
      the same protocol without resistance. Islets were dispersed 16 h postexercise,
      incubated for 48 h, and perifused (17-20 islets/rat) with a medium containing 10
      mM L-arginine or 16 mM glucose as the insulin secretagogue. Basal insulin
      secretion from the islets before the introduction of L-arginine or 16 mM glucose
      was the same for the Acute and Nonex groups (P > 0.05). The total insulin
      response to 10 mM arginine was significantly higher for the Acute than for the
      Nonex group (1.16 +/- 0.30 and 0.31 +/- 0.10 ng insulin.islet-1.25 min-1,
      respectively, P < 0.05). There were no differences between groups for the overall
      insulin response to glucose (P > 0.05). However, the late-phase insulin response
      to glucose was higher for the Acute group (P < 0.05). These data suggest that
      insulin secretory adaptations occur at the level of the pancreatic islets after 4
      days of resistance exercise.

PMID- 8567550
TI  - Endothelin-1 potentiates leukotoxin-induced edematous lung injury.
AB  - We tested the hypothesis that leukotoxin (Lx), a cytochrome P-450-dependent
      linoleate product of leukocytes, can stimulate the release of endothelin-1 (ET-1)
      from the lung and further that exogenous ET-1 synergizes with Lx to produce
      edematous lung injury. In isolated rat lungs perfused with Earle's balanced salt
      solution, Lx (10 mumol) alone caused lung edema and increased the perfusate and
      lung tissue ET-1 levels. The combination of ET-1 (5 nM) and Lx (5 mumol), at
      concentrations that by themselves did not increase wet lung weight, significantly
      increased wet lung weight, wet-to-dry lung weight ratio, as well as the lung
      effluent lactate dehydrogenase activity. Pretreatment with BQ-123 (5 x 10(-6) M),
      an endothelin A receptor antagonist that significantly attenuated the ET-1 (5 nM)
      induced increase in pulmonary arterial pressure (Ppa) and pulmonary capillary
      pressure (Ppc), suppressed the edematous lung injury generated by the combination
      of ET-1 and Lx, suggesting that the edema-enhancing effect of ET-1 in Lx-treated
      lungs occurred through endothelin A receptor-dependent elevation of Ppa and Ppc.
      Elevation of the pulmonary venous pressure in Lx-treated lungs (13.5 cmH2O)
      mimicked the effect of ET-1 on Ppa and Ppc and produced a degree of lung edema
      that was comparable to that after combined ET-1 + Lx treatment but without
      increase in the perfusate lactate dehydrogenase. These data support the idea that
      ET-1 and Lx promote lung edema in a synergistic fashion.

PMID- 8567551
TI  - Age alters regional distribution of blood flow during moderate-intensity
      exercise.
AB  - During dynamic exercise in warm environments, requisite increases in skin and
      active muscle blood flows are supported by increasing cardiac output (Qc) and
      redistributing flow away from splanchnic and renal circulations. To examine the
      effect of age on these responses, six young (Y; 26 +/- 2 yr) and six older (O; 64
      +/- 2 yr) men performed upright cycle exercise at 35 and 60% of peak O2
      consumption (VO2peak) in 22 and 36 degrees C environments. To further isolate
      age, the two age groups were closely matched for VO2peak, weight, surface area,
      and body composition. Measurements included heart rate, Qc (CO2 rebreathing),
      skin blood flow (from increases in forearm blood flow (venous occlusion
      plethysmography), splanchnic blood flow (indocyanine green dilution), renal blood
      flow (p-amino-hippurate clearance), and plasma norepinephrine concentration.
      There were no significant age differences in Qc; however, in both environments
      the O group maintained Qc at a higher stroke volume and lower heart rate. At 60%
      VO2peak, forearm blood flow was significantly lower in the O subjects in each
      environment. Splanchnic blood flow fell (by 12-14% in both groups) at the lower
      intensity, then decreased to a greater extent at 60% VO2peak in Y than in O
      subjects (e.g., -45 +/- 2 vs. -33 +/- 3% for the hot environment, P < 0.01).
      Renal blood flow was lower at rest in the O group, remained relatively constant
      at 35% VO2peak, then decreased by 20-25% in both groups at 60% VO2peak. At 60%
      VO2peak, 27 and 37% more total blood flow was redistributed away from these two
      circulations in the Y than in the O group at 22 and 36 degrees, respectively. It
      was concluded that the greater increase in skin blood flow in Y subjects is
      partially supported by a greater redistribution of blood flow away from
      splanchnic and renal vascular beds.

PMID- 8567552
TI  - Effect of carotid chemoreceptor denervation on breathing during ventrolateral
      medullary cooling in goats.
AB  - It has been postulated that the so-called area S of the ventrolateral medulla
      (VLM) integrates peripheral chemoreceptor activity; thus cooling-induced
      dysfunction of neurons in this VLM area should functionally eliminate carotid
      chemoreceptor stimulation of breathing. Accordingly, carotid chemoreceptor
      denervation (CBD) should not alter the breathing effects of VLM neuronal
      dysfunction. To test this hypothesis in awake goats, chronically implanted
      thermodes were used to cool the VLM and thereby cause reversible neuronal
      dysfunction in all or portions of VLM areas M and S. Within 5 s after initiation
      of cooling approximately 60-100% of areas M and S in (P < 0.05) uniformly over
      conditions of eupnea, hypercapnia, and hypoxia. Between 10 and 20 s of cooling,
      the reduction in VI was approximately 10% greater (P < 0.05) during hypercapnia
      than during eupnea and hypoxia. For the remaining 10 s of cooling and for
      approximately 1 min after cooling, VI increased to and above control for all
      conditions. For all conditions, CBD accentuated the depression of VI during
      cooling, causing VI to decrease (P < 0.05) 10-40% more than before CBD. After
      CBD, the greatest effect on VI of cooling was again during hypercapnia. Thus the
      carotid bodies in intact goats appear to sense blood gas errors caused during VLM
      cooling to minimize the decreases in VI. We conclude that the data from this
      study do not support the concept that the VLM integrates carotid chemoreceptor
      activity.

PMID- 8567553
TI  - Effect of T-kinin on microvascular permeability and its modulation by peptidases
      in rat airways.
AB  - T-kinin (Ile-Ser-bradykinin), the product of T-kininogen, has been found in rat
      plasma during systemic inflammation, but the effect of this kinin on airway
      inflammatory response is unknown. We examined the effect of T-kinin on vascular
      permeability in airways of anesthetized rats in vivo by using photometric
      measurement of the extravasated Evans blue. Intravenous injection of T-kinin (0.1
      10 mumol/kg) increased dye extravasation in a dose-dependent manner, with 134%
      for trachea and 117% for bronchi by 1 mumol/kg. Pretreatment with bradykinin B2
      receptor antagonist Hoe-140 (100 nmol/kg), but not the B1-receptor antagonist des
      Arg9-Leu8-bradykinin (5 mg/kg), abolished plasma extravasation evoked by T-kinin
      (1 mumol/kg). NK1 tachykinin-receptor antagonist CP-99994 (4 mg/kg) did not
      affect T-kinin-induced vascular leakage. Pretreatment with captopril (2.5 mg/kg),
      angiotensin-converting enzyme inhibitor, potentiated T-kinin (100 nmol/kg)
      induced plasma extravasation, whereas phosphoramidon (2.5 mg/kg), a neutral
      endopeptidase inhibitor, had no effect. We conclude that T-kinin produces airway
      vascular extravasation via stimulation of B2 receptors. The effect is modulated
      by endogenous angiotensin-converting enzyme and is not mediated via activation of
      sensory nerve.

PMID- 8567554
TI  - Gas exchange, blood lactate, and plasma catecholamines during incremental
      exercise in hypoxia and normoxia.
AB  - The interrelationships among blood lactate (La-) and plasma norepinephrine (NE)
      and epinephrine (Epi) were studied simultaneously with measures of ventilation
      (VE) and gas exchange during incremental exercise to exhaustion in nine healthy
      young men. We wanted to observe whether the tight coupling that exists during
      normoxic exercise between the concentrations of La- ([La-]) and of both NE and
      Epi would also be found in hypoxia (inspired O2 fraction = 0.14). In addition, we
      used recently advocated methods of V slope [CO2 output vs. O2 uptake (VO2)] to
      select the ventilatory threshold (VT) and log-log transformation of [La-] and VO2
      to select the lactate threshold (LT). Peak VO2 was reduced from 4,164 +/- 184
      ml/min in normoxia to 3,635 +/- 144 ml/min in hypoxia (P < 0.05). The increase in
      [La-] was linearly related to the increases in both NE and Epi concentrations in
      the normoxic and hypoxic tests (r = 0.92-0.96). Estimates of VO2 at VT were
      significantly greater than those at LT in both normoxia and hypoxia, but these
      estimates were poorly correlated (r = -0.11-0.46). VT and LT were reduced by
      hypoxia. Visual interpretation of the VT by examination of VE vs. VO2 and VE/VO2
      vs. VO2 did not differ from the LT, but they were less than the VTs by the V
      slope method (P < 0.05); yet, all were poorly correlated. The tight coupling
      between the increase in [La-] and the increase in plasma catecholamines might
      indicate a common mechanism for the increase or a causative link. VT and LT
      provided estimates of the general trend in the data, but the poor correlation
      between them questions the utility of attempting to predict one from the other.

PMID- 8567555
TI  - Effect of capillary pressure and lung distension on capillary recruitment.
AB  - To investigate the effect of capillary pressure and alveolar distension on
      capillary recruitment, we used video-microscopy to quantify capillary recruitment
      in individual subpleural alveolar walls. Canine lobes were perfused with
      autologous blood either while inflated by positive airway pressure or while
      inflated by negative intrapleural pressure in the intact thorax with airway
      pressure remaining atmospheric. Low flow rates minimized the arteriovenous
      pressure gradient (< 5 mmHg), permitting capillary pressure estimation by
      averaging these pressures. Capillary pressure was varied stepwise from airway
      pressure to 30 mmHg above airway pressure. Capillary recruitment always began as
      capillary pressure exceeded airway pressure. At low positive airway pressures,
      the capillaries of the excised lobes opened suddenly over a narrow pressure
      range. AT higher airway pressures and in the intact thorax, recruitment occurred
      over a wide range of capillary pressures. We conclude that capillary perfusion
      begins when intracapillary pressure just exceeds alveolar pressure but that
      further increases in capillary pressure recruit capillaries depending on tension
      in the alveolar wall, whether imposed by positive airway pressure or by gravity
      when the lung is suspended in an intact thorax.

PMID- 8567556
TI  - Myoglobin saturation in free-diving Weddell seals.
AB  - Although the consumption of myoglobin-bound O2 (MbO2) stores in seal muscles has
      been demonstrated in seal muscles during laboratory simulations of diving, this
      may not be a feature of normal field diving in which measurements of heart rate
      and lactate production show marked differences from the profound diving response
      induced by forced immersion. To evaluate the consumption of muscle MbO2 stores
      during unrestrained diving, we developed a submersible dual-wavelength laser near
      infrared spectrophotometer capable of measuring MbO2 saturation in swimming
      muscle. The probe was implanted on the surface of the latissimus dorsi of five
      subadult male Weddell seals (Leptonychotes weddelli) released into a captive
      breathing hole near Ross Island, Antarctica. Four seals had a monotonic decline
      of muscle O2 saturation during free diving to depths up to 300 m with median
      slopes of -5.12 +/- 4.37 and -2.54 +/- 1.95%/min for dives lasting < 17 and > 17
      min, respectively. There was no correlation between the power consumed by
      swimming and the desaturation rate. Two seals had occasional partial muscle
      resaturations late in dives, indicating transfer of O2 from circulating blood to
      muscle myoglobin. Weddell seals partially consume their MbO2 stores during
      unrestrained free diving.

PMID- 8567557
TI  - Pulmonary vascular impedance response to hypoxia in dogs and minipigs: effects of
      inhaled nitric oxide.
AB  - The pig has been reported to present with a stronger hypoxic pulmonary
      vasoconstriction (HPV) than many other species, including dogs. We investigated
      [pulmonary arterial pressure (Ppa)-pulmonary arterial occluded pressure (Ppao)]
      vs. pulmonary blood flow (Q) relationships and pulmonary vascular impedance (PVZ)
      spectra in nine minipigs and nine weight-matched dogs. The animals were
      anesthetized and ventilated in hyperoxia [inspired O2 fraction 0.4] or hypoxia
      (inspired O2 fraction 0.12). PVZ was computed from the Fourier series for Ppa and
      Q. In hyperoxia, the pigs had a higher Ppa (26 +/- 1 vs. 16 +/- 1 mmHg), a higher
      first-harmonic impedance (Z1), and a more negative low-frequency phase angle but
      no different characteristic impedance (Zc) compared with the dogs at the same Q.
      Hypoxia in the dogs increased (Ppa-Ppao) at all levels of Q studied by an average
      of 2 mmHg but did not affect Z1 or Zc. Hypoxia in the pigs increased (Ppa-Ppao)
      at all levels of Q by an average of 13 mmHg and increased Z1 and Zc. Inhaled NO
      (150 ppm) reversed the hypoxia-induced changes in (Ppa-Ppao)/Q plots and PVZ in
      the dogs and pigs. However, differences in (Ppa-Ppao)/Q plots and PVZ between the
      dogs and pigs in hyperoxia and hypoxia were not affected by inhaled NO. We
      conclude 1) that minipigs present with an elevated pulmonary vascular resistance
      and impedance in hypoxia more than in hyperoxia and 2) that baseline differences
      in pulmonary hemodynamics between dogs and minipigs are structural rather than
      functional.

PMID- 8567558
TI  - Secretory leukoprotease inhibitor attenuates lung injury induced by continuous
      air embolization into sheep.
AB  - Continuous air embolization (CAE) into the pulmonary arterial circulation of
      sheep results in functional and structural changes of chronic pulmonary
      hypertension. Release of elastin peptides into lung lymph during CAE and
      attenuation of CAE-induced pulmonary hypertension by neutrophil depletion suggest
      that neutrophil elastase may contribute to these changes. To investigate this
      notion, we treated awake sheep with a potent neutrophil elastase inhibitor,
      recombinant secretory leukoprotease inhibitor (SLPI) (100 mg/day by aerosol),
      during 12 days of CAE (CAE+SLPI; n = 7). Controls included sheep receiving CAE +
      vehicle (VEH) (n = 6), VEH alone (n = 3), and SLPI alone (n = 3). SLPI
      significantly attenuated the CAE-induced increases in lung lymph flow (day 8; 2.3
      +/- 0.5 vs. 5.6 +/- 1.7 ml/15 min), protein clearance (day 8; 1.36 +/- 0.32 vs.
      3.08 +/- 0.84 ml/15 min), and elastin peptide concentration (day 8; 243 +/- 41
      vs. 398 +/- 44 ng/ml). SLPI delayed the onset of sustained pulmonary hypertension
      from day 8 to day 12. Both CAE groups showed similar structural changes in the
      pulmonary arteries. SLPI was well tolerated in control sheep and did not affect
      hemodynamics or structure. We conclude that serine proteases may contribute to
      the early initiation of chronic pulmonary hypertension but do not play a striking
      role in its eventual development.

PMID- 8567559
TI  - Glibenclamide does not reverse attenuated vasoreactivity to acute or chronic
      hypoxia.
AB  - Recent studies from our laboratory have shown that acute and chronic hypoxic
      exposures are associated with attenuated systemic vasoreactivity in conscious
      rats. The present studies examined the role of adenosine triphosphate-sensitive
      potassium channels (KATP channels) in modulating the pressor and vasoconstrictor
      responses to phenylephrine (PE) in conscious instrumented rats 1) during acute
      hypoxia or 2) after chronic hypoxic exposure. Mean arterial pressure, mean
      cardiac output, and total peripheral resistance were assessed before and after
      graded infusions of PE in both groups of rats under normoxic or hypoxic
      conditions. Additionally, the role of KATP channels in attenuating vasoreactivity
      was determined by administration of glibenclamide (KATP channel blocker) before
      PE infusions. Acute hypoxia (12% O2) was associated with reduced pressor and
      constrictor responses to PE in control animals. Furthermore, acute return to room
      air did not restore the pressor and constrictor responses in the chronically
      hypoxic rats. Glibenclamide infusion did not influence the pressor or
      vasoconstrictor responses to PE in either group of animals during normoxia or
      acute hypoxia. Therefore, our data suggest that opening of KATP channels is not
      involved in the attenuated vasoreactivity associated with acute and chronic
      hypoxia in the conscious rat.

PMID- 8567560
TI  - Hypoxic respiratory responses attenuated by ablation of the cerebellum or
      fastigial nuclei.
AB  - The general contribution of the cerebellum to hypoxic respiratory responses and
      the special role of the fastigial nucleus (FN) in the hypoxic respiratory reflex
      mediated via peripheral chemoreceptors were investigated in anesthetized and
      spontaneously breathing cats. Seven cats were exposed to isocapnic progressive
      hypoxia before and after cerebellectomy by decreasing the fractional
      concentration of end-tidal O2 (FETO2) from 15 +/- 0.3% to 7% while maintaining
      the pressure of end-tidal CO2 at a constant level of approximately 30 mmHg. Five
      additional cats inhaled five breaths of pure N2 (transient hypoxia) and received
      sodium cyanide (50 micrograms iv) before and after thermal lesions of the
      bilateral FN. The results showed that cerebellectomy or FN lesions failed to
      alter the respiratory variables (minute ventilation, tidal volume, respiratory
      frequency, and the peak of integrated diaphragm activity) during eupneic
      breathing. However, cerebellectomy significantly attenuated minute ventilation
      (FETO2 < or = 13%) and the peak of integrated diaphragm activity (FETO2 < or =
      10%) compared with control. During progressive hypoxia, changes in respiratory
      frequency were noted earlier (FETO2 < or = 13%) than changes in tidal volume
      (FETO2 < or = 10%). Similarly, bilateral lesions of the FN resulted in a profound
      reduction in these respiratory responses to transient hypoxia and sodium cyanide.
      We conclude that the cerebellum can facilitate the respiratory response to
      hypoxia and that the FN is an important region in the modulation of the hypoxic
      respiratory responses, presumably via its effects on inputs from peripheral
      chemoreceptors.

PMID- 8567561
TI  - Maximal airway response in mature and immature rabbits during tidal ventilation.
AB  - Airway closure during maximal methacholine (MCh) challenge was evaluated using
      alveolar capsules in eight immature and eight mature anesthetized rabbits in vivo
      during imposed tidal ventilation. Changes in airway opening and alveolar
      pressures (delta PA) and pulmonary resistance (RL) were measured during MCh
      challenge at a positive end-expiratory pressure of 5 cmH2O. In immature rabbits,
      delta PA remained > 3 cmH2O in all animals, indicating no detectable airway
      closure. This contrasts to our previous study of isolated immature rabbit lungs
      under static conditions in which delta PA was < 0.1 cmH2O during maximal MCh
      challenge, findings consistent with airway closure. Airway closure also did not
      occur in mature animals during tidal ventilation in vivo; however, the frequency
      of closure in isolated lungs under static conditions was very low. With
      increasing MCh, end-expiratory PA increased in immature but not in mature
      rabbits. RL did not reach a plateau in immature rabbits during MCh, whereas a
      plateau was reached in mature rabbits. Immature rabbits also had greater
      increases in RL. These results suggest that tidal ventilation can limit
      bronchoconstriction in immature rabbits and prevent airway closure during maximal
      MCh challenge. Tidal ventilation may limit bronchoconstriction by inhibitory
      effects of stretch on airway smooth muscle contraction and also by causing
      hyperinflation and thereby increasing transpulmonary pressure.

PMID- 8567562
TI  - Effects of posture on respiratory mechanics in obesity.
AB  - Increased abdominal mass in obesity should enhance normal gravitational effects
      on supine respiratory mechanics. We have examined respiratory impedance (forced
      oscillation over 4-26 Hz applied at the mouth during tidal breathing), maximum
      inspiratory and expiratory mouth pressures (MIP and MEP), and maximum effort flow
      volume curves seated and supine in seven obese subjects (O) (mean age 51 yr, body
      mass index 43.6 kg/m2) and seven control subjects (C) (mean age 50 yr, body mass
      index 21.8 kg/m2). Seated mean total lung capacity was smaller in O than in C (82
      vs. 100% of predicted); ratio of functional residual capacity (FRC) to total lung
      capacity averaged 43% in O and 61% in C (P < 0.01). Total respiratory resistance
      (Rrs) at 6 Hz seated was higher in O (4.6 cmH2O.l-1.s) than in C (2.2 cmH2O.l
      1.s; P < 0.001); total respiratory reactance (Xrs) at 6 Hz was lower in O than in
      C. In C, on changing to the supine posture, mean Rrs at 6 Hz rose to 2.9 cmH2O.l
      1.s, FRC fell by 0.68 liter, and Xrs at 6 Hz showed a small fall. In O, despite
      no further fall in FRC, supine Rrs at 6 Hz increased to 7.3 cmH2O.l-1.s, and
      marked frequency dependency of Rrs and falls in Xrs developed. Seated, MIP and
      MEP in C and O were similar; supine there were small falls in MEP and maximum
      expiratory flow in O. The site and mechanism of the increase in supine Rrs and
      reduction in supine Xrs and the mechanism maintaining supine FRC in obesity all
      need further investigation.

PMID- 8567563
TI  - Effect of graded epinephrine infusion on blood lactate response to exercise.
AB  - In an attempt to determine whether the lactate threshold (LT) is the result of a
      sudden increase in plasma epinephrine (Epi), eight healthy college-aged males
      (22.4 +/- 0.4 yr) were recruited to perform three cycle ergometer exercise tests.
      Each subject performed a graded exercise test (GXT) to determine LT, Epi
      threshold, and norepinephrine threshold (64.6 +/- 2.4, 62.5 +/- 2.4, and 60.8 +/-
      4.3% peak oxygen uptake, respectively). Each subject also completed, in random
      order, two 30-min submaximal (20% peak oxygen uptake below LT) exercise tests.
      During one test, graded Epi infusions were carried out at rates of 0.02-0.12
      micrograms.kg-1.min-1; the other served as a control test. Infusion resulted in
      plasma Epi concentrations similar to those observed during GXT. The increase in
      blood lactate with Epi infusion was significantly greater than that during the
      control test (3.0 +/- 0.3 vs. 1.4 +/- 0.1 mmol/l at minute 30) but did not
      approach levels exhibited during GXT. We suggest an interaction of the increasing
      plasma Epi with other factors may be responsible for the sudden increase in blood
      lactate during graded exercise.

PMID- 8567564
TI  - Pulmonary vasodilator drugs decrease lung liquid production in fetal sheep.
AB  - To examine a potential relationship between pulmonary vasodilatation and fetal
      lung liquid production, I measured lung liquid production in 20 fetal sheep at
      130 +/- 4 days gestation while using several agents known to increase pulmonary
      blood flow. Thirty-two studies were done in which left pulmonary arterial flow
      (Qlpa) was measured by an ultrasonic Doppler flow probe and net lung luminal
      liquid production (Jv) was measured by plotting the change in lung luminal liquid
      concentration of radiolabeled albumin, an impermeant tracer that was mixed into
      the lung liquid at the start of each study. Qlpa and Jv were measured during a 1-
      to 2-h baseline period and then during a 1- to 2-h infusion period in which the
      fetuses received either an intravenous infusion of acetylcholine (n = 8),
      prostaglandin D2 (n = 10), or the leukotriene blocker FPL-55712 (n = 7). These
      vasodilators work by different mechanisms, each mechanism having been implicated
      in the decrease in pulmonary vascular resistance seen at birth. Control (saline)
      infusions (n = 7) caused no change in either Qlpa or Jv over 4 h. All vasodilator
      agents significantly increased pulmonary blood flow and decreased Jv. Pulmonary
      arterial pressure did not change significantly in either the control,
      acetylcholine, prostaglandin, or leukotriene-blocker studies, indicating that
      pulmonary vascular resistance decreased. Thus agents that increase pulmonary
      blood flow by mechanisms that occur at birth also decrease lung liquid production
      in fetal lambs.

PMID- 8567565
TI  - Effects of physical conditioning on endogenous nitric oxide output during
      exercise.
AB  - Nitric oxide (NO) has been detected in the expiratory air of normal animals and
      human subjects. Recent experiments revealed that expiratory NO production rises
      during exercise and correlates well with O2 consumption (VO2) and heart rate.
      Whether physical conditioning influences expiratory NO output production remains
      unclear. In this study, NO concentration in expired gas was measured in 18
      healthy male volunteers subdivided into three groups (sedentary, intermediate,
      and athletic) on the basis of the subjects' state of physical conditioning.
      Measurements were taken at rest and during two steady-state exercise bouts on a
      bicycle ergometer designed to elicit VO2 of 1 and 2 l/min with the athletes
      performing an additional bout at VO2 of 4 l/min. In the sedentary and
      intermediate groups, expired NO concentrations declined significantly with
      increasing VO2. In contrast, expired NO levels declined only slightly with
      increasing VO2 in the athletes. At a VO2 of 2 l/min, expired NO concentrations
      were significantly higher in the athletes compared with values in the other
      groups. When correlated with minute ventilation (VE), expired NO concentrations
      declined linearly with the increase in VE in sedentary and intermediate groups
      but not in the athletes. Only the athletes had a significant linear increase in
      NO output (expired NO x VE) with increasing VO2 (P < 0.001). These results
      support the notion that physical conditioning increases expiratory NO output
      during exercise. We speculate that the rise in expiratory NO output in the
      athletes might be due to increased vascular and/or epithelial production of NO.
      Enhanced vascular NO production may be the result of increased shear stress
      and/or upregulation of endothelial NO synthase gene expression.

PMID- 8567566
TI  - Computerized tomography and pulmonary diffusing capacity in highly trained
      athletes after performing a triathlon.
AB  - We investigated the computerized tomographies (CTs) of the thorax and the
      pulmonary diffusing capacity for CO (DLCO) in eight male athletes before and
      after a triathlon. DLCO and alveolar volume (VA) were simultaneously measured
      during 9 s of breath holding. The transfer coefficient (KCO = DLCO/VA) was then
      calculated. CT scanning was performed during breath holding with the subjects in
      the supine position. Scanner analysis was done by 1) counting the linear and
      polygonal opacities (index of interstitial fluid accumulation) and 2) calculating
      the physical mean lung density and the mean slice mass. Results showed a
      significant reduction in DLCO (44.9 +/- 2.3 vs. 42.9 +/- 1.7 ml.min-1.mmHg-1; P <
      0.05) and KCO (6.0 +/- 0.3 vs. 5.6 +/- 0.3 ml.min-1.mmHg-1.l of VA-1; P < 0.05)
      after the triathlon and an increase in mean lung density (0.21 +/- 0.009  vs.
      0.25 +/- 0.01 g/cm3; P < 0.0001). The number of polygonal and linear opacities
      increased after the race (P < 0.001). This study confirmed that DLCO and KCO
      decrease in elite athletes after a long-distance race and showed a concomitant
      increase in CT lung density and in the number of opacities.

PMID- 8567567
TI  - Vagal neuroeffector mechanisms affecting transpulmonary pressure in the intact
      rat.
AB  - Experiments were conducted with chloralose-urethan anesthetized rats to assess
      the effects of 1) bilateral stimulation of the cervical vagus nerves and 2)
      parasympathomimetic and sympathomimetic agents. Transpulmonary pressure (Ptp) was
      used as an index of airway smooth muscle tone, and peak inspiratory Ptp (Ptppeak)
      values were used for a comparison of responses. In untreated animals, vagal
      stimulation elicited an increase in Ptppeak of 155%. Cooling of the vagus nerves
      to 15 degrees C abolished the response of Ptppeak to vagal stimulation. Although
      isoproterenol (1-10 micrograms/kg i.v.) did not alter resting Ptppeak, it did
      prevent vagal stimulation from evoking an increase in Ptppeak. Nadolol (1.5 mg/kg
      i.v.) augmented the increase in Ptppeak elicited by vagal stimulation. Vagal
      stimulation did not evoke any change in Ptppeak after the administration of both
      nadolol and atropine or after combined administration of nadolol, atropine, and
      either serotonin aerosol or prostaglandin F2 alpha. In rats pretreated with
      capsaicin 1 wk before the experiment, vagal stimulation evoked an increase in
      Ptppeak that was not statistically different from that of untreated control
      animals. Therefore, nonadrenergic noncholinergic systems did not appear to play
      an independent role in the response of the airways to the activation of the vagus
      nerves.

PMID- 8567568
TI  - Airway edema potentiates airway reactivity.
AB  - Thickening of the airway wall has been hypothesized to be one of the mechanisms
      contributing to airway hyperresponsiveness in asthma. If such thickening of the
      wall is internal to the airway smooth muscle or otherwise causes a decrease in
      baseline airway caliber, it should also cause exaggerated airway responsiveness.
      In the present study, we used high-resolution computed tomography to directly
      measure the changes in the caliber and wall thickness of conducting airways after
      aerosol histamine challenge before and after normal saline volume loading. On
      separate days, five anesthetized dogs received either a baseline aerosol
      challenge of 3 mg/ml of histamine for five breaths or the same aerosol challenge
      immediately after a 100 ml/kg bolus of normal saline infused over a 10-min
      period. Baseline aerosol histamine challenge decreased airway area to 71 +/- 2%
      (SE) of the control value (P < 0.05). Intravenous administration of 100 ml/kg of
      normal saline increased wall area by decreasing airway luminal area to 78 +/- 3%
      of the control value (P < 0.01), with no change in outer airway area. Aerosol
      histamine challenge superimposed on this engorgement with normal saline challenge
      further decreased airway luminal area to 54 +/- 3% of the control value (P <
      0.01). Quantitative modeling indicated that the edema in the airway wall was
      mostly outside the smooth muscle and that the smooth muscle shortening with
      histamine was similar with and without edema. We conclude that a moderate degree
      of acute airway wall thickening can lead to a potentiated constrictor response to
      histamine.

PMID- 8567569
TI  - Changes in diaphragm muscle collagen gene expression after acute unilateral
      denervation.
AB  - The purpose of the present study was to examine the effects of acute (3 days)
      unilateral diaphragm denervation (DNV) on 1) levels of alpha 1(I) and alpha
      1(III) procollagen mRNA; 2) collagen concentration [hydroxyproline (HYP)]; 3)
      amount of the nonreducible collagen cross-link hydroxylysylpyridinoline (HP); and
      4) the passive force-length relationship of the muscle. The levels of alpha 1(I)
      and alpha 1(III) procollagen mRNA, HYP concentration, and amount of HP were
      measured in muscle segments from the midcostal region of DNV and intact (INT)
      hemidiaphragms of adult male Fischer 344 rats (250-300 g). The in vitro passive
      force-length relationship of DNV and INT hemidiaphragm was determined by
      lengthening and shortening the diaphragm muscle segments from 85 to 115% of
      optimal length at a constant velocity (0.6 optimal length/s). Three days after
      DNV, the level of alpha 1(I) procollagen mRNA was increased over 15-fold in the
      DNV hemidiaphragm compared with INT (P < 0.05), whereas the level of alpha 1(III)
      procollagen mRNA was increased by approximately sixfold in the DNV hemidiaphragm
      compared with INT (P < 0.05). Collagen (HYP) concentration did not differ between
      groups, averaging 8.7 and 8.9 micrograms/mg dry wt for the DNV and INT
      hemidiaphragms, respectively. In addition, there was no difference in the amount
      of the mature nonreducible collagen cross-link HP between the DNV and INT
      hemidiaphragms (0.66 vs. 0.76 mole HP/mole collagen, respectively). The amount of
      passive force developed during lengthening did not differ between DNV and INT
      hemidiaphragms. These data indicate that acute DNV of the hemidiaphragm is
      associated with an increase in the mRNA level of the two principal fibrillar
      collagen phenotypes in skeletal muscle. However, despite extensive muscle
      remodeling, the passive force-length relationship of the DNV hemidiaphragm is
      unaffected compared with the INT muscle.

PMID- 8567570
TI  - ET-3 is extracted by and induces potent vasoconstriction in human splanchnic and
      renal vasculatures.
AB  - To investigate splanchnic and renal vascular effects and elimination of
      endothelin-3 (ET-3), ET-3 (10 pmol.kg-1.min-1 iv for 20 min) was given to six
      healthy male volunteers. Arterial plasma ET-3-like immunoreactivity (ET-3-Li)
      increased 10-fold to 111 +/- 31 pmol/l (P < 0.01). The initial half-life of
      plasma ET-3-Li determined in three subjects was 1.7 +/- 0.2 min. The fractional
      extraction of ET-3-Li was 68 +/- 7% in the splanchnic and 63 +/- 4% in the renal
      vascular beds. Mean arterial blood pressure fell from 86 +/- 4 to 94 +/- 4 mmHg
      (10%) (P < 0.05). Splanchnic and renal blood flows fell by 43 +/- 3% (P < 0.05)
      and 29 +/- 4% (P < 0.05), respectively, during the infusion. Splanchnic and renal
      vascular resistances rose by 92 +/- 22% (P < 0.05) and 58 +/- 7% (P < 0.05). In
      conclusion, ET-3 infusion in humans induces splanchnic and renal vasoconstriction
      of similar magnitude as previously shown during endothelin-1 infusion, presumably
      by ETB receptor activation. Plasma ET-3 is efficiently extracted in the
      splanchnic and renal vascular regions.

PMID- 8567571
TI  - Muscle function and protein metabolism after initiation of eccentric contraction
      induced injury.
AB  - This study was designed to determine the relationship between skeletal muscle
      function and protein metabolism after initiation of eccentric contraction-induced
      injury. Mouse anterior crural muscles were injured in vivo, and then either
      immediately or 3, 6, 24, 48, 72, 120, or 336 h after injury muscles were isolated
      and studied for indexes of muscle function, injury, phagocyte infiltration, and
      protein metabolism. A group of mice were administered anti-polymorphonuclear cell
      and anti-macrophage antisera in an attempt to reduce phagocytic infiltration into
      injured muscle. Force production in extensor digitorum longus muscles was reduced
      55% immediately after injury induction and did not recover significantly until
      120 h postinjury (28% below baseline). However, rates of protein degradation were
      not elevated until 48 h postinjury (60% above normal) and were not correlated
      with the changes in force production (r = -0.37; P = 0.24). Phagocytic
      infiltration was evident 24-120 h postinjury and was correlated with the elevated
      protein degradation rates (r = 0.75; P < 0.01). Protein synthesis rates began to
      increase approximately 48 h after injury was induced and were elevated by 83% 5
      days postinjury. Fourteen days after injury, muscle protein degradation and
      synthesis rates had returned to normal, as well as specific force production, and
      phagocytic infiltration was not detected. However, muscle mass, protein content,
      and absolute force production were lower than normal. Antisera-treated mice were
      rendered neutropenic, but there was no difference in any variable measured
      between muscles from these mice and muscles from normal mice.

PMID- 8567572
TI  - Modulation by dexamethasone of phospholipase A2 activities in endotoxemic guinea
      pigs.
AB  - One hour after lipopolysaccharide (LPS) administration (intravenous) in guinea
      pigs, alveolar macrophages are primed for an ex vivo increased secretion of
      arachidonic acid metabolites from the cyclooxygenase and the lipoxygenase
      pathways, with challenge by a second stimulus. At the same time, maximal levels
      of tumor necrosis factor-alpha (TNF-alpha) are observed in the circulation and in
      the bronchoalveolar lavage fluid. An extracellular form of phospholipase A2,
      corresponding probably to the low-molecular-mass type II enzyme, known to
      accumulate in inflammatory exudates, appears later in the serum of guinea pigs,
      to reach maximal levels 6 h after the LPS. Unlike the intracellular enzyme,
      extracellular phospholipase A2 is not increased by LPS in alveolar macrophages or
      in bronchoalveolar lavage fluids. After 24 h, at the time when neither TNF-alpha
      nor extracellular phospholipase A2 is present and priming of macrophages is over,
      maximal neutrophil infiltration is observed in the alveolar space of LPS-treated
      guinea pigs. Dexamethasone administered repeatedly during 3 days (subcutaneous)
      before the LPS challenge prevented both early events such as the macrophage
      priming and the TNF-alpha appearance and later events such as extracellular
      phospholipase A2 release and neutrophil recruitment.

PMID- 8567573
TI  - Erythropoietin levels with treatment of obstructive sleep apnea.
AB  - The effect of nasal continuous positive pressure (CPAP) treatment on
      erythropoietin (EPO) was examined by measuring diurnal serum EPO levels before
      and twice (over the 3rd day and over 1 day on recall after > or = 1 mo of
      therapy) after initiation of treatment in 12 obstructive sleep apnea syndrome
      patients with normal hemoglobin, hematocrit, creatinine, blood urea nitrogen, and
      albumin levels. Over each study day, oxygen saturation was measured by an
      ambulatory pulse oximetry system. Patients spent 27 +/- 9% (SE) of time below
      oxygen saturation of 88% vs. 2.1 +/- 0.6% after initiation of nasal CPAP
      treatment (P < 0.01). The number of desaturation events per hour of sleep before
      nasal CPAP treatment was 62 +/- 6 vs. 9 +/- 2 with nasal CPAP (P < 0.01). EPO
      levels measured by radioimmunoassay were drawn every hour before and at 3 days (n
      = 9) and before and at recall (n = 0) after initiation of CPAP therapy. The mean
      serum EPO level was higher before treatment (61 +/- 14 mU/ml) than that at 3 days
      (38 +/- 10 mU/ml, P < 0.01) or at recall (32 +/- 7 mU/ml, P < 0.01). We conclude
      that nasal CPAP treatment of sleep-disordered breathing will reduce diurnal
      levels of EPO.

PMID- 8567574
TI  - Cardiac enzyme activities in fetal and adult pregnant and nonpregnant sheep
      exposed to high-altitude hypoxemia.
AB  - We measured pyruvate kinase (PK), citrate synthase (CS), and lactate
      dehydrogenase (LDH) activities in the right and left ventricles of fetal,
      maternal, and nonpregnant adult sheep exposed to high altitude (3,820 m) for 112
      days and compared them with control groups of animals kept at sea level. Enzymes
      were assayed by the spectrophotometric appearance of reaction products specific
      to each enzyme, and activity was expressed as micromoles per minute per gram of
      wet weight of tissue. In control sheep, CS activity was significantly higher in
      both ventricles of the pregnant and nonpregnant adult compared with the fetus.
      However, LDH and PK activities were only higher in the left ventricle of the
      nonpregnant adult compared with the fetus. Long-term hypoxemia significantly
      increased LDH activities in fetal (57 and 53%), pregnant adult (29 and 27%), and
      non-pregnant adult (25 and 24%) right and left ventricles, respectively. CS
      activities also increased in fetal (90 and 97%), pregnant adult (43 and 39%), and
      nonpregnant adult (46 and 48%) right and left ventricles, respectively. However,
      PK activity was not affected by altitude in any group of animals. In the fetal
      heart, which uses lactate as its primary metabolic fuel, these enzyme changes may
      help enhance aerobic energy production during hypoxemia. In the adult heart,
      which relies on free fatty acids as well as glucose for energy production, the
      significance of these enzyme changes is less clear.

PMID- 8567575
TI  - Pulmonary gas exchange and its determinants during sustained microgravity on
      Spacelabs SLS-1 and SLS-2.
AB  - We measured resting pulmonary gas exchange in eight subjects exposed to 9 or 14
      days of microgravity (microG) during two Spacelab flights. Compared with
      preflight standing measurements, microG resulted in a significant reduction in
      tidal volume (15%) but an increase in respiratory frequency (9%). The increased
      frequency was caused chiefly by a reduction in expiratory time (10%), with a
      smaller decrease in inspiratory time (4%). Anatomic dead space (VDa) in microG
      was between preflight standing and supine values, consistent with the known
      changes in functional residual capacity. Physiological dead space (VDB) decreased
      in microG, and alveolar dead space (VDB-VDa) was significantly less in microG
      than in preflight standing (-30%) or supine (-15%), consistent with a more
      uniform topographic distribution of blood flow. The net result was that, although
      total ventilation fell, alveolar ventilation was unchanged in microG compared
      with standing in normal gravity (1 G). Expired vital capacity was increased (6%)
      compared with standing but only after the first few days of exposure to microG.
      There were no significant changes in O2 uptake, CO2 output, or end-tidal PO2 in
      microG compared with standing in 1 G. End-tidal PCO2 was unchanged on the 9-day
      flight but increased by 4.5 Torr on the 14-day flight where the PCO2 of the
      spacecraft atmosphere increased by 1-3 Torr. Cardiogenic oscillations in expired
      O2 and CO2 demonstrated the presence of residual ventilation-perfusion ratio
      (VA/Q) inequality. In addition, the change in intrabreath VA/Q during phase III
      of a long expiration was the same in microG as in preflight standing, indicating
      persisting VA/Q inequality and suggesting that during this portion of a prolonged
      exhalation the inequality in 1 G was not predominantly on a gravitationally
      induced topographic basis. However, the changes in PCO2 and VA/Q at the end of
      expiration after airway closure were consistent with a more uniform topographic
      distribution of gas exchange.

PMID- 8567576
TI  - Lung cytokinetics after exposure to hypobaria and/or hypoxia and undernutrition
      in growing rats.
AB  - Lung cellular dynamics were examined in growing rats from 4 to 7 wk of age after
      exposure to 1) room air (general controls), 2) hypobaric normoxia, 3) normobaric
      hypoxia, 4) hypobaric hypoxia, and 5) room air and restricted food intake (weight
      matched controls). Tritiated thymidine ([3H]TdR) incorporation diminished in
      weight-matched controls. In both hypoxic groups, maximum [3H]TdR incorporation
      occurred on day 3 in all cells of peripheral alveoli, capillary endothelium of
      central alveoli, airway walls and epithelium, and arterial wall and endothelium,
      but maximum [3H]TdR labeling of interstitial and unidentifiable cells of central
      alveoli occurred on day 5. The percent labeling with [3H]TdR was higher in cells
      of peripheral alveolar walls than in cells of central alveolar walls. Labeling of
      the interstitium was higher in hypobaric hypoxic than normobaric hypoxic rats. In
      hypobaric normoxia, DNA synthetic activity increased in alveolar wall cells,
      except for capillary endothelium. In hypobaric hypoxia, DNA synthesis occurred
      primarily because of low O2, but low pressure may also affect cytokinetics.
      [3H]TdR incorporation is greater and earlier in the alveoli of the peripheral
      part of the lung than central alveoli, and the cellular response of the various
      cells types is not synchronous.

PMID- 8567577
TI  - Responses of IGF-I to endogenous increases in growth hormone after heavy
      resistance exercise.
AB  - The purpose of this study was to examine the effects of a heavy-resistance
      exercise protocol known to dramatically elevate immunoreactive growth hormone
      (GH) on circulating insulin-like growth factor I (IGF-I) after the exercise
      stimulus. Seven men (23.1 +/- 2.4 yr) volunteered to participate in this study.
      Each subject was asked to perform an eight-station heavy-resistance exercise
      protocol consisting of 3 sets of 10 repetition maximum resistances with 1-min
      rest between sets and exercises followed by a recovery day. In addition, a
      control day followed a nonexercise day to provide baseline data. Pre- and
      postexercise (0, 15, and 30 min) blood samples were obtained and analyzed for
      lactate, creatinine kinase, GH, and IGF-I. Postexercise values for lactate and GH
      were significantly (P < 0.05) elevated above preexercise and resting baseline
      values. The highest mean GH concentration after the heavy-resistance exercise
      protocol was 23.8 +/- 11.8 micrograms/l, observed at the immediate postexercise
      time point. Significant increases in creatine kinase were observed after the
      exercise protocol and during the recovery day. No significant relationships were
      observed between creatine kinase and IGF-I concentrations. No significant changes
      in serum IGF-I concentrations were observed with acute exercise or between the
      recovery and control days. Thus, these data demonstrate that a high-intensity
      bout of heavy-resistance exercise that increases circulating GH did not appear to
      affect IGF-I concentrations over a 24-h recovery period in recreationally
      strength-trained and healthy young men.

PMID- 8567578
TI  - Multifrequency bioelectrical impedance estimates the distribution of body water.
AB  - Multifrequency bioelectrical impedance analysis was used to estimate the ratio of
      extracellular water (ECW) to total body water in subjects with end-stage renal
      disease. The body's resistance was measured at frequencies ranging from 1 kHz to
      1 MHz. The impedance index (height2/resistance) determined at low frequency (5
      kHz) correlated most closely with ECW (r = 0.886) using sodium bromide dilution
      as the standard of comparison. In contrast, the ratio of height squared to
      resistance determined at high frequency (500 kHz) correlated most closely with
      total body water (r = 0.974) using deuterium oxide dilution as the standard of
      comparison. The ratio of resistance at 500 kHz to resistance at 5 kHz was
      directly correlated (r = 0.767) with the ratio of ECW to total body water.
      Multifrequency bioelectrical impedance analysis may assist in the evaluation of
      body water distribution in endstage renal disease and other clinical disorders of
      fluid volume and/or distribution.

PMID- 8567579
TI  - Effects of ventilation and pleural effusion on measurements of airway thermal
      volume and blood flow in dog lungs.
AB  - We studied the effects of ventilation and pleural effusion on measurements of
      airway thermal volume (ATV) and pulmonary blood flow (PBF) by using the airway
      gas thermometry method of V. B. Serikov, M. S. Rumm, K. Kambara, M. I. Bootomo,
      A. R. Osmack, and N. C. Staub (J. Appl. Physiol. 72: 944-953, 1992) in 39
      anesthetized dogs with or without lung edema or pleural effusion. To examine the
      differential effects of increased-pressure and increased-permeability lung edema
      on accuracy and sensitivity of ATV and PBF, two models of lung edema were induced
      by intravenous infusion of a Dextran 70 solution and alloxan monohydrate,
      respectively. Dogs were hyperventilated for 3 min by using a wide range of minute
      ventilation (VE) to produce two steady-state conditions of airway temperature.
      Higher levels of VE increased an estimated amount of ATV. The ATV produced by
      hyperventilation at VE values of 559, 158, and 72 ml.min-1.kg-1 was consistent
      with the gravimetric total lung mass, the blood-free wet lung weight, and the
      extravascular lung water volume, respectively. The coefficient of lung thermal
      conductivity, a practical index of the rate of heat conduction through tissue
      from lung vessels, was related to the ratio of the decrease in expired air
      temperature to VE, and estimated PBF was consistent with the thermodilution
      cardiac output. Pleural effusion had little effect on measurements of ATV and
      PBF. However, ATV and PBF showed increased variation in dogs with dextran-induced
      lung edema.

PMID- 8567580
TI  - Neural drive to nasal dilator muscles: influence of exercise intensity and
      oronasal flow partitioning.
AB  - Our aim was to test the following hypotheses: 1) neural drive to the muscles of
      the alae nasi (AN) is proportional to nasal airflow and is independent of the
      overall level of central respiratory drive, and 2) the switch from nasal to
      oronasal breathing corresponds to the onset of marked flow turbulence in the
      nasal airway. Total and nasal inspired ventilation rates (VI) and the
      electromyogram (EMG) of the AN muscles were measured in seven subjects during
      progressive-intensity bicycling exercise. In separate experiments in six subjects
      the nasal VI corresponding to the transition from laminar to turbulent airflow
      was determined by measuring the pressure-flow relationship of the nasal airway
      with anterior rhinomanometry. Nasal VI accounted for 70 +/- 11% of total VI at
      rest and 27 +/- 8% (SE) at 90% of the maximal attainable power (max). Nasal VI
      and integrated AN EMG activities increased linearly with exercise intensity up to
      60% of the max power, but both variables plateaued at this level even though
      total VI (and central respiratory drive) began to increase exponentially as
      exercise intensity increased to 90% max. The onset of the exponential rise in
      total VI was associated with a sharp increase in oral VI and with the onset of
      marked flow turbulence in the nasal airway. The results suggest that during
      incremental exercise 1) changes in AN EMG activities are highly correlated with
      changes in nasal VI, 2) turbulent flow in the nose may be the stimulus for the
      switch to oronasal breathing so that total pulmonary resistance is minimized, and
      3) the correlation between nasal airflow and neural drive to the AN muscles is
      probably mediated by mechanisms that monitor airway resistance. Although these
      mechanisms were not identified, the most likely possibilities are receptors in
      the upper and/or lower airways that are sensitive to negative transmural
      pressure, or to effort sensations leading to greater corollary motor discharge to
      nasal dilator muscle motoneurons.

PMID- 8567581
TI  - Eccentric muscle damage transiently decreases rat skeletal muscle GLUT-4 protein.
AB  - The effects of concentric and muscle-damaging eccentric contractions on muscle
      glucose transporter GLUT-4 content were studied in rat muscles. Rats were
      anesthetized, the calf muscles on one side were stimulated electrically for
      concentric or eccentric contractions, and bilateral calf muscles were obtained in
      the postexercise period. Inflammatory and phagocytic cells accumulated in the
      eccentric white and red gastrocnemius muscles, whereas there were only discrete
      changes in the eccentric soleus. Glycogen was depleted to the same extent in the
      white and red gastrocnemius muscles after both types of stimulation, and it
      remained decreased > 2 days in eccentric muscles. The total GLUT-4 protein
      content was decreased in the eccentric white and red gastrocnemius muscles 1 and
      2 days after the eccentric stimulation, whereas the maximal activity of glycogen
      synthase was unaffected at these time points. In conclusion, our one-legged
      stimulation model caused eccentric muscle damage in the white and red
      gastrocnemius, whereas only minor damage was observed in the soleus muscle. In
      damaged muscle, muscle glycogen and GLUT-4 protein content were decreased for > 2
      days. These findings may suggest (but do not prove) that decreased muscle GLUT-4
      protein is involved in the delayed glycogen resynthesis after eccentric exercise.

PMID- 8567582
TI  - Phenyl biguanide does not inhibit locomotion in conscious rabbits.
AB  - Stimulation of cardiopulmonary vagal C fibers with phenyl biguanide (PBG)
      reflexly inhibits locomotion in addition to causing depression of blood pressure
      (BP), heart rate (HR), and respiration in cats and rats. We investigated whether
      PBG caused somatomotor inhibition during exercise in the rabbit, a species in
      which it is known that the hemodynamic and respiratory responses to PBG are
      mediated by cardiac rather than by pulmonary receptors. In eight New Zealand
      White rabbits, BP, HR, and hindlimb electromyographic (EMG) responses to 60 and
      120 micrograms/kg PBG and saline vehicle were evaluated during two separate 3-min
      exercise bouts at 10 m/min at 0% grade. During exercise, 60 micrograms/kg PBG
      decreased BP (-27 +/- 4 mmHg) and HR (-95 +/- 16 beats/min) but did not inhibit
      locomotion as suggested by the EMG response (+112 +/- 8% of preinfusion EMG).
      Hemodynamic and EMG responses to 120 micrograms/kg PBG were similar to 60
      micrograms/kg PBG. Saline infusion during exercise had no effect on HR, BP, or
      locomotion (+114 +/- 8% of preinfusion EMG). Locomotion is not inhibited by PBG
      in rabbits, which suggests that PBG-induced reflex somatomotor inhibition
      observed in other species is primarily mediated by pulmonary rather than by
      cardiac receptors.

PMID- 8567583
TI  - Role of the vascular endothelium in O2 extraction during progressive ischemia in
      canine skeletal muscle.
AB  - O2 extraction during progressive ischemia in canine skeletal muscle, J. Appl.
      Physiol. 79(4): 1351-1360, 1995.--O2 uptake (VO2) is defended during decreased O2
      delivery (QO2) by an increase in the O2 extraction ratio (O2ER, VO2/QO2),
      presumably by recruitment of capillaries. This study tested the hypothesis that
      activity of the microvascular endothelium plays a necessary role in achievement
      of maximal O2ER. We pump perfused the vascularly isolated hindlimbs of 24
      anesthetized and paralyzed dogs at progressively lower flows over a 90-min
      period. In eight dogs, hindlimb vascular endothelium was removed by injection of
      deoxycholate (DOC) into the perfusing artery before the ischemic challenge. DOC
      treatment resulted in loss of normal in vivo and in vitro endothelium-dependent
      dilatory responses to acetylcholine, but endothelium-independent vascular smooth
      muscle responses were intact. Eight other dogs were pretreated with nitro-L
      arginine methyl ester plus indomethacin (L+I group) to block the synthesis of the
      vasodilators nitric oxide and prostacyclin. L+I and DOC treatment were associated
      with increases in hindlimb vascular resistance of 168 +/- 17 and 63 +/- 12%,
      respectively. O2ER at critical QO2 (QO2 at which VO2 begins to decrease) was 81
      +/- 2% in eight control dogs, 66 +/- 6% in L+I, and 42 +/- 4% in DOC, indicating
      a significant O2 extraction defect in the two treatment groups. These data
      suggest that products of the vascular endothelium play an important role in the
      matching of O2 supply to demand during supply limitation in skeletal muscle.

PMID- 8567584
TI  - Elimination rate of 65Zn as a measure of food intake: a validation study in the
      mouse (Mus sp.).
AB  - We measured elimination of 65Zn in white mice (Mus musculus) using daily whole
      body counting. Thirteen male mice were randomly divided into three groups, each
      maintained at a different temperature. Each animal was labeled with 65Zn on day 0
      and monitored over days 0-48 postinjection. Daily food intake and body masses of
      all the animals were measured. We evaluated the ability of derived components of
      the 65Zn elimination curves to predict food intake over different phases of the
      measurement period. Food intake was significantly different between temperature
      groups; temporal variation in food intake was not intercorrelated between groups.
      Whole body elimination of 65Zn involved a rapid decline over days 0-1, followed
      by a biexponential decline in counts over days 1-48. Components of the first
      phase of the biexponential elimination curve were not significantly related to
      food intake. The rate (k2) of isotope elimination in the second phase was
      significantly related to mean food intake over days 25-48, 13-24, and 37-48. Rate
      of turnover in the second phase of elimination, incorporating the variation in
      zinc body pool size (k2 x 1/N2), where N2 is the constant of the second phase of
      elimination, was the best predictor of food intake and accounted for 60% of the
      variability over days 37-48.

PMID- 8567585
TI  - Changes in muscle proton transverse relaxation times and acidosis during exercise
      and recovery.
AB  - We studied changes in muscle proton (1H) transverse relaxation times (T2) by
      magnetic resonance imaging during exercise and compared these changes with
      alterations in muscle metabolism measured by phosphorus-31 magnetic resonance
      spectroscopy (31P-MRS). Eleven subjects completed two trials of intermittent
      incremental forearm wrist flexion exercise requiring 30 contractions/min for 5
      min, 7 min of recovery between stages, and 5-N load increments/stage. Between
      stages of the first trial, T2 images of muscle 1H were obtained. Muscle T2
      increased from 27.3 +/- 1.1 (SD) ms at rest to 35.8 +/- 3.6 ms after volitional
      fatigue (P < 0.05), whereas less active wrist extensor muscle T2 remained
      unchanged (26.8 +/- 0.9 to 28.8 +/- 1.6 ms; P > 0.05). After localizing the
      predominant muscle recruited from the T2 images, subjects completed an identical
      trial at least 1 wk later but involving surface coil 31P-MRS of the T2-enhanced
      muscle to measure the H+ concentration ([H+]). Intramuscular [H+] of T2-enhancing
      muscle increased from 1.1 +/- 0.1 x 10(-7) M at rest to 4.1 +/- 2.0 x 10(-7) M
      after volitional fatigue. Both muscle T2 and intramuscular [H+] increased in a
      bimodal manner, with T2 increasing before muscle [H+] (P < 0.05). The correlation
      coefficient between the percent change in T2 and muscle [H+] during exercise was
      +0.74 (range 0.48-0.98; P < 0.05) and +0.47 during recovery. After 12 min of
      recovery, muscle [H+] decreased to 1.4 +/- 0.3 x 10(-7) M (P < 0.05), and T2
      remained close to postexercise values (32.2 +/- 3.1 ms, P > 0.05). The data
      indicate that 1) the T2 increases during increases in exercise intensity are
      nonlinear, 2) the T2 increases during exercise are significantly correlated with
      increases in [H+], and 3) the slow recovery of T2 compared with [H+] indicates
      that [H+] has a minor contribution to the recovery in T2.

PMID- 8567586
TI  - Bubbles in circulating blood: stabilization and simulations of cyclic changes of
      size and content.
AB  - Surface tension, blood pressure, and inherent unsaturation due to O2 metabolism
      promote diffusion of gases out of bubbles in the bloodstream. We review the
      mechanisms that can overcome the absorptive tendencies so small spherical bubbles
      can persist. One general type of stabilizer is a mechanical structure at the gas
      liquid interface that can support a negative pressure so that gases inside can be
      in diffusion equilibrium with their counterparts outside; one possibility for
      mechanical stabilizers are surfactant films. We show that a slowly permeating gas
      is analogous to a mechanical stabilizer; it allows equilibration of other gases
      inside-to-outside by diluting the gases inside. By using numerically solved
      equations based on physics of diffusion, we demonstrate how nonrigid stabilized
      bubbles change size as they move through the circulatory system. In small
      pulmonary vessels, the bubbles enlarge because blood pressure is low, there is no
      inherent unsaturation, and O2 and N2 diffuse from lung gas into the bubble; these
      gases diffuse out again in the systemic circulation.

PMID- 8567587
TI  - Measurement of airway mucosal blood flow with dimethylether: validation with
      microspheres.
AB  - We have recently developed a noninvasive dimethylether (DME) uptake technique to
      estimate airway mucosal blood flow (Qaw) in humans (12). Because it was not
      feasible to validate the technique directly, we undertook the present study to
      compare Qaw as measured by DME (QDME) and by color-coded microspheres (QM) as a
      standard in seven anesthetized sheep prepared with a carotid and a left atrial
      catheter. QDME was determined by measuring DME uptake with multiple breath holds
      after passive inflation with a DME-helium gas mixture, simulating the technique
      used in humans. After the microspheres were injected into the left atrium, the
      sheep were killed and the tracheal segment corresponding to the dead space from
      which DME uptake was determined was removed, and its mucosa was stripped and
      processed for microsphere counts. Mean QDME was 35.6 ml.min-1.100 g-1 wet tissue
      (range 9.6-98.0 ml.min-1.100 g-1) and mean QM was 29.1 ml.min-1.100 g-1 (range
      7.7-91.5 ml.min-1.100 g-1). There was a strong correlation between QDME and QM (r
      = 0.89; P = 0.01). Intravenous nitroglycerin and vasopressin caused comparable
      increases and/or decreases in QDME and QM (r = 0.87; P = 0.02). This suggests
      that the noninvasive DME uptake method measures Qaw accurately and supports its
      validity in human studies.

PMID- 8567588
TI  - Endothelin-1 in heatstroke.

PMID- 8567589
TI  - Photography in the operating room, a primer: Part 1--The environment and
      equipment.

PMID- 8567590
TI  - Using medical images from the Internet in presentations.

PMID- 8567591
TI  - Kodachrome--a brief history and introduction to the film and process.

PMID- 8567592
TI  - "Regenerating neurons--MPS VII mouse brain" by James E. Hayden, RBP.

PMID- 8567593
TI  - Increasing reading and communication skills in children with autism through an
      interactive multimedia computer program.
AB  - This paper reports on the effect of using an interactive and child-initiated
      microcomputer program (Alpha) when teaching three groups of children (N = 30)
      reading and communications skills: (a) 11 children with autism (M chronological
      age, CA = 9:4 years), (b) 9 children with mixed handicaps (M CA = 13:1), and (c)
      10 normal preschool children (M CA = 6:4 years). Their mental age varied from 5:8
      years to 6:9 years and all children received computer instruction supplementary
      to their regular reading and writing activities. Tests of reading and
      phonological development were carried out at the onset of the training (Start),
      at the end (Post 1), and at a follow-up evaluation (Post 2). In addition, video
      observations of the childrens' verbal and nonverbal communication were added at
      Start and Post 1. The children with autism increased both their word reading and
      their phonological awareness through the use of the Alpha program. Clearly
      significant gains were observed during the intervention, but none during the
      follow-up period. A similar but weaker pattern is observed for the children with
      mixed handicaps. In contrast, the normal preschool children increased their
      scores regardless of the program. Analyses of the children's classroom behavior
      indicate that the intervention succeeded in stimulating verbal expressions among
      the children with autism and mixed handicap. A significant increase in enjoyment
      was also noted for the children with autism. It is concluded that the
      intervention with a motivating multimedia program might stimulate reading and
      communication in children with various developmental disabilities, but that such
      interventions must be individually based and include both detailed planning and
      monitoring from teachers, and parents, as well as from clinicians in charge.

PMID- 8567594
TI  - Efficacy of vitamin B6 and magnesium in the treatment of autism: a methodology
      review and summary of outcomes.
AB  - Pauling's orthomolecular hypothesis appeared in 1968, stating that some forms of
      mental illness and disease are related to biochemical errors in the body. Vitamin
      therapy is believed to be a means of compensating for such errors. There have
      been few empirical studies on vitamin therapy in individuals with autism. This
      article presents a critical analysis of the 12 published studies located through
      an extensive computerized search. Studies were systematically evaluated to
      provide an objective assessment of empirical evidence supporting the efficacy of
      vitamin treatment. The majority of studies report a favorable response to vitamin
      treatment. However, interpretation of these positive findings needs to be
      tempered because of methodological shortcomings inherent in many of the studies.
      For example, a number of studies employed imprecise outcome measures, were based
      on small samples and possible repeat use of the same subjects in more than one
      study, did not adjust for regression effects in measuring improvement, and
      omitted collecting long-term follow-up data. Recommendations are offered to
      assist researchers in designing future investigations.

PMID- 8567595
TI  - Life events and depression in children with pervasive developmental disorders.
AB  - To determine the role of life events in the occurrence of depression in children
      with pervasive developmental disorders (PDD), we compared 11 patients (DSM-III-R;
      9 male; 2 female; M age: 11.0 years; M full-scale IQ: 75.3) with PDD and
      depression, with an age- and sex-matched control group of patients with PDD
      without depression (DSM-III-R; 9 male; 2 female; M age: 9.8 years; M full-scale
      IQ: 60.6). Information was collected about the occurrence of unpleasant life
      events in the 12 months prior to the onset of depression. Depressed children
      experienced significantly more life events in the 12 months prior to the onset of
      depression. Exit events such as bereavement were more common in the depressed
      group. Findings suggest that, as in the general population, significant life
      events, particularly those with a negative impact, may contribute to the
      occurrence of depression in children with PDD. Future studies should explore the
      role of both biologic factors and environmental stressors in the onset of
      depression in this population.

PMID- 8567596
TI  - Impact of time delay, observational learning, and attentional cuing upon word
      recognition during integrated small-group instruction.
AB  - The effects of constant time delay, observational learning opportunities, and
      differential attentional cuing were examined during the small-group instruction
      of students in an integrated setting. Three students, one individual with
      moderate mental retardation and two individuals characterized as at-risk
      learners, participated in learning sight words through direct instruction and
      observational-learning conditions. A multiple probe design across three students
      was combined with a multitreatment design across treatment conditions to assess
      the impact of instructional variables. Reliability of scoring and procedural
      integrity were estimated and social validity of outcomes was considered. Findings
      support the salience of the constant time delay procedure in facilitating word
      acquisition in small, heterogeneous, and inclusive group learning arrangements.
      Further, a significant amount of learning through observation occurred for all
      students under both a general and specific attentional cue condition. A slight
      but discernible advantage of using the specific cuing strategy of transcribing
      target and nontarget words was realized.

PMID- 8567598
TI  - Brief report: musical interaction therapy for children with autism: an evaluative
      case study with two-year follow-up.

PMID- 8567597
TI  - Sensory modulation of auditory stimuli in children with autism and receptive
      developmental language disorder: event-related brain potential evidence.
AB  - Three groups of age- and PIQ-matched children (Autism, Receptive Developmental
      Language Disorder, and normal controls) participated in two event-related brain
      potential (ERP) experiments. Each of these experiments was aimed at evaluating
      whether either of the two clinical groups of children demonstrated abnormalities
      in two auditory ERP components, N1 and P2, which are known to be dependent on
      stimulus characteristics (frequency, intensity, and probability), and believed to
      be generated within primary and secondary cortex. Results of Experiment 1 provide
      partial support for the idea that both clinical groups failed to fully process
      changes in stimulus intensity as indexed by the N1 component. Results are
      discussed in reference to potential abnormalities in serotonergic regulation of
      auditory cortex.

PMID- 8567599
TI  - Obstetrical suboptimality in children with autism: an Italian sample.

PMID- 8567600
TI  - The combined pharmacotherapy controversy.

PMID- 8567601
TI  - Psychiatric comorbidity with problematic alcohol use in high school students.
AB  - OBJECTIVE: To delineate the degree to which various levels of problematic alcohol
      use are associated with psychiatric disorders in adolescents. METHOD: The
      lifetime occurrence of psychiatric disorders was examined in a community sample
      of 1,507 older adolescents (aged 14 through 18 years) who were categorized
      according to their alcohol use (i.e., abstainers, experimenters, social drinkers,
      problem drinkers, and abuse/dependence group). RESULTS: Increased alcohol use was
      associated with the increased lifetime occurrence of depressive disorders,
      disruptive behavior disorders, drug use disorders, and daily tobacco use. There
      was a trend for increased alcohol use in girls to be associated with anxiety
      disorders. More than 80% of adolescents with alcohol abuse/dependence had some
      other form of psychopathology. Alcohol disorders, in general, followed rather
      than preceded the onset of other psychiatric disorders. Comorbidity was
      associated with an earlier age of alcohol disorder onset and with greater
      likelihood of mental health treatment utilization. CONCLUSIONS: Rates of
      psychiatric comorbidity with problematic alcohol use in adolescents are striking
      and represent an important therapeutic challenge.

PMID- 8567602
TI  - Factors associated with the receipt of alcohol treatment services among American
      Indian adolescents.
AB  - OBJECTIVE: This study examines factors potentially associated with the receipt of
      alcohol treatment services among a large sample of American Indian adolescents.
      METHOD: Data for this study were drawn from the Voices of Indian Teens project, a
      5-year, longitudinal project involving school-based survey data collection at 10
      primarily American Indian schools. In November 1992 a total of 2,077 American
      Indian youths in grades 9 through 12 completed self-report surveys. Of these,
      1,681 had a complete set of data for these analyses. Three logistic regression
      models were developed to predict the probability of (1) receipt of treatment, (2)
      treatment recommendation, and (3) receipt of treatment among those teenagers who
      received a treatment recommendation. RESULTS: The probability of an individual
      receiving treatment was 15 times greater if treatment was recommended. Treatment
      recommendation mediated the relationship of several measures of psychological
      distress and alcohol use, abuse, and dependence with actual treatment.
      CONCLUSIONS: Recommendation for treatment is strongly associated with receiving
      treatment. Community education about the risks, signs, symptoms, need, and
      mechanisms for obtaining treatment of alcohol abuse among youths might help
      alcohol-abusing individuals receive the help they need.

PMID- 8567603
TI  - Asperger's syndrome.
AB  - This Grand Rounds is concerned with the classification of Asperger's syndrome and
      its continuity/discontinuity with autism. Information on a 15-year-old with the
      condition is presented as are data on other family members. The proband exhibited
      a longstanding pattern of marked deficits in social interaction, motor
      awkwardness, and unusual, circumscribed interest consistent with a diagnosis of
      Asperger's syndrome. Both the proband and his father exhibited unusual
      discrepancies between verbal and performance (nonverbal) cognitive abilities
      favoring the former. Deficits were observed in the social use of language. Father
      and son had similar abnormalities on magnetic resonance imaging examination.
      Potential differences between higher-functioning autism and Asperger's syndrome
      are important areas for future research.

PMID- 8567604
TI  - Trends in a national sample of sexually abusive youths.
AB  - OBJECTIVE: To describe sociodemographic factors pertinent to sexually abusive
      youths, to define common characteristics of the offending behaviors and victims,
      and to identify issues relevant to treatment recommendations. METHOD: The Uniform
      Data Collection system (UDCS), developed by the National Adolescent Perpetrator
      Network, provided data from 90 contributors in 30 states on more than 1,600
      juveniles referred to them for specialized evaluation and/or treatment following
      a sexual offense. The UDCS comprises four separate structured questionnaires that
      collect both factual information and clinical impressions. RESULTS: Physical and
      sexual abuse, neglect, and loss of a parental figure were common in these youths'
      histories. Twenty-two percent of the youths, who had been victims of sexual
      abuse, reported that the perpetrator of their own sexual abuse was female. The
      youths committed a wide range of sexual offenses, with twice as many of the
      referring offenses involving female victims than male victims. CONCLUSION: The
      discovery of sexually abusive youths across both urban and rural areas supports
      the need for comprehensive service delivery and a continuum of treatment services
      to be available in all communities.

PMID- 8567605
TI  - Etiology of Tourette's disorder.

PMID- 8567606
TI  - Risk factors for borderline pathology in children.
AB  - OBJECTIVE: To examine risk factors associated with borderline pathology in
      latency-age children. METHOD: The subjects were 98 children assessed for day
      treatment. Borderline subjects were identified in a chart review using the Child
      Diagnostic Interview for Borderlines, which divided the sample into borderline (n
      = 41) and nonborderline (n = 57) groups. Functional levels were assessed by
      Children's Global Assessment Scale scores. The risk factors were also rated by
      chart review; all subjects were given a cumulative abuse score and a cumulative
      parental dysfunction score. RESULTS: Both groups demonstrated severe functional
      impairment. The risk factors that differentiated the borderline group were sexual
      abuse, physical abuse, severe neglect, and parental substance abuse or
      criminality. Sexual abuse and severe neglect were significant in multivariate
      analysis. Cumulative abuse and cumulative parental dysfunction scores were both
      higher in the borderline group. CONCLUSIONS: The findings indicate that the risk
      factors in borderline children are similar to those found in adults.

PMID- 8567607
TI  - Guanfacine for Tourette's disorder.

PMID- 8567609
TI  - SSRI-induced mania.

PMID- 8567608
TI  - Depressed adolescents with a history of sexual abuse: diagnostic comorbidity and
      suicidality.
AB  - OBJECTIVE: To determine the nature of comorbid psychopathology and suicidality
      associated with a history of sexual abuse in depressed adolescents. METHOD:
      Twenty-four depressed adolescent inpatients with a history of sexual abuse were
      compared with a matched control group of 24 depressed adolescent inpatients on
      measures of depression, suicidal ideation and behavior, and posttraumatic stress
      disorder (PTSD) symptoms. RESULTS: Depressed adolescents with a history of sexual
      abuse had a higher prevalence of comorbid PTSD than did those without such a
      history. Chronicity and severity of abuse were significant contributors to a PTSD
      diagnosis. No differences were found in depression severity, specific depressive
      symptoms, or suicidal behavior. CONCLUSION: Comorbidity of depressive disorders
      and PTSD are common among adolescent inpatients with a history of chronic sexual
      abuse. The need for thorough assessment of depression and PTSD with appropriate
      interventions for sexually abused adolescents is clear.

PMID- 8567610
TI  - Risperidone side effects.

PMID- 8567611
TI  - A treatment outcome study for sexually abused preschool children: initial
      findings.
AB  - OBJECTIVE: Treatment outcome for sexually abused preschool-age children and their
      parents was assessed, comparing the effectiveness of a cognitive-behavioral
      intervention to nondirective supportive treatment. METHOD: Sixty-seven sexually
      abused preschool children and their parents were randomly assigned to either (1)
      cognitive-behavioral therapy adapted for sexually abused preschool children (CBT
      SAP) or (2) nondirective supportive therapy (NST). Treatment consisted of 12
      individual sessions for both the child and parent, monitored for integrity with
      the therapeutic model through intensive training and supervision, use of
      treatment manuals, and rating of audiotaped sessions. Parents completed the Child
      Behavior Checklist, the Child Sexual Behavior Inventory, and the Weekly Behavior
      Report to measure a variety of emotional and behavioral symptoms. RESULTS: Within
      group comparison of pretreatment and posttreatment outcome measures demonstrated
      that while the NST group did not change significantly with regard to
      symptomatology, the CBT-SAP group had highly significant symptomatic improvement
      on most outcome measures. Repeated-measures analyses of variance demonstrated
      group x time interactions on some variables as well. Clinical findings also
      supported the effectiveness of the CBT-SAP intervention over NST. CONCLUSIONS:
      Findings provide strong preliminary evidence for the effectiveness of a specific
      cognitive-behavioral treatment model for sexually abused preschool children and
      their parents.

PMID- 8567612
TI  - Case study: sexual abuse of boys by females.
AB  - Two examples of boys who experienced unwanted sexual contact with females are
      presented. The literature regarding this type of abuse is reviewed and supports
      the finding that such contact is relatively common and may have definite negative
      consequences for the victim. Conventional interview techniques can frequently
      fail to uncover these occurrences. Clinical, psychological, and sociocultural
      factors contribute to difficult eliciting the data. Even when young males attempt
      to report unwanted sexual contact, caregivers may fail to respond in a manner
      indicating sensitivity to the trauma. Further research could help to determine
      the long-term consequences of such experiences in male children and adolescents.

PMID- 8567613
TI  - Data-gathering tools for "real world" clinical settings: a multisite feasibility
      study.
AB  - OBJECTIVE: To determine the mental health needs and optimal treatments for
      children and families in "real world" settings, data-gathering strategies are
      needed that can be easily implemented across a variety of clinical settings. To
      address this need, the authors developed and piloted a "clinician-friendly"
      questionnaire that includes demographic, psychosocial, medical, and family
      history variables, such as those routinely gathered in standard clinical
      evaluations. METHOD: Optical scanning technology was used to encode data from
      more than 1,900 children, including 1,458 consecutive referrals in four military
      child psychiatry clinics, 285 consecutive admissions to a civilian psychiatric
      state hospital, 71 pediatric patients, and a community sample of 113 children.
      RESULTS: Despite geographic and logistic obstacles, clinical data were reliably
      obtained across multiple settings. Data analyses revealed meaningful differences
      across samples in subjects' presenting complaints, and a range of psychosocial,
      demographic, and background variables. Data were characterized by an apparently
      high degree of accuracy and completeness. CONCLUSIONS: Findings illustrate the
      importance and feasibility of standardized data-gathering approaches in routine
      clinical settings and clarify the hazards as well as the opportunities afforded
      by these research approaches. Such data-gathering tools appear to have
      significant merit and deserve further implementation and testing across a range
      of clinical and research settings.

PMID- 8567614
TI  - Current status of family-based outcome and process research.
AB  - OBJECTIVE: To review family-based treatment research. A growing body of research
      and several meta-analytic reviews demonstrate that family-based treatments are
      effective for a variety of child and adolescent disorders. In addition, an
      emerging tradition of family-based process research has begun to identify
      important ingredients of effective family psychotherapy. This article reviews
      these advances and their implications for future research. METHOD: Selected
      studies on the treatment of schizophrenia, depression, anxiety, eating disorders,
      attention deficit, conduct disorder, and substance abuse are reviewed, as well as
      several process research and meta-analytic studies. RESULTS: Family-based
      therapies have been shown to be effective for treating schizophrenia, conduct
      disorder, and substance abuse. Some data support their effectiveness in the
      treatment of eating disorders. Few studies have targeted internalizing disorders.
      A process research tradition is emerging, but it is in need of methodological
      advances. Meta-analytic studies suggest that family-based therapies are as
      effective as other models. CONCLUSIONS: More well-designed studies with diverse
      populations are needed to assess accurately the effectiveness of this
      increasingly popular treatment approach.

PMID- 8567615
TI  - Diagnostic utility of endocrine and neuroimaging screening tests in first-onset
      adolescent psychosis.
AB  - OBJECTIVE: To determine the diagnostic utility of endocrine and neuroimaging
      screening tests in first-onset adolescent psychosis. METHOD: 111 consecutively
      admitted adolescents (aged 13 through 19 years) who presented with a first-onset
      psychosis and who had an unremarkable medical history and normal physical
      examination were given a battery of endocrine and neuroimaging screening tests.
      Diagnostic utility of a screening test was defined as an abnormal result (a
      positive test) that either led to a previously unknown or unsuspected medical
      diagnosis or played an important role in the clinical care of the patient.
      RESULTS: 15.4% of the endocrine screening tests and 11.0% of the neuroimaging
      screening tests were identified as positive. However, no endocrine and no
      neuroimaging tests met criteria for diagnostic utility. The direct cost of this
      screening battery was $636.95 per patient. CONCLUSION: Routine endocrine and
      neuroimaging screening tests in first-onset adolescent psychosis provide no
      diagnostic utility and are not cost-effective. Selective use of appropriate
      endocrine and neuroimaging diagnostic tests in populations with symptoms
      suggestive of organic disorders should replace routine screening procedures.

PMID- 8567616
TI  - Who gets hospitalized in a continuum of care?
AB  - OBJECTIVE: To compare children and adolescents hospitalized under a continuum of
      care with those hospitalized under traditional insurance coverage. METHOD: With
      comprehensive data, logistic regressions were used to predict hospitalization and
      to identify its determinants. RESULTS: As expected, the probability of being
      hospitalized was much higher under traditional care. In addition, the predictors
      of hospitalization differed by site. Accuracy of predictions was high.
      CONCLUSIONS: Different kinds of children were hospitalized under a continuum of
      care than under a traditional insurance system. Hospitalizations under both
      systems were highly predictable.

PMID- 8567617
TI  - Results of treatment one year later: child and adolescent partial
      hospitalization.
AB  - OBJECTIVE: One criticism of academicians is that they evaluate and disseminate
      outcome studies based more on the value and merit of the research design than on
      the utility of the findings for improving clinical practice. Increasing pressure
      on programs to evaluate the effectiveness of behavioral health care is
      transitioning outcome measurement from the exclusive domain of the researcher
      toward the clinical/organizational domain. To explore the multiple applications
      of such clinical outcome data, this article presents the results from a study of
      114 patients completing treatment in two child and adolescent partial hospital
      programs. METHOD: Four areas define the scope of clinical outcome measurement
      pertinent to partial hospitalization: changes in the patient's clinical status,
      changes in the patient's level of daily functioning, impact on the utilization of
      behavioral health services after discharge, and patient/family satisfaction with
      treatment. Using these four domains, this study compares data assessed at
      admission and at 1 year postdischarge. RESULTS: Analyses used paired t tests
      primarily to measure change between admission and 1 year after discharge.
      Overall, the data show improvement in general functioning that remains evident up
      to 1 year postdischarge. CONCLUSIONS: Finding positive results in specific areas
      emphasized therapeutically--such as family functioning and use of community-based
      mental health resources after discharge, and the parent's attribution of
      improvement to experiences in treatment--provides justification for relating
      improvement to the treatment episode.

PMID- 8567618
TI  - Impact of parent monitoring on initiation of drug use through late childhood.
AB  - OBJECTIVE: To examine whether parental supervision and monitoring in middle
      childhood might have a sustained impact on risk of drug use later in childhood
      and adolescence. METHOD: An epidemiological sample of 926 urban-dwelling youths
      were individually interviewed annually, beginning in 1989 when the children were
      8 to 10 years old, continuing through 1992. Standardized questions measured drug
      use, parenting behaviors, and other suspected determinants of drug use. RESULTS:
      Survival analysis estimates indicated that children in the lowest quartile of
      parent monitoring initiated drug use at earlier ages. The contrast in risk of
      initiating alcohol, tobacco, or other drug use across levels of parent monitoring
      was greatest when children were under 11 years old; at older ages there was no
      difference in risk. However, in analyses focused specifically on marijuana,
      cocaine, and inhalant drugs, we observed a sustained higher risk of starting to
      use these drugs among youths who had been monitored at the lowest levels in
      middle childhood. CONCLUSION: These results add to the chain of inference that
      effective supervision and monitoring in middle childhood by parents or guardians
      might induce a delay or prevent onset of drug use among youths living in urban
      areas, a hypothesis that now ought to be tested in rigorous field experiments.

PMID- 8567619
TI  - Identification of residues within the SHC phosphotyrosine binding/phosphotyrosine
      interaction domain crucial for phosphopeptide interaction.
AB  - Shc is an Src homology 2 (SH2) domain protein thought to be an important
      component of the signaling pathway leading from cell surface receptors to Ras. A
      new phosphotyrosine interaction (PI) domain (also known as the phosphotyrosine
      binding (PTB) domain) has been described in the amino terminus of Shc. The Shc PI
      domain binding specificity is dependent on residues lying amino-terminal to the
      phosphotyrosine rather than carboxyl-terminal as is seen with SH2 domains. We
      randomly mutagenized the Shc PTB/PI domain in an effort to identify residues in
      the domain crucial for interaction with phosphotyrosine-containing peptides. We
      then screened the mutants for binding to the tyrosine-phosphorylated carboxyl
      terminal tail of the epidermal growth factor (EGF) receptor. Most striking were
      mutations that altered a phenylalanine residue in block 4 of the domain severely
      impairing PI domain function. This phenylalanine residue is conserved in all but
      one subfamily of PI domains that have been identified to date. Reconstitution of
      this phenylalanine mutation into full-length Shc created a protein unable to
      interact with the EGF receptor in living cells.

PMID- 8567620
TI  - Single chain human interleukin 5 and its asymmetric mutagenesis for mapping
      receptor binding sites.
AB  - Wild type human (h) interleukin 5 (wt IL5) is composed of two identical peptide
      chains linked by disulfide bonds. A gene encoding a single chain form of hIL5
      dimer was constructed by linking the two hIL5 chain coding regions with Gly-Gly
      linker. Expression of this gene in COS cells yielded a single chain IL5 protein
      (sc IL5) having biological activity similar to that of wt IL5, as judged by
      stimulation of human cell proliferation. Single chain and wt IL5 also had similar
      binding affinity for soluble IL5 receptor alpha chain, the specificity subunit of
      the IL5 receptor, as measured kinetically with an optical biosensor. The design
      of functionally active sc IL5 molecule. Such mutagenesis was exemplified by
      changes at residues Glu-13, Arg-91, Glu-110, and Trp-111. The receptor binding
      and bioactivity data obtained are consistent with a model in which residues from
      both IL5 monomers interact with the receptor alpha chain, while the interaction
      likely is asymmetric due to the intrinsic asymmetry of folded receptor. The
      results demonstrate a general route to the further mapping of receptor and other
      binding sites on the surface of human IL5.

PMID- 8567621
TI  - The quantal nature of calcium release to caffeine in single smooth muscle cells
      results from activation of the sarcoplasmic reticulum Ca(2+)-ATPase.
AB  - Calcium release from intracellular stores occurs in a graded manner in response
      to increasing concentrations of either inositol 1,4,5-trisphosphate or caffeine.
      To investigate the mechanism responsible for this quantal release phenomenon,
      [Ca2+] changes inside intracellular stores in isolated single smooth muscle cells
      were monitored with mag-fura 2. Following permeabilization with saponin or alpha
      toxin the dye, loaded via its acetoxymethyl ester, was predominantly trapped in
      the sarcoplasmic reticulum (SR). Low caffeine concentrations in the absence of
      ATP induced only partial Ca2+ release; however, after inhibiting the calcium pump
      with thapsigargin the same stimulus released twice as much Ca2+. When the SR
      Ca(2+)-ATPase was rendered non-functional by depleting its "ATP pool," submaximal
      caffeine doses almost fully emptied the stores of Ca2+. We conclude that quantal
      release of Ca2+ in response to caffeine in these smooth muscle cells is largely
      due to the activity of the SR Ca(2+)-ATPase, which appears to return a portion of
      the released Ca2+ back to the SR, even in the absence of ATP. Apparently the SR
      Ca(2+)-ATPase is fueled by ATP, which is either compartmentalized or bound to the
      SR.

PMID- 8567622
TI  - Identification and characterization of CPP32/Mch2 homolog 1, a novel cysteine
      protease similar to CPP32.
AB  - We have identified and characterized a novel cysteine protease named CMH-1 that
      is a new member of the interleukin 1 beta converting enzyme (ICE) family of
      proteases with substrate specificity for Asp-X. CMH-1 has the highest similarity
      to CPP32 (52% amino acid identity) and MCH2 (31% identical). CMH-1 shares
      conserved amino acid residues that form the core structure of ICE as well as
      those residues involved in catalysis and in the P1 aspartate binding.
      Overexpression of CMH-1 in COS cells resulted in the processing of CMH-1 and the
      induction of apoptosis of transfected cells. Coexpression of CMH-1 with poly(ADP
      ribose) polymerase (PARP) also resulted in a specific cleavage of PARP. Purified
      recombinant CMH-1 cleaved PARP but not interleukin 1 beta precursor in vitro.

PMID- 8567623
TI  - A human polysialyltransferase directs in vitro synthesis of polysialic acid.
AB  - Polysialic acid (PSA) is a linear homopolymer of alpha-2,8-linked sialic acid
      residues whose expression is developmentally regulated and modulates the adhesive
      property of the neural adhesion molecule, N-CAM. Recently, hamster and human
      cDNAs encoding polysialyltransferase (PST-1 for the hamster enzyme and PST for
      the human enzyme) were cloned, and by using the human cDNA it was demonstrated
      that the expression of PSA in N-CAM facilitates neurite outgrowth (Nakayama, J.,
      Fukuda, M.N., Fredette, B., Ranscht, B., and Fukuda, M. (1995) Proc. Natl. Acad.
      Sci. U.S.A., 92, 7031-7035; Eckhardt, M.A., Muhlenhoff, M., Bethe, A., Koopman,
      J., Frosch, M., and Gerardy-Schahn, R. (1995) Nature 373, 715-718.) Although
      these studies demonstrated that PST-1 and PST synthesize PSA in cultured cells,
      it was not shown that they could catalyze the polycondensation of alpha-2,8
      linked sialic acid on a glycoconjugate template containing alpha-2,3-linked
      sialic acid. Here we demonstrate that PSA formation by PST is independent from
      the presence of N-CAM in vivo. We then develop an in vitro assay of PSA synthesis
      using glycoproteins other than N-CAM as acceptors and a soluble PST as an enzyme
      source. The soluble PST, produced as a chimeric protein fused with protein A, was
      incubated with rat alpha 1-acid glycoprotein, fetuin or human alpha 1-acid
      glycoprotein as acceptors together with the donor substrate CMP-[14C]NeuNAc.
      Incubation of fetuin with the soluble PST, in particular, resulted in a high
      molecular weight product that was susceptible to PSA-specific endoneuraminidase.
      Polysialylated products were not formed when alpha-2,3-linked sialic acid was
      removed from the acceptor fetuin before incubation. These results establish that
      a single enzyme, PST, alone can catalyze both the addition of the first alpha-2,8
      linked sialic acid to alpha-2,3-linked sialic acid and the polycondensation of
      all alpha-2,8-linked sialic acids, yielding PSA.

PMID- 8567624
TI  - Regulation of fatty acid elongation and initiation by acyl-acyl carrier protein
      in Escherichia coli.
AB  - Long chain acyl-acyl carrier protein (acyl-ACP) has been implicated as a
      physiological inhibitor of fatty acid biosynthesis since acyl-ACP degradation by
      thioesterase overexpression leads to constitutive, unregulated fatty acid
      production. The biochemical targets for acyl-ACP inhibition were unknown, and
      this work identified two biosynthetic enzymes that were sensitive to acyl-ACP
      feedback inhibition. Palmitoyl-ACP inhibited the incorporation of [14C]malonyl
      CoA into long chain fatty acids in cell-free extracts of Escherichia coli. A
      short chain acyl-ACP species with the electrophoretic properties of beta
      hydroxybutyryl-ACP accumulated concomitant with the overall decrease in the
      amount of [14C]malonyl-CoA incorporation, indicating that the first elongation
      cycle was targeted by acyl-ACP. All of the proteins required to catalyze the
      first round of fatty acid synthesis from acetyl-CoA plus malonyl-CoA in vitro
      were isolated, and the first fatty acid elongation cycle was reconstituted with
      these purified components. Analysis of the individual enzymes and the pattern of
      intermediate accumulation in the reconstituted system identified initiation of
      fatty acid synthesis by beta-ketoacyl-ACP synthase III (fabH) and enoyl-ACP
      reductase (fabI) in the elongation cycle as two steps attenuated by long chain
      acyl-ACP.

PMID- 8567625
TI  - Accurate scanning of the BssHII endonuclease in search for its DNA cleavage site.
AB  - A facilitated diffusion mechanism has been proposed to account for the kinetic
      efficiency with which restriction endonucleases are able to locate DNA
      recognition sites. Such a mechanism involves the initial formation of a
      nonspecific complex upon collision of the protein with the DNA, with the
      subsequent diffusion of the protein along the DNA helix until either a
      recognition site is located or the protein dissociates into solution. Protein
      translocation may be facilitated by either sliding along the DNA, hopping to
      nearby sites, or intersegment transfer over larger distances. Previous analyses
      of the manner in which restriction enzymes cleave DNA substrates did rule out the
      latter mechanism. To discriminate between protein sliding or scanning and protein
      hopping, we designed a unique DNA template with three overlapping, mutually
      exclusive recognition sites for the BssHII endonuclease. Analysis of the cleavage
      pattern demonstrated efficient usage of both external sites, whereas the
      centrally located site was not efficiently cleaved. These results confirm that
      linear diffusion of the BssHII enzyme occurs by scanning along the DNA.
      Furthermore, the scanning enzyme was found to stop and cleave at the first site
      encountered. Thus, a sliding restriction endonuclease recognizes cleavage sites
      with high fidelity, without skipping of potential sites.

PMID- 8567626
TI  - CPP32/apopain is a key interleukin 1 beta converting enzyme-like protease
      involved in Fas-mediated apoptosis.
AB  - Cysteine proteases of the interleukin 1 beta Converting Enzyme (ICE)/CED-3 family
      have been implicated in the effector process of apoptosis in several systems,
      including Fas-mediated apoptosis. We have recently isolated and partially
      characterized a protease present in extracts from anti-Fas antibody treated
      Jurkat T cells that promotes apoptotic changes in isolated nuclei (Schlegel, J.,
      Peters, I., and Orrenius, S. (1995) FEBS Lett. 364, 139-142). We now show that
      this protease cleaves poly-(ADP-ribose) polymerase (PARP) with high efficiency
      and specificity. Both PARP proteolysis and the proapoptotic effects of the
      protease are inhibited by nanomolar concentrations of a selective inhibitor of
      apopain (CPP32), while an inhibitor of IL-1 beta converting enzyme is much less
      effective, requiring micromolar concentrations for the inhibition of the isolated
      protease. Kinetic analysis of the isolated protease reveals kinetic constants
      similar to those reported for apopain. The isolated protease is recognized by
      antibodies specific for CPP32/apopain but not by an anti-ICE antibody.
      Furthermore, a selective inhibitor of apopain prevents Fas-induced apoptosis in
      intact Jurkat T cells. We therefore conclude that CPP32/apopain is activated in
      Fas-induced apoptosis.

PMID- 8567627
TI  - Precision targeting of protein kinases. An affinity label that inactivates the
      cGMP- but not the cAMP-dependent protein kinase.
AB  - Although the cAMP-dependent (PKA) and cGMP-dependent protein kinases (PKG)
      usually participate in unrelated biological processes, their enzymological
      properties are decidedly similar. Based upon the multitude of comparative studies
      conducted to date, it appears that these two enzymes exhibit very similar peptide
      substrate specificities. Furthermore, most inhibitors that have been reported for
      PKG serve in a nearly equal capacity for PKA. Consequently, the task of
      distinguishing between these enzymes, especially under in vivo conditions, has
      proved to be daunting. However, we have recently found that PKA will only
      phosphorylate non-amino acid residues whose alpha-configuration corresponds to
      that found in L-amino acids, whereas PKG will catalyze the phosphorylation of
      residues corresponding to both L- and D-amino acids (Wood, J., Mendelow, M., Yan,
      X., Corbin, J.D., Francis, S.H., and Lawrence, D.S. (1996) J. Biol. Chem. 271,
      174-179). Based on these results, we have designed a potent affinity label for
      PKG (KI = 21.1 +/- 4.7 microM), that has no measurable activity toward PKA. This
      represents the first example of an peptide-based inactivator that fully
      distinguishes between these two closely related enzymes. These results suggest
      that a similar strategy may provide highly specific inactivators for other
      protein kinases as well.

PMID- 8567628
TI  - Functional organization of mammalian hexokinase II. Retention of catalytic and
      regulatory functions in both the NH2- and COOH-terminal halves.
AB  - The mammalian hexokinase (HK) family includes three closely related 100-kDa
      isoforms (HKI-III) that are thought to have arisen from a common 50-kDa precursor
      by gene duplication and tandem ligation. Previous studies of HKI indicated that a
      glucose 6-phosphate (Glu-6-P)-regulated catalytic site resides in the COOH
      terminal half of the molecule and that the NH2-terminal half contains only a Glu
      6-P binding site. In contrast, we now show that proteins representing both halves
      of human and rat HKII have catalytic activity and that each is inhibited by Glu-6
      P. The intact enzyme and the NH2- and COOH-terminal halves of the enzyme each
      increase glucose utilization when expressed in Xenopus oocytes. Mutations
      corresponding to either Asp-209 or Asp-657 in the intact enzyme completely
      inactivate the NH2- and COOH-terminal half enzymes, respectively. Mutation of
      either of these sites results in a 50% reduction of activity in the 100-kDa
      enzyme. Mutation of both sites results in a complete loss of activity. This
      suggests that each half of the HKII molecule retains catalytic activity within
      the 100-kDa protein. These observations indicate that HKI and HKII are
      functionally distinct and have evolved differently.

PMID- 8567629
TI  - CTG triplet repeats from human hereditary diseases are dominant genetic expansion
      products in Escherichia coli.
AB  - The relative ability of the 10 triplet repeat sequences to be expanded in
      Escherichia coli was determined. Surprisingly, CTG tracts are expanded at least 8
      times more frequently than any of the other nine triplets. Low levels of
      expansion were found also for CGG, GTG, and GTC. Thus, the structure of the CTG
      repeats and/or their utilization by the DNA synthetic systems in vivo must be
      quite different from the other triplets. These data further validate this
      genetically defined system for elucidating molecular mechanisms of expansion and
      may explain why most triplet repeat hereditary neuromuscular and
      neurodegenerative disease genes contain CTG repeats.

PMID- 8567630
TI  - Two isoforms of the prostaglandin E receptor EP3 subtype different in agonist
      independent constitutive activity.
AB  - We previously identified two isoforms of the mouse prostaglandin E receptor EP3
      subtype, EP3 alpha and EP3 beta, with different carboxyl-terminal tails, produced
      through alternative splicing and showing different efficiency in inhibition of
      adenylate cyclase (Sugimoto, Y., Negishi, M., Hayashi, Y., Namba, T., Honda, A.,
      Watabe, A., Hirata, M., Narumiya, S., and Ichikawa, A. (1993) J. Biol. Chem. 268,
      2712-2718). To assess the role of the carboxyl-terminal tails in the G protein
      coupling properties of the EP3 receptor, we examined the Gi activities of EP3
      alpha, EP3 beta, and the mutant receptor, in which the carboxyl-terminal tail was
      truncated at the splicing site. The EP3 alpha receptor showed marked agonist
      independent constitutive inhibition of adenylate cyclase, while EP3 beta receptor
      had no agonist-independent inhibition. On the other hand, the truncated receptor
      showed only agonist-independent constitutive inhibition. The constitutive
      activity of these receptors on the stimulation of GTPase activity of Gi was also
      observed. Thus, alternative splicing produced two isoforms with different
      carboxyl-terminal tails and with different constitutive activity, and the
      truncation of the carboxyl-terminal tail caused full constitutive activity.

PMID- 8567631
TI  - p-Hydroxyphenylacetaldehyde is the major product of L-tyrosine oxidation by
      activated human phagocytes. A chloride-dependent mechanism for the conversion of
      free amino acids into reactive aldehydes by myeloperoxidase.
AB  - Reactive aldehydes generated during lipid peroxidation have been implicated in
      the pathogenesis of atherosclerosis as well as other inflammatory diseases. A
      potential catalyst for such reactions is myeloperoxidase, a hemeprotein secreted
      by activated phagocytes. We now report that activated neutrophils utilize the
      myeloperoxidase-H2O2-chloride system to convert L-tyrosine to p
      hydroxyphenylacetaldehyde. Production of p-hydroxyphenylacetaldehyde was nearly
      quantitative at physiological concentrations of L-tyrosine and chloride. Aldehyde
      generation required myeloperoxidase, H2O2, L-tyrosine, and chloride ion; it was
      inhibited by the H2O2 scavenger catalase and by the heme poisons azide and
      cyanide. Phorbol ester- and calcium ionophore-stimulated human neutrophils
      likewise generated p-hydroxyphenylacetaldehyde from L-tyrosine by a pathway
      inhibited by azide, cyanide, and catalase. Aldehyde production accounted for 75%
      of H2O2 generated by optimally stimulated neutrophils at plasma concentrations of
      L-tyrosine and chloride. Collectively, these results indicate that activated
      phagocytes, under physiological conditions, utilize myeloperoxidase to execute
      the chloride-dependent conversion of L-tyrosine to the lipid-soluble aldehyde, p
      hydroxyphenylacetaldehyde, in near quantitative yield. Moreover, like aldehydes
      derived from lipid peroxidation, amino acid-derived aldehydes may exert potent
      biological effects in vascular lesions and other sites of inflammation.

PMID- 8567632
TI  - Purification and characterization of diacylglycerol pyrophosphate phosphatase
      from Saccharomyces cerevisiae.
AB  - Diacylglycerol pyrophosphate (DGPP) phosphatase is a novel membrane-associated
      enzyme that catalyzes the dephosphorylation of the beta phosphate of DGPP to
      yield phosphatidate and Pi. DGPP phosphatase was purified 33,333-fold from
      Saccharomyces cerevisiae by a procedure that included Triton X-100 solubilization
      of microsomal membranes followed by chromatography with DE53, Affi-Gel Blue,
      hydroxylapatite, and Mono Q. The procedure resulted in the isolation of an
      apparent homogeneous protein with a subunit molecular mass of 34 kDa. DGPP
      phosphatase activity was associated with the 34-kDa protein. DGPP phosphatase had
      a broad pH optimum between 6.0 and 8.5 and was dependent on Triton X-100 for
      maximum activity. The enzyme was inhibited by divalent cations, NaF, and
      pyrophosphate and was relatively insensitive to thioreactive agents. The turnover
      number (molecular activity) for the enzyme was 5.8 x 10(3) min-1 at pH 6.5 and 30
      degrees C. DGPP phosphatase exhibited typical saturation kinetics with respect to
      DGPP (Km = 0.55 mol %). The Km value for DGPP was 3-fold greater than its
      cellular concentration (0.18 mol %). DGPP phosphatase also catalyzed the
      dephosphorylation of phosphatidate, but this dephosphorylation was subsequent to
      the dephosphorylation of the beta phosphate of DGPP. The dependence of activity
      on phosphatidate (Km = 2.2 mol %) was cooperative (Hill number = 2.0). DGPP was
      the preferred substrate for the enzyme with a specificity constant (Vmax/Km) 10
      fold greater than that for phosphatidate. In addition, DGPP potently inhibited
      (Ki = 0.35 mol %) the dephosphorylation of phosphatidate by a competitive
      mechanism whereas phosphatidate did not inhibit the dephosphorylation of DGPP.
      DGPP was neither a substrate nor an inhibitor of pure phosphatidate phosphatase
      from S. cerevisiae. DGPP was synthesized from phosphatidate via the phosphatidate
      kinase reaction.

PMID- 8567633
TI  - Altered drug-stimulated ATPase activity in mutants of the human multidrug
      resistance protein.
AB  - The characteristics of P-glycoprotein (MDR1), an ATP-dependent drug extrusion
      pump responsible for the multidrug resistance of human cancer, were investigated
      in an in vitro expression system. The wild-type and several mutants of the human
      MDR1 cDNA were engineered into recombinant baculoviruses and the mutant proteins
      were expressed in Sf9 insect cells. In isolated cell membrane preparations of the
      virus-infected cells the MDR1-dependent drug-stimulated ATPase activity, and 8
      azido-ATP binding to the MDR1 protein were studied. We found that when lysines
      433 and/or 1076 were replaced by methionines in the ATP-binding domains, all
      these mutations abolished drug-stimulated ATPase activity independent of the
      MgATP concentrations applied. Photoaffinity labeling with 8-azido-ATP showed that
      the double lysine mutant had a decreased ATP-binding affinity. In the MDR1 mutant
      containing a Gly185 to Val replacement we found no significant alteration in the
      maximum activity of the MDR1-ATPase or in its activation by verapamil and
      vinblastine, and this mutation did not modify the MgATP affinity or the 8-azido
      ATP binding of the transporter either. However, the Gly185 to Val mutation
      significantly increased the stimulation of the MDR1-ATPase by colchicine and
      etoposide, while slightly decreasing its stimulation by vincristine. These shifts
      closely correspond to the effects of this mutation on the drug-resistance
      profile, as observed in tumor cells. These data indicate that the Sf9-baculovirus
      expression system for MDR1 provides an efficient tool for examining structure
      function relationships and molecular characteristics of this clinically important
      enzyme.

PMID- 8567634
TI  - Nif- phenotype of Azotobacter vinelandii UW97. Characterization and mutational
      analysis.
AB  - We have identified the molecular basis for the nitrogenase negative phenotype
      exhibited by Azotobacter vinelandii UW97. This strain was initially isolated
      following nitrosoguanidine mutagenesis. Recently, it was shown that this strain
      lacks the Fe protein activity, which results in the synthesis of a FeMo cofactor
      deficient apodinitrogenase. Activation of this apodinitrogenase requires the
      addition of both MgATP and wild-type Fe protein to the crude extracts made by A.
      vinelandii UW97 (Allen, R.M., Homer, M.J., Chatterjee R., Ludden, P.W., Roberts,
      G.P., and Shah, V.K. (1993) J. Biol. Chem. 268 23670-23674). Earlier, we proposed
      the sequence of events in the MoFe protein assembly based on the biochemical and
      spectroscopic analysis of the purified apodinitrogenase from A. vinelandii DJ54
      (Gavini, N., Ma, L., Watt, G., and Burgess, B.K. (1994) Biochemistry 33, 11842
      11849). Taken together, these results imply that the assembly process of
      apodinitrogenase is arrested at the same step in both of these strains. Since A.
      vinelandii DJ54 is a delta nifH strain, this strain is not useful in identifying
      the features of the Fe protein involved in the MoFe protein assembly. Here, we
      report a systematic analysis of an A. vinelandii UW97 mutant and show that,
      unlike A. vinelandii DJ54, the nifH gene of A. vinelandii UW97 has no deletion in
      either coding sequence or the surrounding sequences. The specific mutation
      responsible for the Nif- phenotype of A. vinelandii UW97 is the substitution of a
      non-conserved serine at position 44 of the Fe protein by a phenylalanine as shown
      by DNA sequencing. Furthermore, oligonucleotide site-directed mutagenesis was
      employed to confirm that the Nif- phenotype in A. vinelandii UW97 is exclusively
      due to the substitution of the Fe protein residue serine 44 by phenylalanine. By
      contrast, replacing Ser-44 with alanine did not affect the Nif phenotype of A.
      vinelandii. Therefore, it seems that the Nif- phenotype of A. vinelandii UW97 is
      caused by a general structural disturbance of the Fe protein due to the presence
      of the bulky phenylalanine at position 44.

PMID- 8567636
TI  - RNA editing is required for efficient excision of tRNA(Phe) from precursors in
      plant mitochondria.
AB  - RNA editing corrects a 4C-A69 mismatch to a conventional 4T-A69 Watson-Crick base
      pair in the acceptor stem of the mitochondrially encoded tRNAPhe in plants. In
      vitro processing of edited and unedited Oenothera tRNA Phe precursor RNAs with
      pea mitochondrial protein extracts shows a significant effect of this RNA-editing
      event on the efficiency of 5' and 3' processing. While mature tRNA molecules are
      rapidly generated by in vitro processing from edited precursors, the formation of
      mature tRNAs from unedited pre-tRNAs is considerably reduced. Primer extension
      analyses of in vitro processing products show that processing at both 5' and 3'
      termini is governed by the RNA-editing event. Investigation of edited and
      unedited precursor RNAs by lead cleavage experiments reveals differences in the
      higher order structures of the pre-tRNAs. The differing conformations are most
      likely responsible for the altered processing efficiencies of edited and unedited
      precursor molecules. RNA editing of the tRNAPhe precursors is thus a prerequisite
      for efficient excision of the mature tRNAPhe in vitro. Hence RNA editing might be
      involved in regulating the amount of mature tRNAPhe in the steady state RNA pool
      of mitochondria in higher plants.

PMID- 8567635
TI  - Insulin regulation of phosphoenolpyruvate carboxykinase gene expression does not
      require activation of the Ras/mitogen-activated protein kinase signaling pathway.
AB  - Expression of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting step
      in hepatic gluconeogenesis, is primarily regulated at the level of gene
      transcription. Insulin and phorbol esters inhibit basal PEPCK transcription and
      antagonize the induction of PEPCK gene expression by glucocorticoids and glucagon
      (or its second messenger cAMP). Insulin activates a signaling cascade involving
      Ras --> Raf --> p42/p44 mitogen-activated protein (MAP) kinase kinase (MEK) -->
      p42/p44 MAP kinase (ERK 1 and 2). Recent reports suggest that activation of this
      Ras/MAP kinase pathway is critical for the effects of insulin on mitogenesis and
      c-fos transcription but is not required for insulin action on metabolic processes
      such as glycogen synthesis, lipogenesis, and Glut-4-mediated glucose transport.
      We have used three distinct approaches to examine the role of the Ras/MAP kinase
      pathway in the regulation of PEPCK transcription by insulin in H4IIE-derived
      liver cells: (i) chemical inhibition of Ras farnesylation, (ii) infection of
      cells with an adenovirus vector encoding a dominant-negative mutant of Ras, and
      (iii) use of a chemical inhibitor of MEK. Although each of these methods blocks
      insulin activation of MAP kinase, none alters insulin antagonism of cAMP- and
      glucocorticoid-stimulated PEPCK transcription. Although phorbol esters activate
      MAP kinase and mimic the effects of insulin on PEPCK gene transcription,
      inhibition of MEK has no effect on phorbol ester inhibition of PEPCK gene
      transcription. Using the structurally and mechanistically distinct
      phosphatidylinositol 3-kinase (PI 3-kinase) inhibitors, wortmannin and LY 294002,
      we provide further evidence supporting a role for PI 3-kinase activation in the
      regulation of PEPCK gene transcription by insulin. We conclude that neither
      insulin nor phorbol ester regulation of PEPCK gene transcription requires
      activation of the Ras/MAP kinase pathway and that insulin signaling to the PEPCK
      promoter is dependent on PI 3-kinase activation.

PMID- 8567637
TI  - Dimerization of the gastric H+, K(+)-ATPase.
AB  - When the gastric H+, K(+)-ATPase was solubilized by n-dodecyl beta-D-maltoside
      and electrophoresed in blue native-polyacrylamide gels (BN-PAGE), one major band
      at about 360 kDa was observed. Since this band was recognized by both monoclonal
      antibodies 1218 (anti-alpha) and wheat germ agglutinin (anti-beta), the H+, K(+)
      ATPase in its native state exists in a dimeric (alpha beta)2 form. The site of
      interaction between the heterodimers was determined using Cu(2+)-phenanthroline
      cross-linking. The Cu(2+)-phenanthroline reagent reacted with the H+, K(2+)
      ATPase activity. This cross-linking and enzyme inhibition were prevented by ATP.
      Cross-linking followed by N-ethylmaleimide blockade of maleimide-reactive SH
      groups, then reduction and fluorescein 5-maleimide labeling, then reduction and
      fluorescent tryptic peptide of about 6.5 kDa that had been cross-linked. Since
      its N-terminal amino acid is Val561, the peptide probably ends at Arg616 or
      Arg621 and Cys565 and/or Cys615 are probably within the region of closest contact
      between the two alpha-subunits.

PMID- 8567638
TI  - Function of the human insulin promoter in primary cultured islet cells.
AB  - Pancreatic islet beta cells regulate the rate of insulin gene transcription in
      response to a number of nutrients, the most potent of which is glucose. To test
      for its regulation by glucose, the promoter sequence was isolated from the human
      insulin gene. When linked to chloramphenicol acetyltransferase and transfected
      into primary islet cultures, the human insulin promoter is activated by glucose.
      In parallel islet transfections, glucose also activates the L-pyruvate kinase and
      islet amyloid chain ketoacid dehydrogenase E1a promoter, but it does not affect
      the beta cell glucose kinase promoter. Using deletion and substitution mutations
      of the proximal human insulin promoter, we mapped a metabolic response element to
      the E box, E1, at -100 base pairs relative to the transcription start site.
      Although the isolated E1 element responds to glucose, inclusion of either of two
      AT-rich sequences, A1 or A2/C1 on either side of E1, results in dramatic
      synergistic activation. Inclusion of A2/C1 also increases the response to
      glucose. The A2-E1-A1 region alone, however, does not explain all of the activity
      of the human insulin promoter in cultured islets, and other transcriptionally
      important elements likely to contribute to the glucose response as well.

PMID- 8567639
TI  - On the mechanism of hyperacidification in lemon. Comparison of the vacuolar H(+)
      ATPase activities of fruits and epicotyls.
AB  - Lemon fruit vacuoles acidify their lumens to pH 2.5, 3 pH units lower than
      typical plant vacuoles. To study the mechanism of hyperacidification, the
      kinetics of ATP-driven proton pumping by tonoplast vesicles from lemon fruits and
      epicotyls were compared. Fruit vacuolar membranes. H+ pumping by epicotyl
      membranes was chloride-dependent, stimulated by sulfate, and inhibited by the
      classical vacuolar ATPase (V-ATPase) inhibitors nitrate, bafilomycin, N
      ethylmaleimide, and N,N'-dicyclohexylcarbodiimide. In addition, the epicotyl H+
      pumping activity was inactivated by oxidation was reversed by dithiothreitol.
      Cold inactivation of the epicotyl V-ATPase by nitrate ( > or = 100 mM) was
      correlated with the release of V1 complexes from the membrane. In contrast, H+
      pumping by the fruit tonoplast-enriched membranes was chloride-independent,
      largely insensitive to the V-ATPase inhibitors, and resistant to oxidation.
      Unlike the epicotyl inhibitors, and resistant to oxidation. Unlike the epicotyl
      H(+)-ATPase, the fruit H(+)-ATPase activity was partially inhibited by 200 microM
      vanadate. Cold inactivation treatment failed to inhibit H+ pumping activity of
      the fruit membranes, even though immunoblasts showed that V1 complexes were
      released from the membrane. However, cold inactivation doubled the percent
      inhibition by 200 microM vanadate from 30% to 60%. These results suggest the
      presence of two H(+)-ATPases in the fruit preparation: a V-ATPase and an
      unidentified vanadate-sensitive H(+)-ATPase. Attempts to separate the two
      activities in their native membranes on linear sucrose density density gradients
      were unsuccessful. However, following detergent-solubilization and centrifugation
      on a glycerol density gradient, the two ATPase activities were resolved: a
      nitrate-sensitive V-type ATPase that is also partially inhibited by 200 microM
      vanadate, and an apparently novel vanadate-sensitive ATPase that is also
      partially inhibited by nitrate.

PMID- 8567640
TI  - Membrane topology of the human Na+/glucose cotransporter SGLT1.
AB  - The membrane topology of the human Na+/glucose cotransporter SGLT1 has been
      probed using N-glycosylation scanning mutants and nested truncations. Functional
      analysis proved essential for establishment of signal-anchor topology. The
      resultant model diverges significantly from previously held suppositions of
      structure based primarily on hydropathy analysis. SGLT1 incorporates 14 membrane
      spans. The N terminus resides extracellularly, and two hydrophobic regions form
      newly recognized membrane spans 4 and 12; the large charged domain near the C
      terminus is cytoplasmic. This model was evaluated further using two advanced
      empirically-based algorithms predictive of transmembrane helices. Helix ends were
      predicted using thermo-dynamically-based algorithms known to predict x-ray
      crystallographically determined transmembrane helix ends. Several considerations
      suggest the hydrophobic C terminus forms a 14th transmembrane helix,
      differentiating the eukaryotic members of the SGLT1 family from bacterial
      homologues. Our data inferentially indicate that these bacterial homologues
      incorporate 13 spans, with an extracellular N terminus. The model of SGLT1
      secondary structure and the predicted helix ends signify information prerequisite
      for the rational design of further experiments on structure/function
      relationships.

PMID- 8567642
TI  - Intracellular zinc movement and its effect on the carbohydrate metabolism of
      isolated rat hepatocytes.
AB  - The effect of zinc ions on carbohydrate metabolism and intracellular Zn2+ was
      studied in hepatocytes from fed rats. The addition of ZnCl2 to the medium led to
      an almost 3-fold increase in lactate production and an increase in net glucose
      production of about 50%. Half-maximal rates occurred at about 40 microM ZnCl2.
      These effects were not seen with Mn2+, Co2+, or Ni2+ up to 80 microM, whereas
      Cu2+ at 80 microM and Cd2+ or Pb2+ at 8 microM exhibited similar effects as 80
      microM ZnCl2. Changes in intracellular Zn2+ were followed by single cell
      epifluorescence using zinquin as a specific probe. Intracellular free Zn2+ in
      isolated hepatocytes was 1.26 +/- 0.27 microM, and the addition of ZnCl2 led to a
      concentration-dependent increase in epifluorescence. CdCl2 or PbCl2 at 8 microM
      was as potent as ZnCl2 at 20-80 microM, whereas NiCl2 at 80 microM was without
      effect. ZnCl2 completely abolished the inhibition of glycolysis by glucagon
      (cAMP). Glucagon led to a pronounced drop in cytosolic Zn2+. Both glucagon and
      zinc stimulated glycogenolysis by increasing the phosphorylation of glycogen
      phosphorylase but acted oppositely on glycolysis. Zinc overcame the inactivation
      of pyruvate kinase by glucagon without changing the hormone-induced protein
      phosphorylation. The antagonistic action of zinc and cAMP on glycolysis together
      with the rapid and marked decrease in free zinc concentration induced by glucagon
      (cAMP) may indicate an as yet unknown role of zinc as an important mediator of
      regulation of carbohydrate metabolism.

PMID- 8567641
TI  - The sequence Glu1811-Lys1818 of human blood coagulation factor VIII comprises a
      binding site for activated factor IX.
AB  - In previous studies have shown that the interaction between factor IXa and VIII
      involves the light chain of factor VIII and that this interaction inhibited by
      the monoclonal antibody CLB-CAg A against the factor VIII region Gln1778-Asp1840
      (Lenting, P.J., Donath, M.J.S.H., van Mourik, J.A., and Mertens, K. (1994) J.
      Biol. Chem. 269, 7150-7155). Employing distinct recombinant factor VIII
      fragments, we now have localized the epitope of this antibody more precisely
      between the A3 domain residues Glu1801 and Met1823. Hydropathy analysis indicated
      that this region is part of a major hydrophilic exosite within the A3 domain. The
      interaction of factor IXa with this exosite was studied by employing overlapping
      synthetic peptides encompassing the factor VII region Tyr1786-Ala1834. Factor IXa
      binding was found to be particularly efficient to peptide corresponding to the
      factor VIII sequences Lys1804-Lys1818 and Glu1811-Gln1820. The same peptides
      proved effective in binding antibody CLB-CAg A. Further analysis revealed that
      peptides Lys1804-Lys1818 and Glu1811-Gln1820 interfere with binding of factor IXa
      to immobilized factor VIII light chain (Ki approximately 0.2 mM and 0.3 mM,
      respectively). Moreover, these peptides inhibit factor X activation by factor IXa
      in the presence of factor VIIIa (Ki approximately 0.2 mM and 0.3 mM,
      respectively) but not in its absence. Equilibrium binding studies revealed that
      these two peptides bind to the factor IX zymogen and its activated form, factor
      IXa, with the same affinity (apparent Kd approximately 0.2 mM), whereas the
      complete factor VIII light chain displays preferential binding to factor IXa. In
      conclusion, our results demonstrate that peptides consisting of the factor VIII
      light chain residues Lys1804-Lys1818 and Glu1811-Gln1820 share a factor IXa
      binding site that is essential for the assembly of the factor X-activating factor
      IXa-factor VIIIa complex. We propose that the overlapping sequence Glu1811
      Lys1818 comprises the minimal requirements for binding to activated factor IX.

PMID- 8567643
TI  - Identification of the site in the substance P (NK-1) receptor for modulation of
      peptide binding by sulfhydryl reagents.
AB  - Substance P (SP) is a peptide neurotransmitter that is involved in multiple
      responses in both the central and the peripheral nervous systems through a G
      protein-coupled contains a number of conserved cysteine residues. To localize and
      identify the cysteine residues that participate in receptor binding, intact
      Chinese hamster ovary cells expressing the SP receptor were treated with various
      sulfhydryl reagents and the effect of these reagents on radioiodinated SP binding
      affinity and dissociation rate was determined. We used a series of amphiphilic
      maleimide derivatives in which the reactive maleimide group penetrates to
      different depths within the plane of membrane. Only the maleimide derivatives
      with intermediate chain lengths modified receptor binding properties, indicating
      that the reactive sulfhydryl group is located within a transmembrane domain of
      the receptor close (within 1.7 nm) to the extracellular border. Since peptide
      binding to a mutant receptor C199S, in which Cys-199 was replaced by a serine,
      was found to be insensitive to modulation by sulfhydryl reagents, this reactive
      sulfhydryl group is on Cys-199 of the receptor. Receptor occupancy by SP protects
      Cys-199 from modification and thus this residue is either located at or
      conformationally linked to the SP binding site.

PMID- 8567644
TI  - Nucleotide vesicular transporter of bovine chromaffin granules. Evidence for a
      mnemonic regulation.
AB  - The nucleotide vesicular transport has been studied with the fluorescent
      substrate analogues, the (1,N6-ethenoadenosine) nucleotides. The transport
      experiments were carried out with granular preparations from bovine adrenal
      medulla, and epsilon-ATP, epsilon-ADP, and epsilon-AMP were quantified after
      separation by high performance liquid chromatography. The granular concentration
      increase of all three nucleotides was time-dependent. The concentration
      dependence of epsilon-nucleotide transport to chromaffin granules did not follow
      the Michaelis-Menten kinetics and presented a similar three-step curve with
      cooperativity. This shape can be considered to be the result of the addition of
      three sigmoidal curves with their corresponding kinetic parameters. epsilon-ATP
      exhibited K values of 0.25, 1, and 3 mM and Vmax values of 0.02, 0.04 and 0.19
      nmol.min-1.mg of protein-1, for the first, second, and third curves for each
      step, respectively. epsilon-ADP exhibited K values of 0.15, 0.9, and 3.6 mM and
      Vmax values of 0.025, 0.035, and 0.3 nmol.min-1.mg of protein-1, respectively for
      the first, second, and third curves. epsilon-AMP exhibited K values of 0.2, 1.2,
      and 3.2 mM, and Vmax values of 0.01, 0.04, and 0.055 nmol.min-1.mg of protein-1,
      also for the first to third steps. The Hill numbers for epsilon-ATP, epsilon-ADP,
      and epsilon-AMP were not constant but a function of the transport saturation. The
      nonhydrolyzable ATP analogues AMPPNP, ATP gamma S, and ADP beta S were activators
      of epsilon-nucleotide transport at concentrations under 1 mM and inhibitors at
      higher concentrations. Atractyloside and N-ethylmaleimide partially inhibited the
      nucleotide granular transport. High extragranular ATP concentrations specifically
      induced the exit of the previously transporter granular epsilon-ATP.

PMID- 8567645
TI  - Strand displacement synthesis of the long terminal repeats by HIV reverse
      transcriptase.
AB  - According to the current model for retroviral replication, strand displacement of
      the long terminal repeat (LTR) is a necessary step during plus strand DNA
      synthesis in vivo. We have investigated the ability of human immunodeficiency
      virus reverse transcriptase (HIV-RT) to synthesize in vitro over a 634-nucleotide
      HIV LTR DNA template, having or lacking a single full-length DNA downstream
      primer. The presence of the downstream primer resulted in an approximately 12
      fold reduction in the rate of upstream primer elongation. Addition of Escherichia
      coli single-stranded binding protein (SSB) or human replication protein A (RP-A)
      enhanced strand displacement synthesis; however, addition of HIV nucleocapsid
      protein (NC) did not. The presence of excess single-stranded DNA complementary to
      the downstream primer did not stimulate displacement synthesis. Interestingly, we
      observed that the elongating upstream primer could readily transfer to this DNA.
      This observation suggests that recombination is favored during strand
      displacement synthesis in vivo.

PMID- 8567646
TI  - Reconstitution of ceruloplasmin by the Cu(I)-glutathione complex. Evidence for a
      role of Mg2+ and ATP.
AB  - The copper-glutathione complex (Cu(I)-GSH) efficiently acted in vitro as the
      source of Cu(I) in the reconstitution of apoceruloplasmin. Copper was found to
      reinstate in the various sites in a multistep process, with metal entry into the
      protein in a first phase, and a second step involving conformational changes of
      the protein leading to the recovery of the native structural and functional
      properties. This latter phase was found to be strongly facilitated by Mg2+ or
      Ca2+ and by ATP. Both Mg2+ and ATP had to be present for optimal reconstitution.
      These results may shed some light on the mechanisms governing the biosynthesis of
      ceruloplasmin in vivo. Cu(I)-GSH was the only complex able to reconstitute
      ceruloplasmin at neutral pH. Glutathione may thus function to shuttle the metal
      from the membrane copper pump, as the Wilson disease ATPase, and ceruloplasmin in
      the secretory compartments of the cell. The finding that ceruloplasmin acquires
      the native conformation after metal entry through a complex pathway triggered by
      Mg2+ and ATP suggests that they may act as physiological modulators of this
      process in vivo.

PMID- 8567647
TI  - Transient interactions between collagen-tailed acetylcholinesterase and sulfated
      proteoglycans prior to immobilization on the extracellular matrix.
AB  - Heparin is capable of solubilizing a subset of collagen-tailed (A12)
      acetylcholinesterase (AChE) molecules from skeletal basal lamina (Rossi, S. G.,
      and Rotundo, R. L. (1993) J. Biol. Chem. 268, 19152-19159). In the present study,
      we used tissue-cultured quail myotubes to show that, like adult fibers, neither
      heparin- nor high salt-containing buffers detached AChE molecules from cell
      surface clusters. Prelabeling clustered AChE molecules with anti-AchE monoclonal
      antibody 1A2 followed by incubation in heparin-containing medium showed that
      there was no reduction in the number or size of preexisting AChE clusters. In
      contrast, incubation of myotubes with culture medium containing heparin for up to
      4 days reversibly blocked the accumulation of new cell-surface AChE molecules
      without affecting the rate of AChE synthesis or assembly. Newly synthesized A12
      AChE becomes tightly attached to the extracellular matrix following
      externalization. However, in the presence of heparin, blocking the initial
      interactions between A12 AChE and the extracellular matrix results in release of
      AChE into the medium with a t1/2 of approximately 3 h. Together, these results
      suggest that once A12 AChE is localized on the cell surface, initially attached
      via electrostatic interactions, additional factors or events are responsible for
      its selective and more permanent retention on the basal lamina.

PMID- 8567648
TI  - Pore formation by the cytotoxic islet amyloid peptide amylin.
AB  - Amylin is a 37-amino acid cytotoxic constituent of amyloid deposits found in the
      islets of Langerhans of patients with type II diabetes. Extracellular
      accumulation of this peptide results in damage to insulin-producing beta cell
      membranes and cell death. We report here that at cytotoxic concentrations, amylin
      forms voltage-dependent, relatively nonselective, ion-permeable channels in
      planar phospholipid bilayer membranes. Channel formation is dependent upon lipid
      membrane composition, ionic strength, and membrane potential. At 1-10 microM,
      cytotoxic human amylin dramatically increases the conductance of lipid bilayer
      membranes, while non-cytotoxic rat amylin does not. We suggest that channel
      formation may be the mechanism of cytotoxicity of human amylin.

PMID- 8567649
TI  - Identification of a nucleolin binding site in human topoisomerase I.
AB  - DNA topoisomerase I (topo I) is involved in the regulation of DNA supercoiling,
      gene transcription, and rDNA recombination. However, little is known about
      interactions between topo I and other nuclear proteins. We used affinity
      chromatography with a topo I fusion protein to screen U-937 leukemic cell
      extracts and have identified nucleolin as a topo I-binding protein.
      Coimmunoprecipitation and other studies demonstrate that the interaction between
      topo I and nucleolin is direct. Furthermore, deletion analyses have identified
      the 166-210-amino acid region of topo I as sufficient for the interaction with
      nucleolin. Since nucleolin has been implicated in nuclear transport and in a
      variety of transcriptional processes, the interaction with topo I may relate to
      the cellular localization of topo I or to the known role of this topoisomerase in
      transcription.

PMID- 8567650
TI  - Promoter selectivity of Escherichia coli RNA polymerase E sigma 70 and E sigma 38
      holoenzymes. Effect of DNA supercoiling.
AB  - The functional specificity was compared between two sigma factors, sigma 70 (the
      major sigma at exponentially growing phase) and sigma 38 (the essential sigma at
      stationary growth phase), of Escherichia coli RNA polymerase. The core enzyme
      binding affinity of sigma 38 was less than half the level of sigma 70 as measured
      by gel filtration column chromatography or by titrating the concentration of
      sigma required for the maximum transcription in the presence of a fixed amount of
      core enzyme. In addition, the holoenzyme concentration required for the maximum
      transcription of a fixed amount of templates was higher for E sigma 38 than E
      sigma 70. The transcription by E sigma 38 was, however, enhanced with the use of
      templates with low superhelical density, in good agreement with the decrease in
      DNA superhelicity in the stationary growth phase. We thus propose that the
      selective transcription of stationary-specific genes by E sigma 38 holoenzyme
      requires either a specific reaction condition(s) or a specific factor(s) such as
      template DNA with low superhelical density.

PMID- 8567652
TI  - Affinity labeling of the 1 alpha,25-dihydroxyvitamin D3 receptor.
AB  - Genomic actions of the calciotropic hormone 1 alpha, 25-dihydroxyvitamin D3
      (1,25(OH)2D3) involves a multistep process that is triggered by the highly
      specific binding of 1,25(OH)2D3 to 1 alpha, 25-dihydroxyvitamin D3 receptor, VDR.
      In order to study this key step in the cascade, we synthesized 1 alpha,25
      dihydroxy[26(27)-3H]vitamin D3-3-deoxy-3 beta-bromoacetate (1,25(OH)2[3H]D3-BE)
      and 1 alpha,25-dihydroxyvitaminD3-3 beta-[1-14C]bromoacetate(1,25(OH)2D3-[14C]BE)
      binding-site directed analogs of 1,25(OH)2D3, and affinity-labeled baculovirus
      expressed recombinant human VDR (with 1,25(OH)2[3H]D3-BE), and naturally
      occurring VDRs in cytosols from calf thymus homogenate and rat osteosarcoma (ROS
      17/2.8) cells (with 1,25(OH)2D3-[14C]BE). In each case, specificity of labeling
      was demonstrated by the drastic reduction in labeling when the incubation was
      carried out in the presence of an excess of nonradioactive 1 alpha,25(OH)2D3.
      These results strongly suggested that 1,25(OH)2[3H]D3-BE and 1,25(OH)2D3-[14C]BE
      covalently modified the 1,25(OH)2D3-binding sites in baculovirus-expressed
      recombinant human VDR and naturally occurring calf thymus VDR and rat
      osteosarcoma VDR, respectively.

PMID- 8567651
TI  - Interleukin-1 increases vacuolar-type H+-ATPase activity in murine peritoneal
      macrophages.
AB  - Maintenance of cytoplasmic pH (pHi) within a narrow physiological range is
      crucial to normal cellular function. This is of particular relevance to
      phagocytic cells within the acidic inflammatory microenvironment where the pHi
      tends to be acid loaded. We have previously reported that a vacuolar-type H(+)
      ATPase (V-ATPase) situated in the plasma membrane of macrophages and poised to
      extrude protons from the cytoplasmic to the extracellular space is an important
      pHi regulatory mechanism within the inflammatory milieu. Since this
      microenvironment is frequently characterized by the influx of cells known to
      release inflammatory cytokines, we performed studies to examine the effect of one
      such mediator molecule, interleukin-1 (IL-1), on pHi regulation in peritoneal
      macrophages. IL-1 caused a time- and dose-dependent increase in macrophage pHi
      recovery from an acute acid load. This effect was specific to IL-1 and was due to
      enhanced plasmalemmal V-ATPase activity. The increased V-ATPase activity by IL-1
      occurred following a lag period of several hours and required de novo protein and
      mRNA synthesis. However, Northern blot analysis revealed that IL-1 did not exert
      its effect via alterations in the levels of mRNA transcripts for the A or B
      subunits of the V-ATPase complex. Finally, stimulation of both cAMP-dependent
      protein kinase and protein kinase C was required for the stimulatory effect of IL
      1 on V-ATPase activity. Thus, cytokines present within the inflammatory milieu
      are able to modulate pHi regulatory mechanisms. These data may represent a novel
      mechanism whereby cytokines may improve cellular function at inflammatory sites.

PMID- 8567653
TI  - Site-directed mutagenesis of the yeast V-ATPase B subunit (Vma2p).
AB  - The B subunit of the vacuolar (H+)-ATPase (V-ATPase) has previously been shown to
      participate in nucleotide binding and to possess significant sequence homology
      with the alpha subunit of the mitochondrial F-ATPase, which forms the major
      portion of the noncatalytic nucleotide binding sites and contributes several
      residues to the catalytic sites of this complex. Based upon the recent x-ray
      structure of the mitochondrial F1 ATPase (Abrahams, J.P., Leslie, A.G., Lutter,
      R., and Walker, J.E. (1994) Nature 370,621-628), site-directed mutagenesis of the
      yeast VMA2 gene has been carried out in a strain containing a deletion of this
      gene. VMA2 encodes the yeast V-ATPase B subunit (Vma2p). Mutations at two
      residues postulated to be contributed by Vma2p to the catalytic site (R381S and
      Y352S) resulted in a complete loss of ATPase activity and proton transport, with
      the former having a partial effect on V-ATPase assembly. Interestingly,
      substitution of Phe for Tyr-352 had only minor effects on activity (15-30%
      inhibition), suggesting the requirement for an aromatic ring at this position.
      Alteration of Tyr-370, which is postulated to be near the adenine binding pocket
      at the noncatalytic sites, to Arg, Phe, or Ser caused a 30-50% inhibition of
      proton transport and ATPase activity, suggesting that an aromatic ring is not
      essential at this position. Finally, mutagenesis of residues in the region
      corresponding to the P-loop of the alpha subunit (H180K, H180G, H180D, N181V)
      also inhibited proton transport and ATPase activity by approximately 30-50%. None
      of the mutations in either the putative adenine binding pocket nor the P-loop
      region had any effect on the ability of Vma2p to correctly fold nor on the V
      ATPase to correctly assemble. The significance of these results for the structure
      and function of the nucleotide binding sites on the B subunit is discussed.

PMID- 8567654
TI  - Regulation of cellular cholesterol efflux by lecithin:cholesterol acyltransferase
      reaction through nonspecific lipid exchange.
AB  - Erythrocyte was found lacking in reactivity to lipid-free apolipoproteins to
      generate pre-beta-high density lipoprotein (HDL) with the cellular lipid and,
      therefore, was used to study cellular cholesterol efflux to plasma lipoproteins
      exclusively by a nonspecific exchange mechanism. Over the range of hematocrit
      from 1-20% (cellular cholesterol pool of 2.5 micrograms per 250 microliters), the
      fractional rate of cellular cholesterol efflux to lipoprotein was constant, and,
      therefore, absolute efflux rate was a linear function of the hematocrit of this
      range. In the absence of lecithin:cholesterol acyltransferase (LCAT), the
      cholesterol influx rate from lipoproteins was equal to the efflux rate from
      erythrocyte resulting in no net transfer of cholesterol, with either HDL or low
      density lipoprotein. In the presence of LCAT in the mixture of HDL and
      erythrocyte, cholesterol was esterified exclusively in HDL regardless of the
      origin. When the hematocrit was low and efflux of cellular cholesterol was slower
      than cholesterol esterification, the esterification of cell-originating
      cholesterol did not directly enhance the efflux. With high hematocrit that gives
      faster cholesterol efflux, the efflux was increased directly by the cholesterol
      esterification. On the other hand, the LCAT reaction significantly reduced HDL
      cholesterol influx. The LCAT reaction thus induces substantial net cholesterol
      efflux from erythrocytes through a nonspecific cholesterol exchange mechanism.

PMID- 8567655
TI  - P2 purinergic receptor agonists enhance cAMP production in Madin-Darby canine
      kidney epithelial cells via an autocrine/paracrine mechanism.
AB  - Mechanisms of cross-talk between different classes of signaling molecules are
      inadequately understood. We have used clonal Madin-Darby canine kidney (MDCK-D1)
      epithelial cells as a model system to investigate the effects of extracellular
      nucleotides (e.g. ATP, UTP), which promote increase in activity of several
      phospholipases, on cAMP production. In contrast to observations in some other
      cell systems, ATP and UTP, acting via P2 purinergic receptors, stimulated cAMP
      production in MDCK-D1 cells. At maximally effective concentrations, ATP and UTP
      were not additive with the beta-adrenergic receptor agonist isoproterenol, but
      were synergistic with forskolin in increasing cAMP production, indicating that G
      alpha s is activated by these nucleotides. Additionally, we found that (a)
      nucleotide-induced increases in cAMP were blocked by indomethacin, a
      cyclooxygenase inhibitor, (b) arachidonic acid increased cellular cAMP levels in
      an indomethacin-sensitive fashion, and (c) PGE2, the major metabolite of
      arachidonic acid, stimulated cAMP formation. Overall, our results suggest a
      mechanism by which extracellular nucleotides stimulate release of arachidonic
      acid which is metabolized to PGE2 which, in turn, acts in an autocrine/paracrine
      fashion via prostaglandin receptors to activate G alpha s and increase cAMP.
      Based on the ability of extracellular nucleotides to stimulate the formation and
      release of prostaglandins in MDCK-D1 epithelial and other cells, we hypothesize
      that receptor-mediated prostaglandin release may be a general mechanism that
      regulates cAMP formation in many types of cells.

PMID- 8567656
TI  - The amino-terminal one-third of alpha IIb defines the ligand recognition
      specificity of integrin alpha IIb beta 3.
AB  - The integrin alpha subunits play a major role in the regulation of ligand binding
      specificity. To gain further insight into the regions of the alpha subunits that
      regulate ligand specificity, we have utilized alpha v / alpha IIb chimeras to
      identify regions of alpha IIb that when substituted for the homologous regions of
      alpha v switched the ligand binding phenotype of alpha v beta 3 to that of alpha
      IIb beta 3. We report that the ligand recognition specificity of beta 3 integrins
      is regulated by the amino-terminal one-third of the alpha subunit. Substitution
      of the amino-terminal portion of alpha v with the corresponding 334 residues of
      alpha IIb reconstituted reactivity with both alpha IIb beta 3-specific activation
      dependent (PAC1) and -independent (OPG2) ligand mimetic antibodies in addition to
      small highly specific activation-independent ligands. In contrast, substitution
      of the amino-terminal portion alone or the divalent cation repeats alone were not
      sufficient to change ligand binding specificity. These data in combination with
      previous studies demonstrate that integrin ligand recognition requires
      cooperation between elements in both the alpha and beta subunits and indicate
      that the ligand binding pocket is a structure assembled from elements of both the
      alpha and beta subunits.

PMID- 8567657
TI  - Design of a C/EBP-specific, dominant-negative bZIP protein with both inhibitory
      and gain-of-function properties.
AB  - We have developed a bZIP protein, GBF-F, with both dominant-negative (DN) and
      gain-of-function properties. GBF-F is a chimera consisting of two components: the
      DNA binding (basic) region from the plant bZIP protein GBF-1 (GBF) and a leucine
      zipper (F) designed to preferentially heterodimerize with the C/EBP alpha leucine
      zipper. Biochemical studies show that GBF-F preferentially forms heterodimers
      with C/EBP alpha and thus binds a chimeric DNA sequence composed of the half
      sites recognized by the C/EBP and GBF basic regions. Transient transfections in
      HepG2 hepatoma cells show that both components of GBF-F are necessary for
      inhibition of C/EBP alpha transactivation. When the C/EBP alpha leucine zipper is
      replaced with that of either GCN4 or VBP, the resulting protein can transactivate
      a C/EBP cis-element but is not inhibited by GBF-F, indicating that the
      specificity of dominant-negative action is determined by the leucine zipper. All
      known members of the C/EBP family contain similar leucine zipper regions and are
      inhibited by GBF-F. GBF-F also exhibits gain-of-function properties, since, with
      the essential cooperation of a C/EBP family member, it can transactivate a
      promoter containing the chimeric C/EBP/GBF site. This protein therefore has
      potential utility both as a dominant-negative inhibitor of C/EBP function and as
      an activator protein with novel DNA sequence specificity.

PMID- 8567658
TI  - Reactions of prostaglandin endoperoxide synthase and its compound I with
      hydroperoxides.
AB  - The reactions of native prostaglandin endoperoxide synthase with structurally
      different hydroperoxides have been investigated by using kinetic
      spectrophotometric scan and conventional and sequential mixing stopped-flow
      experiments. The second order rate constants for compound I formation are (5.9 +/
      0.1) x 10(4) M-1 s-1 using t-butyl hydroperoxide as the oxidant, (2.5 +/- 0.1) x
      10(6) M-1 s-1 for ethyl hydroperoxide and (5.1 +/- 0.6) x 10(7) M-1 s-1 for m
      chloroperoxybenzoic acid at pH 7.0, 6.7 +/- 0.2 degrees C, and ionic strength 0.1
      M. Sequential mixing, transient state experiments show for the first time that
      all hydroperoxides reduce compound I in a bimolecular reaction. Ethyl
      hydroperoxide, t-butyl hydroperoxide, and m-chloroperoxybenzoic acid react
      directly with compound I. The natural substrate prostaglandin G2 forms a
      transient complex with compound I before the reduction step occurs. Therefore,
      compound I initially transforms to compound II, not to the compound I-tyrosyl
      radical. Second order rate constants for the reactions of compound I are (2.9 +/-
      0.2) x 10(4) for t-butyl hydroperoxide, (3.5 +/- 0.5) x 10(4) for hydrogen
      peroxide, (4.2 +/- 0.2) x 10(4) for ethyl hydroperoxide, and (4.2 +/- 0.3) x
      10(5) for m-chloroperoxybenzoic acid, all in units of M-1 s-1 and same conditions
      as for compound I formation. The rate of reaction of prostaglandin G2 with
      compound I, calculated from the ratio of kcat to Km obtained from the saturation
      curve, is (1.0 +/- 0.2) x 10(6) M-1 s-1 at 3.0 +/- 0.2 degrees C. Results are
      discussed in the context of the current state of knowledge of the mechanisms of
      the cyclooxygenase and peroxidase reactions of prostaglandin endoperoxide
      synthase.

PMID- 8567659
TI  - Functional expression of subunit IV of Rhodobacter sphaeroides cytochrome b-c1
      complex and reconstitution of recombinant protein with three-subunit core
      complex.
AB  - Subunit IV of Rhodobacter sphaeroides cytochrome b-c1 complex was over-expressed
      in Escherichia coli JM109 cells as a glutathione S-transferase fusion protein
      (GST-RSIV) using the expression vector, pGEX/RSIV. Maximum yield of soluble
      active recombinant fusion protein was obtained from cells harvested 3 h after
      induction of growth at 37 degrees C in LB medium. Subunit IV was released from
      the fusion protein by proteolytic cleavage with thrombin. When subjected to SDS
      polyacrylamide gel electrophoresis, isolated recombinant subunit IV of R.
      sphaeroides cytochrome b-c1 complex. Although the isolated recombinant subunit IV
      is soluble in aqueous solution, it is in a highly aggregated form, with an
      apparent molecular mass of over 1000 kDa. The addition of detergent deaggregates
      the isolated protein, suggesting that the recombinant protein exists as a
      hydrophobic aggregation in aqueous solution. When the three-subunit core
      cytochrome b-c1 complex, purified from RS delta IV-adapted chromatophores
      containing a fraction of the wild type cytochrome b-c1 complex activity, was
      reacted with varying amounts of recombinant subunit IV, the activity increased as
      the subunit IV concentration increased. Maximum activity restoration was reached
      when 1 mol of subunit IV/mol of three-subunit core complex was used. The
      reconstituted cytochrome b-c1 complex is similar to the wild-type complex in
      molecular size, apparent Km for Q2H2, and inhibitor sensitivity, indicating that
      recombinant subunit IV is properly assembled into the active cytochrome b-c1
      complex. A tryptophan residue in subunit IV was found to be involved in the
      interaction with the three-subunit core complex.

PMID- 8567660
TI  - Helix structure and ends of RNA/DNA hybrids direct the cleavage specificity of
      HIV-1 reverse transcriptase RNase H.
AB  - RNA/DNA hybrids in human immunodeficiency virus (HIV) replication are cleaved by
      HIV-1 reverse transcriptase (RT) H in locations determined by hybrid structure.
      Minus strand DNA synthesis is accompanied by cleavage of template viral RNA
      directed by RT positioned at the growing 3' DNA end. Some RNA remains as
      oligomers annealed to the new DNA strand and is cut by RTs positioned at the 5'
      RNA ends. We constructed substrates to the test the hypothesis that internal
      helix structure, rather than strand end structure, drives the RT to position at
      3' DNA and 5' RNA ends. On substrates with an RNA primer recessed on a DNA
      template, the 5' end of the RNA had a dominant role in the determination of RNase
      H cleavage positions. If the 5' end region of the RNA could not anneal, cleavage
      would not occur. Nevertheless, we obtained evidence that helix structure promotes
      the binding of RT to the end of the helical region closest to the 5' RNA/3' DNA
      end. When a DNA primer recessed on an RNA template had a 3' unannealed region,
      cleavage occurred, with RT positioned solely by helical structure at the 5'
      RNA/3' DNA end of the annealed region of the hybrid. Using substrates having RNA
      primers annealed to circular DNA templates, we showed that cleavage can be
      independent of the presence of a DNA 3'end and is directed by the 5' RNA end.
      Overall, the results suggest that the RT initially binds an internal region of
      the hybrid and then is driven in the direction to encounter a 3' DNA or 5' RNA
      end, where it is positioned for catalysts by the strand end. The requirement for
      two modes of RNA cleavage in viral replication and the unexpected requirement for
      the 5' RNA end structure are discussed.

PMID- 8567661
TI  - Specific induction of cell motility on laminin by alpha 7 integrin.
AB  - Laminin, the major glycoprotein of basement membranes, actively supports cell
      migration in development, tissue repair, tumor growth, metastasis, and other
      pathological processes. Previously we have shown that the locomotion of murine
      skeletal myoblasts is specifically and significantly enhanced on laminin but not
      on other matrix proteins. One of the major laminin receptors of myoblasts is the
      alpha 7 beta 1 integrin, which was first described in human MeWo melanoma cells
      and Rugli glioblastoma cells. In order to investigate and directly test the role
      of the alpha 7 integrin in cell migration on laminin, we expressed the murine
      alpha 7B splice variant in human 293 kidney cells and 530 melanoma cells which
      cannot migrate on laminin and are devoid of endogenous alpha 7. Northern blotting
      of the transfected cells showed that the alpha 7 mRNA was expressed efficiently,
      and the protein was detected on the cell surface by immunofluorescence and
      fluorescence-activated cell sorter analysis. Cell motility measurements by
      computer-assisted time-lapse videomicroscopy of the alpha 7-transfected cells
      revealed an 8-10-fold increase in motility on laminin-1 and its E8 fragment, but
      not on fibronectin. Mock-transfected cells did not migrate significantly of alpha
      7-transfected 293 cells through laminin-coated filters in a Boyden chamber assay
      was significantly enhanced in comparison to mock transfected cells. These
      findings prove that alpha 7 integrin expression confers a gain of function-motile
      phenotype to immobile cells and may be responsible for transduction of the
      laminin-induced cell motility.

PMID- 8567662
TI  - Triiodothyronine induces the transcription of the uncoupling protein gene and
      stabilizes its mRNA in fetal rat brown adipocyte primary cultures.
AB  - Confluent fetal rat brown adipocytes in primary culture showed an almost
      undetectable level of uncoupling protein (UCP) mRNA and a low mitochondrial
      content of functional UCP. Treatment of confluent cells with 10 nM
      triiodothyronine in a serum-free medium, in the absence of noradrenergic
      stimulation, increased the amount of UCP mRNA in a time-dependent manner. This
      effect was due to an increased UCP gene transcription rate and UCP mRNA
      stabilization, resulting in a higher content of immunoreactive mitochondrial UCP
      and functional UCP (detected by its ability to bind GDP). Thus, triiodothyronine
      might play a significant physiological role in the UCP expression throughout
      fetal development, when brown adipose tissue starts to differentiate and UCP is
      primarily expressed.

PMID- 8567663
TI  - Activation of a high affinity Gi protein-coupled plasma membrane receptor by
      sphingosine-1-phosphate.
AB  - Sphingosine-1-phosphate (SPP) has attracted much attention as a possible second
      messenger controlling cell proliferation and motility and as an intracellular
      Ca(2+)-releasing agent. Here, we present evidence that SPP activates a G protein
      coupled receptor in the plasma membrane of various cells, leading to increase in
      cytoplasmic Ca2+ concentration ([Ca2+]i), inhibition of adenylyl cyclase, and
      opening of G protein-regulated potassium channels. In human enbryonic kidney
      (HEK) cells, SPP potently (EC50, 2 nM) and rapidly increased [Ca2+]i in a
      pertussis toxin-sensitive manner. Pertussis toxin-sensitive increase in [Ca2+]i
      was also observed with sphingosylphosphorylcholine (EC50, 460 nM), whereas other
      sphingolipids, including ceramide-1-phosphate, N-palmitoyl-sphingosine,
      psychosine, and D-erythro-sphingosine at micromolar concentrations did not or
      only marginally increased [Ca2+]i. Furthermore, SPP inhibited forskolin
      stimulated cAMP accumulation in HEK cells and increased binding of guanosine 5'3
      O-(thio) triphosphate to HEK cell membranes. Rapid [Ca2+]i responses were also
      observed in human transitional bladder carcinoma (J82) cells, monkey COS-1 cells,
      mouse NIH 3T3 cells, Chinese hamster ovary (CHO-K1) cells, and rat C6 glioma
      cells, whereas human HL-60 leukemia cells and human erythroleukemia cells failed
      to respond to SPP. In guinea pig atrial myocytes, SPP activated Gi protein
      regulated inwardly rectifying potassium channels. Activation of these channels
      occurred strictly when SPP was applied at the extracellular face of atrial
      myocyte plasma membrane as measured in cell-attached and inside-out patch clamp
      current recordings. We conclude that SPP, in addition to its proposed direct
      action on intracellular Ca2+ stores, interacts with a high affinity Gi protein
      coupled receptor in the plasma membrane of apparently many different cell types.

PMID- 8567664
TI  - Nitrate and nitrate are transported by different specific transport systems and
      by a bispecific transporter in Chlamydomonas reinhardtii.
AB  - Nitrate transport mutants from Chlamydomonas reinhardtii and strains derived from
      them upon transformation with plasmids containing the C. reinhardtii nar2/Nrt2;1
      or nar2/Nrt2;2 genes have been used to study nitrate and nitrite transport
      systems. Mutants lacking nitrate assimilation clustered genes showed a high
      affinity nitrite transporter activity (system 3), which was subject to ammonium
      inhibition and appeared to be independent of a functional nar2 gene.
      Transformants carrying nar2/Nrt2;2 recovered a high affinity nitrate transporter
      activity (system 2) and showed nitrite transport activities with properties
      similar to those in nonrecovered high affinity nitrate transporter activity
      (system 1) together with a considerably enhanced nitrite transport activity.
      Nitrite transport mediated by system 1 was very sensitive to inhibition by
      nitrate at microM concentrations. Results strongly suggest that three nitrate
      assimilation related high affinity transport systems operate in C. reinhardtii:
      one specific for nitrite, a second one encoded by nar2/Nrt2;2 specific for
      nitrate, and another one encoded by nar2/Nrt2;1, which is bispecific for these
      two anions.

PMID- 8567665
TI  - Comparison of primary charge separation in the photosystem II reaction center
      complex isolated from wild-type and D1-130 mutants of the cyanobacterium
      Synechocystis PCC 6803.
AB  - We compare primary charge separation in a photosystem II reaction center
      preparation isolated from a wild-type (WT) control strain of the cyanobacterium
      Synechocystis sp. PCC 6803 and from two site-directed mutants of Synechocystis in
      which residue 130 of the D1 polypeptide has been changed from a glutamine to
      either a glutamate (mutant D1-Gln130Glu), as in higher plant sequences, or a
      leucine residue (mutant D1-Gln130Leu). The D1-130 residue is thought to be close
      to the pheophytin electron acceptor. We show that, when P680 is photoselectively
      excited, the primary radical pair state P680+Ph- is formed with a time constant
      of 20-30 ps in the WT and both mutants; this time constant is very similar to
      that observed in Pisum sativum (a higher plant). We also show that a change in
      the residue at position D1-130 causes a shift in the peak of the pheophytin Qx
      band. Nanosecond and picosecond transient absorption measurements indicate that
      the quantum yield of radical pair formation (phi RP), associated with the 20-30
      ps component, is affected by the identify of the D1-130 residue. We find that,
      for the isolated photosystem II reaction center particle, phi RP higher plant >
      phi RP D1-Gln130Glu mutant > phi RP WT > phi RP D1-Gln130Leu mutant. Furthermore,
      the spectroscopic and quantum yield differences we observe between the WT
      Synechocystis and higher plant photosystem II, seem to be reversed by mutating
      the D1-130 ligand so that it is the same as in higher plants. This result is
      consistent with the previously observed natural regulation of quantum yield in
      Synechococcus PS II by particular changes in the D1 polypeptide amino acid
      sequence (Clark, A.K., Hurry, V. M., Gustafsson, P. and Oquist, G. (1993) Proc.
      Natl. Acad. Sci. U.S.A. 90, 11985-11989).

PMID- 8567667
TI  - Cytochrome c oxidase subunit VIIa liver isoform. Characterization and
      identification of promoter elements in the bovine gene.
AB  - Cytochrome c oxidase subunit VIIa is specified by two nuclear genes, one (COX7AH)
      producing a heart/muscle-specific isoform and the other (COX7AL) a form expressed
      in all tissues. We have isolated both genes to examine their transcriptional
      regulation. Here, we characterize the core promoter of COX7AL and show that a 92
      base pair region flanking the 5'-end promotes most of the activity of this gene.
      The 92-bp basal promoter contains sites for the nuclear respiratory factors NRF-1
      and NRF-2, which have been shown to contribute to the transcription of a number
      of nuclear genes involved in mitochondrial respiratory activity, and also at
      least four Sp1 motifs. We show that both the NRF-1 and NRF-2 binding sites are
      functional in COX7AL and present evidence suggesting that interaction between the
      NRF-1 site and an upstream element contributes to expression.

PMID- 8567666
TI  - Partial reversal of multidrug resistance in human breast cancer cells by an N
      myristoylated protein kinase C-alpha pseudosubstrate peptide.
AB  - The predominant characteristics of multidrug resistant (MDR) cancer cells are
      broad spectrum resistance to chemotherapeutic agents and a pronounced defect in
      intracellular accumulation of the drugs, in association with overexpression of
      the drug efflux pump P-glycoprotein. Protein kinase C (PKC) phosphorylates the
      linker region of P-glycoprotein. Evidence has been presented that the isozyme PKC
      alpha may contribute to the drug resistance phenotype of human breast cancer MCF7
      MDR cells, PKC-alpha is markedly overexpressed in MCF7-MDR cells, and artificial
      overexpression of PKC-alpha in MCF7 constructs that overexpress P-glycoprotein
      significantly enhances the MDR phenotype of the cells in association with
      increased P-glycoprotein phosphorylation. Verapamil, cyclosporin A, and a number
      of other agents that compete with cytotoxic drugs for binding sites on P
      glycoprotein can potently reverse MDR, but this is accompanied by severe toxicity
      in vivo. In this report, we demonstrate that an N-myristoylated peptide that
      contains a sequence corresponding to the pseudosubstrate region of PKC-alpha (P1)
      partially reverses multidrug resistance in MCF7-MDR cells by a novel mechanism
      that involves inhibition of PKC-alpha. P1 and two related PKC inhibitory N
      myristoylated peptides restored intracellular accumulation of chemotherapeutic
      drugs in association with inhibition of the phosphorylation of three PKC-alpha
      substrates in MCF7-MDR cells: PKC-alpha, Raf-1 kinase, and P-glycoprotein. A
      fourth N-myristoylated peptide substrate analog of PKC, P7, did not affect drug
      accumulation in the MCF7-MDR cells and failed to inhibit the phosphorylation of
      the PKC-alpha substrates. The effects of P1 and verapamil on drug accumulation in
      MCF7-MDR cells were additive. P1 did not affect P-glycoprotein expression. MCF7
      MDR cells were not cross-resistant to P1, which suggest that the peptide was not
      transported by P-glycoprotein. Furthermore, P1 was distinguished from MDR
      reversal agents such as verapamil and cyclosporin A by its inability to inhibit
      [3H]azidopine photoaffinity labeling of P-glycoprotein. P1 actually increased
      [3H] azidopine photoaffinity labeling of P-glycoprotein in MCF7-MDR cells,
      providing evidence that the effects of P1 on P-glycoprotein in MCF7-MDR cells are
      not restricted to inhibition of the phosphorylation of the pump. P1 may provide a
      basis for developing a new generation of MDR reversal agents that function by a
      novel mechanism that involves inhibition of PKC-alpha-catalyzed P-glycoprotein
      phosphorylation.

PMID- 8567668
TI  - Glucose stimulates the activity of the guanine nucleotide-exchange factor eIF-2B
      in isolated rat islets of Langerhans.
AB  - Over short time periods glucose controls insulin biosynthesis predominantly
      through effects on preexisting mRNA. However, the mechanisms underlying the
      translational control of insulin synthesis are unknown. The present study was
      carried out to determine the effect of glucose on the activity and/or
      phosphorylation status of eukaryotic initiation and elongation factors in islets.
      Glucose was found to increase the activity of the guanine nucleotide-exchange
      factor eIF-2B over a rapid time course (within 15 min) and over the same range of
      glucose concentrations as those that stimulate insulin synthesis (3-20 mM). A
      nonmetabolizable analogue of glucose (mannoheptulose), which does not stimulate
      insulin synthesis, failed to activate eIF-2B. The best characterized mechanism
      for modulating eIF-2B activity involves changes in the phosphorylation of the
      alpha-subunit of its substrate eIF-2. However, in islets, no change in eIF-2
      alpha phosphorylation was seen under conditions where eIF-2B activity was
      increased, implying that glucose regulates eIF-2B via an alternative pathway.
      Glucose also did not affect the phosphorylation states of three other regulatory
      translation factors. These are the cap-binding factor eIF-4E, 4E-binding protein
      1, and elongation factor eEF-2, which do not therefore seem likely to be involved
      modulating the translation of the preproinsulin mRNA under these conditions.

PMID- 8567670
TI  - Rearrangements of the fibrin network and spatial distribution of fibrinolytic
      components during plasma clot lysis. Study with confocal microscopy.
AB  - Binding of components of the fibrinolytic system to fibrin is important for the
      regulation of fibrinolysis. In this study, decomposition of the fibrin network
      and binding of plasminogen and plasminogen activators (PAs) to fibrin during
      lysis of a plasma clot were investigated with confocal microscopy using
      fluorescein-labeled preparations of fibrinogen, plasminogen, tissue-type PA (t
      PA), and two-chain urokinase-type PA (tcu-PA). Lysis induced by PAs present
      throughout the plasma clot was accompanied by a gradual loss of fibrin content of
      fibers and by accumulation of plasminogen onto the fibers. Two sequential phases
      could be distinguished: a phase of prelysis, during which the fibrin network
      remained immobile, and a phase of final lysis, during which fibers moved with a
      tendency to shrink and eventually disappeared. The two phases occurred
      simultaneously but in different locations when lysis was induced by PAs present
      in the plasma surrounding the clot. The zone of final lysis was located within a
      5-8 microns superficial layer, where fibers were mobile, a surface-associated
      fibrin agglomerates appeared. Plasminogen accumulated in these agglomerates up to
      30-fold as compared with its concentration in the outer plasma. t-PA was also
      highly concentrated in the agglomerates, and tcu-PA bound to them slightly. The
      zone of prelysis, where plasminogen was moderately accumulated on the immobile
      fibers, was located deeper in the clot. This zone was much thinner in the case of
      t-PA-induced lysis than in the case of tcu-PA-induced lysis, reflecting the
      difference in penetration of the two PAs into the clot. We conclude that under
      conditions of diffusional transport of fibrinolytic enzymes from outside a plasma
      clot, extensive lysis is spatially restricted to a zone not exceeding 5-8 microns
      from the clot surface. In this zone the structure of the fibrin network undergoes
      significant changes, and strikingly high accumulation of fibrinolytic components
      takes place.

PMID- 8567669
TI  - Human cathepsin O2, a matrix protein-degrading cysteine protease expressed in
      osteoclasts. Functional expression of human cathepsin O2 in Spodoptera frugiperda
      and characterization of the enzyme.
AB  - Cathepsin O2, a human cysteine protease predominantly present in osteoclasts, has
      been functionally expressed in Spodoptera frugiperda Sf9 cells using the
      Autographa californica nuclear polyhedrosis virus. Following in vitro activation
      at pH 4.0 with pepsin, active enzyme with an apparent molecular weight of 29,000
      was obtained. N-terminal sequencing revealed the typical processing site for
      cysteine proteases of the papain family with a proline in the position adjacent
      to the N-terminal alanine residue. The S2P2 subsite specificity of human
      cathepsin O2 is similar to cathepsin S but distinguished from cathepsins L and B.
      Similar to cathepsin S, cathepsin O2 is characterized by a bellshaped pH activity
      profile and is stable at pH 6.5 for 30 min at 37 degrees C. Cathepsin O2 is
      further distinguished by its potent collagenolytic activity against Type I
      collagen between pH 5 and 6, and elastinolytic activity against insoluble elastin
      at pH 7.9. Its capacity to efficiently degrade Type I collagen and its high
      expression in osteoclasts suggest that cathepsin O2 may play a major role in
      human osteoclastic bone resorption.

PMID- 8567671
TI  - The mutation Gly142-->Glu in human lipoprotein lipase produces a missorted
      protein that is diverted to lysosomes.
AB  - While the molecular characterization of lipoprotein lipase (LPL) activation is
      progressing, the intracellular processing, transport, and secretion signals of
      LPL are still poorly known. The aim of this paper is to study are involvement of
      glycine 142 in LPL secretion and to elucidate the intracellular destination of
      the altered protein that remains inside the cell. We mutated the human LPL cDNA
      by site-directed mutagenesis in order to produce the G142e hLPL in which the
      glycine 142 was replaced by a glutamic acid. The wild type human LPL (WT hLPL)
      and the mutant G142E hLPL were expressed by transient transfection in COS1 cells.
      Using Western blot assays we identified a single band that had the same molecular
      weight for both proteins. However, Western blots of culture media did not reveal
      any specific band for the mutant protein, and ELISA experiments showed that the
      extracellular mass of the mutant LPL was only 25% of the WT protein, indicating
      defective secretion of the altered enzyme. Heparin increased LPL secretion in the
      case of the WT hLPL but did not have any stimulatory effect when acting on G142E
      hLPL-transfected cells. However, heparin-Sepharose chromatography revealed that
      both proteins presented the same heparin affinity. Metabolic labeling and
      radioimmunoprecipitation studies showed that both the WT and the mutant hLPL
      intracellular levels decreased upon chase time. Furthermore, leupeptin had a
      greater effect on the intracellular level of the mutant enzyme, thus indicating
      its higher intracellular degradation. Immunofluorescent studies using confocal
      microscopy indicated high colocalization of the LPL labeling and the Lamp1
      lysosomal labeling in G142E hLPL-expressing cells. This result was confirmed
      using immunoelectron microscopy, which in addition showed gold labeling in Golgi
      stacks. This finding together with experiments performed with endoglycosidase H
      digestion of immunoprecipitated radiolabeled LPL, indicated that the mutant
      enzyme entered the Golgi compartment. The results reported in this paper show
      that the G142E hLPL is not efficiently secreted to the extracellular medium, but
      it is missorted to lysosomes for intracellular degradation. This finding suggests
      that lysosomal missorting might be a mechanism of cell quality control of
      secreted LPL.

PMID- 8567673
TI  - Coenzyme A-independent monoacylglycerol acyltransferase from rat intestinal
      mucosa.
AB  - Rat intestinal mucosa contains high diacylglycerol-synthesizing activity
      (monoacylglycerol acyltransferase (MGAT) activity) due to monoacylglycerol and
      fatty acid, independently of coenzyme A and ATP. MGAT activity was purified from
      rat intestinal mucosa by successive chromatography separations on DEAE-cellulose,
      CM- Sephadex, and anti-IgG-Sepharose against rat pancreatic lipase. The enzyme
      was electrophoretically homogeneous, and its molecular weight was 49,000, which
      is identical with that of rat pancreatic lipase. Immunoblotting analysis with
      antibody against rat pancreatic lipase showed one immunoreactive protein with an
      estimated molecular weight of 49,000. The activity of the purified enzyme was
      completely inhibited by addition of the antibody. Using immunocytochemical
      techniques, it was found that immunoreactive protein against rat pancreatic
      lipase was uniformly distributed within the absorptive cells of the intestine but
      was absent from the microvillar membrane. The MGAT activity of intestinal mucosal
      homogenate was inhibited by about 65% by addition of antibody against rat
      pancreatic lipase. Trioleoylglycerol- and dioleoylglycerol-hydrolyzing activities
      of the purified enzyme and pancreatic lipase were inhibited by addition of
      intestinal mucosa extract. These results suggest that pancreatic lipase is
      present in intestinal absorptive cells and that it may contribute to resynthesis
      of diacylglycerol from monoacylglycerol and fatty acids in these cells.

PMID- 8567672
TI  - Identification of a peroxisome proliferator-responsive element upstream of the
      human peroxisomal fatty acyl coenzyme A oxidase gene.
AB  - Peroxisome proliferators cause a rapid and coordinated transcriptional activation
      of genes encoding the enzymes of the peroxisomal beta-oxidation pathway in rats
      and mice. Cis-acting peroxisome proliferator responsive elements (PPREs) have
      been identified in the 5'-flanking region of H202-producing rat acyl-CoA oxidase
      (ACOX) gene and in other genes inducible by peroxisome proliferators. To gain
      more insight into the purported nonresponsiveness of human liver cells to
      peroxisome volume density and in the activity of the beta-oxidation enzyme
      system, we have previously cloned the human ACOX gene, the first and rate
      limiting enzyme of the peroxisomal beta-oxidation system. We now present
      information on a regulatory element for the peroxidase proliferator-activated
      receptor (PPAR)/retinoid X receptor (RXR) heterodimers. The PPRE, consists of
      AGGTCA C TGGTCA, which is a direct repeat of hexamer half-sites interspaced by a
      single nucleotide (DR1 motif). It is located at -1918 to -1906 base pairs
      upstream of the transcription initiation site of this human ACOX gene. This PPRE
      specifically binds to baculovirus-expressed recombinant rat PPAR alpha/RXR alpha
      heterodimers. In transient transfection experiments, the maximum induction of
      luciferase expression by ciprofibrate and/or 9-cis-retinoic acid is dependent
      upon cotransfection of expression plasmids for PPAR alpha and RXR alpha. The
      functionally of this human ACOX promoter was further demonstrated by linking it
      to a beta-galactosidase reporter gene or to a rat urate oxidase cDNA and
      establishing stably transfected African green monkey kidney (CV1) cell lines
      expressing reporter protein. The human ACOX promoter has been found to be
      responsive to peroxisome proliferators in CV1 cells stably expressing PPAR alpha,
      whereas only a basal level of promoter activity is detected in stably transfected
      cells lacking PPAR alpha. The presence of a PPRE in the promoter of this human
      peroxisomal ACOX gene and its responsiveness to peroxisome proliferators suggests
      that factors other than the PPRE in the 5'-flanking sequence of the human ACOX
      gene may account for differences, if any, in the pleiotropic responses of humans
      to peroxisome proliferators.

PMID- 8567674
TI  - Mannose 6-phosphate receptors and ADP-ribosylation factors cooperate for high
      affinity interaction of the AP-1 Golgi assembly proteins with membranes.
AB  - Clathrin coat assembly in the trans-Golgi network, leading to the sequestration
      of the mannose 6-phosphate receptors (MPRs) into nascent vesicles, requires the
      ARF-1-dependent translocation of the cytosolic AP-1 Golgi assembly proteins onto
      the membranes of this organelle. The mechanistic role of the MPRs, i.e. the cargo
      molecules, in coat assembly is at present unclear. Using a GTP-dependent,
      brefeldin A-sensitive in vitro AP-1 binding assay, we have determined here the
      parameters of the AP-1 binding reaction. We demonstrate that, in addition of ARF
      1, the MPRs contribute to create high affinity AP-1 binding sites (Kd
      approximately 25 mM), since their number correlates the number of MPR molecules
      expressed in MPR-negative cells. The quantitative electron microscopy shows that
      these high affinity binding sites are present on trans-Golgi network membranes,
      as expected, and to some extent on early endosomes. The high affinity binding
      sites are lost when the MPRs or ARF-1 become rate-limiting components.
      Conversely, GTP gamma S (guanosine 5'-O-(3-thiotriphosphate)), which increases
      the amount of membrane-bound ARF-1, most uncovers low affinity AP-1 binding sites
      (Kd approximately 150 nM) on trans-Golgi network membranes, normally not detected
      in its absence. Collectively, these results argue that MPR sorting is highly
      coupled to the first step of coat assembly and that the MPRs, ARF-1, and possibly
      other proteins cooperate for high affinity interactions of AP-1.

PMID- 8567675
TI  - A casein kinase II phosphorylation site in the cytoplasmic domain of the cation
      dependent mannose 6-phosphate receptor determines the high affinity interaction
      of the AP-1 Golgi assembly proteins with membranes.
AB  - The transport of proteins from the secretory to the endocytic pathway is mediated
      by carrier vesicles coated with the AP-1 Golgi assembly proteins and clathrin.
      The mannose 6-phosphate receptors (MPHs) are two major transmembrane proteins
      segregated into these transport vesicles. Together with the GTPase ARF-1, these
      cargo proteins are essential components for the efficient translocation of the
      cytosolic AP-1 onto membranes of the trans-Golgi network, the first step of
      clathrin coat assembly, MPR-negative fibroblasts have a low capacity of
      recruiting AP-1 which can be restored by re-expressing the MPRs in these cells.
      This property was used to identify the protein motif of the cation-dependent
      mannose 6-phosphate receptor (CD-MPR) cytoplasmic domain that is essential for
      these interactions. Thus, the affinity of AP-1 for membranes and in vivo
      transport of cathepsin D were measured for MPR-negative cells re-expressing
      various CD-MPR mutants. The results indicate that the targeting of lysosomal
      enzymes requires the CD-PDR cytoplasmic domain that are different from tyrosine
      based endocytosis motifs. The first is a casein kinase II phosphorylation site
      (ESEER) that is essential for high affinity binding of AP-1 and therefore
      probably acts as a dominant determinant controlling CD-MPR sorting in the trans
      Golgi network. The second is the adjacent di-leucine motif (HLLPM), which, by
      itself, is not critical for AP-1 binding, but is absolutely required for a
      downstream sorting event.

PMID- 8567676
TI  - Involvement of arginine 120, glutamate 524, and tyrosine 355 in the binding of
      arachidonate and 2-phenylpropionic acid inhibitors to the cyclooxygenase active
      site of ovine prostaglandin endoperoxide H synthase-1.
AB  - Examination of the crystal structure of the ovine prostaglandin endoperoxide
      synthase-1 (PGHS-1)/S- flurbiprofen complex (Picot, D., Loll, P.J., and Garavito,
      R.M. (1994) Nature 367, 243-2491) suggests (a) that the carboxyl group of
      arachidonic acid interacts with the arginino group of Arg120; (b) that Arg120
      forms an important salt bridge with Glu524; and (c) that Tyr355, which is in
      close proximity to Arg120, could determine the stereochemical specificity of PGHS
      1 toward 2-phenylpropionic acid inhibitors. To test these concepts, we used site
      directed mutagenesis to prepare ovine PGHS-1 mutants having modifications of
      Arg120 (R120K, R120Q, R120E), Glu524 (E524D, E524Q, E524K), and Tyr355 (Y355F)
      and examined the properties of the mutant enzymes expressed in COS-1 cells. All
      of the mutants retained at least part of their cyclooxygenase and peroxidase
      activities except the R120E mutant, which had no detectable activity. The Km
      values of the R120K and R120Q mutants with arachidonic acid were 87 and 3300
      microM, respectively, versus 4 microM for native PGHS-1. The R120Q mutant failed
      to undergo suicide inactivation during catalysis or time-dependent inhibition by
      flurbiprofen. These results are consistent with Arg120 binding the carboxylate
      group of arachidonate and suggest that interaction of the carboxylate group of
      substrates and inhibitors with Arg120 is necessary for suicide inactivation and
      time-dependent inhibition, respectively. The Km values for the E524D, E524Q, and
      E524K mutants were not significantly different from values obtained for the
      native PGHS-1, suggesting that this residue is not importantly involved in
      catalysis or substrate binding. The effect of modifications of Arg120 and Tyr355
      on the stereospecificity of inhibitor binding was determined. Ratios of IC50
      values for cyclooxygenase inhibition by D- and L-ibuprofen, a competitive
      cyclooxygenase inhibitor, were 32, 67, and 7.1 for native PGHS-1, R120Q PGHS-1,
      and Y355F PGHS-1, respectively. The decreased stereochemical specificity observed
      with the Y355F PGHS-1 mutant suggests that Tyr355 is a determinant of the
      stereospecificity of PGHS-1 toward inhibitors of the 2-phenylpropionic acid
      class.

PMID- 8567677
TI  - Interactions of cyclophilin with the mitochondrial inner membrane and regulation
      of the permeability transition pore, and cyclosporin A-sensitive channel.
AB  - Mammalian mitochondria possess an inner membrane channel, the permeability
      transition pore (MTP), which can be inhibited by nanomolar concentrations of
      cyclosporin (CS) A. The molecular basis for MTP inhibition by CSA remains
      unclear. Mitochondria also possess a matrix cyclophilin (CyP) with a unique N
      terminal sequence (CyP-M). To test the hypothesis that it interacts with the MTP,
      we have studied the interactions of CyP-M with rat liver mitochondria by Western
      blotting with a specific antibody against its unique N terminus. Although
      sonication in isotonic sucrose at pH 7.4 refraction sediments with
      submitochondrial particles at 150,000 x g. We show that the interactions of this
      CyP-M pool with submitochondrial particles are disrupted (i) by the addition of
      CSA, which inhibits the pore, but not of CSH, which does not, and (ii) by acidic
      pH condition, which also leads to selective inhibition of the MTP; furthermore,
      we show that the effect of acidic pH on CyP-M fully prevents the inhibitory
      effect of H+ on the MTP (Nicolli, A., Petronilli, V., and Bernardi, P. (1993)
      Biochemistry 32, 4461-4465). These data suggest that CyP-M inhibition by CSA and
      protons may be due to unbinding of CyP-M from its putative binding site on the
      MTP. A role for CyP-M in MTP regulation is also supported by a study with a
      series of CSA derivatives with graded affinity for CyP. We show that with each
      derivative the isomerase activity of CyP-M purified to homogeneity is similar to
      that displayed at inhibition of MTP opening, CyP-M (but not CyP-A) and decreased
      efficiency at MTP inhibition is obtained by substitution in position 8 while a 4
      substituted, nonimmunosuppressive derivative is a as effective as the native CSA
      molecule, indicating that calcineurin is not involved in MTP inhibition by CSA.

PMID- 8567678
TI  - The V0 sector of the V-ATPase, synaptobrevin, and synaptophysin are associated on
      synaptic vesicles in a Triton X-100-resistant, freeze-thawing sensitive, complex.
AB  - Anti-synaptobrevin 2 immunoprecipitates obtained from freshly prepared Triton X
      100 extracts of rat synaptosomes contained, in addition to synaptophysin, a 10
      kDa band, which we identified by peptide sequencing and Western blotting as the c
      subunit of the vacuolar proton pump (V-ATPase) also called ductin or
      mediatophore. Ac39 and Ac116, two other transmembrane subunits of the V0 sector
      of the V-ATPase, were also found by Western blotting to be enriched in the
      immunoprecipitates. None of these V-ATPase subunits, or synaptophysin, was
      present in anti-synaptobrevin 2 immunoprecipitates obtained from frozen-thawed
      Triton X-100 extracts, which were greatly enriched, instead, in SNAP-25 and
      syntaxin 1. Accordingly, V-ATPase subunit c was found in anti-synaptophysin
      immunoprecipitates. Thus, the two complexes appear to be mutually exclusive.
      Subcellular fractionation of rat brain demonstrated that V-ATPase subunit c is
      localized with synaptobrevin 2 and synaptophysin in synaptic vesicles. The
      coprecipitation of V-ATPase subunit c with the synaptobrevin-synaptophysin
      complex suggests that this interaction may play a role in recruiting the proton
      pump into synaptic vesicles. Freeze-thawing, which involves a mild denaturing
      step, may produce a conformational change which dissociates the complex and
      mimics a change which occurs in vivo as a prerequisite to SNARE complex
      formation.

PMID- 8567679
TI  - The second intracellular loop of metabotropic glutamate receptor 1 cooperates
      with the other intracellular domains to control coupling to G-proteins.
AB  - Metabotropic glutamate receptors (mGluR) share no sequence homology with any
      other G-protein-coupled receptors (GPCRs). The characterization of their G
      protein coupling domains will therefore help define the general rules for
      receptor-G-protein interaction. To this end, the intracellular domains of mGluR3
      and mGluR1, receptors coupled negatively to adenylyl cyclase and positively to
      phospholipase C, respectively, were systematically exchanged. The ability of
      these chimeric receptors to induce Ca2+ signals were examined in Xenopus oocytes
      and HER 293 cells. The chimeric receptors that still possessed the second
      intracellular loop (i2) of these proteins were targeted correctly to the plasma
      membrane. Consistent Ca2+ signals could be recorded only with chimeric mGluR3
      receptors that contains i2 and at least one other intracellular domains of mGluR3
      have to be replaced by their mGluR1 equivalent to produce optimal coupling to G
      protein. These observations indicate that i2 of mGluR1 is a critical element in
      determining the transduction mechanism of this receptor. These results suggest
      that i2 of mGluRs may play a role similar to i3 of most other GPCRs in the
      specificity of coupling to the G-proteins. Moreover, as in many other GPCRs, our
      data revealed cooperation between the different mGluR intracellular domains to
      control efficient coupling to G-proteins.

PMID- 8567680
TI  - Molecular cloning of human fibroblast hyaluronic acid-binding protein confirms
      its identity with P-32, a protein co-purified with splicing factor SF2.
      Hyaluronic acid-binding protein as P-32 protein, co-purified with splicing factor
      SF2.
AB  - The purification of a 68-kDa hyaluronic acid-binding protein (HA-binding
      protein), a homodimer of 34 kDa that binds specifically to hyaluronic acid, has
      been reported earlier by us (Gupta, S., Batchu, R.B., and Datta, K. (1991) Eur.
      J. Cell Biol. 56, 58-67). Here, we report the isolation of a partial cDNA clone
      from a lambda gt11 cDNA expression library of human skin fibroblast by immuno
      screening with HA-binding protein antiserum. The internal polypeptide sequence
      (83 residues) of the purified hyaluronic acid-binding protein is identical to the
      predicted protein sequence derived from hyaluronic acid-binding protein cDNA,
      suggesting the authenticity of the clone. Interestingly, this hyaluronic acid
      binding protein cDNA sequence has complete homology with the cDNA sequence of a
      protein P-32, co-purified with the human pre-mRNA splicing factor SF2 (Krainer,
      A.R., Mayeda, A., Kozak, D., and Binns, G. (1991) Cell 66, 383-394). Furthermore,
      the data on the N-terminal sequence of hyaluronic acid-binding protein and the
      predicted polypeptide of P-32 revealed the identical coding sequence of 209 amino
      acids for both the proteins. As the identity and functional characterization of P
      32 have not yet been reported, P-32 cDNA was expressed in Escherichia coli, and
      the recombinant P-32 protein was purified by hyaluronic acid-Sepharose affinity
      chromatography. The recombinant P-32 protein showed immunocross-reactivity with
      the polyclonal antibodies raised against HA-binding protein. The predicted amino
      acid sequence of the protein fulfilled the minimal criteria for binding to
      hyaluronic acid, i.e. two basic amino acids flanking a seven-amino acid stretch,
      as reported for other hyaluronic acid affinity of the recombinant P-32 protein
      was confirmed by biotinylated hyaluronic acid binding assay. The binding of
      recombinant P-32 protein to biotinylated hyaluronic acid binding assay. The
      binding of recombinant P-32 protein to biotinylated hyaluronic acid can be
      competed only with excess unlabeled hyaluronic acid, confirming its specificity
      toward hyaluronic acid. All these results suggest that both P-32, co-purified
      with the human pre-mRNA splicing factor SF2, and 34-kDa hyaluronic acid-binding
      protein reported by us are the same protein and that it is a new member of the
      hyaluronic acid-binding protein family, the "hyaladherins."

PMID- 8567681
TI  - Kinetics and specificity of a H+/amino acid transporter from Arabidopsis
      thaliana.
AB  - The amino acid transporter AAP1/NAT2 recently cloned from Arabidopsis thaliana
      was expressed in Xenopus oocytes, and we used electrophysiological, radiotracer
      flux, and electron microscopic methods to characterize the biophysical
      properties, kinetics, and specificity of the transporter. Uptake of alanine was
      H(+)-dependent increasing from 14 pmol/oocyte/h at 0.032 microM H+ to 370
      pmol/oocyte/h at 10 microM H+. AAP1 was electrogenic; there was an amino acid
      induced depolarization of the oocyte plasma membrane and net inward currents
      through the transporter due to the transport of amino acids favoring neutral
      amino acids with shortside chains. The maximal current (imax) for alanine,
      proline, glutamine, histidine, and glutamate was voltage and [H+]o-dependent.
      Similarly, the imaxH was voltage and [amino acid]o-dependent. The imax for both
      H+ and amino acid were dependent on the concentrations of their respective
      cosubstrates, suggesting that both ligands bind randomly to the transporter. The
      K0.5 of the transporter for amino acids decreased as [H+]o increased and was
      lower at negative membrane potentials. The K0.5 for H+ was relatively voltage
      independent and decreased as [amino acid]o increased. This positive cooperativity
      suggests that the transporter operates via a simultaneous mechanism. The Hill
      coefficients n for amino acids and H+ were > 1, suggesting that the transporter
      has more than one binding site for both H+ and amino acid. Freeze-fracture
      electron microscopy was used to estimate the number of transporters expressed in
      the plasma membrane of oocytes. The density of particles on the protoplasmic face
      of the plasma membrane of oocytes expressing AAP1 increased approximately 5-fold
      above water-injected controls and corresponded to a turnover number 350 to 800 s
      1.

PMID- 8567682
TI  - Molecular cloning of a novel platelet protein showing homology to the angiotensin
      II receptor C-terminal domain.
AB  - Oligoscreening of a cDNA library obtained from 4 beta-phorbol 12-myristate 13
      acetate-stimulated human erythroleukemia (HEL) cells resulted in the isolation of
      a novel clone coding for a protein with a calculated molecular mass of 8110 Da.
      This protein of 71 amino acids shows significant homology to the carboxyl
      terminal regulatory domain of angiotensin II type 1 receptors. The homology
      encompasses four regions of amino acid residues thought to serve as consensus
      sequences for phosphorylation by serine/threonine kinases such as protein kinase
      C, which are key mediators of intracellular signaling. Reverse transcription
      polymerase chain reaction identified the transcript in human platelets, human
      megakaryocytic DAMI cells, and HEL cells. High stringency Northern blotting
      revealed a tissue-specific distribution of three transcript species, with
      predominant expression in skeletal muscle and pancreas. Rabbit anti-peptide
      antiserum was used to immunoblot protein lysates from washed resting platelets
      and from 4 beta-phorbol 12-myristate 13-acetate-stimulated DAMI and HEL cells.
      These immunoblots revealed the presence of an intense approximately 8-kDa protein
      band in platelets and HEL cells and a faint band of identical size in DAMI cells.

PMID- 8567683
TI  - The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide
      formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression,
      purification, kinetic analysis, and domain mapping.
AB  - We report here the cloning and sequencing of the cDNA, purification, steady state
      kinetic analysis, and truncation mapping studies of the human 5-aminoimidazole- 4
      carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase
      (AICARFT/IMPCHase). These steps of de novo purine biosynthesis, respectively. In
      all species of both prokaryotes and eukaryotes studied, these two activities are
      present on a single bifunctional polypeptide encoded on the purH gene. The human
      purH cDNA is 1776 base pairs in length encoding for a 591-amino acid polypeptic
      (Mr = 64,425). The human and avian purH cDNAs are 75 and 81% similar on the
      nucleotide and amino acid sequence level, respectively. The Km values for AICAR
      and (6R,6S)10-formyltetrahydrofolate are 16.8 microM +/- 1.5 and 60.2 microM +/-
      5.0, respectively, for the cloned, purified human enzyme. A 10-amino acid
      sequence within the COOH-terminal portion of human AICARFT/IMPCHase has some
      degree of homology to a previously noted "folate binding site." Site directed
      mutagenesis studies indicate that this sequence plays no role in enzymatic
      activity. We have constructed truncation mutants which demonstrate that each of
      the two enzyme activities can be expressed independent of the other. IMPCHase and
      AICARFT activities are located within the NH2-terminal 223 and COOH-terminal 406
      amino acids, respectively. The truncation mutant possessing AICARFT activity
      displays steady state kinetic parameters identical to those of the holoenzyme.

PMID- 8567684
TI  - Characterization of the functional domains on the C-terminal region of caldesmon
      using full-length and mutant caldesmon molecules.
AB  - A series of C-terminal deletion mutants of chicken gizzard smooth muscle
      caldesmon (CaD) were made using a polymerase chain reaction cloning strategy and
      a baculovirus expression system, and the precise locations of the functional
      domains of CaD involved in the regulation of actomyosin ATPase and the binding of
      actin, tropomyosin, and calmodulin were analyzed. Our results reveal a high
      affinity calmodulin-binding domain that consists of at least three calmodulin
      binding determinants localized in residues 690-717, 658-689, and 628-657. The
      residues between positions 718 and 756 and positions 598 and 627 have no
      detectable calmodulin-binding site. A high affinity tropomyosin-binding domain is
      located between residues 718 and 756. The 159 residues at the C terminus of CaD
      contain multiple actin-binding determinants; the major ones are localized in the
      regions between residues 718 and 756 and residues 690 and 717. The amino acid
      residues between positions 718 and 756 contain the major determinant involved in
      the inhibition of the actin activation of smooth muscle myosin ATPase since CaD
      (1-717) caused only 30% of the inhibition produced by the full-length CaD.
      Further deletion between residues 690 and 717 (CaD-(1-689) revealed a low level
      (10% of that seen for full-length CaD) of inhibition of the actomyosin ATPase.
      These data clearly demonstrate that the region of the last 66 amino acid residues
      at the CaD C terminus contains two or more major actin-binding motifs, one
      tropomyosin-binding domain, one high affinity calmodulin-binding determinant, and
      the domain that is responsible for the inhibition of the actin-activated ATPase
      of myosin.

PMID- 8567685
TI  - Neurite outgrowth in brain neurons induced by heparin-binding growth-associated
      molecule (HB-GAM) depends on the specific interaction of HB-GAM with heparan
      sulfate at the cell surface.
AB  - Heparin-binding growth-associated molecule (HB-GAM) is a cell-surface- and
      extracellular matrix-associated protein that lines developing axons in vivo and
      promotes neurite outgrowth in vitro. Because N-syndecan (syndecan-3) was found to
      function as a receptor in HB-GAM-induced neurite outgrowth, we have now studied
      whether the heparan sulfate side chains of N-syndecan play a role in HB-GAM
      neuron interactions. N-Syndecan from postnatal rat brain was found to inhibit HB
      GAM-induced but not laminin-induced neurite outgrowth when added to the assay
      media. The inhibitory activity was abolished by treating N-syndecan with
      heparitinase, but it was retained in N-syndecan-derived free glycosaminoglycan
      chains, suggesting that N-syndecan heparan sulfate at the cell surface is
      involved in HB-GAM-induced neurite outgrowth. Binding to HB-GAM and inhibition of
      neurite outgrowth was observed with heparin-related polysaccharides only;
      galactosaminoglycans were inactive. Significant inhibition of neurite outgrowth
      was induced by heparin and by N-syndecan heparan sulfate but not by heparan
      sulfates from other sources. A minimum of 10 monosaccharide residues were
      required for HB-GAM-induced neurite outgrowth. Experiments with selectively
      desulfated heparins indicated that 2-O-sulfated iduronic acid units, in
      particular, are of importance to the interaction with HB-GAM, were implicated to
      a lesser extent. Structural analysis of N-syndecan from 6-day-old rat brain
      indicated that the heparan sulfate chains contain sequences of contiguous, N
      sulfated disaccharide units with an unusually high proportion (82%) of 2-O
      sulfated iduronic acid residues. We suggest that this property of N-syndecan
      heparan sulfate is essential for HB-GAM binding and induction of neurite
      outgrowth.

PMID- 8567686
TI  - Mapping and functional role of phosphorylation sites in the thyroid transcription
      factor-1 (TTF-1).
AB  - The phosphorylation of thyroid transcription factor-1 (TTF-1), is homeodomain
      containing transcription factor that is required for thyroid-specific expression
      of the thyroglobulin and thyroperoxidase gene promoters, has been studied.
      Phosphorylation occurs on a maximum of seven serine residues that are distributed
      in three tryptic peptides. Mutant derivatives of TTF-1, with alanine sites, have
      been constructed and used to assess the functional relevance of TTF-1
      phosphorylation. The DNA binding activity of TTF-1 appears to be phosphorylation
      independent, as indicated also by the performance of TTF-1 purified from an
      overexpressing Escherichia coli strain. Transcriptional activation by TTF-1 could
      require phosphorylation only in specific cell types since in a co-transfection
      assay in heterologous cells both wild-type and mutant proteins show a similar
      transcriptional activity.

PMID- 8567687
TI  - Molecular cloning of caveolin-3, a novel member of the caveolin gene family
      expressed predominantly in muscle.
AB  - Caveolin, a 21-24-kDa integral membrane protein, is a principal component of
      caveolar membranes in vivo. Caveolin interacts directly with heterotrimeric G
      proteins and can functionally regulate their activity. Recently, a second
      caveolin gene has been identified and termed caveolin-2. Here, we report the
      molecular cloning and expression of a third member of the caveolin gene gamily,
      caveolin-3. Caveolin-3 is most closely related to caveolin-1 based on protein
      sequence homology; caveolin-1 and caveolin-3 are approximately 65% identical and
      approximately 85% similar. A single stretch of eight amino acids (FED-VIAEP) is
      identical in caveolin-1, -2, and -3. This conserved region may represent a
      "caveolin signature sequence" that is characteristic of members of the caveolin
      gene family. Caveolin-3 mRNA is expressed predominantly in muscle tissue-types
      (skeletal muscle, diaphragm, and heart) and is selectively induced during the
      differentiation of skeletal C2C12 myoblasts in culture. In many respects,
      caveolin-3 is similar to caveolin-1: (i) caveolin-3 migrates in velocity
      gradients as a high molecular mass complex; (ii) caveolin-3 colocalizes with
      caveolin-1 by immunofluorescence microscopy and cell fractionation studies; and
      (iii) a caveolin-3-derived polypeptide functionally suppresses the basal GTPase
      activity of purified heterotrimeric G-proteins. Identification of a muscle
      specific member of the caveolin gene family may have implications for
      understanding the role of caveolin in different muscle cell types (smooth,
      cardiac, and skeletal) as previous morphological studies have demonstrated that
      caveolae are abundant in these cells. Our results also suggest that other as yet
      unknown caveolin family members are likely to exist and may be expressed in a
      regulated or tissue-specific fashion.

PMID- 8567688
TI  - Selected novel flavones inhibit the DNA binding or the DNA religation step of
      eukaryotic topoisomerase I.
AB  - Topoisomerases are involved in many aspects of DNA metabolism such as replication
      and transcription reactions. Camptothecins, which stabilize the covalent
      intermediate of topoisomerase I and DNA are effective, though toxic, drugs for
      cancer therapy. In this study, a new class of topoisomerase I inhibitors was
      identified, and their mode of action was characterized using recombinant human
      topoisomerase I preparations and human HL-60 leukemic cells. Quercetin and the
      related natural flavones, acacetin, apigenin, kaempferol, and morin, inhibit
      topoisomerase I-catalyzed DNA religation. In contrast to camptothecin, these
      compounds do not act directly on the catalytic intermediate and also do not
      interfere with DNA cleavage. However, formation of a ternary complex with
      topoisomerase I and DNA during the cleavage reaction inhibits the following DNA
      religation step. 3,3',4',7-Tetrahydroxy-substituted flavones stabilize the
      covalent topoisomerase I-DNA intermediate most efficiently. Enhanced formation of
      covalent topoisomerase I-DNA complexes was also demonstrated in human HL-60
      cells. In contrast, synthetic 3,5'-dibromo- 4'-hydroxy-3-methylflavones bind
      selectively to topoisomerase I in its non-DNA-bound form and block the following
      DNA binding step. As a consequence, these synthetic flavonoids are capable of
      counteracting topoisomerase I-directed effects of camptothecin. Inhibition of DNA
      binding is obtained by voluminous hydrophobic substituents in 6-position of the
      flavone structure. Our data show that selective inhibitors of both half-reactions
      of topoisomerase I can be derived from the flavone structure.

PMID- 8567689
TI  - A novel meprin beta' mRNA in mouse embryonal and human colon carcinoma cells.
AB  - Meprins, metalloendopeptidases of the astacin family, are composed of alpha
      and/or beta subunits and are expressed at high levels in mammalian renal and
      intestinal brushborder membranes. Only one mRNA has been identified previously
      for each of the subunits in adult human and rodent tissues; a 3.6-kilobase
      message for the alpha subunit and a 2.5-kilobase message for the beta subunit.
      The present study reports that a larger beta subunit message (2.7 kilobases,
      referred to as beta'), and no alpha subunit message, is expressed in embryonal
      carcinoma cell lines, F9 and Nulli-SSC1, and in human colon adenocarcinoma cells,
      HT-28-18-C1. Furthermore, in Nulli-SSC1 cells, the beta isoform is induced by the
      morphogen retinoic acid. The beta' isoform differs from beta only in a portion of
      the 5'-coding (corresponding to the signal and prosequence domains of the
      protein) and noncoding region. Only one gene was found for the beta subunit in
      the mouse and human genome. The deduced amino acid sequence of beta' has no
      homology with beta in the first 35 NH2-terminal residues, but the two sequences
      are identical after that. In vitro translation experiments indicated that the
      size of the protein product of beta' cDNA was similar to that of the beta cDNA
      protein product, and, in the presence of microsomal membranes, both were
      glycosylated. These studies indicate that the messages for the meprin beta and
      beta' subunit result from differential promoter usage and alternate splicing.
      Expression of the two isoforms may be regulated differentially depending on cell
      type and/or differentiation state of the cell.

PMID- 8567690
TI  - Cytoplasmic domain of rhodopsin is essential for post-Golgi vesicle formation in
      a retinal cell-free system.
AB  - In retinal photoreceptors, highly polarized organization of the light-sensitive
      organelle, the rod outer segment, is maintained by the sorting of rhodopsin and
      its associated proteins into distinct post-Golgi vesicles that bud from the trans
      Golgi network (TGN) and by their vectorial transport toward the rod outer
      segment. We have developed an assay that reconstitutes the formation of these
      vesicles in a retinal cell-free system. Vesicle formation in this cell-free assay
      is ATP-, GTP-, and cytosol-dependent. In frog retinas vesicle budding also
      proceeds at 0 degrees C, both in vivo and in vitro. Vesicles formed in vitro are
      indistinguishable from the vesicles formed in vivo by their buoyant density,
      protein composition, topology, and morphology. In addition to the previously
      identified G-proteins, these vesicles also contain rab11. Concurrently with
      vesicle budding, resident proteins are retained in the TGN. Collectively these
      data suggest that rhodopsin and its associated proteins are sorted upon exit from
      the TGN in this cell-free system. Removal of membrane-bound GTP-binding proteins
      of the rab family by rab GDP dissociation inhibitor completely abolishes
      formation of these vesicles and results in the retention of rhodopsin in the
      Golgi. A monoclonal antibody to the cytoplasmic (carboxy-terminal) domain of
      rhodopsin and its Fab fragments strongly inhibit vesicle formation and arrest
      newly synthesized rhodopsin in the TGN rather than the Golgi. Therefore rhodopsin
      sorting at the exit from the TGN is mediated by the interaction of its
      cytoplasmic domain with the intracellular sorting machinery.

PMID- 8567691
TI  - Purification and characterization of UDP-glucose:ceramide glucosyltransferase
      from rat liver Golgi membranes.
AB  - We present a method for solubilizing and purifying UDP-Glc:ceramide
      glucosyltransferase (EC 2.4.1.80; glucosylceramide synthase (GCS) from a rat
      liver and present data on its substrate specificity. A Golgi membrane fraction
      was isolated, washed with N-lauroylsarcosine, and subsequently treated with 3[3
      cholamidopropyl)-dimethylammonio]-2-hydroxy-1-propanesulfonate to solubilize the
      enzyme. GCS activity was monitored throughout purification using UDP-Glc and a
      fluorescent ceramide analog as substrates. Purification of GCS was achieved via a
      two-step dye-agarose chromatography procedure using UDP-Glc to elute the enzyme.
      This resulted in an enrichment > 10,000-fold relative to the starting homogenate.
      The enzyme was further characterized by sedimentation on a glycerol gradient, I
      labeling, and SDS-polyacrylamide gel electrophoresis. which demonstrated that two
      polypeptides (60-70 kDa) corresponded closely with GCS activity. Purified GCS was
      found to require exogenous phospholipids for activity, and optimal results were
      obtained using dioleoyl phosphatidylcholine. Studies of the substrate specificity
      of the purified enzyme demonstrated that it was stereospecific and dependent on
      the nature and chain length of the N-acyl-spingosine or -sphinganine substrate.
      UDP-Glc was the preferred hexose donor, but TDP-glucose and CDP-glucose were also
      efficiently used. This study provides a basis for molecular characterization of
      this key enzyme in glycosphingolipid biosynthesis.

PMID- 8567692
TI  - Pancreatic islet expression of the homeobox factor STF-1 relies on an E-box motif
      that binds USF.
AB  - The commitment of cells to specific lineages during development is determined in
      large part by the relative expression of various homeodomain (HOX) selector
      proteins, which mediate the activation of distinct genetic programs. But the
      mechanisms by which individual HOX genes are themselves targeted for expression
      in different cell types remain largely uncharacterized. Here, we demonstrate that
      STF-1, a homeodomain protein that functions in pancreatic morphogenesis and in
      glucose homeostasis is encoded by an "orphan" homeobox gene on mouse chromosome
      5. When fused to a beta-galactosidase reporter gene, a 6.5-kilobase genomic
      fragment of 5'-flanking sequence from the STF-1 gene shows pancreatic islet
      specific activity in transgenic mice. Two distinct elements within the STF-1
      promoter are required for islet-restricted expression: a distal enhancer sequence
      located between -3 and -6.5 kilobases and a proximal E-box sequence located at 
      104, which is recognized primarily by the helix loop helix/leucine zipper nuclear
      factor USF. As point mutation within the -104 E-box that disrupt USF binding
      correspondingly impair STF-1 promoter activity, our results demonstrate that USF
      is an important component of the regulatory apparatus which directs STF-1
      expression to pancreatic islet cells.

PMID- 8567693
TI  - Modulation of iron regulatory protein functions. Further insights into the role
      of nitrogen- and oxygen-derived reactive species.
AB  - Iron regulatory protein (IRP) is a cytosolic bifunctional [Fe-S] protein which
      exhibits aconitase activity or binds iron responsive elements (IREs) in
      untranslated regions of specific mRNA. The modulators of these activities are the
      intracellular concentration of iron and, as recently described, NO synthase
      activity. In this study, we attempted to establish in in vitro experiments
      whether peroxynitrite (ONOO-, the product of the reaction between NO and O2-.),
      as well as oxygen-derived radicals (O2-. and H2O2) and various NO donors, allow
      IRP to bind IREs using cytosol extract of macrophagelike RAW 264.7 cells. Neither
      the addition of a bolus of ONOO- or H2O2 nor O2-. generation significantly
      affected IRE binding even though they inhibited its aconitase activity. Moreover,
      we show that 3-morpholinosydnonimine (SIN-1), a chemical which releases both NO
      and O2-. enhanced IRE binding activity of IRP only in the presence of superoxide
      dismutase (SOD). S-Nitrosothiols and the NONOate sper/NO plus gluthathione (GSH)
      activated IRE binding by IRP whereas oxyhemoglobin prevented enhancement of this
      binding by SIN-1/SOD and sper/NO plus GSH. cis-Aconitate, substrate, also
      abolished the effect of SIN-1/SOD on IRE binding by IRP. These results imply that
      neither O2-. nor ONOO- can convert [4Fe-4S] IRP into IRE-binding protein but
      rather suggest that an active redox form of NO converts IRP into its IRE binding
      form by targeting the [Fe-S] cluster.

PMID- 8567694
TI  - Identification of an inverted CCAAT box motif in the fatty-acid synthase gene as
      an essential element for modification of transcriptional regulation by cAMP.
AB  - The antagonistic effect of cAMP on the insulin-induced expression of fatty acid
      synthase (FAS) in liver could be mimicked in vitro using H4IIE hepatoma cells,
      both by measuring the response of the endogenous FAS gene and by assaying
      expression of transfected reporter genes containing promoter elements of the FAS
      gene. 5'-Deletion analysis and replacement mutagenesis revealed that an essential
      element required for cAMP antagonism of the insulin effect is an inverted CCAAT
      box located between nucleotides -99 and -92. DNase I foot-printing and gel shift
      analysis revealed that this region can bind a protein present in nuclei of liver
      and spleen, organs that express high and undetectable levels of FAS,
      respectively. This protein is not a CCAAT/enhancerbinding protein, C/EBP. Thus,
      the FAS gene appears unusual in that the sequence element required for
      transcriptional regulation by cAMP is neither a cAMP response element (CRE) nor a
      binding site for AP-1, AP-2, or C/EBP. These results suggest that essential to
      the regulation of FAS transcription by cAMP is the interaction of an inverted
      CCAAT box motif with a constitutively produced trans-acting factor that either
      itself undergoes modification in response to cAMP or associated with a protein
      that is produced or modified by cAMP exposure.

PMID- 8567695
TI  - Mechanism of inhibition of vaccinia DNA topoisomerase by novobiocin and
      coumermycin.
AB  - Vaccinia DNA topoisomerase, a eukaryotic type I enzyme, has unique
      pharmacological properties, including sensitivity to the coumarin drugs
      novobiocin and coumermycin, which are classical inhibitors of DNA gyrase, a type
      II enzyme. Whereas coumarins inhibit gyrase by binding the GyrB subunit and
      thereby blocking the ATP-binding site, they inhibit vaccinia topoisomerase by
      binding to the protein and blocking the interaction of enzyme with DNA.
      Noncovalent DNA binding and single-turnover DNA cleavage by topoisomerase are
      inhibited with K1 values of 10-25 microM for coumermycin and 350 microM for
      novobiocin. Spectroscopic and fluorescence measurements of drug binding t enzyme
      indicate a single binding site on vaccinia topoisomerase for coumermycin (KD = 27
      +/- 5 microM) and two classes of binding sites for novobiocin, one tight site
      (KD1 = 20 +/- 5 microM) and several weak sites (KD2 = 513 +/- 125 microM; n = 4.9
      +/- 0.7). Addition of a stoichiometric amount of DNA to a performed coumermycin
      topoisomerase complex quantitatively displaces the drug, indicating that
      coumermycin binding and DNA binding to topoisomerase are mutually exclusive. A
      simple interpretation is that the site of drug binding coincides or overlaps with
      the DNA-binding site on the topoisomerase. Both novobiocin and coumermycin alter
      the susceptibility of vaccinia topoisomerase to proteolysis with either
      chymotrypsin or trypsin; similar effects occur when topoisomerase binds to duplex
      DNA.

PMID- 8567696
TI  - Liver-enriched transcription factor HNF-4 and ubiquitous factor NF-Y are critical
      for expression of blood coagulation factor X.
AB  - Blood coagulation Factor X and its activated form Factor Xa play an essential
      role in the midphase of the clotting cascade. To delineate the mechanisms
      governing the liver-specific expression of Factor X, we have previously
      characterized the complete 2.8 kilobase pairs of the 5'-flanking region of Factor
      X and demonstrated that the first 209 base pairs is sufficient to confer maximal
      promoter activity in HepG2 cells, a hepatoma cell line that expresses Factor X.
      We have also shown that mutations at ACTTTG and CCAAT elements located at -56 to 
      51 and -120 to -116, respectively, significantly reduce the promoter activity. In
      this report, we demonstrate that Factor X mRNA is primarily but not exclusively
      expressed in the liver. Using DNase I footprinting analysis, we determine four
      protein binding sites within the 209-base pair fragment, designated site 1 (-73)
      to -44), site 2 (-128 to -94), site 3 (-165 to -132), and site 4(-195 to -169).
      Using gel mobility shift assays in combination with competition and supershift
      experiments, we demonstrate that hepatocyte nuclear factor 4 and Sp1 bind at site
      1, the site which contains the ACTTTG element. Methylation interference assays
      reveal that HNF-4 and Sp1 contact adjacent sites with minor overlap. HNF-4 and
      Sp1 appear to bind site 1 in a mutually exclusive fashion. We also demonstrate
      that HNF-4 can transactivate the Factor X promoter in HeLa cells; mutation at the
      adjacent Sp1 site further increases the transactivation. Heteromeric
      transcription factor NF-Y was identified as the protein that binds the CCAAT box
      at site 2. We conclude that HNF-4 and NF-Y play crucial roles in modulating the
      activity of the proximal promoter of Factor X.

PMID- 8567697
TI  - The epithelial mucin MUC1 contains at least two discrete signals specifying
      membrane localization in cells.
AB  - The MUC1 gene product (PEM, polymorphic epithelial mucin) is a cell-associated
      glycoprotein expressed on the apical surface of most simple secretory epithelia.
      The transmembrane and cytoplasmic domains of MUC1 have been shown to be highly
      conserved between mammalian species, and it has been shown that this molecule
      interacts with the actin cytoskeleton. Apical targeting signals in polarized
      cells have yet to be defined. The mechanism by which MUC1 is targeted and
      maintained on the apical surface is not known; correct localization, however,
      would be predicted to be crucial for function. In order to determine which
      domains of MUC1 were important for this localization, mutational analysis of the
      protein was undertaken. Using cytoplasmic tail deletion mutants, fusion proteins
      of MUC1 and CD2, and site-directed mutagenesis, it could be shown that MUC1
      appeared to contain at least two motifs involved in apical localization. The
      first was located in the extracellular domain and was sufficient to confer apical
      localization on the fusion protein. The second was the Cys-GlnCys (CQC) motif at
      the junction of the cytoplasmic and transmembrane domains. This sequence was
      necessary for surface expression. These results suggest that MUC1 contains two
      discrete motifs important in its apical localization.

PMID- 8567698
TI  - Microtubular disruption prolongs the expression of human bilirubin
      uridinediphosphoglucuronate-glucuronosyltransferase-1 gene transferred into Gunn
      rat livers.
AB  - DNA delivered to the liver by asialoglycoprotein receptor-mediated endocytosis is
      degraded in lysosomes within 48 h. To test the hypothesis that microtubular
      disruption should promote transgene persistence by interrupting endosomal
      translocation to lysosomes, plasmids containing bacterial chloramphenicol
      acetyltransferase (pSV2-CAT) or human bilirubin-UDP-glucuronosyltransferase-1
      (pSVK3-hBUGT1) genes were complexed with asialoglycoprotein-polylysine
      conjugates, and 1 mg of the complexed DNA was injected intravenously into
      bilirubin-UDP-glucuronosyltransferase-deficient Gunn rats. 30 min before DNA
      injection, one group received 0.75 mg of colchicine/kg of body weight
      intraperitoneally, which was shown by immunofluorescent confocal microscopy to
      disrupt the microtubular network. Control rats received normal saline. In
      colchicine-pretreated rats receiving pSV2-CAT, hepatic chloramphenicol
      acetyltransferase activity persisted for 9-14 weeks, whereas in the saline
      pretreated group the activity was detectable for 48 h only. In colchicine
      pretreated Gunn rats receiving pSVK3-hBUGT1, the DNA persisted in liver for 10
      weeks, bilirubin glucuronides were excreted in bile, and serum bilirubin levels
      declined by 25-35% in 2-4 weeks and remained reduced for 8 weeks. Without
      colchicine pretreatment, the DNA was detectable in liver for 2 days only, and
      serum bilirubin levels were not reduced. Thus, microtubular disruption provides a
      noninvasive method for prolonging the effect of liver-targeted gene therapy.

PMID- 8567699
TI  - Functional and molecular mitochondrial abnormalities associated with a C --> T
      transition at position 3256 of the human mitochondrial genome. The effects of a
      pathogenic mitochondrial tRNA point mutation in organelle translation and RNA
      processing.
AB  - We have previously identified a mitochondrial DNA polymorphism (a C --> T
      transition at position 3256, within the mitochondrial tRNALeu(UUR) gene in a
      patient with a multisystem disorder. Although there were several indicators
      suggesting a pathogenetic role for this mtDNA polymorphism, its heteroplasmic
      nature made functional and molecular studies difficult to interpret. We have now
      fused enucleated fibroblasts from the patient with a mtDNA-less cell line to
      generate transmitochondrial cybrids harboring different proportions of mutated
      and wild-type mtDNA. Individual clones harboring essentially 100% wild-type or >
      99% mutated mtDNAs were characterized and studied for respiratory capacity,
      respiratory chain enzymes activity, mitochondrial protein synthesis, and RNA
      steady-state levels and processing. Our results showed that cell lines containing
      exclusively mutated mtDNAs respire poorly, overproduce lactic acid, and have
      significantly impaired activity of respiratory complexes I and IV. Molecular
      studies showed that mutant clones have a decrease in steady-state levels of
      mitochondrial tRNALeu(UUR), and a partial impairment of mitochondrial protein
      synthesis and steady-state levels, suggesting that these molecular abnormalities
      are involved in the pathogenetic mechanism of the mtDNA 3256 mutation.

PMID- 8567700
TI  - The current status of regulatory affairs in the orthopedic industry.

PMID- 8567702
TI  - Photochemical surface derivatization of a peptide containing Arg-Gly-Asp (RGD).
AB  - A photoreactive octapeptide (Gly-Gly-Gly-Arg-Gly-Asp-Ser-Pro), into which the
      cell adhesive tripeptidyl sequence Arg-Gly-Asp (RGD) was incorporated, was
      derivatized with 4-azidobenzoyloxysuccinimide at its N-terminal. Photochemical
      surface immobilization of the RGD peptide on poly (vinyl alcohol) (PVA) was
      performed by adsorption and subsequent ultraviolet (UV) irradiation and was
      evidenced by electron spectra for chemical analysis (ESCA) measurements. Bovine
      endothelial cells (ECs) adhered and spread well on the RGD peptide-derivatized
      surfaces in a biologically specific manner. The use of a photomask during UV
      irradiation enabled preparation of a two-dimensional tissue with micron-order
      precision. Thus surface immobilization of a photoreactive, cell-adhesive peptide
      easily can create a cell attachment surface at a desired portion or region of a
      polymer surface or device.

PMID- 8567701
TI  - Assessments of thrombogenicity by three in vitro techniques. Student Research
      Award in the Undergraduate, Master Candidate, or Health Science Degree Candidate
      Category, 21st annual meeting of the Society for Biomaterials, San Francisco, CA,
      March 18-22, 1995.
AB  - This study assessed three in vitro techniques designed to measure the
      thrombogenicity of vascular grafts. All techniques immersed vascular grafts in
      rotating blood. In the gravimetric analysis, the weight of adherent thrombi was
      recorded at 2 min intervals for 20 min. In the torque analysis, a microviscometer
      continuously recorded the amount of torque developed as the graft rotated for 20
      min. In the thrombin analysis, the blood sample was analyzed for fibrinopeptide A
      production indicating fibrinogen cleavage. Expanded polytetrafluoroethylene
      grafts were treated by removal of air nuclei (denucleation), binding of heparin,
      or binding of polyethylene oxide (PEO). The gravimetric analysis determined that
      the time at which each group experienced clot initiation was as follows: control
      after 6 min, denucleation after 14 min, heparin after 18 min, and PEO after 10
      min. Similarly, in the torque analysis all treatment groups significantly delayed
      the initial increase in torque from 8.0 min for control to 12.5 min for
      denucleation (P < .01), > 20 min for heparin (P < .01), and 12 min for PEO (p <
      .05). The thrombin analysis determined that coagulation activity was reduced
      relative to control at 12 min with the denucleation group (P < .05) and heparin
      group (P < .01) and at 18 min with all treatment groups (P < .01). The similarity
      of results among the techniques increases confidence that each measurement
      accurately predicts in vitro thrombogenicity.

PMID- 8567703
TI  - Comparison of the release of growth hormone from hydroxyapatite, heat-treated
      hydroxyapatite, and fluoroapatite coatings on titanium.
AB  - Hydroxyapatite (HA), heat-treated hydroxyapatite (HAH), and fluorapatite (FA)
      coatings on titanium were loaded with human growth hormone (GH), and the
      subsequent release was monitored in vitro. The amount of GH released was
      significantly increased from the HA coating that had received a post-plasma
      spraying heat treatment prior to incorporation of the growth hormone. Scanning
      electron microscopy was used to assess the surfaces of the ceramic coatings prior
      and postincubation with GH. Surface changes were observed on the HA and HAH
      coatings but not on the FA coatings after incubation with GH. Osteoblast-like
      cells were grown on the coatings and maintained in culture. Scanning electron
      microscopy was used to study the morphology of the cells and the interaction of
      the cells with the ceramic coatings. We used thymidine uptake and DNA content to
      determine the relative rates of cell division on the different coatings; the
      optimum rate of cell proliferation was observed on the HAH coating loaded with
      0.1 IU/mL GH.

PMID- 8567704
TI  - Effect of calcium phosphate (Ca-P) coatings on trabecular bone response: a
      histological study.
AB  - The trabecular bone response to noncoated and fluorapatite (FA), hydroxyapatite
      (HA), and hydroxyapatite heat-treated (HAHT) plasma-sprayed coated implants was
      investigated in a goat animal model. Forty-eight cylindrical implants were
      inserted into the trabecular bone of the lateral and medial femoral condyles of
      twelve goats according to a split plot design. After an implantation period of
      twelve weeks, the bone-implant interface was evaluated histologically.
      Quantitative histomorphometrical measurements demonstrated a significant
      difference in bone contact between implants inserted in the lateral and medial
      condyles. In addition, a significant difference in bone apposition was observed
      between the coated and the uncoated implants. Finally, all Ca-P coatings showed
      reduction in coating thickness. Measurements revealed that FA and HAHT showed
      less reduction in coating thickness than HA coating. Despite the coating
      reduction, the bone remained in close contact with the implant surface.

PMID- 8567705
TI  - Characterization of thin hydroxyapatite layers formed on anodic titanium oxide
      films containing Ca and P by hydrothermal treatment.
AB  - An anodic titanium oxide film containing Ca and P (AOFCP) was formed on
      commercially pure titanium which was anodized in an electrolytic solution of
      dissolved beta-glycerophosphate (beta-GP) and calcium acetate (CA).
      Hydroxyapatite (HA) crystals were precipitated by hydrothermally heating the
      AOFCP at 300 degrees C. After hydrothermal treatment, the film was characterized
      by scanning electron microscopy (SEM), energy-dispersive X-ray microanalysis
      (EDX), and tensile tests. The morphology, composition, and amount of HA crystals
      precipitated were significantly affected by the composition of the electrolytes.
      Near-stoichiometric HA crystals with high crystallinity were precipitated
      completely covering the AOFCP surface at specific electrolyte concentrations. The
      HA layers were thin at 1-2 microns in thickness. The adhesive strength of the
      film increased with decreasing electrolyte concentration and the maximum value
      was about 40 MPa. In vitro tests for 300 days suggested that the stability of the
      film was high. The high adhesive strength may result from the AOFCP existing as
      an intermediate layer between the HA layer and a titanium substrate. The
      intervention of the AOFCP may have prevented abrupt changes in Ca and P content
      at an HA coating-titanium interface as seen in a plasma-sprayed one. The porous
      TiO2 matrix of the AOFCP may be suitable for nucleation sites of HA crystals, as
      well as SiO2 matrix of silicate bioactive glasses or glass ceramics.

PMID- 8567706
TI  - Bone-bonding behavior under load-bearing conditions of an alumina ceramic implant
      incorporating beads coated with glass-ceramic containing apatite and
      wollastonite.
AB  - Alumina ceramic with a porous surface coated with glass-ceramic containing
      apatite and wollastonite (AW-GC) was implanted in a state of press-fit under load
      bearing conditions in the femoral condylus of the mongrel dog and compared with a
      non-glass-ceramic-coated alumina ceramic. A trapezoid alumina ceramic implant (7
      x 10 x 5 mm) with a lateral recess (0.9 mm deep) coated with alumina ceramic
      beads (mean diameter, 750 microns) in a single layer was prepared. The alumina
      ceramic beads were bonded to the alumina ceramic substratum using an identical
      alumina binder. The thickness of coating was 10-50 microns (mean, 30 microns).
      The surface of the beads and the substratum of the alumina implant were coated
      with AW-GC. A pull-out test and histologic examination were performed at 4, 8,
      and 24 weeks after implantation. The interfacial shear load was significantly
      increased from 8 to 24 weeks in both groups. The shear load of the glass-ceramic
      coated implant was significantly greater than that of the noncoated implant at
      every stage. The interface shear load of the noncoated implant was 12.13 +/- 2.76
      kg at 4 weeks, 13.92 +/- 4.18 kg at 8 weeks, and 24.17 +/- 5.17 kg at 24 weeks
      after implantation. The interface shear load of the glass-ceramic-coated implant
      was 17.96 +/- 2.81 kg at 4 weeks, 24.92 +/- 9.87 kg at 8 weeks, and 34.83 +/-
      4.12 kg at 24 weeks after implantation. Histologic examination showed more
      ingrown bone tissue in the glass-ceramic-coated implants. It is suggested that AW
      GC stimulated the bone ingrowth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567707
TI  - Cellular responses to chemical and morphologic aspects of biomaterial surfaces.
      I. A novel in vitro model system.
AB  - The clinical success of any implant is directly dependent upon the cellular
      behavior in the immediate vicinity of the interface established between the host
      tissue and the biomaterial(s) used to fabricate the device. All biomaterials have
      morphologic, chemical, and electrical surface characteristics that influence the
      cellular response to the implant. Quantitative measurement of specific aspects of
      this local host response to different but well-characterized biomaterial surfaces
      provides a crucial link in the understanding of the overall phenomenon of implant
      biocompatibility. A system has been devised for in vitro examination of responses
      of cells to controlled but independent changes in both the chemistry and
      morphology of polystyrene (PS) tissue culture surfaces. Micromachined silicon
      wafers were used as templates to solvent-cast PS replicas [using 0, 1, or 2 wt %
      styrene (S) monomer additions] with either none, 0.5- or 5.0-microns-deep surface
      grooves arranged in a radial array. When all possible morphologies were combined
      with all possible polymers, nine model biomaterial surfaces (MBSs) were produced.
      The chemical characteristics of the MBSs were determined using electron
      spectroscopy for chemical analysis, secondary ion mass spectroscopy, and contact
      angle techniques and were found to be distinct. The types and amount of proteins
      that adsorb onto these surfaces from serum containing media were examined and
      found to consist of multiple molecular layers of relatively uniform composition.
      Self-contained tissue culture vessels formed from the MBSs were capable of
      supporting the growth of confluent cultures of rat calvarial cells. The model
      biomaterial system described here can be used to examine how simultaneous stimuli
      resulting from the chemical and morphological characteristics of a test material
      may influence biologic responses. Such multifactorial biocompatibility research
      is needed to properly document material-host interactions.

PMID- 8567709
TI  - Field emission SEM comparison of four postfixation drying techniques for human
      dentin.
AB  - Critical-point drying (CPD) is generally considered essential for the preparation
      of biologic specimens for electron microscopy. Several attempts have been made to
      introduce alternative techniques. More recently, this problem has arisen in
      dentistry, because of the new developments in dentin bonding. The present study
      focuses on three alternative techniques to CPD: hexamethyldisilazane (HMDS)
      drying, Peldri II drying, and air drying. Twenty-four dentin disks were obtained
      from noncarious extracted human molars by microtome sectioning parallel to the
      occlusal surface. The dentin surfaces were etched with polymer-thickened, silica
      free, 10% phosphoric acid semigel, fixed, dehydrated, and dried with one of the
      four techniques. The specimens were observed in two perpendicular planes, showing
      dentinal tubules in longitudinal view and cross-section, using a field emission
      scanning electron microscope. The intertubular demineralized dentin zone was
      composed of three different successive layers, which did not substantially differ
      between CPD and Peldri II drying, but were more evident in HMDS-dried specimens:
      first, an upper layer of denatured collagen and residual smear layer particles,
      with sectioned collagen fibrils and few open intertubular pores; second, an
      intermediate layer of closely packed cross-sectioned collagen fibers; and third,
      a deeper layer with unfilled spaces, scattered hydroxyapatite crystals, and few
      collagen fibers. HMDS drying seemed to preserve better the collagen network and
      the microporosity of the demineralized dentin surface. Moreover, HMDS drying is
      easy to perform. The air-drying method caused some artefacts, such as surface
      collapsing and thickening of the denatured collagen layer.

PMID- 8567708
TI  - Cellular responses to chemical and morphologic aspects of biomaterial surfaces.
      II. The biosynthetic and migratory response of bone cell populations.
AB  - The biosynthetic and migratory response of bone cells to changes in both surface
      composition and morphology of polystyrene (PS) substrates was examined. A system
      was devised wherein micromachined silicon wafers were used as templates to
      solvent-cast PS replicas [using 0, 1, or 2 wt % styrene (S) monomer additions]
      with either 0.5- or 5.0- microns-deep surface grooves. Smooth replicas (0% S)
      served as the control surfaces. The chemical and morphologic characteristics of
      the nine unique model biomaterial surfaces (MBSs) produced using this system were
      documented and were found to be distinct. For the biosynthetic studies, bone
      cells isolated from neonatal rat calvaria were plated onto the MBSs and labeled
      at postconfluence with [14C]proline for 24 h. Total DNA per surface, total newly
      synthesized collagenous (CP), and noncollagenous protein (NCP) (cell associated
      and secreted) were determined. Cell-associated CP was found to increase
      significantly for the bone cells cultured on the substrates with 0.5-micron
      grooves and 2% S (P < .05). Cell-associated NCP was found to be elevated for all
      2% S substrates and for the 0.5-micron grooves substrates with 1% S. For the
      migration studies, bone cells were plated first onto 5-mm nitrocellulose disks
      that were attached to standard Petri dishes using a plasma clot. At confluence,
      the disks were removed aseptically and placed on the replicas. The cellular area
      occupied as a result of the outward migration of the bone cells was measured
      after 4 days of culture using an image analysis system. An average velocity for
      the leading edge of bone cell populations on each of the nine MBSs was
      calculated: Cells on surfaces with either 1% S or 5.0-microns grooves displayed
      significantly higher velocities than did the control cultures. A significant
      interaction effect between chemistry and morphology was observed. The
      biosynthetic and migratory responses of in vitro cultures of bone cells were not
      predictable from the observations of the cellular responses to the individual
      features, but appeared to depend on cellular responses to more than one substrate
      factor.

PMID- 8567710
TI  - Extracellular matrix interactions during the in vivo degradation of collagen
      membranes in the rat skin: immunohistochemical distribution of collagen types IV,
      V, and VI.
AB  - The role of collagen implant material (CIM) in periodontology is of considerable
      interest to the clinical dentist because of the capacity of connective tissue
      (CT) regeneration and partial prevention of epithelial cell migration onto the
      root surface. The aim of this study was to demonstrate alterations of the CT
      matrix after the use of CIM in subcutaneous pockets in the rat skin. We used 15
      rats in this study. After sedation, two subcutaneous pockets (2 cm in length)
      were surgically made in the animals' backs. Collagen membranes were implanted in
      one of the two pockets (test site). The other pocket served as control. Then, 4,
      7, 14, 21, and 28 days after implantation, the animals were sacrificed and
      biopsies preserved for histologic and immunohistochemical examination. Incubation
      with antibodies against CT matrix components (collagen type IV, V, and VI) were
      used for immunostaining. Histologically, the CIM was migrated by inflammatory
      cells in the first 7 days. Newly formed fibroblasts and blood vessels (BV) were
      present 14 days postimplantation. Collagen type IV was localized in the basement
      membranes of the epithelium, BV, and nerves. An increase in the BV amount was
      demonstrated around (and later in) the implant material. Collagen type V was
      found in a filament pattern of distribution and was inserted into the implant
      after 4 weeks of healing. Collagen type VI showed a microfibrillar pattern of
      distribution with a delayed formation in the graft mass. The data showed the
      alterations of the matrix after implantation of collagen type I membranes in the
      rat skin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567711
TI  - Study of aging of silicone rubber biomaterials with NMR.
AB  - Multinuclear nuclear magnetic resonance (NMR) spectroscopy (29Si, 13C, 1H) is
      used to characterize the aging process of silicone rubber-based biomaterials in a
      rat model. 1H NMR relaxation measurements (spin-lattice, T1, and spin-spin, T2,
      relaxation times) were performed to better understand the molecular dynamics of
      polysiloxane chains in implants. After 1 year of implantation in animals, changes
      in the 1H T2 relaxation times and the NMR spectra were observed in
      polydimethylsiloxane, Silastic sheets and chin implants, while these measurements
      remain unchanged in finger joints. Very small amounts of fat were detected in all
      types of silicone rubber implants at the end of the implantation period. This
      work shows that free silicone migrates from the implants to adjacent tissues and
      distant sites, such as spleen or liver, and is chemically modified.

PMID- 8567712
TI  - Local delivery of indomethacin by a polyorthoester inhibits reossification of
      experimental bone defects.
AB  - Inhibition of orthotopic reossification after surgical removal of bone is
      sometimes indicated and may be accomplished by implantation of interpositional
      materials or by systemic administration of indomethacin. However, implantation of
      nonresorbable foreign material may induce a chronic inflammation and predispose
      to infections; and systemic administration of indomethacin may induce systemic
      adverse effects. We studied the effect of local delivery of indomethacin by a
      bioerodible polyorthoester on the reossification of segmental defects of the
      radius in rats. We divided 45 Wistar rats into three groups, A-C. A 3.5 mm-long
      middiaphyseal osteoperiosteal resection of the right radius was made in each rat.
      The defect was filled with 15 mg of polyorthoester with 5% indomethacin in group
      A and 15 mg of polyorthoester without drug in group B. No material was implanted
      in the defects in the group C rats. The rats were killed 50 days postoperatively.
      The mean area of the residual defects were greater in the defects with the
      polyorthoester with 5% indomethacin compared with defects with polyorthoester
      without drug or without implant as judged by computer-assisted area measurements
      on radiographs. By light microscopy, no inflammation was seen and only traces of
      the polyorthoester could be detected in the defects filled with the
      polyorthoester with or without indomethacin. The results of this study suggest
      that the polyorthoester may be used as a bioerodible system for local delivery of
      indomethacin to inhibit reossification of skeletal defects without tissue
      reaction, unabsorbed carrier, or systemic effects.

PMID- 8567713
TI  - Articular cartilage repair using allogeneic perichondrocyte-seeded biodegradable
      porous polylactic acid (PLA): a tissue-engineering study.
AB  - Efforts to expand treatment options for articular cartilage repair have
      increasingly focused on the implantation of cell-polymer constructs. The purpose
      of this study is to determine the suitability of porous D,D-L,L-polylactic acid
      as a carrier for delivering repair cells obtained from rib perichondrium into
      full-thickness articular cartilage defects. In vitro characterization of
      perichondrocyte-polylactic acid composite grafts was combined with in vivo
      assessment of the early articular cartilage repair in a clinically relevant
      model. Using a fluorescent double-stain protocol to visualize live and dead cells
      in situ, primary cells cultured from perichondrium were found to be capable of
      attaching to and surviving within a porous D,D-L,L-polylactic acid matrix. These
      perichondrocyte-polylactic acid composite grafts were then implanted within
      osteochondral defects drilled into the left medial femoral condyles of 16 adult
      New Zealand white rabbits. Experimental animals were sacrificed 6 weeks after
      implantation and the repair tissue was evaluated grossly, histologically, and
      biochemically. Grossly, 96% (15/16) of the experimental animals demonstrated
      repairs consisting of a smooth, firm neocartilage which appeared similar in color
      and texture to the surrounding articular surface. Matrix staining for
      cartilaginous protein was seen surrounding chondrocyte-like cells in the
      cartilage regions of the repair. Cellular alignment was found to be related to
      scaffold architecture. These results suggest that scaffolds composed of porous
      D,D-L,L-polylactic acid support the growth of cartilaginous repair tissue and are
      compatible with both in vitro and in vivo survival of chondrogenic cells.

PMID- 8567714
TI  - Polysulphone inhibits final differentiation steps of osteogenesis in vitro.
AB  - Biocompatibility is an important factor in the development of orthopedic implants
      as well as in the development of new tissue culture devices. Polysulphone has
      been used for orthopedic implants because of its mechanical properties, ease of
      sterilization, molding capacity, and biocompatibility. Therefore, polysulphone
      has been chosen as the prime material for the construction of tissue culture
      devices to be used for the cultivation of osteogenic cells (preosteoblast-like
      MN7 cells and primary bone marrow fragments), as well as complete fetal long bone
      explants under space flight conditions. Whereas polysulphone did not interfere
      with the proliferation in early stages of bone-forming cells, we show that
      leachable factors within the polysulphone polymer prevented the final steps of
      matrix formation as measured by collagen synthesis and matrix mineralization.
      These data argue against polysulphone as a material for orthopedic implants.

PMID- 8567715
TI  - Chaperonin-mediated folding of actin and tubulin.

PMID- 8567716
TI  - Dictyostelium myosin heavy chain kinase A regulates myosin localization during
      growth and development.
AB  - Phosphorylation of the Dictyostelium myosin II heavy chain (MHC) has a key role
      in regulating myosin localization in vivo and drives filament disassembly in
      vitro. Previous molecular analysis of the Dictyostelium myosin II heavy chain
      kinase (MHCK A) gene has demonstrated that the catalytic domain of this enzyme is
      extremely novel, showing no significant similarity to the known classes of
      protein kinases (Futey, L. M., Q. G. Medley, G. P. Cote, and T. T. Egelhoff.
      1995. J. Biol. Chem. 270:523-529). To address the physiological roles of this
      enzyme, we have analyzed the cellular consequences of MHCK A gene disruption
      (mhck A- cells) and MHCK A overexpression (MHCK A++ cells). The mhck A- cells are
      viable and competent for tested myosin-based contractile events, but display
      partial defects in myosin localization. Both growth phase and developed mhck A-
      cells show substantially reduced MHC kinase activity in crude lysates, as well as
      significant overassembly of myosin into the Triton-resistant cytoskeletal
      fractions. MHCK A++ cells display elevated levels of MHC kinase activity in crude
      extracts, and show reduced assembly of myosin into Triton-resistant cytoskeletal
      fractions. MHCK A++ cells show reduced growth rates in suspension, becoming large
      and multinucleated, and arrest at the mound stage during development. These
      results demonstrate that MHCK A functions in vivo as a protein kinase with
      physiological roles in regulating myosin II localization and assembly in
      Dictyostelium cells during both growth and developmental stages.

PMID- 8567717
TI  - The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a
      mitotic checkpoint.
AB  - M-phase checkpoints inhibit cell division when mitotic spindle function is
      perturbed. Here we show that the Saccharomyces cerevisiae MPS1 gene product, an
      essential protein kinase required for spindle pole body (SPB) duplication (Winey
      et al., 1991; Lauze et al., 1995), is also required for M-phase check-point
      function. In cdc31-2 and mps2-1 mutants, conditional failure of SPB duplication
      results in cell cycle arrest with high p34CDC28 kinase activity that depends on
      the presence of the wild-type MAD1 checkpoint gene, consistent with checkpoint
      arrest of mitosis. In contrast, mps1 mutant cells fail to duplicate their SPBs
      and do not arrest division at 37 degrees C, exhibiting a normal cycle of p34CDC28
      kinase activity despite the presence of a monopolar spindle. Double mutant cdc31
      2, mps1-1 cells also fail to arrest mitosis at 37 degrees C, despite having SPB
      structures similar to cdc31-2 single mutants as determined by EM analysis. Arrest
      of mitosis upon microtubule depolymerization by nocodazole is also conditionally
      absent in mps1 strains. This is observed in mps1 cells synchronized in S phase
      with hydroxyurea before exposure to nocodazole, indicating that failure of
      checkpoint function in mps1 cells is independent of SPB duplication failure. In
      contrast, hydroxyurea arrest and a number of other cdc mutant arrest phenotypes
      are unaffected by mps1 alleles. We propose that the essential MPS1 protein kinase
      functions both in SPB duplication and in a mitotic checkpoint monitoring spindle
      integrity.

PMID- 8567718
TI  - Initial triggering of M-phase in starfish oocytes: a possible novel component of
      maturation-promoting factor besides cdc2 kinase.
AB  - G2-phase-arrested immature starfish oocytes contain inactive cdc2 kinase and
      cdc25 phosphatase, and an inactivator for cdc2 kinase. In this system, we have
      studied how the regulatory balance is apped toward the initial activation of cdc2
      kinase. During the hormone-dependent period (Guerrier, P., and M. Doree, 1975.
      Dev. Biol. 47:341-348), p34cdc2 and cdc25 protein are already converted, though
      not fully, to active forms, whereas the inactivators for cdc2 kinase and cdc25
      phosphatase are able to exhibit their activities if the hormone were removed. We
      produced "triggered oocytes," in which due to a neutralizing anticdc25 antibody,
      the activation of cdc2 kinase is prevented out cdc25 protein is phosphorylated
      slightly after the maturation-inducing hormonal stimulus. In contrast to control
      immature oocytes, in triggered oocytes the injected cdc2 kinase is not
      inactivated, and accordingly the level of cdc2 kinase activity required for
      meiosis reinitiation is much less. These results imply the presence of a cdc2
      kinase activity-independent process(es) that suppresses the inactivator for cdc2
      kinase and initially phosphorylates cdc25 protein, although this process is
      reversible during the initial activation of cdc2 kinase. At the most initial
      triggering of M-phase, the cdc2 kinase activity-independent process might trip
      the switch leading to the initial activation of cdc2 kinase. Thereafter, in
      parallel, the cdc2 kinase-dependent feedback loops described by others may cause
      further increase in cdc2 kinase activity. We propose that a putative suppressor,
      which downregulates the inactivator for cdc2 kinase independently of nuclear
      components, might be a previously unrecognized component of maturation-promoting
      factor.

PMID- 8567719
TI  - BED1, a gene encoding a galactosyltransferase homologue, is required for
      polarized growth and efficient bud emergence in Saccharomyces cerevisiae.
AB  - The ellipsoidal shape of the yeast Saccharomyces cerevisiae is the result of
      successive isotropic/apical growth switches that are regulated in a cell cycle
      dependent manner. It is thought that growth polarity is governed by the
      remodeling of the actin cytoskeleton that is itself under the control of the cell
      cycle machinery. The cell cycle and the morphogenesis cycle are tightly coupled
      and it has been recently suggested that a morphogenesis/polarity checkpoint
      control monitors bud emergence in order to maintain the coupling of these two
      events (Lew, D. J., and S. I. Reed. 1995. J. Cell Biol. 129:739-749). During a
      screen based on the inability of cells impaired in the budding process to survive
      when the morphogenesis checkpoint control is abolished, we identified and
      characterized BED1, a new gene that is required for efficient budding. Cells
      carrying a disrupted allele of BED1 no longer have the wild-type ellipsoidal
      shape characteristic of S. cerevisiae, are larger than wild-type cells, are
      deficient in bud emergence, and depend upon an intact morphogenesis checkpoint
      control to survive. These cells show defects in polarized growth despite the fact
      that the actin cytoskeleton appears normal. Our results suggest that Bed1 is a
      type II membrane protein localized in the endoplasmic reticulum. BED1 is
      significantly homologous to gma12+, a S. pombe gene coding for an alpha-1,2,
      galactosyltransferase, suggesting that glycosylation of specific proteins or
      lipids could be important for signaling in the switch to polarized growth and in
      bud emergence.

PMID- 8567720
TI  - A nontetrameric species is the major soluble form of keratin in Xenopus oocytes
      and rabbit reticulocyte lysates.
AB  - Inside the interphase cell, approximately 5% of the total intermediate filament
      protein exists in a soluble form. Past studies using velocity gradient
      sedimentation (VGS) indicate that soluble intermediate filament protein exists as
      an approximately 7 S tetrameric species. While studying intermediate filament
      assembly dynamics in the Xenopus oocyte, we used both VGS and size-exclusion
      chromatography (SEC) to analyze the soluble form of keratin. Previous studies
      (Coulombe, P. A., and E. Fuchs. 1990. J. Cell Biol. 111:153) report that
      tetrameric keratins migrate on SEC with an apparent molecular weight of
      approximately 150,000; the major soluble form of keratin in the oocyte, in
      contrast, migrates with an apparent molecular weight of approximately 750,000.
      During oocyte maturation, the keratin system disassembles into a soluble form
      (Klymkowsky, M. W., L. A. Maynell, and C. Nislow. 1991. J. Cell Biol. 114:787)
      and the amount of the 750-kD keratin complex increases dramatically.
      Immunoprecipitation analysis of soluble keratin from matured oocytes revealed the
      presence of type I and type II keratins, but no other stoichiometrically
      associated polypeptides, suggesting that the 750-kD keratin complex is composed
      solely of keratin. To further study the formation of the 750-kD keratin complex,
      we used rabbit reticulocyte lysates (RRL). The 750-kD keratin complex was formed
      in RRLs contranslating type I and type II Xenopus keratins, but not when lysates
      translated type I or type II keratin RNAs alone. The 750-kD keratin complex could
      be formed posttranslationally in an ATP-independent manner when type I and type
      II keratin translation reactions were mixed. Under conditions of prolonged
      incubation, such as occur during VGS analysis, the 750-kD keratin complex
      disassembled into a 7 S (by VGS), 150-kD (by SEC) form. In urea denaturation
      studies, the 7 S/150-kD form could be further disassembled into an 80-kD species
      that consists of cofractionating dimeric and monomeric keratin. Based on these
      results, the 750-kD species appears to be a supratetrameric complex of keratins
      and is the major, soluble form of keratin in both prophase and M-phase oocytes,
      and RRL reactions.

PMID- 8567721
TI  - VAMP/synaptobrevin isoforms 1 and 2 are widely and differentially expressed in
      nonneuronal tissues.
AB  - VAMP/synaptobrevin is part of the synaptic vesicle docking and fusion complex and
      plays a central role in neuroexocytosis. Two VAMP (vesicle-associated membrane
      protein) isoforms are expressed in the nervous system and are differently
      distributed among the specialized parts of the tissue. Here, VAMP-1 and -2 are
      shown to be present in all rat tissues tested, including kidney, adrenal gland,
      liver, pancreas, thyroid, heart, and smooth muscle. The two isoforms are
      differentially expressed in various tissues and their level may depend on
      differentiation. VAMP-1 is restricted to exocrine pancreas and to kidney tubular
      cells, whereas VAMP-2 is the predominant isoform present in Langerhans islets and
      in glomerular cells. Both isoforms show a patchy vesicular intracellular
      distribution in confocal microscopy. The present results provide evidence for the
      importance of neuronal VAMP proteins in the physiology of all cells.

PMID- 8567722
TI  - Lysophosphatidic acid and bFGF control different modes in proliferating
      myoblasts.
AB  - Myogenic cells provide excellent in vitro models for studying the cell growth and
      differentiation. In this study we report that lysophosphatidic acid (LPA), a
      bioactive phospholipid contained in serum, stimulates the growth and inhibits the
      differentiation of mouse C2C12 myoblast cells, in a distinct manner from basic
      fibroblast growth factor (bFGF) whose mitotic and anti-differentiation actions
      have been well investigated. These actions of LPA were both blocked by pertussis
      toxin, suggesting the involvement of Gi class of G proteins, whereas bFGF acts
      through receptor tyrosine kinases. Detailed analysis revealed that LPA and bFGF
      act differently in regulating the myogenic basic helix-loop-helix (bHLH)
      proteins, the key players in myogenic differentiation process. LPA stimulates the
      proliferation of undifferentiated myoblasts allowing the continued expression of
      MyoD, but in contrast, bFGF does so with the MyoD expression suppressed at the
      mRNA level. Both compounds maintain the myf-5 expression, and suppress the
      myogenin expression. In addition, while LPA did not inhibit cell-cell contact
      induced differentiation, bFGF strongly inhibited this process. Furthermore, LPA
      and bFGF act cooperatively in their mitogenic and anti-differentiation abilities.
      These findings indicate that LPA and bFGF differently stimulate intracellular
      signaling pathways, resulting in proliferating myoblasts each bearing a distinct
      expression pattern of myogenic bHLH proteins and distinct differentiation
      potentials in response to cell-cell contact, and illustrate the biological
      significance of Gi-mediated and tyrosine kinase-mediated signals.

PMID- 8567723
TI  - Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like
      phenotype.
AB  - The development of the skeleton requires the coordinated activities of bone
      forming osteoblasts and bone-resorbing osteoclasts. The activities of these two
      cell types are likely to be regulated by TGF-beta, which is abundant in bone
      matrix. We have used transgenic mice to evaluate the role of TGF-beta 2 in bone
      development and turnover. Osteoblast-specific overexpression of TGF-beta 2 from
      the osteocalcin promoter resulted in progressive bone loss associated with
      increases in osteoblastic matrix deposition and osteoclastic bone resorption.
      This phenotype closely resembles the bone abnormalities seen in human
      hyperparathyroidism and osteoporosis. Furthermore, a high level of TGF-beta 2
      overexpression resulted in defective bone mineralization and severe hypoplasia of
      the clavicles, a hallmark of the developmental disease cleidocranial dysplasia.
      Our results suggest that TGF-beta 2 functions as a local positive regulator of
      bone remodeling and that alterations in TGF-beta 2 synthesis by bone cells, or in
      their responsiveness to TGF-beta 2, may contribute to the pathogenesis of
      metabolic bone disease.

PMID- 8567724
TI  - A novel class of clathrin-coated vesicles budding from endosomes.
AB  - Clathrin-coated vesicles transport selective integral membrane proteins from the
      plasma membrane to endosomes and from the TGN to endosomes. Recycling of proteins
      from endosomes to the plasma membrane occurs via unidentified vesicles. To study
      this pathway, we used a novel technique that allows for the immunoelectron
      microscopic examination of transferrin receptor-containing endosomes in
      nonsectioned cells. Endosomes were identified as separate discontinuous tubular
      vesicular entities. Each endosome was decorated, mainly on the tubules, with many
      clathrin-coated buds. Endosome-associated clathrin-coated buds were discerned
      from plasma membrane-derived clathrin-coated vesicles by three criteria: size (60
      nm and 100 nm, respectively), continuity with endosomes, and the lack of labeling
      for alpha-adaptin. They were also distinguished from TGN-derived clathrin-coated
      vesicles by their location at the periphery of the cell, size, and the lack of
      labeling for gamma-adaptin. In the presence of brefeldin A, a large continuous
      endosomal network was formed. Transferrin receptor recycling as well as the
      formation of clathrin-coated pits at endosomes was inhibited in the presence of
      brefeldin A. Together with the localization of transferrin receptors at endosome
      associated buds, this indicates that a novel class of clathrin-coated vesicles
      serves an exit pathway from endosomes. The target organelles for endosome-derived
      clathrin-coated vesicles remain, however, to be identified.

PMID- 8567726
TI  - Beta 1 integrin-dependent and -independent polymerization of fibronectin.
AB  - The mouse cell line GD25, which lacks expression of the beta 1 family of integrin
      heterodimers due to disruption of the beta 1 integrin subunit gene, was used for
      expression of full-length cDNA coding for splice variant A of the mouse beta 1
      integrin subunit. In a stably transformed clone (GD25-beta 1A), the expressed
      protein was found to form functional heterodimeric receptors together with the
      subunits alpha 3, alpha 5, and alpha 6. Both GD25 and GD25-beta 1A attached to
      fibronectin and formed focal contacts which contained alpha v beta 3, but no
      detectable alpha 5 beta 1A. The presence of GRGDS peptide allowed alpha 5 beta 1A
      to locate to focal contacts of GD25-beta 1A cultured on fibronectin, while the
      beta 1-null GD25 cells were unable to attach under these conditions. Affinity
      chromatography revealed that alpha 5 beta 1A and alpha v beta 3 could bind to a
      large cell-binding fragment of fibronectin. alpha 5 beta 1A strongly promoted
      polymerization of fibronectin into a fibrillar network on top of the cells.
      Whereas little alpha v beta 3 was colocalized with the fibronectin fibrils in
      GD25-beta 1A cells, this integrin was able to support fibronectin fibril
      polymerization in GD25 cells. However, the alpha v beta 3-induced polymerization
      was less efficient and occurred mainly in dense cultures of the GD25 cells. Thus,
      while both alpha 5 beta 1A and alpha v beta 3 are able to support adhesion to
      fibronectin, alpha v beta 3 dominates in the formation of focal contacts, and
      alpha 5 beta 1A has a prime function in fibronectin matrix assembly. This is the
      first report on fibronectin matrix assembly in the absence of beta 1 integrins.

PMID- 8567725
TI  - Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization
      at junctional structures and signaling potential in nonmuscle cells.
AB  - The cytoplasmic domains of integrins provide attachment of these extracellular
      matrix receptors to the cytoskeleton and play a critical role in integrin
      mediated signal transduction. In this report we describe the identification,
      expression, localization, and initial functional characterization of a novel form
      of beta 1 integrin, termed beta 1D. This isoform contains a unique alternatively
      spliced cytoplasmic domain of 50 amino acids, with the last 24 amino acids
      encoded by an additional exon. Of these 24 amino acids, 11 are conserved when
      compared to the beta 1A isoform, but 13 are unique (Zhidkova, N. I., A. M.
      Belkin, and R. Mayne. 1995. Biochem. Biophys. Res. Commun. 214:279-285; van der
      Flier, A., I. Kuikman, C. Baudoin, R, van der Neuf, and A. Sonnenberg. 1995. FEBS
      Lett. 369:340-344). Using an anti-peptide antibody against the beta 1D integrin
      subunit, we demonstrated that the beta 1D isoform is synthesized only in skeletal
      and cardiac muscles, while very low amounts of beta 1A were detected by
      immunoblot in striated muscles. Whereas beta 1A could not be detected in adult
      skeletal muscle fibers and cardiomyocytes by immunofluorescence, beta 1D was
      localized to the sarcolemma of both cell types. In skeletal muscle, beta 1D was
      concentrated in costameres, myotendinous, and neuromuscular junctions. In cardiac
      muscle this beta 1 isoform was found in costamers and intercalated discs. beta 1D
      was associated with alpha 7A and alpha 7B in adult skeletal muscle. In
      cardiomyocytes of adult heart, alpha 7B was the major partner for the beta 1D
      isoform. beta 1D could not be detected in proliferating C2C12 myoblasts, but it
      appeared immediately after myoblast fusion and its amount continued to rise
      during myotube growth and maturation. In contrast, expression of the beta 1A
      isoform was downregulated during myodifferentiation in culture and it was
      completely displaced by beta 1D in mature differentiated myotubes. We also
      analyzed some functional properties of the beta 1D integrin subunit. Expression
      of human beta 1D in CHO cells led to its localization at focal adhesions.
      Clustering of this integrin isoform on the cell surface stimulated tyrosine
      phosphorylation of pp125FAK (focal adhesion kinase) and caused transient
      activation of mitogen-activated protein (MAP) kinases. These data indicate that
      beta 1D and beta 1A integrin isoforms are functionally similar with regard to
      integrin-mediated signaling.

PMID- 8567727
TI  - Extracellular matrix alters PDGF regulation of fibroblast integrins.
AB  - Extracellular matrix (ECM) and growth factors are potent regulators of cell
      phenotype. These biological mediators of cellular responses are potentially
      interactive and as such could drive cells through progressive phenotypes to
      create new tissue as in morphogenesis and wound repair. In fact, ECM composition
      changes during tissue formation accompanied by alterations in cell growth and
      migration. How alterations in the ECM regulate cell activities is poorly defined.
      To address this question in wound repair, we cultured normal human dermal skin
      fibroblasts in relaxed collagen gels, fibronectin-rich cultures or stressed
      fibrin gels, and stressed collagen gels to model normal dermis, early wound
      provisional matrix, and late granulation tissue, respectively. Integrin subunits,
      alpha 2, alpha 3, and alpha 5, that define receptor specificity for collagen and
      provisional matrix, respectively, were measured at mRNA steady-state level before
      and after stimulation with platelet-derived growth factor-BB (PDGF-BB), a potent
      mitogen and chemoattractant for fibroblasts. Fibronectin-rich cultures and fibrin
      gels supported PDGF-BB induction of alpha 3 and alpha 5 mRNA. In contrast, both
      stressed and relaxed collagen attenuated these responses while promoting maximal
      alpha 2 mRNA expression. Posttranscriptional regulation was an important
      mechanism in this differential response. Together PDGF-BB and collagen gels
      promoted alpha 2, but not alpha 3 and alpha 5, mRNA stability. Conversely, when
      fibroblasts were in fibronectin-rich cultures, PDGF-BB promoted alpha 3 and alpha
      5, but not alpha 2, mRNA stability. We suggest that ECM alterations during wound
      healing or any new tissue formation cause cells to respond differently to
      repeated growth factor stimuli. An ordered progression of cell phenotypes
      results, ultimately consummating tissue repair or morphogenesis.

PMID- 8567728
TI  - Endocytosis of GPI-linked membrane folate receptor-alpha.
AB  - GPI-linked membrane folate receptors (MFRs) have been implicated in the receptor
      mediated uptake of reduced folate cofactors and folate-based chemotherapeutic
      drugs. We have studied the biosynthetic transport to and internalization of MFR
      isoform alpha in KB-cells. MFR-alpha was synthesized as a 32-kD protein and
      converted in a maturely glycosylated 36-38-kD protein 1 h after synthesis. 32-kD
      MFR-alpha was completely soluble in Triton X-100 at 0 degree C. In contrast, only
      33% of the 36-38-kD species could be solubilized at these conditions whereas
      complete solubilization was obtained in Triton X-100 at 37 degrees C or in the
      presence of saponin at 0 degree C. Similar solubilization characteristics were
      found when MFR-alpha at the plasma membrane was labeled with a crosslinkable 125I
      labeled photoaffinity-analog of folic acid as a ligand. Triton X-100-insoluble
      membrane domains containing MFR-alpha could be separated from soluble MFR-alpha
      on sucrose flotation gradients. Only Triton X-100 soluble MFR-alpha was
      internalized from the plasma membrane. The reduced-folate-carrier, an integral
      membrane protein capable of translocating (anti-)folates across membranes, was
      completely excluded from the Triton X-100-resistant membrane domains.
      Internalized MFR-alpha recycled slowly to the cell surface during which it
      remained soluble in Triton X-100 at 0 degree C. Using immunoelectron microscopy,
      we found MFR-alpha along the entire endocytic pathway: in clathrin-coated buds
      and vesicles, and in small and large endosomal vacuoles. In conclusion, our data
      indicate that a large fraction, if not all, of internalizing MFR-alpha bypasses
      caveolae.

PMID- 8567729
TI  - Phagosome-lysosome fusion is a calcium-independent event in macrophages.
AB  - Phagosome-lysosome membrane fusion is a highly regulated event that is essential
      for intracellular killing of microorganisms. Functionally, it represents a form
      of polarized regulated secretion, which is classically dependent on increases in
      intracellular ionized calcium ([Ca2+]i). Indeed, increases in [Ca2+]i are
      essential for phagosome-granule (lysosome) fusion in neutrophils and for
      lysosomal fusion events that mediate host cell invasion by Trypanosoma cruzi
      trypomastigotes. Since several intracellular pathogens survive in macrophage
      phagosomes that do not fuse with lysosomes, we examined the regulation of
      phagosome-lysosome fusion in macrophages. Macrophages (M phi) were treated with
      12.5 microM bis-(2-amino-S-methylphenoxy) ethane-N,N,N',N',-tetraacetic acid
      tetraacetoxymethyl ester (MAPT/AM), a cell-permeant calcium chelator which
      reduced resting cytoplasmic [Ca2+]; from 80 nM to < or = 20 nM and completely
      blocked increases in [Ca2+]i in response to multiple stimuli, even in the
      presence of extracellular calcium. Subsequently, M phi phagocytosed serum
      opsonized zymosan, staphylococci, or Mycobacterium bovis. Microbes were
      enumerated by 4',6-diamidino-2-phenylindole, dihydrochloride (DAPI) staining, and
      phagosome-lysosome fusion was scored using both lysosome-associated membrane
      protein (LAMP-1) as a membrane marker and rhodamine dextran as a content marker
      for lysosomes. Confirmation of phagosome-lysosome fusion by electron microscopy
      validated the fluorescence microscopy findings. We found that phagosome-lysosome
      fusion in M phi occurs noramlly at very low [Ca2+]i (< or = 20 nM). Kinetic
      analysis showed that in M phi none of the steps leading from particle binding to
      eventual phagosome-lysosome fusion are regulated by [Ca2+]i in a rate-limiting
      way. Furthermore, confocal microscopy revealed no difference in the intensity of
      LAMP-1 immunofluorescence in phagolysosome membranes in calcium-buffered vs.
      control macrophages. We conclude that neither membrane recognition nor fusion
      events in the phagosomal pathway in macrophages are dependent on or regulated by
      calcium.

PMID- 8567730
TI  - Assembly of the nuclear pore: biochemically distinct steps revealed with NEM, GTP
      gamma S, and BAPTA.
AB  - A key event in nuclear formation is the assembly of functional nuclear pores. We
      have used a nuclear reconstitution system derived from Xenopus eggs to examine
      the process of nuclear pore assembly in vitro. With this system, we have
      identified three reagents which interfere with nuclear pore assembly, NEM, GTP
      gamma S, and the Ca++ chelator, BAPTA. These reagents have allowed us to
      determine that the assembly of a nuclear pore requires the prior assembly of a
      double nuclear membrane. Inhibition of nuclear vesicle fusion by pretreatment of
      the membrane vesicle fraction with NEM blocks pore complex assembly. In contrast,
      NEM treatment of already fused double nuclear membranes does not block pore
      assembly. This indicates that NEM inhibits a single step in pore assembly--the
      initial fusion of vesicles required to form a double nuclear membrane. The
      presence of GTP gamma S blocks pore assembly at two distinct steps, first by
      preventing fusion between nuclear vesicles, and second by blocking a step in pore
      assembly that occurs on already fused double nuclear membranes. Interestingly,
      when the Ca2+ chelator BAPTA is added to a nuclear assembly reaction, it only
      transiently blocks nuclear vesicle fusion, but completely blocks nuclear pore
      assembly. This results in the formation of a nucleus surrounded by a double
      nuclear membrane, but devoid of nuclear pores. To order the positions at which
      GTP gamma S and BAPTA interfere with pore assembly, a novel anchored nuclear
      assembly assay was developed. This assay revealed that the BAPTA-sensitive step
      in pore assembly occurs after the second GTP gamma S-sensitive step. Thus,
      through use of an in vitro nuclear reconstitution system, it has been possible to
      biochemically define and order multiple steps in nuclear pore assembly.

PMID- 8567731
TI  - A new chloroplast protein import intermediate reveals distinct translocation
      machineries in the two envelope membranes: energetics and mechanistic
      implications.
AB  - Chloroplast protein import presents a complex membrane traversal problem:
      precursor proteins must cross two envelope membranes to reach the stromal
      compartment. This work characterizes a new chloroplast protein import
      intermediate which has completely traversed the outer envelope membrane but has
      not yet reached the stroma. The existence of this intermediate demonstrates that
      distinct protein transport machineries are present in both envelope membranes,
      and that they are able to operate independently of one another under certain
      conditions. Energetic characterization of this pathway led to the identification
      of three independent energy-requiring steps: binding of the precursor to the
      outer envelope membrane, outer membrane transport, and inner membrane transport.
      Localization of the sites of energy utilization for each of these steps, as well
      as their respective nucleotide specificities, suggest that three different
      ATPases mediate chloroplast envelope transport.

PMID- 8567732
TI  - Identification and localization of an actin-binding motif that is unique to the
      epsilon isoform of protein kinase C and participates in the regulation of
      synaptic function.
AB  - Individual isoforms of the protein kinase C (PKC) family of kinases may have
      assumed distinct responsibilities for the control of complex and diverse cellular
      functions. In this study, we show that an isoform specific interaction between
      PKC epsilon and filamentous actin may serve as a necessary prelude to the
      enhancement of glutamate exocytosis from nerve terminals. Using a combination of
      cosedimentation, overlay, and direct binding assays, we demonstrate that
      filamentous actin is a principal anchoring protein for PKC epsilon within intact
      nerve endings. The unusual stability and direct nature of this physical
      interaction indicate that actin filaments represent a new class of PKC-binding
      protein. The binding of PKC epsilon to actin required that the kinase be
      activated, presumably to expose a cryptic binding site that we have identified
      and shown to be located between the first and second cysteine-rich regions within
      the regulatory domain of only this individual isoform of PKC. Arachidonic acid
      (AA) synergistically interacted with diacylglycerol to stimulate actin binding to
      PKC epsilon. Once established, this protein-protein interaction securely anchored
      PKC epsilon to the cytoskeletal matrix while also serving as a chaperone that
      maintained the kinase in a catalytically active conformation. Thus, actin appears
      to be a bifunctional anchoring protein that is specific for the PKC epsilon
      isoform. The assembly of this isoform-specific signaling complex appears to play
      a primary role in the PKC-dependent facilitation of glutamate exocytosis.

PMID- 8567734
TI  - Brachial plexus surgery. An historical perspective.
AB  - Clinical observations on brachial plexus palsy belong to the last decades of the
      19th century. True brachial plexus surgery is even more recent, starting with the
      beginning of this century. Surgical endeavors on the plexus have been varied and
      have met with alternating fortunes, undertaken by surgeons in a fascinating blend
      of sheer enthusiasm and deep pessimism.

PMID- 8567733
TI  - Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte
      progenitor.
AB  - We analyzed the role of Fyn tyrosine kinase in cell cycle progression of B
      lymphocyte progenitor (pro B cell). Whereas there were no substantial defects in
      the intramarrow B cell genesis in the fyn(-) mouse, and long-term proliferation
      of fyn(-) pro B cells was maintained in vitro under a serum containing culture
      condition, the cell cycle was arrested at G2/M upon serum deprivation.
      Morphological analyses demonstrated that the cytokinesis of fyn(-) pro B cells
      was retarded in the presence of serum and that the entry of fyn(-) pro B cells
      into late telophase was completely blocked under the serum-free condition. In
      contrast, the earlier phases of mitosis of fyn(-) pro B cells proceeded normally
      without FCS. This failure to initiate late telophase resulted in the accumulation
      of elliptical binucleated cells that might be the outcome of the nuclear division
      without cytokinesis. Consistent with this defect in the progression of
      cytokinesis, Fyn was localized in the midspace of dividing pro B cells at
      anaphase. These results suggested that Fyn localizes at the midspace of dividing
      pro B cells and regulates the progression of cytokinesis.

PMID- 8567735
TI  - Algimantas Otonas Narakas (1927-1993). A biographical note.

PMID- 8567736
TI  - Anatomic observations on the suprascapular nerve.

PMID- 8567737
TI  - Advanced imaging techniques of the brachial plexus.
AB  - The brachial plexus is a complex structure that arises from nerve roots in the
      neck and terminates by dividing into peripheral nerves in the axilla. Imaging the
      brachial plexus can be difficult because of this anatomy. MRI now is the imaging
      modality of choice in the evaluation of brachial plexopathy. T1-weighted axial
      and oblique coronal images supplemented by T-2 weighted or STIR images are a
      standard protocol. MRI can be used to diagnose nerve root avulsion, neuromas,
      tumor, and radiation fibrosis.

PMID- 8567738
TI  - Electrodiagnosis in the management of brachial plexus surgery.
AB  - A few pre and intraoperative neurophysiological tests offer valuable information
      in the diagnosis and functional evaluation of brachial plexus injury. The tests
      and the questions they answer can guide the surgeon's decision about whether to
      perform neurolysis or an interpositional graft.

PMID- 8567739
TI  - An approach to obstetrical brachial plexus injuries.
AB  - The approach of one clinic to the early evaluation of the infant with an
      obstetrical brachial plexus palsy has been presented. The need for a reproducible
      and standardized grading system has been identified. The natural history of these
      lesions will be better understood as further studies elucidate key principles.
      The final goals are the precise prognostication of natural outcome and the early
      prediction of the need for surgical intervention.

PMID- 8567740
TI  - Long-term evaluation of brachial plexus surgery in obstetrical palsy.
AB  - The author reviews the long-term results of a large series of obstetrical
      brachial plexuses. The results of direct repair and secondary tendon transfers
      are reviewed.

PMID- 8567741
TI  - Palliative surgical procedures to restore shoulder function in obstetric brachial
      palsy. Critical analysis of Narakas' series.
AB  - Dr. Narakas intended to study a series of 61 cases of shoulder sequelae of
      obstetric palsy. His vast experience would have enriched our clinical knowledge
      of this ailment. The authors carry on with that study to clarify his therapeutic
      approach and share the benefit of his experience.

PMID- 8567742
TI  - A management approach for secondary shoulder and forearm deformities following
      obstetrical brachial plexus injury.
AB  - This article provides an overview of the historical perspectives of shoulder
      deformity. Biomechanical considerations are discussed, as well as the authors'
      personal approach to these types of injuries.

PMID- 8567743
TI  - Special rehabilitation considerations in the management of obstetrical brachial
      plexus injuries.

PMID- 8567744
TI  - Traumatic brachial plexus lesions in the adult. Indications and results.
AB  - Several types of lesions in adults can be differentiated. The author discusses
      his experience with 810 operated cases from 1975 to 1994.

PMID- 8567745
TI  - Neurotization procedures for brachial plexus injuries.
AB  - The author presents three methods for neurotization procedures. The methods were
      developed for different reconstructive purposes. Nerve transfer is often the only
      option to restore basic or total function.

PMID- 8567746
TI  - Restoration of hand function after brachial plexus injury.
AB  - Brachial plexus injuries effect hand function in different ways. Deficits may
      resemble those of a radial nerve palsy or those of an associated, high medioulnar
      paralysis. Analysis shows that active extension of the wrist is paramount in all
      procedures to gain quality results.

PMID- 8567747
TI  - Thoughts on the rehabilitation of patients with brachial plexus lesions.
AB  - This article concerns traction lesions of the brachial plexus in adults, focusing
      on management and recovery. Open wounds of the plexus are now treated surgically
      as soon as possible. The subsequent rehabilitation is the same as that for closed
      traction lesions of the brachial plexus in which significant recovery is
      expected.

PMID- 8567748
TI  - Cytokine induction of proliferation and expression of CDC2 and cyclin A in FDC-P1
      myeloid hematopoietic progenitor cells: regulation of ubiquitous and cell cycle
      dependent histone gene transcription factors.
AB  - To evaluate transcriptional mechanisms during cytokine induction of myeloid
      progenitor cell proliferation, we examined the expression and activity of
      transcription factors that control cell cycle-dependent histone genes in
      interleukin-3 (IL-3)-dependent FDC-P1 cells. Histone genes are transcriptionally
      upregulated in response to a series of cellular regulatory signals that mediate
      competency for cell cycle progression of the G1/S-phase transition. We therefore
      focused on factors that are functionally related to activity of the principal
      cell cycle regulatory element of the histone H4 promoter: CDC2, cyclin A, as well
      as RB- and IRF-related proteins. Comparisons were made with activities of
      ubiquitous transcription factors that influence a broad spectrum of promoters
      independent of proliferation or expression of tissue-specific phenotypic
      properties. Northern blot analysis indicates that cellular levels of cyclin A and
      CDC2 mRNAs increase when DNA synthesis and H4 gene expression are initiated,
      supporting involvement in cell cycle progression. Using gel-shift assays,
      incorporating factor-specific antibody and oligonucleotide competition controls,
      we define three sequential period following cytokine stimulation of FDC-P1 cells
      when selective upregulation of a subset of transcription factors is observed. In
      the initial period, the levels of SP1 and HiNF-P are moderately elevated; ATF, AP
      1, and HiNF-M/IRF-2 are maximal during the second period; while E2F and HiNF-D,
      which contain cyclin A as a component, predominate during the third period,
      coinciding with maximal H4 gene expression and DNA synthesis. Differential
      regulation of H4 gene transcription factors following growth stimulation is
      consistent with a principal role of histone gene promoter elements in integrating
      cues from multiple signaling pathways that control cell cycle induction and
      progression. Regulation of transcription factors controlling histone gene
      promoter activity within the context of a staged cascade of responsiveness to
      cyclins and other physiological mediators of proliferation in FDC-P1 cells
      provides a paradigm for experimentally addressing interdependent cell cycle and
      cell growth parameters that are operative in hematopoietic stem cells.

PMID- 8567749
TI  - Effect of cell cycle on the regulation of the cell surface and secreted forms of
      type I and type II human tumor necrosis factor receptors.
AB  - The cell cycle has been shown to regulate the biological effects of human tumor
      necrosis factor (TNF), but to what extent that regulation is due to the
      modulation of TNF receptors is not clear. In the present report we investigated
      the effect of the cell cycle on the expression of surface and soluble TNF
      receptors in human histiocytic lymphoma U-937. Exposure to hydroxyurea,
      thymidine, etoposide, bisbensimide, and demecolcine lead to accumulation of cells
      primarily in G1/S, S, S/G2/M, G2/M, and M stages of the cell cycle, respectively.
      While no significant change in TNF receptors occurred in cells arrested in G1/S
      or S/G2 stages, about a 50% decrease was observed in cells at M phase of the
      cycle. Scatchard analysis showed a reduction in receptor number rather than
      affinity. In contrast, cells arrested at S phase (thymidine) showed an 80%
      increase in receptor number. The decrease in the TNF receptors was not due to
      changes in cell size or protein synthesis. The increase in receptors, however,
      correlated with an increase in total protein synthesis (to 3.8-fold of the
      control levels). A proportional change was observed in the p60 and p80 forms of
      the TNF receptors. A decrease in the surface receptors in cells arrested in M
      phase correlated with an increase in the amount of soluble receptors. The
      cellular response to TNF increased to 8- and 2-fold in cells arrested in G1 and S
      phase, respectively; but cells at G2/M phase showed about 6-fold decrease in
      response. In conclusion, our results demonstrate that the cell cycle plays an
      important role in regulation of cell-surface and soluble TNF receptors and also
      in the modulation of cellular response.

PMID- 8567750
TI  - Cultured AIDS-related Kaposi's sarcoma (AIDS-KS) cells demonstrate impaired
      bioenergetic adaptation to oxidant challenge: implication for oxidant stress in
      AIDS-KS pathogenesis.
AB  - Despite its recognition as the most prevalent HIV associated cancer, speculation
      still abounds regarding the pathogenesis of AIDS-related Kaposi's sarcoma (AIDS
      KS). However, it has been established that both cytokines, e.g. IL-6, and HIV
      associated products, e.g., Tat, are integral in AIDS-KS cellular proliferation.
      Further, both experimental and clinical evidence is accumulating to link reactive
      oxygen intermediates (ROI) with both cytokine induction (primarily via nuclear
      factor-kappa B[NF-kappa B] dependent routes) as well as the subsequent cytokine,
      tumor necrosis factor alpha (TNF alpha) stimulation of HIV replication. Features
      of AIDS-KS patients, such as retention of phagocytes, presence of sustained
      immunostimulation, and a frequent history of KS lesions arising at traumatized
      sites, make oxidant stress a viable clinical factor in AIDS-KS development. Time
      course nucleotide profile analyses show that AIDS-KS cells have an inherent,
      statistically significant, biochemical deficit, even prior to oxidant stress, due
      to 1) a more glycolytic bioenergetic profile, resulting in lower levels of high
      energy phosphates (impairing capacity for glutathione [GSH] synthesis and DNA
      repair); 2) lower levels of NADPH (compromising the activities of GSSG reductase
      and peroxidase function of catalase); and 3) reduced levels of GSH (impeding both
      GSH peroxidase and GSH-S-transferases). Following exposure to physiologically
      relevant levels of H2O2, only the human microvascular endothelial cells (a
      putative AIDS-KS progenitor cell) responded with bioenergetic adaptations that
      reflected co-ordination of energy generating and cytoprotective pathways, e.g.,
      retention of the cellular energy charge, increased NAD+, and an accentuation of
      the ATP, NADPH, and total adenine nucleotide differences relative to AIDS-KS
      cells. Also, some of the AIDS-KS strains retained intracellular GSSG subsequent
      to oxidant challenge, inviting the formation of deleterious protein mixed
      disulfides. While the results of our study address some AIDS-KS issues, they also
      raise an etiological question, i.e., Does the inability to tolerate oxidant
      stress arise in conjunction with AIDS-KS neoplastic development, or is it pre
      existing in the population at risk? Regardless, use of antioxidant therapy (low
      risk/ potentially high benefit) in both the "at risk" population as well as in
      those individuals with active disease may prove a useful preventative and/or
      treatment modality.

PMID- 8567751
TI  - Expression of lysyl oxidase from cDNA constructs in mammalian cells: the
      propeptide region is not essential to the folding and secretion of the functional
      enzyme.
AB  - Rat aortic lysyl oxidase cDNA was expressed under a metallothionein promoter in
      Chinese hamster ovary cells using a dihydrofolate reductase selection marker. One
      methotrexate-resistant cell line, LOD-06, generated by transfecting with full
      length cDNA, yielded lysyl oxidase proteins consistent with the 50 kDa proenzyme
      and a 29 kDa mature catalyst. A second cell line, LOD32-2, was generated by
      transfection with a truncated cDNA lacking sequences which code for the bulk of
      the propeptide region. Both cell lines secreted apparently identical, 29 kDa
      forms of mature lysyl oxidase each of which catalyzed the deamination of human
      recombinant tropoelastin and alkylamines, consistent with the known specificity
      of lysyl oxidase. The secreted enzyme forms were inhibited by chemical inhibitors
      of lysyl oxidase activity, including beta-aminopropionitrile, phenylhydrazine,
      ethylenediamine, alpha, alpha'-dipyridyl, and diethyldithiocarbamate. Sensitivity
      to these agents is consistent with the presence of copper and carbonyl cofactors
      in the expressed enzymes, characteristic of lysyl oxidase from connective
      tissues. These results indicate the lack of essentiality of the deleted
      proprotein sequence for the proper folding, generation of catalytic function, and
      secretion of lysyl oxidase.

PMID- 8567752
TI  - Premature expression of cyclin B sensitizes human HT1080 cells to caffeine
      induced premature mitosis.
AB  - Eukaryotic cells do not normally initiate mitosis when DNA replication is
      blocked. This cell cycle checkpoint can be bypassed in some cells, however, by
      treatment with caffeine and certain other chemicals. Although S-phase arrested
      hamster cells undergo mitosis-specific events such as premature chromosome
      condensation (PCC) and nuclear envelope disassembly when exposed to caffeine,
      human cells show little response under the same conditions. To further
      investigate the molecular basis of this cell type specificity, a panel of
      hamster/human whole cell hybrids was created. The frequency of caffeine-induced
      PCC and the level of cyclin-B-associated H1 kinase activity in the various
      hybrids were directly correlated with the extent of cyclin B synthesis during S
      phase arrest. To determine whether expression of cyclin B alone could sensitize
      human cells to caffeine, cyclin B1 was transiently overexpressed in S-phase
      arrested HT1080 cells. The transfected cell population displayed a 5-fold
      increase in the frequency of caffeine-induced PCC when compared with normal
      HT1080 cells, roughly equivalent to the frequency of cells expressing exogenous
      epitope-tagged cyclin B1. In addition, immunofluorescent microscopy showed that
      individual cells overexpressing cyclin B1 during S phase arrest underwent PCC
      when exposed to caffeine. These results provide direct evidence that premature
      expression of cyclin B1 can make cells more vulnerable to chemically-induced
      uncoupling of mitosis from the completion of DNA replication.

PMID- 8567753
TI  - Endoplasmic reticulum protein Hsp47 binds specifically to the N-terminal globular
      domain of the amino-propeptide of the procollagen I alpha 1 (I)-chain.
AB  - Hsp47, an endoplasmic reticulum-resident heat shock protein in fibroblasts, has
      gelatin-binding properties. It had been hypothesized that it functions as a
      chaperone regulating procollagen chain folding and/or assembly, but the mechanism
      of the hsp47-procollagen I interaction was not clear. Hsp47 could bind to both
      denatured and native procollagen I. A series of competition studies were carried
      out in which various collagens and collagen domain peptides were incubated with
      35[S]-methionine-labeled murine 3T6 cell lysates prior to mixing with gelatin
      Sepharose 4B beads. The gelatin-bound proteins were collected and analyzed by gel
      electrophoresis and autoradiography. Collagenase digested procollagen I had the
      same effect as denatured intact procollagen, indicating that the propeptides were
      the major interaction sites. The addition of intact pro alpha 1(I)-N-propeptide
      at 25 micrograms/ml completely inhibited hsp47 binding to the gelatin-Sepharose.
      Even the pentapeptide VPTDE, residues 86-90 of the pro alpha 1(I)-N-propeptide,
      inhibits hsp47-gelatin binding. These data implicating the pro alpha 1(I)-N
      propeptide domain were confirmed by examination of polysome-associated pro alpha
      chains. The nascent pro alpha 1(I)-chains with intact N-propeptide regions could
      be precipitated by monoclonal hsp47 antibody 11D10, but could not be precipitated
      by monoclonal anti-pro alpha 1 (I)-N-propeptide antibody SP1.D8 unless
      dissociated from the hsp47. GST-fusion protein constructs of residues 23-108
      (NP1), 23-151 (NP2), and 23-178 (NP3) within the pro alpha 1 (I)- N-propeptide
      were coupled to Sepharose 4B and used as affinity beads for collection of hsp47
      from 3T6 cell lysates. NP1 and NP2 both showed strong specific binding for lysate
      hsp47. Finally, the interaction was studied in membrane-free in vitro
      cotranslation systems in which the complete pro alpha 1(I)- and pro alpha 2(I)
      chain RNAs were translated alone and in mixtures with each other and with hsp47
      RNA. There was no interaction evident between pro alpha 2(I)-chains and hsp47,
      whereas there was strong interaction between pro alpha 1(I)-chains and nascent
      hsp47. SP1.D8 could not precipitate pro alpha 1(I)-chains from the translation
      mix if nascent hsp47 was present. These data all suggest that if hsp47 has a
      "chaperone" role during procollagen chain processing and folding it performs this
      specific role via its preferential interaction with the pro alpha 1 (I) chain,
      and the pro alpha 1(I) amino-propeptide region in particular.

PMID- 8567754
TI  - Involvement of protein phosphatase-1 in cytoskeletal organization of cultured
      endothelial cells.
AB  - The phosphorylation and dephosphorylation of cytoskeletal proteins regulate the
      shape of eukaryotic cells. To elucidate the role of serine/threonine protein
      phosphatases (PP) in this process, we studied the effects of calyculin A (CLA), a
      potent and specific inhibitor of protein phosphatases 1 (PP-1) and 2A (PP-2A) on
      the cytoskeletal structure of cultured human umbilical vein endothelial cells
      (HUVECs). The addition of CLA (5 min) caused marked alterations in cell
      morphology, such as cell constriction and bleb formation. Microtubules and F
      actin were reorganized, becoming markedly condensed around the nucleus. Although
      the fluorescence intensity of phosphoamino acids was not significantly different
      according to immunocytochemistry between cells with and without CLA, polypeptides
      of 135, 140, 158, and 175 kDa were specifically phosphorylated on serine and/or
      threonine residues. There was no significant effect on tyrosine residues. The
      effects of CLA on cytoskeletal changes and protein phosphorylation were almost
      completely inhibited by the non-selective kinase inhibitor, K-252a. The effect of
      CLA on cell morphology was at least 100 times more potent than that of okadaic
      acid, consistent with the inhibitory potency against PP-1. The catalytic subunit
      of PP-1 was also identified in HUVECs by Western blotting with its monoclonal
      antibody antibody. These results suggest that PP-1 is closely involved in
      sustaining the normal structure of the cytoskeleton.

PMID- 8567755
TI  - Glucocorticoids coordinately regulate type I collagen pro alpha 1 promoter
      activity through both the glucocorticoid and transforming growth factor beta
      response elements: a novel mechanism of glucocorticoid regulation of eukaryotic
      genes.
AB  - Glucocorticoids have previously have shown to decrease Type I collagen synthesis
      in vivo and in fibroblast cell culture. Several studies have demonstrated that
      glucocorticoids decrease Type I procollagen gene expression. These latter studies
      have included uridine incorporation into pro alpha 1 (I) and pro alpha 2 (I)
      mRNAs and nuclear run-off experiments. Using the ColCat 3.6 plasmid, which
      contains part of the 5' flanking region of the pro alpha 1 (I) collagen gene and
      the reporter gene, chloramphenicol acetyltransferase, the present studies
      demonstrate by stable transfection of fetal rat skin fibroblasts that
      dexamethasone down regulates the promoter activity of the pro alpha 1 (I)
      collagen gene. The glucocorticoid-mediated down-regulation of procollagen gene
      expression was demonstrated using the ColCat 3.6, 2.4, 1.7, or 0.9 plasmid. In
      addition, competitive oligonucleotide transfection experiments and site specific
      mutation of the glucocorticoid response element (GRE) in the whole ColCat 3.6
      plasmid did not eliminate the effect. The possibility existed that another cis
      element in the 5' flanking region of the pro alpha 1 (I) collagen gene was also
      required for the collagen glucocorticoid-mediated down-regulation of procollagen
      gene expression, since TGF-beta has been shown to stimulate in a decrease of
      transforming growth factor-beta (TGF-beta) secretion into the media. Gel mobility
      studies demonstrated that glucocorticoid treatment of rat skin fibroblasts
      decreased glucocorticoid receptor binding to the GRE and TGF-beta activator
      protein to the TGF-beta element which were brought back to control values by
      coordinate exogenous TGF-beta treatment. Thus the interaction of these TGF-beta
      molecules with cellular membrane receptors and subsequent transduction is
      dramatically decreased resulting in less signals to regulate collagen gene
      expression. These data indicate that glucocorticoids coordinately regulate
      procollagen gene expression through both the GRE and TGF-beta elements.
      Depression of procollagen gene expression by glucocorticoids through the TGF-beta
      element is mediated by decreased TGF-beta secretion, possibly involving a
      secondary effect on regulatory protein(s) encoded by noncollagenous protein
      gene(s). The present studies provide the basis for a novel mechanism of
      glucocorticoid-mediator regulation of eukaryotic genes containing the TGF-beta
      element.

PMID- 8567756
TI  - Arrest at the G2/M transition of the cell cycle by protein-tyrosine phosphatase
      inhibition: studies on a neuronal and a glial cell line.
AB  - The addition of the peroxovanadium (pV) derivatives potassium bisperoxo(1,10
      phenanthroline)oxovanadate(v) (bpV[phen]) or potassium bisperoxo(pyridine-2
      carboxylato) oxovanadate(v) (bpV[pic]), both of which are potent inhibitors of
      protein tyrosine phosphatases (PTPs) [Posner et al. (1994): J Biol Chem 269:4596
      4604], to the culture medium of neuroblastoma NB 41 and glioma C6 cells resulted
      in a marked decrease in their proliferation rates and a progressive accumulation
      at the G2/M transition of the cell cycle. The effect was dependent on dose, cell
      type, and a pV compound employed. Mean values of the RNA-to-DNA and RNA-to
      protein ratios in NB cells treated for 48 h with increased doses of bpV[phen]
      showed that general synthetic functions were not altered, nor did we observe
      oxidative damage to DNA using a sensitive DNA-nick detection assay. No changes in
      the expression and localization of vimentin, a component of the intermediate
      filament cytoskeleton, were observed by indirect immunofluorescence, showing that
      treatment did not disturb the cytoskeleton network. Measurements of BrdU
      incorporation into newly synthesized DNA showed that cells treated were not
      totally arrested. Furthermore, cells arrested G2/M were able to reenter the cycle
      rapidly after the release of inhibition. This progressive accumulation of G2/M
      coincided with the detection of tyrosine-phosphorylated p34cdc2 and a dramatic
      reduction in its kinase activity toward histone H1 by 48 h of culture. Both
      compounds were equally potent in inhibiting the catalytic activity of a yeast and
      the structurally distant mouse cdc25B in vitro, suggesting that augmented
      tyrosine phosphorylation of p34cdc2 derived from the in vivo inhibition of cdc25.
      Their equal in vitro potency contrasted with the considerably greater potency of
      bpV[phen] in vivo, in vivo suggesting that factors regulating the intracellular
      access of these compounds to cdc25 might be critical in determining in vivo
      specificity. In conclusion the final consequence of long-term exposure to potent
      and structurally defined PTP inhibitors on two highly proliferative nerve cell
      lines is to restrict cell growth. The corresponding hyperphosphorylation and
      reduced activity of p34cdc2 likely reflects the unusual sensitivity of cdc25 as
      an in vivo target for peroxovanadium compounds.

PMID- 8567757
TI  - The RB2/p130 gene product is a nuclear protein whose phosphorylation is cell
      cycle regulated.
AB  - The Rb2/p130 protein has been shown to have a high sequence homology with the
      retinoblastoma gene product (pRb), one of the most well-characterized tumor
      suppressor genes, and with pRB-related p107, especially in their conserved pocket
      domains, which display a primary role in the function of these proteins. In this
      study, we report on the biochemical and immunocytochemical characterization of
      the Rb2/p130 protein, using a polyclonal antibody developed against its "spacer"
      region included in the pocket domain of the whole protein. We show that pRb2/p130
      is a phosphoprotein located at the nuclear level and that its phosphorylation
      pathway can be dramatically reduced by phosphatase treatment. Moreover pRb2/p130
      with p107, is one of the major targets of the E1A viral oncoprotein-associated
      kinase activity, showing a phosphorylation pattern which is modulated during the
      cell cycle, reaching a peak of activation at the onset of S-phase.

PMID- 8567758
TI  - Intracytoplasmic sperm injection--what kind of reproduction is being assisted?

PMID- 8567759
TI  - Intracytoplasmic sperm injection (ICSI): potential genetic concerns.

PMID- 8567760
TI  - Intracytoplasmic sperm injection--is there a need for an animal model, especially
      in assessing the genetic risks involved?

PMID- 8567761
TI  - Is an animal model needed for intracytoplasmic sperm injection (ICSI) and other
      assisted reproduction technologies?

PMID- 8567762
TI  - Intracytoplasmic sperm injection three years after the birth of the first ICSI
      child.

PMID- 8567763
TI  - Follicular phase length, cycle day of conception and sex ratio of offspring.

PMID- 8567764
TI  - Genetic control of the secondary sex ratio.

PMID- 8567765
TI  - A prospective, randomized, assessor-blind, multicentre study comparing
      recombinant and urinary follicle stimulating hormone (Puregon versus Metrodin) in
      in-vitro fertilization.
AB  - Urinary follicle stimulating hormone (FSH) is being used for the treatment of
      human infertility. Recently, FSH manufactured by means of recombinant DNA
      technology with a much higher purity (> 99%) has become available. A prospective,
      randomized, assessor-blind, multicentre (n = 18) study was conducted in infertile
      women undergoing in-vitro fertilization comparing recombinant FSH (Org 32489,
      Puregon) and urinary FSH (Metrodin). Eligible subjects were randomized
      (recombinant versus urinary FSH = 3:2) and pretreated with buserelin for
      pituitary suppression. FSH was given until three or more follicles with a
      diameter of at least 17 mm were seen. After oocyte retrieval, fertilization
      routines were applied according to local procedures. No more than three embryos
      were replaced. In all, 585 subjects received recombinant FSH and 396 urinary FSH.
      Significantly more oocytes were retrieved after recombinant FSH treatment (mean
      adjusted for centre 10.84 versus 8.95, P < 0.0001). Ongoing pregnancy rates per
      attempt and transfer in the recombinant FSH group were 22.17 and 25.97%
      respectively, and in the urinary FSH group, 18.22 and 22.02% respectively (not
      significant). Ongoing pregnancy rates including pregnancies resulting from frozen
      thawed embryo cycles were 25.7% for recombinant and 20.4% for urinary FSH (P =
      0.05). Compared to urinary FSH, the total dose of FSH was significantly lower
      with recombinant FSH (2138 versus 2385 IU, P < 0.0001) in a significantly shorter
      treatment period (10.7 versus 11.3 days, P < 0.0001). No clinically relevant
      differences between recombinant and urinary FSH were seen with respect to safety
      variables. It is concluded that recombinant FSH (Puregon) is more effective than
      urinary FSH in inducing multifollicular development and achieving an ongoing
      pregnancy.

PMID- 8567766
TI  - Gonadotrophin-releasing hormone agonist compared with human chorionic
      gonadotrophin for ovulation induction after clomiphene citrate treatment.
AB  - The objective of this study was to compare hormonal response, luteal phase
      adequacy and pregnancy and abortion rates in patients randomized to receive human
      chorionic gonadotrophin (HCG) or gonadotrophin-releasing hormone agonist (GnRHa)
      during ovulation cycles stimulated by clomiphene citrate. Anovulatory patients
      received either one s.c. dose of tryptorelin (0.1 mg; n = 104) or one i.m. dose
      of HCG (10,000 IU; n = 106) after clomiphene citrate stimulation had induced
      enlarged ovarian follicles (> 17 mm in diameter). A short-lived, transitory
      increase in serum luteinizing hormone (98 +/- 9 IU/l) and follicle-stimulating
      hormone (30 +/- 5 IU/l) concentrations was measured at 12 h following the
      injection of GnRHa, and these concentrations returned to baseline levels by 36 h
      post-injection. Midluteal progesterone concentrations were similar in both groups
      (> 10 ng/ml), and the mean luteal phase duration was also not significantly
      different (13 days). There were no significant differences in the mean number of
      pregnancies (12.0 versus 12.6% per cycle) and the abortion rate (18.2 versus
      12.5%) between the GnRHa- and HCG-treated groups respectively. There were no
      complications related to treatment in either group. The results show that a
      relatively low dose of GnRHa can be used in place of HCG to induce ovulation in
      clomiphene citrate-treated patients.

PMID- 8567767
TI  - The prognostic value of basal luteinizing hormone:follicle-stimulating hormone
      ratio in the treatment of patients with polycystic ovarian syndrome by assisted
      reproduction techniques.
AB  - One of the main endocrinological disturbances in patients with polycystic ovarian
      syndrome (PCOS) is the increased baseline concentrations of luteinizing hormone
      (LH) and consequently a high LH:follicle-stimulating hormone (FSH) ratio. The aim
      of this study was to assess the relationship between the baseline LH:FSH ratio
      with the stimulation response and the miscarriage risk in PCOS women stimulated
      for assisted reproduction techniques (ART) with and without gonadotrophin
      releasing hormone analogue (GnRHa). Two groups of PCOS patients were analysed
      retrospectively. Group A (n = 20, 20 cycles) consisted of women stimulated with
      human menopausal gonadotrophin (HMG), and group B (n = 128, 162 cycles) comprised
      women stimulated with buserelin-long/HMG. LH and FSH concentrations were measured
      during the early follicular phase (days 4-6) in a preceding spontaneous or
      progestin-induced cycle. The following parameters were assessed: number of
      follicles developed, number of oocytes obtained and percentage of mature oocytes,
      as well as number of abortions and live births. In group A, the baseline LH:FSH
      ratio was correlated inversely with the number of follicles developed (P < 0.05),
      the number of oocytes obtained (P < 0.05) and the percentage of mature oocytes (P
      < 0.05). In group B, no correlation was found between the LH:FSH ratio and the
      number of follicles and oocytes, because their numbers were relatively constant
      irrespective of the baseline LH:FSH ratio, but a significant inverse correlation
      was noted with the percentage of mature oocytes (P < 0.001). However, a
      comparison of the slopes of the curve indicated a better correlation between the
      LH:FSH ratio and the percentage of mature oocytes in group A than in group B (P <
      0.05). These findings were also confirmed when patients were subdivided according
      to the LH:FSH ratio (< 3 or > or = 3). Furthermore, in women who miscarried, the
      mean LH:FSH ratio was significantly higher than in women having a live birth. In
      conclusion, in PCOS patients stimulated with HMG, a high basal LH:FSH ratio
      appears to have an adverse effect on the number of follicles and oocytes, as well
      as on oocyte maturity. On the other hand, the administration of GnRHa in the long
      protocol seems to reverse this detrimental effect on follicle and oocyte
      development. Furthermore, a higher LH:FSH ratio seems to predict a greater
      possibility for miscarriage, despite the use of GnRHa.

PMID- 8567768
TI  - Adjuvant growth hormone for induction of ovulation with gonadotrophin-releasing
      hormone agonist and gonadotrophins in polycystic ovary syndrome: a randomized,
      double-blind, placebo controlled trial.
AB  - The objective of this study was to explore the effect of cotreatment with
      recombinant human growth hormone (GH), gonadotrophin-releasing hormone agonist
      (GnRHa) and human menopausal gonadotrophin (HMG) for induction of ovulation in
      women with clomiphene resistant polycystic ovary syndrome (PCOS). It was designed
      as a randomized, double-blind, placebo controlled trial in which 30 women with
      anovulation associated with PCOS who were resistant to clomiphene all received
      DTRP6-LHRH (Decapeptyl microcapsules, 3.75 mg, i.m.) and, 2 weeks later, HMG in a
      standard, conventional, individually adjusted dose regimen until human chorionic
      gonadotrophin (HCG) and then luteal phase support could be given. From day 1 of
      HMG therapy, patients were randomized to receive either human GH (Norditropin, 12
      IU/day, i.m., for 7 days) or placebo. The number of ampoules, duration of
      treatment and daily effective dose of HMG required to achieve ovulation, serum
      oestradiol concentrations and number of follicles induced, ovulation and
      pregnancy rates, serum insulin and insulin-like growth factor-I (IGF-I)
      concentrations were measured. There were no significant differences between
      growth hormone and placebo groups in any of the outcomes measured, other than a
      growth hormone induced increase in serum insulin and IGF-I levels. We conclude
      that although GH kinetics are abnormal and GH pituitary reserves generally low in
      women with PCOS, adjuvant GH treatment to GnRHa/HMG does not influence follicular
      development or sensitivity in response to gonadotrophins and that it does not
      seem likely to be of any potential clinical benefit for the treatment of PCOS.

PMID- 8567769
TI  - Time-dependent effects of transforming growth factor alpha on aromatase activity
      in human granulosa cells.
AB  - Transforming growth factor alpha (TGF alpha) is implicated as a paracrine growth
      factor in the regulation of human granulosa cell function. To investigate this
      further, we have examined the actions of TGF alpha on the basal and follicle
      stimulating hormone (FSH)-stimulated aromatase activity of human granulosa cells
      to determine how this growth factor influences oestrogen biosynthesis in the
      follicle. Granulosa cells from women having in-vitro fertilization during
      untreated or gonadotrophin-stimulated cycles were cultured for 1-6 days in the
      presence or absence of FSH or TGF alpha at a range of doses. Aromatase activity,
      expressed as oestradiol production, was determined after culture during a 3 h
      test period. After 2 days, TGF alpha (1-300 ng/ml) decreased basal and FSH
      stimulated aromatase activity in a dose-dependent manner (ED50 = 3 ng/ml). In
      contrast, after 4 days, TGF alpha enhanced both basal and FSH-stimulated
      aromatase activity. Repeated experiments revealed a consistent pattern of
      inhibition on day 2, which was more marked in the presence of FSH (reduction by
      30.6 +/- 9.1%, mean +/- SEM; n = 14; P < 0.01), and stimulation on day 4 in both
      the absence (increased by 61.4 +/- 20.6%, mean +/- SEM; n = 6; P < 0.05) and
      presence of FSH (increased by 36.0 +/- 15.2%, mean +/- SEM; n = 8; P < 0.05). The
      results provide further evidence that TGF alpha is a paracrine factor in the
      control of oestrogen biosynthesis, but the actions can be either inhibitory or
      stimulatory depending on the duration of exposure.

PMID- 8567770
TI  - Autoimmune disorders: another possible cause for in-vitro fertilization and
      embryo transfer failure.
AB  - This study was undertaken to investigate the role of autoantibodies in
      association with in-vitro fertilization (IVF) and embryo transfer failure.
      Anticardiolipin, lupus anticoagulant, anti-deoxyribonucleic acid and antinuclear
      antibody, rheumatoid factor and antithyroid antibody concentrations were
      measured. The study group comprised 50 IVF patients with three or more previously
      failed cycles after embryo transfer. The control group comprised 80 computer
      matched women: 40 who had conceived and delivered following three or less IVF and
      embryo transfer cycles, and 40 who were healthy nulligravidas. The incidence of
      autoantibodies in the study group was 22.0%, compared with 2.5% in the IVF
      control group (P < 0.05) and 7.5% in the nulligravida group (P < 0.05). In the
      study group, no statistical difference was found between the patients with
      unexplained infertility and those with mechanical infertility (23.0 and 20.8%
      respectively). The high occurrence of autoantibodies found in patients who failed
      at least three IVF and embryo transfer cycles could imply that these
      autoantibodies may be one of the possible causes of IVF failure in either
      mechanical or unexplained infertility. Further investigations are required to
      indicate the autoantibody profile as part of the work-up after three or more
      failed IVF and embryo transfer attempts.

PMID- 8567771
TI  - Autoantibodies and antisperm antibodies in sera and follicular fluids of
      infertile patients; relation to reproductive outcome after in-vitro
      fertilization.
AB  - Immune reactions have effects at various concentrations in the reproductive
      process and autoantibodies may have an impact on fertility and the outcome of
      assisted conception. We measured the prevalence of and relation between
      antibodies to smooth muscle, nuclear, phospholipid and sperm antigens, and
      concentrations of immunoglobulins G, M and A and complement components C3 and C4,
      in the sera and follicular fluids of women with unexplained infertility (n = 30),
      endometriosis (n = 20), tubal infertility (n = 50) and the sera of 20 normal non
      pregnant women. We assessed fertilization and successful pregnancy rates in
      relation to antibody status of infertile women after in vitro fertilization. All
      antibodies had a higher prevalence in infertile women compared with controls and
      this was significant for smooth muscle antibody in endometriosis (P < 0.05);
      anticardiolipin antibody in tubal infertility (P < 0.05); and antisperm antibody
      in all types of infertility (P < 0.001). There was no relation between presence
      of specific antibodies in serum or between serum and follicular fluids. Total
      biochemical pregnancy rate was higher with endometriosis (P = 0.05) but clinical
      pregnancy and live birth rates did not differ between groups or in relation to
      antibody status. Significant differences in immunoglobulin and complement
      components occurred in women with and without successful biochemical pregnancy.

PMID- 8567772
TI  - Chromosomes of oocytes failing in-vitro fertilization.
AB  - Of 263 oocytes that failed to fertilize after in-vitro fertilization and were
      sent for cytogenetic investigation, 179 (68.1%) were analysable. More than 72.0%
      were normal metaphase II haploids (23,X). Hyperhaploidy, hypohaploidy and complex
      cases made up a total aneuploidy rate of 12.3%, while 10.1% were diploid. In
      addition, there were five oocytes with structural aberrations and eight yielded
      chromatids only. The total chromosome aberration rate was 29.1%. No significant
      difference was found between the aneuploidy rate and maternal age. Here we
      present photographic evidence of oocytes with extra whole chromosomes and extra
      single chromatids. We suggest that both predivision and nondisjunction contribute
      to the formation of trisomy in man.

PMID- 8567773
TI  - Effect of uterine leiomyomata on the results of in-vitro fertilization treatment.
AB  - The effect of uterine leiomyoma on infertility is subject to controversy. Two
      main mechanisms associating leiomyomata and infertility have been suggested: the
      obstruction of gamete transport and impaired implantation. In-vitro fertilization
      (IVF) is a unique setting for examining the effect of leiomyomata on the
      implantation rate. This study was designed to determine the impact of uterine
      leiomyomata on the results of IVF. In a retrospective analysis of IVF cycles, 46
      women with documented uterine leiomyoma were compared with a control group with
      mechanical infertility. The implantation rate and pregnancy outcome in relation
      to the leiomyoma were observed. Implantation (22.1%/transfer, 6.8%/embryo) and
      abortion rates (36%) in the study group were similar to the results in the
      control group with pure mechanical factor. An analysis of IVF results according
      to the hysteroscopic pretreatment findings revealed that impaired implantation is
      associated with leiomyoma only where uterine intracavitary abnormalities co
      exist. We conclude that implantation rate and pregnancy outcome are impaired in
      women with uterine leiomyomata only when they cause deformation of the uterine
      cavity. In patients with leiomyomata associated with an abnormal uterine cavity,
      surgical treatment should be considered prior to IVF because of the reduced
      implantation rate.

PMID- 8567774
TI  - Reduced endothelial cell migratory signal production by endometrial explants from
      women using Norplant contraception.
AB  - Bleeding problems can be one of the major reasons for women to discontinue the
      use of hormonal contraceptives. Causes of endometrial bleeding can include
      disturbances in endometrial regeneration and angiogenesis. Endothelial cells
      migrate and proliferate rapidly as part of the angiogenic process under the
      influence of appropriate stimuli. The aim of this study is to investigate the
      production of endothelial cell migratory signals by endometrial explants from
      women receiving Norplant and to compare it to that of those with a normal
      menstrual cycle. The subjects were selected from Norplant users with an exposure
      of 3-9 months. The endothelial cell migratory signal production was assayed using
      the Folkman method (1989), modified by Rogers (1992). Blood serum concentrations
      of oestradiol, progesterone and sex hormone binding globulin were monitored for 2
      weeks prior to endometrial biopsy. Endothelial cell migration toward endometrial
      explants of 30 women as control and 46 Norplant acceptors was assayed. The
      results showed that endothelial cell migratory activity toward endometrial
      explants from the control group was significantly higher than toward those from
      Norplant acceptors (z = 3.89, P < 0.001). There were no differences between
      endometrial endothelial cell migratory activities in Norplant acceptors with
      bleeding or without bleeding problems.

PMID- 8567776
TI  - The effect of seminal plasma on human sperm-zona pellucida binding.
AB  - The aim of this study was to determine the effect of different concentrations of
      seminal plasma (SP) in insemination medium on human sperm-zona pellucida (ZP)
      binding. The effects of fresh SP [50% (n = 10) and 1% (n = 9)], frozen-thawed
      versus fresh SP [5% (n = 10)] and frozen-thawed SP [5% (n = 10) and 1% (n = 9)]
      on sperm-ZP binding were examined using hemizona assays. The validity of the
      hemizona assay as performed in this study was also examined. Relative sperm
      binding percentages were determined for respective hemizonae, and the hemizona
      index was calculated for each experimental group and compared statistically. The
      50% native SP inhibited sperm-ZP binding by approximately 70% (P = 0.0051), while
      1% native SP enhanced sperm-ZP binding by approximately 350% (P = 0.0051).
      Significantly more spermatozoa (mean +/- SD, 172.00 +/- 54.12) bound to zonae in
      the presence of 5% frozen-thawed SP than with 5% SP that had not been frozen
      (mean +/- SD, 127.00 +/- 69.18; P = 0.0431). The 1 and 5% frozen-thawed SP
      stimulated sperm-ZP binding by approximately 400 and approximately 250%
      respectively (P = 0.0077 and 0.0051 respectively). It is concluded that SP
      concentrations found in insemination media during assisted reproductive
      techniques do not inhibit but in fact enhance sperm-ZP binding.

PMID- 8567775
TI  - Immunolocalization of endothelin and neutral endopeptidase in the endometrium of
      users of subdermally implanted levonorgestrel (Norplant).
AB  - Subdermally implanted slow-release levonorgestrel (Norplant), a widely used
      effective contraceptive, has a high rate of discontinuation due to unacceptable
      menstrual bleeding disturbances. Endothelin (ET), a potent vasoconstrictor,
      varies across the menstrual cycle in normal endometrium. It has been proposed
      that ET has a potential paracrine role in the regulation of uterine blood flow.
      Neutral endopeptidase (NEP), a membrane-bound ecto-enzyme, can inactivate ET and
      is localized principally in endometrial stroma. We have compared the immuno
      localization of ET and NEP in endometrial biopsies from Indonesian women using
      Norplant with normal controls. Differences were observed in the glandular and
      luminal epithelium of Norplant-treated subjects, where ET immunostaining was low
      while NEP immunoreactivity was increased. The latter may represent a local
      increase in enzyme activity, potentially explaining the reduced ET
      immunoreactivity. There was no correlation of ET immuno-reactivity with the
      duration of implant use or total number of bleeding days. The marked differences
      in the ET immunostaining pattern in Norplant users, with their increased risk of
      abnormal uterine bleeding, suggest that ET may be important in controlling
      menstrual bleeding. Whether endometrial epithelial cell ET has a role as a
      mitogen in endometrial repair and regeneration, or as a vasoconstrictor important
      in the cessation of bleeding following menstruation, remains to be determined.

PMID- 8567777
TI  - Testicular needle biopsy, open biopsy, epididymal aspiration and intracytoplasmic
      sperm injection in obstructive azoospermia.
AB  - Testicular or epididymal spermatozoa were obtained for in-vitro fertilization and
      intracytoplasmic sperm injection (ICSI) in 27 cycles out of 33 (in six men the
      azoospermia proved to have testicular causes). Testicular needle biopsy carried
      out in addition to surgical open biopsy proved to be an effective method to
      obtain spermatozoa for ICSI from patients with obstructive azoospermia. Thus it
      might be possible to replace scrotal operations by simple needle biopsies.
      Embryos resulting from ICSI with testicular spermatozoa were used in 19 transfers
      that resulted in six pregnancies. One pregnancy resulted from six embryo
      transfers from ICSI after microsurgical-epididymal sperm aspiration (MESA). The
      normal fertilization rates with testicular (37.3%) and MESA spermatozoa (53.7%)
      did not differ significantly from each other, but with testicular spermatozoa the
      rate was significantly lower than that obtained with ejaculated spermatozoa and
      ICSI (59.7%) in the matched couples. The abnormal fertilization of oocytes with
      one pronucleus was significantly higher with testicular spermatozoa than with
      ejaculated spermatozoa in the control couples.

PMID- 8567778
TI  - Does treatment with testosterone undecanoate improve the in-vitro fertilizing
      capacity of spermatozoa in patients with idiopathic testicular failure? (results
      of a double blind study).
AB  - Seventy-seven couples in whom conventional in-vitro fertilization (IVF) had
      remained unsuccessful because of low fertilization rate and abnormal sperm
      characteristics were given either testosterone undecanoate 120 mg/day, or placebo
      during 3 months, after which a new IVF treatment was applied under identical
      technical conditions. There were no significant changes in sperm characteristics
      among the treated and placebo couples and the fertilization rate showed a similar
      increase after treatment in both groups. No significant difference in pregnancies
      occurred, with 32% pregnancies in the placebo controls and 17% among couples
      treated with testosterone undecanoate. It is concluded that testosterone
      undecanoate intake does not improve sperm characteristics, or the in-vitro
      fertilizing potential, or pregnancy rate over those observed in the placebo
      controls in cases with primary idiopathic testicular failure.

PMID- 8567779
TI  - Hyperactivation may assist human spermatozoa to detach from intimate association
      with the endosalpinx.
AB  - The behaviour of human spermatozoa was observed during incubation with epithelial
      cells isolated from the isthmic and ampullary sections of human uterine
      (Fallopian) tubes. During incubation, spermatozoa were observed to bind to the
      epithelial cells of the tube (the endosalpinx), and individual spermatozoa
      attached and detached at intervals. The kinematic characteristics of spermatozoa
      during these behaviour patterns were determined. The results showed that detached
      spermatozoa typically had an increased curvilinear velocity and amplitude of
      lateral head displacement, accompanied by a decrease in their linearity.
      Significantly (P < 0.01) more of the detaching spermatozoa were hyperactivated
      than were spermatozoa prior to attachment for both isthmic (35.3 +/- 5.5 versus
      4.0 +/- 3.3%; mean +/- SEM) and ampullary (26.0 +/- 7.0 versus 2.0 +/- 1.4%)
      regions. Incubation with epithelial cells from either region produced no
      differences in any category of sperm behaviour. Furthermore, there was no
      significant difference between regions in the amount of time spermatozoa spent
      bound (33.6 +/- 12.9 and 20.6 +/- 3.0 s for isthmic and ampullary tissue
      respectively). These results support the hypothesis that hyperactivation may
      assist spermatozoa in breaking connections with epithelial cells.

PMID- 8567780
TI  - Six year follow-up of cryopreserved human embryos.
AB  - In 1987, we became aware of the importance of remaining in contact with couples
      whose embryos had been cryopreserved for > 1 year. As a result, a questionnaire
      was designed to follow the fate of these embryos. Of 407 couples with
      cryopreserved embryos, 262 couples opted to use them within 1 year with the
      intention of fulfilling a parental plan. The remaining 145 couples were
      questioned by six successive questionnaires sent out between 1987 and 1992. By
      the end of the study, 336 of the 407 couples (82.5%) had chosen to utilize their
      embryos in a parental plan. In most cases, the maximum delay of response (5 years
      according to the Council of State) was respected. The remaining 71 couples
      (17.5%) either abandoned the parental plan or had not given any information by
      the end of the study. Initially, anonymous donation to another couple was chosen
      in preference to destroying the surplus embryos (32 versus 18 couples, P < 0.05).
      Latterly, however, these differences have balanced out (24 versus 28, not
      significant). Only those couples who initially opted to donate embryos to another
      couple changed their attitude in later years. In the long run, 62 couples decided
      not to pursue their parental plan; of these, 24 couples chose to make a gift to
      another couple, 28 couples opted for destruction, and 10 chose to make a gift to
      research. Nine couples (out of 71) declined to make a decision, but they had all
      achieved a pregnancy during an in-vitro fertilization (IVF) attempt. Three of
      these were lost to follow-up, i.e. 0.7% of all couples benefiting from the
      freezing technique.

PMID- 8567781
TI  - Morphological and cytogenetic observations of unfertilized human oocytes and
      abnormal embryos obtained after ovarian stimulation with pure follicle
      stimulating hormone following pituitary desensitization.
AB  - Morphological and cytological observations of 189 unfertilized oocytes and 40
      abnormal embryos obtained from 32 patients in a routine in-vitro fertilization
      programme were performed. Both the oocytes and the embryos were mounted whole to
      preserve the original topology of all the structural elements. With the applied
      protocol of ovarian stimulation associating pituitary desensitization and
      follicle stimulating hormone stimulation, a high degree of immaturity of the
      unfertilized eggs was observed in comparison with previous reports. This
      immaturity was deduced from the higher incidence of unfertilized eggs arrested at
      the germinal vesicle or metaphase I stage, as well as metaphase II oocytes with
      multiple metaphase plates. Nine triploid and four tetraploid embryos were
      analysed: except for one tetraploid embryo, all the polyploid embryos cleaved.
      The percentages of mononucleated blastomeres in these polyploid embryos were 57
      and 27% respectively. We also analysed 21 cleaving diploid embryos which
      exhibited a high degree of fragmentation. No more than 40% of the blastomeres
      contained a single nucleus. Moreover, in only one of the 21 diploid embryos could
      all the blastomeres be considered normal.

PMID- 8567782
TI  - Aetiology of failed and abnormal fertilization after intracytoplasmic sperm
      injection.
AB  - The aim of this study was to determine why oocytes remain unfertilized or develop
      three pronuclei after intracytoplasmic sperm injection (ICSI). Unfertilized and
      abnormally fertilized oocytes were fixed in glutaraldehyde, stained with Hoechst
      33342 and examined by fluorescence microscopy to identify oocyte, sperm and polar
      body DNA. One-pronuclear oocytes were considered to be unfertilized. A total of
      285 unfertilized oocytes were examined (104 ICSI cycles). Overall, 83% of these
      oocytes were not activated (still at metaphase II) while 17% had activated and
      formed a single (female) pronucleus. About 66% of the unfertilized, metaphase II
      oocytes contained a swollen sperm head, indicating that the oocyte was correctly
      injected but had failed to activate and complete the second meiotic division.
      Premature chromosome condensation of the sperm DNA was evident in 6% of these
      metaphase II oocytes (4% of the unfertilized oocytes). The swollen sperm head was
      located among the oocyte chromosomes in 5% of the metaphase II oocytes. Other
      causes of failed fertilization in the metaphase II oocytes were the failure of
      sperm head decondensation (11%) and ejection of the spermatozoon from the oocyte
      (23%). A similar pattern was observed in one-pronuclear oocytes (52%, swollen
      sperm head; 28%, intact, undecondensed sperm head; 20%, ejection of the
      spermatozoon), which indicates that asynchronous pronuclear development does not
      explain the presence of one-pronuclear oocytes. A total of 41 three-pronuclear
      oocytes were examined and all had a single polar body, which indicates that the
      retention of the second polar body leads to the formation of the third
      pronucleus. In conclusion, this study demonstrates that: (i) the major cause of
      fertilization failure after ICSI is failure of oocyte activation; (ii) ejection
      of the spermatozoon into the perivitelline space is not a major cause of
      fertilization failure; and (iii) sperm head decondensation and oocyte activation
      after ICSI can occur independently.

PMID- 8567783
TI  - Analysis of 76 total fertilization failure cycles out of 2732 intracytoplasmic
      sperm injection cycles.
AB  - From October 1992 to December 1994, 2732 cycles of treatment by intracytoplasmic
      sperm injection (ICSI) were carried out in couples mainly with severe male-factor
      infertility. The overall fertilization rate in these 2732 cycles was 71% of
      intact oocytes. However, in 76 (72 couples) of these cycles, none of the injected
      oocytes became fertilized, so the total fertilization failure rate was 3%
      (76/2732 cycles). Details of these 76 cycles were analysed. The results show that
      total fertilization failure after ICSI may be explained by different factors
      related to (i) semen characteristics (only immotile or round-headed spermatozoa
      for ICSI) or (ii) the oocytes (number, abnormal morphology, damage after ICSI).
      Of 26 couples, 22 achieved fertilization in their subsequent ICSI cycles. In
      conclusion, total fertilization failure after ICSI for the treatment of severe
      male-factor infertility was mainly caused by the poor viability of the
      spermatozoa used for injection; it was also associated with a low number and poor
      quality of oocytes. Repeated ICSI treatment may be useful or necessary in couples
      with total fertilization failure.

PMID- 8567784
TI  - Intracytoplasmic sperm injection and embryo development of human oocytes
      cryopreserved using 1,2-propanediol.
AB  - This study reports the subsequent embryo development of cryopreserved mature
      human oocytes following insemination or intracytoplasmic sperm injection (ICSI).
      Metaphase II oocytes were cryopreserved using a slow freezing-rapid thawing
      procedure employing the cryoprotectant 1,2-propanediol. The study was conducted
      at two centres. The normal insemination of cryopreserved oocytes was undertaken
      in one centre, and ICSI of cryopreserved oocytes in the other. Both methods
      resulted in a 50% normal fertilization rate. A low rate of abnormal fertilization
      was observed in the inseminated group of oocytes (5%) compared with 21% for the
      ICSI oocytes; this was not significantly different. Embryo development was
      assessed daily for 7 days. All normal fertilized cryopreserved oocytes in both
      groups cleaved on day 2, with a similar appearance to in-vitro fertilization and
      ICSI embryos. In the normal inseminated oocytes, there was a significant decrease
      in the number of embryos cleaving on day 3 (33%) compared with the development of
      ICSI oocytes, with a subsequent gradual reduction over days 4 and 5 (22 and 11%
      respectively) resulting in one early blastocyst on day 7 (11%). In contrast, all
      ICSI-generated embryos continued to cleave on day 3, with a gradual reduction
      over subsequent days (day 4, 86%; day 5, 57%; day 6, 43%; day 7, 29%). By day 7,
      two of the blastocysts had started to hatch, resulting in a 66% hatching rate of
      blastocysts formed from ICSI of cryopreserved oocytes. This is the first study to
      show normal development to the hatching blastocyst stage following ICSI of
      cryopreserved human oocytes.

PMID- 8567785
TI  - Intracytoplasmic sperm injection in mice: increased fertilization and development
      to term after induction of the acrosome reaction.
AB  - A technique has been developed for intracytoplasmic sperm injection (ICSI) in the
      mouse with a relatively low rate of lysis of oocytes (range 5-25% across
      experiments) and pronuclear formation in around one-third of the intact oocytes
      (range 30-38% across experiments) for untreated spermatozoa. The treatment of
      spermatozoa with calcium ionophore, to induce the acrosome reaction (increases
      acrosome-free spermatozoa from 28 to 58%) before ICSI, increased pronuclear
      formation to approximately 60% (range 59-62% across experiments) in intact
      oocytes. The pronuclear oocytes developed to blastocysts in vitro and to term
      when transferred to recipient foster mothers at rates equivalent to zygotes
      formed after insemination in vitro. There was no benefit for fertilization rates
      of activating oocytes with 8% ethanol before or after ICSI, nor was there any
      evidence of parthenogenetic activation by the sperm solution used for ICSI. This
      technique adds to other in-vitro fertilization techniques which can be used to
      explore gamete interactions and to recover breeding in infertile strains and
      reproductively unfit mice.

PMID- 8567786
TI  - Cryopreservation of human oocytes and fertilization by two techniques: in-vitro
      fertilization and intracytoplasmic sperm injection.
AB  - Human oocyte cryopreservation results in poor survival and subsequent
      fertilization rates. It has been suggested that freeze-thaw-induced changes in
      the zona pellucida may impair sperm penetration or attachment. The aim of this
      study was to compare fertilization and cleavage rates in cryopreserved oocytes
      inseminated by conventional in-vitro fertilization (IVF) or intracytoplasmic
      sperm injection (ICSI). A total of 220 oocytes, obtained from volunteers who had
      undergone ovarian stimulation, were cryopreserved using a slow freeze-rapid thaw
      protocol with 1.5 M propanediol as the cryoprotectant. Surviving oocytes (n = 74,
      34.4%) were randomly allocated for fertilization by conventional IVF (group 1) or
      ICSI (group 2) using cryopreserved spermatozoa from a single donor of proven
      fertility. Fertilization was achieved in five (13.5%) of the oocytes in group 1
      and 17 (45.9%) in group 2 (P < 0.005), with only one oocyte in group 1 exhibiting
      normal fertilization as opposed to 16 (43.2%) in group 2 (P < 0.001). Similarly,
      one oocyte fertilized by IVF cleaved, while all fertilized with ICSI cleaved (P <
      0.001). We conclude that although the survival of oocytes is poor following
      cryopreservation, fertilization and cleavage rates can be enhanced significantly
      using ICSI. These data also suggest that the method of cryopreservation used in
      this study affected the zona pellucida, such that normal sperm attachment or
      penetration was impaired.

PMID- 8567787
TI  - MUC1 in secretory phase endometrium: expression in precisely dated biopsies and
      flushings from normal and recurrent miscarriage patients.
AB  - MUC1 is a cell-surface and secretory product of endometrial epithelium.
      Immunohistochemical studies carried out using two different antibodies to the
      mucin-type tandem repeat region of MUC1 indicate a cell-surface location in
      proliferative phase glands, with intracellular deposits accumulating in the early
      secretory phase. Commencing 3-4 days after the luteinizing hormone (LH) peak and
      continuing into the late secretory phase, secretory MUC1 appears in gland lumens.
      Uterine flushings were collected as a function of time after the LH peak and were
      analysed using a two-site enzyme-linked immunosorbent assay for MUC1. Low but
      measurable concentrations were observed up to day 7, while on days 7-13 much
      higher values were obtained. In women suffering from recurrent spontaneous
      miscarriage, the concentration of MUC1 in flushings was significantly lower than
      in the controls on day LH + 10. Lower values were observed on days 7 and 13.
      Reduced epithelial secretory function and a resultant change in uterine fluid
      composition are features of endometrium from recurrent miscarriage patients.

PMID- 8567788
TI  - Reproductive outcome following hysteroscopic management of intrauterine septum
      and adhesions.
AB  - The reproductive outcome of women with repeated abortions or infertility was
      assessed following treatment by operative hysteroscopy for an intrauterine septum
      or adhesions. A prospective follow-up study (mean +/- SD, 21.1 +/- 10.3 months)
      of 47 patients with an intrauterine septum (36 suffering from infertility and 11
      from recurrent abortions) and 36 patients with intrauterine adhesions (24
      complaining of infertility and 12 of recurrent abortions) was performed. The
      pregnancy rate in infertile women following hysteroscopic resection of an
      intrauterine septum or adhesions was 53 and 48% respectively. The pregnancy
      wastage in women with recurrent abortions who underwent hysteroscopic resection
      of an intrauterine septum or adhesions decreased postoperatively from 87.5 to
      44.4% and from 86.5 to 42.8% respectively. Our results suggest that hysteroscopic
      resection of an intrauterine septum or adhesions may benefit patients suffering
      from infertility or recurrent pregnancy wastage.

PMID- 8567789
TI  - Expression of gap junction connexins in the human endometrium throughout the
      menstrual cycle.
AB  - Expression of connexins, the proteins which comprise gap junction channels, is
      regulated by ovarian hormones in the female reproductive tract of rodents. In
      order to determine if these hormones also affect connexin expression in the human
      uterus, the distribution patterns of different connexins (cx26, cx32, cx43) were
      investigated by immunohistochemistry in human endometrial tissue collected
      throughout the menstrual cycle. During the early proliferative phase of the cycle
      extremely low staining for connexin 43 was observed and connexin 26 antigens
      could not be detected. An increase in the amount of connexin 43 in stromal cells
      and of connexin 26 in glandular and luminal epithelial cells was seen from days
      11-15 of the cycle. Following ovulation, the expression of both connexins was
      suppressed and was completely abolished in the late secretory phase. Weak
      staining for connexin 32 was found mainly in the late proliferative and the early
      secretory phase and was restricted to the basal membrane region of the glandular
      cells. These results suggest that the different connexins could represent cell
      biological markers for the proliferation and differentiation of the human
      endometrium throughout the menstrual cycle.

PMID- 8567790
TI  - Peritoneal natural killer cytotoxicity and CD25+ CD3+ lymphocyte subpopulation
      are decreased in women with stage III-IV endometriosis.
AB  - We examined the lymphocytes of peripheral blood (PB) and peritoneal fluid (PF) of
      women with or without endometriosis to investigate the alteration of cytotoxic
      activity of natural killer (NK) cells and activation of T cells in the peritoneal
      cavity of women with endometriosis. A total of 16 control women and 14 patients
      with stage III-IV endometriosis were selected on the basis of laparoscopic
      examination in National Taiwan University Hospital. The lymphocyte subpopulations
      (B cell, NK cell and T cell), including T-cell activation markers (CD69, CD25,
      HLA-DR), in PB and PF were analysed by dual-colour flow cytometry. The NK
      cytotoxicity of PB and PF mononuclear cells was evaluated by 51Cr release assay.
      There was a significant decrease of NK cytotoxicity and CD25+ CD3+ lymphocyte
      subpopulation in PF of women with endometriosis compared with those without
      endometriosis. However, there was no difference in the proportion of NK cells in
      both PB and PF between women with and without endometriosis. Therefore, the
      decreased NK cytotoxicity in PF of women with endometriosis was due to the
      functional defect, but not quantitative defect, of NK cells. The concomitant
      reduction of activated T cells in women with endometriosis might suggest its
      possible role in the defect of NK cytotoxicity.

PMID- 8567791
TI  - Relationship of uterine blood flow to chorionic sac and embryo growth rates.
AB  - The embryonic period of development is characterized by marked variability in the
      rate of embryonic growth and development. Differences in uterine blood flow may
      explain this variability. We investigated the relationship between uterine artery
      blood flow volume (VOL), uterine artery pulsatility index (UA-PI), uterine artery
      resistance index (UA-RI), spiral artery pulsatility index (SA-PI), spiral artery
      resistance index (SA-RI), chorionic sac diameter (CSD), and crown-rump length
      (CRL) during 321 first trimester vaginal colour Doppler ultrasound examinations
      of 94 delivered or continuing pregnancies. After correcting for the confounding
      effect of gestational age, subject, and serum hormone levels by Analysis of
      Covariance, CRL was related to UA-PI (P = 0.025) and UA-RI (P < 0.001), but not
      to VOL, SA-PI, or SA-RI. No relationship was found between CSD and any uterine
      blood flow variables. Serum oestradiol levels were related to CSD and CRL (P <
      0.001). No relationship was found to progesterone, maternal age, parity, or
      previous abortion. We conclude that differences in uterine blood flow and serum
      oestradiol explain some of the variability in the rate of embryo growth during
      the first 12 gestational weeks.

PMID- 8567792
TI  - The measurement of CA 125 and placental protein 14 in uterine flushings in women
      with recurrent miscarriage; relation to endometrial morphology.
AB  - The concentrations of CA 125 and placental protein 14 (PP14) were measured in
      uterine flushings obtained throughout the luteal phase of the cycle from eight
      normal fertile women. The concentrations of both proteins increased in a similar
      pattern throughout the luteal phase of the cycle, with the most dramatic increase
      occurring 6 days after their luteinizing hormone surge (day LH +6). However, a
      greater variation in CA 125 concentrations was seen compared to that seen for
      PP14. The concentrations were compared to those obtained on day LH +7 of the
      cycle from a group (n = 35) of women with recurrent miscarriage. The ranges in
      concentration of PP14 and CA 125 in the flushings of fertile and recurrent
      miscarriage patients were very similar. However, a greater proportion of women
      with recurrent miscarriage (55%) had low concentrations (< 5 ng/ml) of PP14 than
      in the control group (12.5%) and the concentrations of PP14 in the uterine
      flushings were significantly less (P < 0.05) in women with recurrent miscarriage
      compared to the normal fertile group. There was no significant difference in the
      concentration of CA 125 in the uterine flushings between the two groups.
      Histological observation of the endometrial biopsy samples from recurrent
      miscarriage patients gave menstrual cycle datings that ranged from day LH +2.5 to
      LH +6.5 with retarded endometrium (< day LH +5) in 12 of 35 (34%) patients. Of
      these 12 patients, 10 (83%) had low PP14 concentrations and six (50%) had low CA
      125 concentrations in their uterine flushings. In the recurrent miscarriage
      patients with histologically normal (> or = day LH +5) endometrial development,
      10 out of 23 (43%) also had low PP14 concentrations and 8 out of 23 (35%) had low
      CA 125 in their uterine flushings. The results suggest that PP14 is better than
      CA 125 as a marker for endometrial function in this group of women. In some cases
      (52%) the low concentrations of PP14 in the uterine flushings could be explained
      by retarded endometrial development but for the others the reduction in PP14
      concentration in the uterine flushing was not associated with retardation of
      endometrial development.

PMID- 8567793
TI  - Gestational development of human placental 17 beta-hydroxysteroid oxidoreductase
      types 1 and 2.
AB  - Human placenta is a rich source of 17 beta-hydroxysteroid oxidoreductase (17-HOR)
      type 1, a cytosolic enzyme highly specific for 17 beta-oestradiol, and type 2, a
      microsomal form reactive with both oestradiol and testosterone. Although a number
      of studies have established that 17-HOR activity is present in placenta as early
      as weeks 4-5 of gestation, more specific data on the pattern of development of
      these two enzyme forms are lacking. In this study, samples of villous tissue from
      weeks 7-20 of gestation were fractionated into cytosol and microsomes and 17-HOR
      activity assayed under conditions which differentiate between the two enzyme
      types. Type 1 activity with oestradiol of cytosol and microsomal type 2 activity
      with oestradiol and testosterone increased from week 7 to week 20. Activities at
      17-20 weeks approximated those at 38-40 weeks. The high, cytosolic oestradiol/T
      activity ratio (160 +/- 20), characteristic of 17-HOR type 1, was constant
      between weeks 7 and 20, as was the low microsomal ratio (3.4 +/- 0.4)
      characteristic of the type 2 activity. There was a relationship between cytosolic
      type 1 activity and microsomal type 2 activity between weeks 7 and 20 (r = 0.59,
      P = 0.0055). These results indicate both activities increase coincident with the
      luteal-placental shift and that their temporal patterns of development are
      related between weeks 7 and 20 of gestation.

PMID- 8567794
TI  - Placebo-controlled trial of treatment of unexplained secondary recurrent
      spontaneous abortions and recurrent late spontaneous abortions with i.v.
      immunoglobulin.
AB  - The aim of this trial was to investigate whether infusions of i.v.
      immunoglobulins (Ig) to women with secondary recurrent spontaneous abortions and
      recurrent second trimester spontaneous abortions can increase the rate of
      successful pregnancy. In a prospective, double-blind, placebo-controlled trial,
      infusions of i.v. Ig (Nordimmun) or placebo were given during pregnancy to 34
      women with a history of either unexplained recurrent spontaneous abortion
      subsequent to a birth or including at least one second trimester miscarriage. The
      success rate was 52.9% in the i.v. Ig group compared with 29.4% in the placebo
      group (not significantly different, therapeutic gain 23.5%, 95% confidence
      interval -8.6 to 55.7%). No changes in autoantibody concentrations or major
      lymphocyte subsets were induced by i.v. Ig treatment. In conclusion, an expected
      55% therapeutic gain of i.v. Ig in recurrent spontaneous abortion could not be
      confirmed using the treatment regimen tested. However, to determine whether the
      trend of therapeutic gain of i.v. Ig in these women may be statistically
      significant, a larger trial is in progress.

PMID- 8567795
TI  - Fetal loss in the first trimester after demonstration of cardiac activity:
      relation of cytogenetic and ultrasound findings.
AB  - A retrospective comparison of cytogenetic and ultrasound findings in first
      trimester spontaneous fetal loss after demonstration of cardiac activity was
      made. The crown-rump length (CRL) was measured twice for each fetus resulting in
      spontaneous abortion: (i) CRL was measured in the viable state while
      demonstrating cardiac activity, and the growth deviation was expressed as the
      measured/expected CRL ratio (M/E CRL ratio); (ii) in the same fetus, CRL was
      measured after confirmation of fetal death, and designated as the post-mortem
      CRL. The chorionic tissues of these abortuses were karyotyped. The CRL of fetuses
      which resulted in normal deliveries were also measured as controls. As a result,
      16 of 24 abortuses displayed an abnormal chromosomal analysis (67%). The mean M/E
      CRL ratio of still-viable fetuses was smaller than that of control fetuses (0.74
      +/- 0.20 versus 0.98 +/- 0.13 respectively, P < 0.01). The differences in ratio
      between karyotypically normal and abnormal abortuses were not statistically
      significant. The post-mortem CRL of dead fetuses was > 20 mm in four of five
      monosomy X, two of three 21-trisomy, one of three triploidy and none of eight
      embryos with normal karyotype and five other trisomies. In conclusion, our study
      demonstrated that the M/E CRL ratio could be used as a predictor of spontaneous
      abortions, although it does not discriminate abnormal karyotypes from normal
      ones. The embryos with a post-mortem CRL more than 20 mm have a higher likelihood
      of suffering monosomy X or 21-trisomy. The ultrasonographic findings might offer
      a cytogenetic clue as to a possible cause to the developmental arrest.

PMID- 8567796
TI  - Relationships between the uterine environment and maternal plasma concentrations
      of insulin-like growth factor binding protein-1 and placental protein 14 in early
      pregnancy.
AB  - Blood was obtained from 218 women between 6 and 13 weeks of gestation.
      Measurements of serum insulin-like growth factor binding protein-1 (IGFBP-1) and
      placental protein 14 (PP14) concentrations were compared with maternal weight and
      height, maternal smoking habit, indices of maternal haematological status and two
      placental hormones [human chorionic gonadotrophin (HCG) and human placental
      lactogen (HPL)]. IGFBP-1 concentration was negatively correlated with maternal
      weight (P < 0.001) and body mass index (P < 0.001); PP14 concentration was not
      correlated with these measurements. PP14 concentration was negatively correlated
      with maternal haemoglobin concentration (P = 0.010), mean corpuscular volume (P =
      0.003) and serum ferritin concentration (P = 0.016). The concentrations of PP14
      were significantly less among smokers (P < 0.001); IGFBP-1 concentrations were
      uninfluenced by smoking. IGFBP-1 concentration was positively correlated with
      maternal serum HCG (P = 0.003) and maternal serum HPL (P = 0.002). PP14
      concentration was positively correlated with maternal serum HCG (P < 0.0001) but
      not with HPL. These findings demonstrate that the maternal environment has an
      early influence on both endometrial and placental function.

PMID- 8567797
TI  - Weight loss results in significant improvement in pregnancy and ovulation rates
      in anovulatory obese women.
AB  - Obesity can affect ovulation and the chances of pregnancy. In this prospective
      study, a weight loss programme was assessed to determine whether it could help
      infertile overweight anovulatory women to establish ovulation and assist in
      achieving pregnancy, ideally without further medical intervention. The subjects
      acted as their own historical controls. They underwent a weekly programme of
      behavioural change in relation to exercise and diet over 6 months; those who did
      not complete the 6 months were treated as the comparison group. Women in the
      study group lost an average of 6.3 kg, with 12 of the 13 subjects resuming
      ovulation and 11 becoming pregnant, five of these spontaneously. Fitness, diet
      and psychometric measurements all improved. Fasting insulin and testosterone
      concentrations dropped significantly, while sex hormone binding globulin
      concentrations rose. None of these changes occurred in the comparison group.
      Thus, weight loss with a resultant improvement in ovulation, pregnancy outcome,
      self-esteem and endocrine parameters is the first therapeutic option for women
      who are infertile and overweight.

PMID- 8567798
TI  - Obstetric outcome of 424 pregnancies after intracytoplasmic sperm injection.
AB  - An evaluation of the outcome of pregnancies resulting from intracytoplasmic sperm
      injection for severe male factor infertility was conducted by analysing the data
      obtained from the patients and/or their obstetrician/gynaecologist on
      standardized questionnaires. The data from 424 pregnancies between April 1991 and
      September 1994 were analysed. Early pregnancy loss before 16 weeks occurred in 99
      cases (23.3%), including 48 clinical abortions (11.3%), 47 subclinical
      pregnancies (11.1%) and four ectopic pregnancies (0.9%). Vanishing twins and
      triplets, which could be regarded as early embryonic wastage, were found in 36
      cases (8.5%). One pregnancy was interrupted at week 15 of gestation because of
      anhydramnios, and four pregnancies (0.9%) ended in spontaneous late abortions
      before 26 weeks. A total of 320 pregnancies (75.5%) resulted in the birth of at
      least one child; 222 of these (69.3%) were singletons, 93 were twins (29.1%) and
      five were triplets (1.6%). The problems of prematurity and low birthweight were
      especially related to the multiplicity of pregnancies. Furthermore, from among
      the total of 423 babies born, we have observed three cases of stillbirth and five
      cases of neonatal mortality. The perinatal mortality rate was therefore 18.9 per
      1000 births. The results of this study show that the obstetric outcome of these
      pregnancies was similar to that obtained after conventional in-vitro
      fertilization and other assisted reproduction techniques.

PMID- 8567799
TI  - Identification of hormonal parameters for successful systemic single-dose
      methotrexate therapy in ectopic pregnancy.
AB  - Single-dose methotrexate is an alternative to surgery in treating ectopic
      pregnancy. Because success rates vary, we sought to identify factors which
      predict treatment outcome. A total of 44 women with ectopic gestation were
      treated. The non-laparoscopic diagnosis of ectopic pregnancy was made following
      history, physical examination, ultrasound, endometrial biopsy and the measurement
      of serial beta-human chorionic gonadotrophin (HCG) and progesterone
      concentrations. Methotrexate (50 mg/m2 i.m.) was administered, with a second dose
      given 1 week later in patients with plateauing or rising beta-HCG concentrations.
      Of 44 patients, 23 (52.3%) were successfully treated with one dose. An additional
      10 women (22.7%) were also successfully managed but required a second dose,
      giving an overall success rate of 75.0%. In all, 11 women (25.0%) required
      surgery, four of whom experienced tubal rupture. Receiver operator curves were
      constructed to optimally select pretreatment beta-HCG and progesterone cut-off
      concentrations for successful treatment. Using beta-HCG < 1500 IU/l or
      progesterone < 7.0 ng/ml (22.3 nmol/l) as a cut-off concentration produced a
      diagnostic test with a sensitivity of 87.5%, a specificity of 90.0%, a positive
      predictive value of 96.6% and a negative predictive value of 69.2%. Conversely,
      this model predicts that patients with serum beta-HCG concentrations > or = 1500
      IU/l and progesterone concentrations > or = 7.0 ng/ml are at far greater risk of
      failing single-dose methotrexate therapy.

PMID- 8567800
TI  - Pre-eclampsia-like conditions produced by nitric oxide inhibition: effects of L
      arginine, D-arginine and steroid hormones.
AB  - The aim of this study was to establish that inhibiting nitric oxide (NO)
      production with NG-nitro-L-arginine methyl ester (L-NAME) results in high blood
      pressure conditions in chronically treated pregnant rats. To validate the model,
      the effects of L-arginine (the substrate for NO) and D-arginine (the stereoisomer
      of L-arginine which is not a substrate for NO synthesis) were studied on blood
      pressure and fetal weights. The effects of a progesterone agonist, promegestone
      (R5020) and 17 beta-oestradiol were also explored. The NO synthase inhibitor L
      NAME was chronically infused s.c. into pregnant rats from day 17 of gestation,
      either alone or with the simultaneous infusion of L-arginine and injections of
      sex steroid hormones (promegestone and oestradiol), compounds that may act in the
      pathogenic pathways of pre-eclampsia. Systolic blood pressure was measured daily.
      Weight and mortality of pups were recorded immediately after delivery. Blood
      pressure was elevated significantly in rats treated with L-NAME for only 1 day
      following infusion; there was a consistent decline during the next 3 days of
      pregnancy followed by a dramatic and significant rise just prior to delivery and
      post-partum. Fetal weights were reduced significantly in the L-NAME-treated rats.
      Co-treatment of L-NAME-infused rats with L-arginine reversed both the increase in
      blood pressure and the decrease in fetal weights observed with L-NAME alone.
      R5020, but not oestradiol, also reduced blood pressure and increased fetal
      weights in the L-NAME-treated animals. NO appears to play essential roles in the
      regulation of blood pressure during pregnancy, as well as in fetal perfusion and
      fetal weights at delivery. This study also indicates that progesterone, and not
      oestrogen, may regulate the vascular adaptations during normal pregnancy. L
      Arginine and progesterone agonists like promegestone may have beneficial effects
      on the high blood pressure levels and reduced fetal weights associated with pre
      eclampsia.

PMID- 8567801
TI  - Lesbian mothers who conceived after donor insemination: a follow-up study.
AB  - This study investigated the development of family relationships in lesbian
      families who conceived after donor insemination (DI). The main characteristics of
      this unknown family structure were analysed. An anonymous donor was used to
      conceive, the family unit consisted of two mothers and a father was non-existent,
      and both women had a homosexual orientation. A total of 50 lesbian couples who
      conceived after DI with children aged between 1 and 2 years participated in this
      study, using a standardized interview created for this study. After the birth of
      their child, 56% of the lesbian mothers (n = 100) would have wanted the identity
      of the donor to be registered, while 10% would have done so at the time of the
      insemination. Opinions differed in 12 of the 50 couples: the biological mother
      was in favour of identity registration while the social mother was not. Both
      women considered themselves a parent of the child with equally shared
      responsibilities. Mothers were open about the special features of their family
      structure with children and within their immediate social network. Only 30%
      disclosed their lesbian identity in a broader social environment. The features of
      these newly created families may influence the psychological development of the
      children and therefore make long-term follow-up studies indispensable.

PMID- 8567802
TI  - Should donors have the right to decide who receives their gametes?
AB  - A continuing feature of gamete donation is the scarcity of available donors. A
      strategy to improve the meagre supply of gametes would be to adjust the donation
      procedure to the wishes and desires of the donors. However, giving donors the
      right to direct their gametes to certain groups of recipients goes against the
      general rule that donors relinquish all rights and duties. Moreover, allocation
      by the donor might very well run counter to the rules of distributional justice.
      On the other hand, the allocation right can be supported by the principle of
      autonomy and by the donor's interest in and contribution to the process. The
      position is taken that the donors should have the right to direct their gametes
      to categories accepted as relevant by the moral and religious communities in
      their society. They should not be given the right to add their own categories to
      the exclusion list. If donors are not allowed to allocate their gift, they should
      at least be informed as to which categories of recipient are treated by the
      hospital to enable them to decide whether they want to donate gametes.

PMID- 8567803
TI  - Follow-up study of anonymous ovum donors.
AB  - A follow-up study was conducted to determine the emotional and medical responses
      of anonymous ovum donors to participation in an ovum donation procedure.
      Medically, donors reported significant discomfort, particularly relating to
      bloating, immediately prior to retrieval and for a brief period following
      retrieval. However, donors indicated that these effects no longer persisted at
      the time of follow-up. They also mentioned how unusual and initially anxiety
      arousing it was to be in charge of their own injections. Few donors reported
      serious adverse emotional responses; many reported positive emotional responses
      to participation. Donors felt proud of their contribution, talked about their
      participation with friends and relatives, would be willing to participate again
      and would recommend ovum donation to other women. However, since the sample
      included only 43% of the 74 women who donated, caution is necessary in
      generalizing from the results of our study.

PMID- 8567804
TI  - Multiple births in couples with infertility problems.

PMID- 8567805
TI  - Multiple births in couples with infertility problems.

PMID- 8567806
TI  - Multiple births in couples with infertility problems.

PMID- 8567807
TI  - Intravenous albumin and the prevention of severe ovarian hyperstimulation
      syndrome.

PMID- 8567808
TI  - A survey of semen donation: phase II the view of the donors.

PMID- 8567809
TI  - Changes in the sialylglycoconjugate distribution on the human sperm surface
      during in-vitro capacitation: partial purification of a 20 kDa sialylglycoprotein
      of capacitated spermatozoa.
AB  - Changes in the distribution of sialylglycoconjugates on the surface of
      uncapacitated and in-vitro capacitated human spermatozoa were studied by means of
      two sialic acid specific lectins (Maackia amurensis agglutinin and Sambucus nigra
      agglutinin). On the uncapacitated sperm surface, sialylglycoconjugates were found
      to be localized from the post-acrosomal region of the sperm head to the tail
      middle piece, whereas after in-vitro capacitation these molecules were only found
      in a small area of the post-acrosomal region. The surface of capacitated human
      spermatozoa was also investigated by specifically radiolabelling its terminal
      sialic acid residues. A 20 kDa glycoprotein, which was partially purified by
      anion-exchange chromatography, was the main component of the sialylglycoconjugate
      pattern after in-vitro capacitation.

PMID- 8567810
TI  - Human endometrial proteins with cyclic changes in the expression during the
      normal menstrual cycle: characterization by protein sequence analysis.
AB  - Endometrial proteins showing cyclic expression during the normal menstrual cycle
      were localized on two-dimensional (2-D) electrophoresis gels separating proteins
      with isoelectric points (pl) ranging from 3.5 to 7 and relative molecular weights
      ranging from 10 to 300 kDa. Menstrual cycle-related proteins were excised from
      several 2-D gels, concentrated by one-dimensional (1-D) sodium dodecyl sulphate
      (SDS)-polyacrylamide gel electrophoresis, and cleaved in situ by trypsin. The
      tryptic fragments were extracted and separated by reverse phase high performance
      liquid chromatography (RP-HPLC). Finally, the partial amino-terminal amino acid
      sequence of selected tryptic fragments were determined for each protein. We aimed
      at characterizing the 21 menstrual cycle-related proteins that were visible on
      silver-stained 2-D electrophoresis gels. Of the proteins being maximally
      synthesized in the proliferative phase endometrium, we identified proteins
      associated mainly with the cytoskeleton: vimentins, keratin, tropomyosin and
      tubulin, but also proteins such as proliferating cell nuclear antigen and beta
      galactoside binding lectin. The partial amino acid sequences for another two
      proteins did not match any protein sequence in the Protein Identification
      Resource (PIR) and Swissprot databases. In the group of proteins having maximal
      synthesis in the secretory phase endometrium, we identified creatine kinase chain
      B and an isocitrate dehydrogenase-homologous protein, both of which are involved
      in energy metabolism. However, we also identified the annexin IV precursor, the
      14-3-3 protein homologue also called stratifin or the epithelial cell marker
      protein 1 and the 21K tumour protein. Finally, four of the proteins were present
      in too low amounts to allow characterization. Interestingly, most of the
      identified proteins have not previously been described as having a menstrual
      cycle-related synthesis in the human endometrium. It may be considered that the
      concentration of some of the cycle-related proteins may be used in clinical
      situations to reflect specific endometrial phases.

PMID- 8567811
TI  - Effects of epidermal growth factor, transforming growth factor alpha and
      androstenedione on follicular growth and aromatization in culture.
AB  - The effects of epidermal growth factor (EGF), transforming growth factor alpha
      (TGF alpha) and androstenedione on follicular growth and oestradiol production
      were studied in cultured mouse preantral follicles. Cultured follicles in the
      control group showed growth and steroidogenic capacities up to the antral
      follicle stage at day 4 of culture. However, many of these follicles failed to
      resume their growth during the culture. Increasing concentrations of EGF and TGF
      alpha decreased the number of follicles reaching the large antral stage at day 4
      of culture. All treatments with EGF, TGF alpha and androstenedione caused
      significant inhibitions in both follicular growth and oestradiol production,
      regardless of the dose used (1-20 ng/ml). Moreover, no synergistic effect between
      androstenedione and either of the two growth factors was observed. These results
      suggest that EGF, TGF alpha and/or androstenedione may play important roles in
      the modulation of gonadotrophin-controlled ovarian function. The effects observed
      in this study suggest that the aberration in the regulation of these growth
      factors may result in the creation and maintenance of certain ovarian disorders,
      such as the polycystic ovarian disease.

PMID- 8567812
TI  - Stimulation of prostaglandin (PG) F2 alpha and PGE2 release by tumour necrosis
      factor-alpha and interleukin-1 alpha in cultured human luteal phase endometrial
      cells.
AB  - Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) are
      important mediators of cell signalling in the uterus. Prostaglandins (PG) have
      been implicated in the increase of endometrial vascular permeability which occurs
      during the implantation process. This study evaluates the effect of these two
      pleiotropic cytokines on PGF2 alpha and PGE2 release from human luteal phase
      endometrial glandular epithelial cells (GEC) and stromal cells (STC) in culture.
      Basal PGF and PGE release did not differ significantly from each other or among
      cell types, and declined significantly with increasing number of days in culture.
      On day 3, basal PG release had decreased to half of that on day 1 of culture.
      However, both cell types were still able to respond to the addition of exogenous
      arachidonic acid (5 microM) on day 3 of culture, with PG release by GEC being
      elevated 7- to 10-fold and by STC moderately, but still significantly, on day 4.
      The permissive effect of arachidonic acid on the stimulation of PG release may
      indicate the down-regulation of phospholipase A2 with continued time in culture.
      However, the addition of arachidonic acid (5 microM) on day 0 of culture, while
      able to cause significantly increased PG release from GEC, had no effect on STC.
      In contrast, the addition of a combination of arachidonic acid (5 microM), and
      either recombinant human TNF-alpha (10 micrograms rhTNF-alpha/l) or 10 micrograms
      rhIL-1 alpha/l, had a synergistic action and caused the significantly increased
      release of PGF and PGE from both cell types, compared with that achieved with
      either arachidonic acid or the cytokine alone (although GEC responded more than
      STC). During the first 24 h after the addition of rhTNF-alpha or rhIL-1 alpha,
      both cytokines stimulated PG release from both cell types in a dose- and time
      dependent fashion. Neither cycloheximide (10 microM) nor actinomycin D (10
      microM) affected basal PG release, but both blocked cytokine-induced PG release
      from both cell types. These results suggest that there is a differential control
      of human endometrial cell PG biosynthesis, and that PG release may be regulated
      through gene activation.

PMID- 8567813
TI  - Human oviductal cells produce high molecular weight factor(s) that improves the
      development of mouse embryo.
AB  - The coculture effects of human oviductal cells on mouse embryo development in
      vitro were studied. Pronuclear stage mouse zygotes were cocultured with different
      cell types, or then cultured either in medium alone (control), spent medium from
      oviductal cell culture (conditioned medium) or high molecular weight fractions (>
      10 and > 100 kDa) of the conditioned medium (reconstituted medium). Embryotrophic
      activities were compared between these groups in terms of percentage of morula
      and blastocyst formation, and cell count at the blastocyst stage. The mouse
      embryos developed better in oviductal cell coculture than in fibroblast coculture
      and medium alone culture. Conditioned medium and its reconstituted medium also
      provided a significant enhancement of embryo development in vitro when compared
      with the control medium culture, suggesting the production of high molecular
      weight embryotrophic factor(s) by the oviductal cells. The high molecular weight
      embryotrophic activity accumulated with the duration of conditioning could be
      serially diluted, and was abolished by heat or trypsin treatment. Replacing
      bovine serum albumin with polyvinyl alcohol in the culture medium did not affect
      the production of this high molecular weight embryotrophic activity by oviductal
      cells.

PMID- 8567814
TI  - Expression of transcription regulating genes in human preimplantation embryos.
AB  - Utilizing a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR)
      assay system, the time course of mRNA expression of two transcription regulators,
      OCT4 and OCT6, was assessed in individual preimplantation human embryos.
      Examination of ova with three pronuclei and 1-cell through blastocyst stage
      embryos revealed that OCT4 mRNA was continuously expressed between the time of
      fertilization and 10+ cell stages, whereas OCT6 mRNA expression was not observed
      until the 10+ cell stage. The difference in the time of expression of OCT4 mRNA
      and OCT6 mRNA indicates that the two genes play differential roles in human
      embryogenesis. Nucleotide sequence homology for OCT4 and OCT6 among mammalian
      organisms supports the concept that genetic elements determining developmental
      events during embryogenesis are conserved in evolution.

PMID- 8567815
TI  - Progressive rise in the expression of interleukin-6 in human endometrium during
      menstrual cycle is initiated during the implantation window.
AB  - In order to be prepared for implantation, human endometrium undergoes a
      predictable series of proliferative and secretory changes. Cytokines play an
      important role in regulation of these changes. Therefore, in this study, we
      immunolocalized the cytokine, interleukin-6 (IL-6), its receptor and the signal
      transducer gp130 in human endometrium throughout the menstrual cycle. During the
      entire menstrual cycle, the IL-6 receptor and gp130 were found primarily in the
      endometrial glands and to a lesser extent in the stroma. The immunoreactivity of
      these proteins did not change in endometrial cells during the entire menstrual
      cycle with an exception of reduced immunoreactivity of gp130 in endometrial
      glands during menstrual phase. Immunostaining showed that immunoreactive IL-6 was
      weakly expressed in human endometrium during the proliferative phase. Strong
      immunoreactivity for IL-6 appeared in endometrium during the putative
      'implantation window'. Expression was by far most pronounced both in the
      glandular and surface epithelial cells. The amount of immunoreactive IL-6 in the
      epithelium progressively increased during the secretory/menstrual phases. During
      the late secretory phase, only stromal cells in the upper functionalis exhibited
      immunoreactivity for IL-6. Western blot analysis corroborated the
      immunohistochemical data. Human endometrial IL-6 consisted of a protein with an
      apparent mobility of 26 kDa. The immunoreactive band of IL-6 was weak in the
      proliferative phase. The expression of this protein increased progressively
      during the secretory/menstrual phases. The findings show a cell-specific pattern
      of distribution for immunoreactive IL-6 in human endometrium. The menstrual cycle
      dependent expression of IL-6 suggests that this cytokine may play a role in
      changes in endometrium that prepare this tissue for implantation and menstrual
      shedding.

PMID- 8567817
TI  - Increased follicle stimulating hormone in infertile men. Is increased plasma FSH
      always due to damaged germinal epithelium?

PMID- 8567816
TI  - Secretion of colony stimulating factor-1 by human first trimester placental and
      decidual cell populations and the effect of this cytokine on trophoblast
      thymidine uptake in vitro.
AB  - The present in-vitro study using an enzyme-linked immunosorbent assay has
      identified the cell types responsible for colony stimulating factor-1 (CSF-1)
      production at the first trimester human placental uterine interface. The major
      sources were observed to be decidual stromal cells and decidual CD56+ natural
      killer (NK) cells, but decidual CD3+ T cells did not produce CSF-1, reflecting
      functional differences between these two decidual lymphoid populations. Of a
      variety of cytokines tested, only interleukin-2 (IL-2) was found to augment CSF-1
      secretion by decidual NK cells. Trophoblast cells also secreted CSF-1, but the
      amounts were small relative to decidual stromal cells and NK cells. Therefore,
      most of the CSF-1 present at the implantation site appears to be maternally
      derived. Co-culture of decidual NK cells on a monolayer of irradiated trophoblast
      did not augment CSF-1 secretion by decidual NK cells, indicating that the
      production of this cytokine is not stimulated by contact with fetal trophoblast.
      CSF-1 was found to increase [3H]thymidine uptake by trophoblast cultured on
      laminin for 72 h, but no such response was seen in trophoblast cultured on
      fibronectin, indicating that these extracellular matrix proteins have
      differential effects on the response of trophoblast to this cytokine.

PMID- 8567818
TI  - Whither the investigation of male infertility? Is FSH measurement redundant and
      should all azoospermic patients have testicular biopsy?

PMID- 8567819
TI  - Human Sertoli cells produce inhibin in vitro: an additional marker to assess the
      seminiferous epithelium development.

PMID- 8567820
TI  - Increased follicle stimulating hormone in infertile men. Guidelines for diagnosis
      and therapy.

PMID- 8567821
TI  - Insulin resistant and non-resistant polycystic ovary syndrome represent two
      clinical and endocrinological subgroups.
AB  - We studied the clinical and endocrine features of 35 patients with polycystic
      ovary syndrome (PCOS) who are either insulin resistant or non-insulin resistant.
      The occurrence of insulin resistance was determined by measuring insulin and
      glucose concentrations following a standard 75 g oral glucose load. All patients
      were evaluated by anthropometric measurements: body mass index (BMI), percentage
      of body fat (BCF) and waist-to-hip ratio (W/H), degree of hirsutism (Ferriman
      Gallwey method) and endocrine profile. Fourteen patients had insulin resistance
      of unknown origin whereas four were due to a type A insulin receptor mutation,
      and 17 were non-insulin resistant. The insulin resistant patients were
      significantly more obese (higher BMI P < 0.0001, BCF P < 0.002 and W/H ratio P <
      0.005) and were more hirsute (P < 0.002) than the non-insulin resistant patients.
      Testosterone concentrations were significantly higher in the insulin resistant
      group than in the non-insulin resistant group (2.65 versus 1.37 nmol/l; P <
      0.027), whereas sex hormone-binding globulin was lower in insulin resistant
      patients (30.61 versus 19.48 nmol/l; P < 0.02). Non-insulin resistant patients
      showed a high luteinizing hormone to follicle stimulating hormone ratio, while a
      normal ratio was found in the insulin resistant subpopulation (2.94 versus 1.34;
      P < 0.0001). We concluded that PCOS comprises two subpopulations, one with
      insulin resistance of different aetiologies and the other which has no insulin
      resistance. These two groups differ in their anthropometric and endocrine
      features. The diagnosis of insulin resistance in PCOS can be easily determined by
      the insulin response to an oral glucose tolerance test.

PMID- 8567822
TI  - Luteinizing hormone pulsatile release and the length of lactational amenorrhoea.
AB  - The pattern of luteinizing hormone (LH) pulsatile release and the mean
      concentrations of follicle-stimulating hormone, oestradiol and progesterone were
      studied in nursing and non-nursing women. Blood samples were drawn at 5 min
      intervals between 10:00 and 14:00 h and between 22:00 and 02:00 h at months 3-4,
      5-6, 7-8 and 9-10 postpartum in nursing women and in the follicular phase in non
      nursing women. In nursing women, mean LH concentrations at months 3-4 were
      significantly lower than in non-nursing cycling women only in the subgroup which
      subsequently experienced > 6 months of lactational amenorrhoea, although all were
      fully nursing with a similar suckling frequency. LH pulses in plasma were found
      at all times in nursing women. There were no significant differences in the
      frequency (about four pulses every 4 h), amplitude or duration of LH pulses
      related to the duration of amenorrhoea, nor did these parameters vary
      significantly between amenorrhoeic or cycling nursing women and non-nursing
      women. Nursing amenorrhoeic women exhibited a normal frequency of LH pulse well
      in advance of the resumption of the first post-partum menses, suggesting that
      mechanisms other than the suppression of the gonadotrophin-releasing hormone
      pulse generator intervened in the inhibition of ovarian function during
      lactation.

PMID- 8567823
TI  - High incidence of embryo transfer cancellations in patients with polycystic
      ovarian syndrome.
AB  - This study was aimed at assessing the outcome of in-vitro fertilization (IVF) and
      embryo transfer in patients with polycystic ovarian syndrome (PCOS). The results
      of IVF and embryo transfer in PCOS patients (PCOS group, 78 cycles of 26
      patients) were compared with those of a control group (423 cycles in 202 patients
      without male factor; age and ovarian stimulation protocol were matched). Although
      the pregnancy rate per transfer was not different in the two groups of patients
      (25 versus 34%, PCOS versus control group), the PCOS group had a significantly
      lower pregnancy rate per follicle aspiration (19 versus 31%, P < 0.05). A notable
      result was a significantly higher incidence of embryo transfer cancellations in
      the PCOS group (22 versus 8%, P < 0.01), which resulted from unpredictable
      failure of either oocyte recovery or fertilization. The incidence of unexplained
      complete failure of fertilization was significantly higher in the PCOS group (18
      versus 5%, P < 0.01). These results may reflect a reduced quality of the oocytes
      in the PCOS group, and there was a subgroup of PCOS patients who repeatedly
      produced poor results of treatment. Although the ovarian stimulation regimen best
      suited to PCOS patients remains to be determined, special care should be taken
      during ovarian stimulation, especially when the PCOS patients had experienced
      unexplained failure of oocyte recovery or fertilization in the previous treatment
      cycle(s).

PMID- 8567824
TI  - Somatostatin action on rat ovarian steroidogenesis.
AB  - To date, very few studies on the effect of somatostatin on female reproductive
      function have been reported. In our study, we examined the effects of
      somatostatin on (i) androgen biosynthesis using whole ovarian dispersates, and
      (ii) aromatase activity and progesterone production using granulosa cells. Whole
      ovarian dispersates obtained from immature rats were cultured for 96 h in serum
      free medium with human chorionic gonadotrophin (HCG; 25 ng/ml) and insulin (10
      micrograms/ml) in the presence or absence of an increasing concentration of
      somatostatin (0.03-3.00 ng/ml). HCG- and insulin-stimulated accumulation of
      androsterone by these cells was inhibited significantly by somatostatin.
      Granulosa cells from diethylstilbestrol-treated rats were cultured for 48 h in
      serum-free medium with follicle-stimulating hormone (FSH; 20 ng/ml) and FSH plus
      insulin (1 microgram/ml) with or without somatostatin (0.03-3.00 ng/ml). Both
      aromatase activity and progesterone production stimulated by FSH and FSH plus
      insulin were significantly inhibited by somatostatin. Somatostatin by itself (1
      ng/ml) did not have an effect on any of the evaluated parameters. The action of
      somatostatin could be immunoneutralized and did not influence the plated viable
      cell mass. These findings indicate that somatostatin can regulate ovarian
      steroidogenesis by mediating gonadotrophin and growth factor action on different
      ovarian cell types.

PMID- 8567825
TI  - Development and applications of luteinizing hormone-releasing hormone antagonists
      in the treatment of infertility: an overview.
AB  - Luteinizing hormone-releasing hormone (LHRH) plays a crucial role in controlling
      the ovarian cycle in women. By modification of the molecular structure of this
      decapeptide, analogues were synthesized with agonistic or antagonistic effects on
      the gonadotrophic cells of the anterior pituitary gland. The agonists, after an
      initial stimulatory effect ('flare up'), lead to desensitization of the
      gonadotrophic cells and a reduction in the number of LHRH receptors on the cell
      membrane ('down-regulation'), while the antagonists produce an immediate effect
      by competitive blockade of the LHRH receptors. After administration of LHRH
      antagonists, the serum levels of FSH and LH decrease within hours. Nevertheless,
      the adenohypophysis maintains its responsiveness to an LHRH stimulus ('pituitary
      response') after pretreatment with an antagonist. This different pharmacological
      mechanism of LHRH antagonists makes possible new approaches to ovarian
      stimulation and to the therapy of sex steroid dependent diseases. The premature
      LH surge, the main cause of cancellation during induction of superovulation in
      assisted reproduction technology (ART) programmes, can be abolished by short term
      application of an LHRH antagonist associated with a reduced human menopausal
      gonadotrophin (HMG) requirement for ovarian stimulation. A future approach to ART
      might be based on the combination of pretreatment with an LHRH antagonist and
      ovulation induction by native LHRH or an agonist. The severe side effects
      encountered with early LHRH antagonists, such as anaphylactoid reactions due to
      histamine release, are almost completely eliminated in modern antagonists,
      especially Cetrorelix which is presently used clinically in controlled phase II
      clinical studies.

PMID- 8567826
TI  - Variability in the immunoreactive and bioactive follicle stimulating hormone
      content of human urinary menopausal gonadotrophin preparations.
AB  - The within- and between-batch variation in the immunoreactive and in-vitro
      bioactive FSH content of Pergonal, Metrodin and Metrodin-HP was investigated.
      Three batches of Pergonal and Metrodin, consisting of three ampoules in each
      batch, and three batches of Metrodin-HP, consisting of between one and three
      ampoules per batch, were selected at random. The follicle stimulating hormone
      (FSH) content of Pergonal, Metrodin and Metrodin-HP was determined by
      radioimmunoassay (R-FSH) and the in-vitro rat Sertoli cell bioassay (B-FSH) using
      the international urinary standard 70/45. The variability in the FSH content of
      the preparations was evaluated within and between batches by analysis of
      variance. Within-batch variability of B-FSH was not observed in Pergonal or
      Metrodin-HP but was seen in two batches of Metrodin in which the potency varied
      by up to 2.4 fold (P = 0.03). The between-batch R-FSH potencies of Pergonal (P1
      P3) varied, with P2 (59.8 +/- 0.6) and P3 (61.7 +/- 0.9) being higher than P1
      (47.1 +/- 1.5 mean +/- SEM IU/ampoule, P < 0.01). A similar pattern of
      variability was observed for B-FSH. For Metrodin, each of the batch R-FSH
      potencies was dissimilar (P < 0.02), with estimates ranging from 34.9 +/- 1.2 to
      64.3 +/- 1.8 IU/ampoule. Furthermore, the extensive within-batch B-FSH variation
      from two batches confounded any meaningful comparison of between-batch
      variability. For Metrodin-HP, there was no between-batch B-FSH variation (29.0 +/
      6.1 to 33.0 +/- 0.3 IU/ampoule) and the R-FSH content was also well controlled
      (41.2 +/- 0.5 to 46.9 +/- 1.1 IU/ampoule).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567827
TI  - Follicle stimulating hormone-granulosa cell axis involvement in the
      antifolliculotrophic effect of low dose mifepristone (RU486).
AB  - This study was designed to assess the involvement of follicle stimulating hormone
      (FSH)-granulosa and luteinizing hormone (LH)-theca axes in the
      antifolliculotrophic effect of mifepristone. Plasma gonadotrophins, including
      plasma LH bioactivity and pulsatility, oestradiol, testosterone and inhibin
      concentrations, and follicular growth were monitored in volunteer women treated
      with placebo or mifepristone in two consecutive cycles. Mifepristone was given
      either as a single dose of 5 mg (n = 7) when the leading follicle had reached a
      diameter between 12 and 14 mm, or as a multiple dose of 5 mg/day for 3 days,
      beginning when the leading follicle had reached a diameter between 14 and 16 mm
      (n = 5) or between 6 and 11 mm (n = 5). Following the single dose of
      mifepristone, follicular growth and the accompanying increase in plasma
      oestradiol were arrested at 12 and 36 h respectively without changes in
      gonadotrophin or testosterone serum concentrations. The 3 day regimen arrested
      follicular growth and oestradiol rise and decreased plasma inhibin concentrations
      when follicles were larger than 12 mm at the onset of treatment. These results
      indicate that the antifolliculotrophic action of mifepristone is associated with
      a selective compromise of the FSH-granulosa axis of dominant follicles that have
      passed a critical stage of growth.

PMID- 8567828
TI  - Ovarian stromal blood flow in women with polycystic ovaries--a possible new
      marker for diagnosis?
AB  - Blood flow changes in the ovarian stroma of women embarking on in-vitro
      fertilization treatment were assessed on day 2 or 3 of the menstrual cycle using
      colour and pulsed Doppler ultrasound. Women were divided into three groups: group
      1, 63 women with regular, ovulatory menstrual cycles and normal ovaries on
      ultrasound scan; group 2, 13 women similar to group 1 but with polycystic ovaries
      (PCO) on ultrasound scan; and group 3, 12 women with biochemical evidence of
      previous anovulatory cycles and/or oligomenorrhoea and/or elevated serum
      luteinizing hormone concentrations (> 10 IU/l) in the early follicular phase
      together with PCO on ultrasound scan. A subjective assessment of the intensity
      and quantity of coloured areas in the ovarian stroma appeared to be greater in
      both groups 2 and 3 compared with group 1. Mean (SEM) ovarian stromal peak
      systolic blood flow velocity (Vmax) was 16.88 (1.79) and 16.89 (2.36) cm/s in
      groups 2 and 3 respectively. These velocities were significantly greater than the
      mean (SEM) ovarian stromal Vmax of group 1; 8.74 (0.68) cm/s (P < 0.001). Mean
      (SEM) ovarian stromal time averaged maximum velocity (TAMX) was 10.55 (0.91) and
      10.89 (1.80) cm/s in groups 2 and 3 respectively, both significantly greater than
      mean ovarian stromal TAMX of group 1, (P < 0.001). There was no significant
      difference in pulsatility index (PI) between the three groups. There thus appears
      to be significantly greater ovarian stromal blood flow velocity in women with
      polycystic ovaries as detected by colour and pulsed Doppler ultrasound. Increased
      ovarian stromal blood velocity may be a new parameter to assist in the ultrasound
      diagnosis of PCO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567829
TI  - Designer contraceptive pills.
AB  - The present world population of 5.6 billion is projected to reach 9 billion by
      the year 2025. Overpopulation remains one of the overwhelming issues of the 21st
      century, but only limited effort and resources have been allocated to designing
      new contraceptives, as evidenced by the diminished interest of the pharmaceutical
      industry and funding agencies. Major advances have been made recently in our
      understanding of the genetic basis of an individual's risk to various
      reproductive cancers and sex steroid-related diseases. It has also become
      apparent that agonistic and antagonistic analogues of sex steroids with tissue
      specific actions can be formulated. These new insights provide the opportunity to
      develop the next generation of 'designer' contraceptive pills with disease
      prevention benefits.

PMID- 8567830
TI  - Antiphospholipid antibodies and beta 2-glycoprotein-I in 500 women with recurrent
      miscarriage: results of a comprehensive screening approach.
AB  - Five hundred consecutive women (median age 33 years; range 19-45) with a history
      of recurrent miscarriage (median 4; range 3-16) were screened for the presence of
      antiphospholipid antibodies (APA)-lupus anticoagulant (LA) and/or anticardiolipin
      antibodies (ACA). The prevalence of persistently positive tests for LA was 9.6%
      and for immunoglobulin G (IgG) and immunoglobulin M (IgM) ACA was 3.3 and 2.2%
      respectively. Only seven women (1.4%) were LA and ACA positive. Repeat testing,
      after an interval of at least 8 weeks, demonstrated that only 65.7% of LA
      positive, 36.6% IgG ACA positive and 36.0% IgM ACA positive women on initial
      testing had a second positive test result. The dilute Russell's viper venom time
      detected the LA significantly more often than either the activated partial
      thromboplastin time or the kaolin clotting time (P < 0.001). There was no
      difference in the gestation of previous miscarriages between APA positive and APA
      negative women. There was no difference in the plasma beta 2-glycoprotein-I
      concentrations between APA positive and APA negative women with miscarriages and
      normal women. All women with a history of recurrent miscarriage should be tested
      for the presence of both LA and ACA. A second confirmatory test should be
      performed in those with an initial positive test result.

PMID- 8567831
TI  - Ovarian autoimmunity and corticotherapy in an in-vitro fertilization attempt.
AB  - This case report describes a successful pregnancy and delivery in a woman
      presenting with ovarian autoimmunity who had previously been involved in two
      unsuccessful in-vitro fertilization (IVF) attempts. Ten days before a third
      attempt, she began a regimen of 25 mg per day of prednisolone which was continued
      throughout the whole IVF protocol. Ovulation was induced by human menopausal
      gonadotrophin. After administration of 5000 IU of human chorionic gonadotrophin,
      18 oocytes were collected. At 48 h after insemination with the patient's
      husband's spermatozoa, four 4-cell pre-embryos were transferred. A singleton
      pregnancy developed and led to the birth of a girl who is doing well 10 months
      later.

PMID- 8567832
TI  - Do infertility tests discriminate between fertile and infertile populations?

PMID- 8567833
TI  - Inter-observer agreement in analysis of basal body temperature graphs from
      infertile women.
AB  - In this study, we evaluated the reproducibility of analysis of basal body
      temperature graphs under optimized conditions for agreement. A total of 160
      recordings were selected from spontaneous cycles of infertile women and analysed
      by three experienced clinicians using uniform criteria. Agreement at the various
      stages of analysis was assessed by the 'proportions of agreement' with 95%
      confidence intervals. Agreement in identification of the thermal nadir was
      clearly superior to that reported in previous publications. Reproducibility of
      'ovulatory' graph features (i.e. biphasic graphs and adequate thermal shifts) was
      excellent. Agreement in classification of monophasic graphs and inadequate
      thermal shifts, although lower, was still good. Thus, with experienced observers
      and uniform criteria, a good agreement can be achieved in analysis of the most
      important parameters of the basal body temperature graph. We believe that an
      effort should be made to generalize the use of uniform analysis criteria, because
      only then can results from different institutions be compared and the remaining
      clinical evaluation of the method be performed.

PMID- 8567834
TI  - Cancer and male infertility.
AB  - Male cancer and infertility are linked in three different ways. First, in certain
      malignancies, such as Hodgkin's disease, testicular and endocrine cancers,
      infertility may precede the diagnosis of cancer. The cause of infertility in
      these cases is not always obvious, although endocrine and immune aetiologies are
      responsible in some of them. Therefore, during evaluation of an infertile male,
      the possibility of cancer should be borne in mind. Second, cryptorchidism causes,
      in a parallel course, infertility and cancer. Third, improved survival of
      childhood and adolescent cancer is the trend of modern medicine. However,
      infertility is an important major sequela of treatments. The roles of
      chemotherapy, radiotherapy and surgery on fertility potential are stressed and
      possible treatment modalities in such cases are discussed.

PMID- 8567835
TI  - Gamete intra-Fallopian transfer or in-vitro fertilization after failed ovarian
      stimulation and intrauterine insemination in unexplained infertility?
AB  - A prospective randomized study was designed to compare gamete intra-Fallopian
      transfer (GIFT) and in-vitro fertilization (IVF) and embryo transfer in the
      treatment of couples who have failed to conceive after at least three cycles of
      ovarian stimulation and intrauterine insemination (IUI). A total of 69 couples
      with primary unexplained infertility of at least 2 years' duration plus at least
      three failed cycles of ovarian stimulation and IUI were randomly allocated to
      either GIFT or IVF/embryo transfer. The clinical pregnancy rate was 34% after
      GIFT treatment and 50% after IVF/embryo transfer. This difference was not
      statistically significant. The twin rate in the IVF/embryo transfer group was
      higher than in the GIFT group (53 versus 17%, P = 0.005). We conclude that
      patients with unexplained infertility and failed ovarian stimulation and IUI can
      still achieve encouraging pregnancy rates with IVF/embryo transfer or GIFT. Since
      IVF/embryo transfer is the least invasive of the two procedures and may yield
      diagnostic information, we would favour this therapy; however, the number of
      embryos transferred should be reduced to two to reduce the risk of twin
      pregnancy.

PMID- 8567836
TI  - Consistency and variation in fertility investigations in Europe.
AB  - A questionnaire survey among the teaching departments of obstetrics and
      gynaecology in Western Europe (response rate 71%) revealed only weak adherence to
      the World Health Organization recommendations for the standard investigation of
      the infertile couple. Both general and specific examinations were applied more
      frequently in the female than in the male partner. Although semen analysis and
      the ascertainment of ovulation were standard in virtually all departments, the
      criteria for normal semen and the methods used for the detection of ovulation
      varied greatly among both departments and countries. There were also large
      differences among countries in the preferred standard method for testing tubal
      patency. The data suggest that fertility investigations are based more on
      tradition and personal preferences than on the demonstrated utility of its
      components.

PMID- 8567837
TI  - The use of epididymal and testicular spermatozoa for intracytoplasmic sperm
      injection: the genetic implications for male infertility.
AB  - The results and rationale of using testicular and epididymal spermatozoa with
      intracytoplasmic sperm injection (ICSI) for severe cases of male infertility are
      reviewed. A total of 72 consecutive microsurgical epididymal sperm aspiration
      (MESA) cases were performed for congenital absence of the vas (CAV) and for
      irreparable obstructive azoospermia. ICSI was used to obtain normal embryos for
      transfer and fertilization in 90% of the cases. The overall fertilization rate
      was 46% with a normal cleavage rate of 68%. The pregnancy and delivery rates per
      transfer were 58 and 37% respectively. The delivery rate per cycle was 33%. In
      many cases, no epididymal spermatozoa were available and so testicular sperm
      extraction (TESE) was used for sperm retrieval. The transfer rate was lower with
      TESE (84 versus 96%) and the spermatozoa could not be frozen and saved for use in
      future cycles. However, there was little difference in pregnancy rates using
      epidiymal or testicular spermatozoa. The results were not affected by whether the
      obstruction was caused by CAV or failed vasoepididymostomy. Both fresh and frozen
      spermatozoa gave similar results; the only significant factor appeared to be the
      age of the female. Because of the consistently good results obtained using
      epididymal sperm with ICSI when compared with conventional IVF, and the similarly
      good results with testicular tissue spermatozoa, ICSI is mandatory for all future
      MESA patients. All CAV patients and their partners should be offered genetic
      screening for cystic fibrosis; hence pre-implantation embryo diagnosis should be
      available in any full service MESA programme. It is now clear that even with non
      obstructive azoospermia, e.g. Sertoli-cell only, or maturation arrest, there are
      usually some small foci of spermatogenesis which allow TESE with ICSI to be
      carried out. This means that even in men with azoospermia due to absence of
      spermatogenesis or to a block in meiosis, there are usually a few spermatozoa
      available in the testes that are adequate for successful ICSI. Finally, it is
      likely that some forms of severe male factor infertility are genetically
      transmitted and although ICSI offspring have been shown to be completely normal,
      it is possible that the sons of these infertile couples will also require ICSI
      when they grow up and wish to have a family.

PMID- 8567838
TI  - Laparoscopic tubal anastomosis (the one stitch technique): preliminary results.
AB  - We report a new laparoscopic technique of tubal anastomosis: the laparoscopic one
      stitch technique. After preparation and approximation of the two tubal segments,
      the anastomosis consists of one single suture placed at the '12 o'clock' site of
      the antimesenteric borders. Four patients have undergone this procedure.
      Bilateral tubal patency was confirmed in three cases. Hysterosalpingography was
      not performed on the fourth patient as she was already 1 month pregnant after
      tubal anastomosis.

PMID- 8567839
TI  - Ureteral injury during laparoscopically assisted radical vaginal hysterectomy.
AB  - We report on a case of ureteral injury during laparoscopically radical
      hysterectomy to treat a patient with a stage IA2 carcinoma of the uterine cervix.
      The advantage of laparoscopically radical hysterectomy is the prevention of the
      identification and dissecting of the ureter from a vaginal approach, the main
      problem in the Schauta technique. However, ureteral injury may still occur while
      resecting the cardinal ligament without good visualization of the ureter during a
      vaginal procedure. Because the ureter was well identified and freed
      laparoscopically, a vaginal approach after uterine removal may be an option for
      treatment. Moreover, using the ureteral stent as a marker during a modified
      Schauta technique is helpful in the prevention of ureteral injury during
      laparoscopically assisted radical vaginal hysterectomy.

PMID- 8567840
TI  - Donor insemination according to recent and strict guidelines--how safe can
      patients and doctors be?

PMID- 8567841
TI  - Acrosome reaction induced in a limited population of human spermatozoa by
      progesterone (Ca(2+)-dependent) and ATP (Ca(2+)-independent).
AB  - We examined the kinetics of the acrosome reaction induced in human spermatozoa by
      progesterone (Ca(2+)-dependent) and adenosine 5'-triphosphate (ATP; Ca(2+)
      independent). ATP and progesterone did not induce the acrosome reaction unless
      spermatozoa were incubated in a capacitation medium. ATP exhibited a constant
      induction of the acrosome reaction regardless of the incubation period, while
      progesterone began to induce the acrosome reaction after > or = 6 h of
      incubation. At 24 h of incubation, the percentages of spermatozoa in which the
      acrosome reaction had been induced by both progesterone and ATP were almost
      equal. To determine whether a limited population of human spermatozoa was
      reactive to both progesterone and ATP, we employed an MH61 bead binding method.
      When the acrosome-reacted spermatozoa were removed with MH61 beads, their
      percentage in the sperm suspension was decreased to < 3%. At 24 h of incubation,
      progesterone and ATP induced the acrosome reaction in 12.0 and 10.0% of
      spermatozoa, respectively. After MH61 bead binding was performed, the remaining
      spermatozoa did not react to the other activator (progesterone-->ATP, ATP-
      >progesterone). These findings indicate that only a limited population of human
      spermatozoa has the potential to undergo the acrosome reaction when stimulated by
      both progesterone and ATP.

PMID- 8567842
TI  - Effectiveness of various sperm processing methods in removing seminal plasma from
      insemination media.
AB  - The effectiveness of the wash and swim-up (1 and 2 wash cycle), two layer Percoll
      gradient, SpermPrep and underlay sperm preparation methods in removing seminal
      plasma from insemination suspensions was investigated. The number of wash cycles
      needed to rid sperm suspensions of seminal plasma (n = 15) was also determined.
      All sperm preparation methods were compared to the control wash and swim-up
      method, performed using Earle's buffered salt solution (EBSS), without serum
      supplementation so as not to mask seminal plasma concentrations. Control
      processing comprised 1 ml semen subjected to two wash cycles in EBSS followed by
      a swim-up period of 60 min under 5% CO2 in air. The Percoll method comprised 1 ml
      semen layered on a discontinuous 36 and 81% Percoll gradient (n = 14). In the
      SpermPrep method, 1 ml semen was run through a SpermPrep II column (n = 10), and
      underlay samples (n = 12) were processed by two wash cycles, after which sperm
      pellets were resuspended in the remaining medium, layered under 1.2 ml EBSS and
      allowed to swim up under 5% CO2 in air for 1 h. Seminal plasma and supernatant
      fractions obtained after each processing phase were stored at -20 degrees C and
      protein concentrations were determined by spectrophotometry. The wash and swim-up
      method was the most effective in removing seminal plasma from sperm suspensions,
      followed by the two-layer Percoll gradient, underlay and finally the SpermPrep II
      processing methods.

PMID- 8567843
TI  - Analysis of sperm movement in relation to the oxidative stress created by
      leukocytes in washed sperm preparations and seminal plasma.
AB  - The addition of luminol to unprocessed semen samples resulted in the generation
      of chemiluminescent signals, the intensity of which was highly correlated with
      the level of leukocyte contamination. Despite the spontaneous oxidant-generating
      capacity of seminal leukocytes, no correlations were observed between leukocyte
      contamination and the fertility status of the subjects or any aspect of the semen
      profile, including the motility of the spermatozoa or their performance in a
      hyaluronate penetration assay. Luminol-dependent chemiluminescence and leukocyte
      contamination were also correlated in washed sperm suspensions prepared either by
      repeated centrifugation or on discontinuous Percoll gradients. However, in such
      sperm suspensions, the spontaneous generation of oxidants by contaminating
      leukocytes (> 2 x 10(4) leukocytes/ml) was invariably associated with a decreased
      capacity for movement. Moreover, causative associations between leukocyte
      contamination, reactive oxygen species generation, lipid peroxidation and
      impaired sperm motility were revealed by experiments involving the selective
      addition or removal of activated leukocytes. From these observations we can
      conclude that low concentrations of leukocytes are a common feature of the human
      ejaculate and can impair sperm function, particularly in the absence of seminal
      plasma. These findings have implications for our understanding of the importance
      of leukocytospermia in defining the fertility of human spermatozoa in vivo and in
      vitro.

PMID- 8567844
TI  - Effectiveness of long-acting gonadotrophin-releasing hormone agonist treatment in
      combination with conventional therapy on testicular outcome in human
      orchitis/epididymo-orchitis.
AB  - A group of 24 patients suffering from acute post-pubertal orchitis/epididymo
      orchitis were prospectively randomized to treatment over a total period of 3
      months with a combined conventional plus long-acting gonadotrophin-releasing
      hormone analogue (GnRHa) (leuprolide, 3.75 mg every 27 days) therapy (n = 13,
      group A) or conventional therapy alone (n = 11, group B) respectively, in order
      to verify any differences in clinical and sperm outcome during treatment and
      follow-up. Seven patients affected by uncomplicated mumps (group C), receiving
      GnRHa for 3 months, served as an additional control group. Combined leuprolide
      plus conventional therapy provided better outcomes than conventional therapy
      alone in terms of scrotal ultrasound scans and serum antisperm antibodies (ASA)
      at time of presentation and monthly thereafter throughout the study: the most
      solid data relate to testicular atrophy in three out of 11 patients from group B
      and their sAb positivity persisting, as opposed to zero out of 13 in group A.
      Moreover, semen analyses performed at 3-6 months after therapy withdrawal
      revealed in groups A and C mean total sperm counts and percentages of oval forms
      significantly higher than those observed in group B. It is concluded that GnRHa
      treatment is a promising pharmacological tool with no side-effects, effective in
      reducing testicular vascular leakages in male orchitis.

PMID- 8567845
TI  - Modulation of prostaglandin synthesis in mammalian sperm acrosome reaction.
AB  - Exogenous arachidonic acid induces the acrosome reaction and the production of
      the prostaglandins PGE2 and PGF2 alpha in bovine spermatozoa. Exogenous PGE2 also
      induces the acrosome reaction and PGF2 alpha synthesis. To understand better the
      role of PGE2 in the induction of PGF2 alpha synthesis through modulation of
      phospholipase A2, inhibitors of this enzyme were used. The effects of PGE2 were
      blocked by phospholipase A2 inhibitors and this inhibition was reversed by
      addition of arachidonic acid. These data indicate that PGE2 activates
      phospholipase A2 to produce arachidonic acid. To determine whether protein kinase
      C modulates phospholipase A2 activity in this process, staurosporin, an inhibitor
      of protein kinase C, was used. The effect of PGE2 on PGF2 alpha production is
      inhibited by staurosporin and this inhibition was reversed by addition of
      arachidonic acid indicating that protein kinase C is involved in phospholipase A2
      activation. The effect of exogenous arachidonic acid or PGE2 on the acrosome
      reaction is blocked by lipoxygenase inhibitors but not by inhibitors of cyclo
      oxygenase, indicating that lipoxygenase products are involved in the mechanism of
      the acrosome reaction. The presented data shed light on the cross-talk between
      cyclo-oxygenase and lipoxygenase and their involvement in the sperm acrosome
      reaction. It is suggested that cyclo-oxygenase products modulate the activity of
      lipoxygenase which is a key enzyme in the mechanism leading to the acrosome
      reaction. Stimulation of cyclo-oxygenase to synthesize PGE2 activates
      phospholipase A2 to release arachidonic acid which is the substrate for
      lipoxygenase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567846
TI  - Variations in spontaneous and induced acrosome reaction: correlations with semen
      parameters and in-vitro fertilization results.
AB  - To determine whether variations in spontaneous and induced acrosome reactions are
      correlated with semen quality, and to identify the inducers of clinical interest,
      the acrosome reaction, sperm concentration, motility and morphology were recorded
      in 117 semen samples from patients undergoing an in-vitro fertilization (IVF)
      attempt. The spontaneous acrosome loss after 24 h incubation in Menezo B2 medium
      and after induction by calcium ionophore A23187, progesterone, human follicular
      fluid, cyclic adenosine 3'-5'-phosphate (cAMP) analogue and phorbol ester (TPA)
      were measured using the fluorescein isothiocyanate-GB24 antibody. The mean
      (range) spontaneous acrosome reaction was 3.4 +/- 0.6% (0.0-30.0). Response to
      the tested inducers was 23.3 +/- 1.6% (0.0-72.0) for calcium ionophore, 5.4 +/-
      0.8% (0.0-60.0) for progesterone, 1.0 +/- 0.7% (0.0-24.0) for human follicular
      fluid, 2.6 +/- 0.7% (0.0-39.0) for the cAMP analogue and 2.3 +/- 0.7% (0.0-31.0)
      for TPA. The response to calcium ionophore was correlated significantly to sperm
      concentration, motility and morphology, while the responses to progesterone and
      TPA were correlated significantly to motility and acrosome morphology. The
      responses to other inducers were not linked to classic semen parameters. When
      studying acrosome reaction as a function of IVF results, the responses to calcium
      ionophore and TPA were discriminant. The results of this study show that the
      spontaneous acrosome loss and the responses to acrosome reaction inducers are
      highly variable and partially linked to semen quality. The responses to calcium
      ionophore and TPA could be of interest in predicting the fertilizing ability in
      vitro.

PMID- 8567847
TI  - Evaluation of a computer-aided semen analysis system with sperm tail detection.
AB  - The aim of this study was to evaluate the Stroemberg-Mika cell motion analyser
      (SM-CMA) which uses tail detection in order to discriminate between immotile
      spermatozoa and other particles. Analysis of the spermatozoa by the SM-CMA can
      easily be checked on a video monitor. The semen samples were from donors and
      patients visiting the fertility unit of the University Hospital, Hanzeplein, The
      Netherlands. Both fresh semen samples and purified sperm suspensions were used to
      estimate sperm counts and motility characteristics. We tested the use of the x10
      objective instead of the x20 and we assessed the ways in which motility
      characteristics were influenced by temperature. We found a considerable
      discrepancy between sperm concentrations measured manually and by computerized
      analysis, both in semen samples and in purified sperm suspensions. The SM-CMA
      correctly recognizes motile spermatozoa, but underestimates immotile ones.
      Although temperature affects motility characteristics, in routine measurements
      the influence of short cooling periods, which are unavoidable, was nil. We found
      that using the x10 objective can be useful, especially at low sperm
      concentrations. In our opinion, the SM-CMA system is, despite some shortcomings
      in its user-interface, a useful and versatile instrument for examination of human
      semen samples, with desirable features.

PMID- 8567848
TI  - Implementing comprehensive quality control in the andrology laboratory.
AB  - Comprehensive quality control procedures were integrated into the routine semen
      analysis workload of a large university-based andrology laboratory. Methods were
      chosen to match as far as possible those which have been used successfully for
      many years in disciplines such as clinical chemistry. Levey-Jennings and cusum
      charts were plotted in order to monitor the immunobead-binding test for antisperm
      antibodies and a video-taped control sample for computerized semen analysis. A
      cryopreserved semen control was also charted. Daily manual sperm counts were
      plotted against the corresponding computer-assisted semen analysis (CASA) value.
      Multiple readings of 30 slides were used to monitor morphology assessments.
      Monthly means for morphology were also calculated regularly. Coefficients of
      variation were calculated for all variables and were found to be more appropriate
      for some aspects, such as CASA, than for others, such as morphology, when
      difference from the previous reading of the same slide was found to be more
      useful. These integrated quality control procedures had a direct influence on the
      production of results from the laboratory. Together with a high standard of
      technician training, comprehensive routine quality control based on repeated
      analyses of control samples is an effective way of assuring the validity of semen
      analysis results.

PMID- 8567849
TI  - Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients.
AB  - The criteria for the diagnosis of the polycystic ovary syndrome (PCOS) have still
      not been agreed universally. A population of 1741 women with PCOS were studied,
      all of whom had polycystic ovaries seen by ultrasound scan. The frequency
      distributions of the serum concentrations of follicle stimulating hormone (FSH),
      luteinizing hormone (LH), testosterone and prolactin and the body mass index,
      ovarian volume, uterine cross-sectional area and endometrial thickness were
      determined and compared with the symptoms and signs of PCOS. Obesity was
      associated with hirsutism and an elevated serum testosterone concentration and
      was also correlated with increased rates of infertility and cycle disturbance.
      The rates of infertility and cycle disturbance also increased with serum LH
      concentrations > 10 IU/l. A rising serum concentration of testosterone [mean and
      95th percentiles 2.6 (1.1-4.8) nmol/l] was associated with an increased risk of
      hirsutism, infertility and cycle disturbance. The ovarian volume was correlated
      with serum concentrations of testosterone, LH and the body mass index, which was
      also correlated with the uterine area. This descriptive data from the largest
      reported series of women with PCOS enables the development of a management
      orientated approach to the syndrome. Women who are overweight can expect an
      improvement in their symptoms if they lose weight. An elevated concentration of
      LH (> 10 IU/l) is associated with infertility and treatment should be chosen
      accordingly. If the serum testosterone concentration is > 4.8 nmol/l, other
      causes of hyperandrogenism should be excluded.

PMID- 8567850
TI  - Pregnancy and birth after intracytoplasmic sperm injection with spermatozoa from
      a patient with tail stump syndrome.
AB  - Tail stump syndrome, which may be associated with primary ciliary dyskinesia, is
      also associated with morphological defects of the flagellum resulting in severe
      asthenozoospermia. Until recently, these morphological anomalies caused definite
      male infertility. Today, however, new methods such as micromanipulation
      techniques provide a rational therapy for this patient group. A pregnancy
      followed by living offspring was achieved following the intracytoplasmic
      injection of immotile spermatozoa from a patient with tail stump syndrome.

PMID- 8567851
TI  - Immunolocalization of transforming growth factor-beta 1 and transforming growth
      factor-beta 2 in the mouse ovary during gonadotrophin-induced follicular
      maturation.
AB  - An immunohistochemical approach was utilized to evaluate the cellular
      distribution of transforming growth factor-beta 1 (TGF beta 1) and transforming
      growth factor beta 2 (TGF beta 2) at different stages of follicle development in
      the prepubertal mouse ovary under the following conditions: (i) after pregnant
      mare's serum gonadotrophin (PMSG) treatment; (ii) after PMSG and human chorionic
      gonadotrophin (HCG) treatment; (iii) after PMSG and HCG treatment plus mating. In
      the immature ovary, TGF beta 1 and TGF beta 2 immunoreactivities are localized in
      theca and granulosa cells and in oocytes. After PMSG treatment, TGF beta 1 and
      TGF beta 2 immunoreactivities are localized in granulosa cells; in addition, TGF
      beta 2 staining is noted in the matrix surrounding antral cells. Staining for
      both TGR beta 1 and TGF beta 2 drops in the theca but persists in the oocyte.
      PMSG plus HCG treatment results in a significant increase in TGF beta 1 and TGF
      beta 2 immunoreactivity in the theca and in the maintenance of TGF beta 1
      staining in both basal granulosa cells and cumulus cells whereas TGF beta 2
      immunoreactivity is essentially localized in the matrix surrounding cumulus
      cells. Staining for TGF beta 1 and TGF beta 2 persists in the oocyte. Following
      PMSG plus HCG treatment and mating, TGF beta 1 immunoreactivity is localized in
      the luteal cells of corpora lutea and TGF beta 2 shows a similar localization
      pattern. This study provides evidence that TGF beta 1 and TGF beta 2 peptides are
      expressed in specific cell types during induced follicular maturation in the
      mouse ovary.

PMID- 8567852
TI  - Follistatin concentrations in follicular fluid of normal and polycystic ovaries.
AB  - Follistatin (FS) is an activin/inhibin binding protein which is believed to act
      in an autocrine/paracrine manner to regulate growth and differentiation. Although
      FS has been identified in human follicular fluid, it remains unclear how its
      concentration changes during selection and atresia, and what the concentrations
      of FS are in follicles of women with polycystic ovary syndrome (PCOS). Towards
      this goal, we have measured by radioimmunoassay the concentrations of FS in
      follicular fluid obtained from dominant and atretic cohort follicles of normal
      cycling women, preovulatory follicles of in-vitro fertilization (IVF) patients,
      and small Graafian follicles of patients with PCOS. In all cases, the follicular
      fluid concentration of FS was much higher (approximately 100-fold) than that
      reported in serum. The FS concentrations (ng/ml) were 203 +/- 42 (normal
      dominant), 185 +/- 17 (atretic cohort), 185 +/- 5 (IVF), and 250 +/- 14 (PCOS).
      There was no statistical difference between these mean values of FS. Further,
      there were no significant correlations between the follicular fluid
      concentrations of FS and the concentrations of oestradiol, progesterone, or
      androstenedione. These results indicate that human Graafian follicles, regardless
      of whether they are healthy or atretic, normal or PCOS, contain high steady-state
      concentrations of FS in the micro-environment. Collectively, these data fit with
      the hypothesis that major increases and decreases in the concentration of FS in
      the micro-environment may not play a key role in the mechanisms of selection,
      atresia, and PCOS in women. The possibility of regulation of intrinsic activin
      and inhibin activity through FS binding is discussed.

PMID- 8567853
TI  - Normal development and metabolic activity of preimplantation embryos in vitro
      from patients with polycystic ovaries.
AB  - Polycystic ovary syndrome (PCOS) is closely associated with high miscarriage
      rates and, following in-vitro fertilization (IVF), with decreased fertilization
      rates, suggesting that oocytes and embryos are of poor quality. In this
      prospective study, we examined the development, metabolic activity and blastocyst
      cell number of embryos following IVF from 51 patients with either anovulatory
      PCOS, ovulatory PCOS or tubal disease. The number of oocytes retrieved and the
      fertilization rates were similar for patients with PCOS and tubal disease.
      Following embryo transfer, 46% of the patients with PCOS and 36% of patients with
      tubal disease became pregnant. A similar proportion of surplus embryos from
      patients with PCOS and tubal disease developed to the blastocyst stage (38% and
      43% respectively). Patients with anovulatory PCOS had embryos with less
      fragmentation which cleaved faster, cavitated earlier and had more cells at the
      blastocyst stage than embryos from patients with tubal disease. While the profile
      of glucose uptake and lactate production was similar for all groups throughout
      preimplantation development, patients with tubal disease who underwent ovulation
      induction using the 'titrated' regimen optimized for PCOS patients resulted in
      embryos with reduced pyruvate uptake, in addition to low blastocyst cell numbers.
      This study demonstrates that with an optimized ovulation induction regimen,
      embryos from PCOS patients are of good quality and developmental potential.

PMID- 8567854
TI  - Cryopreservation: the problem of evaluation.
AB  - A simple evaluatory formula for reporting pregnancy rates involving cryopreserved
      material has so far remained elusive. It is highly desirable to have a method
      which would allow not only an evaluation of cryotechnology per se, but also an
      evaluation of the role of cryotechnology in enhancing the total reproductive
      potential of a single cycle. In this paper, nine separate formulae are described
      which can be used for the evaluation of cryopreservation. It is concluded that
      none of the existing formulae used alone expresses the total potential of
      cryopreservation, and that while each formula provides information regarding some
      aspect of the role of cryopreservation, the most comprehensive evaluation
      requires the answer to five different equations. The other four formulae, while
      often used, are regarded as providing information which is unsubstantiated or
      does not allow complete evaluation.

PMID- 8567855
TI  - Increase in the rate of diploidy with maternal age in unfertilized in-vitro
      fertilization oocytes.
AB  - Human oocytes which failed to fertilize in vitro were fixed for cytogenetic
      analysis. Metaphase II chromosomes were identified in 286 oocytes, of which 233
      were suitable for cytogenetic analysis. In all, 181 oocytes had a normal haploid
      karyotype (77.7%), while the remaining 52 were abnormal (28 aneuploid, 14 diploid
      and 10 tetraploid). The rate of aneuploidy did not increase with maternal age.
      However, the proportion of diploid oocytes increased significantly with advancing
      maternal age (P < 0.01), being particularly obvious in women aged > 35 years.

PMID- 8567856
TI  - The isolation, characterization and culture of human decidual endothelium.
AB  - A novel method has been developed for the isolation of microvascular endothelium
      from first trimester decidua. Enzymatic dispersion and Percoll gradient
      centrifugation, followed by positive selection using Ulex europaeus coated
      immunomagnetic beads, yields pure isolates of endothelium. Typical 'cobblestone'
      monolayers form within 3-5 days; cells express the classical endothelial markers
      CD31 and Von Willebrand factor and the inducible cell adhesion molecules
      endothelial-leukocyte adhesion molecule and vascular cell adhesion molecule. Cell
      growth is dependent on both high concentrations of magnesium ions and human
      serum. Of the endothelial growth factors examined, only vascular endothelial
      growth factor stimulated growth, suggesting an important role for this factor in
      uterine angiogenesis.

PMID- 8567857
TI  - Endometrial and placental protein markers and ovarian steroids in serum during in
      vitro fertilization cycles.
AB  - The objective of this study was to find the earliest time at which it was
      possible to detect clinical pregnancy in an in-vitro fertilization (IVF)
      treatment cycle supported with human chorionic gonadotrophin (HCG), and also
      retrospectively to diagnose abnormal ovarian- or endometrium-related situations
      in failure cycles. Serum samples were taken in 41 IVF cycles at frequent
      intervals from the beginning of ovarian stimulation until menstrual bleeding
      occurred or a pregnancy was established. Concentrations of oestradiol,
      progesterone, placental protein 14 (PP14), pregnancy-specific beta 1-glycoprotein
      (SP1), and pregnancy-associated plasma protein A (PAPP-A) were determined in the
      serum samples using commercially available (steroid) or purpose-developed
      (protein) immunoassays. The cycles were retrospectively distributed into four
      outcome groups: (i) fertilization failure (FF, n = 8); (ii) implantation failure
      (IF, n = 10); (iii) 'interaction' (embryo-endometrium) cycle (IC, n = 14), and
      (iv) clinical pregnancy (CP, n = 9). The embryo-endometrium interaction was
      detected by a rise in SP1 in 23 cycles (70% of embryo transfers) at a time when
      endogenous HCG was still masked by external support. Early ('false') positive SP1
      concentrations were observed in two out of eight and five out of 14 cases in
      groups FF and IC respectively, but never amongst the ongoing pregnancies (CP).
      PAPP-A did not distinguish pregnancy from the other outcomes. The
      PP14/progesterone ratio was lower, later in the cycle, in CP than in the other
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567858
TI  - Two instead of three embryo transfer in in-vitro fertilization.
AB  - The rational of transferring two instead of three embryos was studied through 468
      in-vitro fertilization (IVF) treatment cycles in 287 couples. The quality of 1224
      embryos was determined according to the fragmentation rate and the morphology as
      good (A) and poor (B). The influence of the number of embryos transferred (two or
      three) on the pregnancy rate when the same quality or combinations of good and
      poor quality embryos transferred was examined. When only good quality embryos
      were transferred the pregnancy rates in double (AA) and triple (AAA) embryo
      transfer were 40.5 (17/42) and 42.9% (30/70) respectively (not significant). When
      only poor quality embryos were transferred, the pregnancy rates in double (BB)
      and triple (BBB) embryo transfers were 11.0% (11/100) and 22.9% (16/70)
      respectively (P < 0.001). On the other hand, when good and poor quality embryos
      were transferred together as AB in double and as AAB and ABB in triple embryo
      transfer, the pregnancy rates were 36.8 (14/38) and 39.9% (59/148) respectively
      (not significant). There was no difference in the miscarriage rate between double
      and triple embryo transfers; 16.7 and 18.1% respectively. The multiple pregnancy
      rate was 14.3% for double embryo transfers and 32.4% for triple embryo transfers
      (P < 0.001). This study demonstrates that if there is at least one good quality
      embryo available for transfer, then double instead of triple embryo transfer will
      not yield a significantly lower pregnancy rate. The influence of the number of
      embryos transferred on the pregnancy rate became significant when only poor
      quality embryos were transferred.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8567859
TI  - Human chorionic gonadotrophin release and tissue viability in placental organ
      culture.
AB  - The use of human chorionic gonadotrophin (HCG) secretion as a measure of
      viability during the organ culture of human first trimester placental tissue has
      become a popular practice. It has been suggested that if cultured tissue is
      releasing large amounts of this protein hormone, there is a high level of
      viability. We have found, however, that the cytosolic enzyme L-lactate
      dehydrogenase is released into the culture supernatant in a similar daily pattern
      as HCG, suggesting that tissue disruption may be occurring, resulting in some of
      the observed hormone release. In addition, we have shown that the uptake of the
      fluorescent dye dansyl-L-lysine into the syncytium increases significantly from
      day 0 to day 4, suggesting a loss of syncytial membrane integrity. Electron
      micrographs show further evidence of the syncytial degeneration at the
      ultrastructural level, displaying extensive vacuolation and poor microvillous
      cover. In contrast to the degenerated state of the syncytiotrophoblast, a high
      level of bromodeoxyuridine incorporation is observed for cytotrophoblasts and, in
      particular, stromal cells up to 5 days in culture. Overall, the results suggest
      that the use of HCG release as a determinant of tissue viability in placental
      organ culture should be treated with a degree of caution.

PMID- 8567860
TI  - The prediction of ectopic pregnancy after in-vitro fertilization and embryo
      transfer.
AB  - Data from 135 patients who suffered ectopic pregnancies and from 135 patients who
      progressed to singleton deliveries after in-vitro fertilization and embryo
      transfer have been analysed retrospectively. The ectopic pregnancies represent
      all such cases observed at Bourn Hall Clinic between 1983 and 1993. The delivered
      group was randomly selected from the same time period. The ectopic pregnancies
      included 20 heterotopic, eight ovarian and six bilateral tubal pregnancies; the
      remainder were singleton tubal pregnancies. The aim of this study was to identify
      the variables which differed systematically for the two groups of patients and to
      explore whether such variables could be used to predict ectopic pregnancy at an
      early stage. The mean plasma concentration of human chorionic gonadotrophin and
      progesterone for the ectopic pregnancy group was significantly lower than that
      for the singleton delivery group (P < 0.001). However, there was such a degree of
      overlap that it was impossible to devise a cut-off concentration for either
      hormone which would offer a clinically useful predictor of ectopic pregnancy.
      Nevertheless, using the discriminant function analysis of these data, together
      with the history of pelvic inflammatory disease, we could predict up to 90% of
      cases of ectopic pregnancy by day 23 after embryo transfer, long before
      ultrasound imaging would be useful.

PMID- 8567861
TI  - Trizygotic quadruplet pregnancy following in-vitro fertilization: an additional
      factor against replacement of three embryos in young patients?
AB  - A study of a 25 year old woman with a previous history of tubal damage, ectopic
      pregnancy and unsuccessful tubal surgery is reported. Following in-vitro
      fertilization (IVF) treatment, four viable fetuses were revealed by ultrasound
      scan at 10 weeks gestation. Two shared the same gestational sac, thus
      establishing a trizygotic quadruplet pregnancy. The implications of monozygotic
      twinning in humans are discussed. It is concluded that embryo splitting and its
      consequences should be seriously considered when multiple embryo transfer in
      young patients is contemplated.

PMID- 8567862
TI  - Endoscopic management of a case of 'complete septate uterus with unilateral
      haematometra'.
AB  - Endoscopy and ultrasound was used to diagnose a 13 year old virgin girl who
      presented with dysmenorrhoea and suspected right side adnexal tumescence. The
      girl was found to have a complete septate uterus with non-communicating right
      hemicavity and haematometra, an exceptional type of Mullerian anomaly. After
      pretreatment with buserelin, hysteroscopic metroplasty was successfully
      performed.

PMID- 8567863
TI  - Tamoxifen treatment and its consequences.

PMID- 8567864
TI  - Tamoxifen treatment and its consequences.

PMID- 8567865
TI  - Multiple follicular development associated with a herbal medicine.

PMID- 8567866
TI  - Artificial insemination in RhD negative women.

PMID- 8567867
TI  - Timing of intercourse.

PMID- 8567868
TI  - Potential effects of Omeprazole in pregnancy.

PMID- 8567869
TI  - Evolution of the sperm aster after microinjection of isolated human sperm
      centrosomes into meiotically mature human oocytes.
AB  - This study examined the feasibility of isolating and transferring the centrosome
      containing region of spermatozoa to mature human oocytes. The findings
      demonstrate that individual sperm centrosomes can be transferred and are capable
      of nucleating maternal tubulin to form a well-developed sperm aster in the
      recipient oocyte. The results are discussed with respect to centrosome function
      in early human development and applications in clinical in-vitro fertilization in
      the treatment of certain forms of male factor infertility.

PMID- 8567870
TI  - The thiol reagent, thimerosal induces intracellular calcium oscillations in
      mature human oocytes.
AB  - The aim of this study was to investigate the effects of thimerosal on
      intracellular calcium in human oocytes related to the stage of nuclear maturity.
      A total of 20 oocytes from superovulated women undergoing gamete intra-Fallopian
      transfer (GIFT) were studied. The calcium-sensitive fluorescent dye Fura-2 was
      used to monitor intracellular calcium. Regular oscillations in the concentration
      of cytosolic calcium were observed in 13 out of 20 oocytes following exposure to
      thimerosal; five oocytes did not respond to thimerosal treatment, and spontaneous
      oscillations of cytosolic free calcium were recorded in two oocytes. Thimerosal
      induced oscillations of intracellular calcium in a significantly higher
      proportion of metaphase II oocytes (10/11) compared with metaphase I oocytes
      (3/8; P < 0.2). These findings demonstrate that thimerosal is a potentially
      useful agent for the study of the calcium signalling processes in human eggs and
      suggest that the underlying cellular mechanisms develop at a relatively late
      stage of oocyte maturation.

PMID- 8567871
TI  - PCR-amplified vitronectin mRNA localizes in situ to spermatocytes and round
      spermatids in the human testis.
AB  - Vitronectin is an adhesion protein present within the acrosomal cap region of
      human spermatozoa and is liberated during the acrosome reaction. The purpose of
      this study was to determine if vitronectin mRNA was synthesized in the male
      genital tract using the reverse transcriptase in-situ polymerase chain reaction
      (PCR) technique. Twelve genital tract tissues, which included six testes, one
      showing Sertoli cells only and one from a 3 year old boy, as well as sections
      from the prostate, seminal vesicles, and epididymis, were analysed for
      vitronectin transcripts. PCR-amplified vitronectin cDNA was detected in the
      seminiferous tubules of the four adult testes that showed normal spermatogenesis
      and localized to the spermatocytes and round spermatids. PCR-amplified
      vitronectin cDNA was not detected in the tissues of the prostate, epididymis, and
      seminal vesicles from the men whose testes did contain the message, nor in the
      testes with Sertoli cells only or that of the prepubertal boy. It is concluded
      that, in the male genital tract, vitronectin is transcribed exclusively in the
      germ cells at the spermatocyte and round spermatid stages. This demonstrates that
      the translated protein present in the spermatozoon is being produced in situ.
      Further study is needed to determine the role of this protein in the dynamics of
      sperm-oocyte interaction.

PMID- 8567872
TI  - Sperm motility inhibitor from human seminal plasma: association with semen
      coagulum.
AB  - Human seminal plasma contains a sperm motility inhibitor (SPMI) originating from
      the seminal vesicles as a 52 kDa precursor form that is rapidly degraded by
      prostatic proteases after ejaculation. In this study, the distribution of SPMI
      biological activity and antigens was analysed in chemically induced, as well as
      naturally occurring, arrest of semen liquefaction. SPMI activity was detected
      exclusively in the coagulated semen fraction at 2200 +/- 560 IU, whereas total
      seminal plasma proteins separated more evenly between soluble and coagulated
      components (91 +/- 19 and 65 +/- 18 mg, respectively). An SPMI antiserum
      recognized different forms of SPMI precursors at 52, 38, 35, 33 and 20 kDa in the
      coagulum while the soluble protein fraction contained only one major
      immunoreactive band at 15 kDa. High levels of SPMI activity (1500 +/- 180 IU/ml)
      together with high molecular mass forms of SPMI precursor and low sperm motility
      (26%) were detected in semen samples that failed to liquefy spontaneously at room
      temperature. Addition of prostatic secretions to the non-liquefying samples
      caused a decrease of SPMI activity (330 +/- 17 IU/ml) and transformed the SPMI
      precursor into low molecular mass forms (14-22 kDa) with a concomitant increase
      in sperm motility to 49%. The results suggest that SPMI is highly associated with
      the seminal coagulum components as very active forms that may adversely affect
      sperm motility when not properly processed after ejaculation.

PMID- 8567873
TI  - Macrophage and granulosa interleukin-1 beta mRNA in human ovulatory follicles.
AB  - Interleukin-1 beta (IL-1 beta) may be active in the ovary at ovulation and may be
      produced by immune and non-immune cells. This study evaluates the production of
      IL-1 beta by granulosa cells and macrophages from the human ovulatory follicle.
      The concentrations of IL-1 beta and IL-1 beta mRNA were measured in follicular
      aspirates taken from patients undergoing in-vitro fertilization and in cultures
      of cells from aspirates. Macrophages were detected by immunocytochemistry and by
      the reverse transcriptase polymerase chain reaction (RT-PCR). The macrophages
      were removed from granulosa cell preparations immediately or after the cells have
      been cultured for 24 h. IL-1 beta was detected by radioimmunoassay and
      transcripts were detected by RT-PCR and by in-situ hybridization on cytospun
      preparations using a [35S]IL-1 beta riboprobe. IL-1 beta and IL-1 beta mRNA were
      found in follicular aspirates, in granulosa luteal cell preparations containing
      macrophages and in highly purified granulosa cell preparations after removal of
      macrophages by all the methods used. Both macrophages and granulosa cells
      contained high concentrations of IL-1 beta transcripts. Moreover, the number of
      IL-1 beta reactive cells in granulosa cell preparations cultured for 24 h with 10
      15% macrophages before removal was twice that of granulosa cells cultured without
      macrophages. Thus, both granulosa cells and macrophages are actively involved in
      the ovarian production of IL-1 beta at ovulation and the ability of granulosa
      cells to produce IL-1 beta may require ovarian macrophages.

PMID- 8567874
TI  - Endothelin synthesis and receptors in human endometrium throughout the normal
      menstrual cycle.
AB  - This study was undertaken to investigate the presence of messenger RNA (mRNA) for
      prepro-endothelin-I (ET-1) and the known receptor subtypes (ETA and ETB) in human
      endometrium at different stages of the menstrual cycle obtained at hysterectomy.
      Northern blot analysis revealed expression of ET-1 mRNA in human endometrium
      during the normal menstrual cycle. The concentration of ET-1 mRNA in endometrial
      tissue was greater during the menstrual and proliferative phases than during the
      ovulatory and secretory phases. Immunoreactive ET-1 was secreted into the medium
      of isolated endometrial stromal cells. Oestradiol and progesterone significantly
      attenuated ET-1 release in endometrial stromal cells cultured for 6 days. ETA and
      ETB mRNA were also present in endometrial tissue of the normal cycle. The
      concentration of ETA receptor mRNA was greater in the proliferative phase than in
      the secretory phase, whereas expression of ETB mRNA increased in menstrual phase.
      ET-1 significantly increased extracellular accumulation of cyclic AMP (cAMP),
      intracellular generation of inositol phosphates and significantly enhanced DNA
      synthesis in cultured endometrial stromal cells from the proliferative phase. Our
      results showed that human endometrial cells synthesized and released ET-1, and
      contained ETA and ETB receptors which were functionally coupled to
      phosphoinositide breakdown and to adenylate cyclase with the increase of cAMP by
      ET-1 stimulation. Our findings suggest that ET-1 may have a potential autocrine
      and/or paracrine function in human endometrial stromal cells.

PMID- 8567875
TI  - In-vitro decondensation of human spermatozoa for fluorescence in-situ
      hybridization.
AB  - In order to enhance the efficiency of fluorescence in-situ hybridization (FISH)
      on human interphase spermatozoa, a simple method for partial decondensation of
      human spermatozoa chromatin is described. The spermatozoa were washed once in
      0.01 M Tris and decondensed using 10 mM dithiothreitol in 0.05 M Tris for 10-50
      min, before being spread onto clean slides. Sperm samples were observed every 10
      min under a phase-contrast microscope in order to modify the duration of the
      decondensation process. Using several centromeric or YAC probes in multicolour
      FISH, high hybridization rates were obtained.

PMID- 8567876
TI  - Simultaneous amplification of the two most frequent mutations of infantile Tay
      Sachs disease in single blastomeres.
AB  - Tay-Sachs disease is a lysosomal storage disease, which in its most severe form
      leads inexorably to death during infancy. We have developed a method for
      preimplantation diagnosis, using polymerase chain reaction (PCR) technology, by
      which the two most frequent mutations occurring in this disease can be amplified
      simultaneously. We have tested this method on single blastomeres and have
      compared four lysis methods: (i) boiling in water at 94 degrees C for 15 or (ii)
      30 min, and (iii) incubation in an alkaline lysis buffer for 30 min at 94 degrees
      C or (iv) at 65 degrees C for 10 min. The amplification percentages were 21, 67,
      71 and 91% respectively.

PMID- 8567877
TI  - Controlled clinical comparison of Isolator and BACTEC 9240 Aerobic/F resin bottle
      for detection of bloodstream infections.
AB  - A controlled clinical comparison was carried out with the BACTEC 9240 Aerobic/F
      resin bottle and the Isolator system with adult patients suspected of having
      bloodstream infections. A total of 10,500 paired specimens were collected, of
      which 1,122 from 520 patients were positive. There were 68 false-positive BACTEC
      bottles; 259 positive cultures that were excluded from analysis because the
      bottle, the Isolator, or both failed to meet the minimum volume criterion of 8 ml
      of blood; and 207 positive cultures that were excluded because the isolates were
      found to be clinically insignificant or of indeterminate clinical significance on
      the basis of patient assessment. A total of 656 positive cultures from 258
      patients formed the basis of the analysis. Significantly more Staphylococcus
      aureus isolates (P = 0.03), Staphylococcus epidermidis isolates (P = 0.03),
      members of the family Enterobacteriaceae (P = 0.03), and Pseudomonas aeruginosa
      isolates (P = 0.04) were recovered from the resin bottle, and there was no
      category of organism that was recovered significantly more frequently from the
      Isolator system. With patients receiving antibiotics at the time of blood
      culture, S. aureus, S. epidermidis, and gram-negative bacilli were recovered
      significantly more frequently from the resin bottle. No significant differences
      between systems were found with cultures from patients not receiving antibiotics
      at the time of blood culture. Only 12 clinically significant organisms were
      recovered from the bottle on terminal subcultures, and only 1 of these had not
      been previously isolated from another blood culture set (10 of the 12) or from
      the companion Isolator (1 of 12). The Aerobic/F resin bottle continuously
      monitored in the BACTEC 9240 instrument proved to be superior to the Isolator in
      overall yield of organisms causing bloodstream infection in adults and required
      less technician time for specimen processing and examination than the Isolator
      system.

PMID- 8567878
TI  - Monitoring of leukocyte cytomegalovirus DNA in bone marrow transplant recipients
      by nested PCR.
AB  - A nested PCR assay for the detection of human cytomegalovirus (CMV) DNA was
      evaluated by weekly monitoring of blood samples taken from 101 bone marrow
      transplant (BMT) recipients. When peripheral blood leukocytes were used as the
      source of CMV DNA, even a modified assay with stringent temperature-cycling
      conditions was as sensitive as the standard assay. The sensitivity, specificity,
      and positive predictive value of two consecutively positive leukocytic PCR
      results with this modified assay in predicting CMV disease of 101 patients
      submitting 1,441 peripheral blood leukocyte samples were found to be 92.1, 63.5,
      and 60.3%, respectively. The positive predictive value of patients'
      seropositivity for CMV was 40%, while that of viremia was 72%. However, viremia
      followed CMV disease by a median of 1.5 days, while the first leukocytic positive
      PCR assay preceded disease by a median of 14 days. By use of the criteria of two
      consecutively positive PCR results instead of recipient CMV seropositivity for
      starting preemptive ganciclovir treatment, 38 of the 43 recipients with isolated
      single positive or negative assays (groups I and II) would be spared unnecessary
      ganciclovir treatment. Moreover, two other findings support the use of antiviral
      prophylaxis before engraftment in high-risk cases and subsequent preemptive
      treatment of patients with two consecutively positive PCR assays. First, for 7.9%
      of 76 patients with positive assays (groups II and III), the first positive PCR
      assay occurred before engraftment, which implied the presence of viral DNA in the
      blood (DNAemia) soon after transplantation. Second, isolated single positive
      assays which were clustered around the second to sixth weeks after
      transplantation were found for 18 patients (group II) and could represent
      abortive episodes of CMV infection.

PMID- 8567879
TI  - Recombinant mono- and polyantigens to detect cytomegalovirus-specific
      immunoglobulin M in human sera by enzyme immunoassay.
AB  - Serological detection of human cytomegalovirus (HCMV)-specific antibody varies
      greatly because of antigen composition and the lack of antigen standardization.
      Antigenic materials composed of single well-characterized viral proteins or
      portions of them, produced via molecular biology, have proven to be promising
      tools in improving serodiagnosis. We constructed a recombinant protein containing
      two regions of ppUL32 (p150) and half of ppUL44 (p52) and compared the
      immunoglobulin M (IgM) reactivity of this triple-antigen fusion protein with that
      of a double-antigen fusion protein containing the two ppUL32 fragments and that
      of a monoantigen fusion protein containing half of ppUL44. We also constructed
      and tested two other monoantigen fusion proteins containing a large fraction of
      ppUL80a and a fraction of ppUL83. More than 700 serum samples from different
      groups of immunocompetent and immunosuppressed subjects were tested for the
      presence of HCMV IgM by recombinant enzyme immunoassay (rec-EIA) and by a
      commercially available EIA. Western blotting (immunoblotting) and (in the case of
      immunosuppressed individuals) antigenemia tests by immunofluorescence and PCR of
      polymorphonuclear leukocytes were also carried out. The results obtained
      demonstrate that (i) the triple-antigen fusion protein can replace the individual
      proteins; (ii) the triple-antigen fusion protein cannot be used alone to replace
      the virus or infected cells in the serological detection of anti-CMV IgM; (iii)
      the addition of the fusion proteins containing portions of ppUL83 and ppUL80a is
      essential for the formation of an antigenic mixture that can replace the virus
      for the search of HCMV-specific IgM; (iv) rec-EIA is very specific and is more
      sensitive than the commercially available EIA, and the results obtained are
      consistent with those obtained by Western blotting; and (v) rec-EIA can reliably
      be used to detect HCMV-specific IgM in different groups of patients with active
      HCMV infection.

PMID- 8567880
TI  - Increased expression of Candida albicans secretory proteinase, a putative
      virulence factor, in isolates from human immunodeficiency virus-positive
      patients.
AB  - The increased prevalence and the severity of oropharyngeal candidiasis in human
      immunodeficiency virus (HIV)-positive patients are attributed exclusively to the
      virus-induced immune deficiency of the host. The present study was aimed at
      answering the question of whether Candida albicans secretory proteinase, a
      putative virulence factor of the opportunistic C. albicans yeast, has any
      potential influence on the clinical manifestation of oropharyngeal candidiasis in
      HIV-positive patients. We measured the secretory proteinase activities of
      clinical C. albicans isolates from the oropharynges of either HIV-positive
      individuals (n = 100) or a control group (n = 122). The mean secretory proteinase
      activity of C. albicans isolates from the HIV-positive group (4,255 +/- 2,372
      U/liter) was significantly higher compared with that of isolates from the control
      group (2,324 +/- 1,487 U/liter) (P < 0.05). The higher level of secretory
      proteinase activity in the culture supernatants of individual C. albicans
      isolates correlated with the increased level of proteinase expression on the cell
      surface, as revealed by cytofluorometry, and with higher levels of secretion of
      the immunodetectable protein, as shown by Western blotting (immunoblotting).
      Proteinase activity within the population of C. albicans isolates from HIV
      positive individuals was independent of the patient's clinical disease stage and
      the CD4+/CD8+ cell numbers. Furthermore, no correlation of the proteinase
      activities with the C. albicans serotype was found, although C. albicans serotype
      B was significantly more frequent in the HIV-positive group (40%) compared with
      that in the control group (12%). However, a positive correlation of proteinase
      activity to antifungal susceptibility was evident. The C. albicans isolates from
      the HIV-positive group that were characterized by higher levels of proteinase
      activity were also less susceptible to the widely used azole antifungal
      ketoconazole and fluconazole. Collectively, the present data are consistent with
      a concept of early preferential selection of a subpopulation of C. albicans in
      HIV-infected patients.

PMID- 8567881
TI  - Factors which influence levels of selected organisms in saliva of older
      individuals.
AB  - The most commonly measured bacterial parameters in saliva are the levels of the
      mutans group streptococci and lactobacilli, which have diagnostic implications
      for the incidence of dental decay. Diagnostic guidelines which are applicable to
      children and young adults in whom most, if not all, teeth are present and in whom
      the rate of stimulated saliva is almost always greater than 0.5 ml/min have been
      developed. Dental decay is a potential health problem of considerable magnitude
      among elderly individuals. In elderly individuals, missing teeth, the presence of
      dentures, and a reduced salivary flow could confound the interpretation of
      salivary levels of cariogenic bacteria. In the present study, in which saliva was
      collected from more than 560 elderly individuals (average age, 70 +/- 8 years),
      there was a significant positive relationship between the salivary levels of
      Streptococcus mutans and increased numbers of teeth. There was a positive
      association between the salivary levels of S. mutans and decay when the data were
      stratified for the presence of a complaint of xerostomia and the presence of
      dentures. However, a similar analysis indicated that lactobacilli and yeasts were
      more likely to be associated with decay. The various variables which could
      influence the bacterial counts per milliliter of saliva, e.g., independent or
      dependent living status, complaint of xerostomia, stimulated salivary flow,
      salivary pH, the presence of dentures, number of teeth, and decay, were analyzed
      simultaneously by using a multivariable linear model. In that analysis the number
      of decayed teeth was significantly associated with the presence of lactobacilli
      (P = 0.0001) and yeasts (P = 0.025) but not with the presence of S. mutans. Our
      findings indicate that salivary levels of lactobacilli and yeasts, as well as the
      salivary levels of S. mutans, should be monitored when seeking microbial
      indicators that might predict the incidence of caries in elderly individuals.

PMID- 8567882
TI  - Rapid diagnosis of Entamoeba infection by using Entamoeba and Entamoeba
      histolytica stool antigen detection kits.
AB  - Humans are infected by two morphologically identical species of Entamoeba:
      Entamoeba histolytica causes amebic colitis and liver abscess, and Entamoeba
      dispar is noninvasive. Several weeks of culture and isoenzyme (zymodeme) analysis
      are required to differentiate E. histolytica from E. dispar. Here we report a
      field trial of commercial antigen detection kits designed to rapidly detect and
      differentiate E. histolytica from E. dispar in stool specimens. Stool specimens
      from 202 patients with diarrhea were examined for E. histolytica and E. dispar by
      microscopy, culture, and antigen detection. Compared with culture, microscopic
      identification of the E. histolytica-E. dispar complex was 60% sensitive and 79%
      specific, while the screening antigen detection test for the E. histolytica-E.
      dispar complex was 80% sensitive and 99% specific. Differentiation of E. dispar
      from E. histolytica by the E. histolytica-specific test was 95% sensitive and 93%
      specific compared with zymodeme analysis. We conclude that the antigen detection
      test for the E. histolytica-E. dispar complex is more sensitive and specific than
      microscopy and that the E. histolytica-specific antigen detection test is as
      reliable and much more rapid than zymodeme analysis for the differentiation of E.
      histolytica from E. dispar.

PMID- 8567883
TI  - Comparative study of five methods for intratypic differentiation of polioviruses.
AB  - A coded panel of 90 poliovirus isolates, 30 of each of the three known serotypes,
      was used to evaluate five methods for the intratypic differentiation of
      polioviruses: (i) an enzyme-linked immunosorbent assay with polyclonal cross
      absorbed antisera (PAb-E), (ii) a neutralization assay with type-specific
      monoclonal antibodies (MAb-N), (iii) a restriction fragment length polymorphism
      (RFLP) assay, (iv) a Sabin vaccine strain-specific PCR assay, and (v) a Sabin
      vaccine strain-specific cRNA probe hybridization (ProHyb) assay. Sequence
      analysis was used for the definitive characterization of the strains. The panel
      was distributed to five laboratories; each laboratory analyzed the strains by at
      least two methods. Each method was used by three or four laboratories. The total
      performance scores (percentage correct results per number of tests) of the five
      methods were 96.7% for PAb-E, 93.9% for MAb-N, 91.9% for RFLP assay, 93.3% for
      Sabin vaccine strain-specific PCR, and 97.4% for Sabin vaccine strain-specific
      ProHyb. Consistent results were obtained by each laboratory for 88 of 90 isolates
      (97.8%) examined by PAb-E, 81 of 90 isolates (90.0%) examined by MAb-N, 78 of 90
      isolates (86.7%) examined by RFLP assay, 81 of 90 isolates (90.0%) examined by
      PCR, and 89 of 90 isolates (98.9%) examined by ProHyb assay. Six strains were
      classified differently by different methods. It is recommended that at least two
      methods be used for the intratypic differentiation of poliovirus isolates, and
      each method should be based on a different principle (i.e., antigenic properties
      and nucleotide sequence composition). If two assays yield discrepant results,
      further characterization, preferably by partial sequence determination, will be
      required for correct identification.

PMID- 8567884
TI  - Phenotypic and genotypic analysis of variability in Aspergillus fumigatus.
AB  - Sixty-one isolates and collection strains of Aspergillus fumigatus were compared
      for their phenotypic (morphological features and isoenzyme profiles) and
      genotypic (restriction enzyme-generated mitochondrial DNA and ribosomal DNA
      profiles and random amplified polymorphic DNA patterns) features. The examined
      strains exhibited highly variable colony morphologies and growth rates at
      different temperatures, but their micromorphologies and conidial diameters were
      characteristic of the species. Of the isoenzymes studied, the beta-arylesterase
      and phosphatase patterns were the most divergent, and the 61 strains could be
      classified into seven groups. The glucose 6-phosphate dehydrogenase and catalase
      isoenzyme patterns displayed only a limited variability, while the profiles of
      superoxide dismutase, lactate dehydrogenase, and glutamate dehydrogenase were
      highly conserved. The HaeIII-generated mitochondrial DNA patterns and SmaI
      digested repetitive DNA and ribosomal DNA hybridization patterns of almost all
      strains were also invariable. The level of variation was much higher when random
      amplified polymorphic DNA analysis was applied. Although the patterns of the
      strains were very similar with most of the primers, the application of some
      primers made it possible to cluster the A. fumigatus isolates into several
      groups. The results indicate that the random amplified polymorphic DNA technique
      could be used more efficiently than isoenzyme analysis for typing A. fumigatus
      isolates. A good correlation was found between the dendrograms obtained from the
      isoenzyme and random amplified polymorphic DNA data, but the isoenzyme and
      amplified DNA patterns did not correlate with the pathogenicity, pigment
      production, or geographical origin of the strains. One "A. fumigatus" strain
      (strain FRR 1266) exhibited unique isoenzyme, mitochondrial DNA, ribosomal DNA,
      and random amplified polymorphic DNA patterns; it is proposed that this strain
      represents a new species of the section Fumigati.

PMID- 8567885
TI  - Characterization of Streptococcus agalactiae strains by multilocus enzyme
      genotype and serotype: identification of multiple virulent clone families that
      cause invasive neonatal disease.
AB  - The chromosomal genotypes of 277 isolates of 16 serotypes of Streptococcus
      agalactiae were characterized by analysis of electrophoretically demonstrable
      allele profiles at 12 metabolic enzyme loci. The collection comprised the type
      strain and 276 strains recovered from French symptomatic and asymptomatic
      subjects. Sixty-one distinctive electrophoretic types (ETs), representing
      multilocus clonal genotypes, were identified. Cluster analysis of the ETs
      revealed two primary phylogenetic divisions separated by a genetic distance of
      0.62, Division I contained 67 isolates which could be assigned to 13 ETs. Twenty
      seven of these isolates were from samples of cerebrospinal fluid (CSF) from
      neonatal meningitis patients. Two ETs, separated by a genetic distance of 0.217,
      contained 26 of these 27 isolates. Division II contained 210 isolates, of which
      27 were isolated from CSF. This division was more polymorphic and included 48
      ETs. Spanning a genetic distance of 0.3, three clusters and one ET were
      identified within this group. Twenty-four of 27 strains isolated from CSF
      belonged to one cluster, and 19 of them belonged to two adjacent ETs with a
      genetic distance of 0.083. Fifty-five of the 68 serotype Ia strains and 24 of the
      26 serotype Ib strains were each confined to one of the evolutionary lineages,
      and 85 of the 86 strains which carried protein antigen c belonged to phylogenetic
      division II. Most of the type III organisms were assigned to two clone families.
      The characteristics of this French population argue for the existence of
      particular groups of strains responsible for neonatal meningitis and demonstrate
      that serotyping can supply information about the genetic distribution of strains.

PMID- 8567886
TI  - Evaluation of Amplicor PCR for direct detection of Mycobacterium tuberculosis
      from sputum specimens.
AB  - We evaluated the Amplicor PCR assay (Roche Molecular Systems, Branchburg, N.J.)
      for direct detection of Mycobacterium tuberculosis in sputum. A total of 532
      specimens from 270 patients were decontaminated and stored at 4 or -75 degrees C
      until assayed by PCR. This assay used three-step sample preparation, biotinylated
      primer pairs, AmpErase, and a microtiter format for amplicon capture and
      detection. Amplicor PCR results were compared with clinical history, culture from
      a Lowenstein-Jensen slant, and results from the BACTEC TB-460 system. Eighty
      seven cultures from 15 patients grew M. tuberculosis; of these, 83 (95%) were
      positive with the Amplicor PCR test. The false negatives were most likely due to
      sample variation and inhibitors. Of the 445 specimens from which M. tuberculosis
      was not isolated, 428 (96%) were negative with the Amplicor PCR test. Of the 17
      M. tuberculosis culture-negative, Amplicor-positive specimens, 15 were
      reclassified as true positives because previous cultures grew M. tuberculosis. Of
      the 445 specimens which did not grow M. tuberculosis, Mycobacterium spp. other
      than M. tuberculosis were isolated from 150 specimens. Three of these 150
      specimens were Amplicor positive; two were from a patient with a history of
      tuberculosis, and one specimen gave a false-positive result. We do not feel that
      this represents cross-reactivity, because repeated Amplicor testing of the
      isolate gave negative results. The microtiter plate has 96 wells. Allowing for
      six controls, 90 decontaminated specimens can be tested by one technologist in
      7.5 h. This PCR assay took 7.5 h to complete and is a sensitive and specific,
      rapid method for the direct detection of M. tuberculosis from sputum.

PMID- 8567887
TI  - Evaluation of nucleic acid-based test (PACE 2C) for simultaneous detection of
      Chlamydia trachomatis and Neisseria gonorrhoeae in endocervical specimens.
AB  - A nucleic acid-based test (Gen-Probe PACE 2C System) was evaluated for the
      ability to detect Chlamydia trachomatis and Neisseria gonorrhoeae from
      endocervical specimens in a single assay. Three swab samples, randomized for
      collection order, were obtained from each patient and tested by N. gonorrhoeae
      and C. trachomatis culture and by the PACE 2C probe assay. Fifty of 395 specimens
      were culture positive for N. gonorrhoeae (17 specimens), C. trachomatis (26
      specimens), or both (7 specimens), of which PACE 2C testing detected 48
      specimens. The PACE 2C assay was positive for 56 specimens, including 8 specimens
      not positive by culture. Of the total of 10 discrepancies between culture and
      PACE 2C results, resolution testing yielded four false-negative culture, four
      false-positive PACE 2C, and two false-negative PACE 2C results. The sensitivity,
      specificity, and positive and negative predictive values for PACE 2C after
      reevaluation were 96.3, 98.8, 92.9 and 99.4%, respectively. The overall
      sensitivities for C. trachomatis and N. gonorrhoeae culture were 89.2 and 88.9%,
      respectively. The prevalence rate for C. trachomatis was 9.4%, and that for N.
      gonorrhoeae was 6.8%. The Gen-Probe PACE 2C System is a reliable alternative for
      screening endocervical specimens for both C. trachomatis and N. gonorrhoeae in a
      single assay.

PMID- 8567888
TI  - Effect of three concentration techniques on viability of Cryptosporidium parvum
      oocysts recovered from bovine feces.
AB  - Bovine fecal samples (1 g) negative for Cryptosporidium sp. oocysts were seeded
      with 7 x 10(4) Cryptosporidium parvum oocysts and purified by either water-ether
      concentration, sucrose density flotation, or zinc sulfate flotation to evaluate
      oocyst recovery. The effect of these purification techniques on the viability of
      recovered oocysts was also evaluated. Significantly higher numbers of seeded
      oocysts were recovered by water-ether concentration (recovery rate, 46 to 75%)
      than by sucrose density (24 to 65%) or zinc sulfate (22 to 41%) flotation
      methods. In addition, water-ether concentration did not exert a significant
      effect on the viability of the population of oocysts recovered, whereas sucrose
      density flotation and zinc sulfate flotation selectively concentrated viable
      oocysts. The water-ether concentration procedure is recommended for use in
      epidemiological studies in which both oocyst enumeration and viability assessment
      are required.

PMID- 8567889
TI  - Establishment of enzyme-linked immunosorbent assay using purified recombinant 83
      kilodalton antigen of Borrelia burgdorferi sensu stricto and Borrelia afzelii for
      serodiagnosis of Lyme disease.
AB  - The 83-kDa antigen of Borrelia burgdorferi was expressed as a recombinant protein
      in Escherichia coli and purified for use in an enzyme-linked immunosorbent assay
      (p83-ELISA). Antibodies to the 83-kDa antigen of both the immunoglobulin G (IgG)
      and IgM isotypes could be detected in all stages of Lyme disease. Sensitivity
      varied, depending on the clinical stage of illness. In early stages, as defined
      for 118 patients with erythema migrans, it was found to be 20% (24 of 118
      patients: 7 with IgM, 16 with IgG, and 1 with IgM and IgG). Of the patients with
      late-stage Lyme arthritis and acrodermatitis chronica atrophicans, 94% (16 of
      17:2 with IgM and IgG and 14 with IgG) and 86% (36 of 42:2 with IgG and IgM and
      34 with IgG) revealed positive results in the p83-ELISA, respectively. p83
      displays sequence heterogeneity according to the genomospecies, but when the
      reactions of serum specimens from acrodermatitis chronica atrophicans patients
      and arthritis patients with p83 derived from representative strains of B.
      burgdorferi sensu stricto and Borrelia afzelii in ELISAs were compared, no
      differences in specificity and sensitivity were seen. When 82 serum specimens
      from healthy controls were tested, none had IgG and only 3 (4%) had IgM
      antibodies, indicating a high specificity. Positive reactions with antibodies
      against Treponema pallidum (1 of 37 patients; IgG) and Epstein-Barr virus (1 of
      44 patients; IgM) and with autoantibodies of various specificities (1 of 53
      patients; IgG) were seen with < 3% of the serum samples te11111111111111111111
      high speficicity for B. burgdorferi.2+ 13% for IgM antibodies, the IgM p83-ELISA
      provided little diagnostic information for Lyme disease, whereas the IgG p83
      ELISA appears to be a suita ;e test for serodiagnosis of advanced-stage Lyme
      disease.

PMID- 8567890
TI  - Molecular identification of bacteria by fluorescence-based PCR-single-strand
      conformation polymorphism analysis of the 16S rRNA gene.
AB  - PCR-single-strand conformation polymorphism (PCR-SSCP) analysis is a rapid and
      convenient technique for the detection of mutations and allelic variants. We have
      adapted this technique for the identification of bacteria by PCR with fluorescein
      labeled primers chosen from the conserved regions of the 16S rRNA gene flanking a
      variable region. The PCR product was denatured, separated on a nondenaturing gel,
      and detected by an automated DNA sequencer. The mobility of the single-stranded
      DNA is sequence dependent and allows the identification of a broad panel of
      bacteria. A single nucleotide difference in the amplified region was sufficient
      to obtain different PCR-SSCP patterns. The simultaneous amplification of multiple
      polymorphic regions by multiplex PCR with subsequent multiplex SSCP increased the
      discriminatory power of PCR-SSCP. A broad range of gram-negative and gram
      positive bacteria were tested by PCR-SSCP, including, e.g., Escherichia coli,
      Enterobacter spp., Klebsiella spp., Haemophilus spp., Neisseria spp.,
      Staphylococcus spp, Streptococcus spp., Enterococcus spp., and Bacillus spp. In
      total, a panel of 178 strains of bacteria representing 51 species in 21 genera
      was examined. Although a limited number of strains from each species were tested,
      the strains tested gave species-specific patterns, with only one exception:
      Shigella species were indistinguishable from E. coli. PCR is a sensitive
      technique; as few as 10 CFU of E. coli was sufficient to produce PCR-SSCP
      patterns suitable for identification. The whole fluorescence PCR-SSCP procedure
      takes approximately 8 h for the detection and identification of low numbers of
      bacteria.2+ fluorescence PCR-SSCP seems to be a promising method for the
      differentiation of a broad range of pathogens found in usually sterile clinical
      sites, such as blood and cerebrospinal fluid.

PMID- 8567891
TI  - Human cytomegalovirus (CMV) DNA in plasma reflects quantity of CMV DNA present in
      leukocytes.
AB  - A quantitative DNA amplification assay for human cytomegalovirus (CMV) DNA has
      been used to evaluate the relationship between quantities of CMV DNA in plasma
      and those in infected leukocytes (WBC) from human immunodeficiency virus-infected
      patients. The target sequence for DNA amplification was a region of the immediate
      early 1 gene of CMV. The quantitation assay uses an internal control that is
      coamplified with each patient sample DNA and contains a sequence for detection by
      colorimetric hybridization with the same bases, but in different order than in
      the CMV immediate-early 1 region used for hybridization of amplified patient
      sample DNA. Results showed that patients with CMV disease had more CMV DNA in
      both WBC and plasma than those without disease. However, in this study, copy
      numbers of CMV DNA in WBC were higher than those in plasma. The gB and gH
      variants were the same in plasma and WBC.

PMID- 8567892
TI  - Torulopsis glabrata: azole susceptibilities by microdilution colorimetric and
      macrodilution broth assays.
AB  - Fluconazole and itraconazole MICs were determined by both the standard
      macrodilution method of the National Committee for Clinical Laboratory Standards
      and a colorimetric broth microdilution method for 140 isolates of Torulopsis
      (Candida) glabrata obtained over a 15-year period. Using the method of the
      National Committee for Clinical Laboratory Standards the MICs at which 90% of
      isolates are inhibited (MIC50) for all isolates were 32 and 1.6 micrograms/ml for
      fluconazole and itraconazole, respectively. For fluconazole, the MIC90 rose from
      16 to > 64 micrograms/ml when the MIC90s for isolates collected from July 1980 to
      June 1991 were compared with those for isolates collected from July 1991 to March
      1995. For itraconazole, the MIC90s for isolates from the same time periods were
      0.8 and 3.2 micrograms/ml, respectively. Although for isolates from some non
      human immunodeficiency virus-infected patients the MICs rose, most of the high
      MICs were found for isolates from human immunodeficiency virus-infected patients
      who had been extensively treated with azole drugs for thrush. The colorimetric
      method yielded endpoints that were more definitive; concordances within 2
      dilutions for the two methods were 87% for fluconazole and 86% for itraconazole.

PMID- 8567893
TI  - Sensitivity of bacteriologic culture for detection of Escherichia coli O157:H7 in
      bovine feces.
AB  - The sensitivities of several plating and broth enrichment methods for the
      detection of Escherichia coli O157:H7 in (i) bovine fecal samples directly
      inoculated with E. coli O157:H7, (ii) fecal samples from cattle in herds
      previously positive for E. coli O157:H7, and (iii) fecal samples from calves
      shedding E. coli O157:H7 after experimental oral inoculation were compared. Three
      enrichment protocols and three plating protocols were evaluated with directly
      inoculated fecal samples. All broth enrichment methods were superior to direct
      plating when they were combined with subsequent plating on sorbitol-MacConkey
      with cefixime and tellurite (SMACct). SMACct was the most sensitive plating
      medium, and the three alternative broth enrichment methods gave similar
      improvements in sensitivity. Of 351 fecal samples from known positive herds, 24
      samples (6.8%) were positive by one or more methods. By the most sensitive
      plating method, cultures of 10-g samples were slightly more sensitive (19 of 351
      [5.4%]) than cotton-tipped swab fecal samples (14 of 351 [4.0%]); however, this
      difference was not significant. For samples from calves orally inoculated with E.
      coli O157:H7, separation by immunomagnetic beads was slightly more sensitive
      (79%) than broth enrichment followed by plating at two dilutions (10(-3) and 10(
      4)) (71%); however, this difference was not significant. The combination of
      overnight enrichment of swab fecal samples (0.1 g) and plating on SMACct at two
      dilutions (10(-3) and 10(-4)) appears to be a sensitive method for detection in
      large-scale studies involving hundreds of samples per week.

PMID- 8567894
TI  - Use of PCR and direct immunofluorescence microscopy for confirmation of results
      obtained by Syva MicroTrak Chlamydia enzyme immunoassay.
AB  - A procedure for use of the Amplicor Chlamydia PCR with the Syva MicroTrak enzyme
      immunoassay (EIA) medium was developed, and the performance of the Syva MicroTrak
      EIA was evaluated by use of PCR and the Syva MicroTrak direct immunofluorescence
      assay (DFA) as confirmatory methods. PCR detected Chlamydia organisms at a 10
      fold greater dilution than did DFA. Of 366 specimens, 119 specimens were positive
      by both PCR and DFA, 6 specimens were positive only by PCR, and 241 specimens
      were negative by both PCR and DFA. Subsequently, DFA and the developed PCR
      procedure were used prospectively for confirmation of EIA results in a defined
      negative gray zone between the cutoff value and 30% of the cutoff value (70%
      below the cutoff value). All specimens with results above the EIA cutoff value
      were also subjected to confirmation with DFA and PCR. EIA was performed on 7,748
      endocervical swab specimens, of which 494 (6.4%) were subjected to confirmation,
      and on 968 male urethral swab specimens, of which 185 (19.1%) were subjected to
      confirmation. A "gold standard" was based on the findings by DFA and PCR, and
      divergent results were resolved by a major outer membrane protein-based PCR.
      Forty-five of 160 female specimens (28.1%) and 11 of 93 male specimens (11.8%)
      within the defined negative gray zone were found to be positive. Of 334 female
      specimens having absorbance unit (AU) values above the EIA cutoff value, 258
      could be confirmed, thereby giving a positive predictive value of 77% (258/334).
      Accordingly, the positive predictive value with male specimens was 95% (87/92).
      The prevalence of Chlamydia trachomatis-positive specimens was 3.9% (303/7,748)
      in females and 10.1% (98/968) in males. All male specimens having AU values above
      1.0 in the EIA were confirmed positive. In contrast to this, 16 females with AU
      values above 1.0 in the EIA could not be confirmed positive with either DFA or
      PCR. The mean age of these females was higher than that of patients testing
      negative for C. trachomatis (P < 0.005). This might suggest an age-dependent
      change in vaginal colonization with an organism(s) crossreacting in the EIA.
      Thus, the PCR procedure developed can be used for confirmation of EIA results,
      testing specimens with AU values in the defined negative gray zone improves the
      sensitivity of EIA, and all specimens testing positive in EIA should be subjected
      to confirmation.

PMID- 8567896
TI  - Intermethod variation in detection of human papillomavirus DNA in cervical
      smears.
AB  - In order to investigate the reliability of detection of human papillomavirus
      (HPV) DNA in cervical smears, we have compared the performance of two HPV PCR
      systems, the CPI/IIG and MY09/11 primer-mediated PCRs and the Hybrid Capture
      System HPV DNA detection test (hybrid capture assay), in detecting HPV DNA in
      cervical smears. We also included in our study the MY09/11B PCR plus SHARP
      (solution hybridization assay for PCR products) Signal System. This SHARP Signal
      System was recently developed to detect MY09/11B-generated biotinylated PCR
      products. The detection rate of the hybrid capture assay was lower than those of
      the CPI/IIG and MY09/11 PCRs and the MY09/11B PCR plus SHARP Signal System. The
      detection rates of the CPI/IIG PCR and the MY09/11B PCR plus SHARP Signal System
      were similar and higher than that of the conventional MY09/11 PCR system. The
      agreement beyond chance of the PCR methods was nearly perfect (kappa value
      between 0.82 and 0.84). The agreement beyond chance of the hybrid capture assay
      and the PCR methods was fair to good (kappa value between 0.64 and 0.70). The
      systems detected HPV DNA in different but overlapping sets of smears. Our results
      indicate that each of the detection methods alone underestimates the prevalence
      of HPV.

PMID- 8567897
TI  - Ribotyping for use in studying molecular epidemiology of Serratia marcescens:
      comparison with biotyping.
AB  - Ribotyping carried out with a nonradioactive probe (acetylaminofluorene ribosomal
      RNA kit I from Eurogentec, Seraing, Belgium) was performed for the
      characterization of 139 hospital strains of Serratia marcescens. These strains,
      which belonged to 11 biotypes and 1 nontypeable group, were isolated in seven
      hospitals in Belgium between 1986 and 1992. EcoRI and HindIII were used to obtain
      cleavage patterns. Analysis of the results produced 27 different patterns with
      EcoRI and 23 patterns with HindIII. Typeability reached 100%. Combination of the
      patterns obtained with each enzyme produced 38 distinct ribotypes. Percent
      similarity values, calculated by using the Dice coefficient and unweighted-pair
      group average linkage clustering, showed four main clusters and nine subclusters
      of ribopatterns at a similarity rate of approximately 80% or less. These groups
      did not coincide with those delimited by biotyping, although a rather good
      correlation was observed. The simultaneous use of the two methods has potential
      value in epidemiological studies.

PMID- 8567895
TI  - Characterization of Newcastle disease virus isolates by reverse transcription PCR
      coupled to direct nucleotide sequencing and development of sequence database for
      pathotype prediction and molecular epidemiological analysis.
AB  - Degenerate oligonucleotide primers were synthesized to amplify nucleotide
      sequences from portions of the fusion protein and matrix protein genes of
      Newcastle disease virus (NDV) genomic RNA that could be used diagnostically.
      These primers were used in a single-tube reverse transcription PCR of NDV genomic
      RNA coupled to direct nucleotide sequencing of the amplified product to
      characterize more than 30 NDV isolates. In agreement with previous reports,
      differences in the fusion protein cleavage sequence that correlated genotypically
      with virulence among various NDV pathotypes were detected. By using sequences
      generated from the matrix protein gene coding for the nuclear localization
      signal, lentogenic viruses were again grouped phylogenetically separate from
      other pathotypes. These techniques were applied to compare neurotropic velogenic
      viruses isolated from an outbreak of Newcastle disease in cormorants and turkeys.
      Cormorant NDV isolates and an NDV isolate from an infected turkey flock in North
      Dakota had the fusion protein cleavage sequence 109SRGRRQKRFVG119. The R-for-G
      substitution at position 110 may be unique for the cormorant-type isolates.
      Although the amino acid sequences from the fusion protein cleavage site were
      identical, nucleotide sequence data correlate the outbreak in turkeys to a
      cormorant virus isolate from Minnesota and not to a cormorant virus isolate from
      Michigan. On the basis of sequence information, the cormorant isolates are
      virulent viruses related to isolates of psittacine origin, possibly genotypically
      distinct from other velogenic NDV isolates. These techniques can be used reliably
      for Newcastle disease epidemiology and for prediction of pathotypes of NDV
      isolates without traditional live-bird inoculations.

PMID- 8567898
TI  - Inhibition of PCR by aqueous and vitreous fluids.
AB  - The detection of viral nucleic acids in intraocular fluids and tissues by PCR has
      become increasingly important in clinical ophthalmology. While much attention has
      been directed toward minimizing false-positive reactions resulting from specimen
      contamination or amplicor carryover, relatively little attention has been given
      to the causes of false-negative PCRs. This report describes a PCR inhibitor in
      normal aqueous and vitreous fluids that can produce false-negative PCR results.
      As little as 0.5 microliter of vitreous fluid and 20 microliters of aqueous fluid
      can completely inhibit DNA amplification in a 100-microliters PCR mixture. This
      inhibition was not primer specific, nor was it due to chelation of Mg2+ ions or
      DNase activity in the ocular fluid. The inhibitor was completely resistant to
      boiling for 15 min. However, the inhibitory effects were completely removed by a
      single chloroform-isoamyl alcohol (24:1) extraction. The extent of PCR inhibition
      depended upon the type of thermostable DNA polymerase used in the reaction. Taq
      DNA polymerase was very sensitive to the inhibitor, while thermostable DNA
      polymerases from Thermus thermophilus HB-8 (Tth) and Thermus flavus (Tfl) were
      completely resistant. Thus, the inhibitory effects of intraocular fluids on PCRs
      can be removed by diluting the specimen, by chloroform extraction, or by using
      Tth or Tfl DNA polymerases.

PMID- 8567899
TI  - Monoclonal antibodies to detect capsular diversity among Bacteroides fragilis
      isolates.
AB  - The capsular polysaccharide complex (CPC) of Bacteroides fragilis is composed of
      two distinct polysaccharides, designated PS A and PS B, and is a major virulence
      factor of this microorganism. In order to investigate the antigenic diversity of
      the CPCs of B. fragilis strains, we generated and characterized 10 monoclonal
      antibodies (MAbs) directed to the CPCs of three reference strains. The
      specificities of the MAbs were determined by enzyme-linked immunosorbent assay
      and dot-immunobinding assay. At least one MAb was specific for each PS A and PS B
      of the three strains. The MAbs were used to detect capsular antigens on the
      surface of 231 B. fragilis isolates from different geographical areas by a whole
      cell dot-immunobinding assay. Over half of the strains, regardless of the country
      of origin, reacted with at least one MAb. Clinical extraintestinal infection
      isolates were significantly more reactive than fecal isolates, suggesting an
      association between capsular composition and the propensity to cause clinical
      infections. The patterns of reactivity of the isolates with the 10 MAbs were very
      different and sometimes extremely complex and indicated a sharing of epitopes
      among different capsular polysaccharides. The reactive strains could be grouped
      according to 32 different patterns; some patterns were relatively common, while
      others were rarer and were shown by only one or two strains. These results show
      that B. fragilis capsular polysaccharides are antigenically extremely diverse.
      This complexity and the large number of nonreactive strains indicate that a
      typing system based on B. fragilis capsular antigens will be difficult to
      establish.

PMID- 8567900
TI  - An Indian strain of hepatitis E virus (HEV): cloning, sequence, and expression of
      structural region and antibody responses in sera from individuals from an area of
      high-level HEV endemicity.
AB  - Hepatitis E virus (HEV) is responsible for a majority of sporadic and epidemic
      viral hepatitides in India and other developing countries. Even though the
      genomes of four geographically distinct strains of HEV have been cloned and
      sequenced, the Indian strain of HEV remains largely uncharacterized. We have
      cloned and sequenced about 2.2 kb of the HEV genome constituting the structural
      region from an Indian strain of HEV. The nucleotide and amino acid sequences show
      a high degree of conservation with sequences from other HEV strains. Open reading
      frames (ORF) 2 and 3 were expressed in Escherichia coli as N-terminal
      hexahistidine epitope fusions. The purified proteins were then used in an
      immunoblot assay to evaluate the antibody status in sera from individuals from an
      area of high-level HEV endemicity. The anti-ORF2 antibodies were found to be
      nonspecific and could not be correlated to clinical disease. The immunoglobulin M
      anti-ORF3 was found to be specific for the presence of acute disease. The
      implications of these findings in HEV diagnosis and vaccine development are
      discussed.

PMID- 8567901
TI  - Comparative evaluation of macrodilution and alamar colorimetric microdilution
      broth methods for antifungal susceptibility testing of yeast isolates.
AB  - A comparative evaluation of the macrodilution method and the Alamar colorimetric
      method for the susceptibility testing of amphotericin B, fluconazole, and
      flucytosine was conducted with 134 pathogenic yeasts. The clinical isolates
      included 28 Candida albicans, 17 Candida tropicalis, 15 Candida parapsilosis, 12
      Candida krusei, 10 Candida lusitaniae, 9 Candida guilliermondii, 18 Torulopsis
      glabrata, and 25 Cryptococcus neoformans isolates. The macrodilution method was
      performed and interpreted according to the recommendations of the National
      Committee for Clinical Laboratory Standards (document M27-P), and the Alamar
      colorimetric method was performed according to the manufacturer's instructions.
      For the Alamar colorimetric method, MICs were determined at 24 and 48 h of
      incubation for Candida species and T. glabrata and at 48 and 72 h of incubation
      for C. neoformans. The overall agreement within +/- 1 dilution for Candida
      species and T. glabrata against the three antifungal agents was generally good,
      with the values for amphotericin B, fluconazole, and flucytosine being 85.3,
      77.9, and 86.2%, respectively, at the 24-h readings and 69.3, 65.2, and 97.2%,
      respectively, at the 48-h readings. Most disagreement was noted with fluconazole
      against C. tropicalis and T. glabrata. Our studies indicate that determination of
      MICs at 24 h by the Alamar colorimetric method is a valid alternate method for
      testing amphotericin B, fluconazole, and flucytosine against Candida species but
      not for testing fluconazole against C. tropicalis and T. glabrata. For
      flucytosine, much better agreement can be demonstrated against Candida species
      and T. glabrata at the 48-h readings by the Alamar method. Excellent agreement
      within +/- dilution can also be observed for amphotericin B, fluconazole, and
      flucytosine (80, 96, and 96%, respectively) against c. neoformans when the MICs
      were determined at 72 h by the Alamar method.

PMID- 8567902
TI  - Detection of Theileria annulata in blood samples of carrier cattle by PCR.
AB  - We report the detection of Theileria annulata, the causative agent of tropical
      theileriosis, by PCR in blood samples obtained from carrier cattle. The assay
      employs primers specific for the gene encoding the 30-kDa major merozoite surface
      antigen of T. annulata. A 721-bp fragment was amplified from blood samples taken
      monthly from calves experimentally infected with one of four different stocks of
      T. annulata originating in either Mauritania, Portugal, Spain, or Turkey. At the
      end of the experiment, five animals carried the infection for 12 months and two
      animals remained infected for 15 months. DNAs from six other Theileria species,
      T. parva, T. mutans, T. sergenti, T. buffeli, T. velifera, and T. taurotragi,
      were not amplified. Moreover, DNAs from four other hemoparasites (Anaplasma
      centrale, Anaplasma marginale, Babesia bovis, and Babesia bigemina) were also not
      amplified. As a control, primers derived from the small subunit rRNA gene of
      Theileria spp. amplified a 1.1-kb DNA fragment from all Theileria species
      examined but not from the other four hemoparasites. As few as two to three
      parasites per microliter of infected blood in a 50-microliters sample volume were
      detected by Southern or microplate hybridization with a T. annulata-specific cDNA
      probe. In addition, 92 field samples obtained from cattle in Spain were tested;
      22% were positive in blood smears, 40% were positive by immunofluorescent
      antibody test, and 75% were positive for T. annulata by PCR. The method provides
      a useful diagnostic tool for detecting T. annulata carrier cattle.

PMID- 8567903
TI  - Cervical lymphadenitis caused by a fastidious mycobacterium closely related to
      Mycobacterium genavense in an apparently immunocompetent woman: diagnosis by
      culture-free microbiological methods.
AB  - Fastidious mycobacteria usually infect immunocompromised hosts (human
      immunodeficiency virus-infected or otherwise immunosuppressed patients). We here
      describe severe lymphadenitis, caused by a fastidious mycobacterium closely
      related to Mycobacterium genavense, in an apparently immunocompetent woman, whose
      brother had died from an unidentified mycobacterial infection in 1969. A variety
      of techniques, including inoculation of nude mice, histopathology, electron
      microscopy, lipid analysis, ATP measurements, and molecular biology, were used to
      characterize this mycobacterium. All attempts to culture the etiological agent on
      many different media failed. The organism multiplied only in congenitally athymic
      nude mice. Although phenotypically similar to M. genavense, the mycobacterium
      differs from M. genavense by three nucleotides of the 16S rRNA gene sequence.
      Various antimycobacterial drugs were administered, including gamma interferon,
      but multiple relapses occurred. Finally, therapy with a combined regimen of
      clarithromycin, clofazimine, rifabutin, and ethambutol was curative. To our
      knowledge, this is the first report of lymphadenitis in an apparently
      immunocompetent patient, caused by a noncultivable Mycobacterium sp. closely
      related to M. genavense. This study emphasizes the importance of employing a
      variety of diagnostic approaches such as the inoculation of laboratory animals,
      histopathology, electron microscopy, lipid analysis, ATP measurements, and
      molecular biology to characterize novel microorganisms that cannot be cultured in
      vitro.

PMID- 8567904
TI  - Nonradioactive colony lift-hybridization assay for detection of Bordetella
      bronchiseptica infection in swine.
AB  - Current methods for the isolation and identification of Bordetella bronchiseptica
      from clinical samples are time-consuming and are based, in part, on subjective
      observations. We describe the use of a Bordetella-specific DNA probe in a
      nonradioactive colony lift-hybridization assay for the identification of B.
      bronchiseptica. Eleven of 82 clinical specimens were found to contain B.
      bronchiseptica by this method, while only 5 of these were reported to contain the
      organism when the specimens were analyzed by traditional methods. The chromosomal
      fragment containing a sequence complementary to the probe appeared to be
      conserved in B. bronchiseptica isolates from swine from a variety of sources. The
      assay is more rapid than culture and biochemical testing since it can be
      performed directly on primary culture plates, even when they are heavily
      contaminated with other bacterial species. Only minimal training is required to
      accomplish the assay successfully, and the results are easy to interpret.

PMID- 8567905
TI  - Analysis and comparison of plasmid profiles of Borrelia burgdorferi sensu lato
      strains.
AB  - The relationship between plasmid profiles and genospecies of the Lyme disease
      borreliae was investigated by using 40 strains from diverse biological and
      geographical sources. The genospecies of the strains were determined by
      examination of rRNA gene restriction patterns with cDNA probes complementary to
      the 16S and 23S rRNAs of Escherichia coli. Plasmid profiles were obtained by
      pulsed-field gel electrophoresis. The number of plasmids per strain and the size
      of these plasmids ranged from 4 to 10 and from 13.3 to 57.7 kb, respectively. The
      strains all contained a single large plasmid of 50 to 57.7 kb, with the exception
      of two Borrelia garinii strains that contained two or three of the large
      plasmids. The large plasmids of Borrelia burgdorferi sensu stricto strains ranged
      in size from 51.4 to 52.7 kb and were consistently smaller than the 54.0- to 57.7
      kb plasmids present in B. garinii and Borrelia afzelii. The exceptions of this
      observation were the two B. garinii strains with multiple large plasmids; in this
      case the large plasmids were 50.6 to 53 kb. Although a large degree of
      heterogeneity in the sizes and frequencies of occurrence of smaller plasmids was
      observed, there were some differences among the three genospecies. The
      differences in plasmids were further studied by using two BamHI DNA fragments
      from a 28.7-kb plasmid of B. burgdorferi sensu stricto 297 as probes. Both probes
      hybridized with the 27- to 29-kb plasmids of B. burgdorferi sensu stricto
      strains. In contrast, two patterns of hybridization were observed with B. garinii
      and B. afzelii. One pattern was the hybridization of both probes, with each probe
      hybridizing with a different plasmid. The other pattern was the hybridization of
      a plasmid of a strain with only one of the two probes. some strains of the three
      genospecies did not hybridize with either probe. Our results suggest that the
      plasmid profiles of B. burgdorferi sensu lato have genospecies characteristics
      and that the hybridization patterns of similar-sized plasmids are different for
      the three genospecies.

PMID- 8567906
TI  - Detection and identification of Mycobacterium tuberculosis directly from sputum
      sediments by Amplicor PCR.
AB  - Sputum specimens received for the diagnosis of tuberculosis or other
      mycobacterial infections were tested by a PCR-based assay and culture techniques.
      Results of the PCR assay (Amplicor Mycobacterium tuberculosis Test) were compared
      with results of standard culture techniques with cultures held for 6 weeks. One
      thousand nine specimens were included: 301 retrospective specimens (frozen at -70
      degrees C and later tested by PCR) and 708 prospective specimens (tested within 1
      day of processing). One hundred sixty-two (16%) of the specimens were culture
      positive for M. tuberculosis; 83 (51%) of these were also fluorochrome stain
      positive. The sensitivity and specificity of the Amplicor PCR compared with those
      of culture were 83% (134 of 162 specimens) and 97% (800 of 827 specimens),
      respectively. The sensitivity for fluorochrome stain-positive specimens was 99%,
      and that for fluorochrome stain-negative specimens was 66%. The great majority of
      the 28 PCR-negative, culture-positive specimens were low positives; 27 were smear
      negative and 19 contained < 100 CFU of M. tuberculosis per ml. The 27 PCR
      positive, culture-negative specimens included 24 that were positive by repeat
      testing by alternate primer PCR and were from patients with tuberculosis on
      antimicrobial therapy. With these considered culture misses, the final
      sensitivities of PCR and culture were 85, and 87%, respectively, while the
      specificities were 99.6 and 100%, respectively. After normal laboratory
      processing of sputum specimens, the Amplicor PCR assay can be completed in 8 h.
      Thus, it is possible to have results available within 10 h of specimen
      submission.

PMID- 8567907
TI  - Fatal cerebral mycoses caused by the ascomycete Chaetomium strumarium.
AB  - Three cases of fatal cerebral mycosis in males with prior histories of
      intravenous drug use from the United States and Australia are reported. Infection
      in each case was limited to brain abscess; no other sites of infection were
      observed. The fungus seen by histopathology and isolated from the brain tissue in
      each case was identified as Chaetomium strumarium. This is the first report of
      human infection by this species, and C. strumarium is the second species of
      Chaetomium known to cause primary brain infection. Chaetomium strumarium is
      unusual among members of the genus Chaetomium in forming ascocarps covered with
      pale, thin-walled, flexuous hairs, a feature leading to its original placement in
      the genus Achaetomium. Presence of pinkish exudate droplets and/or crystals
      associated with hyphae or ascocarps, sometimes accompanied by a pinkish
      diffusible pigment; good growth at 42 degrees C; and production of small conidia
      further distinguish this species. The brain abscess isolates were compared with
      isolates from prior cases of cerebral infection which had been identified as
      either Chaetomium atrobrunneum or Chaetomium globosum. With reidentification of
      one isolate originally identified as C. globosum to C. atrobrunneum, only C.
      strumarium and C. atrobrunneum have been confirmed to cause infection involving
      the brain.

PMID- 8567908
TI  - Diagnostic value of an amplification method (Gen-Probe) compared with that of
      culture for diagnosis of tuberculosis.
AB  - Five hundred fifty respiratory and nonrespiratory specimens from 340 patients
      were analyzed by comparing the Gen-Probe Amplified Mycobacterium Tuberculosis
      Direct Test (MTD) with conventional culture, which was the method of reference,
      for the detection of the Mycobacterium tuberculosis complex. After resolution of
      discrepant results by retesting the samples and reviewing the patients' clinical
      histories, a total of 60 respiratory specimens were MTD and culture positive, 347
      were MTD and culture negative, 4 were MTD positive and culture negative, and 1
      was MTD negative and culture positive. This results in a sensitivity of 98.4%, a
      specificity of 98.9%, and positive and negative predictive values of 93.8 and
      99.7%, respectively. Repeatedly, clinicians asked to test specimens of
      nonpulmonary origin by MTD. Although, MTD is not approved for use with
      nonrespiratory specimens, the following results were shown. Sixty-one pleural
      exudate specimens showed disappointing results (sensitivity, 20%). However, MTD
      performed well with another 77 nonrespiratory specimens; 17 samples were positive
      and 57 samples were negative by both MTD and culture. No false-negative results
      were found by MTD. Three MTD-positive, culture-negative specimens had high sample
      relative light unit/cutoff relative light unit ratios, strongly suggesting true
      tuberculosis. Positive microscopy and positive culture with MTD-negative results
      occurred 12 times. Those cultures showed atypical mycobacteria 11 times and
      Actinomyces species once. The stability of the reagents in the MTD kit was also
      assessed by testing reagents, including the enzyme mixture, kept at -70 degrees C
      for at least 6 months. No loss of activity was seen.

PMID- 8567909
TI  - Identification of "Streptococcus milleri" group isolates to the species level
      with a commercially available rapid test system.
AB  - Clinical isolates of the "Streptococcus milleri" species group were examined by
      conventional methods and a rapid, commercially available method for the
      identification of these strains to the species level. The levels of agreement
      between the identifications obtained with the commercially available system (Fluo
      Card Milleri; KEY Scientific, Round Rock, Tex.) and conventional methods were 98%
      for 50 Streptococcus anginosus strains, 97% for 31 Streptococcus constellatus
      strains, and 88% for 17 isolates identified as Streptococcus intermedius. Patient
      records were also studied in order to gain information on the frequency and sites
      of isolation of each of the three "S. milleri" group species.

PMID- 8567910
TI  - Association between alpha-hemolysin production and HeLa cell-detaching activity
      in fecal isolates of Escherichia coli.
AB  - Escherichia coli isolates that cause detachment of cell monolayers during in
      vitro adherence assays (cell-detaching E. coli [CDEC]) were recently reported as
      a potential new group of enteropathogenic bacteria. In the present study, 269 E.
      coli isolates from feces of children 1 to 5 years of age were identified as CDEC
      in a detaching assay developed with HeLa cells. The great majority of these
      isolates were hemolytic within 3 h of growth on blood agar plates and hybridized
      with a DNA probe for alpha-hemolysin (93.7%), while most of the non-detaching
      isolates were hemolytic within 24 h (3.6%) or nonhemolytic (94.8%). E. coli
      isolates that produced alpha-hemolysin were found in 60 (30%) of 200 children
      with diarrhea and 47 (24%) of 200 age-matched controls. No statistical
      significance was found for the differences in alpha-hemolysin production among
      the matched pairs (P = 0.2). These data suggest that CDEC isolates are not
      associated with diarrhea in the population studied.

PMID- 8567911
TI  - Hemocytic rickettsia-like organisms in ticks: serologic reactivity with antisera
      to Ehrlichiae and detection of DNA of agent of human granulocytic ehrlichiosis by
      PCR.
AB  - Ixodid ticks were collected from Connecticut, Massachusetts, Missouri,
      Pennsylvania, Rhode Island, and British Columbia (Canada) during 1991 to 1994 to
      determine the prevalence of infection with hemocytic (blood cell), rickettsia
      like organisms. Hemolymph obtained from these ticks was analyzed by direct and
      indirect fluorescent antibody (FA) staining methods with dog, horse, or human
      sera containing antibodies to Ehrlichia canis, Ehrlichia equi, or Rickettsia
      rickettsii. Of the 693 nymphal and adult Amblyomma americanum, Dermacentor
      variabilis, Ixodes scapularis, and Ixodes pacificus ticks tested with dog anti-E.
      canis antiserum, 209 (32.5%) contained hemocytic bacteria. The prevalence of
      infected ticks varied greatly with species and locale. In parallel tests of
      duplicate hemolymph preparations from adult I. scapularis ticks, the hemocytic
      organisms reacted positively with E. canis and/or E. equi antisera, including
      sera from persons who had granulocytic ehrlichiosis. In separate PCR analyses,
      DNA of the agent of human granulocytic ehrlichiosis was detected in 59 (50.0%) of
      118 adult and in 1 of 2 nymphal I. scapularis ticks tested from Connecticut.
      There was no evidence of Ehrlichia chaffeensis DNA in these ticks. In indirect FA
      tests of hemolymph for spotted fever group rickettsiae, the overall prevalence of
      infection was less than 4%. Specificity tests of antigens and antisera used in
      these studies revealed no cross-reactivity between E. canis and E. equi or
      between any of the ehrlichial reagents and those of R. rickettsii. The geographic
      distribution of hemocytic microorganisms with shared antigens to Ehrlichia
      species or spotted fever group rickettsiae is widespread.

PMID- 8567912
TI  - Characterization of Vibrio cgolerae non-O1 serogroups obtained from an outbreak
      of diarrhea in Lima, Peru.
AB  - In February 1994, an outbreak of diarrhea caused by non-O1 Vibrio cholerae
      occurred among volunteers in a vaccine trial study area in Lima, Peru.
      Clinically, 95% of the patients presented with liquid diarrhea with either no or
      mild dehydration. Serogrouping of 58 isolates recovered from diarrheal patients
      affected in the outbreak revealed seven different serogroups, with serogroups O10
      (21%) and O12 (65%) being predominant. Most of these isolates were susceptible to
      a variety of antimicrobial agents. None of the 58 isolates hybridized with a DNA
      probe previously used to detect the gene encoding the heat-stable enterotoxin NAG
      ST or produced cholera toxin as assessed by GM1 ganglioside enzyme-linked
      immunosorbent assay. Ribotyping exhibited 10 different BglI ribotype patterns
      among the 58 V. cholera non-O1 strains studied. However, ribotyping showed that
      all isolates belonging to serogroup O12 exhibited identical ribotypes and that
      83% of the serogroup O10 isolates belonged to another identical ribotype, thus
      showing excellent correlation between ribotypes and serogroups. Among a group of
      O10 and O12 isolates selected for virulence studies, none produced enterotoxin
      whereas the majority produced a cytotoxin, as assessed in Y1 and HeLa cells.
      These isolates were also negative for the gene encoding zonula occludens toxin
      (Zot) as assessed by a PCR assay. The isolates tested showed strong adherence and
      some degree of invasion in the HEp-2 cell assay, whereas none of the isolates was
      positive in the PCR assay for the gene encoding the toxin coregulated pilus
      subunit A antigen (tcpA). In the removable intestinal tie adult rabbit diarrhea
      model, O10 and O12 serogroup isolates produced severe diarrhea and occasionally
      death when rabbits were challenged with 10(10) bacterial cells. Fluid
      accumulation was shown in the rabbit intestinal loop test when whole cultures
      were injected. No significant difference in virulence was shown between serogroup
      O10 and O12 isolates. This study provides further evidence that V. chlorae non-O1
      non-O139 strains have diarrhegenic potential for humans through a yet-undefined
      mechanism(s) and that such strains can cause outbreaks.

PMID- 8567913
TI  - Comparison of MIDI Sherlock system and pulsed-field gel electrophoresis in
      characterizing strains of methicillin-resistant Staphylococcus aureus from a
      recent hospital outbreak.
AB  - An outbreak of methicillin-resistant Staphylococcus aureus infections at the
      University of Utah Health Sciences Center occurred over a 7-month period. While
      the isolates phenotypically appeared to be similar in gross morphology and have
      similar Vitek antibiotic susceptibility patterns, two additional methods of
      strain characterization were evaluated to enhance the epidemiological
      investigation: pulsed-field gel electrophoresis and gas chromatography with the
      MIDI Sherlock system. Sherlock uses gas chromatography to qualitatively and
      quantitatively analyze the cellular fatty acid composition of organisms and
      creates two-dimensional plots based on principal-component analysis to define
      groups of closely related organisms. All isolates were also evaluated by
      digesting their chromosomal DNAs with the low-frequency-cutting enzyme SmaI and
      separating the restriction fragments by contour-clamped homogeneous electric
      field gel electrophoresis. Sample preparation for this pulsed-field gel
      electrophoresis included a novel cell lysis procedure involving achromopeptidase,
      greatly reducing the turnaround time. Isolates tested were recovered from the
      following: 45 suspected outbreak patients, 6 hospitalized patients believed to be
      unrelated to the outbreak, 6 patients from outside the hospital, and one health
      care practitioner implicated in the outbreak. Of 45 phenotypically similar
      suspect strains, 43 clustered tightly on the Sherlock two-dimensional plot. All
      outbreak patient isolates were also identical by pulsed-field gel electrophoresis
      with the exception of the same two outliers identified by Sherlock. In this
      epidemiologic investigation, we found an excellent correlation between the
      Sherlock and pulsed-field gel electrophoresis results for strain characterization
      of methicillin-resistant S. aureus.

PMID- 8567914
TI  - Adenovirus types 2, 8, and 37 associated with genital infections in patients
      attending a sexually transmitted disease clinic.
AB  - Adenoviruses (Ads) are an important cause of respiratory illness, conjunctivitis,
      and gastroenteritis, but they are seldom recognized as a potential cause of
      sexually transmitted disease. We performed virus cultures on approximately 7,000
      patients attending a sexually transmitted disease clinic or other health
      department clinics for the evaluation of genital ulcers, urethritis, or
      conjunctivitis. Ads were isolated from genital or conjunctival specimens obtained
      from 23 (0.33%) patients. Among the 20 Ad-positive men, 15 (75%) had urethritis,
      12 (60%) had conjunctivitis, and 10 (50%) had both. All three Ad-positive women
      had vaginal discharge and genital ulcers or fissures. Ad isolates from 17
      patients were available for serotyping. Ad type 37 was isolated from 14 patients,
      Ad type 8 was isolated from 2 patients, and Ad type 2 was isolated from 1
      patient. In three of the Ad type 37 cases, Ad was recovered from both urethral
      and conjunctival specimens. One of the Ad type 8 cases had conjunctivitis, but
      the Ad type 2 case did not. Ads, particularly type 37, may be a sexually
      transmissible cause of genital ulcers, urethritis, and conjunctivitis.

PMID- 8567915
TI  - Fluconazole- and itraconazole-resistant Candida albicans strains from AIDS
      patients: multilocus enzyme electrophoresis analysis and antifungal
      susceptibilities.
AB  - Multilocus enzyme electrophoresis and in vitro susceptibility testing with a
      broth microdilution method were used to analyze Candida albicans strain diversity
      in four AIDS patients with recurrent oropharyngeal candidiasis who successively
      developed clinical resistance to fluconazole (FCZ) and itraconazole (ITZ). One to
      ten colonies per sample were randomly chosen from oral washings collected before
      the initial FCZ treatment and just before every other antifungal treatment; a
      total of 98 isolates were analyzed. Multilocus enzyme electrophoresis analysis
      revealed 14 different electrophoretic types (ETs). Statistical analysis of
      genetic distances showed that C. albicans isolates clustered into five
      subpopulations (I to V). In each subpopulation, isolates are closely related, and
      genetic distances between subpopulations I to IV are short. In contrast,
      subpopulation V, which contained isolates typed as ET8 and ET14, is strongly
      divergent from the others; these isolates may represent atypical C. albicans
      isolates. Only one patient was infected with a single strain during the course of
      azole therapy; for the three remaining patients, variants of the same strain and
      different strains were concurrently isolated. Clinical FCZ resistance was clearly
      correlated with in vitro data for three patients. Moreover, MICs of ITZ increased
      during FCZ therapy, and MICs of ITZ which were > or = 1.56 micrograms/ml were
      found when clinical ITZ resistance occurred; isolates from subpopulation V showed
      the highest MICs of ITZ. Because of the emergence of clinical ITZ resistance
      after clinical FCZ resistance, the feasibility of long-term azole therapy for
      mucosal candidiasis in AIDS patients is questioned.

PMID- 8567916
TI  - Genomic and proteinic characterization of strain S, a rickettsia isolated from
      Rhipicephalus sanguineus ticks in Armenia.
AB  - Strain S, a spotted fever group (SFG) rickettsia isolated from Rhipicephalus
      sanguineus ticks collected in Armenia, was identified. Microimmunofluorescence,
      sodium dodecyl sulfate-polyacrylamide gel protein electrophoresis and Western
      immunoblotting, PCR and then restriction fragment length polymorphism analysis,
      pulsed-field gel electrophoresis, and 16S rRNA gene sequencing were used to
      compare strain S with reference isolates. Strain S was found to possess
      proteinic, antigenic, and genomic patterns which were unique among SFG
      rickettsiae. Strain S is characterized by its high degree of pathogenicity for
      experimental animals, but its role as a potential human pathogen should be
      determined. The role of R. sanguineus ticks in the epidemiology of SFG
      rickettsiae is discussed.

PMID- 8567917
TI  - Sera from OspA-vaccinated dogs, but not those from tick-infected dogs, inhibit in
      vitro growth of Borrelia burgdorferi.
AB  - Dogs were challenged with Borrelia burgdorferi by exposure to ticks, with or
      without prior protection from infection by recombinant OspA (rOspA) vaccination.
      Sera from these dogs were tested for their capability to inhibit the growth of B.
      burgdorferi in vitro. Bacterial growth was detected by a color change in the
      culture medium, and the optical density was measured with a spectrophotometer in
      microtiter plates. By growth inhibition, which was complement dependent, the
      color change was lacking after 5 days of incubation. Over a 1-year study,
      nonvaccinated dogs infected by exposure to ticks showed high antibody titers to
      B. burgdorferi by kinetic enzyme-linked immunosorbent assay (KELA). The same sera
      did not inhibit spirochetal growth or did so only at a low dilution. These
      results corresponded to the lack of OspA and OspB antibodies seen in Western
      blots (immunoblots), and these dogs were not protected from infection or disease.
      In contrast, dogs immunized with rOspA prior to challenge with infected ticks
      produced high antibody titers, as determined by KELA, but their sera also had
      high growth-inhibiting antibody titers. Western blot analysis showed a strong
      band in the 32-kDa region when the sera of these dogs were tested. When adjuvant
      was administered with rOspA, antibody titers by both KELA and growth inhibition
      were higher and persisted longer in the immunized dogs. All dogs immunized with
      rOspA were protected from infection and disease.

PMID- 8567918
TI  - Diagnosis of Helicobacter pylori infection by PCR: comparison with other invasive
      techniques and detection of cagA gene in gastric biopsy specimens.
AB  - A PCR assay for the detection of Helicobacter pylori in gastric biopsy specimens
      with specific primers for ureC gene amplification (herein referred to as ureC
      PCR) was compared with other routine invasive methods (culture, the rapid-urease
      test, and Giemsa staining of histological sections) with samples from a group of
      104 consecutive dyspeptic patients. Bacteria were found in 40 (38.5%), 38
      (36.5%), 36 (34.6%), and 35 (33.7%) of the patients by ureC PCR, culture, the
      rapid-urease test, and Giemsa stain, respectively. Sixty-three patients had
      negative cultures, negative histological examinations, and negative rapid-urease
      test results, and 61 of these patients were also negative by ureC PCR. ureC PCR
      detected H. pylori in two culture-negative patients. In parallel, a PCR-based
      assay to detect the H. pylori cytotoxin-associated antigen (cagA) gene, a
      putative virulence gene, was also developed. To assess the likelihood of
      detection of H. pylori genes directly from gastric biopsy samples and from the
      corresponding H. pylori isolates, specimens from 31 patients were subjected to
      PCR with ureC- and cagA-targeting primers. All 31 biopsy specimens and the
      corresponding H. pylori isolates were positive in the ureC PCR. H. pylori strains
      that were cagA positive also gave positive cagA PCR fragments with biopsy
      specimens from the same patients. All ureC PCR-positive patients were examined;
      biopsy specimens from 10 of 11 (91.7%) duodenal ulcer patients harbored H. pylori
      cagA-positive strains, whereas 19 of26 (73%) of those from patients with chronic
      gastritis only were found to be cagA positive. These findings indicate first that
      ureC PCR is at least as sensitive as culture for diagnosing H. pylori infection
      and second that the presence of the H. pylori cagA gene can also be detected
      directly in biopsy specimens by PCR amplification.

PMID- 8567919
TI  - Recovery of Mycobacterium avium from cigarettes.
AB  - Mycobacterium avium was recovered from tobacco, cigarette paper, and cigarette
      filters. M. avium could also be recovered from cigarette filters after the
      cigarettes had been smoked.

PMID- 8567920
TI  - Six newly recognized types of Streptococcus pneumoniae.
AB  - The serological properties of six new pneumococcal capsular types are described.
      A table listing all 90 pneumococcal types and their cross-reactions is included.

PMID- 8567921
TI  - Phenolic acridine orange fluorescent stain for mycobacteria.
AB  - A new fluorescence acid-fast staining method with acridine orange as the specific
      stain is presented. Only two reagents are required: the acridine orange-specific
      stain and a destaining-counterstaining reagent. Compared with auramine
      fluorescence acid-fast staining, there was less nonspecific staining of non-acid
      fast debris which fluoresced a pale green contrasting color to provide a
      background in which to search for the red-to-orange fluorescing acid-fast
      bacilli. The results of the study indicate that the acridine orange method is
      superior to the auramine method in detecting acid-fast bacilli in specimen
      smears.

PMID- 8567922
TI  - Improved PCR detection of Chlamydia trachomatis by using an altered method of
      specimen transport and high-quality endocervical specimens.
AB  - Duplicate endocervical swabs were collected for detection of Chlamydia
      trachomatis by PCR (Roche Diagnostics). One swab was swirled in Specimen
      Transport Medium (Roche) for PCR testing and discarded. A saline aliquot from the
      other specimen, sent as a dry swab to the laboratory, was Papanicolaou stained to
      determine specimen adequacy, and the remainder was PCR tested. Significantly more
      (24%) PCR-positive results (118 versus 95; P < 0.001) were obtained with the dry
      specimens than with the swirled specimens when first tested. In addition, PCR
      positive results were obtained with 107 (10.6%) of 1,007 microscopically adequate
      specimens but with only 3 (0.9%) of 341 inadequate specimens (P < 0.001).

PMID- 8567923
TI  - Nocardia species as an etiologic agent in Parkinson's disease: serological
      testing in a case-control study.
AB  - To test the hypothesis that Nocardia spp. may be an etiologic factor in
      Parkinson's disease (PD), we used a serodiagnostic panel to determine if PD
      patients had antibodies specific for Nocardia spp. To validate the serological
      test panel, sera from healthy volunteers and from patients with culture-proven
      nocardiosis (n = 307) were compared in part 1 of the study. The sensitivity of
      the panel was 88% for detection of culture-proven nocardial infections, and
      specificity was 85% (excluding cross-reactive leprosy cases). In part 2, no
      difference in seropositivity was found when PD patients were compared with their
      age- and gender-matched controls (n = 140). We found a high exposure rate of
      humans to nocardial antigens, especially among men and older individuals. Our
      results offer no support to the hypothesis that Nocardia spp. are causative in
      PD; however, it is possible that serological testing may not be optimal for
      detection of nocardial central nervous system infection.

PMID- 8567924
TI  - Vancomycin-dependent Enterococcus faecium isolated from stool following oral
      vancomycin therapy.
AB  - The isolation of clinical strains of enterococci requiring vancomycin for growth
      has only recently been reported. We describe the isolation of Enterococcus
      faecium requiring vancomycin for growth from the stool of a patient who had
      completed oral vancomycin therapy. Growth of the vancomycin-dependent E. faecium
      was supported by ristocetin and D-alanyl-D-alanine but not by daptomycin,
      teicoplanin, or D,L-alanine. Spontaneous revertants not requiring vancomycin
      occurred at a rate of 1 in 10(6). Both the vancomycin-dependent E. faecium and
      the revertant hybridized with a vanB gene probe and had identical contour-clamped
      homogeneous electrophoresis patterns. The majority of revertant colonies were
      resistant to teicoplanin, suggesting constitutive production of the vanB ligase.
      We believe the vancomycin-dependent E. faecium evolved from a vancomycin
      resistant, vancomycin-independent E. faecium in the presence of high
      concentrations of vancomycin in the intestine.

PMID- 8567925
TI  - Cutaneous phaeohyphomycosis caused by Alternaria longipes in an immunosuppressed
      patient.
AB  - Alternaria longipes was reported as the agent of a cutaneous infection in a
      patient with a neoplastic disease. The fungus has not been reported previously as
      causing disease in humans. It was distinguished by its rather small conidia with
      smooth or slightly verruculose walls and a pale brown beak which rarely extended
      into a secondary conidiophore. In vitro inhibitory activities of amphotericin B,
      ketoconazole, itraconazole, and miconazole were shown.

PMID- 8567926
TI  - Nonisotopic hybridization assay for determination of relative amounts of
      genotypic human immunodeficiency virus type 1 zidovudine resistance.
AB  - A nonisotopic hybridization assay for human immunodeficiency virus genotypic
      zidovudine resistance determination is described. Biotinylated PCR product was
      hybridized with enzyme-labeled probes for wild-type or resistant mutant sequences
      and detected colorimetrically or chemiluminescently in a microplate format.
      Changes in mutant-to-wild-type ratios allow for the monitoring of longitudinal
      patient samples.

PMID- 8567927
TI  - Partial nucleotide sequencing of six subtype 2c hepatitis C viruses detected in
      Italy.
AB  - The great majority of 121 hepatitis C virus (HCV) isolates obtained from 117
      Italian patients with community-acquired infection could readily be typed by
      genotype-specific PCR. Subtype 1b was dominant (74 isolates); subtypes 2b, 2a,
      and 1a followed, with 19, 14, and 8 isolates, respectively. The six isolates that
      remained untyped by this method were classified as subtype 2c on the basis of
      sequence analysis of PCR amplicors obtained from the core and NS5 genes. These
      findings indicate that HCV subtype 2c has a relatively high prevalence in Italy.
      Sequencing the core region from positions 160 to 259 is sufficient to distinguish
      subtype 2c from other known HCV genotypes.

PMID- 8567928
TI  - Comparison of six different PCR methods for detection of Pneumocystis carinii.
AB  - We have recently developed a nested PCR method which amplifies internal
      transcribed spacers (ITS) of the ribosomal RNA genes of Pneumocystis carinii. To
      determine whether this PCR method can be used to diagnose P. carinii infections,
      we examined 30 bronchoalveolar lavage (BAL) specimens that were shown
      microscopically to contain P. carinii organisms by the P. carinii ITS PCR (Pc-ITS
      PCR) and five other PCR methods that have been described for detecting P. carinii
      in clinical specimens. The targets of these PCR methods are portions of 18S rRNA,
      mitochondrial (mt) rRNA, 5S rRNA, thymidylate synthase (TS), and dihydrofolate
      reductase (DHFR). We also examined five different fungi, including Saccharomyces
      cerevisiae, Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans,
      and Aspergillus fumigatus to determine the specificity of these six PCR methods
      for P. carinii. All 30 BAL specimens were positive by both the Pc-ITS-PCR and the
      18S rRNA gene PCR, whereas only 26 (87%), 18 (60%), 10 (33%), and 7 (23%) of 30
      BAL specimens were positive by mt rRNA gene PCR, TS gene PCR, 5S rRNA gene PCR,
      and DHFR gene PCR, respectively. Although the 18S rRNA gene PCR had the same
      sensitivity as the Pc-ITS-PCR, it nonspecifically amplified S. cerevisiae and C.
      albicans. The TS gene PCR also produced false-positive PCR results with C.
      albicans and C. neoformans. None of the other PCR methods (Pc-ITS-PCR, mt rRNA
      gene, 5S rRNA gene, and DHFR gene PCR) amplified the control fungal DNA.
      Considering both sensitivity and specificity, we conclude that Pc-ITS-PCR is the
      most effective of the six PCR methods evaluated in this study for the detection
      of P. carinii in BAL specimens.

PMID- 8567929
TI  - Distribution of serotypes of Streptococcus pneumoniae isolated from invasive
      infections over a 16-year period in the greater Sao Paulo area, Brazil.
AB  - Capsular types of pneumococci from normally sterile body sites of 1,622 patients
      in Brazil were analyzed. Of 1,477 isolates from cerebrospinal fluid, 76.1% were
      of types represented in the currently available pneumococcal vaccine. The
      importance of age, time, and place in determining the optimal formulation of
      pneumococcal vaccine is considered.

PMID- 8567930
TI  - Utility of direct immunofluorescence and virus culture for detection of varicella
      zoster virus in skin lesions.
AB  - A direct immunofluorescence assay (DFA) with a monoclonal antibody from Ortho
      Diagnostic Systems was compared with conventional cell culture for the rapid
      detection of varicella-zoster virus (VZV) in 140 dermal lesions from 133
      patients. A total of 79 (56%) specimens were positive for VZV: 40 (51%) by DFA
      alone, 2 (3%) by culture only, and 37 (47%) by both culture and DFA. After
      discordant analysis, the sensitivities and negative predictive values,
      respectively, were 97.5% (77 of 79) and 96.8% (61 of 63) for DFA and 49.4% (39 of
      79) and 60.4% (61 of 101) for viral culture. Of the 39 positive viral cultures,
      VZV was isolated from 38 (97%) cultures in A549 cells, 23 (59%) in primary rhesus
      monkey kidney cells, and only 16 (41%) in MRC-5 cells. We conclude that DFA is
      the optimal method for rapid identification of VZV. In addition, better recovery
      of VZV in culture may be achieved by using A549 cells.

PMID- 8567931
TI  - Mycoleptodiscus indicus: a new etiologic agent of phaeohyphomycosis.
AB  - Mycoleptodiscus indicus, a dematiaceous hyphomycete, was identified as the causal
      agent of subcutaneous infection in the knee of a 72-year-old male gardener
      residing in coastal South Carolina. The patient had Wegener's granulomatosis and
      immunodeficiency. Synovial fluid and biopsy tissue sections from the prepatellar
      bursa stained with hematoxylin and eosin, periodic acid-Schiff, and Gomori
      methenamine silver stains revealed branched, septate hyphae and many moniliform
      hyphal elements. When tissue sections were stained by the Fontana-Masson
      procedure, melanin pigment in the hyphal cell walls and at the septa was evident.
      A velvety, dematiaceous mold was isolated from both synovial fluid and the biopsy
      tissue. Sporulation was induced by exposure of slide cultures on potato dextrose
      agar to UV light for 12 h at 25 degrees C followed by incubation of the slide
      cultures at 25 degrees C in the dark for 4 weeks. Clypeate sporodochia consisting
      of ampulliform, compressed, phialidic conidiogenous cells produced curved,
      hyaline, one-celled conidia with setulae at one or both ends. Initial treatment
      with fluconazole for 7 days was not effective, and cultures were positive after
      treatment. Treatment with amphotericin B with concomitant irrigation and
      debridement of the affected area followed by treatment with itraconazole resulted
      in resolution of the infection.

PMID- 8567932
TI  - Recovery of Helicobacter pylori from gastric biopsy specimens is not dependent on
      the transport medium used.
AB  - The survival of six clinical isolates of Helicobacter pylori at room temperature
      was investigated after suspension in five different media: brucella broth with 5%
      lysed horse blood (BBLH), phosphate-buffered saline (PBS), 20% glucose, Stuart
      medium, and PBS with 10% Fildes enrichment (PBS-F). Only in BBLH and PBS-F no
      decrease in mean bacterial numbers was observed during the 24-h study period. No
      H. pylori isolates could be cultured from Stuart medium after 7 h of incubation.
      In contrast, the recovery rates in PBS-F or Stuart medium of H. pylori isolates
      from gastric tissue specimens collected from 19 H. pylori-positive patients were
      not significantly different even after a delay of culture of up to 24 h. Our data
      show that the medium composition is not critical for the survival of H. pylori
      within gastric tissue specimens.

PMID- 8567933
TI  - Discrimination of Mycobacterium tuberculosis strains by PCR.

PMID- 8567935
TI  - Survival of embryonic cardiac myocytes transplanted into host rat soleus muscle.
AB  - Small fragments of embryonic hearts were transplanted either alongside or into a
      skeletal muscle (soleus) of an adult host. The implanted tissue grew, and
      survived for at least 6 months after transplantation. The graft was well
      vascularized and established a network of blood vessels that communicated with
      the host's circulation. This communication appeared to be established by the
      proliferation of blood vessels from the graft into the host tissues. The grafted
      tissue was rhythmically active and the rate of these contractions was similar to
      that of adult rat hearts. The frequency of the spontaneous contractions could be
      modified by acetylcholine. Exposure to acetylcholine lead to a reversible slowing
      of the rate of beating. The presence of gap junctions in the transplanted tissue
      was revealed by visualizing connexin 43 with a specific antibody. During early
      periods after grafting the gap junctions were scattered within the graft but over
      time they became aligned into rows, to prepare for the formation of intercalated
      discs. Thus embryonic heart grafted into, or alongside skeletal muscle is able to
      acquire a considerable degree of differentiation.

PMID- 8567934
TI  - Co-expression in CHO cells of two muscle proteins involved in excitation
      contraction coupling.
AB  - Ryanodine receptors and dihydropyridine receptors are located opposite each other
      at the junctions between sarcoplasmic reticulum and either the surface membrane
      or the transverse tubules in skeletal muscle. Ryanodine receptors are the calcium
      release channels of the sarcoplasmic reticulum and their cytoplasmic domains form
      the feet, connecting sarcoplasmic reticulum to transverse tubules.
      Dihydropyridine receptors are L-type calcium channels that act as the voltage
      sensors of excitation-contraction coupling: they sense surface membrane and
      transverse tubule depolarization and induce opening of the sarcoplasmic reticulum
      release channels. In skeletal muscle, ryanodine receptors are arranged in
      extensive arrays and dihydropyridine receptors are grouped into tetrads, which in
      turn are associated with the four subunits of ryanodine receptors. The
      disposition allows for a direct interaction between the two sets of molecules.
      CHO cells were stably transformed with plasmids for skeletal muscle ryanodine
      receptors and either the skeletal dihydropyridine receptor, or a skeletal-cardiac
      dihydropyridine receptor chimera (CSk3) which can functionally substitute for the
      skeletal dihydropyridine receptor, in addition to plasmids for the alpha 2, beta
      and gamma subunits. RNA blot hybridization gave positive results for all
      components. Immunoblots, ryanodine binding, electron microscopy and exposure to
      caffeine show that the expressed ryanodine receptors forms functional tetrameric
      channels, which are correctly inserted into the endoplasmic reticulum membrane,
      and form extensive arrays with the same spacings as in skeletal muscle. Since
      formation of arrays does not require coexpression of dihydropyridine receptors,
      we conclude that self-aggregation is an independent property of ryanodine
      receptors. All dihydropyridine receptor-expressing clones show high affinity
      binding for dihydropyridine and immunolabelling with antibodies against
      dihydropyridine receptor. The presence of calcium currents with fast kinetics and
      immunolabelling for dihydropyridine receptors in the surface membrane of CSk3
      clones indicate that CSk3-dihydropyridine receptors are appropriately targeted to
      the cell's plasmalemma. The expressed skeletal-type dihydropyridine receptors,
      however, remain mostly located within perinuclear membranes. In cells
      coexpressing functional dihydropyridine receptors and ryanodine receptors, no
      junctions between feet-bearing endoplasmic reticulum elements and surface
      membrane are formed, and dihydropyridine receptors do not assemble into tetrads.
      A separation between dihydropyridine receptors and ryanodine receptors is not
      unique to CHO cells, but is found also in cardiac muscle, in muscles of
      invertebrates and, under certain conditions, in skeletal muscle. We suggest that
      failure to form junctions in co-transfected CHO cell may be due to lack of an
      essential protein necessary either for the initial docking of the endoplasmic
      reticulum to the surface membrane or for maintaining the interaction between
      dihydropyridine receptors and ryanodine receptors. We also conclude that
      formation of tetrads requires a close interaction between dihydropyridine
      receptors and ryanodine receptors.

PMID- 8567936
TI  - Essential light chain of Drosophila nonmuscle myosin II.
AB  - We have cloned and sequenced a cDNA encoding the essential (alkaline) light chain
      of nonmuscle myosin from Drosophila melanogaster. The protein predicted from the
      cDNA matches partial amino acid sequence derived from essential light chain
      protein that copurifies with native nonmuscle myosin heavy chain. This completes
      the sequence of the three myosin subunits, two of which have been shown
      genetically to be required for morphogenesis and cytokinesis (the heavy chain
      encoded by zipper and the regulatory light chain encoded by spaghetti squash).
      The essential light chain protein is 147 amino acids in length and is 53%
      identical to human smooth muscle essential light chain. The sequence is
      consistent with the presence of four helix-loop-helix domains seen in
      crystallographic structures of the striated muscle myosin light chains and their
      close relative, calmodulin. We identified the most conserved residues among
      essential light chain sequences from multiple phyla and present their locations
      on the crystallographic structure of striated muscle essential light chain. This
      highlights several conserved contacts among the myosin subunits that may be
      important for the structure and regulation of the myosin motor. The gene encoding
      Drosophila nonmuscle essential light chain (Mlc-c) localizes to cytological
      position 5A6 and we discuss prospects for genetic analysis in this region.

PMID- 8567937
TI  - Determination of resting free calcium in barnacle muscle using modified
      aequorins, buffered calcium injections, and simultaneous image-intensified video
      microscopy.
AB  - Knowing the resting free calcium is important in understanding the role of
      calcium as an intracellular second messenger. We used a bracketing (null)
      technique with a luminescent calcium indicator, aequorin, microinjection and
      image-intensification to measure free calcium in single muscle fibres from the
      barnacle, Balanus nubilus. We injected modified aequorins (recombinant, and hch-)
      which after a 30 min diffusion gave reasonable resting glows. Subsequent
      injection of calcium (strongly buffered with either EGTA or BAPTA, 10 mM)
      increased or decreased the resting glow depending on the free calcium level in
      the injected buffer solution. This bracketing (null) method is inherently
      accurate, but mechanical artifacts on calcium injection reduce the accuracy when
      total light emission is measured. We therefore used image-intensified video
      microscopy of the injected region and video processing (Image-1) of artifact-free
      regions, to greatly improve the consistency. The luminescence in a pre-selected
      region of the muscle fibre was measured as a function of time during the
      injection. Solution calciums were chosen so that if the first injection decreased
      the resting glow, the second increased it, or vice versa, thus bracketing the
      true resting value. We used two methods to determine the true value bracketed by
      our injections: (1) a linear interpolation using the fractional changes in
      luminescence or (2) a power law interpolation assuming a 2.2 or 2.5 power
      relationship between luminescence and free calcium. Using these methods, we
      estimated the free calcium level in the lateral depressor fibres of freshly
      dredged barnacles to be 279 +/- 36 nM (+/- SD), 339 +/- 42 nM, or 352 +/- 45 nM
      for the linear, 2.2 and 2.5 powers respectively under the conditions of hch
      aequorin and BAPTA buffers (using a K'Ca for BAPTA of 3.0 x 10(6) M-1 for our
      conditions). Recombinant-aequorin gave essentially the same result while EGTA
      buffers yielded a somewhat higher value but because of influences of pH on the
      K'Ca for EGTA (taken as 6.7 x 10(6) M-1 for our conditions) was considered less
      reliable. Minor changes in [Mg2+] upon buffer injection can lead to
      underestimates of the true resting [Ca2+] by at most 10%. Thus, we estimate the
      resting free calcium in barnacle muscle fibres to be 300-380 nM.

PMID- 8567938
TI  - Flexation of caldesmon: effect of conformation on the properties of caldesmon.
AB  - The contribution of the extended and bent forms of caldesmon to its function was
      investigated by examining chemically modified forms of this protein. The bent
      'hairpin' form of caldesmon was enhanced between pH 6.0 and 8.0 and at low ionic
      strengths, as reported by an increase in excimer fluorescence of pyrene-labelled
      caldesmon under these conditions. The presence of nucleotides also produced
      significant conformational changes in caldesmon, as detected by fluorescence
      measurements and protease digestions. Titrations of pyrene caldesmon with actin,
      heavy meromyosin, and calmodulin resulted in a decrease in excimer fluorescence.
      The function of the bent form of caldesmon was investigated by using
      intramolecular 1-ethyl-3-(3-dimethylamino propyl) carbodiimide-crosslinked
      caldesmon. The inhibition of acto-S-1 ATPase activity by crosslinked caldesmon
      was less efficient compared with that by pyrene modified and control caldesmons.
      Caldesmon's ability to switch from an activator to an inhibitor of actin
      activated ATPase of myosin was also affected by the folding. Cosedimentation
      experiments revealed normal binding of crosslinked caldesmon to smooth muscle
      myosin. These results indicate the importance of caldesmon's transition from
      extended to folded forms and suggest possible functional roles for these
      different forms of caldesmon.

PMID- 8567939
TI  - The afterdepolarization in Rana temporaria muscle fibres following osmotic shock.
AB  - Rana temporaria sartorius muscle fibres were exposed to varied sequences of
      solution and temperature changes that have been employed hitherto in procedures
      that sought to decouple the transverse tubules from the surface membrane. The
      incidence of such detubulation was assessed in large numbers of fibres through
      demonstrating a loss or otherwise of the after-depolarization that normally
      reflects successful tubular propagation of the surface action potential. This
      criterion yielded assessments of the existing detubulation techniques in
      agreement with earlier results. The experiments then developed an improved
      detubulation procedure that required only brief (15 min) exposures to glycerol,
      its replacement in a single step by a Ca2+/Mg(2+)-Ringer solution for 30 min, and
      rapid cooling from room temperature (19-21 degrees C) to 6-10 degrees C prior to
      final restoration of the normal Ringer solution. This sequence of steps yielded
      an optimal incidence (98%) of detubulation in viable surface fibres that were
      amenable to electrophysiological studies. Studies that systematically modified
      the detubulation procedure demonstrated that the omission of any one step in the
      protocol significantly reduced the incidence of detubulation with or without
      accompanying deteriorations in fibre resting potentials. Successful detubulation
      accordingly required an initial exposure to an optimal glycerol concentration
      that lasted for a minimal duration and for its abrupt withdrawal. Inclusion of a
      cooling step within 30 min after glycerol withdrawal was coincident with, and
      critical to, optimal tubular isolation. Thus, cooling steps that either preceded,
      or that followed the glycerol withdrawal step by more than 60 min, resulted in a
      sharp reduction in the incidence of detubulation. Similarly, a critical period of
      exposure to Ca2+/Mg2+ Ringer solution also promoted detubulation without
      compromising the recovery of stable and satisfactory resting potentials. The
      findings reported here remain consistent with a primarily osmotic mechanism for
      detubulation. However, they demonstrated additional and important influences of
      temperature and of divalent cation concentration on the extent of tubular
      detachment when such factors were modified during the time course of the expected
      volume changes that followed each adjustment in osmotic condition.

PMID- 8567940
TI  - Dihydropyridine receptors in transverse tubules from normal and dystrophic
      chicken skeletal muscle.
AB  - Calcium overload is a fundamental pathogenic event associated with chronic muscle
      degeneration in muscular dystrophies. The possibility that L-type voltage
      dependent calcium channels were involved in the etiology of chicken muscular
      dystrophy was investigated by studying the dihydropyridine receptors in
      transverse tubule membranes isolated from skeletal muscle of normal (line 412)
      and dystrophic (line 413) chickens. The yield of T-tubular protein from
      dystrophic muscle was considerably increased compared with that from normal
      muscle (2.51 +/- 0.18 vs 1.04 +/- 0.31 mg protein x 100 g muscle-1). The binding
      of the calcium channel antagonist (+) [3H]PN200-110 to the dihydropyridine
      receptor in transverse tubule preparations was relatively slow, markedly affected
      by temperature and required divalent cations. (+) [3H]PN200-110 equilibrium
      binding assays revealed a single class of high-affinity sites and showed that
      maximum binding capacity (Bmax) (3.17 +/- 0.47 for normal and 3.51 +/- 0.52 pmol
      x mg protein-1 for dystrophic transverse tubules) and dissociation constant (Kd)
      (0.32 +/- 0.07 and 0.26 +/- 0.09 nM, respectively) were not significantly
      different in normal and dystrophic membranes. Kinetic studies indicated that
      normal and dystrophic transverse tubules did not differ significantly in
      association (2.54 x 10(6) and 2.27 x 10(6) M(-1)s(-1), respectively) and
      dissociation (8.5 x 10(-4) and 9.3 x 10(-4)s(-1), respectively) rate constants.
      Since dissociation kinetics for both preparations were monoexponential under all
      the experimental conditions employed, no low-affinity binding sites for (+)
      [3H]PN200-110 could be detected in chicken transverse tubules membranes. However,
      immunoblot assay, using a monoclonal antibody, revealed that dystrophic
      transverse tubules as compared with normal membranes were enriched twofold with
      the alpha 1-subunit of the dihydropyridine receptor. Therefore, although
      dihydropyridine-binding sites were not altered in transverse tubule membranes
      from dystrophic chicken skeletal muscle, both the increased yield in T-tubule
      vesicles and the enhanced immunodetection of the alpha 1-subunit of the
      dihydropyridine receptor, suggest that total content in dihydropyridine receptor
      is higher in dystrophic than in normal muscle.

PMID- 8567941
TI  - Actin interaction with purified dystrophin from electric organ of Torpedo
      marmorata: possible resemblance with filamin-actin interface.
AB  - We have purified dystrophin from Torpedo marmorata electric tissue by means of
      alkaline extraction in conjunction with an affinity chromatography column using
      anti-peptide antibodies. Using solution (cosedimentation) and solid phase
      experiments (sedimentation with Sepharose filamentous actin and ELISA), we have
      demonstrated that purified dystrophin is able to bind filamentous and monomeric
      actin. Using ELISA coupled with biotin labelled peptides and taking advantage of
      strong affinity binding of streptavidin-biotin complex, we have identified two
      exposed sequences of the actin molecule implicated in dystrophin binding:
      fragment 40-113, further restricted to peptide 75-106 and peptide 360-372. In a
      previous study, we have shown that fragment 40-113 displays binding site(s) for
      filamin but probably not for alpha-actinin. Moreover, we have recently reported
      that alpha-actinin and filamin display divergent behaviours towards
      conformational changes of actin. In this study, we have demonstrated that,
      similarly to filamin, dystrophin binding is insensitive to the locking of actin
      in a monomeric conformation. Taken together, these results lead us to favour the
      idea that dystrophin could share properties in common with filamin in its binding
      of actin.

PMID- 8567942
TI  - Visualization of the subsarcolemmal cytoskeleton network of mouse skeletal muscle
      cells by en face views and application to immunoelectron localization of
      dystrophin.
AB  - The ultrastructural organization of the highly interconnected filamentous network
      underneath the sarcolemma as well as the role played by the muscle protein
      dystrophin within this cytoskeleton remain yet unclear. More accurate information
      has been obtained by using a method which provides three-dimensional en face
      views of large membrane areas applied to mouse cultured myotubes and isolated
      adult skeletal muscle fibres. Two levels have been distinguished in the
      cytoskeleton underlying the sarcolemma: the submembranous level, partly
      integrated into the membrane, and the cortical level, invading the proximal
      cytoplasmic space. Few differences have been found between the membrane
      cytoskeletons of myotubes issued from 14-day-old cultures and those of adult
      fibres. The comparison was done with cells where dystrophin is missing (mdx mouse
      muscle): surprisingly, the lack of dystrophin does not induce obvious or dramatic
      ultrastructural disorganization, either in the cortical cytoskeletal network or
      in the submembranous one. Immunogold labelling of either the central-rod or the C
      terminal domain of dystrophin is not located among the cortical network. This
      study provides additional data on the spatial ordering of subsarcolemmal
      cytoskeletal elements: dystrophin does not appear as a filamentous structure
      entirely located among subsarcolemmal cytoskeleton but seems partly embedded in
      membranous material.

PMID- 8567943
TI  - Muscle System Workshop and 36th Annual Drosophila Research Conference, Atlanta,
      Georgia, 5-9 April 1995.

PMID- 8567944
TI  - Probing the depths of degradation: matrix metalloproteinase-2 and endometrial
      menstrual breakdown.

PMID- 8567945
TI  - Biological insights through genomics: mouse to man.

PMID- 8567946
TI  - Role of transiently altered sarcolemmal membrane permeability and basic
      fibroblast growth factor release in the hypertrophic response of adult rat
      ventricular myocytes to increased mechanical activity in vitro.
AB  - One of the trophic factors that has been implicated in initiating or facilitating
      growth in response to increased mechanical stress in several tissues and cell
      types is basic fibroblast growth factor (bFGF; FGF-2). Although mammalian cardiac
      muscle cells express bFGF, it is not known whether it plays a role in mediating
      cardiac adaptation to increased load, nor how release of the cytosolic 18-kD
      isoform of bFGF would be regulated in response to increased mechanical stress. To
      test the hypothesis that increased mechanical activity induces transient
      alterations in sarcolemmal permeability that allow cytosolic bFGF to be released
      and subsequently to act as an autocrine and paracrine growth stimulus, we
      examined primary isolates of adult rat ventricular myocytes maintained in serum
      free, defined medium that were continually paced at 3 Hz for up to 5 d. Paced
      myocytes, but not nonpaced control cells, exhibited a "hypertrophic" response,
      which was characterized by increases in the rate of phenylalanine incorporation,
      total cellular protein content, and cell size. These changes could be mimicked in
      control cells by exogenous recombinant bFGF and could be blocked in continually
      paced cells by a specific neutralizing anti-bFGF antibody. In addition, medium
      conditioned by continually paced myocytes contained significantly more bFGF
      measured by ELISA and more mitogenic activity for 3T3 cells, activity that could
      be reduced by a neutralizing anti-bFGF antibody. The hypothesis that transient
      membrane disruptions sufficient to allow release of cytosolic bFGF occur in paced
      myocytes was examined by monitoring the rate of uptake into myocytes from the
      medium of 10-kD dextran linked to fluorescein. Paced myocytes exhibited a
      significantly higher rate of fluoresceinlabeled dextran uptake. These data are
      consistent with the hypothesis that nonlethal, transient alterations in
      sarcolemmal membrane permeability with release of cytosolic bFGF is one mechanism
      by which increased mechanical activity could lead to a hypertrophic response in
      cardiac myocytes.

PMID- 8567947
TI  - Regulation of rat hepatic low density lipoprotein receptors. In vivo stimulation
      by growth hormone is not mediated by insulin-like growth factor I.
AB  - Growth hormone (GH) has an important role in the regulation of hepatic LDL
      receptor expression and plasma lipoprotein levels. This investigation was
      undertaken to evaluate if these effects of GH on hepatic LDL receptors are direct
      or mediated by insulin-like growth factor I (IGF-I). Two models were studied in
      which substitution with GH is important for the regulation of hepatic LDL
      receptors: hypophysectomized rats receiving high-dose ethynylestradiol or
      challenge with dietary cholesterol. The hypophysectomized rats were hormonally
      substituted by infusion with dexamethasone and L-thyroxine, and either GH or IGF
      I. In both models, GH was essential for maintaining normal expression of LDL
      receptors. In contrast, despite fully normalized plasma levels, IGF-I did not
      support the expression of hepatic LDL receptors. Analysis of plasma lipoproteins
      revealed that substitution with GH, but not with IGF-I, reduced LDL and
      intermediate density lipoproteins. In addition, determination of hepatic mRNA
      levels for apo B-100 and apo B-48 indicated that GH may be more effective than
      IGF-I in the promotion of apo B mRNA editing. In conclusion, GH has specific
      effects on hepatic LDL receptor expression and plasma lipoprotein levels that are
      not mediated by IGF-I.

PMID- 8567948
TI  - Insulin-like growth factor-1 is a potent neuronal rescue agent after hypoxic
      ischemic injury in fetal lambs.
AB  - This study was designed to determine the potential of IGF-1 as a neuronal rescue
      agent after cerebral ischemia. Unanesthetized late gestation fetal sheep were
      subjected to 30-min cerebral ischemia by inflation of carotid artery occluder
      cuffs. 2 h later either 0.1 microgram rhIGF-1, 1 microgram rhIGF-1, 10 micrograms
      rhIGF-1, or vehicle was infused into a lateral cerebral ventricle over 1 h.
      Histologic outcome was assessed 5 d later. Overall neuronal loss was reduced with
      0.1 microgram (P < 0.05) and 1 microgram (P < 0.002) rhIGF-1, but treatment with
      10 micrograms was not effective. With 1 microgram rhIGF-1 neuronal loss scores
      were significantly lower in brain regions examined including cortex, hippocampus,
      and striatum, whereas with 0.1 microgram rhIGF-1 the parietal cortex and thalamus
      were not improved and the improvement seen in other regions was less than with 1
      microgram rhIGF-1. Treatment with 1 microgram rhIGF-1 also delayed the onset of
      seizures and reduced their incidence. Moreover, the secondary phase of cytotoxic
      edema was reduced and delayed in onset. We conclude that low dose rhIGF-1 therapy
      promotes neuronal rescue after cerebral hypoxic-ischemic injury in utero, but the
      effect is dose dependent. Importantly, rhIGF-1 is effective and nontoxic when
      administered 2 h after the hypoxic ischemic insult. This distinguishes IGF-1 from
      most other neuroprotective therapies and suggests clinical application may be
      possible.

PMID- 8567949
TI  - Recombinant interferon-alpha selectively inhibits the production of interleukin-5
      by human CD4+ T cells.
AB  - The effects of recombinant IFN-alpha on the production of IL-5 by human CD4+ T
      cells were first analyzed on resting CD4+ T cells purified from normal PBMC and
      stimulated either with a combination of PMA and anti-CD28 mAb or anti-CD3 mAb
      cross-linked on B7-1/CD32-transfected mouse fibroblasts. We found that IFN-alpha
      profoundly inhibited in a dose-dependent manner IL-5 production by resting CD4+ T
      cells whereas IL-10 was upregulated in both systems. The addition of a
      neutralizing anti-IL-10 mAb to PMA and anti-CD28 mAb upregulated IL-5 production
      by resting CD4+ T cells but did not prevent IFN-alpha-induced IL-5 inhibition. We
      then analyzed the effect of IFN-alpha on the production of cytokines by
      differentiated type 2 helper (Th2) CD4+CD3- cells isolated from peripheral blood
      of two patients with the hypereosinophilic syndrome. In both cases, IFN-alpha
      markedly inhibited IL-5 production while it induced mild upregulation of IL-4 and
      IL-10. Finally, the inhibitory effect of IFN-alpha on IL-5 production was
      confirmed on a panel of Th2 and Th0 clones generated in vitro. In 2 out of 6
      clones, IL-5 inhibition was associated with upregulation of IL-4 and IL-10. We
      conclude that IFN-alpha selectively downregulates IL-5 synthesis by human CD4+ T
      cells.

PMID- 8567950
TI  - Functional expression of Fas and Fas ligand on human gut lamina propria T
      lymphocytes. A potential role for the acidic sphingomyelinase pathway in normal
      immunoregulation.
AB  - The expression and function of Fas (CD95/APO-1), a cell surface receptor directly
      responsible for triggering cell death by apoptosis, was investigated on human T
      lymphocytes resident within the intestinal lamina propria, a major site of
      antigen challenge and persistent lymphocyte activation. Three color
      immunofluorescence and FACS analysis indicated that virtually all freshly
      isolated human gut lamina propria T lymphocytes (T-LPL) express Fas, together
      with the marker of progress activation CD45R0. A discrete fraction of freshly
      isolated T-LPL also constitutively expressed Fas ligand (FasL), perhaps as a
      result of recent in vivo activation. Importantly, whereas Fas cross-linking did
      not result in apoptosis induction in peripheral blood T lymphocytes (T-PBL), Fas
      was found to be fully effective in generating the apoptotic signal in T-LPL. This
      was associated with the activation of an acidic sphingomyelinase and with
      ceramide generation, early events known to be involved in Fas-mediated apoptotic
      signaling. By contrast, acidic sphingomyelinase activation and ceramide
      production were not detectable in T-PBL after Fas cross-linking. However C2
      ceramide, a cell permeant synthetic analog of ceramide, could efficiently induce
      apoptosis in T-LPL and T-PBL when added exogenously. These data indicate that T
      LPL constitutively express both Fas and FasL and that Fas cross-linking generates
      signals resulting in sphingomyelin hydrolysis and apoptosis, outlining a
      potential mechanism involved in intestinal tolerance. Moreover, they provide the
      first evidence of a role for ceramide-mediated pathways in normal
      immunoregulation.

PMID- 8567951
TI  - Dynamics of viral replication in infants with vertically acquired human
      immunodeficiency virus type 1 infection.
AB  - About one-third of vertically HIV-1 infected infants develop AIDS within the
      first months of life; the remainder show slower disease progression. We
      investigated the relationship between the pattern of HIV-1 replication early in
      life and disease outcome in eleven infected infants sequentially studied from
      birth. Viral load in cells and plasma was measured by highly sensitive
      competitive PCR-based methods. Although all infants showed an increase in the
      indices of viral replication within their first weeks of life, three distinct
      patterns emerged: (a) a rapid increase in plasma viral RNA and cell-associated
      proviral DNA during the first 4-6 wk, reaching high steady state levels (> 1,000
      HIV-1 copies/10(5) PBMC and > 1,000,000 RNA copies/ml plasma) within 2-3 mo of
      age; (b) a similar initial rapid increase in viral load, followed by a 2.5-50
      fold decline in viral levels; (c) a significantly lower (> 10-fold) viral
      increase during the first 4-6 wk of age. All infants displaying the first pattern
      developed early AIDS, while infants with slower clinical progression exhibited
      the second or third pattern. These findings demonstrate that the pattern of viral
      replication and clearance in the first 2-3 mo of life is strictly correlated
      with, and predictive of disease evolution in vertically infected infants.

PMID- 8567952
TI  - Antigen targeting to myeloid-specific human Fc gamma RI/CD64 triggers enhanced
      antibody responses in transgenic mice.
AB  - Besides their phagocytic effector functions, myeloid cells have an essential role
      as accessory cells in the induction of optimal humoral immune responses by
      presenting captured antigens and activating lymphocytes. Antigen presentation by
      human monocytes was recently found to be enhanced in vitro through the high
      affinity Fc receptor for IgG (Fc gamma RI; CD64), which is exclusively present on
      myeloid cells. To evaluate a comparable role of Fc gamma RI in antigen
      presentation in vivo, we generated human Fc gamma RI transgenic mice. Under
      control of its endogenous promoter, human Fc gamma RI was selectively expressed
      on murine myeloid cells at physiological expression levels. As in humans,
      expression was properly regulated by the cytokines IFN-gamma, G-CSF, IL-4, and IL
      10, and was up-regulated during inflammation. The human receptor expressed by
      murine macrophages bound monomeric human IgG and mediated particle phagocytosis
      and IgG complex internalization. To evaluate whether specific targeting of
      antigens to Fc gamma RI can induce enhanced antibody responses, mice were
      immunized with an anti-human Fc gamma RI antibody containing antigenic
      determinants. Transgenic mice produced antigen-specific antibody responses with
      high IgG1 titers and substantial IgG2a and IgG2b responses. These data
      demonstrate that human Fc gamma RI on myeloid cells is highly active in mediating
      enhanced antigen presentation in vivo, and show that anti-Fc gamma RI mAbs are
      promising vaccine adjuvants.

PMID- 8567953
TI  - Energy-ubiquitin-dependent muscle proteolysis during sepsis in rats is regulated
      by glucocorticoids.
AB  - Recent studies suggest that sepsis-induced increase in muscle proteolysis mainly
      reflects energy-ubiquitin-dependent protein breakdown. We tested the hypothesis
      that glucocorticoids activate the energy-ubiquitin-dependent proteolytic pathway
      in skeletal muscle during sepsis. Rats underwent induction of sepsis by cecal
      ligation and puncture or were sham-operated and muscle protein breakdown rates
      were measured 16 h later. The glucocorticoid receptor antagonist RU 38486 or
      vehicle was administered to groups of septic and sham-operated rats. In other
      experiments, dexamethasone (2.5 or 10 mg/kg) was injected subcutaneously in
      normal rats. Total and myofibrillar proteolysis was determined in incubated
      extensor digitorum longus muscles as release of tyrosine and 3-methylhistidine,
      respectively. Energy-dependent proteolysis was determined in incubated muscles
      depleted of energy with 2-deoxyglucose and 2,4-dinitrophenol. Levels of muscle
      ubiquitin mRNA and free and conjugated ubiquitin were determined by Northern and
      Western blot, respectively. RU 38486 inhibited the sepsis-induced increase in
      total and myofibrillar energy-dependent protein breakdown rates and blunted the
      increase in ubiquitin mRNA levels and free ubiquitin. Some, but not all, sepsis
      induced changes in ubiquitin protein conjugates were inhibited by RU 38486.
      Injection of dexamethasone in normal rats increased energy-dependent proteolysis
      and ubiquitin mRNA levels. The results suggest that glucocorticoids regulate the
      energy-ubiquitin-dependent proteolytic pathway in skeletal muscle during sepsis.

PMID- 8567954
TI  - Modifications of myelin basic protein in DM20 transgenic mice are similar to
      those in myelin basic protein from multiple sclerosis.
AB  - Transgenic mice containing different numbers of transgenes (2-70) of the myelin
      proteolipid protein DM20 were phenotypically normal up to 3 mo of age, after
      which the mice containing 70 copies of the transgene spontaneously demyelinated
      and died at 10-12 mo. Since we demonstrated that demyelination in multiple
      sclerosis involved specific chemical changes in myelin basic protein (MBP), we
      investigated the MBP in our transgenic line for similar changes. Both the total
      amount of MBP in brain and the MBP mRNA levels were unaffected at the different
      ages. All the isoforms (14-21 kD) of MBP were present, but the microheterogeneity
      (a posttranslational event) was changed resulting in a higher proportion of the
      less cationic components reminiscent of the changes in MBP found in multiple
      sclerosis. An increased amount of the citrullinated form of MBP was found by
      Western blot analysis. Immunogold labeling of cryosections of brain revealed a
      greater density of particles with the anticitrulline antibody at 10 mo and that
      the levels of peptidylarginine deiminase (which deiminates protein-bound arginine
      to citrulline) were increased. This stable transgenic line represents a useful
      animal model for the human disease multiple sclerosis.

PMID- 8567955
TI  - A novel Escherichia coli lipid A mutant that produces an antiinflammatory
      lipopolysaccharide.
AB  - A unique screen was used to identify mutations in Escherichia coli lipid A
      biosynthesis that result in a decreased ability to stimulate E-selectin
      expression by human endothelial cells. A mutation was identified in the msbB gene
      of E. coli that resulted in lipopolysaccharide (LPS) that lacks the myristoyl
      fatty acid moiety of the lipid A. Unlike all previously reported lipid A mutants,
      the msbB mutant was not conditionally lethal for growth. Viable cells or purified
      LPS from an msbB mutant had a 1000-10,000-fold reduction in the ability to
      stimulate E-selectin production by human endothelial cells and TNF alpha
      production by adherent monocytes. The cloned msbB gene was able to functionally
      complement the msbB mutant, restoring both the LPS to its native composition and
      the ability of the strain to stimulate immune cells. Nonmyristoylated LPS acted
      as an antagonist for E-selectin expression when mixed with LPS obtained from the
      parental strain. These studies demonstrate a significant role for the myristate
      component of LPS in immune cell activation and antagonism. In addition, the msbB
      mutant allowed us to directly examine the crucial role that the lipid A structure
      plays when viable bacteria are presented to host defense cells.

PMID- 8567956
TI  - Endothelin-3 induces hypertrophy of cardiomyocytes by the endogenous endothelin-1
      mediated mechanism.
AB  - We have recently reported that endothelin-1 (ET-1) mediates angiotensin II
      induced hypertrophy of cardiomyocytes as an autocrine/paracrine factor. In the
      present study, we examined whether endothelin-3 (ET-3) induces hypertrophy of
      cultured neonatal rat cardiomyocytes and whether endogenous ET-1 mediates this
      effect. ET-3 (10(-7) M) increased the cell surface area of cardiomyocytes after
      48 h. ET-3 dose dependently (10(-9)-10(-7) M) stimulated protein synthesis as
      evaluated by [3H]leucine incorporation; the maximum response was 1.4-fold
      increase over the control at 10(-7) M. Since the response of cardiac hypertrophy
      is characterized by enhanced expression of fetal isoforms of muscle specific
      genes, the effect of ET-3 on steady state levels of mRNA for skeletal alpha-actin
      was evaluated by Northern blot analysis. ET-3 (10(-9)-10(-7) M) increased mRNA
      level for skeletal alpha-actin with a maximum response after 6 h. ET-3-induced
      [3H]leucine incorporation, skeletal alpha-actin mRNA and cell surface area were
      inhibited by a synthetic ETB receptor antagonist (BQ788). Interestingly, ET-3
      induced skeletal alpha-actin gene expression and [3H]leucine incorporation were
      inhibited by a synthetic ETA receptor antagonist (BQ123) as well as by antisense
      oligonucleotides against peproET-1 mRNA. ET-3 (10(-7) M) transiently increased
      mRNA levels for ET-1 peaking at 30 min and stimulated the release of
      immunoreactive ET-1 from cardiomyocytes. These results suggest that endogenous ET
      1 locally generated and secreted by cardiomyocytes may contribute to ET-3-induced
      cardiac hypertrophy as an autocrine/paracrine factor.

PMID- 8567957
TI  - A nonsense mutation in the erythrocyte band 3 gene associated with decreased mRNA
      accumulation in a kindred with dominant hereditary spherocytosis.
AB  - We studied a French kindred with typical hereditary spherocytosis (HS). Studies
      of erythrocytes and erythrocyte membranes from HS individuals revealed abnormal
      erythrocyte membrane mechanical stability as well as 15-20% deficiency of band 3,
      the anion transporter. Anion transport studies of red cells from two affected
      individuals revealed decreased sulfate flux. Nucleotide sequence of cDNA encoding
      the distal third of the cytoplasmic domain and the entire transmembrane domain of
      band 3 obtained by RT-PCR of reticulocyte RNA of an affected family member was
      normal. Sequence analysis of genomic DNA from an HS individual identified a
      nonsense mutation of the band 3 gene, Q330X, near the end of the band 3
      cytoplasmic domain. This mutation was present in genomic DNA of all HS family
      members and absent in DNA of unaffected family members. Using an RT-PCR-based
      assay, a marked quantitative decrease in accumulation of the mutant band 3 RNA
      was detected. Thus the codon 330 nonsense mutation is responsible for the
      decreased accumulation of mutant band 3 RNA and the deficiency of band 3 protein
      in this kindred. These results have important implications for the role of band 3
      defects in the membrane pathobiology of HS as well as for the techniques used in
      detection of HS mutations.

PMID- 8567958
TI  - In vitro and in vivo effects of leukotriene B4 antagonism in a primate model of
      asthma.
AB  - To test the hypothesis that leukotriene (LT) B4 antagonists may be clinically
      useful in the treatment of asthma, CP-105,696 was evaluated in vitro, using
      chemotaxis and flow cytometry assays, and in vivo, using a primate asthma model.
      CP-105,696 inhibited LTB4-mediated monkey neutrophil chemotaxis (isolated cells,
      LTB4 = 5 nM) and CD11b upregulation (whole blood, LTB4 = 100 nM) with IC50 values
      of 20 nM and 16.5 microM, respectively. Using a modification of a previously
      described in vivo protocol (Turner et al. Am. J. Respir. Crit. Care Med. 1994.
      149: 1153-1159), we observed that treatment with CP-105,696 inhibited the acute
      increase in bronchoalveolar lavage (BAL) levels of IL-6 and IL-8 by 56.9 +/-
      13.2% and 46.9 +/- 14.5%, respectively, 4 h after challenge with Ascaris suum
      antigen (Ag). CP-105,696 tended to reduce the increase in BAL protein levels 0.5
      h after Ag challenge by 47.5 +/- 18.3%, but this was not statistically
      significant. In addition, CP-105,696 prevented the significant 11-fold increase
      in airway responsiveness to methacholine after multiple Ag challenge. These
      results suggest that LTB4 partially mediates acute and chronic responses to
      antigen in an experimental primate asthma model and support the clinical
      evaluation of LTB4 antagonists in human asthma.

PMID- 8567959
TI  - Regulation of transforming growth factor-beta 1 expression by the hepatitis B
      virus (HBV) X transactivator. Role in HBV pathogenesis.
AB  - TGF-beta 1 has been implicated in the pathogenesis of liver disease. The high
      frequency of detection of the hepatitis B virus X (HBx) antigen in liver cells
      from patients with chronic hepatitis, cirrhosis, and liver cancer suggested that
      expression of HBx and TGF-beta 1 may be associated. To test this possibility, we
      examined the expression of TGF-beta 1 in the liver of transgenic mice expressing
      the HBx gene. We show that the patterns of expression of TGF-beta 1 and Hbx
      protein are similar in these mice and that HBx activates transcription of the TGF
      beta 1 gene in transfected hepatoma cells. The cis-acting element within the TGF
      beta 1 gene that is responsive to regulation by Hbx is the binding site for the
      Egr family of transcription factors. We further show that the Egr-1 protein
      associates with the HBx protein, allowing HBx to participate in the
      transcriptional regulation of immediate-early genes. Our results suggest that
      expression of Hbx might induce expression of TGF-beta 1 in the early stages of
      infection and raise the possibility that TGF-beta 1 may play a role in hepatitis
      B virus pathogenesis.

PMID- 8567960
TI  - Bone mineralization in an osteogenesis imperfecta mouse model studied by small
      angle x-ray scattering.
AB  - We have studied the size and orientation of mineral crystals in cortical bone of
      oim/oim mice, which are known to produce only alpha 1(I) collagen homotrimers and
      which may serve as a model for human osteogenesis imperfecta. Long bones (femur
      and tibia) from young (5 wk old) oim/oim mice and from unaffected heterozygous
      counterparts were investigated by small-angle x-ray scattering (SAXS), which is
      sensitive to structures smaller than 50 nm. Mineral crystals were compared in
      terms of their thickness and their alignment with respect to the long bone axis.
      While electron microscopic tomography has recently shown the existence of large
      mineral blocks (with all dimensions typically exceeding 50 nm) in mineralized
      tendons of oim/oim mice, SAXS revealed a family of thin, possibly needle-like,
      crystals in cortical bone. These crystals were similar in shape to those observed
      previously in normal mice, but they were thinner and less well aligned in oim/oim
      mice relative to heterozygotes. Moreover, the crystal thickness and their
      alignment with the bone axis were more variable in oim/oim bone, with a close
      correlation (r = 0.94, P < 0.001) between the two parameters. The presence of
      smaller crystals with more variable alignment in corticalis of oim/oim mice may
      contribute to the brittleness of their bone, similar to that of human
      osteogenesis imperfecta.

PMID- 8567961
TI  - Thrombospondin-1, an inhibitor of angiogenesis, is regulated by progesterone in
      the human endometrium.
AB  - Thrombospondin-1 (TSP1), a multifunctional extracellular matrix glycoprotein, has
      been shown to suppress the angiogenic response in vivo and in vitro. We
      hypothesized that TSP1 might play a role in the inhibition of capillary
      morphogenesis during the endometrial cycle and examined its expression in 46
      human endometrial specimens. Our results show that the expression of TSP1 in the
      endometrium is (a) cycle-dependent, (b) associated with periods of low capillary
      growth, and (c) regulated by progesterone. TSP1 protein was identified in the
      basement membrane of capillaries of the functional endometrium during the
      secretory phase. Abundant expression of TSP1 mRNA in the secretory phase was also
      detected by in situ hybridization, in contrast to the low levels seen in the
      proliferative phase. These findings were confirmed by Northern analysis of
      proliferative and secretory endometrium. Transcripts for TSP1 were observed
      predominantly in stromal cells, but signal was also detected in some endothelial
      and smooth muscle cells. Since the proliferation of endometrial tissue is
      regulated by steroid hormones, we tested the effects of estrogen and progesterone
      on TSP1 expression by stromal cells isolated from human endometrium. We found
      that levels of TSP1 mRNA and protein were increased after incubation with
      progesterone. Maximal stimulation of mRNA was observed after 8 h of treatment
      with 10-50 microM progesterone, and the effect was suppressed by the progesterone
      antagonist RU-486. Induction by progesterone was cell-specific and equivalent to
      the stimulation mediated by PDGF. Finally, the levels of TSP1 present in
      progesterone-stimulated cultures were sufficient to inhibit the migration of
      endothelial cells in vitro; this effect was nullified by anti-TSP antibodies. We
      therefore propose that the production of TSP1 at later stages of the endometrial
      cycle is linked to the inhibition of vessel formation and that TSP1 expression is
      progesterone-dependent in this tissue.

PMID- 8567962
TI  - Agmatine, a bioactive metabolite of arginine. Production, degradation, and
      functional effects in the kidney of the rat.
AB  - Until recently, conversion of arginine to agmatine by arginine decarboxylase
      (ADC) was considered important only in plants and bacteria. In the following, we
      demonstrate ADC activity in the membrane-enriched fraction of brain, liver, and
      kidney cortex and medulla by radiochemical assay. Diamine oxidase, an enzyme
      shown here to metabolize agmatine, was localized by immunohistochemistry in
      kidney glomeruli and other nonrenal cells. Production of labeled agmatine,
      citrulline, and ornithine from [3H]arginine was demonstrated and endogenous
      agmatine levels (10(-6)M) in plasma ultrafiltrate and kidney were measured by
      HPLC. Microperfusion of agmatine into renal interstitium and into the urinary
      space of surface glomeruli of Wistar-Fromter rats produced reversible increases
      in nephron filtration rate (SNGFR) and absolute proximal reabsorption (APR).
      Renal denervation did not alter SNGFR effects but prevented APR changes.
      Yohimbine (an alpha 2 antagonist) microperfusion into the urinary space produced
      opposite effects to that of agmatine. Microperfusion of urinary space with BU-224
      (microM), a synthetic imidazoline2 (I2) agonist, duplicated agmatine effects on
      SNGFR but not APR whereas an I1 agonist had no effect. Agmatine effects on SNGFR
      and APR are not only dissociable but appear to be mediated by different
      mechanisms. The production and degradation of this biologically active substance
      derived from arginine constitutes a novel endogenous regulatory system in the
      kidney.

PMID- 8567963
TI  - Rhinovirus stimulation of interleukin-6 in vivo and in vitro. Evidence for
      nuclear factor kappa B-dependent transcriptional activation.
AB  - To further understand the biology of rhinovirus (RV), we determined whether IL-6
      was produced during RV infections and characterized the mechanism by which RV
      stimulates lung cell IL-6 production. In contrast to normals and minimally
      symptomatic volunteers, IL-6 was detected in the nasal washings from patients who
      developed colds after RV challenge. RV14 and RV1A, major and minor receptor group
      RVs, respectively, were potent stimulators of IL-6 protein production in vitro.
      These effects were associated with significant increases in IL-6 mRNA
      accumulation and gene transcription. RV was also a potent stimulator of IL-6
      promoter-driven luciferase activity. This stimulation was modestly decreased by
      mutation of the nuclear factor (NF)-IL-6 site and abrogated by mutation of the NF
      kappa B site in this promoter. An NF-kappa B-DNA binding activity, mediated by
      p65, p50, and p52 NF-kappa B moieties, was rapidly induced in RV-infected cells.
      Activator protein 1-DNA binding was not similarly altered. These studies
      demonstrate that IL-6 is produced during symptomatic RV infections, that RVs are
      potent stimulators of IL-6 elaboration, and that RV stimulation IL-6 production
      is mediated by an NF-kappa B-dependent transcriptional stimulation pathway. IL-6
      may play an important role in the pathogenesis of RV infection, and NF-kappa B
      activation is likely to be an important event in RV-induced pathologies.

PMID- 8567964
TI  - Detection of receptors for interleukin-6, interleukin-11, leukemia inhibitory
      factor, oncostatin M, and ciliary neurotrophic factor in bone marrow
      stromal/osteoblastic cells.
AB  - The functional receptor complexes assembled in response to interleukin-6 and -11
      (IL-6 and IL-11), leukemia inhibitory factor (LIF), oncostatin M (OSM), and
      ciliary neurotrophic factor (CNTF), all involve the signal transducer gp130: IL-6
      and IL-11 induce homodimerization of gp130, while the rest heterodimerize gp130
      with other gp130-related beta subunits. Some of these cytokines (IL-6, IL-11, and
      CNTF) also require a specificity-determining alpha subunit not directly involved
      in signaling. We have searched for functional receptor complexes for these
      cytokines in cells of the bone marrow stromal/osteoblastic lineage, using
      tyrosine phosphorylation of the beta subunits as a detection assay. Collectively,
      murine calvaria cells, bone marrow-derived murine cell lines (+/+LDA11 and
      MBA13.2), as well as murine (MC3T3-E1) and human (MG-63) osteoblast-like cell
      lines displayed all the previously recognized alpha and beta subunits of this
      family of receptors. However, individual cell types had different constellations
      of alpha and beta subunits. In addition and in difference to the other cell types
      examined, MC3T3-E1 cells expressed a heretofore unrecognized form of gp130; and
      MG-63 displayed an alternative form (type II) of the OSM receptor. These findings
      establish that stromal/osteoblastic cells are targets for the actions of all the
      members of the cytokine subfamily that shares the gp130 signal transducer; and
      suggest that different receptor repertoires may be expressed at different stages
      of differentiation of this lineage.

PMID- 8567965
TI  - Human endometrial matrix metalloproteinase-2, a putative menstrual proteinase.
      Hormonal regulation in cultured stromal cells and messenger RNA expression during
      the menstrual cycle.
AB  - Proteinases are likely effectors of endometrial menstrual breakdown. We have
      investigated proteinase production by human endometrial stromal cells subjected
      in vitro to progesterone (P) withdrawal, the physiologic stimulus for
      menstruation. Culture media of cells exposed to estradiol, P, or estradiol plus P
      had low levels of proteolytic activity similar to cultures maintained in the
      absence of steroids. P withdrawal, or addition of RU486 to P-treated cultures,
      stimulated proteinase secretion. The stromal cell proteinase was characterized by
      gelatin zymography, inhibitor profile, and organomercurial activation, as a
      metalloproteinase present mostly as a 66-kD proenzyme with lower levels of a 62
      kD active form. The P withdrawal-induced metalloproteinase was identified as
      matrix metalloproteinase-2 (MMP-2) by Western blotting. The increase of MMP-2
      induced by P withdrawal was associated with the metalloproteinase-dependent
      breakdown of stromal cultures, involving dissolution of extracellular matrix and
      dissociation of stromal cells. Northern analysis showed the differential
      expression of MMP-2 mRNA in late secretory phase endometrium. These findings are
      consistent with the involvement of stromal cell-derived MMP-2 in the proteolysis
      of extracellular matrix promoting cyclic endometrial breakdown and the onset of
      menstrual bleeding.

PMID- 8567966
TI  - Antisense oligodeoxynucleotides selectively suppress expression of the mutant
      alpha 2(I) collagen allele in type IV osteogenesis imperfecta fibroblasts. A
      molecular approach to therapeutics of dominant negative disorders.
AB  - We are investigating the use of antisense oligodeoxynucleotides to selectively
      suppress expression of the mutant type I collagen allele in osteogenesis
      imperfecta (OI). In this report, we target a human collagen mutation in its
      natural cellular context. We used cultured fibroblasts from a case of type IV OI,
      in which the mutant alpha 2(I) allele produces mRNA with exon 16 deleted due to a
      point mutation in the splice donor site. Lipid-mediated transfection was used to
      deliver antisense, sense and missense phosphorothioates targeted to both the
      abnormal mRNA exon 15/17 junction and the nuclear level point mutation.
      Significant suppression of the mutant protein chain and mRNA was achieved with
      antisense oligonucleotide to both mRNA and nuclear levels. Mutant protein was
      suppressed to 44-47% and mutant alpha 2(I) mRNA to 37-43% of their levels in
      control cells, indicating decreased mRNA as the basis for suppression.
      Selectivity of mutant allele suppression was better with an mRNA target:
      suppression was sequence specific and normal mRNA was expressed at 79% of its
      level in untreated cells. With a nuclear target, significant suppression of
      mutant mRNA occurred not only with antisense and sense, but also with missense
      oligonucleotide, which suppressed mutant mRNA to 60% of its level in untreated
      cells. We also investigated the time course of suppression of protein and mRNA in
      response to a 4 h transfection of antisense oligonucleotide. From 24-72 h after
      transfection, mutant protein was suppressed to approximately 50% of its untreated
      level and suppression of mutant message was significantly greater than that of
      normal message. The suppression achieved in these studies is insufficient for
      clinical intervention, but our results provide support for further development of
      antisense therapy as an approach to the treatment of dominant negative disorders.

PMID- 8567967
TI  - Hyperproinsulinemia is associated with increased beta cell demand after
      hemipancreatectomy in humans.
AB  - The cause of disproportionate hyperproinsulinemia in patients with type II
      diabetes is controversial. To examine whether increased beta cell demand might
      contribute, we measured proinsulin and insulin concentrations in clinically
      healthy humans who had undergone hemipancreatectomy for the purpose of organ
      donation, a procedure previously demonstrated to increase beta cell demand and
      diminish insulin secretory reserve capacity. Subjects were studied at least 1 yr
      after hemipancreatectomy. Seven donors were followed prospectively and serves as
      their own controls. Nine additional donors were matched with normal controls
      (cross-sectional group). Fasting serum concentrations of intact proinsulin and
      conversion intermediates (total) were measured by a two-step radioimmunoassay;
      independent determinations of intact proinsulin and 32,33 split proinsulin were
      performed using an immunoradiometric assay. Serum total proinsulin values were
      significantly greater in hemipancreatectomized groups than controls (prospective
      group: predonation = 6.24 +/- 1.14 pM, postdonation = 34.63 +/- 17.47 pM, P <
      0.005; cross-sectional group: controls = 5.78 +/- 1.12 pM, donors = 15.22 +/-
      5.20 pM, P < 0.025). The ratio of total proinsulin to immunoreactive insulin was
      directly correlated with fasting plasma glucose and showed a significant inverse
      relationship to secretory reserve capacity. Both absolute and relative
      hyperproinsulinemia is found in hemipancreatectomized donors. These data
      demonstrate that partial pancreatectomy with its associated increase in beta cell
      demand raises measures of proinsulin in humans.

PMID- 8567968
TI  - Oxysterols present in atherosclerotic tissue decrease the expression of
      lipoprotein lipase messenger RNA in human monocyte-derived macrophages.
AB  - The presence of oxysterols in macrophages isolated from atherosclerotic tissue
      and the effect of oxysterols on the regulation of lipoprotein lipase (LPL) mRNA
      were studied. Both rabbit and human macrophages, freshly isolated from
      atherosclerotic aorta, show about the same distribution of oxysterols, analyzed
      by isotope dilution mass spectrometry, except that all three preparations of
      human arterial-derived macrophages contained high levels of 27
      hydroxycholesterol, which was not found in rabbit macrophages. To determine if
      oxysterols regulate LPL expression, human monocyte-derived macrophages were
      incubated with different oxysterols. Incubation with 7 beta-hydroxycholesterol
      and 25-hydroxycholesterol resulted in a 70-75% reduction of LPL mRNA, analyzed by
      quantitative RT-PCR. Cholesterol and other tested oxysterols showed no effect on
      macrophage LPL mRNA expression compared with control. LPL activity in the medium
      was also reduced after exposure of the macrophages to 7 beta-hydroxycholesterol
      and 25-hydroxycholesterol. In conclusion, we have demonstrated accumulation of
      oxysterols in macrophage-derived foam cells isolated from atherosclerotic aorta.
      There was suppression of LPL mRNA in human monocyte-derived macrophages after
      incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol. It is
      tempting to suggest that an exposure to oxysterols may explain our earlier
      observation of a low level of LPL mRNA in arterial foam cells.

PMID- 8567969
TI  - Hypoxia-induced paracrine regulation of vascular endothelial growth factor
      receptor expression.
AB  - Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF), an
      endothelial cell (EC)-specific mitogen, stimulates angiogenesis in vivo,
      particularly in ischemic regions. VEGF/VPF expression by cells of hypoxic tissues
      coincides with expression of its two receptors, KDR and flt-1, by ECs in the same
      tissues. We investigated whether hypoxia or hypoxia-dependent conditions operate
      in coordinating this phenomenon. Human umbilical vein and microvascular ECs were
      exposed to direct hypoxia or to medium conditioned (CM) by myoblasts maintained
      in hypoxia for 4 d. Control ECs were maintained in normoxia or normoxia-CM.
      Binding of 125I-VEGF to ECs was then evaluated. Hypoxic treatment of ECs had no
      effect on 125I-VEGF binding. However, treatment of ECs with hypoxia-CM produced a
      threefold increase in 125I-VEGF binding, with peak at 24 h (P < 0.001, ANOVA).
      Scatchard analysis disclosed that increased binding was due to a 13-fold increase
      in KDR receptors/cell, with no change in KDR affinity (Kd = 260 +/- 51 pM,
      normoxia-CM versus Kd = 281 +/- 94 pM, hypoxia-CM) and no change in EC number
      (35.6 +/- 5.9 x 10(3) ECs/cm2, normoxia-CM versus 33.5 +/- 5.5 x 10(3) ECs/cm2,
      hypoxia-CM). Similar results were obtained using CM from hypoxic smooth muscle
      cells. KDR upregulation was not prevented by addition to the hypoxia-CM of
      neutralizing antibodies against VEGF, tumor necrosis factor-alpha, transforming
      growth factor beta 1 or basic fibroblast growth factor. Similarly, addition of
      VEGF or lactic acid to the normoxia-CM had no effect on VEGF binding. We conclude
      that mechanism(s) initiated by hypoxia can induce KDR receptor upregulation in
      ECs. Hypoxic cells, normal or neoplastic, not only can produce VEGF/VPF, but can
      also modulate its effects via paracrine induction of VEGF/VPF receptors in ECs.

PMID- 8567970
TI  - IgA class switch in I alpha exon-deficient mice. Role of germline transcription
      in class switch recombination.
AB  - Studies have implicated defective Ig class switch in the pathogenesis of IgA
      deficiency. To understand better the molecular events that regulate IgA class
      switch, a 1.4-kb region of the IgA locus containing the I alpha exon was replaced
      with a human hypoxanthine phosphoribosyltransferase minigene by gene targeting in
      murine embryonic stem cells. The I alpha exon-deficient mice derived from these
      embryonic stem cells had normal IgA levels in serum and secretions and normal
      numbers of IgA B cells in Peyer's patches and spleen. Further, I alpha exon
      deficient B cells efficiently underwent IgA class switch in vitro, despite the
      absence of I alpha exon-containing germline transcripts. Notably, I alpha exon
      deficient B cells did not require TGF-beta for IgA class switch since stimulation
      with LPS alone led to IgA expression. Nonetheless, whereas I alpha exon-deficient
      B cells constitutively expressed human hypoxanthine phosphoribosyltransferase
      transcripts, they did not produce IgA in the absence of LPS stimulation. These
      results demonstrate that the I alpha exon or transcripts containing the I alpha
      exon are not required for IgA class switch. Further, the effects of TGF-beta on I
      alpha locus transcription can be supplanted by expression of a heterologous
      minigene at that locus, but a second signal is required for the induction of IgA
      class switch.

PMID- 8567971
TI  - Murine V lambda x and V lambda x-containing antibodies bind human myelin basic
      protein.
AB  - Myelin basic protein (MBP) is highly immunogenic and a known autoantigen capable
      of inducing experimental allergic encephalomyelitis (EAE), the animal model of
      multiple sclerosis. We have previously described a murine monoclonal antibody
      (mAb), F28C4, directed against the encephalitogenic MBP peptide acetyl (Ac) 1-9,
      which contains a V lambda x light chain. Considering the rarity of V lambda x
      usage, we determined whether other Abs having V lambda x light chains shared
      similar antigen (Ag) specificity. We screened a panel of V lambda x-containing
      monoclonal and polyclonal Abs, of unknown specificity for reactivity with MBP.
      All such Ab, but not heavy chain isotype matched controls, bound MBP but were not
      polyreactive with other potential self Ags. The binding of a recombinant form of
      V lambda x alone to MBP demonstrated the important contribution of the V lambda x
      light chain to the reaction. With the exception of mAb F28C4 which recognizes MBP
      Ac1-9, the epitope specificity of all other V lambda x-bearing Abs was localized
      to MBP residues 25-34. These results demonstrate a unique association between V
      lambda x expression and MBP reactivity. Given that V lambda x shares sequence
      homology with T cell receptors (TCR) from encephalitogenic T lymphocytes, these
      results imply a potential role for V lambda x in the pathogenesis of EAE.

PMID- 8567973
TI  - The effect of insulin dose on the measurement of insulin sensitivity by the
      minimal model technique. Evidence for saturable insulin transport in humans.
AB  - Administration of exogenous insulin during an intravenous glucose tolerance test
      allows the use of the minimal model technique to determine the insulin
      sensitivity index in subjects with reduced endogenous insulin responses. To study
      the effect of different insulin administration protocols, we performed three
      intravenous glucose tolerance tests in each of seven obese subjects (age, 20-41
      yr; body mass index, 30-43 kg/m2). Three different insulin administration
      protocols were used: a low-dose (0.025 U/kg) infusion given over 10 min, a low
      dose (0.025 U/kg) bolus injection, and a high-dose (0.050 U/kg) bolus injection,
      resulting in peak insulin concentrations of 1,167 +/- 156, 3,014 +/- 483, and
      6,596 +/- 547 pM, respectively. The mean insulin sensitivity index was 4.80 +/-
      0.95 x 10(-5), 3.56 +/- 0.53 x 10(-5), and 2.42 +/- 0.40 x 10(-5) min-1/pM
      respectively (chi +/- SEM; P = 0.01). The association of higher peak insulin
      concentrations with lower measured insulin sensitivity values suggested the
      presence of a saturable process. Because results were not consistent with the
      known saturation characteristics of insulin action on tissue, a second saturable
      site involving the transport of insulin from plasma to interstitium was
      introduced, leading to a calculated Km of 807 +/- 165 pM for this site, a value
      near the 1/Kd of the insulin receptor. Thus, the kinetics of insulin action in
      humans in these studies is consistent with two saturable sites, and supports the
      hypothesis for transport of insulin to the interstitial space. Saturation may
      have an impact on minimal model results when high doses of exogenous insulin are
      given as a bolus, but can be minimized by infusing insulin at a low dose.

PMID- 8567972
TI  - Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism
      for rapid neutrophil recruitment after cardiac preservation.
AB  - The period of hypoxia is an important priming event for the vascular dysfunction
      that accompanies reperfusion, with endothelial cells (ECs) and neutrophils (PMNs)
      playing a central role. We hypothesized that EC Weibel-Palade (WP) body
      exocytosis during the hypoxic/ischemic period during organ preservation permits
      brisk PMN recruitment into postischemic tissue, a process further amplified in an
      oxidant-rich milieu. Exposure of human umbilical vein ECs to a hypoxic
      environment (pO2 approximately 20 torr) stimulated release of von Willebrand
      factor (vWF), stored in EC WP bodies, as well as increased expression of the WP
      body-derived PMN adhesion molecule P-selectin at the EC surface. Increased
      binding of 111In-labeled PMNs to hypoxic EC monolayers (compared with normoxic
      controls) was blocked with a blocking antibody to P-selectin, but was not
      affected by a nonblocking control antibody. Although increased P-selectin
      expression and vWF release were also noted during reoxygenation, hypoxia alone
      (even in the presence of antioxidants) was sufficient to increase WP body
      exocytosis. To determine the relevance of these observations to hypothermic
      cardiac preservation, during which the pO2 within the cardiac vasculature
      declines to similarly low levels, experiments were performed in a rodent (rat and
      mouse) cardiac preservation/transplantation model. Immunodepletion of recipient
      PMNs or administration of a blocking anti-P-selectin antibody before
      transplantation resulted in reduced graft neutrophil infiltration and improved
      graft survival, compared with identically preserved hearts transplanted into
      control recipients. To establish the important role of endothelial P-selectin
      expression on the donor vasculature, murine cardiac transplants were performed
      using homozygous P-selectin deficient and wild-type control donor hearts flushed
      free of blood/platelets before preservation/transplantation. P-selectin-null
      hearts transplanted into wild-type recipients demonstrated a marked (13-fold)
      reduction in graft neutrophil infiltration and increased graft survival compared
      with wild-type hearts transplanted into wild-type recipients. To determine
      whether coronary endothelial WP exocytosis may occur during cardiac preservation
      in humans, the release of vWF into the coronary sinus (CS) was measured in 32
      patients during open heart surgery. CS samples obtained at the start and
      conclusion of the ischemic period demonstrated an increase in CS vWF antigen (by
      ELISA) consisting of predominantly high molecular weight multimers (by
      immunoelectrophoresis). These data suggest that EC WP exocytosis occurs during
      hypothermic cardiac preservation, priming the vasculature to recruit PMNs rapidly
      during reperfusion.

PMID- 8567974
TI  - Acute hypertension activates mitogen-activated protein kinases in arterial wall.
AB  - Mitogen-activated protein (MAP) kinases are rapidly activated in cells stimulated
      with various extracellular signals by dual phosphorylation of tyrosine and
      threonine residues. They are thought to play a pivotal role in transmitting
      transmembrane signals required for cell growth and differentiation. Herein we
      provide evidence that two distinct classes of MAP kinases, the extracellular
      signal-regulated kinases (ERK) and the c-Jun NH2-terminal kinases (JNK), are
      transiently activated in rat arteries (aorta, carotid and femoral arteries) in
      response to an acute elevation in blood pressure induced by either restraint or
      administration of hypertensive agents (i.e., phenylephrine and angiotensin II).
      Kinase activation is followed by an increase in c-fos and c-jun gene expression
      and enhanced activating protein 1 (AP-1) DNA-binding activity. Activation of ERK
      and JNK could contribute to smooth muscle cell hypertrophy/hyperplasia during
      arterial remodeling due to frequent and/or persistent elevations in blood
      pressure.

PMID- 8567975
TI  - In vivo trafficking of adoptively transferred interleukin-2 expanded tumor
      infiltrating lymphocytes and peripheral blood lymphocytes. Results of a double
      gene marking trial.
AB  - Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and IL-2 appears
      to produce dramatic regressions in patients with metastatic melanoma and renal
      cancer. However, the in vivo mechanism of TIL function is not known. We conducted
      an UCLA Human Subject Protection Committee, Recombinant DNA Advisory Committee,
      and FDA-approved clinical trial using genetically-marked TIL to test the
      hypothesis that these cells have unique, tumor-specific in vivo trafficking
      patterns. TIL and PBL (as a control effector cell population) were isolated and
      expanded in parallel in vitro in IL-2-containing medium for 4-6 wk. During the
      expansion, TIL and PBL were separately transduced with the amphotropic retroviral
      vectors LNL6 and G1Na. Transduced TIL and PBL were coinfused into patients and
      their respective numbers measured in tumor, peripheral blood, and normal tissues;
      integrated provirus could be quantitated and distinguished by DNA PCR. Nine
      patients were treated (six melanoma, three renal) and received between 4.5 x
      10(8) and 1.24 x 10(10) total cells. Both "marked" TIL and PBL could be detected
      circulating in the peripheral blood, in some patients for up to 99 d after
      infusion. Marked TIL and/or PBL could be detected in tumor biopsies in six of
      nine patients as early as day 6 and as late as day 99 after infusion. No
      convincing pattern of preferential trafficking of TIL vs. PBL to tumor was noted.
      Moreover, concurrent biopsies of muscle, fat, and skin demonstrated the presence
      of TIL/PBL in comparable or greater numbers than in tumor in five patients. The
      results of this double gene marking trial provide interesting insights into the
      life span and trafficking of adoptively transferred lymphocytes, but do not
      support the hypothesis that TIL specifically traffic to tumor deposits.

PMID- 8567976
TI  - Effects of renin gene transfer on blood pressure and renin gene expression in a
      congenic strain of Dahl salt-resistant rats.
AB  - To investigate whether a BP-regulatory locus exists in the vicinity of the renin
      locus on rat chromosome 13, we transferred this chromosome segment from the Dahl
      salt-sensitive (S) rat onto the genetic background of the Dahl salt-resistant (R)
      rat. In congenic Dahl R rats carrying the S renin gene and fed an 8% salt diet,
      systolic BP was significantly lower than in progenitor Dahl R rats: 127 +/- 1
      mmHg versus 138 +/- 4 mmHg, respectively (P < 0.05). Moreover, the decreased BP
      in the congenic Dahl R strain was associated with decreased kidney renin mRNA and
      decreased plasma renin concentration. These findings demonstrate that the Dahl S
      strain carries alleles in or near the renin locus that confer lower plasma renin
      concentration and lower BP than the corresponding alleles in the Dahl R strain,
      at least when studied on the genetic background of the Dahl R rat and in the
      environment of a high salt diet. The occurrence of coincident reductions in
      kidney renin mRNA, plasma renin concentration, and BP after interstrain transfer
      of naturally occurring renin gene variants strongly suggests that genetically
      determined variation in renin gene expression can affect BP.

PMID- 8567977
TI  - Mapping a cardiomyopathy locus to chromosome 3p22-p25.
AB  - Dilated cardiomyopathy (DCM) is a common disorder characterized by cardiac
      dilation and reduced systolic function. To identify a cardiomyopathy gene, we
      studied a family with DCM associated with sinus node dysfunction,
      supraventricular tachyarrhythmias, conduction delay, and stroke. A general
      linkage approach was used to localize the disease gene in this family. Linkage to
      D3S2303 was identified with a two-point lod score of 6.09 at a recombination
      fraction of 0.00. Haplotype analyses mapped this locus to a 30 cM region of
      chromosome 3p22-p25, excluding candidate genes encoding a G-protein (GNAI2),
      calcium channel (CACNL1A2), sodium channel (SCN5A), and inositol triphosphate
      receptor (ITPR1). These data indicate that a gene causing DCM associated with
      rhythm and conduction abnormalities is located on chromosome 3p, and represent
      the first step toward disease gene identification.

PMID- 8567978
TI  - Cardiac-specific overexpression of phospholamban alters calcium kinetics and
      resultant cardiomyocyte mechanics in transgenic mice.
AB  - Phospholamban is the regulator of the cardiac sarcoplasmic reticulum (SR) Ca(2+)
      ATPase activity and an important modulator of basal contractility in the heart.
      To determine whether all the SR Ca(2+)-ATPase enzymes are subject to regulation
      by phospholamban in vivo, transgenic mice were generated which overexpressed
      phospholamban in the heart, driven by the cardiac-specific alpha-myosin heavy
      chain promoter. Quantitative immunoblotting revealed a twofold increase in the
      phospholamban protein levels in transgenic hearts compared to wild type
      littermate hearts. The transgenic mice showed no phenotypic alterations and no
      changes in heart/body weight, heart/lung weight, and cardiomyocyte size. Isolated
      unloaded cardiac myocytes from transgenic mice exhibited diminished shortening
      fraction (63%) and decreased rates of shortening (64%) and relengthening (55%)
      compared to wild type (100%) cardiomyocytes. The decreases in contractile
      parameters of transgenic cardiomyocytes reflected decreases in the amplitude
      (83%) of the Ca2+ signal and prolongation (131%) in the time for decay of the
      Ca2+ signal, which was associated with a decrease in the apparent affinity of the
      SR Ca(2+)-ATPase for Ca2+ (56%), compared to wild type (100%) cardiomyocytes. In
      vivo analysis of left ventricular systolic function using M mode and pulsed-wave
      Doppler echocardiography revealed decreases in fractional shortening (79%) and
      the normalized mean velocity of circumferential shortening (67%) in transgenic
      mice compared to wild type (100%) mice. The differences in contractile parameters
      and Ca2+ kinetics in transgenic cardiomyocytes and the depressed left ventricular
      systolic function in transgenic mice were abolished upon isoproterenol
      stimulation. These findings indicate that a fraction of the Ca(2+)-ATPases in
      native SR is not under regulation by phospholamban. Expression of additional
      phospholamban molecules results in: (a) inhibition of SR Ca2+ transport; (b)
      decreases in systolic Ca2+ levels and contractile parameters in ventricular
      myocytes; and (c) depression of basal left ventricular systolic function in vivo.

PMID- 8567979
TI  - Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in
      vitro and models the placental defects that occur in preeclampsia.
AB  - During normal human pregnancy a subpopulation of fetal cytotrophoblast stem cells
      differentiate and invade the uterus and its arterioles. In the pregnancy disease
      preeclampsia, cytotrophoblast differentiation is abnormal and invasion is
      shallow. Thus, the placenta is relatively hypoxic. We investigated whether
      lowering oxygen tension affects cytotrophoblast differentiation and invasion.
      Previously we showed that when early gestation cytotrophoblast stem cells are
      cultured under standard conditions (20% O2) they differentiate/invade,
      replicating many aspects of the in vivo process. Specifically, the cells
      proliferate at a low rate and rapidly invade extracellular matrix (ECM)
      substrates, a phenomenon that requires switching their repertoire of integrin
      cell-ECM receptors, which are stage-specific antigens that mark specific
      transitions in the differentiation process. In this study we found that lowering
      oxygen tension to 2% did not change many of the cells' basic processes. However,
      there was a marked increase in their incorporation of [3H]thymidine and 5-bromo
      2'-deoxyuridine (BrdU). Moreover, they failed to invade ECM substrates, due at
      least in part to their inability to completely switch their integrin repertoire.
      These changes mimic many of the alterations in cytotrophoblast
      differentiation/invasion that occur in preeclampsia, suggesting that oxygen
      tension plays an important role in regulating these processes in vivo.

PMID- 8567980
TI  - Imogen 38: a novel 38-kD islet mitochondrial autoantigen recognized by T cells
      from a newly diagnosed type 1 diabetic patient.
AB  - Cell-mediated autoimmune attack directed against islet proteins of approximately
      38 kD in size has been associated with type 1 diabetes. A novel murine cDNA
      encoding an antigen of this size was cloned using a screening procedure based on
      the proliferative response of a human diabetic T cell clone (1C6) to a
      recombinant antigen epitope library. Membrane preparations from COS 7 cells
      transfected with the full-length 1,267-bp cDNA elicited a proliferative response
      from the reporter T cells comparable to that of the defined peptide epitope and
      native insulinoma antigen. In vitro translation and transfection experiments
      suggested that the protein is initially synthesized as a 44-kD protein and then
      processed to the native 38-kD form through the proteolytic removal of a 54-aa NH2
      terminal mitochondrial targeting sequence. Differential centrifugation, Percoll
      density gradient centrifugation, and immunofluorescence studies confirmed
      localization of the antigen to mitochondria. Northern blot, Western blot, and 1C6
      T cell proliferation assays showed that, although imogen 38 was more highly
      expressed in beta cell than alpha cell lines, it was also present in other
      tissues. It is concluded that imogen 38 may be a target for bystander autoimmune
      attack in diabetes rather than a primary autoantigen.

PMID- 8567981
TI  - Evidence for an essential role of reactive oxygen species in the genesis of late
      preconditioning against myocardial stunning in conscious pigs.
AB  - Conscious pigs underwent a sequence of 10 2-min coronary occlusions, each
      separated by 2 min of reperfusion, for three consecutive days (days 1, 2, and 3).
      On day 1, pigs received an i.v. infusion of a combination of antioxidants
      (superoxide dismutase, catalase, and N-2 mercaptopropionyl glycine; group II, n =
      9), nisoldipine (group III, n = 6), or vehicle (group I [controls], n = 9). In
      the control group, systolic wall thickening (WTh) in the ischemic-reperfused
      region on day 1 remained significantly depressed for 4 h after the 10th
      reperfusion, indicating myocardial "stunning." On days 2 and 3, however, the
      recovery of WTh improved markedly, so that the total deficit of WTh decreased by
      53% on day 2 and 56% on day 3 compared with day 1 (P < 0.01), indicating the
      development of a powerful cardioprotective response (late preconditioning against
      stunning). In the anti-oxidant-treated group, the total deficit of WTh on day 1
      was 54% less than in the control group (P < 0.01). On day 2, the total deficit of
      WTh was 85% greater than that observed on day 1 and similar to that observed on
      day 1 in the control group. On day 3, the total deficit of WTh was 58% less than
      that noted on day 2 (P < 0.01). In the nisoldipine-treated group, the total
      deficit of WTh on day 1 was 53% less than that noted in controls (P < 0.01). On
      days 2 and 3, the total deficit of WTh was similar to the corresponding values in
      the control group. These results demonstrate that: (a) in the conscious pig,
      antioxidant therapy completely blocks the development of late preconditioning
      against stunning, indicating that the production of reactive oxygen species (ROS)
      on day 1 is the mechanism whereby ischemia induces the protective response
      observed on day 2; (b) antioxidant therapy markedly attenuates myocardial
      stunning on day 1, indicating that ROS play an important pathogenetic role in
      postischemic dysfunction in the porcine heart despite the lack of xanthine
      oxidase; (c) although the administration of a calcium-channel antagonist
      (nisoldipine) is as effective as antioxidant therapy in attenuating myocardial
      stunning on day 1, it has no effect on late preconditioning on day 2, indicating
      that the ability of antioxidants to block late preconditioning is not a
      nonspecific result of the mitigation of postischemic dysfunction on day 1.
      Generation of ROS during reperfusion is generally viewed as a deleterious
      process. Our finding that ROS contribute to the genesis of myocardial stunning
      but, at the same time, trigger the development of late preconditioning against
      stunning supports a complex pathophysiological paradigm, in which ROS play an
      immediate injurious role (as mediators of stunning) followed by a useful function
      (as mediators of subsequent preconditioning).

PMID- 8567983
TI  - Binding kinetics of monoclonal antibody using antigen-beta-galactosidase hybrid
      protein: application to measurement of peptide antigenicity.
AB  - A simple method for determination of binding kinetics of a solid-phase antibody
      using antigen-beta-galactosidase hybrid protein was evaluated. To minimize
      conformational change of the antigen binding site of the antibody when directly
      binding to a microtiter plate, the microtiter plate was precoated with protein A.
      The binding and free antigen concentrations were directly obtained from the beta
      galactosidase activity. This method can be used for analyses of the equilibrium
      dissociation constant (KD), and the association (Kass) and dissociation (Kdiss)
      rate constants. Peptide antigenicity was also analyzed by competitive ELISA using
      this method. Since both antigen-beta-galactosidase and the peptide used are
      localized in the fluid-phase, the proper affinity constant (KA) of the peptide
      can be estimated from the KD value of the antigen-beta-galactosidase-antibody
      interaction, and from the IC50 value of the peptide.

PMID- 8567982
TI  - Purification and characterization of a naturally processed hepatitis B virus
      peptide recognized by CD8+ cytotoxic T lymphocytes.
AB  - In vitro studies in patients with hepatitis B virus (HBV) infection have
      suggested that hepatocytolysis induced by CD8+ cytotoxic T lymphocytes (CTLs) is
      the most important effector pathway in eliminating infected cells. The
      recognition is implicated in the endogenously processed HBV antigens in the
      context of HLA class I molecules presented on the liver cell membrane. However,
      the naturally occurring HBV peptide antigens have not yet been demonstrated. We
      report here that a naturally processed peptide antigen P2 was isolated from HLA
      class I molecules of HBV-infected liver cell membrane. The P2 peptide exhibited
      the activity of sensitizing target cells for lysis by CD8+ CTLs. The P2 sequence
      (YVNVNMGLK) purified from liver tissue was in concordance with that encoded by
      the viral genome for the HBV nucleocapsid antigen or HBcAg 88-96. P2 peptide
      could also be isolated from the EBV-transformed B cells that were transfected by
      HBcAg-expressing vector. The P2 epitope, sharing the HLA-A11 binding motifs, was
      recognized by HLA-A11-restricted CD8+ CTLs. The data provided direct evidence
      that, in hepatitis B patients, antigenic peptides of HBV were processed by
      hepatocytes, presented with the class I MHC molecules, and recognized by CD8+
      CTLs.

PMID- 8567984
TI  - Enzyme-linked immunosorbent assay (ELISA) for rainbow trout (Oncorhynchus mykiss)
      vitellogenin.
AB  - 1. A specific and simple enzyme-linked immunoassay for rainbow trout
      (Onchorynchus mykiss) vitellogenin (Vtg) is described. This assay is performed
      using a rabbit antiserum for Vtg purified from trout plasma. 2. This assay is
      based upon the competition between soluble Vtg and Vtg adsorbed on microtiter
      plates, for the rabbit anti-Vtg antibody binding sites. 3. The adsorbed Vtg
      antibody complexes are revealed through the peroxidase-antiperoxidase antibody,
      which is colored by o-phenylendiamin. This assay can be performed in a day and a
      night. 4. Under our conditions, 90-20% of binding gave a sensibility range of 33
      1473 ng/ml. With almost a 50% binding yield (335 ng/ml) the intra-assay
      coefficient of variation (CV) was 5.2% (n = 26) and the inter-assay CV was 12.5%
      (n = 5). 5. There was low immunological cross-reactivity with sera from other
      salmonids and with ovary extracts. Extracts of liver from oestrogenized male
      rainbow trout yielded displacements parallel to the vitellogenin standard and to
      mature female serum or oestrogenized male serum. 6. This enzyme immunoassay is
      simple and easy to use. Its great specificity allows its use only for the rainbow
      trout species.

PMID- 8567985
TI  - Transforming growth factor-alpha in human submandibular gland and saliva.
AB  - A sensitive sandwich enzyme immunoassay (EIA) for transforming growth factor
      alpha (TGF-alpha) utilizing a polyclonal antibody that recognizes limited
      epitopes of both human TGF-alpha and rat TGF-alpha in combination with a
      monoclonal anti-TGF-alpha IgG1 galactosidase conjugate was developed. This assay
      shows no cross-reactivity with human epidermal growth factor. We can quantify the
      TGF-alpha level in not only human TGF-alpha (detection limit: 1 pg/ml), but also
      rat TGF-alpha (detection limit: 10 pg/ml) by virtue of cross-reactivity.
      Employing this assay system, we demonstrated that TGF-alpha is present in both
      human submandibular glands and submandibular/sublingual saliva.

PMID- 8567986
TI  - Optimization of the covalent conjugating procedure (NaIO4) of horseradish
      peroxidase to antibodies for use in enzyme-linked immunosorbent assay.
AB  - The procedure for covalent conjugation of horseradish peroxidase (POD) to goat
      anti-human IgG (GAHG) molecules was systematically optimized in terms of reactant
      molar ratio, time of reaction, pH, and temperature. The optimum conjugation
      procedure was defined by the conditions that produced an enzyme-labeled Ab with
      the highest specific activity in immunosorbent assays for normal human IgG
      (NHIgG). The best conditions are: Sodium meta-periodate (NaIO4) to Ab molar ratio
      during oxidation is 40:1; time of oxidation is 5 min at 37 degrees C; oxidation
      reaction is conducted at pH 5.0; the molar ratio of POD:GAHG is 6:1; the
      conjugation time is 24 h at 4 degrees C; and the optimal conjugation pH is 10.0.
      A conjugate constructed under these conditions is capable of generating 1.8 and
      12.6 times more specific signals (delta A650nm/min) than the best and worst
      commercial conjugates, respectively. This conjugate is also able to detect NHIgG
      at a concentration of 2.25 x 10(-13) M, a sensitivity 25 times that achieved by
      most comparable commercial products in identical assays.

PMID- 8567987
TI  - Serologic diagnosis of caprine arthritis-encephalitis by ELISA with two
      recombinant proteins in a parallel testing format.
AB  - A scheme for screening sera for antibodies to caprine arthritis-encephalitis
      virus (CAEV) was evaluated for its ability to identify positive and negative
      samples in a population with heterogeneous risk factors, using the criteria of
      sensitivity, specificity and positive predictive value. Five hundred caprine
      serum samples were tested using a transmembrane recombinant-based ELISA. Those
      that gave positive results were considered positive, while those with equivocal
      or negative results were retested with a core recombinant protein-based ELISA.
      Equivocal results after the second test were considered indeterminate and
      retesting is advised. Using this approach, a sensitivity, specificity and
      positive predictive value of 98.8%, 97.2% and 98.6% were obtained. These values
      are superior to those obtained by these tests used individually. The high
      sensitivity, specificity and predictive value of this new scheme of CAEV
      screening make it an attractive addition to any control or eradication program.

PMID- 8567988
TI  - Induction and characterization of monoclonal anti-idiotypic antibodies to tick
      borne encephalitis virus neutralizing antibody.
AB  - Seven monoclonal anti-idiotypic antibodies (anti-ID MAbs, Ab2) were generated
      against virus-neutralizing and hemagglutination-inhibiting monoclonal antibody
      (Ab1) specific for tick-borne encephalitis (TBE) virus. Six of these anti-ID MAbs
      inhibited the binding of Ab1 to the virus antigen, thus classifying these anti-ID
      antibodies as Ab2 beta or AB2 gamma. Inhibition tests with heterologous anti-TBE
      sera revealed that these anti-ID MAbs were not recognized by anti-TBE antibodies
      and therefore they do not carry an internal image of TBE virus antigen. Hence,
      the anti-ID MAbs may be classified as Ab2 gamma type. None of the anti-ID MAbs
      induced production of antiviral antibodies nor protective immunity in syngeneic
      Balb/c mice. Using these anti-ID MAbs four nonoverlapping idiotopes were
      identified on Ab1 variable region.

PMID- 8567989
TI  - Editors on editors.

PMID- 8567990
TI  - Subarachnoid haemorrhage and myths about saccular aneurysms.

PMID- 8567991
TI  - Review of a consultant microbiologist's work practice--an audit.

PMID- 8567992
TI  - Epidermal differentiation and dermal changes in healing following treatment of
      surgical wounds with sheets of cultured allogeneic keratinocytes.
AB  - AIMS: To establish the structural changes that occur in deep surgical wounds
      engrafted with allogeneic sheets, their time course and inter-relation. METHODS:
      Deep surgical wounds following shave excision of tattoos (down to deep
      dermis/subcutaneous fat) were treated with sheets of sex mismatched allogeneic
      keratinocytes in 19 patients and then biopsied weekly until wound healing was
      complete. More superficial surgical wounds--that is, 20 standard skin graft donor
      sites, were biopsied at seven to 10 days (all healed) following application of
      keratinocyte allografts. All biopsy specimens were examined with a large panel of
      monoclonal antibodies to keratins, envelope proteins, basement membrane
      components, and to extracellular matrix components. RESULTS: The
      hyperproliferative keratin pair K6/16 was expressed in all wounds, for up to six
      weeks in keratinocyte grafted deep wounds, and up to six months in split
      thickness skin grafted wounds. CONCLUSIONS: Keratins 6 and 16 have not been
      detected in normal skin, although the relevant mRNA has. This raises the
      possibility of regulation at a post-transcriptional level allowing a rapid
      response to injury with cytoskeletal changes that may aid cell migration. This
      keratin pair offers the most sensitive marker for altered epidermis following
      wounding.

PMID- 8567993
TI  - Role of transforming growth factor beta 1 on hepatic regeneration and apoptosis
      in liver diseases.
AB  - AIMS: To investigate the effects of transforming growth factor beta 1 (TGF-beta
      1) on regeneration and induction of apoptosis of liver cell and bile duct in
      various liver diseases. METHODS: Formalin fixed paraffin wax sections of 18 liver
      tissue samples were obtained by needle biopsy, surgery, or necropsy; these
      included six liver cirrhosis, three obstructive jaundice; five fulminant
      hepatitis, one subacute hepatitis, and three normal liver. Expression of TGF-beta
      1, apoptosis related Le(y) antigen, Fas antigen, a receptor for tumour necrosis
      factor, and biotin nick end labelling with terminal deoxynucleotidyl transferase
      mediated dUTP (TUNEL) for locating DNA fragmentation, was investigated
      histochemically. RESULTS: TGF-beta 1 was expressed in areas of atypical bile duct
      proliferation, where bile duct continuously proliferated from liver cells. In
      occlusive jaundice and fulminant hepatitis, TUNEL was positive in nuclei and
      cytoplasm of metaplastic cells which formed incomplete bile ducts, and these
      cells appeared to extend from TGF-beta 1 expressing liver cells. Fas antigen was
      found only on the cell membrane of proliferated bile duct in fulminant hepatitis,
      which differed from TGF-beta 1 and TUNEL positive areas. Le(y) antigen was
      expressed in liver cell and bile duct at the areas with atypical bile duct
      proliferation, but its coexpression with TUNEL was rare. CONCLUSIONS: TGF-beta 1
      plays a role in the arrest of liver cell regeneration and atypical bile duct
      proliferation, and in areas of rapidly progressing atypical bile duct
      proliferation, such as in fulminant hepatitis or bile retention. Apoptosis
      appears to be induced by TGF-beta 1. This phenomenon may account for the
      inadequate hepatic regeneration that occurs with liver disease.

PMID- 8567994
TI  - Relation between stage, grade, proliferation, and expression of p53 and CD44 in
      adenomas and carcinomas of the colorectum.
AB  - AIMS: To investigate the changes in and relations among p53, CD44 and MIB-1
      expression in adenocarcinomas of the colorectum and to determine whether these
      changes are progressive across the adenoma-carcinoma sequence. METHODS:
      Expression of p53 protein, CD44 adhesion molecule and MIB-1 proliferation antigen
      was detected using immunohistochemistry in 68 colorectal carcinomas and 32
      colorectal adenoma. The staining characteristics were compared with degree of
      dysplasia in adenomas, and differentiation and Dukes' stage in carcinomas.
      Results were analysed and assessed using Spearman's rank correlation and
      independent t tests. RESULTS: p53 staining was present in som adenomas and
      correlated with the degree of dysplasia. There was significantly more staining in
      carcinomas than adenomas and significant correlation between staining and Dukes'
      stage. CD44 staining was maximal in adenomas, diminished in carcinomas and was
      minimal in metastasising carcinomas. There was inverse correlation between p53
      and CD44 expression across the adenoma-carcinoma-metastasising carcinoma
      sequence. MIB-1 expression was highest in carcinomas but did not correlate with
      either p53 or CD44 expression. CONCLUSIONS: There are progressive changes in p53,
      CD44 and MIB-1 expression in adenomas and carcinomas. A combination of these
      tests may prove useful in assessing which patients with adenomas are at greatest
      risk of progressing to carcinoma.

PMID- 8567995
TI  - Orthostatic hypotension and vasodilatory peptides in bronchial carcinoma.
AB  - AIM: To determine whether inappropriately secreted vasodilatory peptides have a
      role in the pathogenesis of orthostatic (postural) hypotension, a recognised
      paraneoplastic effect of bronchial malignancies usually attributed to immune
      mediated destruction of autonomic ganglia. METHODS: Serum concentrations of three
      vasodilatory peptides, atrial natriuretic peptide (ANP), vasoactive intestinal
      polypeptide (VIP) and calcitonin gene related peptide (CGRP), were measured in
      111 patients with bronchial carcinoma and 35 controls prospectively screened for
      orthostatic hypotension (> 20 mmHg drop in systolic blood pressure on repeated
      occasions on standing from the supine position) and in whom other causes of this
      condition were excluded. RESULTS: Twenty two (20%) patients with carcinoma and
      two (6%) controls had orthostatic hypotension according to the criteria used.
      Serum concentrations of ANP, VIP and CGRP were elevated above normal in,
      respectively, 25 (23%), 10 (9%) and eight (7%) patients with carcinoma and in six
      (18%), zero and three (9%) controls. There was no correlation between orthostatic
      hypotension and concentrations of any of the vasodilatory peptides. CONCLUSION:
      Elevated serum concentrations of ANP and CGRP were no more frequent in subjects
      with bronchial carcinoma than in controls and could not be attributed to the
      tumour, although there was a possible association for VIP. Orthostatic
      hypotension was more common in patients with carcinoma, but there was no evidence
      that the peptides measured played a role in its pathogenesis.

PMID- 8567996
TI  - HPV type 16 in conjunctival and junctional papilloma, dysplasia, and squamous
      cell carcinoma.
AB  - AIMS: To clarify the role of human papillomavirus (HPV) infection in the
      development of papilloma, dysplasia, squamous cell carcinoma, and basal cell
      epithelioma arising from the eyelids, including the tunica conjunctiva palpebrum
      (conjunctiva), its junction to epidemis of eyelid skin (junction), and eyelid
      skin. METHODS: Sixteen cases of papilloma, four of dysplasia, four of squamous
      cell carcinoma, and 12 of basal cell epithelioma were examined using formalin
      fixed and paraffin embedded samples. Detection of HPV-DNA was performed by PCR
      RFLP and in situ hybridisation (ISH) methods. RESULTS: HPV-16 was detected in
      12/16 papillomas (75%), 2/4 dysplasias (50%), and 1/4 squamous cell carcinomas
      (25%) but in none of the basal cell epitheliomas. No other HPV subtypes were
      found. ISH assay showed positive signals in only two cases of dysplasia and
      squamous cell carcinoma. The mean age of HPV-16 positive dysplasia and squamous
      cell carcinoma cases (81.7 years) was significantly higher than that of HPV-16
      positive papilloma cases (p < 0.01). CONCLUSIONS: Based on the presence of HPV-16
      in both benign and malignant lesions and the age distribution, it seems likely
      that HPV-16 alone may be incapable of causing development of conjunctival and
      junctional dysplasia and squamous cell carcinoma, and that any correlation
      between the papilloma-squamous cell carcinoma sequence and HPV infection may be
      due to rare events.

PMID- 8567997
TI  - Ten year follow up study of lymphocytic gastritis: further evidence on
      Helicobacter pylori as a cause of lymphocytic gastritis and corpus gastritis.
AB  - AIMS: To examine the course of lymphocytic gastritis and its relation to
      Helicobacter pylori (H pylori) infection in a 10 year follow up. METHODS: Ninety
      six patients were originally examined for dyspepsia in 1981. Gastroscopies with
      stepwise biopsies were performed on all the patients initially and after an
      interval of 10 years. RESULTS: Nine per cent of the patients (9/96) had features
      of lymphocytic gastritis in gastric biopsy at the first examination, and 12.5%
      (12/96) at the second examination; 7/9 patients (78%) had persistent lymphocytic
      gastritis during the follow up; in two the diagnostic features of lymphocytic
      gastritis had disappeared, and five had a new diagnosis of lymphocytic gastritis
      at the second examination. At the second examination 9/12 lymphocytic gastritis
      patients (75%) were H pylori positive histologically, while all had specific
      antibodies to H pylori. The lymphocytic gastritis patients had higher grades of
      gastritis (p = 0.009), neutrophilic and eosinophilic granulocytes, mononuclear
      inflammatory cells, and foveolar hyperplasia in the corpus mucosa, but smaller
      numbers of H pylori, than the H pylori positive patients without lymphocytic
      gastritis. The appearance of lymphocytic gastritis during the 10 year interval
      was associated with increases in the grades of corpus gastritis and neutrophilic
      granulocytes (p = 0.043 for both). During the follow up, the patients with
      lymphocytic gastritis, but not the H pylori positive patients without lymphocytic
      gastritis, appeared to have a significant increase in the grade of intestinal
      metaplasia in the corpus mucosa (p = 0.043). CONCLUSIONS: In some patients H
      pylori may cause a gastritis that predominates in the corpus and is associated
      with an increase in the intraepithelial lymphocyte count. This form of gastritis
      may cause progression of intestinal metaplasia.

PMID- 8567998
TI  - Spectrotypic analysis of antibodies to Helicobacter pylori in patients with
      antral gastritis and duodenal ulcer.
AB  - AIMS: To investigate the anti Helicobacter pylori (H pylori) spectrotype
      associated with (a) antral gastritis and duodenal ulcer; (b) the H pylori
      eradicating treatment. METHODS: Spectrotypic analysis was performed by
      isoelectric focusing and reverse blotting (IEFRB) in a cross sectional study on
      sera from 70 patients with antral gastritis and duodenal ulcer. In addition, a
      longitudinal study was performed on 40 of these patients (20 with antral
      gastritis and 20 with duodenal ulcer) who underwent eradicating treatment.
      RESULTS: The cross sectional study showed that the oligoclonal spectrotype was
      present in 74% of antral gastritis patients and in 85% of duodenal ulcer
      patients. In only a minority of subjects (23% with antral gastritis and 3% with
      duodenal ulcer) was a polyclonal spectrotype observed. The longitudinal study
      showed a reduction in the intensity of the spectrotypic bands in 5/10 antral
      gastritis patients with eradicated H pylori as opposed to only 2/10 patients
      without eradication. A reduction was also observed in 6/11 eradicated v 0/9 non
      eradicated patients with duodenal ulcer. Collectively, a reduction in the
      spectrotype was observed in 11/21 patients (52%) who--independently of the
      disease--underwent H pylori eradication, as opposed to 2/19 of the non-responder
      patients (10.5%). The polyclonal spectrotype was found exclusively in four
      patients with antral gastritis, all belonging to the group without eradication of
      H pylori after eradicating treatment. CONCLUSIONS: The anti H pylori oligoclonal
      spectrotype is the most common pattern observed in patients with antral gastritis
      and duodenal ulcer. After H pylori eradicating treatment the spectrotype does not
      change qualitatively, but the polyclonal pattern seems to be predictive of a poor
      response to eradication.

PMID- 8567999
TI  - Quality assessment of Microbe Base antimicrobial susceptibility data.
AB  - AIMS: To assess the quality of centres contributing antimicrobial susceptibility
      data to a centralised database. METHODS: Twelve organisms were distributed to 31
      regional microbiology laboratories contributing data to a centralised
      susceptibility database. Participants were asked to determine susceptibilities to
      certain antibiotics by their routine method and return the data to the Department
      of Microbiology, Royal Hallamshire Hospital, Sheffield, for analysis. RESULTS:
      Results for the overwhelming majority of organism/antibiotic combinations were in
      agreement with expected results. Reasons for discrepancies included the non
      bimodal distribution of susceptibilities, the use of different content discs,
      and, more importantly, minimum inhibitory concentrations falling close to
      breakpoint values. CONCLUSIONS: It is inevitable that any large multicentre
      database will contain a degree of inaccurate data. This study has highlighted
      several areas where discrepant results have occurred and has enabled Glaxo
      Laboratories to approach individual laboratories to address this problem. This
      study emphasises the value and consistency of Microbe Base as the largest
      database, of its kind, nationally.

PMID- 8568000
TI  - Audit of an emergency biochemistry service.
AB  - AIM: To examine a model for the evaluation of appropriateness of testing in an
      emergency biochemistry laboratory. METHODS: A model was devised in which incoming
      emergency test requests were categorised as appropriate or inappropriate.
      Explicit criteria were used to define eight minor categories, which were chosen
      to reflect accurately current working practice within the hospital and
      laboratory. Five junior medical staff each undertook a prospective 24 hour
      assessment, during which time all incoming requests were monitored and
      categorised according to these criteria. Concordance between monitors was
      evaluated before and during assessments. RESULTS: Of 509 requests, 384 (75%) were
      appropriate and 125 (25%) were inappropriate according to the criteria used to
      define categories. Inappropriate requests fell into three main groups:
      preoperative samples (43.2% (54/125) of all inappropriate requests), missed
      routine samples (33.6% (42/125)) and accelerated (priority) analyses (16%
      (20/125)). Various other reasons accounted for the remaining 7.2% (9/125).
      CONCLUSION: This model may be used to obtain valid information about current
      clinical and laboratory practice. Strategies to reduce the number of
      inappropriate requests have been identified in order to reserve the emergency
      service for situations of true need.

PMID- 8568001
TI  - Immunoblotting in the diagnosis of culture negative endocarditis caused by
      streptococci and enterococci.
AB  - AIM: To improve the diagnosis of culture negative endocarditis by diagnosing
      cases due to streptococci and enterococci. METHODS: Serum samples were
      immunoblotted against extracts of the commonest streptococci and enterococci.
      They were selected from patients with a cardiac murmur, persistent pyrexia and at
      least three negative blood cultures. The presence of patterns of endocarditis
      species specific antigenic bands was measured and correlated with clinical
      outcome. RESULTS: Negative serology was found in 28 patients where the diagnosis
      of endocarditis was rejected or, if proved, staphylococcal, yeast, Gram negative,
      systemic lupus erythematosus, due to Q fever or Chlamydia psittaci or
      nonbacterial thrombotic. Positive serology was found in 27 of the 34 patients
      where the response to antibiotics suggested streptococcal or enterococcal
      infection. In 22 of these there was objective evidence of endocarditis. Positive
      serology was also found in three of four further patients with vegetations at
      necropsy. CONCLUSION: The identification of patterns of antibody response on
      immunoblotting can be used to make a specific diagnosis of streptococcal or
      enterococcal endocarditis in the absence of positive blood cultures.

PMID- 8568002
TI  - Lymphocyte subset counts in skin puncture and venous blood compared.
AB  - To determine whether skin puncture blood can be used reliably for CD4 lymphocyte
      counts, the numbers of the major subsets of lymphocytes were assessed in paired
      venous and skin puncture blood samples from 22 children and 10 adults. Paired
      values were highly correlated, with skin puncture values being about 7% higher
      than venous values for each cell type. Differences were of borderline statistical
      significance for total lymphocytes and for each subset except CD3+ CD8+ T
      lymphocytes. Nevertheless, the magnitude of the differences was small and
      unlikely to be of clinical importance, and it seems that skin puncture samples
      may be preferable for CD4 counts in children or adults with difficult venous
      access.

PMID- 8568003
TI  - Detection of Ki67 antigen by a new sheep polyclonal antiserum.
AB  - This report describes the characterisation of a polyclonal sheep antiserum
      against the Ki67 antigen. On western blots, this antiserum recognises a pair of
      bands of high molecular weight identical with those seen with another polyclonal
      Ki67 antiserum and the MIB 1 monoclonal antibody. The new antiserum showed
      nuclear staining of a proportion of cells in paraffin wax embedded tissue
      sections following antigen retrieval using a microwave oven or pressure cooker.
      This staining pattern was blocked by incubating the serum with the peptide used
      as immunogen. The proportion and distribution of immunostained nuclei was
      identical with that seen with the alternative reagents that recognise the Ki67
      antigen. The new reagent stained the same proportion of cells when used over a
      wide range of dilutions. There was no cross-reactivity with unrelated antigens
      sometimes detected by the monoclonal antibodies.

PMID- 8568004
TI  - Non-neoplastic glandular structures in bone marrow: a technical artefact.
AB  - A case of non-neoplastic glandular structures embedded in the centre of a bone
      marrow trephine biopsy is described. This is a hitherto unreported phenomenon.
      These glandular structures originated from the dermal sweat gland and represented
      an artefactual lesion produced by the biopsy procedure. The importance of
      considering the possibility of non-neoplastic glandular structures in bone marrow
      is stressed, in order to avoid a misdiagnosis of metastatic adenocarcinoma.

PMID- 8568005
TI  - Clear cell adenocarcinoma of the colon.
AB  - A case of clear cell adenocarcinoma of the colon is reported. The histological
      examination of both the surgical specimen and of the metastases at necropsy
      showed columnar or polygonal cells with vesicular nuclei. The cytoplasm was
      usually clear with multiple, often empty looking vacuoles. From a panel of
      histochemical and immunohistochemical reactions, carcinoembryonic antigen and
      tissue polypeptide antigen showed strong positivity. The histochemical and
      immunohistochemical differential diagnosis with another common clear cell tumour,
      namely clear cell renal adenocarcinoma, is discussed.

PMID- 8568006
TI  - Introduction of computer assisted control of oral anticoagulation in general
      practice.
AB  - The number of patients referred to hospital clinics for monitoring of oral
      anticoagulation continues to rise rapidly. Introduction of computer programs for
      the control of oral anticoagulation improves the quality of anticoagulant control
      in hospital clinics. This approach has now been extended to include patients
      managed in general practice. Results confirm that the quality of anticoagulation
      can also be improved in these patients. A standard approach to anticoagulation
      for hospital and community based patients has also facilitated the transfer of
      patients on warfarin from the hospital anticoagulant clinics to the community
      with no deterioration in the quality of anticoagulant control. As a result, the
      workload in the hospital anticoagulant clinic has fallen for the first time.

PMID- 8568007
TI  - Pharmacokinetics of carboplatin in a patient with cervical cancer with ureteric
      obstruction before, during, and after hemodialysis.
AB  - The pharmacokinetics of total and free (ultrafilterable) platinum were
      investigated in a patient with cervical cancer with ureteric obstruction who, at
      the time of carboplatin administration, appeared to have a mild renal impairment
      (i.e., creatinine clearance 1 mL/s), but developed an acute renal failure shortly
      thereafter, which required hemodialysis. The decline in the concentration of
      total or free Pt in plasma as function of time correlated well (P < 0.0098) with
      that of serum creatinine concentration. The elimination half-lives (t1/2) of
      total and free Pt in this patient were eight- and nine-fold longer than those
      observed earlier for patients with normal renal function, and the total body
      clearance was 12.4% and 18.4%, respectively. Although t1/2 of Pt during dialysis
      was two to three times (total Pt) and eight times (free Pt) shorter than those
      observed before and after dialysis, three sessions of hemodialysis removed only
      5.6% of total Pt and 9.3% of free Pt. Because the pre- and post-dialysis t1/2
      values were similar, hemodialysis apparently had no impact on the intrinsic
      elimination of Pt in this patient.

PMID- 8568008
TI  - Losartan does not affect the pharmacokinetics and pharmacodynamics of warfarin.
AB  - Losartan, on orally active, nonpeptide angiotensin II receptor antagonist is
      being developed as a therapeutic agent for the treatment of hypertension and
      heart failure. Many patients requiring anticoagulant therapy with warfarin also
      may have hypertension or heart failure, and thus, are potential candidates for
      losartan therapy. This study was designed to investigate whether losartan at
      likely dosage levels would alter the anticoagulant response to warfarin. In a two
      period, placebo-controlled, randomized, crossover study, ten healthy male
      subjects received a single oral dose of 30 mg warfarin sodium on the seventh day
      of a 13-day treatment with losartan, 100 mg daily by mouth, or placebo. Multiple
      plasma samples were collected over a 6-day period after both warfarin doses for
      the measurements of R- and S-warfarin concentrations and prothrombin times. The
      pharmacokinetics of R- and S-warfarin were comparable in the absence and presence
      of losartan (no significant effects of losartan on area under the curve, Cmax, or
      tmax). Losartan also had no significant effect on the anticoagulant effect of
      warfarin, as assessed by the area under the prothrombin time versus time curve
      and the maximum response for prothrombin time. The lack of pharmacokinetic or
      pharmacodynamic interaction between warfarin and losartan observed in this
      investigation suggests that a clinically important interaction between these
      drugs is unlikely to occur in patients requiring concomitant administration of
      both drugs.

PMID- 8568009
TI  - Pharmacokinetics of moricizine in young patients.
AB  - Moricizine is a novel phenothiazine antiarrhythmic agent that depresses the
      activity of ectopic foci, has a low incidence of adverse effects relative to
      other agents, and is useful in treating pediatric atrial ectopic tachycardia. A
      study was conducted to determine the pharmacokinetics of moricizine in children
      after oral administration. Moricizine was isolated from frozen serum obtained
      from four male patients (ages 7, 8, 9, and 18 years) receiving the drug for
      supraventricular tachycardia and analyzed by high-performance liquid
      chromatography with ultraviolet detection according to an established protocol.
      Peak serum levels were between 400 and 2000 ng/mL. Elimination of moricizine did
      not follow simple single-compartment pharmacokinetics. In three patients we
      observed an increase or slower decline in blood level occurring after 4 hours.
      Because of the paroxysmal nature of the tachycardias, decreases in patient heart
      rate could not be correlated with moricizine blood level. These results suggest
      that the pediatric pharmacokinetics of moricizine excretion are complex and may
      differ from those seen in adults.

PMID- 8568011
TI  - Can chronic maternal drug therapy alter the nursing infant's hepatic drug
      metabolizing enzyme pattern?
AB  - This study was carried out to investigate whether minute quantities of maternal
      drugs ingested over an extended period of time by a breast-feeding infant can
      alter the activity pattern of the infant's hepatic drug metabolizing enzyme
      (HDME). The HDME activity patterns of 12 breast-fed infants whose mothers were
      not on drug therapy were compared with those of 11 infants whose mothers had been
      taking 30 micrograms levo-norgesterel daily for 90 to 195 days (oral
      contraceptives group) and of 10 infants whose mothers had been taking ethambutol
      and isoniazid daily since pregnancy (tuberculosis group). As 6 beta
      hydroxycortisol in urine is considered to be a good and acceptable reflector of
      HDME activity, it was estimated from the infants' urine using enzyme-linked
      immunosorbent assay (ELISA) technique. A comparison of the patterns between 90
      days of age and 195 days of age of the infants in the control group and the two
      study groups indicated an increase from 36.6 ng/mL to 58.4 ng/mL at 195 days in
      the control group. An initial decrease from 36.6 ng/mL to 26.2 ng/mL was noted
      with commencement of maternal levo-norgesterel therapy, followed by a slow and
      steady rise to 47.8 ng/mL at 195 days of age, with a shift in the peak from 120
      to 135 days of infants age in the oral contraceptive group. A suppressed pattern
      with decreased levels of 6 beta hydroxycortisol ranging from 19.3 ng/mL to 26.5
      ng/mL at 195 days was found in the tuberculosis group. The data were analyzed by
      two-way analysis of variance (ANOVA) coupled with Duncan's Multiple range test.
      Both treatment group showed significant differences from the control group at the
      0.050 level. The HDME plays an important role in determining the final outcome of
      any drug in humans, as it controls the metabolism of drugs. Hence, alterations in
      its activity caused by the transfer of maternal drugs over a prolonged period of
      time could pose a serious problem to nurslings when they require drugs for their
      own benefit.

PMID- 8568010
TI  - A model for estimating individualized valproate clearance values in children.
AB  - To evaluate the population pharmacokinetics of valproic acid in children, 97
      steady-state serum valproate concentration measurements were gathered during
      normal, routine, outpatient care of 52 children with epilepsy (1.2-16 years of
      age). Levels were obtained from patients receiving valproate monotherapy (49%) or
      valproate with concomitant carbamazepine (32%), phenytoin (11%), or
      phenobarbitone (8%). A one-compartment model was used to fit the data with the
      Nonlinear Mixed Effects Model (NONMEM) computer program. The final model for
      clearance (L/hr) was CL = [EXP (0.022WT-1.38)] X M, where EXP = the base of the
      natural logarithm, WT = patient weight (kg) and M = a scaling factor for
      concomitant medication with a value of 1 for patients on valproate monotherapy
      and 1.61 for those receiving concomitant carbamazepine. Although phenytoin and
      phenobarbitone also were expected to increase valproate clearance, this could not
      be demonstrated, possibly because of the small number of samples taken from
      patients receiving these agents. Weight-adjusted values of valproate clearance
      decreased with increasing age. The actual mean value of 0.021 L/hr/kg for
      children taking monotherapy was slightly higher than values shown in most
      previously published reports, whereas the mean value of 0.028 L/hr/kg for
      patients taking concomitant carbamazepine was similar to those found previously
      in children taking other antiepileptic drugs.

PMID- 8568012
TI  - Insulin resistance in systemic hypertension: pharmacotherapeutic implications.
AB  - Systemic hypertension, a vascular disease with multiple origins, now is being
      linked to subtle abnormalities in glucose metabolism, which include insulin
      resistance and hyperinsulinemia. These conditions often occur together in
      patients with obesity, noninsulin-dependent diabetes, or both. Hyperinsulinemia
      and insulin resistance may cause systemic hypertension through multiple
      mechanisms. Insulin has a salt-retaining effect on the kidney. Also, insulin can
      augment catecholamine release, increase vascular sensitivity to vasoconstrictor
      substances, and decrease vascular sensitivity to vasodilator substances. In
      addition, insulin can increase production of tissue growth factors and help
      retain sodium and calcium in cells. Insulin resistance in patients can be treated
      with regular aerobic exercise, weight reduction, and a high-fiber diet.
      Pharmacologic approaches include hypoglycemic drugs, weight-reducing agents, and
      certain antihypertensive drugs that may have a favorable impact on both blood
      pressure and insulin resistance.

PMID- 8568013
TI  - First-time-in-human dose selection: allometric thoughts and perspectives.
AB  - Some of the many factors that influence dose selection in first-time-in-human
      studies are examined. These include animal toxicology, toxicokinetics, allometric
      scaling, pharmacokinetics, body surface area correlations, and integration of
      preclinical pharmacologic and toxicologic data. Appropriate preclinical
      evaluation and analysis may reduce the frequency and severity of unexpected toxic
      events arising during single-dose, phase I testing. However, significant
      intrinsic uncertainties in this process presently exist and will continue to
      exist well into the foreseeable future. With our present state of knowledge, we
      cannot provide a realistic and reasonable algorithm for ascertaining first-time
      in-human doses: any decision tree would be too unwieldy. There are several rules
      of thumb that do have a place in the evaluation and decision-making process,
      however.

PMID- 8568014
TI  - Immunopharmacodynamic studies of cyclosporine in patients awaiting renal
      transplantation.
AB  - The immunopharmacodynamics of cyclosporine were investigated in eight
      hemodialysis patients awaiting renal transplantation. Cyclosporine was
      administered orally (10 mg/kg) and intravenously (4 mg/kg), with both
      administrations separated by at least one week. Plasma samples were processed at
      37 degrees C and analyzed for specific cyclosporine and its four major
      metabolites (AM1, AM1c, AM9, and AM4N) using high-performance liquid
      chromatography. In addition, the in vitro immunosuppressive activity of these
      serial plasma samples was estimated as a relative percentage inhibition of third
      party mitogenic lymphocyte proliferation stimulated with phytohemagglutinin. The
      relationships between concentration and effect of cyclosporine versus time were
      noted. These results suggest that unchanged cyclosporine concentrations in plasma
      correlate with mitogen-induced lymphocyte suppression yielding significant
      immunosuppressant activity of cyclosporine. Control studies with plasma from
      healthy volunteers spiked with cyclosporine in the concentration range of 0
      10,000 ng/mL were developed. A sigmoidal Emax model was fitted to the effect
      versus plasma concentration data. The ratio of effect versus predicted effect
      were calculated for intravenous cyclosporine dosing. There was a good correlation
      between the observed and predicted inhibitory effect.

PMID- 8568015
TI  - Safety, tolerance, and preliminary pharmacokinetics of nefazodone after
      administration of single and multiple oral doses to healthy adult male
      volunteers: a double-blind, phase I study.
AB  - Safety, tolerance, and preliminary pharmacokinetics of nefazodone, a new
      antidepressant, were assessed in a randomized, double-blind, parallel group study
      carried out in two sequential segments: a single and a multiple daily dose
      segment. Nine subjects in the single daily dose segment were divided into three
      treatment groups and received nefazodone doses in a leapfrog fashion. Each day of
      treatment with nefazodone was followed by 2 days of placebo treatment and then
      administration of the next higher drug dose. Single doses ranged from 5-500 mg. 8
      subjects enrolled in the multiple daily dose segment were divided into two
      treatment groups. In each group, 3 subjects received nefazodone and one received
      placebo 3 times a day. Each dosage level was administered for 2 days before
      proceeding to the next higher dose from 5 mg or 10 mg 3 times a day to a maximum
      of 500 mg 3 times a day. After the dose-escalation period, the subjects in the
      multiple daily dose segment underwent a 3-day washout, after which they received
      a single dose of nefazodone at the maximum tolerated level. Safety and tolerance
      assessment involved analyses of adverse events, laboratory tests, vital signs,
      ophthalmic examinations, and ECGs. Blood and urine samples were obtained only in
      the multiple daily dose segment and analyzed for nefazodone and its two
      pharmacologically active metabolites, hydroxynefazodone and mCPP. A single blood
      sample was collected on 8 different days for assessment of trough levels (Cmin)
      and serial samples were obtained on days 5, 9, and 22 of dosing for
      pharmacokinetic profiles. Additional serial samples were also obtained after the
      last single dose of 500 mg after a 3-day washout. Nefazodone was found to be safe
      and well-tolerated in total daily doses as high as 1350 mg (450 mg 3 times a
      day). Nefazodone was rapidly absorbed after oral administration and converted to
      hydroxynefazodone and mCPP. The pharmacokinetics of nefazodone,
      hydroxynefazodone, and mCPP were found to be dose-dependent, as evidenced by dose
      normalized values of Cmin, Cmax, and AUC0-8 that progressively increased with
      dose. Although exposure of normal subjects to nefazodone and its 2
      pharmacologically active metabolites was disproportionately higher than the
      corresponding increase in dose, the safety and tolerance profiles did not show a
      parallel increase in adverse events. Nefazodone may be well-tolerated by patients
      receiving expected therapeutic doses from 200-600 mg per day when administered in
      divided doses every 8 to 12 hours.

PMID- 8568016
TI  - Comparison of the nicotine pharmacokinetics of Nicoderm (nicotine transdermal
      system) and half-hourly cigarette smoking.
AB  - Nicoderm, a nicotine transdermal system (NTS), provides a continuous, transdermal
      delivery of nicotine and is used as an aid to smoking cessation. In contrast,
      cigarette smoking yields nicotine concentrations in plasma that rise and fall
      with each cigarette. The primary objective of this study was to compare nicotine
      pharmacokinetics after treatment of subjects with either the NTS or controlled
      smoking. Fourteen healthy adult male smokers, who smoked at least 30 cigarettes
      per day, were entered into a randomized crossover design trial that compared the
      NTS, 21 mg/day applied for 24 hours, with half-hourly smoking during the day.
      Subjects abstained from smoking for 2 days, and were treated for 5 days with
      either the NTS (daily) or controlled smoking (30 cigarettes at half-hourly
      intervals on days 1 and 5; ad libitum smoking on days 2-4). Blood samples were
      obtained frequently on days 1 and 5 for analysis of nicotine and cotinine.
      Pharmacokinetic comparisons showed that nicotine Cmax, area under the curve
      (AUC)inf, and Cavg for the NTS were lower than corresponding values for
      controlled smoking; Cmax and Cavg values were approximately half those of
      smoking. Cmax and Cavg values for cotinine were similarly lower for the NTS
      compared to controlled smoking. For both treatments, plasma nicotine
      concentrations were higher on day 5 compared to day 1. Thus, the NTS provides
      concentrations of nicotine that are lower than smoking.

PMID- 8568017
TI  - Effect of food on the bioavailability of atorvastatin, an HMG-CoA reductase
      inhibitor.
AB  - To determine whether atorvastatin, a new HMG-CoA reductase inhibitor, could be
      administered with food in Phase II and III clinical trials, a nonblind,
      randomized, two-way crossover study was conducted to assess the effect of food on
      rate and extent of atorvastatin absorption. Sixteen healthy volunteers received
      single 80-mg atorvastatin capsule doses on two occasions one week apart: once
      after an 8-hour overnight fast and once with a medium-fat breakfast. The single
      80-mg atorvastatin capsule doses were well-tolerated. Mean maximum plasma
      atorvastatin equivalent concentration (Cmax) and area under the concentration
      time curve (AUC) values with food were 47.9% and 12.7% lower, respectively, than
      without food. Mean time of maximum observed concentration (tmax) and elimination
      half-life (t1/2) values were 5.9 and 32.0 hours, respectively, with food and 2.6
      and 35.7 hours, respectively, without food. A medium-fat breakfast decreased the
      rate of atorvastatin absorption significantly, but had little impact on extent of
      drug absorption. Changes in rate of atorvastatin absorption are not expected to
      have a clinically significant effect, as subsequent multiple-dose clinical
      studies have shown that dose but not plasma atorvastatin concentration profiles
      correlates with lipid-lowering effects.

PMID- 8568018
TI  - Comparison of equations for predicting bound serum concentrations of
      carbamazepine and carbamazepine-10, 11-epoxide after polytherapy in patients with
      epilepsy.
AB  - In a previous study, an equation with in vivo population binding parameters of
      carbamazepine and carbamazepine-10, 11-epoxide (CBZ-E) to serum proteins for the
      relation between unbound and bound serum concentrations was defined. A review by
      Pynnonen indicates that the average bound/unbound plasma fraction ratio is 3.0
      for carbamazepine and 1.0 for CBZ-E. In this study, the ability of equations with
      in vivo population binding parameters of the previous study (method 1) or with
      the average bound/unbound plasma fraction ratio of 3.0 of Pynnonen (method 2) to
      predict the bound serum carbamazepine concentration was retrospectively evaluated
      using 85 serum samples from 46 patients with epilepsy taking carbamazepine
      polytherapy. In 21 serum samples from 16 patients, the ability of these equations
      to predict bound serum CBZ-E concentration was also determined with in vivo
      population binding parameters from the previous study (method A) or with the
      average bound/unbound plasma fraction ratio of 1.0 of Pynnonen (method B). Mean
      prediction error, mean absolute prediction error (MAE), and root mean squared
      error (RMSE) were calculated for each method, and these values served as a
      measure of prediction bias and precision. Method 1 showed a bias to overpredict
      bound serum carbamazepine. The MAE and RMSE were significantly smaller with
      method 2 (MAE = 2.4 mumol/L; RMSE = 3.2 mumol/L) than with method 1 (MAE = 4.1
      mumol/L; RMSE = 4.8 mumol/L). Method 2 was superior to method 1 in terms of
      accuracy and precision. For bound CBZ-E prediction, method B had a bias to
      underprediction. The MAE and RMSE were smaller with method A (MAE = 0.581
      mumol/L; RMSE = 0.796 mumol/L) than with method B (MAE = 0.724 mumol/L; RMSE =
      0.905 mumol/L). Method A was superior to method B in terms of accuracy and
      precision.

PMID- 8568019
TI  - A tale of two trends: tuberculosis and typhoid fever.

PMID- 8568020
TI  - Typhoid fever in the park: epidemiology of an outbreak at a cultural interface.
AB  - The number of reported outbreaks of typhoid fever in the United States has
      recently increased. Only six were reported from 1980-1989, but seven outbreaks
      were reported in 1990. In August 1990, health officials in Montgomery County,
      Maryland, were notified of two cases of typhoid fever among persons who had
      attended both a family picnic attended by 60 persons and a Latin Food Festival
      attended by 100,000 people. We obtained interviews, blood and stool cultures, and
      Vi serologies from attendees at and food handlers for the picnic. We defined
      cases as culture-confirmed or probable. Of the 60 picnic attendees, 24 (40%) had
      cases, of which 16 were culture confirmed. Those who ate potato salad were at
      increased risk of disease (17/32 vs. 6/28, relative risk [RR] = 2.5, 95%
      confidence interval [CI] 1.1-5.4). Picnic attendees who also attended the Latin
      Food Festival were not at significantly greater risk of disease than those who
      did not, (11/22 vs. 13/38, RR = 1.5, CI = 0.8-2.7) and we found no evidence of
      disease among other festival attendees. The potato salad was prepared with
      intensive handling and without adequate temperature control by a recent immigrant
      from El Salvador who was asymptomatic, did not attend the picnic, had Salmonella
      typhi (S. typhi) in her stool, and had elevated Vi antibodies, strongly
      suggestive of the carrier state. Outbreaks of typhoid fever are a threat for
      cosmopolitan communities. While currently available control measures are unlikely
      to prevent all outbreaks, thorough investigation can identify previously
      unrecognized carriers.

PMID- 8568021
TI  - Community medicine: an urban model.
AB  - The authors examine for relevance and current application what was learned in the
      building and progress of community medicine at the Mount Sinai School of
      Medicine, from 1968 to 1993. They look back on their twenty-five years' approach
      to service development, research and education in this field, as they worked in
      an urban-based academic medical center in New York and cooperated with
      universities and their schools of health sciences abroad. A claim is made that
      this approach, whether in the United States or abroad, while fostering community
      development produces a diversity of desirable population-oriented new role models
      for the medical profession.

PMID- 8568023
TI  - Risk factors for spontaneous abortion among Saudi women.
AB  - The objective of this study was to identify important risk factors for
      spontaneous abortion (SA) among Saudi women. It was a case-control study
      conducted at King Khalid University Hospital, Riyadh, Saudi Arabia. The cases
      were 226 consecutive women hospitalized for SA between October 1992 and January
      1993. The controls were 226 consecutive women who had normal delivery in the same
      hospital during the same period. Bivariate analysis using chi-square tests and
      estimates of relative risks indicated a positive association of age at menarche
      with risk of SA (P < 0.01). Also, there was a significant higher risk of SA when
      a women was married to a blood related husband than if married to a non relative
      (RR = 2.1). The number of previous abortions was also positively related to the
      risk of SA in the current pregnancy (P < 0.01). Compared to primigravidas, the
      risk of SA was 3.2 times greater than if the outcome of the most recent pregnancy
      was also an SA. Other factors that had significant bivariate association with SA
      were a family history of SA, abdominal trauma, and infection during pregnancy.
      When multiple logistic regression was used to adjust for the effects of
      confounding variables, all the factors that showed significant bivariate
      association with SA (except outcome of the last pregnancy) remained significant.
      Early menarche may be protective, but further study is needed to confirm this.
      Greater attention should be given to pregnant women who had personal or family
      history of SA and those who had trauma and/or infection during pregnancy.
      Premarital counselling concerning consanguineous marriages is recommended.

PMID- 8568024
TI  - The role of gender, phrenology, discrimination and nervous prostration in Clara
      Barton's career.
AB  - Clara Barton was 39 years old before she became involved in Civil War
      humanitarian activities. Prior to that time, three factors shaped her personality
      and her future: phrenology gave her philosophical principles to live by,
      especially "Know Thyself"; sex discrimination on her first two jobs steeled her
      for living in a male dominated Victorian era; and psychohygienic therapy for her
      long term nervous prostration changed her behavioral approach to illness and to
      life. With these three influences in hand, Barton went on to gain world-wide
      adulation. During the Civil War, she was revered as the American Florence
      Nightingale, although she was not really a nurse. At age 55, Barton first
      embarked on the lengthy struggle to found the American Red Cross. She was
      president of the Red Cross for 23 years and rendered aid and comfort at a host of
      national and international calamities. She died at age 90 in her Glen Echo,
      Maryland home on April 12, 1912.

PMID- 8568022
TI  - A breast feeding education and promotion program: effects on knowledge,
      attitudes, and support for breast feeding.
AB  - This study was undertaken to determine the effects of a partner-support,
      incentive-based educational program on breast feeding knowledge, attitudes and
      support and to examine the relationship between feeding intentions and feeding
      behavior among low-income women. Women who expressed a willingness to participate
      in the intervention were randomly assigned to "intervention" and "usual breast
      feeding" (control) groups. Sixty-eight primipara women with expected due dates
      between May and December, 1992, volunteered to participate in the study. Of
      these, 34 were randomly assigned to each of the two groups. Approximately 81
      percent of the women completed the study, leaving n = 29 in the control group and
      n = 26 in the intervention group. The intervention consisted of special
      incentives (prizes) for women and their partners to participate in several breast
      feeding education and promotion activities. Intervention group women and their
      partners experienced positive changes in breast feeding knowledge and attitudes.
      Furthermore, the intervention seemed to have influenced more women in the
      treatment group to breast feed despite their prenatal feeding intentions. In
      addition, the partners of intervention group women were perceived to be more
      supportive of breast feeding than control group partners. These findings suggest
      that incentives, such as donated prizes, can be used to attract lower
      socioeconomic group women and their partners to breast feeding promotion
      interventions. Participation in such interventions can produce positive changes
      in breast feeding knowledge, attitudes, and support, and can have a dramatic
      effect in promoting breast feeding.

PMID- 8568025
TI  - Effects of intraruminal infusion of propionate on the concentrations of ammonia
      and insulin in peripheral blood of cows receiving an intraruminal infusion of
      urea.
AB  - To test the hypothesis that propionate can reduce hepatic capacity to detoxify
      ammonia, effects of the inclusion of propionate in intraruminal infusions of urea
      on the concentrations of ammonia, other metabolites and insulin in peripheral
      blood were investigated in two experiments with non-lactating dairy cows. Both
      experiments were of a 4 x 4 Latin square design with four animals, four
      treatments and four experimental periods of 7 d; feed was given in two equal
      meals each day, all intraruminal infusions were given for 1 h at the time of the
      morning feed, and propionic acid was partly neutralized with NaOH. In Expt 1, the
      treatments were a basal diet of pelleted lucerne and chopped hay alone or with
      the following infusions (g/d): urea 80, propionic acid 350, urea 80 plus
      propionic acid 350. The inclusion of propionate in the urea infusion markedly
      increased (P < 0.001) the concentration of ammonia in plasma compared with
      infusion of urea alone. Moreover, the inclusion of urea with the propionate
      infusion abolished (P < 0.01) the increase in blood insulin level seen with the
      infusion of propionate alone. In Expt 2, less severe treatments were imposed, the
      aim being to reproduce metabolic loads of propionate and ammonia that might be
      expected from a diet of high-protein grass silage rich in lactic acid. The
      treatments were a basal diet of grass silage alone or with the following
      infusions (g/d): NaCl 145, NaCl 145 plus urea 50, propionic acid 200, urea 50
      plus propionic acid 200. Effects were less pronounced than in Expt 1 but, in the
      period immediately after infusion, similar effects were seen. It is concluded
      that propionate-ammonia interactions may have potentially important effects on
      milk production especially for diets with high proportions of grass silage
      containing high levels of protein and lactic acid.

PMID- 8568026
TI  - Interruption of machine milking in dairy cows: effects on intramammary pressure
      and milking characteristics.
AB  - Experiments were designed to test the hypothesis that milk ejection rate
      decreases during milking, thereby causing insufficient refill of the cistern and
      decreasing milk flow rate towards the end of milking. In a first series of
      experiments machine milking of the left front quarters of 11 cows was interrupted
      for 2 min after removal of 25, 50 or 75% of expected total milk yield, while
      milking was continued in the other three quarters. Milk flow was recorded during
      machine-on times. Intramammary pressure (IMP) was recorded during premilking teat
      stimulation and during interruption of milking. IMP during interruption of
      milking decreased with decreasing amounts of milk remaining in the udder. The IMP
      did not change during these interruptions when they occurred after 25 and 50% of
      expected total milk yield was removed. Thus, the ejection rate could keep up with
      the milk flow or removal rate. However, IMP increased during interruption of
      milking following removal of 75% of total yield, although significantly so only
      in cows with a high milk flow rate. Obviously, more milk was removed than was
      transported to the cisternal cavity. It is likely that a reduced ejection rate
      caused the decreased milk flow rate. In a second series of experiments the
      pulsation ratio of the milking machine was changed from the usual 70:30 to 50:50
      with the aim of reducing the milk flow rate and thus adapting to the ejection
      rate at the end of milking. The changed pulsation ratio caused a reduced peak
      flow rate and a prolonged high milk flow period, whereas the main flow rate did
      not change significantly.

PMID- 8568027
TI  - Relationship between numbers of alpha 2- and beta 2-adrenoceptors on blood cells
      of bulls and milkability of their daughters.
AB  - Milk yield and milking time were measured on one occasion for several daughters
      (n = 6-44) from 16 bulls at morning milkings. Blood from the bulls was collected,
      and platelets and mononuclear leucocytes were isolated. The alpha 2-adrenoceptors
      on platelet membranes were identified by binding of [3H]rauwolscine, whereas for
      the determination of beta 2-adrenoceptors on intact mononuclear leucocytes,
      [3H]CGP-12177 was used. It was found that mean milk flow rate was highly
      correlated (P < 0.001) with the alpha 2-adrenoceptor densities on blood
      platelets. No correlation was found with the beta 2-adrenoceptors on mononuclear
      leucocytes. It is concluded that estimation of the alpha 2-adrenoceptors on blood
      platelets from bulls could eventually be used to investigate milking
      characteristics of cows, and might be useful in the future as a marker in genetic
      studies.

PMID- 8568028
TI  - Effects of Staphylococcus aureus products on growth and function of bovine
      mammary myoepithelial cells in vitro.
AB  - The effects of culture supernatants conditioned by the growth of Staphylococcus
      aureus M60 on in vitro growth and functional properties of bovine mammary
      myoepithelial cells were examined. Myoepithelial cell proliferation was reduced
      by Staph. aureus M60 culture supernatants. Exposure of myoepithelial cells to
      culture supernatants of isogeneic mutants of Staph. aureus M60 that produced
      either alpha or beta toxins reduced proliferation, but to a lesser extent than
      supernatants from the wild type strain. Thus, alpha and beta toxins may play some
      role in affecting myoepithelial cell proliferation. Of the cells tested, 42%
      contracted following addition of oxytocin (10(-7) M) in the culture medium.
      Treatment of myoepithelial cells for 15 min with Staph. aureus M60 supernatants,
      prior to addition of oxytocin in the culture medium, increased the number of
      cells that contracted to 92%. Exposure of cells for 3 h to the same supernatant,
      prior to addition of oxytocin in the culture medium, abolished oxytocin
      responsiveness, had no effect on immunolocalization of actin and vimentin, but
      affected the localization of alpha-actinin within myoepithelial cells. Treatment
      of myoepithelial cells for 3 h with a combination of purified staphylococcal
      proteinases XVI and XVII-B abolished oxytocin responsiveness and mimicked the
      effect of the Staph. aureus culture supernatant. We conclude that Staph. aureus
      M60 culture supernatant affected proliferation and functional properties of
      myoepithelial cells.

PMID- 8568029
TI  - Calmodulin-binding peptides isolated from alpha-casein peptone.
AB  - Peptides that inhibit calmodulin-dependent cyclic nucleotide phosphodiesterase
      were isolated from a pepsin digest of alpha-casein. Analysis of these peptides
      showed that they corresponded to the alpha S2-casein sequences 164-179 (Leu-Lys
      Lys-Ile-Ser-Gln-Arg-Tyr-Gln-Lys-Phe-Ala-Leu-Pro-Gln-Tyr). 183-206 (Val-Tyr-Gln
      His-Gln-Lys-Ala-Met-Lys-Pro-Trp-Ile-Gln-Pro-Lys-Thr-Lys-Val -Ile- Pro-Tyr-Val-Arg
      Tyr) and 183-207 (C-terminus, Val-Tyr-Gln-His-Gln-Lys-Ala-Met-Lys-Pro-Trp-Ile-
      Gln-Pro-Lys-Thr-Lys-Val-Ile-Pro-Tyr-Val-Arg-Tyr-Leu). These peptides inhibited
      calmodulin-induced cyclic nucleotide phosphodiesterase activity over the range 1
      50 microM without affecting the basal enzyme activity. These results demonstrated
      that the affinities of these peptides for calmodulin are comparable to the
      affinities of certain endogenous neurohormones and proteins that interact with
      calmodulin.

PMID- 8568030
TI  - Comparison of proteolytic activities in various lactobacilli.
AB  - A total of 169 Lactobacillus strains from 12 species (Lb. acidophilus, Lb.
      brevis, Lb. buchneri, Lb. casei, Lb. delbrueckii subsp. bulgaricus, Lb.
      delbrueckii subsp. delbrueckii, Lb. delbrueckii subsp. lactis, Lb. fermentum, Lb.
      helveticus, Lb. paracasei subsp. paracasei, Lb. plantarum and Lb. rhamnosus),
      isolated from raw milk and various milk products, and 9 Lactococcus lactis
      strains were evaluated for peptidase activities with five chromogenic substrates
      and a tryptic digest of casein. Within each species, the peptidase activity of
      the cell-free extracts of the strains varied. Furthermore, differences were
      observed between the Lactobacillus species and Lc. lactis. Lb. helveticus had by
      far the highest hydrolysing activities towards all substrates, indicating the
      presence of powerful aminopeptidases, X-prolyl-dipeptidyl aminopeptidases and
      proline iminopeptidases. Lb. delbrueckii subsp. bulgaricus possessed high
      hydrolysing activities towards substrates containing proline, alanyl-prolyl-p
      nitroanilide and prolyl-p-nitroanilide. On the other hand, Lb. fermentum and Lb.
      brevis could be considered as weakly proteolytic species. A more detailed study
      with highly proteolytic Lactobacillus strains indicated that at least three
      different proteinases or endopeptidases were present. Compared with Lc. lactis,
      the Lactobacillus strains had a much lower hydrolytic action on glutamyl-glutamic
      acid, suggesting that glutamyl aminopeptidase was absent in lactobacilli.

PMID- 8568031
TI  - Immunological and electrophoretic study of the proteolytic enzymes from various
      Lactococcus and Lactobacillus strains.
AB  - Cell extracts of various lactobacilli and two Lactococcus strains were
      investigated for their immunoresponse with monoclonal and polyclonal antibodies
      raised against various proteolytic enzymes from Lc. lactis. Except for
      Lactobacillus casei SBT 2233, none of the lactobacilli proteins showed
      immunoresponse with the monoclonal antibodies. With polyclonal antibodies raised
      against aminopeptidases N and C and endopeptidase of Lc. lactis an immunoresponse
      was observed. However, the molecular masses of the reactive bands on the blot
      were considerably different from those of the corresponding lactococcal
      peptidases, except for the band that reacted with polyclonal antibodies against
      aminopeptidase C. The polyclonal antibodies raised against X-prolyl-dipeptidyl
      aminopeptidase and tripeptidase did not show any immunoreaction. As a control,
      all antibodies reacted with the lactococcal proteins on the blot, with molecular
      masses corresponding to those reported for the proteinases and peptidases. The
      results clearly showed that most of the proteolytic enzymes of lactobacilli were
      immunologically different from those of lactococci. The proteolytic enzymes in
      the cell-free extracts were separated by non-denaturing PAGE and visualized by
      zymogram staining. The electrophoretic pattern of the proteolytic enzymes of
      lactobacilli was different from that of Lc. lactis. Both experiments indicate
      that the enzymes of the proteolytic system of lactobacilli are different from
      those of lactococci.

PMID- 8568032
TI  - Water-soluble peptides in Cheddar cheese: isolation and identification of
      peptides in the diafiltration retentate of the water-soluble fraction.
AB  - The water-soluble extract of Cheddar cheese was fractionated by diafiltration
      using 10 kDa cut-off membranes. Peptides were isolated from the diafiltrate
      retentate by chromatography on DEAE-cellulose with a linear NaCl gradient in 50
      mM-Tris-HCl. pH 8.6, and reversed-phase HPLC or electroblotting from urea-PAGE
      gels. Peptides were identified by determining N-terminal amino acid sequences and
      mass spectrometry. Most (45) of the total 51 peptides identified in the
      diafiltrate retentate originated from beta-casein, especially from a short region
      in the N-terminal half of the molecule. Only six peptides originated from alpha
      s1-casein; beta-lactoglobulin was also identified in the retentate. The origin of
      most of these peptides could be explained on the basis of known specificities of
      lactococcal cell envelope proteinases.

PMID- 8568033
TI  - Finite element micromechanical modeling of the cochlea in three dimensions.
AB  - A new cochlear modeling technique has been developed in which the number of
      assumptions required in model formulation is significantly less than in previous
      modeling studies. The main new feature of the method is that it allows individual
      cellular and membrane components of the organ of Corti to be embedded within the
      model fluid in their true structural positions, with connections to neighboring
      elements reflecting anatomical geometry. The cochlea is divided into a three
      dimensional finite element (3-D FE) network of nodes, connected by branches
      representing the local mechanical properties. The model system of simultaneous
      equations, obtained by applying continuity at each node, is solved iteratively
      using a variant of the conjugate gradient method. Here the formulation and
      implementation of the 3-D FE method are described. Force generation by outer hair
      cells is included and results are presented which demonstrate the effect of
      tectorial membrane and Deiters' cell mechanical properties on the effectiveness
      of the cochlear amplifier.

PMID- 8568034
TI  - Slopes of distortion-product otoacoustic emission growth curves corrected for
      noise-floor levels.
AB  - Distortion-product otoacoustic emission (DPE) input/output (I/O) curves were
      measured at 2f1-f2 frequencies with spectral-averaging and time-averaging
      procedures from ten normal-hearing ears. Stimuli were equal-level f1 and f2
      primary tones with f2/f1 ratios of 1.2 and f2 frequencies at 1200, 2400, and 4800
      Hz. Time-averaging procedures lowered noise-floor (NF) levels, compared to
      spectral averaging, so DPEs could be elicited by stimuli as low as 18 dB SPL in
      some ears. DPEs were corrected for power summation with NF levels and the
      resulting DPE I/O curves were fit with sixth-order polynomials. Slopes of fitted
      I/O curves were specified by the first derivative as a function of the level of
      the primary tones. Slopes of uncorrected spectrally averaged DPE I/O curves were
      strongly influenced by the NF level. Slopes of NF-corrected spectrally averaged
      DPE I/O curves were more representative of the true slope, specified as the slope
      of the corresponding time-averaged DPE I/O curve well above its NF. True DPE I/O
      slopes decreased with level from a mean slope near 1.0 dB/dB at 30 dB SPL and
      below for all three f2 frequencies. Nonmonotonicities in I/O curves were not seen
      at very low stimulus levels. At moderate stimulus levels and above,
      nonmonotonicities in individual DPE I/O curves reduced the slopes of individual
      I/O curves and reduced the average slopea cross ears.

PMID- 8568035
TI  - Preservation of amplitude modulation coding in the presence of background noise
      by chinchilla auditory-nerve fibers.
AB  - Sound envelope temporal fluctuations are important for effective processing of
      biologically relevant acoustic information including speech, animal
      vocalizations, sound-source location, and pitch. Amplitude modulation (AM) of
      sound envelopes can be encoded in quiet with high fidelity by many auditory
      neurons including those of the auditory nerve (AN) and cochlear nucleus. From
      both neurophysiological and clinical perspectives, it is critical to understand
      the effects of background masking noise on the processing of AM. To further this
      goal, single-unit recordings were made from AN fibers in anesthetized
      chinchillas. Units were classified according to spontaneous firing rate (SR) and
      threshold. Best frequency (BF) pure-tone bursts and AM (10-500 Hz) tone bursts
      were employed as stimuli at several sound levels, both in quiet and in the
      presence of a continuous wideband noise. It was found that (1) in quiet, low SR
      AN fibers show the strongest AM coding, followed in order by medium SR and high
      SR fibers, respectively. (2) AN units of all three classes generally preserve
      their AM coding even in the presence of loud (0 or +6 dB S/N) background noise
      and at high sound levels (over 75 dB SPL). (3) This preservation is usually
      achieved by lowering the average firing rate proportionately to decreases in the
      synchronous (fundamental frequency) response. (4) For a few AN fibers, the AM
      coding increases or is reduced in the presence of the background noise. These
      findings suggest that AN preservation of AM coding in the presence of a
      continuous masking noise results from shifts in the operating ranges and firing
      rates of AN fibers resulting from cochlear nonlinearities and adaptive
      mechanisms.

PMID- 8568036
TI  - Use of quantitative measures of auditory brain-stem response peak amplitude and
      residual background noise in the decision to stop averaging.
AB  - An objective quantitative approach to the decision of when to stop averaging
      sweeps in auditory brain-stem response (ABR) testing is presented. This decision
      is based on (1) the knowledge of the amplitude distributions of wave V in the
      ABRs of normal hearing individuals for varying stimulus levels, (2) calculated
      estimates of the residual background noise in the average, and (3) use of a
      quantitative statistical detector of an evoked potential. Several reasons for
      terminating an average are presented along with a specific protocol for each of
      the reasons. These protocols provide a general but consistent framework to
      address the issue of when to stop averaging and should improve the efficiency of
      ABR testing. Furthermore, it is quite possible to automate the procedure and the
      decision process.

PMID- 8568037
TI  - Olivocochlear reflex assays: effects of contralateral sound on compound action
      potentials versus ear-canal distortion products.
AB  - The strength of the olivocochlear reflex has been assayed by comparing
      ipsilateral cochlear responses with and without contralateral sound. In humans,
      ipsilateral cochlear responses have usually been inferred by measuring
      otoacoustic emissions (OAEs), whereas, in animal work, they have been assessed by
      measuring compound action potentials (CAPs). Thus reports that the reflex
      strength is smaller in humans than in animals cannot be interpreted until the
      differences between the two tests are better understood. The present study
      directly compares reflex assays using distortion-product (DP) OAE and CAP
      measures in the same animals. For ipsilateral frequencies of 2-8 kHz and levels
      from 25 to 80 dB SPL, efferent reflex strength was computed from the CAP or DPOAE
      amplitude-versus-level curves measured with and without contralateral noise. The
      "effective attenuation" produced by efferent activation was, with few exceptions,
      greater when measured with the CAP than with the DPOAE assay. Differences between
      the two measures increased as frequency increased, with differences as large as
      10 dB observed. These results, coupled with previous measurements on humans and
      animals, suggest that the efferent reflex is at least as strong in humans as has
      been shown in animal experiments.

PMID- 8568038
TI  - Adaptation-induced enhancement of vibrotactile amplitude discrimination: the role
      of adapting frequency.
AB  - Two-interval forced-choice tracking was used to measure amplitude discrimination
      for 20-Hz vibrotactile test stimuli presented to the thenar eminence of three
      human observers. For all observers, relative difference threshold could be
      decreased by adaptation to a 20- or 100-Hz stimulus. Maximal enhancement of
      discrimination occurred when the amplitude of the adapting stimulus was such that
      it excited the NP I system to approximately the same degree that the test stimuli
      did. A signal detection analysis determined that shifts in the observers'
      criteria could not consistently account for the enhancement of amplitude
      discrimination. A more likely explanation, in view of recent physiological
      discoveries, is that under optimal conditions of adaptation test stimuli
      differing slightly in amplitude become more distinctive because CNS events
      underlying the resultant sensory experiences become more refined and stimulus
      specific.

PMID- 8568039
TI  - Encoding the fundamental frequency of a complex tone in the presence of a
      spectrally overlapping masker.
AB  - A series of experiments investigated listeners' ability to encode the fundamental
      frequency (F0) of a group of harmonics (the "target") in the presence of a
      second, spectrally overlapping, group (the "masker"). Experiment 1a was a
      sequential F0 discrimination task between two targets, whose F0s were
      geometrically centered on 210 Hz, in the presence of a 210-Hz masker. The target
      and the masker were bandpass filtered identically, either from 20 to 1420 Hz
      ("low-frequency" condition) or from 3900 to 5400 Hz ("high-frequency" condition).
      In the low-frequency condition the masker affected performance only moderately,
      regardless of whether it was gated synchronously with, or was turned on 150 ms
      before and off 150 ms after, each 200-ms target. In the high-frequency condition,
      the synchronous masker also had a moderate effect, but the asynchronous masker
      reduced performance dramatically. Whatever the masker gating, listeners did not
      hear the combination of the masker and target in this region as a mixture of two
      complex tones, but experienced a unitary noiselike or "crackle" percept.
      Experiment 1b showed that the large deterioration seen in the high-frequency
      condition of experiment 1a could be obtained in the low-frequency condition by
      reducing the F0 to 62.5 Hz, suggesting that the resolvability of adjacent
      harmonics was important for the effect. Experiment 2 required listeners to detect
      a difference in F0 ("delta F0") between two simultaneous groups of components,
      one filtered in the high region and the other in the low region. Performance was
      only slightly degraded by a continuous masker filtered in the low region, but was
      reduced to chance by a masker in the high region. Experiment 3 showed that, as
      the delta F0 between a masker and a target in the low region increased from 1% to
      8%, listeners identified the mixture as sounding progressively "less fused," but
      this was not the case in the high region. It is concluded that listeners are poor
      at extracting the F0s of two groups of unresolved harmonics in the same frequency
      region. The experiments provide no evidence that listeners can use the leading
      part of an asynchronous masker to identify its F0 and thereby help extract the
      target's F0 from the mixture.

PMID- 8568040
TI  - Masker asynchrony impairs the fundamental-frequency discrimination of unresolved
      harmonics.
AB  - A series of experiments investigated the finding that the fundamental frequency
      (F0) discrimination of a group of unresolved harmonics (the "target") is impaired
      more by a masker which starts before and ends after it than when the masker and
      target are gated on and off together [Carlyon, J. Acoust. Soc. Am. 99, 517-524
      (1996)]. Generally, the masker was a group of unresolved harmonics with an F0 of
      210 Hz, the target F0s were geometrically centered on 210 Hz, both the targets
      and the masker were filtered between 3900 and 5400 Hz, and the target duration
      was 200 ms. The additional deterioration produced by the portion of the masker
      occurring before the target (the "forward fringe") was greater than that produced
      by the portion after the target ("backward fringe"), but both had some effect.
      The forward and backward fringes reduced sensitivity even when the portion of the
      masker synchronous with the targets was absent, although the reduction was
      greatest when it was present. The deterioration was markedly reduced by filtering
      the fringes into a frequency region remote from the target and the synchronous
      portion of the masker, by attenuating the fringes by 10 dB, or by presenting them
      either contralaterally to the target or diotically. It could not be reduced by
      allowing the F0 of the fringes and of the synchronous portion of the masker to
      differ greatly from that of the target, or by adding a low-frequency portion to
      the fringe, thereby providing an additional cue to the time of transition between
      fringe and target. Explanations based on peripheral adaptation and on seemingly
      similar effects previously observed with brief targets [Massaro, J. Acoust. Soc.
      Am. 58, 1059-1065 (1975); Kelly and Watson, J. Acoust. Soc. Am. 79, 1934-1938
      (1986); Divenyi and Hirsch, Percept. Psychophys. 17, 246-252 (1975)] were
      rejected. The data are discussed in terms of a central mechanism which includes
      parts of the fringes in its estimate of the pitch of the target/masker mixture.

PMID- 8568041
TI  - Across-frequency processing of multiple modulation patterns.
AB  - This study sought to determine the degree to which the auditory system can
      perform simultaneous across-frequency analyses on concurrent, but independent,
      modulation patterns. This was tested by measuring detection of a multicomponent
      signal presented against a background comprised of multiple modulation patterns.
      The results indicated that independent comodulation masking releases (CMRs) could
      occur simultaneously, but only if the independent modulation patterns were
      restricted to relatively discrete frequency regions. Moreover, the analysis
      accomplished in each region did not appear to be optimal. This suggests that
      there are limits to the independence with which simultaneous across-frequency
      analyses can be performed.

PMID- 8568042
TI  - The probe-signal method and auditory-filter shape: results from normal- and
      hearing-impaired subjects.
AB  - In the probe-signal method, subjects are required to detect a signal in noise
      that is presented on the majority of trials at an "expected" (target) frequency
      but on a minority of trials at an "unexpected" probe frequency. Detection of the
      probes worsens with increasing separation between the target and probe
      frequencies. This result has often been interpreted as indicating that subjects
      monitor the output of a single auditory filter centered at the target frequency.
      To test this idea, a two-stage experiment was conducted. In the first stage,
      auditory-filter shapes were estimated using the notched-noise method at center
      frequencies of 1000, 1259, 1585, and 2000 Hz. These were the frequencies that
      were used for the targets in the second stage of the experiment. In the second
      stage, low-pass filtered white noise was presented continuously. On each trial, a
      cue tone was presented at one of the four possible target frequencies. The
      specific frequency was selected randomly on each trial. This was followed by two
      observation intervals during one of which a further sinusoidal tone was
      presented. This tone was either a target (the same as the cue frequency) (on 60%
      of trials), or had one of four possible probe frequencies corresponding to that
      target. The four probe frequencies were chosen to correspond to specific points
      on the estimated response curve of the auditory filter centered at the target
      frequency. The percentage of correct detections of a given probe was compared
      with that obtained in a separate condition where the frequency of the tone was
      fixed throughout, the cue frequency always equaled the target frequency, and the
      target was attenuated by an amount corresponding to the attenuation of the
      auditory filter at the probe frequency. Two subjects with normal hearing and two
      subjects with unilateral cochlear hearing loss were used. Comparison of the
      results for the normal and impaired ears suggests that the detectability of the
      probes is governed more by the selectivity of the auditory filters than by the
      ratios of the expected and probe frequencies. However, detection of the probes
      was generally better than would occur if subjects monitored the output of a
      single auditory filter centered at the target frequency.

PMID- 8568044
TI  - On the pitches of the components of a complex tone.
AB  - The pitches of the harmonics (numbers 1, 2, 3, 4, 5, 7, 9, and 11) of a complex
      tone were measured in a matching experiment. The harmonics to be matched were
      mistuned (8% or less) either positively, or negatively, or not at all. For all
      mistuned harmonics and all listeners the matching pitches were found to be
      exaggerations of the mistunings, i.e., the data exhibited pitch shifts with the
      same sign as the mistunings. This result is shown to be contrary to place models
      of pitch perception, such as the spectral pitch algorithm of Terhardt, in which
      pitch shifts are caused by the interaction of excitation patterns for the
      individual harmonics. An alternative model, in which pitch is determined by
      neural timing, also fails to account for the data. However, a hybrid model,
      combining effects of excitation pattern interaction with neural timing, does
      agree with most of the data.

PMID- 8568043
TI  - Detection of frequency changes in transposed sequences of tones.
AB  - The ability to detect frequency changes in transposed sequences of tones was
      examined in a series of seven experiments. Listeners were asked to judge which of
      two transposed (i.e., frequency-shifted) comparison patterns preserved the
      sequence of relative frequencies presented in a preceding standard pattern. The
      task was performed with five-tone and two-tone patterns under conditions of high
      and minimal pattern uncertainty. Regardless of pattern length or level of
      uncertainty, frequency discrimination thresholds for a change in the relative
      frequency of a single tone were considerably higher when patterns were transposed
      than when they were not. There was a tendency for performance to worsen with
      increasing degrees of transposition (primarily under high uncertainty) but most
      of the detrimental effects of transposition occurred within the first two
      semitones of transposition. Minimal uncertainty testing resulted in large
      improvements with five-tone patterns (as much as one order of magnitude), but
      there was no effect of level of uncertainty on performance with two-tone
      patterns. Thresholds for changes in two-tone patterns were similar to (although
      slightly higher than) those for five-tone patterns under minimal-uncertainty
      testing. This pattern of results reveals that the effects of stimulus complexity
      (sequence length) and pattern familiarity (level of uncertainty) on relative
      frequency discrimination are quite similar to the effects of these variables on
      absolute-frequency discrimination.

PMID- 8568045
TI  - Observer weighting of concurrent binaural information.
AB  - Two experiments examined how listeners weight binaural information of individual
      components in a multicomponent complex when they are instructed to use this
      information in various ways. On each experimental trial of the first experiment,
      a two-component complex consisting of a 553- and 753-Hz pure tone was presented
      to listeners over headphones. Each component had an interaural difference of time
      (IDT) that was randomly chosen from a single distribution. Listeners were to
      indicate the apparent position of the intracranial image relative to the midline
      on the basis of either the IDT of the 753-Hz component, the sum of the IDTs of
      the two components, or the difference between the two IDTs. Observer weights for
      the component IDTs were derived by computing the point-biserial correlations
      between the IDTs of the components and the listeners' left-right judgments. Three
      of the four listeners were found to adjust their weighting of the binaural
      information appropriately for each listening task, while the fourth listener
      consistently gave almost no weight to the 553-Hz component regardless of the
      listening condition. In a second experiment, listeners were instructed to attend
      to the randomly selected IDT of one of three components (553, 753, or 953 Hz) and
      to indicate whether the intracranial image produced by that component was to the
      left or right of midline. Only one of six listeners gave greatest weight to the
      target component regardless of its frequency. The other five listeners gave
      significant weight to all three components in all listening conditions. In all
      cases, individual differences in percent correct performance could be attributed
      largely to individual differences in weights with little variation in internal
      noise.

PMID- 8568046
TI  - Some effects of filtered contexts on the perception of vowels and fricatives.
AB  - When a phrase is filtered to simulate the effects of a transmission channel, a
      vowel played shortly afterward is heard as if there is perceptual compensation
      for the filter. However, a transmission channel would also have an effect on
      sounds that arrive after the vowel. The present experiments ask whether vowel
      test sounds are affected by the filtering of a subsequent affricate when there
      are no other sounds present. Effects on other types of test sounds from different
      subsequent sounds are measured as well. The experiments also ask whether these
      effects occur when there is information about the channel in a precursor phrase.
      Listeners identified words from continua between /It integral of/ and /epsilon t
      integral of/, /aept/ and /[symbol: see text]/, or /[symbol: see text]/ and
      /[symbol: see text]/. Filters' frequency responses were the difference of
      spectral envelopes from the end-point test sounds. The perceptual midpoints of
      all the continua were shifted in a manner consistent with compensation when the
      precursors were filtered, as well as when sounds subsequent to the test sound
      were filtered and there were no precursors. Also, when filtered precursors were
      present, the shifts increased when filtering was added to sounds subsequent to
      the test sound. These results indicate that mechanisms of perceptual compensation
      for filtering by transmission channels use information in preceding sounds in
      combination with information in following sounds and that these mechanisms
      operate between different types of speech sounds.

PMID- 8568047
TI  - Task dynamic and articulatory recovery of lip and velar approximations under
      model mismatch conditions.
AB  - An algorithm for recovering task dynamics and speech articulator movements from
      speech acoustics was tested under various model mismatch conditions. There was
      evidence of articulatory compensation to recover tract-variable (constriction)
      trajectories in speech produced with a lip approximation under sufficiently
      constrained conditions. However, in more extensive studies of lip and velar
      approximations, the recovered tract-variable trajectories were also different
      from those of the data-producing utterance. This phenomenon can occur because the
      matching criterion in the analysis-by-synthesis procedure is an acoustic
      criterion and the correspondence between the tract-variable trajectories and the
      acoustic output is not exact. While there may be some tract-variable compensation
      to attain a good acoustic match, there is evidence of a correspondence between
      how well the tract-variable trajectories match and how well the formant
      frequencies match in particular instances.

PMID- 8568048
TI  - A robust sequential test for text-independent speaker verification.
AB  - A robust speaker verification algorithm based on sequential hypothesis testing is
      presented. In speaker verification, the system performance is severely degraded
      by deviations from the nominal statistical speaker models caused by insufficient
      training data, varying microphone and transmission line characteristics, and
      different levels and types of background noise. Historically, this problem has
      been addressed by using an empirical method to determine an adequate decision
      threshold for a desired operating point. The robust detection algorithm presented
      here is based on a minimax criterion, such that the worst-case performance over a
      class of distributions is minimized. The sequential test provides further
      robustness by using additional data if a decision cannot be reached with the
      desired level of confidence. The sequential detector has been implemented and
      tested on a realistic database collected specifically for this purpose, and the
      performance has been shown to be comparable to or better than that of the
      corresponding heuristic detectors previously described in the literature.

PMID- 8568049
TI  - Deputed power of medical control: the hidden message in the ritual of oral shift
      reports.
AB  - The exchange of oral shift reports between nurses is a prominent part of the
      everyday routine in a hospital ward. Increased awareness of the more or less
      explicit functions of such communication is likely to have a positive impact on
      the nursing profession. Oral shift reports in a nursing care system based on task
      allocation were therefore observed and analysed. Using an ethnographic approach,
      reports were tape-recorded, and nurses were interviewed regarding their
      experiences. During the shift report session, the nurses were found to receive
      ritually mediated deputed power of medical control from their colleague, but
      little attention was paid to nursing needs and measures. The nurses clearly
      demonstrated that they were caught in a system dominated by a medical paradigm
      that effectively obstructed the progress of nursing as a professional discipline
      in its own right.

PMID- 8568050
TI  - The Legacy of War: conference organized by the Royal College of Nursing History
      of Nursing Society at the Cowdray Hall, London, England, on 30 May 1995.

PMID- 8568051
TI  - Multidisciplinary collaboration: life line or drowning pool for nurse
      researchers?

PMID- 8568052
TI  - Need for action against tuberculosis.

PMID- 8568053
TI  - UK estimate of children affected by HIV.

PMID- 8568054
TI  - The family dynamics of childbearing and childrearing families in Finland.
AB  - Within the context of an international comparative family dynamics project, this
      study had two chief goals: to describe the family dynamics of childbearing and
      childrearing families in Finland, and to study changes in family dynamics after
      childbirth. The sample consisted of families expecting (n = 118) and rearing (n =
      94) their first or second child in Finland. Two instruments were used in data
      collection, i.e. the Family Dynamics Questionnaire and the Family Dynamics
      Measure; both these tools have been developed in the USA. According to the
      results, childbearing and childrearing families were thought to function quite
      well. Pregnant mothers described their family dynamics in more positive terms
      than fathers, reporting greater flexibility and clearer communication. Similarly,
      mothers reported more individuation and mutuality than their partners. First-time
      expectant families reported more mutuality than families expecting their second
      child. Childrearing mothers reported more individuation, but also more role
      conflict than did fathers. Communication in families rearing their first child
      was clearer than in families rearing their second child. The birth of a child
      affected family dynamics by bringing about various changes such as role conflict,
      isolation and distorted communication.

PMID- 8568055
TI  - Governing childbirth: the wider view.
AB  - This paper seeks to 'problematize' the British government's wider intentions for
      public health, as they are shaped by free-market economics and technological
      medicine. A variety of epidemiological studies have revealed evidence of
      declining health among low socio-economic populations who are particularly
      affected by economic and social changes. The government is responding to the
      potential crisis by targeting specific groups of the most visible and costly
      victims of public ill-health. Recipients of health care with a lower public
      profile, such as pregnant women, are being subjected to the same policy. Current
      governmental strategies are regarded as an example of a medically oriented
      approach that focuses on special strategies for pregnancy and birth but ignores
      the long-term requirements for public health.

PMID- 8568056
TI  - Breastfeeding duration: prenatal intentions and postnatal practices.
AB  - A study of 78 primiparas examined the role of prenatal intent and postnatal
      experiences in breastfeeding duration. Those fully breastfeeding 3 months after
      the birth of the baby had a higher level of education, timed their decision to
      breastfeed earlier, intended to breastfeed longer and had a more negative
      attitude to formula feeding. Commitment and confidence scores were not related to
      breastfeeding duration in first-time mothers. Breastfeeding duration was also
      related to the timing of the first breastfeed and extent of mother-infant contact
      in the 72 hours after birth but not to the number of feeding problems.

PMID- 8568057
TI  - Social support: how does it really work?
AB  - This study examines social support effect on stress and adaptation through the
      mediating effect of control. Participants in the study were 12 male and 65 female
      rheumatoid arthritis patients who were being treated in the outpatient clinics of
      three large hospitals in Israel. Findings suggest that social support did have a
      significant effect on stress and adaptation, though this effect was through the
      mediating effect of control and not as a buffer as was suggested previously.
      Implications of the results for nursing science are discussed.

PMID- 8568058
TI  - A study to identify the attitudes and needs of qualified staff concerning the use
      of research findings in clinical practice within mental health care settings.
AB  - In 1972 the Report of the Committee on Nursing recommended that nursing should
      become a research-based profession. Although, it is acknowledged that research
      has made a significant contribution to the body of nursing theory since then, it
      has had little impact on clinical practice. The present study is a small
      exploratory survey to assess the attitudes and needs of qualified nurses working
      within mental health care settings concerning the use of research findings in
      practice. A total of 150 questionnaires were sent to trained nurses working
      within a defined geographical area in the south-east of England and 118 were
      returned, giving a response rate of 78%. The main findings suggest that although
      the vast majority of nurses in the study have a very positive attitude towards
      research, very few actually make significant use of research findings to enhance
      their clinical practice. Some of the variables that seem to contribute to this
      state of affairs are: lack of the necessary research appreciation skills to
      critically evaluate research findings and apply them in practice; not enough
      relevant research studies available in the clinical areas; and inadequate support
      from managers. However, most of the nurses in the study said that they would be
      involved with research activities if the time was provided for them to do so.

PMID- 8568059
TI  - The relationship between a medium secure environment and occupational stress in
      forensic psychiatric nurses.
AB  - The present study investigated occupational stress levels in forensic psychiatric
      nurses within a medium secure unit for mentally disordered offenders and examined
      the possible relationships between aspects of the ward environment and identified
      stress levels. Data were obtained through self-report measures and unit
      statistics using a sample of 38 nurses on two secure (high and medium) wards. No
      significant differences in levels of occupational stress or perception of ward
      environment were observed between nurses on the two wards. Global ward atmosphere
      scores were compared with those of a maximum secure facility in the USA, showing
      the unit to be highly therapeutic. Occupational stress scores for all nurses were
      compared with normative regional data and showed elevated scores on broad view of
      control, satisfaction and type A behaviour. No demographic or ward environment
      variables were found to be associated with these high scores. Interpretations and
      implications are discussed.

PMID- 8568060
TI  - Nursing leaders' and nurses' view of health.
AB  - This study is part of a scientific project, 'Multidimensional Health', the main
      goal of which is to introduce a broad view on health into health care and
      nursing. The purpose of this study is to examine the view of health among nursing
      leaders and members of caring staff and to compare it to that of patients (a
      previous study in the project). The study is based on K. Eriksson's theory of
      caring and its view of the human being with a body, soul and spirit, and health
      as a dynamic process concerning all aspects of human life. An inquiry form with
      open questions that brought to the fore various aspects and dimensions of health
      was filled in by 20 nursing leaders and was used in interviewing 49 nurses.
      According to the results many aspects of life are contained in the concept
      'health'. Health is above all an experience of well-being. Ways of promoting
      one's health are described in terms of various 'healthy' living habits and
      preventive measures. A supporting and humane attitude is hoped for in others.
      There is unanimity that feelings affect health. Belief may have a positive
      influence on health. The meaning of life is connected with health. Even suffering
      is part of health. In interpreting the answers we assume three dimensions of
      health. 'Health as behaviour' connects health with living in a healthy way.
      'Health as being' would mean a state of health and is characterized by a search
      for some kind of balance in one's inner state. 'Health as becoming', growing
      towards health, means that a person becomes whole on a higher level of
      integration.

PMID- 8568061
TI  - Nurses' knowledge and beliefs about AIDS: comparing nurses in hospital, community
      and hospice settings.
AB  - The literature reports an ongoing debate amongst nurses regarding the risk of
      contracting human immunodeficiency virus (HIV) through routine nursing care. An
      emotionally charged dilemma appears to exist for many nurses regarding what they
      perceive as conflict between professional obligation and personal risk. This
      study investigates nurses' beliefs, knowledge and perceptions of risk of
      contracting HIV while implementing their nursing care. The study focuses on
      qualified nurses in the hospice, hospital and community settings. No other
      similar comparative study that also focuses on hospice nurses has been
      identified. This quantitative study was implemented within Northern Ireland, by
      way of a respondent-administered questionnaire. The study's sample consisted of
      45 qualified nurses and a response rate of 93% (42 respondents) was achieved.
      Analysis of the data involved the use of descriptive and correlational
      statistics. Overall findings indicated that many nurses, but particularly those
      who work in the hospital and community settings, hold negative and biased
      beliefs, and have inadequate knowledge and misguided perceptions regarding their
      risk of contracting HIV through the implementation of routine nursing care of
      clients. Many of those nurses readily admit their lack of knowledge. On the
      whole, hospice nurses appear more knowledgeable and exhibit a more positive
      approach to AIDS clients, and appear less fearful than do nurses in the other two
      settings. Implications for hospital management, for nurse education, for nurses
      themselves and for clients are discussed. This study should be seen as a
      springboard for future research within Northern Ireland.

PMID- 8568062
TI  - How do nurses inspire and instil hope in terminally ill HIV patients?
AB  - In this study the researcher examined how nurses inspire and instil hope in
      terminally ill HIV patients. The study therefore focuses on the interventions,
      attitudes, principles and process utilized by nurses working within a liaison
      psychiatry unit where in-patient care for terminally ill HIV patients is
      available. Using grounded theory methodology, the data were coded and analysed,
      producing an integrated theory of hope inspiration, comprised of four core
      variables: reflection in action; affirmation of worth; creating a partnership;
      and the totality of the person. The researcher postulates that hope is inspired
      in terminally ill HIV patients by means of nursing the totality of the person
      within the context of a formed partnership, underpinned by the affirmation of the
      individual's worth, which is assured by the nurse entering into the process of
      reflection in action. The researcher further suggests that hope inspiration is
      inextricably linked to effective nursing practice, and is interwoven with the
      concepts of nursing, caring and helping.

PMID- 8568063
TI  - Feminist research: its relevance to nursing.
AB  - It is the author's intention to explore feminist research and discover its
      relevance to nursing practice. In order to achieve this, definitions of feminism
      and feminist research will be made. From these it will be possible to place the
      feminist research process within a historical context to further understand its
      focus. Then an analysis of feminist research will be made, examining feminist
      epistemology, feminist methodology and the methods used by feminist researchers.
      At this point an examination of who should or can do feminist research will be
      made, followed by a discussion about the validity of feminist research.

PMID- 8568064
TI  - Hysterectomy: British National Health Service and private patients have very
      different experiences.
AB  - One in five women in the United Kingdom will have a hysterectomy by the time they
      reach the age of 65. This paper explores the experiences of women as they seek
      advice in outpatient clinics, as they go into hospital for surgery, and as they
      return home to convalesce. Differences in doctor-patient communication between
      private sector and National Health Service patients are discussed. The results of
      this study point to the inadequacy of current practice in providing information
      to patients about this potentially serious operation.

PMID- 8568065
TI  - Some surprising similarities in the clinical reasoning of 'expert' and 'novice'
      orthopaedic nurses: report of a study using verbal protocols and protocol
      analyses.
AB  - This paper reports on an Australian study of 'expert' and 'novice' orthopaedic
      nursing practitioners' clinical reasoning. Concurrent and retrospective verbal
      reports of patient assessment and care planning in real 'everyday' practice
      situations were collected from nine pairs of 'expert' and 'novice' orthopaedic
      nurses. Verbal protocol analyses revealed that the experts used the same level of
      concepts as novices, that their clinical reasoning was as physically orientated
      as that of novices, and that the implicit constructions of nursing in the
      reasonings of both experts and novices were consistent with a 'medical model' of
      health care. The research design, limitations and findings are discussed.

PMID- 8568066
TI  - The nature of ophthalmic services, and the education and qualifications of
      nurses: a national survey.
AB  - This paper reports on a national survey undertaken by the Royal College of
      Nursing (RCN) Ophthalmic Nursing Forum to assess, first, the nature of ophthalmic
      services and, second, skill-mix and educational opportunities of nurses working
      with ophthalmic patients. A questionnaire was formulated and tested by members of
      the committee, with research and statistical support from the School of Nursing
      Studies, University of Manchester. The questionnaire was sent to the total
      population of ophthalmic units/hospitals in the UK (n = 168). Following
      descriptive statistical data analysis it was concluded that in smaller units,
      that is those with less than 18 beds (NB mean number of beds = 18), less than one
      in four nurses holds an ophthalmic qualification. Some respondents identified
      that in 10 instances no nurses held an ophthalmic qualification and that on 12
      further occasions only one nurse held a relevant ophthalmic qualification. There
      are insufficient numbers of nurses holding ophthalmic qualifications. The
      implications of this situation are discussed and recommendations made.

PMID- 8568067
TI  - Cardiac nurses' preparedness to use self-help groups as a support strategy.
AB  - Self-help groups are lay, mutual support groups in which people who share some
      long-term existential problems in their lives meet regularly to support each
      other empathetically. These groups can be viewed as supplementary sources of
      support outside patients' existing social networks. As such, it is of importance
      to be aware of them when planning nursing care. The aim of this study was to
      examine cardiac nurses' preparedness to use self-help groups as a support
      strategy. A qualitative research method was used and 12 registered nurses from
      two coronary care units were interviewed. The findings showed that nurses
      knowledge of social support, self-help groups and of patients' social
      circumstances as well as their attitudes to their own roles as nurses were of
      importance in their preparedness to use self-help groups as a support strategy.
      Lack of knowledge of social support and self-help groups affected the nurses'
      attitudes towards lay care and was probably the reason for not using self-help
      groups as a support strategy. Most of the nurses were well informed about their
      patients' social circumstances, they had an explicit family nursing approach and
      were not at all against further expansion of their nursing role. However, there
      is a need for education in innovative ways of working that respond to and
      interact with informal support networks if nurses are to be able to contribute to
      empowerment of their patients.

PMID- 8568068
TI  - A study of the perception and experiences of critical care nurses in caring for
      potential and actual organ donors: implications for nurse education.
AB  - This paper describes a research study designed to explore the knowledge,
      perceptions and attitudes of practising critical care nurses towards caring for
      'brain stem dead' cadaver organ donors and their families. The influence of
      formal nurse education and experiential learning were investigated together with
      what nurses felt could better prepare them for this role. Data were collected
      through self-completion questionnaires from 103 critical care nurses. This was
      instrumental in forming a semi-structured interview schedule whereby seven
      respondents were interviewed. The findings of the study suggest that nurses are
      very favourable towards organ donation and this correlated with their knowledge
      of brain stem death (P < 0.024). Nurses with between 6 and 10 years critical care
      experience had a significantly higher knowledge base (P < 0.05) than those of
      less or greater experience. Nevertheless, when challenged some nurses were less
      comfortable with the concept of brain stem death and caring for these patients. A
      degree of cognitive dissonance was identified. Discussion revealed that all
      nurses need to have a better understanding of their role in organ donation, no
      mater what nursing discipline they practice. This may help to expel some of the
      myths that have, undeservedly, become established and given the donor process a
      rather sinister image.

PMID- 8568069
TI  - Diabetes: an adolescent's perspective.
AB  - The personal meaning and perceived impact of insulin dependent diabetes mellitus
      (IDDM) were investigated in an exploratory study of 51 Finnish adolescents aged
      between 13 and 17. Interview data were examined using continuous comparative
      analysis. The personal meaning of IDDM was described using the following
      categories: a habit; a little devil; a nightmare; stress; prison; death; and
      hell. A core concept to emerge was that of control. Young people felt IDDM
      controlled, or limited, their freedom and independence. Two main themes emerged
      in terms of the impact of IDDM in the lives of adolescents: a threat to life's
      equilibrium and a healthy lifestyle. Diabetes was viewed as a threat to physical,
      psychological and social well-being which disrupted the balance of life. In
      contrast, the other main category, a healthy lifestyle, revolved around the
      notion that having IDDM offered a unique opportunity to live a healthy life. The
      results provided a useful insight into the personal meaning of IDDM and serve to
      raise awareness of the problems and difficulties experienced by adolescents with
      this condition.

PMID- 8568070
TI  - Dyspnoea: a study of measurement instruments for the assessment of dyspnoea and
      their application for patients with advanced cancer.
AB  - Dyspnoea or breathlessness is a problem commonly encountered in the palliative
      care of many patients with advanced cancer, although its impact on the patient is
      frequently under-estimated. In advanced cancer, the aim of effective management
      is to minimize the patient's perception of breathlessness which, in turn, depends
      on reliable assessment. Most of the knowledge and experience of dyspnoea has been
      acquired through working with patients with chronic pulmonary disease and there
      is a dearth of literature relating specifically to the assessment of dyspnoea in
      advanced cancer. A critical analysis of available literature was undertaken and
      measurement instruments available for assessing breathlessness and their
      application to dyspnoeic patients with advanced cancer were reviewed. Dyspnoea is
      a complex, multidimensional sensation and its subjectivity makes it difficult to
      quantify. For patients with advanced cancer, dyspnoea may be one of many symptoms
      and measurement instruments need to take this into account. No single measurement
      instrument takes into account the different components of dyspnoea and as the
      final choice will depend on the purpose of assessment, it is likely that more
      than one instrument will be required.

PMID- 8568071
TI  - Unbearable incidents: failure to endure the experience of illness.
AB  - Inherent in the illness experience are multiple assaults on one's self and one's
      body. These assaults may be interpersonal (such as an unwitting remark made from
      another), or intrapersonal (such as unrelenting symptoms that are a part of
      illness, injury or treatments). These assaults may accumulate until the situation
      becomes unbearable, the person can no longer 'take it', and the person loses
      control. In this paper, the authors examine the circumstances that resulted in
      the breakdown of endurance, and noted that while some of the factors remained
      unbearable, others are managed. The authors suggest that the patient's response,
      that is 'loosing it', may be beneficial. 'Losing it' is a means of ensuring
      changes in care for a patient, or aids in the relinquishment of unrealistic
      expectations of one's self and one's future. In all instances, however, the
      patient's plan of care should be carefully examined and, if necessary, modified.

PMID- 8568072
TI  - Patient-centred evaluation and rehabilitative care.
AB  - The evaluation of health care outcomes is becoming increasingly important in
      today's health service. The wide range of measures used to evaluate these
      outcomes often makes clinical audit difficult and the comparison of research
      papers almost impossible. In this paper we will discuss some of the issues
      surrounding outcome measurement in rehabilitative care, examine one of the most
      commonly used outcome measures from this area (the Barthel Index) and consider
      Goal Attainment Scaling, a technique which offers both clinicians and researchers
      the opportunity to evaluate health care outcomes on the basis of patient-centred
      practice. We have identified certain methodological problems that need to be
      addressed if Goal Attainment Scaling is to become an acceptable measure in the
      area of physical rehabilitative care.

PMID- 8568073
TI  - A view from somewhere: the presence and function of religious commitment in
      nursing practice.
AB  - As western society becomes increasingly pluralistic, nurses are confronted by
      fundamental controversies, such as those moral, philosophical or religious in
      nature. One strategy to deal with such pluralism is to dismiss a nurse's
      fundamental moral, philosophical or religious commitments as unprofessional bias.
      In this paper, however, I would like to analyse the presence and function of
      religious commitment, in particular to see if it could have a justified and
      relevant function in nursing care. This function will be elicited by interpreting
      nursing care as a practice and applying a certain theory of theorizing, focusing
      on the function of 'control beliefs', of which professionalism is one particular
      set.

PMID- 8568074
TI  - Humanism and positivism in nursing: contradictions and conflicts.
AB  - Nursing and nurse education have been influenced by a shift towards a broadly
      humanistic philosophy as a basis for practice. At the same time, in attempts to
      develop a knowledge base and credibility as a profession, the vital importance of
      research has been acknowledge. Both these aspects of nursing are increasingly
      forming the basis for all nursing courses. However, in this paper, it is argued
      that the implicit adoption of notions of science based in a positivistic paradigm
      gives rise to conflicts with a humanistic philosophy. It is contended that
      nursing has inherited a 'legacy of positivism', which promotes objectivity and
      reductionism and which excludes subjective meaning and the personal from the
      research process. In part this has been due to the powerful influence of medical
      hegemony, which has defined the nature of legitimate knowledge and controlled
      nursing research through the gatekeeping function of doctors. If nursing is to
      make progress in the development of a knowledge base, the contradictions between
      humanism and positivism must be acknowledged as a barrier to an integration of
      the art and science of nursing. This paper suggests that what is required is a
      paradigm shift, a redefinition of nursing science, which not only rehumanizes the
      nature of research, but also refutes and challenges the notion of objectivity and
      the objective attitude.

PMID- 8568075
TI  - Evaluating individual performance in higher education: a new challenge for nurse
      educators.
AB  - In response to the demands for more accountability and efficiency in higher
      education, of which nurse education is now a part, this paper explores the
      evaluation of individual performance. It considers the purposes of staff
      appraisal and draws upon a study of criteria for self-appraisal of teachers and
      upon experience gained in introducing teacher appraisal into schools. Different
      teaching environments are discussed and the additional demands upon academic
      staff in universities in terms of research are considered in the light of the
      recent Research Assessment Exercises. Particular consideration is given to the
      performance of nursing departments in the 1992 exercise and to the implications
      for staff appraisal. Successful procedures for evaluating individual performance
      in schools that might transfer to higher education are identified and strategies
      that might be adopted by nursing departments are suggested. This paper argues
      that evaluation of individual performance is a worthwhile departmental function
      which, when successful, may help to create an atmosphere more conductive to the
      eventual successful introduction of total quality management to the institution
      as a whole. It concludes that the extra substantial demands upon staff time and
      energy, at a time when nursing departments are trying to establish themselves in
      the higher education sector, might be alleviated if the groundwork already
      undertaken in schools is put to good use.

PMID- 8568076
TI  - Analysing qualitative interview data: addressing issues of validity and
      reliability.
AB  - Over the last 20 years qualitative research methods have increased in popularity
      in the field of nursing research, yet critical issues of validity and reliability
      are often overlooked in published research reports. Thus, the aim of this paper
      is to describe the steps which the author followed to address issues of rigour in
      one qualitative research study. The study was conducted to explore the health
      visitor's role in identifying and working with vulnerable families in the
      community in relation to child protection. This paper will focus on how issues of
      validity and reliability were addressed in terms of qualitative interview data.

PMID- 8568077
TI  - A hermeneutic study of the experiences of relatives of critically ill patients.
AB  - This paper describes a hermeneutic study of experiences of relatives of
      critically ill patients in the context of a large tertiary referral hospital in
      Sydney, Australia. The participants were 15 female family members of critically
      ill patients. Taped conversations between the researcher and participants were
      conducted and interpreted using Reinharz's hermeneutic method. Two themes emerged
      from the participants' experiences and are described as 'being-with' and
      'seeing'. 'Being-with' focused on the desire of the participants to 'be-with'
      their relatives, in a physical and emotional sense. The theme 'seeing'
      highlighted the importance of actually seeing the patient. Ontological concepts
      relating to the themes are described with reference to Taylor's concept of being
      human.

PMID- 8568079
TI  - Household family structure and children's aggressive behavior: a longitudinal
      study of urban elementary school children.
AB  - The relationship between contemporary household family structures at fourth-grade
      and sixth-grade parent- and teacher-rated aggression was examined in an
      epidemiologically defined population of urban school children. The relationship
      between family structure and aggression varied by child gender and by parent and
      teacher ratings in the home and school, respectively. After taking into account
      family income, urban area, and fourth-grade aggressive behavior, boys in both
      mother-father and mother-male partner families were significantly less likely
      than boys in mother-alone families to be rated as aggressive by teachers. No
      significant relations between family structure and teacher- or parent-rated
      aggression were found for girls.

PMID- 8568078
TI  - No confirmation of Geschwind's hypothesis of associations between reading
      disability, immune disorders, and motor preference in ADHD.
AB  - Geschwind and colleagues have proposed an association among reading disability,
      immune disorder, and motor preference. Although reading disability commonly
      overlaps with attention deficit hyperactivity disorder (ADHD), ADHD has not been
      previously examined in studies evaluating Geschwind's hypothesis. In this paper
      we evaluate whether ADHD is associated with either asthma or left motor
      preference and whether asthma and left motor preference are associated with each
      other. Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (n = 140) and
      normal controls (n = 120). Information on reading disability, asthma, and motor
      preference was obtained in a standardized manner blind to the proband's clinical
      status. Neither ADHD nor reading disability was associated with either asthma or
      left motor preference nor was asthma and left motor preference associated with
      one another. Our results are not consistent with Geschwind's hypothesis linking
      reading disability, immune disorder, and left motor preference.

PMID- 8568080
TI  - Subgroups of autistic children based on social behavior display distinct patterns
      of brain activity.
AB  - Two questions were addressed in the present study: (1) Do autistic and normally
      developing children exhibit regionally specific differences in
      electroencephalographic (EEG) activity? (2) Do subgroups of autistic children
      classified according to Wing and Gould's (1979) system which emphasizes degree of
      social impairment exhibit distinct patterns of EEG activity? Twenty-eight
      children with autism (5 to 18 years of age) and two groups of normally developing
      children (one matched on chronological age and the other on receptive language
      level) participated. EEG was recorded from left and right frontal, temporal, and
      parietal regions during an alert baseline condition. Compared to normally
      developing children, autistic children exhibited reduced EEG power in the frontal
      and temporal regions, but not in the parietal region. Differences were more
      prominent in the left than the right hemisphere. Furthermore, subgroups of
      autistic children based on Wing and Gould's system displayed distinct patterns of
      brain activity. Compared to autistic children classified as "active-but-odd,"
      "passive" autistic children displayed reduced alpha EEG power in the frontal
      region.

PMID- 8568081
TI  - The effect of child negative affect on maternal discipline behavior.
AB  - The effect of children's negative affect on maternal discipline behavior was
      evaluated in a sample of 39 children (19 to 41 months old) and their mothers.
      Mothers were randomly assigned to view a videotape that contained either a high
      level of child negative affect (NA) or no negative affect (NNA). After viewing
      the videotape, mothers were observed interacting with their own children in three
      tasks designed to elicit child misbehavior. Mothers in the NA condition displayed
      significantly greater overreactivity to child misbehavior; no significant
      difference in laxness was observed between the two groups of mothers. Children of
      mothers in the NA condition tended to display more misbehavior during the last
      two tasks of the interaction. Maternal negative affect received mixed support as
      one possible mediator of this effect.

PMID- 8568082
TI  - Depression and attributions in children and adolescents: a meta-analytic review.
AB  - This article presents a meta-analytic review of the association between
      attributional styles and depressive symptoms in children and adolescents. In 28
      studies involving 7500 subjects, the correlations were consistent with those
      predicted by the reformulated learned helplessness model of depression. For
      negative outcomes, attributions along the internal, stable, and global dimensions
      were associated positively with depression. Conversely, higher levels of
      depressive symptoms were related to more external, unstable, and specific
      attributions for positive events. Additionally, overall composite maladaptive
      attributional patterns for positive and negative events were correlated with
      higher levels of depressive symptoms in youth. Effect sizes for these
      associations ranged from moderate to large (Cohen, 1977). Findings from the
      significance tests of the combined results support the theory. A large number of
      unretrieved studies revealing null effects would be needed to invalidate these
      findings.

PMID- 8568083
TI  - The stability of inhibited/uninhibited temperament from ages 3 to 11 years in
      Mauritian children.
AB  - Stability of inhibited/uninhibited temperament was assessed using 1,795 Mauritian
      children tested at ages 3, 8, and 11 years. Children were divided into
      uninhibited, middle, and inhibited groups at each age based on social behavior.
      Results indicated that, relative to uninhibited children (1) those inhibited at
      age 3 obtained larger inhibition scores at age 8 (p < .0001), (2) those inhibited
      at age 8 obtained larger inhibition scores at age 11 (p < .002), and (3) those
      remaining inhibited from ages 3 to 8 obtained larger inhibition scores at age 11
      (p < .002). Relative to children who changed classification from ages 3 to 8,
      those remaining inhibited obtained larger inhibition scores (p < .05) and those
      remaining uninhibited obtained smaller inhibition scores (p < .015) at age 11.
      Inhibition scores tended to be higher in females by age 11. Results remained
      regardless of ethnicity. The results provide some support that
      inhibited/uninhibited temperament remains stable from ages 3 to 8 and may
      continue to age 11. The results suggest cross-cultural generalizability of these
      findings with implications regarding the development of anxiety disorders in the
      Mauritian population.

PMID- 8568084
TI  - Behavioral and emotional problems among Chinese and American children: parent and
      teacher reports for ages 6 to 13.
AB  - This study compared behavioral and emotional problems reported by parents and
      teachers in Chinese urban and rural samples and demographically similar American
      samples. Parents of 469 6-to-13-year-old children of each nationality completed
      the Child Behavior Checklist (CBCL). Teachers completed the Teacher's Report Form
      (TRF). Cross-cultural differences were generally modest in magnitude. Chinese
      children scored higher on TRF Delinquent Behavior and Anxious/Depressed
      syndromes, and on Internalizing. American children scored higher on CBCL
      Aggressive Behavior and TRF Attention Problems syndromes. Boys exhibited more
      externalizing behaviors across both cultures. The mean correlation between parent
      and teacher ratings was .36 in the Chinese sample and .29 in the American sample,
      a nonsignificant difference. Findings indicate considerable similarity between
      problems reported for children in very different societies.

PMID- 8568085
TI  - The Diagnostic Interview Schedule for Children (PC-DISC v.3.0): parents and
      adolescents suggest reasons for expecting discrepant answers.
AB  - To identify reasons for discrepancies between parent and child reports of
      child/adolescents's psychiatric symptoms, parents and adolescents (51 pairs) were
      asked to guess what the other would answer to questions from the PC-DISC about
      the adolescent's psychiatric symptoms, and to explain why they expected
      disagreement when the answer they provided for the other was different from their
      own. Adolescents' explanations for expecting (1) parental denial of symptoms the
      adolescent reported were: the parent was unaware of, forgot about, assumed the
      adolescent could not have, or trivialized the symptom; and (2) parental report of
      symptoms the adolescent denied were: the parent misread or exaggerated the
      adolescent's symptom, had too high expectations for the adolescent's behavior,
      put a negative label on or did not trust the adolescent. Parents' reasons for
      expecting their children to (1) deny symptoms the parents reported were: the
      adolescent did not remember how s/he felt, lied, did not recognize or minimized
      the importance or frequency of the symptom; and (2) report symptoms the parents
      denied were: the adolescent lied, exaggerated the importance of or interpreted
      the symptom differently.

PMID- 8568086
TI  - Restoration of pediatric posterior teeth.
AB  - Four categories of materials are popular for restoration of slightly to
      moderately carious pediatric primary teeth: amalgam, composite resin, glass
      ionomer and resin-modified glass ionomer. Practitioners looking for a material to
      replace dental amalgam for restoration of pediatric Class II areas will find that
      the most promising and growing technique is using resin-modified glass ionomer.

PMID- 8568087
TI  - A review of dental HMO expenses: where do the dental premium dollars really go?
AB  - The savings and profits that managed care programs have realized in medical care
      have prodded managed care companies to look at dentistry for similar results. In
      this article, the authors evaluate the impact of various dental managed care
      plans by examining how they allocate premium dollars. Dentists and purchasers
      need this information to assure themselves that the plans allocate adequate
      dollars for the provision of care and that the premium dollars paid are used
      effectively and efficiently.

PMID- 8568088
TI  - Gold Hill revisited.

PMID- 8568089
TI  - What dentists need to know about employment law.

PMID- 8568090
TI  - 'The flu zone'.

PMID- 8568091
TI  - Dental radiographs.

PMID- 8568092
TI  - A letter to Dr. Ten Pas.

PMID- 8568093
TI  - Sialorrhea.

PMID- 8568094
TI  - Sedation--guidelines and controls.

PMID- 8568095
TI  - A plea for clarification and consistency.

PMID- 8568096
TI  - Nerve damage and nerve blocks.

PMID- 8568097
TI  - 1995: A year of achievement for the ADA.

PMID- 8568098
TI  - Sinus-lift graft: using the maxillary sinuses to support implants.
AB  - Often, the posterior region of the maxilla lacks the alveolar bone necessary to
      maintain an implant-supported prosthesis. The authors outline a procedure to
      augment the maxillary ridge using a composite alloplastic bone graft. The
      procedure also enables the practitioner to place implants at the time of the
      graft, reducing the surgical and healing time for the patient. Within six to 12
      months of the bone graft, the patient can wear a fixed, implant-supported
      prosthesis. The authors report that patients who have been treated with this
      procedure have maintained stable implant prostheses for over five years.

PMID- 8568099
TI  - The edentulous predicament. I: A prospective study of the effectiveness of
      implant-supported fixed prostheses.
AB  - This prospective longitudinal study follows the treatment of 50 completely
      edentulous patients who could not successfully wear their complete dentures.
      After an initial phase of treatment in which the prostheses of all of the
      patients were optimized, the prosthodontists conducting the study prescribed
      osseointegrated implant-supported fixed prostheses for 45 patients and an implant
      supported overdenture for one patient. Eventually, three of the remaining four
      patients were treated with implant-supported overdentures. This article details
      the results of treatment for all 50 patients over a period of 11 to 15.5 years.

PMID- 8568100
TI  - The edentulous predicament. II: The longitudinal effectiveness of implant
      supported overdentures.
AB  - Fifty consecutive completely edentulous patients who were unable to wear their
      complete dentures took part in this prospective longitudinal study. After
      providing initial optimization treatment of patients' existing prostheses,
      prosthodontists conducting the study prescribed osseointegrated implant-supported
      removable overdentures for 45 of the 50 patients. The remaining five underwent
      ongoing attempts at optimizing their complete dentures. This article details the
      results of treatment for the 50 patients over a period of three to 13 years.

PMID- 8568101
TI  - Evaluating the antagonistic wear of restorative materials when placed against
      human enamel.
AB  - Several clinical and laboratory studies have reported data on the nature of tooth
      wear against restorative materials (that is, amalgam, gold, glass ceramic and
      various composite resin systems). Several antagonistic substrates are known to
      cause various in vitro wear rates when placed in opposition to enamel. In this
      study, the authors evaluated 10 commercially available posterior composite resin
      systems and a gold alloy control. The findings showed that posterior composite
      resins containing zirconium silicate or quartz fillers caused greater
      antagonistic enamel wear than did microfilled or barium silicate-filled composite
      resins.

PMID- 8568102
TI  - Latex hypersensitivity: its prevalence among dental professionals.
AB  - Reports of hypersensitivity to latex are growing among oral health care workers,
      who have a high degree of exposure to latex products. The authors undertook a
      study to determine the prevalence of latex hypersensitivity among oral health
      care workers in a hospital dental practice. Among the 34 people who participated
      in the study, 12 percent had positive results in a skin prick test for latex.
      This suggests that the true prevalence rate of immediate hypersensitivity to
      latex in this group of oral health care workers is similar to that in other
      health care workers who use latex gloves frequently.

PMID- 8568103
TI  - Denture adhesives: changing attitudes.
AB  - Since people began using denture adhesives more than 200 years ago, dentists have
      been slow to acknowledge their place in prosthetic dentistry. The author
      maintains that if properly used, denture adhesives can be an asset to the
      dentist's armamentarium. This article reviews much of the recent research on
      adhesives and outlines the conditions under which they should be used.

PMID- 8568104
TI  - Angina: an update for dentistry.
AB  - Advances in medicine have dramatically altered the diagnosis and treatment of
      angina and the prognosis for patients with this condition. The authors review
      current medical practices and make recommendations for the dental management of
      patients.

PMID- 8568105
TI  - The challenge: motivating women to increase calcium intake from dairy foods.

PMID- 8568106
TI  - Low-protein diets in the treatment of chronic renal failure.
AB  - Dietary protein restriction is an established method of preventing the symptoms
      of uremia but three questions should be asked before beginning this type of
      therapy: Will the diet maintain adequate nutrition? Can compliance be monitored?
      Will the low-protein diet prevent uremic symptoms and change the course of the
      disease? There are positive answers to these questions. Recently it has been
      shown that the metabolic acidosis associated with kidney failure causes
      catabolism by increasing the degradation of muscle protein and of essential amino
      acids. The mechanism for these responses includes increased mRNAs encoding
      enzymes involved in catabolic pathways. Activation of these pathways would impair
      the ability of patients to respond to a low-protein diet because the ability to
      reduce the oxidation of essential amino acids and degradation of protein would be
      limited.

PMID- 8568107
TI  - Asthma and oxidant stress: nutritional, environmental, and genetic risk factors.
AB  - A considerable body of evidence suggests that oxidant stress results in
      inflammation and tissue damage in the respiratory system, and later in immune
      damage, and that individuals with lowered cellular reducing capacity are at
      increased risk to develop asthma. Reducing capacity in the erythrocyte is
      generated through the pentose phosphate pathway and this pathway also generates a
      major portion of the reducing capacity in all cells of the body. Therefore,
      dietary, environmental, and genetic factors which diminish cellular reducing
      capacity will increase tissue vulnerability to oxidant stress and are likely to
      increase asthma risk. Dietary selenium deficiency lowers red cell glutathione
      peroxidase activity and is associated with an increased risk for asthma, and low
      dietary intakes of vitamins C and E also appear to increase asthma risk. High
      body iron stores increase free radical production and may also elevate asthma
      risk. Environmental lead exposure depresses the activities of a several enzyme
      systems that influence cellular reducing capacity (glucose-6-phosphate
      dehydrogenase, NAD synthetase, glutathione peroxidase, superoxide dismutase,
      catalase) and consequently may increase asthma risk. Genetically-determined low
      activity of glucose-6-phosphate dehydrogenase lowers cellular reducing capacity
      and may also heighten asthma risk. Simple dietary and environmental interventions
      may significantly reduce oxidant stress and prevent or minimize the development
      of asthmatic symptoms and should prove to be a cost effective approach to asthma
      management in addition to current pharmacological strategies.

PMID- 8568108
TI  - Fish oil, lipid peroxidation and mammary tumor growth.
AB  - There is evidence that the level and especially the type of dietary fat can be an
      important determinant of mammary tumor development and growth. Diets containing
      high levels of fish oil have been shown to inhibit or suppress mammary tumor
      growth. Various mechanisms have been proposed to explain this modulatory activity
      of dietary fish oil or fats in general on tumor growth; of special interest is
      lipid peroxidation. The oxidation of long chain polyunsaturated fatty acids
      present in fish oil, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA) can produce an array of secondary products of lipid oxidation that may
      possess a cytostatic or cytolytic capacity.

PMID- 8568109
TI  - Factors influencing dairy calcium intake in women.
AB  - OBJECTIVES: Most national dietary studies have reported inadequate calcium (Ca)
      intake by women, indicating that marketing and educational efforts have not
      effected dietary behavior changes. The purpose of this study was to identify
      knowledge, attitudes, and behaviors which influence dairy Ca intake. METHODS: A
      questionnaire was developed to accomplish these objectives, and piloted for
      clarity and content validity. Dietary Ca intake was assessed using a food
      frequency questionnaire. After revisions, women were sampled from four sources: a
      health spa, elderhostel classes, through a Cooperative Extension Service program,
      and from the Illinois Older Women's League. The response rate was 66.5%. RESULTS:
      Mean total reported Ca intake (n = 351) was 591 +/- 355 mg/day. Over 40% of the
      women reported Ca intakes below 60% of the RDA and could therefore be considered
      to have deficient intake. Unfortunately, 27.1% of these with deficient intake
      believed they were meeting the Ca RDA. Significant differences (p < or = 0.01)
      were found in attitudes and beliefs about dairy Ca when comparing women whose
      intake was below 60% of the RDA with those whose intake was above 60%. The most
      commonly mentioned beliefs of the entire sample concerned cholesterol (16.5%),
      high calories (13.7%) and gastrointestinal discomfort (12.8%). CONCLUSIONS: These
      findings suggest an important discrepancy between perceived and actual Ca intake
      which could influence receptiveness to education. Non-dairy Ca rich food sources
      need to be clarified as does the caloric and cholesterol content of dairy foods.

PMID- 8568110
TI  - Reduced non-oxidative glucose utilization in cancer patients is associated with a
      low triiodothyronine concentration.
AB  - OBJECTIVE: Approximately 70% of all cancer patients have elevations in hepatic
      glucose production and/or reductions in glucose utilization. To identify an
      explanation for insulin resistance, we measured fasting hepatic glucose
      production (HGP), leucine appearance (Leu Ra), leucine oxidation (LO), glucose
      oxidation (GO) and non-oxidative glucose utilization at baseline and after
      identical insulin infusion rates (2 pmol/kg/minute, 7 pmol/kg/minute, and 70
      pmol/kg/minute) in eight head and neck cancer patients and eight weight-matched
      disease-free volunteers. METHODS: A step increase in insulin administration
      during a euglycemic clamp protocol was used to measure insulin effects on glucose
      and leucine metabolism. HGP and Leu Ra were determined by performing a primed,
      continuous 10-hour intravenous infusion of 6-3H glucose and 1-14C leucine.
      Baseline insulin, thyroid, TNF, and counter-regulatory hormonal measurements,
      HGP, GO and Leu Ra were obtained between hours 3 and 4. An insulin infusion was
      started at hour 4 and increased every 2 hours for 6 hours. Glucose appearance,
      Leu Ra, GO, LO and insulin concentrations were determined at the end of each 2
      hour interval. RESULTS: Fasting HGP, GO, fat oxidation and Leu Ra were similar
      between the two groups. Insulin administration in cancer patients and normal
      volunteers had a similar effect on LO and Leu Ra. The insulin concentration
      required to stimulate half maximal glucose utilization in cancer patients was
      significantly increased by 58% (470 +/- 82 pM vs. 741 +/- 124 pM; p < or = 0.05).
      Non-oxidative glucose utilization was reduced in the cancer patients at both
      lower doses of insulin infusion (6.4 +/- 2.1 mumol/kg/minute vs. 0.1 +/- 1.6
      mumol/kg/minute p < or = 0.05; and 23.7 +/- 1.3 mumol/kg/minute vs. 15.1 +/- 2.0
      mumol/kg/minute p < 0.01). Triiodothyronine (T3) was directly correlated in the
      cancer patients with non-oxidative glucose utilization at the two physiological
      insulin concentrations (r = 0.673, p < 0.05 and r = 0.731, p < 0.01) and the
      supraphysiological insulin concentration (r = 0.791, p < 0.01). The insulin
      sensitivity index from the euglycemic clamp study was significantly reduced in
      the cancer patients (4.7 +/- 0.7 vs. 2.4 +/- 0.1 (dl/min)/(microU/ml); p < 0.05).
      CONCLUSIONS: In summary, head and neck cancer patients have an abnormal reduction
      in non-oxidative glucose utilization which occurs before abnormalities in HGP,
      GO, or Leu Ra [corrected]. One explanation for the reduced glucose utilization
      may be the influence of a reduced T3 concentration on non-oxidative glucose
      metabolism but further work is needed to confirm these preliminary observations.

PMID- 8568111
TI  - Zinc intake and sources in the US adult population: 1976-1980.
AB  - OBJECTIVE: To determine levels of intake and food sources of zinc in 1976-80 in
      US adults between the ages of 19 and 74. METHODS: Dietary data from 24-hour
      recalls collected in the Second National Health and Nutrition Examination Survey
      were analyzed. Levels of zinc intake were compared between demographic subgroups
      using analysis of variance. The contribution of individual foods to overall zinc
      consumed was also estimated. RESULTS: Mean daily intakes (+/- SEM) were 15.5 mg
      +/- 0.4 and 9.8 mg +/- 0.2 in white men and women, respectively. Mean daily
      intake estimates in black men and women (12.3 mg +/- 0.8 and 7.8 mg +/- 0.3,
      respectively) were significantly lower. Lower intakes were observed in women
      versus men, in older (65 to 74 years) versus younger (19 to 34 years) age groups,
      and among people with lower versus higher education and income levels. Lower zinc
      intakes in women and older persons could be mainly attributed to lower overall
      energy intake compared with gender and age counterparts. However, lower intakes
      in blacks and persons with lower education or income levels were not explained by
      differences in energy intake and may be attributed to differences in food
      selections. Meat and milk products contributed the majority of zinc in recalled
      diets, accounting for 56 and 60% of total zinc intake in blacks and whites,
      respectively. CONCLUSIONS: Levels and sources of zinc intake in 1976-80 were
      higher than in more recent national surveys, suggesting that zinc intakes may be
      declining. Population groups more likely to have lower intakes were women, older
      adults, blacks, and those with lower levels of education and higher poverty
      levels.

PMID- 8568112
TI  - Evening eating and its relation to self-reported body weight and nutrient intake
      in women, CSFII 1985-86.
AB  - OBJECTIVE: We investigated the association of extent of daily energy intake from
      evening food intake with self-reported body weight and nutrient intake. DESIGN:
      Using data from the 1985-86 CSFII, we estimated the proportion of daily energy
      from foods/beverages reportedly consumed after 5 p.m. on 4 non-consecutive days
      by 1802 women, aged 19-50 years. RESULTS: The mean +/- SE of 4-day average energy
      from evening food intake was 46 +/- 0.4%. Body mass index was not associated with
      percent energy from evening food intake in unadjusted or multiple-covariate
      adjusted regression analyses. In multiple-covariate-adjusted regression models,
      percent energy from fat, protein, and grams of alcohol reported were positively
      associated with percent energy from evening food intake (p < 0.05); while percent
      energy from carbohydrate, and percent RDA of vitamins C, B-6, and folate were
      inversely associated with evening eating. CONCLUSIONS: The results do not support
      the hypothesis regarding the association of relative weight with percent energy
      from evening food intake. However, statistically significant differences in
      intake of some nutrients in relation to extent of evening food intake were noted.

PMID- 8568113
TI  - Hypochlorhydria from short-term omeprazole treatment does not inhibit intestinal
      absorption of calcium, phosphorus, magnesium or zinc from food in humans.
AB  - OBJECTIVE: Low gastric pH is generally believed to be an important factor in
      intestinal mineral absorption. Thus, hypochlorhydria could be an important risk
      factor for mineral malabsorption and the development of marginal mineral status.
      We studied whether the hypochlorhydria associated with treatment with the anti
      ulcer medication omeprazole, a potent gastric proton pump inhibition, would
      affect intestinal calcium, phosphorus, magnesium, or zinc absorption from food.
      METHODS: Thirteen normal, healthy adults were assigned to either a control group
      (n = 5) receiving no drug treatment or an omeprazole treatment group (n = 8) to
      produce increased gastric pH. Omeprazole treatment of normal volunteers resulted
      in a significant change in postprandial gastric pH (pH 6.4 +/- 0.3 vs. 3.6 +/-
      0.5 in control subjects, p < 0.01) and baseline fasting pH (pH 5.8 +/- 0.5 vs. pH
      1.8 +/- 0.3 in controls, p < 0.01) after an overnight fast. Net mineral
      absorption from a standard test meal was measured using a whole gut lavage
      technique. Mineral absorption was measured twice in each subject, once with 120
      mL of 0.1 mol/liter hydrochloric acid and a second time with 120 mL of distilled
      water alone. RESULTS: We found that despite marked changes in gastric pH due to
      drug treatment or administration of exogenous HCl, no change in the intestinal
      absorption of calcium, phosphorus, magnesium or zinc from a standard test meal
      was evident. CONCLUSIONS: These findings suggest that changing the gastric pH
      alone does not modify the net intestinal absorption of several minerals from
      food. Therefore, it is unlikely that moderate hypochlorhydria resulting from
      short-term omeprazole treatment substantially increases the risk for developing
      calcium, phosphorus, magnesium, or zinc deficiencies due to mineral
      malabsorption.

PMID- 8568114
TI  - Randomized crossover study of 40% vs. 55% carbohydrate weight loss strategies in
      women with previous gestational diabetes mellitus and non-diabetic women of 130
      200% ideal body weight.
AB  - OBJECTIVE: The optimum diet composition for weight loss in obese women with or
      without previous gestational diabetes mellitus remains to be determined. Weight
      loss may be especially important for the latter group in terms of preventing
      future gestational as well as non-insulin dependent diabetes mellitus. We studied
      40% vs. 55% carbohydrate calorically restricted diets to compare weight loss and
      metabolic response. METHODS: We performed a prospective, 12-week, blinded,
      randomized crossover study of 25 obese women; 13 of whom had previous gestational
      diabetes. Each woman was allocated to a treatment regimen for 6 weeks and then
      "crossed over" to the alternative regimen for an additional 6 weeks. Calories
      were provided in the form of nutritional supplement bars except for the evening
      meal that comprised 1/3 of the caloric needs. All subjects were seen and weighed
      weekly. Metabolic variables including glucose tolerance, glycated proteins,
      lipids, and percent body fat were measured at the beginning, crossover, and end
      of the study. RESULTS: Women with previous gestational diabetes mellitus were
      comparable to obese women without a history of previous gestational diabetes
      except that the former had higher maximum levels of glucose on a glucose
      tolerance test and higher fasting insulin levels consistent with greater insulin
      resistance. Weight loss was comparable for all groups during the first 6 weeks
      but attenuated in all groups during the second 6 weeks of the trial regardless of
      diabetes history or treatment group allocation. Women with or without a previous
      history of gestational diabetes had higher triglycerides while on a 55%
      carbohydrate diet than while on a 40% carbohydrate diet. CONCLUSIONS: A weight
      loss regimen consisting of 40% carbohydrate results in lower triglyceride levels
      than those achieved with a 55% carbohydrate content diet in obese women. Thus,
      the hypocaloric diet with the higher fat content produced the more favorable
      lipid profile in all obese women.

PMID- 8568115
TI  - Maternal-fetal transfer of ionized serum magnesium during the stress of labor and
      delivery: a human study.
AB  - OBJECTIVE: The purpose of this study was to compare levels and fractions of
      ionized magnesium in maternal venous serum with those in umbilical venous and
      arterial serum and to determine whether the maternal levels and fractions change
      during the stress of labor. METHODS: Utilizing an ion-selective electrode, we
      determined levels and fractions of ionized magnesium (IMg2+) and levels of
      ionized calcium (ICa2+) in the maternal venous serum (MVS) of 12 parturients on
      admission and at the end of labor, as well as in the umbilical venous (UVS) and
      umbilical arterial serum (UAS) at delivery. A paired-sample study design was
      used. RESULTS: Whereas mean levels of ICa2+ did not change significantly (p >
      0.05) during labor, the mean (+/- SE) MVS levels of IMg2+ and total magnesium
      (TMg) fell from 0.50 +/- 0.01 and 0.80 +/- 0.02 mmol/L, respectively, on
      admission to 0.46 +/- 0.01 and 0.68 +/- 0.01 mmol/L (p < 0.01 and p < 0.001,
      respectively) at delivery. The ionized fraction, expressed as a percent
      (IMg2+/TMg x 100), increased from 62.8 +/- 2.1% to 67.8 +/- 1.2% (p < 0.05). In
      the UVS, the mean IMg2+ level (0.52 +/- 0.02 mmol/L) and the mean ionized
      fraction (73.6 +/- 1.7%) were higher than in MVS on admission or at delivery (p <
      0.05 for all comparisons). The mean IMg2+ level in UAS (0.50 +/- 0.02 mmol/L) was
      lower than in UVS (p < 0.05), but higher than in MVS at delivery (p < 0.01).
      Finally, there were significant positive correlations between levels of magnesium
      (Mg) in MVS and in the UAS or UVS. CONCLUSIONS: The observation that UAS levels
      of IMg2+ and TMg were similar to the MVS levels on admission despite the fall in
      maternal levels during labor points to the presence of homeostatic mechanisms in
      the fetus and placenta. It is possible that the presence of a higher fraction of
      unbound, free magnesium in UVS enhances magnesium transport to the fetus and thus
      homeostasis. Finally, we hypothesize that the fall in the levels of the
      biologically active form of Mg during labor may be yet another manifestation of
      the known stress responses to labor.

PMID- 8568116
TI  - Lipid and lipoprotein changes after long-term weight reduction: the influence of
      gender and body fat distribution.
AB  - OBJECTIVES: This study was designed: 1) to evaluate the effect of weight loss on
      body fat distribution, 2) to determine whether indices of body fat distribution
      can be considered as a prognostic indicator for the ability to lose weight and 3)
      to evaluate whether a change of body fat distribution is associated with changes
      in plasma glucose, lipids and lipoproteins in both sexes in order to evaluate a
      gender difference. METHODS: 63 obese subjects (41 women and 22 men) were treated
      on an outpatient basis with an energy-reduced, protein-enriched low calorie diet
      (3150-4200 kJ/day) for a 6-month period. They were divided in different groups
      according to gender and body fat distribution using the waist-to-hip
      circumference ratio. RESULTS: Body fat topography can be altered by dieting, but
      not by more than it increases when a person gains weight. Body fat distribution
      seems to be a significant prognostic indicator for the ability to lose weight in
      women but not in men. Although body weight and the waist-to-hip circumference
      decreased significantly, no relationships were found between percent decrease in
      these parameters and percent changes in plasma glucose, lipids and lipoproteins.
      CONCLUSION: We conclude that an important caloric deficit may lead to a series of
      metabolic improvements but that gender and the type of fat distribution are
      important confounding factors in the prediction of metabolic success.

PMID- 8568117
TI  - Metabolic benefits deriving from chronic vitamin C supplementation in aged non
      insulin dependent diabetics.
AB  - OBJECTIVE: Our study investigated the metabolic benefits deriving from chronic
      pharmacological vitamin C administration in aged non-insulin dependent (Type II)
      diabetic patients. METHODS: Forty type II diabetic patients (age: 72 +/- 0.5
      years) underwent placebo and vitamin C (0.5 g twice daily) administration in
      double-blind, randomized, cross-over fashion. All patients were treated by oral
      hypoglycaemic agents which continued throughout the study. After baseline
      observations, treatment periods lasted 4 months and were separated by a 30-day
      wash-out period. RESULTS: Patients' antropometric data were unchanged throughout
      the study. Chronic vitamin C administration vs placebo was associated with a
      significant decline in fasting plasma free radicals (0.26 +/- 0.06 vs 0.49 +/-
      0.07 p < 0.03) and insulin (90 +/- 4 vs 73 +/- 6 pmol/L p < 0.04), total- (7.3 +/
      0.5 vs 5.8 +/- 0.4 mmol/L p < 0.03), LDL-cholesterol (5.6 +/- 0.6 vs 4.1 +/- 0.3
      mmol/L p < 0.05) and triglycerides (2.58 +/- 0.07 vs 2.08 +/- 0.04 mmol/L p <
      0.04) levels. In 20 patients, chronic vitamin C administration improved whole
      body glucose disposal and nonoxidative glucose metabolism. Percent increase in
      plasma vitamin C levels correlated with the percent decline in plasma LDL
      cholesterol (r = 0.44; p < 0.007) and insulin levels (r = 0.42; p < 0.006).
      Finally percent increase in plasma vitamin C levels was correlated with the
      percent decline in plasma free radicals and increase in GSH levels. CONCLUSIONS:
      Chronic vitamin C administration has beneficial effects upon glucose and lipid
      metabolism in aged non-insulin dependent (type II) diabetic patients.

PMID- 8568118
TI  - Short chain fatty acid absorption from the human distal colon: interactions
      between acetate, propionate and calcium.
AB  - OBJECTIVE: Our purpose was to conduct a preliminary study to see if propionate
      and calcium affected acetate absorption, and acetate and calcium affected
      propionate absorption from the human distal colon. METHODOLOGY: We studied six
      healthy subjects on eight occasions in randomized order after overnight fasts.
      Test solutions (300 ml) were infused into the rectum, retained for 30 minutes,
      and then the infusion fluid was collected for analysis. The infusion solutions
      contained combinations of sodium acetate (56.25 mmol/L), sodium propionate (18.75
      mmol/L) and calcium chloride (50 mmol/L) plus polyethylene glycol (PEG) as an
      unabsorbable marker. RESULTS: The reduction in the acetate:PEG concentration
      ratio over 30 minutes after acetate alone, 4.1 +/- 4.2, was significantly less
      than after acetate plus propionate, 40.2 +/- 11.9, and acetate plus calcium, 34.0
      +/- 8.9 (p < 0.05). However, the change in acetate:PEG ratio when acetate,
      propionate and calcium were all infused together, 13.2 +/- 4.6, was no different
      from acetate alone. The reduction in the propionate:PEG concentration ratio after
      propionate alone was 15.7 +/- 3.3, and this was not significantly affected by
      adding acetate and calcium either alone or together. CONCLUSIONS: We conclude
      that the absorption of acetate in the rectum and distal colon of humans may be
      influenced by the presence of calcium and propionate. More detailed kinetic
      studies are required to confirm these results and characterize the transport
      mechanisms involved.

PMID- 8568119
TI  - Dietary ferric vs. ferrous iron in copper-deficient rats fed fructose-based
      diets.
AB  - OBJECTIVE: This preliminary study was undertaken to determine whether the valence
      state of dietary iron affects signs associated with copper deficiency in rats fed
      fructose. METHODS: Rats were fed either copper-deficient or adequate diets
      containing 62% fructose as the sole dietary carbohydrate for 5 weeks. The mineral
      mixture contained equal concentration of either ferric or ferrous iron. RESULTS:
      Copper deficiency resulted in growth retardation, anemia, heart hypertrophy but
      pancreatic atrophy. The consumption of ferrous iron resulted in increased
      hematocrit and pancreas size. The combination of ferrous iron with copper
      deficiency reduced heart size. CONCLUSIONS: Copper deficiency had a major impact
      on each parameter measured. Although the valence state of iron did not protect
      the rats against the pathological consequence of copper deficiency it did have
      some positive effects. It may be that ferrous iron is a more available form than
      ferric iron.

PMID- 8568120
TI  - Recent studies regarding the role of childhood nutrition in the prevention of
      atherosclerosis.

PMID- 8568121
TI  - Decreased adrenal sex steroid levels in the absence of glucocorticoid suppression
      in postmenopausal asthmatic women.
AB  - BACKGROUND AND AIM: Reduction of serum sex steroid levels has been reported to
      occur after the administration of beta-adrenergic medication. In that beta
      adrenergic blockade is a central pathophysiologic feature of asthma, this study
      was done to explore the possibility of hormonal alteration in asthma. METHODS:
      Sex steroids obtained from 22 postmenopausal asthmatic and 22 age-matched,
      postmenopausal, nonasthmatic women were assayed. No subject had received
      estrogens, progestins, or oral corticosteroids for 120 days before the study.
      RESULTS: Mean dehydroepiandrosterone sulfate (DHEAS; p < 0.002),
      dehydroepiandrosterone (DHEA; p < 0.03), estradiol (p < 0.02), and estrone (p <
      0.02) levels were lower in asthmatic patients compared with nonasthmatic
      subjects. Results could not be accounted for by current medication. Patients with
      asthma demonstrated no decrease in 17-hydroxyprogesterone or cortisol compared
      with nonasthmatic subjects, limiting findings to the delta 5, and not the delta
      4, steroidogenic pathway. In a second phase of the study, DHEAS was measured
      before and after 3 days of oral beta-agonist stimulation in eight postmenopausal
      asthmatic women. Serum DHEAS concentration increased in eight of eight subjects,
      from a mean of 28.6 +/- 19.9 micrograms/dl (mean +/- SD) to 40.7 +/- 24.8
      micrograms/dl (p = 0.002). Serum cortisol concentration was unchanged.
      CONCLUSION: The results indicate that postmenopausal asthmatic women have lower
      serum levels of adrenally derived sex steroids than their nonasthmatic peers and
      that this anomaly may be ameliorated by adrenergic stimulation.

PMID- 8568122
TI  - Chemokines in seasonal allergic rhinitis.
AB  - Monocyte chemotactic and activating factor/monocyte chemoattractant protein-1
      (MCAF/MCP-1), RANTES, and macrophage inflammatory protein (MIP)-1 alpha are
      chemokines known to activate basophils (MCAF/RANTES) and eosinophils (RANTES/MIP
      1 alpha). IL-8 inhibits MCAF-induced histamine release from basophils. We
      questioned whether a relationship exists between the levels of these chemokines
      and various inflammatory mediators released from mast cells, eosinophils, and
      basophils as assessed in nasal secretions obtained from patients during the
      allergy season and out of season. Samples were assessed for MCAF/MCP-1, RANTES,
      MIP-1 alpha, IL-8, histamine, tryptase and eosinophil cationic protein (ECP) in
      three subject groups: subjects with allergic rhinitis (n = 18), atopic subjects
      without rhinitis (n = 9), and healthy individuals (n = 6). Statistically
      significant differences were apparent only in the subjects with symptoms as
      follows. MCAF/MCP-1 increased during the season from 336 +/- 47 pg/ml to 829 +/-
      137 pg/ml (p < 0.001), whereas IL-8 decreased from a baseline of 1932 +/- 335
      pg/ml to 1070 +/- 202 pg/ml (p < 0.028). The ratio of IL-8 to MCAF/MCP-1
      decreased during the symptomatic season from the baseline of 6.66 +/- 1.06 seen
      during winter to 1.3 +/- 0.22 during ragweed season (p < 0.001). Histamine
      increased from 6.3 +/- 1.5 to 89 +/- 15.5 ng/ml (p < 0.001), ECP increased from
      20.6 +/- 6.4 to 237.1 +/- 50.2 ng/ml (p < 0.001), and tryptase increased from
      2.34 +/- 0.6 to 9.7 +/- 2.3 U/ml (p < 0.001). Most samples did not have
      detectable quantities of MIP-1 alpha or RANTES. We also found a correlation
      between the level of MCAF/MCP-1 and IL-8 and the level of histamine or IL-8 and
      ECP. Our results suggest that the chemokines MCAF/MCP-1 and IL-8 may participate
      in the pathogenesis of allergic rhinitis, contributing to the attraction of the
      proinflammatory cells and mediator release, which might be very important during
      the late phase of the allergic reaction. Furthermore, the ratio of certain
      chemokines, such as MCAF/MCP-1 and IL-8 may reflect the magnitude of the
      reaction, as does the presence of histamine and ECP.

PMID- 8568123
TI  - Short courses of high-dose inhaled budesonide and serum IgG subclass levels in
      healthy volunteers.
AB  - BACKGROUND: The incidence of systemic side effects of inhaled budesonide
      increases at doses exceeding 2000 micrograms/day. OBJECTIVE: This study was
      carried out to investigate whether high-dose inhaled budesonide affects serum IgG
      subclass concentrations in healthy adult volunteers. METHODS: Two groups of 10
      subjects each inhaled 2.4 mg of budesonide per day in a double-blind, crossover
      study of morning (8:00 AM and noon, group A) and diurnal (8:00 AM and 8:00 PM,
      group B) dosing schedules for 4 weeks each, separated by a 2-week washout period.
      The budesonide was inhaled through a pressurized metered-dose inhaler, mounted on
      a 750 ml Nebuhaler (ASTRA Pharmaceuticals, Lund, Sweden). The IgG subclass levels
      were determined at baseline and every 2 weeks until the end of the study period
      (10 weeks). RESULTS: There were no statistically significant changes in the serum
      IgG subclass concentrations over the 10-week study period in group A, group B, or
      groups A and B combined. CONCLUSION: Inhalation of budesonide, 2.4 mg/day,
      through a large-volume spacer for repeated 1-month periods does not influence
      serum IgG subclass concentrations in healthy adults, suggesting that budesonide
      does not cause systemic humoral immunosuppression when given at therapeutic
      doses.

PMID- 8568124
TI  - Double-blind placebo-controlled study of the efficacy of oral terfenadine in the
      treatment of chronic fatigue syndrome.
AB  - BACKGROUND: There is no established treatment for chronic fatigue syndrome (CFS),
      an illness characterized by disabling fatigue exacerbated by physical activity. A
      variety of immunologic abnormalities have been reported, including a high
      incidence of atopy and hypoergy or anergy. OBJECTIVE: Because of anecdotal
      reports and uncontrolled trials showing antihistamine efficacy in CFS, we
      evaluated the clinical efficacy of the antihistamine terfenadine (60 mg twice
      daily) in a placebo-controlled study. METHODS: Thirty patients with CFS were
      enrolled in a 2-month, double-blind, placebo-controlled trial of terfenadine.
      Participants underwent a battery of both immediate- and delayed-type
      hypersensitivity skin tests and completed a self-assessment questionnaire used to
      measure severity of symptoms, physical and social functioning, health
      perceptions, and mental health before each of six biweekly visits. RESULTS:
      Twenty-eight patients completed the trial. History of atopy and positive
      immediate skin test results were prevalent, 73% and 53%, respectively. No
      evidence for hypoergy or anergy after delayed-type hypersensitivity skin testing
      was found. No therapeutic benefit from terfenadine could be detected in terms of
      symptom amelioration, improved physical or social functioning, health
      perceptions, or mental health. A high incidence of atopy in patients with CFS was
      confirmed. CONCLUSION: Although this trial involved a small number of patients,
      the results suggest that terfenadine is unlikely to be of clinical benefit in
      treating CFS symptoms.

PMID- 8568125
TI  - Desensitization treatment for anaphylactoid reactions to desferrioxamine in a
      pediatric patient with thalassemia.

PMID- 8568126
TI  - Elephantiasis nostras: a case report.

PMID- 8568127
TI  - Baker's asthma caused by Saccharomyces cerevisiae in dry powder form.

PMID- 8568128
TI  - Increased plasma IgE levels in patients with sepsis after traumatic injury.

PMID- 8568129
TI  - Anaphylaxis to trimethoprim.

PMID- 8568130
TI  - Corticosteroids and IgE. Dutch CNSLD Study Group.

PMID- 8568131
TI  - Immunotherapy in young children.

PMID- 8568132
TI  - Splenomegaly in idiopathic hypereosinophilic syndrome.

PMID- 8568133
TI  - The relationship between RAST and skin test results in patients with asthma or
      rhinitis: a quantitative study with purified major allergens.
AB  - BACKGROUND: Study of the relationship between skin test results and IgE antibody
      levels is seriously hampered by the use of conventional allergen extracts because
      the precise amount of relevant allergen for each patient is unknown. OBJECTIVE:
      This study was designed to investigate skin reactivity with purified major
      allergens and to assess the relation with serum levels of IgE antibodies and to
      determine which additional factors contribute to the skin test result. METHODS:
      We used five purified major allergens (Der p 1, Der p 2, Fel d 1, Lol p 1, and
      Lol p 5) in skin tests, RASTs, and histamine release tests in 43 multisensitized
      patients with asthma or rhinitis. RESULTS: The differences in biologic activity
      of the five major allergens at a given level of specific IgE are within one order
      of magnitude. A significant residual variation remains in the correlation between
      skin test results and levels of IgE antibodies, which cannot be explained by
      imprecision of both tests (Pearson log skin test vs log specific IgE: r = 0.46
      0.92). With similar levels of specific IgE, the amount of allergen that is
      required for a positive skin test result may differ by as much as a factor of 100
      between patients. The amount of total IgE in serum contributes significantly to
      the skin test result. High values of total IgE are accompanied by a lower skin
      reactivity for allergen. Within individuals, allergens that cause skin test
      results that deviate from the prediction based on IgE antibody level often show a
      similar deviation in the histamine release test. This indicates that the type of
      IgE response (i.e., affinity or epitope recognition pattern) contributes
      significantly to the skin test result. Skin reactivity for histamine does not
      significantly influence the skin reactions expressed as allergen threshold.
      However, increased skin reactions with higher allergen dosages depend on
      histamine reactivity. CONCLUSION: The major allergens tested show similar
      biologic activities. In addition to IgE antibody level, total serum IgE and type
      of IgE antibody response contribute significantly to the skin test threshold for
      allergens. Even in a system with purified allergens, IgE antibody levels and skin
      test results are not interchangeable as an indicator of the degree of allergic
      sensitization.

PMID- 8568134
TI  - Allergic reactions to cyclophosphamide: delayed clinical expression associated
      with positive immediate skin tests to drug metabolites in five patients.
AB  - BACKGROUND: Cyclophosphamide (CP) is one of the relatively few drugs implicated
      in systemic allergic reactions for which the metabolites are well known.
      Formation of CP metabolites is a multistep, time-dependent process (hours) with
      significant interindividual differences. Although allergic reactions to CP have
      been recorded in 17 previous reports, skin testing with CP or its metabolites has
      been included in only five. We now describe five patients receiving monthly
      cycles of intravenous CP whose allergic reactions included clinical features of
      type I hypersensitivity but were atypical in their markedly delayed onset (i.e.,
      8 to 16 hours in patients 1 to 4 and 10 days in patient 5). OBJECTIVE: The
      objective was to investigate these late-developing clinical reactions by skin
      testing with CP and two of its major metabolites. METHODS: The five patients and
      a control group receiving intravenous CP uneventfully were studied by the same
      skin test protocol. RESULTS: The four individuals in the control group were
      unreactive to CP or its metabolites. All five patients with late-onset allergic
      reactions had positive immediate skin test results to CP metabolites but not to
      CP itself. We propose that the allergic reactions in patients 1 to 4 were
      mediated, wholly or in major part, by IgE antibodies reactive with allergens
      derived from time-dependent drug metabolites. The 10-day lag time in patient 5 is
      unexplained. Immunomodulation by the underlying malignancies or by the
      immunosuppressive drugs could have contributed. CONCLUSION: IgE-mediated allergic
      drug reactions may have a delayed onset if the allergen is a time-dependent drug
      metabolite, illustrated in this study by CP.

PMID- 8568135
TI  - Local nasal immunotherapy with extract in powder form is effective and safe in
      grass pollen rhinitis: a double-blind study.
AB  - BACKGROUND: Local nasal immunotherapy has been studied, by means of an extract in
      powder form, in patients with allergic rhinitis caused by grass pollen. METHODS:
      Thirty-two patients allergic to grass were studied for 37 weeks in a double-blind
      controlled trial. Subjects were selected on the basis of a positive history, skin
      test result, RAST finding, and result of intranasal challenge to grass pollen.
      Two 16-patient groups were randomly assigned to active or placebo treatment. The
      treatment lasted 26 weeks (14 for the build-up phase, 12 for the maintenance
      period). RESULTS: No significant differences were observed in nasal symptoms
      during the treatment. During the pollen season the mean weekly symptom and
      medication scores were significantly lower in the treated group, compared with
      the control group, even considering each allergic symptom separately. Moreover,
      only in the treated group was a significant increase of specific nasal threshold
      to grass pollen observed after treatment. CONCLUSIONS: This study indicates that
      local nasal immunotherapy with allergen in powder form can be a suitable
      alternative to the traditional subcutaneous immunotherapy in terms of clinical
      efficacy and safety in grass-allergic rhinitis.

PMID- 8568136
TI  - Successful parenteral desensitization to paclitaxel.
AB  - BACKGROUND: Paclitaxel, a member of a new class of antineoplastic agents called
      the taxanes, has been associated with anaphylactoid reactions. OBJECTIVE: We
      report a case of successful parental desensitization to paclitaxel. METHODS:
      Desensitization was performed with serial 10-fold dilutions (up to 1:100,000) of
      paclitaxel in sufficient volume to administer successive doses of 1, 2, 4, and 8
      ml. Basophil histamine release tests were performed with paclitaxel alone,
      vehicle alone, and paclitaxel and vehicle combined to determine which agent was
      responsible for the anaphylactoid reactions. RESULTS: After parental
      desensitization was performed, the patient was able to tolerate infusion of
      paclitaxel without complications or need for antihistamines or steroids. Basophil
      histamine release occurred only with paclitaxel and not with the vehicle.
      CONCLUSIONS: Successful parenteral desensitization to paclitaxel can be achieved;
      it is paclitaxel, and not its vehicle, that is most likely responsible for
      anaphylactoid reactions in patients undergoing treatment.

PMID- 8568137
TI  - Salbutamol-induced increased airway responsiveness to allergen and reduced
      protection versus methacholine: dose response.
AB  - BACKGROUND: Two adverse effects of inhaled beta 2-agonists are increased airway
      responsiveness to allergen and tolerance to the bronchoprotective effect of beta
      2-agonists versus bronchoconstrictors (e.g., methacholine). OBJECTIVE: We studied
      three doses of inhaled salbutamol, 200, 400, and 800 micrograms/day, to determine
      dose-response curves for these two adverse effects. METHODS: Ten atopic patients
      with mild, stable asthma free of all asthma medications, allergen exposure, and
      respiratory tract infection for at least 4 weeks participated in a double-blind,
      random-order, crossover study. There were four 1-week treatment periods with a 1
      week washout period: placebo, salbutamol 200 micrograms, 400 micrograms and 800
      micrograms per day. After each treatment, we assessed FEV1, bronchodilation 10
      minutes after administration of 200 micrograms of salbutamol, methacholine PC20,
      methacholine dose-shift after administration of 200 micrograms of salbutamol, and
      allergen PC20. RESULTS: There was no significant difference in baseline FEV1,
      bronchodilation, or methacholine PC20. The methacholine dose shift was maximum
      after the placebo (3.4 +/- 0.22 doubling doses) and was significantly greater (p
      < 0.01) than all salbutamol regimens (2.2 to 2.6), which were not significantly
      different from each other (p > 0.05). Allergen PC20 was significantly lower (p <
      0.02) after salbutamol 800 micrograms/day (geometric mean = 288 protein nitrogen
      units [PNU]/ml) than each of the other treatments (447 to 550 PNU/ml), which were
      not significantly different from each other (p > 0.05). CONCLUSION: Significant
      increase in airway responsiveness to allergen occurred only with the largest dose
      of inhaled salbutamol (800 micrograms/d); however, tolerance to the acute
      bronchoprotective effect of salbutamol was observed with all the three salbutamol
      regimens, even 200 micrograms/day. This suggests different mechanisms may be
      operative in producing these two effects.

PMID- 8568138
TI  - Single amino acid substitutions on a Japanese cedar pollen allergen (Cry j 1)
      derived peptide induced alterations in human T cell responses and T cell receptor
      antagonism.
AB  - We generated T cell clones specific to a Japanese cedar pollen allergen (Cry j 1)
      and investigated effects of altered T cell receptor (TCR) ligand on changes of T
      cell responses. One of these Cry j 1-specific T cell clones established from
      patients with Japanese cedar pollinosis, ST1.9, recognized an antigenic peptide
      Cry j 1 p335-346 in the context of HLA-DRA+DRB3*0301 molecules and secreted
      interleukin-4 dominantly, with a smaller amount of interferon-gamma. ST1.9
      represented one of the major T cell clones specific to Cry j 1 in the donor,
      because a short-term cultured polyclonal T cell line specific to Cry j 1
      exhibited the same character as the ST1.9. We synthesized various analog peptides
      derived from Cry j 1 p335-346 with single amino acid substitutions and determined
      key residues for interactions between TCR of ST1.9 and HLA-DR molecules. We also
      analyzed changes in the responses of ST1.9 to Cry j 1 p335-346-derived analog
      peptides. Of interest was that the substitution of 339threonine to valine
      resulted in a significant increase in interferon-gamma production, with no
      remarkable changes either in proliferative response or interleukin-4 production.
      Analog peptides carrying the substitutions of 339threonine to glycine or
      glutamine revealed TCR antagonism, without changes in their binding affinities to
      the DR molecule. Therefore single amino acid substitutions on an allergen peptide
      carrying the T cell epitope may suppress helper-T-dependent class switch pressure
      to IgE in B cells either by inducing increased interferon-gamma production or by
      inhibiting proliferative responses in helper-T cells.

PMID- 8568139
TI  - Food allergy to honey: pollen or bee products? Characterization of allergenic
      proteins in honey by means of immunoblotting.
AB  - OBJECTIVE: To characterize the allergenic components of honey, 23 patients
      allergic to honey were investigated. All displayed allergic symptoms after
      ingestion of honey or honey-containing products, ranging from itching in the oral
      mucosa to severe systemic symptoms to anaphylactic shock. METHODS AND RESULTS:
      Immunoblot analyses of the patients' sera revealed IgE binding to proteins at a
      molecular mass of 54 kd, 60 kd, 72 kd, or to a 30 kd/33 kd double band, or to
      both in sunflower honey extracts. The three bands corresponding to higher
      molecular mass proteins could also be detected in the three other kinds of honey
      (locust tree, European chestnut and forest honey) that were tested and
      represented bee products because IgE binding to these proteins was inhibited by
      extracts of honeybee heads and extracts of isolated bee venom sacs. The 30 kd/33
      kd bands could be identified as sunflower honey-specific. When testing sera from
      patients allergic to bee venom with honey extracts, in seven of 10 cases IgE
      binding to bee-specific components could be observed. CONCLUSION: Both proteins
      derived from secretions of pharyngeal and salivary glands of honeybee heads and
      pollen proteins contained in the honey cause allergic reactions to honey.

PMID- 8568140
TI  - Investigation of the mechanism of alcohol-induced bronchial asthma.
AB  - BACKGROUND: Many Japanese patients with asthma experience episodes or
      exacerbation of asthma after alcohol consumption. This phenomenon is not seen in
      Caucasians and is specific to Asians. This has been thought to be attributable to
      a difference in alcohol metabolism, in particular the metabolism of acetaldehyde,
      between Asians and Caucasians. METHODS: An oral ethanol challenge test, a
      leukocyte histamine release test, and an ELISA for detection of IgE specific to
      acetaldehyde-human serum albumin conjugate were carried out in 42 adults with
      bronchial asthma and nine healthy adults. RESULTS: Fifty-five percent of the
      patients with asthma responded to the ethanol challenge and showed a 20% or
      greater reduction in forced expiratory volume in 1 second. Blood acetaldehyde and
      plasma histamine levels were significantly higher in responders than in
      nonresponders. The leukocyte histamine release test revealed no ethanol-induced
      histamine release. Acetaldehyde, on the other hand, was found to induce histamine
      release in a volume-dependent manner. The histamine release was significantly
      higher in the asthma group (both responders and nonresponders) than in the
      healthy control group. ELISA did not detect any IgE specific to acetaldehyde
      human serum albumin conjugate. CONCLUSION: Alcohol-induced bronchial asthma seems
      to develop as follows. Alcohol elevates blood acetaldehyde levels, which leads to
      degranulation of mast cells (or basophils). The resultant release of chemical
      mediators, such as histamine, induces asthma.

PMID- 8568141
TI  - Prostaglandin E2 control of T cell cytokine production is functionally related to
      the reduced lymphocyte proliferation in atopic dermatitis.
AB  - Past studies of peripheral blood mononuclear cells (PBMC) from patients with
      atopic dermatitis (AD) have demonstrated reduced proliferation. We have studied
      phytohemagglutinin-induced lymphocyte proliferation in the context of interleukin
      4 (IL-4), interferon-gamma (IFN-gamma), and prostaglandin E2 (PGE2) production in
      cultures of PBMC from patients without and with AD. The proliferation index was
      found to correlate proportionally to IFN-gamma production and inversely to T-cell
      IL-4 and monocyte PGE2 production. Assays in parallel cultures showed
      significantly increased PGE2 production by purified AD monocytes. The
      proliferation index in PBMC from persons with AD was significantly reduced
      compared with normal PBMC. This difference was normalized in the presence of
      extrinsic IFN-gamma but exaggerated when IL-4 was added. Increased AD monocyte
      production of inflammatory factors (e.g., PGE2) and cytokines appears to increase
      IL-4 production by Th2 while suppressing IFN-gamma production by Th1. Restoration
      of the normal proliferation of PBMC by the addition of IFN-gamma may represent
      one mechanism for the clinical efficacy of IFN-gamma treatment of AD.

PMID- 8568142
TI  - Combined skin prick and patch testing enhances identification of food allergy in
      infants with atopic dermatitis.
AB  - BACKGROUND: Early recognition of dietary allergies in infants with atopic
      dermatitis is essential for avoidance of unnecessary elimination diets,
      amelioration of the skin disease, and secondary prevention of the development of
      multiple food allergies. Simple and accurate methods of identifying provocative
      foods are urgently needed. METHODS: The usefulness of skin prick and patch tests
      as indicators of cow milk allergy was evaluated in 183 patients ranging in age
      from 2 to 36 months with double-blind, placebo-controlled (n = 118) or open (n =
      65) cow milk challenges. RESULTS: The oral cow milk challenges were interpreted
      as positive in 54% of both challenge types. Positive challenge rapidly elicited
      pruritus, urticaria, and/or exanthema in 49% of cases and delayed-onset
      eczematous lesions in 51%. The skin prick and patch tests gave markedly
      discrepant results; prick tests were positive in 67% of the cases with acute
      onset reactions to milk challenge, whereas patch tests tended to be negative.
      Patch tests were positive in 89% of those with delayed-onset reactions, although
      prick tests were frequently negative. CONCLUSIONS: The observations indicate that
      IgE and T cell-mediated responses to cow milk can be distinguished in atopic
      dermatitis. Parallel skin testing with combined prick and patch tests can
      significantly enhance the accuracy in diagnosis of specific dietary allergies in
      patients with atopic dermatitis.

PMID- 8568144
TI  - Molecular actions of glucocorticoids: an introduction.

PMID- 8568143
TI  - Induction of IgE antibodies with predefined specificity in rhesus monkeys with
      recombinant birch pollen allergens, Bet v 1 and Bet v 2.
AB  - BACKGROUND: Recombinant birch pollen allergens Bet v 1 and Bet v 2 (birch
      profilin) have been characterized in vitro previously. OBJECTIVE: To establish a
      close-to-man model of type I allergy, recombinant birch pollen allergens were
      injected into rhesus monkeys. METHODS: The allergens were expressed in
      Escherichia coli, purified to homogeneity and injected into rhesus monkeys with
      aluminium hydroxide as adjuvans. The development of type I allergy was monitored
      by measurement of specific IgE, in vitro histamine release tests, cellular
      proliferation assays, skin testing, and bronchial provocation tests. RESULTS:
      Immunized rhesus monkeys displayed symptoms of type I allergy comparable to those
      of allergic patients, and cross-reactivity of IgE antibodies with Bet v 1 and Bet
      v 2 homologous allergens was observed. Systemic application of corticosteroids
      during secondary immunizations suppressed specific antibody responses.
      CONCLUSION: Recombinant birch pollen allergens (Bet v 1 and Bet v 2) were
      effective to establish a close-to-man model of natural type I allergy in rhesus
      monkeys, allowing study of specific IgE regulation in vivo.

PMID- 8568145
TI  - Glucocorticosteroid inhibition of cytokine production: relevance to antiallergic
      actions.
AB  - We believe that there are the following four classes of glucocorticoid-sensitive
      cytokines that are involved in cell recruitment: (1) those that activate
      endothelium nonspecifically; (2) those that activate endothelium specifically;
      (3) those that activate, prime, and prolong the survival of eosinophils; and (4)
      those that stimulate movement of cells up into the epithelium. Glucocorticoids
      inhibit the generation of these cytokines and thereby prevent several different
      aspects of inflammation, including the activation and recruitment of inflammatory
      cells (eosinophils, basophils, and lymphocytes) and the release of inflammatory
      mediators. We believe such pleiotropic actions account for the efficacy and
      widespread use of glucocorticoids in the treatment of asthma.

PMID- 8568146
TI  - Remodeling of asthmatic airways by glucocorticosteroids.

PMID- 8568147
TI  - Molecular mechanisms of steroid action in asthma.

PMID- 8568148
TI  - Pharmacodynamics and pharmacokinetics of inhaled glucocorticoids.

PMID- 8568149
TI  - Clinical use of inhaled corticosteroids in asthma.

PMID- 8568150
TI  - The process of interpretation and the moment of change.
AB  - The effectiveness of analytic interpretation is conditioned by a number of
      factors within the patient, within the analyst, and within the analytic
      situation. I will focus on one of these factors, part of the technical activity
      of the analyst that I will call follow-up interpretation, one which omitted, or
      even slighted, sharply diminishes the effectiveness of interpretation.

PMID- 8568151
TI  - When do interpretations make a difference? A partial answer to Fliess's Achensee
      question.
AB  - Interpretations seem to matter most (at least in the case of Mrs. C) when the
      analyst feels included in the patient's thoughts. During hours of this kind
      (Related hours, scoring high on the cooccurrence of first- and second-person
      pronouns such as me/you), the analyst's interpretations are more comprehensive
      and probing; he intervenes earlier and more often within the session; and his
      specific interpretations have a greater effect on the patient's associations, as
      measured by an increased frequency of specific discourse markers. Low-scoring
      hours, with relatively few pronominal references to the analyst, were
      characterized by more superficial interpretations; later and fewer interventions;
      a greater tendency for the analyst to misunderstand the patient's productions;
      and a decreased effect of specific interventions. Special care was taken to
      protect the findings from the dangers of suggestion (the Achensee question).

PMID- 8568152
TI  - Clinical truth and contemporary relativism: meaning and narration in the
      psychoanalytic situation.
AB  - This paper proposes that clinical psychoanalysis requires distinctions for its
      practice that tend to be blurred by a less than careful importation of
      contemporary philosophical concepts. One such distinction is that between
      narration and the event narrated; another, that between meaning seen as
      absolutely relative and meaning understood as hierarchical. The first distinction
      identifies present experience as formed by a narrative strategy arrived at in the
      past. The second distinction allows pathology to be described as arrests or
      limitations in the ability to construe meaning. This perspective has implications
      for a number of current debates, among them those concerning the roles of
      interpretation and reconstruction. A clinical illustration involving the
      reconstruction of a disavowed perception and relying on the aforementioned
      distinctions is presented.

PMID- 8568153
TI  - A classic revisited: clinical and theoretical reflections on Stone's Widening
      scope of indications for psychoanalysis.
AB  - Leo Stone's "The Widening Scope of Indications for Psychoanalysis" has had a
      major influence on the way almost two generations of American psychoanalysts have
      been taught to think about and practice psychoanalysis. Contemporary elaborations
      and extensions of the ideas contained in Stone's paper have, however, been used
      to move us steadily toward a shift in the treatment paradigm that underlies the
      way psychoanalysis is currently being conducted. This contemporary tendency to
      enlarge the scope of the mode of action of psychoanalysis, in order to
      accommodate the wider range of patients being treated today, blurs those aspects
      of psychoanalytic technique that distinguish the unique psychoanalytic
      perspective from the more general psychotherapeutic perspective. Several ideas
      contained in Stone's paper are considered as a basis for clarifying this
      distinction and the technical implications deriving from it. Two clinical
      vignettes are presented to illustrate these issues.

PMID- 8568154
TI  - Transferences of deception.
AB  - Three characteristic transference configurations are identified that frequently
      emerge in the analyses of patients for whom deception and inauthenticity are
      central themes. These configurations are labeled (1) imposturous, (2)
      psychopathic-paranoid, and (3) psychopathic-unreal. Patients who develop these
      transferences have actively split the object world along two distinct axes. The
      first split has occurred along the lines of pleasure and unpleasure. The second
      divides objects along the lines of the experience of reality, with some objects
      felt to be charged with exaggerated, painful meaning, and others felt to be
      devoid of meaning and affect. This split, which arises as a way of managing
      painful object relations, is then woven into fantasy and defense at many
      developmental levels. Material from the analyses of two patients is presented to
      demonstrate the interplay of the three transference configurations, the fantasies
      that underlie them, and the clinical importance of analyzing the second split.

PMID- 8568155
TI  - Psychological-mindedness as a defense.
AB  - Many patients seen today use sophisticated capacities for psychological
      reflection and premature synthesis to ward off knowledge of more primitive
      conflict and islands of unintegration. They show a precocious talent for free
      association, a talent they perversely misuse. Similarly, they enjoy access to a
      rich fantasy life, even as they subtly impoverish it. Effective therapeutic work
      requires that they suffer "traumatization"--experiences of dedifferentiation that
      undermine their considerable capacity to know what they feel and think.
      Structural and process variables interact with content variables in complex and
      ambiguous ways. As a consequence, estimates of the authenticity and "fit" of
      personal and interpersonal experiences and behaviors of both partners in the
      therapeutic encounter become necessarily involved. Such factors may increase the
      possibility of misunderstandings, but also of more authentic and firmly grounded
      understandings. Similar issues are eventually revealed in these patients' early
      lives, where psychological and other formulaic understandings were prematurely
      applied to offset overwhelmedness and other unarticulable experiences; the
      patient's talents for ambiguity, irony, self-soothing, or responsiveness to
      others were, in effect, exploited at the expense of full psychological growth.
      Versions of this clinical presentation may be increasingly common in a new
      generation of analyzable patients. Clinical work with them is facilitated by a
      synthesis of contemporary developmental, structural, and object relations theory.

PMID- 8568156
TI  - The story of a transgression.

PMID- 8568157
TI  - Freud in America. Panel report.

PMID- 8568158
TI  - Enactments of boundary violations. Panel report.

PMID- 8568159
TI  - [Penetrating keratoplasty after graft preservation in organ culture at +37
      degrees centigrade. 1-year results].
AB  - PURPOSE: To evaluate the clinical results of corneal transplantations using organ
      cultured donor corneas. MATERIAL AND METHODS: We retrospectively studied our 50
      first penetrating keratoplasties performed with corneas organ-cultured for 2 to 5
      weeks at +31 degrees C (Inosol medium, Opsia). The average follow-up is 11.6
      months. The main indications for grafting were bullous keratopathy (56%) and
      keratoconus (26%). RESULTS: At 1 year, the graft survival rate was 81%. The
      causes of graft failure were immune rejection (n = 3), non immune secondary
      endothelial decompensation (n = 3) and uncontrolled glaucoma (n = 1). The average
      endothelial density during the second year was 1,349 cell/mm2. It was 1,852 in
      the group of keratoconus and 751 in the group of bullous keratopathy. The average
      corrected visual acuity was 20/66 at 12 months. It was 20/45 in the group of
      keratoconus and 20/125 in the group of bullous keratopathy. The average
      astigmatism was 4.9 D, but running suture was still present at 12 months in most
      patients. Compared with graft survival after storage at +4 degrees C
      (retrospective paired control group), graft survival was higher after organ
      culture, but the difference does not reach the statistical significant threshold
      (p = 0.07). CONCLUSIONS: Organ culture is able to ensure the quality of corneal
      endothelium and then avoids non immune primary graft failure.

PMID- 8568160
TI  - [Evaluation of the desaturated Panel D-15. IV. Effect of the repetition of
      desaturated Panel D-15].
AB  - PURPOSE: The desaturated Panel D-15 was performed in a repetitive manner to
      determine whether such repetition improves test results, and, specially, whether
      repetition can eliminate false positives. METHODS: The study population included
      100 subjects with normal colour vision. The experimental procedure included:
      first the standard Farnsworth's Panel D-15 test, then the desaturated Panel D-15
      test performed three times consecutively by each subject. Qualitative evaluation
      with the Farnsworth D-15 classical diagram and quantitative evaluation with
      scores calibrated according to the ages of the subjects were used. RESULTS: The
      standard Panel D-15, performed first, was of no predictive value for the
      subsequent desaturated Panel D-15 (Cohen's K = 0.08). The desaturated Panel D-15
      performed three times consecutively gave evidence of improvement in all the
      studied variables, from the first to the third time: scores tended toward low
      values, lower mean score (from 85 to 42); more zero scores (from 17 to 32);
      smaller number of abnormal scores (from 16 to 3). At the first performance of the
      desaturated Panel D-15, there were 16% false positives. At the second, there were
      3%; and at the third, none of the initial false positives occurred. CONCLUSION:
      Three successive performances of the desaturated Panel D-15 were necessary and
      sufficient to eliminate all false positives and can also assess some abnormal
      results.

PMID- 8568161
TI  - [Study of the internal canthus with magnetic resonance imaging].
AB  - In oculoplastic surgery, the internal canthus is a particular feature of great
      importance. An analysis has been carried out with 10 MRI tests of the internal
      canthi and the authors will outline the major difficulties, before detailing a
      protocol which would enable further studies of pathological canthi.

PMID- 8568162
TI  - [Efficacy and tolerability of 2 presentations of eyedrops combining carteolol 2%
      and pilocarpine 2% in primary open-angle glaucoma and simple ocular
      hypertension].
AB  - PURPOSE: The aim of the study was to compare 2 combinations of eye drops
      containing 2% carteolol and 2% pilocarpine: LCM 1010: ready to use eye drops CBS
      341A: eye drops to be reconstituted (freeze-dried powder + solvent). METHODS:
      Ninety-seven patients with primary open angle glaucoma or simple ocular
      hypertension were included in a randomized, double-blind multicentric study
      comparing 2 parallel groups of treatment. Intra-ocular pressure was greater than
      21 mmHg with beta-blocker alone. One instillation of 2% carteolol-2% pilocarpine
      combination was given twice a day for one month. Before and after this treatment,
      intra-ocular pressure was measured at 9 am (12 hours after evening instillation)
      and at 11 am (2 hours after morning instillation). RESULTS: Both treatments
      reduced intra-ocular pressure by a comparable amount and there was no significant
      difference between groups at either measure: at 9 am: 2.11 +/- 2.39 mmHg (mean +/
      SD) for LCM 1010 1.79 +/- 1.73 mmHg for CBS 341 A p = 0.25 at 11 am: 3.75 +/-
      3.83 mmHg for LCM 1010 3.40 +/- 1.69 mmHg for CBS 341 A p = 0.42. Both eye drops
      were generally well tolerated. CONCLUSION: Efficacy and safety of ready to use
      eye drops 2% carteolol-2% pilocarpine combination proved to be comparable to that
      of eye drops to be reconstituted in the treatment of ocular hypertension poorly
      controlled by beta-blocker eye drops alone.

PMID- 8568163
TI  - [HTLV1 infection and sicca syndrome].
AB  - PURPOSE OF THE STUDY AND MATERIAL: A search for sicca syndrome was performed in
      54 HTLV 1 positive patients. Cases of sicca syndrome due to associated
      pathologies, or iatrogenic, were eliminated from this study. RESULTS: Lacrimal
      hyposecretion was found in 79% of the cases. Defective lacrimal quality was found
      in 86% of patients and a variable intensity coloration with the Fluorescine
      and/or with Rose Bengale was positive in 83% of cases. Histological study of the
      conjunctival print showed ocular dryness in 65% of the patients. Biopsy of the
      labial minor salivary glands showed a Gougerot-Sjogren syndrome in 71% of the
      cases. CONCLUSION: In our study, a sicca syndrome with varied gravity was found
      in 78% of cases.

PMID- 8568164
TI  - [Prognosis of retinal detachment in cytomegalovirus retinitis].
AB  - PURPOSE: To evaluate the incidence and the prognosis of retinal detachment in CMV
      retinitis in AIDS. To test intravitreal injections of ganciclovir into the
      vitreal cavity filled with silicone. METHODS: Among 136 eyes with CMV retinitis,
      15 (11%) had retinal detachment. Ten eyes underwent intraocular surgery with
      injection of silicone oil, one extraocular surgery and four eyes were not
      operated. Later, four eyes filled with silicone received intravitreal injections
      of ganciclovir. RESULTS: At 2 months, the retina was flat in all the operated
      eyes, with a visual acuity improved or stabilized in 8 cases (73%). Conversely,
      visual acuity was lost in all the unoperated eyes. The 14 intravitreal injections
      of ganciclovir performed in four eyes (which received 2, 3, 3 or 6 injections,
      respectively) were well tolerated. CONCLUSION: Surgery of retinal detachment in
      CMV retinitis usually allows the conservation of ambulatory visual acuity. Its
      indications must be discussed together with the patient, the ophthalmologist and
      the physician. Intravitreal injections of ganciclovir in vitreal cavity filled
      with silicone oil are possible.

PMID- 8568165
TI  - [Complication of keratoprosthesis of posterior fixation: retroprosthetic
      membranes. Apropos of 4 cases].
AB  - Keratoprosthesis represents the last solution for patients with bilateral corneal
      blindness or for monophthalm patients who cannot benefit from corneal grafts.
      Complications related to this technique are recalled together with an in-depth
      analysis of the problem of retroprosthesis membranes. The frequency of
      retroprosthesis membranes varies depending on the series reported, although it
      appears to be a more agreement on treatment and causes. Among 8 patients who
      underwent a KPF operation using the E. Lacombes technique, 50% of the cases had
      retroprosthesis membranes with an unusual thickness, vascularization and
      recurrent character. Emphasis was placed on early and intense intraocular
      inflammation.

PMID- 8568166
TI  - [Palpebral mycosis].
AB  - A 47-year-old man presented with a necrotic and haemorrhagic ulceration of the
      lower eyelid. He had a-one-year history of secondary hepatocarcinoma. The patient
      underwent excision biopsy of the lesion. Histological examination showed fungal
      spores, which could be candida albicans.

PMID- 8568167
TI  - [Anisocoria disclosing malignant lymphoma].
AB  - Intraocular lymphoma is a rare disease. We present a patient in which anisocoria
      led to the diagnosis of iris lymphoma and systemic malignant non Hodgkin's
      lymphoma.

PMID- 8568168
TI  - [Ocular siderosis: its management. Apropos of a case].
AB  - Siderosis bulbi, a rare ocular affection, occurs when an iron-containing foreign
      body is retained within the eye. The authors report the management of an
      unrecognized foreign body in one case.

PMID- 8568169
TI  - [Bilateral acute retinal necrosis in a patient with acquired immunodeficiency
      syndrome].
AB  - A case of bilateral progressive outer retinal necrosis occurred after herpes
      zoster ophthalmicus in a patient with acquired immunodeficiency syndrome. This
      case does not correspond to the classical picture of progressive outer retinal
      necrosis. The disease led to blindness despite intravenous therapy with acyclovir
      and foscarnet. PCR could not identify any virus in the aqueous humour, but VZV is
      evidenced in cerebrospinal fluid. Acute retinal necrosis is now clearly defined
      by the American Uveitis Society, which should allow to determine its incidence
      and risk factors. Herpes zoster usually precedes the acute outer retinal
      necrosis. The infectious theory (VZV, HSV, CMV) widely prevails over the immune
      theory. We prefer the virus genome identification in the aqueous humor or in the
      vitreous by PCR to confirm diagnosis rather than the specific antibody titration.
      Therapy consists in acyclovir, foscarnet and ganciclovir. But whatever the
      treatment, the visual prognosis is poor.

PMID- 8568170
TI  - [Chorioretinal manifestations in AIDS].

PMID- 8568171
TI  - [Treatment of ocular hypertension after trabeculectomy].

PMID- 8568172
TI  - [Breast cancer and hMG treatment: is there a relationship?].
AB  - The promoter effect of oestradiol in breast cancer, the higher risk of breast
      cancer in infertile nulliparous women and the increased use of treatments to
      include ovulation would suggest that the risk of cancer after this type of
      treatment might be affected. We thus evaluated the files of patients under 45
      years of age treated for breast cancer at the Bergonie Foundation. Six such cases
      were found. Due to the small number of cases observed to date, no statistical
      analysis could be performed. Nevertheless, several cases may have gone
      unrecognized or unpublished. Two hypothesis might be involved: the facilitating
      effect of stimulation on infraclinical or undiagnosed cancers, initiation of new
      cancers. We thus propose: a register to follow treated women in order to monitor
      the appearance of new cases of cancer, improved surveillance in patients with
      other associated risk factors.

PMID- 8568173
TI  - [Lymphocytic mastopathy. A case report and review of the literature].
AB  - Lymphocyte mastopathy is a benign disease of the breast with characteristic B
      cell aggression in the lobules. This cellular aggression generally occurs within
      a context of autoimmunity, such as insulino-dependent diabetes which is the most
      frequent.

PMID- 8568174
TI  - [Cowden's disease in a young girl: mammographic problems].
AB  - A 14-year-old girl consulted for multiple breast nodules which were found to
      result from Cowden's disease, also called multiple hamartomatosis. Mammography
      and sonography examinations were completed with nuclear magnetic resonance
      imaging after injection of paramagnetic contrast product. Cowden's disease is a
      rare condition resulting in the development of tumors in genodermatous tissue;
      The cause remains unknown. In cases involving the breast, cutaneous lesions are
      markers of precancerous development since cancer occurs in 28 to 30% of these
      cases.

PMID- 8568175
TI  - [Thromboembolism and ovarian hyperstimulation].
AB  - Three new cases of thromboembolic accidents involving the superior vena cave were
      associated with ovarian hyperstimulation and multiple pregnancy. On the basis of
      a review of the literature, three syndromes were individualized. First embolic
      arteries are infrequent and serious with an important morbidity; low doses of
      gonadotrophines is sufficient for causing this pathology. Second, thrombosis of
      the superior vena cava is late, during in vitro fertilization regimens with GnRH
      analogs complicated with serious hyperstimulation (degree III). Third, pregnancy
      is always present; pulmonary complications are very uncommon. Thrombosis of
      inferior vena cava is late, pregnancy is often present but women are frequently
      at risk of thromboembolic accident. Prevention of hyperstimulation is important.
      When present, HBPM is recommended for prevention of thromboembolism. Diagnostic
      of thrombosis is made with clinical examination and morphologic complementary
      exams such colour-vascular Doppler and magnetic resonance imaging. Curative
      treatment requires heparinization.

PMID- 8568176
TI  - [Hysterosonographic study of the uterine cavity].
AB  - OBJECTIVE: Evaluate the reliability, safety and performance of hysterosonographic
      assessment of the uterine cavity. MATERIALS AND METHODS: Hysterosonography was
      performed in 220 patients with injection of sterile saline into the uterine with
      a novel catheter. Among these patients, 132 patients then underwent a
      hysteroscopy or hysterectomy with a histology examination. RESULTS: There were 8
      failures: 2 synechiae, 3 atresias of the cervix, and massive reflux in 3 cases.
      No other complication occurring. Hysterosonography appeared to give more
      information on the uterine cavity than standard vaginal sonography. In cases with
      metrorrhage before menopause, the diagnosis was correct in 75.4% of the cases.
      Errors were related to confusion between polyp and hyperplasia. In post
      menopausal metrorrhagia, there was 92% agreement between sonography and
      histological results. Agreement was 86.3% in cases of infertility. CONCLUSION:
      Hysterosonography using saline solution injected with a novel catheter can be an
      excellent means of evaluating the uterine cavity and can completely replace
      classical hysterography, thus avoiding many exploratory hysterocopies.

PMID- 8568177
TI  - [Laparoscopic surgery of large uterine fibromas. Operative technique and
      results].
AB  - OBJECTIVE. To describe the technique of laparoscopic myomectomy for large myomas
      (5 cm and more) and to evaluate the results. RESULTS. Only myomas which are
      complicated (and/or resistant to properly conducted medical treatment) require
      surgical treatment. Between October 1, 1990 and October 31, 1994, we carried out
      72 laparoscopic myomectomies for intramural myomas measuring 5 cm or more, in 71
      patients. The operations lasted 130 +/- 60 min (range: 40-330 min). We converted
      to laparotomy for two cases (2.7%). We observed no serious per or postoperative
      complications. We never needed a repeat operation, whether by laparotomy or by
      laparoscopy. CONCLUSION. Despite these encouraging results, it must be remembered
      that the operation is lengthy and difficult and is reversed for laparoscopic
      surgeons perfectly familiar with endoscopic knot tying. Although it is a
      difficult technique, laparoscopic myomectomy is possible even for large myomas
      and those that are completely intramural. These results need to be assessed over
      the long term especially with respect to the risk of adhesions and the quality of
      the laparoscopic suture.

PMID- 8568178
TI  - [Ovarian carcinomas. Retrospective study of 318 cases].
AB  - OBJECTIVE: Evaluate the diagnosis of cancer of the ovary over time and
      histological type as a function of outcome. METHODS: Primary neoplasms of the
      ovary diagnosed at the Pathology Institute of Strasbourg between 1975 and 1984
      were reassessed to determine the outcome as recorded in the Bas-Rhin Cancer
      Register. RESULTS: Among the 845 primary neoplasms diagnosed, 318 were
      carcinomas. More than half of the cases (n = 162) were serous carcinomas followed
      by mucinous carcinoma (n = 60), endometrioid carcinoma (n = 53), clear-cell
      carcinoma (n = 13), and poorly differentiated carcinoma (n = 30). Diagnosis was
      consistent with time and independent of the pathologist. The patients were
      divided into three groups on the basis of survival. Longest survival was observed
      in patients with mucinous and endometrioid carcinoma, intermediary survival in
      those with serous and clear-cell carcinoma, and shortest survival in those with
      poorly differentiated carcinoma. CONCLUSION: The histological type of ovary
      carcinoma, independent of the stage of invasion, is a reliable predictive factor.

PMID- 8568179
TI  - [Surgical abdominal access for prolapse using a Vicryl composite lattice.
      Preliminary study].
AB  - OBJECTIVE: Promontory fixation is a reliable technique for genitourinary
      prolapsus. Results obtained with Mersurtures are good, but infectious episodes
      have been described and the fixation is rigid. The pelvic organs loose their
      mobility with possible functional impairment. To avoid these problems, we tested
      a composite implant composed of 60% absorbable polyglactine 910 (Vicryl) and 40%
      non-absorbable terephthalic polyester (Dacron). SUBJECTS AND METHODS: A series of
      32 patients with genito-urinary prolapsus were treated by one operator using the
      new material. Promontory fixation was performed in all cases, with at least one
      implant. The patients were followed for mean 24.2 months for evaluation of
      tolerance to the new material and the functional impact. These parameters were
      compared retrospectively with former experience with Mersutures. RESULTS: The new
      material was perfectly tolerated and no infectious complication was observed. The
      anatomic results were identical to those obtained with the Mersutures, giving
      93.4% good anatomic results, 68% cure rate for urinary incontinence and 20% major
      improvement in urinary incontinence. It was difficult to analyse results for
      sexual activity and digestive tract function. CONCLUSION: The Vicryl composite is
      useful for promontory fixation in patients with prolapsus. This material which
      reduces the amount of inert material remaining in the form of a thin lattice of
      highly flexible Dacron, should be tested prospectively to determine the
      functional benefit of prolapsus care.

PMID- 8568180
TI  - [Ethical problems with the current French practice in therapeutic abortions. Part
      2: survey by questionnaire in 15 french university hospitals].
AB  - OBJECTIVE: Determine the circumstances and conditions concerning ethical problems
      raised by medical abortions treated in a certain number of University Hospitals.
      METHODS: Survey using a questionnaire during the first three months of 1993 in 15
      gynaecology-obstetrics wards in University Hospitals in France. RESULTS: Fourteen
      responses were analysed. Usually with complementary open comments. CONCLUSION:
      Situations raising ethical problems concerning fetal medicine were encountered in
      approximately 5% of the pregnancies followed at the university Hospitals. Medical
      abortion was performed in 2% of the pregnancies. Gynaecologist-obstetricians
      prefer maintaining their control over prenatal diagnosis, especially when the
      outcome in medical abortion.

PMID- 8568181
TI  - [Ethical problems with the current French practice in therapeutic abortions. Part
      3: resolving moral dilemmas in fetal medicine].
AB  - OBJECTIVE: Based on the information acquired in the first two parts of this study
      and the data in the literature, to propose ethic codifications for solving moral
      dilemmas concerning fetal medicine. METHODS: Identification of situations where
      the object of the conflict is ethics: general methodology propositions for making
      individual decisions. RESULTS: In all cases a rigorous method is required, based
      on three main elements: a complete and well documented medical file; the opinion
      of the couple after appropriate participative communication; case by case
      collegial discussion. CONCLUSION: The methodology proposed underscores the roles
      played by health carers: obtain a medical file as complete as possible with prime
      emphasis on the infant; establish active communication with the parents giving
      greater value to their free examination of the situation; collegial discussion in
      order to be pertinent social partners.

PMID- 8568182
TI  - [Ultrasonic signs of fetal toxoplasmosis. Review of the literature].
AB  - OBJECTIVE: Evaluate the frequency and discuss the mechanisms and the prognostic
      value of sonographic anomalies observed during the surveillance of seroconversion
      for toxoplasmosis during pregnancy. METHODS: Cases of seroconversion during
      pregnancy were collected from 6 teams working with similar protocols. There were
      2,168 seroconversions. We focused on ultrasound anomalies reported. RESULTS:
      Ultrasound anomalies were reported in 48 cases including the 168 fetuses with
      proven contamination (fetal blood or amniotic fluid sample), i.e. 2.2% (48 cases
      out of 2,168) of the seroconversions and 28% (48 cases out of 168) of the
      contaminated fetuses. There were multiple lesions in 44% of the cases. Brain
      calcifications had been found in utero in 44% of the newborns with such
      anomalies. No case of microcephalia was reported. Isolated hepatomegalia (4
      cases) was not an indication for medical abortion. Isolated ascitis can regress
      after antiparasite treatment (2 cases). Medical abortions were performed in 51%
      of the cases (34 cases out of 66) on the basis of ultrasound findings.
      CONCLUSION: Ultrasound examination is reliable but can only detect late,
      constituted and often irreversible lesions. Nevertheless, this examination can
      help in deciding on medical abortion.

PMID- 8568183
TI  - [Prolonged pregnancy. Review of the literature].
AB  - There have been various estimations of the frequency of postdate pregnancies. On
      the average, 10% of all pregnancies exceed 42 weeks amenorrhoea with a range from
      4 to 14% according to the authors. Rates vary with use of ultrasound examinations
      early, avoiding false dating and induced labour. A pregnancy becomes a pregnancy
      at risk at the end of the 41st week of amenorrhoea. Fetal maturity may be
      affected by a disease process or due to individual or ethnic variations. The
      potential danger of prolonged pregnancy is inhalation of meconium prepartum.
      Expulsion of meconium is both a frequent consequence of fetal distress and the
      result of increased intestinal reactivity. There does not appear to be agreement
      on the degree of risk of sudden death at the end of pregnancy, although the risk
      does appear to exist. Surveillance should include recording fetal heart rate
      under basal conditions and an assessment of the amniotic fluid volume with
      ultrasounds. The Doppler technique is currently under study. When the status of
      the cervix is favourable, labour may be induced by rupturing the membranes of
      with a perfusion of Syntocinon. When the status of the cervix is unfavourable,
      prostaglandin E2 is applied intravaginally or intracervically with a gel.
      Therapeutic trial published to date do not demonstrate any advantage over
      cesarean section or fetal morbidity. The safety of the procedure has not been
      proven. Randomized trials comparing systematic induction of labour with a wait
      and-see attitude have not given a definitive answer. Only two trial have shown a
      significant advantage of systematic induction of labour. The others have shown
      that the rate of cesarean section and neonatal morbidity are comparable in the
      two groups.

PMID- 8568184
TI  - [Association of Takayasu's arteritis, pregnancy and Still's disease].
AB  - Two pregnant patients presented with Takayasu's disease predominating in the
      major branches of the aorta. There was no extention below the diaphragm and no
      complications. One of the patients had Still's disease which is a predominantly
      cutaneous form without chronic arthritis. Both pregnancies were uneventful
      excepting dysgravidia in one case. Two eutrophic infants were born at term. The
      risk of Takayasu's arteritis associated with pregnancy, as reported in the
      literature, is mainly due to the consequences of arterial hypertension with pre
      eclampsia (60%), heart failure and cerebral vascular events (5%). The major fetal
      risk is in utero death (2 to 5%), but intra-uterine growth retardation is more
      frequent (18%). The risk is greatest during the third trimester and during the
      perinatal period. Fetal involvement is greatest in sever cases and in those
      treated late. Prevention is based on the initial work-up to identify the disease
      and possible complications, programming pregnancies and increasing surveillance
      during periods of risk, defining the delivery route with cesarean section
      reserved for complications of arteritis (30%), and planned labour with
      instrumental extraction and epidural anaesthesia with control of the blood
      pressure. Still's disease has no particular consequence on pregnancy, although
      sequellae of chronic arthritis of the pelvis may have an impact on obstetrical
      technique. An association with Takayasu's disease is rare with only one case
      being reported in the literature; aetiopathology remains unknown.

PMID- 8568185
TI  - [Placenta accreta. Ten cases].
AB  - A retrospective analysis of 10 cases of placenta accreta observed from 1983 to
      1993, all confirmed histologically, were reviewed at the Gynaecology-Obstetric B
      ward of the Charles Nicolle Hospital in Tunis. The incidence of this placental
      anomaly is 1 for 7,139 births. The condition is usually discovered due to
      excessive bleeding at delivery. In 10 cases, hysterectomy was required for
      haemostasis. There were 3 maternal deaths. The insertion of the placenta on a
      uterin scar is highly suggestive of placenta accreta. The increase in the
      incidence of this pathology over the last years is probably related to the
      increase in the number of cesarean sections. When observed, hysterectomy provides
      the best chances of survival.

PMID- 8568186
TI  - [Preliminary study of the use of fetal pulse oximetry during labor].
AB  - OBJECTIVE: To assess continuous monitoring of fetal blood oxygen staturation
      (SpO2) during labour using a fetal pulse oxymeter. STUDY DESIGN: Preliminary
      results obtained with the Nellcor N-400 fetal pulse oxymeter at the Maternite
      Port-Royal-Baudelocque between November 1992 and November 1993 in cases of
      abnormal fetal heart rate are presented. We analyzed: the correlation between
      SpO2 during labour and cord vein pH as well as Apgar score, the correlation
      between changes in SpO2, expressed as a desaturation index, and cord vein pH as
      well as Apgar score. The negative predictive value of oxymetry was assessed.
      RESULTS: We found a significant positive correlation between the last SpO2
      measurement during labour and umbilical vein pH as well as 1 minute Apgar score.
      We observed a highly significant correlation between the index of desaturation
      and cord vein pH as well as 1 minute Apgar score. No neonatal pH below 7.20 was
      observed when SpO2 was > or = 40% during labour. The negative predictive value of
      oxymetry was 100% in this short series of patients. CONCLUSION: If these results
      were confirmed in a larger series of patients, a normal SpO2 value during labour
      could be reassuring in case of abnormal fetal heart rate.

PMID- 8568188
TI  - [Should we still use the Burch procedure?].

PMID- 8568187
TI  - [Cesarean section trends at the Toulouse University Hospital, from 1983 to 1993.
      Determinants and consequences].
AB  - OBJECTIVE: To examine the factors accounting for the increase in rate of cesarean
      section, between 1983 and 1993 (from 13.0% to 19.5%) in Toulouse University
      Hospital, a tertiary level center. DESIGN: Retrospective study of all single
      deliveries, excluding deaths in utero, between 1983 and 1993. RESULTS: Half the
      increase in overall rate was due to the numerical increase in women with a
      cesarean section history. The percentage of cesarean sections in these patients
      remained constant at 79% over this period. For the other patients, the increase
      in rate was due partly to an increase in risk factors, but mainly to a change in
      obstetric practice with a marked increase in elective cesarean section (70% of
      all cesarean sections in 1993). Major complications in the mothers were
      relatively rare, albeit significantly more frequent in the cesarean cases. Over
      the study period the percentage of infants requiring intensive care remained
      constant for the vaginal deliveries but declined for the cesarean sections.
      CONCLUSION: The increased rate of cesarean sections has not led to any increase
      in maternal complications, and appears to have had a small favorable influence on
      infant morbidity.

PMID- 8568189
TI  - Pattern of drug therapy in home management of diarrhoea in rural communities of
      Nigeria.
AB  - A prospective study was carried out in 72 rural communities in Nigeria to
      determine the pattern of drug therapy and other treatment modalities in case
      management of diarrhoea at home. The communities were selected using the cluster
      sampling technique, and the survey was carried out using the standard methodology
      of WHO/CDD diarrhoea case management and morbidity. A total of 9,293 children
      aged less than 5 years were studied, of which 488 had diarrhoea in the preceding
      24 hours of the medical examination. Oral rehydration salts (ORS) solution and
      drugs were used by 20.1%, of the children ORS alone by 2.7%, home-based fluids
      alone by 21.7%, drugs and salt-sugar solution (SSS) by 31.8%, and drugs and other
      home-based fluids by 23.7%. The drug-use rate was 75.6%, and polypharmacy
      occurred in 56.9%. The injection-use rate was 18.4%. Antibiotics (40.3%),
      antiprotozoals (24.6%), and antidiarrhoeals (15.3%) were the main groups of drugs
      used. The government doctors, health workers, pharmacists, and patent medicine
      dealers were the main sources of prescription and supply of drugs. The village
      health workers, traditional birth attendants, and traditional doctors, who
      together provided significant proportion of these functions, are an important
      group requiring training.

PMID- 8568190
TI  - Efficacy and tolerance of insoluble carob fraction in the treatment of
      travellers' diarrhoea.
AB  - The water-insoluble carob fraction (fraction insoluble caroube, FIC, Nestle) has
      been successfully used in the treatment of infantile diarrhoea. To investigate
      the efficacy and toxicity of FIC (1970 mg to be taken every 2 hours over a 48
      hour period except during sleeping time) in the treatment of travellers'
      diarrhoea in adults, a double-blind, computer randomized, placebo-controlled
      study was conducted. Of the 755 volunteers recruited at the Zurich University
      Vaccination Centre, 628 (83.5%) returned their questionnaires. Among them, 164
      (27.7%) had diarrhoea, but only 69 (42%) used the trial medication correctly; the
      others were rated non-complaint. No significant difference in efficacy (p = 0.12)
      or adverse effects were observed in the two study groups. In conclusion, FIC,
      although showed a positive trend, was not efficacious.

PMID- 8568191
TI  - Role of enteric nervous system in Shigella dysenteriae type 1 toxin-induced fluid
      secretion in rabbit ileum.
AB  - Intracellular-free calcium concentrations were measured in the intestinal
      epithelial cells isolated from the rabbit ileum treated with Shigella dysenteriae
      type 1 toxin. There is almost a five-fold increase in the [Ca+2]i levels in the
      epithelial cells isolated from the toxin-treated rabbit ileum compared to
      control. The [Ca+2]i levels were also measured in the presence or absence of
      tetrodotoxin, a neurotoxin, and atropine, a muscarinic cholinergic antagonist.
      These drugs significantly decreased the [Ca+2]i levels of the cells isolated from
      the toxin-treated rabbit ileum. Furthermore, the unidirectional fluxes of Na+ and
      Cl- were determined in both the S. dysenteriae type 1 toxin-treated and control
      rabbit ileum. Dantrolene significantly stimulated net absorption of these ions in
      the toxin-treated ileum, suggesting the involvement of [Ca+2]i in the regulation
      of intestinal electrolyte transport. To evaluate the role of neural mechanisms,
      the transport of these ions was also determined in the presence and absence of
      tetrodotoxin and atropine. The presence of these drugs caused significant
      absorption of Na+ and Cl- in the toxin-treated compared to their absence. These
      findings suggest that the enteric nervous system plays an important role in S.
      dysenteriae type 1 toxin-induced diarrhoea, and the release of neurotransmitters
      causes changes in the intracellular calcium levels, ultimately changing
      electrolyte transport across the rabbit ileum.

PMID- 8568192
TI  - Enterotoxin production and plasmid profiles in Salmonella typhimurium isolated
      from man.
AB  - One hundred twenty-six isolates of Salmonella typhimurium from various clinical
      sources were tested for enterotoxin production and characterization of plasmid
      profile. Cell-free culture supernates and polymyxin B extracts of all the strains
      were assayed by rabbit ileal loop and skin permeability tests. Enterotoxic
      activity was detected in culture supernates of 32 strains. Twenty-one strains by
      both rabbit ileal loop and skin permeability tests, nine strains by skin
      permeability test, and two strains by rabbit ileal loop test were positive. Live
      culture of three enterotoxic strains, positive in culture supernates produced
      ileal secretion. Polymyxin B extracts from 6 hours and 18 hours broth cultures of
      all the strains were devoid of enterotoxicity. Ileal mucosa exposed to culture
      supernate of enterotoxigenic strains showed swollen and blunted villi with
      submucosal oedema while those exposed to polymyxin B extracts showed shortening
      of villi and sloughing of epithelial lining. Plasmid profiles of enterotoxigenic
      strains were heterogenous and grouped into 20 different profiles. No correlation
      could be established between plasmid profile, R-pattern, and enterotoxin
      production.

PMID- 8568193
TI  - Relationship between enterotoxicity and multiple drug resistance in Aeromonas
      spp.
AB  - One hundred forty-seven isolates of Aeromonas spp., including 54 from diarrhoeal
      patients and 93 from the environmental sources, were examined for drug
      sensitivity and enterotoxin production. One hundred and fifteen (78%) isolates
      that included all A. hydrophila, 60% of A. sobria and 89% of A. caviae showed
      resistance to one or more antibiotic(s). Most (65%) of the resistant isolates
      caused fluid accumulation in rabbit ileal loops, of these 57% were A. hydrophila,
      69% of A. sobria and 65% A. caviae, whereas only a few drug-sensitive isolates
      did so. Multiple drug-resistant isolates caused comparatively more fluid
      accumulation than the drug-sensitive isolates. Furthermore, significant
      difference of ileal fluid accumulation was observed with the increase in the
      number of resistance markers. This study suggests that there is some association
      between multiple drug resistance and enterotoxicity of Aeromonas strains,
      regardless of their source of isolation and species.

PMID- 8568194
TI  - Vibrio cholerae non-O1 as a causal pathogen in cholera patients in Yangon,
      Myanmar.
AB  - Vibrio cholerae non-O1 was studied in patients with rice watery diarrhoea
      admitted to the Infectious Diseases Hospital, Yangon. The study was conducted
      during 1993-1994 to determine the association of the pathogen with the disease.
      Altogether 771 rectal swabs were collected and examined. V. cholerae were
      isolated by the standard methods. The seasonal, age and sex distribution,
      serotyping and susceptibility of these isolates to antibiotics were investigated,
      V. cholerae were isolated from 233 (3O.2%) samples. Among them, V. cholerae O1
      were isolated from 117 (5O%) samples and V. cholerae non-O1 from 116 (5O%)
      samples. The seasonal, age and sex distribution was identical in both V. cholerae
      O1 and V. cholerae non-O1 groups. V. cholerae O139 was isolated during February
      1994. Thus V. cholerae non-O1 was also one of the causal pathogens of cholera,
      like V. cholerae O1 in this community.

PMID- 8568195
TI  - Serotype distribution and antimicrobial susceptibility of Shigellae isolated from
      diarrhoeal patients in Yangon, Myanmar.
AB  - In Myanmar there is a changing pattern in the prevalence of Shigella strains with
      an increasing antimicrobial resistance, and, thus the serotype prevalence and
      antibiotic sensitivity pattern of Shigellae were studied in 1993. Dysenteric
      stool samples were collected from the laboratory of Infectious Diseases Hospital,
      Yangon during January-June 1993. The Shigella isolates were identified by the
      standard bacteriologic procedures. Four hundred and sixty stool samples
      containing blood and mucous were collected in this study, and Shigella spp. were
      isolated from the 108 (23.5%) samples. The increasing antimicrobial resistance of
      shigellosis from 1980 to 1993 in this community was also discussed.

PMID- 8568197
TI  - Bibliography on diarrhoeal diseases.

PMID- 8568196
TI  - Abundance of Aeromonas spp. in river and lake waters in and around Dhaka,
      Bangladesh.
AB  - Aeromonas spp. are widely distributed in the aquatic environment. In Bangladesh,
      seasonal distribution of these organisms in aquatic environment was studied
      during July 1986-August 1987. Water, sediment, plant, and plankton samples were
      collected monthly from the Dhanmondi lake and the Buriganga river during the
      study period. Aeromonas spp. were isolated from all samples throughout the year.
      The seasonal peak of Aeromonas spp. was observed in warmer months (April-May) in
      the surface waters. In the sediment, the highest peak was observed in March and
      August. In most plants, the highest peak was observed during the winter months
      (December-February). In the plankton samples of the Dhanmondi lake and the
      Buriganga river, the highest counts were obtained in July and February
      respectively. In both the sampling sites, plants were observed to contain more
      Aeromonas than did the water and sediment samples. The prevalence of Aeromonas
      spp. throughout the year in aquatic environment suggests the autochthonous nature
      of these organisms and that there is an association of Aeromonas with the aquatic
      environment.

PMID- 8568198
TI  - Nosocomial pertussis in the nineties.

PMID- 8568199
TI  - Containment of pertussis in the regional pediatric hospital during the Greater
      Cincinnati epidemic of 1993.
AB  - OBJECTIVE: To describe methods of preventing nosocomial pertussis in patients,
      employees, and visitors to a hospital during a communitywide epidemic in Greater
      Cincinnati. DESIGN: Six-month descriptive study of the methods, effectiveness,
      and cost of a program to prevent nosocomial pertussis. SETTING: Three hundred
      sixty-one bed, tertiary-care, university, pediatric hospital. RESULTS: We
      educated 3,764 hospital employees about pertussis. We evaluated 206 employees
      with respiratory illnesses, based on clinical presentation, pertussis exposure,
      and work setting. Eighty-seven had pertussis: 84 coughed for > or = 2 weeks
      (outbreak clinical case definition), 65 had paroxysms, 27 whooped, 22 had
      posttussive emesis, and 13 were positive by direct fluorescent antibody or
      culture for Bordetella pertussis. Seventy-nine employees were sent on 5-day
      furloughs. Six hundred twenty-two employees received 14 days of erythromycin
      (579) or trimethoprim-sulfamethoxazole (43). Symptomatic patients were identified
      at triage in the emergency department and placed in respiratory isolation.
      Suspect pertussis cases were admitted in respiratory isolation. Among 49 toddlers
      who were given erythromycin and managed in "coughing respiratory cohorts," eight
      had proven pertussis. Inpatients were restricted to assigned nursing units.
      Respiratory masks were required for those entering the test referral center,
      where more than 3,500 pertussis cultures were performed. Hospitalwide visitor
      restriction was enforced for those aged 14 years or younger and for those with
      respiratory symptoms. Only parents and guardians were permitted to visit the
      newborn intensive care unit. A child-care service managed 488 inpatient sibling
      visitors. Four symptomatic children in the employees' child-care center were
      excluded pending physician evaluation; one had pertussis. CONCLUSIONS: Control
      measures appeared effective. Pertussis occurred in 87 (2%) employees. Among 102
      children hospitalized with pertussis, respiratory isolation was delayed in nine
      cases, and one case was nosocomial. Program expenses totalled $85,400. Adult
      booster immunization with acellular pertussis vaccine might represent the safest
      and least expensive strategy for preventing epidemic pertussis, and controlled
      trials of acellular pertussis vaccine in hospital employees are needed.

PMID- 8568200
TI  - Vertical transmission of Citrobacter diversus documented by DNA fingerprinting.
AB  - OBJECTIVE: To confirm the vertical transmission of Citrobacter diversus from a
      mother to her infant and to evaluate the epidemiologic usefulness of a new
      automated procedure for analysis of polymerase chain reaction (PCR)-generated DNA
      fingerprints. DESIGN: Repetitive element-based PCR (rep-PCR) analysis of C
      diversus isolates from the blood and amniotic fluid of a mother and the blood of
      her infant was performed. Unrelated C diversus isolates also were characterized
      and compared with the isolates from mother and infant. DNA fingerprints were
      generated by gel electrophoresis of PCR products derived from either unlabeled
      standard repetitive sequence-based oligonucleotide primers or fluorescent
      primers. The standard rep-PCR fingerprints were analyzed by visual inspection.
      The fluorescent primers were used in fluorophore-enhanced rep-PCR (FERP), and the
      FERP DNA fingerprints were analyzed by an Applied BioSystems (ABI) Model 373A
      laser scanning unit equipped with Genescan 672 software (Applied Biosystems, Inc,
      Foster City, CA). SETTING AND PATIENTS: A mother and her newborn infant, both
      with invasive disease due to C diversus, in an urban tertiary-care hospital.
      RESULTS: The DNA fingerprints of the maternal blood, amniotic fluid, and infant
      blood isolates of C diversus were identical by both visual inspection of ethidium
      bromide-stained agarose gels and computer-aided analysis of FERP patterns. These
      strains appeared to differ from all but one control isolate, which had been
      collected 7 years earlier in the same city in which the infant was born.
      CONCLUSIONS: Vertical transmission of C diversus from mother to infant can occur
      in utero. Automated analysis of rep-PCR-generated DNA fingerprints derived using
      fluorescent primers is an objective means for comparing isolates of C diversus
      and in all likelihood would be useful for other species of bacteria that possess
      repetitive elements.

PMID- 8568201
TI  - An outbreak of needlestick injuries in hospital employees due to needles piercing
      infectious waste containers.
AB  - OBJECTIVES: To investigate the cause of an outbreak of needlestick injuries
      (NSIs) in hospital employees. SETTING: A 700-bed university hospital. DESIGN:
      Outbreak investigation, laboratory evaluation of a medical waste disposal device,
      cost analysis. METHODS: Employee health department records were reviewed of
      workers suffering sticks from needles piercing fiberboard-contaminated material
      containers (CMCs). A laboratory evaluation of needle-puncture resistance
      properties of the CMCs was performed using a testing apparatus. The cost of a
      hospital waste disposal program using fiberboard CMCs was compared with the cost
      of a program using rigid plastic (polypropylene) boxes. RESULTS: During 40 months
      of surveillance in 1986 and from 1989 to 1991, only one NSI had occurred from a
      needle piercing a CMC. During 9 months in 1993, 13 NSIs occurred due to needles
      piercing CMCs (P < .001). No clinical illness resulted from the NSIs. The
      outbreak was halted by a temporary change to plastic (polypropylene) boxes for
      sharps disposal ($4.92 to $23.33/cu ft) until receipt of a box with a newly
      designed solid fiberboard liner ($1.25/cu ft). CMC liners used during the
      epidemic had a mean needle puncture resistance of 527 g, as compared with 660 g
      for liners used before the outbreak (P < .001). The new solid fiberboard liner
      has a mean puncture resistance of 1,765 g. A program of waste disposal using
      fiberboard CMCs was found to cost approximately one-seventh the cost of a program
      using plastic boxes for disposal of infectious waste. CONCLUSION: A program for
      infectious waste disposal using fiberboard CMCs can be safe and cost-effective if
      appropriate standards for puncture resistance are met.

PMID- 8568202
TI  - Recovery of vancomycin-resistant enterococci on fingertips and environmental
      surfaces.
AB  - OBJECTIVE: To determine the recovery of vancomycin-resistant enterococci (VRE) on
      fingertips, gloved fingertips, and environmental surfaces commonly encountered in
      the healthcare setting, and to examine the importance of handwashing on the
      removal of these organisms. DESIGN: Two clinical isolates of VRE (Enterococcus
      faecalis and Enterococcus faecium) were inoculated onto the hands of healthy
      human volunteers and the following environmental surfaces: countertops, bedrails,
      telephones, and stethoscopes. Following inoculation, samples were obtained at
      various time intervals to determine rates of recovery of organisms. To evaluate
      the effects of handwashing on enterococcal recovery, two different soap
      preparations were tested. Hands were washed with water alone or with one of the
      soaps and water. The soap and water studies were performed with a 5-second and a
      30-second wash. RESULTS: Both enterococcal strains survived for at least 60
      minutes on gloved and ungloved fingertips. The E faecalis was recoverable from
      countertops for 5 days; the E faecium persisted for 7 days. For bedrails, both
      enterococcal species survived for 24 hours without significant reduction in
      colony counts. The bacteria persisted for 60 minutes on the telephone handpiece
      and for 30 minutes on the diaphragmatic surface of the stethoscope. A 5-second
      wash with water alone resulted in virtually no change in recovery of enterococci;
      a 30-second wash with water plus either soap was necessary to eradicate the
      bacteria from hands completely. CONCLUSION: VRE are capable of prolonged survival
      on hands, gloves, and environmental surfaces. Hands should be washed thoroughly
      and gloves removed following contact with patients infected or colonized with
      these multidrug-resistant bacteria. Finally, environmental surfaces may serve as
      potential reservoirs for nosocomial transmission of VRE and need to be considered
      when formulating institutional infection control policies.

PMID- 8568203
TI  - Percutaneous injury analysis: consistent categorization, effective reduction
      methods, and future strategies.
AB  - OBJECTIVE: To report the results of an 8-year analysis of percutaneous injuries
      (PI), to describe interventions to decrease these injuries, and to discuss future
      prevention strategies. DESIGN: Using consistent methods, 881 percutaneous injury
      reports were reviewed, categorized, and analyzed from 1986 through 1993. SETTING:
      A 620-bed acute-care county teaching hospital located in San Jose, California,
      that is affiliated with Stanford University Medical School, Palo Alto,
      California. PARTICIPANTS: Employees of Santa Clara Valley Medical Center who
      reported percutaneous injuries from 1986 through 1993. INTERVENTIONS: Placement
      of needle disposal containers in all patient care areas, 1987; education, 1987 to
      present; communication of percutaneous injury analyses to all departments, 1988
      to present; and safety product evaluation and purchases, 1991 to present.
      RESULTS: The total number of PI decreased by 65% (P = .0007) from 1986 through
      1993. Recapping injuries decreased from 1986 through 1993 by 88% (P < .0002);
      interventions that included convenient placement of needle disposal containers
      and consistent annual education may have contributed to this decrease. Injuries
      from manipulating intravenous lines or heparin locks decreased in 1992 (P < .03)
      after purchase of a needleless system for intravenous lines. Injuries from
      improper disposal or from abrupt patient movement did not decrease significantly
      over the 8-year period. CONCLUSIONS: This institution has conducted percutaneous
      injury analysis for 8 years, utilizing consistent reviewers and categorization
      methods. Successful interventions have reduced recapping injuries, injuries from
      manipulating intravenous lines/heparin locks, and the overall numbers of PI. The
      categories of "Improper Disposal" and "Patient Moved Abruptly" present challenges
      for future reductions, as well as the recently identified problem of staff not
      using available safety devices or using them improperly.

PMID- 8568204
TI  - Molecular heterogeneity of Acinetobacter baumanii isolates during seasonal
      increase in prevalence.
AB  - OBJECTIVE: To study the epidemiology of Acinetobacter baumanii during a period of
      increased seasonal prevalence. DESIGN: Descriptive molecular and clinical
      epidemiologic study of A baumanii isolates from 1990 through 1992. SETTING: A 770
      bed urban, acute, tertiary-care university hospital. RESULTS: During 1990 through
      1992, the rate of A baumanii isolations was 30.4 per 1,000 culture isolations
      during the summer, compared to 12.6 per 1,000 culture isolations during the fall,
      winter, and spring (P < .000001). There were 320 isolates identified among 260
      patients during this time. Eighty-one patients with isolates available were
      identified for evaluation; they ranged in age from 2 months to 95 years. Pulsed
      field gel electrophoresis (PFGE) typing showed that 59 (83%) of 71 typed isolates
      had distinct PFGE patterns. There were three small clusters of isolates with the
      same PFGE patterns, suggesting cross-transmission in those instances.
      CONCLUSIONS: A seasonally increased prevalence of A baumanii largely associated
      with device-related nosocomial infections in severely ill patients was noted over
      a 3-year period. Although there were isolated instances of cross-transmission,
      most isolates had distinct PFGE patterns. Clonal dissemination of a single strain
      was not responsible for the seasonal increased prevalence of A baumanii. PFGE
      typing was useful in directing control efforts.

PMID- 8568206
TI  - Treatment of Hickman catheter sepsis using antibiotic lock technique.
AB  - Antibiotic lock therapy, an alternative treatment for Hickman catheter sepsis,
      was evaluated in six recipients of prolonged outpatient intravenous therapy.
      Twenty-two episodes of catheter sepsis were identified, involving coagulase
      negative staphylococci (11), gram-negative bacilli (3), gram-positive bacilli
      (1), yeast (4), and mixed bacteria or fungi (3). In a select group of patients,
      treatment was successful 92% of the time.

PMID- 8568205
TI  - Epidemiologic investigation of an outbreak of coagulase-negative Staphylococcus
      primary bacteremia in a newborn intensive care unit.
AB  - Infections due to coagulase-negative Staphylococcus (CNS) are an ever-increasing
      nosocomial problem, particularly in the pediatric population. The authors
      describe a cluster of three primary bloodstream infections due to CNS in a
      newborn intensive care unit that occurred between November 23 and December 2,
      1992. Two children died as a direct consequence of the bacteremia; at autopsy,
      one had a large bacteria-containing thrombus extending from the insertion site of
      a central catheter to the superior vena cava. The children were placed in
      isolation, and the nursing and medical staff were given topical nasal mupirocin.
      Plasmid analysis performed later disclosed three different blood isolates that
      also were different from any of the staff's nasal isolates. The authors concluded
      that molecular methods such as plasmid analysis are important tools in
      identifying true outbreaks and can prevent needless interventions, such as those
      during this cluster.

PMID- 8568207
TI  - Hospital epidemiology in smaller hospitals.
AB  - In hospitals with 200 to 300 beds, hospital epidemiologists serve primarily as
      medical and epidemiology consultants to the infection control practitioners, as
      advocates for the infection control programs, and as chairpersons of the
      infection control committees. Because smaller hospitals often have limited
      resources for infection control, surveillance and control activities must focus
      on issues that have caused problems for the facility and on compliance with
      mandates and recommendations made by healthcare agencies. The clinical
      microbiology laboratory plays an important role in ongoing surveillance
      activities and often is responsible for performing cultures obtained during point
      prevalence culture surveys or outbreak investigations. Because laboratory support
      often is limited, the indications for obtaining a culture from patients,
      personnel, or the inanimate environment for infection control purposes must be
      reviewed and discussed carefully with the clinical laboratory in advance.

PMID- 8568208
TI  - A letter from Oliver Wendell Holmes, 1809-1894: in memory of the centennial of
      his death.

PMID- 8568209
TI  - Molecular phylogeny of the red panda (Ailurus fulgens).
AB  - The phylogenetic placement of the red panda (Ailurus fulgens) and the giant panda
      (Ailuropoda melanoleuca) has been an evolutionary enigma since their original
      descriptions in the nineteenth century. A series of recent molecular analyses led
      to a consensus that the giant panda's ancestors were derived from early bears
      (Ursidae), but left unsettled the phylogenetic relationship of the red panda.
      Previous molecular and morphological phylogenies were inconclusive and varied
      among placement of the red panda within the raccoon family (Procyonidae), within
      the bear family (Ursidae), or in a separate family of carnivores equidistant
      between the two. To examine a relatively ancient (circa 20-30 million years
      before the present, MYBP) phylogenetic divergence, we used two slowly evolving
      genetic markers: mitochondrial 12S rRNA sequence and 592 fibroblast proteins
      resolved by two dimensional gel electrophoresis. Four different carnivore
      outgroup species, including dog (Canidae: Canis familiaris), cat (Felidae: Felis
      catus), fanaloka (Viverridae: Fossa fossa), and mongoose (Herpestidae: Galidia
      elegans), were selected to identify the root of the phylogenetic topologies.
      Phylogenetic reconstruction by distance-based methods, maximum parsimony, and
      maximum likelihood clearly indicate a distinct bifurcation forming the Ursidae
      and the Procyonidae. Further, our data consistently place the red panda as an
      early divergence within the Procyonidae radiation and confirm the inclusion of
      giant panda in the Ursidae lineage.

PMID- 8568210
TI  - Hybridization between tetraploid and diploid species of treefrogs (Genus hyla).
AB  - An indirect analysis of female meiotic mechanisms in the tetraploid (4n = 48)
      grey treefrog, Hyla versicolor, was performed by examining artificially produced
      hybrids. First generation hybrids between a H. versicolor female from Canada (4n
      = 48) and a H. arborea male from France (2n = 24) were all triploid and appeared
      to contain two sets of chromosomes from H. versicolor and one set from H.
      arborea. Males and females were produced in equal numbers but testes in general
      were more completely developed than ovaries. Electrophoretic analysis of selected
      allozyme loci suggested that gene products from the two parents were not equally
      expressed. Backcross hybrids were triploid, tetraploid, and pentaploid but did
      not appear to contain recognizable chromosomes from the H. arborea grandparent.
      Allozymes from these hybrids indicated that only H. versicolor alleles were
      expressed, as none of the distinctive H. arborea alleles present in the triploid
      male parent were present in the offspring. It was concluded that preferential
      pairing of chromosomes and gene regulatory biases may help to explain factors
      that relate to the ability of tetraploids to hybridize with even distantly
      related taxa and may be involved in the rediploidization process that usually
      follows polyploidization.

PMID- 8568211
TI  - RAPD variation within and among natural populations of trembling aspen (Populus
      tremuloides Michx.) from Alberta.
AB  - This article described the population structure of trembling aspen (Populus
      tremuloides Michx.) in Alberta, a dioecious tree with continuous and wide
      distribution, and with a primary mode of reproduction through suckering. We
      studied random amplified polymorphic DNA (RAPD) variation in 249 trees from eight
      natural populations. Trees within a population were a minimum of 200 m apart to
      decrease the risk of sampling ramets of a single ortet. Of a total of 28
      amplified RAPD products (bands) from five random oligonucleotide primers, the
      frequencies at seven (25%) were heterogeneous across populations and the
      percentage of polymorphism averaged 90.2 per population. Estimates of Shannon's
      phenotypic diversity index ranged between 0.58 and 0.69 among populations,
      averaging 0.65. There were 246 multiband phenotypes among the 249 trees; three
      were each shared by two trees from different populations and the remaining 243
      were unique. Thus, trees within populations probably were different clones.
      Analysis of molecular variance partitioned the RAPD variation into the among- and
      within-population components. The within-population component accounted for 97.4%
      of the variation and was significantly different from zero at the 2% level of
      probability. The among-population component, although accounting for only 2.6% of
      the variation, was significantly different from zero at the 1% level of
      probability. Pairwise tests for the homogeneity of the RAPD variance between
      populations suggested significant divergences among 18 of the 28 (64%) population
      pairs.

PMID- 8568212
TI  - Structure of African elephant populations.
AB  - The structure of elephant populations from east and south Africa has been
      analyzed by Georgiadis et al. (1994) on the basis of restriction site variation
      of mitochondrial DNA. They used F statistics based on identity by descent in
      tests for subdivision and reached the conclusion that there was a significant
      differentiation at the continental level, but that "populations were not
      significantly subdivided at the regional levels." The data were reanalyzed by
      Monte-Carlo permutation tests where population subdivision was tested by using F
      statistics based on partitioning the total haplotype diversity among populations.
      This resulted in identical conclusions at the continental level, but revealed in
      addition a significant subdivision at the regional level indicating haplotype
      frequency differences among the populations.

PMID- 8568213
TI  - Heterozygosity of F2 from two segregating populations.
AB  - Exact formulas that predict the average inbreeding coefficient and heterozygosity
      of an F2 generation derived from two segregating populations were developed. When
      population sizes are sufficiently large, the heterozygosity of the F2 is one-half
      of the heterozygosity of F1 plus one-half of the mean heterozygosity of the two
      parental populations. The importance of inferring heterozygosity of F2 is
      discussed from evolutionary perspective.

PMID- 8568214
TI  - Vasopressin- and oxytocin-like systems in the chameleon brain.
AB  - The distribution of vasopressin (VP)-like and oxytocin (OX)-like
      immunoreactivities was investigated in the chameleon brain with antisera specific
      for either peptide. VP-like and OX-like neurons are found only in two nuclei: in
      the supraoptic and in the paraventricular nuclei, whereas both peptidergic
      innervations are restricted to some ventral areas, especially to the
      hypothalamus. However, in these areas, OX-like innervation is less dense than the
      VP-like innervation. Even though, no sex differences were noted for the two
      systems, differences are present between the normal female and the preoviposit
      one concerning VP-like system. In the latter female, numerous VPergic-like cell
      bodies occurred in the ependymal layer, making likely direct contact with the
      cerebrospinal fluid (CSF) of the third ventricle. In addition, some VP-like nerve
      fibers seem to be in supraependymal position at the septal wall, probably also in
      contact with CSF.

PMID- 8568215
TI  - Is the length of the calcarine sulcus associated with the size of the human
      visual cortex? A morphometric study with magnetic resonance tomography.
AB  - PURPOSE: To determine whether the length and depth of the calcarine sulcus are
      associated and can be used for estimating the size of the primary visual area
      (area 17) and other regions in MR images of the human occipital lobe. METHODS:
      The length and depth of the calcarine sulcus and the projection areas of the
      mesial surface of the occipital lobe and of the total hemisphere were measured in
      MR images of 23 healthy subjects. RESULTS: A higher variability of the size of
      the projection area of the mesial surface of the occipital lobe compared with
      that of the remaining part of the hemisphere is found. The projection area of the
      mesial cortical surface of the occipital lobe is correlated with the length of
      the calcarine sulcus, but both parameters are not correlated with the depth of
      the calcarine sulcus and, therefore, also not with the size of the part of area
      17 buried in the sulcus. CONCLUSION: The size of area 17 cannot be estimated by
      the length of the calcarine sulcus in MR images. Depth and length of the
      calcarine sulcus grow independently in the human brain. Different degrees of
      folding may cause the variability of architectonic areas.

PMID- 8568216
TI  - Homology in the evolution of the cerebral hemispheres. The case of reptilian
      dorsal ventricular ridge and its possible correspondence with mammalian
      neocortex.
AB  - The present paper reviews some issues related to the evolutionary origin of
      distinct components of the cerebral hemispheres in vertebrates, which entails the
      problem of biological homology between anatomical structures. Considering that
      the term homology is essentially a comparative concept, making emphasis on
      structural correspondences between organs or body parts, I use the term
      evolutionary, or phylogenetic homology to denote a common evolutionary origin of
      two characters. In particular, the controversy of a possible phylogenetic
      homology between reptilian dorsal ventricular ridge (DVR) and parts of mammalian
      neocortex is analyzed in some detail. Although it is likely that DVR is a derived
      character of reptiles while neocortex is a derived character of mammals, the two
      structures might still originate from the same primordial anlage in the common
      ancestor. One main problem in the comparison of telencephalic components between
      reptiles and mammals is that the protrusion of reptilian DVR into the lateral
      ventricle causes a distortion of the topographic relations in the hemisphere. In
      order to determine possible homologues of DVR, it is necessary to establish clear
      cut telencephalic landmarks. Since lateral cortex is similarly localized in
      reptiles and mammals, it is suggested that the embryonic position and timing of
      development of reptilian DVR in relation to lateral cortex may give special
      insight on the phylogenetic origins of the former. If, as implied by the work of
      early authors, DVR arose in evolution through an extension of the embryonic
      period of neuronal proliferation and migration, it may be considered as a genuine
      novelty in brain evolution. It is also proposed that, regardless of whether DVR
      and extrastriate neocortex can or cannot be considered phylogenetic homologues,
      some of the integrative functions performed by them might have a common
      evolutionary origin, that became localized in reptilian DVR and in mammalian
      extrastriate neocortex.

PMID- 8568217
TI  - Effects of maternal adrenalectomy and glucocorticoid administration on the
      development of rat hippocampus.
AB  - Optic and electron microscopic analysis were performed on the hippocampus of
      fetuses of 20 days gestation, from pregnant rats bilaterally adrenalectomized on
      day 1 of gestation (ADX) and control (C), in an attempt to determine the
      incidence of maternal glucocorticoids on morphological parameters in fetal
      development. In addition, we studied 20 day old fetuses from pregnant rats
      betamethasone-injected on days 15, 16 and 17 (BET), and adrenalectomized on day 1
      and betamethasone-injected on days 15, 16 and 17 (ADX + BET). The adrenalectomy
      led to a decreased total cell number and a marked depletion of the dentate gyrus
      of the hippocampus, and also to widespread indifferentiation, both in the
      pyramidal cell layer of the Ammon's horn and the dentate gyrus, as well as a
      decreased cell number in CA3 stratum pyramidale. No differences in cell number
      were found in CA1. So, the ADX effect is in relation to the neurogenic gradient.
      The main effect of the exogenous glucocorticoid treatment was increased
      maturation in relation to the control group. Betamethasone injection in
      adrenalectomized animals prevented the lower degree of maturation of the
      adrenalectomized group but not the impaired cell number. These results show that
      glucocorticoids participate in prenatal hippocampus in control mechanisms of
      cellular division and in maturation.

PMID- 8568218
TI  - Increased expression of NADPH-diaphorase in visual centres after unilateral optic
      nerve transection in the rat.
AB  - The present study shows an increase NADPH-d histochemical staining in the optic
      layers of the superior colliculus, the ventral nucleus of the lateral geniculate
      body and the primary visual cortex in the rat after transection of the
      contralateral optic nerve. The alteration was observed 4-60 days after the
      lesion, with a maximum at 30 days. These results suggest that retinal activity
      has a transneuronal and time-dependent regulatory effect on nitric oxide
      synthesis in denervated or visually deprived visual centres, an increase that may
      play a role in enhancing local blood flow and could be neuroprotective in
      function.

PMID- 8568219
TI  - Anatomical evidence of a retino-thalamo-hippocampal pathway in the pigeon
      (Columba livia).
AB  - The aim of the present study was to demonstrate the existence of a retino-thalamo
      hippocampal pathway in the pigeon and, more specifically, to identify its
      thalamic relay (n. superficialis parvocellularis: SPC). Fluorescence axonal
      tracing techniques were used combining the orthograde axonal transport of RITC
      after its intraocular injection and the retrograde axonal transport of various
      other fluorescent tracers (FB, FG, EB) injected into the hippocampal complex.
      Since the n.SPC has also been shown to project upon the visual Wulst, different
      fluorescent dyes were injected concomitantly into the latter and the hippocampus
      and the distribution of retrograde somatic labeling within the thalamus was
      compared. The injections into both telencephalic target structures resulted in a
      differential pattern of labeling bilaterally within the thalamic dorsolateral
      anterior (DLA) complex and the n.SPC. Moreover, the distributions of both cell
      types overlapped within the n.SPC, although no double-labeling of individual cell
      bodies indicative of collateralized axonal projections was observed. Direct
      retinal projections upon the n.SPC were also demonstrated and terminated within
      the same regions of the nucleus containing relay cells projecting to both the
      hippocampus and the Wulst. The organization of the retino-thalamo-hippocampal
      pathway in birds is similar to that which has been described in other vertebrate
      groups. A common feature is the presence of divergent projections from a dorsal
      thalamic retino-recipient relay nucleus upon both neopallial visual cortical
      areas and the hippocampus (archipallium).

PMID- 8568220
TI  - Some data on connections of neurons of nuclei isthmi of the chicken.
AB  - After PhA-L injection into the tectum opticum of chickens, column-like labelled
      terminal arborizations were found in tectum and also labelled neurons of Ipc and
      Imc in the corresponding sections. The PhA-L labele proved the projection from
      both Imc and Ipc neurons to tectum; their terminal axonarborizations were clearly
      discernible. Column-like terminal arborizations of different sizes were found
      both in PHA-L and Golgi impregnated preparations. GABA immunostaining displayed
      GABA positive neurons in Imc. The EM-Golgi study corroborated that the axon
      terminals of Imc neurons established symmetrical synapses in the tectum. The
      results of the present study support the existence of an inhibitory feedback loop
      from Imc neurons to the tectum.

PMID- 8568221
TI  - Distribution of Bergmann glial somata and processes: implications for function.
AB  - We have used immunocytochemistry for glial fibrillary adidic protein and
      glutamine synthetase to selectively label Bergmann glia in the adult rat
      cerebellum. From measurements of radial, tangential and en face sections we
      provide new data on the distribution and disposition of these glial cells.
      Specifically, Bergmann glia were found to have a mean areal packing density of
      8,269 somata/mm2, their radial processes are packed at a mean density of
      39,000/mm2, and their endfeet at the pial surface have a mean density of
      19,973/mm2. Each Bergmann glial cell ist "responsible" for the equivalent of a
      column of cerebellar cortex having a base of 11 microns x 11 microns, a height of
      170 microns, and a volume of 20,559 microns3. There are 8.1 Bergmann glia for
      each Purkinje cell, and each glial cell ensheaths between 2,142 and 6,358
      Purkinje cell synapses. We use these data to offer insights on the roles of
      Bergmann glia during development and in the adult brain.

PMID- 8568222
TI  - A note on the distribution of dendritic spines.
AB  - Some previously published data concerning the spatial distributions of dendritic
      spines are re-examined. It appears that such distributions are not completely
      random, but show a tendency towards repulsion, that is to say a deficiency of
      short inter-spine distances and an excess of long distances when compared to a
      totally random model. While this lack of total randomness contradicts an
      assumption underlying a previously published technique for estimating total spine
      number, it does not appear to seriously interfere with this technique.

PMID- 8568223
TI  - Differences in the decrease in regenerative capacity of various brain regions of
      Xenopus laevis are related to differences in the undifferentiated cell
      populations.
AB  - The extent of the undifferentiated cell population in normal and regenerating
      brains of larvae and metamorphosed individuals of Xenopus laevis has been
      analyzed by means of an immunocytochemical method and mitotic index
      determinations. Results show that the decrease in regenerative capacity of the
      brain during larval development and after metamorphosis is in relation with the
      gradual reduction of the population of undifferentiated cells and that the
      different regenerative capacities of the various brain districts are related to
      quantitative and qualitative differences in this cell population. While in the
      early larval stages the cell population formed of actively cycling cells is very
      large and widespread, in late larval stages and after metamorphosis these cells
      localize in some encephalic areas (matrix zones). This localization occurs later
      in the telencephalon than in the rhombencephalon and in mesencephalon. The less
      conspicuous decrement in the regenerative capacity of the telencephalon than of
      other encephalic districts of froglets, particularly the mesencephalon, is
      related to the presence of a larger number of actively cycling cells together
      with a rather large number of undifferentiated cells which are in a temporary
      quiescent state from which they may re-enter the actively cycling state in
      response to proliferation promoting factors.

PMID- 8568224
TI  - Surface complexity of human neocortical astrocytic cells: changes with
      development, aging, and dementia.
AB  - Astrocytes from area 11 of the human neocortex were Golgi-impregnated. The
      material was taken from four human subjects, (1) a neonate without obvious CNS
      damage, (2) a middle-aged adult serving as control, (3) an aged individual
      without apparent mental disturbances, and (4) an aged patient with dementia.
      Camera-lucida drawings of 7 to 26 astrocytic cells from each donor were digitized
      into a personal computer, and analyzed for their fractal dimension D which is an
      objective and quantitative measure of the complexity of the cell's borders. Both
      radial and multipolar astrocytes from neonatal cortex showed a comparatively low
      fractal dimension (D approximately 1.39), that is, low surface complexity. Adult
      ("control") astrocytes were characterized by a high fractal dimension (D = 1.57),
      corresponding to their large surface complexity. Astrocytes from the aged subject
      showed a somewhat smaller fractal dimension (D = 1.51) and, thus, surface
      complexity; this difference was however not highly significant. In contrast,
      astrocytes from the subject with dementia showed a significant reduction in
      surface complexity (D = 1.47). Parallel changes were observed in the brain volume
      compartment occupied by the process of individual astrocytes. These data suggest
      that formation and maintenance of astrocytic processes and/or side branches
      correlate positively with the degree of information processing within their
      neuronal environment.

PMID- 8568225
TI  - Topographical organization of NADPH-diaphorase positive neurons and fibres in
      dorsal ponto-mesencephalic tegmentum in the rat brain.
AB  - 20 complete series of the rat brain, stained with cresylviolet or with the NADPH
      diaphorase positive neurons demonstration method were used to compare the
      topographical organization of the borders of the dorsal mesopontine tegmental
      nuclei (latero-dorsal tegmental nucleus, dorsal and ventral tegmental nuclei of
      Gudden, dorsal raphe nucleus and substantia grisea centralis pontis) and to
      describe in detail NADPH-d positive cells and fibres in this area. We have found
      that topography of the cells and the borders of the nuclei were similar by the
      both methods, but NADPH-d histochemistry has shown the extension of NADPH-d
      positive cells to neighbouring structures and we would divide some nuclei into
      independent parts (e.g., pars medialis, ventralis and rostralis of the
      laterodorsal tegmental nucleus). We discussed the possibility of the projection
      and configuration of NADPH-d positive fibres running from the mesopontine
      tegmentum to the diencephalon.

PMID- 8568226
TI  - Medullary and gangliar regeneration after unilateral removal of a segment of
      spinal cord of the trunk and corresponding ganglion in adult newts.
AB  - Regeneration of the spinal cord, segmental nerves and sensory ganglia takes place
      after tail amputation in the newt. Many histological and immunocytochemical
      observations provide evidence that the ependymal tube is the source not only of
      new neurons and glial cells in the spinal cord, but also of some cells that go on
      to participate in the formation of the spinal ganglia of the regenerating tail.
      In previous experiments involving the removal of the spinal ganglia of the trunk,
      no regeneration was observed and it is thought that the trunk region differs from
      the tail region with regard to the ability to regenerate sensory ganglia.
      However, in these experiments the spinal cord of the trunk was not damaged. In
      the present work involving adult newts (Triturus carnifex Laur.), unilateral
      ablation of a segment of the spinal cord of the trunk in addition to removal of a
      corresponding spinal ganglion was performed. In these experimental conditions,
      regeneration of a rudimentary spinal ganglion near the regenerated side of the
      spinal cord segment was observed in several cases. Histological observations
      carried out 2, 4, 6 and 13 months after the operation support the view that some
      cells migrating from the lateroventral part of the regenerating side of the
      spinal cord via the developing ventral root could participate in the formation of
      the rudimentary spinal ganglion.

PMID- 8568227
TI  - A light and electron microscopic study of HLA-DR positive cells in the human
      cerebral cortex and subcortical white matter.
AB  - Specimens of histologically normal human cerebral cortex and subcortical white
      matter were obtained during neurosurgical operations and studied by electron
      microscopy and immunocytochemistry using an antibody against HLA-DR. Greater
      numbers of labelled cells were present in the white matter than in the overlying
      cortex. The labelled cells consisted of ramified microglia and perivascular
      cells. Microglia were often found just outside the walls of small blood vessels,
      but perivascular cells were actually enclosed by two leaflets of basement
      membrane in the walls of capillaries, arterioles and venules up to 100 microns in
      luminal diameter. Labelled microglial processes were often seen enclosing
      neuronal processes in the cortex and myelinated and unmyelinated axons in the
      white matter. The enclosed processes appeared healthy, and without features of
      degenerating neurons. These observations are consistent with a previous
      suggestion that microglia continually modify the processes of central nervous
      system neurons by a process of phagocytosis. An intact blood-brain barrier is
      likely to be of great importance in preventing antigen presentation of the
      processed neuronal, and perhaps even oligodendrocytic, antigenic peptide
      fragments to circulating lymphocytes.

PMID- 8568228
TI  - Regional differences in the blood-brain-barrier of the subfornical organs of rats
      and ducks (Anas platyrhynchos).
AB  - Recently published electrophysiological data investigated the effect of blood
      borne and brain intrinsic substances on the activity of neurons in the duck
      subfornical organ (SFO). This study defines histologically the region in the duck
      SFO, where blood borne substances can possibly influence neuronal activity.
      Intravenous injection of Evans blue, a dye which labels brain structures devoid
      of a blood brain barrier (BBB), resulted in diffuse labelling of the duck SFO
      from the anterior commissure to the end of the organ in rostrocaudal extension.
      In addition, specifically labelled neurons could be observed just rostral to the
      diffuse Evans blue labelling and in an area dorsomedial to the large central
      blood vessel. The majority of the somata of these heavily stained neurons were
      located inside the BBB, whereas in the areas with diffuse Evans blue labelling,
      thus being outside the BBB, labelled cells were rarely observed. Intravenous
      injection of Evans blue in rats resulted similarly in diffuse labelling of the
      parenchyma of the medial and caudal part of the SFO, with only a few, but heavily
      stained cells with fusiform somata. The rostral region of the rat SFO, which is
      known to have a functional BBB, shows hardly any diffuse labelling, but there the
      majority of neurons show strong Evans blue fluorescence. It is concluded that the
      heavily labelled somata inside the BBB have axonal or dendritic projections to
      BBB-free areas, where they can take up the dye. This study gives a functional
      description of the extension of the SFO areas without a BBB of rats and ducks. It
      is concluded that blood borne agents can affect those SFO neurons which have
      their somata located outside the BBB as well as those located inside the BBB
      which have terminals projecting to BBB free regions.

PMID- 8568229
TI  - Anergy as a mechanism of peripheral T cell tolerance.

PMID- 8568230
TI  - Acquisition of surface IgD fails to protect from tolerance-induction. Both
      surface IgM- and surface IgD-mediated signals induce apoptosis of immature murine
      B lymphocytes.
AB  - While mature splenic B cells are surface (s)IgM+ and sIgD+, immature, tolerance
      susceptible B cells express sIgM and varying levels of sIgD. Differential
      expression of sIgD on tolerance-susceptible and resistant B cells suggests that
      sIgM and sIgD may transmit qualitatively different signals. Alternatively,
      tolerance sensitivity may be associated with intrinsic differences in sIg
      signaling, regardless of the isotype engaged. Here, we have exploited a stage of
      B cell development at which immature, tolerance-sensitive B cells co-express sIgD
      and sIgM. Using these immature stage B cells to evaluate isotypic differences in
      the ability to induce activation and deletion, we have found that neither
      ligation of sIgD nor sIgM is capable of inducing proliferation. Moreover, in
      contrast to mature B cells, both sIgD and sIgM induce apoptosis by immature stage
      B cells. Importantly, cross-linking sIgD does not protect immature B cells from
      sIgM-induced apoptosis. Thus, the differences in tolerance susceptibility of
      immature and mature B cells must be due to intrinsic developmental rather than
      isotypic differences in Ag receptor signal transduction.

PMID- 8568231
TI  - IL-7 differentially modulates the expression of IFN-gamma and IL-4 in activated
      human T lymphocytes by transcriptional and post-transcriptional mechanisms.
AB  - We investigated the role of IL-7 on the expression of IFN-gamma and IL-4 in human
      T lymphocytes. IL-7 alone did not induce IFN-gamma or IL-4 mRNA. However, IL-7
      dose-dependently up-regulates the anti-CD3- or anti-CD3/anti-CD28-induced IFN
      gamma and IL-4 mRNA expression. Used at an optimal concentration, IL-7 (5 ng/ml)
      increased the accumulation of IFN-gamma (eightfold) and IL-4 (2.5-fold) mRNAs,
      which could not be blocked by anti-IL-12 treatment. The enhanced IFN-gamma mRNA
      accumulation was observed within 3 to 6 h, without altering the pattern of the
      kinetics. However, longer exposure (> 12 h) did not result in different IFN-gamma
      expression for anti-CD3/anti-CD28 vs anti-CD3/anti-CD28 plus IL-7-stimulated T
      lymphocytes. mRNA stability studies revealed that IL-7 stabilizes both IFN-gamma
      and IL-4 mRNA transcripts: 40 and 60 min in anti-CD3/anti-CD28-stimulated T cells
      vs 120 and 90 min in T cells costimulated with anti-CD3/anti-CD28 plus IL-7.
      Nuclear run-on assays revealed that the transcription rate of the IFN-gamma gene
      increased approximately twofold in the presence of IL-7, without affecting the
      transcription rate of the IL-4 gene. The IL-7-mediated IFN-gamma up-regulation
      could not be inhibited by cycloheximide treatment, in contrast to IL-4 gene
      expression. However, the promotive effect of IL-7 on IFN-gamma and IL-4 gene
      expression could be blocked by genistein and cyclosporin A. Finally, it was
      demonstrated that the effect of IL-7 on IFN-gamma mRNA accumulation was also
      reflected at the protein level. In summary, these data demonstrate that IL-7
      preferentially up-regulates IFN-gamma expression in activated T lymphocytes,
      which is accomplished at transcriptional and post-transcriptional levels.

PMID- 8568232
TI  - Interaction of IL-15 with the shared IL-2 receptor beta and gamma c subunits. The
      IL-15/beta/gamma c receptor-ligand complex is less stable than the IL
      2/beta/gamma c receptor-ligand complex.
AB  - This study was designed to compare the interactions of IL-2 and IL-15 with the IL
      2R beta and IL-2R gamma c subunits, as differences in receptor interactions
      between IL-2 and IL-15 might contribute to the functional differences between
      these two cytokines. The results suggest the existence of a human IL-15R alpha
      subunit, although physical evidence of this molecule was not obtained.
      Proliferation of anti-CD3 (OKT3)-stimulated human PBL was compared for
      responsiveness to IL-2, IL-15, and F42K, and IL-2 mutant that does not bind the
      IL-2R alpha chain. F42K was more potent than IL-15 in activating a dose-dependent
      response. This fact, along with Scatchard binding analyses of IL-15 on OKT3
      blasts and YT cells revealing both high and intermediate affinity receptors,
      supports the existence of IL-15R alpha on these cells. Additional
      characterization of the IL-15R utilized covalent cross-linking to affinity label
      IL-2R and IL-15R on YT cells and OKT3 blasts. Consistent with previously reported
      functional data, IL-2R alpha was not co-precipitated from the [125I]IL-15
      receptor-ligand complex, demonstrating that IL-15 does not interact physically
      with the IL-2R alpha subunit. While IL-2R alpha did co-precipitate with IL-2R
      beta and IL-2R gamma c in the presence of IL-2, IL-15R alpha did not co
      precipitate with the IL-2R beta/gamma c complex. Finally, YT cells equilibrated
      with IL-2 and then precipitated through IL-2R beta showed that IL-2R beta and IL
      2R gamma c co-precipitate in a 1:1 ratio, while only IL-2R beta was found in the
      immunoprecipitates of YT cells equilibrated with IL-15. This indicates that IL-15
      creates a less stable bridge between the IL-2R beta and IL-2R gamma c chains than
      does IL-2 on YT cells. This result was identical for both surface-iodinated YT
      cells and immunoprecipitates that were probed for IL-2R beta and IL-2R gamma c on
      Western blots.

PMID- 8568233
TI  - Characterization of adenosine deaminase binding to human CD26 on T cells and its
      biologic role in immune response.
AB  - CD26, a T cell activation Ag, also known as dipeptidyl peptidase IV, is directly
      associated with adenosine deaminase (ADA) on the surface of T cells and T cell
      lines. In the present study, we examined both the binding of ADA and CD26 and the
      functional consequences of this interaction. We found that ADA was associated
      with CD26 on T cell lines lacking either ADA or dipeptidyl peptidase IV enzymatic
      activity, indicating that the association between dipeptidyl peptidase IV and ADA
      did not require enzymatic activity. Moreover, using immunoelectron microscopy, we
      demonstrated that CD26 and ADA co-localized on the cell surface, but not inside
      cells, suggesting that CD26 did not transport ADA to the surface. In keeping with
      this observation, we showed that human CD26-transfected murine pre-B cell lines
      lacking human ADA acquired ADA from an extracellular source. More importantly,
      adenosine in the absence of cell surface ADA inhibited T cell proliferation and
      IL-2 production induced by various stimuli. On the other hand, cells expressing
      ADA and CD26 on the surface were much more resistant to the inhibitory effect of
      adenosine. These data suggest that ADA on the cell surface is involved in an
      important immunoregulatory mechanism by which released ADA binds to cell surface
      CD26, and this complex is capable of reducing the local concentration of
      adenosine.

PMID- 8568234
TI  - Early signal transduction by the receptor to the chemokine monocyte chemotactic
      protein-1 in a murine T cell hybrid.
AB  - Members of the C-C family of chemotactic cytokines promote chemotaxis and
      adhesion of leukocytes. In this study, we have identified a murine T cell hybrid
      that expresses receptors to the chemotactic cytokine monocyte chemotactic protein
      1 (MCP-1). This cell line was used to examine MCP-1 receptor-mediated signal
      transduction events in a homologous system in the absence of interference with
      other receptors. Our results show that in the 3B4 M1.9 T cell hybrid, MCP-1
      receptors mediate intracellular calcium mobilization and extracellular calcium
      import without detectable increases in total water-soluble inositol phosphates.
      In addition, MCP-1 regulates the tyrosine phosphorylation of specific substrates
      at 42 and 44 kDa and induces mobility shift of p42/44 mitogen-activated protein
      kinases. MCP-1-mediated calcium responses, tyrosine phosphorylation, and the
      electrophoretic mobility shift of p42/44 mitogen-activated protein kinases can be
      inhibited by pretreatment of cells with pertussis toxin, indicating a role for Gi
      like G proteins in coupling the MCP-1R to signal transduction.

PMID- 8568235
TI  - Immature T cells in peripheral lymphoid organs of recombinase-activating gene-1/
      2-deficient mice. Thymus dependence and responsiveness to anti-CD3 epsilon
      antibody.
AB  - Thymocytes of mice deficient in the recombinase-activating gene (RAG)-1 or RAG-2
      cannot express and receive signals through the pre-TCR. As a result, thymocyte
      development in these mice terminates at the CD4/8 double negative (DN), IL-2R
      alpha-positive stage. Nevertheless, RAG-deficient DN thymocytes express
      functional CD3 complexes and can therefore be induced by anti-CD3 epsilon mAb to
      mature to the CD4+8+ double positive stage. In the present paper we demonstrate
      that the peripheral lymphoid organs (lymph nodes, spleen) and peripheral blood of
      RAG-deficient mice harbor an immature T cell population which, similar to RAG
      deficient DN thymocytes, contains high levels of cytoplasmic CD3 epsilon and
      responds to anti-CD3 epsilon mAb in vivo. With respect to surface phenotype
      (Thy1.2+, PgP-1+, HSA+, Fc gamma RII/III-, IL-2R-alpha-, c-kit-), these cells are
      similar to intermediate stage RAG-deficient DN thymocytes. Moreover, they express
      mRNA for pre-TCR-alpha and for the nondeleted RAG. Following injection of anti
      CD3 epsilon mAb, these cells proliferate, down-regulate heat stable Ag and PgP-1,
      and partially differentiate to CD4+ and CD8+ double positive and single positive
      cells. The induced population displays a mixed phenotype, between that of
      immature thymocytes and lymph node T cells in normal mice. Induction is
      successful in thymectomized RAG-deficient mice, suggesting that it occurs in the
      periphery. However, after thymectomy, inducible cells disappear with an
      approximate half-life of 10 to 14 days. We suggest that DN thymocytes can
      emigrate and repopulate peripheral lymphoid organs of RAG-deficient mice. These
      cells respond to CD3 signaling by aberrant maturation, possibly due to the
      inappropriate microenvironment of peripheral lymphoid organs.

PMID- 8568236
TI  - Physical and functional interactions of protein tyrosine kinases, p59fyn and ZAP
      70, in T cell signaling.
AB  - The src family protein tyrosine kinases participate in signaling through cell
      surface receptors that lack intrinsic tyrosine kinase domains. One of the src
      family kinases, p59fyn (Fyn), plays an important role in the TCR-mediated
      signaling. Here we report that Fyn becomes associated with the zeta-associated
      tyrosine kinase, ZAP-70, in a T cell hybridoma upon stimulation. The association
      was transient; it occurred as early as 10 s after stimulation and disappeared
      after 10 min. The two proteins were also associated with each other when
      coexpressed in COS cells. Coexpression of the zeta-chain was not required for
      their interaction. Mutational analysis of Fyn and ZAP-70 revealed that their
      kinase activities were relevant to the association. Deletion of both the SH2 and
      SH3 domains of Fyn resulted in the decrease of the association with ZAP-70.
      Consistently, Fyn-SH2 and Fyn-SH3 fused to glutathione S-transferase were able to
      bind to ZAP-70. These data suggest that multiple sites of Fyn and ZAP-70 are
      involved in the association. Furthermore, coexpression of the wild-type of both
      kinases in COS cells enhanced tyrosine phosphorylation of the helix-turn-helix
      containing protein, HS1. HS1 was also tyrosine phosphorylated upon TCR
      stimulation. Thus, we propose that Fyn phosphorylates and activates ZAP-70 and
      that both kinases cooperate in TCR signaling.

PMID- 8568237
TI  - Stat1 implication in the immune response to superantigens in vivo.
AB  - We analyzed the activation and changes in the protein level of STAT1 as a
      consequence of in vivo treatment with superantigens. Ninety minutes after i.p.
      injection of the staphylococcal enterotoxin B (SEB), a complex containing STAT1
      that was able to specifically bind to DNA containing GAS-like sequences was
      activated in mouse splenocytes. This complex had the same characteristics as that
      induced by IFN-gamma in several in vitro systems. Activation of the complex was
      inhibited by cyclosporin A, and Abs against IFN-gamma severely decreased the
      amount of complex detected. When splenocytes were analyzed 24 h after SEB
      treatment, a high increase in the amount of the STAT1 isoforms, STAT91 and
      STAT84, was observed by Western analysis, but binding to GAS-like sequences was
      clearly decreased when compared with analysis at 90 min. Nevertheless, when SEB
      was injected a second time 24 h after the first injection, the binding of STAT1
      to GAS-like sequences had risen again. This approach corroborates the implication
      of IFN-gamma in the response to superantigens in vivo and shows the relevance of
      analysis of transcription factors in defining the molecular events involved in
      the immune response.

PMID- 8568238
TI  - CD30 expression does not discriminate between human Th1- and Th2-type T cells.
AB  - CD30 is a member of the TNF receptor superfamily that is commonly used as a
      marker for Hodgkin and Reed-Sternberg cells in Hodgkin's disease. More recently,
      it has been proposed that CD30 is preferentially up-regulated on Th2-type human T
      cells. We analyzed regulation of CD30 expression on both peripheral blood T cells
      and T cell clones. In short-term culture, CD30 expression could be induced on T
      cells by Ags that elicit Th2-type responses (Schistosoma haematobium, adult worm
      Ag, and Toxocaria canis, excretory/secretory Ag) and Th0-type responses (tetanus
      toxoid), as well as Th1-type responses (tuberculin purified protein derivative).
      Moreover, simultaneous measurement of membrane phenotype and cytokine production
      showed that CD30-expressing cells can produce IFN-gamma. Finally, within panels
      of randomly generated as well as Ag-specific T cell clones, CD30 expression was
      found on Th0-, Th2-, and Th1-type clones. We conclude that induction of CD30 on
      activated T cells is not related to differentiation in Th0-, Th1-, or Th2-type
      cells.

PMID- 8568239
TI  - Human B cells express IL-5 receptor messenger ribonucleic acid and respond to IL
      5 with enhanced IgM production after mitogenic stimulation with Moraxella
      catarrhalis.
AB  - The potential for IL-5 to regulate human B cells is controversial despite its
      well established role as a regulatory factor for murine B cells. We hypothesized
      that the mechanism by which human B cells were stimulated would, as with murine B
      cells, determine their potential to respond to IL-5. Since Staphylococcus aureus
      Cowan strain I (SAC) and Moraxella catarrhalis (MCat) stimulate human B cells by
      distinct interactions with cell-surface Ig, we compared their potential to induce
      an IL-5-responsive state by human B cells purified to homogeneity. Neither SAC
      alone nor SAC plus IL-5 stimulated Ig production, although microgram quantities
      of IgM were produced with SAC plus IL-2. In contrast, MCat induced microgram
      quantities of IgM by B cells in the absence of exogenous cytokines, and IL-5
      significantly increased IgM production over twofold in the majority of donors.
      Synergism of IL-5 and IL-2 was detected using suboptimal concentrations of IL-2
      with MCat-, but not SAC-, stimulated B cells. Donor B cells unresponsive to IL-5
      when stimulated with MCat, became IL-5 responsive in the presence of IL-2. Since
      message for the IL-5R alpha, IL-5R beta, and soluble IL-5R alpha chains was
      detected in freshly isolated B cells, we further investigated whether IL-5
      responsiveness to MCat, but not SAC, was due to their differential regulation of
      IL-5R mRNA. Surprisingly, stimulation by either MCat or SAC, without or with IL
      2, increased both IL-5R alpha and IL-5R beta mRNA and decreased soluble IL-5R
      alpha mRNA. These studies demonstrate that, as with murine B cells, human B cells
      express message for IL-5R but can respond to IL-5 only if appropriately
      stimulated to undergo terminal differentiation.

PMID- 8568240
TI  - IL-12 synthesis by human Langerhans cells.
AB  - IL-12 is a 70-kDa heterodimeric cytokine composed of a p35 chain and p40 chain.
      This cytokine exerts a powerful positive regulatory influence on the development
      of Th1 helper T-cell immune responses and is a potent inducer of IFN-gamma
      production and cytotoxic T cell differentiation and function. Because epidermal
      Langerhans cells (LC) are important members of the dendritic APC lineage family
      critical for initiating cell mediated immune responses, we examined LC for their
      ability to produce IL-12. Epidermal cell (EC) suspensions obtained from
      volunteers were enriched for, or depleted of, Langerhans cells (CD1a+ EC).
      Enriched populations contained > 90% CD1a+ cells, whereas depleted populations
      contained < 1% CD1a+ cells. As assessed by reverse transcription-PCR
      amplification, IL-12 p40 mRNA was constitutively expressed in LC RNA extracted
      immediately following keratome harvest, and increased spontaneously after
      overnight incubation. Radioimmunoassay (RIA) of IL-12 p40 protein on supernatants
      revealed IL-12 release by CD1a-enriched fractions of epidermal cells. Ab specific
      for p40 clearly demonstrated IL-12 in epidermal LC by flow cytometry. A bioassay
      for the functional IL-12 heterodimer (p70) indicated that LC could produce IL-12
      biologic activity, which was neutralized by anti-IL-12 Ab. These results indicate
      that epidermal LC, in particular cultured LC maturing into dendritic cells,
      express IL-12 p40 mRNA, as well as p40 and functional p70 protein, and suggest
      that this is one mechanism behind the high potency of dendritic APCs, such as LC,
      to initiate Th1 type immune responses under appropriate conditions.

PMID- 8568241
TI  - Class II MHC antigen (Ia)-bearing dendritic cells in the epithelium of the rat
      intestine.
AB  - Many tissues are found to contain populations of cells with an unusual dendritic
      shape, high levels of surface expression of MHC class II (Ia) gene products, and
      strong accessory function for the stimulation of specific clones of quiescent T
      lymphocytes. Dendritic cells (DC) represent major population of "professional"
      APC in various lymphoid and nonlymphoid tissues, distinct from cells of the
      monocyte/macrophage lineage. Among the best characterized nonlymphoid dendritic
      cells are epidermal Langerhans cells, but it has been shown that interstitium and
      epithelium of other organs also contain irregularly shaped, strongly MHC class II
      positive cells. In recent years, DC have been localized to alveolar septa in the
      lung, as well as within and just beneath airway epithelium, comprising a tightly
      meshed network that is reminiscent of epidermal Langerhans cells. In the
      gastrointestinal tract, conventional immunohistochemical analysis of mucosal
      class II MHC (Ia) staining reveals a morphologically heterogeneous pattern of
      staining in the lamina propria. DC that exhibit strong Ag-presenting activity in
      vitro have been extracted from enzymatic digests of colonic mucosa, but no
      previous reports of MHC class II-positive cells with pleiomorphic morphology have
      been recorded within the epithelium of the intestine. Employing a novel
      combination of nonconventional section planes, pre-embedding fixation, and
      immunohistochemical techniques, we now demonstrate Ia staining of cells with
      classical DC morphology within the epithelium of the intestine in normal specific
      pathogen-free rats. Our investigation suggests that cells with the morphologic
      and phenotypical characteristics of DC are present within the mucosal epithelium
      of the rat jejunum and colon, comprising a significant organized network. The
      number of DC within epithelium of the colon was 117 +/- 20 per 10-microns-thick
      cross-section. These findings have important theoretical implications for
      research on Ag processing and T cell activation in the context of allergic and
      infectious diseases in the gastrointestinal tract.

PMID- 8568242
TI  - Role of the TCR binding region of the HLA class I alpha 2 domain in regulation of
      cell adhesion and proliferation.
AB  - In addition to Ag presentation for T cell surveillance, MHC molecules have been
      implicated in mediating regulatory signals. We have assessed biologic responses
      following engagement of the TCR accessible region of the HLA class I alpha 2
      domain. mAbs directed to this domain specifically induced cell aggregation of
      normal hematopoietic and leukemic cells. The functional consequences were unique
      since other mAbs reactive with HLA class I residues outside the TCR binding
      domain did not induce cell aggregation. The adhesion response required ATP, mRNA,
      protein, and actin synthesis and did not depend on LFA-1/ICAM interactions. Cell
      aggregation was also induced when all but four of the intracytoplasmic residues
      of the class I molecule were deleted, indicating that transduction of signals
      leading to cell adhesion does not require this portion of the molecule. mAbs
      directed to HLA class I alpha 2 amino acid residues within the TCR binding domain
      were also able to inhibit proliferation of normal mitogen-stimulated T cells.
      Growth inhibition correlated with down-regulated expression of CD25, CD28, and
      CD95, suggesting that reduced transduction of costimulatory signals is involved.
      Although HLA class I signals inducing cell aggregation required engagement of
      positions within the TCR binding region, growth inhibitory signals could be
      generated through positions both within and adjacent to this domain. Taken
      together, engagement of specific positions within the TCR binding domain of the
      class I alpha 2 helix results in active cellular responses. Thus, this region may
      be directly involved in signal transduction following CTL recognition of target
      cells.

PMID- 8568243
TI  - T cell activation is regulated by voltage-dependent and calcium-activated
      potassium channels.
AB  - Membrane potential (Vm) is tightly controlled in T cells through the regulated
      flux of ions across the plasma membrane. To investigate the functional role of
      voltage-dependent (Kv) and calcium-activated (KCa) potassium channels in T cell
      activation, we compared the effects of two K+ channel blockers, namely kaliotoxin
      (KTX) and charybdotoxin (CHTX), on Vm, calcium influx, and cell proliferation.
      KTX potently inhibited Kv (ID50 = 3 nM) but not KCa (ID50 = 5 microM) currents in
      T cells. Resting T cells exposed to KTX (300 nM) depolarized from -56 mV to -50
      mV. KTX had no effect on the transient membrane hyperpolarization that
      characteristically follows receptor-mediated T cell stimulation. However, T cells
      stimulated in the presence of KTX subsequently depolarized to -40 mV. KTX also
      reduced the steady state intracellular free calcium concentration ([Ca2+]i) in
      stimulated cells by 19% and inhibited T cell proliferation by 35%. CHTX potently
      inhibited both Kv and KCa currents (ID50 = approximately 1 nM). CHTX (300 nM)
      depolarized resting T cells to -48 mV, equivalent to the effect observed for KTX.
      In stimulated T cells, 300 nM CHTX completely blocked the induced
      hyperpolarization and subsequently depolarized the cells to -21 mV. These effects
      were associated with a 45% reduction in peak [Ca2+]i, a 60% decrease in steady
      state [Ca2+]i, and 63% inhibition of T cell proliferation. These results suggest
      that both Kv and KCa conductances contribute to the underlying mechanisms of T
      cell activation.

PMID- 8568244
TI  - Postnatal development of T cells in dogs with X-linked severe combined
      immunodeficiency.
AB  - X-linked severe combined immunodeficiency disease (XSCID) in both humans and dogs
      results from mutations in the common gamma-chain, gamma c, which is a common
      component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15. Although human
      and canine XSCID share similar features, such as a failure to thrive,
      hypogammaglobulinemia, an absent T cell mitogenic response, and thymic dysplasia,
      near normal percentages of T cells are observed in some affected dogs, whereas
      XSCID boys have few, if any, circulating T cells. In this study, PBL were
      analyzed by flow cytometry beginning shortly after birth until 9 wk of age. XSCID
      dogs < 3 wk of age had an elevated number of B cells and were nearly devoid of T
      cells, phenotypically resembling most human XSCID patients. At 5 wk of age,
      however, T cells appeared in approximately one-half of the XSCID dogs, although
      the absolute number of T cells was one-third of normal in these dogs. While the
      percentage of CD45RA+ T cells in normal dogs gradually decreased with age from >
      90% in neonates to < 40% by 3 to 5 yr of age, in XSCID dogs a rapid decline in
      the percentage of CD45RA+ T cells was observed, resulting in < 10% CD45RA+ T
      cells by 7 to 9 wk of age. Maternal engraftment was not detected in any of the
      XSCID dogs by using a sensitive PCR assay. The appearance of nonmaternally
      derived T cells in XSCID dogs that undergo a rapid switch from CD45RA+ to CD45RA-
      suggests that limited thymic emigration and peripheral expansion of T cells can
      occur in the absence of a functional gamma c.

PMID- 8568245
TI  - Cell-mediated cytotoxicity results from, but may not be critical for, primary
      allograft rejection.
AB  - Tumor cells insensitive to lysis through the Fas and TNF pathways were injected
      either subcutaneously or into the peritoneal cavities of allogeneic perforin-less
      (P0) and perforin wild-type (P2) mice. In three of four cases, the tumors were
      rejected equally rapidly in both strains of mice. Rejection was accompanied by
      vigorous in vitro cytotoxicity in P2, but not in P0 mice. The rapid clearance of
      allografted cells in mice where all three known cytolytic pathways are seriously
      compromised raises important questions about the involvement of cell-mediated
      cytotoxicity, as defined by current assay techniques, in primary allograft
      rejection.

PMID- 8568246
TI  - Roles of IFN-gamma and IFN-alpha in IL-12-induced T helper cell-1 development.
AB  - IL-12 and IL-4 direct T cell development toward Th1 and Th2 phenotypes,
      respectively. While IFN-gamma and IFN-alpha have been reported to regulate Th1
      development as well, the mechanism and cellular locus of their effects are
      unclear. In this study, we use a TCR-transgenic system to examine the actions of
      these cytokines on CD4+ T cell phenotype development. We find that neither IFN
      gamma nor IFN-alpha can induce Th1 development alone. However, IFN-gamma can
      significantly augment IL-12 priming for subsequent IFN-gamma production by T
      cells. Interestingly, lymphocyte endothelial cell adhesion molecule-1bright
      (naive) T cells require IFN-gamma during primary activation for maximal IL-12
      induced Th1 development, whereas lymphocyte endothelial cell adhesion molecule
      1dull (memory) T cells do not. IFN-alpha only partially substitutes for IFN-gamma
      in promoting IL-12-induced Th1 development. When the endogenous IFN-gamma present
      in primary T cell cultures is neutralized, IFN-alpha treatment augments IL-12
      induced effects on inhibition of subsequent IL-4 production, but fails to
      significantly enhance IL-12 priming for subsequent IFN-gamma production. Thus,
      our data suggest that IFN-gamma provides a direct costimulatory signal to T cells
      to up-regulate IL-12-induced Th1 development and may operate by inducing IL-12
      responsiveness in naive T cells.

PMID- 8568247
TI  - A zinc finger protein that represses transcription of the human MHC class II
      gene, DPA.
AB  - The proximal promoters of all MHC class II genes contain a sequence element, the
      19-bp X box, that is conserved in both sequence and position. Extensive analysis
      using a wide variety of approaches has demonstrated that the integrity of the X
      box is essential for transcription initiation from all class II genes studied.
      However, the X box is now recognized to contain two subregions, termed X1 and X2.
      Radiolabeled oligonucleotides corresponding to the X2 box of the MHC class II
      genes DPA and DQB were used to screen B cell and T cell expression libraries. A
      novel cDNA, termed XBR (X box repressor), encoding a putative zinc finger protein
      that binds specifically to the DPA X2 box was isolated from a human T cell line.
      The XBR gene encodes a 7-kb message that is ubiquitously transcribed, although at
      higher levels in tissues of the lymphocytic compartment. Southern blots indicate
      that this gene is single copy in primates and contains regions that are highly
      divergent in other species. Overexpression of XBR in a B cell line resulted in a
      dramatic reduction of transcription from a reporter gene construct driven by the
      DPA promoter, but not from similar constructs with mutations in the X2 box.
      Similarly, overexpression of XBR reduced induction of reporter gene activity
      driven from the DPA promoter in HeLa cells treated with IFN-gamma. XBR may,
      therefore, mediate transcriptional repression, thus preventing inappropriate MHC
      class II expression. XBR function may in part explain the dominant trans-acting
      repression of MHC class II expression reported in cell fusion experiments.

PMID- 8568248
TI  - IL-12 is essential for resistance against Yersinia enterocolitica by triggering
      IFN-gamma production in NK cells and CD4+ T cells.
AB  - Although Yersinia enterocolitica is extracellularly located in infected tissues,
      a specific T cell response is required to overcome infection. Recent work
      implicated that in contrast to Yersinia-susceptible BALB/c mice, C57BL/6 mice are
      Yersinia resistant due to the rapid development of a Yersinia-specific Th1 T cell
      response. This study focused on the role of IL-12 in Y. enterocolitica infections
      in both mouse strains. We found that C57BL/6 and BALB/c mice produced comparable
      quantities of IL-12 mRNA after Y. enterocolitica infection. Likewise, Yersinia
      infected bone marrow macrophages from both mouse strains produced equal
      quantities of IL-12. Administration of neutralizing anti-IL-12 Abs abrogated
      resistance against yersiniae in either strain. In addition, administration of rIL
      12 rendered BALB/c mice resistant to yersiniae, while this treatment was toxic to
      C57BL/6 mice. IL-12-mediated protection was partially dependent on IFN-gamma.
      Spleen cells from both strains of mice produced Yersinia-triggered IFN-gamma in
      an IL-12-dependent manner, although those from BALB/c mice produced 10-fold
      lesser quantities. Administration of rIL-12 in vivo increased Yersinia-induced
      IFN-gamma production by BALB/c spleen cells in vitro, but decreased IFN-gamma
      production by spleen cells from C57BL/6 mice. IL-10 was antagonistic to IL-12
      only in BALB/c mice and inhibited Yersinia-triggered IFN-gamma production. In
      vivo depletion experiments revealed that IL-12 accounts for Yersinia-induced IFN
      gamma production by both NK cells and CD4+ T cells, the latter of which are an
      essential source of IFN-gamma r while NK cell-derived IFN-gamma production can be
      compensated by other cells. In contrast to that in the spleen, IL-12 plays a
      minor role in protection against yersiniae in Peyer's patches after orogastric
      infection. In summary, our data suggest that IL-12 is rapidly induced by Y.
      enterocolitica infection and required for IFN-gamma production by NK cells as
      well by CD4+ T cells. Although BALB/c and C57BL/6 mice produced comparable
      quantities of IL-12, IFN-gamma production, and thus resistance to yersiniae, can
      be increased by exogenous IL-12 only in BALB/c, not in C57BL/6, mice.

PMID- 8568250
TI  - Contribution of nitric oxide to the host parasite equilibrium in toxoplasmosis.
AB  - We studied the effect of nitric oxide (NO) production on the evolution of
      toxoplasmosis in C57BL/6 mice. Infection was induced by i.p. injection of
      Toxoplasma gondii strain ME49. NO synthesis was inhibited by treatment with
      aminoguanidine, a structural analogue of L-arginine. The severity of infection
      was evaluated by histopathologic examination of the brain. In the infected mice
      treated for 2 wk with aminoguanidine, we observed an increase in the number of
      toxoplasma tachyzoites and intracellular cysts accompanied by an exacerbated
      inflammation of the brain tissue compared with that in controls. When spleen
      cells from infected mice were stimulated in culture with toxoplasma Ag, there was
      a marked cytotoxic effect on cells collected during the acute stage of infection
      and an inhibition of proliferation of the remaining viable lymphocytes. These
      effects were correlated with high levels of NO and PGE2 production. The
      suppression of NO synthesis prevented cell death and restored the lymphocyte
      proliferative response as well as lymphokine production. The neutralization of
      IFN-gamma or TNF-alpha had no effect on NO production in the cultures of infected
      mouse spleen cells. Cultures in which purified macrophages and lymphocytes from
      infected and naive mice were mixed indicated that the production of NO was
      dependent on lymphocyte activation. In the later stages of infection, when the
      production of NO was abating, preventing PGE2 secretion with indomethacin also
      increased the lymphocyte proliferative response. We conclude that the opposing
      effects of NO in toxoplasmosis, which protects against Toxoplasma gondii and at
      the same time limits the immune response, probably contribute to the
      establishment of the characteristic chronic state of host parasite equilibrium.

PMID- 8568249
TI  - The T cell receptor gene usage by simian immunodeficiency virus gag-specific
      cytotoxic T lymphocytes in rhesus monkeys.
AB  - MHC class I-restricted CTL play an important role in limiting the spread of HIV-1
      in the infected individual. Elucidating the molecular interactions of CTL with
      the virus is, therefore, of central importance for characterizing the immune
      control of this infection. In exploring this CTL response, we have defined the
      TCR usage by SIVmac Gag-specific CTL in rhesus monkeys. Thirty-nine CTL clones
      were generated from PBL of three SIVmac-infected monkeys expressing the MHC class
      I Mamu-A*01 gene product, all of which were shown to recognize a single SIVmac
      Gag peptide in association with Mamu-A*01. Sixty-six percent of CTL clones
      derived from two monkeys early after infection expressed TCR genes of the V beta
      13 family; 70% of these V beta 13+ CTL clones expressed a TCR heterodimer
      composed of V alpha 1 and V beta 13 gene products. In addition, there appeared to
      be a selection of a single conserved amino acid and restricted CDR3 lengths in
      junctional regions of TCR beta-chains expressed by the V beta 13+ CTL clones.
      These findings indicate significant structural constraints on the CTL-TCR
      interaction with the AIDS virus. Interestingly, 55% of the CTL clones derived
      from the third animal at a later time following infection employed genes of the V
      beta 6 family in their TCR. Despite the preferential use of TCR V family genes by
      the CTL clones, the SIVmac Gag-specific CTL response was clearly polyclonal; TCR
      expressed by these CTL clones displayed varied sequences in their CDR3 regions.
      Other V gene families, including V beta 23, V alpha 8, and V alpha 20, were used
      in TCR expressed by SIVmac Gag-specific CTL clones. These studies, therefore,
      indicate that the TCR repertoire of SIVmac Gag-specific CTL that share a peptide
      and MHC class I recognition specificity can be diverse. Such a broad CTL-TCR
      repertoire may be advantageous for the host in containing an AIDS virus
      infection.

PMID- 8568251
TI  - T cell-derived IL-3 induces the production of IL-4 by non-B, non-T cells to
      amplify the Th2-cytokine response to a non-parasite antigen in Schistosoma
      mansoni-infected mice.
AB  - We describe a novel amplification mechanism underlying the increased early IL-4
      production observed in Schistosoma mansoni-infected mice in response to a non
      parasite Ag, sperm whale myoglobin (SwMb). Earlier studies have shown that
      splenic Fc epsilon R+ non-B, non-T (NBNT) cells from schistosome-infected mice
      secrete IL-4 after stimulation with parasite Ag. We now demonstrate that purified
      NBNT cells from SwMb-immunized S. mansoni-infected mice do not respond directly
      to SwMb, but produce IL-4 in response to IL-3. Accordingly, we show that the
      early SwMb-specific IL-4 response of spleen cells (SC) from immunized infected
      mice is dependent on IL-3 and on CD4+ T cells. Thus, most of the early SwMb
      induced IL-4 from SC of infected mice appears to be produced by NBNT cells
      triggered by IL-3 synthesized by SwMb-specific CD4+ T cells. IL-3-induced IL-4
      production was also observed in purified NBNT cells from immunized uninfected
      mice, but the frequency and/or IL-4-producing capacity of splenic IL-3-responsive
      cells was found to be 8 to 16 times higher in immunized infected animals. IL-4
      production by purified CD4+ cells from immunized infected mice was also seen
      after SwMb stimulation, but this response showed slower kinetics than those of
      total SC, was IL-3-independent, and on average threefold greater than that by
      CD4+ cells from immunized uninfected controls. Thus, increased SwMb-induced IL-4
      production in immunized S. mansoni-infected mice results from direct synthesis by
      CD4+ T cells, as well as their stimulation via IL-3 of an expanded population of
      NBNT cells. The latter pathway may serve as an amplification loop for Th2
      cytokine responses.

PMID- 8568252
TI  - Mast cells process bacterial Ags through a phagocytic route for class I MHC
      presentation to T cells.
AB  - The pivotal role of mast cells in allergic reactions and inflammatory processes
      is well established and recent studies have suggested that mast cells may also
      have a role in specific immune responses. Because mast cells have been shown to
      phagocytose and kill enterobacteria, we wished to determine whether they could
      also process bacterial Ags for presentation to T cells. Using a model system in
      which a well-characterized T cell epitope is expressed within bacteria as a
      fusion protein, we demonstrate in this paper that mast cells are indeed capable
      of processing bacterial Ags for presentation through class I MHC molecules to T
      cell hybridomas after phagocytic uptake of live bacteria. Processing occurs from
      a number of Gram-negative enterobacteria including Salmonella typhimurium and
      Escherichia coli. Parallel assays show that processing of the model Ag from
      enterobacteria by mast cells is similar in efficiency to processing by peritoneal
      macrophages. Consistent with earlier observations demonstrating a function of the
      bacterial fimbrial protein FimH in promoting bacterial binding to mast cells, the
      magnitude of the Ag processing response of E. coli is influenced by bacterial
      expression of FimH. Taken together, these observations extend the range of cell
      types capable of the phagocytic pathway of Ag processing and suggest that mast
      cells may have a previously unrecognized role in the induction of specific immune
      responses to bacteria.

PMID- 8568253
TI  - CTL epitope generation is tightly linked to cellular proteolysis of a Listeria
      monocytogenes antigen.
AB  - Listeria monocytogenes is a pathogenic intracellular bacterium that secretes
      proteins into the cytosol of host cells. A major secreted protein, p60, is
      processed by the host cell into the nonamer peptides p60 217-225 and p60 449-457,
      which are presented to CTL by H-2Kd MHC class I molecules. Herein, we use two
      membrane permeable peptide aldehyde protease inhibitors, LLnL and Z-LLF, to
      inhibit cytosolic proteolysis in L. monocytogenes-infected cells. These
      inhibitors, which have been shown to inhibit proteasomes, completely abrogate
      cytosolic p60 degradation. The effect of LLnL and Z-LLF on p60 epitope generation
      was determined by acid-eluting, HPLC-purifying, and quantifying p60 217-225 and
      p60 449-457 from infected cells. We show a direct linkage between p60 degradation
      and epitope generation. However, the two inhibitors have quantitatively different
      effects on the generation of the two epitopes. Our findings implicate proteasomes
      in the earliest stages of Ag degradation and suggest that different CTL epitopes
      can be generated by distinct proteolytic processes.

PMID- 8568254
TI  - Regulation of mucosal and systemic antibody responses by T helper cell subsets,
      macrophages, and derived cytokines following oral immunization with live
      recombinant Salmonella.
AB  - We have assessed regulatory Th cell and cytokine responses in mice after oral
      immunization with recombinant Salmonella (BRD 847) expressing fragment C of
      tetanus toxoid, since little information is available to explain how these
      vectors induce mucosal IgA responses. A single dose of BRD 847 elicited serum
      IgG2a and mucosal IgA anti-tetanus toxoid Ab responses. To assess Th1-and Th2
      type responses, CD4+ T cells from Peyer's patches and spleen were restimulated in
      vitro, and cytokine-specific ELISPOT, ELISA, and reverse transcriptase-PCR assays
      were used to assess cytokine patterns. CD4+ T cells produced IFN-gamma and IL-2
      as well as IL-10, but not IL-4 or IL-5. Although IL-6 was elevated, further
      purification of cells from in vitro cultures into CD4+ Mac-1- T cells and Mac-1+
      CD4- cells revealed that only the latter cell population had consistently
      elevated IL-6 gene expression, whereas both sorted populations exhibited
      increased IFN-gamma and IL-10 gene expression. Thus, orally administered
      recombinant Salmonella expressing fragment C of tetanus toxoid elicited dominant
      Ag-specific Th1-type responses together with Th2-type cells producing IL-10 in
      both mucosal and systemic tissues. Macrophages producing IL-6 were also evident.
      Our results are consistent with the suggestion that Ag-specific Th1 cells and
      their derived cytokines, IFN-gamma and IL-2, and Th2-derived IL-10 together with
      IL-6 produced by macrophages provide important signals for the development of
      mucosal IgA and serum IgG subclass responses in the absence of preferential
      expression of Th2 cytokines IL-4 and IL-5.

PMID- 8568255
TI  - Roles of platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) in natural
      killer cell transendothelial migration and beta 2 integrin activation.
AB  - Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a glycoprotein
      expressed on the surfaces of monocytes, neutrophils, platelets, a subpopulation
      of T cells, and, as described in this work, on NK cells. It is also concentrated
      at the junctions between endothelial cells (EC) in culture, and is expressed on
      continuous endothelia in all tissues. PECAM has been shown to be involved in
      monocyte and neutrophil transendothelial migration in vitro and in vivo. The
      function of PECAM in NK cell interaction with EC has never been studied. In this
      work, we demonstrate that ligation of PECAM on the surface of NK cells activates
      their beta 2 integrins. Anti-PECAM Abs added to NK cells caused a 2.5- to 4-fold
      increase in the binding of these cells to monolayers of EC or 3T3 cells
      transfected with ICAM-1, and this was inhibited by a mAb against CD18. PECAM also
      plays a role in NK cell transendothelial migration. Anti-PECAM Abs inhibited 50%
      of NK cell transmigration through resting EC in an in vitro system. The
      transmigration of CD56dim and CD56bright cells was inhibited equally. IFN-gamma
      increased NK cell transmigration; the transmigration of CD56bright cells was
      increased to a much greater extent than CD56dim transmigration (4-fold vs 1.5
      fold). Anti-PECAM inhibited the transmigration of CD56dim cells by 30%, while
      that of CD56bright cells was not blocked. These studies demonstrate that PECAM-1
      could play an important role in the extravasation of NK cells into tissues for
      constitutive surveillance and into sites of inflammation.

PMID- 8568256
TI  - Age-associated differences in TNF-alpha and nitric oxide production in endotoxic
      mice.
AB  - Gram-negative bacterial infection is a common cause of septic shock in the older
      population in the U.S. We employed an experimental model of sepsis to study the
      cause of increased lethality due to LPS in older animals. Three ages of male
      B6JC3J/Nia mice, young (2 mo old), mature (12 mo old), and senescent (24 mo old),
      were treated with bacterial LPS, and the older mice were found to be 10 times
      more sensitive to LPS lethality. Increased sensitivity to LPS in senescent mice
      correlated with significantly elevated plasma TNF-alpha and nitric oxide levels.
      Abs to TNF-alpha afforded aged animals passive protection against a supralethal
      dose of LPS, establishing a central role for TNF in the increased sensitivity to
      LPS seen in the aged animals. Other cytokines, such as IL-1 and IFN-gamma,
      appeared secondary to TNF and nitric oxide in the age-associated sensitivity to
      LPS. Plasma corticosterone levels were increased by LPS at a time when maximal
      levels of plasma TNF-alpha were observed in both age groups, although the
      kinetics of hormone production and the magnitude of TNF-alpha release varied
      among the age groups. Exogenously administered dexamethasone protected senescent
      animals given a high dose of LPS, by decreasing cytokine levels. The increased
      sensitivity to LPS observed in aged animals, therefore, seems to be due to
      excessive TNF and nitric oxide production, resulting from perturbed endogenous
      hormonal control of cytokine production.

PMID- 8568257
TI  - Mouse microglial cells express a plasma membrane pore gated by extracellular ATP.
AB  - We have investigated responses to extracellular ATP (ATPe) in the microglial cell
      lines N9 and N13 and in freshly isolated mouse microglial cells. Upon stimulation
      with this nucleotide, N9 and N13 cells underwent an increase in the cytoplasmic
      free Ca2+ concentration ([Ca2+]i), a sustained depolarization of the plasma
      membrane, and an uptake of extracellular markers such as ethidium bromide and
      lucifer yellow; increases in plasma membrane permeability were paralleled by
      striking morphologic changes. ATPe, as well as other nucleotides, activated a
      spiking Ca2+ release from intracellular stores; however, only ATPe was also able
      to cause a massive transmembrane Ca2+ influx. The ATP analogue 2'- and 3'-O-(4
      benzoylbenzoyl)-ATP (BzATP) triggered a sustained Ca2+ influx accompanied by
      little release from stores. The ATP derivative oxidized ATP (oATP) strongly
      inhibited Ca2+ influx, minimally affecting Ca2+ release. From ATPe-sensitive
      microglial cell lines, we selected several ATPe-resistant clones that showed
      complete lack of ATPe-mediated plasma membrane permeability changes, although
      they retained the Ca2+ mobilization response from intracellular stores. ATPe
      dependent plasma membrane permeability changes were also greatly reduced in
      growth-arrested microglial cells. Finally, ATPe triggered IL-1 beta release from
      wild-type but not ATPe-resistant microglial cells. These results show that
      microglial cells express at least two purinergic receptor subtypes, metabotropic
      (P2Y) and ionotropic (P2Z), and that the latter is modulated during cell cycle
      and coupled to IL-1 beta release.

PMID- 8568258
TI  - Reactive oxygen intermediates as regulators of TNF-alpha production in rat lung
      inflammation induced by silica.
AB  - Exposure to mineral dusts such as silica has been associated with progressive
      pulmonary inflammation and fibrosis. There is evidence that the release of
      reactive oxygen intermediates (ROI) and cytokines by alveolar macrophages (AM) is
      involved in lung injury associated with silica exposure. However, the chronology
      and relationship between these two mediators are poorly understood. In this
      study, an animal model of silicosis has been used, allowing simultaneous follow
      up of lung histopathologic state, AM TNF-alpha production at the protein
      (biologic assay) and mRNA (reverse transcriptase-PCR) levels, and the release of
      ROI (luminol-dependent chemiluminescence), after bronchoalveolar lavages. In
      particular, it has been shown that intratracheal instillation of silica (50
      mg/kg) in rats led to fibrosis characterized by cellular interstitial infiltrates
      with granulomas, and in AM, it led to 1) an early and continuous increase in 12-O
      tetradecanoylphorbol-13-acetate- or zymosan-triggered ROI production (days 1, 3,
      14, and 28 post-treatment), and 2) a rise of TNF-alpha mRNA expression and
      protein secretion on days 3 and 14. A free radical scavenger pretreatment (N-ter
      butyl-alpha-phenylnitrone) reversed lung histopathologic changes and decreased AM
      ROI production and TNF-alpha expression at the level of mRNA. These findings
      suggest that ROI production is an important primary event determining the silica
      induced inflammatory process. ROI may act in an autocrine or paracrine manner and
      regulate TNF-alpha production by a mechanism promoting gene expression. The
      critical role of this cytokine in the pathogenesis of silicosis was confirmed by
      anti-TNF-alpha Ab treatment.

PMID- 8568259
TI  - Dermal microvascular endothelial cells express CD32 receptors in vivo and in
      vitro.
AB  - Immune complexes are thought to be the major cause of cutaneous necrotizing
      vasculitis, but the mechanism of immune complex targeting to specific vessels is
      largely unknown. In myelomonocytic cells, immune complex binding and receptor
      mediated endocytosis are mediated by Fc gamma R. We asked whether dermal
      microvascular endothelial cells (DMEC) express Fc gamma Rs. In cryostat sections
      of normal human skin, mAb IV.3 or AT10, both recognizing CD32 (Fc gamma RII),
      localizes to the luminal surface of DMEC of the superficial but not of the deep
      vascular plexus. All DMEC do not express CD16 (Fc gamma RIII) or CD64 (Fc gamma
      RI) molecules. Adult skin-derived DMEC in culture express CD32 (Fc gamma RII)
      molecules, as measured by FACS, but are negative for CD16 or CD64. HUVEC, tested
      for comparison, do not express CD16, 32, or 64 proteins. By reverse-transcriptase
      PCR and subsequent Southern blot analysis, the isoform of the CD32 molecule
      expressed on DMEC is determined as Fc gamma RIIa. HUVEC do not contain Fc gamma
      RIIa or Fc gamma RIIb mRNA. In DMEC, Fc gamma RIIa cross-linking results in
      immediate intracellular free Ca2+ ([Ca2+]i) concentration fluxes and in rapid
      internalization of the occupied receptors. We conclude that DMEC are equipped
      with fully functional Fc gamma RIIa molecules.

PMID- 8568260
TI  - In vitro culture of human peripheral blood monocytes induces hyaluronan binding
      and up-regulates monocyte variant CD44 isoform expression.
AB  - CD44 is a cell surface proteoglycan homologous to cartilage link protein that
      serves as a receptor for hyaluronan (HA). CD44 isoforms include an unspliced 80-
      to 90-kDa standard form (CD44S) and isoforms derived from alternative splicing of
      nine CD44 variant exons (CD44V). Ligation of CD44 isoforms on monocytes induces
      the production of IL-1 and TNF-alpha. In addition, CD44 mAbs and HA inhibit HIV
      infection of monocytes by monocytotropic HIV, but do not inhibit T cell tropic
      HIV infectivity of T cells. To determine the ability of PB lymphocytes and
      monocytes to bind HA and to define and compare CD44 isoforms present on PB
      monocytes and lymphocytes, we studied PBMC using a panel of CD44 mAbs, HA-FITC,
      flow cytometry, and Western blot analysis. We found that freshly isolated PB
      monocytes and lymphocytes did not bind soluble HA. However, in vitro culture of
      PBMC for 8 to 16 h resulted in CD44-dependent HA-FITC binding to monocytes, but
      not to lymphocytes. Western blot and flow cytometry analyses using CD44 mAbs
      demonstrated selective expression of high m.w. CD44V isoforms on cultured
      monocytes, but not on lymphocytes. Finally, tissue macrophages and multinucleated
      giant cells from patients with inflammatory lesions expressed CD44V6- and CD44V9
      containing CD44 isoforms in vivo, suggesting that CD44V expression is associated
      with differentiation of monocytes to tissue macrophages in vivo in inflammatory
      sites. Taken together, our data demonstrate that PB monocytes, but not T or B
      lymphocytes, acquire the ability to bind HA and up-regulate CD44V expression
      after in vitro culture.

PMID- 8568261
TI  - Specificity and reciprocity in the interactions between TGF-beta and macrophage
      inflammatory protein-1 alpha.
AB  - TGF-beta and macrophage inflammatory protein-1 alpha (MIP-1 alpha) appear to
      share a number of biologic properties. We have been attempting to examine the
      interactions between these two peptides in the hope of gaining an insight into
      the basis for the apparent functional redundancy. Our earlier observations have
      indicated that TGF-beta is a potent down-regulator of MIP-1 alpha and MIP-1 beta
      expression in bone marrow macrophages and also of MIP-1 alpha receptor numbers on
      FDCPmix cells. We now demonstrate that the interplay between TGF-beta and MIP-1
      alpha beta is relatively specific, in that only MIP-1 alpha and MIP-1 beta appear
      to be potently suppressed by TGF-beta, and that this suppressive activity is
      restricted to the direct TGF-beta isoforms. Activin and the bone morphogenetic
      proteins (BMPs) appear to be inactive in this regard. We also demonstrate the
      existence of an endogenous TGF-beta-mediated block that acts to minimize MIP-1
      alpha expression in TGF-beta-expressing macrophages. This coupled with the
      observations that MIP-1 alpha can induce expression of TGF-beta suggests to us
      that the complex interactions between MIP-1 alpha and MIP-1 beta and the direct
      TGF-beta isoforms (beta 1, beta 2, and beta 3) act to ensure minimized MIP-1
      alpha beta expression and maximized TGF-beta expression. However, such interplay
      may also be dependent on the local cytokine or inflammatory profile to which the
      cells are exposed.

PMID- 8568262
TI  - The animal lectin galectin-3 interacts with bacterial lipopolysaccharides via two
      independent sites.
AB  - Galectin-3 is a beta-galactoside binding protein expressed by activated
      macrophages, epithelial cells, and certain other cell types. Galectin-3 has a C
      terminal carbohydrate binding domain, an N-terminal part consisting of a proline-
      and glycine-rich repetitive domain, and a small N-terminal domain. Two
      independent LPS binding sites on galectin-3 were demonstrated by binding of
      biotinylated LPS to immobilized recombinant galectin-3. One appears to be the
      carbohydrate binding site in the C-terminal domain that confers binding of LPS
      from Klebsiella pneumoniae that has a beta-galactoside-containing polysaccharide
      chain. This binding is best demonstrated using galectin-3 immunocaptured by a mAb
      to the N-terminal part (M3/38) and is inhibited by lactose. In contrast,
      Salmonella minnesota R7 LPS (Rd mutant), which is devoid of beta-galactosides,
      appears to bind to a site within the N-terminal part of galectin-3. This
      interaction is best demonstrated using galectin-3 directly immobilized in wells,
      and it is inhibited by the Ab M3/38, but not by lactose. Binding inhibition by
      polymyxin B and the profile of inhibition by a panel of LPSs with different
      amounts of the inner and outer cores present indicate that this second binding
      site recognizes the lipid A/inner core region of LPSs.

PMID- 8568263
TI  - Effect of overexpression of human Cu,Zn superoxide dismutase in transgenic mice
      on macrophage functions.
AB  - Properties of macrophages from transgenic mice with the human Cu,Zn superoxide
      dismutase (SOD) gene under the control of the mouse hydroxyl-methyl coenzyme A
      reductase (HMGCR) promoter were studied. In these mice, a twofold overproduction
      of Cu,Zn SOD in intraperitoneal macrophages resulted in the significant reduction
      of their microbicidal and fungicidal activity. Intracellular production and
      release of H2O2 in macrophages from transgenic mice activated by PMA was found to
      be significantly increased, whereas extracellular release of O2- was inhibited.
      When treated with LPS or LPS plus IFN-gamma, macrophages from transgenic mice
      were found to produce less nitric oxide (NO) than normal mice, suggesting that
      the nitrocompound metabolism in macrophages overproducing Cu,Zn SOD was also
      affected. Analysis of NF-kappa B DNA-binding activity and antiphosphotyrosine
      immunoblotting experiments suggest that impairment of macrophage functions may be
      attributed to the inhibition of signal transduction pathways as well as to
      changes in oxygen radical metabolism. The present data support the notion that
      antioxidant enzymes play important roles in the function of macrophages.

PMID- 8568264
TI  - Crucial role of 55-kilodalton TNF receptor in TNF-induced adhesion molecule
      expression and leukocyte organ infiltration.
AB  - Stimulation of leukocyte adhesion to the endothelium by TNF is mediated by the up
      regulation of adhesion molecules on the endothelial cell surface. C57BL/6 mice
      and syngenic 55-kDa TNF receptor-deficient mice (TNFRp55-/- mice) were challenged
      with TNF, and the kinetics of intracellular adhesion molecule-1, ICAM-1, mucosal
      addressin cell adhesion molecule-1, vascular adhesion molecule-1 (VCAM-1), and E
      selectin expression were examined in various organs. TNF induced sustained VCAM-1
      expression within 4 h in lung, liver, and kidney. In the lungs, but not in other
      organs, transient E-selectin expression was induced by TNF within 0.5 h and
      peaked at 4 h. The TNF-induced expression of VCAM-1 and E-selectin was found to
      be exclusively controlled by the 55-kDa TNF-receptor (TNFRp55) as demonstrated by
      analysis of TNFRp55-/- mice. Furthermore, TNF triggered mononuclear cell and
      neutrophil infiltration of lung, liver, and kidney in C57BL/6 mice but not
      TNFRp55-/- mice. Interestingly, MAdCAM-1 expression in the marginal sinus of the
      spleen was detected in wild-type mice but was absent in TNFRp55-/- mice.
      Together, the data suggest that in vivo the 55-kDa TNF receptor mediates the
      induction of VCAM-1 and E-selectin expression and is critically involved in the
      control of leukocyte organ infiltration.

PMID- 8568265
TI  - Acute phase levels of C-reactive protein enhance IL-1 beta and IL-1ra production
      by human blood monocytes but inhibit IL-1 beta and IL-1ra production by alveolar
      macrophages.
AB  - C-reactive protein (CRP), the major acute phase protein in humans, was purified
      free of endotoxin (LPS) (< 10 pg of LPS/mg of purified CRP) and evaluated for its
      ability to modulate LPS-induced production of IL-1 beta and IL-1 receptor
      antagonist (IL-1ra) from human PBMC and lung macrophages. PBMC (5 x 10(6)/ml)
      released low levels of IL-1 beta in response to either CRP (250 micrograms/ml) or
      LPS (100 ng/ml) for 18 h (0.3 +/- 0.1 and 1.5 +/- 0.7 ng/ml, respectively).
      However, when CRP (250 micrograms/ml) and LPS (100 ng/ml) were combined, PBMC
      released 9.7 +/- 2.9 ng/ml (p < 0.001 vs LPS alone). This synergy was removed by
      immunodepletion of CRP before stimulation. With respect to IL-1ra, although CRP
      induced IL-1ra production from PBMC (0.8 +/- 0.3 ng/ml control, 2.6 +/- 1.3 ng/ml
      with CRP), CRP did not synergize with LPS for IL-1ra production (15.0 +/- 0.7
      ng/ml LPS alone vs 15.4 +/- 1.4 ng/ml LPS and CRP). In contrast, lung macrophages
      responded to CRP quite differently than PBMC. Macrophages (10(6)/ml) were not
      stimulated to produce IL-1 beta or IL-1ra by CRP alone. When combined with LPS,
      CRP inhibited IL-1 beta and IL-1ra release induced by LPS (for IL-1 beta release,
      LPS induced 3.0 +/- 1.7 ng/ml vs 1.1 +/- 0.4 for combined LPS and CRP; for IL-1ra
      release, LPS induced 12.9 +/- 2.3 ng/ml vs 7.6 +/- 2.3 ng/ml for combined LPS and
      CRP). These data suggest that acute phase levels of CRP may have divergent
      effects depending on the target population. CRP may be largely proinflammatory to
      blood monocytes responding to LPS since IL-1 beta production is augmented over IL
      1ra production. However, in tissue compartments the effects of CRP may be largely
      immunosuppressive to LPS-induced tissue macrophage IL-1 beta production.

PMID- 8568266
TI  - Ligand-independent activation of the glucocorticoid receptor by ursodeoxycholic
      acid. Repression of IFN-gamma-induced MHC class II gene expression via a
      glucocorticoid receptor-dependent pathway.
AB  - The therapeutic effectiveness of ursodeoxycholic acid (UDCA) for various
      autoimmune liver diseases strongly indicates that UDCA possesses immunomodulatory
      activities. Experimental evidence also supports this notion, since, for example,
      UDCA has been shown to suppress secretion of IL-2, IL-4, and IFN-gamma from
      activated T lymphocytes, and Ig production from B lymphocytes. To investigate the
      mechanical background of UDCA-mediated immunomodulation, we asked whether UDCA
      interacts with the intracellular signal transduction pathway, especially whether
      it is involved in immunosuppressive glucocorticoid hormone action. For this
      purpose, we used a cloned Chinese hamster ovary cell line, CHOpMTGR, in which
      glucocorticoid receptor cDNA was stably integrated. In immunocytochemical
      analysis, we found that treatment with UDCA promoted the nuclear translocation of
      the glucocorticoid receptor in a ligand-independent fashion, which was further
      confirmed by immunoprecipitation assays. Moreover, the translocated
      glucocorticoid receptor demonstrated sequence-specific DNA binding activity.
      Transient transfection experiments revealed that treatment of the cells with UDCA
      marginally enhanced glucocorticoid-responsive gene expression. We also showed
      that UDCA suppressed IFN-gamma-mediated induction of MHC class II gene expression
      via the glucocorticoid receptor-mediated pathway. Together, UDCA-dependent
      promotion of translocation of the glucocorticoid receptor may be associated with,
      at least in part, its immunomodulatory action through glucocorticoid receptor
      mediated gene regulation.

PMID- 8568267
TI  - TNF/IL-1-inducible protein TSG-6 potentiates plasmin inhibition by inter-alpha
      inhibitor and exerts a strong anti-inflammatory effect in vivo.
AB  - TNF-stimulated gene 6 (tsg6), encoding a 35-kDa secretory glycoprotein (TSG-6),
      is induced in fibroblasts, chondrocytes, synovial cells, and mononuclear cells by
      the proinflammatory cytokines TNF-alpha and IL-1, or by LPS. Large amounts of TSG
      6 protein were found in synovial fluids of patients with rheumatoid arthritis.
      TSG-6 protein forms a stable complex with components of the serine protease
      inhibitor, inter-alpha-inhibitor (I alpha I). In this work, we show that TSG-6
      potentiates the inhibitory effect of l alpha l on the protease activity of
      plasmin. The plasmin/plasminogen activator system is important in the protease
      network associated with inflammation. To test the hypothesis that through their
      cooperative inhibitory effect on plasmin TSG-6 and l alpha l can modulate the
      protease network and thus inhibit inflammation, we examined the effect of TSG-6
      on experimentally induced inflammation. Human recombinant TSG-6 protein showed a
      potent anti-inflammatory activity in the murine air pouch model of carrageenan-
      or IL-1-induced acute inflammation. The inhibitory effect of locally administered
      TSG-6 on the IL-1-induced cellular infiltration was comparable with that of
      systemic dexamethasone treatment. Two mutant TSG-6 proteins with single amino
      acid substitutions close to the N terminus showed a complete or partial loss of
      anti-inflammatory activity. The anti-inflammatory effect of the TNF/IL-1
      inducible TSG-6 protein, along with its ability to inhibit protease action
      through interaction with l alpha l, suggests that TSG-6 production during
      inflammation is part of a negative feedback loop operating through the protease
      network.

PMID- 8568268
TI  - The main IgE-binding epitope of a major latex allergen, prohevein, is present in
      its N-terminal 43-amino acid fragment, hevein.
AB  - Polypeptides of natural rubber latex (NRL) that elute from surgeon's gloves and
      other manufactured rubber products can sensitize exposed individuals and elicit
      severe hypersensitivity reactions. Previously, we showed that prohevein is a
      major allergen in NRL, the source material for rubber manufacturing. To analyze
      which region of the molecule carries the main IgE-binding epitope(s), we purified
      prohevein and its C-domain from NRL by gel filtration, reverse phase
      chromatography, and electroelution. In immunoblotting, prohevein bound IgE from
      15 of 20 (75%), and the prohevein C-domain from 3 of 20 (15%) latex-allergic
      patient sera. In ELISA, 36 of 52 (69%) patient sera showed IgE binding to
      prohevein, whereas 11 of 52 (21%) sera had IgE to prohevein C-domain. We then
      purified from a brand of highly allergenic surgeon's gloves six hydrophilic
      peptides that revealed in amino-terminal sequencing 100% identity to the N
      terminus of prohevein. In mass spectrometry, all purified peptides gave a
      molecular mass of 4719 +/- 1.9 daltons, which corresponds to the molecular mass
      of hevein (4719.1 daltons), a 43-amino acid N-terminal fragment of prohevein.
      Purified hevein inhibited 72% of IgE binding from pooled sera of NRL-allergic
      patients to solid phase glove extract and 45% of IgE binding to solid phase NRL.
      Of the 43 NRL-allergic patient sera tested, 56% showed IgE Abs to purified hevein
      in ELISA. In skin prick testing, purified hevein elicited positive reactions in
      three-quarters of the latex-allergic patients tested. These results indicate that
      the majority of prohevein's IgE-binding ability resides in its N-terminal
      fragment, known as hevein. In one highly allergenic latex glove examined, the
      majority of IgE-binding ability was attributable to hevein molecules, suggesting
      that these peptides can be significant sensitizers in NRL allergy.

PMID- 8568269
TI  - IL-12 expression in AIDS-related lymphoma B cell lines.
AB  - IL-12 is a 70-kDa heterodimer formed by the 40-kDa heavy chain (p40) and the 35
      kDa light chain (p35). Twenty-five Burkitt's lymphoma cell lines (CL) and seven
      normal lymphoblastoid B CL were studied. The Burkitt's CL included AIDS
      associated B CL (AABCL) (7 EBV+/2 EBV-) and non-AABCL (8 EBV+/8 EBV-). Reverse
      transcription-PCR detected p40 in EBV+ AABCL (7 of 7), EBV+ non-AABCL (3 of 8),
      and normal lymphoblastoid B CL (6 of 6) but not in EBV- CL (0 of 10). p35 mRNA
      was detected in 30 of 30 CL. Constitutive secretion of p40 was found in 7 of 7
      EBV+ AABCL (range, 341-18,086 pg/ml) and p70 in 3 of 7 EBV+ AABCL (range, 25-197
      pg/ml), but in only 1 of 8 EBV+ non-AABCL and 0 of 7 normal lymphoblastoid CL.
      PMA stimulated p40 secretion in 7 of 7 EBV+ AABCL and p70 secretion in 5 of 7
      EBV+ AABCL. PMA also triggered p40 and p70 secretion in 2 EBV+ non-AABCL and in 3
      of 7 normal lymphoblastoid CL. No IL-12 secretion was detected in 10 EBV- CL,
      including EBV- AABCL. The CL produced IL-10, a known inhibitor of IL-12, but anti
      IL-10 Abs did not neutralize IL-12. Similarly, neutralizing anti-IFN gamma Abs or
      IFN gamma did not affect B cell IL-12. For IL-12R studies, reverse transcription
      PCR and 125I-IL-12 binding assays were performed. Although all CL tested showed
      mRNA accumulation for one of the IL-12R components, IL-12 binding sites were
      detected in only 1 of 30 CL. Our data suggest that: 1) AABCL constitutively
      secrete large amounts of IL-12, contrasting with low IL-12 production by HIV-1
      infected PBMC; 2) lack of IL-12 expression in EBV- AABCL suggests that in vivo
      exposure of B cells to HIV-1 only does not induce IL-12 secretion and that both
      HIV-1 and EBV are required; 3) the autocrine-negative effect of IL-10 on IL-12 in
      monocytes and the enhancing effect of IFN gamma on IL-12 secretion do not apply
      to B cells derived from AIDS patients.

PMID- 8568270
TI  - HIV-1-Tat modulates the function of monocytes and alters their interactions with
      microvessel endothelial cells. A mechanism of HIV pathogenesis.
AB  - Monocytes are major targets of HIV infection in patients with AIDS. In vitro
      infection of monocytes with HIV is associated with increased expression of beta 2
      integrins, which increases both monocyte aggregation and monocyte/endothelial
      adhesion as well as monocyte metalloproteinase (MMP-9) expression. Treatment of
      primary monocytes with soluble HIV-Tat protein mimicked many of the properties of
      HIV infection of monocytes. Tat treatment up-regulated the expression of the beta
      2 integrins, which was associated with the formation of large aggregates of
      monocytes and increased adhesion to endothelial monolayers. Treatment of
      monocytes with Tat increased their adhesion to both untreated and TNF-alpha
      treated endothelial monolayers, and adhesion was inhibited by inclusion of anti
      beta 2 and anti-ICAM-1 Abs. The increased adhesion of activated monocytes was
      accompanied by substantial disruption of the endothelial monolayers, with
      retraction or detachment of individual endothelial cells. Tat treatment of
      monocytes up-regulated the synthesis and release of the protease MMP-9, providing
      a potential mechanism to explain endothelial cell/basement membrane detachment.
      Thus, extracellular Tat is capable of activating monocytes even in the absence of
      HIV infection. Our studies demonstrate that many of the effects of HIV infection
      on monocyte homotypic and heterotypic adhesion, protease secretion, and
      disruption of the endothelium can be mimicked by treatment with HIV-Tat protein
      alone. These results suggest a mechanism where monocytes could be inappropriately
      activated by HIV-Tat, secreted by HIV-infected cells, causing them to extravasate
      into underlying tissues and ultimately contribute to tissue damage as seen during
      the progression of AIDS.

PMID- 8568271
TI  - In vivo blockade of TNF-alpha by intravenous infusion of a chimeric monoclonal
      TNF-alpha antibody in patients with rheumatoid arthritis. Short term cellular and
      molecular effects.
AB  - Due to the unknown etiology of RA, specific treatment is not available. Recently,
      in a double-blinded, placebo-controlled clinical trial, in vivo blockade of TNF
      alpha by a single infusion of a chimeric TNF-alpha-blocking mAb, cA2, has proven
      to be highly effective in the treatment of RA. In parallel to this trial, we
      tested the consequences of cA2 infusion in ex vivo and in vitro experiments. In
      this paper, we describe an increase in CD4+ and CD8+ T lymphocyte counts on day 1
      and a marked decrease in monocyte counts preferentially on day 7 after cA2
      treatment, without major changes in B lymphocyte or NK cell counts. In addition,
      we found an increased responsiveness of PBMC to CD28 mAb/PMA, but not to CD3 mAb,
      superantigen staphylococcus enterotoxin B, or PHA on day 1 after infusion. The
      increase in DNA synthesis of PBMC was paralleled by increased IL-2 mRNA and IL-4
      mRNA expression and IL-2 protein secretion in culture supernatants after in vitro
      stimulation of PBMC with CD28 mAb/PMA. In PBMC, we did not find any significant
      changes in mRNA or protein expression of CD28 Ag or CD28 ligands, B7-1 and B7-2.
      Serum concentrations of IL-1 beta, IL-6, and soluble CD14 were significantly
      diminished after in vivo TNF-alpha blockade. We did not see relevant changes in
      granulocyte function in vitro after cA2 infusion. Finally, we observed a
      statistically significant decrease in slCAM-1 molecules in the serum of patients
      treated with verum compared with that in the serum of subjects given placebo.
      This change in slCAM-1 concentration was evident on days 1 and 7 after the
      infusion of 10 mg/kg cA2, whereas it occurred only on day 7 in the serum of
      patients treated with the low dose (1 mg/kg) of cA2.

PMID- 8568272
TI  - Establishment and characterization of a murine CD4+ T cell line and clone that
      induce experimental autoimmune uveoretinitis in B10.A mice.
AB  - B10.A mice develop experimental autoimmune uveoretinitis after active
      immunization with the interphotoreceptor retinoid-binding protein (IRBP). CD4+ T
      cells play an important role in the development of the disease. In this study we
      have isolated and characterized a CD4+ T cell line and a T cell clone that induce
      experimental autoimmune uveoretinitis when transferred into naive B10.A mice. The
      cell line was isolated from draining lymph nodes of IRBP-immunized animals by
      repeated cycles of IRBP stimulation. The line was shown to be pathogenic after 4
      rounds of in vitro stimulation with IRBP at 5 x 10(6) cells/mouse. A T cell clone
      derived from this line by limiting dilution was shown to be pathogenic when the
      same number of cells was injected; incidence and severity of disease, however,
      were much lower. After 16 rounds of IRBP-specific stimulation the cell line was
      pathogenic at 10(5) cells/mouse. Analysis of the V beta repertoire revealed that
      at this point the line was mostly composed of V beta 8.2- and V beta 6-positive
      cells (> 80% of the population). The uveitogenic clone expressed V beta 8.2. Both
      the T cell line and the clone elaborated an unrestricted lymphokine profile in
      vitro. However, when these cells were adoptively transferred into naive
      recipients, mRNA isolated from the uveitic retina showed only Th1 type cytokines.
      These data help to characterize the nature of pathogenic cells involved in ocular
      autoimmunity.

PMID- 8568273
TI  - Rat MHC-linked peptide transporter alleles strongly influence peptide binding by
      HLA-B27 but not B27-associated inflammatory disease.
AB  - Rats transgenic for the human MHC molecule HLA-B27 were used to study the effect
      of two alleles, cima and cimb, which are associated with peptide transport by the
      MHC-encoded Tap2 transporter, on the function of HLA-B27 as a restriction element
      for CTL recognition of the male H-Y minor H Ag and on the multisystem
      inflammatory disease characteristic of B27 transgenic rats. Anti-H-Y CTL
      generated in cima B27 transgenic rats lysed male B27 cimb/b targets significantly
      less well than cima/a or cima/b targets. Addition of exogenous H-Y peptides to
      male B27 cimb/b targets increased susceptibility to lysis to the level of cima/a
      targets. Male B27 cimb/b cells were less efficient than cima/a cells in
      competitively inhibiting CTL lysis of female B27 cima/a targets sensitized with
      exogenous H-Y peptides. 3H-Labeled peptides eluted from B27 molecules of
      lymphoblasts from rats of two cimb and three cima RT1 haplotypes showed that the
      cimb peptide pool favors comparatively longer and/or more hydrophobic peptides.
      These results indicate that RT1-linked Tap2 polymorphism in the rat strongly
      influences peptide loading of HLA-B27. Nonetheless, the prevalence and severity
      of multisystem inflammatory lesions were comparable in backcross rats bearing
      either cima/b or cimb/b. It thus appears either that binding of specific peptides
      to B27 is unimportant in the pathogenesis of B27-associated disease or that the
      critical peptides, unlike H-Y and many others, are not influenced by Tap
      transporter polymorphism.

PMID- 8568274
TI  - Lupus autoantibodies to double-stranded DNA cross-react with ribosomal protein
      S1.
AB  - One cDNA clone (G7) was isolated from a lambda gt11 human liver cDNA library by
      the reaction with a serum containing anti-dsDNA Abs and was ligated into pGEX-1
      lambda T vector. All the 10 SLE sera with anti-dsDNA, 2 samples of human
      monoclonal anti-dsDNA (33.C9 and 33.H11), and 2 affinity-purified anti-dsDNA Abs
      recognized the glutathione S-transferase fusion protein expressed by G7 (G7-FP).
      Ab binding to the recombinant protein expressed by G7 (G7-RP) and to G7-FP was
      inhibited completely by calf thymus dsDNA. The cDNA was 1314 nucleotides in
      length and contained an open reading frame encoding 352 amino acids. However, it
      seems to be a partial length cDNA because the affinity-purified Ab from G7-FP
      recognized only a 104-kDa protein on Western blot using MOLT4 cell extract. The
      nucleotide sequence of G7 was homologous (99% identity) to a cDNA encoding human
      ribosomal protein (r-protein) S1 homologue mRNA. The encoded protein contains
      repeating residues as a feature of r-proteins S1. Cytoplasmic and nucleolar
      staining of 33.H11 on indirect immunofluorescence (IF) using HEP 2 cells was
      inhibited by both G7-RP and calf thymus dsDNA. On ELISA, 33.H11 had a higher
      affinity for G7-RP than for DNA while 33.C9 had a higher affinity for DNA than
      for G7-RP and binds nuclei on IF. We conclude that G7 encodes a portion of human
      r-protein S1 and anti-dsDNA Abs cross-react with this protein.

PMID- 8568275
TI  - Evidence for distinct contributions of heavy and light chains to restriction of
      antibody recognition of the HIV-1 principal neutralization determinant.
AB  - We have used phage Ab display technology to analyze two mAbs to HIV-1 envelope
      proteins gp120 and gp41. From the data obtained we are able to demonstrate that
      the recognition of the principal neutralization determinant of different strains
      of HIV-1 by neutralizing mAb M77 is restricted by its heavy and light chains in
      different ways. Native M77 is able to recognize and neutralize HIV-1 strain IIIB
      through binding to the gp120 V3 loop. M77 is unable to recognize strains of HIV-1
      that differ on either the left or right side of the V3 loop tip. A chain-switched
      Fab fragment containing the M77 Fd fragment and a different light chain was able
      to recognize HIV-1 strains that differ from IIIB on the left side but not the
      right side of the V3 loop tip.

PMID- 8568276
TI  - IgM rheumatoid factors react with human class I HLA molecules.
AB  - Half of 30 human polyclonal IgM rheumatoid factors (RF) showed positive ELISA
      reactions with affinity-isolated human class I molecules (A2 and B7). Positive RF
      reactivity with isolated class I heavy chains indicated that anti-class I RF
      interaction did not merely reflect RF anti-beta 2m specificity. Cross-reactions
      between antigenic determinants on human IgG, class I molecules, and beta 2m
      reacting with RF could be demonstrated by ELISA inhibition. When gene products of
      A2 alpha 2 exons 2, 3, and 4 were synthesized as overlapping heptamers on
      polypropylene pins, six RF-reactive epitopes within solvent accessible class I
      HLA regions were identified: EPRAPWI, QEGPEYW, QTHRVDL (second A2 exon), EQLRAYL,
      GTCVEWL, and WLRRYLE (third A2 exon). Glycine-alanine substitution for each
      residue within these RF-reactive sites identified R48, W51, E55, Y107, R108,
      W147, Q155, and E172 as immunodominant residues for RF reactivity. Many of these
      RF-reactive class I regions also showed positive ELISA reactions with monoclonal
      human IgM RFs derived from rheumatoid arthritis synovial B cells. Whole serum
      from patients with rheumatoid arthritis showed a spectrum of IgM, IgA, and IgG
      Abs that adsorbed to and could be eluted from monomeric IgG or HLA A2 affinity
      columns. Normal serum similarly analyzed showed only trace reactions with IgG,
      A2, or beta 2m. Flow cytometry using RF incubated with A2 cell lines showed
      definite immunofluorescence reactivity with cell membranes not observed with
      normal non-RF IgM. Reactivity of human IgM RF with determinants on class I
      molecules may reflect antigenic overlap within several members of Ig gene
      superfamily products.

PMID- 8568277
TI  - Definition of a Trichophyton protein associated with delayed hypersensitivity in
      humans. Evidence for immediate (IgE and IgG4) and delayed hypersensitivity to a
      single protein.
AB  - Dermatophytes of the genus Trichophyton cause infections of human skin, nails,
      and hair. Unlike most Ags, Trichophyton can elicit either immediate (IH) or
      delayed (DH) hypersensitivity skin reactions. Previous studies isolated a 30-kDa
      Ag (Tri t 1) that caused IH skin tests. The study presented here used skin
      testing and in vitro T cell proliferation assays to monitor purification of an
      Ag, designated Protein IV, associated with DH reactions. Protein IV was purified
      by cation exchange HPLC; amino acid sequence analysis of the N-terminus and nine
      internal peptides (143 residues) revealed no homologies to Tri t 1 or to any
      other known proteins. A mAb-based ELISA was developed to measure Protein IV.
      Protein IV elicited DH skin reactions in subjects with a history of athlete's
      foot but also caused IH skin reactions. Serologic responses to Protein IV were
      studied in 59 adults who had been skin tested with Trichophyton extract. IH skin
      reactions were associated with a positive RAST (14/23) as well as with specific
      IgE (13/23) and IgG4 (14/23) Abs to Protein IV. DH skin tests were not associated
      with IgE or IgG4 Abs. IgE anti-Protein IV Abs were quantitatively correlated with
      IgG4 Abs (r = 0.57, p < 0.001). Specific IgG Abs to Protein IV were highest in IH
      subjects (gm = 230 U/ml), and lowest in those with DH (gm = 91 U/ml) or negative
      (gm = 81 U/ml) skin tests; furthermore, the prevalence of IgG Abs increased
      significantly with age. Protein IV is the first defined protein associated with
      both DH and IH skin reactions; these reactions are characterized by distinct
      serologic responses. The results establish that diverse immune responses in
      humans can be directed against the same protein.

PMID- 8568278
TI  - Production of polyhedra of the Autographa californica nuclear polyhedrosis virus
      using the Sf21 and Tn5B1-4 cell lines and comparison with host-derived polyhedra
      by bioassay.
AB  - Both wild-type and recombinant baculoviruses are becoming more attractive for the
      control of insect pests. Thus, there is an increased incentive to address and
      resolve logistical problems associated with large-scale production of these
      viruses. In this study, we have compared the potential of two insect cell lines,
      Tn5B1-4 and Sf21, for the production of polyhedra and compared the efficacy of
      both cell culture-derived and host-derived viruses by bioassay. The efficacy of
      both wild-type AcMNPV and AcAaIT, a recombinant baculovirus expressing an insect
      specific scorpion toxin, were compared. Yields of polyhedra from Tn5B1-4 were
      sixfold higher than those from the cell line Sf21. Morphological analysis of
      polyhedra derived from cell culture showed greater variability in size relative
      to host-derived polyhedra. The maximum size of cell culture-derived polyhedra was
      over 1.5 times larger than that of insect-derived polyhedra. The efficacy of
      AcMNPV and AcAaIT derived from cell culture, or from amplification in larvae of
      Trichoplusia ni or Heliothis virescens, was compared by bioassay in H. virescens.
      There was a significant difference between the slopes for lethal time data for
      host-derived and cell culture-derived wild-type virus. Mortality occurred at a
      faster rate following infection with host-derived virus. No significant
      difference was seen for the recombinant virus AcAaIT. Lethal doses of cell- and
      host-derived polyhedra were not significantly different. The reasons for and
      implications of this for pest control are discussed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8568279
TI  - Biocontrol potential of the entomogenous fungi Beauveria bassiana and Metarhizium
      anisopliae for tsetse flies (Glossina spp.) at developmental sites.
AB  - Spores of two entomogenous fungi, Beauveria bassiana and Metarhizium anisopliae,
      were mixed with sterile sand at two different concentrations (1.0 and 0.5
      g/liter) and larvae of tsetse flies Glossina morsitans morsitans allowed to
      pupate in it, simulating field larviposition sites. One gram weight of B.
      bassiana-sand mixture was estimated to contain 1.4 x 10(6) spores/g and that of
      M. anisopliae-sand mixture 2.3 x 10(6) spores/g. Adult tsetse emerging from pupae
      in sand-spore mixtures suffered heavy mortalities 2-10 days postemergence. The
      highest mortality recorded at 1.0 g/liter was 97% for B. bassiana and 80% for M.
      anisopliae. Lower spore concentrations produced lower mortalities. Possibilities
      of biocontrol of tsetse in the field using mycopesticides at breeding sites are
      discussed.

PMID- 8568280
TI  - Characterization of baculovirus insecticides expressing tailored Bacillus
      thuringiensis CryIA(b) crystal proteins.
AB  - Full-length, truncated, and mature forms of the CryIA(b) insecticidal crystal
      protein gene of Bacillus thuringiensis were engineered into the p10 locus of
      Autographa californica nuclear polyhdrosis virus (AcNPV). A signal sequence of
      Heliothis virescens juvenile hormone esterase was introduced at the N-terminus of
      these constructs to induce secretion. All recombinants, except those containing
      the mature toxin, produced high levels of CryIA(b) ICPs in insect cells. Thirty
      percent of the intracellular protoxin was N-glycosylated, suggesting that the
      protoxin was translocated across the ER membrane. Secretion into the medium,
      however, was limited. The production of the mature toxin was poor as a result of
      its cytotoxicity to insect cells. In a bioassay against second instar Spodoptera
      exigua larvae, using a recombinant expressing the Androctonus australis scorpion
      toxin gene in the same p10 locus as a positive control, the median survival time
      of AcNPV recombinants expressing the various B. thuringiensis CryIA(b) ICP
      constructs was not significant different from that of wild-type AcNPV. This
      suggests that production and/or secretion of B. thuringiensis (pro)toxins by
      AcNPV p10 recombinant viruses does not increase insecticidal activity since (i)
      the protoxins produced are inactive and not likely to be activated in vivo; (ii)
      secretion of the B. thuringiensis protoxins is poor; and (iii) production of the
      mature toxins results in cytotoxicity.

PMID- 8568281
TI  - Characterization of an iridescent virus isolated from the velvetbean caterpillar,
      Anticarsia gemmatalis.
AB  - An insect iridescent virus has been isolated from diseased velvetbean
      caterpillars, Anticarsia gemmatalis, found in Argentina. The cytopathology is
      similar to that reported for other iridescent viruses with infected larvae
      exhibiting blue-purple opalescence. Icosahedral particles (n = 119) purified by
      sucrose gradient rate zonal centrifugation had dimensions of 145 +/- 7 nm (point
      to-point) and 136 +/- 12 nm (side-to-side). The sedimentation coefficient was
      2250 +/- 10 S20,w when the virus was suspended in phosphate buffer.
      Characterization of proteins by SDS-polyacrylamide gel electrophoresis revealed
      24 polypeptides with a single major species of 53.6 kDa. Purified viral DNA had a
      density of 1.6902 g cm-3 in equilibrium ultracentrifugation, corresponding to a
      guanine:cytosine content of 32.2%. Analysis of digests of this DNA with two
      restriction enzymes revealed an average molecular size of 181.8 +/- 5.6 kbp. A
      499-bp fragment was amplified from the genome of this isolate using the
      polymerase chain reaction and then sequenced; data suggest this virus is very
      closely related to IV 1, originally isolated from Tipula paludosa. These
      properties indicate this virus is an isolate of the genus Iridovirus.

PMID- 8568282
TI  - Lectin binding to extracellularly melanized microfilariae of Brugia malayi from
      the hemocoel of Anopheles quadrimaculatus.
AB  - Binding patterns of fluorescein isothiocyanate (FITC)- and gold-conjugated
      lectins to extracellularly melanized sheathed and exsheathed microfilariae of
      subperiodic Brugia malayi, isolated from and in situ in the abdominal hemocoel of
      Anopheles quadrimaculatus 72-hr postinfection, were examined. Five FITC
      conjugated lectins [Helix pomatia agglutinin (HPA), Arachis hypogaea (peanut
      agglutinin-PNA), Triticum vulgaris (wheat germ agglutinin-WGA), Lens culinaris
      (lentil-LCH), and Concanavalin A (Con A)] with specificities for different
      carbohydrate moieties were tested for binding to isolated melanized microfilariae
      and observed with transmitted light and fluorescence microscopy. All five FITC
      lectins bound strongly to the acellular material accompanying the melanin
      deposits on the surface of isolated melanized microfilariae. Significant
      inhibition of FITC-lectin binding occurred when lectins were preincubated with
      their complementary carbohydrates before testing. H. pomatia agglutinin binding
      was totally inhibited by N-acetyl-D-glucosamine and N-acetyl-D-galactosamine.
      Other lectins were partially inhibited, such as PNA by galactose and lactose; WGA
      by N-acetylneuraminic acid; LCH by N-acetyl-D-glucosamine, mannose, glucose, and
      methyl alpha-D-mannopyranoside; and Con A by mannose and methyl alpha-D
      mannopyranoside. Three gold-conjugated lectins (HPA, PNA, and Con A), examined by
      using transmission electron microscopy, bound to the outer surface of the
      acellular material associated with the melanin deposits on isolated melanized
      microfilarial sheaths and melanized microfilariae and to the remnants of lysed
      hemocytes found in the proximity of the melanized deposits. Con A in the presence
      of gold-labeled horseradish peroxidase, examined by using transmission electron
      microscopy, showed random binding within the melanized capsule formed around the
      microfilarial sheath in situ. These results indicate that the acellular material
      accompanying melanin deposits on melanized microfilarial sheaths and sheathed and
      exsheathed microfilariae contain several glycoconjugates with exposed
      carbohydrate moieties and are possibly glycoproteins. These glycoproteins could
      be the by-products of the activation of the prophenoloxidase by the
      microfilariae.

PMID- 8568283
TI  - In vivo chemoactivation of oyster hemocytes induced by bacterial secretion
      products.
AB  - Movements of tissue hemocytes in the Eastern oyster Crassostrea virginica were
      monitored and quantified by image analysis of sections following inoculation with
      agar cores containing Escherichia coli or cell-free medium on which the bacteria
      had previously grown. Hemocytes respond to the presence of live bacteria by
      accumulating in widely dispersed areas of tissue surrounding the gut and
      digestive diverticula. The response is rapid and evident within 40 min, is
      maximal at 1 hr, and declines by 3 hr after inoculation. Sterile implanted agar
      cores do not produce a response. Bacteria killed with ozone elicit a response
      when inoculated together with the medium on which they had grown while bacteria
      killed by heat or formalin do not. Killed bacteria suspended in saline fail to
      stimulate hemocyte chemokinesis. Cell-free medium applied externally produces a
      response equal to that measured with live bacteria inoculated internally.
      Extraction of bacteria-free medium with hexane does not significantly reduce
      hemocyte chemokinesis. Digestion of bacteria-free medium with pronase completely
      eliminates chemokinesis. Molecular filtrates of bacteria-free medium induce
      maximal chemokinetic response at molecular weight as low as 1 kDa. These data
      show that the oyster hemocyte activators produced by E. coli are most likely low
      molecular-weight polypeptides which diffuse from the site of inoculation and can
      pass through the intact external surface epithelium to induce a chemokinetic
      response.

PMID- 8568284
TI  - Genetic transformation of an entomopathogenic nematode by microinjection.
AB  - We report the first successful transformation of an entomopathogenic nematode.
      Foreign genes were introduced in Heterorhabditis bacteriophora HP88 by
      microinjection using vectors carrying the Caenorhabditis elegans genes coding for
      the roller phenotype and 16-kDa heat shock protein (hsp16) gene. A translational
      fusion made by inserting lacZ in frame into hsp16 was expressed in the body
      musculature, hypodermis, and pharyngeal muscles. The transcription of the
      hsp16/lacZ transgenes resulted in the rapid synthesis of detectable levels of
      beta-galactosidase. This research opens new avenues for genetic modification of
      entomopathogenic nematodes.

PMID- 8568285
TI  - Infection of Aedes albopictus (Diptera: Culicidae) and Ae. aegypti with
      Lambornella stegomyiae (Ciliophora: Tetrahymenidae).
AB  - The transformation of Lambornella stegomyiae trophonts to theronts, the
      distribution of invasion cysts on larval Aedes albopictus cuticle, and the
      virulence of L. stegomyiae to Ae. albopictus and Aedes aegypti were studied in
      the laboratory. Transformation of trophonts into theronts was induced by a
      morphogenic agent released from larval Ae. albopictus homogenate. The first
      transformation was observed 4 hr after exposure to larval mosquito homogenate,
      but most transformations occurred between 12 and 16 hr. Distribution of invasion
      cysts on the cuticle of mosquito larvae was not uniform and most cysts were
      formed on the abdomen and head. L. stegomyiae was highly infective and virulent
      to Ae. albopictus (mortality rate: 99.53%) and Ae. aegypti (mortality rate:
      90.83%) larvae.

PMID- 8568286
TI  - Effects of influenza A nucleoprotein on polymorphonuclear neutrophil function.
AB  - Infection with influenza virus is commonly associated with polymorphonuclear
      neutrophil (PMNL) dysfunction and consequent secondary bacterial pneumonia. A
      recently isolated human-derived protein that inhibits PMNL chemotaxis and oxidant
      production shows a striking homology to the influenza A nucleoprotein. In the
      present study, the effects of purified influenza A nucleoprotein on PMNL
      chemotaxis, oxidant production, degranulation, and calcium homeostasis were
      studied. Results of the study demonstrate that purified nucleoprotein inhibits
      PMNL chemotaxis as well as superoxide production. In addition, purified
      nucleoprotein induces a rise in PMNL cytosolic calcium concentration in a manner
      similar to that demonstrated for crude influenza A lysates. In contrast, no
      difference in FMLP-stimulated PMNL elastase or beta glucuronidase release was
      noted after exposure to nucleoprotein. These studies suggest that the influenza A
      nucleoprotein may account for some of the neutrophil defect associated with
      cellular infection by this virus.

PMID- 8568287
TI  - Induction of mucosal antibodies by live attenuated and inactivated influenza
      virus vaccines in the chronically ill elderly.
AB  - Induction of local antibody responses to influenza A virus hemagglutinin by
      coadministration of two vaccines was investigated. Fifty elderly nursing home
      residents received inactivated trivalent influenza virus vaccine intramuscularly
      and simultaneously were randomized to receive either bivalent live attenuated
      influenza A virus vaccine or saline placebo intranasally in a blinded fashion.
      More significant increases in anti-H1 and -H3 IgA antibodies were detectable in
      nasal wash specimens of subjects who received live attenuated virus vaccine than
      in those who received intranasal placebo. The increased anti-hemagglutinin IgA
      antibody response was of longer duration in recipients of live attenuated
      vaccine. The change in antibody titers after vaccination was positively
      correlated with total blood lymphocyte counts measured before vaccination in both
      vaccinee groups (P < .05). There was a possible advantage of administering live
      attenuated with inactivated virus vaccines because of enhanced local antibody
      responses.

PMID- 8568288
TI  - Differential effects of famciclovir and valaciclovir on the pathogenesis of
      herpes simplex virus in a murine infection model including reactivation from
      latency.
AB  - The ability of famciclovir and valaciclovir to affect the establishment and
      maintenance of latency in mice with a cutaneous herpes simplex type 1 (HSV-1)
      infection was examined. Mice were treated via drinking water starting at various
      times between days 1 and 5 and terminating on day 10 after inoculation. Clinical
      signs and viral replication in the target tissues were monitored. Three to four
      months later, trigeminal and dorsal root ganglia were explanted from groups of 16
      mice and examined for latent virus by cocultivation. The two compounds differed
      in their effects on the acute neural infection, and ganglia explanted from
      famciclovir-treated mice were markedly reduced in their ability to reactivate
      virus, although neither drug affected latency if treatment was delayed for
      several months. The difference between the compounds is likely to reflect
      differences in the metabolism of their respective products, penciclovir and
      acyclovir, in infected neurons.

PMID- 8568289
TI  - Patterns of immune responses to the host-encoded GOR and hepatitis C virus core
      derived epitopes with relation to hepatitis C viremia, genotypes, and liver
      disease severity.
AB  - Antibody responses to the GOR epitope and hepatitis C virus (HCV) core were
      investigated in 136 patients with chronic HCV infection. Patient age (P = .011)
      and necroinflammatory activity (P < .001) were significantly greater in 92
      (67.6%) patients with anti-GOR than in 44 (32.4%) patients without anti-GOR. HCV
      RNA concentration was significantly higher in patients with anti-GOR (P = .031).
      HCV 1a or 1b genotypes were also found according to anti-GOR status. GOR and HCV
      core (amino acids 5-19) antibody responses correlated significantly (rs = .615, P
      < .001). Anti-HCV core(5-19) was detected in 67 (73%) of 92 patients with and in
      14 (32%) of 44 without anti-GOR (P < .001). Patients with concurrent anti-GOR and
      anti-HCV core(5-19) had significantly greater necroinflammatory activity (P =
      .003). By multivariate analysis, anti-HCV core(5-19), patient age, and
      necroinflammatory activity were correlated with anti-GOR response (P < .001).
      Reactivity to the GOR autoepitope correlates with HCV core response and liver
      necroinflammatory activity, thus suggesting an immunopathogenic role in chronic
      hepatitis C.

PMID- 8568290
TI  - Concurrent oral poliovirus and rhesus-human reassortant rotavirus vaccination:
      effects on immune responses to both vaccines and on efficacy of rotavirus
      vaccines. The US Rotavirus Vaccine Efficacy Group.
AB  - Interference between oral poliovirus vaccine (OPV) and monovalent (RRV-S1) and
      tetravalent (RRV-TV) rhesus-human rotavirus vaccines was evaluated. Serum
      antibody responses to OPV and rotavirus vaccines and efficacy of rotavirus
      vaccines were compared among control and vaccine groups stratified by number of
      concurrent OPV and rotavirus vaccinations received. Neutralizing antibody titers
      to poliovirus type 1 tended to rise more steeply in placebo than RRV-TV
      recipients, but there were no significant differences in seroprevalence or in
      geometric mean titers (GMTs) of antibodies to types 1, 2, or 3 among groups.
      Concurrent OPV resulted in lower IgA GMTs to rotavirus in RRV-S1 but not RRV-TV
      recipients. Rotavirus gastroenteritis rates among rotavirus vaccines did not
      differ by number of concurrent OPV doses received, but the sample sizes were too
      small to rule out any effect. These results suggest OPV and rhesus-human
      rotavirus vaccines may be given at the same visit in the United States.

PMID- 8568291
TI  - Protection against papillomavirus with a polynucleotide vaccine.
AB  - Genital infections with human papillomavirus (HPV) are increasingly recognized as
      a significant source of human disease; HPV is now implicated in up to 90% of
      cervical carcinomas. Neutralizing antibodies against papillomaviruses recognize
      conformational epitopes formed when viral capsid proteins assemble into virions
      or virus-like particles. Immunization with plasmid DNA encoding the major viral
      capsid protein L1 was studied as a means of inducing neutralizing antibodies and
      protection against virus challenge. In a cottontail rabbit papillomavirus (CRPV)
      model, immunization with plasmid DNA encoding L1 elicited conformationally
      specific neutralizing antibodies and provided immunity against papilloma
      formation upon challenge with CRPV. Immunization with DNA encoding the capsid
      protein may provide a means of protecting humans against HPV and would simplify
      the production of multivalent vaccines by combining plasmids that encode the
      viral capsid proteins of different strains. This may be of importance given the
      multiplicity of HPV types capable of causing disease.

PMID- 8568292
TI  - Alterations in the immune response of human immunodeficiency virus (HIV)-infected
      subjects treated with an HIV-specific protease inhibitor, ritonavir.
AB  - Effects of a human immunodeficiency virus (HIV) type 1 protease inhibitor,
      ritonavir, were evaluated in 21 patients enrolled in a phase I/II study. The
      magnitude and rates of CD4 and CD8 lymphocyte increase, changes in subsets of CD4
      and CD8 lymphocytes, and proliferative responses to mitogen and antigens were
      analyzed. Significant increases were noted in CD4 and CD8 lymphocyte counts;
      numbers of CD4CD45RO lymphocytes increased significantly by week 1 of therapy.
      Increases in the CD4CD45RA subset were observed at week 4. Reductions in the
      percentage of CD4 and CD8 lymphocytes expressing CD38 were noted. Increases in
      proliferative responses to phytohemagglutinin were noted in 6 of 7 patients and
      correlated with duration of virus load suppression. Increased responses to recall
      antigens and to HIV-specific proteins were observed. Treatment with ritonavir
      produced alterations in the immune system that included changes in T cell subset
      distribution and increases in CD4 and CD8 lymphocyte numbers and of lymphocyte
      function.

PMID- 8568293
TI  - A dose-ranging study of a prototype synthetic HIV-1MN V3 branched peptide
      vaccine. The National Institute of Allergy and Infectious Diseases AIDS Vaccine
      Evaluation Group.
AB  - A phase I double-blind trial was done to examine the safety and immunogenicity of
      a prototype synthetic human immunodeficiency virus type 1 MN strain (HIV-1MN)
      third variable region domain (V3) branched peptide vaccine in HIV-1-uninfected
      healthy adult volunteers. Subjects were randomly assigned to receive 20, 100, or
      500 micrograms of vaccine or alum adjuvant control on days 0, 28, and 168. The
      vaccine was well-tolerated and appeared safe. Induction of binding antibody to V3
      MN branched peptide was vaccine dose-related and was detectable in 9 of 10
      subjects in the highest-vaccine-dose group. HIV-1MN-neutralizing antibody was
      detected after the third 500-micrograms dose in 8 of 10 subjects at the 90%
      neutralization end point. V3 MN peptide stimulated lymphocyte proliferation in 15
      (75%) of 20 subjects after vaccination. In conclusion, this prototype vaccine was
      safe and it induced humoral and cell-mediated immune responses.

PMID- 8568294
TI  - Immunization with envelope subunit vaccine products elicits neutralizing
      antibodies against laboratory-adapted but not primary isolates of human
      immunodeficiency virus type 1. The National Institute of Allergy and Infectious
      Diseases AIDS Vaccine Evaluation Group.
AB  - Phase I studies of volunteers not infected with human immunodeficiency virus type
      1 (HIV-1) have shown that immunization with envelope subunit vaccine products
      elicits antibodies that neutralize laboratory-adapted (prototype) HIV-1 strains
      in vitro. Prototype strains are adapted to grow in continuous (neoplastic) cell
      lines and are more susceptible to neutralization than are primary isolates
      cultured in human peripheral blood mononuclear cells. In this study, 50 sera from
      nine phase I vaccine trials and 16 from HIV-1-infected persons were evaluated for
      neutralizing antibody activity against 3 laboratory-adapted and 5 primary HIV-1
      isolates. Of 50 sera, 49 neutralized at least 1 of the prototype strains;
      however, none displayed neutralizing activity against primary isolates of HIV-1.
      Serum from most HIV-1-infected persons neutralized both laboratory-adapted and
      primary HIV-1 isolates. These data demonstrate a qualitative, or large
      quantitative, difference in the neutralizing antibody response induced by
      envelope subunit vaccination and natural HIV-1 infection.

PMID- 8568295
TI  - Relation between changes in cellular load, evolution of viral phenotype, and the
      clonal composition of virus populations in the course of human immunodeficiency
      virus type 1 infection.
AB  - The relationship between the evolution of human immunodeficiency virus type 1
      (HIV-1) biologic phenotype, changes in the proportion of infected peripheral
      blood mononuclear cells, and the relative contribution of non-syncytium-inducing
      (NSI) and syncytium-inducing (SI) HIV-1 variants to virus load was studied during
      the course of HIV-1 infection. In 65 HIV-1-infected subjects, the proportion of
      infected CD4 T cells was higher in persons who carried SI variants. Longitudinal
      studies revealed that the emergence of SI HIV-1 variants can occur at relatively
      low numbers of HIV-1-infected cells. Emergence of SI variants frequently
      coincided with an increase of virus load due to an expansion of both NSI and SI
      variants, although the contribution of SI viruses to the total virus population
      significantly increased with time after SI phenotype conversion. These data
      indicate that NSI to SI phenotype conversion, rather than resulting from high
      virus load, is part of the sequence of events that leads to increased virus load
      and CD4 cell depletion.

PMID- 8568296
TI  - Lamivudine or stavudine in two- and three-drug combinations against human
      immunodeficiency virus type 1 replication in vitro.
AB  - Two- and three-drug combinations of lamivudine or stavudine with other
      antiretroviral drugs were evaluated for activity against human immunodeficiency
      virus type 1 (HIV-1) activity in peripheral blood mononuclear cells. Other agents
      included zidovudine, didanosine, nevirapine, and saquinavir. Paired zidovudine
      sensitive and -resistant clinical HIV-1 isolates were used. Additive or
      synergistic interactions were observed against the zidovudine-sensitive isolate
      with the following combinations: lamivudine-zidovudine, lamivudine-stavudine,
      lamivudine-saquinavir, lamivudine-nevirapine, stavudine-zidovudine, stavudine
      didanosine, stavudine-saquinavir, stavudine-nevirapine, lamivudine-zidovudine
      saquinavir, lamivudine-zidovudine-stavudine, stavudine-zidovudine-nevirapine,
      lamivudine-zidovudine-nevirapine, and stavudine-zidovudine-saquinavir. Against
      the zidovudine-resistant isolate, additive or synergistic interactions were seen
      with most two- and three-drug combinations, but the combination of stavudine
      zidovudine was antagonistic. The clinical implications of these in vitro
      observations should be explored.

PMID- 8568297
TI  - Invasive group B streptococcal disease: the emergence of serotype V.
AB  - Group B streptococci (GBS) cause invasive disease in neonates, pregnant adults,
      and nonpregnant adults with underlying or chronic disease. Previous studies found
      capsular serotypes Ia, Ib, II, and III cause invasive disease. Prospective
      population-based surveillance of invasive GBS disease was done from June 1992 to
      June 1993 in metropolitan Atlanta: 279 patients had invasive disease. Of these,
      43% were < or = 6 months old, and 57% were adults. The incidence among all adults
      was 7.7/100,000/year, 33% higher than in 1989-1990 (P < .01). The incidence in
      nonpregnant adults was 5.9/100,000/year, 37% higher than in 1989-1990 (P < .02).
      Serotyping of 178 patient isolates revealed that 34% had GBS serotype Ia or Ia/c,
      8% had Ib/c, 6% had II or II/c, 29% had III, 0% had IV, 21% had V, and 2% were
      nontypeable. Serotype V was recovered from all groups and was the most common
      serotype from nonpregnant adults. Serotype V isolates appeared to be highly
      related genetically. The increasing incidence of GBS disease in adults, the
      changing distribution of serotypes, and the emergence of serotype V will impact
      vaccine strategies.

PMID- 8568298
TI  - Spread of multidrug-resistant Streptococcus pneumoniae among hospitalized
      children in Slovakia.
AB  - A multidrug-resistant serotype 14 strain of Streptococcus pneumoniae was isolated
      from sterile-site specimens and nasopharyngeal secretions from > 200 children in
      Slovakia between 1985 and 1990. Nasopharyngeal culture surveys were done to
      determine the extent of spread and means of transmission of this strain. The
      resistant strain was isolated from cultures of 8 (33.0%) of 24 children at
      hospital A and from 1 (0.8%) of 130 children attending outpatient clinics or day
      care centers (P < .001). One-quarter of the initially uncolonized children at
      hospital A acquired the resistant strain during hospitalization. Among
      hospitalized children, frequent antimicrobial drug use (P < .01), prior
      hospitalization (P < .005), and length of hospital stay (P < .001) were
      associated with infection with the resistant strain. These findings support
      limiting broad-spectrum antimicrobial drug use and nonessential hospitalizations
      in settings were drug-resistant pneumococci are prevalent. Development of a
      pneumococcal vaccine that is immunogenic in young children is urgently needed.

PMID- 8568299
TI  - Truncated Streptococcus pneumoniae PspA molecules elicit cross-protective
      immunity against pneumococcal challenge in mice.
AB  - Immunization with pneumococcal surface protein A (PspA) from Streptococcus
      pneumoniae strain Rx1 cross-protects mice against challenge with diverse
      pneumococci. Truncated Rx1 PspA, consisting of amino acids 192-588, elicits
      protection against the mouse-virulent strain WU2. The possibility that homologous
      regions of other PspAs could also elicit cross-protection was investigated.
      Oligonucleotide primers designed according to the Rx1 pspA gene sequence were
      used to amplify chromosomal DNA from 15 diverse pneumococci. Three recombinant
      PspAs were evaluated for their ability to elicit protection in mice against
      challenge with 7 strains representing capsular types 3, 4, 5, 6A, and 6B. Two of
      the three truncated PspAs each elicited cross-protection against 71%-100% of the
      S. pneumoniae challenge strains examined. These data suggest that this technique
      may be useful for the generation of diverse PspAs for inclusion in a broadly
      protective pneumococcal vaccine.

PMID- 8568300
TI  - Antibody response to pneumococcal capsular polysaccharide vaccine in the elderly.
AB  - Antibody response to 23-valent pneumococcal vaccine was assessed in 350 subjects
      (131 men, 219 women) aged 65-91 years. IgG antibodies to pneumococcal serotypes
      4, 6B, 9V, 14, 19F, and 23F were measured by EIA after blocking of antibodies to
      cell wall polysaccharide. Antibody concentrations in both pre- and
      postvaccination sera (mean interval, 35 days) were higher in elderly men than
      women; in the women, the concentrations decreased significantly with increasing
      age, but not in the men. Antibody fold increases were good in the elderly,
      including those > or = 85 years old. The overall percentage of the elderly with
      antibody concentrations > 1 microgram/mL to the 6 antigens increased by
      vaccination from 61% to 87%, but in the women > or = 85 years old, only to 75%.
      Antibody response to 23-valent pneumococcal vaccine was satisfactory in the
      elderly.

PMID- 8568301
TI  - Haemophilus ducreyi elicits a cutaneous infiltrate of CD4 cells during
      experimental human infection.
AB  - Human subjects were experimentally infected with Haemophilus ducreyi for up to 2
      weeks. Bacterial suspensions were delivered into the epidermis and dermis through
      puncture wounds made by an allergy-testing device. Subjects developed papular
      lesions that evolved into pustules resembling natural disease. Some papular
      lesions resolved spontaneously, indicating that host responses may clear
      infection. Bacteria were shed intermittently from lesions, suggesting that H.
      ducreyi may be transmissible before ulceration. Host responses to infection
      consisted primarily of cutaneous infiltrate of polymorphonuclear leukocytes,
      Langerhans cells, macrophages, and CD4 T cells of alpha beta lineage. Expression
      of HLA-DR by keratinocytes was associated with the presence of interferon-gamma
      mRNA in the skin. There was little evidence for humoral or peripheral blood
      mononuclear cell responses to bacterial antigens. The cutaneous infiltrate of CD4
      cells and macrophages provides a mechanism that facilitates transmission of human
      immunodeficiency virus by H. ducreyi.

PMID- 8568302
TI  - Identification of an uncultivable Borrelia species in the hard tick Amblyomma
      americanum: possible agent of a Lyme disease-like illness.
AB  - Bites from the hard tick Amblyomma americanum are associated with a Lyme disease
      like illness in the southern United States. To identify possible etiologic agents
      for this disorder, A. americanum ticks were collected in Missouri, Texas, New
      Jersey, and New York and examined microscopically. Uncultivable spirochetes were
      present in approximately 2% of the ticks. Borrelia genus-specific
      oligonucleotides for the flagellin and 16S rRNA genes were used for amplification
      of DNA. Products were obtained from ticks containing spirochetes by microscopy
      but not from spirochete-negative ticks. Sequences of partial genes from
      spirochetes in Texas and New Jersey ticks differed by only 2 of 641 nucleotides
      for flagellin and 2 of 1336 nucleotides for 16S rRNA. Phylogenetic analysis
      showed that the spirochete was a Borrelia species distinct from previously
      characterized members of this genus, including Borrelia burgdorferi. Gene
      amplification could be used to detect these spirochetes in ticks and possible
      mammalian hosts.

PMID- 8568303
TI  - Evidence against a role for interleukin-10 in the regulation of growth of
      Mycobacterium avium in human monocytes.
AB  - Interleukin-10 (IL-10) inhibits intracellular Mycobacterium avium killing by
      cytokine-activated murine macrophages and may have a role in pathogenesis.
      Cytokine activities in supernatants of M. avium-infected human monocytes were
      maximal at 6-24 h for tumor necrosis factor (TNF)-alpha and 24-48 h for IL-10.
      TNF-alpha and IL-10 production increased with increasing M. avium-to-monocyte
      infection ratios (20:1 to 200:1). TNF-alpha production by monocytes infected with
      smooth, domed, and opaque organisms at 200:1 exceeded that of monocytes infected
      with smooth, flat, and transparent M. avium (P < .01). IL-10 induction
      demonstrated considerable strain-to-strain variability and did not correlate with
      intracellular M. avium growth. IL-10 significantly inhibited TNF-alpha, IL-1
      beta, and IL-6 production by M. avium-infected monocytes. Coculturing monocytes
      with IL-10 after M. avium infection did not affect intracellular M. avium growth.
      Differential induction of TNF-alpha may be a factor in the intracellular growth
      of M. avium in human monocytes. IL-10, however, played no apparent role in
      pathogenicity in this model.

PMID- 8568304
TI  - The broad-spectrum activity and efficacy of catheters coated with minocycline and
      rifampin.
AB  - The in vitro and in vivo activities of catheters coated with minocycline and
      rifampin and with chlorhexidine gluconate and silver sulfadiazine were evaluated.
      When incubated in serum at 37 degrees C, the half-life of the inhibitory activity
      of catheters coated with minocycline and rifampin was 25 days compared with 3
      days for catheters coated with chlorhexidine gluconate and silver sulfadiazine.
      In a rabbit model, catheters coated with minocycline and rifampin were
      significantly more efficacious than catheters coated with chlorhexidine and
      silver sulfadiazine in preventing colonization and infection with Staphylococcus
      aureus (P < .05). Catheters coated with minocycline and rifampin demonstrated
      broad-spectrum in vitro inhibitory activity against gram-positive bacteria, gram
      negative bacteria, and Candida albicans that was significantly superior to the
      inhibitory activity of catheters coated with chlorhexidine gluconate and silver
      sulfadiazine (P < .01). Minocycline and rifampin were also highly efficacious in
      preventing colonization and infection in vivo.

PMID- 8568305
TI  - A murine model of Candida glabrata vaginitis.
AB  - Vaginal Candida glabrata infections have increased significantly in recent years
      and are particularly common in women with uncontrolled diabetes mellitus. Efforts
      to understand the pathogenesis and treatment of this infection have been hindered
      by the lack of experimental animal models. Before onset of hyperglycemia,
      nonobese diabetic (NOD) mice inoculated intravaginally with clinical C. glabrata
      isolates were shown to support high vaginal titers of C. glabrata for > 14 days
      with evidence for superficial invasion of vaginal epithelial tissue. In contrast,
      congenic diabetic-resistant mice and mice susceptible to Candida albicans
      infections were significantly less susceptible to vaginal infection by C.
      glabrata, suggesting a potential link between the susceptibility of NOD mice to
      diabetes and their susceptibility to vaginal C. glabrata infections. This animal
      model of C. glabrata vaginitis provides a means to study the genetics and
      pathogenesis of C. glabrata infections and to evaluate the efficacy of
      antimycotic agents against C. glabrata.

PMID- 8568306
TI  - Nitric oxide and host defense against Pneumocystis carinii infection in a mouse
      model.
AB  - To investigate whether successful host defense against Pneumocystis carinii is
      dependent on induction of inducible nitric oxide synthase (iNOS) in alveolar
      macrophages, immunocompetent mice, mice depleted of CD4 lymphocytes with anti-CD4
      antibody, and mice with severe combined immunodeficiency (scid) were inoculated
      intratracheally with P. carinii. Three weeks later, immunocompetent mice had
      cleared the organisms completely, while CD4 cell-depleted and scid mice were
      severely infected (scores, 3.6 +/- 0.2 and 2.8 +/- 0.2, respectively).
      Inflammation scores were significantly higher in CD4 cell-depleted mice (3.4 +/-
      0.2) than in scid mice (0.6 +/- 0.2). Minimal iNOS mRNA was detectable in lung
      tissue from immunocompetent mice; iNOS mRNA was comparable in scid mice and mice
      inoculated with PBS but was 6-fold higher in CD4 cell-depleted mice.
      Immunohistochemistry localized iNOS protein to alveolar macrophages in CD4 cell
      depleted mice. Thus, iNOS is an unlikely participant in host defense against P.
      carinii, because enzyme expression does not correlate with either clearance or
      severity of infection.

PMID- 8568308
TI  - Prognostic significance and risk factors of untreated cytomegalovirus viremia in
      liver transplant recipients.
AB  - To study whether cytomegalovirus (CMV) viremia is a reliable marker of impending
      CMV disease and thus a guide for preemptive antiviral therapy, 126 consecutive
      liver transplant recipients were followed by routine CMV blood cultures in the
      absence of antiviral prophylaxis or treatment for viremia. Seventy-three patients
      (58%) developed CMV infections, and 36 (29%) had more than one infection episode:
      29 patients (23%) had organ involvement and 45 (36%) had viremia. Within a same
      episode, CMV viremia was 90% sensitive and 80% specific for predicting concurrent
      organ involvement but preceded organ involvement in only 9 (31%) of 29 patients.
      In a separate analysis, untreated isolated CMV viremia in the first CMV infection
      episode was followed by organ involvement in a subsequent episode in 9 (33%) of
      28 patients, mainly in the donor-positive, recipient-negative (D+/R-) population.
      The results indicate that CMV viremia is not an ideal marker to guide preemptive
      antiviral treatment in liver transplant recipients but is a good marker in D+/R-
      patients.

PMID- 8568307
TI  - Molecular phylogenetic analysis of Cyclospora, the human intestinal pathogen,
      suggests that it is closely related to Eimeria species.
AB  - A coccidian organism assigned to the genus Cyclospora has been increasingly
      recognized in association with prolonged diarrhea in humans throughout the world.
      Confusion surrounds the taxonomy of this fastidious organism, despite the
      availability of morphology and sporulation characteristics. The small subunit
      rRNA coding region from cyclosporan oocysts purified from a human fecal specimen
      was amplified and sequenced. The same sequence was present in specimens from 8
      other patients with cyclosporan oocysts but absent in specimens from asymptomatic
      subjects and from cryptosporidiosis patients. Phylogenetic analysis of rDNA
      sequences reveals that the human-associated Cyclospora is closely related to
      members of the Eimeria genus. These results allow predictions concerning
      Cyclospora host specificity, life cycle, and epidemiology as well as the
      development of a specific polymerase chain reaction-based diagnostic assay.

PMID- 8568309
TI  - The protective effect of immunologic boosting against zoster: an analysis in
      leukemic children who were vaccinated against chickenpox.
AB  - Whether reexposure of varicella-immune persons to varicella-zoster virus would
      protect against or predispose to development of zoster was analyzed. The rate of
      zoster in 511 leukemic recipients of varicella vaccine who had 1 or > 1 dose of
      varicella vaccine and in those who did or did not have a household exposure to
      varicella was determined. A Kaplan-Meier life-table analysis revealed that the
      incidence of zoster was lower in those given > 1 dose of vaccine (P < .05). A Cox
      proportional hazards analysis showed that both household exposure to varicella
      and receipt of > 1 dose of vaccine were highly protective (P < .01) against
      zoster. Thus, the risk of zoster is decreased by reexposure to varicella-zoster
      virus, either by vaccination or by close exposure to varicella.

PMID- 8568310
TI  - Comparison of US inactivated split-virus and Russian live attenuated, cold
      adapted trivalent influenza vaccines in Russian schoolchildren.
AB  - In a blinded, placebo-controlled study, the reactogenicity, immunogenicity, and
      clinical efficacy of single doses of US inactivated split-virus and Russian live
      attenuated, cold-adapted influenza vaccines were compared in 555 schoolchildren
      in Vologda, Russia. Serial serum samples were collected and school absenteeism
      was assessed. Systemic reactions were rare, but local reactions (primarily
      erythema at the injection site) were observed in 27% of the inactivated vaccine
      group, and coryza (12%) and sore throat (8%) were observed in the attenuated
      vaccine group. At 4 weeks after vaccination a > or = 4-fold rise in titer of
      hemagglutination inhibition antibody to A (H1N1), A (H3N2), and B was noted,
      respectively, among 78%, 88%, and 53% of children who received inactivated
      vaccine and among 55%, 79%, and 30% of children who received attenuated vaccine.
      The vaccine efficacy for preventing school absenteeism due to respiratory illness
      during the period of peak influenza activity was 56% for inactivated vaccine and
      47% for attenuated vaccine.

PMID- 8568311
TI  - Prevalence and type of precore hepatitis B virus mutants in hepatitis D virus
      superinfection and its clinical implications.
AB  - To study the prevalence and type of the hepatitis B e antigen (HBeAg)-negative
      mutant in hepatitis D virus (HDV) superinfection, the precore region of hepatitis
      B virus (HBV) was analyzed by cycle sequencing. Of the 58 samples sequenced, 24
      were wild type and 34 carried mutants. The precore stop mutation (TAG) at the
      28th codon was found in 32 cases, other mutations were found in 7, and double
      mutations were found in 5. The absence of HBeAg showed a substantial agreement
      with the presence of mutants (kappa value, 0.74). Of the acute hepatitis
      patients, HDV replication and clinical manifestations were not significantly
      different between those with mutant and wild type virus, except that those with
      mutant virus were older (mean age, 48 vs. 28 years; P < .002). The absence of
      HBeAg in these patients is mainly due to HDV superinfection in older HBV carriers
      who already had precore mutant.

PMID- 8568312
TI  - Lymphocyte subsets, apoptosis, and cytokines in patients with chronic fatigue
      syndrome.
AB  - Whether immunologic abnormalities correlate with fatigue severity and functional
      impairment in chronic fatigue syndrome (CFS) was investigated. Blood mononuclear
      cells were immunophenotyped and circulating ex vivo-produced cytokines were
      measured in 76 CFS patients and 69 healthy matched controls. Expression of CD11b
      on CD8 cells was significantly decreased in CFS patients. However, the previously
      reported increased expression of CD38 and HLA-DR was not confirmed. There was no
      obvious difference in apoptosis in leukocyte cultures, circulating cytokines, and
      ex vivo production of interleukin (IL)-1 alpha and IL-1 receptor antagonist.
      Endotoxin-stimulated ex vivo production of tumor necrosis factor-alpha and IL
      beta was significantly lower in CFS. The immunologic test results did not
      correlate with fatigue severity or psychologic well-being was measured by
      Checklist Individual Strength, Beck Depression Inventory, and Sickness Impact
      Profile. Thus, these immunologic tests cannot be used as diagnostic tools in
      individual CFS patients.

PMID- 8568313
TI  - Soluble tumor necrosis factor-alpha receptor type II (sTNF alpha RII) correlates
      with human immunodeficiency virus (HIV) RNA copy number in HIV-infected patients.
AB  - Soluble TNF receptor type II (sTNF alpha RII) levels in serum, CD4 lymphocyte
      counts, and human immunodeficiency virus (HIV) burdens have each been correlated
      with HIV disease progression. The level of sTNF alpha RII and HIV RNA was
      measured in serum and the CD4 lymphocyte count of 25 HIV-infected patients was
      determined. sTNF alpha RII ranged between 3.019 and 12.57 ng/mL (mean +/- SD,
      6.705 +/- 2.5). HIV-1 RNA varied from 960 to 281,160 copies/mL (71,988 +/-
      75,684). CD4 cell number was between 4 and 540/microL (181.3 +/- 152.2).
      Univariate analysis revealed a moderate inverse correlation of sTNF alpha RII
      with CD4 cell number (r = -.41, P < .05) and a strong positive correlation
      between sTNF alpha RII and log RNA copy number (r = .62, P < .001). On
      multivariate analysis, sTNF alpha RII strongly correlated with RNA copy number (P
      < .01) but not CD4 lymphocyte count. sTNF alpha RII measurements appear to be
      predictive of clinical outcomes because they are a surrogate indicator of the
      patients' immunologic response to a virus load.

PMID- 8568314
TI  - Relationship between infectious cell-associated human immunodeficiency virus type
      1 load, T lymphocyte subsets, and stage of infection in homosexual men.
AB  - The relationship between cell-associated infectious human immunodeficiency virus
      type 1 (HIV) load (infectious units/10(6) peripheral blood mononuclear cells
      [IUPM]) and phenotypes of CD4+ and CD8+ lymphocytes was studied. IUPM were
      measured in 242 HIV-infected homosexual men by quantitative microculture and T
      cell subsets by two-color flow cytometry. In multivariate analysis, IUPM
      correlated negatively with CD4+ lymphocyte level and with a diagnosis of AIDS and
      positively with the proportion of CD8+ lymphocytes expressing the activation
      marker CD38. After adjusting for level of CD4+ lymphocytes, men with AIDS had
      significantly lower IUPM than those without AIDS. The correlation between IUPM
      and CD4+ lymphocyte level was largely explained by correlation with level of CD4+
      lymphocytes with resting phenotypes (HLA-DR-, CD38-) rather than with those
      expressing HLA-DR and CD38. Thus, subsets of CD4+ lymphocytes may vary in cell
      associated infectious HIV content at different stages of HIV infection.

PMID- 8568315
TI  - Human immunodeficiency virus type 1 (HIV-1)-seronegative injection drug users at
      risk for HIV exposure have antibodies to HLA class I antigens and T cells
      specific for HIV envelope.
AB  - The question of whether persistently seronegative persons at high risk for human
      immunodeficiency virus type 1 (HIV-1) infection exhibit HIV-1-specific T cell
      responses and antibodies to HIV-1 envelope epitopes shared with selected HLAs was
      assessed. These antibodies are not detectable by conventional serologic methods.
      Envelope-specific helper T (Env-Th) cell responses and antibodies specific for
      the HIV/HLA epitopes were studied in 21 HIV-1-negative injection drug users
      (IDUs). HIV/HLA antibodies were detected in 7 (33.3%) of 21 IDUs and 4 (4.3%) of
      94 low-risk controls. Env-Th cell responses were detected in 16 (76.2%) of 21
      IDUs and in 2 (3.1%) of 65 low-risk controls. All HIV/HLA antibody-positive IDUs
      also had Env-Th cell responses. These findings confirm the presence of HIV-1
      specific immunity in conventionally seronegative individuals. Further
      characterization of these responses could provide the basis for new preventive
      strategies.

PMID- 8568316
TI  - Recognition of the highly conserved YMDD region in the human immunodeficiency
      virus type 1 reverse transcriptase by HLA-A2-restricted cytotoxic T lymphocytes
      from an asymptomatic long-term nonprogressor.
AB  - The human immunodeficiency virus (HIV) type 1 reverse transcriptase (RT) is an
      important target for therapeutic intervention and for HIV-1-specific cytotoxic T
      lymphocytes (CTL). An HLA-A2-restricted CTL epitope containing the sequence YMDD,
      which is highly conserved among human and animal retroviruses and essential for
      function of the RNA-dependent DNA polymerase, is identified. The drug resistance
      mutation at RT amino acid 184 (M184V), associated with (-)-2'-deoxy-3'
      thiacytidine (lamivudine), (-)-2'-deoxy-5-fluoro-3'-thiacytidine (FTC), and
      dideoxyinosine resistance, is located within this epitope and abolishes
      recognition by an established CTL response. This study demonstrates that the CTL
      response may target functionally relevant regions of the RT protein and suggests
      drug therapy may select for viral variants with altered susceptibility to
      established cellular immune responses.

PMID- 8568317
TI  - Meat grinders and molecular epidemiology: two supermarket outbreaks of
      Escherichia coli O157:H7 infection.
AB  - Between 23 June and 15 July 1994, 21 cases (19 primary and 2 secondary) of
      Escherichia coli O157:H7 infection were identified in the Bethel, Connecticut,
      area. Three pulsed-field gel electrophoresis (PFGE) patterns from 15 isolates (I,
      n = 13; II, n = 2; and III, n = 1) were observed. A case-control study that
      excluded secondary cases and patients with PFGE II and III patterns (n = 16)
      demonstrated that consumption of food from one supermarket was associated with
      illness (15/16 cases vs. 31/47 geographically matched controls, odds ratio [OR]
      undefined, lower 95% confidence interval OR = 1.45, P = .018). No one food was
      associated with illness. Inspection of the supermarket revealed deficiencies in
      hygiene and meat handling practices. The 2 cases with PFGE II ate raw beef and
      raw lamb from a second supermarket. These outbreaks demonstrate the value of PFGE
      in supporting epidemiologic investigations and the potential for outbreaks
      arising from retail outlets.

PMID- 8568318
TI  - Route of infection determines the clinical manifestations of acute Q fever.
AB  - In Nova Scotia the main manifestation of acute Q fever is pneumonia, while in
      France it is granulomatous hepatitis. To test the hypothesis that the route of
      infection is the major determinant of the manifestations of acute Q fever, 10
      groups of 10- to 12-g female BALB/c mice (4 animals/group) were used. Five groups
      were inoculated intraperitoneally (ip) and 5 intranasally (inl) with Coxiella
      burnetii. Both routes of infection resulted in pneumonia. However, the inl route
      resulted in greater airway changes (on a numeric scale with 0 being no changes):
      2.05 +/- 2.20 versus 0.60 +/- 0.83 (P < .002). The ip route resulted only in
      hepatosplenomegaly. It was concluded that the route of infection is one
      determinant of the manifestations of acute Q fever.

PMID- 8568320
TI  - Primary and secondary syphilis lesions contain mRNA for Th1 cytokines.
AB  - Phagocytosis of Treponema pallidum by cytokine-activated macrophages aids
      bacterial clearance and lesion resolution in early syphilis. To investigate the
      cytokine profiles of cells infiltrating primary and secondary syphilis lesions,
      reverse transcription and polymerase chain reaction (RT-PCR) were used to detect
      cytokine mRNA in 13 lesion biopsies. Both primary and secondary lesions contained
      mRNA encoding interleukin (IL)-2, interferon-gamma (IFN-gamma), IL-12p40, and IL
      10. In contrast to a lesion from a patient with recurrent herpes simplex virus
      type 2, no message for IL-4 could be detected in any of the syphilis lesions, and
      10 of 13 had no mRNA for IL-5 or IL-13. These findings are consistent with a Th1
      predominant local cellular response activating macrophages and support the
      hypothesis that IFN-gamma-activated macrophages are primary effectors in
      treponeme clearance.

PMID- 8568319
TI  - Effect of pregnancy on the risk of developing active tuberculosis.
AB  - In a case-control study, the effect of recent pregnancy on the risk of developing
      active tuberculosis among women of reproductive age was investigated in Santo
      Domingo. Human immunodeficiency virus (HIV)-positive and HIV-negative women
      diagnosed with new-onset tuberculosis (TB) were compared, respectively, with HIV
      positive and HIV-negative women without TB with regard to reproductive history,
      demographic characteristics, and risk factors for HIV infection. In neither HIV
      positive nor HIV-negative women was recent pregnancy or childbirth associated
      with an increased risk of developing active TB. These results fail to confirm
      earlier suggestions that pregnancy increases the risk that a woman of child
      bearing age infected with Mycobacterium tuberculosis will develop active TB.

PMID- 8568321
TI  - Silver iontophoretic catheter: a prototype of a long-term antiinfective vascular
      access device.
AB  - A silver iontophoretic catheter (SIC) was developed consisting of two
      electrically charged parallel silver wires helically wrapped around the proximal
      segment of a vascular catheter. In vitro and in vivo activities of this catheter
      were compared with those of an aseptic catheter coated with chlorhexidine and
      silver sulfadiazine (CH/SS). The SIC demonstrated broad-spectrum in vitro
      inhibitory activity against bacteria and Candida albicans comparable to that of
      the CH/SS-coated catheter. The durability of activity was determined by
      incubating catheters in serum at 37 degrees C for various time intervals. After
      30 days, the antimicrobial activity of the SIC did not change significantly,
      while that of the CH/SS-coated catheter was reduced to a suboptimal level. In a
      rabbit model, the SIC was safe and significantly more efficacious than the CH/SS
      coated catheter in preventing colonization with Staphylococcus aureus (P < .05).
      The SIC has broad-spectrum inhibitory activity of long durability and is highly
      efficacious in preventing colonization in vivo.

PMID- 8568322
TI  - Cerebrospinal fluid antibodies detected by ELISA against a 33-kDa antigen from
      spherules of Coccidioides immitis in patients with coccidioidal meningitis. The
      National Institute of Allergy and Infectious Diseases Mycoses Study Group.
AB  - Antibodies against a 33-kDa antigen from Coccidioides immitis were detected by
      ELISA in patients' cerebrospinal fluid (CSF). Anti-33-kDa antibodies were
      detected at dilutions > 1:80 in only 1 (1.4%) of 73 patients without coccidioidal
      meningitis but in 74 (71.8%) of 103 with meningitis. Anti-33-kDa antibodies were
      detected in 53 (91.4%) of 58 patients whose anti-coccidioidal complement-fixing
      (CF) antibodies were detectable and in 21 (46.7%) of 45 patients whose CSF was
      negative by CF test (positive predictive value, 99%; negative predictive value,
      71%; sensitivity, 72%; specificity, 99%). Anti-33-kDa antibodies, among which
      IgG1 was the dominant subclass, increased when infections worsened and decreased
      when patients' conditions improved. Antibody concentration appeared to be
      independent of most baseline findings, although only 1 of 5 patients coinfected
      with human immunodeficiency virus had initially detectable antibodies.
      Measurement of anti-33-kDa antibodies is a sensitive indicator of coccidioidal
      meningitis and of its clinical course.

PMID- 8568323
TI  - Human cytomegalovirus infection of leukocyte populations.

PMID- 8568324
TI  - Acyclovir in human immunodeficiency virus patients.

PMID- 8568325
TI  - Inflammation in human immunodeficiency virus type 1 infection as a cause of
      decreased plasma retinol.

PMID- 8568326
TI  - Hepatitis C virus genotypes in different risk populations in Spain. The Hepatitis
      HIV Spanish Study Group.

PMID- 8568327
TI  - Immunologic mechanism for human immunodeficiency virus type 1 gp120 vaccine
      failure.

PMID- 8568328
TI  - Analysis of naturally occurring antibodies to mucoid Pseudomonas aeruginosa in
      cystic fibrosis patients.

PMID- 8568329
TI  - Pancreas transplantation.

PMID- 8568330
TI  - Overexpression of HER2/neu oncogene in pancreatic cancer correlates with
      shortened survival.
AB  - For the purpose of determining the prognostic significance of HER2/neu oncogene
      in pancreatic and ampullary cancers, 21 pancreatic cancers of ductal origin and
      six cancers of the ampulla of Vater were studied immunohistochemically using the
      monoclonal antibody (MAb) CB11, specifically reactive with HER2/neu product.
      Staining of the epithelium of the normal duct and acini was negative or weakly
      positive. Moderately and strongly positive reactions indicated the overexpression
      of this gene, and were found in 10 of 21 (47.6%) pancreatic cancers of ductal
      origin and in 2 of 6 (33.3%) ampullary adenocarcinomas. Overexpression of
      HER2/neu was closely and inversely related to the survival of the patients with
      pancreatic cancer of ductal origin: 19.1 +/- 11.7 mo for those not overexpressing
      vs 7.3 +/- 3.8 mo for the overexpressors (p < 0.01). Among the pancreatic cancer
      group, 11 patients underwent cancer resection. The average survival for the 7
      with nonoverexpressing cancer was 21.4 +/- 14.3 mo vs 10.5 +/- 3.6 mo for those
      with overexpressing tumor. Among those not undergoing resection, the average
      survival for the 4 with nonoverexpressing cancer was 15.0 +/- 3.8 mo as
      contrasted to 5.2 +/- 2.1 mo for the overexpressors (p < 0.01). Although the
      number of patients is small, these findings suggest that the overexpression of
      HER2/neu gene product may be frequently found in pancreatic cancer of ductal
      origin and may be one of the useful prognostic biomarkers for this cancer.

PMID- 8568331
TI  - Fusion and duplication variants of pancreatic duct system. Clinical and
      pancreatographic evaluation.
AB  - The aim of this study was to assess the incidence of fusion and duplication
      variants of the pancreatic duct system and their clinical significance. A total
      of 650 endoscopic retrograde cholangiopancreatography were reviewed; 485 cases
      with satisfactory imaging of the pancreatic ducts were included in the study.
      Anatomic variants were observed in 48 patients (9.9%), fusion variants were 54.1%
      of the cases (22 pancreas divisum and 4 functional divisum), and duplication
      variants were 45.8% (13 bifurcations of the main pancreatic duct, 4 loop, 2N
      shape, 3 ring). Clinical indications to endoscopic cholangiopancreatography were
      idiopathic acute pancreatitis (33.3%), suspected chronic pancreatitis (18.7%),
      unexplained abdominal pain (14.5%), suspected pancreatic mass (10.4%), chronic
      hyperamylasemia (6.2%), and acute biliary pancreatitis (16.6%). Except for acute
      biliary pancreatitis (significantly more frequent in duplication variants), no
      statistical difference was observed between the groups with anatomical variants
      concerning clinical features.

PMID- 8568332
TI  - No negative feedback regulation between plasma CCK levels and luminal tryptic
      activities in patients with pancreatic insufficiency.
AB  - The study was conducted on five healthy subjects and six patients with calcifying
      pancreatitis (CP) and steatorrhea. Following overnight fasting, one tube each was
      placed in the stomach and the upper of the small intestine, respectively. Through
      the gastric tube, a test meal that included 30 g of fat (total calories, 625
      kcal, 500 mL) was infused over a span of 30 min. Every 30 min (up to 150 min),
      fluid samples in the upper small intestine were collected and chilled, and the
      amylase, trypsin, and lipase levels were determined. In addition, in the case of
      the CP patients, a high-potency pancreatin preparation was infused into the
      stomach together with the test meal. In order to determine the plasma CCK level,
      blood sample were collected before test meal infusion and at 10, 20, 30, 45, 60,
      90, 120, and 150 min subsequent to infusion. The plasma CCK was extracted using a
      Sep-Pak C-18 cartridge and analyzed with radioimmunoassay using an OAL-656
      antibody. The result was converted to the CCK-8 level and expressed in pg/mL. The
      enzyme activities in the upper small intestine of the CP patients after test meal
      administration amounted to 22.8 (amylase), 10.8 (trypsin), and 16.9% (lipase)
      compared with the corresponding figures for the normal subjects. Following
      administration of a high-potency pancreatin in patients with CP, enzyme
      activities in the upper small intestine increased to 132.2 (amylase), 38.7
      (trypsin), and 45.3% (lipase) compared with levels in the normal subjects.
      However, the healthy subjects and the CP patients, both with and without
      treatment with supplementary exogenous enzymes, all exhibited similar profiles in
      the plasma CCK response to stimuli. Based on these findings, we concluded that a
      negative feedback mechanism does not exist between the tryptic activity of the
      upper small intestine and the CCK secretory response in patients with chronic
      pancreatitis.

PMID- 8568333
TI  - Digestive and nutritional consequences of pancreatic resections. The classical vs
      the pylorus-sparing procedure.
AB  - Digestive and nutritional alterations are a common occurrence after pancreatic
      resections. The authors report the results of a multiparametric evaluation
      performed in a group of 26 patients submitted to total or cephalic
      pancreatectomy. Patients were divided into two groups according to the surgical
      procedure; group A (n = 13) included gastroresected patients and group B (n = 13)
      included those submitted to pylorus-sparing pancreatic resection. Subclinical
      digestive and absorptive impairment has been found in 61.5% of group A patients;
      the nutritional status was clinically poor in four cases from the same group.
      Digestive alterations have also been found in 69.2% of group B cases, but
      nutritional status was always satisfactory in the whole group. The more positive
      results obtained with the pylorus-sparing technique encourage wider adoption of
      this procedure.

PMID- 8568334
TI  - Pancreatic involvement in patients with Sjogren's syndrome and primary biliary
      cirrhosis.
AB  - Serum pancreatic enzyme activities, exocrine pancreatic function, and pancreatic
      ductal morphology were evaluated in patients with one or both of Sjogren's
      syndrome and primary biliary cirrhosis. Ten of 20 patients with Sjogren's
      syndrome (50%), 6 of 17 patients with primary biliary cirrhosis (35%), and 4 of
      11 patients with both diseases (36%) had an elevated level of at least one
      pancreatic enzyme, including elastase-1, lipase, and trypsin. Diminished
      excretion of N-benzoyl-L-tyrosyl-para-aminobenzoic acid was observed in 3 of 17
      patients with Sjogren's syndrome (18%), 4 of 16 with primary biliary cirrhosis
      (25%), and none of 7 with both diseases. Endoscopic retrograde pancreatograms
      demonstrated an abnormal pancreatic ductal configuration in 3 of 11 patients with
      Sjogren's syndrome (27%), 2 of 9 with primary biliary cirrhosis (22%), and 3 of 4
      with both diseases (75%). Only minimal changes in branches of the pancreatic duct
      were observed in the pancreatogram. Finally, 9-30% of patients with Sjogren's
      syndrome and/or primary biliary cirrhosis had a mild and intermittent abdominal
      pain. These findings support the concept of a disease complex, "autoimmune
      exocrinopathy," in patients with Sjogren's syndrome, primary biliary cirrhosis,
      and chronic pancreatitis.

PMID- 8568335
TI  - Cholecystokinin (CCK) in the amino acid uptake and enzyme protein secretion by
      the pancreas in humans.
AB  - Activation of type A receptors by CCK or cerulein is known to stimulate
      pancreatic enzyme secretion, but its role in the amino acid (AA) consumption and
      enzyme synthesis remains unclear. In our study, we used loxiglumide, a potent CCK
      A-receptor antagonist, to investigate the role of CCK-A receptors in pancreatic
      consumption of circulating AAs and enzyme secretion. Five healthy male volunteers
      were intubated with double-lumen duodenal tube, and duodenal aspirates were
      collected during 60-min basal periods and then during pancreatic stimulation with
      iv infusion of secretion (80 pmol/kg/h) plus cerulein (50 pmol/kg/h) during three
      consecutive 30-min periods. The same procedure was repeated, but secretin
      cerulein infusion was combined with a constant dose of loxiglumide (20
      mumol/kg/h). The volume and outputs of HCO3-, protein and enzymes (amylase and
      trypsin) in duodenal aspirates and gallbladder volume (by sonography) were
      determined at 30-min intervals. Plasma samples were drawn for total plasma AA
      assay by ninhydrin method to assess the pancreatic uptake of free AAs. Infusion
      of secretin plus cerulein caused a several-fold increase in the volume of
      duodenal aspirate and the outputs of HCO3-, protein, and enzymes. During those
      periods, plasma AA level decreased from initially 2.20 +/- 0.3 mmol/L to 1.09 +/-
      0.3 mmol/L (p < 0.01) and the gallbladder volume from initially 28 +/- 8 mL to 2
      +/- 0.4 mL. This increase in pancreatic secretory outputs was accompanied by
      significant increments in plasma insulin, glucagon, PP, and
      somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8568336
TI  - Administration of a nitric oxide synthase inhibitor does not suppress low-dose
      streptozotocin-induced diabetes in mice.
AB  - Nitric oxide (NO) has been reported as being a key mediator of the autoimmune
      destruction of B-cells in type I diabetes, and studies have described a
      suppression of low-dose streptozotocin-induced (LDS) diabetes in mice after the
      use of NO synthase inhibitors. However, these studies disagree with regard to the
      outcome of hyperglycemia and insulitis after treatment with these L-arginine
      analogs. The present study tries to clarify this topic by administering N-nitro-L
      arginine-methylester (NAME) (15 mg/d/mouse/15 d) after an LDS treatment in 108
      male C57BL6/J mice. Glycemia measured at the end of the NAME treatment did show a
      slight, but significant, reduction when compared to LDS control animals (p <
      0.001), but values returned to diabetic levels 2 wk after withdrawal of NAME.
      Morphological observations demonstrated that the degree of infiltration and islet
      B-cell damage was absolutely not inhibited by NAME. In conclusion, treatment with
      L-arginine analogs is not capable of protecting mice from LDS-induced diabetes.

PMID- 8568338
TI  - Pleomorphic nonfunctioning islet cell tumor of the pancreas.
AB  - A nonfunctioning islet cell tumor of the pancreas in a 68-yr-old female is
      reported. All of the laboratory data, including serum hormones, glucose, and
      tumor markers, were within normal limits. A pancreatoduodenectomy was performed.
      Cut sections of the specimen revealed a cystic mass measuring 6.0 x 4.5 x 3.5 cm.
      Histologically, the tumor consisted of large acidophilic cells with bizarre giant
      nuclei. The tumor cells were positive for chromogranin-A, synaptophysin, neuron
      specific enolase, and S-100 protein. Multifocal proliferation of endocrine cells,
      centroacinar cells and changes in acinar cells were found in the adjacent
      uninvolved pancreatic tissue. Ultrastructural studies of the tumor revealed clear
      nuclei with no zymogen, but immature neurosecretory granules in the cytoplasm of
      the tumor cells. These findings were consistent with those of nonfunctioning
      islet cell tumors, especially of the pleomorphic type. To the best of our
      knowledge, this is the first report on pleomorphic nonfunctioning pancreatic
      islet cell tumors.

PMID- 8568337
TI  - Evidence for early oxidative stress in acute pancreatitis. Clues for correction.
AB  - Pancreatic oxidative stress with depletion of pancreatic glutathione is an early
      feature in all tested models of acute pancreatitis, and sooner or later the
      problem extends to the lung, irrespective of disease severity, whether toward
      spontaneous recovery or death from multisystem organ failure. We, therefore,
      sought evidence of oxidative stress in the human disease by analyzing admission
      blood samples. We found it from high concentrations of oxidatively altered
      linoleic acid in serum and vitamin C in plasma (p < 0.001 vs controls or a group
      of other acute abdominal crises where the proportion of patients with admission
      Apache II scores < or > 8 was similar). These changes were accompanied by
      subnormal levels of ascorbic acid in plasma (p < 0.001); selenium (p < 0.001),
      beta-carotene (p < 0.001), and alpha-tocopherol in serum (p = 0.005 for its molar
      ratio to cholesterol). Paradoxically, the plasma concentration of S
      adenosylmethionine was elevated (p = 0.02), suggesting that this proximate
      bioactive metabolite of the essential amino acid had backtracked because its
      intracellular metabolism down the methionine trans-sulfuration pathway toward
      glutathione synthesis was disrupted. The aberrations transcended putative
      etiological factor, duration of symptoms, or disease severity. We conclude: (1)
      that oxidative stress has pervaded the vascular compartment by the time of
      admission in patients with acute pancreatitis, and, (2) that blood micronutrient
      antioxidant profiles at this stage are consistent not only with compromised
      intracellular capacity to synthesize/refurbish glutathione, but also
      vulnerability of intra- and extracellular lipid targets.

PMID- 8568339
TI  - A case of macrocystic serous cystadenoma of the pancreas.
AB  - A case of macrocystic serous cystadenoma of the pancreas is presented, and
      literature is reviewed. A 35-yr-old woman presented with mild upper abdominal
      pain. Abdominal ultrasonography and an abdominal computed tomography revealed a
      multiloculated and calcified cyst in the body of the pancreas. A T1-weighted
      image, using magnetic resonance imaging, revealed a low-intensity multiloculated,
      pancreatic mass. In contrast, T2-imaging of the tumor showed a high-intensity
      mass. Endoscopic retrograde cholangiopancreatography showed no contact between
      the main pancreatic duct and the tumor. The preoperative diagnosis was a mucinous
      cystic neoplasm. Tumor enucleation was performed. Subsequent microscopic
      examination of this tumor suggested the diagnosis of a macrocystic serous
      cystadenoma of the pancreas.

PMID- 8568340
TI  - Leiomyosarcoma of the pancreas.
AB  - A 45-yr-old female patient was admitted with signs and symptoms of acute
      pancreatitis. She had no history of gallstones, alcohol, or trauma. Her CT scan
      was consistent with a cystic lesion of the pancreas. Because of her presenting
      symptoms and signs, she was initially treated as an acute pancreatitis. Followup
      CT scan showed absolutely no change in the cyst. Surgical consultation was
      requested. A diagnosis of a neoplastic cyst was made, and the patient was taken
      to surgery where a distal pancreatectomy and splenectomy was performed. Pathology
      revealed a leiomyosarcoma of the pancreas. Only 15 other cases of leiomyosarcoma
      of the pancreas have been reported thus far in literature.

PMID- 8568341
TI  - Neuroendoscopic third ventriculostomy: a nursing perspective.

PMID- 8568342
TI  - After the party's over: evaluation of a drinking and driving prevention program.
AB  - This study evaluated a neuroscience nursing community outreach program titled,
      "After the Party's Over," focused on teenage drinking and driving prevention. The
      program consisted of a 20-minute slide presentation with contemporary music and
      narration that depicted graphic pictures of actual patients who sustained severe
      head and spinal cord injuries (SCIs) as a result of motor vehicle accidents
      (MVAs). A convenience sample of 274 high school drivers' education students was
      obtained. A Likert-type scale that measured reported behaviors was administered
      immediately before and after the program and one month after program completion.
      Results indicated a significant change in reported driving behavior of teenagers
      who participated in this program.

PMID- 8568343
TI  - MELAS: a mitochondrial encephalomyopathy syndrome.
AB  - MELAS, a syndrome characterized by Myopathy, Encephalopathy, Lactic Acidosis and
      Stroke-like episodes, is one of a group of diseases known as mitochondrial
      encephalopathies. These genetically-transmitted diseases result in metabolic
      abnormalities associated with mitochondrial dysfunction, which contribute to
      neuronal destruction. Clinical manifestations include dementia, seizures, muscle
      weakness and stroke-like episodes. Accurate diagnosis is difficult to make and
      effective treatment is nonexistent at this time. The focus of care is supportive
      and the nurse's role centers on identification of deficits and maintenance of
      existing function.

PMID- 8568344
TI  - Interrater reliability of the Glasgow Coma Scale.
AB  - The purpose of this study was to test the interrater reliability of the Glasgow
      Coma Scale (GCS) when used in assessing neurologically impaired patients. In
      order to control variables, a videotape was developed of seven patients with
      different neurological impairments. A total of 57 nurses and physicians with
      varying degrees of education and experience used the GCS to score the patient
      responses. These responses were then compared for consensus and against a
      criterion standard. The comparison showed a low disagreement rating and a
      moderate to high agreement rating demonstrating that this tool has good
      interrater reliability (p = 0.000). Nurses may use this tool with confidence as
      one measure of assessment in evaluating neurologically impaired patients.

PMID- 8568345
TI  - A sensitive and semi-quantitative pediatric myoclonus evaluation scale.
AB  - One of the difficulties in evaluating myoclonus in childhood is the lack of a
      standardized scale which addresses the constraints of pediatric scoring. The
      scale needs to be simple and rapid as well as sensitive and semi-quantitative and
      applicable across different ages. We videotaped children and young adults with
      myoclonus of various etiologies, such as progressive myoclonus epilepsy,
      opsoclonus-myoclonus and other acquired etiologies, and scored the videotapes
      using a new scale. Each clinical type of myoclonus (spontaneous, action and
      sensory-evoked myoclonus) was graded separately on a five-point scale for
      severity, intensity and distribution. Data were evaluated as separate scores and
      also combined for a total score. Validity and reliability were tested using a
      judge panel of three blinded, trained observers. Action myoclonus was the
      predominant form of myoclonus in our patients, and was significantly greater than
      spontaneous and sensory-evoked myoclonus in frequency, intensity and
      distribution. Separate statistical analysis performed for progressive myoclonus
      epilepsy and for opsoclonus-myoclonus showed the same pattern. Total scores
      between etiologies of myoclonus for frequency and distribution categories were
      significantly different. Subscores and total scores were highly correlated. We
      found the new scale to be flexible and adaptable for children and there were few
      missing values due to non-applicability of a scale item. It was useful for all
      pediatric age groups. The scale and videotape instructions provide a reliable
      tool for use in pediatric myoclonic disorders.

PMID- 8568346
TI  - Understanding computerized EEG monitoring in the intensive care unit.
AB  - Computerized EEG (CEEG) monitoring has recently been introduced to intensive care
      units (ICU). Unlike the intermittent assessment using coma scales, CEEG
      monitoring provides continuous information about a patients' neurological
      condition. Patient status can be monitored more accurately with CEEG. The use of
      CEEG monitoring has been proposed for those patients who may experience a decline
      in cerebral blood flow related to increased intracranial pressure (ICP) or other
      ischemic events. CEEG is also used in status epilepticus, non-convulsive
      seizures, metabolic disorders, intracerebral tumors and all etiologies of coma.
      The goal of continuous CEEG monitoring is to recognize a decline in a patient's
      condition before physical signs and symptoms are present. The neuroscience nurse
      participates in the assessment of the EEG recording as well as in evaluating
      therapy. This article introduces the neuroscience nurse to the basic terminology,
      rationale for use and clinical application for continuous computerized EEG
      monitoring.

PMID- 8568347
TI  - Hope: implications for neuroscience nursing.
AB  - Hope is a response of patients and families to actual and potential health
      problems. The study of this phenomenon in neuroscience populations is limited.
      Facilitating hope in the health care setting results from an understanding of its
      definition and significance to nursing, multidisciplinary origins and scientific
      investigations. Nursing interventions should include attention to the
      environment, goals, relationships, change and energy.

PMID- 8568348
TI  - Social support: gender differences in multiple sclerosis spousal caregivers.
AB  - The purpose of this study was to investigate gender differences in social support
      of spousal caregivers of persons with multiple sclerosis (MS). The sample
      consisted of 37 male and 28 female caregivers of individuals with MS. It was
      found that female caregivers scored significantly higher than males on the total
      number of resources available, perceived social support and the perceived
      availability of friends and self-help groups. There was a positive relationship
      between caregiver-perceived social support and the ability of the mate to perform
      intimate functions. Caregiver-perceived social support was also found to be
      positively correlated with the caregiver's level of commitment to the spousal
      relationship.

PMID- 8568349
TI  - Client assessment tool: a means to enhance nurse-client-physician collaboration.
AB  - The fast pace of a headache clinic prompted the authors to develop chart forms
      which covered all aspects of history and treatment specific to headache clients.
      The effort proved to be beneficial in promoting better communication between
      caregivers and clients due to ease and thoroughness of documentation. Use of such
      a tool may promote cost effectiveness, better nurse-client-physician
      relationships and ultimately improved client outcomes.

PMID- 8568350
TI  - Practical limits to the uniform determination of death act.
AB  - Death is a transition laden with meaning. Rather than overrule a common lifeworld
      understanding of death with scientific criteria, a process of involvement and
      interpretation might help health-care practitioners understand what death means
      for the family and the patient and possibly allow all to come to some shared
      agreement on appropriate treatment. The UDDA was offered as a way to standardize
      the practice of diagnosing death based on brain-related criteria. While these
      criteria may be essential to recognizing death in certain circumstances, they
      should not be used as the final word on withdrawal of life-support in the absence
      of or in place of an understanding with the patient's family.

PMID- 8568351
TI  - [Studies on the bone metabolisms in either after natural menopause or surgical
      menopause: implications of IGF-IGFBP system for postmenopausal osteoporosis].
AB  - It is well established that accelerated bone loss occurs in association with
      estrogen deprivation as seen following the natural menopause and in premenopausal
      women undergoing surgical oophorectomy (i.e., surgical menopause). We have
      measured serum levels of bone biochemical markers after both natural menopause
      and surgical menopause. Circulating levels of insulin-like growth factor-I (IGF
      I), which is considered to be the local regulator of osteoblast activity and one
      of its binding protein, insulin-like growth factor binding protein-4 (IGFBP-4)
      which binds to IGF-I and suppress its biological activity, were also measured.
      Bone mineral density measured by dual energy X-ray absorptiometry was decreased
      more rapidly after surgical menopause. A concomitantly higher rate of bone
      turnover as assessed by bone biochemical markers was observed after surgical
      menopause, and thus the levels of procollagen type I C-peptide, pyridinoline and
      deoxypyridinoline were increased. The serum levels of IGF-I were significantly
      reduced after natural menopause compared with that after surgical menopause. The
      levels of IGF-I were correlated with bone mineral density after natural menopause
      (r = 0.62, p < 0.001), but no significant correlation was observed between these
      two variables after surgical menopause. The binding activity of IGFBP-4 was
      significantly greater after surgical menopause than after natural menopause. A
      stronger inverse correlation existed between the binding activity of IGFBP-4 and
      bone mineral density after surgical menopause (r = -0.90, p < 0.001) compared to
      that after natural menopause (r = -0.29, p < 0.05). The simplest explanation is
      that whereas the loss of bone depends upon the decreased level of IGF-I after
      natural menopause, after surgical menopause it depends upon the increased level
      of IGFBP-4.

PMID- 8568352
TI  - [A novel method of ovarian stimulation for in vitro fertilization (bromocriptine
      rebound method) increases developmental potential of oocytes and pregnancy rate].
AB  - A novel method of ovarian stimulation for IVF is reported. Endocrine-normal
      ovulatory women with a history of unsuccessful IVF attempts by means of a long
      protocol of a GnRH agonist/hMG regimen (L regimen) were studied. Ovaries were
      stimulated by the three regimens described below. The bromocriptine-rebound (BR)
      regimen consisted of bromocriptine (B) 2.5mg/day administered daily beginning on
      day 4 of the preceding cycle and buserelin acetate administered beginning in
      early high phase. Administration of B was discontinued in the low phase of the
      IVF cycle and daily administration of hMG was begun 7 days later. HCG was
      administered when dominant follicles reached 16-18 mm in diameter. The
      bromocriptine-continuous (BC) regimen was the same as the BR regimen, except that
      B was administered until the administration of hCG. The L regimen was the same as
      the BR regimen, except that no B was administered. The pregnancy rate per oocyte
      retrieval was significantly higher on the BR regimen (56% in 70 cycles) than the
      L regimen (33% in 46 cycles), and lowest on the BC regimen (29% in 7 cycles). The
      rate of fertilization and cleavage per oocyte and the proportion of
      morphologically-good embryos were significantly higher on the BR regimen (59.1%
      and 57.3%, respectively) than the L regimen (46.3% and 48.0%, respectively), and
      lowest on the BC regimen (49.0% and 41.7%, respectively). Serum PRL
      concentrations (ng/ml) at the time hMG was started were 14.9 +/- 1.5, 7.9 +/- 1.7
      and 2.5 +/- 0.7 on the BR, L and BC regimens, respectively. The results of this
      study show that the BR regimen increases the developmental potential of oocytes
      and the pregnancy rate, probably because of increasing serum PRL levels to within
      the normal range.

PMID- 8568353
TI  - [Induction and release of manganese superoxide dismutase caused by tumor necrosis
      factor-alpha from mitochondria in human umbilical vein endothelial cells].
AB  - The effects of tumor necrosis factor-alpha (TNF-alpha) on cultured human
      umbilical vein endothelial cells (EC) and five cancer cell lines, A549, ME180,
      A2780, KURAMOCHI, and Hela, were compared. While A549, A2780, KURAMOCHI, and Hela
      cells were fairly resistant to the cytolytic effects of TNF-alpha, ME180 cells
      were sensitive. EC were also less sensitive to TNF-alpha than ME180 cells as
      judged by the viability of individual cells and by the release of lactate
      dehydrogenase (LDH) into the medium. Manganese superoxide dismutase (Mn-SOD) was
      markedly induced by these cytokines in EC and in A549 cells but not in ME180
      cells. The levels of Mn-SOD in the conditioned medium of EC were dramatically
      increased after stimulation with cytokines, whereas those in ME180 and A549 cells
      were relatively low. The amount of Mn-SOD released appears to be comparable to
      that from cells lysed by other means. Immunoblot analysis of Mn-SOD in the medium
      showed that the molecular mass of the immunoreactive protein was the same as
      mitochondrial Mn-SOD, indicating that no proteolysis had occurred. These data
      suggest that in vivo the TNF-alpha produced by cancer cells may induce Mn-SOD in
      vascular endothelial cells, resulting in release of a relatively large amount of
      this protein into the serum.

PMID- 8568354
TI  - [The relationship between blood flow redistribution in umbilical artery and
      middle cerebral artery and fetal growth in intrauterine growth retardation].
AB  - The aim of this study was to evaluate the usefulness of umbilical artery and
      middle cerebral artery PI and the ratio of these values as predictors of fetal
      growth-retardation and adverse perinatal outcome. In 100 normal fetuses and 105
      intrauterine growth-retarded fetuses Doppler velocity waveforms were recorded
      from the umbilical artery and middle cerebral artery, and we calculated the
      incidence of low birth weight, gestational age at delivery, fetal distress and
      umbilical artery blood gas. The results were as follows: 1. There were moderate
      correlations between umbilical PI and birth weight (r = -0.43, p < 0.0001) and
      between middle cerebral artery PI and birth weight (r = 0.37, p < 0.0001) and a
      close correlation between cerebral-umbilical PI ratio and birth weight (r = 0.71,
      p < 0.0001). 2. There was a significant association between the cerebral
      umbilical PI ratio and the HC/AC ratio (r = -0.46, p < 0.0001). 3. The cerebral
      umbilical PI ratio was the best predictor of birth weight, fetal distress and
      neonatal mortality compared with umbilical artery PI and middle cerebral artery
      PI. In growth retarded fetuses, high umbilical artery PI and low middle cerebral
      artery PI, the so called "brain sparing effect" was demonstrated. The cerebral
      umbilical PI ratio provided a better predictor of IUGR and adverse perinatal
      outcome than umbilical artery PI and middle cerebral artery PI alone.

PMID- 8568355
TI  - [Clinical study on the intracranial arteriovenous malformation associated with
      pregnancy].
AB  - We studied twelve pregnancies in nine patients with arteriovenous malformation
      (AVM) managed at our hospital from January, 1984 to March, 1993. Three of the
      cases were diagnosed as subarachnoidal hemorrhage (SAH) and one as epilepsy
      during pregnancy. The AVM was resected surgically in two ruptured cases during
      pregnancy, and the fetus was delivered vaginally. In the other case of ruptured
      AVM delivery was by elective cesarean section. In the non-ruptured case delivery
      was vaginal. Two of the six patients who took an anticonvulsant developed
      hemolytic anemia, and one baby was born with a cleft lip and palete. We next
      retrospectively investigated 42 women who were followed up for AVM at the
      department of neurosurgery in our hospital from January, 1978 to March, 1995.
      Three pregnancies of a total of 46 pregnancies were complicated by a cerebral
      hemorrhage. The hemorrhage rate during pregnancy for women with unruptured AVM
      was 0.065 +/- 0.036 per person per year. There was no significant difference
      between the hemorrhage rate for pregnant women and that for nonpregnant women of
      childbearing age, and the risk for rupture of AVM was not increased in pregnancy.

PMID- 8568356
TI  - [Prenatal detection of the growth-retarded fetuses with a serious risk of adverse
      perinatal outcome by uterine artery Doppler flow velocimetry: a prospective
      study].
AB  - Our objective was to evaluate the predictive value of uterine artery Doppler flow
      velocimetry with regard to a serious risk of adverse perinatal outcome in growth
      retarded fetuses. A prospective comparative study of pregnancies complicated with
      growth-retarded fetus with normal and abnormal uterine artery blood flow was
      performed. Ninety-three pregnancies were assessed by Doppler flow velocimetry in
      terms of the resistance index at 27-36 weeks. The relative risks (95% Confidence
      Interval) in 52 pregnancies with abnormal uterine artery blood flow compared with
      41 pregnancies with normal uterine artery blood flow were as follows: Premature
      delivery: 2.29 (1.32-3.97), birth weight < 2,000g: 2.94 (1.74-4.97), cesarean
      section for fetal distress: 2.57 (1.30-5.05), admission to NICU: 3.27 (1.60
      6.69). The findings in this study suggest that abnormal uterine artery blood flow
      is associated with a serious risk of adverse perinatal outcome in a pregnancy
      complicated with a growth-retarded fetus. Doppler flow velocimetry of the
      maternal uterine artery is useful for determining the clinical management of a
      pregnancy complicated with a growth-retarded fetus.

PMID- 8568357
TI  - [A case of giant fetal hepatic hemangioma].

PMID- 8568358
TI  - [Recurrent inversion of the puerperal uterus managed with the Ocejo operation].

PMID- 8568359
TI  - [A case of trisomy 19 pseudomosaicism--originated an extra fetal organ].

PMID- 8568360
TI  - [Antenatal diagnosis of acardius amorphous].

PMID- 8568361
TI  - [A case of primary transitional cell carcinoma of the Bartholin gland with human
      papillomavirus type 18 infection].

PMID- 8568362
TI  - [Retrospective analysis of cytology in a case with early invasive cervical
      adenocarcinoma].

PMID- 8568363
TI  - [A case of malignant ovarian granulosa cell tumor with poor prognosis].

PMID- 8568364
TI  - [Total laparoscopic hysterectomy with abdominal wall-lift method].

PMID- 8568365
TI  - [Electrophysiological and MRI study on poor outcome after surgery for cervical
      myelopathy].
AB  - Occasionally, the outcome from laminoplasty for cervical spondylosis is
      disappointing despite an adequate operation. Before surgery, it is difficult to
      diagnose the pathological extent of the involvement of the spinal cord. The
      purpose of this study is to determine the efficacy of magnetic resonance imaging
      (MRI) and of the motor evoked potentials (MEPs) for the indication of the surgery
      and prognosis. Retrospectively, we investigated the MEPs and the MRI image of 31
      patients in surgery for cervical myelopathy, involving 21 cases with cervical
      spondylosis and 10 cases with ossification of the posterior longitudinal
      ligamentum, and compared the findings from those with a poor outcome (n = 31)
      with the findings from those with a good outcome (n = 32). The MEPs from the
      thenar muscle and the tibialis anterior were evoked by transcranial magnetic
      brain stimulation. In the poor-outcome patients, the spinal canal was narrow and
      lumbar spinal canal stenosis was seen in 5 cases which required lumbar
      laminectomy. Before operation, the MEPs from the thenar muscle could not be
      evoked in 5 cases while there was a remarkably prolonged central motor conduction
      time in the other 26 cases. MRI revealed the deformed spinal cord in the involved
      area, and the signal intensity of the involved spinal cord in the T2 weighted
      image was remarkable high. The signal intensity ratio was significantly higher in
      the poor-outcome patients than in the good-outcome patients. This study suggested
      that a high signal intensity in the T2 weighted image and a prolonged conduction
      time or absence of MEPs largely corresponded to the clinical and other
      investigative features of myelopathy responsible for a poor outcome.

PMID- 8568366
TI  - [Histological, magnetic resonance imaging, and discographic findings on cervical
      disc degeneration in cadaver spines: a comparative study].
AB  - A total of 210 cervical intervertebral discs were taken at autopsy from 36
      cadavers, and underwent both magnetic resonance imaging (MRI) and discography to
      compare their diagnostic efficacies for investigating degenerative changes in the
      cervical spine. The age of the subjects had ranged from 43 to 92 years with an
      average of 68.1 years. Following the autopsy, MRI and discography were performed
      on the excised cervical spinal column, and the specimen was then prepared for
      histological examination. The findings were compared with those of the lumbar
      spine that had previously been reported by Yasuma et al. on 1238 lumbar discs
      from 197 cadavers ranging in age from 11 to 92 years. The results were as
      follows: 1) Low intensity in the T2-weighted MRI was well correlated with
      histological degeneration in the cervical disc disc. 2) The rate of appearance of
      the posterior protrusion of the cervical disc on the MRI was in accordance with
      the degree of histological disc degeneration, but it did not always correspond
      with histological posterior protrusion. There was a remarkably high incidence for
      false-positive posterior protrusion on the MRI, which should be kept in mind on
      reading the MRI. 3) In the comparison of the MRI with the discography, a certain
      positive correlation was found as for disc degeneration, but not in complete
      accordance. 4) There was a considerable difference in the patterns of
      degeneration and in posterior protrusion of the discs between the cervical spine
      and the lumbar spine. The posterior protrusion in the cervical disc was more
      likely related to horizontal fissure and hyalinization of the posterior annulus,
      while posterior protrusion in the lumbar disc was often related to reversed
      orientation of the bundles and myxomatous degeneration of the posterior annulus.
      This difference was attributed to the difference in the mechanical properties of
      the cervical and lumbar spines.

PMID- 8568367
TI  - [Biomechanical study on the optimal running route for anterior cruciate ligament
      reconstruction].
AB  - The purpose of this study was to determine the isometric points for anterior
      cruciate ligament (ACL) reconstruction and to investigate notch impingement with
      isometric reconstruction. The length pattern of ACL was assessed by three
      dimensional bi-plane X-ray photogrammetry for determining the isometric point for
      ACL reconstruction. The isometric points were studied in six fresh cadaveric
      knees with no injury in any ligament. Five femoral and four tibial attachment
      sites were selected for intra-articular reconstruction. In each knee, 20
      different combinations were studied. For extra-articular reconstruction, three
      femoral and three tibial sites were selected. In these knees, nine different
      combinations were studied. One isometric point for intra-articular ACL
      reconstruction was a combination of the 5-mm superior posterior point from the
      femoral attachment of the ACL and the center point of the tibial attachment. The
      other was a combination of the anterior-proximal edge of the femoral attachment
      and anterior edge of the tibial attachment. There were no isometric points for
      extra-articular ACL reconstruction. To investigate notch impingement, eight
      cadaveric knees were studied. One femoral and three tibial attachment sites were
      selected. For the reconstructed ligaments, 8-mm and 10-mm cables were used. In
      each cadaveric knee, six different conditions were studied. When the tibial hole
      was positioned in the center of the attachment of ACL with an 8-mm graft, then
      notch impingement did not occur. When the tibial drill holes were positioned in a
      more anterior position, then notch impingement occurred in all the cadaveric
      knees in which an 8-mm graft was used. With the 10-mm grafts, notch impingement
      occurred in all three bony tunnel conditions. In these conditions, notch
      impingement occurred widely from the medial side of the roof to the wall of the
      lateral femoral condyle. Thus, if the graft diameter is greater than 8 mm,
      adequate notch plasty must be performed.

PMID- 8568368
TI  - [Changes in the acetabular roof produced by Chiari pelvic osteotomy].
AB  - In order to clarify the changes seen in the new acetabular roof produced by
      Chiari pelvic osteotomy, we performed histological investigations post
      operatively, as well as arthrography and arthroscopy before and after the
      operation. Plain X-rays showed an osseous step between the original surface and
      the new acetabular roof. Arthrography demonstrated no step between the original
      acetabular cartilage and the surface of the newly formed acetabular roof. At
      arthroscopy, the surface of the new acetabular roof could be seen to be covered
      by a soft white tissue. Histological specimens were taken from the new acetabular
      roof. Examination revealed that the superficial layer consisted of some oval
      shaped cells with an extracellular matrix slightly stained by safranin O, but not
      by anti-human type II collagen antibodies. In the deepest layer, there was
      cartilage tissue consisting of cartilage-like cells and an extracellular matrix
      which was stained by safranin O and by anti-type II collagen antibodies. However,
      the staining intensity of this cartilage tissue was less than that of hyaline
      cartilage, and the direction of collagen fibers could be clearly seen. These
      results suggested that the tissue covering the new acetabular roof had no ability
      to change into hyaline cartilage, despite the superficial layer creating a smooth
      surface. It was suggested that the bony modification of the new acetabular roof
      resulted from enchondral ossification of the deepest layer.

PMID- 8568369
TI  - [Strain distribution in the L1 vertebra under axial load and load transmitting
      behavior between the vertebral body and posterior elements].
AB  - This study investigated the stress distribution in the L1 vertebra under a
      vertical axial load. Five normal spinal units (T12-L2) were obtained from
      embalmed human cadavers, to measure the surface strain in the L1 vertebra. Stress
      screening using a brittle-coat was prepared beforehand, then fourteen sites on
      the lateral half of the surface on the L1 vertebra were carefully chosen to
      install rosette strain gauges. A vertical axial load was applied up to 1471 N in
      two degrees of flexion, in the neutral position, and in two degrees of extension
      of the intact spine, and in the neutral facetectomized spine. The strain at each
      site was measured with strain gauges, then the tensile, compressive and shear
      strain values were calculated. Cracks in the brittle-coat showed the strain
      concentration in the base of the pedicles and rims on the superior vertebral
      body. Analysis of the data by strain gauge showed that the amount of strain at
      the rims on the superior vertebral body was greater than that at the inferior
      rims in the three positions of the intact spines, with a statistical
      significance. These strains led to a burst in the superior vertebral body rims.
      As for the posterior elements, the inner surface of the laminas received a
      tensile strain only, while the principal strain on the outer surface of the
      laminas was a compressive strain, in the directions parallel to the laminas.
      These strains led to a transformation in the posterior elements, leading to
      widening in the interpedicular distance and a fracture in the inner surface of
      the lamina. These results showed the first lumbar vertebra was easily
      mechanically injured by a Denis type B burst fracture. Also this study
      demonstrated that the pedicles were the pathway for load transmission.

PMID- 8568370
TI  - [Morphological analysis of the proximal femur by computed tomography in Japanese
      subjects].
AB  - In order to evaluate the morphological features of the proximal femur in the
      Japanese, 100 femora of normal Japanese subjects (normal group) and 60 femora of
      43 Japanese patients with secondary osteoarthrosis of the hip (OA group) were
      analyzed using CT images. The scans for the dried bones (normal group) were done
      at a setting of 80 kV and 20 mA, for 2 sec duration. The scans were reconstructed
      using the soft tissue algorithm built into the GE-9800 scanner. The patient scans
      (OA group) were done at 120 kV and 170 mA also for 2 sec duration, and
      reconstructed using the same bone algorithm. The results were as follows: 1)
      Thinning of the femoral cortex occurred in normal females over 60 years of age.
      2) The canal flare index at the proximal part of the femoral diaphysis was
      negatively correlated with the canal diameter at the isthmus. The index at the
      upper part was greater than that at the lower part. The two groups showed no
      statistical difference in this index. 3) In the metaphysis, the canal flare index
      at the anterior portion was twice that at the posterior portion. In absolute
      terms, the OA group had a reduced flare or curve along the medial portion. 4) In
      cross-section, the canal shape of the diaphysis was more elliptical in the OA
      group than in the normal group. The longitudinal axis of the canal was directed
      more sagittally in the OA group than in the normal group.

PMID- 8568371
TI  - [Analysis of deposits in calcific periarthritis].
AB  - Analysis was conducted on calcific deposits from 5 patients with calcific
      periarthritis. These calcific deposits were dried, immersed in hydrazine, or
      heated to 1000 degrees C for 1 hour, to prepare 3 kinds of samples. The samples
      were classified as dried samples, hydrazine-deproteinated samples, or as heated
      samples. All samples were analyzed by X-ray diffraction (XRD). Fourier transform
      infrared spectroscopy (FTIR), Raman spectroscopy (Raman), and by electron probe
      microanalysis (EPMA). Although the XRD patterns of the dried samples and of the
      deproteinated samples were similar to that of hydroxyapatite (HAp), it was still
      unclear whether or not the calcific deposits were HAp. FTIR then revealed that
      the dried samples contained carbonate. Raman showed that the dried samples and
      the deproteinated samples do not have an OH-group. The dried samples were then
      heated to 1000 degrees C for one hour and analyzed by all 4 methods. The heated
      samples were found to be HAp. From these results, the calcific deposits from the
      5 patients with calcific periarthritis were found to be carbonate apatite: Ca10-x
      y/2 (PO4)6-x (CO3) x (OH) 2-y (CO3)y/2.nH2O.

PMID- 8568372
TI  - [Automatic determination for bone morphometry using a computed image analyzer].
AB  - An image analyzer which combines a digitizer and a computer is widely employed in
      bone histomorphometrical evaluation. With this method, however, all regions of
      determination are traced manually so that considerable time is consumed when many
      preparations are measured. To resolve this problem, we have developed an
      automatic program for rapid and quantitative measurement of many bone
      histomorphometrical parameters using a computed color image analyzer. The bone
      volume (BV), tissue volume (TV), osteoid surface (OS), and the bone surface (BS)
      of rat tibia metaphysis were measured by this automatic method, and by the manual
      method using an image analyzer. The correlation coefficient between both methods
      in measuring BV/TV was 0.98 and in measuring OS/BS was 0.96. The reproducibility
      and accuracy of both methods for these parameters were similar. The time required
      for the automatic method was much shorter than that for the manual method.
      Various parameters of the tibial metaphysis, lumbar vertebral body, and femoral
      mid-diaphysis in ovariectomized rat (Fischer) measured by this method were in
      good agreement with values reported previously.

PMID- 8568373
TI  - [The effect of sodium fluoride on bone mineral density and bone strength in
      ovariectomized rats].
AB  - An experimental study was performed to evaluate the effects of sodium fluoride
      (NaF) on bone mineral density (BMD) and bone strength in rat. Sixty-nine female
      Wistar rats aged 12 months were used. Ovariectomy was carried out in 59 rats, and
      3 of these were sacrificed to confirm osteopenia at 6 months after the
      ovariectomy. Twenty-eight of the remaining 56 rats were given NaF. Half of this
      NaF Group was given high-Ca feed and the other half was given normal feed. And
      one half of the High-Ca Group and one half of the Normal Feed Group were given
      vit. D. The other 28 rats in the Non-NaF Group were given high-Ca and vit. D as
      in the NaF Group. Accordingly, eight groups were created, each with seven rats.
      All were treated for 9 weeks. An additional 10 rats were used for control. At 6
      months after a sham operation, three of these controls were sacrificed to confirm
      non-osteopenia. The remaining seven controls were given normal feed for 9 weeks.
      Therefore, there was total of 9 groups (69 rats). At eight months after the
      surgery (ovariectomy or the sham procedure), both femurs were removed from each
      rat. The BMD was measured over the entire femur by the DXA method. Bone strength
      was measured by three-point bending, compression and penetration tests. BMD was
      found to be higher in the NaF Group than in the Non-NaF Group or Control Group,
      and was highest in the NaF-high-Ca feed Group. In the bone strength test, the NaF
      Group scored higher than the Non-NaF Group. In the three-point bending and
      penetration tests, the NaF-high-Ca feed Group was highest. A linear correlation
      was found between the BMD and bone strength. There was no effect produced by the
      administration of the vit. D on the BMD or bone strength. In conclusion, the
      experimental administration of NaF, and of high-Ca feed, increased BMD and bone
      strength.

PMID- 8568374
TI  - [Effects of bisphosphonates on vitamin A-induced bone resorption in
      thyroparathyroidectomized rat].
AB  - A bone resorption model in which osteoclasts were selectively activated was made
      by administering vitamin A--a bone resorption agent--to juvenile
      thyroparathyroidectomized rat. Inhibition of bone resorption by YM-175--a third
      generation bisphosphonate--was studied using this model based on bone
      histomorphometry of the proximal part of the tibia and on biochemical data. Six
      week-old male SD rats were thyroparathyroidectomized (TPTX). On the 11th day
      following TPTX they were treated with vitamin A (etretinate). In the calcitonin
      group, salmon calcitonin or its vehicle was added, and in the bisphosphonate
      group, YM-175 or its vehicle was added. They were sacrificed on the 21st day
      following TPTX. Calcitonin was used to confirm its inhibitory activity of bone
      resorption in this model. Cancellous bone in the epiphysis was subjected to
      histomorphometry using tetracycline labeling or TRAP staining, and the number of
      primary trabeculae at the metaphysis was counted to evaluate bone resorption
      activity. Serum calcium, phosphorus, urinary calcium, phosphorus, pyridinoline
      and deoxypyridinoline were measured for biochemical analysis. YM-175 did not
      change any bone formation parameters in the histomorphometry of the epiphysis,
      while it significantly decreased resorption parameters both histomorphometrically
      and biochemically. Primary trabeculae at the metaphysis were found to be longer
      and denser after administration of YM-175. The effect of YM-175 as a bone
      resorption inhibitor was observed even in a short duration experiment. There was
      no damage to mineralization, and no inhibiting effect was observed on bone
      formation. Similar results were observed by calcitonin. YM-175 was concluded to
      be an inhibitor of bone resorption caused by vitamin A administration.

PMID- 8568375
TI  - [Emergency drug therapy of bronchial asthma].

PMID- 8568376
TI  - [Emergency drug therapy of pulmonary thromboembolism].

PMID- 8568377
TI  - [Emergency drug therapy of arrhythmia].

PMID- 8568378
TI  - [Emergency drug therapy of acute heart failure and cardiogenic shock].

PMID- 8568379
TI  - [Emergency drug therapy of non-specific inflammatory bowel diseases--progress on
      diagnosis and therapy].

PMID- 8568380
TI  - [Emergency drug therapy of fulminant hepatitis].

PMID- 8568381
TI  - [Emergency drug therapy of acute pancreatitis].

PMID- 8568382
TI  - [Emergency drug therapy of cerebrovascular disease].

PMID- 8568383
TI  - [Emergency drug therapy of meningoencephalitis].

PMID- 8568384
TI  - [Emergency drug therapy of diabetic coma].

PMID- 8568386
TI  - [Emergency therapy of acute kidney failure and water-electrolyte imbalance].

PMID- 8568385
TI  - [Emergency drug therapy of thyroid disease].

PMID- 8568387
TI  - [Emergency therapy of disseminated intravascular coagulation].

PMID- 8568388
TI  - [Emergency therapy of collagen diseases and their complications].

PMID- 8568390
TI  - [Emergency drug therapy of internal diseases (discussion)].

PMID- 8568389
TI  - [Emergency therapy of sepsis].

PMID- 8568391
TI  - [A case of 3243 point mutation of mitochondrial gene with diabetes mellitus
      treated with large dose of coenzyme Q].

PMID- 8568392
TI  - [A case of thyroid crisis diagnosed at the time of consciousness disorder].

PMID- 8568393
TI  - [Interesting case of pulmonary alveolar proteinosis].

PMID- 8568394
TI  - [A case of ileo-vesical fistula with recurrent metabolic encephalopathy].

PMID- 8568395
TI  - [A case of ulcerative colitis with sulphasalazine induced megaloblastic anemia].

PMID- 8568396
TI  - [Recent food poisoning and molecular biology].

PMID- 8568397
TI  - [Hormone signal transduction and G protein].

PMID- 8568398
TI  - [Significance of clonality study in hematological diseases].

PMID- 8568399
TI  - [Contraindication of ATP related drugs for therapy of gout and uric acidemia].

PMID- 8568401
TI  - Clinical results and manometric studies after rectal flap advancement for infra
      levator trans-sphincteric fistula-in-ano.
AB  - Eleven patients with infra-levator trans-sphincteric fistula-in-ano underwent
      fistula excision with rectal flap advancement. The clinical results were assessed
      by interview and the physiological function determined by ano-rectal manometry.
      Nine patients underwent paired studies before and 5 (range 2 to 6) months after
      operation. Median maximum resting anal pressure was 84 (48-135) cm water before
      operation and 76 (29-139) cm water after operation (P = N.S.). Median maximum
      squeeze pressure was 112 (64-290) cm water before operation and 88 (44-316) cm
      water after operation (P = N.S.). The median sphincter length was preserved after
      operation. There was one clinical failure following the development of an abscess
      under the flap. All patients are continent and there have been no recurrences. We
      conclude that rectal flap advancement is an acceptable way to cure more complex
      fistula-in-ano. Good functional results are achieved by maintaining anal
      sphincter function together with preservation of the integrity of the anal
      margin.

PMID- 8568400
TI  - Management of rectourethral fistulas in Crohn's disease.
AB  - We report the thirteenth case of a recto-urethral fistula in Crohn's disease. The
      patient, a 37-year-old white male, had a 20-year history of intestinal Crohn's
      disease and had undergone numerous bowel resections. His symptoms were fecaluria,
      urorrhea and passing of urine from an orifice just outside the base of the
      scrotum. He had urinary infection and severe ileocolitis. He underwent a
      diagnostic evaluation (cystourethroscopy, proctoscopy, retrograde pyelography,
      intravenous urography, voiding cystourethrography) that revealed a fistula
      comprising the membranous urethra, the rectum, the perineum and the scrotum. He
      was treated with Metronidazole (20 mg/kg/day/12 mo). At 1 year no signs of
      intestinal disease and urinary sepsis were noted. The external orifice and the
      perineal fistulous network were closed, and the drainage from the rectum and the
      urethra had improved. No side effects limited use of the drug. No relapse was
      observed in the 3 months, after the therapy was discontinued. We present a review
      of the literature on the management of rectourethral fistulas in Crohn's disease.
      Surgeons have used successfully several approaches in the repair of this lesion,
      but no single procedure has proved optimal or even universally applicable. We
      emphasize, as the literature suggests, that the management must be
      individualized. Medical therapy with metronidazole has an important role in a
      patient with rectourethral fistula and concomitant proctitis, ileocolitis,
      urinary sepsis and multiple previous surgical procedures.

PMID- 8568402
TI  - Influence of proximal end diverting colostomy on the healing of left-sided
      colonic anastomosis: an experimental study in rats.
AB  - The purpose of this study was to evaluate the healing of an experimental left
      sided colonic anastomosis in rats protected by an end diverting proimal
      colostomy. The anastomoses were studied by radiological and biochemical
      examination and breaking strength was estimated. The results were compared with a
      non-operated group and with a group of rats having a non-defunctional anastomosis
      constructed in the same manner. In animals with an end diverting colostomy,
      anastomotic protein levels and enzymic activity were lower than in those with a
      colostomy, and the development of anastomotic strength was delayed compared with
      those not defunctioned.

PMID- 8568403
TI  - Closure of rectal stump after colectomy for acute colitis.
AB  - In a retrospective study complications, mortality and morbidity following acute
      colectomy for severe colitis with intra-abdominal closure of the rectal stump
      were reviewed in 147 consecutive patients (71 women and 76 men, median age of 40
      years, range 18-95 years). Five patients (3%) died within 30 days
      postoperatively; none of the deaths were related to the rectal stump. Three
      patients (2%) had a pelvic abscess due to leakage of the rectal closure, all were
      treated successfully with percutaneous drainage, guided by ultrasonography. No
      difficulties in locating the rectal stump or performing intended subsequent
      surgery were reported. The overall complications and mortality rate in this study
      are low and comparable to the best results reported from centers using the mucous
      fistula. Closure of the rectal stump is a safe procedure, and has the advantage
      of not leaving the patient with a second stoma.

PMID- 8568404
TI  - Prevalence of sexual abuse among patients with functional disorders of the lower
      gastrointestinal tract.
AB  - To evaluate the links between gastrointestinal disorders and sexual abuse, we
      asked 344 patients consulting in a specialized tertiary care university hospital
      or a gastroenterologist in private practice, if they had been sexually abused.
      Forty per cent of patients suffering from lower functional digestive disorder
      gave a history of having been victims of sexual abuse in contrast to only 10% of
      patients with organic diseases (P < 0.0003). The prevalence was similar in
      private practice and in the university hospital. Abused patients were more likely
      to complain of constipation (P < 0.03) and diarrhoea (P < 0.04). Anismus was more
      frequent in patients who had been sexually abused (P < 0.02). The prevalence of
      abuse was four times greater in patients with lower than with upper functional
      motor disorders of the gastrointestinal tract (P < 0.002). This study confirms
      the large prevalence of a past history of sexual abuse among patients consulting
      for gastrointestinal tract functional disorder, and this whatever the kind of
      recruitment may be. It shows the association to be much stronger in patients who
      have a lower rather than an upper gastrointestinal dysfunction, the major
      complaint of abused patients being constipation and diarrhoea.

PMID- 8568405
TI  - Treatment of recurrent high anal fistula by total excision and primary sphincter
      reconstruction.
AB  - Fourteen patients with recurrent high anal fistula were treated by total excision
      of the fistulous tract with primary sphincter reconstruction. Nine patients with
      sepsis had seton drainage for one to three months before the operation. The
      surgical approach was the transsphincteric technique described by Mason. No
      covering stoma was used routinely, but three patients referred with a colostomy
      had the stoma closed 3 to 5 months later. After a follow-up from 1 to 4 years two
      patients had recurrence, which in one necessitated a diverting ileostomy. Three
      patients, one with recurrence and two without, suffered from minor anal
      incontinence. It is concluded that total excision with primary sphincter
      reconstruction is a treatment modality which should be considered for recurrent
      high anal fistula, especially in patients where closure by an advancement flap is
      not possible.

PMID- 8568406
TI  - Technetium-labelled red blood cell scintigraphy: is it useful in acute lower
      gastrointestinal bleeding?
AB  - Radionuclide scintigraphy is commonly utilized as a screening examination before
      performing more invasive procedures in the work-up of patients with lower
      gastrointestinal (GI) bleeding. We reviewed our institutional experience with
      technetium-labelled red blood cell scintigraphy (TRCS) in detecting and
      localising acute lower GI bleeding. The study group included 72 patients who had
      80 red cells scans over a five year period. Thirty-eight scans were positive
      (47.5%), and 42 were negative (52.5%). Sites of lower GI bleeding were confirmed
      by endoscopy, arteriography, surgery and/or pathology in 22 of the 38 positive
      scans. There were four false-negative scans (9.5%). The overall sensitivity and
      specificity of TRCS in detecting lower GI bleeding was 84.6% (22/26) and 70.4%
      (38/54), respectively. The accuracy of localization of bleeding sites in the
      patients with confirmed positive scans was 72.7% (16/22). Thirty mesenteric
      arteriograms were performed on patients in this series. Eleven arteriograms were
      performed after negative TRCS; one was positive. Technetium-labelled red blood
      cell scintigraphy appears to be a useful screening examination for patients with
      lower GI bleeding who are hemodynamically stable. This may avoid the potential
      morbidity of arteriography in patients who are not actively bleeding.

PMID- 8568407
TI  - A peroperative comparison of Western and Oriental colonic anatomy and mesenteric
      attachments.
AB  - It has been suggested that the Oriental colon is easier to colonoscope than its
      Western counterpart. The aim of this study was to investigate possible
      differences in colonic anatomy between Western and Oriental patients that might
      explain this observation. Measurements of colonic length and mesenteric
      attachments were taken according to a set protocol from 115 Western (Caucasian)
      and 114 Oriental patients at laparotomy. Sigmoid adhesions were found more
      frequently in Western (17%) compared to Oriental (8%) patients, P = 0.047. A
      descending mesocolon of > or = 10 cm occurred in 10 (8%) Western patients but
      only 1 (0.9%) Oriental patient, P = 0.01. The splenic flexure was more frequently
      mobile in Western patients (20%) compared to Oriental (9%) patients, P = 0.016.
      In 29% - of Western patients the mid-transverse colon reached the symphysis
      pubis, or lower when pulled downwards in contrast to 10% of Oriental patients, P
      < 0.001. There was no significant difference in total colonic length comparing
      Western (median = 114 cm, range 68-159 cm) to Oriental (median = 111 cm, range 78
      161 cm) patients. Western patients have a higher incidence of sigmoid colon
      adhesions and increased colonic mobility when compared to Orientals. These
      findings support the observation that colonoscopy is a more difficult procedure
      in Western patients.

PMID- 8568408
TI  - Colectomy for acute colitis: is it safe to close the rectal stump?
AB  - We report 62 operations for acute colonic inflammatory bowel disease in which the
      rectal stump was closed. Operative findings were of severe colitis in 46, toxic
      megacolon in 8 and faecal peritonitis in 8 patients. Histology showed ulcerative
      colitis in 48, Crohn's disease in 9 and indeterminate colitis in 5 patients.
      Clinical evidence of stump leakage occurred in only one of 53 patients with a
      long rectal stump in contrast to 3 of 9 patients who had a short rectal stump.
      Leaving a very short stump also led to difficulty at subsequent proctectomy in 3
      patients and at restorative proctocolectomy in 1 patient. This suggests that
      careful closure of the rectum above the peritoneal reflection can be a safe means
      of dealing with the rectal stump after total colectomy and ileostomy for acute
      colitis.

PMID- 8568410
TI  - The "guardians of the anus" and their practice.

PMID- 8568409
TI  - Squamous cell carcinoma complicating perianal hidradenitis suppurativa.
AB  - Hidradenitis suppurativa or Verneuil's disease is usually a chronic, recurrent,
      suppurative and cicatricial disorder. It most often affects the skin of the
      axillae, groins and perineum, and less commonly the buttocks and upper thighs. A
      squamous cell carcinoma located in the hidradenitis-affected area is a rare
      complication. We present a review of the twenty-six published cases adding one of
      our own.

PMID- 8568411
TI  - Minimally raised end colostomy.
AB  - The traditional maturation of the mucocutaneous junction of an end colostomy
      often leads to a stoma with no significant projection above the skin. We describe
      a simple method which allows a small spout to be easily created. This technique
      has been used in 30 patients and is believed to diminish leakage. A raised stoma
      is easier for the patient to see and Stoma care nurses prefer them.

PMID- 8568412
TI  - Stapled ileal pouch-anal anastomosis with resection of the anal transition zone.

PMID- 8568413
TI  - Recurrence and soiling after surgery for anal fistulae.

PMID- 8568414
TI  - New technique for creation of stapled ileal J-pouch.

PMID- 8568415
TI  - Living wills, durable powers of attorney for health care, and HIV infection. The
      need for statutory reform.

PMID- 8568416
TI  - Physician-assisted suicide and euthanasia in the United States. Legal and ethical
      observations.

PMID- 8568417
TI  - Privacy and autonomy in the physician-patient relationship. Independent
      contracting under Medicare and implications for expansion into managed care.

PMID- 8568418
TI  - 1994 Le Tourneau Award. An insurer's right to settle versus its duty to defend
      nonmeritorious medical malpractice claims.

PMID- 8568419
TI  - A paroxysmal insanity plea in an 1865 murder trial.

PMID- 8568420
TI  - Fetal viability as a threshold to personhood. A legal analysis.

PMID- 8568421
TI  - The effects of health histories on stochastic process models of aging and
      mortality.
AB  - A model of human health history and aging, based on a multivariate stochastic
      process with both continuous diffusion and discrete jump components, is
      presented. Discrete changes generate non-Gaussian diffusion with time varying
      continuous state distributions. An approach to calculating transition rates in
      dynamically heterogeneous populations, which generalizes the conditional
      averaging of hazard rates done in "fixed frailty" population models, is presented
      to describe health processes with multiple jumps. Conditional semi-invariants are
      used to approximate the conditional p.d.f. of the unobserved health history
      components. This is useful in analyzing the age dependence of mortality and
      health changes at advanced age (e.g., 95+) where homeostatic controls weaken, and
      physiological dynamics and survival manifest nonlinear behavior.

PMID- 8568422
TI  - A mechanism for early branching in lung morphogenesis.
AB  - The lung is a highly branched fluid-filled structure, that develops by repeated
      dichotomous branching of a single bud off the foregut, of epithelium invaginating
      into mesenchyme. Incorporating the known stress response of developing lung
      tissues, we model the developing embryonic lung in fluid mechanical terms. We
      suggest that the repeated branching of the early embryonic lung can be understood
      as the natural physical consequence of the interactions of two or more plastic
      substances with surface tension between them. The model makes qualitative and
      quantitative predictions, as well as suggesting an explanation for such observed
      phenomena as the asymmetric second branching of the embryonic bronchi.

PMID- 8568423
TI  - Perturbation analysis of a two-locus model with directional selection and
      recombination.
AB  - A population genetic two-locus model with additive, directional selection and
      recombination is considered. It is assumed that recombination is weaker than
      selection; i.e., the recombination parameter r is smaller than the selection
      coefficients. This assumption is appropriate for describing the effects of two
      locus selection at the molecular level. The model is formulated in terms of
      ordinary differential equations (ODEs) for the gamete frequencies x = (x1, x2,
      x3, x4), defined on the simplex S4. The ODEs are analyzed using first a regular
      perturbation technique. However, this approach yields satisfactory results only
      if r is very small relative to the selection coefficients and if the initial
      values x(0) are in the interior part of S4. To cope with this problem, a novel
      two-scale perturbation method is proposed which rests on the theory of averaging
      of vectorfields. It is demonstrated that the zeroth-order solution of this two
      scale approach approximates the numerical solution of the model well, even if
      recombination rate is on the order of the selection coefficients.

PMID- 8568424
TI  - A randomized controlled trial of the effect of spinal manipulation in the
      treatment of cervicogenic headache.
AB  - PURPOSE: To determine whether the isolated intervention of high-velocity, low
      amplitude spinal manipulation in the cervical spine has any effect on
      cervicogenic headache. DESIGN: Randomized controlled trial with a blind observer.
      SETTING: Ambulatory outpatient facility in an independent NHS-funded chiropractic
      research institution. PARTICIPANTS: Thirty-nine subjects suffering from frequent
      headaches who fulfilled the IHS criteria for cervicogenic headache (excluding
      radiological criteria). These subjects were recruited from among some 400
      headache sufferers who responded to newspaper advertisements. INTERVENTION: Half
      of the group received high-velocity, low-amplitude cervical manipulation twice/wk
      for 3 wk. The other half received low-level laser in the upper cervical region
      and deep friction massage (including trigger points) in the lower cervical/upper
      thoracic region, also twice/wk for 3 wk. MAIN OUTCOME MEASURE: The change from
      week 2 to week 6 in analgesics use per day, headache intensity per episode and
      number of headache hr per day. RESULTS: Despite a significant reduction in the
      manipulation group on all three outcome measures, differences between the two
      treatment groups failed to reach statistical significance. CONCLUSION: The
      results suggest a possible effect of manipulation on cervicogenic headache, but
      because of methodological problems, such an effect could not be unequivocally
      demonstrated.

PMID- 8568425
TI  - Direction of manual force applied during assessment of stiffness in the
      lumbosacral spine.
AB  - OBJECTIVE: To measure the angle of applied manual force during assessment of
      posteroanterior stiffness in the lumbosacral spine. DESIGN: Ten physiotherapists
      with bachelor's degrees in physiotherapy and postgraduate qualifications in
      manipulative physiotherapy assessed stiffness at 6 lumbosacral vertebral levels
      in a controlled order. Two pain free subjects acted as patients. SETTING: A
      university biomechanics laboratory. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      Applied force vector angles in the sagittal plane. RESULTS: The physiotherapists
      all varied the direction of the force they applied so that it was directed
      slightly toward the feet at the lower vertebral levels and more toward the head
      as they moved up the spine. There was a significant difference between the
      direction of the applied force vector angles at each vertebral level (p < .0001).
      The direction of force used was also significantly different for the two patients
      (p = .0067). The forces used by the physiotherapists were applied in directions
      more vertical than if forces had been applied in directions perpendicular to the
      surface curves of the two patients. CONCLUSION: The direction of the force
      applied by the physiotherapists in this study when assessing posteroanterior
      stiffness varied significantly between vertebral levels and seemed to take into
      account the individual shape of the lumbosacral curve of each patient.

PMID- 8568426
TI  - Comparison of leg length inequality measurement methods as estimators of the
      femur head height difference on standing X-ray.
AB  - OBJECTIVE: To assess the validity and reliability of prone and supine
      measurements of leg length inequality and to determine the potential use of
      measurements at the iliac crests and patient demographics as predictors to
      estimate standing leg length differential. DESIGN: Repeated prone and supine
      measurements of leg length inequality were made by an experienced chiropractor
      and compared with iliac crest and femur head measurements made on X-rays of
      standing patients. Multiple regression analysis was performed. SETTING: Private
      chiropractic practice. PARTICIPANTS: The first 50 new patients with low back pain
      that were X-rayed were included in the study. RESULTS: Intraexaminer reliability
      was excellent for the prone measurements. The supine tests were less reliable.
      The prone measurements were highly correlated with the standing X-ray femur head
      measurement. The supine measurements were poorly correlated. Measurements of
      deficiency at the iliac crests on X-ray were most highly correlated with X-ray
      measurements of discrepancy. In multiple regression, the prone measurements and
      duration of problem were the only significant predictors of standing X-ray
      difference. CONCLUSIONS: In this study, crest measurements were made on X-ray;
      the degree of accuracy with which millimeter differences can be measured
      clinically on patients is unknown. In a few cases, the supine measurements were
      more accurate than the prone; however, the supine test validity was poor when
      compared with the standing X-ray measurements, and reliability was less than
      expected. Supine measurements should not be used to estimate standing leg length
      discrepancy in new low back pain patients but perhaps can be used in other
      clinically meaningful ways. Intraexaminer reliability of the prone measurements
      was higher, but further investigations need to focus on interexaminer
      reliability. The prone measurement as a predictor holds promise, but new
      measurement tools must be developed.

PMID- 8568427
TI  - The immediate effect of activator vs. meric adjustment on acute low back pain: a
      randomized controlled trial.
AB  - OBJECTIVE: To compare the immediate effects on pain of Meric and Activator
      adjustments in patients with acute low back pain (LBP). DESIGN: Adjustments were
      compared using a randomized, controlled clinical trial for relative
      effectiveness. SETTING: The study was conducted at a private chiropractic clinic
      in Tulsa, Oklahoma. PATIENTS: Thirty consecutive established patients presenting
      with acute LBP were studied. Sixteen subjects were randomly assigned to the Meric
      group and 14 to an Activator group. The mean (SD) age was 53.5 (9.5) for the
      Activator group and 51.8 (10.3) for the Meric group. INTERVENTION: The subjects
      received either a single Meric or Activator adjustment to the posterior joints
      involved. MAIN OUTCOME MEASURES: Before and immediately after the adjustments,
      subjects rated their pain intensity on a visual analog pain scale. RESULTS: The
      mean reduction in pain for the Activator group was means = 22.2, SD = 21.7; for
      the Meric group means = 21.8, SD = 21.5. The results indicate that there is no
      significant difference between Meric and Activator adjustments in reducing acute
      LBP (F = .005, df = 2, 27, p = .941). CONCLUSION: This study demonstrated no
      advantage of one procedure over the other for the reduction of pain.

PMID- 8568428
TI  - Smoking and low back pain: is the association real?
AB  - STUDY DESIGN: A review was made of the epidemiological literature on the
      association between smoking and low back pain (LBP). OBJECTIVES: The first
      objectives was to identify studies that challenged their preliminary results with
      additional test factors and to see what effect this had on the outcomes. The
      second objective was to identify test factors that were unique to studies in
      which the original association disappeared after multivariate analysis. SUMMARY
      OF BACKGROUND DATA: The literature on this subject is confusing and no systemic
      investigation seems to have been made on the possibility of spurious data
      interpretation. METHODS: Twenty-four articles reporting on 126 epidemiological
      studies (in 24 reports) on the association between smoking and LBP were
      systematically reviewed by the authors, independently and jointly. RESULTS: In
      eight of the thirteen studies that tested a preliminary positive association
      between smoking and LBP, this association remained after multivariate analysis,
      whereas it disappeared in after analysis in five. Two variables, marital status
      and occupation, were uniquely present in some of the studies in which the initial
      positive association was lost. However, their study samples were probably
      nonrepresentative of the general population. CONCLUSIONS: A more strategic
      approach is needed in the study of the role of extraneous factors. In particular,
      marital status and occupation should be further investigated.

PMID- 8568429
TI  - Modeling a chiropractor:population ratio.
AB  - OBJECTIVE: As the cost of disability from musculoskeletal conditions increases,
      more attention needs to be directed toward the number of health care
      practitioners required to effectively treat these problems. This study describes
      a methodology to estimate the number of chiropractors needed to effectively serve
      a given population. DATA SOURCES: The data on the utilization of chiropractic
      services over time comes from the Saskatchewan Medical Care Insurance Branch.
      STUDY SELECTION: A Medline search was performed using these key words:
      musculoskeletal, back pain, neck pain, headaches and prevalence. Chiropractic
      journals were reviewed for the analysis of the kinds of conditions treated by
      chiropractors. DATA SYNTHESIS: Saskatchewan data shows a steady increase in the
      percentage of the population treated by chiropractors in response to an increase
      in the number of chiropractors. A regression function was defined using the
      number of chiropractors as the independent variable and the number of patients
      treated annually as the dependent variable, where all Saskatchewan patients with
      musculoskeletal conditions could be treated by chiropractors. CONCLUSION: Of the
      general population, 36.1% annually suffer from some sort of musculoskeletal
      problem. In Saskatchewan, this means that 366,848 people could be treated by
      chiropractors if enough chiropractors were available. Saskatchewan needs 391
      chiropractors to effectively serve the musculoskeletal problems of the general
      population. This is an ideal chiropractor:population ratio of 1:2,588. Health
      care policymakers should design incentives to channel the appropriate patients
      into chiropractic offices.

PMID- 8568430
TI  - Cervical spondylotic myelopathy.
AB  - OBJECTIVE: To present the clinical and neurological features of a patient
      suffering from cervical spondylotic myelopathy. CLINICAL FEATURES: Cervical
      spondylotic myelopathy (CSM) is a condition in which the vascular and neural
      structures are compressed by bony spurring and soft tissue hypertrophy, causing
      ischemic damage to the spinal cord. Although cervical spondylotic myelopathy is
      the most common cord disorder in older adults, the diagnosis is often missed
      because the initial symptoms are subtle and the condition usually presents with
      associated conditions such as nerve root involvement. INTERVENTION: The patient
      was referred to a neurosurgeon for a posterior decompressive laminectomy. The
      advancing symptoms of CSM were apparently halted by the surgery in this case,
      until complication from a fall resulted in quadriplegia. CONCLUSION: Appropriate
      testing can aid differential diagnosis of the condition and expedite appropriate
      management of the condition. Treatment may include surgical cervical
      decompression of the involved area. An untreated progressive spondylotic
      myelopathy may cause permanent neurological damage to the spinal cord. Attention
      should be paid to the clinical signs and treatment of this underdiagnosed
      condition.

PMID- 8568431
TI  - The dental-chiropractic cotreatment of structural disorders of the jaw and
      temporomandibular joint dysfunction.
AB  - OBJECTIVE: To present a case demonstrating the concept of integrated dental
      orthopedic and craniochiropractic care for treating structural disorders of the
      jaw, neck and spine. CLINICAL FEATURES: A 33-yr-old woman sought orthodontic
      therapy for an overbite and severe crowding of the lower teeth. She reported a
      history of bilateral headaches and jaw popping. Orthodontic examination revealed
      degenerative changes in the right temporomandibular joint and restricted jaw
      opening. While in treatment, the patient began to experience severe
      temporomandibular joint pain and neck/lower back pain, which convinced her to
      accept chiropractic care. Initial chiropractic sacro-occipital technique (SOT)
      evaluation found Category II weight-bearing instability of the sacroiliac joint,
      specific thoracic and cervical vertebral subluxations, cranial sutural
      restrictions and temporomandibular dysfunction. Cervical X-rays revealed absence
      of the anterior cervical curve, characterized by parallel vertebral base lines.
      INTERVENTION AND OUTCOME: In addition to orthodontic treatment, the patient also
      received semiweekly (then bimonthly) adjustments of the spine, neck and cranial
      sutures. The cotreatment approach eliminated pain while improving head, jaw and
      tooth position. CONCLUSION: The position of the jaw and head and neck are
      intricately linked. The acute symptoms experienced during the initial dental
      treatment phase were caused by the inability of the head and neck to adapt to
      maxillary and mandibular changes. Chiropractic treatments enabled the body to
      respond positively to the dental changes. As the mandibular position improved,
      further improvements were indicated by physical testing and X-rays.

PMID- 8568432
TI  - The validity of thoracolumbar paraspinal scanning EMG as a diagnostic test:
      examination of the current literature.

PMID- 8568433
TI  - How to evaluate intraexaminer reliability using an interexaminer reliability
      study design.

PMID- 8568434
TI  - How to evaluate intraexaminer reliability using an interexaminer reliability
      study design.

PMID- 8568435
TI  - "Playing God": religious symbols in public places.

PMID- 8568436
TI  - "Playing God" and invoking a perspective.
AB  - The article sorts through some uses of the phrase "playing God," finding that the
      phrase does not so much state a principle as invoke a perspective, a perspective
      from which scientific and technological innovations are assessed. It suggests the
      relevance of a perspective in which "God" is taken seriously and "play"
      playfully.

PMID- 8568437
TI  - "Playing God" and germline intervention.
AB  - The phrase "playing God" so popular with journalists takes on a serious meaning
      in the debate over germline genetic intervention. While guarding against the
      dangers of human pride implied in the phrase "playing God," special attention is
      given here to the Christian concept of the human being as created in the divine
      image, the imago dei. Human beings are dubbed "created co-creators." In this
      light ethical arguments proscribing germline intervention are examined and
      refuted, leaving the door open for creative responsibility on the part of the
      present generation for our future progeny.

PMID- 8568438
TI  - Human action and God's will: a problem of consistency in Jewish bioethics.
AB  - The religious legitimacy of medical practice was an issue of serious contention
      amongst medieval Jewish scholars. For Nahmanides, altering the patient's fate
      through manipulation of natural causality amounts to circumventing divine
      judgment. For Maimonides, however, human accomplishment is part of God's
      providential design; this view generally prevails in contemporary Jewish
      bioethics. But the doctrine of deligitimizing human intervention continues, even
      while unacknowledged, the underlie certain contemporary positions. These include
      arguments within Jewish bioethics about end-of-life decisions, which are
      therefore imbued with inconsistencies. It is suggested that, given the overall
      endorsement of modern medicine, the Nahmanidean approach must be explicitly
      confronted.

PMID- 8568439
TI  - "Playing God" and the removal of life-prolonging therapy.
AB  - "Playing God" is the charge frequently leveled when physicians and patients agree
      to withdraw life-sustaining medical treatments and let the patient die. The
      accusation rings hollow in the context of four hundred years of moral reflection
      on the duty of an individual to undergo medical treatments to preserve life. From
      the teachings of Soto and Banez in the 16th century through the President's,
      Commission 1983 report 'deciding to forego life-sustaining treatments' there is a
      clear and constant teaching that though life is sacred it is not an absolute and
      our moral duty to preserve it is limited and based on rational reflection. No
      patient need undergo any treatment of procedure that is "disproportionately"
      costly, burdensome, or painful. The assessment of whether to accept or reject a
      proposed treatment is in part subjective and belongs to the individual patient.
      The only remaining issue is how to make that judgement for those unable to speak
      for themselves.

PMID- 8568440
TI  - The new reproductive technologies: defying God's dominion?
AB  - Objections that the New Reproductive Technologies pose temptations to "play God"
      are common. This essay examines three versions of the objection: 1) these
      technologies "usurp God's dominion in reproduction"; 2) they permit us to "make"
      our offspring; and 3) they involve us in a denial of human finitude. None proves
      to generate a decisive case against the New Reproductive Technologies; each
      requires some further argument to be persuasive. Nonetheless, warning not to
      "play God" are shown to have an important parenetic function in the debate over
      medically-assisted reproduction, occasioning needed reflection on the meaning of
      creatureliness, finitude and responsible co-creation in the context of new forms
      of reproduction.

PMID- 8568441
TI  - Back to the basics: reflections on moral discourse in a contemporary Hindu
      community.
AB  - Instead of searching through Hindu sources for appropriate insights into the
      questions related to "playing God" in biomedicine, the author seeks rather to
      understand why some Hindus at least are not inclined to ask such questions. Using
      examples from the Srivaisnava sect of south India, the author shows how
      Srivaisnava Hindus focus primarily on character formation and the practice of the
      virtues encoded in the classical texts, thereafter leaving it to the individual
      to "act as he or she will" in the world outside the community-a world which is
      neutral vis a vis religious values, neither governed by such values nor able to
      instigate the adjustment of religious values to fit changing times. The question
      then becomes, "What do modern ethicists have to learn from the moral discourse of
      the Srivaisnava community."

PMID- 8568442
TI  - The paracoronal (marginal) cells of fungiform papilla of Rana esculenta.
AB  - Paracoronal secretory cells can be observed outside the sensorial area of the
      fungiform papilla of Rana esculenta. The morphology of these cells, the type of
      secretion and their function have, to date, only been incidentally described. By
      scanning electron microscopy (SEM), the paracoronal cells appear as swallow's
      nest-shaped formations with openings 10-15 microns in diameter. The walls of
      paracoronal cells are characterized by laminar processes subdividing the interior
      hollow. The cavity of these formations is occupied by amorphous material as
      demonstrated by light microscopy (LM) pictures. The secretory material fills 7/8
      of the upper part of the cytoplasm and appears rather transparent. The secretory
      material is PAS-negative, unlike the secretory granules contained in laminar
      processes. By transmission electron microscopy (TEM), they appear as clear ovoid
      structures, the nucleus of which is situated in the deeper part of the cell,
      enveloped by a thin cytoplasmic layer and characterized by secretory apparatus
      and the presence of secretory granules of middle electron-opacity. The apical
      part of these cells presents large mucous droplets. These cells adhere both to
      ciliated and parietal cells. Following cytochalasin-B treatment, cells do not
      show any considerable ultrastructural modification, while after terbutaline
      treatment the profiles of secreted paracoronal cells increase greatly.
      Histochemical properties of their secretory products are similar to those of
      parietal cells and their particular anatomical localization may exclude the
      direct implication of these cells in taste transduction.

PMID- 8568443
TI  - Salt-dependent structural changes of chromatin in isolated chicken liver nuclei
      as visualized by scanning electron microscopy.
AB  - MgCl2- and KCl-dependent structural changes of chromatin in isolated chicken
      liver nuclei were examined by scanning electron microscopy. In the absence of
      salts, the chromatin appeared as granular or knobby fibrillar structures, 15-30
      nm in diameter. At 0.2 mM MgCl2, the structures condensed into 30-60 nm fibers.
      At 2 mM MgCl2, most chromatin was present as condensed chromatin masses. Above 50
      mM MgCl2, the condensed chromatin masses were loosened. At KCl concentrations
      higher than 25 mM, the chromatin appeared as discrete 30-60 nm fibers. However,
      no condensed chromatin masses were formed at any of the KCl concentrations
      examined in this study. These results indicate that the MgCl2- or KCl-dependent
      transitions from a lower to a higher level of chromatin organization in the
      isolated nuclei are comparable to those reported in isolated chromatin fragments,
      and that KCl is ineffective in the formation of condensed chromatin.

PMID- 8568444
TI  - Ultrahigh-resolution low-voltage SEM reveals ultrastructure of the glucan network
      formation from fission yeast protoplast.
AB  - The refined field emission SEM, S-900 LV which gives better resolution especially
      at low voltages below 5 kV was developed for ultrahigh resolution scanning
      electron microscopy. A visualization test at x 300,000 was made using a gold
      evaporated magnetic tape, and the resolution was found to be about 1 nm at 2.5
      kV. The ultrastructure of the cell wall, especially the reverting glucan network,
      from the protoplast of Schizosaccharomyces pombe was studied using this improved
      ultrahigh-resolution low-voltage SEM (UHR-LVSEM). The results with uncoated
      reverting protoplasts observed with this microscope revealed that the network was
      originally formed as secreted particles scattered on the protoplast surface and
      these were subsequently stretched to microfibrils about 2 nm thick. The
      microfibrils were twisted around each other and joined together so that they
      developed into 8-nm-thick fibrils, forming a ribbon-shaped network of glucans
      about 16-nm-thick which covered the entire protoplast surface. The UHR-LVSEM
      images of reverting protoplasts treated with glucanase confirmed that the
      particles scattered on the protoplast surface in the initial stage of
      regeneration were glucan in nature.

PMID- 8568445
TI  - Scanning tunneling microscopic study of osmium-impregnated collagen.
AB  - The vapor-phase osmium impregnation method was applied to increase the
      conductivity of the collagen specimens used in scanning tunneling microscopy
      (STM), since the application of STM to biological materials has been limited by
      the poor conductivity, irregular sample geometry, and instability of these
      materials. The impregnation method was applied to collagen fibrils attached to
      highly oriented pyrolytic graphite, and the STM images obtained were compared
      with those of routinely processed uncoated specimens. The osmium-impregnated
      collagen fibrils showed a periodicity of about 67 nm, which was also observed on
      the negative-stained specimens by transmission electron microscopy. In addition,
      the periodicity of 3.1 nm, which corresponded to the helical cycle of the 3 alpha
      chains within collagen, was clearly demonstrated by STM. Moreover, the
      comparative observations of collagen specimens without osmium impregnation
      disclosed the left-handed helical structure with a periodicity of 3.1 nm in a
      single collagen filament.

PMID- 8568446
TI  - Ultrahigh-resolution scanning electron microscopy of MDCK cells infected with
      influenza viruses.
AB  - Ultrahigh-resolution scanning electron microscopy of MDCK cells infected with
      influenza viruses was carried out by the uncoated uranyl acetate staining
      preparation method. Ridge-like protrusions were detected on virus particles and
      were considered to be an indication of aggregated glycoprotein spikes. Bundles of
      filamentous virus particles along with bacillary virus particles were encountered
      on MDCK cells infected with freshly isolated strains of type A virus. Filamentous
      virus particles that were twisted like ropes were observed on MDCK cells infected
      with strains of type B virus.

PMID- 8568447
TI  - Energy-dispersive X-ray microanalysis of calcified tissues after NaOCl treatment
      and/or resin embedding.
AB  - By energy-dispersive X-ray microanalysis (EDX) in scanning electron microscopy,
      we studied the calcification of the inner-basic lamellas of a cow bone and the
      coronal cementum of a horse tooth treated with sodium hypochlorite (NaOCl). These
      tissues were divided into 4 groups with a combination of NaOCl treatment and
      polyester-resin embedding including, [A]: non-NaOCl + Resin, [B]: non-NaOCl + non
      resin, [C]: NaOCl + Resin, and [D]: NaOCl + non-Resin. From the Ca and P values
      by EDX analysis, it was suggested that the natural porous spaces of [B] were
      higher than those of [A], and both the natural and NaOCl-soluble porous spaces
      were highest in [D]. However, [A] had the lowest porous spaces in both the
      tissues because the micropores formed 3-dimensionally by NaOCl treatment might be
      incompletely filled with the resin. The backscattered electron microscopy and the
      difference of the Ca/P ratios indicated that the NaOCl treatment of the calcified
      tissues caused some minerals besides organic materials to dissolve. Thus, the
      sample preparation of [B] is suitable for the quantitative EDX of calcified
      tissues, whereas the data of [C] except for the Ca/P ratio may be used to
      approximate the Ca and P contents.

PMID- 8568448
TI  - Capillaries with fenestrae in the rat soleus muscle after experimental limb
      immobilization.
AB  - Capillaries in the rat soleus muscle were examined by electron microscopy 4 weeks
      after limb immobilization and compared to those in untreated muscle. Immobilized
      muscles showed degenerative changes such as dissolution of sarcomeres, vacuoles,
      and a small increase in connective tissues, including collagen fibers, around
      muscle fibers. Eight percent of the capillaries in these muscles were found to
      have fenestrae. The non-nuclear portions of the endothelial cells were extremely
      thin and were perforated by several fenestrae which were bridged by a single
      layered diaphragm. The untreated muscles contained only continuous capillaries.
      These findings suggest that the occurrence of capillaries with fenestrae in the
      immobilized muscle may be a result of structural changes in the muscle.

PMID- 8568449
TI  - Two-dimensional fourier analysis of electron micrographs of human skin for
      quantification of the collagen fiber organization in the dermis.
AB  - Two-dimensional (2-D) Fourier analysis was used to quantify the structural
      organization of collagen fibers in the dermis of the human skin. The 2-D Fourier
      spectra of electron micrographs of collagen fibers contained large amplitude
      Fourier components (1 fundamental and 3 harmonic peaks), representing the
      predominant structural parameter of the fibers, the center-to-center spacing of
      collagen fibrils. The average center-to-center spacing of the collagen fibrils
      was found from the position of the peaks. For a normal fiber of reticular dermis,
      this spacing was 116 nm. The fibril diameter appeared to modulate the peak
      heights.

PMID- 8568450
TI  - Cartilage type II collagen fibrils show distinctive negative-staining band
      patterns differences between type II and type I unfixed or glutaraldehyde-fixed
      collagen fibrils.
AB  - The cross striation of native and reconstituted collagen fibrils is believed to
      conform to a unique D-band pattern independently of the genetically distinct
      types of fibril-forming collagens. This investigation focuses on type II native
      collagen fibrils, whose negative-staining patterns are shown to differ from the
      usual banding exhibited by type I collagen fibrils. Negative staining with
      phosphotungstic acid, pH 7.4, was carried out on a) unfixed and b) glutaraldehyde
      fixed collagen fibrils isolated from bovine hyaline cartilages. The band patterns
      obtained and their microdensitograms were compared to similarly processed type I
      collagen fibrils isolated from bovine fibrous tissues. Only minor differences
      were observed in unfixed fibrils. In the intraperiod light zones of type II
      fibrils, two dark bands (interbands X2-Y4 and Y4-Y2) showed different intensities
      with respect to their homologous bands in type I fibrils. In contrast, a marked
      difference was shown by glutaraldehyde-fixed fibrils. In comparison with type I
      fibrils, the greater stain exclusion capacity of type II fibrils yielded both the
      appearance of supernumerary bands, which altered banding in two intraperiod
      regions, and differences in the intensity of several bands in three intraperiod
      regions where the band distribution was similar. This stain exclusion pattern may
      be accounted for by molecular extradensity. The possibility that it depends on
      linkage with a higher number of glutaraldehyde residues and/or the persistence of
      cross-linked collagenic or non-collagenic proteins is discussed. To refer to the
      glutaraldehyde-induced band patterns in negatively stained type II and type I
      collagen fibrils, the terms "bands GA(II) 1-12" and "bands GA(I) 1-15,"
      respectively, are proposed.

PMID- 8568451
TI  - Further study of mineral deposits at the occlusal fissure of human enamel.
AB  - The large mineral deposits at the macroscopically occluded fissure was
      investigated using a high-resolution electron microscope. The large polygonal
      crystals at the bottom third of the fissure consisting of single crystals were
      mainly whitlockite. The contact between the large crystals was formed in some
      interfaces where the incoherent tilt boundary was formed. The plate-like crystals
      at the middle third of the fissure corresponded with whitlockite and consisted of
      the aggregation of small crystallites positioned in different directions at the
      appositional levels, where the lattice fringes were distorted. These findings
      suggested that two types of large crystals provide a structure which is favorable
      for natural occlusion to occur at the intact fissure.

PMID- 8568453
TI  - Stabilization of biological specimens by the use of plasma polymerized
      hydrocarbon film for imaging with an atomic force microscope.
AB  - An atomic force microscope makes imaging of biological molecules possible at high
      resolution. To this end all samples have to be fixed securely to a flat solid
      support so that they cannot be displaced by the scanning tip. We herein describe
      a new method to fix the biological samples to glass surfaces by depositing a thin
      layer of plasma polymerized methane gas in a high vacuum chamber. Such samples
      can thus be imaged repeatedly by an atomic force microscope without any loss of
      image quality.

PMID- 8568452
TI  - High-resolution electron microscopic study of salivary calculus.
AB  - The present study was performed to examine crystals in salivary calculus by high
      resolution electron microscopy (HREM) and electron diffraction analyses.
      Microradiography (MR) showed that the calculus had three nuclei and showed
      complex shapes and mineralization. Hydroxyapatite (HA), in a variety of sizes and
      distributions, and the intermingling of HA and whitlockite (WH) at well-calcified
      areas, were observed.

PMID- 8568454
TI  - Melanin-concentrating hormone gene-related peptide stimulates ACTH, but not alpha
      MSH, release from the tilapia pituitary.
AB  - Tilapia (Oreochromis mossambicus; teleostei) melanin-concentrating hormone gene
      related peptide (tMgrp) was tested for tropic actions on adenocorticotropin
      hormone (ACTH) and alpha-melanocyte stimulating hormone (alpha-MSH) producing
      cells in the tilapia pituitary gland in vitro. Up to 100 microM synthetic tilapia
      Mgrp (tMgrp) had no effect on alpha-MSH release from tilapia neuro-intermediate
      lobes in a superfusion set up. However, at concentrations above 1 microM, tMgrp
      concentration dependently stimulated ACTH release from tilapia anterior lobes.
      This is the first evidence that Mgrp modulates ACTH release from teleost
      corticotropes, and this might implicate the peptide in the regulation of the
      pituitary-interrenal axis of fish.

PMID- 8568455
TI  - The endocrine regulation of spermatogenesis: independent roles for testosterone
      and FSH.

PMID- 8568456
TI  - Pig uterine luminal fluid contains the developmentally regulated neurotrophic
      factor, pleiotrophin.
AB  - The pig conceptus produces a non-invasive placenta which is probably dependent on
      uterine secretory products during both the pre- and post-attachment periods.
      Since some of these factors are also produced during the oestrous cycle, uterine
      luminal flushings (ULF) from adult nonpregnant pigs were analysed to identify
      potentially important maternally-secreted growth factors or cytokines. ULF
      contained several proteins that were detected on Western blots by an antibody
      raised against the N-terminal 14 amino acids of rat pleiotrophin (PTN). One of
      the proteins co-migrated on SDS-PAGE gels and co-eluted from heparin-affinity
      columns with 18 kDa recombinant human PTN, suggesting its identity as the intact
      native porcine PTN (pPTN) molecule. Additional immunoreactive forms of pPTN were
      identified that were of lower molecular mass (14-16 kDa), had lower heparin
      affinities, were more hydrophobic, and were apparently C-terminally truncated.
      Native pPTN was isolated from ULF using cation-exchange chromatography, heparin
      affinity fast protein liquid chromatography and C4 reverse-phase high performance
      liquid chromatography. Structural analysis of the purified protein resulted in
      definitive identification of 15 out of 17 N-terminal amino acids; these were 100%
      conserved with the corresponding residues of human, bovine and rat PTN. These
      results demonstrate various biochemical properties of pPTN and suggest that, in
      addition to the apparent involvement of PTN in differentiation during early
      neonatal life, it may be delivered in uterine secretory fluids to, as yet,
      undefined target cells in the reproductive tract of the adult female.

PMID- 8568457
TI  - Cloning of glucocorticoid-regulated genes in C6/ST1 rat glioma phenotypic
      reversion.
AB  - The C6 rat glioma cell line is response to glucocorticoid hormones. C6 variants
      that are hyper-responsive (ST1) and resistant (P7) to hormone treatment have been
      derived previously. Glucocorticoid treatment of ST1 cells leads to complete
      reversion of the transformed phenotype and loss of tumorigenic potential.
      Production of C type retrovirus particles is also induced by glucocorticoids in
      ST1 cells. Cloning of the genes regulated by glucocorticoids in this cell system
      was used here as a strategy to uncover the gene products involved in the
      transformed-to-normal phenotypic change. Construction of a cDNA library from
      glucocorticoid-treated ST1 cells and screening by differential hybridization
      resulted in the isolation of three cellular sequences that code for rat
      metallothioneins (C27 and C41) and alpha 1-acid glycoprotein (C36). Northern blot
      analysis revealed that expression of these genes was dramatically induced by
      hydrocortisone in ST1 but not in P7 cells. Viral genomic RNA was used to isolate
      and characterize retrovirus-related sequences that could also be responsible for
      the phenotypic reversion phenomenon.

PMID- 8568458
TI  - Prolactin release from subpopulations of rat lactotrophs in the presence and
      absence of dopamine.
AB  - In this study we examined the effects of dopamine (DA) and its withdrawal on in
      vitro prolactin (PRL) release from subpopulations of lactotrophs from two regions
      of the anterior pituitary obtained from untreated ovariectomized (OVX) rats or
      OVX rats treated with estrogen, progesterone or a combination of the two.
      Anterior pituitaries were cut horizontally into an inner (dorsal) zone and an
      outer (ventral) zone. Each of these regions was enzymatically dispersed and the
      resulting cells were otherwise untreated (unseparated) or centrifuged through a
      discontinuous Percoll gradient to separate the cells into two subpopulations
      (light and heavy cells). Each of these types of cells was perifused for 1 h with
      culture medium containing 1 microM DA followed by medium devoid of DA for 1 h.
      Prolactin released into the perifusion medium, collected as 5-min fractions, was
      measured by radioimmunoassay and normalized to the number of lactotrophs in the
      cellular pools as determined by immunocytochemistry. In the presence of DA, PRL
      release from unseparated cells of the outer zone was significantly increased by
      estradiol treatment compared with the release from similar cells from OVX rats.
      (Differences were considered significant where P < 0.05.) However, no effect of
      estradiol treatment was observed with unseparated cells of the inner zone or
      light or heavy cells from either zone. Progesterone had no effect on any cell
      type when administered alone. However, when progesterone was given following
      estradiol, PRL release from unseparated cells of the inner zone was increased
      significantly compared with similar cells from the other steroid-treated groups.
      Similar significant increases were observed with light and heavy cells of the
      outer zone, but there was no effect of the combined steroid treatment on light or
      heavy cells from the inner zone. When DA was withdrawn, prolactin release was
      significantly increased from all cells except unseparated cells of the outer zone
      of OVX rat pituitaries. However, when the cells of the outer zone from OVX rats
      were separated into light and heavy cells, they responded to the withdrawal of DA
      with significant and equivalent increases in prolactin release. Light cells of
      the inner zone of pituitaries from OVX rats were more responsive to DA withdrawal
      than were heavy cells. Estradiol increased the response to the withdrawal of DA
      by light and heavy cells of the outer zone and heavy cells of the inner zone.
      Progesterone significantly reversed these effects of estradiol on separated
      cells. These results suggest that lactotrophs in two regions of rat pituitaries
      respond differently to dopamine and to its withdrawal, that subpopulations of
      lactotrophs within these regions also respond differently and that steroids
      modulate these responses.

PMID- 8568459
TI  - IGF-II and IGF-binding proteins increase dramatically during rabbit pregnancy.
AB  - During pregnancy, changes in the IGF axis are associated with changes in maternal
      metabolism and nutrient repartitioning which are necessary to meet the demands of
      a growing conceptus. The aim of this study was to assess the IGF axis, maternal
      weight changes and food intake in female New Zealand White rabbits (n = 7) prior
      to breeding (day 0) and serially throughout pregnancy until term (day 30-31). The
      total weight of the pregnant does progressively increased from 4.03 +/- 0.06 kg
      (mean +/- S.E.M.) on day 0 to 4.47 +/- 0.07 kg on day 30 (P < 0.001). Maternal
      tissue mass (total weight minus estimated conceptus weight) increased until day
      18, plateaued to day 22/23, and then significantly declined. On day 30, the
      maternal tissue mass was not significantly different from the non-pregnant value,
      such that the final increase in total weight was due to conceptus growth.
      Although the does were fed ad libitum, food intake did not change until day 29
      when it decreased to approximately 50% of previous intake (P < 0.01). Maternal
      serum IGF-I was 499 +/- 32 ng/ml on day 0, reached a peak of 832 +/- 160 ng/ml on
      day 21 (P < 0.02), and then declined to 341 +/- 49 ng/ml on day 30. In contrast,
      serum IGF-II increased dramatically from a non-pregnant level of 85 +/- 14 ng/ml
      to 16,295 +/- 2488 ng/ml on day 23 (P < 0.001), and then rapidly declined (3335
      +/- 954 ng/ml, day 30). Changes in serum IGF-binding proteins (IGFBPs) followed a
      pattern similar to IGF-II, as assessed by Western-ligand blotting. All IGFBPs,
      especially the 45-40 kDa IGFBP-3 doublet, increased dramatically between days 12
      and 24 of pregnancy, and then declined towards term. In conclusion, we observed
      unique and dramatic changes in the maternal serum IGF axis that corresponded to
      periods of maternal weight gain and loss. The tissue source of IGFs and IGFBPs
      remains undetermined, although it is of note that the time when major changes in
      the IGF axis were first observed coincided with the time of functional change
      from yolk sac to placenta in the rabbit.

PMID- 8568461
TI  - Interleukin-1 effect on glycemia in the non-obese diabetic mouse at the pre
      diabetic stage.
AB  - Cytokines, particularly interleukin 1 (IL-1) and tumor necrosis factor, are known
      to induce hypoglycemia in normal rodents or different experimental models of type
      II diabetes. We investigated, at the pre-diabetic stage, the effect of short-term
      administration of murine recombinant interleukin-1 alpha (mrIL-1 alpha) on the
      levels of glucose, insulin and corticosterone in the non-obese diabetic (NOD)
      mouse, a spontaneous model of type I diabetes. Two-month-old, pre-diabetic NOD
      mice of both sexes were insensitive to mrIL-1 alpha (12.5 and 50 micrograms/kg) 2
      h after administration, the time at which the maximal decrease (around 50%) was
      observed in the C57BL/6 mouse strain. Kinetic studies however showed that mrIL-1
      alpha lowered glycemia in both sexes of NOD mice, but the effect was limited and
      delayed. In the NOD and C57BL/6 strains, mrIL-1 alpha had no influence on insulin
      levels in females, but significantly increased them in males (P < 0.0001).
      Castration of NOD males abrogated the stimulatory effect of mrIL-1 alpha on
      insulin secretion. Corticosterone secretion was stimulated by mrIL-1 alpha in
      both sexes of NOD and C57BL/6 mice, and this effect was faster and greater in NOD
      females than in C57BL/6 females. The incomplete hypoglycemic response to mrIL-1
      alpha in females may be attributed to the anti-insulin effect of glucocorticoids,
      an effect which can be demonstrated when mrIL-1 alpha is administered to
      adrenalectomized animals or when mrIL-1 alpha is administered together with the
      glucocorticoid antagonist RU38486. In NOD males, in contrast, glucocorticoids did
      not play a major role in the limited hypoglycemic response to mrIL-1 alpha, since
      RU38486 and adrenalectomy were not able to unmask a hypoglycemic effect.
      Moreover, NOD mice of both sexes were less sensitive than C57BL/6 mice to the
      hypoglycemic effect of insulin (2.5 U/kg), which suggests some degree of insulin
      resistance in NOD mice. With regard to the effect of IL-1 on NOD mouse glycemia,
      therefore, these results suggest that glucocorticoids and/or androgens, according
      to the animal's sex, may induce a state of insulin-resistance.

PMID- 8568460
TI  - Inhibition of agonist-mediated calcium entry by calmodulin antagonists and by the
      Ca2+/calmodulin kinase II inhibitor KN-62. Studies with thyroid FRTL-5 cells.
AB  - Calmodulin and calmodulin-dependent mechanisms are probably important in
      regulating thyroid cell function. However, calmodulin antagonists may directly
      modify calcium fluxes in cells. In the present investigation the effects of
      several calmodulin inhibitors and of KN-62, a specific calcium/calmodulin kinase
      II inhibitor, on the ATP- and thapsigargin-evoked changes in intracellular free
      calcium ([Ca2+]i) were investigated in Fura-2 loaded thyroid FRTL-5 cells. All of
      the inhibitors tested attenuated agonist-evoked calcium entry. The inhibitor
      calmidazolium per se potently released sequestered calcium followed by enhanced
      calcium entry. Pretreatment of the cells with calmidazolium inhibited both the
      thapsigargin-and the ATP-evoked calcium entry. Our results show that calmodulin
      antagonists are potent inhibitors of calcium entry in thyroid cells, possibly by
      directly inhibiting the calcium entry pathway. This inhibition may explain, in
      part, the results obtained with calmodulin inhibitors in previous studies.

PMID- 8568462
TI  - Opioid receptor activation resets the hypothalamic clock generating growth
      hormone secretory bursts in the rat.
AB  - Plasma growth hormone (GH) concentrations were measured serially every 20 min for
      6 h in unrestrained chronically-catheterised male rats to define physiological GH
      pulsatile secretory patterns. Bursts of GH secretion lasted 69 +/- 5 min and
      occurred every 177 +/- 4 min. Intravenous administration of the opioid receptor
      agonist morphine (200 micrograms/kg) caused an immediate GH burst of normal
      duration (63 +/- 3 min) in all animals. This burst of secretion occurred whatever
      the phase of the background GH cycle and was followed by normal trough GH levels;
      a second GH burst occurred 177 +/- 6 min later, an inter-burst period not
      different from controls. Opioid receptor blockade with naloxone (5 mg/kg)
      administered i.v. every 20 min during spontaneous GH bursts significantly
      lengthened the interburst interval from 177 +/- 4 to 200 +/- 9 min (P = 0.015).
      Naloxone did not affect synchronisation of the GH rhythm induced by morphine but
      lengthened the duration of GH secretory bursts from 69 +/- 5 to 94 +/- 9 min (P =
      0.017). The findings indicate that opioid receptor activation resets the
      hypothalamic mechanism generating pulsatile GH secretion and that both the period
      of the GH rhythm and duration of the GH burst is normally shortened by opioid
      mechanisms.

PMID- 8568463
TI  - Inhibitory effect of increased photoperiod on wool follicle growth.
AB  - The relationships between circulating prolactin (PRL), wool follicle growth and
      daylength were investigated in 24 New Zealand Wiltshire ewes housed indoors from
      September 1989 to May 1991. Twelve control (C) ewes were maintained under natural
      photoperiod. Two other groups were held in short days (SD; 8 h light: 16 h
      darkness) commencing from the winter solstice (22 June 1990) for either three
      (group SD3, n = 7) or six (group SD6, n = 5) months before reversion to natural
      daylength. Skin was sampled at one- to four-week intervals for histological
      determination of percentages of growing primary and secondary follicles. Hourly
      blood samples over 24 h were collected via jugular cannulae from C sheep in March
      and July and then monthly from all animals until December 1990 for estimation of
      mean monthly PRL concentrations for each treatment group. Between autumn (March
      1990) and winter (July) primary follicle activity (PFA) and secondary follicle
      activity (SFA) declined in C ewes (PFA: 97 to 43%, SFA: 100 to 57%). Follicle
      regrowth during July and August in eight C ewes preceded the initial rise in
      plasma PRL from the winter minimum (1.6 ng/ml). Across the three groups, four
      instances of decreased follicle activity were observed, closely following or
      concurrent with increases in plasma PRL concentrations. The resumption of spring
      growth in four C sheep was temporarily checked by falls in follicle activities
      during September and October as PRL concentrations began to increase (3.4 to 8.9
      ng/ml). Follicle activity also declined in November and December in eight C
      sheep, coincident with the rapid rise in PRL to a seasonal maximum in late
      November (165.4 ng/ml). The increase in SD3 follicle activity over spring was not
      delayed by short days but during October, after release from treatment, PRL
      concentrations rose (1.8 to 12.0 ng/ml) and follicle activity declined (PFA: 65
      to 38%, SFA: 68 to 43%). In SD6 ewes, PRL concentrations were suppressed (2.1
      ng/ml) and relatively constant levels of follicle activity (PFA: 73%, SFA: 95%)
      were maintained throughout short-day treatment. Release of SD6 ewes into summer
      photoperiod in January 1991 temporarily interrupted follicle growth (PFA: 68 to
      17%, SFA: 96 to 19%) and caused out-of-season shedding in March and April.
      Contemporary C follicle activities were high (PFA: 95%, SFA: 98%). These data
      suggest that natural and experimental increases in daylength have a short-term
      inhibitory effect on growing wool follicles which could be mediated through
      rising concentrations of plasma prolactin.

PMID- 8568464
TI  - Thermic effect of food in hypothyroid rats.
AB  - The regulatory and obligatory components of cephalic and gastrointestinal phases
      of the thermic effect of food (TEF) were measured in control and hypothyroid
      rats. A significant decrease (P < 0.05) in regulatory and obligatory components
      of cephalic and gastrointestinal TEF, after either a control or energy-dense
      meal, was found in hypothyroid rats compared with control rats. Our findings
      indicate that hypothyroidism is associated with a decreased thermogenic response
      to food which contributes to the reduced energy expenditure of hypothyroid rats.
      Our results also suggest that tri-iodothyronine is involved in the regulation of
      postprandial thermogenesis directly as well as through its influence on beta
      adrenergic response and insulin release.

PMID- 8568465
TI  - Phospholipase C and adenylate cyclase signalling systems in the action of hCG on
      porcine myometrial smooth muscle cells.
AB  - Although the uterus is a target tissue for LH and its homologue hCG the second
      messenger system responding to LH/hCG in myometrial cells is not established. In
      this study we investigated the involvement of protein kinase A and protein kinase
      C in the action of hCG on porcine myometrial smooth muscle cells in vitro.
      Myometrium was obtained from ovariectomized gilts given 2.5 mg oestradiol
      benzoate plus 50 mg progesterone for five consecutive days. Myometrial cells were
      cultured for 48 h and different doses of hCG were then added. Increasing doses of
      hCG stimulated concentration-dependent increases in [3H]inositol phosphates (IPs)
      accumulation in incubations lasting 24 h. The highest dose of hCG (1000 mU/ml)
      increased turnover of IPs by 2.4-fold as reflected in elevations in IP1, IP2 and
      IP3, and similar effects were observed with noradrenaline. The time- and
      concentration-dependent effects of hCG on IPs accumulation occurred between 16
      and 24 h of incubation. Incubation of myocytes with the lowest doses of hCG (0.1
      and 1 mU/ml) caused a significant increase in cAMP accumulation but the highest
      doses (10-1000 mU/ml) had no effect on cAMP concentrations. This is the first
      demonstration that LH/hCG receptor signalling leads to increased inositol
      phosphate turnover in myometrial cells as well as cAMP generation and it leads to
      the conclusion that both protein kinase A and protein kinase C signalling
      mechanisms are involved in gonadotrophin action in porcine myometrial smooth
      muscle cells.

PMID- 8568467
TI  - Regional differences and up-regulation of progesterone receptors in adipose
      tissues from oestrogen-treated sheep.
AB  - Differing risk factors between men and women for a number of vascular and
      metabolic diseases have been linked to regional obesity. The differences in the
      distribution of adipose tissues between men (abdominal or upper-body obesity) and
      women (gluteal/femoral or lower body obesity) suggest a role for sex steroids in
      the regional distribution of fat. Previous work from this laboratory has shown
      the presence of oestrogen receptor (ER) in gluteal, perirenal and omental adipose
      tissues of ewes with similar physical characteristics to the ER in uterine
      tissue. The concentration profile for adipose ER was gluteal > perirenal >
      omental. In this report, we determined the physiological significance of adipose
      ERs by showing an up-regulation of the progesterone receptor (PR) in adipose
      tissues after oestrogen treatment in a fashion similar to that seen in a major
      responsive tissue such as uterus. Using PR antibodies (PR-6 and C-262), Western
      blot analysis of PR from oestrogen-treated sheep indicated that PR was induced in
      uterus >>> gluteal adipose > perirenal adipose consistent with the concentration
      of ER contained in these tissues. PR could not be detected by Western blotting in
      omental adipose tissue from oestrogen-treated animals or in gluteal, perirenal
      and omental adipose tissues from untreated animals. Sucrose gradient profiles of
      progestin (R-5020) binding from uterus and gluteal adipose tissues of oestrogen
      treated ewes showed specific binding in both the 5S and 9S regions of the
      gradient, while perirenal and omental adipose tissue had only the 5S peak. The
      amount of specific binding was increased with oestrogen treatment in all the
      tissues. When gluteal adipose tissue cytosol was preincubated with PR antibody (C
      262) to prevent binding of ligand and subjected to sucrose gradient analysis,
      both the 5S and 9S regions were diminished, suggesting that both peaks contained
      PR. Dilution of uterine cytosol resulted in an increase in the ratio of the 5S to
      the 9S peak, indicating that the 9S PR complex dissociates at low concentrations;
      this may be the reason why only the 5S peak was observed in perirenal and omental
      adipose tissues. These data offer further support for a direct role of sex
      steroids in regional adipose accretion and metabolism.

PMID- 8568466
TI  - 17 beta-oestradiol enhances the stimulatory effect of 1,25-dihydroxyvitamin D3 on
      alkaline phosphatase activity in human osteosarcoma SaOS-2 cells in a
      differentiation-dependent manner.
AB  - We tested the effect of osteoblastic differentiation on the interactive effects
      of 17 beta-oestradiol (E2) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on alkaline
      phosphatase activity. As cell models we utilized the more differentiated human
      osteosarcoma (SaOS) cells that had been cultured for 6 days in medium containing
      10 nM dexamethasone (Dex) (SaOS+Dex cells) and the less differentiated cells
      cultured in the absence of Dex (SaOS-Dex cells). The cells were challenged with
      1,25(OH)2D3 in the presence or absence of Dex for 24 h and then with E2 for an
      additional 24 h. In SaOS-Dex cells, alkaline phosphatase activity remained
      constant over the 48-h period and was not significantly affected by E2,
      1,25(OH)2D3 or 1,25(OH)2D3+E2 treatment. On the other hand, in SaOS+Dex cells,
      1,25(OH)2D3 and E2+1,25(OH)2D3 stimulated alkaline phosphatase activity (ANOVA, F
      = 154.2, P < 0.0001) with the maximal response at 48 h (P < 0.01). In SaOS+Dex
      cells, 1,25(OH)2D3 had dose-dependent stimulatory effects which were strongly
      enhanced by 10 nM E2 (ANOVA, F = 46.0, P < 0.001). Studies on dose-dependent
      effects of E2, in the presence or absence of 100 nM 1,25(OH)2D3, revealed that in
      the presence of 1,25(OH)2D3, the E2 dose-response curve was biphasic in SaOS+Dex
      cells (ANOVA, F = 3.40, P < 0.005), with maximum stimulation at 10 nM E2 (P <
      0.01). The specificity of E2 was verified using the inactive 17 alpha-oestradiol
      and the oestrogen antagonist, tamoxifen. These data indicate that E2 and
      1,25(OH)2D3 have positive interactive effects on alkaline phosphatase activity in
      human osteoblasts, and suggest that the expression of this interaction is
      dependent on the stage of differentiation of the cells.

PMID- 8568468
TI  - Total amount of circulating human chorionic gonadotrophin alpha and beta subunits
      in first trimester trisomies 21 and 18.
AB  - The aim of this study was to evaluate the variations in the balance between total
      (free and combined) circulating alpha and beta subunits of human chorionic
      gonadotrophin (hCG) in trisomy 21 and 18. Maternal serum samples were collected
      at 10 and 11 weeks of gestation from 22 singleton pregnancies with trisomy 21 (n
      = 17) and trisomy 18 (n = 5) and 66 chromosomally normal controls, matched for
      gestational age. The hCG and free alpha and beta subunits circulating levels were
      measured using specific immunoradiometric assays and converted in a common unit
      system obtained using calibration of the assays with intact and thermally
      dissociated purified hCG preparation. In trisomy 21, the only significant
      difference from controls was in the free beta hCG level which was increased. In
      trisomy 18, intact hCG, free beta hCG as well as total alpha hCG and total beta
      hCG levels were significantly lower whereas the free alpha hCG level was
      significantly higher than in controls. The decrease in total beta hCG was more
      pronounced than the decrease in total alpha hCG resulting in a significant
      increase in the total alpha- to beta hCG subunit ratio in trisomy 18. These
      findings suggest some modifications in the biosynthesis and/or release rates of
      the hCG subunits in these trisomies.

PMID- 8568469
TI  - Arachidonate 12-lipoxygenase in porcine anterior pituitary cells: its
      localization and possible function in gonadotrophs.
AB  - Arachidonate 12-lipoxygenase, which oxygenates positions 12 and 13 of arachidonic
      and linoleic acids, is present in porcine anterior pituitary cells.
      Colocalization of the 12-lipoxygenase with various pituitary hormones was
      examined by immunohistochemical double-staining using antibodies against 12
      lipoxygenase and various anterior pituitary hormones. Under light microscopy,
      approximately 7% of the cells producing luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) were positive for 12-lipoxygenase, whereas the enzyme
      was detected in less than 2% of the cells producing thyrotrophin, prolactin,
      growth hormone (GH), and adrenocorticotrophin. In an attempt to examine the
      participation of 12-lipoxygenase metabolites in pituitary hormone release, we
      incubated the primary culture of porcine anterior pituitary cells with 12
      hydroperoxy-arachidonic acid or 13-hydroperoxy-linoleic acid. Significant
      stimulation of LH and FSH release by these hydroperoxides was observed at 10
      microM in a time-dependent manner. At doses around 10 microM these compounds
      produced responses of similar magnitude to 1 nM gonadotrophin-releasing hormone
      (GnRH), but higher concentrations (30 microM) of the compounds were required for
      GH release. In contrast, 12-hydroxy-arachidonic and 13-hydroxy-linoleic acids
      were almost ineffective. Furthermore, the gonadotrophin release by 1 nM GnRH was
      inhibited by nordihydroguaiaretic acid (a lipoxygenase inhibitor) with an IC50 of
      about 5 microM. Thus, the hydroperoxy (but not hydroxy) products of 12
      lipoxygenase may be involved in the release of pituitary hormones especially LH
      and FSH.

PMID- 8568470
TI  - Thyroid hormone modulates androgen and oestrogen receptor content in the Sertoli
      cells of peripubertal rats.
AB  - A possible role of tri-iodothyronine (T3) on the interplay between testicular
      steroids and Sertoli cells has been investigated on the basis of previous
      findings demonstrating a direct inhibitory influence of T3 on aromatase activity
      and oestradiol production in peripuberal Sertoli cells. In this context, the
      present study was focused on the effects of T3 on oestrogen receptor (ER) and
      androgen receptor (AR) contents in the cytosol and nucleus of Sertoli cells
      isolated from 2-, 3- and 4-week-old euthyroid, hypothyroid and hypothyroid
      treated rats. Hypothyroidism was induced by the oral administration of 0.025%
      methimazole (MMI) from birth until the rats were killed at 2, 3 and 4 weeks of
      age. Half of the MMI-treated animals were injected i.p. with L-tri-iodothyronine
      (T3; 3 micrograms/100 g body weight) during the last week before death. Sertoli
      cells from all groups were initially cultured under basal conditions for the
      first 24 h and subsequently in the presence of testosterone with or without T3
      for an additional 24 h. Hypothyroidism was associated with severe impairment of
      body as well as testicular growth. Euthyroid ERs showed an elevated Kd (0.76 nM)
      which was similar in the different age groups investigated. The in vitro addition
      of T3 or testosterone induced a decrease in ER content and this decrease was
      greater after exposure to both hormones. In 2- and 3-week-old hypothyroid rats,
      ER content was markedly increased and was reversed in euthyroid rats when T3 was
      given in vivo. When ERs were assayed in the Sertoli cell nucleus and cytoplasm of
      2- and 3-week-old animals, a strong relationship in ER content in the two
      cellular compartments was observed. Neither of the hormones tested seemed to
      affect the AR content in the nucleus significantly, while the in vitro addition
      of testosterone or T3 or both hormones together augmented the ARs in the cytosol
      to a greater extent, resulting in an increase in their total (cytosolic and
      nuclear) content in the cells. The present data suggest that T3 down-regulates
      ERs and up-regulates ARs in peripuberal Sertoli cells. The additive effect of
      testosterone and T3 in up-regulating ARs could possibly involve a role for T3 in
      influencing the androgen responsiveness of the Sertoli cells during
      spermatogenesis.

PMID- 8568471
TI  - Plasma levels and molecular forms of proatrial natriuretic peptides in healthy
      subjects and in patients with congestive heart failure.
AB  - A specific and sensitive radioimmunoassay (RIA) for the N-terminal fragment of
      proatrial natriuretic peptide (NproANP) was developed. Antiserum raised in
      rabbits against a mixture enriched with prohormone was 100% cross-reactive with
      human proANP(1-30). Plasma concentrations of proANP(1-30) and ANP
      immunoreactivities (ir-) were simultaneously measured in healthy subjects and
      patients with congestive heart failure (CHF; 26 dilated cardiomyopathy and 5
      ischemic heart disease). High plasma levels of both ir-proANP(1-30) and ir-ANP
      were detected in CHF patients. Circulating ir-ANP levels were elevated in New
      York Heart Association functional Classes II and III patients but not in Class I
      patients. However, plasma levels of ir-proANP(1-30) were higher in asymptomatic
      patients than in healthy subjects, and markedly increased in patients of Classes
      II and III. Analysis of ir-proANP(1-30) by gel filtration chromatography or
      reverse-phase high pressure liquid chromatography revealed a 10 kDa peptide
      circulating as a distinct entity. These findings indicate that: (i) the most
      probable form of NproANP in human plasma is a 10 kDa peptide and (ii) in CHF
      patients the rise in plasma ir-proANP(1-30) levels is more pronounced than the
      variation in plasma ir-ANP. Thus, NproANP plasma levels may prove to be a more
      sensitive marker of left ventricular dysfunction than ANP.

PMID- 8568472
TI  - Expression of tissue inhibitor of metalloproteinases-1 in the human corpus luteum
      after luteal rescue.
AB  - Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a specific inhibitor of a
      group of proteolytic enzymes known as matrix metalloproteinases. These enzymes
      have been widely implicated in the process of tissue remodelling. Extensive
      remodelling occurs in the corpus luteum during luteolysis unless human chorionic
      gonadotrophin (hCG) is produced by the early conceptus. This study aimed to
      investigate the expression and localisation of TIMP-1 in human corpora lutea
      during the luteal phase of the cycle and after luteal rescue with exogenous hCG
      to mimic the changes of early pregnancy. Human corpora lutea from the early (n =
      4), mid- (n = 4) and late (n = 4) luteal phases and after luteal rescue by hCG (n
      = 4) were obtained at the time of hysterectomy. Expression of TIMP-1 was
      investigated in these tissues by Western blotting, immunohistochemistry, Northern
      blotting and in situ hybridisation. Luteal cells of thecal origin were
      distinguished from those of granulosa origin by immunostaining for 17 alpha
      hydroxylase. A 30 kDa protein consistent with TIMP-1 was detected in human
      corpora lutea. This protein was localised to the granulosa lutein cells in all
      tissues examined. TIMP-1 mRNA was found in large quantities in all glands
      examined and this again localised to the granulosa lutein cells. The expression
      and localisation of TIMP-1 did not change throughout the luteal phase and was not
      altered by luteal rescue. The function of this uniform expression of TIMP-1 in
      the corpus luteum is not clear but these data suggest that the inhibition of
      structural luteolysis during maternal recognition of pregnancy is not mediated by
      regulation of TIMP-1 expression.

PMID- 8568473
TI  - Somatostatin does not inhibit prolactin synthesis in normal male rat pituitary
      cells but inhibits prolactin synthesis in estradiol-primed pituitary cells.
AB  - The effects of somatostatin (SRIF) on prolactin (PRL) synthesis and release were
      examined in primary cultured pituitary cells derived from normal and estradiol
      (E2)-primed male rat pituitaries. The cells were continuously incubated in a
      pulse medium containing [3H]leucine with or without 10(-6) mol/l SRIF for a
      period of 15, 30, 60, 180 or 360 min. Following incubation, the medium was
      recovered and the cells were fractionated into cytosolic and granular fractions.
      PRL was isolated by SDS-PAGE and newly synthesized PRL ([3H]PRL) was identified
      by coincident peaks of tritium activities and PRL contents. The specific activity
      (SA, c.p.m./ng), a ratio of [3H]PRL to total PRL, was determined for the
      granular, cytosolic and medium fractions. In control and SRIF-treated groups of
      non-primed pituitary cells, SAs of all three fractions significantly increased
      during the 6-h incubation. Cytosolic and granular SAs showed similar profiles of
      increasing rate in comparison to control. Medium SAs showed a significantly
      higher value in the SRIF-treated group than in the control group only at 180 min.
      These observations indicate that, in the non-primed condition, PRL synthesis is
      not inhibited by SRIF. Medium SAs in the E2-primed group were significantly
      higher than SAs in the non-primed control cells during the initial 3 h of
      incubation, and cytosolic and granular SAs were significantly higher than those
      of the non-primed control during the 3- to 6-h incubation period. These
      observations demonstrate that E2 enhances PRL synthesis and secretion of newly
      synthesized PRL. SRIF treatment of E2-primed lactotrophs resulted in a
      significant decrease in SAs of all three fractions as compared with those of the
      E2-primed control. Our results indicate that in normal male rat pituitary cells
      SRIF does not inhibit PRL synthesis but effectively inhibits PRL synthesis in E2
      primed lactotrophs. This suggests that the inhibitory action of SRIF on PRL
      synthesis is estrogen dependent.

PMID- 8568474
TI  - Evidence for androgen receptor gene expression in human thyroid cells and
      tumours.
AB  - Androgen-binding activity has been identified in normal and pathological
      thyroids, but evidence for the expression of the canonic androgen receptor (AR)
      in the thyroid has not been provided so far. In this study we have used reverse
      transcription (RT)-PCR to examine RNA expression of the canonic AR gene in human
      thyroid tissues, in primary cultures of human thyrocytes and in a variety of
      neoplastic thyroid cell lines (NPA, TPC and WRO). An AR cDNA fragment with the
      expected size of 262 bp was detected in normal tissues and cultured thyrocytes as
      well as in neoplastic cell lines, demonstrating that the gene for AR is indeed
      expressed in thyroid follicular cells. Immunocytochemical analysis revealed the
      presence of the AR protein in cancer cell lines and androgen treatment increased
      nuclear positivity to AR. In a survey of 35 thyroid tissues AR cDNA was detected
      in all the non-neoplastic samples (6 normal and 3 goitrous) and in 19 of 26
      neoplastic samples. AR cDNA was not detected in 4 of the 9 follicular adenomas
      and in 3 of the 12 papillary carcinomas. AR was revealed by immunohistochemistry
      in 1 of 2 normal thyroids, in 1 goiter and in 1 of 2 neoplastic thyroids. These
      findings show the presence of the canonic AR in the human thyroid.

PMID- 8568475
TI  - The proliferative responses of porcine thyroid follicular cells to epidermal
      growth factor and thyrotrophin reflect the autocrine production of transforming
      growth factor-beta 1.
AB  - The present study has investigated an involvement of autocrine transforming
      growth factor-beta 1 (TGF-beta 1) in regulating the proliferative response of
      porcine thyroid follicular cells (TFCs) to epidermal growth factor (EGF) and TSH.
      Primary monolayer TFC cultures exposed to EGF over the range 0-0.4 nmol/l showed
      a dose-dependent increase in [methyl-3H]thymidine incorporation, whereas higher
      EGF doses were associated with a reduction in the level of [methyl-3H]thymidine
      incorporation. TGF-beta immunoneutralisation had little effect on the stimulatory
      action of low EGF doses, but led to an increase in [methyl-3H]thymidine
      incorporation at higher EGF levels. In TFC cultures exposed to TSH, the level of
      [methyl-3H]thymidine incorporation attained at a dose of 1 U TSH/1 was enhanced
      in the presence of TGF-beta 1 antiserum, although the similar stimulatory effect
      of 8-bromo cAMP was unaffected. Treatment of TFCs with phorbol 12-myristate 13
      acetate (8 nmol/l) to activate protein kinase C (PKC) led to an enhanced
      incorporation of [methyl-3H]thymidine which was increased further after
      neutralisation of endogenous TGF-beta 1. While confirming, therefore, a role for
      autocrine TGF-beta 1 in maintaining control of TFC DNA synthesis in vitro, these
      findings provide evidence that an increase in the availability of autocrine TGF
      beta 1 effected by EGF and TSH may play an instrumental role in limiting the
      cellular hyperplasia induced by these factors within the thyroid follicular
      microenvironment. Moreover, the present data also suggest that the availability
      of active autocrine TGF-beta 1 to TFCs under such conditions may be dependent
      upon a PKC-mediated mechanism.

PMID- 8568476
TI  - Leukaemia inhibitory factor in human endometrium throughout the menstrual cycle.
AB  - Leukaemia inhibitory factor (LIF) is a pleiotropic cytokine previously
      demonstrated to be essential for blastocyst implantation in mice. Samples of
      endometrium from normal cyclic women throughout the menstrual cycle were tested
      for LIF messenger RNA by Northern blot analysis and the corresponding protein was
      localised immunohistochemically with a polyclonal antibody to LIF. Western blot
      analysis detected a 45 kDa LIF protein in an extract from late secretory tissue.
      The expression of LIF messenger RNA transcript was detected only during the mid
      and late secretory phases of the cycle after day 20. Immunoreactive LIF was
      observed in all human endometrial samples. In the stroma there were moderate to
      high levels of immunohistochemical staining throughout the cycle with
      considerable variation between individuals but no cyclical variation. Epithelial
      staining, both luminal and glandular, was also present throughout the cycle but
      this was relatively low in the proliferative phase and strongest in the mid to
      late secretory phases. The marked cyclical changes of immunoreactive LIF in the
      human endometrial epithelium suggest a paracrine/autocrine role for LIF in
      endometrial function. Whether LIF is essential for implantation in the human
      remains to be established.

PMID- 8568477
TI  - The android woman--a risky condition.
AB  - Normal women produce small amounts of active androgens. When androgen levels are
      elevated, such as for example in the polycystic ovary syndrome, this is followed
      by the development of male physical characteristics and muscle mass, structure
      and function as well as android adipose tissue distribution and function.
      Psychological features and stress reactions also seem similar to those of men.
      Such women have an increased risk of developing hypertension, non-insulin
      dependent diabetes mellitus and cardiovascular disease. Recent data have shown
      that these physical, and psychological characteristics, as well as risk of ill
      health, are also found in the population of women selected at random. Women in
      the lowest quintiles of levels of sex-hormone-binding globulin--an indicator
      inversely related to active androgens--are at risk of developing hypertension,
      non-insulin-dependent diabetes mellitus and cardiovascular mortality. The
      mechanism probably includes muscular insulin resistance, following a relative
      androgen excess. It is thus apparent that androgens, even within the highest
      levels of the nonselected population of women, are powerful predictors of serious
      disease development. The population at risk might be as large as about 20% of
      middle-aged women. This is an area of female disease risk which requires more
      attention in screening and intervention procedures.

PMID- 8568478
TI  - Gamma, but not alpha, tocopherol levels in serum are reduced in coronary heart
      disease patients.
AB  - OBJECTIVES: Low concentrations of alpha tocopherol are claimed to be associated
      with an increased prevalence of coronary heart disease. This study was undertaken
      to see whether measurements of serum tocopherol concentrations can contribute to
      discrimination between subjects with and without coronary heart disease. SETTING:
      All patients had been referred to the department of cardiology of the University
      Hospital in Uppsala, Sweden. SUBJECTS: Male patients (n = 69) below 60 years of
      age with coronary heart disease (CHD) and healthy age-matched reference subjects
      (n = 138) were compared. RESULTS: Lipid-corrected alpha tocopherol concentrations
      did not differ significantly between the groups, but the CHD group had a lower
      mean concentration of gamma tocopherol and a higher alpha/gamma ratio. In a
      stepwise logistic regression analysis, the LDL/HDL ratio was the best independent
      discriminator between the groups, followed by the proportion of palmitic acid in
      the cholesterol esters and the alpha/gamma tocopherol ratio. CONCLUSIONS: The
      lower gamma tocopherol concentration and the high ratio between alpha and gamma
      tocopherol in the CHD group indicate a difference in antioxidative status between
      CHD patients and healthy subjects. The lipid-lowering treatment of these CHD
      patients is far from optimal.

PMID- 8568479
TI  - Hereditary angio-oedema: new clinical observations and autoimmune screening,
      complement and kallikrein-kinin analyses.
AB  - OBJECTIVES: To study clinical and laboratory manifestations of hereditary angio
      oedema (HAE). SUBJECTS: Thirty-three affected members of a kindred of 63.
      RESULTS: Oedematous attacks in the skin, mucous membranes and gastrointestinal
      tract with fluid displacement were elicited by mental and physical stress, minor
      traumas, dental and surgical procedures, eruption of teeth, tonsillitis,
      pregnancies, and use of oestrogen-containing pills including menopausal
      substitution. Every adult woman with symptomatic HAE (n = 11) showed symptoms of
      urinary tract infections in conjunction with the attacks (P = 0.010), and also
      experienced more spontaneous abortions or premature labours (P = 0.037) than
      healthy relatives. Patients with HAE of both sexes more frequently reported
      heartburn or peptic ulcers (P = 0.002). Rheumatic complaints were reported by 53%
      of HAE patients and 12% of their unaffected relatives (P = 0.013), but
      biochemical screening for 18 autoantibodies and quantitation of immunoglobulins
      did not reveal statistically significant differences between the two groups. C3,
      prekallikrein, total kininogen, high molecular weight kininogen (HK), alpha-2
      macroglobulin and factor XII were not significantly different in HAE patients. In
      contrast, levels of C1-INH and C4 were depressed and cleaved HK increased in
      patients compared to unaffected relatives. CONCLUSIONS: HAE manifests in a
      variety of ways, and may influence risk of spontaneous abortions and premature
      labour.

PMID- 8568480
TI  - Relationships between vitamin D, parathyroid hormone and bone mineral density in
      inflammatory bowel disease.
AB  - OBJECTIVES: To explore the relationships between vitamin D intake, serum
      parathyroid hormone (PTH) and 25-hydroxyvitamin D (250HD) concentrations, and
      bone mineral density (BMD) in inflammatory bowel disease (IBD). SETTING: A
      university hospital clinic in Finland. SUBJECTS: One hundred and fifty randomly
      selected patients with IBD from the hospital register and 73 healthy controls.
      MEASUREMENTS: BMD of the lumbar spine and the proximal femur was measured with
      dual energy X-ray absorptiometry. Vitamin D intake and serum levels of 250HD and
      PTH were determined. RESULTS: The IBD patients had a lower serum 250HD
      concentration (28.4 [SD 12.0] nmol L-1) than the controls (36.1 [16.7] nmol L-1;
      P = 0.001), whereas no differences in the vitamin D intake or the serum PTH
      levels were found. The serum 250HD concentrations and the vitamin D intake of the
      patients with ulcerative colitis (n = 67) were similar to those of the Crohn's
      disease patients (n = 76). The patients with Crohn's disease of the small bowel
      had slightly, but not significantly, lower serum 250HD concentrations (25.6
      [11.0] nmol L-1) than the other Crohn's disease patients (31.4 [14.3] nmol L-1; P
      = 0.061). In the IBD patients, the vitamin D intake and the serum 250HD and PTH
      concentrations were not associated with BMD. CONCLUSIONS: Patients with IBD have
      lower serum levels of 250HD than healthy controls, but similar serum PTH
      concentrations and vitamin D intake. Vitamin D intake, and the serum levels of
      250HD and PTH are not associated with BMD, and malabsorption is unlikely to be a
      major factor in the aetiology of bone loss in unselected IBD patients.

PMID- 8568481
TI  - Autoantibodies against adrenal medulla in type 1 and type 2 diabetes mellitus: no
      evidence for an association with autonomic neuropathy.
AB  - OBJECTIVE: To examine the role of autoimmunity in the development of autonomic
      neuropathy in diabetes mellitus. DESIGN: Retrospective cross-sectional study.
      SETTING: The Department of Medicine, University Hospital, Uppsala, and the
      Department of Endocrinology, University of Lund, Malmo General Hospital, Malmo,
      Sweden. SUBJECTS AND MAIN OUTCOME MEASURES: We examined 135 patients with type 1
      (n = 96) or type 2 (n = 39) diabetes mellitus. Tests for cardiovascular autonomic
      functions were performed, and patient sera were analysed for the presence of
      autoantibodies against the adrenal medulla by indirect immunofluorescence,
      Western blot and immunoprecipitation techniques. RESULTS: Sera from 13% (12/96)
      of the type 1 and 20% (8/39) of the type 2 patients showed a positive cytoplasmic
      immunofluorescence (IF) staining of the adrenal medullary cells, as did 20%
      (30/151) of sera from healthy controls. Fifty-eight and 64% of type 1 and type 2
      patients, respectively, had cardiovascular autonomic neuropathy, but no
      correlation between autonomic neuropathy and positive IF against the adrenal
      medulla was observed, with the exception of significant drops in diastolic blood
      pressure 8 min after tilt (P < 0.005) in type 1 patients. The various IF-positive
      sera reacted with several different proteins when analysed with Western blot
      technique using a total homogenate of the bovine adrenal medulla. These did not
      correspond to any of the proteins involved in the synthesis or storage of
      catecholamines which were considered as putative autoantigens. CONCLUSION: The
      finding of similar frequencies of immunoglobulins binding to adrenal medulla in
      both type 1 and 2 diabetic patients as well as in normal controls, argues against
      a role of anti-adreno-medullary antibodies in the pathogenesis of autonomic
      diabetic neuropathy.

PMID- 8568482
TI  - Serum lipids and lipoproteins are correlated to skin vessel reactivity in healthy
      women.
AB  - OBJECTIVES: To investigate whether serum lipids and lipoproteins are correlated
      to the results of skin vessel reactivity tests. DESIGN: Healthy, non-smoking
      individuals of various ages without atopic constitution and medication were
      selected for the study. SETTING: Subjects blood sampled and examined with
      iontophoresis and a newly developed laser Doppler perfusion imager at Huddinge
      University Hospital. SUBJECTS: Thirteen men, 20-80 years of age, and 21 women, 18
      76 years of age, who fulfilled the inclusion criteria. MAIN OUTCOME MEASURES:
      Normalized perfusion values (%) after iontophoresis of acetylcholine (ACh),
      nitroprusside and isoprenaline. Fasting concentrations of total cholesterol, high
      density lipoprotein cholesterol and triglyceride values. RESULTS: Skin vessel
      reactivity tests to ACh and isoprenaline, and to a lesser extent, nitroprusside
      were positively correlated to high-density lipoprotein cholesterol (HDL-C) levels
      (P = 0.014, 0.005 and 0.113, respectively), and negatively correlated to both the
      ratio of total cholesterol/HDL-C (P = 0.029, 0.011, 0.005) and the level of
      triglycerides (P = 0.045, 0.011, 0.005) in young and middle-aged women. There was
      also a negative correlation between isoprenaline and triglycerides (P = 0.042) in
      elderly women. No correlations between serum lipids and lipoproteins and skin
      vessel reactivity were found in men. CONCLUSIONS: The results of the study
      suggest that serum lipids and lipoproteins, primarily HDL-C, influence skin
      vessel reactivity in healthy women. Furthermore, HDL-C seems to influence the
      function of the vascular smooth muscle as well as the endothelium.

PMID- 8568483
TI  - The incidence of occult cancer in patients with deep venous thrombosis: a
      prospective study.
AB  - OBJECTIVE: This study was undertaken to assess a potential relationship between
      idiopathic deep venous thrombosis (DVT) and occult cancer. DESIGN: Prospective
      study with a 2-year follow-up. SETTING: The Angiology Unit of the First
      Department of Surgery, University of Athens, Greece, a tertiary referral centre.
      SUBJECTS: Two hundred and ninety-three patients with a first episode of
      venographically or Doppler-proved DVT were included in the study, of whom 264
      were followed up for 2 years. INTERVENTIONS: After an initial extensive
      diagnostic workup, including routine blood counts and chemistries, erythrocyte
      sedimentation rate, CEA levels, chest X-ray and abdominopelvic CT scan, all
      patients were closely followed up and periodically examined. MAIN OUTCOME
      MEASURES: The incidence of cancer amongst patients with idiopathic and secondary
      DVT, and the validity of our screening programme. RESULTS: Cancer was diagnosed
      in 21 out of 84 patients with idiopathic DVT (25%) as compared with eight out of
      202 patients with secondary DVT (4%). In 22 out of the 29 cases, cancer was
      detected during the initial admission, and the remaining seven cases were
      detected during follow-up. Cancer was diagnosed in 15 asymptomatic, healthy
      individuals, but only in seven of them was the diagnosis made by CT scan.
      CONCLUSION: Occult cancer is fairly common in patients with idiopathic DVT, but
      the routine use of extensive diagnostic studies for its detection remains to be
      validated by further prospective studies.

PMID- 8568484
TI  - Long-term follow-up of indolent mastocytosis in adults.
AB  - OBJECTIVE: To evaluate the natural course of indolent mastocytosis in adults.
      DESIGN: A retrospective long-term follow-up study. SETTING: The Department of
      Endocrinology of a University Hospital. PATIENTS: Sixteen adult patients with a
      diagnosis of indolent mastocytosis and sufficient biochemical data for
      statistical analysis. One patient had paediatric-onset cutaneous mastocytosis,
      whilst the others had adult-onset systemic mastocytosis. Ages at the end of
      follow-up ranged from 23 to 79, median 50 years. Follow-up periods per patient
      lasted from 13 to 135 months, median 90 months. MEASUREMENTS: Urinary excretions
      of the histamine metabolites N tau-methylhistamine (MH) and N tau
      methylimidazoleacetic acid (MIMA), and signs and symptoms of the disease.
      RESULTS: The excretion of MH but not MIMA increased in four patients (ages 37,
      45, 61 and 65 years) and decreased in two patients (ages 26 and 48 years),
      including the only patient with paediatric-onset cutaneous mastocytosis. The
      excretion of MIMA but not MH increased in none and decreased in one patients (age
      51 years). The excretions of both MH and MIMA increased in one patient (age 23
      years) and decreased in two patients (ages 65 and 79 years). The excretion of MH
      and MIMA can be considered to have been stable in one patient (age 49 years). In
      the five remaining patients, observation periods were rather short. A definite
      judgement on the course of their disease could not be given. In the two patients
      in whom the excretion of both MH and MIMA decreased, the enlarged spleen
      decreased in size, whilst in the other patients, signs and symptoms did not
      change. There were no accompanying myeloproliferative disorders in any patient.
      No special treatment aiming at a reduction in mast cell load has been given.
      Rates of change over the whole follow-up period ranged from -8.4 to +25.1% per
      year. CONCLUSION: The natural course of indolent adult-onset mastocytosis is not
      always progressive. Our data show that the activity of adult-onset indolent
      mastocytosis, as measured by urinary excretion of MH and MIMA and clinical signs
      and symptoms, can substantially decline, especially in older patients.

PMID- 8568485
TI  - Clinical outcome of radioiodine treatment of hyperthyroidism: a follow-up study.
AB  - OBJECTIVES: To study the clinical outcome of treatment of hyperthyroid patients
      with radioiodine. DESIGN: Records of patients treated for hyperthyroidism with
      radioiodine from 1989 to 1992 were examined in 1994, and a questionnaire was sent
      to patients < or = 70 years with Graves' disease (GD) and toxic nodular goitre
      (TNG) to obtain information regarding thyroxine substitution, smoking habits and
      present state of health. SETTING: Outpatients in a thyroid unit; follow-up by
      primary care. SUBJECTS: Seven hundred and fifty-four patients with
      hyperthyroidism treated with radioiodine, 327 receiving the questionnaire, 72%
      response rate. INTERVENTION: Radioiodine treatment using a delivered absorbed
      dose method, aiming at an absorbed dose to the thyroid of 100-120 Gy. MAIN
      OUTCOME MEASURES: Statistical analysis of clinical records and results from
      questionnaire. RESULTS: Only 10% of the patients needed more than one treatment.
      At the time of follow-up, thyroxine supplementation was given to 178 (93%) of the
      GD and to 21 (47%) of the TNG patients. Smoking was more common in GD patients
      than in the general population (44% vs. 26%; P < 0.001). Smoking GD patients
      experienced eye discomfort more often than smoking TNG patients (53% vs. 7%; P <
      0.001). Weight gain after therapy was a problem in 79% of the hyperthyroid
      individuals. CONCLUSIONS: Few patients needed retreatment and most of the GD
      patients had thyroxine after 1-5 years after therapy. Smoking patients,
      especially those with GD, had more eye symptoms. At follow-up, the euthyroid
      patients still consider themselves having a poorer health than individuals in the
      general population.

PMID- 8568486
TI  - Inactivated hepatitis A vaccine in healthy Chinese adults.
AB  - OBJECTIVES: To study the safety, tolerability of and immune response to an
      inactivated hepatitis A vaccine in healthy Chinese adults. DESIGN: Seronegative
      subjects were randomized to receive formalin-inactivated, alum-adjuvanted
      hepatitis A vaccine (25 units, MSD) at 0, 24 weeks (group I) or 0, 2, 24 weeks
      (group II). SUBJECTS: Healthy Chinese adults aged 18 years or above were
      recruited. All subjects were staff of a regional hospital and primary care clinic
      in Hong Kong. MAIN OUTCOME MEASURES: Side-effects, tolerance, seroconversion rate
      and geometric mean titre (GMT) of the two groups were noted and compared.
      RESULTS: Thirty-two and 28 people were recruited into group I and group II,
      respectively. Antibody against hepatitis A developed in 100% of the recipients 1
      month after the last dose of either regimen, with a GMT of around 450 IU L-1.
      High antibody levels were maintained at the end of one year. There was no
      statistically significant difference in the seroconversion rates and GMTs between
      the two regimens of vaccination. All subjects in group I seroconverted at 24
      weeks after one single dose of the vaccine. No adverse effects were reported
      except for complaints of some mild local and constitutional symptoms.
      CONCLUSIONS: The inactivated hepatitis A vaccine is highly immunogenic, safe and
      well-tolerated.

PMID- 8568487
TI  - Increased prevalence of atherosclerotic wall changes in patients with
      hyperlipidaemia after renal transplantation.
AB  - OBJECTIVES: The initial aim of this study was to evaluate the possibility of
      influencing atherosclerosis in hyperlipidaemic renal transplant patients by
      lowering blood lipids with gemfibrozil treatment. DESIGN: Although this double
      blind, randomized trial was stopped after 6 months owing to the suspicion of drug
      interference, we report here on the results of baseline ultrasonographic
      examinations. SETTING: The outpatient clinic at the Department of Transplantation
      Surgery, Huddinge University Hospital, Huddinge, Sweden. SUBJECTS AND METHODS:
      The carotid arteries were examined in 16 out of the 19 kidney transplant patients
      included in the study using an ultrasonographic duplex scanner. MAIN OUTCOME
      MEASURES: Plaque occurrence and the common carotid intima-media thickness of the
      renal transplant recipients were compared to the same parameters in a
      normotensive control group of approximately the same age from a previous study.
      RESULTS: An increased prevalence of plaque (75% of the patients having plaque on
      one or both sides) was seen in the hyperlipidaemic renal transplant patients in
      comparison with the control group (16%; P < 0.001). The common carotid intima
      media complex was thicker (P < 0.05), and the lumen diameter and the calculated
      cross-sectional intima-media area were greater (P < 0.01-0.001) in the transplant
      recipients. CONCLUSIONS: Markedly increased atherosclerotic wall changes are seen
      in the carotid arteries of patients with hyperlipidaemia after renal
      transplantation.

PMID- 8568489
TI  - A compound heterozygote for familial hypercholesterolaemia with a homozygous
      mother.
AB  - Homozygous familial hypercholesterolaemia (FH) is a rare disorder in which the
      patients develop severe hypercholesterolaemia and premature coronary
      atherosclerosis from childhood. Here we report a unique family with clustering of
      homozygous FH. The proband was a 25-year-old man, who showed marked
      hypercholesterolaemia, multiple xanthomas and severe coronary atherosclerosis.
      His mother also showed the typical characteristics of homozygous FH. Sequencing
      analysis of the low-density lipoprotein receptor gene revealed that he was a
      compound heterozygote, carrying two different point mutations. One was a novel
      mutation, FH Wakayama (Cys-->Ser at 317), derived from his mother, and the other
      was a recurrent mutation, FH Niigata (T-->C at 1845 + 2, 5' splice signal in
      intron 12), derived from his father. The proband we report seems to be a very
      rare case of an FH homozygote born from a homozygous mother.

PMID- 8568488
TI  - Tumour-induced hypoglycaemia in a patient with insulin-dependent diabetes
      mellitus.
AB  - We report on a case of malignant insulinoma occurring in a patient with genuine
      insulin-dependent diabetes mellitus (IDDM). A review of cases concerning patients
      with diabetes mellitus and insulinomas is presented, and reveals only patients
      with non-insulin-dependent diabetes mellitus (NIDDM). Our case appears to be the
      first in showing the combination of IDDM and a functioning malignant insulinoma.

PMID- 8568490
TI  - Transjugular intrahepatic portal-systemic shunt.

PMID- 8568491
TI  - Dietary protein restriction and the progression of chronic renal insufficiency: a
      review of the literature.
AB  - It is well known that dietary protein restriction can delay the appearance of
      uraemic symptoms and give symptomatic relief in patients with chronic renal
      failure. During the last decade, several investigators have argued that protein
      restriction instituted at an early phase in renal disease may influence the rate
      of progression of renal failure favourably. Animal experiments have given strong
      evidence that, in the case of nephron loss, high dietary protein promotes further
      loss of renal function. Many studies have been conducted to investigate the
      possible favourable effect of a protein-restricted diet in patients with renal
      disease. However, the scientific proof that long-term protein restriction delays
      the progression of chronic renal insufficiency in man is still missing.

PMID- 8568492
TI  - Concurrent conditional discrimination tests of transitive inference by macaque
      monkeys: list linking.
AB  - Processing of serial information was assessed by training six macaques on a five
      item list of objects arranged into the four conditional pairs, A-B+, B-C+, C-D+,
      and D-E+. An analogous list (F through J) was similarly trained. Subsequently,
      both lists were linked by training on E-F+, a pair that provided adjacent
      elements from each list. Then, all unique and trained object pairs from both
      lists were presented as a test. Results indicated that the objects were retained
      as a single, linearly organized list with choice accuracy directly related to
      interitem distance between paired objects. A second experiment explored the
      consequences of incidence of conflicting information on list organization. In
      both experiments, selections depended on representational processes and supported
      the view that monkeys and pigeons retain serial lists in qualitatively different
      ways.

PMID- 8568493
TI  - Recognition of aspect-dependent three-dimensional objects by an echolocating
      Atlantic bottlenose dolphin.
AB  - We examined the ability of a bottlenose dolphin (Tursiops truncatus) to recognize
      aspect-dependent objects using echolocation. An aspect-dependent object such as a
      cube produces acoustically different echoes at different angles relative to the
      echolocation signal. The dolphin recognized the objects even though the objects
      were free to rotate and sway. A linear discriminant analysis and nearest centroid
      classifier could classify the objects using average amplitude, center frequency,
      and bandwidth of object echoes. The results show that dolphins can use varying
      acoustic properties to recognize constant objects and suggest that aspect
      independent representations may be formed by combining information gleaned from
      multiple echoes.

PMID- 8568494
TI  - Dimensions of stimulus complexity.
AB  - Animal learning research has increasingly used complex stimuli that approximate
      natural objects, events, and locations, a trend that has accompanied a resurgence
      of interest in the role of cognitive factors in learning. Accounts of complex
      stimulus control have focused mainly on cognitive mechanisms and largely ignored
      the contribution of stimulus information to perception and memory for complex
      events. It is argued here that research on animal learning stands to benefit from
      a more detailed consideration of the stimulus and that James Gibson's stimulus
      centered theory of perception serves as a useful framework for analyses of
      complex stimuli. Several issues in the field of animal learning and cognition are
      considered from the Gibsonian perspective on stimuli, including the fundamental
      problem of defining the effective stimulus.

PMID- 8568495
TI  - Role of primary motivation in stimulus preexposure effects.
AB  - It is currently a matter of debate whether the deficit in conditioning observed
      after stimulus preexposure is one of acquisition or one of performance. The major
      criticism of performance-based theories is their inability to specify what is
      learned during nonreinforced preexposure that may influence subsequent
      acquisition of conditioned responding-Experiments 1 and 2 used an excitatory
      appetitive conditioning procedure and Experiment 3 used an inhibitory appetitive
      conditioning procedure, with rats as subjects, and consistently found that the
      effects of preexposure to a stimulus transferred to conditioning only when the
      reinforcer was relevant to the motivational state in which that preexposure was
      conducted. This finding suggests that during preexposure, rats learn that a
      stimulus is unrelated to events of relevance to their current motivational state.

PMID- 8568496
TI  - The what and the where of the pigeon's processing of complex visual stimuli.
AB  - Eight pigeons were trained on a go-no go visual discrimination involving 1 S+ and
      15 S- s. The 16 discriminative stimuli were black-and-white line drawings created
      by the factorial combination of 4 different geometric shapes (wedge, cylinder,
      cone, handle) in 4 different spatial locations (right, left, above, below) in
      relation to a common shape (cube). All of the pigeons readily learned this
      complex visual discrimination. Each bird's pecking behavior was controlled by
      both attributes of the line drawings, but somewhat stronger stimulus control was
      exerted by the location of the added component than by its shape. Across all 8
      pigeons, there was an inverse relation between stimulus control by component
      shape and component location. These results document pigeons' joint processing of
      "what" and "where" information in visual discrimination learning.

PMID- 8568497
TI  - Value transfer in a simultaneous discrimination appears to result from within
      event pavlovian conditioning.
AB  - When pigeons acquire a simple simultaneous discrimination, some of the value
      acquired by the S+ transfers to the S-. The mechanism underlying this transfer of
      value was examined in three experiments. In Experiment 1, pigeons trained on two
      simultaneous discriminations (A + B- and C +/- D-) showed a preference for B over
      D. This preference was reduced, however, following the devaluation of A. In
      Experiment 2, when after the same original training, value was given to D, the
      pigeons' preference for C did not significantly increase. In Experiment 3, when
      both discriminations involved partial reinforcement (S +/-), A + C- training
      resulted in a preference for B over D, whereas B + D- training resulted in a
      preference for A over C. Thus, simultaneous discrimination training appears to
      result in bidirectional within-event conditioning involving the S+ and S-.

PMID- 8568498
TI  - Quantity-based interference and symbolic representations in chimpanzees (Pan
      troglodytes).
AB  - Five chimpanzees with training in counting and numerical skills selected between
      2 arrays of different amounts of candy or 2 Arabic numerals. A reversed
      reinforcement contingency was in effect, in which the selected array was removed
      and the subject received the nonselected candies (or the number of candies
      represented by the nonselected Arabic numeral). Animals were unable to maximize
      reward by selecting the smaller array when candies were used as array elements.
      When Arabic numerals were substituted for the candy arrays, all animals showed an
      immediate shift to a more optimal response strategy of selecting the smaller
      numeral, thereby receiving the larger reward. Results suggest that a response
      disposition to the high-incentive candy stimuli introduced a powerful
      interference effect on performance, which was effectively overridden by the use
      of symbolic representations.

PMID- 8568499
TI  - Conditioned stimulus determinants of conditioned response form in Pavlovian fear
      conditioning.
AB  - Four experiments using barpress conditioned suppression in rats found that tone
      evoked more freezing (immobility) than did light. Still, tone and light appeared
      to have similar conditioned value as assessed by suppression in Experiments 1, 2,
      and 3, and by blocking, second-order conditioning, and overconditioning assays in
      Experiments 1, 2, and 3, respectively. Experiment 4 arranged for tone to evoke
      less suppression than light but more freezing. Results suggest that in fear
      conditioning, the nature of the conditioned stimulus affects the form of
      conditioned responding (strong vs. weak freezing). This conclusion extends one
      drawn by P. C. Holland (1977) on the basis of his work in appetitive
      conditioning.

PMID- 8568500
TI  - Age-dependent changes in thymuses in the European common frog, Rana temporaria.
AB  - The thymus of the adult frog Rana temporaria is generally small each winter and
      grows through the spring to reach a large size each summer. The summer thymus has
      a cortex full of small thymocytes and a medulla in the centre, whereas the winter
      atrophy is manifested by a loss of distinction between cortex and medulla, an
      abundance of cells filled with secretory granules, and the formation of
      intercellular cysts. These seasonal changes are superimposed on age changes. The
      thymus grows rapidly in froglets. The differences in weight and cell number
      between winter and summer organs are strongest in middle-aged animals (3-6 years
      old) and decrease in old specimens. The thymus slowly involutes with age, this
      being connected with increasing winter atrophy, leading to the formation of huge
      cysts that fill almost the whole organ in the oldest individuals. In senescent
      frogs (around 10 years old) seasonal differences still concern corticomedullary
      division but without pronounced fluctuations in thymic size. The
      skeletochronological technique applied here for age estimation underestimated
      rather than overestimated the real age of old animals.

PMID- 8568501
TI  - Sound production in Pituophis melanoleucus (Serpentes: Colubridae) with the first
      description of a vocal cord in snakes.
AB  - The pine, gopher, or bull snake (Pituophis melanoleucus) makes two different
      defensive sounds. Hisses are characterized by lack of frequency and amplitude
      modulation; bellows have a brief initial period of high-amplitude, broad
      frequency sound followed by a longer period of lower-amplitude, constant
      frequency sound. Both defensive sounds contain distinct harmonic elements. The
      modulation and harmonic nature of these sounds seems to be unique among snakes.
      The larynx of Pituophis is unusual in having an epiglottal keel, a dorsal
      expansion of the cricoid cartilage, previously proposed to contribute to sound
      production; however, this study shows that it plays only a small role in
      increasing the amplitude of bellows. Within the larynx of Pituophis is a "vocal
      cord," the laryngeal septum, which is a flexible, horizontal shelf of tissue that
      divides the anterior portion of the larynx. Removal of the laryngeal septum
      alters the defensive sounds and eliminates their harmonic elements. The laryngeal
      septum is unique among previously described vertebrate vocal cords or folds
      because it is supported by the cricoid (as opposed to arytenoid) cartilage and is
      a single (as opposed to bilaterally paired) structure.

PMID- 8568502
TI  - Development of electrical activity in regenerating aggregates of hydra cells.
AB  - The development of electrical activity in aggregates of dissociated hydra cells
      was investigated. Both the number of events and the distribution of amplitude of
      electrical pulses during the process of regeneration were determined.
      Correlations between electrical pulses at two separate positions on an aggregate
      were also examined as regeneration progressed. The main results were as follows:
      From the measured frequency and amplitude of pulses, together with the
      correlations between pulses at two different sites, we could observe the way in
      which contraction pulses developed in regenerating aggregates. The percentage of
      the electrical pulses of large amplitude increased about 20 hr after the start of
      regeneration. The correlation between electrical pulses measured at two sites
      separated by 0.3 mm also increased at about 20 hr, reaching about 80% at 40 hr.
      The results suggest the possible details of the reorganization of the conduction
      system for contraction pulses among cells in a regenerating aggregate of hydra
      cells.

PMID- 8568503
TI  - Who are we? We are only young once, make the best of it or get out of the way,
      here come the young'uns.

PMID- 8568504
TI  - South Florida Program on Aging and Health. Assessing the prevalence of
      Alzheimer's disease in three ethnic groups.
AB  - The South Florida Program on Aging and Health was initiated in 1992 with the aim
      to assess physical and mental health of the elderly in Dade County and provide a
      basis for public health policy. This report describes the methodology applied in
      the study and preliminary screening results in a probability sample of 2,400
      African American, Cuban American and white non-Hispanic American elderly men and
      women. Of 2,013 participants screened by May 1995, 11.5% had cognitive
      impairment. An increase in prevalence from 4-7% to 25-36% with advancing age was
      found among men and women of each group, from the youngest (65-74) to the oldest
      (85+ years). Male and female prevalences were similar but vary by ethnic group
      and age.

PMID- 8568505
TI  - Advance directives. Population prevalence and demand in Florida.
AB  - The level of knowledge is examined about the prevalence of and potential demand
      for advance directives--living wills and health-care surrogates--by adult
      residents of the state of Florida. Questions about advance directives were
      included in random digit dialing telephone surveys of 1,000 Florida residents 18
      years of age and older in November 1994 and April 1995. Surveys were completed by
      52% of the November sample and 56% of the April sample. Among those responding
      88% had heard of living wills and 25% of health-care surrogates; 25% had
      completed a living will and 8% had designated a health-care surrogate. Of those
      with no advance directives 73% said they would complete them if the forms were
      made readily available in convenient locations. Although a relatively high
      proportion of Florida residents have advance directives, there are independent
      age and socioeconomic effects in the likelihood of their completion. Advance
      directives are desired by many more people, but the current methods of educating
      and availing persons of the appropriate forms are not adequate to meet the
      demand.

PMID- 8568506
TI  - Camping with a friend. Helping adolescents cope with diabetes.
AB  - The Florida Camp for Children and Youth With Diabetes sponsored a weekend in
      which teenagers with diabetes invited a friend of the same sex without diabetes
      to participate in a two-day retreat. This program was designed to encourage
      friends to take an active role in motivating the teen with diabetes to perform
      his or her diabetes-related tasks in a responsible manner. Forty-six patients
      ranging in age from 12-17 years brought friends. Those with diabetes participated
      in rap sessions as well as educational sessions attempting to teach independence
      in self-care. The friends were taught the basics of diabetes as well as given an
      opportunity to inject saline and monitor their own blood glucose levels. A choice
      of activities was interspersed with education.

PMID- 8568507
TI  - Vertical transmission of HIV-1 infection. Diagnosis and prevention.
AB  - With an increase in the number of women of childbearing age being infected with
      HIV-1, the incidence of pediatric AIDS is rising precipitously. Therefore, it is
      necessary to identify the risks and the potential preventive methods that may be
      effective in decreasing the transmission from mother to child, i.e., vertical
      transmission. Administration of zidovudine has been demonstrated to significantly
      lower the rate of vertical transmission. Passive and active vaccination may also
      be useful in diminishing the transmission rate. Likewise, methods which provide a
      rapid and predictive measurement of the likelihood of vertical transmission, such
      as qualitative and quantitative differences in anti-HIV-1 maternal antibodies
      between transmitters and nontransmitters, have potential clinical utility.

PMID- 8568508
TI  - Administrative discipline.

PMID- 8568509
TI  - Medical ethics in managed care.

PMID- 8568510
TI  - Pharmacological analysis of heartbeat in Drosophila.
AB  - Analysis of the mechanisms underlying cardiac excitability can be facilitated
      greatly by mutations that disrupt ion channels and receptors involved in this
      excitability. With an extensive repertoire of such mutations, Drosophila provides
      the best available genetic model for these studies. However, the use of
      Drosophila for this purpose has been severely handicapped by lack of a suitable
      preparation of heart and a complete lack of knowledge about the ionic currents
      that underlie its excitability. We describe a simple preparation to measure
      heartbeat in Drosophila. This preparation was used to ask if heartbeat in
      Drosophila is myogenic in origin, and to determine the types of ion channels
      involved in influencing the heart rate. Tetrodotoxin, even at a high
      concentration of 40 microM, did not affect heart rate, indicating that heartbeat
      may be myogenic in origin and that it may not be determined by Na+ channels.
      Heart rate was affected by PN200-110, verapamil, and diltiazem, which block
      vertebrate L-type Ca2+ channels. Thus, L-type channels, which contribute to the
      prolonged plateau of action potentials in vertebrate heart, may play a role in
      Drosophila cardiac excitability. It also suggests that Drosophila heart is
      subject to a similar intervention by organic Ca2+ channel blockers as the
      vertebrate heart. A role for K+ currents in the function of Drosophila heart was
      suggested by an effect of tetraethylammonium, which blocks all the four
      identified K+ currents in the larval body wall muscles, and quinidine, which
      blocks the delayed rectifier K+ current in these muscles. The preparation
      described here also provides an extremely simple method for identifying mutations
      that affect heart rate. Such mutations and pharmacological agents will be very
      useful for analyzing molecular components of cardiac excitability in Drosophila.

PMID- 8568511
TI  - Projection pattern of sensory neurons in the central nervous system of a homeotic
      mutation of the moth Manduca sexta.
AB  - Octopod (Octo) is a mutation of the moth Manduca sexta, which transforms the
      first abdominal segment (A1) in the anterior direction. Mutant animals are
      characterized by the appearance of homeotic thoracic-like legs on A1. We
      exploited this mutation to determine what rules might be used in specifying the
      fates of sensory neurons located on the body surface of larval Manduca.
      Mechanical stimulation of homeotic leg sensilla did not cause reflexive movements
      of the homeotic legs, but elicited responses similar to those observed following
      stimulation of ventral A1 body wall hairs. Intracellular recordings demonstrated
      that several of the motoneurons in the A1 ganglion received inputs from the
      homeotic sensory hairs. The responses of these motoneurons to stimulation of
      homeotic sensilla resembled their responses to stimulation of ventral body wall
      sensilla. Cobalt fills revealed that the mutation transformed the segmental
      projection pattern of only the sensory neurons located on the ventral surface of
      A1, resulting in a greater number with intersegmental projection patterns typical
      of sensory neurons found on the thoracic body wall. Many of the sensory neurons
      on the homeotic legs had intersegmental projection patterns typical of abdominal
      sensory neurons: an anteriorly directed projection terminating in the third
      thoracic ganglion (T3). Once this projection reached T3, however, it mimicked the
      projections of the thoracic leg sensory neurons. These results demonstrate that
      the same rules are not used in the establishment of the intersegmental and leg
      specific projection patterns. Segmental identity influences the intersegmental
      projection pattern of the sensory neurons of Manduca, whereas the leg-specific
      projections are consistent with a role for positional information in determining
      their pattern.

PMID- 8568512
TI  - Identification of the border between fibronectin type III homologous repeats 2
      and 3 of the neural cell adhesion molecule L1 as a neurite outgrowth promoting
      and signal transducing domain.
AB  - To determine the domains of the neural cell adhesion molecule L1 involved in
      neurite outgrowth, we have generated monoclonal antibodies against L1 and
      investigated their effects on neurite outgrowth of small cerebellar neurons in
      culture. When the 10 antibodies were coated as substrate, only antibody 557.B6,
      which recognizes an epitope represented by a synthetic peptide comprising amino
      acids 818 to 832 at the border between the fibronectin type III homologous
      repeats 2 and 3, was as efficacious as L1 in promoting neurite outgrowth,
      increasing intracellular levels of Ca2+, and stimulating the turnover of inositol
      phosphates. These findings suggest that neurite outgrowth and changes in these
      second messengers are correlated. Such a correlation was confirmed by the ability
      of Ca2+ channel antagonists and pertussis toxin to inhibit neurite outgrowth on
      L1 and antibody 557.B6. These observations indicate for the first time a distinct
      site on cell surface-bound L1 as a prominent signal-transducing domain through
      which the recognition events appear to be funneled to trigger neurite outgrowth,
      increase turnover of inositol phosphates, and elevate intracellular levels of
      Ca2+.

PMID- 8568513
TI  - Establishment of neuronal connectivity during development of the Drosophila
      larval visual system.
AB  - We used confocal microscopy in conjunction with specific antibodies and enhancer
      trap strains to investigate the development of specific neuronal connections in a
      simple model system, the larval visual system of Drosophila. We find that the
      establishment of axonal projections from the larval photoreceptor neurons to
      their central nervous system targets involves a series of discrete steps. During
      embryogenesis, the larval optic nerve contacts several different cell types,
      including optic lobe pioneer (OLP) neurons and a number of glial cells. We
      demonstrate that OLP neurons are present and project normally in glass (gl)
      mutant embryos in which the larval optic nerve fails to develop, suggesting that
      they do not depend on interactions with the larval optic nerve for
      differentiation and proper axonal projection. The OLPs fail to differentiate
      properly is disconnected (disco) mutant embryos, where appropriate connections
      between the larval optic nerve and its targets in the brain are not formed. The
      disco gene is expressed in the OLPs and may therefore act autonomously to direct
      the differentiation of these cells. Taken together, our results suggest that the
      OLPs act as an intermediate target required for the establishment of normal optic
      nerve projection and connectivity.

PMID- 8568515
TI  - Importance of target innervation in recovery from axotomy-induced loss of
      androgen receptor in rat perineal motoneurons.
AB  - In adult male rats, axotomy of the spinal nucleus of the bulbocavernosus (SNB)
      motoneurons transiently down-regulates androgen receptor (AR) immunoreactivity.
      The present study investigates the importance of target reinnervation in the
      recovery of AR expression in axotomized SNB motoneurons after short (up to 5
      days) and long (1 to 6 weeks) periods of recovery. In the long-term recovery
      experiment, animals were divided into two groups. In one, the two stumps of the
      cut pudendal nerve, which carries the axons of the SNB motoneurons, were sutured
      together immediately after axotomy. In the second group, the proximal stump was
      ligated immediately after axotomy to prevent target reinnervation. Axotomy of the
      SNB motoneurons caused a significant down-regulation in AR immunoreactivity
      within 3 days. At 6 weeks, AR immunoreactivity was still depressed in ligated
      animals but had recovered to control levels in resutured animals. The recovery in
      the resutured group was coincident with the first signs of reinnervation of the
      target perineal muscles, although reinnervation seemed to lag behind AR
      immunoreactivity. SNB soma size was significantly reduced 2 weeks after axotomy
      and returned to control levels after 6 weeks of recovery only in the resutured
      animals. These findings suggest that the target perineal muscles play a role in
      the regulation of AR expression and androgen sensitivity in the SNB motoneurons,
      perhaps mediated by muscle-derived trophic factors.

PMID- 8568514
TI  - Neurotrophin-4/5, brain-derived neurotrophic factor, and neurotrophin-3 promote
      survival of cultured vestibular ganglion neurons and protect them against
      neurotoxicity of ototoxins.
AB  - The ability of neurotrophin-4/5 (NT-4/5), brain-derived neurotrophic factor
      (BDNF), neurotrophin-3 (NT-3), and nerve growth factor (NGF) to promote survival
      of postnatal rat vestibular ganglion neurons (VGNs) was examined in dissociated
      cell cultures. Of the four neurotrophins, NT-4/5 and BDNF were equally effective
      but more potent than NT-3 in promoting the survival of VGNs. In contrast, NGF
      showed no detectable effects. As expected, TrkB-IgG (a fusion protein of
      extracellular domain of TrkB and Fc domain of human immunoglobulin G)
      specifically inhibited the survival-promoting, effects by NT-4/5 or BDNF and TrkC
      IgG fusion protein completely blocked that of NT-3. Immunohistochemistry with
      TrkB, TrkA, and p75 antisera revealed that VGNs made TrkB and p75 proteins, but
      not TrkA protein. Ototoxic therapeutic drugs such as cisplatin and gentamicin
      often induce degeneration of hair cells and ganglion neurons in both auditory and
      vestibular systems that leads to impairment of hearing and balance. When
      cisplatin and gentamicin were added to the dissociated VGN culture in which the
      hair cells were absent, additional cell death of VGNs was induced, suggesting
      that the two ototoxins may have a direct neurotoxic effect on ganglion neurons in
      addition to their known toxicity on hair cells. However, if the cultures were co
      treated with neurotrophins, NT-4/5, BDNF, and NT-3, but not NGF, prevented or
      reduced the neurotoxicity of the two ototoxins. Thus, the three neurotrophins are
      survival factors for VGNs and are implicated in the therapeutic prevention of VGN
      loss caused by injury and ototoxins.

PMID- 8568516
TI  - Ciliary neurotrophic factor arrests muscle and motoneuron degeneration in
      androgen-insensitive rats.
AB  - Steroid hormones and neurotrophic factors exert profound and widespread effects
      on the developing nervous system, including regulation of the size, connectivity,
      and survival of neurons. Androgenic control of the survival of motoneurons in the
      spinal nucleus of the bulbocavernosus (SNB) of rats has been well documented. We
      previously found that ciliary neurotrophic factor (CNTF) mimics many effects of
      androgen on the developing SNB. Whether effects of CNTF depend on the presence of
      a functional androgen receptor was evaluated in the present study. Androgen
      insensitive male rats bearing the testicular feminization mutation, Tfm, and
      female litter-mates were treated with CNTF or with vehicle alone from embryonic
      day 22 through postnatal day 3. On postnatal day 4 SNB cell number was elevated
      in both groups receiving CNTF. Volumes of the bulbocavernosus (BC) and levator
      ani (LA) muscles, targets of SNB motoneurons, were also markedly increased by
      CNTF. Since the BC appears to degenerate completely in untreated females, these
      results indicate that CNTF can delay or prevent muscle fiber death. The relative
      sparing of muscles and motoneurons did not differ for Tfm males and females,
      demonstrating that effects of CNTF on the SNB neuromuscular system do not require
      functional androgen receptors.

PMID- 8568517
TI  - Conditions for the primary culture of eye imaginal discs from Drosophila
      melanogaster.
AB  - We have established a primary culture system for Drosophila eye imaginal discs.
      With this system, we were able to obtain neurite outgrowth from intact eye discs,
      eye disc fragments, and dissociated eye imaginal disc cells. Immunoreactivity to
      antibody 24B10 indicates that these extending neurites are photoreceptor axons.
      Three culture media were tested for their ability to support the survival of and
      neurite extension from eye disc fragments in vitro at 23 degrees C. These, with
      supplements, were: five parts of Schneider's Drosophila medium with four parts of
      basal Eagle's medium ("4 + 5"); Leibovitz's L-15 medium (L-15); and Shields and
      Sang's M3 modified medium (MM3). We obtained the best results with MM3
      supplemented with 2% fetal bovine serum (FBS). Eye disc fragments survived in
      this medium for at least 20 days. Pigmentation in the nonphotoreceptor pigment
      cells in cultures from the prepupa required the presence of 20-hydroxyecdysone
      (20-HE) (1 micrograms/ml), whereas neurite outgrowth was seen in the absence of
      20-HE. Donor animals had to fall within a range of ages to obtain appropriate eye
      disc differentiation in vitro. Eye disc from 5-h pupae (P + 5) or older commenced
      ommachrome synthesis in vitro in a temporal sequence close to that found in vivo,
      whereas the in vitro synthesis of this pigment was delayed in eye discs from
      younger flies. Average neurite length was not affected by age among pupae younger
      than P + 5; but neurite outgrowth from P + 24 was scarce, probably because by
      this time photoreceptor axons had already grown in vivo and were severed and
      unable to regenerate in vitro. Eye discs taken from third instar larvae or white
      prepupae continued their mitotic activity in vitro. Together with the advance of
      the morphogenetic furrow at the leading edge of retinal development, this
      observation is consistent with the evidence that pattern formation continues in
      vitro. Morphogenetic changes were manifested in cultures. Viability tests with
      calcein AM and ethidium bromide revealed few dead cells in living cultures.

PMID- 8568518
TI  - Distinct adhesive properties of ciliary and choroid neurons from the avian
      ciliary ganglion.
AB  - The avian ciliary ganglion (CG) contains two populations of neurons: ciliary
      neurons, which innervate striated muscle, and choroid neurons, which innervate
      vascular smooth muscle. We used cell size (ciliary cells are larger) and
      somatostatin immunoreactivity (which is restricted to choroid cells) as markers
      to compare the adhesive properties of these two neuronal types. Similar numbers
      of freshly dissociated embryonic chick ciliary and choroid neurons adhered to
      laminin (laminin 1) and polylysine, consistent with the fact that each population
      comprises about half of the ganglionic neurons. In contrast, severalfold more
      ciliary neurons than choroid neurons adhered to a recombinant fragment of a
      synapsespecific basal lamina protein, s-laminin/laminin beta 2. Moreover,
      severalfold more ciliary neurons than choroid neurons adhered to a plastic
      surface when assayed by the method of Needels et al. in serum-free medium.
      Adhesion to s-laminin and plastic appears to be mediated by different cell
      surface components, as adhesion to recombinant s-laminin is inhibited by the
      tripeptide, LRE, and by Ca2+ ions, but not by heparin, whereas adhesion to
      plastic is LRE and Ca2+ insensitive but heparin sensitive. Both adhesive
      differences are apparent at embryonic day 8, soon after the ciliary and choroid
      neurons have begun to form synapses. Thus, two sets of neurons in the CG that
      send axons through different nerves and innervate different targets also show
      distinct adhesive behaviors.

PMID- 8568519
TI  - Tenascin-C mRNA is expressed in cranial neural crest cells, in some placodal
      derivatives, and in discrete domains of the embryonic zebrafish brain.
AB  - A partial zebrafish tenascin-C cDNA clone was isolated from an embryonic
      zebrafish cDNA library on the basis of homology to mouse tenascin-C. The
      expression pattern in the head of embryonic zebrafish was analyzed by in situ
      hybridization. Tenascin-C mRNA was detected in neural crest cells during the
      period of their migration and differentiation. Expression also occurred in
      differentiating placodal tissues and in mesodermal cells. In the developing
      brain, tenascin-C mRNA was expressed in specific domains. In the hindbrain the
      pattern of the domains was dynamic. At 18 to 22 h postfertilization, expression
      was widespread in rhombomeres 3, 5, and 6, confined to periventricular cells in
      rhombomere 2, and not detectable in rhombomere 4. At 32 h postfertilization,
      tenascin-C was expressed at the rhombomere boundaries. In contrast to the
      hindbrain, the pattern in the forebrain and midbrain did not show any major
      changes between 22 and 32 h postfertilization. Domains expressing tenascin-C
      alternated with regions devoid of it. The most anterior domain of expression was
      observed at the telencephalic-diencephalic border, surrounding the optic recess.
      A second domain, at the border between the diencephalon and the midbrain, and a
      third domain, in the caudal midbrain tegmentum, appeared restricted to the basal
      plate. Additionally, expression of tenascin-C mRNA was detected in the
      hypothalamus and in the developing epiphysis. These expression patterns suggest
      that tenascin-C may play a role in neural crest cell migration and during the
      differentiation of neural crest, placodal, and mesodermal derivatives. In the
      developing brain, tenascin-C may be involved in the consolidation of different
      regional identities.

PMID- 8568520
TI  - Unilateral spatial neglect due to a haemorrhagic contusion in the right frontal
      lobe.
AB  - We report two cases of unilateral spatial neglect associated with an isolated
      right frontal lobe lesion. Case 1 was a 59-year-old, right-handed man, who
      developed a left hemiplegia, disorientation, and frontal lobe neglect associated
      with a haemorrhagic contusion following a head injury. Case 2 was a 55-year-old,
      right-handed man, who also developed disorientation and frontal lobe neglect
      secondary to a haemorrhagic contusion following a head injury. 99mTc HM-PAO SPECT
      revealed an isolated reduction in the regional cerebral blood flow (CBF) around
      the haematoma in the frontal lobe; blood flow to remaining parts of the brain was
      normal. Damage to the right frontal lobes of these patients was confirmed as
      being the cause of the unilateral spatial neglect in accordance with the results
      of CBF studies.

PMID- 8568521
TI  - Stiff-person syndrome with anti-glutamic acid decarboxylase autoantibodies:
      complete remission of symptoms after intrathecal baclofen administration.
AB  - A female patient, aged 61 years, who developed a severe immobilizing stiff-person
      syndrome in conjunction with insulin-dependent diabetes mellitus, is described.
      In addition to the typical clinical symptoms, diagnosis was proven by the
      presence of autoantibodies against glutamic acid decarboxylase in serum and
      cerebrospinal fluid. Symptomatic treatment with continuous intrathecal
      application of baclofen administered by a subcutaneous pump resulted in rapid
      clinical improvement so that the patient became ambulatory. Intermittent
      withdrawal from intrathecal baclofen therapy led to complete remanifestation of
      stiff-person syndrome within 18 h; after re-introduction of intrathecal therapy
      stiffness disappeared completely within 48 h. The clinical course has been stable
      now for over 24 months and stiffness has completely disappeared. The effect of
      baclofen in this patient is discussed in the light of the suggested
      pathophysiological mechanisms in stiff-person syndromes.

PMID- 8568522
TI  - Clinico-pathophysiological features of acute autonomic and sensory neuropathy: a
      long-term follow-up study.
AB  - We evaluated the clinico-pathophysiological features of three patients with acute
      autonomic and sensory neuropathy (AASN) who were followed for over 3 years. Signs
      of an autonomic disturbance including vomiting, anhidrosis, urinary disturbances,
      orthostatic hypotension and reduced coefficient of variation of the R-R interval
      on electrocardiography gradually improved about 1 year after onset. However, all
      three exhibited severe generalized sensory impairment for all modalities with the
      development of persistent sensory ataxia. No sensory nerve action potentials
      could be elicited and no somatosensory evoked potentials could be obtained. Sural
      nerve biopsy revealed severe axonopathy. In two patients, a high-intensity area
      was observed in the posterior column of the spinal cord on T2*-weighted axial
      magnetic resonance images. The level of neuron-specific enolase in cerebrospinal
      fluid was markedly elevated in two patients, indicating spinal nerve root or
      sensory neuron damage. Motor nerve function was well preserved in all patients.
      Our findings suggests that the major lesion in patients with AASN, particularly
      those with a sensory deficit, is present in the dorsal root ganglion neurons,
      that is there is a ganglioneuronopathy.

PMID- 8568523
TI  - An epidemic of optic neuropathy and painful sensory neuropathy in Cuba: clinical
      aspects.
AB  - An epidemic of bilateral optic neuropathy and painful sensory neuropathy occurred
      in Cuba in 1991-1993. Over 45,000 individuals were stated to have been affected.
      We report a clinical study on 25 patients seen in Cuba in 1993-1994. Affected
      patients showed either bilateral optic neuropathy with caecocentral scotomata or
      a distal predominantly sensory neuropathy sometimes associated with deafness, or
      a combination of both optic and peripheral sensory neuropathy. The nature of the
      epidemic is discussed. The clinical features in patients with confirmed
      neurological deficits were consistent with a diagnosis of Strachan's syndrome,
      probably related to nutritional deficiency. Other patients with similar symptoms
      showed no evidence either of optic or peripheral neuropathy and were considered
      to represent disease mimicry on a psychoneurotic basis.

PMID- 8568524
TI  - Cardiac autonomic function during sleep and wakefulness in multiple sclerosis.
AB  - Some studies in multiple sclerosis (MS) patients have shown evidence of autonomic
      dysfunction involving the cardiovascular system. However, the findings in these
      studies have not been completely consistent. The discrepancy may be related to
      the limits of the traditional autonomic tests during wakefulness. In our study,
      after the investigation of the cardiovascular reflexes during wakefulness, heart
      rate (HR) variations were considered during sleep in order to avoid the limits of
      cooperation and the emotional state of the patient. We evaluated tonic (vagal
      activity) HR modifications in relation to the deepening of sleep, as well as
      phasic (sympathetic activity) HR modifications in relation to spontaneous body
      movements during sleep, in 25 MS patients and 25 age-matched controls. No
      difference was found between the two groups in autonomic function during
      wakefulness. A reduced parasympathetic activity was observed in MS subjects
      during both rapid eye movement (REM) and non-REM sleep, while no difference was
      found in sympathetic function between patients and controls. No significant
      correlation was found between cardiac autonomic data during sleep and MRI lesion
      load in the infratentorial areas and, in particular, of the brain stem. The
      findings of our study suggest that autonomic nervous system evaluation during
      sleep could show impairment earlier than the traditional autonomic tests during
      wakefulness.

PMID- 8568526
TI  - The Functional Limitations Profile may be a valid, reliable and sensitive measure
      of disability in multiple sclerosis.
AB  - This pilot study was designed to evaluate the usefulness of the Functional
      Limitations Profile (FLP), a validated interval measure of self-report of
      disability, in studies of multiple sclerosis (MS). It is compared with the
      standard measure of disability in MS, the Kurtzke Expanded Disability Status
      Scale (EDSS), and the Illness Severity Score (ISS), which is an interval score
      derived from the EDSS. Inherent problems of all measures are discussed. On two
      occasions separated by 6 months, 50 MS patients were assessed prospectively by a
      neurologist and a psychologist, using the above measures. Validity was reflected
      in correlation and in agreement between measures. The FLP Physical dimension
      correlated significantly with the EDSS for both visits (at visit 1: r = 0.77; at
      visit 2: r = 0.77). Agreement between the interval measures, FLP and ISS, was
      satisfactory (mean difference +0.18, SD 6.8). The reliability of FLP was assessed
      by comparing FLP Physical dimension scores in the 30 patients who had not changed
      clinically between visits (EDSS change < 1.0, ISS change < 3.8). For this
      unchanged group the mean difference was +0.56 (SD 6.2); the 95% confidence
      interval (CI) was -2.87 to +1.75. For sensitivity of the FLP the 20 MS patients
      who had clinically changed between visits were assessed (EDSS =/> 1.0, ISS =/>
      3.8). For this changed group the mean difference was -8.0 (SD 9.21); 95% CI was 
      12.3 to -3.69. The FLP Physical dimension in this pilot study seems to be a
      valid, reliable and sensitive measure of MS disability. If confirmed by larger
      studies it would be useful in prospective clinical studies of treatments for MS.

PMID- 8568525
TI  - Limited value of cerebrospinal fluid for direct detection of Toxoplasma gondii in
      toxoplasmic encephalitis associated with AIDS.
AB  - The diagnosis of acquired immunodeficiency syndrome-associated toxoplasmic
      encephalitis (TE), a typically focal disease resulting from reactivation of
      tissue cysts, relies mainly on indirect diagnostic methods. In a prospective
      study, we investigated the value of detection of Toxoplasma gondii in
      cerebrospinal fluid (CSF) by using the polymerase chain reaction and the mouse
      inoculation test. Twenty-four patients with 26 episodes of TE, 2 HIV-infected
      patients with primary acute Toxoplasma infection, and 38 HIV-infected control
      patients with latent Toxoplasma infection were investigated. Detection of T.
      gondii in CSF by both methods was possible in only 3 of the TE patients (11.5%),
      the remaining patients being negative with either of the methods. In contrast, T.
      gondii DNA was detected in both of the acutely infected patients, indicating that
      in primary acute toxoplasmosis parasites may easily be found in the CSF, whereas
      in the majority of TE cases in immunocompromised patients, T. gondii parasites do
      not gain access to the CSF drawn by lumbar puncture.

PMID- 8568527
TI  - Lyme borreliosis and cranial neuropathy.
AB  - In a 2-year study of 37 consecutive adult patients with isolated cranial nerve
      affection of primarily unknown origin, seen at a neurological clinic, borrelia
      infection was identified as the cause in six cases. Four patients had a
      peripheral facial palsy and two had a sixth nerve palsy. The patients with
      borreliosis had headaches or other pain considerably more often than patients
      with other or unknown aetiology. All six patients had accompanying symptoms
      and/or signs; in five cases these were obvious, and pointed to a borrelia
      infection. This study indicates that a careful history to elicit other symptoms
      of Lyme borreliosis will usually identify the cranial nerve affections with
      borrelial aetiology in adult patients. To verify the diagnosis, both serum and
      CSF analysis should be performed. Routine testing for borrelia serology in all
      patients with cranial neuropathy is generally not indicated.

PMID- 8568528
TI  - Haplotype analysis of French, British and other European patients with familial
      amyloid polyneuropathy (met 30 and tyr 77).
AB  - Familial amyloid polyneuropathy (FAP) is an autosomal dominant disorder
      originally and most frequently described in Portugal. The usual constituent
      amyloid fibril protein is transthyretin (TTR) and the most frequent mutation in
      the TTR gene associated with FAP (including all Portuguese cases) is that at
      position 30 (met 30). Three different TTR haplotypes have been described in
      association with the met 30 mutation in European patients. We studied the
      haplotypes of 27 families (24 French, 2 British and 1 Greek) with FAP met 30 by
      analysing three polymorphisms in introns of the TTR gene. We also studied 6
      families (2 British, 3 French and 1 Spanish) with FAP tyr 77. There were two main
      haplotypes in French patients with FAP met 30, one most commonly seen in the
      French families of Portuguese descent which was the same haplotype as previously
      described in Portuguese patients (haplotype I) and another haplotype (III)
      detected in most informative French families not of Portuguese origin. The age of
      onset of symptoms was consistently later in French than in Portuguese patients
      and in patients with haplotype III as the disease-associated haplotype rather
      than haplotype I. British and French patients with the tyr 77 mutation had
      different haplotypes. The most likely explanation of these findings is multiple
      founders of both mutations.

PMID- 8568529
TI  - Somatosensory evoked potentials in acute neurological decompression illness.
AB  - Somatosensory evoked potentials (SSEPs) were recorded on posterior tibial nerve
      stimulation during compression in 21 episodes of acute neurological decompression
      illness (DCI) involving 20 patients. A further two cases were monitored
      immediately after treatment only. The results were compared with previously
      published normal data from this laboratory and with recordings obtained during
      the compression of four normal volunteers. Compression had no effect on SSEPs in
      normal subjects: SSEP latency abnormalities were found in 17 of the episodes of
      DCI. An SSEP improvement at final recording was noted in 7 of the 11 episodes
      which were monitored during treatment and classified initially as
      neurophysiologically abnormal. SSEPs may assist in the diagnosis of DCI.

PMID- 8568530
TI  - Susceptibility to multiple sclerosis and the immunoglobulin heavy chain variable
      region.
AB  - A haplotype marker consisting of three biallelic restriction fragment length
      polymorphism (RFLP) loci from the VH-2 variable gene family was examined in 124
      families with sibling pairs concordant for multiple sclerosis, 178 unrelated
      patients and 159 unaffected controls to investigate the role of the
      immunoglobulin heavy chain gene cluster in susceptibility to multiple sclerosis.
      Evidence for linkage was assessed using the affected sibling pair method of
      identity by descent, modified to allow for haplotype sharing on a probabilistic
      basis in families where haplotypes could not be assigned with certainty. The
      estimated probabilities of affected siblings sharing 0, 1 or 2 haplotypes were Z0
      = 0.20, Z1 = 0.45, Z2 = 0.35. This deviation from the expected sharing
      probabilities of Z0 = 0.25, Z1 = 0.5, Z2 = 0.25 provides evidence for weak
      linkage (P < 0.05; equivalent to a lod score of 0.84); however, no significant
      allelic or haplotypic association was observed. Linkage without a population
      association suggests that a gene encoded on 14q confers susceptibility to
      multiple sclerosis, although this is not any of the existing VH-2 polymorphisms.

PMID- 8568531
TI  - Distribution of epidermal growth factor receptor gene amplification in brain
      tumours and correlation to prognosis.
AB  - In 75 gliomas and 31 meningiomas, mutations at the epidermal growth factor
      receptor (EGFR) gene locus were restricted to gliomas. The ligands of this
      receptor, epidermal growth factor and transforming growth factor alpha, lacked
      quantitative changes at their loci in gliomas and meningiomas. EGFR gene
      amplification occurred in astrocytomas, oligodendrogliomas, ependymomas and
      glioblastomas. The frequency of this mutation significantly increased with the
      malignancy grade and the patient's age. Especially in glioblastomas of
      individuals aged over 64 years, EGFR gene mutations were observed without
      chromosome-10-specific allele losses. This finding contradicts the hypothesis
      that deletion of one entire chromosome 10 regularly precedes EGFR gene
      amplification in primary glioblastomas of patients aged over 50 years. It was
      found that most individuals whose gliomas carry an EGFR gene mutation have a poor
      prognosis, comparable to that of glioblastoma patients even when the tumour is
      graded as benign.

PMID- 8568533
TI  - Percutaneous endoscopic gastrostomy and enteral nutrition in amyotrophic lateral
      sclerosis.
AB  - Bulbar involvement in amyotrophic lateral sclerosis (ALS) is often related to a
      worse prognosis on account of the higher risk of pulmonary aspiration and
      undernutrition due to dysphagia. The aim of our study was to assess the effects
      of enteral feeding by percutaneous endoscopic gastrostomy (PEG) in a long-term
      follow-up of ALS patients. We report the results of PEG in 31 ALS patients with
      bulbar involvement. The patients were observed at 3-monthly intervals over a
      period of 2 years after PEG. All the data were compared with those obtained from
      a control group of 35 ALS patients who refused PEG. Mortality did not differ
      significantly between the two groups of patients during the first 6 months of
      observation, whereas after this period it was lower in the PEG group. In the
      patients who had had PEG, the body mass index showed a mild but statistically
      significant improvement after tube insertion while in the control group it
      decreased significantly. The findings of this study demonstrate that PEG can
      improve survival in elderly and young ALS patients with bulbar involvement; it
      enhances their quality of life and helps their integration in their social and
      family surroundings. We think that PEG should be included symptomatic treatment
      of all ALS patients with bulbar involvement from the onset of symptoms.

PMID- 8568532
TI  - Cardiac myxomas: a long term study.
AB  - From 1980 to 1992 we followed 12 patients with cardiac myxomas for an average of
      4.4 years (8 months-11 years). Presenting symptoms were neurological in four
      patients (hemiparesis, aphasia, visual field deficits, progressive dementia or
      vertigo), progressive dyspnoea in six, pulmonary embolism in one, and peripheral
      arterial or renal emboli in three. The diagnosis was suspected clinically in 11
      patients. It was confirmed by echocardiography in ten and by thoracic CT in one.
      All these patients had cardiac surgery. One diagnosis was made at autopsy; the
      patient died unexpectedly during surgery for emboli to the leg arteries. At
      follow-up, two additional patients had died, one from myocardial infarction and
      one from rhabdomyosarcoma. Only one of the nine surviving patients had recurrent
      symptoms after cardiac surgery. His dementia continued to progress. The patients
      without new symptoms after cardiac surgery had normal MRI of the brain or
      residual ischaemic lesions. MRI of the patient with progressive dementia showed
      multiple cerebral lesions with a bright centre and a dark rim on T1- and T2
      weighted spin-echo images. On CT there were many calcified lesions. CT, MR
      angiography and contrast angiography revealed multiple fusiform aneurysms. The
      rare occurrence of progressive neurological symptoms after myxoma resection with
      multiple cerebral lesions and aneurysms should suggest myxoma metastases to the
      brain.

PMID- 8568534
TI  - Correlation of quantitative measures with the modified Ashworth scale in the
      assessment of plantar flexor spasticity in patients with traumatic brain injury.
AB  - This study of plantar flexor spasticity describes relationships among a
      traditional qualitative spasticity scale, three potential quantitative spasticity
      measures and a measure of voluntary ankle muscle function. Thirty-four volunteer
      adult patients with traumatic brain injuries participated. There were 28 males
      and 6 females; the mean age was 30.3 years. A battery of five randomly sequenced
      tests was performed for each subject on one ankle. Tests were: modified Ashworth
      scale (MAS) scoring; H-reflex testing with and without Achilles tendon vibration;
      H-reflex testing with and without dorsiflexor contraction; reflex threshold angle
      and timed toe tapping (TTT). Twenty-six subjects returned to have the second
      ankle tested, resulting in 60 ankles for the analyses. Spearman's coefficients
      for correlation of quantitative spasticity measures with MAS scores ranged from
      0.39 to 0.49 with associated probabilities < or = 0.002. Pearson coefficients for
      correlation of quantitative spasticity measures with TTT scores were lower but
      also significant (P < or = 0.07). Multiple correlation for the set of
      quantitative measures yielded R = 0.614 (P < 0.001) with MAS scores and R = 0.365
      (P = 0.045) with TTT scores. These findings reveal statistically significant
      relationships of low to moderate strength among potential quantitative spasticity
      measures, a traditional qualitative spasticity scale and a simple measure of
      voluntary ankle muscle function. Understanding these relationships is an
      essential part of the ongoing search for quantitative spasticity measures.

PMID- 8568535
TI  - Loss of alleles in brain tumours: distribution and correlations with clinical
      course.
AB  - Gliomas (n = 44) and meningiomas (n = 24) of different grades of malignancy were
      analysed for allele losses at loci on chromosomes 10, 13, 17 and 22. Deletions of
      genetic material on these chromosomes occurred in gliomas without being
      restricted to any histological entity. The frequency of chromosome-10-specific
      allele losses increased significantly with the age of the patients and with the
      grade of malignancy of the tumours. Deletions of chromosome 10 material were
      associated with a poor prognosis. The glioblastomas of patients aged over 70
      years lacked the loss of the entire chromosome 10, even in tumours with EGFR gene
      amplification. Deletions at loci of chromosomes 13, 17 and 22 were observed in 18
      32% of all gliomas, independent of grade of malignancy, patients' age, EGFR gene
      amplification and clinical course. Only chromosome-22-specific allele losses were
      found preferentially in gliomas of female patients. Loss of chromosome 22 alleles
      in 44% was the only mutation detected in meningiomas. This occurred independently
      of grade of malignancy and biological factors.

PMID- 8568536
TI  - Clonidine in the treatment of spasticity in patients with multiple sclerosis.

PMID- 8568537
TI  - An additional source of potentials recorded from the scalp following magnetic
      stimulation over the lower occiput and adjoining neck.

PMID- 8568538
TI  - Epidemiology of lower respiratory tract infections.
AB  - The aim of this review is to focus on the epidemiology of lower respiratory tract
      infections, the etiology, prognosis and risk factors, dividing these problems
      into the following issues: global impact of these afflictions, community-acquired
      pneumonia, hospital acquired pneumonia, respiratory infections in surgery, acute
      bronchitis and exacerbations of chronic bronchitis. Every year about 5 million
      people die of acute respiratory infections. Among these, pneumonia represents the
      most frequent cause of mortality, hospitalization and medical consultation.
      Several factors (age, underlying disease, environment) influence mortality,
      morbidity and also microbial etiology. The authors also refer to recent data on
      the most frequently identified antibiotic resistance of respiratory pathogens.
      The knowledge of such different clinico-epidemiological situations is essential
      to physicians for an effective approach to treatment of pneumonia and bronchitis.

PMID- 8568539
TI  - Etiology and risk factors of adult pneumonia.
AB  - The authors point out the remarkable importance that pneumonia has today among
      infectious diseases, and survey the main risk factors and etiological agents both
      of the forms acquired in the community and in the hospital, also considering the
      data from the international literature. The authors stress the high incidence of
      gram-positive microorganisms, among which Streptococcus pneumoniae is the most
      widespread in the forms acquired in the community, and the absolute prevalence of
      the gram-negatives in the nosocomial forms and, among the gram-positives, the pre
      eminence of Staphylococcus aureus; these are "difficult" bacterial species, whose
      prevalence has been determined mainly by induced selective pressure through the
      inadequate use of antibiotics. The authors also point out the principal factors
      that favor the onset of pneumonia; they are connected to the host and to the
      environment; their combination with the infectious agent causes the infective
      event.

PMID- 8568540
TI  - Evaluation of the invasive techniques for diagnosing bacterial respiratory
      infections.
AB  - Bacterial community-acquired respiratory infections are usually sustained by
      strains highly responsive to antibiotic therapy. Thus, the clinical approach is
      based on an empirical treatment and does not require the isolation of the
      causative pathogen and the determination of the bacterial susceptibility to
      antibiotics. On the other hand, Gram-negative bacteria, most commonly multidrug
      resistant, frequently affect immunocompromised and nosocomial patients and their
      identification in cultures is absolutely necessary for proper antibacterial
      treatment. To this aim, two conventional methods are used, i.e. the blood
      culture, which is positive only in 20% of pneumonia cases, and the sputum
      culture, which is not invasive but easily contaminated by oropharyngeal flora.
      Consequently, invasive techniques for sampling the pathologic specimen, such as
      the BAL and the PSB, performed with the help of fiberoptic bronchoscope, are
      needed. The diagnostic power and the limits of both these techniques are
      analyzed. Moreover, the opportunity to obtain quantitative cultures, which may
      discriminate between contamination and infection is considered.

PMID- 8568541
TI  - Bacterial pneumonia in adult patients with HIV infection.
AB  - Patients with HIV infection are at increased risk for community-acquired
      bacterial pneumonias, due in part to their defects in B-cell function.
      Streptococcus pneumoniae is the commonest cause of community-acquired pneumonia,
      with the second most common bacterial agent being Haemophilus influenzae. These
      two organisms account for about two-thirds of community-acquired bacterial
      pneumonias. Frequently bacterial pneumonias appear difficult to distinguish from
      Pneumocystis carinii pneumonia or other opportunistic lung infections, because of
      their atypical clinical and radiologic presentations. Community-acquired
      pneumonias may be recurrent but have low fatality rates. In comparison,
      nosocomial pneumonias occur primarily in patients with AIDS and are usually due
      to Staphylococcus aureus, Pseudomonas aeruginosa and other aerobic gram-negative
      bacilli. Nosocomial pneumonias have high fatality rates. S.aureus is an important
      cause of morbidity and mortality in patients with AIDS and has emerged as a
      secondary opportunist in lungs of patients with opportunistic diseases. While
      appropriate laboratory study is being done, empiric antibiotic therapy should be
      directed against the microorganisms above described.

PMID- 8568542
TI  - The long-term antimicrobial prophylaxis of chronic bronchitis exacerbations.
AB  - Infectious exacerbations are the major cause of mortality in patients with
      chronic bronchitis, particularly in elderly subjects. Considering that the
      preventive use of antibiotics has provided no clear-cut evidence of real
      efficacy, it has become quite common to use treatments potentially able to
      stimulate the immune system for prevention of exacerbations of chronic
      bronchitis. This treatment, based on the oral administration of bacterial
      extracts, should, at least in theory, stimulate the immune defenses and reduce
      the incidence of recurring respiratory tract infections. Although during the last
      few years a good effort to define better the real efficacy and role played by
      bacterial extracts in chronic bronchitis has been made, their clinical
      effectiveness is still the subject of debate and the results of some clinical
      trials are controversial. Particularly, its mechanism of action remains poorly
      understood, although a huge effort has been made in this direction.

PMID- 8568543
TI  - Preclinical and clinical evaluation of once-daily aminoglycoside chemotherapy.
AB  - The rationale for and effectiveness of extended dosage intervals for
      aminoglycosides are reviewed. Aminoglycoside antibiotics have a prolonged
      postantibiotic effect against a variety of common Gram-negative and Gram-positive
      organisms: higher serum aminoglycoside levels are associated with a longer
      postantibiotic effect and increased bactericidal activity. Moreover once daily
      aminoglycoside administration may reduce the potential for adaptive postexposure
      resistance by allowing less contact time between bacteria and antibiotic. A
      longer dosage interval may decrease the risk of nephro- and ototoxicity. At least
      33 published clinical trials suggest that once-daily administration of
      aminoglycosides and conventional regimens involving shorter dosage intervals are
      equally effective in patients with normal renal function and Gram-negative
      infections: besides, once-daily administration may reduce the frequency of
      aminoglycoside toxicity or delay it.

PMID- 8568544
TI  - Once-daily dosing regimen for aminoglycoside plus betalactam combination therapy
      of serious lower respiratory tract infections.
AB  - Aminoglycosides are important antibacterial agents for treatment of serious gram
      negative bacillary infections including lower respiratory tract infection. Once
      daily aminoglycosides result in higher peak and lower trough plasma
      concentrations than conventional multiple daily dosing regimens; once-daily
      aminoglycoside therapy is equally effective, generally less toxic and much less
      expensive and therefore this regimen is more and more frequently used for
      treatment of suspected or confirmed gram-negative bacillary infections and of
      febrile episodes in neutropenic patients, in particular in combination with an
      appropriate betalactam antibiotic. Despite the lack of studies on this topic,
      once-daily aminoglycosides in combination with a betalactam agent can be used in
      subjects with lower respiratory tract infection, including patients with cystic
      fibrosis, in which tobramycin appears to be the aminoglycoside antibiotic of
      choice.

PMID- 8568545
TI  - The place of tobramycin in lower respiratory tract infections (LRTI).
AB  - The Author provides a review of clinical experience with tobramycin as therapy
      for lower respiratory tract infections, in comparison to other aminoglycosides,
      including the pharmacokinetics and toxicity, dwelling on oto- and nephrotoxicity.
      The article includes a discussion of various dosing regimens of the
      aminoglycosides, focussing on efficacy and toxicity arising from once-daily
      administration. The Author then provides a more detailed description of
      tobramycin's pharmacokinetics, indications for its use, and the possibilities of
      once-daily dosing, concluding that toxicity is favorably influenced by a single
      daily administration as well as efficacy, and that patient compliance and reduced
      hospital costs are other advantages of this regimen.

PMID- 8568546
TI  - In vitro postantibiotic effect and postantibiotic leukocyte enhancement of
      tobramycin.
AB  - The occurrence of a postantibiotic effect (PAE) and postantibiotic leukocyte
      enhancement (PALE) of tobramycin, a natural aminoglycoside clinically used since
      the early 1970s, has been investigated in comparison to gentamicin on recent
      clinical isolates of Staphylococcus aureus (both methicillin-susceptible and 
      resistant strains) and of Gram-negative fermenting and non-fermenting rods. A
      concentration-dependent PAE was observed with both antibiotics, regardless of the
      bacterial species used, with some variability based on their intrinsic
      resistance. Tobramycin, at concentrations equal to or higher than the minimum
      inhibitory concentration (MIC), exhibited a rather long PAE (ranging from 1.9 to
      10.9 h) which was often significantly longer than that observed with gentamicin
      (ranging from 1.0 to 7.5h). Moreover, pre-exposure to tobramycin led to enhanced
      polymorphonuclear leukocyte phagocytosis and killing with a 2- to 27-fold
      increase in activity compared to controls. These results suggest that tobramycin
      might be conveniently used with once-daily dosing for the treatment of infections
      due to sensitive pathogens.

PMID- 8568548
TI  - Once-daily tobramycin therapy in lower respiratory tract infections.
AB  - In a multicenter Italian study of 104 adult patients with severe bacterial lower
      respiratory tract infections, the safety and efficacy of a regimen of high dose,
      once-daily tobramycin alone or in combination with antipseudomonas betalactams
      was assessed. The overall bacteriological response was an elimination of the
      original pathogen in 70% of the patients while the overall clinical response
      mirrored the bacteriological results with a successful clinical outcome in 78% of
      patients. Adverse experiences were, in general, few and mild without oto- or
      nephrotoxicity. The once-daily, high dose regimen of tobramycin proved to be a
      safe and efficacious therapy for severe lower respiratory tract infections in
      adult patients.

PMID- 8568547
TI  - Tissue penetration and pulmonary disposition of tobramycin.
AB  - The pharmacokinetics of tobramycin, including the penetration into suction
      blister fluid (SBF), has been investigated in 12 patients with a mean age of 69.8
      +/- 4.6 yrs, after a single i.m. administration of either 150 or 300 mg.
      Tobramycin demonstrated a concentration-independent pharmacokinetics and a high
      diffusion into the extravascular compartment with a penetration index (obtained
      by the SBF and serum AUC ratio) of 135% with no significant differences between
      the two groups of patients. Tobramycin was also administered as a single or
      multiple i.m. dose of 300 mg in 10 intensive care patients undergoing fiberoptic
      bronchoscopy for diagnostic purposes. The aminoglycoside mean concentration 6h
      after the single or last administration ranged from 5.3 to 5.5 mg/l and from 3.0
      to 3.3 mg/l in alveolar lining fluid (ALF) and macrophages (AM), respectively,
      thus demonstrating that the once-daily dosage schedule leads to high and
      persistent levels in the bronchial alveolar tree, exceeding the minimum
      inhibitory concentrations in vitro for susceptible respiratory pathogens.

PMID- 8568549
TI  - Pharmacoeconomic evaluation of once-daily aminoglycoside treatment.
AB  - A special topic in pharmacoeconomics concerns antimicrobial therapy. The cost of
      antimicrobial therapy and an economic evaluation of aminoglycoside antibiotics in
      the last 30 years are reviewed. Some innovative approaches have been found to be
      effective in the control of the use of aminoglycosides and those are: 1)
      selecting the appropriate aminoglycoside, 2) therapeutic drug monitoring and, 3)
      once-daily administration. The practical advantages of once-daily aminoglycoside
      dosing are discussed and the conclusion is that combination therapy continues to
      be a mainstay in several serious Gram-negative infections. Concerns about
      breakthrough infection with extended aminoglycoside dosing intervals can be
      resolved by combination with a betalactam antibiotic. The lower costs associated
      with once-daily aminoglycoside dosing are the consequence of a straightforward
      dosage calculation, a guaranteed peak serum concentration in the therapeutic
      range, potential reduction in treatment period, easier quality control of
      preparation and administration, decreased personnel time, and fewer assays.
      However, some practical considerations remain unanswered.

PMID- 8568550
TI  - Patterns of failure in surgical therapy of medulloblastomas.
AB  - To better understand the relationship between the modalities of the surgical
      ablation of medulloblastomas--partial versus total tumor exeresis--and the
      pattern of tumoral relapse (local regrowth or metastases at distance), we have
      analyzed forty-five children affected by cerebellar medulloblastomas, observed at
      the Policlinico Gemelli, Catholic University Medical School, Section of Pediatric
      Neurosurgery, between 1981 and 1992. According to the entity of the surgical
      exeresis, the patients have been divided in three groups: group I, 25 children
      with complete neoplastic excision confirmed by post-surgical Computed Tomographic
      (CT) scans (total exeresis); group II, 11 patients with minimal tumor residual or
      infiltration in vital areas at the operation, known to the surgeon, but not
      visualized on post-operative CT examination (subtotal exeresis); and group III, 9
      children with a residual tumoral mass, known to surgeon and visualized in the
      immediate postoperative CT scan and further confirmed in late CT controls
      (partial exeresis). Our results confirm that a significant difference in survival
      is observed among patients with total removal, compared to those with subtotal
      and partial tumor exeresis, so stressing the importance of even minimal (not
      detectable at the postoperative CT scan) tumoral brain stem infiltration. The
      analysis of our series shows a different local tumor recurrence rate in the three
      groups of patients, that appear to indicate an inverse relationship between
      degree of tumoral surgical resection and possibility of its local recurrence.
      However, even though a complete removal of the tumor appears associated with a
      minor figure of local recurrence, it does not appear to influence significantly
      the ability of the tumor to metastatize in the long run.

PMID- 8568551
TI  - Surgical management of cerebral cavernous angiomas causing epilepsy.
AB  - Epilepsy is the most frequent presenting symptom in patients with cerebral
      cavernous angiomas. Surgical removal of these vascular malformations causing
      epilepsy is usually recommended for patients with disabling, intractable
      seizures, while conservative management is indicated for neurologically intact
      patients with well controlled seizures. In this paper is reported a retrospective
      series of 36 patients suffering epilepsy from cerebral cavernous angiomas, and
      admitted at our Institution between 1975 and 1992. All patients were surgically
      treated; mortality and morbility were absent. The mean follow-up period was 5.9
      years, since the 36 patients were alive and available for a control review in
      December, 1993. Seizure outcome of the patients resulted in a complete cure of
      the epileptic disorders in 9 (25%), improved seizure control with decreased
      medication in other 11 (30.5%), and epilepsy control with the same preoperative
      therapy in the remaining 16 (44.5%) patients. Furthermore, patients with
      preoperative neurological signs associated to epilepsy resulted improved. The
      authors conclude that surgery, where it is unlikely to cause neurological
      deficits, may allow a definitive cure of epilepsy in patients with cerebral
      cavernous angiomas, preventing the possible risks from hemorrhage and mass
      effect.

PMID- 8568552
TI  - Ruptured cerebral aneurysms operated on with only MRA. Reports of two cases.
AB  - Two cases of ruptured aneurysms of anterior communicating artery were reported.
      The aneuryms were showed only by means of MR angiography and operated on without
      conventional angiography, since patients' allergy to drugs and medium contrast.
      The MRA showed precisely the sites of the aneurysm and the directions of the sac,
      but underestimated the size of the sac. In spite of the lack of angiograms
      induced a great caution during the dissection of the aneurysm and made necessary
      a larger operative field, anyway clipping of the aneurysm's neck was performed
      without great difficulties.

PMID- 8568553
TI  - Intracranial meningioma and astrocytoma in the same patient. Case report and
      review of the literature.
AB  - The authors describe the case of a 58-year-old man with an history of seizures
      because of right parietal parasagittal meningioma. Twenty-two months after
      complete removal of this neoplasm, the patient showed progressive mental
      deterioration and at CT-scans revealed a right temporal anaplastic astrocytoma
      which was operated. In literature the association between intracranial meningioma
      and astrocytoma is reported in 41 cases. After a brief review of the previous
      cases, the authors debate the clinical presentation, the diagnostic problems, the
      aetiopathogenetic hypotheses and the best surgical treatment of this association.

PMID- 8568554
TI  - Percutaneous retrogasserian glycerol rhizolysis for treatment of trigeminal
      neuralgia. Technique and results in 191 patients.
AB  - Percutaneous retrogasserian glycerol rhizolysis (PRGR) became a diffuse and
      valuable method for treatment of trigeminal neuralgia, following its introduction
      by Hakanson in 1981. Its main advantages are: a) mild postoperative facial
      sensory loss, b) simplification of the technique, c) reduction of costs. Our
      results in a series of 191 patients treated between September 1983 and September
      1990 are reported. The procedure was performed according to Hakanson's method
      with minor modifications. In 11 cases (5.7%) we failed to pierce the foramen
      ovale; the procedure was successfully repeated a week or two later. In 17 cases
      it was impossible to obtain CSF from the needle. Complete relief of pain was
      achieved in 177 patients (92.7%), in 124 (64.9%) immediately, in 53 (27.8%)
      within 6 days; the operation was unsuccessful in 14 (7.3%). Postoperative sensory
      evaluation showed: no sensory loss in 33 cases (17.3%); hypalgesia in 8 (4.2%);
      mild hypesthesia in 88 cases (46.1%), confined to the affected divisions in 45
      (23.6%), exceeding it in 43 (22.5%); moderate hypesthesia in 62 cases (32.4%),
      restricted to the target divisions in 36 (18.8%), exceeding them in 26 (13.6%).
      No case of anesthesia occurred. Complications of PRGR were: circum-oral
      ipsilateral herpetic eruption (herpes simplex type), spontaneously and completely
      regressing: 63 cases (33%); minor dysesthesia, seldom reported as painful: 33
      cases (17.3%); impairment of corneal reflex: 19 cases (9.9%), the first branch
      being the target of the treatment in 11; regressive masticatory weakness; 11
      patients (5.7%); aseptic meningitis, promptly regressed: 2 cases (1.0%). Follow
      up ranges from 1 to 7 years (Sept. 1983-Sept. 1990). A recurrence was observed in
      44 cases (23%): in 15 patients (7.8%) a partial relapse occurred, well controlled
      by drug therapy and not requiring further surgical treatment; in 29 cases (15.2%)
      a new percutaneous procedure was required. The mean time of recurrence was 30.5
      months. The recurrence rate in the patients of our series at the end of the
      follow-up period was 23%. Glycerol produces a weak neurolytic lesion, that
      generates minor post-operative facial deafferentation; it is the best technique,
      in our opinion, for treatment of tic douloreux.

PMID- 8568555
TI  - Synaptic degenerative changes in human traumatic brain edema. An electron
      microscopic study of cerebral cortical biopsies.
AB  - The cerebral cortex of 9 patients with complicated brain trauma has been examined
      with the transmission electron microscope to study the distinctive degenerative
      synaptic changes induced by brain injury and associated vasogenic, moderate or
      severe, brain edema. The brain injury and the hematogenous edema fluid
      accumulated in the dilated extracellular space of cerebral cortex neuropil
      induced swelling and shrinkage of pre- and postsynaptic structures, increased
      amount of presynaptic axoplasmic granular substance and clumping, enlargement and
      depletion of synaptic vesicles. In severe brain edema, swollen and shrunken
      presynaptic endings with discontinuous limiting plasma appeared separated from
      the postsynaptic structures and detached from glial ensheathment (synaptic
      disassembly). Post-synaptic shaft dendrites and their spines showed swelling and
      vacuolization. Fragmen-tation and atrophic changes of spine apparatus were found
      in the dendritic spines. The clear and dark types of degeneration were observed
      in most cases examined, in both preand/or postsynaptic structures. Filamentous
      hypertrophy of presynaptic endings was observed only in two cases. Osmiophylic
      bodies, necrotic membranes, lipid inclusions and glycogen granules were seen in
      the synaptic terminals. Disappearance of synaptic densities was evident in some
      cases. Phagocytosis of isolated presynaptic endings or of the entire synaptic
      contacts by astrocytes, microglial cells and by non-nervous invading cells, such
      as monocytes and macrophages, was found.

PMID- 8568556
TI  - Experimental incomplete spinal cord injury: treatment with a combination of
      nimodipine and adrenaline.
AB  - The effect of combination of nimodopine and adrenaline treatment on the motility
      deficits following secondary spinal cord damage was studied. Morphometric axonal
      analyses were also done. Incomplete spinal compression was induced in albino New
      Zealand rabbits anesthetized with ketamine. Neurological deficit was assessed by
      Tarlov's scale. The animals were divided into different groups. In one group the
      animals were anesthetized and subjected to all procedures except spinal cord
      injury and pharmacological treatment. Each of the other groups were divided into
      2 subgroups; the spinal cord compression was induced for 2 min in one subgroup
      and 5 min in other subgroup. The pharmacological treatment in different groups
      consisted of slow intravenous infusions of saline alone, combination of
      adrenaline and nimodipine, nimodipine alone and adrenaline alone. The evolution
      of the motor damage was evaluated by comparing scores obtained with Tarlov's
      scale 1, 24 and 48 hrs after the end of spinal cord compression. In all animals,
      spinal cord compression for 2 and 5 min induced a 5th degree motor deficit.
      Treatment with saline improved slightly the motor deficit. The improvement of
      motor deficit was much better when a combination of nimodipine and adrenaline was
      used. The animals treated with nimodipine alone showed a better recovery in
      comparison with the animals treated with saline alone.

PMID- 8568557
TI  - Supratentorial dermoid cysts. Presentation and management of five cases.
AB  - Five patients with supratentorial dermoid cysts who were surgically treated are
      presented. There were three males and two females, between the ages of 17 and 35
      years (mean 26.6 years). The tumor location was frontobasal and/or temporobasal.
      The duration of illness before the diagnosis ranged from 1 to 14 months (mean 7.4
      months). Clinical presentation included seizures, intracranial hypertension
      syndrome, aseptic meningitis, homonimous lateral hemianopsia, and memory defect.
      Preoperatively, all patients were investigated by computerized tomography (CT);
      in two cases, magnetic resonance (MR) imaging was also obtained. Tumor removal
      was performed by microsurgical procedures; it was total in 3 cases and subtotal
      in the remaining 2 cases. Histologically, all of the tumors exhibited the typical
      dermoid cyst pattern. There were no operative deaths. Two patients experienced
      postoperative language dysfunction and/or hemiparesis. No patient developed
      clinicoradiological evidence of tumor recurrence at 1 to 10 years (mean 5 years)
      following surgery. These results are discussed in light of the data previously
      reported by the literature.

PMID- 8568558
TI  - Spinal cavernous angioma producing subarachnoid hemorrhage. Case report.
AB  - A case of subarachnoid hemorrhage due to intramedullary cavernous angioma at the
      T9 level is presented. Literature dealing with subarachnoid hemorrhage due to
      intraspinal lesions is reviewed. The majority of cases of spinal subarachnoid
      hemorrhage are due to arteriovenous malformations, whereas bleeding by cavernous
      angioma is extremely rare. The subarachnoid hemorrhage is rare event (1.8%) in
      our series too. The clinical presentation of severe back pain with radicular
      component associated with signs of meningism (Fincher's syndrome) led us to carry
      out magnetic resonance imaging. This gave accurate diagnosis for surgical
      treatment. Laminectomy at T9-T10 level and total microsurgical removal of the
      vascular malformation were performed with total functional recovery.

PMID- 8568559
TI  - Spinal epidural lipomatosis as a complication of prolonged corticosteroid
      therapy.
AB  - We present the case of a 42-year-old man who complained of low back pain
      radiating into the posterior aspect of both thighs. There were no neurological
      deficits, while general medical examination revealed a Cushing's syndrome due to
      corticosteroid therapy for rheumatic polyarthritis. Myelography showed irregular
      and circumferential narrowing of the dural sac from L-3 to S-1 caused by abundant
      epidural fat as demonstrated by MRI. Surgical decompression produced immediate
      relief of symptoms. The literature of epidural spinal lipomatosis is reviewed and
      therapeutic considerations are discussed.

PMID- 8568560
TI  - Spinal epidural hematoma during anticoagulant therapy. A case report and review
      of the literature.
AB  - The authors present a case of spinal epidural hematoma during anticoagulant
      therapy. Clinical presentation is characterized by classic paravertebral back
      pain, followed by progressive neurological deficit due to spinal cord and
      radicular compression, with sensory deficits and bladder disturbance. From the
      literature, 37 cases are collected of spinal epidural hematoma during
      anticoagulant therapy, treated surgically. Pathogenesis, diagnosis, and
      differential diagnosis are discussed. Early surgical decompression of the spinal
      cord minimizes the degree of permanent neurological damage, because of the long
      time compression of the spinal cord resulting in irreversible disturbance of
      circulation; therefore an early diagnosis is a better prognosis. The thoracic and
      cervical spine canal is smaller than the lumbar, therefore there is less space to
      reward the formation of hematomas, consequently the postoperative recovery is
      lower in patient with high spinal epidural hematomas with respect to lumbo-sacral
      spinal epidural hematomas; at this level the epidural hematoma may be insidious
      in its onset and tends to become chronic before definite treatment is undertaken.

PMID- 8568561
TI  - Synthetic low-molecular weight thrombin inhibitors: the ideal antithrombotic
      drug? An introduction.

PMID- 8568562
TI  - The X-ray crystal structure of thrombin in complex with N alpha-2
      naphthylsulfonyl-L-3-amidino-phenylalanyl-4-methylpiperidide: the beneficial
      effect of filling out an empty cavity.
AB  - The 2.5 Angstrum structure of bovine epsilon-thrombin in complex with N alpha-2
      naphthyl-sulfonyl-L-3-amidinophenylalanyl-4-methylpiper idide (L-NAPAMP) was
      solved and crystallographically refined to an R-value of 0.19. The L-NAPAMP
      moiety is completely and unambiguosly defined in the electron density. NAPAMP
      binds almost identical to the related 4-methyl deficient 3-amidino-phenylalanyl
      derivative TAPAP. The overall binding geometry appears dominated by the fixation
      of the 3-amidinophenyl ring in thrombin's S1-pocket and the hydrogen bonds to Gly
      216, irrespective of the presence or absence of a substituent in the 4-position
      of the piperidine ring. The additional 4-methyl group gives rise to a 17-fold
      better binding. The more complete spatial occupancy of the hydrophobic S2-cavity
      therefore accounts for a decrease in free energy of binding of 15 kcal/mol, a
      value comparable with that anticipated for filling up a stable empty cavity of
      similar size by a methyl group.

PMID- 8568563
TI  - Inhibition of thrombin by arginine-containing peptide chloromethyl ketones and
      bis chloromethyl ketone-albumin conjugates.
AB  - Arg-containing peptide chloromethyl ketones including D-Phe-Pro-Arg-CH2Cl
      derivatives have been synthesized and tested as inhibitors for thrombin and
      several blood coagulation enzymes. The parent compound, D-Phe-Pro-Arg-CH2Cl is
      still the best thrombin inhibitor in the series with kobs/[I] value of 10(7) M-1s
      1. Extension by one amino acid (Phe or Gly), or a peptide moiety (ClCH2-Arg < 
      Pro < -D-Phe < -CO-CO-, ClCH2-Arg < -Pro < -D-Phe < -CO-(CH2)3-CO-, where < 
      indicates a reversed amino acid residue, -CO-CHR-NH-) on the N-terminus of D-Phe
      Pro-Arg-CH2Cl reduces the inhibition constant by 1-2 orders of magnitude, which
      indicates the importance of a free amino group at the N-terminus. The tripeptide
      D-Phe-Pro-Arg-CH2Cl and related tetrapeptide inhibitors inhibit thrombin more
      potently than factor IXa and plasma kallikrein by 2-5 orders of magnitude. Z-Arg
      CH2Cl and Phe-Phe-Arg-CH2Cl which contain a large hydrophobic group at the P2
      site inhibit thrombin poorly. All the peptide chloromethyl ketones inhibit plasma
      kallikrein moderately with kobs/[I] values of 10(2)-10(3) M-1s-1 but inhibit
      factor IXa poorly (kobs/[I] < 20 M-1s-1). Conjugates of albumin with the bis
      chloromethyl ketones [(CO-D-Phe-Pro-Arg-CH2Cl)2, (CH2)3-(CO-D-Phe-Pro-Arg
      CH2Cl)2] were prepared and are potent thrombin inhibitors. These conjugates are
      model compounds for developing specific thrombus-bound thrombin inhibitors which
      may have therapeutic application in the treatment of coagulation disorders.

PMID- 8568564
TI  - Structure/function aspects of neutral P1 residue peptide inhibitors of thrombin.
AB  - Control of thrombin by its inhibition in indications such as myocardial
      infarction, unstable angina or stroke has been demonstrated to be therapeutically
      valuable. However restoration of hemostasis by targeting thrombin while avoiding
      its fellow serine proteinases, (e.g. plasmin, trypsin), remains a challenge of
      medicinal chemistry. Tripeptide-boronates and -phosphonates with neutral P1 side
      chains meet these criteria. Development of novel, high yielding chemical routes
      furnishes a wide range of un-natural P1 functionalities, demonstrating that this
      indeed is a class effect with selectivity conferred by the uncharged P1 residue.
      For example N-benzyloxycarbonyl-D-phenylalanylprolyl-1- (3-methoxypropyl)
      boroglycine ester (1) has a Ki value for thrombin of 7 nM and greater than two
      order of magnitude higher with all other serine proteinases tested. The ester
      group determines the kinetics of inhibition by tripeptide phosphonates, with
      diphenylphosphonates being slow tight binding inhibitors, showing 50%
      reversibility of inhibition. Therefore this design of inhibitors offers a facile
      strategic approach to development as thrombin specific pharmaceutical agents.

PMID- 8568565
TI  - Thrombin inhibitors as antithrombotic agents: the importance of rapid inhibition.
AB  - For use as an antithrombotic agent, a thrombin inhibitor must be potent and
      specific, i.e., it should not significantly inhibit the proteases of the
      anticoagulation (activated protein C) and fibrinolytic systems (plasminogen
      activator and plasmin). Previous evaluation of potency and specificity has been
      based on inhibition constants (Ki values). However, consideration of the kinetic
      parameters for natural plasma serine protease inhibitors indicates that a low Ki
      value with thrombin is not sufficient; the inhibited complex must also form
      rapidly. Moreover, potent inhibition of activated protein C and plasmin could be
      tolerated providing the inhibited complex only forms slowly. An ideal profile of
      kinetic parameters with thrombin, activated protein C and plasmin is formulated
      and discussed in relation to various classes of thrombin inhibitors. Examination
      of kinetic data for thrombin inhibitors currently in clinical trials (hirudin and
      hirulog) indicates that they possess this ideal profile of kinetic parameters.

PMID- 8568566
TI  - Thrombin inhibitors based on ketone derivatives of arginine and lysine.
AB  - Much attention is currently focused on inhibitors of thrombin as potential
      anticoagulants. We have previously reported thrombin inhibitors based on
      fragments of fibrinogen containing a ketomethylene isostere at P1-P'1. We now
      expand on these early findings by reporting on tripeptide based inhibitors of
      thrombin containing arginine or lysine ketones at the C-terminus. A large variety
      of such ketones have been studied and compared in their ability to increase the
      thrombin time in human plasma. In the case of arginine or lysine ketones the
      order of activity (i.e. decreasing IC50 TT) was: alkyl ketones < beta-ketoesters
      < difluoro beta-ketoamides < alkyloxymethyl ketones < fluoroketones. Lysine
      analogues were generally found to be ca. ten-fold less active than their arginine
      counterparts. However, in the case of alpha-ketoesters the lysine derivatives
      were superior to all the types of arginine ketones studied (including the
      arginine alpha-keto ester derived thrombin inhibitor). A mechanistic explanation
      of the relative inactivity of the arginine alpha-keto ester derivative is
      proposed. All the highly electrophilic ketones were found to be slow-binding with
      thrombin.

PMID- 8568567
TI  - Synthesis and characterisation of novel thrombin inhibitors based on 4
      amidinophenylalanine.
AB  - Thrombin inhibitors have been thought to play a pivotal role in myocardial
      infarct and stroke incidences and their aftermath. Quite some time ago potent
      synthetic thrombin inhibitors became known based on peptide derivatives D-Phe-Pro
      Arg and benzamidine. One of them, fairly well characterised was beta
      naphthylsulphonylglycyl-D,L-4-amidino-phenylalanylpiperidi de (NAPAP). NAPAP was
      prone to being administered intravenously due to its short plasma half life.
      Drawbacks to this compound such as effects on histamine release and blood
      pressure may have obstructed its clinical use. Long half life and oral
      bioavailability would be desirable for prophylactic treatment of thrombotic
      disorders. We have used NAPAP as a template for new synthetic compounds to
      improve some characteristics of its profile. For screening purposes we have
      investigated fairly simple surrogate parameters, aspects that were considered to
      contribute to pharmacological effects. Potency was correlated to thrombin
      inhibition, side effects were addressed by specificity toward thrombin as well as
      reduction in basicity, and plasma half life was considered to be modulated by
      plasma stability of the compound. Oral bioavailability would be affected by
      instability during the passage through the gut wall. Chemical introduction of a
      carboxylic group and exchange of the naphthyl group for 4-methoxy-2,3,6
      trimethylphenyl led to a compound that when compared to NAPAP, exhibited a 4-fold
      increase in thrombin inhibitory activity and a 3-fold increase in trypsin
      specificity. Plasma stability decreased to 22 h, however, sufficient enough not
      to play a major role in plasma half life. Gut homogenate stability of the
      compound has not changed. The potency increase did not translate into a reduction
      in IC50-values for the coagulation assay aPTT and TT, in contrast to the IC50
      values for thrombin-induced platelet aggregation.

PMID- 8568568
TI  - Design, synthesis and biological activity of novel rigid amidino-phenylalanine
      derivatives as inhibitors of thrombin.
AB  - (3S)-(Naphthalene-2-sulfonylamino)-1-[2R-(4-amidinophenyl)-1-
      piperidinocarbonylethyl]-2-pyrrolidinone (1a) is a potent inhibitor of thrombin
      with an IC50 value by 112 times lower than that of NAPAP (racemate). The
      selectivity versus trypsin can be improved by incorporation of substituents on
      the naphthyl ring. The mode of binding of the compound was determined by X-ray
      crystallography.

PMID- 8568569
TI  - Structure-activity relationships of inhibitors derived from 3
      amidinophenylalanine.
AB  - Thrombin is the key enzyme in coagulation and its inhibitors are of therapeutic
      interest since they are potential anticoagulants. The most potent inhibitor of
      the benzamidine type is N alpha-(2-naphthylsulfonyl-glycyl)-4
      amidinophenylalanine piperidide (NAPAP). However, NAPAP and other substances
      designed so far do not fulfill the pharmacological requirements. The goal of
      designing new compounds was to obtain potent inhibitors with improved
      pharmacokinetic properties, such as absorption after oral application and a
      sustained elimination. Novel derivatives of 3-amidinophenylalanine as key
      building block were synthesized. The amidino moiety and both the N alpha- and the
      C-terminal substituents were widely varied. Some of the newly synthesized
      compounds are potent inhibitors of thrombin and exert improved pharmacokinetic
      properties.

PMID- 8568571
TI  - A home study program on home birth.

PMID- 8568570
TI  - Home birth. The delivery of safe and satisfying care to women and their families.

PMID- 8568572
TI  - Home birth in the United States, 1989-1992. A longitudinal descriptive report of
      national birth certificate data.
AB  - This study was conducted to profile home birth in the United States from 1989 to
      1992 using two birth certificate data sources from the Natality Branch of the
      National Center for Health Statistics (NCHS). Analysis included published and
      unpublished descriptive tables about all U.S. home births from 1989 to 1992, and
      a subset of the 82,210 U.S. home births from 1989 to 1991 that were drawn from
      NCHS national birth certificate data tapes. Results indicated that less than one
      third of reported home births were attended by nurse-midwives or physicians.
      Distinct regional patterns in the frequency of home births were observed, with
      higher concentrations in the southwestern and western states. When compared with
      the average childbearing woman in the United States, mothers who gave birth at
      home were more likely to be older, have fewer years of education, be married, and
      be white; they were also more likely to be of higher parity and to receive less
      prenatal care. Home birth mothers were less likely than average to smoke or drink
      alcohol prenatally, to have a prenatal medical risk condition or an obstetric
      complication, or to receive certain prenatal tests. The outcomes of newborns born
      at home compared favorably to the national average during the same period.
      Several findings varied considerably by race or ethnicity of the mother.

PMID- 8568573
TI  - Outcomes of 11,788 planned home births attended by certified nurse-midwives. A
      retrospective descriptive study.
AB  - This study describes the outcomes of 11,788 planned home births attended by
      certified nurse-midwives (CNMs) from 1987 to 1991. A retrospective survey was
      used to obtain information about the outcomes of intended home birth, including
      hospital transfers, as well as practice protocols, risk screening, and emergency
      preparedness. Ninety nurse-midwifery home birth practices provided data for this
      report (66.2% of identified nurse-midwifery home birth practices). It is
      estimated that 60-70% of all CNM-attended home births reported in national
      statistics data during this period were represented in this survey. The overall
      perinatal mortality was 4.2 per 1,000, including known third-trimester fetal
      demises. There were no maternal deaths. The intrapartum and neonatal mortality
      for those intending home birth at the onset of labor was 2 per 1,000; the overall
      neonatal mortality rate for this group was 1.3 per 1,000. When deaths associated
      with congenital anomalies were excluded, the intrapartum and neonatal mortality
      rate was 0.9 per 1,000; the neonatal mortality was 0.2 per 1,000. The overall
      transfer rate, including antepartum referrals, was 15.9%. The intrapartum
      transfer rate for those intending home birth at the onset of labor was 8%. Most
      responding nurse-midwives used standard risk-assessment criteria, only delivered
      low-risk women at home, and were prepared with emergency equipment necessary for
      immediate neonatal resuscitation or maternal emergencies. This study supports
      previous research indicating that planned home birth with qualified care
      providers can be a safe alternative for healthy lower risk women.

PMID- 8568574
TI  - Home birth with certified nurse-midwife attendants in the United States. An
      overview.
AB  - The move of the birth site from home to hospital in the United States from 1800
      through the early part of the 20th Century is described. The reemergence of home
      birth in the United States since the early 1960s and the evolution of nurse
      midwifery care in the home birth setting are discussed. Misconceptions regarding
      home birth and a review of international literature documenting the safety of
      home birth are included. The need for prospective research on home birth is
      supported. A Home Birth Curriculum Guide developed by the Home Birth Committee of
      the American College of Nurse-Midwives is provided.

PMID- 8568575
TI  - Guidelines for client selection in the home birth midwifery practice.
AB  - Numerous studies have documented the safety of planned home birth; yet, few have
      identified specific criteria for selection of the home birth candidate. Home
      birth midwifery practice achieves successful outcomes by appropriate evaluation
      of medical and obstetric risk factors, as well as an ongoing evaluation and
      development of the client's psychosocial resources and the midwife-client
      relationship. Relevant medical and obstetric factors include significant medical
      illnesses, antenatal course, smoking history, commitment to breastfeeding, and
      the woman's nutritional profile. Social and environmental factors include the
      need for a stable birthing environment, practical means for hospital transfer,
      and the presence of loving support for the client during and after delivery. The
      client's psychological preparedness is a critical variable that may affect the
      ability to deliver in the home setting without analgesia or labor augmentation.
      Active participation in prenatal care, preparation of the home and family
      members, and a realistic attitude regarding the risks, benefits, and potential
      complications of planned home delivery are all components of this preparedness.
      Because midwifery practice promotes midwife-client rapport by careful attention
      to both medical and psychosocial issues during prenatal care, this relationship
      is itself an important predictor of the client's suitability for home birth. The
      quality of midwife-client interactions may influence not only the decision to
      plan a home birth but the indications for hospital transfer should problems
      arise. In this article, existing literature is reviewed and criteria are proposed
      for selecting home birth candidates within the American midwifery practice
      setting.

PMID- 8568576
TI  - Preparing couples for home birth. Practical suggestions.
AB  - Parents planning a home birth need specific information beyond that which
      typically is covered in childbirth preparation classes geared for hospital
      couples. Topics that specifically need to be included in preparation for home
      birth include the meaning of shared responsibility for the birth at home,
      informed disclosure of personal and professional data, motivating factors and
      barriers to a successful birth, coping strategies, preparation of the home
      environment, contingency plans for referral or emergency transport, and
      preparation for self-care following the birth.

PMID- 8568577
TI  - Neonatal considerations when birth occurs at home.
AB  - Certified nurse-midwives who attend births at home have special responsibilities
      and need to maintain certain skills that are designed to promote neonatal well
      being. These include careful screening prior to and during labor to be sure that
      only the lowest risk women attempt home birth, resuscitation skills more polished
      than those required in hospital settings, and a high degree of skill in
      evaluation of the newborn following birth.

PMID- 8568578
TI  - Care of the at-risk neonate born at home. A model for nurse-midwife/physician
      collaboration.
AB  - Because certified nurse-midwives (CNMs) who practice in the home lack the
      structure and boundaries provided in an institution, they must provide the
      elements of a safe environment for their practice, both physical and intangible.
      The relationship between the CNM who practices in the home and the physician(s)
      with whom s/he collaborates when women or neonates experience complications
      beyond the scope of nurse-midwifery practice is a critical element of this
      structure. This paper describes models for collaborative care for home birth,
      outlines the process of developing a collaborative practice agreement, and
      discusses specific factors to consider when forming a relationship. The care of
      the compromised home-birth neonate is developed as a model for collaborative
      practice. The paper discusses identification of the home-birth neonate requiring
      collaborative care, the preparation for potential newborn complications, and the
      initiation of emergency measures to be taken by the CNM when such a complication
      occurs.

PMID- 8568579
TI  - Informed consent and home birth.
AB  - The history and purpose of informed consent are explored and its legal components
      are detailed. Recommendations are given to meet the criteria for informed
      decision-making at home, including discussion of unusual circumstances. The
      nature of assistance at childbirth, especially at home, is explored in relation
      to legal obligations. The article includes some observations on cultural
      dissonance regarding informed consent. Finally, the authors recommend a focus on
      a therapeutic alliance with the client as the best outcome of effective informed
      consent and as the second best preventive measure against malpractice, the first
      being competent care.

PMID- 8568580
TI  - In pursuit of excellence: quality assurance, documentation, and peer review by
      home birth CNMs.
AB  - The unique characteristics of home birth practice for certified nurse-midwives
      (CNMs) are applied to a quality assurance program. This article explores the
      mUltiple purposes, benefits, and elements of documentation as they specifically
      apply to home birth. The steps of documentation for a home birth practice are
      outlined and the three current models to consider in setting up positive peer
      review programs in which CNMs can succeed and learn are presented.
      Recommendations are made for 1) a more positive emphasis on the purposes of
      documentation and collection of statistics, 2) networking to close the gaps of
      isolation and task duplication for home birth CNMs, 3) ongoing development of
      models for positive peer review to facilitate participation in the mandate of the
      American College of Nurse-Midwives, and 4) identification of clinical indicators
      for quality assurance specific to home birth practice by CNMs.

PMID- 8568581
TI  - [Expression of glycoconjugates in laryngeal cancer].
AB  - Using the six lectins PNA, SNA, WGA, UEA-1 Amaranthin, and MAA, a cytochemical
      study was performed to observe the expression of glycoconjugates in squamous cell
      carcinomas of the larynx in 14 patients and in 3 normal laryngeal epithelia. SNA
      (Sambucus nigra agglutinin) failed to stain the cytoplasm in normal squamous
      epithelium of the larynx, but the cytoplasm of the epithelial dysplasia and
      carcinoma cells reacted to SNA, showing more intensely stained cytoplasma of
      carcinoma as compared to those of the epithelial dysplasia. PNA (Peanut
      agglutinin) specifically stained cell membranes of middle layer and basal cells
      in the normal squamous epithelium and epithelial dysplasias, but in squamous cell
      carcinomas, a lack of cell membrane staining of various degrees was noted. There
      was a similarity in the other lectin staining expressions in the normal controls
      and epithelial dysplasia and carcinoma. The expression of these six lectins was
      not related to the TNM-classification. Lectin staining may be a useful marker in
      either early diagnosis of cancer or the assessment of cellular differentiation.

PMID- 8568582
TI  - [Effects of transcutaneous silicon injection for aspiration caused by unilateral
      vocal cord paralysis].
AB  - The purpose of this study was to determine the effects of transcutaneous silicon
      injection on swallowing function in unilateral vocal cord paralysis with
      aspiration. The preoperative and postoperative swallowing function were evaluated
      by means of videofluoroscopy and pharyngeal manometry in eight patients who
      received injection of silicon into the laryngeal vestibule, ventricle and vocal
      cord. Data analysis compared 1) types of aspiration and pharyngeal clearance, 2)
      timing of laryngeal closure (complete closure between arytenoid and epiglottic
      base) that was correlated with the onset of cricopharyngeal (CP) opening as time
      zero, and 3) swallowing pressure in the pyriform sinus on the side of the
      paralyzed vocal cord. In seven of the 8 patients, a favorable clinical response
      was achieved and aspiration and/or penetration were not observed on the
      fluoroscopic images after the silicon injection. Timing of laryngeal closure
      could be quantified in six patients, and mean values of the times preceding the
      onset of CP opening were significantly earlier on the postoperative examinations
      than preoperative examinations. Pharyngeal clearance on the affected vocal cord
      side was improved in six of the 8 patients, and swallowing pressure in the
      pyriform sinus was significantly elevated in four patients following surgery.
      These results suggested that silicon injection therapy produced earlier laryngeal
      closure during the swallow and improvement of pharyngeal clearance on the
      affected side after the swallow, so that aspiration and/or penetration with vocal
      cord paralysis might be prevented.

PMID- 8568583
TI  - [A study on button-type alkali-manganese battery in Ringer's solution--limited
      injury factor on the electric discharge in body].
AB  - Many cases of tissue injury caused by a button battery appearing as a foreign
      body have been reported in the otolaryngology field. However, there have been
      very few studies on the mechanism of tissue injury by batteries. In this study,
      we inserted a button-type battery into 4cm3 of Ringer's solution, which is
      similar to serous fluid, at both room temperature (20 degrees C) and body
      temperature (37 degrees C), and observed the electro-chemical reactions between
      the negative and positive terminals over 6 hours. We identified the products of
      these reactions, measured the remaining electromotive force (EMF), and observed
      the changes in pH and metallic ion concentrations over time. In conclusion, the
      following three major groups of factors causing tissue injury were suggested: 1)
      At the positive terminal the HCl acid and HClO produced broke down, and chlorine
      gas was dissolved into the solution. 2) At the negative terminal, the OH- radical
      was produced by reduction of water. 3) Potassium hydroxide (KOH), nickel (Ni2+),
      manganese (Mnn+), chrome (Crn+), and lead (Pb2+) leaked from the battery at the
      poles, due to oxidation, and were partially dissolved in the serous fluid. These
      factors may result in serious tissue injury. In addition, each electro-chemical
      reaction occurred in a very short time at these relatively high temperatures, and
      as a result, may be the cause of these tissue injuries.

PMID- 8568584
TI  - [Hearing results after anterior tympanotomy in cholesteatoma surgery].
AB  - Between 1987 and 1993, 71 ears of attic type cholesteatoma and 20 ears of
      adhesive type were operated on using the intact canal wall technique combined
      with anterior tympanotomy. Pre- and postoperative pure tone hearing after the
      surgery were analyzed, especially to determine whether anterior tympanotomy is
      harmful to the inner ear. Mean values of 500, 1000 and 2000Hz of air conduction
      threshold immediately, before and about 1 year after the operation were compared.
      In attic cholesteatoma, type 1, type 3, and type 4 of ossiculoplasty revealed
      significant improvement of 8.4dB, 9.3dB, and 8.0dB respectively. In adhesive
      cholesteatoma, results obtained were 8.4dB, 0.8dB, and -3.0dB. Differences
      between pre- and postoperative bone conduction threshold at 4000Hz were 1.5dB in
      type 1, 1.3dB in type 3, and 5.0dB in type 4 in attic cholesteatoma. Those in
      adhesive cholesteatoma were -2.5dB, -0.2dB, and -10.0dB respectively. From the
      results obtained, we concluded that (1) our results were satisfactory with
      regards to hearing ability following all types of ossiculoplasty in attic
      cholesteatoma and in type 1 in adhesive cholesteatoma, (2) anterior tympanotomy
      itself is not a harmful procedure to the inner ear in both types of
      cholesteatoma, (3) an increase in bone threshold in adhesive cholesteatoma is due
      to the surgical procedure at the stapes and/or the oval window.

PMID- 8568585
TI  - [Subcortical pathways related to optokinetic nystagmus in the cat].
AB  - In recent experiments, it has been disclosed that the nucleus of the optic tract
      (NOT) is the visut-motor relay between the retina and preoculomotor structures in
      the pathway mediating optokinetic nystagmus (OKN). In the present study, how OKN
      signals are transmitted from the NOT in the brainstem was investigated using
      biocytin and triticum vulgaris (Wheat Germ) peroxidase labeled (WGA-HRP) as
      anterograde and retrograde tracers, respectively. Following biocytin injections
      into the NOT, labeled fibers were observed in each of the following efferent
      pathways: 1) those that project to the contralateral NOT via the posterior
      commissure; 2) those that course through the nucleus pontis orklis to terminate
      in the Edinger-Westphal complex and nucleus reticularis tegmenti pontis; and 3)
      those that descend via the medical lemniscus to the level of the medulla to
      terminate in the dorsal cap of the inferior olive, during which their axons
      branch to the dorsolateral pontine nucleus, nucleus prepositus hypoglossi, and
      the nucleus pontis caudalis, superior and lateral. Furthermore, differences in
      the distribution of labeled cells in the NOT were observed following WGA-HRP
      injections into the nucleus prepositus hypoglossi and medial vestibular nucleus.
      The retrograde labeled cells in the NOT were distributed to the medial area at
      the rostral level following the tracer injections into the medial vestibular
      nucleus. On the other hand, labeled cells were recognized in the part of the
      caudal NOT following the tracer injections into the nucleus prepositus
      hypoglossi. A recent neurophysiological study demonstrated that areas adjacent to
      the medial vestibular nucleus apparently to participate in the production of OKN,
      because both the slow component and after-nystagmus similar to OKN and
      optokinetic after nystagmus were elicited by stimulation of the vestibular
      nuclei. The present study shows that this direct projection from the NOT to the
      vestibular nuclei may serve to drive velocity storage in the vestibular nuclei.

PMID- 8568586
TI  - Out of the Hodgkin's maze?

PMID- 8568587
TI  - Low versus high cell turnover in diffusely growing non-Hodgkin's lymphomas.
AB  - Cell loss, perhaps as important as cell production in determining the size of an
      expanding cell population, has not usually been registered in quantitative
      cellular kinetic analyses of neoplastic disorders. The present retrospective
      study on various types and subtypes of non-Hodgkin's lymphomas (NHLs; n = 170)
      was designed to test the usefulness of a novel additional parameter, the
      'turnover index' (TI), which is the sum per case of the mitotic index and the
      apoptotic index. Results document that TIs clearly distinguished between
      categories and subtypes of NHLs according to the Kiel classification. Cluster
      analysis of TIs plotted against the percentage of Ki-67-positive cells per case
      revealed that about one-third of the high-grade malignancy lymphomas actually
      belonged to the low-turnover lymphomas. Overall survival was longer in the low-
      than in the high-turnover group of lymphomas. Assessment of TIs can, for
      practical diagnostic purposes, be replaced by counting mitotic figures and
      apoptotic cells in several high-power fields. The TI concept may help to
      interpret the kinetics of NHLs in terms of accumulation vs. proliferation of
      cells.

PMID- 8568588
TI  - Long-term follow-up in early gastric cancer: evaluation of prognostic factors.
AB  - Four hundred and fourteen cases of early gastric cancer (EGC), diagnosed between
      1977 and 1993, were studied. The percentage of EGC increased from 1977 to 1984,
      but thereafter remained more or less stable, despite a continuous increase in the
      number of endoscopic examinations. Three hundred and ninety-six patients were
      followed up. Twenty-nine patients died from the tumour, giving a 5-year survival
      rate of 82.8 per cent. The 'large' size type of EGC, the presence of submucosal
      penetration, and lymph-node metastasis showed a highly significant association
      with a lower survival rate. A small number of patients died despite the presence
      of 'favourable' prognostic factors. Other still unknown factors may therefore be
      important in determining the aggressive behaviour of certain EGCs.

PMID- 8568589
TI  - Expression of basic fibroblast growth factor and fibroblast growth factor
      receptor in advanced gastric carcinoma.
AB  - The expression of basic fibroblast growth factor (bFGF) and fibroblast growth
      factor receptor (FGFR) mRNA was examined in gastric carcinomas by
      immunohistochemistry and in situ hybridization, respectively. In the 20 advanced
      carcinomas examined, bFGF was found in 14 (70.0 per cent) and was confined to the
      tumour cells, whereas FGFR mRNA was demonstrated in 12 (60.0 per cent) and seen
      in both tumour cells and endothelial cells. The bFGF and FGFR mRNA-positive
      carcinomas were larger, were more frequently classified as undifferentiated
      adenocarcinoma, more frequently invaded the serosal layer, and had a higher rate
      of lymph node metastases than the bFGF and FGFR mRNA-negative carcinomas.
      Patients with bFGF and FGFR mRNA-positive carcinomas appear to die earlier than
      those with bFGF and FGFR mRNA-negative tumours. The values for the carcinomas
      that were positive for either bFGF or FGFR mRNA fell between these two groups.
      The findings suggest that the autocrine/paracrine bFGF/FGFR channel is associated
      with undifferentiated gastric carcinomas and may lead to a poorer prognosis.

PMID- 8568591
TI  - The increased expression of adhesion molecules ICAM-3, E- and P-selectins on
      breast cancer endothelium.
AB  - Sequential interaction of neoplastic cells with the endothelium of tumour
      neovasculature is believed to be a significant step in tumour metastasis.
      Increasing evidence suggests that inducible endothelial adhesion molecules are
      intimately involved in this process. An immunohistochemical approach was used to
      examine the expression of adhesion molecules in 14 normal controls and a series
      of 64 invasive breast carcinomas. Endothelium in normal breast showed
      constitutive expression of PECAM (100 per cent), ICAM-2 (100 per cent), and P
      selectin (64 per cent); variable and focal expression of ICAM-1 (71 per cent);
      and only weak staining for E-selectin (21 per cent). No ICAM-3 or VCAM-1
      expression was observed. Similarly to normal breast endothelium, widespread and
      intense immunoreactivity on the endothelium of tumour-associated vessels was seen
      for PECAM (100 per cent), ICAM-1 (69 per cent), and ICAM-2 (95 per cent). In
      contrast to normal tissues, E- and P-selectins showed increased intensity of
      staining (52 and 67 per cent of cases, respectively) and expression of E- and P
      selectins was more prominent at the tumour periphery. ICAM-3 expression was
      increased on tumour endothelium (15 per cent of cases), but in common with VCAM-1
      (10 per cent) expression was focal. A previously unreported finding was the
      immunoreactivity of the neoplastic epithelial cells for the non-epithelial
      lineage markers ICAM-1 (34 per cent), ICAM-3 (10.9 per cent), PECAM (1.6 per
      cent), and E- and P-selectins (7 and 37 per cent of cases, respectively). These
      findings show that tumour endothelium displays significant heterogeneity and can
      assume a pro-inflammatory phenotype, probably as a result of cytokine
      stimulation. Upregulation of adhesion molecules might contribute to changes in
      invasive phenotype by promoting endothelial cell adhesion and angiogenesis, as
      well as forming a substratum for tumour cells to assemble and attract
      macrophages.

PMID- 8568590
TI  - Standard and variant CD44 isoforms are commonly expressed in lung cancer of the
      non-small cell type but not of the small cell type.
AB  - Cluster of differentiation 44 (CD44) encompasses a polymorphic family of cell
      membrane glycoproteins involved in the mechanism of tumour invasion and
      metastasis. Since non-small cell lung cancer (NSCLC) and small cell lung cancer
      (SCLC) display very different rates of progression, a significant discrepancy in
      their CD44 expression profiles is to be expected. An immunohistochemical study
      was undertaken on the expression of standard CD44 (CD44s) and the variant
      isoforms containing the domains encoded by variant exon 3 (CD44v3) or variant
      exon 6 (CD44v6) in paraffin-embedded bronchial biopsy specimens from 32 NSCLC
      cases and 11 SCLC cases. An absolute lack of immunoreactivity for CD44s, CD44v3,
      and CD44v6 was obtained in every case of SCLC, whereas 28 of the 32 NSCLC cases
      showed a positive immunoreaction for at least one of the three epitopes
      investigated. In conclusion, the occurrence of standard and variant CD44 isoforms
      in NSCLC and their absence in SCLC suggest the possibility that CD44 is in some
      way instrumental in conditioning the biological behaviour of NSCLC, but not of
      SCLC, whose metastatic cascade would be set in motion by the activation of
      hitherto unidentified, CD44-independent pathways.

PMID- 8568592
TI  - Identification of a low-risk group of stage I breast cancer patients by
      cytometrically assessed DNA and nuclear texture parameters.
AB  - Image cytometrical measurements were performed on Feulgen-stained cells from 329
      stage I breast cancers (pT1pN0,M0,R0). For each patient, several DNA (ploidy, S
      phase fraction, exceeding rates, 2c deviation index, ploidy balance, entropy, and
      histogram typing), morphometric (area and radius of nuclei), and textural
      parameters (mainly co-occurrence and run-length) were calculated. The prognostic
      value of these parameters was investigated by multivariate Cox regression
      analysis, considering a distant recurrence-free survival of 8 years as the
      prognostic criterion. In the multivariate analysis, one DNA parameter (histogram
      type) and two textural parameters (co-occurrence and variation of the average
      heterochromatin area) were proven to have independent prognostic value. Using a
      linear combination of these variables, a prognostic factor was calculated for
      each individual patient. Patients were stratified using this factor into several
      groups according to their risk for distant recurrence. Thus, a low-risk group of
      stage I patients was identified, remaining distant recurrence-free for 8 years.
      In addition, a group of patients with a worse prognosis and an 8-year recurrence
      rate of about 26 per cent was identified, compared with the average distant
      recurrence rate of all stage I patients of 13 per cent. A combination of DNA and
      textural parameters can provide powerful prognostic information in stage I breast
      carcinomas and may allow a better selection of patients for different therapy
      protocols.

PMID- 8568593
TI  - Grading of precancerous laryngeal lesions by multiparameter image analysis at
      separate epithelial layers.
AB  - In order to detect early precancerous changes which do not involve the whole
      thickness of the epithelium, we used a novel image analysing program based on an
      IBAS system (Kontron, Germany) to determine nuclear DNA content (NC) as well as
      average nuclear area (NA) and variation of nuclear area (VA), in the entire
      epithelium and in three sublayers, parabasal, intermediate, and superficial. DNA
      aneuploidy was found in only half of the cases classified as 'high-grade' (HG)
      lesions, comprising carcinoma in situ (CIS) and severe epithelial dysplasias
      (EDIII), and was chiefly demonstrable in the parabasal third of the epithelium.
      The other lesions were DNA euploid. HG lesions showed highly significant
      increases of NA and VA at the lower levels of the epithelium when compared with
      'low-grade' (LG) lesions comprising moderate and mild epithelial dysplasias (EDII
      and EDI). Our data show that the combination of multiparameter image analysis
      with conventional morphology assists in the objective grading of precancerous
      lesions and permits the reliable detection of high-grade lesions.

PMID- 8568594
TI  - Multiple genetic alterations in malignant metastatic insulinomas.
AB  - Proto-oncogenes, growth factors/receptors, and tumour suppressor genes were
      analysed in malignant metastatic insulinomas. Normal pancreas showed only a
      moderate immunoreaction for c-myc proto-oncogene and a strong reaction for
      insulin. Benign insulinomas were slightly or moderately positive for transforming
      growth factor alpha (TGF alpha), weakly positive for epidermal growth factor
      receptor (EGF-R), and strongly positive for c-myc and insulin. In malignant
      insulinomas, besides a strong immunoreaction for c-myc and TGF alpha, activation
      of c-K-ras and overexpression of p53 protein were found. Insulin reaction was
      moderate or strong. Three out of six malignant insulinomas displayed a c-K-ras
      point mutation at codon 12. All mutations were guanine to cytosine transversion,
      resulting in amino acid substitution, glycine to arginine. Mutations were present
      in metastatic insulinomas only. Patients with mutated c-K-ras oncogene had
      overexpression of p53 protein as well as c-myc and TGF alpha overexpression. Our
      results support the view that malignant progression is a consequence of more than
      one genetic lesion and suggest that activation of myc, TGF alpha an ras genes
      plays a role in a multistep process of tumour progression, perhaps serving as an
      initiating event.

PMID- 8568595
TI  - Distribution of CD1a-positive Langerhans cells and lymphocyte subsets in
      transitional cell carcinoma of the urinary bladder. An immunohistological study
      on frozen sections.
AB  - The distribution of CD1a-positive Langerhans cells, CD4-positive T-helper cells,
      and CD8-positive T-suppressor cells in 36 patients with transitional cell
      carcinoma of the urinary bladder was studied immunohistochemically on frozen
      sections. Multiple tissue specimens from the tumour, the adjacent mucosa, and
      random bladder wall biopsies were examined. Langerhans cells were mainly
      interspersed among the tumour cells, whereas T-helper cells were present in
      aggregates in the stroma. T-suppressor cells were present both in aggregates in
      the stroma and among the tumour cells. There was a marginal relationship between
      the density of Langerhans cells and the density of T-helper/inducer cells and a
      good relationship with CD8-positive cells. There was no statistically significant
      difference in the population density of Langerhans cells associated with the
      various clinicopathological variables, including growth pattern, histological
      grade and stage, or patient's age and sex. On the contrary, a statistically
      significant difference was found in the CD1a/CD4 ratio among specimens of
      different grades. These results show that CD1a cell populations correlate with T
      cell populations in bladder cancer, suggesting that Langerhans cells take part in
      the immune response carried out by T lymphocytes, their task being apparently
      antigen presentation.

PMID- 8568596
TI  - Immunohistological localization of the novel epitope related to type IV collagen
      in normal and diseased renal tissues.
AB  - Type IV collagen is a major component of the renal glomerular extracellular
      matrix. A recently characterized monoclonal antibody, JK132, which was originally
      produced by immunization with human placental type IV collagen, recognizes a new
      epitope which is different from alpha 1-alpha 6 chains of type IV collagen. Using
      immunofluorescence and immunogold electron microscopy, the distribution of the
      epitope of JK132 has been compared with the distribution of alpha 1, alpha 2,
      alpha 3 and alpha 4 chains of type IV collagen in normal human kidney and in the
      renal tissues of patients with various types of glomerulonephritis. In normal
      human kidney, JK132 reacted with mesangial matrix, Bowman's capsular basement
      membrane (BCBM), tubular basement membrane, and vessel walls, but did not react
      with glomerular basement membrane (GBM). This distribution is different from the
      distribution of alpha 1-alpha 4(IV) chains. In IgA nephropathy and
      membranoproliferative glomerulonephritis, the staining intensity for JK132 was
      increased in expanded mesangial matrix. In glomeruli with severe mesangial
      proliferation, the epitope of JK132 extended to the endothelial side of the GBM.
      In membranous nephropathy, staining for JK132 was virtually unchanged from
      normal. This study suggests that the epitope of JK132 increases in amount during
      the process of mesangial proliferation and could serve as a marker for mesangial
      matrix expansion in glomerulonephritis.

PMID- 8568597
TI  - Pulmonary eosinophilia in sudden infant death syndrome.
AB  - A recent immunohistochemical study found increased numbers of eosinophils, but no
      mast cells, in the pulmonary parenchyma of infants who died of sudden infant
      death syndrome (SIDS). The present study tested the hypothesis that this
      pulmonary eosinophilia could be IgE-mediated. Histomorphometry was used to
      compare the numbers of eosinophils, mast cells, and IgG-, IgA-, IgM- and IgE
      expressing lymphoid cells in the lungs of two groups of infants. Twenty-eight
      subjects aged less than 1 year were selected from post-mortem records of infant
      deaths between 1989 and 1992. Fourteen were cases of SIDS and these infants were
      matched for age and gender to 14 controls who died of other non-pulmonary
      conditions. Immunohistochemical stains were used and positive cells were counted
      on six peribronchial and six subpleural fields. The numbers of eosinophils in
      both peribronchial and subpleural regions were significantly higher in SIDS
      compared with controls (P = 0.0071 and P = 0.041, respectively). The numbers of
      IgA-expressing lymphoid cells were also significantly increased in SIDS cases (P
      = 0.042). There were no differences in IgG, IgM or IgE expression or in mast cell
      numbers. These results confirmed that pulmonary eosinophils are increased in
      SIDS, but not through an IgE-mediated pathway.

PMID- 8568598
TI  - Transmural changes in mast cell density in rat heart after infarct induction in
      vivo.
AB  - The cardiac distribution of mast cells was investigated after the induction of
      acute myocardial infarction in the rat. The left anterior descending coronary
      artery (LAD) was occluded by ligation in the infarct group, whereas in sham rats
      only a superficial ligature was placed beside the LAD. Rats of both groups were
      killed at 4, 7, 14, 21, 35, and 85 days following surgery. Hearts were excised
      and formalin-fixed. Mast cell densities were monitored in subepicardial and
      subendocardial layers of the left ventricle (LV) in 6 microns thick toluidine
      blue-stained cross-sections. In control (non-operated) animals, mast cell
      densities were comparable in the LV subepicardial and subendocardial layers (1.5
      2.0 cells per mm2). Following infarction, the mast cell density at the
      subepicardial site of the infarction gradually increased, reaching a maximum of
      25 cells per mm2 on day 21, while a non-significant increase was observed at the
      subendocardial site. In the non-infarcted regions, the mast cell density
      increased transiently to reach a maximum of 7 cells per mm2 on day 35 in the
      subepicardial layer. Again, changes in mast cell density in the subendocardial
      layer were non-significant. In the sham group, a gradual increase to 9 cells per
      mm2 on day 21 and a subsequent decrease to 5 cells per mm2 on day 85 were
      observed in the subepicardial layers. These findings indicate a massive
      accumulation of mast cells in the subepicardial layers of the infarcted region
      and a small but significant effect of the surgical procedure on cardiac mast cell
      deposition, especially in the outer layers of the left ventricle.

PMID- 8568599
TI  - Angiotensin converting enzyme inhibition prevents polyploidization of
      cardiomyocytes in spontaneously hypertensive rats with left ventricular
      hypertrophy.
AB  - Polyploidization of cardiomyocyte nuclei is a physiological phenomenon that
      increases in pathological conditions such as myocardial hypertrophy. The purpose
      of this study was to evaluate the potential benefit of the angiotensin converting
      enzyme (ACE) inhibitor quinapril in reversing the polyploidization of
      cardiomyocyte nuclei in spontaneously hypertensive rats (SHR) with established
      left ventricular hypertrophy (LVH). Sixteen week-old male SHR were treated with
      oral quinapril (average dose 10 mg/kg per day) for 20 weeks. Sixteen- and 36-week
      old untreated SHR and 16- and 36-week-old normotensive Wistar-Kyoto (WKY) rats
      were used as controls. Nuclear polyploidization was determined by DNA flow
      cytometry of frozen tissues from the left ventricle, at least 20,000 nuclei being
      measured in each sample. The rates of tetraploidy in the 16- and 36-week-old SHR
      groups were 2.8 per cent (range 2.16-3 per cent) and 5.4 per cent (range 4.9-5.9
      per cent), respectively. Treated SHR had a similar rate of DNA tetraploidy to the
      16- and 36-week-old WKY rat groups: 1.8 per cent (range 1.5-2.3 per cent), 1.55
      per cent (range 1.5-1.6 per cent), and 1.5 per cent (range 1.4-1.6 per cent),
      respectively. The differences in the percentage of tetraploid cardiomyocytes
      between the SHR untreated groups and the SHR treated group were statistically
      significant (P < 0.05). Regression of LVH and normalization of blood pressure
      were observed in treated rats. These results indicate that DNA tetraploidy in the
      myocardium of SHR increases with hypertrophy and decreases on quinapril
      treatment. It is suggested that ACE inhibition modifies nuclear processes
      involved in myocyte growth in arterial hypertension.

PMID- 8568600
TI  - Re: Problems related to immunohistochemical detection of monotypic immunoglobulin
      light chain expression on B cells.

PMID- 8568601
TI  - Morphometry in pathology.

PMID- 8568602
TI  - Action spectroscopy in complex organisms: potentials and pitfalls in predicting
      the impact of increased environmental UVB.
AB  - Evaluating the effects of broad spectrum sources, including sunlight, on humans
      and their environment requires knowledge both of the effects of various
      wavelengths of radiation in those sources on biological systems and of the kinds
      and magnitude of changes in those sources. Action spectroscopy-the determination
      of the effect of radiation on an organism as a function of wavelength-provides a
      major method for evaluating the effects of a source, including that of changes in
      its intensity and wavelength distribution. Although action spectra for UV
      radiation damage to higher organisms can give useful information, inappropriate
      analyses can lead to misleading or even incorrect results. It is thus essential
      to consider carefully methods of analyzing action spectra and their consequences
      for evaluating the effects of changes in the solar spectrum.

PMID- 8568603
TI  - Biological dosimetry and action spectra.
AB  - In view of the current renewed interest in biological dosimeters, data obtained
      in the mid-1970s with the UV-sensitive Bacillus subtilis spore UVSSP both in
      natural sunlight in Rio de Janeiro and with defined monochromatic radiation is
      reproduced and reconsidered. The crucial issue of the correspondence of the
      wavelength dependence of the dosimeter response and the biological effect of
      interest is discussed with reference to end points such as cytotoxicity and
      melanoma and non-melanoma skin cancer induction. The necessity of taking into
      account UVA as well as UVB effects in the overall biological effectiveness of
      sunlight is evaluated and discussed. Gene activation is proposed as a basis for
      developing sensitive biological markers that can differentiate between UVA and
      UVB effects and also be used to determine UV penetration into target tissue.

PMID- 8568604
TI  - DNA UVB dosimeters.
AB  - DNA can be used to establish and monitor solar UVB dose. Since the principal
      molecular site of UVB damage in living organisms is DNA, it is logical to
      quantitate biologically effective solar UVB in DNA dosimeters. In addition to
      their particular sensitivity to UVB, DNA dosimeters have the advantage of a 2 pi
      geometry for collecting diffuse UVB radiation from all vectors, low cost, small
      size and portability, and no moving parts. Both molecular (cyclobutane pyrimidine
      dimers) and biological (bacteriophage plaques) dosimeters can be quantitated as
      endpoints to yield the total dose. DNA dosimeters integrate the absorbed energy
      of all UVB wavelengths (290-320 nm), are highly sensitive to the differential
      biological effectiveness of these wavelengths, and also integrate over time in
      hours, days or weeks of exposure. Our experiments have focused on the
      demonstration of DNA solar dosimeters in the ocean at various depths, the
      application of the dosimeters to the terrestrial monitoring of solar UVB under
      various conditions, and the development of a mini-dosimeter which uses nanograms
      of DNA and is assayed by polymerase chain reaction.

PMID- 8568605
TI  - UV radiation ocular exposure dosimetry.
AB  - There is currently some degree of controversy as to the magnitude of cataract and
      other ocular diseases related to human lifetime exposure to UV radiation (UVR).
      Concerns about the depletion of stratospheric ozone and the related increase in
      terrestrial UVR exposure have emphasized the importance of resolving this
      controversy. A careful study of ocular exposure to environmental sunlight
      demonstrates that it is not simple to determine accurately the level of solar UVR
      exposure of the human eye. Past attempts to measure or calculate UVR exposure of
      the eye have generally relied on the measurement of ambient UVR in sunlight with
      global monitors. Unfortunately, such attempts have seldom assessed properly the
      large role of ground reflection, the horizon sky contribution, the degree of lid
      opening and the extreme lateral component of UVR incident on the eye. A series of
      recent ocular dosimetry studies are described which have considered all of these
      factors. In addition, the value of different types of eye protection is shown to
      vary widely depending on the frame design. The dosimetry studies can be confirmed
      by a biological dosimeter--the human cornea. Because the action spectrum and
      threshold for human photokeratitis are well defined, the living cornea can serve
      as a biological dosimeter for ocular exposure.

PMID- 8568606
TI  - Experience with early amniocentesis.
AB  - Literature concerning early genetic amniocentesis, obtained before 14-15 weeks of
      gestation, has been examined and compared. Key figures of post-procedural
      spontaneous fetal losses have been compared as well as cytogenetic data from the
      published series. Cytogenetically more samples fail to grow in the early weeks,
      but the diagnostic accuracy seems to be comparable with that of amniocentesis
      obtained in the later weeks. A sampling method, improving the cell yield by means
      of filtration, has been developed in order to lower the risk of culture failure
      and reduce the reporting time in the gestational weeks 11 to 13. The filter
      technique is under evaluation in a randomized trial. Detection of neural tube
      defects with early amniotic fluid sampling is possible, but whether the detection
      rate is comparable to that of standard amniocentesis remains to be seen. Although
      the safety of early amniocentesis has not yet been evaluated in a randomised
      study, data from almost 5,000 cases suggest that the procedure related loss rate
      is approximately 1%, and thus the same as for standard amniocentesis and
      chorionic villus sampling.

PMID- 8568607
TI  - Motor responsivity during habituation testing of normal human fetuses.
AB  - Features of fetal motor responsivity include both the magnitude of the startle
      response elicited by a single stimulus (i.e., basal reactivity) and the ease by
      which responding to successive stimuli is inhibited (i.e., habituation). We
      examined basal motor reactivity and habituation of the motor response in 56
      normal human fetuses between 34 and 40 weeks of gestation. Testing consisted of 8
      trials of a 1-sec vibroacoustic stimulus (VAS) with a 10-sec interstimulus
      interval. A score of 0-10 was assigned for each trial based on subjective
      assessment of intensity and duration of the fetal motor response. Measures of
      habituation included the ratio of responding after a fixed number of trials
      divided by the initial response, and the rate of change in the behavioral
      response over trials. No relationship was found between the rate of motor
      habituation and either basal reactivity, gestational age, or prestimulus fetal
      heart rate (FHR) variability. In contrast, more mature fetuses responded less
      intensely to the first stimulus than did their younger counterparts (r = -0.329,
      p = 0.005), and fetuses who were initially in a quiet state exhibited a more
      vigorous startle response as compared to fetuses who were initially in a more
      active state (r = -0.372, p = 0.001). The relationship between basal reactivity
      and prestimulus FHR variability was statistically significant even after
      controlling for gestational age (r = 0.295, p = 0.01). These findings may have
      important clinical implications regarding the appearance in early life of certain
      behavioral tendencies such as temperament.

PMID- 8568608
TI  - Concentration of purine compounds in the cerebrospinal fluid of infants suffering
      from sepsis, convulsions and hydrocephalus.
AB  - Catabolites of purine nucleotides were measured in the cerebrospinal fluid (CSF)
      of newborn infants with sepsis, seizures and hydrocephalus using isocratic
      reversed-phase HPLC. The inosine levels in the CSF of the infants with any of the
      illnesses were significantly higher when compared with the controls. There was a
      tendency for hypoxanthine levels to be higher in the group of children with
      hydrocephalus. No significant differences in the concentrations of xanthine,
      adenine and uric acid were found. The inosine concentration in the CSF is
      proposed to be a more sensitive indicator of brain injury than the levels of
      other CSF purines. The levels of all purine metabolites measured in the CSF
      showed large individual variations. The ratio between hypoxanthine (as an
      indicator of ATP breakdown) and uric acid (as a scavenger of oxygen free
      radicals) concentration is proposed as a new criterion to be used in the
      evaluation of brain injury.

PMID- 8568609
TI  - Early neonatal complications after elective preterm delivery in hypertensive
      pregnancies.
AB  - We evaluated the rates of short-term neonatal complications, neonatal brain
      damage or mortality in a group of 96 singleton pregnancies complicated by
      hypertension and electively delivered before 36 weeks gestation. The neonatal
      outcome of these pregnancies was compared with that of a matched control group of
      192 uneventful pregnancies delivered because of spontaneous preterm labor or
      premature rupture of membranes. Although the rates of acidosis, apneoic crises,
      bradycardia and ventilatory support were higher among cases than controls, the
      risk of intraventricular hemorrhage, severe brain damage (grade III-IV
      intraventricular hemorrhage or periventricular leucomalacia) or neonatal
      mortality were comparable between the two groups. Neonatal complications were
      more frequent among infants born to mothers with severe hypertension or severe
      proteinuria. In conclusion, this study has shown that short term neonatal
      complications after elective preterm delivery in hypertensive pregnancies are
      increased in comparison with low risk controls. However, these complications,
      which were well managed in our intensive care nursery, did not affected neonatal
      mortality or severe brain damage.

PMID- 8568610
TI  - The outcome of post-term pregnancy. A comparative study.
AB  - The aim of this study was to evaluate whether prolonged pregnancy was associated
      with dangers to the fetus, and to assess the incidence of cesarean section as
      well as fetal distress. The outcome for mother and baby in both groups of
      patients with post-term pregnancies was generally good. Furthermore, the
      improvement of prognosis for postdate pregnancy is due to the availability of
      electronic fetal monitoring and ultrasound, making possible the identification of
      fetal distress, as well as the use of prostaglandin to ripen a stubborn cervix,
      and induce labor successfully in most cases. Consequently, we feel that fetal
      jeopardy with continued intrauterine existence, as well as the excellent results
      of induction of labor, justify the active approach. The routine induction of
      labor in postdate pregnancy may reduce perinatal morbidity, as indicated in
      previous reports [2], and confirmed in this study.

PMID- 8568611
TI  - Pregnancy, immunosuppression and reactivation of latent toxoplasmosis.
AB  - Toxoplasmosis is a chronic, latent infection which can be reactivated in the
      presence of immunosuppression. The critical question in obstetrics is whether
      toxoplasmosis may be reactivated in the presence of the physiological
      "immunosuppression" of pregnancy. Standard in vitro tests, done in 24 healthy
      pregnant women and compared with the literature, show no significant changes in
      humoral and cellular immunity during pregnancy. However, the fact that some
      infections occur more frequently and more severely than in non-pregnant women
      (e.g. those due to cytomegalovirus (CMV) and human papilloma virus (HPV) points
      to a degree of pregnancy-associated immunosuppression. Non-rejection of the
      semiallogenic fetus is achieved in presence of maternal immunocompetence and is
      explained mainly by local changes in immune function, mediated by inhibitors of
      decidual, placental and fetal origin, and by the absence of class II
      histocompatibility antigens at the fetomaternal interface. Immune status allowing
      reactivation of toxoplasmosis was studied in a selected group of (predominantly
      male) AIDS patients from the Swiss HIV Cohort study. Shortly before (cerebral)
      reactivation of toxoplasmosis, 92% of these patients had very low CD4 lymphocyte
      counts (mean 50 cells/microliters, i.e. lower than ever recorded in a normal
      uncomplicated pregnancy). In a larger population of 48 women receiving
      immunosuppressive therapy after organ transplantation, not a single case of
      cerebral toxoplasmosis was observed during pregnancy, while in the 105 HIV
      positive women in the Swiss HIV and Pregnancy study, there was only one case of
      cerebral toxoplasmosis during pregnancy and the puerperium (20 CD4/microliters),
      even though some 17% of those sampled (18/105) had CD4 levels below 200
      cells/microliters on at least one occasion during pregnancy. These findings
      explain why latent toxoplasmosis is not reactivated in normal pregnancy, and why
      it is only likely in an immunosuppressed mother when her CD4 lymphocyte count is
      very low (< 200 cells/microliters). In such cases, a prophylactic treatment to
      prevent maternal reactivation and vertical transmission of toxoplasmosis may be
      useful.

PMID- 8568612
TI  - Gene linkage analysis and DNA based detection of autosomal dominant polycystic
      kidney disease (ADPKD) in a newborn infant. Case report.
AB  - Bilateral polycystic kidneys were detected by ultrasound at 23 weeks gestation in
      a male fetus. Bilateral renal cysts were subsequently also found in the
      asymptomatic propositus' mother and grandmother, suggesting the diagnosis of
      autosomal dominant polycystic kidney disease (ADPKD). The renal ultrasonograms
      showed cortical cysts with normal or decreased-sized kidneys. Renal function was
      normal. Seven available members of the family were genotyped for flanking DNA
      markers tightly linked to the PKD1 gene on chromosome 16p, and for a polymorphism
      close to a second putative disease gene (PKD2) on chromosome 2. The genetic
      linkage approach allowed us to detect with a high degree of accuracy the ADPKD1
      at risk chromosome in the three patients, as well as in a 28-year-old unaffected
      female. This report illustrates the feasibility and the usefulness of recent
      molecular genetic strategies for diagnostic purposes in ADPKD, especially when
      clinical and radiological data are atypical. Furthermore, it also confirms that
      early or very early onset forms of the disease are not uncommon, and should be
      considered in the differential diagnosis of childhood cystic disease.

PMID- 8568613
TI  - Three-dimensional ultrasonography in prenatal diagnosis.
AB  - Within the past five years, 3D ultrasonography has developed to the degree that
      it offers both the patient and the examiner an entirely new visual experience in
      prenatal diagnosis. With the system described here (Kretz-technik, Austria), any
      desired plane can be displayed within the stored volume, and within seconds a
      high-quality 3D surface or transparent image can be calculated and displayed on
      the ultrasound monitor without need for an external workstation. All of this can
      be performed routinely in the clinical setting. Since 1989 we have routinely
      examined a total of 458 fetuses (242 normal and 216 with anomalies) between 16
      and 38 weeks of gestation, supplementing our conventional 2D ultrasound scans
      with a 3D examination using an abdominal volume transducer. A comparison of the
      2D and 3D techniques shows that 3D provides a diagnostic gain in a large
      percentage of cases (64.2%). The simplest 3D technique of the orthogonal image
      display provided a diagnostic gain in 46.2% (61/132) of the cases owing to the
      accurate topographic depiction of the desired image plane. The combined 3D
      display (orthogonal format plus a 3D surface or transparent view) provided a
      diagnostic gain in 71.5% (233/326) of the cases. This higher percentage resulted
      from the additional 3D surface reconstruction, the ability to view and evaluate
      the fetus from various angles, the ability to determine the exact size of a fetal
      defect, the depiction of skeletal anatomy in the transparent mode, and the
      improved delineation of complex malformations. Problems with 3D imaging are
      encountered in patients with pronounced oligohydramnios, which prevents surface
      reconstruction, and in the examination of moving objects, which produce motion
      artifacts.

PMID- 8568614
TI  - Parenteral nutrition infused by epicutaneous catheter: pulmonary complication.
AB  - We present three preterm infants with pulmonary complications due to central
      venous silicone catheters malpositioned in the left or right pulmonary artery.
      One infant developed an arterial-bronchial fistula. The other two infants had
      pneumonitis without evidence of vessel perforation. The course of these
      complications was good after the catheter was withdrawn into the superior vena
      cava.

PMID- 8568615
TI  - Intra-amniotic maternal hemorrhage in preterm labor: a case report.
AB  - A primigravid women was transferred to hospital because of preterm labor at 32
      weeks' gestation with no vaginal bleeding. Hematologic studies showed severe
      anemia. Ultrasound examination revealed polyhydramnios and a clot around the
      umbilical cord without retroplacental hematoma. Diagnostic amniocentesis revealed
      heavily blood stained fluid, but HbF was not detected. With a clinical diagnosis
      of intra-amniotic maternal hemorrhage, immediate cesarean section was performed.
      The mechanism of intra-amniotic maternal hemorrhage is discussed.

PMID- 8568616
TI  - Good fetal outcome following prolonged indomethacin induced anhydramnios. Case
      report.
AB  - Indomethacin is a non steroidal anti-inflammatory agent widely employed in the
      treatment of premature contractions. Indomethycin induced oligohydramnios is a
      well described side-effect, and is considered an indication for treatment
      discontinuation. We present a case of prolonged anhydramnios, secondary to
      indomethacin therapy with no apparent ill-effect on the fetus or neonate.

PMID- 8568617
TI  - Amniotic fluid levels of CA 19.9 and CA 15.3 in normal and Down's syndrome
      pregnancies.
AB  - CA 125, CA 19.9 and CA 15.3 are antigenic determinants on glycoproteins commonly
      used as serum markers in gynecologic oncology. CA 125 was also investigated in
      the amniotic compartment of Down's syndrome pregnancies. The objective of this
      study was to evaluate the concentration of CA 19.9 and CA 15.3 in the amniotic
      fluid of normal and Down pregnancies. The concentration of these antigens was
      measured in stored amniotic fluid samples from 15-19 weeks pregnancies with and
      without Down's syndrome fetuses and expressed in multiples of the median for
      normal pregnancies of the same gestational age. The study group included 20
      samples selected from single Down's syndrome pregnancies. Each of these samples
      were matched with three control samples from unaffected pregnancies, matched for
      maternal age, gestational age and duration of storage of the sample. The median
      MoM values of CA 19.9 and CA 15.3 in Down's syndrome pregnancies were
      respectively 1.11 MoM and 1.16 MoM, not significantly different from those of
      unaffected pregnancies (CA 19.9: 1.02 MoM; CA 15.3: 0.99 MoM). In the present
      study we have not found significantly different levels of CA 19.9 and CA 15.3 in
      the amniotic fluid of fetuses affected by Down's syndrome and in the controls.

PMID- 8568618
TI  - Compression of lactose, glucose and mannitol granules.
AB  - The effect of the amount of granulation liquid, compression speed and maximum
      compression force on then compressibility and compactibility of lactose, glucose
      and mannitol granules was studied. The porosity based on the geometrical shape
      and the uniformity of weight of tablets was also studied. Lactose and mannitol
      granules showed a greater compressibility than glucose granules. Mannitol
      granules produced the hardest tablets and lactose and glucose the weakest. The
      change in the amount of granulation liquid caused changes both in the granule
      porosity and in the amount of binder; this was attributed to differences in
      tablet strength. All parameters studied were relatively insensitive to changing
      speeds of compression in the range used, except for the breaking force of
      mannitol tablets, which was greatest with the lowest speed of compression. All
      granule masses showed a relatively good continuous flow suitable for table
      production. Tablets compressed from lactose granules had the best uniformity of
      weight of the tablets studied.

PMID- 8568619
TI  - Enthalpy and entropy contributions to the solubility of sulphamethoxypyridazine
      in solvent mixtures showing two solubility maxima.
AB  - The solubility of sulphamethoxypyridazine was measured at several temperatures in
      mixtures of water:ethanol and ethanol:ethyl acetate. Sulphamethoxypyridazine was
      chosen as a model drug to compare the solvation effects of proton donor-proton
      acceptor (water and ethanol) and proton acceptor (ethyl acetate) solvents and
      mixtures of these solvents because this drug contains functional groups capable
      of Lewis acid-base interaction. A plot of the mole fraction solubility against
      the solubility parameter (delta 1 = 30.87 MPa1/2 (20:80 v/v water:ethanol) and
      another at delta 1 = 20.88 MPa1/2 (30:70 v/v ethanol:ethyl acetate) at all the
      temperatures under study. The enthalpies and entropies of mixing as well as the
      enthalpies and entropies of transfer of sulphamethoxypyridazine from ethanol of
      mixing as well as the enthalpies and entropies of transfer of
      sulphamethoxypyridazine from ethanol to water:ethanol and ethanol:ethyl acetate
      mixtures were calculated to compare solvation characteristics of the solvent
      mixtures toward the drug. As ethanol is added to water, the entropy increases and
      the structure of the solvent mixture became less ordered, favouring the
      interaction of the drug with the solvent mixture. On the other hand, in the case
      of the ethanol:ethyl acetate mixture, solubility is favoured by the more negative
      enthalpy values. This way, the same result, i.e. a solubility maximum, is
      obtained by different routes. In the ethanol:water mixtures, the dissolution
      process if entropy-controlled while enthalpy is the driving force in the case of
      ethanol:ethyl acetate mixtures. The two solvent systems show enthalpy-entropy
      compensation. Water deviates from the linear relationship due possibly to its
      hydrophobic effect.

PMID- 8568620
TI  - Particle size studies for subcutaneous delivery of poly(lactide-co-glycolide)
      microspheres containing ovalbumin as vaccine formulation.
AB  - The primary objectives of the present study were to produce poly(lactide-co
      glycolide) (PLGA) microspheres with different diameters, to characterize these
      microspheres which were loaded with a model antigen, ovalbumin and to evaluate
      the effect of microsphere particle size on the serum antibody levels following
      administration to mice. Four kinds of ovalbumin-loaded PLGA microspheres with
      different diameters (1.2, 3.5, 7.0 and 14.3 microns as mean volume diameter) were
      manufactured by a w/o/w emulsion/solvent evaporation method. Low loading percent
      (0.08%-0.25% w/w) and efficiencies (8-25% w/w) were observed. Examination using
      scanning electron photomicrographs showed smooth spherical particles. The in
      vitro release of ovalbumin from microspheres showed an expected burst release
      with all batches and the extent of the burst release increased with decreasing
      diameters of spheres; PLGA microspheres with the smallest diameter (1.2 microns)
      showed an 80% burst release within one day. Approximately 10-60% of ovalbumin
      remained unreleased 30 days later. The single subcutaneous administrations of
      ovalbumin-loaded PLGA microspheres with different diameters to mice induced good
      antibody responses above ovalbumin saline negative controls at 3, 6, 9, and 12
      weeks after inoculation. Especially, 0.16% ovalbumin-loaded PLGA microspheres
      having mean volume diameter of 3.5 microns exhibited the best immune responses
      with values greater than those obtained after inoculation with adjuvants such as
      complete Freund's adjuvant or alum as positive control. The strong adjuvant
      activity of PLGA microspheres as vaccine formulation was suggested.

PMID- 8568621
TI  - The transfer of polystyrene microspheres from the gastrointestinal tract to the
      circulation after oral administration in the rat.
AB  - Factors relating to the transfer of latex microspheres of 0.87 micron mean
      diameter from the gastrointestinal tract (GIT) to the circulation have been
      investigated. The rapidity of appearance and the number of particles increased
      when the volume of water used as a suspending vehicle was increased. This was
      probably due to barrier cell integrity being compromised so that the movement of
      particles across the enterocytes would be enhanced. Particles were swept into
      these channels by the waterflow. The tonicity of the fluid was important as
      isotonic and hypertonic saline were not as effective as water in transferring
      particles. Particles were transferred from GIT segments adjacent to the stomach
      which may in part explain the rapid appearance of particles in the circulation.
      Particle uptake was blocked by cytochalasin B which suggests an active component
      may also be involved.

PMID- 8568622
TI  - The effect of lysine, a water-structure breaker, on the stability of phospholipid
      stabilized emulsions.
AB  - Phospholipid-stabilized emulsion properties were studied in the presence of
      lysine, a water-structure breaker, using two unrelated procedures, photon
      correlation spectroscopy and a light obscuration instrument. Commercial
      Intralipid was used as a control. Lysine 0.125, 0.25 and 0.5 M induced changes in
      the size distribution of a non-heated model emulsion system, irrespective of any
      changes produced by environmental pH. Some of the laboratory-prepared emulsions
      containing lysine were more stable than the corresponding commercial heat
      sterilized product Intralipid, once heated. The results suggest that lysine is
      producing an effect on the nascent oil-water interface that controls the physical
      stability of the system. Once the heat-induced interfacial rearrangement of the
      individual phospholipid molecules occurs, the influence of lysine becomes
      diminished.

PMID- 8568623
TI  - Bioavailability and pharmacokinetics of sublingual oxytocin in male volunteers.
AB  - The aim of this investigation was to assess the bioavailability and
      pharmacokinetics of oxytocin in six male subjects after a sublingual dose of 400
      int. units (684 micrograms) and after an intravenous dose of 1 int. unit (1.71
      micrograms). After intravenous administration, the pharmacokinetic profile could
      be described with a two-compartment model. The distribution half-life was 0.049
      +/- 0.106 h, the elimination half-life was 0.33 +/- 0.23 h, the total body
      clearance was 67.1 +/- 13.4 L h-1 and the volume of distribution was 33.2 +/-
      28.1 L. After sublingual administration, a poor bioavailability with a 10-fold
      variation between 0.007 and 0.07% was observed. The pharmacokinetic profile could
      be described with a one-compartment model. The lag time was subject-dependent and
      ranged between 0.12 and 0.30 h (40% CV). The absorption half-life was 0.45 +/-
      0.29 h, and the apparent elimination half-life 0.69 +/ - 0.26 h. This study
      showed a very poor and interindividual variability in bioavailability. The
      sublingual route of administration with its 'long' lag time and 'long' absorption
      half-life would not seem a reliable route for accurate high dosing for immediate
      prevention of post-partum haemorrhage.

PMID- 8568624
TI  - Effects of ageing on the oral absorption of D-xylose in rats: analysis of
      gastrointestinal disposition.
AB  - The effects of ageing on the oral (gastrointestinal) absorption of D-xylose were
      investigated by analysing the gastrointestinal disposition after oral
      administration to young (9 weeks) and old (53 weeks) rats. A linear model
      assuming first-order gastric emptying followed by first-order intestinal
      absorption was fitted to remaining fraction vs time profiles for the stomach and
      small intestine to estimate the gastric emptying rate constant (kg) and the
      intestinal absorption rate constant (ka). In young and old rats, Kg values were
      0.087 +/- 0.008 and 0.070 +/- 0.007 min-1, respectively, and ka values were 0.020
      +/- 0.002 and 0.018 +/- 0.002 min-1, suggesting an insignificant effect on ageing
      on the rate of oral absorption. The average intestinal lumen volume (Vav) was
      unchanged with ageing, and so was the apparent intestinal membrane permeability
      clearance (CLapp) as the product of Ka and Vav. However, the small intestinal
      transit time (Tsi) was suggested to be twice that in older rats (171 min) than in
      young rats (78 min) by the analysis of gastrointestinal disposition of inulin, a
      non-absorbable marker. It was also shown that our preceding finding of an
      increase in the fraction absorbed of D-xylose with ageing can be solely
      ascribable to the delay in intestinal transit. Thus, among various determinants
      of oral absorption, only Tsi was found to be altered with ageing. The CLa,app and
      ka of passively absorbed drugs such as D-xylose may be generally unchanged, and
      the fraction absorbed may increase with ageing by the delay in intestinal
      transit.

PMID- 8568625
TI  - Precorneal clearance of mucoadhesive microspheres from the rabbit eye.
AB  - The ocular disposition of hydrated 111In-labelled microspheres was investigated
      in the rabbit by gamma scintigraphy. Microspheres of cross-linked poly(acrylic
      acid) (Carbopol 907) were prepared by a w/o emulsification process. An in-vitro
      mucoadhesion test of prehydrated microspheres showed that greater adhesion was
      achieved to a mucus gel at pH 5.0 compared with pH 7.4. Clearance was a biphasic
      process with a rapid initial phase preceding a slower basal phase. When hydrated
      in pH 5.0 phosphate buffered saline, clearance during the basal phase was slowed
      compared with a pH 7.4 buffered preparation. Both prehydrated preparations were
      retained on the preocular area during the basal phase for longer periods than non
      hydrated microspheres. The retention on the ocular surface of approximately 25%
      of the instilled dose would suggest this technology will have application for
      controlled ophthalmic drug delivery.

PMID- 8568626
TI  - Effect of oleanolic acid on complement in adjuvant- and carrageenan-induced
      inflammation in rats.
AB  - The present work was aimed at evaluating the influence of oleanolic acid on
      complement-related inflammation. In adjuvant-induced arthritis and carrageenan
      induced paw oedema in rats, oleanolic acid was found to possess significant anti
      inflammatory and complement-inhibitory activities. The intraperitoneal injection
      of oleanolic acid (60 mg kg-1, twice a day), before and after Freund's Complete
      Adjuvant challenge and thereafter repeated for several days, significantly
      reduced foot-pad thickness of experimental animal models and simultaneously
      reduced complement activity. Oleanolic acid also produced marked reduction in
      complement levels and inflammatory effects on carrageenan-induced paw oedema in
      rats when injected intraperitoneally (60 mg kg-1, twice a day).

PMID- 8568627
TI  - Synthesis and antiplatelet effects of omega-aminoalkoxylxanthones.
AB  - A series of omega-aminoalkoxylxanthones were synthesized and tested in-vitro for
      their ability to inhibit aggregation of rabbit washed platelets and human
      platelet-rich plasma (PRP) induced by various inducers. Nine of these compounds
      showed more potent antiplatelet effects than natural norathyriol tetraacetate on
      collagen-induced aggregation. The various omega-aminoalkoxyl side chains of the
      synthesized compounds modified the antiplatelet effects. All the compounds tested
      in human PRP showed significant inhibition of secondary aggregation induced by
      adrenaline, suggesting that the antiplatelet effects of these compounds is mainly
      due to an inhibitory effect on thromboxane formation. These compounds at high
      concentration also cause vasorelaxing action in rat thoracic aorta.

PMID- 8568628
TI  - Accumulation of 5-ethyl-2'-deoxyuridine and its 5,6-dihydro prodrugs in murine
      lung and its potential clinical application.
AB  - The accumulation of 5-ethyl-2'-deoxyuridine (EDU), (--)-trans-(5S,6S)-5-bromo-5
      ethyl-6-methoxy-5,6- dihydro-2'-deoxyuridine [(5S,6S)-BMEDU], (+)-trans-(5R,6R) 
      5-bromo-ethyl-6-methoxy-5,6-dihydro- 2'-deoxyuridine [(5R,6R)-BMEDU], (+)-trans
      (5R,6R)-5-bromo- 5-ethyl-6-ethoxy-5,6-dihydro-2'-deoxy- uridine (BEEDU), (+)
      trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy -5,6-dihydro-5'-O-valeryl-2'deoxyuridine
      (VBEEDU) [formula: see text] and (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5, 6
      dihydro-3'-5'-di-O-valeryl-2'-deoxyuridine [formula: see text] (DVBEEDU) in lung
      and other tissues was investigated in male Balb-C mice following intravenous
      injection of the corresponding 4-(14)C-labelled compounds. EDU showed a rapid
      distribution into liver and lung immediately after injection, and the overall
      levels of radioactivity in blood, liver and lung were similar. The distribution
      of radioactivity in lung after injection of [4-(14)C](5S,6S)-BMEDU and [4
      (14)C]5R,6R)-BMEDU were substantially different from one another and also from
      that of[4(-14)C]EDU. The radioactivity level present in lung samples after
      injection of both (4-(14C](5S,6S)-BMEDU and [4-(14)C](5R,6R)-BMEDU was
      substantially higher than that in blood samples. Radioactivity levels present in
      lung samples taken at 18 min after injection of [4-(14)C]BEEDU were significantly
      higher (P < 0.05) than those for liver and blood samples. Although the
      radioactivity present in lung samples after injection of [4-(14)C]BEEDU did not
      provide a higher radioactivity level in lung samples than did [4
      (14)C]BEEDU.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8568629
TI  - Inotropic and chronotropic effects of 4-(4'-n-butylaniline)-7,8- dimethoxy-5H
      pyrimido[5,4-b]indole in guinea-pig atria.
AB  - Cardiotonic effect of 4-(4'-n-butylaniline)-7,8-dimethoxy- 5H-pyrimido[5,4
      b]indole (B11) was investigated in isolated cardiac tissue preparations. The
      action of this agent on force of contraction, beating frequency and cyclic
      nucleotide phosphodiesterase (PDE) activity was studied. Amrinone was used for
      comparison. B11 produced concentration-dependent (5 x 10(6)-1 x 10(-4)M) positive
      inotropic and positive chronotropic responses in guinea-pig atrial tissues. The
      potency of B11 was greater than that of amrinone. The cardiotonic effects of B11
      were not modified by beta-adrenoceptor blockade. Carbachol inhibited the positive
      inotropic effect of B11. The activity of B11 was increased in desensitized left
      atrial tissues. B11 inhibited the activities of PDE isoenzymes (type I, II, IV
      and V) from dog heart ventricle and PDE type IV from guinea-pig heart ventricle
      nonselectively. It is concluded that B11 possesses potent positive inotropic
      activity in guinea-pig atria, and the effect is probably mediated by a non
      selective inhibition of PDE activity.

PMID- 8568630
TI  - Antiarrhythmic and electrophysiological effects in-vivo of the major metabolite
      of Org 7797 found in canine and rodent liver homogenate preparations.
AB  - Org 20781, the major metabolite of Org 7797 found in in-vitro experiments was
      examined for antiarrhythmic and electrophysiological effects in-vivo. Org 20781
      (0.5-2.0mg kg-1, i.v.) inhibited the development of early ischaemia-induced
      arrhythmias in rats, suppressed spontaneous ventricular tachycardia (VT) in
      conscious dogs with 24-h old infarcts, and prevented electrical induction of VT
      in dogs with 5-6 day old infarcts, actions associated with slowing of conduction
      at all levels of the myocardium. Cardiac refractory periods were only modestly
      prolonged whilst repolarization was unchanged. Peak plasma levels of the parent
      compound (infused to total doses of 2-4 mg kg-1) associated with suppression of
      late arrhythmias were 6-18 microM, whilst the mean plasma elimination half-life
      (in normal dogs) was 107 min. It was concluded that the major metabolite has a
      similar antiarrhythmic and electrophysiological profile to the parent compound,
      is at least half as potent and may contribute to the therapeutic effects of Org
      7797 administration.

PMID- 8568631
TI  - Effects of ginsenosides on vasodilator nerve actions in the rat perfused
      mesentery are mediated by nitric oxide.
AB  - This study was designed to explore the effect of ginsenosides, saponins from
      Panax ginseng, on the vasodilator nerve actions in the rat perfused mesentery and
      the mechanism of this effect. In the rat perfusion mesentery, when adrenergic
      nerves were blocked by guanethidine (5 x 10(-6) M) and vascular muscle tone was
      increased with methoxamine (5 x 10(-6)-10(-5) M), transmural field stimulation
      produced a frequency-dependent vasodilator response, which is due to the release
      of calcitonin gene-related peptide; ginsenosides significantly suppressed this
      vasodilator response in a concentration-dependent manner (3-30 micrograms mL-1).
      After pretreatment with saponin (50 micrograms mL-1, 3 min) to damage endothelial
      cells, this suppressing effect of ginsenosides was unaltered. However, the effect
      was abolished by N omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) M), an
      inhibitor of nitric oxide synthesis and addition of L-arginine (3 x 10(-4) M)
      restored this suppressing effect. Methylene blue (10(-5) M), an inhibitor of
      guanylate cyclase, also abolished the suppressing effect of ginsenosides.
      However, ginsenosides did not alter the relaxation responses caused by exogenous
      calcitonin gene-related peptide administration. We conclude that ginsenosides can
      produce an inhibitory effect on the vasodilator response prejunctionally in the
      rat perfused mesentery and that this effect of ginsenosides may be mediated by
      nitric oxide released from non-adrenergic, non-cholinergic nerves.

PMID- 8568632
TI  - 5-HT3 receptor-independent inhibition of the depolarization-induced 86Rb efflux
      from human neuroblastoma cells, TE671, by ondansetron.
AB  - The 5-HT3-receptor antagonist, ondansetron, has been shown to have positive
      effects in selected in-vivo models of memory impairment and anxiety. The exact
      mechanisms underlying such bioactivities are unknown. In the present work, an
      86Rb efflux bioassay was used to show that ondansetron has a unique ability to
      block voltage-gated potassium channels in TE671 human neuroblastoma cells. This
      intrinsic potassium-channel-blocking (KCB) property is relatively weak (IC50 20
      microM), but is not shared by other 5-HT3-receptor ligands including zatosetron,
      MDL 72222, LY 278, 584, zacopride, 1-phenylbiguanide, and ICS 205-930
      (tropisetron). Pre-incubation of the target neuroblastoma cells with several 5-HT
      receptor ligands including 5-hydroxytryptamine, 8-OH-DPAT, ketanserin, 2-methyl-5
      HT, as well as a number of potent 5-HT3 agonists and antagonists and two
      selective neurotoxins, failed to abolish the KCB action of ondansetron. A
      preliminary structure-activity relationship analysis indicates that the KCB
      activity of ondansetron is almost entirely attributable to its structural
      nucleus, 2,3-dihyro-9-methyl-4(1H)-carbazolone. It is hypothesized that the KCB
      action of ondansetron is mediated through receptors other than 5-HT3 receptors.
      The KCB activity of ondansetron may be a significant factor in the in-vivo
      cognition-enhancing activities of this compound, conceivably due to
      depolarization of the hippocampal synaptic membranes and a consequent
      augmentation of neurotransmission.

PMID- 8568633
TI  - [Studies on development of pharmaceutical preparation with the purpose of
      improving controlled-release and bioavailability].
AB  - During the past fifteen years, the experiments based on three main propositions
      were proceeded to carry out in our laboratory, that is, (1) Microencapsulation:
      The method of solvent evaporation in water or oily phases was adopted because of
      its comparative simplicity in the procedure and its high reproducibility. The
      application of pharmacokinetic consideration to in vivo evaluation of
      microencapsulated drugs using beagle dogs intended for obtaining controlled
      release by oral administration. The pullulan acetate phthalate microcapsules
      containing cefadroxil were prepared by the solvent evaporation method in liquid
      paraffin and showed a zero-order dissolution pattern in pH 6-7.4. (2) Rectal gel
      preparation: The hydrogels and xerogels were prepared by Eudispert hv. These gels
      have excellent staying properties in the lower part of the rectum, over a fairly
      long period. Eudispert hv hydrogels or xerogels containing propentfylline were
      tested for avoidance of the first-pass metabolism. The absolute bioavailability
      of propentofylline from gel preparations was almost 100%. (3) Binary vehicle for
      transdermal delivery: The effects of glycerides, short-chain alcohols and their
      binary vehicles as donor components on the skin permeation of ketoprofen across
      the excised hairless mouse skin were evaluated with the diffusion cell. Among
      single vehicles, Panasate 800 as lipophilic vehicle and ethanol as hydrophilic
      vehicle showed the effective permeation flux of ketoprofen. The greatest
      enhancement was observed in an ethanol/Panasate 800 (40/60) binary vehicle. The
      relationship between lipophilicity and skin permeability of 16 drugs from the
      ethanol/Panasate 800 (40/60) binary vehicle showed a parabolic shape with a peak
      at a more hydrophilic range compared with other past references.

PMID- 8568634
TI  - [Biosynthesis and microbial transformation of griseofulvin and carcinogenesis and
      prevention of cancer by estrogens].
AB  - In the biosynthetic study of griseofulvin by Penicillium urticae and microbial
      transformation of (-)- and (+)-dehydrogriseofulvin and their derivatives by
      Streptomyces cinereocrocatus excellent informations were obtained from 2H-NMR
      spectroscopy. In the reduction of (-)-dehydrogriseofulvin into (+)-griseofulvin
      by a partially purified enzyme system of S. cinereocrocatus, the origin of the 6'
      alpha-hydrogen of (+)-griseofulvin was a hydride ion donated by pro-4R-hydrogen
      of NADPH. In connection with the study of carcinogenesis, diethylstilbestrol
      (DES) was proved to disrupt microtubules in vitro. The other synthetic estrogens,
      E,E-dienestrol, meso-hexestrol, and dl-hexestrol were inhibitors of microtubule
      assembly in vitro, and induced twisted ribbon structures or ribbon-sheet
      microtubules from microtubule proteins. Next, the effects of DES and its methyl
      ethers on the chromosome of and the cellular microtubule architecture, revealed
      by fluorescent anti-tubulin antibody, of Chinese hamster V79 cells were examined,
      and further estradiol-17 beta was proved to exhibit higher microtubule-disruptive
      activity than DES in V79 cells. Furthermore, cytoplasmic microtubules in the
      human breast cancer cell lines MCF-7 and MDA-MB-231, estrogen receptor-positive
      and -negative cell lines, respectively, were disrupted equally by estradiol-17
      beta. Then, natural estrogens and their derivatives comprising 30 compounds in
      total were tested in Chinese hamster V79 cells, proving that 2-methoxyestradiol
      showed the strongest activity (EC50: 2 microM) to disrupt microtubules. Further,
      in the assay of indenestrol A, a metabolite of DES, indenestrol B and their
      monomethyl ethers, the 4'-methyl ether of [(-)-3S]-indenestrol B exhibited both
      the strongest cytotoxicity in, and greatest disruption of the cellular
      microtubules of V79 cells, and no correlation with the affinity for estrogen
      receptors was shown.

PMID- 8568635
TI  - [Uses of hydroxamic acids and of N-alkoxyimidoyl halides in organic synthesis].
AB  - Although N-hydroxyamides (1) have been known for over a century, the chemistry of
      1 is still relatively unexplored. The scope of the present review is a survey of
      the recent advances of the chemistry of 1 and its derivatives, particularly of
      new chemical reactions having synthetic utility in organic synthesis developed
      mainly in our laboratory. The review is divided into two sections. The first
      section described great utility of divalent positively-charged nitrogen species
      generated from 1 in synthesis. Electrophilic intramolecular cyclization with an
      acylnitrenium ion generated from an N-methoxy- or an N-allyloxy-N-chloroamide
      with anhydrous zinc acetate in nitromethane gave an N-methoxy- or an N-allyloxy
      nitrogen heterocyclic compound, deprotection of which led to formation of the
      corresponding N-hydroxy compound. Treatment of an N-hydroxy- or an N-methoxy-N
      arylamide and the corresponding lactam with various reagents results in removal
      of the hydroxy or methoxy function and introduction of nucleophiles at the ortho
      or para position of the aromatic ring. These methodologies were successfully
      applied by us for the synthesis of the alkaloid, eupolauramine and for new
      oxindoles related to the alkaloid, gelsemine, by others. The second section
      described great utility of N-alkoxyimidoyl halides (2) synthesized from 1.
      Compounds 2 were readily transformed to other functions such as aldehydes,
      cyanides, and oximes. This methodology was successfully applied to the synthesis
      of omega-N-hydroxy-alpha-amino acids in optically pure form which were the key
      intermediates for the synthesis of hydroxamate-containing siderophores.

PMID- 8568637
TI  - [Structures of riboflavin tetraacetate and tetrabutyrate. II. Stacking
      interaction].
AB  - A significant difference in the bond distances or angles and short contacts
      between the two adjacent isoalloxazine (IA) rings in the riboflavin
      tetracarboxylate crystal are attributable to the nonbonded interaction. The
      perturbation of the electronic state in the IA ring accompanied by the
      elimination of the protic solvent well explains an occurrence of charge transfer
      (CT) interaction. This inference is supported by the fact that the IA rings are
      overlapping face to tail in the concentrated solution and the solvation takes
      place at the IA ring. In the frontier molecular orbital theory, it is possible to
      consider that the interaction occurs between the HOMO of the solvent-eliminated
      IA, which acts as a donor, and the LUMO of the solvated IA, which behaves as an
      accepter. The effect of the CT interaction on the stacking interaction can be
      measured quantitatively as the red shift or quenching in the reflection and the
      emission spectra and the signal in the ESR. It is certain that this report gives
      an important clue about the interrelation between the CT interaction and the
      hydrophobic environment in the stacking interaction.

PMID- 8568636
TI  - [Stereoselective synthesis and pharmacological properties of metabolites of new
      antiinflammatory agent. 4'-Acetyl-2'-(2,4-difluorophenoxy)methanesulfonanilide
      (FK3311)].
AB  - Asymmetric reduction of acetophenone (FK3311: 1) and ethyl phenylglyoxylate (7)
      with various chiral reducing agents was investigated in an attempt to synthesize
      both optical isomers of the two metabolites (2 and 5) of 1. The treatment of 1
      with 3,3-diphenyl-1-methyltetrahydro-1H,3H-pyrrolo[1,2-c]-[1,3,2]-
      oxazaborolidine-borane complex (reductants B, C) gave chiral alcohol 2 in a high
      optical purity. On the other hand, reduction of 7 by B
      chlorodiisopinocamphenylborane (reductants E, F) gave the best result among the
      tested reagents. Each isomer of 2 and 5 was examined for in vitro activity to
      inhibit zymosan-induced prostaglandine E2 production, adjuvant-induced arthritis
      for antiinflammatory activity, and acetic acid-induced writhing for analgesic
      activity in comparison with the racemic mixture.

PMID- 8568638
TI  - Studies of rifamycin production by Amycolatopsis mediterranei cells immobilized
      on glass wool.
AB  - Cells of Amycolatopsis mediterranei CBS 42575 were immobilized on glass wool for
      the production of rifamycins B and SV. Glass wool (CORNING type) of 8 microns in
      diameter has a better entrapment capacity for microbial cells of microorganism
      than the other types of glass wool used. The most suitable amount of glass wool
      was 0.8 g/50 ml. The best initial cell concentration used as inoculum was 40 mg
      cells/50 ml. Repeated batch production of rifamycins by immobilized cells on
      glass wool was carried out for 6 repeated batches. The results showed that
      reduction of batch time from 96 h to 48 h does not decrease rifamycin production
      by immobilized cells.

PMID- 8568639
TI  - Bioconversion of methyl ricinoleate to 4-hydroxy-decanoic acid and to gamma
      decalactone by yeasts of the genus Candida.
AB  - The capacity of several strains of yeasts to do the bioconversion of methyl
      ricinoleate into gamma-decalactone, was studied in a medium containing this
      methylic ester of fatty acid as sole carbon source. Amongst the strains which are
      able to do this bioconversion, two types of behaviour are observed: some of the
      strains produce gamma-decalactone during all the incubation in bioconversion
      medium while others produce this aroma compound very quickly and then consume it
      fast too. The tested strains produce at the same time gamma-decalactone and the
      corresponding acid form (4-hydroxy-decanoic acid), and this, in variable
      proportions.

PMID- 8568640
TI  - Biological treatment of distillery waste for pollution-remediation.
AB  - The biological treatment of spent wash from molasses distilleries was
      investigated. Analysis of raw spent wash showed it to be a recalcitrant waste,
      with a high COD of 85,170 mg/l and containing inhibitory phenolic compounds.
      Reverse phase thin layer chromatography identified gallic and vanillic acid
      present in spent wash. The fungi Geotrichum candidum, Coriolus versicolor,
      Phanerochaete chrysosporium and Mycelia sterilia were screened for their ability
      to decolourize spent wash and to reduce the COD level. A 10 day pretreatment with
      Geotrichum candidum at 30 degrees C resulted in reducing the COD by 53.17% and
      total phenols by 47.82%, enabling other bioremediating organisms to grow.
      Coriolus versicolor immobilized in a packed-bed reactor reduced the COD of spent
      wash by a further 50.3%, giving an overall reduction in COD of 77% to 15,780
      mg/l. A small amount of decolourization was achieved (4.2%), although the spent
      wash was still coloured. Present studies are encouraging and indicate that it is
      possible to bioremediate spent wash using a multi-stage treatment process
      involving an initial pretreatment step with Geotrichum candidum.

PMID- 8568641
TI  - Cometabolic degradation of o-cresol and 2,6-dimethylphenol by Penicillium
      frequentans Bi 7/2.
AB  - o-Cresol induced glucose-grown resting mycelia of Penicillium frequentans Bi 7/2
      (ATCC-number: 96048) immediately oxidized o-cresol and other phenols. After
      precultivation on glucose and phenol degradation started after a lag-phase of 24
      hours. Metabolites of o-cresol metabolism were methylhydroquinone, methyl-p
      benzoquinone, 2-methyl-5-hydroxyhydroquinone and 2-methyl-5-hydroxy-p
      benzoquinone. The initial reaction is probably catalyzed by a NADPH dependent
      hydroxylase which is specific for o-cresol. The metabolism of 2,6-dimethylphenol
      (2,6-xylenol) occurred via 2,6-dimethylhydroquinone, 2,6-dimethyl-p-benzoquinone,
      2,6-dimethyl-3-hydroxyhydroquinone, 2,6-dimethyl-3-hydroxy-p-benzoquinone and 3
      methyl-2-hydroxybenzoic acid.

PMID- 8568642
TI  - Salt- and pH-dependent hemagglutination with Kasba virus, a member of the Palyam
      serogroup of the genus Orbivirus.
AB  - Kasba virus grown in BHK21-WI2 cells was tested for hemagglutination (HA) with
      erythrocytes of a variety of species at 4 degrees C, 25 degrees C and 37 degrees
      C. HA was observed at all temperatures with cattle, sheep and goat but not with
      swine, chicken, and goose erythrocytes. The HA was dependent on not only the NaCl
      concentration but also the pH of the diluent. The HA titer significantly improved
      by increasing the NaCl molarity to 0.6 M and standardizing pH to 7.5. The HA
      titer was 16- or 32-fold higher in 0.4 M or 0.6 M solution than in 0.2 M solution
      of not only NaCl but also several other salts. The HA reaction was inhibited by
      specific antibody.

PMID- 8568643
TI  - Studies on bacteriocinogenic Lactobacillus isolates from selected Nigerian
      fermented foods.
AB  - Ten bacteriocin-producing (bacteriocinogenic) Lactobacillus isolates obtained
      from three Nigerian fermented foods namely: kenkey, ogi and wara were tested
      against the following indicator organisms: Lactobacillus plantarum and food borne
      pathogens comprising enterotoxigenic Escherichia coli, enterohaemorrhagic
      Escherichia coli, Serratia, Pseudomonas, Vibrio cholerae, Aeromonas sobria,
      Aeromonas cavice, Salmonella typhimurium, Plesiomonas shigelloides and
      Staphylococcus aureus. All the bacteriocinogenic Lactobacillus were found to
      inhibit L. plantarum while some inhibited some of the food borne pathogens listed
      above. The antimicrobial activities of bacteriocins from L. plantarum KKY12 and
      L. casei OGM12 were caused by proteins detectable in the culture liquids. They
      are designated Plantacin N and Caseicin A and they have narrow antimicrobial
      spectra. Plantacin N from L. plantarum KKY12 was active against L. plantarum,
      Pseudomonas, Aeromonas sobria and Aeromonas cavice whereas Caseicin A from L.
      casei OGM12 inhibited L. plantarum, enterotoxigenic Escherichia coli and Vibrio
      cholerae. Caseicin A is stable at 121 degrees C/15 mins, and both are inactivated
      by proteolytic enzymes. The bacteriocinogenic properties of the local isolates of
      Lactobacillus can help to reduce hygienic risk and the spoilage of fermented
      foods.

PMID- 8568644
TI  - Phenol degradation by Acinetobacter calcoaceticus NCIB 8250.
AB  - Acinetobacter calcoaceticus NCIB 8250 utilizes phenol as sole source of carbon
      and energy via an ortho-cleavage pathway. The presence of ethanol in mixed
      substrate cultivations repressed the utilization of phenol. In fed batch
      cultivation the phenol tolerance was increased at least 2-fold. Maximum
      degradation rates of 150 mg phenol/(1 h) and 280 mg phenol/(g h), respectively
      were observed. Phenol hydroxylase is induced by its substrate and in parallel the
      catechol-1,2-dioxygenase is detectable. The presence of active phenol hydroxylase
      is strongly connected with the phenol degradation. Using a spectrophotometric
      enzyme assay the partially purified phenol hydroxylase was characterized with
      respect to kinetic parameters. The apparent Km values for phenol, FAD and NADPH
      were estimated to be 147 microM, 35 microM and 416 microM, respectively. Both FAD
      and NADPH were essential for maximum activity of the cytoplasmically localized
      enzyme. No substrate inhibition of phenol hydroxylase by phenol was observed up
      to 0.8 mM. The pH and temperature optima were pH 7.8 and 33 degrees C,
      respectively. The partially purified enzyme showed a broad substrate specificity.
      It hydroxylated the three isomeric cresols, chlorophenols and methylated
      chlorophenols. Pyrogallol, 3,4-dihydroxy-L-phenylalanine and resorcinol were
      oxygenated with higher rates than phenol. With the exception of phenol all other
      enzyme substrates tested did not serve as growth substrates.

PMID- 8568646
TI  - GABA-induced facilitation of the periodic bursting activity of oxytocin neurones
      in suckled rats.
AB  - 1. GABAergic innervation of oxytocin neurones is particularly abundant during
      lactation, but little is known about its functional role. In this study, the role
      of GABAA receptors in the suckling-induced bursting activity of oxytocin neurones
      was investigated in lactating rats. GABAA agonists or antagonists were applied by
      pressure injection into the immediate neighbourhood of recorded neurones while
      simultaneous recordings were made from oxytocin neurones in the contralateral
      supraoptic nucleus. 2. GABA and the GABA agonist isoguvacine decreased the basal
      electrical activity while application of GABAA antagonists (picrotoxin and
      gabazine) increased the basal electrical activity. However, in marked and
      unexpected contrast, application of GABA and isoguvacine facilitated or triggered
      milk-ejection reflex bursting activity whereas GABAA antagonists interrupted this
      reflex activity. 3. Systemic injection of hypertonic saline is known to increase
      the firing rate of neurones in the supraoptic nucleus and temporarily to
      interrupt suckling-induced bursting activity. Application of GABA into one
      supraoptic nucleus counteracted this inhibitory effect on milk ejection. 4. These
      observations can be explained if the role of the important GABAergic innervation
      of oxytocin neurones during lactation is to favour the expression of the
      stereotyped suckling-induced bursting activity. It might do this by attenuating
      inputs unrelated to suckling which are incompatible with bursts.

PMID- 8568645
TI  - Mechanisms of intracellular Mg2+ regulation affected by amiloride and ouabain in
      the guinea-pig taenia caeci.
AB  - 1. The effects of amiloride and ouabain on the regulation of the intracellular,
      free Mg2+ concentration ([Mg2+]i) were investigated in the taenia isolated from
      the guinea-pig caecum, using nuclear magnetic resonance (NMR) techniques. 2.
      [Mg2+]i were mainly estimated from the separation of the alpha- and beta-ATP
      peaks observed in 31P NMR spectra. In normal (physiological) and nominally Ca(2+)
      free solutions, [Mg2+]i was approximately 0.3-0.4 mM. Application of either
      amiloride or ouabain in Ca(2+)-free solutions significantly increased [Mg2+]i,
      with only a small change in ATP content. Washout of the drugs reversed the
      changes in [Mg2+]i. 3. Changes in pHi were estimated from: (1) the chemical shift
      of phosphoethanolamine, and (2) solving two relational equations of pHi and
      [Mg2+]i obtained from the beta- and gamma-ATP peaks. Both estimations revealed
      some intracellular alkalosis during application of these two drugs. After
      correction for pHi, a significant increase in [Mg2+]i was still obtained 150 min
      after application of either drug. 4. In the presence of amiloride, simultaneous
      removal of extracellular Mg2+ and Ca2+ significantly depleted intracellular Mg2+.
      This result suggests the presence of an amiloride-insensitive (or less sensitive)
      pathway which passively transports Mg2+ across the plasma membrane. 5. The
      intracellular Rb+ concentration was monitored as an index of Na(+)-K+ pump
      activity, using 87Rb NMR. In Ca(2+)-free solutions containing 5 mM Rb+, the
      intracellular Rb+ concentration was hardly changed by amiloride, but was depleted
      by additional applications of ouabain. Wash-out of ouabain restored the
      intracellular Rb+ in the presence of amiloride. 6. These results are consistent
      with the presence of Na(+)-Mg2+ exchange as an effective Mg(2+)-extruding
      mechanism in smooth muscle. Although many other factors may cause changes in
      [Mg2+]i, it seems likely that amiloride directly inhibits the Na(+)-Mg2+
      exchanger, whilst ouabain does so indirectly through reduction of the Na+
      gradient across the plasma membrane.

PMID- 8568647
TI  - Role of nitric oxide in tachykinin-induced increase in potential difference of
      rabbit tracheal mucosa.
AB  - 1. The effect of tachykinins on transepithelial potential difference (PD) of
      rabbit trachea and possible involvement of nitric oxide (NO) generation in vivo
      were investigated. 2. Perfusion of tracheal mucosa with neurokinin A (NKA) or
      substance P (SP) dose dependently increased PD in the presence of amiloride, with
      the potency being NKA > SP, but neurokinin B (NKB) had no effect. 3. Application
      of NG-nitro-L-arginine methylester (L-NAME, 10(-3) M) attenuated the NKA-induced
      increase in the amiloride-sensitive PD, causing a rightward displacement of the
      dose-response curve by approximately 1.0 log U, whereas NG-nitro-D-arginine
      methylester (D-NAME, 10(-3) M) did not. 4. The inhibitory effect of L-NAME was
      reversed by L-arginine (10(-2) M) but not by D-arginine (10(-2) M). 5. The
      release of NO was determined by a real-time measurement of NO concentration
      ([NO]) in the perfusate using specific amperometric sensors for this molecule. 6.
      NKA and SP increased [NO] in a dose-dependent manner, the maximal increase from
      the baseline value being 114 +/- 11 nM (mean +/- S.E.M., P < 0.001) and 54 +/- 6
      nM (P < 0.01), respectively. 7. Histochemistry for NADPH diaphorase activity
      showed a strong staining within the epithelial cells. 8. We conclude firstly that
      tachykinins increase amiloride-sensitive PD in vivo, which probably reflects Cl-
      movement from the submucosa toward the respiratory lumen in tracheal mucosa, and
      secondly that NO generation by epithelial cells may be involved in this process.

PMID- 8568648
TI  - Adenosine-induced apoptosis in chick embryonic sympathetic neurons: a new
      physiological role for adenosine.
AB  - 1. A newly found action of adenosine in neurons, which may have an important
      physiological function in the growth and development of the sympathetic nervous
      system, is described. Adenosine (1-100 microM) inhibited neurite outgrowth within
      the first 24 h and killed about 80% of sympathetic neurons supported by nerve
      growth factor over the next 2 days in culture. Neurons supported by excess KCl,
      forskolin or phorbol 12,13-dibutyrate were equally susceptible to the toxic
      actions of adenosine. Inosine, guanosine or hypoxanthine (all 100-300 microM)
      were without effect on neuronal growth and survival. 2. Specific agonists of
      adenosine A1 and A2 receptors were not neurotoxic, and toxic effects of adenosine
      were not antagonized by aminophylline. These results rule out involvement of
      adenosine receptors and the adenylyl cyclase-cAMP signalling system in neurotoxic
      actions of adenosine. 3. Adenosine toxicity was prevented by inhibitors of the
      adenosine membrane transporter, suggesting an intracellular site of action of
      adenosine. 4. Inhibitors of adenosine deaminase dramatically facilitated the
      toxic action so that physiologically relevant concentrations of adenosine were
      neurotoxic. 5. Adenosine kinase activity of sympathetic neurons was dose
      dependently inhibited by 5'-iodotubercidin (3-100 nM). 5'-Iodotubercidin (100 nM)
      completely protected neurons against toxicity of adenosine plus adenosine
      deaminase inhibitors. These results provide convincing evidence that
      phosphorylation of the nucleoside is an essential requirement for initiation of
      adenosine toxicity. 6. Sympathetic neurons were successfully rescued from the
      lethal effects of adenosine deaminase inhibitor plus adenosine by uridine or 2
      deoxycytidine, but not by nicotinamide or 2-deoxyguanosine, suggesting that
      depletion of pyrimidine nucleotides by phosphorylated adenosine compounds and
      consequent inhibition of DNA synthesis produces neuronal death. 7. DNA
      fragmentation, assessed by the fluorescent dye bisbenzimide and by the TUNEL
      (terminal deoxynucleotidyl transferase-mediated nick end labelling) method,
      indicated that neuronal death induced by adenosine was apoptotic. 8. We conclude
      that adenosine deaminase and adenosine kinase play an important role in the
      metabolism of intracellular concentrations of adenosine and thereby regulate the
      growth and development of sympathetic neurons. Our study highlights, for the
      first time, the importance of adenosine as a mediator of programmed cell death of
      neurons supported by nerve growth factor.

PMID- 8568649
TI  - Two distinct modes of Ca2+ signalling by ACh in rat pancreatic beta-cells:
      concentration, glucose dependence and Ca2+ origin.
AB  - 1. Calcium signalling by acetylcholine (ACh) in single rat pancreatic beta-cells
      was studied. The cytosolic free Ca2+ concentration ([Ca2+]i) was measured by dual
      wavelength fura-2 microfluorometry. 2. In the presence of basal glucose (2.8 mM),
      10(-6) to 10(-4) M ACh (high ACh) transiently increased [Ca2+]i. The [Ca2+]i
      response to 10(-5) M ACh was little altered under Ca(2+)-free conditions. Brief
      pulses of 10(-5) M ACh evoked successive [Ca2+]i responses, which were
      progressively inhibited by 0.2-0.5 microM thapsigargin, a specific inhibitor of
      the endoplasmic reticulum (ER) Ca2+ pump. 3. Elevation of glucose to 8.3 mM, a
      concentration which stimulates insulin release, increased [Ca2+]i to an initial
      peak followed by a sustained, moderate elevation. Addition of 10(-8) to 10(-7) M
      ACh (low ACh) evoked a further increase in [Ca2+]i. The [Ca2+]i response to 10(
      7) M ACh was completely inhibited under Ca(2+)-free conditions by 1 microM
      nitrendipine, a blocker of L-type Ca2+ channels, and by 100 microM diazoxide, an
      opener of ATP-sensitive K+ channels. 4. In the presence of 8.3 mM glucose,
      [Ca2+]i responses to 10(-5) M ACh were reduced but not abolished by Ca(2+)-free
      conditions, nitrendipine and diazoxide. Successive [Ca2+]i transients induced by
      10(-5) M ACh pulses in the presence of nitrendipine were progressively inhibited
      by thapsigargin. 5. The results revealed two distinct modes of Ca2+ signalling:
      low ACh increases [Ca2+]i by stimulating Ca2+ influx through voltage-dependent L
      type Ca2+ channels only in the beta-cells in which glucose has already elevated
      [Ca2+]i, while high ACh increases [Ca2+]i at basal as well as stimulatory glucose
      concentrations by releasing Ca2+ from the ER. The former mechanism is likely to
      relate to the potentiator action and the latter to the initiator action of ACh on
      insulin release. High ACh and elevated glucose provoke both modes of Ca2+
      signalling.

PMID- 8568650
TI  - Effects of hypothalamic thermal stimuli on sympathetic neurones innervating skin
      and skeletal muscle of the cat hindlimb.
AB  - 1. Postganglionic neurones supplying hairless and hairy skin of the cat hindlimb
      were analysed for their responses to thermal stimuli applied to the anterior
      hypothalamus and spinal cord in anaesthetized and artificially ventilated cats.
      Activity was recorded from multi- and single-unit bundles which were isolated
      from peripheral nerves. The neurones were functionally identified as cutaneous
      vasoconstrictor (CVC) and muscle vasoconstrictor (MVC) neurones. Activity in
      sudomotor (SM) neurones was either monitored indirectly by recording the phasic
      negative deflections of the skin potential from the surface of the hairless skin,
      or in some experiments additionally by recording activity directly from the SM
      axons. 2. The activity in forty-one out of forty-four multi-unit and six out of
      six single-unit CVC bundles was inhibited, in a graded manner, by hypothalamic
      warming. An increase in the temperature of the surface of hairless skin followed
      the decrease in activity of the CVC neurones supplying it. Large changes in skin
      temperature only followed decreases in CVC activity of more than 40%. Cooling of
      the hypothalamus had only weak transient effects on CVC neurones. 3. Simultaneous
      warming of hypothalamus and spinal cord had multiplicative effects on the
      activity in CVC neurones. Subthreshold warming of one structure increased the
      response to warming of the other one and reduced the threshold temperature. 4. SM
      neurones were not affected by hypothalamic warming, but activated during
      hypothalamic cooling. 5. MVC neurones were weakly activated during hypothalamic
      warming only if arterial blood pressure decreased, otherwise they were
      unaffected. It is likely that this activation was due to secondary unloading of
      arterial baroreceptors. 6. Two silent postganglionic neurones projecting to skin
      were activated during hypothalamic warming. These neurones may have had a
      vasodilatory function. 7. Rhythmicity of the activity in CVC neurones, related to
      the cycle of artificial ventilation, increased during hypothalamic warming
      whereas that of MVC neurones was unchanged. 8. The functionally highly specific
      responses to hypothalamic warming in CVC neurones indicate a pathway from the
      hypothalamus that is specific for CVC neurones, in contrast to MVC and SM
      neurones. This central pathway is integrated with other spinal and supraspinal
      reflex pathways that determine the characteristic reflex pattern of CVC neurones
      to somatic and visceral stimuli and possibly with pathways that generate other
      physiological changes during hypothalamic warming (e.g. increase in respiratory
      drive).

PMID- 8568651
TI  - Estimated potassium reflection coefficient in perfused proximal convoluted
      tubules of the anaesthetized rat in vivo.
AB  - 1. As yet there is no definitive description of the mechanism and route by which
      K+ reabsorption is achieved in the proximal convoluted tubule (PCT). We have
      assessed the contribution of convective K+ transport to net potassium ion flux
      (JK) by estimating the reflection coefficient of K+ (sigma K) in the proximal
      tubule of anaesthetized rats previously prepared for in vivo microperfusion. 2.
      Alterations in the luminal concentration of the impermeant solute raffinose in
      single-perfused (lumen only) and double-perfused (lumen and capillaries) PCTs
      were found to change fluid reabsorption in a predictable fashion. 3. Net
      potassium ion flux (JK) in single- and double-perfused tubules was significantly
      correlated with net fluid flux (Jv), suggesting that convective K+ transport may
      be a significant factor in overall K+ transport by the PCT. 4. Estimates of sigma
      K in single- and double-perfused tubules were very similar (0.14 +/- 0.06 and
      0.13 +/- 0.05, respectively), even though K+ diffusion was not strictly
      controlled in the former group. The maximum effect of 'pseudo-solvent' drag in
      double-perfused tubules was estimated to give a sigma K of 0.40. This low value
      for sigma K suggests that true convection/solvent drag may be an important
      driving force for the reabsorption of K+ from the PCT of the rat.

PMID- 8568652
TI  - Involvement of renal kallikrein in the regulation of bicarbonate excretion in
      rats.
AB  - 1. The experiments reported here were performed to test the hypothesis that renal
      kallikrein is involved in the regulation of acid-base balance. 2. The bicarbonate
      concentration and the kallikrein activity in the spontaneously voided urine of
      conscious rats (experiment 1) were inversely correlated (correlation coefficient
      (r) = -0.63, P < 0.0001). The correlation was even greater when the urinary
      bicarbonate concentration was expressed per milligram excreted creatinine (r = 
      0.74, P < 0.00002). 3. Intravenous injection of the kallikrein inhibitor
      aprotinin in barbiturate-anaesthetized rats (experiment 2) reduced urinary
      kallikrein activity (P < 0.05) and increased bicarbonate excretion rate (P <
      0.012). 4. Renal arterial infusion of aprotinin in barbiturate-anaesthetized rats
      (experiment 3) reduced urinary kallikrein activity (120 min, P < 0.01), and
      increased bicarbonate excretion rate (120 min, P < 0.01). Animals infused with
      the inhibitor developed a moderate metabolic acidosis (base excess: control, 2.9
      +/- 0.7 mM (mean +/- S.E.M.); experimental, -8.1 +/- 0.7 mM; P < 0.05). 5. The
      bicarbonate concentration of urine fractions obtained after retrograde injection
      of kallikrein through the ureter into the collecting duct system of barbiturate
      anaesthetized rats was lower than that from kidneys administered the vehicle
      (experiment 4; P < 0.001). A retrograde injection of bradykinin was without
      effect (experiment 5). 6. We conclude that renal kallikrein is involved in the
      regulation of urinary bicarbonate excretion. Increased intraluminal activity of
      the enzyme reduces, and decreased kallikrein activity increases, bicarbonate
      excretion. The enzyme may be a component of a negative feedback loop controlling
      the hydrogen ion activity of the extracellular space.

PMID- 8568653
TI  - Effect of insulin on Na+,K(+)-ATPase in rat collecting duct.
AB  - 1. The collecting duct is involved in the whole antinatriuretic effect of
      insulin, as indicated in vitro by the stimulatory effect of the hormone on
      ouabain-sensitive 86Rb+ uptake. Since Na+,K(+)-ATPase drives Na+ reabsorption,
      the contribution of the Na+ pump to the effect of insulin was investigated in rat
      isolated cortical and outer medullary collecting duct. 2. Insulin enhanced
      ouabain-sensitive 86Rb+ uptake in the absence, as well as in the presence, of
      either 5 x 10(-4) M amiloride or 10(-3) M hydrochlorothiazide (HCT). Maximal
      ouabain-sensitive 86Rb+ uptake, measured in Na(+)-loaded tubules, was also
      enhanced by insulin. The insulin effect persisted both in the absence of external
      Na+, when the Na+,K(+)-ATPase operates in a Rb(+)-Rb+ exchange mode, and in
      tubules depolarized by a high external concentration (20 mM) of Rb+ or by
      addition of 3 mM Ba2+. 3. Insulin treatment did not alter the intracellular Na
      and K concentrations, the specific binding of [3H]ouabain measured in intact
      tubules, or the hydrolytic activity of Na+,K(+)-ATPase measured after
      permeabilization of the tubule cells. 4. In conclusion, in the rat collecting
      duct, insulin increased Na+,K(+)-ATPase-mediated cation transport independently
      of Na+ availability, membrane potential and recruitment of pump units. The effect
      of insulin was lost after cell permeabilization, suggesting the presence of a
      cytosolic factor which controls the turnover of Na+,K(+)-ATPase.

PMID- 8568654
TI  - Modulation of erythropoietin formation by changes in blood volume in conscious
      dogs.
AB  - 1. A possible influence of the filling of the circulatory system on the plasma
      concentration of erythropoietin, which is the major regulator of erythrocyte
      formation, was investigated in conscious dogs. 2. Over an experimental period of
      5 h, the animals were subjected to either haemorrhage (hypovolaemia), blood
      volume expansion (hypervolaemia), or exchange transfusion of blood with dextran
      (isovolaemic anaemia). 3. A reduction of blood volume by 20% induced by
      haemorrhage increased plasma erythropoietin levels approximately 1.5-fold in the
      absence of significant changes in haematocrit. 4. An expansion of blood volume by
      12% induced by an intravenous infusion of dextran did not change plasma
      erythropoietin levels, although the haematocrit decreased by 0.04. 5. A reduction
      of the haematocrit by 0.12 in the absence of changes in blood volume induced by
      an isovolaemic exchange transfusion (dextran vs. blood) increased plasma
      erythropoietin levels approximately 3-fold. 6. Total renal oxygen supply did not
      change in any of the three experimental protocols. 7. These data indicate that in
      dogs the erythropoietin production rate is modulated by changes in blood volume,
      and suggest a possible role of erythropoietin in the regulation of blood volume.

PMID- 8568655
TI  - Mechanics of pulsatile transpyloric flow in the pig.
AB  - 1. In eight conscious pigs equipped with gastric and duodenal cannulae, the
      relationship of transpyloric flow to gastro-duodenal motor events was evaluated
      during gastric emptying of 1000 ml of saline. Rates of liquid gastric emptying
      were correlated with pressures at the antrum, pylorus and duodenum, recorded by a
      sleeve sensor and multiple perfused side-holes. Transpyloric flow was recorded
      concurrently by continuous collection and weighing of the duodenal effluent. 2.
      In three pigs the above measurements were repeated during concurrent
      videofluoroscopy of gastric emptying after adding 100 ml of liquid barium to the
      gastric instillate. 3. The mean volume of saline emptied in 30 min was 627 +/-
      51.2 ml. Pulsatile flow accounted for 71% of total emptying. Pulses had a mean
      flow rate of 3.9 +/- 0.44 ml s-1. Most flow pulses (59%) occurred during the
      first 5 min of emptying. 4. Distinctive, low-amplitude (4.8 +/- 0.33 mmHg),
      relatively long-lasting (15.8 +/- 0.46 s) antral pressure waves were associated
      with 58% of flow pulses. In all antral pressure recording points, the first and
      longest duration component of these pressure waves had an identical timing,
      amplitude and waveform consistent with pressurization of the entire antrum
      gastric cavity. 5. Videofluoroscopy and concurrent manometry showed that these
      antral common cavity pressure waves were associated with non-lumen-occlusive
      contractions of the gastric wall, initially observed at the corpus which
      propagated down to the pylorus; 93% of these contractions became lumen occlusive
      in the terminal antrum and pylorus when pressure waves of a unique pattern for
      each recording point were recorded at this level. 6. The onset of 68% of the flow
      pulses which accounted for 62% of pulsatile emptying occurred in the interval
      (mean 7.9 +/- 0.65 s) between the onset of the common cavity wave and the onset
      of localized, lumen-occlusive distal antral-pyloric pressure waves. 7. These
      findings indicate that in the pig, pulsatile emptying of non-nutrient liquids
      into the duodenum occurs predominantly during the non-lumen-occlusive stage of a
      propagated gastric contraction, which is recognisable as a common cavity pressure
      wave. This is a previously inadequately recognized pattern of gastric pumping.

PMID- 8568656
TI  - Role of antral intramural neural pathways in control of gastric emptying in the
      pig.
AB  - 1. The role of antral intramural pathways in the control of antropyloric motility
      and gastric emptying was evaluated in five conscious pigs equipped with chronic
      gastric and duodenal cannulae. Neural pathways were divided by transection and re
      anastomosis of the antrum 2 cm proximal to the pylorus. Concurrent measurements
      of gastric emptying, transpyloric flow and antropyloric motility were performed
      before and 6 weeks after surgery. 2. Antral transection retarded gastric
      emptying, only 36% of 1000 ml saline being emptied in 30 min compared with 62%
      before transection. Transection did not alter the number of transpyloric flow
      pulses (22.0 +/- 4.0 cf. 24.4 +/- 3.2 pre-transection), but reduced (P < 0.01)
      the volume of flow pulses substantially (8.6 +/- 0.4 cf. 18.7 +/- 1.5 ml pre
      transection). 3. Antral transection was associated with a reduction in the rate
      of distal antral pressure waves (P < 0.05), but no alteration in the rate of
      phasic low level pressurization of the entire gastric content by gastric
      contractions (gastric common cavity pressure waves). However, transection was
      associated with a significant (P < 0.05) shortening of the interval between the
      onset of gastric common cavity pressure waves, and the onset of lumen-occlusive
      pyloric pressure waves generated by the same contraction sequence (3.2 +/- 0.3
      cf. 7.9 +/- 0.6 s). 4. Transection did not alter the inhibition of antral
      pressure waves, stimulation of localized pyloric pressure waves, and retardation
      of gastric emptying produced by infusion of 25% dextrose into the duodenum. 5.
      These studies suggest that antral intramural nerves regulate the emptying of
      liquids from the stomach by modulating the timing of pyloric closure in relation
      to phasic gastric antral and corpus contractions. 6. Distal antral intramural
      neural pathways do not appear to play a major role in the suppression of antral
      motor activity produced by duodenal glucoreceptors.

PMID- 8568657
TI  - Non-linear relationship between O2 uptake and power output at high intensities of
      exercise in humans.
AB  - 1. A slow component to pulmonary oxygen uptake (VO2) is reported during prolonged
      high power exercise performed at constant power output at, or above,
      approximately 60% of the maximal oxygen uptake. The magnitude of the slow
      component is reported to be associated with the intensity of exercise and to be
      largely accounted for by an increased VO2 across the exercising legs. 2. On the
      assumption that the control mechanism responsible for the increased VO2 is
      intensity dependent we hypothesized that it should also be apparent in multi
      stage incremental exercise tests with the result that the VO2-power output
      relationship would be curvilinear. 3. We further hypothesized that the change in
      the VO2-power output relationship could be related to the hierarchical
      recruitment of different muscle fibre types with a lower mechanical efficiency.
      4. Six subjects each performed five incremental exercise tests, at pedalling
      rates of 40, 60, 80, 100 and 120 rev min-1, over which range we expected to vary
      the proportional contribution of different fibre types to the power output.
      Pulmonary VO2 was determined continuously and arterialized capillary blood was
      sampled and analysed for blood lactate concentration ([lactate]b). 5. Below the
      level at which a sustained increase in [lactate]b was observed pulmonary VO2
      showed a linear relationship with power output; at high power outputs, however,
      there was an additional increase in VO2 above that expected from the
      extrapolation of that linear relationship, leading to a positive curvilinear VO2
      power output relationship. 6. No systematic effect on the magnitude or onset of
      the 'extra' VO2 was found in relation to pedalling rate, which suggests that it
      is not related to the pattern of motor unit recruitment in any simple way.

PMID- 8568658
TI  - Lactate and H+ uptake in inactive muscles during intense exercise in man.
AB  - 1. The present study examined how uptake of lactate and H+ in resting muscle is
      affected by blood flow, arterial lactate concentration and muscle metabolism. 2.
      Six males subjects performed intermittent arm exercise in two separate 32 min
      periods (Part I and Part II) and in one subsequent 20 min period in which one leg
      knee-extensor exercise was also performed (Part III). The exercise was performed
      at various intensities in order to obtain different steady-state arterial blood
      lactate concentrations. In the inactive leg, femoral venous blood flow (draining
      about 7.7 kg of muscles) was measured and femoral arterial and venous blood was
      collected frequently. Biopsies were taken from m. vastus lateralis of the
      inactive leg at rest and 10 and 30 min into both Part I and Part II as well as 10
      min into recovery from Part II. 3. The arterial plasma lactate concentrations
      were 7, 9 and 16 mmol l-1 after 10 min of Parts I, II and III, respectively, and
      the corresponding arterial-venous difference (a-vdiff) for lactate in the resting
      leg was 1.3, 1.4 and 2.0 mmol l-1. The muscle lactate concentration was 2.8 mmol
      (kg wet wt)-1 after 10 min of Part I and remained constant throughout the
      experiment. During Parts I and II, a-vdiff lactate decreased although the
      arterial lactate concentration and plasma-muscle lactate gradient were unaltered
      throughout each period. Thus, membrane transport of lactate decreased during each
      period. 4. Blood flow in the inactive leg was about 2-fold higher during arm
      exercise compared to the rest periods, resulting in a 2-fold higher lactate
      uptake. Thus, lactate uptake by inactive muscles was closely related to blood
      flow. 5. Throughout the experiment a-vdiff for actual base excess and for lactate
      were of similar magnitude. Thus, in inactive muscles lactate uptake appears to be
      coupled to the transport of H+.

PMID- 8568659
TI  - Detection of movements imposed on human hip, knee, ankle and toe joints.
AB  - 1. The angular displacements necessary for 70% correct detection were determined
      in normal subjects at the hip, knee and ankle joints, and the interphalangeal
      joint of the big toe. Angular velocities between 0.1 and 50 deg s-1 were tested.
      The hip and knee joints were tested in slight flexion and the ankle and toe
      joints were tested in the mid-range of the normal excursion. The joints were
      carefully supported for testing and the muscles acting at the joints were
      relaxed. 2. When detection thresholds and velocities were assessed in terms of
      angular displacements and angular velocities, proprioceptive performances at the
      hip, knee and ankle joints were superior to that at the toe joint. 3. When
      detection levels and displacement velocities were expressed in terms of linear
      displacements and velocities at the tip of the extended toe for all four joints,
      instead of in angular terms, the ankle gave the best performance and the hip and
      knee the worst. 4. The detection level and velocity data were expressed also in
      terms of proportional changes in the fascicle lengths of muscles operating these
      joints. Analysis in these terms showed that performance was similar at the hip,
      knee and ankle joints, but that performance for the toe was much poorer than for
      the other joints. 5. These results for the hip, knee and ankle are similar to
      those previously measured for the elbow and distal interphlangeal joint of the
      finger, and are consistent with the theory that muscle fascicle length is the
      variable of significance to the central nervous system. However, the
      proprioceptive performance at the big toe is notably poorer than all other joints
      studied and analysed in terms of this variable.

PMID- 8568660
TI  - Perception of movement at the human ankle: effects of leg position.
AB  - 1. Recent studies show that subjects perceive smaller ankle movements when they
      are upright in the standing position than when they are seated. To examine this
      improvement, the ability to perceive ankle movements was tested in five positions
      of body, knee and ankle. Subjects reported the direction of slow ramp movements
      of the ankles. 2. The threshold for perceiving ankle movements was unchanged when
      only one ankle was moved rather than both together. When seated with the knees
      bent and ankles slightly plantarflexed, subjects perceived movements of 0.65 deg
      at 0.05 deg s-1. However, when upright or when seated with their knees and ankles
      in the standing position, subjects perceived movements that were one-third of
      this size. 3. These findings show that the knee and ankle positions, rather than
      being upright, explain the better performance in the standing position. During
      standing, knee extension and ankle dorsiflexion stretch the calf muscles. Thus,
      enhanced input from intramuscular stretch receptors appears responsible for the
      better performance.

PMID- 8568661
TI  - Mechanism for reflex reversal during walking in human tibialis anterior muscle
      revealed by single motor unit recording.
AB  - 1. A reversal in the sign of a cutaneous reflex during walking was recently
      described in the human. Such reversals were most clearly seen in muscles that
      were active in two parts of the step cycle, such as the tibialis anterior (TA).
      The current study determined whether the reversal resulted from differential
      activation of a single group of motor units. 2. Single motor units were recorded
      from the TA muscle of healthy human subjects while they walked on a treadmill
      with a splint that limited motion of the ankle joint. The majority of motor units
      from which recordings were made (43 out of 46) were active in both the swing
      phase and the transition from swing to stance, indicating that the two bursts of
      activity from the TA muscle do not represent the activity of two separate
      populations of motor units. 3. The firing behavior of three motor units was
      observed during walking steps when stimuli were applied to the posterior tibial
      nerve during either the swing phase or the transition from swing to stance. The
      post-stimulus time histograms indicated that the same motor unit was excited
      during the swing phase, and inhibited during the transition from swing to stance.
      4. The results support the hypothesis that there are parallel excitatory and
      inhibitory pathways from cutaneous afferents to single motoneurones of the TA
      muscle. A shift in balance between the two pathways as a function of the step
      cycle most probably generates the reflex reversal observed.

PMID- 8568662
TI  - Intracellular calcium and force in single mouse muscle fibres following repeated
      contractions with stretch.
AB  - 1. The role of the myoplasmic free Ca2+ concentration ([Ca2+]i) in the reduction
      of muscle force following contractions with stretch was investigated in single
      fibres from mouse toe muscle. Muscle fibres were either stretched by 25% of their
      optimum length (Lo) for ten tetani (Protocol I) or stretched by 50% of Lo for
      between ten and thirty tetani (Protocol II). Indo-1 was used to measure [Ca2+]i.
      2. In each protocol the stretch series was compared with isometric controls; the
      stretch series always resulted in greater changes in muscle properties than in
      the isometric controls. The observed changes were (i) reduced tetanic force, (ii)
      reduced tetanic [Ca2+]i, (iii) increased resting [Ca2+]i and (iv) the greater
      relative reduction in force at low stimulus frequencies (30 and 50 Hz) compared
      with high (100 Hz). These changes were maintained for up to 60 min. 3. Stretching
      a resting muscle fibre had no effect on the subsequent [Ca2+]i or force. 4.
      Following Protocol I 10 mM caffeine restored tetanic force to pre-stretch levels.
      Tetanic [Ca2+]i vs. force curves were constructed pre- and post-stretch and
      showed that neither the maximum Ca(2+)-activated force nor the Ca2+ sensitivity
      of the muscle fibres post-stretch was significantly different from control. The
      force reduction, therefore, appears to be the result of reduced tetanic [Ca2+]i.
      5. The more severe stretching regimen of Protocol II resulted in a much greater
      reduction in force than Protocol I. Ten millimolar caffeine did not restore
      control force. Comparison of the [Ca2+]i-force relationships pre- and post
      stretch showed that the reduction in tetanic force was caused by a combination of
      a reduced tetanic [Ca2+]i, reduced maximum Ca(2+)-activated force and reduced
      Ca2+ sensitivity. 6. Following both protocols the resting [Ca2+]i showed a small
      rise which persisted for at least 60 min. This elevated [Ca2+]i was associated
      with a reduction in the pump rate of the sarcoplasmic reticulum Ca2+ pump. 7.
      This study establishes that reduced Ca2+ release and reduced Ca2+ sensitivity
      contribute to the reduction in force generating capacity of single mammalian
      muscle fibres following active stretches.

PMID- 8568663
TI  - Role of nitric oxide in exercise hyperaemia during prolonged rhythmic
      handgripping in humans.
AB  - 1. We sought to determine whether the vasodilating molecule nitric oxide (NO)
      contributes to the forearm hyperaemia observed during prolonged rhythmic
      handgripping in humans. 2. Two bouts of exercise were performed during
      experimental protocols conducted on separate days. During each protocol the
      subject performed a 10 min and a 20 min bout of rhythmic (30 min-1) handgripping
      at 15% of maximum. Two exercise bouts were required to facilitate pharmacological
      interventions during the second protocol. Blood flow in the exercising forearm
      was measured every minute with plethysmography during brief pauses in the
      contractions. During both exercise bouts in the first protocol, forearm blood
      flow increased 2- to 3-fold above rest after 1 min of handgripping and remained
      constant at that level throughout the exercise. 3. During the 10 min bout of
      exercise in the second protocol, acetylcholine was given via a brachial artery
      catheter at 16 micrograms min-1 for 3 min to evoke NO release from the vascular
      endothelium. This caused forearm blood flow to increase above the values observed
      during exercise alone. 4. During the 20 min trial of handgripping in the second
      protocol, the NO synthase blocker NG-monomethyl-L-arginine (L-NMMA) was infused
      in the exercising forearm via the brachial catheter after 5 min of handgripping.
      The L-NMMA was infused at 4 mg min-1 for 10 min. 5. L-NMMA during exercise caused
      forearm blood flow to fall to values approximately 20-30% lower than those
      observed during exercise alone. When ACh was given during exercise after L-NMMA
      administration the rise in blood flow was also blunted, indicating blockade of NO
      synthase. These data suggest NO plays a role in exercise hyperaemia in humans.

PMID- 8568665
TI  - A mini Cl- channel sensitive to external pH in the basolateral membrane of guinea
      pig parietal cells.
AB  - 1. Voltage-independent whole-cell Cl- currents were recorded from both single,
      isolated parietal cells and parietal cells within gastric glands obtained from
      the fundus of guinea-pig stomach. 2. The Cl- currents were rapidly suppressed by
      a Cl- channel blocker, NPPB (5-nitro-2-(3-phenylpropylamino)-benzoate), added to
      the (basolateral) bathing solution in a concentration-dependent manner with a
      half-maximal inhibition concentration of 12 microM. 3. The selectivity sequence
      among anions was I- > Br- > Cl- > F-, corresponding to Eisenman's sequence I. 4.
      The Cl- currents were independent of cytosolic Ca2+, cyclic AMP, cyclic GMP, GTP
      gamma-S and cell volume, and were not affected by application of acid
      secretagogues, omeprazol, arachidonic acid or prostaglandin E2. 5. Reduction of
      pH in the (basolateral) bathing solution immediately inhibited the Cl- current
      with a pK (-log of KD) of 6.3, whereas changes in intracellular pH had no effect.
      6. The single-channel conductance was estimated to be 0.46-0.6 pS by variance
      noise analysis during inhibition of whole-cell Cl- currents by NPPB or acidic pH.
      7. It is concluded that pH-sensitive 'mini' Cl- channels, with a sub-picosiemens
      unitary conductance, exist in the basolateral membrane of guinea-pig parietal
      cells.

PMID- 8568664
TI  - A non-selective cation current activated via the multifunctional Ca(2+)
      calmodulin-dependent protein kinase in human epithelial cells.
AB  - 1. Activation of macroscopic membrane currents by intracellular calcium ([Ca2+]i)
      signalling pathways was examined in human T84 epithelial cells, a model secretory
      cell line. 2. Elevation of [Ca2+]i by either the calcium ionophore A23187 (1
      microM) or the cholinergic agonist carbachol, led to the transient activation of
      both a chloride and cation current in single voltage clamped cells. The channels
      underlying the cation conductance were found to be equally permeable to external
      Na+, K+ and Cs+, but impermeable to the large organic cations tetraethylammonium
      and N-methyl-D-glucamine (NMDG). These observations indicate that the cation
      channels are non-selective with respect to monovalent cations. 3. Persistent
      activation of both the chloride and non-selective cation currents by [Ca2+]i was
      observed following inhibition of cellular phosphatase activity by the phosphatase
      inhibitor microcystin LR or the ATP analogue ATP gamma S. This finding strongly
      suggests the presence of a phosphorylation event in the calcium-dependent
      activation pathway for both currents. 4. Intracellular dialysis with peptide
      inhibitors of the multifunctional Ca(2+)-calmodulin-dependent protein kinase (CaM
      kinase) blocked the activation of both the chloride and cation conductances by
      elevated [Ca2+]i. Dialysis with an inactive control peptide had no effect on the
      activation of either current. CaM kinase thus appears to be critically involved
      in the calcium-dependent activation of both the chloride and cation currents in
      these cells. 5. Associated with the whole-cell cation conductance were
      macroscopic tail currents observed at the chloride reversal potential. The
      distinct kinetic properties of these tail currents were used as a biophysical
      'signature' of the whole-cell conductance. 6. In excised, inside-out membrane
      patches, [Ca2+]i activated single cation channel activity. These channels had a
      mean conductance of 20 pS, were impermeable to NMDG, and their mean open
      probability increased at positive membrane potentials. The properties of these
      single channel events thus closely resemble those reported previously for calcium
      activated cation channels in epithelia. 7. Using a novel 'tail current' voltage
      clamp protocol in excised membrane patches, we observed that ensemble averages of
      single cation channel events reproduced the behaviour and kinetic properties of
      the macroscopic tail currents of the calcium-activated cation conductance. This
      finding provides evidence that the observed single channel events probably
      underlie the macroscopic cation current recorded from intact cells. 8. The
      results from this study demonstrate that CaM kinase mediates the calcium
      dependent activation of both a chloride and a non-selective cation current in
      human T84 epithelial cells. Using single channel recordings, we believe we have
      identified the corresponding whole-cell current for the 20-40 pS calcium
      activated cation channel activity reported previously in epithelia and other cell
      preparations. Physiologically, a calcium-activated inward cation current would
      allow sodium influx in association with calcium-dependent electrolyte and protein
      secretion. Thus CaM kinase-dependent activation of cation channels may serve as a
      co-ordinated influx pathway to balance the efflux and influx of osmotically
      active solutes as part of an overall cell volume regulatory mechanism.

PMID- 8568666
TI  - A maxi Cl- channel coupled to endothelin B receptors in the basolateral membrane
      of guinea-pig parietal cells.
AB  - 1. To study endothelin (ET) receptors in guinea-pig stomach, ET-binding assays
      and in vitro autoradiography were performed on fundic cell suspensions and on
      sections of the fundus, respectively. ETA and ETB receptor subtypes were found to
      coexist in the parietal cells. 2. Endothelin 1 (ET-1) added to the (basolateral)
      bathing solution was found to activate noisy whole-cell Cl- currents within about
      1 min in both single, isolated parietal cells and those within gastric glands
      obtained from the fundus. 3. ET-1-induced Cl- currents were rapidly blocked by a
      Cl- channel blocker (NPPB) added to the (basolateral) bathing solution in a
      concentration-dependent manner with a half-maximum inhibition concentration of 33
      microM. 4. The anion selectivity sequence of the ET-1-induced conductance was I-
      > Br- > Cl- > F-, corresponding to Eisenman's sequence I. 5. Changes in
      extracellular pH between 5 and 8 did not affect the ET-1-induced activation of Cl
      currents. 6. Similar activating effects were also observed with ET-3 and a
      specific ETB receptor agonist (IRL1620). An ETB receptor antagonist (IRL1720)
      prevented the ET-1 effect, whereas an ETA-selective antagonist (FR139317 or
      BQ123) failed to antagonize the ET-1 effect. 7. In the whole-cell mode, unitary
      Cl- channel events could be observed in association with ET-1-activated
      macroscopic currents. The single-channel conductances were around 200 and 350 pS
      at negative and positive membrane potentials, respectively. 8. It is concluded
      that gastric parietal cells of guinea-pig possess pH-insensitive 'maxi' Cl-
      channels coupled to ETB receptors in the basolateral membrane.

PMID- 8568667
TI  - Evidence for limbic system activation during CO2-stimulated breathing in man.
AB  - 1. The role of supra-brainstem structures in the ventilatory response to inhaled
      CO2 is unknown. The present study uses positron emission tomography (PET), with
      infusion of H2(15)O, to measure changes in relative regional cerebral blood flow
      (rCBF) in order to identify sites of increased neuronal activation during CO2
      stimulated breathing (CO2-SB) in awake man. 2. Five male volunteers were scanned
      during CO2-SB (mean +/- S.E.M.; end-tidal PCO2, 50.3 +/- 1.7 mmHg; respiratory
      frequency, 16.4 +/- 2.7 min-1; tidal volume, 1.8 +/- 0.2 l). As control, scans
      were performed during 'passive' isocapnic (elevated fraction of inspired CO2)
      positive pressure ventilation (end-tidal PCO2, 38.4 +/- 1.0 mmHg; respiratory
      frequency, 15.5 +/- 2.2 min-1; tidal volume, 1.6 +/- 0.2 l). With CO2-SB, all
      subjects reported dyspnoea. 3. The anatomical locations of the increases in
      relative rCBF (CO2-SB versus control) were obtained using magnetic resonance
      imaging. 4. Group analysis identified neuronal activation within the upper
      brainstem, midbrain and hypothalamus, thalamus, hippocampus and parahippocampus,
      fusiform gyrus, cingulate area, insula, frontal cortex, temporo-occipital cortex
      and parietal cortex. No neuronal activation was seen within the primary motor
      cortex (at sites previously shown to be associated with volitional breathing). 5.
      These results suggest neuronal activation within the limbic system; this
      activation may be important in the sensory and/or motor respiratory responses to
      hypercapnia in awake man.

PMID- 8568668
TI  - Paired-pulse modulation of fast excitatory synaptic currents in microcultures of
      rat hippocampal neurons.
AB  - 1. Paired-pulse modulation of excitatory non-N-methyl-D-aspartate (non-NMDA)
      receptor-mediated autaptic currents and conventional monosynaptic (interneuronal)
      excitatory postsynaptic currents (EPSCs) was investigated in microcultures of rat
      hippocampal neurons, where polysynaptic influences are eliminated. 2. Most
      autaptic currents and EPSCs exhibited paired-pulse depression in response to
      paired stimuli. Depression was sensitive to the level of transmitter release,
      which was varied by manipulating extracellular Ca2+ and Mg2+ concentrations.
      Paired-pulse facilitation emerged in many cells at low levels of transmitter
      release. 3. Paired-pulse depression and facilitation could be differentially
      expressed at two distinct postsynaptic targets of a single presynaptic cell, and
      the form of modulation was not dependent upon the transmitter phenotype of the
      postsynaptic cell. 4. Paired-pulse depression recovered exponentially with a time
      constant of approximately 5 s, although in most neurons a much faster component
      of recovery was detected. Recovery from paired-pulse facilitation was well
      described by a single exponential of 380 +/- 57 ms. 5. Under conditions of robust
      paired-pulse depression of evoked responses, spontaneous autaptic and
      postsynaptic currents (sEPSCs, presumed miniature EPSCs) occurred at an enhanced
      frequency immediately following evoked responses. The decay of the frequency
      increase mirrored the time course of recovery from paired-pulse facilitation of
      evoked responses examined under conditions of reduced transmitter release. 6.
      Several lines of evidence suggested a large presynaptic component to paired-pulse
      depression. In eight out of nine cells no depression in sEPSC amplitudes was
      detected following conditioning stimulation. Simultaneously recorded glial
      glutamate uptake currents showed depression similar to neuronal evoked EPSCs.
      Finally, NMDA receptor-mediated EPSC paired-pulse depression at positive
      potentials was similar to non-NMDA EPSC depression. 7. Neither adenosine nor
      glutamate feedback onto presynaptic receptors is likely to mediate paired-pulse
      depression, because neither competitive nor non-competitive inhibitors of the
      actions of these agents diminished paired-pulse depression.

PMID- 8568670
TI  - The effects of extracellular pH and calcium change on force and intracellular
      calcium in rat vascular smooth muscle.
AB  - 1. In order to investigate the mechanism whereby changes in external pH (pHo)
      alter tone in rat mesenteric resistance vessels, we have made simultaneous
      measurements of tension and intracellular Ca2+ [Ca2+]i. Strips of mesenteric
      artery were loaded with the Ca(2+)-sensitive indicator indo-1 and superfused with
      physiological salt solution at pH 7.4 and 37 degrees C. 2. An increase of pHo
      from 7.4 to 7.9 produced an increase in tension. This was accompanied by an
      increase in [Ca2+]i in resting and high-K(+)-depolarized vessels. Acidification
      to 6.9 reduced tension and was associated with a fall in [Ca2+]i. Over the pHi
      range examined, 6.6-7.9, parallel changes in [Ca2+]i and tension were found in
      K(+)-activated vessels. 3. In contrast to the relatively slow change in [Ca2+]i,
      pHi and tension with change of pHo, depolarization produced rapid changes in
      [Ca2+]i and tension, consistent with a more direct action on Ca2+ mobilization.
      4. Reducing the external [Ca2+] below 1 mM produced a pronounced fall in [Ca2+]i
      and force. Changes in [Ca2+]i, produced by alteration of external [Ca2+] (Cao2+)
      were used to examine the relation between [Ca2+]i and tension. A linear relation
      was found. Alteration of pHo to 6.9 or 7.9 did not significantly change this
      relation. When the tension data were normalized to their own maxima, no shift in
      the tension-Ca2+ relation occurred, suggesting little or no effect of pH on the
      Ca2+ sensitivity of force production by the contractile proteins. 5. To determine
      further whether the changes in [Ca2+]i produced by alteration of pHo could
      account for all the changes observed in tension, [Ca2+]i was restored to control
      levels while maintaining an altered pHo. When this was done, restoration of
      [Ca2+]i led to restoration of force. Thus, in this preparation, the changes in
      [Ca2+]i produced by altering pHo in depolarized vessels can account for the
      changes in vascular tone.

PMID- 8568669
TI  - Control of sarcoplasmic reticulum calcium release during calcium loading in
      isolated rat ventricular myocytes.
AB  - 1. Isolated rat ventricular myocytes were whole-cell voltage clamped using
      electrodes containing fluorescent Ca2+ indicators. Cytosolic [Ca2+] ([Ca2+]i) was
      estimated with calcium green-2 in combination with carboxy SNARF-1 to remove
      movement artifacts, or with indo-1. 2. Sarcoplasmic reticulum (SR) Ca2+ was
      depleted using 20 mM caffeine in Na(+)-containing superfusion solution, and cells
      were Ca2+ loaded by voltage clamp depolarizations applied during superfusion with
      Na(+)-free 2 mM Ca2+ solution. Ca2+ currents (ICa) and fluorescence transients
      elicited by these depolarizations were measured, and the releasable Ca2+ content
      of the Sr was estimated from the amplitude of fluorescence transients elicited by
      the rapid application of 20 mM caffeine. 3. Depolarization-induced [Ca2+]i
      transients increased in amplitude and duration during superfusion with Na(+)-free
      2 mM Ca2+ solution, independent of changes in peak ICa. Caffeine application
      confirmed that the SR Ca2+ content increased during this manoeuvre. 4. With
      increased Ca2+ loading, the fraction of releasable SR Ca2+ involved in
      depolarization-induced transients increased, and the gradation in [Ca2+]i
      transient amplitude produced by beat-to-beat variation of voltage clamp pulse
      duration (10-100 ms) was progressively lost. This duration dependence of [Ca2+]i
      transients was maintained during Ca2+ loading when the Ca2+ buffering capacity of
      the electrode solution was increased with 100 microM BAPTA, 150 microM EGTA, or
      60 microM indo-1. 5. These data suggest that Ca2+ released from the SR during a
      stimulated [Ca2+]i transient promotes further SR Ca2+ release to a degree which
      is smoothly graded with SR Ca2+ content. The effects of exogenous Ca2+ buffers
      suggest that this positive feedback is mediated, at least in part, by [Ca2+]i.

PMID- 8568671
TI  - Extracellular osmotic pressure modulates sodium-calcium exchange in isolated
      guinea-pig ventricular myocytes.
AB  - 1. The sensitivity of the cardiac Na(+)-Ca2+ exchange current to changes in
      osmotic pressure was investigated in guinea-pig ventricular myocytes, using the
      whole-cell patch-clamp technique. 2. A hyposmotic challenge applied by removal of
      sucrose from the standard bathing solution reduced exchanger current, measured as
      the Ni(2+)-sensitive component of whole-cell transsarcolemmal current. These
      changes were fully reversible. 3. No response of whole-cell current to hyposmosis
      was observed when Ca2+ was removed from the bathing solution by chelation with 1
      mM EGTA. 4. Inclusion of 25 microM exchanger inhibitory peptide (XIP) in the
      pipette solution caused a marked reduction in the Ni(2+)-sensitive component of
      membrane current, but the percentage change in Ni(2+)-sensitive membrane slope
      conductance evoked by hyposmosis was the same as when XIP was omitted from the
      pipette solution. 5. Exposure of cells to hyperosmotic solutions produced
      variable responses. In a majority of cells, solutions 30% hyperosmotic compared
      with control evoked a persistent increase in exchanger current, whereas for
      solutions 50% hyperosmotic, a larger but transient increase in current was
      observed. 6. Over a wide range of osmolalities (50-130% of isosmotic) the changes
      in Ni(2+)-sensitive membrane slope conductance were linearly related to the
      changes in extracellular osmotic pressure. 7. We propose that one consequence of
      exposing ventricular myocytes to anisosmotic solutions is modulation of Na(+)
      Ca2+ exchange current.

PMID- 8568672
TI  - Inhibition of calcium currents and exocytosis by Lambert-Eaton syndrome
      antibodies in human lung cancer cells.
AB  - 1. Human small-cell lung cancer (SCLC) cells are believed to express the antigens
      responsible for the production of pathological antibodies in the Lambert-Eaton
      syndrome (LES), a Ca2+ channel disorder in which quantal transmitter release from
      the motor nerve terminal is impaired. Whole-cell patch-clamp techniques were used
      to study the voltage-dependent Ca2+ channels expressed by H146 SCLC cells and the
      effects of LES antibodies on these channels. The types of Ca2+ channels were
      determined using biophysical properties and pharmacological sensitivity to
      several antagonists. 2. Whole-cell Ca2+ currents (ICa) in SCLC cells are
      sensitive to the dihydropyridine (DHP) nicardipine, omega-conotoxin GVIA (omega
      CgTX GVIA) and omega-agatoxin IVA (omega-AgTX IVA). Nicardipine at 100 nM and 10
      microM reduced ICa by 35 and 45% (n = 38 cells), respectively, while omega-CgTX
      GVIA (1 microM) inhibited ICa by 32% (n = 31). Application of omega-AgTX IVA at
      50 and 100 nM to the cancer cells decreased ICa by 41 and 42%, respectively (n =
      22). 3. Measurement of cell membrane capacitance (Cm) revealed that Ca(2+)
      dependent exocytosis underlies the secretory activity of SCLC cells. Exocytosis,
      when induced by step depolarizing pulses and measured by increases in Cm, was
      markedly inhibited by nicardipine (10 microM) and omega-AgTX IVA (100 nM). In
      contrast, omega-CgTX GVIA (1 microM) was not as effective in altering increases
      in Cm. 4. From negative (-80 mV) and depolarized (-40 mV) holding potentials,
      both peak and plateau ICa were inhibited by the presence of LES antibodies (1 mg
      ml-1 IgG). LES serum also reduced depolarization-induced increases in Cm by 48%
      (n = 15). 5. To determine whether the LES antibodies are downregulating a
      specific type(s) of Ca2+ channel, nicardipine (10 microM), omega-CgTX GVIA (1
      microM) or omega-AgTX IVA (100 nM) was applied to tumour cells that had been
      previously exposed to LES serum for 24 h. The most pronounced change was that
      omega-AgTX IVA was 38-84% less effective at reducing ICa after the IgG treatment.
      The effectiveness of nicardipine was diminished by 18% after incubation with the
      LES antibodies, whereas the omega-CgTX GVIA was seen to be more effective. These
      results suggest that LES IgG downregulates P-type Ca2+ channels and, possibly, to
      a lesser extent L-type channels. 6. In view of recent evidence that P-type Ca2+
      channels mediate cholinergic transmitter release at the mammalian neuromuscular
      junction (NMJ), the expression of P-type Ca2+ channels in the SCLC cells and the
      reactivity of LES IgG with these channels support the hypothesis that P-type Ca2+
      channels in these cancer cells may trigger the autoantibody production in this
      disorder. The antibodies so produced are implicated in the functional impairment
      of the Ca2+ channels characteristic of LES.

PMID- 8568673
TI  - Characterization of an ATP-modulated large conductance Ca(2+)-activated K+
      channel present in rat cortical neurones.
AB  - 1. Single channel current recordings were used to study the characteristics of a
      large conductance Ca(2+)-activated K+ (BKCa) channel present in neurones acutely
      dissociated from the rat motor cortex. Application of ATP to the intracellular
      surface of excised inside-out patches produced a large, concentration-dependent
      increase in BKCa channel activity. 2. This ATP-mediated activation was dependent
      upon the presence of Mg2+ in the intracellular bathing solution and was
      diminished by the phosphatases 2,3-butanedione monoxime (BDM) or alkaline
      phosphatase and by the protein kinase inhibitors staurosporine, H-7 and PKI. 3.
      ADP stimulated BKCa channel activity in a Mg(2+)-dependent manner, an action also
      inhibited by the concomitant application of PKI or BDM. The effect of ADP was
      reduced by application of hexokinase and glucose or by application of the
      adenylate kinase inhibitor Ap5A. 4. Of other nucleotides tested, only CTP
      consistently activated BKCa channel activity. 5. Using the cell-attached
      configuration, bath application of forskolin or dibutyryl cAMP stimulated BKCa
      channel activity. 6. It is concluded that BKCa channel activity in the rat motor
      cortex is subject to modulation by the activity of a closely associated kinase.
      The ability of cAMP activators to stimulate BKCa channel activity in the intact
      cell suggests that this system may be of physiological importance.

PMID- 8568674
TI  - A rapidly activating type of outward rectifier K+ current and A-current in rat
      suprachiasmatic nucleus neurones.
AB  - 1. The properties of calcium-independent (i.e. persisting in the absence of
      external calcium) depolarization-activated potassium currents in suprachiasmatic
      nucleus (SCN) neurones (n = 75) were studied under voltage-clamp conditions with
      whole-cell patch-clamp recordings in rat hypothalamic slices (150-175 microns).
      2. Two distinct types of potassium currents were found. One was a rapidly
      activating and slowly inactivating type of outward rectifier (named IK(FR) for
      fast rectifier potassium current), similar to a potassium current described in
      cardiac muscle, and the other was a transient A-current (IA). 3. The rates of
      activation and deactivation of IK(FR) were voltage dependent. Time constants of
      activation fitted to n4 kinetics and declined from 3.5 ms (at -20 mV) to 1.1 ms
      (at 60 mV). Inactivation had a biexponential time course with voltage-independent
      time constants of 0.3 s (minor component) and 3.0 s (major component) between 10
      and 50 mV. IK(FR) was activated above -40 mV with a V1/2 (membrane potential at
      half-maximal activation) of 14 +/- 2 mV and slope factor of -17 +/- 1 mV reaching
      a conductance (not maximal) of 10.8 +/- 1.7 nS at 60 mV. Steady-state
      inactivation had a slope factor of 11 +/- 1 mV. 4. IK(FR) was highly selective
      for K+ (PNa/PK = 0.002). Tetraethylammonium (TEA) reduced IK(FR) reversibly (IC50
      = 20 mM), while 4-aminopyridine (4-AP) at 10 mM had little effect. The remaining
      current in 30 mM TEA was similar to that in control conditions, indicating that
      TEA reduced IK(FR) rather than revealed an additional TEA-resistant current. 5.
      The rate of IA activation was voltage dependent with time to peak declining from
      8.5 ms (at -40 mV) to 3.6 ms (at 60 mV). Inactivation had a biexponential time
      course with voltage-dependent and voltage-independent time constants. The two
      components were similar in amplitude. IA was activated above -60 mV, reaching a
      maximal conductance of 3.6 +/- 0.4 nS at above 20 mV. Steady-state inactivation
      was complete above -10 mV. Rates of onset of inactivation (at -40 mV) and
      recovery from inactivation (at -100 mV) were similar with time constants of 39 +/
      5 and 41 +/- 9 ms, respectively. 6. IK(FR) and IA were found in every neurone
      tested in the SCN and in all locations throughout the nucleus. The possible
      function of these currents is discussed, particularly in relation to the
      circadian rhythm of firing rate in the SCN.

PMID- 8568675
TI  - Functional role of follicular cells in the generation of osmolarity-dependent Cl-
      currents in Xenopus follicles.
AB  - 1. Osmolarity-dependent (osmo-dependent) ionic currents from follicle-enclosed
      Xenopus oocytes (follicles) were studied using the two-microelectrode voltage
      clamp technique, combined with intra-oocyte pressure injection of sucrose or
      polyethylene glycols (PEGs). 2. Intra-oocyte injections of sucrose or PEG (3-25
      nmol) generated inward membrane currents (follicles held at -60 mV) associated
      with an increase in membrane conductance. These currents were carried mainly by
      chloride ions (ICl(osm)), and were strongly attenuated by increasing the tonicity
      of the external medium, or by external application of La3+ (0.1-1 mM). 3. The
      ability to generate ICl(osm) depended on the molecular weight of the injected
      PEG. Injections of PEG 200 or 300 generated ICl(osm) in 95% of the follicles
      tested, PEG 600 generated comparable currents in only 20% of the follicles, while
      similar injections of PEG 1000 did not elicit ICl(osm). 4. Octanol (1-1.5 mM), a
      gap junction channel blocker, reversibly inhibited 50-90% of the ICl(osm)
      generated by injections of sucrose or PEG 300. Moreover, sucrose or PEG
      injections did not elicit ICl(osm) in defolliculated oocytes. 5. It is concluded
      that an increase in the internal osmolarity of the follicular cells activates a
      mechanism, probably involving cellular swelling, which leads to the opening of
      ICl(osm) channels most probably located in the follicular cell membrane.

PMID- 8568676
TI  - Cyclic AMP prevents activation of a swelling-induced chloride-sensitive
      conductance in chick heart cells.
AB  - 1. Changes in myocardial cell volume and whole-cell currents were measured
      simultaneously during hyposmotically induced cell swelling. In the conventional
      patch clamp configuration, hyposmotic challenge caused myocytes to swell
      continuously and was associated with the development of a sustained, swelling
      induced chloride conductance (ICl). In contrast, perforated patch-clamped
      myocytes demonstrated regulatory volume decreases (RVD) during hyposmotic
      challenge, and ICl was not generated. 2. The swelling-induced ICl in
      conventionally patch-clamped myocytes was inhibited by application of forskolin
      (15 microM) and was prevented when the pipette filling solution contained cAMP
      (10 microM) and isobutylmethylxanthine (IBMX, 1 mM). ICl could also be prevented
      by inhibition of protein phosphatase activity, using okadaic acid (100 nM).
      Conversely, a swelling-induced current could be generated in myocytes under
      perforated patch clamp by inhibition of protein kinase A, using the antagonist Rp
      cAMPS (10 microM). These data demonstrate that cAMP-dependent protein
      phosphorylation is both necessary and sufficient to prevent development of ICl
      during cell swelling. 3. Unlike other chloride currents described previously in
      heart muscle, generation of the novel swelling-induced ICl requires
      dephosphorylation of a cAMP-dependent protein phosphorylation site; hence it can
      be prevented by stimulation of cAMP-dependent protein phosphorylation or by
      inhibition of protein phosphatase activity.

PMID- 8568677
TI  - Depolarizing GABA-activated Cl- channels in embryonic rat spinal and olfactory
      bulb cells.
AB  - 1. We have compared the electrical properties of the Cl- channels activated by
      GABA in cells acutely dissociated from embryonic (E) spinal cord (SC) and
      olfactory bulb (OB) regions at E15 using different configurations of the patch
      recording technique. By in situ analysis these cells express GABAA receptor mRNAs
      encoding a common set of subunits (alpha 2, beta 2, and beta 3). SC cells also
      express alpha 3, alpha 5 and gamma 2s transcripts. 2. Whole-cell recordings
      revealed current responses to GABA (0.5 microM to 1 mM) in 242 out of 294 cells.
      In both SC and OB cells, currents evoked by 2 microM GABA could be potentiated by
      diazepam (DZP) in a dose-dependent manner with an EC50 of approximately 50 nM in
      both SC and OB. The maximal effect was approximately 300%. Both SC and OB cells
      exhibited GABA-activated currents that were only partially sensitive to zinc even
      at high micromolar concentrations. The effect of DZP and the relatively modest
      sensitivity to zinc suggest the presence of gamma subunits in both preparations.
      3. Spectral analysis of current responses in twenty-six cells showed that power
      spectra could be fitted by three exponential components (tau 1-3) in the cells of
      both areas. The tau of the longest-lasting component (tau 3) was significantly
      different in the cells of the two areas: approximately 50 ms in OB and 80-100 ms
      in SC. No statistically significant differences in the average inferred unitary
      conductance between the two cell types could be resolved. 4. Single-channel
      properties were examined directly using the cell-attached configuration. GABA
      activated channels could be recorded in only 89 out of well-sealed 984 patches
      and most of them exhibited multiple channel activity. The mean open time in the
      response to 10 microM GABA was significantly shorter in OB cells (12 ms) compared
      to SC cells (25 ms) while the average conductance values were not significantly
      different between the two cell types. 5. On average, Cl- channels reversed
      polarity when the on-cell patch pipette potential was approximately -30 mV. Thus,
      in these embryonic neurons, micromolar GABA activates Cl- channels, which, when
      open, effectively depolarize cells by approximately 30 mV. 6. Cl- channels
      activated by GABA are open longer in embryonic SC cells than in OB cells. This
      statistically significant difference in native GABAA receptor Cl- channel
      properties correlates with, and may be related to differences in subunit mRNA
      expression.

PMID- 8568678
TI  - Pre- and postsynaptic glutamate receptors at a giant excitatory synapse in rat
      auditory brainstem slices.
AB  - 1. Whole-cell patch recordings were used to examine the EPSC generated by the
      calyx of Held in neurones of the medial nucleus of the trapezoid body (MNTB).
      Each neurone receives a somatic input from a single calyx (giant synapse). 2. A
      slow NMDA receptor-mediated EPSC peaked in 10 ms and decayed as a double
      exponential with time constants of 44 and 147 ms. A fast EPSC had a mean rise
      time of 356 microseconds (at 25 degrees C), while the decay was described by a
      double exponential with time constants of 0.70 and 3.43 ms. 3. Cyclothiazide
      slowed the decay of the fast EPSC, indicating that it is mediated by AMPA
      receptors. The slower time constant was slowed to a greater extent than the
      faster time constant. Cyclothiazide potentiated EPSC amplitude, partly by a
      presynaptic mechanism. 4. The metabotropic glutamate receptor (mGluR) agonists,
      1S,3S-ACPD, 1S,3R-ACPD and L-2-amino-4-phosphonobutyrate (L-AP4) reversibly
      depressed EPSC amplitude. A dose-response curve for 1S,3S-ACPD gave an EC50 of 7
      microM and a Hill coefficient of 1.2. 5. Analysis of the coefficient of variation
      ratio showed that the above mGluR agonists acted presynaptically to reduce the
      probability of transmitter release. Adenosine and baclofen also depressed
      transmission by a presynaptic mechanism. 6. alpha-Methyl-4-carboxyphenylglycine
      (MCPG; 0.5-1 mM) did not antagonize the effects of 1S,3S-ACPD, while high
      concentrations of L-2-amino-3-phosphonopropionic acid (L-AP3; 1 mM) and 4-carboxy
      3-hydroxyphenyglycine (4C3HPG; 500 microM) depressed transmission. 7. There was a
      power relationship between [Ca2+]o and EPSC amplitude with co-operativity values
      ranging from 1.5 to 3.4. 8. The mechanism by which mGluRs modulate transmitter
      release appeared to be independent of presynaptic Ca2+ or K+ currents, since ACPD
      caused no change in the level of paired-pulse facilitation or the duration of the
      presynaptic action potential (observed by direct recording from the terminal),
      indicating that the presynaptic mGluR transduction mechanism may be coupled to
      part of the exocytotic machinery. 9. Our data are not consistent with the
      presence at the calyx of Held of any one known mGluR subtype. Comparison of the
      time course and pharmacology of the fast EPSC with data from cloned AMPA
      receptors is consistent with the idea that GluR-Do subunits dominate the
      postsynaptic channels.

PMID- 8568679
TI  - Temperature effects on membrane potential and input resistance in rat
      hypothalamic neurones.
AB  - 1. Whole-cell recordings were conducted in rat hypothalamic tissue slices to test
      the hypothesis that thermal changes in membrane potential contribute to neuronal
      thermosensitivity. Intracellular recordings of membrane potential and input
      resistance were made in eighty-two neurones, including twenty-four silent
      neurones and fifty-eight spontaneously firing neurones (22 warm-sensitive
      neurones and 36 temperature-insensitive neurones). Fifty-seven of the neurones
      were recorded in the preoptic and anterior hypothalamus. 2. Warm-sensitive
      neurones increased their firing rates during increases in temperature (1.07 +/-
      0.06 impulses s-1 degree C-1), but their resting membrane potentials were not
      affected by temperature (0.06 +/- 0.06 mV degree C-1). Similarly, temperature did
      not affect the membrane potentials of temperature-insensitive neurones or silent
      neurones. 3. Silent neurones had significantly lower input resistances (256.9 +/-
      20.0 M omega), compared with temperature-insensitive (362.6 +/- 57.2 M omega) and
      warm-sensitive neurones (392.2 +/- 50.0 M omega). Temperature had the same effect
      on all three types of neurones, such that resistance increased during cooling and
      decreased during warming. 4. If hyperpolarizing or depolarizing holding currents
      were applied to neurones, temperature caused changes in the membrane potentials.
      This spurious effect can be explained by thermally induced changes in the input
      resistance. 5. Measurements of electrode tip potentials indicated that artificial
      changes in membrane potential may also be recorded if grounding electrodes are
      not isolated from the changes in temperature. 6. These results suggest that
      physiological changes in resting membrane potentials do not determine neuronal
      warm sensitivity, and thermal changes in input resistance do not determine the
      primary differences between warm-sensitive and temperature-insensitive
      hypothalamic neurones.

PMID- 8568680
TI  - Perinatal development of action potential propagation in cat rubrospinal axons.
AB  - 1. The development of action potential conduction was studied by intracellular
      recording of antidromic spikes in cat rubrospinal cells. 2. The distance between
      the C1 and L1 spinal segments increased linearly from 5.6 cm at embryonic day (E)
      59 to 9.8 cm at postnatal day (P) 30. 3. The conduction time from the C1 segment
      to the rubrospinal neuron soma, estimated from antidromic spike latency evoked by
      stimulation of the C1 segment, decreased rapidly prior to birth and then slowly
      thereafter. This coincided with a reduction in conduction time variation between
      cells. 4. The conduction time from the red nucleus to the L1 segment followed a
      similar time course during development. The conduction time reached the adult
      value by P30, at which time the spinal cord is only half the adult length. 5. The
      conduction velocity between the C1 and L1 segments increased monotonically
      between E59 and P30, from a low of 1 m s-1 to a maximum of 34 m s-1. 6. The rise
      time of rubrospinal neuron somadendritic spikes followed a developmental time
      course similar to that for conduction time. 7. Myelination of rubrospinal axons,
      as judged by the presence of myelinated segment spikes, began to occur prior to
      E59. 8. These findings suggest that development of action potential propagation
      in rubrospinal cells can be divided into an early and a late stage: conduction
      time reaches the adult value during the early stage, i.e. by the first postnatal
      month, and is maintained during the late stage. We propose that myelination, axon
      diameter increase and maturation of membrane properties act to reduce conduction
      time to adult values during the early stage, while a proportional increase in
      fibre diameter with axonal length results in a constant conduction time during
      the late stage.

PMID- 8568681
TI  - Transcellular gaps in microvascular walls of frog and rat when permeability is
      increased by perfusion with the ionophore A23187.
AB  - 1. The experiments described in this paper aimed to determine whether the gaps
      which develop in microvascular endothelium in association with increases in
      permeability are located in the intercellular clefts or are openings passing
      through the endothelial cells. 2. Hydraulic permeability (Lp) was estimated in
      frog mesenteric capillaries and single rat venules using a microperfusion-micro
      occlusion technique before and during perfusion with solutions containing the
      ionophore A23187 at a concentration of 10 microM. When Lp was seen to have
      increased, the tissues were fixed in situ with 2.5% glutaraldehyde. 3. The
      increases in Lp varied considerably from vessel to vessel. In six frog vessels Lp
      increased from 2.6 +/- 0.9 x 10(-7) to 266 +/- 159 x 10(-7) cm s-1 cmH2O-1 and in
      three rat venules Lp rose from 0.94 +/- 0.09 x 10(-7) to 16.4 +/- 4.9 x 10(-7) cm
      s-1 cmH2O-1 (means +/- S.E.M.). 4. Forty openings or gaps were completely
      reconstructed from electron micrographs of serial ultrathin sections of the six
      frog vessels. Thirty-nine of these gaps passed through the endothelial cells and
      did not communicate with the intercellular clefts; one was intercellular.
      Similarly, fifteen out of sixteen gaps reconstructed from electron micrographs of
      the rat venules were transcellular and clearly separated from the intercellular
      clefts. 5. The increased Lp and associated ultrastructural changes induced by
      A23187 were reversed by perfusion with ionophore-free solutions.

PMID- 8568682
TI  - Developmental changes in blood-brain barrier potassium permeability in the rat:
      relation to brain growth.
AB  - 1. The potassium permeability of the blood-brain barrier (BBB) was determined in
      anaesthetized rats aged between 21 days gestation and adult using 86Rb+ as a
      marker for potassium. 2. The brain influx rate constant for 86Rb+ was high in
      fetal cortex at 21 days gestation (42.5 +/- 4.3 microliters g-1 min-1) but had
      decreased markedly by just after birth (12.2 +/- 0.6 microliters g-1 min-1).
      There was a further, gradual, postnatal decline to 7.0 +/- 0.3 microliters g-1
      min-1 by 50 days after birth. 3. Developmental changes in passive BBB
      permeability were examined over the same age range using 14[C]urea. These studies
      showed similar developmental changes in influx rate to those found for 86Rb+.
      Specifically, a marked perinatal decline followed by a more gradual postnatal
      fall. Thus, the changes in potassium permeability probably reflect a decrease in
      the BBB paracellular leak during development. 4. The changes in BBB permeability
      coincide with changes in the rate of brain growth and the associated rate of
      brain potassium accumulation. As the potassium permeability properties of the
      adult BBB would provide insufficient potassium influx to meet the requirement
      associated with fetal brain growth, it is suggested that need for potassium may
      be the reason for the greater BBB permeability early in development.

PMID- 8568683
TI  - Maturation of rat renal phosphate transport: effect of triiodothyronine.
AB  - 1. Prevention of weaning prevents the increase in the carrier affinity for Na(+)
      cotransported phosphate (Pi) and the normal elevation of plasma 3,5,3'
      triiodothyronine (T3) which occur between postnatal days 14 and 21. 2. This study
      examines the possible role of T3 in the control of the maturation process of Pi
      transport. Clearance experiments and brush-border membrane studies were performed
      on 14-day-old rats given T3. 3. The fractional excretion of Pi of T3-treated rats
      was 33% lower compared with controls (P < 0.01). After Pi perfusion, it remained
      at a lower level, and the amount of Pi reabsorbed per minute, corrected for the
      glomerular filtration rate (RPi/GFR), was higher. 4. The membrane vesicles from
      14-day-old rats given T3 showed a 30% increase in carrier affinity for Na(+)
      cotransported Pi. In addition to this maturational effect of T3, a 46% increase
      in Vmax was also observed. 5. The amount of immunoreactive Pi transporter,
      detected using anti-(NaPi-2) antiserum, was increased in T3-treated rats. 6.
      Glucose transport, another Na(+)-dependent transport system, was not altered by
      T3. 7. It is concluded that exogenous T3 given before the third postnatal week
      specifically induced precocious maturation of renal Pi transport in 14-day-old
      rats, suggesting that thyroid hormone is normally involved in this maturation.

PMID- 8568684
TI  - Injury to muscle fibres after single stretches of passive and maximally
      stimulated muscles in mice.
AB  - 1. Our purpose was to investigate the initial mechanisms responsible for
      contraction-induced injury. Most studies of mechanisms of contraction-induced
      injury have been based on observations made either shortly after many repeated
      contractions at the peak of fatigue, or days after, at the peak of delayed onset
      injury. As a result, conclusions based on these studies are complicated by
      interactions of mechanical and biochemical events, as well as the passage of
      time. We studied the initial mechanical events associated with contraction
      induced injury immediately following single stretches of whole skeletal muscles
      of mice in situ. 2. We tested the hypothesis that immediately following a single
      stretch, the severity of contraction-induced injury is a function of both strain
      and average force. Consequently, the work done to stretch the muscle would be the
      best predictor of the magnitude of injury. Extensor digitorum longus muscles were
      adjusted to optimum length for force (L(o)). Passive (not stimulated) and
      maximally activated muscles were exposed to single stretches of 10, 20, 30, 50 or
      60% strain, relative to muscle fibre length (Lf), at a rate of 2 Lf s-1. 3. The
      magnitude of injury was represented by the force deficit 1 min after the stretch
      expressed as a percentage of the maximum force prior to the stretch. The
      occurrence of injury was confirmed directly by electron microscopic analysis of
      the ultrastructure of muscle fibres that were fixed immediately following single
      stretches. 4. For active muscles, a single stretch of only 30% strain produced a
      significant force deficit, whereas for passive muscles, a larger strain was
      required. Stretches of greater than 50% strain resulted in greater force deficits
      for passive than for maximally activated muscles. For either condition, the work
      done to stretch the muscle was the best predictor of the magnitude of injury,
      accounting for 76% of the variability in the force deficit for maximally
      activated muscles, and 85% for passive muscles.

PMID- 8568685
TI  - Some effects of vagal blockade on abdominal muscle activation and shortening in
      awake dogs.
AB  - 1. The mechanisms of abdominal muscle activation are thought to be different
      during expiratory threshold loading (ETL) compared with hypercapnia. Our
      objectives in the present study were to determine the effects of removing
      excitatory vagal feedback on abdominal muscle activation, shortening and pattern
      of recruitment during ETL and hypercapnia. Six tracheotomized dogs were
      chronically implanted with sonomicrometer transducers and fine wire EMG
      electrodes in each of the four abdominal muscles. Muscle length changes and EMG
      activity were studied in the awake dog during ETL (6 dogs) and CO2 rebreathing (3
      dogs), before and after vagal blockade. 2. Following vagal blockade, the change
      in volume (increase in functional residual capacity, FRC) during ETL was greater
      and active phasic shortening of all the abdominal muscles was reduced, when
      shortening was compared with a similar change in lung volume. Similarly, at
      comparable minute ventilation, abdominal muscle active shortening was also
      reduced during hypercapnia. The internal muscle layer was recruited
      preferentially in both control and vagally blocked dogs during both ETL and
      hypercapnia. 3. The degree of recruitment of the abdominal muscles during ETL and
      hypercapnia in awake dogs is influenced by vagal feedback, but less so than in
      anaesthetized dogs. These results illustrate the importance of the vagi and
      abdominal muscle activation in load compensation. However, vagal reflexes are
      apparently not contributing to the preferential recruitment of the internal
      muscle layer. In awake dogs during vagal blockade abdominal muscle recruitment
      still occurs by extravagal mechanisms.

PMID- 8568686
TI  - Effects of age on aneural regeneration of soleus muscle in rat.
AB  - 1. The ability of autografted soleus muscles to regenerate without innervation
      was investigated in young (two groups: 17 days or 35 g and 5 weeks or 100 g) and
      old (10 weeks or 300 g and 19 months or 700 g) rats. 2. Tetanic force and fibre
      area of the regenerated muscles were followed in 35, 100 and 300 g rats and found
      to reach a maximum 10-15 days after the operation and then declined. 3. Maximal
      tetanic force and fibre area were greater in old than in young rats; the largest
      increase was seen between 100 and 300 g rats. The relaxation phase of the twitch
      became shorter in the 700 g animals. The force per cross-sectional area appeared
      to fall with age. The length of the new fibres, inferred from the width of the
      length-force curve, increased only slightly with age. 4. Ten days after grafting,
      autophagocytosis of necrotic fibres was completed in young but not in old rats.
      The new fibres in young rats had one central nucleus per cross-section and fibre
      size was unimodally distributed; fibres in old rats had multiple internal nuclei
      and the size distribution was bimodal due to the presence of large fibres. 5.
      Previous results indicating greater muscle regeneration in young than in old rats
      may reflect more vigorous reinnervation in young animals rather than a greater
      myogenic potential. Increased fibre size of regenerated muscles of old compared
      with young rats may be attributed to the larger amount of necrotic material which
      is mitogenic for satellite cells, or to age-dependent changes of the expression
      of cell adhesion molecules. Enhanced lateral fusion of myotubes would give rise
      to large fibres with multiple internal nuclei.

PMID- 8568687
TI  - Expression of immediate early genes in rat gastric myenteric neurones: a
      physiological response to feeding.
AB  - 1. Expression of the immediate early genes c-fos, c-jun and c-myc in rat stomach
      in response to feeding and gastric distension was examined by Northern blot
      analysis and in situ hybridization. 2. Refeeding of fasted rats induced a
      transient increase in c-fos mRNA abundance in gastric corpus and antrum that was
      sixfold within 15 min and declined within 4 h. The response was not mediated by
      gastrinergic or muscarinic cholinergic mechanisms; it was reduced but not
      abolished by hexamethonium. No changes in expression of c-jun, c-myc or the
      constitutively expressed protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      were observed. 3. In conscious rats prepared with a gastric fistula, gastric
      distension with nutritive and non-nutritive solutions at a physiological pressure
      for 30 min induced expression of c-fos, c-jun and c-myc, but not GAPDH. 4.
      Messenger RNA encoding c-fos was localized by in situ hybridization to gastric
      myenteric neurones of animals that underwent gastric distension, but not of
      undistended controls. 5. The results suggest that expression of c-fos in gastric
      myenteric neurones is an early response to the physiological stretching of the
      stomach wall that accompanies feeding. With supraphysiological distension, other
      immediate early genes may be recruited.

PMID- 8568688
TI  - The mechanism of inhibitory action of secretin on gastric acid secretion in
      conscious rats.
AB  - 1. Secretin has been recognized as an important enterogastrone. In order to
      investigate the mechanism of secretin-induced inhibition of gastric acid
      secretion, the effects of both anti-somatostatin antibody and indomethacin on
      acid secretion were examined in conscious rats with gastric cannulas. 2. Secretin
      given intravenously at 5.6 pmol kg-1 h-1 inhibited profoundly the acid secretion
      stimulated by pentagastrin at 0.3 microgram kg-1 h-1. 3. When a rabbit
      antisomatostatin serum was given intravenously, it not only abolished the
      secretin-induced inhibition on the pentagastrin-stimulated acid secretion, but
      also augmented both basal and pentagastrin-stimulated acid secretion. 4.
      Indomethacin also significantly augmented basal acid secretion, starting 45 min
      after the drug delivery began. It reversed the secretin-induced inhibition but it
      did not augment the pentagastrin-stimulated acid secretion. 5. Neither
      antisomatostatin serum influenced prostaglandin E2-induced inhibition of the
      pentagastrin-stimulated acid secretion, nor did indomethacin affect the
      inhibition by somatostatin, suggesting strongly that the inhibition by
      somatostatin is not mediated by endogenous prostaglandins, nor is that by
      prostaglandins E2 mediated by endogenous somatostatin. 6. It is concluded that
      the inhibitory action of secretin on pentagastrin-stimulated gastric acid
      secretion is mediated by both somatostatin and prostaglandins in conscious rats.
      The two inhibitors do not seem to interact endogenously for the inhibition of
      acid secretion. While endogenous somatostatin exerts a tonic inhibitory effect on
      both basal and pentagastrin-simulated acid secretion, prostaglandins augment
      basal acid secretion only.

PMID- 8568689
TI  - Atrial natriuretic factor release during pregnancy in rats.
AB  - 1. We investigated the control of atrial natriuretic factor (ANF) secretion
      during pregnancy. 2. Plasma ANF levels were measured in conscious virgin female
      rats under basal conditions, and after atrial distension with an indwelling
      balloon catheter. The rats were then mated, and the measurements repeated at 7,
      14 and 21 days of pregnancy, and at 1 week postpartum. Plasma ANF levels were
      also measured in ovariectomized rats injected with progesterone, oestradiol, or
      oestradiol plus progesterone. 3. Basal plasma ANF levels were elevated at 7 and
      14 days of pregnancy, but returned to prepregnant levels by 21 days. At 1 week
      postpartum, they were again elevated. 4. In response to atrial stretch, plasma
      ANF increased significantly in virgin rats (from 100 +/- 10 to 148 +/- 13 pg ml
      1, P < 0.001, n = 20). In contrast, there was no such secretory response observed
      in the pregnant and postpartum animals i.e. stretch-induced secretion of ANF was
      markedly attenuated. 5. Treatment with exogenous oestradiol caused a significant
      increase in plasma ANF levels in acyclic rats. However, neither progesterone nor
      a combination of oestradiol plus progesterone had any effect. 6. It is concluded
      that basal and stretch-induced ANF secretion are differentially influenced by
      pregnancy; oestradiol is identified as a potential stimulatory factor.

PMID- 8568690
TI  - The effects of anaemia on heart, placenta and body weight, and blood pressure in
      fetal and neonatal rats.
AB  - 1. Reports that maternal anaemia in pregnancy is associated with a greater
      placental: birth weight ratio, which predisposes towards high postnatal blood
      pressure in the human, led us to examine the effects of maternal anaemia during
      pregnancy on placental size, fetal and neonatal growth, and blood pressure
      development in the rat. 2. Nutritional anaemia was induced in female rats prior
      to mating and maintained throughout pregnancy and up until weaning of the pups.
      Fetuses were studied at 20 days of gestation (E20). Pups were studied on
      postnatal days 20 (P20) and 40 (P40), having been weaned onto normal rat chow at
      21 days. 3. In the anaemic group placental: fetal body weight ratios were lower
      compared with controls. Body weights at all ages were lower in the anaemic group
      than in controls, despite a greater rate of growth in the anaemic group between
      P20 and P40. 4. At P20 heart weights of the anaemic group were almost twice that
      of controls, suggesting an alteration in their cardiovascular development.
      However, paradoxically, the systolic blood pressure of the anaemic group was
      lower than that of controls. 5. By P40 the systolic blood pressure of the anaemic
      group (136 +/- 3 mmHg) had increased and was greater than that in control pups
      (126 +/- 3 mmHg). 6. In conclusion, we have shown that there is a pronounced
      postnatal rise in systolic blood pressure associated with maternal anaemia during
      pregnancy, which is not related to a greater placental: birth weight ratio.
      Before weaning, anaemic pups have a lower systolic blood pressure than controls
      and there is an important association between the rate of postnatal growth and
      blood pressure.

PMID- 8568691
TI  - Facilitation of the arterial baroreflex by the preoptic area in anaesthetized
      rats.
AB  - 1. Activation of cell bodies in the ventrolateral part of the midbrain
      periaqueductal grey matter (PAG) facilitates the arterial baroreflex via the
      nucleus raphe magnus. The facilitatory effects of stimulation within the
      hypothalamus on the arterial baroreflex and their relation to the PAG and nucleus
      raphe magnus were studied in urethane- and chloralose-anaesthetized rats. 2.
      Systematic mapping experiments revealed that the preoptic area (POA) is the
      principal location in the hypothalamus of neuronal cell bodies that are
      responsible for the potentiation of the baroreflex. In addition to provoking
      hypotension and vagal bradycardia, both electrical and chemical stimulation of
      the POA produced facilitation of baroreflex vagal bradycardia (BVB) that was
      evoked by electrical stimulation of the aortic depressor nerve. Baroreflex
      hypotension was slightly augmented during activation of the POA in vagotomized
      rats. 3. Selective destruction of cell bodies either in the ventrolateral PAG or
      in the nucleus raphe magnus reduced facilitation of BVB by the POA. Hypotension
      and bradycardia due to POA stimulation were also markedly attenuated after such
      selective destruction. 4. In conclusion, the POA, the ventrolateral PAG and the
      nucleus raphe magnus constitute a functional complex that produces cardiovascular
      trophotropic effects including hypotension, vagal bradycardia and baroreflex
      facilitation.

PMID- 8568693
TI  - [Instruments used for measurement of intracellular calcium ions].

PMID- 8568692
TI  - Motor co-ordinates in primate red nucleus: preferential relation to muscle
      activation versus kinematic variables.
AB  - 1. Magnocellular red nucleus (RNm) neurones (n = 158) were recorded from two
      macaque monkeys during a tracking task using one of six single-degree-of-freedom
      manipulanda. This task allowed us to study discrete movements about most of the
      joints of the arm. Single-unit, kinematic and electromyographic (EMG) signals
      from ten to twenty muscles of the upper limb were collected for approximately 2
      min while the monkey used a given manipulandum. Movements about different joints
      were studied by switching among manipulanda. 2. Cross-correlation functions were
      calculated between RNm discharge rate and the kinematic variables, position and
      velocity, and between RNm and each of the EMG signals. Statistically significant
      cross-correlation peaks were found in 24% of the position correlations, 22% of
      the velocity correlations and 32% of the EMG correlations. The highest
      correlations were for EMG, reaching above 0.60. The peak correlation provided an
      effective means of identifying neurones with strong functional relations to one
      or more movements and/or muscles. These could then be analysed in detail, on a
      trial-by-trial basis. 3. The similarity between the dynamics of EMG and velocity
      signals of many highly practised movements makes it difficult to determine which
      might be the more likely target of RNm control. Therefore, we sought exceptions
      to this pattern, in order to distinguish between these two possible modes of
      control. For example, at the end of a movement, muscles occasionally remained
      active as velocity approached zero. Small corrective movements were often
      accompanied by a disproportionately large EMG. During these periods, RNm activity
      usually followed the time course of one or more of the EMG signals as opposed to
      the velocity signal. In the majority of cases, RNm responses were bidirectional,
      less frequently unidirectional and rarely reciprocal. These patterns were similar
      to the patterns of muscle activity. They did not resemble the velocity signals
      unless the latter were passed through a rectifier. 4. The results support the
      hypothesis that the red nucleus generates motor commands in a muscle-based co
      ordinate system. Covariation between RNm discharge and velocity may result
      indirectly from correlations between muscle activation and movement. We discuss
      how the cerebellar cortex might convert the distributed representation of target
      position, known to be present in the posterior parietal cortex, directly into
      dynamic, muscle-based commands in the rubro-cortico-cerebellar limb premotor
      network.

PMID- 8568694
TI  - [Effect of weightlessness simulation on skeletal muscle histochemistry and bone
      metabolism of spontaneously hypertensive rats].

PMID- 8568695
TI  - Blowing the whistle on health care fraud: the expanding role of nurses in helping
      the government combat health care fraud.

PMID- 8568696
TI  - What it really takes to become a nurse.

PMID- 8568697
TI  - The rewards of the sandwich generation.

PMID- 8568698
TI  - Luck of the draw. Skills testing for retention.

PMID- 8568699
TI  - 'Tis the season for flu prevention.

PMID- 8568700
TI  - New first aid survey reveals good intentions, bad habits.

PMID- 8568701
TI  - Americans spend one-third of their days in pain.

PMID- 8568702
TI  - Pulling the plug!

PMID- 8568703
TI  - Can practical nursing survive? A look at its proud history, and its promising
      future.

PMID- 8568704
TI  - My rose garden; a close-up view of the mentally ill shows they're like flowers
      planted in an alley.

PMID- 8568705
TI  - Therapeutic drug monitoring.

PMID- 8568706
TI  - Dyslipoproteinemia in renal transplantation.
AB  - Twenty-seven live related donor renal allograft recipients were evaluated for
      dyslipoproteinemia. Twenty-two patients received dual immunosuppression with
      prednisolone and azathioprine. Five patients received cyclosporin as well. Total
      cholesterol (Tch), triglycerides (TG), HDL cholesterol (HDLch), LDL cholesterol
      (LDLch) and VLDL cholesterol (VLDLch) levels were estimated. Fifteen (56%)
      patients showed significant lipoprotein abnormalities. Renal allograft recipients
      showed significantly lower levels of Tch (p < 0.05) and LDLch (p < 0.05) and
      higher levels of TG (p < 0.005) and HDLch (p < 0.05). Diet and beta blockers did
      not influence lipoprotein levels. A significant negative correlation was noted
      between post-transplant duration and Tch, TG and VLDLch levels. Increased TG
      levels were associated with increase in weight and higher daily prednisolone
      dosage at the time of evaluation. The study confirms the existence of
      dyslipoproteinemia in renal allograft recipients.

PMID- 8568707
TI  - The rationale of argon green laser photocoagulation for diabetic maculopathy.
AB  - Eighty-four patients of bilateral diabetic retinopathy were divided into 2
      groups: Group I comprised of 60 patients (mean age 46 yrs) having non
      proliferative diabetic retinopathy with maculopathy (total no. of eyes = 120).
      Group II consisted of 24 patients (mean age 49.1 yrs) with proliferative diabetic
      retinopathy with maculopathy (total no. of eyes under study = 48). One eye of
      each patient in group I was treated as a control and the other was subjected to
      focal laser therapy. While 48/60 control Group I eyes (80%) had 6/24 vision at
      the outset, at one year follow-up only 39/60 cases (65%) had 6/24 vision.
      Diabetic maculopathy persisted in all the 60 control eyes at one year. In
      contrast, 44/60 eyes (73%) subjected to focal laser therapy in Group I, had 6/24
      vision at outset but one year later, 49/60 eyes (81%) had 6/24 vision.
      Maculopathy completely regressed in 48/60 eyes (80%). The 48 eyes of Group II
      patients were subjected to focal and scatter laser therapy. 20/48 eyes (41.6%)
      had 6/24 vision prior to treatment but one year after treatment, 25/48 eyes (52%)
      had 6/24 vision. Neovascularization and macular edema regressed after one year in
      42/48 eyes (87.1%) and only 4/48 eyes (8.3%) developed localized vitreous
      hemorrhage. Laser therapy in Group I improved visual acuity by reducing macular
      edema. In Group II, it improved the vision and reduced the risk of vitreous
      hemorrhage, detachment and glaucoma.

PMID- 8568708
TI  - Bacteriological profile of neonatal septicemia cases (for the year 1990-91).
AB  - Blood culture reports were studied in 1266 cases of clinically suspected neonatal
      septicemia, to determine the bacteriological profile and antibiotic sensitivity
      pattern of the cultured isolates. Blood culture was positive in 24.88% of cases.
      Gram negative septicemia was encountered in 87.1% of these neonates. Klebsiella
      and Enterobacter species were the predominant pathogens amongst Gram negative
      organisms. Of Gram positive isolates, Staphylococcus aureus was the predominant
      isolate (79.0%). Salmonella species was isolated in 2.4% of these cases.

PMID- 8568710
TI  - Post-natal somatic cell gene therapy.

PMID- 8568709
TI  - Haemorheology in diabetic foot.
AB  - A prospective study was undertaken to study the haemorheology in patients with
      diabetic foot lesions. Haemorheology of 30 patients with foot lesions and 30 age
      and sex matched controls was studied. The haemorheological parameters evaluated
      were whole blood and plasma viscosity and RBC filter ability. Plasma viscosity
      was significantly increased (p < 0.05). It substantiates the need for using
      rheomodulators in management of diabetic foot lesions.

PMID- 8568711
TI  - Anaesthesia and craniofacial surgery.

PMID- 8568713
TI  - Isthmico-cervical ectopic pregnancy following caesarean section.
AB  - A 30 year old woman (gravida 4, para 2) presented with 2 1/2 mth amenorrhoea and
      vaginal spotting. On bimanual pelvic examination, an old tear was felt on
      posterior cervical lip with enlarged cervix and normal sized uterus.
      Ultrasonography revealed ectopic pregnancy with placenta implanted on isthmus and
      upper cervix. Dilatation and curettage was done with cervical packing.

PMID- 8568712
TI  - Malignant melanoma of nasopharynx extending to the nose with metastasis in the
      neck.
AB  - Malignant melanoma is a rare tumor in otorhinolaryngology. In this paper, we have
      reported the first case of melanoma of nasopharynx which we came across in 20
      years of ENT practice. A 55 year old male patient with complaints of swelling of
      nose and left side of neck, nasal blockage and epistaxis was diagnosed as
      melanoma of nose with metastasis in the neck based on clinical and radiological
      examination. The tumour was excised by lateral rhinotomy with supraomohyoid block
      dissection on the left side. The tumour was found to originate from lateral wall
      of nasopharynx and middle turbinate. The surgery was followed by radiotherapy.
      Diagnosis of melanoma was confirmed on histopathology. During 30 months follow
      up, no recurrence was noticed.

PMID- 8568715
TI  - Brown tumor of the hard palate in secondary hyperparathyroidism.
AB  - Jaw bones are rarely involved in secondary hyperparathyroidism. We report a case
      of 13 year old girl who presented with progressive chronic renal failure and
      secondary hyperparathyroidism. Five months after beginning of hemodialysis, a
      large brown tumor developed on the hard palate, extending to the maxilla causing
      difficulty in swallowing and breathing. She died of massive intestinal hemorrhage
      five months after excision of the mass.

PMID- 8568714
TI  - Rapid enlargement of subdural haematoma.
AB  - A case of subdural haematoma (SDH) having atypical features (headache, vomiting,
      drowsiness but normal haematological and metabolic parameters and no localising
      neurological signs) is reported. The SDH rapidly enlarged and liquefied in five
      days as evident on computerised tomographic (CT) scan and operative findings.
      Rapid improvement was observed following this. Abnormally excessive fibrinolytic
      activity in the SDH is a possible cause.

PMID- 8568716
TI  - Acute appendicitis mistaken as acute rejection in renal transplant recipients.
AB  - Case histories of 2 renal transplant recipients are reported who had presenting
      features of fever, leukocytosis and pain/tenderness over right iliac fossa and
      were diagnosed to be due to acute appendicitis rather than more commonly
      suspected acute rejection episode which has very similar features. Diagnosis of
      acute appendicitis was suspected on the basis of rectal examination and later
      confirmed by laparotomy. The purpose of this communication is to emphasize the
      need for proper diagnosis in patient with such presentation; otherwise wrong
      treatment may be received.

PMID- 8568718
TI  - The mythology of modern medicine--IV. HIV: heuristically important virus. AIDS:
      advances induced deficiency syndromes.

PMID- 8568717
TI  - 9p-Syndrome.
AB  - A 2 1/2 month old male child was admitted with loose motions and mild
      dehydration. He was full term normal delivery, born of a non-consanguinous
      marriage. On examination, he had trigonocephaly; anteverted nostrils, long
      philtrum and hypoplastic supraorbital ridges. X-ray showed sutural separation.
      Karyotyping confirmed deletion of short arm of chromosome 9 distal to band p22.

PMID- 8568719
TI  - Statistics in medical research--IV. Sampling distribution, statistical testing of
      hypothesis and student's t-test.

PMID- 8568720
TI  - Determination of pyrazinamide in human by high performance liquid chromatography.
AB  - A facile and sensitive high performance liquid chromatographic (HPLC) technique
      has been developed for the determination pyrazinamide (PZA) in human plasma.
      Nicotinamide(NIA) is used as internal standard(IS). Plasma is deproteinized with
      0.7 M perchloric acid; clear supernatant is neutralized with 1M NaOH and injected
      onto HPLC. The separation of pyrazinamide and the internal standard is carried
      out on a Supelco LC-18 (DB) column with a basic mobile phase. Pyrazinoic acid,
      the major metabolite, other anti-tuberculous drugs and endogenous components do
      not interfere with measurement of pyrazinamide. The limit of detection of
      pyrazinamide with this method is 0.2 mg/0.2 ml plasma (CV 8.2%).

PMID- 8568721
TI  - Spontaneous alternation, motor activity, and spatial learning in hot-foot mutant
      mice.
AB  - Hot-foot mutant mice, characterized by defective innervation of Purkinje cells
      and an ataxic gait, were less active than normal mice in a T-maze. In spontaneous
      alternation testing with either single or multiple trials, hot-foot mutants,
      contrary to normal mice, did not alternate above chance. Moreover, the mutants
      had a higher number of errors and higher escape latencies in a water-filled Z
      maze. These results indicate that in addition to motor coordination deficits,
      these cerebellar mutants have deficits in spatial learning and perseverate
      choices of maze arms.

PMID- 8568722
TI  - Serotonin-induced changes in the excitability of cultured antennal-lobe neurons
      of the sphinx moth Manduca sexta.
AB  - The modulatory actions of 5-hydroxy-tryptamine (5HT or serotonin) on a
      morphologically identifiable class of neurons dissociated from antennal lobes of
      Manduca sexta at stages 9-15 of the 18 stages of metamorphic adult development
      were examined in vitro with whole-cell patch-clamp recording techniques. Action
      potentials could be elicited from approximately 20% of the cells. These cells
      were used to examine effects of 5HT (5 x 10(-6) to 5 x 10(-4) M) on cell
      excitability and action-potential waveform. 5HT increased the number of spikes
      elicited by a constant depolarizing current pulse and reduced the latency of
      responses. 5HT also led to broadening of action potentials in these neurons and
      increased cell input resistance. Modulation of potassium channels by 5HT is
      likely to contribute to these responses. 5HT causes reversible reduction of at
      least 3 distinct potassium currents, one of which is described for the first time
      in this study. Because effects of 5HT on antennal-lobe neurons in culture mimic
      those observed in situ in the brain of the adult moth, in vitro analysis should
      contribute to elucidation of the cellular mechanisms that underlie the modulatory
      effects of 5HT on central olfactory neurons in the moth.

PMID- 8568723
TI  - Neurotransmitters regulate rhythmic size changes amongst cells in the fly's optic
      lobe.
AB  - Axon calibre in monopolar cells L1 and L2 of the fly's lamina can change
      dynamically. Swelling by day, L2 exhibits a daily rhythm of changing size
      apparently mediated by wide-field LBO5HT and PDH cells. L1/L2 axon profiles were
      measured planimetrically in the housefly, Musca domestica, from 1 microns cross
      sections. Four hours after injecting 80-100 nl of 1.25 x 10(-4) M 5-HT into the
      optic lobe, L1's axon swelled but L2's did not, whereas 2.2 x 10(-5) M of PDH
      enlarged both axons. Similar to 5-HT, 1.63 x 10(-4) M histamine (the
      photoreceptor transmitter) enlarged L1 but not L2, mimicking light exposure,
      while 1.7 x 10(-4) M glutamate and 1.94 x 10(-4) M GABA both decreased L1 and L2.
      2.5 x 10(-4) M of 5,7-dihydroxytryptamine decreased L2 and, somewhat, L1, an
      effect attributable to the loss of LBO5HT neurites. Twenty four hours after
      cutting LBO5HT and PDH commissural pathways, L1 and L2 both shrank. Apparently,
      L2's size depends on either LBO5HT or sufficient 5-HT, and L1 and L2 have
      different response ranges to 5-HT. Responses to PDH imply that daytime PDH
      release drives a circadian rhythm, enlarging L1 and L2.

PMID- 8568724
TI  - Olfactory control of behavior in moths: central processing of odor information
      and the functional significance of olfactory glomeruli.

PMID- 8568725
TI  - Liability for psychiatric illness.

PMID- 8568726
TI  - Medicine and the law: conflict or debate.

PMID- 8568727
TI  - The post-concussional syndrome: physiogenesis, psychogenesis and malingering. An
      integrative model.
AB  - Current models of post-concussional symptoms after mild head injury rest on the
      dichotomy between organic and psychogenic factors, which underpins Lishman's
      formulation; organic genesis and psychologically-driven persistence (Br J
      Psychiatry 1988; 153: 460-469). Recent prospective neuropsychological and bio
      social studies of mild head injury, and perspectives from cognitive behavioural
      and health psychology, are reviewed. It is argued that the organic-psychogenic
      conceptualization inadequately explains chronic post-concussional symptoms.
      Psychosocial and cognitive-behavioural factors and the coping process may
      influence post-concussional symptoms over their entire time course, in particular
      the late phase. A multifactorial model of chronic post-concussional symptoms is
      proposed which integrates biological processes with these factors. It is through
      the recognition and identification of separate processes that questions about
      outcome, the limits of the impact of organic and psychosocial factors, the nature
      of exaggeration, and appropriate therapy, may be resolved.

PMID- 8568728
TI  - 'Compensation neurosis' revisited: outcome studies of the effects of litigation.
AB  - Although the term 'compensation neurosis' has been frequently used to describe
      personal injury litigants, its clinical validity--and the assumptions about
      individuals described by this label--have not been critically examined. This
      article reviews the concept of 'compensation neurosis' and follow-up studies of
      claimants for compensation following the finalisation of their legal proceedings.
      A follow-up study of 760 litigants found that, of the 264 subjects who were not
      working at the time of conclusion of litigation and who could be traced, 198
      (75%) were not working after an average of 23 months following the finalization
      of their cases.

PMID- 8568729
TI  - Occupational stress and the law: some current issues for employers.

PMID- 8568730
TI  - Legal and medical aspects of liability for negligently occasioned nervous shock:
      a current perspective.
AB  - This article examines recent developments in Australian and English common law
      relating to negligently occasioned psychiatric illness (nervous shock) in the
      light of advances in understanding of aetiology, neurophysiology and psychology
      of emotional injury. The legal analysis focuses on the modern concept of
      proximity relationship between the plaintiff and the defendant. The courts use
      the notion of proximity to determine the existence of duty of care in cases
      involving liability of the defendant for the negligent infliction of 'mere'
      nervous shock; that is where the plaintiff who had not been present at the site
      of the accident in which a close relative or a co-worker has been negligently
      killed or injured, claims to have suffered a lasting psychoneurosis or a
      psychosomatic illness as a result of a sudden and severe emotional distress
      occasioned by the defendant's wrongful act. Cases from the US, [1] Canada, [2]
      South Africa [3] and New Zealand [4] are not discussed; to include them would
      have involved too much exposition in comparison to their influence upon the
      development of the law of nervous shock. Nevertheless, since the developments
      described below concern the core question of law, the nature and the ambit of
      defendant's liability for unintentionally occasioned psychiatric damage, they
      will have to be considered in any jurisdiction in which this question arises.

PMID- 8568731
TI  - 'Functional overlay', and illness behaviour in chronic pain: distress or
      malingering? Conceptual difficulties in medico-legal assessment of personal
      injury claims.

PMID- 8568732
TI  - Problems in the assessment of psychosomatic conditions in Social Security
      benefits and related commercial schemes.
AB  - The medical community must recognize that support of claims for Incapacity
      Benefit and related commercial schemes places the patient in a small and special
      sub-population of clinical practice which may require specialist investigation,
      treatment, and documentation. Determination of functional capacity and of
      disability requires knowledge either not available or unfamiliar to most
      physicians with caring and therapeutic roles, especially of legal or contractual
      provisions and occupational data. However, it is not necessary for them to
      determine disability and they should not be asked to do so. The new, medical
      assessment procedures for Incapacity Benefit in the UK do not require this, and
      the largest provider of related commercial schemes (Long Term Disability;
      Permanent Health Insurance) has already eliminated this requirement from its
      application process. When such application is anticipated or requested, the
      medical record should be prepared and appropriate consultation obtained.
      Subjective issues should be identified and addressed. Comprehensive psychiatric
      evaluation, especially in subjective impairment, is critical in chronic
      incapacity. The estimation of functional capacities in the absence of objective
      data is particularly troublesome, but, clinicians can provide the Disability
      Medical Analyst with appropriate medical documentation.

PMID- 8568733
TI  - The detection of exaggerated or simulated memory disorder by neuropsychological
      methods.
AB  - Some neuropsychological tests devised to detect exaggeration and simulation of
      memory disorder are reviewed with reference to models of memory and our current
      knowledge of the behaviour of amnesic patients. These tests are based on the
      assumption that naive simulators or exaggerators do not know either that amnesic
      patients can perform them normally, or near normally, or that subjects can only
      fail them by deliberate suppression of the correct response. It is concluded that
      several such tests show promise and are worthy of further development.

PMID- 8568734
TI  - What is the evidence for an organic lesion in whiplash injury?

PMID- 8568735
TI  - 'Repetitive strain injury': from Australia to the UK.
AB  - The UK is now experiencing an epidemic of upper limb pain similar to that which
      affected Australia in the 1980s. The pain is often non-specific, and does not
      conform to the pattern of various well-recognized rheumatological entities. The
      syndrome is known by a number of terms, some of which imply an aetiological link
      to workplace activities unsubstantiated by hard evidence. The syndrome may well
      be largely psychosocial, and analogous to the chronic fatigue syndrome. It is
      currently the cause of many contentious and well-publicized medico-legal cases.
      Possible factors behind the epidemic will be discussed, and an approach to
      management suggested.

PMID- 8568736
TI  - Medico-legal aspects of road traffic accidents.

PMID- 8568737
TI  - Functioning free muscle transplantation to the lower leg.
AB  - Many authors have reported on transplantation of functioning free muscle to the
      upper extremities, but few reports are available on functioning free muscle
      transfers to the lower extremities, where injuries have hitherto been treated
      mainly with tendon transfers. However, under suitable conditions, better results
      can be obtained using a functioning free musculocutaneous flap transfer to treat
      extensor muscle loss in the lower leg. The authors reconstructed the anterior
      extensors in two patients suffering from lower-leg necrosis. Ankle-joint active
      dorsiflexion was restored, and dorsiflexion in the ankle joint of about 0 degree
      was achieved; however, recovery of ankle-joint range of motion was limited by
      contracture of the ankle joint, due to associated injury, even when the strength
      and excursion of the grafted muscle were sufficient.

PMID- 8568738
TI  - Is surface cooling effective for tissue preservation in free-flap surgery?
AB  - Effective tissue cooling can extend the period of safe ischemia. To determine
      whether the technique of surface cooling could produce an effectively low core
      temperature (4 degrees to 10 degrees C) in the flap core in a reasonable amount
      of time, bovine muscle/subcutaneous fat flaps, weighing 400, 800, and 2000 g,
      were brought to 37 degrees C and then surface cooled. Temperatures were then
      recorded every 5 min. All flaps were able to attain 4 degrees C in the core; the
      average times for the 400, 800, and 2000 g flaps to reach 4 degrees C were 136,
      153, and 194 min, respectively. Although a clear inverse relationship existed
      between flap weight and effectiveness of core cooling, even relatively large
      flaps (2000 g) could still achieve sufficiently low core temperatures from
      surface cooling well within tolerable warm ischemia time. Concern for ischemia
      time generally should not interfere with efficient, orderly, free-flap surgery.

PMID- 8568739
TI  - Two-dimensional analysis of hemodynamic changes in axial and random pattern
      flaps.
AB  - The present study was performed to evaluate the time course of hemodynamic change
      in axial and random pattern flaps two-dimensionally. The axial pattern flap,
      including the central auricular artery and vein, and the random pattern flap
      without these vessels were created in the auricles of the rabbit. The blood flow
      of these flaps was investigated and assessed using laserflowgraphy, which
      provides a two-dimensional analysis of microcirculation. In the axial pattern
      flap, a gradient of blood flow toward the short axis of the flap and decreased
      blood flow in the surrounding area were noticed immediately after operation. The
      hemodynamic changes became less marked with time. In the random pattern flap, a
      gradient of blood flow toward the long axis of the flap was noticed around 6 hr
      after operation and the blood flow in the surrounding area increased throughout
      the investigations.

PMID- 8568740
TI  - Evaluation of a continuous systemic infusion of iloprost, a stable PGI-2 analog,
      on the survival of experimental skin flaps.
AB  - Numerous investigators have attempted to enhance the survival of ischemic
      experimental skin flaps using various pharmacologic manipulations. Recently, the
      authors' laboratory demonstrated the beneficial effect of iloprost, a stable PGI2
      analogue, as a post-ischemic perfusion washout, in improving the survival of
      ischemic skin flaps. The rat unilateral abdominal skin flap, based on the
      superficial epigastric vessels, was utilized in this study involving 30 animals.
      The animals were divided into three different treatment groups, with ischemic
      periods of 16 and 18 hr. Perfusion washouts were performed at the completion of
      the various ischemic periods. Alzet osmotic pumps were used to deliver a
      continuous systemic infusion of iloprost for 7 days postoperatively. The groups
      consisted of the following: Group 1 (single ILO)--perfusion washout with iloprost
      only; Group 2 (continuous LD ILO)--low-dose systemic iloprost infusion (0.066
      mcg/kg/min) and perfusion washout with iloprost; and Group 3 (continuous HD ILO)-
      high-dose systemic iloprost infusion (0.1 mcg/kg/min) and perfusion washout with
      iloprost. The percentage of flap survival was assessed on postoperative day 7.
      Skin flaps of the animals receiving the continuous systemic infusion of iloprost
      were noted to have varying percentages of survival, while skin flaps undergoing
      perfusion washout only were found to have either complete survival using a
      continuous systemic infusion of iloprost, compared to iloprost perfusion washout
      alone. In addition, the hypotensive side effects of systemic iloprost infusion
      limit its use in the rat skin-flap model.

PMID- 8568741
TI  - Vascular variation of the radial forearm flap: a case report.
AB  - Anomalies of the radial forearm flap have been reported; however, rarely does one
      encounter variations that jeopardize the vascular supply of the flap. In the
      reported case, an anomalous superficial vessel in the forearm supplied the skin
      island of the radial forearm flap. In addition, there were no perforating vessels
      from the radial artery.

PMID- 8568742
TI  - Endoscopic retrieval of the sural nerve.
AB  - The rapid proliferation and applications of endoscopic-guided systems have
      transcended all surgical specialties. The future as regards reconstructive
      microneurosurgery is uncertain but inevitable, as already characterized by
      efforts to seek an alternative method for harvest of the sural nerve. Although
      still a primitive technique, endoscopic assistance in the retrieval of long,
      sural-nerve grafts has been found to minimize the trauma and morbidity of
      dissection; can simplify identification of frequently anomalous branches; and
      allows a reduction of the number of incisions, to improve the aesthetic result.

PMID- 8568743
TI  - Free flap with reversed arterial flow in the leg: case report.
AB  - A case of distal-third reconstruction of a leg with bone exposure is reported. A
      rectus abdominis muscle free flap, based on the inferior epigastric artery, was
      anastomosed to the distal stump of the anterior tibial artery with reversed flow.
      This technique is suggested as an option for microvascular reconstruction in the
      distal third of the leg. Anatomic and physiologic details are discussed.

PMID- 8568744
TI  - Motor evoked potential as a reliable method to verify the conductivity of
      anterior spinal roots in brachial plexus surgery: an experimental study on goats.
AB  - The goal of this experimental study was to confirm the reliability of motor
      evoked potential (MEP) in testing the function of anterior motor roots in
      brachial plexus surgery. On central stimulation, nerve compound action potentials
      (NCAPs) are registered from the exposed spinal nerves. If NCAPs can be recorded,
      the anterior root is considered to be intact. Two factors might cause positive
      recordings even in the presence of an avulsed anterior motor root: volume
      conduction, and impulse transmission through an intact posterior root. In five
      Nubian goats, spinal nerves C6, C7, and their corresponding spinal roots were
      dissected. On central stimulation, NCAPs were repeatedly recorded from the
      surface of all ten spinal nerves. Then, the anterior motor roots were transsected
      and central stimulation repeated. NCAPs disappeared irreversibly in all ten
      tested spinal nerves. The experiment showed that, on central stimulation, NCAPs
      cannot be recorded from spinal nerves unless the anterior root is intact.

PMID- 8568745
TI  - In search of health--the RAMC contribution to APRE.

PMID- 8568746
TI  - Potential recruits referred for cardiac opinion review of 100 consecutive cases-
      a waste of time or an investment?
AB  - Eighty seven of 100 consecutive recruits referred for cardiac assessment of
      fitness to serve had heart murmurs. Seven of these were rejected as having
      significant cardiac disease. One with a diagnosis of hypertrophic cardiomyopathy
      would have been placed at considerable risk had he been exposed to the physical
      stress of military training. The remaining 6 rejected had conditions which could
      have been worsened by the stress of military training and/or required intensive
      cardiac follow-up. These included 3 individuals with aortic regurgitation, 1 with
      atrial septal defect, 1 with ventricular septal defect combined with a small
      atrial septal defect and 1 with post rheumatic fever mitral regurgitation.
      Thirteen patients we assessed because of other cardiac problems including
      repaired congenital heart disease and hypertension. The rejection rate in this
      group was high at 10 out of 13. The majority of those referred (83/100) were
      found to be fit for military service. Five of these required advice on antibiotic
      prophylaxis but the majority had totally unrestricted service. Although most
      recruits who present with cardiac "problems" will be fit for service, important
      and potentially fatal conditions can be detected. Therefore vigilance must be
      high amongst examining doctors and suspect individuals referred for appropriate
      assessment.

PMID- 8568747
TI  - The employability of pregnant and breastfeeding servicewomen.
AB  - The Army Medical Services are responsible for promoting health in the military
      workplace. A survey of the potential health risks in the workplace to British
      Army servicewomen who are pregnant, or who breastfeed, was carried out. It was
      found that there was a total of 30 major workplace hazards to pregnant or
      breastfeeding servicewomen, and that medical guidance in this area was lacking. A
      Medline literature search on these hazards, was compiled, and an overview of the
      nature and extent of the military problem, together with a brief policy
      recommendation applying to each hazard. Guidelines based on these recommendations
      were distributed to primary care and obstetric unit medical officers in all three
      Armed Services. It is intended that the guidelines will assist Service doctors in
      giving informed advice on the avoidance of military occupational risks to
      pregnancy and to lactation.

PMID- 8568748
TI  - Options for screening for colorectal cancer in the Royal Air Force: a cost
      effectiveness evaluation.
AB  - Colorectal cancer (CRC) is the second most common form of malignancy, causing
      death after late presentation in two-thirds of cases. Early detection makes
      curative treatment likely. Faecal occult blood tests (FOBTs) detect some pre
      symptomatic CRCs and their precursor lesions, adenomatous polyps. A trial showed
      reduced mortality in USA volunteers aged 50-80 with regular FOBTs; both this and
      the Nottingham population-based trial detected earlier-stage CRCs. Current US
      guidelines recommend annual digital rectal examination and FOBTs from age 40.
      FOBTs have been included in the USAF examination of aircrew for several years.
      Day-case colonoscopy, with appropriate biopsy-excision, is the first-choice
      follow-up investigation. This study aims to investigate the design of any
      programme to introduce FOBTs as part of the RAF's existing schedule of Periodic
      Medical Examinations (PMEs) and Screenings, and the age groups to be included,
      rather than the decision as to whether or not it should be commenced. The
      analysis therefore examines the cost per cancer detected. The information
      required to evaluate subsequent outcomes, such as cost per life-year saved, is
      not available for the RAF population so speculative extrapolation from other data
      is not attempted. Over a third of RAF personnel are under the age of 25, nearly
      three-quarters under 35 and over four-fifths under 40. Over a quarter of the 4
      RAF CRC cases pa occur under age 40 and two-thirds under 50. The most cost
      effective age at which to introduce FOBTs in the RAF is 40, regardless of the
      following parameters. Assuming FOBT sensitivity of 55% and positivity 5%, FOBT
      costing 23p and colonoscopy 175 pounds, starting FOBTs RAF-wide at age 40 would
      cost annually 35,968 pounds and 15,881 pounds per CRC case detected. The FOBT
      contribution to the costs is extremely small and the importance of maximising
      sensitivity and specificity very great. Hence dietary modification, and using a
      test or combination of tests with higher sensitivity and/or lower false
      positivity, even if much more expensive, would be highly cost-effective, reducing
      the above costs substantially. Counting as "cases" persons with adenomas reduces
      the cost per "case" detected by about 75%. A pilot study is proposed concerning
      the introduction on selected stations of FOBTs with RAF PMEs/Screenings, from age
      40, to determine: sensitivity and false-positivity rates for single and serial
      FOBTs, and the predictive value of positive tests, in RAF screenees; the annual
      cost; the costs per CRC case, and per CRC-plus-adenoma case, detected; possibly,
      an estimate of the cost per life-year saved; and, hence, whether the programme
      should be extended to all RAF personnel. FOB screening from age 40 would miss the
      quarter of RAF CRC cases which occur in personnel under 40. Identification is
      therefore recommended now of personnel at high risk for CRC, because of personal
      or family history, at all PMEs/Screenings, regardless of age, with the subsequent
      offer of serial FOBTs annually and regular colonoscopy. 2 1/2 yearly [corrected]
      FOBTs, done with PMEs/Screenings and half-way through the 5 year interval, would
      detect almost as many CRCs as annual testing, missing only half as many as 5
      yearly testing. This analysis provides information on the costs and consequences
      of various FOB screening strategies for the RAF and other Services. Similar
      principles can be applied to develop informed strategies for other screening.

PMID- 8568749
TI  - Why do insects bite? A review of blood sucking behaviour.

PMID- 8568750
TI  - Heat illness--a review of military experience (Part 1).
AB  - This paper is the first part of a two part review of the published literature
      reporting the military experience of heat illness. It summarises current concepts
      of the mechanisms for the development of heat illness. The reports of heat
      illness in the military medical literature from pre-World War 1 to the end of
      World War 2 are discussed. The second part will consider reports from the end of
      the Second World War to the present day. Epidemiological evidence for the factors
      causing heat illness will be summarised and finally the current areas of
      uncertainty will be identified with proposals for future research.

PMID- 8568751
TI  - Rhabdomyosarcoma arising in teratoma of the testis.
AB  - Rhabdomyosarcoma arising in teratoma of the testis is an exceptionally rare
      occurrence. The rhabdomyosarcomatous element infers a less favourable prognosis
      and standard treatment regimes well recognised for the treatment of teratoma of
      the testis may not be effective.

PMID- 8568752
TI  - Atrio-ventricular dissociation in meningococcal meningitis.
AB  - A case is presented of meningococcal meningitis, without septicaemia, which was
      associated with a transient atrio-ventricular dissociation. The need for cardiac
      monitoring in similar cases is discussed.

PMID- 8568753
TI  - Methicillin resistant Staphylococcus aureus in a liver abscess.

PMID- 8568754
TI  - Foreign bodies of dental origin in the appendix.
AB  - Foreign bodies found in the appendix have been reported many times. To date 254
      occurrences have been documented. However, only 4 previously reported episodes
      involve teeth, dental restoration or dental equipment. We present a patient with
      a 6 month history of intermittent right iliac fossa pain following the ingestion
      of a gold inlay restoration, which was found at operation to be in the distal
      appendix. Previous reports suggest that symptoms from foreign bodies in the
      appendix occur in 73% of cases, and in 93% when the object is sharp. Therefore,
      appendicectomy is recommended when a foreign body is detected in the appendix,
      and particularly if it has sharp edges.

PMID- 8568755
TI  - Reconstruction of laryngotracheal war injuries with the median layer of the deep
      cervical fascia.

PMID- 8568756
TI  - Heat illness and cystic fibrosis.

PMID- 8568757
TI  - Exercise ECG's.

PMID- 8568758
TI  - Methodology and characterization of an in vitro perfusion model for the mouse
      ovary.
AB  - Perfusion of intact ovaries in vitro has proved to be a suitable model for the
      study of ovarian events, such as ovulation and corpus luteum function, with
      advantages over cell culture systems of preserved three-dimensional structure
      with intact intercellular communication. This methodology has been described for
      several larger experimental animals. Development of genetically manipulated mouse
      strains and the larger availability of recombinant proteins and monoclonal
      antibodies in this species prompted the development of a mouse ovary perfusion
      system. In the present study, we describe the methodology for perfusion of mouse
      ovaries in vitro and characterize the model with respect to steroidogenesis,
      ovulatory efficiency and morphology. Swiss mice (30-45 g) were synchronized with
      a single injection of a GnRH agonist and laparotomy was performed on the morning
      of pro-oestrus. The right ovary and its vasculature, after cannulation on the
      arterial side, were surgically isolated and transferred to a recirculating
      perfusion system, and were perfused for 20 h. The ultrastructure of the ovaries
      after 20 h of perfusion was examined by transmission electron microscopy, which
      showed well-preserved cellular organelles and nuclei and distinct tight junctions
      between endothelial cells. Unstimulated ovaries did not ovulate and secreted
      small quantities of progesterone. After addition of hCG (50 iu) or ovine LH (0.1
      microgram ml-1), ovulations were observed in all perfused ovaries (2.6 +/- 0.5
      and 2.0 +/- 0.3 ovulations per treated ovary, respectively). There was a distinct
      rise in progesterone output after hormone addition. When a phosphodiesterase
      inhibitor, isobutylmethylxanthine (0.2 mumol l-1), was added in combination with
      LH, the ovulation rate (7.4 +/- 1.2) was similar to that in vivo and progesterone
      secretion was further increased compared with other treatments. Since the mouse
      has become a very important experimental animal in medical research and we have
      the ability to genetically manipulate this species, this methodology for
      perfusing mouse ovaries in vitro may be a useful tool in future studies of
      ovarian physiology.

PMID- 8568759
TI  - Influence of sperm movement parameters on human sperm-oolemma fusion.
AB  - Flagellar dyskinesia is characterized by abnormal sperm movement parameters and a
      negative sperm mucus penetration test. It is associated with structural
      pathologies of the axonemal complex (lack of outer dynein arms), of the
      periaxonemal complex (sliding spermatozoa and periaxonemal dyskinesia), or of
      both structures (short flagella). Even during in vitro fertilization, dyskinesia
      prevents the spermatozoon from getting through the egg vestment. However, in some
      cases, fertilization has been achieved using subzonal insemination. Flagellar
      dyskinesia is therefore an interesting model for investigating the role of sperm
      movement in the fusion process between the spermatozoon and the oolemma. Thirty
      one patients requiring assisted fertilization were included in the study. Fifteen
      had spermatozoa in which the flagellum lacked outer dynein arms, 11 had anomalies
      of the periaxonemal complex (five with sliding spermatozoa and six with
      periaxonemal dyskinesia) and five had spermatozoa with short flagella. Seven men
      who produced spermatozoa with normal movement were selected as controls. Movement
      was evaluated using a computer-assisted analyser, and penetration was assessed
      using zona-free hamster eggs. At 37 degrees C, in semen, the dyskinetic
      spermatozoa had reduced straight line and curvilinear velocity and lateral head
      displacement compared with controls (P < 0.01). In the Percoll-selected sperm
      suspension, the only difference was that spermatozoa with periaxonemal anomalies
      maintained a narrow lateral head displacement compared with the controls (P <
      0.001). After 3 h of incubation at 37 degrees C, the lateral head displacement of
      dyskinetic spermatozoa had not changed, while that of the controls showed a
      significant increase (4.5 to 5.6 microns; P < 0.05). The results from the sperm
      penetration assay for the spermatozoa lacking outer dynein arms were lower than
      those of the controls (47% versus 77%; P < 0.05) and the results for sliding
      spermatozoa and spermatozoa with periaxonemal dyskinesia were even lower (25% and
      34%, respectively; P < 0.01). The fertilization rates after subzonal insemination
      were 46.5% for spermatozoa lacking outer dynein arms, 36.1% for spermatozoa with
      short flagella, 24.8% for sliding spermatozoa and 17.3% for spermatozoa with
      periaxonemal dyskinesia. There was a significant correlation between the
      curvilinear velocity of the Percoll-selected sperm suspensions and their
      fertilization rates after subzonal insemination (r = 0.5; P < 0.05) and their
      sperm penetration assays (r = 0.7; P < 0.001). The data provide evidence that
      sperm velocity is correlated with the ability to fuse with the oolemma.

PMID- 8568760
TI  - Premating and gestational effects of maternal nutrition on secondary sex ratio in
      house mice.
AB  - Pregnant female house mice maintained on a consistent low-food diet give birth to
      a lower proportion of males than do control females fed ad libitum. Because house
      mice may experience daily fluctuations in food availability, we tested whether
      intermittent feeding during gestation influences the sex ratio of the offspring.
      In addition, we tested whether intermittent feeding has asymmetrical effects on
      the masses of adult male and female offspring. Females deprived of food every
      other day one week before mating and those deprived every third day during
      gestation produced a lower proportion of males than did control (fed ad libitum)
      females. Males born to females that were deprived of food during gestation had
      the same body mass at birth as males born to control females, but as adults their
      mass was lower than that of control males. There were no differences in the birth
      or adult body masses of female offspring. Because males of low body mass may have
      relatively low lifetime reproduction, our results support the Trivers-Willard
      model of sex ratio variation.

PMID- 8568761
TI  - Ingestion of n-3 polyunsaturated fatty acids and ovulation in rats.
AB  - The effects of different ratios of dietary (n-3):(n-6) polyunsaturated fatty
      acids on prostaglandin E, prostaglandin F2 alpha and ovulation in rats were
      assessed. Dietary (n-3) polyunsaturated fatty acids were incorporated, by ovarian
      phospholipids with ovarian tissue enrichment, with (n-3) polyunsaturated fatty
      acids enhancing, and (n-6) polyunsaturated fatty acids reducing, the number of
      ova released in immature rats primed with pregnant mares' serum gonadotrophin and
      human chorionic gonadotrophin. Incorporation of (n-3) polyunsaturated fatty acids
      appeared to enhance ovulation by altering total prostaglandin E production. This
      effect may be induced by changes in the prostaglandin E3:E2 ratio and the
      synthesis of less biologically active prostaglandin E3, or by dilution of the
      anti-ovulatory properties attributable to prostaglandin E2. High incorporation of
      dietary (n-6) polyunsaturated fatty acids may lead to reduced ovulation through
      excessive production of prostaglandin E2. Prostaglandin E or F2 alpha and
      alterations in tissue phospholipid composition inhibited progesterone release,
      and inhibition was independent of the series of prostaglandin produced. This
      study provides evidence that dietary lipids affect ovulation in rats with
      possible implications for reproduction in other vertebrates.

PMID- 8568762
TI  - Localization of vascular endothelial growth factor and its receptor, flt, in
      human placenta and decidua by immunohistochemistry.
AB  - Vascular endothelial growth factor is a secreted angiogenic growth factor the
      mRNA of which is present in the placenta. The mRNA encoding the vascular
      endothelial growth factor receptor, flt, has also been demonstrated in placenta,
      with trophoblast appearing to be a novel site of flt expression. We investigated
      the expression of both vascular endothelial growth factor and flt-like
      immunoreactivity in first trimester and term placentae. In the first trimester,
      vascular endothelial growth factor immunoreactivity was localized to placental
      macrophages (Hofbauer cells), and in decidua, to glandular epithelium and
      maternal macrophages. In the term placenta, vascular endothelial growth factor
      immunoreactivity was present in extravillous trophoblast and in extracellular
      material. Flt immunoreactivity was demonstrated on extravillous trophoblast in
      first trimester and term, and on Hofbauer cells within placental villi. This
      complex pattern of both vascular endothelial growth factor and flt-like
      immunoreactivity suggests that vascular endothelial growth factor may be involved
      not only in the regulation of placental angiogenesis, but also in trophoblast
      invasion.

PMID- 8568763
TI  - Progesterone and oestrogen receptors in the decidualized mouse uterus and effects
      of different types of anti-progesterone treatment.
AB  - Pseudopregnant mice were treated systemically with monoclonal anti-progesterone
      antibody (DB3) (model 1), or progesterone receptor antagonists RU486 or ZK98,299
      (ZK299) (model 2) on day 3 post coitum. On day 4, sesame oil was administered
      intraluminally into one uterine horn to induce decidualization. On day 7, the
      average mass of the oil-injected horn was 335.2 +/- 52.4 mg, eight times greater
      than that of the non-injected horn (40.8 +/- 5.3 mg; P < 0.001). After treatment
      with DB3, RU486 or ZK299, the masses of the injected horns did not differ
      significantly from those of non-injected horns. In the control group,
      concentrations of progesterone receptors (ligand-binding assay) increased twofold
      in the decidualized (52.2 +/- 7.4 fmol mg-1) compared with the non-injected horn
      (26.0 +/- 7.6 fmol mg-1; P < 0.05), whereas oestrogen receptor content (ligand
      exchange assay) decreased by 53% (104.9 +/- 18.2 versus 224.3 +/- 18.1 fmol mg-1;
      P < 0.001). In model 1, antibody-treated animals showed a tenfold increase in the
      concentration of progesterone receptors (261.7 +/- 81.1 fmol mg-1; P < 0.001),
      but there was no differential distribution of progesterone or oestrogen receptors
      in the oil-injected versus non-injected uterine horns. In model 2, uterine
      progesterone and oestrogen receptors again showed no differential response
      between injected and non-injected horns regardless of the route of administration
      (systemic or intraluminal). Concentrations of progesterone receptors in RU486
      treated (35.8 +/- 9.4 fmol mg-1) and ZK299-treated (32.0 +/- 10.2 fmol mg-1) mice
      were comparable to those in non-injected horns (35.3 +/- 6.3 and 34.2 +/- 5.1
      fmol mg-1, respectively) and were not significantly different from the control
      group (26.0 +/- 7.6 fmol mg-1). The results show that oil-induced decidualization
      is accompanied by increased concentrations of progesterone receptors and
      decreased concentrations of oestrogen receptors. When decidualization is blocked
      by anti-progesterone treatment (antibody against progesterone or progesterone
      receptor antagonist), there are differing effects on receptor responses with an
      increase in progesterone receptors and decrease in oestrogen receptors after
      passive immunization, and no change in progesterone receptors and a reduction in
      oestrogen receptors after anti-progestins. The anti-decidualization effect in the
      two models was therefore achieved via dissimilar uterine receptor responses.

PMID- 8568764
TI  - Effect of semen storage on the number of spermatozoa in the perivitelline layer
      of laid turkey eggs.
AB  - A progressive decline in fertility over the course of egg production may be
      observed when turkey hens are inseminated weekly with semen stored for 24 h. In
      vitro storage of spermatozoa before insemination results in lower fertilization,
      possibly because fewer spermatozoa survive selection and storage in the hen's
      sperm storage tubules in vivo; alternatively, stored spermatozoa may be as
      capable of reaching the egg as are fresh spermatozoa, but unable to penetrate and
      fertilize the egg normally. The objective of this study was to determine whether
      this decline in fertility is a result of fewer spermatozoa reaching the egg after
      insemination with spermatozoa stored in vitro. Hens were inseminated weekly over
      the first 12 weeks of egg production with either fresh semen (n = 30 hens) or
      semen stored for 24 h (n = 30 hens). A total of 301 eggs was evaluated by
      determining the density distribution of spermatozoa embedded in the outer
      perivitelline layer. For the 12 weeks of egg production, the fertility of hens
      inseminated with fresh semen remained greater than 94%. Conversely, the
      percentage fertility of eggs from hens inseminated with stored semen in weeks 1-3
      was greater than 94% but thereafter fertility averaged 86%. There was no
      difference in hatchability of fertile eggs between the two treatments over all
      weeks combined, and weekly throughout the study (P > 0.05). The mean number of
      spermatozoa in the perivitelline layer was higher (P < 0.001) when hens were
      inseminated with fresh (12.1 +/- 1.3 spermatozoa per 5.5 mm2 membrane) versus
      stored semen (2.5 +/- 0.3 spermatozoa per 5.5 mm2 membrane) over all weeks
      combined, and weekly throughout the study (P < 0.05). As a result of storage for
      24 h, fewer spermatozoa are stored in the sperm storage tubules and,
      consequently, fewer spermatozoa are present at the site of fertilization, thus
      contributing to the depressed fertility.

PMID- 8568765
TI  - Maintenance of bovine oocytes in prophase of meiosis I by high [cAMP]i.
AB  - The effects of high intracellular cAMP concentrations ([cAMP]i) on germinal
      vesicle maintenance of bovine cumulus-oocyte complexes were investigated, using 8
      bromo-3',5'-cAMP (8-Br-cAMP) or an invasive adenylate cyclase from Bordetella
      pertussis to increase the [cAMP]i. The effects of interactions of these agents
      with macromolecular supplements in culture medium (fetal calf serum, FCS;
      polyvinylpyrrolidone, PVP; BSA), and different methods of processing complexes
      before culture, on subsequent germinal vesicle maintenance by invasive adenylate
      cyclase were studied. While 8-Br-cAMP was unable to maintain germinal vesicle
      arrest in the majority of oocytes for 20 h (36% with FCS, 24% with BSA, 18% with
      PVP), it maintained germinal vesicle arrest in a high proportion of cumulus
      enclosed oocytes when BSA or PVP was used (37% with FCS, 52% with BSA, 53% with
      PVP). The difference in frequency of germinal vesicle maintenance between
      macromolecular supplements was not related to [cAMP]i when assayed after culture
      for 2 h with invasive adenylate cyclase. Complexes processed in whole follicular
      fluid were not maintained in meiotic arrest (26%) when cultured with invasive
      adenylate cyclase and PVP. Complexes processed in follicular fluid with 3
      isobutyl 1-methylxanthine (IBMX) plus invasive adenylate cyclase were arrested at
      the germinal vesicle stage at high frequencies (65%), while those processed in
      IBMX or IBMX plus 8-Br-cAMP-supplemented follicular fluid had intermediate (43%
      and 49%, respectively) frequencies of intact germinal vesicles. Oocyte complexes
      processed in follicular fluid supplemented with IBMX and invasive adenylate
      cyclase formed morulae and blastocysts (27.2%), as did oocytes processed in
      follicular fluid alone (26%). Phosphoprotein profiles showed that control oocytes
      and 8-Br-cAMP-treated oocytes share a profile that is different from that of
      oocytes treated with invasive adenylate cyclase. These results show that
      increased [cAMP]i reversibly maintains bovine oocytes in meiotic arrest for an
      extended period without the occurrence of the post-translational protein
      modifications observed during meiotic resumption or transient arrest.

PMID- 8568766
TI  - Maintenance of meiotic arrest by increasing [cAMP]i may have physiological
      relevance in bovine oocytes.
AB  - Invasive adenylate cyclase (iAC) reversibly inhibits spontaneous maturation of
      cumulus-enclosed bovine oocytes by increasing the intracellular concentration of
      cAMP, [cAMP]i. In this study, physiological aspects of maintaining meiotic arrest
      in bovine oocytes by iAC were investigated. The maintenance of germinal vesicle
      arrest by iAC in both cumulus-enclosed and denuded bovine oocytes was
      concentration dependent (r2 = 0.857). Denuded bovine oocytes were more sensitive
      to maintenance of meiotic arrest by iAC then were cumulus-enclosed oocytes. At
      the highest concentration, 70% of the cumulus-enclosed and 90% of the denuded
      bovine oocytes were maintained in meiotic arrest. The iAC increased [cAMP]i in
      both intact cumulus-oocyte complexes and enclosed oocytes in a concentration
      dependent manner (r2 = 0.795). Cumulus-enclosed oocytes maintained in meiotic
      arrest by iAC retained developmental competence when subsequently cultured in iAC
      free medium and then fertilized. The [cAMP]i in bovine complexes decreased
      precipitously upon release from follicles and remained low for the next 125 min.
      However, the [cAMP]i of the enclosed oocytes did not change. Bovine oocytes
      commit to undergo meiosis in a progressive manner. Approximately 10% of the
      oocytes were already committed when aspirated. This proportion increased to 40%
      at 2 h and 70% at 5 h. Use of two inhibitors of cAMP-dependent protein kinase A
      provided further evidence that cAMP functions in mediating meiotic arrest in
      bovine oocytes. Bovine oocytes, therefore, are sensitive to different cAMP
      concentrations, and are developmentally competent after iAC-induced arrest, and
      complexes containing oocytes exhibit a decrease in [cAMP]i before spontaneous
      maturation. These results suggest that maintenance of meiotic arrest by iAC is
      accomplished through modulation of cellular machinery, and regulation of oocyte
      maturation by [cAMP]i may be physiologically relevant.

PMID- 8568767
TI  - Advanced ovulation in gilts by the intrauterine application of a low molecular
      mass pronase-sensitive fraction of boar seminal plasma.
AB  - The shortening of the time interval between the onset of oestrus and ovulation in
      sows by the transcervical administration of seminal plasma was investigated in 23
      German Landrace gilts, using the technique of single horn infusions (Mariensee
      model) in combination with the transcutaneous sonographic monitoring of ovaries.
      Preparative surgery comprised the detachment of the left uterine horn from the
      corpus, leaving the caudal end open to the peritoneal cavity but sealing the
      corpus wound. The left ovary was loosely tied to the ventral abdominal wall for
      better sonographic distinction. The animals were used in two to four consecutive
      cycles. After detection of oestrus by the teaser boar, the patent (right) horns
      were filled by transcervical infusion of 100 ml of a variety of test solutions.
      Ovulation was probed by transcutaneous sonography at intervals of 4 h thereafter.
      Native seminal plasma provoked ovulation in the ipsilateral ovary of the treated
      horn 10.7 h earlier than in the contralateral ovary. This effect was reduced to
      7.3 h after charcoal treatment of seminal plasma; addition of 10 micrograms
      oestradiol restored the effect in full, while 10 micrograms of oestradiol in PBS
      shortened the time interval to only 3.3 h versus the control ovary. Little effect
      was seen with oestrone sulfate, none with prostaglandins in PBS or with PBS
      alone. The preliminary characterization of the nonsteroidal component of seminal
      plasma advancing ipsilateral ovulation after transcervical infusion suggests a
      proteinaceous nature. The activity resides in the 1-10 kDa fraction separated by
      ultrafiltration and is lost after treatment with pronase.

PMID- 8568768
TI  - Changes in lipid peroxide and antioxidant enzyme activities in corpora lutea
      during pseudopregnancy in rats.
AB  - This study investigated the involvement of lipid peroxidation and antioxidant
      enzymes in the regulation of luteal function in pseudopregnant rats. The
      activities of superoxide dismutase (SOD), a specific scavenger of superoxide
      radicals, and glutathione peroxidase, a scavenger of hydrogen peroxide, and lipid
      peroxide concentrations were measured in the corpus luteum on days 1, 3, 5, 7, 9,
      11 and 13 of pseudopregnancy. The activity of SOD in the corpus luteum gradually
      increased until day 9 of pseudopregnancy and decreased thereafter, in a similar
      manner to serum progesterone concentration. Glutathione peroxidase activity
      significantly increased from day 1 to day 3 and remained high until day 11 of
      pseudopregnancy. The concentrations of lipid peroxides in the corpus luteum
      increased from day 3 to day 13 of pseudopregnancy. The involvement of
      prostaglandin F2 alpha (PGF2 alpha) in the production of lipid peroxides in
      regression of the corpus luteum was investigated by administering PGF2 alpha (3
      mg kg-1, s.c.) or saline on days 7, 9 and 12 of pseudopregnancy. Each group of
      rats was autopsied 2 h later, and SOD activity, glutathione peroxidase activity
      and the concentration of lipid peroxides in the corpus luteum were determined.
      PGF2 alpha significantly increased lipid peroxide concentrations in the corpus
      luteum on days 7, 9 and 12 of pseudopregnancy (approximately twofold increases on
      days 7 and 9, and a fivefold increase on day 12, compared with the control that
      received saline). The activity of SOD in the corpus luteum was significantly
      increased by PGF2 alpha on days 7 and 9, but not on day 12, of pseudopregnancy.
      PGF2 alpha did not cause any significant changes in glutathione peroxidase
      activity in the corpus luteum on days 7, 9 and 12 of pseudopregnancy. It is
      concluded that lipid peroxides play an important role in regulating luteal
      function in pseudopregnant rats.

PMID- 8568769
TI  - Blood vessel growth and endothelial cell density in rat endometrium.
AB  - The aim of the present study was to quantify endothelial cell density in rat
      endometrium during early pregnancy (a time of increased endothelial cell
      proliferation), using immunohistochemical methods. Despite the occurrence of
      vessel growth, the endometrial endothelial cell density remained unchanged before
      embryo implantation, indicating that endothelial cell proliferation keeps pace
      with proliferation of the surrounding endometrial cells. After implantation,
      endothelial cell density falls at embryo sites on day 6, despite very high
      endothelial cell proliferation rates. This is probably due to the oedema caused
      by the localized increase in vascular permeability at implantation sites. We
      hypothesize that this reduction may provide a stimulus for the observed
      endothelial cell proliferation, rather than a direct angiogenic stimulus from the
      embryo.

PMID- 8568770
TI  - Effects of chronic treatment with a gonadotrophin-releasing hormone agonist on
      peripheral concentrations of FSH and LH, and ovarian function in heifers.
AB  - The effect of chronic treatment with a gonadotrophin-releasing hormone agonist
      (GnRHa) on ovarian function in cattle was investigated by injecting heifers i.m.
      twice a day with saline, 5 micrograms GnRHa (Buserelin) or 10 micrograms GnRHa (n
      = 7) for 21 days. Blood samples were taken twice a day during the treatment
      period, and then three times a day for 7 days and once daily for a further 4
      days. Frequent samples were also collected on day 1, day 10 and day 21 of
      treatment. The ovaries of all heifers were examined daily using real-time
      ultrasonography throughout the experimental period. No significant differences in
      the response were observed between two doses of GnRHa. The first GnRHa injection
      produced a large LH and FSH surge and this acute response was still present by
      day 21 of treatment, but both the magnitude and duration of response were
      significantly attenuated (P < 0.01). After an initial increase, LH returned to
      the basal concentration, which was maintained until the termination of treatment,
      when concentrations increased significantly, with a preovulatory surge occurring
      approximately 6 days later. Peripheral FSH concentrations during the oestrous
      cycle in control animals displayed a pattern of three waves, each of which
      closely preceded a wave of follicular development. Concentrations of FSH in GnRHa
      treated heifers showed a normal pattern for the first wave after the start of
      treatment. During the next wave, concentrations increased and remained at the
      peak values until about 4 days after the end of treatment. An additional
      ovulation was induced in 11 of 14 GnRHa-treated heifers within 2-3 days of the
      start of treatment, and a significant (P < 0.05) increase in serum progesterone
      concentrations was detected 2 days later. All GnRHa-treated heifers then showed a
      normal follicular wave, with the development and regression of a dominant
      follicle. The dominant follicles from the next wave grew to only 7-9 mm in
      diameter and remained at this size until the end of treatment, when they resumed
      growth, ovulated approximately 7 days later and formed corpora lutea. We conclude
      that chronic treatment of heifers with GnRHa for 3 weeks suppresses pulsatile
      secretion of LH and blocks the development of dominant follicles beyond 9 mm in
      diameter, preventing the preovulatory LH surge and ovulation. However, GnRHa did
      not suppress the secretion of FSH within the 3 week treatment period. The
      maintenance of the dominant follicles for an extended period should provide an
      ideal model to study the control of follicular atresia in cattle in vivo.

PMID- 8568771
TI  - Ageing, infecundity and reproductive senescence in free-ranging female rhesus
      monkeys.
AB  - The reproductive performance of 760 free-ranging female rhesus monkeys (Macaca
      mulatta), 168 of whom were 20 years of age and older at the time observations
      were begun, was assessed. The monkeys were resident on Raccoon Key or Key Lois,
      two islands located in the Florida Keys, USA. During 1992 and 1993, live birth
      rates generally declined with age among the Raccoon and Lois females aged eight
      years and older. This age-related deterioration of female fertility was the
      result of proportionately more younger females bearing live young during
      successive birth seasons, and proportionately more older females experiencing an
      inability to bear live offspring even after a barren year. It is suggested that
      (1) older females may be more strongly inhibited by the suckling stimulus than
      are their younger peers, and (2) the risk of a permanent loss of fecundity
      increases with each additional year of life or parturition. The live birth rates
      of females aged 16-24 years were greater on Raccoon Key than they were on Key
      Lois, because the Raccoon females within this age range were more successful at
      bearing live offspring during successive birth seasons; the reason for this
      difference could not be determined. Inter-population differences in both the body
      condition of the females and the severity of female-female competition for access
      to males were not considered to be plausible explanations. It is possible that
      the difference in female fertility between the islands is the result of the
      greater age of the adult males on Key Lois, or the phytochemicals eaten by the
      females on Raccoon Key.

PMID- 8568772
TI  - Long-term influence of sialoadenectomy on reproductive performance of male mice.
AB  - The influence of the submandibular gland, the major source of epithelial growth
      factor, on male reproduction in mice was studied by removing the submandibular
      gland (sialoadenectomy) and examining its effects on sperm production and
      copulation and fertility rates over an extended post-operation period. The
      removal of the submandibular gland caused a decrease in the number of epididymal
      spermatozoa 4 weeks after the operation; the decrease became significant (P <
      0.05) 6-10 weeks after the operation compared with the sham operated and intact
      groups. There was no significant difference between prepuberal (30 days old) and
      postpuberal (60 days old) sialoadenectomy, indicating that the submandibular
      gland is not related to the maturation of the seminiferous tubules. The reduction
      in the number of epididymal spermatozoa was due to the decrease in number of
      spermatogonia and spermatocytes per Sertoli cell in the seminiferous tubules.
      When the reproductive performance was examined over 14 weeks, sialoadenectomized
      males showed a lower copulation rate and a significantly (P < 0.05) higher
      incidence of non-fertile copulation compared with the sham-operated and intact
      males. These results indicate that the submandibular gland and the secretion of
      epithelial growth factor from it affect spermatogenesis by acting on
      spermatogonial proliferation and sperm maturation.

PMID- 8568773
TI  - Morphology of pig uterine subepithelial capillaries after topical and systemic
      oestrogen treatment.
AB  - The ultrastructure of subepithelial capillaries in pig endometrium was studied
      after intrauterine and systemic oestradiol treatment. Gilts were killed on day 13
      or 19 (n = 4 per day per treatment) after surgical introduction of Silastic beads
      containing either oestradiol or cholesterol into the uterine lumina on day 10
      after oestrus. An additional group of gilts was injected i.m. with 5 mg
      oestradiol valerate on days 11-15 of the oestrous cycle and killed on day 13 or
      day 19 (n = 4 per day). Light and electron microscope studies of endometrial
      samples revealed that cholesterol beads did not appear to affect subepithelial
      capillary structure. Both intrauterine and systemic treatment of gilts with
      oestradiol were associated with regional modification of the capillary wall
      involving attenuation and fenestration of the face directly underlying the
      uterine epithelium, accumulation of caveolae in the opposite face of the
      capillary, and the occurrence of discontinuous, multilayered capillary basal
      laminae. The similarity of these structural changes to those observed in
      capillaries at the time of embryonic attachment suggests that oestrogens of
      blastocyst origin may function to modify capillary morphology and possibly
      facilitate increased transcapillary traffic during the establishment of
      pregnancy.

PMID- 8568774
TI  - Analysis of an epitope sequence recognized by a monoclonal antibody MAb-5H4
      against a porcine zona pellucida glycoprotein (pZP4) that blocks fertilization.
AB  - The zona pellucida glycoprotein that surrounds the mammalian oocyte has several
      target antigens that have potential use in the development of a contraceptive
      vaccine. In the present study, an epitope sequence recognized by a monoclonal
      antibody to the porcine zona pellucida glycoprotein ZP4 was determined. Three
      candidate peptides were synthesized, based on an epitope mapping by cDNA and an
      analysis of chain flexibility of porcine ZP4. Only one synthetic peptide,
      corresponding to amino acid positions 50-67, reacted with the monoclonal
      antibody; the other synthetic peptides, corresponding to positions 60-79 and 70
      100, did not react. The reactive epitope was identified as CTYVLDPENL,
      corresponding to positions 50-59 of porcine ZP4. The peptide inhibited the
      reaction of the monoclonal antibody binding to native ZP4 in a dose-dependent
      manner. When the synthetic peptide 50-67 was used to immunize mice, the resultant
      antisera reacted not only with the synthetic peptide but also with native pig
      zona pellucida. In addition, anti-peptide 50-67 antibody inhibited porcine
      fertilization in vitro. It is thus concluded that the peptide identified as an
      epitope for the monoclonal antibody would be a promising candidate for the
      development of a contraceptive vaccine.

PMID- 8568775
TI  - Nitric oxide synthase inhibition and the uterotrophic response to oestrogen in
      immature rats.
AB  - The role of nitric oxide in the uterotrophic action of oestradiol after 6 h or 72
      h was studied in immature (19-21 days old) female Wistar rats by use of L
      arginine, the amino acid from which nitric oxide is synthesized, and N omega
      nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase.
      Oestradiol at single s.c. doses of 2.5, 5.0 and 10.0 micrograms per rat induced
      dose-dependent uterine oedema in 6 h. L-NAME (10 and 20 mg kg-1, i.p.)
      administered 30 min before oestradiol (10 micrograms per rat) injection
      suppressed the formation of uterine oedema in a dose-related manner. This action
      of L-NAME on oestradiol-induced uterine oedema was effectively blocked by
      pretreatment of rats with L-arginine (600 mg kg-1, s.c.), a precursor of nitric
      oxide, but not by L-lysine, an amino acid not involved in the generation of
      nitric oxide. In addition, L-NAME at similar doses significantly prevented
      oestradiol-induced (3 micrograms per rat, s.c. on three successive days)
      increases in uterine growth after 72 h; however, this effect was mitigated by L
      arginine (600 mg kg-1). These results suggest the involvement of an L-arginine
      nitric oxide system in the oestradiol-induced uterotrophic effect in immature
      rats.

PMID- 8568776
TI  - Plasma concentrations of progesterone, oestradiol, LH and 15-ketodihydro-PGF2
      alpha in Norwegian semi-domestic reindeer (Rangifer tarandus tarandus) during
      their first reproductive season.
AB  - Blood samples were collected from eleven 1.5 year old female reindeer three times
      a week from September 1992 until February 1993 and daily in October and November
      1992. Blood samples were collected every third hour for a period of three weeks
      from two females that showed regular oestrous cycles. Plasma progesterone,
      oestradiol, LH and 15-ketodihydro-PGF2 alpha were analysed to characterize
      variations in ovarian function. Reindeer are seasonally polyoestrous. Average
      duration of oestrous cycles was 19.4 days (range: 13-33 days). Short periods of
      high progesterone concentrations (4-8 days duration) occurred in five animals
      before the onset of regular oestrous cycles. The first regular cycle had a
      significantly longer luteal phase than did the following cycles. During
      luteolysis 15-ketodihydro-PGF2 alpha was released in a pulsatile pattern. Maximal
      oestradiol concentrations preceded preovulatory LH peaks by about 3 h in the two
      frequently sampled animals. The duration of LH surges was 12 and 15 h,
      respectively.

PMID- 8568777
TI  - Differential metabolism of exogenous platelet-activating factor by glandular
      epithelial and stromal cells of rabbit endometrium.
AB  - Significant changes in platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn
      glycero-3-phosphorylcholine) concentration have been observed in rabbit
      endometrium during the preimplantation period, but, under in vitro conditions,
      constitutive PAF biosynthesis by isolated endometrial tissues was not easily
      demonstrable. Relative changes in enzymes involved in the synthesis and
      metabolism of PAF in the tissues may account for this disparity. In addition,
      during this period of preimplantation, marked changes in PAF receptor
      concentration have been noted. The present study examines the factors that may
      modulate the metabolism of exogenous [3H]PAF in the endometrium of rabbits on day
      6 of pregnancy. Since preferential [3H]PAF binding in situ by the glandular
      epithelial, but not by the stromal, cells was demonstrated, their cell-specific
      metabolism of exogenous [3H]PAF was also examined. After entry into the
      endometrial cell, [3H]PAF was rapidly metabolized by the sequential action of
      cytosolic Ca(2+)-independent acetylhydrolase to [3H]lyso-PAF and this was in turn
      acylated by membrane-associated transacylase to [3H]alkylacyl
      glycerylphosphorylcholine. PAF resynthesis was not observed and, in stromal
      cells, there was a significant build-up of [3H]lyso-PAF, suggesting that lyso
      PAF:acetyl-CoA acetyl-transferase may be a limiting factor. In the glandular
      epithelial cells, however, there was a significant accumulation of a neutral
      lipid without a significant build-up of [3H]lyso-PAF or [3H]PAF. The neutral
      lipid co-migrated with the product of phospholipase C-catalysed metabolism of PAF
      and authentic 1-O-hexadecyl-2-acetyl-glycerol. In addition, the elution times of
      phospholipase C digestion of C18 PAF and the neutral lipid produced by cellular
      metabolism of [3H]PAF, determined by gas chromatography/flame ionization
      detection, were similar. It seems that it is the synthesis of the neutral lipid
      from reacetylated [3H]lyso-PAF that prevented [3H]PAF accumulation under in vitro
      conditions. This is the first documentation of the synthesis of this lipid in the
      mammalian uterus. The lipid may serve as the precursor for de novo PAF synthesis
      in the glandular epithelial cells during endometrial proliferation.

PMID- 8568778
TI  - Decrease of histone H1 kinase activity in relation to parthenogenetic activation
      of pig follicular oocytes matured and aged in vitro.
AB  - Changes of histone H1 kinase activity before and after electrical stimulation
      were connected with the ability of cytoplasm of pig oocytes to be activated
      parthenogenetically when matured and aged in vitro. Cumulus-oocyte complexes were
      collected from prepubertal gilts and cultured in a modified Waymouth's MB752/1
      medium. The first mature oocytes were observed after 30 h of culture. After 36 h
      of culture, about 65% of oocytes had matured (reached metaphase II stage with the
      first polar body). When oocytes matured after 36 h of culture were stimulated
      with an electric pulse and subsequently cultured for 10 h, only 7% became
      parthenogenetically activated (formation of a female pronucleus). When oocytes
      matured for 60 h and 72 h underwent the same treatment, significantly more became
      activated parthenogenetically (46% and 57%, respectively). Oocytes matured for 72
      h but not stimulated electrically also exhibited high spontaneous parthenogenetic
      activation (24%). Activation of oocytes resulted either in the formation of a
      female pronucleus(ei) or in fragmentation of oocytes. Fragmentation in stimulated
      and nonstimulated oocytes increased significantly after 72 h of culture (37% and
      18%, respectively). Histone H1 kinase activity in immature oocytes at the
      germinal vesicle stage was low (17.2 fmol h-1 per oocyte). However, when oocytes
      were cultured for 36 and 48 h, histone H1 kinase activity increased significantly
      (168.2 and 138.5 fmol h-1 per oocyte, respectively). Prolonged culture (60 h and
      72 h) resulted in a significant decrease in histone H1 kinase activity (94.3 and
      49.3 fmol h-1 per oocyte, respectively). When oocytes cultured for up to 72 h
      were electrically stimulated, histone H1 kinase activity in activated oocytes
      (oocytes that formed a female pronucleus and fragmented oocytes) was
      significantly lower (24.7 mol h-1 per oocyte) than that in nonactivated oocytes
      (99.9 mol h-1 per oocyte). The present data clearly indicate that the gradual
      decrease of histone H1 kinase activity is correlated with ageing of oocytes
      matured in vitro and with their ability to be parthenogenetically activated.

PMID- 8568780
TI  - Lead toxicity and public health policy.
AB  - Senior UK scientists have recently acknowledged that lead exerts neurotoxic
      effects at blood lead levels even as low as 10 micrograms/dL. The implications of
      these findings for public policy are outlined, especially in relation to
      contamination of drinking water, soil and household dust. Estimates of the
      proportion of 6 year old children with elevated blood lead levels for several
      locations are also provided.

PMID- 8568779
TI  - Trophic effects of myeloid leukaemia inhibitory factor (LIF) on mouse embryos.
AB  - Myeloid leukaemia inhibitory factor (LIF) is expressed at highest concentrations
      in the maternal endometrial glands at about the stage of blastocyst implantation.
      LIF is also expressed by the extraembryonic membranes of the early mouse embryo.
      Embryos of different ages were cultured with, or without, LIF, and embryo growth
      in vivo and in vitro was examined to determine whether LIF is important for
      embryo development. Supplementing embryo culture media with 1000 U recombinant
      human LIF ml-1 increased the number of eight-cell mouse embryos developing beyond
      the hatched blastocyst stage in vitro from 62.1% to 85.1% (P < 0.05). LIF
      significantly increased the number of embryos hatching (33.8% versus 7.65% for
      controls 96 h after hCG injection, P < 0.001), completely hatching (85.1% versus
      62.1%, P < 0.05), and exhibiting trophoblast outgrowth (13.5% versus 0% 120 h
      after hCG treatment, 85.1% versus 47.0% 144 h after hCG treatment, P < 0.001) in
      vitro. LIF-treated embryos also displayed a significantly greater area of
      trophoblast outgrowth than did controls as early as day 5 in culture (P < 0.005).
      These data show that LIF enhances mouse eight-cell embryo development in vitro,
      as seen by the accelerated rate of embryo hatching and trophoblast outgrowth. In
      addition, enhanced embryo survival in vivo is shown, following the transfer of
      LIF-treated embryos into a pseudopregnant recipient female. Expression of mRNA
      encoding LIF was detected in endometrial cells cultured in monolayer from uteri
      of day 3 pregnant females, explaining the known embryotrophic effects of
      endometrial coculture. This expression was not enhanced significantly by
      treatment with oestradiol (3.7 x 10(-5) mol l-1) or progesterone (3.2 x 10(-6)
      mol l-1) or both hormones. These results indicate that LIF could have a dual
      action in early embryogenesis as an embryotrophin and as a factor required for
      embryo implantation. Multiple roles for LIF are consistent with the expression of
      this factor at embryonic, extraembryonic and maternal sites during early
      embryogenesis.

PMID- 8568781
TI  - Immediacy concept application in the teaching of courses in environmental health.
AB  - Immediacy, a communication behaviour, is defined and its application in the
      teaching of environmental health courses is illustrated. The practical experience
      gained from engaging in this teaching behaviour includes enhancement of student
      professor relationships, affective learning and increased sensory stimulation,
      etc. The dynamics of this concept are exemplified in this article.

PMID- 8568783
TI  - The role of UK tobacco advertising: no effect on the nation's health? Part II:
      The political economy and marketing of tobacco.

PMID- 8568782
TI  - Cigarette smoking and health of the heart.
AB  - A large series of studies relate cigarette smoking to the development of
      cardiovascular damage. Both active and passive smoking seem to act negatively on
      the heart, although with different results. Active smoking impairs the
      cardiovascular system chronically causing mainly coronary atherosclerosis,
      whereas passive smoking impairs cardiac performance transiently after acute
      exposure, and to a greater extent in those with established ischaemic heart
      disease. Evidence indicates that the heart is a target organ for cigarette
      smoking (Leone, 1992). Diseases of the heart and blood vessels account for over
      one-third of all the excess deaths in smokers (follow-up report of the Royal
      College of Physicians, 1983). The purpose of this report is to demonstrate some
      of the links between cardiovascular damage and smoking by reviewing our previous
      findings based on an Italian population.

PMID- 8568784
TI  - Towards malaria control in Nigeria: a qualitative study on the population of
      mosquitoes.
AB  - Malaria is still highly prevalent in many tropical countries and this disease can
      only survive in areas where mosquitoes and infected human populations are high.
      Relevant information on the species of mosquitoes, their habitats and their
      population are important in planning preventative strategies in the control of
      malaria, hence this study. Mosquito species and their habitats were investigated
      in both high and low density areas of Benin City, Edo State, Nigeria. The results
      showed that Culex pipiens fatigans, Aedes aegypti, Aedes albopictus, Anopheles
      gambiae and Culex trigripes were the commonest mosquitoes found in Benin City.
      Among the habitats studied, containers and gutters had the highest population of
      mosquitoes. The serious public health implications of these various species of
      mosquitoes is the possibility of outbreaks of infectious diseases like yellow
      fever, dengue, which some of these mosquitoes are known to transmit. Malaria,
      though endemic, is also important because of its associated high morbidity and
      mortality rates. This study provides some useful information on the habitats and
      species of mosquitoes found in Benin City. Follow-up studies are being carried
      out by the authors on quantitative studies on the population of these species of
      mosquitoes, the dissolved elements present in the different habitats that could
      promote or inhibit the breeding of mosquitoes, and KAP surveys on mosquitoes and
      malaria among the Benin populace. It is hoped that such comprehensive data would
      be very useful in planning effective preventative strategies in the control of
      malaria in Benin City.

PMID- 8568785
TI  - Breakfast cereal consumption patterns and nutrient intakes of British
      schoolchildren.
AB  - Breakfast cereals are nutrient-dense foods that are also low in fat. They could
      theoretically contribute to lowering the percentage energy from fat in the diet
      whilst enhancing the intake of certain nutrients. This project is based on a
      further analysis of dietary data (seven day weighed intakes) from 2705 British
      schoolchildren (DoH, 1989) and examines the relationship between breakfast cereal
      consumption and total daily nutrient intakes. The children were grouped according
      to amount of cereal consumed per day (none; less than 20 g; 20-40 g; over 40 g)
      and results examined for each age group (10-11 and 14-15 years) in boys and girls
      separately. For the nutrients examined there was a highly significant and graded
      increase in vitamin and mineral intake with increasing cereal consumption and a
      simultaneous reduction in energy from fat from 39-40% amongst non-consumers to 36
      37% among children consuming a portion of cereal or more per day. Body mass index
      tended to be lower in the frequent breakfast cereal eaters. In conclusion,
      children who eat breakfast cereal tend to have more desirable nutrient intakes
      than those who do not.

PMID- 8568786
TI  - Assessment of radon levels in soil and water.
AB  - Radon gas and its progeny are radioactive and may induce lung cancer. A main
      source of indoor radon concentration is the radon gas which comes from the soil
      under a house or building. Therefore, accurate measurement of the radon
      concentrations in the soil are very helpful in identifying doubtful areas and in
      minimizing some radon hazards. A method of assessing the radon concentration in
      soil is described. The results were compared with the radon concentrations in
      associated water samples. It was found that the concentrations in soil and water
      were correlated, except for some anomalies and that the measurement of
      concentrations in soil were more direct and sensitive.

PMID- 8568787
TI  - Health status of cement workers in the United Arab Emirates.
AB  - The aim of this study was to investigate some of the health problems among cement
      workers in the United Arab Emirates (UAE). A cross-sectional sample of 304
      workers was selected randomly from four cement factories in four Emirates. Most
      of the workers (88%) were from India, married (84%) and had received primary
      education or above (93%). Smoking was prevalent among 27% of the workers and
      about 24% consumed alcoholic beverages. Personal hygiene was found to be
      satisfactory among the workers. The main health symptoms reported by the cement
      workers were chronic cough, chronic bronchitis, burning, itching and runny eyes,
      headache and fatigue. Chronic bronchitis (p < 0.007), burning, itching and runny
      eyes (p < 0.002) and fatigue (p < 0.004) were significantly increased with age of
      workers. Smoking was significantly associated with chronic cough (p < 0.03) and
      chronic bronchitis (p < 0.01). However, the chance of smokers getting respiratory
      health problems was two to five times greater compared with non-smokers. Future
      studies on the health of workers in UAE should include more investigations using
      specialised equipment to detect and diagnose health problems.

PMID- 8568788
TI  - Simulation modelling for resource allocation and planning in the health sector.
AB  - This paper provides a review of the use of simulation for resource planning in
      the health sector. Case examples of simulation in health are provided, and the
      modelling problems are explored. The successes and failures of simulation
      modelling in this context are examined, and an approach for improving the
      processes, and outcomes, by the use of soft systems methodology, is suggested.

PMID- 8568789
TI  - Job satisfaction in public health: a comparative analysis of five occupational
      groups.
AB  - Five occupational groups of public health workers (health administrators, nursing
      personnel, environmental health personnel, other public health workers, and
      public health support staff) from nine county health departments in the
      midwestern United States were statistically compared to uncover similarities and
      differences in job satisfaction/dissatisfaction that might be important in
      planning effective intervention programmes designed to improve satisfaction on
      the job. Each participant in the study (n = 602) completed three validated job
      satisfaction/dissatisfaction instruments: the Job Descriptive Index, the Job in
      General scale and the Occupational Needs Questionnaire. Several discernable
      trends in job satisfaction/dissatisfaction were identified among the groups. In
      general, health administrators appeared to be more satisfied with their jobs
      compared to the other groups, especially with regard to the actual work
      performed. Public health support staff, on the other hand, seemed to be the least
      satisfied group, particularly with respect to pay. The greatest source of
      dissatisfaction among all the groups appeared to be the lack of promotional
      opportunities.

PMID- 8568791
TI  - Aluminium and possible alarming health hazards.

PMID- 8568790
TI  - Dealing with drug misuse.
AB  - This paper provides a background to current trends in the treatment of drug
      misuse in the UK. It presents an argument for adopting a client-centred approach
      emphasising harm minimisation, as a means of reducing the negative impact of drug
      misuse behaviour on the community, particularly in housing estates. The paper
      concentrates on opiate misuse as this currently presents the greatest challenge
      to society in the UK, although the use of cocaine and other stimulants is on the
      increase.

PMID- 8568792
TI  - Fashions in illnesses.

PMID- 8568793
TI  - Drugs in the human environment.

PMID- 8568794
TI  - Essential food hygiene on CD-ROM. A new dimension in food hygiene training.

PMID- 8568795
TI  - The view from inside the receptor.

PMID- 8568797
TI  - Synthesis and structure-activity relationships of phenylenebis(methylene)-linked
      bis-tetraazamacrocycles that inhibit human immunodeficiency virus replication. 2.
      Effect of heteroaromatic linkers on the activity of bicyclams.
AB  - A series of bicyclam analogs connected through a heteroaromatic linker have been
      synthesized and evaluated for their inhibitory effects on HIV-1 (IIIB) and HIV-2
      (ROD) replication in MT-4 cells. The activity of pyridine- and pyrazine-linked
      bicyclams was found to be highly dependent upon the substitution of the
      heteroaromatic linker connecting the cyclam rings. For example, 2,6- and 3,5
      pyridine-linked bicyclams were potent inhibitors of HIV-1 and HIV-2 replication,
      whereas the 2,5- and 2,4-substituted pyridine-linked compounds exhibited
      substantially reduced activity and, in addition, were found to be highly toxic to
      MT-4 cells. We have subsequently discovered that these effects are not unique;
      amino-substituted linkers also have the potential to deactivate
      phenylenebis(methylene)-linked bicyclams. A model is proposed to explain the
      deactivating effects of the pyridine group in certain substitution patterns based
      on the ability of the pyridine nitrogen to participate in pendant conformations
      (complexation) with the adjacent azamacrocyclic ring, which may involve hydrogen
      bonding or coordination to a transition metal. The introduction of a sterically
      hindering group such as phenyl at the 6-position of the 2,4-substituted pyridine
      linked bicyclam appears to prevent pendant conformations, providing an analog
      with comparable anti-HIV-1 and anti-HIV-2 activities to the parent m
      phenylenebis(methylene)-linked bicyclam. The results of this study have been used
      to develop a quantitative structure-activity relationship model with improved
      predictive capability in order to aid the design of antiviral bis-azamacrocyclic
      analogs.

PMID- 8568796
TI  - Discovery of the hemifumarate and (alpha-L-alanyloxy)methyl ether as prodrugs of
      an antirheumatic oxindole: prodrugs for the enolic OH group.
AB  - Ether, ester, and carbonate derivatives of the antirheumatic oxindole 1 were
      prepared and screened as potential prodrugs of 1. This effort led to the
      discovery of the (alpha-L-alanyloxy)-methyl ether and hemifumarate derivatives of
      1 which deliver the drug efficiently into the circulation of test animals, are
      stable in the solid state, and possess good stability in solution at low pH as
      required to ensure gastric stability. Success in achieving acceptable
      bioavailabilities of 1 across species (rats, dogs, and monkeys) followed the
      inclusion of ionizable functionality within the promoiety to compensate for
      masking the polar enolic OH group of the free drug. However, the introduction of
      ionizable functionality was often associated with decreased stability, as
      demonstrated by the hemisuccinate, hemiadipate, hemisuberate, and alpha-amino
      ester derivatives of 1 which could not be isolated. A clear exception was the
      hemifumarate derivative of 1 which was not only isolable but actually more stable
      at neutral pH than the nonionizable ester analogues. The solution and solid state
      stability of the hemifumarate, together with its activity as a prodrug of 1,
      suggests that hemifumarate be considered as an alternative to hemisuccinate as a
      prodrug derivative for alcohols, particularly in situations where solution state
      stability is an issue.

PMID- 8568798
TI  - Biarylcarboxylic acids and -amides: inhibition of phosphodiesterase type IV
      versus [3H]rolipram binding activity and their relationship to emetic behavior in
      the ferret.
AB  - In addition to having desirable inhibitory effects on inflammation, anaphylaxis,
      and smooth muscle contraction, PDE-IV inhibitors also produce undesirable side
      effects including nausea and vomiting. In general, compounds that inhibit PDE-IV
      also potently displace [3H]rolipram from a high-affinity binding site in rat
      cortex. While this binding site has not been identified, it has been proposed to
      be an allosteric binding site on the PDE-IV enzyme. Preliminary studies have
      suggested that the emetic potency of PDE-IV inhibitors is correlated with
      affinity for the brain rolipram binding site rather than potency at inhibiting
      PDE-IV enzyme activity. Efforts to eliminate the emetic potential of PDE-IV
      inhibitors were directed toward developing compounds with decreased [3H]rolipram
      binding affinity while retaining PDE-IV potency. Thus, a novel series of 4-(3
      alkoxy-4-methoxyphenyl)benzoic acids and their corresponding carboxamides were
      prepared and evaluated for their PDE-IV inhibitory and rolipram binding site
      properties. Modification of the catechol ether moiety led to phenylbutoxy and
      phenylpentoxy analogues that provided the desired activity profile. Specifically,
      4-[3-(5-phenylpentoxy)-4-methoxyphenyl]-2-methylbenzoic acid, 18, was found to
      exhibit potent PDE-IV inhibitory activity (IC50 0.41 microM) and possessed 400
      times weaker activity than rolipram for the [3H]rolipram binding site. In vivo,
      compound 18 was efficacious in the guinea pig aerosolized antigen induced airway
      obstruction assay (ED50 8.8 mg/kg, po) and demonstrated a significant reduction
      in emetic side effects (ferret, 20% emesis at 30 mg/kg, po).

PMID- 8568799
TI  - Binding of arylpiperazines, (aryloxy)propanolamines, and tetrahydropyridylindoles
      to the 5-HT1A receptor: contribution of the molecular lipophilicity potential to
      three-dimensional quantitative structure-affinity relationship models.
AB  - A set of 280 5-HT1A receptor ligands were selected from available literature data
      according to predefined criteria and subjected to three-dimensional quantitative
      structure-affinity relationship analysis using comparative molecular field
      analysis. No model was obtained for serotonin analogues (19 compounds) and
      aminotetralins (60 compounds), despite a variety of alignment hypotheses being
      tried. In contrast, the steric, electrostatic, and lipophilicity fields alone and
      in combination yielded informative models for arylpiperazines (101 training
      compounds and 12 test compounds), (aryloxy)propanolamines (30 training compounds
      and four test compounds), and tetrahydropyridylindoles (54 training compounds)
      taken separately (models A, B, and C). Arylpiperazines and
      (aryloxy)propanolamines were then combined successfully to yield reasonably good
      models for 131 compounds (model D). In a last step, the three chemical classes
      (185 compounds) were combined, again successfully (model E). This stepwise
      procedure not only ascertains self-consistency in alignments but it also allows
      statistical signals (i.e., favorable or unfavorable regions around molecules) to
      emerge which cannot exist in a single chemical class. The models so obtained
      reveal a number of interaction sites between ligands and the 5-HT1A receptor, and
      extend the information gathered from a model based on homology modeling.

PMID- 8568800
TI  - Structure-antigastrin activity relationships of new spiroglumide amido acid
      derivatives.
AB  - A series of new spiroglumide amido acid derivatives was synthesized and evaluated
      for their ability to inhibit the binding of cholecystokinin (CCK) to guinea pig
      brain cortex (CCKB receptors) and peripheral rat pancreatic acini (CCKA
      receptors), as well as to inhibit in vitro the gastrin-induced Ca2+ increase in
      rabbit gastric parietal cells. Appropriate chemical manipulations of the
      structure of spiroglumide (CR 2194), i.e., (R)-4-(3,5-dichlorobenzamido)-5-(8
      azaspiro[4.5]decan- 8-yl)-5-oxopentanoic acid, led to potent and selective
      antagonists of CCKB/gastrin receptors. Structure-activity relationships are
      discussed. Some of these new derivatives, as, for example, compound 54 (CR 2622),
      i.e., (S)-4-[[(R)-4'-[(3,5-dichlorobenzoyl)-amino]-5'-(8- azaspiro[4.5]decan-8
      yl)-5'-oxo-pentanoyl]amino]-5- (1-naphthylamino)-5-oxopentanoic acid, exhibit
      activity 70-170 times greater than that of spiroglumide, depending upon the model
      used (IC50 = 2 x 10(-8) vs 140 x 10(-8) mol in binding inhibition of [3H]-N-Me-N
      Leu-CCK-8 in guinea pig brain cortex and IC50 = 0.7 x 10(-8) vs 122.3 x 10(-8)
      mol in inhibition of gastrin-induced Ca2+ mobilization in parietal cells of
      rabbit, respectively). Computer-assisted conformational analysis studies were
      carried out in order to compare the chemical structure of both the agonist
      (pentagastrin) and the antagonist (54).

PMID- 8568801
TI  - 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic
      agents.
AB  - A series of substituted phenethyl derivatives of 3-benzisothiazolylpiperazine
      incorporating potent D2 and 5-HT2A antagonist activity was investigated as an
      approach to a novel atypical antipsychotic agent. The in vitro profile of 8e from
      this series is a combination of D2 receptor affinity comparable to the typical
      antipsychotic agent haloperidol and a 5-HT2A/D2 ratio comparable to the atypical
      agent clozapine. In vivo 8e possesses activity consistent with an efficacious
      antipsychotic agent with less tendency to induce extrapyramidal side effects in
      man.

PMID- 8568802
TI  - Effect of linking bridge modifications on the antipsychotic profile of some
      phthalimide and isoindolinone derivatives.
AB  - A series of phthalimide and isoindolinone derivatives bridged to 4-(1,2
      benzisothiazol-3-yl)-1-piperazinyl was prepared. The compounds were evaluated in
      vitro at dopamine D2 and serotonin 5-HT1a and 5-HT2 receptors and in vivo for
      their ability to antagonize the apomorphine-induced climbing response in mice.
      The effects of bridge length and conformation on the biological activity of these
      potential antipsychotic agents are discussed. A four-carbon spacer provided
      optimal activity within the two homologous series. Conformational investigations
      of the lead compound, isoindolinone 2, were conducted in an attempt to account
      for the superior activity observed for the butyl derivatives. On the basis of NMR
      and molecular modeling studies, two types of folded structures were proposed and
      several conformationally restrained analogues were synthesized. In general,
      restrictions incorporated within the linking bridge were detrimental to activity.

PMID- 8568803
TI  - High-affinity partial agonist imidazo[1,5-a]quinoxaline amides, carbamates, and
      ureas at the gamma-aminobutyric acid A/benzodiazepine receptor complex.
AB  - A series of imidazo[1,5-a]quinoxaline amides, carbamates, and ureas which have
      high affinity for the gamma-aminobutyric acid A/benzodiazepine receptor complex
      was developed. Compounds within this class have varying efficacies ranging from
      antagonists to full agonists. However, most analogs were found to be partial
      agonists as indicated by [35S]TBPS and Cl- current ratios. Many of these
      compounds were also effective in antagonizing metrazole-induced seizures in
      accordance with anticonvulsant and possible anxiolytic activity. Selected
      quinoxalines displayed limited benzodiazepine-type side effects such as ethanol
      potentiation and physical dependence in animal models. Dimethylamino urea 41
      emerged as the most interesting analog, having a partial agonist profile in vitro
      while possessing useful activity in animal models of anxiety such as the Vogel
      and Geller assays. In accordance with its partial agonist profile, 41 was devoid
      of typical benzodiazepine side effects.

PMID- 8568804
TI  - New sigma and 5-HT1A receptor ligands: omega-(tetralin-1-yl)-n-alkylamine
      derivatives.
AB  - Two series of compounds that are structurally related to benzomorphans, derived
      by structural modification of arylpiperazines with high 5-HT1A affinity and
      moderate sigma affinity, were prepared in order to increase sigma affinity and
      selectivity. All new compounds are N-substituted-omega-(1,2,3,4
      tetrahydronaphthalen-1-yl)- or -omega-(1,2-dihydronaphthalen-4-yl)-n-alkylamines
      with, in some cases, a methoxy group on the tetralin moiety. They were tested in
      radioligand binding assays on sigma ([3H]DTG and [3H]-(+)-pentazocine), D-2
      dopaminergic, 5-HT1A and 5-HT2 serotonergic, and PCP (phencyclidine) receptors. A
      first set of compounds bearing a 4-(1-substituted)piperazine moiety as terminal
      fragment on the alkyl chain showed moderate to high sigma affinity (Ki = 5.3-139
      nM), the most active and selective being 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4
      tetrahydronaphthalen-1-yl)-n- propyl ]piperazine (14), with probable pronounced
      sigma 2 affinity (Ki = 5.3 nM on [3H]DTG and Ki = 71 nM on [3H]-(+)-pentazocine).
      Moreover, compound 13, a 1-benzylpiperazine analogue of 14, preserved a dual high
      5-HT1A and sigma affinity (Ki = 3.6 nM on [3H]-5-HT and Ki = 7.0 nM on [3H]DTG).
      The second set of compounds includes some N-phenylalkyl derivatives of 3-(5
      methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)- n-propylamine that can be considered
      to be open-chain derivatives of 4-substituted-1-arylpiperazines. Among these
      compounds that had a lower activity toward sigma binding sites, a high 5-HT1A
      affinity was found for the N-(3-phenylpropyl) derivative 21 (Ki = 4.4 nM) which
      demonstrated very good selectivity.

PMID- 8568805
TI  - N-methyl-D-aspartic acid receptor agonists: resolution, absolute stereochemistry,
      and pharmacology of the enantiomers of 2-amino-2-(3-hydroxy-5-methyl-4
      isoxazolyl)acetic acid.
AB  - (R,S)-2-Amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid [(R,S)-AMAA, 4] is a
      potent and selective agonist at the N-methyl-D-aspartic acid (NMDA) subtype of
      excitatory amino acid receptors. Using the Ugi "four-component condensation"
      method, the two diastereomers (2R)- and (2S)-2-[3-(benzyloxy)-5-methyl-4
      isoxazolyl]N-tert-butyl-2- [N-[(S)-1-phenylethyl]benzamido]-acetamide (16 and 17,
      respectively) were synthesized and separated chromatographically. The absolute
      stereochemistry of 16 was confirmed by an X-ray analysis. Deprotection of these
      intermediates did, however, provide (R)- (8) and (S)- (9) AMAA, respectively, in
      extensively racemized forms. N-BOC-protected (R,S)-AMAA (21) was successfully
      resolved via diastereomeric salt formation using cinchonidine. The stereochemical
      purity and stability of 8 and 9 obtained via this resolution were determined
      using chiral HPLC. (R)-AMAA (8) showed peak affinity for [3H]AMPA receptor sites
      (IC50 = 72 +/- 13 microM) and was shown to be a more potent inhibitor of [3H]CPP
      binding (IC50 = 3.7 +/- 1.5 microM) than (S)-AMAA (9) (IC50 = 61 +/- 6.4 microM).
      Neither enantiomer of AMAA affected [3H]kainic acid receptor binding
      significantly. In electrophysiological studies using rat brain tissue, 8 (EC50 =
      7.3 +/- 0.3 microM) was 1 order of magnitude more potent than 9 (EC50 = 75 +/- 9
      microM) as an NMDA receptor agonist.

PMID- 8568806
TI  - Conformationally constrained analogues of diacylglycerol. 10. Ultrapotent protein
      kinase C ligands based on a racemic 5-disubstituted tetrahydro-2-furanone
      template.
AB  - 5,5-Bis(hydroxymethyl)tetrahydro-2-furanone and its isomer 4,4
      bis(hydroxymethyl)tetrahydro-2-furanone were investigated as possible templates
      for the construction of conformationally constrained analogues of the
      biologically important second messenger, diacylglycerol (DAG). The former lactone
      contains embedded within its structure an exact glycerol moiety, while in the
      latter the ring oxygen has been transposed to the other side of the carbonyl
      group. All target compounds were synthesized as racemates from 1,3-dihydroxy-2
      propanone. The 5,5-bis(hydroxymethyl)tetrahydro-2-furanone proved to be the
      better template for the construction of DAG surrogates that were demonstrated to
      have high binding affinities for the biological target, protein kinase C (PK-C).
      The simplest target compounds derived from this template (3e and 3f) have one of
      the hydroxyl moieties functionalized either as a myristate or as an oleate ester.
      The simplest target compound (9c) derived from the ineffective 4,4-bis
      (hydroxymethyl)tetrahydro-2-furanone template was investigated only with a
      myristoyl acyl chain. Reducing the long acyl chain to an acetyl moiety and
      attaching a compensating lipophilic chain to the lactone ring as an alpha
      alkylidene moiety produced compounds 10e and 10f (Z-isomers) and 11e and 11f (E
      isomers), which were constructed on the more effective 5,5
      bis(hydroxymethyl)tetrahydro-2-furanone template. Targets 14c (Z-isomer) and 15c
      (E-isomer) were derived, in turn, from 4,4-bis(hydroxymethyl)tetrahydro-2
      furanone. The affinities of these ligands for PK-C were assessed in terms of
      their ability to displace bound [3H-20]phorbol 12,13-dibutyrate (PDBU) from the
      single isozyme PK-C alpha. The biological data support the hypothesis that the
      increase in binding affinity for PK-C shown by some of these constrained DAG
      mimetics appears to be entropic in nature. Two of the designed ligands (10e and
      10f) showed the highest affinities (34 and 24 nM, respectively) reported so far
      for a DAG analogue. Assuming that the interaction between these racemic compounds
      and PK-C is stereospecific, the potency of the active enantiomer is anticipated
      to double.

PMID- 8568807
TI  - In vitro and in vivo studies of benzisoquinoline ligands for the brain synaptic
      vesicle monoamine transporter.
AB  - Tetrabenazine is a high-affinity inhibitor of the vesicular monoamine transporter
      in mammalian brain. As part of a program to develop in vivo imaging agents for
      these transporters in human brain, a series of 2-alkylated dihydrotetrabenazine
      ligands was synthesized and evaluated in vitro and in vivo for binding to the
      brain vesicular monoamine transporter. Additions of organometallic reagents to
      tetrabenazine produced 2-methyl, 2-ethyl, 2-n-propyl, 2-isopropyl, and 2-isobutyl
      derivatives of dihydrotetrabenazine. The stereochemistry and conformation of the
      addition products were thoroughly verified by two-dimensional NMR techniques. All
      of these alkyl derivatives displayed in vitro affinity for the vesicular
      monoamine transporter binding site in rat brain using competitive assays with the
      radioligand [3H]methoxytetrabenazine. Except for the isopropyl derivative, all
      compounds when tested at 10 mg/kg iv showed an ability to inhibit in vivo
      accumulation of the radioligand [11C]methoxytetrabenazine in the mouse brain
      striatum. Derivatives with small alkyl groups (methyl, ethyl) were more effective
      than those with large groups (propyl, isobutyl). These studies suggest that large
      groups in the 2-position of the benzisoquinoline structure will significantly
      diminish both in vitro and in vivo binding of these compounds to the vesicular
      monoamine transporter.

PMID- 8568808
TI  - Structure-activity relationships in a series of 2(1H)-quinolones bearing
      different acidic function in the 3-position: 6,7-dichloro-2(1H)-oxoquinoline-3
      phosphonic acid, a new potent and selective AMPA/kainate antagonist with
      neuroprotective properties.
AB  - Recently, we reported the synthesis of 3-(sulfonylamino)-2(1H)-quinolones, a new
      series of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate
      and N-methyl-D-aspartic acid (NMDA)/glycine antagonists. By exploring the
      structure-activity relationships (SAR) in this series, we were able to identify
      the 6,7-dinitro derivative 6 as a potent and balanced antagonist at both
      receptors. Unfortunately, compound 6 was devoid of in vivo activity in mice
      anticonvulsant testing. To overcome this critical limitation, new compounds
      bearing various acidic moieties at the 3-position of the quinolone skeleton were
      synthesized and evaluated. The SAR of these new analogues indicated that not all
      acidic groups are acceptable at the 3-position: A rank order of potency going
      from carboxylic approximately phosphonic > tetrazole > mercaptoacetic >
      hydroxamic >> other heterocyclic acids was defined. In addition, the selectivity
      between the AMPA/kainate and NMDA/glycine sites is dependent on the nature of the
      substitution (nitro > chloro for AMPA selectivity), its position (5,7- > 6,7
      pattern for glycine selectivity), and the distance between the quinolone moiety
      and the heteroatom bearing the acidic hydrogen (the longer the distance the more
      AMPA selective the compound). Among these new AMPA antagonists, we have
      identified 6,7-dichloro-2(1H)-oxoquinoline-3-phosphonic acid (24c) as a water
      soluble and selective compound endowed with an appealing pharmacological profile.
      Compared with the reference AMPA antagonist NBQX, the phosphonic acid 24c is much
      less potent in vitro but almost equipotent in vivo in the audiogenic seizures
      model after intraperitoneal administration. Moreover, unlike NBQX, compound 24c
      is also active after oral administration. In the gerbil global ischemia model,
      compound 24c shows a neuroprotective effect at 10 mg/kg/ip, equivalent to the
      reference NBQX.

PMID- 8568809
TI  - Substituted xanthines, pteridinediones, and related compounds as potential
      antiinflammatory agents. Synthesis and biological evaluation of inhibitors of
      tumor necrosis factor alpha.
AB  - A series of analogues of pentoxifylline metabolites were prepared in the purine,
      pteridine, [1,2,5]-thiadiazolo[3,4-d]pyrimidine, and quinazoline ring systems and
      evaluated for their ability to inhibit the production of tumor necrosis factor
      alpha (TNF alpha) in human peripheral blood monocytes stimulated with bacterial
      lipopolysaccharide (LPS). The more active compounds were also tested for
      inhibition of cyclic AMP phosphodiesterase type IV (PDE IV) from human
      neutrophils in order to help determine their mechanism of action. Selected
      compounds which showed good activity in the in vitro TNF alpha assay were
      evaluated in an in vivo LPS-induced leukopenia model in mice. The most potent
      compounds in the TNF alpha assay, 6, 31, and 58, inhibited TNF alpha production
      at an IC50 of approximately 5 microM for each. Compound 58 was a very poor
      inhibitor of PDE IV but was the most active at preventing the leukopenia induced
      by TNF alpha in mice, providing more than 60% protection at 50 mg/kg. Thus,
      compounds such as 58, which are good inhibitors of TNF alpha production but are
      devoid of PDE IV inhibitory properties, may have potential as new
      antiinflammatory agents.

PMID- 8568810
TI  - The squalestatins: decarboxy and 4-deoxy analogues as potent squalene synthase
      inhibitors.
AB  - Squalestatins without either the hydroxy group at C-4 or the carboxylic acid at C
      3 or C-4 were prepared and evaluated for their ability to inhibit rat liver
      microsomal squalene synthase (SQS) in vitro. These modifications were well
      tolerated for compounds with the 4,6-dimethyloctenoate ester at C-6 (S1 series).
      However in analogues without the C-6 ester (H1 series), removal of the C-4
      hydroxy group gave compounds with reduced potency, whereas decarboxylation at C-3
      resulted in a dramatic loss of SQS inhibitory activity. In comparison with S1 1,
      C-4 deoxyS1 3 and C-3 decarboxyS1 10 have shorter in vivo durations of action on
      the inhibition of hepatic cholesterol biosynthesis in rats. C-4 deoxyS1 3 retains
      good serum cholesterol-lowering ability in marmosets, while C-3 decarboxyS1 10
      showed only a marginal effect even at high dose.

PMID- 8568811
TI  - Design and synthesis of non-peptide Ras CAAX mimetics as potent
      farnesyltransferase inhibitors.
AB  - Cysteine farnesylation of the ras oncogene product Ras is required for its
      transforming activity and is catalyzed by farnesyltransferase (FTase). The Ras
      carboxyl terminal tetrapeptide CAAX (C is cysteine, A is any aliphatic amino
      acid, X is methionine or serine) is the minimum sequence for FTase recognition.
      We report here the design, synthesis, and biological characterization of Ras CAAX
      non-peptide mimetics in which the cysteine is linked through a reduced
      pseudopeptide bond to 4-amino-3'-carboxybiphenyl. These non-peptide mimetics are
      potent inhibitors of FTase (IC50 = 40 nM for the most potent inhibitor) and are
      highly selective for FTase over GGTase I (geranylgeranyltransferase I). They are
      not substrates for farnesylation, do not have peptidic features, and have no
      hydrolyzable bonds. Structure-activity studies reveal the importance of the
      position of the carboxylic acid on the aryl ring as well as the reduction of the
      cysteine amide bond. Substitution at the 2-position of 4-amino-3'-carboxybiphenyl
      increases inhibitory potency, while the removal of the carboxylic acid results in
      a 10-fold loss of inhibitory activity.

PMID- 8568813
TI  - Azole phenoxy hydroxyureas as selective and orally active inhibitors of 5
      lipoxygenase.
AB  - Azole phenoxy hydroxyureas are a new class of 5-lipoxygenase (5-LO) inhibitors.
      Structure-activity relationship studies have demonstrated that electronegative
      substituents on the 2-phenyl portion of the oxazole tail increased the ex vivo
      potency of these inhibitors. Similar substitutions on the thiazole analogs had
      only minor contribution to the ex vivo activity. The trifluoromethyl-substituted
      oxazole 24 was the best compound of the oxazole series in both the ex vivo (6 h
      pretreated rats) and in vivo (3 h pretreated rats) RPAR assay with ED50 values of
      approximately 1 and 3.6 mg/kg, respectively, but was weakly active in the
      allergic guinea pig assay. Oxazole 50 was equally active in both the RPAR and
      guinea pig in vivo models and was similar to zileuton. The unsubstituted thiazole
      52 was the best compound of the thiazole series, by inhibiting the leukotriene B4
      biosynthesis in the RPAR assay (3 h pretreated rats) by 99%, at an oral dose of
      10 mg/kg, and the bronchoconstriction in the allergic guinea pig by 50%, at an
      intravenous dose of 10 mg/kg. Oxazole 24 demonstrated high and selective 5-LO
      inhibitory activity in the in vitro assays, with IC50 values ranging from 0.08
      microM in mouse macrophages to 0.8 microM in human peripheral monocytes to 1.2
      microM in human whole blood. This activity was selective for 5-LO, as
      concentrations up to 15 microM in mouse macrophages did not affect prostaglandin
      formation. Oxazole 59 was the most active inhibitor in the human monocyte assay
      with an IC50 value of 7 nM.

PMID- 8568812
TI  - Development of highly potent inhibitors of Ras farnesyltransferase possessing
      cellular and in vivo activity.
AB  - Analogs of CVFM (a known nonsubstrate farnesyltransferase (FT) inhibitor derived
      from a CA1A2X sequence where C is cysteine, A is an aliphatic residue, and X is
      any residue) were prepared where phenylalanine was replaced by (Z)
      dehydrophenylalanine, 2-aminoindan-2-carboxylate, 1,2,3,4-tetrahydroisoquinoline
      3-carboxylate (Tic), and indoline-2-carboxylate. The greatest improvement in FT
      inhibitory potency was observed for the Tic derivative (IC50 = 1 nM); however,
      this compound was ineffective in blocking oncogenic Ras-induced transformation of
      NIH-3T3 fibroblast cells. A compound was prepared in which both the Cys-Val
      methyleneamine isostere and the Tic replacement were incorporated. This
      derivative inhibited FT with an IC50 of 0.6 nM and inhibited anchorage
      independent growth of stably transformed NIH-3T3 fibroblast cells by 50% at 5
      microM. Replacing the A1 side chain of this derivative with a tert-butyl group
      and replacing the X position with glutamine led to a derivative with an IC50 of
      2.8 nM and an EC50 of 0.19 microM, a 26-fold improvement over (S*,R*)-N-[[2-[N-(2
      amino-3-mercaptopropyl)-L-valyl]-1,2,3,4- tetrahydro-3-isoquinolinyl]carbonyl]-L
      methionine. This derivative, (S*,R*)-N-[[2-[N-(2-amino-3-mercaptopropyl)-L-tert
      leucyl]-1,2,3,4 - tetrahydro-3-isoquinolinyl]-carbonyl]-L-glutamine, was
      evaluated in vivo along with (S*,R*)-N-[[2-[N-(2-amino-3- mercaptopropyl)-L-tert
      leucyl]-1,2,3,4-tetrahydro-3- isoquinolinyl]carbonyl]-L-methionine methyl ester
      for antitumor activity in an athymic mouse model implanted ip with H-ras
      transformed rat-1 tumor cells. When administered by injection twice a day at 45
      mg/kg for 11 consecutive days, both compounds showed prolonged survival time (T/C
      = 142-145%), thus demonstrating efficacy against ras oncogene-containing tumors
      in vivo.

PMID- 8568814
TI  - Dibenzoxepinone hydroxylamines and hydroxamic acids: dual inhibitors of
      cyclooxygenase and 5-lipoxygenase with potent topical antiinflammatory activity.
AB  - Hydroxylamine and hydroxamic acid derivatives of a known nonsteroidal
      antiinflammatory dibenzoxepine series display both cyclooxygenase (CO) and 5
      lipoxygenase (5-LO) inhibitory properties. Many of these new dual CO/5-LO
      inhibitors also exhibit potent topical antiinflammatory activity in the
      arachidonic acid-induced murine ear edema model. On the basis of their promising
      profile of in vitro and in vivo activities, hydroxamic acids 24h, 3-(6,11-dihydro
      11-oxodibenz[b,e]oxepin-2-yl)-N-hydroxy-N-++ +methylpropanamide (HP 977), and 25,
      3-(6,11-dihydrodibenz[b,e]oxepin-2-yl)-N-hydroxy-N- methylpropanamide (P10294),
      were selected as developmental candidates for the topical treatment of
      inflammatory skin disorders.

PMID- 8568816
TI  - Tyrosine kinase inhibitors. 8. An unusually steep structure-activity relationship
      for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a
      potent inhibitor of the epidermal growth factor receptor.
AB  - 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (32, PD 153035) is a very potent
      inhibitor (IC50 0.025 nM) of the tyrosine kinase activity of the epidermal growth
      factor receptor (EGFR), binding competitively at the ATP site. Structure-activity
      relationships for close analogues of 32 are very steep. Some derivatives have
      IC50s up to 80-fold better than predicted from simple additive binding energy
      arguments, yet analogues possessing combinations of similar phenyl and
      quinazoline substituents do not show this "supra-additive" effect. Because some
      substituents which are mildly deactivating by themselves can be strongly
      activating when used in the correct combinations, it is proposed that certain
      substituted analogues possess the ability to induce a change in the conformation
      of the receptor when they bind. There is some bulk tolerance for substitution in
      the 6- and 7-positions of the quinazoline, so that 32 is not the optimal
      inhibitor for the induced conformation. The diethoxy derivative 56 [4-(3
      bromoanilino)-6,7-diethoxyquinazoline] shows an IC50 of 0.006 nM, making it the
      most potent inhibitor of the tyrosine kinase activity of the EGFR yet reported.

PMID- 8568815
TI  - Diarylspiro[2.4]heptenes as orally active, highly selective cyclooxygenase-2
      inhibitors: synthesis and structure-activity relationships.
AB  - A novel series of 5,6-diarylspiro[2.4]hept-5-enes was shown to provide highly
      potent and selective cyclooxygenase-2 (COX-2) inhibitors. A study of structure
      activity relationships in this series suggests that 3,4-disubstituted phenyl
      analogs are generally more selective than 4-substituted phenyl analogs and that
      replacement of the methyl sulfone group on the 6-phenyl ring with a sulfonamide
      moiety results in compounds with superior in vivo pharmacological properties,
      although with lower COX-2 selectivity. Several compounds have been shown to
      possess promising pharmacological properties in adjuvant-induced arthritis and
      edema analgesia models. The absence of gastrointestinal (GI) toxicity at 200 mpk
      of several selected compounds in rats and mice corresponds well with the weak
      potency for inhibition of COX-1 observed in the enzyme assay. Methyl sulfone 55
      and sulfonamide 24 were shown to have superior in vivo pharmacological profiles,
      low GI toxicity, and good oral bioavailability and duration of action.

PMID- 8568817
TI  - Theoretical study of inhibition of adenosine deaminase by (8R)-coformycin and
      (8R)-deoxycoformycin.
AB  - Molecular dynamics and free energy simulations were performed to examine the
      binding of (8R)-deoxycoformycin and (8R)-coformycin to adenosine deaminase. The
      two inhibitors differ only at the 2' position of the sugar ring; the sugar moiety
      of conformycin is ribose, while it is deoxyribose for deoxycoformycin. The 100 ps
      molecular dynamics trajectories reveal that Asp 19 and His 17 interact strongly
      with the 5' hydroxyl group of the sugar moiety of both inhibitors and appear to
      play an important role in binding the sugar. The 2' and 3' groups of the sugars
      are near the protein-water interface and can be stabilized by either protein
      residues or water. The flexibility of the residues at the opening of the active
      site helps to explain the modest difference in binding of the two inhibitors and
      how substrates/inhibitors can enter an otherwise inaccessible binding site.

PMID- 8568818
TI  - Conformational analysis of D1 dopamine receptor agonists: pharmacophore
      assessment and receptor mapping.
AB  - Compute-aided conformational analysis was used to characterize the agonist
      pharmacophore for D1 dopamine receptor recognition and activation. Dihydrexidine
      (DHX), a high-affinity full agonist with limited conformational flexibility,
      served as a structural template that aided in determining a molecular geometry
      that would be common for other more flexible, biologically active agonists. The
      intrinsic activity of the drugs at D1 receptors was assessed by their ability to
      stimulate adenylate cyclase activity in rat striatal homogenates (the accepted
      measure of D1 receptor activation). In addition, affinity data on 12 agonists
      including six purported full agonists (dopamine, dihydrexidine, SKF89626,
      SKF82958, A70108, and A77636), as well as six less efficacious structural
      analogs, were obtained from D1 dopamine radioreceptor-binding assays. The active
      analog approach to pharmacophore building was applied as implemented in the SYBYL
      software package. Conformational analysis and molecular mechanics calculations
      were used to determine the lowest energy conformation of the active analogs
      (i.e., full agonists), as well as the conformations of each compound that
      displayed a common pharmacophoric geometry. It is hypothesized that DHX and other
      full agonists may share a D1 pharmacophore made up of two hydroxy groups, the
      nitrogen atom (ca. 7 A from the oxygen of m-hydroxyl) and the accessory ring
      system characterized by the angle between its plane and that of the catechol ring
      (except for dopamine and A77636). For all full agonists (DHX, SKF89626, SKF82958,
      A70108, A77636, and dopamine), the energy difference between the lowest energy
      conformer and those that displayed a common pharmacophore geometry was relatively
      small (< 5 kcal/mol). The pharmacophoric conformations of the full agonists were
      also used to infer the shape of the receptor binding site. Based on the union of
      the van der Waals density maps of the active analogs, the excluded receptor
      volume was calculated. Various inactive analogs (partial agonists with D1 K0.5 >
      300 nM) subsequently were used to define the receptor essential volume (i.e.,
      sterically intolerable receptor regions). These volumes, together with the
      pharmacophore results, were integrated into a three-dimensional model estimating
      the D1 receptor active site topography.

PMID- 8568819
TI  - Conformationally constrained analogues of diacylglycerol. 11. Ultrapotent protein
      kinase C ligands based on a chiral 5-disubstituted tetrahydro-2-furanone
      template.
AB  - Conformationally constrained analogues of diacylglycerol (DAG) built on a racemic
      5(-)[(acyloxy)-methyl]-5-(hydroxymethyl)tetrahydro-2-furanone template were shown
      previously to have excellent binding affinities for protein kinase C (PK-C).
      Since the interaction of PK-C with DAG is stereospecific, it was anticipated that
      PK-C would bind tightly to only one enantiomeric form of the compounds
      constructed with this new lactone template. Separation of enantiomers by chiral
      HPLC was discarded due to the ease with which acyl migration occurs in these
      class of compounds, and a total chiral synthesis was undertaken. Prior to
      chemical synthesis, the selection of the "correct" enantiomeric template was
      predicted by a molecular conformational analysis that compared the two
      enantiomers of DAG in their presumed "active" conformation with the two
      enantiomeric lactone templates. This presumed "active" conformation for DAG was
      derived from a previously developed pharmacophore model that uses the molecule of
      a potent phorbol diester as the ideal rigid template. The results from this
      analysis indicated that the "correct" lactone template corresponded to the
      inactive (R)-isomer of DAG. This analysis also predicted that the lactone
      template corresponding to the active (S)-DAG enantiomer would not fit adequately
      into the pharmacophore. The chiral syntheses of target compounds 2, 4, and 6,
      constructed on the selected, and presumably "correct" lactone template, were
      achieved from a common bicyclic intermediate (5R,8R,9R)-8,9-O-isopropylidene-2
      keto-1,7-dioxaspiro[4.4]nonane (10) that was synthesized from commercially
      available 1,2:3,5-di-O-isopropylidene-alpha-D-threo-apiofuranose (7) by a very
      effective spirolactonization approach. On the basis of their ability to inhibit
      the binding of [3H-20]phorbol 12,13-dibutyrate (PDBU) to PK-C alpha, the
      enantiomeric ligands 2, 4, and 6 were twice as potent as the corresponding
      racemates. These results confirm that binding of these lactones is stereospecific
      and consistent with a binding mechanism similar to that of DAG.

PMID- 8568820
TI  - Studies of cardiotonic agents. 8. Synthesis and biological activities of
      optically active 6-(4-(benzylamino)-7-quinazolinyl)-4,5-dihydro-5-methyl-3(2H)-
      pyridazinone (KF15232).
AB  - We previously reported that (+/-)-6-(4-(benzylamino)-7-quinazolinyl)-4,5- dihydro
      5-methyl-3(2H)-pyridazinone (+/-)-1, KF15232) showed potent cardiotonic activity
      with a strong myofibrillar Ca(2+)-sensitizing effect. As an extension of our
      work, we attempted to synthesize optically active 1. (+/-)-4-(4-(Benzylamino)-7
      quinazolinyl)-3-methyl-4-oxobutyric acid (-)-menthyl ester (6) was separated into
      both diastereoisomers, and each was converted to optically pure 1 (> 99% ee) in
      an enantioselective manner. In order to determine the absolute configuration of
      the isomers, an alternative synthesis of optically active 1 was employed. The
      precursor of (-)-1 ((+)-9) was obtained by enantioselective synthesis from (R)-D
      alanine. Consequently, we concluded that the absolute configuration of (-)-1 at
      the 5-position of the pyridazinone ring was R. The cardiotonic effects and
      inhibitory activities to PDE III and V of racemic 1 and (-)-1 were more potent
      than those of (+)-1. These compounds also demonstrated greater vasorelaxant
      effects in guinea pig aorta. In contrast, (+)-1 showed only weak cardiotonic and
      vasodilating effects, although the compound displayed potent Ca(2+)-sensitizing
      activity. Racemic and (-)-1 attracted our interest for the treatment of
      congestive heart failure.

PMID- 8568821
TI  - Cardioselective antiischemic ATP-sensitive potassium channel openers. 4.
      Structure-activity studies on benzopyranylcyanoguanidines: replacement of the
      benzopyran portion.
AB  - The results of our efforts aimed at the replacement of the benzopyran ring of the
      lead cardiac selective antiischemic ATP-sensitive potassium channel (KATP) opener
      (4) are described. Systematic modification of the benzopyran ring of 4 resulted
      in the discovery of a structurally simpler acyclic analog (8) with slightly lower
      antiischemic potency than the lead compound 4. Further structure-activity studies
      on the acyclic analog 8 provided the 2-phenoxy-3-pyridylurea analog 18 with
      improved antiischemic potency and selectivity compared to the benzopyran-based
      compound 4. These data demonstrate that the benzopyran ring of 4 and its
      congeners is not mandatory for antiischemic activity and cardiac selectivity. The
      results described in this paper also show that, as for the benzopyran class of
      compounds, the structure-activity relationships for the antiischemic and
      vasorelaxant activities of KATP openers are distinct. The mechanism of action of
      the acyclic analogs (e.g., 18) still appears to involve KATP opening as their
      cardioprotective effects are abolished by pretreatment with the KATP blocker
      glyburide.

PMID- 8568822
TI  - Binding of O-alkyl derivatives of serotonin at human 5-HT1D beta receptors.
AB  - In humans, 5-HT1D serotonin receptors represent terminal autoreceptors, and there
      is some evidence that 5-HT1D ligands may be useful in the treatment of migraine.
      The most widely used 5-HT1D agonist is sumatriptan; however, this agent
      reportedly displays little selectivity for 5-HT1D versus 5-HT1A receptors. To
      identify novel serotonergic agents with enhanced 5-HT1D versus 5-HT1A
      selectivity, we attempted to take advantage of possible differences in the
      regions of bulk tolerance associated with the 5-position of the 5-HT binding
      sites for these two populations of receptors. Examination of a series of 5
      (alkyloxy)tryptamine derivatives demonstrated that compounds with unbranched
      alkyl groups of up to eight carbon atoms bind with high affinity at human 5-HT1D
      beta receptors (Ki < 5 nM) but demonstrate less than 50-fold selectivity relative
      to 5-HT1A receptors. Alkyl groups longer than eight carbon atoms impart reduced
      affinity for 5-HT1A receptors whereas groups longer than nine carbon atoms lead
      to compounds with reduced affinity at 5-HT1D beta receptors. 5
      (Nonyloxy)tryptamine (10) represents a compound with optimal 5-HT1D beta affinity
      (Ki = 1 nM) and selectivity (> 300-fold). Branching of the alkyl chain, to 5
      [(7,7-dimethylheptyl)oxy]tryptamine (15), results in an agent with somewhat lower
      affinity (5-HT1D beta Ki = 2.3 nM) but with greater (i.e, 400-fold) 5-HT1D versus
      5-HT1A selectivity. Replacement of the oxygen atom of 10 with a methylene group
      (i.e., 20), replacement of the O-proximate methylene with a carbonyl group (i.e.,
      ester 26), or cyclization of the aminoethyl moiety to a carbazole (e.g., 34, 36)
      or beta-carboline (i.e., 37), result in reduced affinity and/or selectivity. None
      of the compounds examined displayed significant selectivity for 5-HT1D beta
      versus 5-HT1D alpha sites; nevertheless, compounds 10 (recently shown to have as
      a 5-HT1D agonist) and 15 represent the most 5-HT1D versus 5-HT1A selective agents
      reported to date.

PMID- 8568823
TI  - Nonpeptide angiotensin II receptor antagonists: synthesis, biological activities,
      and structure-activity relationships of imidazole-5-carboxylic acids bearing
      alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related
      compounds.
AB  - A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl
      substituents at the 4-position and their related compounds were prepared and
      evaluated for their antagonistic activities to the angiotensin II (AII) receptor.
      Among them, the 4-(1-hydroxyalkyl)-imidazole derivatives had strong binding
      affinity to the AII receptor and potently inhibited the AII-induced pressor
      response by intravenous administration. Various esters of these acids showed
      potent and long-lasting antagonistic activity by oral administration. The most
      promising compounds were (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (CS-866) and
      (pivaloyloxy)-methyl esters of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2'-1H
      tetrazol-5- ylbiphenyl-4-yl)-methyl]imidazole-5-carboxylic acid (26c). A study
      involving stereochemical comparison of 26c with the acetylated C-terminal
      pentapeptide of AII was also undertaken.

PMID- 8568824
TI  - Synthesis and antitumor evaluation of a highly potent cytotoxic DNA cross-linking
      polyamine analogue, 1,12-diaziridinyl-4,9-diazadodecane.
AB  - A diaziridinylspermine analogue, 1,12-diaziridinyl-4,9-diazadodecane (NSC
      667005), was synthesized as a bisalkylating agent with a polyamine backbone. DNA
      cross-linking was detected in the reaction of linearized pBR322 DNA with 1,12
      diaziridinyl-4,9-diazadodecane at concentrations comparable with that required
      for cross-linking by two nitrogen mustard drugs, mechlorethamine and melphalan. A
      significant increase in life span of female CD2F1 mice bearing L1210 murine
      leukemia was observed after intravenous administration of 1,12-diaziridinyl-4,9
      diazadodecane in doses of less than 2.7 mg/kg, given on days 1, 5, and 9 of
      treatment.

PMID- 8568825
TI  - Conformationally constrained analogues of diacylglycerol. 12. Ultrapotent protein
      kinase C ligands based on a chiral 4,4-disubstituted heptono-1,4-lactone
      template.
AB  - Conformationally constrained analogues of diacylglycerol (DAG) built on a 5(
      )[(acyloxy)methyl]-5-(hydroxymethyl)tetrahydro-2-furanone template (1, Chart 1)
      were shown previously to bind tightly to protein kinase C alpha (PK-C alpha) in a
      stereospecific manner. These compounds, however, racemized readily through rapid
      acyl migration and lost biological potency. In order to circumvent this problem,
      the "reversed ester" analogues were designed as a new set of PK-C ligands. This
      reversal of the ester function produced some new DAG mimetics that are embedded
      in a C-4 doubly-branched heptono-1,4-lactone template. The reversed ester
      analogues were impervious to racemization, and their chemically distinct branches
      facilitated the enantiospecific syntheses of all targets. Compound 2, the
      simplest reversed ester analogue of 1 (Chart 1), exhibited a 3.5-fold reduction
      in binding affinity toward PK-C alpha which we attributed to the loss of a
      stabilizing gauche interaction that caused the ester branch in 2 to be more
      disordered than in the normal ester 1. However, conversion of the propanoyl
      branch of 2 into a propenoyl branch restored binding affinity (3 versus 5). As
      expected, the compounds bound to the enzyme with strict enantioselectivity (3 and
      5 versus 4 and 6). Functionalization of the propenoyl-branched compounds as alpha
      alkylidene lactones, in a manner which proved successful with the 5(
      )[(acyloxy)methyl]-5-(hydroxymethyl)tetrahydro-2-furanone template (9 and 10),
      produced stable compounds with equivalent ultrapotent binding affinities for PK-C
      alpha (7 and 8). The additional incorporation of the propenoyl-branched carbonyl
      into a gamma-lactone ring was performed (11-14) not only to derive a possible
      additional entropic advantage but also to confirm the spatial disposition of this
      carbonyl function in the ligand-enzyme complex. Although no additional entropic
      advantage was derived, the high binding affinities displayed by compounds 11 and
      12 helped to establish the correct orientation of the equivalent carbonyl group
      in PK-C-bound DAG. As expected, these DAG analogues activated PK-C alpha. The
      most potent agonist, compound 8, stimulated phosphorylation of the alpha
      pseudosubstrate peptide, and in primary mouse keratinocytes it caused inhibition
      of binding of epidermal growth factor with an ED50 of approximately 1 microM. In
      contrast to the phorbol esters, compound 8 did not induce acute edema or
      hyperplasia in skin of CD-1 mice, and its pattern of downregulation with several
      PK-C isozymes was different from that of phorbol 12-myristate 13-acetate (PMA).

PMID- 8568826
TI  - Synthesis and modeling studies with monocyclic analogues of mycophenolic acid.
AB  - Two stepwise procedures, developed for the introduction of the (E)-4-methyl-4
      hexenoic acid side chain of mycophenolic acid, were used in the synthesis of
      monocyclic mycophenolic acid analogues 2a-i. The derivatives with a methyl group
      or hydrogen at C-4 and lacking the lactone moiety were much less cytotoxic than
      mycophenolic acid. The monocyclic analogues with a C-4 chloro group did show some
      activity, albeit much less than mycophenolic acid. The observed differences in
      potency are rationalized by semiempirical calculations of intramolecular H-bonds.

PMID- 8568827
TI  - Synthesis and biological activity of folic acid and methotrexate analogues
      containing L-threo-(2S,4S)-4-fluoroglutamic acid and DL-3,3-difluoroglutamic
      acid.
AB  - The stereospecific syntheses of L-threo-gamma-fluoromethotrexate (1t) and L-threo
      gamma-fluorofolic acid (3t) are reported. Compounds 1t and 3t have no substrate
      activity with folylpoly-gamma-glutamate synthetase isolated from CCRF-CEM human
      leukemia cells, and compound 1t inhibits human dihydrofolate reductase at similar
      levels as methotrexate. The synthesis of DL-3,3-difluoroglutamic acid (6) and its
      incorporation into DL-beta,beta-difluorofolic acid (4) are also reported.
      Compound 4 acts as a better substrate for human CCRF-CEM folylpoly-gamma
      glutamate synthetase than folic acid (V/K = ca. 7-fold greater). Thus,
      replacement of the glutamate moiety of methotrexate and folic acid with 4
      fluoroglutamic acid and 3,3-difluoroglutamic acid results in folates and
      antifolates with altered polyglutamylation activity.

PMID- 8568828
TI  - Synthesis and biological evaluation of DL-4,4-difluoroglutamic acid and DL
      gamma,gamma-difluoromethotrexate.
AB  - DL-4,4-Difluoroglutamic acid (DL-4,4-F2Glu) and its methotrexate analogue, DL
      gamma,gamma-difluoromethotrexate (DL-gamma,gamma-F2MTX), were synthesized and
      evaluated as alternate substrates or inhibitors of folate-dependent enzymes.
      Synthesis of DL-4,4-F2Glu involved the nitroaldol reaction of ethyl nitroacetate
      with a difluorinated aldehyde ethyl hemiacetal as a key step. Attempted ligation
      of DL-4,4-F2Glu to methotrexate (MTX), catalyzed by human folylpoly-gamma
      glutamate synthetase (FPGS), revealed that DL-4,4-F2Glu is a poor alternate
      substrate. DL-gamma,gamma-F2MTX was synthesized by a route proceeding through N
      [4-(methylamino)benzoyl]-4,4-difluoroglutamic acid di-tert-butyl ester followed
      by alkylation with 6-(bromomethyl)-2,4-pteridinediamine hydrobromide. DL
      gamma,gamma-F2MTX was found to be neither a substrate nor an inhibitor of human
      FPGS. The fluorinated analogue of MTX, however, inhibits DHFR and cell growth
      with the same potency as MTX.

PMID- 8568829
TI  - Quinazoline antifolate thymidylate synthase inhibitors: gamma-linked L-D, D-D,
      and D-L dipeptide analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic
      acid (ICI 198583).
AB  - The syntheses of gamma-linked L-D, D-D, and D-L dipeptide analogues of 2-desamino
      2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) are described. The
      general methodology for the synthesis of these molecules involved the preparation
      of the dipeptide derivatives employing solution phase peptide synthesis followed
      by condensation of the dipeptide free bases with the appropriate pteroic acid
      analogue via diethyl cyanophosphoridate (DEPC) activation. In the final step,
      tert-butyl esters were removed by trifluoroacetic acid (TFA) hydrolysis. Z-L-Glu
      OBut-gamma-D-Ala-OBut, for example, was prepared from alpha-tert-butyl N
      (benzyloxycarbonyl)-L-glutamate and tert-butyl D-alaninate via isobutyl-mixed
      anhydride coupling. The Z-group was removed by catalytic hydrogenolysis and the
      resulting dipeptide free base condensed with 2-desamino-2-methyl-N10-propargyl
      5,8-dideazapteroic acid via DEPC coupling. Finally, tert-butyl esters were
      removed by TFA hydrolysis to give ICI 198583-gamma-D-Ala. The compounds were
      tested as inhibitors of thymidylate synthase and L1210 cell growth. Good enzyme
      and growth inhibitory activity were found with gamma-linked L-D dipeptides, the
      best examples being the Glu-gamma-D-Glu derivative 35 (Ki = 0.19 nM, L1210 IC50 =
      0.20 +/- 0.017 microM) and the Glu-gamma-D-alpha-aminoadipate derivative 39 (Ki =
      0.12 nM, L1210 IC50 = 0.13 +/- 0.063 microM). In addition, ICI 198583 L-gamma-D
      linked dipeptides were resistant to enzymatic degradation in mice.

PMID- 8568830
TI  - (-)-Arctigenin as a lead structure for inhibitors of human immunodeficiency virus
      type-1 integrase.
AB  - The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin (2), an
      inhibitor of human immunodeficiency virus type-1 (HIV-1) replication in infected
      human cell systems, was found to suppress the integration of proviral DNA into
      the cellular DNA genome. In the present study 2 was tested with purified HIV-1
      integrase and found to be inactive in the cleavage (3'-processing) and
      integration (strand transfer) assays. However, the semisynthetic 3-O-demethylated
      congener 9 characterized by a catechol substructure exhibited remarkable
      activities in both assays. Structure-activity relationship studies with 30
      natural (1-6), semisynthetic (7-21), and synthetic (37-43, 45, 46) lignans
      revealed that (1) the lactone moiety is crucial since compounds with a butane-1,4
      diol or tetrahydrofuran substructure and also lignanamide analogues lacked
      activity and (2) the number and arrangement of phenolic hydroxyl groups is
      important for the activity of lignanolides. The congener with two catechol
      substructures (7) was found to be the most active compound in this study. 7 was
      also a potent inhibitor of the "disintegration" reaction which models the
      reversal of the strand transfer reaction. The inhibitory activity of 7 with the
      core enzyme fragment consisting of amino acids 50-212 suggests that the binding
      site of 7 resides in the catalytic domain.

PMID- 8568831
TI  - Potent human immunodeficiency virus type 1 protease inhibitors that utilize
      noncoded D-amino acids as P2/P3 ligands.
AB  - Noncoded D-amino acids have been designed to replace the quinaldic amide
      asparaginyl moiety (P2/P3 ligand) found in several potent human immunodeficiency
      virus (HIV) protease inhibitors such as LY289612. The substituted nitrogen,
      optimally an N-methanesulfonyl moiety, served as a CH2CONH2 (asparagine side
      chain mimic), while the amino acid side chain became the backbone and P3 ligand
      of these novel inhibitors. Compounds derived from S-aryl-D-cysteine proved to be
      potent HIV protease inhibitors which also exhibited potent whole cell antiviral
      activity. Oxidation of the cysteines to the sulfoxide or sulfone oxidation states
      resulted in significant improvements in potency. For example, the compound
      derived from N-(methyl-sulfonyl)-2-S-naphthylcysteine sulfone, 17c, was a 3.5 nM
      inhibitor of HIV protease which inhibited the spread of virus in MT4 cells with
      an IC50 = 4.3 nM. Compounds 17c,g,i were found to be orally bioavailable in a rat
      model.

PMID- 8568832
TI  - Stereoselective sulfoxidation of the pesticide methiocarb by flavin-containing
      monooxygenase and cytochrome P450-dependent monooxygenases of rat liver
      microsomes. Anticholinesterase activity of the two sulfoxide enantiomers.
AB  - Evidence based on thermal lability and enzyme inhibition data suggests that the
      sulfoxidation of methiocarb (an N-methylcarbamate insecticide) by rat liver
      microsomes is catalyzed by flavin-containing monooxygenase(s) (FMO) and by
      cytochrome(s) P450 (P450). In control rats, the relative proportion is ca. 50%
      P450:50% FMO. Stereoselective formation of methiocarb sulfoxide from the
      corresponding sulfide has also been examined to compare the enantioselectivity of
      the two different enzyme systems. Only the FMO-dependent sulfoxidation presents a
      high stereoselectivity with an enantiomeric excess of 88% in favor of the (A)
      enantiomer. Pretreatment of rats with different P450 inducers such as
      phenobarbital, 3-methylcholanthrene, dexamethasone, and pyrazole did not affect,
      or decreased, the rate of methiocarb sulfoxidation. Stereoselectivity of the
      reaction was modified, mainly because of changes in the relative involvement of
      FMO and P450 in sulfoxidase activity in pretreated animals. The
      acetylcholinesterase inhibition properties of methiocarb and its main metabolites
      were also investigated. Racemic methiocarb sulfoxide was slightly less inhibitory
      (Ki = 0.216 microM-1.min-1) than methiocarb, but a 10-fold difference was
      observed between the bimolecular rate constants found for the two sulfoxides
      produced (0.054 and 0.502 microM-1.min-1 for the (A) and (B) enantiomers,
      respectively).

PMID- 8568833
TI  - The anticarcinogen 3,3'-diindolylmethane is an inhibitor of cytochrome P-450.
AB  - Dietary indole-3-carbinol inhibits carcinogenesis in rodents and trout. Several
      mechanisms of inhibition may exist. We reported previously that 3,3'
      diindolylmethane, an in vivo derivative of indole-3-carbinol, is a potent
      noncompetitive inhibitor of trout cytochrome P450 (CYP) 1A-dependent
      ethoxyresorufin O-deethylase with Ki values in the low micromolar range. We now
      report a similar potent inhibition by 3,3'-diindolylmethane of rat and human
      CYP1A1, human CYP1A2, and rat CYP2B1 using various CYP-specific or preferential
      activity assays. 3,3'-Diindolylmethane also inhibited in vitro CYP-mediated
      metabolism of the ubiquitous food contaminant and potent hepatocarcinogen,
      aflatoxin B1. There was no inhibition of cytochrome c reductase. In addition, we
      found 3,3'-diindolylmethane to be a substrate for rat hepatic microsomal
      monooxygenase(s) and tentatively identified a monohydroxylated metabolite. These
      observations indicate that 3,3'-diindolylmethane can inhibit the catalytic
      activities of a range of CYP isoforms from lower and higher vertebrates in vitro.
      This broadly based inhibition of CYP-mediated activation of procarcinogens may be
      an indole-3-carbinol anticarcinogenic mechanism applicable to all species,
      including humans.

PMID- 8568834
TI  - Mechanism of antifibrotic effect of taurine and niacin in the multidose bleomycin
      hamster model of lung fibrosis: inhibition of lysyl oxidase and collagenase.
AB  - In the multiple-dose bleomycin-hamster model of pulmonary fibrosis, combined
      treatment with taurine and niacin blocks the increase in lung collagen
      deposition. We investigated the effects of taurine and niacin on lung lysyl
      oxidase and type I collagenase activities in this model. Hamsters were
      intratracheally instilled with three weekly doses of saline or bleomycin sulfate.
      Animals were fed either a diet containing 2.5% niacin and 2.5% taurine, or a
      control diet throughout the experiment. The four groups were saline-instilled
      with the control diet (BCD), bleomycin-instilled with the diet containing taurine
      and niacin (BTN), and saline-instilled with the diet containing taurine and
      niacin (STN). Animals were sacrificed at 1, 4, and 8 weeks after the last
      bleomycin instillation. Hydroxyproline per lung in the BCD group was
      significantly elevated by 38, 56, and 60% over the SCD group at 1, 4, and 8
      weeks, respectively. Lysyl oxidase activity per lung in the BCD group was
      significantly elevated by 57.5 and 91.4% over the SCD controls at 1 and 4 week
      time periods, respectively. Type I collagenase activity per lung in the BCD group
      was significantly elevated by 65 and 80% over the SCD controls at 1 and 4 weeks,
      respectively. The combined treatment with taurine and niacin abolished the
      bleomycin-induced increases in the lung hydroxyproline content and lysyl oxidase
      and collagenase activities. It was postulated that one of the mechanisms for the
      antifibrotic effect of taurine and niacin may be the blockage of bleomycin
      induced increases in the lung lysyl oxidase and collagenase activities.

PMID- 8568835
TI  - Organophosphorus inhibition and heat inactivation kinetics of particulate and
      soluble forms of peripheral nerve neuropathy target esterase.
AB  - Neuropathy target esterase (NTE) is the proposed target site for the mechanism of
      initiation of the so-called organophosphorus-induced delayed polyneuropathy
      (OPIDP). NTE is operationally defined in this article as the phenylvalerate
      esterase activity which is resistant to inhibition by 40 microM paraoxon and
      sensitive to 250 microM mipafox. Soluble (S-NTE) and particulate (P-NTE) forms of
      NTE had first been identified in hen sciatic nerve [E. Vilanova, J. Barril, V.
      Carrera, and M. C. Pellin (1990). J. Neurochem., 55, 1258-1265]. P-NTE and S-NTE
      showed different sensitivities to the inhibition by several organophosphorus
      compounds over a range of inhibitor concentrations for a 30 or 120 minute fixed
      inhibition time at 37 degrees C. S-NTE was less sensitive to the inhibition by
      O,O'-diisopropyl phosphorofluoridate (DFP), hexyl 2,5-dichlorophenyl
      phosphoramidate (H-DCP), and mipafox than P-NTE and brain NTE, while the opposite
      was true for O,S-dimethyl phosphoroamidothioate (methamidophos). For each of the
      four inhibitors assayed, S-NTE showed two components of different sensitivity
      according to the inhibition curves fitted with exponential models. However, the
      inhibition of P-NTE by mipafox, DFP, and HDCP did not show the presence of a
      considerable proportion of a second component. The kinetics of heat inactivation
      showed that P-NTE inactivated faster and to a greater extent than S-NTE. It is
      concluded that (1) sciatic nerve S-NTE is more different from brain NTE than P
      NTE; (2) P-NTE and S-NTE have different sensitivities to the inhibition by the
      studied organophosphorous compounds; (3) the inhibition curves suggest that S-NTE
      has two different enzymatic components while these are not so evident for P-NTE.

PMID- 8568836
TI  - Exposure to polychlorinated biphenyls causes endothelial cell dysfunction.
AB  - Environmental chemicals, such as polychlorinated biphenyls (PCBs), may be
      atherogenic by disrupting normal functions of the vascular endothelium. To
      investigate this hypothesis, porcine pulmonary artery-derived endothelial cells
      were exposed to 3,3',4,4'-tetrachlorobiphenyl (PCB 77), 2,3,4,4',5
      pentachlorobiphenyl (PCB 114), or 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) for
      up to 24 hours. These PCBs were selected for their varying binding avidities with
      the aryl hydrocarbon (Ah) receptor and differences in their induction of
      cytochrome P450. PCB 77 and PCB 114 significantly disrupted, in a dose-dependent
      manner, endothelial barrier function by allowing an increase in albumin transfer
      across endothelial monolayers. These PCBs also contributed markedly to cellular
      oxidative stress, as measured by 2,7-dichlorofluorescin (DCF) fluorescence and
      lipid hydroperoxides, and caused a significant increase in intracellular calcium
      ([Ca2+]i) levels. Enhanced oxidative stress and [Ca2+]i in PCB 77- and PCB 114
      treated cells were accompanied by increased activity and content of cytochrome
      P450 1A and by a decrease in the vitamin E content in the culture medium. In
      contrast to the effects of PCB 77 and PCB 114, cell exposure to PCB 153 had no
      effect on cellular oxidation, [Ca2+]i, or endothelial barrier function. These
      results suggest that certain PCBs may play a role in the development of
      atherosclerosis by causing endothelial cell dysfunction and a decrease in the
      barrier function of the vascular endothelium. It is possible that interaction of
      PCBs with the Ah receptor and activation of the cytochrome P450 1A subfamily are
      involved in this pathology.

PMID- 8568837
TI  - DNA single-strand breakage in mammalian cells induced by redox cycling quinones
      in the absence of oxidative stress.
AB  - Quinone-induced cell death is often attributed to oxidative stress during which
      the formation of DNA strand breaks is thought to play an important role. In this
      study, extensive DNA damage was observed in human chronic myelogenous leukemic
      cells (K562) exposed for 15 minutes to low concentrations (15-100 microM) of the
      redox cycling quinones 2,3-dimethoxy-1,4-naphthoquinone (2,3-diOMe-1,4-NQ) and
      menadione. However, DNA strand breakage and cell death could not be attributed to
      oxidative stress as the intracellular level and redox status of the reducing
      equivalents NADP(H) and GSH were unaffected. The intracellular level of NAD+ was
      found to correlate well with the extent of DNA repair (r = 0.93, P < 0.02) and
      cell proliferation (r = 0.96, P < 0.01) in cells exposed to the quinones. In
      contrast, a significant decrease in the level of intracellular ATP was only
      observed in cells exposed to menadione (50-100 microM). These results suggest
      that redox cycling quinones are capable of inducing DNA damage in mammalian cells
      by a mechanism that does not involve oxidative stress. Following DNA damage, cell
      death is dependent on the availability of NAD+, which may be key to the rapid
      repair of strand breaks.

PMID- 8568838
TI  - Sphingolipid metabolites: members of a new class of lipid second messengers.

PMID- 8568839
TI  - The ion channel behavior of the nuclear pore complex.
AB  - Macromolecule-conducting pores have been recently recognized as a distinct class
      of ion channels. The poor role of macromolecules as electrical charge carriers
      can be used to detect their movement along electrolyte-filled pores. Because of
      their negligible contribution to electrical ion currents, translocating
      macromolecules reduce the net conductivity of the medium inside the pore, thus
      decreasing the measured pore ion conductance. In the extreme case, a large
      translocating macromolecule can interrupt ion flow along the pore lumen,
      reflected as a negligible pore conductance. Therefore, ion conductance serves as
      a measurement of macromolecular transport, with lesser values indicating greater
      macromolecular translocation (in size and/or number). Such is the principle of
      operation of the widely used Coulter counter, an instrument for counting and
      sizing particles. It has long been known that macromolecules translocate across
      the central channel of nuclear pore complexes (NPCs). Recently, large conductance
      ion channel activity (100-1000 pS) was recorded from the nuclear envelope (NE) of
      various preparations and it was suggested that NPCs may be the source of this
      activity. Despite its significance to understanding the regulation of
      transcription, replication, mRNA export, and thus gene expression of normal and
      pathological states, no report has appeared demonstrating that this channel
      activity corresponds to ion flow along the central channel of the NPC. Here we
      present such a demonstration in adult mouse cardiac myocyte nuclei. In agreement
      with concepts introduced for macromolecule-conducting channels, our patch clamp
      experiments showed that ion conductance is reduced, and thus that ion flow is
      restricted during translocation of macromolecules containing nuclear targeting
      signals. Ion flow was blocked by mAb414, a monoclonal antibody raised against a
      major NPC glycoprotein and known to localize on the NPC channel where it blocks
      macromolecular transport. These results also establish patch clamp as a useful
      technique for the measurement of macromolecular translocation along the large
      central channel of the NPC and provide a basis for the design of future
      investigations of nuclear signaling for control of gene activity, mRNA export for
      gene expression, as well as other processes subservient to NPC-mediated
      nucleocytoplasmic exchange.

PMID- 8568840
TI  - Patch clamp detection of transcription factor translocation along the nuclear
      pore complex channel.
AB  - Transcription factors (TFs) are cytoplasmic proteins that play an essential role
      in gene expression. These proteins form multimers and this phenomenon is thought
      to be one of the mechanisms that regulate transcription. TF molecules reach their
      DNA binding sites through the large central channel of the nuclear pore complex
      (NPC). However, the NPC channel is known to restrict the translocation of
      molecules > or = 20-70 kD. Therefore, during their translocation, TF molecules
      and/or their multimers may plug the NPC channel and thus, interrupt ion flow
      through the channel, with a concomitant reduction in the ion conductance of the
      channel (gamma). Here we show with patch clamp that gamma is reduced during
      translocation of three major TFs: c-Jun (40 kD), NF-kappa B (approximately equal
      to 50 kD), and SP1 (approximately equal to 100 kD). Within a minute, femtomolar
      concentrations of these proteins reduced gamma suggesting a purely mechanical
      interaction between single TF molecules and the inner wall of the NPC channel.
      NPCs remained plugged for 0.5-3 hr in the absence of ATP but when ATP was added,
      channel plugging was shortened to < 5 min. After unplugging, channel closures
      were rarely observed and the number of functional channels increased. The
      transcription factors also stabilized the NPCs as shown by the extended duration
      of the preparations which allowed recordings for up to 72 hr. These observations
      are the first direct demonstration of the important role of NPCs in mediating
      nuclear translocation of TFs and, therefore, in forming part of the mechanisms
      regulating gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8568841
TI  - Patch clamp and atomic force microscopy demonstrate TATA-binding protein (TBP)
      interactions with the nuclear pore complex.
AB  - The universal TATA-binding protein, TBP, is an essential component of the
      multiprotein complex known as transcription factor IID (TFIID). This complex,
      which consists of TBP and TBP-associated factors (TAFs), is essential for RNA
      polymerase II-mediated transcription. The molecular size of human TBP (37.7 kD)
      is close to the passive diffusion limit along the transport channel of the
      nuclear pore complex (NPC). Therefore, the possibility exists that NPCs restrict
      TBP translocation to the nuclear interior. Here we show for the first time, with
      patch-clamp and atomic force microscopy (AFM), that NPCs regulate TBP movement
      into the nucleus and that TBP (10(-15)-10(-10)M) is capable of modifying NPC
      structure and function. The translocation of TBP was ATP-dependent and could be
      detected as a transient plugging of the NPC channels, with a concomitant
      transient reduction in single NPC channel conductance, gamma, to a negligible
      value. NPC unplugging was accompanied by permanent channel opening at
      concentrations greater than 250 pM. AFM images demonstrated that the TBP
      molecules attached to and accumulated on the NPC cytosolic side. NPC channel
      activity could be recorded for more than 48 hr. These observations suggest that
      three novel functions of TBP are: to stabilize NPC, to force the NPC channels
      into an open state, and to increase the number of functional channels. Since TBP
      is a major component of transcription, our observations are relevant to the
      understanding of the gene expression mechanisms underlying normal and
      pathological cell structure and function.

PMID- 8568842
TI  - Hodgkin-Huxley analysis of a GCAC1 anion channel in the plasma membrane of guard
      cells.
AB  - A quantitative analysis of the time- and voltage-dependent kinetics of the Guard
      Cell Anion Channel (GCAC1) current in guard cell protoplasts from Vicia faba was
      analyzed using the whole-cell patch clamp technique. The voltage-dependent steady
      state activation of GCAC1 current followed a Boltzmann distribution. For the
      corresponding steady-state value of the activation variable a power of two was
      derived which yielded suitable fits of the time course of voltage-dependent
      current activation. The GCAC1 mediated chloride current could successfully be
      described in terms of the Hodgkin-Huxley equations commonly evoked for the Na
      channel in nerve. After step depolarizations from a potential in the range of the
      resting potential to potentials above the equilibrium potential for chloride an
      activation and also an inactivation could be described. The gating of both
      processes exhibited an inverse relationship on the polarity of the applied step
      potentials in the order of milliseconds. Deactivating tail currents decline
      exponentially. The presented analysis contributes to the understanding of the
      rising phase of the observed action potentials in guard cells of V. faba.
      Evidence is presented that the voltage-dependent kinetic properties of the GCAC1
      current are different from those properties described for the excitable anion
      currents in the plasmalemma of Chara corallina (Beilby & Coster, 1979a).

PMID- 8568843
TI  - DIDS increases K+ secretion through an IsK channel in apical membrane of
      vestibular dark cell epithelium of gerbil.
AB  - Vestibular dark cell epithelium secretes K+ via IsK channels in the apical
      membrane. The previous observation that disulfonic stilbenes increased the
      equivalent short circuit current (Isc) suggested that these agents might be
      useful investigative tools in this tissue. The present experiments were conducted
      to determine if the increase in Isc was associated with an increase in K+ flux
      and if the effect was directly on the IsK channel or indirectly via a cytosolic
      intermediary. Measurements of transepithelial K+ flux with the K(+)-selective
      vibrating probe and of changes in net cellular solute flux by measurements of
      epithelial cell height showed that 4,4'-diisothiocyanatostilbene-2,2'-disulfonic
      acid (DIDS) increased K+ flux by a factor of 1.96 +/- 0.71 and caused net solute
      efflux. The apical membrane was partitioned with a macropatch pipette and DIDS
      was applied either to the membrane outside the pipette, inside the pipette or to
      the entire apical membrane. DIDS inside the pipette increased the current across
      the patch, the membrane conductance, the slowly-inactivating (IsK) component of
      the membrane current and shifted the reversal voltage toward the equilibrium
      potential for K+. DIDS outside the patch decreased the patch current and
      conductance, consistent with shunting of current away from the membrane patch.
      These findings strongly support the notion that DIDS increases K+ secretion
      through IsK channels in the apical membrane of vestibular dark cell epithelium by
      acting directly on the channels or on a tightly colocalized membrane component.

PMID- 8568844
TI  - cGMP modulates transport across the ciliary epithelium.
AB  - cGMP reduced the short-circuit current (ISC) when applied to the aqueous surface
      of isolated rabbit and cat ciliary epithelia. cGMP either stimulated (in the
      rabbit) or had no effect (in the cat) on ISC when applied to the stromal surface.
      Addition of the cGMP-mediated hormone atrial natriuretic peptide (ANP) to the
      stromal (but not the aqueous) surface, or the nitrovasodilator sodium
      nitroprusside to the stromal surface, inhibited ISC across rabbit ciliary
      epithelium. The response to stromal cGMP was partly mediated by K+ channels at
      the stromal surface of the rabbit pigmented epithelial (PE) cells, since the
      effect was inhibited by stromal Ba2+, and was unaffected by Cl- replacement, by
      bumetanide, or by DIDS. In contrast, the response to aqueous cGMP was not likely
      mediated by changing either K+ or Cl- channels, based on transepithelial
      measurements of rabbit ciliary epithelium and complementary whole-cell patch
      clamping of cultured human nonpigmented ciliary epithelial (NPE) cells. The
      possibility of interacting effects between cGMP and cAMP in targeting the Na+,
      K(+)-exchange pump was also considered. Strophanthidin blocked the responses to
      either aqueous or stromal cGAMP. Applying 10 microns forskolin to generate
      endogenous cAMP enhanced the subsequent response to aqueous cGMP by approximately
      equal to 80%. We conclude that cGMP has at least two actions on the ciliary
      epithelium. The major effect may be to reverse cAMP-mediated inhibition of the
      NPE Na+ pumps at the aqueous surface of both rabbit and cat ciliary epithelia.
      The second effect is likely mediated by increasing K(+)-channel and pump activity
      of the rabbit PE cells at the stromal surface.

PMID- 8568845
TI  - Cellular mechanisms in activation of Na-K-Cl cotransport in nasal gland acinar
      cells of guinea pigs.
AB  - The cellular regulation mechanism of Na-K-Cl cotransport was studied in dispersed
      acinar cells of the guinea pig nasal gland by a microfluorimetric imaging method
      using the Na(+)-sensitive dye sodium-binding benzofuran isophthalate. Addition of
      1 micron acetylcholine (ACh) induced an immediate increase in intracellular Na+
      concentration ([Na+]i) by 36.7 +/- 9.9 mM, which was almost completely abolished
      by the addition of atropine. The increased [Na+]i after cholinergic stimulation
      was due to the external (Cl-)-dependent cotransport system (about 80% of the
      total Na+ influx) and the dimethyl amiloride-sensitive (Na+)-H+ exchange system
      (of about 20%). The ACh-induced increase in [Na+]i was dependent on extracellular
      Ca2+ and was prevented by pretreatment with 8-(N, N-diethylamino)octyl-3,4,5
      trimethoxybenzoate or O-O'-bis(2-aminophenyl)ethyleneglycol-N, N, N', N'
      tetraacetic acid tetraacetoxymethylester. Addition of 1 microns ionomycin
      mimicked the ACh-induced increase in [Na+]i which was dependent on external Cl-.
      Moreover, both a calmodulin antagonist trifluoperazine and a myosin light chain
      kinase inhibitor ML-7 reduced the ACh-induced response in [Na+]i. However, the
      following treatment did not affect the basal [Na+]i nor the ACh-induced increase
      in [Na+]i: (i) addition of dibutyryl cAMP, 8-Br-cGMP, or phorbol 12-myristate 13
      acetate, (ii) pretreatment of protein kinase inhibitors, H-89, H-8, H-7 or
      chelerythrine, (iii) prevention of cytosolic Cl- efflux by the addition of
      diphenylamine-2-carboxylic acid or, (iv) prevention of cytosolic K+ efflux by the
      addition of charybdotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8568846
TI  - Examination of the role of phosphorylation and phospholamban in the regulation of
      the cardiac sarcoplasmic reticulum Cl- channel.
AB  - Sarcoplasmic reticulum (SR) vesicles were prepared from either canine or sheep
      heart and fused into lipid bilayers to study their ionic channels. A 92 +/- 5 pS
      anion-selective channel was recorded in asymmetric 50 mM trans/250 mM cis CsCl
      buffer system. Reversal potentials and theoretical equilibrium potentials for Cl
      ions obtained under various experimental conditions allowed us to confirm the Cl-
      selectivity of this SR channel. The majority (69%) of channel recordings (n = 45)
      displayed steady-state kinetics and a slight voltage dependency of the open
      probability. However, 31% of the channels inactivated after their incorporation.
      We now report that the channel might be reactivated by depolarizing voltage
      steps. Furthermore, the use of either PKA or PKG in association with adequate
      phosphorylating buffers lengthens the deactivation process at the end of the
      voltage pulses, but does not prevent the inactivation. It was assumed that the
      change in gating mode was due to a voltage-sensitive association/dissociation
      mechanism with a phosphorylated protein of the SR membrane such as phospholamban
      (PL). We demonstrated that a specific monoclonal antibody raised against canine
      PL inhibited the activity of the channel and prevented its reactivation by
      depolarizing steps. 400 to 800 ng/ml of Anti-PL Ab consistently and sequentially
      turned off the channel activities. In contrast, heat inactivated Anti-PL Ab had
      no effect. We propose that phospholamban may be a primer of the SR Cl- channel
      whereby Cl- anions would play the role of counter-charge carrier during rapid
      Ca2+ release and Ca2+ uptake by the SR.

PMID- 8568847
TI  - Two types of A-channels in Lymnaea neurons.
AB  - The gating mechanism of A-channels of Lymnaea neurons and the effect of
      tetraethylammonium (TEA) on these channels were studied using macroscopic
      recording techniques. Along with the fast-inactivating A-current (Iaf) described
      earlier we found a slow-inactivating A-current (Ias) in some neurons of the
      visceral ganglion. Both currents have revealed similar activation kinetics, but
      differ in the inactivation kinetics and mechanisms. The inactivation kinetics of
      Ias were satisfactorily described by a sum of two exponentials with rate
      constants (tau -1) of 28 s-1 and 4.5 s-1 at V = -20 mV. Intracellular TEA reduced
      the peak amplitudes of Iaf and Ias and slowed the rate of the fast phase of
      inactivation of Iaf. This resulted in a crossover of the current traces in the
      presence and absence of TEA, as though it competes with the binding of the
      inactivating particle. The mechanism of the fast phase of inactivation of Iaf is
      similar to that of fast inactivation of the Shaker K+ channels which appears to
      be due to a ball-and-chain mechanism. The slow phases of inactivation of Iaf and
      Ias reveal properties characteristic of C-type inactivation shown in Shaker K+
      channels. A partially coupled model including three pathways for transition of a
      channel from the closed to open states accurately reproduces all of the
      experimental data. It has voltage-independent transitions to the inactivation
      states indicating that inactivation of A-current is not associated with charge
      movement through the membrane. The results suggest that Lymnaea A-channels seem
      to be heteromultimeric.

PMID- 8568848
TI  - Direct control of a large conductance K(+)-selective channel by G-proteins in
      adrenal chromaffin granule membranes.
AB  - We report here the presence of a Ca(2+)-independent K(+)-channel of large
      conductance in adrenal chromaffin cell secretory vesicle membranes which is
      controlled by inhibitory as well as stimulatory heterotrimeric GTP-binding
      proteins. Using antibodies against specific alpha subunits for immunoblot
      analysis, we were able to identify the presence of the inhibitory G(i)2 and G(i)3
      subtypes, as well as the stimulatory G(o) and Gs subtypes, but not G(i)1 in
      adrenal chromaffin granules. Furthermore, functional analysis of the K(+)-channel
      incorporated into planar lipid bilayers showed that GDP beta S and GTP gamma S
      have opposite effects on channel activity inducing interconversions between a low
      and a high open-probability state. Consistent with these findings, the same
      antibodies antagonized the effects of the nonhydrolyzable analogues on the open
      probability of the K(+)-channel.

PMID- 8568849
TI  - Characterization of a chloride channel reconstituted from cardiac sarcoplasmic
      reticulum.
AB  - We have characterized a voltage-sensitive chloride channel from cardiac
      sarcoplasmic reticulum (SR) following reconstitution of porcine heart SR into
      planar lipid bilayers. In 250 mM KCl, the channel had a main conductance level of
      130 pS and exhibited two substrates of 61 and 154 pS. The channel was very
      selective for Cl- over K+ or Na+ (PK+/PCl- = 0.012 and PNa+/PCl- approximately
      0.040). It was permeable to several anions and displayed the following sequence
      of anion permeability: SCN- > I- > NO3- approximately Br- > Cl- > F- > HCOO-.
      Single-channel conductance saturated with increasing Cl- concentrations (Km = 900
      mM and gamma max = 488 pS). Channel activity was voltage dependent, with an open
      probability ranging from approximately 1.0 around 0 mV to approximately 0.5 at
      +80 mV. From -20 to +80 mV, channel gating was time-independent. However, at
      voltages below -40 mV the channel entered a long-lasting closed state. Mean open
      times varied with voltage, from approximately 340 msec at -20 mV to approximately
      6 msec at +80 mV, whereas closed times were unaffected. The channel was not
      Ca(2+)-dependent. Channel activity was blocked by disulfonic stilbenes,
      arylaminobenzoates, zinc, and cadmium. Single-channel conductance was sensitive
      to trans pH, ranging from approximately 190 pS at pH 5.5 to approximately 60 pS
      at pH 9.0. These characteristics are different from those previously described
      for Cl- channels from skeletal or cardiac muscle SR.

PMID- 8568850
TI  - Properties of voltage-gated potassium currents of microglia differentiated with
      granulocyte/macrophage colony-stimulating factor.
AB  - Voltage-gated whole-cell currents were recorded from cultured microglial cells
      which had been developed in the presence of the macrophage/microglial growth
      factor granulocyte/macrophage colony-stimulating factor. Outward K+ currents (IK)
      were most prominent in these cells. IK could be activated at potentials more
      positive than -40 mV. Half-maximal activation of IK was achieved at -13.8 mV and
      half-maximal inactivation of IK was determined at -33.8 mV. The recovery of IK
      from inactivation was described by a time constant of 7.9 sec. For a tenfold
      change in extracellular K+ concentration the reversal potential of IK shifted by
      54 mV. Extracellularly applied 10 mM tetraethylammonium chloride reduced IK by
      about 50%, while 5 mM 4-aminopyridine almost completely abolished IK. Several
      divalent cations (Ba2+, Cd2+, Co2+, Zn2+) reduced current amplitudes and shifted
      the activation curve of IK to more positive values. Charybdotoxin (IC50 = 1.14
      nM) and noxiustoxin (IC50 = 0.89 nM) blocked IK in a concentration-dependent
      manner, whereas dendrotoxin and mast cell degranulating peptide had no effect on
      the current amplitudes. The outward K+ currents showed a frequency dependence
      when depolarizing pulses were applied at a frequency of 1 Hz. A frequency
      independent outward current (IK') characterized by the same activation behavior
      as IK was detected. IK' was blocked completely by 10 nM charybdotoxin or by 10 nM
      noxiustoxin. In contrast to its effect on IK, 10 mM tetraethylammonium chloride
      did not reduce IK'.

PMID- 8568851
TI  - Divalent cation channels activated by phenothiazines in membrane of rat
      ventricular myocytes.
AB  - Phenothiazines (PTZ) such as chlorpromazine (CPZ) or trifluoperazine (TPZ)
      induced a sustained divalent cation-permeable channel activity when applied on
      either side of inside-out patches or on external side of cell-attached patches of
      adult rat ventricular myocytes. The percentage of active patches was
      approximately 20%. In the case of CPZ, the Kd of the dose-response curve was 160
      microM. CPZ-activated channels were potential-independent in the physiological
      range of membrane potential and were permeable to several divalent ions (Ba2+,
      Ca2+, Mg2+, Mn2+). At least three levels of currents were usually detected with
      conductances of 23, 50 and 80 pS in symmetrical 96 mM Ba2+ solution and 17, 36
      and 61 pS in symmetrical 96 mM Ca2+ solution. Saturation curves corresponding to
      the three main conductances determined in Ba2+ symmetrical solutions (tonicity
      compensated with choline-Cl) gave maximum conductances of 36, 81 and 116 pS (with
      corresponding half-saturating concentration constants of 31.5, 38 and 34.5 mM).
      The corresponding conductance values were estimated to 1.7, 3.3 and 5.2 pS in
      symmetrical 1.8 mM Ba2+ and to 1.1, 2.4 and 3.7 pS in symmetrical 1.8 mM Ca2+
      (the value in normal Tyrode solution). Channels were poorly permeable to
      monovalent cations, such as Na, with a PBa/PNa ratio of 10. A PTZ-induced channel
      activity similar to that described in cardiac cells was also observed in cultured
      rat aortic smooth muscle cells but not in cultured neuroblastoma cells. PTZ
      activated channels described in cardiac cells appear very similar to the
      sporadically active divalent ion permeable channels described in a previous paper
      (Coulombe et al., 1989). Surprisingly, when 100 microM CPZ were applied to
      myocytes studied in the whole-cell configuration, and maintained at a holding
      potential of -80 mV in the presence of 24 mM external Ca2+ or Ba2+, no detectable
      macroscopic inward current could be observed, whereas the L-type Ca2+ current
      triggered by depolarizing pulses was markedly and reversibly reduced. The
      possible reasons are discussed.

PMID- 8568852
TI  - Hydrochlorothiazide action on the apical Cl-, Ca2+ and K+ conductances in rabbit
      gallbladder epithelium. Presence of an apamin-sensitive, Ca(2+)-activated K+
      conductance.
AB  - In the rabbit gallbladder epithelium, hydrochlorothiazide (HCTZ) was shown to
      inhibit the transepithelial NaCl transport and the apical Na(+)-Cl- symport, to
      depolarize the apical membrane potential and to enhance the cell-to-lumen Cl-
      backflux (radiochemically measured), this increase being SITS-sensitive. To
      better investigate the causes of the depolarization and the Cl- backflux
      increase, cells were punctured with conventional microelectrodes on the luminal
      side (incubation in bicarbonate-free saline at 27 degrees C) and the apical
      membrane potential (Vm) was studied either with prolonged single impalements or
      with a set of short multiple impalements. The maximal depolarization was of 3-4
      mV and was reached with 2.5 x 10(-4) M HCTZ. It was significantly enhanced by
      reducing luminal Cl- concentration to 30 mM; it was abolished by SCN-,
      furosemide, SITS; it was insensitive to DPC. SITS converted the depolarization
      into a hyperpolarization of about 4 mV; this latter was apamin, nifedipine and
      verapamil sensitive. It was concluded that HCTZ concomitantly opens apical Cl-
      and (probably) Ca2+ conductances and, indirectly, a Ca(2+)-sensitive, apamin
      inhibitable K+ conductance: since the intracellular Cl- activity is maintained
      above the value predicted at the electrochemical equilibrium, the opening of the
      apical Cl- conductance depolarizes Vm and enhances Cl- backflux. In the presence
      of apamin or verapamil, to avoid the hyperpolarizing effects due to HCTZ, the
      depolarization elicited by this drug was fully developed (7-10 mV) and proved to
      be Ca2+ insensitive. On this basis and measuring the transepithelial resistance
      and the apical/basolateral resistance ratio, the Cl- conductance opened by HCTZ
      has been estimated and the Cl- backflux increase calculate: it proved to be in
      the order of that observed radiochemically. The importance of this Cl- leak to
      the lumen in the overall inhibition of the transepithelial NaCl transport by HCTZ
      has been evaluated.

PMID- 8568853
TI  - Volume-activated chloride currents in pancreatic duct cells.
AB  - We have used the patch clamp technique to study volume-activated Cl- currents in
      the bicarbonate-secreting pancreatic duct cell. These currents could be elicited
      by a hypertonic pipette solution (osmotic gradient 20 mOsm/l), developed over
      about 8 min to a peak value of 91 +/- 5.8 pA/pF at 60 mV (n = 123), and were
      inhibited by a hypertonic bath solution. The proportion of cells which developed
      currents increased from 15% in freshly isolated ducts to 93% if the ducts were
      cultured for 2 days. The currents were ATP-dependent, had an outwardly rectifying
      current/voltage (I-V) plot, and displayed time-dependent inactivation at
      depolarizing potentials. The anion selectivity sequence was: ClO4 = I = SCN > Br
      = NO3 > Cl > F > HCO3 > gluconate, and the currents were inhibited to a variable
      extent by DIDS, NPPB, dideoxyforskolin, tamoxifen, verapamil and quinine.
      Increasing the intracellular Ca2+ buffering capacity, or lowering the
      extracellular Ca2+ concentration, reduced the proportion of duct cells which
      developed currents. However, removal of extracellular Ca2+ once the currents had
      developed was without effect. Inhibiting protein kinase C (PKC) with either the
      pseudosubstrate PKC (19-36), calphostin C or staurosporine completely blocked
      development of the currents. We speculate that cell swelling causes Ca2+ influx
      which activates PKC which in turn either phosphorylates the Cl- channel or a
      regulatory protein leading to channel activation.

PMID- 8568854
TI  - Extracellular ATP activates both Ca(2+)- and cAMP-dependent Cl- conductances in
      rat epididymal cells.
AB  - Activation of Ca2+ and cAMP-dependent Cl- conductances by extracellular ATP was
      studied using the whole-cell patch clamp technique. Immediately after addition of
      extracellular ATP (10 microM), activation of whole-cell Cl- current exhibiting
      delayed inactivation and activation kinetics at hyperpolarizing and depolarizing
      voltages, respectively, was observed. After prolonged activation, the kinetic
      characteristics of the ATP-induced Cl- current became time- and voltage
      independent. When applied to the later phase of the ATP-activated whole-cell
      current, the disulfonic acid stilbene DIDS (200 microM) could only inhibit 64% of
      the current while diphenylamine-dicarboxylic acid (DPC, 1 mM) completely
      inhibited it. Inclusion of a peptide inhibitor for protein kinase A (PKI, 10 nM)
      in the pipette solution blocked ATP-induced time- and voltage-independent current
      activation but did not affect the delayed activating and inactivating current
      activation but did not affect the delayed activating and inactivating current
      which could be totally blocked by DIDS. Anion selectivity sequence was determined
      in the presence of either PKI or DIDS and found to be significantly different.
      Increased pipette EGTA (10 mM) or treatment of the cells with trifluoperazine (40
      microM), an inhibitor of calmodulin, suppressed both types of ATP-induced Cl-
      currents. No current activation by ATP was observed when cells were dialyzed with
      the IP3 receptor blocker, heparin (10 ng/ml). These results suggest that
      extracellular ATP activates IP3-linked Ca(2+)-dependent regulatory pathway, which
      in turn activates cAMP-dependent pathway, leading to activation of both Ca2+ and
      cAMP-dependent Cl- conductances in epididymal cells.

PMID- 8568855
TI  - Effects of vasopressin and aldosterone on the lateral mobility of epithelial Na+
      channels in A6 renal epithelial cells.
AB  - We have previously demonstrated that apical Na+ channels in A6 renal epithelial
      cells are associated with spectrin-based membrane cytoskeleton proteins and that
      the lateral mobility of these channels, as determined by fluorescence photobleach
      recovery (FPR) analysis, is severely restricted by this association (Smith et
      al., 1991. Proc. Natl. Acad. Sci. USA 88:6971-6975). Recent data indicate that
      the actin component of the cytoskeleton may play a role in modulating Na+ channel
      activity (Cantiello et al., 1991. Am. J. Physiol. 261:C882-C888); however, it is
      unknown if the Na+ channel's linkage to the spectrin-based membrane cytoskeleton
      is also involved in regulating channel activity. In this study, we have used FPR
      to examine if the linkage of the Na+ channels to the membrane cytoskeleton is a
      site for modulation of Na+ channel activity in filter grown A6 cells by
      vasopressin and aldosterone. We hypothesized that if the linkage of the Na+
      channels to the membrane cytoskeleton is a site for regulation of Na+ channel
      activity by vasopressin and aldosterone, then hormone-mediated changes in either
      the membrane cytoskeleton or the affinity of the Na+ channel for the membrane
      cytoskeleton, should be reflected in changes in the lateral mobility and/or
      mobile fraction of Na+ channels on the cell surface. FPR revealed that although
      the rates of lateral mobility were not affected, there was a twofold increase in
      mobility fraction (f) of apical Na+ channels in aldosterone-treated (16 hr)
      monolayers (f = 32.31 +/- 5.42%) when compared to control (unstimulated) (f =
      14.2 +/- 0.77%) and vasopressin-treated (20 min) (f = 12.7 +/- 2.4%) monolayers.
      The twofold increase in mobile fraction of Na+ channels corresponds to the
      average increase in Na+ transport in response to aldosterone in A6 cells. The
      aldosterone-induced increase in Na+ transport and mobile fraction can be
      inhibited by the methylation inhibitor, 3-deazaadenosine, consistent with the
      hypothesis that a methylation event is involved in aldosterone induced
      upregulation of Na+ transport. We propose that the membrane cytoskeleton is
      involved in the aldosterone-mediated activation of epithelial Na+ channels.

PMID- 8568856
TI  - A voltage-dependent and pH-sensitive proton current in Rana esculenta oocytes.
AB  - Voltage clamp technique was used to study macroscopic ionic currents in Rana
      esculenta oocytes. Depolarization steps led to the activation of a single type of
      outward current (Iout) when contaminant potassium and calcium-dependent chloride
      currents were pharmacologically inhibited. The voltage threshold of Iout
      activation was 10 mV and this current, which did not inactivate, presented a
      deactivation the time constant of 73 +/- 21 msec (n = 26) corresponding to a
      membrane voltage of -60 mV. Its reversal potential (Erev) was dependent on the
      magnitude of the depolarization and also on pulse duration. These changes in Erev
      were thought to reflect intracellular ion depletion occurring during activation
      of the remaining outward current. Furthermore, the activation threshold of Iout
      was clearly affected by modifications in extracellular and intracellular H+
      concentrations. Indeed, intracellular alkalinization (evoked by external
      application of ammonium chloride) or extracellular acidification induced a
      rightward shift in the activation threshold while intracellular acidification
      (evoked by external application of sodium acetate) or extracellular
      alkalinization shifted this threshold toward a more negative value. Lastly, Iout
      was dramatically reduced by divalent cations such as Cd2+, Ni2+ or Zn2+ and was
      strongly decreased by 4 Aminopyridine (4-AP), well-known H+ current antagonists
      already described in many cell types. Therefore, it was suggested that the
      outward current was prominently carried by H+ ions, which may play a key role in
      the regulation of intracellular pH and subsequent pH dependent processes in Rana
      oocyte.

PMID- 8568857
TI  - Differential effect of triiodothyronine and thyroxine on liposomes containing
      cholesterol: physiological speculations.
AB  - The effect of thyroid hormones on the steady-state fluorescence polarization and
      on the release of the liposomal content was analyzed in liposomes composed of egg
      phosphatidylcholine and egg phosphatidyl choline:cholesterol in different molar
      ratios. Depending on liposome cholesterol composition, a dual effect of
      triiodothyronine was found. The fluorescence polarization of 1,6 diphenyl 1,3,5
      hexatriene or 1-(4-trimethylaminophenyl) 6 phenyl-1, 3, 5 hexatriene decreased by
      the addition of the hormone when cholesterol content was in the range from 0 to
      30 moles %, while it increased with cholesterol from 30 to 50 moles %. In the
      release experiments, the effect of triiodothyronine was also biphasic; the
      leakage was the highest at 0% and 50% and the lowest at 30 moles % of
      cholesterol. On the contrary, thyroxine was without effect on liposomes
      containing cholesterol from 30 to 50 mol %. This fact correlated with a lower
      incorporation of thyroxine, compared with that of triiodothyronine in liposomes
      containing up to 30 moles % of cholesterol. The fact that the above differential
      incorporation of thyroid hormones was also observed at physiological
      concentration and that most of the mammalian membrane cells have more than 25
      moles % of cholesterol have for physiological implications to the observations
      reported here.

PMID- 8568858
TI  - Evolutionary dynamics of non-coding sequences within the class II region of the
      human MHC.
AB  - About 40% (350 kb) of the human MHC class II region has been sequenced and a
      coordinated effort to sequence the entire MHC is underway. In addition to the
      coding information (22 genes/pseudogenes), the non-coding sequences reveal novel
      information on the organisation and evolution of the MHC as demonstrated here by
      the example of a 200 kb contig that has been analysed for local and global
      features. In conjunction with cross-species comparisons, our results present new
      evidence on the structure of isochores, the evolutionary dynamics of repeat
      mediated recombination and its effect on certain MHC encoded genes, and a higher
      than average degree of natural polymorphism that has implications for sequencing
      the human genome. We also report the finding of a class I-related pseudogene (HLA
      ZI) in the middle of the class II region, which provides the first direct
      evidence for DNA exchange between these two related regions in man.

PMID- 8568859
TI  - Disordered C-terminal domain of tyrosyl transfer-RNA synthetase: evidence for a
      folded state.
AB  - The C-terminal domain (residues 320 to 419) of tyrosyl-tRNA synthetase from
      Bacillus stearothermophilus (Bst-TyrRS) is necessary for the binding of tRNA(Tyr)
      but disordered in the crystal structure. Four different criteria showed that the
      isolated C-terminal domain of Bst-TyrRS was at least partially folded in
      solution. Its spectrum of circular dichroism was compatible with a high content
      of secondary structure elements (56% of its residues) and these structural
      elements disappeared in 7.5 M urea. It was unfolded by urea along a unique
      transition, around 6.0 M, according to the variations in the fluorescence of its
      tyrosine residues and in its electrophoretic mobility through transverse gradient
      gels. It was denatured by heat with a temperature of half-precipitation in 30
      minutes that was equal to 67.9 degrees C and close to the Bst-TyrRS one, 68.7
      degrees C. Its transitions of denaturation by urea or temperature were weakly
      cooperative. The C-terminal domains of the TyrRSs from Escherichia coli (Eco
      TyrRS) and B. stearothermophilus could be genetically exchanged without a
      significant loss of aminoacylation activity. A hybrid between the N-terminal
      domain of Bst-TyrRS and the C-terminal domain of Eco-TyrRS was precipitated by
      heat in 30 minutes following two transitions: 83% of the molecules were
      precipitated with a temperature of half-transition (51.6 degrees C) close to the
      Eco-TyrRS one (48.6 degrees C). The remainder was precipitated with a temperature
      of half-transition (65.5 degrees C) close to the Bst-TyrRS one (67.2 degrees C)
      or that of its N-terminal domain (68.0 degrees C). These results showed that the
      C-terminal domain of Eco-TyrRS could undergo a transition from a soluble active
      conformation to an insoluble one. The denaturations of Bst-TyrRS and of its N
      terminal domain by urea occurred with two successive transitions, around 4 M and
      6 M, and thus according to a complex mechanism.

PMID- 8568860
TI  - Rules for coupled expression of regulator and effector genes in inducible
      circuits.
AB  - The induction of effector genes that encode enzymes is often controlled by the
      protein product of a regulator gene that is directly involved in the control of
      its own expression. This coupling of elementary gene circuits can lead to three
      patterns of regulator and effector gene expression. As effector gene expression
      increases, regulator gene expression can increase, remain the same, or decrease,
      and these are referred to as directly coupled, uncoupled, or inversely coupled
      patterns. To determine the relative merits of each pattern, we have constructed
      appropriate mathematical models for the alternative gene circuits and made well
      controlled comparisons using a priori criteria to evaluate their functional
      effectiveness. We have considered both negatively and positively controlled
      systems that are induced by an intermediate of the regulated pathway. Different
      results are obtained in the two cases. Our results indicate that direct coupling
      is better than inverse coupling or uncoupling for negatively controlled systems,
      while inverse coupling is better than the other two patterns for positively
      controlled systems. These optimal forms of coupling promote a fast response to
      inducer. Our results also indicate that realization of the optimal forms of
      coupling is influenced by the subunit structure of regulator proteins and
      requires a low capacity for induction, i.e. the ratio of maximal to minimal level
      of effector gene expression is small. These results lead to testable predictions,
      which we have compared with experimental data from over 30 systems.

PMID- 8568861
TI  - Identification of the binding site for acidic phospholipids on the pH domain of
      dynamin: implications for stimulation of GTPase activity.
AB  - It has recently been suggested that pleckstrin homology (PH) domains bind
      specifically to phospholipids, with phosphatidylinositol-4,5-bisphosphate
      (PtdIns(4,5)P2) being most strongly bound. This observation suggests that PH
      domains may be responsible for membrane association of proteins in which they
      occur. Further, this membrane association may be regulated by enzymes that modify
      lipid head groups to which PH domains may bind. We have studied the binding of
      phospholipids to the PH domain of human dynamin, a 100 kDa GTPase that is
      involved in the initial stages of endocytosis. We describe a rapid method for
      screening PH domain/ligand interactions that gives precise binding constants. We
      confirm that PtdIns(4,5)P2 can bind to dynamin PH domain, although not in an
      aggregated state. Using NMR spectroscopy, we have mapped a specific site on the
      surface of dynamin PH domain of which binding of gIns(1,4,5)P3 (the head-group
      skeleton of PtdIns(4,5)P2) occurs. The relative affinity of acidic phospholipids
      for dynamin PH domain correlates with their ability to activate the GTPase of
      dynamin. We propose, therefore, that the interaction of these phospholipids with
      dynamin is likely to occur via the PH domain. Given the fact that PH domains are
      often found in proteins associated with GTPase activity, or in guanine nucleotide
      exchange factors, we suggest that one role of PH domains may be to couple
      phosphatidylinositol signalling to GTP hydrolysis.

PMID- 8568862
TI  - Three-dimensional reconstruction of the chlorocruorin of the polychaete annelid
      Eudistylia vancouverii.
AB  - The chlorocruorin of the polychaete Eudistylia vancouverii observed in the
      electron microscope in vitreous ice, was subjected to a three-dimensional (3D)
      reconstruction by the random conical tilt series method. The 3D volume with a
      resolution of 35 A reconstructed from 1062 images in top, side and intermediate
      view orientations has a D6 point-group symmetry. It possesses the characteristic
      hexagonal bilayer (HBL) appearance. Each hexagonal half-molecule comprises size
      hollow globular substructures (HGS) presumed to correspond to the dodecameric
      subunits. In projection, when the molecule is viewed along its 6-fold axis, the
      two halves are not perfectly eclipsed. The vertices of the upper hexagonal layer
      are 14 degrees rotated clockwise compared with those of the lower half. At a
      threshold displaying 100% of the expected molecular volume, the 3D volume
      contains in its center a flat hexagonal central mass disconnected from the rest
      of the volume. Several types of connections, termed c1 through c4, are visible
      between the HGSs. The c1 and c2 connections link the HGSs of the same hexagonal
      half-molecule. The c3 connections make a hexagonal inner bracelet linking the
      HGSs of each half-molecule. The c4 connections link pairs of HGSs superposed in
      the two hexagonal layers. Because of the half-molecules rotation around the 6
      fold axis, the two HGSs linked by a c4 connection are not exactly superposed. It
      is proposed that the c3 and c4-connection bodies and less probably the flat
      central hexagonal mass are composed of chloroheme-deficient linker chains. When
      eroding the 3D volume by raising the threshold, the HGS appears composed of three
      elongated structures likely containing four globin chains. In addition, they show
      an approximate 3-fold symmetry. At high thresholds, two of these masses, dumbbell
      shaped, separate into globular masses while the third structure remains compact
      as long as 1% of the molecular volume is displayed.

PMID- 8568863
TI  - Mass spectrometric composition and molecular mass of Lumbricus terrestris
      hemoglobin: a refined model of its quaternary structure.
AB  - Sedimentation equilibrium measurements and scanning transmission electron
      microscopy (STEM) mass mapping of the extracellular, hexagonal bilayer hemoglobin
      (HBL Hb) of the earthworm Lumbricus terrestris provided masses of 3.41 to 3.66
      MDa and 3.56 (+/- 0.13) MDa, respectively. The Hb also contains 57.2 (+/- 6.0)
      moles of tightly bound Ca per mole of protein. The Hb and its subunits obtained
      by dissociation, in native, dehemed and reduced carbamidomethylated forms, were
      subjected to electrospray ionization mass spectroscopy (ESI-MS). Maximum entropy
      deconvolution identified three groups of peaks, at approximately 16 kDa, 24 to 32
      kDa and approximately 53 kDa corresponding to the monomer subunit M (globin chain
      d), four linker subunits and the disulfide-bonded trimer T (globin chains a + b +
      c). Subunit M consisted of three components, d1 (15, 992.4), d2 (15, 978.0) and
      d3 (15, 962.1) (+/- 1.0 Da), with relative intensities 1.0:5:0.3, respectively.
      Subunit T consisted of four major components, T1 (52, 922.6), T2 (52, 760.0), T3
      (52, 598.5) and T4 (52, 435.4) (+/- 4.0 Da), with relative intensities
      0.6:1.0:0.2:0.7, respectively. ESI-MS of carbamidomethylated T, demonstrated
      that, unlike chains b (16, 254.4) and c (17, 289.2), chain a exists as a series
      of four, hexose-connected, glycosylated isoforms, a1 to a4 (19, 389.9, 19, 227.4,
      19, 065.3 and 18, 902.9) (+/- 1.0 Da). The mass differences between the
      deglycosylated chain a (17, 524.0) and a1 to a4 correspond to glycan side-chains
      (GlcNAc)2 (Man)n (n = 6 to 9). Four groups of peaks were observed in the 24 to 32
      kDa region. Linkers L1a (27, 540.8) and L1b (27, 702.4) (+/- 2.0 Da) are isoforms
      of L1 (25, 837.5 in N-deglycosylated Hb) with glycan side-chains (GlcNAc)2 (Man)n
      (n = 8,9). Linkers L2 (32, 104.3 (+/- 5.0) Da) and L3 (24, 912.9 (+/- 2.0) Da)
      occur as single species. Linkers L4a to L4c (24, 019.0, 24, 102.3 and 24, 169.9)
      (+/- 2.0 Da) with relative intensities 1.0:0.8:0.8, have not been identified
      previously. From ESI-MS relative intensities, L1:L2:L3:L4 = 0.6:0.4:1.0:0.5 and
      globin linker = 0.78:0.22. HPLC of Lumbricus Hb provided a globin linker =
      0.73:0.27 (+/- 0.02) and a heme content of 2.52 (+/- 0.14) wt%. A model is
      proposed for the HBL structure, wherein 12 213.4 kDa dodecamers (144 globin
      chains, 2561 kDa) decorate a hexagonal framework of 36 linker chains (12L1 + 6L2
      + 12L3 + 6L4) to provide a total mass of 3.531 MDa, each dodecamer being in
      contact with three linker subunits.

PMID- 8568864
TI  - Molecular symmetry of the dodecamer subunit of Lumbricus terrestris hemoglobin.
AB  - The principal functional subunit of the approximately 3500 kDa extracellular
      Lumbricus terrestris hemoglobin is a 213 kDa dodecamer of four chemically
      distinct globin chains, consisting of a non-covalent complex of three trimer
      submits (disulfide-bonded chains a, b and c) and three monomer subunits (chain
      d). X-ray diffraction of crystals of the dodecamer grown at neutral pH, were
      found to be monoclinic, with the unit cell dimensions: a = 112.3 A, b = 190.0 A,
      c = 69.6 A, beta = 102.0 degrees with h + k + l = 2n + 1 absent, characteristic
      of space group I121. In addition, these crystals exhibit a pseudo trigonal P321
      symmetry with unit cell dimensions a = 190.5 A, b = 190.5 A, c = 69.5 A, gamma =
      120.0 degrees. Assuming that the assymetric unit contains an entire dodecamer, a
      model of the latter was constructed that satisfies the symmetry of the trigonal
      pseudo cell and is consistent with the symmetry of the I121 crystallographic
      cell. The resulting model has strong implications concerning the hexagonal
      bilayer structure of the native hemoglobin.

PMID- 8568865
TI  - Crystal structure of Citrobacter freundii restriction endonuclease Cfr10I at 2.15
      A resolution.
AB  - The X-ray crystal structure of Citrobacter freundii restriction endonuclease
      Cfr10I has been determined at a resolution of 2.15 A by multiple isomorphous
      replacement methods and refined to an R-factor of 19.64%. The structure of Cfr10I
      represents the first structure of a restriction endonuclease recognizing a
      degenerated nucleotide sequence. Structural comparison of Cfr10I with previously
      solved structures of other restriction enzymes suggests that recognition of
      specific sequence occurs through contacts in the major and the minor grooves of
      DNA. The arrangement of the putative active site residues shows some striking
      differences from previously described restriction endonucleases and supports a
      two-metal-ion mechanism of catalysis.

PMID- 8568866
TI  - NMR structure of HMfB from the hyperthermophile, Methanothermus fervidus,
      confirms that this archaeal protein is a histone.
AB  - The three-dimensional structure of the recombinant histone rHMfB from
      Methanothermus fervidus, an archaeon that grows optimally at 83 degrees C, has
      been determined by nuclear magnetic resonance methods. This is only the third
      structure of a protein from a hyperthermophilic organism (optimal growth at
      temperatures above 80 degrees C). Signal assignments were made using a
      combination of homonuclear-correlated, 15N-double resonance and 15N, 13C triple
      resonance NMR experiments. Long range dipolar interactions for the symmetric
      homodimer were identified from two-dimensional 13C-double half-filtered and three
      dimensional 13C-filtered NMR data obtained for a heterolabeled-dimer. A family of
      33 structures was calculated using DSPACE with a total of 609 NOE-derived
      interproton distance restraints, including 22 intraresidue, 192 sequential, 300
      medium-range (two to five residues), 86 long-range intramolecular (more than five
      residues) and 112 intermolecular distance restraints. The monomer subunits
      consist of three alpha-helices, extending from residues Pro4 to Ala15 (helix I),
      Ser21 to Ala50 (helix II) and Lys56 to Lys68 (helix III), as well as two short
      segments of beta-strand comprised of residues Arg19 to Ser21 and Thr54 to Ile55.
      Helices I, II and III contain N-terminal capping boxes, and helices I and II
      contain C-terminal caps. The structure of the (rHMfB)2 dimer appears very similar
      to the dimer subunits within the histone core octamer of the chicken nucleosome.
      The presence of a canonical "histone fold" motif in rHMfB is consistent with the
      HMf family of archaeal histones and the eukaryal nucleosome core histones having
      evolved from a common ancestor. The (rHMfB)2 dimer contains several structural
      features that may impart thermal stability (or non-lability), including two novel
      hydrophobic "proline Ncaps", four interhelical hydrogen bonds and short N- and C
      terminal disordered tails.

PMID- 8568867
TI  - AV77 hinge mutation stabilizes the helix-turn-helix domain of trp repressor.
AB  - The structure and dynamics of the AV77 holorepressor have been studied using
      nuclear Overhauser enhancement spectroscopy (NOESY). By comparing NOE crosspeaks
      as well as proton chemical shifts, we find no evidence for any substantial
      difference between the wild-type and AV77 repressor structures. In addition,
      however, we have measured the rapid amide proton exchange rates for the DNA
      binding region of the apo and holo forms of the mutant and wild-type repressors
      using proton relaxation and saturation transfer techniques. We find that the
      hydrogen bonded amide protons in the DNA binding regions are stabilized for the
      most part by at least an order of magnitude for both forms of the mutant
      repressors. This is compared to a three to five fold stabilization of the holo
      wild-type molecule over the apo form. As the AV77 mutant is observed to be a
      superrepressor in vivo, we ascribe the enhanced activity of this mutant to a
      decrease in the instability of the DNA binding domain. We therefore suggest that
      the inherent instability of this domain in the wild-type molecule is needed for
      efficient regulation of the repressor by its corepressor, L-tryptophan, and in
      addition may allow for recognition of a broad range of operators.

PMID- 8568868
TI  - Further evidence on the equilibrium "pre-molten globule state": four-state
      guanidinium chloride-induced unfolding of carbonic anhydrase B at low
      temperature.
AB  - Equilibrium guanidinium chloride-induced unfolding of bovine carbonic anhydrase
      NB has been investigated by a combination of optical methods with size-exclusion
      chromatography. It has been shown that, as in the case of staphylococcal beta
      lactamase, bovine carbonic anhydrase B unfolds at low temperature through two
      equilibrium intermediates; the molten globule and the pre-molten globule states.
      This pre-molten globule state has a hydrodynamic volume no more than twofold
      larger than that of the native state, i.e. is relatively compact. It has a
      pronounced far UV CD spectrum, suggesting the presence of a substantial secondary
      structure. It binds 8-anilinonaphthalene-1-sulphonate (though weaker than the
      molten globule state), which suggests the formation of solvent-exposed clusters
      of non-polar groups. Thus, this novel state of protein molecules shares a number
      of properties with the "burst" kinetic intermediate of protein folding and can be
      considered as its equilibrium counterpart.

PMID- 8568869
TI  - Calcium binding properties of an epidermal growth factor-like domain pair from
      human fibrillin-1.
AB  - Ca2+ binding epidermal growth factor-like (EGF-like) domains are found in a large
      number of extracellular proteins with diverse functions, including those involved
      in blood coagulation, determination of cell fate, cell adhesion and connective
      tissue architecture. Their importance is emphasised by the identification of
      mutations in these domains in patients with haemophilia B (defective in
      coagulation factor IX) and the Marfan syndrome (defective in the connective
      tissue protein fibrillin-1). The X-ray crystal structure of a single Ca2+ binding
      EGF-like domain from human coagulation factor IX has recently been solved. It
      shows that the Ca2+ ligands form a pentagonal bipyramid, where one ligand is
      provided by an adjacent (N-terminal) EGF-like domain in the crystal. The N and C
      termini of the neighbouring domains are only approximately 4 angstrum apart,
      hence the crystal packing has been proposed as a model for the association of
      contiguous EGF-like domains in proteins. Since the adjacent EGF-like domain in
      the crystal, although close, is not covalently linked to its neighbour, this
      model requires verification. In this study we have expressed and purified a Ca2+
      binding EGF-like domain pair from human fibrillin-1 and used an in vitro
      refolding system to obtain protein with the correct EGF fold. The Ca2+ binding
      properties of the protein have been investigated by two-dimensional NMR. The
      affinity of the C-terminal domain for Ca2+ is approximately 25-fold higher than
      that of the N-terminal domain, consistent with the two Ca2+ binding sites having
      different local environments. In addition, these data provide the first direct
      experimental evidence that Ca2+ plays a major role in defining the interdomain
      linkage in multiple repeats of Ca2+ binding EGF-like domains.

PMID- 8568870
TI  - Oxygen transport by fetal bovine hemoglobin.
AB  - The functional properties of fetal bovine hemoglobin have been studied as a
      function of temperature, chloride and 2,3-diphosphoglycerate (DPG) concentration.
      The fetal bovine erythrocyte has six times the concentration of the allosteric
      modulator DPG compared with the adult cell, and yet the oxygen affinity of the
      fetal hemoglobin still exceeds that of the adult molecule at the respective
      physiological concentration of DPG and at physiological temperature. We find that
      the allosteric modulator strongly affects the enthalpy of oxygen for the fetal
      hemoglobin but not for the adult protein. We propose that this may be an
      important mechanism for the exchange of heat from mother to fetus. In particular,
      under stripped conditions the oxygen affinity of fetal bovine Hb is considerably
      higher than that of the adult hemoglobin. Due to the higher DPG concentration
      that characterizes fetal bovine erythrocytes this difference is almost abolished
      in the presence of the respective physiological concentration of DPG and at 20
      degrees C. However, on going from 20 degrees C to 37 degrees C, the difference in
      O2 affinity between the two hemoglobins is restored, as it should if oxygen has
      to be transferred from maternal to fetal blood, by virtue of the lower overall
      heat of oxygenation (delta H) displayed by fetal Hb when in the presence of DPG
      at physiological concentration. This behavior is reminiscent of that of human
      fetal Hb and outlines the role of temperature and of its interplay with
      heterotropic ligands in the modulation of hemoglobin function to fully meet the
      physiological needs of the organism.

PMID- 8568871
TI  - Automatic classification and analysis of alpha alpha-turn motifs in proteins.
AB  - An automatic procedure for the classification of short protein fragments,
      representing turn motifs between two consecutive secondary structures, is
      presented. This procedure has two steps. Fragments of given length are first
      grouped on the basis of their backbone dihedral angle values, and then clustered
      as a function of the root-mean-square deviation of their superimposed backbone
      atoms. The classification procedure identifies 63 families of turn motifs with at
      least five members, in a dataset of 141 proteins. A detailed analysis is
      presented of the ten identified alpha alpha-turn families, of which four
      correspond to novel motifs. The sequence and structure features that characterize
      these families are described. It is found that some features are conserved within
      the fragments belonging to the same family, but their environment in the parent
      protein varies considerably. N-capping interactions and helix stop signals are
      encountered in a number of families, where they seem to stabilize the motif
      conformation. In two families, one with three residues in the loop, and one with
      four, an appreciable fraction of the members displays both types of
      characteristic helix end interactions in the same motif. Interestingly, contrary
      to most other alpha alpha-turns, the relative frequency of these two motifs is
      much higher than that of short protein segments with the same loop conformation.
      Furthermore, the family with three residues in the loop includes the helix-turn
      helix motif known to bind DNA. It seems to be the only one among the ten
      identified families that can be related to biological function.

PMID- 8568872
TI  - Description of RNA folding by "simulated annealing".
AB  - An algorithm is proposed which describes the thermodynamically as well as the
      kinetically controlled folding process of RNA. The algorithm, based on a special
      Monte Carlo procedure known as "Simulated Annealing", takes into account the
      probabilities for opening and closing of single base-pairs. Thus, the algorithm
      is able to reach structures and structure distributions near the global minimum
      of structure space, and is not restricted by the tendency to halt in local
      minima. Three types of structural folding processes may be analysed by this
      algorithm. Firstly, using thermodynamic data, structure ensembles comparable to
      those obtained by dynamic programming are achieved. Secondly, using kinetic data,
      the processes of structure formation and structural rearrangement may be
      simulated. Thirdly, additionally taking into account RNA polymerase chain
      elongation rates, the process of "sequential folding" during transcription may be
      described. Analysis of all types of structural folding and refolding is performed
      for RNA sequences related to potato spindle tuber viroid (PSTVd). The computed
      results are in accordance with experimental data and biological functions known
      for PSTVd.

PMID- 8568873
TI  - Isolation of high-affinity monomeric human anti-c-erbB-2 single chain Fv using
      affinity-driven selection.
AB  - The use of antibodies to target tumor antigens has had limited success, partially
      due to the large size of IgG molecules, difficulties in constructing smaller
      single chain Fv (scFv) antibody fragments, and immunogenicity of murine
      antibodies. These limitations can be overcome by selecting human scFv directly
      from non-immune or semi-synthetic phage antibody libraries; however, the
      affinities are typically too low for therapeutic application. For hapten
      antigens, higher-affinity scFv can be isolated from phage antibody libraries
      where the VH and VL genes of a binding scFv are replaced with repertoires of V
      genes (chain shuffling). The applicability of this approach to protein binding
      scFv is unknown. For this work, chain shuffling was used to increase the affinity
      of a non-immune human scFv, which binds the glycoprotein tumor antigen c-erbB-2
      with an affinity of 1.6 x 10(-8) M. The affinity of the parental scFv was
      increased sixfold (Kd = 2.5 x 10(-9) M) by light-chain shuffling and fivefold (Kd
      = 3.1 x 10(-9) M) by heavy-chain shuffling, values comparable to those for
      antibodies against the same antigen produced by hybridomas. When selections were
      performed on antigen immobilized on polystyrene, spontaneously dimerizing scFv
      were isolated, the best of which had only a slightly lower Kd than wild type (Kd
      = 1.1 x 10(-8) M). These scFv dimerize on phage and are preferentially selected
      as a result of increased avidity. Compared to scFv which formed only monomer,
      dimerizing scFv had mutations located at the VH-VL interface, suggesting that VH
      VL complementarity determines the extent of dimerization. Higher-affinity
      monomeric scFv were only obtained by selecting in solution using limiting
      concentrations of biotinylated antigen, followed by screening mutant scFv from
      bacterial periplasm by koff in a BIAcore. Using the proper selection and
      screening conditions, protein binding human scFv with affinities comparable to
      murine hybridomas can be produced without immunization.

PMID- 8568874
TI  - The mechanism of CAP-lac repressor binding cooperativity at the E. coli lactose
      promoter.
AB  - The cyclic AMP receptor protein (CAP) and lactose repressor bind their regulatory
      sites in the lactose promoter with moderate cooperativity (omega C101 = 11.8(+/-
      3.7)). This cooperativity is significantly reduced by the removal of DNA located
      upstream of the CAP binding site or by substitution of the dimeric lacI-18 mutant
      repressor for the wild-type tetrameric protein. These results are consistent with
      a mechanism of interaction in which CAP bends the DNA and the lac repressor binds
      simultaneously to its operator site and to promoter-distal sequences. Similar
      values of omega C101 were obtained with a promoter truncation containing the O3
      pseudooperator site and one in which the site is destroyed, suggesting that DNA
      contacts distal to the O3 site are necessary for cooperative binding.

PMID- 8568875
TI  - In vitro evolution of the DNA binding sites of Escherichia coli methionine
      repressor, MetJ.
AB  - The SELEX procedure was used to study the recognition between the E. coli
      methionine repressor (MetJ) and its DNA binding sites. DNA ligands with high
      affinity for either the holo-repressor or apo-repressor were isolated from a pool
      of molecules randomized over 20 base-pairs. Among 90 DNA ligands selected by holo
      repressor binding, roughly 90% contain variations of two tandem, perfect eight
      base-pair Met-boxes, which are the consensus deduced from natural met operators.
      Base-pairs that are important, for specific interactions with the protein are
      highly conserved. The data also reveal the importance of the non-contacted
      operator base-pairs in facilitating the conformational changes in the operator
      which must occur for repressor binding. There are also effects due to the
      sequences of the base-pairs immediately flanking the operator site. DNA ligands
      selected by apo-repressor share a very similar, but not identical, consensus with
      that selected by holo-repressor, suggesting that the corepressor does not greatly
      alter the specificity of repressor binding.

PMID- 8568876
TI  - Enzymatic formation of modified nucleosides in tRNA: dependence on tRNA
      architecture.
AB  - Information is still quite limited concerning the structural requirements in tRNA
      molecules for their post-transcriptional maturation by base and ribose
      modification enzymes. To address this question, we have chosen as the model
      system yeast tRNAAsp that has a known three-dimensional structure and the in vivo
      modifying machinery of the Xenopus laevis oocyte able to act on microinjected
      tRNA precursors. We have systematically compared the modification pattern of wild
      type tRNAAsp with that of a series of structural mutants (21 altogether) altered
      at single or multiple positions in the D-, T-and the anticodon branch, as well as
      in the variable region. The experimental system allowed us to analyze the effects
      of structural perturbations in tRNA on the enzymatic formation of modified
      nucleosides at 12 locations scattered over the tRNA cloverleaf. We found that the
      formation of m1G37 and psi 40 in the anticodon loop and stem and psi 13 in the D
      stem, were extremely sensitive to 3D perturbations. In contrast, the formation of
      T54, psi 55 and m1A58 in the T-loop, m5C49 in the T-stem and m2G6 in the amino
      acid accepting stem were essentially insensitive to change in the overall tRNA
      architecture; these modified nucleosides were also formed in appropriate
      minimalist (stems and loops) tRNA domains. The formation of m2G26 at the junction
      between the anticodon and the D-stem, of Q34 and manQ34 in the anticodon loop
      were sensitive only to drastic structural perturbation of the tRNA. Altogether,
      these results reflect the existence of different modes of tRNA recognition by the
      many different modifying enzymes. A classification of this family of maturation
      enzymes into two major groups, according to their sensitivities to structural
      perturbations in tRNA, is proposed.

PMID- 8568877
TI  - Coupling protein design and in vitro selection strategies: improving specificity
      and affinity of a designed beta-protein IL-6 antagonist.
AB  - The minibody is a designed small beta-protein conceived to enable the
      construction of large libraries of minimal discontinuous epitopes displayed on
      the surface of filamentous phage. The 61 residue molecule consists of three
      strands from each of the two beta-sheets of the variable domain of
      immunoglobulins packed face to face, along with the exposed H1 and H2
      hypervariable regions. We have previously shown that from a minibody repertoire
      of more than 50 million molecules displayed on phage, we were able to select a
      minibody with micromolar affinity for human interleukin-6 that behaves as a
      selective cytokine antagonist. The minibody exposes a surface composed of two
      constrained loops, which provides the possibility of improving IL-6 binding and
      specificity by swapping the hypervariable regions, followed by further selection.
      We established experimental conditions for "stringent" selection such as
      monovalent phage display, competitive selection and epitope masking. Here, we
      show that by virtue of the optimization/selection process, we have isolated a
      minibody with improved antagonistic potency and greater specificity. Furthermore,
      using hIL-6 mutants carrying amino acid substitutions in distinct surface sites
      it was possible to carefully define the cytokine region that binds the minibody.

PMID- 8568878
TI  - Molecular organization and alternative splicing in zipper, the gene that encodes
      the Drosophila non-muscle myosin II heavy chain.
AB  - Genomic sequence of the entire zipper gene, that encodes non-muscle myosin II
      heavy chain (MHC) in Drosophila melanogaster, reveals a new, differentially
      spliced exon in this essential locus and identifies a molecular lesion that is
      responsible for a severe embryonic lethal zipper allele. There are two
      alternative splices in the head domain. The first is present in the 5'
      untranslated sequence which, when employed, produces an N-terminal extension of
      45 amino acids (aa). This splicoform produces a protein that is stable in flies
      but less prevalent than the isoform that lacks the extension. The second
      alternative exon (40 aa) is close to the nucleotide binding pocket. The position,
      size and sequence of this exon is conserved in D. simulans and putative
      alternative exons of different size (7 to 16 aa) but identical position have been
      reported for other myosins throughout phylogeny. The functional significance of
      neither alternative splice is clear. Sequence analysis of genomic DNA identifies
      the lesion responsible for zipIIF107, one of the original severe embryonic lethal
      zipper alleles. Our primary structural data confirm and correct our previous
      sequence of the cDNA, establish the spatial relationship between zipper and
      unzipped (the gene originally thought to have been disrupted in zipper
      mutations), and provide a high resolution template for the precise mapping of
      mutations.

PMID- 8568879
TI  - The N-terminal domain of the rne gene product has RNase E activity and is non
      overlapping with the arginine-rich RNA-binding site.
AB  - The rne gene of Escherichia coli encodes a 118 kDa protein that has ribonuclease
      E (RNase E) activity and binds RNA. A functional rne gene product is essential
      for cell viability and for the processing and/or decay of a variety of RNA
      species, including 9 S RNA, mRNA and RNAI, the antisense RNA regulator of ColE1
      type plasmid replication. By testing the ability of different segments of the Rne
      protein to catalyze RNA cleavage and to bind RNA, we found that the N-terminal
      half (residues 1 to 498) of Rne contains a catalytic function sufficient for site
      specific cleavage of oligoribonucleotides and complex RNAs. The C-terminal half
      of the protein, which contains both an arginine-rich region (residues 597 to 684)
      that we show binds RNA and a segment that is essential for cell viability
      (residues 844 to 1061), had no detectable endoribonucleolytic activity. Our
      results, which map the catalytic domain of RNase E, indicate the existence of
      discrete functional domains within the multifaceted Rne protein.

PMID- 8568880
TI  - Allosteric control by ATP of non-folded protein binding to GroEL.
AB  - Co-operativity in ATP hydrolysis by GroEL can be described by a model in which
      each ring of GroEL is in equilibrium between a low (T) and high (R) affinity
      state for ATP. According to this model, the GroEL double-ring is in equilibrium
      between three states: TT, TR and RR. In order to find out which states bind non
      folded proteins, we measured the co-operativity in ATP hydrolysis by GroEL in the
      absence and presence of non-folded alpha-lactalbumin, under equilibrium
      conditions between GroEL and the non-folded protein. The non-folded protein is
      found to bind preferentially the T state of GroEL rings and to stimulate the
      ATPase activity of GroEL by (1) a direct effect on GroEL rings in the T state and
      (2) a shift in the equilibrium from the RR state toward the more active TR state.
      The coupling between co-operativity in ATP hydrolysis by GroEL and protein
      substrate binding and release by this molecular chaperone is shown.

PMID- 8568881
TI  - X-ray crystal structure of the two site-specific mutants Ile7Ser and Phe110Ser of
      azurin from Pseudomonas aeruginosa.
AB  - The blue copper protein azurin from Pseudomonas aeruginosa contains a single Trp
      residue that is believed to be involved in the inducible intramolecular electron
      transfer from a disulphide group to the copper centre. This residue shows in
      fluorescence spectra the highest energy emission of tryptophan-containing
      compounds at room temperature, which is explained by its rigid and highly
      hydrophobic environment. In order to investigate the role of the Trp residue in
      electron transfer and the influence of its environment, two mutations (17S and
      F110S) were introduced that were thought to increase the polarity and the
      mobility in its environment. The crystal structures of these mutants were solved
      at 2.2 A and 2.3 A resolution, respectively. These provide a structural basis for
      the changes observed in fluorescence spectra compared with the wild-type protein.
      We conclude from our results that these changes are not caused by a change in the
      dynamics of the Trp residue itself, but exclusively by an increased effective
      dielectric constant of the microenvironment of Trp48 and by changes in mobility
      of the mutated residues.

PMID- 8568882
TI  - Ion pairs significantly stabilize coiled-coils in the absence of electrolyte.
AB  - We have used a synthetic coiled-coil peptide model system to address the long
      perplexing issue as to why coiled-coils are in general more stable at acidic pH
      than at neutral pH. Contrary to the above expectation, our results show that at
      low ionic strength (10 mM) the coiled-coil was much more stable at neutral pH
      than at acidic pH against both thermal and urea unfolding, indicating that the
      Lys(+)-Glu- ions pairs present around the coiled-coil interface at neutral pH
      contribute significantly to the stability of the coiled-coil. However, while the
      addition of NaCl had no significant effect on the coiled-coil stability at
      neutral pH, its stability at acidic pH increased dramatically. The cross-over
      point between the stability at acidic pH and neutral pH occurred at around 100 mM
      salt, above which the coiled-coil became more stable at acidic pH, in agreement
      with published results. Therefore, salt effect, rather than intrinsic property,
      such as carboxyl-carboxyl hydrogen bonding, causes this coiled-coil to become
      more stable at acidic pH. The preferential stabilizing effect of salt on the
      coiled-coil at acidic pH can be best explained in terms of the condensation of
      anions to the positively charged groups on the coiled-coil, the net density of
      which increases as glutamic acid residues become protonated in acidic pH.

PMID- 8568883
TI  - Affinity selective isolation of ligands from peptide libraries through display on
      a lac repressor "headpiece dimer".
AB  - DNA binding by the Escherichia coli lac repressor is mediated by the
      approximately 60 amino acid residue 'headpiece' domain. The dimer of headpiece
      domains that binds to the lac operator is normally formed by association of the
      much larger approximately 300 amino acid residue C-terminal domain. We have used
      in vitro selection to isolate 'headpiece dimer' molecules containing two
      headpiece domains connected via a short peptide linker. These proteins bind
      plasmid molecules with sufficient stability to allow association of a peptide
      epitope displayed at the C terminus of the headpiece dimer with the plasmid
      encoding that peptide. Libraries of peptides displayed on the C terminus of a
      headpiece dimer can be screened for specific receptor ligands by affinity
      enrichment of peptide-headpiece dimer-plasmid complexes using an immobilized
      receptor. After each round of enrichment, transformation of E. coli with
      recovered plasmids permits amplification of the selected population. After
      several rounds of enrichment, sequencing of individual clones reveals the
      structure of the selected peptides. Headpiece dimer libraries allow selection of
      peptide ligands of higher average affinity than similar libraries based on the
      intact lac repressor. Interestingly, the presence of the lac operator is not
      required for plasmid binding by the headpiece dimer protein.

PMID- 8568884
TI  - Molecular characterization of the 71E late puff in Drosophila melanogaster
      reveals a family of novel genes.
AB  - Early metamorphic development in Drosophila melanogaster is initiated by pulses
      of the steroid hormone ecdysone, which are transduced into tissue-specific
      transcriptional cascades. This process begins with the hormone-dependent
      activation of a set of transcription factors (early genes) that, in turn,
      activate set of tissue-specific effector genes (late genes). The 71E cytogenetic
      region of the salivary gland polytene genome contains several ecdysone-regulated
      transcription units. Molecular techniques were used to analyze these genes, their
      transcriptional program and their evolutionary relatedness. We find that this
      region contains a cluster of ten coordinately regulated late genes (L71 genes)
      that are organized as five divergently transcribed gene pairs. Maximum parsimony
      analysis suggests that an ancestral L71 gene duplicated to form the first gene
      pair which was, in turn, duplicated to form the set of gene pairs. The L71 gene
      products form a family of small, chemically basic proteins with a conserved
      backbone of cysteine residues. In addition, the 71E region contains another gene
      (I71-1) with the regulatory and biochemical characteristics of the salivary gland
      intermolt glue proteins.

PMID- 8568885
TI  - Non-conservative mutations are well tolerated in the globular region of yeast
      histone H4.
AB  - Yeast histone H4 has been mutagenized at several positions which participate in
      the globular core of the nucleosome. The native protein contains residues at
      those positions which are invariant or highly conserved over all known H4
      sequences, whether from yeast, Tetrahymena or higher eukaryotes. Nonetheless the
      protein is tolerant of non-conservative mutations. At the level of cell function
      the mutant proteins cause no significant change in length of the cell cycle of
      mating efficiency. At the level of chromatin structure no effect is observed on
      the internucleosomal spacing of chromatin or the pattern of hydroxyl radical
      cleavage of nucleosomal DNA.

PMID- 8568886
TI  - Intron-encoded endonuclease I-TevII binds across the minor groove and induces two
      distinct conformational changes in its DNA substrate.
AB  - I-TevII is the homing endonuclease encoded by the sunY intron of bacteriophage
      T4. The enzyme cleaves an intronless sunY gene near the exon I-exon II junction,
      thereby initiating intron homing into its cognate intronless allele.
      Specifically, I-TevII cleaves its DNA target 13 to 15 nucleotides (nt) downstream
      of the sunY intron insertion site, generating 2-nl 3'-OH extensions. Here, we
      present evidence that I-TevII makes predominantly minor groove contacts in two
      regions of its recognition sequence, as does I-TevI, the other homing
      endonuclease encoded by phage T4. Following cleavage, I-TevII was shown to remain
      bound to one of its DNA products, suggesting possible additional roles for the
      endonuclease in the mobility process. Interestingly, two distinct conformational
      changes were detected by gel analysis in the DNA substrate following binding by I
      TevII, one occurring in the absence of Mg2+, the second being dependent on the
      presence of Mg2+. The Mg(2+)-induced distortion accompanies a nick in one strand,
      and may serve to bring the cleavage site on the other strand into proximity with
      the catalytic domain of the protein.

PMID- 8568887
TI  - Duplex destabilization in superhelical DNA is predicted to occur at specific
      transcriptional regulatory regions.
AB  - Analytic methods that accurately calculate the extent of duplex destabilization
      induced in each base-pair of a DNA molecule by superhelical stresses are used to
      analyze several genomic DNA sequences. Sites predicted to be susceptible to
      stress-induced duplex destabilization (SIDD) are found to be closely associated
      with specific transcriptional regulatory regions. Operators within the promoters
      of SOS-regulated Escherichia coli genes are destabilized by superhelical
      stresses, whereas closely related sequences present elsewhere on that genome are
      not. Analysis of genomic sequences from the budding yeast Saccharomyces
      cerevisiae finds a distinctive tripartite pattern, in which the 3' and 5' termini
      of genes are destabilized, but the sequence encoding the primary transcript is
      not. Three rDNA genes from higher eukaryotes exhibit a similar pattern.
      Implications of these results regarding possible mechanisms of activity of the
      regions involved are discussed. A strategy is presented for designing experiments
      in which the susceptibility to SIDD of a local region is altered without changing
      its local base sequence. The occurrence of the observed SIDD patterns provides a
      new approach to searching uncharacterized genomic sequences for transcriptionally
      active regions.

PMID- 8568888
TI  - The influence of single base changes on UV mutational activity at two
      translocated hotspots.
AB  - Mutation hotspots have been a staple of mutation spectra since the introduction
      of fine structure mutation mapping almost 40 years ago. It has been well
      established that sequence context is an important determinant of mutational
      activity at mutagen induced hotspots and coldspots. However, our understanding of
      the sequence effectors of base substitution hotspots is quite limited. This is
      because manipulation of the sequence about a hotspot site in a marker gene is
      restricted by the need to maintain a functional marker. In this work, we describe
      a generalizable system for studying sequence context effects on mutagenesis. We
      have prepared a variant of the supF tRNA gene (a marker used by us in previous
      studies) in which an eight-base palindrome, the site of two UV hotspots in the
      interior of the gene, was copied into the acceptor stem and pre-tRNA region. The
      variant tRNA was active. The UV mutation spectrum of this variant showed that the
      new copy of the palindrome generated two hotspots which were as intense as the
      original sites in the interior of the gene. Variant genes were constructed with
      all possible bases at the first position in the palindrome in the pre-tRNA
      sequence, which does not affect tRNA function. The mutation analysis showed that
      activity at one of the hotspots could be reduced or enhanced by the changes,
      while activity at the other site was not significantly affected. The base changes
      did not influence the frequency of cyclobutane dimer or (6-4) photoproduct
      formation at the two hotspot sites. Thus, the changes in mutational activity were
      due to the influence of sequence context on the efficiency of mutation formation
      at the sites of UV lesions.

PMID- 8568889
TI  - Microsecond rotational dynamics of actin: spectroscopic detection and theoretical
      simulation.
AB  - We have investigated the microsecond rotational dynamics of F-actin with
      transient phosphorescence anisotropy (TPA) spectroscopy, and analyzed the data to
      determine the relative contributions from rigid-body rotations and from
      intrafilament bending and twisting, using a theoretical model developed for DNA
      dynamics by Schurr and co-workers. The fits of the data to the model were
      constrained by independently determining the orientation of the dye's absorption
      dipole (by transient absorption anisotropy, TAA) and the actin filament length
      distribution (by electron microscopy). We conclude that (1) the Schurr theory
      enables calculation of the torsional flexibility of actin independent of any
      contribution from rigid body rotations of the whole filament, (2) the TPA decays
      cannot be explained by rigid-body or bending rotations, but reflect primary
      twisting motions within actin filaments, and (3) the dynamic properties of actin
      filaments are best ascribed to a continuous elasticity. This analysis establishes
      a firm methodological foundation for future studies of the effects or
      perturbations of the dynamics of actin on its functional properties.

PMID- 8568890
TI  - Geometry of the flagellar motor in the cytoplasmic membrane of Salmonella
      typhimurium as determined by stereo-photogrammetry of quick-freeze deep-etch
      replica images.
AB  - The precise geometry of the flagellar basal structure anchored in the cytoplasmic
      membrane was determined by digital stereo-photogrammetry of the images captured
      by quick-freeze deep-etch replica electron microscopy. In order to examine the
      structure on the periplasmic side of the membrane, we analyzed the MS ring
      complexes of Salmonella typhimurium overproduced in the cytoplasmic membrane of
      Escherichia coli. The rod, the S ring, and the shoulder of the M ring were
      exposed to the periplasm. On the cytoplasmic side of the membrane, small bumps
      corresponding to the cytoplasmic rod were discernible. We also examined the
      intact inner surface of the cells of polyhook mutant which was prepared by a new
      protocol and found the bell-shaped structure extending from the membrane towards
      the cytoplasm. It was identified as the C ring, since it was located at the base
      of the polyhook. Various dimensions of the MS ring complex and the C ring
      projecting from the membrane were determined by digital stereo-photogrammetry,
      and a three-dimensional model of the total basal structure is presented.

PMID- 8568891
TI  - Kinetics of sodium ion binding to DNA quadruplexes.
AB  - The binding environments of sodium ions on oligomeric DNA quadruplex structures
      have been examined by 23Na NMR. Competitive ion binding experiments confirm that
      the selectivity of univalent cations for the strong sites on the G-quadruplex
      d(G4T4G4) follows the order K+ > Na+ > Cs+. 23Na intensity measurements
      demonstrate a class of sodium ions that are not detectable by NMR, establishing
      that the sodium ions bind with loss of water of hydration. These measurements
      define the number of occupied, specific sodium ion binding sites per quadruplex
      as 2(+/- 1). In contrast to the rapid exchange of specifically bound sodium ions
      from the tetrameric G-quadruplex structure d(T2G4T), exchange from the dimeric G
      quadruplex structure of d(G4T4G4) is slow on the timescale of the 23Na NMR
      relaxation. 23Na NMR relaxation measurements, performed as a function of
      temperature, allow the kinetics of sodium ion complexation to be determined. The
      lifetime of specifically bound sodium ions is estimated as 180 microseconds at 20
      degrees C. The temperature dependence of the exchange rates suggests a fully
      hydrated transition state.

PMID- 8568892
TI  - The crystal structure of a high oxygen affinity species of haemoglobin (bar
      headed goose haemoglobin in the oxy form).
AB  - We have determined the crystal structure of bar-headed goose haemoglobin in the
      oxy form to a resolution of 2.0 A. The R-factor of the model is 19.8%. The
      structure is similar to human HbA, but contacts between the subunits show
      slightly altered packing of the tetramer. Bar-headed goose blood shows a greatly
      elevated oxygen affinity compared to closely related species of geese. This is
      apparently due to a single proline to alanine mutation at the alpha 1 beta 1
      interface which destabilises the T state of the protein. The beta chain N and C
      termini are well-localized, and together with other neighbouring basic groups
      they form a strongly positively charged groove at the entrance to the central
      cavity around the molecular dyad. The well-ordered conformation and the three
      dimensional distribution of positive charges clearly indicate this area to be the
      inositol pentaphosphate binding site of bird haemoglobins.

PMID- 8568893
TI  - Analysis of main chain torsion angles in proteins: prediction of NMR coupling
      constants for native and random coil conformations.
AB  - Using a data base of 85 high resolution protein crystal structures the
      distributions of main chain torsion angles, both in secondary structure and in
      coil regions where no secondary structure is present, have been analysed. These
      torsion angle distributions have been used to predict NMR homonuclear and
      heteronuclear coupling constants for residues in secondary structure using known
      Karplus relationships. For alpha helices, 3(10) helices and beta strands mean
      predicted 3JHN alpha coupling constants are 4.8, 5.6 and 8.5 Hz, respectively.
      These values differ significantly from those expected for the ideal phi angles
      (3.9, 3.0 and 8.9 Hz; phi = -57 degrees, -49 degrees, -139 degrees for alpha and
      3(10) helices and beta strands (antiparallel), respectively) in regular secondary
      structure, but agree well with available experimental NMR data for nine proteins.
      The crystallographic data set has also been used to provide a basis for
      interpreting coupling constants measured for peptides and denatured proteins.
      Using a model for a random coil, in which all residues adopt distributions of
      phi, psi angles equivalent to those seen for residues in the coil regions of
      native folded proteins, predicted 3JHN alpha values for different residue types
      have been found to range from 5.9 Hz and 6.1 Hz for glycine and alanine,
      respectively, to 7.7 Hz for valine. A good correlation has been found between the
      predicted 3JHN alpha coupling constants for this model and experimental values
      for a set of peptides that other evidence suggest are highly unstructured. For
      other peptides, however, deviations from the predictions of the model are clear
      and provide evidence for additional interactions within otherwise disordered
      states. The values of homonuclear and heteronuclear coupling constants derived
      from the protein data base listed here therefore provide a basis not only for
      analysing the secondary structure of native proteins in solution but for
      assessing and interpreting the extent of structure present in peptides and non
      native states of proteins.

PMID- 8568894
TI  - Conformational analysis of peptides corresponding to beta-hairpins and a beta
      sheet that represent the entire sequence of the alpha-spectrin SH3 domain.
AB  - In an attempt to identify potential folding initiation sites for a small, all
      beta-protein domain, we have examined the conformational preferences in aqueous
      solution of peptides that span the entire length of the alpha-spectrin SH3
      domain, using proton nuclear magnetic resonance (NMR) and circular dichroism (CD)
      spectroscopy. Two of the peptides correspond to beta-hairpins (m6 and m8), one to
      the RT-loop (m4, which can be considered as a distorted beta-hairpin), one to a
      beta-hairpin created by joining the N and C-terminal strands via a small linker
      (m2) and the fifth one to a three-stranded antiparallel beta-sheet composed of
      beta-hairpins m6 and m8 (m68). To estimate the distorting effect of the aromatic
      side-chains of Trp41 and Trp42 on the CD and NMR spectra of peptides m6, m8 and
      m68, we have also analyzed a short, ten-residue random-coil peptide containing
      residues 39 to 44 (mC). The CD and NMR results indicate that none of the peptides
      populates to a large extent a particular secondary structure conformation.
      However, careful anlaysis of the NMR data reveals that peptides m6, m8 and m68
      could adopt, to a small extent, native-like conformations, although in the case
      of peptide m68 there is also evidence of the presence of non-native helical
      conformations. Addition of 30% (v/v) 2,2,2-trifluoroethanol stabilizes the
      appearance of non-native helical populations in some small regions of peptides
      m2, m4, m8 and m68, while it induces a native-like conformation in peptide m6.
      Those fragments corresponding to the two real beta-hairpins in the protein are
      the ones which exhibit some tendency to populate native-like structures (m6 and
      m8), while the ones corresponding to the long RT-loop (m4) or the newly created
      one (m2) are mainly unstructured in water solution. Although there could be some
      local interactions that favor the acquisition of a native secondary structure in
      this domain, tertiary interactions should play a major role in defining its
      native secondary structure.

PMID- 8568895
TI  - Entropy in bi-substrate enzymes: proposed role of an alternate site in
      chaperoning substrate into, and products out of, thymidylate synthase.
AB  - Three steps along the pathway of binding, orientation of substrates and release
      of products are revealed by X-ray crystallographic structures of ternary
      complexes of the wild-type Lactobacillus casei thymidylate synthase enzyme. Each
      complex was formed by diffusion of either the cofactor 5,10-methylene-5,6,7,8
      tetrahydrofolate or the folate analog 10-propargyl-5,8-dideazafolate into binary
      co-crystals of thymidylate synthase with 2'-deoxyuridine-5'-monophosphate. A two
      substrate/enzyme complex is formed where the substrates remain unaltered. The
      imidazolidine ring is unopened and the pterin of the 5,10-methylene-5,6,7,8
      tetrahydrofolate cofactor binds at an unproductive "alternate" site. We propose
      that the presence of the pterin at this site may represent an initial interaction
      with the enzyme that precedes all catalytic events. The structure of the 2'
      deoxyuridine-5'-monophosphate and 10-propargyl-5,8-dideazafolate folate analog
      complex identifies both ligands in orientations favorable for the initiation of
      catalysis and resembles the productive complex. A product complex where the
      ligands have been converted into products of the thymidylate synthase reaction
      within the crystal, 2'-deoxythymidine-5'-monophosphate and 7,8-dihydrofolate,
      shows how ligands are situated within the enzyme after catalysis and on the way
      to product release.

PMID- 8568896
TI  - Principles of helix-helix packing in proteins: the helical lattice superposition
      model.
AB  - The geometry of helix-helix packing in globular proteins is comprehensively
      analysed within the model of the superposition of two helix lattices which result
      from unrolling the helix cylinders onto a plane containing points representing
      each residue. The requirements for the helix geometry (the radius R, the twist
      angle omega and the rise per residue delta) under perfect match of the lattices
      are studied through a consistent mathematical model that allows consideration of
      all possible associations of all helix types (alpha-, pi- and 3(10)). The
      corresponding equations have three well-separated solutions for the interhelical
      packing angle, omega, as a function of the helix geometric parameters allowing
      optimal packing. The resulting functional relations also show unexpected
      behaviour. For a typically observed alpha-helix (omega = 99.1 degrees, delta =
      1.45 A), the three optimal packing angles are omega a,b,c = -37.1 degrees, -97.4
      degrees and +22.0 degrees with a periodicity of 180 degrees and respective helix
      radii Ra,b,c = 3.0 A, 3.5 A and 4.3 A. However, the resulting radii are very
      sensitive to variations in the twist angle omega. At omega triple = 96.9 degrees,
      all three solutions yield identical radii at delta = 1.45 A where Rtriple = 3.46
      A. This radius is close to that of a poly(Ala) helix, indicating a great packing
      flexibility when alanine is involved in the packing core, and omega triple is
      close to the mean observed twist angle. In contrast, the variety of possible
      theoretical solutions is limited for the other two helix types. Besides the
      perfect matches, novel suboptimal "knobs into holes" hydrophobic packing patterns
      as a function of the helix radius are described. Alternative "knobs onto knobs"
      and mixed models can be applied in cases where salt bridges, hydrogen bonds,
      disulphide bonds and tight hydrophobic head-to-head contacts are involved in
      helix-helix associations. An analysis of the experimentally observed packings in
      proteins confirmed the conclusions of the theoretical model. Nonetheless, the
      observed alpha-helix packings showed deviations from the 180 degrees periodicity
      expected from the model. An investigation of the actual three-dimensional
      geometry of helix-helix packing revealed an explanation for the observed
      discrepancies where a decisive role was assigned to the defined orientation of
      the C alpha-C beta vectors of the side-chains. As predicted form the model,
      helices with different radii (differently sized side-chains in the packing core)
      were observed to utilize different packing cells (packing patterns). In agreement
      with the coincidence between Rtriple and the radius of a poly(Ala) helix, Ala was
      observed to show greatest propensity to build the packing core. The application
      of the helix lattice superposition model suggests that the packing of amino acid
      residues is best described by a "knobs into holes" scheme rather than "ridges
      into grooves". The various specific packing modes made salient by the model
      should be useful in protein engineering and design.

PMID- 8568897
TI  - Direct measurement of the association of a protein with a family of membrane
      receptors.
AB  - A specific receptor is a requirement for most protein toxins and OmpF, a trimeric
      porin, was previously considered to be the unique membrane-receptor for colicin
      N. We show by qualitative in vivo analysis that the related porins OmpC or PhoE
      act as much less effective receptors. To elucidate receptor function, the in
      vitro binding of the 42 kDa toxin to each of the 120 kDa porin trimers was
      determined quantitatively using isothermal titration calorimetry. Colicin N binds
      to OmpF with Ka approximately 5 x 10(5) M-1 and a stoichiometry consistent with
      about three per trimer but it also binds to PhoE and OmpC with surprisingly
      similar affinities and stoichiometry. However, thermodynamic analysis of these
      hitherto unmeasured interactions suggests an unexpected entropic difference
      between these protein import receptors.

PMID- 8568898
TI  - Structural analysis of mitochondrial DNA molecules from fungi and plants using
      moving pictures and pulsed-field gel electrophoresis.
AB  - The size and structure of mitochondrial DNA (mtDNA) molecules was investigated by
      conventional and pulsed-field gel electrophoresis (PFGE) and by analyzing moving
      pictures during electrophoresis of individual fluorescently labelled mtDNA
      molecules. Little or no mtDNA that migrated into the gel was found in circular
      form for fungi (Schizosaccharomyces pombe, Saccharomyces cerevisiae and
      Neurospora crassa) or plants (Brassica hirta, tobacco, voodoo lily and maize).
      Most mtDNA migrated as a smear of linear DNA sizes from about 50 to 100 or 250
      kilobases (kb), depending on the species, irrespective of the size of the
      mitochondrial genome over a range of 0.06 to 570 kb. S. cerevisiae, B. hirta and
      tobacco also yielded a linear mtDNA fraction containing molecules > 1000 kb in
      size. About half the mtDNA remained in the well of the gel after PFGE. Moving
      pictures revealed that this well-bound (wb) mtDNA contained molecules larger than
      the genome size in linear form for all species (except N. crassa) and in multi
      fibered, comet-like forms for most of the wb mtDNA of N. crassa and Sc. pombe. A
      minor amount of the wb mtDNA with visually interpretable structure was circular:
      circle sizes were both larger and smaller than the 80-kb genome of S. cerevisiae,
      larger than the 19-kb genome of Sc. pombe and smaller than the 208-kb and 570-kb
      genomes of B. hirta and maize, respectively. About 25 to 75% of the wb mtDNA from
      cultured tobacco cells was found in circles smaller than its genome size. Partial
      digestion of Sc. pombe mtDNA with restriction endonucleases that cleave once per
      genome revealed gel bands at about 38 kb and 19 kb with a smear of sizes between
      the bands and below the 19-kb band, suggesting a head-to-tail genomic concatemer
      as the most prominent form in extracted mtDNA. A pattern of bands with smears was
      also found for complete digests (with multiply cleaving enzymes) of mtDNA from
      Sc. pombe, S. cerevisiae and N. crassa, but bands without smears were found for
      digests of DNA from phage lambda and several plasmids.

PMID- 8568899
TI  - An approach to random mutagenesis of DNA using mixtures of triphosphate
      derivatives of nucleoside analogues.
AB  - We describe a new method for random mutagenesis of DNA based on the use of a
      mixture of triphosphates of nucleoside analogues. The method relies on DNA
      amplification in vitro with Taq polymerase and in the presence of the 5'
      triphosphates of 6-(2-deoxy-beta-D-ribofuranosyl)-3,4-dihydro-8H-pyrimido-[4,5-C]
      [1,2]oxazin-7-one(dP) and of 8-oxo-2' deoxyguanosine (8-oxodG). The newly
      synthesised triphosphate derivative of dP (dPTP) is an excellent substrate for
      Taq polymerase (Km = 22 microM versus Km = 9.5 microM for TTP); it is
      incorporated in place of TTP and, with a approximately fourfold lower efficiency,
      in place of dCTP. After 30 cycles of DNA amplification, equimolar mixtures of the
      four normal dNTPs and dPTP yield the following frequencies of the four transition
      mutations: A-->G (4.4 x 10(-2), T-->C (4.3 x 10(-2), G-->A (1.1 x 10(-2) and C-
      >T (1.0 x 10(-2). The triphosphate derivative of 8-oxodG (8-oxodGTP) is
      incorporated opposite template adenine and yields two transition mutations (A-->C
      and T-->G) at frequencies of 0.8 x 10(-2) and 1.2 x 10(-2) respectively. Reaction
      mixtures containing dPTP and 8-oxodGTP results in both dP and 8-oxodG-induced
      mutations and an extensive array of codon changes in the absence of insertions
      and deletions. The method described differs from previous mutagenesis procedures
      in three respects: (1) it enables very high frequencies of base substitutions (up
      to 1.9 x 10(-1) (2) it allows control of the mutational load via the number of
      DNA amplification cycles and (3) it yields both transition and transversion
      mutations. The procedure may find application in the generation of libraries of
      DNA and protein mutants from which species with improved or novel activities may
      be selected.

PMID- 8568900
TI  - The elastic I-band region of titin is assembled in a "modular" fashion by weakly
      interacting Ig-like domains.
AB  - The vertebrate striated muscle protein titin is thought to play a critical role
      in myofibril assembly and passive tension. The recently determined complete
      primary structure of titin revealed a modular architecture that opens the way to
      a structural characterisation and the understanding of essential properties of
      this molecule through dissection into units that are structurally and/or
      functionally relevant. To understand the assembly process of titin, and
      ultimately the molecular basis of its elastic behaviour, we studied the
      thermodynamic properties of module pairs, the smallest structural unit that
      includes a module-module interface. Thus, selected module pairs and their
      component single modules from the I-band part of the titin molecule were
      expressed in Escherichia coli and their heat-induced and denaturant-induced
      unfolding was investigated with a combination of techniques (circular dichroism,
      fluorescence spectroscopy and nuclear magnetic resonance). The stabilities of
      single modules and pairs were determined from denaturation experiments. The
      module interface was also modelled on the basis of the sequence alignment of all
      approximately 40 immunoglobulin like modules from the I-band and the known
      structure of one of them. Our results show that all modules and module pairs
      examined are independently folded in solution. When covalently linked, although
      weakly interacting, they still behave as autonomous co-operative units upon
      unfolding. These observations lead us to suggest that folding of titin in vitro
      is a hierarchical event and that weak interactions between its adjacent modules
      must only partly account for its presumed elastic function.

PMID- 8568901
TI  - Crystal structure of an anti-anti-idiotype shows it to be self-complementary.
AB  - The structure of the Fab fragment of the mouse anti-anti-idiotypic monoclonal
      antibody (mAb) GH1002 was solved by X-ray crystallography. mAb GH1002 was
      elicited with the syngeneic anti-idiotype mAb MK2-23 which mimics the determinant
      defined by anti-human high molecular weight-melanoma associated antigen (HMW-MAA)
      mAb 763.74. The Fab fragments of mAb GH1002 exist in the crystal as dimers
      related by crystallographic 2-fold axes. The interface between dyad-related Fab
      fragments is formed primarily by interaction of the hypervariable loops of one
      with the other. The self-interaction of Fab fragments of anti-anti-idiotypic mAb
      GH1002 through their combining sites is extremely tight and intricate, closely
      resembling that observed in structures of id-anti-id complexes, and comparable in
      terms of total contact area, charge complementarity, and number of hydrogen
      bonds. The self-complementarity of the antibody observed here could be
      coincidental and thus reflect some non-specific binding capability. It might, on
      the other hand, be immunologically relevant and exemplify a certain degree of
      evolved self complementarity characteristic of antibodies participating in
      idiotypic cascades.

PMID- 8568902
TI  - Functional significance of loops in the receptor binding domain of Bacillus
      thuringiensis CryIIIA delta-endotoxin.
AB  - Analysis of the three surface loops in domain II of Bacillus thuringiensis
      CryIIIA delta-endotoxin has been carried out to assess their role in receptor
      binding and toxicity. Site-directed mutagenesis was used to convert loop residues
      to alanine and the mutant proteins were analyzed for structural stability,
      toxicity to beetle larvae (Tenebrio molitor), binding to receptors on T. molitor
      brush border membrane vesicles (Tm-BBMV) and insertion into BBMV, as measured by
      irreversible membrane receptor binding. This study demonstrates the functional
      significance of loops for binding and insertion. Alanine replacements in loop I
      resulted in disruption of receptor binding or structural instability. The double
      mutation, Y350A, Y351A, could be suppressed by replacing a nearby R345 with
      alanine, and the resultant mutant protein also showed reduced receptor binding.
      Substitution of N353 and D354 in loop I with alanine residues caused the loss of
      binding ability and toxicity. A loop II double mutant, P412A, S413A, had no
      effect on binding or toxicity. A block mutation of loop III residues to alanine
      had the effect of reducing receptor binding while concomitantly increasing
      toxicity by 2.4-fold. We compared this up-mutant to wild-type toxin in each step
      of physiological processing of protoxin: solubility, proteolytic activation, and
      insertion into the Tm-BBMV. The loop III block mutant showed increased membrane
      insertion, but was similar to wild-type toxin in other parameters. These results
      reveal that loop I and loop III in domain II of CryIIIA delta-endotoxin are
      involved in receptor binding. In addition, the direct correlation between
      toxicity and irreversible binding of the loop III block mutant (despite the
      indirect relationship to reversible binding) suggests that loop III may play a
      role in membrane insertion.

PMID- 8568903
TI  - Global optimum protein threading with gapped alignment and empirical pair score
      functions.
AB  - We describe a branch-and-bound search algorithm for finding the exact global
      optimum gapped sequence-structure alignment ("threading") between a protein
      sequence and a protein core or structural model, using an arbitrary amino acid
      pair score function (e.g. contact potentials, knowledge-based potentials,
      potentials of mean force, etc.). The search method imposes minimal conditions on
      how structural environments are defined or the form of the score function, and
      allows arbitrary sequence-specific functions for scoring loops and active site
      residues. Consequently the search method can be used with many different score
      functions and threading methodologies; this paper illustrates five from the
      literature. On a desktop workstation running LISP, we have found the global
      optimum protein sequence-structure alignment in NP-hard search spaces as large as
      9.6 x 10(31), at rates ranging as high as 6.8 x 10(28) equivalent threadings per
      second (most of which are pruned before they ever are examined explicitly).
      Continuing the procedure past the global optimum enumerates successive candidate
      threadings in monotonically increasing score order. We give efficient algorithms
      for search space size, uniform random sampling, segment placement probabilities,
      mean, standard deviation and partition function. The method should prove useful
      for structure prediction, as well as for critical evaluation of new pair score
      functions.

PMID- 8568904
TI  - Ultrastructural organization of avian stratum corneum lipids as the basis for
      facultative cutaneous waterproofing.
AB  - The ultrastructure of naked neck epidermis from the ostrich (Struthio camelus)
      and ventral apterium from watered, and water-deprived, Zebra finches (Taeniopygia
      [Poephila] guttata castanotis) is presented. The form and distribution of the
      fully differentiated products of the lipid-enriched multigranular bodies are
      compared in biopsies post-fixed with osmium tetroxide or ruthenium tetroxide. The
      fine structure of ostrich epidermis suggests it is a relatively poor barrier to
      cutaneous water loss (CWL). The fine structure from watered, and 16-hr water
      deprived Zebra finches, considered in conjunction with measurements of CWL,
      confirms previous reports of "facultative waterproofing," and emphasizes the
      rapidity of tissue response to dehydration. The seemingly counterintuitive facts
      that one xerophilic avian species, the ostrich, lacks a "good barrier" to CWL,
      whereas another, the Zebra finch, is capable of forming a good barrier, but does
      not always express this capability, are discussed. An explanation of these data
      in comparison to mammals centers on the dual roles of the integument of
      homeotherms in thermoregulation and conserving body water. It is concluded that
      birds, whose homeothermic control depends so much on CWL, cannot possess a
      permanent "good barrier," as such would compromise the heat loss mechanism.
      Facultative waterproofing (also documented in lizards) protects the organism
      against sudden reductions in water availability. In birds, and probably in snakes
      and lizards, facultative waterproofing involves qualitative changes in epidermal
      cell differentiation. Possible control mechanisms are discussed.

PMID- 8568905
TI  - Histological features of endomysium, perimysium and epimysium in rat lateral
      pterygoid muscle.
AB  - The distribution of the endomysium, perimysium, and epimysium and their
      constituent connective tissue fiber types in the mature rat lateral pterygoid
      muscle was examined with the light microscope. The endomysium and perimysium were
      relatively thin and consisted mainly of reticular fibers. The epimysium was
      thicker than the intramuscular sheaths and consisted of both collagen and
      reticular fibers; however, the thickness and constitutent connective tissue fiber
      types of these sheaths varied regionally. Near the articular capsule and disc,
      the endomysium, perimysium, and epimysium were all thicker than in other regions
      of the muscle and consisted of collagen, reticular, and elastic fibers. The
      perimysium bound the bundles of muscle fibers together and frequently included
      blood vessels and nerves. As the superior head of the pterygoid muscle approached
      its insertion, sheaths of perimysium divided this head into smaller and smaller
      bundles of muscle fibers. In the inferior head, some of the perimysial sheaths
      and part of the epimysium were aponeurotic, and many muscle fibers attached to
      them. There were few such aponeurotic regions in the superior head.

PMID- 8568906
TI  - Motor pool organization of the external gastrocnemius muscle in the turtle,
      Pseudemys (Trachemys) scripta elegans.
AB  - The spinal cord of the adult turtle, Pseudemys (Trachemys) scripta elegans, is
      now considered a promising model for the study of the segmental motor system in
      the generalized tetrapod. To facilitate such studies we have examined the
      location, soma geometry, soma size, and number of motoneurons innervating the
      external gastrocnemius (EG) muscle in this species, as this muscle is ideally
      suited to the study of interrelations between the neuronal and muscular
      components of the segmental motor system. Motoneurons were retrogradely labeled
      following application of horseradish peroxidase to the EG muscle nerve. In both
      horizontal and transverse planes, labeled motoneurons innervating the EG muscle
      were concentrated in the S1 lumbosacral segment, and extended rostrally and
      caudally as far as the exists of the D10 and S2 spinal nerves, respectively. In
      the transverse plane, motoneurons were arranged in a longitudinal column which
      occupied the dorsolateral quadrant of the ventral horn. EG motoneurons are
      fusiform in shape and present their largest dimension in the transverse plane
      with their long axis oriented in the ventromedial to dorsolateral plane. The soma
      diameters of EG motoneurons were normally distributed, reflecting the absence of
      separate fusimotor innervation in reptilian species. In individual turtles, there
      was a two- to threefold range in soma diameter while soma surface area extended
      over a seven- to tenfold range. Based on cell counts from five animals, the EG
      motor pool was composed of approximately 75 motoneurons. Taken together, the
      results of this study provide valuable information for interpreting the results
      of future studies on the segmental motor system of this species under both normal
      and pathophysiological conditions.

PMID- 8568907
TI  - Light microscopic detection of sugar residues in rabbit embryo teeth with lectin
      horseradish peroxidase conjugates.
AB  - We investigated the binding of five HRP-conjugated lectins to rabbit tooth germs
      at the cap and late bell stages of development. The results revealed some changes
      in the glycosylation patterns of the glycoconjugates. Sugar residues, such as
      alpha-D-mannose, methyl-D-glucose, N-acetylglucosamine, beta-D-galactosamine, D
      galactose, and sialic acid, were detectable in some components of the tooth
      germs. The most conspicuous developmental change was increased binding of Con A
      and WGA. These lectins showed, at the cap stage, moderate binding to the (pre)
      ameloblasts and (pre)-odontoblasts. With further development to the late bell
      stage, but prior to the achievement of well-defined morphological-functional
      characteristics, the odontoblasts and ameloblasts displayed considerable amounts
      of alpha-D-mannose, alpha-D-glucose as well as beta-D-acetylglucosamine and
      sialic acid. Appropriate control studies confirmed the specificity of the binding
      of the lectins. Two lectins (DBA and PNA) with known specificity for N
      acetylgalactosamine groups were bound by the basement membranes in tooth germs at
      the cap stage. A third lectin (RCA) with the same specificity did not produce any
      detectable staining in the same material. Further studies must be planned to
      determine the specific functions and significance of lectin-HRP-binding
      glycoconjugates in odontogenesis.

PMID- 8568908
TI  - Surface morphology of basilar papilla of the tufted duck Aythya fuligula, and
      domestic chicken Gallus gallus domesticus.
AB  - Quantitative details of the surface morphology of the hearing organ, the Papilla
      basilaris, as seen in the scanning electron microscope are described for the
      tufted duck Aythya fuligula and for comparison for the domestic chicken Gallus
      gallus domesticus, for which some published information is already available. As
      in the other avian species investigated to date, each papilla shows a unique
      constellation of features. The papilla of the tufted duck is 3.5 mm long in the
      unfixed state and contains 8,200 sensory hair cells. It shows systematic changes
      in its surface features along the length and across the width of the sensory
      epithelium. In general, its features and those of the chicken Papilla basilaris
      can be described as relatively primitive in comparison with other species. The
      tufted duck papilla does, however, show one feature that has so far been found to
      be well developed only in advanced papillae; the number of stereovilli per hair
      cell bundle is generally much higher on hair cells of the neural than those on
      the abneural side. This difference is only weakly developed in the chicken. It is
      clear that features considered to be evolutionarily advanced were acquired
      independently of one another during evolution and that each bird species can show
      a mosaic of primitive and advanced features.

PMID- 8568909
TI  - Role of rat strain in the differential sensitivity to pharmaceutical agents and
      naturally occurring substances.
AB  - The development of drugs to combat diseases, chemicals to improve food
      production, or compounds to enhance the quality of life necessitates, by law, the
      use of laboratory animals to test their safety. In order to simulate the human
      condition it is necessary to choose a species in which pharmacokinetic and
      toxicokinetic mechanisms are established and resemble those of humans. The
      advantages of the use of the rat in drug and chemical toxicity testing include
      (a) metabolic pathway similarities to humans; (b) numerous similar anatomical and
      physiological characteristics; (c) a large database, which is extremely important
      for comparative purposes; and (d) the ease of breeding and maintenance of animals
      at relatively low cost. However, the choice of rat can be complicated, especially
      when over 200 different strains of rat are known to exist. The aim of this review
      is to summarize genetically determined differences in the responsiveness of rat
      strains to drugs and naturally occurring chemicals and to show that
      susceptibility is dependent on the target organ sensitivities, which may also be
      strain dependent. It is suggested that detailed studies of strain differences may
      help to clarify toxic mechanisms. Such studies are usually best conducted using
      inbred strains in which the genetic characteristics have been fixed, rather than
      in outbred stocks in which individual samples of animals may differ, the
      phenotype is variable, and the stocks are subject to substantial genetic drift.
      The fact that strains may differ also needs to be taken into account in assessing
      the potential hazard of the chemical, particularly when a study involves only a
      single strain and therefore provides no assessment of likely strain variation.

PMID- 8568910
TI  - Human exposure to naturally occurring hydroquinone.
AB  - Hydroquinone (HQ) is a nonvolatile chemical used in the photographic, rubber,
      chemical, and cosmetic industries. HQ is also known to occur in nature as the
      beta-D-glucopyranoside conjugate (arbutin), and free HQ is a known component of
      cigarette smoke. Low concentrations of HQ have been detected in the urine and
      plasma of humans with no occupational or other known exposure to HQ. The studies
      reported here investigate dietary and other potential sources of HQ and their
      contribution to HQ concentrations in the plasma and urine of human volunteers.
      Analysis of possible food sources of HQ by GC indicated significant amounts of
      arbutin in wheat products (1-10 ppm), pears (4-15 ppm), and coffee and tea (0.1
      ppm). Free HQ was found in coffee (0.2 ppm), red wine (0.5 ppm), wheat cereals
      (0.2-0.4 ppm), and broccoli (0.1 ppm). After consuming a meal including arbutin-
      and HQ-containing foods, volunteers showed significant increases in plasma and
      urinary levels of HQ and its conjugated metabolites (total HQ). Mean plasma
      concentrations of total HQ peaked at 5 times background levels at 2 h after the
      completion of the meal, and mean urinary excretion rates of total HQ peaked at 12
      times background at 2-3 h after the meal. Immediately after smoking four
      cigarettes in approximately 30 min, mean plasma concentrations of total HQ were
      maximally 1.5 times background levels; mean urinary excretion rates of total HQ
      peaked at 2.5 times background at 1-3 h after smoking. These data indicate that
      considerable human exposure to HQ can result from plant-derived dietary sources
      and, to a lesser extent, from cigarette smoke.

PMID- 8568911
TI  - Evaluation of the toxicological risk to humans of caulerpenyne using human
      hematopoietic progenitors, melanocytes, and keratinocytes in culture.
AB  - The extensive growth of Caulerpa taxifolia in the Mediterranean sea produces
      important quantities of bioactive secondary metabolites unable to enter the food
      chain. The cytotoxic effects of caulerpenyne, the major secondary metabolite from
      C. taxifolia, was studied in different in vitro models: skin cells, primary
      cultures of melanocytes and keratinocytes, immortalized keratinocytes (HaCaT and
      HESV), and bone marrow cells (hematopoietic progenitors CFU-GM). Typical dose
      response curves from neutral red uptake and MTT assays were recorded in all
      models with IC50 ranging from 6 to 24 microM. Hematopoietic progenitors were more
      sensitive to caulerpenyne than melanocyte and keratinocyte cell lines, which
      could be due to their higher proliferative rate. The distribution of aggregates
      in colonies, macroclusters, and microclusters of hematopoietic progenitors was
      also altered in the presence of caulerpenyne. From our evaluation of the
      caulerpenyne concentrations required to result in cellular toxicity, the risks of
      cutaneous and/or food intoxication to humans may be considered minimal.

PMID- 8568913
TI  - Light catalytically cracked naphtha: subchronic toxicity of vapors in rats and
      mice and developmental toxicity screen in rats.
AB  - Both a subchronic inhalation study and a developmental toxicity screen were
      performed with vapors of light catalytically cracked naphtha (LCCN). In the
      subchronic study, four groups of mice and rats (10 animals per sex per species)
      were exposed for approximately 13 wk (6 h/d, 5 d/wk) to concentrations of LCCN
      vapors of 0, 530, 2060, or 7690 mg/m3. An untreated control group was also
      included. Animals were observed daily and body weights were taken weekly. No
      significant treatment-related changes were found in clinical signs, body weight,
      serum chemistry, hematology, histopathology of 24 tissues, or weights of 12
      organs. A marginal decrease was noted in the number of sperm per gram of
      epididymis. In the developmental toxicity screen, presumed-pregnant Sprague
      Dawley rats were exposed to 0, 2150, or 7660 mg/m3 of LCCN vapors, 6 h/d on d 0
      19 of gestation. Females were sacrificed on d 20; dams and fetuses were examined
      grossly and fetuses were later evaluated for skeletal and visceral effects. The
      number of resorptions was increased by approximately 140% in the group receiving
      7660 mg/m3; no other definite treatment-related changes were observed. Overall,
      the effects of exposure to partially vaporized LCCN were minimal.

PMID- 8568912
TI  - Generation of reactive oxygen species by Co(II) from H2O2 in the presence of
      chelators in relation to DNA damage and 2'-deoxyguanosine hydroxylation.
AB  - The generation of reactive oxygen species by Co(II) from H2O2 in the presence of
      chelators and related DNA damage was investigated by electron spin resonance
      (ESR), electrophoretic assays, and high-performance liquid chromatography (HPLC).
      Incubation of Co(II) with beta-alanyl-3-methyl-L-histidine (anserine) and H2O2
      generated .OH radicals. Omission of any one component sharply reduced the amount
      of .OH radicals generated, indicating that anserine modulated the oxidation
      potential of Co(II) to enhance its capability to generate .OH radicals from H2O2.
      Formate only moderately decreased the .OH radical generation, while ethanol had
      no observable effect, indicating that the generation of .OH radical is site
      specific. The metal ion chelator 1,10-phenanthroline reduced the .OH radical
      generation, and deferoxamine suppressed it with the formation of deferoxamine
      nitroxide radical. Electrophoretic assays using both lambda Hind III linear DNA
      and PM2 supercoiled DNA showed that .OH radicals generated from a mixture of
      Co(II), H2O2, and anserine caused DNA strand breaks. A mixture of Co(II), H2O2,
      and 1,10-phenanthroline also caused DNA strand breaks, which were inhibited by
      sodium azide, indicating that 1O2 was involved in DNA damage. HPLC measurements
      showed that .OH radicals and 1O2 generated by Co(II) reactions caused 2'
      deoxyguanosine hydroxylation to form 8-hydroxy-2'-deoxyguanosine. ESR spin
      trapping measurements provided evidence for 1O2 generation by Co(II) from H2O2 in
      the presence of 1,10-phenanthroline. The results indicate that the oxidation
      potential of Co(II) can be modulated by chelators to facilitate its generation of
      reactive oxygen species from H2O2. These species may be involved in Co(II)
      induced cellular damage.

PMID- 8568914
TI  - Characteristics of the acute-phase pulmonary response to silica in rats.
AB  - Exposure to silica, a cytotoxic and fibrogenic mineral dust, has been
      demonstrated to cause pulmonary inflammation and damage to the lung tissue. In
      contrast to the long-term consequences, little information exists on the sequence
      of inflammatory/damaging events occurring acutely after exposure to silica. The
      purpose of this study was to determine the minimum time after the administration
      of silica that the inflammatory/damage response is detectable and the temporal
      relationship of these processes. Male Fischer 344 rats were dosed intratracheally
      with silica (2.5 or 10 mg/100 g body weight) or saline vehicle. At 2 and 4 h
      after instillation, both cellular (total cell count and neutrophil count) and
      biochemical (total protein, albumin, and beta-glucuronidase and lactate
      dehydrogenase activities) parameters of inflammation and damage were evaluated in
      the bronchoalveolar lavage fluid. At 2 h, total protein levels were elevated at
      both silica doses, but all other parameters were unchanged; however, 4 h after
      silica exposure all parameters were elevated over those of the saline control. In
      a further attempt to characterize the inflammatory/damage processes, luminol
      dependent chemiluminescence (LDCL) was performed on aliquots of chopped lung. At
      2 h after silica instillation, phorbol myristate acetate-stimulated lung tissue
      from silica-treated rats had no increase in light production when compared to
      controls, whereas after 4 h there were significant increases in LDCL activity in
      both dose groups when compared to controls. The addition of superoxide dismutase
      (SOD) decreased LDCL activity of the 2.5 mg/100 g group by 59% (2 h) and 66% (4
      h), and of the 10 mg/100 g group by 49% (2 h) and 73% (4 h). Alternatively, the
      addition of N-omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of
      nitric oxide synthase, decreased the 2.5 mg/100 g group by 52% (2 h) and 60% (4
      h). The 10 mg/100 g group was decreased by 67% (2 h), but only exhibited a 12%
      reduction at 4 h. SOD and L-NAME also inhibited the background LDCL in saline
      treated rats. These reductions in LDCL activity indicate that reactive oxygen and
      nitrogen species play a role in the acute phase pulmonary response from silica.
      The results of this study indicate that the initial stages of damage begin to
      appear by 2 h, but damage and inflammation are definitive by 4 h after
      administration of silica in rats.

PMID- 8568915
TI  - Control of neuronal morphology in vitro: interplay between adhesive substrate
      forces and molecular instruction.
AB  - Among the factors which influence neuronal morphology, the degree of substrate
      adhesivity has been suggested to play an important role in the growth and
      guidance of neurites. The present study was undertaken to investigate apparently
      contradictory results relating substrate adhesivity to the extent of neurite
      outgrowth. By using substrates coated with different concentrations of
      polyornithine to vary adhesivity, we could show that intermediate levels of
      neuron-to-substrate adhesive strength favored neurite outgrowth more than
      substrates of high or low adhesivity. However, when neurons were plated on
      substrates derived from the extracellular matrix, the strength of neuron-to
      substrate adhesion was important for the growth of dendrite-like minor neurites,
      but not for the extension of axon-like major neurites, which grew independently
      of adhesive forces. On substrates of the cell adhesion molecule L1, growth of
      both major and minor neurites was adhesion-independent. Finally, in the presence
      of tenascin added to the culture medium, neurite growth was inhibited
      irrespective of the adhesivity of the substrate and the presence of substrate
      bound extracellular matrix molecules or L1. These observations suggest that
      intermediate forces of adhesivity favor neurite growth in general, but that
      purely adhesive forces can be dominated by specific molecular instructions which
      differentially affect growth of major and minor neurites in positive and negative
      ways.

PMID- 8568916
TI  - Differentially expressed genes after peripheral nerve injury.
AB  - In an attempt to identify genes associated with Wallerian degeneration and
      peripheral nerve regeneration we have performed differential hybridization
      screening of a cDNA library from crushed rat sciatic nerve (7 days postlesion)
      using radioactively labeled cDNA prepared from poly(A)+ RNA of normal vs. crushed
      nerve. Screening of 5,000 randomly selected colonies yielded 24 distinct clones
      that were regulated following nerve injury. Fifteen of the differentially
      expressed sequences could be classified as induced, whereas 9 sequences appeared
      to be repressed at 1 week postcrush. Sequencing and computer-assisted sequence
      comparison revealed 3 classes of regulated cDNA clones representing 1) novel gene
      sequences (8 clones) including 3 transcripts containing a repetitive "brain
      identifier" (ID) element; 2) identified genes (7 clones) with previously
      undetected expression in the peripheral nervous system (PNS), such as
      apolipoprotein D, peripheral myelin protein 22kD (PMP22), SPARC (secreted
      protein, acidic and rich in cysteine), sulfated glycoprotein SGP-1, apoferritin,
      decorin, and X16/SRp20; and 3) identified genes (9 clones) with known expression
      in the PNS including, e.g., the myelin protein P0, gamma-actin, vimentin, alpha
      tubulin, chargerin II, and cytochrome c-oxidase subunit I. Northern blot and
      polymerase chain reaction analyses with RNA from crushed and transected nerve
      demonstrated that sequences with related function, like the group of myelin
      genes, cytoskeleton genes, genes involved in RNA processing and translation, in
      lipid transport or energy metabolism showed closely related temporal patterns of
      expression during nerve degeneration and regeneration. Finally, we compared the
      differentially expressed genes identified at 7 days after crush injury (this
      investigation) with the regulated sequences isolated previously by De Leon et al.
      (J Neurosci Res 29:437-488, 1991) from a 3 day postcrush sciatic nerve cDNA
      library.

PMID- 8568917
TI  - Epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and
      basic fibroblast growth factor (bFGF) differentially influence neural precursor
      cells of mouse embryonic mesencephalon.
AB  - Growth factors are key elements in the process of neural cell differentiation. We
      examined the effects of classical mitogens on neural precursor cells, by
      culturing mouse cells of the embryonic (13.5 days postcoitum) mesencephalon and
      treating them with epidermal growth factor (EGF), transforming growth factor
      alpha (TGF-alpha), basic fibroblast growth factor (bFGF), nerve growth factor
      (NGF), and transforming growth factor-beta (TGF-beta). Our initial results show
      that EGF, TGF-alpha, or bFGF, but not NGF or TGF-beta, induced general
      proliferation of the cultured cells, followed by formation of colonies.
      Combinations of these three growth factors suggest that most cells with the
      capacity to form colonies responded to EGF, TGF-alpha, or bFGF. The number of
      colonies increased significantly when EGF, but not TGF-alpha, was used in
      combination with bFGF. Furthermore, a population responding only to EGF + bFGF
      was detected in the dorsal mesencephalon. The colony-forming activity of bFGF was
      dependent on insulin, but bFGF and insulin cooperation was indirect since we
      could not observe colony formation in subcultures of cells derived from colonies,
      even in the presence of insulin. Cells obtained from our colonies displayed
      neuronal and glial morphology and expressed markers of both neurons and
      astrocytes; nestin, a marker of neural precursor cells, was also expressed in the
      majority of colonies. Growth factors also influenced neuronal maturation; the
      best neurite outgrowth was obtained from cells derived from bFGF-induced colonies
      cultured in the presence of EGF + bFGF. These data indicate the existence of
      neural precursor cells in the embryonic mesencephalon that respond differentially
      to growth factors.

PMID- 8568918
TI  - Differentiation of serum-free mouse embryo cells into astrocytes is accompanied
      by induction of glutamine synthetase activity.
AB  - Serum-free mouse embryo (SFME) cells derived in a defined serum-free medium have
      been cultured for more than 200 generations and display properties of neural
      progenitor cells. SFME cells express the neuroepithelial stem cell marker nestin
      in defined serum-free medium. Exposure of SFME cells to transforming growth
      factor beta (TGF-beta) or serum decreases nestin expression and induces the
      astrocyte marker glial fibrillary acidic protein, suggesting that SFME cells
      differentiate into astrocytes upon exposure to TGF-beta or serum. We examined the
      expression by SFME cells of the functional central nervous system (CNS) astrocyte
      marker glutamine synthetase (GS). GS activity is induced in SFME cells upon
      exposure to TFG-beta or serum. The induction of GS activity was dose- and time
      dependent and was reversible. Retinoic acid, hydrocortisone, and dibutyryl cyclic
      AMP also induced GS expression. The induction of GS activity was accompanied by
      an increase in the level of GS mRNA and protein. This work provides further
      evidence that SFME cells represent neural progenitor cells which differentiate
      into functional astrocytes upon exposure to TGF-beta or serum.

PMID- 8568919
TI  - Growth related changes in sugar determinants on the surface of C6 glioma cells in
      culture: a cytochemical lectin-binding study.
AB  - The cell surface sugar determinants (CSSD) were examined in C6 glioma cells in
      cultures at different conditions of growth by peroxidase conjugates of the
      lectins: peanut agglutinin (PNA), Ricinus communis agglutinin (RCA), Helix
      pomatia agglutinin (HPA), wheat germ agglutinin (WGA), lentil agglutinin (LCA),
      laburnum bork agglutinin (LABA), and lotus agglutinin (TPA). It was found that
      the cells bound more intensively WGA, LCA, and RCA compared to PNA, HPA; the
      weakest staining was provided by LABA and TPA. Binding intensity for PNA
      significantly increased after pretreatment of the cells with neuraminidase. This
      indicates that a part of the beta-D-galactose residues on the surface membrane of
      C6 glioma cells is covered by sialic acid. The process of sialization was
      increased during the culturing of C6 glioma cells. Addition of cis-DDP or dBcAMP
      to cultures growing in medium with 10% of CS increased the number of Gal residues
      which are not covered by sialic acid. The expression of beta-D-galactose (Gal), N
      acetyl-D-galactosamine (NAcDGal), and fucose (Fuc) residues appeared to be most
      responsive to changes in growth conditions and degree of cell differentiation.
      The expressions of N-acetyl-D-glucosamine (NAcDGlc) and mannose (Man) residues
      were high and seems did not depend on changing of the conditions of culturing. In
      C6 glioma cells cultures in which the rate of cell division, formation of the
      cell processes, and adhesiveness of the cells to the substratum were reduced by
      growing cells in MEM+, expression of beta-Gal, NAcDGal, and Fuc was considerably
      reduced. The decrease of expression of beta-Gal, NAcDGal, and Fuc on the surface
      of cell membrane was more pronounced in MEM+ with 1% of CS than in MEM+ with 10%
      of CS. In DbcAMP and cis-DDP treated cultures, grown in medium with 1% serum, in
      which cell division was inhibited without obvious changes in cell adhesiveness to
      the substratum, binding of PNA and HPA was increased due to higher expression of
      beta-Gal and NAcDGal. From these observations it was concluded that the pattern
      of expression of sugar residues on the cell surface varies according to the
      biological state of the cells and are easily affected by tissue culture
      conditions.

PMID- 8568920
TI  - Ligands for EPH-related tyrosine kinase receptors are developmentally regulated
      in the CNS.
AB  - Elk is a member of the eph family of receptor-like tyrosine kinases. Although its
      function is unknown, elk is postulated to play a role in nervous system
      development. Using Northern analysis, we examined the developmental regulation of
      RNAs encoding elk, and several ligands for the eph family of RTKs, the LERKs.
      Expression of elk, LERK-1, and LERK-2 RNAs is high in all regions examined in the
      embryonic and postnatal rat brain and decreases to low levels with age. One
      exception is the adult olfactory bulb which continues to express a moderate level
      of LERK-2. In contrast, moderate LERK-4 expression was limited to the developing
      hippocampus and cerebral cortex. These data indicate that elk and some of the
      LERKs may play a role in nervous system development, maintenance, and/or
      regeneration.

PMID- 8568921
TI  - Hierarchical analysis of the nerve growth factor-dependent and nerve growth
      factor-independent differentiation signaling pathways in PC12 cells with protein
      kinase inhibitors.
AB  - The effects of a series of protein kinase inhibitors on nerve growth factor (NGF)
      dependent and NGF-independent neurite outgrowth in PC12 cells have established an
      ordered relationship among those protein kinases sensitive to down regulation by
      bryostatin, stimulation by staurosporine, inhibition by sphingosine, or
      inhibition by 6-thioguanine (6-TG). Quantitation of the biphasic staurosporine
      effects on NGF-induced neurite outgrowth (Hashimoto and Hagino: J Neurochem
      53:1675-1685, 1989) gave an IC50 of 2-4 nM for inhibition and an EC50 of 15-20 nM
      for induction of neurite extension. Both sphingosine and 6-TG inhibited neurite
      outgrowth induced by staurosporine and basic fibroblast derived growth factor
      (bFGF), as well as by NGF; therefore, sphingosine- and 6-TG-sensitive protein
      kinase steps occur after the convergence of the NGF, bFGF, and staurosporine
      signal pathways. Down regulation of protein kinase C by bryostatin chronic
      treatment, which inhibits NGF- and bFGF-induced neuritogenesis (Singh et al.:
      Biochemistry 33:542-551, 1994), did not inhibit the staurosporine-induced neurite
      outgrowth. Thus, the bryostatin-sensitive protein kinase C must occur subsequent
      to the convergence of the bFGF and NGF pathways, but before (or parallel to)
      staurosporine initiation of neurite outgrowth. In contrast, low concentrations of
      phorbol myristoyl acetate (PMA) or bryostatin, which activate protein kinase C
      activity, enhanced the staurosporine- or NGF-induced neurite extension. These
      data indicate that stimulation of one or more protein kinase C isozymes can
      synergistically interact with the signaling pathway to increase the rate of
      neuritogenesis. Inhibition by 5-7.5 nM staurosporine acted rapidly to arrest and
      decrease development of neurites up to 24 hr after NGF treatment, as did K252a
      and NGF polyclonal antibody addition. Our cellular data support the concept that
      staurosporine acts to inhibit the NGF receptor Trk (Nye et al.: Mol Biol Cell
      3:677-686, 1992), but that downstream steps can be activated by the higher
      concentration of staurosporine to bypass Trk and lead to neurite generation.
      Effects of staurosporine, 6-TG, and sphingosine on c-fos gene induction with or
      without NGF were not correlated with the generation of neurites. The sequence of
      protein kinases sensitive to these effectors appears to be in the order (but not
      consecutive) bryostatin, staurosporine, sphingosine, and 6-TG.

PMID- 8568922
TI  - Developmental regulation of Thy 1.2 rate of synthesis in the mouse cerebellum.
AB  - Thy 1.2 is a well-known major cell surface glycoprotein of the central nervous
      system (CNS). However, the regulation of the expression of this molecule as well
      as its function are yet to be determined. To approach these problems we studied
      the synthesis of the molecule in the developing cerebellum of wild-type and
      staggerer mutant mice. We found the appearance of a [35S]-methionine-labeled band
      detected with specific Sepharose 4B-bound monoclonal antibodies (Mabs). The Thy
      1.2 activity increases progressively from postnatal day 9 (P9), reaching the
      highest rate at P12, subsequently decreasing sharply at P13, and remaining
      relatively low up to P16 in the wild type. Comparison of these data to the rates
      of total protein synthesis reveals a selective developmental regulation of Thy
      1.2 expression, at least at the translational level. This correlates quite well
      with the timing of synaptic stabilization between parallel fibers and Purkinje
      cell dendritic spines. Furthermore, at P12 Thy 1.2 protein is preferentially
      located in the synaptosomal fraction. The parallel fiber:Purkinje cell synapsis
      is not stabilized in the staggerer mutant mouse. At P12 Thy 1.2 synthesis is 30%
      of the wild type, indicating that the translational regulation of Thy 1.2 is
      altered in the staggerer mutation.

PMID- 8568923
TI  - Activation of the hypothalamo-anterior pituitary corticotropin-releasing hormone,
      adrenocorticotropin hormone and beta-endorphin systems during the estradiol 17
      beta-induced plasma LH surge in the ovariectomized monkey.
AB  - The present work describes time-dependent changes in the content of corticotropin
      releasing hormone (CRH), adrenocorticotropin (ACTH), and beta-endorphin (beta-EP)
      in the hypothalamus (HT) and anterior pituitary (AP) and in the concentration of
      ACTH and beta-EP in the plasma during the 17 beta estradiol (E2) benzoate (E2B)
      induced luteinizing hormone (LH) surge in ovariectomized cynomolgus monkeys.
      Monkeys were euthanized at 0, 30, 48, 72, and 96 hr post-E2B. HT and AP were
      rapidly dissected, extracted in 2 N acetic acid containing 1 mM phenylmethane
      sulfonyl fluoride at 4 degrees C, and centrifuged at 18,000g for 30 min. Peptide
      concentrations were measured in the supernatant by specific radioimmunoassays
      (RIAs). In the HT, there were significant (P < 0.05) decreases in ACTH and beta
      EP content by 30 hr post-E2B and a significant (P < 0.05) decrease in HT CRH
      content 48 hr post-E2B. Thereafter, CRH, ACTH, and beta-EP content increased up
      to 72 hr post-E2B. In the AP, there was an almost linear decrease in the CRH
      content through 48 hr post-E2B followed by a marked 20-fold (P < 0.01) increase
      in the AP CRH content at 72 hr post-E2B, which corresponds to the time of the
      descending arm of the LH surge. The patterns of ACTH and beta-EP content were
      very similar in the AP, while that of CRH differed markedly. In contrast, in the
      HT CRH, ACTH, and beta-EP profiles were very similar. Significant (P < 0.05)
      increases in circulating levels of ACTH, beta-EP, and cortisol were evident at 30
      hr (all 3 hormones), 48 hr (beta-EP and cortisol), and 72 hr (cortisol) post-E2B,
      which corresponds with the time of decreased hypothalamic content of CRH, ACTH,
      and beta-EP. These results suggest that there maybe a marked activation of the
      hypothalamo-anterior pituitary-adrenal axis during the negative and positive
      feedback phases of the E2B-induced LH surge in the ovariectomized monkey.

PMID- 8568924
TI  - Norepinephrine but not epinephrine stimulates the release of corticotropin
      releasing factor from in vitro superfused rat hypothalamus.
AB  - To clarify the controversy concerning the role of catecholaminergic systems in
      regulating hypothalamic corticotropin-releasing factor (CRF) secretion, we
      assessed the direct effects of norepinephrine and epinephrine, alone and in
      association with mixed alpha and beta antagonists on hypothalamic CRF secretion.
      An in vitro rat mediobasal hypothalamus perifusion system was used, in which CRF
      secretion from a single explant was evaluated by a specific radioimmunoassay. We
      found that norepinephrine stimulated CRF secretion, with peak effects at 10(-8) M
      concentration, whereas epinephrine had no effect on CRF secretion. The effect of
      norepinephrine was antagonised by the mixed alpha antagonist phentolamine and by
      the mixed beta antagonist propranolol. We conclude that norepinephrine, but not
      epinephrine, stimulate hypothamic CRF secretion via alpha and beta receptors. The
      data support the idea that the central noradrenergic systems are excitatory upon
      CRF-41 secretion when acting directly at the hypothalamic level.

PMID- 8568925
TI  - Transmitter release by non-receptor activation of the alpha-subunit of guanine
      nucleotide regulatory protein in rat striatal slices.
AB  - The effects of 5 mM NaF + 10 microM AlCl3, a direct activator of guanine
      nucleotide-binding proteins (G proteins), on the release of [3H]dopamine
      ([3H]DA), [3H]gamma-aminobutyric acid ([3H]GABA), and [3H]acethylcholine
      ([3H]ACh) were investigated in slices of rat striatum. When the tissue was
      exposed to NaF + AlCl3 the release of [3H]DA, [3H]GABA, and [3H]ACh was enhanced
      significantly. In a calcium-free solution the release of [3H]GABA and [3H]DA was
      increased by NaF+AlCl3 much more than in the presence of [Ca2+]o. In slice
      preparations taken from reserpinized animals, in which the vesicular storage of
      [3H]DA was therefore prevented, NaF + AlCl3 had no effect on [3H]DA release. HPLC
      analysis of the radioactivity of the perfusate showed that, in the presence of
      NaF + AlCl3, the content of dihydroxyphenylacetic acid (DOPAC) in perfusate
      samples increased significantly, while in pargyline-treated animals only the DA
      content was increased. Inhibition of DA carriers by nomifensine or low
      temperature prevented the effect of NaF + AlCl3. N-ethylmaleimide (NEM)
      preincubation did not modify the effect of NaF + AlCl3 on [3H]DA release Neomycin
      (0.1 mM), a phospholipase C (PLC) inhibitor, significantly decreased the effect
      of NaF + AlCl3 on [3H]DA and [3H]GABA release. The internal concentration of Ca2+
      in synaptosomes was enhanced by NaF + AlCl3 in normal solution. However, [Ca2+]i
      was not influenced by NaF + AlCl3 in Ca(2+)-free medium. It is concluded that a
      non-receptor-mediated activation, by NaF + AlCl3, of the alpha-subunit of a G
      protein, results in a [Ca2+]o-independent release of DA and GABA, but not that of
      ACh.

PMID- 8568926
TI  - Calbindin D28K-containing neurons, and not HSP70-expressing neurons, are more
      resistant to HIV-1 envelope (gp120) toxicity in cortical cell cultures.
AB  - HIV-1-associated cognitive/motor complex is one of the major neurological
      complications of AIDS and is associated with neuronal loss. Gp120, the HIV
      envelope protein, is toxic for neurons in cultures and produces a rise in
      intracytosolic calcium. This neurotoxicity is dose-dependent and time-dependent.
      We evaluated the selective gp120 toxicity in primary neuronal cultures for
      calbindin-free and calbindin-containing neurons with semi-quantitative
      immunocytochemistry using an anti-calbindin D28K monoclonal antibody. The number
      of immunolabelled neurons was inversely correlated to neuronal survival. In
      cultures exposed to gp120 (100 pM) for 24 hr the neuronal survival of initial
      platings was 19.7 +/- 2.1% and the percentage of neuronal survival was 84.6 +/-
      4.9% in control cultures exposed to the vehicle. The corresponding percentages of
      immunolabelled neurons were 85.0 +/- 2.1% in treated cultures and 23.6 +/- 3.1%
      in control cultures (P < 0.001). The expression of heat shock proteins by heating
      cell cultures did not protect neurons from gp120 toxicity. These results suggest
      that calbindin D2K28-containing neurons are more resistant to gp120-toxicity in
      this cell culture system.

PMID- 8568927
TI  - Calpain secreted by activated human lymphoid cells degrades myelin.
AB  - Calpain secreted by lymphoid (MOLT-3, M.R.) or monocytic (U-937, THP-1) cell
      lines activated with PMA and A23187 degraded myelin antigens. The degradative
      effect of enzymes released in the extracellular medium was tested on purified
      myelin basic protein and rat central nervous system myelin in vitro. The extent
      of protein degradation was determined by SDS-PAGE and densitometric analysis.
      Various proteinase inhibitors were used to determine to what extent protein
      degradation was mediated by calpain and/or other enzymes. Lysosomal and serine
      proteinase inhibitors inhibited 20-40% of the myelin-degradative activity found
      in the incubation media of cell lines, whereas the calcium chelator (EGTA), the
      calpain-specific inhibitor (calpastatin), and a monoclonal antibody to m calpain
      blocked myelin degradation by 60-80%. Since breakdown products of MBP generated
      by calpain may include fragments with antigenic epitopes, this enzyme may play an
      important role in the initiation of immune-mediated demyelination.

PMID- 8568928
TI  - Advantages of using microfabricated extracellular electrodes for in vitro
      neuronal recording.
AB  - We describe fabrication methods and the characterisation and use of extracellular
      microelectrode arrays for the detection of action potentials from neurons in
      culture. The 100 microns2 platinised gold microelectrodes in the 64 electrode
      array detect the external current which flows during an action potential with S:N
      ratios of up to 500:1, giving a maximum recorded signal of several millivolts.
      The performance of these electrodes is enhanced if good sealing of the cells over
      the electrodes is obtained and further enhanced if the electrodes and the cells
      lie in a deep groove in the substratum. The electrodes can be used for both
      recording and stimulation of activity in cultured neurons and for recording from
      multiple sites on a single cell. The use of such electrodes to obtain recordings
      from invertebrate neurons is described. The particular advantages of these
      electrodes, their long term stability, non-invasive nature, high packing density,
      and utility in stimulation, are demonstrated.

PMID- 8568929
TI  - Myelin basic protein mRNA localization and polypeptide targeting.
AB  - Myelin basic proteins (MBPs), the major peripheral membrane proteins of central
      nervous system (CNS) myelin, are encoded by mRNAs that are selectively segregated
      to the myelinating processes of oligodendrocytes. In order to test whether the
      intracellular mechanisms responsible for MBP mRNA translocation are
      oligodendrocyte-specific, or alternatively, are present in other cell types and
      may therefore be more general, we have studied the localization of the 14 kD MBP
      mRNA and its encoded polypeptide (MBP14) in transiently transfected HeLa cells (a
      cervical carcinoma cell line) and in the rat pheochromocytoma cell line PC12.
      Unlike the situation in oligodendrocytes in situ, where MBP mRNAs are
      translocated and become "centrifugally" distributed, in both of the non-glial
      cells MBP mRNA was primarily detected in the perinuclear region. The MBP14
      polypeptide was found associated with intracellular membranes, and not
      exclusively with the plasma membrane. Our results indicate that the inability of
      HeLa and PC12 cells to correctly target MBP mRNAs to the cell periphery leads to
      a failure to incorporate MBP polypeptides directly into the plasma membrane.
      Further, the data lend credence to the concept that MBP mRNA segregation appears
      to be a specific feature of myelin-forming cells which is required for the
      precise delivery of the encoded polypeptides to the forming myelin membrane.

PMID- 8568931
TI  - Spontaneous opening of the acetylcholine receptor channel in developing muscle
      cells from normal and dystrophic mice.
AB  - Single-channel activity was recorded from cell-attached patches on skeletal
      muscle cells isolated from wild-type mice and from mice carrying the dy or mdx
      mutations. Spontaneous openings of the nicotinic acetylcholine receptor channel
      (nAChR) were detected in virtually all recordings from either dy/dy or dy/+
      myotubes, but only infrequently from wild-type or mdx myotubes. Spontaneous
      openings were also present in most recordings from undifferentiated myoblasts
      from all of the mouse strains studied. The biophysical properties of the
      spontaneous activity were similar to those of the embryonic form of the nAChR in
      the presence of acetylcholine (ACh). Examination of the single-channel currents
      evoked by low concentrations of ACh showed a reduced sensitivity to the agonist
      in the dystrophic dy and mdx myotubes, but not in wild-type myotubes. The results
      suggest that alterations in nAChR function are associated with the pathogenesis
      of muscular dystrophy in the dy mouse.

PMID- 8568930
TI  - Ion channels in rat microglia and their different sensitivity to
      lipopolysaccharide and interferon-gamma.
AB  - In order to study the voltage-dependent ion channels in microglia, and their
      possible modulation by pro-inflammatory substances like lipopolysaccharide (LPS)
      and interferon-gamma (IFN-gamma) we employed the patch-clamp technique on
      purified rat microglial cell subcultures grown for 1 - 5 days in control
      condition or after a 24 hour treatment with those agents. Regardless of the
      culture condition, almost 100% of the cells presented inward-rectifying (IR) K+
      currents identified by the following features: (a) extracellular K(+)-dependence
      of Vrev and whole-cell conductance; (b) inward-rectifying property; (c) channel
      blocking mechanism by Cs+; and (d) single channel conductance of 27 pS. A 'n'
      type outward-rectifying (OR) K+ current was present in 30% of the cells during
      the first 2 days of subcultivation. Its occurrence was strongly dependent on the
      preparation, varying from 0% to almost 80%, and it decreased to 13% of the cells
      after three days in culture. It showed the following features: (i) threshold of
      activation close to -30 mV; (ii) sigmoid current onset; (iii) voltage-dependent
      kinetics; and (iv) sensitivity to 4-aminopyridine (4-AP) and tetraethylammonium
      (TEA). Furthermore, we detected two ion currents not previously described in
      microglia: (i) a slowly activating outward current which appeared at potentials
      more positive than +20 mV and with a reversal potential close to 0 mV,
      tentatively identified as a proton current; and (ii) a Cl- conductance identified
      in ion substitution experiments as the current sensitive to the Cl- channel
      blocker SITS. The two agents, LPS (20 - 2,000 ng/ml) and IFN-gamma (10 - 100
      u/ml), shared the following effects: (a) enhancement of membrane capacitance, and
      (b) increase of OR current amplitude and frequency of occurrence. Moreover, IFN
      gamma was also able to increase IR current density, especially in cells with
      ameboid morphology, while LPS was ineffective. We conclude that the voltage
      dependent ion channel pattern of microglia is more complex than previously
      thought and that activating agents such as LPS and IFN-gamma share some
      electrophysiological effects, but differ in others.

PMID- 8568932
TI  - Immunolocalization of GLUT1 and GLUT3 glucose transporters in primary cultured
      neurons and glia.
AB  - Immunofluorescence analysis was used to study the cellular localization of
      glucose transporters 1 and 3 (GLUT1 and GLUT3) in primary rat neuronal and glial
      cultures. In primary cultured cerebellar granule neurons and cortical neurons,
      GLUT3 was detected in a pattern consistent with a generalized cell surface
      distribution. GLUT3 distribution corresponded most closely with the neural cell
      adhesion molecule (NCAM), and showed overlapping but distinct distributions
      compared to synaptophysin, microtubule-associated protein 2 (MAP2), neurofilament
      protein, and growth-associated protein (GAP43). Culture of neurons in the
      presence of glia did not alter the cellular localization of GLUT3. GLUT1 was
      detectable in primary cerebellar granule neurons both at the cell surface and in
      the cytoplasm, and appeared decreased in neurons cocultured with glia. GLUT1, but
      not GLUT3, was detected in glial fibrillary acidic protein (GFAP)-positive
      astrocytes present in mixed neuronal-glial cultures derived from cerebellum and
      cerebral cortex, as well as in cortical astrocyte cultures. GLUT1, but not GLUT3,
      was also detected in microglia and oligodendrocytes present in these cultures.
      This study indicates a generalized cell surface expression of the glucose
      transporters expressed in neurons and glia, rather than selective targeting to
      different cellular domains or subcellular locations.

PMID- 8568933
TI  - Response of olfactory Schwann cells to intranasal zinc sulfate irrigation.
AB  - The response of olfactory Schwann cells was assessed at 2, 4, and 7 days
      following intranasal zinc sulfate irrigation in 1-month-old mice. Ultrastructural
      and immunohistochemical observations showed dramatic differences between
      experimental and control mice which had been washed with saline intranasally. Two
      days after zinc sulfate treatment, many olfactory nerve bundles contained patchy
      areas of axonal degeneration, while the cell bodies of the olfactory Schwann
      cells appeared to have increased in electron density and to have shifted
      peripherally. Some of the cell bodies protruded from the surface of the axon
      fascicle, suggesting that the olfactory Schwann cells were in the initial process
      of migrating away. On the fourth day when most of the olfactory axons had
      degenerated, some olfactory Schwann cells were aligned immediately beneath the
      basal lamina of the olfactory epithelium. These cells were immunopositive for the
      S-100 protein and possessed an expanded perinuclear space. Many olfactory Schwann
      cells were present in the region beneath the cribriform plate, while some
      appeared to have passed through the gaps between the bony plates to reach the
      olfactory bulb. Hence, the results showed that many olfactory Schwann cells
      migrated towards the olfactory bulb following loss of axonal contact.
      Furthermore, on the seventh day following zinc sulfate treatment, some olfactory
      Schwann cells in the vicinity of the olfactory bulb appeared phagocytic, as
      indicated by their extension of processes around fragments of cell debris and the
      presence of lysosome-like organelles in the perikaryon. The control mice which
      had been intranasally irrigated with saline did not demonstrate massive olfactory
      axonal degeneration, and the morphology of the nasal cavity region was similar to
      that of normal mice.

PMID- 8568934
TI  - Perinatal morphine. I: Effects on synapsin and neurotransmitter systems in the
      brain.
AB  - We have previously shown that rat perinatal exposure to morphine causes
      dopaminergic and met-enkephalin (ME) and substance P (SP) changes in the striatum
      during the early postnatal period (Tenconi et al.: Int J Dev Neurosci 10: 517 -
      526, 1992); in addition it increases the susceptibility to neurotoxic lesions and
      impairs regenerative capacity of the serotoninergic system (Gorio et al.: J
      Neurosci Res 34: 462 - 471, 1993). Our study shows that ME and SP levels increase
      postnatally in several areas of the rat brain, reaching the highest values
      between 30 and 60 days, after which the peptide content subsides to lower levels.
      Perinatal exposure to morphine increases such ME and SP levels during the early
      stages of postnatal life. No effect of morphine on 5-HT and NE is observed, while
      the dopaminergic system is mainly affected in the mesencephalon. The pre- and
      postnatal brain expression of synapsin I mRNA is gradually and progressively
      localized in discrete areas of the brain. In the brain of rats perinatally
      exposed to morphine, the abundance of synapsin I mRNA expression is markedly
      reduced. Therefore, perinatal exposure to morphine affects early postnatal
      synaptic development in the brain as shown by the altered peptidergic and
      monoaminergic content and by the reduced synapsin I mRNA expression.

PMID- 8568935
TI  - Developmental changes of epidermal growth factor-like immunoreactivity in the
      human fetal brain.
AB  - We investigated the immunohistochemical localization of epidermal growth factor
      (EGF) in the developing human brain from 6 weeks of gestation to 3 months
      postpartum. EGF-like immunoreactivity varied in its localization and intensity
      according to the stage of development. At 10 - 20 weeks of gestation, EGF-like
      immunoreactivity appeared in proliferating and migrating cells in the cerebrum,
      disappeared thereafter, and appeared again in cortical neurons after 27 weeks of
      gestation. Astrocytes also showed EGF-like immunoreactivity from 27 weeks of
      gestation. These results suggest developmental regulation of EGF expression in
      the human brain, suggesting its physiological role in both neuronal and glial
      cells.

PMID- 8568936
TI  - Chronic opioid treatment of neuroblastoma x dorsal root ganglion neuron hybrid
      F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate
      levels and onset of naloxone-evoked decreases in membrane K+ currents.
AB  - Prolongation of the action potential duration of dorsal root ganglion (DRG)
      neurons by low (nM) concentrations of opioids occurs through activation of
      excitatory opioid receptors that are positively coupled via Gs regulatory protein
      to adenylate cyclase. Previous results suggested GM1 ganglioside to have an
      essential role in regulating this excitatory response, but not the inhibitory
      (APD-shortening) response to higher (microM) opioid concentrations. Furthermore,
      it was proposed that synthesis of GM1 is upregulated by prolonged activation of
      excitatory opioid receptor functions. To explore this possibility we have
      utilized cultures of hybrid F11 cells to carry out closely correlated
      electrophysiological and biochemical analyses of the effects of chronic opioid
      treatment on a homogeneous population of clonal cells which express many
      functions characteristic of DRG neurons. We show that chronic opioid exposure of
      F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic
      adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory
      supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent
      membrane K+ currents. Such elevation of GM1 would be expected to enhance the
      efficacy of excitatory opioid receptor activation of the Gs/adenylate
      cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that
      may account for the remarkable supersensitivity of chronic opioid-treated neurons
      to the excitatory effects of opioid agonists as well as antagonists. These in
      vitro findings may provide novel insights into the mechanisms underlying naloxone
      precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic
      opiate addiction in vivo.

PMID- 8568937
TI  - Characterization of a novel oligodendrocyte cell surface molecule.
AB  - Cell-type-specific reagents have proven useful in the analysis of central nervous
      system (CNS) development and function. Most markers of oligodendrocytes are
      components of myelin sheath, which in the CNS is the specific product of
      oligodendrocytes. We have isolated a novel monoclonal antibody termed 2B10 which
      was raised against embryonic rat spinal cord tissue. In adult rat cerebrum,
      cerebellum, and spinal cord, 2B10 immunoreactivity is predominantly localized in
      white matter. 2B10 immunoreactivity is absent from peripheral nerve, suggesting
      that in the nervous system the 2B10 antigen is restricted to the CNS. Dissociated
      cell culture studies indicate that 2B10 labels a cell surface molecule, and its
      cellular distribution is coincident with O1 and myelin basic protein-positive
      oligodendrocytes. By contrast, 2B10 does not label GFAP-positive astrocytes.
      These data suggest that in the CNS the 2B10 antigen is expressed specifically on
      oligodendrocytes. Biochemical analysis indicates that 2B10 recognizes a protein
      with an apparent molecular weight of approximately 79,000 in reducing sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. Developmentally, 2B10
      immunoreactivity is detectable in rat spinal cord at as early as embryonic day
      14. The relative abundance of this molecule decreases during myelination, but is
      maintained at a sustained level throughout adulthood. The 2B10 antigen appears
      not to be a myelin-associated protein since it is not detected in purified myelin
      fractions. 2B10 immunoreactivity is not detectable in extracts of rat sciatic
      nerve, heart, kidney, muscle, and skin, but is detectable in extracts of spleen
      and thymus. These data suggest that the 2B10 antigen is a novel cell surface
      molecule that is expressed on oligodendrocyte lineage cells throughout
      development.

PMID- 8568938
TI  - Developing oligodendroglia express mRNA for insulin-like growth factor-I, a
      regulator of oligodendrocyte development.
AB  - Insulin-like growth factors IGF-I and IGF-II are potent inducers of
      oligodendrocyte development. Because IGF-I is produced, in some cases, by the
      same cells that respond to it (autocrine/paracrine action), we examined the
      possibility that IGF-I is expressed by developing oligodendroglial cells. We
      employed a sensitive method, reverse transcriptase-polymerase chain reaction (RT
      PCR), to detect IGF-I mRNA in purified populations of oligodendroglial cells
      isolated from rat brain during the period of oligodendrocyte development. Cells
      were purified by fluorescence activated cell sorting (FACS), using antibodies to
      the cell surface antigenic markers O4 and galactocerebroside (GC). RNA was
      isolated from the sorted cells, reverse-transcribed, and PCR-amplified, using a
      strategy that recognizes IGF-I mRNA but not DNA. The amplified band was
      identified as IGF-I by size, hybridization to an IGF-I-specific antisense probe,
      and restriction analysis. IGF-I mRNA was detected in O4-positive/GC-negative
      oligodendrocyte precursors and, more weakly, in GC-positive oligodendrocytes. IGF
      I mRNA could be detected reproducibly in RNA extracted from 100-cell samples of
      O4-positive cells, making it unlikely that the mRNA was derived from contaminants
      in the FACS-sorted cell populations. We conclude that IGF-I is expressed by
      developing oligodendroglia. Autocrine expression of IGF-I by developing
      oligodendroglial cells suggests that oligodendrocyte development is, in part,
      autoregulatory.

PMID- 8568939
TI  - Dystroglycan expression in the wild type and mdx mouse neural retina: synaptic
      colocalization with dystrophin, dystrophin-related protein but not laminin.
AB  - Alpha- and beta-dystroglycan (alpha- and beta-DG) are members of a dystrophin
      associated glycoprotein complex (DGC) in skeletal muscle which binds to agrin and
      laminin, and has been postulated to be involved in myoneural snyapse formation.
      The absence of functional dystrophin in Duchenne muscular dystrophy (DMD) and in
      one of its animal models, the mdx mouse, leads to a reduction of alpha- and beta
      DG in muscle, and is often associated with mental retardation and abnormal
      retinal synaptic transmission in DMD. Using immunohistochemistry, we find that
      alpha- and beta-DG are expressed in the outer plexiform layer of both wild type
      and mdx retina, where both dystrophin and dystrophin-related protein (DRP), but
      not laminin are present. In situ hybridization identifies two neuronal
      populations, photoreceptors and retinal ganglion cells, that express DG mRNA.
      Alpha- and beta-DG are also expressed in the inner limiting membrane and around
      blood vessels where they colocalize with laminin and DRP. Western blot analysis
      revealed the expression of several dystrophin isoforms in wild type and mdx
      retina, possibly explaining the unaltered expression of alpha- and beta
      dystroglycan in the mdx central nervous system (CNS). Our results support the
      hypothesis that alpha- and beta-DG can interact with dystrophin and DRP in the
      CNS and perform functions analogous to those of the DGC in muscle.

PMID- 8568940
TI  - Selective block of Ca(2+)-dependent K+ current in crayfish neuromuscular system
      and chromaffin cells by sea anemone Bunodosoma cangicum venom.
AB  - The effects of the nematocyst venom of the sea anemone Bunodosoma cangicum on
      depolarization-activated currents were studies in opener crayfish muscle fibers
      and in cultured bovine chromaffin cells. The venom selectively and reversibly
      blocked the Ca(2+)-dependent K+ current (IK(Ca)) present in crayfish muscle in a
      dose-dependent manner without affecting voltage-gated Ca2+ or K+ currents.
      Furthermore, the venom also reduced IK(Ca) in chromaffin cells, without modifying
      voltage-gated Na+, Ca2+, or K+ currents. Synaptic transmission in crayfish muscle
      was also affected by the venom. Repetitive excitatory and inhibitory postsynaptic
      currents (each associated with a presynaptic action potential) were evoked by
      each nerve stimulus, suggesting that presynaptic IK(Ca) may control the
      electrical activity of excitatory and inhibitory presynaptic fibers. We conclude
      that B. cangicum venom includes a toxin that selectively and reversibly blocks
      Ca(2+)-dependent K+ currents in crayfish muscle and in bovine chromaffin cells,
      and modifies excitatory and inhibitory synaptic transmission, probably abolishing
      a similar conductance at the presynaptic fibers.

PMID- 8568941
TI  - Zebrafish neurons express two L1-related molecules during early axonogenesis.
AB  - Partial clones coding for two L1-related genes, zebrafish L1.1 and L1.2, were
      isolated from a zebrafish embryonic cDNA library. The homology analysis, based on
      the deduced amino acid sequences of L1.1 and L1.2, revealed that the two
      molecules are most closely related to each other and to mouse L1. Analysis by in
      situ hybridization revealed that during embryonic development of the nervous
      system the L1.1 and L1.2 messages are restricted to postmitotic neurons and that
      the onset of expression correlates with the initiation of axonogenesis. L1.1 is
      expressed by all known classes of neurons, consistent with an important general
      function during axonal outgrowth. Most of the neurons also express L1.2. However,
      L1.2 either is undetectable or is expressed at very low levels in the neurons of
      the olfactory placodes, anterior lateral line/acoustic ganglia complex, posterior
      lateral line ganglion, and in late developing hindbrain neurons. In the spinal
      cord, L1.2 message is detected only in a subpopulation of Rohon-Beard cells. This
      suggests the possibility that different levels of L1.2 expression may serve to
      distinguish different populations of neurons and their axons.

PMID- 8568942
TI  - Regulation of protease nexin-1 and angiotensin II receptor subtype 1 expression:
      inverse relationship in experimental models of nerve injury.
AB  - The up-regulation of PN-1 following nerve lesion has been investigated in vitro
      in cultures of dorsal root ganglion (DRG) explants, sciatic nerve segments, and
      isolated Schwann cells. In the first culture model, Schwann cells associated with
      neuronal processes synthesized small amounts of PN-1. Injury of the neurites
      emerging from the DRGs led to enhanced levels of PN-1 in Schwann cells located
      distal to the lesion site where degeneration of neuronal processes took place. In
      cultured sciatic nerve segments, PN-1 synthesis increased with a time-course
      comparable to that in ganglion explants following lesion. In the third model, PN
      1 levels gradually rose in isolated Schwann cells during the first 3-8 days in
      culture. Dissociation of Schwann cells from the sciatic nerve therefore causes an
      effect similar to nerve damage. Impairment of Schwann cells-neuron interactions
      was followed by a reduction in the expression levels of the angiotensin II (Ang
      II) receptor subtype AT1 in all three systems studied. Since the neuropeptide Ang
      II is able to repress PN-1 synthesis in cultured Schwann cells, loss of neuronal
      contact might decrease their responsiveness to Ang II, thus resulting in PN-1 up
      regulation by default.

PMID- 8568943
TI  - Regional and temporal profiles of c-fos and nerve growth factor mRNA expression
      in rat brain after lateral cortical impact injury.
AB  - Lesion-induced increases in NGF mRNA are thought to be mediated by c-fos gene
      expression. Conversely, NGF induction of c-fos expression has been reported
      following administration of exogenous NGF. However, the relationship between c
      fos and NGF gene expression after traumatic injury to the intact brain is not
      known. Thus, we applied in situ hybridization and semiquantitative reverse
      transcription-polymerase chain reaction (RT-PCR) methods to determine temporal
      profiles of c-fos and NGF mRNA expression in rat brains after controlled impact
      to the exposed cortex. Using alternate sections from the same rat brains, in situ
      hybridization studies showed that in neocortex, c-fos mRNA transiently increased
      at 30 min, 1 hr, and 3 hr after injury, while there were no increases of NGF mRNA
      at these postinjury time points. In the hippocampus, in situ hybridization showed
      that c-fos mRNA increased at 30 min, 1 hr and 3 hr postinjury, while NGF mRNA
      increased at 1 hr, 3 hr but not at 30 min after injury. RT-PCR studies in
      hippocampus confirmed that c-fos mRNA increased as early as 5 min after injury,
      peaked at 30 min postinjury, and remained elevated 5 hr postinjury. Levels of
      hippocampal NGF mRNA expression increased by 1 hr after injury and plateaued
      until 3 and 5 hr postinjury. These data are consistent with the possible
      regulatory role of endogenous c-fos on NGF expression following traumatic brain
      injury.

PMID- 8568944
TI  - Blockade of K+ channels induced by AMPA/kainate receptor activation in mouse
      oligodendrocyte precursor cells is mediated by Na+ entry.
AB  - AMPA/kainate receptor activation in cultured oligodendrocyte precursor cells from
      embryonic mouse cortex leads to a blockade of delayed rectifying K+ currents. In
      the present study, we provide evidence using the patch-clamp technique in the
      whole-cell configuration that the mechanism linking kainate receptor activation
      and K+ conductance blockade is due to the receptor-mediated Na+ entry: 1) The
      blockade was not observed in Na(+)-free bathing solution nor when intracellular
      [Na+] was elevated by dialzying the cell with a pipette solution containing high
      [Na+]. 2) Elevation of intracellular [Na+] alone led to a blockade of outward
      currents in contrast to cells dialyzed by sucrose. High [Li+]i also reduced the
      outward currents, and in Li(+)-containing bathing solution the kainate-induced
      blockade of K+ channels was more pronounced. Probably, Li+ accumulates
      intracellularly after permeation through the receptor pore due to slower
      extrusion mechanisms. Experiments with GTP gamma S or GDP beta S and pertussis
      toxin indicated that GTP-binding protein-mediated mechanisms were not of
      importance for the kainate-induced K+ conductance blockade. Our data suggest that
      in glial precursor cells AMPA/kainate receptor activation leads to an
      intracellular [Na+] increase which blocks delayed rectifying K+ channels.

PMID- 8568946
TI  - Maternal and child health in Saudi Arabia. Study design and methodology.
AB  - Saudi Maternal and Child Health Survey was designed to study the utilisation of
      maternal health services by ever-married women of child-bearing age, by measuring
      level of tetanus vaccination coverage; breastfeeding and weaning knowledge,
      attitude and practices; and by measuring the level of vaccination coverage with
      BCG, DPT, Poliomyelitis and measles vaccines among children 1-2 years old at the
      national level. The standard world health organization (WHO) cluster technique
      was employed. The kingdom was divided into five geographical areas. The sampling
      frame used was available at the Ministry of Health (MOH) in the form of ascending
      cumulative frequency tables where the catchment areas of 1625 health centres (HC)
      constitute primary sampling units (PSUs). Thirty clusters were randomly selected
      from each of the five geographic areas, and 40 household per cluster were used.
      The target populations included: (i) the ever-married Saudi females in the child
      bearing age (15-49 years), (ii) children less than 5 years old, and (iii)
      children 1-2 years old. The respondents were interviewed using a questionnaire.
      The quality of data was assured by pre-coding of data which was edited throughout
      the field work period. A 4-day workshop was held for the interviewers and
      supervisors 48 hours prior to commencement of the survey. During the workshop,
      interviewers were instructed to read the questions precisely, were acquainted
      with survey methodology in general, pretested the questionnaire, received guide
      manual, instruction notes, progress sheets and follow-up formats for referring to
      when needed. The investigators were in the field during the first few days to
      solve any problem arising.

PMID- 8568945
TI  - Laminin overrides the inhibitory effects of peripheral nervous system and central
      nervous system myelin-derived inhibitors of neurite growth.
AB  - Axon growth inhibitory proteins associated with central nervous system (CNS)
      myelin are responsible in part for the absence of long distance axon regeneration
      in the adult mammalian CNS. We have recently reported that myelin-associated
      glycoprotein (MAG), which is also present in peripheral nerves, is a potent
      inhibitor of neurite growth. This was surprising given the robust regenerative
      capacity of peripheral nerves. We now provide evidence that myelin purified from
      peripheral nerve also has neurite growth inhibitory activity. However, this
      activity can be masked by laminin, which is a constituent of the Schwann cell
      basal lamina. We also report that laminin, which is largely absent from the
      normal adult mammalian CNS, when added to purified CNS myelin, can override the
      neurite growth inhibitory activity in CNS myelin. These results have important
      implications for the development of strategies to foster axon regeneration in the
      adult mammalian CNS where multiple growth inhibitors exist.

PMID- 8568947
TI  - Antenatal care, attitudes, and practices.
AB  - This paper discusses attitudes and practices of antenatal care in Saudi Arabia,
      based on the results of the maternal and child health survey of 1991. The survey
      covered a cluster random sample of 6306 households, with 6294 ever-married Saudi
      women 15-49 years of age out of whom 1050 were pregnant. The interview
      questionnaire included maternal care data on current pregnancies and births in
      the sample, totaling 4777 children less than 5 years old. Coverage of antenatal
      care and frequency of visits among pregnancies identified, by whom and where, and
      reasons for not attending antenatal services by age, urban-rural, geographical,
      and educational differentials. Proportions pregnant at the time of the survey
      were 17 per cent; antenatal care attendance for the whole sample reached 86 per
      cent; frequencies of one or two visits were 37 per cent; and three or four visits
      25 per cent; those checked by a physician were 85 per cent, while 88 per cent
      attended governmental facilities. Those with timely attendance were 85 per cent.
      However, almost one-third of non-attenders (30 per cent) believed they did not
      need antenatal care. Though utilization of antenatal care services is already
      high, it has to be further increased through health education and publicity,
      emphasizing the couples role.

PMID- 8568948
TI  - Coverage and quality of natal and postnatal care: women's perceptions, Saudi
      Arabia.
AB  - This paper discusses natal and postnatal care services in Saudi Arabia, as
      revealed by the National Maternal & Child Health Survey of 1991. The latter was
      based on a national random sample of 150 clusters, with 6306 households, from
      urban and rural areas, of five geographic regions. The target of 6294 ever
      married Saudi women, 15-49 years old included 6020 currently married women, of
      whom 1050 reported a pregnancy. Data on maternal care were analysed, including
      where and why natal care was attended, and for both natal and postnatal care, how
      much and by whom, by respondents' age, urban-rural residence, geographical
      location, and education of wife and husband. About three-quarters of the
      respondents had one or more births within the 5 years preceding the survey, with
      a total of 4777 children under six. Institutional deliveries reached 86 per cent
      and about 90 per cent of deliveries were attended by physicians or nurses with a
      ratio of 2:1. Postnatal care attendance amounted to 88 per cent mainly by
      physicians than nurses with a ratio of 5:1. In general, the above results
      describe relatively high coverage with natal and postnatal care services, which
      can still be improved through health education and community support,
      particularly of the women. Judging by the high level of institutional care and
      physician involvement, good quality of care is implied, but needs to be further
      confirmed, by defining morbidity and mortality patterns.

PMID- 8568949
TI  - Overview on breastfeeding patterns in Saudi Arabia.
AB  - A national cross-sectional study was carried out in 1991 to investigate child
      feeding patterns in addition to other MCH issues. The target population was the
      last live birth born within 5 years preceding the data of the interview. The data
      were collected by interviewing the mothers of the eligible children using a
      precoded questionnaire. The total sample size was 3608 children and their mothers
      were chosen randomly through a multistage cluster sampling technique with
      representation of different regions. The results observed revealed a previous
      history of breastfeeding among 92.4 and 94.5 per cent of urban and rural studied
      children, respectively. The mean duration of breastfeeding among studied children
      in the urban and rural communities, were 11 and 13 months, respectively.
      Illiteracy of the parents was associated with a longer breastfeeding duration.
      Moreover, the results revealed that, the higher the current age of mothers, the
      longer the average duration of breastfeeding. Governmental health facilities and
      mass media constituted the main source of essential information about child
      feeding. The results are further interpreted and suitable recommendations are
      made.

PMID- 8568950
TI  - Role of social factors in the prevalence of diarrhoeal diseases in under-five
      Saudi children.
AB  - Social factors influencing diarrhoea prevalence rates, in Saudi communities, were
      studied during 1991 taking statistically representative samples from the whole
      population. The factors included mother's age, child's age, birth order, parent's
      education, feeding pattern, and urban, rural, and regional residences. This study
      was a part of the National Maternal and Child Health Survey which involved
      interviewing of 6308 women with 8292 children under 5 years. The social factors
      and diarrhoea occurring in children during the preceding 14 days prior to the
      date of survey were inquired into and recorded in the pre-coded and field-tested
      questionnaire forms. There were 3.8 episodes of diarrhoea per year per child
      under 5 or 15 per cent per 2 weeks. This was higher than previously reported. The
      factors associated with higher prevalence rate were the children of youngest (15
      19-years-old) mothers (28 per cent), the last children (18 per cent), and the
      children aged 6-17 months (24-31 per cent). Additionally, by birth order, the
      last (third) child on the average had highest rate (18 per cent) than the second
      (9 per cent) and the second had higher rate than the first (6 per cent) child.
      The rate in those who lived in rural setting was higher (15 per cent) than in
      those who lived in urban setting (14 per cent). The rates were almost identical
      between the areas of the country (13-17 per cent) except having higher rate in
      the northern area (17 per cent).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8568951
TI  - ORS use in diarrhoea in Saudi children: is it adequate?
AB  - The prevalence of diarrhoea and especially the pattern of diarrhoea therapy in
      Saudi children under 5 years were studied as a part of the Maternal and Child
      Health Survey during 1991. A statistically representative sample of over 6300
      mothers, from all over the country was interviewed by trained nurses. There were
      3.8 episodes of diarrhoea per child under 5 per year. For treating diarrhoea,
      ORS, salt-sugar solution (SSS), other available solutions, intravenous fluid and
      various drugs were the therapeutic agents. In 73 per cent of cases ORS, nearly 3
      per cent SSS, 33 per cent other solutions and in over 4 per cent intravenous
      fluid were used. Anti-diarrhoeal drugs and antibiotics were used in over 40 per
      cent of cases. Over 9 per cent of cases did not use any treatment. Young mothers
      used ORS at a higher rate (84 per cent) for their children compared to the
      average for all (73 per cent). Children of illiterate parents used ORS at a
      higher rate than children of literate parents. In urban area, the use-rate was
      lower (68 per cent) than in rural area (80 per cent). The regional use-rates were
      almost similar excepting a higher rate in the northern area. In over 87 per cent
      of cases, advice on diarrhoea therapy was obtained from government health centres
      (physicians/nurses), while only 3 per cent of the diarrhoea cases acquired
      information from national media. The overall use-rate of ORS was thus better than
      many other countries and there was a 25 per cent increase over the previous Saudi
      findings in 1987.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8568952
TI  - National Immunization Coverage Survey Saudi Arabia, 1991.
AB  - A nationwide survey was carried-out aiming at determination of immunization
      coverage level against the six killer diseases of childhood (tuberculosis,
      diphtheria, pertussis, tetanus, poliomyelitis, and measles). Variations between
      geographical zones, urban-rural settings, age, education and mother's employment,
      father's education, and child's birth order were studied. The standard WHO
      cluster technique was used. The sample (1102 children) was restricted to Saudi
      children 1-2 years old. Interviewers were exposed to training and methods of
      calibration, and involved in a pilot survey. Nationally, the survey showed very
      high coverage levels, BCG was the highest (99 per cent), measles was the lowest
      (90 per cent), whereas the three doses of DPT (diphtheria, pertussis and tetanus)
      and TOPV (trivalent oral polio vaccine) were in between (98, 96 and 94 per cent,
      respectively). There was no marked differences between urban-rural settings. The
      western zone showed the lowest coverage by all vaccines. The national coverage by
      the six vaccines reached 86 per cent correctly immunized (according to WHO
      standards), 14 per cent partially immunized and 1 per cent non-immunized.
      Immunization coverage was higher for children to younger mothers. The non
      immunized group belonged exclusively to illiterate mothers (1 per cent). Children
      to mothers with basic education showed the highest coverage (88 per cent). Birth
      order had negative effect on coverage. Nationally, 88 per cent of children had
      immunization certificate while 12 per cent had not. The eastern and central zones
      had the highest percentages of children with certificates (92 and 91 per cent,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8568953
TI  - Nuptiality pattern in Saudi Arabia.
AB  - The data of this work are based on the 'Saudi Maternal and Child Health Survey'
      conducted in 1991. This was a nationwide house to house field survey. The study
      included 6294 ever-married Saudi female in the childbearing age who represent the
      target population. They were randomly selected from both urban and rural settings
      of the five geographical areas of Saudi Arabia. The mean current age of the
      sample of ever-married women was 31 years and the mean age at first marriage was
      17 and 16 years for urban and rural females, respectively. Education was
      associated with upward shift of the age at first marriage. About 20 per cent of
      the sampled ever-married Saudi females got married before their 15th birthday and
      83 per cent before reaching 20 years of age. These percentages are even higher in
      rural than urban settings. The overall percentage of women who were currently
      married at the time of the survey was 96 per cent. The divorced and widowed women
      of childbearing age were 2 and 3 per cent, respectively, of the total. Husband's
      educational level had positive impact on the frequency of divorce. The latter was
      highest among women married to illiterate husbands with a dose response pattern.
      Comparison has been made with the situation 4 years ago. An increase in literacy
      rates among Saudi ever-married women and their husbands was observed, however, a
      significant (P < 0.05) difference still exists between female and male literacy
      rates (38 and 71 per cent, respectively). The events of early marriage, before
      the age of 15 years, became less frequent. There is an overall decline in teenage
      marriages which explains a large part of the recent changes observed in
      nuptiality and pattern of birth in Saudi Arabia.

PMID- 8568954
TI  - Fetal arterial Doppler studies in twin-twin transfusion syndrome.
AB  - This cross-sectional study investigates the circulatory profile of the donor and
      recipient fetuses in pregnancies with twin-twin transfusion syndrome manifested
      by acute polyhydramnios during the second trimester of pregnancy. Doppler
      investigations of the umbilical arteries and of the fetal descending thoracic
      aortas and middle cerebral arteries were performed in both fetuses of 27
      pregnancies with twin-twin transfusion syndrome at 18 to 25 (mean, 21.7) weeks'
      gestation. Significant differences from normal values were increased umbilical
      artery pulsatility index and decreased aortic mean velocity in both donor and
      recipient fetuses, decreased middle cerebral artery pulsatility index in
      recipients and decreased middle cerebral artery mean velocity in donors.
      Increased umbilical artery pulsatility index in some donor and recipient fetuses
      may be the consequence of abnormal placental development and polyhydramnios
      related compression, respectively. Doppler findings in the fetal circulation are
      compatible with hypovolemia in the donor and hypervolemia with congestive heart
      failure in the recipient.

PMID- 8568955
TI  - Effect of pressure on echocardiographic videodensity from sonicated albumin: an
      in vitro model.
AB  - The effect of different pressures (0, 10, 30, 60, 80, 100, 120, or 180 mm Hg) on
      the ultrasound contrast effect obtained from sonicated albumin was evaluated by
      videodensity decay curves in an in vitro model immersed in a water tank. Decay
      rates and half-times were calculated from the videodensity decay curves at each
      pressure. A significant (P < 0.0001) relation was found between contrast
      disappearance and pressure: the higher the pressure the more rapid the contrast
      disappearance. Release of pressure did not result in contrast reappearance.
      Contrast decrease with pressure may result from microbubble destruction or
      alteration in acoustic properties by pressure. These findings may help explain
      the limited success of sonicated albumin for systemic ultrasonographic
      arteriography and myocardial perfusion imaging after intravenous injection. An
      ideal contrast agent for contrast echo studies should be stable at physiologic
      pressures.

PMID- 8568956
TI  - The empty amnion: a sign of early pregnancy failure.
AB  - Between 6.5 to 10 weeks of gestation, the length of the amniotic cavity is
      similar to that of the embryo. It follows that by the time an amniotic sac is
      detectable sonographically, an embryo of equal length should also be visualized.
      Retrospective review of case records at our institution revealed 15 patients in
      whom the amnion was visualized in the absence of an embryonic pole during first
      trimester sonography (endovaginal and transvesical). Indications for sonographic
      examination included gestational age estimation, discrepant size and dates, or
      vaginal bleeding. The mean sac diameter for the 15 gestations ranged from 14 to
      36 mm, corresponding to gestational ages of 6.1 to 9.5 weeks. Ages based on the
      last menstrual period ranged from 6.1 to 11 weeks. A yolk sac was identified in
      all cases in addition to the amniotic sac, but neither an embryo nor cardiac
      pulsations were observed. In 12 of the 15 cases the size of the gestational sac
      was greater than 16 mm, such that the absence of an embryo also met an accepted
      criterion for a failed pregnancy. Follow-up in all cases confirmed early
      pregnancy failure. In this series the demonstration of an "empty amnion"
      (visualization of an amnion but no identifiable embryonic pole) was always
      associated with pregnancy loss. The "empty amnion" sign is helpful as an
      additional finding confirming early pregnancy failure.

PMID- 8568957
TI  - Role of color Doppler imaging in differentiating between pseudocystic malignant
      tumors and fluid collections.
AB  - The differentiation between a pseudocystic solid tumor and a fluid collection
      containing echoes is sometimes difficult. The purpose of this study was to
      evaluate the contribution of color Doppler sonography in confirming the solid
      nature of pseudocystic malignant tumors by demonstrating internal vascularity.
      Fourteen consecutive masses with an indeterminate solid or cystic appearance on
      conventional sonograms were evaluated with color Doppler sonography for the
      presence of blood flow within the boundaries of the mass. Color Doppler
      sonography demonstrated the presence of some blood flow in all 12 solid malignant
      tumors, whereas no flow was visualized in the two fluid collections. By
      demonstrating the presence of internal blood flow in solid tumors, color Doppler
      sonography can rapidly confirm the solid nature of markedly hypoechoic malignant
      tumors that mimic fluid collections on conventional sonograms.

PMID- 8568958
TI  - Color Doppler sonographic findings in patients with transitional cell carcinoma
      of the bladder and renal pelvis.
AB  - The purposes of this study were (1) to evaluate the color Doppler sonographic
      findings in patients with transitional cell carcinoma of the bladder and renal
      pelvis, (2) to determine if color Doppler sonography could predict tumor grade
      and stage, and (3) to determine whether tumor vascularity is related to size. A
      total of 15 patients with 16 bladder transitional cell carcinomas and one patient
      with renal pelvic transitional cell carcinoma were evaluated prospectively with
      transabdominal color Doppler ultrasonography. The presence or absence of visible
      vascularity and the resistive index were correlated with tumor size, cytologic
      grade, and tumor stage. Statistical analysis was performed with Fisher's exact
      test. Seven (41%) of 17 tumors had visible vascularity: five (45%) of 11 high
      grade transitional cell carcinomas were vascular, whereas two (33%) of six low
      grade transitional cell carcinomas were vascular (P = 1.00). Three of five (60%)
      of the invasive lesions were vascular, but the vascularity was not predictive of
      tumor stage (P = 0.593). The vascular high-grade tumors tended to have more
      numerous and larger visible vessels than the vascular low-grade lesions. No tumor
      smaller then 23 mm was vascular, but the size of the tumor was not predictive of
      the vascularity (P = 0.1172). The resistive index was measurable in six tumors,
      but it was not predictive of grade or stage. Color Doppler ultrasonography is not
      helpful clinically in the evaluation of transitional cell carcinoma as tumor
      grade, stage, and size are not related to vascularity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8568959
TI  - Transrectal and transperineal sonography during guided intrauterine procedures.
AB  - Transrectal sonography was used to provide intraoperative guidance for dilatation
      and curettage and placement of intrauterine tandem apparatus in 20 patients in
      whom the external cervical os could not be visualized adequately. Transrectal
      sonography was found to be useful in providing guidance for these procedures and
      at the same time helped avoid uterine perforation. This method also was used
      during cerclage placement in two patients who had undergone several conizations.
      Transperineal sonography was used in three patients whose area of abnormality was
      best approached transperineally. These cases included transvaginal biopsy of a
      metastatic trophoblastic tumor and one guided aspiration of a perirectal abscess
      after pelvic exenteration. The potential advantages and pitfalls in the
      intraoperative use of transrectal and transperineal sonography for guided
      intrauterine procedures are discussed and illustrated.

PMID- 8568960
TI  - Transvaginal color and pulsed Doppler sonography of the endometrium: a possible
      role in reducing the number of dilatation and curettage procedures.
AB  - The objectives of the study were to establish color and pulsed Doppler
      sonographic characteristics of uterine vascularity in postmenopausal patients
      with pathologic endometrium in order to reduce the number of unnecessary
      diagnostic dilatation and curettage procedures. The prospective study involved 42
      postmenopausal patients who were examined, prior to dilatation and curettage
      operation, with transvaginal color and pulsed Doppler sonography. Twenty patients
      had symptoms such as vaginal bleeding or clinically enlarged uterus and 22
      postmenopausal women, from our screening group, were asymptomatic. Endometrial
      thickness (cut-off value of 8 mm), rates of visualization, and the density of
      uterine, myometrial (peritumoral) and endometrial (intratumoral) vessels were
      used, along with pulsatility and resistive indices of these vessels, to assess
      and correlate with endometrium pathology. Endometrial thickness was greater than
      8 mm in all cases of endometrial carcinoma (14 of 14 cases), endometrial
      hyperplasia (eight of eight cases), and one endometrial polyp. In all cases of
      uterine myoma (nine cases) and in asymptomatic controls (11 subjects) the
      endometrium thickness was below 8 mm. Percentage of visualization of myometrial
      and endometrial vessels in cases of endometrial carcinoma was 93% and 43%
      respectively, which was significantly higher than for cases with benign
      endometrium (P < 0.05). RI and PI values of these studied vessels of endometrial
      carcinoma were significantly lower than those for endometrial hyperplasia (P <
      0.05). In 80% of cases of endometrial carcinoma, dense vascularity was found in
      the myometrium (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8568961
TI  - Sonographic diagnosis of arteriovenous fistula in pancreas transplant.

PMID- 8568962
TI  - Sonographic appearance of testicular sarcoid.

PMID- 8568963
TI  - Prospective diagnosis of moyamoya disease with Doppler ultrasonography.

PMID- 8568964
TI  - Occult fetal bowel obstruction: ileal atresia presenting in a newborn infant
      after normal antenatal sonography.

PMID- 8568965
TI  - Sonographic characteristics in low-grade endometrial stromal sarcoma: a report of
      two cases.

PMID- 8568966
TI  - Focal sparing of liver parenchyma in steatosis: role of the gallbladder and its
      vessels.
AB  - The purpose of this study was to determine the prevalence and localization of
      focal areas of sparing in a population of patients with fatty infiltration
      (steatosis) of the liver. We also sought to determine if the blood supply of the
      gallbladder has an effect on fatty infiltration of the liver adjacent to it. We
      studied 290 patients with sonographic signs of fatty infiltration of the liver
      with gray scale sonography. In 58 of the patients, the gallbladder had been
      removed previously. A zone of focal sparing was found in 67% of patients with
      liver steatosis (78% in patients with an intact gallbladder versus 33% in
      patients with previous cholecystectomy). In patients with an intact gallbladder,
      segments 4 and 5 were spared most often. These segments were rarely spared in
      patients with previous cholecystectomy. Other sites of focal sparing were
      observed with the same frequency in the two groups. We conclude that focal
      sparing occurs frequently in patients with liver steatosis, especially in
      segments 4 and 5. When the gallbladder is absent, areas of focal sparing are less
      frequent, and they rarely involve segments 4 and 5. This suggests that the blood
      supply of the gallbladder plays a role in the distribution of the fat in the
      adjacent liver. Focal sparing might serve as an additional sign in the diagnosis
      of steatosis of the liver, especially in patients with an intact gallbladder.

PMID- 8568967
TI  - Monitoring postprandial size of the proximal stomach by ultrasonography.
AB  - The purpose of this study was to develop a sonographic method to monitor
      postprandial size of the proximal stomach. Twenty-three healthy persons were
      scanned in a sitting position with a 3.25 MHz transducer after ingestion of 500
      ml meat soup. The area in a sagittal section and the maximal diameter in an
      oblique frontal section were chosen as standard measurements. The soup emptied
      from the proximal stomach in a linear manner (r = 0.99) and at a rate of 2.0 +/-
      1.3%/min. Intraobserver error of the scans (mean +/- SD) was 5.6% +/- 2.3% and
      9.5% +/- 4.5% for sagittal area and frontal diameter, respectively, and the
      corresponding interobserver error was 5.3% +/- 4.0% and 8.3% +/- 5.3%,
      respectively. This sonographic method demonstrated a moderate day-to-day
      variation, had low intra- and interobserver error, and allowed estimation of
      initial emptying fractions of the proximal stomach.

PMID- 8568968
TI  - Color Doppler imaging of the eye: normal ranges, reproducibility, and observer
      variation.
AB  - Color Doppler ultrasonography has numerous potential applications in the
      diagnosis and monitoring of many ocular disease processes. One of its advantages
      over other investigative and diagnostic tests is its safety and repeatability. To
      be able to fully assess this technique it is important to have good control data
      and to know the reproducibility of the technique for each of the retrobulbar
      vessels. Color Doppler ultrasonography was performed on 80 volunteers, and normal
      ranges of blood velocity were calculated for the ophthalmic artery and for the
      central retinal artery and vein. Reduction in the peak systolic and end diastolic
      velocities in the ophthalmic artery and an increase in resistive index in the
      central retinal artery and vein were noted with advancing age. With regard to
      reproducibility of the retrobulbar vessels, 15 healthy persons were chosen at
      random and intra- and interobserver studies performed. The most reliable and
      reproducible vessels were the ophthalmic artery and central retinal artery and
      vein. Greater variation was noted in the posterior ciliary vessels, whereas the
      superior ophthalmic and vortex veins were unreliable in both detection and
      velocity measurement. The results provide normal ranges for future studies and
      demonstrate that reproducible results can be obtained for the orbital vasculature
      using color Doppler imaging.

PMID- 8568969
TI  - Endovaginal ultrasonographic measurement of early embryonic size.

PMID- 8568970
TI  - Puppy love can be therapeutic, too.

PMID- 8568971
TI  - Sick kids find help in a Cyberspace world.

PMID- 8568972
TI  - From the Food and Drug Administration.

PMID- 8568974
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      1995-96 season.

PMID- 8568975
TI  - Zinc supplementation during pregnancy.

PMID- 8568973
TI  - From the Centers for Disease Control and Prevention. Update: alcohol-related
      traffic crashes and fatalities among youth--United States, 1982-1994.

PMID- 8568976
TI  - Zinc supplementation during pregnancy.

PMID- 8568977
TI  - Physician-assisted suicide.

PMID- 8568978
TI  - Physician assisted suicide.

PMID- 8568980
TI  - Physician assisted suicide.

PMID- 8568979
TI  - Physician assisted suicide.

PMID- 8568981
TI  - Screening for tuberculosis.

PMID- 8568982
TI  - Screening for tuberculosis.

PMID- 8568983
TI  - Migrating docs: studying physician practice location.

PMID- 8568984
TI  - Effects of weight loss vs aerobic exercise training on risk factors for coronary
      disease in healthy, obese, middle-aged and older men. A randomized controlled
      trial.
AB  - OBJECTIVE: To compare the effects of weight loss vs aerobic exercise training on
      coronary artery disease risk factors in healthy sedentary, obese, middle-aged and
      older men. DESIGN: Randomized controlled trial. SUBJECTS: A total of 170 obese
      (body mass index, 30 +/- 1 kg/m2 [mean +/- SEM]), middle-aged and older (61 +/- 1
      years) men. INTERVENTIONS: A 9-month diet-induced weight loss interventions, 9
      month aerobic exercise training program, and a weight-maintenance control group.
      MAIN OUTCOME MEASURES: Change in body composition, maximal aerobic capacity (V02
      max), blood pressure, lipoprotein concentrations, and glucose tolerance. RESULTS:
      Forty-four of 73 men randomized to weight loss completed the intervention and had
      a 10% mean reduction in weight (- 9.5 +/- 0.7 kg; P < .001), with no 22 change in
      VO2 max. Forty-nine of 71 men randomized to aerobic exercise completed the
      intervention, increased their VO2 max by a mean of 17% (P < .001), and did not
      change their weight, whereas the 18 men who completed in the control group had no
      significant changes in body composition or VO2 max. Weight loss decreased fasting
      glucose concentrations by 2%, insulin by 18%, and glucose and insulin areas
      during the oral glucose tolerance test (OGTT) by 8% and 26%, respectively (P <
      .01). By contrast, aerobic exercise did not improve fasting glucose or insulin
      concentrations or glucose responses during the OGTT but decreased insulin areas
      by 17% (P < .001). In analysis of variance, the decrement in fasting glucose and
      insulin levels and glucose areas with intervention differed between weight loss
      and aerobic exercise when compared with the control group (P < .05). Similarly,
      weight loss but not aerobic exercise increased high-density lipoprotein
      cholesterol levels (+ 13%) and decreased blood pressure compared with the control
      group. In multiple regression analyses, the improvement in lipoprotein and
      glucose metabolism was related primarily to the reduction in obesity.
      CONCLUSIONS: These results suggest that weight loss is the preferred treatment to
      improve coronary artery disease risk factors in overweight, middle-aged and older
      men.

PMID- 8568985
TI  - Effectiveness of bystander cardiopulmonary resuscitation and survival following
      out-of-hospital cardiac arrest.
AB  - OBJECTIVE: To examine the independent relationship between effectiveness of
      bystander cardiopulmonary resuscitation (CPR) and survival following out-of
      hospital cardiac arrest. DESIGN: Prospective observational cohort. SETTING: New
      York City. PARTICIPANTS: A total of 2071 consecutive out-of-hospital cardiac
      arrests meeting Utstein criteria. INTERVENTION: Trained prehospital personnel
      assessed the quality of bystander CPR on arrival at the scene. Satisfactory
      execution of CPR required performance of both adequate compressions and
      ventilations in conformity with current American Heart Association guidelines.
      MAIN OUTCOME MEASURE: Adjusted association between CPR effectiveness and
      survival. Survival was defined as discharge from hospital to home. RESULTS:
      Outcome was determined on all members of the inception cohort--none were lost to
      follow-up. When the association between bystander CPR and survival was adjusted
      for effectiveness of CPR in the parent data set (N = 2071), only effective CPR
      was retained in the logistic model (adjusted odds ratio [OR] = 5.7; 95%
      confidence interval [CI], 2.7 to 12.2; P < .001). Of the subset of 662
      individuals (32%) who received bystander CPR, 305 (46%) had it performed
      effectively. Of these, 4.6% (14/305) survived vs 1.4% (5/357) of those with
      ineffective CPR (OR = 3.4; 95% CI, 1.1 to 12.1; P < .02). After adjustment for
      witness status, initial rhythm, interval from collapse to CPR, and interval from
      collapse to advanced life support, effective CPR remained independently
      associated with improved survival (adjusted OR = 3.9; 95% CI, 1.1 to 14.0; P <
      .04). CONCLUSION: The association between bystander CPR and survival in out-of
      hospital cardiac arrest appears to be confounded by CPR quality. Effective CPR is
      independently associated with a quantitatively and statistically significant
      improvement in survival.

PMID- 8568986
TI  - Serum gonadotropins and steroid hormones and the development of ovarian cancer.
AB  - OBJECTIVE: To prospectively examine the association between endogenous hormones
      and development of ovarian cancer. DESIGN: Nested case-control study. SETTING: A
      population-based serum bank in Washington County, Maryland. PARTICIPANTS: Serum
      samples were collected in 1974 from 20305 county residents and stored at -70
      degrees C. From 1975 through 1989, a total of 31 cases of ovarian cancer were
      identified in women who were not taking hormones at the time of blood collection.
      These cases were matched to 62 controls on age, menopausal status, and, for
      premenopausal women, number of days from the beginning of the last menstrual
      period. MAIN OUTCOME MEASURE: Prediagnostic endogenous hormone levels of cases
      and controls were compared. RESULTS: Mean follicle-stimulating hormone levels
      were lower among cases (43.3 IU/L) compared with controls (54.4 IU/L) (P = .04),
      and increasing levels were associated with significantly lower risk (P for trend
      = .01), particularly among postmenopausal women. Luteinizing hormone levels were
      9% lower among cases than controls, but the difference was not statistically
      significant (P = .39). Compared with controls, cases had higher androstenedione
      levels (4.5 nmol/L vs 3.3 nmol; P = .03) and higher dehydroepiandrosterone (DHEA)
      levels (15.9 nmol/L vs 9.7 nmol/L; P = .02). The risk of ovarian cancer increased
      with higher levels of androstenedione and DHEA sulfate (P for trend = .008 and
      .11, respectively). These associations were not materially different between
      premenopausal and postmenopausal women. CONCLUSION: The results suggest that
      women with low serum gonadotropin levels or high androgen levels have an
      increased risk of ovarian cancer. These findings do not support the hypothesis
      that pituitary gonadotropins increase the risk of ovarian cancer. Replication of
      the study in other populations is highly desirable.

PMID- 8568987
TI  - Somatization and medicalization in the era of managed care.
AB  - Somatization, the reporting of somatic symptoms that have no pathophysiological
      explanation, appears to be increasing as sociocultural currents reduce the
      public's tolerance of mild symptoms and benign infirmities and lower the
      threshold for seeking medical attention for such complaints. These trends
      coincide with a progressive medicalization of physical distress in which
      uncomfortable bodily states and isolated symptoms are reclassified as diseases
      for which medical treatment is sought. Somatization and medicalization are likely
      to become more problematic in the era of managed care. Under capitation,
      providers will have greater incentives to reduce utilization, and somatizing
      patients may feel forced to express their "disease" in more urgent and
      exaggerated terms in order to gain access to the physician. In addition, prepaid
      subscribers will suffer little financial disincentive to seek medical attention
      for relatively minor complaints; therefore, they are likely to increase the
      demand for physician consultation. This situation suggests an urgent need to
      improve the management of somatizing patients. Innovative consultative,
      behavioral, and educational interventions are now available. In addition, medical
      professionals should greet the process of medicalization with considerable
      caution and educate the public more about the normative presence of symptoms and
      bodily distress in healthy people. Additional research is needed into
      somatization and its relationship to the demand for medical care. In an era of
      managed care, increased attention should be devoted to understanding and
      controlling the demand for care, a large portion of which is symptom driven.

PMID- 8568988
TI  - The Cochrane Collaboration. Preparing, maintaining, and disseminating systematic
      reviews of the effects of health care.

PMID- 8568989
TI  - Is noncentral obesity metabolically benign? Implications for prevention from a
      population survey.
AB  - OBJECTIVE: To determine if individuals who are overall obese but have low waist
      to-hip ratios have unfavorable lipid profiles, blood pressures, and glucose
      statuses. DESIGN: Cross-sectional study. SETTING: The Manitoba Heart Health
      Survey surveyed a representative sample of residents of the Canadian province of
      Manitoba. PARTICIPANTS: --A total of 2,792 adults aged 18 to 74 years were
      interviewed, 2,339 of whom underwent clinical examinations. MAIN OUTCOME
      MEASURES: Blood pressure, fasting plasma glucose, total cholesterol,
      triglycerides, high-density lipoprotein, and low-density lipoprotein measurements
      were compared across categories of body mass index (BMI) and waist-to-hip ratio
      (WHR). MAIN RESULTS: Manitobans with noncentral obesity tend to occupy positions
      between those of the nonobese and the centrally obese in terms of the effect on
      blood pressure, plasma lipids, and glucose. In multiple linear regression models
      involving age, BMI, and WHR as independent variables and one of the metabolic
      variables as dependent variables, both BMI and WHR are significant independent
      predictors of most metabolic variables. Where both are significant, BMI tends to
      be the stronger predictor, with a larger standardized regression coefficient.
      CONCLUSIONS: Noncentral obesity is not metabolically benign; BMI as an overall
      measure of obesity is as important as, and sometimes more important than, WHR in
      predicting metabolic effects. The recognition of the epidemiological significance
      of the WHR as a centrality measure of obesity should not divert attention from
      the metabolic risk status of noncentrally obese individuals who require continued
      health education to reduce weight.

PMID- 8568990
TI  - The relationship between methodological quality and conclusions in reviews of
      spinal manipulation.
AB  - OBJECTIVE: To study the relationship between the methodological quality and other
      characteristics of reviews of spinal manipulation for low back pain on the one
      hand and the reviewers' conclusions on the effectiveness of manipulation on the
      other hand. DATA SOURCES: Reviews identified by MEDLINE search, citation
      tracking, library search, and correspondence with experts. STUDY SELECTION:
      English- or Dutch-language reviews published up to 1993 dealing with spinal
      manipulation for low back pain that include at least two randomized clinical
      trials (RCTs). DATA EXTRACTION: Methodological quality was assessed using a
      standardized criteria list applied independently by two assessors (range, 0% to
      100%). Other extracted characteristics were the comprehensiveness of the search,
      selective citation of studies, language, inclusion of non-RCTs, type of
      publication, reviewers' professional backgrounds, and publication in a spinal
      manipulation journal or book. The reviewers' conclusions were classified as
      negative, neutral, or positive. DATA SYNTHESIS: A total of 51 reviews were
      assessed, 17 of which were neutral and 34 positive. The methodological quality
      was low, with a median score of 23%. Nine of the 10 methodologically best reviews
      were positive. Other factors associated with a positive reviewers' conclusion
      were review of spinal manipulation only, inclusion of a spinal manipulator in the
      review team, and a comprehensive literature search. CONCLUSIONS: The majority of
      the reviews concluded that spinal manipulation is an effective treatment for low
      back pain. Although, in particular, the reviews with a relatively high
      methodological quality had a positive conclusion, strong conclusions were
      precluded by the overall low quality of the reviews. More empirical research on
      the review methods applied to other therapies in other professional fields is
      needed to further explore our findings about the factors related to a positive
      reviewers' conclusion.

PMID- 8568991
TI  - A 50-year-old woman with disabling spinal stenosis.

PMID- 8568992
TI  - NIH consensus conference. Cochlear implants in adults and children.
AB  - OBJECTIVE: To provide clinicians and other health care providers with a current
      consensus on the benefits, limitations, and technical and safety issues that need
      to be considered in the use of cochlear implants. PARTICIPANTS: A nonfederal,
      nonadvocate, 14-member consensus panel representing the fields of otolaryngology,
      audiology, speech-language pathology, pediatrics, psychology, and education, and
      including a public representative. In addition, 24 experts in auditory anatomy
      and physiology, otolaryngology, audiology, aural rehabilitation, education,
      speech-language pathology, and bioengineering presented data to the consensus
      panel and a conference audience of 650. EVIDENCE: The literature was searched
      through MEDLINE and an extensive bibliography of references was provided to the
      panel and the conference audience. Experts prepared abstracts with relevant
      citations from the literature. Scientific evidence was given precedence over
      clinical anecdotal experience. CONSENSUS: The panel, answering predefined
      consensus questions, developed its conclusions based on the scientific evidence
      presented in open forum and the scientific literature. CONSENSUS STATEMENT: The
      panel composed a draft statement that was read in its entirety and circulated to
      the experts and the audience for comment. Thereafter, the panel resolved
      conflicting recommendations and released a revised statement at the end of the
      conference. The panel finalized the revisions within a few weeks after the
      conference. CONCLUSIONS: Cochlear implantation improves communication ability in
      most adults with severe-to-profound deafness and frequently leads to positive
      psychological and social benefits as well. Currently, children at least 2 years
      old and adults with profound deafness are candidates for implantation. Cochlear
      implant candidacy should be extended to adults with severe hearing impairment and
      open-set sentence discrimination that is less than or equal to 30% in the best
      aided condition. Access to optimal education and (re)habilitation services is
      important for adults and is critical for children to maximize the benefits
      available from cochlear implantation.

PMID- 8568993
TI  - Meta-analysis of randomized controlled trials. A concern for standards;.

PMID- 8568994
TI  - Weight control and exercise. Cardinal features of successful preventive
      gerontology.

PMID- 8568997
TI  - Nocebos contribute to host of ills.

PMID- 8568996
TI  - A piece of my mind. Do you have a minute?

PMID- 8568998
TI  - FDA gets feedback on informed consent waiver.

PMID- 8569000
TI  - Finding the most reliable dope on doping.

PMID- 8568999
TI  - Tougher drug tests for Centennial Olympic Games.

PMID- 8569001
TI  - From the Veterans Health Administration.

PMID- 8569002
TI  - From the Centers for Disease Control and Prevention. Outbreak of Salmonella
      serotype typhimurium infection associated with eating raw ground beef--Wisconsin,
      1994.

PMID- 8569003
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      United States, 1995-96 season.

PMID- 8569004
TI  - Prenatal and neonatal HIV testing.

PMID- 8569005
TI  - Alcohol interventions in trauma centers.

PMID- 8569006
TI  - Alcohol interventions in trauma centers.

PMID- 8569007
TI  - Alcohol interventions in trauma centers.

PMID- 8569008
TI  - Chronic fatigue syndrome and neurally mediated hypotension.

PMID- 8569009
TI  - Chronic fatigue syndrome and neurally mediated hypotension.

PMID- 8569010
TI  - Chronic fatigue syndrome and neurally mediated hypotension.

PMID- 8569011
TI  - Survival following bacteremia with resistant organisms.

PMID- 8569012
TI  - HIV and physical examination skills.

PMID- 8569013
TI  - Transfusion vs anesthesia-related hepatitis.

PMID- 8569014
TI  - Nosocomial infections in intensive care units.

PMID- 8569015
TI  - Bone lead levels and delinquent behavior.
AB  - OBJECTIVE: To evaluate the association between body lead burden and social
      adjustment. DESIGN: Retrospective cohort study. SETTING: Public school community.
      PARTICIPANTS: From a population of 850 boys in the first grade at public schools,
      503 were selected on the basis of a risk scale for antisocial behavior. All of
      the 850 boys who scored in the upper 30th percentile of the distribution on a
      self-reported antisocial behavior scale were matched with an equal number drawn
      by lot from the lower 70% of the distribution. From this sample, 301 students
      accepted the invitation to participate. EXPOSURE MEASURE: K x-ray fluorescence
      spectroscopy of tibia at subjects' age of 12 years. MAIN OUTCOME MEASURES: Child
      Behavior Checklist (CBCL), teachers' and parents' reports, and subjects' self
      report of antisocial behavior and delinquency at 7 and 11 years of age. RESULTS:
      Subjects, teachers, and parents were blind to the bone lead measurements. At 7
      years of age, borderline associations between teachers' aggression, delinquency,
      and externalizing scores and lead levels were observed after adjustment for
      covariates. At 11 years of age, parents reported a significant lead-related
      association with the following CBCL cluster scores: somatic complaints and
      delinquent, aggressive, internalizing, and externalizing behavior. Teachers
      reported significant associations of lead with somatic complaints,
      anxious/depressed behavior, social problems, attention problems, and delinquent,
      aggressive, internalizing, and externalizing behavior. High-lead subjects
      reported higher scores in subjects' self-reports of delinquency at 11 years. High
      lead subjects were more likely to obtain worse scores on all items of the CBCL
      during the 4-year period of observation. High bone lead levels were associated
      with an increased risk of exceeding the clinical score (T > 70) for attention,
      aggression, and delinquency. CONCLUSION: Lead exposure is associated with
      increased risk for antisocial and delinquent behavior, and the effect follows a
      developmental course.

PMID- 8569016
TI  - Effects of hormone replacement therapy on endometrial histology in postmenopausal
      women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The
      Writing Group for the PEPI Trial.
AB  - OBJECTIVE: To report the histological findings of the endometrium of
      postmenopausal women who were randomized to receive placebo, estrogen only, or
      one of three estrogen plus progestin (E+P) regimens in the Postmenopausal
      Estrogen/Progestin Interventions (PEPI) Trial. DESIGN: A 3-year multicenter,
      randomized, double-masked, placebo-controlled trial. PARTICIPANTS: A total of 596
      postmenopausal women aged 45 through 64 years without contraindication to hormone
      therapy. INTERVENTION: Participants were randomized and stratified in equal
      numbers to one of the following treatments in 28-day cycles: placebo, 0.625 mg/d
      of conjugated equine estrogens (CEE), 0.625 mg/d of CEE plus 10 mg/d of
      medroxyprogesterone acetate (MPA) for the first 12 days, 0.625 mg/d of CEE plus
      2.5 mg/d of MPA, or 0.625 mg/d of CEE plus 200 mg/d of micronized progesterone
      (MP) for the first 12 days. OUTCOME MEASURE: Histology of endometrium collected
      at baseline, annual, or unscheduled visits by biopsy, curettage, or hysterectomy.
      ANALYSIS: Intention to treat. RESULTS: During follow-up women assigned to
      estrogen alone were more likely to develop simple (cystic), complex
      (adenomatous), or atypical hyperplasia than those given placebo (27.7% vs 0.8%,
      22.7% vs 0.8%, and 11.8% vs 0%, respectively) for the same types of hyperplasia
      (P < .001). Participants administered one of the three E+P regimens had similar
      rates of hyperplasia as those given placebo (P = .16). The occurrence of
      hyperplasia was distributed evenly across the 3 years of the trial. Women taking
      estrogens alone also had more unscheduled biopsies (66.4% vs 8.4%; P < .001) and
      curettages (17.6% vs 0.8%; P < .001) than women receiving placebo. The number of
      surgical procedures was similar for women receiving placebo and women receiving
      the E+P regimens (P = .38). Of the 45 women with complex (adenomatous) or
      atypical hyperplasia, study medications were discontinued in all, and the biopsy
      results of 34 (94%) of 36 women with hyperplasia reverted to normal with
      progestin therapy. The remainder had dilatation and curettage (n = 2) or
      hysterectomy with (n = 2) or without (n = 6) prior medical therapy, or refused
      further biopsies (n = 1). One woman developed adenocarcinoma of the endometrium
      while receiving placebo. CONCLUSIONS: At a dosage of 0.625 mg, the daily
      administration of CEE enhanced the development of endometrial hyperplasia.
      Combining CEE with cyclic or continuous MPA or cyclic MP protected the
      endometrium from hyperplastic changes associated with estrogen-only therapy.

PMID- 8569017
TI  - Parenteral ketorolac and risk of gastrointestinal and operative site bleeding. A
      postmarketing surveillance study.
AB  - OBJECTIVE: To evaluate the risk of gastrointestinal and operative site bleeding
      associated with the use of parenteral ketorolac tromethamine. DESIGN:
      Postmarketing surveillance inception cohort study. SETTING: A total of 35
      hospitals throughout the Philadelphia, Pa, region, 1991 to 1993. PATIENTS:
      Patients administered 10,272 courses of parenteral ketorolac therapy were
      compared with patients administered 10,247 courses of a parenteral opiate who
      were matched to the ketorolac patients by hospital, admitting service, and date
      of initiation of study drug. MAIN OUTCOME MEASURES: Medical records were reviewed
      for demographics, medical history, doses and duration of study drug, various
      aspects of the hospital course including surgery and concomitant medications, and
      adverse events. RESULTS: The multivariate adjusted odds ratio (OR) comparing
      ketorolac with opiates for gastrointestinal bleeding was 1.30 (95% confidence
      interval [CI], 1.11 to 1.52); for operative site bleeding, the OR was 1.02 (95%
      CI, 0.95 to 1.10). The OR was elevated further in subjects 75 years of age or
      older for both gastrointestinal bleeding (OR = 1.66; 95% CI, 1.23 to 2.25) and
      operative site bleeding (OR = 1.12; 95% CI, 0.94 to 1.35). A dose-response
      relationship was evident between average daily ketorolac dose and both
      gastrointestinal bleeding and operative site bleeding (trend test P < .001 for
      both). When analgesic therapy lasted 5 or fewer days, ketorolac was associated
      with only a small increased risk of gastrointestinal bleeding (OR = 1.17; 95% CI,
      0.99 to 1.30); when therapy was prolonged beyond 5 days, the OR was 2.20 (95% CI,
      1.36 to 3.57). The association of ketorolac with operative site bleeding was not
      affected by duration of therapy. CONCLUSIONS: The overall associations between
      ketorolac use and both gastrointestinal bleeding and operative site bleeding are
      small. However, the risk associated with the drug is larger and clinically
      important when ketorolac is used in higher doses, in older subjects, and for more
      than 5 days. Improving physicians' prescribing practices by limiting the dose and
      duration of ketorolac use, especially in the elderly, should enhance its overall
      risk-benefit balance.

PMID- 8569019
TI  - Evaluating new vaccines for developing countries. Efficacy or effectiveness?
AB  - Despite the profusion of promising new vaccines against illnesses prevalent in
      developing countries, uncertainties about the balance between costs and benefits
      of new vaccines have retarded their use in public health practice. Conventional
      prelicensure trials of vaccine protection exacerbate these uncertainties by
      focusing on measurement of vaccine efficacy--the performance of a vaccine under
      idealized conditions. Vaccine effectiveness trials provide a more pragmatic
      perspective by addressing the performance of a vaccine under the ordinary
      conditions of a public health program, by capturing direct as well as indirect
      effects of vaccination, and by comprehensively addressing outcomes of public
      health concern. The use of effectiveness trials should enable more rational
      triaging of new vaccines for developing countries and may accelerate the
      introduction of new vaccines into public health practice by resolving speculative
      debates about practical costs and benefits.

PMID- 8569018
TI  - Initial experience with partial liquid ventilation in adult patients with the
      acute respiratory distress syndrome.
AB  - OBJECTIVE: To evaluate the safety and efficacy of partial liquid ventilation
      (PLV). DESIGN: Before-after trial. SETTING: The surgical intensive care unit at
      the University of Michigan, Ann Arbor, from April to December 1994. PATIENTS: A
      consecutive sample of 10 patients aged 19 to 55 years with the acute respiratory
      distress syndrome who were receiving extracorporeal life support. INTERVENTION:
      Perflubron was administered into the trachea until the dependent zone of the lung
      was filled. Gas ventilation of the perflubron-filled lung was then performed
      (PLV). Volatilized perflubron replacement was repeated daily for from 1 to 7 days
      with a median cumulative dose of 38 mL/kg (range, 15 to 62 mL/kg). MAIN OUTCOME
      MEASURES: Physiologic shunt and static pulmonary compliance. RESULTS: Physiologic
      shunt decreased from a median of 0.72 (range, 0.37 to 1.0) to 0.46 (range, 0.21
      to 0.96) over the 72 hours following initiation of PLV (P = .01 by repeated
      measures analysis of variance). Static pulmonary compliance corrected for patient
      weight increased from a median of 0.16 mL/cm H2O per kilogram (range, 0.01 to
      0.48 mL/cm H2O per kilogram) to 0.27 mL/cm H2O per kilogram (range, 0.05 to 1.11
      mL/cm H2O per kilogram) over the same time period (P = .04 by repeated measures
      analysis of variance). Overall survival was five (50%) of 10 patients.
      Complications that were potentially associated with PLV included pneumothorax
      development in one patient and mucus plug formation in one patient. CONCLUSIONS:
      Perflubron may be safely administered into the lungs of patients with severe
      respiratory failure receiving extracorporeal life support and may be associated
      with improvement in gas exchange and pulmonary compliance.

PMID- 8569020
TI  - Utility of emergency, telephone-based national surveillance for Hantavirus
      pulmonary syndrome. Hantavirus Task Force.
AB  - On May 27, 1993, in response to the outbreak investigation of newly recognized
      Hantavirus pulmonary syndrome (HPS) in the Four Corners states (New Mexico,
      Arizona, Utah, and Colorado), the Centers for Disease Control and Prevention
      established a national surveillance case definition for severe, unexplained
      respiratory disease to determine the extent of HPS throughout the United States.
      A toll-free telephone hotline number was instituted to provide updated
      information about unexplained respiratory illness and to serve as a passive
      mechanism for reporting suspected cases. Clinical information was obtained from
      callers reporting suspected cases, and diagnostic specimens and medical record
      reviews were requested from health care providers. From June 3 through December
      31, 1993, the hotline received 21,443 telephone inquiries; callers identified 280
      suspected cases living outside the Four Corners states with at least one specimen
      available for diagnostic testing. By December 31, 1993, 21 confirmed cases (age
      range, 14 to 58 years) residing in 11 states outside the Four Corners region had
      been identified. This passive surveillance system was successful in rapidly
      identifying the widespread sporadic geographic distribution for HPS cases
      throughout the United States and could serve as a model for similar emergencies.
      Expanding and coordinating surveillance systems for the early detection,
      tracking, and evaluation of emerging infections is a critical component of
      disease prevention.

PMID- 8569021
TI  - New approaches to the control of infections caused by antibiotic-resistant
      bacteria. An industry perspective.

PMID- 8569022
TI  - Measuring children's antisocial behaviors.

PMID- 8569023
TI  - Innovative life support in the acute respiratory distress syndrome.

PMID- 8569025
TI  - Assisting medical students with undiagnosed ADHD.

PMID- 8569024
TI  - Medical student abuse during third-year clerkships.

PMID- 8569026
TI  - Autism: talking in a world without language.

PMID- 8569027
TI  - [Autoantibodies to coagulation factors].

PMID- 8569028
TI  - [Activated coagulation factors in various thrombotic diseases].
AB  - Various hemostatic abnormalities have been reported and excess activation of
      coagulation factors, such as prothrombin, factor VII, factor IX, and factor XI,
      have been detected in thrombotic diseases states by various assay systems. We
      recently developed the enzyme-linked differential immunoassay for activated
      factor XI-alpha 1 antitrypsin complex (FXIa-alpha 1 AT) and applied it with other
      assays for activated factors such as thrombin-antithrombin III complex (TAT) to
      detect the hypercoagulable state in clinical samples. In patients with DIC, the
      FXIa-alpha 1 AT level in plasma increased before onset of DIC. In patients with
      non-insulin-dependent diabetes mellitus, FXIa-alpha 1AT and TAT levels were
      increased in the patient plasma. FXIa-alpha 1AT was related to the severity of
      urinary albumin excretion, whereas TAT was not. Plasma FXIa-alpha 1AT levels were
      significantly increased in patients with angiographically proven coronary artery
      disease, and showed a positive correlation with TAT, fibrinogen, and Lp(a).
      Evaluation of activated coagulation factor provides useful information on the
      diagnosis of thrombotic disease.

PMID- 8569029
TI  - [Activated factor VII as a new cardiovascular risk factor of atherothrombotic
      disease].
AB  - Factor VII (FVII) is a plasma vitamin K-dependent glycoprotein that plays an
      important role in the initiation of tissue factor-induced coagulation (extrinsic
      pathway of blood coagulation). An increase in FVII coagulant activity (FVIIc) has
      been proposed as an independent risk factor for coronary artery disease.
      Recently, the coagulation assay using soluble tissue factor(sTF) enables us to
      measure the plasma levels of the activated form of factor VII(FVIIa) without the
      effect of the FVII zymogen form. We have developed the fluorogenic assay for
      FVIIa using sTF and measured the plasma FVIIa in atherosclerotic diseases. The
      FVIIa level in the Japanese was lower than that reported in Caucasians,
      suggesting that the incidence of ishemic heart disease is lower in the former.
      The FVIIa level was higher in the patients with cardiovascular diseases (ischemic
      heart disease and cerebral infarction), non-insulin-dependent diabetic mellitus,
      hypertension with microalbuminuria, and renal failure than in the healthy
      controls. The FVIIa levels were also increased in non-insulin-dependent diabetic
      patients, and this FVIIa increase was positively correlated with urinary albumin
      excretion. Furthermore, FVIIa levels were not correlated with the levels of
      lipids and the activity of hepatic synthesis, indicating that FVIIa may be an
      independent risk factor for cardiovascular disease.

PMID- 8569031
TI  - [Idea and practice with the systematization of clinical laboratory in the Central
      Laboratory, Osaka University Hospital].
AB  - On 1 September 1993, we left our old hospital and moved to our brand new
      establishment, and at that time we adopted the order-entry and reporting system.
      In this paper we report on our new laboratory computer system that has been
      developed to manage a lot of information and to analyze rapidly many test tubes
      (4000 samples per day) and to elevate the service for our patients. We developed
      the automated clinical laboratory system and this new system was named as the
      Clinical Laboratory Supervised System (CLASSY). We used the NEC system 3500 Model
      10, NEC N5200 Model 03 sx and NEC PC9821 Ae as a laboratory host computer, an
      interface unit and a terminal for routine work, respectively. CLASSY covers the
      automated analysis not only for clinical chemistry, but also for hematology,
      urinalysis and microbiology. As the ordering and reporting system is applied to
      the hospital information system, order information for clinical test is
      transferred to our laboratory host computer when the bar-code label is printed
      out from the automatic bar-code labeller. Then it is transferred from the
      laboratory host computer to some subsystems or automatically to an analyzer
      through the interface units or modems.

PMID- 8569030
TI  - [Some aspects of newly developed instruments for blood coagulation tests].
AB  - Five newly developed instruments for five routine blood coagulation tests
      including prothrombin time, APTT, thrombotest, normotest and fibrinogen assay and
      the other specialized tests were introduced by each manufacturer. In four
      instruments, the principal of clot detection is based on the change of optical
      density due to fibrin thread. One instrument detects viscosity change. All
      instruments were easy to use due to full-automation, and the precision and
      accuracy in one laboratory use were high in quality. There were difficult
      problems when a user switches from the reagent recommended by the manufacturer to
      another commercially available one. The user needs to re-evaluate the standard
      curve using international reference plasma. In Japan, international normalized
      ratio (INR) presentation of prothrombin time is not common even in a large scale
      laboratory. When a patient with warfarin moves to another hospital, the
      presentation of prothrombin time from the former laboratory can not be used
      because of the difference in reagent and equipment. Much confusion concerning
      prothrombin time occurred due to differences in reagent and equipment after the
      Hanshin-Awaji earthquake. Many patients taking warfarin had to evacuate under
      severe stress condition, and had prothrombin time out of the optimal therapeutic
      range not knowing whether it was due to quake-stress or intra-laboratory
      difference. Selection of automated coagulation instrument which can easily print
      out the INR in prothrombin time is recommended.

PMID- 8569032
TI  - [Management of total laboratory system and its efficacy].
AB  - The Osaka City University Hospital was reopened in May 1993. In the Central
      Clinical Laboratory our Total Laboratory Automation System, a comprehensive
      online analyzing system, covers the entire process from collecting blood to
      completing tests. Our study showed that an average of 2,800 outpatients were
      examined per day in 1994, compared with 1,900 per day in 1992, an increase of
      47.4%. The number of tests performed by the central laboratory in 1994 was
      5,610,000 as compared to 3,720,000 in 1992, an increase of 50.8%. After the
      installation of the transport line and computerization the following can be
      noted: 1) We were able to extend reception hours by two hours. 2) We are now able
      to assign lab medical technologists to physiology analysis, emergency analysis,
      and initial outpatient testing. We conclude that these effects have been very
      large.

PMID- 8569033
TI  - [Systematization in the Central Clinical Laboratory of Kyoto University
      Hospital].
AB  - Recently, computer systems including several delivery systems have been installed
      in the Central Clinical Laboratory of Kyoto University Hospital. As for the
      physiological examination system, we have introduced PRINS (Physiological
      examination Result Information Network System) using an NEC computer and LAN.
      Utilizing Windows, this PRINS is connected to individual systems and equipment,
      and the data are sent to the host computer system (KING: Kyoto University
      Hospital Information Network Galaxy, which utilizes IBM). This system enabled us
      to greatly improve (1) the efficacy of examinations, (2) management and data
      stock of huge volumes, (3) rapid data analyses and simplicity in handling, and
      (4) facility of reception and reservation business. As for the sample analysis
      system, we formerly developed computer systems using MUMPS independently in the
      subdivisions. At the time of delivery system installation, we decided to unify
      them and newly establish a general managing system using MUMPS Sumitomo Electric
      Industries. The purpose of these installations are briefly as follows; (1) to
      reduce human power and to simplify delivery of samples and related business, (2)
      to report the assay results rapidly, (3) to improve and automate the quality
      controls, (4) to prevent from infections, and (5) to make handling and work
      easier. This system is comprised of biochemistry, immunology, hematology and
      emergency examination subdivisions, and connects each part in a network system
      using LAN. This is further connected to KING, the host. Actually, 4 sample
      delivery lines from 3 industries were introduced: Hitachi for biochemistry,
      Sysmex for hematology, and Toshiba-IDS for coagulation and immunology. Monitoring
      and data analyses including quality controls are performed by a host system or
      individual systems (biochemistry and hematology). At present, such heterogeneous
      installations were considered to be most suitable for our purpose and these made
      it possible to continue assays of other lines even when trouble occurred in one
      of the lines. In addition to the general systems, we have introduced various
      software programs for statistical analyses. These have been effectively utilized
      already for detailed setting of the clinical reference values for hematology
      data, and also for a computer diagnosis trial for anemia related diseases. When
      effective operations of these newly installed systems is achieved, we would like
      to extend our efforts to establish an ideal laboratory which is able to assist
      the intensive medi-care system in the university hospital.

PMID- 8569034
TI  - [Recent progress in diagnoses of diabetes and its complications].
AB  - Most of diabetics have no symptoms and chemical analyses may be sole way to
      diagnose the disease itself and its complications. Chemical analyses are also
      important to assess the propriety of glycemic control during every possible
      treatment of diabetes. Some markers for long-term glycemic control other than
      glucose concentration may be also used as a screening methods for glucose
      intolerance. HbA1c is established for long term as a marker for glycemic control
      but still large interlaboratory variation is present. Fructosamine is measured by
      a simpler procedure but many deoxidizing materials in serum especially superoxide
      may interfere with the reaction. Glycated albumin should be more reliable than
      fructosamine but a standard method of measurement has not been established yet.
      The decrease in serum 1,5-anhydro-D-glucitol(1,5-AG) is very sensitive to urinary
      glucose excretion and may be useful as a marker of glycemic control and diagnosis
      of diabetes. Discrimination of Type I(IDDM) from Type II(NIDDM) in Japanese
      diabetic patients is sometimes very difficult and evidences of autoimmunity by
      anti-glutamic acid decarboxylase(GAD) antibody and of exhaustion of insulin
      secretion by C-peptide measurement 6min after combined infusion of 1mg of
      glucagon and 20ml of 50% glucose are the few methods to diagnose. Early diagnosis
      of diabetic complication is another important point of clinico-chemical
      determinations. Usually, each diabetic complication progresses in parallel. Micro
      measurement of urinary transferrin is one of the most sensitive methods likewise
      urinary microalbumin measurement. Future measurement of advanced glycation end
      product (AGE) may also tell us if patients are suffering from diabetic
      complications or if one is suffering from diabetes or not.

PMID- 8569035
TI  - [Estimation of anti-thyroid peroxidase autoantibody (TPOAb) and anti
      thyroglobulin autoantibody (TgAb) in patients with various thyroid disease-
      comparison between histopathological findings and serological results in patients
      with Hashimoto's thyroiditis].
AB  - We compared and evaluated titers of AMC (anti-microsome antibody), and ATG (anti
      thyroglobulin antibody) by passive gelatin-agglutination and by radioimmunoassay
      in 170 sera from 129 patients with various thyroid diseases and 41 normal
      subjects. The results of conventional ATG and TgAb by RIA correlated (r = 0.731)
      and those of conventional AMC and TPOAb correlated well (r = 0.907), with
      discrepancies mostly limited to sera with low antibody titers. Five patients with
      Hashimoto's thyroiditis showed positive results in AMC, whilst negative in TPOAb.
      These sera had positive ATG autoantibody and preincubation with thyroglobulin
      inhibited the agglutination reaction of AMC tests, suggesting ATG producing false
      positive results in AMC assay. The prevalences of positive TgAb rates were higher
      than (p < 0.001) ATG in patients with Hashimoto's disease (96.6% vs 50.0%) and
      Graves' disease (76.9% vs 46.1%). However, the prevalences of positive TPOAb were
      not different from AMC (Hashimoto's disease 75.9% vs 81.0%: Graves' disease 80.8%
      vs 76.9%). In patients with Hashimoto's thyroiditis, our study demonstrates the
      results of TgAb by RIA reflects the pathological findings and the diagnostic
      sensitivity increases by using in combination with TPOAb.

PMID- 8569036
TI  - [Detection of Mycoplasma pneumoniae by using polymerase chain reaction and
      nonradioactive DNA probes].
AB  - Mycoplasma pneumoniae is the causative agent of primary atypical pneumoniae, and
      two distinct groups (I and II) have been established. Serological tests are
      relatively insensitive and the diagnosis by culture is time-consuming. This study
      was therefore undertaken to detect and to identify M. pneumoniae on culture media
      and in throat swab specimens by using polymerase chain reaction (PCR) and
      hybridization probes conjugated to alkaline phosphatase (Alp). Primer pairs were
      selected for amplification of DNA fragments in the C to D, F, G and I to J
      regions of the M. pneumoniae cytadhesin P1 genes. Amplified DNA fragments were
      visualized by staining with ethidium bromide after 2% agarose gel electrophoresis
      and by Southern hybridization with Alp-labeled probes. No amplification of the P1
      genes was seen with any of five related Mycoplasma species, the others from M.
      pneumoniae. In all of 30 clinical isolates on PPLO medium, M. pneumoniae was
      detected with the F and G primer pairs, giving 100% of sensitivity. Of 69 throat
      swab specimens, 25 were positive with the F primer pairs, and 23 positive with
      the Gen Probe test. From these results, we conclude that the PCR with F or G
      primer pairs can be adapted as a practical method for the rapid diagnosis of M.
      pneumoniae infections.

PMID- 8569037
TI  - [Studies on the mechanism of hyperfibrinolysis in liver cirrhosis--changes of
      plasma t-PA, PAI-1 and active PAI-1 levels in liver cirrhosis].
AB  - Liver cirrhosis is known to have abnormal fibrinolysis. In order to investigate
      the changes of fibrinolytic system in liver cirrhosis, plasma levels of various
      fibrinolytic molecular markers were measured in patients with different stages of
      liver cirrhosis, 20 compensated liver cirrhosis (c-LC) and 14 decompensated liver
      cirrhosis (d-LC) and were compared with those in normal subjects. Both the plasma
      levels of plasmin alpha 2-plasmin inhibitor complex (PIC) and the plasma levels
      of total fibrin/fibrinogen degradation products (T-FDP) were significantly
      elevated in patients with both c-LC and d-LC as compared with normal controls.
      Moreover, both factors in d-LC were significantly higher than those in c-LC.
      These findings indicate that patients with liver cirrhosis have
      hyperfibrinolysis. Then, in order to investigate the mechanisms of
      hyperfibrinolysis in liver cirrhosis, plasma levels of tissue-type plasminogen
      activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were
      determined in these patients. The plasma levels of t-PA significantly increased
      in both c-LC and d-LC as compared with normal controls. Its levels were higher in
      patients with LC at their decompensated stage than at their compensated stage. In
      patients with LC, plasma PAI-1 levels showed significantly higher values than
      those in normal controls. However, the plasma levels of active PAI-1 in patients
      with LC were similar to those in normal controls. These results suggest that
      hyperfibrinolysis in patients with LC is mainly due to increased concentrations
      of t-PA, without increased active PAI-1 levels.

PMID- 8569038
TI  - [An adhesion dependent injury of target cell membrane by NK cell surface
      associated metaloprotease].
AB  - Natural killer (NK) cytotoxicity was assayed with P3-X63-Ag8-U1 (P3U-1) target
      cells which had been previously demonstrated to release endogenous alkaline
      phosphatase (AlP) on the attack of lymphocyte-activated killer cells). P3U-1
      cells showed a definite sensitivity to the AlP-release test, but no response in
      the Cr-release test at all. The AlP-release was not inhibited by anti-perforin
      antibody, benzoate, phenyl-methyl-sulfonyl-fluoride, soybean trypsin inhibitor,
      Succinyl-Gly-Pro-Leu-Gly-Pro-amino-methyl-coumarin, or gamma-radiation to
      effector cells, but was inhibited by o-phenanthroline, anti-CD13 antibody, and
      anti-LFA-1 alpha antibody. The AlP-release from P3U-1, therefore, did not appear
      to be brought on by the NK cell-derived perforin, hydroxy-radical, granzymes or
      cytosolic proteases. The inhibition by o-phenanthroline and the antibody for CD13
      (aminopeptidase N) or the adhesion factor in NK cells, however, indicated that
      the membrane of such cells with adhesion ligand to NK cells was probably
      susceptible to NK cell surface-associated metaloprotease in an adhesion dependent
      manner to the extent of some injury without complete perforation through the
      membrane.

PMID- 8569039
TI  - [The clinical study on secretory leukoprotease inhibitor (SLPI) in sera of
      patients with various pulmonary diseases].
AB  - It has been reported that secretory leukoprotease inhibitor (SLPI) can be a
      useful indicator for acute respiratory tract inflammation. In the present study,
      we attempted to measure automatically the serum concentration of SLPI by enzyme
      immunoassay (EIA) in patients with various pulmonary diseases. In this automatic
      measurement of SLPI, by which the results basically well-correlate with the
      manual method, we could measure many samples easily. Serum levels of SLPI in
      patients with various pulmonary diseases were significantly higher than those in
      healthy controls (50.5 +/- 9.8ng/ml). The serum concentration of SLPI in patients
      with inflammatory lung diseases correlated with that of C-reactive protein (CRP)
      or interleukin 6 (IL-6) significantly but not strongly. These results suggest
      that SLPI may be a useful indicator for local inflammation in respiratory tract.
      The serum concentration of SLPI in patients with lung cancer (71.1 +/-
      10.8ng/ml), in particular adenocarcinoma, was significantly higher than that in
      healthy controls, but not correlated with other inflammatory markers.

PMID- 8569040
TI  - [Quantitative urine microscopic examination using disposable counting chamber for
      diagnosis of urinary tract infection].
AB  - Routine urinalysis is performed as a screening test for urinary tract infection
      (UTI) in out-patients or in-patients. We assessed the usefulness of microscopic
      examination of unspun and unstained urine using a disposable slide with counting
      chambers (Kova Slide 10 grid, Miles-Sankyo) for diagnosis of significant
      bacteriuria. 173 fresh urine samples were obtained from 173 subjects (89 male and
      84 (female), including 117 inpatients, aged from 0 to 96 years. Urine samples
      were examined for bacteriuria by the standard culture method and counting chamber
      method. Significant bacteriuria was defined as 10(5)/ml or more of bacilli for
      midstream urine and urine collected by bags and 10(4)/ml or more for urine
      collected by catheterization and from indwelling catheters. Urine leukocytes were
      also counted on disposable slide. The rapid dipstick test (N-multistix-SG-10,
      Miles-Sankyo) of leukocyte esterase activity and nitrite were measured in the
      urine specimens read by a photometer (Clinitek-10, Miles-Sankyo). Significant
      bacteriuria was diagnosed by standard culture method in 67 urine samples. Close
      correlation was obtained between bacterial counts determined by the bacterial
      culture and counting chamber method (Spearman's correlation coefficient p <
      0.001). Sensitivity and negative predictive value for significant bacteriuria
      were 94.0 and 95.1%, respectively, when bacteriuria or pyuria was present in the
      counting chamber. Dipstick test had a sensitivity and negative predictive value
      of 86.6 and 89.9%, respectively, when either leukocyte esterase activity of + or
      more, or nitrite of + was found. In out-patients, both sensitivity and negative
      predictive value were as high as 100% in counting chamber method. Thus, we can
      conclude that urine microscopy on disposable counting chambers is a very
      sensitive, simple, time-saving and lost-effective method for diagnosis of UTI.

PMID- 8569041
TI  - [Proton-magnetic resonance spectroscopy (1H-MRS) of human plasma obtained from
      patients with various cancer--new detection method for common cancer].
AB  - 1H-Magnetic Resonance (MR) Spectra of plasma obtained from patients with various
      cancer were measured. Clinical usefulness of 1H-MRS assay for detection of common
      cancer was examined. The following results were obtained. 1. High lactate peak
      was detected significantly with 1H-MR Spectra of plasma in every cancer patients.
      The patterns of 1H-MR spectra were very similar in each case, except for the
      lactate peak. 2. Lactate values (area ratio of lactate peak to TSP) of cancer
      patients showed high correlation with tumor marker of AFP, but not significant
      with CEA and CA19-9. 3. 1H-MRS assay has many advantages in the clinical
      examination. From these results, it was concluded that lactate peak in 1H-MRS
      might be useful to detect common cancer as a new tumor marker and 1H-MRS assay
      was equipped with enough characters as a new clinical laboratory assay for
      detection of specific metabolic deficiency.

PMID- 8569042
TI  - Non-radioactive mismatch analysis to detect small mutations in human hypoxanthine
      guanine phosphoribosyl transferase cDNA.
AB  - We have combined a cDNA-driven PCR technique and a non-radioactive chemical
      cleavage mismatch method, followed by a direct sequencing for detecting small
      mutations in the human hypoxanthine-guanine phosphoribosyl transferase (HPRT)
      gene. HPRT cDNA was synthesized by RT-PCR from 1,000 wild-type or HPRT(-) mutant
      cells. Wild-type cDNA was hybridized with mutant cDNA to form heteroduplexes. The
      resultant mismatched bases were modified and cleaved by base-specific chemicals,
      followed by analysis by denaturing polyacrylamide gel electrophoresis. Cleaved
      fragments were detected without using radioactive materials. Finally, direct
      sequencing of the PCR products was performed with a focus on a small limited
      region indicated by the mismatch analysis (focused sequencing). In this study,
      three small mutations in exon-3 of HPRT cDNA were detected and characterized
      completely with this system. As compared with the radioactive method, this system
      was shown to be very simple and efficient.

PMID- 8569043
TI  - Semiquantitative analysis of periodontopathogens by gene amplification.
AB  - Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, which are
      known as major causative organisms of periodontitis, were semiquantitatively
      identified by two-step polymerase chain reaction (PCR). The sets of specific
      primers for A. actinomycetemcomitans and P. gingivalis were prepared on the basis
      of the nucleotide sequences of the lktA and the fimA genes, respectively. The set
      of universal primers for eubacteria was designed from the nucleotide sequence of
      a highly conserved region in the eubacterial 16S rRNA sequence. The number of
      bacteria detectable by one-step PCR assay was no fewer than 10(3) cells. Less
      than 10(3) bacterial cells were detectable by two-step PCR assay. Subgingival
      plaque samples from 37 sites of 16 patients were obtained with paperpoints and
      analyzed by two-step PCR assay. More than 2 x 10(6) bacterial cells were found in
      the subgingival plaque samples from all diseased sites. In contrast, the number
      of total bacteria in those from more than half of healthy sites estimated by PCR
      assay was less than 2 x 10(6) cells, suggesting that subgingival plaque in
      diseased sites consists of a relatively larger number of bacteria compared with
      the population in healthy sites. While A. actinomycetemcomitans was detected in
      both healthy and diseased sites, P. gingivalis was observed only in diseased
      sites. Both periodontopathic bacteria occupied a minor part (less than 0.1%) of
      the total subgingival plaque bacteria.

PMID- 8569044
TI  - Study of hemagglutinating property of enteroinvasive Escherichia coli from
      various geographical locations.
AB  - Thirty-four strains of enteroinvasive Escherichia coli (EIEC) were examined for
      their ability to agglutinate erythrocytes from different animal species. All
      strains cultured in Casamino acid-yeast extract medium in the presence of 1 mM
      CaCl2 at 37 C for 16-22 hr induced maximal expression of hemagglutination (HA) of
      broad spectrum erythrocytes. The strongest HA was observed with guinea-pig
      erythrocytes followed by human (O type), rat, mouse, rabbit and sheep
      erythrocytes. All the strains failed to agglutinate chicken erythrocytes. HA was
      resistant to D-mannose, D-glucose, D-galactose, L-fucose, and D-fructose. Also HA
      was resistant to ethylene diamine tetraacetic acid (EDTA) and Na metaperiodic
      acid, an oxidizing agent. However, it was heat labile and completely inhibited by
      proteolytic enzymes such as proteinase K and trypsin, suggesting that the
      possible hemagglutinin of EIEC associated with the cell surface is a
      proteinaceous substance.

PMID- 8569045
TI  - Adenovirus surveillance, 1982-1993, Japan. A report of the National
      Epidemiological Surveillance of Infectious Agents in Japan.
AB  - The Infectious Agents Surveillance Center, the National Institute of Health,
      Japan, received 17,265 reports from 1982 to 1993 on cases from whom adenovirus
      was isolated or detected; 85% from 57 public health institutes and the other 15%
      from two national hospitals and two commercial diagnostic laboratories. The
      followings were found. Three major diseases caused by adenovirus were upper
      respiratory tract infection, gastroenteritis, and conjunctivitis. Patients of
      upper respiratory tract infection numbered 6,837 (40% of all patients due to
      adenovirus), the identified serotypes being in order of frequency types 3, 2, 1,
      and 5. Those of gastroenteritis numbered 1,636 (9.5%). From 40% of the
      gastroenteritis patients, adenovirus was detected by electron microscopy or
      immunochemical methods without cultivation. From the remaining 60%, virus was
      isolated in tissue culture; the serotypes of the isolates resembled those causing
      upper respiratory tract infection. Patients of conjunctivitis numbered 3,437
      (20%), the frequency being in order of types 3, 4, 8, 37, and 19. Conjunctivitis
      due to types 3 and 4 prevailed every summer; type 3 was isolated often from
      children with pharyngo-conjunctival fever and the other four types were mostly
      from adults with epidemic keratoconjunctivitis. Type 3 had a unique feature not
      seen in other types: it was most frequently isolated, causing upper respiratory
      tract infection, gastroenteritis, conjunctivitis, and pharyngo-conjunctival
      fever. Reports on isolation of type 7, which has been reported to cause severe
      pneumonia in many other countries, were as few as 28 (0.2%).

PMID- 8569046
TI  - Effects of efonidipine hydrochloride on cholesterol esterification mediated by
      beta-very low density lipoprotein in J774 macrophages.
AB  - The effects of efonidipine hydrochloride (efonidipine), a dihydropyridine calcium
      antagonist, on the cholesterol ester metabolism induced by beta-migrating very
      low density lipoprotein (beta-VLDL) in J774 macrophages were studied. The
      cholesteryl ester content in the macrophages was increased by incubation with
      beta-VLDL, and the increase was inhibited by efonidipine. Oleic acid
      incorporation into cellular cholesteryl ester was increased by beta-VLDL in J774
      macrophages. The incorporation at an early phase of beta-VLDL induction (0-3 hr)
      was inhibited by efonidipine. This inhibitory effect of efonidipine was greater
      at an early phase of beta-VLDL induction (0-3 hr) than at a late phase of the
      induction (8-11 hr). Pretreatment of the cells with efonidipine enhanced the
      inhibitory effect. Efonidipine also inhibited beta-VLDL degradation but not the
      binding and association in macrophages without pretreatment. beta-VLDL binding
      and association to macrophages were decreased by pretreatment of the cells with
      efonidipine. beta-VLDL metabolism was also decreased by dibutyryl cyclic AMP
      pretreatment. The decrease of beta-VLDL metabolism by efonidipine was prevented
      by co-treatment with efonidipine and HA1004, a protein kinase A inhibitor.
      Furthermore, efonidipine increased the intracellular cyclic AMP content in J774
      macrophages. These findings suggest that efonidipine suppresses cholesterol ester
      deposition in atherosclerotic foam cells by inhibiting the modified lipoprotein
      metabolism and cholesterol esterification mainly through elevation of the
      cellular cyclic AMP level.

PMID- 8569047
TI  - Difference among angiotensin-converting enzyme inhibitors in potentiating effects
      on bradykinin-induced microvascular leakage in guinea pig airways.
AB  - We investigated the effect of imidapril, a novel angiotensin-converting enzyme
      (ACE) inhibitor, on augmentation of airway microvascular leakage induced by
      bradykinin (BK) and substance P (SP) in guinea pigs and compared it with those of
      enalapril and captopril. The three ACE inhibitors significantly potentiated BK-
      and SP-induced airway microvascular leakage in a dose-dependent manner. In spite
      of the compatible or higher ACE inhibitory activity of imidapril, its
      potentiating activity in BK-induced leakage was lower than those of enalapril and
      captopril both by single administration (0.3-30 mg/kg, p.o.) and repeated
      administration for eight days (0.1-10 mg/kg/day, p.o.). The potentiating
      activities of the three ACE inhibitors were suppressed by pretreatment with a BK2
      receptor antagonist, but not by neurokinin 1 and neurokinin 2 antagonists,
      suggesting that neurokinins may not be involved in BK-induced leakage under the
      conditions used. On the other hand, the potentiating effect of imidapril in SP
      induced leakage was weaker than those of enalapril and captopril only after
      single high doses. The present study shows that the ACE inhibitors have different
      activity in potentiation of the airway microvascular leakage induced by BK, which
      may be ascribable to the difference in their inhibition of BK hydrolysis. This
      evidence may partly explain the smaller incidence of dry cough induced by
      imidapril compared with other ACE inhibitors when clinically used as
      antihypertensive drugs.

PMID- 8569048
TI  - Inhibitory effect of cilnidipine on pressor response to acute cold stress in
      spontaneously hypertensive rats.
AB  - We investigated the effect of cilnidipine on cardiovascular and neuroendocrine
      responses to acute cold stress in conscious and unrestrained or moderately
      restrained spontaneously hypertensive rats (SHRs). Acute cold stress
      significantly increased mean blood pressure without marked change in heart rate.
      The acute cold stress-induced elevation in blood pressure was almost abolished by
      1 mg/kg, p.o. of prazosin. The cold stress also elevated plasma norepinephrine
      and epinephrine levels. Cilnidipine at 3 mg/kg, p.o. significantly inhibited the
      pressor response to acute cold stress. Although 3 mg/kg, p.o. of nifedipine,
      nicardipine or manidipine lowered mean blood pressure to a similar extent as
      cilnidipine, none of these three drugs affected the pressor response. Cilnidipine
      also reduced the cold stress-induced increment in plasma norepinephrine but not
      the epinephrine level. These findings suggest that acute cold stress may induce
      the elevation in blood pressure due to an enhanced activation of the
      sympathoadrenal system in SHRs and that cilnidipine may suppress the pressor
      response by inhibiting the sympathetic nerve activity.

PMID- 8569049
TI  - Inhibitory effect of cilnidipine on vascular sympathetic neurotransmission and
      subsequent vasoconstriction in spontaneously hypertensive rats.
AB  - We reported previously that cilnidipine inhibited increases in blood pressure and
      plasma norepinephrine (NE) level in response to cold stress in spontaneously
      hypertensive rats (SHRs). In the present study, we investigated the effect of
      cilnidipine on sympathetic neurotransmission and subsequent vasoconstriction in
      SHRs. In pithed SHRs, electrical sympathetic nerve stimulation (ESNS) elevated
      blood pressure, and this pressor response was abolished by guanethidine.
      Cilnidipine at 10 micrograms/kg, i.v. and phentolamine at 1 mg/kg, i.v.
      suppressed the pressor response to ESNS by 28 +/- 6% and 67 +/- 3%, respectively.
      Neither nifedipine nor nicardipine inhibited it. The pressor response to
      exogenous NE was not influenced by cilnidipine. alpha, beta-Methylene ATP
      inhibited the pressor response to ESNS in the presence or absence of
      phentolamine. Cilnidipine also attenuated the phentolamine-resistant pressor
      response to ESNS. In SHR mesenteric vasculatures preloaded with [3H]-NE,
      cilnidipine (10(-7) M) as well as omega-conotoxin significantly inhibited the 3H
      overflow evoked by periarterial nerve stimulation. In radioligand binding
      experiments, cilnidipine inhibited [125I]-omega-conotoxin binding to rat
      synaptosomes, but it did not inhibit [3H]-prazosin binding to rat cortex
      membranes. These results suggest that cilnidipine may reduce electrically
      stimulated NE release from the sympathetic nerve endings of SHR vasculatures
      probably through its N-type Ca channel blocking action and that cilnidipine may
      also inhibit the vasoconstriction induced by ATP released concomitantly during
      nerve stimulation.

PMID- 8569050
TI  - Effects of folic acid and pyrimethamine, a dihydrofolate reductase inhibitor, on
      intestinal absorption of folates in rats.
AB  - Oral co-administration of folic acid (pteroylglutamic acid, PteGlu) potentiates
      the decrease of plasma 5-methyltetrahydrofolic acid (5-CH3-H4PteGlu)
      concentration induced by pyrimethamine (PYR) in rats. To clarify the mechanisms
      of this potentiated decrease, we examined the effects of PteGlu and PYR on
      intestinal absorption of folates in rat jejunum loops, because plasma 5-CH3
      H4PteGlu concentration is maintained by enterohepatic circulation of folates. The
      intestinal absorption of 5-[14C]CH3-H4PteGlu was inhibited by PteGlu, but not by
      PYR. The absorption of [3H]PteGlu was inhibited by reduced folates that exist in
      bile. These findings indicate that PteGlu competes with the bile reduced folates
      for the intestinal transport system. The bile secretion of reduced folates was
      also examined to observe the conversion of absorbed PteGlu to reduced folates in
      the liver in the presence of PYR. The bile secretion of reduced folates increased
      drastically after the administration of PteGlu alone, but not after the
      administration of PteGlu with PYR. These facts suggest that the absorbed PteGlu
      was not converted to reduced folates in the liver due to PYR. In conclusion, the
      potentiated decrease of plasma 5-CH3-H4PteGlu concentration must have resulted
      from a combination of the following two factors: the inhibition of reabsorption
      of bile reduced folates by PteGlu and the inhibition of PteGlu conversion to
      reduced folates in the liver by PYR.

PMID- 8569051
TI  - Effect of argatroban on microthrombi formation and brain damage in the rat middle
      cerebral artery thrombosis model.
AB  - Ischemic cerebral infarcts induce hypercoagulation and microthrombosis in the
      surrounding region, thus leading to vascular occlusion. We determined whether
      microthrombi contribute to the spreading of ischemic lesions following thrombotic
      middle cerebral artery (MCA) occlusion and also determined whether argatroban, a
      selective thrombin inhibitor, reduces the formation of the microthrombi and the
      area of the ischemic lesions. The rat left MCA was occluded by a platelet-rich
      thrombus formed following the photochemical reaction between rose bengal and
      green light. Microthrombi were histologically identified in the left hemisphere.
      The extent of ischemic lesions and microthrombi containing fibrin increased in a
      time-dependent manner after MCA occlusion. Argatroban inhibited the formation of
      microthrombi up to 3 hr after MCA occlusion; beyond 3 hr, it was ineffective.
      Argatroban also significantly (P < 0.01) reduced the size of ischemic cerebral
      lesions at 6 hr after MCA occlusion. It is concluded that the formation of
      microthrombi contributes to the progression of ischemic lesions in the early
      stage. It is likely that thrombin generated following thrombotic MCA occlusion
      contributes to the progression of ischemic lesions by promoting the formation of
      microthrombi. Argatroban can reduce the formation of microthrombi and ischemic
      lesions in the early stage.

PMID- 8569052
TI  - Increase in vascular sensitivity to angiotensin II and norepinephrine after four
      day infusion of 0.3 M sodium chloride in conscious kininogen-deficient brown
      Norway Katholiek rats.
AB  - Kininogen-deficient Brown Norway Katholiek (deficient BN-Ka) rats excreted a
      small amount of kinin in their urine, compared with normal BN Kitasato (normal BN
      Ki) rats from the same strain. Intraarterial (i.a.) infusion (6 ml/kg/hr) of
      conscious deficient BN-Ka rats with 0.15 M NaCl did not increase mean arterial
      blood pressure (MBP) [from 103 +/- 2 (pre) to 93 +/- 6 mmHg (day 4)] and did not
      cause sodium accumulation in the serum, cerebrospinal fluid or erythrocytes, but
      0.3 M NaCl infusion significantly increased MBP from 104 +/- 3 (pre) to 130 +/- 5
      mmHg (day 4) with increased sodium levels in the serum, cerebrospinal fluid and
      erythrocytes. Infusion of 0.3 M NaCl in normal BN-Ki rats neither increased MBP
      nor accumulated sodium. The dose-response curve of the increase in MBP for
      angiotensin II injection (i.a., bolus, 1-1000 pmol/kg) in 0.3 M NaCl-infused
      deficient BN-Ka rats shifted to the left by a factor of 10 compared with that in
      0.15 M NaCl-infused deficient BN-Ka rats, and that for norepinephrine injection
      shifted to the left by a factor of 30. Normal BN-Ki rats did not show any
      enhancement in MBP elevation with 0.3 M NaCl. These results suggest that the
      sodium accumulation attributable to a lack of kinin generation may be related to
      increased vascular reactivity to angiotensin II and norepinephrine.

PMID- 8569053
TI  - Role of the steady-state Na+ channel current in pacemaker depolarizations in
      young embryonic chick ventricular myocytes.
AB  - To assess the age-related changes in kinetic properties of the cardiac Na+
      channel, whole-cell voltage-clamp (v-c) experiments were conducted using 3-, 10-
      and 17-day-old embryonic chick ventricular heart cells. In line with the first
      order kinetic model, kinetic parameters for the activation and inactivation of
      the channel were determined from the v-c results. Simulation studies using
      kinetic parameters so determined have reproduced the current-voltage relations
      and the steady-state inactivation characteristics observed in cells in the three
      age groups. The rate of depolarization of the simulated action potentials was
      also comparable to that experimentally recorded. In conclusion, the steady-state
      Na+ conductance can play a significant role in the automatic depolarizations
      observed in young embryonic ventricular cells.

PMID- 8569054
TI  - The release and subsequent synthesis of histamine in a transfected subclone of
      rat basophilic leukemia cells that expresses human muscarinic m1 receptors.
AB  - Effects of carbachol and antigen (dinitrophenylated bovine serum albumin) on
      histamine release and histidine decarboxylase (HDC, the enzyme synthesizing
      histamine) activity were studied in 2H3-m1 cells, a subclone of rat basophilic
      leukemia cells that expresses human muscarinic m1 receptors through transfection
      with the gene. Carbachol stimulated the release of histamine and the activity of
      HDC with 30-50% the intensity of the maximal effect of the antigen. Pirenzepine,
      an m1 antagonist, inhibited these carbachol effects in a dose-dependent manner.
      The effect of the combination of carbachol and antigen on histamine release
      showed no additivity. These results indicate that these effects of carbachol are
      exerted via m1 receptors, and they suggest that the actions of carbachol and
      antigen on histamine release share a common pathway(s), and the release and
      synthesis of histamine have a positive relationship like in a feedback system.

PMID- 8569055
TI  - Metabolic effects of glibenclamide in isolated rat hepatocytes in the absence of
      extracellular Ca2+.
AB  - We examined the metabolic effects of glibenclamide, a potent second-generation
      sulfonylurea, in isolated rat hepatocytes incubated in the absence of
      extracellular Ca2+. We first demonstrated in the present study that glibenclamide
      caused a significant increase in basal glucose release and lactate production
      without any modification of intracellular Ca2+ concentration or cAMP levels in
      isolated rat hepatocytes. Furthermore, glibenclamide inhibited the noradrenaline
      induced increase in cAMP accumulation, while activation of glycogenolysis by
      noradrenaline was not suppressed by this agent. Our data indicate that
      glibenclamide exerts its metabolic effects independent of intracellular Ca2+
      mobilization and cAMP accumulation.

PMID- 8569056
TI  - Hypotensive and bradycardic effects of dl-tetrahydropalmatine mediated by
      decrease in hypothalamic serotonin release in the rat.
AB  - In anesthetized rats, intravenous administration of dl-tetrahydropalmatine (dl
      THP, 1-10 mg/kg) elicited proportional hypotension, bradycardia and decreases in
      hypothalamic serotonin (5-HT) release (measured by carbon-fiber electrodes in
      combination with voltammetry). In addition, postsynaptic blockade of 5-HT2
      receptors with cyproheptadine (2-5 mg/kg, i.v.) or ketanserin (2-5 mg/kg, i.v.)
      produced both hypotension and bradycardia, while stimulation of 5-HT2 receptors
      with 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (10-250 mg/kg, i.v.)
      produced both hypertension and tachycardia. The dl-THP-induced hypotension and
      bradycardia could be reversed by DOI treatment. The data indicate that dl-THP
      decreases both arterial pressure and heart rate through a serotonergic release
      process in the hypothalamus.

PMID- 8569057
TI  - Structure-activity relationships of alkylxanthines: alkyl chain elongation at the
      N1- or N7-position decreases cardiotonic activity in the isolated guinea pig
      heart.
AB  - Relationships between the alkyl substitutions (C1-C6) and cardiac inotropic
      activities of xanthine derivatives were studied in isolated guinea pig heart
      muscles. Most of the alkylxanthines exhibited positive inotropic activity on the
      left atrium, which was increased with an elongation of alkyl chain at the N3
      position but decreased by substitution of a long alkyl group at the N1- or N7
      position of the xanthine skeleton. Although positive inotropic activity in the
      right ventricular papillary muscle was also increased by longer alkyl groups at
      the N3-position, the inotropic activity became negative with an increment in
      alkyl chain length at the N1- or N7-position. The positive inotropic activity of
      alkylxanthines was correlated with their inhibitory activity on the
      phosphodiesterase (PDE) III isoenzyme. Adenosine A1 antagonism and PDE IV
      inhibitory activity were also partly associated with the inotropic activity
      because H-89, an inhibitor of cyclic AMP-dependent protein kinase, diminished the
      positive inotropic action and potentiated the negative inotropic action. These
      results indicate that the positive inotropic activity of alkylxanthines becomes
      weak with elongation of alkyl chains at the N1- and N7-positions; In particular,
      xanthines having two long alkyl chains show a negative inotropic activity on the
      right ventricular papillary muscle, an effect that could not be elucidated from
      their cyclic AMP-dependent action.

PMID- 8569058
TI  - Inhibition of cocaine sensitization by MK-801, a noncompetitive N-methyl-D
      aspartate (NMDA) receptor antagonist: evaluation by ambulatory activity in mice.
AB  - Alterations of cocaine effects, which were induced by prior repeated 5-time
      administration of MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten
      5,10-imine) (i.p.) alone or in combination with cocaine (s.c.) at 3- to 4-day
      intervals, were investigated by means of ambulatory activity in mice. The
      repeated administration of either cocaine (10 and 20 mg/kg) alone or MK-801 (0.3
      mg/kg) alone progressively enhanced each drug's effect. The enhanced effects of
      cocaine and MK-801 were estimated to be 1.8-2.2 times and about 1.4 times,
      respectively, as great as those at the 1st administration. Although the
      coadministration of MK-801 with cocaine produced a significant enhancement in the
      ambulation-increasing effect, the comparatively higher doses of MK-801 (0.3 and 1
      mg/kg) acted not only to reduce cocaine sensitivity but also to inhibit the
      development of cocaine sensitization. Thus, the mice that had been given MK-801
      (0.3 and 1 mg/kg) alone 5 times showed lower sensitivities to cocaine (20 mg/kg)
      than the mice given saline alone. The mice coadministered MK-801 (0.3 and 1
      mg/kg) with cocaine (10 and 20 mg/kg) also exhibited lower sensitivities to
      cocaine (10 and 20 mg/kg) than those given cocaine alone. However, MK-801 could
      not ameliorate the established sensitization to cocaine. Similar interactions
      have been demonstrated between MK-801 at 1 mg/kg, but not 0.3 mg/kg, and
      methamphetamine. The present results indicate that MK-801 can inhibit the
      development of sensitization to cocaine at a lower dose than that required to
      inhibit methamphetamine sensitization.

PMID- 8569059
TI  - Antisecretory effect of leminoprazole on histamine-stimulated gastric acid
      secretion in dogs: potent local effect.
AB  - Leminoprazole, an acid pump inhibitor, significantly reduces basal and stimulated
      gastric acid secretion in rats when administered via the systemic or local route.
      Our aim here was to characterize the antisecretory effect of leminoprazole on
      gastric acid secretion in conscious dogs. Gastric acid secretion by dogs with a
      vagally denervated Heidenhain pouch was stimulated by intravenous histamine
      infusion. Leminoprazole or omeprazole (as a reference drug) was administered
      either intravenously or locally into the pouch before or after histamine
      infusion. A bolus intravenous administration of leminoprazole and omeprazole,
      respectively, significantly and dose-relatedly inhibited the stimulated gastric
      acid secretion for > 26 hr. Local application of leminoprazole, but not
      omeprazole, significantly inhibited the acid secretion when applied for 15 to 30
      min. The duration of the local antisecretory effect observed after 30 min
      application was around 8-10 hr. The acid-degraded products of leminoprazole had
      no effect when applied to the pouch. The blood concentration of leminoprazole was
      very low at 1 hr after local application. These results indicate that
      leminoprazole suppresses the secretory function of the parietal cells of dogs,
      via both the intravenous and local routes. It remains unknown whether or not
      locally applied leminoprazole produced the acid inhibition by inhibiting the acid
      pump.

PMID- 8569060
TI  - Renal potassium channels: an overview.

PMID- 8569061
TI  - An ATP-regulated, inwardly rectifying potassium channel from rat kidney (ROMK).
AB  - With the cloning of ROMK [31] and IRK1 [32], a new family of inwardly rectifying
      K+ channels has been identified. ROMK channel isoforms are highly and
      differentially expressed in distal nephron segments of the mammalian kidney.
      These channels exhibit many of the characteristics of the low conductance, ATP
      sensitive K+ channels found in apical membranes of TAL, macula densa, and
      principal cells that are involved in potassium secretion. Thus ROMK channel
      isoforms appear to be involved in the formation of these secretory KATP channels.
      Further characterization of these channels should provide further evidence for
      their role in the secretory KATP channels and new insights into the function and
      regulation of these channels.

PMID- 8569062
TI  - Cross-talk and the role of KATP channels in the proximal tubule.
AB  - Over the last few years it has become evident that an assortment of functionally
      related, but diverse, KATP channels provide an important and physiologically
      regulated determinant of the K conductive pathways in many, if not all,
      epithelial cells expressed along the nephron. As such, KATP plays central roles
      in regulating and maintaining a number of transport processes in concert with
      physiological demands of the kidney. In the renal proximal tubule, KATP channels
      and changes in the hydrolytic activity of the Na,K-ATPase permit ATP to act as a
      coupling modulator of parallel Na,K-ATPase-K recycling. The response insures that
      cell membrane potential, intracellular K activity and cell volume are protected
      in the face of physiological variations in transcellular ion transport. In
      addition to demonstrating the physiological relevance of KATP in renal
      epithelial, these studies have provided a long awaited answer to the underlying
      mechanism of pump-leak coupling, a universal and essential homeostatic mechanism
      observed in nearly all salt translocating epithelia.

PMID- 8569063
TI  - View of K+ secretion through the apical K channel of cortical collecting duct.
AB  - The apical small-conductance K+ channel plays an important role in renal K+
      secretion, as evidenced by the presence of the extensive modulatory pathways.
      Figure 3 summarizes the current understanding of the mechanisms that modulate the
      apical small-conductance K+ channel. Stimulation of adenylate cyclase enhances
      channel activity and consequently K+ secretion. In contrast, increases in
      intracellular Ca2+ concentration and activation of Ca(2+)-dependent signal
      transduction pathways inhibit the K+ channel and thus decrease K+ secretion. The
      vasopressin-induced stimulation of K+ secretion in CCD results at least in part
      from cAMP-dependent signal transduction pathways. The Ca(2+)-dependent signal
      transduction pathway is responsible for modulatory coupling between Na+ pump
      turnover and apical K+ conductance when the Na+ pump is inhibited.

PMID- 8569064
TI  - Molecular characterization of voltage and cyclic nucleotide-gated potassium
      channels in kidney.

PMID- 8569065
TI  - K+ channels in the basolateral membrane of rat cortical collecting duct.

PMID- 8569066
TI  - Purification and characterization of epithelial Ca(2+)-activated K+ channels.
AB  - Reabsorption of NaCl in the thick ascending limb of Henle's loop in the kidney
      and in the surface cells in the distal colon involves the integrated function of
      several membrane transport systems including ion channels, the Na,K,Cl
      cotransport system and the Na,K-pump. To determine if their properties are
      consistent with a role in regulation of transepithelial transport, Ca(2+)
      activated K+ channels from the luminal membrane of the TAL cells and from the
      basolateral membrane of the distal colon cells have been characterized by flux
      studies in plasma membrane vesicle preparations and by single channel
      measurements in lipid bilayers. The channels are found to be activated by Ca2+ in
      the physiological range of concentration with a strong dependence on
      intracellular pH and the membrane potential. The Ca(2+)-sensitivity of the K+
      channels is modulated by phosphorylation and dephosphorylation and the K+ channel
      protein must be in a phosphorylated state to respond to intracellular
      concentrations of Ca2+. As a step towards purification of the K+ channel
      proteins, procedures for solubilization and reconstitution of the K+ channels
      have been developed. The observation that the epithelial Ca(2+)-activated K+
      channels bind calmodulin in the presence of Ca2+ have allowed for partial
      purification of the K+ channel proteins by calmodulin affinity chromatography. In
      the sequences for the two cloned Ca(2+)-activated K+ channels, the mSlo channel
      and the slowpoke channel, putative calmodulin binding regions can be identified.

PMID- 8569067
TI  - The aquaporin family of water channels in kidney.
AB  - The longstanding puzzle of membrane water permeability was advanced by the
      discovery of channel-forming integral protein (CHIP). This protein was shown to
      function as a water channel when expressed in Xenopus oocytes or when
      reconstituted into synthetic membranes. Site-directed mutagenesis and electron
      crystallography reveal tetrameric organization of CHIP, and the two halves of
      CHIP are tandem repeats folded into an obversely symmetric structure which
      resembles an hourglass. Each tetramer is comprised of functionally independent
      subunits. CHIP is the archetypal member of a newly-recognized family of membrane
      water transporters known as the "Aquaporins" (AQPs). AQP1 (CHIP) is abundant in
      the apical and basolateral membranes of renal proximal tubules and descending
      thin limbs, and is also present in a number of extra renal tissues. In the
      collecting duct, AQP2 is the predominant vasopressin-sensitive water channel.
      AQP2 is localized in the apical membrane and in intracellular vesicles which are
      targeted to the apical plasma membranes when stimulated by antidiuretic hormone.
      Humans are identified with mutations in AQP1 and AQP2 and exhibit contrasting
      clinical phenotypes. AQP3 resides in the basolateral membranes of collecting duct
      principal cells providing an exit pathway for water, and AQP4 is abundant in
      brain, where it apparently functions as the hypothalamic osmoreceptor responsible
      for secretion of antidiuretic hormone. Continued analysis of the aquaporins is
      providing detailed molecular insight into the fundamental physiological problems
      of water balance and water balance disorders.

PMID- 8569069
TI  - Water channels in the kidney collecting duct.

PMID- 8569068
TI  - Structure and function of kidney water channels.
AB  - There is now firm evidence that water transporting proteins are expressed in
      renal and extrarenal tissues. In the kidney, proximal-type (CHIP28) and
      collecting duct (WCH-CD) water channels have been identified. We have cloned
      three kidney cDNAs with homology to the water channel (aquaporin) family,
      including a mercurial-insensitive water channel (MIWC), and a glycerol
      transporting protein (GLIP) in collecting duct basolateral membrane. To elucidate
      water transporting mechanisms, a series of molecular and spectroscopic studies
      were carried out on purified CHIP28 protein and expressed chimeric and mutated
      CHIP28 cDNAs. The results indicate that CHIP28 transports water selectively, that
      CHIP28 monomers are assembled in membranes as tetramers, but that individual
      monomers function independently. Monomers contain multiple membrane-spanning
      helical domains. Based on these data and recent electron crystallography results,
      a model for water transport is proposed in which water moves through narrow pores
      located within individual CHIP28 monomers.

PMID- 8569070
TI  - Molecular mechanisms for the regulation of water transport in amphibian epithelia
      by antidiuretic hormone.

PMID- 8569071
TI  - Identification and localization of calcium channel alpha 1 and beta subunit
      isoforms in the kidney.

PMID- 8569072
TI  - Calcium transport in rabbit distal cells.

PMID- 8569073
TI  - Molecular biology of calcium channels.
AB  - Pharmacological and electrophysiological studies have established that there are
      multiple types of voltage-gated Ca2+ channels. Molecular biology has uncovered an
      even greater number of channel molecules. Thus, the molecular diversity of Ca2+
      channels has its basis in the expression of many alpha 1 and beta genes, and also
      in the splice variants produced from these genes. This ability to mix and match
      subunits provides the cell with yet another mechanism to control the influx of
      calcium. Future studies will describe new subunits, the subunit composition of
      each type of channel, and the cloning of new Ca2+ channel types.

PMID- 8569074
TI  - The renal cGMP-gated cation channel: its molecular structure and physiological
      role.
AB  - Cyclic nucleotide-gated cation channels, which are permeable to monovalent and
      divalent cations, are expressed in a number of tissues. cDNAs encoding cGMP-gated
      cation channel subunits have been cloned in retinal rods, cones, olfactory
      neuroepithelium, pineal gland, aorta, testis, heart, and most recently kidney.
      Patch clamp studies have identified and characterized cGMP-gated cation channels
      in the cortical collecting duct (CCD) and inner medullary collecting duct (IMCD).
      cGMP-gated cation channels in kidney share many biophysical and molecular
      properties with the retinal rod cGMP-gated channel. However, unlike the retinal
      rod channel, the cGMP-gated cation channel in kidney is inhibited by cGMP and
      stimulated by increased calcium levels. In the IMCD the cGMP-gated cation channel
      mediates electrogenic sodium absorption which is inhibited by ANP via cGMP.
      Recently, cGMP-gated cation channel poly(A+) RNA has been identified in other
      nephron segments by RT-PCR and in situ PCR hybridization. Furthermore, cGMP-gated
      cation channel protein has also been identified in all nephron segments by
      Western blot analysis. These observations suggest that cGMP-gated cation
      channels, or closely related gene products, may play an important physiological
      role in all nephron segments. Hormones that increase intracellular cGMP may
      regulate sodium, and perhaps calcium, uptake in nephron segments proximal to the
      IMCD. Increases in cell sodium and calcium may regulate other transport and
      signaling pathways.

PMID- 8569075
TI  - Stretch-activated ion channels.

PMID- 8569076
TI  - The connexin family of intercellular channel forming proteins.

PMID- 8569077
TI  - Role of growth factors in mesangial cell ion channel regulation.
AB  - Our single channel work has characterized two ion channels capable of
      depolarizing mesangial cells and activating classic, voltage-activated Ca2+
      channels in response to growth-stimulatory peptides (such as Ang II, ET and
      insulin): (1) Ca(2+)-dependent, 4 pS Cl- channel promoting Cl- efflux; and (2)
      Ca(2+)-dependent, 27 pS nonselective cation channels promoting cation influx. We
      have also characterized a third channel which provides an alternative, receptor
      operated pathway for Ca2+ entry in response to the growth factor, PDGF: (3)
      Ca(2+)-permeable, 1 pS cation channel. Consistent with our model of mesangial
      cell signal transduction (Fig. 1), these three mesangial cell ion channels are
      activated by binding of growth factors to membrane receptors (Fig. 8). Defective
      channel regulation, such as occurs in early diabetes mellitus, would promote
      mesangial cell relaxation and pathogenic glomerular hyperfiltration. Glomerular
      hyperfiltration and hypertension have been proposed to be major pathogenic
      factors in renal disease progression [4, 29, 38, 39]. Compensatory renal growth
      factor responses initially provide adaptive changes in glomerular hemodynamics
      after loss of functional renal mass. However, chronic stimulation of these
      mesangial cell ion channels by renal growth factors would promote sustained
      extracellular Ca2+ entry, resulting in mesangial cell contraction and growth, and
      progressive decreases in Kf and GFR. Eventually, this process leads to
      irreversible renal damage due to the development of glomerulosclerosis and
      interstitial fibrosis.

PMID- 8569078
TI  - Effects of phosphorylation on ion channel function.
AB  - A fundamental property of ion channels is their ability to be modulated by
      intracellular second messenger systems acting via covalent modifications of the
      channel protein itself. One such important biochemical reaction is
      phosphorylation on serine, threonine, and tyrosine residues. Ion channels in the
      kidney are no exception. Moreover, many ion channels, including many amiloride
      sensitive epithelial Na+ channels, are subject to modulation by a multiplicity of
      inputs. For example, renal Na+ channels are not gated by voltage in their
      unphosphorylated state. However, upon phosphorylation by PKA plus ATP, these
      channels become voltage-dependent as well as having their open probability
      increased. Phosphorylation by PKC inhibits channel activity regardless of whether
      the channel was previously phosphorylated by PKA. Likewise, Na+ channel ADP
      ribosylation by PTX overrides the actions of cAMP-dependent phosphorylation.
      Consistent with this idea is the fact that the phosphorylation sites for PKA and
      PKC and the ADP-ribosylation sites occur on different polypeptides comprising the
      channel complex. Epithelial Na+ channel activity is also regulated by
      methylation, arachidonic acid metabolites, and by interactions with cytoskeletal
      components. An exciting new age in understanding renal Na+ channel function has
      begun. Canessa and collaborators [103, 104] and Lingueglia et al [105] have, for
      the first time, identified by expression cloning an amiloride-sensitive Na+
      channel from rat distal colon. The messenger RNA encoding the subunits comprising
      this channel are expressed in the distal tubule and cortical collecting tubule of
      the kidney (Rossier, unpublished observations). In addition, our laboratory has
      successfully cloned a mammalian homologue of this same channel from bovine renal
      papillary collecting ducts [106].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8569079
TI  - Molecular genetics of ion channel diseases.
AB  - Many physiological processes depend upon the proper functioning of plasma
      membrane ion channels. This is most apparent in absorptive and secretory
      epithelia, and in electrically excitable tissues such as nerve and muscle.
      Disturbances in the operation of ion channels in these settings can alter normal
      physiology and cause disease. This review illustrates the use of molecular
      genetics in identifying hereditary diseases caused by mutations in genes which
      encode various skeletal muscle ion channels. Recent advances in the discovery of
      genetic mutations in the skeletal muscle voltage-gated sodium channel in certain
      forms of periodic paralysis, mutations in the skeletal muscle chloride channel
      gene in myotonia congenita, and defects in two distinct calcium channels that
      underlie disorders of excitation-contraction coupling (murine muscular
      dysgenesis, malignant hyperthermia susceptibility) will be presented. In each
      case, prior knowledge of abnormal ion channel function prompted the search for
      mutations in candidate genes. This work is beginning to shed new light on the
      relationship between ion channel structure and function by studies of naturally
      occurring channel mutations.

PMID- 8569080
TI  - Cross-talk between sodium and potassium channels in tight epithelia.

PMID- 8569081
TI  - Properties and regulation of ion channels in MDCK cells.
AB  - The MDCK cell has proven to be a useful model cell line for the study of
      properties and regulation of renal epithelial ion channels. Patch clamp studies
      disclosed the existence of several K+ channels and of a Cl- channel, and their
      regulation by hormones, cell volume, trace elements and drugs. Most hormones
      affect K+ channels at least in part by increasing cytosolic Ca2+. However,
      indirect evidence points to additional mechanisms contributing to K+ channel
      activation. Cell swelling activates both K+ channels and unselective anion
      channels. ICln, a protein cloned from MDCK cells, is either a Cl- channel or a
      regulator of thereof. ICln is up-regulated by cellular acidification and is
      crucial for rapid regulatory cell volume decrease.

PMID- 8569082
TI  - Expression of NHE-3 in the apical membrane of rat renal proximal tubule and thick
      ascending limb.
AB  - Apical membrane Na/H exchange is a principal mechanism of renal proximal tubule
      Na absorption and H secretion, and thick ascending limb H secretion. Based on
      current data on Na/H exchanger isoforms (NHE-1 to 5), NHE-3 is the likeliest
      candidate for the apical membrane isoform. The present study localizes NHE-3 in
      rat kidney using polyclonal antisera against cytoplasmic epitopes of rat NHE-3.
      These antisera recognized an approximately 87 kD protein in Na/H exchanger
      deficient cells transfected with the rat NHE-3 gene but not in mock-transfected
      cells. All antisera labeled an approximately 87 kD protein in plasma membranes
      from cortex and outer medulla. Fractionation of cortical membranes showed
      labeling in apical but not basolateral membranes. Cross linking studies suggested
      existence of oligomeric forms of the transporter. Immunohistochemistry showed
      strong staining of the apical membrane of S1 convoluted, and S2 convoluted tubule
      with lesser staining of the S2 straight tubule and absent staining of S3. Weak
      staining was observed in thin descending limbs in the inner stripe and intense
      staining was seen in the apical membrane of medullary and cortical thick
      ascending limbs. NHE-3 staining was absent in the remainder of the nephron. In
      summary, NHE-3 is the isoform responsible for NaCl and NaHCO3 absorption in the
      proximal convoluted tubule, and NaHCO absorption in the thick ascending limb. In
      the S3 proximal tubule and the distal convoluted tubule, apical membrane Na/H
      exchange activity is likely mediated by other isoform(s) of the NHE family.

PMID- 8569083
TI  - SPARC gene expression is reduced in early diabetes-related kidney growth.
AB  - Renal enlargement is a characteristic feature of diabetes in humans and
      experimental animals that may predict subsequent renal disease. The biological
      processes involved in diabetes-related kidney growth are complex and involve
      changes in extracellular matrix, cell hypertrophy and hyperplasia. Secreted
      protein acidic and rich in cysteine (SPARC) is an extracellular matrix protein
      with anti-adhesive, antiproliferative and matrix remodeling properties. We
      examined kidney SPARC gene expression and protein content in early experimental
      diabetes. By Northern blot analysis, kidney SPARC mRNA fell in diabetic animals
      at day 1 to 40 +/- 15% of controls levels (mean +/- SEM, P < 0.01) to 42% +/- 11%
      on day 3 (P < 0.01) with a further decrease at day 7 to 29 +/- 7% (P < 0.001). In
      situ hybridization demonstrated SPARC mRNA within glomeruli renal interstitial
      cells and in blood vessels but not in tubular epithelial cells. SPARC mRNA was
      decreased in diabetic rats within a change in the pattern of distribution. By
      immunofluorescence, SPARC protein was detected in glomeruli and tubular basement
      membrane. Diabetes was associated with a decrease in SPARC protein at both sites.
      These data demonstrate that the onset of diabetes-related kidney growth is
      associated with a reduction in SPARC mRNA and protein. In the context of the
      known biological actions of SPARC, the findings in the present study implicate
      this matrix protein in the pathogenesis of diabetes related kidney growth.

PMID- 8569084
TI  - Renal uptake of an 18-mer phosphorothioate oligonucleotide.
AB  - Renal uptake of a 35S labeled 18-mer phosphorothioate oligodeoxynucleotide
      (molecular wt approximately 6,000) was evaluated following intravenous infusion
      into rats. The kidneys contained 21 +/- 3% of the infused dose at five hours
      after infusion and 3 +/- 1% of the infused dose at four days after infusion. The
      concentration of oligonucleotide was greater in the kidney than in the liver,
      spleen, or plasma at both intervals. Urine excretion of oligonucleotide label
      averaged 17 +/- 1%, 35 +/- 5%, and 64 +/- 3% of the infused dose at five hours,
      one day, and four days after infusion. Electrophoresis (PAGE) showed that
      oligonucleotide was retained in the kidney was the intact 18-mer at both five
      hours and four days after infusion, while full size oligonucleotide was not found
      in the urine at either interval. Light microscopic autoradiography showed that
      oligonucleotide uptake was most prominent in the early proximal tubule. Electron
      microscopic autoradiography indicated that oligonucleotide was not confined to
      the brush border or endocytic-lysosomal pathway. Micropuncture studies showed
      that the tubule fluid to plasma concentration ratios of oligonucleotide label
      averaged 7 +/- 3% in Bowman's space and 6 +/- 2% in the distal tubule. Despite
      restriction of filtration by plasma protein binding, as indicated by the low
      Bowman's space to plasma concentration ratio, the calculated tubular reabsorption
      rate for oligonucleotide was sufficient to account for the large amount of
      oligonucleotide found in the kidney after intravenous infusion. These results
      indicate that the proximal tubule plays a prominent role in the disposition of
      intravenously infused oligonucleotide, and raise the possibility that
      oligonucleotides could exert antisense effects in this nephron segment.

PMID- 8569085
TI  - Role of angiotensin II in the expression and regulation of transforming growth
      factor-beta in obstructive nephropathy.
AB  - Unilateral ureteral obstruction (UUO) leads to fibrosis of the obstructed kidney.
      We tested the hypothesis that interstitial fibrosis in UUO results, at least in
      part, from enhanced expression of transforming growth factor-beta (TGF-beta)
      which in turn is regulated by local angiotensin II (Ang II) generation. (The
      generic name TGF-beta is used to discuss properties shared by all isoforms, but
      special reference to other isoforms is made when specifically needed.) Using
      Northern blot and immunohistochemical analysis, we examined the expression of TGF
      beta in rat kidneys after 24 hours (aUUO) and one week (cUUO) of obstruction.
      Obstructed kidneys from both periods had increased interstitial and perivascular
      TGF-beta immunoreactivity compared to contralateral and sham kidneys, in which
      immunostaining was confined to the inner medulla. Relative abundance of all TGF
      beta mRNA isoforms were higher in the obstructed than in contralateral and sham
      kidneys in both aUUO and cUUO. Expression of TGF-beta isoforms varied according
      to site (cortex vs. medulla), segment of the nephron, type of cells and duration
      of the obstruction. The increase in TGF-beta immunoreactivity and mRNA levels in
      aUUO and cUUO was almost totally abolished by pretreatment with losartan. We
      conclude that in UUO: (a) TGF-beta gene expression is increased and
      differentially regulated; (b) Ang II, at least partially, mediates the
      overexpression of TGF-beta gene; and (c) Ang II may play a central role in
      fibrogenesis in this and other models of tubulointerstitial disease.

PMID- 8569086
TI  - Sequential changes in renal expression of renin-angiotensin system genes in acute
      unilateral ureteral obstruction.
AB  - Unilateral ureteral obstruction (UUO) alters the expression of genes encoding for
      the renin-angiotensin system (RAS). We tested the hypothesis that changes in RAS
      genes expression occur soon after obstruction. Indeed, measurements during the
      first 24 hours of UUO showed up-regulation of renin mRNA in the obstructed kidney
      at 1 hour. UUO also led to increases in PRA and renal renin content, ACE activity
      and Ang II concentration in the experimental kidney. The obstructed kidney
      relative abundance of renin mRNA was increased compared to basal at 1, 2, 6, and
      24 hours; the contralateral kidney renin mRNA expression was reduced. AT1-R mRNA
      expression was diminished at 6 and 24 hours in the obstructed kidney compared to
      contralateral and sham kidneys. ACE activity was up-regulated in the obstructed
      kidney and transiently down-regulated in the contralateral kidney. These findings
      show for the first time that activation of the RAS results from as little as 1
      hour of UUO and that up-regulation of renin mRNA and ACE activity lead to
      increase Ang II production which down-regulates AT1-R mRNA as early as 6 hours
      post-UUO. These studies establish a pattern of sequential, differential
      regulation of the RAS genes in acute UUO that provide an explanation for the
      hemodynamic changes in this condition.

PMID- 8569087
TI  - Low-density lipoprotein stimulates the expression of macrophage colony
      stimulating factor in glomerular mesangial cells.
AB  - Disordered lipoprotein metabolism and the enhanced influx and accumulation of
      circulating mononuclear leukocytes into vascular tissue are common
      pathobiological phenomena associated with both atherosclerosis and
      glomerulosclerosis. Since atherogenic lipoproteins (such as low density
      lipoprotein, LDL) have been implicated in monocyte migration and proliferation
      into the glomerular mesangium, we examined the effect of LDL on mesangial cell
      expression of macrophage colony-stimulating factor (M-CSF), a cytoregulatory
      peptide associated with monocyte chemoattraction, differentiation and
      proliferation. Mesangial cell M-CSF gene expression, protein synthesis and
      secretion, and its biological activity to induce progenitor colony formation and
      monocyte proliferation were studied in murine mesangial cells. Incubation of
      either primary cultures or SV-40 transformed murine mesangial cells with LDL (0
      to 200 micrograms/ml) induced M-CSF steady-state mRNA expression, in a dose
      dependent manner (52 to 183% of control) when Northern blots were analyzed
      quantitatively by densitometric scanning. Similarly, Western blot analysis showed
      that LDL-activated SV-40 transformed mesangial cells increased M-CSF protein
      synthesis and secretion in a dose-dependent manner. The conditioned media
      obtained by incubating mesangial cells with LDL induced bone marrow progenitor
      colony formation that could be inhibited by specific neutralizing antibodies
      against murine M-CSF. Finally, the biological activity of M-CSF secreted by LDL
      activated mesangial cells was further confirmed by its enhanced ability to induce
      monocyte proliferation. These data indicate that LDL, by activating mesangial
      cells to induce M-CSF and possibly other monocyte chemoattractants, may regulate
      the migration and proliferation of cells of mononuclear leukocytic origin into
      the mesangium supporting a pathobiological role for LDL in glomerular injury.

PMID- 8569088
TI  - Activation of nuclear factor-kappa B correlates with MCP-1 expression by human
      mesangial cells.
AB  - Emerging evidence suggests that mesangial cell-derived monocyte chemoattractant
      protein-1 (MCP-1) is a potentially important mediator of glomerular monocyte
      infiltration. Interleukin-1 beta (IL-1) has been found in glomeruli during
      inflammation, and is a potent inducer of MCP-1 expression by mesangial cells.
      Analysis of the promoter region of the human MCP-1 gene demonstrates several
      putative binding sites for transcription activating factors, including
      recognition elements for the IL-1-inducible transcription factor, nuclear factor
      kappa B (NF-kappa B). This study investigated the role of NF-kappa B in IL-1
      induced MCP-1 expression by human mesangial cells. We found that treating
      mesangial cells with IL-1 resulted in the rapid activation (within 30 min) and
      nuclear translocation of NF-kappa B. NF-kappa B activation could be blocked by
      preventing the proteolytic degradation of I kappa B, the cytoplasmic inhibitor of
      NF-kappa B, with the protease inhibitor tosyl-phe-chloromethylketone (TPCK).
      Inhibition of NF-kappa B with TPCK correlated with a dose-dependent reduction in
      IL-1-induced MCP-1 mRNA levels. Conversely, raising intracellular cyclic-AMP
      levels, or exposing mesangial cells to herbimycin A, treatments that block IL-1
      induced MCP-1 mRNA expression, significantly attenuated NF-kappa B activation.
      Finally, blocking the synthesis of one of the protein subunits of NF-kappa B with
      an antisense oligonucleotide decreased MCP-1 mRNA levels in response to IL-1.
      These data suggest that MCP-1 gene transcription may be mediated, in part, by the
      transcription factor NF-kappa B.

PMID- 8569089
TI  - Acute changes in urinary excretion of nitrite + nitrate do not necessarily
      predict renal vascular NO production.
AB  - NO2 + NO3 (NOx), the stable oxidation products of NO, and cGMP are widely
      accepted as indices of in vivo NO production. Whether acute changes in urinary
      excretion of nitrite + nitrate (UNOXV) can be taken to reflect acute changes in
      renal and/or systemic NO production is not known. The present studies were
      conducted in the conscious rat to investigate the effect on acute changes in
      UNOxV, of maneuvers that (a) enhance NO production and (b) act as diuretics. L
      arginine (L-arg) and acetylcholine (Ach) produce equivalent NO dependent falls in
      renal vascular resistance (RVR), but a much greater increase in UNOX V is seen
      with L-arg. D-arg does not stimulate NO and has no renal vasodilatory effect, but
      produces a large rise in UNOX V, and SNP lowers BP but not RVR and results in a
      reduced UNOX V. None of the diuretics employed should stimulate the NO system or
      lower RVR; however, the proximally acting agents, acetazolamide and D-arg
      increased UNOx V, while the loop diuretic furosemide had little effect. H2O
      diuresis (a distal event) led to a fall in UNOx V. These data suggest that NOx is
      reabsorbed extensively in the proximal tubule and that inhibition of proximal
      reabsorption leads to an increase in UNOx V. Also, our results show that the
      relationship between UNOx V and UcGMP V is unpredictable. Therefore, we conclude
      that measurements of acute changes in UNOxV and/or UcGMP V should be interpreted
      cautiously, since they may reflect altered tubular handling of NOx rather than
      the acute activity of the systemic and/or renal NO systems.

PMID- 8569090
TI  - Rat mesangial cells in vitro synthesize a spectrum of proteoglycan species
      including those of the basement membrane and interstitium.
AB  - Accumulation of extracellular matrix within the mesangium is an important event
      in the development of glomerular disease. In this report we have used indirect
      immunofluorescence to positively identify a number of constituents of the
      mesangial matrix synthesized by rat mesangial cells (RMC) in vitro including
      laminin, fibronectin, type IV collagen and the basement membrane heparan sulphate
      proteoglycan (BM-HSPG) known as perlecan. In addition, using Mab 2B5 we
      demonstrate that RMC synthesize a specific basement membrane chondroitin sulfate
      (BM-CSPG), a matrix component that in normal animals is localized in the
      mesangium but is not found in the pericapillary glomerular basement membrane
      (GBM). Further characterization of the proteoglycans synthesized by RMC in vitro
      revealed: (i) a second large CSPG, identified as versican; (ii) two small
      dermatan sulphate proteoglycans identified as biglycan and decorin, which
      together account for the majority of the proteoglycans; (iii) a large HSPG-I,
      probably related to perlecan; and (iv) a small HSPG-II. The cell layer
      proteoglycans can be sub-divided into a class that are probably free in the
      membrane, and a class of anchored molecules of the extracellular matrix or
      stabilized by cytoskeletal elements.

PMID- 8569091
TI  - Endothelin-1 and endothelin B type receptor are induced in mesangial
      proliferative nephritis in the rat.
AB  - We studied whether endothelin-1 (ET-1) and its receptor subtypes (ETAR,
      endothelin A type receptor; and ETBR, B type receptor) were up-regulated in the
      glomerulus of a rat model of mesangial proliferative glomerulonephritis induced
      by anti-thymocyte serum (anti-Thy-1 GN). A marked increase in preproET-1 mRNA
      could be demonstrated in glomerular RNA 3 and six days after disease induction
      (4.1- and 4.9-fold vs. day 0, respectively), corresponding to the time of
      mesangial cell proliferation, to the time of macrophage infiltration into
      glomeruli, and also to the time of increase in glomerular PDGF B-chain mRNA
      expression. The localization of ET-1 protein in the mesangial area and along the
      inner aspect of the glomerular capillary wall was also demonstrated by
      immunohistochemistry from day 3 and maximal at day 6. The major source of the
      cells expressing ET-1 in glomeruli appeared to be mesangial cells, glomerular
      endothelial cells and monocyte/macrophages. Furthermore, both gene and protein
      expression of ET-1 were associated with increased urinary excretion of ET-1.
      There was no increase in the plasma ET-1 immunoreactivity. Glomerular expression
      of ETBR mRNA increased in anti-Thy-1 GN (1.5-fold vs. day 0 at day 3 after
      disease induction, 3.6-fold at day 6 and 2.7-fold at day 10), but there was
      minimal change in ETAR mRNA expression. These results suggest that preproET-1
      mRNA, which is induced in anti-Thy-1 GN, is linked primarily with ETBR mRNA
      expression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8569092
TI  - Induction of heme oxygenase in toxic renal injury: a protective role in cisplatin
      nephrotoxicity in the rat.
AB  - Cellular content of heme is regulated by heme oxygenase, the rate limiting enzyme
      in the degradation of heme. Induction of heme oxygenase is a protective response
      in an in vivo model of heme protein mediated renal injury, the glycerol model of
      acute renal failure. In addition to heme, heme oxygenase is induced by diverse
      forms of oxidative stress, the functional significance of which is currently
      unknown. We examined whether heme oxygenase is induced, and the functional
      significance of such induction, in two in vivo models of oxidant-induced toxic
      nephropathy, namely, cisplatin and gentamicin nephropathies; nephrotoxicity in
      these models is not dependent on the delivery of a burden of heme proteins to the
      kidney as occurs in the glycerol model. We demonstrate induction of heme
      oxygenase mRNA and protein in the kidney as early as 6 and 12 hours after a
      single dose of cisplatin (6 mg/kg i.v.). Pretreatment with tin protoporphyrin, a
      competitive inhibitor of heme oxygenase, led to higher serum creatinine values on
      days 3 through 5 and lower inulin clearances on day 5; tin protoporphyrin also
      exacerbated renal injury in this model. Renal hemodynamics studied at day 2 after
      cisplatin demonstrate reduced renal blood flow rates, increased renal vascular
      resistance and increased fractional excretion of sodium in rats treated with tin
      protoporphyrin. Tin protoporphyrin alone had no significant effect on serum
      creatinine and renal hemodynamics in rats with intact, disease-free kidneys. We
      confirmed that tin protoporphyrin prevented the increase in heme oxygenase
      activity induced by cisplatin. Induction of heme oxygenase by cisplatin was
      associated with increased kidney heme content and ferritin content.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8569093
TI  - Postischemic injury, delayed function and Na+/K(+)-ATPase distribution in the
      transplanted kidney.
AB  - We evaluated the postischemic renal injury in 22 patients undergoing renal
      transplantation. Renal tissue obtained 45 to 60 minutes after reperfusion of the
      allograft was stained with specific antibodies against the delta subunit of
      Na+/K(+)-ATPase, fodrin and ankyrin. The distribution of each cytoskeletal
      protein was analyzed by laser confocal microscopy. Subsequent allograft function
      was assessed on two occasions, 1 to 3 and 36 hours post-reperfusion,
      respectively. Recipients were divided into two groups: those who achieved a
      normal GFR on post-transplant day 3 (group 1, N = 12) and those with persistent
      hypofiltration (group 2, N = 10). Patients of both groups exhibited impaired
      sodium reabsorption and isosthenuria one to three hours postoperatively, but
      these abnormalities persisted on day 3 only in group 2 subjects with persistent
      hypofiltration. Abnormalities of Na+/K(+)-ATPase, ankyrin and fodrin were
      confined to proximal tubule cells and were marked only in the subjects of group
      2. They consisted of redistribution of each cytoskeletal protein from the
      basolateral membrane to the cytoplasm. We conclude that postischemic injury to a
      renal allograft results in a loss of polarity of proximal tubule cells. We
      propose that ensuing impairment of proximal sodium reabsorption could activate
      tubuloglomerular feedback, thereby contributing to the protracted hypofiltration
      that characterizes this form of postischemic, acute renal failure.

PMID- 8569094
TI  - High diagnostic performance of CT scan for analgesic nephropathy in patients with
      incipient to severe renal failure.
AB  - Recently, well performing diagnostic criteria for analgesic nephropathy in end
      stage renal failure (ESRF) patients were defined by the demonstration of a
      bilateral decrease in renal volume combined with either bumpy contours or
      papillary calcifications. In this study, the diagnostic value of computed
      tomography (CT) scan was compared to the previously used renal imaging techniques
      (sonography and conventional tomography). In a first study, a cohort of 40
      analgesic abusers (defined as daily use of analgesic mixtures during at least 5
      years) and 40 controls, all ESRF patients without a clear renal diagnosis, were
      investigated with sonography, tomography and CT scan without injection of
      iodinated contrast material, to search for the imaging signs of analgesic
      nephropathy. Using CT scan, sonography and tomography, renal size could be
      evaluated with comparable results while CT scan was superior in the detection of
      papillary calcifications (sensitivity 87%, specificity 97%). In a second
      controlled study of 53 analgesic abusers with a serum creatinine between 1.5 to 4
      mg/dl in the absence of a clear renal diagnosis, a CT scan was performed and
      scored for the presence of decreased renal volume, bumpy contours and papillary
      calcifications. It was found that the renal image of analgesic nephropathy on CT
      scan in an early stage of renal failure is comparable with the observations made
      in ESRF patients. Particularly the demonstration of papillary calcifications
      showed a high sensitivity of 92% with a specificity of 100% for the early
      diagnosis of analgesic nephropathy.

PMID- 8569095
TI  - Impaired agonist-induced calcium signaling in hepatocytes from chronic renal
      failure rats.
AB  - Some hormones exert their action by inducing a rise in cytosolic calcium [Ca2+]i
      (calcium signal), and therefore, a blunting in hormone-induced calcium signal
      would engender resistance to the action of the hormone. Chronic renal failure
      (CRF) is associated with resistance to the action of a variety of hormones, a
      rise in [Ca2+]i and decrease in the amount of mRNA of one hormone receptor, the
      PTH-PTHrP receptor. We examined the calcium-signal induced by PTH, angiotensin
      II, vasopressin and glucagon in hepatocytes from CRF animals, evaluated the
      effect of the basal level [Ca2+]i on the calcium signal and explored the effect
      of [Ca2+]i on the mRNA of the receptors of these agonists. Hepatocytes from CRF
      rats have elevated basal levels of [Ca2+]i and display significantly reduced
      calcium signals induced by all these hormones, while the calcium signals were
      normal in PTX-CRF animals and those treated with verapamil both of which have
      normal levels of [Ca2+]i despite CRF. The calcium signals induced by dibutyryl
      cyclic AMP and G protein activator (GTP gamma S) were normal in hepatocytes from
      CRF animals despite the high levels of [Ca2+]i. Northern blotting experiments
      revealed that the levels of the mRNA of the receptors of PTH-PTHrP, angiotensin
      II and vasopressin were significantly reduced in hepatocytes from CRF animals but
      PTX-CRF rats and those treated with verapamil had either significantly greater or
      even normal amounts of the mRNA of these receptors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8569096
TI  - Minimally invasive diagnosis of renal artery stenosis by spiral computed
      tomography angiography.
AB  - We prospectively compared in a blinded fashion spiral computed tomography
      angiography (CTA) with arteriography in 62 consecutive patients with suspected
      renal artery stenosis (RAS). For CTA 150 ml of contrast material were injected
      intravenously. Arteriography was performed by DSA technique with selective
      catheterization of renal arteries. Of the 157 visualized renal arteries 155 could
      be evaluated with DSA and a total of 157 with CTA. Sensitivity of CTA for RAS >
      or = 50% was 98% and the specificity was 94%. Comparison of the grade of stenosis
      as evaluated by DSA versus CTA showed: identical gradation in 59 arteries (DSA >
      or = 50%/CTA > or = 50%), underestimation by CTA in one artery (DSA 50 to 75%/CTA
      < 50%), and overestimation by CTA in six arteries (DSA < 50%/CTA 50 to 75%).
      Factors that may contribute to these differences include impaired renal function
      and possibly "underestimation" of ostial RAS by arteriography. One artery not
      evaluable by arteriography showed a 70% stenosis by CTA. CTA showed no major side
      effects. We conclude that CTA has the same accuracy for the diagnosis of RAS > or
      = 50% as arteriography. However, CTA is only minimally invasive, safe, and causes
      less discomfort to patients.

PMID- 8569097
TI  - A comparison between the use of recombinant hirudin and heparin during
      hemodialysis.
AB  - The purpose of this study was to determine the anticoagulant and antithrombotic
      potential of hirudin during hemodialysis by comparing the efficacy of dialysis
      with heparin to that of dialysis with recombinant hirudin (r-hirudin). Eleven
      patients with chronic renal failure and on maintenance hemodialysis were included
      in this open cross-over study. Conventional doses of heparin were administered
      during the first dialysis of the study. Two days later r-hirudin, at a dose of
      0.15 mg/kg, was given as a bolus at the start of the second dialysis. The mean
      decreases in plasma levels of urea, uric acid and creatinine were approximately
      50% after dialysis with both anticoagulants. Dialysis was therefore equally
      effective. However, effective dialysis with r-hirudin was achieved with a shorter
      activated partial thromboplastin time (APTT; range 65 to 103 seconds) compared to
      that with heparin (> 120 seconds), thereby decreasing the risk of bleeding.
      Markedly less 111In-labeled platelets accumulated at the inlet of the artificial
      kidney when r-hirudin was used, suggesting a smaller loss of hollow fiber volume.
      The results indicate that hirudin may be a suitable alternative anticoagulant for
      use during hemodialysis and it thus warrants further investigation.

PMID- 8569098
TI  - Thromboxane synthase expression co-localizes with infiltrating macrophages in
      renal allograft biopsies.

PMID- 8569099
TI  - Acute myeloma kidney.

PMID- 8569100
TI  - Structural motifs underlying voltage-dependent K+ channel function.

PMID- 8569101
TI  - Visualizing life on biomembranes by atomic force microscopy.
AB  - Since its invention in 1986, the atomic force microscope (AFM) has become one of
      the most widely used near-field microscopes. Surfaces of hard samples are imaged
      routinely with atomic resolution. Soft biological samples, however, are still
      challenging. In this brief review, the AFM technique is introduced to the
      experimental biologist. We discuss recent data on imaging molecular structures of
      biomembranes, and give detailed information on the application of the AFM with
      two representative examples. One is imaging plasma membrane turnover of
      transformed renal epithelial cells during migration in vivo, and the other is
      visualizing macromolecular pore complexes of the nuclear envelope of aldosterone
      sensitive kidney cells.

PMID- 8569102
TI  - Structure and function of the porin channel.

PMID- 8569104
TI  - Expression cloning of the epithelial sodium channel.

PMID- 8569103
TI  - Renal sodium channels: regulation and single channel properties.

PMID- 8569105
TI  - Defining topological similarities among ion transport proteins with anti
      amiloride antibodies.
AB  - The structural features of amiloride binding sites on amiloride-sensitive
      transport proteins have received limited characterization. An antibody that
      recognizes limited regions of amiloride and can mimic, in binding specificity,
      certain amiloride-sensitive transport proteins was used as a model to elucidate
      potential amino acid residue relationships that might define putative amiloride
      contact sites. Analysis of the structure of this antibody has allowed us to
      identify sequence relationships among several Na+ selective transport proteins. A
      structure-based relational database was employed to re-examine sequence
      homologies among these ion transport proteins. A search of the protein sequence
      databank identified representative amino acid tracts among amiloride sensitive
      proteins involving planar residues that might be involved in interacting with
      amiloride. Computer models of sites within transmembrane domains of NHE1 and NHE2
      isoforms of the Na+/H+ exchanger reflective of these planar tracts indicate that
      amiloride probably spans two helices for interaction with the Na+/H+ exchanger.
      Structural analysis of this monoclonal anti-amiloride antibody appears to mimic
      some of the salient features of amiloride binding sites on these proteins.

PMID- 8569106
TI  - Guanine nucleotide-dependent carboxymethylation: a pathway for aldosterone
      modulation of apical Na+ permeability in epithelia.

PMID- 8569107
TI  - Role of the actin cytoskeleton on epithelial Na+ channel regulation.
AB  - The regulatory role of actin filament organization on epithelial Na+ channel
      activity is reviewed in this report. The actin cytoskeleton, consisting of actin
      filaments and associated actin-binding proteins, is essential to various cellular
      events including the maintenance of cell shape, the onset of cell motility, and
      the distribution and stability of integral membrane proteins. Functional
      interactions between the actin cytoskeleton and specific membrane transport
      proteins are, however, not as well understood. Recent studies from our laboratory
      have determined that dynamic changes in the actin cytoskeletal organization may
      represent a novel signaling mechanism in the regulation of ion transport in
      epithelia. This report summarizes work conducted in our laboratory leading to an
      understanding of the molecular steps associated with the regulatory role of the
      actin-based cytoskeleton on epithelial Na+ channel function. The basis of this
      interaction lies on the regulation by actin-binding proteins and adjacent
      structures, of actin filament organization which in turn, modulates ion channel
      activity. The scope of this interaction may extend to such relevant cellular
      events as the vasopressin response in the kidney.

PMID- 8569108
TI  - Development of chloride channel modulators.
AB  - Chloride channels are ubiquitously distributed, biophysically varied and
      functionally diverse. Despite the known contribution of chloride channels to the
      physiology of various cell types and the pathology of several diseases, high
      affinity ligands are not available to study these channels. Here we report the
      iterative and integrated use of ion channel kinetic analysis and computational
      chemical methods in the development of high affinity blockers of the outwardly
      rectifying chloride channel (ORCC). Kinetic analysis, with emphasis on estimation
      of the block time constant as determined from critical closed time plots, was
      used to guide the synthesis of new disulfonic stilbene derivatives. Computational
      chemical methods were used to deduce the important features of the disulfonic
      stilbene molecule necessary for potent blockade of ORCC and ultimately led to the
      discovery of the calixarenes. Para-sulfonated calixarenes were found to be potent
      blockers of ORCC with subnanomolar inhibition constants and exceptionally long
      block times.

PMID- 8569109
TI  - Swelling-activated organic osmolyte efflux: a new role for anion channels.

PMID- 8569110
TI  - [Comparative value of Doppler graphic indices of blood flow rate and pressure in
      the assessment of the degree of lower limb ischemia].
AB  - The authors studied the dependence of Doppler graphic indices of blood flow and
      pressure at rest on the degree of ischemia of the lower limbs determined by the
      multistep treadmill test. They examined 50 patients with angiographically
      detected occluding lesions of the lower-limb arteries. The indices of pressure
      reflected the degree of the severity of lower-limb ischemia well, but the indices
      of linear blood flow rate did not correlate with it.

PMID- 8569111
TI  - [Topographic-anatomical bases of the use of the inferior epigastric artery in
      creation of free graft for aortocoronary shunt].
AB  - Ten experiments were conducted on nonfixed human cadavers of males and females 50
      to 70 years of age. The inferior epigastric artery arises from the medial wall of
      the external iliac artery 1.0-1.5 cm proximal to the inguinal ligament. Its
      diameter at the site of its origin varies from 2.5 to 4.0 mm and is 3.25 +/- 0.13
      mm on the average. At the level of the umbilical ring the average diameter of the
      artery is 1.47 +/- 0.03 mm. The total length of the arterial segment which can be
      used for transplantation varies from 11 to 16.5 cm, being 14.60 +/- 0.48 cm on
      the average. An approach through an inferomedian incision of the abdominal wall
      is preferable. The transplant is taken out together with the veins and the
      surrounding connective tissue. The length and diameter of the inferior epigastric
      artery are sufficient for using it as an aortocoronary shunt in revascularization
      of the myocardium in patients with ischemic heart disease.

PMID- 8569112
TI  - [Current possibilities of detection of thyroid cancer].
AB  - The article deals with 83 cases of carcinoma of the thyroid gland (CTG) which
      were recognized in 1973-1991 among the population during annual screening. The
      morbidity rate was 0.18 per 1,000 population, and increased by 3.4 times.
      Guidelines for Active Detection of Nodular Masses and Malignant Tumors of the
      Thyroid were elaborated. Their essence is as follows: during regular medical
      screening a group of individuals is distinguished in whom palpable abnormalities
      are found in the thyroid and focal changes are revealed in it by ultrasonic
      examination whose performance is recommended once every two years; the revealed
      group of individuals is subjected to complex examination for establishing the
      diagnosis, after which the tactics of their management are determined; a oncorisk
      group is formed to be kept under active observation. After introduction of the
      Guidelines into practice, recognition of CTG in stages I-II increased from 67.8
      to 80%, which testifies to their effectiveness.

PMID- 8569113
TI  - [Surgical treatment of diseases of operated stomach].
AB  - Surgical treatment of 293 patients with diseases of an operated on stomach is
      analysed. Relapse of peptic ulcer after closure of a perforation was encountered
      in 170 patients, the dumping syndrome in 54, peptic ulcer of the anastomosis in
      60, the afferent loop syndrome in 6, and a rare type of diseases of an operated
      on stomach in 3 patients. Classification of diseases of an operated on stomach
      according to the syndromes and differential diagnosis of functional syndromes are
      presented. Indications for surgical correction depending on the type and severity
      of the pathological condition were developed. The late-term results were studied
      in 266 patients. The results were good in 72%, satisfactory in 21%, and poor in
      7% of cases. The late-term results in surgical correction of functional syndromes
      were good in 29%, satisfactory in 51.6%, and poor in 13.5% of patients. Mortality
      after all repeated operation was 1.3%.

PMID- 8569114
TI  - [Significance of esophagojejunogastroplasty in the surgical treatment of chronic
      and malignant ulcers of the cardial part of the stomach].
AB  - A new method of esophagojejunogastroplasty with a continuous loop of the small
      intestine in proximal resection of the stomach was developed experimentally and
      introduced into clinical practice. The techniques of the operation are described
      in detail. Proximal subtotal resection of the stomach with
      esophagojejunogastroplasty was performed in 14 patients for chronic and malignant
      ulcers of the gastric cardia. Foci of adenocarcinoma were found in the edges of
      the ulcer in one patient and epithelial changes corresponding to CaC2 in situ in
      3 patients. One patient died after the operation from pulmonary artery
      thromboembolism. The course of the early postoperative period in the remaining 13
      patients was uneventful. Follow-up in postoperative periods of 4 weeks to 12
      months did not reveal any postresection disorders. All patients were capable of
      working and did not observe a special diet.

PMID- 8569115
TI  - [Effects of Helicobacter pylori on the results of conservative surgery in
      duodenal ulcer].
AB  - Sixty-two patients with exacerbation of duodenal ulcer were tested for
      Helicobacter pylori (HP). Bacterial invasion was found in 54 out 62 patients
      (87%). The degree of bacterial dissemination, the physiological resistance of the
      tegmental epithelium, and granulocytic infiltration of the mucosa were studied
      one and three months after selective proximal vagotomy (SPV) in 16 patients with
      HP. The control group consisted of seven patients without HP. It was found that
      bacterial invasion led to diminution of the physiological resistance of the
      tegmental epithelium and caused a chronic inflammatory process in the mucosal
      stroma. Bacterial dissemination after the operation not only corresponded to its
      initial level in the duodenum but tended to increase in the antrum and fundus of
      the stomach.

PMID- 8569116
TI  - [Comparative assessment of methods of extracorporeal detoxication in obstructive
      jaundice].
AB  - Comparative analysis of the methods of extracorporeal detoxification in 168
      patients was conducted. Endoscopic and surgical methods of treatment were applied
      in 40 patients without extracorporeal detoxification. Various types of
      extracorporeal detoxification were used along with endoscopic and operative
      methods in 168 patients: plasmapheresis (PP) in 72, thoracic duct (TD) drainage
      in 45, and hemosorption in 41 patients. In another 10 patients various types of
      detoxification were combined. TD drainage is indicated in prolonged obstructive
      jaundice, particularly when attended with cholangitis. TD drainage or PP is
      advisable in concomitant renal failure, PP and hemosorption have a good effect in
      obstructive jaundice as methods of emergency detoxification. Their efficacy
      increases if they are applied after endoscopic detoxification of the biliary
      tract.

PMID- 8569117
TI  - [Deep electrothermal burns].
AB  - Five-year experience in the treatment of patients with severe electrotrauma are
      analysed. They accounted for 3.1% of the total number of patients with burns. The
      treatment of such patients in of a long duration and expensive. This trauma
      nonetheless leads to irreversible affection of the organism and disability. The
      main success is determined by early surgical treatment before the development of
      pyo-inflammatory processes in the injured tissues.

PMID- 8569118
TI  - [Surgery of abdominal aorta occlusion].
AB  - The paper presents the authors' experience in surgically treating aortic
      occlusions in 325 patients. A total of 275 reparative operations were made from
      1978 to 1991. The authors proposed their own classification of aortic occlusions
      in terms of pathomorphological changes in the aorta and hence offered types of
      reparative operations and choice of surgical access. In extensive arterial
      lesions in the femoropopliteal area in combination with high aortic occlusion,
      the authors recommend that "two-story" reconstructions should be performed by
      including the distal arterial bed into blood flow. The intraoperative mortality
      was 1.4%.

PMID- 8569119
TI  - [Restoration of shape, position and skin of burn-damaged breasts].
AB  - Experience in the treatment of 24 females with restoration of 29 breasts which
      had been damaged by burns is discussed. In 16 of them the breast lay flat under
      scars. An effective method for restoring the shape and position of the breast in
      suggested. It consists in radical excision of the scars covering the glandular
      tissue, application of multilayer subcapsular circular retention sutures for 3
      months, and restoration of the skin over the breast with a split-skin graft or
      healthy skin taken from an adjacent area and stretched with an extender. Good
      cosmetic results were obtained in all cases, stable restoration of the shape,
      position, and skin over the breasts distorted by scars was achieved.

PMID- 8569120
TI  - [New antiseptics and disinfectants in surgery. I].
AB  - The efficacy of disinfectants and sterilizers made by Schulcke and Mayer
      (Germany), such as lysetol AF, gigasept FF, and TPH 5225 was studied in the
      laboratory and clinical settings. Their high activity was revealed when the
      agents were used in the clinical settings: lysetol for disinfection and
      presterilization cleansing of tools and medical equipment, gigasept FF for
      disinfection and sterilization of fine tools, endoscopic instruments in
      particular, TPH 5225 for disinfection of the surfaces of environmental objects
      under clinical conditions.

PMID- 8569121
TI  - [Intraoperative and early postoperative complications of vagotomy].
AB  - Intraoperative complications occurred in 28 (2.8%) and early postoperative
      complications in 157 (15.7%) out of 1,000 operations for vagotomy in duodenal
      ulcer (109 truncal, 64 selective, 445 isolated SPV, and 372 SPV combined with
      draining operations). Postoperative lethality was 1.3%. Controllable types of
      complications were encountered in 2.6%, prognostic in 9.6%, and non-prognostic in
      5.7% of cases. The first two groups of complications accounted for two thirds of
      the total number and determined the lethal outcome in 0.7% of the fatal cases.
      Thus, mastering of the operative techniques and realization of the complex of
      preventive measures allows the postoperative results of vagotomy to be
      considerably improved.

PMID- 8569122
TI  - [Complications after resection of the liver].
AB  - On the basis of experience in 228 radical resections of the liver (3.9%
      lethality) for focal affections, the authors analyze the causes of occurrence and
      measures of prevention of the main postoperative complications. The following
      factors play a role in the development of complications after liver resection:
      the patient's age, the character of the main and concomitant pathology, the
      volume of the operation and intraoperative blood loss, and the method of
      drainage. The prevention of postoperative complications is based on careful
      selection of patients for the operation, preoperative management, sparing
      operative techniques, adequate anesthesiological and trans-infusion service
      during the intervention, the use of cryoapparatuses and active management in the
      early postoperative period.

PMID- 8569123
TI  - [Surgical treatment of chronic disorders of duodenal transit].
AB  - New methods of surgical management of chronic duodenal patency impairments (CDPI)
      -desympathization of the gastroduodenal artery and a longitudinal-sectional
      cruciform duodenoenteric anastomosis supplemented by the longitudinal cover of
      the duodenum are described. The former is intended to create a vagal dominant in
      the nervous control of duodenal motility and indicated in functional diseases.
      The latter is designed for alimentary masses and digestive juices to move from
      the duodenum to the abducting part of the small bowel under force, which allows
      it to be used in all types of CDPI. Details of surgical techniques and procedures
      are substantiated on the basis of the author's clinical experience. An analysis
      of late postoperative outcomes used in the multimodality treatment of 80 patients
      with associated diseases has shown their high efficiency.

PMID- 8569124
TI  - [Prevention of wound infection in surgical treatment of alimentary-constitutional
      obesity].

PMID- 8569125
TI  - [Gunshot wounds of carotid arteries (on the 50th anniversary of the Victory)].

PMID- 8569126
TI  - [Prospects of early immunocytochemical diagnosis in periampullary tumors (a
      review of foreign literature)].

PMID- 8569127
TI  - [Gastric phlegmon].

PMID- 8569128
TI  - [Annular pancreas].

PMID- 8569129
TI  - [One-stage repair of the laryngopharynx and the cervical part of the esophagus
      with a free combined gastro-omental autograft using microsurgery technique].

PMID- 8569130
TI  - [Surgical treatment of injuries of the vertebral artery].
AB  - Surgical treatment of injury to the vertebral artery is one of the most difficult
      problems of modern vascular surgery. Six operations were carried out for injury
      to the vertebral artery at the Department of Vascular Surgery of the Tashkent
      Research Center of Surgery, Uzbekistan. In 3 patients the artery was ligated at
      the orifice. The performance of the compression test for excluding the
      possibility of the development of cerebral circulatory disorders is obligatory in
      all such cases. Two patients with injury to the vertebral artery in the medullary
      canal were treated by a method elaborated in the clinic and consisting in the
      tight filling of the canal with a mixture of warm wax and a collagen hemostatic
      sponge. In none of the cases were disorders of cerebral circulation and a
      clinical picture of vertebrobasilar insufficiency encountered. One patient died.

PMID- 8569131
TI  - The humoral immune response of children and infants to an RSV infection: its
      maturation and association with illness.
AB  - In this study the immune response of 29 newborns and infants hospitalized on
      behalf of a RSV infection was evaluated. Acute phase and convalescent sera were
      examined by a neutralization assay, in an immunoblot, and in an ELISA based on 10
      synthetic peptides derived from RSV proteins. The last two tests allow to monitor
      the synthesis of RSV specific antibodies of the infant. Despite the presence of
      maternal antibodies the initial immune response seems to be random and favours
      linear epitopes of the protein backbone of viral proteins. The earliest
      protecting antibodies directed against glycosylated epitopes are acquired in the
      second half year of life. Antibodies generated during the primary immune response
      seem to predispose infected children to get ill.

PMID- 8569132
TI  - [Therapy-induced formation of ascites and pleural effusion during initial
      chemotherapy in a patient with non-Hodgkin's lymphoma. Ascites and pleural
      effusion during initial chemotherapy].
AB  - We report on a 16-year old boy with non-Hodgkin's lymphoma who acquired a therapy
      induced ascites and pleural effusion during initial chemotherapy. This life
      threatening condition could be controlled by intensive care measures including
      pleural tap and drainage. Chemotherapy could then be continued. The patient has
      been in continuous complete remission for 18 months.

PMID- 8569133
TI  - [Pain crises in patients with sickle cell diseases. Pathogenesis, clinical
      aspects, therapy].
AB  - About 70% of all patients with sickle cell disease suffer from pain crises. Pain
      crises are recurrent episodes of pain that range in severity from mild to severe,
      usually occur very abruptly and are often localized around joints. Pain crises
      are caused by vaso-occlusions in the vascular bed of the bone marrow, leading to
      necrosis, edema and increased pressure. For effective analgesia morphine or
      morphine analogues are often required. When treating a pain crisis the patient's
      complaints need to be taken seriously and analgesic therapy should be started
      promptly with analgesics in proportion to the severity of the patient's pain.
      With mild pain oral non-opioid analgesics are sufficient, in moderate pain they
      are given in combination with oral codeine. Severe pain requires IV morphine,
      also combined with a non-opioid analgesic. Intravenous morphine makes a thorough
      monitoring of ventilation and level of consciousness mandatory. Sickle cell
      patients do not become drug dependent if given morphine for adequate analgesia.
      While bone marrow transplantation has become an accepted treatment modality for
      sickle cell patients with severe pain crises, treatment with hydroxyurea to
      increase HbF levels and reduce incidence and severity of pain crises, however, is
      still experimental.

PMID- 8569134
TI  - [Erythropoietin as a biochemical parameter for fetal hypoxia].
AB  - The ability of parameters like umbilical arterial pH and Apgar-score to predict
      and/or to reflect fetal distress is limited. It is known that erythropoietin
      (EPO) increases due to hypoxic stimulation. Therefore we studied the levels of
      EPO in the cord blood of stressed neonates (n = 75). In addition, reference
      values for EPO were established in a group of healthy term infants (n = 54) (mean
      +/- SD: 20.02 +/- 6.4; median 17.8; range 8.7-40.3 (mU/ml]) and in premature
      infants (n = 77) according to gestational age (median/range: < 30 weeks 11.0, 5.5
      17.5; 30-32 weeks 18.1, 5.5-136; 33-34 weeks 17.7, 8.3-422.9; 35-37 weeks 17.3,
      5.5-272 [mU/ml]). EPO concentrations significantly increased in the stressed
      group: in acute stress (n = 27): mean 153.4, range 6.5-641.7 [mU/ml], p < 0.003;
      and in chronic stress (n = 48): mean 102.6, range 12.4-544 [mU/ml], p < 0.002.
      However, parameters like hemoglobin, hematocrit, umbilical arterial pH and Apgar
      score did not correlate with EPO values. A sensitivity of 59% and a specificity
      of 92% was calculated. We conclude that serum EPO concentrations are capable of
      detecting acute and chronic stress. In part EPO also allows to grade stress in
      pregnancies, which are complicated by diseases like preeclampsia.

PMID- 8569135
TI  - [Computer-assisted monitoring in the neonatal intensive care unit].
AB  - Computerized monitoring in a neonatal intensive care unit allows continuous
      registration and complete storage of vital parameters. The stored data can be
      used for detailed retrospective analysis of critically ill patients and the
      graphical presentation of the vital parameters may lead to an earlier recognition
      of clinical deterioration. This computer system which can be established in any
      intensive care unit demonstrates the improvement in neonatal intensive care
      monitoring at low financial costs.

PMID- 8569136
TI  - [Supplementation of premature infant nutrition with calcium and phosphor for
      improving mineral supply of premature and small-for-gestational age newborn
      infants].
AB  - A standard preterm formula was supplemented with calcium (Ca) and phosphorus (P)
      (F-CaP: Ca 87 mg/dl, P 43 mg/dl) and compared to the non-supplemented form (F: Ca
      62 mg/dl, P 36 mg/dl). VLBW and small-for-gestational-age infants (n = 79) were
      included in the study which was performed to look for adverse effects and to
      decide about a reasonable start and duration of supplementation. In preterm
      infants with a birth weight lower than 1500 g and a body weight of more than 2000
      g, the additional supplementation with Ca and P lead to a significant higher Ca-
      and P-retention without further load for the kidney. In addition, preterm infants
      with a body weight lower than 1500 g also had a better retention of Ca and P.
      Both, F-CaP and F lead to a high urinary excretion of phosphorus, a high renal
      net acid excretion and a relatively high activity of serum alkaline phosphatase.
      Anthropometric measurements did not reveal any evidence for an impaired caloric
      absorption due to an increased fecal fat excretion. Hypercalcemia or
      hyperphosphatermia was not seen. Hypercalciuria occurred in less than 5% of the
      samples studied. The results of this study indicate that a continuation of the
      supplementation with Ca and P is justified in VLBW infants with a body weight of
      more than 2000 g. There was no evidence for adverse effects of Ca and P
      supplementation in VLBW infants with a body weight lower than 1500 g, who might
      therefore also benefit from supplementation. Further studies are necessary to
      investigate unsatisfactory metabolic conditions of these children e.g. the high
      renal load.

PMID- 8569138
TI  - [Imported visceral leishmaniasis (kala azar) in a German infant].
AB  - We here report the case of a 1 4/12 year old girl with visceral leishmaniasis.
      Returning from a trip to Mallorca she presented with pancytopenia, splenomegaly
      and fever and was admitted to hospital with suspected malignancy. Diagnosis was
      established microscopically from bone marrow smear and confirmed by PCR-assisted
      amplification of leishmania-specific DNA from peripheral blood. Treatment was
      conducted with stibogluconate for 25 days. Defervescence and improvement of
      clinical symptoms was seen after 4 days of treatment. Infection due to Leishmania
      donovani can be acquired throughout the entire mediterranean area and should
      therefore be included in the differential diagnosis of suspected malignancies in
      patients with a history of travel to mediterranean countries. PCR proved to be a
      sensitive tool for establishing the diagnosis of visceral leishmaniasis.

PMID- 8569137
TI  - [Analgosedation with fentanyl/midazolam after correction of congenital heart
      defects].
AB  - There is no standard therapy in the management of postoperative pain control
      following corrective cardiac surgery of congenital heart disease. Assessment in
      the preverbal age is difficult. In a randomized study we compared a combined
      treatment of fentanyl and midazolam, given as continuous infusion versus single
      dose application. A pain assessment score was used to measure the effectiveness
      of analgosedation in addition to recording nurseries observations. Fentanyl and
      midazolam are an appropriate combination for postoperative pain treatment.
      Continuous application is considered to be more effective concerning basic
      anxiety, cumulative dosage and to avoid volume overload in infants and young
      children, following cardiac surgery; overdosage was not observed.

PMID- 8569139
TI  - [Osteomyelitis of the ischium with ipsilateral hip dislocation in an infant].
AB  - Acute hematogenous osteomyelitis of the os ischii is a rare disease. Involvement
      of the acetabulum in a 4-month old girl with concomitant developmental dysplasia
      of the ipsilateral hip caused a dislocation of the hip joint due to synovitis.
      Arthroscopic joint lavage, antibiotic treatment and reduction of the hip in a
      pavlik-harness led to a satisfactory result.

PMID- 8569140
TI  - [Robin-Silverman-Smith (fetal face) syndrome].
AB  - Report of a case of the fetal face syndrome associated with severe oligophrenia
      and septum pellucidum cyste in a male patient aged 30 years. The case
      demonstrates the good prognosis of the hypogenitalism resp. small genitalia; the
      correct diagnosis in this syndrome can the patients save a plastic of the penis.

PMID- 8569141
TI  - [Kirner deformity].
AB  - A 14 years old boy with Kirner's deformity is demonstrated. He has the typical
      radial and volar deviation of the terminal phalanges of the 5th finger. Nature
      and inheritance of the disease are discussed. We assume inborn ossification
      disturbances. Most authors recommend to avoid any therapy. But we feel that
      nowadays it is possible to use plaster splints in young children or to do a
      corrective operation in older ones with good success.

PMID- 8569142
TI  - [Recommendations of the DGPI and PEG for antibiotic treatment of meningitis in
      newborn infants].

PMID- 8569143
TI  - Evaluation of tuberculin testing and measles prophylaxis procedures used in
      rhesus macaque quarantine conditioning protocols.

PMID- 8569144
TI  - Role of atrial natriuretic peptide in disturbed water and electrolyte metabolism
      of guinea pigs infected with Pichinde virus.
AB  - Daily intake and output of water and electrolytes (Na+, K+, and Cl-) were
      determined for 14 days in control and Pichinde virus-infected strain-13 guinea
      pigs. Although water intake began to decrease 7 days after virus inoculation,
      total daily water output (insensible water loss, urine excretion, plus fecal
      water loss) had little change. However, insensible water loss alone increased
      markedly in the virus-infected animals. Both intake and excretions of urinary and
      fecal electrolytes decreased at the middle (days 7 to 10) and late (days 11 to
      14) stages of viral infection. Differences between intake and output of water and
      electrolytes were reduced significantly during these periods. To determine a
      possible relationship between atrial natriuretic peptide (ANP) and urinary Na+
      and water excretion over intake, we measured plasma ANP concentrations. The mean
      control value of plasma ANP was 24 +/- 1.0 pg/ml, and plasma ANP concentrations
      of infected animals increased significantly (P < 0.01) to 49.5 +/- 3.9 and 51.3
      +/- 8.8 pg/ml on postinoculation days 7 and 12. Because the overall physiologic
      responses to Pichinde virus infection are complicated, it is difficult to
      postulate a single central theme concerning the pathogenesis. Nevertheless, we
      hypothesize that the virus-induced invisible tissue "biochemical lesions" and the
      consequential release of mediators and hormones were possible causes of death.
      Among other pathophysiologic mechanisms, the increased plasma ANP concentration
      may have played a role in the development of disturbed water and electrolytes
      metabolism during Pichinde virus infection.

PMID- 8569145
TI  - Enzyme-linked immunosorbent assay for detection of antibody to lymphocytic
      choriomeningitis virus in mouse sera, with recombinant nucleoprotein as antigen.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of
      antibody to lymphocytic choriomeningitis virus (LCMV) in mouse sera. This assay
      is based on recombinant LCMV nucleoprotein generated in a baculovirus system.
      Sera from experimentally and naturally infected as well as noninfected mice were
      tested, and the results were compared with those obtained from an established
      immunofluorescence assay (IFA) that uses infected cells as antigen. An excellent
      correlation was found; the ELISA specificity and sensitivity were calculated to
      be 100 and 95% respectively. Unlike the IFA, this ELISA does not require the
      handling of infective virus. It eliminates the need to work with a zoonotic agent
      in the laboratory while allowing effective screening of laboratory mouse
      populations for LCMV antibody.

PMID- 8569146
TI  - Hemangiomas and hemangiosarcomas in inbred laboratory mice.
AB  - Hemangiomas and hemangiosarcomas are rare, naturally developing tumors of blood
      vessels. In a retrospective study covering a period of 57 contiguous months
      between 1986 and 1991, four cavernous hemangiomas, eight capillary hemangiomas,
      and three hemangiosarcomas developed spontaneously in A/J, BALB/cJ, BALB/cByJ,
      C57BL/6J, NU/J, and 129/SvJ inbred mouse strains. When data were correlated to
      actual numbers of each sex in the colony, no sexual dimorphism was determined. At
      the time of submission, mice ranged in age from 100 to 434 days, with a mean of
      217 days. Tumors principally affected the skin but were also diagnosed in the
      seminal vesicles, liver, muscle tissue, and cerebellum. Immunohistochemistry,
      with antisera directed against human von Willebrand factor (factor VIII-related
      antigen) as an endothelial cell marker, labeled mouse endothelial cells
      inconsistently. A monoclonal antibody directed against the smooth muscle actin
      isoform, but not the sarcomeric muscle actin isoform, outlined vascular
      structures in tumors and normal vascular smooth muscle in adjacent normal
      tissues.

PMID- 8569147
TI  - Prevention and treatment of cilia-associated respiratory bacillus in mice by use
      of antibiotics.
AB  - The effects of continuous oral administration of antibiotics in mice were
      investigated. Sulfamerazine, ampicillin, and chlortetracycline were tested at a
      rate of 500 mg/L of drinking water. Mice were infected by intranasal inoculation
      with 10(6) bacilli of the SMR strain of cilia-associated respiratory (CAR)
      bacillus. The mice were treated with the antibiotics starting 1 week before, 1
      week after, or 4 weeks after the inoculation, for 5, 3, or 4 weeks respectively,
      then were examined. The infected mice lost body weight, and this loss was
      prevented or regained by all of the antibiotic treatments. Serologically no
      antibodies were detectable in the mice administered sulfamerazine starting 1 week
      before the inoculation. Mice administered sulfamerazine starting 1 week after the
      inoculation and ampicillin or chlortetracycline starting 1 week before or after
      the inoculation yielded a low titer of antibodies compared with nontreated
      infected mice. Mice administered antibiotics starting 4 weeks after the
      inoculation yielded the same titer of antibodies as nontreated infected mice. No
      pathologic respiratory tract lesions were observed in mice administered
      sulfamerazine starting 1 week before the inoculation. Mice administered
      sulfamerazine starting 1 week after the inoculation or ampicillin starting 1 week
      before or after the inoculation had slight peribronchitis without CAR bacillus
      colonization. Mice administered chlortetracycline, starting either 1 week before
      or after inoculation, developed peribronchitis, with colonization of the bacillus
      on the airway mucosa. In mice medicated starting 4 weeks after the inoculation,
      respiratory tract lesions developed, but their severity was reduced. The airway
      mucosa in mice treated with chlortetracycline was associated with the CAR
      bacillus but not in mice treated with sulfamerazine and ampicillin. These
      findings suggest that prevention and eradication of CAR bacillus infection is
      possible by treatment with sulfamerazine.

PMID- 8569148
TI  - Glaucoma in food-restricted and ad libitum-fed DBA/2NNia mice.
AB  - We allocated 110 DBA/2NNia mice of either sex to one of two feeding regimens: ad
      libitum (AL) or food restriction (FR) to 60% of the amount consumed by the AL
      group. The mice were examined at 3, 6, 9, 12, 18, and 24 months (at 3 months,
      only AL mice were examined). During the remaining periods approximately equal
      numbers (n = 10) of mice of both sexes and diet groups were examined. Peripheral
      anterior synechia was the first glaucoma-associated lesion observed and was
      present in 8 of 10 AL female mice, 6 of 10 AL males, and 1 FR male at 6 months.
      At 9 months peripheral anterior synechia was present in all AL females and was
      accompanied by depletion of retinal ganglion cells and degeneration of the optic
      nerves and optic tracts. Ninety percent of the eyes in the AL males also had
      peripheral anterior synechia at 9 months, but ganglion cell depletion and optic
      nerve degeneration were not observed as frequently. Neovascular membranes in the
      iridocorneal angle, a component of peripheral anterior synechia, were first
      observed at 9 months in approximately 55% of the globes of the AL mice and 5% of
      the FR mice. This was a major difference in the microscopic features of synechia
      between the diet groups and resulted in increased severity of synechia in the AL
      mice compared with their FR cohorts. Degeneration of the optic nerves and tracts
      was characterized by atrophy, astrogliosis, increase in cellularity,
      fragmentation of axons, and loss of myelin. Glaucoma in the FR mice of both sexes
      was less severe than in their AL counterparts. The most severely affected were AL
      females, followed by FR females, AL males, and FR males. Food restriction reduced
      the incidence and severity of the ocular lesions in females at all periods. The
      primary benefit of FR in males occurred during the 6- and 9-month periods when
      the incidence and severity of the glaucoma-related lesions were reduced; in the
      succeeding months the major benefit was minimal reduction of the severity of the
      lesions.

PMID- 8569149
TI  - Epizootic of low-virulence hepatotropic murine hepatitis virus in a nude mice
      breeding colony in Taiwan.
AB  - A natural outbreak of mouse hepatitis virus infection developed in a breeding
      colony of nude mice in Taiwan. The outbreak was unique in that morbidity was high
      in both adult and suckling mice, but only sucklings died. In contrast, all
      suckling heterozygous (nu/+) mice survived, and no lesions were found in adult
      female heterozygous (nu/+) mice. Adult male nude mice had chronic, active,
      necrotizing hepatitis with syncytial giant cells, but no lesions were detected in
      other tissues. Immunohistochemistry with anti-A59 and anti-JHM serum revealed
      mouse hepatitis virus antigen in the liver of infected adult and suckling nude
      mice, although less intensively in the kidney of adult nude mice. Suckling BALB/c
      mice inoculated with filtrates of the liver of adult nude mice developed
      hepatitis similar to that in the naturally infected nude mice. Virus was isolated
      by inoculating cell-free liver filtrate from infected adult nude mice onto 3T3
      cells. Electron microscopy of purified virus revealed 100-nm-diameter enveloped
      particles with characteristic petal-shaped surface projections. We conclude that
      the outbreak was caused by a weakly virulent, highly hepatotropic murine
      hepatitis virus.

PMID- 8569150
TI  - Detection of Ebola-Reston (Filoviridae) virus antibody by dot-immunobinding
      assay.
AB  - Thirty human and nonhuman primate sera tested at the Centers for Disease Control
      by enzyme-linked immunosorbent assay (ELISA), immunofluorescent antibody assay
      (IFA), and Western blotting were retested at the Virus Reference Laboratory, Inc.
      by the dot-immunobinding assay (DIA). The Ebola-Reston strain of virus received
      from the Centers for Disease Control was prepared into a suitable DIA antigen as
      described for other antigens. All six Western blotting-positive sera were also
      positive by DIA, as were the five ELISA-positive sera. Testing by IFA, the
      original test of choice, indicated an additional four seropositives, all negative
      by the other test systems. Of 288 randomly selected macaque sera, 19 were also
      found to be Ebola-Reston virus-positive by DIA.

PMID- 8569151
TI  - Protective immunity to Pasteurella multocida heat-labile toxin by intranasal
      immunization in rabbits.
AB  - Heat-labile Pasteurella multocida toxin (PMT) is an important virulence factor of
      some isolates from rabbits. To determine whether protective immunity to PMT could
      be induced in rabbits by intranasal immunization with heat-inactivated PMT, we
      immunized groups of rabbits intranasally at days 0, 7, 14, and 21 with
      inactivated PMT, with or without cholera toxin, an adjuvant for the mucosal
      immune system. Significant increases in anti-PMT IgA in nasal lavage samples and
      anti-PMT serum IgG, as determined by enzyme-linked immunosorbent assay, developed
      within 2 weeks after initial immunization. Coadministration of cholera toxin with
      inactivated PMT enhanced anti-PMT activity in the samples. Rabbits similarly
      immunized on days 0, 7, and 14 were challenged with PMT, and tissues were graded
      histologically on a numeric scale of lesion severity. Immunization conferred
      partial protection against development of pneumonia, pleuritis, hepatic necrosis,
      and testicular atrophy in rabbits challenged 16 days after initial immunization.
      Thus, immunization with inactivated PMT stimulates a protective response to PMT
      challenge in rabbits that is enhanced by coadministration of cholera toxin.

PMID- 8569152
TI  - Intestinal trichomoniasis due to Tritrichomonas mobilensis in tree shrews (Tupaia
      belangeri).
AB  - Intestinal trichomoniasis was observed in 156 of 202 Tupaia belangeri (77.2%).
      The parasites were located principally in the cecum (75%) and were far less
      common in the proximal portion of the colon (19%) or terminal portion of the
      ileum (6%). Advanced trichomoniasis was associated with liquid cecal contents but
      not diarrhea. The trichomonads had a tendency to penetrate the mucosal epithelial
      layer, causing desquamation of entire crypts. They never penetrated the
      epithelial basement membrane and never triggered inflammatory responses. The
      trichomonads were characterized by three anterior flagella and one trailing
      flagellum that extended over the entire parasite body, connected to it by an
      undulating membrane. The capitulum of the straight axostyle formed a small but
      well defined pelta, and the stout costa had distinct banding. The parasites
      thereby matched the description of Tritrichomonas mobilensis.

PMID- 8569153
TI  - Short-time rabbit model of endotoxin-induced hypercoagulability.
AB  - We describe a short-time endotoxin-induced rabbit model of hypercoagulability for
      the study of the coagulation cascade and the therapeutic effects of coagulation
      inhibitors. Cardiorespiratory function was maintained in rabbits under general
      anesthesia and standardized mechanical ventilation (tidal volume, 6 ml/kg; 60
      breaths/min) via tracheostomy and low-dose inotropic support. Coagulation
      parameters such as prothrombin time, activated partial thromboplastin time,
      thrombin time, fibrinogen concentration, platelet count, fibrin monomers, D
      dimers, antithrombin III and factor XIII activities, thrombelastography, and
      platelet aggregometry were measured during a 4-h period after sequential double
      endotoxin administration (80 and 40 micrograms/kg of body weight, intravenously).
      Mean arterial pressure and arterial and central venous blood gas tensions were
      monitored. Global clotting, activation parameters of coagulation, and leukocyte
      count deteriorated significantly in the endotoxin-treated animals but was mainly
      unaltered in controls (P < 0.05). Tissue specimens of the lungs, liver, brain,
      and kidneys were examined. Endotoxin-induced, disseminated fibrin deposition was
      found in the lungs and liver (P < 0.01). We conclude that this short-time model
      of hypercoagulability in rabbits reliably induced disseminated intravascular
      coagulation. Tracheostomy and mechanical ventilation provided a reproducible
      model in which the differences between the controls and the endotoxin-treated
      animals were exclusively due to administration of endotoxin and not to unforeseen
      complications of the respiratory system. This model allows the study of
      therapeutic effects of coagulation inhibitors on endotoxin-induced changes.

PMID- 8569154
TI  - Familial dysmyelination in a Long Evans rat mutant.
AB  - Tremors were observed in 15 Long Evans rats beginning at 10 to 12 days of age.
      These were followed by progressively worsening ataxia, hind limb paresis,
      episodes of immobility, and seizures by 5 to 14 weeks. Gross lesions were not
      observed at necropsy in rats euthanized and perfused at 4 to 16 weeks of age.
      Neurohistologic examination revealed dysmyelination in the central nervous
      system. Astrogliosis in the white matter with marked increase of expression of
      the glial fibrillary acid protein marker was accompanied by diffuse microgliosis.
      Scattered glial cells, interpreted to be oligodendrocytes, contained minute
      periodic acid-Schiff-positive cytoplasmic granules. Large mineralized periodic
      acid-Schiff-positive and laminated structures were observed in the cerebellar
      white matter, midbrain, and thalamus of rats over 6 weeks old. Neuronal
      degeneration and loss was evident in the cortex, hippocampus, and midbrain. Large
      axonal spheroids were found in the ventral and lateral funiculi of the spinal
      cord. An ultrastructural study of four affected rats revealed an almost complete
      absence of myelinated axons and normal sheaths, and degeneration and necrosis of
      oligodendrocytes. The Long Evans shaker rat represents a novel myelin mutant with
      a remarkable survival period and appears to have an autosomal recessive mode of
      inheritance.

PMID- 8569155
TI  - Quantification and lowering of serum biotin.
AB  - An enzyme-linked assay was developed to quantify serum biotin concentrations in
      experimental animals and humans. With this assay the effect on serum biotin
      concentration after intravenous injection of streptavidin or the addition of
      avidin to food was studied in rabbits and dogs. Intravenous injection of
      streptavidin reduced serum biotin values quickly but temporarily, in a dose
      dependent manner in both species. Addition of avidin to the diet lowered biotin
      values approximately four- to fivefold in the rabbits, with resultant biotin
      concentrations similar to those of humans.

PMID- 8569156
TI  - Normal hematologic values of various age groups of Calomys callosus (Rodentia
      Cricetidae).
AB  - Hematologic values for Calomys callosus, a wild rodent, were established. Males
      and females from a colony raised in Animal Housing of the Institute of Tropical
      Medicine of Sao Paulo were examined individually. For the red blood cell series,
      the number of erythrocytes, hemoglobin concentration, hematocrit, and platelet
      and reticulocyte numbers were measured. All values except hemoglobin
      concentration were slightly higher in aged animals than in young animals. The
      white blood cell series had a predominance of lymphocytes, with no age-associated
      changes.

PMID- 8569157
TI  - Morphologic study of the musculature of the third eyelid in the cat (Felis
      catus).
AB  - The presence of smooth and striated muscles associated with protrusion or
      retraction of the feline third eyelid was investigated histologically in eight
      cats. Nine smooth muscle strands extending into the third eyelid are described
      and illustrated. No striated muscle fibers extending into or within the third
      eyelid were observed.

PMID- 8569158
TI  - Effects of bilateral adrenalectomy on initiation of fur growth cycles in the deer
      mouse (Peromyscus maniculatus).
AB  - The objectives of this study were to determine the effects of bilateral
      adrenalectomy on the initiation of hair growth in the deer mouse and the duration
      of the actively growing phase of the hair growth cycle (anagen). Bilateral
      adrenalectomy plus deoxycorticosterone supplementation of adult deer mice
      resulted in the onset of hair growth 4 days earlier than in sham-operated mice
      supplemented with deoxycorticosterone. The duration of hair growth (anagen),
      based on guard hair measurements, was estimated to be approximately 12 days in
      both groups. As was expected for this species, the portion of the sheared test
      area in which new hair grew was incomplete in all control mice. In contrast, all
      adrenalectomized mice had hair growth over the entire sheared area. This suggests
      that normal, incomplete pelage replacement in adults was abolished and that
      adrenalectomy had a systemic effect, causing a greater number of hair follicles
      to become activated concurrently. These findings support the hypothesis that
      adrenal hormones exert an inhibitory effect on the induction of anagen and may be
      part of the mechanism controlling the onset of hair growth cycles.

PMID- 8569159
TI  - The anogenital distance index, a predictor of the intrauterine position effects
      on reproduction in female house mice.
AB  - The anogenital distances (AGD) of newborn female house mice vary as a function of
      prior intrauterine position. Females with long AGDs are more likely to be derived
      from intrauterine positions adjacent to males (2M) than females not adjacent to
      males (0M). Females with a male on one side (1M) show intermediate AGDs. Hence
      the AGD reflects the degree of androgenization experienced by the female in utero
      and correlates with a number of androgen-dependent anatomical, physiological, and
      behavioral events in adulthood. This experiment tested the usefulness of AGD
      measurements of female house mice taken at weaning rather than at birth as an
      index of prior androgenization. The AGD was normalized for body weight at weaning
      to yield an anogenital distance index (AGDI). Intrauterine position (IUP) was
      determined by caesarian section. Pups were marked and reared by foster mothers.
      Comparison of AGDI showed that 0M females had a significantly lower mean AGDI
      score than 2M females and 1M females were intermediate. This confirmed that AGDI
      reflects prior IUP and can be used as an index of prenatal androgenization. While
      testing for responsiveness to male urine, a stimulus known to accelerate puberty,
      only females from the 1M and 2M positions differed from controls indicating that
      0M females had already attained puberty. Choosing females from unknown IUPs with
      short-AGDIs, mid-AGDIs, and long AGDIs and treating them with either urine or
      saline on the nose for the 4 days after weaning yielded much the same response
      indicating that AGDI can also be used to preselect females for sensitivity to
      factors influencing puberty. These results demonstrate that some of the
      variability known to be related to intrauterine position can be predicted by
      AGDI, a relatively easy measure to acquire at weaning in commonly used laboratory
      rodents. Such preselection could reduce variability of experimental results in
      the conduct of studies related to rodent reproduction and may reduce the number
      of animals needed without loss of predictive ability.

PMID- 8569160
TI  - Hematologic values of the wild-caught karyotype V owl monkey (Aotus vociferans).
AB  - Blood samples from 35 wild-caught owl monkeys (Aotus vociferans, karyotype V)
      were analyzed to estimate reference intervals of hematologic variables for the
      species. Findings indicated that distributions were abnormal for leukocytes,
      neutrophils, eosinophils, basophils, and monocytes. Statistically significant sex
      differences, too small to be of clinical importance, were found in values for
      mean cell hemoglobin concentration, leukocytes, and basophils. Reference
      intervals for the hematologic variables were calculated by the nonparametric
      percentile estimation method. Comparison of hematologic reference values for wild
      caught A. vociferans with those of A. nancymae revealed statistically significant
      differences for packed cell volume, mean cell volume, leukocytes, eosinophils,
      basophils, and platelets. These differences also appeared too small to be of
      clinical significance.

PMID- 8569161
TI  - Physiological response to experimentally induced anemia in rats: a comparative
      study.
AB  - To induce anemia experimentally in rats to provide a hematocrit of 30 to 35% and
      provide data about the physiologic response to anemia during induction and after
      it is established, two methods were selected: the application of repetitive doses
      of phenylhydrazine and bleeding. Blood sample collection was carried out at
      various times, and hematologic profiles and osmotic resistance were evaluated.
      The morphologic features of cells and distinct organs also were examined. Results
      indicated similar decrease of hematocrit and hemoglobin concentration for the two
      experimental groups, although the reticulocyte response was higher in rats
      treated with phenylhydrazine, where the presence of young erythrocyte populations
      was linked to increases in osmotic resistance and glucose utilization. 2,3
      Diphosphoglycerate was induced only during the recovery phase of the study and
      corresponded to a gradual response to hypoxia. Histologically, marked erythroid
      hyperplasia was found in the bone marrow, and extramedullary hematopoiesis was
      seen in the spleen and liver.

PMID- 8569162
TI  - Effects of anesthesia with halothane and methoxyflurane on plasma corticosterone
      concentration in rats at rest and after exercise.
AB  - To determine whether halothane and methoxyflurane are suitable anesthetics for
      cardiac puncture in studies of plasma corticosterone concentration in rats, four
      experiments were done. Blood samples were taken immediately after rats became
      anesthetized with halothane or methoxyflurane. Decapitation without anesthesia
      was used to determine baseline corticosterone concentration. Another group of
      rats was anesthetized with ether as a positive control (known to stimulate
      corticosterone secretion). Corticosterone values in halothane- and methoxyflurane
      treated rats were not significantly different from those measured after
      decapitation. Corticosterone concentration in halothane-treated rats was
      significantly lower than that in either methoxyflurane- or ether-treated rats.
      Cardiac puncture was done after 3 min of exposure to each of the three
      anesthetics. The results indicated that there were no differences in
      corticosterone values among the three anesthetics, suggesting that corticosterone
      concentration was lower immediately after halothane was used as the anesthetic,
      because halothane induced anesthesia in less time than that required for
      activation of adrenocortical secretion. To determine whether there was a
      difference among anesthetics in stimulating corticosterone secretion when
      anesthesia was maintained for a period before blood sample collection, cardiac
      puncture was done after 15 min of exposure to each of the three anesthetics.
      Corticosterone values were similar, suggesting that any of the three anesthetics
      was acceptable in this situation. To determine whether halothane or
      methoxyflurane affected exercise-induced increases in corticosterone values,
      exercise-trained rats were run for 30 min; then blood samples were collected by
      cardiac puncture immediately after induction of anesthesia with halothane,
      methoxyflurane, or ether, or after decapitation without anesthesia.
      Corticosterone values were not different among the three anesthetics or
      decapitation.

PMID- 8569163
TI  - Technique for creating a permanent cecal fistula in the rat.
AB  - A method was developed to surgically implant a silicone/stainless steel fistula
      cannula in the cecum of freely moving rats. The specially designed fistula
      cannula allows sampling of cecal contents at any time without disturbing the
      physiologic functions of the intestinal tract, as evaluated by observation of
      general well-being and postmortem macroscopic inspection. The fistula-cannula was
      implanted in 12 male rats under general anesthesia. The animals remained in good
      health during the postoperative period lasting up to 9 weeks. They gained weight
      normally compared with a control group (n = 8) that had not undergone surgery.
      Samples of 0.2 to 1.0 g of contents could be collected with a microspatula,
      without the need to anesthetize the animal. The model provides a useful system
      for sampling cecal contents without the need to sacrifice the animal. Because it
      allows cross-over studies to be carried out, this approach may result in
      significantly reducing the number of animals required for digestive studies.

PMID- 8569164
TI  - Diagnostic exercise: anorexia, wasting, and death in South African clawed frogs.

PMID- 8569165
TI  - Diagnostic exercise: ophthalmitis in nude mice housed in ventilated Micro
      Isolator cages.

PMID- 8569166
TI  - Pathologic findings in an aging Mongolian gerbil (Meriones unguiculatus) colony.

PMID- 8569167
TI  - Evaluation of coculture aggregation with TT2 cells for production of germline
      chimera.

PMID- 8569168
TI  - Spontaneous vulvar carcinomas in 129/J mice.

PMID- 8569170
TI  - Evaluation of two commercial serologic tests for the diagnosis of Helicobacter
      pylori infection in the rhesus monkey.

PMID- 8569169
TI  - Expression of an ovine growth hormone transgene in mice causes organomegaly and
      hepatic lesions which resolve following transgene inactivation.

PMID- 8569171
TI  - Eisenmenger's syndrome in a New Zealand white rabbit.

PMID- 8569172
TI  - Clinically distinct subgroups of glioblastoma multiforme studied by comparative
      genomic hybridization.
AB  - Studies investigating genetic alterations potentially constituting prognostic
      factors in glioblastoma multiforme (GBM) have centered mainly around
      amplification events. Comparative genomic hybridization (CGH) is a recent
      molecular cytogenetic technique that allows the detection of chromosomal
      imbalances and amplification sites in tumor DNA prepared from fresh or archival
      material. A group of 94 patients with GBM underwent surgery followed by a
      standard course of radiotherapy. Neuroradiologic monitoring with gadolinium
      enhanced serial magnetic resonance imaging was applied to study the
      radiologically progression-free interval (RPFI) and tumor regrowth velocity.
      These parameters provided a clinical estimate of the postoperative tumor regrowth
      kinetics and yielded two clinically distinct groups. The most pronounced cases
      were selected from each group, i.e., those with the most favorable and
      unfavorable prognosis. Two subgroups with a statistically significant difference
      in RPFI (p < 0.001, Mann-Whitney U test) containing 10 patients each were formed:
      Subgroup A (slow tumor regrowth kinetics) and subgroup B (fast tumor regrowth
      kinetics). For a search of chromosomal alterations that might be correlated with
      tumor regrowth kinetics, we applied CGH to formalin-fixed, paraffin-embedded
      tumor tissue from these 20 patients. Except for autosomes 18 and 21, all
      chromosomes were involved at least once in copy-number aberrations. Events
      commonly associated with GBM, i.e., gains of chromosome 7, complete and partial
      losses of 9p, 10, and 22q, were not distributed differently between the two
      subgroups. The following differences were noticeable. Gains (including
      amplifications) of 12q14-q21 and of 19 were observed more often in subgroup A.
      Losses of 6q16-qter and parts of 13, and gains of 20, were more frequent in
      subgroup B. RPFI was significantly shorter for patients without amplification
      sites than for patients with gene amplification. RPFI did not differ
      significantly between patients with or without 7p12 amplification, where the
      epidermal growth factor receptor gene is localized. New amplification sites for
      GEM tumors were revealed at 11q13 and 11q22-q23. Loss of chromosome 10 was
      restricted to bands 10q25-q26 in one case. Although differences in the copy
      number karyotypes of patients with slow and fast postoperative tumor-regrowth
      kinetics were noted, the present CGH study did not reveal any single alteration
      useful as a prognostic factor. In particular, these data do not support the
      assumption that patients suffering from GBM with amplification events would have
      a poorer prognosis than others.

PMID- 8569173
TI  - Differential expression of elastin and alpha 1(I) collagen mRNA in mice with
      bleomycin-induced pulmonary fibrosis.
AB  - Interstitial pulmonary fibrosis is characterized by increased production of
      connective tissue components, including collagen and elastin. The role of elastin
      turnover in pulmonary fibrosis is not clear, and it is not known whether elastin
      and collagen are regulated separately or together during the inflammatory
      process. Mice with bleomycin-induced pulmonary fibrosis were investigated to
      determine the temporal and spatial changes in localization of elastin mRNA
      expression, as well as to compare elastin mRNA expression with that of alpha 1(I)
      collagen mRNA expression. In control (saline-treated) lungs, elastin mRNA was
      detected by in situ hybridization in arterial walls. No signal was found in
      alveolar or airway walls or in pleura; alpha 1(I) collagen mRNA was detected in
      the tissue underlying the airway epithelium. An increase in elastin mRNA
      expression in muscular arteries was observed 3 days after bleomycin instillation.
      Expression was also seen in the adventitia of terminal airways and adjacent small
      blood vessels. Expression of alpha 1(I) collagen mRNA increased in the tissue
      underlying the airway epithelium. In the pleura, alpha 1(I) collagen mRNA
      expression was found, although no pleural thickening was evident. The alpha 1(I)
      collagen mRNA expression was particularly increased in the adventitia of terminal
      airways and in associated small blood vessels. Obvious in areas of fibrosis,
      elastin mRNA expression was occasionally increased in the pleura and airway wall
      7 days after bleomycin treatment; alpha 1(I) collagen mRNA expression was
      generally stronger than elastin mRNA expression in areas of fibrosis and was
      frequently intense in the adventitia of airways and associated blood vessels. The
      fibrotic areas showed increased elastin mRNA expression 14 and 30 days after
      bleomycin treatment. The arteries in fibrotic areas showed normal elastin mRNA
      levels. In the areas of fibrosis and in the adventitia of airways and adjacent
      blood vessels, alpha 1(I) collagen mRNA expression was very high. In conclusion,
      lung elastin biosynthesis is markedly altered by bleomycin treatment. The
      localization and intensity of elastin mRNA expression is different from the
      expression of alpha 1(I) collagen mRNA.

PMID- 8569174
TI  - Diversity of the synthetic-state smooth-muscle cells proliferating in
      mechanically and hemodynamically injured rabbit arteries.
AB  - Vascular smooth muscles contain at least three types of developmentally regulated
      myosin heavy-chain (MHC) isoforms; SM1, SM2, and SMemb. By investigating the
      expression of the three MHC isoforms, we previously demonstrated in rabbits that
      smooth muscles proliferating in the neointima of arterio- and atherosclerotic
      lesions regain an "embryonic" phenotype. In the present study, we examined if
      neointimal cells are morphologically similar to embryonal smooth muscles and if
      dedifferentiation of neointimal smooth muscles is a reversible process. Vascular
      injury was produced in rabbits either by endothelial cell denudation of the aorta
      or by poststenotic dilation of the carotid artery. We have demonstrated in this
      study that the proliferating neointimal cells expressed SM1 and SMemb, but not
      SM2, indicating smooth muscles of an "embryonic" phenotype. The dedifferentiation
      of neointimal smooth muscles was found to be reversible; at 4 to 8 weeks after
      injury, a majority of the cells reexpressed both SM1 and SM2, but not SMemb. By
      electron microscopy, we have revealed smooth-muscle phenotypes determined by MHC
      isoforms to correspond to the morphologic phenotypes as an increase in membranous
      organelles, and a decrease in myofilaments was associated with the reexpression
      of SMemb. Interestingly, we also found that in the medial wall at 4 to 8 weeks
      after ballooning injury, a number of SM1-negative cells proliferated rapidly,
      replacing normal smooth muscles. These cells were negative against SM1 and SM2
      but positive for SMemb. These SM1-negative cells contained abundant membranous
      organelles and few myofilaments. These cells did not express SM1 or SM2 even
      after 8 weeks postinjury. We conclude from these results that the proliferating
      synthetic-type smooth muscles after vascular injury are composed of SM1-positive
      cells that are morphologically similar to embryonal smooth muscle and that
      maintain ability to redifferentiate, and SM1-negative cells that contain few
      myofilaments and remain dedifferentiated.

PMID- 8569175
TI  - Detection of allelic imbalance indicates that a proportion of mammary hyperplasia
      of usual type are clonal, neoplastic proliferations.
AB  - Previously, we developed methodology for studying allelic imbalance (AI) in
      preinvasive breast disease and showed that AI identified at various chromosomal
      loci in invasive carcinoma is already present in in situ carcinoma and atypical
      hyperplasia. We now extend this work by looking for Ai in hyperplasia of usual
      type (HUT), apocrine cysts (AC), and papilloma (Pap) of the breast. HUT, AC, and
      Pap were identified in formalin-fixed, paraffin-embedded sections of benign
      breast biopsies and isolated using a microdissection technique. AI was
      investigated using polymorphic microsatellite markers and PCR. AI was identified
      in 3/23 (13%) informative cases of HUT at 17q (D17S250), 2/43 (4.7%) at 17p
      (D17S796), 1/22 (4.5%) at 16q (D16S413), and 0/18 (0%) at 13q (D13S267). No
      particular histologic feature of HUT predicted the presence of AI. No examples of
      AC or Pap exhibited AI at any of the markers studied. AI previously identified at
      various chromosomal loci in invasive carcinoma, in situ carcinoma, and atypical
      hyperplasia is present at low frequency in HUT in benign breast biopsies but not
      in AC or Pap. The possibility that AI in the latter could be masked by
      contamination from stromal and myoepithelial cells cannot, however, be excluded
      at this stage. At least a proportion of HUT thus appear to be clonal (neoplastic)
      rather than hyperplastic proliferations as their name suggests. The significance
      of AI in the pathogenesis of HUT or its subsequent progression to carcinoma is
      not yet clear and requires further investigation.

PMID- 8569176
TI  - Measurement by quantitative reverse transcription-polymerase chain reaction of
      the levels of tumor necrosis factor alpha mRNA in atherosclerotic arteries in
      Watanabe heritable hyperlipidemic rabbits.
AB  - Tumor necrosis factor-alpha (TNF-alpha), produced by activated monocytes and
      other cells, has been proposed as a mediator of importance in atherosclerosis. In
      this study, we use a newly developed technique, quantitative reverse
      transcription-polymerase chain reaction (RT-PCR), to measure the mRNA levels of
      TNF-alpha in arteries of Watanabe Heritable Hyperlipidemic (WHHL) rabbits in
      relation to the progression of atherosclerosis. Co-amplification of known amounts
      of TNF-alpha RNA and TNF-alpha internal control RNA indicated that the
      quantitative RT-PCR method was quite reliable, with a < 5% difference between TNF
      alpha mRNA levels deduced from the standard curve and actually loaded TNF-alpha
      mRNA. As another control, TNF-alpha mRNA levels in lipopolysaccharide-induced
      (LPS-induced) and uninduced monocytes were measured, and a 9.3-fold increase in
      the TNF-alpha mRNA levels was observed in LPS-induced monocytes. TNF-alpha mRNA
      levels in the aortic arches of healthy New Zealand White (NZW) rabbits was 0.0112
      -/+ 0.0016 (SD) pg per ng tissue RNA. TNF-alpha mRNA levels in the aortic arches
      and descending thoracic aortas of 6-month-old WHHL rabbits were 0.0273 -/+ 0.0066
      pg and 0.0176 -/+ 0.0013 pg per ng tissue RNA, respectively. TNF-alpha mRNA
      levels in the aortic arches and descending thoracic aortas of 18-month-old WHHL
      rabbits were much higher than in those of 6-month-old WHHL rabbits, with values
      of 0.2107 -/+ 0.0205 pg and 0.1043 -/+ 0.0196 pg per ng tissue RNA, respectively.
      These findings indicate that: a) Quantitative RT-PCR can be used to measure
      levels of small abundance RNA in normal and diseased tissues accurately; b) no
      significant increase in TNF-alpha mRNA levels was observed in the aortic arches
      and descending thoracic aortas of 6-month-old WHHL rabbits compared with those of
      NZW rabbits, although they had multiple raised intimal lesions; and c) a
      significantly elevated total tissue level of TNF-alpha mRNA is demonstrable late
      in the course of atherosclerosis in 18-month-old WHHL rabbits (Bonferroni
      method). These findings suggest that TNF-alpha might play an important role in
      the progression of advanced atherosclerosis, although total tissue levels of TNF
      alpha mRNA are not unequivocally elevated earlier in the course of the disease.

PMID- 8569177
TI  - Role of neutrophils and lymphocytes in inhibition of a mouse mammary
      adenocarcinoma engineered to release IL-2, IL-4, IL-7, IL-10, IFN-alpha, IFN
      gamma, and TNF-alpha.
AB  - Impressive inhibition of tumor growth has been observed after transduction of
      cytokine genes into tumor cells. Secreted cytokines do not affect the
      proliferation of a tumor directly but activate a host immune reaction strong
      enough to overcome its oncogenic capacity. However, the reaction mechanisms
      activated are difficult to interpret; because these mechanisms have been derived
      from experiments with different tumors, comparisons are hindered. To compare the
      reactive mechanisms induced by each cytokine, BALB/c mice were challenged with
      the parental cells of the syngeneic spontaneous mammary adenocarcinoma TSA, or
      with TSA cells engineered to release IL2, IL4, IL7, IL10, IFN alpha, IFN gamma,
      and TNF alpha, and the tumor growth area was studied histologically,
      ultrastructurally, and immunohistochemically. These observations were integrated
      with data on the growth and rejection patterns of TSA cells in mice depleted of
      natural killer (NK) cells, granulocytes, CD4+, or CD8+ lymphocytes. The rejection
      of TSA-IL2 and TSA-TNF alpha cells was associated with the massive presence of
      neutrophils, that of TSA-IL4 and TSA-IL7 cells with neutrophils and very small
      areas of colliquative necrosis, and that of TSA-IFN alpha and TSA-IL10 cells with
      extensive areas of ischemic-coagulative necrosis and some neutrophils. TSA-IFN
      gamma cells displayed a delay in growth, but were not rejected. Their growth
      areas comprised necrotic zones of ischemic necrosis devoid of neutrophils. The
      selective depletion experiments demonstrated that rejection of engineered TSA
      cells depends on several leukocyte populations. The weight of each population
      varied with the secreted cytokine, although neutrophils and CD8+ lymphocytes
      constantly played the major role. Employment of the same tumor line engineered
      with the genes of different cytokines showed that each cytokine evokes a distinct
      reaction and that tumor inhibition results from a complex mechanism in which
      neutrophils and CD8+ lymphocytes and ischemic necrosis are of primary importance.

PMID- 8569178
TI  - Overexpression of nucleoside diphosphate/kinase A/nm23-H1 protein in human lung
      tumors: association with tumor progression in squamous carcinoma.
AB  - Levels of nm23-H1/nucleoside diphosphate/kinase A expression have been reported
      to correlate inversely with metastatic potential in some tumors but not in
      others. To clarify the role of nm23 in lung carcinoma, the genetic abnormalities
      of nucleoside diphosphate/kinase A/nm23-H1 were investigated at the DNA and
      protein levels. A series of 104 human lung tumors (42 neuroendocrine (NE) and 62
      non-NE tumors) was analyzed for nm23-H1 protein expression by
      immunohistochemistry using one polyclonal and two monoclonal Ab and for genomic
      alterations using Southern blotting and single-strand conformation polymorphism.
      Overexpression of the nm23-H1 protein relative to the normal lung epithelia
      (pneumocyte and bronchial epithelial cells) was observed in 83% (35/42) of NE
      carcinomas and in 89% (55/62) of non-NE carcinomas. Eight of nine carcinoids
      exhibited an increased expression of nm23-H1 protein, suggesting that this
      overexpression of the nm23 protein is necessary for proliferation in any tumors.
      No significant correlation was found between nm23 staining and any
      clinicopathologic parameters in NE carcinoma or in adenocarcinoma. In squamous
      carcinoma, high levels of nm23-H1 protein expression were associated with tumor
      stage (p = 0.0036). Allelic deletion or genetic amplification was never found. No
      altered mobility was detected using single-strand conformation polymorphism
      analysis. These data show that nm23-H1 protein is overexpressed in a large number
      of lung tumors of all histologic types, in association with advanced tumor stage
      in squamous carcinoma. They also suggest that nm23-H1 might play a role in the
      progression of lung tumors rather than in antimetastatic function.

PMID- 8569179
TI  - Messenger RNA for urokinase plasminogen activator is expressed in myofibroblasts
      adjacent to cancer cells in human breast cancer.
AB  - Urokinase plasminogen activator (uPA) is a serine proteinase involved in
      degradation of the extracellular matrix during cancer invasion. uPA is up
      regulated in breast cancer, and high levels of uPA in tumor extracts are strongly
      associated with poor prognosis. Like several other matrix proteinases, uPA is in
      some types of cancer, including breast cancer, expressed by stromal cells. The
      present study was undertaken to determine the identity of the uPA-expressing
      stromal cells in breast cancer tissue. By in situ hybridization, a positive
      signal for uPA mRNA was in 26 of 28 ductal and four of five lobular carcinomas
      demonstrated in stromal cells adjacent to nests of cancer cells, whereas only one
      ductal carcinoma showed a positive reaction in the epithelial component itself.
      The positive stromal cells were found in both the peripheral and central parts of
      the tumors. Stromal cells surrounding carcinoma in situ lesions were uPA mRNA
      positive in a few cases, and no signal was observed in the neighboring
      nonmalignant tissue. Cell identification was done by immunostaining with Ab to
      markers for the following cell types: myoepithelial cells, myofibroblasts, smooth
      muscle cells, macrophages, endothelial cells, and epithelial cells. The only one
      of these cell types that had a distribution similar to the uPA mRNA-expressing
      cells was myofibroblasts, recognized as extravascular alpha-smooth muscle actin
      positive and cytokeratin-negative cells. On adjacent sections, colocalization was
      found of cells positive for uPA mRNA and cells positive for alpha-smooth muscle
      actin and negative for cytokeratin. We concluded that the uPA mRNA-expressing
      cells are myofibroblasts. The myofibroblasts have previously been found to be
      abundant in breast cancer tissue. They primarily originate by differentiation of
      fibroblasts, probably induced by cytokines released from the cancer cells. The
      present findings suggest that the myofibroblasts, through production of uPA, play
      an active role in breast cancer invasion.

PMID- 8569180
TI  - Vasopressin-induced heat shock protein expression in renal tubular cells.
AB  - Heat shock proteins (HSPs), which have been shown to be induced in the kidney by
      a variety of stress conditions, including ischemia, inflammation, oxidative
      stress, and toxin exposure, are believed to protect the cells from injury. In the
      present study, we demonstrated that administration of vasopressin i.v. to Wistar
      rats leads to HSP70 induction in the kidney. The effect was specific to the
      kidney (i.e., absent in brain, heart, lung, muscle, etc.) and selective for the
      HSP70 gene family (HSP27, HSP60, and HSP90 were not induced). Western blot
      analysis demonstrated that HSP70 protein expression peaked between 6 and 12 hours
      after vasopressin administration. Immunohistochemical staining revealed that
      induction was localized to renal tubule lining cells, with no expression seen in
      glomerular or interstitial regions. The elevated protein levels were preceded by
      the induction of HSP70 mRNA within 30 minutes after vasopression injection. The
      induction of HSP70 mRNA was associated with the activation of heat shock
      transcription factor 1 (HSF1), suggesting that the response was regulated at the
      level of transcription. This HSP70 expression was completely blocked in the
      presence of both a general vasopressin receptor antagonist (V1 and V2 receptors)
      and an antidiuretic antagonist (V2), but not in the presence of a vasopressor
      antagonist (V1). These observations could be significant for understanding the
      possible involvement of HSP70 in physiological processes of the kidney, as well
      as pathophysiologic conditions associated with either elevated or deficient
      levels of vasopressin.

PMID- 8569181
TI  - Coexpression of platelet-derived growth factor alpha and beta receptors on
      medulloblastomas and other primitive neuroectodermal tumors is consistent with an
      immature stem cell and neuronal derivation.
AB  - Medulloblastomas and related childhood primitive neuroectodermal tumors (PNET)
      are currently thought to originate from a multipotent stem cell that can give
      rise to a variety of different tumor types, representing different lines of
      differentiation and stages of maturation of the original stem cell. The
      proliferation and differentiation of different cell types in the central nervous
      system are influenced by growth factors, such as platelet-derived growth factor
      (PDGF). In this study, we investigated the expression of the two types of PDGF
      receptors, alpha and beta, on 14 cases of PNET by immunohistochemistry and in
      situ hybridization. To characterize the tumor cells according to their
      differentiation and maturation, we performed immunohistochemistry with Ab against
      several members of the intermediate filament family, such as neurofilament, glial
      fibrillary acidic protein, vimentin, and the embryonal marker nestin. For the
      cerebral PNET, we found that the phenotype of multidirectional differentiation
      (with coexpression of neurofilament, glial fibrillary acidic protein, vimentin,
      and in some cases nestin) was associated with the expression of both PDGF alpha
      and beta receptors on the tumor cells. Medulloblastomas (i.e., cerebellar PNET),
      however, often showed the phenotype of partially committed neuron-like precursor
      cells, and this was associated with the predominant expression of PDGF alpha
      receptors on the tumor cells. Our findings show that the PDGF alpha receptor,
      previously known to play a role in the normal development of cells of the glial
      lineage, either exclusively or in combination with the PDGF beta receptor, is
      expressed on tumor cells of neuronal derivation. This "aberrant" expression of
      PDGF alpha receptors on PNET may reflect a feature of the malignant phenotype of
      these tumors. Further studies are needed to study the biologic effects of PDGF-A
      and its receptor in PNET.

PMID- 8569182
TI  - Formation of focal adhesion and spreading of polarized human colon cancer cells
      in association with tyrosine phosphorylation of paxillin in response to phorbol
      ester.
AB  - Regulation of cell adhesion systems is involved in both normal development and
      the invasive behavior of carcinomas. We examined alterations of cell morphology
      and adhesion molecules in response to phorbol ester treatment of the SW1116 colon
      cancer cell line, which forms well-organized dome-like tubular structures in
      culture. 12-O-Tetradecanoylphorbol-13-acetate (TPA) induced rapid spreading of
      cancer-cell colonies through formation of focal adhesion and disappearance of
      adherens junctions. Immunologic analyses demonstrated that tyrosine
      phosphorylated proteins were concentrated at focal adhesions, and that tyrosine
      phosphorylation of two proteins, paxillin and an unidentified 130-kd protein, was
      significantly increased. Tyrosine phosphorylation of paxillin was detectable
      within 15 min after TPA treatment, when only lamellipodia had extended from the
      colony, and in cells treated with blocking antibodies against integrins beta 1
      and beta 5, which strongly inhibited spreading and disorganization while
      preserving adherens junctions. The level of paxillin phosphorylation correlated
      well with the degree of morphologic change induced by low-dose TPA, and the
      dephosphorylation occurred before reversion of morphology upon removal of TPA.
      These findings suggest that the TPA signal was transduced to the tyrosine
      phosphorylation of paxillin strongly associated with formation of focal adhesion,
      and that this in turn induced dysfunction of the cadherin system and caused
      spreading and disorganization of the tubular structure. The mechanism responsible
      for disruption of the cadherin system at adherens junctions was not clear, but
      the transition of beta-catenin into nuclei corresponded to the disappearance of
      its signal along areas of cell-cell contact. This SW1116 model provides a good
      system for studying the molecules involved in transient regulation and crosstalk
      between the cell-cell and cell-substratum adhesion systems, which may explain the
      mechanism of invasion of well-differentiated human carcinomas.

PMID- 8569183
TI  - Increased immunoreactivity and protein tyrosine kinase activity of the
      protooncogene pp60c-src in preneoplastic lesions in rat pancreas.
AB  - This study investigates the possibility that the c-Src protein tyrosine kinase is
      involved in experimental exocrine pancreatic carcinogenesis. Expression and
      activity of the protooncogene pp60c-src (c-Src) are investigated in acinar
      pancreatic (pre-) neoplastic lesions induced in rats by azaserine and compared
      with normal rat pancreas. Low or absent c-Src immunoreactivity and c-Src tyrosine
      kinase activity were found in the pancreas of untreated control rats. Compared
      with these controls, c-Src protein immunoreactivity was increased in "normal"
      acinar cells and even more in putative preneoplastic atypical acinar cell nodules
      (AACN) after azaserine treatment. In contrast, more advanced (secondary
      transformed) acinar cell lesions demonstrated no c-Src immunoreactivity. Rats
      treated with azaserine showed a 7-fold-higher c-Src tyrosine kinase activity in
      their pancreas. The level of c-Src tyrosine kinase activity correlated positively
      with the number of lesions in the pancreas, inasmuch as promotion of azaserine
      initiated carcinogenesis by cerulein resulted in a more than 10-fold increase in
      the number of AACN, which was accompanied by a 6-fold increase in c-Src activity
      when compared with azaserine treatment alone. c-Src tyrosine kinase activity was
      responsible, on average, for 40% of the total tyrosine kinase activity in the
      pancreatic homogenates and was predominantly found in the cytoskeletal
      subcellular fraction. Furthermore, the transformation from normal to
      preneoplastic pancreatic tissue in azaserine-treated rats was accompanied by a
      change in the localization of the c-Src protein. With the use of
      immunohistochemistry and confocal laser scanning microscopy, the protein was
      detected in the cytoplasm in morphologically normal pancreatic acini, whereas in
      AACN it was detected both in the cytoplasm and in the nuclei. It is concluded
      that the protooncogene c-Src might be involved early in experimental pancreatic
      carcinogenesis: c-Src probably plays a minor role in pancreatic acinar cells
      after transformation to malignancy.

PMID- 8569184
TI  - Overexpression of surfactant protein SP-A, SP-B, and SP-C mRNA in rat lungs with
      lipopolysaccharide-induced injury.
AB  - Regeneration of alveolar epithelial cells is one of the important repair
      processes in many types of lung injury. We have examined sequential analysis of
      histopathology and gene expressions of surfactant protein A (SP-A), SP-B, and SP
      C mRNA in alveolar type II cells of rats with lipopolysaccharide-induced (LPS
      induced) lung injury. A small dose (1 to 2 mg/kg) of LPS was injected by
      intratracheal instillation in adult rats, and after a given period, the lungs
      were processed for examination using light and electron microscopy, for
      immunohistochemical study using anti-bromodeoxyuridine (anti-BrdU) and anti-SP-A
      antibodies, and for in situ hybridization using type-specific, surfactant cDNA
      probes. Northern blot analysis was also performed. From 3 to 7 days after LPS
      administration, alveolar septa were thickened, with increased numbers of
      epithelial and interstitial cells. BrdU-incorporated cells apparently increased
      in number in these areas, and many alveolar epithelial cells were intracellularly
      immunoreactive to anti-SP-A antibody, with many lamellar bodies found on
      examination using electron microscopy. By in situ hybridization, the number of
      autoradiographic silver grains for SP-A, SP-B, and SP-C mRNA increased
      strikingly, in alveolar type II epithelial cells of the lungs from LPS
      administered rats. These responses of surfactant gene expression to LPS seemed to
      be stronger in alveolar epithelial cells than in the bronchiolar epithelium. By
      Northern blot analysis, the relative abundances of SP-A, SP-B, and SP-C mRNA were
      also higher in the LPS-administered lungs and correlated well with the results of
      in situ hybridization. The present study demonstrates that intratracheal
      administration of LPS induces the marked proliferation of alveolar epithelial
      cells in association with the concurrently increased SP-A, SP-B, and SP-C mRNA,
      as well as the SP-A production in the early response to lung injury. These
      results suggest that proliferation and differentiation of alveolar epithelial
      cells may play important roles in the repair process of the damaged alveoli after
      acute lung injury.

PMID- 8569185
TI  - Laminins 2 and 4 are expressed by human decidual cells.
AB  - During pregnancy, the resident stromal cells of the endometrium differentiate to
      become decidual cells and produce a pericellular basement membrane. We used
      immunofluorescence and Western blotting with a panel of monoclonal Ab specific
      for various laminin subunits to examine the composition of decidual laminin. The
      stromal cell basement membrane contained subunits alpha 2 (M), beta 1 (B1), beta
      2 (S), and gamma 1 (B2). Low levels of alpha 1 could also be detected. The
      glandular and vascular basement membranes of decidual tissue contained subunits
      alpha 1 (A), beta 1, and gamma 1. An extract was produced from decidual
      extracellular matrix. Western blots of nonreducing gels showed the presence of
      high molecular weight complexes containing alpha 2, beta 1, beta 2, and gamma 1.
      These data indicated that laminins 2 and 4 are coexpressed by decidual cells.
      Laminin 1 was present in the extract as a minor component. In contrast, cultured
      stromal cells expressed laminin 1 as the major secreted variant.
      Immunolocalization was carried out using tissue from various stages of the
      nonpregnant cycle. The alpha 2 chain polypeptide was absent in the proliferative
      phase of the cycle but present in late secretory phase in perivascular areas
      where predecidual differentiation occurs. Reverse transcriptase-PCR experiments
      confirmed the presence of alpha 2 chain mRNA in decidua but showed that this
      transcript is detectable throughout the nonpregnant cycle. The results showed
      that laminins 2 and 4 are hormonally regulated products of decidual cells. The
      composition of the vascular and epithelial basement membranes remained constant
      throughout the cycle.

PMID- 8569186
TI  - Experimental reovirus serotype 1/strain Lang infection of the lung: a model for
      the study of the lung in the context of mucosal immunity.
AB  - A number of studies have examined the nature of the respiratory immune response
      to particular pathogens. Although many pathogens stimulate specific immunity in
      the lung, they frequently are not effective immunogens at other mucosal sites.
      Because the gastrointestinal tract is a major inductive site for mucosal
      immunity, a pathogen that is an effective respiratory and gut immunogen would
      allow studies of the interaction of the lung with gut mucosal immune system.
      Reovirus, a respiratory isolate that previously has been shown to be an effective
      gut mucosal immunogen, provides a potential model of the relationship of the lung
      to the gut mucosal immune system. In this report, we demonstrate that intranasal
      application of reovirus serotype 1/strain Lang (1/L) to CD-1 mice elicits an
      acute lymphocytic inflammatory infiltration of the lung and hyperplasia of the
      lung-associated lymph nodes. The initial inflammatory response occurs in the
      airspaces and interstitium of the lung. As the infection progresses, the
      initially diffuse cellular infiltrate becomes more focused around small
      bronchioles. Viral replication occurs predominantly during the first week of the
      infection, and infectious virions are eliminated during the second week. After
      the elimination of infectious virions, a secondary response consisting of the
      appearance of plasma cells adjacent to pulmonary arteries develops as the primary
      infiltrate organizes into peribronchiolar follicles, resembling the human
      inflammatory lung condition termed follicular bronchiolitis. These two
      infiltration patterns were also observed by immunohistochemical analysis of the
      the infected lung. Whereas CD4+ and CD8+ lymphocytes and Mac-1+ cells were found
      to be more closely associated with the primary infiltration process, B220+
      lymphocytes were observed adjacent to pulmonary arteries. These results establish
      respiratory reovirus 1/L infection as a viable model for future investigations of
      the mucosal immune response in the lung and its relationship to the common
      mucosal immune system.

PMID- 8569188
TI  - Coexpression of heat-shock protein 60 and intercellular-adhesion molecule-1 is
      related to increased adhesion of monocytes and T cells to aortic endothelium of
      rats in response to endotoxin.
AB  - Bacterial cell-wall lipopolysaccharide (LPS) is the main endotoxin contributing
      to local inflammation and systemic toxicity during Gram-negative infections and
      induces aortic endothelial injury with or without cell death and replication
      followed by increased leukocyte adhesion. Heat-shock protein (hsp) 60 is under
      study in our laboratory as a potential antigen inducing immunologic attack to
      endothelial cells in atherogenesis. To investigate the mechanism of LPS-induced
      endothelial injury and the phenotypes of adhering cells, Lewis rats were treated
      in vivo or, in aortic organ cultures, with LPS to determine the expression of
      intercellular-adhesion molecule-1 (ICAM-1) and hsp60 on aortic endothelium and to
      characterize phenotypes of adhering leukocytes. Increased ICAM-1 expression by
      aortic endothelium was observed as early as 3 hr after LPS injection and
      persisted up to 72 hr, whereas elevated levels of hsp60 were found between 6 and
      48 hr. In vitro application of various types of stress, such as LPS, H2O2, and
      high temperature, not only stimulated endothelial expression of hsp60 but,
      concomitantly, that of ICAM-1. The number of adhering leukocytes was
      significantly increased on aortic endothelium 6 hr after LPS administration, and
      the predominant leukocytes adhering to stressed endothelium were monocytes (80%)
      and T lymphocytes (8 to 20%). In organ cultures of rat aortic intimal, LPS, and
      H2O2 evoked increased leukocyte adhesion, which proved to be selective, because
      adherent leukocytes were mostly Ia+ monocytes and T cells, i.e., activated.
      Adhering T cells were gamma/delta antigen-receptor positive in 8 to 16% after LPS
      stress, whereas these cells amount to only 2 to 4% of peripheral blood T cells.
      Blocking of adhesion molecules ICAM-1, LFA-1 alpha, and/or LFA-1 beta reduced
      adhesion up to 34%. Increased coordinated LPS-dependent expression of hsp60 and
      ICAM-1 correlates with monocyte and T-cell adhesion to aortic endothelium. These
      observations may be significant for elucidating the mechanism of the initiating
      events in the development of atherosclerosis.

PMID- 8569187
TI  - Chondrocyte matrix metalloproteinase-8: up-regulation of neutrophil collagenase
      by interleukin-1 beta in human cartilage from knee and ankle joints.
AB  - The loss of aggrecan from articular cartilage may lead to the development of
      osteoarthritis (OA). Degradation products of human aggrecan, generated in vivo by
      enzymatic cleavages, have been identified in synovial fluid of patients with
      rheumatoid arthritis and OA. One matrix metalloproteinase (MMP), stromelysin (MMP
      3), and an unidentified proteinase called "aggrecanase" are believed to generate
      these products in pathologic conditions. Thus far, only one proteinase,
      neutrophil collagenase (MMP-8), has been shown in vitro to be capable of cleavage
      of the aggrecan molecule at the "aggrecanase" site. In this study, we compare the
      presence and distribution of MMP-3 and MMP-8 in cartilages from two different
      joints of normal human donors. We determined whether mRNA for MMP-8 is expressed
      in normal human articular cartilage from different joints. In addition, we
      compared differences in MMP-8 and MMP-3 gene expression between human ankle and
      knee cartilage after in vitro stimulation by interleukin (IL)-1 beta. These two
      joints were chosen because the incidence of symptomatic and radiographic OA
      varies between the different joints. The knee is the most frequently involved
      joint, whereas the ankle (talocrural) joint is relatively rarely affected.
      Message for MMP-8 was detected in untreated cartilage from normal knee joints,
      but not in untreated cartilage of normal ankle joints. Message for MMP-3 was
      detectable in most of the knee and ankle cartilages. Messenger RNA expression for
      both MMPs could be up-regulated by IL-1 beta. The highest doses of IL-1 beta
      appeared to be most effective in stimulation of mRNA for MMP-3, whereas MMP-8
      expression was more sensitive to lower doses of IL-1 beta. The fact that ankle
      cartilage with a low incidence of OA does not express MMP-8, whereas knee
      cartilage with a high incidence of OA does not express MMP-8, whereas knee
      cartilage with a high incidence of OA does constitutively express MMP-8, suggests
      that MMP-8 might be one of the key enzymes in the pathogenesis of osteoarthritis.
      This is further supported by our finding that the earliest signs of cartilage
      degradation were very similar to those found in IL-1 beta-treated explants.

PMID- 8569189
TI  - Increased placental antifibrinolytic potential and fibrin deposits in pregnancy
      induced hypertension and preeclampsia.
AB  - Preeclampsia is characterized by maternal hypercoagulable state and intravascular
      coagulation, microthromboses in several organs, and impairment of uteroplacental
      circulation. Excessive fibrin deposition occurs in the placenta, suggesting that
      disorders of placental coagulation and fibrinolysis physiologic systems may have
      a role in hemostasis activation. Term placentas were collected from 17
      hypertensive/preeclamptic women and from 17 healthy pregnant women, and processed
      for both histologic and hemostasis studies. Placental fibrinoid deposition was
      visualized by cresyl-violet staining and quantified by histomorphometric
      analysis. The content in hemostasis factors was measured on extracts from
      homogenized placentas treated by a nonionic detergent. The percentage of villi
      with fibrinoid deposits was higher in the diseased placentas than in controls:
      13.2 +/- 11.2 versus 6.75 +/- 2.7% (p < 0.001) for the total amount of deposits;
      4.8 +/- 6.7 versus 1.5 +/- 1.0% (p = 0.04) for perivillous fibrinoid deposits,
      which are considered as histologic markers of intraplacental fibrin. The content
      in type 2 plasminogen activator inhibitor (PAI-2) antigen was higher in the
      diseased placentas than in controls: 124 +/- 8 versus 104 +/- 6 ng/mg placental
      protein (p = 0.046); there was a negative correlation between PAI-2 antigen and
      thrombomodulin activity (r = -0.57, p = 0.02) in the diseased placentas. No
      significant differences were found between the two groups for placental
      procoagulant tissue factor and anticoagulant thrombomodulin activities, and for
      the content in plasminogen activators and PAI-1 antigens. Placental
      antifibrinolytic potential is increased in pregnancy-induced hypertension and
      preeclampsia. This change, and the association of the highest PAI-2 placental
      concentrations with the lowest concentrations of thrombomodulin, may contribute
      to the prethrombotic state and to the excessive placental perivillous fibrin
      deposition observed in these situations.

PMID- 8569190
TI  - Amyloid enhancing factor is produced by rats and amyloid-resistant CE/J mice.
AB  - Amyloid enhancing factor (AEF) is an operational term applied to poorly defined
      extracts of amyloidotic or preamyloidotic tissues capable of shortening the
      induction time of amyloid deposition in recipient mice from 1 to 2 weeks to 48 to
      72 hours. Its derivation has always left open the question of whether activity
      was dependent on the presence of amyloid fibrils or preamyloid fibril fragments.
      In these studies, we have assayed AEF activity in extracts of spleen and liver
      from azocasein-injected rats and CE/J mice that do not develop amyloidosis and,
      hence, cannot have amyloid A (AA) fibrils or fibril fragments in their tissues.
      Susceptibility to amyloid induction was compared in three strains of mice and
      three strains of rats by subjecting each group of experimental animals to
      multiple injections of azocasein. Spleens and livers were removed 24 hours after
      the last injection, and samples of all tissues were examined for amyloid
      deposits. AEF was extracted from the remainder of the tissues taken from amyloid
      resistant CE/J mice and Sprague-Dawley rats. Graded doses of the resulting tissue
      extract were given to naive Swiss-Webster (SW) recipient mice by i.p. injection
      concomitantly with subcutaneous injection of 0.5 ml 2% AgNO3. All tissues from
      both CE/J mice and rat donor animals were negative for amyloid by histologic
      examination of Congo Red stained samples, as were the AEF extracts. All recipient
      mice (six of six) given 600 micrograms of the CE/J-derived AEF developed large
      amyloid deposits in their spleens (mean severity 3.7 -/+ 0.3 SEM). Lower doses
      (200 micrograms protein) resulted in similar incidence of amyloid accumulation
      (in four of five), but quantitatively smaller amounts of amyloid protein were
      present. Doses of 100 micrograms decreased incidence (in one of five), whereas
      animals receiving 50 micrograms were all negative. AEF derived from rat tissues
      also induced high incidence of amyloid (in four of five) at high doses, although
      the amount of AA protein was less than in mice given equivalent amounts of CE/J
      mouse-derived AEF. Although 200 micrograms and 100 micrograms of rat AEF was
      effective (in two of five and one of five, respectively), 50 micrograms did not
      result in demonstrable amyloid deposition. The presence of AEF in tissues from
      azocasein-treated amyloid-resistant rats and CE/J mice excludes the possibility
      that AEF activity may be due to the presence of amyloid fibrils or fibril
      fragments in the donor tissue.

PMID- 8569191
TI  - Proliferation and phenotypic modulation of portal fibroblasts in the early stages
      of cholestatic fibrosis in the rat.
AB  - The animal model of hepatic fibrosis induced by bile duct ligation represents an
      experimental model of human chronic biliary fibrosis. Much attention has been
      given to the hepatic stellate cell (HSC), or perisinusoidal cell, as the source
      of the extracellular matrix proteins. However, in the bile duct ligation model,
      mesenchymal cells other than HSC may be involved in the early stages of fibrosis
      development. The current study examined, in Sprague-Dawley rats, proliferation in
      different liver cell subpopulations as well as expression of alpha-smooth muscle
      (SM) actin and desmin in portal fibroblasts and HSC at 6 hours and 1, 2, 3, and 7
      days after bile duct ligation. Kinetics of liver cell proliferation and of
      phenotypic modulation of portal fibroblasts and HSC (expression of alpha-SM actin
      and desmin) was evaluated by immunocytochemistry, immunofluorescence, and
      immunoelectron microscopy using immunogold technique. In sham-operated animals,
      the evaluation of proliferation in various liver cell subpopulations revealed
      nonsignificant changes compared with nonoperated rats. alpha-SM actin was
      detected in vessel walls but was absent in cells of portal tract and parenchyma.
      Desmin was expressed in vessel walls and in some fibroblastic cells of portal
      stroma (8.2 cells/unit area) as well as in HSC in acinar Zones 1 and 3 (15.6
      cells/unit area and 7.1 cells/unit area, respectively). In bile duct-ligated
      rats, 24 and 48 hours after ligation, marked proliferations of bile duct
      epithelial cells (labeling indices 36.8% and 29.5%, respectively) and of
      periductular fibroblasts (labeling indices 16.7% and 31.0%, respectively) were
      observed; thereafter, proliferation decreased for both populations (labeling
      indices at 7 days 12.0% and 11.6%, respectively). HSC proliferation increased
      gradually until the third day (labeling index 18.6%) and then leveled off.
      Immunocytochemistry and immunoelectron microscopy revealed a significant number
      of cells expressing alpha-SM actin 72 hours after bile duct ligation in the
      stroma adjacent to proliferating ductules. The number of alpha-SM actin-positive
      cells increased until the seventh day (251.6 cells/unit area). At all times
      examined, the distribution of alpha-SM actin was restricted to the connective
      tissue stroma adjacent to proliferating ductules; alpha-SM actin was not
      expressed in HSC of the lobule. An expansion of desmin expression was noted in
      fibroblastic cells in stroma surrounding proliferating ductules until 72 hours
      after bile duct ligation (74.7 cells/unit area) followed by a plateau. At this
      time, desmin expression increased also in HSC; as in controls, the number of
      positive cells was greater in Zone 1 (31.8 cells/unit area) than in Zone 3 (18.5
      cells/unit area). Double immunofluorescence staining detected by confocal
      microscopy showed that the majority of portal fibroblastic cells expressing alpha
      SM actin was desmin negative 48 hours after bile duct ligation. From 72 hours,
      portal fibroblastic cells coexpressing alpha-SM actin and desmin appeared, and
      their proportion increased until 7 days. The present findings indicate that in
      the early phase of bile duct ligation, there is a marked and transient
      proliferation of bile duct epithelial cells associated with proliferation of
      portal periductular fibroblasts, which rapidly express alpha-SM actin. This
      fibroblastic population may play a dominant role in the early portal fibrosis
      after bile duct ligation.

PMID- 8569192
TI  - p53, Ki-ras, and DNA ploidy in human pancreatic ductal adenocarcinomas.
AB  - Ki-ras mutations and DNA aneuploidy are common findings in human pancreatic
      ductal adenocarcinomas. An altered p53 tumor-suppressor gene has been suggested
      to cooperate with activated Ki-ras in malignant cellular transformation and could
      enhance genomic instability. We have investigated a panel of well-documented
      pancreatic carcinomas with defined ploidy and Ki-ras mutations for the presence
      and pattern of genetic alterations of the p53 gene, their coincidence with Ki-ras
      point mutations, and their correlation with DNA ploidy, tumor pathology, and
      clinical course. DNA was isolated from formalin-fixed and paraffin-embedded tumor
      tissue and polymerase-chain-reaction-amplified fragments of the p53 gene exons 5
      to 9 were screened by the single-strand conformation polymorphism method. The
      positive cases were further examined for mutations by direct sequencing. Twenty
      nine of seventy-one (41%) tumors showed mutations of the p53 gene, however, five
      tumors carried two mutations resulting in a total of 34/71 (48%) genetic
      alterations of the p53 gene. The majority were missense point mutations and
      distributed primarily within the evolutionary conserved domains (62%). Ten of
      Thirty-four (29%) affected the hotspot codons 248, 273, and 282, respectively,
      and 21/34 (62%) of the p53 gene mutations clustered on exons 7 and 8. Transitions
      (71%) predominated over transversions (15%), deletions were identified in 7/34
      (21%) tumors. One third of the carcinomas showed both Ki-ras codon 12 and p53
      gene mutations. p53 mutations correlated with distant metastasis (p < 0.05) and
      survival (p < 0.05). DNA triploidy was associated with a mutated Ki-ras gene (p <
      0.05) as well as with double mutations of c-Ki-ras and p53 (p < 0.05). Unlike
      most other malignant tumors pancreatic ductal adenocarcinomas exhibit a
      significantly higher incidence of c-Ki-ras than p53 gene mutations. However, like
      other neoplasms p53 gene mutations seem to be associated with a metastatic
      phenotype possibly acquired during tumor progression.

PMID- 8569193
TI  - In vitro AL-amyloid formation by rat and human mesangial cells.
AB  - AA-amyloid has been produced experimentally in animal models, allowing the study
      of mechanisms involved in AA-amyloidogenesis, but those involved in renal AL
      amyloidogenesis have not been adequately investigated due, in part, to lack of
      appropriate in vitro models. Rat and human mesangial cells were grown on a human
      extracellular matrix (Amgel) derived from normal tissues and on coverslips in the
      presence of 10 microliters of amyloid enhancing factor (AEF) per milliliter of
      media and 10 micrograms/ml monoclonal lambda light chains (LCs) obtained from two
      patients with AL-amyloidosis. Two additional lambda LCs derived from the urine of
      patients with myeloma and tubulointerstitial renal disease were used as controls.
      To verify amyloid deposition, light and electron microscopic examination, as well
      as Congo red and thioflavin T staining, were performed on samples incubated under
      different experimental conditions. Intracellular and extracellular amyloid was
      identified in samples incubated for 24 hours with human mesangial cells (for 48
      hours with rat mesangial cells), amyloidogenic monoclonal LCs, and AEF. The
      amount of amyloid detected, which increased with longer incubation times, was
      found to be most abundant at 14 days. Amyloid was not present in cultures of
      mesangial cells incubated with amyloidogenic LCs alone or in the absence of
      mesangial cells. Likewise, incubation of mesangial cells with amyloidogenic LC or
      AEF separately or amyloidogenic LC in the presence of AEF but without mesangial
      cells did not result in amyloid formation. Amyloid was not seen when LCs obtained
      from the urine of patients with tubulointerstitial renal disease were incubated
      with AEF and mesangial cells. AL-amyloid production requires all three components
      -mesangial cells, amyloidogenic LCs, and AEF. In addition, amyloid was detected
      intracellular in mesangial cells, supporting the hypothesis that the production
      of AL-amyloid in the kidney requires intracellular processing by these cells.
      This system provides a unique experimental model to study renal AL
      amyloidogenesis and a platform to explore mesangial cell-matrix interactions.

PMID- 8569194
TI  - Development and characterization of polarized primary cultures of rat
      intrahepatic bile duct epithelial cells.
AB  - The study of intrahepatic bile duct epithelial cells (i.e., cholangiocytes) has
      been limited by the lack of a polarized in vitro model that allows easy access to
      both apical and basolateral cell surfaces. Therefore, we developed a cell line of
      polarized normal rat cholangiocytes (NRCs) and established conditions that
      produced a confluent monolayer of cells grown on collagen-coated filters of
      tissue culture inserts. We passaged NRCs at high density to collagen-coated,
      tissue-culture inserts and measured transepithelial electrical resistance. We
      evaluated ultrastructural features by transmission and scanning electron
      microscopy. gamma-glutamyl-transpeptidase (gamma GT) was visualized in cultured
      cells by enzyme histochemistry, and cytokeratin (CK)-7, CK-19, vimentin, and
      desmin staining was done by immunohistochemistry. We studied the biologic
      responsiveness and functional polarity of NRCs by measuring their levels of
      cyclic AMP after addition of forskolin with or without somatostatin to either the
      apical or basolateral chambers. When seeded with approximately 1 x 10(5)
      cells/cm2, the NRCs formed a confluent monolayer in 72 hr. Transepithelial
      electrical resistance increased over time, achieving a maximum of 625 (+- 25)
      ohms.cm2 by 1 week after confluence. Transmission and electron microscopy
      scanning showed the apical cell surface to be tightly packed with microvilli with
      a heterogeneous display of cilia ranging from none to 20 to 30 cilia/cell. On
      transmission, apically positioned tight junctions and vesicles were apparent;
      nuclei were oriented basally and the basolateral surface was characterized by
      membrane interdigitations. NRCs stained positively for the cholangiocyte marker
      proteins, gamma-glutamyl-transpeptidase, CK-7, and CK-19, and negative for the
      mesenchymal markers, vimentin, and desmin. Exposure of the basolateral (but not
      the apical) cell surface to somatostatin caused a 60% inhibition of forskolin
      induced increases in intracellular levels of cyclic AMP, suggesting the presence
      of somatostatin receptors exclusively on the basolateral plasma membrane domain.
      We have developed a unique model of primary cultures of normal rat cholangiocytes
      in which the apical and basolateral surfaces are easily accessible; the cells
      develop intermediate-strength tight junctions, retain their cholangiocyte
      phenotype, display morphologic and functional polarity, and are responsive to
      hormones. This model should be useful for the assessment of vectorial transport
      of solutes and other constituents of blood and bile, as well as for studying
      growth regulation of cholangiocytes.

PMID- 8569195
TI  - Levels of cell membrane CD59 regulate the extent of complement-mediated lysis of
      human melanoma cells.
AB  - Normal and neoplastic cells are protected from autologous complement (C) attack
      by different cell-surface C-regulatory proteins including CD59 (protectin), CD46
      (membrane cofactor protein) and CD55 (decay-accelerating factor). Indirect
      immunofluorescence (IIF) analysis showed a differential expression of CD59, CD46,
      and CD55 in nine human melanoma cell lines and that the expression of CD59 was
      highly heterogeneous compared with that of CD46 and CD55. Levels of cell membrane
      CD59 were found to regulate the differential sensitivity of melanoma cells
      investigated to homologous C-mediated lysis; in fact, an inverse correlation (r >
      0.7, p < 0.05) was found between levels of cell membrane CD59, but not of CD46
      and CD55, and extent of C-mediated lysis of melanoma cells sensitized with scalar
      concentrations of the anti-GD3 ganglioside mAb R24. Masking of CD59 by 2.5
      micrograms/ml of the anti-CD59 mAb YTH53.1 induced or enhanced C-mediated lysis
      of melanoma cells sensitized with 2.5 micrograms/ml of mAb R24; the latter
      phenomenon was found to be directly correlated (r > 0.865, p < 0.01) with levels
      of cell membrane CD59. CD59 is bound to melanoma cells by a
      glycosylphosphatidylinositol anchor: treatment of C-resistant melanoma cells Mel
      97, by increasing doses of phosphatidylinositol-specific phospholipase C (PI
      PLC), progressively decreased cell-surface expression of CD59 and increased C
      mediated lysis of cells sensitized with mAb R24. Staining of 38 benign and
      malignant lesions of melanocytic origin by mAb YTH53.1 demonstrated that CD59 is
      consistently expressed in vivo and confirmed the heterogeneous expression
      detected in vitro. Our data, altogether, demonstrate that CD59 is the main
      restriction factor of C-mediated lysis of melanoma cells and that levels of CD59
      may account for their differential resistance to C-mediated lysis. The analysis
      of the levels of CD59 could represent an useful strategy in selecting melanoma
      patients who may benefit from immunotherapeutic treatment(s) that trigger C
      activation.

PMID- 8569196
TI  - Tumor infiltrating lymphocytes in lymph node melanoma metastases: a
      histopathologic prognostic indicator and an expression of local immune response.
AB  - In lymph node melanoma metastases, the expansive proliferation of tumor cells may
      be compared, structurally and cytologically, to the vertical growth phase (VGP)
      observed in primary melanoma. Both in VGP and in nodal metastases, tumor
      infiltrating lymphocytes (TILs) may be present with different patterns. In the
      evaluation of the primary tumor, these patterns have been defined as brisk, non
      brisk, and absent. The histologic slides of regional lymph node metastases, the
      site of first recurrence in 99 consecutive melanoma patients, were reviewed.
      Disease-free survival of these cases and whether or not they were treated with
      rIFN alpha-2A was recorded to identify any relationship among different patterns
      of TILs, therapy, and prognosis. Of 99 cases, 16 were classified as brisk, 37 as
      non-brisk, and 46 as absent. At 30 months of follow-up the disease-free survival
      was 81.3% for brisk cases, 46.8% for non-brisk cases, and 29.3% for absent groups
      (p = .007). Multivariate analysis confirmed the prognostic value of TILs in
      predicting disease-free survival in patients with regional node metastases. The
      difference according to the presence or absence of relapse is particularly
      evident when comparison is made between treated and untreated patients. In
      conclusion the evaluation of first-recurrence regional node melanoma metastases
      for TILs, using the same histopathologic criteria as in VGP of primary melanoma,
      subdivides the cases in brisk, non-brisk, and absent groups. Also, the presence
      of these patterns in metastatic node melanoma deposits is correlatable to disease
      free survival. Our results further stress the difference of prognosis patients
      treated with rIFN alpha-2A compared to the untreated group. The TILs evaluation
      may prove useful in selecting those melanoma stage II patients who will best
      respond to therapy with biologic response modifiers, because the TILs may be the
      local immune effector cell targets of rIFN alpha-2A or of other biologic agents.

PMID- 8569197
TI  - Organ distribution and molecular forms of human xanthine dehydrogenase/xanthine
      oxidase protein.
AB  - Xanthine dehydrogenase/xanthine oxidase (XDH/XO) is a major cytoplasmic source of
      superoxide radicals and hydrogen peroxide, and it is considered important in the
      pathogenesis of ischemia-reperfusion damage. Because little is known about the
      enzyme in human tissues, the aims of this study were to purify human XDH/XO and
      to produce Ab for detection of the protein in Western blots and for
      quantification by ELISA. We purified human milk XDH/XO, produced Ab for Western
      blotting and ELISA of the protein, and evaluated the molecular forms and activity
      protein relationships in human tissues. The molecular size of the purified
      protein under nondenaturing conditions was approximately 300 kd. On SDS-PAGE, it
      was fragmented into four main bands of 143, 125, 87, and 59 kd. Ab recognized
      bands of similar size in Western blots of the purified preparation and human
      milk. In fresh liver homogenates treated with anti-proteases, the three largest
      bands were observed; in the intestine, only the two largest were observed. Serum,
      brain, heart, and skeletal muscle were negative, whereas some lung and kidney
      samples showed one faint band of 143 kd. Trypsin treatment of the enzyme
      converted the large molecular-weight bands into smaller bands, as did incubation
      of a liver homogenate without anti-proteases. XDH/XO protein concentrations
      (ng/mg total protein) were 146 +/- 70 in liver and 556 +/- 320 in intestine and
      less than 5 ng/ml in serum. The relationship of activity to protein (2.7-3.0
      mumol/min/mg XDH/XO protein) was constant in liver and intestine during
      development. We conclude that 1) human XDH/XO has molecular size and subunit
      structure similar to other mammalian enzymes; 2) the polypeptide chain is
      unstable, also in the intact cell, despite retained activity; and 3) the amount
      of inactive XDH/XO in human liver and intestine is apparently small.

PMID- 8569198
TI  - Serum-mediated resolution of Lyme arthritis in mice.
AB  - Arthritis and carditis were mildly improved upon adoptive transfer of T cell
      enriched lymphocyte populations from Borrelia burgdorferi-infected (B.
      burgdorferi) (immune) compared with naive immunocompetent mice into B.
      burgdorferi-infected, severe combined immunodeficient (SCID) mice. Despite the
      relative purity of T cells in transferred cells, recipient mice seroconverted to
      B. burgdorferi. Thus, the effect could not be attributed to T cells alone.
      Passive transfer of serum from actively infected immunocompetent mice (immune
      serum) to SCID mice at the time of or before B. burgdorferi inoculation, or on
      Days 4, 8, and 12 after inoculation prevented or cured (respectively) infection
      and disease when examined at 15 days. Transfer of immune serum on Days 12, 16,
      20, 24, and 28 did not clear infection at Day 30 but resulted in resolution of
      arthritis, indicating that immune serum can cause resolution of joint disease.
      Immune serum treatment could maintain arthritis resolution for up to 60 days.
      Immune serum from mice infected for 90 days or 15 months both had strong
      protective, post-infection, and arthritis-modulating activity, whereas
      hyperimmune serum to heat-killed B. burgdorferi or recombinant outer surface
      protein (Osp) A protected mice against infection when given on Day 0--but not at
      later intervals--and did not modulate disease. Immune serum from 90-day infected
      mice labeled spirochetes in joint tissues of SCID mice by immunohistochemistry,
      but hyperimmune serum to heat-killed B. burgdorferi or OspA did not. These
      studies suggest that the biologically active properties of immune serum may be
      directed toward yet to be defined, in vivo-expressed antigens of B. burgdorferi.

PMID- 8569199
TI  - The temporal and spatial vascular endothelial growth factor expression in retinal
      vasculogenesis of rat neonates.
AB  - Vascular endothelial growth factor (VEGF) has been identified as an endothelial
      cell-specific mitogen with potent angiogenic properties. VEGF is overexpressed in
      pathologic angiogenesis observed in tumor growth, rheumatoid arthritis, and
      retinal angiogenic diseases such as diabetic retinopathy and retinopathy of
      prematurity. VEGF expression in physiologic angiogenesis, i.e., vasculogenesis,
      has also been reported in the embryonic organs such as brain, kidney, spleen, and
      lung. However, the details of VEGF expression in vasculogenesis remain largely
      unclear. To determine if VEGF contributes to vasculogenesis in the developing
      tissues, VEGF expression was studied by both immunohistochemistry and in situ
      hybridization in newborn rat retinas on postnatal days 3, 7, 14, and 30.
      Vasculogenesis was assessed by both the ink perfusion method and a histologic
      examination. To identify the cell types of VEGF-expressing cells,
      immunohistochemistry for cell markers such as glial fibrillary acidic protein and
      von Willebrand factor was performed. On postnatal days 3 and 7, when retinal
      vasculogenesis was active, VEGF mRNA and protein(s) were prominently expressed in
      the ganglion cell and the inner nuclear layers. In rats, as well as humans, these
      two layers are where the retinal vessels develop, and these two layers depend
      solely on the retinal vessels. In addition to the ganglion and the inner nuclear
      layers, VEGF protein(s) were located in the endothelial cells of the developing
      vessels and the angioblasts, i.e., endothelial precursors. On postnatal day 14,
      when vasculogenesis became inactive, VEGF mRNA expression markedly decreased.
      These results indicated that VEGF expression in the developing retinas is
      temporally and spatially correlated with retinal vasculogenesis.

PMID- 8569200
TI  - Morphologic basis of the functional gastric acid barrier.
AB  - The gastric mucosa possesses a functional barrier that prevents intrusion of
      luminal acid. The aim of the present study was to elucidate the morphologic basis
      of this barrier by exploring the effect of acid challenge on the gastric mucosal
      epithelium, basal lamina, and microvasculature. The stomachs of urethane
      anesthetized rats were perfused, for at least 45 minutes, with 0.05 M HCl or 0.15
      M HCl in the absence or presence of the mucosal barrier breaker ethanol (15%) and
      examined by light, scanning, and transmission electron microscopy. Gastric
      perfusion with 0.05 M HCl alone caused superficial cell injury, the damaged
      surface cells loosing the surface membrane, whereas the junctional complex and
      basolateral membrane were preserved. Perfusion of 0.15 M HCl alone led to focal
      ablation of surface epithelial cells in the interfoveolar regions, and cells in
      the gastric pits remained grossly normal. Exposure to the barrier breaker ethanol
      (15%) in the presence of 0.05 M HCl caused extensive ablation of the surface
      epithelium. There were many focal areas in which the honeycomb structure of the
      lamina propria was exposed and the basal lamina was removed. Gastric mucosal
      damage progressed further when the luminal HCl concentration was raised to 0.15 M
      in the presence of ethanol (15%). In this instance, extensive areas with deep
      erosions and vast areas of deep-reaching ablation of the epithelium and basal
      lamina were observed. Ultrastructurally, there was extensive damage to the
      endothelium of capillaries lying underneath denuded areas of the gastric mucosa,
      the injured capillaries containing erythrocyte ghosts and thrombocyte aggregates.
      The data suggest that the integrity of the junctional complex, basolateral
      membrane, and basal lamina forms the morphologic basis of the functional gastric
      acid barrier. Once these structures are disrupted or ablated to an appreciable
      extent, damage forms in the mucosal microvasculature, and injury progresses to
      deeper layers of the mucosa.

PMID- 8569202
TI  - Benefits and challenges of school-based crisis response teams.
AB  - Given the increasing prevalence of schoolchildren's experience with crises and
      resulting loss through sudden or violent death, adoption of a school-based crisis
      prevention and response plan becomes crucial. This article reviews a model of
      regional, district, and school-based levels of response designed collaboratively
      by four school districts and consultants from Yale University. The team approach
      on which the model is based is examined through benefits it affords students,
      staff, parents, and the community. Obstacles that can impede full implementation
      of the model are identified, and strategies for overcoming logistical and
      systemic resistances are offered. This proactive design helps promote individual
      and organizational resiliency to traumatic events by promoting communication,
      collaboration, and service provision in an efficient and comprehensive manner.

PMID- 8569201
TI  - Apoptotic and necrotic myocyte cell deaths are independent contributing variables
      of infarct size in rats.
AB  - Programmed cell death in the myocardium has been linked to ischemia reperfusion
      injury as well as to excessive mechanical forces associated with increases in
      ventricular loading. Moreover, hypoxia activates the suicide program of cardiac
      myocytes in vitro. Because the supplied portion of the ventricular wall is
      ischemic and subjected to high levels of systolic and diastolic stresses (acutely
      after coronary artery occlusion), apoptosis and necrosis may contribute
      independently to myocyte cell death after infarction. Therefore, myocardial
      infarction was produced in rats, and, after the determination of ventricular
      hemodynamics, the contribution of apoptotic and/or necrotic myocyte cell death to
      infarct size was measured quantitatively from 20 minutes to 7 days after coronary
      artery occlusion. Programmed cell death was assessed by the terminal
      deoxynucleotidyl transferase assay and by the electrophoretic detection of DNA
      laddering. Myocyte necrosis was evaluated by myosin monoclonal Ab labeling.
      Moreover, the expression of Bcl-2, Bax, and Fas proteins in myocytes was examined
      by immunocytochemistry. Myocyte cell death by apoptosis and necrosis comprised
      nearly 3 million myocytes at 2 hours. Apoptotic cell death involved 2.8 million
      cells and necrotic cell death only 90,000 myocytes. Apoptosis continued to
      represent the major independent form of myocyte cell death, affecting 6.6 million
      myocytes at 4.5 hours. Myocyte necrosis peaked at 1 day, including 1.1 million
      myocytes. DNA electrophoretic analysis confirmed these observations by showing
      nucleosomal ladders at 2-3 hours, 4.5 hours, 1 day, and 2 days after coronary
      artery occlusion. Myocytes showing both DNA strand breaks and myosin labeling
      were a prominent aspect of myocardial damage only after 6 hours. Finally, the
      expression of Bcl-2 and Fas in myocytes increased 18-fold and 131-fold,
      respectively. In conclusion, programmed myocyte cell death is the major form of
      myocardial damage produced by occlusion of a major epicardial coronary artery,
      whereas necrotic myocyte cell death follows apoptosis and contributes to the
      progressive loss of cells with time after infarction. The enhanced expression of
      Fas may be implicated in the activation of apoptosis in spite of the increase in
      Bcl-2, which tends to preserve cell survival.

PMID- 8569203
TI  - The Claxton Elementary School Health Program: merging perceptions and behaviors
      to identify problems.
AB  - The Claxton Elementary School Health Program was developed to improve the health
      of a school community in a western North Carolina city of 60,000. Using the
      principles of Community-Oriented Primary Care (COPC) in fall 1991, a health
      advisory board composed of interested parents, teachers, and physicians was
      organized. A comprehensive needs assessment was implemented, including focus
      groups with teachers and parents, a self-administered health behavior survey for
      children in grades three-five, and a self-administered survey of parents' health
      problems. Teachers, children, and parents agreed on perceived problems requiring
      attention. The Board then prioritized health problems, selecting nutrition and
      self-concept as the most critical areas in which to develop programs. Using
      target population members to identify needs can be a valuable approach to the
      development of community-based programs for improving children's health
      behaviors.

PMID- 8569204
TI  - Factors associated with the stages of alcohol use among inner city school youth.
AB  - This study explored stages of alcohol acquisition and risk-factors associated
      with stages based on the Multi-Component Motivational Stages model. Two hundred
      fifty-four sixth-eighth grade students from an urban school completed a
      confidential questionnaire. Most students were in a precontemplation stage (86%),
      preparation stage (6%), or action stage (5%) for alcohol use. Significant
      differences were found across stage status on 11 of 22 risk factors. Discriminant
      analysis results indicated alcohol use, perceived prevalence of alcohol
      consumption, and intentions to drink in the future successfully discriminated
      youth in action and preparation from those in precontemplation and contemplation
      stages. Meanwhile, tobacco use discriminated students in preparation and action
      stages. Multiple regression analysis showed alcohol use was the most powerful
      predictor of acquisition stage status, followed by intentions, influenceability,
      and perceived severity of alcohol use. Implications for school-aged youth alcohol
      use prevention are discussed.

PMID- 8569205
TI  - Using administrative data to identify elementary schools at increased risk for
      student absences.
AB  - The ability to use administrative databases to identify elementary schools at
      risk for high percentages of school absence may prove useful in targeting
      elementary schools to receive absence reduction interventions. This report
      demonstrates an analysis method using existing administrative data for generating
      relative risks. Taking advantage of administrative databases can save resources
      and assist efforts in developing ways to reduce elementary school absence.

PMID- 8569206
TI  - Amber, Katie, and Ryan: lessons from children with complex medical conditions.

PMID- 8569207
TI  - Suicide among children, adolescents, and young adults--United States, 1980-1992.

PMID- 8569208
TI  - Intrarenal infusions of endothelin in conscious dogs: interactions with
      prostanoids and angiotensin II.
AB  - Endothelin (2, 5, and 10 pmol/kg/min) was infused into the renal artery of
      conscious dogs, producing graded and progressive reductions in renal blood flow
      (RBF) without initial vasodilatation, parallel reductions in glomerular
      filtration rate (GFR), and reduced Na+ excretion, but little change in urine
      flow. Pretreatment of the dogs with either ibuprofen (20 mg/kg orally) or aspirin
      (30 mg/kg p.o.) did not significantly alter the effects of endothelin (5
      pmol/kg/min) on RBF, GFR, or Na+ excretion. However, endothelin caused
      antidiuresis in these cyclooxygenase-inhibited dogs, indicating that the effects
      of endothelin on water reabsorption were prostanoid mediated. Treatment with
      captopril (1.5 mg/kg + 0.5 mg/kg/h) did not significantly alter any of the
      responses to endothelin. The local effects of endothelin in the kidneys of
      conscious dogs were vasoconstriction and reduced Na+ excretion which were not
      mediated or modified by either angiotensin II or prostanoids.

PMID- 8569209
TI  - Influence of indapamide and chlorthalidone on reperfusion-induced ventricular
      fibrillation in isolated guinea pig hearts.
AB  - The delayed rectifier potassium current (IK) is a major repolarizing current in
      guinea pig ventricular myocytes. Blockade of IK or other repolarizing currents is
      of increasing interest for development of antiarrhythmic drugs; however, these
      interventions may also be proarrhythmic. In the present study, we compared the
      potential antiarrhythmic properties of indapamide and chlorthalidone, two
      structurally related sulfonamide diuretics which differ in their ability to block
      the slow component of the delayed rectifier (IKs) in isolated, buffer-perfused
      guinea pig hearts. Hearts underwent 30-min global no-flow ischemia and 10-min
      reperfusion. Dose-response (10(-7)-10(-4) M) effects of indapamide or
      chlorthalidone on reperfusion-induced arrhythmias, coronary flow, and heart rate
      (HR) were evaluated in a randomized blinded fashion. There was no significant
      difference in the incidence of ventricular fibrillation (VF) for either compound
      as compared with untreated controls. However, VF duration was reduced to < 40 s
      in all hearts treated with indapamide 10(-4) M). Mean VF duration with indapamide
      10(-4) M was 31 +/- 4 versus 70 +/- 40 s in controls (p < 0.05). Chlorthalidone
      did not protect against reperfusion-induced arrhythmias. HR was unchanged with
      either compound; coronary flow during the control perfusion period increased
      approximately 43% with indapamide 10(-4) M (p < 0.05 vs. all treatment groups).
      These results demonstrate that indapamide, but not chlorthalidone, confers
      significant protection against reperfusion-induced VF in this experimental
      preparation and suggest that selective block of IKs may be antiarrhythmic.

PMID- 8569210
TI  - Are intracardiac electrophysiological studies in healthy volunteers ethical? Time
      for multinational recommendations.

PMID- 8569211
TI  - The ethical issue--not only healthy volunteers!

PMID- 8569212
TI  - Selective Ik blocker almokalant exhibits class III--specific effects on the
      repolarization and refractoriness of the human heart: a study of healthy
      volunteers using right ventricular monophasic action potential recordings.
AB  - Almokalant, a recently developed potassium-channel blocker, has exhibited
      properties of a selective class III agent in vitro and in animal experiments. We
      report the first invasive study in humans in which the electrophysiological
      characteristics of almokalant were assessed. Thirty-four healthy males received
      bolus and maintenance infusions of almokalant to two of our target plasma
      concentrations of 20, 50, 100, and 150 nM. Electrophysiological variables were
      assessed during stimulation at 100 and 120 beats/min at baseline and at two
      consecutive targeted levels. Almokalant dose-dependently increased the duration
      of the monophasic action potential (MAP) above a mean plasma concentration of 60
      nM. The duration at 90% repolarization significantly increased by 20% from
      baseline at 100 beats/min (p < 0.00005), and by 19% at 120 beats/min (p <
      0.00005), at a mean plasma concentration of 116 nM. During atrial stimulation,
      there was a significant increase in the QT interval, amounting to 24% at 100
      beats/min (p < 0.00005) and to 30% at 120 beats/min (p = 0.0006), at 124 nM.
      During right ventricular stimulation in the apical region, the QT interval
      significantly increased by 17% at 100 beats/min (p < 0.00005), and 13% at 120
      beats/min (p < 0.00005). During stimulation from the right ventricular outflow
      tract, the QT interval increased to a lesser extent and significantly only at 120
      beats/min: 9% at 100 beats/min (p = NS) and 6% at 120 beats/min (p = 0.001) at
      118 nM. The effective refractory period (ERP) of the atria increased by 18% at
      100 beats/min at 119 nM (p = 0.005). The right ventricular ERP increased by 16%
      at both heart rates (HR) (p < 0.00005) during stimulation from the apical region,
      and by 11% during stimulation from the outflow tract (p = 0.0001 at 100 beats/min
      and p = 0.0006 at 120 beats/min). There was no effect on the ERP of the
      atrioventricular node, (AVN) on the sinus node function or cardiac conduction.
      Two individuals experienced a transient metallic taste during bolus infusion
      aiming at 50 and 100 nM, but this side effect did not occur in the group
      receiving the highest doses. Pronounced T-wave/U-wave (TU) morphology changes
      were observed in 4 individuals. Almokalant exhibited characteristics of a pure
      class III agent with no effects on cardiac conduction or sinus node function when
      given intravenously. Although no proarrhythmias were observed, the development of
      TU morphology changes and increased spatial dispersion of repolarization after
      the highest doses warrants further studies regarding the safety profile of the
      drug.

PMID- 8569214
TI  - Effects of vasopressin V1 and V2 receptor antagonists on the development of salt
      induced hypertension in Dahl rats.
AB  - To determine whether the vasopressor and antidiuretic actions of arginine
      vasopressin (AVP) may participate in the development of salt-induced
      hypertension, we examined the long-term effects of AVP V1 and V2 receptor
      antagonists on blood pressure (BP) in Dahl-Iwai salt-sensitive (DS) and salt
      resistant (DR) rats. From age 7 weeks, DS and DR rats were fed a diet containing
      8% NaCl, alone (control group); 8% NaCl and 1% OPC-21268 (V1 antagonist-treated
      group); or 8% NaCl and 0.05% OPC-31260 (V2 antagonist-treated group). The pressor
      response to AVP was significantly inhibited in DS rats treated with OPC-21268.
      Urinary volume and water intake were significantly increased by administration of
      OPC-31260; this increase was greater in DR rats than in DS rats. Indirect BP
      measurements obtained using tailcuff plethysmography showed that DS but not DR
      rats developed hypertension when fed high-salt diets. However, chronic treatment
      with either OPC-21268 or OPC-31260 did not alter the course of hypertension in DS
      rats, despite the effective blocking actions of these antagonists. This finding
      also was confirmed by direct BP measurements. Our results indicate that even if
      AVP plays a role in salt-induced hypertension peripheral blockade of either
      subtype of AVP receptors does not prevent the development of hypertension in DS
      rats.

PMID- 8569213
TI  - Vasodilatory effect of nicorandil on coronary arterial microvessels: its
      dependency on vessel size and the involvement of the ATP-sensitive potassium
      channels.
AB  - We aimed to clarify the size dependency of nicorandil-induced dilation in
      coronary microcirculation and the involvement of adenosine triphosphate (ATP)
      sensitive potassium channels. Coronary arterial microvessels were observed
      through a microscope equipped with a floating objective in anesthetized open
      chest dogs (n = 29). Heart rate and mean aortic pressure were maintained at
      control level. In 16 dogs, nicorandil was infused into the coronary in a
      cumulative fashion (0.1, 1.0, 10, and 100 micrograms/kg/min, for 5 min for each
      dose). In 13 dogs, glibenclamide (10 microM) was topically applied onto the
      observed area, and nicorandil was similarly infused. Nicorandil dilated vessels <
      100 microns in diameter at all applied doses in a dose-dependent manner.
      Glibenclamide abolished the dilation of these vessels at the lower two doses.
      Vessels > 100 microns in diameter dilated only at the two higher doses and the
      dilation was not affected by glibenclamide. These data suggest that the vessels <
      100 microns are more sensitive to this agent than other size vessels, and that
      ATP-sensitive potassium channels are involved in the nicorandil-induced dilation
      of vessels smaller than 100 microns, whereas the dilation of other size vessels
      occurs independently of this channel.

PMID- 8569215
TI  - Coronary and systemic hemodynamic effects of the putative nitric oxide donor, FK
      409, in comparison with nitroglycerin in conscious and anesthetized dogs.
AB  - We compared, the hemodynamic profile of FK 409, a new nitric oxide (NO) donor,
      directly with that of nitroglycerin (NTG) in chloralose-anesthetized dogs and in
      chronically instrumented conscious dogs. In anesthetized dogs, FK 409 and NTG
      (each 0.03-30 micrograms kg-1, intravenously, i.v.) both dilated large and small
      coronary arteries dose dependently. This coronary vasodilation was associated
      with dose-dependent decreases in blood pressure (BP), total peripheral resistance
      (TPR), and left ventricular end-diastolic pressure (LVEDP) and with increases in
      cardiac output (CO), heart rate (HR) and dP/dtmax. FK 409 was equipotent to NTG
      in dilating large coronary arteries and in reducing cardiac preload, but three
      times less potent as systemic and coronary arteriolar vasodilator. In general,
      the effects of FK 409 developed more slowly and lasted longer than those of NTG.
      With both drugs, dilation of large coronary arteries was sustained as compared
      with dilation of systemic or coronary arterioles. In conscious dogs, coronary and
      systemic hemodynamic effects of FK 409 and NTG (each 0.1-10 micrograms kg-1 i.v.)
      were qualitatively and quantitatively very similar to those observed in
      anesthetized dogs, except that reflex tachycardia was more pronounced in animals
      in the conscious state. Administered orally, FK 409 (0.3 mg kg-1) produced a
      marked and preferential vasodilation of large coronary arteries but had only
      minor effects on BP and HR. Coronary blood flow (CBF) was unchanged. FK 409 is an
      orally active vasodilator with a hemodynamic profile similar to that of NTG. FK
      409 exhibits a slightly higher selectivity for large epicardial coronary arteries
      and has a longer duration of action than NTG.

PMID- 8569216
TI  - Renal responses to angiotensin receptor antagonist and angiotensin-converting
      enzyme inhibitor in partially nephrectomized spontaneously hypertensive rats.
AB  - To investigate the role of the renin-angiotensin system (RAS) on nephrosclerosis
      in salt-loaded, partially nephrectomized spontaneously hypertensive rats (SHR),
      we evaluated the effects of angiotensin II (ANGII) blockade on the progression of
      nephrosclerosis with an angiotensin type 1 receptor (AT1rec) antagonist [TCV-116
      (TCV)] and an angiotensin-converting enzyme (ACE) inhibitor (enalapril) at the
      doses equivalent in reducing systemic blood pressure (BP). SHR were five/sixths
      nephrectomized and were fed a high-salt diet. In addition to being significantly
      preventive against an increase in systolic BP, both TCV and enalapril
      significantly attenuated the increases in proteinuria and the renal
      histopathological alterations. Transcription of AT1rec mRNA in the remnant kidney
      was enhanced with the progression of nephrosclerosis, but was inhibited by TCV as
      well as enalapril. In these aspects, there were no apparent differences between
      effects of TCV and enalapril. The RAS system plays an important role in
      nephrosclerosis in partially nephrectomized SHR despite a high-salt diet, and
      direct ANGII blockade certainly protected the kidney against hypertensive injury
      in this model.

PMID- 8569217
TI  - Effects of a new amiodarone-like agent, SR 33589, in comparison to amiodarone,
      D,L-sotalol, and lignocaine, on ischemia-induced ventricular arrhythmias in
      anesthetized pigs.
AB  - We compared the ability of a new amiodarone-like agent, SR 33589, with that of
      amiodarone, D,L-sotalol, and lignocaine to reduce the incidence of ventricular
      fibrillation (VF) and associated arrhythmias caused by acute coronary artery
      occlusion in anesthetized pigs. Ischemia was induced by occlusion of the left
      coronary descending artery (LAD) for 30 min. Premature ventricular complexes
      (PVCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) were
      recorded during coronary occlusion. SR 33589 (1.25, 2.50, and 5 mg/kg
      intravenously, i.v.) markedly reduced the occurrence of ventricular arrhythmias
      during ischemia. The incidence of VF was reduced from 90% in the control group to
      30% (p < 0.05) with 1.25 mg/kg, to 10% (p < 0.001) with 2.50 mg/kg, and to 20% (p
      < 0.01) with 5 mg/kg. In addition, SR 33589, especially at the two higher doses,
      caused a sustained reduction in both the incidence of VT and the number of PVCs
      per minute. In comparison, amiodarone 10 and 20 mg/kg i.v. reduced the incidence
      of VF (40 and 50%, respectively), but these reductions never reached a level of
      statistical significance. The incidence of VT and the number of PVCs per minute
      were also decreased significantly by amiodarone. D,L-sotalol 3 mg/kg i.v. exerted
      significant anti-arrhythmic activity; the incidence of VF was reduced 20% (p <
      0.01), and both the incidence of VT and number of PVC per minute were also
      reduced. In contrast, lignocaine given as a 2-mg/kg bolus followed by an infusion
      at 70 micrograms/kg/min had no antiarrhythmic or antifibrillatory activity in
      this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8569219
TI  - Effects of chronic norepinephrine administration on cardiac function in rats.
AB  - We assessed the changes in the contractile response of rat hearts in vivo after
      chronic exposure to a range of doses of norepinephrine (NE) and determined
      whether free radical production played a role in these changes. Osmotic minipumps
      were implanted subcutaneously (s.c.) in male rats and delivered either NE (0.15
      0.35 mg/kg/h) or acid saline for 10-28 days. The animals were then anaesthetised
      and prepared for haemodynamic measurement, and dose-response curves to acutely
      administered NE and calcium chloride were constructed. We analysed plasma for
      evidence of free radical activity by measuring the levels of thiobarbituric acid
      reactive substances (TBARS). All doses of NE studied produced left, but not
      right, ventricular hypertrophy. Treatment with 0.25 mg/kg/h NE for 28 days
      produced signs of distress and, by 10 days, treatment with 0.35 mg/kg/h resulted
      in 33% mortality. Treatment with the two lower doses, but not the highest dose,
      of NE resulted in increases in basal left ventricular (LV) maximum rate of
      pressure generation and a marked increase in systolic, but not diastolic,
      arterial blood pressure (SBP, DBP). All doses of NE caused reduced responses to
      acutely administered NE but no marked change in the response to calcium chloride.
      Levels of plasma free radicals were increased only with the highest dose of NE.
      Over the concentration range studied, chronic administration of NE to rats causes
      beta-adrenoceptor downregulation and free radical production was associated only
      with the administration of a dose of NE that resulted in high mortality.

PMID- 8569218
TI  - Failure of calcium channel blockade to reduce platelet-mediated cyclic flow
      variations in dogs with coronary stenosis and endothelial injury.
AB  - Experimental canine coronary artery stenosis associated with endothelial injury
      results in a typical pattern of coronary flow characterized by gradual decreases
      in blood flow to almost zero values followed by abrupt restorations to original
      levels. Cyclic flow variations (CFVs) are the consequence of recurrent platelet
      aggregation at the site of the stenosis and subsequent dislodgement of the
      thrombus. The present study was designed to test the efficacy of diltiazem,
      nifedipine, and verapamil in inhibiting in vivo platelet aggregation as compared
      with that of aspirin and ketanserin, two potent reference compounds effective in
      this model. Except for aspirin, compounds were given as a slow intravenous
      infusion (i.v.) for 60 min to avoid hemodynamic changes. Diltiazem (0.01
      mg/kg/min), nifedipine (3 micrograms/kg/min), and verapamil (0.01 mg/kg/min) were
      totally inactive against CFVs. A higher dose of verapamil (0.02 mg/kg/min)
      abolished CFVs in 3 of 4 dogs, but serious side effects were observed
      [atrioventricular (AV) block and death of 2 animals]. Aspirin (10 mg/kg bolus)
      caused complete inhibition of CFVs in 4 of 4 dogs, and ketanserin (0.01
      mg/kg/min) abolished CFVs in 4 of 5 dogs. These data suggest that calcium channel
      blockade alone in contrast to cyclooxygenase inhibition or 5-HT2 antagonism
      cannot inhibit thrombus formation in this model.

PMID- 8569220
TI  - Effect of nifedipine on cyclic GMP turnover in cultured coronary smooth muscle
      cells.
AB  - We investigated the effects of nifedipine on cyclic GMP turnover and the
      pertinent enzyme activities in cultured coronary smooth muscle cells (SMC).
      Nifedipine at high concentrations slightly decreased basal soluble guanylate
      cyclase activity and inhibited the action of sodium nitroprusside (SNP) but had
      no effect on the particulate form of the enzyme. In contrast, nifedipine
      inhibited cyclic GMP hydrolysis by directly inhibiting the partially purified
      calmodulin-stimulated isoform of phosphodiesterase (type I PDE) with IC50 of 4.2
      microM. Nifedipine > or = 1.0 microM enhanced cyclic GMP accumulation in response
      to 1.0 microM SNP, although nifedipine alone exerted no influence on cyclic GMP
      levels. Enhancement of cyclic GMP accumulation by nifedipine in response to SNP
      was not affected by BAY K 8644, a calcium channel agonist. These properties may
      be shared by other dihydropyridines since nicardipine and nisoldipine also
      inhibited type I PDE with similar IC50. However, some other structurally
      unrelated calcium channel blockers, diltiazem and verapamil, had little effect on
      cyclic nucleotide hydrolysis or on cyclic GMP accumulation in response to SNP.
      Nifedipine may synergistically enhance cyclic GMP accumulation in response to
      nitric oxide (NO)-releasing agents by directly inhibiting type I PDE in coronary
      SMC. Such effects of nifedipine may partly contribute to coronary vasodilation
      and prevention of coronary spasm in patients with ischemic heart disease.

PMID- 8569221
TI  - Degree of external force to the left ventricle determines hemodynamic response to
      nitroprusside in failing hearts: comparison with the response to dobutamine.
AB  - Vasodilators frequently, although not always, increase cardiac output (CO) in
      patients with congestive heart failure (CHF) despite a decrease in left
      ventricular (LV) diastolic pressure. In patients with CHF, vasodilator-induced
      decrease in LV diastolic pressure without decrease in "preload" plays an
      important role in the vasodilator-induced increase in CO failure that may be
      caused by a vasodilator-induced reduction in external force to the LV. To clarify
      the hypothesis that a hemodynamic response to vasodilators depends on the degree
      of external force to the LV in failing hearts before drug administration and to
      examine whether the degree of the external force also affects a hemodynamic
      response to positive inotropic agents, we produced in 17 dogs two different
      conditions of LV dysfunction with high LV end-diastolic pressure (EDP: > or = 15
      mm Hg), i.e., 1 with high right ventricular (RV) EDP (condition 1) and the other
      with lower RVEDP than condition 1 (condition 2), and compared hemodynamic effects
      of nitroprusside or dobutamine between these two conditions. Condition 1 was
      produced by the injection of a small dose of microspheres into the left coronary
      artery and intravenous infusion of dextran. Condition 2 was produced only by the
      injection of a large dose of microspheres. The nitroprusside-induced decrease in
      LVEDP was associated with a greater decrease in RVEDP and lesser decreases in
      mean left atrial pressure and LV end-diastolic diameter in condition 1 than in
      condition 2. CO increased in condition 1; however, CO then decreased in condition
      2. The nitroprusside-induced changes in CO inversely correlated with those in
      RVEDP (r = 0.65, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8569222
TI  - Beneficial effects of beraprost sodium, a stable prostacyclin analogue, in
      diabetic cardiomyopathy.
AB  - We examined whether beraprost sodium (beraprost), a stable prostacyclin analogue,
      prevented cardiomyopathy in diabetic rats in vivo. Diabetes was induced by a
      bolus injection of streptozotocin in rat-tail vein. Four weeks after the
      induction of diabetes, the animals were treated with beraprost (30
      micrograms/kg/day, p.o.) for 4 weeks until they were used for the measurement of
      hemodynamics, electrocardiogram (ECG), and plasma creatine phosphokinase (CK)
      activity. Nontreated diabetic rats have lower mean blood pressure, heart rate,
      left ventricular systolic pressure, and peak positive dP/dt at basal levels
      compared to age-matched normal rats. All of these changes were not improved in
      beraprost-treated rats. The left ventricular end-diastolic pressure and ST/R
      ratio in the ECG were significantly increased in diabetic rats. These parameters
      were significantly improved by beraprost compared with nontreated diabetic rats.
      Additionally, beraprost significantly suppressed the elevation of plasma CK
      activity as compared with that in non-treated diabetic rats. Changes in peak
      positive dP/dt in response to isoproterenol were attenuated in nontreated
      diabetic rats as compared with age-matched normal rats and beraprost-treated
      diabetic rats. These results suggest that beraprost is capable of preventing
      diabetic cardiomyopathy without affecting hyperglycemic condition.

PMID- 8569223
TI  - K+ channel-opening properties of a novel compound, NIP-121, in guinea pig
      myocardium as compared with those of cromakalim.
AB  - Myocardial effects of NIP-121, a novel compound with potent vasorelaxant
      activity, were examined in comparison with those of cromakalim in isolated tissue
      and cells from guinea pig hearts. NIP-121 and cromakalim concentration
      dependently reduced the action potential duration (APD) of isolated papillary
      muscle; the effect was antagonized by glibenclamide. In isolated ventricular
      tissue, NIP-121 and cromakalim decreased the contractile force concentration
      dependently. In these two experiments, the potency of NIP-121 was approximately
      20 times higher than that of cromakalim. The effects of NIP-121 and cromakalim on
      membrane currents were examined in voltage-clamped ventricular myocytes. NIP-121
      (10(-6) M) and cromakalim (3 x 10(-5) M) increased the steady-state outward
      currents. The normal inwardly rectifying current-voltage relationship changed to
      a linear relationship that reversed at the K+ current reversal potential. The
      current activated by NIP-121 and cromakalim was inhibited either by glibenclamide
      or by increased intracellular ATP concentration. NIP-121, at this concentration,
      had little effect on the calcium current. Thus, NIP-121 was demonstrated to
      produce AP shortening and decrease in contractile force through activation of ATP
      sensitive K+ currents in cardiac muscle, with a potency approximately 20 times
      higher than that of cromakalim.

PMID- 8569224
TI  - Effect of angiotensin-converting enzyme inhibition on intimal thickening in
      rabbit collared carotid artery.
AB  - The positioning of a nonocclusive silicone collar around the rabbit carotid
      artery results in the formation of a neointima under a morphologically continuous
      endothelium. We wished to determine whether oral treatment with angiotensin
      converting enzyme (ACE) inhibitors prevents or retards intimal thickening and
      whether this is related to the blood pressure (BP) lowering effects of such
      drugs. Silicone collars were placed around the left carotid artery of 104 male
      New Zealand white rabbits for 14 days. The contralateral carotid artery was sham
      operated. Three ACE inhibitors were administered from 7 days before collar
      placement until the end of the experiment: zabicipril (0, 0.03, 0.10, or 0.30
      mg/kg/day), moexipril (0, 0.3, 1, or 3 mg/kg twice daily, b.i.d.), and enalapril
      (0 or 3 mg/kg/day). Each group consisted of 6-12 animals. BP and plasma ACE
      activity were measured in the nonanesthetized rabbits after 3-week treatment. To
      evaluate intimal thickening, we measured the cross-sectional area of intima and
      media. The positioning of the collar led to significant intimal thickening after
      14 days. Although the ACE inhibitors decreased BP (zabicipril, 9, 16, 16%;
      moexipril, 10, 22, 31%; enalapril, 15%) and plasma ACE activity (zabicipril, 87,
      88, 92%; moexipril, 79, 92, 93%; enalapril, 88%) significantly and dose
      dependently, they did not reduce intimal thickening or the cross-sectional area
      of the media. Angiotensin II does not play a dominant role in collar-induced
      intimal thickening in rabbits. Furthermore, reducing the BP of normotensive
      rabbits does not alter neointima formation in this model.

PMID- 8569225
TI  - Ketanserin lowers erythropoietin concentration in hemodialyzed patients treated
      with the hormone.
AB  - Ketanserin, an antagonist of peripheral serotonin receptors when given to
      hemodialyzed patients treated with recombinant human erythropoietin (rHuEpo)
      corrects some changes in hemostasis but also apparently delays an increase in
      hematocrit. We wished to elucidate the effects of oral administration of
      ketanserin on serum Epo, some hematological and biochemical blood parameters,
      arterial blood pressure (BP), and bleeding time in hemodialyzed patients
      receiving rHuEpo therapy. We noted a 33% decrease in Epo concentration (p < 0.05)
      after a 4-week ketanserin trial in patients in the initial stage of rHuEpo
      therapy. Although a concomitant decrease in erythrocyte count and hemoglobin did
      not reach statistical significance, these changes correlated positively with
      decreasing Epo level (r = 0.749 and 0.787, respectively). Ketanserin administered
      for 14 days to patients between 32 and 34 weeks of rHuEpo therapy also produced a
      decrease of 26% in Epo concentration (p < 0.005). This decrease correlated (r =
      0.629) with a decrement in the red blood cell (RBC) count (p < 0.005). Hemoglobin
      concentration followed the same pattern (p < 0.005). However, the decreases in
      the reticulocyte count did not reach statistical significance. The decrease in
      hormone concentration resulted in a concomitant thrombocyte decrease (p < 0.05)
      only in patients who received ketanserin in the interval between 8 and 12 weeks
      of rHuEpo therapy. The previously normal bleeding time was significantly
      prolonged (p < 0.05) in both groups of patients. There were no changes in
      leukocyte count, iron status parameters, or calcium, phosphorus, or bilirubin
      concentration. Administration of ketanserin even for 4 weeks did not influence BP
      in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8569226
TI  - Metoprolol versus sotalol in the treatment of sustained ventricular tachycardia.
AB  - The efficacy of sotalol in the treatment of sustained ventricular arrhythmias has
      been proved; however, whether its antiarrhythmic effect is due to a beta-blocking
      activity, a class III antiarrhythmic activity, or a combination of both is not
      known. We conducted a prospective randomized study to compare the effects of
      metoprolol, a "pure" beta-blocking agent, and of sotalol, a beta-blocking agent
      with additional class III antiarrhythmic properties, in 34 consecutive patients
      with documented sustained monomorphic ventricular tachycardia (VT) unrelated to
      transient causes. After undergoing baseline programmed electrical stimulation
      (PES-1) to assess arrhythmia inducibility, the patients were randomly assigned to
      a (double-blind) treatment of either metoprolol (16 patients) or sotalol (18
      patients). Before the chronic regimen was initiated, arrhythmia inducibility was
      reassessed after the intravenous administration of either 0.15 mg/kg metoprolol
      or 1.5 mg/kg sotalol (PES-2), according to drug assignment. During the chronic
      oral regimen, a third PES (PES-3) was performed after a median follow-up of 72
      days. Resting and exercise ECG, Holter monitoring and echocardiography were
      performed at baseline and during follow-up. During a 2-year follow-up, a non
      fatal arrhythmia recurred in 1 patient of the metoprolol arm and in 5 patients of
      the sotalol arm; 1 patient in the latter group died suddenly 2 months after the
      recurrence, while receiving amiodarone therapy. Intention-to-treat analysis
      showed no difference in the incidence of arrhythmia recurrence, sudden death, or
      total mortality between the two groups. During PES-1, a sustained ventricular
      arrhythmia was inducible in 18 of 34 patients (53%), 8 in the metoprolol and 10
      in the sotalol arm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8569227
TI  - Antifibrillatory effects of BRL-32872 in anesthetized Yucatan minipigs with
      regional myocardial ischemia.
AB  - The antifibrillatory potential of BRL-32872, a novel antiarrhythmic compound with
      K+ and Ca2+ channel blocking activities, was examined in a minipig model of
      ischemia-induced arrhythmia. The effects of intravenous (i.v.) BRL-32872 (0.3 and
      1.0 mg/kg, n = 8), dofetilide (0.3 mg/kg, n = 8), and flecainide (2.0 mg/kg, n =
      8), were investigated on the incidence of ventricular fibrillation (VF) during a
      20-min occlusion of the left anterior descending coronary artery (LAD). Ischemia
      induced VF occurred in 6 of 9 vehicle-treated pigs. BRL-32872 reduced the
      incidence of ischemic VF to 13% at 0.3 mg/kg (p < 0.05) and to 0% at 1.0 mg/kg (p
      < 0.01). Dofetilide also prevented the occurrence of VF (0%, p < 0.01) In
      contrast, flecainide did not reduce the incidence of VF (63%). Indeed, flecainide
      shortened the time to onset of VF from 17 +/- 1 min in the vehicle group to 10 +/
      1 min (p < 0.001). The antifibrillatory effects of BRL-32872 and dofetilide were
      associated with a prolongation of QT interval on ECG. Flecainide did not prolong
      repolarization, but slowed the ventricular conduction velocity, as shown by
      significant increases in PR and QRS intervals. During early reperfusion, 1 of 8
      surviving pigs in each group treated with BRL-32872 and 4 of 8 in the dofetilide
      group developed VF. This study demonstrated an antifibrillatory effect of BRL
      32872 associated with prolonged ventricular repolarization and showed enhanced
      efficacy over dofetilide on reperfusion arrhythmias which is most likely a
      consequence of its Ca2+ blocking activity.

PMID- 8569228
TI  - Effects of phorbol ester on vasodilation induced by endothelium-dependent or
      endothelium-independent vasodilators in the mesenteric arterial bed.
AB  - The effects of phorbol ester, phorbol 12-myristate 13-acetate (PMA), on
      vasodilation induced by endothelium-dependent or independent vasodilators in the
      mesenteric arterial bed were examined. In mesentery precontracted with
      methoxamine, acetylcholine (ACh) produced a concentration-dependent vasodilation,
      but ACh-induced vasodilation was significantly reduced when the tonus of the
      mesentery was raised by an equieffective concentration of PMA. Sodium
      nitroprusside (SNP) and forskolin also caused a concentration-dependent
      relaxation in the mesenteric arterial bed pre-contracted with methoxamine, but
      could not induce relaxation in mesentery precontracted with PMA. In mesentery
      precontracted with PMA or methoxamine, ACh-induced vasodilation was significantly
      inhibited by tetraethylammonium (TEA), but not by ouabain, glibenclamide, or
      apamin. ACh-induced vasodilation was significantly inhibited by NG-nitro-L
      arginine (L-NNA), whereas L-NNA was not capable of effectively inhibiting the ACh
      induced vasodilation of the mesentery precontracted with PMA. These results
      suggest that stimulation of protein kinase C (PKC) by phorbol ester (PMA) in the
      mesenteric arterial bed inhibits the relaxation of vascular smooth muscle (VSM)
      in response to cyclic nucleotides. Furthermore, the endothelium of the mesenteric
      arterial bed may release endothelium-derived hyperpolarizing factor (EDHF), in
      addition to nitric oxide (NO), into the mesentery.

PMID- 8569229
TI  - Effect of a calcium-sensitizing positive inotropic agent MCI-154 and its combined
      use with enalapril on postischemic contractile dysfunction of dog hearts.
AB  - We wished to elucidate the effects of the calcium-sensitizing positive inotropic
      agent MCI-154 and its combined use with an angiotensin-converting enzyme (ACE)
      inhibitor enalapril on postischemic contractile dysfunction. Anesthetized dogs
      underwent a 30-min occlusion of the left anterior descending coronary artery
      (LAD) followed by 2 h of reperfusion. Regional myocardial segment shortening in
      the ischemic LAD area was assessed by sonomicrometry. Myocardial segment
      shortening decreased in response to the LAD occlusion and remained decreased
      during 2-h reperfusion. The intravenous infusion of MCI-154 (0.1 or 0.3
      micrograms/kg/min) initiated 10 min after occlusion and throughout reperfusion
      significantly improved the recovery of segment shortening. The alleviation of the
      postischemic contractile dysfunction by MCI-154 was augmented when the animals
      were treated with a bous injection of enalapril (0.3 mg/kg) 15 min before
      ischemia followed by an infusion of the drug (0.003 mg/kg/min). The pretreatment
      with enalapril alone (0.3 mg/kg plus 0.003 mg/kg/min or 1 mg/kg plus 0.01
      mg/kg/min) did not alleviate the postichemic dysfunction, however, although it
      decreased systemic blood pressure (BP). Ischemic bed size, myocardial necrosis
      (by triphenyltetrazolium chloride staining), and collateral blood flow (by
      colored microspheres) were similar in all experimental groups. These results
      indicate that MCI-154 improves the postischemic contractile function of dog
      heart, whereas enalapril fails to improve it. ACE inhibitors may also augment the
      efficacy of cardiotonics on postischemic dysfunction.

PMID- 8569230
TI  - Is the ECG measure RSh a promising technique for detecting class I antiarrhythmic
      drug action in men?
AB  - Previous animal experiments suggest that the increase in the amplitude from the R
      wave to the S-wave (RSh) may be more sensitive than other ECG measures to sodium
      channel blocking drug actions. We measured RSh of three orthogonal leads at
      baseline and during intravenous pharmacologic stimulation with adenosine,
      ajmaline, atropine, disopyramide, isoproterenol, lidocaine, norepinephrine (NE),
      propranolol, and verapamil in an observer-blinded placebo-controlled study in
      healthy young men. The short-term reproducibility of RSh was high. Ajmaline
      increased RSh in the anteroposterior lead, disopyramide in the anteroposterior
      and vertical lead, and lidocaine in the vertical and horizontal lead,
      respectively. Isoproterenol increased RSh in the anteroposterior lead; atropine
      decreased RSh in the vertical lead. The other drugs did not affect RSh
      significantly. Our data do not support the concept that RSh measure is a more
      sensitive technique for assessing class I antiarrhythmic drug action in humans,
      at least in healthy subjects. In addition, our results indicate that changes in
      autonomic tone may influence RSh measurements.

PMID- 8569231
TI  - Carotid arterial changes produced by a centrally mediated antihypertensive agent
      in hypertensive rats.
AB  - We studied the effects of centrally mediated reduction of sympathetic outflow on
      the mechanical properties of the carotid arterial wall in spontaneously
      hypertensive rats (SHR) as compared with matched Wistar-Kyoto rats (WKY).
      Ascending aortic pressure and flow were recorded in open-chest anesthetized rats,
      and the systemic arterial compliance (SAC) was calculated. Intravenous injection
      of rilmenidine induced a transient increase in blood pressure (BP) in WKY and
      SHR, followed by a long-lasting reduction in SHR, together with a decrease in
      cardiac output (CO) and heart (HR) and a significant increase in SAC. Serial
      measurements of internal carotid artery diameter made with a newly described echo
      tracking technique showed a significant, rapid, and long-lasting constriction in
      both strains. In this set of experiments, the carotid compliance was determined
      from the arterial volume-pressure relation under control conditions and after
      administration of intravenous (i.v.) rilmenidine. In both WKY and SHR, carotid
      compliance increased, but the increase was observed only at the higher transmural
      pressure ranges and not at the operating systemic BP of the corresponding
      animals. Simultaneous recordings of the carotid arterial diameter made with the
      echo-tracking technique indicated that these compliance changes occurred in the
      presence of carotid arterial constriction at any given value of transmural
      pressure. Distensibility was increased in a higher pressure range: from 100 to
      200 mm Hg transmural pressure. The centrally mediated antihypertensive agent
      rilmenidine produced carotid arterial constriction independent of BP changes and,
      in in vivo in situ carotid preparations, arterial constriction was associated
      with a decrease in the stiffness of the arterial wall.

PMID- 8569232
TI  - Acute hemodynamic effects of ciprokiren, a novel renin inhibitor, in sodium
      depleted dogs.
AB  - We evaluated the acute hemodynamic effects of ciprokiren (Ro 44-9375), a new
      potent renin inhibitor, in sodium-depleted dogs. After dogs were sodium depleted
      by administration of furosemide, they were anesthetized, and effects of
      increasing doses of ciprokiren (0.1-3 mg/kg) or placebo on arterial blood
      pressure (BP), cardiac output (CO), coronary blood flow (CBF), left ventricular
      (LV) + dP/dtmax, and plasma renin activity (PRA) were evaluated. Ciprokiren dose
      dependently decreased arterial BP and peripheral vascular resistance (PVR),
      beginning at the 0.1-mg/kg dose and having maximal effect at 1 mg/kg. Ciprokiren
      did not change heart rate (HR), LV + dP/dtmax or coronary vascular resistance.
      Finally, a maximal effective dose of an angiotensin-converting enzyme (ACE)
      inhibitor (cilazapril 1.0 mg/kg intravenously, i.v.) had no additional
      hemodynamic effect. At 0.1 mg/kg ciprokiren, arterial BP was reduced, with no
      change in PRA, showing the dissociation between hemodynamic effects and
      inhibition of renin in plasma. Acutely, renin inhibition with ciprokiren produces
      a marked peripheral vasodilation which appears to be dissociated from the renin
      inhibition in plasma and which is not increased by additional ACE inhibition.

PMID- 8569233
TI  - Presence of aromatase inhibitors in cycads.
AB  - Cycads, the most primitive of the living gymnosperms, have been used and continue
      to be used for food and medicinal purposes by many cultures, although toxins must
      be removed before ingestion. In our quest to identify tropical plants that
      contain inhibitors of the cytochrome P-450 aromatase and thus may be efficacious
      in treating estrogen-dependent tumors, we have screened extracts from 5 species
      of cycad folia encompassing 3 genera: Cycas cairnsiana F. Muell., Cycas revoluta
      Thunb., Cycas rumphii Miq., Dioon spinulosum Dyer and Encephalartos ferox Bertol.
      All extracts were found to contain inhibitors of the human enzyme.

PMID- 8569234
TI  - Pregnancy terminating effect of Jatropha curcas in rats.
AB  - The fertility regulatory effect of the fruit of Jatropha curcas was investigated
      by oral administration of different extracts to pregnant rats for varying periods
      of time. Foetal resorption was observed with methanol, petroleum ether and
      dichloromethane extracts indicating the abortifacient properties of the fruit.
      The results also suggest that the interruption of pregnancy occurred at an early
      stage after implantation. This effect could be accomplished even when the
      extracts were given from the 6th to the 8th day of pregnancy. Loss of body weight
      during the dosing period, ranging from slight to severe was seen in the treated
      animals. Marked toxicity was observed with some extracts when given over a
      comparatively long period of about 10 days.

PMID- 8569235
TI  - Wasm: a traditional method of healing by cauterisation.
AB  - Wasm or kaii is a traditional method of healing by cauterisation. This form of
      healing, known to the Egyptians and pre-Islamic Arabs centuries ago, is still
      used in the Sultanate of Oman today. In Oman, cauterisation is performed by
      traditional healers. It is generally thought of as a special healing system which
      is used for particular diseases and on occasions when modern medicine fails to
      cure. The instrument for cauterisation is usually a metal rod, pointed at one end
      or often bent at the top into a crescent shape. Different parts of the body are
      cauterised for different ailments and diseases.

PMID- 8569236
TI  - Chronic administration of aqueous extract of Stevia rebaudiana in rats: renal
      effects.
AB  - The effects of administration of Stevia rebaudiana extracts for 20, 40 and 60
      days on renal function and mean arterial pressure in normal Wistar rats were
      evaluated. Results showed that the Stevia rebaudiana treated rats group for 20
      days did not significantly differ from the control group. Chronic administration
      of a crude extract for 40 and 60 days induced hypotension, diuresis and
      natriuresis with glomerular filtration rate (GFR) constant. An increase of the
      renal plasma flow (RPF) was exclusively observed for the group treated for 60
      days. The results suggests that oral administration to rats of an aqueous extract
      of Stevia dried leaves induce systemic and renal vasodilation, causing
      hypotension, diuresis and natriuresis.

PMID- 8569237
TI  - Immunomodulatory action of propolis. V. Anticomplementary activity of a water
      soluble derivative.
AB  - The effect of a water-soluble derivative (WSD) of propolis on the classical
      pathway (CP) and the alternative (AP) complement activity has been investigated.
      The in vitro experiments show that WSD inhibits both pathways and the effect
      depends on the source of complement. The suppression of complement-mediated
      haemolysis proves to be time- and temperature-related. High WSD concentrations
      cause direct damage of the target erythrocytes. The estimation of C3-residual
      activity indicates that the preparation diminishes C3 functional activity.

PMID- 8569238
TI  - Immunomodulatory action of propolis. VI. Influence of a water soluble derivative
      on complement activity in vivo.
AB  - The water soluble derivative (WSD) of propolis in a dose of 150 mg/kg was
      administered intravenously (i.v.), intraperitoneally (i.p.) and orally (p.o.) to
      mice. The alteration of serum alternative pathway (AP) complement level was
      observed. The WSD also influenced the process of acute inflammation provoked by
      zymosan in mice. The effect was strongly dependent on the route of WSD
      administration.

PMID- 8569239
TI  - Medical ethnobotany of the Siddis of Uttara Kannada district, Karnataka, India.
AB  - A total of 98 medicinal preparations, involving 69 species of plants, used by the
      Siddis of Uttara Kannada in the state of Karnataka is described in this paper
      based on an ethnomedical field study. The finding includes 40 hitherto unknown
      medicinal uses of known medicinal plants. Among these, the use of the stem sap of
      Calamus thwaitesii as an antifertility drug, and the use of the flowers of
      Ichnocarpus frutescens and the rhizome of Hedychium coronarium in the treatment
      of diabetes are noteworthy. The knowledge of medicinal plants of the Siddis is
      distinct from that of another tribe of the same locality, the Gowlis.

PMID- 8569240
TI  - Bioactivity of certain medicinal latexes used by the Ese'ejas.
AB  - Latexes from Croton erythrochilus, Ficus inspidia and Sapium marmieri used
      traditionally as medicinal by the Ese'ejas were analyzed for bioactivity. The
      assays run were: the brine shrimp toxicity microplate bioassay, the wheat rootlet
      growth inhibition and the DNA-methyl green bioassay. The three latexes showed
      cytotoxicity to the brine shrimp and concentration-related growth inhibition. No
      interaction with the DNA-methyl green complex was observed with any of the three
      latex samples. The field bioassays described has demonstrated to be useful for
      supporting ethnobotanical information.

PMID- 8569241
TI  - A survey of medicinal plants of Jajarkot district, Nepal.
AB  - The medicinal plants used by most of the healers or knowledgeable adults from
      local flora as remedies are discussed. Sixty species (including 2 species
      pteridophytes, 2 species monocotyledons and 56 species dicotyledons), and 25
      types of diseases have been identified in these areas through this field work. It
      seems to be appropriate to document the herbal folklore for scientific research.
      At the same time it may lend the helping hand in the conservation of plant
      biodiversity of the area as well.

PMID- 8569242
TI  - The effect of Chinese medicinal herb Zingiberis rhizoma extract on cytokine
      secretion by human peripheral blood mononuclear cells.
AB  - The ethanolic extract of the Chinese medicinal herb Zingiberis rhizoma, the
      rhizome of Zingiber officinale Roscoe (Zingiberaceae), was found to show biphasic
      effects on secretion of cytokines by human peripheral blood mononuclear cells in
      vitro. In this study, the augmentative effect of Zingiberis rhizoma extract on
      cytokine secretion was shown to be time dependent. No significant secretion of
      cytokine was noted when the reaction time was 1 or 3 h. Secretion of interleukin
      1beta (IL-1beta), interleukin-6 (IL-6), and granulocyte-macrophage colony
      stimulating factor (GM-CSF) by the mononuclear cells was markedly increased in
      the presence of a low concentration of Zingiberis rhizoma extract, varying from
      10-30 mg/ml, when the reaction time was 18 or 24 h. A higher concentration of the
      herbal extract did not show similar or stronger augmentative effect as did low
      concentration of the herbal extract.

PMID- 8569243
TI  - Biological activities of Annona glabra.
AB  - On a preliminary screening, substantial antimicrobial, antifungal and moderate
      insecticidal, sporicidal and cytotoxic activities were observed for the hexane
      extract of the stem bark of Amona glabra L. Chromatographic fractionation of this
      extract led to the isolation of kaur-16-en-19-oic acid in a large amount as the
      main constituent, which was found to be largely responsible for the biological
      activities possessed by the crude extract.

PMID- 8569244
TI  - Anti-hyperglycemic effect of some edible plants.
AB  - The anti-hyperglycemic effect of 12 edible plants was studied on 27 healthy
      rabbits, submitted weekly to subcutaneous glucose tolerance tests after gastric
      administration of water, tolbutamide or a traditional preparation of the plant.
      Tolbutamide, Cucurbita ficifolia, Phaseolus vulgaris, Opuntia streptacantha,
      Spinacea oleracea, Cucumis sativus and Cuminum cyminum decrease significantly the
      area under the glucose tolerance curve and the hyperglycemic peak. Brassica
      oleracea var. botrytis, Allium cepa and Allium sativum only decrease the
      hyperglycemic peak. The glycemic decreases caused by Psidium guajava, Brassica
      oleracea and Lactuca sativa var. romana were not significant (P > .05). The
      integration of a menu that includes the edible plants with hypoglycemic activity
      for the control and prevention of diabetes mellitus may be possible and
      recommendable.

PMID- 8569245
TI  - Saiboku-To, a herbal extract mixture, selectively inhibits 5-lipoxygenase
      activity in leukotriene synthesis in rat basophilic leukemia-1 cells.
AB  - Saiboku-To, a mixture of extracts from 10 medicinal herbs, has been used for the
      treatment of bronchial asthma in Japan. Inhibitory action of this drug on
      arachidonate 5-lipoxygenase (5-LO) metabolism in rat basophilic leukemia cells
      (RBL-1 cells) was examined. Saiboku-To significantly inhibited calcium ionophore
      stimulated synthesis of cysteinyl leukotrienes (cLTs) and leukotriene B4 (LTB4).
      Inhibition appeared 10 min after addition of the substance and reached a maximal
      value after 3 h. Saiboku-To did not inhibit the release of [3H]arachidonic acid
      (AA) from cell membrane by calcium ionophore stimulation, or the production of
      cLTs and LTB4 when LTA4-free acid was used as the substrate. However, it
      significantly inhibited the production of cLTs and LTB4 when free AA was used as
      the substrate. The production of thromboxane A2 (TXA2). a cyclooxygenase
      metabolite, was not inhibited when AA was used as the substrate in cell free
      study. These results indicate that Saiboku-To selectively inhibits 5-LO activity
      in the metabolic pathway of AA.

PMID- 8569246
TI  - In vitro screening of traditional medicines for anti-hypertensive effect based on
      inhibition of the angiotensin converting enzyme (ACE).
AB  - Traditional medicines reported to be used as anti-hypertensives or diuretics from
      different regions in the world (China, India and South America) have been
      investigated. The bioassay is based on inhibition of ACE, as measured from the
      enzymatic cleavage of the chromophore-fluorophore-labelled substrate
      dansyltriglycine into dansylglycine and diglycine. In total, 31 species have been
      investigated and the crude extracts from seven species inhibit the enzyme by more
      than 50%.

PMID- 8569247
TI  - Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with special
      reference to Centella asiatica (L.) Urban.
AB  - Centella asiatica (L.) Urban (Umbelliferae) is commonly used in the Ayurvedic
      system of medicine to treat various diseases. The present study examines the anti
      tumour effect of the crude extract (CE) of Centella asiatica as well as its
      partially purified fractions (AF) from chromatographic procedures by both in
      vitro short and long term chemosensitivity and in vivo tumour model test systems.
      AF dose dependently inhibited the proliferation of the transformed cell lines
      significantly more than did the CE and other solvent fractions. Fifty percent
      effective doses on hour 3 exposure to AF were 17 and 22 micrograms/ml for Ehrlich
      ascites tumour cells (EAC) and Dalton's lymphoma ascites tumour cells (DLA),
      respectively. However, practically no toxic effects were detected in normal human
      lymphocytes. AF also significiantly suppressed the multiplication of mouse lung
      fibroblast (L-929) cells at a concentration of 8 micrograms/ml in long term
      culture. Oral administration of the extracts (CE and AF) retarded the development
      of solid and ascites tumours and increased the life span of these tumour bearing
      mice. Tritiated thymidine, uridine and leucine incorporation assay suggest that
      the fraction acts directly on DNA synthesis.

PMID- 8569248
TI  - Anti-inflammatory activity of Vitis elongata.

PMID- 8569249
TI  - Traditional herbal medicine in Transkei.
AB  - The indigenous people of Transkei depend on natural plant resources from the
      forests for the medicinal, cultural, religious and other needs. This area,
      predominantly occupied by the Xhosa people, has remained ethnobotanically
      unexplored until recently. The present survey among the traditional doctors,
      herbalists, herb sellers, tribal priests and local people recorded medicinal uses
      of 26 plants. The firsthand information points out the significance of local
      plants to tribal groups and people of Transkei.

PMID- 8569250
TI  - Clinical analysis of Parkinson's disease treated by integration of traditional
      Chinese and western medicine.
AB  - Parkinson's discase is an extrapyramidal disease characterized by tremor,
      hypokinesis and postural reflex disturbance. It often occurs in the middle and
      the old-aged. People usually use synthetic drugs such as atropine, levodopa or
      medopa to gain temporary relief, but the side effects are serious. Along with
      prolongation of medication, the effective rate reduces step by step. Hence,
      seeking for a new therapy via the approach of integrating traditional Chinese and
      western medicine becomes a pressing issue. Since the early 1970's, the author has
      made use of Chinese herbal drugs, acupuncture and moxibustion as the main
      measures to treat this affection, and definite therapeutic effects have been
      obtained. Owing to the scarceness of data regarding syndrome differentiation and
      treatment of such illness in traditional Chinese medicine (TCM), the author puts
      forward some of her personal views in this aspect for colleagues' further
      discussion.

PMID- 8569251
TI  - Dr. Tian Naigeng's experience in treatment of albuminuria in chronic nephritis.

PMID- 8569252
TI  - Controlling cancerous pain with analgesic powder for cancers.
AB  - Analgesic powder for cancers, composed of more than 20 Chinese drugs, was applied
      externally to 91 patients with various kinds of cancers for management of
      cancerous pain. The results showed that it was remarkably effective in 42 cases,
      fairly effective in 22, effective in 22, and ineffective in 5, the total
      effective rate being 94.51%. Animal experiments indicated that the pain threshold
      was evidently higher in mice treated with this powder on the site of femoral
      artery of the hind limbs than that of the controls without application of this
      powder.

PMID- 8569253
TI  - Yishou jiangzhi (de-blood-lipid) tablets in the treatment of hyperlipemia.
AB  - The Yishoujiangzhi (de-blood-lipid) tablets (composed of Radix Polygori
      Multiflori, Rhizoma Polygonati, Fructus Lycii, Crataegus Pinnatifida and Cassia
      Tora) were used in the treatment of 130 cases of hyperlipemia, achieving an
      effective rate of 87.0% in lowering serum cholesterol and 80.8% in lowering
      triglyceride.

PMID- 8569254
TI  - Clinical observation of qingjie liyan mixture in the treatment of 46 cases of
      chronic pharyngitis.

PMID- 8569255
TI  - Treatment of migraine with modified chuanxiong powder--a report of 30 cases.

PMID- 8569256
TI  - Treatment of biliary colic by water injection in the region of Qimen, Riyue, and
      Juque points.
AB  - Water injection was used in the treatment of 56 cases of biliary colic. The
      method was based on the writings of Zhang Zhongjing about the role of the Qimen
      point in treating diseases and clinical practice in this respect, water injection
      being performed at the most sensitive spot in the region defined by the lines
      joining the Qimen (Liv 14), Riyue (GB 24), and Juque (Ren 14) points. Pain
      disappeared in 32 (57.1%) of the 56 cases treated, and the total effective rate
      was 96.4%, showing a significantly better result compared with that of the
      control group treated with Western medicine (P < 0.05).

PMID- 8569257
TI  - Treatment of cancerous abdominal pain by acupuncture on zusanli (ST 36)--a report
      of 92 cases.

PMID- 8569258
TI  - 23 cases of summer fever treated by needling huatuojiaji points.

PMID- 8569259
TI  - An exploration of eight-liao points.

PMID- 8569261
TI  - Personal experience with acupuncture therapy.

PMID- 8569260
TI  - Dr. Zhou Chaofan's experience in the treatment of migraine.

PMID- 8569262
TI  - Anti-inflammatory effects of tianrong acupoint on blood vessels of dura mater.
AB  - Although Tianrong acupoint (SI 17) is used for migraine headache, its mechanism
      of action remains obscure. The effects of Tianrong acupoint therapy on
      neurogenically-mediated plasma protein extravasation (125I-BSA) in rat dura mater
      induced by electrical stimulation of the right trigeminal ganglion was studied.
      When the unilateral trigeminal ganglion was stimulated (5 Hz, 1.2 mA, 5 msec for
      5 min), the ratio of stimulated side/unstimulated side (cpm/mg) was 1.6663 +/-
      0.0217. The plasma extravasation was blocked by different kinds of treatment in
      different degrees. The order of the ratio was as follow: Tianrong acupoint
      therapy (1.0917 +/- 0.0266) and Tianrong electrical needle therapy (1.1281 +/-
      0.0227) < Tianrong acupoint injection with normal saline (1.325 +/- 0.0444) <
      Quchi acupoint (LI 11) injection with prednisolonum (1.5284 +/- 1.1624). The
      results indicated that Tianrong acupoint therapy could inhibit the neurongenic
      inflammation on the affected side.

PMID- 8569263
TI  - Application of xiang cheng san in treatment of chronic protracted diarrhea in
      children.
AB  - One hundred and sixty-two children suffering from chronic protracted diarrhea
      were randomly divided into two groups and observed clinically. In the Chinese
      herbal medicine group (HM group), Xiang Cheng San was externally applied to the
      umbilicus of patients, while in the western medicine group (WM group), western
      drugs were routinely given. The results showed that the therapeutic effects were
      markedly better in the HM than in the WM group. Animal experiments showed that
      external application of Xiang Cheng San may inhibit hyperperistalsis of the
      intestine in mice, suppress peristalsis of the isolated smooth muscles in
      rabbits, and dilate micro-vessels and thus improve micro-circulation of the
      mesentery in rats.

PMID- 8569264
TI  - A train of thought for delay of senility.

PMID- 8569265
TI  - Recent progress in the studies on weight reduction by acupuncture and
      moxibustion.

PMID- 8569266
TI  - Treatment of ulcerative colitis with acupuncture.

PMID- 8569267
TI  - The external modalities for treatment of vascular hypertension.

PMID- 8569268
TI  - Acupuncture treatment of epigastric pain.

PMID- 8569269
TI  - Surgical treatment for carcinoma of the gallbladder.
AB  - Carcinoma of the gallbladder has always been associated with dismal prognosis. In
      this study we present single institution experience in surgical treatment for
      gallbladder cancer obtained during last five years. Even with recent improvement
      in diagnostic imaging modalities gallbladder malignancies are still diagnosed too
      late. The choice of operative procedure for a treatment of gallbladder carcinoma
      still remained the open question. Carcinoma of the gallbladder is not very common
      disease in Europe, but some how more common in Poland. According to the National
      Register, based on a study from 1991, 1863 cases of death from the gallbladder
      carcinomas were registered [13]. At the same time 2015 new cancer cases were
      diagnosed and registered. These gave us a crude rate of new cases in 1991 as
      follows: 2.7/100,000 man and 7.7/100,000 female. Those were even higher for some
      voivodeships in 1988, for example: Lodz (M = 3.95/100,000, F = 10.58/100,000) and
      Warsaw (M = 3.15/100,000, F = 7.59/100,000). Carcinoma of the gallbladder has
      always been associated with dismal prognosis. This was essentially the result of
      the slow and asymptomatic growth of the neoplasm that infiltrates the surrounding
      structures, such as the portal vein, hepatic artery and liver parenchyma, making
      a curative surgical treatment almost impossible. So there is a general impression
      that no progress has been made during last 20 years in the treatment for
      carcinoma of the gallbladder [2, 7, 9, 12]. However, in last years, we have
      observed improvements in diagnostic, surgical and intensive care techniques that
      allowed to offer a wider range of surgical and non-surgical options to our
      patients [1, 3, 4, 6, 8].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8569270
TI  - Zinc and magnesium serum levels in patients with benign prostatic hyperplasia
      (BPH) before and after prazosin therapy.
AB  - In 32 patients with benign prostatic hyperplasia (BPH) serum levels of zinc and
      magnesium were studied before and after prazosin therapy with (Minipress-Pfizer),
      4 mg daily. Following cessation of therapy a slight increase in Zn levels was
      observed, i.e. from 99.79 to 103.29 micrograms/dl, whereas Mg levels did not
      change significantly (1.95 and 1.94 mg/dl, respectively). In comparison with
      other organs, the human prostate is characterized by high Zn and Mg content. In
      BPH the Zn levels are increased. They are markedly decreased in carcinoma of the
      prostate and in prostatitis [4, 5]. Zn and Mg play an important role as catalysts
      in various enzymatic reactions. It has been postulated that changes in
      concentrations of these two elements are parallel [6]. Kvist has found that Zn
      imparts resistance to detergent-induced decondensation of spermatozoon nuclear
      chromatin. The effect was more pronounced with higher Zn concentrations in a
      buffer fluid. Other bivalent cations were found to be ineffective in stabilizing
      nuclear chromatin under such conditions. A possible role for seminal zinc in
      prevention of the reduction of disulfide cross-links and nuclear decondensation
      was postulated [2]. Zinc also plays an important role in protein synthesis. Zinc
      ions inhibit androgen metabolism in the prostate. Physiologic Zn serum levels are
      equal to or above 90 micrograms/dl [4, 6]. Magnesium, unlike zinc, is uniformly
      distributed within different areas of the gland. In BPH, both normal and
      increased Mg levels in the prostate have been reported [6]. Mg plays an important
      role as an activator of enzymes (phosphatases) involved in ATP metabolism, thus
      affecting both katabolic and anabolic processes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8569271
TI  - Does combined single intravenous injection of doxorubicin and verapamil have any
      influence on hemodynamic parameters in rabbits?
AB  - The hemodynamic effects of a single intravenous injection of doxorubicin (DXR) in
      a dose of 3 mg/kg, verapamil (Vp) in a dose of 0.2 mg/kg and combined
      administration of the same doses of both drugs in rabbits were investigated.
      Cardiac output (CO), stroke volume (SV), heart rate (HR), mean arterial pressure
      (MAP) and total peripheral resistance (TPR) were estimated before and repeated in
      the 1st, 15th, 30th, 45th, 60th, 90th and 120th minute after injection of the
      drugs. It was found that administration of Vp after DXR or DXR after Vp produced
      significant decrease of MAP. However, no significant changes of CO, SV, HR and
      TPR in rabbits treated with DXR and Vp were noted. Rhythm disturbances occurred
      in animals receiving DXR or DXR with Vp. The obtained results indicate the need
      for further experimental studies before the introduction of combined treatment
      with DXR and Vp to cancer patients.

PMID- 8569272
TI  - Preoperative assessment of myometrial invasion of endometrial carcinoma by
      transvaginal ultrasonography.
AB  - Preoperative transvaginal ultrasonographic evaluation of myometrial invasion was
      performed in 33 patients with endometrial cancer and compared with histologic
      findings. TVU was remarkably precise in predicting deep myometrial invasion
      (accuracy 91.7%) but superficial myometrial invasion (sensitivity 20%). TVU was
      highly accurate in patients with tumours limited to the endometrium (sensitivity
      100%) and the sensitivity of TVU in distinguishing nil or superficial versus deep
      invasion was 87.8%. TVU appears to be an efficient, economic, and practical tool
      for this purpose, however its limitation leads to more complex imaging
      techniques, especially in patients in whom preoperative irradiation or
      conservative management is planned.

PMID- 8569273
TI  - The Rett syndrome. A case report.
AB  - A rare case of a 40 month old girl has been diagnosed clinically to be that of
      the Rett syndrome, i.e. demonstrating regression in the development, repetitive
      handwringing movements and inability to speak. There were no specific laboratory
      findings.

PMID- 8569274
TI  - Benign prostatic hyperplasia. Current strategy and pharmacotherapeutical
      potential.

PMID- 8569275
TI  - The activity of glucose-6-phosphate dehydroxygenase and glutathione enzymes in
      red blood cells in patients with haemoblastoses.
AB  - The activity of glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase
      (GSSG-R), glutathione peroxidase (GSH-Px) and MDA levels have been assayed in red
      blood cells (RBC), obtained from 57 people suffering from haemoblastoses. The
      activities of G6PD in the RBC in patients with polycythemia vera (PV) and chronic
      lymphoid leukemia (CML) are significantly higher than those in healthy patients.
      Changes in the activity of glutathione dependent enzymes GSSG-R and those of GSH
      Px in the RBC go in opposite directions: the activity of GSSG-R is significantly
      enhanced in patients with PV and CML, but the activity of GSH-Px is decreased in
      all patients suffering from haemoblastoses. The high levels of MDA in the RBC of
      all patients with haemoblastoses indicate intensification of lipid peroxidation
      in their RBC.

PMID- 8569276
TI  - Differential effects of gonadectomy on thymic stromal cells in promoting T cell
      differentiation in mice.
AB  - Twenty-six week-old BDF1 mice were gonadectomized and grafted with thymus from
      irradiated (8.5 Gy) newborn, 6-week-old, or 26-week-old mice. One month later,
      grafted thymuses were recovered and examined in terms of thymocyte numbers,
      subpopulations and proliferative responses to Concananavlin A (Con A). The growth
      of the irradiated thymus was significantly higher in gonadectomized (Gx) than in
      sham-operated (Sham) mice and the magnitude of thymic growth was apparently age
      dependent, as it was greater for newborns than for older mice. Con A response of
      thymocytes was also significantly higher in Gx mice than in Sham mice, and the
      magnitude of the response declined with advancing age of the thymus donors. Flow
      cytometric analysis revealed that a significant increase in the percentage of
      CD4+CD8- was observed in thymus grafts showing high Con A responses. However,
      this effect of Gx on the thymus graft was dependent on age of the thymus donor.
      Namely, newborn thymus grafts could grow equally well in both Gx and Sham
      recipients, whereas thymus grafts from 6- and 26-week-old mice could grow well
      only in Gx, but not in Sham recipients. The number of thymocytes was comparable
      in thymus grafts from 6- and 26-week-old mice, but the proliferative response to
      Con A was higher in the former than in the latter graft. Collectively, Gx
      appeared to promote immigration of thymocyte precursors into the thymus and to
      enhance proliferation and differentiation of thymocytes towards CD4+CD8- T cells,
      in an age-related manner.

PMID- 8569277
TI  - Age-related increase in peptidylarginine deiminase in the male rat pituitary.
AB  - We have measured the activity of peptidylarginine deiminase (EC 3.5.3.15) in male
      Wistar rat pituitaries at various ages. Pituitaries obtained from 3- and 9-month
      old rats showed negligible activities. The mean enzyme activity increased
      appreciably by 18 months and markedly by 24 months accompanied with actual
      increases in the enzyme content. The peptidylarginine deiminase mRNA content
      showed a similar but more gradual increase appreciable from 9 months. Many enzyme
      positive cells were present in the pars distalis of 24-month-old male
      pituitaries. Most of the enzyme-positive cells coincided with lactotrophs. The
      pituitary prolactin content showed a gradually increasing profile resembling that
      of the enzyme mRNA, but the serum prolactin concentration did not increase
      significantly. Neither the serum 17 beta-estradiol content nor the pituitary
      estrogen receptor content showed significant variation that could account for the
      marked increase in the pituitary enzyme content between 18 and 24 months of age.
      These data suggest possible presence of other factors regulating the enzyme
      content in old male pituitaries.

PMID- 8569278
TI  - Increasing multiple myeloma mortality rates in the elderly: demonstration of
      increasing dependency with increasing age upon age group population size.
AB  - Multiple myeloma mortality rates in the elderly are increasing. Using published
      United States mortality data, annual age-specific multiple myeloma mortality
      rates from 1968 to 1989 were determined for age groups over age 60 and compared
      to corresponding annual age group population sizes. Rising multiple myeloma
      mortality rates among the elderly in the United States from 1968 to 1989 were
      increasingly dependent, with increasing age, upon increasing age group population
      size. This finding suggests that differential survival, and its effect upon the
      surviving gene pool in an aging population, may account for observed increasing
      multiple myeloma mortality rates in recent successive elderly cohorts. A similar
      conclusion regarding increasing multiple myeloma mortality rates in the elderly
      has been derived using the Strehler-Mildvan modification of the Gompertz
      relationship.

PMID- 8569279
TI  - Enhanced expression of cyclin D1 in senescent human fibroblasts.
AB  - When human fibroblast, TIG-1, was growth-stimulated with fetal bovine serum, the
      induction level of cell cycle-dependent genes was generally much lower in
      senescent cells than in young counterparts. Exceptionally, the expression level
      of cyclin D1 in senescent cells was constitutively higher than in young cells and
      further increased after serum stimulation, which was confirmed by Northern and
      Western blots and immunoprecipitation. This was also true in other human diploid
      fibroblast lines, TIG-3 and MRC-5. However, cyclin D1-dependent kinase activity
      was not detected in senescent cells. When sense- or antisense-cyclin D1 cDNA
      driven by beta-actin promoter was transfected into young TIG-1 cells, the number
      of appeared colonies from sense-strand transfected cultures was lower than that
      from antisense-strand-transfected ones. However, clones expressing cyclin D1 at
      low or undetectable level which were isolated after transfection with antisense
      cyclin D1 proliferated up to the same division limit as untransfected and sense
      strand transfected cells. Four clones of SV40-transformed TIG-1 expressed cyclin
      D1 at moderate levels during their extended proliferative lifespan. It appears
      that, if the extremely overexpressed cyclin D1 could cause an inhibition of cell
      proliferation at senescent stage, cellular senescence occurs regardless of
      overexpression of cyclin D1.

PMID- 8569280
TI  - Relevance of oxidative stress to the limited replicative capacity of cultured
      human diploid cells: the limit of cumulative population doublings increases under
      low concentrations of oxygen and decreases in response to aminotriazole.
AB  - Human diploid cells, TIG-7, were serially cultivated under 1%, 5% or 21% (air)
      oxygen. The limit of their cumulative population doublings was extended by 16% or
      10% under 1% or 5% oxygen, respectively, as compared with that under 21% oxygen.
      When TIG-7 cells were serially cultivated in the presence of 10 mM or 20 mM 3
      amino-1H-1,2,4-triazole, an inhibitor of catalase scavenging hydrogen peroxide,
      the limit of their cumulative population doublings was shortened by 4.4% or
      14.4%, respectively, as compared with untreated cells. In addition, long-term,
      rather than short-term, exposure of TIG-7 cells to aminotriazole retarded cell
      growth. Treatment with aminotriazole caused decreases not only in catalase
      activity but also in superoxide dismutase activity and reduced glutathione
      concentration, and an increase in glutathione peroxidase activity. These results
      suggest that the limit of the cumulative population doublings of human diploid
      cells is extended or shortened under decreasing or increasing oxidative stress,
      respectively. Oxidative stress may be relevant to replicative capacity, and a
      causative factor for oxidative stress may be hydrogen peroxide.

PMID- 8569281
TI  - Age-related changes in the uptake and release of glutamate and aspartate in the
      mouse brain.
AB  - The studies were carried out on 3- and 7-day, 3-, 6-, 12-, 18- and 24-month-old
      mice. The levels of glutamate and aspartate increased in most brain areas in
      developing mice and then decreased gradually during ageing, the changes
      depending, however, on the brain region. The maximal velocity (V) of high
      affinity uptake of [3H]glutamate was markedly reduced in cerebral cortical
      synaptosomes at the age of 24 months, indicating an age-related loss in the
      number of transport sites. The transport constant (Km) was also diminished in
      aged mice, indicating a compensatory increase in the affinity of the remaining
      transport sites. The basal and K(+)-stimulated (50 mM) release of endogenous
      glutamate and aspartate varied depending on the brain region. The responses to K+
      stimulation generally increased during maturation, whereas the other age-related
      changes were more variable. The basal unstimulated release of glutamate remained
      fairly constant in the cerebral cortex during ageing, but K+ depolarization
      liberated more glutamate in 24-month-olds than in 3-month-olds. The decreased
      uptake capacity together with an increased release of glutamate may contribute to
      the degenerative changes associated with normal brain ageing and also to the
      pathogenesis of age-related neurodegenerative disorders.

PMID- 8569282
TI  - Decreases in protective enzymes correlates with increased oxidative damage in the
      aging mouse brain.
AB  - We used several biochemical assays to evaluate age-related changes in antioxidant
      enzyme levels vs. free-radical damage in the murine brain. We found levels of
      several free-radical scavenging enzymes in the brains of 24-month-old C57B1 male
      mice vs. 12-month-old animals were decreased, including superoxide dismutase
      (SOD), catalase, and glutathione reductase (GSSG-Rd). In addition, we found
      concomitant increases in the levels of several forms of free-radical damage
      including sensitivity to lipid peroxidation as measured by the thiobarbituric
      acid test, protein oxidation as measured by glutamine synthetase (Gln Syn)
      activity, as well as increases in oxidized glutathione (GSSG) levels, a measure
      of oxidative stress. These data suggest that decreases in levels of enzymes which
      ordinarily protect neuronal cells against oxidative stress with age may be
      responsible for increased levels of free-radical damage in the murine brain, or
      that these enzymes themselves are susceptible to inactivation by free radical
      molecules which increase with age in the brain.

PMID- 8569283
TI  - Age-dependent stimulation or inhibition of calcium release from bone cultures by
      interleukin-1 beta.
AB  - Previous studies have shown that interleukin-1 beta (IL-1 beta) is a potent bone
      resorption stimulating agent in cultures of fetal or neonatal bones. In the
      present study, evidence has been provided showing that this cytokine failed to
      stimulate bone resorption in cultured 75-day-old mouse calvaria maintained in a
      chemically defined medium for 14 days, as determined by measuring calcium release
      into the medium and histological examination of cultured bones. Moreover, the
      cytokine significantly inhibited basal bone resorption in cultured 75-day-old
      mouse calvaria, a finding reminiscent of the paradoxical effect observed with 1
      alpha,25-dihydroxycholecalciferol. Since IL-1 beta did not alter the number of
      osteoclasts present in the cultured older calvaria as compared to the untreated
      control, we hypothesized that in such cultured older bones the cytokine affects
      primarily the function rather than proliferation/differentiation of osteoclasts,
      either directly or indirectly through its action on other cells in bone tissue,
      such as osteoblasts or stromal cells. Also, it is possible that the cytokine
      affects the formation and/or function of macrophages that have been shown to
      participate in the bone resorption process. These findings support the concept
      that at different stages of host maturation, bone tissue may exhibit a different
      response to the same osteotropic agent.

PMID- 8569284
TI  - Decreased capacity of aged mice to produce interferon-gamma in Legionella
      pneumophila infection.
AB  - We investigated the difference in natural resistance to Legionella pneumophila
      infection between aged (18-20-month-old) and young (3-month-old) mice of ddY
      strain. Aged mice were more susceptible to the bacterial infection than young
      mice; 50% lethal doses of L. pneumophila for aged and young mice were 2.2 x 10(7)
      and 8.5 x 10(7) colony forming units (CFU), respectively, after intraperitoneal
      injection of the bacteria. The bacterial burden in the livers was larger in aged
      than young mice after a challenge with a sublethal dose of L. pneumophila.
      However, peritoneal macrophages of aged mice paradoxically had a greater capacity
      to kill intracellular L. pneumophila than those of young mice. Interferon-gamma
      (IFN-gamma) production from naive spleen cells was compared after an in vitro
      stimulation with formalin-killed L. pneumophila. Spleen cells of aged mice
      produced significantly less IFN-gamma than those of young mice. When anti-murine
      IFN-gamma monoclonal antibody was administered before the bacterial infection,
      the subsequent bacterial burden in the livers significantly increased in young
      but not in aged mice. These data suggest that, in aged mice, IFN-gamma production
      is depressed at an early phase of L. pneumophila infection and it renders aged
      mice more susceptible to the infection.

PMID- 8569285
TI  - Age-associated changes in mitogen-induced lymphoproliferation and lymphokine
      production in the long-lived brown-Norway rat: effect of caloric restriction.
AB  - We have previously demonstrated that age-related declines in Concanavalin A
      (ConA), induced proliferation and lymphokine production, occur in ad-libitum fed
      Brown Norway (AL BN) rats. Since caloric restriction (CR) extends lifespan, we
      expected that the age related changes in immune parameters would be delayed by
      CR. CR does act to delay age-related changes in proliferation in response to
      ConA. In addition, CR postpones the plateau in ConA induced interferon (IFN)
      production seen after 23 months of age in AL rats. However, CR does not postpone
      the age-related decline in ConA induced interleukin-2 (IL-2) production.
      Therefore, ConA induced IFN production maybe a good candidate as an early marker
      of physiologic aging, while ConA induced proliferative response is a possible
      candidate for a marker of late stages of aging.

PMID- 8569286
TI  - Postnatal development of methionine-enkephalin modulation of cholinergic
      transmission in cat ileum.
AB  - The age-dependent effects of methionine-enkephalin (Met-enk) on contractions and
      [3H]-acetylcholine ([3H]-ACh) release evoked by electrical field stimulation
      (EFS) were studied in vitro on cat terminal ileum of young (2-month old) and
      adult cats. Radioactivity was measured by liquid scintillation spectrometry and
      the effect of Met-enk was evaluated by the FrS2/FrS1 ratio. Scopolamine, 1
      microM, abolished the EFS-induced contractions. Met-enk dose dependently (0.01-1
      microM) decreased the EFS-induced contractions. The inhibitory effect of Met-enk
      on the evoked contractions was more pronounced in adult cats compared to that in
      young cats. In adult animals Met-enk, 1 microM, almost completely inhibited the
      evoked contractions (94.6 +/- 2.6% of inhibition) while in the young cats its
      inhibitory effect was less pronounced (52.1 +/- 6.8%). Met-enk decreased the EFS
      evoked release of [3H]-ACh by 44.6 +/- 4.6% in adult cats and by 21.6 +/- 1.6% in
      young cats. The data suggest opioid modulation of cholinergic transmission in cat
      terminal ileum at neuronal level occurring as early as the postnatal period and
      increasing with the ontogenesis.

PMID- 8569287
TI  - A mortality kinetics approach to characterizing the fractionated exposure
      mortality response relationship of radon progeny.
AB  - The utility of mortality kinetics analysis in evaluating mortality data from
      fractionated exposure studies was demonstrated using radon-progeny induced extra
      mortality as an example. Gompertz (log-hazard) functions were used to
      characterize the mortality of male SPF Wistar rats exposed to radon progeny at
      100 WL and 1000 WL for total exposures ranging from 20 to 10,240 WLM. There was
      an upward parallel displacement of the Gompertz functions following the period of
      radon exposure. The shape of the Gompertz functions for the exposed animals was
      consistent with a Gompertz model of toxicity resulting from short-term exposure,
      resulting in non-repaired injury that summates with natural (aging) injury. The
      parallel upward displacements (epsilon ss) of the Gompertz functions showed an
      unexpected non-monotonic pattern for rats exposed at 1000 WL. The parallel upward
      displacements showed a sharp upward increase from 320 to 640 WLM, fell at 1280
      WLM, and thereafter increased linearly to 10,240 WLM. These data suggest that the
      radon progeny exposure-mortality response is non-linear. In contrast, there was
      no significant parallel upward displacement of the Gompertz functions for rats
      exposed at 100 WL for total exposures of 20-1280 WLM, but a large displacement
      began at 2560 WLM total exposure.

PMID- 8569288
TI  - On age-related changes of cell membrane permeability in human buccal epithelium
      cells.
AB  - An original method for the determination of cell membrane permeability has been
      developed. Human buccal epithelium cells were treated with Indigo Carmine and the
      percentage of stained cells was determined. Employing this method, the age
      related differences in properties of plasma membrane in cells of human buccal
      epithelium were demonstrated. In the group of aged donors the average level of
      cell stainability was higher than in the group of younger donors. These results
      demonstrate a decrease in outer cell membrane integrity with age.

PMID- 8569289
TI  - High levels of mitochondrial DNA deletions in skeletal muscle of old rhesus
      monkeys.
AB  - Mitochondrial DNA (mtDNA) deletions increase in abundance with age in many
      tissues, however, their calculated low levels (usually < 0.1%) in samples from
      tissue homogenates containing thousands of cells argue against physiologic
      significance. Through the analysis of defined numbers of cells (skeletal muscle
      fibers) from rhesus monkeys, we report that the calculated abundance of specific
      mtDNA deletions is dependent upon the number of fibers analyzed: as the number of
      fibers decreases, the calculated deletion abundance increases. Also, most mtDNA
      deletions appear to occur in a mosaic pattern, varying from cell to cell in size,
      number and abundance. These data support the hypothesis that mtDNA deletions can
      focally accumulate to high levels contributing to declines in mass and function
      of aging skeletal muscle.

PMID- 8569290
TI  - Principles of cancer screening.
AB  - Screening for cancer is an important aspect of cancer prevention and treatment.
      The science of screening is based on epidemiologic principles that are central to
      understanding the potential risks and benefits of a screening program. Screening
      is best applied to those conditions that are relatively common and have an
      important impact on quality of life and for which acceptable tests and treatments
      are available and affordable.

PMID- 8569291
TI  - Barriers to cancer screening.
AB  - Many barriers to cancer screening have been summarized and discussed. Barriers
      have been documented in all patient populations, but some groups such as ethnic
      minorities and the elderly face unique barriers. The barriers to cancer
      screening, are multifactorial, but much of the responsibility for change must lie
      with health care providers and the health care delivery industry. This is not to
      free the patient of all responsibility, but some significant barriers are beyond
      their direct control. Take, for example, socioeconomic status, disease knowledge,
      and culturally related perceptions and myths about cancer detection and
      treatment. The health care industry must do a better job identifying and
      overcoming these barriers. The significant effects of provider counseling and
      advice must not be underestimated. Patients must first be advised, and then
      further actions must be taken if they reject the screening advice. Did they
      refuse adherence to recommendations because they do not view themselves as
      susceptible, because of overwhelming personal barriers, or because of a
      fatalistic attitude toward cancer detection and treatment? If that is the case,
      physicians and health care institutions must attempt to change perceptions,
      educate, and personalize the message so that patients accept their disease
      susceptibility [table: see text]. Multiple patient and provider risk factors have
      been identified that can be used to target patients particularly at high risk for
      inadequate cancer screening and providers at high risk for performing inadequate
      screening. Research has clearly demonstrated the effectiveness of interventions
      to improve tracking of patient and physician compliance with screening
      recommendations. Further research is needed to show the impact of managed-care
      penetration and payer status on screening efforts, and incentive schemes need to
      be tested that reward institutions and third-party payers who develop uniform
      standards and procedures for cancer screening. The greatest responsibility lies
      with medical and health care institutions and those who determine the priorities
      of these institutions. Patient and physician barriers to mass cancer screening
      can be addressed by institutional support. If the quality of care delivered by
      providers, group practices, managed-care organizations, and HMOs is assessed with
      priority given to the regularity and consistency with which basic screening
      procedures are performed, cancer screening will undoubtedly receive greater
      attention in the clinic. Medical institutions must collaborate to develop
      standards for cancer screening with attention to the cost-effectiveness of
      various screening techniques to determine how limited resources can best be spent
      in cancer control. Such efforts should keep in mind "that a very small change
      implemented over a broad population may have a greater effect in absolute numbers
      than a large level of change applied in a small segment of the population."

PMID- 8569293
TI  - The disclosure of the diagnosis of cancer.
AB  - Before significant efforts relative to patient education and subsequent informed
      decision making can occur, it is essential to assess the patient's perceptions
      and emotional responses to the diagnosis. The direction and depth of this
      exploration are likely to be determined by such factors as quality of the
      previous relationship with the patient, the patient's belief and support system,
      and the patient's previous experience with trauma. Other determining factors are
      the sense of urgency with which medical decisions need to be made and the
      interpersonal skills of the physician. It is important at the time of diagnosis
      to understand and respond to the patient's cognitive and emotional responses to
      the diagnosis. The sensitive physician allows time to acknowledge and legitimate
      those responses. It is often important to allow the ventilation of those
      reactions before further education and decision making can occur. By accepting
      and acknowledging the patient's reactions, the physician can reduce the patient's
      feelings of isolation and helplessness. The quality of such a relationship then
      becomes the foundation on which the patient and family and physician can begin to
      attend to the issues before them.

PMID- 8569292
TI  - The role of midlevel providers in cancer screening.
AB  - Data indicate that midlevel providers are more likely to provide health promotion
      and disease prevention counseling, health education, and preventive health and
      screening services as well as use more community resources. Although the
      literature is sparse regarding cancer screening activities by midlevel providers,
      such activities are routinely taught in midlevel educational programs, and
      midlevel providers see these activities as consistent with their roles.
      Therefore, it is only logical to assume that use of midlevel providers, who have
      already been shown to focus on health promotion and disease prevention, would be
      an effective way to provide quality, cost-effective cancer screening. In fact,
      models of this sort exist around the United States at the present time, such as
      the one at Moffitt Cancer Center's Lifetime Cancer Screening Program in Tampa,
      Florida. In such programs, midlevel providers are successfully conducting
      comprehensive cancer screening activities. Outcome data from these programs have
      yet to be published, however. In a collaborative practice environment, the
      delivery of preventive care, including cancer screening activities, is best
      accomplished when both the physician and the midlevel provider agree on the
      importance of these screening activities and work together as a team to integrate
      these preventive health activities into their office practice. Office systems
      that are sensitive to patient preferences and that promote preventive care, such
      as protocols and checklists or health maintenance flowsheets, along with
      appropriate education tailored to patients' ages and to their social, cultural,
      and educational backgrounds also help to improve compliance with cancer screening
      guidelines. More than ever before, health care reform has been the focus of
      national debate. Most of the health care reform proposals that have been advanced
      recognize the importance of primary and preventive health care and the role that
      midlevel providers could and should be playing in such a system. As competent
      providers, NPs, CNMs, and PAs have the ability to enhance medicine's
      effectiveness in preventive care, through improved outreach and more thorough
      screening.

PMID- 8569294
TI  - Breast cancer screening and compliance and evaluation of lesions.
AB  - It appears that screening mammography certainly is of value in women over age 50,
      and although controversy exists regarding screening of women under 50 years of
      age for breast cancer, the authors believe that this strategy is the most
      reasonable one for women 40 to 64 years of age at this time. Additionally, it is
      important for physicians to remember to encourage their patients to undergo
      cancer screening evaluation. Encouragement by physicians is an important factor
      in increasing cancer screening rates.

PMID- 8569295
TI  - Metastases of unknown primary site.
AB  - Despite the fact that effective therapy does not currently exist for the majority
      of patients presenting with metastases of unknown primary site, the last decade
      has witnessed significant advances in the approach to this heterogeneous disease.
      The use of modern pathologic techniques that frequently provide better diagnostic
      precision and the recognition of specific subgroups with a favorable prognosis
      and responsiveness to treatment has improved the outcome for some patients.
      Currently the diagnostic strategy should emphasize the rapid identification of
      patients likely to benefit from available therapy, whereas clinical research
      should focus on the development of more effective treatments for those patients
      with unresponsive tumors. In the future, continued improvements in the molecular
      characterization of these tumors will likely enhance understanding of the
      metastatic process, allow for more specific definitions of cell lineage, and
      provide insights for better therapy.

PMID- 8569296
TI  - Paraneoplastic syndromes.
AB  - The paraneoplastic syndromes are effects of cancer that occur at sites remote
      from the primary tumor and its metastases. Recognition of these disorders is
      important from both diagnostic and therapeutic viewpoints. The important
      paraneoplastic syndromes involving the endocrine, nervous, hematologic, and
      dermatologic systems are discussed in this article.

PMID- 8569297
TI  - Tumor markers. An update.
AB  - Cancer remains the second leading cause of death in developed countries, and the
      incidence of certain tumors is increasing despite emphasis on prevention and
      screening. Tumor markers are biologic or biochemical substances that are produced
      by tumor cells and then secreted into the circulation in detectable amounts. This
      article covers some of the more common tumor markers currently being utilized for
      diagnostic and prognostic purposes.

PMID- 8569298
TI  - Radiologic imaging in cancer.
AB  - Radiologic procedures are extremely valuable in the diagnostic work-up of many
      cancers but are limited for screening purposes to a few diseases. Radiologists
      have developed an extensive armamentarium of tools, from plain radiographs and
      nuclear-medicine scans to ultrasound, computed tomography, magnetic resonance
      imaging, positron emission tomography, and single-photon emission computed
      tomography. This article includes suggested protocols for working up the most
      common cancers.

PMID- 8569299
TI  - Colorectal cancer screening.
AB  - The decision whether to launch a screening program in asymptomatic patients of
      average risk for colorectal cancer and the selection of the appropriate protocol
      for screening are complex issues. There are still many unanswered questions. Many
      organizations such as the American Cancer Society, the World Health Organization
      Collaborating Center for the Prevention of Colorectal Cancer, and the U.S.
      National Cancer Institute advocate screening with annual Hemoccult tests and
      screening with flexible sigmoidoscopy every 3 to 5 years in patients more than 50
      years of age. The U.S. Preventive Services Task Force, the Canadian Task Force on
      Periodic Health Examination, and the International Union Against Cancer have not
      recommended screening asymptomatic average-risk patients for colorectal cancer.
      One study showed a small but significant benefit (3 per 1000) of the rehydrated
      annual Hemoccult test in reducing mortality from colorectal cancer. To embark on
      a mass screening strategy as recommended, however, would require significant
      costs, increases in physician training, improved access to the requisite
      technology, and enhancements in patient and physician compliance. Furthermore,
      the high false-positive rates of the rehydrated Hemoccult tests would lead to
      many unnecessary tests, causing greater expense as well as patient discomfort and
      anxiety. It is, therefore, premature to recommend mass screening for colorectal
      cancer in asymptomatic individuals at this time. Further research is needed to
      identify risk factors (such as genetic markers) better and to develop and
      evaluate screening strategies targeted at those with high risk for colorectal
      cancer. In the meantime, efforts at primary prevention for the general population
      should be increased (through nutrition and exercise). Patients over the age of 50
      who desire screening should be given information of the benefits and risks of
      screening and together with their physicians decide on a screening strategy that
      suits their needs and values.

PMID- 8569300
TI  - Screening and early diagnosis of gynecologic cancers.
AB  - Gynecologic malignancies remain an important health concern for women. The
      primary care practitioner plays a valuable role in performing regular Pap smears
      and pelvic examinations. Although routine screening for asymptomatic women for
      ovarian and endometrial cancer cannot be recommended at this time, vaginal
      ultrasound is a valuable tool for the evaluation of postmenopausal bleeding and
      ovarian masses.

PMID- 8569301
TI  - Early detection in lung cancer. Case finding and screening.
AB  - There is general agreement that the most effective approach to lung cancer is
      primary prevention--stop smoking. Richards has proposed the MVROCST--the
      Monosyllabic Verbal Response Office Cancer Screening Test: "Do you smoke?" If
      "yes," intervene. If "no," move on. Ample evidence exists that a clear message
      from a physician to a patient about the importance of stopping smoking makes a
      difference. In contrast to the maze of arguments and data on early detection,
      this is something that each physician clearly can and should do. A reduced risk
      for lung cancer may begin as early as 5 years after cessation of cigarette use.
      Huuskonen has proposed conceptualizing screening as a coordinated intervention
      with the goal of identifying populations at risk and working to modify that risk.
      Primary prevention should be central to any efforts to reduce mortality from lung
      cancer, and attention to this area needs to increase despite the difficulties and
      frustration. Despite declining percentages of smokers in the population as a
      whole, it is estimated that more than 3000 teenagers become regular smokers each
      day in the United States. In this environment, the question of whether to
      recommend a CXR or sputum for early detection is not going to disappear in the
      near future. The NCI has recognized the persistent and important nature of this
      debate and is currently funding the Prostate, Lung, Colon and Ovary Cancer
      Screening Trial. This is a large and powerful randomized study of men and women
      aged 60 to 74. The lung cancer arm is designed to look at the usefulness of a
      yearly CXR intervention in reducing cancer-specific mortality. The overall power
      of the study (based on national mortality data) is 0.99 for a 15% reduction in
      lung cancer mortality and 0.89 for a 10% reduction, with differentially better
      sensitivity in men than women. The study is currently in progress at multiple
      sites and will be completed over the next 12 to 14 years. In the meantime, what
      is the right approach? It is useful in considering this question to return to the
      concepts of early detection, screening, and case finding. 1. Early detection in
      lung cancer remains a concept of uncertain applicability because of the unknowns
      and variability in the natural history of the disease. The available, accessible,
      and acceptable detection tools appear to be inadequate by current evidence. This
      is not a static field, however, and new work in the area of biomarkers carries
      promise for significantly more sensitive and specific techniques. Tockman and
      colleagues conclude that early detection is conceptually sound, although not
      currently practical, and further research may expand the role of intervention. In
      the end, a judgement on early detection in lung cancer must be linked to the
      proposed setting--screening or case finding. 2. Screening, defined as the
      application of a test to the general population to define disease risk further
      with the implied benefit of improved treatment and outcome, cannot be recommended
      for lung cancer. This is the perspective of the major organizations cited
      previously, and it is based on admittedly imperfect but nonetheless convincing
      data. 3. Case finding, the situation of the patient who seeks care and is
      available for informed discussion and negotiation on possible testing, is a
      potentially different situation.(ABSTRACT TRUNCATED)

PMID- 8569302
TI  - Prostate cancer screening.
AB  - Prostate cancer is a common cancer and a leading cause of cancer death in men. It
      is potentially detectable at early, possibly curative stages through various
      combinations of testing, including DRE, PSA, and TRUS of the prostate. Still
      unproven is the effectiveness of prostate cancer treatment, and because of that
      lack of proof, the optimal screening strategies are also elusive. It is possible
      that what is known as prostate cancer today may be, in fact, multiple entities
      with different natural histories, different treatment needs, and, consequently,
      different screening strategies. The role of informed consent has been suggested
      as a means to involve patients in the decision process, especially because the
      literature presents an environment of intense controversy. It is hoped that the
      PIVOT trial or similar efforts and further research into the basic mechanisms of
      the disease will provide clearer answers in the future.

PMID- 8569303
TI  - Skin cancer screening.
AB  - The key to reducing morbidity and mortality from skin cancer is early detection.
      Prevention through education is, of course, ultimately the best outcome of
      collective human efforts. Many questions are still unresolved, but skin cancer
      screening by general internists, family practitioners, dermatologists, and other
      health professionals could prove cost-effective and reliable. As more knowledge
      becomes available, clinicians will have the resources to improve skills in
      prevention and early detection.

PMID- 8569304
TI  - An open environment for quantitative analysis of left ventricular function using
      ultrasound images.
AB  - We have developed an open environment for quantitative analysis of left
      ventricular function using ultrasound images. The system is primarily intended
      for experimental purposes, i.e. clinical research and the evaluation of
      quantification algorithms. The modular design allows easy expansion with new
      analysis methods. The core of our system is the user-interface and image
      presentation. Image analysis methods are included as a set of tools available to
      the operator. Using this approach, the expensive, expert knowledge of the
      cardiologist is used more efficiently than in most delineation systems. During
      delineation, images of a complete heart cycle can be simultaneously displayed
      dynamically ('cine mode') in a separate window. This feature improves visual edge
      perception and enables accurate determination of the endocardium even in cases of
      very poor echogenicity. The resulting contour can be corrected locally by
      interactive modification using 'rubber banding'. After delineation of the images
      from different echocardiographic views, volume, ejection fraction, and regional
      wall motion are determined. Studies using contrast-enhanced echocardiography can
      be quantified by image intensity analysis in a region of interest in order to
      determine myocardial perfusion. We evaluated our method by quantifying
      echocardiographic studies from 12 healthy volunteers. We compared the results
      with magnetic resonance imaging and concluded that there was no significant
      difference in volume and ejection fraction calculated from both modalities.
      Moreover, the image display features and contour correction methods were greatly
      appreciated by the cardiologists who used the system.

PMID- 8569305
TI  - A case-based assistant for diagnosis and analysis of dysmorphic syndromes.
AB  - This report describes the development of a case-based reasoning (CBR) system
      designed to provide assistance to specialists within the dysmorphology field. An
      interactive CBR model is described which aids medical experts in arriving at
      potential diagnoses, and has an explicit learning goal in order to provide
      further analytical assessment of syndrome categories. The complexity of this real
      world domain has highlighted a number of important empirical issues with respect
      to CBR techniques, which are discussed along with the system design.

PMID- 8569306
TI  - An essay on power of expert systems versus human expertise.
AB  - In connection with several recent studies of medical informatics, the usefulness
      and use of expert systems have been both criticized and defended. We have
      examined the issue of the inference power of expert systems compared to that of
      human experts. At an abstract level we have shown that there is no doubt that
      expert systems could successfully complement human experts within strictly
      limited and well-defined specialties, and actually be of reasonable aid in
      diagnosis, provided that the expert systems have been correctly and effectively
      elaborated. Also practical experiments were conducted with our recently
      implemented expert system.

PMID- 8569307
TI  - Development of security guidelines for existing healthcare systems.
AB  - As modern healthcare establishments become increasingly dependent upon
      information systems it is vital to ensure that adequate security is present to
      safeguard the confidentiality and integrity of data and the availability of
      systems. Whilst this is now generally recognized in the design of new systems,
      many existing operational systems have been implemented without security in mind.
      This paper describes the need for a standardized approach in the protection of
      existing healthcare systems within Europe and presents an overview of a new set
      of information security guidelines that have been developed specifically for the
      medical community. The guidelines discussed have been produced as a deliverable
      of the Commission of European Communities (CEC) SEISMED (Secure Environment for
      Information Systems in Medicine) project, under the Advanced Informatics in
      Medicine (AIM) programme.

PMID- 8569308
TI  - 3D colour visualization of label images using volume rendering techniques.
AB  - Volume rendering methods for the visualization of 3D image data sets have been
      developed and collected in a C library. The core algorithm consists of a
      perspective ray casting technique for a natural and realistic view of the 3D
      scene. New edge operator shading methods are employed for a fast and information
      preserving representation of surfaces. Control parameters of the algorithm can be
      tuned to have either smoothed surfaces or a very detailed rendering of the
      geometrical structure. Different objects can be distinguished by different
      colours. Shadow ray tracing has been implemented to improve the realistic
      impression of the 3D image. For a simultaneous representation of objects in
      different depths, hiding each other, two types of transparency mode are used
      (wireframe and glass transparency). Single objects or groups of objects can be
      excluded from the rendering (peeling). Three orthogonal cutting planes or one
      arbitrarily placed cutting plane can be applied to the rendered objects in order
      to get additional information about inner structures, contours, and relative
      positions.

PMID- 8569309
TI  - Understanding clinical narrative text.
AB  - A linguistic analysis of the narrative which appears in patient documents, in the
      domain of urology, has shown that the information is conveyed by a small number
      of semantic statement types composed of syntactic combinations of medical and
      English word classes. It has been shown that words from different classes
      occurring in the diagnosis for the patient disease follow some regular
      grammatical rules. This impressive linguistic regularity in clinical narrative
      has made it encouraging to develop a recognizer which is capable of recognizing
      disease diagnosis in the narrative clinical documents in the domain of urology.
      The recognizer was implemented using the C language. This recognizer output
      information which could be refined to a form suitable for management by a
      database management system for further computerized information processing.

PMID- 8569310
TI  - The medical folder as an active tool in defining the clinical decision-making
      process.
AB  - Whenever the user of a consultation system needs to know a large amount of
      information items that are possibly inter-related, a system that is able to
      cooperate with the user can simplify the interaction and increase its speed. In
      fact, these systems can recognize the goals of the user, individuate the
      information related to his goals, and finally focus their attention on this
      information [1]. This paper describes research work on the design and creation of
      a medical folder management system capable of establishing cooperative dialogue
      with users who have access to the information contained therein. Particular
      attention has thus been paid to the problems of man-computer dialogue and user
      models. The research work has addressed the problem of integrating into the
      system knowledge about the medical domain and users (physicians are only used for
      the time being), which are both necessary to activate a cooperative dialogue.
      After analysing the literature on the problems of user models, this paper
      presents and formalizes a study performed at the IVth Surgical Clinic of the Rome
      University Umberto I General Hospital to identify and represent how, when, and
      with what goals the physician consults the medical folder, as well as the
      dialogue procedures he normally adopts. The paper also illustrates important
      characteristics of the CADMIO prototype, which has been developed since the study
      was made. CADMIO stores information about users for use in recognizing and
      interpreting their behaviour, providing help, and in acquiring and returning
      further information. Whilst always bearing in mind the physician's pre
      established goals, it structures information to facilitate his consultation
      activity, offering him options for the retrieval of further information
      semantically linked to that already obtained.

PMID- 8569311
TI  - [Health care and ISO 9000: is quality assurance for entire hospitals possible?].

PMID- 8569312
TI  - [Prioritizing and transplantation. Which patient will receive the single
      available organ?].

PMID- 8569313
TI  - [SBU does not make statements on mammographic screening without basic data].

PMID- 8569314
TI  - [Diagnosis of leg ulcers].

PMID- 8569315
TI  - [Healing of leg ulcers with occlusive dressings].

PMID- 8569316
TI  - [Specialists should decide if oral contraceptives are suitable in cases of
      predisposition to thrombosis].

PMID- 8569317
TI  - [Handicap as a wrong concept in society. All should follow the WHO definition].

PMID- 8569318
TI  - [Adolescents manage their crises without "happy pills"].

PMID- 8569319
TI  - [Participation in a Balint group is good for the patient-physician relation].

PMID- 8569320
TI  - [Physicians sued for missed information. Demand a "receipt" to be on the safe
      side!].

PMID- 8569321
TI  - [Swedish mammographic screening. Annual costs 106 millions crowns, 2,7 percent of
      participants are further examined].

PMID- 8569322
TI  - [Vaccination against whooping cough is being reintroduced].

PMID- 8569323
TI  - [Suspected malignancy of the gallbladder: choose open surgery instead of
      laparoscopy].

PMID- 8569324
TI  - [Port site metastases after laparoscopy. Two cases of tumor seeding from
      gallbladder cancer].

PMID- 8569325
TI  - [Human victory over the smallpox virus. Only the death-blow remains].

PMID- 8569326
TI  - [Swedish polio-protection is satisfactory. But before the disease is eradicated,
      everybody should be vaccinated].

PMID- 8569327
TI  - [Poliomyelitis may be eradicated. But WHO needs help with vaccine, monitoring and
      laboratory resources from developed countries].

PMID- 8569328
TI  - [Examination of children and adolescents who attempted suicide. No overmortality
      could be detected].

PMID- 8569329
TI  - [Increased antibiotic resistance of intestinal bacteria].
AB  - A survey of bacterial resistance rates in four intensive care units (ICU) at a
      Swedish university hospital showed an increase of ampicillin resistant
      enterococci from 3.2 percent 1993 to 17.7 percent 1994. This increase of
      ampicillin-resistant enterococci was due to an increase of Enterococcus faecium
      with chromosomal ampicillin resistance. The survey also showed a relative high
      level of cefalosporine resistance, at the ICUs, among Enterobacter spp and to
      some extent among Escherichia coli and Klebsiella spp. A simultaneously performed
      survey of all blood isolates from the four hospitals in the county revealed the
      same development of resistance but the resistance rates were lower compared with
      the ICUs. To reduce the spread of resistant bacterial isolates there is a need
      for decreased and optimized antibiotic consumption as well as isolation of
      patients infected with resistant isolates.

PMID- 8569330
TI  - [Genetic diagnosis, future requirement for insurance? A questionable prognostic
      tool].

PMID- 8569331
TI  - [Intricate risk assessment in child insurance. Child Insurance Companies,
      Sweden].

PMID- 8569332
TI  - [Causes of fibromyalgia are both peripheral and central].

PMID- 8569333
TI  - [Report of a case. Horner syndrome caused by knife stab].

PMID- 8569334
TI  - [TV and sedentary life result in more overweight people].

PMID- 8569335
TI  - [Risk of life-threatening injury in every fifth lex Maria case. A risk-database
      is presented in a new information leaflet].

PMID- 8569336
TI  - [Physicians criticize cessation of screening].

PMID- 8569337
TI  - [Occupational therapy--a not sufficiently used resource in Swedish health care?].

PMID- 8569338
TI  - [Abolish forensic psychiatry! Offensive consequences after unjustified special
      treatment].

PMID- 8569339
TI  - [Why is split the normal dose into half?].

PMID- 8569340
TI  - [Increased knowledge is necessary for further talks about good death].

PMID- 8569341
TI  - [What is happening at the Amalgam unit in Uppsala?].

PMID- 8569342
TI  - [A national registry on diabetes does not improve the quality of diabetic care].

PMID- 8569343
TI  - [Accessible facts are necessary for the development of diabetic care].

PMID- 8569344
TI  - [Obesity may have a genetic background].

PMID- 8569345
TI  - [When is it justified to perform hysterectomy? The RAM (Rand Appropriateness
      Method) method helps to find a right therapeutic alternative].

PMID- 8569346
TI  - [Interposition of the tendon of the biceps. A complication of shoulder
      dislocation].

PMID- 8569347
TI  - [The hormone leptin reduces body weight. A mutant gene makes the mouse obese].
AB  - The existence of mice (ob/ob mice) with a genetic defect causing obesity and type
      II diabetes has been known since 1950. The mutated ob gene was recently
      identified and characterized. The gene encodes a 167 amino acid protein that has
      been given the name leptin, from the greek word leptos, meaning thin. The
      functionally active hormone, which is synthesised and secreted by adipocytes, is
      lacking in homozygote ob/ob mice, causing an increase in body fat. Injection of
      recombinant leptin in ob/ob mice induces loss of fat due to decreased appetite
      and increased energy expenditure. The ob gene product leptin acts via binding
      sites in the hypothalamus, where the centre for appetite and satiety is located.
      Research is now focused on the identification, characterization and cloning of
      leptin-receptors. Other mice, also with a genetic defect causing obesity and type
      II diabetes, do not respond to leptin treatment and are therefore suspected to
      have defective leptin receptors.

PMID- 8569348
TI  - [A woman with diffuse problems in her legs and back. Suspect obstruction of the
      pelvic vasculature!].

PMID- 8569349
TI  - [Nitrous oxide is superior to other anesthetics in colonoscopy].

PMID- 8569350
TI  - [Daily administration of nose drops can cause chronic nasal congestion].

PMID- 8569351
TI  - [Important examination in brain-damaged patients. Vision tests are needed for
      rehabilitation planning].

PMID- 8569352
TI  - [Comparison of patients admitted in the 1970's and 1990's. There are more violent
      criminals in Karsudden today].

PMID- 8569353
TI  - [Quality assurance of medical education. Test knowledge and follow up strictly].

PMID- 8569354
TI  - The gap generation.

PMID- 8569355
TI  - Taking "cryptogenic" out of fibrosing alveolitis.

PMID- 8569356
TI  - Angioplasty for lower-limb ischaemia: time for randomised controlled trials.

PMID- 8569357
TI  - Encouraging trials of labour for patients with previous caesarean birth.

PMID- 8569358
TI  - Xeroderma pigmentosum knockouts.

PMID- 8569359
TI  - Joint distraction for osteoarthritis.

PMID- 8569360
TI  - Ultrasonographic measurement of lower uterine segment to assess risk of defects
      of scarred uterus.
AB  - BACKGROUND: Ultrasonography has been used to examine the scarred uterus in women
      who have had previous caesarean sections in an attempt to assess the risk of
      rupture of the scar during subsequent labour. The predictive value of such
      measurements has not been adequately assessed, however. We aimed to evaluate the
      usefulness of sonographic measurement of the lower uterine segment before labour
      in predicting the risk of intrapartum uterine rupture. METHODS: In this
      prospective observational study, the obstetricians were not told the
      ultrasonographic findings and did not use them to make decisions about type of
      delivery. Eligible patients were those with previous caesarean sections booked
      for delivery at our hospital. 642 patients underwent ultrasound examination at 36
      38 weeks' gestation, and were allocated to four groups according to the thickness
      of the lower uterine segment. Ultrasonographic findings were compared with those
      of physical examination at delivery. FINDINGS: The overall frequency of defective
      scars was 4.0% (15 ruptures, 10 dehiscences). The frequency of defects rose as
      the thickness of the lower uterine segment decreased: there were no defects among
      278 women with measurements greater than 4.5 mm, three (2%) among 177 women with
      values of 3.6-4.5 mm, 14 (10%) among 136 women with values of 2.6-3.5 mm, and
      eight (16%) among 51 women with values of 1.6-2.5 mm. With a cut-off value of 3.5
      mm, the sensitivity of ultrasonographic measurement was 88.0%, the specificity
      73.2%, positive predictive value 11.8%, and negative predictive value 99.3%.
      INTERPRETATION: Our results show that the risk of a defective scar is directly
      related to the degree of thinning of the lower uterine segment at around 37 weeks
      of pregnancy. The high negative predictive value of the method may encourage
      obstetricians in hospitals where routine repeat elective caesarean is the norm to
      offer a trial of labour to patients with a thickness value of 3.5 mm or greater.

PMID- 8569361
TI  - Occupational exposure to metal or wood dust and aetiology of cryptogenic
      fibrosing alveolitis.
AB  - BACKGROUND: We have previously suggested that cryptogenic fibrosing alveolitis
      (CFA) may be caused by occupational exposures, particularly to metal or wood
      dust. We have specifically investigated this hypothesis in a case-control study
      of patients with CFA. METHODS: We obtained lifetime occupational histories by
      postal questionnaire from 218 patients with CFA and 569 controls matched for age,
      sex, and community, living in the Trent region of the UK. Information was
      subsequently verified by telephone interview in 165 cases and 408 controls. Serum
      IgE, rheumatoid factor, and antinuclear antibodies and skin sensitivity to common
      allergens were measured in cases and in one matched control for each. FINDINGS:
      The relative risk of CFA, after adjustment for smoking, was significantly
      increased in relation to questionnaire-reported exposure to metal dust (odds
      ratio 1.68 [95% CI 1.07-2.65], p = 0.024) or to wood dust (1.71 [1.01-2.92], p =
      0.048). Similar results were obtained with the telephone interview data.
      Significant exposure-response effects were found for both metal-dust and wood
      dust exposure. CFA was also associated with the presence of rheumatoid factor or
      antinuclear antibodies, but not with positive allergen skin tests or raised IgE
      concentrations. There was no evidence of interaction between the effects of
      rheumatoid factor, antinuclear antibodies, positive skin allergen tests, or IgE
      concentrations and exposure to metal or wood dust. The combined aetiological
      fraction attributable to exposure to metal or wood dust was of the order of 20%.
      INTERPRETATION: Occupational exposures to metal or wood dust are independent risk
      factors for CFA. Avoidance or limitation of these exposures may provide an
      opportunity to prevent the disease.

PMID- 8569362
TI  - Mild hypothermia increases blood loss and transfusion requirements during total
      hip arthroplasty.
AB  - BACKGROUND: In-vitro studies indicate that platelet function and the coagulation
      cascade are impaired by hypothermia. However, the extent to which perioperative
      hypothermia influences bleeding during surgery remains unknown. Accordingly, we
      tested the hypothesis that mild hypothermia increases blood loss and allogeneic
      transfusion requirements during hip arthroplasty. METHODS: Blood loss and
      transfusion requirements were evaluated in 60 patients undergoing primary,
      unilateral total hip arthroplasties who were randomly assigned to normothermia
      (final intraoperative core temperature 36.6 [0.4] degrees C) or mild hypothermia
      (35.0 [0.5] degrees C). Crystalloid, colloid, scavenged red cells, and allogeneic
      blood were administered by strict protocol. FINDINGS: Intra- and postoperative
      blood loss was significantly greater in the hypothermic patients: 2.2 (0.5) L vs
      1.7 (0.3) L, p < 0.001). Eight units of allogeneic packed red cells were required
      in seven of the 30 hypothermic patients, whereas only one normothermic patient
      required a unit of allogeneic blood (p < 0.05 for administered volume). A typical
      decrease in core temperature in patients undergoing hip arthroplasty will thus
      augment blood loss by approximately 500 mL. INTERPRETATION: The maintenance of
      intraoperative normothermia reduces blood loss and allogeneic blood requirements
      in patients undergoing total hip arthroplasty.

PMID- 8569363
TI  - Comparison of leg compression stocking and oral horse-chestnut seed extract
      therapy in patients with chronic venous insufficiency.
AB  - BACKGROUND: Diseases of the venous system are widespread disorders sometimes
      associated with modern civilisation and are among the major concerns of social
      and occupational medicine. This study was carried out to compare the efficacy
      (oedema reduction) and safety of compression stockings class II and dried horse
      chestnut seed extract (HCSE, 50 mg aescin, twice daily). METHODS: Equivalence of
      both therapies was examined in a novel hierarchical statistical design in 240
      patients with chronic venous insufficiency. Patients were treated over a period
      of 12 weeks in a randomised, partially blinded, placebo-controlled, parallel
      study design. FINDINGS: Lower leg volume of the more severely affected limb
      decreased on average by 43.8 mL (n = 95) with HCSE and 46.7 mL (n = 99) with
      compression therapy, while it increased by 9.8 mL with placebo (n = 46) after 12
      weeks therapy for the intention-to-treat group (95% CI: HCSE: 21.1-66.4;
      compression: 30.4-63.0; placebo: 40.0-20.4). Significant oedema reductions were
      achieved by HCSE (p = 0.005) and compression (p = 0.002) compared to placebo, and
      the two therapies were shown to be equivalent (p = 0.001); in this design,
      however, compression could not be proven as standard with regard to oedema
      reduction in the statistical test procedure. Both HCSE and compression therapy
      were well tolerated and no serious treatment-related events were reported.
      INTERPRETATION: These results indicate that compression stocking therapy and HCSE
      therapy are alternative therapies for the effective treatment of patients with
      oedema resulting from chronic venous insufficiency.

PMID- 8569364
TI  - Increased risk for myelodysplastic syndromes in individuals with glutathione
      transferase theta 1 (GSTT1) gene defect.
AB  - BACKGROUND: The glutathione S-transferases (GST) mediate exposure to various
      cytotoxic and genotoxic agents, including those associated with increased risk of
      the myelodysplastic syndromes (MDS). Both GST M1 (GSTM1) and GST theta 1 (GSTT1)
      genes have a "null" variant allele, in which the entire gene is absent. We tested
      whether the homozygous null genotype of GSTM1 and GSTT1 altered the risk for MDS.
      METHODS: In a hospital-based case-control study we analysed lymphocyte or bone
      marrow DNA samples from 96 patients with MDS and 201 cancer-free controls of
      similar age, race, and sex. We have restricted our report to the 92 white MDS
      patients. We analysed GSTM1 and GSTT1 genotypes by PCR. FINDINGS: The frequency
      of the GSTT1 null genotype was higher among MDS cases (46%) than among controls
      (16%). Inheritance of the GSTT1 null genotype conferred a 4.3-fold of MDS (odds
      ratio 4.3, 95% CI 2.5-7.4, p < 0.00001). The GSTM1 null genotype was not
      associated with increased risk of MDS (odds ratio 0.8, 0.5-1.3). INTERPRETATION:
      Individuals with the GSTT1 null genotype may have enhanced susceptibility to MDS.
      The mechanism might involve decreased detoxification of environmental or
      endogenous carcinogens.

PMID- 8569365
TI  - Treatment with angiotensin-converting-enzyme inhibitor for epirubicin-induced
      dilated cardiomyopathy.
AB  - BACKGROUND: Anthracycline chemotherapy in cancer can cause severe, frequently
      fatal congestive heart failure (CHF), the first-line treatment for which is
      diuretics and digoxin. We have studied the use of an angiotensin-converting
      enzyme (ACE) inhibitor added as a third agent. METHODS: In an observational study
      in hospital and as outpatients, 92 patients with advanced breast cancer were
      treated with epirubicin at a cumulative dose of 360 to 1000 mg/m2 (median 1000).
      Of 85 evaluable, nine developed life-threatening CHF at 1.5 to 13 months after
      ending epirubicin. Left ventricular ejection fraction (LVEF) decreased from
      normal to 18 to 35%. All received frusemide and digoxin, and then, after
      transient clinical relief, enalapril or ramipril (initially 1.25 mg orally daily,
      increasing to 10-15 mg after 4-6 weeks). FINDINGS: Eight of the nine patients
      deteriorated while on digoxin/diuretic. Within 3 months of starting the ACE
      inhibitor in these patients, LVEF had increased to normal or near normal. Only
      one patient died in heart failure. Follow-up ranged from 11 to 42 months (median
      26). The ACE inhibitor was well-tolerated, with no first-dose hypotension, except
      for one patient who discontinued treatment after 6 months because of persistent
      cough. Two others discontinued treatment with their ACE inhibitor after 22 and 28
      months because they felt well. Survival in the nine patients was similar to that
      of those who did not develop CHF. INTERPRETATION: Our experience suggests that
      treatment of anthracycline-induced CHF with an ACE inhibitor should start soon
      after clinical improvement on digoxin/diuretic regardless of the severity of
      symptoms rather than waiting for clinical deterioration.

PMID- 8569367
TI  - Drug policy: should the law take a back seat?

PMID- 8569366
TI  - A woman with bone pain, fractures, and malabsorption.

PMID- 8569368
TI  - Is vascular smooth muscle cell proliferation beneficial?

PMID- 8569369
TI  - The Great Hanshin earthquake.

PMID- 8569370
TI  - Fetal and neonatal environment has influence on brain development.

PMID- 8569371
TI  - What prospects for hormonal contraceptives for men?

PMID- 8569372
TI  - Unusual skin injury from lightning.

PMID- 8569373
TI  - Vitamin A and birth defects.

PMID- 8569374
TI  - Vitamin A and birth defects.

PMID- 8569375
TI  - Somnolence associated with melatonin deficiency after pinealectomy.

PMID- 8569376
TI  - Rebound hypoglycaemia after intravenous glucose in anorexia nervosa.

PMID- 8569377
TI  - Atopic dermatitis and staphylococcal superantigens.

PMID- 8569378
TI  - Haematogenous dissemination of prostate epithelial cells during surgery.

PMID- 8569379
TI  - Haematogenous dissemination of prostate epithelial cells during surgery.

PMID- 8569380
TI  - Haematogenous dissemination of prostate epithelial cells during surgery.

PMID- 8569381
TI  - Neuropsychiatric reactions with mefloquine chemoprophylaxis.

PMID- 8569382
TI  - Gut inflammation in children with cystic fibrosis on high-dose enzyme
      supplementation.

PMID- 8569383
TI  - Undisclosed prevalent HIV disease in district general hospitals in London.

PMID- 8569384
TI  - HIV-1 subtype B in west Africa.

PMID- 8569386
TI  - Polymerase chain reaction of cerebrospinal fluid to diagnose Whipple's disease.

PMID- 8569385
TI  - CD4 lymphopenia in very elderly people.

PMID- 8569387
TI  - Bad research is not audit.

PMID- 8569388
TI  - Down's syndrome screening in UK.

PMID- 8569389
TI  - Ethics committees.

PMID- 8569390
TI  - Formulation of guidelines for treatment.

PMID- 8569391
TI  - Nutritional status in rural Nigerians.

PMID- 8569392
TI  - Dermatology today in the UK.

PMID- 8569393
TI  - Dermatology today in the UK.

PMID- 8569394
TI  - Poetry helps healing.

PMID- 8569395
TI  - Severe hyperkalaemia with nafarelin.

PMID- 8569396
TI  - Variation in protection by BCG.

PMID- 8569397
TI  - Variation in protection by BCG.

PMID- 8569398
TI  - Foreign aid and tuberculosis control policy in the Federated States of
      Micronesia.

PMID- 8569399
TI  - Acute myocardial infarction after prostatectomy.

PMID- 8569400
TI  - Pitfalls of PCR: misdiagnosis of cerebral nocardia infection.

PMID- 8569401
TI  - Hantavirus outbreak during military manoeuvres in Germany.

PMID- 8569402
TI  - Hantavirus pulmonary syndrome in Germany.

PMID- 8569403
TI  - Treatment of adult Still's disease with intravenous immunoglobulin.

PMID- 8569404
TI  - X-linked recessive inheritance in a family with isolated congenital alopecia.

PMID- 8569405
TI  - The painful eye.

PMID- 8569406
TI  - HHV8 and skin cancers in immunosuppressed patients.

PMID- 8569407
TI  - Endocrine hypothesis for declining sperm count and rising incidence of cancer.

PMID- 8569408
TI  - Relevance to spina bifida of mutated methylenetetrahydrofolate reductase.

PMID- 8569409
TI  - Speech and swallowing rehabilitation following devastating caustic ingestion:
      techniques and indicators for success.
AB  - Caustic material ingestion, either accidental or intentional, may result in
      tissue and organ destruction leading to a wide range of complications, including
      loss of speech and the ability to eat. The esophagus can be reconstructed
      successfully, but reopening the larynx and upper airway poses a significant
      therapeutic dilemma. External reconstruction may put the neoesophagus at risk.
      Loss of the normal swallowing mechanism and the protective supraglottic
      structures often results in fatal aspiration. The authors present three cases of
      successful endoscopic laser recannulation of the larynx with esophageal
      replacement. The discussion includes surgical technique and the tools used to
      determine the success of the reconstruction, including computed tomographic
      scanning, modified barium swallow, placement of an upper esophageal anastomosis,
      psychologic support, and speech and swallowing therapy.

PMID- 8569410
TI  - Lasers in ophthalmology.
AB  - This article reviews the principle uses of ophthalmic lasers, providing
      historical background with an emphasis on new applications and areas of
      investigation. Ophthalmic photocoagulation was the first medical laser
      application and has restored or maintained vision in millions of people. More
      recently, photodisruption and, increasingly, ablation have gained prominence for
      treating a wide range of ocular pathology. The unique properties of lasers have
      also been harnessed for diagnostic purposes, with optical coherence tomography
      representing a significant improvement over existing imaging methods. Many
      ophthalmic applications of lasers have been developed, but the field is a dynamic
      one which continues to evolve along with laser technology itself.

PMID- 8569411
TI  - Antioxidants reduce corneal light scattering after excimer keratectomy in
      rabbits.
AB  - BACKGROUND AND OBJECTIVE: Excimer laser-corneal tissue interaction liberates
      highly reactive free radicals. Our aim was to determine if intraoperative
      application of antioxidants reduces the postoperative corneal light scattering by
      minimizing free radical-mediated cellular injury. STUDY DESIGN/MATERIALS AND
      METHODS: Phototherapeutic keratectomy (PTK) was performed in 20 rabbit eyes.
      Following 40-microns epithelial ablation, rabbits were divided into two groups
      and received 1-minute intraoperative application of either 50% dimethyl sulfoxide
      and 1% superoxide dismutase or vehicle (balanced salt solution) only. This was
      followed by a 6-mm diameter 100-microns PTK. Corneal light scattering was
      measured for 18 weeks using scatterometry. A light scattering index (SI) ranging
      from 0-10 was calculated; SI = 1 represents normal scattering. Light microscopic
      examination was performed in selected corneas. RESULTS: The mean baseline SI was
      similar for both groups (P = 0.95). Corneal haze followed a pattern of gradually
      increasing to peak at 2-3 weeks, and regressing partially thereafter. The
      decrease in mean SI following antioxidant application (dimethyl sulfoxide and
      superoxide dismutase) as compared to control group approached significance at 3
      weeks (0.1 > P > 0.05) and was highly significant at 9 weeks (P < 0.05).
      CONCLUSION: Intraoperative application of antioxidants decreases light scattering
      following excimer keratectomy in rabbit corneas. UV-induced free radicals may
      play a role in the pathogenesis of corneal light scattering following excimer
      laser keratectomy.

PMID- 8569412
TI  - Photodynamic laser cyclodestruction with chloroaluminum sulfonated phthalocyanine
      (CASPc) or Photofrin (PII) vs. Nd:YAG laser cyclodestruction in a pigmented
      rabbit model.
AB  - BACKGROUND AND OBJECTIVE: To investigate Photofrin (PII) and CASPc for
      photodynamic therapy (PDT) of the ciliary body in rabbits. STUDY DESIGN/MATERIALS
      AND METHODS: PII (10 mg/kg) or CASPc (1 mg/kg) was given by ear vein.
      Pharmacokinetics were studied in frozen sections by fluorescence microscopy (CCD
      camera based low light detection system with digital image processing) at 1 and
      24 h (8 rabbits; 16 eyes). Laser light was delivered (argon pumped dye laser; 630
      and 675 nm; 8 rabbits; 16 eyes) by contact fiberoptic. To compensate for iris
      attenuation, irradiance was 125 mW/cm2 (20, 40, 80, or 160 J/cm2). Controls (4
      rabbits; 8 eyes) received laser light without photochemicals (OD) and for
      comparison, continuous wave Nd:YAG laser by fiberoptic (0.8-1.2J; OS). RESULTS:
      Localization studies showed intravascular distribution with some selective
      ciliary body distribution at 24 h (PII > CASPc). Rabbits treated with PII or
      CASPc exhibited variable amounts of gross ciliary body edema, infarction, and
      necrosis by 24-48 h. This response was not seen in PDT control tissues; damage
      was seen in the iris and ciliary body, with partial vacuolization of the pigment
      epithelium. CONCLUSION: PDT may offer a more selective approach to ciliary body
      destruction. A small but significant thermal effect was seen during PDT from
      melanin photon uptake with damage to iris and ciliary body. Thermal damage and
      potential interaction with ocular visual pigments may limit use of these
      photochemicals and wavelengths for PDT of the ciliary body.

PMID- 8569413
TI  - Automated lesion placement in the rabbit eye.
AB  - BACKGROUND AND OBJECTIVE: The objective of this research was to build a prototype
      feedback control system to precisely place argon laser lesions on the retina for
      treatment of retinal disorders. STUDY DESIGN/MATERIALS, AND METHODS: The
      prototype feedback control system was tested by placing lesions at specific
      locations on the retina of pigmented rabbits to simulate the treatment of
      diabetic retinopathy, retinal breaks or tears, and a pre-programmed, two
      dimensional array of lesions was placed at a specific site. RESULTS: Results of
      feedback-controlled lesion placement performed in vivo on pigmented rabbits are
      presented. The ability to place lesions with automated feedback control is
      demonstrated. CONCLUSION: Automated feedback control placement of argon laser
      lesions is possible at a reasonable cost and has numerous therapeutic and safety
      benefits over current ballistic delivery.

PMID- 8569414
TI  - In vivo uptake of liposomal benzoporphyrin derivative and photothrombosis in
      experimental corneal neovascularization.
AB  - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) has been used successfully
      to occlude neovascularizations experimentally. We evaluated the vasoocclusive
      potential of benzoporphyrin derivative (BPD), a new photosensitizer currently in
      clinical trials. Since liposomally formulated BPD strongly binds to endogenous
      low density lipoproteins (LDL) after i.v. injection, LDL act as carrier to
      deliver BPD preferentially to proliferating endothelial cells. STUDY
      DESIGN/MATERIALS AND METHODS: Corneal neovascularizations in rabbits were used as
      model. Time-dependent uptake and retention of liposomal BPD were measured in vivo
      by monitoring the laser-induced fluorescence (LIF). Photothrombosis was induced
      using a dye laser emitting at 692 nm. RESULTS: A maximal BPD concentration was
      measured at 60-90 minutes postinjection determining the optimal time interval for
      treatment. Exposures as low as 10 J/cm2 allowed complete and irreversible
      neovascular occlusion as documented angiographically. Histology revealed
      selective endothelial damage, adjacent corneal stroma, or iris vessels, remained
      intact. Identical results were obtained using BPD directly complexed with LDL
      suggesting use of a LDL-mediated pathway. CONCLUSION: We suggest BPD-PDT for a
      selective treatment of neovascular diseases.

PMID- 8569415
TI  - Arousal-enhancing properties of the CB1 cannabinoid receptor antagonist SR
      141716A in rats as assessed by electroencephalographic spectral and sleep-waking
      cycle analysis.
AB  - The effects of the central (CB1) cannabinoid receptor antagonist SR 141716A on
      the sleep-waking cycle were investigated in freely-moving rats using time scoring
      and power spectral analysis of the electroencephalogram (EEG). Over a 4-hour
      recording period, SR 141716A (0.1, 0.3, 1, 3, and 10 mg/kg I.P.) dose-dependently
      increased the time spent in wakefulness at the expense of slow-wave sleep (SWS)
      and rapid eye movement sleep (REMS), delayed the occurrence of REMS but did not
      change the mean duration of REMS episodes. Moreover, the compound induced no
      change in motor behavior. At the efficient dose of 3 mg/kg I.P., SR 141716A
      reduced the spectral power of the EEG signals typical of SWS but did not affect
      those of wakefulness. Taken together, these results demonstrate that the EEG
      effects of SR 141716A reflect arousal-enhancing properties. In addition, the
      present study suggests that an endogenous cannabinoid-like system is involved in
      the control of the sleep-waking cycle.

PMID- 8569416
TI  - Effects of dietary phosphatidylcholine on memory in memory deficient mice with
      low brain acetylcholine concentration.
AB  - Data concerning the effect of phosphatidylcholine (PCh) administration on the
      improvement of memory in senile dementia of Alzheimer type are inconsistent,
      probably due to the different conditions under which studies were conducted.
      Animal studies provide a good model, but data on this is limited. We studied the
      effect of PCh on memory in memory deficient mice (Dull mice) with low brain
      acetylcholine (ACh) concentration and normal mice. Mice were fed 24% casein diet
      (control) or this diet supplemented with 2 or 8% egg yolk PCh from gestation
      (Experiment 1) and after weaning (Experiment 2). Memory acquisition and retention
      were studied by step-down type passive avoidance performance at 8 and 10 weeks
      old, respectively. Control group of Dull mice had poorer memories than that of
      the normal mice in Experiments 1 and 2. On the 2% PCh diet, Dull mice improved
      memory acquisition and retention in Experiment 1 and retention in Experiment 2.
      On the 8% PCh diet in Dull mice there was improvement of memory and retention in
      Experiment 1, but no effect was observed in Experiment 2 (P > 0.05). In the
      normal mice, the 2% PCh diet did not affect memory acquisition and retention,
      however on the 8% PCh diet, there was no or adverse effect. These results suggest
      that dietary supplementation of egg yolk PCh improves memory of Dull mice,
      particularly when given from gestation and that the 2% PCh diet elicits better
      response than the 8% PCh diet.

PMID- 8569417
TI  - Cerebroprotective action of the phospholipase inhibitor quinacrine in the
      ischemia/reperfused gerbil hippocampus.
AB  - The phospholipase inhibitor quinacrine (mepacrine; 5 mg/kg, i.p.) was tested for
      cerebroprotective activity in a gerbil stroke model. Quinacrine significantly
      reduced stroke injury assessed by locomotor activity monitoring and by
      histopathological measurement of hippocampal CA1 pyramidal cell loss. It is
      proposed that phospholipase activation, resulting from elevated levels of
      intracellular calcium, may contribute to ischemia-evoked neuronal injury.

PMID- 8569418
TI  - The rat, a useful animal model for pharmacological studies on apolipoprotein E.
AB  - Apolipoprotein E is a major protein component of lipoproteins and plays an
      important role in cholesterol transport. The structure of the gene and the
      polymorphism of apolipoprotein E have been studied in human and rat, which show
      similar structures of apolipoprotein E. The wide tissue distribution of this
      apolipoprotein suggests diverse functions like cholesterol distribution between
      cells, intracellular cholesterol trafficking and tissue reparation. Nevertheless,
      the presence of apolipoprotein E in atherosclerotic plaques and amyloid deposits
      in brains of Alzheimer's disease patients also indicate pathologic functions
      staying misunderstood. The aim of this paper is to review the present knowledge
      on the distribution of apolipoprotein E between the different organs with the
      related functions and to make an overview of the implications of this
      apolipoprotein is physiological events and pathological states in the rat. The
      rat is widely used for drug metabolism studies. Its serum levels are 5-10 times
      higher than in human and thus this animal provides an useful pharmacological
      model to elucidate the functions of apo E.

PMID- 8569420
TI  - Streptozotocin-induced diabetes increases fructose 2,6-biphosphate levels and
      glucose metabolism in thymus lymphocytes.
AB  - Acute effect of streptozotocin-induced diabetes on several parameters of glucose
      metabolism was investigated in thymus lymphocytes (thymocytes). The cells from
      diabetics rats accumulated in vitro about 2-fold more fructose 2,6-bisphosphate
      (Fru-2, 6-P2) in the presence of increasing glucose concentration than cells from
      normal rats. An increased production of lactate was also observed.
      Phosphofructokinase-1 (PFK-1) and phosphofructokinase-2 (PFK-2) activities were
      enhanced in cells from diabetic rats compared with those from normal rats. [U
      14C]glucose incorporation into glycogen was also increased in cells from diabetic
      rats and the 14CO2 liberation was lesser than in cells from normal animals. From
      these data it may be concluded that the response of thymocytes to streptozotocin
      induced diabetes is similar to that observed in other extrahepatic tissues.

PMID- 8569419
TI  - Sex differences in concentrations of exhaled nitric oxide and plasma nitrate.
AB  - Nitric oxide (NO) is generally considered as an endogenous vasoprotective agent.
      Various studies indicate that the female sex hormone estradiol, that contributes
      to the well known gender differences in cardiovascular disease, may enhance NO
      production. Thus we studied sex differences in NO-generation by measuring single
      breath NO-exhalation and plasma levels of nitrate (NO3), the stable endmetabolite
      of NO. In this observational trial 22 male and 21 female volunteers, 19 to 38
      years of age, were studied on 3 days at weekly intervals. Median concentrations
      of NO were 20 parts per billion (95% CI: 16 to 32 ppb) in women and 34 ppb (95%
      CI: 31 to 58 ppb) in men. The median plasma concentrations of NO3 were 14
      microM/L (95% CI: 11 to 23 microM/L) in women and 27 microM/L (95% CI: 24 to 47
      microM/L) in men. Thus, men exhaled 59% more NO (p < 0.001) and had 99% higher
      NO3 levels than women (p < 0.0001). Even when exhaled NO concentrations were
      corrected for body weight, men exhaled 50% more NO than women (p = 0.024). No
      significant changes in measured endpoints were seen during the menstrual cycle (p
      > 0.05) in women. In view of the diversity of NO-actions, the finding of marked
      sex differences in NO-production is basic to the elucidation of gender
      differences in a number of (patho)-physiologic conditions.

PMID- 8569421
TI  - Both ethanol and protein deficiency increase messenger RNA levels for pancreatic
      lithostathine.
AB  - Both ethanol abuse and protein deficiency are well known associations of chronic
      pancreatitis. An early event in chronic pancreatitis is the deposition of protein
      plugs in small pancreatic ducts, leading to ductular obstruction and acinar cell
      damage. Lithostathine, a pancreatic secretory protein, is a major organic
      component of protein plugs. The aim of this study was to determine the effect of
      chronic ethanol administration and dietary protein deficiency, separately and in
      combination, on messenger RNA (mRNA) levels for pancreatic lithostathine. Male
      Sprague-Dawley rats were fed in groups of four, for four weeks, protein
      sufficient and protein deficient diets with or without ethanol. Messenger RNA
      levels for pancreatic lithostathine were assessed in all four groups. Both
      ethanol and protein deficiency, separately and in combination, increased mRNA
      levels for lithostathine. Thus, both chronic ethanol consumption and dietary
      protein deficiency increase the capacity of the pancreatic acinar cell to
      synthesize lithostathine.

PMID- 8569422
TI  - Adenosine attenuation of isoproterenol-stimulated adenylyl cyclase activity is
      enhanced with aging in the adult heart.
AB  - Interstitial levels and release of adenosine have been shown to be greater for
      aged adult hearts compared to young adult hearts. Furthermore, blockade of A1
      adenosine receptors in the aged adult heart prevents the reduced contractile and
      metabolic response to isoproterenol. The aim of this study was to determine
      whether there is an enhanced antiadrenergic effect of adenosine in the aged adult
      heart. Ventricular membranes from young and aged adult hearts were incubated in
      the presence of isoproterenol (ISO) and phenylisopropyladenosine (PIA) either
      alone or in combination. Basal and ISO-enhanced adenylyl cyclase activity were
      significantly reduced in the membranes from aged rats. PIA alone, at 0.1 nM to
      100 microM, had no direct effect on basal adenylyl cyclase activity in membranes
      from either group. In the presence of either 100 nM or 1 microM ISO, 100 microM
      PIA significantly attenuated ISO-enhanced adenylyl cyclase activity to a greater
      extent in the aged adult heart membranes (78 or 48% for the aged vs. 37 or 25%
      for the young). Moreover, in the presence of 100 nM ISO the IC50 for the PIA
      concentration response curve was shifted to the left for the aged ventricular
      membranes as compared to the membranes from young adults (1.62 x 10(-7) M vs 1.5
      x 10(-6) M, aged vs young, respectively). The enhanced inhibition of adenylyl
      cyclase is associated with an increase in adenosine A1 receptor density (23.7 +/-
      3.5 vs 14.7 +/- 1.7 fmol/mg, aged vs young) and Kd (6.1 +/- 1.7 vs 2.2 +/- 0.5
      nM, aged vs young) in the aged adult heart membranes as determined by [3H]DPCPX
      binding. These results suggest that the reduced response to catecholamines in the
      aged adult heart may be due, at least in part, to an enhanced expression of the
      antiadrenergic effect of adenosine on beta-adrenergic receptor mediated
      activation of adenylyl cyclase.

PMID- 8569423
TI  - Effects of probucol on hypercholesterolemia-induced changes in antioxidant
      enzymes.
AB  - Effects of high cholesterol diet (0.5% and 1%) on the activity of antioxidant
      enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase
      (GSH-Px)] in the aortic tissue of rabbits were investigated in the absence or
      presence of probucol (0.5 gm/kg daily, orally). Five groups of ten rabbits each
      were studied. Group I, regular rabbit chow diet; Group II, chow + 0.5%
      cholesterol; Group III, chow + 0.5% cholesterol+probucol; Group IV, chow + 1%
      cholesterol and Group V, chow + 1% cholesterol+probucol. The aorta was removed at
      the end of 4 months for measurement of the antioxidant enzymes. An increase in
      activity of aortic antioxidant enzymes was noted in cholesterol-fed rabbits
      (Groups II and IV), being similar for SOD and catalase but higher for GSH-Px in
      Group IV as compared to Group II. Probucol was ineffective in altering this
      cholesterol-induced increase in enzyme activity except in Group III where it
      increased the activity of GSH-Px. These results suggest that aortic antioxidant
      enzymes are affected in hypercholesterolemia and that probucol is ineffective in
      altering the aortic antioxidant enzyme activity except GSH-Px activity which
      increased in 0.5% cholesterol-fed rabbits. The protective effects of probucol
      against hypercholesterolemic atherosclerosis may be partly due to an increase in
      the GSH-Px activity at low levels of hypercholesterolemia. At higher levels of
      hypercholesterolemia, the protective effects of probucol could be due to its
      antioxidant activity.

PMID- 8569424
TI  - Ranitidine increases the bioavailability of imbibed alcohol by accelerating
      gastric emptying.
AB  - To investigate the mechanism of the increase in alcohol bioavailability by
      ranitidine, we determined by nuclear scan the changes in gastric emptying of a
      10% ethanol solution (containing 0.3 g ethanol/kg body weight and 300 microCi of
      technetium-labeled diethylene triamine pentacetic acid) in 8 normal men, before
      and after treatment with 300 mg ranitidine orally each evening for 1 week. We
      compared these changes with those of ethanol bioavailability, calculated by
      integration of the Michaelis-Menten function over the entire alcohol curves after
      random i.v. and, on a separate day, oral administration of the same ethanol dose,
      pre- and post-ranitidine. With ranitidine, we found an acceleration of gastric
      emptying in 7 of 8 subjects, with 20% shortening of the time to 50% emptying
      (51.8 +/- 4.1 min vs 64.3 +/- 3.4, without ranitidine; P < .001 by paired t
      test). Despite the disappearance (from the stomach) of most of the dose by the
      end of the blood alcohol curves, only 83 +/- 4% reached the systemic blood vs 64
      +/- 4% without ranitidine (P < .02), most likely because of a shortened exposure
      of alcohol dehydrogenase to optimal ethanol concentrations. As a result, after
      oral but not intravenous alcohol administration, ranitidine increased blood
      alcohol concentrations (29 +/- 4 mg/dl vs 22 +/- 3, without ranitidine; P < .02),
      with a corresponding decrease in first pass metabolism of ethanol from 107 +/- 16
      mg/kg to 47 +/- 16 (P < .01).

PMID- 8569425
TI  - Circulating autoantibodies to a 240 kD fetal brain protein.
AB  - Antibodies (IgG and IgM) recognizing a 240 kD antigen of the cat fetal brain were
      found in sera of healthy people and in sera (IgG) obtained at uncomplicated
      delivery from the umbilical cord of the newborn infant. The method applied was
      immunoblotting. Using the same method, the 240 kD antigen could not be detected
      in the adult brain or other fetal tissues. It seems that the antigen is specific
      for the fetal brain. The role of the antigen and the origin of generation and
      significance of function of the antibodies in the circulation are the objects of
      our further studies.

PMID- 8569426
TI  - A melatonin binding site modulates the alpha 2-adrenoceptor.
AB  - The melanophores of the cuckoo wrasse (Labrus ossifagus L., a teleost fish) can
      aggregate and disperse their pigment granules. This migration is controlled by
      sympathetic nerves and a postsynaptic alpha 2-adrenoceptor. Melatonin was
      discovered because of its ability to aggregate pigment granules, hence we used
      the cuckoo wrasse melanophore as a model for studying the effect of melatonin at
      a cellular level. We found that melatonin had no aggregating effect; instead the
      hormone enhanced the actions of several alpha 2-agonists, such as noradrenaline,
      medetomedine and clonidine. When the melanophores were pre-aggregated in vitro by
      use of the alpha 2-agonist B-HT 920, the aggregation was not augmented after the
      addition of melatonin. Instead the pre-aggregated granules were dispersed. This
      suggests that melatonin has affinity for an alpha 2-adrenoceptor site that can
      modulate the effect of alpha 2-adrenoceptor agonists.

PMID- 8569427
TI  - Chemiluminescence detection of mono-, bis-, and tris-hydroperoxy triacylglycerols
      present in vegetable oils.
AB  - A reliable method was needed to analyze molecular species of oxidized vegetable
      oils. In order to accomplish this goal, mono-, bis-, and tris-hydroperoxides
      (Mono-OOH, Bis-OOH, and Tris-OOH, respectively) of triacylglycerols formed during
      autoxidation and photosensitized oxidation of oils were determined by reversed
      phase high-performance liquid chromatography in combination with
      chemiluminescence detection (CL-HPLC). Mono-OOH was the major species (96% of
      total hydroperoxides) in trioleoylglycerol [peroxide value (PV) 0.16 meg/kg], and
      Bis-OOH and Tris-OOH showed prolonged accumulation with photooxidation. This
      profile was confirmed in photooxidation of trilinoleoylglycerol and
      trilinoleoylglycerol. Soybean oil (PV 6 meq/kg) contained Mono-OOH oleoyl
      linoleoylglycerol as the main peroxidic molecular species (50% of total
      hydroperoxides). Mono-OOH trilinoleoylglycerol was the principal species (61% of
      total hydroperoxides) in safflower oil (PV 5 meq/kg), and Mono-OOH oleoyl-oleoyl
      linoleoylglycerol was the representative species (66% of total hydroperoxides) in
      olive oil (PV 3 meq/kg). The CL-HPLC method, which is specific for the detection
      of hydroperoxides, should prove useful in studies of triacylglycerol oxidation in
      foods and vegetable oils.

PMID- 8569428
TI  - In vitro oxidation of vitamins C and E, cholesterol, and thiols in rat brain
      synaptosomes.
AB  - Free radical-induced oxidation of vitamins C, E, sulfhydryl compounds, and
      cholesterol in brain synaptosomes from Fisher 344 rats was studied. The
      synaptosomes were incubated at 37 degrees C with 2,2'-azobis-(2-amidinopropane)
      dihydrochloride (AAPH), which undergoes thermal decomposition to yield free
      radicals. After incubation, the synaptosomes were sedimented, saponified, and
      extracted with hexane to isolate tocopherol and cholesterol. Ascorbate and
      tocopherol were assayed by liquid chromatography, cholesterol by gas
      chromatography, and total sulfhydryls by spectrophotometry. Under the in vitro
      conditions used in this study, the approximate order for the ease of oxidation of
      the various compounds was: ascorbate >>tocopherol > sulfhydryl compounds >>>
      cholesterol. However, tocopherol and sulfhydryl oxidation occurred even before
      all of the ascorbate had been consumed. Therefore, the fate of a specific
      antioxidant at a particular cellular location cannot be predicted with complete
      accuracy using the in vitro order for ease of oxidation shown here. Ascorbate may
      play a major role in protecting brain against oxidative damage because: (i)
      ascorbate concentration is high in brain, (ii) it can regenerate vitamin E from
      its radical oxidation product, and (iii) it is one of the first antioxidants to
      be consumed during oxidative reactions.

PMID- 8569429
TI  - Biodiscrimination of alpha-tocopherol stereoisomers during intestinal absorption.
AB  - Synthetic alpha-tocopherol (alpha-Toc) contains equal amounts of eight different
      stereoisomers, and the four stereoisomers with the 2R configuration are generally
      more active than their corresponding 2S-isomers. We investigated the
      biodiscrimination of alpha-Toc stereoisomers during intestinal absorption in situ
      and in vitro. Intestinal absorption of alpha-Toc stereoisomers was examined in
      situ in vitamin E-deficient rats with cannulated thoracic ducts. We found that
      the ratios of alpha-Toc stereoisomers in lymph of the all-rac-alpha-Toc group
      were the same as the administered alpha-Toc stereoisomers, and 2R-isomers
      occupied approximately 50% of absorbed alpha-Toc. The uptake of alpha-Toc
      stereoisomers also was measured using Caco-2 cells cultured on filter membranes.
      The concentration of RRR-alpha-Toc in Caco-2 cells was not significantly
      different from that of SRR-alpha-Toc. Therefore, the discrimination of alpha-Toc
      stereoisomers does not occur during absorption in small intestine, suggesting the
      liver as source for the biodiscrimination.

PMID- 8569430
TI  - Sesame seed and its lignans produce marked enhancement of vitamin E activity in
      rats fed a low alpha-tocopherol diet.
AB  - Three series of experiments demonstrated that sesame seed and its lignans cause
      significant elevation of alpha-tocopherol content in rats. In Experiment 1, 20%
      sesame seed (with a negligible amount of alpha-tocopherol) supplementing 10
      (low), 50 (normal), or 250 (high) mg/kg alpha-tocopherol diets (protein and fat
      concentrations in diets were adjusted to 200 and 110 g/kg, respectively) all
      caused a significant increase of alpha-tocopherol in the blood and tissue of
      rats. In Experiment 2, groups of rats were fed five different diets: a vitamin E
      free control diet, a low alpha-tocopherol diet, and three low alpha-tocopherol
      diets supplemented with 5, 10, and 15% sesame seed. Changes in lipid peroxides in
      liver, red blood cell hemolysis, and pyruvate kinase activity, as indices of
      vitamin E deficiency, were examined. These indices were high in the low alpha
      tocopherol diet, whereas supplementation with even 5% sesame seed suppressed
      these indices completely and caused a significant increase of alpha-tocopherol
      content in the plasma and liver. In Experiment 3, two diets containing sesame
      lignan (sesaminol or sesamin) and low alpha-tocopherol were tested. Results in
      both of the sesame lignan-fed groups were comparable to those observed in the
      sesame seed-fed groups as shown in Experiment 2. These experiments indicate that
      sesame seed lignans enhance vitamin E activity in rats fed a low alpha-tocopherol
      diet and cause a marked increase in alpha-tocopherol concentration in the blood
      and tissue of rats fed an alpha-tocopherol-containing diet with sesame seed or
      its lignans.

PMID- 8569431
TI  - Suppression by carotenoids of microcystin-induced morphological changes in mouse
      hepatocytes.
AB  - Microcystin-LR is a liver tumor promoter in the okadaic acid class, a group of
      potent inhibitors of protein phosphatases 1 and 2A. Because of inhibition of
      protein phosphatases, microcystin-LR induces hyperphosphorylation of cellular
      proteins, including cytoskeletal proteins--cytokeratins 8 and 18--and causes
      morphological changes in mouse hepatocytes in primary culture. We studied the
      effects of carotenoids to antagonize microcystin-LR-induced morphological changes
      in hepatocytes. beta-carotene (100 nM to 100 microns) suppressed the
      morphological changes induced by 100 nM microcystin-LR in a dose-dependent
      manner. Other carotenoids tested exerted similar suppressive effects, although
      retinoids, such as all-trans retinol, all-trans retinoic acid, and 9-cis retinoic
      acid, were only weakly suppressive. The relative potency of the suppression
      correlated significantly with the number of conjugated double bonds in the trans
      configuration. beta-carotene strongly suppressed the hyperphosphorylation of
      cellular proteins induced by microcystin-LR without significant changes in the
      basal phosphorylation level. Other antioxidants, such as alpha-tocopherol, did
      not protect the cells against microcystin-LR. Taken together, the antagonistic
      effects of carotenoids against microcystin-LR are difficult to explain by their
      antioxidant or provitamin A activities. Suppression of the hyperphosphorylation
      of cellular proteins may be a novel mechanism by which carotenoids inhibit tumor
      promotion.

PMID- 8569432
TI  - Dietary menhaden oil enhances mitomycin C antitumor activity toward human mammary
      carcinoma MX-1.
AB  - In the present study, we investigated the effects of high levels of dietary fish
      oil on the growth of MX-1 human mammary carcinoma and its response to mitomycin C
      (MC) treatment in athymic mice. We found that high levels of dietary fish oil
      (20% menhaden oil + 5% corn oil, w/w) compared to a control diet (5% corn oil,
      w/w) not only lowered the tumor growth rate, but also increased the tumor
      response to MC treatment. We also found that high levels of dietary fish oil
      significantly increased the activities of tumor xanthine oxidase and DT
      diaphorase, which are proposed to be involved in the bioreductive activation of
      MC. Since menhaden oil is highly unsaturated, its intake caused a significant
      increase in the degree of fatty acid unsaturation in tumor membrane
      phospholipids. This alteration in tumor membrane phospholipids made the tumor
      more susceptible to oxidative stress, as indicated by the increased levels of
      both endogenous lipid peroxidation and protein oxidation after feeding the host
      animals the menhaden oil diet. In addition, the tumor antioxidant enzyme
      activities, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase
      (GPOx), and glutathione S-transferase peroxidase (GSTPx), were all significantly
      enhanced by feeding a diet high in fish oil. MC treatment caused further
      increases in tumor lipid peroxidation and protein oxidation, as well as in the
      activities of CAT, SOD, GPOx, and GSTPx, suggesting that MC causes oxidative
      stress in this tumor model which is exacerbated by feeding a diet high in
      menhaden oil. Thus, feeding a diet rich in menhaden oil decreased the growth of
      human mammary carcinoma MX-1, increased its responsiveness to MC, and increased
      its susceptibility to endogenous and MC-induced oxidative stress, and increased
      the tumor activities of two enzymes proposed to be involved in the bioactivation
      of MC, that is, DT-diaphorase and xanthine oxidase. These findings support a role
      of these two enzymes in the bioactivating of MC and indicate that the type of
      dietary fat may be important in tumor response to therapy.

PMID- 8569433
TI  - Phospholipid profiling of sediments using phosphorus-31 nuclear magnetic
      resonance.
AB  - A phosphorus-31 nuclear magnetic resonance method has been developed for the
      determination of aquatic sediment phospholipid profiles that may be generally
      applied to all soils and deposits containing viable cellular material. A method
      of scrubbing chloroform/methanol extracts with potassium acid phosphate overcomes
      adverse signal broadening from the mineral component, permitting eleven sediment
      phospholipids to be determined at the quantitative level.

PMID- 8569434
TI  - Urinary malondialdehyde-equivalents during ingestion of meat cooked at high or
      low temperatures.
AB  - Excretion of malondialdehyde (MDA)-generating substances in the urine has been
      suggested as an indicator of in vivo lipid peroxidation. However, MDA in the
      urine also reflects the amount of lipid peroxidation products consumed in the
      diet. We determined MDA as the thiobarbituric acid (TBA)-MDA complex in urine of
      19 healthy adults (10 male and 9 female) fed large quantities (3.6-4.1 g/kg body
      weight) of ground beef cooked at a low or a high temperature. Subjects ate a
      controlled diet with no alcohol or nutritional supplements. For 7 d they consumed
      ground beef cooked at 100 degrees C for 20 min (low-temperature meat) followed by
      7 d with meat fried at 250 degrees C for 22 min (high-temperature meat). Prior to
      the study, subjects consumed their normal free choice diet with moderate amounts
      of meat. The concentration of MDA in urine at baseline was 2.1 +/- 0.3 mumol TBA
      MDA equivalents/day (mean +/- SEM). After 7 d of low-temperature meat, urinary
      TBA-MDA equivalents increased to 23.1 +/- 1.4 mumol/d. Urinary TBA-MDA
      equivalents were consistently lower (6.9-8.0 mumol/d) 1, 2, 3, and 7 d after
      subjects changed to high-temperature meat. After 7 d of treatment, 97% of the MDA
      equivalents in the meat was recovered in 24-h urine samples. The low temperature
      meat had 3-4 times more MDA than did the high-temperature meat. These data
      indicate that the amount of meat eaten and the cooking procedures used can
      dramatically alter urinary MDA. Dietary sources of MDA must be controlled if
      urinary MDA is to be used as an indicator of oxidative stress.

PMID- 8569435
TI  - Inhibition of cholesterol synthesis and hepatic 3-hydroxy-3-methylglutaryl--CoA
      reductase in rats by simvastatin and pravastatin.
AB  - In this communication we attempt to provide one possible explanation for the
      observed differences regarding kinetics and distribution between simvastatin and
      pravastatin. Rats treated with simvastatin or pravastatin exhibited a reduction
      in the incorporation of [2-(14)C] acetate into liver cholesterol and displayed
      lower plasma mevalonate levels as compared to control animals. Moreover, both the
      total and dephosphorylated 3-hydroxy-3-methylglutaryl--CoA (HMG-CoA) reductase
      (EC 1.1.1.34) activities, particularly 1 h after treatment, were greatly reduced
      in liver microsomes obtained from simvastatin-treated as compared to control
      rats. During the same time frame, these parameters were actually elevated with
      pravastatin treatment. It is known that HMG-CoA reductase synthesis and activity
      increase following their competitive inhibition. Our results suggest that
      pravastatin, at 1 h following treatment, was no longer bound to the enzyme;
      however, it had entered the liver because its inhibitory effect on cholesterol
      synthesis was manifest at early times after administration. These data provide a
      plausible rationale for the earlier observation that activity of simvastatin
      persists longer in plasma than does that of pravastatin.

PMID- 8569436
TI  - Low-fat diets do not lower plasma cholesterol levels in healthy men compared to
      high-fat diets with similar fatty acid composition at constant caloric intake.
AB  - In most studies reporting the effects of high-fat (HF) and low-fat (LF) diets on
      human plasma fatty acids (FA) and lipoprotein levels, the design involved adding
      to the diet an oil that had an FA composition (FAC) very different from the FAC
      of the control diet. Thus, it is difficult to determine if simply reducing the
      fat content of the diet without changing the dietary FAC changes the tissue FAC
      or alters plasma lipid levels. In this study, we fed diets that contained either
      22 or 39% of calories from fat, but had no differences in their FAC, for 50 d to
      a group (n = 11) of healthy men (20-35 y). Thus, the polyunsaturated/saturated
      ratios (1.0) of the diets were identical as were the n-3/n-6 ratio and the
      monounsaturated-to-total fat ratios. The diets contained (wt% of total fat)
      approximately 28% saturated FA, 33% monounsaturated cis-FA, 6% monounsaturated
      trans-FA, 22% n-6 polyunsaturated FA, and 7% n-3 polyunsaturated FA, and 4% other
      minor FA. The diets consisted of natural foods and were formulated to contain 16
      en% protein, either 45 or 62 en% carbohydrate (CHO) and at least the recommended
      daily allowance for all micronutrients. Both diets contained 360 mg of
      cholesterol per day. All subjects were given the HF diet for 20 d, and then six
      were placed on the LF and the other five remained on the HF diet for 50 d. The
      two groups were crossed-over for the remaining 50 d of the study. The subjects'
      baseline total cholesterol level was 173 mg/dl, after 50 d on the HF diet it was
      177 mg/dl and after 50 d on the LF diet, 173 mg/dl. The differences were not
      significant, and there were no significant changes in either the LDL or HDL
      cholesterol levels with either diet. Triglyceride levels, and consequently very
      low density lipoprotein levels, rose significantly on the LF, higher CHO diet
      compared to the levels found in the subjects on the HF diet (91.5 and 66.4 mg/dl
      respectively, P < 0.002). The linoleic acid content of the plasma, platelets, and
      red blood cells was significantly (P < 0.05) reduced in the LF diet compared to
      HF diet, without any obvious physiological effects. Hence, many earlier
      observations indicating reductions in plasma lipid levels when people are on LF
      diets may be due to changes in the FAC of the diet, not the reduction in fat
      calories.

PMID- 8569437
TI  - Changes in linoleic acid metabolism and membrane fatty acids of LLC-PK cells in
      culture induced by 5 alpha-cholestane-3 beta,5,6 beta-triol.
AB  - The aim of this study was to investigate the effect of the oxysterol 5 alpha
      cholestane-3 beta,5,6 beta-triol (triol) on the metabolism of linoleic acid
      (18:2n-6) to arachidonic acid (20:4n-6) and on the cell membrane fatty acid
      composition. Porcine kidney cells were incubated in medium with or without 10
      microgram(s)/mL of triol for 24 h, then incubated for 1, 6, or 12 h in a medium
      which contained 50 muM of either [14C] linoleic acid or unlabeled linoleic acid.
      The cellular uptake of [14C] linoleic acid was significantly higher in the triol
      treated cells than in control cells. After 1- and 6-h incubations despite the
      increase of [14C] linoleic acid pool size in the triol-treated cells, neither
      total n-6 polyunsaturated fatty acids (PUFA) metabolites nor arachidonic acid
      were increased in the triol-treated cells as compared to the control cells, but
      trienoic acids accumulated to a greater extent in the triol-treated cells.
      Therefore, the ratios of n-6 PUFA metabolites vs. pool size of linoleic acid and
      of tetraenoic acids vs. dienoic acids were significantly decreased in triol
      treated cells as compared to the control cells. The cellular fatty acid
      composition also showed that linoleic acid percentage was significantly increased
      while arachidonic acid percentage was significantly decreased in the triol
      treated cells, and that the accumulation of trienoic acids (18:3n-6 + 20:3n-6)
      observed from the [14C] linoleic acid experiment was due solely to increased
      20:3n-6 content. This latter finding indicates that a decrease of elongase
      activity by triol is unlikely. Our results also showed that the triol-treated
      cells had a lower level of free cholesterol but higher levels of phospholipid and
      triol in their membranes, suggesting that triol displaced free cholesterol from
      the cell membrane.

PMID- 8569438
TI  - Effects of non-beta-oxidizable sulfur-substituted fatty acid analogues on
      synthesis and secretion of triacylglycerol and cholesterol in cultured rat
      hepatocytes.
AB  - The mechanisms behind the hypolipidemic effect of two sulfur-substituted fatty
      acid analogues, 3-thiadicarboxylic acid and tetradecylthioacetic acid, have been
      investigated in cultured hepatocytes. There was a dose-dependent reduction in
      incorporation of [3H] water into triacylglycerol and diacylglycerol when
      tetradecylthioacetic acid was added to rat hepatocytes cultured in the presence
      of 200 muM oleic acid. Tetradecylthioacetic acid also increased the oxidation of
      [14C]palmitic acid compared to oleic acid, inhibited the incorporation of
      radiolabeled precursors into diacylglycerol to a greater extent than into
      triacylglycerol, and reduced the secretion of triacylglycerol more than its
      synthesis. A stimulation, rather than a reduction, in glycerolipid synthesis and
      secretion by oxidation of fatty acids and reduces the synthesis and secretion of
      glycerolipids. 3-Thiadicarboxylic acid reduces the synthesis and secretion of
      both glycerolipids and cholesterol to approximately the same extent without a
      concomitant increase in the oxidation of fatty acids.

PMID- 8569439
TI  - Enzymatic hydrolysis of long-chain N-heterocyclic fatty esters.
AB  - Incubation of a 1-pyrroline ester [viz. methyl 8-(5-hexyl-1-pyrroline-2
      yl)octanoate, 1] with bakers' yeast (Saccharomyces cerevisiae) gave the
      corresponding free fatty acid (1a, 52%). The C = N bond of the 1-pyrroline was
      not reduced by the yeast. Complete hydrolysis of compound 1 was successful using
      lipase of Candida cylindracea (CCL) or Lipolase (Rhizomucor miehei) under stirred
      or ultrasound condition. Fatty esters containing a pyrrolidine [viz. methyl 8
      (cis/trans-5-hexyl-pyrrolidine-2-)octanoate, 2] or N-methyl pyrrolidine [viz.
      methyl 8-(cis-5-hexyl-N-methyl-pyrrolidine-2-)octanoate, 3] system in the alkyl
      chain were not hydrolyzed by either CCL or Lipolase, unless conducted in an
      ultrasonic bath. The hydrolytic activities of the enzymes appeared to be strongly
      affected by the stereochemistry of the N-heterocyclic ring system. Chemical
      hydrolysis of compounds 1-3 gave the corresponding fatty acid N-HCl salts.

PMID- 8569440
TI  - Acute effects of exercise on muscle MRI in peripheral arterial occlusive disease.
AB  - The midcalf muscles of eight patients who had peripheral arterial occlusive
      disease were evaluated by exercise MRI before and after bypass surgery or
      percutaneous transluminal angioplasty. MRI showed a high intensity of these
      muscles, especially the posterior muscles, after exercise in all patients before
      intervention. The mean T2 relaxation time was maximal immediately after exercise
      (tibialis anterior, T2 = 30.8 ms; soleus, T2 = 36.2 ms; gastrocnemius, T2 = 32.8
      ms) and then gradually decreased to the preexercise level. The difference in the
      T2 relaxation time of the soleus between immediately after exercise and at rest
      was smaller along with improvement of ankle pressure indices (API) after
      successful intervention (mean T2 difference: 4.91 and 0.72 ms (p < .001); mean
      API: 0.54 and 0.86 (p < .001) before and after intervention, respectively). The
      mean resting midcalf T2 relaxation time was significantly higher after
      intervention (tibialis anterior, T2 = 28.4 and 29.5 ms (p < .05); soleus, T2 =
      31.4 and 32.9 ms (p < .05); gastrocnemius, T2 = 29.5 and 31.1 ms (p < .01) before
      and after intervention, respectively). T2 relaxation time may be a useful
      quantitative parameter in peripheral arterial occlusive disease as well as in
      other muscle studies.

PMID- 8569441
TI  - Physical and chemical properties of superparamagnetic iron oxide MR contrast
      agents: ferumoxides, ferumoxtran, ferumoxsil.
AB  - The bulk physiochemical properties of the active ingredients in three AMI
      colloidal, superparamagnetic iron oxide (SPIO), MR contrast agents are described.
      Ferrous content and X-Ray diffraction (XRD) of the colloids are consistent with
      nonstoichiometric magnetite phases in all three active ingredients. No separate
      maghemite (gamma-Fe2O3) phases were detected by XRD. XRD line-broadening
      determinations of representative samples of ferumoxides (dextran coated),
      Ferumoxtran (dextran covered), and ferumoxsil (siloxane coated) yielded mean
      crystal diameters (volume weighted distribution) of 4.8-5.6, 5.8-6.2, and 7.9-8.8
      nm, respectively. Transmission electron microscopy (TEM) showed that the crystal
      sizes were lognormally distributed with respective mean crystal diameters (number
      weighted distribution) of 4.3-4.8, 4.3-4.9, and 8.0-9.5 nm, respectively.
      Consistent with their small crystal sizes, the three SPIO colloids are
      superparamagnetic with no remanence after saturation at high applied fields (< 1
      T), and showed characteristic relaxed Mossbauer spectra. The Mossbauer spectra of
      ferumoxides and Ferumoxtran were consistent with the presence of
      superparamagnetic relaxation above a blocking temperature of approximately 60 K.
      Due to the larger crystal sizes of ferumoxsil, its Mossbauer spectra showed the
      presence of rapid collective magnetic excitations on the Mossbauer time scale
      (approximately 1-10 ns). All three colloids showed high MR relaxivities. TEM of
      the SPIO colloids showed that ferumoxides and ferumoxsil are composed of
      aggregates of nonstoichiometric magnetite crystals, while Ferumoxtran consists of
      single crystals of nonstoichiometric magnetite. Dynamic light scattering (PCS)
      measurements showed that Ferumoxtran particles have average hydrodynamic
      diameters of approximately 21 nm (number weighted distribution) or 30 nm (volume
      weighted distribution). The data indicate that Ferumoxtran crystals are coated
      with an 8-12 nm layer of dextran T-10. Ferumoxides aggregates have average
      particle sizes of approximately 35 nm (number average distribution; TEM and PCS),
      or approximately 50 nm (volume weighted distribution; PCS). Mean sizes of
      ferumoxsil aggregates are approximately 300 nm (intensity weighted distribution).
      A discussion of the various particle size distributions is presented.

PMID- 8569442
TI  - Surface properties of superparamagnetic iron oxide MR contrast agents:
      ferumoxides, ferumoxtran, ferumoxsil.
AB  - The surface properties of the active ingredients in AMI colloidal,
      superparamagnetic iron oxide magnetic resonance (MR) contrast agents are
      described. Scanning electron microscopy/energy dispersive X-ray elemental
      analyses and diffuse reflectance Fourier transform infrared spectroscopy (FTIR)
      spectra of ferumoxsil (AMI-121 drug substance) were consistent with the presence
      of a monolayer of H2NCH2CH2NHCH2CH2CH2Si(O-)3 siloxane monomer or dimer. The X
      ray photoelectron spectra (XPS) of ferumoxsil are also consistent with complete
      coverage of the iron oxide surface with a monolayer of siloxane. The static
      secondary ion mass spectra (SSIMS) of ferumoxsil showed that the siloxane film is
      covalently bonded (i.e., Si-O-Fe bonds) to the iron oxide surface. The FTIR of
      ferumoxides (AMI-25) and Ferumoxtran (AMI-227) showed only adsorbed dextran. The
      XPS spectra of the dextran-coated colloids showed that Ferumoxtran has a thicker
      layer of dextran than ferumoxides iron oxide particles (approximately 5 and
      approximately 3 nm, respectively). The SSIMS spectra of these dextran-coated
      colloids showed only low mass fragments due to the adsorbed dextran. The nature
      of the interactions of the dextran coating with the iron oxide surfaces of
      ferumoxides and Ferumoxtran is discussed.

PMID- 8569443
TI  - MRI of human tumor xenografts in vivo: proton relaxation times and extracellular
      tumor volume.
AB  - Proton T1 and T2 differ substantially between tumors, but the tumor properties
      causing heterogeneity in T1 and T2 have not been fully recognized. The purpose of
      the study reported here was to investigate whether differences in T1 and T2
      between tumors are mainly a consequence of differences in the fractional volume
      of the extracellular compartment. The study was performed using a single human
      tumor xenograft line showing large naturally occurring intratumor heterogeneity
      in the size of the extracellular compartment. The size of the extracellular
      compartment was calculated from the volume and the density of the tumor cells.
      Cell volume was measured by an electronic particle counter. Cell density was
      determined by stereological analysis of histological preparations. T1 and T2 were
      measured by MRI in vivo both in the absence and presence of Gd-DTPA. Two spin
      echo pulse sequences were used, one with a repetition time (TR) of 600 ms and
      echo times (TEs) of 20, 40, 60, and 80 ms and the other with a TR of 2,000 ms and
      TEs of 20, 40, 60, and 80 ms. Measurements of T1 and T2 in the presence of Gd
      DTPA were performed in a state of semi-equilibrium between uptake and clearance
      of Gd-DTPA. MR-images and histological preparations of tumor subregions
      homogeneous in extracellular volume were analysed in pairs. The extracellular
      volume differed between tumor subregions from 5 to 70%. T1 and T2 measured in the
      absence of Gd-DTPA differed between tumor subregions by a factor of approximately
      1.5 and increased with increasing extracellular volume. The relative decrease in
      T1 caused by Gd-DTPA, represented by (T1 control-T1 Gd-DTPA)/T1 control, also
      increased with increasing extracellular volume.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8569444
TI  - Postprocessing of functional MRI data of motor cortex stimulation measured with a
      standard 1.5 T imager.
AB  - Functional magnetic resonance imaging (fMRI) is usually based on acquisition of
      alternating series of images under rest and an activation task (stimulus). Brain
      activation maps can be generated from fMRI data sets by applying several
      mathematical methods. Two methods of image postprocessing have been compared: (i)
      simple difference of mean values between rest and stimulation, and (ii) Student's
      t-test. The comparison shows that the difference method is very sensitive to
      arbitrary signal fluctuations as seen mainly in large vessels (e.g., in the
      sagittal sinus), leading to insignificantly activated spots in brain activation
      maps. In contrary, Student's t-test maps show strongly reduced sensitivity for
      fluctuations and have the advantage of giving activation thresholds by setting
      significance levels. This allows the comparison of activation strength between
      patient collectives by using a grid overlay technique leading to an observer
      independent quantification of the stimulation effects. The method was able to
      reproduce previous findings of activation differences between healthy volunteers
      and schizophrenic patients. Moreover, a simple algorithm for the correction of
      slight head movements during the functional imaging task is presented. The
      algorithm is based on shifting the fMRI data set relative to a reference image by
      maximizing the linear correlation coefficients. This leads to a further reduction
      of insignificant brain activation and to an improvement in brain activation map
      quality.

PMID- 8569445
TI  - A combined analysis and magnetic resonance imaging technique for computerised
      automatic measurement of cartilage thickness in the distal interphalangeal joint.
AB  - It is well known that magnetic resonance imaging (MRI) contrast can be
      controlled, albeit sometimes at the expense of image resolution and signal-to
      noise ratio, and most studies of articular joints have used a single MRI
      protocol, which is optimised for subjective image analysis. Inevitably that
      single protocol frequently compromises the detection of one or another of the
      boundaries between which any measurement must be made. This paper describes an
      alternative approach in which the criteria for computerised edge detection
      necessary for fully automated measurement of cartilage thickness are used to
      define the MRI acquisition parameters. This necessitates the combined use of two
      MRI sequences, one optimised for the cartilage-bone boundary, and the other for
      cartilage-synovial fluid. This provides a highly effective combination and its
      efficacy is demonstrated for the distal interphalangeal joint of a range of
      asymptomatic adults.

PMID- 8569446
TI  - Comparison of supervised MRI segmentation methods for tumor volume determination
      during therapy.
AB  - Two different multispectral pattern recognition methods are used to segment
      magnetic resonance images (MRI) of the brain for quantitative estimation of tumor
      volume and volume changes with therapy. A supervised k-nearest neighbor (kNN)
      rule and a semi-supervised fuzzy c-means (SFCM) method are used to segment MRI
      slice data. Tumor volumes as determined by the kNN and SFCM segmentation methods
      are compared with two reference methods, based on image grey scale, as a basis
      for an estimation of ground truth, namely: (a) a commonly used seed growing
      method that is applied to the contrast enhanced T1-weighted image, and (b) a
      manual segmentation method using a custom-designed graphical user interface
      applied to the same raw image (T1-weighted) dataset. Emphasis is placed on
      measurement of intra and inter observer reproducibility using the proposed
      methods. Intra- and interobserver variation for the kNN method was 9% and 5%,
      respectively. The results for the SFCM method was a little better at 6% and 4%,
      respectively. For the seed growing method, the intra-observer variation was 6%
      and the interobserver variation was 17%, significantly larger when compared with
      the multispectral methods. The absolute tumor volume determined by the
      multispectral segmentation methods was consistently smaller than that observed
      for the reference methods. The results of this study are found to be very patient
      case-dependent. The results for SFCM suggest that it should be useful for
      relative measurements of tumor volume during therapy, but further studies are
      required. This work demonstrates the need for minimally supervised or
      unsupervised methods for tumor volume measurements.

PMID- 8569447
TI  - Quantitative magnetic resonance flow and diffusion imaging in porous media.
AB  - Quantitative flow and diffusion measurements have been made for water in model
      porous media, using magnetic resonance micro-imaging methods. The samples
      consisted of compacted glass beads of various sizes down to 1 mm diameter.
      Typical flow and diffusion images exhibited a spatial resolution of 117 microns x
      117 microns and velocities in the range 1-2 mm/s. Comparison of volume flow rates
      calculated from the flow velocity maps with values measured directly yielded good
      agreement in all cases. There was also good agreement between the mean diffusion
      coefficient of water calculated from the diffusion maps and the bulk diffusion
      coefficient for pure water at the same temperature. In addition, the mean
      diffusion coefficient did not depend on the pore sizes in the bead diameter range
      of 1-3 mm. Our results also show that partial volume effects can be compensated
      by appropriate thresholding of the images prior to the final Fourier
      transformation in the flow-encoding dimension.

PMID- 8569448
TI  - Aging of polymer networks as studied by material property NMR imaging.
AB  - Relaxation-weighted NMR imaging is a powerful tool for the investigation of aging
      processes in rubber networks, in particular if it is combined with a theoretical
      description to relate the NMR data with suitable parameters of the material.
      Following this concept, spin-spin relaxation decays in rubber samples, consisting
      of differently aged pieces of natural rubber have been acquired in a spatially
      resolved experiment. The data were evaluated using a dynamical model and
      transformed into images of those material properties, which are affected by the
      aging process. Images representing the crosslink density and the correlation
      times, which characterize the polymer chain dynamics, have been calculated. The
      differently aged rubber pieces can be easily discriminated in such material
      property (MAP) images.

PMID- 8569449
TI  - Diffusion of cell-associated water in ripening barley seeds.
AB  - Diffusion rate and restricted diffusion of cell-associated water in ripening
      barley seeds were examined by NMR microscopy using the pulse gradient spin-echo
      and the pulse gradient stimulated-echo methods. Changes in the mobility of cell
      associated water and properties of cell membranes during ontogeny seed were
      assessed. Diffusion coefficients for bulk water transfer were high (greater than
      0.9 x 10(-5) cm2/s) throughout the growth stages. The highest diffusion
      coefficient observed was comparable to the self-diffusion coefficient of pure
      water. Water compartment sizes and the permeability of the cell membranes in the
      seed were determined by Meerwall and Ferguson's modification of the model of
      Tanner or by the method of Callaghan et al. The endosperm consisted of large
      cells and vascular bundle small cells with permeable membranes.

PMID- 8569450
TI  - Parametric multiecho proton spectroscopic imaging: application to the rat brain
      in vivo.
AB  - A parametric multiecho variant of proton spectroscopic imaging (SI) is presented
      using a multiecho SI sequence with uniform phase-encoding of all echoes within
      each echo train. The acquisition of SI data sets at different echo times (TE)
      increases the amount of information obtained within the same total measuring time
      as in standard SI measurements. The gain in information can be used: (a) to
      choose the most appropriate TE for each metabolite signal with respect to T2,
      spin coupling, or problems caused by peak overlap; (b) to measure the relaxation
      time T2 of metabolite signals with high spatial resolution; or (c) to improve the
      signal-to-noise ratio for metabolite signals with long T2 values by adding
      spectra calculated from consecutive echoes. The method was tested in vivo on
      healthy rat brain and applied to study metabolic changes in rat brain lesions.

PMID- 8569451
TI  - Choice of soft pulse shapes for signal excitation in chemical shift selective
      imaging.
AB  - The choice of soft pulse shapes for chemical shift selective excitation in
      chemical shift imaging is discussed. In the presence of inhomogeneities in the
      static magnetic field resulting from susceptibility anomalies, it is important to
      optimise pulse bandshape and frequency offset as well as bandwidth, in order to
      minimize artefacts arising from excitation of unwanted resonances. A comparison
      of the use of Gaussian and sinc shaped excitation pulses in the chemical shift
      micro-imaging of grapes serves to illustrate some of the effects that may be
      observed.

PMID- 8569452
TI  - Proteinase inhibitors from the European medicinal leech Hirudo medicinalis:
      structural, functional and biomedical aspects.

PMID- 8569453
TI  - Future doc 2025.

PMID- 8569454
TI  - Prevalence of psychiatric disorder alone versus substance abuse/dependence in a
      Baltimore City public psychiatric hospital.

PMID- 8569455
TI  - Programs need to educate youth about drugs, sex, and HIV.

PMID- 8569456
TI  - More on women in organized medicine.

PMID- 8569457
TI  - Factors affecting influenza vaccination among attendees at a senior center.
AB  - Influenza is an important cause of morbidity and mortality in the elderly. We
      questioned attendees at a Baltimore County senior center that offered influenza
      vaccination about the factors that influenced their decision to receive
      vaccination. Of the 43 responders, 37 (86%) stated they already had received
      vaccination in 1994 or were planning to be vaccinated. Vaccinated seniors were
      more likely than nonvaccinated seniors to believe that they were susceptible to
      influenza and they were more likely to have had influenza vaccination recommended
      to them by their physician. Vaccinated seniors also were more knowledgeable about
      the influenza vaccine. Physician recommendation appears to be an important factor
      in the decision by seniors to receive influenza vaccination.

PMID- 8569458
TI  - Oral morphine protocol for sickle cell crisis pain.
AB  - The painful vaso-occlusive crises that complicate sickle cell anemia can be
      difficult and frustrating for both patient and physician. We describe our
      experience using an oral morphine protocol for the treatment of sickle cell
      crisis pain. The emergency department (ED) visits of nine patients with sickle
      pain were reviewed for the 12 months before and after implementation of the
      protocol. The oral morphine regimen was associated with a significant reduction
      in the number of ED visits, total number of hours spent in the ED, and the
      proportion of visits that ended in admission to hospital (P < 0.01). The protocol
      is a useful tool for providing consistent oral analgesia to patients with sickle
      crisis pain.

PMID- 8569459
TI  - A 36-year-old woman with altered sensorium.

PMID- 8569461
TI  - The Baltimore Rh Typing Laboratory: fifty years of service.

PMID- 8569460
TI  - Case report: paclitaxel-induced myocardial ischemia.

PMID- 8569462
TI  - Samuel Baker, M.D., founder of the Med Chi library.

PMID- 8569463
TI  - Computer-based education in mental health.

PMID- 8569464
TI  - Development of a knowledge-based electronic patient record.
AB  - To help clinicians care for patients with HIV infection, we developed an
      interactive knowledge-based electronic patient record that integrates rule-based
      decision support and full-text information retrieval with an online patient
      record. This highly interactive clinical workstation now allows the clinicians at
      a large primary care practice (30,000 ambulatory visits per year) to use online
      information resources and fully electronic patient records during all patient
      encounters. The resulting practice database is continually updated with outcome
      data on a cohort of 700 patients with HIV infection. As a byproduct of this
      integrated system, we have developed improved statistical methods to measure the
      effects of electronic alerts and reminders.

PMID- 8569465
TI  - A relational model for automated health maintenance screening.

PMID- 8569466
TI  - The long QT syndrome. A review of recent molecular genetic and physiologic
      discoveries.
AB  - There is great reason for optimism in the field of research into the long QT
      syndrome (LQT). We have made considerable progress, but there is much more to be
      done. We used molecular genetics to identify genes responsible for 2 forms of LQT
      (cardiac potassium and sodium channel genes HERG and SCN5A, respectively). These
      discoveries have led to improved mechanistic undertaking of the disorder and
      created the possibility for genetic testing. We are working to develop genetic
      tests for autosomal dominant LQT, but this will require identification of
      additional LQT genes. Specialized research laboratories like ours can provide
      genetic testing for many families, but these tests are not yet generally
      available. These tests may be particularly useful for families with LQT, since
      asymptomatic LQT gene carriers are still at risk for sudden death. Finally,
      molecular genetic and physiologic studies offer the possibility of new strategies
      for treatment and prevention of this cardiovascular disease.

PMID- 8569467
TI  - Prognostic factors in polyarteritis nodosa and Churg-Strauss syndrome. A
      prospective study in 342 patients.
AB  - We undertook this study to determine the clinical, biologic, immunologic, and
      therapeutic factors associated with the prognoses of polyarteritis nodosa (PAN)
      and Churg-Strauss syndrome (CSS). Three hundred forty-two patients (260 with PAN,
      82 with CSS) followed from 1980 to 1993 were included in a prospective study on
      prognostic factors. Two hundred eighty-eight of these patients were included in
      the prospective studies on PAN and CSS. Items to be considered for analysis were
      collected at the time of diagnosis, during the acute phase of the disease. A
      survival curve was plotted for each clinical and biologic symptom observed in PAN
      or CSS. Each treatment arm of the prospective therapeutic trials was also tested:
      1) prednisone (CS) + oral cyclophosphamide (CYC) + plasma exchanges (PE) versus
      CS E, 2) CS + PE versus CS, 3) CS + oral CY versus CS + pulse CY, 4) CS + pulse
      CY + PE versus CS + pulse CY in severe PAN and CSS, and 5) PE + antiviral agents
      after short-term CS in hepatitis B virus-related PAN. Of the parameters thus
      evaluated, the following had significant prognostic value and were responsible
      for higher mortality: proteinuria > 1 g/d (p < 0.0001; relative risk [RR] 3.6),
      renal insufficiency with serum creatinine > 1.58 mg/DL (p < 0.02; RR 1.86), GI
      tract involvement (p < 0.008. RR 2.83 for surgery). Cardiomyopathy and CNS
      involvement were associated with a RR of mortality of 2.18 and 1.76,
      respectively; these were not statistically significant. Similar survival rates
      were obtained with the prospectively tested therapies. The five-factors score
      (FFS) we established considered the prognostic factors creatinemia, proteinuria,
      cardiomyopathy, GI tract involvement, and CNS signs. Multivariate analysis showed
      that proteinuria (due to vascular or glomerular disease) and GI tract involvement
      were independent prognostic factors. When FFS = 0 (none of the 5 prognostic
      factors present), mortality at 5 years was 11.9%; when FFS = 1 (1 of the 5
      factors present), mortality was 25.9% (p < 0.005); when FFS > 2 (3 or more of the
      5 factors present), mortality was 45.95% (p < 0.0001 between 0 and 2, p < 0.05
      between 1 and 2). We conclude that an initial assessment of PAN or CSS severity
      enables outcome and mortality to be predicted. The FFS is a good predictor of
      death and can be used to help the clinician choose the most adequate treatment.
      Renal and GI signs are the most serious prognostic factors.

PMID- 8569469
TI  - The autopsy. An antidote to misdiagnosis.

PMID- 8569468
TI  - Misdiagnosis at a university hospital in 4 medical eras.
AB  - In the present study 100 randomly selected autopsies from each of the years 1959,
      1969, 1979, and 1989 at a German university hospital were analyzed to determine
      whether advances in diagnostic procedures have reduced the misdiagnosis rate. We
      define misdiagnosis as occurring when a disease that does not exist is assumed to
      be present and when the failure to recognize the true existing disease leads to a
      worsened patient prognosis. In all years analyzed, about 10% of the autopsies
      revealed a misdiagnosis; another 25% disclosed a false negative diagnosis; which
      did not influence the patient's prognosis; and about 10% disclosed a false
      positive diagnosis, which again did not influence the patients prognosis. The
      most common diagnostic errors were pulmonary emboli, myocardial infarctions,
      neoplasms, and infections. The introduction of new diagnostic procedures such as
      ultrasound, computerized tomography, and radionuclide scans has not reduced the
      rate of misdiagnoses. Misinterpretation, technical errors, and overreliance on
      these new procedures occasionally contributed directly to diagnostic errors. By
      contrast, the patient's medical history and physical examination played an
      important role in the diagnostic process, leading to a correct final diagnosis in
      60%-70% of cases.

PMID- 8569470
TI  - The fasciitis-panniculitis syndromes. Clinical and pathologic features.
AB  - The authors propose to encompass under the designation of "fasciitis-panniculitis
      syndromes" (FPS) a group of disorders characterized by induration of the skin due
      to chronic inflammation and fibrosis of the subcutaneous septa and muscular
      fascia. The prototype of the FPS is eosinophilic fasciitis. Thirty-two
      consecutive patients with FPS were cared for at the author's hospital during a 10
      year period. The association of the FPS with other diseases, clinical
      presentations, histologic features, and response to treatment were analyzed.
      Idiopathic FPS, that is, eosinophilic fasciitis, was diagnosed in 14 patients. In
      the remaining 18 cases, the FPS were ascribed to vascular disorders (n = 6),
      infections (n = 6), and neoplastic disorders (n = 3), while trauma, insect bites,
      and Sweet syndrome antedated the FPS in 1 patient each. The lesions had a sleeve
      like distribution in 20 patients, plaque-like distribution in 7, and a combined
      pattern in 5. Skin biopsies revealed lesions in the deep subcutaneous layers with
      the pathologic triad of septal and fascial fibrosis, chronic inflammatory
      infiltration, and small-vessel vasculopathy. Spontaneous improvement occurred in
      4 cases. Following cimetidine monotherapy, complete remission was achieved in an
      additional 3 of 5 patients. The concept of the FPS serves to advance our
      understanding on several fronts: emphasizing the clinical and etiologic
      diversity; recognizing a stereotypic tissue reaction pattern; highlighting the
      panniculitis in addition to the fasciitic component; and describing a similar
      response to drug therapy in different clinical settings. Based on the results of
      the present series, cimetidine may be recommended as first-line treatment.

PMID- 8569471
TI  - Preliminary survey of phlebotomine sandflies (Diptera: Psychodidae) in northern
      Nigeria.

PMID- 8569472
TI  - High prevalence of malaria in a village of the Colombian Pacific coast.

PMID- 8569473
TI  - The use and mis-use of some ecological terms and concepts in epidemiology.
AB  - The article discusses the current use and mis-use of ecological terms and
      concepts in epidemiological literature, and in special, in works dealing with
      zoonotic diseases. A selection of examples was taken from papers recently
      published on the transmission of Chagas' disease by Triatoma sordida. Proper
      definitions are listed, with the intent of helping non-ecologists to use those
      terms and concepts correctly.

PMID- 8569474
TI  - Cercarial emergence of Schistosoma mansoni from Biomphalaria glabrata and
      Biomphalaria straminea.

PMID- 8569475
TI  - Ultrastructural aspects of spermatogenesis in Metamicrocotyla macracantha
      (Alexander, 1954) Koratha, 1955 (Monogenea; Microcotylidae).
AB  - Ultrastructural aspects of spermatogenesis, spermiogenesis and of the mature
      spermatozoon of a microcotylid monogenean Metamicrocotyla macracantha parasite
      from Mugil liza, are described. The irregularly-shaped spermatogonia divides by
      successive mitoses, forming the primary spermatocytes, identified by the presence
      of synaptonemal complexes in their nuclei. The spermatids formed by meiotic cell
      divisions of the secondary spermatocytes, differentiate into a mature
      spermatozoon. Cross sections of the head and the middle region of mature
      spermatozoa show the nucleus with strong condensed chromatin, the mitochondria
      with short cristae, peripheral microtubules and two axonemes with a 9 + 1
      pattern, confirming the characteristics of this genus.

PMID- 8569476
TI  - Presence of Strongyluris-like larvae (Nematoda) in some terrestrial molluscs in
      Brazil.

PMID- 8569477
TI  - Low occurrence of arthritic manifestations in patients with pulmonary
      tuberculosis. T cell subsets and humoral studies.
AB  - Given the suspected role of mycobacteria in the establishment of disorders with
      an autoimmune background and joint damage, a study was conducted to analyze
      whether rheumatic symptoms were likely to be present in tuberculosis (TB)
      patients. To this end, 330 patients with a bacteriologic confirmation of
      tuberculosis were investigated for the presence of arthritic complaints. The
      latter were recorded in five of them with rheumatic symptoms mostly involving
      interphalangeal and metacarpophalangeal joints, and preceding the clinical
      manifestations of the TB illness. Three out of these five patients remained
      arthritic by the time of the bacteriologic conversion and fulfilled the criteria
      for the diagnosis of rheumatoid arthritis. In the two remaining patients sputum
      negativization was accompanied by a disappearance of rheumatic manifestations.
      These patients were also assessed for their peripheral levels of major T cell
      subsets as well as for the presence of autoantibodies. Comparisons with a series
      of non-arthritic TB cases, rheumatoid arthritis patients, and controls revealed
      that presence of rheumatic manifestations was associated with a different profile
      of autoantibody formation and T cell subset changes. Evidence recorded in the
      present study indicates that joint affectation in TB is a rare event, being
      rather the exception than the rule.

PMID- 8569478
TI  - Toxigenic and invasive capacities: possible pathogenic mechanisms in Arcobacter
      cryaerophilus.

PMID- 8569479
TI  - Eurytrema coelomaticum: influence of the infection on the reproduction and
      nucleic acids contents in the albumen gland and ovotestis of Bradybaena
      similaris.
AB  - The number of eggs laid per snail in Bradybaena similaris and the nucleic acids
      (DNA and RNA) in the albumen gland and ovotestis were quantified in snails
      infected with sporocysts of the digenetic trematode Eurytrema coelomaticum. The
      total number of eggs laid per mollusc was reduced by 96.32% at the end of the
      larval development. The DNA concentration increased by 700%, and the RNA
      concentration was reduced by 8.38% by the time when the daughter sporocysts of E.
      coelomaticum were released from B. similaris. The relation between these values
      and the inhibition of the reproduction observed in infected molluscs is
      discussed.

PMID- 8569480
TI  - Daily pattern of flight activity of Aedes albifasciatus in central Argentina.
AB  - Aedes albifasciatus is an important common mosquito in Central Argentina. It is a
      confirmed vector of the Western Equine Encephalitis and is responsible for loss
      of milk production in dairy cattle during peak populations. This paper reports
      the flight activity pattern of Ae. albifasciatus for different seasons, in the
      southern coast of the Mar Chiquita Lake (central Argentina). Data were collected
      by sampling two sites between 1992 and 1993 with CDC traps and human-bait
      captures. Adult mosquito population density, estimated by CDC trapping and human
      bait, were highly correlated. However, when compared to other species, the
      proportion of Ae. albifasciatus was higher in human-bait collections. Adult
      female populations were active only when temperature were higher than 6 degrees
      C. Two daily biting peaks were observed (dusk and dawn) during the spring, summer
      and autumn, and only one peak during winter (around 15:00 pm). Adult abundance
      was significantly correlated (R2 = 0.71; p < 0.01) with temperature and
      illumination.

PMID- 8569481
TI  - Existence of a sex pheromone in Triatoma infestans (Hemiptera: Reduviidae): I.
      Behavioural evidence.
AB  - Assembling behaviour associated with mating was investigated in Triatoma
      infestans. The spatial distribution of both sexes was observed by video films, in
      the presence or absence of a copulating pair. Males aggregated around copulating
      pairs. Females did not exhibit this behaviour and their mean spatial density
      remained unaffected. Spontaneous aggregation tendency was observed in males in
      the absence of a copulating pair, but the temporal course significantly differed
      from that observed in the presence of a mating pair. Results support the
      existence of an aggregation signal that is released during mating, affecting the
      behaviour of males.

PMID- 8569482
TI  - Existence of a sex pheromone in Triatoma infestans (Hemiptera: Reduviidae): II.
      Electrophysiological correlates.
AB  - The stimulus provided by a copulating pair of Triatoma infestans significantly
      affects the electrical activity of the nervous system of Triatoma infestans.
      Electrophysiological recordings were performed on stationary adult males
      presented with stimuli of an air current carrying odors from males, females, non
      copulating pairs and mating pairs. The electrophysiological response was
      characterized by the low frequency occurrence of biphasic compound impulses. A
      significant increase in the frequency of the impulses occurred in stationary
      males when exposed to air currents of mating pairs, when compared to that evoked
      by a clean air stream. Analysis of the time course of the assays, showed that the
      electrophysiological activity during the copula was higher than prior to or after
      copula. The electrophysiological evidence presented here strongly supports the
      existence of pheromone(s) released by one or both sexes during mating and which
      is perceived by male chemoreceptors located on the antennae.

PMID- 8569483
TI  - An erythrocytic virus of the Brazilian tree-frog, Phrynohyas venulosa.
AB  - Blood erythrocytes of Brazilian tree-frogs, Phrynohyas venulosa were found to
      frequently contain single, small, densely staining inclusions. Electron
      microscopy showed these to be icosahedral viral particles which measured from 250
      280 nm in diameter: they were devoid of an envelope, and thus differed from
      previously described viruses of frog erythrocytes. The infected erythrocytes
      lacked a crystalline body.

PMID- 8569484
TI  - [Biology of Triatoma nitida Usinger, 1939 in laboratory conditions (Hemiptera:
      Reduviidae)].
AB  - Triatoma nitida is a wild species occurring in Mexico and Central America. In
      order to establish the length of its life cycle and transmission potential, the
      following parameters were observed: the incubation period, the interval between
      hatching, or moulting, and the first feeding; the number of blood meals and the
      time of development. The time-lapse before the bite, the length of feeding and
      the interval between the end of the blood meal and defecation, as well as the
      site of defecation were also analyzed. Average length of the egg incubation
      period was 18.2 days. Time interval between the food source offering and the bite
      was less than 4 min in 60% of the analyzed cases, except in the fifth instar,
      where only 38% of the insects began feeding in less than 5 min. The blood-sucking
      period was long and rising until the fifth instar, decreasing in adults, and
      ranging from 1 min to 2 and a half hours. Only 26% of the blood meals were
      followed by defecations within 20 min. The average length of the life cycle was
      897.5 days.

PMID- 8569485
TI  - Relationships and social support: views of parents with mental
      retardation/intellectual disability.
AB  - From the professional perspective, parenting by people with mental retardation,
      or intellectual disability, is regarded with concern. Little attention has been
      paid to what constitutes social support for these parents. A qualitative design
      was used to explore views of parents with intellectual disability about their
      relationships and social support for their parenting. Most emphasis was placed on
      the support received from and given to their spouses or partners. Support was not
      always viewed as beneficial; rather, it was sometimes viewed as a restraint as
      well as a resource for parenting. Parents also exhibited a preferred sequence in
      seeking help, beginning with their partners, then family members, and, finally,
      professionals. Implications in light of policy and service provision were
      discussed.

PMID- 8569486
TI  - An evaluation of care coordination in controlling inpatient hospital utilization
      of people with developmental disabilities.
AB  - All admissions of people with developmental disabilities to a community hospital
      over 3 years were examined to evaluate the impact of a coordinated care model on
      length of stay and hospital charges. Admissions were divided into two groups,
      those receiving either coordinated care (program group) or routine care by
      community physicians (usual care group). The program group had shorter average
      lengths of stay and lower hospital charges than did the usual care group,
      especially when charges were adjusted for case mix. Similarity of severity across
      the groups was measured by number of discharge diagnoses and Medicaid case
      weights. Over the 3 years, for the 115 admissions in the program group, these
      differences amounted to more than $200,000 in potentially unnecessary hospital
      charges. Implications of care coordination services for community-based health
      care planning were presented.

PMID- 8569487
TI  - Antiepileptic drug behavioral side effects in individuals with mental retardation
      and the use of behavioral measurement techniques.
AB  - Measurement methods from behavioral psychology were used to assess antiepileptic
      drug behavioral side effects in 5 individuals with mental retardation. When the
      suspected antiepileptic drug was altered, an 81% reduction of maladaptive
      behaviors occurred. Quality of life outcomes included successful community
      placement and termination of an aversive intervention procedure. Three cases
      demonstrated antiepileptic drug exacerbation of disruptive vocalizations,
      agitation, self-injurious behavior, and property destruction; 2 demonstrated
      improved aggression, but illustrated a common clinical problem. When seizure
      control must be maintained and a suspected antiepileptic drug cannot be reduced
      before a second antiepileptic drug with potential psychotropic properties is
      initiated, it was not possible to absolutely conclude that the first
      antiepileptic drug was responsible for the behavior problem. Overall, these
      measurement methods were instrumental in the systematic clinical evaluation of
      antiepileptic drug behavioral side effects in individuals unable to verbally
      communicate the presence of these side effects.

PMID- 8569488
TI  - Factors contributing to the stability of social relationships between individuals
      with mental retardation and other community members.
AB  - Stability of social relationships may be an important indicator of lifestyle
      quality. Fourteen community members identified as being in long-term, socially
      stable relationships with one or more individuals with mental retardation
      provided answers to a quantitatively oriented questionnaire and participated in a
      more open-ended qualitative interview. In general, results indicated that the
      stability of the relationships was influenced by (a) the community members having
      previously served as staff members to the individuals with mental retardation,
      (b) their willingness to overcome logistical barriers that might otherwise have
      impeded their friendships, (c) their perception that the relationships included
      reciprocal social support, and (d) other idiosyncratic variables.

PMID- 8569489
TI  - Presidential address 1995--the shifting paradigm--from rhetoric to reality.

PMID- 8569491
TI  - Common sense is alive and well: comments on Erb (1995)

PMID- 8569490
TI  - Commentary on Erb's (1995) "where, oh, where, has common sense gone"?

PMID- 8569492
TI  - Structure determination and analysis of local bending in an A-tract DNA duplex:
      comparison of results from crystallography, nuclear magnetic resonance, and
      molecular dynamics simulation on d(CGCAAAAATGCG).
AB  - We have presented a detailed analysis for structure determinations for the DNA
      duplex d(CGCAAAAATGCG) obtained from X-ray crystallography, nuclear magnetic
      resonance, and molecular dynamics simulation. Each of the structures for the
      duplex deviates from the structure of the canonical form of B-DNA in a number of
      observable characteristics. Specifically, the three determinations all contain
      DNA axis deflections at the junctions of the A-tract with the flanking sequences.
      The analysis provided shows that the general characteristics of the structures
      obtained for d(CGCAAAAATGCG) from X-ray, NMR, and MD methods turn out to be quite
      similar. The extent to which this result can be generalized remains to be
      established by consideration of similar cross-comparisons on diverse
      oligonucleotide structures.

PMID- 8569493
TI  - DNA mismatches and modified bases.

PMID- 8569494
TI  - NMR studies of complex DNA structures: the Holliday junction intermediate in
      genetic recombination.

PMID- 8569495
TI  - Structural studies of DNA three-way junctions.

PMID- 8569496
TI  - Parallel-stranded duplex DNA: an NMR perspective.

PMID- 8569497
TI  - 1H NMR spectroscopy of DNA triplexes and quadruplexes.

PMID- 8569498
TI  - Solid-state NMR of DNA.

PMID- 8569499
TI  - Systems for the NMR study of modified nucleoside-dependent, metal-ion induced
      conformational changes in nucleic acids.

PMID- 8569500
TI  - How to generate accurate solution structures of double-helical nucleic acid
      fragments using nuclear magnetic resonance and restrained molecular dynamics.

PMID- 8569501
TI  - Preparation of isotopically enriched RNAs for heteronuclear NMR.

PMID- 8569502
TI  - Biochemical and NMR studies of RNA conformation with an emphasis on RNA
      pseudoknots.

PMID- 8569503
TI  - Multidimensional heteronuclear NMR experiments for structure determination of
      isotopically labeled RNA.

PMID- 8569504
TI  - Studies of base pair kinetics by NMR measurement of proton exchange.

PMID- 8569505
TI  - Determination of fast dynamics of nucleic acids by NMR.
AB  - Double-stranded oligonucleotides of < 10 base pairs are adequately described as
      an isotropic rotor, using the correlation time for the cytosine H6-H5 vector. For
      longer fragments, the cylindrical model should be used for detailed analysis of
      NOEs. The appropriate correlation times can be calculated using the formulae of
      Tirado and Garcia de la Torre or derived from measurements of the cross
      relaxation rate constants for cytosine (or uridine) H6-H5. Order parameters
      describing the degree of motion of different vectors on the subnanosecond time
      scale vary substantially, with typical values of S2 > 0.8 for base vectors and
      0.5-0.8 for intrasugar and base-sugar vectors. Order parameters for terminal
      nucleotides are typically significantly smaller than for internal nucleotides,
      which may also mean that their conformation will be less well determined in the
      formalism of a unique structure. The CSA relaxation rates of the phosphodiesters
      appear to be insensitive to internal motions and may, therefore, provide the most
      accurate estimate of the overall tumbling time in nucleic acid fragments. Using a
      combination of relaxation data for different nuclei and different spectrometer
      frequencies may be expected to yield detailed information about fast motions in
      nucleic acid fragments.

PMID- 8569506
TI  - Isotope labeling for 13C relaxation measurements on RNA.

PMID- 8569507
TI  - Comparison of X-ray and NMR-determined nucleic acid structures.

PMID- 8569508
TI  - Site-specific dynamics in DNA: theory and experiment.

PMID- 8569509
TI  - NMR and nucleic acid-protein interactions: the lac repressor-operator system.

PMID- 8569511
TI  - Uses of 13C- and 15N-labeled RNA in NMR of RNA-protein complexes.
AB  - The interactions between RNA and protein will not be simple ones in the sense
      that they cannot be predicted by the structure of the free RNA. The assumption in
      describing these interactions must be that the RNA nucleotide is free to use any
      or all of its chemical moieties to anchor it to the protein, and the
      spectroscopist must be ready for these possibilities. The incorporation of both
      15N and 13C into the RNA is absolutely necessary to obtain a picture of how the
      RNA is associated to the protein, and the implementation of pulsed field
      gradients allows observation of the critical hydrogen bonding sites. We must note
      here that since some of the hydrogen bonds between RNA and protein are certain to
      be mediated by water molecules, gradients should also provide a means to look for
      these specific associations.

PMID- 8569510
TI  - Induced structural changes in protein-DNA complexes.

PMID- 8569512
TI  - Studies of nucleic acids and their protein interactions by 19F NMR.

PMID- 8569513
TI  - NMR studies of drug-DNA complexes.
AB  - The application of high-resolution, multidimensional NMR techniques to the
      problem of determining the structure of drug-DNA complexes in solution has led to
      substantial progress in understanding the effect of drugs on DNA at the molecular
      level. With the development of isotopic labeling methods applied in three- and
      four-dimensional experiments, we anticipate that more complex drug-DNA systems
      will become amenable to structural analysis. In addition to implementing these
      newer techniques, progress will also be made in terms of investigating the
      structure of drug complexes with more unusual forms of DNA, such as triplexes,
      quadruplexes, multistranded junctions, and so forth.

PMID- 8569514
TI  - Distance geometry in NMR determination of solution conformation of nucleic acids:
      application of d-ACCGTTAACGGT.

PMID- 8569515
TI  - Statistical analysis of DNA duplex structural features.

PMID- 8569516
TI  - Women's right and Safe Motherhood.

PMID- 8569517
TI  - Satisfaction and continuity of care: staff views of care in a midwife-managed
      delivery unit.
AB  - OBJECTIVE: to examine whether there are differences in the midwife's role in, and
      satisfaction with, intrapartum care and delivery of women at low obstetric risk
      in a midwife-managed delivery unit compared to a consultant-led labour ward.
      DESIGN: a pragmatic randomised controlled trial. Subjects were randomised in a
      2:1 ratio between the midwives' unit and the labour ward. SETTING: Aberdeen
      Maternity Hospital, Grampian, UK. SUBJECTS: midwives within the delivery suite
      who cared for the 2844 women at low obstetric risk receiving care in a pragmatic
      randomised controlled trial of the two delivery areas. PRIMARY OUTCOME MEASURES:
      continuity of carer and midwife satisfaction. FINDINGS: midwives looking after
      women in the midwives' unit group were significantly more likely to be of a
      higher grade, more qualified and have a longer length of experience than those in
      the labour ward group. There was greater continuity of carer both during labour
      and after delivery in the midwives' unit group. Despite a small but statistically
      significant difference in overall satisfaction between the groups, area of
      'booking' or area of delivery were not important in predicting midwife
      satisfaction. Autonomy and continuity of carer were the best predictors of
      midwife satisfaction. CONCLUSIONS: midwife-managed intrapartum care increases
      continuity of carer and, therefore, midwife satisfaction. Extending this outside
      the delivery suite requires a system of care that is acceptable to midwives as
      well as women. Such systems will depend to a large extent on geography, consumer
      demand and availability of resources. However, midwife satisfaction should also
      be considered. In order to do this further research is required to fully evaluate
      the effect these systems have on the midwives working in them.

PMID- 8569518
TI  - Is measuring postnatal symphysis-fundal distance worthwhile?
AB  - OBJECTIVE: to assess levels of intra-observer and inter-observer variability in
      the measurement of postnatal symphysis-fundal distance and establish whether the
      measurement is sufficiently precise for it to be of use in clinical practice.
      SETTING: a consultant obstetric maternity unit in the south of England which
      caters for approximately 6000 deliveries per annum. METHODS: in the intra
      observer study 15 midwives took repeated readings of symphysis-fundal distance on
      30 postnatal women. In the inter-observer study 13 midwives took readings of
      symphysis-fundal distances on 24 postnatal women. Repeatability coefficients (the
      variability to be expected in the change between two measurements) were
      calculated. FINDINGS: the repeatability coefficient, that is the maximum
      difference that is likely to occur, 95% of the time, for the difference between
      two measurements obtained by the same midwife on the same woman is 2.94 cm (intra
      observer study). Where measurements are obtained by different midwives on the
      same mother the repeatability coefficient is 5.01 cm (inter-observer study). In
      everyday clinical practice variability is likely to be greater than that found in
      this study. IMPLICATIONS FOR PRACTICE: the daily measurement of the postnatal
      symphysis-fundal distance with a tape measure cannot be obtained with enough
      precision to be useful in making clinical judgements and therefore should be
      discontinued. Further research is required to assess the value of routine
      palpation of the uterine fundus to assess involution during the postnatal period.

PMID- 8569519
TI  - The transition to home for mothers of healthy and initially ill newborn babies.
AB  - Mothers' difficulties with the transition of their baby from hospital to home
      have been studied for several years. An examination of a number of studies from
      the USA, Canada, and the UK has shown a remarkable similarity in the findings
      despite the demographic and cultural differences in the sample characteristics.
      It appears, then, that maternal responses to the transition to home are more tied
      to the experience than to the setting. The purpose of this paper is to place
      these findings within a framework that would provide a means for midwives and
      nurses to help mothers make this transition more comfortably and confidently than
      in the past. The framework chosen is the Transition Model as developed by Kenner
      (1988). This model suggests the problems with transition to home can be addressed
      under the following categories: 1. information needs; 2. grief; 3. parent-child
      development; 4. stress and coping; 5. social support.

PMID- 8569520
TI  - Episiotomy at the Royal Women's Hospital, Brisbane: a comparison of practices in
      1986 and 1992.
AB  - OBJECTIVE: to determine whether the incidence of perineal outcomes, including
      episiotomy, at the Royal Women's Hospital (RWH) Brisbane reflected trends
      reported in the literature. DESIGN: retrospective record review. SETTING: RWH
      Brisbane. PARTICIPANTS: 953 women who delivered vaginally at the RWH in 1986 and
      1992. MEASUREMENTS AND FINDINGS: there was a decline in the episiotomy rate from
      65% in 1986 to 36% in 1992. This was accompanied by an increase in the incidence
      of intact perinea and spontaneous perineal tears. There was no difference in the
      incidence of spontaneous third degree tears. The decline in the incidence of
      episiotomy was found when other factors, such as parity, were considered, with
      the exception of operative vaginal delivery, where no difference in the use of
      episiotomy was found. There was no significant increase in the number of babies
      with an Apgar score of < 7 at one minute of age, despite a significant reduction
      in the use of episiotomy when delivering these babies (55% in 1986 and 19% in
      1992; P < 0.001). The second stage was significantly longer in 1992 (P < 0.01).
      KEY CONCLUSIONS: the findings reflect the decline in the incidence of episiotomy
      reported in the literature. This decline in rate was accompanied by an increase
      in the length of second stage and in the incidence of both intact perinea and
      perineal tears. Lowering the incidence of episiotomy did not result in a rise in
      the rate of babies with an Apgar score of < 7 at one minute.

PMID- 8569521
TI  - Choice, continuity and control: changing midwifery, towards a sociological
      perspective.
AB  - In this paper sociological theories of the professions and the organisation of
      work are drawn on to explain current developments in the organisation of
      maternity care. Utilising the literature on the sociology of the professions and
      general trends in health policy and labour markets, possible reasons for the
      current renaissance in midwifery and some implications for midwives are
      discussed. Thus, whilst some women and midwives may be building a paradigm of
      'woman-centered' practice based on an equal partnership, for other midwives, the
      result may be a divided workforce consisting of an elite core and casualised
      periphery based on the ability to give a full-time flexible commitment to work.
      The implications of excluding those midwives who are unable to combine full-time
      work with their own domestic commitments are discussed.

PMID- 8569522
TI  - Psychosocial factors influencing teenage sexual activity, use of contraception
      and unplanned pregnancy.
AB  - OBJECTIVE: to compare teenagers who become unintentionally pregnant and teenagers
      who have never been pregnant but are using contraception on matters related to
      family/partner stability, and communication with a parent or stable sexual
      partner about sexual matters. DESIGN: survey utilising self-completed
      questionnaire. SETTING: a hospital antenatal clinic and community-based family
      planning clinic. PARTICIPANTS: 30 teenagers with an unplanned pregnancy and 31
      'never-pregnant' teenagers using contraception. FINDINGS: the two groups were
      similar on demographic factors, mean age at which sexual intercourse was first
      experienced, total number of sexual partnerships, the number of teenagers having
      a current, regular boyfriend and mean length of the interval between when the
      teenagers first started going out with their boyfriend and when first sexual
      intercourse took place. Teenagers in the family planning clinic group were more
      likely to be living with both natural parents and to be still at school or in
      higher education. The mean length of time pregnant teenagers had been going out
      with their boyfriend was longer, they were more likely to be cohabiting with him
      and to be unemployed. Participants from the antenatal clinic group communicated
      more with their mothers about sexual matters than those in the family planning
      clinic group, who were more likely to seek this information from books. The
      family planning clinic participants were more likely to discuss personal rules
      and values with friends than those in the antenatal clinic group. IMPLICATIONS
      FOR PRACTICE: to develop understanding of factors predisposing to unplanned
      pregnancy during adolescence and to implement measures to counter them, further
      studies to examine the influence of teenagers' perceptions of family
      relationships and future life prospects on contraception use and unplanned
      pregnancy were identified.

PMID- 8569523
TI  - Women of the world, from a midwife's perspective. Report of the NGO Women's
      Forum, Beijing 30 August-9 September 1995.

PMID- 8569524
TI  - Natural occurrence of mycotoxins in Fusarium infected beans.
AB  - This is the first report on the discovery of several mycotoxins in naturally
      infected mouldy navy beans (Phaseolus vulgaris L.) with distinct whitish grey to
      pink discoloration. Species of Fusarium isolated from the mouldy beans included
      F. avenaceum, F. culmorum, F. graminearum, F. moniliforme, F. oxysporum, F.
      solani and two Fusarium spp. Three types of bean samples were analysed for
      mycotoxins: (a) health beans without any apparent discoloration, (b) beans with
      pink discoloration, and (c) a mixture of beans with whitish grey and pink
      discoloration. The results indicated that diacetoxyscripenol (DAS),
      deoxynivalenol (DON), T-2 toxin (T-2) and fumonisin B1 (FB1) were present in type
      B and C samples but not in the healthy type A samples. Quantification of DAS,
      DON, and T-2 and of FB1 were achieved by gas chromatography and high performance
      liquid chromatography, respectively. The results showed that DAS, DON, T-2 and
      FB1 were not evident in the healthy samples, but in type B and type C samples,
      DAS, DON, T-2 and FB1 in the amounts of 9.2, 6.5, 5.5 and 0.5 microgram/g, and of
      3.3, 3.1, 13.5 and 1.1 micrograms/g, respectively, were detected. Further
      research is under way to determine which species of Fusarium is responsible for
      the production of specific toxins.

PMID- 8569526
TI  - Survey of urease activity in ruminal bacteria isolated from domestic and wild
      ruminants.
AB  - A total of 909 strains, including Selenomonas ruminantium, Lactobacillus sp.,
      Enterococcus sp. and Staphylococcus sp., from the rumen of 104 domestic and wild
      ruminants was used in tests for urease activity. Tests showed that 56.7% of S.
      ruminantium strains and 18.5% of lactobacilli manifested medium urease activity
      with mean values of 14.4 +/- 2.5 and 13.85 +/- 0.25 nkat ml-1, respectively. Most
      of the Enterococcus faecium (62.2%) and all of the E. faecalis isolates expressed
      urease activity with mean values of 3.9 +/- 0.05 and 4.1 +/- 0.06 nkat ml-1. E.
      malodoratus, E. solitarius, E. mundtii, Streptococcus bovis and S. uberis did not
      produce any urease. All the staphylococci screened were urease-producing strains,
      mostly with medium or low urease activity. The highest level of urease was
      measured in the rumen epithelial wall of isolates SE30 (19.7 +/- 2.71 nkat ml-1
      of rumen content), SCU32 (29.3 +/- 1.6 nkat ml-1) and also in the rumen content
      isolates EF35 (19.9 +/- 0.94 nkat ml-1) and S. ruminantium 77 (25.35 nkat ml-1).
      This survey contributes new data to existing information relating to the
      ureolytic microbial ecosystem in ruminants.

PMID- 8569525
TI  - Effect of quaternary ammonium salts and amine oxides on Pseudomonas aeruginosa.
AB  - Two quaternary ammonium salts, viz (1-methyldodecyl) trimethylammonium bromide
      (ATDBr) and tetramethylammonium bromide (TMABr), as well as two amine oxides, (1
      methyldodecyl)dimethylamine oxide (ATDNO) and trimethylamine oxide (TMANO), were
      tested for their inhibitory activity on a Pseudomonas aeruginosa strain isolated
      from nosocomial infections. Only those compounds with long alkyl chains in their
      molecules (ATDBr and ATDNO) showed antimicrobial efficacy. In subinhibitory
      concentrations both compounds inhibited incorporation of [14C]-adenine and [14C]
      leucine as precursors of macromolecular biosynthesis. Endogenous respiration of
      the cells was more sensitive to both agents than the respiration of various
      substrates. Among the virulence factors only the production of phospholipase C
      was inhibited by sub-MICs, while the activities of elastase and proteinase were
      stimulated until the inhibitory concentrations were reached. The short-chain
      analogues TMABr and TMANO did not show these effects. It is suggested that the
      production of virulence factors is affected by amphiphilic compounds due to their
      antimicrobial activity.

PMID- 8569527
TI  - Characterization of Pseudomonas paucimobilis FP2001 which forms flagella
      depending upon the presence of rhamnose in liquid medium.
AB  - A bacterial strain FP2001 isolated from the exudate of land reclaimed for
      municipal waste was identified as Pseudomonas paucimobilis. Cells of strain
      FP2001 were mobile by means of polar monotrichous flagellum, only when rhamnose
      was added as a carbon source in the liquid medium. The replacement of rhamnose by
      arabinose, galactose, glucose or xylose did not lead to the formation of
      flagella.

PMID- 8569528
TI  - Biomaterial-associated infection with Candida albicans in mice.
AB  - Candida yeasts are frequently isolated from patients with continuous ambulatory
      peritoneal dialysis peritonitis or other biomaterial-associated infections. The
      mouse model of candidal peritonitis was used to study the interaction of Candida
      cells with end-point attached heparinized polyethylene (H-PE) and with
      polymorphonuclear leukocytes (PMNs) or macrophages (M phi). Two Candida strains
      differing in cell surface hydrophobicity and in expression of fibronectin (Fn)
      binding were used for the study. Cells of both Candida strains adhered at higher
      numbers to H-PE surfaces preadsorbed with Fn or with human dialysis fluid (HDF)
      than to non-modified H-PE, supporting a role of Fn in mediating adhesion. C.
      albicans 4016 cells expressing low hydrophobicity and low binding of soluble Fn
      demonstrated stronger adhesion to PMNs than the more hydrophobic C. albicans 3248
      yeasts, which express high binding of soluble Fn. However, C. albicans 4016 cells
      were more resistant to phagocytic killing and were hardly eradicated in
      intraperitoneally infected mice. The animals depleted in PMNs by treatment with
      CY were neither able to eradicate C. albicans 3248 (rapidly eliminated by normal
      mice) nor C. albicans 4016 yeasts (with a tendency to persist in the tissues of
      normal mice).

PMID- 8569529
TI  - The release of outer membrane vesicles from the strains of enterotoxigenic
      Escherichia coli.
AB  - The clinically isolated heat labile enterotoxin (LT)-producing strains of
      Escherichia coli can be separated into two groups, namely spontaneous LT
      releasing strain and non-spontaneous LT-releasing strain, based on their
      phenotypes of spontaneous release of LT into the culture medium. The phenotype of
      spontaneous LT release was observed to correlate closely with the phenotype of
      the release of numerous small vesicles into the culture medium. Both
      morphological and biological examinations of the vesicle showed that the vesicle
      was released from the outer membrane. It can, therefore, be assumed that LT may
      be released from the cell at the time the vesicles form.

PMID- 8569530
TI  - Characterization of nontoxic-nonhemagglutinin component of the two types of
      progenitor toxin (M and L) produced by Clostridium botulinum type D CB-16.
AB  - A 9.8-kbp DNA fragment which contained a neurotoxin gene and its upstream region
      was cloned from Clostridium botulinum type D strain CB-16. Nucleotide sequencing
      of the fragment revealed that genes encoding for hemagglutinin (HA) subcomponents
      and one for a nontoxic-nonhemagglutinin (NTNH) component were located upstream of
      the neurotoxin gene. This strain produced two toxins of different molecular size
      (approximately 300 kDa and 500 kDa) which were designated as progenitor toxins (M
      and L toxins). The molecular size of the NTNH component of L toxin was
      approximately 130 kDa on SDS-PAGE and its N-terminal amino acid sequence was M-D
      I-N-D-D-L-N-I-N-S-P-V-D-N-K-N-V-V-I which agreed with that deduced from the
      nucleotide sequence. In contrast, the M toxin had a 115-kDa NTNH component whose
      N-terminal sequence was S-T-I-P-F-P-F-G-G-Y-R-E-T-N-Y-I-E, corresponding to the
      sequence from Ser141 of the deduced sequence. A 15-kDa fragment, which was found
      to be associated with an M toxin preparation, possessed the same N-terminal amino
      acid sequence as that of the 130-kDa NTNH component. Furthermore, five major
      fragments generated by limited proteolysis with V8 protease were shown to have N
      terminal amino acid sequences identical to those deduced from the nucleotide
      sequence of 130-kDa NTNH. These results indicate that the 130-kDa NTNH of the L
      toxin is cleaved at a unique site, between Thr and Ser, leading to the 115-kDa
      NTNH of the M toxin.

PMID- 8569531
TI  - Immunogenicity of the Shigella flexneri serotype Y (SFL 124) vaccine strain
      expressing cloned glucosyl transferase gene of converting bacteriophage SfX.
AB  - The glucosyl transferase gene (gtr) from bacteriophage phage X (SfX) caused
      partial conversion of serotype Y (group antigen 3, 4) to X (group antigen 7, 8)
      when introduced into a candidate vaccine strain of Shigella flexneri serotype Y
      (SFL124). The gtr gene caused conversion of O-antigens but did not eliminate the
      adsorption of the corresponding phage SfX. The hybrid strain expressing both
      group antigens 7, 8 and 3, 4 showed 75% protection when immunized guinea pigs
      were challenged with a wild-type S. flexneri serotype X strain. No protection was
      observed against serotype Y challenge, although group antigen 3, 4 was detected
      in the LPS of the hybrid strain. This suggests the importance of O-antigen
      immunity in the host defense against shigellosis.

PMID- 8569532
TI  - Overproduction, purification, and diagnostic use of the recombinant HIV-1 Gag
      proteins, the precursor protein p55 and the processed products p17, p24, and p15.
AB  - HIV-1 Gag protein precursor p55, and its processed products, p17, p24, and p15
      were overproduced in Escherichia coli and purified to near homogeneity. To study
      the antigenic properties and the potentiality as the diagnostic and prognostic
      reagents, varying amounts of the purified Gag proteins were dotted onto the
      polyvinylidene difluoride membrane and reacted with 40 sera of HIV-1-infected
      individuals (35 AC, 1 ARC, and 4 AIDS patients) and 10 sera of normal healthy
      donors. p55 reacted with 40 (100%) sera of HIV-1 carriers, while p17, p24, and
      p15 reacted with 37 (92.5%), 35 (87.5%) and 34 (85%) of the 40 sera of HIV-1
      carriers, respectively. On the whole, the reaction of p55 was especially strong
      and that of p15 was the weakest. p55 showed the strongest reaction among the four
      Gag proteins with all specimens, and it showed a positive reaction with a carrier
      serum with which none of the processed Gag proteins showed a positive reaction.
      Therefore, p55 is the most useful antigen among the four Gag proteins for
      detection of the Gag antibodies and may even be one of the most useful antigens
      for the diagnosis of HIV-1 infection.

PMID- 8569533
TI  - Anti-hepatitis A virus antibody response elicited in mice by different forms of a
      synthetic VP1 peptide.
AB  - Peptide VP1 (11-25) of the capsid of hepatitis A virus was synthesized by the
      Fmoc-polyamide solid phase method, and administered to mice in different forms:
      (1) free, (2) encapsulated in multilamellar liposomes, (3) coupled to keyhole
      limpet hemocyanin (KHL), and (4) incorporated into a tetrameric branched lysine
      core. The highest anti-VP1 peptide responses were generated by synthetic peptides
      entrapped into liposomes and coupled to KLH. No anti-HAV response was generated
      with the free peptide, while all the other forms induced both anti-HAV and HAV
      neutralizing antibodies. Maximum neutralization indices were observed in ascites
      from mice treated with liposome-entrapped and KLH peptides.

PMID- 8569534
TI  - Interference between Neisseria meningitidis and PC-KLH induced anti
      phosphorylcholine PFC responses in NZB/W autoimmune mice.
AB  - In this work, we demonstrate that the simultaneous injection of PC-KLH and
      Neisseria meningitidis-derived antigens [NMB or PC-(NMB)HI] induced in old NZB/W
      mice defective responses as does PC-KLH challenge. On the other hand, the
      simultaneous injection of both immunogenic preparations of N. meningitidis evoked
      responses similar to those shown by old mice challenged with NMB alone.
      Alteration in PC-specific PFC responses also affected hapten-free inhibition
      profiles and their heterogeneities. The increase in PC50s of anti
      phosphorylcholine PFC responses and their heterogeneities induced by certain
      antigens with aging is correlated with a decrease in T15 idiotype expression,
      suggesting that after the T15 dominant clone disappears no other clone takes
      control of the anti-PC response. These results suggest that the mechanism(s)
      involved in the regulation of T15 marker expression play an important role in the
      inability of old NZB/W mice to mount good anti-PC responses and suggest that
      regulatory mechanisms induced by PC-KLH dominate those elicited by NMB.

PMID- 8569535
TI  - Sequential involvement of NK cells and CD8+ T cells in granuloma formation of
      Rhodococcus aurantiacus-infected mice.
AB  - We investigated the effect of in vivo administration of antibodies against T-cell
      subsets and natural killer (NK) cells on endogenous gamma interferon (IFN-gamma)
      production and granuloma formation in Rhodococcus aurantiacus-infected mice. High
      titers of endogenous IFN-gamma were detected in the extracts of the livers and
      spleens during 24 hr of the infection, reaching the peak at 8 hr, and the IFN
      gamma production was reduced by in vivo administration of anti-NK 1.1 monoclonal
      antibody (MAb) or antibody against asialo GM1+ cells. Endogenous IFN-gamma
      declined until 2 days of the infection, then reappeared from 1 week and peaked at
      3 weeks. Endogenous IFN-gamma at 1 and 3 weeks was reduced by in vivo
      administration of anti-CD8 MAb, but not by anti-CD4 MAb or anti-NK 1.1 MAb.
      Granulomatous lesions in the livers and spleens began to appear from 1 week of
      the infection and developed in 3 weeks. In vivo administration of rat anti-IFN
      gamma MAb reduced the development of granulomas. In addition, granuloma formation
      was reduced by depletion of NK cells prior to the infection or depletion of CD8+
      T cells at 1 week of the infection. Based on these findings, it is presumed that
      the biphasic production of IFN-gamma is attributable to NK cells in the early
      phase of the infection and CD8+ T cells in the phase of granuloma formation, and
      that granuloma formation is regulated by NK cells and CD8+ T cells through the
      secretion of endogenous IFN-gamma.

PMID- 8569536
TI  - TCR-independent induction of low responsiveness by chemically fixed cells in
      alloreactive CTL clones and its prevention through cognate cell-cell interaction.
AB  - We established BALB/c-derived CD8+ CTL clones D2-22 (V beta 6+), D2-23 (V beta
      8+) and D2-24 (V beta 8+) specific for B10.D2 minor H antigen. D2-22 and D2-23
      proliferated without producing IL-2 in response to X-ray-irradiated antigenic
      cells, Con A, aCD3, PMA and IL-2. Paraformaldehyde-fixed antigenic spleen cells
      neither induced proliferation in the presence of costimulatory cells nor
      inhibited responses to irradiated antigenic cells added simultaneously. Unlike
      the previously reported results with IL-2-producing CTL clones and Th1 clones,
      the fixed antigenic cells failed to induce antigen-specific unresponsiveness in
      these IL-2-non-producing CTL clones. Instead, the responsiveness of these clones
      to fresh stimulation was found to be reduced severely after 2 days in the culture
      added with either antigenic or syngeneic fixed cells. Induction of their antigen
      nonspecific low responsiveness by the fixed cells was prevented by adding
      irradiated syngeneic cells into the culture or even by increasing the
      concentration of responder D2-23 cells. Close contact of D2-23 and irradiated
      syngeneic cells was required to prevent the reduction of the responsiveness,
      although this cognate cell-cell interaction could be replaced by exogenously
      added IL-2 or PMA. Cytolytic and tumor cell growth inhibitory activities of D2-23
      were also reduced by incubation with the fixed cells, which was prevented by the
      addition of irradiated syngeneic cells. These findings showed the unique
      properties of IL-2-nonproducing CTL clones in signal requirements for maintaining
      normal responsiveness for proliferation and cytolytic activity.

PMID- 8569537
TI  - Analysis of the NH2-terminal 87th amino acid of Escherichia coli GyrA in
      quinolone-resistance.
AB  - The functional contributions of amino acid residue Asp87 of Escherichia coli
      gyrase A protein (GyrA) was analyzed by site-directed mutagenesis. We generated a
      series of mutants, in which Asp87 of GyrA was changed to Ala, Val, Phe, Asn, Ser,
      and Lys. By genetic analysis of gyrA genes in a gyrA temperature-sensitive (Ts)
      background, it was shown that all these mutations caused the quinolone
      resistance. These results indicate that the 87th amino acid of E. coli GyrA must
      have negative charge in expressing the phenotype of quinolone sensitivity. These
      findings also suggest that the carboxyl group of Asp87 may interact with
      quinolone drugs.

PMID- 8569538
TI  - Effect of Porphyromonas gingivalis ATCC 33277 vesicle on adherence of
      Streptococcus mutans OMZ 70 to the experimental pellicle.
AB  - The vesicles of Porphyromonas gingivalis ATCC 33277 strongly aggregated
      Streptococcus cricetus, S. rattus, and S. mutans, but poorly aggregated S.
      sobrinus. The adherence of S. mutans OMZ 70 to hydroxyapatite (HA) coated with
      whole saliva was increased in parallel with the quantity of the vesicles. The
      significant increase of adherence of S. mutans OMZ 70 by the vesicles was also
      observed on the HA coated with parotid saliva, submandibular saliva, serum, and
      type I collagen. These findings suggest that the vesicles may act as a bridge
      between mutans streptococcus and the tooth surface.

PMID- 8569539
TI  - Nucleotide sequence of the gene encoding beta-isopropylmalate dehydrogenase
      (leuB) from Bacteroides fragilis.
AB  - The complete nucleotide sequence of the gene (leuB) coding for beta
      isopropylmalate dehydrogenase of Bacteroides fragilis was determined. An open
      reading frame of 1,061 nucleotides was detected that could encode a polypeptide
      of 353 amino acid residues with a calculated molecular mass of 39,179 Da. The
      deduced amino acid sequence of the beta-isopropylmalate dehydrogenase from B.
      fragilis showed substantial sequence similarity with the beta-isopropylmalate
      dehydrogenases from other bacteria.

PMID- 8569540
TI  - Beef allergy and the Persian Gulf syndrome.
AB  - It is suggested that the Persian Gulf Syndrome (PGS) is caused by beef allergy.
      In the first symptomless phase, as a result of an energetic US Army immunizing
      program, using sera with adjuvants to produce detectable antibody levels, the
      subjects not only developed immunity to the targeted substances, but also became
      sensitized to one or more of the other substances in the immunizing sera, and
      specifically to beef protein. The subjects remained healthy while in the war zone
      on a restricted diet essentially free from beef, but developed PGS after they
      came home, and were again able to obtain steaks and hamburgers.

PMID- 8569541
TI  - A peptide hormone causing abnormal hair-growth associated with malignancy.
AB  - The purpose of this article is to show that abnormal hair-growth associated with
      malignancy (acquired hypertrichosis) is probably caused by a peptide hormone
      which remains to be detected by examining serum, skin, and tumour specimens of
      affected patients. The condition was first described in 1865, and the whole
      literature between 1879 and 1994 is reviewed in Index Medicus and Medline. The
      hypothesis that a peptide hormone is the cause is supported by the condition's
      rapid onset, remission with tumour removal, electronmicroscopical appearance of
      specimens, and results in the experimental model macaque.

PMID- 8569542
TI  - From pseudocholinesterase to human immunodeficiency virus.
AB  - Pseudocholinesterase is a protein for which no function exists in mammals
      including human beings. To date, no substrate has been identified for this
      'enzyme'. Involvement of this protein in the aetiopathogenesis of many diseases,
      such as hyperlipoproteinaemia, is still actively debated. Here, we propose a
      theoretical method to immobilize pseudocholinesterase in hepatocytes using
      antibody bound to liposomes. Conceptually, this approach will have widespread
      application, especially in blocking human immunodeficiency virus replication in
      vivo.

PMID- 8569543
TI  - Aetiopathogenesis of Takayasu's arteritis and BCG vaccination: the missing link?
AB  - Takayasu's arteritis is an inflammatory disease of unknown aetiology involving
      the aorta, its major branches and pulmonary arteries. Historical, epidemiological
      and immunological data are presented which suggest that BCG vaccination in the
      susceptible host might be important in the pathogenesis of Takayasu's arteritis.
      This hypothesis best explains the various known facts about the disease.

PMID- 8569544
TI  - The role of the immune system in severe ovarian hyperstimulation syndrome.
AB  - The ovarian hyperstimulation syndrome is a serious, and potentially life
      threatening, complication of ovulation induction. Hitherto, there has been no
      reliable test which will predict patients who will subsequently develop ovarian
      hyperstimulation syndrome. Recently, evidences have accumulated concerning the
      interaction between the immune and reproductive systems which results from
      sharing certain lymphohaematopoietic cytokines and their receptors. Furthermore,
      several cytokines have been implicated in the prediction and pathophysiology of
      ovarian hyperstimulation syndrome. If this is true, it may be possible to modify
      the patients' immunological homeostasis by passive immunization with intravenous
      immunoglobulin (IVIg) and thus to prevent ovarian hyperstimulation syndrome.

PMID- 8569545
TI  - Implications of the sequence similarities between tau and myelin basic protein.
AB  - The minor myelin basic protein (MBP) isoforms with M(r) 21.5 and 17 kDa and the
      cytoskeletal proteins actin and tubulin are enriched in an interlamellar
      junctional specialization within central nervous system (CNS) myelin, the radial
      component (RC). To pursue the notion that there are specific interactions between
      these constituents, we searched for sequences in MBP that are homologous to
      sequences in the tubulin-binding protein tau. We found that the sequence motifs
      that are homologous to the phosphorylation and tubulin binding sites of tau (-RSP
      and -KPGFG-) are also within the exon 2 and 6-encoded peptides of MBP. The 
      KPGFG- motif is unique to MBP when compared to other myelin proteins, and is
      highly conserved in the MBPs among vertebrate species. The physicochemical
      properties of the MBP and tau peptides that contain these sequences and their
      predicted secondary structures suggest that the peptides containing these motifs
      are hydrophilic and folded largely in turn and coil. This implies that the motifs
      are located at the protein surface where they would be accessible for
      interactions with other components of proteins or lipids. We propose that these
      putative phosphorylation and tubulin-binding sites in MBP may play functional
      roles in CNS myelin that are analogous to their roles in tau.

PMID- 8569546
TI  - Anabolic effects of insulin on bone suggest a role for chromium picolinate in
      preservation of bone density.
AB  - Activation of osteoclasts by parathyroid hormone (PTH) is mediated by PTH
      stimulation of osteoblasts, and is dependent on a PTH-induced rise in protein
      kinase C activity. Physiological levels of insulin reduce the ability of PTH to
      activate protein kinase C in osteoblasts, suggesting that insulin may be a
      physiological antagonist of bone resorption. In addition, insulin is known to
      promote collagen production by osteoblasts. These findings imply that efficient
      insulin activity may exert an anabolic effect on bone, and rationalize the many
      clinical studies demonstrating reduced bone density in Type I diabetes. Recently,
      the insulin-sensitizing nutrient chromium picolinate has been found to reduce
      urinary excretion of hydroxyproline and calcium in postmenopausal women,
      presumably indicative of a reduced rate of bone resorption. This nutrient also
      raised serum levels of dehydroepiandrosterone-sulfate, which may play a
      physiological role in the preservation of postmenopausal bone density. The impact
      of chromium picolinate (alone or in conjunction with calcium and other
      micronutrients) on bone metabolism and bone density, merits further evaluation in
      controlled studies.

PMID- 8569547
TI  - Inhibition of citrate lyase may aid aerobic endurance.
AB  - Owing to a substantial increase in glucose uptake by working muscle, glucose
      homeostasis during sustained aerobic exercise requires a severalfold increase in
      hepatic glucose output. As exercise continues and liver glycogen declines, an
      increasing proportion of this elevated glucose output must be provided by
      gluconeogenesis. Increased gluconeogenic efficiency in trained individuals is a
      key adaptation promoting increased endurance, since failure of hepatic glucose
      output to keep pace with muscle uptake rapidly leads to hypoglycaemia and
      exhaustion. Pre-administration of (-)-hydroxycitrate, a potent inhibitor of
      citrate lyase found in fruits of the genus Garcinia, may aid endurance during
      post-absorptive aerobic exercise by promoting gluconeogenesis. Carnitine and
      bioactive chromium may potentiate this benefit. The utility of this technique may
      be greatest in exercise regimens designed to promote weight loss.

PMID- 8569549
TI  - Hypothesis on cellular ATP depletion and adenosine release as causes of heart
      failure and vasodilatation in cardiovascular beriberi.
AB  - Cardiovascular beriberi is a syndrome caused by thiamine deficiency and
      characterized by systemic vasodilatation, heart failure and lactic acidosis. The
      occurrence of heart failure and vasodilatation is yet unexplained: neither
      theoretical nor experimental data are known. In this article, it is suggested
      that a fall of cellular ATP levels causes heart failure and that the release of
      adenosine is the cause of vasodilatation.

PMID- 8569548
TI  - A molecular model for bipolar affective disorder.
AB  - The biological basis of bipolar disorder is not known. Models for the illness
      have been proposed that were based on the neurobiological effects of
      pharmacological agents that affect mood. Although of great interest, these models
      have not adequately explained the striking clinical pattern of illness in which
      patients may experience either unipolar episodes or bipolar cycles of mania and
      depression. We now present a new model suggesting that the unique clinical
      heterogeneity found in patients with bipolar disorder could be explained by a
      defect in a 'downstream' portion of a signal transduction pathway that can
      regulate two or more neurotransmitter systems that have opposite effects on
      neuronal activity. This model may target specific candidate genes for involvement
      in bipolar disorder.

PMID- 8569550
TI  - On the nature of the link between malignant hyperthermia and exertional
      heatstroke.
AB  - Malignant hyperthermia (MH) is a rare myopathy inducing severe accident when
      carriers are exposed to triggering agents. MH susceptibility (MHS) is assessed by
      pharmacological tests performed on muscle strips. Exertional heat stroke (EHS) is
      a severe accident occurring during long and strenuous exercise. It has been
      observed that numerous EHS patients are susceptible to MH according to
      pharmacological tests. Because most of those EHS-MHS subjects were soldiers, we
      hypothesize that military duty could select subjects with infraclinical myopathy
      and therefore would increase the MHS:EHS subject ratio.

PMID- 8569551
TI  - Acupuncture--from empiricism to science: functional background to acupuncture
      effects in pain and disease.
AB  - Acupuncture is part of Traditional Chinese Medicine, a system with an empirical
      basis which has been used in the treatment and prevention of disease for
      centuries. A lack of scientific studies to prove or disprove its claimed effects
      led to rejection by many of the western scientific community. Now that the
      mechanisms can be partly explained in terms of endogenous pain inhibitory
      systems, the integration of acupuncture with conventional medicine may be
      possible. Its use for pain relief has been supported by clinical trials and this
      has facilitated its acceptance in pain clinics in most countries. Acupuncture
      effects must devolve from physiological and/or psychological mechanisms with
      biological foundations, and needle stimulation could represent the artificial
      activation of systems obtained by natural biological effects in functional
      situations. Acupuncture and some other forms of sensory stimulation elicit
      similar effects in man and other mammals, suggesting that they bring about
      fundamental physiological changes. Acupuncture excites receptors or nerve fibres
      in the stimulated tissue which are also physiologically activated by strong
      muscle contractions and the effects on certain organ functions are similar to
      those obtained by protracted exercise. Both exercise and acupuncture produce
      rhythmic discharges in nerve fibres, and cause the release of endogenous opioids
      and oxytocin essential to the induction of functional changes in different organ
      systems. Beta-endorphin levels, important in pain control as well as in the
      regulation of blood pressure and body temperature, have been observed to rise in
      the brain tissue of animals after both acupuncture and strong exercise.
      Experimental and clinical evidence suggest that acupuncture may affect the
      sympathetic system via mechanisms at the hypothalamic and brainstem levels, and
      that the hypothalamic beta-endorphinergic system has inhibitory effects on the
      vasomotorcenter, VMC. Post-stimulatory sympathetic inhibition which proceeds to a
      maximum after a few hours and can be sustained for more than 12 hours, has been
      demonstrated in both man and animals. Experimental and clinical studies suggest
      that afferent input in somatic nerve fibres has a significant effect on autonomic
      functions. Hypothetically, the physiological counterpart lies in physical
      exercise, and the effect can be artificially reproduced via various types of
      electrical or manual stimulation of certain nerve fibres.

PMID- 8569552
TI  - The immunorejection of neoplasia in a theoretical model.
AB  - A theoretical model is presented based on the idea that the immune system of a
      patient with a tumour can cross-react against transplanted normal foreign cells
      as well as against the patient's own neoplastic cells, thereby rejecting both.
      This hypothesis is shown in a diagram, the potential use of which is discussed.

PMID- 8569553
TI  - Essential hypertension: could the basic defect be in blood supply of vasomotor
      centre?
AB  - Various factors have been implicated in the pathogenesis of essential
      hypertension, although the exact cause of essential hypertension is still
      unknown. In this paper it is suggested that the basic pathology in essential
      hypertension may be an inherited defect in the blood supply of that part of
      reticular formation of rostral ventrolateral medulla which contains the pressor
      area. The posited defect is one in which the arterial branch supplying blood to
      the above-mentioned pressor area of vasomotor center arises from an artery which
      is stenosed. The other branches of this stenosed artery supply adjacent areas of
      medullary reticular formation concerned with other neurological functions. Due to
      this stenosis there is ischaemia of the pressor area resulting in increased
      systemic arterial pressure. During stress, the blood requirement of adjacent
      areas of the reticular formation (whose function is still not clearly defined)
      may increase, thus further decreasing blood flow to vasopressor area and
      increasing the cerebral ischaemic response. After a prolonged time, this
      increased blood pressure can cause hyaline arteriolar nephrosclerosis in kidney,
      which may participate in the maintenance of elevated systemic arterial pressure.

PMID- 8569554
TI  - Molecular mechanism of biological responses to homoeopathic medicines.
AB  - Assuming that homeopathy is effective beyond the placebo effects, its biological
      explanation in favour of the hypothesis of the hydrate-structure formation is
      presented. Since cell-surface proteins are likely to be activated by the
      hydration-shell structure of molecules in some cases, the interaction between
      cell-surface proteins and the putative clathrate-like hydrate microcrystals
      formed during the homoeopathic dilution process is suggested as a primary
      molecular mechanism of biological responses to homoeopathic medicines. This paper
      examines the probable protein-microcrystal interaction, forcusing on the cases in
      which silicon dioxide (silica) microcrystals cause inflammation and in which
      hydrate microcrystals may be formed during general anesthesia.

PMID- 8569555
TI  - Folic acid as a cancer-preventing agent.
AB  - Higher intakes of folic acid-rich foods such as vegetables, legumes, and whole
      grains are associated with lower incidence of carcinomas in international
      comparisons and case-control studies. Deficiency of folic acid in experimental
      studies causes DNA damage that resembles the DNA damage seen in cancer cells. The
      requirement for folic acid in DNA synthesis and DNA methylation provides a
      plausible mechanism for a mutagenic effect of a low-folate diet. It is suggested
      that cancer can be initiated by DNA damage that results from folic acid
      deficiency. The relatively low level of folic acid in North American diets might
      be the underlying reason for high rates of many cancers in North America.

PMID- 8569557
TI  - Con A cytotoxicity: a model for the study of key signaling steps leading to
      lymphocyte apoptosis in AIDS?
AB  - Lymphocytes respond to mitogens, viruses and other activation agents with
      hydrogen peroxide or reactive oxygen bursts which may originate at or near the
      cell membrane. It has been shown that a very small increase in the ratio of Con A
      cells results in a rapid switchover from mitogenicity to cytotoxicity. It is
      hypothesized that the change from mitogenicity to cytotoxicity correlates with
      the strength and duration of the hydrogen peroxide or reactive oxygen bursts
      which in turn depends on the number of molecules of the activation agent bound
      per cell. This hypothesis is presented and discussed in the context of the
      apoptosis (programmed cell death) and pro-oxidant-antioxidant hypothesis of CD4+
      T-cell and B-cell subpopulation depletion in AIDS.

PMID- 8569556
TI  - A co-evolutionary theory of sleep.
AB  - Based on recent experimental evidence, a novel theory of sleep function and
      regulation is advanced, stating that sleep primarily evolved to protect the brain
      against a wakefulness-dependent increase in the permeability of the blood-brain
      barrier. A restitutional mechanism for the blood-brain barrier had to co-evolve
      against the omnipresent gut-derived bacterial cell wall constituents, because
      these and their elicited cellular responses increase blood-brain barrier
      permeability and potentially harm nervous tissue. Thus, in order to develop a
      highly organized cerebral structure, an immune-like response specific for the
      brain co-evolved during the phylogeny of the symbiosis between animals and gut
      bacteria to control the detrimental effects of bacterial cell wall constituents.
      In the course of further evolution, the sleep-associated 'controlled inflammatory
      state' of the brain employed the growth-factor activities of locally activated
      cytokines to enforce cerebral development and the maintenance of cognitive
      functions.

PMID- 8569558
TI  - Managing HIV. Part 2: Phases of disease. 2.1 Primary HIV infection.
AB  - The most important principle in managing primary HIV infection is not to miss the
      diagnosis. It presents an early opportunity for counselling and education aimed
      at maximising quality of life and minimising the risk of transmitting HIV
      (particularly high during the viraemia of primary infection).

PMID- 8569559
TI  - Managing HIV. Part 2: Phases of disease. 2.2 Early HIV-induced immune deficiency.
AB  - From the resolution of primary infection until the CD4 cell count falls below
      500/microL, people with HIV are usually functioning at their normal capacity
      physically, mentally and socially. However, HIV is replicating actively within
      lymph nodes during this period of early immune deficiency. It is important to
      determine the rate of immune depletion and to assess what factors, if any, may be
      hastening that progression.

PMID- 8569560
TI  - Managing HIV. Part 2. Phases of disease. 2.3 HIV and intermediate immune
      deficiency.
AB  - Intermediate immune deficiency is defined by a CD4 cell count between 500/microL
      and 200/microL. This phase is one of increasing therapeutic intervention, mostly
      for minor infections of skin and mucous membranes and mostly manageable within
      general practice. Most people with HIV begin antiretroviral therapy during this
      phase. Regular monitoring of CD4 cell count is essential for making appropriate
      therapeutic decisions and for determining prognosis.

PMID- 8569561
TI  - Managing HIV. Part 2: Phases of disease. 2.4 HIV and advanced immune deficiency.
AB  - Advanced immune deficiency is defined as a CD4 cell count below 200/microL. This
      phase is marked by considerable medical intervention requiring close coordination
      between general practitioner and specialist, with the goal of minimising the
      patient's time in hospital. The patient must be assisted with the psychological
      adjustments that lead to death with dignity. Managing HIV in all its
      manifestations will make a great difference to the quality of both life and
      death.

PMID- 8569562
TI  - Australian contributions to the study of infectious disease.
AB  - Despite the ?brain drain? and economic and other pressures, Australians have made
      many internationally significant contributions to the study of infectious
      disease.

PMID- 8569563
TI  - Emerging resistance in Enterococcus spp.
AB  - Enterococcus spp. are becoming increasingly important nosocomial pathogens. They
      are intrinsically resistant to most antibiotics, and effective therapy depends
      primarily on the penicillins, vancomycin and the aminoglycosides. Under
      antibiotic selection pressure they have developed high level resistance to these
      agents, and the first vancomycin-resistant enterococcal infection in Australia
      was described recently. The vancomycin-resistance genes are of particular concern
      because of their potential to transfer to other gram-positive organisms. The
      prevention and control of resistant enterococci is a major challenge that is best
      met by a combination of active infection control measures and restriction of
      broad-spectrum antibiotic use.

PMID- 8569564
TI  - Multidrug-resistant tuberculosis: prevention is better than cure.
AB  - The incidence of tuberculosis, in decline in Western countries for years, is
      increasing again. Inadequate therapy leads to the emergence of multidrug
      resistant tuberculosis, which is difficult to treat and for which there is no
      effective chemoprophylaxis. Prevention is the most important strategy.

PMID- 8569565
TI  - The recently discovered hepatitis G virus.

PMID- 8569566
TI  - Adolescence: a second risk period of hepatitis B transmission in immigrant
      families resident in Australia?

PMID- 8569567
TI  - High-level ciprofloxacin-resistant Neisseria gonorrhoeae and heterosexually
      acquired infections in Victoria.

PMID- 8569568
TI  - Group B streptococcal infection in neonates.

PMID- 8569569
TI  - Hepatitis C virus transmission to heterosexual partner: bedroom or bathroom
      hazard?

PMID- 8569570
TI  - Cataloguing and containing infection in Australia.

PMID- 8569571
TI  - Vaccine-preventable childhood diseases in Australia.

PMID- 8569572
TI  - What we should be doing about tuberculosis in Australia.

PMID- 8569573
TI  - Drug-resistant Streptococcus pneumoniae: the beginning of the end for many
      antibiotics? Australian Group on Antimicrobial Resistance (AGAR)
AB  - OBJECTIVE: To determine the levels of antibiotic resistance in Streptococcus
      pneumoniae in Australia. DESIGN: Prospective, Australia-wide, laboratory-based
      survey. SETTING: 27 hospital and private laboratories around Australia, from
      January 1994 to August 1995. SUBJECTS: First 100 patients with clinically
      significant isolates of S. pneumoniae at each laboratory. OUTCOME MEASURES:
      Resistance to penicillin (determined from penicillin minimum inhibitory
      concentration [MIC] measured by the Etest), erythromycin, trimethoprim
      sulfamethoxazole, tetracycline, chloramphenicol, cefotaxime and ceftriaxone.
      RESULTS: A total of 2396 isolates were tested (including 537 invasive isolates
      and 740 from children). Penicillin resistance was seen in 161 isolates (6.7%),
      including 17 with high level resistance. Penicillin resistance rates were
      significantly lower in invasive than in non-invasive strains (3.7% versus 7.6%;
      odds ratio [OR], 0.47; 95% confidence interval [CI], 0.28-0.77; P = 0.001). There
      was no significant difference in penicillin resistance rates between children (<
      15 years) and adults (7.3% versus 6.5%; OR, 1.14; 95% CI, 0.80-1.63; P = 0.47).
      Resistance rates were higher for most other antibiotics than for penicillin
      (chloramphenicol, 6%; erythromycin, 11%; tetracycline, 15%; and trimethoprim
      sulfamethoxazole, 42%). No high level resistance was seen to third generation
      cephalosporins, but 17 of 109 penicillin-resistant isolates tested (16%)
      displayed intermediate resistance to cefotaxime. Rates of antibiotic resistance
      varied between States, with the lowest rates in Tasmania. CONCLUSIONS: Antibiotic
      resistance levels in S. pneumoniae are increasing in Australia and high level
      penicillin resistance is being encountered for the first time (including in
      invasive strains). This will lead to an increasing number of therapeutic dilemmas
      and possible therapeutic failures, especially important in meningitis.

PMID- 8569574
TI  - Evolution of resistance in Staphylococcus aureus in Australian teaching
      hospitals. Australian Group on Antimicrobial Resistance (AGAR).
AB  - OBJECTIVE: To assess the changes in antibiotic resistances in Staphylococcus
      aureus, both methicillin-susceptible and methicillin-resistant strains, in
      Australia. DESIGN: Retrospective review of data collected annually. SETTING:
      Twenty metropolitan teaching hospitals in the six States of Australia and the
      Australian Capital Territory from 1988 to 1994. OUTCOME MEASURES: Changes in
      prevalence and resistance rates of methicillin-resistant S. aureus (MRSA) and
      methicillin-susceptible strains, based on antibiotic susceptibility testing of
      clinical isolates of S. aureus. RESULTS: Prevalence of MRSA has remained constant
      on the eastern seaboard of Australia. A distinctive strain of MRSA emerged in
      Western Australia which had different antimicrobial susceptibilities. Resistances
      emerged in MRSA strains from eastern Australia, principally to ciprofloxacin and
      rifampicin, while resistance to fusidic acid remained stable and resistance to
      chloramphenicol significantly declined. Resistances in methicillin-susceptible
      strains remained fairly stable, except for a decline in resistance levels for
      tetracycline. High levels of resistance were seen to penicillin, moderate levels
      to erythromycin and low levels to trimethoprim and fusidic acid in methicillin
      susceptible strains. CONCLUSIONS: The continued high prevalence of and increasing
      resistance in MRSA in some Australian hospitals have meant that some strains are
      now untreatable with oral antibiotics.

PMID- 8569575
TI  - Non-toxigenic Corynebacterium diphtheriae biovar gravis: evidence for an invasive
      clone in a south-eastern Australian community.
AB  - OBJECTIVE: To determine the prevalence and clonality of non-toxigenic
      Corynebacterium diphtheriae biovar gravis in a community with two cases of
      endocarditis caused by this organism. SETTING: A Koorie (Aboriginal) community in
      Gippsland, eastern Victoria, in 1994. METHODS: Nose and throat swabs were
      collected from 359 community contacts of the cases and cultured for C.
      diphtheriae. Strains isolated from the contacts were compared by pulsed-field gel
      electrophoresis (after digestion with Sma1, Not1 and Sfi1) with those from the
      invasive cases in the same community, another invasive case in Victoria, a
      cluster of invasive cases in New South Wales (NSW) (1990-1991), and other stored
      strains isolated from skin ulcers and sore throats. RESULTS: Non-toxigenic
      strains of C. diphtheriae biovar gravis were isolated from throat swabs of five
      of the case contacts. Uniform DNA patterns were found for the two community
      cases, the other Victorian case, nine of ten isolates from NSW, and the five
      throat isolates from case contacts. CONCLUSION: An invasive clone of C.
      diphtheriae biovar gravis appears to have been responsible for the three
      Victorian cases of endocarditis. It was also present among case contacts and
      responsible for previous invasive cases in NSW. Prophylactic treatment should be
      considered for clearly defined contacts in all instances where C. diphtheriae is
      isolated from a normally sterile site, regardless of the toxigenic nature of the
      strain.

PMID- 8569577
TI  - Viral haemorrhagic fevers: current status, future threats.
AB  - In developing countries, the major outbreaks of viral haemorrhagic fevers such as
      Marburg, Ebola and Lassa fever viruses have been nosocomially spread. The high
      mortality and absence of specific treatment have had a devastating effect.
      Epidemics of this highly contagious disease remain a constant threat to Australia
      and, as a result, carefully planned laboratory and public health strategies and
      clinical infection control measures have been instituted for the management of
      suspected cases.

PMID- 8569576
TI  - The emergence of Mycobacterium ulcerans infection near Melbourne.
AB  - OBJECTIVE: To document the emergence of new foci of Mycobacterium ulcerans
      infection (Bairnsdale ulcer) in Victoria. METHODS: From data kept by one of us
      (JAH) and records from the Mycobacterium Reference Laboratory, Fairfield
      Hospital, we reviewed cases of M. ulcerans infection in Victoria between 1980 and
      1995, and identified those apparently acquired outside the east Gippsland endemic
      region. A case was defined as a person with a lesion suggestive of M. ulcerans
      infection, from which the organism had been cultured or, in the absence of
      culture information, from which a histological specimen characteristic of M.
      ulcerans infection had been obtained. RESULTS: We identified 45 people who
      appeared to have acquired their infections in Victoria but outside the east
      Gippsland region. A new focus appeared on the northern shores of Western Port,
      near Melbourne, in 1982, and there was a dramatic increase in cases between 1991
      and 1994 associated with foci on Phillip Island, and in the Frankston-Langwarrin
      area of outer suburban Melbourne. Single cases came from Crib Point, Narre Warren
      and Bendigo. CONCLUSIONS: There have been at least three new foci of M. ulcerans
      infection within 80 km of Melbourne since 1982. Victorian clinicians should
      consider the possibility of Bairnsdale ulcer when dealing with unusual skin
      lesions.

PMID- 8569578
TI  - HTLV-I in Australia and Oceania: long-term resident or recent immigrant?
AB  - Human T-cell lymphotropic virus type I (HTLV-I) has a worldwide distribution;
      infection rates of up to 14% have been found in Aboriginal communities, but there
      is little evidence of typical HTLV-I-associated disease. The strains among
      Australian Aboriginals and Melanesians are more closely related to each other at
      the molecular level than to strains from Africa, Japan and the Caribbean basin.
      The clinical significance of these Oceanic strains of HTLV-I in endemically
      infected communities is unclear.

PMID- 8569579
TI  - New hepatitis viruses: are there enough letters in the alphabet?
AB  - Testing is now available for five recognised hepatitis viruses (A, B, C, D and
      E), and molecular technology is uncovering further hepatotropic viruses. An
      enteric agent isolated from human stool samples and transmitted experimentally to
      primates is a candidate hepatitis F virus. A provisionally designated blood-borne
      hepatitis G virus is associated with acute and chronic non-ABCDE hepatitis and
      has a worldwide distribution. A group of flavi-like viruses, the GB group, also
      blood borne, has also been reported. The role of two of these viruses, GBV-A and
      GBV-B, in human viral hepatitis has not been determined, but a third agent, GBV
      C, is associated with acute and chronic hepatitis and appears to be a West
      African variant of hepatitis G. Our current knowledge suggests that the hepatitis
      alphabet may need to be extended even after inclusion of some of these new
      viruses.

PMID- 8569580
TI  - Mosquito-borne viruses and epidemic polyarthritis.
AB  - The two most common mosquito-borne viruses associated with epidemic polyarthritis
      and polyarticular disease are Ross River and Barmah Forest viruses, accounting
      for about 90% and 10%, respectively, of serologically confirmed cases. Occasional
      cases of polyarticular disease in Australia have been associated with infection
      by other mosquito-borne arboviruses, but the role of these viruses in human
      disease remains to be confirmed.

PMID- 8569581
TI  - Smallpox at Kurri Kurri. 1915.

PMID- 8569582
TI  - "Natural" therapy for infectious diseases.
AB  - Introduce the right kind of bacteria and several pathogens lose their niche in
      the human host--that's the rationale behind probiotic therapy. These and some
      other "natural" therapies are popular with patients and increasingly supported by
      research results.

PMID- 8569583
TI  - Managing HIV. Part 1: Principles. 1.1 HIV medicine in the mainstream.
AB  - After more than a decade of special treatment, HIV medicine is ready to enter the
      mainstream of medical practice in developed countries. Access to a conveniently
      located, well informed, primary care doctor who works well with an appropriate
      specialist is the cornerstone of best medical care for chronic illness, including
      HIV disease. Managing HIV is part of the second phase of a national educational
      program aimed at equipping more doctors with the skills to care for people with
      HIV.

PMID- 8569584
TI  - Managing HIV. Part 1: Principles. 1.2 Strategies of care in managing HIV.
AB  - Apply the science, use a team approach, help patients to promote their own
      health, ensure access to support and accept a public health role. These are the
      practical lessons of our experience in HIV medicine.

PMID- 8569585
TI  - [Depressing data on depression].

PMID- 8569586
TI  - [Calcium antagonists--much noise about nothing?].

PMID- 8569587
TI  - [Decreased saliva secretion. A pharmacologic effect with sequelae for oral
      health].

PMID- 8569588
TI  - [Treatment of ulcus cruris. What is the role of wound dressings?].

PMID- 8569589
TI  - [Prevention of thyroid diseases with iodine].

PMID- 8569590
TI  - Implementation of a personal computer (PC) as a graphic station into the system
      MicroDELTA-MaxDELTA for processing of nuclear medicine images.
AB  - One of the possibilities to integrate PC into the system "MicroDELTA-MaxDELTA"
      for acquisition and nuclear medicine image processing is introduced. A 386 IBM
      compatible personal computer is connected into the local area network with
      MicroVAX II, which is the part of a "MicroDELTA-MaxDELTA" system. "NuMed"
      application, which enables simple and efficient manipulation of patient studies
      and also their archiving, processing and generating reports, is developed in
      WINDOWS environment. Considering the fact that existing system fully satisfies
      the acquisition requirements, the whole conception has the aim to upgrade the
      digital image processing, and initiate further development of the whole system.

PMID- 8569591
TI  - TESLA Accelerator Installation at Vinca. Production of radioisotopes for nuclear
      medical applications.
AB  - The construction of the TESLA Accelerator Installation has been in progress under
      way at Vinca. It was designed so that the parameters of its main part-the VINCY
      Cyclotron enable, besides other applications, also the production of a number of
      radioisotopes which can be used in nuclear medicine. The production of a given
      radioisotope includes the choice of nuclear reaction (type, energy and beam
      current of accelerated particles, cross section, yield, etc), target (chemical
      form, isotopic composition, thermal stability), procedure of chemical treatment
      of the target after irradiation, procedure of labeling and quality control of the
      obtained radiopharmaceutical. In the paper these aspects are shown on the example
      of the production of radioisotope 123I.

PMID- 8569592
TI  - Evaluation of left ventricular diastolic function by radionuclide
      ventriculography in patients with coronary artery disease.
AB  - Radionuclide ventriculography (RNV) was used to assess the peak filling rate
      (PFR) in 20 patients with coronary artery disease (CAD). Dipyridamole RNV was
      used in 5 normal subjects and 10 patients with CAD with the view to evaluating
      PFR increase. Significant difference in PFR values was established between normal
      subjects and CAD patients. Decreased value of PFR was found in 78% CAD patients,
      and 72% of them had normal ejection fraction (EF). During dipyridamole RNV
      increase of PFR was not significantly different between normals and CAD patients.
      The peak filling rate is a very sensitive indicator of LV dysfunction in CAD
      patients, and is useful in early detection of abnormalities in diastolic function
      in CAD patients.

PMID- 8569593
TI  - Myocardial perfusion imaging using 99mTc-MIBI in patients with dilated
      cardiomyopathy--methodology and its clinical use.
AB  - The aim of the study was to demonstrate the methodology of investigation of
      myocardial perfusion and viability using 99mTc-MIBI in patients with dilated
      cardiomyopathy and to estimate its clinical use. Myocardial perfusion and
      viability were investigated by using the planar and SPECT scintigraphy and by
      estimating the wall motion of the myocardium. The foci of decreased myocardial
      viability were found in 7 patients. One patient had perfusion defect only at
      stress. Analyzing the patients data, by using the gated studies, we found various
      degrees of wall motion myocardial abnormalities.

PMID- 8569594
TI  - 201Tl reinjection and late redistribution in the detection of viable myocardium.
AB  - Nonreversible (NRD) myocardial perfusion defects following stress-rest (S/R)
      201Tl studies may often be found in ischemic areas. 201Tl reinjection immediately
      following S/R scintigraphy and 24h (late) redistribution has been shown to
      identify late reversible defects (LRD) indicative of viable myocardium. Twenty
      two patients with CAD were studied. All subjects underwent S/R 201Tl (37MBq) 24h
      later (1 group). Six out of 22 patients had late scintigraphy without new doses
      of 201Tl. Ischemia was considered present when the poststress count density was
      less for more than 25% than the resting count density. Out of 29 NRDs. 15
      segments exhibited late reversibility following 201Tl reinjection reflecting
      viability (II group). One out of 8 NRDs demonstrated late reversibility following
      late redistribution imaging (II group). Thus, 201Tl reinjection following S/R
      imaging appeared to be more effective in maximizing the detection of viable
      myocardium than late redistribution. It is equally useful in patients with NRD
      following S/R scintigraphy and no history of prior myocardial infarction (MI) or
      those who had MI.

PMID- 8569595
TI  - Measuring of cardiolipin antibodies and plasma lipids in different stages of
      coronary disease.
AB  - The study shows that antibodies to cardiolipin which are commonly found in young
      postinfarction cases may present a high risk for recurrent coronary
      manifestations. IgG and IgM antibodies to cardiolipin (C1Ab) were determined in
      50 healthy individuals and 72 patients with coronary disease: 26 with acute
      infarction (A) and 24 with chronic infarction (C) as well as 22 with angina
      pectoris (AP). Lipid status parameters as risk factors were measured in all
      patients: total cholesterol, LDL, HDL cholesterol, triglycerides and
      apolipoprotein (a). Out of 72 patients suffering from coronary disease 20 (27.7%)
      had elevated C1Ab IgG (12.36 +/- 3.7 GPLU/ml). Rise of C1Ab IgM was not evidenced
      in any of the patients. C1Ab IgG were significantly elevated (p < 0.01) in
      patients with chronic myocardial infarction and angina pectoris (p < 0.05) while
      in cases of acute myocardial infarction significant elevation of these antibodies
      was not evidenced.

PMID- 8569596
TI  - The role of biphasic scintigraphy with 99mTc-HMPAO leukocytes in detection of
      synthetic vascular graft infections--preliminary results.
AB  - The study presents preliminary results and suggests the role of scintigraphy of
      synthetic vascular prosthesis by 99mTc-HMPAO labelled leukocytes for detection of
      graft infections. Analysis of the results obtained revealed true positive in 6,
      true negative in 3 and suspicious findings in 3 patients (in one of them the
      suspicious was confirmed on reoperation). False positive and false negative
      results were not obtained. Early and accurate diagnosis of occult infection of
      the synthetic vascular graft is of utmost importance for the prompt starting of
      the therapy. Due to its high sensitivity and specificity, 99mTc-HMPAO-leukocytes
      scintigraphy is a very useful method for the detection of graft infections.

PMID- 8569597
TI  - Targeting of non-small cell lung cancer using HMFG1-99mTc monoclonal antibodies.
AB  - Anti HMFG1 monoclonal antibodies labeled with 99mTc were used for the detection
      of non-small cell lung cancers and their metastases in 18 patients (12 squamous
      cell cancers, 2 large cell lung cancers, 1 adenocarcinoma and 3 undifferentiated
      non-small cell lung cancer). According to performed therapy all patients were
      divided into three groups: group 1 consisted of 13 patients who had not received
      chemotherapy or radiotherapy before immunoscintigraphy (IS), group 2 included 3
      patients who had undergone IS during external beam radiotherapy, and group 3 (two
      patients) who had received both chemotherapy and radiotherapy before IS. After
      antibody administration planar scintigraphy of the head and neck, chest in
      anterior and posterior projection, anterior abdomen, pelvis, thighs and calves
      was obtained at 10 minutes, 5 hours and 24 hours. The scans were interpreted semi
      quantitatively using T/NT ratio. In the first group IS was found true positive in
      5/13 patients (38%), and T/NT ratio ranged from 1.3-1.5. In the second group all
      three patients were true positive and T/NT ratio ranged from 1.76 to 2.1. In the
      third group both patients were found false negative. Successful metastases
      detection was found in 4/13 patients (30%).

PMID- 8569598
TI  - Application of 99mTc-DTPA aerosol in evaluation of pulmonary epithelial
      permeability.
AB  - Measuring of the rate of radioactivity decrease of inhaled 99mTc-DTPA aerosol may
      detect disorders of alveocapillary membrane integrity. The study included 21
      patients (11 non-smokers and 10 smokers) suffering from different pulmonary
      diseases (pulmonary embolism - PE; chronic obstructive pulmonary disease - COPD;
      pneumonia - PN; occupational diseases - OD) in order to detect disorders of
      pulmonary epithelial permeability (PEP) and 2 healthy individuals (non-smokers)
      with normal findings (NF). DTPA was labelled using the standard procedure with
      1480 MBq 99mTc in 1 ml of physiologic saline. Patients with nasal obstruction
      inhaled aerosol for 2.5 min. particle size 0.8 micron produced in a nebulizer
      connected to O2. After that gamma scintillation camera and computer were used for
      data acquiring in dynamic mode. After that ventilation and perfusion scintigraphy
      of the lungs was performed in four standard projections. Data processing was
      conducted with ROI drawing after both lungs on the added image. Clearance value
      was expressed in T1/2 (min), while the curves had monoexponential shape in all
      patients. In the non-smoking group mean clearance value for both lungs in
      patients suffering from PE, COPD and PN did not differ from NF. Clearance in the
      part of the lungs affected with disease (pneumonia, embolism) was faster than in
      healthy pulmonary tissue. In sick smokers, however, mean pulmonary clearance
      value was higher than in non-smokers, irrespective of the type of disease.
      Pulmonary clearance in individuals suffering from occupational diseases was also
      accelerated, irrespective of the fact whether the patients smoked or not.

PMID- 8569599
TI  - Short-term effects of captopril (Katopil) on renal haemodynamics and function in
      hypertensive patients.
AB  - Short-term effects of captopril on the renal-hemodynamics and function were
      evaluated in 75 adult hypertensive patients. The behaviour of total and divided
      effective renal plasma flows (ERPF) and parenchymal mean transit time (PaMTT)
      implied three types of effect the premedication exerted on local renal
      haemodynamics and function: a protective one, no significant changes and an
      adverse one. In the vast majority of the cases captopril induced reduction in
      systemic blood pressure, was observed, irrespective of the renal response. The
      methodology presented seems to be a sensitive test for the selection of patients
      in whom an overall beneficial effect from the therapy with captopril monotherapy
      is expected.

PMID- 8569600
TI  - Effects of nonsteroidal antiinflammatory drugs on renal plasma flow and
      glomerular filtration rate in patients with glomerulonephritis.
AB  - We investigated the effects of NSAIDs (Ibuprofen) on renal plasma flow (RPF) and
      glomerular filtration rate (GFR) in patients with glomerulonephritis. The study
      included 98 patients (53 men and 45 women) with idiopathic glomerulonephritis.
      All of the patients received Ibuprofen 1200 mg (3x400) during 7 days. Before and
      after the treatment with Ibuprofen ERPF (clearance of 131I-Hippuran) and GFR
      (clearance of 99mTc-DTPA) were determined. In our patients administration of
      Ibuprofen was associated with a significant reduction in renal plasma flow and
      glomerular filtration rate. In patients with reduced renal function the decrease
      in RPF and GFR after Ibuprofen was significantly greater than in patients with
      normal renal function.

PMID- 8569601
TI  - Renal osteodystrophy--pathophysiological aspects.
AB  - The aim of this study was to evaluate status of bone metabolism in patients on
      chronic maintenance dialysis, to elucidate dominant mechanisms in the genesis of
      renal osteodistrophy (ROD) with simultaneous measuring of biochemical regulators
      and parameters of bone metabolism and scintigraphic study of metabolic activity
      of the skeleton. We found that disturbance of skeletal homeostasis existed in all
      patients, dominant hyperparathyroid bone disease was found in most of them, mixed
      uremic osteodistrophy (hyperparathyroidism and vitamin D deficiency) was observed
      in less percent, i.e. only in 6% renal bone disease with low turnover due to
      osteomalacia or adynamic bone disease was present. Simultaneous determinations of
      most relevant factors of bone metabolism and scintiscan discover changes in
      skeletal homeostasis, and can prevent severe disturbances and treat adequately
      those ones which already exist.

PMID- 8569602
TI  - Effect of calcium and 1,25 dihydroxyvitamin D on the level of parathyroid hormone
      in patients with secondary hyperparathyroidism due to chronic renal
      insufficiency.
AB  - Thirty-two patients with chronic renal insufficiency on the heamodialys were
      studied. Serum calcium significantly correlated with mPTH/iPTH ratio (p < 0.01).
      The rise in concentrations of calcium during calcium infusion significantly
      increased mPTH/iPTH ratio (p < 0.05). Concentrations of iPTH declined for more
      than 50% in 65% patients during calcium infusion. Secretion of PTH was not
      suppressed in two patients. Serum PTH values were lower in group of patients who
      received 1,25 dihydroxyvitamin D (p < 0.05). Serum calcium values were similar in
      these investigated groups. Suppression of PTH secretion with calcium rose in
      group of patients who received 1,25 dihydroxyvitamin D for two years. Suppression
      of PTH with calcium declined in two of three investigated patients who did not
      receive 1,25 dihydroxyvitamin D for two years.

PMID- 8569603
TI  - Hip scintigraphy in the diagnosis and evaluation of morbus Perthes.
AB  - During this research the role and significance of hip scintigraphy in diagnosis
      and evaluation of Perthes disease were examined. Three phase scan was applied in
      35 patients clinically suspected of Perthes' disease. There were no false
      positive findings in 20 patients who did not suffer from Perthes' disease and all
      15 who suffered from disease were scintigraphically positive. Our investigation
      confirmed clearly that late scintigraphy conducted with pinhole colimator can be
      used as a reliable method for diagnosis and evaluation of Perthes' disease.

PMID- 8569604
TI  - Significance of sacroiliac index in diagnostics of seronegative
      spondyloarthropathies.
AB  - Sacroiliac index (SI index) was determined by the quantitative scintigraphy in
      106 patients:28 with ankylosing spondilitis, 51 with Reiter's disease, 9 with
      psoriatic, 18 with unclassified seronegative spondylarthropathy and in 20
      controls. For the right joint, statistically significant difference was found
      between the control group SI-index value and the one in patients' group (p <
      0.001 to p < 0.005) except in patients with psoriatic spondylarthropathy.
      Analysing each group of patients separately, statistically significant difference
      between the SI index of both left and right joint was present only in the group
      with Reiter's disease (t = 2.08: p < 0.05). Increased SI-index was found in
      45.28% of all patients and this also confirmed sensitivity of the applied method,
      while the value of test specificity was 86.96%. Correlation between sedimentation
      rate and SI index as well as between radiographic finding and SI index was not
      present. There was a positive correlation between clinical findings and Reiter's
      disease but only in 56% of cases. It was concluded that scintigraphy is a useful
      but insufficient method in the diagnosis of seronegative spondylarthropathies.

PMID- 8569605
TI  - Treatment of rheumatoid arthritis with radionuclide combination.
AB  - Radiation synovectomy (RSIN) with radionuclide combination (N) was performed in
      135 patients with rheumatoid arthritis or 417 joints: 155 knee joints (90Y), 230
      MCF or PIF joints (169Er), 17 ankle, 7 wrist, 6 elbow and 2 shoulder joints
      (186Re). Therapeutic effect was followed up during 8 year period. After 3 years
      positive effect of the treatment was achieved in 70-80% of cases and complete
      treatment in 50-60% of cases, while 8 years later the same effects were
      maintained in 55-60%, i.e. 35-40% of the treated joints. The best effect was
      achieved in the treatment of the knee and the worst in the treatment of the wrist
      joint. At simultaneous application of one or several different RN, the total dose
      for one patient did not exceed 259 MBq while the maximum dose was 695 MBq during
      the long-term treatment.

PMID- 8569606
TI  - Salivary gland scintigraphy in patients with primary Sjogren's syndrome.
AB  - Methodology, interpretation and results of salivary gland scintigraphy in 33
      patients with primary Sjogren's syndrome (pSs) are presented. Patients were
      divided in two groups: 14 patients with isolated pSs and 19 patients with pSs and
      extraglandulary manifestations. There was no correlation between scintigraphic
      findings and duration of disease, and between scintigraphic findings and presence
      of recurrent swelling of parotid glands. The damage of salivary glands, detected
      by scintigraphy, was more marked in patients with pSs and extraglandulary
      manifestations than in patients with isolated pSs.

PMID- 8569607
TI  - Salivary excretory index--quantification of the ascorbic acid response in dynamic
      radionuclide sialography.
AB  - Dynamic radionuclide sialography (DRS) provides data about the aptitude of
      salivary glands to accumulate the tracer and to secrete the saliva. Visual
      interpretation of the t/a curves may be onerous when salivary glands uptake
      function is impaired. The purpose of the study has been to quantify the ascorbic
      acid (AA) response by means of salivary excretion index (SEI). DRS was performed
      in 10 healthy subjects and in 118 patients with various diseases of the parotid
      glands. Data acquisition (80 frames/15 s) started simultaneously with i.v.
      administration of 99mTcO4. Fifteen minutes later AA was given per os. Regions of
      interest were set over parotid glands. SEI was derived using the formula: SEI =
      (2b-a-c)/b, where a, b and c were cpm 3 minutes prior, in the moment when, and 3
      minutes after AA was given. In 9 of 10 controls SEI was greater than 55 (mean =
      63.2). Results in patients with Sjogren's and Mikulicz's syndrome and
      sialoadenitis, were significantly lower than in healthy subjects. Lowest results
      were found in patients with sialolithiasis. It may be concluded that SEI improves
      objective assessment of the AA response particularly in patients with minute or
      asymmetric disorders of salivary glands function.

PMID- 8569608
TI  - Estimation of the gallbladder motility after meal stimulation in the
      postgastrectomy patients by infusion cholescintigraphy.
AB  - The aim of this study is the assessment of the gallbladder (GB) motility in the
      controls without (C) and with (Cs) test-meal stimulation, as well as in the
      patients early (EPG) and late (LPG) after total gastrectomy. Data were collected
      with ROTA scintillation camera, during (3 h, 10 ml/h) infusion of 150 MBq, 0.25
      mg/ml 99mTc-EHIDA, preceded by a loading dose (0.5 mg/ml, 50 MBq). While in EPG,
      GB motility is impaired, it achieves physiological values in LPG patients, which
      can be attributed to establishment of corresponding hormonal mechanisms, in the
      late postoperative period.

PMID- 8569609
TI  - The evaluation of tumor markers levels in determination of surgical procedure in
      patients with gallbladder carcinoma.
AB  - In purpose of early diagnosis of gallbladder carcinoma, the serum levels of tumor
      markers CA 72-4, CA 19-9, CEA, AFP, Ferritin and beta HCG were determined in 124
      patients with benign and malign diseases of gallbladder, before and 10 days after
      the operation. The most important clinical significance have CA 72-4 and CA 19-9,
      which are increased in Ca in situ and carcinoma of the first stage. These early
      stages of carcinoma cannot be diagnostified by preoperative echotomography, but
      radical operation is possible with recover by all means. These two tumor markers
      should be attended in risk group of patients for rising gallbladder carcinoma:
      calculosis and polyposis. The rest of tumor markers are increased in progressive
      carcinoma with infiltration of surrounding tissue and metastases.

PMID- 8569610
TI  - Correlation between the blood pool tomoscintigraphy (SPECT) and planar
      scintigraphy in the diagnostic of the liver hemangioma.
AB  - The aim of the study was the estimation of diagnostic importance of the hepatic
      blood pool tomoscintigraphy (SPECT) and planar scintigraphy in patients
      investigated under suspicion of the liver hemangioma. In the diagnostic procedure
      the correlation between radiocolloidal scintigraphy, blood pool planar
      scintigraphy (early and late) and SPECT was made. Sixty-seven patients with focal
      lesions in the liver were investigated. The blood pool scintigraphy was made
      after application of traser dose of 99mTc and equilibration of tagged red blood
      cells in circulation. The planar scintigraphy was made 20 min after the red cells
      tagging and again 2 hours later (early and late scintigrams). SPECT was also
      applied to make the diagnostic procedure more accurate. From 31 hemangiomas
      detected by SPECT only 19.4% were clearly visible by planar scintigraphy. The
      diagnostic of very small hemangiomas is enabled by SPECT too.

PMID- 8569611
TI  - Determination of alpha-fetoprotein by radioimmunoassay. Improvement of the
      quality of a locally produced kit.
AB  - With the aim of improving the sensitivity and simplifying the analytical
      procedure, changes have been made in the test for determining alpha-fetoprotein
      (AFP) by radioimmunoassay, using a locally developed kit first produced about ten
      years ago. Close correlation between values obtained for serum AFP using the old
      and new procedures was obtained (r = 0.977), but the mean value for healthy
      nonpregnant adults was found to be 2.5 micrograms AFP/l with the new test. This
      is about half the level obtained earlier and confirms the recent findings of
      other authors. Besides reducing the time and equipment necessary for performing
      the test, the modified procedure enables more precise distinction between normal
      and elevated concentrations of AFP in patient serum.

PMID- 8569612
TI  - Determination of alpha-fetoprotein by radioimmunoassay. Ten year experience in
      applying a locally produced kit.
AB  - Increased concentrations of serum alpha-fetoprotein (AFP) occur in several
      physiological (pregnancy) and pathological (liver regeneration, tumour formation
      etc.) conditions. Measurement of serum AFP levels may assist in the detection of
      fetal abnormalities during pregnancy, in the detection of renewed tumour growth
      and metastases in cases of AFP producing tumours and in monitoring some diseases
      of the liver. In this paper some results are given concerning the follow-up of
      some patients with tumours of the testis and the possibilities of determining the
      source of elevated serum AFP (regenerating hepatocytes, malignant liver cells,
      hepatic metastases from other tissues) in patients with liver diseases.

PMID- 8569613
TI  - The importance of monitoring colorectal adenomas by tumor markers (ROC analysis).
AB  - Are the increased values of specific tumor markers significant in monitoring
      colorectal adenomas at the beginning of malignant alteration? Tumor markers (CEA,
      CA 19-9 and CA 72-4) were determined in sera by IRMA kits. The increased levels
      of tumor markers CEA and CA 19-9 were statistically very significant in patients
      (28) with colorectal adenomas at the beginning of malignant alteration and in the
      group with colorectal adenocarcinomas (96). By ROC analysis the sensitivities,
      positive predictive values and negative predictive values of CEA and CA 19-9 were
      quite acceptable with high accuracies for all determined tumor markers in
      colorectal adenomas at the beginning of malignant alteration. Those findings
      suggest the importance of monitoring of colorectal tumours and precancerouses by
      tumor markers serum levels and it confirms the usefulness of counting results by
      ROC analysis.

PMID- 8569614
TI  - Tumor markers in detection of metastases--illustration of some practical aspects.
AB  - Authors are presenting 5 cases where positive findings of tumor markers indicated
      additional examinations for previously established negative metastases detection.
      In all the cases metastases were confirmed by additional diagnostic procedures.
      Authors are pointing out that this is a matter to consider in oncological
      practice.

PMID- 8569615
TI  - The clinical use of 131I-meta-iodo-benzylguanidine (MIBG) for the diagnosis of
      neuroblastoma.
AB  - Whole-body scintigraphy with 131I-meta-iodo-benzylguanidine 131I-MIBG) was
      performed in 41 patients with neuroblastoma. In patients with clinical remission
      no pathological concentration of 131I-MIBG was found. In 30 patients with
      residual, recurrent or metastatic disease neuroblastoma was correctly localized
      by 131I-MIBG scintigraphy. It is concluded that 131I-MIBG whole-body scintigraphy
      is useful in the diagnosis and follow-up of neuroblastoma.

PMID- 8569616
TI  - Reevaluation of the results of iodine prophylaxis in eradication of endemic
      goiter in Macedonia.
AB  - In order to reevaluate effectiveness of iodine prophylaxis in Macedonia,
      epidemiological, ultrasonographic studies and estimation of urine excretion were
      performed. The results from the epidemiological survey in nongoitrogenic regions
      demonstrated goiter between 12.8% and 18%. Much higher prevalence of goiter was
      found in goitrogenic regions, between 20.8% and 60.8%. The incidence of goiter
      increased with age, and its prevalence is higher in girls when compared with the
      boys of the same age group. The thyroid volume estimated by ultrasonography was
      higher in children from goitrogenic regions when compared to nongoitrogenic.
      There was a good correlation between ultrasonographic volumetry data and size of
      the thyroid estimated by palpation. Urinary iodine excretion demonstrated low
      values in children from goitrogenic regions as indicator of iodine deficiency.

PMID- 8569617
TI  - Autoantibodies to triiodothyronine and thyroxine in primary hypothyreosis.
AB  - The role of autoantibodies to triiodothyronine and thyroxine hormones is still
      obscure. Our investigation of autoantibodies in primary hypothyreosis gave
      controversial results. We have investigated 40 patients with primary
      hypothyreosis caused by chronic atrophic thyroiditis and lymphocytic Hashimoto
      thyroiditis. We have examined autoantibodies to triiodothyronine (T3) and
      thyroxine (T4) in patients prior to and during substitution therapy. The control
      group of 50 subjects with no signs of thyroid gland disease were also examined.
      Positive antibodies to their own T3 or T4 hormones were not found in this group.
      Out of 40 patients with primary hypothyreosis, autoantibodies to their own
      hormones were found in 11 patients (27.5%). At the same time, antibodies to T3
      and T4 were found in 3 patients, antibodies to T3 in 7 and antibodies to T4 were
      found in only 1 patient. In the course of substitution therapy (L-thyroxine)
      there was an increase in number of patients with antibodies to T4, thus having no
      statistical significance in comparison with the total number of patients with
      positive antibodies to T3 and T4.

PMID- 8569618
TI  - TSH-receptors and prognostic value of their analysis.
AB  - TSH receptors were analyzed by equilibrium binding method of Scatchard in nodular
      and perinodular specimens surgically obtained from nine patients suffering from
      thyroid nodular goiter, which were clinically euthyroid. Among these patients,
      the group of those at "real risk" for reappearance of postoperative thyroid
      nodule in follow-up period was formed. The obtained results showed that there
      were no significant differences in specific 125I-bTSH binding between perinodular
      (assumed to be normal by PH analysis) and nodular tissues. The level of high
      affinity receptors was higher in perinodular than nodular specimens, while low
      affinity binding sites were increased in nodular tissue. Decreased level of high
      affinity and increased content of low affinity binding sites were observed in
      perinodular compared to nodular specimens obtained from patients of "real risk"
      group. These results give evidences for real risk of postoperative compensatory
      hypertrophy and thyroid goiter relapse in follow-up during long-term period.

PMID- 8569619
TI  - The frequency of thyrotoxicosis in war time period.
AB  - The frequency of thyrotoxicosis in peace and war time periods was compared in the
      same region with the same population. In one year peace and war time periods 54
      and 87 cases of thyrotoxicosis were found, respectively, which indicates the
      increase for 62%. The results point to the conclusion that psychic trauma
      increases the number of patients affected by thyrotoxicosis.

PMID- 8569621
TI  - Nuclear Medicine of Yugoslavia in 1992. Proceedings of a meeting. Sremska
      Kamenica, 30-31 October 1992.

PMID- 8569620
TI  - Usage of quantitative static scintigraphy of the thyroid gland in defining the
      therapeutical dose of radioiodine.
AB  - In a group of 21 patients sent by endocrinologist for antihyperthyreosis therapy
      with radioactive iodine, we calculated and compared the weight of the thyroid
      gland by quantitative static scintigraphy, using two computed parameters-
      according to surface and volume of the gland. Statistically we came to the
      conclusion that weight of the thyroid gland calculated on the basis of surface
      gives significantly higher values than calculation by the use of volume. The
      calculation of weight of the thyroid gland using the surface of scan image is
      recommended, while quantitative static scintigraphy increases the standardisation
      of the procedure very much.

PMID- 8569622
TI  - Protocol of the diagnostic, therapy and follow-up of differentiated thyroid
      cancer.
AB  - The Protocol of the multidisciplinary diagnostic treatment and follow-up of
      differentiated thyroid cancers, made in the Institute of Oncology in Sremska
      Kamenica, is described. It is in use in this institution from 1990. It is in
      concordance with general oncology principles and follows the guidelines of the
      International Union Against Cancer (UICC) concerning this problem.

PMID- 8569623
TI  - Glucocorticoid receptor quantification under low glucocorticoid level conditions.
AB  - Disturbances in the glucocorticoid hormone serum level lead to dramatic,
      frequently lethal changes in mammalian organism (Addison's disease, Cushing's
      syndrome). Hypofunction of adrenal glands (hypocorticism) was simulated by
      bilateral adrenalectomy of male Wistar rats. Changes in the liver cell
      glucocorticoid receptor (GR) content were followed throughout 2 hrs to 8 days in
      the postoperative period, by the quantitative Western blot method and by the
      synthetic steroid equilibrium binding method of Scatchard. The results of our
      measurements showed: 1, 1.5 to 2 fold increase in the rat liver GR protein of
      adrenalectomized animals in respect to the appropriate controls. 2. the increase
      in the GR protein occurs already 2 hours after the operation and remains at the
      increased, plateau values throughout the time period studied. It is suggested
      that the liver GR level may be regulated by the negative feed back mechanism. The
      raised GR level in adrenalectomy may be a functional adaptation to the low
      hormone conditions.

PMID- 8569624
TI  - Effects of insulin on the level of glucocorticoid receptors.
AB  - The investigation of insulin effects on the glucocorticoid receptor (GR) in
      cytosol fraction of rat liver has been done in order to bring about more evidence
      on the interaction of these hormones in the regulation of metabolic processes.
      The experiments were performed with male Wistar rats intraperitoneally injected
      by 25 micrograms of insulin/100g body weight 3 or 18 hours before analysis. The
      obtained results show that insulin induces time dependent changes, in both, the
      level and functional properties of GR. The significant increase in the binding
      activity and receptor content was observed in both analysed time intervals of
      insulin treatment, while these increases were higher after 18 hours of insulin
      administration. These evidences suggest that mechanisms of cooperative effects of
      insulin and glucocorticoid on regulation of cell function involve the modulation
      of hormone signals transmission through increase in level and/or functionality of
      receptor proteins.

PMID- 8569625
TI  - Determining the lifespan of platelets labelled with 111In oxinate--first results.
AB  - The paper presents the new method of platelet labelling, quality control of
      separation and labelling, as well as the investigation of the 111In oxinate
      labelled platelets lifespan. Among the 23 investigated persons, there were 4
      hematologically healthy persons and 19 ITP patients. Homologous and autologous
      labellings were done in one and 22 persons, respectively. Determination of the
      platelet lifespan in healthy subjects enabled the estimation of "in vitro"
      procedures of separation and labelling, as well as "in vivo" behaviour of the
      labelled platelets. Our results show that 111In oxinate labelled platelets have
      normal lifespan (8.9 +/- 0.6 days), which means that the procedure of separation
      and labelling does not damage them. In the ITP patients the platelet lifespan is
      shortened (0.4-4.6 days), which confirms the mechanism of thrombocytopenia. In
      the subject where homologous labelling had been done, we found out the existence
      of sensibilisation toward the donor platelets, which lead to the correction of
      therapy.

PMID- 8569626
TI  - [Position paper on propellants in measured dose aerosol dispensers. The German
      Respiratory League].

PMID- 8569627
TI  - [How often is thrombolytic therapy of deep pelvic-leg venous thrombosis
      indicated?].
AB  - BACKGROUND: For patients with deep vein thrombosis new thrombolytic regimes are
      being proposed and demand evaluation in controlled studies. We tested
      prospectively, how many patients in internal medicine are candidates for
      thrombolysis. PATIENTS AND METHODS: All available patients with the diagnosis of
      deep vein thrombosis (DVT) in lower extremities who were admitted to the service
      of internal medicine in a medium-sized hospital during one year were
      prospectively evaluated for the indication of fibrinolysis therapy according to
      the established criteria. RESULTS: A total of 62 patients were enrolled.
      Fibrinolysis was not proposed in 25 patients aged over 70 years nor in another 9
      patients in whom the thrombosis was restricted to calf veins. Nine additional
      cases had a recurrence of DVT (n = 4) or a history of more than 14 days. Among
      the remaining 19 patients, fibrinolysis was not performed in 11 because of
      advanced malignomas (n =4) or other diseases (n = 3) with limited life
      expectance, enhanced probability of haemorrhage (n = 3) and obvious non
      compliance (n = 1). Eight patients were offered thrombolytic therapy, but 5 of
      them denied consent after being comprehensively informed. CONCLUSION: Obviously
      by far most of patients admitted to internal medicine for DVT are candidates for
      standard heparin therapy only.

PMID- 8569628
TI  - [Findings in 100 patients with idiopathic increase in serum creatine kinase
      activity].
AB  - BACKGROUND: In outpatient clinics for neuromuscular diseases sometimes patients
      are presented because of an raised activity of the serum creatine kinase (CK)
      activity, accidentally detected. The purpose of this study was to investigate,
      how many patients with an unexplained hyperCKemia really suffer from a
      neuromuscular disease, and to present an adequate procedure for evaluating
      pathological CK activities. PATIENTS AND METHODS: In this retrospective study,
      clinical, electromyographic and myopathological findings of 100 consecutive
      patients (38 women and 62 men, aged 19 to 78 years) with such an abnormality of
      unknown origin are presented. RESULTS: Only 41 patients really had no muscular
      troubles and no signs of neuromuscular disorders at physical examination. The CK
      of 12 patients turned to normal at follow-up examination. In 4 patients a so
      called makro-CK was found. In 50 patients, in-depth examinations including a
      muscle biopsy were performed. In 10 patients, the increased CK-activity could be
      attributed to a complication of an already known basic disease, e.g., by
      confirming a myositis in case of proven connective tissue disease. In 14 patients
      an independent muscle disease was proven: 3 degenerative, 5 metabolic or
      mitochondrial as well as 4-inflammatory myopathies. In 2 patients, a secondary
      myopathy in polyneuropathy was suspected to be the etiology of the increased CK
      activity. In 9 patients, well treatable disorders were discovered. In 34
      patients, no muscle biopsy was performed and follow-up examinations were
      recommended. The ratio of the clarified diagnoses did not depend on the level of
      the CK activity. CONCLUSION: Every hyperCKemia indicates a thorough internal and
      neurological examination independently from the level of the enzyme activity. A
      scheme for examination in case of abnormal CK activity is proposed.

PMID- 8569629
TI  - [Sumatriptan--side effects and problems in routine clinical practice].
AB  - AIM: The study tried to investigate the efficacy, adverse events and possible
      risk factors of sumatriptan in daily clinical practice. PATIENTS AND METHODS: 72
      outdoor patients, who had treated their headaches at least once with sumatriptan,
      partly prescribed to them by outdoor physicians, were asked about their
      experiences with the drug. According to the criteria of the International
      Headache Society (1988) 55 patients were suffering from migraine, 11 from cluster
      headache and 6 from tension-type headache. RESULTS: Migraine and cluster patients
      rated the drug as effective as described in literature. Adverse events were
      reported by 69% of the patients which was more frequent than in most clinic
      studies described. Adverse events were usually not serious and transient. They
      were reported significantly more often by migraine patients than by patients with
      cluster headache and might not all be correlated to the therapy of sumatriptan.
      CONCLUSION: Sumatriptan has shown to be effective in the treatment of an acute
      migraine- and cluster-headache. The risk as to severe adverse events, especially
      cardial adverse events, exists if contraindications for sumatriptan are not
      considered. Sumatriptan should therefore only be prescribed to carefully
      diagnosed migraine and cluster headache patients. It should, however, not be
      given to patients suffering from drug abuse, because they might just change over
      to sumatriptan.

PMID- 8569630
TI  - [Ascites with a blind spot].

PMID- 8569631
TI  - [Mass screening for the prevention of colorectal carcinoma].

PMID- 8569632
TI  - [Prevention of osteoporosis--why? Who? How?].

PMID- 8569633
TI  - [Differential internal medicine diagnosis of uveitis].

PMID- 8569634
TI  - [Prions].

PMID- 8569635
TI  - [Prions--pathogens of transmissible dementia in the human].

PMID- 8569637
TI  - [Evolution of child nutrition in the 20th century].

PMID- 8569636
TI  - [Follow-up of malignant metastatic pheochromocytoma. Discussion of the
      therapeutic strategy].

PMID- 8569638
TI  - [Cognitive and affective characteristics of children with malformation syndrome].
AB  - The aim of this paper is to study the psychological and relational aspects in
      children suffering from specific malformative syndrome and precisely Down s.,
      Sotos s., X-Fragile s. and Williams s. Indeed literature provides much data
      related to the phenotype, to the organic-biological characteristics, but little
      or nothing is known about the affective structure, the episodes and to the
      particular dynamics that emerge in he relation between the parents and the
      malformed child. A protocol was applied to our sample group (16 subjects). This
      protocol includes laboratory and instrumental tests (chromosome test,
      neurometabolic screening, EEG, CT or cranial MRI, cardiac and abdominal
      ultrasonography, ear and eye test) aspects. This evaluation is carried out
      through the proposal of standardized situations (psychometric tests) and a use of
      a freer observational setting. This permits us to understand how the child
      perceives himself the awareness and the image he has of himself and how able he
      is to integrate his illness experiences and his way of relating with the
      environment. The data of our observations are thus used to compile a grill for
      the structural diagnosis of the personality. Besides, this evaluation is flanked
      by the observation of the family in order to explore the psychological image that
      parents have of their child, his character, his good points, his bad points, his
      similarities, how he relates to them, any educational problems and the emotional
      reaction that the communication of the diagnosis has raised in them. The
      videotaped observations are subsequently evaluated through the application of a
      grill for the study of the mother-child relationship. The results obtained from
      the psychological research underline a reasonable heterogeneity both of the
      intellectual level and of the metapsychological profile. Twelve subjects were
      mentally retarded (5 with mild mental retardation, 7 with moderate mental
      retardation); the remaining 4 had a normal cognitive development (3 with Sotos
      s., 1 with Williams s.). Psychological disturbances are present and thus divided:
      light disturbances (affective immaturity, neurotic-depressive organisation) in 11
      subjects. Average disturbances (dysharmonious structure, and borderline
      personality) in 4 subjects; severe disturbances (psychosis) in 1 subject.
      Besides, above all in the group of subjects with X-Fragile s. and Down s., the
      tendency to assume behaviour of a regressive type, also postural, emerges. Among
      the 4 groups it is frequent to resort to defence mechanisms of hypomaniac type,
      accompanied by the denial of the patient's "sick parts". Another common
      characteristic concerns the quality of imaginary life which is shown to be
      repetitive and stereotype in content. Indeed these children's play activity
      characterized by a limited capacity of symbolization. Instead, when the symbolic
      process is more developed, contents concerning a deteriorated and destructive
      image of the Self emerges. Through the evaluation of family dynamics what is more
      noticeable is that the parent-malformed child interaction appears to be quite
      nonstimulating and noninvolving or incoherent, lacking in harmony and empathy
      towards the child's inner world. Indeed we can notice a lack of both verbal and
      extraverbal exchange of communication and brief interactive sequences which do
      not usually take into account the child's proposals and an affective tonality of
      depressive and nonaffective type. Therefore it may be concluded a certain
      smoothness in the clinical expression of the syndromes considered, both as far as
      the cognitive deficit entity and the psychic problems are concerned. Referring to
      the interactive dynamics between parents and children with dismorphic syndrom it
      seems that the child's pathology becomes the organizational summit of the above
      mentioned relational dynamics among most of the patients examined...

PMID- 8569639
TI  - [Apparent life threatening events (ALTE): prelude to SIDS? Description of 14
      cases].
AB  - The peak incidence of the Sudden Infant Death Syndrome (SIDS) is between 2 and 4
      months of age. Its pathology is extremely heterogenous, infection, hypoxia and
      many others factors are all implicated. We examine here the possible relation
      between SIDS and Apparent Life Threatening Event (ALTE). We describe 14 cases
      that we have observed to establish a primary connection between these two
      situations and to identify a risk-group for an accurate follow-up.

PMID- 8569640
TI  - [Sequelae of bacterial meningitis in childhood: a study of hearing impairment].
AB  - Bacterial meningitis is an infection of the central nervous system involving
      quite a number of neurological sequelae the most common of which is hearing
      impairment. To assess the incidence of audiological deficit the authors evaluated
      retrospectively 20 patients, between 4 months and 11 years of age, observed at
      the Pediatric Clinic at the University of Pisa between 1988 and 1993. A clinical
      neurological examination and a complete auditory assessment (using BAEPs and
      impedence audiometry) has been performed in every patient between 1 and 18 months
      after they left hospital. 4 children had persisting neurological sequelae, 3
      patients developed sensorineural hearing loss and one child visual impairment and
      seizures. Haemophilus Influenzae was responsible for 2 cases of sequelae and
      Streptococcus Pneumoniae for the other 2 cases. The number of days of illness
      before hospitalization and the institution of an antibacterial treatment,
      persistence of fever and deviation from the normal level of consciousness and
      persistence of neck rigidity were not correlated with the presence of sequelae.
      No correlation has been found between sensorineural hearing loss and the kind of
      antibacterial therapy. It's advisable that every child, following bacterial
      meningitis, should undergo a complete and repeated audiological assessment to
      detect any lesser impairments and/or unilateral losses that may damage the
      development of speech and language in any way.

PMID- 8569641
TI  - [Chronic bullous dermatoses of childhood in the differential diagnosis of bullous
      dermatitis in children].
AB  - We report a case of chronic bullous dermatosis of children, a benign dermatologic
      disease of infancy of unknown etiology, characterized, on IIF, by linear deposits
      of immunoglobulins in the Basement Membrane Zone of cutis, and clinically by a
      ring shaped disposition of bullae (rosette-like). This work concerns a ten year
      old girl admitted to the pediatric ward at E. Agnelli Hospital of Pinerolo
      (Turin) about one year ago, who started having perioral bullous eruption,
      subsequently spread all over the body skin, with general symptoms of fever and
      itching. Round erythematous plaques, crusts, and a ring disposition of sausage
      shaped subepidermal bullae were suggestive of CBDC. Diagnosis was confirmed by
      cutaneous biopsy and DIF. Corticosteroids, given for about six mths., and DDS in
      the last four mths. of treatment, quickly changed the course of the disease,
      which has not recurred for about one year. Differential diagnosis with other
      bullous dermatoses of 2nd and 3rd childhood has been addressed to bacterial and
      viral diseases as well as to toxico-allergic and autoimmune diseases, the latter
      rarely seen by Pediatricians. Among those we discuss on clinical and
      anatomopathological aspects of Dermatitis herpetiformis, Erythema multiforme,
      Pemphigus and Pemphigoid, with regard to different anatomic sites of bullous
      lesions and to pathogenesis involved immunoglobulins and skin antigens.

PMID- 8569642
TI  - [Mammary duct ectasia in children].
AB  - Authors describe two uncommon cases of infantile mammary duct ectasia (EDM). This
      disease, first reported in 1983, is characterized by dilatation of the subareolar
      duct system, and by phlogistic reaction and fibrosis. In the medical literature
      only 8 cases have been reported, but probably its frequency is undervalued due to
      the scarce general knowledge of this pathology. The differential diagnosis is
      reviewed.

PMID- 8569643
TI  - [Cardiofacial syndrome. A case report].
AB  - A case of cardio-facial syndrome with dysmorphic and asymmetric crying face,
      congenital heart defects, failure to thrive is described. The authors review the
      literature and underline the importance of asymmetric crying face as a marker of
      associated congenital anomalies.

PMID- 8569644
TI  - Effect of inhaled nedocromil sodium therapy on blood gas changes in children
      challenged with ultrasonically nebulized distilled water. A comparison of 8 mg
      versus 16 mg daily dose.
AB  - Changes in time course of blood partial pressures of oxygen (PtcO2) and carbon
      dioxide (PtcCO2) before, during and after challenge with ultrasonically nebulized
      distilled water (UNDW) were evaluated in 22 children with mild asthma in basal
      conditions, and after 8 weeks of therapy with inhaled nedocromil sodium at a
      daily dosage of 8 or 16 mg. PtcO2 and PtcCO2 were followed using transcutaneous
      O2 and CO2 monitoring system. All asthmatic subjects presented a significant
      decrease in PtcO2 and/or PtcCO2 (> 20% basal value) during or after challenge.
      After therapy, the decrease in PtcO2 and PtcCO2 was normalized in the group
      treated with 16 mg/day, whereas only a partial yet significant reduction in the
      decrease of O2 and CO2 was observed in the group assuming 8 mg/-day. These data
      indicate that inhaled nedocromil is effective in treating bronchial
      hyperresponsiveness in childhood and that the dose required to achieve this
      effect is of 16 mg/day.

PMID- 8569645
TI  - [Significance of lactose breath test in the newborn].
AB  - Lactose breath test have been performed in healthy newborns, in whom breath
      hydrogen excretion was preliminarily demonstrated by lactulose breath test. 27.5%
      of newborns showed positive lactose breath test, with no differences related to
      sex and gestational age, while a higher percentage of positive test has been
      found in < 2500 g and formula-fed neonates compared, respectively, to > or = 2500
      g and breast-fed ones. In healthy newborns, without any clinical signs of lactose
      intolerance, it is possible to demonstrate hydrogen in expired air; this is not
      equivalent of lactose malabsorption, but, instead, depends on the phenomenon of
      colonic fermentation that allows energy and nutrient absorption.

PMID- 8569646
TI  - Out of the classroom--into the exam room.

PMID- 8569647
TI  - University of Minnesota community rotations expose students to family practice.

PMID- 8569648
TI  - Retirement of senior physicians in rural Minnesota. Factors influencing
      physicians' plans to retire.
AB  - The demand for physicians in rural Minnesota is likely to increase significantly
      over the next few years. Nearly 20% of all rural physicians in Minnesota are
      older than age 65. This paper reports the results of a survey of rural Minnesota
      physicians over age 60 on their current practices and their plans for retirement.
      Of the 33 physicians questioned, 25 (75%) currently had plans to retire and more
      than half of the 25 planned to retire in the next two years. Factors that these
      physicians perceived as important in determining their decisions to retire or
      continue practice are described, and implications for the delivery of health care
      in rural communities are discussed.

PMID- 8569649
TI  - Life after medical practice. A retirement profile of Minnesota physicians.
AB  - This study investigates the current dynamics of physician retirement in
      Minnesota. A survey of all retired Minnesota physicians (878, with 65.7% response
      rate) revealed that 73% retired in their 60s, 22% at age 65. Good health was
      reported by 69% of the respondents, and fair health by 26%. Income was sufficient
      in most cases; 64% of respondents reported living comfortably, and only 14% said
      their incomes are barely adequate. The study also showed that retired physicians
      consider nonmedical activities much more important than medical activities;
      heading the list were visiting family (86%), reading (79%), and travel (63%).
      Finally, 35% of respondents found retirement to be better than they had expected,
      54% found it about as expected, and only 9% felt retirement was not as good as
      expected. In retirement, Minnesota physicians are generally healthy, have
      sufficient funds to live comfortably, and generally spend their time doing
      nonmedical activities.

PMID- 8569650
TI  - Laparoscopic-assisted hysterectomy in a rural Minnesota hospital.
AB  - Hysterectomy remains a commonly performed gynecologic surgery. An estimated
      650,000 women in the United States undergo surgical removal of the uterus
      annually at a considerable cost to patients, payers, and society at large.
      Currently, two-thirds of hysterectomies are performed by abdominal surgery and
      approximately one-third by vaginal surgery. Most research supports laparoscopic
      assisted hysterectomy as a safe, effective, and less intrusive alternative to
      open surgery. Laparoscopy is far less costly, results in less pain, and has a
      much shorter recovery period. This paper discusses such advantages of the
      laparoscopic approach over the standard abdominal hysterectomy and reviews 158
      laparoscopic-assisted hysterectomies performed at a 100-bed rural Minnesota
      hospital. Techniques, equipment, patient mix, and complications are discussed.
      Patients experienced few complications, and most left the hospital in 48 hours.

PMID- 8569651
TI  - MMA calls for geographic equity in Medicare bill.

PMID- 8569652
TI  - Minnesota will lose federal Medicaid money.

PMID- 8569653
TI  - Medicare supplement plan required to cover diabetes.

PMID- 8569654
TI  - Three to get ready: taking EDI from theory to reality.

PMID- 8569655
TI  - Teaching by example.

PMID- 8569656
TI  - May the balance be with you.

PMID- 8569657
TI  - The biological basis of mental illness.
AB  - Belief in the biological roots of mental illness will govern some of what we do
      in a psychiatric rehabilitation program.

PMID- 8569658
TI  - The rehabilitation relationship.
AB  - A special member-staff relationship is necessary for psychiatric rehabilitation
      to be effective.

PMID- 8569659
TI  - Roots, fundamental ideas, and principles.
AB  - Agency history, basic principles, and attitudes influence a comprehensive version
      of psychiatric rehabilitation.

PMID- 8569660
TI  - Core programs in the thresholds approach.
AB  - Six goals guide the organization and implementation of a basic program of
      psychiatric rehabilitation.

PMID- 8569661
TI  - Special programs for special groups.
AB  - Special groups of persons with mental illness require individually tailored
      programs.

PMID- 8569662
TI  - Program evaluation and research at thresholds.
AB  - Threshold's degree of success in meeting its six program goals has been
      consistently evaluated and researched for many years.

PMID- 8569663
TI  - Organizational issues.
AB  - A strong organizational and decentralized administrative philosophy is is the
      underpinning of growth, program development, and quality.

PMID- 8569664
TI  - Current challenges.
AB  - An array of emerging issues in psychiatric rehabilitation do not get enough
      discussion.

PMID- 8569665
TI  - [Diagnosis of narcolepsy-cataplexy: importance of continuous recording in
      ambulatory EEG. Report of 20 cases].
AB  - Ambulatory EEG (A-EEG) allows longterm polygraphic recording over 24 hours or
      more and proves to be particularly useful in the diagnosis of narcolepsy
      cataplexy (N/C). We performed A-EEG using the Medilog 9000-8 channel system over
      a total of 36 24-hour periods in 20 consecutive N/C patients and recorded an
      average of 3.5 daytime sleep episodes, of which 2.2 were with SOREMP, AND 21
      evening SOREMP (58%). A MSLT was performed using A-EEG in 16 cases. Continuous A
      EEG proved to be more informative than the MSLT, and may represent a valid
      alternative to the classic continuous polygraphic recordings performed in the
      sleep lab, that are more cumbersome and costly. Although a full-night
      polysomnographic recording is still necessary whenever other sleep disorders are
      suspected in association with N/C, A-EEG is a first-line, practical method for
      the confirmation of N/C, which remains a clinical diagnosis.

PMID- 8569666
TI  - [Trypanosomiasis: determination of groups of patients from clinical and
      electroencephalographic data].
AB  - Data constituted from clinical and waking electroencephalographic signs in 104
      patients at meningoencephalitis stage of trypanosomiasis were treated by way of a
      correspondence analysis in order to determine clinical profiles. Three profiles
      were identified. The first one, encountered in patients with minor clinical
      disturbances and slightly modified waking electroencephalographic patterns is
      suggestive of a cerebral involvement stage onset. The second one, observed in
      patients with vigilance disturbances, behavioral and motor impairment, and highly
      abnormal EEG tracing is indicative of a more severe encephalitis stage. The third
      one, obvious in patients with EEG sharp waves organized in a more or less
      recurring fashion and accompanied by epileptic seizures is consistent with an
      acute cerebromeningitis.

PMID- 8569668
TI  - Contracting with managed care.

PMID- 8569667
TI  - [Interindividual variability of exogenous and endogenous auditory evoked
      potentials in a condition of voluntary attention].
AB  - The use of P300 in psychopathology raises the important problem of the
      constitution of reference normative data and of the high variability of auditive
      ERP's in controls. To handle better this problem, we recorded 86 control
      subjects, using an auditory oddball paradigm with motor response. We analyzed the
      successive components of the ERP's evoked by target and standard stimuli (N1, P2,
      N2, P3a, P3b and slow wave negativity). Our results underlined the role of age,
      sex and psychological factors on the ERP's interindividual variability: P3
      amplitude decreased and its latency increased with age, while its topography was
      more frontal in the older than in the younger subjects. The P300 occurrence after
      standard stimuli and P3 amplitude after target stimuli were different according
      to sex. Moreover, P300 amplitude, latency and topography were related to the
      subject's anxiety level. Finally, our results also propose new description modes
      of ERP's relying on P3a and P3b relative peak amplitude (P300 with prominent P3a
      or P3b), topographical predominance (frontal or parietal P300) and duration of
      the late positive complex (brief or long-lasting P300). These data will improve
      the clinical use of P300.

PMID- 8569669
TI  - BRIDGE: a community-based advocacy program for battered women in the emergency
      department.

PMID- 8569670
TI  - What can physicians do to help victims of domestic violence?

PMID- 8569671
TI  - Prostate cancer incidence in Missouri: an updated analysis.
AB  - Prostate cancer incidence increased dramatically in Missouri in the 1990s.
      However, this study demonstrates that the increased incidence parallels the
      dramatic increase in the earliest stage of the disease. Increased detection for
      prostate cancer is believed to play a strong role in this rising incidence.
      Continued surveillance for prostate cancer is necessary to determine the
      significance of the sharp rise in the incidence in Missouri.

PMID- 8569672
TI  - Radiation therapy in the treatment of localized prostate cancer: an alternative
      to an emerging consensus.
AB  - Optimal treatment for patients with localized carcinoma of prostate is
      controversial. Radiation therapy is an established modality; reports indicate
      that results are comparable to those of radical prostatectomy. A retrospective
      review was carried out of 963 patients with carcinoma of the prostate treated
      with definitive irradiation (65 to 71 Gy in 6.5 to 7 weeks). Survival, incidence
      of local recurrence and distant metastases, and postirradiation PSA data were
      analyzed. Ten-year disease-free survival with external irradiation was 100% for
      clinical stage A1 (T1a), 69% for stage A2 (T1b,c), 57% for clinical stage B (T2),
      and 41% for stage C (T3). Initial PSA level closely correlated with probability
      of freedom from chemical failure (PSA elevation) after definitive irradiation in
      317 patients with stage T1b,c and T2 tumors (96% and 89%, respectively, with
      initial PSA of < 10 ng/ml and 75% and 65% with higher PSA levels). Although
      modern irradiation techniques produce results comparable to those of radical
      prostatectomy in localized prostate carcinoma, we must continue to critically
      assess treatment policies, develop appropriately designed prospective clinical
      trials, and define optimal management of these patients.

PMID- 8569673
TI  - Early clinical experience with percutaneous cryosurgical ablation of the
      prostate.
AB  - In 1993 we started offering transrectal ultrasound-guided percutaneous
      cryosurgical ablation of the prostate (PCAP) as a treatment alternative for
      localized prostate cancer. Through 1994, 85 patients underwent PCAP and 53 had 3
      6 month postoperative biopsies. A learning curve effect was observed: 46% of
      early patients had positive postoperative biopsies, versus only 9% of later ones.
      With repeat PCAP on the early patients, currently 87% of the biopsied patients
      are disease free. While longer follow-up is necessary, it appears that PCAP
      merits further investigation as a treatment alternative for localized prostate
      cancer.

PMID- 8569674
TI  - [Immunohistological evaluation of esophageal cancer with antikeratin monoclonal
      antibodies].
AB  - In this study, I investigated the molecular weights of keratin-subunits in the
      tissue of esophageal cancer by enzyme-labeled antibody technique with four kinds
      of antikeratin monoclonal antibodies with different spectrums of reacting keratin
      subunits. Further more, the correlation between the molecular weights of keratin
      subunits and clinicopathological factors was evaluated, and that between the
      molecular weights and the prognosis was studied also. The positive rates of four
      kinds of primary antibodies did not correlate to clinical feature or prognosis,
      and each primary antibody showed different attitude regarding correlation to
      histopathological factors. I analyzed the molecular weights of keratin-subunits
      increased in the carcinoma tissue by the difference of staining intensities of
      four monoclonal antibodies. The histological findings of the cases with carcinoma
      tissues in which 48, 56 kd keratins increased were in high malignancy compared
      with other groups, and their prognosis was significantly poor. Examination of
      prognostic factors with multivariate analysis revealed that the increase of 48,
      56 kd keratins in the carcinoma tissues was the most important determining factor
      of prognosis next to lymphatic invasion.

PMID- 8569675
TI  - [An immunohistochemical study on microtubule associated protein-1 of normal and
      malignant human gastric tissue].
AB  - Microtubule Associated Protein-1 (MAP-1) plays an important role for
      polymerization of tublin to microtubules. Indirect immunohistochemistry using
      anti-MAP-1 monoclonal antibody was performed in this study. Difference of
      internuclear MAP-1 staining patterns between normal and malignant human gastric
      tissues was investigated. Normal gastric tissue had localized MAP-1 positive
      staining nucleus in corresponding area of generative cell zone of gastric gland.
      On the other hand, the 75% cases of gastric cancer showed numerous labeled nuclei
      in most of the cancer tissues, and 25% cases did not show positive staining of
      nuclei in cancer tissue. The nuclei staining were classified as negative (-),
      weak granular (+) and strong punctate (++). The tissue staining pattern was
      fallen into two patterns, uniform and ununiform stained groups. Positive nuclei
      staining for MAP-1 and staining pattern had no correlation with histological type
      of gastric cancer, vessel invasion and lymph node metastasis. But post operative
      5-years survival rares were 77.3% in uniform stained group and 30.0% in ununiform
      stained group. Thus, there were relationship between the post operative survival
      ratio and the staining pattern of nuclei. Internuclear MAP-1 staining pattern was
      considered to be one of effective parameters on prognostic sign in gastric
      cancer.

PMID- 8569676
TI  - [Experimental studies on endocrine therapy for rat hepatocellular carcinoma].
AB  - Androgen receptor (AnR) and estrogen receptor (ER) are known to exist in human
      hepatocellular carcinoma (HCC), but the low binding capacity casts doubts on the
      efficacy of endocrinotherapy. However, we focussed on the favorable dissociation
      constant and displacement of AnR and ER. Efficacy of endocrinotherapy for HCC was
      investigated using rat HCC cell line (AH66F) resembling the properties of human
      HCC and sex hormone receptors. In rat HCC AH66F, we confirmed that the AnR and ER
      were both positive and were mentioned binding capacity, dissociation constant and
      displacement resembled those of human HCC. In rat HCC AH66F, administrations of
      Tamoxifen converted AnR and ER responses to negative. Rat HCC AH66F was
      transplanted intraperitoneally to Donryu rats, various endocrinotherapies
      administered and the number of survival days compared with a control group. In
      male and female rats, the number of survival days was both in the orchidectomied
      (p < 0.01) and the Tamoxifen treated (p < 0.001) group significantly prolonged.
      However, in the group treated with medroxyprogesterone acetate no significant
      differences were observed. Also, in experiments with AnR (-) and ER (-) rat HCC
      cell line AH60C all endocrinotherapies were ineffective. Above results confirmed
      the efficacy of endocrinotherapy for rat HCC with positive sex hormone receptors.

PMID- 8569677
TI  - [Parathyroid transplants in dogs].
AB  - Autotransplantation of the parathyroid glands by mincing method has been
      performed to maintain parathyroidal function in patients with thyroid cancer,
      following total thyroidectomy and parathyroidectomy. The functional recovery of
      grafted parathyroid glands was studied in matured mongrel dogs histologically and
      by determining the PTH level and serum P, Ca, and compared three different forms
      of implant; whole gland, minced parathyroid tissue, and thick slices. The minced
      parathyroid tissue and thick slices were found to be far superior histologically,
      and endocrinologically, to the whole gland type of implant, with successful
      takes. And between two types of implants minced tissue and thick slices, no
      difference was observed histologically and endocrinologically. On the other hand,
      it is necessary for shortening the time to prepare implant tissue to get
      successful reimplantation. The time to prepare minced tissue is very short in
      comparison with thick slices. Thus our method (minced tissue) is very useful for
      successful reimplantation of the parathyroids.

PMID- 8569678
TI  - [Coronary artery disease in patients with abdominal aortic aneurysm].
AB  - To evaluate the influence of coronary artery disease (CAD), we reviewed 102
      patients who underwent elective repair of abdominal aortic aneurysm (AAA) between
      1982 and 1992. Prior to surgery, all patients underwent clinical evaluation for
      the presence of CAD including dipyridamole thallium scintigraphy. They were
      classified into the following groups: Group I (n = 66), no clinical evidence of
      CAD; Group II (n = 26), clinical evidence of stable CAD; Group III (n = 10),
      unstable CAD. Coronary angiography (CAG) was performed in group II and group III
      patients only. All patients in group I and group II underwent elective repair of
      their AAA without coronary revascularization. Eight patients in group III
      underwent CABG followed by elective AAA repair within two months. One of two
      patients who had impending ruptured AAA underwent combined CABG and AAA repair as
      a single operation and the other underwent AAA repair followed by CABG. One case
      of perioperative myocardial infarction occurred in group II, but there was no
      early postoperative death related to cardiac disease in group I and II. In group
      III, however one patient who underwent combined surgery died of low-output
      syndrome in the early postoperative period, no death or myocardial infarction
      occurred following staged operation in the other nine patients. This present
      results support the contention that CAG is not necessary in all AAA patients, and
      that they can be managed according to appropriate risk by a selective approach
      based upon clinical assessment of their CAD. It is also apparent that a staged
      operation can be performed very safely in patients with unstable CAD.

PMID- 8569679
TI  - Mutational analysis of the RNase-like domain in subunit 2 of fission yeast RNA
      polymerase II.
AB  - Local sequence similarity exists between the subunit 2 of eukaryotic RNA
      polymerases II and the barnase-type bacterial RNases. The RNase-like domain from
      the Rpb2 of Schizosaccharomyces pombe was expressed in Escherichia coli as a GST
      fusion protein and examined for its RNase activity. When the GST fusion protein
      was incubated in vitro with 32P-labeled RNA, the RNA degradation activity was
      less than 0.1%, if any, of the level of synthetic barnase. In order to check the
      in vivo function of this region, we constructed two mutant rpb2 alleles,
      rpb2E357A and rpb2H386L, each carrying a single amino acid substitution at the
      site corresponding to one of the three essential amino acid residues forming the
      catalytic site in barnase (mutation of barnase at the corresponding sites results
      in complete loss of RNase activity) and five other mutant rpb2 alleles, each
      carrying a single mutation at various positions within the RNase-like domain but
      outside the putative catalytic site for RNase activity. When these mutant rpb2
      alleles were expressed in an rpb2-disrupted S. pombe strain, all the mutants grew
      as well as the wild-type parent and did not show any clear defective phenotypes.
      These results suggest either that the RNase-like domain in Rpb2 does not function
      as an RNase in vivo or that the RNase activity of this domain, if present at all,
      is not essential for cell growth.

PMID- 8569680
TI  - Mutational analysis of the C-terminal region of AREA, the transcription factor
      mediating nitrogen metabolite repression in Aspergillus nidulans.
AB  - In Aspergillus nidulans the positive-acting, wide domain regulatory gene areA
      mediates nitrogen metabolite repression. Previous analysis demonstrated that the
      C-terminal 153 residues of the areA product (AREA) are inessential for at least
      partial expression of most genes subject to regulation by areA. Paradoxically,
      areAr2, a -1 frameshift replacing the wild-type 122 C-terminal residues with a
      mutant peptide of 117 amino acids, leads to general loss of function. To
      determine the basis for the areAr2 mutant phenotype, and as a means of
      delineating functional domains within the C-terminal region of AREA, we have
      selected and characterised areAr2 revertants. Deletion analysis, utilising direct
      gene replacement, extended this analysis. A mutant areA product truncated
      immediately after the last residue of the highly conserved GATA (DNA-binding)
      domain retains partial function. The areAr2 product retains some function with
      respect to the expression of uaZ (encoding urate oxidase) and the mutant allele
      is partially dominant with respect to nitrate reductase levels. Consistent with
      the areAr2 product having a debilitating biological activity, we have
      demonstrated that a polypeptide containing both the wild-type DNA-binding domain
      and the mutant C-terminus of AREA2 is able to bind DNA in vitro but no longer
      shows specificity for GATA sequences.

PMID- 8569681
TI  - The molecular nature of mutations in the mt A-1 gene of the Neurospora crassa A
      idiomorph and their relation to mating-type function.
AB  - The 293-amino acid mt A-1 ORF of the A mating-type idiomorph of Neurospora crassa
      is multifunctional. It confers A mating identity and is responsible for
      heterokaryon incompatibility. The goal of this study was to dissect the
      functional regions of mt A-1. New mutants of mt A-1 selected for loss of the
      incompatibility function were obtained. One new mutant, A(m)99, was partially
      fertile as a maternal parent. This is the first time that fertility and
      incompatibility functions have been separated for the A idiomorph. In this
      mutant, the mt A-1 ORF is truncated after the first 85 amino acids, indicating
      that this N-terminal region is minimally sufficient for female fertility. A
      series of deletion constructs and frameshift alleles of mt A-1 was obtained and
      tested for male-mating activity and vegetative incompatibility in transformation
      experiments. These experiments showed that a region from position 1 to 111 is
      sufficient to confer incompatibility, while amino acids from position 1 to 227
      are required for mating activity. A transcriptional analysis of mt A-1 showed
      that the mRNA is expressed both before and after fertilization. This, together
      with the phenotype of the A(m)99 mutant, suggests a post-fertilization function
      for mt A-1.

PMID- 8569682
TI  - Mapping of the nucleolus organizer region on chromosome 4 in Arabidopsis
      thaliana.
AB  - In Arabidopsis thaliana the ribosomal RNA genes (rRNA genes or rDNA) are
      clustered in tandemly repeated blocks in two nucleolus organizer regions (NORs).
      Cytogenetic analysis has shown that the NORs are localized on chromosome 2 (NOR
      2) and 4 (NOR 4). Recently the map position of NOR 2 was determined using a RFLP
      which was larger than 100 kb. In the course of a fingerprint analysis of
      different Arabidopsis ecotypes we have detected four rDNA polymorphisms between
      the ecotypes Landsberg (La) and Niederzenz (Nd). Mapping of these polymorphisms
      using established segregating F2 populations reveals that all polymorphisms
      detected are dominant. Three of them map to the locus on the second chromosome
      that has been shown to harbour the NOR 2. The fourth polymorphism can be
      unambiguously assigned to the upper arm of the fourth chromosome. This is the
      first polymorphism found which originates in the second rDNA cluster of
      Arabidopsis thaliana. It enables localization of NOR 4 and thus completes the
      mapping of rDNA genes in the NORs of Arabidopsis.

PMID- 8569683
TI  - Overexpression of MerT, the mercuric ion transport protein of transposon Tn501,
      and genetic selection of mercury hypersensitivity mutations.
AB  - The small (116 amino acids) inner membrane protein MerT encoded by the transposon
      Tn501 has been overexpressed under the control of the bacteriophage T7 expression
      system. Random mutants of MerT were made and screened for loss of mercuric ion
      hypersensitivity. Several mutant merT genes were selected and sequenced: Cys24Arg
      and Cys25Tyr mutations abolish mercury resistance, as do charge-substitution
      mutations in the first predicted transmembrane helix (Gly14Arg, Gly15Arg,
      Gly27Arg, Ala18Asp), and the termination mutations Trp66Ter and Cys82Ter.

PMID- 8569684
TI  - Cloning and characterisation of genes (pkc1 and pkcA) encoding protein kinase C
      homologues from Trichoderma reesei and Aspergillus niger.
AB  - Oligonucleotides, designed on the basis of conserved flanking amino acid sequence
      segments within the catalytic domain of eukaryotic protein kinase C (PKC)
      proteins, were used as primers for polymerase chain reactions to amplify a 427-bp
      chromosomal DNA fragment from the filamentous fungus Trichoderma reesei. This
      fragment was then used to isolate genes encoding PKC homologues of T. reesei and
      Aspergillus niger (pkc1 and pkcA, respectively). The genes contain six (T.
      reesei) and eight (A. niger) introns, which exhibit notable conservation in
      position with those found in the corresponding Schizosaccharomyces pombe pkc1+
      and Drosophila melanogaster dPKC53Ebr genes. A single 4.2-kb transcript was
      detected in Northern analyses. The deduced PKC1 (T.reesei, 126 kDa) and PKCA (A.
      niger, 122 kDa) amino acid sequences reveal domains homologous to the C1 and
      C3/C4 domains of PKC-related proteins, but lack typical Ca(2+)-binding (C2)
      domains. Both contain a large, extended N-terminus, which shares a high degree of
      similarity with the corresponding regions of Saccharomyces cerevisiae PKC1 and S.
      pombe pkc1+ and pkc2+ proteins, but which is not present in PKCs of Dictyostelium
      or higher eukaryotes. This extended region can be divided into three subdomains;
      the N-terminal one contains a hydrophobic helix-turn-helix motif, whereas the C
      terminal one contains potential targets for proteolytic processing. A polyclonal
      antiserum raised against the pseudosubstrate-binding domain of PKC1 recognizes in
      T. reesei a 115-120 kDa protein in Western blots. Expression of pkc1 cDNA in
      insect cells directs the synthesis of a PKC1 protein of similar size. The T.
      reesei PKC1 protein was partially purified and some of its properties examined:
      it is stimulated about twofold by phospholipids or phorbol esters but is not
      stimulated by Ca2+. We conclude that these PKC proteins from filamentous fungi
      represent the Ca(2+)-insensitive fungal homologues of the nPKC family.

PMID- 8569685
TI  - Identification of elements in the PDA1 promoter of Nectria haematococca necessary
      for a high level of transcription in vitro.
AB  - Expression of the PDA1 gene in the ascomycete Nectria haematococca MPVI
      (anamorph: Fusarium solani) is induced by exposure of mycelium to pisatin, an
      isoflavonoid phytoalexin produced by its host plant, garden pea. The PDA1 gene
      encodes a cytochrome P-450 monooxygenase which detoxifies pisatin. Regulatory
      elements controlling transcription from the PDA1 promoter were identified using a
      homologous Nectria in vitro transcription system through analysis of 5'
      deletions, specific oligonucleotide competition, and fusion of upstream segments
      to a heterologous promoter. A promoter-distal element which provided
      transcriptional activation was localized to a 35-bp region positioned -514 to 
      483 upstream of the transcriptional start site. This 35-bp region binds a
      previously characterized pisatin-responsive DNA-binding factor (PRF) and thus may
      provide pisatin-responsive control of transcription. A second promoter-proximal
      positive-acting region was found to be necessary for promoter transcription in
      both homologous and heterologous extracts, and so is likely to bind less
      genespecific transcription activator(s). A negative-acting element located
      between these two positive regions may act to make the positive-acting elements
      interdependent. The identification of an activator responding to pisatin provides
      a model for the control of a number of genes and processes controlled by host
      specific signals, particularly the flavonoids.

PMID- 8569686
TI  - Characterization and genetic mapping of simple repeat sequences in the tomato
      genome.
AB  - Tomato genomic libraries were screened for the presence of simple sequence
      repeats (SSRs) with seventeen synthetic oligonucleotide probes, consisting of 2-
      to 5-basepair motifs repeated in tandem. GAn and GTn sequences were found to
      occur most frequently in the tomato genome (every 1.2 Mb), followed by ATTn and
      GCCn (every 1.4 Mb and 1.5 Mb, respectively). In contrast, only ATn and GAn
      microsatellites (n > 7) were found to be frequent in the GenBank database,
      suggesting that other motifs may be preferentially located away from genes.
      Polymorphism of microstellites was measured by PCR amplification of individual
      loci of by Southern hybridization, using a set of ten tomato cultivars.
      Surprisingly, only two of the nine microsatellite clones surveyed (five GTn,
      three GAn and one ATTn), showed length variation among these accessions.
      Polymorphism was also very limited between Lycopersicon esculentum and L.
      pennelli, two distant species. Southern analysis using the seventeen
      oligonucleotide probes identified GATAn and GAAAn as useful motifs for the
      detection of multiple polymorphic fragments among tomato cultivars. To determine
      the structure of microsatellite loci, a GAn probe was used for hybridization at
      low stringency on a small insert genomic library, and randomly selected clones
      were analyzed. GAn based motifs of increasing complexity were found, indicating
      that simple dinucleotide sequences may have evolved into larger tandem repeats
      such as minisatellites as a result of basepair substitution, replication
      slippage, and possibly unequal crossing-over. Finally, we genetically mapped loci
      corresponding to two amplified microsatellites, as well as nine large
      hypervariable fragments detected by Southern hybridization with a GATA8 probe.
      All loci are located around putative tomato centromeres. This may contribute to
      understanding of the structure of centromeric regions in tomato.

PMID- 8569687
TI  - Transcriptional regulation of the iron-responsive sigma factor gene pbrA.
AB  - In response to the intracellular iron concentration Pseudomonas fluorescens M114
      coordinately regulates the production of pseudobactin M114, its cognate receptor
      PbuA, and a casein protease. Transcriptional initiation of this coordinate iron
      stress response requires the sigma factor PbrA. PbrA is a member of the ECF
      (Extracytoplasmic function) subgroup of the sigma 70 family of eubacterial RNA
      polymerase sigma factors. Regulatory studies of the pbrA gene utilising promoter
      lacZ transcriptional fusions demonstrate that expression of pbrA dictates the
      cellular response to iron. pbrA is transcribed in all phases of iron-limited
      growth but maximally at late-logarithmic to stationary phase. pbrA expression is
      independent of autoregulatory control but is strictly repressed in iron-rich
      conditions in a Fur-dependent fashion. Constitutive expression of pbrA from an
      inducible tac promoter permits the induction of PbrA-dependent transcription and
      pseudobactin M114 biosynthesis in high-iron conditions. A PbrA consensus
      sequences was derived from significant DNA sequence homologies observed within
      the "-25 bp" and "-16 bp" regions conserved among all PbrA-dependent promoters.
      The predicted PbrA target promoter consensus is homologous for the promoter
      recognition sites for other environmentally responsive ECF sigma factors.

PMID- 8569689
TI  - AgTHR4, a new selection marker for transformation of the filamentous fungus
      Ashbya gossypii, maps in a four-gene cluster that is conserved between A.
      gossypii and Saccharomyces cerevisiae.
AB  - Single-read sequence analysis of the termini of eight randomly picked clones of
      Ashbya gossypii genomic DNA revealed seven sequences with homology to
      Saccharomyces cerevisiae genes (15% to 69% on the amino acid level). One of these
      sequences appeared to code for the carboxy-terminus of threonine synthase, the
      product of the S. cerevisiae THR4 gene (52.4% identity over 82 amino acids). We
      cloned and sequenced the complete putative AgTHR4 gene of A. gossypii. It
      comprises 512 codons, two less than the S. cerevisiae THR4 gene. Overall identity
      at the amino acid sequence level is 67.4%. A continuous stretch of 32 amino acids
      displaying complete identity between these two fungal threonine synthases
      presumably contains the pyridoxal phosphate attachment site. Disruption of the A.
      gossypii gene led to threonine auxotrophy, which could be complemented by
      transformation with replicating plasmids carrying the AgTHR4 gene and various S.
      cerevisiae ARS elements. Using these plasmids only very weak complementation of a
      S. cerevisiae thr4 mutation was observed. Investigation of sequences adjacent to
      the AgTHR4 gene identified three additional ORFs. Surprisingly, the order and
      orientation of these four ORFs is conserved in A. gossypii and S. cerevisiae.

PMID- 8569688
TI  - Caffeine-resistance in fission yeast is caused by mutations in a single essential
      gene, crm1+.
AB  - Caffeine is a base analogue and is known to affect a wide variety of cellular
      processes. In order to dissect genetically molecules which mediate the biological
      effects of caffeine, temperature-sensitive (ts) and caffeine-resistant mutants
      were isolated from fission yeast, Schizosaccharomyces pombe. Surprisingly, all
      twelve ts isolates contained a mutation in the same locus, crm1. Cells of the ts
      crm1 mutant showed an abnormal chromosome structure at the restrictive
      temperature, an elevated expression of Pap1-dependent transcription, and cross
      resistance to an unrelated drug such as staurosporine. Overproduction of pap1+
      also conferred caffeine resistance, whilst the resistance of the crm1 mutant is
      abolished in the pap1- background. These results show that the crm1+ gene is a
      major locus for caffeine resistance, which arises from Pap1-dependent
      transcriptional activation.

PMID- 8569690
TI  - A new family of DNA binding proteins includes putative transcriptional regulators
      of the Antirrhinum majus floral meristem identity gene SQUAMOSA.
AB  - Several sites of nuclear protein interaction within the promoter region of the
      Antirrhinum majus floral meristem identity gene SQUAMOSA were detected using an
      electrophoretic mobility shift assay. One of these sites displayed a particularly
      clear interaction with nuclear protein extracted from inflorescences but not with
      nuclear protein extracted from young, nonflowering plants. This site could thus
      represent a binding motif for a transcriptional activator. A South-western screen
      of an inflorescence cDNA expression library resulted in the isolation of several
      cDNAs representing two different genes named SBP1 and SBP2 (for SQUAMOSA-pROMOTER
      BINDING PROTEIN gene 1 and 2). Both genes encode highly similar protein domains
      which were found to be necessary and sufficient for binding DNA in a sequence
      specific manner. This DNA-binding domain showed no similarity to known proteins
      in the databases. However, it is characteristic for a small family of gene
      products in A. majus and other plant species. Expression of SBP1 and 2 is
      developmentally regulated and their transcriptional activation precedes that of
      SQUAMOSA. The data presented support the idea that members of the newly
      identified SBP gene family function as transcription factors involved in the
      control of early flower development.

PMID- 8569691
TI  - Escherichia coli cis- and trans-acting mutations that increase glyA gene
      expression.
AB  - We used an Escherichia coli strain blocked in serine biosynthesis and carrying a
      partial glyA deletion to isolate strains with altered regulation of the glyA
      gene. The glyA deletion results in 25% of the normal serine
      hydroxymethyltransferase activity. Three classes of mutants with increased glyA
      expression were isolated on glycine supplemented plates. One class of mutations
      increased glyA expression 10-fold by directly altering the -35 consensus sequence
      of the glyA promoter. The two other classes increased glyA expression about 2-
      and 6-fold, respectively. The latter two classes of mutations also affected
      regulation of the metE gene of the folate branch of the methionine pathway, but
      not metA in the nonfolate branch of the methionine pathway, or the gcv operon,
      encoding the glycine cleavage enzyme system. The mutations were mapped to about
      minute 85.5 on the E. coli chromosome.

PMID- 8569692
TI  - Indirect evidence of alteration in the expression of the rDNA genes in
      interspecific hybrids between Drosophila melanogaster and Drosophila simulans.
AB  - Crosses between Drosophila melanogaster females and D. simulans males produce
      viable hybrid females, while males are lethal. These males are rescued if they
      carry the D. simulans Lhr gene. This paper reports that females of the wild-type
      D. melanogaster population Staket do not produce viable hybrid males when crossed
      with D. simulans Lhr males, a phenomenon which we designate as the Staket
      phenotype. The agent responsible for this phenomenon was found to be the Staket X
      chromosome (Xmel, Stk). Analysis of the Staket phenotype showed that it is
      suppressed by extra copies of D. melanogaster rDNA genes and that the Xmel, Stk
      chromosome manifests a weak bobbed phenotype in D. melanogaster Xmel, Stk/0
      males. The numbers of functional rDNA genes in Xmel, Stk and Xmel, y w (control)
      chromosomes were found not to differ significantly. Thus a reduction in rDNA gene
      number cannot account for the weak bobbed Xmel, Stk phenotype let alone the
      Staket phenotype. The rRNA precursor molecules transcribed from the Xmel, Stk
      rDNA genes seem to be correctly processed in both intraspecific (melanogaster)
      and interspecific (melanogaster-simulans) conditions. It is therefore suggested
      that the Xmel, Stk rDNA genes are inefficiently transcribed in the melanogaster
      simulans hybrids.

PMID- 8569693
TI  - Cloning and characterization of the eapB and eapC genes of Cryphonectria
      parasitica encoding two new acid proteinases, and disruption of eapC.
AB  - Two new proteinases secreted by Cryphonectria parasitica, namely EapB and EapC,
      have been purified. The corresponding structural genes were isolated by screening
      a cosmid library, and sequenced. Comparison of genomic and cDNA sequences
      revealed that the eapB and eapC genes contain three and two introns,
      respectively. The products of the eapB and eapC genes as deduced from the
      nucleotide sequences, are 268 and 269 residues long, respectively. N-terminal
      amino acid sequencing data indicates that EapC is synthesized as a zymogen, which
      yields a mature 206-amino acid enzyme after cleavage of the prepro sequence.
      Similarly, sequence alignment studies suggest that EapB is secreted as a 203
      residue form which shares extensive similarities not only with EapC but also with
      two other acid fungal proteinases. However, they display distinct structural
      features; for example, no cysteine residue is found in EapC. The eapC gene was
      mutated using a two-step gene replacement strategy which allowed the specific
      introduction of several stop codons at the beginning of the eapC coding sequence
      in an endothiapepsin-deficient (EapA-) C. parasitica strain. Although the
      resulting strain did not secrete EapC, it still exhibited residual extracellular
      proteolytic activity, which could be due to EapB.

PMID- 8569694
TI  - Agonist responses of neuronal nicotinic acetylcholine receptors are potentiated
      by a novel class of allosterically acting ligands.
AB  - Similar to the gamma-aminobutyric acidA receptor and the N-methyl-D-aspartate
      subtype of glutamate receptor, neuronal nicotinic acetylcholine receptors are
      subject to positive modulatory control by allosterically acting ligands.
      Exogenous ligands such as galanthamine and the neurotransmitter 5
      hydroxytryptamine, when applied in submicromolar concentrations with nicotinic
      agonists, significantly increase the frequency of opening of nicotinic receptor
      channels and potentiate agonist-activated currents. Because these effects have
      been shown to be blocked by the monoclonal antibody FK1, they are mediated by
      binding sites that are located on alpha subunits of nicotinic receptors and
      distinct from those for acetylcholine and acetylcholine-competitive ligands. At
      higher concentrations, the potentiating effect of these ligands decreases and is
      eventually overcome by an inhibition of the agonist-induced response. The
      sensitizing actions of galanthamine, 5-hydroxytryptamine, and related compounds,
      at submicromolar concentrations, may reflect the existence of cross-talk between
      adjacent neuroreceptors and synapses in the central nervous system and thus
      suggests the formation of transiently active chemical networks in the vertebrate
      brain.

PMID- 8569695
TI  - Stereoselective and regioselective hydration of 7-methylbenz[c]acridine-5,6-oxide
      enantiomers by rodent and human microsomal epoxide hydrolases.
AB  - In the present study, we studied the regioselectivity and stereoselectivity of
      human microsomal epoxide hydrolase-catalyzed hydration of the enantiomers of the
      polycyclic aza-aromatic hydrocarbon K-region oxide, 7-methylbenz[c]acridine-5,6
      oxide. We used a human microsomal epoxide hydrolase cDNA amplified from a liver
      cDNA library and expressed in COS-7 cells. Comparisons were made with the
      activities of rat and HLM preparations. The determination of the apparent
      Michaelis-Menten kinetic constants revealed that microsomal epoxide hydrolase,
      regardless of the source, exhibited enantioselectivity, with the 5S,6R-oxide
      being the preferred substrate. Regioselectivity of hydration for each
      stereoisomer was determined. Expressed human microsomal epoxide hydrolase and HLM
      catalyzed the attack of water predominantly (approximately 96%) at C5 of the
      5R,6S-oxide, whereas 5S,6R-oxide was attacked less selectivity (approximately 60%
      at C5). These results are discussed in the context of available literature on the
      regioselectivity and stereoselectivity of rat and rabbit microsomal epoxide
      hydrolase and represents the first examination of human microsomal epoxide
      hydrolase regarding its regioselectivity and stereoselectivity of hydration.

PMID- 8569696
TI  - Constitutive activation of a single effector pathway: evidence for multiple
      activation states of a G protein-coupled receptor.
AB  - A cysteine-to-phenylalanine mutation in the third transmembrane domain of the
      alpha 1B-adrenergic receptor constitutively activates the receptor, resulting in
      G protein coupling in the absence of agonist and activation of only a single
      effector pathway (phospholipase C but not phospholipase A2). This mutant receptor
      displays a higher affinity for the catecholamines, norepinephrine, and
      epinephrine, as well as for other phenethylamines, but not for imidazolines, a
      class of structurally distinct alpha agonists. Dose-response studies demonstrate
      a higher potency and intrinsic activity of phenethylamines for
      polyphosphoinositide turnover but not for arachidonic acid release. Imidazolines
      have wild-type potencies and intrinsic activities for both pathways. These data
      indicate that a single receptor subtype forms multiple conformations (i.e.,
      exhibits induced conformational pleiotropy) for G protein interactions (high
      affinity states) that are specific for a particular G protein/effector pathway
      and that multiple binding sites exist for agonists, which promote or induce these
      specific interactions. Pharmacological diversity may, thus, be achieved through a
      single receptor by the development of compounds that induce a single activated
      conformer. This has major ramifications for the eventual development of signaling
      specific therapeutics.

PMID- 8569697
TI  - Effect of cyclothiazide on binding properties of AMPA-type glutamate receptors:
      lack of competition between cyclothiazide and GYKI 52466.
AB  - The effects of cyclothiazide on the properties of (R,S)-alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors were studied
      using equilibrium binding techniques and interactions with other compounds known
      to modulate the receptors. Cyclothiazide caused a reduction in [3H]AMPA binding
      in assays carried out in the presence of thiocyanate, a chaotropic ion that
      markedly increases the affinity of AMPA receptors and accelerates their
      desensitization. In the absence of thiocyanate, however, cyclothiazide had no
      reliable effect on the binding of [3H]AMPA or on the affinity for this agonist
      assessed from the displacement of [3H]CNQX. The interaction of cyclothiazide with
      the receptor appears not to be changed by the presence of thiocyanate. Analysis
      of the results with a kinetic model of the AMPA receptor suggests that
      cyclothiazide does not block receptor desensitization by making the desensitized
      state inaccessible but rather by stabilizing the active state, i.e., by
      increasing the affinity of the latter to a point where it becomes energetically
      more favorable than the desensitized state. GYKI 52466, an atypical
      benzodiazepine that blocks AMPA receptor-gated currents, did not reverse the
      changes in binding affinity produced by cyclothiazide in the presence of
      thiocyanate. Physiological experiments conducted in excised patches collected
      from hippocampal pyramidal cells indicated that thiocyanate does not block access
      of GYKI 52466 to AMPA receptors. These results point to the conclusion that
      cyclothiazide acts at a site on the AMPA receptor different from that for GYKI
      52466.

PMID- 8569698
TI  - Single amino acid substitutions in the pm2 muscarinic receptor alter receptor/G
      protein coupling without changing physiological responses.
AB  - The amino terminus of the third cytoplasmic loop of the porcine m2 muscarinic
      receptor plays an important role in receptor/effector coupling. Although large
      changes in coupling properties are easily detected, subtle changes are often
      overlooked. Three mutant receptors were characterized after expression in Chinese
      hamster ovary cells, and two of these exhibited subtle changes in coupling
      properties. Substitution of amino acids 219-223 (KDKKE) with those conserved in
      the m1/m3/m5 receptor subtype family (ELAAL) had little effect on coupling to
      effector systems, indicating that altering the charge distribution in this region
      did not affect receptor/G protein interactions. Substitution of alanine with
      glutamate at amino acid position 212 (A212E) or lysine with alanine in position
      214 (K214A) resulted in receptors with IC50 values for inhibition of adenylyl
      cyclase that resembled those of wild-type, although maximal percent inhibition
      was reduced. All mutants moderately decreased coupling to phosphatidylinositol
      metabolism, but mutant A212E caused oxotremorine-M to become a weak partial
      agonist compared with carbachol, suggesting that receptor conformation is agonist
      dependent even for ligands normally thought of as full agonists. K214A coupled to
      PI metabolism through both PTX-sensitive and PTX-insensitive G proteins. The
      results indicated that these mutants superficially possessed effector coupling
      characteristics similar to those of wild-type, but on more detailed examination G
      protein/receptor interactions were altered.

PMID- 8569699
TI  - Negative allosteric modulation of wild-type and mutant AMPA receptors by GYKI
      53655.
AB  - Benzothiadiazides such as cyclothiazide potentiate alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA) receptor responses, whereas 2,3-benzodiazepines
      such as 1-(4-aminophenyl)-3-methylcarbamyl-4-methyl-7,8-methylenedioxy-3,4 
      dihydro- 5H-2,3-benzodiazepine (GYKI 53655) act as noncompetitive antagonists;
      both drugs act through allosteric modulation. Controversy exists as to whether
      cyclothiazide and GYKI 53655 act at a common site. Recent mutational analysis has
      led to the identification of a serine residue in flip splice variants that is
      critical for directing the interaction of cyclothiazide with AMPA receptors. We
      tested whether the mutation of this residue to glutamine, which abolishes
      potentiation by cyclothiazide, can in addition block antagonism by 2,3
      benzodiazepines, as would be predicted for action at a common site. We found that
      the S to Q mutation does not alter antagonism by 2,3-benzodiazepines, suggesting
      that the molecular determinants directing the interaction between GYKI 53655 and
      AMPA receptors are not identical to those controlling sensitivity to
      cyclothiazide. Additional support for this was obtained from analysis of the
      responses of AMPA receptor flip/flop splice variants, which, despite differences
      in equilibrium desensitization and sensitivity to cyclothiazide, show only small
      differences in sensitivity to 2,3-benzodiazepines. Furthermore, introduction of
      the flip exon from GluRA into GluR6, conferred sensitivity to cyclothiazide but
      did not increase sensitivity to 2,3-benzodiazepines. Of interest, experiments
      with native AMPA receptors generated from hippocampal and forebrain poly(A)+ mRNA
      revealed greater sensitivity to 2,3-benzodiazepines than receptors generated by
      expression of recombinant AMPA receptors, possibly indicating the existence of an
      unidentified accessory protein or novel receptor subunit.

PMID- 8569700
TI  - Mitogenic effects of tetrahydrobiopterin in PC12 cells.
AB  - (6R)-5,6,7,8-Tetrahydrobiopterin (BH4), which is synthesized intracellularly from
      GTP, caused a concentration-dependent increase in rat pheochromocytoma (PC12)
      cell proliferation when added exogenously. Incubation with sepiapterin, which is
      converted enzymatically to BH4 within cells, also increased PC12 cell
      proliferation and BH4 levels concomitantly. These sepiapterin effects were
      mediated by BH4 as inhibition of sepiapterin conversion to BH4 by a sepiapterin
      reductase inhibitor, N-acetyl-serotonin, blocked the increase in proliferation
      and the elevation of BH4 levels. 7,8-Dihydrobiopterin (BH2) also increased BH4
      levels and PC12 cell proliferation, both of which were reversed by methotrexate,
      which blocks the conversion of BH2 to BH4 by dihydrofolate reductase. The BH4
      induced increase in PC12 cell proliferation was not related to elevated
      catecholamine or nitric oxide synthesis as inhibitors of tyrosine hydroxylase or
      nitric oxide synthase did not reduce the BH4 effect. BH4 and its precursors did
      not alter intracellular cAMP levels, suggesting that this second messenger is not
      involved in the enhancement of PC12 cell proliferation by BH4. Sepiapterin and
      BH4 also enhanced the proliferation of SV40-transformed human fibroblasts and rat
      C6 glioma cells, indicating that the stimulatory effect of BH4 on cell
      proliferation is not restricted to PC12 cells.

PMID- 8569701
TI  - Glucocorticoids inhibit the induction of nitric oxide synthase II by down
      regulating cytokine-induced activity of transcription factor nuclear factor-kappa
      B.
AB  - Incubation of human A549/8 cells with human interleukin-1 beta (50 units/ml),
      interferon-gamma (100 units/ml), and tumor necrosis factor-alpha (10 ng/ml)
      (cytomix) resulted in a marked expression of the mRNA of the inducible nitric
      oxide synthase (NOS II). This induction was prevented by cycloheximide.
      Dexamethasone markedly reduced cytokine-induced NOS II mRNA concentrations; this
      reduction was prevented by RU 38486 (mifepristone). Pyrrolidine dithiocarbamate,
      an inhibitor of nuclear factor-kappa B (NF-kappa B) activation, also
      significantly decreased cytomix-induced NOS II mRNA levels. When A549/8 cells
      were transfected with a construct containing 1570-bp 5'-flanking sequence of the
      murine NOS II gene cloned before a reporter gene, the murine NOS II promoter was
      induced up to 20-fold with cytomix but not with bacterial lipopolysaccharide.
      Dexamethasone as well as pyrrolidine dithiocarbamate inhibited this induction. In
      electrophoretic mobility shift assays, nuclear protein extracts from cytomix
      induced, but not from unstimulated cells, significantly slowed the migration of
      an oligonucleotide containing the NF-kappa B-binding site. This band shift was
      markedly reduced by dexamethasone. On the other hand, cytomix-induced nuclear
      protein content of NF-kappa B p65 and NF-kappa B p50 was not reduced by
      dexamethasone (as analyzed by Western blot). Dexamethasone also did not reduce
      cytomix-induced expression of NF-kappa B p65 mRNA or enhance the expression of NF
      kappa B inhibitor mRNA. The human and murine NOS II promoters also contain
      consensus sequences for activating protein-1 (AP-1) binding. However, AP-1
      binding activity of nuclear extracts of A549/8 cells was not enhanced by cytomix
      or inhibited by dexamethasone. These data suggest that the activated
      glucocorticoid receptor prevents (by a protein/protein interaction) the binding
      of transcription factor NF-kappa B, but not AP-1, to the NOS II promoter, thereby
      inhibiting the induction of NOS II transcription.

PMID- 8569702
TI  - Specific and effective interaction of a guanine nucleotide analogue with small G
      proteins.
AB  - G proteins are molecular switches that use a cycle of GTP binding and hydrolysis
      to regulate a wide variety of cellular biochemical processes. Because the
      functional state of these proteins is allosterically determined by bound guanine
      nucleotides, a nucleotide analogue with protein specificity might have
      pharmacological or biochemical value. The binding of [alpha-32P]GTP to four small
      G proteins immobilized on nitrocellulose was competed by a series of analogues
      with modifications at multiple sites. One analogue, N2-(p-n-butylphenyl)guanosine
      5'-(beta,gamma-difluoromethylene)triphosphate, had a approximately 40-fold higher
      affinity for one small G protein than for two of the others. Systematic analysis
      of each modification in the synthetic nucleotide revealed that specificity was
      conferred by the carbon substitution in the beta,gamma-phosphoanhydride bond.
      These observations were then extended to purified proteins of known sequence in
      solution by filtration binding studies with H-ras and rab5. Ras was 9-fold more
      discriminant between guanosine-5'-(beta,gamma-difluoromethylene)triphosphate and
      guanosine-5'-O-(3-thiotriphosphate) than was rab5, and the Q79L GTPase-defective
      mutant of rab5 was 6-fold more discriminant than wild-type rab5. Guanosine-5'
      (beta,gamma-difluoromethylene)triphosphate protected a 20-kDa fragment of rab5
      from tryptic proteolysis with greater efficacy than guanosine-5'-O-(3
      thiotriphosphate) or guanosine-5'-(beta,gamma-imido)triphosphate despite its
      lower affinity, and GMP stabilized a conformation indistinguishable from apo
      rab5. These results identify a synthetic guanine nucleotide analogue with
      differential affinity for closely related G proteins, determine the atomic
      substitution in the analogue that confers specificity, demonstrate discrimination
      by the analogue between wild-type and a point-mutant G protein, and establish
      efficacy of the analogue in inducing conformational change of a target protein
      disproportionate to the affinity of the interaction.

PMID- 8569703
TI  - Structure-activity relationship of quaternary ammonium ions at the external
      tetraethylammonium binding site of cloned potassium channels.
AB  - Changes in the chemical structure of the tetraethylammonium (TEA) ion reduce
      binding affinity at the external TEA receptor of outwardly rectifying potassium
      channels. To study the mechanism of selective binding, we applied a variety of
      hydrophilic quaternary ammonium (QA) ions to the noninactivating mutant of Shaker
      B T449Y, to Kv3.1, and to Kv3.1 mutants, expressed in Xenopus oocytes. In outside
      out patches, QA ions in which ethyl groups of TEA were replaced by methyl groups
      had a lower affinity than TEA, whereas changes in binding affinity were minor
      when propyl groups were substituted for ethyl groups. All channels tested showed
      this pattern. Changes in free energy of binding correlated well with changes in
      the computed free energy of hydration of the TEA derivatives that we used. The
      affinity for TEA derivatives was reduced in Kv3.1Y407T, which is in support of
      the hypothesis that cation pi-electron interaction is involved. Binding
      affinities of QA ions were higher in Kv3.1 Y407F than in the wild-type,
      suggesting that the hydroxyl groups of the tyrosines reduce QA binding. The rank
      order of potency of the QA ions toward the different channels studied was the
      same. These results indicate that external QA ions bind strongly to hydrophobic
      pi-electron-rich functions. The selectivity, however, is determined by the
      physical properties of the QA ion.

PMID- 8569704
TI  - Phenytoin-initiated hydroxyl radical formation: characterization by enhanced
      salicylate hydroxylation.
AB  - Bioactivation of phenytoin and related teratogens by peroxidases such as
      prostaglandin H synthase (PHS) may initiate hydroxyl radical (.OH) formation that
      is teratogenic. Salicylate is hydroxylated by .OH at the third and fifth carbon
      atoms, forming 2,3- and 2,5-dihydroxybenzoic acids (DHBA). In vivo salicylate
      metabolism produces only the 2,5-isomer, so 2,3-DHBA formation may reflect .OH
      production. In the present study, we validated the salicylate assay using the
      known .OH generator paraquat and evaluated .OH production by phenytoin. Female CD
      1 mice were treated with paraquat (30 mg/kg, intraperitoneally) given 30 min
      after acetylsalicylic acid (ASA) (200 mg/kg, intraperitoneally). Blood was
      collected at 5, 15, and 30 min and 1 and 2 hr after paraquat, and plasma was
      analyzed for DHBA isomers and glucuronide conjugates by high performance liquid
      chromatography with electrochemical detection. Paraquat increased 2,3-DHBA
      formation 19.2-fold, with substantial inter-individual variability in the time of
      maximal formation (p = 0.0001). The 2,3-DHBA glucuronide conjugates in vivo and
      in hepatic microsomal studies amounted to approximately 11% and 0.43%,
      respectively, of total 2,3-DHBA equivalents. To investigate putative .OH
      production initiated via PHS-catalyzed phenytoin bioactivation, ASA was given 30
      min before phenytoin (65 or 100 mg/kg, intraperitoneally), resulting in
      respective 7.6-fold (p = 0.02) and 14.2-fold (p = 0.003) increases in phenytoin
      initiated maximal 2,3-DHBA formation. Maximal 2,3-DHBA formation was 2.1-fold
      higher when ASA was administered after rather than before the same dose (65
      mg/kg) of phenytoin (p = 0.03), indicating ASA inhibition of PHS-catalyzed
      phenytoin bioactivation. Urinary analysis was much less sensitive, and the 2,5
      isomer reflected enzymatic rather than .OH-mediated hydroxylation. The paraquat
      studies demonstrate the importance of timing in accurately quantifying 2,3-DHBA
      formation and suggest that glucuronidation does not interfere. The substantial,
      dose-dependent initiation of 2,3-DHBA formation by phenytoin, and its inhibition
      by ASA, provide the first in vivo evidence that PHS-dependent .OH formation could
      contribute to the molecular mechanism of phenytoin teratogenesis.

PMID- 8569705
TI  - Stable activation and desensitization of beta 2-adrenergic receptor stimulation
      of adenylyl cyclase by salmeterol: evidence for quasi-irreversible binding to an
      exosite.
AB  - The relaxation of tracheal smooth muscle by the beta 2-adrenergic receptor (beta
      AR) agonist salmeterol displays several unusual properties: (i) slow onset of
      action (t1/2 = 5-15 min), (ii) prolonged activation (t1/2 = 8-14 hr), and (iii)
      the ability to recover from beta AR blockade. These properties led to the
      hypothesis that salmeterol binds with very high affinity to an exosite in
      addition to the beta AR activating site. Despite extensive characterization of
      salmeterol-induced bronchodilation, little is known about the molecular actions
      of salmeterol. We report the unique properties of salmeterol binding to the beta
      AR, activation of adenylyl cyclase, and desensitization of the hamster beta AR
      expressed in L cells. First, we found that salmeterol activation of adenylyl
      cyclase, although rapid and potent (low EC50 relative to epinephrine), was
      nevertheless remarkably inefficient relative to the full agonist epinephrine.
      Reduced coupling efficiency of salmeterol was demonstrated using formulations
      recently introduced by our group. Second, we found that pretreatment of L cells
      with salmeterol led to a stable activation of adenylyl cyclase that survives
      extensive wash procedures and sucrose step gradient purification of plasma
      membrane fractions. This activation of basal adenylyl cyclase did not require
      salmeterol binding to the classic active site during pretreatment, as it occurred
      in the presence of an excess of a beta AR antagonist. Third, we found that the
      rapid phase of salmeterol-induced desensitization was much reduced relative to
      epinephrine, consistent with its poor coupling efficiency and with its prolonged
      activation of adenylyl cyclase. These unique properties of salmeterol support the
      proposal that it binds reversibly to the activating or active site and as well to
      an extremely high affinity exosite from which it has access to the active site.

PMID- 8569706
TI  - Thrombin receptor activation by thrombin and receptor-derived peptides in
      platelet and CHRF-288 cell membranes: receptor-stimulated GTPase and evaluation
      of agonists and partial agonists.
AB  - Thrombin receptor activation, by thrombin or SFLLR-containing peptides,
      stimulates GTPase activity in platelet and CHRF-288 membranes. Polyclonal
      antibodies to peptides derived from the thrombin receptor (anti-TR52-69 and anti
      TR36-49), which block many of thrombin's actions on platelets and endothelial
      cells, also block thrombin activation of membrane GTPase (as does thrombin active
      site and anion-binding exosite inhibitors). Most of the receptor-activated
      GTPase, stimulated by both thrombin and SFLLRNP in platelet membranes, was
      inhibited by prior treatment with pertussis toxin or N-ethylmaleimide, suggesting
      that under these conditions much of the thrombin receptor-stimulated GTPase in
      platelet membranes is a member of the pertussis toxin-sensitive G alpha i family.
      In platelet membrane preparations, the peptide agonists stimulated approximately
      twice as much GTPase activity as stimulated by alpha-thrombin. In contrast, the
      membranes prepared from CHRF-288 cells showed similar maximal SFLLRNP- and alpha
      thrombin-stimulated GTPase activity. Stimulation of the platelet membrane GTPase
      by a variety of different peptide agonists correlated with their ability to
      stimulate platelet aggregation. Several peptide-based agonists were more potent
      than the wild-type sequence. The most potent was Ser-(p-fluoro-Phe)-(2-Napthyl
      Ala)-Leu-Arg-NH2, which stimulated platelet aggregation (EC50 = 80 nM) and GTPase
      activity (EC50 = 110 nM). The peptide YFLLRN stimulated GTPase activity but only
      to approximately 40% of the activity observed with optimal concentrations of
      other receptor agonists. YFLLRN also limited the stimulation observed with
      SFLLRNP in a competitive fashion, indicating that YFLLRN is a competitive partial
      agonist at the thrombin receptor. These studies show that the tethered-ligand
      receptor mediates the GTPase activation by thrombin in platelet and CHRF-288 cell
      membranes, and this provides a specific, reliable, and convenient cell-free assay
      system with which one can evaluate agonists and partial agonists.

PMID- 8569707
TI  - The binding of propranolol at 5-hydroxytryptamine1D beta T355N mutant receptors
      may involve formation of two hydrogen bonds to asparagine.
AB  - Although the beta-adrenergic receptor antagonist (-)-propranolol binds with
      relatively low affinity at human 5-hydroxytryptamine1D beta receptors (Ki =
      10,200 nM), it displays significantly higher affinity (Ki = 17 nM) at its species
      homolog, 5-HT1B receptors, and at a mutant 5-HT1D beta receptor (Ki = 16 nM),
      where the threonine residue at position 355 (T355) is replaced with an asparagine
      residue (i.e., a T355N mutant). Propranolol contains two oxygen atoms, an ether
      oxygen atom and a hydroxyl oxygen atom, and it has been speculated that the
      enhanced affinity of propranolol for the T355N mutant receptor is related to the
      ability of the asparagine residue to hydrogen bond with the ether oxygen atom.
      However, the specific involvement of the propranolol oxygen atoms in binding to
      the wild-type and T355N mutant 5-HT1D beta receptors has never been addressed
      experimentally. A modification of a previously described 5-HT1D beta receptor
      graphic model was mutated by replacement of T355 with asparagine. Propranolol was
      docked with the wild-type and T355N mutant 5-HT1D beta receptor models in an
      attempt to understand the difference in affinity of the ligand for the receptors.
      The binding models suggest that the asparagine residue of the mutant receptor can
      form hydrogen bonds with both oxygen atoms of propranolol, whereas the threonine
      moiety of the wild-type receptor can hydrogen-bond only to one oxygen atom. To
      test this hypothesis, we prepared and examined several analogues of propranolol
      that lacked either one or both oxygen atoms. The results of radioligand binding
      experiments are consistent with the hypothesis that both oxygen atoms of
      propranolol could participate in binding to the mutant receptor, whereas only the
      ether oxygen atom participates in binding to the wild-type receptor. As such,
      this is the first investigation of serotonin receptors that combines the use of
      molecular modeling, mutant receptors generated by site-directed mutagenesis, and
      synthesis to investigate structure/affinity relationships.

PMID- 8569708
TI  - Characterization of the G protein involved in the muscarinic stimulation of
      adenylyl cyclase of rat olfactory bulb.
AB  - We investigated the identity of the G protein mediating the muscarinic
      stimulation of adenylyl cyclase in rat olfactory bulb membranes by examining the
      sensitivity of this response to selective anti-G protein antisera. Preincubation
      of tissue membranes with the antisera AS/7 (anti-Gi1/2 alpha), EC/2 (anti-Gi3
      alpha/Go alpha), and GO/1 (anti-G(o) alpha) but not with the antiserum QL (anti
      Gq/11 alpha) significantly attenuated the carbachol-stimulated adenylyl cyclase
      activity. These antisera had no effect on the enzyme activity stimulated by the
      beta-adrenergic agonist L-isoproterenol. On the other hand, the anti-Gs alpha
      antiserum RM/1 markedly depressed both carbachol- and L-isoproterenol-stimulated
      adenylyl cyclase activities. This antiserum also reduced the basal enzyme
      activity to a similar extent. However, different than the anti-Gi/Go antisera,
      the RM/1 antiserum failed to affect the carbachol-stimulated [35S]guanosine 5'-O
      (3-thiotriphosphate) binding to membrane G proteins, whereas it curtailed the
      [35S]guanosine 5'-O-(3-thiotriphosphate) binding stimulated by pituitary
      adenylate cyclase-activating peptide. Exposure to either pertussis toxin or the
      anti-Go alpha antiserum 9072 but not to cholera toxin or the anti-Gs alpha
      antiserum 1191 reduced the high-affinity binding of oxotremorine M to muscarinic
      receptors. Moreover, the labeling of a 45-kDa protein catalyzed by cholera toxin
      was markedly stimulated by pituitary adenylate cyclase-activating peptide but not
      by carbachol. These data indicate that in rat olfactory bulb membranes,
      muscarinic receptors interact with both Gi and Go and that these G proteins
      mediate the stimulation of adenylyl cyclase. Although this response appears to
      require Gs activity, no evidence was found for the direct coupling of muscarinic
      receptors to Gs.

PMID- 8569709
TI  - Coexpression of beta 1 with cardiac sodium channel alpha subunits in oocytes
      decreases lidocaine block.
AB  - Coexpression of the rat beta 1 subunit with rat brain and skeletal muscle sodium
      channel alpha subunits in Xenopus oocytes normalizes currents by accelerating
      sodium current decay kinetics, shifting steady state availability relationships,
      and accelerating recovery from inactivation. Unlike brain and skeletal muscle,
      the heart alpha subunit expressed without beta 1 has native-like decay kinetics
      in oocytes. Messenger RNA for beta 1 has been found in heart, but whether and how
      it affects cardiac sodium channel function are unclear. We studied coexpression
      of human heart alpha subunit with beta 1 in Xenopus oocytes using two
      microelectrode voltage-clamp and macropatch techniques. Coexpression with beta 1
      caused a significant positive shift of 3-7 mV in the midpoint of the steady state
      inactivation relationship but did not affect single-channel conductance,
      activation, current decay, or recovery from inactivation. Sensitivity to
      lidocaine block, however, was decreased for both resting state block (Kd = 0.5
      1.3 mM) and phasic block in response to pulse trains, but inactivated state block
      was not affected (Kd = approximately 10 microM). Coexpression with beta 1
      increased the rate of recovery from lidocaine block, which accounted for the
      major part of the observed differences in tonic and phasic block. A beta 1
      construct with the cytoplasmic tail removed also produced these effects,
      demonstrating that the beta 1 cytoplasmic tail was not involved in altering
      lidocaine block. We conclude that the beta 1 subunit is capable of affecting
      function of the cardiac sodium channel in oocytes by decreasing tonic and phasic
      lidocaine block with small effects on gating.

PMID- 8569710
TI  - Ethanol increases the activity of large conductance, Ca(2+)-activated K+ channels
      in isolated neurohypophysial terminals.
AB  - Large conductance, Ca(2+)-activated K+ channels are believed to underlie
      interburst intervals and, thus, contribute to the control of hormone release from
      neurohypophysial terminals. Because ethanol inhibits the release of vasopressin
      and oxytocin, we studied its effects on large conductance, Ca(2+)-activated K+
      channels from these terminals using patch-clamp techniques. Ethanol (10-100 mM)
      applied to the cytosolic surface of excised, inside-out patches reversibly
      increases channel activity in a concentration-dependent manner, reaching a
      plateau at 50-100 mM. This activation is not mediated by freely diffusible
      cytosolic second messengers or the release of Ca2+ from intracellular stores.
      Rather, it likely reflects a direct interaction of ethanol with the channel
      protein or a closely associated component. Neither the unitary conductance nor
      the characteristics of the voltage-current relationship are modified by the drug.
      The increase of channel activity by ethanol results from a modification of
      channel gating properties: the contribution of long openings to the total time
      spent in the open state is increased, the average duration of the fast openings
      is slightly increased, and long closures disappear in the presence of the drug.
      The activation of large conductance, Ca(2+)-activated K+ channels by ethanol, in
      conjunction with the previously reported inhibition of voltage-dependent Ca2+
      channels, can explain the reduced release of vasopressin and oxytocin after
      ethanol ingestion.

PMID- 8569711
TI  - Palytoxin-induced Na+ influx into yeast cells expressing the mammalian sodium
      pump is due to the formation of a channel within the enzyme.
AB  - Palytoxin forms ionic channels in animal cell membranes but does not have similar
      effects on bacteria or yeast cells. These channels appear to be associated with
      the sodium pump. Using a heterologous expression system for the mammalian sodium
      pump in the yeast Saccharomyces cerevisiae, we recently demonstrated palytoxin
      induced K+ efflux from yeast cells. Using the same system, we now show that the
      palytoxin-induced Na+ influx measured by others in animal cells is also directly
      associated with the sodium pump. Under the influence of palytoxin, yeast cells
      that express the mammalian sodium pump exchange extracellular Na+ ions for
      intracellular K+ ions with a stoichiometry of approximately 1:1. Both fluxes can
      be inhibited by ouabain. K+ efflux can also be observed when extracellular Na+ is
      replaced by Li+, Cs+, or NH4+. These data suggest that all palytoxin-induced ion
      fluxes measured so far in various cell systems are directly associated with the
      sodium pump. Palytoxin-induced Na+ influx or K+ efflux does not occur with yeast
      cells that express a truncated form of the sodium pump that is missing 44 of the
      carboxyl-terminal amino acids of the alpha 1 subunit. Scatchard analysis reveals
      only a slightly lower affinity of the truncated form for [3H]ouabain compared
      with the affinity of the native enzyme. Yeast cells expressing the truncated
      enzyme can bind [3H]ouabain, which can be displaced by palytoxin. Therefore, the
      inability of the truncated form to conduct ions under the influence of palytoxin
      is not due to the removal of the palytoxin binding site but rather to the removal
      of a part of the enzyme that participates in a direct or indirect way in the
      formation of the palytoxin-induced channel. Based on these findings, we conclude
      that palytoxin opens a channel within and not merely in the vicinity of the
      sodium pump. This might be the same channel that under normal conditions actively
      transports Na+ and K+ ions.

PMID- 8569712
TI  - Inhibition of human interferon-gamma biosynthesis by an antisense RNA-expressing
      vector.
AB  - We applied antisense RNA technology for reducing the level of human IFN-gamma
      (HuIFN-gamma) expression. An antisense RNA vector containing the full-length
      HuIFN-gamma cDNA in the opposite orientation was electroporated into cells
      constitutively producing very high levels of the cytokine. Approximately 53% of
      the resulting clones exhibited a specific HuIFN-gamma inhibition of an average of
      95.5%. The results of reverse transcription-polymerase chain reaction and
      Northern blot analyses revealed that the antisense effect originated from a
      specific reduction of the targeted mRNA caused by antisense RNA expression. This
      very effective antisense RNA strategy can have possible therapeutic applications
      in treating diseases where HuIFN-gamma is known to play a negative role, such as
      in certain autoimmune diseases.

PMID- 8569713
TI  - Identification of a novel dexamethasone responsive enhancer in the human CYP3A5
      gene and its activation in human and rat liver cells.
AB  - The human liver cytochromes P450 3A (CYP3As), orthologous to the rat
      glucocorticoid inducible forms, are composed of at least four differentially
      expressed members. To begin the study of the molecular events in the
      glucocorticoid regulation of CYP3A5, we fused 5' sequences of CYP3A5 to the
      chloramphenicol acetyltransferase gene in a vector that contains the herpes
      simplex virus thymidine kinase promoter. In HepG2 cells, the largest 5' CYP3A5
      gene fragment (1.4 kb) suppressed the TK promoter. However, suppression was
      overcome by addition of 10 microM dexamethasone. A series of unidirectional
      deletions revealed a unique 219-bp fragment (-891 to -1109 bp upstream from the
      transcriptional start site) that conferred dexamethasone responsiveness on the TK
      promoter regardless of either the distance or orientation from the promoter and
      thus appears to be an enhancer. Nucleotide sequence analysis of this CYP3A5
      enhancer revealed no consensus 15-bp glucocorticoid responsive element (GRE)
      (GGTACANNNTGTTCT); however, two GRE "half-sites" (TGTTCT) were found separated by
      160 bp. Although dexamethasone stimulated the CYP3A5 enhancer only 3-4-fold in
      HepG2 cells, the CYP3A5 enhancer was stimulated 7- and 12-fold in immortalized
      primary human hepatocytes and primary rat hepatocyte cultures, respectively. The
      glucocorticoid receptor (GCR) seems to be indispensable to this process because
      1) dexamethasone induction can be blocked by the antiglucocorticoid RU-486, 2)
      dexamethasone-dependent transcriptional activation of the CYP3A5 enhancer in
      HepG2 cells required cotransfection of an expression vector containing the intact
      GCR, yet 3) cotransfection with a plasmid that contains a mutation in the ligand
      binding domain of the GCR does not activate the CYP3A5 enhancer in the presence
      of dexamethasone. To further localize the dexamethasone responsive region of the
      219-bp CYP3A5 enhancer, it was subdivided and fused to the TKCAT expression
      vector. Transfection analysis in HepG2 cells demonstrated that neither GRE half
      site can independently confer dexamethasone responsiveness on the TK promoter.
      Block mutations of either of the two GRE half-sites or point mutations at
      specific GCR binding sites eliminates dexamethasone inducibility, demonstrating
      the half-sites need to interact. Electromobility shift assays indicate that the
      CYP3A5 5'-GRE half-site 1) specifically binds purified GCR, 2) can displace
      binding of the GCR to a consensus GRE, and 3) shifts a protein in HepG2 nuclear
      extracts that is supershifted by GCR antibody, demonstrating that this enhancer
      is an authentic GRE. This is the first study to demonstrate that a member of the
      human CYP3A gene family contains an enhancer that binds the GCR and that this
      binding is critical to transcriptional activation by dexamethasone.

PMID- 8569714
TI  - Functional studies of the first selective beta 3-adrenergic receptor antagonist
      SR 59230A in rat brown adipocytes.
AB  - The SS-enantiomer 3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahy dronaphth-1
      ylaminol]-(2S)-2-propanol oxalate (SR 59230A) is proposed to be the first beta 3
      adrenergic receptor antagonist. The present work shows that SR 59230A, unlike its
      inactive RR-enantiomer (SR 59483), antagonized a typical beta 3-adrenergic
      response in vitro, i.e., SR 58611A, the ethyl-[(7s)-7-[[(2R)-2-(3- chlorophenyl)
      2-hydroxethyl]amino]-5,6,7,8-tetrahydronaphth- 2- yl]oxyacetate hydrochloride- or
      (-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one (CGP 12177)-stimulated
      synthesis of cAMP in rat brown adipose tissue membranes, with pKB values of 8.87
      +/- 0.12 and 8.20 +/- 0.15. In addition, SR 59230A had no antagonistic effect on
      forskolin-induced cAMP accumulation in rat interscapular brown adipose tissue. SR
      59230A, in contrast to the selective beta 1- and beta 2-adrenoceptor antagonists
      (+/-)[2-(3-carbamoyl-4-hydroxyphenoxy)-ethylamino]- 3-[4(1-methyl-4
      trifluoromethyl-2-imidazolyl)-phenoxy]-2 propanol and erythro-(+/-)-1-(7
      methylindan-4-yloxy)-3-isopropylaminob utan- 2-ol-hydrochloride did not
      counteract the cAMP production induced by (-)-isoprenaline or norepinephrine (NE)
      in rat brain areas rich in beta 1- or beta 2-adrenoceptors, such as frontal
      cortex and cerebellum. Moreover, in proliferating brown fat cells, in which the
      beta 1-adrenoceptor is the only beta-adrenergic subtype coupled to cAMP
      production, SR 59230A did not modify the production of cAMP induced by NE,
      whereas CGP 12177 did. In confluent brown fat cells, in which the beta 3
      adrenoceptor is the functional beta-adrenergic subtype coupled to adenylyl
      cyclase, SR 59230A antagonized the NE-induced cAMP accumulation and glycerol
      release without affecting their basal values, whereas CGP 12177, which per se
      stimulated cAMP accumulation and glycerol release, did not change the NE-induced
      increase of either parameter. Finally, SR 59230A concentration-dependently
      counteracted the NE-stimulated synthesis of uncoupling protein gene in confluent
      brown fat cells, which is considered mainly a result of selective stimulation of
      beta 3-adrenoceptors. These results provide evidence that the new selective beta
      3-adrenoceptor antagonist can contribute considerably to functional
      characterization of the beta 3-adrenoceptors.

PMID- 8569715
TI  - Thiophosphorylation of the G protein beta subunit in human platelet membranes:
      evidence against a direct phosphate transfer reaction to G alpha subunits.
AB  - A direct phosphate transfer reaction from the G protein beta subunits to either
      Gs alpha or Gi alpha has been proposed to account for the ability of
      thiophosphorylated transducin beta gamma-dimers to bidirectionally regulate
      adenylyl cyclase activity in human platelet membranes. We searched for
      experimental evidence for this reaction. Incubation of human platelet membranes
      with [35S]guanosine-5'-(3-O-thio)triphosphate ([35S]GTP gamma S) results in the
      predominant incorporation of [35S]thiophosphate into a 36-kDa protein, which
      comigrates with the G protein beta subunit and is immunoprecipitated by a beta
      subunit-specific antiserum. Thiophosphorylation of the beta subunit is specific
      for guanine nucleotides and abolished by the histidine-modifying agent
      diethylpyrocarbonate and heat and acid treatment. Dephosphorylation of
      [35S]thiophosphorylated beta subunits is accelerated in the presence of GDP, but
      not ADP, UDP, or guanosine-5'-(2-O-thio)diphosphate. Neither the
      thiophosphorylation nor the dephosphorylation is sensitive to receptor agonists
      (alpha 2-adrenergic, A2 adenosine, thrombin, or insulin), and purified G protein
      alpha subunits do not act as thiophosphate donors. An approach was designed to
      demonstrate direct thiophosphate transfer to protein-bound nucleotides; platelet
      membranes were sequentially exposed to NaIO4, NaCNBH3, and NaBH4, an oxidation
      reduction step that covalently incorporates prebound nucleotides into proteins.
      Under these conditions, multiple radiolabeled proteins are visualized on
      subsequent addition of [35S]GTP gamma S. This reaction is specific because both
      oxidation and reduction are required and pretreatment of platelet membranes with
      2',3'-dialdehyde GTP gamma S or diethylpyrocarbonate blocks the subsequent
      labeling in oxidized and reduced membranes. The G protein beta subunit may
      participate in this thiophosphate transfer reaction. Most important, however, no
      labeled G protein alpha subunits (Gs alpha and Gi alpha) were recovered by
      immunoprecipitation from oxidized and reduced membranes subsequent to the
      addition of [35S]GTP gamma S. Thus, our results clearly rule out the existence of
      a postulated G protein activation by phosphate transfer reactions, which lead to
      the formation of GTP from GDP prebound to the alpha subunit.

PMID- 8569716
TI  - Protein kinase C isozyme-specific modulation of cyclic AMP-dependent
      phosphodiesterase in hypertrophic cardiomyopathic hamster hearts.
AB  - We recently demonstrated that protein kinase C (PKC) activities were elevated in
      hypertrophic cardiomyopathic (HCM) hamster hearts and that activation of PKC
      resulted in stimulation of cAMP-dependent phosphodiesterase (PDE) activity. In
      this study, we determined the composition of PKC isozymes in control and HCM
      hearts and identified the PKC isozyme responsible for the modulation of PDE
      activity in HCM hearts. Using quantitative autoradiographic techniques with PKC
      isozyme-specific antibodies, we found that the PKC alpha, epsilon, and zeta
      isozymes were expressed in both control and HCM hearts. The immunoreactive
      amounts of cytosolic PKC alpha and PKC epsilon and of membrane PKC zeta were
      significantly increased in HCM hearts. The enzymatic activity of PKC in HCM
      hearts was significantly elevated in both membrane (148.0 +/- 13.7 versus 78.9 +/
      1.9 pmol/mg/min in controls, four experiments) and cytosol (117.3 +/- 5.1 versus
      75.7 +/- 5.1 pmol/mg/min in controls, four experiments). Contribution of
      individual PKC isozyme activity was assessed by the immunoprecipitable PKC
      activity with isozyme-specific antibodies. The membrane PKC epsilon (41.7 +/- 4.9
      versus 18.7 +/- 0.3 pmol/mg/min in controls, four experiments, p < 0.05) and PKC
      zeta (61.5 +/- 14.0 versus 20.3 +/- 2.7 pmol/mg/min in controls, four
      experiments, p < 0.05) but not PKC alpha (50.9 +/- 6.8 versus 44.3 +/- 1.5
      pmol/mg/min, four experiments, p = N.S.) were increased in HCM hearts. On the
      other hand, the cytosolic PKC alpha (47.7 +/- 4.1 versus 27.0 +/- 1.4
      pmol/mg/min, four experiments, p < 0.05) and PKC epsilon (42.8 +/- 3.1 versus
      19.1 +/- 3.9 pmol/mg/min, four experiments, p < 0.05) but not PKC zeta (27.2 +/-
      3.0 versus 32.0 +/- 2.1, four experiments, p = N.S.) were increased in HCM
      hearts. Furthermore, after immunoprecipitation of PKC alpha, activation of PKC
      could no longer potentiate the PDE activity in HCM hearts. Removal of PKC epsilon
      or PKC zeta, on the other hand, did not affect the PKC-mediated PDE stimulation
      in HCM hearts. These results suggest that there is an increase in the
      quantitative expression of PKC isozymes in HCM hearts and that the cross-talk
      between PKC and PDE in these hearts is mediated specifically via the PKC alpha
      isozyme.

PMID- 8569717
TI  - The tyrosine within the NPXnY motif of the human angiotensin II type 1 receptor
      is involved in mediating signal transduction but is not essential for
      internalization.
AB  - The NPXnY motif is involved in the internalization process of several types of
      receptors, including lipoprotein receptors and G protein-coupled receptors. We
      replaced Tyr302 with either phenylalanine or alanine in the NPLFY site of the
      human angiotensin II receptor type 1 and determined the pharmacological
      properties of the resulting mutant receptors. Competitive binding experiments
      revealed that COS-7 cells transfected with either the wild-type or mutant
      receptors expressed approximately the same amount of high affinity binding sites
      (Bmax 70,000 sites/cell and Kd approximately 2 nM). Photoaffinity labeling of
      both native and mutant receptors revealed apparent molecular masses of 110 kDa.
      Incubation of transfected cells with 0.2 nM [125I]Ang II at 37 degrees revealed
      an efficient internalization of the wild-type receptor and the mutant receptors,
      although the mutant receptors were internalized at a slower rate. Interestingly,
      however, the transmembrane signaling was severely impaired in transfected cells
      expressing mutant receptors. No significant production of inositol-1,4,5
      trisphosphate was observed when these cells were challenged for 3 min with a
      concentration of angiotensin II as high as 1 microM. This is in contrast to the
      dose-dependent stimulation of inositol-1,4,5-trisphosphate production in cells
      expressing the wild-type receptor. Thus, our results show that the Tyr302 in the
      NPXnY motif of the human angiotensin II receptor type 1 is not essential for
      agonist binding properties or for internalization of the receptor but plays an
      important role in transmembrane signaling.

PMID- 8569718
TI  - Prolonged exposure to agonist results in a reduction in the levels of the Gq/G11
      alpha subunits in cultured vascular smooth muscle cells.
AB  - Recent studies have shown that G proteins are a potential regulatory site in the
      transmembrane signaling cascade. The aim of this study was to examine the effects
      of prolonged agonist exposure on expression of the Gq class of G protein alpha
      subunits (G alpha q/G alpha 11) in cultured rat vascular smooth muscle cells
      (VSMC). Treatment with 100 nM angiotensin II (Ang II) led to a substantial
      sustained down-regulation of cellular levels of immunologically detectable G
      alpha q/G alpha 11 by 50% within 6 hr. The effect of Ang II was dose dependent
      with an EC50 of 2 nM and was specifically blocked by the vascular type-1 Ang II
      receptor-specific antagonist losartan. The Ang II-induced reduction in cellular
      levels of G protein alpha subunits was specific for G alpha q/G alpha 11. The
      calcium ionophore ionomycin or activators of ubiquitous protein kinases (phorbol
      12-myristate-13-acetate, forskolin, and 8-bromo-cGMP) did not mimic the effects
      of Ang II. However, [Arg8]vasopressin also induced a significant loss in cellular
      G alpha q/G alpha 11 levels. Ang II-induced G alpha q/G alpha 11 down-regulation
      was reversed by prevention of cellular receptor processing with phenylarsine
      oxide or chronic potassium depletion. The effects of Ang II on G alpha q/G alpha
      11 levels were inhibited when protein kinase C activity was abolished. G alpha q
      mRNA levels were down-regulated by 30% after 4-hr incubation with Ang II, in part
      by transcriptional regulation. Although a short term vasopressin pretreatment had
      no effect on inositol-1,4,5-trisphosphate (IP3) generation in response to
      subsequent Ang II stimulation, a partial heterologous desensitization of the IP3
      response was induced after a long term vasopressin pretreatment, which
      concurrently down-regulated cellular G alpha q/G alpha 11 levels. Homologous
      desensitization of IP3 generation on a second Ang II stimulation was observed
      after both a short and long term Ang II pretreatment. In conclusion, prolonged
      exposure to Ang II induces down-regulation of cellular G alpha q/G alpha 11
      levels in intact VSMC. The effect of Ang II appears to be mediated by the
      signaling pathway sensitive to inhibition of receptor processing. The present
      study raises the possibility that agonist-induced G alpha q/G alpha 11 down
      regulation participates in the mechanism of long term desensitization of the G
      alpha q/G alpha 11-mediated signaling system in VSMC.

PMID- 8569719
TI  - Second Messenger Systems--Molecular, Cellular and Behavioural Aspects.
      Proceedings of an international symposium. Tobago, June 16-17,1994.

PMID- 8569721
TI  - Preliminary crystallization studies of calmodulin-dependent protein phosphatase
      (calcineurin) from bovine brain.
AB  - Calcineurin is a serine/threonine protein phosphatase which catalyzes the
      hydrolysis of both phosphoseryl/phosphothreonyl and phosphotyrosyl proteins as
      well as low molecular weight compounds such as p-nitrophenyl phosphate. It is a
      hetero-dimeric protein consisting of a 60 kDa A chain and 19 kDa B chain.
      Calcineurin A is organized into functionally distinct domains such as a catalytic
      domain, a calcineurin B binding domain, a calmodulin-binding domain, and an
      inhibitory domain. Calcineurin B has four EF-hand calcium binding domains with a
      secondary structure that is homologous to calmodulin but its metal binding
      properties are more similar to troponin-C. The N-terminal myristoyl group of
      calcineurin B might play a role in the interaction between subunits A and B
      during phosphorylation/dephosphorylation processes. Crystals of size 0.125 x 0.07
      x 0.03 mm and 0.7 x 0.03 x 0.02 mm have been obtained for calcineurin and the A
      subunit respectively. Crystals of calcineurin show strong diffraction to 5.3 A
      and weak diffraction to 3.0 A on rotating anode operated at 50 kV and 100 mA.
      Further work is in progress to improve the X-ray diffraction quality of these
      crystals and to obtain well diffracting crystals of calcineurin B.

PMID- 8569722
TI  - Starvation reduces pyruvate dehydrogenase phosphate phosphatase activity in rat
      kidney.
AB  - Pyruvate dehydrogenase complex (PDC) from rat kidney or pig heart previously
      inactivated by phosphorylation (PDHP) was activated in vitro by PDHP phosphatase
      from kidneys of starved or fed rats. Starvation for 48 h of the rats from which
      the PDC was prepared led to a decrease in the rate of activation of PDC at early
      time periods (< 2 min), particularly at submaximal concentrations of Mg2+. Using
      intact permeable kidney mitochondria incubated for 15 sec, it was found that
      starvation of rats more than doubled the Mg2+ concentration at which the half
      maximal increment of PDC activity (PDCa) was observed. Reduction of PDHP
      phosphatase activity due to starvation was also apparent when phosphatase was
      separated from PDC and recombined with PDC from the same or different animals.
      Intraperitoneal injection of insulin and glucose 1 h before sacrifice of starved
      rats prevented the reduction of PDHP phosphatase activity whether or not protein
      synthesis was inhibited. The effect of insulin in restoration of PDHP phosphatase
      activity of starved rats was not mimicked by 5-methylpyrazole 3-carboxylic acid,
      an inhibitor of lipolysis. When renal PDHP phosphatase was incubated with pig
      heart PDC in the presence of 10 mM Mg2+ and 0.1 mM Ca2+ the increment in PDCa, in
      1 min was 30% of fully activated PDC activity (PDCt) observed after 15 min.
      Removal of divalent cations did not affect the increment in 1 min but prevented
      further increments. Conversely okadaic acid diminished 1 min increment but did
      not disturb PDCt. It is suggested that the different behaviour of renal PDC from
      fed and starved animals may partly be due to different divalent cation
      independent PDHP phosphatase activity.

PMID- 8569720
TI  - Regulation of phospholamban and troponin-I phosphorylation in the intact rat
      cardiomyocytes by adrenergic and cholinergic stimuli: roles of cyclic
      nucleotides, calcium, protein kinases and phosphatases and depolarization.
AB  - Protein phosphorylation was investigated in [32P]-labeled cardiomyocytes isolated
      from adult rat heart ventricles. The beta-adrenergic stimulation (by
      isoproterenol, ISO) increased the phosphorylation of inhibitory subunit of
      troponin (TN-I), C-protein and phospholamban (PLN). Such stimulation was largely
      mediated by increased adenylyl cyclase (AC) activity, increased myoplasmic cyclic
      AMP and increased cyclic AMP dependent protein kinase (A-kinase)-catalyzed
      phosphorylation of these proteins in view of the following observations: (a)
      dibutyryl-and bromo-derivatives of cyclic AMP mimicked the stimulatory effect of
      ISO on protein phosphorylation while (b) Rp-cyclic AMP was found to attenuate ISO
      dependent stimulation. Unexpectedly, 8-bromo cyclic GMP was found to markedly
      increase TN-I and PLN phosphorylation. Both beta 1- and beta 2-adrenoceptors were
      present and ISO binding to either receptor was found to stimulate myocyte AC.
      However, the stimulation of the beta 2-AR only marginally increased while the
      stimulation of beta 1-AR markedly increased PLN phosphorylation. Other stimuli
      that increase tissue cyclic AMP levels also increased PLN and TN-I
      phosphorylation and these included isobutylmethylxanthine (non-specific
      phosphodiesterase inhibitor), milrinone (inhibits cardiotonic inhibitable
      phosphodiesterase, sometimes called type III or IV) and forskolin (which directly
      stimulates adenylyl cyclase). Cholinergic agonists acting on cardiomyocyte M2
      muscarinic receptors that are coupled to AC via pertussis toxin(PT)-sensitive G
      proteins inhibited AC and attenuated ISO-dependent increases in PLN and TN-I
      phosphorylation. The in vivo PT treatment, which ADP-ribosylated Gi-like
      protein(s) in the myocytes, markedly attenuated muscarinic inhibitory effect on
      PLN and TN-I phosphorylation on one hand and, increased the beta-adrenergic
      stimulation, on the other. Controlled exposure of isolated myocytes to N-ethyl
      maleimide, also led to the findings similar to those seen following the PT
      treatment. Exposure of myocytes to phorbol, 12-myristate, 13-acetate (PMA)
      increased the protein phosphorylation, augmenting the stimulation by ISO, and
      such augmentation was antagonized by propranolol suggesting modulation of the
      beta-adrenoceptor coupled AC pathway by PMA. Okadaic acid (OA) exposure of
      myocytes also increased protein phosphorylation with the results supporting the
      roles for type 1 and 2A protein phosphatases in the dephosphorylation of PLN and
      TN-I. Interestingly OA treatment attenuated the muscarinic inhibitory effect
      which was restored by subsequent brief exposure of myocytes to PMA. While the
      stimulation of alpha adrenoceptors exerted little effect on the phosphorylation
      of PLN and TN-I, inactivation of alpha adrenoceptors by chloroethylclonidine
      (CEC), augmented beta-adrenergically stimulated phosphorylation. KCl-dependent
      depolarization of myocytes was observed to potentiate ISO-dependent increase in
      phosphorylation (incubation period 15 sec to 1 min) as well as to accelerate the
      time-dependent decline in this phosphorylation seen upon longer incubation.
      Verapamil decreased ISO-stimulated protein phosphorylation in the depolarized
      myocytes. Depolarization was found to have little effect on the muscarinic
      inhibitory action on phosphorylation. Prior treatment of myocytes with PMA, was
      found to augment ISO-stimulated protein phosphorylation in the depolarized
      myocytes. Such augmented increases were completely blocked by propranolol.
      Forskolin also stimulated PLN and TN-I phosphorylation. Prior exposure of
      myocytes to forskolin followed by incubation in the depolarized and polarized
      media showed that PLN was dephosphorylated more rapidly in the depolarized
      myocytes. The results support the view that both cyclic AMP and calcium signals
      cooperatively increase the rates of phosphorylation of TN-I and PLN in the
      depolarized cardiomyocytes during beta-adrenergic stimulation. (ABSTRACT
      TRUNCATED)

PMID- 8569723
TI  - Subcellular calcium oscillators and calcium influx support agonist-induced
      calcium waves in cultured astrocytes.
AB  - We have analysed Ca2+ waves induced by norepinephrine in rat cortical astrocytes
      in primary culture using fluorescent indicators fura-2 or fluo-3. The temporal
      pattern of the average [Ca2+]i responses were heterogeneous from cell to cell and
      most cells showed an oscillatory response at concentrations of agonist around
      EC50 (200 nM). Upon receptor activation, [Ca2+]i signals originated from a single
      cellular locus and propagated throughout the cell as a wave. Wave propagation was
      supported by specialized regenerative calcium release loci along the length of
      the cell. The periods of oscillations, amplitudes, and the rates of [Ca2+]i rise
      of these subcellular oscillators differ from each other. These intrinsic kinetic
      properties of the regenerative loci support local waves when stimulation is
      continued over long periods of time. The presence of local waves at specific,
      invariant cellular sites and their inherent kinetic properties provide for the
      unique and reproducible pattern of response seen in a given cell. We hypothesize
      that these loci are local specializations in the endoplasmic reticulum where the
      magnitude of the regenerative Ca2+ release is higher than other regions of the
      cell. Removal of extracellular Ca2+ or blockade of Ca2+ channels by inorganic
      cations (Cd2+ and Ni2+) during stimulation of adrenergic receptors alter the
      sustained plateau component of the [Ca2+]i response. In the absence of Ca2+
      release, due to store depletion with thapsigargin, agonist occupation alone does
      not induce Ca2+ influx in astrocytes. This finding suggests that, under these
      conditions, receptor-operated Ca2+ entry is not operative. Furthermore, our
      experiments provide evidence for local Ca2+ oscillations in cells which can
      support both wave propagation as well as spatially discrete Ca2+ signalling.

PMID- 8569724
TI  - Activation and deactivation of sarcoplasmic reticulum calcium release channels:
      molecular dissection of mechanisms via novel semi-synthetic ryanoids.
AB  - The plant alkaloids ryanodine and dehydroryanodine are high affinity, biphasic
      modulators of the intracellularly located, calcium-regulated calcium release
      channels of a variety of cell types. To date, little is certain about the
      molecular basis of the interactions that prompt low concentrations of ryanodine
      (nanomolar to low micromolar) to activate (open) the channels and higher
      concentrations to deactivate (functionally close) the sarcoplasmic reticulum
      calcium release channel. In the present study, we approached this question using
      novel, semi-synthetic C10-Oeq ester derivatives of ryanodine and dehydroryanodine
      as molecular probes of the ryanodine binding sites on the calcium release
      channel. Binding affinities of these C10-Oeq ester derivatives of ryanodine and
      dehydroryanodine with acidic, basic and neutral side chains (Kd values > 53.9 nM,
      Kd values 0.3-0.7 nM and Kd values 1.3-20.4 nM, compared with 2.3 and 2.8 nM for
      ryanodine and dehydroryanodine, respectively) were evaluated for their ability to
      modulate the patency of the sarcoplasmic reticulum calcium release channel. With
      the exception of only two derivatives tested to date, all the semi-synthetic C10
      Oeq esters selectively activate the Ca2+ release channel. That is, they produce
      no functional closure of the sarcoplasmic reticulum calcium release channels at
      the highest concentration that could be tested. Half-maximal concentrations for
      activation (EC50act values) ranged from 0.87-4.2 microM, compared with an EC50act
      of 1.3 microM for ryanodine. Using a low concentration (0.5 nM) of a high
      specific activity, radioiodinated derivative of ryanodine, C10-Oeq N-(4-azido-5
      125iodo salicyloyl) glycyl ryanodine (1400 Ci/mmol) as the radioligand in
      displacement binding affinity assays, two distinct, sequential ryanodine binding
      isotherms were demonstrated within the normal 0-300 nM ryanodine sigmoidal
      displacement curve. A high affinity site had an IC50 of 0.5 nM (Kd = 0.26 +/-
      0.02 nM). Above this concentration, an apparent plateau occurred between 3 and 6
      nM ryanodine, and at higher concentrations a lower affinity site was revealed
      that demonstrated an IC50 of about 25 nM (Kd = 11.7 +/- 1.2 nM). Scatchard
      analysis from direct binding of C10-Oeq N-(4-azido-5-125iodo salicyloyl) glycyl
      ryanodine to junctional sarcoplasmic reticulum vesicles also suggests the
      presence of more than one class of binding sites within the nanomolar
      concentration range. The high affinity site demonstrated a Bmax of 3 pmol/mg
      protein. We were unable to saturate the lower affinity binding sites with this
      ligand. To evaluate the functional effects occurring among sarcoplasmic reticulum
      calcium release channel monomers as a consequence of ryanodine's binding, we
      utilized a photo-activatable derivative of ryanodine, C10-Oeq N-(4-azido
      salicyloyl) glycyl ryanodine that demonstrates channel modulating characteristics
      similar to ryanodine. Covalently labeling the sarcoplasmic reticulum calcium
      release channels with this ligand, followed by measurements of rates of calcium
      efflux and SDS-PAGE of the labeled protein, revealed that deactivation of the
      sarcoplasmic reticulum calcium release channels of skeletal muscle by this
      ryanoid occurred at concentrations which apparently produce virtually
      irreversibly interactions between receptor monomers. This 'polymerization' was
      indicated by the progressive appearance of two higher molecular weight protein
      bands on SDS-PAGE, concomitant with progressive decreases in the ryanodine
      receptor monomer band that runs at an apparent molecular mass of 365 kDa. In
      summary, we have prepared and utilized novel C10-Oeq ester derivatives of
      ryanodine and dehydroryanodine in studies aimed at better understanding the
      molecular basis for the complex biphasic actions of ryanodine on the sarcoplasmic
      reticulum calcium release channels from rabbit skeletal muscle cells. The
      described studies presage correlations that may be useful in furthering our
      understa

PMID- 8569725
TI  - Inositol lipid-mediated signalling in response to endothelin and ATP in the
      mammalian testis.
AB  - The testis is a complex organ in which local control is achieved by signalling
      between its constituent cells. Herein we describe the responses of cultured rat
      testicular cells and a mouse Sertoli cell-line to stimulation by endothelin and
      ATP, and elsewhere we have shown that rat peritubular myoid cells possess
      phosphoinositidase C-coupled V1a-vasopressin receptors identical to those of
      liver (Howl, J. et al, 1995, Endocrinology 136: 2206-2213). 1. Peritubular myoid
      cells from pre-pubertal rats responded through ETA receptors with PtdIns(4,5)P2
      hydrolysis [EC50 for endothelin-1 (ET-1) approximately 0.4 nM], elevation of
      intracellular [Ca2+], and tyrosine phosphorylation of a variety of cellular
      proteins. They also showed enhanced adenylate cyclase activity, with an EC50 for
      ET-1 of approximately 3 nM, also through ETA receptors. Pharmacological elevation
      of [cAMP] did not immediately change the ET-1-stimulated formation of inositol
      phosphates, but attenuated the response after several hours. 2. Pre-pubertal rat
      Sertoli cells showed no detectable responses to ET-1, but responded to FSH with
      elevated [cAMP] and to ATP with PtdIns(4,5)P2 hydrolysis. PtdIns(4,5)P2
      hydrolysis was equally responsive to ATP and UTP, and so appears to be activated
      by P2U-purinergic receptors. This response was enhanced by protein kinase C
      inhibition and attenuated by PKC activation. 3. Despite its lack of effect on rat
      Sertoli cells in primary culture, ET-1 provoked PtdIns(4,5)P2 hydrolysis in the
      TM4 murine Sertoli cell line (EC50 approximately 0.6 nM), and this response was
      negatively regulated by protein kinase C activation. 5. No receptor-stimulated
      activation of phosphoinositase C was detected in 'germ cell' populations, but the
      non-specific G protein activator A1F4-provoked inositol phosphate accumulation in
      these cells, so demonstrating their potential to respond through yet to be
      identified G protein-coupled receptors with phosphoinositidase C activation. 6.
      Immunoblotting studies showed the presence in rat testis of phosphoinositidase C
      beta 1 and the alpha-subunits(s) of the G-protein(s) Gq and/or G11. These studies
      show that testicular myoid and Sertoli cells use at least three G protein-coupled
      receptors (V1a-vasopressins, ETA-endothelin and P2U-purinergic) to signal through
      phosphoinositidase C activation, that ET-1 can activate multiple signalling
      pathways in myoid cells, and that the ET-1-stimulated phosphoinositidase C
      responses of myoid and Sertoli cells have different regulatory characteristics.

PMID- 8569727
TI  - Second messenger role of magnesium in pancreatic acinar cells of the rat.
AB  - Application of either acetylcholine (ACh, 10(-5) M) or cholecystokinin
      octapeptide (CCK-8, 10(-8) M) to the isolated rat pancreas elicited large
      increases in amylase secretion, radiolabelled 45Ca2+ influx and cytosolic free
      calcium [Ca2+]i levels in zero and normal (1.1 mM) extracellular magnesium
      [Mg2+]o. Elevated [Mg2+]o significantly (p < 0.001) reduced the secretagogue
      evoked secretory responses and Ca2+ mobilisation. Stimulation of pancreatic
      segments with either ACh (10(-5) and 10(-6) M) or CCK-8 (10(-8) and 10(-10) M)
      resulted in marked elevation in Mg2+ concentration in effluent samples (net
      efflux). On removal of either ACh or CCK-8, Mg2+ concentration returned to
      resting level. In pancreatic acinar cells loaded the fluorescent dye magfura, ACh
      and CCK-8 evoked marked reduction in cytosolic free Mg2+ concentration [Mg2+]i
      compared to the resting value of 0.82 +/- 0.03 mM (n = 50) in normal medium in
      the absence of secretagogues. In elevated [Mg2+]o (10 mM) medium, [Mg2+]i rises
      to 0.98 +/- 0.04 mM (n = 6). Addition of CCK-8 led to only a small reduction in
      [Mg2+]i in elevated [Mg2+]o. In Mg2+ loaded pancreatic acinar cells, Mg2+ is
      released in a time dependent manner and this efflux of Mg2+ was sensitive to
      sodium, extracellular amiloride (1 mM), dinitrophenol (10 mM) and lidocaine (1
      mM). The results indicate that Mg2+ is acting as an intracellular messenger to
      regulate the mobilisation of Ca2+ which in turn mediates enzyme secretion.

PMID- 8569726
TI  - PEST sequences in calmodulin-binding proteins.
AB  - Many short-lived proteins which are devoid of proteolytic activity contain PEST
      sequences which are segments along the polypeptide chain that are rich in proline
      (P), glutamate (E), serine (S) and threonine (T). These designated PEST sequences
      are believed to be putative intramolecular signals for rapid proteolytic
      degradation. Calmodulin is a ubiquitous, 17 kDa, acidic Ca(2+)-binding protein
      which plays an important role in the regulation of many physiological processes
      through its interaction with a wide range of calmodulin-binding proteins. Several
      calmodulin-binding proteins are known to contain PEST sequences and are
      susceptible to proteolysis by endogenous neutral proteases such as calpain I and
      calpain II. In this report, we discuss the functions of PEST sequences in
      calmodulin-binding proteins and assess the correlation between calmodulin-binding
      proteins and PEST sequences.

PMID- 8569728
TI  - Evidence for multisite ADP-ribosylation of neuronal phosphoprotein B-50/GAP-43.
AB  - The neuronal phosphoprotein B-50/GAP-43 is associated with neuronal growth and
      regeneration and is involved in the calcium/CaM and G(o) signal transduction
      systems. In particular, B-50 interacts uniquely with CaM by binding in the
      absence of Ca2+. Previously identified as a major neuronal substrate for protein
      kinase C, which releases CaM via phosphorylation, B-50 has more recently been
      shown to be a substrate for endogenous ADP-ribosyltransferases. In the present
      study, we utilized amino acid modification with iodoacetamide and chemical
      stability to mercury and neutral hydroxylamine to demonstrate that the
      predominant site of ADP-ribosylation is Cys 3 and/or Cys 4. Chymotryptic peptide
      mapping further revealed a second, less labelled site of ribosylation in the C
      terminal region. The results also demonstrate that, in contrast to PKC
      phosphorylation, ADP-ribosylation of B-50 does not mediate CaM binding. Since Cys
      3 and Cys 4, by palmitoylation, are important for membrane anchoring, our
      findings suggest that ADP-ribosylation of B-50 may have a role in directing the
      intracellular localization of the protein. Hence, ribosylation of B-50 may
      mediate where B-50 interacts with signal transduction pathways.

PMID- 8569729
TI  - Mammalian myristoyl CoA: protein N-myristoyltransferase.
AB  - Myristoyl CoA:Protein N-myristoyltransferase (NMT) is the enzyme which catalyses
      the covalent transfer of myristate from myristoyl CoA to the amino-terminal
      glycine residue of protein substrates. Although NMT is ubiquitous in eukaryotic
      cells, the enzyme levels and cellular distribution vary among tissues. In this
      article, we describe the properties of mammalian NMT(s) with reference to
      subcellular distribution, molecular weights, substrate specificity and the
      possible involvement of NMT in pathological processes. The cytosolic fraction of
      bovine brain contains majority of NMT activity. In contrast, rabbit colon and rat
      liver NMT activity was predominantly particulate. Regional differences in NMT
      activity have been observed in both rabbit intestine and bovine brain. Results
      from our laboratory along with the existing knowledge, provide evidence for the
      existence of tissue specific isozymes of NMT.

PMID- 8569730
TI  - Towards the molecular basis for the regulation of mitochondrial dehydrogenases by
      calcium ions.
AB  - In mammalian cells, increases in calcium concentration cause increases in
      oxidative phosphorylation. This effect is mediated by the activation of four
      mitochondrial dehydrogenases by calcium ions; FAD-glycerol 3-phosphate
      dehydrogenase, pyruvate dehydrogenase, NAD-isocitrate dehydrogenase and
      oxoglutarate dehydrogenase. FAD-glycerol 3-phosphate dehydrogenase, being located
      on the outer surface of the inner mitochondrial membrane, is exposed to
      fluctuations in cytoplasmic calcium concentration. The other three enzymes are
      located within the mitochondrial matrix. While the kinetic properties of all of
      these enzymes are well characterised, the molecular basis for their regulation by
      calcium is not. This review uses information derived from calcium binding
      studies, analysis of conserved calcium binding motifs and comparison of amino
      acid sequences from calcium sensitive and non-sensitive enzymes to discuss how
      the recent cloning of several subunits from the four dehydrogenases enhances our
      understanding of the ways in which these enzymes bind calcium. FAD-glycerol 3
      phosphate dehydrogenase binds calcium ions through a domain which is part of the
      polypeptide chain of the enzyme. In contrast, it is possible that the calcium
      sensitivity of the other three dehydrogenases may involve separate calcium
      binding subunits.

PMID- 8569731
TI  - Regulation of cellular Gs alpha levels and basal adenylyl cyclase activity by
      expression of the beta 2-adrenoceptor in neuroblastoma cell lines.
AB  - Mouse neuroblastoma x rat glioma hybrid NG 108-15 and mouse neuroblastoma x
      embryonic hamster brain NCB20 cells were transfected with a construct containing
      a human beta 2 adrenoceptor cDNA under the control of the beta actin promoter.
      Clones were selected on the basis of resistance to geneticin sulphate and those
      expressing a range of levels of the receptor expanded for further study.
      Membranes from a clone of NG108-15 cells expressing high levels of the receptor
      (beta N22) but not one expressing only low levels of the receptor (beta N17)
      exhibited a markedly elevated adenylyl cyclase activity when measured in the
      presence of Mg2+ compared to wild type cells. This was not due to elevated levels
      of the adenylyl cyclase catalytic moiety however as there was no difference in
      these membranes when the adenylyl cyclase activity was measured in the presence
      of Mn2+. The elevated basal activity was partially reversed by addition of the
      beta-adrenoceptor antagonist propranolol. Agonist activation of beta N22 but not
      beta N17 cells led to a large selective down-regulation of cellular Gs alpha
      levels which was independent of the generation of cyclic AMP. Isoprenaline
      stimulation of adenylyl cyclase activity and of the specific high affinity
      binding of [3H] forskolin was achieved with substantially greater potency (some
      30 fold) in beta N22 cell membranes than in beta N17. By contrast agonist
      activation of the endogenously expressed IP prostanoid receptor caused
      stimulation of adenylyl cyclase and stimulation of high affinity [3H] forskolin
      binding which was equipotent in each of beta N22, beta N17 and wild type NG108-15
      cells. Agonist activation of the IP prostanoid receptor caused an equivalent
      degree of Gs alpha down-regulation in each cell type. Expression of an epitope
      tagged variant of Gs alpha in NG108-15 cells resulted in prostanoid agonist
      induced down-regulation of this polypeptide in a manner indistinguishable from
      that of wild type Gs alpha. Isolation of clones of NCB20 cells expressing high
      levels of the beta 2 adrenoceptor also resulted in a specific agonist-induced
      down-regulation of Gs alpha.

PMID- 8569732
TI  - Membrane phospholipids and adrenergic receptor function.
AB  - We have reviewed the effects on adrenergic receptors by membrane phospholipid
      alterations secondary to oxidative stress and phospholipases' activity.
      Experimental evidences indicate that the function of both alpha- and beta
      adrenoceptors is regulated by their phospholipid microdomain; however, the
      underlying mechanism is still undefined. No information seems to be available on
      the influence of phospholipids on alpha 2-adrenoceptors and on all adrenoceptors'
      subtypes. Thus, further studies are necessary to clarify the role of membrane
      phospholipids in regulating the function of each member of the adrenergic
      receptor superfamily.

PMID- 8569733
TI  - Defective ANF-R2/ANP-C receptor-mediated signalling in hypertension.
AB  - In the present studies we have shown that atrial natriuretic factor (peptide)
      receptor of ANF-R2/ANP-C type is coupled to adenylyl cyclase/cAMP signal
      transduction system through Gi-regulatory protein and is implicated in mediating
      some of the physiological responses of atrial natriuretic factor or peptide
      (ANP). ANF-R2/ANP-C receptor-mediated adenylyl cyclase inhibition was altered in
      hypertension. This alteration was tissue specific. In heart, aorta, brain and
      adrenal, the extent of inhibition of adenylyl cyclase by ANP was enhanced in SHR
      as compared to age-matched WKY, whereas in platelets, the ANP-mediated inhibition
      was completely attenuated. The enhanced inhibition of adenylyl cyclase by ANP was
      also observed in heart and aorta from DOCA-salt hypertensive rats. In addition,
      the augmented inhibition of adenylyl cyclase by ANP was observed in 2 weeks and
      older SHR but not in 3-5 days old SHR. Similarly, in DOCA-salt hypertensive rats,
      the enhanced inhibition of adenylyl cyclase by ANP was observed after 2 weeks of
      DOCA-salt treatment when the blood pressure was also enhanced, however one week
      older SHR but not in 3-5 days old SHR. Similarly, in DOCA-salt hypertensive rats,
      the enhanced inhibition of adenylyl cyclase by ANP was observed after 2 weeks of
      DOCA-salt treatment when the blood pressure and augmented ANP-mediated inhibition
      of adenylyl of DOCA-salt treatment did not result in an augmented blood pressure
      and augmented ANP-mediated inhibition of adenylyl cyclase, suggesting that blood
      pressure increase may be responsible for the enhanced responsiveness of ANP to
      adenylyl cyclase inhibition. However, in genetic model of hypertension, the
      increased inhibition of adenylyl cyclase by ANP at 2 weeks of age (when the blood
      pressure is normal) may be implicated in the pathogenesis of hypertension. The
      augmented inhibition of adenylyl cyclase in cardiovascular tissues from SHR and
      DOCA-salt hypertensive rats may be due to the upregulation of ANF-R2/ANP-C
      receptors or due to the amplification of post-receptor signalling mechanisms.

PMID- 8569735
TI  - Signal transduction: regulation of cAMP concentration in cardiac muscle by
      calmodulin-dependent cyclic nucleotide phosphodiesterase.
AB  - The bovine heart calmodulin-dependent phosphodiesterase can be phosphorylated by
      cAMP-dependent protein kinase, resulting in a decrease in the enzyme's affinity
      for calmodulin. The phosphorylation of calmodulin-dependent phosphodiesterase is
      blocked by Ca2+ and calmodulin and reversed by the calmodulin-dependent
      phosphatase. The dephosphorylation is accompanied by an increase in the affinity
      of the phosphodiesterase for calmodulin. The CaM-dependent phosphodiesterase
      isozymes of heart and brain are regulated by calmodulin, but the affinity for
      calmodulin are different. Furthermore, the bovine heart CaM-dependent
      phosphodiesterase isozyme in stimulated at much lower Ca2+ concentration than the
      bovine brain isozymes. Results from this study suggest that the activity of this
      phosphodiesterase is precisely regulated by cross-talk between Ca2+ and cAMP
      signalling pathways.

PMID- 8569734
TI  - Excitatory amino acid receptor-mediated neuronal signal transduction: modulation
      by polyamines and calcium.
AB  - The excitatory amino acids (EAA), L-glutamate and L-aspartate were initially
      advanced as excitatory neurotransmitters some 30 years ago but in the past few
      years investigations on EAA have proceeded rapidly from the identification of the
      putative neurotransmitters and characterization of their receptors to the
      clarification of their role in development, learning, memory, and neuropathology.
      The NMDA(N-methyl-D-aspartate) class of glutamate receptor has been the subject
      of much recent interdisciplinary study, as NMDA receptors render over stimulated
      neurons susceptible to injury and death. This review is focused on the
      involvement of polyamines in EAA receptor-mediated neuronal signal transduction
      mechanisms.

PMID- 8569736
TI  - On the role of nitric oxide as a cellular messenger in brain.
AB  - The characteristics of the high-affinity uptake of [3H]-L-arginine into
      cerebellar and cortical synaptosomes were investigated. Uptake into cerebellar
      synaptosomes was often greater than seen in cortical synaptosomes under similar
      experimental conditions, and this was reflected by a higher Vmax in synaptosomes
      from this brain region. Uptake into synaptosomes prepared from both brain regions
      was markedly enhanced by removing extracellular Na+, adn inhibited by high
      concentrations of extracellular K+. Depolarisation with 4-aminopyridine or
      veratridine has no effect on uptake. Uptake was also unaffected by
      hyperpolarisation. The profile of inhibition of arginine uptake by related amino
      acids was similar to that seen for the y+ carrier, but the other characteristic
      alluded to above suggest that the carrier is distinct from the classical y+
      system. The possible relationship between the carrier and the metabolism of
      arginine through the nitric oxide [NO] pathway, and the role of NO in the central
      nervous system is discussed.

PMID- 8569738
TI  - Interaction of heavy metal toxicants with brain constitutive nitric oxide
      synthase.
AB  - This study was designed to evaluate the in vitro effects of transition heavy
      metal cations on activity of constitutive isoform of nitric oxide synthase (cNOS)
      in rat brain. NOS activity was determined in the cytosolic fractions of rat
      cerebral hemispheres by conversion of 3H-L-arginine to 3H-L-citrulline. Different
      concentrations of mercury (Hg2+), nickel (Ni2+), manganese (Mn2+), zinc (Zn2+),
      cadmium (Cd2+), lead (Pd2+) and calcium (Ca2+) were tested on NOS activity. While
      all the cations caused inhibition, there were differences in the apparent
      inhibition constants (Ki) among the cations. With the exception of calcium ion no
      other cation required preincubation with the enzyme preparation. These results
      indicate that while calcium ion modulate cNOS activity at regulatory site(s),
      inhibitory influence of toxic heavy metal cations may be exerted on the catalytic
      site(s) either by direct binding to it or by interfering with the electron
      transfer during catalysis.

PMID- 8569737
TI  - Oxygen-radical/nitric oxide mediate calcium-dependent hormone action on cyclic
      GMP system: a novel concept in signal transduction mechanisms.
AB  - The broad objective of these studies was to understand the nature of cyclic GMP
      system and the mechanism(s) whereby hormone, autacoids and drugs alter this
      signal in various physiological systems. Studies were undertaken on the
      modulation of guanylate cyclase activity by oxygen-radicals/nitric oxide and the
      mechanism(s) of generation of nitric oxide by receptor-selective hormones. We
      observed that cytosolic guanylate cyclase undergoes significant stimulation in
      the presence of oxygen-radicals/nitric oxide. This activation by nitric oxide can
      be reversed by hemeproteins, thus, enabling guanylate cyclase system to cycle
      between activated and deactivated state. The evidence is presented that oxygen
      radicals are required for the synthesis of nitric oxide by NO synthase as
      demonstrated by inhibition of NO formation by oxygen-radical scavengers. And
      finally, the data is presented that acetylcholine-induced elevations of
      intracellular levels of cyclic GMP can be attenuated by muscarinic antagonist,
      atropine and superoxide anion scavenger, nitroblue tetrazolium. These
      observations establish a novel concept that activation of hormone receptors on
      the cell surface, triggers generation of oxygen radicals and hydrogen peroxide
      which participates in the catalytic conversion of L-arginine to nitric oxide by
      nitric oxide synthase in the presence of calcium ion. The oxygen-radicals/NO,
      thus formed, oxidatively activate guanylate cyclase and transduce the message of
      calcium-dependent hormones.

PMID- 8569739
TI  - Mediation of H2O2-induced vascular relaxation by endothelium-derived relaxing
      factor.
AB  - We investigated the effects of H2O2 generated by glucose (G) and glucose glucose
      oxidase (GO) on the isolated rabbit aorta suspended in Krebs-Ringer solution.
      H2O2 produced contraction in small concentration and relaxation followed by
      contraction in large concentration. Contraction produced by large concentration
      was smaller than that produced by small concentration of H2O2. Relaxation was
      prevented by deendothelialization or NG-monomethyl-L-arginine, an inhibitor of
      nitric oxide synthesis. These results suggest that H2O2 in large concentrations
      produces relaxation followed by contraction, and that the relaxation is
      endothelium-dependent and is mediated by nitric oxide, an endothelium-derived
      relaxing factor.

PMID- 8569740
TI  - The cyclic AMP system and Drosophila learning.
AB  - The cyclic AMP (cAMP) system plays a critical role in olfactory learning in the
      fruit fly, Drosophila melanogaster, as evidenced by the following: [1] The dunce
      gene encodes a form of cAMP phosphodiesterase (PDE). Flies carrying mutations at
      this gene show reduced PDE activity, high cAMP levels, and deficits in olfactory
      learning and memory [2]. The rutabaga gene encodes one type of adenylyl cyclase
      (AC) similar in properties to the Type I AC characterized from vertebrate brain.
      This enzyme is activated by G-protein and Ca++ and has been postulated to be a
      molecular coincidence detector, capable of integrating information from two
      independent sources such as the conditioned stimulus (CS) and the unconditioned
      stimulus (US) delivered to animals during Pavlovian conditioning. Rutabaga mutant
      flies are deficient in AC activity and show behavioral defects similar to those
      exhibited by dunce mutants [3]. Flies carrying mutations in the gene (DC0) that
      encodes the catalytic subunit of protein kinase A (PKA), the major mediator of
      cAMP actions, show alterations in learning performance and a loss in PKA
      activity. All three genes are expressed preferentially in mushroom bodies,
      neuroanatomical sites that mediate olfactory learning. Interestingly, the PDE and
      the catalytic subunit of PKA are found primarily in axonal and dendritic
      compartments of the mushroom body cells, whereas the AC is found primarily in the
      axonal compartment. The reason for this differential compartmentalization is
      unclear, although the hypothetical role of AC as coincidence detector would
      predict that CS and US stimuli are integrated in the axonal compartment. These
      observations suggest that cAMP is a dominant second messenger utilized by
      mushroom body cells to modulate their physiology while the animal is learning and
      consolidating memory. However, many other types of molecules are likely involved
      in the physiological alterations that occur in these cells during learning,
      including cell surface proteins, transcription factors, and synaptic proteins.

PMID- 8569742
TI  - Disturbances in signal transduction mechanisms in Alzheimer's disease.
AB  - Many of the treatments directed towards alleviation of symptoms in Alzheimer's
      disease assume that target receptor systems are functionally intact. However,
      there is now considerable evidence that this is not the case. In human post
      mortem brain tissue samples, the function of the GTP-binding protein Gs in
      regulating adenylyl cyclase is severely disabled, whereas that of Gi is intact.
      This difference in the function of the two G-protein types is also found in G
      protein regulation of high- and low-affinity receptor recognition site
      populations. Measurement of G-protein densities using selective antibodies has
      indicated that the dysfunction in Gs-stimulation of cAMP production correlates
      with the ratio of the large to small molecular weight isoforms of the Gs alpha
      subunit. With respect to intracellular second messenger effects, there is a
      dramatic decrease in the density of brain receptor recognition sites for
      Ins(1,4,5)P3 that is not accompanied by a corresponding change in the
      Ins(1,3,4,5)P4 recognition site density. Protein kinase C function is also
      altered in Alzheimer's disease, a finding that may be of importance for the
      control of beta-amyloid production. These studies indicate that signal
      transduction processes are severely compromised in Alzheimer's disease. Some of
      these disturbances are also seen in cultured fibroblasts from Alzheimer's disease
      patients, indicating that they are neither restricted to areas of
      histopathological change, nor non-specific changes found late in the course of
      the disease. Cellular models to investigate the relation between amyloid
      production and deficits in signal transduction are also discussed.

PMID- 8569743
TI  - High molecular weight calmodulin-binding protein is phosphorylated by calmodulin
      dependent protein kinase VI from bovine cardiac muscle.
AB  - A high molecular weight calmodulin-binding protein (HMW CaMBP) from bovine heart
      cytosolic fraction was purified to apparent homogeneity. A novel CaM-dependent
      protein kinase was originally discovered when the total CaM-binding protein
      fraction from cardiac muscle was loaded on a gel filtration column. The CaM
      dependent protein kinase was shown by gel filtration chromatography to have an
      apparent molecular mass of 36,000 daltons. The CaM-dependent protein kinase has
      been highly purified by sequential chromatography on DEAE-Sepharose Cl 6B (to
      remove calmodulin), CaM-Sepharose 4B, phosphocellulose, Sepharose 6B gel
      filtration and Mono S column chromatographies. The highly purified protein kinase
      stoichiometrically phosphorylated the HMW CaMBP in a Ca2+/CaM-dependent manner.
      The phosphorylation resulted in the maximal incorporation of 1 mol of
      phosphate/mol of the HMW CaMBP. The distinct substrate specificity of this
      protein kinase indicates that it is not related to the known protein kinases (I,
      II, III, IV and V) that have been already characterized, therefore we would like
      to designate this novel kinase as a CaM-dependent protein kinase VI.

PMID- 8569741
TI  - The biochemistry of learning and memory.
AB  - An overview of some of the biochemical and molecular events involved in the
      process of learning and memory are presented in a short review. Two invertebrate
      models of learning are considered: the gill-withdrawal reflex of Aplysia and
      avoidance learning in Drosophila melanogaster. Particular attention is paid to
      the biochemical mechanisms underlying both the development of long-term
      potentiation (LTP) and passive avoidance learning (PAL) in the young chick. The
      role of several biological molecules in learning and memory are considered, for
      example, protein kinase C (PKC), Ca(++)-Calmodulin kinase II (CaMKII), GAP-43,
      and glutamate receptors.

PMID- 8569744
TI  - Functional and genetic analysis of annexin VI.
AB  - This study is concerned with the determination of the function of the 68kDa
      calcium-binding protein, annexin VI. Studies on the structure and regulation of
      the gene include a detailed analysis of annexin VI expressed heterologously in
      human A431 carcinoma cells. We have recently discovered that annexin VI is
      subject to a novel growth dependent post-translational modification.
      Interestingly, the protein exerts a negative effect on A431 cells. This effect
      was manifested as a partial reversal of the transformed phenotype. We are
      currently exploring the hypothesis that the post-translational modification of
      annexin VI is required for sub-cellular targeting, and that correct localisation
      within the cell is essential for function.

PMID- 8569745
TI  - Protein engineering and NMR studies of calmodulin.
AB  - The calcium regulatory protein calmodulin (CaM) plays a role as an on-off switch
      in the activation of many enzymes and proteins. CaM has a dumbbell shaped
      structure with two folded domains, which are connected by a flexible linker in
      solution. The calmodulin-binding domains of the target proteins are contained in
      20 residue long amino acid sequences, that share no obvious amino acid sequence
      homology. In this contribution, we discuss the features of CaM, which allow it to
      be rather promiscuous, and bind effectively to all these distinct domains. In
      particular, we describe the role of the methionine-rich hydrophobic surfaces of
      the protein in providing a malleable and sticky surface for binding many
      hydrophobic peptides. The enzyme activation properties of various Met --> Leu
      mutants of CaM are discussed. In addition, the role of the flexible linker region
      that connects the two domains is also analyzed. Finally, we describe various NMR
      and spectroscopic experiments that aid in determining the CaM-bound structures of
      synthetic peptides containing various CaM-binding domains. All structures
      analyzed to date are alpha-helical when bound to CaM, and they interact with CaM
      only through amino acid sidechains. This form of protein-protein interaction is
      rather unique, and may contribute to CaM's capacity to bind effectively to such a
      wide range of distinct partners.

PMID- 8569747
TI  - Regulatory properties of neuronal cdc2-like kinase.
AB  - Neuronal cdc2-like kinase, nclk, is a heterodimer of cyclin dependent protein
      kinase 5, cdk5, and a 25 kDa subunit derived from a novel, neuron-specific, 35
      kDa protein: p35. The characterization and regulation of nclk will be summarized
      in this minireview. The activity of nclk appears to be governed by highly complex
      regulatory mechanisms including protein-protein interaction, protein
      phosphorylation and isoforms. The histone H1 kinase activity of nclk is
      absolutely dependent of the interaction between the 25 kDa subunit and the
      catalytic subunit, cdk5. In addition, nclk interacts with other cellular proteins
      to form macromolecular complexes. The kinase activity of nclk is inhibited in
      vitro by the phosphorylation reactions of a weel-like protein tyrosine kinase and
      a protein serine/threonine kinase from bovine thymus. Northern blot analysis has
      revealed the existence of two populations of p35 mRNA of 2 and 4 kb. A novel cDNA
      encoding a p35 homologous protein has been obtained from a human hippocampus
      library.

PMID- 8569749
TI  - Modulation of protein kinase C by adenosine: involvement of adenosine A1 receptor
      pertussis toxin sensitive nucleotide binding protein system.
AB  - The objective of this study was to determine whether adenosine A1 or A2 receptor
      was responsible for the regulation of protein kinase C (PKC) in porcine coronary
      artery and its coupling to G-protein. Endothelium denuded arterial rings were
      incubated with PDBu (200 nM) in the presence or absence of adenosine receptor
      agonists and antagonists for 1 day. Following incubation, the arterial rings were
      contracted with increasing concentrations of endothelin-1 (ET-1) (10(-10)-10(-7)
      M). Arteries incubated with PDBu alone failed to produce contraction in response
      to ET-1. On the contrary, inclusion of A1 receptor agonist ENBA at 10(-9) M in
      the incubation media with PDBu protected against the PDBu induced blunting of the
      ET-1 contractions by 50%. Incubation with ENBA alone increased ET-1 dependent
      contractions by about 2 fold. Inclusion of A1 receptor antagonist, N0861 at 10(
      6) M along with PDBu and ENBA, completely blocked the protective effect of ENBA
      against the PDBu induced attenuation of ET-1 contractions. N0861 also completely
      blocked the increase in ET-1 contractions in the arterial rings incubated with
      ENBA alone. Another A1 receptor antagonist DPCPX also produced similar results as
      N0861. On the contrary, arterial rings incubated with relatively specific A2
      receptor agonist CGS 21680 at 10(-4) M did not produce any protection against
      PDBu induced blunting of the ET-1 contractions. Incubation with CGS 21680 alone
      also did not significantly alter the ET-1 contractions. Interestingly, inclusion
      of A2 receptor antagonist DMPX at 10(-4) M in the incubation media along with CGS
      21680 mimicked the effects of ENBA alone i.e. produced protection against PDBu
      and enhanced ET-1 contractions. Incubation of the arteries with ENBA alone caused
      an accumulation of PKC levels, whereas, incubation with CGS 21680 had no
      significant effect on PKC levels. To study the coupling of adenosine receptor
      with G-protein, the tissue was incubated for one day with cholera (CT) or
      pertussis toxin (PT) in the presence or absence or ENBA and PDBu as described
      above. Incubation with PT blocked the protective effect of ENBA against PDBu as
      well as the elevation of ET-1 response when incubated with ENBA alone. On the
      contrary, incubation with CT did not produce any significant effect on ENBA
      responses. These results indicate that PKC is modulated by adenosine via A1
      adenosine receptors and through a PT sensitive G-protein.

PMID- 8569750
TI  - Phosphorylation and partial sequence of pregnant sheep myometrium myosin light
      chain kinase.
AB  - The function of the uterine smooth muscle in gestation and parturition is
      affected by a variety of hormones and biomolecules, some of which alter the
      intracellular levels of cAMP and Ca2+. Since the activity of smooth muscle MLCK
      has been shown to be modulated by phosphorylation, the effect of this
      modification of pregnant sheep myometrium (psm) MLCK by the catalytic subunit of
      cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) was studied. In
      contrast to other smooth muscle MLCK reported, PKA incorporates 2.0-2.2 moles
      phosphate into a mole of psm MLCK both in the presence and absence of Ca(2+)
      calmodulin. Modification of serine residues inhibited the activity of the enzyme.
      PKC also incorporated 2.0-2.1 moles of phosphate per mole psmMLCK under both
      conditions but had no effect on the MLCK activity. Sequential phosphorylation by
      PKC and PKA incorporated 3.8-4.1 moles phosphate suggesting that the amino acid
      residues modified by the two kinases are different. Phosphoamino acid analysis of
      the MLCK revealed that PKC phosphorylated serine and threonine residues. The
      double reciprocal plots of the enzyme activity and calmodulin concentrations
      showed that the Vmax of the reaction is not altered by phosphorylation by PKA but
      the calmodulin concentration require for half-maximal activation is increased
      about 4-fold. Only 10 out of 17 monoclonal antibodies to various regions of the
      turkey gizzard MLCK cross-reacted with psmMLCK suggesting structural differences
      between these enzymes. Comparison of the deduced amino acid sequence of the cDNA
      encoding the C-terminal half of the psmMLCK molecule showed that while cgMLCK and
      psmMLCK are highly homologous, a number of nonconservative substitutions are
      present, particularly near the PKA phosphorylation site B (S828).

PMID- 8569748
TI  - Post-translationally modified 14-3-3 isoforms and inhibition of protein kinase C.
AB  - This report compares the ability of individual members of the 14-3-3 protein
      family to inhibit particular protein kinase C (PKC) isoforms. We also show that
      two of these 14-3-3 isoforms (alpha and delta) specific to mammalian and avian
      brain are in vivo post-translationally modified forms of beta and zeta
      respectively. The presence of this modification enhances the activity of 14-3-3
      as an inhibitor of protein kinase C nearly two fold. A method for analysing
      isoforms of 14-3-3 on acid-urea gels is also described. This permits the complete
      separation of all major isoforms and their unequivocal identification by a range
      of isoform specific antisera. The activity of recombinant 14-3-3 and isoforms
      renatured by a novel method after separation by reverse phase HPLC are compared.
      The effects of diacylglycerol and the phorbol ester, PMA (phorbol 1 2-myristate
      13 acetate) on the inhibition suggest that one of the sites of interaction of 14
      3-3 may be the cysteine-rich (C1) domain in PKC.

PMID- 8569746
TI  - Annexin II tetramer: structure and function.
AB  - The annexins are a family of proteins that bind acidic phospholipids in the
      presence of Ca2+. The interaction of these proteins with biological membranes has
      led to the suggestion that these proteins may play a role in membrane trafficking
      events such as exocytosis, endocytosis and cell-cell adhesion. One member of the
      annexin family, annexin II, has been shown to exist as a monomer, heterodimer or
      heterotetramer. The ability of annexin II tetramer to bridge secretory granules
      to plasma membrane has suggested that this protein may play a role in Ca(2+)
      dependent exocytosis. Annexin II tetramer has also been demonstrated on the
      extracellular face of some metastatic cells where it mediates the binding of
      certain metastatic cells to normal cells. Annexin II tetramer is a major cellular
      substrate of protein kinase C and pp60src. Phosphorylation of annexin II tetramer
      is a negative modulator of protein function.

PMID- 8569751
TI  - Effects of pyruvate on pyruvate dehydrogenase kinase of rat heart.
AB  - Sensitivity of rat heart pyruvate dehydrogenase kinase (PDHK) to pyruvate
      inhibition was tested under various conditions using pyruvate dehydrogenase
      complex (PDC) in mitochondria (mPDC) and in a high speed precipitate of whole
      tissue homogenates (hPDC). In the latter preparation pyruvate in the range of
      concentration 1-10 mM caused increasing inhibition of PDHK when the enzyme was
      prepared from animals fed ad libitum but had no effect when the enzyme was
      prepared from 48 h starved animals. Similar behaviour was observed in mPDC from
      fed and starved animals when rotenone was present, pyruvate at 1 mM concentration
      stimulated PDHK from hearts of fed animals but was without effect at 10 mM. When
      mPDC or hPDC from hearts of starved animals was incubated at 30 degrees C for 30
      min, inhibition of PDHK by pyruvate was restored.

PMID- 8569752
TI  - Tyrosine kinase-mediated signal transduction pathways and the actions of
      polypeptide growth factors and G-protein-coupled agonists in smooth muscle.
AB  - This synopsis focuses on the role that tyrosine kinase pathways may play in the
      acute regulation of smooth muscle contractility by receptor-kinase-activating
      growth factors, such as epidermal growth factor-urogastrone (EGF-URO) and by G
      protein-coupled agonists, such as angiotensin-II. Growth factor-activated
      response paradigms that modulate smooth muscle contractility are summarized and
      the parallels between the actions of G-protein-coupled agonists and growth
      factors in these response systems are pointed out. A possible dynamic interplay
      between tyrosine kinase and tyrosine phosphatase activities to modulate tissue
      tension is also hypothesized. Finally, a model is proposed, wherein an
      intermediary tyrosine kinase pathway is suggested as a point of convergence for
      the regulation of smooth muscle contractility by agonists as diverse as EGF-URO
      and angiotensin-II.

PMID- 8569753
TI  - Protein tyrosine phosphorylation in cardiovascular system.
AB  - Protein tyrosine phosphorylation is believed to play a central role in signaling
      pathways initiated by growth factor receptor activation. Recent studies have
      shown that various vasoactive peptides, in addition to eliciting a contractile
      response, also serve as growth factors for vascular smooth muscle ans stimulate
      tyrosyl phosphorylation of several endogenous proteins. Some of these proteins
      have been identified and are similar to those stimulated by growth factor
      receptor activation. Furthermore, evidence is also accumulating to support an
      involvement of protein tyrosine phosphorylation in acute action of growth factors
      and vasoactive peptides on smooth an muscle contractility. This review still
      briefly summarize the recent work on vasoactive peptide-mediated protein tyrosine
      phosphorylation in cardiovascular tissues and its potential functional
      significance.

PMID- 8569754
TI  - Regulation of glycogen synthase activation in isolated hepatocytes.
AB  - Glycogen synthase, the regulatory enzyme of glycogen synthesis undergoes
      multisite phosphorylation leading to its inactivation. The kinases responsible
      for this covalent modification (ex. cAMP-dependent protein kinase, protein kinase
      C and glycogen synthase kinase-3) are controlled by the second messengers
      generated by different hormones. The isolated hepatocytes has been used as one of
      the experimental models for studying this complex regulatory process.
      Inactivation of glycogen synthase by glucagon and vasopressin has been shown to
      be accompanied with incorporation of phosphate into the enzyme protein. Insulin
      has been shown to activate glycogen synthase by inhibition of kinases and
      activation of synthase phosphatase. Glycogen synthase is activated by several
      gluconeogenic substrates, in addition to glucose. Studies in hepatocytes with
      activators and inhibitors of protein kinase C show that this enzyme negatively
      controls glycogen synthase. The differential effects of the phosphatase
      inhibitors, calyculin A and okadaic acid in liver cells provide supporting
      evidence that protein phosphatase type-1 plays a major role in the regulation of
      glycogen synthase. Hepatocytes isolated from diabetic rats of both types (insulin
      dependent and non-insulin-dependent) mimic the defective glycogen synthase
      activation seen in vivo.

PMID- 8569755
TI  - Protein kinase C beta from Friend erythroleukemia cells is associated with
      chromatin and DNA.
AB  - Certain protein kinase C (PKC) isotypes are localized to the nucleus during
      cellular proliferation in murine erythroid cells, as well as in human
      promyelocytic leukemia and erythroleukemia cells. Because the structure of these
      PKC isotypes contains a conserved cysteine-rich region that contains the zinc
      finger DNA binding motif, we tested the hypothesis that selected PKC isotypes
      found in Friend erythroleukemia cells can bind to DNA. Cell lysates from murine
      Friend erythroleukemia cells, which express alpha, beta I, and beta II PKC,
      expressed greater amounts of the beta isoforms than the alpha isoform of PKC in
      their nuclei, and PKC beta I was found in the chromatin of these cells. Lysates
      of these cells were tested for their ability to bind to a DNA-cellulose column.
      Bound proteins were eluted with a step gradient of increasing KCl concentrations,
      and eluant fractions were then subjected to immunoblot analysis using isotype
      specific antibodies to the alpha and beta I isotypes of PKC. DNA binding was
      detected for the PKC beta I isotype, which is present in the nucleus, but not for
      the more abundant PKC alpha isotype, which resides primarily in the cytoplasm.
      These results demonstrate that PKC can associate with DNA, and that this
      association is isotype specific in Friend erythroleukemia cells.

PMID- 8569756
TI  - Lipid peroxidation and activity of antioxidant enzymes in diabetic rats.
AB  - We hypothesized that oxygen free radicals (OFRs) may be involved in pathogenesis
      of diabetic complications. We therefore investigated the levels of lipid
      peroxidation by measuring thiobarbituric acid reactive substances (TBARS) and
      activity of antioxidant enzymes [superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px) and catalase (CAT)] in tissues and blood of streptozotocin
      (STZ)-induced diabetic rats. The animals were divided into two groups: control
      and diabetic. After 10 weeks (wks) of diabetes the animals were sacrificed and
      liver, heart, pancreas, kidney and blood were collected for measurement of
      various biochemical parameters. Diabetes was associated with a significant
      increase in TBARS in pancreas, heart and blood. The activity of CAT increased in
      liver, heart and blood but decreased in kidney. GSH-Px activity increased in
      pancreas and kidney while SOD activity increased in liver, heart and pancreas.
      Our findings suggest that oxidative stress occurs in diabetic state and that
      oxidative damage to tissues may be a contributory factor in complications
      associated with diabetes.

PMID- 8569757
TI  - N-3 and n-6 fatty acid metabolism in undifferentiated and differentiated human
      intestine cell line (Caco-2).
AB  - Metabolism of n-6 and n-3 fatty acids in the undifferentiated and differentiated
      human adenocarcinoma colon cell line (Caco-2) was studied. In cells incubated
      with either 18:2n-6 or 18:3n-3, no significant amounts of long chain n-6 and n-3
      metabolites were found. Incubation with either 18:3n-6 or 18:4n-3 raised
      significantly the levels of 20:3n-6 and 20:4n-3, respectively. In the
      undifferentiated cells, significant proportions of 20:3n-6 and 20:4n-3 were
      further delta 5-desaturated to form 20:4n-6 and 20:5n-3, respectively. Incubation
      with either 20:4n-6 or 20:5n-3 raised the levels of their direct elongation
      products, 22:4n-6 and 22:5n-3, respectively. Incubation with 22:4n-6 or 22:5n-3
      increased the levels of 20:4n-6 and 20:5n-6. These results suggest that delta 6
      desaturation in the Caco-2 cells is less active in comparison with elongation,
      delta 5-desaturation and retro-conversion. These enzymes were modulated by the
      state of differentiation, and appeared to be non-specific to n-3 and n-6 fatty
      acids. When cells were incubated with 18:3n-6 and 18:4n-3 concomitantly, the
      levels of incorporation of total n-6 fatty acids into cellular lipids were
      greater than those of the n-3 fatty acids, whereas the ratios of 20+22 carbon
      metabolites to 18-carbon precursor favored n-3 over n-6 fatty acids. These
      results suggest that n-3 and n-6 fatty acids were not metabolized identically in
      Caco-2 cells.

PMID- 8569758
TI  - Oxygen radical formation during cytochrome P450-catalyzed cyclosporine metabolism
      in rat and human liver microsomes at varying hydrogen ion concentrations.
AB  - The role of pH in uncoupling the electron-flux between oxidoreductase and
      cytochrome P450 (P450) or P450 and cyclosporine (CyA) and resulting in the
      generation of oxygen radicals was investigated in vitro in rat and human liver
      microsomal preparations. Since the electron-flux from NADPH to cytochrome c via
      oxidoreductase showed a fairly constant reduction activity from pH 7.0-9.5, the
      generation of oxygen radicals at the level of P450-Cyclosporine (instead of
      oxidoreductase-P450) was investigated. The effects of increasing pH on oxygen
      radical formation was measured by the thiobarbituric acid assay (TBA) and the
      adrenochrome reaction. The trends in oxygen radical production were correlated
      with benzphetamine metabolism (production of formaldehyde) and CyA metabolism
      (analyzed by high performance liquid chromatography). The TBA assay showed
      increased MDA-detected lipid peroxidation (unrelated to autooxidation) at pH <
      8.0 and pH > 8.0 (rat and human, respectively) while the adrenochrome reaction
      showed decreased oxygen radical production. When these results were compared to
      benzphetamine (a substrate of P450 2B and 3A) metabolism and CyA (a substrate of
      P450 3A) metabolism, increased metabolism followed the pH-dependent trend of MDA
      detected lipid peroxidation. Benzphetamine metabolism with formaldehyde
      production and depletion of parent compound during CyA metabolism were increased
      at pH < 8.0 in the rat samples and at pH > 8.0 in the human samples. This
      parallel relation suggests that the increased metabolism of CyA at lower pH in
      rats and higher pH in humans may be the result of favorable interactions of P450
      with Cyclosporine that also result in increased oxygen radical-related lipid
      peroxidation.

PMID- 8569759
TI  - Binding between lipopolysaccharide and cecropin A.
AB  - Cecropin A (CA), a bioactive peptide, produced significant lethality to Pantoea
      agglomerans (PA) at low concentrations. Significant mortality occurred
      immediately after addition of CA. Separate preincubations of lipopolysaccharides
      (LPS) from the following bacteria: PA, Serratia marcescens, Escherichia coli
      (EC), and Salmonella typhimurium with CA were performed prior to the bioassay. CA
      was also preincubated with diphosphoryl lipid A (DPL-A) from EC and S. minnesota
      (SM), trilinolein, palmitic, lauric and myristic acids (fatty acids contained in
      the lipid A of PA-LPS) and bovine brain gangliosides. Spectral analysis to
      determine the interaction between glycosphingolipids (sphingomyelin, bovine brain
      gangliosides, and galactocerebrosides) and CA were performed. Results showed that
      all types of LPS and DPL-A as well as gangliosides studied blocked CA lethality
      to PA. The level of inhibition of CA antibacterial properties was dependent on
      LPS and DPL-A concentration. The individual fatty acids and trilinolein did not
      affect CA lethality to PA. Spectral studies showed complexation between CA and PA
      LPS, both types of DPL-A, and the glycosphingolipids. Biological and chemical
      analyses confirm that CA binds to the diphosphoryl lipid A moiety of LPS.

PMID- 8569760
TI  - Properties of the sarcoplasmic reticulum Ca(2+)-pump in coronary artery skinned
      smooth muscle.
AB  - Pig coronary artery cultured smooth muscle cells were skinned using saponin. In
      the presence of an ATP-regenerating system and oxalate, the skinned cells showed
      an ATP-dependent azide insensitive Ca(2+)-uptake which increased linearly with
      time for > 1 h. The Ca(2+)-uptake occurred with Km values of 0.20 +/- 0.03 microM
      for Ca2+ and 400 +/- 34 microM for MgATP2-. Thapsigargin and cyclopiazonic acid
      inhibited this uptake with IC50 values of 0.13 +/- 0.02 and 0.56 +/- 0.04 microM,
      respectively. These properties of SR Ca(2+)-pump are similar to those reported
      for membrane fractions isolated from fresh smooth muscle of coronary artery and
      other arteries. However, optimum pH of the uptake in the skinned cells (6.2) was
      lower than that reported previously using isolated membranes (6.4-6.8).

PMID- 8569761
TI  - Genomic cloning and chromosomal assignment of rat regucalcin gene.
AB  - The gene for a Ca(2+)-binding protein regucalcin was cloned from a rat genomic
      library which was constructed in lambda FIX II by screening with radiolabeled
      probe (complementary DNA of rat liver regucalcin). Positive clone had 19.9 kb
      insert of size and contained four exons of the gene coding for a rat regucalcin.
      These exons included the partial coding sequence (61.2% of open reading frame)
      and the entire 3'-untranslated region of the gene. The nucleotide sequence of
      exons completely agreed with that of a rat regucalcin cDNA clone. The sequence
      analysis of the clone showed that the identifier sequence and two simple repeated
      sequences exist in the intron of the gene. Moreover, chromosomal location of the
      rat regucalcin gene was determined by direct R-banding fluorescence in situ
      hybridization (FISH) method with the 19.9 kb clone containing four exons. The
      regucalcin gene was localized on rat chromosome Xq11.1-12 proximal end.

PMID- 8569762
TI  - Troponin subunits contribute to altered myosin ATPase activity in diabetic
      cardiomyopathy.
AB  - Our group has documented that myocardial performance is impaired in the hearts of
      chronically diabetic rats and rabbits. Abnormalities in the contractile proteins
      and regulatory proteins may be responsible for the mechanical defects in the
      streptozotocin (STZ)-diabetic hearts. Previously, the major focus of our research
      on contractile proteins in abnormal states has concentrated on myosin ATPase and
      its isoenzymes. Our present study is based on the overall hypothesis that
      regulatory proteins, in addition to contractile protein, myosin contribute to
      altered cardiac contractile performance in the rat model of diabetic
      cardiomyopathy. The purpose of our research was to define the role of cardiac
      regulatory proteins (troponin-tropomyosin) in the regulation of actomyosin system
      in diabetic cardiomyopathy. For baseline data, myofibrillar ATPase studies were
      conducted in the myofibrils from control and diabetic rats. To focus on the
      regulatory proteins (troponin and tropomyosin), individual proteins of the
      cardiac system were reconstituted under controlled conditions. By this approach,
      myosin plus actin and troponin-tropomyosin from the normal and diabetic animals
      could be studied enzymatically. The proteins were isolated from the cardiac
      muscle of control and STZ-diabetic (4 weeks) rats. Sodium dodecyl sulfate gel
      electrophoretic patterns demonstrate differences in the cardiac TnT and TnI
      regions of diabetic animals suggesting the different amounts of TnT and/or TnI or
      possibly different cardiac isozymes in the regulatory protein complex. Myofibrils
      probed with a monoclonal antibody TnI-1 (specific for adult cardiac TnI) show a
      downregulation of cardiac TnI in diabetics when compared to its controls.
      Enzymatic data confirm a diminished calcium sensitivity in the regulation of the
      cardiac actomyosin system when regulatory protein(s) complex was recombined from
      diabetic hearts. Actomyosin ATPase activity in the hearts of diabetic animals was
      partially reversed when myosin from diabetic rats was regulated with the
      regulatory protein complex isolated from control hearts. To our knowledge, this
      is the first study which demonstrates that the regulatory proteins from normal
      hearts can upregulate cardiac myosin isolated from a pathologic rat model of
      diabetes. This diminished calcium sensitivity along with shifts in cardiac myosin
      heavy chain (V1-->V3) may be partially responsible for the impaired cardiac
      function in the hearts of chronic diabetic rats.

PMID- 8569763
TI  - Lipoprotein receptor 'CK'--dependent signalling in human platelets.
AB  - The study addressed to understand whether or not lipoproteins at low
      concentrations could modulate Receptor-'C' dependent platelet signalling revealed
      that LDL, like exogenous cholesterol, had the capacity to initiate PLD-dependent
      platelet signalling in a dose dependent fashion and this effect was inhibited in
      presence of HDL; cAMP; DTT; Zn++ and butanol whereas cGMP had no effect upon this
      PLD-dependent signalling. Further Receptor 'C' from platelet in the purified-form
      displayed LDL-or cholesterol-dependent autophosphorylation at the tyrosine
      residues and this Receptor-'C' tyrosine kinase (Receptor-Ck) activity contributed
      to the observed LDL-or cholesterol -dependent PLD activity in human platelets.
      Based upon these results coupled with earlier results, an attempt was made to
      define the lipoprotein-dependent platelet signalling pathway.

PMID- 8569764
TI  - Indo-1 can simultaneously detect Ba2+ entry and Ca2+ blockade at a plasma
      membrane calcium channel.
AB  - The fluorescent chelator Indo-1 can make simultaneous determinations of two
      intracellular ion concentrations, such as [Ca2+] and [Cd2+], or [Ca2+] and
      [Ba2+], in a normal cell suspension. The second ion can be detected even if its
      spectrum when bound to Indo-1 is same as for the calcium-bound or the ion-free
      Indo-1, as long as there is a change in height. This is because the mathematical
      analysis uses not only the spectral shape, but also takes into account increases
      in total signal intensity. For maximum accuracy, whole spectra were analyzed.
      When 3 mM [Ba2+] was added to a B cell line that had been stimulated with
      antiimmunoglobulin to open receptor operated calcium channels, there was a sudden
      drop in 400 nm Indo-1 fluorescence. Spectral analysis showed that this was due to
      a drop in intracellular [Ca2+], which was consistent with blockage of the
      receptor-operated calcium current by extracellular Ba2+. The conductance for Ba2+
      was also observable as a slow rise in total fluorescence. There was also a slow
      increase in intracellular [Ca2+] as barium accumulated in the cell, which was
      tentatively attributed to blockage of the plasma membrane calcium pump by
      intracellular Ba2+.

PMID- 8569765
TI  - Energy metabolism response to calcium activation in isolated rat hearts during
      development and regression of T3-induced hypertrophy.
AB  - The effect of calcium activation on energy production was investigated in
      isolated perfused hearts from rats treated with triiodothyronine (T3) during 15
      days (0.2 mg/kg/day) and in hearts of rats allowed to recover after T3-treatment
      during 15 days. Changes in phosphorylated compound concentrations were followed
      in the isolated hearts perfused with a glucose-pyruvate medium by 31P-NMR
      spectroscopy, when the external calcium concentration was increased from 0.5-1,
      1.5 and 2 mM. As expected, T3-treatment resulted in the hypertrophy of the heart
      (50% increase in HW/BW) that was nearly reversible 15 days after discontinuation
      of the treatment. When compared to controls, creatine, phosphocreatine (PCr) and
      glycogen contents were lower (58, 24 and 17% decrease respectively) in the
      hypertrophied hearts and higher (10, 14 and 18% respectively) after regression of
      hypertrophy. Intracellular pH, ATP, inorganic phosphate concentrations and the
      phosphorylation potential were not altered under T3-treatment and after
      regression of hypertrophy, while calculated free ADP concentration was lower in
      hypertrophied hearts (control: 40 +/- 2 microM, T3-treatment: 21 +/- 1 microM,
      regression: 37 +/- 1 microM). Increasing the calcium concentration induced a
      similar increase in left ventricular developed pressure in the three groups of
      hearts, with inorganic phosphate concentration increasing with cardiac work. The
      PCr concentration slightly decreased while the ATP concentration did not change.
      In spite of different initial PCr concentrations, the evolutions of PCr and Pi
      concentrations for each stepwise increase in external calcium were similar in the
      three groups. It is concluded that, in spite of the well-known decrease in
      efficiency induced by the drug, the mechanisms of PCr (ATP) production remain
      able to respond to an acute moderate increase in energy demand provoked by a
      physiological stimulus. This adaptation also persists after the treatment when
      the energy metabolism balance is apparently improved.

PMID- 8569766
TI  - Detection and genotyping of herpes simplex virus types 1 and 2 by polymerase
      chain reaction.
AB  - A simple and rapid polymerase chain reaction (PCR) procedure was developed for
      simultaneous detection and typing of herpes simplex virus (HSV) types 1 and 2. It
      was possible to detect and type HSV using two primers pairs in a simultaneous
      double PCR reaction, where the type of HSV present was determined on the basis of
      an ethidium-bromide-stained band after agarose gel electrophoresis. This PCR
      assay was tested on about 500 clinical specimens.

PMID- 8569767
TI  - A multiplex polymerase chain reaction for distinguishing Mycobacterium
      tuberculosis from Mycobacterium tuberculosis complex.
AB  - A multiplex polymerase chain reaction has been developed which is able to
      distinguish Mycobacterium tuberculosis from other members of the M. tuberculosis
      complex. The assay is based on the simultaneous amplification of two different
      targets: a 396bp region from the mtp40 species-specific gene sequence of M.
      tuberculosis and a 245bp fragment from the M. tuberculosis complex insertion
      sequence IS986. Results have been obtained for 54 mycobacterial strains including
      five non-M. tuberculosis complex isolates. All 49 strains of the M. tuberculosis
      complex were positive for IS986 but only the 27 M. tuberculosis isolates were
      positive for both IS986 and mtp40.

PMID- 8569768
TI  - Molecular typing of Neisseria meningitidis serogroup A using the polymerase chain
      reaction and restriction endonuclease pattern analysis.
AB  - A new molecular typing method for identification and characterization of
      Neisseria meningitidis is reported. Chromosomal DNA from 20 well-documented
      meningococcal strains of serogroup A originating from France, Central African
      Republic, Sudan and Burkina Faso were amplified using the polymerase chain
      reaction. Primers designed in this study were located in the pilA/pilB locus
      which has been shown to be conserved in the genus Neisseria. The amplified
      fragments were subjected to restriction endonuclease analysis using three
      different enzymes, and the restriction endonuclease patterns obtained were
      compared. Clonal isolates clustered together in distinct restriction endonuclease
      patterns which are described in this study and coincided with electrotypes as
      determined by multi-locus enzyme electrophoresis. This DNA-based typing system
      for meningococci may be useful for epidemiological studies.

PMID- 8569769
TI  - Evaluation of a PCR based assay for specific detection of Campylobacter jejuni in
      chicken washes.
AB  - An assay for Campylobacter jejuni based on the polymerase chain reaction was
      developed in our laboratory and shown to be a sensitive and specific method to
      identify this bacterium in pure culture. This assay was evaluated as a method to
      rapidly detect C. jejuni attached to chicken carcasses. Chicken carcasses were
      sampled for PCR using three methods including pre-enrichment of the washes,
      direct plating of the washes and differential centrifugation of the washes prior
      to testing. It was found that plating the wash solutions on Campy Cefex plates
      prior to performing PCR was the most specific and reliable of the three treatment
      methods evaluated.

PMID- 8569770
TI  - Class D and E tetracycline resistance determinants in gram-negative bacteria from
      catfish ponds.
AB  - DNA probes were used to examine tetracycline-resistant Gram-negative bacteria
      (281 strains representing eight species) from catfish ponds. The isolates, which
      did not previously hybridize with the Tet A, B and C determinants, were examined
      for the presence of tetracycline-resistance Tet D and Tet E determinants. The
      distribution of the Tet D determinant ranged from 0 to 83%, depending on the
      bacterial species. Tet E was found only in 69% of Aeromonas hydrophila isolates.
      Eighteen per cent failed to hybridize with any of the five Tet determinants.

PMID- 8569771
TI  - Genetic markers for closely-related parasitic nematodes.
AB  - Seven species of closely-related nematode parasite (Trichostrongylus axei, T.
      colubriformis, T. probolurus, T. retortaeformis, T. rugatus, T. vitrinus and T.
      tenuis) were characterized using a polymerase chain reaction-linked restriction
      fragment length polymorphism technique (PCR-RFLP). The rDNA region spanning the
      first and second internal transcribed spacers as well as the 5.8S rDNA gene
      (ITS+) was amplified from isolates of each of the seven species, digested
      separately with six restriction endonucleases (Dra I, Hinf I, Rsa I, Vsp I, Nla
      III and Tsp 509 I) and the fragments separated by agarose gel electrophoresis.
      PCR-RFLP of ITS+ produced characteristic patterns for each Trichostrongylus
      species examined. No variation in RFLP patterns was observed among different
      isolates for species where multiple isolates were examined. The present study
      demonstrates that the ITS+ provides genetic markers for the species
      identification of closely-related parasitic nematodes, and indicates the
      usefulness of these markers for diagnostic purposes, and epidemiologic and
      molecular-systematic studies on parasites and other eukaryotic organisms.

PMID- 8569772
TI  - Identification of Mycobacterium tuberculosis complex, Mycobacterium avium and
      Mycobacterium intracellulare by selective nested polymerase chain reaction.
AB  - A nested polymerase chain reaction (PCR) procedure was devised for identification
      of mycobacteria. The outer reaction exploiting genus-specific sequences on the
      16S rRNA gene was able to amplify specifically strains of the genus
      Mycobacterium. The identification of Mycobacterium tuberculosis complex,
      Mycobacterium avium and Mycobacterium intracellulare was accomplished by
      selective reamplification of the outer PCR product in three distinct inner
      amplifications exploiting species-specific primers mapping to a hypervariable
      region of mycobacterial 16S rRNA. Detection of mycobacteria, other than those for
      which species-specific primers were used, was accomplished by adding a
      supplementary genus-specific upper primer to one of the inner reactions.
      Specificity of amplification was confirmed for clinical isolates and reference
      strains of different mycobacterial species with the exception of a M.
      intracellulare type 7 strain which was recognized as M. avium. The amplification
      protocol presented thus provides a reliable and cost-effective way for
      identification of clinically relevant mycobacteria.

PMID- 8569773
TI  - Detection of two groups of 25.2 MDa Tet M plasmids by polymerase chain reaction
      of the downstream region.
AB  - Forty-four Neisseria gonorrhoeae, 12 N. meningitidis, four Kingella denitrificans
      and one Eikenella corrodens carrying 25.2 MDa Tet M plasmids were analysed using
      polymerase chain reaction (PCR) to the downstream region of the incomplete Tet M
      transposon. From each isolate, one of two different PCR fragments of
      approximately 700 or 1600 bp were obtained. The two different sized PCR fragments
      had > or = 90% DNA sequence identity with Ureaplasma urealyticum Tet M downstream
      sequences. The difference between the large PCR fragment and the smaller PCR
      fragment was a deletion of over 800 bp in the smaller fragment. Both PCR
      fragments were found in plasmids isolated from N. gonorrhoeae and K.
      denitrificans. The smaller PCR fragment was found in N. meningitidis plasmids and
      the larger PCR fragment was found in the E. corrodens plasmid.

PMID- 8569774
TI  - Variable efficiency of three primer pairs for the diagnosis of Pneumocystis
      carinii pneumonia by the polymerase chain reaction.
AB  - The efficiency of three different primer pairs, complementary to different
      Pneumocystis carinii DNA regions, was compared in the polymerase chain reaction
      (PCR) for the diagnosis of Pneumocystis carinii pneumonia (PCP) on
      bronchoalveolar fluid (BALF) from patients with AIDS. PCR coupled with dot-blot
      hybridization (BLOT) using primers and probe from the mitochondrial 23SrDNA
      region showed the highest sensitivity, with a lower detection limit of 0.5-1
      organisms microliter-1. When testing 47 BALF, PCR plus BLOT of the mitochondrial
      23SrDNA region showed also the best diagnostic efficiency (97% sensitivity, 100%
      specificity). Sensitivity was significantly higher than with PCR and BLOT of the
      5SrDNA region (81.5% sensitivity; P = 0.025, McNemar test); and of the
      dehydrofolate reductase (DHFR) gene region (75.6% sensitivity; P = 0.019).
      Sensitivity was also significantly higher than indirect immunofluorescence (75.8%
      sensitivity; P = 0.008). Using DHFR primers and probe, specificity was also
      reduced. The diagnostic sensitivity in clinical specimens paralleled the
      detection limit in the standard dilutions. The use of repeated DNA sequences of
      proven specificity as target of PCR amplification favourably influences
      sensitivity and specificity. This comparative study demonstrates that primer
      selection plays a significant role in the diagnosis of PCP by PCR.

PMID- 8569776
TI  - Internal controls as performance monitors and quantitative standards in the
      detection by polymerase chain reaction of herpes simplex virus and
      cytomegalovirus in clinical specimens.
AB  - Internal controls (IC) were produced and characterized for an HSV and a CMV PCR
      assay which serve both as test performance monitors and as quantitative
      standards. In each of the PCR assays the IC and native targets were amplified
      with equal efficiency and were detected with the same sensitivity, i.e. < 10
      target copies. An algorithm was developed for the use of IC as a quantitative
      standard which entailed coamplifying a test specimen with four two-fold dilutions
      of the respective IC target (63-500 copies), followed by regression analysis of
      the relative yield of amplification products. This approach allowed the
      determination of both the initial virus genome copy number and the variability of
      the results, which provided a confidence index for the PCR assay. The relative
      yields of PCR products were determined by Southern blot and probe hybridization
      and by densitometry of digitized ethidium bromide-stained gels. Both methods
      produced estimations of the initial target copy numbers within +/- 40% of the
      expected value. Such a comprehensive analysis of an internal control for a PCR
      assay provides a rigorous control of test performance and permits reliable
      quantitative interpretation of a PCR assay result.

PMID- 8569775
TI  - Evaluation of the effects of disinfectants on rotavirus RNA and infectivity by
      the polymerase chain reaction and cell-culture methods.
AB  - Rotaviruses have been linked to outbreaks of acute gastroenteritis of children in
      day-care centres and hospital paediatric wards. There is, therefore, the need for
      monitoring effective decontamination of such environments. We have evaluated the
      effects of seven different methods of disinfection/inactivation (four chemical
      and three physical) on rotavirus using the PCR and cell-culture methods. We
      observed that 6% H2O2, 2500 ppm chlorine, an ethano-phenolic disinfectant, u.v.
      irradiation and heat completely destroyed the infectivity of rotavirus as well as
      RNA amplifiable by PCR. On the other hand, treatment with 80% ethanol resulted in
      the loss of infectivity despite the fact that RNA was still amplifiable.
      Rotavirus subjected to drying over a 24 h period still retained amplifiable RNA
      but infectivity was reduced by 100-fold when compared to the control. This study
      demonstrated an agreement between PCR and cell-culture monitoring systems,
      however, PCR is a more rapid and sensitive assay.

PMID- 8569777
TI  - Simultaneous detection of fourteen Italian cystic fibrosis mutations in seven
      exons by reverse dot-blot analysis.
AB  - The increasing number of cystic fibrosis (CF) mutations is a great obstacle to
      the use of DNA procedures in the detection of gene defects. We describe a fast,
      cheap and non-radioactive procedure, Reverse dot-blot analysis (RDB), for the
      simultaneous detection of CF mutations in the Italian population. We used this
      approach to study seven exons of the CF gene for 14 CF gene defects and were able
      to characterize 222 of 272 CF chromosomes (80%). The cost of the procedure was
      $25 per sample analysed.

PMID- 8569778
TI  - Molecular characterization of further dystrophin gene microsatellites.
AB  - Microsatellites of the dystrophin gene have been used extensively in the genetic
      analysis of Duchenne and Becker muscular dystrophy families. The microsatellites
      that have been reported to date are clustered within disparate regions of the
      dystrophin gene, specifically at the 5'-end and in the central rod-domain. YACs
      encompassing the gene were screened for further microsatellites to improve the
      density of available genetic markers. Four microsatellites were localized to
      defined regions of the dystrophin gene by the analysis of patient DNA samples,
      somatic cell hybrids and YACs. In addition, varying combinations of
      microsatellite loci were amplified in multiplex PCRs, which complement those loci
      that have been studied to date.

PMID- 8569779
TI  - Two restriction fragment length polymorphisms at the apolipoprotein AIV (apoAIV)
      locus.

PMID- 8569780
TI  - Design and evaluation of new, highly sensitive and specific primers for
      polymerase chain reaction detection of HIV-1 infected primary lymphocytes.

PMID- 8569781
TI  - Mutation spectra of chemical fractions of a complex mixture: role of nitroarenes
      in the mutagenic specificity of municipal waste incinerator emissions.
AB  - Using an ion-exchange procedure coupled to a microsuspension Salmonella assay, we
      fractionated the dichloromethane-extractable particulate organics emitted by a
      municipal waste incinerator. Most (80-95%) of the mutagenic activity resided in
      the neutral/base fraction; however, the polar neutral fraction accounted for 12%
      of the direct-acting mutagenic activity. The mutagenic potencies of the whole
      extract and the various fractions were 4-15 times greater in the absence than in
      the presence of S9. Results with strains deficient in classical nitroreductase
      (TA98NR) and transacetylase (TA98/1,8-DNP6) indicated that a majority of the
      direct-acting mutagenicity was due to nitroarenes. This was confirmed by bioassay
      directed subfractionation of the neutral/base faction by a cyanopropyl/HPLC
      method. The mutations in -3,000 revertants (approximately 400 each induced in
      TA98 by the whole extract, the neutral/base and polar neutral fractions from the
      ion-exchange column and 3 of the neural/base subfractions from the HPLC column;
      along with 200 revertants each induced by the model nitroarene 1-nitropyrene
      (1NP) in strains TA98, TA1538 and TA100) were analyzed by probe hybridization and
      PCR/DNA sequence analysis. The results indicated that nitroarenes such as 1NP
      that eluted in the neutral/base fraction accounted for at least 50% of the direct
      acting mutagenicity and induced only a hotspot 2-base deletion in the sequence
      (CG)4 in TA98. In contrast, most of the complex frameshifts (a frameshift with a
      flanking base substitution) induced by the whole extract were induced by
      nitroarenes other than 1NP that were activated by transacetylation and that
      eluted in the polar neutral fraction. This study (1) identifies nitroarenes as an
      important contributor to the mutagenic activity of the emissions from municipal
      waste incinerators; (2) confirms our previous conclusion that the mutation
      spectrum of a complex mixture reflects the dominance of particular classes of
      chemical mutagens within the mixture; and (3) demonstrates the possibility of
      isolating certain chemical fractions of a complex mixture that induce certain
      classes of mutations produced by the whole, unfractionated mixture.

PMID- 8569782
TI  - Increase in hypoxanthine-guanine phosphoribosyl transferase gene mutations by
      exposure to high-density 50-Hz magnetic fields.
AB  - Exposure to extremely low frequency magnetic field (ELFMF) of 50 Hz and 400 mT
      induced mutations in the hypoxanthine-guanine phosphoribosyl transferase gene of
      human melanoma MeWo cells. The mutant frequency was enhanced both by increasing
      the exposure period and the induced current intensity. Mutations induced by X
      rays were enhanced by ELFMF exposure. No significant increase in mutant frequency
      occurred when DNA replication was inhibited during ELFMF exposure. DNA
      replication error is suspected of causing the mutations produced by ELFMF
      exposure.

PMID- 8569783
TI  - Levels of ras oncoproteins in human plasma from 1,3-butadiene-exposed workers and
      controls.
AB  - In a Czech plant near Prague, 10 samples from male workers occupationally exposed
      to 1,3-butadiene and 13 exposed to 1,3-butadiene/styrene were compared with
      unexposed male negative controls, matched for age and smoking habits, for the
      presence of ras oncoproteins in their plasma. Proteins were separated by gel
      electrophoresis, transferred to a nitrocellulose membrane by Western blotting and
      detected by chemiluminescence, using monoclonal ras antibody as the primary
      antibody. There were no statistically significant differences between the 3
      groups (pooled two-sample t-test, untransformed and non-parametric Mann-Whitney
      test). These results are in keeping with the lack of exposure-related effects for
      3 cytogenetic endpoints (chromosome aberrations, sister chromatid exchanges and
      micronuclei) already reported (Sorsa et al., 1994 Mutation Res., 309, 321-326)
      for this work-force exposed to low (below 3 ppm) exposure levels.

PMID- 8569784
TI  - ras oncoproteins in human plasma from lung cancer patients and healthy controls.
AB  - In order to explore the significance of ras oncoproteins in plasma in the
      carcinogenic process, we have examined samples from 40 Polish human lung cancer
      patients prior to treatment. They were compared with 35 healthy donors and have
      been screened using a direct analysis of the plasma. Proteins were separated by
      gel electrophoresis, transferred to a nitrocellulose membrane by Western blotting
      and detected by chemiluminescence, using monoclonal ras antibody as the primary
      antibody. Elevated increases in ras oncoproteins were determined where an
      increase was considered to be greater than 2 standard deviations above the mean
      negative control values. The results showed that in 45% of cancer patients ras
      oncoprotein levels were statistically significantly increased (P < 0.001, pooled
      two-sample t-test untransformed, and non-parametric Mann-Whitney test) in the
      plasma by comparison with 6% in the controls. This would suggest that an increase
      in ras oncoproteins in plasma could be a possible prognostic marker or biomarker
      for lung cancer.

PMID- 8569785
TI  - Detection of chromosomal aberrations by fluorescence in situ hybridization in the
      first three postirradiation divisions of human lymphocytes.
AB  - Chromosomal aberrations in human lymphocytes were analyzed by fluorescence in
      situ hybridization (FISH) in the first 3 postirradiation (0 and 2 Gy) divisions.
      Cells were grown in the presence of BrdU, collected at different sampling times
      (47, 70 and 91 h) and analyzed using an alphoid centromeric probe and PCR
      amplified DNA libraries for chromosomes 2 and 8. Following differential staining
      of sister chromatids, the analyzed cells were identified to be either in the
      first, second or third mitosis after irradiation. The frequencies of both
      dicentrics and fragments showed a reduction of about 50% after each cell
      generation, whereas translocations were more persistent. Cells within the same
      postirradiation division showed higher aberration frequencies when derived from
      later sampling times, indicating a delay in progression of aberrant cells. As a
      result, the frequencies for dicentrics and fragments remained rather constant at
      different sampling times if the cell cycle parameter was not taken into account.
      Thus, the average generation time of the lymphocytes had a clear effect on the
      obtained aberration frequencies. The described method allows the study of the
      persistence of chromosome damage using the FISH technique during 3 subsequent
      cell divisions in vitro.

PMID- 8569786
TI  - Mutagenicity of nitrophenanthrene derivatives for Salmonella typhimurium: effects
      of nitroreductase and acetyltransferase.
AB  - To determine the mutagenicity of nitrophenanthrenes, three mononitrophenanthrenes
      (NPhs), 11 dinitrophenanthrenes (diNPhs) and eight trinitrophenanthrenes (tiNPhs)
      were synthesized, and their mutagenicity was investigated by using Salmonella
      typhimurium his- strains TA98, TA100, and TA98NR, nitroreductase-deficient, and
      TA98/1,8-DNP6, O-acetyltransferase-deficient mutants, and strains YG1021 and
      YG1026, nitroreductase-overproducing mutants of TA98 and TA100, respectively, and
      strains YG1024 and YG1029, O-acetyltransferase-overproducing mutants of TA98 and
      TA100, respectively. 1-, 3- and 9-NPhis induced 329, 620 and 438 revertants per
      nmol in strain TA100, respectively, and 4,839, 11,309 and 16728 revertants per
      nmol, respectively, in strain YG1029. Mutagenicity of 1,6-, 2,6-, 2,9-, 2,10-,
      3,5-, 3,6- and 3,10-diNPh was elevated in strains YG1021, YG1024, YG1026 and
      YG1029. Among these derivatives, 1,6-, 2,6-, 3,6- and 3,10-diNPhs were more
      mutagenic in strains YG1024 and YG1029 than YG1021 and YG1026, and they showed a
      structure-activity relationship between mutagenicity and NO2-substitution. Nitro
      derivatives substituted at the 3 and 6 positions of their chemical structure
      strongly mutated both strains YG1024 and YG1029, whereas those substituted at the
      9 and 10 positions showed weak mutagenicity. In addition, nitro substituents at
      positions 4 and 5 were perpendicular while those on positions 2,3,6 and 7 were
      nearly coplanar to the aromatic ring. Furthermore, 2,6,9-, 3,6,9- and 1,6,9
      trinitrophenanthrenes (triNPhs) were mutagenic for strain TA100, and their
      mutagenicity was more enhanced in YG1024 and YG1029 than in YG1021 and YG1026. Of
      the eight triNPhs all except 1,5,10-triNP were mutagenic in TA98 and TA100, and
      their mutagenicity was more enhanced in YG1024 and YG1029 than in YG1021 and
      YG1026. These results suggest that these compounds are mutagens that are
      activated by O-acetyltransferase esterification following nitroreductase. The
      nitrated derivatives substituted at the 2(7) and 3(6) positions of the
      phenanthrene ring were highly mutagenic. The relationship between chemical
      structure and the mutagenicity of NPh derivatives is discussed.

PMID- 8569787
TI  - Cytogenetic and genetic studies of radiation-induced chromosome damage in mouse
      oocytes. I. Numerical and structural chromosome anomalies in metaphase II
      oocytes, pre- and post-implantation embryos.
AB  - The incidences of X-ray induced numerical and structural chromosome anomalies
      were screened in a range of developmental stages from metaphase II oocytes
      through to post-implantation embryos. Following 1 Gy of acute X-rays to
      immediately preovulatory stage oocytes, the rate of hyperploidy (chromosome gain)
      was found to be elevated over levels in unirradiated controls, at metaphase II,
      in 1-cell and 3.5 day pre-implantation embryos but not in 8.5 day post
      implantation foetuses. In the latter, however, the frequency of mosiacism was
      significantly increased. A similar response of an increase in mosaicism but not
      in hyperploidy in 8.5 day post-implantation embryos was also found after
      irradiation of dictyate stage oocytes with 4 Gy of acute X-rays. Significantly
      elevated frequencies of structural chromosome anomalies were present in metaphase
      II oocytes and pre-implantation embryonic stages, but could not be detected in
      block-stained chromosome preparations from 8.5 day post-implantation foetuses.
      However, analysis of chromosome preparations after G-banding showed that almost
      14% of 14.5 day foetuses carried a chromosome rearrangement after 1 Gy of X-rays
      to immediately preovulatory stage oocytes. Overall, our data indicate that the
      presence of radiation-induced chromosome gains are incompatible with embryonic
      survival but that a proportion of embryos with structural chromosome damage
      develop past mid-gestation. These latter embryos are therefore potentially
      capable of contributing to the genetic burden of the next generation.

PMID- 8569788
TI  - Cytogenetic and genetic studies of radiation-induced chromosome damage in mouse
      oocytes. II. Induced chromosome loss and dominant visible mutations.
AB  - The rates of X-ray induced loss of chromosome 19 in mouse oocytes were
      investigated in 2 experiments using a genetic complementation test. After 1 Gy of
      acute X-rays to immediately preovulatory stage oocytes, chromosome 19 loss was
      estimated to have occurred in 1.68% of cells. In comparison, after 4 Gy of acute
      X-rays to dictyate stage oocytes, the rate was estimated at 1.18%. The slightly
      higher rate of chromosome loss in the former cell stage after a smaller dose of
      radiation reflects the known increased radiosensitivity of mouse oocytes in the
      period shortly before ovulation. Comparison of the observations here for
      chromosome 19 with published data for chromosome 1 suggests that chromosome
      length is one of the principal factors in determining the initial rate of induced
      loss in mouse oocytes. Ten dominant visible mutations were recovered among 1674
      offspring following irradiation of preovulatory oocytes, and 8 in 2025 offspring
      after treatment of dictyate cells. Nine dominant mutations were karyotyped, 5 of
      these were found to be associated with a visible chromosome rearrangement. The
      data obtained in the present study show that radiation-induced chromosome
      anomalies in female germ cells are not all filtered out by prenatal embryonic
      death but that a proportion has the potential to contribute to the genetic burden
      of the next generation.

PMID- 8569789
TI  - Deletion during recombination in bacteriophage T7.
AB  - The ligase gene of bacteriophage T7 was interrupted with inserts made from
      synthetic DNA. A pair of inserts were designed so that each insert contained one
      copy of an identical 17 bp sequence (repeat) positioned such that intermolecular
      recombination between the 17 bp homologies on separate genomes could delete
      enough of the insert to produce a functional ligase gene. The frequency of
      deletion by intermolecular recombination was compared to deletion frequency when
      repeated copies of the identical 17 bp sequence were present on the same genome
      separated by 39 bp. When the 17 bp homologous sequences were on different genomes
      the formation of ligase positive phage was about 7% to 13% of the deletion
      frequency measured with both repeats on the same genome. A second set of inserts
      contained the same 17 bp sequence present in the first pair of inserts. The
      sequence of this second set of inserts was such that when both 17 bp repeats were
      present on the same genome there was no separation between the repeats. With the
      second set of inserts (no separation) deletion by intermolecular recombination
      was about two orders of magnitude higher than what was measured with the first
      set of inserts where 39 bp of nonhomologous sequence intervened between the 17 bp
      repeats and the normal T7 genome. These data are interpreted to suggest that in
      T7 misalignment between repeated sequences during intermolecular recombination
      may play a role in deletion mutagenesis.

PMID- 8569790
TI  - Mutation induction in gamma-irradiated primary human bronchial epithelial cells
      and molecular analysis of the HPRT- mutants.
AB  - We have examined various radiobiological parameters using commercially-available
      primary normal human bronchial epithelial (NHBE) cells, which can be subcultured
      more than 20 population doublings, and have established the mutation system in
      order to characterize the molecular changes in gamma-irradiated primary cells.
      The survival curve, obtained after irradiation of cells with 137Cs gamma-rays,
      indicates that the D0, Dq, and n values are 1.34 Gy, 1.12 Gy, and 2.3,
      respectively. The induction of HPRT- mutation was dose-dependent and the mutant
      fraction increased in a non-linear fashion. Since the doubling number of NHBE
      cells is limited, DNA was extracted directly from the single mutant colonies and
      alteration in the HPRT gene locus was analyzed using multiplex PCR technique.
      Among spontaneous mutants, the proportion with total and partial deletions of the
      gene was 10.0% (2/20) and 60.0% (12/20), respectively, while 30.0% (6/20) did not
      have any detectable changes in the nine exons examined. On the other hand, the
      fraction of total deletion increased by more than 2-fold among mutants induced by
      gamma-rays in that 26.3% (10/38) of them showed the total gene deletions. Twenty
      five out of 38 gamma-induced mutants (65.8%) had partial deletions and 3 mutants
      (7.9%) had no detectable alteration. The present results showed that gamma
      irradiation efficiently induced HPRT gene mutation in primary human epithelial
      cells and that most of the induced mutants suffered larger deletions compared to
      that observed in spontaneous mutants. This system provides an useful tool for
      determination of mutagenicity and understanding the molecular mechanisms of
      environmental carcinogens in primary human bronchial cells.

PMID- 8569791
TI  - Increased micronucleus frequency in lymphocytes from smokers with lung cancer.
AB  - We investigated whether lung cancer was associated with an increased micronucleus
      (MN) frequency in lymphocytes in a case-control study. Epidemiological data were
      obtained by an interviewer-administered questionnaire and included information on
      smoking history, intake of dietary micronutrients, general medical history,
      environmental and occupational exposures to mutagens and carcinogens, and family
      history of cancer. A modified cytokinesis-block method was used to determine
      individual MN frequency. Polymorphisms in glutathione S-transferase class mu were
      determined by PCR analysis. Overall, 55 controls and 42 cases were studied. MN
      frequency in cases and controls was not associated with age, smoking, metabolic
      genetic polymorphisms, environmental and occupational exposures, or medical
      history. Female controls had a significantly higher MN frequency than male
      controls (p = 0.05). Overall, MN frequency was significantly higher in cases than
      in controls (p < 0.01). Twenty-four cases (57%) had an MN frequency higher than
      the upper 95% confidence interval of the mean value for controls (11.5 MNs/1000
      binucleated cells). Further analysis showed that, cases who were current and
      former smokers had significantly higher MN frequencies than controls (p = 0.04);
      this difference was not seen in the group that had never smoked. The
      significantly higher MN frequency among cases with a history of smoking may be
      attributable to the presence of lung neoplasm per se or to the interaction of
      smoking with endogenous factors associated with the development of lung cancer.

PMID- 8569792
TI  - Peroxynitrite-induced mutation spectra of pSP189 following replication in
      bacteria and in human cells.
AB  - Peroxynitrite is a powerful oxidant formed through reaction of nitric oxide with
      superoxide. Because activated macrophages can produce both nitric oxide and
      superoxide, it has been proposed that peroxynitrite may contribute to
      cytotoxicity and increased cancer risks associated with the inflammatory response
      during chronic infections. We therefore investigated mutagenicity of
      peroxynitrite in the supF gene of the pSP189 shuttle vector as a mutation target.
      The plasmid was exposed to 2.5 mM peroxynitrite in vitro, then replicated in
      Eschericia coli MBL50 and in human AD293 cells. Mutation frequency increased 21
      fold in pSP189 replicated in E. coli and 9-fold in plasmid replicated in human
      cells. Mutations were clustered within the 5' region of the supF gene in plasmids
      replicated in bacteria. The hot spots were located at positions 108, 113, 116,
      124, 126 and 141; more than 25% of all mutations occurred at position 124.
      Following replication in human cells, mutations were more widely distributed over
      the gene, with hot spots at positions 113, 124, 133, 156 and 164; 15% occurred at
      position 124. In both systems, the majority of mutations occurred at G:C base
      pairs, predominantly involving G:C-->T:A transversions (65% when replication was
      in bacteria and 63% when in human cells). G:C-->C:G transversions were observed
      at lower frequency (28% in MBL50 and 11% in AD293 cells), and 11% of mutations
      found in vectors replicated in AD293 cells were G:C-->A:T transitions. A greater
      number of large deletions, insertions, tandem and multiple mutations occurred in
      plasmid replicated in AD293 cells. Differences in mutation spectra following
      replication in the two systems may be attributable to differences in recognition
      and repair of the lesions and/or properties of the replication apparatus.

PMID- 8569793
TI  - Reversion in Chinese hamster lines amplified at the AMPD2 locus: spontaneous and
      benzamide-stimulated gradual loss of amplified alleles of marker genes.
AB  - The HC47 and HC474 cell lines of Chinese hamster fibroblasts resist coformycin
      through the intrachromosomal amplification of the AMP deaminase 2 (AMPD2) gene.
      Due to the coamplification of a mu glutathione S-transferase (GST) gene, these
      mutant lines are more sensitive than GMA32 wild-type parental cells to buthionine
      sulfoximine (BSO), an inhibitor of glutathione biosynthesis. This property was
      exploited to select revertants of amplification from HC474 cells. Reversion in
      that line is frequently a gradual process that does not involve extrachromosomal
      intermediates. The terminal products of this process are commonly cells with a
      complete deletion of the amplified allele of marker genes and are therefore
      haploid for these loci on the homologous chromosome. Exposing HC474 cells to
      benzamide (BA), an inhibitor of polyADP-ribosylation, increased the recovery of
      revertants to an extent allowing the detection of reverting cells without BSO
      selection. This effect of BA was used to isolate revertant cells from the HC47
      line that is extremely stable and to demonstrate that the mechanism of gradual
      reversion also occurs in this line. The gradual deletion of amplified copies
      within the chromosomes suggests that breakage-fusion-bridge (BFB) cycles drive
      this process.

PMID- 8569795
TI  - A study of the structural basis of the carcinogenicity of tamoxifen, toremifene
      and their metabolites.
AB  - An analysis of the chemical structure of tamoxifen, toremifene and their
      metabolites indicates that metabolism to a DNA-reactive hydroxylamine
      intermediate is possible. The parent compounds and many of their metabolites are
      predicted to be rodent carcinogens. Moreover, many of these metabolites contain a
      6 A or 8.4 A distance descriptor biphore. These geometric descriptors may be
      related to an ability of these chemicals to bind to an estrogen receptor. The
      prediction of the carcinogenicity of toremifene is not in accord with studies
      published thus far. However, the reports available have not excluded this
      possibility, since the protocols used have not addressed it systematically.

PMID- 8569794
TI  - Comparative analysis of colchicine induced micronuclei in different cell types in
      vitro.
AB  - In the present study we analyzed the induction of micronuclei (MN) by colchicine,
      at different treatment times, in four histogenetically different cell cultures:
      human skin fibroblasts (HSF), bovine skin fibroblasts (BSF), bovine bladder
      fibroblasts (BBF) and human skin epithelial cells (HK), developed and
      characterized in our laboratory. The frequencies of dead cells, nuclear budding
      and mitotic index were also evaluated. The HSF and BSF cell lines showed similar
      frequencies of micronucleated cells (4.7% and 4.9%, respectively) at 96 h of
      treatment time. The BBF cell line showed the lowest frequency of micronucleated
      cells (2.6%) and HK did not show any MN. The studied cell lines differed in their
      responses to colchicine. The data revealed the relevance of utilization of other
      end-points as growth curves, dead cells, mitotic index and other nuclear
      alterations for accurate analysis of the effect of agents that disturb cell cycle
      or are cytotoxic.

PMID- 8569796
TI  - Multiple, large deletions in rat mitochondrial DNA: evidence for a major hot
      spot.
AB  - This study identified 33 different deletions in mitochondrial DNA from four aging
      Fischer-344 rat brains and from a cultured rat lymphoma cell line (Nb2 cells).
      The deletions were located in the longer arc between the heavy and light strand
      origins of replication. PCR products that spanned across the deleted regions were
      sequenced, and deletions ranging between 6548 bp and 9977 bp in length were
      identified. Short direct repeats of < or = 8 bp were present at the end points of
      all but one of the deletions. The remaining deletion contained, instead, a near
      perfect direct repeat (9/10 bp) within two base pairs of its end points. In 24 of
      the deletions, a sequence equivalent to one member of the paired direct repeats
      was lost with the deleted segment. In the remaining nine, either more or less of
      the base pairs of a single repeat were lost. Twelve of the 33 different deletions
      terminated on one side at a common locus (major hot spot) of 5 bp in length,
      located at the 5' end of the tRNAThr gene. The opposite ends of these 12
      deletions were at different sites. The hot spot was located in a region of the
      mtDNA with strong potential for secondary structure and was flanked by a pair of
      AT-rich sequences. The utilization of the hot spot as an end point for deletions
      appeared to be widespread in that it was represented in 1/3-1/2 of the deletions
      characterized in each of the five mtDNA sources examined. In addition, several
      minor hot spots, where one end of two or three different deletions coincided,
      were also identified.

PMID- 8569797
TI  - Vicia faba root tip micronucleus test on the mutagenicity of water-soluble
      contents of cigarette smoke.
AB  - The possible mutagenicity of the water-soluble contents of cigarette smoke (WSCS)
      was evaluated by using the Vicia faba root tip micronucleus test. The results
      showed significant changes in micronucleus frequency which were caused by each
      different concentration of WSCS. This indicates that the Vicia faba root tip
      micronucleus test might be used as one kind of mutagenic detection method for
      cigarette smoke. A comparative evaluation on the mutagenicity of 10 brands of
      cigarettes was carried out. Results confirmed that various degrees of
      mutagenicity were found for all of the brand cigarettes, among them, Huaihai was
      the highest, while Camellia was the lowest. The micronucleus frequencies were
      reduced by adding tea polyphenol, nicotinamide adenine, vitamin C and sodium
      selenite to the WSCS. The results suggest that these added substances might
      reduce the genetic injury induced by cigarette smoke.

PMID- 8569798
TI  - DNA strand break by 2,5-dimethyl-4-hydroxy-3(2H)-furanone, a fragrant compound in
      various foodstuffs.
AB  - 2,5-Dimethyl-4-hydroxy-3(2 H)-furanone (DMHF), produced by Maillard reaction of
      sugar/amino acid and found in various foodstuffs, showed mutagenicity to
      Salmonella typhimurium TA100 strain with and without S9 mix, and induced
      micronucleated mouse peripheral reticulocytes. DNA strand breaking activity of
      the compound at pH 7.4 increased with the increasing dose of the compound and
      with the increasing incubation time. The breaking activity was inhibited in the
      presence of superoxide dismutase, catalase, hydroxyl radical scavengers, spin
      trapping agents, thiol compounds and metal chelators, and also by removal of
      dissolved oxygen from the incubation mixture. Addition of Fe(III) ion to the
      incubation mixture enhanced the breaking activity. Incubation of DMHF with 5,5
      dimethyl-1-pyrroline N-oxide (DMPO) gave electron spin resonance signals
      characteristic to DMPO-OH adduct, indicating generation of hydroxyl radical. It
      was found that DMHF generated hydroxyl radical with an aid of a trace amount of
      metal ions, and induced DNA strand breaking. Mutagenicity and induction of
      micronucleated reticulocytes by DMHF may be caused as a result of DNA
      modification via hydroxyl radical.

PMID- 8569799
TI  - Effect of sulphur dioxide exposure on human chromosomes.
AB  - The genotoxic effects of an average concentration of 41.7 mg/m3 of SO2 exposure
      on 42 workers of a fertilizer factory were investigated. Mitotic index (MI),
      chromosomal aberrations (CAs), sister-chromatid exchanges (SCEs) and satellite
      associations (SA) were observed. In SO2-exposed workers, a higher mitotic index
      (7.09) was recorded in comparison to controls (4.34). The MI, however, declined
      with duration of exposure. Satellite associations showed a two-fold increase
      (17.1) as compared to controls (8.11). Among chromosomes, D-G group associations
      were the highest (7.43%), while 3D type associations were the lowest (0.4%).
      There was a significant difference (p < 0.05) in the mean frequency of CAs per
      cell in the exposed workers (3.262%) and the controls (0.833%). The mean
      frequency of SCEs per cell increased from 3.32 +/- 0.1 in controls to 7.72 +/-
      0.19 in the exposed group. The difference was significant (p < 0.05). In smokers,
      alcoholics and smoker-alcoholics, the frequency of CAs and SCEs per cell was
      significantly higher than the non-smokers and non-alcoholics, both in the
      controls and the SO2-exposed workers and showed a correlation with the duration
      of exposure. SO2 is therefore a clastogenic and genotoxic agent for which
      necessary precautions must be taken.

PMID- 8569800
TI  - Enhancement of chromosome aberrations by the combination of DNA substitution with
      halogenated deoxyuridine and streptonigrin treatments.
AB  - We treated CHO cells with streptonigrin (SN) alone, in combination with BrdUrd or
      IdUrd substitution, and with or without the addition of caffeine. The cells
      assessed for chromosome damage by SN were in the G2 period and the magnitude of
      the damage was expressed as monosubstituted chromatid breaks, bisubstituted
      chromatid breaks and boundary regions breaks (boundary regions indicate the point
      of exchange of mono- and bisubstituted chromatids). We found that the combination
      of BrdUrd or IdUrd substitution with SN treatments produced a remarkable increase
      in the frequency of breaks over the frequencies observed with the halogenated
      compound only. The effect was more evident with IdUrd than with BrdUrd, and more
      dramatic in bisubstituted than in monosubstituted chromatids. The frequency of
      boundary breaks in cells treated with BrdUrd plus SN was similar to the frequency
      of breaks in monosubstituted chromatids treated similarly. Conversely, the damage
      in boundary regions was almost similar to that in bisubstituted chromatids in
      cells challenged with IdUrd plus SN. The addition of caffeine to BrdUrd
      substituted chromosomes gave rise to a marked enhancement of breakages with a
      gradient of chromatid damage that was: bisubstituted > monosubstituted > boundary
      regions. A further increase of chromatin breaks maintaining the gradient
      indicated above was obtained when the cells were treated with BrdUrd plus SN plus
      caffeine. We propose that BrdUrd and IdUrd substitution alone or in combination
      with caffeine treatments and with SN in its capacity to bind DNA, give rise to
      different chromatin structures capable of modulating the DNA damage induced along
      the chromatin fibril by the active oxygen species liberated by SN-DNA complexes.

PMID- 8569801
TI  - In situ monitoring with the Tradescantia bioassays on the genotoxicity of gaseous
      emissions from a closed landfill site and an incinerator.
AB  - A dual monitoring system composed of the Tradescantia-Micronucleus (Trad-MCN) and
      Tradescantia-Stamen-Hair-Mutation (Trad-SHM) bioassays was utilized to monitor
      directly the genotoxicity of the gaseous emission at a closed landfill site and
      around an incinerator. Four of the commonly emitted gaseous agents from the
      landfill flare pipes, i.e. toluene, ethylbenzene, trichloroethylene and
      ethyltoluene were also evaluated for their genotoxicity in the laboratory. The in
      situ monitoring trips (360 km one way) were carried out by transporting the plant
      cuttings in a clean air box or in an air-tight plastic bag to the site and
      exposing these test cuttings for 5-7 h. The exposed plant samples were examined
      for micronuclei frequencies or the pink mutation rate after the appropriate
      recovery periods (24 h for MCN, 7-11 days for SHM). A total of 20 monitoring
      trips were made to the landfill, and 8 to the nearby surroundings (100-500 m from
      the chimney) of the incinerator site in a two year period. The major findings of
      the Trad-MCN test on the clastogenicity of the gaseous emission from the flare
      pipe of the landfill site showed positive responses or toxic effects in 6 out of
      20 trips, and that from the incinerator showed positive responses in 5 out of the
      8 trips. These positive responses were closely associated with the weather, i.e.
      low wind velocity, high temperature and relative humidity, and especially the
      distance from the chimney of the incinerator. The MCN frequencies and mutation
      rates of the Elementary School site (E. Sch) which is about 200 m from the fence
      of the landfill site were mostly negative, except the test results of three
      trips. Trad-SHM tests on the mutagenicity of gaseous emissions from the flare
      pipe of the landfill showed 12 positive responses out of 20 trials and 2
      positives out of 4 trials from the incinerator gaseous emissions. The average
      mutation rate from 20 Trad-SHM monitoring trips is positive when the ANOVA and
      Dunnett's t-statistic were applied to the consolidated data. There is a
      significant (0.01) difference between the lab control and the gas exposed groups,
      and between the field control and gas exposed groups. Results of the Trad-SHM
      test at the E. Sch. site were mostly negative except for one trip. In general,
      micronuclei frequencies and mutation rates of the field control groups were
      relatively higher than those of the lab controls. The Trad-MCN test on pure gases
      showed positive responses in all 3 repeated tests on toluene (50-892 ppm). The
      test results of ethylbenzene yielded positive responses at 172 ppm/min and 1549
      ppm/min dosages and exhibited toxicity at higher concentrations. Trad-MCN tests
      on trichloroethylene and ethyltoluene yielded positive responses at around 100
      200 ppm/min level. Three repeated Trad-SHM tests on toluene yielded no positive
      response at low concentrations (4.3-12.9 ppm).

PMID- 8569802
TI  - Cytogenetic analysis of mice chronically fed the food mutagen 2-amino-1-methyl-6
      phenylimidazo[4,5b]pyridine.
AB  - The cytogenetic effects in mice chronically fed the heterocyclic amine 2-amino-1
      methyl-6-phenylimidazo[4,5b]pyridine (PhIP) were evaluated by chromosome
      painting, micronucleated normochromatic erythrocytes (MN NCEs) and sister
      chromatid exchanges (SCEs). PhIP and numerous other heterocyclic amines have been
      isolated from cooked foods, and many have been found to be carcinogenic in
      laboratory rodents. Female C57BL/6N mice were chronically fed a diet containing
      0, 100, 250 or 400 ppm of PhIP beginning at 8 weeks of age. Peripheral blood and
      bone marrow were taken from 5 mice per treatment group at 1, 4 and 6 months from
      the start of exposure. PhIP was removed from the diet for a final month of the
      experiment, at which time blood was taken from the remaining animals. Chromosome
      specific composite DNA probes for mouse chromosomes 2 and 8 were hybridized to
      metaphase cells from each tissue. The 1- and 4-month time points showed no
      statistically significant difference between the control and exposed mice for
      either tissue in chromosome aberration frequencies. Both MN NCEs and SCEs were
      analyzed at a single time point during exposure (4 months for MN NCEs and 6
      months for SCEs) and again 1 month after removing PhIP from the diet. MN NCEs in
      the peripheral blood showed a statistically significant dose response, with all
      values decreasing significantly 1 month after removing PhIP from the diet. SCE
      frequencies in the peripheral blood showed an approximate doubling compared to
      control mice, and decreased to control levels 1 month after removing PhIP from
      the diet. SCE frequencies in the bone marrow of exposed mice showed no difference
      from the control animals. These results show that chronic ingestion of PhIP by
      female C57BL/6 mice does not produce persistent cytogenetic damage as visualized
      by chromosome aberrations, MN NCEs or SCEs.

PMID- 8569803
TI  - Assessment of DNA damage in canine peripheral blood and bone marrow after total
      body irradiation using the single-cell gel electrophoresis technique.
AB  - DNA damage in single peripheral blood (pb) and bone marrow (bm) cells was studied
      in dogs which were exposed to total body X-ray irradiation (TBI) with a lethal
      dose of 3.9 Gy. The changes in pb and bm cell numbers were measured within 9 days
      after TBI. Using the alkaline single-cell gel electrophoresis technique ('comet'
      assay), DNA strand breaks and alkali labile sites were assessed in single cells
      derived from the blood before TBI, 1 h and 4 h after TBI and on days 1, 3 and 9
      after TBI. Bone marrow cells subjected to the assay were collected before and on
      days 1 and 9 after TBI. Cells expressing the strongest DNA damage were most
      frequent in the blood 1 h after TBI and in the bone marrow 1 day after exposure.
      Thereafter, a continuous reduction of DNA damage in individual cells was observed
      in the course of progressive leukopenia and granulocytopenia.

PMID- 8569804
TI  - Interaction of nickel with mutagens in the induction of sister chromatid
      exchanges in human lymphocytes.
AB  - In this study, individual treatments of human lymphocytes with Ni(II) [0.5-25
      microM], Cr(VI) [0.65-1.30 microM], UV-light or X-rays induced SCEs in a dose
      dependent fashion, and combined treatments of Ni(II) with Cr(VI), UV-light or X
      rays interacted antagonistically. Nickel, at environmentally relevant exposure
      levels, can have the effect in complex mixtures of reducing an otherwise positive
      SCE response and could lead to underestimating human exposures to certain classes
      of chemicals or radiation. Furthermore, our data indicate that antagonism may
      occur when human lymphocytes are exposed simultaneously to Ni(II) and Cr(VI),
      suggesting an explanation for epidemiological studies reporting conflicting
      results for cytogenetic effects in lymphocytes of workers exposed to chromium and
      nickel.

PMID- 8569805
TI  - European HPRT workshop in collaboration with GUM Gatersleben-Quedlinburg, 4-7
      May, 1995.

PMID- 8569806
TI  - Homage to Heinz P. R. Seeliger.

PMID- 8569807
TI  - Fluorescence assay for the detection of adherent Candida yeasts to target cells
      in microtest plates.
AB  - We describe an assay based on photometric analysis for the measurement of
      adherence of Candida species to epithelial target cells (Vero cell line).
      Adherent Candida cells were detected by staining the cells with the fluorescent
      dye Calcofluor white (CFW), which binds to chitin and glucan in the yeasts. The
      tests were performed on microtest plates, which were analysed automatically by
      fluorescence plate readers. The assay is based on the following steps: (i)
      coating of the microtest plates with target cells (e.g. Vero cells); (ii)
      infection with Candida: (iii) staining of Candida with CFW; (iv) rinsing to
      remove non-adherent Candida cells and unbound dye; (v) detection of adherent
      fluorescent Candida cells. The test was able to detect 4 x 10(4) cells ml-1. The
      standard deviation was +/- 8%. Day-to-day variation was +/- 10% at most. The
      adherence of strains of different Candida species was assayed by a standard
      procedure. The results confirmed the order of adherence, with C. albicans ranking
      first, followed by C. tropicalis, C. parapsilosis and C. glabrata.

PMID- 8569808
TI  - A carbohydrate-degrading enzyme from Candida albicans: correlation between alpha
      glucosidase activity and fungal growth.
AB  - Attempts to detect inducible carbohydrate-degrading enzymes from C. albicans were
      performed using carbohydrate-restricted media. Although alpha-amylase
      (polysaccharide hydrolase) was not induced from media containing starch or
      dextrin, alpha-glucosidase (disaccharide hydrolase) was induced from maltose
      containing medium. alpha-Glucosidase activity was detected from the intact cells
      in suspension and from the supernatant of both spheroplasted and mechanically
      broken cells, but not from the media. Enzyme activity in intact cells was pH
      independent and increased during logarithmic growth phase and in media containing
      lower concentrations of maltose. The addition of 5 mM 1-deoxynojirimycin, a
      competitive inhibitor of alpha-glucosidase, suppressed fungal growth by more than
      50%. These results suggest that alpha-glucosidase activity is crucial for fungal
      growth in medium containing maltose as a sole carbon source.

PMID- 8569809
TI  - Oral Candida carriage and blood group antigen secretor status.
AB  - Oral Candida carriage and blood group antigen secretor status were examined in 92
      healthy, young volunteers. Candida was isolated from 61 of 92 saliva samples (66%
      Candida carriage). In 76% of cases this was Candida albicans. Oral Candida
      carriage was found to be significantly associated with non-secretion of blood
      group antigens (P < 0.05). However, the numbers of Candida were higher in the
      saliva of secretors than of non-secretors (P < 0.01). A higher percentage of
      Candida carriage was observed in individuals with blood group O. Thus, the
      finding of higher carrier frequency in the non-secretors and in blood group O
      subjects is confirmed.

PMID- 8569810
TI  - An evaluation of seven methods of testing in vitro susceptibility of clinical
      yeast isolates to fluconazole.
AB  - Four commercially available in vitro test systems (Candifast, E-test, Mycototal
      and spiral-gradient end point method), agar diffusion with 25-micrograms
      fluconazole paper test discs and 15-micrograms test tablets and agar dilution
      were compared with the microbroth dilution method for fluconazole susceptibility
      testing of 145 clinical isolates. In addition, the culture media provided or
      recommended by the manufacturers of the test systems were compared with high
      resolution (HR) antifungal test medium. With all currently available culture
      media, growth problems (inhibition or delayed growth of the clinical isolates)
      occurred with solid or semisolid media. With minor improvements, HR medium
      demonstrated the most reproducible and comparable results (supplementation with
      asparagine and deletion of sodium hydrogen carbonate). The best correlation with
      microdilution was obtained by the agar dilution method (> 95% concordance)
      followed by the spiral-gradient end point method (85%), Candifast (83%),
      Mycototal (81%) and the E-test (78%). Regression analysis demonstrated good
      correlation between agar diffusion and micro-/agar dilution (r > 0.9).

PMID- 8569811
TI  - Arthritis without grains caused by Pseudallescheria boydii.
AB  - Severe infection of the knee joint by Pseudallescheria boydii in a 23-year-old
      female resulted in complete destruction of the cartilaginous surface. The
      possibility of entry of the fungus through mild abrasions of unperforated skin is
      discussed. The clinical appearance is compared with that of Scedosporium
      prolificans. Antimycotic miconazole-itraconazole treatment, applied during a
      period of 4 months, was successful; no side-effects were noted.

PMID- 8569812
TI  - Fatal fungaemia due to Sporothrix schenckii.
AB  - A clinical case is reported of a 78-year-old male with antecedents of diabetes
      and alcoholism who was hospitalized because he showed cutaneous lesions on the
      face and extremities suggesting cutaneous tuberculosis, but after a first
      histological study cutaneous leishmaniasis was erroneously diagnosed. Because of
      some unusual characteristics of the patient, the skin biopsies were carefully re
      examined, as well as blood smears, which revealed elongated yeast form-like cells
      suggestive of Sporothrix schenckii. The diagnosis was confirmed when the fungus
      grew in mice and in Sabouraud cultures inoculated with blood samples from the
      patient. It is recommended that Sp. schenckii is included in the differential
      diagnosis of ulcerative cutaneous lesions in patients from Mexican humid areas.

PMID- 8569813
TI  - Treatment of chronic disseminated Geotrichum capitatum infection with high
      cumulative dose of colloidal amphotericin B and itraconazole in a leukaemia
      patient.
AB  - A case of disseminated granulomatous Geotrichum capitatum infection is reported.
      A young patient with blastic crisis of chronic myelogenous leukaemia developed
      septicaemia caused by G. capitatum in the post-chemotherapy aplastic phase.
      Subsequently, disseminated infection of the liver, spleen, pancreas and kidneys
      was observed. Treatment with high cumulative doses of a lipid formulation of
      amphotericin B (Amphocil, 20.2 g in 11 weeks) and maintenance with itraconazole
      resolved clinical manifestations of G. capitatum granulomatous disseminated
      disease and controlled reactivation of the infection during the two subsequent
      courses of cytotoxic chemotherapy.

PMID- 8569814
TI  - Fungaemia in hospitalized patients.
AB  - At various clinics of IRCCS S. Matteo Hospital, Pavia, Italy, 269 blood cultures
      recovered from immunocompromised patients over 4 years have been examined
      mycologically. Of the 269 cultures, 101 were from HIV-infected patients and five
      were from cardiac transplant recipients. Of the total examined 96 blood cultures
      were positive (36%). The most frequent genus was Candida: C. albicans (48%), C.
      tropicalis and C. parapsilosis (8% each), C. glabrata and C. guillermondii (3%
      each). Cryptococcus neoformans was detected in 21 patients (22%).

PMID- 8569815
TI  - The anti-Malassezia furfur activity in vitro and in experimental dermatitis of
      six imidazole antifungal agents: bifonazole, clotrimazole, flutrimazole,
      ketoconazole, miconazole and sertaconazole.
AB  - Bifonazole, clotrimazole, flutrimazole, ketoconazole, miconazole and
      sertaconazole were tested for their activity against 23 isolates of Malassezia
      furfur by agar dilution in vitro. Topical formulations of the same agents were
      evaluated for efficacy against M. furfur skin infections in guinea pigs in vivo.
      The most potent inhibitor in vitro was ketoconazole (geometric mean minimum
      inhibitory concentration 0.51 microgram ml-1), followed by bifonazole (8.1
      micrograms ml-1), then miconazole (14 micrograms ml-1), clotrimazole (15
      micrograms ml-1) and flutrimazole (16 micrograms ml-1), with sertaconazole the
      least active (52 micrograms ml-1). In animal experiments involving three
      consecutive days of topical treatments, bifonazole 1% cream, clotrimazole 1%
      cream, flutrimazole 1% and 2% creams, ketoconazole 2% cream and shampoo and
      miconazole 2% cream all reduced M. furfur dermatitis lesion severity below that
      of untreated control animals; however, sertaconazole 2% gel and cream showed no
      reduction in lesion severity below control. The results confirm that ketoconazole
      is a more potent inhibitor of M. furfur in vitro than other topical antifungal
      agents of its class and suggest that sertaconazole is the least effective of such
      agents among those tested.

PMID- 8569816
TI  - A double-blind, randomized comparative trial: flutrimazole 1% solution versus
      bifonazole 1% solution once daily in dermatomycoses.
AB  - In a double-blind, randomized study the efficacy and tolerance of flutrimazole 1%
      solution were compared with bifonazole 1% solution, applied once daily for 4
      weeks, in 40 patients with culturally proven dermatophytosis or cutaneous
      candidosis. Forty patients with mycologically proven pityriasis versicolor were
      treated with once-daily application for 1 week. The four groups of patients and
      distribution of target lesions were similar, although in the flutrimazole group
      more patients had cutaneous candidosis (n = 8 versus n = 1). The distribution of
      the sum of clinical scores was also similar in both groups. At the end of therapy
      the proportion of patients with negative microscopy and culture was 85% in the
      flutrimazole group and 65% in the bifonazole group. There was a significant
      difference (P = 0.022) in terms of efficacy, since 80% of patients in the
      flutrimazole group versus 40% in the bifonazole group were judged to have
      received effective treatment. At the assessment 6 weeks after the end of therapy
      the percentages of flutrimazole- and bifonazole-treated patients with negative
      mycology were 75% and 65% respectively. There were two relapses (one in each
      group), which represents a 5% rate. Fifteen flutrimazole-treated patients (75%)
      compared with 12-bifonazole-treated patients (60%) had overall effective therapy.
      Two patients treated with bifonazole (10%) and one treated with flutrimazole (5%)
      had a premature termination due to adverse events attributable to the medication.
      On assessment 3 weeks after the end of treatment, the patients with pityriasis
      versicolor were all clinically and mycologically healed with negative
      fluorescence, including the patients who withdrew from the full course of
      treatment (one in each group). Nine weeks after the end of therapy all the
      patients remained cured, with no relapses. The overall incidence of adverse
      events (mild local reactions such as irritation, burning and itching) was one and
      seven cases for bifonazole and flutrimazole respectively. One patient in each
      group had to abandon treatment owing to severe intolerance.

PMID- 8569817
TI  - Isolation of dermatophytes from house dust on a medium containing gentamicin and
      flucytosine.
AB  - Dermatophytes are usually isolated from house dust by using actidione
      chloramphenicol Sabouraud glucose medium (ACS medium). We have prepared a new
      medium, 5FC medium, by adding gentamicin sulphate (GS) and 5-fluorocytosine (5FC)
      to ACS medium to achieve more efficient isolation of dermatophytes from house
      dust. 5FC medium was more effective in isolating dermatophytes than ACS medium or
      ACS medium supplemented with GS alone. Trichophyton rubrum could be grown from 13
      out of 19 house dust samples from the homes of patients with tinea pedis (68.4%),
      and T. mentagrophytes could be grown from 17 out of 21 (81.0%). Two of 20 house
      dust samples from the home of a control family without dermatophytosis grew only
      one colony of dermatophytes in 5FC medium; the rest of the samples showed no
      growth. The number of colonies isolated on 5FC medium was much higher than on ACS
      medium (5.3 vs. 2.0 for T. rubrum and 17.2 vs. 2.1 for T. mentagrophytes). In
      addition, the size of the isolated colonies was much larger than that on ACS
      medium. Thus, 5FC medium can be regarded as a useful tool for isolating
      dermatophytes from various contaminated samples.

PMID- 8569819
TI  - Epidemiology of dermatophytoses observed in Rome, Italy, between 1985 and 1993.
AB  - Between 1985 and 1993, 13,880 patients were studied for possible forms of
      dermatophytoses. The most frequently isolated dermatophyte was in 2821 positive
      cases Microsporum canis (50%), followed by Trichophyton rubrum (27%),
      Trichophyton mentagrophytes (10.6%), Epidermophyton floccosum (9.3%), Microsporum
      gypseum (2.3%), Trichophyton violaceum (0.6%), Trichophyton tonsurans (0.2%) and
      Trichophyton verrucosum (< 0.1%). The genera and species isolated were also
      considered in relation to the site of the lesion. Our epidemiological data were
      compared with those obtained by other authors in other cities and with those
      obtained in Rome in previous studies conducted between 1972-77 and 1978-83.
      Results obtained by various investigators in Europe are also discussed.

PMID- 8569818
TI  - Dermatophytes in northern Finland in 1982-90.
AB  - The epidemiology of human dermatophytes was studied in northern Finland in 1982
      90. The samples were analysed at the Department of Medical Microbiology,
      University of Oulu. The total number of samples was 17,822, of which 3185 (18%)
      were positive. The annual number of samples and positive cultures remained
      relatively constant. Trichophyton rubrum was the most common species being
      isolated from 2101 samples (66% of all positive cultures), while Trichophyton
      mentagrophytes was isolated from 815 samples (26%) and Epidermophyton floccosum
      from 193 samples (6%). T. verrucosum caused an epidemic among cattle keepers in
      1987-90, causing 47 infections. Microsporum canis, T. terrestre and T. violaceum
      were rare. The same species affected both children and adults. There was a
      tendency towards a decrease in tinea in the groin and a slight increase in tinea
      pedis. T. rubrum and T. mentagrophytes occurred most frequently in patients aged
      41-45 years and as foot infections. E. floccosum usually affected the toe web and
      the groin in patients aged 21-25 years, more often infecting men. Fifty-four per
      cent of all positive samples came from men and 46% from women.

PMID- 8569820
TI  - Aetiology of onychomycosis in Al Ain, United Arab Emirates.
AB  - A 1-year study was conducted on 151 patients with finger- or toenail disease
      attending a dermatology clinic in Al Ain, United Arab Emirates. Nail scrapings
      and or clippings were collected and investigated with a KOH preparation for
      direct microscopy and cultured for fungi. Eighty-nine (59%) patients were
      females. Most females (62%) presented with fingernail disease while in men the
      toenails were involved in 76%. Fungi were isolated in 78 (52%) of all cases and
      the fingernails were more commonly positive than toenails. Of the 78 isolates, 49
      (63%) were yeasts, including eight Candida species, dermatophytes accounted for
      22 (28%) and seven (9%) were other moulds. Non-dermatophyte moulds constituted
      20% of male isolates but only 4% of female isolates. Eighty-one per cent of
      Candida species were from fingernails, while 87% of all the dermatophytes were
      from toenails.

PMID- 8569821
TI  - Transmission of hepatitis B virus to multiple patients from a surgeon without
      evidence of inadequate infection control.
AB  - BACKGROUND: Although about 1 percent of surgeons are infected with hepatitis B
      virus (HBV), transmission from surgeons to patients is thought to be uncommon. In
      July 1992, a 47-year-old woman became ill with acute hepatitis B after undergoing
      a thymectomy in which a thoracic-surgery resident who had had acute hepatitis B
      six months earlier assisted. METHODS: To determine whether the surgeon
      transmitted HBV to this patient and others, we conducted chart reviews,
      interviews, and serologic testing of thoracic-surgery patients at the two
      hospitals where the surgeon worked from July 1991 to July 1992. Hepatitis B
      surface antigen (HBsAg) subtypes and DNA sequences from the surgeon and from
      infected patients were determined. RESULTS: Of 144 susceptible patients in whose
      surgery the infected surgeon participated, 19 had evidence of recent HBV
      infection (13 percent). One of the hospitals was selected for additional study,
      and none of the 124 susceptible patients of the other thoracic surgeons at this
      hospital had evidence of recent HBV infection (relative risk, infinity; 95
      percent confidence interval, 4.7 to infinity). No evidence was found for any
      common source of HBV other than the infected surgeon. The HBsAg subtype and the
      partial HBV DNA sequences from the surgeon were identical to those in the
      infected patients. Transmission of the infection was associated with cardiac
      transplantation (relative risk, 4.9; 95 percent confidence interval, 1.5 to 15.5)
      but not with other surgical procedures. The surgeon was positive for hepatitis B
      e antigen and had a high serum HBV DNA concentration (15 ng per milliliter). Our
      investigations identified no deficiencies in the surgeon's infection-control
      practices. CONCLUSIONS: In this outbreak there was surgeon-to-patient HBV
      transmission despite apparent compliance with recommended infection-control
      practices. We could not identify any specific events that led to transmission.

PMID- 8569822
TI  - Transmission of hepatitis C virus by a cardiac surgeon.
AB  - BACKGROUND: In the course of a study conducted in 1992 through 1994 of the
      efficacy of screening blood donors for antibodies to hepatitis C virus (HCV), we
      found that two patients had acquired hepatitis C after cardiac surgery, with the
      transmission apparently unrelated to blood transfusions. Because their surgeon
      had chronic hepatitis C, we sought to determine whether he was transmitting the
      virus to his patients. METHODS: Of 222 of the surgeon's patients who participated
      in studies of post-transfusion hepatitis between 1988 and 1994, 6 contracted
      postoperative hepatitis C, despite the use of only seronegative blood for
      transfusions. All six patients had undergone valve-replacement surgery. Analyses
      were performed to compare nucleotide sequences encompassing the hypervariable
      region at the junction between the coding regions for envelope glycoproteins E1
      and E2 in the surgeon, the patients, and 10 controls infected with the same HCV
      genotype. RESULTS: The surgeon and five of the six patients with hepatitis C
      unrelated to transfusion were infected with HCV genotype 3; the sixth patient had
      genotype 1 and was considered to have been infected from another source. Thirteen
      other patients of the surgeon had transfusion-associated hepatitis C and were
      also infected with genotype 1. The average net genetic distance between the
      sequences from the five patients with HCV genotype 3 and those from the surgeon
      was 2.1 percent (range, 1.1 to 2.5 percent; P < 0.001), as compared with an
      average distance of 7.6 percent (range, 6.1 to 8.3 percent) between the sequences
      from the patients and those from the controls. The results of phylogenetic-tree
      analysis indicated a common epidemiologic origin of the viruses from the surgeon
      and the five patients. CONCLUSIONS: Our findings provide evidence that a cardiac
      surgeon with chronic hepatitis C may have transmitted HCV to five of his patients
      during open-heart surgery.

PMID- 8569823
TI  - Three-year follow-up after implantation of metallic coronary-artery stents.
AB  - BACKGROUND: Coronary-artery stents are known to reduce rates of restenosis after
      coronary angioplasty, but it is uncertain how long this benefit is maintained.
      METHODS: We evaluated clinical and angiographic follow-up information for up to
      three years after the implantation of Palmaz-Schatz metallic coronary-artery
      stents in 143 patients with 147 lesions of native coronary arteries. RESULTS: The
      rate of survival free of myocardial infarction, bypass surgery, and repeated
      coronary angioplasty for stented lesions was 74.6 percent at three years. After
      14 months, revascularization of the stented lesion was necessary in only three
      patients (2.1 percent). In contrast, coronary angioplasty for a new lesion was
      required in 11 patients (7.7 percent). Follow-up coronary angiography of 137
      lesions at six months, 114 lesions at one year, and 72 lesions at three years
      revealed a decrease in minimal luminal diameter from 2.54 +/- 0.44 mm immediately
      after stent implantation to 1.87 +/- 0.56 mm at six months, but no further
      decrease in diameter at one year (in patients with paired angiograms, 1.95 +/-
      0.49 mm at both six months and one year). Significant late improvement in luminal
      diameter was observed at three years (in patients with paired angiograms, 1.94 +/
      0.48 mm at six months and 2.09 +/- 0.48 mm at three years; P < 0.001).
      CONCLUSIONS: Clinical and angiographic outcomes up to three years after coronary
      artery stenting were favorable, with a low rate of revascularization of the
      stented lesions. Late improvement in luminal diameter appears to occur between
      six months and three years.

PMID- 8569824
TI  - The length of the cervix and the risk of spontaneous premature delivery. National
      Institute of Child Health and Human Development Maternal Fetal Medicine Unit
      Network.
AB  - BACKGROUND: The role of the cervix in the pathogenesis of premature delivery is
      controversial. In a prospective, multicenter study of pregnant women, we used
      vaginal ultrasonography to measure the length of the cervix; we also documented
      the incidence of spontaneous delivery before 35 weeks' gestation. METHODS: At 10
      university-affiliated prenatal clinics, we performed vaginal ultrasonography at
      approximately 24 and 28 weeks of gestation in women with singleton pregnancies.
      We then assessed the relation between the length of the cervix and the risk of
      spontaneous preterm delivery. RESULTS: We examined 2915 women at approximately 24
      weeks of gestation and 2531 of these women again at approximately 28 weeks.
      Spontaneous preterm delivery (at less than 35 weeks) occurred in 126 of the women
      (4.3 percent) examined at 24 weeks. The length of the cervix was normally
      distributed at 24 and 28 weeks (mean [+/- SD], 35.2 +/- 8.3 mm and 33.7 +/- 8.5
      mm, respectively). The relative risk of preterm delivery increased as the length
      of the cervix decreased. When women with shorter cervixes at 24 weeks were
      compared with women with values above the 75th percentile, the relative risks of
      preterm delivery among the women with shorter cervixes were as follows: 1.98 for
      cervical lengths at or below the 75th percentile (40 mm), 2.35 for lengths at or
      below the 50th percentile (35 mm), 3.79 for lengths at or below the 25th
      percentile (30 mm), 6.19 for lengths at or below the 10th percentile (26 mm),
      9.49 for lengths at or below the 5th percentile (22 mm), and 13.99 for lengths at
      or below the 1st percentile (13 mm) (P < 0.001 for values at or below the 50th
      percentile; P = 0.008 for values at or below the 75th percentile). For the
      lengths measured at 28 weeks, the corresponding relative risks were 2.80, 3.52,
      5.39, 9.57, 13.88, and 24.94 (P < 0.001 for values at or below the 50th
      percentile; P = 0.003 for values at the 75th percentile). CONCLUSIONS: The risk
      of spontaneous preterm delivery is increased in women who are found to have a
      short cervix by vaginal ultrasonography during pregnancy.

PMID- 8569825
TI  - Images in clinical medicine. Knotted umbilical cord.

PMID- 8569826
TI  - Metformin.

PMID- 8569827
TI  - Seminars in medicine of the Beth Israel Hospital, Boston. Adrenergic receptors-
      evolving concepts and clinical implications.

PMID- 8569828
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 7-1996. An eight-year-old boy with intractable seizures.

PMID- 8569829
TI  - The infected health care provider.

PMID- 8569831
TI  - Our ailing public hospitals.

PMID- 8569830
TI  - Cervical incompetence and preterm delivery.

PMID- 8569832
TI  - Our ailing public hospitals.

PMID- 8569833
TI  - Our ailing public hospitals.

PMID- 8569834
TI  - Blood glucose monitoring in gestational diabetes mellitus.

PMID- 8569835
TI  - Blood glucose monitoring in gestational diabetes mellitus.

PMID- 8569836
TI  - Blood glucose monitoring in gestational diabetes mellitus.

PMID- 8569837
TI  - Apolipoprotein E and the neuropathology of dementia.

PMID- 8569838
TI  - Maintenance therapies for reflux esophagitis.

PMID- 8569839
TI  - Maintenance therapies for reflux esophagitis.

PMID- 8569840
TI  - Anticytomegalovirus T-cell clones.

PMID- 8569842
TI  - Lichen planus after consumption of a gold-containing liquor.

PMID- 8569841
TI  - Chromosomal translocations in secondary acute myeloid leukemia.

PMID- 8569843
TI  - Introducing a market to the United Kingdom's National Health Service.

PMID- 8569844
TI  - Trans fatty acids: implications for health, analytical methods, incidence in
      edible fats and intake (a review).
AB  - Trans fatty acids (TFA) are supposed to be related to a variety of physiological
      effects. Numerous studies in this field are gathered and compared, which mainly
      deal with the influences on lipoprotein levels in plasma and their effects with
      regard to coronary heart diseases. Furthermore, the analytical accessibility of
      trans fatty acids by different methods is presented. Thus, the most reliable
      method for an exact quantitation of trans fatty acids in edible fats is the
      combination of Ag-TLC with GC. The contents of TFA, in particular trans
      octadecenoic acids, in bovine and human milk fat, in partially hydrogenated
      vegetable fats and oils as well as in processed food from different countries,
      determined in numerous studies, are summarized. Especially results on the
      isomeric distribution of positional isomers of trans-octadecenoic acid may be of
      future interest, since negative metabolic activities might only originate from
      certain isomers. Finally, intake rates of TFA in several countries are presented.
      It can be concluded that there still is need for further nutritional studies and
      that the discussion about TFA should not neglect the comparison with the
      saturated fatty acids C12, C14 and C16.

PMID- 8569845
TI  - Changes in histological structure and physiochemical properties of raw, cured,
      smoked pork loins resulting from freezing near cryoscopic temperature.
AB  - The aim of the study was to determine the effects of unintended freezing during
      cold storage (deep chilling conditions) and low freezing temperatures (-10
      degrees C) of raw pork loins, cured and smoked, on their histological structure
      and some physicochemical characteristics. The experimental products after
      freezing at -10 degrees C, were stored at the same temperature for 0, 2, 4 and 6
      days, thawed thereafter and immediately deep chilled at near cryoscopic
      temperature (-3 degrees C) for 0, 2, 4 or 6 days. These conditions were changing
      the histological structures of pork loin, the water holding capacity (WHC) was
      reduced by frozen storage but improved by deep chilling; the maximum shear force
      and energy were increased. The more the freezing at -10 degrees C was prolonged,
      the more unfavourable were the changes in structure, WHC and tenderness. Deep
      chilling at -3 degrees C after thawing of the experimental material on the other
      hand favourably affected the parameters measured. Freezing at -10 degrees C and
      deep chilling at -3 degrees C did not affect the electrophoretic picture of pork
      loin proteins nor the water activity. Freezing itself had no influence on WHC.
      Changes were due to storage.

PMID- 8569846
TI  - Plasma fatty acid profile and prooxidative-antioxidative parameters in
      vegetarians.
AB  - Fatty acid profile in plasma was examined in 12 adult vegetarians (lacto and
      lacto-ovo) aged 41-63 years with an average period of vegetarian nutrition of 9.8
      years. Difference in the content of saturated and monounsaturated fatty acids in
      vegetarians was insignificant (compared to non-vegetarians). Positive factor of
      vegetarian nutritional habit with respect to atherosclerosis included
      significantly elevated content of linoleic acid (C 18:2) and linolenic acid (C
      18:3), as well as unchanged or only slightly reduced content of polyunsaturated
      fatty acids--arachidonic acid (C 20:4) and docosahexaenoic acid (C 22:6, n = 3).
      Favourable values of prooxidative-antioxidative parameters (significantly reduced
      content of conjugated dienes of fatty acids in plasma, significantly higher
      plasma levels of vitamin C, beta-carotene, vitamin E/cholesterol--indicator of
      LDL protection and vitamin E/triacylglycerols--indicator of fatty acid
      protection) demonstrated a reduced risk of lipoperoxidation in vegetarians.

PMID- 8569847
TI  - Some aspects of reactions of benzyl isothiocyanate with bovine sarcoplasmic
      proteins.
AB  - Benzyl-ITC (benzyl isothiocyanate) reacts preferentially with amino groups and
      sulfhydryl side chains of bovine sarcoplasmic proteins to form thiourea and
      dithiocarbamate derivatives, generally resulting in a decrease in solubility of
      the derivatives along a wide pH range. Under these conditions, it was also
      possible to show that secondary amine side chains, as found in tryptophan, also
      react with benzyl-ITC. A quenching of tryptophan fluorescence intensity after
      interaction with benzyl-ITC was also observed. Polyacrylamide gel electrophoresis
      (PAGE) experiments in the presence of urea indicated changes in electrophoretical
      mobility and in composition of subfractions. Changes in surface hydrophobicity
      and composition as determined by the ANS (8-anilinonaphthalene-1-sulfonate)
      method and RP-HPLC were also observed. Polymerisation of protein molecules after
      reaction with benzyl-ITC was documented using the SDS-PAGE technique. These
      investigations showed that a group of subfractions belonging mainly to glycolytic
      enzymes and associated proteins with molecular weight between 38-70 kDa was
      highly reactive.

PMID- 8569850
TI  - [Australian short-beaked echidna].
AB  - The Australian short-beaked echidna, a monotreme, is one of the oldest living
      mammals on earth. It is recorded to be the most widely distributed native mammal
      on the island continent and classed as 'common'. Yet, little is known about its
      natural history and biology in the wild. What science has learned about the
      echidna in the past 200 years and why there are still large gaps is reported
      here.

PMID- 8569851
TI  - Transsaccadic visual matching: evidence for a foveal-extrafoveal cooperation
      across saccadic eye movements.

PMID- 8569849
TI  - The fates of proteins in cells.
AB  - Nascent polypeptide chains are in a dangerous situation as soon as they leave
      their place of birth, the channel of the large ribosomal subunit: more than 20
      different pathways for the degradation of proteins exist in cells. Chaperones
      protect and guide the young protein molecules and support their correct foldings.
      Targeting signals direct the proteins to the organelles of their destination. The
      lysosome is the site of random degradation, while the proteasome is highly
      selective. Although these two organelles provide the most important pathways for
      the degradation of long- and short-lived proteins, other pathways with roles in
      deciding the fate of cellular proteins must also be considered.

PMID- 8569848
TI  - [Protein-carbohydrate recognition. Foundation and medical application with
      illustrations of tumor lectin studies].
AB  - Protein-carbohydrate interactions are involved in multifarious physiological
      processes. Together with antibodies and enzymes, lectins constitute the family of
      carbohydrate-binding proteins. The current research activities of tumor
      lectinology comprise the design of custom-made carrier-immobilized carbohydrate
      ligands (neoglycoconjugates), their application for the detection of specific
      binding sites and the evaluation of potential therapeutical approaches by
      blocking access or by directing drug conjugates to cell surface lectins,
      correlation of their expression to clinical parameters such as prognosis and
      their biochemical characterization. Thereby, mammalian lectins are made available
      to serve as tools. These experimental approaches are evaluated as regards their
      potential for improving cancer diagnosis and therapy.

PMID- 8569852
TI  - Farewells to a friend. Honoring Dr. Robert W. Prichard.

PMID- 8569853
TI  - Abraham Flexner and medical education in North Carolina.

PMID- 8569854
TI  - Health care costs. Lessons from 1932 about a chronic crisis.

PMID- 8569855
TI  - Davis Hospital. A manifestation of Dr. James Davis.

PMID- 8569856
TI  - Dr. Edmund Burke Haywood and Civil War medicine in Raleigh, North Carolina.

PMID- 8569857
TI  - Caught in Clio's grip. My romance with the muse of [medical] history.

PMID- 8569858
TI  - UNC's deans of medicine. Reminiscences of a septugenarian.

PMID- 8569859
TI  - The North Carolina Mutual Life Insurance Company, Dr. Clyde Henry Donnell, and
      the health education of blacks.

PMID- 8569860
TI  - The Carolinas' contribution to the education of Dr. Richard Bright.

PMID- 8569861
TI  - A Civil War epidemic. Yellow fever in Wilmington, North Carolina, 1862.

PMID- 8569862
TI  - Multiple hereditary telangiectases with recurring hemorrhage. A rare disease of
      clinical interest to Osler.

PMID- 8569863
TI  - The history of visceral larva migrans at the Bowman Gray School of Medicine.

PMID- 8569864
TI  - [Social phobia].

PMID- 8569865
TI  - [Evisceration of the small intestine due to rectum rupture].
AB  - Evisceration of the small intestine from the anus due to a rectal rupture was
      diagnosed in two patients, males aged 93 and 25 years. The former had had a
      rectal prolapse for years; the evisceration occurred after a fall from the bed.
      The lower abdomen of the second patient was caught between the counterweight of a
      bridge and a wall. Laparotomy in both patients revealed a rupture in the ventral
      portion of the rectosigmoid, but no pre-existent lesions in this part of the
      intestinal wall. Treatment in the first patient consisted of resection of the
      rectosigmoid with creation of an end colostomy, the eviscerated intestinal tract
      being repositioned in the abdominal cavity after thorough cleansing. In the
      second patient the eviscerated intestinal tract had to be resected. In this case
      also, an end colostomy was created and the rupture in the rectum was closed
      transanally. Both patients recovered well.

PMID- 8569866
TI  - [Spinal dural arteriovenous fistula: a treatable cause of loss of strength in the
      legs].
AB  - In a 59-year-old male suffering from progressive gait disorder with paraparesis
      and sensory disturbances in the legs, two spinal dural arteriovenous fistulas on
      levels Tv and LIII were demonstrated by spinal angiography. Both fistulas were
      embolised with glue, which resulted in complete relief of his symptoms. Spinal
      dural arteriovenous fistulas are localized in the dura, extramedullary, and are
      most often found in males over forty. Signs and symptoms are caused by venous
      congestion and ischaemia of the spinal cord. Treatment is by means of
      embolisation or surgical ligation. Early diagnosis and treatment are important,
      since delay causes development of irreversible myelopathy.

PMID- 8569868
TI  - [Cervical avulsion fracture caused by an air bag].
AB  - In a 30-year-old man who had crashed his car into a stationary vehicle at a speed
      of 100 km/h, after which an airbag inflated, a fracture of the spinous process
      CVII was diagnosed. The patient had not used a seat belt. This injury has not
      previously been reported in the literature as an airbag related injury. The
      patient was very tall (2.00 m) which probably led to hyperflexion of the cervical
      spine over the airbag.

PMID- 8569867
TI  - [General argyria caused by administration of tobacco-withdrawal tablets
      containing silver acetate].
AB  - In a 49-year-old man generalised argyria was diagnosed, a systemic dissemination
      and tissue deposition of silver in the body. The clinical picture was brought
      about by use of a silver acetate-containing lozenge as a deterrent to smoking.
      Argyria is characterised by a slate blue-gray discolouration of the skin,
      particularly in areas exposed to light. Generally, it causes patients a great
      deal of anguish and embarrassment. Present understanding is that it does not
      entail non-cutaneous, systemic effects. There is no effective treatment--the
      discolouration is permanent. Currently, prevention is the only possible measure.
      Efforts should be made to eliminate the uncontrolled use of silver-containing
      preparations.

PMID- 8569869
TI  - [Light therapy in 3 children with winter depression].
AB  - In three children, boys of 5 and 13 years old and a girl aged 10, seasonal
      affective disorder was diagnosed based on mood changes (listlessness, fears) and
      increased sleepiness in the winter season. They were treated successfully with
      light therapy (5 consecutive days 30 min 10,000 lux of full spectrum light
      without ultraviolet). In two patients the disorder recurred in the fall/winter
      the year(s) thereafter, and they were again treated successfully.

PMID- 8569870
TI  - [Severe poisoning by 4-aminopyridine in a body builder].
AB  - A 22-year-old man was admitted to hospital with severe, accidental intoxication
      with 4-aminopyridine, a medicine which increases the acetylcholine concentration
      in the synapses and has a limited application in the treatment of some
      neurological diseases. The patient acted on the assumption of body-building
      capacities of this 'amino'. Apart from the previously documented symptoms of
      intoxication such as an epileptic attack and confusion, he showed cardiac
      arrhythmias, conduction disorders and severe hypertension. The serum
      concentration of 4-aminopyridine was 335 mg/l, while the therapeutic level is 25
      75 mg/l.

PMID- 8569871
TI  - [Ergotism and the Isenheimer altar].

PMID- 8569872
TI  - [The history of tracheotomy].

PMID- 8569873
TI  - [Romberg's test; a century of discord over its implementation].

PMID- 8569874
TI  - [Physicians on current coins].

PMID- 8569875
TI  - [William Sinclair, Scottish student in medicine in Leiden, 1736-1737].

PMID- 8569876
TI  - [In search of the blue whales].

PMID- 8569877
TI  - [Minor symptoms in family medicine; chloasma or 'pregnancy mask'].

PMID- 8569878
TI  - [Schistosomiasis after swimming in the lake of Malawi].

PMID- 8569879
TI  - [Belle epoque?].

PMID- 8569880
TI  - [Farewell to Dunning].

PMID- 8569881
TI  - [TIA... an aspirin?].

PMID- 8569882
TI  - [Nobel Prize for Medicine/Physiology 1995].

PMID- 8569883
TI  - [Molecular-genetic detection of colorectal carcinoma in the feces].

PMID- 8569884
TI  - [Long-term treatment with calcium antagonists: advantageous effects and risks].

PMID- 8569885
TI  - [Neurocysticercosis].

PMID- 8569886
TI  - [Insufficient participation in prevention programs for infants by Turkish,
      Moroccan, Chinese and Vietnamese parents in large cities].
AB  - OBJECTIVE: To establish the participation in a number of effective prevention
      programmes for infants of Turkish, Maroccan, Chinese and Vietnamese inhabitants
      of the four major cities in the Netherlands. DESIGN: Enquiry. SETTING: Health
      centres in Amsterdam, Rotterdam, The Hague and Utrecht. METHOD: Health centre
      staff members in 1994 asked 194 Turkish and 158 Maroccan parents to participate
      in the study: the responses were 142 (73%) and 104 (66%), respectively. With the
      aid of Chinese and Vietnamese female interpreters, 44 parents of Chinese and 75
      of Vietnamese infants were persuaded to participate. Previously instructed
      interviewers presented the parents of all children with a number of structured
      questions in their own languages regarding use of vitamins (A)D and K and about
      vaccination against diphtheria, pertussis, tetanus and poliomyelitis (DKTP) and
      with BCG vaccine. RESULTS: Bottle feeding alone was given to 18% of the Turkish,
      43% of the Maroccan, 71% of the Chinese and 51% of the Vietnamese children. 82%
      Of the children were given vitamin A(D), the Maroccan children the most and the
      Vietnamese children the least often. Of the breast-fed children, 65% were given
      vitamin K, the Turkish children the most often. The DKTP vaccination degrees
      (1st, 2nd and 3rd vaccination) of the Turkish, Vietnamese and Chinese children
      was in accordance with those of Dutch children, but of the Maroccan children, one
      in five had not been vaccinated according to the parents. The BCG vaccination
      degrees were too low among the Turkish (55%) and the Maroccan (42%) children. Of
      the mothers, 27% reported having been vaccinated against rubella; 2% had
      vaccination certificates. CONCLUSION: Participation of the four groups of
      allochtonous children in the effective prevention programmes investigated was
      insufficient. At contacts of health workers with these groups, participation in
      prevention programmes should always be established. Support by means of educative
      material to be developed specifically should be made a subject of research.

PMID- 8569888
TI  - [2 patients with neurocysticercosis].
AB  - Cysticercosis of the CNS, caused by the pork tapeworm Taenia solium, was
      diagnosed on the basis of serological and imaging examination in two patients, a
      woman aged 50 and a man aged 40 years. The former patient suffered from aphasia,
      headache and epileptic attacks, the latter mostly from epilepsy. Cysticercosis of
      the CNS occurs mainly in the tropics but is occasionally observed in the
      Netherlands in people who have been to the tropics, such as the patients
      reported. Both ultimately recovered after drug therapy which included
      praziquantel.

PMID- 8569887
TI  - [Sluder's adenotonsillectomy: with or without endotracheal intubation?].
AB  - OBJECTIVE: To assess differences in results and complications of
      adenotonsillectomy according to Sluder in children anaesthesized with or without
      endotracheal intubation. DESIGN: Retrospective descriptive study. SETTING: Ear,
      Nose and Throat department, Academic Hospital Nijmegen, the Netherlands. METHOD:
      The medical records were reviewed of 1011 children (511 non-intubated, before
      1992, 500 intubated), and a questionnaire was sent to the parents regarding the
      postoperative period. RESULTS: The total proportion of postoperative haemorrhage
      was 4.35%; 5.1% in the non-intubated group, 3.6% in the intubated group (p >
      0.05). In the intubated group there were more patients with postoperative fever
      (p < 0.01) but fewer with tonsillar remnants (p < 0.005). The procedure with
      intubation anesthesia took significantly more time (18 min versus 11 min).
      CONCLUSION: In a training situation the intubated procedure is advised because of
      available time. This does not apply to experienced specialists, who may even have
      fewer complications.

PMID- 8569889
TI  - [Echinococcus cyst in a young Dutch woman].
AB  - In a 32-year-old female patient, born and grown up in the Netherlands,
      echinococcal cysts were diagnosed in the lung and the liver. She had probably
      been infected seven years earlier on a holiday in Turkey. She recovered after
      surgical removal of the cysts under albendazole treatment.

PMID- 8569890
TI  - [From the library of the Nederlands Tijdschrift voor Geneeskunde: Heinrich
      Haeser's Textbook of the History of Medicine (1811-1884), translated into Dutch
      by Abraham Hartog Israels].

PMID- 8569892
TI  - [Physician and language].

PMID- 8569891
TI  - [Incompetency, medical practice and 3rd-party interests: where are the
      borderlines?].

PMID- 8569893
TI  - [2 new paintings for the Nederlands Tijdschrift voor Geneeskunde].

PMID- 8569894
TI  - [Decrease in mortality in coronary heart diseases in the period 1974-1992 largely
      explainable by changes in the risk factors cholesterol and smoking].

PMID- 8569895
TI  - [Stomach-friendly NSAIDs: careful optimism?].

PMID- 8569896
TI  - [Is there a relationship between alcoholism and the chance of traffic
      accidents?].

PMID- 8569897
TI  - [Variation in fertility studies in The Netherlands].

PMID- 8569898
TI  - [Osteomyelitis as complication of BCG vaccination].

PMID- 8569899
TI  - [Reasons to report or not report side effects of drugs to the national monitoring
      system in The Netherlands].

PMID- 8569900
TI  - [On nostalgia and humility].

PMID- 8569901
TI  - [Internet, telemedicine and electronic information services by the Nederlands
      Tijdschrift voor Geneeskunde].

PMID- 8569902
TI  - [Telecommunication, telemedicine and telesurgery].

PMID- 8569903
TI  - [Overdose of a drug with delayed action].

PMID- 8569904
TI  - [Focal nodular hyperplasia of the liver: assessment of diagnosis and treatment in
      31 patients in 15 years].
AB  - OBJECTIVE: Analysis of the diagnostic approach, therapy and management of focal
      nodular hyperplasia (FNH) of the liver. SETTING: University Hospital Rotterdam
      Dijkzigt, Rotterdam. DESIGN: Retrospective follow-up analysis. METHOD: Medical
      records of patients with histologically proven FNH were analysed with respect to
      complaints, diagnostic approach and therapeutic management. Follow-up took place
      at the outpatient clinic where history-taking, physical examination,
      ultrasonography and hepatitis B and C serology tests were performed. RESULTS:
      Thirty-one patients with histologically proven focal nodular hyperplasia were
      treated: 19 were treated conservatively, 12 underwent hepatic resection; one of
      these patients died postoperatively. Follow-up investigation was carried out in
      16 and 9 patients, respectively. Laboratory results did not contribute to the
      diagnosis. Computed tomography was the most reliable imaging method; 71% of the
      lesions were correctly diagnosed. After a median follow-up of 52 months none of
      the patients treated conservatively showed tumour growth on ultrasonography.
      CONCLUSIONS: The most efficient approach to confirm the diagnosis of focal
      nodular hyperplasia consists of an ultrasound-guided needle biopsy and
      histological examination of the specimen. Conservative management is the
      treatment of choice in focal nodular hyperplasia. Hepatic resection should only
      be performed in symptomatic patients, in case of tumour growth or of uncertain
      histological diagnosis, to exclude a malignant process.

PMID- 8569905
TI  - [Occult blood studies of the feces obsolete].

PMID- 8569906
TI  - [Children with acute lymphoblastic leukemia: prognostic significance of
      polymerase-chain-reaction analysis of minimal residual disease].
AB  - OBJECTIVE: Determination of the usefulness of polymerase chain reaction (PCR) for
      the detection of minimal residual disease (MRD) in bone marrow in children
      suffering from progenitor-B cell acute lymphoblastic leukaemia during and after
      treatment. DESIGN: Descriptive. SETTING: Emma's Children's Hospital, Academic
      Medical Centre, University of Amsterdam and Central Laboratory of the Dutch Red
      Cross, Amsterdam. METHOD: Of 50 children suffering from progenitor-B cell ALL,
      stored bone marrow samples and bone marrow slides were investigated: 328 bone
      marrow samples were analysed by PCR for IgH/TCR delta; 34 patients were analysed
      at the end of induction therapy. Follow-up period was 20 to 133 months. RESULTS:
      Twenty-two patients stayed in continuous complete remission (CCR), 28 patients
      experienced a recurrence (REC). Reduction of tumour mass was higher in the CCR
      group. At the end of induction therapy 2/18 CCR patients and 10/16 REC patients
      were PCR positive (p = 0.005). PCR positivity was not related with known
      prognostic factors. After recurrence 6/8 patients, who became PCR negative,
      stayed in remission. All patients who stayed positive after treatment for their
      recurrence died from leukaemia (p = 0.006). All children who were only temporary
      PCR negative suffered a recurrence. CONCLUSION: Analysis of MRD by means of PCR
      on bone marrow samples during and after treatment for progenitor-B cell ALL is of
      prognostic importance.

PMID- 8569907
TI  - [Pancreatogenic panniculitis].
AB  - A 40-year-old woman who had been treated for mesangiocapillary glomerulonephritis
      by renal transplantation, and who still used furosemide, azathioprine,
      cyclosporine and prednisone, was admitted with multiple erythematous nodes on the
      lower legs. Pancreatogenic panniculitis caused by pancreatitis was diagnosed. The
      patient died with a haemorrhagic and necrotic pancreas one month after admission.
      Pancreatogenic panniculitis occurs in 2-3% of patients with pancreatitis or
      pancreatic carcinoma. It can be a first manifestation of an undetected pancreatic
      disease.

PMID- 8569908
TI  - [Systemic fat necrosis and septic arthritis in acute pancreatitis].
AB  - Systemic fatty necrosis secondary to acute pancreatitis was diagnosed in a 47
      year-old man with high fever and painful nodules on the arms and the upper legs.
      This was complicated by fatal septic shock, septic arthritis and extensive soft
      tissue infections with Enterobacter cloacae, which was unsuccessfully treated
      with several antibiotic regimens, and from which the patient died.

PMID- 8569909
TI  - [Acute pancreatitis caused by chylomicronemia syndrome].
AB  - Pancreatitis caused by chylomicronaemia was diagnosed in three patients, two men
      of 36 and 51 years and a woman of 33 years. All three patients had a combined
      hyperlipidaemia, with severely elevated levels of triglycerides and cholesterol.
      Secondary causes of hypertriglyceridaemia such as uncontrolled diabetes mellitus,
      alcohol abuse, and non-compliance with diet and lipid lowering drug therapy
      caused aggravation of the lipid disorder. It is important to consider
      chylomicronaemia as a possible cause of pancreatitis, as treatment of the lipid
      disorder with diet and, if necessary, drugs can prevent recurrence of
      pancreatitis.

PMID- 8569910
TI  - [Acute pancreatitis caused by metronidazole].
AB  - A 45-year-old woman in the period 1988-1995 suffered three episodes of acute
      pancreatitis associated with the use of metronidazole. On each occasion the
      pancreatitis subsided after withdrawal of metronidazole. Pancreatitis is a very
      infrequent, but potentially dangerous adverse effect of metronidazole. The exact
      pathogenetic mechanism of metronidazole-induced pancreatitis remains to be
      determined.

PMID- 8569911
TI  - [Physician and Internet].

PMID- 8569912
TI  - [From Dunning to van Gijn].

PMID- 8569913
TI  - [Immunization from a socio-scientific viewpoint].

PMID- 8569914
TI  - [Risks of intracytoplasmatic sperm cell injection for offspring?].

PMID- 8569915
TI  - [Internationalization of medical education].

PMID- 8569916
TI  - [Should the function of general hospital physicians be standardized?].

PMID- 8569917
TI  - [Systematic approach to a difficult diagnostic problem].

PMID- 8569918
TI  - [Freud and hysteria: 1895-1995].

PMID- 8569919
TI  - [Osteoporosis, and then?].

PMID- 8569920
TI  - [Total mesorectal excision: a new standard for surgical treatment of rectal
      carcinoma].

PMID- 8569921
TI  - [Standard 'Pelvic inflammatory disease' of the Dutch Society of Family
      Physicians; reaction from the viewpoint of family practice].

PMID- 8569922
TI  - [Standard 'Pelvic inflammatory disease' of the Dutch Society of Family
      Physicians, from the viewpoint of gynecology].

PMID- 8569923
TI  - [Administration of vitamin D3 and its active metabolites in the prevention and
      treatment of osteoporosis].

PMID- 8569924
TI  - [Current viewpoints in the pathophysiology and treatment of muscle weakness in
      elderly men].

PMID- 8569925
TI  - [Treatment of asthma; are there still questions?].

PMID- 8569926
TI  - [Synopsis of the standard 'Pelvic inflammatory disease' of the Dutch Society of
      Family Physicians].

PMID- 8569927
TI  - [Serum screening in pregnant women for Down syndrome and open neural-tube
      defects; testing against the Health Council criteria for genetic screening].
AB  - OBJECTIVE: To check whether serum screening for Down syndrome and open neural
      tube defects satisfies the criteria set by the 'Committee Genetic screening' of
      the Dutch Health Council. DESIGN: Theoretical evaluation. METHOD: Serum screening
      (the combined serum assessment of alpha-fetoprotein, human chorionic
      gonadotrophin and unconjugated oestriol, taking into consideration maternal age)
      was assessed against the Dutch Health Council criteria. The absolute criteria
      could be subdivided into a group of general conditions not related to a
      particular screening programme, and a group of programme-specific conditions.
      RESULTS: Population serum screening satisfied some of the absolute criteria,
      while the programme-specific conditions should be realised in an actual screening
      programme. Psychological and community consequences of such a screening have not
      yet been investigated in the Dutch population.

PMID- 8569928
TI  - [Opportunistic lung infections in patients with chronic obstructive lung disease;
      a side effect of inhalation corticosteroids?].
AB  - In four patients, men of 64, 66 and 69 years old and a woman of 65 years, who
      suffered from chronic obstructive pulmonary disease (COPD) and used inhalation
      corticosteroids in a relatively high dose (800-1600 micrograms of budesonide per
      day), a pulmonary infection was diagnosed caused by Mycobacterium malmoense (the
      first two patients) and Aspergillus (the other two) respectively. Inhalation
      corticosteroids are of great importance in the treatment of asthmatic patients.
      Their place in the treatment of patients with COPD is much less clear. The
      patients did not have an immunological deficiency or anatomical pulmonary or
      bronchial deformation which could have explained the occurrence of these
      infections. The high dosages of inhalation corticosteroids may have been involved
      in the cause of these infections by suppressing the T-cell response locally. In
      view of this, longterm inhalation corticosteroid treatment should be prescribed
      in COPD patients only if the efficacy of the medication has been proved in the
      individual patient involved.

PMID- 8569929
TI  - [Alarming increase in deptropine poisonings].

PMID- 8569930
TI  - Adverse drug reactions: the role of the internist.

PMID- 8569931
TI  - Genotype, serum level of HCV-RNA and response to interferon-alpha treatment in
      patients with chronic hepatitis C.
AB  - OBJECTIVE: Since only a small proportion of patients with chronic hepatitis C
      benefit from interferon therapy, we assessed the viral factors such as HCV
      genotype and the level of viraemia for prediction of interferon response.
      METHODS: HCV genotype and serum levels of HCV-RNA were determined in 24 patients
      before, during and after interferon treatment. RESULTS: Pre-treatment serum
      levels of HCV-RNA were significantly lower in patients with normalization of
      serum ALT and disappearance of serum HCV-RNA upon therapy than in patients with
      persistent abnormal ALT and/or serum HCV-RNA positivity. Sole infection with HCV
      genotype 1b was associated with a significantly higher pre-treatment serum HCV
      RNA level than infection with genotype other than 1b or mixed types. CONCLUSIONS:
      HCV genotype and pre-treatment serum HCV-RNA levels are indeed important
      predictors for response to interferon treatment in patients with chronic
      hepatitis C.

PMID- 8569932
TI  - Serodiagnosis of Helicobacter pylori infection: an evaluation of a commercially
      available ELISA-IgG.
AB  - BACKGROUND: Our aim was to evaluate a commercially available ELISA (Pyloriset
      IgG, Orion diagnostica, Imphos B.V.) for detection of serum IgG antibodies to
      Helicobacter pylori. METHODS: Serum samples were taken from 154 Dutch patients.
      As a reference method several biopsy specimens were taken from different gastric
      areas for histological analysis, bacterial culture and direct urease testing. The
      sensitivity, specificity, positive and negative predictive values of the
      Pyloriset IgG were calculated as compared to the reference method. RESULTS: Of
      154 patients 126 were found to be H. pylori positive (82%), 28 were H. pylori
      negative (18%). Using a cut-off value at a titre of 500 U/l (as advised by the
      manufacturer) we found a sensitivity, specificity, positive predictive value
      (PPV) and negative predictive value (NPV) of 81, 89, 97 and 51%, respectively.
      Lowering the cut-off value to 350 U/l and excluding patients aged above 70 years
      optimalized the performance of the Pyloriset IgG to a sensitivity, specificity,
      PPV and NPV of 92, 96, 99 and 72%, respectively. In the subgroup of 54 patients
      under the age of 45 years a sensitivity, specificity, PPV and NPV of 92, 100, 100
      and 82% was found. CONCLUSIONS: The Pyloriset IgG is a simple and accurate method
      for detecting H. pylori infection in dyspeptic Dutch patients. The performance of
      this assay is improved by lowering the cut-off value (test becomes predominantly
      more sensitive) and excluding older patients (test becomes predominantly more
      specific). Therefore serology might eventually replace endoscopy or breath tests
      in the detection of H. pylori infection, especially in the younger age groups.

PMID- 8569933
TI  - The Fitz-Hugh-Curtis syndrome, an unusual presentation.
AB  - The Fitz-Hugh-Curtis syndrome consists of adnexitis combined with perihepatitis.
      Prompt therapy with adequate antibiotics is required to prevent damaging
      complications. We describe a young woman with an unusual presentation, leading to
      initial confusion about the proper diagnosis.

PMID- 8569934
TI  - Extremely elevated body temperature: case report and review of classical heat
      stroke.
AB  - Classical heat stroke is a rare disease in moderate climates. We report a patient
      who demonstrated the classical triad of elevated body temperature, neurological
      disturbances, and anhidrosis. He developed rhabdomyolysis and acute renal
      failure. Eventually he died. Since manifestations of classical heat stroke appear
      to mimic an acute phase response, cytokines are thought to play an important role
      in its pathogenesis.

PMID- 8569935
TI  - Fever and rigors as sole symptoms of azathioprine hypersensitivity.
AB  - The case history of a haemodialysis patient with fever and rigors is presented.
      This diagnostic problem turned out to be a hypersensitivity reaction to
      azathioprine, with identical complaints recurring after a rechallenge with
      azathioprine, findings which resolved on discontinuation of this drug. The more
      extended indications for use of azathioprine warrant attention to the possibility
      of side-effects like drug fever.

PMID- 8569936
TI  - Metastatic staphylococcal lung abscess due to a cutaneous furuncle.
AB  - A seemingly trivial infection of the skin can lead to fulminant staphylococcal
      pneumonia and death. This case history describes the evolution of a fatal
      Staphylococcus aureus sepsis complicated by the development of multiple lung
      abscesses in a 17-year-old patient. A pre-existing cutaneous furuncle was the
      only identifiable cause. Early bacteraemic symptoms are described. Multiple
      cavitory lesions could be seen on a CAT-scan. The authors would like to stress
      the importance of early and adequate antibiotic treatment.

PMID- 8569937
TI  - Nocturnal hypoxaemia in patients with chronic obstructive pulmonary disease: who
      should be treated and how?

PMID- 8569938
TI  - Clinical decision theory: the threshold concept.

PMID- 8569939
TI  - New arguments in favour of cardioselective beta-blockers.

PMID- 8569940
TI  - Medical concerns and the national budget allocations.

PMID- 8569941
TI  - Arterial hypertension in uraemic patients treated with erythropoietin.

PMID- 8569942
TI  - Impaired polymorphonuclear neutrophil function in end-stage renal failure and its
      correction by continuous ambulatory peritoneal dialysis.
AB  - The polymorphonuclear neutrophil (PMN) function of 22 patients with end-stage
      renal failure (ESRF) was studied immediately before and 3 months after starting
      continuous ambulatory peritoneal dialysis (CAPD) and compared with a control
      group of healthy normal volunteers. The PMN functions studied were phagocytosis
      and killing of Staphylococcus epidermidis and respiratory burst activity. The
      results show that in the presence of normal pooled human serum PMN from patients
      with ESRF before CAPD treatment phagocytose bacteria normally, but have impaired
      killing. Before treatment, the PMN from patients with ESRF also showed an
      increase in both unstimulated and stimulated superoxide anion production.
      Abnormal PMN function was corrected by CAPD treatment, suggesting the involvement
      of a dialyzable toxin.

PMID- 8569943
TI  - Sleep apnea incidence in maintenance hemodialysis patients: influence of
      dialysate buffer.
AB  - A high prevalence of sleep disorders and sleep apnea syndrome in hemodialysis
      (HD) patients has been known for 10 years. Acetate, the buffer once most commonly
      used, favors intradialytic hypoxemia through hypoventilation and ventilation
      perfusion changes. The aim of the present study was to assess the influence of
      buffer, acetate or bicarbonate, on sleep and ventilation during the night
      subsequent to an afternoon (2-7 p.m.) dialysis session. Ten patients, 8 males and
      2 females, aged 35-71 years, dry weight 55-72 kg, on dialysis 15 h a week for 6
      67 months, were randomly assigned first to acetate or bicarbonate, then to the
      other mode of treatment. After a series of six sessions using the same buffer,
      polysomnographic recordings from 9.00 p.m. to 6.00 a.m. were obtained. Sex, age,
      weight, data of first dialysis, blood pressure and sleep disorder-related
      symptoms were not correlated with the sleep apnea syndrome. Prolonged or
      important oxygen desaturations were never observed. Central apnea occurred more
      frequently during the night following acetate dialysis: x = 33 (0-180) versus 3
      (0-15), p < 0.05. Obstructive apneas were not different. A defective modulation
      of ventilatory control after acetate HD might be held responsible for central
      apnea, which would constitute one more case for a widespread use of bicarbonate
      HD.

PMID- 8569944
TI  - Ultrasound diagnosis of suspected urinary tract obstruction using a stimulated
      diuresis test.
AB  - The aim of this study was to evaluate whether a stimulated diuresis test
      associated with ultrasound is able to differentiate pelvic dilation due to
      atonicity from pelviureteric junction obstruction (PUO). 42 patients (25 f, 17 m)
      with minimal or moderate renal pelvis dilation revealed by sonography were
      selected for the test. Three different measurements of the anteroposterior
      diameter (APD) of the renal pelvis were done at the renal hilus level, by using a
      transversal ultrasound scan: the first under spontaneous diuresis conditions, the
      second after hydration with 1.5 liters of water, and the third with a full
      bladder 15 min after intravenous injection of 20 mg frusemide. All the patients
      underwent pyelography. Baseline APD (bAPD) linearly correlated with the PAD both
      after hydration and frusemide (r = 0.89 and r = 0.84, respectively). A
      descriptive evaluation of the frequency distribution of the bAPD suggested the
      possibility that the data samples could belong to three populations with
      different underlying pathophysiological conditions. Correspondence analysis
      between bAPD distribution and PUO suggested that the best grouping of data was:
      group 1 (11 patients) bAPD < 13 mm, group 2 (14 patients) 13 > or = bAPD < or =
      20 mm, group 3 (17 patients) bAPD > 20 mm (likelihood ratio chi 2 46.36; d.f. =
      2). Standard intravenous pyelography showed an increase in pelvis size compatible
      with PUO in 2 patients from group 2 and in all patients from group 3.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8569945
TI  - Pharmacokinetic study of the low-molecular-weight heparin fraxiparin in patients
      with nephrotic syndrome.
AB  - We studied the pharmacokinetics of the low-molecular-weight heparin (LMWH)
      Fraxiparin in 6 patients with the nephrotic syndrome. Maximal plasma anti-Xa
      activity was obtained 5 h after a subcutaneous injection of 60 IU anti-Xa/kg.
      Anti-Xa activity was no longer detectable 24 h postinjection. These results are
      similar to those obtained with the same dosage in other clinical settings. The
      biological response to a daily subcutaneous injection of 60 IU anti-Xa/kg was
      studied for 8 days. No cumulative effect was observed. All the patients had an
      abnormal activation state of hemostasis mechanisms before treatment, as shown by
      high prothrombin fragment 1 + 2 and D-dimer levels, which were not decreased by
      Fraxiparin. It remains to be determined whether a higher dosage of LMWH might
      attenuate the hypercoagulability in these patients.

PMID- 8569946
TI  - Carbamylated hemoglobin in prerenal azotemia.
AB  - Carbamylated hemoglobin (Carb Hb) levels were measured in 16 patients with a
      documented transient rise in BUN due to prerenal azotemia, in whom BUN levels
      before and after the episode were normal. They were compared with 13 controls.
      Carb Hb was expressed as carbamyl valine concentrations, which were significantly
      higher in the patients (166 micrograms/g Hb) than in controls (95.3 micrograms/g
      Hb, p < 0.01). The mean maximum BUN level in the patients was 51.8 +/- 23.9
      mg/dl. There was a significant correlation between the product of mean BUN level
      times the number of days of BUN elevation, and the Carb Hb level (r = 0.5197; p <
      0.05). There was no correlation between Carb Hb and either mean BUN level or
      maximum BUN level. Elevated Carb Hb was seen after a minimum of 4 days' BUN
      elevation. Four patients had no elevation of Carb Hb despite elevated BUN levels.
      CONCLUSION: Carb Hb may be elevated after a minimum of 4 days' transient BUN
      elevation; Carb Hb is not useful in differentiating between mild acute renal
      failure and prerenal azotemia.

PMID- 8569947
TI  - Interferon treatment of chronic active hepatitis C in patients with end-stage
      chronic renal failure.
AB  - Alpha interferon has been shown to be effective in the treatment of chronic
      hepatitis C virus infection. We studied the efficacy of alpha 2a-interferon in
      chronic active hepatitis C patients with end-stage chronic renal failure (CRF).
      Thirteen patients with CRF and 12 patients with a normal renal function were
      included in the study. The patients received interferon 3 million units three
      times a week subcutaneously for 6 months. All patients with CRF and 6 patients
      without CRF had a complete response, defined as a decline in serum alanine
      aminotransferase levels to the normal range. One patient had a decrease in
      alanine aminotransferase of more than 50%, and 5 patients were nonresponders. A
      relapse was observed in 4 patients with and in 4 without CRF. Three patients had
      renal transplantation, and the alanine aminotransferase levels were normal after
      12-14 months. This preliminary study shows that interferon is effective in the
      treatment of patients with chronic hepatitis C and CRF.

PMID- 8569948
TI  - Purification and analysis of plasmatic components of middle molecular weight in
      patients with uremic syndrome.
AB  - Many hormonal, metabolic and enzymatic alterations have been described in
      patients with chronic renal failure (CRF) after prolonged hemodialysis treatment.
      This toxicity has been associated with the accumulation of middle molecular
      weight components, called 'middle molecules', in their blood. To investigate the
      chemical nature of these molecules, 20 CRF patients were studied and compared
      with 10 control subjects. Sera from these individuals were treated with molecular
      exclusion chromatography, the components of high molecular weight were eliminated
      from the elution peaks, and the remainder was then concentrated by
      lyophilization. The zones of greatest concentration were fractioned by ionic
      exchange chromatography and by HPLC in reverse phase. Infrared spectroscopy was
      also performed on the most relevant zones, as well as SDS/PAGE. Finally, the
      amino acid sequence of a peak presenting the best conditions was analyzed. The
      results indicate that the majority of the compounds isolated are peptides, amino
      acids or amino alcohols, and that many of these 'middle molecules' are joined to
      trace metals.

PMID- 8569949
TI  - Role for Doppler ultrasound in the assessment of renal circulation: effects of
      dopamine and dobutamine on renal hemodynamics in humans.
AB  - To examine the utility of Doppler ultrasound in assessing renal hemodynamics, we
      investigated the effects of dopamine and dobutamine on renal blood flow using
      Doppler ultrasound technique and conventional clearance tests in 7 healthy
      volunteers. After visualization of arterial blood flow in the right renal hilus
      by two-dimensional color flow mapping, the phasic blood flow velocity in the
      vessel was obtained by a pulsed Doppler method. Intravenous infusion of dopamine
      at a low dose increased the velocity and decreased the waveform pulsatility of
      renal artery blood flow without causing any significant changes in blood
      pressure, heart rate, or cardiac index. In contrast, dobutamine infusion
      increased the peak systolic velocity in a dose-dependent manner, but did not
      increase the mean velocity or decrease the waveform pulsatility. Percent changes
      of renal blood flow during infusions of both agents correlated well with those of
      the mean velocity. Furthermore, the degrees of changes of the waveform
      pulsatility were consistent with those of renal vascular resistance obtained from
      clearance tests and blood pressure. Our results suggest that mean velocity
      reflects renal blood flow and the pulsatility of blood flow waveform represents
      renal vascular resistance. We conclude that the effects of vasoactive agents on
      renal blood flow and renal vascular resistance can be estimated noninvasively,
      directly, and repeatedly using Doppler ultrasound.

PMID- 8569950
TI  - Antioxidant enzymes activity in polymorphonuclear leukocytes in chronic renal
      failure.
AB  - In the present study, activity of polymorphonuclear leukocyte (PMNL)
      intracellular antioxidant enzymes, i.e. catalase, superoxide dismutase (SOD) and
      glutathione peroxidase (GPX), was assessed in CRF patients on hemodialysis (HD),
      or continuous ambulatory peritoneal dialysis (CAPD) and in healthy controls. The
      activity of SOD and GPX was reduced in HD and in CAPD (SOD: by 34.2 and 42%,
      respectively, and GPX 66 vs. 42%, respectively, taking the activity in normal
      controls as 100%). Catalase activity, on the other hand, was significantly
      augmented (298 and 175%, respectively) as compared to the healthy controls. This
      impairment in antioxidant enzymes activity, involved in the respiratory burst and
      phagocytosis, may contribute to the understanding of the reduced bactericidal
      ability of PMNL activity found in these patients.

PMID- 8569951
TI  - Influence of HLA-DR phenotype on tumor necrosis factor-alpha production in renal
      transplant recipients.
AB  - In healthy subjects, previous studies have demonstrated a great interindividual
      variability in the ability for tumor necrosis factor-alpha (TNF-alpha)
      production. The gene for TNF-alpha is closely linked to and located in the major
      histocompatibility complex (MHC) and it has been suggested that these
      interindividual differences may be HLA related. Since TNF-alpha is likely to be
      an important mediator in renal allograft rejection, we investigated the role of
      HLA antigens on TNF-alpha production rates by peripheral blood mononuclear cells
      (PBMC) from renal transplant recipients during stable graft function. HLA-DR2
      positive recipients showed significantly lower spontaneous TNF-alpha production
      than DR2-negative patients (p < 0.001). Upon stimulation with OKT3, HLA-DR2
      positive patients also showed significantly lower TNF-alpha production than DR2
      negative subjects (p < 0.001). HLA-DR3-positive recipients, however, showed
      significantly higher spontaneous TNF-alpha production than DR3-negative
      individuals (p < 0.05). These results suggest that differences in TNF-alpha
      production, both spontaneous and induced, may be due to the expression of certain
      DR allotypes.

PMID- 8569952
TI  - Renal haemodynamic responses to adenosine in acute renal failure.
AB  - Renal vascular reactivity was studied in rats with acute renal failure (ARF) to
      investigate whether changes in sensitivity to the renal haemodynamic effects of
      adenosine can explain why adenosine plays a significant role in some but not all
      forms of ARF. Experiments involved rats with glycerol-induced ARF in which
      adenosine antagonists have been shown previously to have beneficial effects and
      rats with HgCl2-induced ARF which was not ameliorated by treatment with the
      selective A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.1 mg/kg). Close
      renal arterial injections of adenosine (0.1-10 micrograms) or noradrenaline
      (0.003-0.1 microgram) produced falls in renal blood flow in rats with HgCl2
      induced ARF which were not statistically different from controls. Adenosine
      evoked falls in renal blood flow in rats with glycerol-induced ARF which were
      significantly greater 16 and 48 h, but not 30 min after glycerol injection. The
      enhanced responsiveness to adenosine's renal constrictor effects was most
      pronounced 48 h following glycerol injection when, for example, a dose of 10
      micrograms produced a fall of 60 +/- (SEM) 5% (n = 8) in renal blood flow in
      comparison to a fall of 27 +/- 5% (n = 8) in controls. By contrast to the renal
      vascular response to adenosine, the falls in renal blood flow induced by
      noradrenaline in rats 48 h following glycerol injection were not statistically
      different from the decreases in renal blood flow recorded in control
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8569953
TI  - Erythropoietin modified the cardiac action of ouabain in chronically anaemic
      uraemic rats.
AB  - The results of the studies reported here demonstrate the cardiac non
      haematopoietic effect of erythropoietin, providing a new physiological function
      of the hormone. We demonstrate that myocardium from rat with chronic renal
      failure (CRF) showed an abnormal response to ouabain associated with an
      inhibition of cardiac Na+/K+/ATPase activity and with a decrease in the high
      affinity 3H-ouabain binding sites. The extent to which both actions were improved
      with the recombinant human erythropoietin (rHuEpo) treatment suggests that the
      lack of the hormone is responsible for this phenomenon. The fact is that neither
      contractile nor enzymatic action of rHuEpo was accompanied with the improvement
      of the functional renal and haematologic parameters, indicating a primary effect
      on myocardial contractile function of rHuEpo, independent of the anaemic and
      uraemic state of the animal. The reason why erythropoietin is able to modulate
      directly the cardiac Na+/K+ pump makes it possible to conclude that the lack of
      erythropoietin in CRF may be at least in part responsible for the inhibition of
      cardiac enzymes, altering the contractile behaviour of the heart.

PMID- 8569954
TI  - Heparan sulfate stimulates extracellular matrix protein synthesis by mesangial
      cells in culture.
AB  - Heparan sulfate, a glycosaminoglycan which is a component of the glomerular
      basement membrane and the mesangial matrix, has been demonstrated to inhibit
      mesangial cell growth. The present studies investigated the effects of heparan
      sulfate on extracellular matrix protein synthesis by cultured rat mesangial
      cells. Mesangial cells were metabolically labeled with 35S-methionine and
      specific extracellular matrix proteins were immunoprecipitated from supernatant
      and cellular fractions. The following extracellular proteins were assayed: type I
      collagen, type IV collagen, type V collagen, laminin and fibronectin. Western
      blotting was performed to demonstrate the specificity of the immunoprecipitates.
      Heparan sulfate decreased cell number by 23.5%, p < 0.05, while chondroitin
      sulfate, another glycosaminoglycan, increased cell number by 11.5%, p < 0.05.
      Heparan sulfate significantly increased type V collagen and laminin in the
      cellular material and significantly increased laminin and fibronectin in the
      supernatant material. Chondroitin sulfate had no effect on matrix protein
      synthesis. Thus, heparan sulfate has effects on both mesangial cell growth and
      synthesis of matrix proteins and alterations in heparan sulfate may play a role
      in the development of glomerulosclerosis.

PMID- 8569955
TI  - Effect of NG-nitro-L-arginine methyl ester on nephrotoxicity induced by
      gentamicin in rats.
AB  - The present experiments were designed to assess the effect of inhibiting NO
      synthesis on the renal failure induced in rats by treatment with high doses of
      gentamicin. Eighteen Wistar rats were given gentamicin 100 mg/kg body weight/day
      for 5 days, whereas another 18 rats were used as control. Half of the gentamicin
      treated rats and half of the controls also received the specific inhibitor of NO
      synthesis, NG-nitro-L-arginine methyl ester (L-NAME), 0.05 mg/ml in the drinking
      water for 5 days. Arterial pressure and renal function were measured on the 5th
      day of the study. In the animals treated with L-NAME, arterial pressure was
      higher than in untreated rats, thus suggesting that the treatment was effective
      in inhibiting NO synthesis. Rats that received L-NAME and gentamicin, showed
      higher plasma creatinine levels and higher score of renal damage, as well as
      lower Na+ and K+ excretion and creatinine clearance than rats that received
      gentamicin alone. These data showing that NO inhibition aggravates gentamicin
      induced renal failure, suggest that endogenously released NO plays a protective
      role in gentamicin nephrotoxicity.

PMID- 8569956
TI  - Prevention of glomerular hypertrophy and glomerulosclerosis in Milan normotensive
      rats by low-protein diet, but not by low-dose captopril treatment.
AB  - Milan normotensive rats, which spontaneously develop marked proteinuria (PU) and
      glomerulosclerosis (GS), were either kept on a normal-protein diet, a normal
      protein diet with additional low-dose captopril (CAP), which did not affect blood
      pressure, or on a low-protein diet. After 8 months PU (79 +/- 25 mg/day) GS (3 +/
      2%) and total glomerular volume (TGV; 27.9 +/- 2.9 mm3/kidney) were
      significantly lower (p < 0.05) in the low-protein diet group than in both the
      normal-protein group (PU 583 +/- 210 mg/day, GS 12 +/- 5%, TGV 34.6 +/- 8
      mm3/kidney) and the low-CAP group (PU 611 +/- 224 mg/day, GS 16 +/- 6%, TGV 41.8
      +/- 8.6 mm3/kidney). In conclusion, the development of glomerular hypertrophy and
      GS in Milan normotensive rats was reduced by the low-protein diet, but not by low
      CAP treatment.

PMID- 8569957
TI  - Clinicopathological features of hepatitis C virus antibody negative fatal chronic
      hepatitis C after renal transplantation.
AB  - Clinical course and serial liver histology of a patient who developed fatal
      chronic active hepatitis C after renal transplantation are presented. This
      patient developed persistently deranged liver biochemistry 3 months after
      transplantation, despite normal liver enzyme values during the preceding 3 years
      on hemodialysis. In addition to increased parenchymal enzyme concentrations, the
      levels of ductal enzymes were also markedly elevated, with peak levels of alanine
      aminotransferase and gamma-glutamyl transpeptidase 7 and 100 times, respectively,
      the normal upper limit. The patient was persistently seronegative for hepatitis C
      virus (HCV) antibodies, but positive for HCV RNA. Treatment with alpha-interferon
      for 6 months, initiated after the development of early cirrhosis, resulted in no
      improvement, and the patient died from liver failure 36 months after renal
      transplantation. Serial liver histology, examined four times from 11 months to 36
      months after transplantation, showed progressive deterioration from chronic
      active hepatitis to cirrhosis. This patient illustrates the uncommon complication
      of rapidly progressive and ultimately fatal liver disease due to HCV infection
      after renal transplantation. Early recognition with anti-HCV and HCV RNA assays
      as well as histologic assessment are crucial for the identification of patients
      with a poor prognosis who might benefit from therapeutic intervention before
      irreversible liver damage.

PMID- 8569958
TI  - Studies in a hemodialysis patient indicating that calcitriol may have a direct
      suppressive effect on bone.
AB  - Calcitriol putatively suppresses bone activity by decreasing parathyroid hormone
      (PTH) levels. Results of studies in a 52-year-old female maintenance hemodialysis
      patient suggest that calcitriol may also have a direct suppressive effect on
      bone. The PTH-calcium relationship was evaluated through the use of low (1 mEq/l)
      and high (4 mEq/l) calcium hemodialyses that were performed before the initiation
      of calcitriol treatment, at the end of 6 weeks of thrice-weekly intravenous
      calcitriol administration, and 6 weeks after the discontinuation of calcitriol.
      During the low-calcium dialysis, serum calcium decreased more rapidly and to a
      greater magnitude after calcitriol treatment despite no appreciable difference in
      basal and maximally stimulated PTH levels; during the high-calcium dialysis,
      calcitriol treatment resulted in a more rapid increase in serum calcium despite
      no appreciable difference in basal and maximally suppressed PTH levels.
      Discontinuation of calcitriol resulted in responses to the low and high calcium
      dialyses that were similar to those observed before calcitriol treatment. In
      conclusion, the results suggest that calcitriol may have a direct suppressive
      effect on bone that is independent of PTH.

PMID- 8569959
TI  - Renal histology in a patient with nephrogenic diabetes insipidus.

PMID- 8569960
TI  - Severe unresponsive thrombocytopenia in a transplantated patient with chronic
      Werlhof's disease: correction after splenectomy.

PMID- 8569961
TI  - Hepatitis C virus infection contracted just before kidney transplantation.

PMID- 8569962
TI  - Severe reduction of renal function in hypertensives and/or diabetics induced by
      angiotensin-converting enzyme inhibitors.

PMID- 8569963
TI  - Autosomal dominant polycystic kidney disease and mesangioproliferative
      glomerulonephritis.

PMID- 8569964
TI  - A case of methotrexate-induced acute renal failure successfully treated with
      plasma perfusion and sequential hemodialysis.

PMID- 8569965
TI  - Acute renal failure associated with rhinosinuso-orbital mucormycosis infection in
      a patient with diabetic nephropathy.

PMID- 8569966
TI  - Does erythropoietin production after renal transplantation depend on the type of
      immunosuppression?

PMID- 8569967
TI  - Plasma-ionized magnesium concentration in a child with magnesium-losing
      tubulopathy.

PMID- 8569968
TI  - Effect of (D)-penicillamine on oxalate production.

PMID- 8569969
TI  - Absence of macroscopic hematuria in a case of IgA nephropathy and Graves' disease
      with acute renal failure.

PMID- 8569970
TI  - von Recklinghausen's disease associated with angiodysplasia of colon and end
      stage renal disease.

PMID- 8569971
TI  - Outcome of renal transplantation from foreign unrelated living donors in Turkey.

PMID- 8569972
TI  - Increased risk of stable renal allografts after changing from ciclosporin to
      azathioprine.

PMID- 8569973
TI  - Prognosis of autosomal dominant polycystic kidney disease.

PMID- 8569974
TI  - Hepatitis C virus infection and the renal allograft recipient.

PMID- 8569975
TI  - 1-alpha-Hydroxyvitamin D3 derivatives in the treatment of renal bone diseases:
      justification and optimal modalities of administration.
AB  - The use of 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] derivatives in a uremic
      patient is justified only in the treatment of hyperparathyroidism (i.e. when
      plasma intact parathyroid hormone - PTH - levels are above five or three times
      the upper limit of normal according to whether the patient is on continuous
      ambulatory peritoneal dialysis or on hemodialysis and between 0.5-1.5, 1-2 and 2
      3 times the upper limit of normal for a creatinine clearance of, respectively,
      30, between 30 and 10, or below 10 ml/min/1.73 m2). The following prerequisites
      have however to be satisfied: (1) a good vitamin D3 repletion should be secured
      by plasma 25(OH(D) levels of 20-30 ng/ml (if necessary by administration of
      native vitamin D or 25(OH)D3), and (2) phosphate retention (which is aggravated
      by the increased phosphate intestinal absorption induced by the 1 alpha (OH)D
      derivatives) and the consequent possible hyperphosphatemia should be prevented or
      corrected by the oral administration of alkaline salts of calcium given before
      the meals as phosphate binders without inducing hypercalcemia. These
      prerequisites explain the narrow therapeutical margin of 1 alpha (OH)D3
      derivatives in uremic patients before dialysis (more so in the adult than in the
      child) and the possible broadening of this margin in the patients on dialysis by
      the use of low dialysate calcium concentrations (1.25-1.00 mmol/l) in order to
      prevent hypercalcemia by inducing a negative perdialytic calcium balance. Once
      hyperphosphatemia is prevented by oral calcium, 1 alpha (OH)D3 derivatives have
      the advantage to suppress the transcription of the prepro PTH gene by a mechanism
      independent of an increase in plasma calcium. Controlled randomized trials have
      not confirmed the claimed advantage in efficacy and safety of the parenteral
      versus the oral route nor of the intermittent versus the daily mode of their
      administration. The advantages of using the so called 'nonhypercalcemic
      hyperphosphatemic' vitamin D3 derivatives in combination with oral calcium over 1
      alpha(OH)D3 derivatives in the treatment of uremic hyperparathyroidism are still
      waiting for clinical demonstration. Vitamin D derivatives have no place in the
      treatment of aluminic bone diseases which necessitate long term deferoxamine
      treatment and prevention of aluminum exposure by the dialysate and the phosphate
      binders. They are not indicated in the treatment of 'idiopathic' adynamic bone
      disease which is due to uremia per se combined with an excessive PTH suppression
      for the degree of renal failure. This low bone turnover pattern is associated
      with an increased risk of hypercalcemia and hyperphosphatemia and necessitates
      only a stimulation of PTH secretion by inducing a negative calcium balance with a
      lower dialysate calcium concentration or simply by discontinuing the oral calcium
      supplement in the uremic patient not yet dialyzed. In rare cases this pattern is
      due to a granulomatosis and is corrected by prednisone.

PMID- 8569976
TI  - Effect of parathyroidectomy on thyrotropic and lactotropic function in patients
      with renal osteopathy.
AB  - To test the effect of parathyroidectomy on thyrotropic and lactotropic function,
      a thyrotropin-releasing hormone (TRH) test was performed before and between the
      2nd and 3rd month after operation in 13 haemodialysed patients with secondary
      hyperparathyroidism. The thyrotropin response to TRH was higher in the
      postoperative period as compared with the values before the operation (p < 0.01).
      The prolactin response to TRH did not differ from the values before the
      operation. No correlations between thyrotropin response and serum parathyroid
      hormone (PTH), ionised calcium and haemoglobin or haematocrit were found. The
      lower sensitivity of the thyrotropic system to TRH in patients with renal
      osteopathy is not dependent on serum PTH or calcium.

PMID- 8569977
TI  - Increased plasma endothelin concentration in atherosclerotic renovascular
      hypertension.
AB  - The aim was to investigate circulating levels of immunoreactive endothelin (ir
      ET) in atherosclerotic renovascular hypertension (RVH), and to assess the role of
      the kidneys in its overall plasma concentration. We studied 16 hypertensive
      patients with renal artery stenosis evidenced by angiography and admitted to
      hospital for the diagnostic evaluation of RVH by renal vein plasma renin activity
      (PRA) determinations. The right femoral vein was catheterized to simultaneously
      measure PRA and ir-ET in both renal veins and inferior vena cava below the origin
      of the renal veins. RVH was present in 9 patients as indicated by diagnostic PRA
      renal vein ratios and the remaining 7 patients were considered to have essential
      hypertension (EH). Patients with RVH showed a marked increase in systemic plasma
      ir-ET concentration (10.3 +/- 0.9 pg/ml). Despite a significant increase of PRA
      in the vein of the ischemic (IK) versus the contralateral (CK) kidney in patients
      with RVH, no significant differences in ir-ET concentration were observed between
      both kidneys. These results indicate that patients with RVH have increased
      circulating levels of ir-ET. However, the higher systemic plasma ir-ET do not
      arise from the renal circulation, since plasma ir-ET is significantly higher in
      systemic circulation than in renal veins.

PMID- 8569978
TI  - Heme synthesis in chronic renal failure: the effects of hemodialysis, peritoneal
      dialysis and erythropoietin treatment.
AB  - Increased plasma porphyrins have been described in patients with chronic renal
      failure (CRF). We measured plasma levels of porphyrins and the activity in
      erythrocytes of porphobilinogen deaminase (PBG-D), one of the key enzymes in heme
      biosynthesis, in CRF patients not yet on dialysis and in patients on intermittent
      hemodialysis (IHD) or chronic ambulatory peritoneal dialysis (CAPD), some of whom
      were being treated with recombinant human erythropoietin (rHuEPO). In addition,
      the amount of immuno-detectable PBG-D (Ig PBG-D) per 100 units standard PBG-D
      activity (Ig PBG-D/100 U) and the total amount of Ig PBG-D, using polyclonal
      antibodies, were determined in erythrocytes of all patients and controls to
      detect changes in biodegradation of this enzyme. Plasma porphyrins were increased
      in CRF patients not yet on dialysis and even higher in both patient groups on
      dialysis compared with controls. Plasma porphyrins were higher in patients on IHD
      than in patients on CAPD. The activity of PBG-D was increased and Ig PBG-D/100 U
      was decreased in patients on IHD compared with CRF patients not yet on dialysis
      and patients on CAPD. Reticulocyte counts were also greater in patients on IHD
      than in CRF patients not yet on dialysis and patients on CAPD. Ig PBG-D was
      increased in both groups of patients on dialysis and treated with rHuEPO compared
      with patients not treated with rHuEPO. IN CONCLUSION: (1) in patients on IHD, an
      increased production of porphyrins is, at least partly, caused by an increased
      PBG-D activity, and (2) an increased PBG-D activity and a decrease in Ig PBG
      D/100 U in patients on IHD could be explained by the presence of a (relatively)
      young erythroid cell population in which a larger part of PBG-D has not yet been
      degraded.

PMID- 8569979
TI  - Renal expression of interleukin-2 receptor mRNA in patients with crescentic
      glomerulonephritis.
AB  - We studied paraffin sections of renal biopsies from 7 patients with crescentic
      glomerulonephritis (CGN) by in situ hybridisation, to detect sites of interleukin
      2 receptor (IL-2R) mRNA expression. Frozen sections from a further patient with
      CGN were studied by immunohistochemistry with a monoclonal antibody to CD25, to
      detect IL-2R protein. Positive control sections were taken from biopsies of acute
      cellular renal transplant rejection and negative controls from biopsies of
      membranous glomerulonephritis. No autoradiographic signal was detected in
      negative controls. IL-2R mRNA expression was seen in rejected transplants and in
      sections from 4 to 7 patients with CGN. Expression was seen in cortical
      interstitial cells, renal tubular epithelial cells, cells within glomerular
      crescents and in one glomerulus at the margin of Bowman's capsule. Tubular cell
      expression of IL-2R protein was confirmed by immunohistochemistry. We have
      confirmed that IL-2R mRNA expression occurs locally within the kidneys in CGN and
      have identified expression in tubular epithelial cells. The results suggest that
      local activation of immunocompetent cells occurs in the kidney and may be of
      significance in the pathogenesis of CGN.

PMID- 8569980
TI  - Plasma cytokine levels in hemolytic uremic syndrome.
AB  - The cytokines tumor necrosis factor-alpha (TNF-alpha) and its soluble TNF
      receptors 55 and 75 (sTNFR55, sTNFR75), interleukin-1 beta (IL-1BETA) and
      interleukin-6 (IL-6) were measured in plasma from 13 patients with the hemolytic
      uremic syndrome (HUS) on admission. No significant changes in the plasma levels
      of TNF-alpha and IL-1beta were detected in the HUS patients as compared to the
      plasma levels of the control groups. Levels of IL-6 were significantly elevated
      in the plasma of those HUS patients who had external manifestations, consisting
      of seizures, loss of consciousness, coma and pancreatic necrosis. Although the
      exact function of IL-6 in the plasma of HUS patients is still unknown and the
      group of HUS patients is small, plasma IL-6 is associated with the the severity
      and outcome of the disease. Plasma levels of sTNR55 and sTNFR75 were
      significantly elevated in all HUS patients compared to the healthy controls, but
      they were also elevated in the children with chronic renal failure. This
      indicates that elevated levels of circulating sTNFR should be carefully
      interpreted when kidney failure exists.

PMID- 8569981
TI  - Role of peritoneal loss of albumin in the hypoalbuminemia of continuous
      ambulatory peritoneal dialysis patients: relationship to peritoneal transport of
      solutes.
AB  - The effects of peritoneal albumin loss and the consequences of heterogeneous
      peritoneal solute transport on serum albumin levels were investigated in 25 adult
      patients on standard continuous ambulatory peritoneal dialysis (0-58 months). The
      patients were divided into three groups according to their albumin concentrations
      (g/l/l.73 m2) in 8-hour overnight effluents: group 1 ( < 0.6, n = 5), group 2
      (0.6-1.1; n = 14), and group 3 ( > 1.1;n= 6). Significant differences (mean +/-
      SD) were observed in serum albumin levels (4.4 +/- 0.2, 3.7 +/- 0.3, and 3.1 +/-
      0.5 g/dl, respectively) and in net ultrafiltration (0.37 +/- 0.13, 0.19 +/- 0.21,
      and -0.06 +/- 0.20 liters/8 h/1.73m2, respectively). The serum albumin levels
      were strongly correlated with 8-hour peritoneal mass transfer, clearance of
      albumin, 8-hour effluent concentrations of protein and glucose, and
      ultrafiltration rate. Moreover, the serum albumin levels showed significant
      negative correlations with dialysate-to-serum ratios of small solutes (urea,
      creatinine, and uric acid) and macromolecules (IgG, IgA, and IgM) estimated from
      8-, 4-, and 1-hour dwell times. In addition, an overnight dialysate glucose-to
      protein ratio < 1.0 was highly predictive of low serum albumin levels ( < or =
      3.5 g/dl) and poor ultrafiltration. From the results of this study we conclude
      that peritoneal loss of albumin as well as peritoneal transport of other solutes
      of wide size ('permeability') contribute to the low serum albumin levels during
      continuous ambulatory peritoneal dialysis, especially in patients with a high
      peritoneal permeability.

PMID- 8569982
TI  - Sequential therapy for diffuse proliferative and membranous lupus nephritis:
      cyclophosphamide and prednisolone followed by azathioprine and prednisolone.
AB  - A retrospective single-center cohort study was conducted on 35 patients with
      diffuse proliferative (WHO type IV) and/or membranous (type V) lupus nephritis
      (22 with type IV, 6 with type V, and 7 with type IV plus V) who had been treated
      with a sequential regimen comprising prednisolone and cyclophosphamide during
      active disease, followed by low-dose prednisolone and azathioprine maintenance.
      The follow-up period was 33.2 +/- 4.5 months. At presentation, 32 (91.4%)
      patients were nephrotic, and an abnormal serum creatinine level was noted in 14
      (48.3%) patients with type IV changes. Cyclophosphamide was given for 26.8 +/-
      2.8 weeks. 33 (94.3%) patients achieved complete or partial renal remissions:
      77.3 and 22.7% of the type IV patients, 16.7 and 66.6% of the type V patients,
      and 14.3 and 71.4% of the type IV plus V patients, respectively (p < 0.0001 for
      type IV versus type V and for type IV versus type IV plus V). The duration of
      therapy before renal remissions and normalization of C3 were attained was similar
      among the three groups of patients. Disease relapse occurred in 4 (18.2%) of 22
      IV patients and in 1 of the 5 type V patients in remission. Mortality was not
      observed, and none of the patients had an increase in serum creatinine level to
      double the baseline value. Adverse effects related to therapy included: hair loss
      (42.9%), transient amenorrhea (53.6%), leukopenia (11.4%), febrile episodes
      (14.3%), and herpes zoster(28.6%). We conclude that sequential use of
      prednisolone and cyclophosphamide followed by low-dose prednisolone and
      azathioprine can achieve favorable therapeutic results in the majority of
      patients with diffuse proliferative and/or membranous lupus nephritis, without
      excessive toxicities.

PMID- 8569983
TI  - Urinary excretion of free cystine and the tiopronin-cysteine-mixed disulfide
      during long term tiopronin treatment of cystinuria.
AB  - We report the results of a biochemical evaluation of long-term treatment of
      cystinuria with the SH compound tiopronin (2-mercaptopropionylglycine). The
      effects of tiopronin were studied by monitoring the urinary excretion of free
      cysteine and the mixed disulfide between tiopronin and cysteine. Thirty-one
      patients with homozygous cystinuria were treated with tiopronin for 0.4-12 years
      (mean 7.8 years). The urinary concentration of free cysteine was used to adjust
      the tiopronin dose. In 28 of the 31 patients a mean urinary cystine concentration
      of less than 1,200 mumol/1(288 mg/l) was achieved with the final dose. The final
      daily doses of tiopronin ranged from 250 mg (1.5 mmol) to 3,000 mg (18.4 mmol;
      mean 1,540 mg; 9.4 mmol). In a majority of the patients the treatment reduced the
      24-hour urinary free cystine excretion effectively, on average by 0.61 mumol
      (0.15 mg)/mg of tiopronin administered. No changes in the efficacy of tiopronin
      over time were observed, and the frequency of adverse effects was acceptable. To
      evaluate the effects of tiopronin on the metabolism of cystine we calculated the
      total urinary excretion of cystine as the sum of free cystine and the amount of
      cystine corresponding to the cysteine content of the tiopronin-cysteine
      disulfide. At low doses of tiopronin there was an increase in urinary excretion
      of the mixed disulfide as well as of total cystine. Monitoring urinary cystine
      concentration is necessary to achieve adequate individualized doses of tiopronin.
      Assessment of the mixed tiopronin-cysteine disulfide and the urinary excretion of
      total cystine shows that tiopronin may interfere with cystine metabolism in a
      more complex way than through a simple disulfide exchange reaction with urinary
      cystine.

PMID- 8569984
TI  - Reduced glutathione for the treatment of anemia during hemodialysis: a
      preliminary communication.
AB  - In 4 chronic hemodialysis patients we have tested whether the administration of
      reduced glutathione (GSH; Glutamed, Boehringer Mannheim Italia; 1,200 mg i.v.) at
      the end of each hemodialytic session during 90 days could minimize oxidative
      damage to the red blood cells (RBC) and reduce the recombinant human
      erythropoietin requirements. Treatment with GSH was followed by an increase in
      RBC GSH content (n = 3), a normalization of the ascorbine cyanide test (n = 4),
      an increase in RBC survival (n = 3), and a reduction in 2 patients of the
      erythropoietin need (41 and 26%, respectively, after 3 months of therapy). When
      the GSH supplements were terminated, we noticed after 3 months a re-establishment
      of the baseline values. On the other hand, malonyldialdehyde, RBC deformability,
      and RBC splenic pool were abnormal before and remain abnormal during the test
      period. Since no adverse reactions were noticed, these findings seem to indicate
      the GSH could ameliorate the intraerythrocytic oxidative defense and could be as
      useful drug in the treatment of anemia in patients affected by chronic renal
      failure.

PMID- 8569985
TI  - Calcitriol pulse therapy for severe hyperparathyroidism or calcium salts as
      phosphate binders in renal dialysis patients?
AB  - The concurrent use of calcitriol (CAL) pulse therapy to reduce parathyroid
      hormone (PTH) secretion and of calcium (Ca) salts as the most appropriate
      phosphate binders was evaluated for over 1 year in a group of 14 patients with
      good divalent ion control on CaCO3 therapy but with increasing levels of serum
      intact PTH. CAL pulse therapy was effective and safe in only 2 patients; in the
      remaining subjects it resulted in hypercalcemia and/or hyperphosphatemia, not
      reversed by adjusting the dialysate Ca concentration and or CaCO3 dose, and had
      to be stopped. Therefore, CAL pulse therapy does not seem to be compatible with
      Ca salts which, in our opinion, deserve priority in the therapy of renal dialysis
      patients.

PMID- 8569986
TI  - Severe renal hypouricemia secondary to hyperbilirubinemia.
AB  - A 64-year-old man with alcoholic liver cirrhosis had a progressive decrease in
      the serum uric acid (UA) until it became undetectable, an increase renal UA
      clearance, mild glycosuria with normal serum glucose and a decrease in the
      tubular reabsorption of phosphate in association with cholestasis secondary to a
      gallbladder carcinoma. All these abnormalities returned to normal when the serum
      bilirubin levels decreased following surgical treatment. This clinical
      observation suggests that the reversible renal tubular transport defect was
      secondary to high levels of serum bilirubin.

PMID- 8569987
TI  - Low serum TSH levels and negative TRH test in dialysis patients.

PMID- 8569988
TI  - Angiotensin-converting enzyme (ACE) polymorphisms, angiotensin II, ACE inhibitors
      and glomerulosclerosis--a hypothesis.

PMID- 8569989
TI  - Re: Rapidly progressive glomerulonephritis.

PMID- 8569990
TI  - The beginning of repeated hemodialysis treatment enhances some platelet functions
      in uremic patients.

PMID- 8569991
TI  - Nosocomial transmission of hepatitis C virus to hemodialysis patients: molecular
      epidemiology by polymerase chain reaction.

PMID- 8569992
TI  - Exposure of dialysis care staff to patient blood: it is more probable in
      hepatitis C virus-positive patients.

PMID- 8569993
TI  - Rapidly progressive glomerulonephritis in association with Henoch-Schonlein
      purpura in a patient with advanced liver cirrhosis.

PMID- 8569994
TI  - Frequency of renal amyloidosis secondary to tuberculosis.

PMID- 8569995
TI  - Pancytopenia due to Paludrine (proguanil hydrochloride)

PMID- 8569996
TI  - Effect of atrial natriuretic factor on vasopressin-stimulated cyclic AMP
      accumulation in papillary collecting tubule.

PMID- 8569997
TI  - Aluminum urinary excretion in patients with chronic renal failure in treatment
      with conservative conventional therapy and with ketoanalogs: research on fasting
      patients and after a pharmacological load.

PMID- 8569998
TI  - Gompertzian analysis of amyotrophic lateral sclerosis mortality in Italy, 1957
      1987; application to birth cohorts.
AB  - During the last 3 decades, the mortality rates of amyotrophic lateral sclerosis
      (ALS) markedly increased in various countries, including Italy. This finding has
      been attributed to factors such as better case ascertainment or changes in the
      demographic structure of the population, or to unknown environmental factors. The
      longitudinal Gompertzian analysis represents an alternative way to evaluate this
      phenomenon. Mortality from ALS in Italy in the last three decades fits in well
      with the Gompertz model in both sexes, and also with specific mortality of
      different birth cohorts. The 'environmental' factor R0 showed a decreasing trend
      in the most recent birth cohorts. Therefore, according to this model, the
      increase in ALS mortality during the last few decades may be due to the increased
      strength in competing for mortality of ALS compared to other diseases.

PMID- 8569999
TI  - A population-based study of neonatal seizures in Fayette County, Kentucky:
      comparison of ascertainment using different health data systems.
AB  - Based on a population-based, retrospective cohort study of neonatal seizures in
      Fayette County, Kentucky, from 1985 to 1989, estimates of neonatal seizure risk
      were calculated from computerized databases including hospital medical records,
      birth certificates, and death certificates. Computerized tabulations of hospital
      discharge diagnoses identified 97% of cases with a positive predictive value of
      75%. Birth certificates had poor sensitivity for neonatal seizures overall (37%),
      but identified 67% of infants who seized on the first day of life. However,
      careless completion of the birth certificate produced a high number of false
      positives. Death certificates identified no infants with neonatal seizures.

PMID- 8570000
TI  - Epidemiology of multiple sclerosis in US veterans. 6. Population ancestry and
      surname ethnicity as risk factors for multiple sclerosis.
AB  - Previously, we studied the effect of population ancestry on the risk of multiple
      sclerosis (MS) in US veterans of World War II, comparing by state 1980 US census
      ancestry data with MS case/control ratios. Here, the joint effects of population
      ancestry and surname-derived ethnicity on MS risk are examined in the same
      series. Census data are used again to characterize the population ancestry of the
      state from which each subject entered active duty (EAD)--that is, the proportions
      of the populace reporting various ancestries--and subjects were also individually
      categorized into a single ethnic group, without knowledge of case/control status,
      based on surname. In this study population, categorized ethnicity was strongly
      correlated with population ancestry, as expected. Although univariate analyses
      showed statistically significant associations between MS risk and several surname
      derived ethnicities and ethnic groups, when residence at EAD was accounted for as
      well, there was almost no ethnic variation in MS risk. A logistic regression
      analysis further showed that variations in MS risk are associated most strongly
      with latitude and population ancestry group; in particular, subjects who entered
      military service from states with higher proportions of Swedish or French
      ancestry had higher risks of MS. After adjustment for characteristics of place,
      the only significant individual ethnicity factor found was Southern European
      ethnicity. In general, we conclude that an individual's ethnicity seems to be of
      less relative importance in determining MS risk than is the population ancestry
      of the state of EAD. These findings underscore the fact that MS is a disease of
      place, with 'place' including not only attributes of the locale (e.g., latitude),
      but also of its populace (e.g., ancestry).

PMID- 8570001
TI  - Prevalence of movement disorders in institutionalized elderly.
AB  - The proportion of the population over age 65 years is steadily increasing in
      Canada and the elderly who are unable to live independently are frequently
      institutionalized in chronic care facilities. We report our observations on
      movement disorders (MD) in an institutionalized elderly population of
      Saskatchewan. A representative sample of 67 subjects aged > or = 65 years had a
      detailed neurological evaluation on three separate occasions. MD were detected in
      13 (19%) cases. The majority, 11 (16%), were females. Seven (10%) had essential
      tremor, 4 (6%) Parkinson's disease and 2 (3%) had drug-induced parkinsonism.

PMID- 8570002
TI  - Effect of a ubiquinone-like molecule on oxidative energy metabolism in rat
      cortical synaptosomes at different ages.
AB  - Persistent stimulation of energy consumption, induced by depolarization with
      veratridine, mimics a condition of abnormally enhanced energy demand and causes
      an increase in the oxygen consumption rate (QO2) and in the interconversion of
      pyruvate dehydrogenase complex (PDHc) into its active form. Wistar rats at the
      age of 26 months do not show alterations of QO2 and the ability of veratridine to
      increase QO2 in comparison with 6 month-old animals whereas the active form of
      PDHc is slightly but significantly reduced. Idebenone, a ubiquinone-like molecule
      (1 microM), does not affect the QO2 or PDHc activation state in resting
      conditions but attenuates the veratridine-challenged increase in QO2 at all the
      ages tested and attenuates the increase in the percentage of PDHa reaching
      statistical significance in 26-month-old rats. At higher concentration (10
      microM) idebenone totally abolishes the veratridine-induced increase in PDHa also
      in the 6 month-old rats. At the lower concentration, the drug does not affect the
      increase in QO2 induced by an uncoupler of oxidative phosphorylation. The results
      obtained suggest a protective effect of idebenone on the cerebral tissue against
      stressful conditions; this action may be exerted at the level of some
      mitochondrial component and/or on the Na+ homeostasis.

PMID- 8570003
TI  - Flow threshold for enhanced phorbol ester binding in the ischemic gerbil brain.
AB  - The correlation between regional phorbol ester binding and cerebral blood flow
      (CBF) was evaluated in the gerbil brain after 2-hour unilateral common carotid
      artery occlusion. [3H]phorbol 12,13-dibutyrate (PDBu) was used as a specific
      ligand for estimating the translocation of protein kinase C (PKC), and CBF was
      determined by the [14C]iodoantipyrine method. A quantitative autoradiographic
      method permitted concurrent measurement of these two parameters in the same
      brain. In the ischemia group of the animals, statistically significant, inverse
      correlations were noted between the CBF and PDBu binding in the hippocampus (CA1
      and CA3 regions and dentate gyrus), the caudate-putamen and lateral nuclei of the
      thalamus. In these regions, the PDBu binding increased progressively as CBF fell
      below 35-40 ml/100 g/min. On the other hand, the PDBu binding in the cerebral
      cortices did not show any significant changes even when CBF was decreased to
      below 35 ml/100 g/min. The above data suggest that (1) the translocation of PKC
      to the cell membrane may be regionally specific in response to ischemia, and may
      remain in the regions particularly vulnerable to ischemia such as the
      hippocampus, caudate-putamen and lateral nuclei of the thalamus in the early
      ischemic phase; (2) the threshold of CBF below which PKC begins to translocate to
      the cell membrane in the above regions, may be 35-40 ml/100 g/min in 2-hour
      ischemia.

PMID- 8570004
TI  - Deoxyglucose uptake by mouse astrocytes: effects of temperature and retrovirus
      infection.
AB  - Deoxyglucose uptake by FVB/N mouse astrocytes was studied before and after
      infection by ts1 retrovirus which causes a neurodegenerative disease in mice
      similar to HIV-1 encephalopathy in man. The Michaelis-Menten kinetic parameters,
      Km and Vmax, of 2-deoxy-D-glucose uptake by brain and cerebellar astrocytes were
      measured following culture at 34 degrees C where ts1 retrovirus replicates
      optimally, and at 37 degrees C. Compared to astrocytes cultured at 37 degrees C,
      astrocytes cultured at 34 degrees C had increased Km and decreased deoxyglucose
      uptake despite increased or unchanged Vmax. Following ts1 retrovirus infection,
      brain astrocyte deoxyglucose uptake doubled [132%] associated with decreased Km
      but unchanged Vmax, whereas cerebellar astrocyte deoxyglucose uptake doubled
      [102%] associated with increased Vmax but unchanged Km. These observations of
      altered deoxyglucose uptake kinetic parameters following retrovirus infection
      indicate different neurochemical mechanisms for the regional variation in
      deoxyglucose uptake observed following retrovirus infection of the CNS in vivo.

PMID- 8570005
TI  - Acetyl-L-carnitine attenuates neuronal damage in gerbils with transient forebrain
      ischemia only when given before the insult.
AB  - The underlying mechanisms leading to neuronal damage in cerebral ischemia are
      multifactoral. In this study, we evaluated the neuroprotective effects of acetyl
      L-carnitine, a medication that may enhance metabolic recovery after cerebral
      ischemia. The 5-minute transient forebrain ischemia model in gerbils was used.
      Acetyl-L-carnitine was given 30 minutes before the insult in one set of animals
      and 30 minutes after the insult in a second set of animals with histological
      evaluation at 7 days (Group A) and 28 days (Group B). Damage assessment was done
      using a 4-point damage score and Mann-Whitney U test was used for statistical
      analysis. Compared to the controls, there was significant protection in the
      cerebral cortex, hippocampus and the striatum in animals treated with the
      medication before the insult in Group A and Group B. Post-ischemic therapy showed
      little evidence of neuronal protection in either group. Behavioral tests in the
      Group B animals showed no significant differences between the treated or the
      saline controls. Our study shows, that pre-ischemic treatment with acetyl-L
      carnitine results in neuronal protection. This may have clinical significance in
      situations (such as bypass surgery) where treatment could be initiated prior to
      the insult.

PMID- 8570006
TI  - Protein kinase C inhibitors affect induction of long-lasting potentiation in the
      somatosensory cortex.
AB  - The effects of protein kinase C (PKC) inhibitors on the induction of long lasting
      potentiation (LLP) of field potentials in the feline somatosensory cortex were
      studied. LLP was induced by high frequency stimulation (HFS, 200 Hz) of the
      ventral posterolateral thalamic nucleus. First, the effects of a protein kinase
      inhibitor, H-7, and a specific PKC catalytic domain inhibitor, chelerythrine, on
      the LLP in the secondary somatosensory cortex (SII) were investigated.
      Intracortical microinjections of H-7 and chelerythrine at 30 min before HFS
      inhibited induction of LLP in SII, while an injection of chelerythrine at 60 min
      after LLP induction had no effect on the potentiation. Second, changes in PKC
      activity in the presence of calcium and phosphatidylserine were investigated in
      SII after induction of LLP. Triton-soluble membrane fractional PKC activity had
      increased to 350% of the control value with low frequency test stimulation (0.1
      Hz) by five min after HFS. In contrast, PKC activities of cytosolic fractions
      decreased to 25.6% of the control value. At 60 min after HFS, the PKC activity
      level returned to the control value, despite persistent potentiation in all
      cases. PKC activation is considered to be one of the factors required for
      induction of LLP but not for maintenance in SII.

PMID- 8570007
TI  - Modulation of adenosine-induced cAMP accumulation via metabotropic glutamate
      receptors in chick optic tectum.
AB  - Changes on cyclic adenosine monophosphate (cAMP) levels in response to adenosine
      and glutamate and the subtype of glutamate receptors involved in this interaction
      were studied in slices of optic tectum from 3-day-old chicks. cAMP accumulation
      mediated by adenosine (100 microM) was abolished by 8-phenyltheophylline (15
      microM). Glutamate and the glutamatergic agonists kainate or trans-D, L-1
      aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) did not evoke cAMP
      accumulation. Glutamate blocked the adenosine response in a dose-dependent
      manner. At 100 microM, glutamate did not inhibit the effect of adenosine. The 1
      mM and 10 mM doses of glutamate inhibited adenosine-induced cAMP accumulation by
      55% and 100%, respectively. When glutamatergic antagonists were used, this
      inhibitory effect was not affected by 200 microM 6,7-dihydroxy
      2,3,dinitroquinoxaline (DNQX), an ionotropic antagonist, and was partially
      antagonized by 1 mM (RS)-alpha-methyl-4-carboxyphenylglycine [(RS)M-CPG], a
      metabotropic antagonist, while 1 mM L-2-amino-3-phosphonopropionate (L-AP3)
      alone, another metabotropic antagonist, presented the same inhibitory effect of
      glutamate. Kainate (10 mM) and trans-ACPD (100 microM and 1 mM) partially blocked
      the adenosine response. This study indicates the involvement of metabotropic
      glutamate receptors in adenylate cyclase inhibition induced by glutamate and its
      agonists trans-ACPD and kainate.

PMID- 8570008
TI  - Bradykinin stimulates phospholipase D in PC12 cells by a mechanism which is
      independent of increases in intracellular Ca2+.
AB  - These experiments were designed to learn the role of bradykinin induced changes
      in intracellular Ca2+ in the activation of phospholipase D activity in PC12
      cells. Ionomycin at a concentration of 0.1 microM caused an increase in
      intracellular Ca2+ comparable to bradykinin, but had no effect on phospholipase D
      activity. Carbachol, ATP, and thapsigargin also increased intracellular Ca2+ but
      had no effect on phospholipase D activity. Increases in intracellular Ca2+ may be
      a necessary but not a sufficient factor in the activation of phospholipase D. To
      investigate this issue, the bradykinin induced increase in intracellular Ca2+ was
      blocked by preincubating the cells in Ca(2+)-free media plus EGTA or in media
      containing the intracellular Ca2+ chelator BAPTA/AM. These preincubations
      completely blocked the bradykinin induced increase in intracellular Ca2+ but only
      attenuated the bradykinin mediated activation of phospholipase D. Physiological
      increases in intracellular Ca2+ apparently do not mediate the effect of
      bradykinin on phospholipase D.

PMID- 8570009
TI  - Regulation of fructose-1,6-bisphosphatase activity in primary cultured
      astrocytes.
AB  - In the gluconeogenic pathway, fructose-1,6-bisphosphatase (EC 3. 1. 3. 11) is the
      last key-enzyme before the synthesis of glucose-6-phosphate. The extreme
      diversity of cells present in the whole brain does not facilitate in vivo study
      of this enzyme and makes it difficult to understand the regulatory mechanisms of
      the related carbohydrate metabolism. It is for instance difficult to grasp the
      actual effect of ions like potassium, magnesium and manganese on the metabolic
      process just as it is difficult to grasp the effect of different pH values and
      the influence of glycogenic compounds such as methionine sulfoximine. The present
      investigation attempts to study the expression and regulation of fructose-1,6
      bisphosphatase in cultured astrocytes. Cerebral cortex of new-born rats was
      dissociated into single cells that were then plated. The cultured cells were flat
      and roughly polygonal and were positively immunostained by anti-glial fibrillary
      acidic protein antibodies. Cultured astrocytes are able to display the activity
      of fructose-1,6-bisphosphatase. This activity was much higher than that in brain
      tissue in vivo. Fructose-1,6-bisphosphatase in cultured astrocytes did not
      require magnesium ions for its activity. The initial velocity observed when the
      activity was measured in standard conditions was largely increased when the
      enzyme was incubated with Mn2+. This increase was however followed by a decrease
      in absorbance resulting in the induction, by the manganese ions, of a singular
      kinetics in the enzyme activity. Potassium ions also stimulated fructose-1,6
      bisphosphatase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570010
TI  - Inhibition by veratridine of carbachol-stimulated inositol tetrakisphosphate
      accumulation in rat brain cortical slices.
AB  - The present studies examined the inhibitory effect of veratridine (a Na+ channel
      activator) on carbachol (a cholinergic agonist) stimulated inositol 1,3,4,5
      tetrakisphosphate accumulation in rat brain cortical slices. Veratridine
      inhibited carbachol stimulation of inositol 1,3,4,5-tetrakisphosphate formation
      (after a delay of about 30 seconds) at 60 or 120 seconds when there was little
      inhibition of inositol 1,4,5 trisphosphate accumulation. The inhibitory effect of
      veratridine on carbachol stimulated inositol 1,3,4,5-tetrakisphosphate
      accumulation was abolished in the presence of ouabain or tetrodotoxin but was
      unaffected in low calcium conditions. Veratridine reduced the total ATP content
      and this effect was abolished by tetrodotoxin. The inhibitory effect of 10 but
      not 30 microM veratridine on inositol 1,3,4,5-tetrakisphosphate accumulation in
      the presence of carbachol was reversed by the presence of exogenous 8-bromo
      cyclic AMP or forskolin which activates adenylyl cyclase. However, the decrease
      in brain slice ATP seen in the presence of veratridine was unaffected by
      forskolin. Our results are compatible with the hypothesis that veratridine
      inhibition of carbachol-stimulated inositol 1,3,4,5-tetrakisphosphate formation
      is due to depletion of ATP at the site of Ins 1,3,4,5-P4 formation from Ins 1,4,5
      P3.

PMID- 8570011
TI  - omega-Aga IVA selectively inhibits the calcium-dependent fraction of the evoked
      release of [3H]GABA from synaptosomes.
AB  - The effect of omega-Aga IVA, a P-type Ca2+ channel blocker, on the release of the
      inhibitory neurotransmitter GABA and on the elevation of Cai induced by
      depolarization was investigated in [3H]GABA and fura-2 preloaded mouse brain
      synaptosomes, respectively. Two strategies (i.e. 20 mM external K+ and
      veratridine) that depolarize by different mechanisms the preparation were used.
      High K+ elevates Cai and induces [3H]GABA release in the absence of external Na+
      and in the presence of TTX, conditions that abolish veratridine induced
      responses. The effect of omega-Aga IVA on the Ca2+ and Na+ dependent fractions of
      the depolarization evoked release of [3H]GABA were separately investigated in
      synaptosomes depolarized with high K+ in the absence of external Na+ and with
      veratridine in the absence of external Ca2+, respectively. The Ca2+ dependent
      fraction of the evoked release of [3H]GABA and the elevation of Ca2+ induced by
      high K+ are markedly inhibited (about 50%) in synaptosomes exposed to omega-Aga
      IVA (300 nM) for 3 min before depolarization, whereas the Na+ dependent, Ca2+
      independent carrier mediated release of [3H]GABA induced by veratridine, which is
      sensitive to verapamil and amiloride, is not modified by omega-Aga IVA. Our
      results indicate that an omega-Aga IVA sensitive type of Ca2+ channel is highly
      involved in GABA exocytosis.

PMID- 8570012
TI  - Characterization of the type of calcium channel primarily regulating GABA
      exocytosis from brain nerve endings.
AB  - In an attempt to further characterize the type of Ca2+ channels primarily
      regulating GABA exocytosis, the effects of increasing concentrations of omega CTx
      MVIIC,-omega-Aga IVA and other Ca2+ channel blockers (nitrendipine, Cd2+ and
      Ni2+), commonly used for pharmacologically discerning among the various types of
      Ca2+ channels, were tested on the dissected Ca2+ dependent fraction of the
      depolarization evoked release of GABA from mouse brain synaptosomes. Our results
      show that omega-CTx MVIIC inhibits GABA exocytosis with a calculated IC50 of 3
      microM and omega-Aga IVA with a calculated IC50 of 50 nM. The divalent cation
      Cd2+ only diminishes GABA exocytosis at 70 microM, but does not modify this
      response at lower concentrations (i.e. 1 and 10 microM). Neither nitrendipine (10
      microM) nor Ni2+ (100 microM and 500 microM) modified GABA exocytosis. The
      failure of nitrendipine at a high concentration to inhibit GABA exocytosis
      discards L-type Ca2+ channels as the main regulators of this response; likewise
      that of Ni2+ discards Ca2+ channels of the N-type, and the failure of nM
      concentrations of omega-CTx MVIIC or 500 microM Ni2+, also discards alpha 1A/Q
      type Ca2+ channels as the main regulators of the GABA response. On the basis of
      these results and in particular of the higher potency of omega-Aga IVA than omega
      CTx MVIIC, it is concluded that the type of Ca2+ channels that primarily
      determine the exocytosis of GABA belong to a P-like type of Ca2+ channels.

PMID- 8570013
TI  - Metrifonate effects on acetylcholine and biogenic amines in rat cortex.
AB  - The effect of systemic and local administration of metrifonate (MTF), a long
      acting cholinesterase inhibitor (ChEl) on extracellular levels of acetylcholine
      (ACh), norepinephrine (NE), dopamine (DA) and serotonin (5-HT) was investigated
      in the rat cortex by using transcortical microdialysis. Metrifonate (20, 40, and
      80 mg/kg, s.c.) increased ACh levels in a dose-dependent manner above the
      baseline. Two consecutive administrations (80 mg/kg) enhanced ACh levels
      producing two similar patterns of elevation. A significant increase in NE was
      also seen at 80 mg/kg. Systemic administration (20 mg/kg) of MTF produced a
      significant increase of DA levels. Local cortical perfusion of MTF through the
      probe caused a significant but slow increase of ACh as well as an increase of NE
      levels. Compared to NE, the elevation of DA was more rapid and more long-lasting.
      The cortical levels of 5-HT were not modified by MTF given by either route. These
      results support the concept of MTF being a potential drug for treatment of
      Alzheimer disease (AD).

PMID- 8570014
TI  - 5-fluoronicotine, noranhydroecgonine, and pyridyl-methylpyrrolidine release
      acetylcholine and biogenic amines in rat cortex in vivo.
AB  - The effects of nicotinic receptor agonists 5-fluoronicotine, noranhydroecgonine
      and pyridyl-methylpyrrolidine on the cortical release of acetylcholine (ACh),
      norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were investigated with
      microdialysis in rat. 5-Fluoronicotine significantly elevated ACh to 76% above
      basal values and DA to 69% above baseline. Pyridyl-methylpyrrolidine
      significantly increased the release of ACh to 39% above basal values and NE to
      63% above baseline. Noranhydroecgonine significantly elevated NE to 64% above
      basal values and DA to 147% above baseline. 5-Fluoronicotine did not affect NE
      release; pyridylmethylpyrrolidine did not alter DA release; and
      noranhydroecgonine did not significantly elevate ACh release. None of these
      agonists increased the release of 5-HT. All responses were blocked by prior
      administration of mecamylamine, a nicotinic receptor antagonist. The distinctive
      neurotransmitter-related profiles for the three agonists are suggestive of
      activity at subtypes of nicotinic receptors, an effect that may be related to the
      structural diversity of these compounds.

PMID- 8570015
TI  - Neurofilament phosphorylation and [125I]calmodulin binding by Ca2+/calmodulin
      dependent protein kinase in the brain subcellular fractions of diisopropyl
      phosphorofluoridate (DFP)-treated hen.
AB  - Diisopropyl phosphorofluoridate (DFP) produces organophosphorus ester-induced
      delayed neurotoxicity (OPIDN) in humans and sensitive animal species, e.g., adult
      chicken. The chickens were sacrificed 18 days after a single dose of DFP (1.7
      mg/kg, s.c.), which produced severe ataxia or paralysis in 10-14 days. We studied
      Ca2+/calmodulin-dependent in vitro neurofilament phosphorylation by the brain
      subcellular fractions of control and DFP-treated hens. There was enhanced
      phosphorylation of all three NF subunits by the brain supernatant of treated
      hens. This was accompanied by enhanced autophosphorylation of both Ca2+/CaM
      dependent protein kinase II (CaM-kinase II) subunits and increased calmodulin
      binding using either 125I-CaM or biotinylated calmodulin to only alpha subunit
      without concomitant increase in the amount of this enzyme. This enhanced
      phosphorylation of neurofilament subunits was completely and partially inhibited
      by mastoparan and KN-62, respectively. There was no alteration in the
      distribution of CaM-kinase II activity in treated hens and the activity was not
      related to its concentration in different subcellular fractions. The difference
      in 125I-CaM binding to CaM-kinase II alpha subunit in the brain supernatants of
      control and DFP-treated hens was not altered by its phosphorylation or
      dephosphorylation. The increased CaM-kinase II activity in the soluble fraction
      of DFP-treated hen brain may be involved in the aberrant phosphorylation of
      axonal neurofilaments, and thus play a role in OPIDN.

PMID- 8570017
TI  - HPLC/RIA analysis of bioactive methionine enkephalin content in the seizure
      susceptible El mouse brain.
AB  - We previously reported a deficit of methionine enkephalin-like immunoreactivity
      (ME-LI), in the cerebral cortex, septal area, hippocampus, and striatum and the
      abnormal metabolism of opioid peptides in the hippocampus and striatum of seizure
      susceptible El mice, which are involved in the pathogenesis of seizures. However,
      these findings suggest that the ME-LI does not necessarily reflect the bioactive
      methionine enkephalin (ME). Herein, we measured the biologically active peptide,
      ME excluding cross-reactive substances by using HPLC coupled with
      radioimmunoassay to clarify the abnormal function of enkephalinergic neurons in
      the El mouse brain. The ME content in 25-day-old El mice that had no seizures was
      significantly decreased in the hippocampus and septal area, as compared with
      corresponding regions in ddY mice (seizure-nonsusceptible; the mother strain of
      El). At the age of 50 days when El mice displayed abortive seizures, this content
      in both stimulated El[s] and nonstimulated El[ns] was significantly reduced in
      the septal area and cerebral cortex. At the age of 150 days when El mice exhibit
      tonic-clonic seizures, this content in both El[s] and El[ns] was significantly
      reduced in the septal area, cerebral cortex and striatum. These findings were
      generally compatible with our previous findings. This study further supports our
      hypothesis that a deficit of anticonvulsant endogenous ME, in the cerebral
      cortex, septal area, and hippocampus of seizure-susceptible El mice play an
      important role in the pathogenesis of seizures.

PMID- 8570016
TI  - Specificity of zinc binding to myelin basic protein.
AB  - Zn2+ appears to stabilize the myelin sheath but the mechanism of this effect is
      unknown. In a previous report we have shown that zinc binds to CNS myelin basic
      protein (MBP) in the presence of phosphate and this results in MBP aggregation.
      For this paper we used a solid phase zinc blotting assay to identify which myelin
      proteins bind zinc. MBP and a 58 kDa band were found to be the major targets of
      65Zn binding. Moreover, using fluorescence, light scattering and electron
      microscopy we investigated the binding of zinc and other cations to purified MBP
      in solution. Among the cations tested for their ability to interfere with the
      binding of zinc, the most effective were cadmium, mercury and copper, but only
      cadmium and mercury increased the scattering intensity, whereas MBP aggregation
      was not inhibited by copper ions. Thus, the effect of zinc on the formation of
      MBP clusters seems to be specific.

PMID- 8570018
TI  - Activation of 5-HT1A receptors inhibits carbachol-stimulated inositol 1,4,5
      trisphosphate mass accumulation in the rodent hippocampus.
AB  - We have previously demonstrated that 5-HT1A receptor agonists partially prevent
      the stimulation by carbachol of [3H]-phosphoinositide hydrolysis in immature rat
      hippocampal slices. This negative modulation has been investigated further by
      measuring, using a radioreceptor assay, the mass accumulation of IP3. In
      hippocampal slices from developing rats and in hippocampal neurons, carbachol
      enhanced the accumulation of IP3 and this response was partially inhibited by 8
      OH-DPAT with a potency compatible with the affinity of this agonist for 5-HT1A
      receptors. The inhibition of the carbachol response by 8-OH-DPAT was non
      competitive in nature and 8-OH-DPAT did not affect the inhibitory potency of
      pirenzepine. The inhibitory effect of 8-OH-DPAT was maintained after washing the
      slices preincubated with this compound but was not observed on the carbachol
      stimulated PIP2 hydrolysis in hippocampal membranes, suggesting that this
      compound induces long lasting changes of muscarinic receptors and/or their
      effector mechanism by an indirect action.

PMID- 8570019
TI  - Astrocyte differentiation is enhanced in chick embryos treated with ethanol
      during early neuroembryogenesis.
AB  - In this study, we examined the effects of ethanol administered to chick embryos,
      on the maturation of astrocytes, using glutamine synthetase (GS) activity as an
      astrocyte marker. Ethanol (50 mM) was administered in ovo via the air sac,
      embryos were sacrificed at various days of embryonic development and GS activity
      was determined in cerebral hemispheres and cerebellum. We found that in both
      cerebral hemispheres and cerebellum, GS activity was higher in the ethanol
      treated embryos, as compared to controls, during the embryonic periods, E6 to E10
      in the cerebral hemispheres and E10 to E14 in the cerebellum. These periods are
      characterized by increased neuronal differentiation in these CNS areas. The
      increase in GS activity in the ethanol-treated embryos is speculated to reflect
      either a transient reactive gliosis and/or an enhancement in the differentiation
      of radial glia, immature glia, to more mature astrocytes.

PMID- 8570020
TI  - Enzymes and inhibitors in leu-enkephalin in metabolism in human plasma.
AB  - The enzymes degrading leucine enkephalin in human plasma and the inhibitors
      active on these enzymes were studied by kinetic and chromatographic techniques.
      Data obtained evidence the existence of complex kinetics of leu-enkephalin
      hydrolysis and of formation of its hydrolysis by-products. These appear to
      originate from the combined effect of further hydrolysis of the enkephalin's
      fragments after their release and of competition between the different enzymes
      present in plasma. Chromatographic separation of plasma proteolysis inhibitors
      indicates the existence of several pools of substances acting on all three enzyme
      groups that degrade leu-enkephalin. The partial specificity of these substances
      induces competition effects: consequently, the actual protection over leu
      enkephalin is considerably lower that the total inhibitory activity. That
      notwithstanding, plasma inhibitors control enkephalin hydrolysis to a relevant
      extent, while they modify only slightly the ratio of hydrolysis between the
      different enzymes. This latter parameter--and specifically the large prevalence
      of aminopeptidases over dipeptidylaminopeptidases and dipeptidylcarboxypeptidases
      -appears controlled mainly by kinetic factors.

PMID- 8570021
TI  - Structure and function of the NMDA receptor channel.

PMID- 8570023
TI  - Excitatory amino acid induced currents of isolated murine hypothalamic neurons
      and their suppression by 2,3-butanedione monoxime.
AB  - Ionic currents induced by excitatory amino acids were investigated for freshly
      isolated murine hypothalamic neurons with whole cell recording techniques. L
      glutamate or N-methyl-D-aspartate (NMDA), in combination with glycine, resulted
      in a rapidly rising current which decayed in the continued presence of agonist.
      In contrast, kainate currents did not decay. While quisqualate-induced current
      maintained a steady amplitude in the continued presence of agonist, a rapid decay
      phase appeared at holding potentials negative to -50 mV. Co-application of 2,3
      butanedione monoxime (BDM) reversibly inhibited the currents due to each agonist.
      Detailed study of BDM suppression of kainate-induced current revealed two
      components. A component with a rapid onset did not involve phosphatase action
      since 500 microM ATP-gamma-S or a protein kinase inhibitor (H-7, 200 microM) did
      not alter current suppression or recovery after BDM. Thus, the probable mechanism
      for this component of BDM's effect is direct block of the kainate-activated ion
      channel. However, preincubating neurons with 30 mM BDM reduced their subsequent
      response to kainate alone. This persistent effect of BDM was not seen for neurons
      dialyzed with a solution containing ATP-gamma-S during conventional whole cell
      recording. Furthermore, exposure to H-7 prevented recovery of the kainate
      response suppressed by preincubation in BDM. These findings suggest that BDM
      causes sustained suppression of the kainate response of hypothalamic neurons via
      a "chemical phosphatase" action.

PMID- 8570022
TI  - Comparison of the potency, kinetics and voltage-dependency of a series of
      uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor
      impairment activity in vivo.
AB  - The amino-adamantane derivatives memantine (1-amino-3,5-dimethyladamantane) and
      amantadine (1-amino-adamantane) are relatively low affinity, uncompetitive N
      methyl-D-aspartate (NMDA) receptor antagonists which have been used clinically in
      the treatment of dementia and Parkinson's disease respectively for several years
      without serious side effects. The aim of this study was to test whether
      memantine, amantadine and other low affinity uncompetitive NMDA receptor
      antagonists also have better therapeutic indices than high affinity antagonists
      in preclinical models of epilepsy by assessing the potency, kinetics and voltage
      dependency of open channel blockade for a series antagonists in vitro and
      comparing these effects to anticonvulsive and motor impairment activity in vivo.
      The compounds tested were memantine, amantadine, 14 other amino-adamantanes, (+)
      MK-801, ketamine, dextrorphan, dextromethorphan and phencyclidine. The offset
      kinetics of open-channel blockade assessed with whole cell patch clamp recordings
      from cultured superior colliculus neurones were highly correlated to potency i.e.
      the less potent antagonists showed faster unblocking kinetics (Koff, r = 0.904).
      Although, onset kinetics as assessed by Kon were not correlated to potency (r =
      0.023), tau on estimated at IC50 is perhaps a more meaningful measure of onset
      kinetics at equieffective concentrations and was also well correlated to potency
      (r = -0.863). All amino-adamantanes tested were strongly voltage-dependent. There
      was also a good correlation between the in vitro potencies of uncompetitive NMDA
      receptor antagonists assessed with patch clamp recordings and displacement of
      equilibrium [3H](+)-MK-801 binding and their in vivo activity against maximal
      electroshock (MES) and pentylenetetrazol (PTZ) induced tonic convulsions and NMDA
      induced lethality in mice. Memantine and four other amino-adamantanes with
      somewhat lower potency and faster blocking kinetics had better therapeutic
      indices (ED50 rotarod and traction reflex over ED50 in MES-induced convulsions;
      TI = 2-4) than substances with higher affinity such as ketamine, dextrorphan and
      (+)-MK-801 (TI < 2). However, amantadine and several other amino-adamantanes with
      lower potency than memantine actually had poorer therapeutic indices (TI < or =
      0.5) which may have been due to additional actions at other ion channels or
      receptors at the doses necessary to protect against seizures. In fact, ED50 in
      the MES test was negatively-correlated to therapeutic indices (traction r = 
      0.790, rotarod r = -0.797) i.e. the less potent uncompetitive antagonists had
      worse therapeutic indices. The data from the present study do not lend support to
      the idea that low affinity, open channel NMDA receptor blockers are also
      effective in models of epilepsy at doses having little effect on physiological
      processes. It should be stressed that these data do not contradict the known
      therapeutic safety of memantine and amantadine in dementia and Parkinson's
      disease respectively. Thus the good clinical profile of memantine in dementia has
      been attributed not only to its fast blocking/unblocking kinetics but also to its
      strong voltage-dependency. These biophysical properties may allow therapeutically
      relevant concentrations to block chronic, low level pathological activation of
      NMDA receptors whilst leaving their synaptic activation intact. Precisely these
      properties may also underlie the poor therapeutic indices seen in the present
      study on antiepileptic activity due to the synaptic nature of both seizures and
      normal glutamatergic transmission.

PMID- 8570024
TI  - Effect of lamotrigine on the electrically-evoked release of endogenous amino
      acids from slices of dorsal horn of the rat spinal cord.
AB  - The novel anti-epileptic, lamotrigine (LTG) has been shown to exhibit
      antinociceptive effects in the rat. In the present study, the effect of LTG on
      the electrically-evoked release of endogenous amino acids from rat isolated
      spinal dorsal horn slices with intact dorsal roots has been examined and compared
      with those of morphine in the same preparation. LTG (0.1-300 microM) inhibited
      the release of aspartate, glutamate and GABA in a concentration-dependent manner.
      The lowest concentrations of morphine (0.001-0.01 microM) enhanced the stimulated
      release of aspartate and glutamate while the higher concentrations inhibited
      their release. Stimulated GABA release was reduced in a concentration-dependent
      manner. The anticonvulsant was more potent at inhibiting the release of glutamate
      (IC50 = 20 microM) than that of GABA (IC50 = 44 microM) supporting the previous
      suggestion that lamotrigine is a selective inhibitor of glutamate release. This
      suggests that the reduction in glutamate release could be one of the mechanisms
      by which lamotrigine exerts its antinociceptive effect.

PMID- 8570025
TI  - The influence of experimental ischaemia on protein kinase C and the GABAergic
      system in the rabbit retina.
AB  - Pressure-induced ocular ischaemia followed by 25-28 hr of reperfusion to the
      rabbit retina drastically reduces or eliminates the b-wave of the
      electroretinogram and results in all the GABA from the amacrine cells being
      released, as judged by immunohistochemistry. Some of these GABA cells have the
      capacity to take-up exogenous serotonin and these GABA/serotonin cells have
      kainate/AMPA receptors. Previous studies have shown that an ischaemic insult
      causes these receptors to be stimulated to produce a release of the cells' GABA.
      The majority of the GABA/serotonin cells are also incapable of taking-up
      exogenous serotonin after ischaemia, which suggests that they are irreversibly
      damaged. However, there was still a minority of the cells which accumulated
      serotonin, which shows that neurones containing kainate/AMPA receptors are not
      irreversibly damaged at the same rate by ischaemia. The "staining" patterns for
      GABAA-receptor and GABA immunoreactivities in the rabbit retina are very similar
      and following ischaemia the GABAA-receptor immunoreactivity was reduced in
      intensity and became patchy in nature. It is not known whether this result
      reflects a down-regulation of the GABAA-receptors caused by the released GABA or
      a destruction of cells containing the GABAA-receptors. The ischaemic conditions
      used caused patchy, irregular and inconsistent signs of histological damage to
      the retina, even in areas of similar eccentricity, suggesting this parameter
      should be used with caution when judging the severity of an ischaemic insult.
      alpha-Protein kinase C (alpha PKC) present in the on-bipolar cells which have
      glutamate metabotropic APB receptors is both reduced or down-regulated and
      translocated by ischaemia. This is also the case for delta PKC which is absent
      from the on-bipolar cells. These data were established by a combination of
      immunohistochemistry and electrophoresis/blotting experiments. Enzyme analysis
      also showed that all PKC calcium-dependent and -independent isoenzymes, are
      translocated and reduced by ischaemia making it difficult to judge whether PKC
      inhibitors may be appropriate anti-ischaemic agents.

PMID- 8570026
TI  - Nicotinic and muscarinic receptor-evoked depolarizations recorded from a novel
      cortical brain slice preparation.
AB  - We have developed a novel cortical brain slice preparation for extracellular
      field-potential recording using the grease-gap barrier technique. This
      preparation allows the study of cholinergic and glutamatergic depolarization
      responses of neocortical pyramidal neurones whose axons pass through the corpus
      callosum to contralateral cortical areas. Concentration-effect curves to
      carbachol, 1,1-dimethyl-4-phenyl piperazinium (DMPP) and muscarine yielded mean
      EC50 values of 29.5, 13.2 and 17.7 microM, respectively. Carbachol-induced
      responses were antagonized by both atropine and mecamylamine in a manner
      consistent with agonist effects of carbachol at both nicotinic and muscarinic
      sites, while concentration-effect curves to DMPP and muscarine were shifted
      rightward in a parallel manner by mecamylamine (10 microM) and atropine (5 nM),
      with antagonist pKB estimates of 6.4 and 9.0, respectively. Depolarization
      responses to glutamate were reversibly antagonized by D-2-amino-5
      phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione; these
      antagonists had no effect on carbachol or DMPP-induced responses. This
      preparation allows reproducible quantification of depolarization responses of
      pyramidal neurones forming the corticocortical pathway, and indicates the
      presence of functional nicotinic and muscarinic receptors. We conclude that the
      preparation is a convenient model with which to test the efficacy of
      cholinomimetic agents in an intact neocortical system, and may be useful in the
      development of novel drugs for the treatment of the cognitive symptoms of
      Alzheimer's disease.

PMID- 8570027
TI  - The interactions of typical and atypical antipsychotics with the (-)2, 5,
      dimethoxy-4-methamphetamine (DOM) discriminative stimulus.
AB  - The present study was designed to test the hypothesis that atypical, but not
      typical, antipsychotics produce a functional in vivo blockade of 5-HT2A
      receptors. The magnitude of functional in vivo 5-HT2A receptor blockade elicited
      by representative compounds from each of the six major structural classes of
      typical antipsychotics, and the representative atypical antipsychotics clozapine
      and risperidone, was indicated by their respective abilities to block the
      stimulus effects of the phenylalkylamine hallucinogen (-)DOM in the rat.
      Chlorpromazine, thioridazine, fluphenazine, thiothixene and haloperidol did not
      produce a significant antagonism of the (-)DOM stimulus. The benzoxapine,
      loxapine (60%), and the atypical dibenzodiazepine, clozapine (62%), partially
      blocked and risperidone fully blocked (100%) the (-)DOM stimulus. None of these
      agents elicited significant levels of (-)DOM-appropriate responding when
      administered alone. These results indicate that the typical antipsychotics, with
      the exception of lozapine, fail to produce effective in vivo antagonism of 5-HT2A
      receptors at doses compatible with the preservation of operant behavior. In
      contrast, the atypical antipsychotics clozapine and risperidone elicit effective
      in vivo antagonism of 5-HT2A receptors without severe behavioral disruption.
      Thus, these data are supportive of the hypothesis that the mechanism of action of
      atypical, but not typical, antipsychotics involves the antagonism of 5-HT2A
      receptors in vivo.

PMID- 8570028
TI  - The effect of 5-HT1A receptor ligands in a chronic mild stress model of
      depression.
AB  - Antidepressant properties of 5-HT1A receptor ligands (the full agonist 8-OH-DPAT,
      the partial agonists ipsapirone and buspirone, and the selective antagonist WAY
      100135) were studied in a chronic mild stress model of depression. In this model,
      rats subjected to a variety of mild stressors for a prolonged period of time show
      a substantial decrease in the consumption of a 1% sucrose solution (anhedonia),
      an effect being sensitive to repeated treatment with antidepressant drugs. In the
      present study we found that the stress-induced deficit in the sucrose intake was
      gradually reversed by chronic (3-5 weeks) administration of buspirone (2.5 and 5
      mg/kg, i.p., b.i.d.) or WAY 100135 (10 mg/kg, s.c., b.i.d.), but not 8-OH-DPAT
      (0.5 mg/kg, s.c., b.i.d.) or ipsapirone (5 mg/kg i.p., b.i.d.). The magnitude of
      the effect of buspirone and WAY 100135 was comparable to that observed following
      similar administration of the antidepressant drugs imipramine (10 mg/kg i.p.) or
      citalopram (10 mg/kg i.p.). Increases in the sucrose intake following chronic
      treatment with buspirone, WAY 100135, imipramine and citalopram were specific to
      the stressed animals; the behaviour of control non-stressed animals was unchanged
      by any drug. These results suggest that buspirone and WAY 100135 may have
      antidepressant properties. Possible links between the anti-anhedonic effect of
      these drugs and their interaction with 5-HT1A receptors and/or the dopamine
      system are discussed.

PMID- 8570030
TI  - Serotonin turnover rate, [3H]paroxetine binding sites, and 5-HT1A receptors in
      the hippocampus of rats subchronically treated with clonazepam.
AB  - Selective central benzodiazepine agonists, such as clonazepam, are known to
      modify serotonin and 5-hydroxyindoleacetic content in the brain. In order to
      further study the effect of this benzodiazepine on serotonin turnover rate, rats
      received clonazepam, 10 mg/kg for 10 days, and the concentrations of serotonin
      and 5-hydroxyindoleacetic acid were determined in the hippocampus after
      inhibition of monoamineoxidase with pargyline. The results indicate a reduction
      in the turnover rate of the monoamine. In addition, the systemic administration
      of clonazepam produced a decrease in the Bmax of [3H]DPAT binding to 5-HT1A sites
      in the hippocampus. By contrast, this effect was not observed if clonazepam was
      delivered into the dorsal raphe nucleus by osmotic minipumps. The binding of
      [3H]paroxetine to 5-HT reuptake sites was increased by the treatment with
      clonazepam. The present observations indicate that clonazepam produces a
      reduction of serotonin turnover rate in the hippocampus of the rat concomitant
      with a down-regulation of 5-HT1A binding sites, probably by an effect at the
      forebrain projections. There is also an up-regulation of the serotonin
      transporter, which might contribute to a reduction in the synaptic availability
      of serotonin during clonazepam treatment.

PMID- 8570029
TI  - Characterization of 5-hydroxytryptamine1A properties of flesinoxan: in vivo
      electrophysiology and hypothermia study.
AB  - Flesinoxan is a high affinity and selective 5-hydroxytryptamine1A (5-HT1A) ligand
      which, unlike the 5-HT1A agonists of the azapirone class, does not generate 1-(2
      pyrimidinyl)piperazine, an alpha 2-adrenoreceptor antagonist. In view of
      potential antidepressant effects of flesinoxan, this study was undertaken to
      characterize its 5-HT1A properties in the rat brain using in vivo
      electrophysiology and hypothermia paradigms. The suppressant effect of
      microiontophoretic applications of flesinoxan on the firing activity of CA3
      pyramidal neurons was blocked by concomitant application of the 5-HT1A antagonist
      BMY 7378. Compared to gepirone, the efficacy of flesinoxan to suppress the firing
      activity of CA3 pyramidal neurons was significantly greater. While the
      coapplication of flesinoxan antagonized the suppressant effect of 5-HT on CA3
      pyramidal neurons, it failed to do so on dorsal raphe 5-HT neurons, indicating
      that flesinoxan acts as a partial agonist at postsynaptic and as a full agonist
      at presynaptic 5-HT1A receptors. The capacity of flesinoxan to antagonize the
      effect of 5-HT on CA3 pyramidal neurons was similar to that of 8-hydroxy-2-(di-n
      propylamino)-tetralin (8-OH-DPAT) and significantly greater than that of
      gepirone. The intravenous administration of flesinoxan suppressed the firing
      activity of both CA3 pyramidal neurons and dorsal raphe 5-HT neurons. However,
      when compared to 8-OH-DPAT, significantly higher doses of flesinoxan were
      required. The acute brain penetration of [3H]flesinoxan and [3H]8-OH-DPAT was,
      therefore, determined. Nine minutes after intravenous administration, [3H]8-OH
      DPAT reached significantly greater brain concentration than [3H]flesinoxan.
      Subcutaneous administration of flesinoxan and 8-OH-DPAT produced a dose-dependent
      hypothermia. The flesinoxan-induced hypothermia was significantly attenuated by
      prior administration of the non-selective 5-HT1A antagonist pindolol and the 5
      HT1/2 antagonist methysergide. Similar degrees of hypothermia were achieved with
      3 mg/kg of flesinoxan and 0.5 mg/kg of 8-OH-DPAT. The maximal effect of
      flesinoxan occurred 30 min later than that of 8-OH-DPAT and faded more slowly.
      The 5-HT1A properties of flesinoxan suggest that it may be an effective
      anxiolytic/antidepressant agent.

PMID- 8570031
TI  - Changes in G protein levels in the hippocampus and the striatum of rat brain
      after chronic treatment with haloperidol and sulpiride.
AB  - Treatment with either haloperidol or sulpiride for 14 days increased the levels
      of Gs alpha and Gi alpha in the rat hippocampus, but decreased those of Golf
      alpha and Gi alpha in the rat striatum. Levels of Gq alpha/G11 alpha and Go alpha
      were not affected by the drugs. These results demonstrate that haloperidol and
      sulpiride regulate G protein expression in the hippocampus and striatum quite
      differently.

PMID- 8570032
TI  - Metabotropic glutamate receptors are involved in TEA-induced long-term
      potentiation in area CA1 of the hippocampus.
AB  - A brief application of the K+ channel blocker tetraethylammonium induces a long
      lasting potentiation in the CA1 region of hippocampal slices (TEA LTP). We report
      here that metabotropic glutamate receptors (mGluRs) contribute to this kind of
      synaptic enhancement, since the mGluR antagonist (+)-alpha-methyl-4
      carboxyphenylglycine ((+) MCPG) inhibits TEA LTP with a concentration-dependent
      component.

PMID- 8570033
TI  - Structural organization of the synaptic connections of the spinal cord motor
      neurons of mammals.

PMID- 8570034
TI  - Influence of damage to the suprachiasmatic nuclei of the hypothalamus of rats on
      the dynamics of short-period fluctuations of normal and abnormal behavior.
AB  - An intensification of a swimming behavior with an increase in the proportion of
      active swimming and limitation of the duration of immobilization was found in
      rats following bilateral electrolytic destruction of the suprachiasmatic nuclei
      of the hypothalamus. The restructuring of the temporal dynamics of swimming is
      manifested in a limitation of the rhythmological index of depressivity. The
      animals with ablated nuclei demonstrate more pronounced behavioral disturbances
      in response to the introduction of fenamin and a slowing of the minute
      fluctuations in the dynamics of stereotypic behavior.

PMID- 8570035
TI  - Influence of perfusates of tetanized donor slices on the induction of long-term
      potentiation in recipient slices.
AB  - A perfusate collected from donor slices of the olfactory cortex of the brain of
      rats during tetanization of the lateral olfactory tract (100 imp/sec, 30 sec)
      induced prolonged changes in the amplitudes of various components of the focal
      potentials (FP) in recipient slices. When the perfusates are divided in relation
      to the reactions arising in the donor slices into three types, "potentiated,"
      "depressive," and "nonpotentiated," the reactions of the recipient slices prove
      to be diverse. The potentiated perfusate induced the development of depression.
      The depressive induced potentiation. The reactions of the recipient slices to the
      nonpotentiated perfusate were indeterminate. The data obtained suggest the
      secretion of active substances during the electrical tetanization of donor
      slices. These factors are capable of inducing reactions in the recipient slices
      which the donor slices had "experienced."

PMID- 8570036
TI  - Horizontal optokinetic nystagmus in the pigeon during static tilts in the frontal
      plane.
AB  - The influence of lateral static tilts of the body (30 degrees, 45 degrees) on
      horizontal optokinetic nystagmus induced by rotation of an optokinetic cylinder
      at a constant rate (16 degrees, 30 degrees/sec) was investigated in 16 pigeons.
      The experiments made it possible to identify a statistically significant tilt
      dependent asymmetry of the tonic otolithic influences on the optokinetic system
      which consisted in a marked inhibitory effect on horizontal optokinetic nystagmus
      of right-sided tilts by contrast with left-sided. The separate recording of
      oculomotor responses of the right and left eyes showed that the temporonasal
      nasotemporal (TN-NT) asymmetry of horizontal optokinetic nystagmus which exists
      in the norm in the pigeon is maintained under the conditions of stationary
      lateral tilts of the body for the eye which is in the upper position, and is
      replaced by a symmetrical pattern for the eye which is in the lower position. The
      results make it possible to hold the view that the mechanism of TN-NT asymmetry
      is controlled by otolithic inputs, and that its function may be substantially
      modified under the influence of the reorientation of the otolithic membranes in
      the gravitational field.

PMID- 8570037
TI  - Influence of emotional-algic stress on the activity of carboxypeptidase H--an
      enzyme involved in processing rat brain neuropeptides.
AB  - It was established that the activity of carboxypeptidase H increases in divisions
      of the brain of rats during a one-time emotional-algic stress. The most
      substantial increase in the activity of the enzyme is observed in the hypophysis
      and the hypothalamus. The changes in activity were less marked with chronic
      emotional-algic stress. The involvement of carboxypeptidase H in the development
      of stress reactions, as well as the possibility of the participation of the
      soluble form of the enzyme in the processing of secretory peptides, and of the
      membrane-bound form in the processing of neuropeptides with a central action, is
      hypothesized.

PMID- 8570038
TI  - Influence of the thyroid status of the organism in the realization of the
      adaptational effect of cold.
AB  - The combined three- and six-hour effect of immobilization and cold on euthyroid
      rats induces suppression of the contractile function and functional reserve of
      the heart, the death, respectively, of 30 and 80% of the animals, hypothermia,
      changes in the weight of the adrenals and the spleen, and ulceration of the
      mucosa of the stomach. Stressing of the hypothyroid rats is accompanied by a
      substantially more pronounced decrease in the indices of cardiac dynamics and the
      resistance of the organism after 3 h, and the death of 100% of the animals after
      6 h. The periodic effect of cold on euthyroid rats leads to an increase in the
      strength and speed of contraction and relaxation of the myocardium, as well as to
      an increase in the relative weight of the spleen. During subsequent stressing,
      cold adaptation substantially limits the disturbances in contractile function and
      prevents the decrease in the functional reserve of the heart, increases survival,
      and decreases the degree of hypothermia, ulcer-formation, and change in the
      weight of stress-sensitive organs, while the preventive effect of cold adaptation
      is absent in the hypothyroid animals; this attests to the significance of thyroid
      status for its realization.

PMID- 8570039
TI  - Spatial, bioelectrical, and neurochemical characteristics of the early afferent
      reaction of the caudate nucleus to an acoustic signal.

PMID- 8570040
TI  - Plastic reorganizations of the receptive fields of neurons of the auditory cortex
      and the medial geniculate body induced by microstimulation of the auditory
      cortex.
AB  - The receptive fields of neurons (RFs) whose activity was simultaneously recorded
      at several loci of the auditory cortex (AC) and in the medial geniculate body
      (MGB) were investigated before and after intracortical microstimulation (ICMS).
      Three types of neurons of the AC and MGB were distinguished on the basis of the
      character of the RFs: mono-, bi-, and polymodal. The RFs of the neighboring
      neurons in the AC (or in the MGB) could differ, while the RFs of remote neurons
      of the AC could be similar. The microstimulation of the AC could lead to changes
      in the RFs of neurons in the stimulated locus and neighboring loci of the AC, as
      well as in the loci of the MGB tonotopically associated with them. It is
      hypothesized that long-term modification of the efficiency of synaptic
      transmission between different elements of the cortex-thalamus-cortex circuit
      which arises as the result of the circulation of impulses along this chain during
      ICMS may be the mechanism underlying the observed changes in the RFs of AC and
      MGB neurons.

PMID- 8570041
TI  - Influence of small doses of dehydroepiandrosterone on the inception of the
      hormonal function of testes of sexually immature monkeys.

PMID- 8570042
TI  - Unusual subclavian steal: bidirectional and antegrade blood flow in the vertebral
      artery.
AB  - We present an unusual radiographic manifestation of subclavian steal seen in six
      patients. These cases differ from the classic form of subclavian steal in that
      antegrade and bidirectional blood flow in the vertebral-subclavian artery system
      is seen, resulting in the steal phenomenon.

PMID- 8570043
TI  - Iodixanol in intra-arterial cerebral digital subtraction angiography: a
      comparison with iohexol.
AB  - We randomised 86 patients undergoing intra-arterial cerebral digital subtraction
      angiography (IADSA) to receive iodixanol (Visipaque; Nycomed, Oslo, Norway) 150
      mgI/ml or iohexol (Omnipaque; Nycomed) 140 mgI/ml. The efficacy and safety of
      these two contrast media were compared: efficacy by evaluating the diagnostic
      information and radiographic density yielded by the angiograms, safety by
      recording all discomfort connected with the injections, and all adverse events up
      to 24 h after the investigation. Diagnostic information was optimal in all
      patients and the overall radiographic density optimal in all but one (iohexol) (P
      = 0.49). A feeling of warmth, the only discomfort reported, was experienced by
      43% and 54% of patients receiving iodixanol and iohexol, respectively (P = 0.26).
      Two patients in the iodixanol group and five in the iohexol group reported one
      adverse event (nausea, dizziness, visual disturbance or paraesthesiae) (P =
      0.30); all were of mild severity except for one moderate adverse event in each
      group. Iodixanol 150 mgI/ml and iohexol 140 mgI/ml were demonstrated to be
      suitable for IADSA, with no clinically or statistically significant differences
      in efficacy, discomfort or adverse events.

PMID- 8570044
TI  - Tissue characterisation of intracranial tumours: the value of magnetisation
      transfer and conventional MRI.
AB  - We performed MRI on 85 patients with intracranial tumours to evaluate
      quantitative analysis in tumour characterisation. Signal intensities were
      measured on standard T2- and T1-weighted images, Gd-enhanced T1-weighted images
      and magnetisation transfer (MT) images. Statistically significant differences
      between tumour types were observed, but overlapping reduces their value. T2
      weighted imaging was superior to T1-weighted imaging for tumour characterisation.
      Quantification of Gd enhancement was useful in the diagnosis of pituitary
      adenomas and haemangioblastomas, but of minor importance in other tumours,
      because of large nonspecific variation. The contribution of MT contrast to tumour
      characterisation resembled that of T2 contrast. However, MT imaging was superior
      to other sequences in the classification of intra-axial tumours. Low-grade
      astrocytomas, haemangioblastomas and craniopharyngiomas could be differentiated
      from other tumours on the basis of MT contrast. Reliable discrimination between
      meningiomas, high-grade astrocytomas and metastases was not possible by any of
      the methods.

PMID- 8570045
TI  - Differential diagnosis of extra-axial intracranial tumours by dynamic spin-echo
      MRI.
AB  - Dynamic MRI was performed on 22 patients with extra-axial intracranial tumours.
      Serial images were obtained every 30 s for 3 min using a spin-echo sequence (TR
      200, TE 15 ms) after rapid injection of Gd-DTPA, 0.1 mmol/kg body weight. The
      contrast medium enhancement ratio (CER) was correlated with the histology of the
      tumours. Meningiomas and extra-axial metastases showed a sharp rise, then a
      gradual decline. Although both had a definite early peak of CER, metastases
      showed a more rapid decline. Neuromas and extra-axial lymphoma showed a slow,
      steady increase with no peak within 180 s. This study indicates that the CER is
      helpful in the differentiation of extra-axial tumours.

PMID- 8570047
TI  - Serial MRI in early Creutzfeldt-Jacob disease with a point mutation of prion
      protein at codon 180.
AB  - We report a 66-year-old woman with histologically diagnosed Creutzfeldt-Jacob
      disease (CJD), followed with MRI from an early clinical stage. MRI demonstrated
      expansion of the high cortical signal on T2-weighted images, which differs from
      previous MRI reports of CJD. This patient followed an atypical clinical course:
      16 months had passed before she developed akinetic mutism, and periodic sharp
      waves had not been detected on EEG after 2 years in spite of her akinetic mutism.
      Brain biopsy showed primary spongiform changes in the grey matter, and a point
      mutation of the prion protein gene at codon 180 was discovered using polymerase
      chain reaction direct sequencing and Tth 111 I cutting. This is the first case
      with the point mutation of the codon 180 variant with an atypical clinical course
      and characteristic MRI findings.

PMID- 8570046
TI  - Functional mapping of the sensorimotor cortex: combined use of
      magnetoencephalography, functional MRI, and motor evoked potentials.
AB  - Combined use of magnetoencephalography (MEG), functional magnetic resonance
      imaging (f-MRI), and motor evoked potentials (MEPs) was carried out on one
      patient in an attempt to localise precisely a structural lesion to the central
      sulcus. A small cyst in the right frontoparietal region was thought to be the
      cause of generalised seizures in an otherwise asymptomatic woman. First the
      primary sensory cortex was identified with magnetic source imaging (MSI) of
      somatosensory evoked magnetic fields using MEG and MRI. Second, the motor area of
      the hand was identified using f-MRI during hand-squeezing. Then transcranial
      magnetic stimulation localised the hand motor area on the scalp, which was mapped
      onto the MRI. There was a good agreement between MSI, f-MRI and MEP as to the
      location of the sensorimotor cortex and its relationship to the lesion.
      Multimodality mapping techniques may thus prove useful in the precise
      localisation of cortical lesions, and in the preoperative determination of the
      best treatment for peri-rolandic lesions.

PMID- 8570048
TI  - Classification of brain compartments and head injury lesions by neural networks
      applied to MRI.
AB  - An automatic, neural network-based approach was applied to segment normal brain
      compartments and lesions on MR images. Two supervised networks, backpropagation
      (BPN) and counterpropagation, and two unsupervised networks, Kohonen learning
      vector quantizer and analog adaptive resonance theory, were trained on registered
      T2-weighted and proton density images. The classes of interest were background,
      gray matter, white matter, cerebrospinal fluid, macrocystic encephalomalacia,
      gliosis, and "unknown." A comprehensive feature vector was chosen to discriminate
      these classes. The BPN combined with feature conditioning, multiple discriminant
      analysis followed by Hotelling transform, produced the most accurate and
      consistent classification results. Classification of normal brain compartments
      were generally in agreement with expert interpretation of the images. Macrocystic
      encephalomalacia and gliosis were recognized and, except around the periphery,
      classified in agreement with the clinician's report used to train the neural
      network.

PMID- 8570049
TI  - CT of a peripatetic intracranial foreign body.
AB  - We report the CT appearances of a low-velocity missile that lodged within the
      brain and which subsequently migrated spontaneously back along the entry path. We
      review the literature of similar instances of migration and draw conclusions
      about the presurgical radiological management.

PMID- 8570050
TI  - Vascular contrast enhancement in Lhermitte-Duclos disease: case report.
AB  - We report a patient with surgically proven Lhermitte-Duclos disease. The
      radiologic and pathologic features of this cerebellar lesion are reviewed,
      including the newly reported presence of vascular contrast enhancement within the
      mass.

PMID- 8570051
TI  - A case of membranous lipodystrophy (Nasu-Hakola disease) with unique MRI
      findings.

PMID- 8570052
TI  - Calcified convexity dura mater and acute epidural haematoma mimicking calcified
      chronic subdural haematoma.
AB  - We report a patient with calcification of the convexity dura mater and an acute
      epidural haematoma. CT revealed a calcified layer between the haematoma and brain
      parenchyma, which mimicked acute bleeding into a calcified chronic subdural
      haematoma. The appearance of a calcified haematoma does not always mean a
      "chronic" lesion, and that emergency operation should not be foregone, when there
      is a history of acute head trauma and progressive impairment of consciousness.

PMID- 8570053
TI  - Frequency and severity of headache after lumbar myelography using a 25-gauge
      pencil-point (Whitacre) spinal needle.
AB  - We studied 63 patients between the ages of 20 and 81 years undergoing lumbar
      myelography, using a 25-gauge pencil-point (Whitacre) spinal needle. With the use
      of a questionnaire, the incidence and severity of post-dural-puncture headache
      (PDPH) was investigated. There were three patients who complained of PDPH (4.7%),
      two of whom described their headache as moderate and one as mild on a visual
      analogue scale. All the headaches were alleviated by mild analgesics and no
      patient experienced severe headache needing treatment with a blood-patch. There
      were three other patients who experienced a post dural-puncture-related headache
      which, unlike PDPH, was not postural. Four patients had ordinary mild headache.
      The quality of the myelograms was good.

PMID- 8570054
TI  - Resolution of pachymeningeal enhancement following dural puncture and blood
      patch.
AB  - We describe thickening and contrast enhancement of the intracranial
      pachymeninges, revealed by MRI in a patient with presumed low-pressure headache
      following dural puncture and a blood patch. The clinical and radiological
      abnormalities resolved within 2 weeks.

PMID- 8570055
TI  - Symptomatic cervical spondylolysis.

PMID- 8570056
TI  - Autoperfusion balloon catheter for treatment of vertebral artery stenosis.
AB  - Percutaneous transluminal angioplasty (PTA) of the vertebral artery was performed
      with an autoperfusion balloon catheter in five patients. There were no
      complications in the form of embolic episodes or neurological deficits due to
      brain ischaemia during inflation. In critical cases with insufficient collateral
      circulation during temporary occlusion, the use of an autoperfusion balloon
      catheter may expand the indications for PTA in patients with ischaemic
      cerebrovascular disease.

PMID- 8570057
TI  - Cholesterol granuloma in the middle cranial fossa: report of two cases.
AB  - We report two cases of cholesterol granuloma in the middle cranial fossa. On CT
      the lesions appeared as a nonspecific, nonenhancing soft-tissue mass with bone
      erosion. On MRI they were seen as areas of high signal intensity surrounded by a
      low-intensity peripheral zone on both T1- and T2-weighted images. Cholesterol
      granuloma is thought to occur when pneumatised cells in the temporal bone become
      obstructed. Although this lesion usually occurs in the petrous bone, it can
      extend to the middle cranial fossa. The diagnosis and surgical management are
      discussed.

PMID- 8570058
TI  - Localised proton magnetic resonance spectroscopy in X-linked
      adrenoleukodystrophy.
AB  - We have performed localised proton magnetic resonance spectroscopy (MRS) of the
      brain on four patients with X-linked adrenoleukodystrophy (X-ALD). The spectrum
      is characterised at the beginning of the disease by a decrease in N
      acetylaspartate and phosphocreatine-creatine content. Choline is strongly
      increased, and lactate can be detected in some cases. A proton signal from the
      CH2 groups borne by free intracellular very long chain fatty acids can also be
      observed. Later in the disease, the levels of all metabolites, in particular NAA,
      decrease significantly. The progression of neurometabolism documented by MRS
      correlates well with MRI and clinical progression on follow-up study. In one
      case, the metabolic profile recorded by proton MRS was abnormal before any change
      occurred on MRI. Proton MRS of the brain might be the method of choice for
      monitoring patients with X-ALD, to screen presumed cases and to study the effects
      of treatment.

PMID- 8570059
TI  - MRI of white matter changes in the Sjogren-Larsson syndrome.
AB  - We report a case of Sjogren-Larsson syndrome with spastic diplegia and conduction
      aphasia. MRI demonstrated the white matter changes deep in the cerebral
      hemispheres. We analyse the MRI findings and compare the results with
      neuropsychological signs.

PMID- 8570060
TI  - Childhood neuroborreliosis: clinicoradiological correlation.
AB  - We report the cranial CT and MRI findings in three children with Lyme disease
      (neuroborreliosis). The neuroimaging findings in children have been rarely
      reported. We found cranial MRI far superior to cranial CT. Ring-enhancing lesions
      have been described in acute disseminating encephalomyelitis and multiple
      sclerosis but not in neuroborreliosis. Although other infectious and inflammatory
      diseases cannot be excluded, Lyme disease should be included in the differential
      diagnosis and put forward as being the most likely diagnosis in the appropriate
      clinical setting. Gadopentetate dimeglumine is helpful in assessing the response
      to antibiotic treatment.

PMID- 8570061
TI  - Spinal tumors and subarachnoid hemorrhage: pathogenetic and diagnostic aspects in
      5 cases.
AB  - The authors report 5 cases of spinal tumor associated with subarachnoid
      hemorrhage. Histologically, the tumor was an ependymoma in 2 cases, a neurinoma
      in 2 cases and a hemangioblastoma in 1 case. The pathogenetic and diagnostic
      characteristics of these 5 cases are analyzed in the light of other published
      reports.

PMID- 8570062
TI  - Microvascular decompression in the surgical management of trigeminal neuralgia.
AB  - The pathophysiological mechanisms underlying trigeminal neuralgia are not clearly
      understood and several therapeutic modalities have been advocated. Microvascular
      decompression (MVD) is a widely used surgical approach for the decompression of
      the affected root entry zone (REZ) of the fifth cranial nerve. In this paper, we
      present our experience based on 32 patients with trigeminal neuralgia who were
      treated with MVD, and discuss the role of this procedure in the surgical
      management of trigeminal neuralgia. All patients had typical TN pain and had had
      previous medical management which was unsuccessful. Fourteen patients (44%) had
      been previously treated with other surgical procedures and had persisting pain at
      the time of admission. Preoperatively, computerized tomography was obtained in
      all patients; twelve patients (37.5%) were evaluated with magnetic resonance
      imaging. These neuroradiological studies revealed an asymmetrical vascular
      structure at the involved REZ in nine patients (28%). All patients underwent MVD,
      and a vascular loop causing compression on the REZ of the fifth cranial nerve was
      demonstrated in each case. No mortality was observed, and the only permanent
      morbidity was cerebellar infarction in one patient (3%). Symptoms disappeared in
      all patients in the early postoperative period, and only three recurrences (12%)
      were observed within the follow-up period (mean: 26 months).

PMID- 8570063
TI  - Antibiotic prophylaxis in cerebrospinal fluid shunting: a prospective randomized
      trial in 129 patients.
AB  - The efficacy of a single dose of cefotiam, a cephalosporin of the second
      generation, as prophylaxis for postoperative infection was analyzed in a
      prospective randomized study of 129 patients undergoing cerebrospinal fluid
      shunting. The main focus of interest was the rate of shunt infection requiring
      operative shunt removal. Data were evaluated in the total group and subgroups
      formed for normal and high risk patients, respectively. The overall rate of shunt
      infection was 7.5% in the cefotiam group and 12.9% in the control group. In the
      high risk subgroup infection rate was 14.3% with and 26.3% without cefotiam as
      opposed to 4.3% and 6.9%, respectively, in the normal risk subgroup. Although our
      results do not reach statistical significance, there is a noticeable difference
      of infection rate between those patients who receive the antibiotic and those who
      do not. Therefore, we favor single dose antibiotic prophylaxis in shunting
      procedures.

PMID- 8570064
TI  - Arachnoid cysts: does surgery improve epileptic seizures and headaches?
AB  - During the period from 1985 to 1992 we treated 43 patients with intracranial
      arachnoid cysts (ACs). In this retrospective study we assessed the outcome of
      these patients with regard to non-specific symptoms such as headaches and
      epileptic seizures. Twelve patients had headaches of obscure origin and a mostly
      temporal located AC. Six of these 12 underwent surgery. After the operation 4
      patients (4/6) had no further headaches, two remained unchanged. The other 6
      conservatively treated patients (6/12) had further headaches. Ten of the 43
      patients had epileptic seizures. One patient dropped out of the survey. Six of
      the 9 remaining patients had a temporal AC. Four of these 6 underwent surgery;
      postoperatively the seizure disease of 3 patients (3/6) declined. One patient was
      unchanged. Two patients with epileptic seizures and a temporal AC did not undergo
      surgery and both improved. Three patients with seizures had a convex located AC.
      Two of these 3 underwent surgery. The first patient improved postoperatively, the
      second patient remained unchanged. There was a reduction in the seizures of the
      medically treated patient. It remains ambiguous, whether there is a relationship
      between epileptic seizures and intracranial ACs without obvious intracranial
      pressure signs. A review of the literature, however, showed mostly positive
      results concerning the surgical treatment of ACs under conditions of simultaneous
      epileptic seizures. However, the results largely depend upon the definition of
      the decline of the seizures with regard to the postoperative follow-up, therefore
      we must remain skeptical. Therapy guidelines in the future not only depend on the
      clarification of the pathophysiology of the ACs, but also on a resonable outcome
      examination.

PMID- 8570066
TI  - Ependymoblastoma: a clinical review.
AB  - Ependymoblastoma is a malignant rarely reported neuroectodermal tumor. The
      authors describe a further case of cerebral ependymoblastoma and examine the
      clinical-prognostic aspects of this tumor in the light of the published data.

PMID- 8570065
TI  - Microsurgical management of the lumbar intervertebral disc-disease.
AB  - One hundred consecutive patients operated on for sciatica pain using
      microsurgical techniques between April 1984 and February 1985 were evaluated
      retrospectively. This paper gives preoperative clinical data, end-result of
      surgery, rate of complications and true recurrent herniations. On the basis of
      the results, both soon after operation and at later follow-up (between three and
      five years) we feel encouraged to continue using this mode of operation. Complete
      or significant pain relief was achieved in 92% of patients; 93% were able to
      return to their preoperative normal physical activities. The frequency of
      complications was low.

PMID- 8570067
TI  - Primary brain lymphoma. A brief review of clinical aspects and management.
AB  - Primary C.N.S. lymphoma is a rare tumor. Five such cases were treated in our
      clinic between January, 1991, and October, 1993. Four patients had tumor
      decompression and one had total resection. All of them received radiotherapy
      (radiation dose 40 Gy) and chemotherapy. One patient expired during the immediate
      postoperative period. Four patients showed a disappearance of the tumor on CT
      scan after the complete course of therapy of 9 months. Three patients showed
      recurrence intracranially at 15, 12, and 10 months. All patients died during
      follow up except one, who has been alive without recurrence for 10 months. Median
      survival was 13 months.

PMID- 8570068
TI  - Spontaneous resolution of hypertrophic cranial pachymeningitis.
AB  - A 36-year-old woman presented suffering from severe headache and diploia.
      Magnetic resonance imaging showed a diffuse thickening of the cranial dura mater
      which was enhanced by gadolinium-DTPA. Two months later, an improvement of the
      clinical symptoms and a spontaneous resolution of the dural thickening were
      noted. Hypertrophic cranial pachymeningitis and other diseases causing diffuse
      dural thickening are discussed.

PMID- 8570069
TI  - Giant cholesterol cyst of the petrous bone: a case report.
AB  - The giant cholesterol cyst (GCC) is a benign lesion that gradually enlarges and
      causes progressive bone erosion and serious neurologic deficits of the cranial
      nerves within the temporal bone and jugular foramen. We report here a lesion
      located behind the petrous bone and describe the diagnostic evaluation,
      pathology, and surgical management.

PMID- 8570071
TI  - Priorities in Dialysis. Proceedings of a conference. Vienna, Austria, July 1994.

PMID- 8570072
TI  - Will bone disease still remain one of the most serious complications in dialysis
      patients?

PMID- 8570070
TI  - Spinal cord compression by eosinophilic granuloma of the cervical spine. Case
      report and review of the literature.
AB  - Eosinophilic granuloma is an uncommon lesion, often self-limiting. A location in
      the spine is rare; until now, only 35 cases have been reported. MRI is the most
      effective diagnostic technique, although conventional X-ray can also be useful as
      a first approach. Therapy consists of immobilization of the patients, surgery and
      chemotherapy as required by to the clinical findings of the lesion. The role of
      radiotherapy is still controversial. The authors describe the fourth case of
      eosinophilic granuloma of the cervical spine with neurological symptoms reported
      in literature.

PMID- 8570073
TI  - What do we learn from the European Registry: what will be the underlying problems
      in the year 2000?

PMID- 8570074
TI  - Which treatment for which patient in the future? Possible modifications in CAPD.
AB  - On 578 unselected new patients followed from 1981 through 1993, 51% on CAPD and
      49% on HD, long-term patient and method survivals, cause of death, and drop-out
      in the two methods were compared. Survival, adjusted for patient selection
      biases, was not different on CAPD and HD up to 10 years. 50% of the patients were
      still in their first treatment after 3.5 years on CAPD and after 7 years on HD,
      and 5 and 28% respectively, after 10 years. Patient survival on CAPD was not
      falsely improved by drop-outs. Drop-out is increasing for CAPD, mainly due to
      patient/partner burn-out, which should be relieved by a more liberal application
      of automated PD. Malnutrition is more frequent on CAPD than on HD but not for the
      elderly. In a 3 year prospective study on 60 CAPD and 34 HD patients serum
      albumin, nPCR and nutritional status, as assessed by SGA did not influence
      survival in each modality. Survival was similar with K(p,r)t/V > or = 1.7/week on
      CAPD and Kt/V > or = 1/treatment on HD, and worse below these values. On CAPD, a
      Kp,rt/V > or = 1.96 gave better survivals.

PMID- 8570075
TI  - Balance between pro-inflammatory cytokines and their specific inhibitors in
      patients on dialysis.

PMID- 8570076
TI  - 'Toxicity of glucose: is AGE the answer?'.
AB  - Despite a growing knowledge of the pathogenesis of diabetic nephropathy, the
      increased incidence of end-stage renal disease in diabetic patients continue to
      pose problems of enormous public health and economic importance. Recently, a
      growing body of evidence has linked the accumulation of the late products of
      glucose-protein interaction to a variety of chronic complications, including
      diabetic nephropathy. The formation of irreversible 'advanced glycosylation
      endproducts' resulting from the spontaneous reaction between glucose and proteins
      occurs most noticeably on long-lived structural proteins. In this article, I
      review recent studies suggesting that the pathogenesis of diabetic nephropathy
      leading to end-stage renal disease is caused by the hyperglycaemia-accelerated
      formation of advanced glycosylation endproducts. Recent studies suggest that
      reactive AGE peptides in the circulation potentially play a role as a new version
      of so called 'middle molecules toxic substances'. The evidence is opening a new
      window for our understanding of the pathogenesis of diabetic end-stage renal
      disease and the benefits of various of treatment modalities.

PMID- 8570077
TI  - Treatment of the pre-azotaemic phases of kidney disease in diabetes.

PMID- 8570078
TI  - Hypertension, cardiovascular complications and survival in diabetic patients on
      maintenance haemodialysis.

PMID- 8570080
TI  - Transplantation of the diabetic in 1994. A personal view.
AB  - Kidney transplantation should be tried in all diabetic patients with end stage
      nephropathy, provided there are no definitive contraindications. Pancreas
      transplantation can be tried in singular well defined patients in institutions
      actively involved in adequately related research and development.

PMID- 8570079
TI  - The treatment of the uraemic diabetic. Are we doing enough? A view from Japan.
      Fumitake Gejyo and Collaborate Study Group.
AB  - We evaluated 725 diabetic haemodialysis (HD) patients, inducted into HD from 1967
      to 1993 in Niigata University Hospital and its affiliated hospitals, to clarify
      the relationships among the clinical course and features including diabetes
      mellitus treatment. The glucose metabolism was also studied during HD with
      dialysis fluids containing different glucose concentration. At the time of HD
      induction, diabetic patients showed lower serum creatinine and more frequent
      overhydration, compared with those with glomerulonephritis. Heart failure was the
      leading cause of (53%) among the symptoms as the direct cause of HD induction.
      The survival rate in Japan, particularly in our group, was more prolonged than
      that in USA and Europe. The rate was lower in patients with cardiac complications
      than in those with gastrointestinal problems, and also lower in older patients
      (more than 70 years old) than in younger patients. Among the patients less than
      70 years old, the survival period was longer in patients with serum HbA1c values
      of less than 7.5%, compared to those with greater than 7.5% Cerebro- and cardio
      vascular involvements and infectious diseases were three major causes of death,
      and cerebro- and cardio-vascular disorders and diabetic gangrene were three major
      complications. Serum HbA1c was not different among patients with or without these
      causes of death or complications. In 18.1% of non-insulin-treated NIDDM patients
      insulin was needed one year after HD induction, while 32.1% of insulin-treated
      NIDDM patients before HD induction became free from insulin, who showed body
      weight loss on average of 10 kg. In 33.6% of insulin-treated patients, insulin
      doses increased from 2 to 20 units/day on the non-dialysis day.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8570081
TI  - Renal transplantation in patients with type 2 diabetes mellitus.
AB  - The proportion of type 2 diabetic patients considered for renal transplantation
      has continuously increased over the last decade. Type 2 diabetic patients who
      received a renal allograft had a higher survival rate compared with patients
      maintained on chronic haemodialysis treatment. Diabetic patients with a history
      of myocardial infarction, stroke, or peripheral gangrene before renal
      transplantation had a worse prognosis compared with patients without vascular
      complications. No significant difference of survival was observed between type 1
      and type 2 diabetic patients after renal transplantation. The main causes of
      death were myocardial infarction and septical peripheral gangrene. A history of
      myocardial infarction, stroke, peripheral gangrene is an independent predictor of
      decreased survival in type 2 diabetic patients. Renal transplantation improved
      survival of diabetic patients without vascular complications and should be
      considered as the treatment of choice in this group of patients. However, a
      prospective multicentre study should be initiated to establish guidelines for the
      management of type 2 diabetic patients with end-stage renal disease.

PMID- 8570082
TI  - Management choices in diabetic end-stage renal disease.
AB  - A functioning kidney transplant provides the uraemic diabetic patient a greater
      survival with greater rehabilitation than does either CAPD or maintenance
      haemodialysis. There are no reports, however, of prospective controlled studies
      of dialysis versus kidney transplantation in diabetic patients whose therapy was
      assigned randomly. For the minority ( < 10%) of diabetic ESRD patients who have
      insulin-dependent diabetes mellitus (IDDM), serious consideration should be
      devoted to performance of a combined pancreas and kidney transplant to cure
      diabetes. No matter which ESRD therapy has been elected, optimal rehabilitation
      in diabetic ESRD patients requires that effort be devoted to recognition and
      management of co-morbid conditions. Uraemia therapy, whether CAPD, haemodialysis
      or a kidney transplant should be individualized to the patient's specific medical
      and family circumstances. Attention to control of hypertension and
      hyperlipidaemia may slow the course of macrovascular disease, particularly of the
      coronary arteries, which threatens long-term survival of diabetic kidney
      recipients. Pretransplant cardiac evaluation is mandatory to identify and correct
      silent coronary artery disease that may be severe and life threatening. Survival
      is continuously improving in treating ESRD in diabetes by dialytic therapy, renal
      transplantation, and in IDDM, by combined pancreas and kidney transplantation.
      This inexorable progress in therapy reflects multiple small advances in
      understanding of the pathogenesis of extrarenal micro- and macrovasculopathy in
      an inexorable disease, coupled with safer immunosuppression.

PMID- 8570083
TI  - Learning from the Japanese Registry: how will we prevent long-term complications?
      Niigata Research Programme for beta 2-M Removal Membrane.
AB  - As compared to Europe and USA, the survival rate of chronic haemodialysis (HD)
      patients in Japan is demonstrated by the Japanese Registry to be high. However,
      another Japanese Registry nationwide survey on their quality of life revealed
      serious osteoarticular disorders increasing with the duration of HD. Selecting
      plasma beta2-microglobulin (beta2-M) as a marker, a prospective study on the long
      term clinical effect of a beta2-M-removable membrane (PMMA BK membrane) has been
      performed and the changes in joint pains and plasma beta2-M have been followed
      for 5 years. In addition, the incidence of carpal tunnel syndrome (CTS) and bone
      cysts among 225 patients maintained on HD with BK membrane was analyzed
      retrospectively. By continued use of BK membrane, plasma beta2-M was maintained
      at a significantly lower level than that in HD with conventional cellulosic
      membranes. The total score of joint pain in HD patients treated with BK membrane
      was significantly decreased and maintained at this low value throughout 5 years.
      In HD patients treated with BK membrane for a long period, the occurrence of CTS
      and bone cyst was less and postponed, as compared to patients on HD with
      conventional cellulosic membranes. HD-related amyloidosis had not been observed
      for 5 years in patients treated with BK membrane from the introduction of
      haemodialysis.

PMID- 8570084
TI  - Peripheral nicotine administration increases rubral firing rates in the urethane
      anesthetized rat.
AB  - The presence of cholinergic input to the red nucleus (RN) in the cat is
      demonstrated by choline acetyltransferase (ChAT) staining; however, it is unclear
      what effect this cholinergic input has on neurons of the RN. Further, the
      presence of cholinergic neurons in the rat RN has been the subject of
      controversy. The present study examined the effects of intravenous injections of
      S(-)-nicotine tartrate (62.5-250 micrograms/kg) on the firing rate of rubral
      neurons. Dose-dependent increases in firing rates were observed which were
      blocked by pre-treatment with the nicotinic antagonist, mecamylamine
      hydrochloride. Smaller consistent increases were found after pretreatment with
      62.5 micrograms/kg or 125 micrograms/kg doses of nicotine than were observed
      following the initial administration, suggesting a desensitizing response typical
      of nicotinic receptors.

PMID- 8570086
TI  - Choline acetyltransferase-like immunoreactivity in small diameter neurones of the
      rat dorsal root ganglion.
AB  - In the rat choline acetyltransferase (ChAT)-like immunoreactivity (ChAT-LI) was
      demonstrated in the dorsal root ganglion (DRG), in the superficial spinal cord
      and in the subepithelial layer of the ureter using immunohistochemical
      techniques. In the L1 DRG, 66% of the neurones were ChAT-LI. They did not express
      neurofilament immunoreactivity (RT97 negative) but could also contain calcitonin
      gene-related peptide-like immunoreactivity (CGRP-LI). In the superficial spinal
      cord and in the subepithelial plexus of the ureter--both areas where high numbers
      of fine afferent fibres have been demonstrated--CGRP-LI and ChAT-LI were co
      distributed, indicating that ChAT can be found in the peripheral and central
      endings of small afferents. The data provide morphological evidence that a
      substantial proportion of afferent fibres are cholinergic.

PMID- 8570085
TI  - Calcium-dependent free radical generation in cultured retinal neurons injured by
      kainate.
AB  - Cultured rat retinal neurons exposed to kainate produced free radicals, as
      demonstrated by electron spin resonance (ESR) spin trapping using the nitrone 5,5
      dimethyl-1-pyrroline-N-oxide (DMPO) and the generation of DMPO hydroxyl adduct
      (DMPO-OH). This DMPO-OH production was abolished by EGTA, nitro-arginine and
      oxypurinol, suggesting that it was dependent on Ca2+ influx and subsequent
      activation of nitric oxide synthase and xanthine oxidase. Moreover, kainate
      induced a receptor-mediated Ca2+ influx and neuronal injury assessed by lactate
      dehydrogenase release. Neuroprotection afforded by nitro-arginine and oxypurinol
      shows that calcium-dependent free radical production plays a major role in
      kainate retinal toxicity.

PMID- 8570087
TI  - Sleep deprivation increases brain serotonin turnover in the Djungarian hamster.
AB  - Djungarian hamsters well adapted to a short photoperiod were subjected to 4 h of
      total sleep deprivation (SD) by gentle handling. Tissue concentrations of
      monoamines and of their metabolites were measured from several brain areas using
      HPLC with electrochemical detection. The 5-hydroxyindoleacetic acid/5
      hydroxytryptamine (5-HIAA/5-HT) ratio was significantly increased after SD in the
      hippocampus, hypothalamus and brain stem, indicating increased serotonin (5-HT)
      turnover in those areas, while no changes were found in the frontal cortex and
      olfactory bulb. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC)
      concentrations were elevated in the hypothalamus, while the noradrenaline
      concentrations did not change in any of the measured areas. We conclude that a
      short SD, which has been shown to elevate EEG slow-wave activity during recovery
      sleep, specifically increases 5-HT turnover in the brain.

PMID- 8570088
TI  - Mosaic organization of calcineurin immunoreactivity in the adult cat striatum.
AB  - Calcineurin is a Ca2+/calmodulin-regulated protein phosphatase which is thought
      to play an essential role in the intracellular Ca(2+)-signal transduction. The
      present study showed that calcineurin immunolabeling was differentially
      concentrated in the two distinct compartments showing a mosaic-like pattern in
      the adult cat striatum. The compartment of heightened calcineurin immunolabeling
      corresponded to the extrastriosomal matrix visualized by calbindin-D28K
      immunostaining. Under the light microscope, striatal neurons appeared to be less
      strongly immunoreactive for calcineurin in the striosomes than in the matrix
      compartment. These findings suggest that the novel striatal compartments may
      differ in the intracellular Ca(2+)-signaling cascade associated with protein
      dephosphorylation.

PMID- 8570089
TI  - Detection by 4-parameter microscopic imaging and increase of rare mononuclear
      blood leukocyte types expressing the Fc gamma RIII receptor (CD16) for
      immunoglobulin G in human sporadic amyotrophic lateral sclerosis (ALS).
AB  - By using quantitative multiparameter microscopic imaging we demonstrate
      concentration of two peripheral mononuclear blood leukocyte types expressing the
      Fc gamma RIII receptor for immunoglobulin G in a clinical subgroup of amyotrophic
      lateral sclerosis (ALS, n = 9) showing bulbar palsy (ALSBP) and/or predominant
      involvement of the upper motor neuron (ALSC). Triple fluorescence staining and
      overlay with phase contrast images (4 parameters) reveals that cell type 1 co
      expresses Fc gamma RIII (CD16), CD8 and CD57 surface antigens (ALSC 50 +/- 33.6
      cells/microliters, P = 0.0012; ALSBP 16.5 +/- 32.4, P = 0.029). This cell type is
      not observed in healthy individuals (n = 8) and is only insignificantly increased
      (P > 0.05) in neurological disease controls (stroke, n = 3, 2.1 +/- 3.7;
      polymyositis, n = 6, 1.5 +/- 4.0 cells/microliters) and in ALS cases with
      peripheral symptoms (ALSP n = 12: 7.6 +/- 8.7). Cell type 2 co-expresses Fc gamma
      RIII (CD16) and CD8, but is negative for CD57 (ALSC 60.1 +/- 19.3; ALSBP 24.2 +/-
      28.0 cells/microliters). These findings are consistent with previous reports on
      IgG isotype changes and immune-cell invasion of the motor system in ALS.

PMID- 8570090
TI  - Nitric oxide inhibits depolarization-induced release of endogenous dopamine in
      the rabbit retina.
AB  - The effect of nitric oxide donor compounds (sodium nitroprusside, hydroxylamine
      and S-nitroso-N-acetyl-D,L-penicillamine) on depolarization-induced release of
      endogenous dopamine in the light-adapted, isolated retina of the rabbit was
      studied by HPLC. All three compounds had the same effect, reducing the amount of
      dopamine released by up to 90%. The effect was concentration dependent,
      saturating at 300 microM; it was blocked by the nitric oxide scavenger, mannitol
      (50 mM), which by itself had no effect on the basal release of dopamine. GABAA
      receptors were not involved. Possible cellular mechanisms underlying the findings
      are discussed. It is suggested that the inhibitory interaction between dopamine
      and nitric oxide could represent a higher order function in the light adaptation
      process in the retina.

PMID- 8570091
TI  - Loss of tonic neuronal activity to release L-DOPA in the caudal ventrolateral
      medulla of spontaneously hypertensive rats.
AB  - Experiments were designed to clarify whether a tonic L-DOPA system is altered in
      the caudal ventrolateral medulla (CVLM) of adult spontaneously hypertensive rats
      (SHR), compared to age-matched Wistar-Kyoto rats (WKY). By microdialysis in CVLM,
      basal L-DOPA release was constantly detectable and was lower in SHR than that in
      WKY. This release was reduced by tetrodotoxin perfusion (1 microM) in WKY to a
      basal level in SHR, whereas no modification occurred with tetrodotoxin in SHR. No
      difference of tyrosine hydroxylase and DOPA decarboxylase activities in the CVLM
      region was seen between the two strains. By microinjections into depressor sites
      of CVLM, L-DOPA (10-300 ng) or L-glutamate (3-300 ng) elicited dose-dependent
      depressor and bradycardic responses and greater depressor responses to both amino
      acids were seen at high doses in SHR, compared to WKY. Tonic neuronal activity to
      release L-DOPA is lost in the CVLM of adult SHR and this loss may contribute to
      maintenance of hypertension in SHR.

PMID- 8570092
TI  - Inhibition of NFkB DNA binding activity by glucocorticoids in rat brain.
AB  - The influence of glucocorticoids on the transcription factor NFkB was
      investigated by using the gel mobility shift assay with nuclear extracts prepared
      from rat cerebral cortex and hippocampus after a variety of in vivo treatments.
      Following stimulation with each of three treatments, kainate, pilocarpine, or
      lithium plus pilocarpine-induced seizures, NFkB DNA binding activity was
      significantly greater in the cortex and hippocampus from adrenalectomized than
      from adrenal-intact rats. These results indicate that in rat brain
      glucocorticoids inhibit NFkB activity in addition to the previously reported
      inhibition of the transcription factor AP-1 (activator protein 1). Impairment of
      stimulus-induced transcription factor activity may contribute to the deleterious
      effects of prolonged elevations of glucocorticoids on neuronal function.

PMID- 8570093
TI  - Co-localization of mu-opioid receptor-like and substance P-like
      immunoreactivities in axon terminals within the superficial layers of the
      medullary and spinal dorsal horns of the rat.
AB  - The presence of mu-opioid receptor-like immunoreactivity (MOR-LI) on axon
      terminals was confirmed by light and electron microscopy within the superficial
      layers of the medullary and spinal dorsal horns of the rat. By means of double
      immunofluorescence histochemistry, co-localization of MOR-LI and substance P (SP)
      LI was occasionally observed in axon terminals within the superficial layers of
      the dorsal horns.

PMID- 8570094
TI  - Prostaglandin-dependent c-Fos expression in the median preoptic nucleus of pigs
      subjected to restraint: correlation with hyperthermia.
AB  - Restraint using a nose snare activates the hypothalamo-pituitary-adrenocortical
      axis and induces c-Fos expression in the paraventricular hypothalamus in the pre
      pubertal pig; this procedure also induces hyperthermia in pigs. To investigate
      the neural mechanisms involved in this thermoregulatory response, c-Fos protein
      was quantified in the forebrains of pigs snared for 15 min (n = 5), injected with
      saline vehicle via an i.v. catheter (controls, n = 4) or treated with the
      cyclooxygenase inhibitor, indomethacin (2 mg/kg i.v.), prior to a 15 min period
      of snaring (n = 3). There were few c-Fos immunopositive nuclei in the median
      preoptic nucleus of non-stressed animals. By contrast, c-Fos expression in this
      region was enhanced by snaring (P < 0.001) and this response was markedly reduced
      (P < 0.002) by indomethacin. The results suggest that restraint induces a
      prostaglandin-mediated increase in core temperature (stress hyperthermia) in the
      growing pig that involves the activation of preoptic thermoregulatory neurons.

PMID- 8570095
TI  - Independent regulation of primary dendritic and axonal growth by maturing
      astrocytes in vitro.
AB  - Whereas axon growth is limited in the mature mammalian central nervous system
      (CNS), dendritic remodeling occurs throughout life. Since glia can regulate
      neurite growth during development, we tested whether glia from the mature CNS
      differ in their ability to support axon and dendrite growth. Cortical neurons
      were co-cultured with neonatal or mature astroglial, and dendrite and axon
      outgrowth quantified after 5DIV using immunohistochemical techniques. Primary
      dendritic growth was supported equally well by mature and immature astrocytes. By
      contrast, mature astrocytes demonstrated a reduced ability to support axon
      growth. We propose that the independent regulation of axon and dendrite growth by
      astrocytes provides a means by which the mature nervous system may adjust its
      function to activity and the environment.

PMID- 8570096
TI  - Amino-terminal region of the beta-amyloid precursor protein activates mitogen
      activated protein kinase.
AB  - The secreted form of the beta-amyloid precursor protein (beta-APP) has previously
      been shown to stimulate mitogen-activated protein (MAP) kinases in PC-12
      pheochromocytoma cells. The amino-terminal half of secreted beta-APP contains a
      region rich in cysteine residues reminiscent of cysteine-rich binding regions in
      other families of extracellular proteins. We found that reductive alkylation of
      disulfide linkages eliminated the ability of secreted beta-APP to activate MAP
      kinase. To confirm the role of the cysteine-rich amino-terminal region, fragments
      representing the amino- and carboxyl-terminal halves of secreted beta-APP were
      expressed in bacteria as fusion proteins and purified. Ten-minute treatment with
      the amino-terminal segment of beta-APP activated MAP kinase approximately 15
      fold, while the carboxyl segment had no effect. The amino-terminal fragment, like
      intact secreted beta-APP, was substantially inactivated by reduction of
      sulfhydryl groups. These results suggest that the amino-terminal region of beta
      APP is responsible for activation of MAP kinase and that it requires structural
      loops created by disulfide linkages for activity.

PMID- 8570097
TI  - Short-term changes of finger representation at the somatosensory cortex in
      humans.
AB  - The present study describes short-term modifications of the representation of the
      fingers at the cortex. Somatosensory evoked potentials were stimulated at the
      1st, 3rd and 5th finger, and at the 1st and 5th fingers after anaesthesia of the
      2nd, 3rd and 4th fingers. Somatotropic arrangement of the fingers was determined
      by dipole localization. After local anaesthesia significant changes of the 1st
      finger to lateral and of the 5th fingers to medial were found. Injection of the
      anaesthetic drug caused predominant burning pain at the basis of the fingers,
      suspected to result in a 'hyperactivation' of the connected somatosensory cortex,
      and giving rise to a shift of the locations towards the neighbouring cortex. This
      replicates results in animal studies, believed to be caused by an alteration of
      the excitatory-inhibitory balance at the somatosensory cortex.

PMID- 8570098
TI  - A comparison of the N-terminal sequence of the leech Theromyzon tessulatum
      angiotensin converting-like enzyme with forms of vertebrate angiotensin
      converting enzymes.
AB  - This paper reports the purification of an angiotensing-converting like enzyme
      (ACE) of ca. 120 kDa from extracts of head membranes of the leech Theromyzon
      tessulatum. After solubilization with Triton X-114, the ACE-like enzyme contained
      in the detergent-poor fraction was separated using five steps of purification
      including gel permeation and anion exchange chromatographies followed by reverse
      phase HPLC. The first 23 amino acid residues of the N-terminal part
      (GLDPELSPGCFSADEAGAQLFAE) of the purified S-pyridylethylated leech ACE
      established by automated Edman degradation revealed ca. 87% sequence identity
      with the N-terminal sequence of the guinea pig ACE. This enzyme cleaves the
      hyppuryl-His-Leu substrate with a specific activity of 5600 nmol hyppurate min-1
      mg protein-1. Hydrolysis of this substrate by ACE-like enzyme is inhibited at 80%
      by 10 microM captopril or 10 microM lisinopril (IC50 of 200 nM and 50 nM,
      respectively). This enzyme is close in sequence and in activity to single domain
      vertebrate ACE. This is the first N-terminal sequence of an ACE-like enzyme
      determined in invertebrates.

PMID- 8570099
TI  - Sustained response of pineal melatonin synthesis to a single one-minute light
      pulse during night in Djungarian hamsters (Phodopus sungorus).
AB  - Previous experiments have demonstrated that short light pulses during the night
      suppress pineal melatonin formation almost completely for the remainder of the
      night. Here, the effects of a single 1 min light pulse during the night on
      melatonin synthesis during the following night was investigated in Djungarian
      hamsters (Phodopus sungorus). It is shown that the melatonin pattern during the
      consecutive night is suppressed to a greater extent than that caused by acute
      light exposure, indicating a very effective light memory of the melatonin
      generating neuronal network, possibly a key to understanding the reliability of
      the photoperiod-measuring system.

PMID- 8570100
TI  - Changes in dural thickness reflect changes in intracranial pressure in dogs.
AB  - The thickness of the dura mater was obtained from ultrasound probes on the skull
      and fast Fourier transform-Cepstrum through a probability process at various
      intracranial pressures (ICP), measured with pressure transducers, in 12
      anesthetized dogs. There was a constant relationship between changes in thickness
      (micron) and changes in ICP (mmHg) from 5 to 80 mmHg. The estimated thickness at
      0 mmHg of pressure and values obtained from measurements of dural samples were
      very similar. Our method provides estimations of ICP, and holds promise for
      measuring thicknesses below 1000 microns in biological systems in general.

PMID- 8570101
TI  - Pressor responses to distension of the ureter in anaesthetised rats:
      characterisation of a model of acute visceral pain.
AB  - We have characterised pressor responses to stimulation of the ureter in
      anaesthetised rats (n = 20) as a model of acute visceral pain. The left ureter
      was cannulated close to the bladder and graded stimuli applied (5-90 mmHg, 30 s).
      The threshold was approximately 25 mmHg. Suprathreshold pressures evoked
      responses proportional to the stimulus intensity, which were little altered when
      stimulation of the kidney was prevented by ligation of the ureteric-pelvic
      junction. The stimulus response curve was dose-dependently attenuated by morphine
      (1-3 mg kg-1 i.v.), in a naloxone reversible manner. The characteristics of the
      responses observed correlate well with pain sensation in man and with the
      properties of ureteric primary afferent neurones in animals.

PMID- 8570102
TI  - One hundred years of radiation therapy: a tribute.
AB  - The history of radiation therapy is fascinating and tragic. As we celebrate the
      centennial of Wilhelm Roentgen's discovery, physicians should remember the
      pioneers who made it possible for contemporary radiation oncologists to practice
      with the highest degree of sophistication.

PMID- 8570103
TI  - The discoverer of x-rays: Wilhelm Conrad Roentgen.
AB  - "Immortal is his work. Immortal his name." This dedication to Wilhelm Roentgen,
      the discoverer of x-rays, is much deserved. As a meticulous scientist, Roentgen
      devised and repaired all the apparatus needed for his experiments, and he did
      most of the work himself.

PMID- 8570104
TI  - New Jersey radiology: the first decade.
AB  - Within months of Roentgen's discovery of x-rays, physicians were anxious to learn
      about the new technology. The Transactions of MSNJ kept practitioners informed
      about the applications and the dangers of medical radiology. The author looks
      back at the first decade of radiology in New Jersey.

PMID- 8570105
TI  - New Jersey's Thomas Edison and the fluoroscope.
AB  - Thomas Edison played a major role in the development of early x-ray technology in
      1896, notably increasing tube power and reliability and making the fluoroscope a
      practical instrument. Eventually, Edison would move x-ray technology from the
      laboratory to the marketplace.

PMID- 8570106
TI  - The early years of radiology in New Jersey: an interview with C. Richard
      Weinberg, MD. Interview by Barbara Smith Irwin.
AB  - C. Richard Weinberg, MD, began his career in 1941 at Newark Beth Israel Hospital.
      Dr. Weinberg was interviewed in an oral history project documenting the history
      of radiology in New Jersey. Dr. Weinberg's recollections provide a first-hand
      look at the changes in radiology.

PMID- 8570107
TI  - A brief economic history of radiology.
AB  - The authors present a historical review of radiology reimbursement, including the
      effects of health care legislation and court decisions. The political leadership
      of the American College of Radiology is detailed. Changes in the delivery of
      health care will alter the practice of medicine.

PMID- 8570108
TI  - Health service use of ionizing radiations. NHS Executive Health Service.

PMID- 8570109
TI  - The use of 99Tcm-Technegas in the investigation of patients with pulmonary
      thromboembolism.
AB  - Pulmonary embolism remains a major cause of morbidity and mortality, being
      responsible for an estimated 200,000 deaths per annum in the USA and 21,000 per
      annum in the UK. Lung scintigraphy is in many instances the investigation of
      choice in suspected pulmonary thromboembolism. A normal perfusion lung scan
      excludes pulmonary embolism. An abnormal perfusion scan, while being sensitive,
      is of low specificity for the diagnosis of pulmonary embolism and needs to be
      complemented with a ventilation study. Lung ventilation has been studied using
      inert gases of radiolabelled aerosols. The new radiopharmaceutical 99Tcm
      Technegas is a suspension of 99Tcm-labelled, ultrafine, carbon particles produced
      in an atmosphere of high-purity argon. The size of the particles is of the order
      of 0.005-0.2 microns, which assures good peripheral penetration and alveolar
      deposition. After inhalation, static images in multiple projections may be
      acquired. The resultant images are of excellent technical quality and several
      publications have shown the value of Technegas images as an adjunct to perfusion
      imaging in suspected pulmonary thromboembolism. Studies comparing Technegas
      images with other ventilatory radiopharmaceuticals have in the majority of
      instances reported comparable diagnostic qualities.

PMID- 8570110
TI  - Immediate 201Tl reinjection: an alternative approach in myocardial perfusion
      scintigraphy? A comparison with contrast angiographic findings.
AB  - Thallium-201 (201Tl) stress-redistribution/reinjection imaging provides a
      reliable diagnostic approach in patients evaluated for myocardial ischaemia.
      Immediate reinjection of 201Tl after completing the stress images followed by
      imaging 1 h later shortens the investigation time to 2.5 h and may provide a
      novel approach. In this study, we validated the immediate reinjection approach in
      the assessment of myocardial perfusion and viability using contrast angiographic
      findings as the reference standard. We studied 114 patients with documented
      cardiac catheterization data using quantitative planar 201Tl stress/immediate
      reinjection imaging. The 201Tl findings were compared with contrast angiographic
      data, coronary arteriographic findings and electrocardiographic data. Myocardial
      regions were considered to be viable if they (1) showed normal or hypokinetic
      wall motion, (2) were supplied by patent coronary arteries or by occluded
      arteries with adequate collateral circulation, or (3) were not related to
      electrocardiographic infarct site. Myocardial regions were considered to be non
      viable if they (1) showed akinetic or dyskinetic wall motion, (2) were supplied
      by occluded vessels with inadequate collateral circulation, or (3) were related
      to electrocardiographic infarct site. Of 280 regions with normal or hypokinetic
      wall motion, 47 (17%) regions showed persistent 201Tl defects compared with 21 of
      26 (81%) regions with akinetic/dyskinetic wall motion (P < 0.0001). Of 318
      regions supplied by patent vessels, 65 (20%) regions showed persistent 201Tl
      defects compared with 14 of 22 (64%) regions subtended by occluded vessels (P <
      0.0001). When the 201Tl findings were compared with electrocardiographic infarct
      site, 37 of 259 (14%) remote regions showed persistent defects compared with 42
      of 83 (51%) infarct-related regions (P < 0.0001). We conclude that persistent
      defects on 201Tl immediate reinjection images are significantly more often
      associated with severe left ventricular wall motion abnormalities, coronary
      artery occlusion and infarct-related regions. In particular, agreement between
      the wall motion approach and scintigraphic findings was excellent, with 21 of 26
      akinetic or dyskinetic segments showing persistent defects and 233 of 280 normal
      or hypokinetic segments measured as viable by the reinjection technique,
      resulting in a sensitivity of 81%, a specificity of 83% and an overall accuracy
      of 83%. These findings show the potential of immediate 201Tl reinjection imaging
      for assessing myocardial perfusion and viability.

PMID- 8570112
TI  - A radionuclide study of regional gastric motility.
AB  - The aims of this research were to study some methodological aspects of
      radionuclide methods for assessing regional gastric motility and to determine the
      parameters that can be extracted along with their normal values or patterns.
      During the lag phase, the antral contraction curve showed three different
      patterns. At the beginning, the antral activity was too low to be analysed.
      Irregular variation of the count rate was then observed, followed by a more
      regular contraction. The application of Fourier transformation to the well
      defined cyclical count rate variations revealed two areas with high amplitude
      values but with phase opposition. No peristaltic wave could be identified. After
      the lag phase, the antral curve showed cyclical variations of count rates with a
      frequency of about three cycles per minute. Slightly displaced curves but with a
      much lower amplitude were observed at different parts of the stomach. Several
      factors were found to influence the antral contraction curve, including the
      choice of region of interest and time since the last meal. Irregularities in the
      antral curve, both in terms of frequency and of amplitude, were not unusual in
      healthy subjects. These should be taken into account when interpreting antral
      contraction curves. The phase image showed a well-defined peristaltic contraction
      pattern. Three 360 degrees cycles were usually observed throughout the stomach,
      suggesting that the time necessary for a peristaltic wave to sweep through from
      the upper part of the stomach to the antrum is about 1 min. Similar phase images
      were obtained in all subjects regardless of the amount of time since the meal
      containing the radioactive tracer, suggesting that gastric peristalsis can easily
      be assessed and interpreted. The amplitude image showed high amplitude in the
      antral area and in the greater curvature of the stomach. In the lesser curvature,
      the amplitude was much lower. Unlike the phase image, however, there was marked
      variability in the regional amplitude distribution. The value of the regional
      amplitude distribution for evaluating regional gastric motility is therefore
      limited.

PMID- 8570111
TI  - Usefulness of dipyridamole-thallium imaging in 257 patients with atherosclerotic
      vascular disease.
AB  - We evaluated the usefulness of dipyridamole-thallium imaging for the detection of
      ischaemic heart disease in 257 patients with atherosclerotic vascular disease (80
      patients with arteriosclerosis obliterans, 81 patients with aneurysm of the
      abdominal aorta, 60 patients with aneurysm of the thoracic aorta and 36 patients
      with dissecting aortic aneurysm). Clinical evidence of ischaemic heart disease
      was found in 69 of 257 (27%) patients, including 32 patients with
      arteriosclerosis obliterans, 23 with aneurysm of the abdominal aorta, 9 with
      aneurysm of the thoracic aorta and 5 with dissecting aortic aneurysm.
      Dipyridamole-thallium imaging identified myocardial ischaemia in 49 of 69 (71%)
      patients with clinical evidence of ischaemic heart disease. Dipyridamole-thallium
      imaging showed positive results in 67 of 81 (83%) patients with aneurysm of the
      abdominal aorta. In patients with no clinical evidence of ischaemic heart
      disease, the results of dipyridamole-thallium imaging were positive in 39 of 188
      (21%) patients. Dipyridamole-thallium imaging was positive in 90 of the 257 (35%)
      patients as a whole. When we combined the patients with positive dipyridamole
      thallium imaging with those with negative dipyridamole-thallium imaging but who
      had clinical evidence of ischaemic heart disease, 42% of all patients had
      evidence of ischaemic heart disease. Our findings suggest that atherosclerotic
      vascular disease is strongly associated with ischaemic heart disease and that
      dipyridamole-thallium imaging is useful for the detection of ischaemic heart
      disease.

PMID- 8570113
TI  - The aetiology of solitary hot spots in the ribs on planar bone scans.
AB  - The aim of this study was to determine the aetiology of solitary hot spots in the
      ribs found at bone scintigraphy in patients with known extraskeletal malignancy.
      A group of 34 patients whose bone scans showed a solitary hot spot in a rib were
      identified retrospectively over a 4-year period. They all had a known
      extraskeletal malignancy. Aetiology of the rib hot spot was established in 26
      patients based on a review of clinical features, radiographic findings and
      clinical follow-up. In eight cases it remained indeterminate. In 14 (41%) cases,
      the rib lesion was malignant in origin, 9 were due to metastasis and 5 due to
      direct spread from intrapulmonary malignancy. In 12 (35%) cases, it was benign.
      In the remaining 8 (24%) cases, the aetiology was indeterminate. In the subgroup
      of 14 hot spots confined to the anterior rib end, 5 (36%) were due to malignancy,
      4 (28%) were benign and 5 (36%) were indeterminate. We conclude that solitary hot
      spots in the ribs of patients with known extraskeletal malignancy undergoing bone
      scintigraphy are frequently (41%) malignant in origin. This also applies when the
      hot spot is in the anterior rib end (36% malignant). Thus, such hot spots are far
      more sinister than previously reported and require careful clinical and
      radiographic evaluation.

PMID- 8570114
TI  - Immunoscintigraphy with a 99Tcm-labelled anti-granulocyte monoclonal antibody in
      patients with human immunodeficiency virus infection and AIDS.
AB  - The value of immunoscintigraphy with technetium-99m (99Tcm) labelled anti
      granulocyte monoclonal antibody (BW250/183) was studied prospectively in human
      immunodeficiency virus (HIV-1) antibody-positive patients presenting with fever
      without localizing symptoms or signs. Twenty-three studies were performed in 23
      patients and the results of 99Tcm-anti-granulocyte imaging were compared with the
      definitive microbiological or cytological diagnosis. Twenty-one patients had an
      infective cause of pyrexia, one patient had disseminated lymphoma and one Kaposi
      sarcoma. 99Tcm-anti-granulocyte antibody imaging correctly identified the sites
      of infection in only five (24%) patients, four of whom had infective colitis (one
      also had bacterial pneumonia) and one of whom had cellulitis. Sixteen foci of
      infection were not localized by 99Tcm-anti-granulocyte immunoscintigraphy (false
      negative scans). Six of these patients had Pneumocystis carinii pneumonia; other
      diagnoses in this group included bacterial or fungal pneumonia and bacteraemia
      secondary to line infections. 99Tcm-anti-granulocyte antibody did not accumulate
      in the patients with disseminated lymphoma and Kaposi sarcoma (true-negative
      scans). 99Tcm-anti-granulocyte imaging, therefore, appears useful in identifying
      extrathoracic infection in HIV-1 positive patients. Its lack of sensitivity for
      the identification of pulmonary infection means that its role in the
      investigation of HIV-1 antibody-positive patients with fever without localizing
      symptoms or signs is limited.

PMID- 8570115
TI  - Evaluation of 99Tcm-labelled human immunoglobulin in animal models of
      experimentally induced inflammatory lesions.
AB  - Human immunoglobulin (HIG) was labelled with 99Tcm using different Sn-ligand
      (methylene diphosphonate, MDP) in high yields. The effect of Sn:ligand ratios and
      protein (HIG) on the biodistribution pattern of 99Tcm-HIG in an animal model of
      turpentine-induced inflammatory lesions was studied. 99Tcm-HIG was excreted
      predominantly via the renal pathway. The use of higher amounts of MDP and HIG
      resulted in relatively slower blood clearance and increased uptake of 99Tcm-HIG
      in various organs. Also, higher amounts of ligand [Sn:MDP (1:5)] resulted in
      significantly greater bone uptake (P < 0.001), while protein caused slower blood
      clearance and greater liver uptake. Despite the increased uptake of tracer in
      various organs, the ratio of inflamed:normal muscle uptake did not change
      significantly. A scintigraphic study was carried out with both 99Tcm-HIG and
      99Tcm labelled with human serum albumin (HSA) in turpentine-induced inflammatory
      lesions produced in rabbits. The study revealed no significant differences in
      uptake early on, but the target:non-target ratio was higher with 99Tcm-HIG at 24
      h. 99Tcm-HIG also had superior characteristics compared with 99Tcm-HSA.

PMID- 8570117
TI  - An improved imaging agent for malignant melanoma, based on [Nle4,D-Phe7]alpha
      melanocyte stimulating hormone.
AB  - Two compounds have been synthesized based on [Nle4,D-Phe7]alpha-melanocyte
      stimulating hormone (NDP-MSH) in which either one or two peptide sequences were
      covalently linked through their N'-termini to a single molecule of
      diethylenetriamine pentaacetic acid (DTPA). These two compounds (monoNDP-MSH-DTPA
      and bisNDP-MSH-DTPA, respectively) bound indium-111 (111In) stably and showed
      hormonal activity as great or greater than alpha-melanocyte stimulating hormone
      (alpha-MSH). Both compounds were able to target 111In to Cloudman S91 melanomas
      in DBA2 mice. MonoNDP-MSH-DTPA gave the highest tumour:blood and tumour:tissue
      ratios and showed least unspecific radioactivity in the liver and kidney.
      Radioscintigraphy of mice showed good tumour localization of 111In with both
      compounds, clear images being obtainable within 2 h of injection. Scans with
      monoNDP-MSH-DTPA showed some kidney and thyroid but no liver radioactivity,
      whereas bisNDP-MSH-DTPA gave extensive abdominal radioactivity, most of which was
      associated with the liver and kidneys. MonoNDP-MSH-DTPA was cleared from the
      tumour much less rapidly and gave more favourable tumour:blood ratios than other
      alpha-MSH derivatives previously investigated. It is concluded that monoNDP-MSH
      DTPA offers promise as a melanoma imaging agent in man.

PMID- 8570116
TI  - Humoral anti-OV-TL 3 response after the intravenous administration of
      radiolabelled Fab' or F(ab')2 fragments in ovarian cancer patients.
AB  - The human anti-mouse antibody (HAMA) response was determined in the serum of
      patients suspected of having ovarian cancer who underwent radioimmunoscintigraphy
      with either 99Tcm-OV-TL 3 Fab' (n = 20) or 111In-DTPA-OV-TL 3 F(ab')2 (n = 73).
      Blood samples were collected prior to and at several time points post-intravenous
      injection. The detection of HAMA was performed with an in-house OV-TL 3 F(ab')2
      based sandwich-type immunoradiometric assay (IRMA). The homologous IRMA
      demonstrated that 8 of 20 (40%) patients had developed HAMA responses after
      injection of Fab' fragments and that 14 of 73 (19%) patients had developed HAMA
      responses after F(ab')2 administration. The subclass of the measured HAMA was
      analysed in a limited number of samples, showing IgG or IgM as well as mixed
      responses. The kinetics of the HAMA responses varied greatly. Our study showed
      the relevance of the sampling time and frequency: HAMA responses can be easily
      underestimated with a low sampling frequency. The homologous IRMA described in
      this study was able to quantify the OV-TL 3-specific HAMA responses. With
      additional assays, the subclass of the HAMA could be further analysed.
      Remarkably, the fraction of HAMA responders after injection of OV-TL 3 Fab'
      fragments was in the same range as the proportion of HAMA responders after
      F(ab')2 administration.

PMID- 8570119
TI  - Molds, fungi cause sick building syndrome.

PMID- 8570118
TI  - Dynamic hepatic scintigraphy in colorectal cancer.
AB  - The clinical usefulness of the hepatic perfusion index (HPI) at the time of
      presentation has been evaluated in patients with colorectal cancer. In 83
      consecutive patients, the HPI was abnormally elevated in 34 of 37 (93%) patients
      with overt metastases. This study confirms that the HPI is elevated in most
      patients with overt hepatic metastases. Long-term follow-up of patients with
      abnormal HPI and no obvious liver metastases is continuing.

PMID- 8570120
TI  - A 10-point exhaust ventilation management standard.

PMID- 8570121
TI  - Evaluating surface contamination at hazardous waste sites.

PMID- 8570122
TI  - Back belts pay off for nurses.

PMID- 8570123
TI  - Association of tumor cell proliferation with lymph node metastasis in early
      gastric cancer.
AB  - Recently, many studies have reported on the relationship between malignant
      potential of neoplasms and cell proliferation. Proliferating cell nuclear antigen
      (PCNA) is an auxiliary protein of DNA polymerase delta and is considered to
      correlate with the cell's proliferative state. In this study, we investigated the
      correlation between tumor cell proliferation and nodal status of early gastric
      carcinoma. One hundred two endoscopically biopsied specimens from patients with
      early gastric carcinoma prior to operation were investigated by an
      immunohistochemical study, using anti-PCNA monoclonal antibody. Correlation of
      PCNA labeling index (percentage of positive cells per over 500 tumor cells) with
      nodal status were studied. PCNA labeling index in patients with lymph node
      metastasis was significantly higher in those without metastasis. Moreover,
      multivariate analysis indicated that PCNA labeling index is an independent
      significant factor for lymph node metastasis. As a result of this study, PCNA
      labeling index was suggested to be effective as one of the predictors of lymph
      node metastasis.

PMID- 8570124
TI  - Expression of pS2 estrogen-inducible protein in primary breast cancer.
AB  - The expression of pS2 estrogen-inducible protein was investigated using formalin
      fixed, paraffin-embedded sections from 210 primary breast cancers. One hundred
      and three (49%) out of 210 cases were positive for pS2. A significant correlation
      existed between pS2 expression and hormone receptor status. Patients with pS2
      expression had better overall survival and a longer survival time after the first
      recurrence than those without pS2 expression. By multivariate analysis, pS2 was
      not an independent prognostic indicator, but pS2 expression was a possible
      indicator for responsiveness to treatment in relapsed breast cancer patients.

PMID- 8570126
TI  - Effects of cisplatin on cell cycle kinetics, morphological change, and cleavage
      pattern of DNA in two human ovarian carcinoma cell lines.
AB  - We evaluated the effects of cisplatin on the cell kinetics, cytomorphological
      changes, and cleavage patterns of DNA in two lines of human ovarian carcinoma
      cells. KF-1 cells displayed a cell cycle arrest in the G2M phase, while HMG cells
      displayed a transient cell accumulation in the S phase, without obvious G2M
      arrest. Morphological changes characterized by condensation and fragmentation of
      chromatin, and DNA cleavage by oligonucleosome-sized DNA fragments were observed
      in the HMG cells but not in the KF-1 cells. The pattern of cell death in HMG
      cells was considered to be apoptosis, but that of KF-1 cells necrosis. These
      findings showed the different mechanisms of anti-tumor effect of cisplatin on
      human ovarian carcinoma cell lines, including cell kinetics and pattern of cell
      death.

PMID- 8570125
TI  - Vinorelbine and mitomycin C in anthracycline-pretreated patients with advanced
      breast cancer.
AB  - At present, there is no satisfactory treatment for advanced breast cancer
      patients who have become refractory to anthracyclines. Vinca alkaloids and
      mitomycin C (MMC) are among the drugs most frequently used in this setting.
      Recently, vinorelbine (VNR) has been reported to be highly active in advanced
      breast cancer. Sixty advanced breast cancer patients previously treated with
      anthracyclines have been exposed to VNR 25 mg/m2 i.v. on days 1 and 8, and MMC 10
      mg/m2 i.v. on day 1, with cycles repeated every 4 weeks. There were 3 complete
      and 21 partial responses for an overall response rate of 40% (CI 95%: 28-52%).
      Median duration of response and median survival were 7 and 10 months,
      respectively. Myelosuppression was the dose-limiting toxicity, but it was
      generally mild to moderate. Although this combination appears to be effective and
      well tolerated, every effort should be made to further improve treatment results
      in anthracycline-pretreated advanced breast cancer.

PMID- 8570127
TI  - Effect of methotrexate on the intracellular phosphoribosyl pyrophosphate level
      and glucose transport of Ehrlich ascites tumor cells in vitro.
AB  - Methotrexate (MTX) suppressed the growth of Ehrlich ascites tumor (EAT) cells in
      vitro. The intracellular level of phosphoribosyl 5-pyrophosphate (PRPP) of EAT
      cells increased in a dose-dependent manner in response to MTX treatment. At the
      same time, the rate of glucose transport was lowered. Hypoxanthine reversed both
      these effects of MTX and partially rescued EAT cell growth. Under all conditions
      tested, changes in rate of glucose transport were shown to be the result of
      alterations in the number of glucose transporter (Vmax) rather than ligand
      affinity (Km). The dual action of MTX as a chemotherapeutic agent is discussed in
      this light.

PMID- 8570128
TI  - Augmentation of antitumor efficacy by the combination of actinomycin D with tumor
      necrosis factor-alpha and interferon-gamma on a melanoma model in mice.
AB  - The efficacy of combination treatment with actinomycin D (Act D), recombinant
      human tumor necrosis factor-alpha (TNF-alpha), and recombinant murine interferon
      gamma (IFN-gamma) was examined on established MmB16 melanoma in mice. TNF-alpha
      alone had marginal effect in vitro on melanoma cells. However, when this cytokine
      was combined with either Act D or IFN-gamma, synergistic cytostatic/cytotoxic
      effects were observed. The highest cytotoxicity was demonstrated in cultures of
      melanoma cells in which all three agents together were added. In mice inoculated
      with 10(6) melanoma cells (into the footpad of the hind limb) and treated locally
      with Act D, TNF-alpha and IFN-gamma, beneficial therapeutic effects were found.
      When initiated 1 week after tumor cell inoculation, the 7-day treatment with all
      these agents administered together at daily doses: 0.2 microgram (Act D), 1
      microgram (TNF-alpha), and 200 U (IFN-gamma) resulted in a significant delay of
      tumor progression in comparison to the therapy that included either Act D alone
      or TNF-alpha in combination with IFN-gamma. Side effects of such a treatment,
      both local and systemic, were negligible. The results of this study demonstrate
      that combination of regional chemotherapy (actinomycin D) and immunotherapy (TNF
      alpha/IFN-gamma) may display higher efficacy than either treatment alone and may
      increase therapeutic index without augmenting toxic effects.

PMID- 8570129
TI  - Improving survival of medulloblastoma: results in two groups of patients.
AB  - This retrospective study compares the results obtained in 56 children with
      medulloblastoma treated with two different protocols at our center between 1975
      and 1990. Since 1985 we have been enrolled in the medulloblastoma SIOP II
      protocol in which we have entered 27 patients. These patients from the SIOP group
      (SG) and the 29 children treated before 1985, the historical group (HG). When the
      two groups were compared for age and sex distribution, no differences were found;
      however, prognostic factors were worse in the HG than in SG: 21 versus 15 T3-T4
      and 13 versus 8 high-risk, respectively. The relapse rate was 63% for the HG and
      39% for the SG. Five-year disease-free survival was 31% for the HG and 56% for
      the SG (p = 0.037). Five-year survival was 52 and 70%, respectively (p = 0.055).
      When SG and HG were compared by stratifying for tumor size, surgical resection
      and the risk variable, better disease-free survival was obtained in SG than in
      HG. In a multivariate analysis, the HG and the high-risk proved to be variable
      independent predictors of poor survival. We observe an increase in survival in
      our patients with medulloblastoma.

PMID- 8570131
TI  - Extended resections of ductal pancreatic cancer--impact on operative risk and
      prognosis.
AB  - 114 patients received a standard and 75 patients an extended resection of ductal
      pancreatic carcinoma at the Hanover Medical School, Germany, from 1971 until
      1993. Standard pancreatic resections were combined with vascular resection and
      reconstruction in 46 and additional organ resections in 45 cases. Vascular
      resections affected the mesentericoportal vein in 37, the common hepatic in 10
      and the superior mesenteric artery in 7 cases. Pancreas resections were combined
      with total gastrectomy in 23, partial colectomy in 17, hemihepatectomy in 14,
      adrenalectomy in 8 and nephrectomy in 5 patients. Curative resections could be
      accomplished in 86% of patients without and 81% with extended resections.
      Additional vascular resections neither increased the operative risk nor
      deteriorated the long-term prognosis after resection. Additional organ
      resections, however, significantly increased the risk of lethality and impaired
      the long-term prognosis. Especially resections of synchronous hepatic metastases
      and colectomies were associated with a poor survival probability.

PMID- 8570130
TI  - Increased survival time in brain glioblastomas by a radioneuroendocrine strategy
      with radiotherapy plus melatonin compared to radiotherapy alone.
AB  - The prognosis of brain glioblastoma is still very poor and the median survival
      time is generally less than 6 months. At present, no chemotherapy has appeared to
      influence its prognosis. On the other hand, recent advances in brain tumor
      biology have suggested that brain tumor growth is at least in part under a
      neuroendocrine control, mainly realized by opioid peptides and pineal substances.
      On this basis, we evaluated the influence of a concomitant administration of the
      pineal hormone melatonin (MLT) in patients with glioblastoma treated with radical
      or adjuvant radiotherapy (RT). The study included 30 patients with glioblastoma,
      who were randomized to receive RT alone (60 Gy) or RT plus MLT (20 mg/daily
      orally) until disease progression. Both the survival curve and the percent of
      survival at 1 year were significantly higher in patients treated with RT plus MLT
      than in those receiving RT alone (6/14 vs. 1/16). Moreover, RT or steroid therapy
      related toxicities were lower in patients concomitantly treated with MLT. This
      preliminary study suggests that a radioneuroendocrine approach with RT plus the
      pineal hormone MLT may prolong the survival time and improve the quality of life
      of patients affected by glioblastoma.

PMID- 8570132
TI  - Doxifluridine as palliative treatment in advanced gastric and pancreatic cancer
      patients.
AB  - BACKGROUND: The association of 5-fluorouracil (5-FU) and leucovorin is currently
      the most used combination in the treatment of advanced gastrointestinal
      neoplasms. Doxifluridine (d-FUR) is a fluoropyrimidine derivative that is
      converted into 5-FU inside tumor cells, where it is selectively cytotoxic. The
      oral administration of dFUR has been extensively investigated in colorectal
      carcinoma, and has been proven to be active and well tolerated. The purpose of
      this study was to test the effectiveness of the oral combination with dFUR plus l
      leucovorin in gastric and pancreatic cancer patients. METHODS: A total of 50
      cases were treated with l-leucovorin 25 mg, followed 2 h later by d-FUR 1,200
      mg/m2 for 5 days; the cycles were repeated every 10 days. The regimen was given
      for a maximum of 36 cycles or until disease progression. Twenty-six patients had
      gastric cancer (all of whom were pretreated with polychemotherapy) and 24 had
      advanced pancreatic carcinoma. RESULTS: Objective responses were obtained in 4
      (15%; 95% Cl 1-29) patients with gastric cancer, and in 1 (4%) with pancreatic
      cancer. The median response duration was 4 months. All of the responses were seen
      in patients previously treated with 5-FU-containing regimens. The median survival
      in gastric cancer patients was 7 months. Toxicity was moderate: WHO grade III and
      IV diarrhea was observed in 14% of the cases. CONCLUSIONS: This study indicates
      the efficacy of oral d-FUR plus l-leucovorin as palliative treatment in gastric
      cancer patients. The results in pancreatic carcinoma are disappointing but are in
      line with the published data relating to fluoropyrimidines.

PMID- 8570133
TI  - Combination of 5-fluorouracil, adriamycin, ifosfamide and cisplatin in metastatic
      adult soft tissue sarcoma: results of a phase II study.
AB  - Treatment results of advanced soft tissue sarcomas are still suboptimal. To
      evaluate the clinical effects of a combination therapy (FADIP) with Adriamycin
      (ADM), ifosfamide (IFO), cisplatin (DDP) plus continuous infusion of 5
      fluorouracil (FU) as a synergistic factor for alkylating agents, a phase II study
      was initiated in patients with advanced soft tissue sarcomas of different
      histological subtypes. Fifty-six previously untreated patients with advanced soft
      tissue sarcomas of different histological subtypes (24 females, 31 males, median
      age 51.3 years, median Karnofsky performance status 80%) were included in this
      study. Treatment consisted of ADM 50 mg/m2 i.v. on day 1, IFO 4,000 mg/m2 i.v. on
      day 1, mesna 800 mg/m2 i.v. 3 x with 8-hour intervals on day 1 starting with IFO
      administration, FU 500 mg/m2 i.v. as 24-hour infusion on days 1 + 2, DDP 100
      mg/m2 i.v. on day 2. This regimen was repeated every 4 weeks for at least 2
      cycles. Major WHO grade III/IV hematological toxicity was observed in 35/56
      patients. One toxic death due to severe neutropenia and fungal pneumonia
      occurred. Granulocyte colony-stimulating factor was administered in 8/35
      neutropenic patients. Time to recovery was significantly reduced and no
      infectious complication was observed. WHO grade III/IV toxic diarrhea was
      observed in 8 patients requiring intravenous fluid replacement. WHO grade III/IV
      nausea occurred in 11 patients, 9/11 responded to symptomatic treatment with
      ondansetron alone. The overall response rate was 30.3%. The median duration of
      response (complete/partial response, CR/PR) was 18.1 months, the median
      progression-free interval was 4.5 months. The median survival time of all
      patients was 11.8 months, and 18.1 months in responding patients (CR/PR). Tumor
      related pain was effectively reduced in 15/31 patients under treatment. FADIP
      produces comparable response rates to other standard treatment regimens in soft
      tissue sarcomas. Prolonged duration of response and median survival may be due to
      the use of continuous infusion of FU as a synergistic factor to alkylating
      agents. Granulocyte colony-stimulating factor is effective in reducing the
      otherwise observed high rate of WHO grade III/IV hematological toxicity with
      severe neutropenia.

PMID- 8570134
TI  - Immunohistochemical detection of Bcl-2 protein in small cell carcinomas.
AB  - The expression of Bcl-2 protein in 29 small cell carcinomas (SCCs; 6 surgical and
      15 biopsy specimens obtained from various organs, 7 metastatic lymph nodes, and 1
      metastatic liver tissue) was investigated by immunohistochemical technique.
      Negative staining was observed in only two cases (7%). The majority of Bcl-2
      positive tumors had > 95% positive cells, with a moderate staining intensity. A
      combined small-cell lung cancer showed discordant staining results between two
      different histology types. No correlations of Bcl-2 immunoreactivity with p53
      expression and clinical staging were found. Our findings suggest that Bcl-2
      expression may play a certain role in the early phases of SCC tumorigenesis, or
      that it may solely be a succeeding property directly derived from the tumor
      progenitor cells. As the Bcl-2 protein was present in most cases, it is not a
      useful prognostic or treatment marker for the cancer.

PMID- 8570135
TI  - Feasibility study on protracted infusional 5-fluorouracil and consecutive low
      dose cisplatin for advanced gastric cancer.
AB  - In this phase II trial 31 patients with advanced gastric cancer (21 with
      metastatic cancer and 10 with locally advanced cancer) were treated with a
      continuous 24-hour infusion of 5-fluorouracil (5-FU) 330 mg/m2/day plus low-dose
      cisplatin (CDDP) 6 mg/m2/day by bolus infusion on days 1-5. The regimen with a
      combination of 5-FU and low-dose CDDP (FLDP) was repeated weekly for two to four
      courses according to response and tolerance. In 24 (77%) of the 31 patients, four
      courses of this regimen were administered. The overall response rate was in 14/31
      (45%) patients with measurable disease, including one complete response and 13
      partial responses. An especially high response rate of 60% was seen in 10
      patients with liver metastasis. Median survival time was 11 months (range 6-27+)
      in the 10 cases of locally advanced cancer and 11 months (range 6-24+) in the 21
      cases of metastatic cancer. Toxicity was primarily hematologic. Leukopenia and
      thrombocytopenia of World Health Organization (WHO) grade 3 or 4 occurred in 4/31
      (13%) and 4/31 (13%) of patients, respectively. Renal dysfunction, which is a
      major toxicity associated with CDDP, was not observed without hydration. The
      patients were able to eat during therapy and preserved a good quality of life. A
      randomized trial including the FLDP regimen is needed to compare it with other
      active regimens, particularly the use of high-dose CDDP.

PMID- 8570136
TI  - Interaction of cis-diamminedichloro-platinum(II) and its analogues cis-1,1-
      cyclobutanedicarboxylato(2R)-2-methyl-1,4-butanediammineplatinum(II) and cis
      diammine(glycolato)platinum with hyperthermia in vivo.
AB  - The interaction of cis-1,1-cyclobutanedicarboxylato(2R)-2-methyl-1,4-
      butanediammineplatinum(II) (NK121) and cis-diammine(glycolato)platinum(II) (254
      S), analogues of cis-diamminedichloroplatinum(II) (CDDP), with hyperthermia was
      examined in vivo. Antitumor activity of the platinum complexes at the maximum
      tolerated dose (MTD) with or without hyperthermia was evaluated by the tumor
      growth delay assay using B16F10 melanoma growing in the legs of C57BL/6J mice.
      MTD of CDDP, NK121 or 254-S at the single intraperitoneal injection with
      hyperthermia was 8, 50 or 30 mg/kg, respectively. Treatment of the tumor-bearing
      limb at 43 degrees C for 30 min resulted in a tumor growth delay of 1.1 days. A
      single dose of CDDP produced a 3.3-day tumor growth delay. When CDDP was injected
      just before hyperthermia (43 degrees C, 30 min), the growth delay increased to
      5.5 days (1.7-fold increase). With NK121, there was a 1.5-day growth delay. In
      combination with hyperthermia, the tumor growth delay by NK121 was 3.2 days (2.1
      fold increase). Injection of 254-S led to a growth delay of 3.5 days, and this
      delay was extended to 5.7 days (1.6-fold increase) when combined with
      hyperthermia. Changes in serum blood urea nitrogen (BUN) were determined 5 days
      after intraperitoneal drug administration with or without hyperthermia. A single
      administration of CDDP 8 mg/kg resulted in an elevated BUN level, and this was
      enhanced in combination with hyperthermia (66.3 mg/dl, 2.7-fold over control).
      NK121 50 mg/kg at 37 degrees C did not result in elevation of BUN, but mild
      nephrotoxicity was noted in combination with hyperthermia (40.3 mg/dl, 1.6-fold
      increase over control). The administration of 254-S 30 mg/kg resulted in an
      elevated BUN level, and this elevation was enhanced in combination with
      hyperthermia (48.6 mg/dl, 2.0-fold increase over control). Our data showed that
      NK121 and 254-S as well as CDDP produced greater tumor growth delay together with
      hyperthermia than did the drug alone. Though these new compounds were designed
      with reduced nephrotoxicity, attention should be paid to increased nephrotoxicity
      when combined with hyperthermia.

PMID- 8570137
TI  - Evaluation of late nephrotoxicity in long-term survivors of Hodgkin's disease.
AB  - Chemotherapy (Ctx) and/or radiotherapy (Rtx) are effective in the treatment of
      Hodgkin's disease (HD) but potentially involve late toxicities, including
      nephrotoxic side effects. Therefore a follow-up study has been performed to
      screen patients for late signs of an impaired tubular or glomerular function and
      to correlate data of renal function with type of therapy and cumulative doses of
      cytotoxic agents applied. 81 patients in complete remission for at least 2 years
      and a median follow-up of 96 (39-304) months, and 53 controls were examined.
      Clinical routine parameters such as creatinine and electrolytes were determined.
      A differentiation of proteinuria into the albumin, high molecular weight (HMW)
      and low molecular weight (LMW) fractions made it possible to assess glomerular
      and tubular function based on the LMW/HMW ratio. The structural protein
      fibronectin served as an additional, sensitive marker of glomerular integrity.
      Routine parameters of kidney function did not show any signs of late
      nephrotoxicity. However, patients treated for HD had a higher ratio of LMW/HMW in
      comparison to the group of healthy volunteers (p < 0.01), indicating subclinical
      tubular renal damage. When the cutoff for tubular damage was defined as LMW/HMW >
      1.5, 50% of the patients treated with combined modality, and 42 and 37% of the
      patients with Ctx or Rtx alone had subclinical tubular alterations, respectively.
      A tendency towards a higher prevalence of subclinical tubular changes was
      observed in patients with higher cumulative doses of methotrexate or ifosfamide
      and in patients with combined Ctx and Rtx with radiation fields involving the
      renal area. Changes in glomerular function were not observed. It is concluded
      that treatment of HD is not associated with clinically apparent long-term
      impairment of renal function but can lead to subclinical alterations. Further
      clinical implications of these subclinical tubular alterations cannot be assessed
      at present. A differentiation of proteinuria does not have to be performed
      routinely but might be useful in the follow-up of selected patients with an
      increased risk.

PMID- 8570139
TI  - Morphometric analysis of neurons in ganglia: geniculate, submandibular, cervical
      spinal and superior cervical.
AB  - The geniculate ganglia (GG), the submandibular ganglion (SG), the cervical spinal
      ganglion (CSG) and the superior cervical ganglion (SCG) are clinically important.
      But details of these ganglia have not been included in textbook descriptions. We
      conducted research to bring precise figures to light. We prepared serial sections
      of these ganglia in five Japanese adults after precise dissections to count the
      numbers, measure the perimeters and the areas, and calculate the circularity
      ratios (CRs) of the ganglion cells. The numbers of neurons were in the following
      order: SCG > CSG > SG > GG, and the average neuronal areas in the following
      order: CSG > GG > SG > SCG. Average neuronal CRs were around 0.90 in all ganglia.
      In other words, the morphometric evaluation showed that neurons in such ganglia
      are practically circular in shape. Our morphometry thus reveals that the neurons
      in these ganglia are sensory neurons in the broad definition of the word from a
      quantitative point of view.

PMID- 8570138
TI  - Different expression of nm23-H1 and nm23-H2 protein with proliferative activities
      in various sizes of human renal cell carcinoma.
AB  - Ninety-five paraffin blocks of renal cell carcinomas (RCCs) and background normal
      tissue were obtained from patients in Nara Medical University Hospital and used
      for studying silver-binding nucleolar organizer regions (AgNORs), proliferating
      cell nuclear antigen (PCNA) and nm23 oncogenes. The RCCs were grouped by size (<
      or = 30, > 30 and < or = 50, > 50 mm of average diameter) and grade according to
      the General Rules for Clinical and Pathological Studies of Renal Cell Carcinoma,
      Japan. Numbers of cases were 17 in the < or = 30-mm group, 36 in the > 30- and <
      or = 50-mm group, and 42 in the > 50-mm group. AgNOR scores were 4.68 +/- 1.22,
      3.91 +/- 1.31 and 3.01 +/- 1.05, respectively, with significant intergroup
      differences. Frequencies of PCNA-positive cells per 500 cells were 33.8 +/- 23.5,
      39.4 +/- 13.8 and 45.9 +/- 38.8. nm23-H1 immunohistochemical staining proved
      strongly positive in 21 of 24 areas of normal proximal convoluted tubules, 4 of 8
      dysplasia cases, 2 of 17 in the < or = 30-mm group RCCs, 1 of 36 in the > 30- and
      < or = 50-mm group RCCs and none of 42 in the > 50-mm RCCs. nm23-H2 in contrast
      was weakly positive in 3/24, 2/8, 12/17, 30/36 and 20/42 of the cases,
      respectively. The results indicated an inverse relationship between tumor size
      and score of AgNOR without any variation in PCNA labeling and contrasting
      expression of nm23-H1 and nm23-H2 linked to the size of RCCs.

PMID- 8570140
TI  - Distribution of the macromolecular components of masticatory muscles during
      differentiation of the muscle fibers in the postnatal rat.
AB  - The distribution of collagen fibers of rat masticatory muscles during the
      postnatal period (two weeks), was investigated by electrophoresis and
      immunohistochemistry. At these stages, the myosin of rat masticatory muscles
      displays specific electrophoretic patterns. Comparison of the myosin patterns of
      these muscles allows their identification. 1) Analysis by SDS-PAGE indicated that
      one of three weakly reactive stainable proteins with lower mobility than the
      heavy chain of myosin disappeared from the temporal muscle on day 13, as compared
      with other masticatory muscles. However, in histochemical analysis of the muscle
      fibers, the reaction specific for succinic dehydrogenase (SDH) activity was
      strong, and the fibers on day 13 could be classified into two types with respect
      to SDH activity. By contrast, on day 0, the fibers were classified into two types
      with respect to myosin ATPase activity. 2) Immunohistochemical analysis indicated
      that the distribution of the components of the extracellular matrix in the
      epimysium (type I collagen), perimysium (type I collagen, fibronectin, and
      laminin) and endomysium (type III collagen, fibronectin, laminin, and tenascin)
      was related to the metabolic capacity on days 12 to 13. The variability in the
      types of myosin and in proteins of the extracellular matrix might be important
      during the development of rat masticatory muscles.

PMID- 8570141
TI  - Uptake of horseradish peroxidase (HRP) by the urinary bladder epithelial cells of
      several mammalian species.
AB  - Transitional epithelium of mammalian urinary bladder is a functional barrier
      which prevents passage of urine into the submucosa. In a previous study, we found
      uptake by the epithelial cells of horseradish peroxidase (HRP) instilled into the
      mouse bladder lumen. In the present study, the ability of bladder epithelial
      cells to take up HRP, which was visualized by the diaminobenzidine (DAB)
      reaction, was compared among several mammalian species by light and electron
      microscopy. In mouse, rabbit and dog bladder, the superficial cells of the
      transitional epithelium showed positive reactions for HRP, while cells in lower
      epithelial layers were DAB-negative. Some of the reaction products could be seen
      as a number of granules not surrounded by a membrane. The intercellular space of
      the epithelium was DAB-negative. In rat and guinea pig bladder, however, all
      urothelial cells showed negative reactions for HRP indicating that no uptake of
      HRP had been occurred in these animals. These results indicate that the uptake of
      HRP by the superficial cells of the bladder epithelium differs among mammalian
      species, indicating some functional differences in their superficial cells.

PMID- 8570142
TI  - Immunohistochemical investigations of parvalbumin localization in the skeletal
      muscle fibers of rats.
AB  - Parvalbumin (PA) is a water soluble, low-molecular weight, calcium-binding
      protein which has been thought to be involved in the relaxation of skeletal
      muscle fibers. Although it is well known that PA concentrations are higher in
      fast twitch fiber than slow twitch fiber, the localization of PA within the
      cytoplasm of single muscle fibers is still unknown. The present study, therefore,
      was undertaken to clarify the PA localization by immunohistochemical methods
      using the confocal laser scanning microscope (CLSM) and transmission electron
      microscope (TEM). Wistar strain male rats were fixed by vascular perfusion with
      4% paraformaldehyde solution, and the extensor digitorm longus muscle was
      dissected out. For fluorescent antibody examination, these specimens were quickly
      frozen in melting isopentan and sections were cut using a cryostat at -25 degrees
      C. These sections were incubated in anti-PA and anti-Troponin (TR) respectively,
      and then exposed to Texas-Red- and FITC-labelled secondary antibodies. For TEM
      study, the pre-embedding method was used. Fluorescent immunohistochemical study
      has clearly shown that both PA and TR are located intimately in the I-band of the
      skeletal muscle fibers. The finding by the immunofluorescent study correlated
      well with those which have been seen at the ultrastructural level. The fact that
      PA is located in close proximity to TR is considered to be very reasonable when
      we consider it in terms of the muscular contraction-relaxation cycle.

PMID- 8570143
TI  - Immunolocalization of 91 kDa ascitic protein in the human placenta.
AB  - A 91 kDa protein, sharing antigenicity with a pregnancy-associated antigen, was
      isolated from the ascitic fluid of a patient suffered from the gynaecological
      malignant neoplasms. It was revealed in the human placenta by immunocytochemical
      techniques, and found to be localized in the stroma, including a fibrous network,
      fibroblasts and the Hofbauer cells of the terminal and stem villi in the first
      trimester. Immunoreactive staining was also found in macrophage-like cells,
      presumable the precursor of the Hofbauer cell, in the stem villi of placenta. It
      is assumed that macrophage-like cells containing the protein would be originated
      from the extraembryonic mesoderm or blood vessels, and then migrated to the
      stroma of terminal villi. During the second trimester, the protein was observed
      in numerous vesicles among the syncytial trophoblasts. The density of these
      immunoreactive vesicles and the cytoplasm of Hofbauer cells was rapidly increased
      with gestational stages, whereas it was gradually reduced towards the late-second
      trimester. The highest labellings occurred at around 17 weeks or later. On the
      other hand, at term, the protein was mainly observed in numerous villous blood
      vessels including endothelial cells. In the light of these results, a hypothesis
      concerning mechanisms of transplacental permeability of the protein by the
      placental barrier is discussed further.

PMID- 8570144
TI  - [Simultaneous registration of VECP and pattern ERG during artificially raised
      intraocular pressure].
AB  - The visual evoked cortical potentials (VECP) are changed by the artificial
      increase in intraocular pressure (IOP). The exact location of the damage is still
      unclear. One possibility is that the increased ocular pressure reduces the blood
      flow in the optic nerve head. The function of the optic nerve fiber function
      would be decreased by this effect. Another possibility is that the generation of
      the signals in the retinal ganglion cells could be influenced by the artificial
      pressure enhancement. We developed a method of simultaneous recording pattern
      reversal electroretinograms (PERG) and VECP during artificially raised IOP. The
      PERG was recorded by cutaneous electrodes (Grass, USA; diameter 5 mm), which were
      positioned close to the lid margins. The pattern reversal rate was 7.9
      reversals/s. In a pilot study, we examined 10 healthy volunteers with
      artificially increased ocular pressure. In 9 cases, amplitudes showed a more
      stable behavior in the VECP than in the PERG: the mathematical behavior of the
      amplitude/pressure curves was more stable in the VECP of 6 volunteers and once in
      the PERG. Signs of very sufficient autoregulation could be found in the VECP of 7
      volunteers and once in the PERG. The critical pressure, at which a further
      increase in IOP causes a continuous amplitude decrease to the noise level, was 9
      times more stable in VECP (median 53 mmHg) than in PERG (median 48 mmHg). The
      results lead to the conclusion that in healthy persons the artificial pressure
      rise influences the ganglion cells at an earlier timepoint than the signal
      transmission in the axons.

PMID- 8570145
TI  - Early detection of inborn dyschromatopsias in preschoolers and young
      schoolchildren.
AB  - Color vision is one of the most important factors of human vision. Early
      detection of color vision malfunction in children is of utmost importance,
      allowing parents and teachers to take appropriate and timely measures for
      children's future professional orientation. A cohort of 300 children aged 4-6
      years (49-86 months) were examined by color vision testing and divided into three
      age groups of 4-5, 5-6 and > 6 years. Their ability to name the fundamental
      spectral colors and read Ishihara's pseudoisochromatic plates were recorded. The
      results obtained are presented in tables and figures. Data analysis showed the
      youngest group of children to be unsuitable for such testing of color vision.
      Numerical data revealed considerable percentage deviations as compared to the
      older groups. In addition, a great difference between the girls and boys
      indicated psychomotor development to be much faster in girls of that age.
      Generally, data obtained by the distribution of the results for the two older age
      groups were consistent with those found in the literature; thus, the authors
      propose an early examination for the detection of inborn chromatopsia to be
      performed in preschool children, but not before the age of five. Ishihara's
      pseudoisochromatic test can be useful in differentiating between dyschromatic and
      other children, but it is very difficult to implement for singling out
      dyschromates according to the protan or deutan type.

PMID- 8570146
TI  - Capillary macroaneurysms in central retinal vein occlusion.
AB  - The occurrence of macroaneurysms as a consequence of central retinal vein
      occlusion was previously reported in one study only with the appearance of a
      single capillary macroaneurysm. We report a case of central retinal vein
      occlusion presenting several capillary macroaneurysms. It may be supposed that
      retinal ischemia plays an important role in the pathogenesis of capillary
      macroaneurysms, in association with the pressure increase in the capillary
      network due to venous obstruction.

PMID- 8570147
TI  - Mild retinal changes in a 47-year-old patient with phytanic acid storage disease.
AB  - A 47-year-old man complained of poor near vision. He had chronic polyneuropathy,
      bilateral shortening of the proximal phalanges, and ichthyosis. His serum
      phytanic acid level was merkedly elevated. The fundus and fluorescein angiograms
      showed diffuse fine granular changes throughout the retina. However, no
      pigmentary retinal degeneration, vessel attenuation, or disk atrophy was found.
      The visual field and dark adaptation results were normal. The electroretinogram
      demonstrated mildly subnormal rod responses with normal implicit times and cone
      responses within the normal range. The S-cone electroretinogram showed decreased
      amplitude and normal implicit time. These ophthalmological findings were not
      consistent with classical retinitis pigmentosa. We believe that this patient may
      have an uncommon type of adult Refsum's disease.

PMID- 8570148
TI  - Clinical features of episcleritis and scleritis in some Japanese patients.
AB  - We retrospectively examined 52 patients (60 eyes) with episcleritis and
      scleritis. Their mean ages were 57 and 47 years, respectively. Slight female
      predominance was noted. Most patients had unilateral involvement. The ocular
      symptoms at the initial visit were redness and ocular pain. Some eyes with
      scleritis were complicated with uveitis, corneal lesions, and elevated
      intraocular pressure. In most affected eyes, corticosteroid eyedrops alone
      resolved the disease. We believe that in addition to ophthalmological
      examinations, standard physical and specific laboratory investigations should be
      performed in patients with episcleritis and scleritis.

PMID- 8570149
TI  - Cytomegalovirus optic neuritis: characteristics, therapy and survival.
AB  - Little is known about the natural history of cytomegalovirus (CMV) optic neuritis
      in the acquired immunodeficiency syndrome. We analyzed the clinical course of CMV
      optic neuritis in 30 consecutive subjects (35 eyes), and compared the survival of
      patients with CMV optic neuritis to that of a group having CMV retinitis alone,
      with both groups matched for ganciclovir therapy. Four untreated eyes had a
      median final visual acuity of no light perception. The median final visual acuity
      was 20/100 in treated subjects with a mean follow-up of 6.6 months. Following
      ganciclovir treatment, 2 eyes showed visual improvement, 17 eyes had unchanged
      visual acuity, and 12 eyes had marked drop in acuity. Relapse occurred in 4
      subjects maintained on single-dose ganciclovir, and was controlled on double-dose
      ganciclovir. Survival was similar in the group of CMV retinitis alone versus the
      group of CMV optic neuritis with retinitis. Early recognition and therapy of CMV
      optic neuritis protects against irreversible visual loss. CMV optic neuritis does
      not carry a worse prognosis for survival than CMV retinitis alone.

PMID- 8570150
TI  - Effects of calcium antagonists in the treatment of ophthalmic postherpetic
      neuralgia.
AB  - Postherpetic neuralgia is one of the most common, but also one of the most
      difficult conditions to treat. This condition mainly involves trigeminal,
      intercostal and sciatic nerves and the brachial plexus area. It mostly appears in
      patients older than 60 years. Although pain is a transient condition, the pain of
      postherpeutic neuralgia may become intractable, disabling an may decrease the
      quality of the patient's life. We studied 30 patients affected by ophthalmic
      postherpetic neuralgia, appearing, some months after fronto-orbital cutaneous
      eruption. All patients received nicardipine retard, decreasing gradually, 40
      mg/day for 2 weeks. The monitoring of pain was performed using the visual
      analogue score of Scott-Huskissonn. The results show an improvement in 'pain
      relief'.

PMID- 8570151
TI  - Cataract extraction comparative study of ocular Behcet's disease and idiopathic
      uveitis.
AB  - A retrospective clinical trial was performed to review the management and discuss
      the outcome of cataract extraction in eyes with complicated cataract due to
      ocular Behcet's disease (BD) (n = 55) and idiopathic uveitis (IU) (n = 43). The
      aim was to find the best method of treatment in each pathology. The surgical
      methods were intracapsular cataract extraction (ICCE), extracapsular cataract
      extraction (ECCE), ECCE + intraocular lens (ECCE + IOL), and ECCE +
      trabeculectomy (ECCE + T). The postoperative visual prognosis was found to be
      significantly worse in eyes with ocular BD, than in those with IU because of the
      severe posterior segment complications of ocular BD, particularly optic atrophy
      (p < 0.05). When the outcome was evaluated with regard to the individual surgical
      techniques, the prognosis was found to be significantly better in eyes with IU
      undergoing ECCE than in those with BD undergoing the same operation (p < 0.05).
      No significant differences were observed between the groups with regard to the
      other surgical treatment modalities (p < 0.05).

PMID- 8570152
TI  - Measurement of rabbit intraocular pressure with the Tono-Pen.
AB  - A Tono-Pen-1 (TP-1) and a Tono-Pen-2 (TP-2) were calibrated against direct
      manometry in the eyes of living rabbits to determine the accuracy of the Tono
      Pen. Eighteen normal eyes of 10 rabbits were cannulated and connected to a
      pressure transducer with a chart recorder. Intraocular pressure (IOP) was
      increased from 5 to 40 mm Hg in 5-mm-Hg increments and from 40 to 80 mm Hg in 10
      mm-Hg increments. After each incremental increase, IOP was measured first with a
      TP-1 and then with a TP-2. Plotting the mean Tono-Pen readings for each eye
      against the transducer pressure produced the following two regression line
      formulas: y = -0.613+0.790x (r2 = 0.97) for TP-1, and y = -1.45+0.824x (r2 =
      0.97) for TP-2. Neither regression line was statistically different; p = 0.2 for
      the two slopes, and p = 0.24 for the y-axis intersection. The TP-1 and TP-2 can
      be used to rapidly and accurately measure the IOP in normal rabbit eyes. Tono-Pen
      readings do, however, significantly underestimate pressures in the range of 5-80
      mm Hg. A table with 95% confidence intervals for corrected IOP readings obtained
      with the TP-1 or -2 is provided.

PMID- 8570153
TI  - Keratoconus and progressive cone dystrophy.
AB  - A 33-year-old woman had keratoconus and retinal cone dystrophy, an association
      that has not been reported previously. The family history suggested a recessive
      inheritance pattern. Genetic probes for these conditions are needed to determine
      whether the coincidental occurrence of keratoconus and cone dystrophy is due to a
      genetic relationship or was a chance event.

PMID- 8570154
TI  - Sebaceous carcinoma responds to radiation therapy.
AB  - We describe a patient with an eyelid tumor that responded well to radiation
      therapy. The histopathological diagnosis was poorly differentiated sebaceous
      carcinoma. The patient received 52 Gy electron beam irradiation in a 5-week
      period; thereafter, the tumor diminished. The histopathological findings after
      radiation showed that most tumor cells underwent massive necrosis with hyalinized
      obstructive vessels. The tumor was under control at the 9-month follow-up
      examination.

PMID- 8570155
TI  - Diffuse choroidal hemangioma: report of a clinicopathological study in a 4-year
      old boy.
AB  - The authors examined the clinicopathologic features of a 4-year-old boy with a
      diffuse choroidal hemangioma, yet without any features of the Sturge-Weber
      syndrome. The tumor occurred as a grayish intraocular mass with an overlying
      retinal detachment and was highly reflective in the ultrasonic examination. After
      contrast, the CT scan revealed diffuse thickening of the ocular wall associated
      with an enhanced irregular orbital mass. The pathologic examination revealed a
      cavernous hemangioma involving the entire choroid with extrascleral extension.
      Diffuse choroidal hemangioma occurring in childhood and unrelated to the Sturge
      Weber syndrome is a rare condition that should be included in the differential
      diagnosis of retinoblastoma.

PMID- 8570156
TI  - Recurrent subconjunctival hemorrhages in patients with Fuchs' heterochromic
      iridocyclitis.
AB  - We examined two women who had keratic precipitates, minimal intracameral cells
      and flare, diffuse iris stromal atrophy, posterior subcapsular cataract, and
      vitreous opacities in their left eyes. No ocular pain, photophobia, or posterior
      synechia was noted. Their right irises appeared brown. Heterochromia was evident
      in both patients. Recurrent subconjunctival hemorrhages were also in their
      affected left eyes. It is possible that subconjunctival hemorrhages in our
      patients may be associated with Fuchs' heterochromic iridocyclitis.

PMID- 8570157
TI  - Magnetic resonance imaging in the early diagnosis of cavernous sinus thrombosis.
AB  - A 55-year-old man reported a severe headache of 3 days' duration, left ptosis and
      left lid swelling before examination. The ocular examination revealed left eye
      proptosis, severe edema of the left bulbar conjunctiva and lid, increasing
      intraocular pressure of the left eye and ptosis on the left side with decreased
      extraocular movement. The right eye was normal. Hematologic studies indicated
      mild inflammation. An enhanced computed tomography scan revealed proptosis of the
      left globe and enlargement of the superior ophthalmic vein and cavernous sinus of
      the left side. Angiography revealed an area of interrupted blood flow in the left
      cavernous sinus. Enhanced magnetic resonance imaging (MRI) with Gd-DTPA revealed
      a low-intensity area that was suspected to be a blood clot in the enlarged left
      cavernous sinus. This case indicates the efficacy of enhanced MRI examination in
      the early diagnosis of cavernous sinus thrombosis.

PMID- 8570158
TI  - Comment on the paper of L. Casellato:.

PMID- 8570159
TI  - How predictable are the results of excimer laser photorefractive keratectomy? A
      review.
AB  - At the close of 1994, the AOA News reported that at least 14 companies were
      preparing to market equipment for excimer laser photorefractive keratectomy
      (PRK). More than a dozen PRK centers had been formed for the purpose of
      recruiting optometrists to co-manage PRK patients. Because the surgery is a "no
      touch" computer-driven procedure whose duration is measured in seconds, the
      preoperative and postoperative care of PRK patients will assume major importance.
      Optometrists who will be asked to take part in the management of PRK patients
      must be able to counsel patients on matters such as the predictability of the
      procedure in terms of postoperative refractive error and visual acuity, as well
      as the possibility of unintended consequences such as difficulty in night
      driving. Information currently available, mainly as a result of studies conducted
      in other countries, shows that the results of PRK are highly predictable for
      preoperative myopia up to about -3.00 D and somewhat less predictable for myopia
      between -3.00 and -6.00 D, whereas for myopia greater than -6.00 D the
      probability of achieving a full correction decreases rapidly with increasing
      amounts of myopia. As compared to radial keratotomy (RK) in which the
      postoperative refractive error drifts relentlessly in the hyperopic direction,
      PRK brings about an initial hyperopic shift followed by regression leading to
      increasing myopia. Researchers disagree on the cause of the postoperative
      hyperopic shift and regression, and on the value of various methods of
      controlling regression including the use of wider and deeper ablation profiles
      and the postoperative use of corticosteroids and nonsteroid anti-inflammatory
      drugs. It is too early to determine whether the myopic creep in PRK will be as
      persistent as the hyperopic creep in RK, but it is likely that whereas presbyopic
      post-RK patients may have adequate distance vision but require corrective lenses
      for reading, presbyopic post-PRK patients may be sufficiently myopic to require
      lenses for distance vision but not for reading.

PMID- 8570160
TI  - Effect of age on tear osmolality.
AB  - Certain aspects of tear physiology change with age (reflex secretion and
      stability), whereas others remain unchanged (tear volume, evaporation rate, basal
      tear production). To establish the variation in tear osmolality with age, 0.2 to
      0.4 microliter samples were collected from 50 normal males and 50 normal females
      (age range 17 to 75 years). Nanoliter aliquots of the samples were analyzed by
      freezing point depression nanoliter osmometry. Mean tear osmolality for the whole
      group was 303.6 +/- 13.0 mOsm/kg and was not significantly affected by age (r2 =
      0.014, p = 0.378). For males the mean was 307.1 +/- 14.4 and for females 300.1 +/
      10.4 mOsm/kg, a significant gender difference (p = 0.006). Males under age 41
      had tear osmolality which was not significantly different from that of males over
      41 years of age (307.7 +/- 15.6 and 305.7 +/- 11.5 mOsm/kg, respectively, p =
      0.671) but the mean tear osmolality for females under age 41 years (297.6 +/-
      11.2 mOsm/kg) was significantly different from that of older females (304.8 +/-
      6.7 mOsm/kg, p = 0.017). There was no significant correlation between age and
      osmolality for males (r2 = 0.003, p = 0.699), but there was a significant
      correlation for females (r2 = 0.159, p = 0.004). Males under age 41 years have a
      significantly higher mean tear osmolality than females under 41 years of age (p =
      0.003). The age and gender differences found for tear osmolality can be accounted
      for by the low values in young females, which may be related to the increased
      tear flow observed in young females. A reduction in this high flow rate to a more
      "normal" level in older females may account for the rise in tear osmolality to a
      level which is not significantly different from that of older males. Generally in
      normal eyes, the osmolality of tears remains within normal limits and is not
      affected by age.

PMID- 8570162
TI  - A systems model for low vision rehabilitation. I. Basic concepts.
AB  - The basic concepts and structure of a hierarchical systems model for low vision
      rehabilitation is developed and presented. The model is built on the assumption
      that the patient has a desired life state, which is not realized because of the
      visual impairment. Life state is defined as a set of activities that the
      individual wants or needs to perform. The activities that constitute life state
      are represented hierarchically in a system called the activity breakdown
      structure (ABS). The highest level of the ABS represents the objectives served by
      the activities (e.g., daily living, vocational, recreational, social, and
      educational objectives). Under each objective is a set of goals and serve that
      objective. Any goal could serve multiple objectives. The requirements for
      successfully achieving a goal may vary with the objective that goal serves. The
      lowest level of the ABS consists of tasks that must be performed successfully to
      achieve particular goals. Any task could serve multiple goals. Each goal and each
      task has a value to the patient (i.e., level of importance) and also is
      associated with a level of difficulty. The need for rehabilitation, which is
      captured in the formal construct rehabilitative demand, for each goal and its
      subsidiary tasks, scales with the value of the goal or task and with the
      difficulty in achieving the goal and/or performing the task. Successful
      rehabilitation will reduce rehabilitative demand by reducing the level of
      difficulty associated with the goal or task and/or by reducing the value assigned
      by the patient to the goal or task (as a result of counseling or of learning
      alternative strategies). Within the framework of the model, changes in
      rehabilitative demand define effectiveness of intervention.

PMID- 8570161
TI  - Refractive index and osmolality of human tears.
AB  - Tear osmolality measurement, as a basic index of lacrimal physiology, is
      technically difficult. We investigated a simple, digital nanoliter technique of
      critical angle refractive index measurement. After initial comparison of the
      techniques with aqueous NaCl (0.5 to 1.4%), 3 successive tear samples were
      obtained from each of 40 normal, noncontact lens wearing subjects, aged 17 to 63
      years, for analysis by nanoliter osmometry and digital refractometry. In
      addition, tear lactoferrin concentration was estimated with the Lactoplate
      immunoassay. For the range of NaCl concentrations tested, osmolality and
      refractive index measurements were highly correlated with concentration, and with
      each other. For 0.9% NaClaq the mean value of osmolality was 292.0 mOsm/kg and
      refractive index was 1.33419. For human tears average values were found to be:
      for osmolality, 303.7 +/- 22.9 mOsm/kg; for refractive index, 1.33698 +/-
      0.00110; and for lactoferrin level, 1.64 +/- 0.47 mg/ml. No statistically
      significant correlation was obtained between either refractive index or
      lactoferrin level and osmolality, but refractive index and lactoferrin level were
      significantly correlated (r = 0.64, p < 0.001). The high correlation of
      refractometry and osmolality for aqueous NaCl indicates comparability of the
      techniques for this solution, but this does not apply to human tears. Unlike tear
      osmolality, tear refractive index is dependent to a greater extent upon
      composition, as is suggested by its correlation with lactoferrin level.
      Therefore, refractometry is not acceptable as a direct alternative to osmometry
      in the assessment of lacrimal function.

PMID- 8570163
TI  - Retinal correspondence under dynamic background.
AB  - We examined the binocular vision of 14 patients with esotropia under a dynamic
      background. The objective and subjective angles of the patients were measured
      using a phase difference haploscope under three conditions: no background (A), a
      static background produced by an image slide (B), and a dynamic background
      produced by 8-mm movies (C). The objective angle remained the same under
      different backgrounds. On the other hand, the subjective angle tended to become 0
      degree under condition C; that is, more harmonious abnormal retinal
      correspondence (HARC) was obtained under C. Therefore, it was concluded that HARC
      was more easily detected under the dynamic background than under the static or no
      background conditions.

PMID- 8570164
TI  - Design elements of professional ethics courses.
AB  - Optometrists face ethical dilemmas daily in the practice of their profession.
      Students training to become optometrists also face ethical dilemmas, some of
      which are unique in their role as students. The focus on ethical practice has
      been heightened by the increasing scope of optometric practice, the greater
      demand of society for professional accountability, the greater diversity of
      membership and viewpoints, the decrease in available dollars for health care
      delivery, and the conflicting roles of ophthalmology and opticianry with
      optometry. These factors have led to the addition or expansion of professional
      ethics courses in optometry programs. This paper examines the difficulties
      inherent in defining professional ethics and designing ethics courses. Curricular
      issues are examined, including course objectives, instructors, content,
      evaluation, timetabling, teaching strategies, student assessment, and resource
      implications. Much of the research in this area has been done in medical
      education. Although the content of ethical dilemmas encountered by medical
      students and physicians may not be applicable to optometry, the process by which
      they learn to approach the dilemmas is the same.

PMID- 8570165
TI  - On the short-term variability of measurements of intraocular pressure.
AB  - Measurement of intraocular pressure (IOP) (tonometry) is conducted routinely in
      the eye clinic for the diagnosis and management of primary open-angle glaucoma.
      Mean IOP may be influenced by a number of factors including ocular accommodation,
      spontaneous pulsations of IOP, and the effect of repeated applanation. A review
      of some of the factors that influence IOP should help us gain a perspective on
      the reliability of diurnal tonometry in the diagnosis of primary open-angle
      glaucoma.

PMID- 8570166
TI  - Pigmentation of the posterior lens capsule central to Wieger's ligament and the
      Scheie line: a possible indication of the pigment dispersion syndrome.
AB  - Observation of pigment deposition on the posterior lens central to Wieger's
      ligament and the position of the so-called Scheie line is reported as a clinical
      sign of the pigment dispersion syndrome (PDS). Although abnormal pigmentation of
      the posterior lens surface is well-known to occur as scattered deposition among
      the zonule insertions as well as in the shape of a line formed within the crevice
      just anterior to the junction between the posterior capsule and the anterior
      hyaloid face, pigmentation has not been well-known to occur more centrally,
      nearer the polar capsular region. Pigment in this location is a relatively
      unknown finding in PDS and may lead to suspicion and diagnosis of this disorder.

PMID- 8570167
TI  - Viral hepatitis: a review.
AB  - Viral hepatitis is neither a single disease condition nor is it caused by a
      single viral agent. Viral hepatitis can cause a wide spectrum of systemic
      manifestations. Here we concentrate on the five unrelated hepatitis viruses whose
      effect is limited almost entirely to the liver. More than 60,000 cases of viral
      hepatitis are reported to the U.S. Centers for Disease Control each year,
      although it is estimated that more than 300,000 cases actually occur. Some of the
      hepatitis viruses are present in all bodily fluids and, therefore, without
      adequate precautions, may be transmitted to either the health care provider or
      between patients in a clinical setting. The severity of an infection can be
      extremely variable among infections by the different virus types, as well as by a
      single virus type. Manifestations can range from the subclinical to the seriously
      acute to the chronic. In extreme cases, death can also result from infection, via
      such acute and chronic pathways as fulminant hepatitis, hepatocellular carcinoma,
      and cirrhosis of the liver. Because viral hepatitis is widely prevalent, can be
      transmissible in a clinical setting, and can have serious and long-lasting health
      consequences, all optometrists should be aware of some of the facts regarding
      viral hepatitis infections.

PMID- 8570168
TI  - Molecular cloning of a novel serine/threonine kinase, MRK, possibly involved in
      cardiac development.
AB  - We have isolated a novel member of putative serine/threonine kinase from a rat
      heart cDNA library using polymerase chain reaction methods. The novel kinase is
      transcribed as 2.6 kb mRNA encoding for a protein of 629 amino acids with the C
      terminal non-catalytic portion. Amino acids analysis revealed that the N-terminal
      catalytic domain is 87% identical to the male-germ cell associated kinase (MAK),
      a cdc2-related serine/threonine kinase found to promote meiosis during
      spermatogenesis. Therefore, we designated this novel kinase as the MAK-related
      kinase (MRK). MRK protein, with a molecular weight of 66 kD, was shown to
      phosphorylate itself and the exogenous substrates, histone H1 and myelin basic
      protein. In addition, phosphoamino acid analysis confirmed the serine/threonine
      specific protein kinase activity of MRK. Although MRK was ubiquitous in adult rat
      tissues, the expression of MRK protein in embryos was restricted primarily to
      embryonic myocardium during early organogenesis. This finding suggests that MRK
      may be a participant in cardiac development.

PMID- 8570169
TI  - Transcriptional activation plays a role in the induction of apoptosis by
      transiently transfected wild-type p53.
AB  - The p53 tumor suppressor gene has been implicated in the induction of apoptosis
      in several cell systems. We have recently reported than transiently-transfected
      wt p53 is capable of inducing apoptosis in certain transformed cell lines. We
      demonstrated by quantitative analysis using flow cytometry that apoptosis was
      restricted to the population expressing wt, but not mutant, p53. In the present
      study we use this model system to analyse the functional domain of p53 in the
      induction of apoptosis. Several constructs expressing mutations or deletions in
      the C-terminal oligomerization domain, the N-terminal transactivation domain or
      the central DNA-binding domain were introduced into HeLa cells, and the ability
      of the expressed proteins to induce apoptosis was evaluated. All the functional
      domains were found to be necessary for the induction of apoptosis. In addition,
      cycloheximide and actinomycin D inhibited wt p53-induced apoptosis. We therefore
      conclude that p53 acts in this cell system, at least in part, as a
      transcriptional activator in the induction of apoptosis.

PMID- 8570171
TI  - Oncogenic activity of Tiam1 and Rac1 in NIH3T3 cells.
AB  - We have recently identified the invasion-inducing Tiam1 gene by proviral
      insertional mutagenesis. The Tiam1 protein shares a Dbl homology (DH) domain with
      an increasing number of oncoproteins, some of which have been shown to function
      as GDP dissociation stimulators (GDS) for small GTPases of the Rho family. In
      vitro and in vivo analyses indicate that Tiam1 activates the Rho like GTPase
      Rac1. Here we have analysed the consequences of overexpression of several mutant
      Tiam1 proteins in NIH3T3 fibroblasts. Similar to other proteins containing a DH
      domain, N-terminal truncation of the Tiam1 protein activates its oncogenic
      potential, establishing Tiam1 as a proto-oncogene. In addition, we show the
      sequences N-terminal of the catalytic DH domain are required for morphological
      transformation accompanied by the formation of membrane ruffling, but not for the
      induction of an oncogenic phenotype. Overexpression of constitutively active Rac1
      (V12Rac1) in NIH3T3 cells produces a similar oncogenic phenotype, suggesting that
      the oncogenic effects of Tiam1 are a consequence of Rac activation.

PMID- 8570170
TI  - Ret receptor tyrosine kinase activates extracellular signal-regulated kinase 2 in
      SK-N-MC cells.
AB  - Ret is a receptor tyrosine kinase predominantly expressed in tissue derived from
      the neuroectoderm and is involved in multiple endocrine neoplasia type 2A and 2B,
      familiar medullary thyroid carcinoma, and Hirschsprung's disease. The ligand for
      the receptor is still unknown. Previously, using a human epidermal growth factor
      receptor - Ret chimaeric receptor (HERRet) stably transfected into fibroblasts,
      it was shown that Ret activation induces the activation of p21ras, but,
      surprisingly, activation of extracellular signal-regulated kinase 2 (ERK2) was
      not observed (Santoro et al. (1994) Mol. Cell. Biol., 14, 663). In this report we
      describe early signaling events induced by the activated HERRet fusion receptor
      in a cell line derived from neuroectodermal tissue, SK-N-MC. In these cells,
      activated HERRet induces tyrosine phosphorylation of Shc, complex formation of
      Shc with Grb2 and Sos and activation of p21ras. Importantly, also ERK2 is
      activated. This activation was strong and sustained for at least 2 h. Activation
      was abolished by the dominant negative p21rasasn17 mutant, showing that
      activation of ERK2 is mediated by p21ras. These results suggest that Ret can
      induce ERK2 activation in a p21ras dependent manner in cells derived from tissue
      where Ret is endogenously expressed.

PMID- 8570172
TI  - CD44 hyaluronate binding influences growth kinetics and tumorigenicity of human
      colon carcinomas.
AB  - CD44 is a cell surface receptor of hyaluronate that is implicated in the
      regulation of tumor growth and metastatic potential. Transformation of colon
      mucosa to carcinoma is associated with overexpression of several CD44 alternative
      splice variants. The functional roles of CD44 isoforms in colon carcinoma tumor
      progression remain unclear. CD44H expression is downregulated in colon carcinomas
      compared to paired normal mucosa. In the present study we demonstrate that
      reintroduction of CD44H back into colon carcinoma cells by stable transfection
      reduces their in vitro growth rate and tumorigenicity. Examination of several
      colon carcinoma cell lines and use of mutant CD44H reveal that this in vitro and
      in vivo growth reduction requires the ability of CD44H to bind hyaluronate. These
      observations indicate that the CD44H downregulation associated with
      transformation of mucosa to colon carcinoma may provide the carcinoma cells with
      a growth advantage. Furthermore, the reduction in tumor growth rate mediated by
      reintroduction of CD44H into colon carcinoma cells is dependent on its ability to
      bind hyaluronate.

PMID- 8570173
TI  - Overexpression of neu-related lipocalin (NRL) in neu-initiated but not ras or
      chemically initiated rat mammary carcinomas.
AB  - The activated neu (HER2/c-erbB-2) oncogene is extremely potent in inducing
      mammary cancer. For example, neu induces greater than 200 times as many tumors as
      the activated ras oncogene when directly introduced into in situ rat mammary
      epithelial cells using replication-defective retroviral vectors. In order to
      characterize mechanisms underlying this potency, we sought to identify uniquely
      overexpressed genes in neu-initiated tumors that were not overexpressed in tumors
      induced by weaker initiating agents, including activated ras and the chemical
      carcinogens dimethylbenz[a]anthracene and N-nitroso-N-methylurea. Several genes,
      including those encoding keratin K7 and the u haplotype of MHC class I RT1-A,
      were found to be overexpressed in neu-initiated carcinomas as well as in mammary
      carcinomas induced by other agents, when compared to their expression in normal
      mammary tissue. One gene, however, encoding a member of the lipocalin and calycin
      protein families, was 12-fold overexpressed in neu mammary tumors and was not
      overexpressed in ras or chemically induced carcinomas. This uniquely
      overexpressed gene was termed neu-related lipocalin (NRL). NRL protein was
      produced in a baculovirus system, purified and used to generate polyclonal
      antibodies. Western blot analysis indicate that neu-initiated mammary carcinomas
      express abundant NRL protein when compared to other mammary tumors.

PMID- 8570174
TI  - Cloning of the mouse homologue of the deleted in colorectal cancer gene (mDCC)
      and its expression in the developing mouse embryo.
AB  - Loss of DCC gene expression has now been demonstrated in a wide variety of
      metastatic cancers. Here we present the nucleotide sequence and predicted amino
      acid sequence of mouse DCC. Mouse and human DCC share 96% identity at the amino
      acid level. Analysis of DCC mRNA expression throughout the mid and late stages of
      gestation in the mouse, demonstrated that DCC mRNA is expressed at significantly
      higher levels in the developing mouse embryo than in any adult tissue. In
      addition, we show that an embryo-specific, alternatively spliced, form of DCC is
      expressed in day 9.5 through day 18.5 embryos. The expression of both
      alternatively spliced forms of DCC is developmentally regulated such that the
      embryonic form of DCC predominates in day 9.5 and 10.5 embryos. In the later
      stage embryos the expression of this alternatively spliced form of DCC is down
      regulated with respect to that of the adult form. Whole-mount in situ
      hybridization of day 11.5 mouse embryos revealed that DCC mRNA is expressed at
      high levels in the developing brain and the neural tube. However, no DCC mRNA
      could be detected in any other embryonic tissue at this stage of development.
      These observations suggest that during embryogenesis DCC may play a pivotal role
      in the development of the central nervous system.

PMID- 8570175
TI  - B-ATF: a novel human bZIP protein that associates with members of the AP-1
      transcription factor family.
AB  - A new member of the ATF/CREB family of transcription factors, called B-ATF, has
      been isolated from a cDNA library prepared from Epstein-Barr virus stimulated
      human B cells. B-ATF is a 125 amino acid nuclear protein possessing a basic
      leucine zipper domain that is most similar to the basic leucine zipper of ATF-3.
      Northern blot analysis of polyadenylated mRNA isolated from a variety of human
      tissues and established cell lines indicates that the 1.0 kilobase B-ATF mRNA is
      expressed differentially, with the strongest hybridization detected in lung and
      in Raji Burkitt's lymphoma. Efficient homodimerization of the B-ATF protein
      cannot be detected using the yeast two hybrid system or using in vitro binding
      assays with glutathione-s-transferase-B-ATF and maltose binding protein-B-ATF
      fusion proteins produced in E. coli. However, a yeast two hybrid library screen
      has identified the human oncoprotein JunB as a specific binding partner for B
      ATF. Glutathione-s-transferase-B-ATF heterodimerizes efficiently with in vitro
      translated JunB, c-Jun, and JunD, but only weakly associates with c-Fos. In
      addition, electrophoretic mobility shift assays demonstrate that a B-ATF/c-Jun
      protein complex can interact with DNA containing a consensus binding site for AP
      1, suggesting that B-ATF functions as a tissue-specific modulator of the AP-1
      transcription complex in human cells.

PMID- 8570176
TI  - Kir, a novel Ras-family G-protein, induces invasive pseudohyphal growth in
      Saccharomyces cerevisiae.
AB  - Kir belongs to a novel class of Ras-family G-proteins which includes Gem and Rad.
      These proteins are unique among Ras super-family G-proteins since their
      expression is under transcriptional regulation in mammalian cells. To gain
      insight into the function of Kir, we took advantage of the well-defined signal
      transduction pathways of yeast. When kir is expressed in Saccharomyces
      cerevisiae, the transformants form pseudohyphae and exhibit invasive properties
      characteristics of yeast cells undergoing a developmental transition induced by
      nitrogen starvation. Analysis of pseudohyphal signaling pathway mutants suggests
      that the Kir-induced pseudohyphae formation requires a MAP kinase cascade
      involving ste20, ste11, ste7 but not ste5 gene products. Furthermore, our results
      are consistent with the idea that Kir functions upstream of the STE20 kinase
      which plays a critical role in two distinct MAP kinase cascades.

PMID- 8570177
TI  - Expression of mouse c-myb during embryonic development.
AB  - Three members of the myb gene family, designated as A-myb, B-myb, and c-myb, have
      been described in many vertebrates. A large body of evidence indicates that the c
      myb gene is essential for the development of most hematopoietic lineages. By
      contrast, the functions of A-myb and B-myb are less well understood. To further
      explore the relationship between the different myb family members we have
      compared the expression of A-myb and c-myb during mouse embryogenesis by Northern
      blotting and by in situ hybridization. In accordance with the important role of c
      myb in the hematopoietic system, we detect high levels of c-myb expression in
      hematopoietic organs such as the fetal liver and the thymus. Surprisingly, we
      find that high levels of c-myb expression are not restricted to hematopoietic
      cells. We show that c-myb is strongly expressed in the neural retina and in
      epithelia of the respiratory tract. The side-by side analysis of c-myb and A-myb
      expression clearly shows that both genes are expressed in different, but
      overlapping sets of tissues. Our results suggest that the function of c-myb may
      not be restricted to hematopoietic cells.

PMID- 8570178
TI  - Most liver epithelial cell lines from C3B6F1 mice exhibit parentally-biased loss
      of heterozygosity at the Lci (Liver cell immortalization) locus on chromosome 4.
AB  - Liver epithelial cell lines established from F1 animals generated from
      hepatocarcinogen-sensitive C3H/HeJ and -resistant C57BL/6J mice were analysed for
      loss of heterozygosity at more than 60 simple sequence repeat marker loci
      distributed over all of the autosomal chromosomes. Nineteen of 20 clonal cell
      lines showed loss of heterozygosity at a chromosome 4 locus, designated Lci
      (Liver cell immortalization) and in most of the cases (18 of 19), alleles from
      the hepatocarcinogen-resistant parental strain, C57BL/6J, were lost. Detailed
      deletion mapping localized the putative suppressor gene for immortalization to
      within a 2 cM interval which includes a cluster of genes for gap junctional
      proteins. We also observed a loss of heterozygosity on chromosomes 7, 14, or 17
      in more than 50% of the cell lines.

PMID- 8570179
TI  - Analysis of the p16 gene, CDKN2, in 17 Australian melanoma kindreds.
AB  - CDKN2 has been implicated as a melanoma susceptibility gene in some kindreds with
      a family history of this disease. Mutation analysis of CDKN2 in 17 familial
      melanoma Australian kindreds revealed a paucity of exon mutations and none of the
      previously described disease-related mutations. One novel germline mutation was
      found in exon one, Arg24Pro, which segregates with melanoma in 1/17 kindreds. Two
      previously described polymorphisms, Ala148Thr and a base change at nucleotide 540
      were detected and one novel polymorphism in the untranslated region of exon 3
      (nucleotide 580) was also found. Together with other recent reports, these
      findings provide support for CDKN2 as a susceptibility locus for familial
      melanoma but suggest that other loci are involved in some hereditary melanoma
      kindreds.

PMID- 8570180
TI  - The three transforming regions of SV40 T antigen are required for immortalization
      of primary mouse embryo fibroblasts.
AB  - Simian virus 40 (SV40) is a small DNA tumor virus whose early region gene
      product, large T antigen, is sufficient to immortalize primary rodent cells and
      transform established rodent cell lines. Three functional domains of large T
      antigen are required for transformation of the rat embryo fibroblast REF 52 cell
      line: the extreme amino-terminal region, a domain which binds p105Rb family
      members, and the bipartite p53-binding region. Many studies have attempted to
      define the activities and regions of SV40 large T antigen required for
      immortalization of mouse embryo fibroblasts (MEFs). In most of these studies,
      investigators have used survival of T antigen-expressing primary MEF colonies at
      the time when controls MEFs undergo senescence as a measurement of
      'immortalization' and concluded that immortalization of MEFs is correlated with
      large T antigen's ability to sequester the human tumor suppressor gene product
      p53 and separable from its p105Rb-binding or N terminal functions. In order to
      more rigorously define the regions of SV40 large T antigen required for escape
      from senescence, individual T antigen-expressing primary MEF colonies were
      systematically subcultured for > 60 population doublings beyond the time of
      control MEF senescence under conditions known to limit the number of
      spontaneously immortalized cells. We found that although interaction of T antigen
      with p53 was sufficient to substantially extend the lifespan of MEFs, all three
      SV40 large T antigen domains required for REF 52 transformation were necessary to
      immortalize primary MEFs. These results indicate that p53 inactivation alone is
      insufficient to immortalize primary MEFs; rather, immortalization requires
      multiple activities of T antigen which are also required for efficient
      transformation.

PMID- 8570181
TI  - The microsatellite mutator phenotype of colon cancer cells is often recessive.
AB  - A new mutator mechanism for tumorigenesis, characterized by somatic genomic
      instability (SGI) at simple repeated sequences (SRS) or microsatellites,
      underlies hereditary nonpolyposis colorectal cancer (HNPCC) and some sporadic
      tumors of the colon and other types. To determine whether the microsatellite
      mutator phenotype (MMP) is dominant or recessive, we generate somatic cell
      hybrids between a tumor cell line without SGI at SRS (D98OR) and colon carcinoma
      cell lines with relative low (HCT-15) and high (LS174-T) SGI at SRS. The normal
      fidelity of replication of these unstable sequences was observed in each of these
      cell hybrids. Fusion of HCT-15/DLD-1 low instability cells, with LS174-T, HCT116
      and LoVo cell lines, all exhibiting relative high instability, also restored the
      replication fidelity of SRS in all of the hybrids. Hybrids between the high
      instability cell lines did not grow possibly because of senescence or apoptosis.
      These results indicate that, in the cell lines analysed, the characterized
      mutator phenotype of the mismatch repair system resulting in high SGI at SRS, and
      the uncharacterized mutator phenotype underlying low SGI at SRS, are both
      recessive. The results also suggest that different tumor cells of the MMP harbor
      distinct altered growth-related genes.

PMID- 8570182
TI  - Activation of p21WAF1/Cip1 expression by a temperature-sensitive mutant of human
      p53 does not lead to apoptosis.
AB  - The cyclin-dependent kinase inhibitor p21WAF1/Cip1 (p21) inhibits cellular
      proliferation and has been implicated in p53-dependent apoptosis. In this study,
      we examined the regulation of p21 in the K562 erythroleukemia cell line using a
      human temperature-sensitive mutant of p53, 143Ala. We showed that 143Ala at the
      permissive temperature (32 degrees C) activated the expression of p21. Stable
      cell lines expressing 143Ala or other p53 mutants were established. We then
      examined whether elevation of p21 promotes apoptosis and sensitized cells to
      radiation-induced apoptosis. Our results showed that p21 elevation did not
      promote or sensitize K562 cells to apoptosis.

PMID- 8570183
TI  - Structural requirements for the efficient regulation of the Src protein tyrosine
      kinase by Csk.
AB  - Protein tyrosine kinases of the Src family are negatively regulated by
      phosphorylation in the C-terminal tail of the molecule. A different protein
      tyrosine kinase, Csk, is largely responsible for this regulation. The
      phosphorylated tail of c-Src engages with the SH2 domain in a conformation that
      is associated with low kinase activity and which involves stabilization by the
      SH3 domain. Inducible expression of c-Src in fission yeast is lethal unless Csk
      is coexpressed. Using this assay we present evidence that Src regulation by C
      terminal phosphorylation does not require the myristylation signal or the unique
      domain at the N-terminus of the Src protein. Mutagenesis of the SH3 and SH2
      domains of Csk show that neither are necessary in yeast or in vitro for efficient
      regulation of Src. Mutation of Tyr416 of Src, a site of autophosphorylation
      common to most protein tyrosine kinases, abolished the ability of Src to arrest
      growth of phosphorylate endogenous proteins. Tyr416 had the same effect on a
      shorter form of Src consisting of the kinase domain only, indicating that the
      mutation affects a property intrinsic to the catalytic domain. The residual
      activity of full-length Src mutated at Tyr416 is efficiently repressed by Csk
      action, suggesting that regulation by C-terminal phosphorylation does not act by
      preventing phosphorylation at Tyr416.

PMID- 8570184
TI  - Molecular cloning of a cDNA encoding a phosphoprotein, Efs, which contains a Src
      homology 3 domain and associates with Fyn.
AB  - Src homology 2 and 3 (SH2 and SH3) domains mediate protein-protein interactions
      in intracellular signaling by protein-tyrosine kinases (PTKs). We have isolated
      cDNA clones from mouse embryo cDNA expression library that encode a new signaling
      protein which we call Efs (Embryonal Fyn-associated Substrate). The deduced amino
      acid sequence of 560 residues in length revealed one SH3 domain at its amino
      terminal region, two proline-rich motifs with the consensus sequences of binding
      to Src-family SH3s, and a cluster of YXXP motifs that are possibly tyrosine
      phosphorylated to serve as ligands binding to SH2 domains. Structure and
      alignment of these characteristics sequences are homologous to those of p130Cas,
      but Efs and p130Cas are different proteins. Expression of the Efs gene was higher
      in placenta, embryo and brain than in other adult tissues. Transfection of COS-7
      cells with a plasmid encoding an epitope-tagged Efs resulted in the expression of
      a 83 kDa protein. The epitope-tagged Efs was hyperphosphorylated when
      cotransfected with a vector expressing Fyn. In an in vitro kinase assay with the
      PCC4 cell lysate, Efs became phosphorylated on tyrosine residues and
      coprecipitated with p59fyn and p62yes; the result suggests that Efs is a
      physiological substrate of these PTKs.

PMID- 8570185
TI  - Translational enhancement of FGF-2 by eIF-4 factors, and alternate utilization of
      CUG and AUG codons for translation initiation.
AB  - The FGF-2 mRNA of most mammals contains a long and inhibitory 5' UTR in addition
      to at least two CUG codons upstream and in frame with the AUG start codon. These
      CUGs are used for translation initiation to generate several polypeptides. Cells
      overexpressing the translation initiation factor 4E produce and secrete large
      amounts of FGF-2, and particularly the largest, CUG1-initiated form.
      Overexpression of FGF-2 is due to a translational enhancement of its mRNA, as
      indicated by its association with large polyribosomes in contrast to control
      cells, where it partitions mostly in fractions lighter than 80 S or small
      polyribosomes. Breast carcinomas expressing elevated eIF-4E also exhibited the
      large FGF-2 isoforms, which could play an important role in tumor angiogenesis.
      Translation of in vitro transcribed rat FGF-2 in reticulocyte lysates resulted in
      synthesis of four polypeptides, of similar size to those observed in vivo.
      Addition of purified eIF-4F preferentially increased translation of CUG1- and AUG
      initiated isoforms. Since the different isoforms of FGF-2 may have different
      roles and intracellular distribution, the effects of the eIF-4 factors on FGF-2
      expression could be important for the control of cell proliferation and
      differentiation.

PMID- 8570186
TI  - A putative effector of Ral has homology to Rho/Rac GTPase activating proteins.
AB  - We report here the cloning of a gene encoding a novel Ral interacting protein
      (RIP1) from a cDNA expression library using radiolabeled Ral as probe. RIP1 binds
      to Ral in a GTP-dependent manner. The 4.1 kb transcript of the RIP1 gene is
      present in all tissues analysed and encodes for a protein product of 648
      residues. RIP1 shares sequence similarity with GAP proteins that are capable of
      activating the GTPase activity of members of the Rho/Rac family of GTPases. When
      tested, RIP1 could activate the GTPase activity of CDC42 and, to a lesser extent,
      Rac1 but not RhoA, Ras, or Ral. Activated Ral had no effect on the GTPase
      activating ability of RIP1, in vitro.

PMID- 8570187
TI  - Growth suppression of transformed human bronchial epithelial cells by all-trans
      retinoic acid occurs through specific retinoid receptors.
AB  - The retinoids are reported to chemoprevent second aerodigestive tract cancers in
      patients with prior lung or head and neck cancers. Since those retinoids already
      examined in clinical trials do not induce major clinical responses in lung
      cancers, it is hypothesized that the beneficial chemoprevention activity in lung
      neoplasias occurs within 'fields' of carcinogen-transformed epithelial cells. To
      begin to investigate this retinoid action during lung carcinogenesis, the BZR-T33
      ras transformed human bronchial epithelial cell line that grows in an anchorage
      independent manner was examined. This study reports, as compared to controls,
      that all-trans-retinoic acid (RA)-treatment suppresses BZR-T33 proliferation in
      monolayer cultures and in anchorage independent and cloning efficiency growth
      assays. RA induces RAR-gamma 2 > RAR gamma 1 in BZR-T33 cells but expression at
      the total cellular RNA level of RAR alpha and RXR alpha is not augmented by RA
      treatment. RAR beta mRNA expression is repressed before and after RA-treatment
      and is only detected using a reverse transcription polymerase chain reaction (RT
      PCR) assay. To determine directly which of these expressed retinoid receptors
      signals growth suppression, each receptor was individually transfected into BZR
      T33 cells using episomal vector in colony efficiency assays. RAR gamma over
      expression in the presence or absence of RA-treatment did not suppress BZR-T33
      growth more than controls. In contrast, over-expression of the other examined
      retinoid receptors inhibited BZR-T33 cellular cloning efficiency prior to RA
      treatment and in this decreasing order after RA-treatment: RAR alpha > RAR beta >
      RXR alpha. The findings reported here reveal that RA suppresses proliferation and
      cloning efficiency in this transformed human bronchial epithelial cell through
      specific retinoid receptors. Further work is needed to evaluate the role of RA or
      its nuclear receptors in inhibiting even earlier steps in lung carcinogenesis.

PMID- 8570188
TI  - Constitutively active MAP kinase kinase (MEK1) stimulates SAP kinase and c-Jun
      transcriptional activity in U937 human leukemic cells.
AB  - Treatment of U937 human leukemic cells with the phorbol ester PMA, activates both
      mitogen-activated protein kinase (MAPK) and stress-activated protein kinase
      (SAPK), stimulates c-Jun phosphorylation and transcriptional activity, and
      induces a macrophage-like differentiation of U937 cells. The involvement of the
      MAPK pathway in mediating both the early phosphorylation and transcriptional
      activation events and the chronic differentiation of U937 cells was examined
      utilizing constitutively active MAPK kinase (MEK1) mutants. Transient expression
      of an activated MEK1 construct in U937 cells was found to stimulate MAPK and SAPK
      activity, as well as enhancing AP1-, SRE- and c-Jun-mediated transcriptional
      activity. Transient transfection of MAPK phosphatase-1 (MKP-1), a protein
      phosphatase which preferentially dephosphorylates and inactivates MAPK, inhibited
      the functional effects of both PMA and the constitutively active MEK1 mutants. To
      determine whether specific activation of the MEK/MAPK pathway was sufficient to
      induce hematopoietic differentiation, U937 cell lines were established that
      conditionally expressed the activated MEK1 mutant under the control of the human
      IIa metallothionein promoter. The induction of constitutively active MEK1 protein
      expression resulted in an increase in MEK1 activity, c-Jun and AP-1
      transcriptional activity and an inhibition of U937 cell growth. However, this
      growth inhibition was not accompanied by U937 cell differentiation. These results
      suggest that a cross-talk mechanism exists between the MAPK and SAPK signal
      transduction pathways in U937 cells and that PMA-mediated SAPK activation may
      involve the MAPK pathway. Furthermore, selective activation of the MEK/MAPK
      pathway utilizing a constitutively active MEK1 mutant, while growth inhibitory,
      was not sufficient to induce the macrophage-like differentiation of U937 cells.

PMID- 8570189
TI  - Inhibition of colonic tumor cell growth by biliary glycoprotein.
AB  - Biliary glycoproteins (BGPs) are members of the carcinoembryonic antigen (CEA)
      family. These glycoproteins function in vitro as intercellular adhesion molecules
      and, in vitro as intercellular adhesion molecules and, in the mouse, serve as
      receptors for the mouse hepatitis viruses. In previous studies, BGP expression
      has been reported to be generally downregulated in colon and liver carcinomas of
      human, rat and mouse origins. We now demonstrate that introduction of murine Bgp1
      cDNA isoforms into a mouse colonic carcinoma cell line, negative for endogenous
      Bgpl expression, significantly alters the growth properties of these cells. Cells
      bearing two Bgp1 isoforms were growth-retarded and exhibited a reduced ability to
      form colonies in an in vitro transformation assay, when compared to parental or
      control neor cells. Furthermore, tumor formation was inhibited by 80% when cells
      bearing a full-length Bgp1 isoform were injected into BALB/c syngeneic mice,
      while cells expressing a Bgp1 isoform lacking most of the intracytoplasmic domain
      produced tumors as readily as the parental cells. There results indicate that a
      biliary glycoprotein isoform is involved in negative regulation of colonic tumor
      cell growth, by a process which requires its intracytoplasmic domain. The precise
      mechanisms causing Bgp-dependent tumor growth inhibition remain, however, to be
      defined.

PMID- 8570190
TI  - Urokinase-type plasminogen activator gene regulation by polyomavirus middle-T
      antigen.
AB  - Expression of polyomavirus middle-T antigen (middle-T) is involved in the
      formation of various tumors in vivo, e.g. hemangiomas and mammary gland tumors.
      Several genes have been shown to be activated in middle-T-expressing cells, but
      the underlying mechanisms have only been partially elucidated. Among the genes
      regulated by middle-T, the urokinase-type plasminogen activator (uPA) gene seems
      to be of primary importance for the development of the transformed phenotype. We
      have found that the uPA gene is highly expressed in eEnd2 cells derived from a
      hemangioma expressing middle-T. NIH3T3 cells show negligible levels of uPA mRNA
      but its expression was highly induced by infecting with a middle-T-expressing
      retrovirus. Middle-T did not affect uPA mRNA stability. Transient cotransfection
      experiments using a uPA-receptor gene construct and a middle-T expression vector
      showed that high uPA mRNA levels are due to increased uPA promoter activity.
      Analyses of various signaling molecules by transient cotransfection assays and in
      vitro kinase assays established that a signaling pathway involving c-Src, SOS,
      Ras, Raf-1 and ERK is activated by middle-T in NIH3T3 cells, resulting in the
      activation of the uPA gene promoter via PEA3/AP1 elements. In contrast, in eEND2
      cells uPA gene induction is only partially dependent on this pathway, suggesting
      the involvement of additional signaling molecules in endothelial cells.

PMID- 8570191
TI  - DCC expression is altered by multiple mechanisms in brain tumours.
AB  - The DCC (deleted in colorectal cancer) candidate tumor suppressor gene spans
      greater than 1350 kilobases at chromosomes 18q21.1 and encodes a transmembrane
      protein of unknown function. Although DCC is expressed in a number of adult
      tissues, its expression is highest in the brain and we have, therefore,
      undertaken studies to determine if DCC inactivation might contribute to tumors
      arising there. Decreased or absent DCC protein expression was noted in more than
      50% of the thirty brain tumors studied. Although specific mutations in the DCC
      gene were not identified, a variety of mechanisms appeared to contribute to the
      altered DCC expression, including allelic loss, aberrant splicing of transcripts
      and allele-specific loss of transcripts. In total, the data suggest that DCC
      inactivation may be important in brain tumor pathogenesis.

PMID- 8570192
TI  - Functional substitution identifies a cell survival promoting domain common to
      adenovirus E1B 19 kDa and Bcl-2 proteins.
AB  - The adenovirus E1B 19 kDa protein provides a cell survival function during
      adenovirus infection and facilitates efficient virus replication by preventing
      premature cell death. These functions resemble those performed by the protein
      coded by the proto-oncogene Bcl-1. The Bcl-1 protein, which provides a survival
      function in cells exposed to a number of cell death-inducing stimuli, can
      substitute for the 19 kDa protein during adenovirus infection. Although these two
      survival- promoting proteins are not overtly related by primary amino acid
      sequence, they appear to share short homologous sequences. In order to determine
      if these sequence motifs constitute common functional domains, we carried out
      domain exchanges between the 19 kDa and Bcl-2 proteins. Our results indicate that
      a seven amino acid region of the Bcl-2 protein (108-YRRDFAE-114) can efficiently
      substitute for the corresponding 19 kDa domain (47-YKWEFEE-53). Mutagenizing this
      domain in Bcl-2 abolishes the survival promoting activity of Bcl-2. Substitution
      of the kDa sequences into Bcl-2 restores the survival promoting activity, albeit
      at reduced levels. Our results suggest that this domain (designated NH1) may
      constitute a common functional domain for the 19 kDa protein and survival
      promoting members of the Bcl-2 family of proteins.

PMID- 8570193
TI  - c-Myc induces apoptosis in epithelial cells by both p53-dependent and p53
      independent mechanisms.
AB  - We tested the hypothesis that wild-type p53 activity is required for c-Myc
      dependent apoptosis in epithelial cells. Primary baby rat kidney epithelial cell
      lines were generated by immortalization through the concerted action of c-Myc and
      a temperature-sensitive (ts) dominant inhibitory mutant allele of p53 (BRK
      myc/p53ts cells). When shifted to the permissive temperature for wild-type p53
      activity, the BRK myc/p53ts cells underwent growth arrest and apoptosis. However,
      apoptosis also could be induced by serum deprivation at the nonpermissive
      temperature, when p53 was in the mutant state. Bcl-2 suppressed both modes of
      cell death. Apoptosis induced by wild-type p53 but not by serum deprivation was
      accompanied by G1 cell cycle arrest and increased expression of the Bcl-2
      antagonist Bax. We concluded that c-Myc could induce apoptosis in epithelial
      cells by at least two mechanisms that could be distinguished by their p53
      requirement. Our results support the possibility that c-Myc-dependent cell death
      might be exploited for therapeutic ends during carcinoma development, without
      regard to p53 status of the target cell.

PMID- 8570194
TI  - RET activation by germline MEN2A and MEN2B mutations.
AB  - The RET proto-oncogene encodes a receptor tyrosine kinase (TK). It has been shown
      that distinct germline mutations in the RET proto-oncogene are associated with
      the dominantly inherited cancer syndromes multiple endocrine neoplasia type 2A
      and 2B (MEN 2A and MEN 2B) and familial medullary thyroid carcinoma (FMTC) as
      well as Hirschsprung disease (HSCR), a congenital disorder characterised by
      absent enteric innervation. In this study, we have transfected NIH3T3 and PC12
      phaeochromocytoma cells with MEN2A (Cys634-> Arg) and MEN2B (Met918-> Thr) RET
      constructs. Both caused transformation of the NIH3T3 cells and differentiation of
      PC12 cells. The Ret (MEN2A) and Ret (MEN2B) proteins were constitutively
      phosphorylated on tyrosine, and their in vitro kinase activity was significantly
      higher than that of the wild type protein. The MTC cell line TT carries a CYs634
      > Trp MEN2A mutation, and we have shown by immunoelectronmicroscopy that Ret is
      clustered on the cell surface in a manner reminiscent of ligand-induced
      aggregation of cell surface receptors. RET is activated, as RET/PTC oncogene, by
      somatic rearrangements which link the TK domain to a constitutive dimerization
      interface in papillary thyroid carcinomas. We have compared the biological and
      biochemical activity of the TK domains of the wild type and MEN 2B Ret in the
      context of the RET/PTC. The results show that the MEN 2B mutation significantly
      increases the TK domain enzymatic activity suggesting that dimerization may be
      still necessary for MEN 2B Ret to express its full activity.

PMID- 8570195
TI  - Genomic organization and alternatively processed forms of Cek5, a receptor
      protein-tyrosine kinase of the Eph subfamily.
AB  - The genomic organization of Cek5, a receptor tyrosine kinase of the Eph
      subfamily, was elucidated utilizing a strategy involving PCR amplification of
      Cek5 genomic DNA. Cek5 is the first Eph-related kinase for which the exon-intron
      structure of the entire coding region has been determined. The Cek5 gene spans
      over 35 kb and comprises at least 16 exons. The exon-intron structure of Cek5 can
      be correlated with the proposed domain structure of the Eph subfamily, with the
      exception of an Ig motif in the extracellular domain. Intron positions in the
      Cek5 gene coincide with the locations of the deletions, substitutions, or
      insertions that have been described in a number of Eph-related kinases. This
      suggests that alternative processing plays a major role in generating the
      structural variability observed in the Eph subfamily. Consistent with this
      hypothesis, analysis of the Cek5 gene indicate that: (i) a variant form of Cek5
      containing an insertion in the juxtamembrane region (Cek5 +) arises through the
      use of alternative 5' splice sites, and (ii) a soluble form of Cek5 comprising
      only the extracellular domain (Cek5s) may exists, which originates by alternative
      polyadenylation. RT-PCR analysis and RNase protection assays revealed the
      expression of both Cek5 + and Cek5s at various stages of chicken development.

PMID- 8570196
TI  - Blocking c-Myc and Max expression inhibits proliferation and induces
      differentiation of normal and leukemic myeloid cells.
AB  - Given the central role c-Myc plays in growth control, differentiation and
      apoptosis, understanding how c-Myc functions will increase our understanding
      about normal cell development, and how alterations in these processes can lead to
      malignancy. C-Myc is a negative regulator of terminal myeloid differentiation;
      therefore, it was of interest to determine what effect blocking c-Myc expression
      would have on proliferation and differentiation. In this work we showed that
      blocking expression of either c-Myc or Max, its molecular partner, in
      myeloblastic leukemia M1 cells activated the differentiation program in the
      absence of an exogenous source of differentiation inducer; the cells assumed an
      intermediate stage myeloid morphology. Moreover, when both c-Myc and Max
      expression was concommitantly blocked, many of the cells underwent terminal
      differentiation. Finally, extending these studies to myeloblast enriched normal
      bone marrow (BM) cell has shown that blocking expression of either c-Myc or Max
      accelerated GM-CSF-induced differentiation along both the granulocytic and
      monocytic lineages. Thus, it can be concluded that blocking either c-Myc or Max
      expression in myeloid cells at specific stages of development activates and
      accelerates the terminal differentiation program.

PMID- 8570197
TI  - MDM2 transformation in the absence of p53 and abrogation of the p107 G1 cell
      cycle arrest.
AB  - The p53 tumour-suppressor guards the genome in response to genotoxic stress by
      transcriptional regulation of genes involved in cell-cycle control, DNA
      replication, repair and apoptosis such as p21, GADD45, bax and mdm2 (Cox and
      Lane, 1995). Mdm2 is classically considered to be an inhibitor of p53, that forms
      an auto-regulatory loop (Momand et al., 1992; Oliner et al., 1993; Wu et al.,
      1993; Chen et al., 1994; Chen and Levine, 1995). It immortalises cells containing
      wild type p53 and transforms them together with Ras (Finlay, 1993). We show that,
      in the absence of p53, mdm2 confers a growth advantage to cells (i.e.
      "transforms" them) and can overcome a G1 cell-cycl arrest induced by p107, a
      member of the pRb tumour-suppressor family (Adams and Kaelin, 1995). The minimum
      "transforming" and p107 inhibiting region of Mdm2 corresponds to its p53 binding
      domain. p53 inhibits transformation by Mdm2, apparently without requiring
      transcription. p53 can be considered to be a suppressor of Mdm2, a positive
      effector of the cell cycle. Mdm2 over-expression in tumours is reminiscent of p53
      mutations with gain of function, in that Mdm2 both transforms cells and inhibits
      p53 activity.

PMID- 8570198
TI  - CDKN2 (MTS1) tumor suppressor gene mutations in human tumor cell lines.

PMID- 8570199
TI  - A single ets-related transcription factor, E1AF, confers invasive phenotype on
      human cancer cells.
AB  - Invasion of cancer cells is the first step of metastasis. The invasive activity
      is thought to be dependent on the production of matrix metalloproteinases (MMPs).
      The transcription regulatory regions of MMP genes often contain binding sites for
      Ets and AP-1 transcription factors and they mediate oncogene- and growth factor
      induced transcription of the genes. We recently isolated the cDNA encoding human
      E1AF, a new member of ets oncogene family. E1AF highly stimulated transcription
      from three different subclasses of MMP genes in transient expression assays. Here
      we show that transfection of the non-invasive human breast cancer cell line MCF-7
      with the E1AF expression plasmid results in induction of invasive and motile
      activities, accompanied by an increase of 92 kD type IV collagenase (MMP-9) gene
      expression. Tumors derived from the E1AF transfectant were highly invasive and
      produced MMP-9. Expression of E1AF and MMP-9 genes was elevated in several
      invasive tumor cell lines. These results provide evidence for an important role
      of ets-related E1AF in tumor cell invasion.

PMID- 8570200
TI  - Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene
      superfamily, in a human myxoid chondrosarcoma.
AB  - The specific chromosomal translocation t(9;22)(q22-31;q11-12) has been observed
      in the myxoid variant of human chondrosarcoma. In agreement with this observation
      we report that the EWS gene located at chromosome band 22q12 becomes fused to
      CHN, a member of the steroid/thyroid receptor gene superfamily located at 9q22
      31, in a skeletal myxoid chondrosarcoma. CHN appears to be the human homologue of
      the rat gene NOR1, which was recently identified as a sequence overexpressed in
      rat brain cells undergoing apoptosis. Our results also indicate that the
      chimaeric EWS-CHN gene encodes a EWS-CHN fusion protein in which the C-terminal
      RNA-binding domain of EWS is replaced by the entire CHN protein, comprising a
      long N-terminal domain, a central DNA binding domain and a C-terminal ligand
      binding/dimerisation domain.

PMID- 8570201
TI  - Regulation of radiation-induced apoptosis in oncogene-transfected fibroblasts:
      influence of H-ras on the G2 delay.
AB  - Primary fibroblasts, after serum withdrawal or after irradiation, do not undergo
      apoptosis. Myc-transfected fibroblasts, in contrast, undergo apoptosis upon serum
      withdrawal and after irradiation. We have studied the relationship of apoptosis
      induction to effects on the G2 phase cell cycle in a series of rat embryo cells
      transformed by rasH plus myc or immortalized by myc alone. In this system, while
      the presence of rasH had little effect on the extent of apoptosis induction by
      serum withdrawal, rasH greatly suppressed the apoptotic response of myc
      transfected cells to X-rays. The cells into which rasH had been introduced showed
      a profound G2 arrest associated with suppression of cyclin B1 mRNA expression. In
      contrast, cells with myc alone had a minimal G2 delay after irradiation and no
      suppression of cyclin B1 mRNA expression. We hypothesize that rasH, by
      influencing the G2 response of cells to X-rays, exerts an anti-apoptotic effect.
      In support of this hypothesis; we found that treatment of cells with caffeine, an
      agent that relieves the G2 delay after irradiation resulted in increased
      apoptosis in the irradiated cells, but not in control cells.

PMID- 8570202
TI  - A gene on 6q 14-21 restores senescence to immortal ovarian tumor cells.
AB  - We have identified a gene on 6q14-21 which restores senescence to immortal
      ovarian tumor cells. Single gpt tagged human chromosomes, present in mouse/human
      monochromosomal hybrids, were introduced into immortal human and rat ovarian
      tumor cells via microcell fusion. Analysis of chromosome transfer clones for cell
      morphology and growth properties revealed that chromosome 6 or 6q restored
      senescence to both human and rat ovarian tumor cells while chromosomes 10 or 14
      did not affect the proliferative potential of these cells. Reversion to immortal
      growth concordant with loss of the donor chromosome confirmed the presence of a
      senescence gene on 6q. During continuous maintenance of microcell hybrids in MX
      medium, rare immortal revertant clones grew out of the human and rat senescent
      cell populations. Analysis of independent revertant clones of rat cells, for
      chromosome 6 markers, revealed a common deletion of chromosomal region 6q14-21 in
      all revertants. Restoration of senescence following introduction of a gpt tagged
      chromosome segment 6q13-21 into human and rat ovarian tumor cells confirmed the
      location of a senescence gene in this region. In contrast, introduction of a
      chromosome 6 lacking the region 6q14-21 did not impart senescence in these cells.
      Based on these results we assigned the senescence gene (SEN 6A) to region 6q14
      21.

PMID- 8570203
TI  - Association of CD45 with Lck and components of the Ras signalling pathway in
      pervanadate-treated mouse T-cell lines.
AB  - Pervanadate treatment of a mouse T-cell hybridoma cell line overexpressing an
      activated form of p56lck was shown to result in tyrosine phosphorylation of CD45.
      Immunoprecipitates prepared under mild lysis conditions using antibodies against
      CD45 contained a number of other proteins, including p56lck, that were not
      evident in the absence of pervanadate treatment or in T cells lacking activated
      Lck, implying that under these conditions, CD45 is present within complexes
      containing Lck and other proteins. Analyses involving deletion mutants of p56lck
      indicated that interactions with CD45 did not absolutely require the SH2 and SH3
      regions of Lck. Three proteins of the Ras signalling pathway were also shown to
      associated with CD45: the GTPase-activating protein for Ras (rasGAP), the
      signalling protein Grb2, and, possibly via complex formation with Grb2, the
      guanine nucleotide exchange factor mammalian son of sevenless (mSOS). In
      addition, CD45 was also found in immunoprecipitates prepared from these cells
      using an antiserum which recognizes Vav. It is possible that rasGAP, Grb2 and Vav
      bind to phosphotyrosine residues on CD45 via SH2 domains, and such interactions
      may be specific as other SH2-containing proteins, including phospholipase C alpha
      (PLC gamma), the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase). She
      and Syp/PTP1D were not detectably associated with CD45 under the same conditions.
      These data suggested that in addition to its role as a protein tyrosine
      phosphatase, CD45 may participate in T-cell activation by serving as a membrane
      docking site for components of the Ras signalling pathway.

PMID- 8570205
TI  - c-Myc overexpression associated DHFR gene amplification in hamster, rat, mouse
      and human cell lines.
AB  - We have analysed relative DHFR gene copy numbers in nine cell lines of various
      cell type and species origins. The cells studied expressed either low, low and
      inducible or constitutively elevated levels of c-Myc protein. DHFR gene
      amplification was observed only when c-Myc protein levels were upregulated. The
      amplification of the DHFR gene was transient in inducible cell lines. Cell lines
      exhibiting constitutively deregulated c-Myc protein levels, however, showed both
      DHFR gene amplification and ongoing rearrangements of the DHFR locus. In
      contrast, the relative gene copy numbers of ribonucleotide reductase R1 subunit,
      ornithine decarboxylase, syndecan 2, glyceraldehyde-3-phosphate-dehydrogenase,
      and cyclin C remained unaffected irrespective of c-Myc protein levels, suggesting
      a locus-specific genomic instability of the DHFR gene in cells with deregulated c
      Myc protein levels. Overall, the results of the present study support the notion
      that DHFR gene amplification as a consequence of c-Myc deregulation may occur in
      a variety of cell lines irrespective of their cell type and species origins.

PMID- 8570204
TI  - The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia
      produces a novel fusion gene, NPM-MLF1.
AB  - A t(3;5)(q25.1;q34) chromosomal translocation associated with myelodysplastic
      syndrome and acute myeloid leukemia (AML) was found to rearrange part of the
      nucleophosmin (NPM) gene on chromosome 5 with sequences from a novel gene on
      chromosome 3. Chimeric transcripts expressed by these cells contain 5' NPM coding
      sequences fused in-frame to those of the new gene, which we named
      myelodysplasia/myeloid leukemia factor 1 (MLF1). RNA-based polymerase chain
      reaction analysis revealed identical NPM-MLF1 mRNA fusions in each of the three
      t(3;5)-positive cases of AML examined. The predicted MLF1 amino acid sequence
      lacked homology to previously characterized proteins and did not contain known
      functional motifs. Normal MLF1 transcripts were expressed in a variety of
      tissues, most abundantly in testis, ovary, skeletal muscle, heart, kidney and
      colon. Anti-MLF1 antibodies detected the wild-type 31 kDa protein in K562 and HEL
      erythroleukemia cell lines, but not in HL-60, U937 or KG-1 myeloid leukemia
      lines. By contrast, t(3;5)-positive leukemia cells expressed a 54 kDa NPM-MLF1
      protein, but not normal MLF1. Immunostaining experiments indicated that MLF1 is
      normally located in the cytoplasm, whereas NPM-MLF1 is targeted to the nucleus,
      with highest levels in the nucleolus. The nuclear/nucleolar localization of NPM
      MLF1 mirrors that of NPM, indicating that NPM trafficking signals direct MLF1 to
      an inappropriate cellular compartment in myeloid leukemia cells.

PMID- 8570206
TI  - HIV-tat protein is a heparin-binding angiogenic growth factor.
AB  - Transgenic animal studies have linked the expression of the HIV-1 tat gene to the
      appearance of Kaposi's sarcoma (KS)-like lesions. We have recently shown that
      recombinant tat is angiogenic in vivo, and that tat angiogenic response is
      enhanced by heparin. Also in the rabbit cornea model, recombinant HIV-1 tat alone
      is poorly angiogenic, but gives a good response when combined with heparin. Like
      many angiogenic growth factors, tat has a basic domain similar to that of several
      heparin binding angiogenic factors, including FGF, VEGF and HGF, suggesting that
      this region is important in endothelial cell activation. We show that tat binds
      heparin sepharose with a high affinity, similar to bFGF. Binding of tat to the
      cell surface is also modulated by heparin. Biological activities of tat, such as
      induction of endothelial cell growth, migration and invasion in vitro are all
      enhanced by low concentrations and inhibited by high concentrations of heparin,
      as has been shown for other heparin-binding angiogenic factors. Heparan sulfate
      is also effective, whereas the unsulfated polysaccharide K5 does not enhance tat
      activity. Furthermore, a peptide encompassing the tat basic domain is able to
      induce growth and migration of endothelial cells, while an adjacent peptide is
      not. Our data indicate that the tat basic domain plays a key role in its vascular
      cell activation properties, and strongly suggest that extracellular HIV-tat is
      essentially a 'new' heparin-binding angiogenic factor.

PMID- 8570207
TI  - Expression and maturation of the cellular sea receptor, a member of the
      hepatocyte growth factor (HGF) receptor family of protein tyrosine kinases.
AB  - The c-sea proto-oncogene is a member of the Met/hepatocyte growth factor/scatter
      factor family of receptor protein tyrosine kinases. A distinguishing feature of
      this family, whose other member is the Ron/Stk receptor, is a novel heterodimeric
      structure. We have previously described cDNA clones encoding the avian Sea
      receptor. In this report we show that a full length c-sea cDNA directed the
      synthesis of a single 155 kDa polypeptide chain in vitro, while in vivo two
      polypeptides of 160 and 180 kDa were observed. We analysed the structure of the
      Sea receptor using a soluble chimeric protein consisting of the Sea extracellular
      domain linked to the hinge and constant regions of human IgG gamma 1. These
      studies indicated that the receptor undergoes proteolytic processing in the
      extracellular domain yielding an approximate 35 kDa alpha and a 160 kDa beta
      chain, and thus the Sea receptor appears to display a structure similar to that
      of the Met and Ron proteins. An examination of embryonic avian tissues using Sea
      extracellular domain-specific monoclonal antibodies revealed low levels of Sea
      receptor in a variety of tissues including kidney, intestine, liver, stomach,
      white blood cells and allantochorion. Elevated levels of expression were observed
      upon transformation of chicken embyro cells by the Src oncoprotein.

PMID- 8570208
TI  - Withdrawal of differentiation inhibitory activity/leukemia inhibitory factor up
      regulates D-type cyclins and cyclin-dependent kinase inhibitors in mouse
      embryonic stem cells.
AB  - The expression of E and D-type cyclins, Cyclin-Dependent Kinase (CDK) 2 and 4, as
      well as CDK inhibitors p21Cip1 and p27Kip1 were examined during in vitro
      differentiation of mouse embryonic stem (ES) cells. ES cells cultured in presence
      of Differentiation Inhibitory Activity/Leukemia Inhibitory Factor (DIA/LIF)
      express very low levels of cyclin E/CDK2 complexes, p21Cip1 and p27Kip1 CDK
      inhibitors, while cyclin D/CDK4-associated kinase activity is undetectable.
      Withdrawal of DIA/LIF, which induces differentiation, results in the progressive
      up-regulation of all. Up-regulation of D cyclins occurs through an increase in
      the steady-state levels of mRNA, concomitantly with the activation of Brachyury
      and Goosecoid, two early markers of mesoderm differentiation. Similarly, cells
      from the epiblast of the early postimplantation mouse embryo do not express any
      cyclin D/CDK4 complexes. These are progressively upregulated at gastrulation and
      early organogenesis. DIA/LIF-stimulated ES cells are not growth-arrested by
      overexpression of p16Ink4a, a specific inhibitor of CDK4 and CDK6. We propose
      that the G1/S transition may be regulated by a minimal mechanism in mouse
      embryonic stem cells. Induction of differentiation triggers the establishment of
      a more sophisticated mechanism involving both cyclin D/CDK4- and CDK inhibitor
      associated control of G1-phase progression.

PMID- 8570209
TI  - Reduced and altered DNA-binding and transcriptional properties of the PLZF
      retinoic acid receptor-alpha chimera generated in t(11;17)-associated acute
      promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) associated with chromosomal rearrangement
      t(11;17) is a distinct syndrome which, unlike typical t(15;17) APL, fails to
      respond to all-trans retinoic acid (ATRA) therapy. In t(11;17) the PLZF gene,
      encoding a Kruppel-like zinc finger protein, is fused to the retinoic acid
      receptor-alpha (RAR alpha) gene, yielding two classes of chimeric proteins. PLZF
      protein was found in the nucleus in a punctate speckled pattern that differed
      from the nuclear body expression pattern of the PML protein affected in t(15;17)
      APL. The reciprocal PLZF-RAR alpha and RAR alpha-PLZF fusion proteins were
      localized to the nucleus both in the presence and absence of ATRA. PLZF-RAR
      alpha, in combination with the retinoid X receptor (RXR) bound to a retinoic acid
      responsive element (RARE) less efficiently than RAR alpha and formed multimeric
      DNA-protein complexes. PLZF-RAR alpha stimulated ATRA-dependent transcription of
      RARE-containing reporter genes with diminished activity compared to wild-type RAR
      alpha. In addition, PLZF-RAR alpha antagonized the function of coexpressed wild
      type RAR alpha, an effect relieved by over-expression of RXR. Leukemogenesis in
      t(11;17) APL may be related to interference with ATRA-mediated differentiation
      due to sequestration of RXR by the PLZF-RAR alpha chimera. However, disruption of
      the function of the myeloid-specific PLZF protein may also play an important
      role.

PMID- 8570210
TI  - The Gag-Myb-Ets fusion oncogene alters the apoptotic response and growth factor
      dependence of interleukin-3 dependent murine cells.
AB  - Expression of the avian E26-derived Gag-Myb-Ets fusion oncogene in interleukin
      3(IL3)-dependent murine hematopoietic cell lines results in a pattern of cell
      line dependent changes in growth factor-induced proliferation and apoptosis. A
      drug-selectable retrovirus expressing p135Gag-Myb-Ets induced an
      erythropoietin(Epo)-responsive phenotype in the cell lines FDC-P2, BaF3 and
      32Dc123. Gag-Myb-Ets expression alone did not increase expression of GATA-1 or
      the Epo receptor(EpoR) in the presence of IL3, and infected cell lines express
      increased GATA-1 and EpoR only when IL3 was replaced by Epo in the culture media.
      Indicative of Epo-induced erythroid differentiation, these cells also began to
      express beta-globin after 3-5 days growth in Epo. Unlike control cells, infected
      FDC-P2 cells failed to undergo programmed cell death (apoptosis) when transferred
      from IL3- to Epo-containing media, although a fraction of the cells failed to
      proliferate following the media shift. Three other IL3-dependent cell lines
      showed no changes in growth behavior when induced to express the fusion oncogene.
      Our data shows that Gag-Myb-Ets can have different affects on growth factor
      pathways depending on the cell background, suggesting a model in which the
      p135gag-myb-ets fusion oncogene promotes these different responses through its
      affect on apoptosis.

PMID- 8570211
TI  - Betacellulin activates the epidermal growth factor receptor and erbB-4, and
      induces cellular response patterns distinct from those stimulated by epidermal
      growth factor or neuregulin-beta.
AB  - Betacellulin is a member of the epidermal growth factor (EGF) family. These
      soluble proteins are ligands for one or more of the four receptor tyrosine
      kinases encoded by the erbB gene family (erbB-1/epidermal growth factor receptor
      (EGFR), neu/erbB-2/HER2, erbB-3/HER3 and erbB-4/HER4). While evidence suggests
      that betacellulin is a ligand for the EGFR, the ability of betacellulin to
      regulate other erbB family receptors has not been analysed. Previously we
      engineered derivatives of the mouse Ba/F3 hematopoietic cell line to ectopically
      express erbB family receptors, singly and in pairwise combinations. We have
      stimulated this panel of cell lines with betacellulin and two other EGF family
      members, EGF itself and neuregulin-beta (NRG-beta). In the cell lines expressing
      a single erbB family receptor, betacellulin not only stimulated EGFR tyrosine
      phosphorylation, but it activated erbB-4 as well. Furthermore, in the double
      recombinant Ba/F3 derivatives, betacellulin stimulated a complex pattern of
      receptor phosphorylation distinct from the patterns activated by NRG-beta and
      EGF. Moreover, betacellulin stimulated a complex pattern of interleukin-3
      independence in the Ba/F3 derivatives distinct from those activated by NRG-beta
      and EGF. These data identify a novel receptor for betacellulin and establish that
      different EGF family ligands activate distinct patterns of receptor
      phosphorylation and coupling to cellular signaling pathways.

PMID- 8570212
TI  - B-Myb prevents growth arrest associated with terminal differentiation of
      monocytic cells.
AB  - B-Myb is a transcriptional regulator of gene expression and is highly homologous
      to c-Myb in its N-terminal DNA binding domain. However, unlike c-myb, whose
      expression is restricted largely to immature hematopoietic cells, B-myb mRNA has
      been found to be expressed in all proliferating mammalian cell lines and is
      clearly regulated in a cell cycle dependent manner. That c-Myb and B-Myb proteins
      perform different roles in proliferation and/or differentiation is suggested by
      the redundancy of their expression. It was previously shown that degenerated c
      Myb expression can inhibit IL-6 induced terminal differentiation of the leukemia
      cell line M1. We found that, unlike the downregulation of c-Myb protein which is
      an early response of progenitor M1 cells to IL-6 treatment, the downregulation of
      B-Myb occurs late, just prior to terminal differentiation and growth arrest. It
      was, therefore, of interest to examine the role of the murine B-Myb protein in
      the proliferation and differentiation of the M1 cells and to compare these
      effects to those of c-Myb in the same system. Clones ectopically producing B-Myb,
      like those ectopically expressing c-Myb, proliferated in the presence of the
      differentiation-inducing agent and did not undergo the programmed cell death
      which normally follows terminal macrophage differentiation. In addition, the cell
      cycle distribution of M1/B-Myb cells was comparable to untreated cells. Although
      M1/B-Myb and M1/c-Myb clones treated with IL-6 appeared quite immature,
      differentiation markers were demonstrated to be maintained at near normal levels
      (e.g. MyD88, Mac-2), or be partially reduced in expression (C3, Fc and Mac-1
      receptors) suggesting that the cells had undergone commitment to maturation, but
      were unable to terminally differentiate.

PMID- 8570213
TI  - Frequent allelic loss at chromosome arm 3p is distinct from genetic alterations
      of the Von-Hippel Lindau tumor suppressor gene in head and neck cancer.
AB  - Previous molecular genetic studies revealed that allelic loss of chromosome arm
      3p is a frequent event in upper aerodigestive tract squamous cell carcinoma (UADT
      SCC). Recently, the Von-Hippel Lindau (VHL) tumor suppressor gene was identified
      at chromosome band 3p25-26. To determine if the VHL locus is altered in these
      tumors, a paired series of 26 tumors and blood from patients with UADT SCC that
      were previously shown to exhibit allelic loss of 3p were tested for LOH
      surrounding the VHL locus using four different polymorphic markers. All of the
      samples (100%) exhibited LOH for at least 1 marker. However, no LOH was detected
      using a polymorphism within exon 1 of the VHL gene which was informative for 18
      of the 26 cases. Furthermore, mutations of the VHL gene could not be identified
      by single-strand conformation polymorphism, dideoxyfingerprint or direct DNA
      sequence analysis. In addition, the VHL gene was not inactivated by
      hypermethylation in any of the 26 tumor samples studied. These findings
      demonstrate that allelic loss of chromosome arm 3p in UADT SCC involves regions
      surrounding the VHL locus but does not include the VHL gene. The VHL gene,
      therefore, does not appear to be involved in the pathogenesis of UADT SCC.

PMID- 8570214
TI  - The role of Grb2 in the growth and transformation of mouse embryo cells.
AB  - An overexpressed insulin-like growth factor I receptor (IGF-IR) allows cells to
      grow in IGF-I only and to form colonies in soft agar. Conversely, cells with a
      targeted disruption of the IGF-IR genes, R- cells, are refractory to
      transformation by several oncoproteins and growth factor receptors, that readily
      transform their wild type counterparts, W cells. Grb2 is an SH2-SH3 domains
      protein that links tyrosine kinase receptors to ras signalling. In order to
      determine its role in mitogenesis and transformation, we have transfected a
      plasmid expressing Grb2 into R- and W cells, and their derivatives already
      expressing the SV40 large T antigen. In addition, we have used loss-of-function
      mutants of Grb2 to inquire whether they would act as dominant negatives. Our
      results show that: (1) an overexpressed Grb2 cannot replace the IGF-IR in IGF-I
      mediated mitogenesis; (2) Grb2 also fails to transform either W or R- cells; (3)
      Grb2 and SV40 T antigen, singly transfected, cannot transform R- cells, but can
      do so when combined; and (4) SH3 domain mutants of Grb2 act as dominant
      negatives, causing reversion of the transformed phenotype. We conclude that Grb2
      is necessary but not sufficient for transformation.

PMID- 8570215
TI  - Expression of either the TCL1 oncogene, or transcripts from its homologue
      MTCP1/c6.1B, in leukaemic and non-leukaemic T cells from ataxia telangiectasia
      patients.
AB  - Patients with the recessively inherited disorder ataxia telangiectasia (A-T) have
      a high level of specific chromosome translocations which can be easily observed
      in peripheral T cells and show a greatly increased predisposition to
      leukaemia/lymphoma, mainly of T cell origin. Some translocation cells proliferate
      into a large clone and may develop into T cell prolymphocytic leukaemia (T-PLL).
      By the time of diagnosis of T-PLL, the clone contains many more genetic changes
      in the form of additional translocations. T-PLL is also seen in non-A-T
      individuals where expression of either TCL1 (at 14q32) or the c6.1B/MTCP1 A1
      transcript (at-Xq28) has been demonstrated in just a few instances. We show here,
      that expression of TCL1 occurs in leukaemic T cells from A-T patients with
      chromosome 14 rearrangements. Expression of TCL1 also occurs in the preleukaemic
      clone cells of A-T patients containing the primary translocation alone. Some
      expression of TCL1 could also be detected in randomly selected A-T patients
      without large cytogenetic clones and without any evidence of leukaemic change. We
      also show that expression of the B1 transcript from a second gene, MTCP1,
      occurred at a relatively high level only in two T-PLL tumours from A-T patients
      with t(X;14) translocations whereas the MTCP1/A1 transcript is much more widely
      expressed in both tumour and non tumour cells of A-T and non-A-T individuals.

PMID- 8570216
TI  - The down-regulated in adenoma (DRA) gene encodes an intestine-specific membrane
      glycoprotein.
AB  - The protein product of the DRA gene, a gene whose expression is down-regulated in
      colon adenomas and adenocarcinomas, is a membrane glycoprotein and a member of a
      family of sulfate transporters. It is expressed in the intestinal tract
      (duodenum, ileum, cecum, distal colon), but not in the esophagus or stomach. DRA
      mRNA expression is restricted to the mucosal epithelium, and DRA protein
      expression is further limited to the columnar epithelial cells, particularly to
      the brush border. Consistent with its expression in the differentiated columnar
      epithelium of the adult human colon, DRA is first expressed in the midgut of
      developing mouse embryos at day 16.5, corresponding with the time of
      differentiation of the epithelium of the small intestine. A model for the
      structure of the DRA protein is proposed and its possible role in colon
      tumorigenesis is discussed.

PMID- 8570217
TI  - Tie1, a receptor tyrosine kinase essential for vascular endothelial cell
      integrity, is not critical for the development of hematopoietic cells.
AB  - The receptor tyrosine kinase Tie1 is expressed in both vascular endothelial cells
      and immature hematopoietic cells. Expression of a common signaling molecule in
      distinct cellular lineages may suggest common ancestry of these lineages in
      ontogeny and/or utilization of shared signaling pathways. Tie 1-deficient mice
      carrying a targeted insertional mutation in germ line show defects in endothelial
      cell integrity resulting in edema and hemorrhage. To analyse the potential role
      of this kinase in hematopoietic cells, we have now compared hematopoietic
      compartments in wildtype and Tiel-deficient mice. The results show: (1) Total
      cellularity is mildly reduced comparing Tie1-/- and wildtype fetal liver from day
      15.5 of gestation. (2) In vitro colony assays and cell transfer experiments of
      fetal liver cells into lymphocyte-deficient recombination-activating-gene-2-/-
      mice reveal that Tie1-/- hematopoietic progenitor cells can generate myeloid
      lineages as well as T and B lymphocytes. (3) Tie1-/- fetal liver cells contain
      long-term (at least 4 months) bone marrow-reconstituting hematopoietic stem cells
      suggesting that this kinase is not critical for stem cell-engraftment nor self
      renewal.

PMID- 8570218
TI  - Suppression of tumorigenicity and invasiveness of colon carcinoma cells by
      introduction of normal chromosome 8p12-pter.
AB  - The development of human colon carcinomas is associated with a number of genetic
      alterations. A high frequency of deletion of the short arm of chromosome 8 at a
      late stage of colon carcinogenesis was detected by DNA analysis of colon
      carcinomas, which suggests the presence of a tumor suppressor gene. We therefore,
      introduced normal human chromosome 8 into colon carcinoma cells that showed
      allele loss on 8p21, through microcell hybridization. Five clones of hybrid cells
      were obtained from independent experiments. Three hybrids exhibited morphological
      alteration and suppressed tumorigenicity in the subcutis of nude mice, but the
      other two did not. The difference between the two types of hybrids was the region
      of the introduced normal chromosome 8: Three hybrids exhibiting morphological
      alteration and suppressed tumorigenicity had the entire region of the introduced
      chromosome 8, whereas the other two, exhibiting no change, lacked 8p12-pter from
      the introduced chromosome. Furthermore, the invasiveness of the hybrids with
      suppressed tumorigenicity was reduced to one-fifth of that of the parental cells.
      These results indicate that 8p12-pter carries a gene that contributes to
      suppression of both tumorigenicity and invasiveness of colon carcinomas.

PMID- 8570219
TI  - RXR alpha is essential for mediating the all-trans retinoic acid-induced growth
      arrest of C2 myogenic cells.
AB  - In C2 muscle cells, retinoic acid (RA) induces growth arrest associated with
      terminal differentiation. These RA actions are presumed to be mediated through
      nuclear receptors (RARs and RXRs) that belong to the superfamily of ligand
      dependent transcription factors. In this study, we have characterized a myogenic
      C2 subclone, that unlike parental cells, is resistant to growth inhibition and
      differentiation by RA. Examination of these RA-sensitive and resistant C2 cells
      for the expression of retinoid acid receptors revealed a lack of RXR alpha
      expression at the myoblast stage in resistant C2 cells. To determine the
      functions of RXR alpha, we introduced an RXR alpha expression vector into RA
      resistant C2 cells by transient or stable transfections. Our results show that
      RXR alpha restores the response to RA in this subclone with respect to AP1
      inhibition and growth arrest. These observations indicate that RXR alpha plays a
      crucial role in mediating RA induced growth arrest of C2 myogenic cells.

PMID- 8570221
TI  - A novel mutation in the promotor region in a family with a mild form of
      retinoblastoma indicates the location of a new regulatory domain for the RB1
      gene.
AB  - We describe a family segregating the retinoblastoma phenotype where the affected
      individuals have only unifocal tumours and where linkage analysis has identified
      unaffected mutant gene carriers. DNA from members of this 'low penetrance'
      pedigree was subjected to an exon-by-exon SSCP analysis of the RB1 gene. No
      mutations were found in the 27 exons of the coding region but an SSCP band shift
      was seen for PCR products covering the RB1 promoter region. Sequencing identified
      a G-->C change within a GGGCGG motif which is the core of the recognition
      sequence of the SP1 transcription factor. Electromobility shift assays
      demonstrated that SP1 does not bind to oligomers from this region of the RB1
      promoter but bandshifts were seen for an, as yet, unidentified protein(s) which
      was not seen using an oligomer containing the G-->C mutation. Thus,
      identification of a naturally occurring mutation in a family with only 'mild'
      phenotypes has identified another regulatory sequence in the RB1 promoter which
      binds an endogenous cellular protein(s). Identification of this protein should
      allow a better understanding of the control of expression of the RB1 gene.

PMID- 8570220
TI  - High incidence of loss of heterozygosity and abnormal imprinting of H19 and IGF2
      genes in invasive cervical carcinomas. Uncoupling of H19 and IGF2 expression and
      biallelic hypomethylation of H19.
AB  - The few imprinted genes characterized so far include the insulin-like growth
      factor-2 gene (IGF2) coding for a foetal growth factor and the H19 gene whose
      normal function is unknown but which is likely to act as an RNA with an
      antitumour effect. IGF2 is expressed by the paternal allele and H19 by the
      maternal allele. This reciprocal expression is quite interesting because both H19
      and IGF2 genes are located close to each other on chromosome 11p15.5 in a region
      subject to loss of heterozygosity (LOH). Moreover, loss of imprinting (LOI) or
      biallelic expression has been proposed as an epigenetic mechanism for
      tumorigenesis in a variety of human cancers including Wilms' tumour. In this
      study we report the LOH, LOI and methylation status of H19 and IGF2 genes in 29
      invasive cervical carcinomas of different clinical stages. Fourteen (48%) and 13
      (45%) tumours were heterozygous for H19 and IGF2 respectively. LOH for H19 and
      IGF2 genes were found in 2 of 14 (14%) and 3 of 13 (23%) informative tumours,
      respectively. LOI of H19 and IGF2 was detected in 2 of 12 (17%) and 5 of 10 (50%)
      tumours with no LOH, respectively. More interestingly, monoallelic expression of
      the otherwise silent H19 allele (allele switch) was observed in 2 of 12 (17%)
      tumours and biallelic expression of IGF2 was detected in one specimen of normal
      cervix adjacent to the tumour. The expressing H19 allele, and to a lower degree
      also the silent allele, were hypomethylated in tumours suggesting that
      demethylation of both H19 alleles may be associated with an early step of
      imprinting alteration. In cervical cancer H19 and IGF2 expressions could be
      independently regulated. In conclusion, our data suggest that H19 and IGF2 genes,
      via deletions and/or abnormal imprinting, could play a crucial role in a large
      proportion (58%) of cervical cancers where they may be associated with disease
      progression.

PMID- 8570222
TI  - Detection and subcellular localization of an AML1 chimeric protein in the t(8;21)
      positive acute myeloid leukemia.
AB  - AML1, a gene encoding a protein of the PEBP2/CBF family of transcription factors
      is disrupted by translocations associated with human leukemia. In the t(8;21)
      acute myelogenous leukemia (AML), AML1 was found fused to a gene on chromosome 8
      that we designated CDR (also known as ETO and MTG8). Immunoprecipitation
      experiments followed by immunoblotting using a combination of antibodies against
      different epitopes of one of the predicted chimeric proteins encoded by a fully
      characterized fusion transcript enabled us to visualize a chimeric protein in the
      t(8;21) Kasumi-1 cell line. The estimated size of this protein is 64 kDa.
      Immunoblotting of leukemic blasts containing the t(8;21) detected a protein of
      the same size. Immunofluorescence experiments indicate that the chimeric protein
      is localized in the nucleus. A normal AML1 protein of 27 kDa was also detected in
      t(8;21) Kasumi-1 cells. It remains to be established by which mechanism the
      mutant AML1 isoform may contribute to the leukemogenesis process of t(8;21)
      positive acute myeloid leukemia.

PMID- 8570223
TI  - Overexpression of RelB in transgenic mice does not affect I kappa B alpha levels:
      differential regulation of RelA and RelB by the inhibitor protein.
AB  - In mouse lymphoid tissues, RelB heterodimers represent the constitutive kappa B
      binding activity, whereas RelA and c-Rel complexes most likely are involved in
      inducible kappa B-binding and gene activation. Our laboratory has previously
      shown that the potential excess of NF-kappa B activity in transgenic mice
      overexpressing RelA is counteracted by a dramatic increase in I kappa B alpha,
      mainly due to its increased stability through association with RelA. As an
      attempt to elucidate the in vivo mechanisms that lead to the constitutive DNA
      binding activity of RelB heterodimers, we have generated mouse lines
      overexpressing a relB transgene in a position-independent and copy number
      dependent manner. Expression of RelB in these transgenic animals is very high in
      immature thymocytes and restricted to T cell areas in secondary lymphoid tissues.
      In contrast to the results obtained with RelA-transgenic thymocytes, we
      demonstrate here that overexpression of RelB results in a dramatic increase in
      overall kappa B-binding activity. Interestingly, I kappa B alpha protein levels
      are not altered in the RelB-transgenic animals, indicating that within the same
      cell type RelA and RelB complexes are differentially regulated by I kappa B
      alpha.

PMID- 8570224
TI  - Mutational analysis of the p16 family cyclin-dependent kinase inhibitors p15INK4b
      and p18INK4c in tumor-derived cell lines and primary tumors.
AB  - The growth suppressing activity of the retinoblastoma suspectibility gene
      product, pRb, is down regulated by cyclin-dependent kinases 4 and 6 (CDK4 and
      CDK6) whose kinase activity is negatively regulated by CDK inhibitors of the p16
      family. We have examined the genomic status of two recently isolated p16-related
      CDK inhibitors, p15 and p18, in 15 normal and 73 tumor-derived cell lines
      established from 23 different tissues, as well as 26 invasive primary breast
      cancers and 20 acute myelogenous leukemias. p15 was found to be homozygously
      deleted in 22% of the tumor derived cell lines, but no point mutations were found
      in either the cultured cells or the two types of primary tumors. With the
      exception of one breast cancer cell line, no deletions or mutations were found in
      the p18 gene in either cultured cell lines or primary tumors. These results
      indicate that mutation of the p18 gene occurs rarely in human tumors. Thus, while
      they share a very similar biochemical mechanism of inhibiting the kinase activity
      of CDK4 and CDK6, members of the p16 gene family play different roles in
      controlling cell proliferation and suppressing tumor growth.

PMID- 8570225
TI  - Retinoic acid-induced growth arrest and differentiation of neuroblastoma cells
      are counteracted by N-myc and enhanced by max overexpressions.
AB  - N-myc expression is negatively regulated by retinoic acid (RA) which induces the
      growth arrest and differentiation of neuroblastoma (NB) cells. However, it has
      not been completely defined whether N-Myc promotes growth and/or antagonises
      neuronal differentiation of NB cells or whether the down regulation of N-myc
      occurs as a consequence of the onset of differentiation. By transfecting an N-myc
      gene construct into these cells, we found that the constitutive overexpression of
      N-myc stimulated proliferation in RA containing medium and, although these cells
      were still responsive to RA, they were no longer able to differentiate. Since N
      Myc functions appear to be mediated by heterodimerization with Max, the ectopic
      overexpression of max in NB cells was also investigated. In contrast to N-Myc,
      Max strongly induced the differentiation by enhancing the effects of RA. Max
      transfected cells rapidly arrested growth and differentiated fully within a few
      days of RA treatment. These findings suggest that the relative levels of N-Myc
      compared to Max appears to be crucial in stimulating neuroblastoma growth or
      differentiation, and may contribute to explain the remarkable clinical behaviour
      of neuroblastomas.

PMID- 8570226
TI  - Centennial celebration of otolaryngology-head and neck surgery in the United
      States: history of the American Academy of Otolaryngology-Head and Neck Surgery.

PMID- 8570227
TI  - Bilateral lateral rhinotomy for resection of bilateral inverted papilloma.

PMID- 8570228
TI  - Cryptococcosis of the larynx.

PMID- 8570229
TI  - Intradiploic arachnoid cyst presenting as a frontal sinus mass.

PMID- 8570230
TI  - Intranasal presentation of condyloma acuminatum.

PMID- 8570231
TI  - Lateral basal encephalocele of the infratemporal fossa.

PMID- 8570232
TI  - Use of the melolabial flap in intraoral reconstruction.
AB  - Functional reconstruction of the oral cavity after tumor ablation is challenging.
      A variety of methods are available for reconstruction including primary closure,
      skin grafts, local cutaneous flaps, musculocutaneous flaps, and free flaps.
      Appropriate reconstruction addresses the size, location, and tissue needs of the
      defect. The melolabial flap allows for reliable and effective intraoral
      reconstruction with minimal donor morbidity, making it ideal for select defects.
      From 1989 to 1993 16 patients aged 51 to 81 years underwent reconstruction of
      intraoral defects with 24 melolabial flaps. Twenty-two flaps survived without
      complication and two flaps failed, for success rate of 91.7%. The two failed
      flaps occurred in the same patient. Of the remaining patients 8 had prior
      radiation therapy and 11 had prior or concomitant neck dissections. The flaps
      were used to reconstruct 13 floor-of-mouth, 1 buccal mucosa, 1 retromolar
      trigone, and 1 gingival defect. We conclude that the melolabial flap is ideal for
      select intraoral defects.

PMID- 8570233
TI  - Magnetic resonance imaging in the evaluation of Langerhans' cell histiocytosis of
      the temporal bone: case report.

PMID- 8570234
TI  - Value of magnetic resonance angiography in the evaluation of head and neck
      neoplasms.

PMID- 8570235
TI  - Dedifferentiation of primary squamous cell carcinoma arising from the nasal
      septum.

PMID- 8570236
TI  - Microsporidial rhinosinusitis: is this the next pathogen to infect the sinuses of
      the immunocompromised host?

PMID- 8570237
TI  - Polyostotic eosinophilic granuloma in an infant.

PMID- 8570238
TI  - Postoperative carotid artery rupture caused by actinomyces infection.

PMID- 8570239
TI  - Minimizing pectoralis myocutaneous flap loss with the delay principle.

PMID- 8570240
TI  - HIV-related Pneumocystis carinii thyroiditis: a unique case and literature
      review.

PMID- 8570241
TI  - Nonpulmonary sinonasal sarcoidosis with intracranial invasion.

PMID- 8570242
TI  - Waardenburg syndrome.

PMID- 8570243
TI  - Comments on the symptom of "dizziness" and vestibular science.

PMID- 8570244
TI  - Vocal fold paralysis in infants twelve months of age and younger.
AB  - Seventeen cases of unilateral or bilateral vocal fold paralysis were diagnosed in
      infants younger than 12 months from 1991 to 1994 at the University of Iowa
      Hospitals and Clinics. Eight (47%) children with left vocal fold paralysis had a
      history of prior thoracic surgery--two to repair complex congenital anomalies and
      six to ligate a patent ductus arteriosus. During the study period, a total of 81
      patent ductus arteriosus ligations were performed, yielding a 7.4% postoperative
      incidence of vocal fold paralysis. Seven (41%) children had idiopathic vocal fold
      paralysis (3 right, 1 left, 3 bilateral). Two (12%) children had VFP caused by
      central nervous system pathology (1 right, 1 bilateral). Tracheotomy was not
      required in any case. Prognosis for vocal fold paralysis varied with cause. With
      left vocal fold paralysis caused by thoracic surgery, no improvement was noted
      after an average follow-up of 6 months; with idiopathic vocal fold paralysis
      infants improved within an average of 6 weeks of diagnosis; with vocal fold
      paralysis caused by central nervous system pathology, treatment of the underlying
      condition was followed by return of vocal cord function. Irrespective of cause,
      the morbidity associated with vocal fold paralysis is minimal. Although
      tracheotomy is not required, careful airway observation is important. Differences
      and similarities of these results with other studies are discussed.

PMID- 8570245
TI  - Correlates of cochlear implantation, 1986-1992.
AB  - There is a paucity of information regarding the use of cochlear implants within
      large populations. This article describes correlates of cochlear implantation
      procedures using a statewide hospital discharge database. Among the 146 implant
      procedures, 55% involved female patients, whereas the largest groups of patients
      were represented by younger and older persons (27% between ages 2 and 9 years and
      24% 60 years and older). A bimodal distribution was apparent for average annual
      age-specific rates of cochlear implantation, with the highest rates among persons
      aged 2 to 9 years (5.4 implants per 1 million) and persons aged 60 to 69 years
      (3.7 implants per 1 million). Total hospital charges, excluding professional
      fees, exceeded $12,000 per implant and were found to vary significantly when
      examined by length of stay and by calendar year of procedure. The data presented
      are unique with regard to the total number of cochlear implant procedures
      included and the large, diverse population used. This study expands knowledge
      concerning the epidemiology and utilization of cochlear implantation.

PMID- 8570246
TI  - An objective evaluation method for facial mimic motion.
AB  - This technique was designed to establish a simple, objective evaluation system
      for facial paralysis through the use of a personal computer. A total of 24 marks
      were placed on the faces of subjects for the following procedures. Movements of
      the face were photographed with a video-camera and fed continuously into the
      computer. Ten frames per movement representing facial movement from rest to
      maximum movement were selected for analysis. By means of a digital image
      processing technique, only the marks placed on the face were extracted, and the
      movement of these marks was quantitatively analyzed. A total of 44 healthy
      subjects with no history of facial paralysis were used as a normal control group.
      The patients with facial paralysis consisted of nine subjects with Bell's palsy
      and three with Ramsay Hunt syndrome. In the eye-closing motions, no significant
      differences were found between the sum of the movement distances on the left and
      right sides in each normal subject. However, the patients with facial paralysis
      showed distinct differences from those obtained in the normal subjects. The
      improvement process was also evaluated with a ratio of affected- and normal-side
      facial movements.

PMID- 8570247
TI  - Hearing results after posterior fossa vestibular neurectomy.
AB  - The effect of posterior fossa vestibular neurectomy on postoperative hearing
      levels of 172 patients was studied at 1 week, 1 month, 1 year, and 18 to 24
      months. According to the 1985 American Academy of Otolaryngology-Head and Neck
      Surgery guidelines for reporting treatment outcome, 66% of patients had improved
      or unchanged hearing at 18 to 24 months. One-week postoperative hearing was
      poorer than at 1 month or later follow-up. Permanent profound hearing loss
      occurred in 4.7% of patients. In patients who had worse than 80 dB pure-tone
      average and 20% speech discrimination score hearing loss before surgery, 68%
      improved above this hearing level, and 16% improved to better than 50 dB pure
      tone average and 50% speech discrimination after surgery. This suggests that it
      may be worthwhile to preserve the cochlear nerve in certain patients who may
      otherwise be candidates for labyrinthectomy. These hearing results are comparable
      with other treatment modalities including endolymphatic sac surgery.

PMID- 8570248
TI  - Accuracy of high-resolution computed tomography in cochlear implantation.
AB  - Multichannel cochlear implants are a proven method for the auditory
      rehabilitation of individuals who have severe-to-profound sensorineural hearing
      loss. These devices typically require insertion into the scala tympani of the
      cochlea to provide auditory stimulations. A patent scala provides the best chance
      for an adequate insertion of the electrode array. Preoperative high-resolution
      computed tomography imaging has traditionally been used to determine the patency
      of the scala tympani. Its ability to accurately predict the patency of the
      cochlea has been questioned in several retrospective studies. A prospective study
      was undertaken in 28 consecutive individuals undergoing cochlear implant surgery
      to compare the findings on high-resolution computed tomography with the surgical
      findings in an attempt to determine high-resolution computed tomography's
      accuracy. Cochlear obstruction caused by ossification was accurately predicted in
      six of six individuals but overestimated in the round window region in three
      individuals. High-resolution computed tomography accurately predicted patent
      cochleas in 19 individuals. No false-negative results were encountered. In this
      study sensitivity of high-resolution computed tomography was 100%, and
      specificity was 86%. High-resolution computed tomography appears to be more
      helpful than previously reported for determining cochlear patency.

PMID- 8570249
TI  - Systematic approach to electrode insertion in the ossified cochlea.
AB  - Ossification of the fluid spaces of the cochlea occurs often in candidates for
      cochlear implantation, especially children. When noted before surgery on
      computerized tomography, ossification previously was thought to contraindicate
      cochlear implantation because of possible mechanical obstruction and uncertainty
      about the level of function that could be achieved by stimulating an ossified
      cochlea. However, during the preceding 6 years, techniques have been developed
      that permit implantation in ossified cochleas. We present a systematic approach
      that has been developed to treat the three clinically important categories of
      cochlear ossification: round window niche obliteration, inferior segment
      obstruction, and upper segment obstruction. Case reports are presented for each
      of these three drill-out procedures, demonstrating results often similar to those
      expected for implantation of the nonossified cochlea.

PMID- 8570250
TI  - Otocephalus: histopathology and three-dimensional reconstruction.
AB  - Otocephaly is a lethal malformation of the first and second branchial arches,
      which consists of ventromedial displacement of the external ear structures
      (synotia), mandibular aplasia (agnathia), absence of the tongue (aglossia), and
      microstomia. We present the first complete description of the temporal bone
      findings in a case of otocephalus. A three-dimensional computer-assisted
      reconstruction of the right temporal bone was performed, allowing a unique
      graphic analysis. An extremely low-lying middle fossa tegmen was noted with
      malrotation of the middle ear structures. Severe ossicular malformations were
      also found. An anomalous course of the internal carotid artery was noted with
      indentation of the basal turn of the cochlea. All three layers of the otic
      capsule were incompletely developed. Cochlear bony dehiscences were noted. These
      findings are consistent with early arrest of fetal development and malrotation
      caused by lack of growth pressure from the mandibular arch. Implications of these
      findings in the embryologic development of the ear are discussed.

PMID- 8570251
TI  - Morphogenesis of the lateral nasal wall from 6 to 36 weeks.
AB  - This research describes the development of the lateral nasal wall, the
      description of which will allow a better comprehension of its anatomic
      complexity. One hundred embryos and fetuses from the sixth to thirty-sixth weeks
      of morphologic age were studied. The seventh week shows the first buds of the
      three turbinates. At the ninth week the precartilaginous nucleus of the inferior
      turbinate is observed. Likewise, at the tenth week the uncinate process appears,
      and the invagination of the epithelium begins the formation of the infundibulum
      and the maxillar sinus. At the fourteenth week the cartilaginous nasal capsule is
      present. The epithelium is invaginated, starting the formation of the ethmoid
      cells. During the seventeenth week of development the invagination of the mucus
      has invaded the maxillar bone, which constitutes the maxillar sinus. At the
      thirty-sixth week the lateral nasal wall is well developed. In 23 fetuses the
      supreme turbinate (fourth) was found. Although the length of the lower three
      turbinates increased progressively and proportionally in intrauterine life
      without differences between the sexes, the fourth remains invariably at an
      average length of 5 mm from the fourteenth to the thirty-sixth and was present in
      65% of male fetuses.

PMID- 8570252
TI  - Comparison of the canalith repositioning procedure and vestibular habituation
      training in forty patients with benign paroxysmal positional vertigo.
AB  - Forty patients with benign paroxysmal positional vertigo were treated with either
      the canalith repositioning procedure or vestibular habituation exercises to
      determine which treatment approach would be most effective. Twenty additional
      patients with benign paroxysmal positional vertigo were not treated and served as
      a control group. The intensity and duration of symptoms were monitored during a 3
      month period. All patients had symptomatic relief in the treated groups. The
      canalith repositioning procedure seemed to give resolution of symptoms with fewer
      treatments, but long-term results show either treatment approach is effective in
      relieving positional vertigo. A significant number of patients in the control
      group (75%) continued to have vertigo. Advantages and disadvantages of the
      canalith repositioning procedure and vestibular habituation exercises are
      discussed.

PMID- 8570253
TI  - Extracapsular spread in the clinically negative neck (N0): implications and
      outcome.
AB  - Cervical metastasis is the most important prognostic factor in head and neck
      cancer patients. The prognostic significance of extracapsular spread of tumor in
      metastatic lymph nodes has also been documented. The presence of extracapsular
      spread further reduces the survival by 50% in those patients with cervical
      metastatic disease. Most patients with clinically negative necks (stage N0) have
      a good prognosis. However, some of these patients will have neck disease and
      distant metastasis and will eventually die. Because the presence of extracapsular
      spread is a predictor of poor outcome, we hypothesized that extracapsular spread
      may be a factor in the subset of patients with clinically negative necks who have
      poor outcomes. One hundred nine patients with clinically negative necks who had
      undergone neck dissection were identified. Occult metastasis was observed in 34%
      of patients. In this group, extracapsular spread was present in 18 (49%)
      patients. Overall, 103 patients were evaluable, of whom 70 (68%) remain free of
      disease 2 or more years after treatment. A subgroup of 68 patients had
      histologically negative nodes, of whom 56 (82%) are free of disease. Of patients
      with extracapsular spread, only 5 (31%) of 16 are free of disease. This is in
      contrast to patients with metastasis confined to the lymph node, of whom 9 (47%)
      of 19 are free of disease. Statistical analysis of these data shows that for this
      sample size this difference is significant. The addition of radiation therapy did
      not improve outcome in these patients. Extracapsular spread predicts a worse
      outcome in patients with subclinical cervical metastasis. Alternative modes of
      adjuvant therapy are suggested because of the poor results of postoperative
      radiation therapy in patients with extracapsular spread.

PMID- 8570254
TI  - Fast spin echo magnetic resonance imaging: clinical application in screening for
      acoustic neuroma.
AB  - The advent of magnetic resonance imaging has greatly improved our ability to
      diagnose acoustic tumors, but it is a relatively expensive imaging modality. In
      the present climate of medical cost restraints, methods that reduce costs but
      maintain quality are extremely desirable. We report a new magnetic resonance
      imaging technique that uses fast spin echo without gadolinium. It provides
      ultrahigh-resolution images of the internal auditory canal and cerebellopontine
      angle. The sensitivity of this technique for the detection of acoustic tumors is
      equivalent to conventional gadolinium-enhanced magnetic resonance imaging, but
      the global cost is comparable with that of brain stem audiometry. In our practice
      fast spin echo magnetic resonance imaging has replaced brain stem audiometry as a
      screening modality to evaluate most acoustic tumor suspects. Also, the intricate
      detail of the internal auditory canal anatomy provided by this technique is
      useful in planning surgical removal of acoustic tumors.

PMID- 8570255
TI  - Heat shock proteins in middle ear cholesteatoma.
AB  - Heat shock proteins (HSPs), particularly HSP60 and HSP70, may have integral roles
      in several aspects of the pathogenesis of acquired cholesteatoma. Cholesteatoma
      is usually associated with an inflammatory reaction occurring in the middle ear
      cavity, leading to proliferation, differentiation, and programmed cell death of
      keratinocytes. The presence of HSP60 and HSP70 in cholesteatoma was demonstrated
      by the immunoblotting assay with specific anti-HSP60 and anti-HSP70 antibodies
      after protein extraction. The distribution of HSP60 and HSP70 in the
      cholesteatoma tissues was studied immunohistochemically with paraffin-embedded
      sections. HSP60 and HSP70 appeared to be localized in the cytoplasm of
      keratinocytes in all layers of the epithelium of cholesteatoma. Moreover, HSP70
      was found in the nucleus of keratinocytes. Both HSPs were not labeled in the
      epidermis of the external ear canal skin or normal facial skin, except for
      significant staining on keratinocytes of hair follicles in facial skin. High
      density of HSP60 and HSP70 may be induced by the inflammatory reaction and immune
      responses in the middle ear cavity during the clinical development of
      cholesteatoma. Induction of HSP60 and HSP70 in cholesteatoma epithelium may also
      be related to hyperproliferation and active differentiation of basal
      keratinocytes, which cause the accumulation of keratin debris, a characteristic
      feature of cholesteatoma. In the nucleus of keratinocytes, HSP70 may act to
      stabilize p53 protein, which functions as a negative regulator of cellular
      proliferation and is crucial to apoptosis of keratinocytes. This study
      demonstrates HSPs in cholesteatoma and suggests important roles for HSPs in the
      clinical development of cholesteatoma.

PMID- 8570256
TI  - Effect of a second laryngeal stimulation during recovery from the laryngeal
      chemoreflex.
AB  - The laryngeal chemoreflex is a potential mechanism for sudden infant death. In
      experimental protocols in which a full recovery is allowed between stimuli, no
      laryngeal chemoreflex responses result in a fatal outcome. In the clinical
      situation there are no controls to prevent repeated laryngeal stimulation before
      a full recovery. The effect of a laryngeal stimulus applied during or soon after
      a laryngeal chemoreflex-induced apnea was investigated. Eighteen piglets were
      divided into groups aged 10 to 12 days, 17 to 21 days, and 32 to 36 days.
      Laryngeal stimulation was performed under normoxic conditions with water applied
      to the mucosa. Baseline respiratory and cardiovascular response data were
      measured. After recovery an initial stimulation was applied, followed by a second
      stimulation during the apnea or 5, 30, 60, or 120 seconds after restoration of
      breathing. No profound apneas occurred with baseline laryngeal stimulation. In
      piglets aged 32 to 36 and 17 to 21 days, a second laryngeal stimulus resulted in
      a shortened apnea duration. The response varied in piglets aged 10 to 12 days
      with profound apneas observed in 2 of 6 subjects and 4 of 30 trials. Piglets aged
      17 to 36 days are less susceptible to the laryngeal chemoreflex during the
      immediate recovery period. In piglets aged 10 to 12 days, the laryngeal
      chemoreflex response may be more severe after a second stimulus.

PMID- 8570257
TI  - Transsphenoid endoscopic management of petrous apex cholesterol granuloma.

PMID- 8570258
TI  - Fourth branchial cleft cysts.

PMID- 8570259
TI  - Infantile fibrosarcoma in the nasal cavity.

PMID- 8570260
TI  - [Degeneration of catecholaminergic neurons].

PMID- 8570261
TI  - [HCV antibodies in hemodialyzed patients in Tunisia].
AB  - The prevalence of seropositivity to Hepatitis C and B virus and HIV infection in
      Haemodialysis patients was assessed in sera from 235 patients from 6 dialysis
      units in Tunisia. Anti-HCV antibodies were found in 106 patients (45.10%), the
      hepatitis B surface antigene was found in 19 patients (8%), and no case of HIV
      infection was found. Anti-HCV positivity was correlated with duration of dialysis
      (p < 0.001). There was no correlation between anti-HCV positivity and the number
      of transfusions.

PMID- 8570262
TI  - [Expression of the c-erbB-2 oncoprotein in mammary Paget's disease.
      Immunohistochemical study by using 3 antibodies].
AB  - An overexpression of the c-erbB-2 oncoprotein has been demonstrated in the breast
      cancer and has been associated with a poor prognosis. Our study involved 23 cases
      of mammary Paget's disease which was found to be associated with the intraductal
      carcinomas in 13 cases, the intraductal carcinomas supposed micro-invasive in 2
      cases, the infiltrating ductal carcinomas with predominant intraductal component
      in 6 cases and the infiltrating ductal carcinomas in 2 cases. The presence of c
      erbB-2 oncoprotein has been determined immunohistochemically with 3 different
      antibodies: rabbit anti-human c-erbB-2 oncoprotein A485 (Dako), c-erbB-2
      oncoprotein (internal domain) mouse monoclonal antibody NCL-CB11 (Novocastra),
      and c-erbB-2 oncoprotein (external domain) mouse monoclonal antibody NCL-CBE1
      (Novocastra). An overexpression of the c-erbB-2 oncoprotein has been observed in
      21 of the 23 studied cases. We noted an intense membrane staining in the
      intraepidermal or intraglandular tumour cells of mammary Paget's disease. Any
      staining has been observed in 2 cases with glandular component of pure
      intraductal type. These results are identical whatever the antibody used. In a
      previous study concerning mammary Paget's disease, it has been noted a
      correlation between this overexpression and presence of large malignant cells. We
      also have found this notion in mammary Paget's disease where the c-erbB-2
      positive neoplastic cells in the different tumour components were large with
      prominent cytoplasm. The obtained results argue strongly for adenocarcinomatous
      origin for mammary Paget's disease and exhibit that the overexpression of c-erbB
      2 oncoprotein was not constantly in correlation with a poor prognosis.

PMID- 8570263
TI  - [Assessment of the role of enterocyte ion exchange in the intestinal absorption
      of amoxicillin, based on a study of the interaction with amiloride].
AB  - Intestinal dipeptide carrier system has been shown in vitro to be involved in
      intestinal absorption of betalactam antibiotics. Given that efficiency of this
      transport system depends on a pH gradient (extracellular pH < intracellular pH)
      at the brush-border membrane of enterocytes, we assessed the effects of
      amiloride, a known inhibitor of the Na-H exchange, on the bioavilability of oral
      amoxicillin in eight normal volunteers. Following a single 10 mg oral dose of
      amiloride, the absolute bioavailability of oral amoxicillin turned out to
      decrease by 27% (p < 0.01). The extent of reduction of oral amoxicillin AUC
      appeared to significantly correlate (p = 0.005) with the extent of decrease in
      potassium renal excretion but not with variations in antibiotic renal clearance
      under amiloride effect. Such patterns seem to confirm in vivo the role of the Na
      H exchange in betalactam absorption and to suggest the underlying regulatory
      function of intracellular Na concentration, the latter depending on the (NaK)
      ATPase activity.

PMID- 8570264
TI  - [A new mode of expression for the assessment of capacities of DNA repair by flow
      cytometry].
AB  - Flow cytometry technic was used to study DNA synthesis of Hep G2 cells following
      mitomycin C and adriblastine treatments during 24 hours. DNA synthesis was
      expressed by 2 methods: the new expression global DNA synthesis (S+G2)/G1 that
      considered the cells during scheduled and unscheduled DNA syntheses of S and G2
      phases and the cell cycle (Fox program) that evaluated the cells during scheduled
      DNA synthesis by the terms G1 = 2n, S = 2n+x and G2 = 4n which excluded
      unscheduled DNA synthesis. The experimental data treated with this new expression
      led to the determination of threshold concentrations for the two tested compounds
      where the DNA repair mechanisms were overloaded, leading to cell death. This term
      was shown to be more accurate to describe the genotoxic action of compounds.
      Furthermore, these threshold concentrations of DNA damages was found to be linked
      with significant increase of micronuclei in the micronucleus test.

PMID- 8570265
TI  - [Adenoviruses from stool samples in hospital units. Comparison with main
      pathogens in gastroenteritis (rotavirus, Campylobacter, Salmonella)].
AB  - During a six-years period (1988-1993), a total of 14,644 stool samples from in
      patients of Limoges University Hospital were examined for the presence of
      principal enteric pathogens, such as adenovirus, rotavirus, Campylobacter,
      Salmonella, Shigella and others. Stools were processed for identification of
      bacteria by standard methods and viruses were detected in fecal specimens using
      antigen detection methods: ELISA (Enzyme Linked Immunosorbent Assay) and latex
      agglutination test. The decreasing rates of presence of enteric agents were
      respectively 6% for rotavirus, 3.2% for Salmonella, 2% for adenovirus, 1.6% for
      Campylobacter and 0.2% for Shigella, but according to the lack of sensibility of
      latex agglutination test, adenovirus prevalence was probably underestimated.
      Concerning the distribution of enteric pathogens throughout the year, our data
      demonstrate that rotavirus were rather shed during the months from January to
      April, adenovirus between April and August, Campylobacter during summer and
      Salmonella from July to October. The two thirds of Campylobacter and rotavirus
      infections and the half of adenovirus and Salmonella infections were identified
      during the ten first years of life. The highest prevalence occurs before 5 years
      old, during the 2nd year of life for adenovirus (4.4%) and rotavirus (22.3%) and
      during the 3rd year of life for Campylobacter (6.84%) and Salmonella (8.6%).

PMID- 8570266
TI  - [Tools for the assessment of tobacco dependence: comparison with questionnaires
      and marker assays].
AB  - Fagerstrom Tolerance Questionnaire has been questioned in some respects for the
      purpose of the evaluation of tobacco dependence. In a sample of 208 smokers
      attempting to quit, we measured on urinary samples the levels of nicotine
      metabolites via their thiobarbituric acid derivatives comparatively to the levels
      of nicotine and cotinine by high performance liquid chromatography. Urinary
      concentration of nicotine metabolites was 77.1 +/- 50.0 mumol/l. Nicotine and
      cotinine levels were respectively 8.2 +/- 12.0 mumol/l and 12.9 +/- 9.8 mumol/l.
      Spearman correlation coefficients were used to examine the relationships among
      various measures of exposure to cigarette smoke, tobacco markers and tobacco
      addiction scores obtained through the Fagerstrom Questionnaire and a Simplified
      Questionnaire. Nicotine metabolites are correlated with the score obtained with
      the Simplified Questionnaire (rho = 0.39) better than with the score of
      Fagerstrom (rho = 0.28) (p < 0.01). These moderate correlations suggest that the
      measurement of tobacco markers provide a more valuable information than
      questionnaires for the appreciation of the depth of tobacco intake. The
      questionnaires should not serve as a substitute for tobacco markers
      determination.

PMID- 8570267
TI  - New World tegumentar leishmaniasis: chemotherapeutic activity of rifampicin in
      humans and experimental murine model.
AB  - Daily doses of 0.5 mg of rifampicin given intraperitoneally to mice after a
      challenge dose of 104 amastigotes of L. amazonensis led to a significant
      reduction of the size of local lesions. On the other hand, daily doses of 20
      mg/kg to children or 1200 mg to adult patients infected with L. braziliensis did
      not bring any sign of improvement after 30 days of treatment. Our results
      formally contradict rifampicin as an alternative drug in Leishmania braziliensis
      infections.

PMID- 8570268
TI  - Improved glutaminate-starch-penicillin agar for the isolation and enumeration of
      Aeromonas hydrophila from seawater by membrane filtration.
AB  - Glutaminate-starch-penicillin agar (GSP) in its original formula was found
      unsatisfactory for the detection and the enumeration of Aeromonas hydrophila from
      seawater by membrane filtration. It was also the case when GSP agar was adjusted
      to pH 8 or when ampicillin (10 mg/L) was incorporated to the original formula.
      The elevation of pH to 8 together with the addition of 10 mg/L ampicillin gave to
      the medium a high selectivity and permitted the detection of A. hydrophila from
      seawater. The numbers of A. hydrophila were monitored at 11 beaches along the
      coastline of Patras and the distribution of Aeromonas was not found homogenous.
      Low numbers of A. hydrophila were isolated from most samples tested, whereas high
      concentrations of A. hydrophila were isolated specifically from samples that were
      collected near sewage and fresh water inputs.

PMID- 8570269
TI  - [Regulation of the expression of HLA class I genes in human trophoblasts].
AB  - This article presents an overview of the more recent data dealing with the
      constitutive expression of classical HLA-A, -B, -C and nonclassical HLA-E, -F, -G
      class I genes in the different trophoblast cell subpopulations that constitute
      the materno-fetal interface during human pregnancy. Although transcribed,
      classical HLA class I genes are never expressed as membrane-bound products in any
      of the trophoblast cell subpopulations. On the contrary, HLA-G is expressed at
      the cell surface of extravillous cytotrophoblast cells from first trimester
      placenta, suggesting that it may play a role in the maternal tolerance against
      the fetal allograft. Molecular regulatory mechanisms that may control such
      differential expression of classical and nonclassical class I molecules,
      according to the cell type, state of differentiation and stage of gestation are
      also examined. They may operate at the levels of transcription (cis- and/or trans
      acting mechanisms), translation and/or transport of HLA class I heavy chains to
      the cell surface.

PMID- 8570270
TI  - [The discovery of thrombopoietin].

PMID- 8570271
TI  - [Structure of chromatin and cell cycle. 3].
AB  - During the cell cycle, chromatin undergoes structural changes associated with
      cellular functions such as DNA replication during the S phase or the
      transcriptional inactivation during metaphase. All levels of chromatin
      organization from the nucleosome to the loops attached to the scaffold are
      concerned by these changes. Biochemical or biophysical studies from 70's, as well
      as more recent studies using nondestructive in situ methods, that allow to obtain
      information at the individual cell level, tend to demonstrate a correlation
      between the condensation state of the chromatin and the position of the cell in
      the cycle. The majority of these studies confirm the existence of one single
      cycle of condensation-decondensation for the chromatin. These studies are
      discussed in the first part of this chapter. In the second part, the role of the
      cdc (cell division cycle) gene's products in the control of the cell cycle and in
      the regulation of the chromatin structure are analyzed.

PMID- 8570272
TI  - Peripheral nerve sheath neoplasms. Clinicopathologic and immunochemical
      observations.

PMID- 8570273
TI  - Pandora's box or Ariadne's thread? Definition and prognostic significance of
      microinvasion in the uterine cervix. Squamous lesions.

PMID- 8570274
TI  - Papillomas of the breast. A histologic spectrum including atypical hyperplasia
      and carcinoma in situ.
AB  - We have illustrated intraductal papillomas that have a variety of alterations not
      found in "ordinary" or typical papillomas. Many of these changes are
      indistinguishable from ductal carcinoma in situ. A priori, one might expect that
      patients with papillomas associated with changes identical to ductal carcinoma in
      situ would be at an increased risk for subsequent invasive carcinoma. We suspect
      that there is an increased risk based on the fact that seven of our 26 cases (27
      percent) had fully diagnostic ductal carcinoma in situ or invasive carcinoma in
      the breast. However, the degree of increased risk has not been definitely
      established.

PMID- 8570275
TI  - Endometrial cytology by direct sampling. Its value and limitations in the
      diagnosis of endometrial lesions.

PMID- 8570276
TI  - Hepatitis C virus infection in liver allografts.
AB  - HCV infection occurs de novo in 10 percent of liver transplant recipients,
      reflecting transmission of the virus by the donor organ or blood transfusions. A
      much more common scenario, however, is recurrent allograft infection following
      liver transplantation for HCV-associated end-stage liver disease. Removal of the
      native liver in this clinical setting does not lead to eradication of infection.
      The virus persists in the blood and subsequently replicates under
      immunosuppression, resulting in a positive PCR test for HCV in most patients
      following transplantation. Clinically significant hepatitis develops in 44
      percent of patients at the University of Pittsburgh, but the reported incidence
      worldwide varies from 32 to 100 percent. Most patients show mild to moderately
      active disease, but in our experience, approximately 10 percent of patients
      develop progressive liver damage evolving into cirrhosis. The 3-year graft
      survival at Pittsburgh after a mean follow up period of 20 +/- 14 months is 68
      percent, which compares with 82 percent graft survival for patients transplanted
      for diseases other than HCV. The long-term consequences of allograft HCV
      infection are not yet completely defined, but HCV-associated cirrhosis remains a
      valid indication for liver transplantation.

PMID- 8570277
TI  - Applications of fluorescent in situ hybridization (FISH) to genetic analysis of
      human tumors.

PMID- 8570278
TI  - Update of immunocytochemistry in cytopathology.

PMID- 8570279
TI  - Gaetano Giulio Zumbo. The founder of anatomic wax modeling.

PMID- 8570280
TI  - Diagnostic problems in the spleen.

PMID- 8570281
TI  - Role of cytology in intraoperative diagnosis. A practical guide.

PMID- 8570282
TI  - Some reflections on the history, and presence of quantitative pathology.
AB  - The quantitative approach has always been present in pathology, but this approach
      is now practiced more often and in more numerous fields than before. Today
      pathology is applying DNA cytometry, morphometry, stereology, and quantitative
      immunohistochemistry, all less useful or useless without the quantitative
      approach. The present fast development of computerized instrumentation has much
      helped in the spread and application of quantitative principles.

PMID- 8570283
TI  - Diagnostic and prognostic decision support systems.
AB  - Diagnostic decision support systems provide a quantitative evaluation of
      diagnostic evidence and the capability to combine diagnostic evidence in such a
      manner that a numeric measure of certainty in a final diagnostic recommendation
      results. Generally, expert systems serve to establish a diagnostic decision,
      inference networks allow a detailed analysis of the diagnostic value of
      diagnostic clues, case-based reasoning systems are designed to provide a
      prognostic assessment targeted to an individual patient. In all of these systems,
      symbolic information, i.e., traditional diagnostic, linguistic terms and concepts
      are processed and quantitatively evaluated.

PMID- 8570284
TI  - Clinical applications of Bayesian belief networks in pathology.
AB  - Bayesian belief networks (BBNs) are a novel tool for representing knowledge about
      diagnostic decision making and for obtaining a numerical measure of certainty in
      the final diagnosis. Belief networks have been applied to the pathological
      assessment of breast, prostate and skin lesions and have been shown to provide
      consistency in the grading of microscopic features and improve diagnosis. These
      applications are reviewed in the current paper. The application of BBNs has been
      further facilitated through the use of standardised imagery which is stored
      digitally and used to enter evidence into a BBN. It is predicted that the further
      development of BBNs with improved logical capabilities represent the key to
      improved decision making in pathology.

PMID- 8570285
TI  - Applications of neural networks in histopathology.
AB  - ANN methods are one of several nonparametric approaches to classification. They
      are based on an adaptive, connectionist model of information storage and
      processing and learn by example rather than explicitly programmed classification
      rules. Their greatest strength probably is the ease with which they capture
      nonlinear and interactive feature effects during training, though at a higher
      risk of overtraining then is found with traditional classifiers. ANN can be used
      to process image data, but so far not to classify complex natural images
      directly. Instead, image dimensionality is reduced to a set of extracted features
      for ANN input. ANN finds growing use in time series signal processing and
      radiology. In anatomic pathology, ANN pilot studies are published for tumor
      classification. Pap smear analysis, and chromosome identification. Each
      application requires proper sampling technique, minimising bias in training and
      testing to assure the ANN classifier will perform prospectively as expected. With
      careful arrangement of input features, ANN can be used for prognostic as well as
      diagnostic models.

PMID- 8570286
TI  - Syntactic structure analysis.
AB  - Syntactic structure analysis is a relatively new technique in diagnostic
      quantitative pathology that, based on the graph theory, can provide quantitative
      information on tissue architecture. This article gives an introduction to
      syntactic structure analysis and discusses the potential of syntactic structure
      analysis in diagnostic quantitative pathology. In addition, some examples of its
      application in histo- and cytopathology are presented and it is speculated which
      other applications the user of syntactic structure may find for quantitation of
      architecture in diagnostic quantitative pathology.

PMID- 8570287
TI  - Unbiased stereologic techniques for practical use in diagnostic histopathology.
AB  - Grading of malignancy by the examination of morphologic and cytologic details in
      histologic sections from malignant neoplasms is based exclusively on qualitative
      features, associated with significant subjectivity, and thus rather poor
      reproducibility. The traditional way of malignancy grading may therefore not be
      optimal regarding the scientific and clinical value in selecting specific therapy
      and making prognostic forecast for the individual patient with a solid cancer. A
      lot of examples in the international literature document the urgent need for
      replacing morphologically based techniques by introducing quantitative techniques
      in the histopathologic discipline of malignancy grading. Unbiased stereologic
      methods, especially based on measurements of nuclear three-dimensional mean size,
      have during the last decade proved their value in this regard. In this survey,
      the methods are reviewed regarding the basic technique involved, sampling,
      efficiency, and reproducibility. Various types of cancers, where stereologic
      grading of malignancy has been used, are reviewed and discussed with regard to
      the development of a new objective and reproducible basis for carrying out
      prognosis-related malignancy grading of solid tumors. This new, unbiased attitude
      to malignancy grading is associated with excellent virtues, which ultimately may
      help the clinician in the choice of optimal treatment of the individual patient
      suffering from cancer. Stereologic methods are not solely applicable to the field
      of malignancy grading. Surgical pathologists can use a wide range of these
      techniques in the routine of diagnostic and scientific work. It is not the
      intention, however, to give an extensive review of the methodology, but two other
      techniques will be covered: Unbiased estimation of volume of, and total tumor
      cell number within, solid neoplasms. Three-dimensional tumor size may be of
      relevance in staging cancer, whereas total tumor cell number may be of interest
      in the scientific work with malignancies and treatment of cancer.

PMID- 8570288
TI  - 3D reconstruction and quantitation of pathological tissues.
AB  - 3DR techniques are under continuous development, as is the technology which
      supports them. Systems developed for engineering and other applications are
      coming within the price range of many users. Recently publications have started
      to appear using standard high-quality graphics workstations. As these are coming
      down in price, more applications will be possible. The advent of new computer
      technology, notably possible. The advent of new computer technology, notably
      highly parallel systems and chips such as the Intel i860, offer the prospect of
      very fast reconstructions and the software to make 3DR a routine technique. Most
      significant however is the continuing increase in type and numbers of scanning
      systems, both macroscopic and microscopic. Prior to these systems becoming
      available, the critical limiting factor inhibiting the wide application of 3DR
      was generating adequately registered, undistorted, complete sets of serial
      section data for the reconstruction process. The fact that scanning optical
      microscopes can produce such datasets easily means that the everyday use of 3DR
      for studies of pathology is now feasible.

PMID- 8570289
TI  - Nuclear texture measurements in image cytometry.
AB  - DNA image cytometry is widely used in cytopathology as a means to obtain
      objective information concerning the diagnosis and prognosis of human cancer.
      Using specially designed devices, the high resolution spatial and photometric
      information is available in the images of a microscopic field. If quantitative
      DNA specific stains are used the chromatin distribution in the cell nuclei can be
      measured, which is one of the critical features for cytopathological analysis. In
      normal cells, changes in the chromatin appearance reflect changes in the
      activation patterns of genes. In tumors, dramatic changes in the nuclear
      chromatin appearance are common and have been associated with the progression of
      the disease. Features describing the chromatin distribution pattern are referred
      to as texture features. Nuclear texture features are sensitive to the differences
      between the various descriptive classes of chromatin patterns. In this paper we
      discuss the main categories of nuclear texture measurements. Texture features can
      be roughly divided into the following categories: 1) descriptive statistics of
      chromatin distribution; 2) discrete texture features; 3) range extreme; 4)
      markovian; 5) run length and 6) fractal texture features. Representative features
      of each of the above categories are discussed together with mathematical
      formulas, simple figures for explanation as well as images of typical cells which
      differ significantly in some texture features. Key references are also provided.

PMID- 8570290
TI  - Quantitation in immunohistochemistry. A research method or a diagnostic tool in
      surgical pathology?
AB  - Quantification of immunohistochemical methods is feasible by two ways, namely
      microscope photometry and TV densitometry. The rapid progress of computer
      technology argues largely in favour of the second system. From the
      immunohistochemical methods either ABC, the PAP or the APAAP method should be
      chosen. Diaminobenzidine is the H2-donor of choice for the peroxidase mediated
      systems, whereas Fast Red TR or Neufuchsin can be used with the APAAP system. The
      test efficiency, and the precision of measurements should be investigated in each
      laboratory doing quantitative immunohistochemistry. Low levels of coefficients of
      variation (CV) should be reached for one field of interest. Examples of
      introducing the method of quantitative immunohistochemistry in a routine
      laboratory are discussed. The demonstration of either a steroid receptor or a
      proliferation marker, such as PCNA or Ki67, are seemingly of the greatest
      clinical interest.

PMID- 8570291
TI  - Fractals in pathology: are they really useful?
AB  - Through several examples selected from functional and pathological cells and
      tissues, including surface, cytoplasmic and nuclear membranes one will focus on
      the application of the fractal approach to measuring irregular and complex
      structures, on the importance of evaluating real morphology and on its potential
      role in understanding of tumor biology.

PMID- 8570292
TI  - Organized quantitative pathology. Short review of the activities of the Committee
      for Diagnostic Quantitative Pathology from 1981 to the foundation of the
      International Society of Diagnostic Quantitative Pathology in 1994.
AB  - The Committee for Diagnostic Quantitative Pathology (CDQP), known originally as
      the Committee for Diagnostic Morphometry, ceased to exist under the original
      title and was converted to the International Society for Diagnostic Quantitative
      Pathology (ISDQP) in Amsterdam, September 14, 1994. The history of this society
      started in 1981 in a conference <<Morphometry in Morphological Diagnosis>> held
      at Koli, Finland. Since the original meeting the group of quantitative
      pathologists organized yearly gatherings: Symposia on Diagnostic Quantitative
      Pathology (earlier known as Symposia on Morphometry in Morphological Diagnosis)
      every other year, and meetings in association with the European Society of
      Pathology Congresses in the intervening years. In 1981, the symposium had 23
      participants, in 1994, the International Society for Diagnostic Quantitative
      Pathology had over 300 members from six continents. During the short period of
      its existence the society has witnessed a steadily growing trend in educational
      courses on quantitative pathology. The general policy of the Committee, now
      Society, has willingly supported all activities which can be expected to lead to
      valuable results in quantitative microscopy and associated fields either through
      development of education, methodology or practical applications. By arranging a
      course of Diagnostic Quantitative Pathology the society participates in the
      activities of the European School of Pathology in Torino. The next symposia of
      the Society will be arranged in Heidelberg, October 1995 and in Sendai, Japan,
      October/November 1996.

PMID- 8570293
TI  - Do clocks run clockwise?

PMID- 8570294
TI  - Cost-effective neonatology for the general pediatrician.

PMID- 8570295
TI  - Respiratory distress syndrome for the practicing pediatrician.

PMID- 8570296
TI  - Commonly asked questions regarding infections in neonates.

PMID- 8570297
TI  - Neonatal enteral and parenteral nutrition.

PMID- 8570298
TI  - Assessment of large and small for gestational age newborn infants using growth
      curves.
AB  - Abnormal fetal growth patterns are associated with higher rates of neonatal
      morbidity. Measurement of anthropometric parameters immediately after birth,
      prior to the onset of potential neonatal symptoms, allows the physician to make
      an assessment as to which infants are at high risk. In general, a two-tiered
      approach will allow the physician to make the distinction between high- and low
      risk infants. First, the standard one-factor anthropometrics--weight, length, and
      occipitofrontal head circumference--are plotted on curves that are appropriate
      for the population. In the vast majority of cases, these measurements give enough
      information regarding neonatal risk. When the standard measurements conflict with
      the clinical history or are disproportionate, the use of specialty one-factor
      anthropometrics, and especially two-factor body proportion assessments represent
      the second tier of assessment that can give greater insights into the etiology of
      abnormal fetal growth and can further define the groups at risk for neonatal
      sequelae.

PMID- 8570299
TI  - Blunted peripheral chemoreceptor response to hyperoxia in a group of infants with
      bronchopulmonary dysplasia.
AB  - Infants with BPD often suffer from chronic hypoxia and require supplemental
      oxygen (O2). This might affect the sensitivity of peripheral chemoreceptors.
      Therefore, we assessed peripheral chemoreceptor function in 25 infants with
      bronchopulmonary dysplasia (BPD) of varying severity, using the hyperoxic test.
      These infants were compared with 35 preterm infants who did not develop BPD. All
      infants were tested during the 40th week of postconceptional age and their mean
      postnatal age was 81.5 +/- 16.3 days. Sixty percent (15/25) of the BPD infants
      lacked a hyperoxic response, while the proportion of nonresponders to O2 among
      the other groups was 20% (7/35). The intensity of this response was negatively
      correlated to time spent on a ventilator and positively to time without
      supplemental oxygen. The intensity of chemoreceptor function was closely related
      to the severity of BPD; none of the infants with the most severe form of BPD
      (grade 3) showed a ventilatory response to hyperoxia. Furthermore, infants with
      BPD needed significantly longer time to increase their saturation than did non
      BPD infants (4.7 and 9.3 sec, respectively). We conclude that many infants with
      BPD, particularly those with the most severe form of the disease, have abnormally
      functioning peripheral chemoreceptors.

PMID- 8570300
TI  - The effects of hyperoxia, mechanical ventilation, and dexamethasone on pulmonary
      antioxidant enzyme activity in the newborn piglet.
AB  - It has been previously shown that prophylactic, intravenous dexamethasone (DEX)
      and intratracheal recombinant human Cu/Zn superoxide dismutase (SOD) ameliorate
      lung injury in newborn piglets treated with 48 hr of hyperoxia and mechanical
      ventilation. DEX has many pharmacologic effects, including the possible induction
      of antioxidant enzyme systems. To investigate whether the effects of DEX are
      mediated by an increase in endogenous antioxidant enzyme activity, 5 groups of
      term newborn piglets were studied: Group 1 piglets were ventilated with room air
      for 48 hr; Group 2 animals were ventilated with 100% O2 for 48 hr; Group 3
      animals were ventilated with room air for 48 hr and received DEX (0.7 mg/kg)
      every 12 h; Group 4 were ventilated with 100% O2 for 48 hr and also received DEX;
      Group 5 animals were no ventilated and were sacrificed at time 0. At the
      conclusion of the studies, bronchoalveolar lavage (BAL) was performed and the
      lungs were removed and homogenized. Lung tissue and BAL were analyzed for SOD,
      catalase, GPX activities, and total protein concentration. No significant
      differences in any of these assays were seen in either lung tissue or BAL in the
      5 groups. These observations indicate that 48 hr of hyperoxia, mechanical
      ventilation, or dexamethasone treatment does not induce activity of SOD,
      catalase, or glutathione peroxidase (GPX) in the lungs of newborn piglets. Thus
      postnatal DEX appears to minimize neonatal lung injury by mechanisms that are
      independent of these enzymes.

PMID- 8570301
TI  - Bronchoalveolar lavage studies in children without parenchymal lung disease:
      cellular constituents and protein levels.
AB  - We evaluated bronchoalveolar lavage fluid (BAL) for cellular constituents,
      concentration of total protein (TP), albumin (AL), fibronectin (FN), and
      hyaluronic acid (HA) in 16 children aged 2-32 months without pulmonary
      inflammatory or parenchymal disease to establish reference values. We compared
      our data to those reported in older children and in normal adult volunteers. BAL
      results were obtained simultaneously from the right middle lobe and the lingula.
      Results indicated that children younger than 3 years of age had a higher number
      of cells/mL than older children and adults (59.9 x 10(4) vs. 17.6 x 10(4) and 12
      x 10(4)). Differential cell count revealed that the percentages of alveolar
      macrophages (AM), lymphocytes (LYM), and eosinophils (EOS) were similar to those
      obtained in older children and in adults, whereas the percentage of neutrophils
      (NEU) was higher in younger children (NEU 5.5 vs 1.6 and 1.2%, respectively) than
      in older children and adults. The latter difference was even greater in infants
      under 12 months of age (NEU 7.6%). The concentrations of TP, AL, FN, and HA in
      children's BAL samples were compared to values reported for adults. There were no
      differences between infants and children 13-32 months of age or normal adults.
      BAL fluid obtained simultaneously from the middle lobe and lingula were not
      significantly different. In conclusion, this is the first report on BAL values
      (cellular and noncellular constituents) in children younger than 3 years. The
      results may be used as reference values for further studies in children with
      parenchymal lung disease in this age group.

PMID- 8570302
TI  - A critical assessment of uncalibrated respiratory inductance plethysmography
      (Respitrace) for the measurement of tidal breathing parameters in newborns and
      infants.
AB  - We have compared results obtained with an uncalibrated respiratory inductance
      plethysmograph (RIP) with those of a face mask and pneumotachograph (PNT) for the
      computerized measurement of the time to reach peak tidal expiratory flow as a
      ratio of total expiratory time (tPTEF:tE). Simultaneous measurements were made in
      32 healthy neonates aged 0-3 weeks, 35 healthy infants aged 5-82 weeks, and 28
      infants aged 15-94 weeks with physician diagnosed recurrent wheeze. The group
      mean (+/- SD) values of tPTEF:TE determined using a PNT were 0.455 (+/- 0.129),
      0.263 (+/- 0.077), and 0.232 (+/- 0.089) for the neonates, healthy infants and
      infants with recurrent wheeze respectively. RIP gave mean (+/- SD) values that
      were 0.055 (+/- 0.044) and 0.025 (+/- 0.104) lower than the PNT in healthy
      neonates and infants with recurrent wheeze respectively; RIP values were 0.002
      (+/- 0.073) higher in the healthy infants over 4 weeks of age than measurements
      by PNT. Although the difference between the two measurements was not related to
      the thoracoabdominal phase angle, as measured from Lissajous figures, examination
      of the RIP ribcage and abdominal signals revealed that many healthy subjects,
      while appearing clinically in phase, had ribcage and abdominal signals that
      differed markedly from each other in terms of convexity/concavity during early
      expiration. This may explain the lack of agreement between the two methods. We
      conclude that uncalibrated RIP should be used with caution for the determination
      of tPTEF:tE, even in subjects whose ribcage and abdomen appear to move
      synchronously. The measurement of tPTEF:tE did not differentiate between the
      healthy infants and infants with recurrent wheezing.

PMID- 8570303
TI  - Effectiveness of chloroquine therapy in idiopathic pulmonary hemosiderosis.

PMID- 8570304
TI  - The relationship between infection and inflammation in the early stages of lung
      disease from cystic fibrosis.
AB  - We examined the relationship of pulmonary infection and inflammation in cystic
      fibrosis (CF) by performing 31 bronchoalveolar lavages (BAL) in 14 young children
      with minimal lung disease from CF. While 10 of the 14 patients had elevated
      polymorphonuclear leukocyte (PMN) counts initially, only 4 had bacteria generally
      regarded as pathogenic in the recovered BAL fluid. Three of these 4 and 6 of the
      others had follow-up bronchoscopies at 6 months intervals. PMN counts remained
      normal for only one patient. However, pathogenic bacteria were recovered during
      the repeat BALs only in those patients who were colonized initially.
      Proinflammatory cytokines and proteinases were generally elevated, and
      interleukin-8 (IL-8) concentration correlated inversely with oxygen saturation
      (SaO2). No complications of the procedure occurred. We conclude that BAL
      identifies inflammation and the presence of bacteria in the lower airway at an
      early stage of the disease. This information may be used to guide therapy in
      patients too young or otherwise unable to produce sputum. These data also suggest
      that inflammation is present early in the course of CF lung disease before
      colonization and infection of the lungs with potentially pathogenic bacteria
      occurs. Since inflammation appears to be the earliest detectable evidence of lung
      disease in CF, monitoring of inflammation with BAL may serve as a useful marker
      of clinical benefits from new treatments in patients with minimal lung disease.

PMID- 8570305
TI  - High levels of complement-activation capacity in sera from patients with cystic
      fibrosis correlate with high levels of IgG3 antibodies to Pseudomonas aeruginosa
      antigens and poor lung function.
AB  - Heat-stable opsonins from sera of cystic fibrosis (CF) patients were investigated
      for their ability to activate complement. Complement activation by Pseudomonas
      aeruginosa after opsonization with patient serum was examined in a complement
      consumption assay. Absorption of patients' sera with formalin-treated and boiled
      bacteria removed specific antibodies and the complement activation decreased. We
      found a positive correlation between serum complement-activation ability and IgG3
      antibody levels to lipopolysaccharide (LPS), alginate, and a crude mixture of P.
      aeruginosa antigens (sonicate) in a group of patients with high levels of anti
      Pseudomonas precipitins. In the same group of patients a significant negative
      correlation was found between complement activation and lung function. Eighteen
      patients have been followed longitudinally with serum samples covering the pre
      infection, the early, and the late stages of chronic infection. Patients with
      poor lung function showed significantly higher levels of complement-activation
      capacity. We conclude that patients with high levels of specific IgG3 antibodies
      are able to induce a high level of complement activation and then develop more
      aggressive pulmonary tissue damage, probably secondary to local immune complex
      formation.

PMID- 8570306
TI  - Effects of combined treatment with rhDNase and airflow oscillations on
      spinnability of cystic fibrosis sputum in vitro.
AB  - Treatment with either rhDNase or high-frequency oscillation has been shown to be
      effective in improving the physical and transport properties of airway secretions
      in cystic fibrosis (CF). The objects of this in vitro study was to examine
      whether combined treatment with oscillation and rhDNase results in greater change
      of CF sputum spinnability than either treatment by itself. Aliquots of sputum
      (0.4 g) from eight CF patients were subjected to the following protocols for 15
      minutes and then followed for a total of 30 minutes: 1) incubation with 0.04 ml
      DNase 50 micrograms rhDNase/normal saline (10% dilution) at 37 degrees C to
      achieve 5 micrograms DNase/g of sputum final concentration; 2) airflow
      oscillation at 27 Hz similar to the airflow magnitude produced by a commercial
      high-frequency chest compression (HFCC) device; 3) negative control with no
      treatment; 4) positive (dilution) control, incubating with 10% saline by volume;
      5) combination of DNase and oscillation, and 6) combination of saline and
      oscillation. For each protocol, sputum spinnability (in mm, mean +/- SD) was
      measured by means of a filancemeter at baseline, 15, and 30 minutes. Treatment
      with DNase decreased spinnability significantly more than either saline or
      oscillation at 15 and 30 minutes (P < 0.02 and P < 0.04, respectively).
      Incubation with saline or oscillation of CF sputum for 15 and 30 minutes
      decreased spinnability significantly compared with control. The combination of
      DNase and oscillation decreased spinnability significantly more than treatment
      with DNase alone (3.74 +/- 0.45 vs. 6.54 +/- 0.73 at 15 minutes, P <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570308
TI  - Congenital central hypoventilation syndrome: cardiorespiratory responses to
      moderate exercise, simulating daily activity.
AB  - Children with congenital central hypoventilation syndrome (CCHS) lack normal
      awake ventilatory responses to hypoxia and hypercarbia, yet engage in daily
      activities typical of similarly aged children. Our patients with CCHS are
      assessed annually with a walking treadmill protocol to assess physiologic
      responses to different levels of simulated daily activity. We hypothesized that
      children with CCHS (compared with age- and sex-matched healthy controls) would 1)
      exercise for shorter durations and reach lower peak speed and incline on the
      treadmill; 2) become more hypoxemic, more hypercarbic, and develop less
      tachycardia during activity; and 3) take longer to return to baseline
      oxygenation, ventilation, and heart rate than normal children. Seven children
      with CCHS [mean age, 6.9 +/- 3.0 (SD) years] who required 24 h/day ventilatory
      support (diaphragm pacers while awake and mechanical ventilation asleep) and 7
      controls performed a walking protocol on a treadmill with progressive increments
      in speed and incline. Hemoglobin saturations (SaO2), end-tidal carbon dioxide
      concentrations (ETCO2), and heart rates (HR) were recorded at baseline
      conditions, during activity and during recovery. There were no significant
      differences between children with CCHS and controls in baseline values, duration
      of activity, peak speed, and incline achieved during walking and recovery time to
      baseline once the treadmill had stopped. However, children with CCHS became
      significantly more hypoxemic and hypercarbic during activity (P < 0.05), and they
      had a lower percent increase in HR during treadmill walking than controls (P <
      0.05). These results offer the clinician an opportunity to adjust clinical
      management in children with CCHS by providing specific recommendations to parents
      about appropriate levels of activity for their children with CCHS.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8570307
TI  - Staphylococcal pneumonia in childhood: will early surgical intervention lower
      mortality?
AB  - Staphylococcus aureus pneumonia (SAP) continues to be a serious bacterial
      infection which is associated with a high incidence of complications. We
      retrospectively reviewed the case records of 36 infants and children admitted
      with SAP to the Sophia Children's Hospital between 1970 and 1992 to analyse
      changes over time in the clinical presentation, diagnostic work-up, management
      and complications. Fifteen of these 36 children (42%) were less than 1 year old.
      Fever (97%) and respiratory distress (83%) were the most common symptoms at the
      initial presentation. Chest X-ray findings on admission or during hospitalisation
      included pleural effusion (75%), pneumothorax (47%), and abscess and/or
      pneumatocele (39%). Diagnostic and/or therapeutic thoracentesis of pleural fluid
      was performed in 17 of the 36 patients (47%). Twenty-one patients (58%) needed
      chest tube drainage. Twelve had a thoracotomy (33%). Artificial ventilation was
      needed in 13 of the patients (36%). Extrapulmonary complications included
      convulsions in 6 patients (17%) and osteomyelitis in 2 children (6%). The mean
      duration of hospitalization was 36 days. Two of the 36 children died (6%). The
      low mortality rate in this study may be the result of the relatively high rate of
      thoracotomy and of improvements in supportive treatment.

PMID- 8570309
TI  - Carotid bodies and ventilatory response to hypoxia in aminophylline-treated
      piglets.
AB  - Peripheral chemoreceptors may be immature in neonatal animals, exhibiting
      maturational changes in the perinatal period. Even though methylxanthines are
      respiratory stimulants, many premature neonates do not respond to them. Thus, we
      hypothesized that carotid body activity is necessary for aminophylline to reverse
      hypoxia-induced respiratory depression. We exposed 16 anesthetized newborn
      piglets (age 2-7 days) to hypoxia (inhalation of 12% oxygen) for 5 min.
      Aminophylline (15 mg/kg iv) was administered either prior to (11 piglets) or
      following (5 piglets) carotid body denervation (CBD). Before CBD, hypoxia
      elicited transient initial increases in tidal volume (from 79 +/- 4 to 99 +/- 1%
      of maximum, mean +/- SE), minute ventilation (from 64 +/- 5 to 93 +/- 4%), and
      peak phrenic electroneurogram (from 63 +/- 8 to 91 +/- 6%, all P < 0.05). This
      was followed by a decrease in tidal volume, minute ventilation and phrenic
      electroneurogram (all P < 0.05). Prior to CBD, aminophylline pretreatment
      prevented the decrease in all the measures of respiratory output during late
      hypoxia. After CBD, hypoxia induced an initial and sustained depression of
      ventilation (tidal volume from 100 to 33 +/- 14%; frequency from 94 +/- 4 to 42
      +/- 17%; minute ventilation from 100 to 32 +/- 14%, all P < 0.05) and phrenic
      electroneurogram (peak phrenic from 100 to 47 +/- 18%; minute phrenic from 85 +/-
      6 to 55 +/- 21%, both P < 0.05). Administration of aminophylline after CBD did
      not prevent the profound respiratory depression elicited by hypoxia in the
      chemodenervated piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570310
TI  - Gadolinium-enhanced MR imaging demonstrates abduction-caused hip ischemia and its
      reversal in piglets.
AB  - Purpose. To determine whether gadolinium-enhanced MR imaging can detect early
      reversible ischemia of the capital femoral epiphysis and physis induced by hip
      hyperabduction in piglets. Materials and methods. Thirteen 1- to 3-week-old
      piglets were placed in maximal abduction of both hips and studied with dynamic
      gadolinium-enhanced MR imaging 1-6 h later to assess ischemia of the 26 femoral
      heads. They were then allowed to ambulate freely for 1 or 7 days, and reimaged in
      neutral position to assess reperfusion. Enhancement was evaluated on MR images
      and compared with histologic findings.Results. Ischemia after hyperabduction
      developed in all 26 cartilaginous epiphyses and in 85 % of the physes. The most
      frequent abnormality was a sharply marginated nonenhancing area in the anterior
      part of the femoral head. A smaller area of ischemia developed in the posterior
      part of the femoral head, adjacent to the acetabular rim. The secondary center of
      ossification was ischemic in 56 % of the hips after 1 h of abduction and in all
      hips after 4 or 6 h (p = 0.02). The overall severity of ischemia was greater with
      increasing abduction time (p < 0.001) and increasing degree of abduction (p <
      0.01). There was partial reperfusion in 83 % of the hips after 1 day of
      ambulation and complete reperfusion in all 26 hips (100 %) after 1
      week.Conclusion. Enhanced MRI detects early ischemia of the epiphyseal and
      physeal cartilage and the epiphyseal marrow. In piglets, ischemia due to
      hyperabduction is reversible if corrected within 6 h.

PMID- 8570311
TI  - MRI "road-map" of normal age-related bone marrow. I. Cranial bone and spine.
AB  - We retrospectively reviewed 733 cranial and 250 spinal T1-weighted MR images of
      patients younger than 24 years to evaluate the bone marrow changes. The signal
      intensity of the bone marrow on short-TR/TE images was compared with that of fat
      and normal muscles in the contiguous region and graded. The signal intensity of
      all anatomic segments was as low as that of muscle, or inferior, in all patients
      younger than 3 months because of hematopoietic tissue and probably greater
      amounts of trabecular bone. The first anatomic segments of cranial bone to become
      hyperintense were the zygomatic bone and mandibular symphysis, followed by the
      presphenoid bone, basisphenoid, basiocciput, calvaria, and the petrous apex.
      After 3 years of age, most patients demonstrated pneumatization of the sphenoid
      sinus. We describe the most interesting changes in the developing spine, which
      occur in the first 2 years of life. The morphology of the vertebral bodies was
      evaluated. The variability of the signal and the morphology of the disks were
      also evaluated. Regional patterns of bone marrow signal intensity and age-related
      differences should not be misinterpreted as a pathologic condition.

PMID- 8570312
TI  - MRI "road-map" of normal age-related bone marrow. II. Thorax, pelvis and
      extremities.
AB  - We retrospectively reviewed T1-weighted MR images of 381 patients aged from 7
      days to 24 years to evaluate the bone marrow change in thoracic wall and
      shoulder, pelvis and proximal femur and upper and lower extremities. The patients
      included in the study were without history of bone marrow disease. A grade of
      from 1 to 4 was assigned to the marrow signal intensity of the examined anatomic
      segments. The signal intensity of all anatomic segments was as low as or lower
      than that of muscle in all patients younger than 2 months, reflecting underlying
      hematopoietic marrow. The first segments to become hyperintense were the
      epiphyseal/round bone ossification centers, followed by the phalanges, diaphysis,
      flat bones and metaphysis. Marrow signal intensity increased in all regions with
      age. While in the epiphysis, round bones and diaphysis bone marrow shows a
      diffuse and homogeneous increased signal intensity with age, in the sternum,
      ribs, scapulae, posterior ilium and metaphysis varying percentages of
      intermediate signal intensity are maintained. An orderly progression of red to
      yellow marrow was established.

PMID- 8570313
TI  - MRI marrow observations in thalassemia: the effects of the primary disease,
      transfusional therapy, and chelation.
AB  - The magnetic resonance bone marrow patterns in thalassemia were evaluated to
      determine changes produced by transfusion and chelation therapy. Thirteen
      patients had T1- and T2-weighted images of the spine, pelvis and femurs. Three
      received no therapy (age range 2.5-3 years). Three were hypertransfused
      (transfused to maintain a hemoglobin greater than 10 g/dl) and not chelated
      because of age (age range 6 months-8 years). Seven were hypertransfused and
      chelated (age range 12-35 years). Signal characteristics of marrow were compared
      with those of surrounding muscle and fat. Fatty marrow (isointense with
      subcutaneous fat) was compared with red marrow (hypointense to fat and slightly
      hyperintense to muscle). Marrow hypointense to muscle was identified as iron
      deposition within red marrow. The untreated group demonstrated signal consistent
      with red marrow throughout the central and peripheral skeleton. Hypertransfused
      but not chelated patients demonstrated marked iron deposition in the central and
      peripheral skeleton. Hypertransfused and chelated patients demonstrated iron
      deposition in the central skeleton and a mixed appearance of marrow in the
      peripheral skeleton. The MR appearance of marrow in thalassemia is a reflection
      of the patient s transfusion and chelation therapy. Iron deposition occurs
      despite chelation therapy in sites of active red marrow. As red marrow retreats
      centrally with age, so does the pattern of iron deposition. The long-term
      biological effects of this iron deposition are unknown.

PMID- 8570314
TI  - MR marrow signs of iron overload in transfusion-dependent patients with sickle
      cell disease.
AB  - Magnetic resonance (MR) marrow signal in the axial and appendicular skeleton of
      13 transfusion-dependent and chelated pediatric patients with sickle cell anemia
      (SSD) was compared with marrow signal in six non-transfusion-dependent patients
      with SSD. Hepatic, pancreatic, and renal MR signal were also evaluated.
      Indication for hypertransfusion therapy was primarily prior history of stroke.
      Transfusion-dependent patients had evidence of iron deposition throughout the
      imaged marrow and the liver, despite deferoxamine chelation therapy. Non
      transfusion-dependent patients did not demonstrate grossly apparent signs of iron
      overload. Red marrow restoration was present in the spine, pelvis, and long bones
      and, in some patients, within the epiphyses. Marrow edema secondary to vaso
      occlusive crises was evident in the metaphyses and diaphyses of long bones in
      areas of both red and fatty marrow and was best seen using fat-saturated T2
      weighted imaging techniques.

PMID- 8570316
TI  - Radiographic patterns and viral studies in childhood pneumonia at various ages.
AB  - We aimed at evaluating the relationship between microbial etiology and chest
      radiograph appearance in various types of pneumonia. In a prospective study, the
      radiographic findings in 479 cases of acute pneumonia in children were compared
      with viral etiology and growth of potential bacterial pathogens in nasopharyngeal
      secretion. As the basis for viral etiology was most conclusive, the material was
      here classified according to the viral findings. The patients were divided into
      three age groups: 0-2, 3-5 and 6-15 years. The chest radiograms were analyzed
      blindly for the presence of hyperinflation and interstitial, alveolar and mixed
      interstitial-alveolar infiltrates. There was a statistically significant
      relationship between low age and occurrence of hyperinflation and interstitial
      infiltrates, and between high age and alveolar infiltrates. No unequivocal
      relationship was found between type of infiltrates or presence of atelectasis and
      proven viral etiology. We conclude that chest radiographs are not a useful
      indicator of microbial etiology in childhood pneumonia.

PMID- 8570317
TI  - A radiologic update on medical diseases of the newborn chest.
AB  - This paper reviews the common spectrum of medical diseases of the neonatal chest.
      Emphasis is on radiographic changes that have been produced by the introduction
      of new therapeutic maneuvers, particularly the use of artificial surfactant in
      treating hyaline membrane disease and the survival of profoundly premature
      newborns (less than 650 g). A discussion of meconium aspiration syndrome,
      neonatal pneumonia, transient tachypnea of the newborn, congenital
      lymphangiectasia, and congenital heart disease is also included. The effects on
      the neonatal chest radiograph of extracorporeal membrane oxygenation and high
      frequency ventilation are also mentioned.

PMID- 8570318
TI  - Rationing ventilatory support for the newborn with respiratory distress.

PMID- 8570315
TI  - Tuberculosis: the resurgence of our most lethal infectious disease--a review.

PMID- 8570319
TI  - Respiratory distress syndrome: therapeutic aspects.

PMID- 8570320
TI  - Sonographically guided cannula positioning for extracorporeal membrane
      oxygenation.
AB  - Drainage problems due to catheter malpositioning are acutely life-threatening in
      patients undergoing extracorporeal membrane oxygenation. In order to reduce these
      complications we introduced sonographically guided catheter positioning. We
      compare the outcome in a group of patients with blind cannula positioning to that
      in a group with sonographically guided catheter positioning. Our results show
      that neonates and young infants especially are at high risk of drainage problems
      due to catheter malposition and that their outcome could be markedly improved by
      introducing sonographically guided cannula insertion.

PMID- 8570321
TI  - Lobar emphysema associated with respiratory syncytial virus pneumonia.
AB  - The etiology of infantile lobar emphysema is frequently unknown; however, partial
      airway obstruction is most often implicated. Although infection and lobar
      emphysema have been linked previously, their cause-and-effect relationship is
      unclear. We present the clinical, radiographic, and pathologic findings in a 9
      day-old infant with acute bronchiolitis due to respiratory syncytial virus (RSV)
      and a clinical and radiographic appearance suggestive of lobar emphysema.
      Pathologically, there was diffuse papillary overgrowth of the bronchiolar
      epithelium due to RSV infection which produced narrowing of the affected airways
      and alveolar overinflation. We speculate that in this instance RSV infection was
      at least associated with the development, and was perhaps the direct cause of
      lobar emphysema.

PMID- 8570322
TI  - Congenital bilobar emphysema.
AB  - Two cases of congenital bilobar emphysema are presented, both of which caused
      neonatal respiratory embarrassment. Plain radiography and lung scintigraphy
      revealed bilobar involvement in one child prior to surgery, while the bilobar
      involvement in the other child was found during a follow-up study.

PMID- 8570323
TI  - Shoe, scimitar or sequestration: a shifting spectrum.
AB  - Congenital abnormalities of the tracheobronchial tree are rare causes of
      recurrent chest infections in childhood. A case is described which shows some
      typical features of horseshoe lung. More detailed imaging revealed complete
      separation of the right and left pleural cavities and the malformation represents
      part of the sequestration spectrum. The case emphasises the need for careful
      evaluation of the pulmonary arteries, veins, bronchi and oesophagus, particularly
      prior to surgery.

PMID- 8570324
TI  - Evaluation of pectus excavatum with repeated CT scans.
AB  - The use of a single CT scan to evaluate the severity of pectus excavatum has been
      popular since its inception. However, there is no objective data to address the
      evolution of the deformity. Using repeated CT scans taken an average of 1 year
      and 3 months apart, eight children with pectus excavatum were prospectively
      followed. The initial pectus indices ranged from 3.6 to 6.8 (mean 5.4 +/- 1.3)
      and the follow-up indices, from 3.5 to 6.7 (mean 5.3 +/- 1.0). No progress of
      pectus excavatum was found during the study period. Our routine five axial chest
      CT sections also helped to specify a pectus index based on the central section
      taken through the deepest part of the deformity, and provided useful information
      for further conservative or surgical management.

PMID- 8570325
TI  - The foundation and early meetings of The Society for Pediatric Radiology.

PMID- 8570326
TI  - Can we judge the strength of a drink?
AB  - Using the method of direct magnitude estimation, ten subjects each judged by
      taste the strength of ten rum/water mixtures; these ranged from 10% to 100% rum.
      Mean judgements of the concentration of rum were highly accurate (r = .99) and
      showed no tendency towards underestimation or overestimation at any
      concentration.

PMID- 8570327
TI  - Simulations of stuttered speech: numbers and types of dysfluencies.
AB  - The purpose of this study was to assess whether stuttered speech could be
      simulated by normal-speaking individuals and to identify significant parameters
      used in the simulation process. The subjects were 24 normal-speaking graduate
      students in speech-language pathology. The subjects were assigned the task of
      simulating stuttered speech given specific levels of severity. Then they were
      asked to listen to the simulated samples and identify the number and types of
      dysfluencies presented. Analysis showed agreement among subjects on the number of
      dysfluencies, with the exception of samples simulating severe stuttering
      behavior. Judging the number of dysfluencies in the simulated samples of severe
      stuttering appeared to be a more difficult task. The types of dysfluencies noted
      by the listeners were restricted primarily to repetitions and prolongations.
      Simulated stuttered speech was therefore judged to be composed of fewer types of
      stuttering behavior than actual stuttered speech is reported to be.

PMID- 8570328
TI  - A cross-sectional analysis of WAIS-R aging patterns with psychiatric inpatients:
      support for Horn's hypothesis that fluid cognitive abilities decline.
AB  - WAIS-R aging patterns were examined for a group of 200 psychiatric inpatients.
      Inpatients were grouped into six age categories: less than 24, 24-28, 29-32, 33
      38, 39-43, and greater than 43 years. Verbal and Performance sums of scaled
      score, subtest scaled score, and raw score total, and individual item score means
      were examined for each age category. The classical aging pattern was observed
      wherein more crystallized cognitive abilities remained stable over age groups of
      the life span while more fluid abilities dropped sharply with their increasing
      ages. Results supported the decline in fluid cognitive abilities hypothesis for
      WAIS-R aging patterns advocated by Horn in 1985 and Kaufman in 1990.

PMID- 8570329
TI  - From behavioral chronobiology to chronopsychology with special reference to
      circadian fluctuations of emotionality.

PMID- 8570330
TI  - Simple indicators of physical working capacity.
AB  - Traditional methods used to estimate an individual's physical working capacity
      have at least one disadvantage in common, namely, the demand for expensive
      equipment such as cycle ergometers or treadmills. Consequently, the search for
      suitable tests performed in the field has been extensive. Most field tests do,
      however, require a maximal performance from the subject. The present
      investigation compared two special field tests, walking and running, both of a
      submaximal character, with (a) a treadmill run test and (b) a standardized cycle
      ergometer test. The comparisons were made to judge whether these field tests have
      the potential to replace or complement laboratory tests in certain situations,
      for example, when the purpose is to monitor training progress over time.
      Correlations were generally high and statistically significant within as well as
      between tests. Higher values were observed between field running and the
      laboratory tests than with field walking. This was true especially for the higher
      reference levels. Despite this, field walking may still be the best alternative
      for elderly persons or subjects recovering from injury, since the results
      indicate that walking, when performed intensely enough, gives a fairly good
      estimate of an individual's physical working capacity.

PMID- 8570331
TI  - Bibliographical note on behavioral aspects: on the margin of the 50th anniversary
      of the Minnesota Starvation-Nutritional Rehabilitation experiment.
AB  - The principal technical aim of this note is to bring together bibliographic
      information on the papers dealing with the behavioral aspects of the study and
      published both before and, in particular, after the appearance in print of the
      two-volume treatise on The Biology of Human Starvation by Keys, et al. in 1950,
      which provides a systematic, comprehensive account. The communications fall into
      three categories: methods, results, and overviews. The section on results is
      concerned primarily with the effects on personality.

PMID- 8570332
TI  - Chronic pain is associated with deficits in information processing.
AB  - Beginning with the theoretical premise that pain stimuli are liable to perturb
      the ordinary dynamical state of the brain, we hypothesized that individuals in
      pain may experience impaired information processing. A sample of 19 persons
      complaining of chronic pain and a comparison sample of 25 persons having
      sustained head trauma were obtained by retrospective chart review. The chronic
      pain group consisted of 19 persons whose primary complaint was significant
      chronic pain, with no known history of head trauma or neurologic disorder. The
      comparison group consisted of 25 persons who had sustained mild to moderate head
      traumas. All subjects were administered information processing and motor subtests
      of the Human Performance Measurement System, a computerized set of measures. Both
      groups obtained mean z scores below the normative mean on all measures except
      visual digit span. There were no differences between groups on motor measures,
      visual digit span, and visual-spatial memory. On 2 of 6 information-processing
      tests, pain patients performed more poorly than head-trauma patients. The results
      suggest that pain may disrupt cognitive performances which depend on intact speed
      and capacity of information processing.

PMID- 8570333
TI  - Stress experienced while travelling without sight.
AB  - The purpose of this study was to examine the stress reaction of pedestrians
      travelling without sight and the stress-reducing effect of a relaxation exercise
      immediately following travel. 16 students in special education volunteered for
      this experiment. They were blindfolded while travelling. A trait-state-anxiety
      questionnaire was administered. Analysis of variance indicated statistically
      significant effects. Travelling without sight increased state-anxiety as compared
      to trait-anxiety. With a simple relaxation technique, state-anxiety was reduced
      appreciably.

PMID- 8570334
TI  - Deterioration of the high-mounted brake light.
AB  - An unusually high failure rate in the high-mounted, center brake light was
      observed in a survey of normal local traffic. Such failure increases the
      potential for delay or error in perception of the rear lights by following
      drivers.

PMID- 8570335
TI  - Styles of regulation in the bipolar spectrum.
AB  - Styles of regulation were assessed with the Serial Color-Word Test in a group of
      35 compensated DSM-III--R bipolar patients (Bipolar) and in 3 control groups:
      Major Depression (n = 35), Schizophrenia (n = 50), and self-rated Personality
      Disorder (n = 40). On several measures of nonlinear change (V), patients in the
      Bipolar group had mean scores between those of the Personality Disorder and the
      Schizophrenic groups, and overlapped with those of the Major Depression group.
      Patients in the Bipolar group with clearcut temperaments (hyperthymic or
      depressive) were significantly more dissociative and less stabilized than other
      patients in the same group. A further group of nonclinical subjects with
      hyperthymic temperament (n = 20) was significantly more dissociative than the
      Personality Disorder group.

PMID- 8570336
TI  - Relationship between heart rate and preference for tempo of music.
AB  - People prefer music with tempi ranging from 70 to 100 cycles per minute similar
      to that of adults' heart rate within normal daily situations. Previous studies of
      the relation between preferred tempi and heart rates using a pure tone also have
      indicated that subjects tended to prefer tempi similar to their heart rates. The
      present study examined this relationship using a musical piece (the theme of
      "It's a small world") as a stimulus. 14 undergraduate women were subjects who
      searched for their favorite tempi by controlling the musical tempo by themselves.
      The most preferred tempo was close to their cycle of heart beats, however, tempi
      that were one and a half and twice as fast as the heart rate were less preferred
      in the present study than in a previous study using a tone. Subjects preferred
      faster tempi in the descending series of stimuli than in the ascending one, and
      hence were influenced by the initial value of the tempo in the trial sequence.
      The effects due to the differences of the meaning of the stimuli are considered.

PMID- 8570337
TI  - Frontal N30 potential following a sustained voluntary movement.
AB  - With 6 male subjects we investigated whether the decreased amplitude in the
      frontal N30 potential of Somatosensory Evoked Potentials is related to a
      sustained voluntary movement or not. We concluded that the diminution of frontal
      N30 was also closely related to the sustained voluntary movement.

PMID- 8570338
TI  - Dialog organization and functional communication in a medical assistance task by
      phone.
AB  - This study is based on a corpus of 110 dialogs recorded in a medical assistance
      telephonist's workstation. Given the nature of the task, we have considered five
      main variables in dialog (topics) as well as their order of occurrence
      (sequences). These data were analyzed with a lexical analysis program. Results
      show a great difference between Operator/Specialist dialog and
      Operator/Nonspecialist dialog. Dialog "script" is very strong in the first case
      in which the operator merely plays a feedback role (routine procedures). If the
      caller is a private individual, the situation is often an indefinite problem, and
      the operator may have to adapt to the person (weak script) to obtain relevant
      information as quickly as possible (problem-solving procedures). This provides
      confirmation of the operator's twofold competence (efficient decision-making,
      dialog management).

PMID- 8570339
TI  - The ecology of alcohol consumption.

PMID- 8570341
TI  - Season of birth and handedness revisited.
AB  - In a sample of 15,390 students, no significant difference in the season of birth
      could be found between right- and left-handers, classified according to their
      responses to the Edinburgh Handedness Inventory. A separate analysis for each sex
      also yielded nonsignificant differences.

PMID- 8570340
TI  - Man's triune conscious mind: Part III.
AB  - The perceptual model, discussed previously in Part II, is applied to the
      organization of the visual cortex in a search for "consciousness neurons," i.e.,
      sources of sensations, images, and percepts. It is hypothesized that these three
      conscious phenomena emerge in the primary visual cortex, Area V1, possibly from
      neurons in its Layer 4.

PMID- 8570342
TI  - Theoretical extrapolations in "temporal delays in incorporation of events into
      dreams".
AB  - In 1995 Powell, et al. presented fascinating information about the temporal
      vicissitudes in the incorporation of waking experiences into dream content. While
      they correctly pointed out the major methodological flaw in their study, they
      neglected major theoretical difficulties, especially in extrapolating to rat
      neural mechanisms.

PMID- 8570343
TI  - Underestimation of sensorimotor task-induced blood-pressure changes by posttask
      sphygmomanometry.
AB  - For assessment of cardiovascular effects of sensorimotor work, blood pressure is
      commonly measured by arm sphygmomanometry. A technique introduced by Penaz makes
      it feasible to monitor blood pressure noninvasively and continuously from the
      finger artery which measures give high correlations with intraarterial
      measurement. This study compared blood-pressure changes induced by a standard
      sensorimotor task using sphygmomanometry and the Penaz-method. It was
      investigated whether sphygmomanometrically recorded blood pressure can be used to
      estimate task-induced blood-pressure changes and whether inflating the cuff to
      different maximum pressures induces blood-pressure changes. 46 normotensive
      individuals were randomly assigned to the discomfort group (maximum arm-cuff
      pressure of 280 mmHg) or to the control group (maximum arm-cuff pressure of 160
      mmHg). The experiment consisted of six tasks of 4 min. each. Results indicated
      that sphygmomanometries under-estimated task-induced blood-pressure changes and
      that phasic systolic and diastolic blood-pressure elevations during the task were
      leveled off shortly after the end of the task. Effects of 'cuff-inflation
      hypertension' were not found. The Penaz-method appears to be more appropriate
      than sphygmomanometry if dynamic aspects of blood pressure are of interest.

PMID- 8570344
TI  - Problems in left-right discrimination in a high-IQ population.
AB  - The prevalence of difficulties in left-right discrimination was investigated in a
      group of 2,720 adult members of the high-IQ societies Mensa and Intertel. Over
      all, 7.2% of the men and 18.8% of the women evaluated their left-right
      directional sense as poor or below average. Participants who were relatively
      ambidextrous experienced problems more frequently than did those who were more
      strongly left- or right-handed. Age differences were also evident, with
      participants age 17-29 reporting the highest rate of problems, and participants
      age 60 and over reporting markedly lower rates than those age 30-59. The observed
      patterns of gender differences were maintained within these age- and strength-of
      handedness subdivisions. The basis for selecting the items that form the
      handedness inventory used is discussed.

PMID- 8570345
TI  - Comparison of two methods for scoring syntactic complexity.
AB  - Summary scores for Developmental Sentence Scoring and the Index of Productive
      Syntax were obtained from the language samples of 29 preterm children at
      preschool age. A moderate correlation obtained between these two measures of
      syntactic complexity. Only Index of Productive Syntax scores distinguished the
      language abilities of 19 neurologically normal from 10 suspect children.

PMID- 8570346
TI  - Stress, coping, and injuries in male and female high school basketball players.
AB  - Past research has identified a positive relationship between life-event stress
      and football injuries, but research in other sports has yielded more ambiguous
      results. It seems, then, that the relation of life stress and injury may be sport
      specific and that different sports must be studied separately before such a
      relationship is assumed. The present investigation examined the relationships
      among life-event stress, coping skills, social support, and injuries of male and
      female high school basketball players. Contrary to the hypothesis, the number of
      days missed due to injury was not significantly related to life-event stress. As
      expected, the injury measure was negatively correlated with both the coping
      skills and social-support variables, but these correlations did not reach
      statistical significance. Recommendations for research are discussed.

PMID- 8570347
TI  - Listeners' reactions to misarticulation: a methodological investigation.
AB  - It has been shown that listeners react negatively to speakers with abnormal
      articulation. There is no evidence indicating whether the actual placement of the
      occurrence of a misarticulation in a passage influences listeners' reactions.
      Subjects in this study heard a 98-word recording of a speaker feigning a
      misarticulation of /1/. One group of 20 subjects heard the misarticulation within
      the first five words of the recording. A second group heard the misarticulation
      within the first five words of the recording. All subjects rated the speaker on
      13 bipolar scales, representing three dimensions of judgment. Findings indicate
      that the recorded samples were not rated differently. This placement of the token
      error did not influence subjects' judgments of the speaker.

PMID- 8570348
TI  - Relation between reaction time and the phase of spontaneous and controlled
      breathing patterns.
AB  - In this study simple reaction time (simple RT) to a visual stimulus of a single
      subject was measured during spontaneous and controlled breathing, in which the
      duration of expiration was prolonged (Asian technique). The phases of breathing
      were classified as the pause between expiration and inspiration, the inspiration
      phase, the transition from inspiration to expiration, and the expiration phase.
      Analysis of data from about 6000 trials indicated that RT to the stimulus was
      shortest during the transition from inspiration to expiration in controlled
      breathing.

PMID- 8570349
TI  - Blue questionnaires and blue mood.

PMID- 8570350
TI  - A preliminary analysis of the coordination of reaching, grasping, and walking.
AB  - The purpose of this investigation was to describe the strategies used by
      individuals when motor systems controlling locomotion and prehension must be used
      simultaneously to perform a task. Subjects were required to perform five tasks:
      walk normally, walk and pick up a small object, walk and pick up a large object,
      pick up a small object from a stationary standing position, and pick up a large
      object while standing. The grasping and walking movements were videotaped and the
      frequencies of various behaviors were observed (type of grasp, location of
      contact with the object, support leg during contact with the object, timing of
      gaze toward object). Characteristics of the grasp were influenced by object size,
      not by whether the subject was walking. Gaze was shifted to the object before
      initiation of reach and this pattern was not influenced by size of the object or
      movement of the subject. Finally, subjects preferred using an ipsilateral support
      leg while generating the reach, which is a deviation from normal gait patterns.
      Findings indicate that the motor control system may be hierarchically organized
      in such a way that stability of the lower limbs supersedes the control of the
      movement patterns of an upper limb.

PMID- 8570351
TI  - Relationship between adherence to exercise and scores on extraversion and
      neuroticism.
AB  - A sample of 116 subjects were classified as adherers or drop-outs on the basis of
      exercising at an on-campus exercise facility over 1 yr. Scores on the Eysenck
      Personality Inventory showed that adherers did not differ from drop-outs in
      scores on extraversion; however, drop-outs recorded significantly higher
      neuroticism scores than adherers.

PMID- 8570352
TI  - Balance deficits accompanying renal disease are related to diabetic status.
AB  - Balance deficits were examined in a sample of kidney-transplant candidates (60
      men, 30 women) using an ordinal scale. Normal performance was defined as
      unilateral standing for more than 20 sec. Only 52% of the subjects balanced
      normally. A significant relationship between balance performance and diabetic
      status was found. Diabetic patients were more likely to show impaired balance.
      This finding is consistent with prior reports of gait and strength deficits among
      kidney-transplant candidates.

PMID- 8570353
TI  - Spatial concepts and perception of physical and diagrammed scenes.
AB  - The accessibility of objects in mental spatial frameworks depends on their
      relation to the spatial axes of the world and people's typical interactions with
      space. The current study investigated perception of space. Subjects viewed either
      a physical model of a person surrounded by objects (Exp. 1) or diagrams of scenes
      (Exp. 2). Subjects named objects at directions from their own external
      perspective. For physical scenes, subjects were faster to name objects at
      Above/Below locations, followed by Front/Behind locations, followed by Left/Right
      locations. This finding indicates that subjects used spatial frameworks to locate
      objects perceptually. For diagrams, response times to name objects did not
      conform to this pattern, perhaps because the spatial axes of a diagram do not
      correspond to stable spatial axes of the world.

PMID- 8570354
TI  - Lateralization of perceptual closure ability.
AB  - The present study investigated lateralization of perceptual closure ability. A
      zero-power, partially occluded, soft contact-lens system was used to lateralize
      visual input. This technique has been shown to create reliable artificial visual
      field deficits when used in situations offering unlimited duration of stimulus
      exposure. The Street Gestalt Completion Test was administered to 18 right-handed
      men with no history of head trauma, neurological disorders, or familial
      sinistrality. Using repeated-measures analyses, and controlling for age, we found
      no significant hemispheric advantage for either speed or accuracy of performance.

PMID- 8570355
TI  - Anxiety in elderly hearing impaired persons.
AB  - The association between experiences of hearing impairment and signs of anxiety in
      42 elderly hearing impaired patients at a hearing aid centre was investigated.
      Subjects completed the Hearing Coping Assessment, the Beck Anxiety Inventory, and
      an audiometric test of hearing. Analysis showed low scores on anxiety and hearing
      problems compared with other studies. Moreover, scores on anxiety did not
      correlate with pure tone thresholds for hearing but with self-reported hearing
      problems (r = .31). Anxiety is important, but it is possible that signs of
      depression are more strongly related to self-perceived hearing handicap.

PMID- 8570356
TI  - Depressed men's lower ability to interpret nonverbal cues: a preliminary study.
AB  - The ability to interpret nonverbal facial cues was tested with 20 depressed males
      prior to treatment. Each subject and matched control was asked to interpret
      videotaped facial cues of individuals engaged in a gambling task. Interpretive
      ability was significantly lower for the nontreated depressed white men than for
      their matched controls.

PMID- 8570357
TI  - Performance study involving a force-reflecting joystick for spastic individuals
      performing two types of tracking tasks.
AB  - 10 upper-extremity spastic subjects and 10 normal subjects were studied with a
      force-reflecting joystick in the performance of a continuous time-tracking task
      as well as an acquisition task termed, "Fitts' Law." Certain force-reflection
      paradigms, in a spatial sense, allowed the spastic subjects to obtain performance
      proficiency near levels of the normal subjects as measured by a capacity metric.

PMID- 8570358
TI  - Psychological well-being of participants in wheelchair sports: comparison of
      individuals with congenital and acquired disabilities.
AB  - Differences in psychological well-being between participants in wheelchair sport
      with congenital (n = 50) and acquired (n = 43) disabilities were examined.
      Psychological well-being was assessed by scores on mood, trait anxiety, self
      esteem, and mastery. Analysis showed that the group with acquired disabilities
      had a more positive general mood, higher self-esteem and mastery, and lower trait
      anxiety than the group with congenital disabilities. This suggests that sports
      participants in wheelchairs who acquired their disabilities later in life have
      more positive scores on psychological well-being than those with congenital
      disabilities.

PMID- 8570359
TI  - Representation of mental imagery functions.
AB  - A questionnaire was administered to 250 undergraduates to study their conceptions
      about the efficacy of mental images in thinking. Analysis showed that subjects
      rated differently the usefulness of visual imagery according to the kind of
      content rather than the mental process involved.

PMID- 8570360
TI  - Ambulatory status of children with cerebral palsy: a retrospective study.
AB  - The purpose of this study was to examine the association between (a)
      nonambulatory status of 19 children with spastic quadriplegia at age 4 years with
      current ambulatory status and (b) nonambulatory status among these children at
      age 7 years and ultimate development of independent ambulation, using the
      physical therapy records. All continued to be nonambulatory at 7 years and are
      currently. The results suggest (a) a relationship between nonambulatory status at
      age 4 years and ultimate ambulatory status for children with spastic quadriplegia
      and (b) remote prospects for the development of independent ambulation in such
      children who are nonambulatory at age 7 years.

PMID- 8570361
TI  - Conjugate eye movements: comparison of cerebral palsied and normal adults.
AB  - Stimulus-driven binocular pursuit and saccadic movements (+/- 4 degrees, +/- 8
      degrees; 0.3 Hz, 0.5 Hz) were measured in 6 cerebral palsied adults and 5 normal
      adults using a head-free corneal reflection technique. Correlation coefficients
      for binocular position and r2 were calculated; the latter were pooled for each
      group into 6 categories of eye movement: horizontal and vertical triangle and
      sine wave pursuit and saccades. The differences between the group means r2 in
      each category were tested by the Mann-Whitney U. The eye positions were
      statistically less conjugate for the cerebral palsy group in all categories. The
      differences and similarities between the groups are discussed with regard to
      neural and muscular control, visuomotor development, and organization of the
      visuomotor system.

PMID- 8570362
TI  - Factors influencing involvement in farm accidents.
AB  - A self-administered questionnaire completed by 683 male farmers showed
      individuals incurring a farming-related injury more likely to score higher on a
      measure of personal risk-taking and to believe that accidents were inevitable
      (fatalism). Specific safe farming practices--wearing protective clothing and
      operating machinery safely--were associated with lower likelihood of injury.
      Traditional predictors of involvement in accidents (age, exposure to hazards, and
      work experience) were not significant.

PMID- 8570363
TI  - Influence of age, sex, balance, and sport participation on development of sidearm
      striking by children grades K-8.
AB  - The purpose of this study was to examine the contributions of age, sex, balance,
      and sport participation on development of sidearm-striking by children in Grades
      K through 8. Each of 380 boys and 337 girls (ages 4-14 years), enrolled in a
      medium-size school system in southeastern Maine, was individually assessed on
      side-arm-striking and on static and dynamic balance. All subjects completed a
      survey relative to their participation in school or community-sponsored sports.
      To assess the independent effects of age, sex, static balance, dynamic balance,
      and sport participation within each grade, data were subjected to multiple
      regression analysis. Development of mature striking was associated with sex; boys
      performed better at all grades except in Grade 5 where the percentage of girls
      showing a mature sidearm-striking pattern approximated that of boys.

PMID- 8570364
TI  - A difference in heights and weights between right-handed and left-handed bowlers
      at cricket.
AB  - Right-handed pitchers have been shown to be significantly taller and heavier than
      left-handed pitchers. An analysis of 113 professional cricketers in England
      showed a similar difference between right-handed and left-handed bowlers. On
      average the right-handers were 1.05 in. taller and 8.30 lb. heavier than the left
      handers, differences which were close to significance at the 5% level with this
      small n.

PMID- 8570365
TI  - Explaining exercise behavior and satisfaction with social exchange theory.
AB  - This study tested the hypothesis that the variables specified by social exchange
      theory (perceived rewards of exercising, perceived costs of exercising, social
      and tangible investments, and available alternative activities) are associated
      with exercise behavior and satisfaction. 190 health club members completed a
      questionnaire assessing attitudes toward exercise, exercise behavior, and
      demographic information. Exercise frequency and satisfaction were regressed on
      the social exchange theory variables and demographic covariates. Exercise
      satisfaction, the number of investments in exercise, and the number of available
      alternative activities were significantly related to exercise frequency, and the
      number of perceived rewards of exercise and the number of investments were
      significantly related to exercise satisfaction. These results suggest that social
      exchange theory is useful for explaining exercise behavior.

PMID- 8570367
TI  - Sports skill classification, gender, and perceptual style.
AB  - This study was designed to examine the relationship of sport classification and
      gender to perceptual style. 102 male and female undergraduate students from open
      skilled, closed-skilled and nonathletic groups were administered the Rod and
      Frame Test and the Embedded Figures Test. Analysis of variance indicated men to
      be more field independent than women on the Rod and Frame Test, while there were
      no gender differences on the Embedded Figures Test. Athletes performing open and
      closed skills scored significantly more field independent on the Rod and Frame
      Test than the nonathletes. There were no significant differences among the groups
      on the Embedded Figures Test. No correlation between the two measures of
      perceptual style was obtained.

PMID- 8570366
TI  - Effects of positive attitude toward giving a speech on cardiovascular and
      subjective fear responses during speech in anxious subjects.
AB  - 40 speech-anxious subjects were asked to deliver four speeches during the
      experiment. The conditions varied according to whether the subjects maintained a
      positive or neutral attitude toward speech prior to each presentation. Heart rate
      and self-reports of fear were measured during the experiment. Maintaining a
      positive attitude prior to delivering a speech reduced both subjective anxiety
      and cardiovascular responses.

PMID- 8570368
TI  - Patterns of limb laterality and gross-motor agility in children.
AB  - This study examined the association of nine patterns of limb preference
      (combination hand/foot), described as congruent or cross-lateral, with gross
      motor agility of 302 4- to 6-yr-old boys. Based on contemporary reports of
      handedness and motor coordination, it was hypothesized that persons exhibiting a
      right-hand/foot congruent pattern would outperform their peers in other groups.
      However, analyses indicated no significant differences on total motor performance
      between groups with different limb patterns. Further nonsupport of the hypothesis
      was evident since the best performance was exhibited by the mixed-hand/left-foot
      group. In view of past studies and these results, it appears that additional
      inquiry is warranted before any consensus regarding the association between limb
      laterality and motor coordination can be established.

PMID- 8570369
TI  - Subject-controlled performance feedback and learning of a closed motor skill.
AB  - Research on knowledge of results and knowledge of performance has been directed
      toward identification of the optimal schedule for administering feedback. The
      purpose of this investigation was to assess whether a schedule based on
      performance feedback controlled by the learner would be a more effective means of
      delivering feedback than any predetermined or random schedule. Participants were
      randomly assigned to one of five conditions: (a) control group receiving no
      performance feedback, (b) 50% relative performance feedback, (c) summary
      performance feedback, (d) subject-controlled performance feedback, and (e) yoked
      control group. Data were collected during an acquisition phase (four blocks of 10
      trials) and a retention phase (two block of 10 trials) in which subjects
      performed an underhand ball toss. Repeated-measures analyses indicated
      significant main effects for the absolute error (AE). Participants in the subject
      controlled performance feedback condition performed significantly better on both
      retention trials than the other groups. Analysis suggests that a feedback
      schedule which is controlled by the learner may be a more effective means of
      delivering augmented feedback than other schedules which have been examined.

PMID- 8570370
TI  - Association between intermale social aggression and cellular density within the
      central amygdaloid nucleus in rats with lithium/pilocarpine-induced seizures.
AB  - Aggressive behaviors (numbers of bites/hour) within groups (ns = 8) of normal
      rats and rats in which seizures had been induced by a single systemic injection
      of lithium/pilocarpine were observed for 11 successive, 1-hr, periods. Mean
      numbers of neurons and glial cells were counted for 10 different nuclei of the
      amygdala for 16 different brains (8 control; 8 seizure). Although there was no
      significant difference found between rats with chronically induced seizures and
      controls for the numbers of neurons per area within the central medial amygdaloid
      nucleus, the neuronal density was correlated significantly (.92) with mean
      numbers of bites per hour for the chronically epileptic group only. The
      hypothesis that seizure-induced damage within proximal amygdaloid nuclei
      disinhibits the central nucleus and encourages aggression was supported.

PMID- 8570371
TI  - Evidence that transcendental meditation does not produce cognitive kindling: a
      comment.
AB  - This comment on Persinger's paper published in this journal in 1994 includes 4
      studies not cited by Persinger. Each supports the inference of better health of
      those who practice Transcendental Meditation.

PMID- 8570372
TI  - Comparison of two orientation systems for indoor travel of blind persons with
      mental retardation.
AB  - Two blind women affected by severe mental retardation were exposed to two
      previously developed orientation systems. One of the systems was based on
      acoustic cues, the other on vibratory feedback. The aim was to assess the
      relative effectiveness of the two systems. Data indicated that the acoustic
      system ensured a higher frequency of correct moves for one of the subjects and a
      more rapid performance of the moves for both subjects. The findings are reviewed
      in relation to the characteristics and applicability of the systems.

PMID- 8570373
TI  - Lucid dreaming and control in waking life.

PMID- 8570374
TI  - The false recognition of mood-matched and mood-opposite words in a memory task:
      introduction of a delayed testing condition.
AB  - This report details the results of an extended replication with 74 new subjects
      of Whissell, Marshall, and Whissell's 1990 study. In confirmation of the original
      study and two follow-up studies, subjects tended to recognize words falsely as
      having belonged to a list if these words matched the emotional mood of the list
      but not if they had an opposite mood (mood was defined in terms of the
      pleasantness and activity dimensions of emotion). For delayed testing (one week),
      this effect was even more pronounced as false recognitions for mood-matching
      words become as frequent as correct recognitions for words actually on the list.

PMID- 8570375
TI  - Accident history and perceived risk of injury as factors influencing fatalism
      about occupational accidents.
AB  - In a survey of 263 employed men and women fatalism about workplace accidents was
      rated highest by respondents who perceived that their current jobs were dangerous
      and posed a high risk of personal injury. An individual's prior accident history
      was not associated with ratings on Accident Fatalism.

PMID- 8570376
TI  - Test-retest reliability of a psychometric instrument designed to measure physical
      therapy students' burnout.
AB  - The purpose of this study was to assess the reproducibility of scores on an
      instrument designed to measure physical therapy students' burnout. Physical
      therapy students (28 juniors and 28 seniors) completed an adapted educator's
      version of the Maslach Burnout Inventory on two occasions within a week interval.
      At each testing session, a separate score was obtained for each student for the
      three (emotional exhaustion, depersonalization, and personal accomplishment)
      subscales of the instrument. These scores, analyzed with a two-factor repeated
      measures analysis of variance, indicated a significant difference in the personal
      accomplishment score between the junior and senior students during the two time
      frames. Scheffe post hoc tests showed that the junior students reported higher
      personal accomplishment affect at both testing sessions than the senior students.
      Both junior and senior students reported higher personal accomplishment at retest
      than at baseline testing. A test-retest reliability coefficient of .850 was
      obtained for the Depersonalization subscale; .907 and .715 were obtained for the
      Emotional Exhaustion and Personal Accomplishment subscales, respectively.

PMID- 8570377
TI  - Head position and spinal position as determinants of perceived emotional state.
AB  - A sample of 60 first-year psychology students judged the emotional state of 21
      drawn figures and completed the Adjective Checklist and a mood questionnaire. The
      judgments were affected by the interaction between head position and spinal
      position of the figure. Each figure was associated with a unique pattern of
      emotions, and the judgments given were not influenced by the subjects' own
      emotional state.

PMID- 8570378
TI  - Placebo washout is not a meaningful part of antidepressant drug trials.
AB  - Most trials testing the effectiveness of psychotropic drugs begin with a placebo
      washout phase. Hypothetically this technique rids studies of placebo responders
      before randomization of subjects to drug and placebo groups. In theory, this
      lowers the level of response to placebo in the study and magnifies the
      superiority of the response to medication. An analysis of 10 years of research
      literature demonstrates that the washout technique does not do what it was
      designed to do in antidepressant studies. Within placebo or drug groups neither
      measures of depression nor dropouts were affected by including a preliminary
      washout in the design. The findings are consistent with the two other studies
      that have addressed this issue.

PMID- 8570379
TI  - Perceived exertion and metabolic responses of women during aerobic dance
      exercise.
AB  - The relationship between ratings of perceived exertion (RPE) and metabolic
      responses was examined during aerobic dance exercise with combined arm and leg
      movements. 16 women with previous aerobic dance instructional experience
      performed three consecutive trials of 8 min. each of aerobic dance exercise at a
      cadence of 124 and 138 beats.min.-1. Estimates of RPE reported at the end of each
      trial were significantly different across the trials while heart rate and %
      maximum heart rate were significantly different between Trials 1 and 3.
      Correlations and partial correlations between RPE and all metabolic variables
      were not significant across trials and with trials combined except for
      ventilation. Results indicated that RPE should not be used singularly as an
      indicator of exercise intensity during aerobic dance exercise.

PMID- 8570380
TI  - The influence of orthosis stiffness on paraplegic ambulation and its implications
      for functional electrical stimulation (FES) walking systems.
AB  - This study examines the evidence which supports the importance of maintaining
      relative abduction for effective reciprocal walking in high level paraplegic
      patients. In comparisons of orthoses, where this can only be achieved
      mechanically, those with higher lateral rigidity consistently showed greater
      levels of walking efficiency. The influence on hybrid systems of functional
      electrical stimulation (FES) of the gluteal muscles, where the primary function
      is to maintain abduction, also showed reductions in overall energy cost,
      reductions in upper limb effort, or both. Examination of the effect of increasing
      lateral rigidity of a purely mechanical orthosis by 10% showed that significant
      energy cost reductions were achieved (30% reduction in Physiological Cost Index)
      for patients with thoracic lesions experienced in reciprocal walking. A review of
      FES research suggested that for the modern healthcare sector the cost
      effectiveness of purely mechanical systems make them an attractive means of
      routinely providing the functional and therapeutic benefits of walking for high
      level paraplegic patients. In the prevailing climate of strict budgetry control a
      case is made for concentrating more research resources on improving still further
      walking efficiency, and resolving the outstanding problems of functionality and
      cosmesis in such systems for reciprocal walking.

PMID- 8570381
TI  - Modified fracture brace for tibial fracture with varus angulation: a case report.
AB  - Sarmiento introduced the functional fracture brace for the management of tibial
      shaft fracture in 1963. However, tibial angulation with varus deformity cannot be
      prevented or corrected by such a device. In this paper, a case of tibial shaft
      fracture with varus angulation treated with a modified below-knee fracture brace
      was reported.

PMID- 8570382
TI  - Design and manufacture of a high performance water-ski seating system for use by
      an individual with bilateral trans-femoral amputations.
AB  - A high performance seating unit has been produced for a water-skier with
      bilateral transfemoral amputations. The system, in which the user sits whilst
      skiing, has helped the client to further her sporting career and enabled her to
      compete successfully at the highest levels of disabled water-skiing competition.

PMID- 8570383
TI  - Driving appliances for upper limb amputees.
AB  - The advice given to upper limb amputees in the United Kingdom with regard to the
      use of driving appliances has often been somewhat variable. At best a full
      rehabilitation package has been provided, including the fitting of the appliances
      to the person's vehicle and contact with the driver's instructor, to the other
      extreme of issuing driving appliances to patients with no instruction at all.
      Though upper limb amputations are not a relevant or prospective disability, all
      drivers with a "limb disability" are legally required, in the UK, to declare
      changes in their physical state to the Driver and Vehicle Licensing Agency. This
      study examines the current usage of driving appliances. It was found that the
      level of upper limb loss has little effect on where the driving appliance is
      placed or on any other aspect of driving method used.

PMID- 8570384
TI  - Carbon fibre and fibre lamination in prosthetics and orthotics: some basic theory
      and practical advice for the practitioner.

PMID- 8570385
TI  - Functional outcomes in a lower limb amputee population.
AB  - This paper reports an evaluation of 132 patients seen at the Nova Scotia
      Rehabilitation Centre amputee programme during a 24-month period, carried out to
      evaluate the programme's effectiveness. In addition to a review of charts, a
      questionnaire was used (85% return rate) to help determine functional outcomes.
      The patient profile revealed a 3.4:1 male-to-female ratio and an average age of
      64.8 +/- 13.0 years. The average overall training time was 44.0 +/- 26.5 days. Of
      the respondents, 65.5% wore their prosthesis at least 9 hours/day, 11.5% wore it
      at least 4 hours/day, and only 16.1% were no longer using their prosthesis. The
      programme's effectiveness appears to compare well with that of others reported in
      the literature.

PMID- 8570386
TI  - Validation of spiral CT and optical surface scanning for lower limb stump
      volumetry.
AB  - Spiral X-ray Computed Tomography (SXCT), Optical Surface Scanning (OSS), and
      hydrostatic weighing methods were used to measure stump volume of trans-tibial
      amputees. The precision and accuracy of these methods were assessed in a
      validation study. A repeated measures analysis of variance statistical design was
      employed that required each participant to be measured (scanned) twice at each of
      two separate measurement sessions. For OSS and SXCT, each scan was segmented
      twice to determine intra-observer error. Plaster cast replicas of subject stumps
      were formed by certified prosthetists to serve as a reference standard. Accuracy
      (bias) of SXCT and OSS was determined by comparison to volumetry by hydrostatic
      weighing. Ten trans-tibial amputees were recruited for this study and nine
      completed both sessions. Plaster replica measurement precision error relative to
      the mean was found to be less than 1% for all modalities. The precision was
      slightly inferior on subjects, 1.1% and 2.2% error for hydrostatic weighting and
      OSS respectively, due to patient instability during measurement, but was better
      with SXCT where the subjects' stumps were stabilized during scan acquisition. The
      OSS and SXCT methods offer advantages over hydrostatic weighing and other
      volumetry methods since the volume data are represented digitally and can be
      analyzed in multiple ways. SXCT enables study of the stump and its internal
      tissues with the prosthesis in place. It was found that SXCT is comparable to
      hydrostatic weighing in both precision and accuracy. While OSS had a high
      precision and reproducibility, it was found to have an associated bias.

PMID- 8570387
TI  - [MR angiography in intrathoracic masses: evaluation of the superior vena cava,
      its major branches and their relation to the mass].
AB  - MR angiography (MRA) of the thorax was evaluated in six healthy volunteers and 48
      patients with an intrathoracic mass potentially infiltrating to the superior vena
      cava and/or its major branches. It was also compared with CT, spin echo MRI and X
      ray venography. Three methods were used for MRA: sequential 2D-TOF MRA with
      presaturation band over the heart, 3D-MRA with bolus administration of Gd-DTPA in
      a single breath-hold and sequential 2D-TOF MRA with administration of Gd-DTPA.
      The major vessels themselves and their relation to the mass were clearly
      visualized on MRA in all volunteers and patients. Since original MRA demonstrated
      these vessels more clearly than projection MRA in our series, we considered that
      interpretation of MRA should be based mainly on original MRA. MRA generally could
      visualize the vessels as well as the other imaging modalities, and was sometimes
      superior to them. In conclusion, MRA is a non-invasive and effective method for
      the evaluation of major vessels and their relation to the mass in patients with
      an intrathoracic mass.

PMID- 8570388
TI  - [Percutaneous placement of intraluminal stent-graft for aortic dissection:
      experimental study].
AB  - Highly porous fabric vascular grafts fabricated of ultrafine polyester fibers
      (UFPF-graft; porosity, 7,000 ml, 9,000 ml, 11,000 ml at 120 mmHg) were attached
      between two Gianturco stents connected with two stainless steel struts. UFPF
      grafts with two Gianturco stents were placed into the aortas of six adult mongrel
      dogs without firm contact with the luminal surface. From two days to four months
      after placement, all the UFPF-grafts were completely sealed with fresh thrombus
      or neointima. Within two months, complete endothelialization was observed on both
      surfaces of the neointima. In three dogs, aortic dissections were created
      experimentally. Then an UFPF-graft (porosity, 9,000 ml) with two Gianturco stents
      was placed at the site of entry of the dissection, followed by additional
      Gianturco stents to expand the UFPF-graft. X-ray angiography showed that the
      entries were closed immediately after placement, and false lumens disappeared
      within one hour after placement. These results indicated that the method has the
      possibility of treating aortic dissection with complete sealing of the fabric by
      the neointima.

PMID- 8570389
TI  - [Three-dimensional helical CT angiography of the abdomen].
AB  - To evaluate the quality of three-dimensional (3D) images of the abdominal
      vasculature acquired using enhanced helical CT, 3D reconstructions were performed
      for 43 examinations (38 patients). Twenty-one of 43 examinations were also
      reconstructed by Maximum Intensity Projection (MIP). The CT scanner employed was
      the Toshiba Xforce. Helical CT data were acquired using up to 20 continuous 1.5
      sec rotations with an X-ray beam width of 5 mm and a couchtop movement speed of 5
      to 10 mm/1.5 sec. Axial images were reconstructed at a section interval of 2 mm.
      Optimal protocol on enhanced helical CT was as follows: Iopamidol 300 mg I/ml was
      administered intravenously using a biphasic technique (3-4 ml/sec for the initial
      100 ml, followed by 0.7-1.5 ml for the remaining 50 ml), and delay times of the
      early and late phases were 25-35 and 90 sec, respectively. Aortic branches were
      clearly demonstrated on early phase, while portal branches were well defined on
      late phase. In the visualization of abdominal vessels, 3D images were nearly
      equal to MIP images. However, for anteroposterior images, MIP images were
      superior to 3D images in quality, because 3D images had some longitudinal
      direction artifacts. Three-dimensional images were considered to be useful for
      correctly evaluating overlapping abdominal vasculatures. From the above results,
      3D and MIP images of the abdominal vasculature obtained using enhanced helical CT
      were considered to compensate for each other.

PMID- 8570390
TI  - [Selective intra-arterial injection of calcium for localization of insulinomas:
      proposed new criteria].
AB  - To elucidate whether noninvasive arterial stimulation venous sampling (ASVS) is
      helpful for localizing insulinomas, calcium gluconate (0.02-0.025 mEq Ca2+/kg)
      was injected directly into the gastroduodenal, splenic and superior mesenteric
      arteries of six patients with episodic hypoglycemia. In all six patients, there
      was a greater than 26-fold increase in serum insulin levels in blood samples
      obtained from the hepatic vein after the infusion of calcium into the artery
      supplying the tumor. However, in four of the six patients, such an injection into
      an artery not supplying the tumor resulted in a greater than twofold increase in
      insulin concentration. Accurate localization of the insulinomas was verified at
      surgery in all patients. We believe that these false positive results were caused
      mainly by the influx of calcium via branches of intrapancreatic anastomoses. In
      order to minimize false positive results, we have recommended the following new
      criteria for ASVS: maximum insulin concentrations exceeding 150 microU/ml in
      blood samples obtained from the hepatic vein, and greater than twofold increases
      in insulin concentration. We concluded that noninvasive ASVS is helpful in
      determining the location of insulinomas.

PMID- 8570391
TI  - Clinical evaluation of congenital muscular torticollis by using MR imaging.

PMID- 8570392
TI  - [Scirrhous gastric carcinoma: utility of computed tomographic diagnosis].
AB  - Fifty gastric carcinoma lesions were classified into three groups depending on
      their morphologic characteristics on incremental dynamic computed tomography
      (CT). Two-layered tumors (23 cases) showed both an outer layer of low attenuation
      and a thick inner layer of high attenuation. Furthermore, they were classified
      into two subgroups depending on the thickness of the outer layer. Two-layered
      tumors showing a thick outer layer (13 cases) were all scirrhous carcinomas. The
      mean thickness was 11.05 +/- 3.38 mm for the outer layer, and 4.40 +/- 1.92 mm
      for the inner layer. The thick outer layer corresponded histopathologically to
      the layer submucosal to the serosa, and the thick inner layer, to the mucosal
      layer. Two-layered tumors showing the thin outer layer (10 cases) were all non
      scirrhous carcinomas. The mean thickness was 1.62 +/- 0.47 mm for the outer
      layer, and 12.34 +/- 8.68 mm for the inner layer. Tumors of high attenuation (12
      cases) and tumors of low attenuation (15 cases) were also nonscirrhous
      carcinomas. In conclusion, all scirrhous carcinomas showed both a thick outer
      layer and a thick inner layer, whereas non-scirrhous carcinomas did not have
      appearance. This new classification can serve as a guideline for predicting
      scirrhous carcinoma on the basis of CT findings.

PMID- 8570393
TI  - [Whole mediastinal irradiation with or without entire hemithoracic irradiation
      for invasive thymoma].
AB  - We retrospectively reviewed the case histories of 45 patients with invasive
      thymoma who underwent postoperative or definitive radiotherapy. Patients in stage
      II or stage III were classified according to the treatment volume as follows: a)
      those who received irradiation confined to the primary tumor site with a generous
      margin (involved field group, n = 17) and b)those who received prophylactic whole
      mediastinal irradiation with or without entire hemithoracic irradiation
      (prophylactic group, n = 21). Seven recurrences were observed among the involved
      field group, while all patients in the prophylactic group were relapse-free and
      alive after a median follow-up interval of 50 months. Major side effects were
      observed in two patients who received entire hemithoracic irradiation. One
      developed severe pneumonitis resulting in lung fibrosis that required
      hospitalization, while the other developed nephrotic syndrome of unknown cause.
      We conclude that whole mediastinal irradiation with or without entire
      hemithoracic irradiation can be used as a treatment of choice for postoperative
      invasive thymoma.

PMID- 8570394
TI  - [A study of acquisition time using compartment analysis with 99mTc-GSA liver
      scintigraphy].
AB  - 99mTc-galactosyl human serum albumin (99mTc-GSA) is a newly developed receptor
      binding agent specific for the asialoglycoprotein receptor, which resides
      exclusively on the plasma membrane of mammalian hepatocytes. Liver scintigraphy
      using 99mTc-GSA was performed on 13 patients with liver disease. Dynamic data
      were obtained by gamma camera during 40 min after the intravenous injection of 3
      mg (185 MBq) of 99mTc-GSA. Heart and liver time activity curves with acquisition
      times of 40,30 and 20 min were created, and two different compartment analyses
      were examined. One was a nonlinear five-compartment model adopting the Michaelis
      Menten type for the transfer of 99mTc-GSA from hepatic blood to receptor, and the
      other was a linear five-compartment model assuming a linear rate constant (P(2)*)
      for the transfer of 99mTc-GSA. The maximum removal rate obtained by the nonlinear
      model, P(2), was found to be independent of the change in acquisition time, while
      the maximum removal rate obtained by the linear model, P(2)*.Km, which was given
      by the product of P(2)* and the Michaelis constant Km, increased with shortening
      acquisition times from 40 to 20 min. For both models, the liver blood flow rate
      decreased with shortening acquisition time. The maximum removal rate and liver
      blood flow rate obtained by the linear model were significantly correlated with
      those obtained by the nonlinear model. It was concluded that linear model with an
      acquisition time of 20 min was applicable to liver scintigraphy with 99mTc-GSA.

PMID- 8570395
TI  - [Dose-volume histogram comparison among techniques of linac stereotactic
      radiosurgery].
AB  - The aim of this study was to analyze the three-dimensional dose distributions
      produced by various techniques used in current radiosurgery treatments by means
      of dose-volume histograms (DVH). Off-center ratio and tissue-peak ratio from 6-MV
      X-rays through additional cylindrical collimators were measured in advance for
      dose calculation. The use of the diamond detector and beam profile film dosimetry
      in small fields were certified. The impact of arc number, arc geometry, and field
      size on the dose distribution in a spherical phantom was evaluated through the
      use of DVH. These were calculated for a) four arc irradiations with collimator
      sizes of 5, 10, 20 and 30 mm in diameter, and b) for single-plane rotation, four
      or eleven multiple non-coplanar convergent arcs, dynamic rotation and
      precessional converging radio-therapy (PCR) with a field size of 20 mm. PCR is
      performed in the sitting position with the patient seated on a special treatment
      chair, which is rotating continuously while the gantry moves from the top to the
      center of the chair rotation. Most of the differences between techniques were
      found in a range of less than 40% of the maximum dose. Multiple non-coplanar
      convergent arcs with four or eleven arcs and PCR performed similar result in DVH,
      while single-plane rotation revealed almost unacceptably shallow dose falloffs.
      The DVH of dynamic rotation was between that of single-plane rotation and the
      other three methods.

PMID- 8570396
TI  - [Study of anti-tumor effects of hyperthermia combined with hydralazine on
      experimental tumor].
AB  - We analyzed tumor growth delay in experimental tumors after hyperthermia alone,
      hydralazine (HDZ) injection alone and the combination of these modalities. We
      also analyzed the energy parameter (ATP/Pi ratio) obtained by 31P-MRS (magnetic
      resonance spectroscopy). The purpose of this study was to evaluate the usefulness
      of 31P-MRS as an index of anti-tumor effect. FM3A tumor cells were transplanted
      subcutaneously in the hind legs of C3H/He mice. We dipped the tumors into a
      heated circulating water bath. 31P-MRS was performed with a CSI spectrometer. The
      anti-tumor effect obtained with HDZ alone was insignificant, but combined
      treatment with hyperthermia and HDZ had a significant synergistic effect. The
      ATP/Pi ratios for all groups treated separately with HDZ or hyperthermia were not
      different from the control, but the ATP/Pi ratio decreased after combined use of
      these agents. There was a significant correlation between the decrease in ATP/Pi
      ratio and tumor growth delay. We observed a direct relation between the delay in
      tumor growth and the decline in ATP/Pi ratio after combined treatment with HDZ
      and hyperthermia. The ATP/Pi ratio 24 hr after treatment may be useful in
      predicting the efficacy of the combined use of HDZ and hyperthermia.

PMID- 8570397
TI  - [Simultaneous intraluminal irradiation and hyperthermia treatment for esophageal
      carcinoma].
AB  - The combination of radiotherapy and thermotherapy has the greatest antitumor
      effect when delivered simultaneously. We developed and have clinically used an
      applicator that enables simultaneous intraluminal irradiation and hyperthermia
      delivery for the treatment of locally invasive esophageal carcinoma. In a phase 1
      study, 40 Gy of external irradiation was delivered followed by simultaneous
      intraluminal hyperthermia and radiotherapy once weekly for three weeks.
      Intraluminal hyperthermia was delivered to the mucosal surface at 42 to 44
      degrees C for 30 minutes. Intraluminal irradiation (3 Gy) was delivered to a
      submucosal depth of 5 mm after the first 15 minutes of hyperthermia. This
      treatment may increase current treatment results for locally invasive esophageal
      carcinoma, which have otherwise been maximized.

PMID- 8570398
TI  - [99mTc pertechnetate scintigraphy for malignant soft-tissue tumors].
AB  - The purpose of this study was to investigate the accumulation of technetium-99m
      pertechnetate (99mTc) in malignant soft-tissue tumors. Twenty-one patients with
      malignant soft-tissue tumors were subjected to 99mTc scintigraphic studies. In 19
      of 21 patients (90%), 99mTc accumulated extensively in the tumors. 99mTc
      accumulation was especially thorough in all cases of MFH and liposarcoma.
      Therefore, 99mTc is useful for the local evaluation of malignant soft-tissue
      tumors.

PMID- 8570399
TI  - [Making a backlight display panel using a personal computer and a laser imager: a
      less expensive and less time-consuming method].
AB  - To make a backlight display panel for a scientific exhibit, we used a
      commercially available laser imager. The MR image was directly transferred from
      the MR apparatus to a personal computer, and other image information was
      transferred through an image scanner or digital camera. Text for the presentation
      was made on the commercially available presentation software Persuasion. It took
      approximately 10 minutes to print out all the panels needed for one exhibit, and
      cost only 3,600 Yen (600 Yen a film).

PMID- 8570400
TI  - [Lowered cholesterol beneficial for vascular endothelium].
AB  - Although it is logical that coronary artery plaque is reduced, or at least the
      stenotic process is inhibited, when blood lipid concentrations are normalised,
      this does not suffice to explain the beneficial outcome of treatment in cases of
      hypercholesterolaemia. Several recent studies have yielded manifest evidence of
      the effects of cholesterol on endothelial function. Via chemical mechanisms the
      endothelium exerts significant regulatory effects-e g, on vascular contractility,
      and intervention in this process offers several possibilities of treating and
      preventing coronary artery disease.

PMID- 8570401
TI  - [The Scandinavian laboratory--a goldmine for public health research].

PMID- 8570402
TI  - [Scandinavian cooperation cannot be replaced by European commitment. Interview by
      Eva Oldinger].

PMID- 8570404
TI  - [A new Nordisk Medicin].

PMID- 8570405
TI  - [European young physicians initiate a social dialog about working hours].

PMID- 8570403
TI  - [Is there a future for the Scandinavian Health Care College?].

PMID- 8570406
TI  - [Health and weather in New York and in Lofoten].

PMID- 8570407
TI  - [Neurotrophic factors in the CNS. Increasing numbers of proteins with clinical
      potential].
AB  - The great Anders Jahre Prize, for 1995, for medical research, is to be shared by
      Professor Lars Olson, Stockholm, and Professor Anders Bjorklund, Lund. Lars Olson
      is one of the pioneers responsible for mapping the neural pathways of the brain.
      He has also systematically studied the mechanisms underlaying nerve cell growth
      and clucidated the growth factors involved. Our knowledge of the proteins
      necessary to neuron survival, nerve fibre growth, and the maintenance of synapses
      is increasing very rapidly. In a long-term perspective, this will open up new
      approaches to the treatment of a number of neuropathological diseases, eg,
      Parkinson's disease, and to the repair of nerve tissue, eg, after stroke.

PMID- 8570409
TI  - Author--what does it mean to be one?

PMID- 8570408
TI  - [Snow-boarding injuries can be prevented].
AB  - The last four winter seasons have witnessed a dramatic increase in the popularity
      of snowboarding. A series of snowboarding injuries treated at University
      Hospital, Umea, predominantly consisted of those sustained by teenage boys, often
      when jumping or losing balance for other reasons. The upper extremities were the
      most common sites of injury, 2/3 of these injuries being fractures. The commonest
      type of lower extremity injury was sprain, and 2/3 of lower extremity injuries
      affected the foremost leg. To prevent injuries, it is recommended that snowboard
      bindings should be modified by the introduction of some sort of release
      mechanism, and enthusiasts should be urged to attend a training course, to use
      soft-shell footwear and to wear gloves with reinforcement protecting the hand and
      wrist.

PMID- 8570410
TI  - Transformation of the nursing workforce.

PMID- 8570411
TI  - Recreating past separations and the employment pattern of nurses, 1900-1940.

PMID- 8570412
TI  - Multiple ideologies and their proposed roles in the outcomes of nurse practice
      settings: the for-profit psychiatric hospital scandal as a paradigm case.

PMID- 8570413
TI  - Cultural diversity: a nursing concept not yet reliably defined.

PMID- 8570414
TI  - The Human Genome Project: an overview of ethical issues and public policy
      concerns.
AB  - The possibilities of advancement from the Human Genome Project seem endless. But
      even though we are amazingly similar genetically to other animals, including the
      mouse, we are uniquely human. And our humanness is our greatest gift. The
      knowledge of genetic linkages and of how life works does not diminish our
      religious beliefs or our value system. Understanding the mechanics of human
      physiology does not decrease the power and beauty of human life. Quite the
      contrary, this knowledge helps to chart the course in a quest to understand what
      it means to be human. Let us honor the beauty and uniqueness of human life by
      making ethically sound decisions surrounding the advances made in this fantastic
      journey called the Human Genome Project.

PMID- 8570415
TI  - Innovative culture shock prescribed for health care.
AB  - Finally, organizations must accept that inefficiencies are often present in
      creative cultures. Resources that were devoted to operating and revenue
      generating functions must be shifted to finance the capacity to be creative. The
      short-term focus of today's organizations blinds them from envisioning the long
      term benefits of fostering creative changes and improvements. When creativity is
      properly managed, meaningful risks may be taken with reasonable costs
      occasionally yielding monumental results.

PMID- 8570416
TI  - The dimensional structure of nursing interventions.
AB  - The derivation and description of the embedded structure undergirding nursing
      interventions are provided in this study. To determine the dimensions of nursing
      interventions, multidimensional scaling was used to analyze similarity ratings
      among classes of interventions. Kruskal's stress formula indicated that the
      embedded structure is composed of three dimensions. To describe the dimensions,
      each intervention class was rated on a 16-attribute pair semantic differential
      scale. Subsequent factor analysis and correlations of the factors with the
      dimensions resulted in the delineation of three dimensions: intensity of care,
      complexity of care, and focus of care.

PMID- 8570417
TI  - Correlates of health-promotion activities in employed Mexican American women.
AB  - The purposes of this study were to describe the health-promoting lifestyle
      behaviors of 397 employed Mexican American women and to compare them with women
      in other published reports that used the Health-Promoting Lifestyle Profile
      (HPLP). Mexican American women had the highest HPLP total scores of all minority
      groups, but lower scores than all predominantly White groups. HPLP self
      actualization and interpersonal support were the highest subscale scores. The
      exercise subscale was the lowest score for all groups, including minorities.
      Canonical analysis revealed two significant canonical variate pairs explaining
      88% of variance. Age, education, self-efficacy, health locus of control (internal
      and powerful others), and current health status made statistically significant
      contributions to all HPLP subscale scores. Study results support previous
      research findings and make an important contribution to understanding the factors
      that influence Mexican American women's health-promoting lifestyle behaviors.

PMID- 8570418
TI  - Factor analysis of the Ways of Coping Questionnaire for African American women.
AB  - The purpose of this study was to determine the factorial structure of the Ways of
      Coping Questionnaire for African American women. A sample of 656 African American
      women living in the southeastern United States, ranging in age from 22 to 64
      years (M = 39.6 years), completed the questionnaire. All were employed, with a
      mean annual income of $24,300. Factor analysis produced three factors, Active
      Coping, Avoidance, and Minimize the Situation, that accounted for 67% of the
      total variance. These factors were compared with the eight factors of the Ways of
      Coping questionnaire reported by Folkman and Lazarus (1980), which was derived
      from a sample of middle-aged White subjects. The factors that emerged suggest the
      need for possible revision of the instrument or the development of a new one.

PMID- 8570419
TI  - The effects of cognitive-perceptual factors on health promotion behavior
      maintenance.
AB  - A causal model that examines the role of cognitive-perceptual factors (control
      over health, self-efficacy, and health status) in health-promoting behavior
      maintenance was tested using a sample of 1,339 women who participated in a two
      wave national health survey. The sample was split to reserve half the data for an
      uncompromised validity test of the model. Initial tests of the causal model
      indicated that the model did not fit the data. A minimally modified model fit the
      observed covariance data and explained about one third of the variance in the
      health-promoting behaviors (self-actualization, health responsibility, exercise,
      and nutrition). Validation of the model with the uncompromised half of the data
      further supported the model. Although the cognitive-perceptual factors were an
      integral part of the model, their effects on particular health-promoting
      behaviors were small in magnitude and contributed little to the explanation of
      the specific health-promoting behaviors or their stability.

PMID- 8570420
TI  - Abuse during pregnancy: associations with maternal health and infant birth
      weight.
AB  - A stratified, prospective cohort analysis was completed on 1,203 African
      American, Hispanic, and white women. All women were assessed for abuse at the
      first prenatal visit and twice more during pregnancy. They were also assessed for
      risk factors of low birth weight using Institute of Medicine correlates.
      Prevalence of physical or sexual abuse during pregnancy was 16% (1 of 6). Abused
      women were twice as likely to begin prenatal care during the third trimester,
      with abuse preceding late entry. Abuse was recurrent, with 60% of the women
      reporting repeated episodes. More severe abuse was significantly correlated with
      lower infant birth weights for all three ethnic groups. Abuse during pregnancy
      was a significant risk for low birth weight as well as maternal low weight gain,
      infections, anemia, smoking, and use of alcohol and drugs. When compared to women
      who were not abused, women abused during pregnancy delivered infants averaging
      133 g less. Abused white women delivered infants with the greatest reduction in
      birth weight.

PMID- 8570421
TI  - A longitudinal comparison of irritable and nonirritable infants.
AB  - Infantile colic is characterized by persistent crying, diminished soothability,
      and excessive activity or restlessness. The purpose of this study was to explore
      the processes underlying the persistent, recurrent irritability by investigating
      behavioral and interactional differences in irritable and nonirritable infants.
      In this two-group longitudinal study, 40 infants and their mothers were followed
      over the first 4 months of life. Statistically significant differences between
      the two groups were found, with the irritable infants demonstrating an increase
      in the amount and intensity of crying, more disruption in sleep-wake states, and
      less synchrony in mother-infant interaction.

PMID- 8570422
TI  - Temporal patterns of heart rate and blood pressure in elders.
AB  - Circadian patterns of heart rate, systolic and diastolic blood pressure, and rate
      pressure product were compared in elders with heart disease (N = 22, mean age 86
      years) and a comparison group (N = 18, mean age 80 years) who did not have a
      cardiac diagnosis. For 4 consecutive days, automated measures of heart rate,
      diastolic and systolic blood pressure, and rate-pressure product were taken every
      2 hours while subjects were awake. Activity-rest patterns were recorded by an
      observer, and demographic and medication profiles were obtained. Data were
      subjected to cosinor analysis, and the groups were compared on rhythmic
      parameters. Although the cardiac subjects were older, in poorer health, less
      active, and more prone to daytime napping, they exhibited more rhythms in rate
      pressure product than did the comparison subjects. The cardiac group also had
      more synchronized oscillation of overt heart rate and systolic blood pressure
      rhythms. These results can be attributed to standardized times of cardiac
      medication administration. Attention to patterns of heart rate and systolic blood
      pressure in elders may suggest more appropriate times of day for conducting
      individual cardiac assessments.

PMID- 8570423
TI  - Evaluation of a new topical anesthetic agent: a pilot study.

PMID- 8570424
TI  - Affect in diabetic women during pregnancy and postpartum.

PMID- 8570425
TI  - Comparison of original and revised scoring systems for the Multiple Affect
      Adjective Check List.

PMID- 8570426
TI  - Stereochemical aspects of pharmacotherapy.
AB  - Over the past 15 years stereoselectivity has become a well-recognized
      consideration in clinical pharmacology. Drugs that have an asymmetric center or
      plane of symmetry within their molecular structure are said to be chiral. They
      are available as pairs of nonsuperimposable mirror images, called enantiomers,
      that share essentially the same physicochemical properties. These three
      dimensional structural differences, however, can translate into enantiospecific
      pharmacologic or pharmacokinetic properties, which may be important in
      understanding the clinical pharmacology of chiral drugs. Most chiral drugs are
      available as the racemate, in which equal proportions of the two enantiomers are
      administered concurrently. The pharmacologic and disposition properties of many
      chiral drugs are documented to be stereospecific, and this has influenced the
      regulatory requirements for the approval of new drug candidates. Due to this
      influence on new drug development, the possible issues surrounding racemic drugs
      will undoubtedly affect the types of pharmaceuticals that are used clinically in
      the next century. Accordingly, considerable advances have been made in producing
      optically pure drug. It should be emphasized, however, that stereochemically pure
      drugs are not necessarily superior to the respective racemates.

PMID- 8570427
TI  - The effect of supplemental dietary fat on plasma cholesterol levels in lovastatin
      treated hypercholesterolemic patients.
AB  - STUDY OBJECTIVE: A validation study was conducted first to test assumptions about
      the effect of saturated and unsaturated dietary fat supplements. The second study
      was conducted to determine the effect on blood cholesterol levels of saturated
      and unsaturated fat supplements in patients who followed a low-fat diet and were
      administered lovastatin. DESIGN: Randomized, crossover design, with three periods
      in the first study and four in the second study, each lasting 6 weeks. SETTING:
      Cholesterol Research Center. PATIENTS: The first study evaluated adults with
      total cholesterol levels between 200 and 280 mg/dl (5.172 and 7.241 mmol/L). The
      second study included adults with low-density lipoprotein (LDL) cholesterol
      levels above 160 mg/dl (4.138 mmol/L). INTERVENTIONS: Fat supplements with either
      coconut or canola oil were delivered to patients in oatmeal-raisin cookies.
      MEASUREMENTS AND MAIN RESULTS: In the validation study, patients' mean
      prerandomization total cholesterol level of 222 mg/dl was reduced to 213 mg/dl
      with canola oil and increased to 233 mg/dl with coconut oil cookies (p = 0.0038).
      In the second study the mean prerandomization total cholesterol level of 214
      mg/dl was decreased to 199 mg/dl with canola oil and to 208 mg/dl with coconut
      oil cookies (p = 0.2342). The LDL cholesterol levels changed in a similar fashion
      in both studies. CONCLUSIONS: Changes in total and LDL cholesterol levels in the
      validation study were expected based on established effects of saturated and
      unsaturated fatty acids, but changes in these levels in lovastatin-cookie study
      were not expected. They could have occurred because lovastatin reversed the
      effect of saturated fats and enhanced the effect of unsaturated fats.
      Alternatively, they may have been due to enhanced bioavailability of lovastatin
      when administered with a high-fat diet. These findings must be confirmed.

PMID- 8570428
TI  - Age and carotid artery occlusive disease are important determinants of cerebral
      blood flow changes after antihypertensive therapy.
AB  - STUDY OBJECTIVE: To determine the short-term effects of antihypertensive therapy
      on cerebral blood flow (CBF). DESIGN: Prospective, observational study. SETTING:
      A university-affiliated teaching hospital. PATIENTS: Twenty-four patients (age
      range 53-85 yrs) with chronic hypertension, nine of whom had carotid artery
      occlusive disease (CAOD). INTERVENTIONS: The CBF (xenon-133 inhalation technique)
      and blood pressure were measured before and at 60 minutes after administration of
      antihypertensive therapy. MEASUREMENTS AND MAIN RESULTS: Age was inversely
      related to the change in CBF in patients with CAOD (p < 0.01). In all patients,
      the change in CBF after taking antihypertensive drugs was significantly inversely
      associated with baseline CBF (p < 0.01). Changes in regional CBF, measured by
      asymmetry scores, were significantly greater in patients with CAOD than in those
      without CAOD (p < 0.05). CONCLUSIONS: Elderly patients with occlusive
      extracranial cerebrovascular disease are at risk of drug-induced changes in both
      mean and regional CBF, and may benefit from a CBF assessment before being
      prescribed antihypertensive therapy.

PMID- 8570429
TI  - Inappropriate vancomycin prescribing based on criteria from the Centers for
      Disease Control and Prevention.
AB  - Increasing reports of vancomycin resistance have raised concerns about the future
      effectiveness of this drug in treatment of critically ill patients with gram
      positive infections. Due to these concerns the Centers for Disease Control and
      Prevention (CDC) recently published criteria that delineate the prudent use of
      vancomycin. Using these criteria, we attempted to determine the appropriateness
      of vancomycin prescribing patterns at our institution. A retrospective chart
      review was performed for 135 hospitalized patients treated between May 1993 and
      April 1994. Inappropriate empiric vancomycin use was documented in 81 (60%) of
      these patients. When culture results were available, 28 (21%) patients
      inappropriately received the drug. Results of this study are similar to those of
      other studies of vancomycin use in hospitals based on non-CDC criteria. If CDC
      criteria are to have a positive impact on physicians' vancomycin prescribing
      patterns, significant educational efforts will be required.

PMID- 8570430
TI  - International pharmacy.
AB  - Several worldwide initiatives involve pharmacy education and practice; however,
      the International Pharmaceutical Federation is the only worldwide pharmacy
      organization currently in existence. This is the first report of the good
      pharmacy practice initiative published in the United States. We hope that it will
      stimulate interest in international pharmacy.

PMID- 8570431
TI  - Analysis of pain management in critically ill patients.
AB  - We analyzed the adequacy of pain control for 17 trauma patients during the
      initial part of their stay in the intensive care unit, and assessed reasons for
      inadequate analgesia, if it occurred. Patients, and physicians, and nurses were
      interviewed. A verbal pain intensity scale was used to determine whether patients
      received adequate analgesia. Patients were asked if the pain hindered their
      activities, and whether they requested pain medication from their caregivers.
      Caregivers were questioned whether patients received adequate analgesia.
      Prescribed morphine regimens and the amount of narcotic administered were
      analyzed. Twenty-seven percent of patients rated pain intensity as moderate and
      47% as severe. Ninety-five percent of housestaff and 81% of nurses reported the
      patients received adequate pain control. Forty-seven percent of the patients who
      had moderate or severe pain asked their physician for more pain medication, and
      65% asked the nurse. Thirteen residents did not order a larger dose of morphine
      due to concern about respiratory depression or hypotension. Morphine dosages
      ranged from 1-8 mg intravenously every 1-2 hours as necessary. Nurses
      administered less than the maximum amount ordered 58% of the time. The mean
      dosing interval was 2.3 hours. Barriers to adequate pain management were
      disparity in the perception of pain between patients and caregivers; patients not
      requesting more analgesia despite despite the presence of moderate to severe
      pain; and physician and nurse concerns about patients' adverse physiologic
      response to increased dosages.

PMID- 8570433
TI  - The development of clinical practice guidelines for treatment of peptic acid
      diseases in a VA ambulatory care clinic.
AB  - The costly treatment of peptic acid diseases at a Veterans Affairs ambulatory
      care clinic prompted the development of clinical practice guidelines (CPGs) for
      the disorders. A committee consisting of a clinical pharmacist, the chiefs of
      ambulatory care and medicine, and a gastroenterologist guided the process. A
      consensus-style conference format involving medical staff and residents,
      pharmacists, and other health providers was chosen to develop the CPGs. Before
      the conference each participant received a list of key issues and literature on
      practice guidelines, and on peptic acid diseases and their treatment. At the
      conference the participants were divided into four groups; each group discussed
      specific key issues using a modified nominal group process. Recommendations from
      each group were made to the entire conference. Final recommendations were
      compiled into what was adopted and readily received as the CPGs for the
      institution.

PMID- 8570432
TI  - Quality of life in patients with metastatic colorectal cancer receiving
      chemotherapy: a randomized, double-blind trial comparing 5-FU versus 5-FU with
      leucovorin.
AB  - We compared health-related quality of life (HQL) measures in 210 patients with
      metastatic colorectal cancer who were receiving equitoxic regimens of weekly 5
      fluorouracil (5-FU) plus leucovorin (LV) or 5-FU alone in a multicenter, placebo
      controlled, double-blind, randomized trial. The HQL was assessed during the first
      120 days of treatment by the patient-generated functional living index-cancer
      (FLIC) questionnaire. Also assessed were clinician-generated measures to evaluate
      physical functioning and suffering: Karnofsky performance status (KPS), body
      weight, disease symptoms, and hospitalization. No significant difference was
      detected between treatment groups in HQL or in any measurement of efficacy or
      toxicity. The number of patients hospitalized was similar in both groups, 35
      patients receiving 5-FU-LV, 32 receiving 5-FU-placebo, but those receiving 5-FU
      LV were hospitalized longer (450 vs 315 total days). The KPS improved or
      stabilized in 23% and 37% of patients, respectively. Overall, FLIC scores
      significantly improved in 27% or remained stable in 62% of all patients; disease
      symptoms improved in 19-49%; a weight increase of 2 kg or more occurred in 27%. A
      change in FLIC was not associated with tumor response or improvement in pain, but
      a decline in FLIC was associated with improved survival. An improvement in KPS or
      weight was associated with tumor response and strongly correlated with survival.
      Improvement of pain was associated with a stable or increase in weight, and
      worsening of pain correlated with lack of tumor response.

PMID- 8570434
TI  - A community-based clinical pharmacy teaching, research, and service program in
      Zimbabwe.
AB  - In an effort to optimize limited resources, a community-based clinical pharmacy
      program was initiated to promote service, teaching, and research. This program
      sponsored the recruitment of pharmacy personnel to carry out distributive and
      clinical functions. This service enabled the development of new clinical
      attachment sites for pharmacy students. Students on these attachments carried out
      supervised projects that enhanced their learning while providing essential
      services to the community. This program resulted in the enhancement of stock
      levels of drugs and medical equipment, improvement in the drug budget through on
      site manufacturing and proper stock management, and the creation of a favorable
      working partnership with other health professionals as well as the community. A
      number of research projects were initiated and completed, and a teaching program
      was established. This program demonstrated that integration of the triple
      functions of clinical pharmacy service, teaching, and research is feasible in a
      rural setting and can achieve goals that are mutually beneficial to all facets of
      the pharmacy profession.

PMID- 8570435
TI  - Charcoal hemoperfusion for theophylline overdose: case report and proposal for
      predicting treatment time.
AB  - Charcoal hemoperfusion is effective in the treatment of theophylline overdose.
      Estimation of the time required for charcoal hemoperfusion has been based on
      personal experience and judgment. We used pharmacokinetic data from a patient and
      from case reports to generate a formula for predicting treatment time.
      Pharmacokinetic parameters were calculated using model-independent analysis of
      concentration-time curves from two treatments of charcoal hemoperfusion. These
      values were compared with published data and incorporated into a formula that was
      derived from the elimination rate constant to estimate treatment time of charcoal
      hemoperfusion: Time (min) = (ln conci-ln concd)/0.0057, where the concentration
      of theophylline is in mumol/L. The formula may be valid in patients in whom the
      serum theophylline concentration is less than or equal to 516 mumol/L or 92 mg/L.
      It may be used as a guide to estimate the length of charcoal hemoperfusion in the
      treatment of theophylline toxicity. Its validation requires implementation and
      evaluation in future cases.

PMID- 8570436
TI  - Analysis of various creatinine clearance formulas in predicting gentamicin
      elimination in patients with low serum creatinine.
AB  - Predicted gentamicin elimination rate constants (kelS) using creatinine clearance
      (Clcr) estimates from seven equations were compared with kelS calculated from
      steady-state serum gentamicin concentrations in 186 hospitalized patients. In
      predicting kel, the equations varied significantly in precision (mean absolute
      percentage error), and were particularly imprecise among patients with serum
      creatinine values of 71 mumol/L or less. Significant differences in bias (mean
      prediction error) were also observed. All equations using serum creatinine as an
      element showed improved precision, and most showed reduced bias when a minimum
      value of 71 mumol/L was used. The Cockcroft-Gault normalized to 72 kg and the
      Hull equations are among the simplest to calculate and, when using a minimum
      serum creatinine of 71 mumol/L, had significantly greater precision and less bias
      than several of the equations. We recommend one of these two methods for
      predicting gentamicin kel in patients with low serum creatinine values.

PMID- 8570437
TI  - The emerging role of valproate in bipolar disorder and other psychiatric
      disorders.
AB  - Although valproate, a simple branched-chain fatty acid, is generally considered
      to be an antiepileptic agent, a large literature dating back to 1966 describes
      its use in primary psychiatric disorders. The significant role that gamma
      aminobutyric acid plays in mood provided the rationale to examine valproate in
      this regard. Numerous uncontrolled as well as placebo- and lithium-controlled
      studies verified the drug's efficacy in the short-term management of bipolar and
      schizoaffective disorders. The response appears to be independent of response to
      traditional therapies such as lithium, neuroleptics, and carbamazepine, and may
      be maintained for extended periods of time. Valproate should be considered not
      only in patients with mood disorders who are intolerant of or nonresponsive to
      traditional therapies, but also in those with rapid cycling,
      electroencephalographic abnormalities, head trauma antedating the onset of
      psychiatric illness, or any other factor suggesting an organic component.
      Preliminary uncontrolled studies suggest that the drug may also eventually play a
      role in the management of panic disorder and behavioral dyscontrol (agitation,
      aggression, temper outbursts). Its adverse event profile is well known from years
      of experience in the management of epilepsy and does not appear to be altered in
      the presence of psychiatric disorders. Similarly, the drug-drug interaction
      potential of valproate is reasonably well known, although further research into
      interactions with psychotropic agents is warranted.

PMID- 8570438
TI  - Natural antioxidants for the prevention of atherosclerosis.
AB  - Hypercholesterolemia, cigarette smoking, hypertension, and obesity are known
      contributing risk factors for the development of atherosclerotic coronary artery
      disease (CAD). However, they account for only half of all cases of CAD, and the
      complete pathologic process underlying atherosclerosis remains unknown. Growing
      evidence suggests that oxidative modification of low-density lipoprotein (LDL)
      may be of particular importance in the pathogenesis. Oxidized LDL exhibits
      proatherogenic effects. Therefore, current research has focused on inhibiting the
      oxidation of LDL as a means of inhibiting the atherosclerotic process. One such
      approach is to enhance the endogenous antioxidant defense systems within the LDL
      particle with lipophilic antioxidants such as alpha-tocopherol and beta-carotene,
      or by supplementing the aqueous-phase antioxidant capacity with ascorbic acid.
      Observational data suggest a protective effect of antioxidant supplementation on
      the incidence of CAD; however, specific doses cannot be recommended since the
      data are inconclusive.

PMID- 8570439
TI  - Effect of high-dose sodium bicarbonate on the vasopressor effects of epinephrine
      during cardiopulmonary resuscitation.
AB  - We attempted to determine the effect of extreme alkalemia induced by highdose
      sodium bicarbonate on the vasopressor effects of epinephrine during
      cardiopulmonary resuscitation (CPR). Subjects in this randomized, blinded study
      performed in a controlled laboratory environment were 12 mongrel dogs that had
      had a previous episode of CPR. Each dog underwent 3 minutes of ventricular
      fibrillation (VF) followed by 7 minutes of closed-chest CPR. Animals were
      assigned to receive either sodium bicarbonate 3 mEq/kg and epinephrine 0.1 mg/kg,
      or normal saline 3 ml/kg and epinephrine 0.1 mg/kg. The sodium bicarbonate or
      normal saline was infused over 2 minutes beginning at 4 minutes of VF (1 min of
      CPR) followed by bolus epinephrine. Arterial pH in the sodium bicarbonate group
      was significantly higher at each sampling point (7.7 +/- 0.1 vs 7.29 +/- 0.06 at
      1 min after drug, p < 0.001). However, there were no statistically or clinically
      significant differences in coronary perfusion pressure between the groups at any
      time: 29 +/- 13 versus 32 +/- 21 mm Hg 1 minute, and 22 +/- 12 versus 26 +/- 19
      mm Hg 4 minutes after epinephrine for sodium bicarbonate and normal saline,
      respectively (p > 0.7). Increased arterial pH (alkalemia) induced by high-dose
      sodium bicarbonate administration did not improve the vasopressor effects of
      epinephrine during CPR in this canine model. These results suggest the limited
      value of administering sodium bicarbonate during CPR to improve the
      responsiveness to epinephrine.

PMID- 8570440
TI  - Severe withdrawal syndrome possibly associated with cessation of a midazolam and
      fentanyl infusion.
AB  - A 40-month-old child was sedated with a fentanyl and midazolam infusion for 7
      days. After the drugs were discontinued he became unresponsive and globally
      aphasic, and had marked thrombocytosis. He was hospitalized for 4 weeks, during
      which time his motor and cognitive status slowly improved, and had almost
      returned to baseline at time of discharge. Severe neurologic abnormalities have
      been reported with midazolam and fentanyl, administered separately or together,
      and seem to be a consequence of a withdrawal syndrome. Of interest, this patient
      had a reactive thrombocytosis at the time of onset of the withdrawal syndrome,
      and his decreased platelet count coincided with the return to normal cognitive
      and motor status. Based on this experience and other reports, we believe
      midazolam-fentanyl combination should be administered with caution.

PMID- 8570441
TI  - Nabumetone-associated interstitial nephritis.
AB  - An 84-year-old woman was admitted to the hospital for progressive edema and
      decreased urine output. She had been taking nabumetone for 6 months, but had
      discontinued the agent 2 weeks before admission due to progressive edema. On
      admission she had 2-3+ pitting edema. Her serum electrolytes were sodium 122
      mEq/L, potassium 5.9 mEq/L, chloride 93 mEq/L, and carbon dioxide 19 mEq/L. A
      urinalysis was significant for protein 3061 mg/dl, ketones 15 mg/dl, blood 2+,
      leukocytes 26-50/high-power field, and a protein:creatinine ratio 24.9. The serum
      creatinine and blood urea nitrogen concentrations were 2.7 mg/dl and 70 mg/dl,
      respectively. Throughout hospitalization the patient underwent aggressive
      diuresis. She developed congestive heart failure, and hemodialysis was initiated.
      A renal biopsy specimen on hospital day 9 showed tubular damage with minimal
      glomerular changes consistent with a diagnosis of nonsteroidal agent-induced
      nephropathy. On day 13, a 24-hour urine collection had a protein excretion of
      3151 mg. Although the patient recovered from her renal failure (creatinine
      clearance 43 ml/min), the nephrotic syndrome persisted (13 g protein/day). The
      patient developed infectious complications and died on hospital day 32.

PMID- 8570442
TI  - Evaluation of plasmapheresis on the removal of tobramycin.
AB  - A 26-year-old man with thrombotic thrombocytopenic purpura resulting in
      respiratory and renal failure was treated with plasmapheresis (PP). Coexisting
      pulmonary infiltrates were empirically treated as pneumonia with various
      antibiotics, including vancomycin and tobramycin. The half-life of tobramycin was
      6.93 hours. During PP the half-life of tobramycin decreased to 4.47 hours as
      determined by three random levels. The fraction eliminated due to PP was 35.5%
      and the fraction cleared by PP was 10.9%. We conclude that PP contributed
      significantly to the total clearance of tobramycin. The need for supplemental
      doses must be evaluated in each patient based on post-PP serum concentrations.

PMID- 8570443
TI  - Cost comparison of beta 2-agonist bronchodilators used in the treatment of
      asthma.
AB  - Because of increases in the morbidity and mortality associated with asthma,
      coupled with shrinking health care resources, the costs associated with therapy
      with beta 2-agonists in metered-dose inhalers (MDIs), the most frequently used
      class of therapeutic agents, were examined. Recent recommendations suggested a
      change in drug therapy for asthma, away from theophylline and toward patient
      administered MDIs containing beta 2-agonists or corticosteroids. These
      recommendations are expected ultimately to reduce overall costs by decreasing
      morbidity due to asthma and by reducing hospital services. Furthermore,
      differences exist among the various beta 2-agonists. For example, for patients
      treated with albuterol inhalers, total asthma drug costs, the costs of additional
      asthma drugs, and hospital costs were lower than those for patients treated with
      metaproterenol inhalers, despite the higher acquisition cost of albuterol. Using
      the maximum recommended number of daily inhalations and standardized pricing
      data, the daily costs of nine individual beta 2-agonists in MDIs were calculated.
      These varied from $0.61 for albuterol to $1.28 for pirbuterol, but would be lower
      for patients who required fewer daily inhalations on an as-needed basis. In
      addition, agents that can be dosed as needed (i.e., albuterol) are likely to be
      more cost-effective choices for formularies than more expensive new
      bronchodilators such as salmeterol, which must be given twice/day on a regular
      basis.

PMID- 8570444
TI  - Vancomycin prescribing in the era of vancomycin-resistant enterococci.

PMID- 8570445
TI  - Vancomycin-resistant enterococci.

PMID- 8570446
TI  - Cerebrospinal fluid shunt complications: an emergency medicine perspective.
AB  - Shunt malfunction and shunt infections are the most significant complications
      associated with cerebrospinal fluid shunts. Most cases of shunt infection are due
      to S. epidermidis or S. aureus. Seventy percent of all shunt infections present
      within two months of the shunt surgery. The most common factor associated with
      shunt infection is age under three months. Even fever may not be a consistent
      sign of shunt infection. A high index of suspicion for shunt infection or
      malfunction must be maintained when evaluating the patient with a cerebrospinal
      fluid shunt. There are many types of shunt systems in use today. An understanding
      of current shunt systems and their associated problems should allow physicians to
      promptly diagnose and initiate treatment for patients with cerebrospinal fluid
      shunts. Prompt neurosurgical consultation is mandatory whenever shunt malfunction
      or infection is suspected.

PMID- 8570447
TI  - Circumferential pressure as a rapid method to assess intraosseous needle
      placement.
AB  - This study was done to determine whether the application of circumferential
      pressure about an intraosseous (IO) site can be used as a rapid method to detect
      incorrect placement of an IO needle. We used a prospective, randomized,
      controlled canine tibial IO model. According to random assignment, IO needles
      were placed either intramedullary (correct placement) or extramedullary
      (incorrect placement) in the anteromedial tibias of 12 euthanized mongrel dogs.
      Neonatal blood pressure cuffs were placed contiguously above and below the IO
      needles. One-liter bags of solution were connected to the IO needles via blood
      tubing. The gravity-dependent rate of flow at each site was measured with and
      without the blood pressure cuffs inflated to 120 mmHg. Eleven IO needles were
      correctly placed and 13 were incorrectly placed. Following inflation of the blood
      pressure cuffs, the mean percent decrease in flow was 48% for the correctly
      placed IO needles, and 95% for the incorrectly placed IO needles. A two-way
      repeated measure of analysis of variance was significant between groups (P =
      0.006), and a significant interaction was found between groups and flow rates
      over time (P = 0.043). We conclude that circumferential pressure about an IO
      infusion site can be used as a rapid method to detect incorrect placement of the
      IO needle.

PMID- 8570448
TI  - Can emergency physicians correlate between vehicle damage and velocity change?
AB  - The objective to this study was to examine the ability of emergency physicians to
      correlate between vehicle damage and velocity change. Participants were five
      emergency medicine physicians at the Emergency Department, Loyola University
      Medical Center, Maywood, IL. Ten slides of passenger cars crashed at speeds
      between 22 and 70 mph by the Insurance Institute for Highway Safety were shown to
      study participants. Study subjects were asked to estimate vehicular velocity
      based on the visible damage. Only 23 (46%) of the estimates were within 10 mph of
      the vehicular speed at the time of the crash. The average error was 14.5 mph
      (range: -20 to +45 mph). Vehicular velocity was overestimated in 70% of the
      appraisals. We conclude that the ability of emergency physicians to correlate
      between vehicle damage and velocity change is limited. Underestimation of
      vehicular damage associated with low velocity accidents may result in
      misdiagnosis of severe injuries in motor vehicle accident victims.

PMID- 8570449
TI  - Bacteremia and meningitis among infants with urinary tract infections.
AB  - A retrospective analysis of 354 patients < or = 2 years of age with urinary tract
      infections (UTIs) was performed to characterize patients with bacteremia or
      meningitis and to identify any objective predictors of these complications.
      Thirty-three patients with bacteremia were identified. Blood culture isolates
      included Escherichia coli (25), Staphylococcus aureus (4), enterococcus (1),
      group B Streptococcus (2), and Enterobacter (1). Besides one patient with group B
      Streptococcus bacteremia at 1.5 months of age, all bacteremias after one month of
      age were with E. coli. Bacteremia was limited to those < 6 months old and
      inversely related to age (R = 0.24, P = 0.0008). Grouped by age, the incidence of
      bacteremia was 21% for 0 < or = 1 month, 13% for 1.1-2.0 months, 4% for 2.1-3.0
      months, and 8% for 3.1-6.0 months. Mean white blood cell count, initial
      temperature, initial serum bicarbonate, and erythrocyte sedimentation rate were
      not statistically significant between bacteremic (B) and nonbacteremic (NB)
      patients. Statistically significant differences were noted for percentage of
      bands (6.2% [NB] vs. 12.3% [B] P < 0.001), total band count (1048 [NB] vs. 2252
      [B] P < 0.001), and band-neutrophil ratio (0.16 [NB] vs. 0.36 [B] P = 0.01);
      however, no practical value for any of these measures would reliably discriminate
      between bacteremic and nonbacteremic patients. Four patients, all neonates, had
      meningitis; too few patients with meningitis were identified for analysis. In
      summary, bacteremia with UTIs was observed to be inversely related to age and
      limited to patients less than six months of age. No objective parameters were
      identified to distinguish patients with bacteremia at the time of presentation.

PMID- 8570450
TI  - Failure of technetium-99m hexamethylpropylene amine oxime leukocyte scintigraphy
      in the evaluation of children with suspected appendicitis.
AB  - To determine the accuracy and reliability of a labeled leukocyte imaging
      technique in the early diagnosis of pediatric appendicitis, we prospectively
      studied patients presenting to the pediatric emergency department with abdominal
      pain suggestive of appendicitis. Patients scheduled for urgent laparotomy were
      excluded, as were postmenarchal females. Blinded interpretations by two
      independent radiologists were compared with surgical findings, if managed
      operatively, or with discharge diagnoses and three week follow-up, if managed
      medically. Twenty-three children underwent technetium-99m hexamethylpropylene
      amine oxime (HMPAO) leukocyte scintigraphy. Seven had pathologically proven
      appendicitis, with false negative interpretations made in three and five cases by
      the two radiologists. Sixteen patients had prompt resolution of symptoms;
      however, scintigraphic abnormalities were identified in 10 and seven cases by the
      two radiologists. Resulting sensitivity, depending on the individual reader,
      ranged from 29 to 57%, with specificity 38 to 56%, positive predictive value 22
      to 29%, negative predictive value 64 to 67%, and accuracy 43 to 48%. Interrater
      reliability for agreement on the scintigraphic diagnosis of appendicitis was poor
      (kappa = 0.38). Technetium-99m HMPAO leukocyte scintigraphy was neither accurate
      nor reliable as a diagnostic tool in a subgroup of pediatric patients with an
      initial clinical presentation equivocal for appendicitis. This finding
      contradicts previously published experience using similar scintigraphic
      techniques.

PMID- 8570451
TI  - Traumatic hip dislocation in a young child: a case report and discussion.

PMID- 8570452
TI  - Methemoglobinemia in an infant: case report and review of the literature.

PMID- 8570453
TI  - Retropharyngeal air accumulation as a complication of pneumomediastinum and a
      cause of airway obstruction in asthma.

PMID- 8570454
TI  - Varicocele as a presenting feature of Wilms' tumor.

PMID- 8570455
TI  - Magill forceps: a vital forceps.
AB  - Foreign body aspiration is not an uncommon problem in infants and toddlers, and
      should be considered as a serious and sometimes fatal condition. We report three
      cases of foreign body aspiration which were located below the vocal cords,
      causing a nearly complete airway obstruction with severe respiratory distress. In
      all cases they were successfully removed in the emergency department using a
      laryngoscope and Magill forceps. It is important for physicians who take care of
      children in emergency department to know the management of these life-threatening
      situations. Knowledge of pediatric advanced life support measures with airway
      management and proper training in laryngoscope and Magill forceps management can
      save lives in many children.

PMID- 8570456
TI  - Pott's disease: an old disease reappears in the pediatric emergency department.

PMID- 8570457
TI  - Case 04-1995: a neonate with seizures.

PMID- 8570458
TI  - Dog bites.

PMID- 8570459
TI  - Posttraumatic elbow swelling and inflammation.

PMID- 8570460
TI  - Patient-controlled analgesic infusion pumps.

PMID- 8570462
TI  - Umbilical cord teaching.

PMID- 8570461
TI  - Central venous catheters in the emergency department: access, utilization, and
      problem solving.

PMID- 8570463
TI  - Fumes from the spleen.

PMID- 8570464
TI  - Smoking in pregnancy as a risk factor for long-term mortality in the offspring.
AB  - This study addresses the question of whether maternal smoking is related to
      postneonatal mortality and which are the contributing causes of death. Mortality
      of births in Sweden between 1 January 1983 and 31 December 1989 (n = 714,389)
      registered in the Medical Birth Registry was followed until 31 December 1990. The
      registry carries information on maternal smoking habits in early pregnancy. The
      Mantel-Haenszel procedure was used to control for confounding effects of maternal
      age, parity and year of birth: relative risks (95% confidence interval)
      associated with smoking were: 1.24 (1.17-1.31) for fetal death, 1.08 (1.01-1.16)
      for early neonatal death, 1.22 (1.08-1.39) for late neonatal death, 1.31 (1.23
      1.41) for postneonatal mortality during the first year, and for the period
      between 1 and 8 years of age it was 1.19 (1.06-1.32). When birthweight was
      controlled for, the increased relative risk for postneonatal mortality during the
      first year disappeared. Mortality between 1 and 8 years still showed an elevated
      risk of 1.43 (1.00-2.06). In order to control for confounding by social factors,
      1986 births were linked to data from the 1985 Swedish census. The measure used
      was the socio-economic index (SEI), which reflects the parental education level.
      When maternal, paternal or family SEI was controlled for, late neonatal death was
      not significantly related to maternal smoking, but postneonatal death still
      showed a significantly increased relative risk of about 1.35. Four causes of
      death based on International Classification of Diseases (ICD) 8 and 9 were
      significantly related to maternal smoking: sudden infant death syndrome, injuries
      and poisoning, perinatal causes and infections.

PMID- 8570465
TI  - The intergenerational relationship between mother's birthweight, infant
      birthweight and infant mortality in black and white mothers.
AB  - The relationship between the birthweight of white and black mothers and the
      outcomes of their infants were examined using the 1988 National Maternal and
      Infant Health Survey. White and black women who were low birthweight themselves
      were at increased risk of delivering very low birthweight (VLBW), moderately low
      birthweight (MLBW), extremely preterm and small size for gestational age (SGA)
      infants. Adjustment for the confounding effects of prepregnant weight and height
      reduced the risks of all these outcomes slightly, and more substantially reduced
      the maternal birthweight associated risk of moderately low birthweight among
      white mothers. There was little effect of maternal birthweight on infant
      birthweight-specific infant mortality in white mothers; however, black mothers
      who weighed less than 4 lbs at birth were at significantly increased risk of
      delivering a normal birthweight infant who subsequently died. Although the risks
      for the various outcomes associated with low maternal birthweight were not
      consistently higher in black mothers compared with white mothers, adjustment for
      prepregnant weight and height had a greater effect in white mothers than in black
      mothers. We suggest that interventions to reduce the risks for adverse pregnancy
      outcomes associated with low maternal birthweight should attempt to optimise
      prepregnant weight and foster child health and growth.

PMID- 8570466
TI  - Pathology review of sudden and unexpected death in aboriginal and non-aboriginal
      infants.
AB  - Previous research showed that the sudden infant death syndrome (SIDS) rate for
      Aboriginal infants significantly increased during the 1980s in Western Australia
      (WA) and raised the possibility of a diagnostic transfer of Aboriginal infant
      deaths from other causes to SIDS over this period. Here, therefore we review the
      pathology of SIDS and other sudden and unexpected deaths in infancy (SUDI) for
      Aboriginal and non-Aboriginal infants in WA between 1980 and 1988. The aim was to
      investigate whether there had been differences in the diagnosis and/or
      classification of SIDS according to whether the infants were Aboriginal or non
      Aboriginal. The study population comprised: (1) all Aboriginal cases of SIDS and
      other SUDI between 1980 and 1988, and (2) corresponding random samples of non
      Aboriginal cases. A two-stage process was employed for the review. First,
      histology slides were reviewed for each case where the aboriginality of the
      infant was Aboriginal and the original cause of death were unknown to the
      pathologists. Second, all paper records (i.e. death scene investigations,
      laboratory tests and medical reports) except for the original cause of death
      information were reviewed by the pathologists. The results showed that there was
      excellent agreement between the final review diagnosis and the original diagnosis
      for both Aboriginal and non-Aboriginal SUDI. Thus, there was no evidence for a
      diagnostic shift among Aboriginal infant deaths and the review supported the
      observed increase in the SIDS rate for Aboriginal infants.

PMID- 8570467
TI  - Which birthweight groups contributed most to the overall reduction in the
      neonatal mortality rate in the United States from 1960 to 1986?
AB  - We determined the relative contributions of individual birthweight groups to the
      reduction in neonatal mortality rate (NMR) of US singleton livebirths from 1960
      to 1986, the period during which neonatal intensive care was introduced and
      became established. Changes in the NMR for each race (non-white/white) and
      birthweight group were assessed in terms of three components of NMR (1)
      birthweight-specific neonatal mortality rate (BWS-NMR), (2) birthweight
      distribution, and (3) the interaction resulting from simultaneous changes in BWS
      NMR and birthweight distribution. Overall, NMR decreased from 16.7 per 1000
      livebirths in 1960 to 5.5 per 1000 livebirths in 1986. This reduction was
      achieved mainly by improvements in the BWS-NMRs of all birthweight groups.
      Neonates who weighted > 1.5 kg at birth were the major contributors to the
      overall reduction in the NMR; approximately two-thirds of total reduction in NMR
      between 1960 and 1980 and 52.6% of the total reduction between 1980 and 1986
      occurred in the > 1.5 kg birthweight groups. Our study demonstrates that with the
      introduction of neonatal intensive care, survival of infants with birthweights >
      1.5 kg improved markedly and that this improvement accounted for most of the
      decline in the neonatal mortality rate in the United States from 1960 to 1986.
      Therefore, in measuring the effectiveness of neonatal intensive care, the
      assessment should include not only very low birthweight (< 1.5 kg) but all
      birthweight groups.

PMID- 8570468
TI  - The association between small size for gestational age and perinatal and neonatal
      death in a UK Regional Health Authority.
AB  - Confidential enquiry into stillbirth and death in infancy is a health service
      requirement in England, Wales and Northern Ireland. A confidential review of
      perinatal death has been conducted in South-East Thames Region since 1988. Data
      collected for this review are analysed here. Among the 1662 singleton deaths in
      the enquiry from 1988 to 1991, 530 (32%) babies were small for gestational age
      (SGA < 10th centile): 338 of these (64%) were < 3rd centile and the remainder
      were between 3rd-10th centile. Small size for gestational age was significantly
      associated with a previous SGA baby (P = 0.02), proteinuric hypertension (P =
      0.001) and increased placental-birthweight ratio (P = 0.008). Only 135 (25%) SGA
      fetuses were identified antenatally and multiple logistic regression showed that
      antenatal detection was independently related to proteinuric hypertension [odds
      ratio (OR) = 2.47, 95% confidence interval (CI) 1.47-4.17, P = 0.001) and to
      being < 3rd centile rather than 3rd-10th centile (OR = 3.16, 95% CI 1.96-5.10, P
      = 0.001). Although confidential enquiries have been criticised for a lack of
      objectivity the study indicates how data from such an enquiry can increase
      knowledge of events influencing peri- and neonatal outcome allowing strategies to
      be devised to effect change.

PMID- 8570469
TI  - Preterm birth and low birthweight among children of Swedish and immigrant women
      between 1978 and 1990.
AB  - The aim of the study was to estimate the occurrence of low birthweight (LBW) and
      preterm birth among immigrant and Swedish women in Sweden. Eligible for analysis
      were all 1,270,407 singleton births in Sweden between 1978 and 1990 to mothers
      aged between 15 and 44 years, whose own country of birth was known. The mothers
      of the children were born in Sweden (88.2%), or had immigrated from Finland
      (4.4%), other Scandinavian countries (1.2%), Western Europe or North America
      (1.3%), Eastern Europe (1.8%), the Middle East and North Africa (1.7%), Central
      and South America (0.6%), Asia and the Pacific Islands (0.6%), or Sub-Saharan
      Africa (0.2%). Multiple logistic regression was used to model LBW and preterm
      birth categorical outcomes. Each immigrant group was compared with the Swedish
      group. Odds ratios (ORs) for LBW were 1.13 (95% CI 1.04, 1.22) for Asia and the
      Pacific Islands, 1.21 (1.05, 1.38) for Sub-Saharan Africa and 0.89 (0.86-0.93)
      for Finland. Odds ratios for preterm birth were 1.15 (1.08-1.23) for immigrants
      from Asia and the Pacific Islands and 1.08 (1.04, 1.13) for immigrants from
      Eastern Europe. Remarkably small differences were found between immigrant women
      and native Swedish women.

PMID- 8570470
TI  - Low birthweight and the risk for mental retardation later in childhood.
AB  - Data from the population-based Metropolitan Atlanta Developmental Disabilities
      Study were used in a case-control study to assess the association between low
      birthweight and mental retardation (intelligence quotient < or = 70) among 10
      year-old children who were born in 1975 or 1976. Children with mental retardation
      were identified from existing records at multiple sources and control children
      were selected from public school rosters. Data on birthweight and other
      covariates (sex, birth order, maternal age, maternal race, maternal education and
      gestational age) came from birth certificates. We used multiple logistic
      regression modelling to obtain adjusted odds ratios for mental retardation, with
      normal birthweight children (those weighing > or = 2500 g) as the referent group.
      For low birthweight children as a whole, the odds ratio for mental retardation
      was 2.8 (95% CI 1.9-4.2). The risk was higher for very low birthweight (< 1500 g)
      children than for moderately low birthweight (1500-2499 g) children, and higher
      for severe mental retardation (intelligence quotient < 50) than for mild mental
      retardation (intelligence quotient 50-70). Adding gestational age to the models
      revealed that normal birthweight children who were born preterm also were at
      increased risk of having mental retardation at age 10 years.

PMID- 8570471
TI  - 10th Annual Current Concepts in Joint Replacement meeting. Proceedings. Orlando,
      Florida, December 1994.

PMID- 8570472
TI  - Joint arthroplasty: one step forward, two steps back.

PMID- 8570473
TI  - Osteolysis: a generic problem.

PMID- 8570474
TI  - The clinical significance of implant stiffness.

PMID- 8570475
TI  - Femoral component fixation in the 1990s. Which system? A selection rationale.

PMID- 8570476
TI  - Cemented arthroplasty: a long look back.

PMID- 8570477
TI  - Porous-coated fixation: a rite of passage.

PMID- 8570478
TI  - The lessons of acetabular component fixation.

PMID- 8570479
TI  - Cementless acetabular components: optimums and outcomes.

PMID- 8570480
TI  - The role of osteotomies in the 90's.

PMID- 8570481
TI  - Treatment of avascular necrosis in the young patient.

PMID- 8570482
TI  - Solution options: modular hip stem design.

PMID- 8570483
TI  - Solution options: unitized stem design.

PMID- 8570484
TI  - Diagnosis and management of the infected hip prosthesis.

PMID- 8570485
TI  - Blood management: facts and fictions.

PMID- 8570486
TI  - Thromboembolism after THR: prophylaxis and treatment.

PMID- 8570488
TI  - Failure mechanisms of hip arthroplasty.

PMID- 8570487
TI  - Changing transfusion practices in orthopedic surgery.

PMID- 8570489
TI  - Cementless revision for femoral failure.

PMID- 8570490
TI  - Cemented revision for femoral failure.

PMID- 8570491
TI  - Management of acetabular deficiency.

PMID- 8570492
TI  - Structural grafting of the acetabulum.

PMID- 8570493
TI  - Management of the structurally deficient femur in revision total hip replacement.

PMID- 8570494
TI  - The economic impact of infected joint arthroplasty.

PMID- 8570495
TI  - The economics of revision arthroplasty.

PMID- 8570496
TI  - Metal/metal articulating interfaces.
AB  - Polyethylene wear can be shown as a problem in long-term joint replacement. Metal
      on-metal bearing is solving this problem, as long-term clinical and experimental
      investigations demonstrate. To avoid the problem of high friction found in old
      series, a new Metasul called technique with a smaller diameter was invented.
      Intermediate results of Weber and our own data show promising outlook for a
      solution to the wear-induced problem in hip replacement.

PMID- 8570497
TI  - Polyethylene: a bridge too far.

PMID- 8570498
TI  - Precoat components: another look.

PMID- 8570500
TI  - Knee arthroplasty: then, now, and tomorrow.

PMID- 8570499
TI  - Hydroxyapatite: coating controversies.

PMID- 8570501
TI  - Isolated patellofemoral arthritis.

PMID- 8570502
TI  - Unicompartmental disease: solution options.

PMID- 8570503
TI  - Bi/tri-compartmental degenerative knee disease in the young patient.

PMID- 8570504
TI  - Controversial issues in knee arthroplasty.

PMID- 8570505
TI  - Mechanisms of knee implant failure.

PMID- 8570506
TI  - Extensor mechanism complications after total knee arthroplasty.

PMID- 8570507
TI  - Supracondylar fractures: all or nothing.

PMID- 8570508
TI  - Bone loss: prosthetic and augmentation method.

PMID- 8570509
TI  - Operative management of the infected knee.
AB  - We have six choices in selecting treatment for infected TKA. My preference is two
      stage revision arthroplasty combined with appropriate parenteral antibiotic
      therapy. This treatment provides a success rate of approximately 90% for cure of
      infection and good function in most instances.

PMID- 8570510
TI  - Revision TKA: is cement really necessary?

PMID- 8570511
TI  - Revision total knee arthroplasty: how much constraint is necessary?
AB  - The majority of revision total knee arthroplasties will achieve sufficient
      stability with a posterior stabilized design. However, when partial compromise of
      the medical collateral ligament is encountered, enhanced stability should be
      achieved with the use of a CCK device. Rarely, hinged designs will be necessary
      as salvage procedures for low demand patients. The principles of total knee
      arthroplasty stability, as in primary surgery, require an anatomic alignment of
      the extremity, proper alignment of the prosthetic components, and physiologic
      symmetry of the collateral ligaments in both flexion and extension to assure a
      successful result.

PMID- 8570512
TI  - Evolving technologies in knee instrumentation.

PMID- 8570513
TI  - Hip challenges: what would you do?

PMID- 8570514
TI  - Knee challenges: what would you do?

PMID- 8570515
TI  - Methodologies for pharmaceutical effectiveness and pharmacoeconomics research.

PMID- 8570516
TI  - Optimization of lyophilization conditions for recombinant human interleukin-2 by
      dried-state conformational analysis using Fourier-transform infrared
      spectroscopy.
AB  - PURPOSE: Examination of the dried-state conformation of interleukin-2 (IL-2) was
      used to determine the pH conditions and stabilizers that provide optimal storage
      stability for the lyophilized product. METHODS: Fourier-transform infrared
      spectroscopy and accelerated stability studies which examined solubility,
      aggregate formation, and covalent cross-linking were used. RESULTS: Varying the
      pH in the absence of excipients resulted in dramatic differences in the dried
      state conformation of IL-2. At pH 7, IL-2 unfolds extensively upon lyophilization
      while at pH below 5 it remains essentially native. Additional unfolding was
      observed upon incubation at elevated temperatures. A strong direct correlation
      between the retention of the native (aqueous) structure during freeze-drying and
      enhanced stability is demonstrated. IL-2 prepared at pH 5 is approximately an
      order of magnitude more stable than at pH 7 with regard to formation of soluble
      and insoluble aggregates. A similar pH profile was observed in the presence of
      excipients, although the excipients alter the overall stability profile.
      Additional accelerated stability studies examined the stabilizers necessary for
      optimal stability. CONCLUSIONS: Excipients with the capacity to substitute for
      water upon dehydration better preserve the native structure resulting in enhanced
      stability. Those that have high glass transition temperatures provide the highest
      level of stability during storage, although they do not prevent dehydration
      induced unfolding.

PMID- 8570517
TI  - Vial lyophilization: calculations on rate limitation during primary drying.
AB  - PURPOSE: The aim of this study was to assess the rate limiting factors in the
      sublimation phase of freeze drying and to propose a simple model on the basis of
      these rate limitations. METHODS: A programmable freeze dryer was used. The load
      consisted of vials of varying size and various contents. To increase heat
      transfer, conductive paste was applied while the resistance toward mass transport
      was varied by using different restrictive capillaries. RESULTS: It was found that
      heat transfer limits the rate of sublimation. Presence of the commonly used
      excipient mannitol did not have a consequence on the rate of sublimation. The
      same applied for the restrictions towards mass transport. It was found that there
      exists not only a barrier against heat transport under the vial, but also between
      the glass wall and the frozen solution. CONCLUSIONS: From the results, a set of
      equations is proposed that enables to predict optimum sublimation conditions. For
      the pharmaceutical technologist this can serve as a simple and useful tool to
      derive a suitable freeze drying program.

PMID- 8570518
TI  - Computer simulation of tablet motion in coating drum.
AB  - PURPOSE: The purpose is to develop a new method of finding optimal conditions in
      tablet coating operations with the use of computer simulation. METHODS:
      DEM(Discrete Element Method), which calculates trajectories of individual tablets
      by numerically integrating Newton's equations of motion, was used in this
      simulation. RESULTS: The effects of tablet size, tablet loading, rotation speed
      on mean surface time, circulation time, and surface time deviation agree
      qualitatively with experimental results by other workers. CONCLUSIONS: It is
      found that DEM is a useful method of predicting tablet motion in a coating drum.

PMID- 8570519
TI  - Preparation of controlled-release coevaporates of dipyridamole by loading neutral
      pellets in a fluidized-bed coating system.
AB  - PURPOSE: The purpose of this study was to demonstrate that it is possible to
      prepare controlled-release drug-polymer coevaporates on an industrial scale,
      omitting the recovery problems and the milling and sieving processes encountered
      when coevaporates are prepared by the conventional solvent-evaporation technique.
      METHODS: Controlled-release coevaporates were prepared by spraying organic
      solutions of dipyridamole-Eudragit blends onto neutral pellets using the
      fluidized-bed coating method. Enteric acrylic polymers Eudragit L100-55, L, and S
      were used as dispersing agents and drug/polymer ratio 2:8 was selected for all
      formulations. Polarized light microscopy, X-ray diffraction spectroscopy, and
      differential scanning calorimetry were used to determine whether the drug was
      amorphous or crystalline in the coating films. Moreover, in vitro dissolution
      tests were performed on the dipyridamole coated pellets in test media simulating
      the pH variations in the GI tract and the results were compared to the release
      data obtained from coevaporates prepared by the conventional solvent-evaporation
      method. RESULTS: All the results clearly indicate that dipyridamole is amorphous
      in the coating films deposited on neutral pellets as well as in coevaporate
      particles obtained by the conventional solvent-evaporation method. When the
      release patterns of the dipyridamole coated pellets are compared to those of the
      drug coevaporate particles prepared with the same enteric acrylic polymers, the
      results show similar dissolution trends. CONCLUSIONS: The results obtained
      indicate that pelletization can be considered as a method of choice for pilot
      plant and/or full-scale production of controlled-release dosage forms based on
      the formation of amorphous solid dispersions.

PMID- 8570520
TI  - Physicochemical characterization of parenteral lipid emulsion: influence of
      cosurfactants on flocculation and coalescence.
AB  - PURPOSE: The stability of lipid emulsions (LE) containing various cosurfactants
      (oleic acid, cholesterol, Tween 80, or HCO-60) was evaluated using the maximum
      total interaction energy, Vtmax and the energy barrier for coalescence, W.
      METHODS: The Vtmax and W were calculated from the zeta potential and the rate of
      increase in LE particle size, respectively. RESULTS: The Vtmax and W of LE
      containing the oleic acid were 0.598 x 10(-19) J and 3.03 x 10(-19) J,
      respectively, while those of LE without the cosurfactant were 0.141 x 10(-19) J
      and 1.36 x 10(-19) J. CONCLUSIONS: These findings suggest that oleic acid
      prevents the flocculation and coalescence of LE. The Vtmax and W of LE containing
      the cholesterol were 0.435 x 10(-19) J and 0.63 x 10(-19) J, respectively,
      suggesting that the cholesterol prevents the flocculation of LE but does not
      affect the coalescence. Analysis of the stability of LE was performed by the
      separate considerations of the flocculation and coalescence.

PMID- 8570521
TI  - Hydrophobic contribution constants of amino acid residues to the hydrophobicities
      of oligopeptides.
AB  - PURPOSE: The main purpose of this study is to explore the additive-constitutive
      nature of common amino acids in their contribution to the partition coefficients
      of small peptides. METHODS: The Log P values and other physico-chemical
      parameters of the peptides studied are taken from the literature. The frequency
      of appearance (ni) of each individual amino acid is calculated as the number of
      the amino acids in a given peptide. RESULTS: The partition coefficients (Log
      P(oct./buff.) at pH 7) of 87 N-acetyl-peptide-amides have been correlated with
      the frequency of appearance of amino acids. From the correlation obtained, the de
      novo hydrophobic contribution constants of 19 amino acid residues are derived for
      the first time. The contribution constants are extended to 59 unmodified regular
      peptides with the inclusion of the pka values of both N-terminal and C-terminal
      amino acids. The models thus obtained have been validated with additional 27
      peptides (both N-acetyl-peptide-amides and unmodified). CONCLUSIONS: The Log P of
      oligopeptides is very well correlated with the de novo hydrophobic contribution
      constants of amino acids. The models we have derived are reasonably accurate in
      predicting the hydrophobicities of new oligopeptides (< or = tetrapeptides) at a
      fixed pH (e.g., 7).

PMID- 8570522
TI  - Precipitation of insulinotropin in the presence of protamine: effect of phenol
      and zinc on the isophane ratio and the insulinotropin concentration in the
      supernatant.
AB  - PURPOSE: The purpose of this study is to determine the minimum quantity of
      protamine required for the completion of insulinotropin precipitation under
      different precipitation conditions. METHODS: The experiments involved combining
      insulinotropin with varying concentrations of protamine in pH 7.2 phosphate
      buffered saline and analyzing the concentrations of both proteins in the
      supernatant. Isophane ratio (the protamine/insulinotropin molar ratio that
      results in a minimum total protein concentration in the supernatant) was
      determined for different precipitation conditions. RESULTS: When neutral
      solutions of insulinotropin (pI 5.3) and protamine (pI 13.8) were combined,
      precipitation did not occur. However, in the presence of phenol and/or zinc,
      insulinotropin co-precipitated with protamine. In the presence of phenol, the
      isophane ratio and the insulinotropin concentration in the supernatant were
      determined to be 0.08 and 0.18 mg/ml, respectively. In the presence of zinc, the
      isophane ratio increased with zinc concentration, apparently from the
      precipitation of protamine in the presence of zinc. The isophane ratio and the
      insulinotropin concentration in the supernatant were 0.13 and 0.13 mg/ml,
      respectively, when the zinc/insulinotropin molar ratio was one. In the presence
      of phenol and zinc with the zinc/insulinotropin molar ratio of 1.0, the isophane
      ratio and the insulinotropin concentration in the supernatant were 0.11 and 1
      microgram/ml, respectively. CONCLUSIONS: A method to determine the isophane ratio
      of protamine/insulinotropin precipitation was developed to determine the minimum
      quantity of protamine required for the completion of insulinotropin precipitation
      under different precipitation conditions. A synergistic effect between phenol and
      zinc on the precipitation of insulinotropin in the presence of protamine was
      found.

PMID- 8570523
TI  - Cholate-induced disruption of calcitonin-loaded liposomes: formation of trypsin
      resistant lipid-calcitonin-cholate complexes.
AB  - PURPOSE: The work was performed to obtain a better understanding why the oral
      administration of calcitonin (CT)-loaded liposomes to rats results in a
      hypocalcemia, while liposomes are normally disrupted in the gastro-intestinal
      tract and cannot protect the hormone from enzymatic digestion. METHODS: In vitro
      comparisons between the stability of calcein and CT-loaded liposomes in the
      presence of cholate solutions led to an interpretation of the results observed.
      By means of gel filtration, turbidimetry, and fluorescence measurements, the
      interactions between CT and lipids were studied after sonicated liposomes had
      been broken down by cholate. RESULTS: Experiments showed that CT in the external
      medium of a liposome suspension had no effect on the vesicles. Gel filtration of
      cholate-treated liposomes loaded with calcein and CT resulted in a total
      separation of calcein from the lipid fraction for detergent concentrations higher
      than 4 mM. However, 50% of the CT was reencapsulated even when the cholate-to
      phospholipid molar ratio was increased up to 100. Incubation of cholate
      solubilized liposomes with 1% trypsin resulted in a partial CT-breakdown.
      CONCLUSIONS: These results strongly suggest that during membrane solubilization
      by cholate, lipid-CT complexes are formed which retain most of the CT initially
      embedded in the liposomal membrane, and which offer some protection to CT under
      the action of trypsin. The existence of these complexes could be one of the
      reasons for the reported hypocalcemia in rats after oral administration of CT
      loaded liposomes.

PMID- 8570524
TI  - Mucoadhesive polymers in peroral peptide drug delivery. II. Carbomer and
      polycarbophil are potent inhibitors of the intestinal proteolytic enzyme trypsin.
AB  - PURPOSE: The evaluation of the inhibitory action of two mucoadhesive
      poly(acrylates), polycarbophil and carbomer, registered by the Food and Drug
      Administration (FDA), on the intestinal proteolytic enzyme trypsin. METHODS: The
      effect of the polymers on trypsin activity by measuring the degradation of a
      trypsin specific substrate. Binding of Ca2+ ions and proteins (125I-BSA) to the
      poly(acrylates). The influence of the polymers on the secondary trypsin structure
      by circular dichroism. RESULTS: Trypsin inhibition was found to be time-dependent
      upon addition of Ca2+ in the degradation experiment. Only when Ca2+ was added
      within 10 min after trypsin incubation, recovery of the enzyme could be observed.
      Both polymers showed a strong Ca2+ binding ability. Carbomer, which had a higher
      inhibitory effect on trypsin activity, also revealed a higher Ca2+ binding
      affinity than polycarbophil. The amount of Ca2+ depleted out of the trypsin
      structure and the reduction of enzyme activity were comparable. Immobilization of
      trypsin by binding to the polymers could not be observed at pH 6.7. Circular
      dichroism studies suggested that, under depletion of Ca2+ from trypsin, the
      secondary structure changed its conformation, followed by an increased
      autodegradation of the enzyme. CONCLUSIONS: The poly(acrylates) investigated may
      have potential to protect peptides from tryptic degradation and may be used to
      master the peroral delivery of peptide drugs.

PMID- 8570525
TI  - The intestinal transport mechanism of fluoroquinolones: inhibitory effect of
      ciprofloxacin, an enoxacin derivative, on the membrane potential-dependent uptake
      of enoxacin.
AB  - PURPOSE: To clarify the absorption-structure relationship for the
      fluoroquinolones from the point of view of inhibitory behavior. METHODS: The
      inhibitory effects of ciprofloxacin on the transport process of enoxacin across
      the rat intestinal brush-border membrane was examined. RESULTS: Ciprofloxacin,
      which has a similar structure to enoxacin, exhibited a pH-dependent interference
      with enoxacin absorption from rat jejunal loops. The uptake experiments using BBM
      vesicles showed that ciprofloxacin significantly reduced not only the initial
      binding of enoxacin to the membrane surface, but also the K(+)- or H(+)-diffusion
      potential-dependent transport across the membrane. Furthermore, an H(+)-diffusion
      potential (interior negative) also exhibited a stimulative uptake of
      ciprofloxacin. CONCLUSIONS: These results suggest that the inhibition behavior of
      ciprofloxacin from the jejunal loop was closely related to the ionic diffusion
      potential-dependent uptake of enoxacin across the brush-border membrane.

PMID- 8570526
TI  - Possible involvement of multiple P-glycoprotein-mediated efflux systems in the
      transport of verapamil and other organic cations across rat intestine.
AB  - PURPOSE: We investigated the intestinal transport of verapamil, chlorpromazine,
      and propantheline, particularly their P-glycoprotein-mediated secretion. METHODS:
      Permeation of rat intestinal segments in vitro was determined using diffusion
      cells. RESULTS: Verapamil permeation in the serosal-to-mucosal direction was much
      greater than in the mucosal-to-serosal direction using duodenal, jejunal, and
      colonic membranes. The concentration dependence of jejunal permeation in the
      absorptive and secretory directions was consistent with saturability of a
      secretory transport system. Using a monoclonal antibody to inhibit P-glycoprotein
      mediated secretion caused a significant enhancement of verapamil absorption
      through the jejunum. In contrast, the rat ileum did not preferentially transport
      verapamil in the secretory direction, and the P-glycoprotein antibody had no
      effect on ileal absorption. Chlorpromazine and propantheline enhanced the mucosal
      to-serosal permeation of verapamil through the jejunum, most likely due to
      competitive inhibition of the P-glycoprotein-mediated secretory process.
      Vinblastine, tetraethylammonium, and guanidine did not affect verapamil
      permeation. Propantheline was also a substrate for P-glycoprotein-mediated
      secretory transport, but in contrast to verapamil, propantheline secretory
      transport was expressed in rat ileum. CONCLUSIONS: These results suggest that
      these cationic compounds are transported by plural P-glycoprotein-mediated efflux
      systems with different substrate specificities depending on the intestinal site.

PMID- 8570527
TI  - Regional gastrointestinal absorption of ranitidine in the rat.
AB  - PURPOSE: Ranitidine absorption from isolated segments of rat small intestine
      (duodenum, midgut, and terminal ileum) was investigated to examine the influence
      of pH and 50% bile, and to determine if ranitidine is absorbed preferentially
      from a specific region. METHODS: Ranitidine (50 mg/kg) was administered into each
      segment in pH 5 or pH 7 buffer, or in 50% bile. Venous blood was collected at
      various times for 40 min from the right jugular vein. RESULTS: When ranitidine
      was administered in pH 7 buffer or in 50% bile, Cmax and AUC0-40 were
      significantly greater after administration into the terminal ileum compared to
      the duodenum and midgut. AUC0-40 was significantly greater when ranitidine was
      administered in pH 5 buffer or in 50% bile into the duodenum compared to the
      midgut. Cmax was significantly different between administration into the duodenum
      and midgut only when ranitidine was administered in 50% bile. Ranitidine
      administration in pH 5 buffer significantly decreased AUC0-40 and Cmax after
      administration into the midgut, and AUC0-40 after administration into the
      terminal ileum compared to administration with pH 7 buffer or in 50% bile. Bile
      had no significant effect on AUC0-40 after ranitidine administration into the
      duodenum and midgut compared to administration in pH 7 buffer. However, bile
      significantly increased AUC0-40 and Cmax after ranitidine administration into the
      terminal ileum compared to administration with pH 7 and pH 5 buffer. CONCLUSIONS:
      Results suggest that ranitidine is absorbed from the entire small intestine.
      However, the terminal ileum is the optimal site of gastrointestinal absorption.
      Furthermore, bile enhances ranitidine absorption from the terminal ileum.

PMID- 8570528
TI  - Gastrointestinal transit and distribution of ranitidine in the rat.
AB  - PURPOSE: Ranitidine gastrointestinal distribution was examined in the rat small
      intestine after oral administration to determine whether intestinal transit or
      secretion (exsorption) may influence the appearance of secondary peaks in
      ranitidine serum concentration-time profiles. METHODS: Male Sprague-Dawley rats
      received ranitidine (50 mg/kg) by oral gavage, and the mass of ranitidine
      recovered in all small intestinal segments (approximately 12 cm each) was
      determined 30, 60, 90, or 120 min after administration. In a separate group of
      anesthetized rats, the small intestine was divided into two segments of equal
      length that were perfused with normal saline in a single-pass manner. Rats
      received an escalating, zero-order IV infusion of ranitidine for 30 min, and
      venous blood and intestinal effluent were collected over 90 min to quantitate
      ranitidine exsorption. RESULTS: Thirty min after oral administration, > 50% of
      the recovered ranitidine mass resided in the lower half of the small intestine in
      all rats. Ranitidine mass in 5 of 16 rats displayed a bimodal distribution with
      significant amounts of ranitidine recovered from the stomach 60 to 90 min after
      dosing. Ranitidine exsorption was more efficient from the lower jejunum and ileum
      than from the duodenum and upper jejunum. However, intestinal secretion of
      ranitidine was minor (5% of the IV dose). CONCLUSIONS: Ranitidine absorption from
      the lower ileum contributes significantly to systemic ranitidine concentrations
      before and during the time of the first concentration maximum. Separation of the
      drug mass into multiple boluses may contribute to secondary peaks in ranitidine
      concentration-time profiles. Exsorption did not contribute significantly to
      ranitidine distribution in the gastrointestinal tract.

PMID- 8570530
TI  - Drug delivery studies in Caco-2 monolayers. IV. Absorption enhancer effects of
      cyclodextrins.
AB  - PURPOSE: The purpose of the present study was to use the human colorectal
      carcinoma cell line. Caco-2, as a human intestinal epithelial model for studying
      the effects of cyclodextrins as absorption enhancers. METHODS: Cyclodextrins of
      varying sizes and physicochemical characters were investigated. The effects of
      the cyclodextrins were evaluated by means of staining of the cytoplasma and
      determination of the mitochondrial dehydrogenase activity as well as by transport
      enhancement of the macromolecular pore marker polyethylene glycol 4000 (PEG-4000)
      across the Caco-2 monolayers. RESULTS: The transport enhancing properties of the
      cyclodextrins were found to follow the lipophilicity of the core in their cyclic
      structure. Dimethyl-beta-cyclodextrin was the most powerful in all aspects and
      caused an increase in the permeability of the cytoplasma membrane in a
      concentration dependent manner. It was possible to increase the overall transport
      of PEG-4000 10-fold by the use of dimethyl-beta-cyclodextrin in low
      concentrations where the toxic effects on the monolayers were insignificant. It
      was further observed that the basolateral membrane was significantly more
      sensitive to cyclodextrins than the apical membrane. CONCLUSIONS: Since dimethyl
      beta-cyclodextrin was able to produce an absorption enhancing effect on PEG-4000
      in concentrations where the toxic effects on Caco-2 monolayers were low it is
      worth to pursue the compound as an absorption enhancer.

PMID- 8570529
TI  - First-pass accumulation of salicylic acid in gut tissue after absorption in
      anesthetized rat.
AB  - PURPOSE: The purpose of this paper is to report the study on the first-pass
      accumulation kinetics of salicylic acid (SA) in gut tissue after absorption by
      simultaneously analyzing drug contents in the lumen, gut tissue, and blood in
      anesthetized rats. METHODS: Sodium salicylate (5.4 mg as SA) in 0.4 ml normal
      saline was administered into a closed 10-cm jejunal loop. Drained mesenteric
      blood from the loop area was collected every minute, while lost blood was
      replaced through infusion of oxygenated blood from donor rats. At 3, 10, 20, 40,
      or 60 min after dosing, SA remaining in lumen, accumulating in gut tissue, and
      appearing in blood were analyzed by HPLC. All the data were fitted into a linear
      two-consecutive (lumen and gut tissue) first-order kinetic model. RESULTS: After
      absorption, significant amounts of SA accumulated in gut tissue before appearing
      in blood, e.g., at 3 or 20 min after dosing, 74.4 or 54.4% of absorbed SA
      accumulated in gut tissue, respectively. Practically all administered SA was
      recovered. The estimated mean absorption time from the lumen and mean transit
      time in gut tissue of SA were 20.4 and 18.5 min, respectively. CONCLUSIONS: The
      above results indicate that gut tissue may act as a reservoir for drug
      accumulation during the first pass after oral absorption. Thus, the rate of
      transport of drug into blood circulation after oral administration may
      significantly differ from the true rate of absorption through the gut membrane.
      The potential transport resistance from gut tissue to blood should probably be
      considered in the modeling of GI absorption.

PMID- 8570531
TI  - New evaluation method for in vitro/in vivo correlation of enteric-coated multiple
      unit dosage forms.
AB  - PURPOSE: To establish the evaluating method for drug dissolution profiles in the
      gastrointestinal (GI) tract based on in vitro data for the enteric-coated
      multiple unit. METHODS: Dissolution profile in the GI tract was calculated by the
      convolution procedure using an in vitro dissolution profile as a weighting
      function, and the gastric-emptying (GE) process as an input function (GE
      convolution method). A computer program, GECONV, was developed for numerical
      execution of the convolution integral. RESULTS: The in vivo dissolution profile
      of enteric-coated aspirin granules estimated by GE-convolution was in good
      agreement with the in vivo cumulative absorption profile calculated by the Wagner
      Nelson method using the plasma concentration data after oral administration to
      healthy subjects. The in vitro/in vivo correlation improved markedly by taking
      the GE process into consideration. CONCLUSIONS: These findings indicated that
      this convolution method is useful for estimating the in vivo dissolution profile
      of drugs, when they are administered in an enteric-coated multiple unit type
      dosage form, because the gastric emptying process is a determinant process for
      the in vivo drug dissolution.

PMID- 8570532
TI  - Development and in vitro-in vivo evaluation of a multiparticulate sustained
      release formulation of diltiazem.
AB  - PURPOSE: To develop and evaluate the in vitro/in vivo performance of diltiazem
      sustained release pellets that were prepared by the Wurster column process.
      METHODS: Pellets containing diltiazem were prepared by spraying a slurry of
      micronized diltiazem hydrochloride, pharmaceutical glaze and alcohol onto an
      appropriate mesh fraction of nonpareil seeds using the Wurster column. A two-step
      drug layering process was used to increase drug loading from 60% to 75%. The oven
      dried diltiazem basic pellets were coated with ethylcellulose/dibutyl sebacate
      coating solution to yield diltiazem sustained release pellets. An open,
      randomized Latin square, three-way crossover clinical study was used to evaluate
      the in vivo performance of the coated product. RESULTS: Altering the mesh
      fraction of the starting nonpareil seeds for this layering process was found to
      affect the release characteristics of drug from the pellets. An oven-drying step
      was required to stabilize the diltiazem basic pellets. The thicker the drug
      loading layer the longer the oven drying is needed to stabilize the pellets. The
      diltiazem sustained release pellets produced by these methods displayed sustained
      release dissolution profiles both in vitro and in vivo. Diltiazem basic pellets
      coated with a 0.6% ethylcellulose/dibutyl sebacate coating showed a different
      rate of absorption (lower Cmax and higher Tmax) and the same extent of absorption
      as compared to Cardizem tablets. CONCLUSIONS: Clinical data confirmed that this
      formulation approach is an effective means to produce a diltiazem sustained
      release product.

PMID- 8570533
TI  - The pulmonary absorption of aerosolized and intratracheally instilled rhG-CSF and
      monoPEGylated rhG-CSF.
AB  - PURPOSE: The objective of this study was to highlight differences in the
      pulmonary absorption of a monoPEGylated rhG-CSF and rhG-CSF after intratracheal
      instillation and aerosol delivery. METHODS: Male Sprague Dawley rats (250 g) were
      anesthetized and intratracheally instilled (IT) with protein solution or were
      endotracheally intubated and administered aerosol for 20 min via a Harvard small
      animal ventilator. A DeVilbiss "Aerosonic" nebulizer containing 5 ml of protein
      solution at approximately 3 mg/ml was used to generate aerosol. The volume of
      protein solution deposited in the lung lobes was estimated to be approximately 13
      microliters after delivery of Tc-99m HSA solutions. The PEGylated proteins
      consisted of a 6 kDa (P6) or 12 kDa PEG (P12) linked to the N-terminus of rhG
      CSF. rhG-CSF also was administered IT in buffers at pH 4 and pH 7 and in dosing
      volumes ranging from 100 to 400 microliters. Blood samples were removed at
      intervals after dosing and the total white blood cell counts (WBC) were
      determined. Plasma was assayed for proteins by an enzyme immuno assay. RESULTS:
      The plasma protein concentration v. time profiles were strikingly different for
      aerosol v. IT delivery. The Cmax values for rhG-CSF and P12 after aerosol
      delivery were greater than found after IT (Aerosol: 598 +/- 135 (ng/ml) rhG-CSF;
      182 +/- 14 P12 v. IT: 105 +/- 12 rhG-CSF; 65.9 +/- 5 P12). Similarly, Tmax was
      reached much earlier after aerosol administration (Aerosol: 21.7 +/- 4.8 (min)
      rhG-CSF; 168 +/- 31 P12 v. IT: 100 +/- 17 rhG-CSF; 310 +/- 121 P12). Estimated
      bioavailabilities (F(lung)%) were significantly greater via aerosol delivery than
      those obtained after IT (Aerosol: 66 +/- 14 rhG-CSF; 12.3 +/- 1.9 P12 v. IT: 11.9
      +/- 1.5 rhG-CSF; 1.6 +/- 0.1 P12). An increase in circulating WBC counts was
      induced by all proteins delivered to the lungs. The rate and extent of absorption
      of rhG-CSF was not influenced by the pH employed nor the instilled volume.
      CONCLUSIONS: Estimates of bioavailability are dependent upon the technique
      employed to administer drug to the lungs. Aerosol administration provides a
      better estimate of the systemic absorption of macromolecules.

PMID- 8570534
TI  - Pharmacokinetics of 1-(2-deoxy-2-fluoro-beta-L-arabinofuranosyl)-5-methyluracil
      (L-FMAU) in rats.
AB  - PURPOSE: The objective of this study was to characterize the pharmacokinetics of
      1-(2-deoxy-2-fluoro-beta-L-arabinofuranosyl)-5-methyluracil (L-FMAU), a
      nucleoside analogue with potent activity against the hepatitis B virus and the
      Epstein-Barr virus, in rats. METHODS: Three doses of L-FMAU were administered
      intravenously (10, 25, and 50 mg/kg) to rats, and L-FMAU concentrations in plasma
      and urine were measured by HPLC. Pharmacokinetic parameters were generated by
      using area-moment analysis. RESULTS: There were no significant differences in the
      pharmacokinetic parameters between the three doses (alpha < 0.05). Thus, the
      disposition of L-FMAU was linear over the dosage of 10 to 50 mg/kg. Plasma
      concentrations of L-FMAU declined rapidly with a terminal phase half-life of 1.33
      +/- 0.45 h (mean +/- SD). Total clearance of L-FMAU was moderate, averaging 1.15
      +/- 0.28 L/h/kg. The fraction of compound excreted unchanged in urine was 0.59 +/
      0.13. No glucuronide metabolite was found in the urine. The steady-state volume
      of distribution was 1.12 +/- 0.26 L/kg indicating intracellular distribution of
      the compound. The fraction of L-FMAU bound to plasma proteins was approximately
      15% and was independent of nucleoside concentration. CONCLUSIONS: The
      pharmacokinetics of L-FMAU in rats were independent of dose over the dosage range
      of 10 to 50 mg/kg.

PMID- 8570535
TI  - Absorption of sunscreens and other compounds through human skin in vivo:
      derivation of a method to predict maximum fluxes.
AB  - PURPOSE: The goal of this study was to quantify the transdermally absorbed
      amounts of the sunscreens octyl dimethyl p-aminobenzoic acid, oxybenzone, 4
      isopropyl-dibenzoylmethane, 3-(4-methylbenzylidene)-camphor, isoamyl-4
      methoxycinnamate, the repellent and plasticizer dibutyl phthalate, the
      antioxidant 3.5-di-t-butyl-4-hydroxyanisol, and the antimicrobial compounds butyl
      4-hydroxybenzoate, biphenyl-2-ol, and 2,4,4'-tri-chlor-2'-hydroxydiphenylether
      (triclosane). Permeabilities PB and maximum fluxes Jmax should be correlated with
      relevant physicochemical properties. METHODS: Saturated solutions of the above
      mentioned compounds in a propylene glycol/water mixture were applied to the skin
      using glass chambers which were fixed to the upper arms of volunteers. Maximum
      fluxes were calculated from concentration decreases in the vehicle. RESULTS: A
      linear relationship between the logarithms of permeabilities PB of the penetrants
      (0.02-0.28 cm h-1) and the corresponding octanol/vehicle partition coefficients
      PCOct/V (166-186,208) was found. Consequently, the influence of aqueous boundary
      layers could be neglected. However, the slope of the resulting straight line of
      0.38 is considerably smaller than unity indicating that PCOct/V does not
      represent the lipophilicity of the stratum corneum adequately. Maximum fluxes
      range from 0.5 to 130 micrograms cm-2 h-1. A general equation for the calculation
      of Jmax was derived based on experimental data taking into account the PCOct/V
      and the solubilities CsV of the respective penetrants in the vehicle.

PMID- 8570536
TI  - Hydrolysis of the prodrug, 2',3',5'-triacetyl-6-azauridine.
AB  - PURPOSE: The purposes were to study the kinetics of hydrolysis of 2',3',5'
      triacetyl-6-azauridine (1) in aqueous solution (mu = 0.5) and to identify the
      main intermediates and products of the reaction. METHODS: A stability indicating
      isocratic LC assay was used to study the rate of degradation of 1. A gradient LC
      assay was used to study the time courses of the degradants. The products of
      hydrolysis were isolated by preparative liquid chromatography and identified by
      1H-NMR and CI-MS. The pKa value was obtained by potentiometric titration.
      RESULTS: At 36.8 degrees C, the pH-rate profile of 1 in water was adequately
      described by a four-term rate equation. The intermediates were identified as the
      primary and secondary di-acetates, and the primary and secondary mono-acetates.
      The final product was 6-azauridine. CONCLUSIONS: A simplified kinetic scheme
      could be used to describe the concentration-time profiles of 1, the intermediates
      and the final product.

PMID- 8570538
TI  - Measurement of the diffusion of 2,2,2-trifluoroacetamide within thermoresponsive
      hydrogels using NMR imaging.

PMID- 8570537
TI  - Hydroxypropyl-beta-cyclodextrin increases the aqueous solubility and stability of
      pilocarpine prodrugs.
AB  - PURPOSE: The effects of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the
      aqueous solubility and stability of two lipophilic bispilocarpine prodrugs were
      investigated at pH 7.4. METHODS: The solubility of prodrugs was studied by phase
      solubility method (0-72.5 mM HP-beta-CD). The stability of one of the prodrugs
      was investigated as a function of temperature (40 degrees C-70 degrees C) and HP
      beta-CD concentration (0-72.5 mM). The apparent rate constants (k1, k2) for
      degradation of prodrug in 1:1 and 1:2 inclusion complexes and apparent stability
      constants (K1:1, K1:2) were calculated by the curve-fitting method. RESULTS: The
      phase-solubility diagrams were classified as Ap-type and the apparent stability
      constants (K1:1, K1:2) for 1:1- and 1:2-inclusion complexes were calculated to be
      143-815 M-1 and 29-825 M-1, respectively. The stability of prodrug increased as a
      function of HP-beta-CD concentration over the studied temperature range. The
      shelf-life (t90%, calculated by the Arrhenius equation) of the prodrug in 72.5 mM
      HP-beta-CD solution increased 5.1-fold and 6.1-fold at 25 degrees C and 4 degrees
      C, respectively. CONCLUSIONS: The solubility of the prodrugs was shown to
      increase markedly in phase-solubility studies. The degradation rate of prodrug in
      stability studies was shown to be slower in the 1:2-complex than in the 1:1
      complex and the relative amounts of complex species were found to be dependent on
      CD concentration.

PMID- 8570539
TI  - Particle size distribution of single and multiple sprays of salbutamol metered
      dose inhalers (MDIs).

PMID- 8570540
TI  - Influence of surface properties on the inflammatory response to polymeric
      nanoparticles.

PMID- 8570541
TI  - Evidence for the lack of a human metabolic isotope effect of a deuterium analog
      of fluphenazine.

PMID- 8570555
TI  - [Gerhard Domagk, 100th birthday of the pathologist and Nobel Prize winner].

PMID- 8570556
TI  - [Thrombosis and phlebitis of superficial veins. Differential histopathologic
      diagnosis].
AB  - Primary thrombosis and phlebitis with secondary thrombosis of superficial veins
      are frequent. A biopsy may be performed if the clinician suspects an underlying
      systemic disease. The pathologist must be aware of the different types and their
      etiology because the further diagnostic and therapeutic procedures depend on his
      evaluation. The different types of primary thrombotic and primary phlebitic
      disorders are described and their possible etiology is discussed.

PMID- 8570557
TI  - [Standardized documentation of patho-anatomic findings using ADT (Association of
      German Tumor Centers) tumor forms for malignancies of the mouth, jaw and face
      (version III)].
AB  - The documentation form for pathohistologic findings (version III) for tumors of
      the maxillofacial region is presented. It is part of the site-specific
      documentation of the German Association of Tumor Centers (ADT). Its handling is
      explained by instructions which are based on the ICD-O classification and the TNM
      system. The prognostic relevance of the standardized documentation has already
      been proven by various histomorphologic investigations concerning oral and
      oropharyngeal cancer. By means of a multicentric observational study the German
      Austrian Swiss co-operative group DOSAK will develop a new prognostic model for
      oral and oropharyngeal cancer.

PMID- 8570558
TI  - [Prognostic value of immunohistochemical determination of urokinase plasminogen
      activator in primary breast cancers].
AB  - There is ample evidence that the protease urokinase plasminogen activator (uPA)
      plays a role in invasion and spread of tumours. Several publications suggest its
      biochemical measurement in tumour cytosols to be of prognostic significance in
      breast carcinomas. Our study set out to determine whether the immunohistochemical
      detection of uPA in formalin-fixed, paraffin-embedded primary breast cancer
      tissues is of prognostic relevance. We tested 269 surgical specimens of primary
      ductal infiltrating carcinoma immunohistochemically using a modified avidin
      biotin method. Some 57% of carcinoma specimens yielded specific positive staining
      in tumour cells. Detection of uPA correlated to tumour grade (P = 0.04), and to
      the detected level of the proliferation marker PCNA (P = 0.002), but not to
      patients' age or menopausal status, tumour size, nodal or steroid receptor status
      (P > 0.05). At median 68 months' follow-up, 34% of patients had experienced
      tumour relapse and 28% had died from cancer. Clinical course was correlated
      significantly to tumour size, tumour grade, nodal and steroid hormone receptor
      status (P < 0.05). Immunohistochemical detection of uPA, however, could not be
      demonstrated to be of any prognostic significance with regard to relapse-free or
      overall survival (P > 0.05) in the total study group or in the N0 (n = 120) and N
      + (n = 144) subgroups, regardless of whether univariate or multivariate analysis
      was applied.

PMID- 8570559
TI  - [Nerve-neuroendocrine complexes in stomach mucosa in Zollinger-Ellison syndrome].
AB  - Nerve fibre-neuroendocrine cell complexes (NF-NEC-C's) are neuroendocrine cells
      located in the lamina propria of the gastro-intestinal tract directly connected
      with nerve fibres of Meissner's plexus. We report on a patient with sporadic
      Zollinger-Ellison syndrome (ZES) with electron microscopically demonstrated
      multiple NF-NEC-C's in non-antral gastric mucosa. It is suspected that in ZES the
      hypergastrinaemia may represent a trophic stimulus for the proliferation of NF
      NEC-C's in the gastric mucosa.

PMID- 8570560
TI  - [Colon carcinoma simulating retroperitoneal inflammatory pseudotumor. Case report
      of so-called abdominal inflammatory fibrosarcoma].
AB  - Resection of a stenosing colon tumor in an 89-year-old male patient led to the
      diagnosis, unusual at this age, of an inflammatory pseudotumor (synonym: plasma
      cell granuloma) of the retroperitoneum and mesentery, which invaded the large
      bowel and showed infiltration of one regional lymph node. Histology and
      immunohistochemistry (demonstrating a myofibroblastic phenotype of the
      proliferating spindle cells and polyclonality of abundantly present plasma cells)
      of the specimen resembled previously reported lesions in various locations. The
      etiology and exact nosological classification of inflammatory pseudotumors are
      not yet unequivocally settled. The recently published conjecture that such
      lesions of the retroperitoneum represent a separate entity with features of a
      malignant neoplasm is discussed.

PMID- 8570561
TI  - [Inflammatory pseudotumor of the liver. Morphologic and cytophotometry studies
      and differential diagnosis].
AB  - Inflammatory pseudotumors of the liver are extremely rare. Worldwide only 50
      cases have been described so far. In lung tissue, their incidence is higher, with
      119 cases being published. Etiological factors are still a matter of debate;
      reactive inflammatory processes have recently been proved by immunohistological
      and cytophotometric studies. This seems to be true for both liver and lung
      locations of inflammatory pseudotumors. Considerable morphological
      heterogeneities, conspicuously varying from one case to another, reflect the
      numerous synonyms that have been created for this condition, i.e., plasma cell
      granuloma, xanthoma, fibroxanthoma, histiocytoma, plasmacytoma, solitary "mast
      cell tumor" and pseudoneoplastic pneumonia, just to number a few of them. This
      multicolored morphology explains the difficulties in histologic diagnosis,
      especially if needle biopsies or frozen sections are submitted to pathology.
      Differential diagnosis of an inflammatory pseudotumor of the liver needs to
      include fibrohistiocytic neoplasia if spindle-cell-shaped areas are included or,
      on the other hand, parenchymal infiltrates of the nodular sclerosing type of
      Hodgkin's granuloma. Immunohistological investigations do not allow final
      decisions since spindle-shaped cells within pseudotumours can express vimentin
      and/or desmin as well. Such histological cases should always include the excision
      of a piece of liver tissue of sufficient size to comfortably allow for the
      recognition of the multicellular composition and morphological heterogeneity of
      this process.

PMID- 8570562
TI  - [Uterine stromal tumor with ovarian sex cord differentiation].
AB  - Uterine tumors resembling sex-cord ovarian structures are exceptionally rare.
      Clement and Scully divided them into two groups. The first group includes cases
      with less than 50% and the second with more than 50% sex-cord elements. Group one
      tumors show a higher incidence of recurrences. We report a case of a 54-year-old
      women with a partly retroperitoneal, cystic tumor 7.6.6 cm. Histologically, sex
      cord differentiation of more than 50% was seen with positive immunostaining
      against vimentin, desmin and focally against myoglobin and cytokeratines. The
      reaction against EMA, CEA and S 100 was negative. The patient was treated by
      abdominal hysterectomy with bilateral salpingo-oovorectomy. She shows no evidence
      of disease 2.3 years after the initial surgery. Based on the light microscopic
      features and immunohistochemical pattern, the tumor was interpreted as arising
      from the endometrial stromal cells or multipotential uterine mesenchyme that
      showed diverse differentiation toward ovarian sex-cord stroma and uterine smooth
      muscle with interspersed stromal cell clusters.

PMID- 8570563
TI  - [Sarcomatoid carcinoma of the bladder in a 25-year-old man].
AB  - A 25-year-old patient with a rapidly growing sarcomatoid carcinoma of the urinary
      bladder is reported. The diagnosis was made on the basis of extended atypical
      proliferations of spindle or pleomorphic cells in the area of pelvic floor and
      the radix of the penis. The tumor showed invasion of the blood and a high Ki-67
      growth fraction up to 40%. Immunohistochemically, the reactions with antibodies
      against cytokeratin, EMA, and vimentin were positive, while negative results were
      obtained in reactions with antibodies against desmin, actin, PSA, S 100, human
      epithelial antigen (Ber-EP4), and cytokeratin 13. The differential diagnosis
      against myosarcomas, pseudosarcomatous lesions, and inflammatory pseudotumours is
      discussed. After radical surgery a pelvic recurrence and pulmonary metastases
      developed, which led to the patient's death 3 months later. This case shows that
      sarcomatoid carcinomas of the urinary bladder can be found even in young people.

PMID- 8570564
TI  - [Oncocytoma of the nose. A case report and review of the literature].
AB  - Oncocytomas are rare epithelial tumors of the major and minor salivary glands.
      Reported is an oncocytoma of the lateral wall of the left nasal cavity in a 60
      year-old man. Because of its locally invasive character, with rupture into the
      left nasal cavity and partial dedifferentiation with loss of typically oncocytic
      features, we classified the tumor as oncocytoma of low malignant potential.

PMID- 8570565
TI  - [Interstitial nephritis with acute renal failure in Ascaris lumbricoides
      infection].
AB  - A girl aged 14 years, 8 months presented with painful swelling of cervical lymph
      nodes. On frozen section malignancy could be ruled out. There were nonspecific
      inflammatory changes. In the presence of a prominent eosinophilic reaction the
      possibility of a drug reaction had been suggested. Because of decreasing renal
      function, dialysis was started 1 day after lymph node extirpation. A renal biopsy
      revealed acute interstitial nephritis-again with eosinophils. At this point
      parasitosis was discussed. There was a slightly elevated titer for filariasis.
      Shortly thereafter, also eggs of Ascaris lumbricoides were found in the feces. A
      pulmonary infiltrate made its appearance, with eosinophils in the pleural fluid.
      About 20 days later, after dialysis and anti-Ascaris therapy, the patient was
      discharged with no further complaints. Repeated controls revealed no further
      complaints, especially no more Ascaris lumbricoides. This case had two special
      aspects: (1) initial presentation with painful cervical lymph node swelling, and
      (2) subsequent acute renal failure. The literature revealed only four patients
      with Ascaris lumbricoides infection and acute interstitial nephritis, all
      described by one author (Zollinger). Perhaps a special hyperergic situation in
      this patient was responsible for the renal involvement; however, this
      complication should be watched for in all cases Ascaris lumbricoides infections.

PMID- 8570566
TI  - [Computer-assisted speech recognition in diagnostic pathology. Development of the
      DragonDictate-30 K system for documentation].
AB  - The speech recognition system DragonDictate-30 K is the first commercially
      available product for personal computers (PC) that includes a thesaurus of 30,000
      words which can replace the computer keyboard completely for report writing. The
      system is speaker-adaptative, i.e., it can learn the phonetic pattern of the
      pathologist's voice. We have developed a thesaurus with special terms from the
      field of diagnostic pathology to shorten the time-consuming training phase.
      DragonDictate is compatible with all text-oriented DOS computer software tools.
      The recommended minimal hardware configuration is a personal computer with a
      80,486 processor with 16 MB on board and a 200 MB hard disk.

PMID- 8570567
TI  - A rapid method for the isolation of genomic DNA from Aspergillus fumigatus.
AB  - A majority of Aspergillus induced diseases are reported to be caused by
      Aspergillus fumigatus. In immunocompromized and post transplant cases it can lead
      to invasive aspergillosis. Due to this the molecular fingerprinting of
      aspergillus isolates by RFLP analysis and development of DNA diagnostic probes
      are gaining importance. Different methodologies are being adopted for extraction
      of the genomic DNA from fungus. The existing procedures for isolation of DNA are
      time consuming and range from several hours to few days. The most difficult step
      in the isolation of DNA from aspergillus species is to disrupt the tough chitin
      rich cell wall without causing damage to genomic DNA. We report here a rapid
      method for extraction of genomic DNA based on the cleavage of chitin with
      chitinase. The subsequent modification steps included are lysis and microwave
      treatment. The chromosomal DNA obtained by this procedure is 1.5-2.0 micrograms
      per mg of wet weight of mycelia and is observed to be minimally sheared. It is
      pure enough for restriction analysis and for use in the PCR to detect the gene
      coding for 18 kDa allergen which has been identified in our laboratory using
      western blot analysis with human patient sera.

PMID- 8570568
TI  - Purification of chlorpromazine-sensitive GTPase from rat cerebral cortex.
AB  - The chlorpromazine-sensitive GTPase from the cell membrane of rat cerebral cortex
      was purified to homogenity by using DEAE Bio-Gel A agarose, hydroxyapatite and
      heparin agarose chromatography. The purified chlorpromazine-sensitive GTPase was
      purified 370-fold to obtain a final specific activity of 40 mumol GTP
      hydrolyzed2min/mg protein. The purified enzyme was inhibited by chlorpromazine
      but not by compound 48/80. Magnesium was required for its activity instead of
      calcium. The purified enzyme had an apparent pH optimum of 8.0, and molecular
      weight was estimated to be 58,000.

PMID- 8570569
TI  - Evaluation of a purification procedure for the muscarinic receptor for the
      purpose of quantitative receptor assays of anticholinergics. Part A: The membrane
      bound receptor.
AB  - The presented purification procedure for the muscarinic receptor from calf
      striatum includes the extraction of lipids with hexane in the first step and the
      removal of 39% of non-receptor proteins with 2 M NaCl in the second step. The
      simplicity of such an approach to the purification of the receptor warrants its
      use in the routine practice for quantitative purposes. The high affinity binding
      of tertiary 3H-dexetimide (3H-DEX) and quaternary 3H-N-methylscopolamine (3H-NMS)
      is preserved after the removal of irrelevant lipids and proteins from the P2
      pellet. The overall yield of receptors--80%, when labelled with 3H-NMS, was
      satisfactory. Moreover, the final product, the NaCl-pellet, exerts a higher
      density of 3H-NMS binding sites per mg proteins by a factor of about 1.7. The
      overall yield of receptors and purification factor were lower, when measured with
      3H-DEX. The total yield of 3H-DEX binding sites amounted to about 40% and the
      receptor density per mg protein decreased by a factor of 0.85. We did not succeed
      in the improvement of the ratio specific/non-specific binding, neither for 3H-DEX
      nor for 3H-NMS for the purified receptor preparations. The use of 3H-NMS is
      preferable to 3H-DEX in plasma sample assays because of a negligible effect of
      plasma on ligand binding when compared with 3H-DEX.

PMID- 8570570
TI  - Evaluation of a purification procedure for the muscarinic receptor for the
      purpose of quantitative receptor assays of anticholinergics. Part B: The
      solubilized receptor.
AB  - For the purpose of quantitative receptor assays, a three-step solubilization
      procedure including three optimization sets for muscarinic receptor from calf
      striatum was developed. The first step includes the extraction of the P2-pellet
      with n-hexane and consequently with 2 M NaCl. By the latter, 39% of non-receptor
      proteins was extracted. The resulting pellet (NaCl-pellet), enriched in
      muscarinic receptors by a factor of 1.5-1.7, was solubilized with 1% digitonin.
      The binding parameters of the solubilized receptor were determined for the
      tertiary 3H-dexetimide (3H-DEX) and the quaternary 3H-N-methylscopolamine (3H
      NMS). The resulting receptor density measured with 3H-dexetimide was lower (43.3%
      of that for the NaCl-pellet) than that for 3H-N-methyl-scopolamine (56.7%). The
      treatment with digitonin preserved the high affinity for 3H-N-methylscopolamine
      (Kd = 0.645 nM), however the affinity of 3H-dexetimide decreased after
      solubilization (Kd = 8.526 nM). The use of solubilized receptors in combination
      with hydrophilic 3H-NMS allows to increase the ratio specific/non-specific
      binding, since the non-specific binding for this ligand to the solubilized
      preparation is lower when compared with membrane-bound receptors. The above
      solubilization procedure was found preferable over directly solubilizing the P2
      pellet since (a) the receptor density for 3H-NMS was higher for the solubilized
      NaCl-pellet by a factor of about 1.7, and (b) the treatment of the P2-pellet with
      digitonin resulted in a lowering of the Kd to 2.422 nM. However, with respect to
      the plasma effect on the ligand binding, both solubilized preparations give
      similar results. The use of the solubilized NaCl-pellet or the P2-pellet can
      considerably improve the quantitative receptor assays of plasma samples. Unlike
      the membrane-bound receptor, a high volume of plasma, such as 400 microliters,
      can be added to the assay without any influence on the 3H-DEX binding when
      solubilized preparation is used.

PMID- 8570571
TI  - Current topic: the placental corticotrophin-releasing hormone
      adrenocorticotrophin axis.
AB  - In this review the factors regulating production of corticotrophin-releasing
      hormone (CRH) in intrauterine tissues are discussed and interactions of placental
      CRH with placental pro-opiomelanocortin (POMC)/adrenocorticotrophin (ACTH) and
      prostaglandins (PG) are examined. Discrepant results concerning localization of
      immunoreactive (IR-) CRH and its binding protein (CRH-BP) and their mRNAs in
      intrauterine tissues are described, and these issues require further resolution.
      It is suggested that the CRH-ACTH-PG axis in the placenta and choriodecidua may
      be important in relation to paracrine/autocrine regulation of uteroplacental
      blood flow, and in term and preterm labour. During the initial stages of preterm
      labour in the setting of infection, intrauterine cytokines and other factors may
      stimulate CRH output, implying a role for the immune-neuroendocrine axes in this
      process. With loss of chronic trophoblasts in advanced infection leading to
      preterm labour, a major intrauterine site of CRH production may be lost and the
      influence of this pathway becomes minimal. At this time increased intrauterine
      prostaglandin synthesis, together with loss of prostaglandin dehydrogenase
      activity in the fetal membranes, may become the primary route leading to
      myometrial activity and delivery.

PMID- 8570572
TI  - Placental prostanoid release in severe intrauterine growth retardation.
AB  - Our objective was to evaluate prostanoid release from the placentae of
      pregnancies complicated by severe intrauterine growth retardation (IUGR) and
      without hypertension, compared with placentae from normal, uncomplicated term
      pregnancies. A perifusion system was utilized to study the release of prostanoids
      6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2(TxB2),
      prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) from human
      placentae from pregnancies complicated by normotensive severe IUGR (n = 9, five
      at term and four preterm) and normal control pregnancies (n = 6). For each
      placenta, triplicate chambers of tissue were perifused at a rate of 6 ml/h, and
      samples were collected from hours 5-10. Prostanoids were measured using specific
      and sensitive radioimmunoassays. In the IUGR group, the basal placental
      production of the vasoconstrictor thromboxane was not increased, nor was the
      ratio of cumulative TxB2 to 6-keto-PGF1 alpha elevated compared with normal term
      controls. In three term IUGR placentae, the ratio was significantly decreased
      compared with controls. The basal placental production of the vasoconstrictor
      PGF2 alpha was likewise not increased compared with controls, nor was the ratio
      of PGF2 alpha to PGE2 elevated. Two of the placentae in the term IUGR group
      demonstrated significant elevations of PGE2 and 6-keto-PGF1 alpha. Overall, the
      IUGR placentae released normal or low normal levels of the prostanoids studied.
      The pattern of placental prostanoid release over time was similar to that of the
      normal term placentae. The term and preterm placentae of pregnancies complicated
      by severe IUGR did not exhibit an excess production of vasoconstrictor
      prostanoids. Therefore, strategies designed to reduce thromboxane production in
      severe IUGR without hypertension may be unjustified.

PMID- 8570573
TI  - Identification of 'renin'-containing cells in the choriodecidua.
AB  - Chorionic trophoblast, decidual cells, and macrophages have all been named as the
      site of renin in the placental membranes. To establish more clearly the nature of
      the renin-containing cells in the placental membranes, double immunostaining
      techniques were used to stain renin and specific cell markers in the same tissue
      sections. Cytokeratin was selected as an ectodermal cell marker and CD68 as a
      cytoplasmic macrophage marker. Cross-binding between antibodies was prevented by
      blocking species-related binding sites between the first and second sequence of
      the double-immunostaining procedures and by using highly selective immunostaining
      techniques in the second sequence. The results clearly show renin immunostaining
      in CD68-positive macrophages and not in cytokeratin-positive trophoblast. The
      anti-renal renin monoclonal antibody showed high affinity cross-reactivity with
      cathepsin D, another aspartic proteinase that can release angiotensin I from
      angiotensinogen. This should be seen in the context of earlier findings that only
      two of four anti-renal renin monoclonal antibodies showed staining in uterine and
      placental tissues and both cross-reacted with cathepsin D. The results indicate
      that differentiation between renin and cathepsin D and, possibly, other
      substances with shared properties and epitope homology deserves more attention
      than it has received thus far.

PMID- 8570574
TI  - Long-term effects of calcium availability on prolactin and protein synthesis in
      human decidual cells.
AB  - Ever since decidual cells were recognized as the source of decidual prolactin
      (dPRL), very few reports have dealt with the role of calcium (Ca2+) on dPRL
      synthesis and release. In a recent work, we described the presence of T-type Ca2+
      channels in these cells, giving Ca(2+)-dependent action potentials. However, we
      failed to demonstrate any action of decidual cell Ca2+ modulation on acute dPRL
      release, but observed only long-term effects. We have now investigated these
      effects on decidual protein and dPRL synthesis after 24 h treatments. When Ca2+
      channel blockers or EGTA (2 mM) were added to the culture medium, dPRL release
      and [3H] leucine incorporation into proteins decreased. Increasing external Ca2+
      up to 2 mM instead of 0.8 mM or changing the external K+ concentration (30 mM
      instead of 5.6) had no consequence on dPRL release, whereas 2 mM of Ca2+ enhanced
      total protein synthesis. No toxicity was noted with these treatments. Finally a
      possible effect of Ca2+ modulation on dPRL synthesis was studied using [35S]
      methionine. The specific activity of [35S] methionine on dPRL was similar in
      control and treated cells (EGTA, 2 mM Ca2+, cobalt). These results support the
      idea that Ca2+ controls dPRL synthesis in decidual cells, acting only on general
      protein synthesis processes.

PMID- 8570575
TI  - The maternal leucocyte response to the endometrial cups in horses is correlated
      with the developmental stages of the invasive trophoblast cells.
AB  - Invading trophoblasts form endometrial cups in the endometrium of the pregnant
      mare. In the present study we characterized the maternal leucocyte response to
      endometrial cups from their formation to their regression. The maternal leucocyte
      response was correlated with the stages of trophoblast development. (1)
      Aggregates of CD4+ and CD8+ cells were present between the migrating and
      differentiating endometrial cup trophoblasts and surrounding the forming
      endometrial cups. (2) Numbers of CD4+ cells within the mature endometrial cups
      were much reduced. At the periphery of the endometrial cups CD4+ and CD8+ cells
      were found in patchy accumulations around endometrial glands; small clusters of
      CD79+ B lymphocytes were present as well. (3) Scattered CD4+ and CD8+ cells were
      found within dying endometrial cups; areas of cell death were infiltrated with
      neutrophils. Large aggregates of CD4+ cells and CD8+ cells, and small but
      numerous clusters of CD79+ cells and eosinophils, were found outside of the dying
      endometrial cups. The CD4+ or CD8+ cells were mostly CD3+ T cells; some were
      probably macrophages which can express both of these markers in horses. The
      correlation between the developmental stages of the endometrial cup trophoblast
      and the maternal leucocyte response suggests a complicated cytokine-mediated
      regulatory network.

PMID- 8570576
TI  - Effects of PF1022A on adult Angiostrongylus cantonensis in the pulmonary arteries
      and larvae migrating into the central nervous system of rats.
AB  - We examined the effects of PF1022A, newly developing in Japan, on adult
      Angiostrongylus cantonensis in the pulmonary arteries of rats. Following five and
      ten successive oral doses at 10 mg/kg per day, the first-stage larvae in rat
      faeces disappeared completely at 2 weeks after treatment. The treatment
      completely killed the female worms, but not the male worms. However, numbers of
      male worms were also decreased after the administration of either five successive
      oral doses at 10 mg/kg per day for four courses or five successive
      intraperitoneal doses at 0.5 mg/kg per day. Next, we examined the effects of
      PF1022A on larval A. cantonensis migrating into the central nervous system (CNS)
      of rats. Following five successive oral doses at 5 or 10 mg/kg per day and five
      successive intraperitoneal doses at 0.5 mg/kg per day, lesser killing effects
      were observed on male as well as female worms. On the basis of these results it
      is apparent that PF1022A will become a promising anthelmintic available as
      treatment for tissue-dwelling as well as intestinal nematodes.

PMID- 8570577
TI  - Characterization and comparison of merozoite antigens of different Babesia canis
      isolates by serological and immunological investigations.
AB  - Merozoites of four Babesia canis isolates from Hungary, France, Africa, and Egypt
      were purified. Antigens were compared in an enzyme-linked immunosorbent assay
      (ELISA) and by immunoblotting. In the ELISA, antigen from the highly pathogenic
      isolate from Hungary showed the highest sensitivity for homologous and
      heterologous immune sera. This was confirmed by immunoblotting. Protein bands of
      the Hungarian isolate were strongly recognized by all B. canis immune sera,
      whereas the antigens from the other isolates showed only weak reactions with
      homologous and heterologous immune sera. Significant was a protein band of about
      12 kDa appearing in all pathogenic isolates from Hungary, France, and South
      Africa but not in the apathogenic Egyptian isolate. This protein band may
      determine the virulence. For serological tests, the B. canis isolate from Hungary
      seems to be the one most suitable for detection of even mild infections.

PMID- 8570578
TI  - Ultrastructural colocalization of phosphorylcholine and a phosphorylcholine
      associated epitope in first-stage larvae of Trichinella spiralis.
AB  - Although the presence of phosphorylcholine (PC) in Trichinella is well
      established, the structures of the TSL-4 antigens that bear this epitope are
      unknown. A subset of TSL-4 antigens (TSL-8 antigens) has been reported to be
      absent from the surface of first-stage T. spiralis larvae. We report experiments
      with a monoclonal antibody (mAb US2) developed in mice with a relative inability
      to produce antibodies to PC. In immunoblotting, mAb US2 and anti-PC mAb (BH8)
      showed apparently identical binding patterns. In addition, we used an immunogold
      double-labeling technique to study the anatomical distribution of the epitopes
      recognized by these mAbs; the results obtained indicate close colocalization of
      epitopes for BH8 and US2 in tissues of T. spiralis first-stage larvae. On the
      basis of these results, we suggest that US2 probably binds to all T. spiralis TSL
      4 antigens, including TSL-8 antigens. We also clarify some conflicting previous
      reports on the distribution of PC immunoreactivity in first-stage larvae of T.
      spiralis.

PMID- 8570579
TI  - Mating behaviour in mixed infections of Schistosoma haematobium and S. mattheei.
AB  - In mixed infections of Schistosoma haematobium and S. mattheei, homospecific and
      heterospecific pairs are formed, with a preponderance of homospecific pairs
      indicating the existence of a mate preference system. S. haematobium apparently
      exhibits a greater specific mate recognition system than does S. mattheei. In
      sequential infections when mice are exposed to S. mattheei 4 weeks after
      infection with S. haematobium, S. haematobium males are better at pairing with S.
      mattheei females than are S. mattheei males. Hence, genetic exchanges between S.
      haematobium and S. mattheei giving rise to viable hybrids poses the problem of
      the genetic identity of these species of schistosomes. The most important
      reproductive isolating mechanisms are definitive host specificity, S. haematobium
      being primarily a parasite of man, whereas S. mattheei is a parasite of domestic
      stock and wild ungulates, and the preference for homospecific pairings in
      simultaneous infections. In contrast, when S. haematobium is the older infection,
      S. haematobium males are better than S. mattheei males at pairing with females of
      either species. Hybridisation is the likely outcome of such interactions. The
      lack of viability of S. mattheei male X S. haematobium female indicates genetic
      differences between the two species. Occurrences of natural hybridisation between
      S. haematobium and S. mattheei may lead to a change in the response of the
      parasite to chemotherapeutic treatment.

PMID- 8570580
TI  - Toxoplasma gondii: redistribution of tachyzoite surface protein during host cell
      invasion and intracellular development.
AB  - Immunoperoxidase localisation of antigen at the electron microscope level
      confirms that parasite surface proteins, in association with membrane, are shed
      from the surface of the zoite on invasion, while varying amounts are also
      internalised. SAG 1 is stable on intracellular zoites for up to 48 h, although
      new protein is also synthesised. SAG1 is present on the surface of daughter
      zoites and is found throughout the infected cell in distinct vacuoles; these
      vacuoles represent either direct extensions of the parasitophorous vacuole or
      true export of parasite surface material. Conflicting reports exist concerning
      the presence of SAG1 on the developing intraphagosomal membrane (IPM) network
      immediately post-invasion (Sibley et al. 1986; Dubremetz et al. 1993). It is not
      known whether the molecule continues to be expressed during intracellular
      development. The current study follows the fate of SAG1 during invasion and over
      the first 48 h of parasite multiplication within the host cell, using pre- and
      postinvasion labeling techniques at the electron microscope level.

PMID- 8570581
TI  - Heterogeneity in the synthesis of alpha-macroglobulins in outbred Swiss albino
      mice acutely infected with Trypanosoma cruzi.
AB  - Alpha-Macroglobulins (AM) are protease inhibitors with important roles in
      inflammation and in immunomodulation that behave as acute-phase proteins in many
      experimental models. In the present work the levels of AM in the plasma of
      outbred Swiss albino mice acutely infected with Trypanosoma cruzi were studied.
      The results showed that increased levels of AM were present in the majority of
      the infected mice and that AM levels increased independently of the rise in
      parasitaemia. There was a high degree of heterogeneity in the intensity of the
      modulation of AM levels as well as in the kinetics of AM synthesis. This
      heterogeneity was related neither with the intensity of infection nor with the
      sex of the host. No correlation between AM levels and survival to the acute phase
      could be observed in the outbred mice. The consequence of such a heterogeneity is
      unclear, although AM as immunoregulatory molecules could play a role in the
      development of the symptoms of the chronic phase of Chagas' disease.

PMID- 8570582
TI  - Redescription of the male and first description of the female of Capillaria
      carioca Freitas et Lent, 1935 (Nematoda: Capillariidae), a parasite of the marine
      fish Sphoeroides testudineus.
AB  - A redescription of the male and the first description of the female of the
      intestinal nematode Capillaria carioca Freitas et Lent, 1935 are presented on the
      basis of specimens collected from the type host, the marine fish Sphoeroides
      testudineus (Linnaeus) (Teleostei, Tetraodontoidei), from the Lagoon of
      Yucalpeten in the northern coast of Yucatan (Gulf of Mexico), Mexico. This
      species is characterized by a well-sclerotized spicule and by the presence of two
      large ventrolateral lobe-like papillae on the male caudal end and, therefore, is
      assigned to the subgenus Neocapillaria Moravec, 1987. C. carioca is reported from
      Mexico for the first time.

PMID- 8570583
TI  - In vitro cultivation of Trypanosoma acomys: production of insect stages and
      bloodstream forms.
AB  - When Trypanosoma acomys bloodstream forms were cultivated at 37 degrees C in
      Schneider's Drosophila medium supplemented with 20% (v/v) heat-inactivated foetal
      calf serum (FCS), with Microtus agrestis embryonic fibroblasts in RPMI 1640
      medium supplemented with 20% FCS or in Baltz's medium supplemented with 10% FCS,
      the parasites transformed and largely remained as epimastigotes. Epimastigotes
      were also usually the commonest stage observed when the parasites were co
      cultivated with a mosquito cell line at 27 degrees C. However, if these cultures
      were initiated with the supernatant suspensions from fibroblast cultures that had
      been cryopreserved, trypomastigotes, including bloodstream-like forms, were the
      predominant stage for the first 4 days of culture. It is suggested that the
      glycerol supplement or the temperature changes stimulated this unusual
      morphogenesis. At 27 degrees C, T. acomys was incapable of multiplying and died
      when cultured in fresh Schneider's Drosophila medium supplemented with 20% FCS,
      but co-cultivation with the mosquito cell lines or cultivation in cell-free
      supernatants from 1-week-old mosquito cell cultures was successful at this
      temperature; most of the parasites multiplied as epimastigotes.

PMID- 8570584
TI  - Serotonin, reserpine, and motility in Mesocestoides tetrathyridia. An
      experimental spectrofluorometry and immunocytochemistry study.
AB  - The relationship between serotonin (5-HT) and motility in tetrathyridia of
      Mesocestoides vogae (syn. M. corti) was studied with the aid of reserpine.
      Reserpine decreases the content of 5-HT as measured spectrofluorometrically and
      immunocytochemically and, furthermore, inhibits the motility, thus indicating a
      connection between the two. The results support the hypothesis about 5-HT being
      an excitatory neurotransmitter of motor activity in M. vogue. New neuroanatomical
      details were revealed by immunocytochemical staining.

PMID- 8570585
TI  - Morphology and ultrastructure of the digestive gland of Bithynia siamensis
      goniomphalus (Prosobranchia: Bithyniidae) and alterations induced by infection
      with the liver fluke Opisthorchis viverrini (Trematoda: Digenea).
AB  - The morphology and ultrastructure of the digestive gland of Bithynia siamensis
      goniomphalus and its alteration by infection with Opisthorchis viverrini were
      investigated by light and electron microscopy. The digestive gland of B. s.
      goniomphalus was composed of three different cell types: digestive cells,
      excretory cells, and narrow cells. In infected animals the number of excretory
      cells increased dramatically. Cellular injury in digestive cells as well as in
      excretory cells following the infection could be observed at the ultrastructural
      level.

PMID- 8570586
TI  - Oral transmission of trypanosomes of the subgenus Herpetosoma from small mammals.
AB  - The rodents Microtus agrestis, Clethrionomys glareolus, Apodemus sylvaticus and
      white BK rats were given either a single intraperitoneal (i.p.) injection, an
      intragastric (i.g.) inoculation or an oral (p.o.) inoculation of the culture
      forms, including metacyclic trypomastigotes, of Trypanosoma microti, T. evotomys,
      T. grosi and T. lewisi, respectively. Similar levels of parasitaemia were
      produced by each of the three routes of infection, although the prepatent period
      was 3-5 days shorter in the case of the i.p.-injected animals. The oral
      inoculation of blood from mice infected with T. musculi into uninfected mice
      (outbred) and from rats infected with T. lewisi into uninfected BK rats produced
      parasitaemia after 6-8 days. This is the first report of the oral and i.g.
      transmission of T. microti, T. evotomys and T. grosi into their specific
      homologous hosts.

PMID- 8570587
TI  - Effects of sequence alignment on the phylogeny of Sarcocystis deduced from 18S
      rDNA sequences.
AB  - The family Sarcocystidae contains a wide variety of parasitic protozoa, some of
      which are important pathogens of livestock and humans. The taxonomic
      relationships between two of the genera in this family (Toxoplasma and
      Sarcocystis) have been debated for a number of years and remain controversial.
      Recent studies, from comparisons of 18S rDNA-sequence data, have suggested that
      Sarcocystis is paraphyletic, although a hypothesis supporting monophyly of
      Sarcocystis could not be rejected. The present study shows that the
      phylogenetically informative nucleotide positions within the 18S rDNA are
      primarily located in the regions that make up the helices in the secondary
      structure of the 18S rRNA. A phylogenetic analysis of 18S rDNA-sequence data
      aligned by secondary structure constraints, or a subset of the data corresponding
      to all nucleotides found in the helices, provide unambiguous evidence supporting
      monophyly of Sarcocystis.

PMID- 8570588
TI  - Actin isoforms in the parasitic nematode Haemonchus contortus.
AB  - Actin proteins in the parasitic nematode Haemonchus contortus were partially
      purified by a new method based on precipitation with podophyllotoxin and
      dimethylsulfoxide. Two-dimensional gel electrophoresis of partially purified
      actin proteins revealed differences in isoform composition between adults and
      third-stage larvae. The significance of this finding is possibly related to the
      existence of differential functional or developmental characteristics between
      these two life-cycle stages.

PMID- 8570589
TI  - Occurrence of blastocystis sp. in cattle in Aragon, northeastern Spain.
AB  - The occurrence of Blastocystis sp. in cattle is reported herein for the first
      time in Spain. Stool samples from 554 bovines ranging from 3 days old to adults
      collected from 30 cattle farms in Aragon (northeastern Spain) were concentrated
      by the formalin-ethyl acetate method and examined light microscopically for the
      presence of gastrointestinal parasites. Vacuolated cells of Blastocystis sp. was
      detected in fecal specimens from 10 calves (1.8%) aged from 7 weeks to 6 months.
      Infected calves were detected at 3 of the 30 farms surveyed (10%). Blastocystis
      sp. cells were rounded or oval, with a diameter ranging from 6.25 to 15 microns.
      Blastocystis infection in cattle was never correlated with diarrhea, although
      infection intensities were generally low.

PMID- 8570590
TI  - Heat-shock and stress response of the parasitic nematode Haemonchus contortus.
AB  - Before and after a stress treatment, larval stages and adult worms of Haemonchus
      contortus were tested for the induction and expression of heat-shock proteins
      (HSPs) using immunoblot analysis with HSP70-and HSP65-specific monoclonal
      antibodies. Stress treatment or heat shock did not alter the signals obtained
      with these antibodies, but the amount of HSP70 differed between the successive
      stages. In addition, the different stages were metabolically labeled with [35S]
      methionine during a temperature-shock or chemical treatment and proteins were
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).
      The shocks resulted in an altered protein pattern. New was the de novo expression
      of a 20-kDa protein of adult worms after anthelmintic treatment.

PMID- 8570591
TI  - An enzyme-linked immunosorbent assay for detecting anti-Echinostoma trivolvis
      (trematoda) IgG in experimentally infected ICR mice. Cross-reactivity with E.
      caproni.
AB  - An enzyme-linked immunosorbent assay (ELISA) utilizing surface glycocalyx
      membrane crude antigen of adult Echinostoma trivolvis was developed for the
      detection of circulating anti-E. trivolvis IgG in experimentally infected ICR
      mice. An antigen concentration of 10.0 micrograms/ml was used, and it was
      possible to detect anti-E. trivolvis IgG at a dilution of 1/3,200. On day 10
      postinfection (p.i.), all infected mice had anti-E. trivolvis IgG reactive with
      the surface glycocalyx antigen. The IgG level varied over a 40-day period,
      showing a time-dependent pattern with a peak on day 16 p.i. The results
      concerning reciprocal cross-reactivity indicate that adult E. trivolvis and E.
      caproni share at least some of the surface antigens and express species-specific
      antigenic determinants in ICR mice at similar, nonsignificantly (P = 0.76)
      different levels.

PMID- 8570592
TI  - Evolving virus plagues.

PMID- 8570593
TI  - Population dynamics of flaviviruses revealed by molecular phylogenies.
AB  - The phylogeny of 123 complete envelope gene sequences was reconstructed in order
      to understand the evolution of tick- and mosquito-borne flaviviruses. An analysis
      of phylogenetic tree structure reveals a continual and asymmetric branching
      process in the tick-borne flaviviruses, compared with an explosive radiation in
      the last 200 years in viruses transmitted by mosquitoes. The distinction between
      these two viral groups probably reflects differences in modes of dispersal,
      propagation, and changes in the size of host populations. The most serious
      implication of this work is that growing human populations are being exposed to
      an expanding range of increasingly diverse viral strains.

PMID- 8570594
TI  - Vision: From Photon to Perception. Colloquium papers. Irvine, California, May 20
      22, 1995.

PMID- 8570595
TI  - How photons start vision.
AB  - Recent studies have elucidated how the absorption of a photon in a rod or cone
      cell leads to the generation of the amplified neural signal that is transmitted
      to higher-order visual neurons. Photoexcited visual pigment activates the GTP
      binding protein transducin, which in turn stimulates cGMP phosphodiesterase. This
      enzyme hydrolyzes cGMP, allowing cGMP-gated cationic channels in the surface
      membrane to close, hyperpolarize the cell, and modulate transmitter release at
      the synaptic terminal. The kinetics of reactions in the cGMP cascade limit the
      temporal resolution of the visual system as a whole, while statistical
      fluctuations in the reactions limit the reliability of detection of dim light.
      Much interest now focuses on the processes that terminate the light response and
      dynamically regulate amplification in the cascade, causing the single photon
      response to be reproducible and allowing the cell to adapt in background light. A
      light-induced fall in the internal free Ca2+ concentration coordinates negative
      feedback control of amplification. The fall in Ca2+ stimulates resynthesis of
      cGMP, antagonizes rhodopsin's catalytic activity, and increases the affinity of
      the light-regulated cationic channel for cGMP. We are using physiological methods
      to study the molecular mechanisms that terminate the flash response and mediate
      adaptation. One approach is to observe transduction in truncated, dialyzed
      photoreceptor cells whose internal Ca2+ and nucleotide concentrations are under
      experimental control and to which exogenous proteins can be added. Another
      approach is to observe transduction in transgenic mouse rods in which specific
      proteins within the cascade are altered or deleted.

PMID- 8570596
TI  - Gain and kinetics of activation in the G-protein cascade of phototransduction.
AB  - The guanine nucleotide binding protein (G protein) cascade underlying
      phototransduction is one of the best understood of all signaling pathways. The
      diffusional interactions of the proteins underlying the cascade have been
      analyzed, both at a macroscopic level and also in terms of the stochastic nature
      of the molecular contacts. In response to a single activated rhodopsin (R*)
      formed as a result of a single photon hit, it can be shown that molecules of the
      G-protein transducin will be activated approximately linearly with time. This, in
      turn, will cause the number of activated molecules of the effector protein (the
      phosphodiesterase) also to increase linearly with time. These kinetics of protein
      activation provide an accurate description of the time course of the rising phase
      of the photoreceptor's electrical response over a wide range of flash
      intensities. Recent estimates indicate that at room temperature each R* triggers
      activation of the phosphodiesterase at a rate of 1000-2000 subunits.s-1. Now that
      a quantitative description of the activation steps in transduction has been
      obtained, perhaps the greatest challenge for the future is to provide a
      comprehensive description of the shutoff reactions, so that a complete account of
      the photoreceptor's response to light can be achieved.

PMID- 8570597
TI  - The biology of vision of Drosophila.
AB  - Phototransduction systems in vertebrates and invertebrates share a great deal of
      similarity in overall strategy but differ significantly in the underlying
      molecular machinery. Both are rhodopsin-based G protein-coupled signaling
      cascades displaying exquisite sensitivity and broad dynamic range. However, light
      activation of vertebrate photoreceptors leads to activation of a cGMP
      phosphodiesterase effector and the generation of a hyperpolarizing response. In
      contrast, activation of invertebrate photoreceptors, like Drosophila, leads to
      stimulation of phospholipase C and the generation of a depolarizing receptor
      potential. The comparative study of these two systems of phototransduction offers
      the opportunity to understand how similar biological problems may be solved by
      different molecular mechanisms of signal transduction. The study of this process
      in Drosophila, a system ideally suited to genetic and molecular manipulation,
      allows us to dissect the function and regulation of such a complex signaling
      cascade in its normal cellular environment. In this manuscript I review some of
      our recent findings and the strategies used to dissect this process.

PMID- 8570598
TI  - Primate photopigments and primate color vision.
AB  - The past 15 years have brought much progress in our understanding of several
      basic features of primate color vision. There has been particular success in
      cataloging the spectral properties of the cone photopigments found in retinas of
      a number of primate species and in elucidating the relationship between cone
      opsin genes and their photopigment products. Direct studies of color vision show
      that there are several modal patterns of color vision among groupings of
      primates: (i) Old World monkeys, apes, and humans all enjoy trichromatic color
      vision, although the former two groups do not seem prone to the polymorphic
      variations in color vision that are characteristic of people; (ii) most species
      of New World monkeys are highly polymorphic, with individual animals having any
      of several types of dichromatic or trichromatic color vision; (iii) less is known
      about color vision in prosimians, but evidence suggests that at least some
      diurnal species have dichromatic color vision; and (iv) some nocturnal primates
      may lack color vision completely. In many cases the photopigments and
      photopigment gene arrangements underlying these patterns have been revealed and,
      as a result, hints are emerging about the evolution of color vision among the
      primates.

PMID- 8570599
TI  - Circuitry for color coding in the primate retina.
AB  - Human color vision starts with the signals from three cone photoreceptor types,
      maximally sensitive to long (L-cone), middle (M-cone), and short (S-cone)
      wavelengths. Within the retina these signals combine in an antagonistic way to
      form red-green and blue-yellow spectral opponent pathways. In the classical model
      this antagonism is thought to arise from the convergence of cone type-specific
      excitatory and inhibitory inputs to retinal ganglion cells. The circuitry for
      spectral opponency is now being investigated using an in vitro preparation of the
      macaque monkey retina. Intracellular recording and staining has shown that blue
      ON/yellow-OFF opponent responses arise from a distinctive bistratified ganglion
      cell type. Surprisingly, this cone opponency appears to arise by dual excitatory
      cone bipolar cell inputs: an ON bipolar cell that contacts only S-cones and an
      OFF bipolar cell that contacts L- and M-cones. Red-green spectral opponency has
      long been linked to the midget ganglion cells, but an underlying mechanism
      remains unclear. For example, receptive field mapping argues for segregation of L
      and M-cone signals to the midget cell center and surround, but horizontal cell
      interneurons, believed to generate the inhibitory surround, lack opponency and
      cannot contribute selective L- or M-cone input to the midget cell surround. The
      solution to this color puzzle no doubt lies in the great diversity of cell types
      in the primate retina that still await discovery and analysis.

PMID- 8570600
TI  - Cell fate determination in the vertebrate retina.
AB  - In the vertebrate central nervous system, the retina has been a useful model for
      studies of cell fate determination. Recent results from studies conducted in
      vitro and in vivo suggest a model of retinal development in which both the
      progenitor cells and the environment change over time. The model is based upon
      the notion that the mitotic cells within the retina change in their response
      properties, or "competence", during development. These changes presage the
      ordered appearance of distinct cell types during development and appear to be
      necessary for the production of the distinct cell types. As the response
      properties of the cells change, so too do the environmental signals that the
      cells encounter. Together, intrinsic properties and extrinsic cues direct the
      choice of cell fate.

PMID- 8570601
TI  - Molecular biology of retinal ganglion cells.
AB  - Retinal ganglion cells are the output neurons that encode and transmit
      information from the eye to the brain. Their diverse physiologic and anatomic
      properties have been intensively studied and appear to account well for a number
      of psychophysical phenomena such as lateral inhibition and chromatic opponency.
      In this paper, we summarize our current view of retinal ganglion cell properties
      and pose a number of questions regarding underlying molecular mechanisms. As an
      example of one approach to understanding molecular mechanisms, we describe recent
      work on several POU domain transcription factors that are expressed in subsets of
      retinal ganglion cells and that appear to be involved in ganglion cell
      development.

PMID- 8570602
TI  - Emergence of order in visual system development.
AB  - Neural connections in the adult central nervous system are highly precise. In the
      visual system, retinal ganglion cells send their axons to target neurons in the
      lateral geniculate nucleus (LGN) in such a way that axons originating from the
      two eyes terminate in adjacent but nonoverlapping eye-specific layers. During
      development, however, inputs from the two eyes are intermixed, and the adult
      pattern emerges gradually as axons from the two eyes sort out to form the layers.
      Experiments indicate that the sorting-out process, even though it occurs in utero
      in higher mammals and always before vision, requires retinal ganglion cell
      signaling; blocking retinal ganglion cell action potentials with tetrodotoxin
      prevents the formation of the layers. These action potentials are endogenously
      generated by the ganglion cells, which fire spontaneously and synchronously with
      each other, generating "waves" of activity that travel across the retina. Calcium
      imaging of the retina shows that the ganglion cells undergo correlated calcium
      bursting to generate the waves and that amacrine cells also participate in the
      correlated activity patterns. Physiological recordings from LGN neurons in vitro
      indicate that the quasiperiodic activity generated by the retinal ganglion cells
      is transmitted across the synapse between ganglion cells to drive target LGN
      neurons. These observations suggest that (i) a neural circuit within the immature
      retina is responsible for generating specific spatiotemporal patterns of neural
      activity; (ii) spontaneous activity generated in the retina is propagated across
      central synapses; and (iii) even before the photoreceptors are present, nerve
      cell function is essential for correct wiring of the visual system during early
      development. Since spontaneously generated activity is known to be present
      elsewhere in the developing CNS, this process of activity-dependent wiring could
      be used throughout the nervous system to help refine early sets of neural
      connections into their highly precise adult patterns.

PMID- 8570603
TI  - Multineuronal codes in retinal signaling.
AB  - The visual world is presented to the brain through patterns of action potentials
      in the population of optic nerve fibers. Single-neuron recordings show that each
      retinal ganglion cell has a spatially restricted receptive field, a limited
      integration time, and a characteristic spectral sensitivity. Collectively, these
      response properties define the visual message conveyed by that neuron's action
      potentials. Since the size of the optic nerve is strictly constrained, one
      expects the retina to generate a highly efficient representation of the visual
      scene. By contrast, the receptive fields of nearby ganglion cells often overlap,
      suggesting great redundancy among the retinal output signals. Recent multineuron
      recordings may help resolve this paradox. They reveal concerted firing patterns
      among ganglion cells, in which small groups of nearby neurons fire synchronously
      with delays of only a few milliseconds. As there are many more such firing
      patterns than ganglion cells, such a distributed code might allow the retina to
      compress a large number of distinct visual messages into a small number of optic
      nerve fibers. This paper will review the evidence for a distributed coding scheme
      in the retinal output. The performance limits of such codes are analyzed with
      simple examples, illustrating that they allow a powerful trade-off between
      spatial and temporal resolution.

PMID- 8570604
TI  - Spatial integration and cortical dynamics.
AB  - Cells in adult primary visual cortex are capable of integrating information over
      much larger portions of the visual field than was originally thought. Moreover,
      their receptive field properties can be altered by the context within which local
      features are presented and by changes in visual experience. The substrate for
      both spatial integration and cortical plasticity is likely to be found in a
      plexus of long-range horizontal connections, formed by cortical pyramidal cells,
      which link cells within each cortical area over distances of 6-8 mm. The
      relationship between horizontal connections and cortical functional architecture
      suggests a role in visual segmentation and spatial integration. The distribution
      of lateral interactions within striate cortex was visualized with optical
      recording, and their functional consequences were explored by using comparable
      stimuli in human psychophysical experiments and in recordings from alert monkeys.
      They may represent the substrate for perceptual phenomena such as illusory
      contours, surface fill-in, and contour saliency. The dynamic nature of receptive
      field properties and cortical architecture has been seen over time scales ranging
      from seconds to months. One can induce a remapping of the topography of visual
      cortex by making focal binocular retinal lesions. Shorter-term plasticity of
      cortical receptive fields was observed following brief periods of visual
      stimulation. The mechanisms involved entailed, for the short-term changes,
      altering the effectiveness of existing cortical connections, and for the long
      term changes, sprouting of axon collaterals and synaptogenesis. The mutability of
      cortical function implies a continual process of calibration and normalization of
      the perception of visual attributes that is dependent on sensory experience
      throughout adulthood and might further represent the mechanism of perceptual
      learning.

PMID- 8570605
TI  - Computational models of cortical visual processing.
AB  - The visual responses of neurons in the cerebral cortex were first adequately
      characterized in the 1960s by D. H. Hubel and T. N. Wiesel [(1962) J. Physiol.
      (London) 160, 106-154; (1968) J. Physiol. (London) 195, 215-243] using
      qualitative analyses based on simple geometric visual targets. Over the past 30
      years, it has become common to consider the properties of these neurons by
      attempting to make formal descriptions of these transformations they execute on
      the visual image. Most such models have their roots in linear-systems approaches
      pioneered in the retina by C. Enroth-Cugell and J. R. Robson [(1966) J. Physiol.
      (London) 187, 517-552], but it is clear that purely linear models of cortical
      neurons are inadequate. We present two related models: one designed to account
      for the responses of simple cells in primary visual cortex (V1) and one designed
      to account for the responses of pattern direction selective cells in MT (or V5),
      an extrastriate visual area thought to be involved in the analysis of visual
      motion. These models share a common structure that operates in the same way on
      different kinds of input, and instantiate the widely held view that computational
      strategies are similar throughout the cerebral cortex. Implementations of these
      models for Macintosh microcomputers are available and can be used to explore the
      models' properties.

PMID- 8570606
TI  - Motion perception: seeing and deciding.
AB  - The primate visual system offers unprecedented opportunities for investigating
      the neural basis of cognition. Even the simplest visual discrimination task
      requires processing of sensory signals, formation of a decision, and
      orchestration of a motor response. With our extensive knowledge of the primate
      visual and oculomotor systems as a base, it is now possible to investigate the
      neural basis of simple visual decisions that link sensation to action. Here we
      describe an initial study of neural responses in the lateral intraparietal area
      (LIP) of the cerebral cortex while alert monkeys discriminated the direction of
      motion in a visual display. A subset of LIP neurons carried high-level signals
      that may comprise a neural correlate of the decision process in our task. These
      signals are neither sensory nor motor in the strictest sense; rather they appear
      to reflect integration of sensory signals toward a decision appropriate for
      guiding movement. If this ultimately proves to be the case, several fascinating
      issues in cognitive neuroscience will be brought under rigorous physiological
      scrutiny.

PMID- 8570607
TI  - Binocular visual surface perception.
AB  - Binocular disparity, the differential angular separation between pairs of image
      points in the two eyes, is the well-recognized basis for binocular distance
      perception. Without denying disparity's role in perceiving depth, we describe two
      perceptual phenomena, which indicate that a wider view of binocular vision is
      warranted. First, we show that disparity can play a critical role in two
      dimensional perception by determining whether separate image fragments should be
      grouped as part of a single surface or segregated as parts of separate surfaces.
      Second, we show that stereoscopic vision is not limited to the registration and
      interpretation of binocular disparity but that it relies on half-occluded points,
      visible to one eye and not the other, to determine the layout and transparency of
      surfaces. Because these half-visible points are coded by neurons carrying eye-of
      origin information, we suggest that the perception of these surface properties
      depends on neural activity available at visual cortical area V1.

PMID- 8570608
TI  - Cell cycling and patterned cell proliferation in the wing primordium of
      Drosophila.
AB  - The pattern of cell proliferation in the Drosophila imaginal wing primordium is
      spatially and temporally heterogeneous. Direct visualization of cells in S, G2,
      and mitosis phases of the cell cycle reveals several features invariant
      throughout development. The fraction of cells in the disc in the different cell
      cycle stages is constant, the majority remaining in G1. Cells in the different
      phases of the cell cycle mainly appear in small synchronic clusters that are
      nonclonally derived but result from changing local cell-cell interactions.
      Cluster synchronization occurs before S and in the G2/M phases. Rates of cell
      division are neither constant nor clonal features. Cell cycle progression is
      linear rather than concentric. Clusters appear throughout the disc but with
      symmetries related to presumptive wing patterns, compartment boundaries, and vein
      clonal restrictions.

PMID- 8570609
TI  - Interresidue hydrogen bonding in a peptide nucleic acid.RNA heteroduplex.
AB  - Previous molecular mechanics calculations suggest that strands of peptide nucleic
      acids (PNAs) and complementary oligonucleotides form antiparallel duplexes
      stabilized by interresidue hydrogen bonds. In the computed structures, the amide
      carbonyl oxygen nearest the nucleobase (O7') forms an interresidue hydrogen bond
      with the backbone amide proton of the following residue, (n + 1)H1'. Of the 10
      published two dimensional 1H NMR structures of a hexameric PNA.RNA heteroduplex.
      PNA(GAACTC).r(GAGUUC), 9 exhibit two to five potential interresidue hydrogen
      bonds. In our minimized average structure, created from the coordinates of these
      10 NMR structures, three of the five possible interresidue hydrogen bond sites
      within the PNA backbone display the carbonyl oxygen (O7') and the amide proton (n
      + 1)H1' distances and N1'-H1'-(n - 1)O7' angles optimal for hydrogen bond
      formation. The finding of these interresidue hydrogen bonds supports the results
      of our previous molecular mechanics calculations.

PMID- 8570610
TI  - Apoptosis induced in Jurkat cells by several agents is preceded by intracellular
      acidification.
AB  - We have previously shown that in neutrophils deprived of granulocyte colony
      stimulating factor, apoptosis is preceded by acidification and that the
      protection against apoptosis conferred on neutrophils by granulocyte colony
      stimulating factor is dependent upon delay of this acidification. To test the
      hypothesis that acidification could be a general feature of apoptosis, we
      examined intracellular pH changes in another cell line. Jurkat cells, a T
      lymphoblastoid line, were induced to undergo apoptosis with anti-Fas IgM,
      cycloheximide, or exposure to short-wavelength UV light. We found that
      acidification occurred in response to treatment with these agents and that
      acidification preceded DNA fragmentation. Jurkat cells were also found to possess
      an acid endonuclease that is active below pH 6.8, compatible with a possible role
      for this enzyme in chromatin digestion during apoptosis. Incubation of the cells
      with the bases imidazole or chloroquine during treatment with anti-Fas antibody
      or cycloheximide or after UV exposure decreased apoptosis as assessed by nuclear
      morphology and DNA content. The alkalinizing effect of imidazole and chloroquine
      was shown by the demonstration that the percentage of cells with an intracellular
      pH below 6.8 after treatment with anti-Fas antibody, cycloheximide, or UV was
      diminished in the presence of base as compared with similarly treated cells
      incubated in the absence of base. We conclude that acidification is an early
      event in programmed cell death and may be essential for genome destruction.

PMID- 8570611
TI  - Analysis of differential gene expression by display of 3' end restriction
      fragments of cDNAs.
AB  - We have developed an approach to study changes in gene expression by selective
      PCR amplification and display of 3' end restriction fragments of double-stranded
      cDNAs. This method produces highly consistent and reproducible patterns, can
      detect almost all mRNAs in a sample, and can resolve hidden differences such as
      bands that differ in their sequence but comigrate on a gel. Bands corresponding
      to known cDNAs move to predictable positions on the gel, making this a powerful
      approach to correlate gel patterns with cDNA data bases. Applying this method, we
      have examined differences in gene expression patterns during T-cell activation.
      Of a total of 700 bands that were evaluated in this study, as many as 3-4%
      represented mRNAs that are upregulated, while approximately 2% were down
      regulated within 4 hr of activation of Jurkat T cells. These and other results
      suggest that this approach is suitable for the systematic, expeditious, and
      nearly exhaustive elucidation of subtle changes in the patterns of gene
      expression in cells with altered physiologic states.

PMID- 8570612
TI  - Electrical currents associated with nucleotide transport by the reconstituted
      mitochondrial ADP/ATP carrier.
AB  - The electrophoretic export of ATP against the import of ADP in mitochondria
      bridges the intra- versus extramitochondrial ATP potential gap. Here we report
      that the electrical nature of the ADP/ATP exchange by the mitochondrial ADP/ATP
      carrier (AAC) can be directly studied by measuring the electrical currents via
      capacitive coupling of AAC-containing vesicles on a planar lipid membrane. The
      currents were induced by the rapid liberation of ATP or ADP with UV flash
      photolysis from caged nucleotides. Six different transport modes of the AAC were
      studied: heteroexchange with either ADP or ATP inside the vesicles, initiated by
      photolysis of caged ATP or ADP; homoexchange with ADPex/ADPin or ATPex/ATPin; and
      caged ADP or ATP with unloaded vesicles. The heteroexchange produced the largest
      currents with the longest duration in line with the electrical charge difference
      ATP4- versus ADP3-. Surprisingly, also in the homoexchange and with unloaded
      vesicles, small currents were measured with shorter duration. In all three modes
      with caged ATP, a negative charge moved into the vesicles and with caged ADP it
      moved out of the vesicles. All currents were completely inhibited by a mixture of
      the inhibitors of the AAC, carboxyatractyloside and hongkrekate, which proves
      that the currents are exclusively due to AAC function. The observed charge
      movements in the heteroexchange system agree with the prediction from transport
      studies in mitochondria and reconstituted vesicles. The unexpected charge
      movements in the homoexchange or unloaded systems are interpreted to reveal
      transmembrane rearrangements of charged sites in the AAC when occupied with ADP
      or ATP. The results also indicate that not only ATP4- but also ADP3- contribute,
      albeit in opposite direction, to the electrical nature of the ADP/ATP exchange,
      which is at variance with former conclusions from biochemical transport studies.
      These measurements open up new avenues of studying the electrical interactions of
      ADP and ATP with the AAC.

PMID- 8570613
TI  - The Chlorella hexose/H+ symporter is a useful selectable marker and biochemical
      reagent when expressed in Volvox.
AB  - The multicellular obligately photoautotrophic alga Volvox is composed of only two
      types of cells, somatic and reproductive. Therefore, Volvox provides the simplest
      model system for the study of multicellularity. Metabolic labeling experiments
      using radioactive precursors are crucial for the detection of stage- and cell
      type-specific proteins, glycoproteins, lipids, and carbohydrates. However, wild
      type Volvox lacks import systems for sugars or amino acids. To circumvent this
      problem, the hexose/H+ symporter (HUP1) gene from the unicellular alga Chlorella
      was placed under the control of the constitutive Volvox beta-tubulin promoter.
      The corresponding transgenic Volvox strain synthesized the sugar transporter in a
      functional state and was able to efficiently incorporate 14C from labeled glucose
      or glucosamine. Sensitivity toward the toxic glucose/mannose analogue 2-deoxy
      glucose increased by orders of magnitude in transformants. Thus we report the
      successful transformation of Volvox with a gene of heterologous origin. The
      chimeric gene may be selected for in either a positive or a negative manner,
      because transformants exhibit both prolonged survival in the dark in the presence
      of glucose and greatly increased sensitivity to the toxic sugar 2-deoxyglucose.
      The former trait may make the gene useful as a dominant selectable marker for use
      in transformation studies, whereas the latter trait may make it useful in
      development of a gene-targeting system.

PMID- 8570614
TI  - A family of transmembrane proteins with homology to the MET-hepatocyte growth
      factor receptor.
AB  - In hunting for unknown genes on the human X chromosome, we identified a cDNA in
      Xq28 encoding a transmembrane protein (SEX) of 1871 amino acids. SEX shares
      significant homology with the extracellular domain of the receptors encoded by
      the oncogenes MET, RON, and SEA [hepatocyte growth factor (HGF) receptor family].
      Further screenings of cDNA libraries identified three additional sequences
      closely related to SEX: these were named SEP, OCT, and NOV and were located on
      human chromosomes 3p, 1, and 3q, respectively. The proteins encoded by these
      genes contain large cytoplasmic domains characterized by a distinctive highly
      conserved sequence (SEX domain). Northern blot analysis revealed different
      expression of the SEX family of genes in fetal tissues, with SEX, OCT, and NOV
      predominantly expressed in brain, and SEP expressed at highest levels in kidney.
      In situ hybridization analysis revealed that SEX has a distinctive pattern of
      expression in the developing nervous system of the mouse, where it is found in
      postmitotic neurons from the first stages of neuronal differentiation (9.5 day
      postcoitus). The SEX protein (220 kDa) is glycosylated and exposed at the cell
      surface. Unlike the receptors of the HGF family, p220SEX, a MET-SEX chimera or a
      constitutively dimerized TPR-SEX does not show tyrosine kinase activity. These
      data define a gene family (SEX family) involved in the development of neural and
      epithelial tissues, which encodes putative receptors with unexpected enzymatic or
      binding properties.

PMID- 8570615
TI  - Disruption of RB/E2F-1 interaction by single point mutations in E2F-1 enhances S
      phase entry and apoptosis.
AB  - The retinoblastoma protein (RB) has been proposed to function as a negative
      regulator of cell proliferation by complexing with cellular proteins such as the
      transcription factor E2F. To study the biological consequences of the RB/E2F-1
      interaction, point mutants of E2F-1 which fail to bind to RB were isolated by
      using the yeast two-hybrid system. Sequence analysis revealed that within the
      minimal 18-amino acid peptide of E2F-1 required for RB binding, five residues,
      Tyr (position 411), Glu (419), and Asp-Leu-Phe (423-425), are critical. These
      amino acids are conserved among the known E2F family members. While mutation of
      any of these five amino acids abolished binding to RB, all mutants retained their
      full transactivation potential. Expression of mutated E2F-1, when compared with
      that of wild-type, significantly accelerated entry into S phase and subsequent
      apoptosis. These results provide direct genetic evidence for the biological
      significance of the RB/E2F interaction and strongly suggest that the interplay
      between RB and E2F is critical for proper cell cycle progression.

PMID- 8570616
TI  - Characterization of GMP-17, a granule membrane protein that moves to the plasma
      membrane of natural killer cells following target cell recognition.
AB  - Cytotoxic lymphocytes are characterized by their inclusion of cytoplasmic
      granules that fuse with the plasma membrane following target cell recognition. We
      previously identified a cytotoxic granule membrane protein designated p15-TIA-1
      that is immunochemically related to an RNA-recognition motif (RRM)-type RNA
      binding protein designated p40-TIA-1. Although it was suggested that p15-TIA-1
      might be derived from p40-T1A-1 by proteolysis, N-terminal amino acid sequencing
      of p15-TIA-1 immunoaffinity purified from a natural killer (NK) cell line by
      using monoclonal antibody (mAb) 2G9 revealed that p15-T1A-1 is identical to the
      deduced amino acid sequence of NKG7 and GIG-1, cDNAs isolated from NK cells and
      granulocyte-colony-stimulating factor-treated mononuclear cells, respectively.
      Epitope mapping revealed that mAb 2G9 recognizes the C terminus of p15-T1A-1 and
      p40-T1A-1. The deduced amino acid sequence of p15-T1A-1/NKG7/GIG-1 predicts that
      the protein possesses four transmembrane domains, and immuno-electron microscopy
      localizes the endogenous protein to the membranes of cytotoxic granules in NK
      cells. Given its subcellular localization, we propose to rename-this protein GMP
      17, for granule membrane protein of 17 kDa. Immunofluorescence microscopy of
      freshly isolated NK cells confirms this granular localization. Target cell
      induced NK cell degranulation results in translocation of GMP-17 from granules to
      the plasma membrane, suggesting a possible role for GMP-17 in regulating the
      effector function of lymphocytes and neutrophils.

PMID- 8570617
TI  - A high-resolution annotated physical map of the human chromosome 13q12-13 region
      containing the breast cancer susceptibility locus BRCA2.
AB  - Various types of physical mapping data were assembled by developing a set of
      computer programs (Integrated Mapping Package) to derive a detailed, annotated
      map of a 4-Mb region of human chromosome 13 that includes the BRCA2 locus. The
      final assembly consists of a yeast artificial chromosome (YAC) contig with 42
      members spanning the 13q12-13 region and aligned contigs of 399 cosmids
      established by cross-hybridization between the cosmids, which were selected from
      a chromosome 13-specific cosmid library using inter-Alu PCR probes from the YACs.
      The end sequences of 60 cosmids spaced nearly evenly across the map were used to
      generate sequence-tagged sites (STSs), which were mapped to the YACs by PCR. A
      contig framework was generated by STS content mapping, and the map was assembled
      on this scaffold. Additional annotation was provided by 72 expressed sequences
      and 10 genetic markers that were positioned on the map by hybridization to
      cosmids.

PMID- 8570618
TI  - An X chromosome-linked gene encoding a protein with characteristics of a rhoGAP
      predominantly expressed in hematopoietic cells.
AB  - An increasingly large number of proteins involved in signal transduction have
      been identified in recent years and shown to control different steps of cell
      survival, proliferation, and differentiation. Among the genes recently identified
      at the tip of the long arm of the human X chromosome, a novel gene, C1, encodes a
      protein that appears to represent a newly discovered member of the group of
      signaling proteins involved in regulation of the small GTP binding proteins of
      the ras superfamily. The protein encoded by C1, p115, is synthesized
      predominantly in cells of hematopoietic origin. It is characterized by two
      regions of similarity to motifs present in known proteins: GAP and SH3 homologous
      regions. Its localization in a narrow cytoplasmic region just below the plasma
      membrane and its inhibitory effect on stress fiber organization indicate that
      p115 may down regulate rho-like GTPases in hematopoietic cells.

PMID- 8570619
TI  - Human immunodeficiency virus type 1 infection alters chemokine beta peptide
      expression in human monocytes: implications for recruitment of leukocytes into
      brain and lymph nodes.
AB  - Two chemokine (chemoattractant cytokines) beta peptides, macrophage inflammatory
      proteins 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta), were induced in human
      monocyte cultures following infection with the human immunodeficiency virus type
      1 (HIV-1). Induction depended on productive viral infection: not only did the
      kinetics of MIP-1 peptide induction closely follow those of viral replication,
      but monocyte cultures inoculated with heat-inactivated virus or infected in the
      presence of AZT failed to produce these chemokine beta peptides. In addition, HIV
      infection markedly altered the pattern of beta chemokine expression elicited by
      tumor necrosis factor (TNF), itself a potent proinflammatory cytokine upregulated
      during the development of AIDS. Reverse transcription (RT)-PCR and RT-in situ PCR
      studies on brain tissue from patients with AIDS dementia demonstrated elevated
      MIP-1 alpha and MIP-1 beta mRNA expression relative to comparable samples from
      HIV-1-infected patients without dementia. Cells expressing chemokines in HIV-1
      infected brains were identified morphologically as microglia and astrocytes. As
      MIP-1 alpha and MIP-1 beta are potent chemoattractants for both monocytes and
      specific subpopulations of lymphocytes, this dysregulation of beta chemokine
      expression may influence the trafficking of leukocytes during HIV infection.
      These data, taken together, suggest a mechanism by which HIV-1-infected monocytes
      might recruit uninfected T cells and monocytes to sites of active viral
      replication or inflammation, notably the brain and lymph nodes.

PMID- 8570620
TI  - Male fetal progenitor cells persist in maternal blood for as long as 27 years
      postpartum.
AB  - Rare nucleated fetal cells circulate within maternal blood. Noninvasive prenatal
      diagnosis by isolation and genetic analysis of these cells is currently being
      undertaken. We sought to determine if genetic evidence existed for persistent
      circulation of fetal cells from prior pregnancies. Venous blood samples were
      obtained from 32 pregnant women and 8 nonpregnant women who had given birth to
      males 6 months to 27 years earlier. Mononuclear cells were sorted by flow
      cytometry using antibodies to CD antigens 3, 4, 5, 19, 23, 34, and 38. DNA within
      sorted cells, amplified by PCR for Y chromosome sequences, was considered
      predictive of a male fetus or evidence of persistent male fetal cells. In the 32
      pregnancies, male DNA was detected in 13 of 19 women carrying a male fetus. In 4
      of 13 pregnancies with female fetuses, male DNA was also detected. All of the 4
      women had prior pregnancies; 2 of the 4 had prior males and the other 2 had
      terminations of pregnancy. In 6 of the 8 nonpregnant women, male DNA was detected
      in CD34+CD38+ cells, even in a woman who had her last son 27 years prior to blood
      sampling. Our data demonstrate the continued maternal circulation of fetal CD34+
      or CD34+CD38+ cells from a prior pregnancy. The prolonged persistence of fetal
      progenitor cells may represent a human analogue of the microchimerism described
      in the mouse and may have significance in development of tolerance of the fetus.
      Pregnancy may thus establish a long-term, low-grade chimeric state in the human
      female.

PMID- 8570621
TI  - Antimycobacterial activities of antisense oligodeoxynucleotide phosphorothioates
      in drug-resistant strains.
AB  - Strains of Mycobacterium smegmatis, a mycobacterium which shares genetic
      sequences, grows more rapidly, and is nonpathogenic in man as compared with
      Mycobacterium tuberculosis, were utilized for the initial development of new
      antimycobacterial therapy. Drug-resistant strains of M. smegmatis which are known
      to arise in a manner identical to the emergence of drug-resistant strains of M.
      tuberculosis were isolated and utilized as models for the antimycobacterial
      activities of modified and unmodified oligodeoxynucleotide phosphorothioates in
      broth cultures. Under normal conditions, oligodeoxynucleotide phosphorothioates
      do not enter mycobacteria, and several strategies were successfully utilized to
      afford entry of oligonucleotides into the mycobacterial cells. One involved the
      presence of very low levels of ethambutol, which enables the entry of
      oligonucleotides into mycobacteria because of its induced alterations in the cell
      wall, and another involved the utilization of oligonucleotides covalently
      attached to a D-cycloserine molecule, whereby entry into the mycobacterial cell
      is achieved by a receptor-mediated process. Another low molecular weight,
      covalently attached ligand that enabled the entry and subsequent
      antimycobacterial activities of oligodeoxynucleotide phosphorothioates in the
      absence of a cell wall modifying reagent was biotin. Significant sequence
      specific growth inhibition of wild-type, as well as of drug-resistant, M.
      smegmatis was obtained by modified oligonucleotides complementary in sequence to
      a specific region of the mycobacterium aspartokinase (ask) gene when utilized in
      combinations with ethambutol (as compared to ethambutol alone) or as D
      cycloserine or biotin covalent adducts without the presence of any other
      cytotoxic or cytostatic agent.

PMID- 8570622
TI  - Pars triangularis asymmetry and language dominance.
AB  - The pars triangular is a portion of Broca's area. The convolutions that form the
      inferior and caudal extent of the pars triangularis include the anterior
      horizontal and anterior ascending rami of the sylvian fissure, respectively. To
      learn if there are anatomic asymmetries of the pars triangularis, these
      convolutions were measured on volumetric magnetic resonance imaging scans of 11
      patients who had undergone selective hemispheric anesthesia (Wada testing) to
      determine hemispheric speech and language lateralization. Of the 10 patients with
      language lateralized to the left hemisphere, 9 had a leftward asymmetry of the
      pars triangularis. The 1 patient with language lateralized to the right
      hemisphere had a significant rightward asymmetry of the pars triangularis. Our
      data suggest that asymmetries of the pars triangularis may be related to speech
      language lateralization.

PMID- 8570623
TI  - Channel behavior in a gamma-aminobutyrate transporter.
AB  - Current produced by a gamma-aminobutyrate (GABA) transporter stably transfected
      into a mammalian cell line was observed in cell-attached and excised membrane
      patches. When GABA was absent, a fraction of the transporters produced cation
      permeable channels. When GABA plus Na+ was on either side of the membrane, the
      majority of transporters produced a high-frequency current noise attributed to
      the movement of ions in an occluded pore.

PMID- 8570624
TI  - Targeted overexpression of androgen receptor with a liver-specific promoter in
      transgenic mice.
AB  - The rodent liver displays marked age- and sex-dependent changes in androgen
      sensitivity due to the sexually dimorphic and temporally programmed expression of
      the androgen receptor (AR) gene. We have altered this normal phenotype by
      constitutive overexpression of the rat AR transgene in the mouse liver by
      targeting it via the human phenylalanine hydroxylase (hPAH) gene promoter. These
      transgenic animals in their heterozygous state produce an approximately 30-fold
      higher level of the AR in the liver as compared with the nontransgenic control.
      Androgen inactivation via sulfonation of the hormone by dehydroepiandrosterone
      sulfotransferase (DST), an androgen-repressible enzyme, also contributes to the
      age- and sex-dependent regulation of hepatic androgen sensitivity. DST has a
      broad range of substrate specificity and is responsible for the age- and sex
      specific activation of certain polycyclic aromatic hepatocarcinogens as well, by
      converting them to electrophilic sulfonated derivatives. In the transgenic
      female, the hepatic expression of DST was approximately 4-fold lower than in
      normal females, a level comparable to that in normal males. The hPAH-AR mice will
      serve as a valuable model for studying the sex- and age-invariant expression of
      liver-specific genes, particularly those involved in the activation of
      environmental hepatocarcinogens such as the aromatic hydrocarbons.

PMID- 8570625
TI  - Crystallographic analysis of endogenous peptides associated with HLA-DR1 suggests
      a common, polyproline II-like conformation for bound peptides.
AB  - The structure of the human major histocompatibility complex (MHC) class II
      molecule HLA-DR1 derived from the human lymphoblastoid cell line LG-2 has been
      determined in a complex with the Staphylococcus aureus enterotoxin B
      superantigen. The HLA-DR1 molecule contains a mixture of endogenous peptides
      derived from cellular or serum proteins bound in the antigen-binding site, which
      copurify with the class II molecule. Continuous electron density for 13 amino
      acid residues is observed in the MHC peptide-binding site, suggesting that this
      is the core length of peptide that forms common interactions with the MHC
      molecule. Electron density is also observed for side chains of the endogenous
      peptides. The electron density corresponding to peptide side chains that interact
      with the DR1-binding site is more clearly defined than the electron density that
      extends out of the binding site. The regions of the endogenous peptides that
      interact with DRI are therefore either more restricted in conformation or
      sequence than the peptide side chains or amino acids that project out of the
      peptide-binding site. The hydrogen-bond interactions and conformation of a
      peptide model built into the electron density are similar to other HLA-DR-peptide
      structures. The bound peptides assume a regular conformation that is similar to a
      polyproline type II helix. The side-chain pockets and conserved asparagine
      residues of the DR1 molecule are well-positioned to interact with peptides in the
      polyproline type II conformation and may restrict the range of acceptable peptide
      conformations.

PMID- 8570626
TI  - Formation of mnemonic neuronal responses to visual paired associates in
      inferotemporal cortex is impaired by perirhinal and entorhinal lesions.
AB  - Functional roles of the cortical backward signal in long-term memory formation
      were studied in monkeys performing a visual pair-association task. Before the
      monkeys learned the task, the anterior commissure was transected, disconnecting
      the anterior temporal cortex of each hemisphere. After training with 12 pairs of
      pictures, single units were recorded from the inferotemporal cortex of the
      monkeys as the control. By injecting a grid of ibotenic acid, we unilaterally
      lesioned the entorhinal and perirhinal cortex, which provides massive direct and
      indirect backward projections ipsilaterally to the inferotemporal cortex. After
      the lesion, the monkeys fixated the cue stimulus normally, relearned the
      preoperatively learned set (set A), and learned a new set (set B) of paired
      associates. Then, single units were recorded from the same area as for the
      prelesion control. We found that (i) in spite of the lesion, the sampled neurons
      responded strongly and selectively to both the set A and set B patterns and (ii)
      the paired associates elicited significantly correlated responses in the control
      neurons before the lesion but not in the cells tested after the lesion, either
      for set A or set B stimuli. We conclude that the ability of inferotemporal
      neurons to represent association between picture pairs was lost after the lesion
      of entorhinal and perirhinal cortex, most likely through disruption of backward
      neural signals to the inferotemporal neurons, while the ability of the neurons to
      respond to a particular visual stimulus was left intact.

PMID- 8570627
TI  - Vascular variant of prion protein cerebral amyloidosis with tau-positive
      neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP.
AB  - Deposition of PrP amyloid in cerebral vessels in conjunction with neurofibrillary
      lesions is the neuropathologic hallmark of the dementia associated with a stop
      mutation at codon 145 of PRNP, the gene encoding the prion protein (PrP). In this
      disorder, the vascular amyloid in tissue sections and the approximately 7.5-kDa
      fragment extracted from amyloid are labeled by antibodies to epitopes located in
      the PrP sequence including amino acids 90-147. Amyloid-laden vessels are also
      labeled by antibodies against the C terminus, suggesting that PrP from the normal
      allele is involved in the pathologic process. Abundant neurofibrillary lesions
      are present in the cerebral gray matter. They are composed of paired helical
      filaments, are labeled with antibodies that recognize multiple phosphorylation
      sites in tau protein, and are similar to those observed in Alzheimer disease. A
      PrP cerebral amyloid angiopathy has not been reported in diseases caused by PRNP
      mutations or in human transmissible spongiform encephalopathies; we propose to
      name this phenotype PrP cerebral amyloid angiopathy (PrP-CAA).

PMID- 8570628
TI  - Prostate-specific membrane antigen is a hydrolase with substrate and
      pharmacologic characteristics of a neuropeptidase.
AB  - This report demonstrates that the investigational prostatic carcinoma marker
      known as the prostate-specific membrane antigen (PSM) possesses hydrolytic
      activity with the substrate and pharmacologic properties of the N-acetylated
      alpha-linked acidic dipeptidase (NAALADase). NAALADase is a membrane hydrolase
      that has been characterized in the mammalian nervous system on the basis of its
      catabolism of the neuropeptide N-acetylaspartylglutamate (NAAG) to yield
      glutamate and N-acetylaspartate and that has been hypothesized to influence
      glutamatergic signaling processes. The immunoscreening of a rat brain cDNA
      expression library with anti-NAALADase antisera identified a 1428-base partial
      cDNA that shares 86% sequence identity with 1428 bases of the human PSM cDNA
      [Israeli, R. S., Powell, C. T., Fair, W. R. & Heston, W.D.W. (1993) Cancer Res.
      53, 227-230]. A cDNA containing the entire PSM open reading frame was
      subsequently isolated by reverse transcription-PCR from the PSM-positive prostate
      carcinoma cell line LNCaP. Transient transfection of this cDNA into two NAALADase
      negative cell lines conferred NAAG-hydrolyzing activity that was inhibited by the
      NAALADase inhibitors quisqualic acid and beta-NAAG. Thus we demonstrate a PSM
      encoded function and identify a NAALADase-encoding cDNA. Northern analyses
      identify at least six transcripts that are variably expressed in NAALADase
      positive but not in NAALADase-negative rat tissues and human cell lines;
      therefore, PSM and/or related molecular species appear to account for NAAG
      hydrolysis in the nervous system. These results also raise questions about the
      role of PSM in both normal and pathologic prostate epithelial-cell function.

PMID- 8570629
TI  - Nuclease-resistant ribozymes decrease stromelysin mRNA levels in rabbit synovium
      following exogenous delivery to the knee joint.
AB  - Catalytic RNA molecules, or ribozymes, have generated significant interest as
      potential therapeutic agents for controlling gene expression. Although ribozymes
      have been shown to work in vitro and in cellular assays, there are no reports
      that demonstrate the efficacy of synthetic, stabilized ribozymes delivered in
      vivo. We are currently utilizing the rabbit model of interleukin 1-induced
      arthritis to assess the localization, stability, and efficacy of exogenous
      antistromelysin hammerhead ribozymes. The matrix metalloproteinase stromelysin is
      believed to be a key mediator in arthritic diseases. It seems likely therefore
      that inhibiting stromelysin would be a valid therapeutic approach for arthritis.
      We found that following intraarticular administration ribozymes were taken up by
      cells in the synovial lining, were stable in the synovium, and reduced synovial
      interleukin 1 alpha-induced stromelysin mRNA. This effect was demonstrated with
      ribozymes containing various chemical modifications that impart nuclease
      resistance and that recognize several distinct sites on the message.
      Catalytically inactive ribozymes were ineffective, thus suggesting a cleavage
      mediated mechanism of action. These results suggest that ribozymes may be useful
      in the treatment of arthritic diseases characterized by dysregulation of
      metalloproteinase expression.

PMID- 8570630
TI  - Integration of multiple repeats of geminiviral DNA into the nuclear genome of
      tobacco during evolution.
AB  - Integration of viral DNA into the host nuclear genome, although not unusual in
      bacterial and animal systems, has surprisingly not been reported for plants. We
      have discovered geminvirus-related DNA (GRD) sequences, in the form of distinct
      sets of multiple direct repeats comprising three related repeat classes, situated
      in a unique locus in the Nicotiana tabacum (tobacco) nuclear genome. The
      organization of these sequences is similar or identical in eight different
      tobacco cultivars we have examined. DNA sequence analysis reveals that each
      repeat has sequences most resembling those of the New World geminiviral DNA
      replication origin plus the adjacent AL1 gene, encoding the viral replication
      protein. We believe these GRD sequences originated quite recently in Nicotiana
      evolution through integration of geminiviral DNA by some combination of the
      processes of illegitimate recombination, amplification, deletions, and
      rearrangements. These events must have occurred in plant tissue that was
      subsequently able to contribute to meristematic tissue yielding gametes. GRD may
      have been retained in tobacco by selection or by random fixation in a small
      evolving population. Although we cannot detect transcription of these sequences,
      this does not exclude the possibility that they may originally have been
      expressed.

PMID- 8570632
TI  - Molecular markers reveal cryptic sex in the human pathogen Coccidioides immitis.
AB  - Coccidioides immitis, cause of a recent epidemic of "Valley fever" in California,
      is typical of many eukaryotic microbes in that mating and meiosis have yet to be
      reported, but it is not clear whether sex is truly absent or just cryptic. To
      find out, we have undertaken a population genetic study using PCR amplification,
      screening for single-strand conformation polymorphisms, and direct DNA sequencing
      to find molecular markers with nucleotide-level resolution. Both population
      genetic and phylogenetic analyses indicate that C. immitis is almost completely
      recombining. To our knowledge, this study is the first to find molecular evidence
      for recombination in a fungus for which no sexual stage has yet been described.
      These results motivate a directed search for mating and meiosis and illustrate
      the utility of single-strand conformation polymorphism and sequencing with
      arbitrary primer pairs in molecular population genetics.

PMID- 8570631
TI  - A gene encoding a mitogen-activated protein kinase kinase kinase is induced
      simultaneously with genes for a mitogen-activated protein kinase and an S6
      ribosomal protein kinase by touch, cold, and water stress in Arabidopsis
      thaliana.
AB  - We describe here the cloning and characterization of a cDNA encoding a protein
      kinase that has high sequence homology to members of the mitogen-activated
      protein kinase (MAPK) kinase kinase (MAPKKK or MEKK) family; this cDNA is named
      cATMEKKI (Arabidopsis thaliana MAP kinase or ERK kinase kinase 1). The catalytic
      domain of the putative ATMEKK1 protein shows approximately 40% identity with the
      amino acid sequences of the catalytic domains of MAPKKKs (such as Byr2 from
      Schizosaccharomyces pombe, Ste11 from Saccharomyces cerevisiae, Bck1 from S.
      cerevisiae, MEKK from mouse, and NPK1 from tobacco). In yeast cells that
      overexpress ATMEKK1, the protein kinase replaces Ste11 in responding to mating
      pheromone. In this study, the expression of three protein kinases was examined by
      Northern blot analyses: ATMEKK1 (structurally related to MAPKKK), ATMPK3
      (structurally related to MAPK), and ATPK19 (structurally related to ribosomal S6
      kinase). The mRNA levels of these three protein kinases increased markedly and
      simultaneously in response to touch, cold, and salinity stress. These results
      suggest that MAP kinase cascades, which are thought to respond to a variety of
      extracellular signals, are regulated not only at the posttranslational level but
      also at the transcriptional level in plants and that MAP kinase cascades in
      plants may function in transducing signals in the presence of environmental
      stress.

PMID- 8570633
TI  - Tissue-specific response of the human platelet-activating factor receptor gene to
      retinoic acid and thyroid hormone by alternative promoter usage.
AB  - We have studied the effects of retinoic acid (RA) and thyroid hormone (3,3',5
      triiodothyronine; T3) on platelet-activating factor receptor (PAFR) gene
      expression in intact rats and the ability of two human PAFR gene promoters (PAFR
      promoters 1 and 2) to generate two transcripts (PAFR transcripts 1 and 2).
      Northern blotting showed that RA and T3 regulated PAFR gene expression only in
      rat tissues that express PAFR transcript 2. Functional analysis of the human PAFR
      promoter 2 revealed that responsiveness to RA and T3 was conferred through a 24
      bp element [PAFR-hormone response element (HRE) located from -67 to -44 bp of the
      transcription start site, whereas PAFR promoter 1 did not respond to these
      hormones. The PAFR-HRE is composed of three direct repeated TGACCT-like hexamer
      motifs with 2-and 4-bp spaces, and the two upstream and two downstream motifs
      were identified as response elements for RA and T3. Thus, the PAF-PAFR pathway is
      regulated by the PAFR level altered by a tissue-specific response to RA and T3
      through the PAFR-HRE of the PAFR promoter 2.

PMID- 8570634
TI  - Z-DNA-forming sites within the human beta-globin gene cluster.
AB  - Agarose-encapsulated, metabolically active, permeabilized nuclei from human
      hematopoietic cell lines were tested for Z-DNA formation in the beta-globin gene
      cluster. Biotinylated monoclonal antibodies against Z-DNA were diffused into the
      nuclei and cross-linked to DNA with a 10-ns laser exposure at 266 nm. Following
      digestion with restriction enzymes, fragments that had formed Z-DNA were
      isolated. Seventeen regions with Z-DNA sequence motifs in the 73-kb region were
      studied by PCR amplification, and five were found in the Z conformation.

PMID- 8570635
TI  - Resolution of Holliday junctions by eukaryotic DNA topoisomerase I.
AB  - The Holliday junction, a key intermediate in both homologous and site-specific
      recombination, is generated by the reciprocal exchange of single strands between
      two DNA duplexes. Resolution of the junctions can occur in two directions with
      respect to flanking markers, either restoring the parental DNA configuration or
      generating a genetic crossover. Recombination can be regulated, in principle, by
      factors that influence the directionality of the resolution step. We demonstrate
      that the vaccinia virus DNA topoisomerase, a eukaryotic type I enzyme, catalyzes
      resolution of synthetic Holliday junctions in vitro. The mechanism entails
      concerted transesterifications at two recognition sites, 5'-CCCTT decreases, that
      are opposed within a partially mobile four-way junction. Cruciforms are resolved
      unidirectionally and with high efficiency into two linear duplexes. These
      findings suggest a model whereby type I topoisomerases may either promote or
      suppress genetic recombination in vivo.

PMID- 8570636
TI  - Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of
      transforming growth factor beta pathway components.
AB  - Although transforming growth factor beta (TGF-beta) superfamily ligands play
      critical roles in diverse developmental processes, how cells transduce signals
      from these ligands is still poorly understood. Cell surface receptors for these
      ligands have been identified, but their cytoplasmic targets are unknown. We have
      identified three Caenorhabditis elegans genes, sma-2, sma-3, and sma-4, that have
      mutant phenotypes similar to those of the TGF-beta-like receptor gene daf-4,
      indicating that they are required for daf-4-mediated developmental processes. We
      show that sma-2 functions in the same cells as daf-4, consistent with a role in
      transducing signals from the receptor. These three genes define a protein family,
      the dwarfins, that includes the Mad gene product, which participates in the
      decapentaplegic TGF-beta-like pathway in Drosophila [Sekelsky, J. J., Newfeld, S.
      J., Raftery, L. A., Chartoff, E. H. & Gelbart, W. M. (1995) Genetics 139, 1347
      1358]. The identification of homologous components of these pathways in distantly
      related organisms suggests that dwarfins may be universally required for TGF-beta
      like signal transduction. In fact, we have isolated highly conserved dwarfins
      from vertebrates, indicating that these components are not idiosyncratic to
      invertebrates. These analyses suggest that dwarfins are conserved cytoplasmic
      signal transducers.

PMID- 8570637
TI  - Heme oxygenase 2: endothelial and neuronal localization and role in endothelium
      dependent relaxation.
AB  - Heme oxygenase 2 (HO-2), which synthesizes carbon monoxide (CO), has been
      localized by immunohistochemistry to endothelial cells and adventitial nerves of
      blood vessels. HO-2 is also localized to neurons in autonomic ganglia, including
      the petrosal, superior cervical, and nodose ganglia, as well as ganglia in the
      myenteric plexus of the intestine. Enzyme studies demonstrated that tin
      protoporphyrin-9 is a selective inhibitor of HO with approximately 10-fold
      selectivity for HO over endothelial nitric oxide synthase (NOS) and soluble
      guanylyl cyclase. Inhibition of HO activity by tin protoporphyrin 9 reverses the
      component of endothelial-derived relaxation of porcine distal pulmonary arteries
      not reversed by an inhibitor of NOS. Thus, CO, like NO, may have endothelial
      derived relaxing activity. The similarity of NOS and HO-2 localizations and
      functions in blood vessels and the autonomic nervous system implies complementary
      and possibly coordinated physiologic roles for these two mediators.

PMID- 8570638
TI  - Toward antibody-directed "abzyme" prodrug therapy, ADAPT: carbamate prodrug
      activation by a catalytic antibody and its in vitro application to human tumor
      cell killing.
AB  - Antibody-directed enzyme prodrug therapy, ADEPT, is a recent approach to targeted
      cancer chemotherapy intended to diminish the nonspecific toxicity associated with
      many commonly used chemotherapeutic agents. Most ADEPT systems incorporate a
      bacterial enzyme, and thus their potential is reduced because of the
      immunogenicity of that component of the conjugate. This limitation can be
      circumvented by the use of a catalytic antibody, which can be "humanized," in
      place of the bacterial enzyme catalyst. We have explored the scope of such
      antibody-directed "abzyme" prodrug therapy, ADAPT, to evaluate the potential for
      a repeatable targeted cancer chemotherapy. We report the production of a
      catalytic antibody that can hydrolyze the carbamate prodrug 4-[N,N-bis(2
      chloroethyl)]aminophenyl-N-[(1S)-(1,3- dicarboxy)propyl]carbamate (1) to generate
      the corresponding cytotoxic nitrogen mustard (Km = 201 microM, kcat = 1.88 min
      1). In vitro studies with this abzyme, EA11-D7, and prodrug 1 lead to a marked
      reduction in viability of cultured human colonic carcinoma (LoVo) cells relative
      to appropriate controls. In addition, we have found a good correlation between
      antibody catalysis as determined by this cytotoxicity assay in vitro and
      competitive binding studies of candidate abzymes to the truncated transition
      state analogue ethyl 4-nitrophenylmethylphosphonate. This cell-kill assay heralds
      a general approach to direct and rapid screening of antibody libraries for
      catalysts.

PMID- 8570639
TI  - A combined kinetic and modeling study of the catalytic center subsites of human
      angiogenin.
AB  - Kinetic analysis and molecular modeling have been used to map the ribonucleolytic
      center of angiogenin (Ang). Pyrimidine nucleotides were found to interact very
      weakly with Ang, consistent with the inaccessible B1 pyrimidine binding site
      revealed by x-ray crystallography. Ang also lacks an effective phosphate binding
      site on the 5' side of B1. Although the B2 site that preferentially binds purines
      on the 3' side of B1 is also weak, its associated phosphate subsites make
      substantial contributions: both 3',5'-ADP and 5'-ADP have Ki values 6-fold lower
      than for 5'-AMP, and adding a 3'-phosphate to the substrate CpA increases Kcat/Km
      by 9-fold. Thus Ang has a functional P2 site on the 3' side of B2 and a site for
      a second phosphate on the 5' side of B2. Modeling of an Ang-d(ApTpApA) complex
      suggested that Arg-5 forms part of the P2 site and that a 2'-phosphate might bind
      more tightly than a 3'-phosphate. Both predictions were confirmed kinetically.
      The subsite map obtained by this combined approach indicated that 5'
      diphosphoadenosine 2'-phosphate might be a more potent inhibitor than any of the
      nucleotides tested thus far. Indeed, its Ki value of 150 microM is 50-fold lower
      than that for the best nucleotide previously reported and 400-fold lower than the
      Km for the best dinucleotide substrate. This compound may serve as a suitable
      starting point for the eventual design of tight-binding inhibitors of Ang as
      antiangiogenic agents for human therapy.

PMID- 8570640
TI  - Gangliosides are neuronal ligands for myelin-associated glycoprotein.
AB  - Nerve cells depend on specific interactions with glial cells for proper function.
      Myelinating glial cells are thought to associate with neuronal axons, in part,
      via the cell-surface adhesion protein, myelin-associated glycoprotein (MAG). MAG
      is also thought to be a major inhibitor of neurite outgrowth (axon regeneration)
      in the adult central nervous system. Primary structure and in vitro function
      place MAG in an immunoglobulin-related family of sialic acid-binding lactins. We
      report that a limited set of structurally related gangliosides, known to be
      expressed on myelinated neurons in vivo, are ligands for MAG. When major brain
      gangliosides were adsorbed as artificial membranes on plastic microwells, only
      GT1b and GD1a supported cell adhesion of MAG-transfected COS-1 cells.
      Furthermore, a quantitatively minor ganglioside expressed on cholinergic neurons,
      GQ1b alpha (also known as Chol-1 alpha-b), was much more potent than GT1b or GD1a
      in supporting MAG-mediated cell adhesion. Adhesion to either GT1b or GQ1b alpha
      was abolished by pretreatment of the adsorbed gangliosides with neuraminidase. On
      the basis of structure-function studies of 19 test glycosphingolipids, an alpha
      2,3-N-acetylneuraminic acid residue on the terminal galactose of a
      gangliotetraose core is necessary for MAG binding, and additional sialic acid
      residues linked to the other neutral core saccharides [Gal(II) and GalNAc(III)]
      contribute significantly to binding affinity. MAG-mediated adhesion to
      gangliosides was blocked by pretreatment of the MAG-transfected COS-1 cells with
      anti-MAG monoclonal antibody 513, which is known to inhibit oligodendrocyte
      neuron binding. These data are consistent with the conclusion that MAG-mediated
      cell-cell interactions involve MAG-ganglioside recognition and binding.

PMID- 8570641
TI  - DNA rearrangement mediated by inverted repeats.
AB  - Inverted repeats of DNA are widespread in the genomes of eukaryotes and
      prokaryotes and can mediate genome rearrangement. We studied rearrangement
      mediated by plasmid-borne inverted repeats in Escherichia coli. We show that
      inverted repeats can mediate an efficient and recA-independent recombination
      event. Surprisingly, the product of this recombination is not that of simple
      inversion between the inverted repeats, but almost exclusively an unusual head-to
      head dimer with complex DNA rearrangement. Moreover, this recombination is
      dramatically reduced by increasing the distance separating the repeats. These
      results can be readily explained by a model involving reciprocal switching of the
      leading and lagging strands of DNA replication within the inverted repeats, which
      leads to the formation of a Holliday junction. Reciprocal strand switching during
      DNA replication might be a common mechanism for genome rearrangement associated
      with inverted duplication.

PMID- 8570642
TI  - Endogenous c-src as a determinant of the tumorigenicity of src oncogenes.
AB  - We have compared the tumorigenicity of two src oncogenes, v-src and c-src(527),
      whose respective protein products pp60v-src and pp60c-src(527) show a different
      spectrum of amino acid substitutions vis-a-vis the c-src protooncogene-encoded
      product pp60c-src. Whereas the extent of primary tumor growth induced by c
      src(527) was quite similar in the two chicken lines tested, the extent of v-src
      induced tumor growth showed a marked line dependence. As examined with a line of
      chickens that shows immune-mediated regression of v-src-induced tumors, a weaker
      tumor immunity, as correlated with a greater level of primary tumor growth,
      resulted from inoculation of c-src(527) DNA than of v-src DNA. These observations
      indicated that the v-src-specific amino acid substitutions define a major tumor
      antigenicity. That a separate src-associated antigenicity is also targetable by
      the tumor immune response followed from the finding that the level of protective
      immunity against the growth of c-src(527) DNA-induced tumors was augmented under
      conditions of the prior regression of v-src DNA-induced tumors. As this latter
      antigenicity may include one or more c-src(527)-encoded peptides that are
      equivalent to c-src-encoded self peptides, these observations suggest that a host
      tolerance to pp60c-src can be broken so as to permit a tumor immune response
      based on recognition of self peptides of pp60c-src(527).

PMID- 8570643
TI  - In vivo examination of membrane protein localization and degradation with green
      fluorescent protein.
AB  - To test the utility of green fluorescent protein (GFP) as an in vivo reporter
      protein when fused to a membrane domain, we made a fusion protein between yeast
      hydroxymethylglutaryl-CoA reductase and GFP. Fusion proteins displayed spatial
      localization and regulated degradation consistent with the native
      hydroxymethylglutaryl-CoA reductase proteins. Thus, GFP should be useful in the
      study of both membrane protein localization and protein degradation in vivo.

PMID- 8570644
TI  - Involvement of Ras/Raf/AP-1 in BMP-4 signaling during Xenopus embryonic
      development.
AB  - Previously, we elucidated the role of bone morphogenetic protein 4 (BMP-4) in the
      dorsal-ventral patterning of the Xenopus embryo by using a dominant negative
      mutant of the BMP-4 receptor (DN-BR). The present paper describes the involvement
      of Ras, Raf, and activator protein 1 (AP-1) in BMP-4 signaling during Xenopus
      embryonic development. The AP-1 activity was determined by injecting an AP-1
      dependent luciferase reporter gene into two-cell-stage Xenopus embryos and
      measuring the luciferase activity at various developmental stages. We found that
      injection of BMP-4 mRNA increased AP-1 activity, whereas injection of DN-BR mRNA
      inhibited AP-1 activity. Similar inhibitory effects were seen with injection of
      mRNAs encoding dominant negative mutants of c-Ha-Ras, c-Raf, or c-Jun. These
      results suggest that the endogenous AP-1 activity is regulated by BMP
      4/Ras/Raf/Jun signals. We next investigated the effects of Ras/Raf/AP-1 signals
      on the biological functions of BMP-4. DN-BR-induced dorsalization of the embryo,
      revealed by the formation of a secondary body axis or dorsalization of the
      ventral mesoderm explant analyzed by histological and molecular criteria, was
      significantly reversed by coinjection of [Val12]Ha-Ras, c-Raf, or c-Jun mRNA.
      Furthermore, the BMP-4-stimulated erythroid differentiation in the ventral
      mesoderm was substantially inhibited by coinjection with the dominant negative c
      Ha-Ras, c-Raf, or c-Jun mutant. Our results suggest the involvement of Ras/Raf/AP
      1 in the BMP-4 signaling pathway.

PMID- 8570645
TI  - How the first biopolymers could have evolved.
AB  - In this work, we discuss a possible origin of the first biopolymers with stable
      unique structures. We suggest that at the prebiotic stage of evolution, long
      organic polymers had to be compact to avoid hydrolysis and had to be soluble and
      thus must not be exceedingly hydrophobic. We present an algorithm that generates
      such sequences for model proteins. The evolved sequences turn out to have a
      stable unique structure, into which they quickly fold. This result illustrates
      the idea that the unique three-dimensional native structures of first biopolymers
      could have evolved as a side effect of nonspecific physicochemical factors acting
      at the prebiotic stage of evolution.

PMID- 8570646
TI  - Preferential self-association of basic fibroblast growth factor is stabilized by
      heparin during receptor dimerization and activation.
AB  - Central to signaling by fibroblast growth factors (FGFs) is the oligomeric
      interaction of the growth factor and its high-affinity cell surface receptor,
      which is mediated by heparin-like polysaccharides. It has been proposed that the
      binding of heparin-like polysaccharides to FGF induces a conformational change in
      FGF, resulting in the formation of FGF dimers or oligomers, and this biologically
      active form is 'presented' to the FGF receptor for signal transduction. In this
      study, we show that monomeric basic FGF (FGF-2) preferentially self-associates
      and forms FGF-2 dimers and higher-order oligomers. As a consequence, FGF-2
      monomers are oriented for binding to heparin-like polysaccharides. We also show
      that heparin-like polysaccharides can readily bind to self-associated FGF-2
      without causing a conformational change in FGF-2 or disrupting the FGF-2 self
      association, but that the bound polysaccharides only additionally stabilize the
      FGF-2 self-association. The preferential self-association corresponds to FGF-2
      translations along two of the unit cell axes of the FGF-2 crystal structures.
      These two axes represent the two possible heparin binding directions, whereas the
      receptor binding sites are oriented along the third axis. Thus, we propose that
      preferential FGF-2 self-association, further stabilized by heparin, like "beads
      on a string," mediates FGF-2-induced receptor dimerization and activation. The
      observed FGF-2 self-association, modulated by heparin, not only provides a
      mechanism of growth factor activation but also represents a regulatory mechanism
      governing FGF-2 biological activity.

PMID- 8570647
TI  - An immunoglobulin mutator that targets G.C base pairs.
AB  - Hypermutation can be defined as an enhancement of the spontaneous mutation rate
      which the organism uses in certain types of differentiated cells where a high
      mutation rate is advantageous. At the immunoglobulin loci this process increases
      the mutation rate > 10(5)-fold over the normal, spontaneous rate. Its proximate
      cause is called the immunoglobulin mutator system. The most important function of
      this system is to improve antibody affinity in an ongoing response; it is turned
      on and off during the differentiation of B lymphocytes. We have established an in
      vitro system to study hypermutation by transfecting a rearranged mu gene into a
      cell line in which an immunoglobulin mutator has been demonstrated. A construct
      containing the mu gene and the 3' kappa enhancer has all the cis-acting elements
      necessary for hypermutation of the endogenous gene segments encoding the variable
      region. The activity of the mutator does not seem to depend strongly on the
      position of the transfected gene in the genome. The mutator is not active in
      transformed cells of a later differentiation stage. It is also not active on a
      transfected lacZ gene. These results are consistent with the specificity of the
      mutator system being maintained and make it possible to delineate cis and trans
      mutator elements in vitro. Surprisingly, the mutator preferentially targets G-C
      base pairs. Two hypotheses are discussed: (i) the immunoglobulin mutator system
      in mammals consists of several mutators, of which the mutator described here is
      only one; or (ii) the primary specificity of the system is biased toward mutation
      of G-C base pairs, but this specificity is obscured by antigenic selection.

PMID- 8570648
TI  - Arabidopsis MBP1 gene encodes a conserved ubiquitin recognition component of the
      26S proteasome.
AB  - Multiubiquitin chain attachment is a key step leading to the selective
      degradation of abnormal polypeptides and many important regulatory proteins by
      the eukaryotic 26S proteasome. However, the mechanism by which the 26S complex
      recognizes this posttranslational modification is unknown. Using synthetic
      multiubiquitin chains to probe an expression library for interacting proteins, we
      have isolated an Arabidopsis cDNA, designated MBP1, that encodes a 41-kDa acidic
      protein exhibiting high affinity for chains, especially those containing four or
      more ubiquitins. Based on similar physical and immunological properties,
      multiubiquitin binding affinities, and peptide sequence, MBP1 is homologous to
      subunit 5a of the human 26S proteasome. Structurally related proteins also exist
      in yeast, Caenorhabditis, and other plant species. Given their binding
      properties, association with the 26S proteasome, and widespread distribution,
      MBP1, S5a, and related proteins likely function as essential ubiquitin
      recognition components of the 26S proteasome.

PMID- 8570649
TI  - Surface hydrophobic residues of multiubiquitin chains essential for proteolytic
      targeting.
AB  - Ubiquitin conjugation is a signal for degradation of eukaryotic proteins by the
      26S protease. Conjugation of a homopolymeric multiubiquitin chain to a substrate
      lysine residue results in 10-fold faster degradation than does conjugation of
      monoubiquitin, but the molecular basis of enhanced targeting by chains is
      unknown. We show that ubiquitin residues L8, I44, and V70 are critical for
      targeting. Mutation of pairs of these residues to alanine had little effect on
      attachment of ubiquitin to substrates but severely inhibited degradation of the
      resulting conjugates. The same mutations blocked the binding of chains to a
      specific subunit (S5a) of the regulatory complex of the 26S protease. The side
      chains implicated in this binding--L8, I44, and V70--form repeating patches on
      the chain surface. Thus, hydrophobic interactions between these patches and S5a
      apparently contribute to enhanced proteolytic targeting by multiubiquitin chains.

PMID- 8570650
TI  - Null mutation of endothelin receptor type B gene in spotting lethal rats causes
      aganglionic megacolon and white coat color.
AB  - Mutations in the gene encoding the endothelin receptor type B (EDNRB) produce
      congenital aganglionic megacolon and pigment abnormalities in mice and humans.
      Here we report a naturally occurring null mutation of the EDNRB gene in spotting
      lethal (sl) rats, which exhibit aganglionic megacolon associated with white coat
      color. We found a 301-bp deletion spanning the exon 1-intron 1 junction of the
      EDNRB gene in sl rats. A restriction fragment length polymorphism caused by this
      deletion perfectly cosegregates with the sl phenotype. The deletion leads to
      production of an aberrantly spliced EDNRB mRNA that lacks the coding sequence for
      the first and second putative transmembrane domains of the G-protein-coupled
      receptor. Radioligand binding assays revealed undetectable levels of functional
      EDNRB in tissues from homozygous sl/sl rats. We conclude that EDNRB plays an
      essential role in the normal development of two neural crest-derived cell
      lineages, epidermal melanocytes and enteric neurons, in three mammalian species-
      humans, mice, and rats. The EDNRB-deficient rat may also prove valuable in
      defining the postnatal physiologic role of this receptor.

PMID- 8570651
TI  - Transcriptional activation of the mouse obese (ob) gene by CCAAT/enhancer binding
      protein alpha.
AB  - Like other adipocyte genes that are transcriptionally activated by CCAAT/enhancer
      binding protein alpha (C/EBP alpha) during preadipocyte differentiation,
      expression of the mouse obese (ob) gene is immediately preceded by the expression
      of C/EBP alpha. While the 5' flanking region of the mouse ob gene contains
      several consensus C/EBP binding sites, only one of these sites appears to be
      functional. DNase I cleavage inhibition patterns (footprinting) of the ob gene
      promoter revealed that recombinant C/EBP alpha, as well as a nuclear factor
      present in fully differentiated 3T3-L1 adipocytes, but present at a much lower
      level in preadipocytes, protects the same region between nucleotides -58 and -42
      relative to the transcriptional start site. Electrophoretic mobility-shift
      analysis using nuclear extracts from adipose tissue or 3T3-L1 adipocytes and an
      oligonucleotide probe corresponding to a consensus C/EBP binding site at
      nucleotides -55 to -47 generated a specific protein-oligonucleotide complex that
      was supershifted by antibody against C/EBP alpha. Probes corresponding to two
      upstream consensus C/EBP binding sites failed to generate protein-oligonucleotide
      complexes. Cotransfection of a C/EBP alpha expression vector into 3T3-L1 cells
      with a series of 5' truncated ob gene promoter constructs activated reporter gene
      expression with all constructs containing the proximal C/EBP binding site
      (nucleotides -55 to -47). Mutation of this site blocked transactivation by C/EBP
      alpha. Taken together, these findings implicate C/EBP alpha as a transcriptional
      activator of the ob gene promoter and identify the functional C/EBP binding site
      in the promoter.

PMID- 8570652
TI  - Three-dimensional structure of recombinant human osteogenic protein 1: structural
      paradigm for the transforming growth factor beta superfamily.
AB  - We report the three-dimensional structure of osteogenic protein 1 (OP-1, also
      known as bone morphogenetic protein 7) to 2.8-A resolution. OP-1 is a member of
      the transforming growth factor beta (TGF-beta) superfamily of proteins and is
      able to induce new bone formation in vivo. Members of this superfamily share
      sequence similarity in their C-terminal regions and are implicated in embryonic
      development and adult tissue repair. Our crystal structure makes possible the
      structural comparison between two members of the TGF-beta superfamily. We find
      that although there is limited sequence identity between OP-1 and TGF-beta 2,
      they share a common polypeptide fold. These results establish a basis for
      proposing the OP-1/TGF-beta 2 fold as the primary structural motif for the TGF
      beta superfamily as a whole. Detailed comparison of the OP-1 and TGF-beta 2
      structures has revealed striking differences that provide insights into how these
      growth factors interact with their receptors.

PMID- 8570653
TI  - The chromosomal distribution of mouse odorant receptor genes.
AB  - Odorant receptors (ORs) on nasal olfactory sensory neurons are encoded by a large
      multigene family. Each member of the family is expressed in a small percentage of
      neurons that are confined to one of several spatial zones in the nose but are
      randomly distributed throughout that zone. This pattern of expression suggests
      that when the sensory neuron selects which OR gene to express it may be confined
      to a particular zonal gene set of several hundred OR genes but select from among
      the members of that set via a stochastic mechanism. Both locus-dependent and
      locus-independent models of OR gene choice have been proposed. To investigate the
      feasibility of these models, we determined the chromosomal locations of 21 OR
      genes expressed in four different spatial zones. We found that OR genes are
      clustered within multiple loci that are broadly distributed in the genome. These
      loci lie within paralogous chromosomal regions that appear to have arisen by
      duplications of large chromosomal domains followed by extensive gene duplication
      and divergence. Our studies show that OR genes expressed in the same zone map to
      numerous loci; moreover, a single locus can contain genes expressed in different
      zones. These findings raise the possibility that OR gene choice may be locus
      independent or involve consecutive stochastic choices.

PMID- 8570654
TI  - Real time measurements of elongation by a reverse transcriptase using surface
      plasmon resonance.
AB  - A rapid direct assay for polymerase-induced elongation along a given template is
      an obligate requirement for understanding the processivity of polymerization and
      the mode of action of drugs and inhibitors on this process. Surface plasmon
      resonance can be used to follow the association and the dissociation rates of a
      given reverse transcriptase on DNA.RNA and DNA.DNA hybrids immobilized on a
      biotin-streptavidin surface. The addition of nucleotides complementary to the
      template strand produces an increase in the local mass, as deduced from an
      increase in the measured signal, due to elongation of the primer strand that
      allows an estimation of both the extent and rate of the polymerization process.
      The terminator drug 3'-deoxy-3'-azidothymidine triphosphate completely abolishes
      the increase in signal as would be expected from an inhibition of elongation.
      This technique provides a sensitive assay for the affinities of different
      polymerases for specific templates and for the effects of terminators of the
      elongation process.

PMID- 8570655
TI  - Transcriptional activation of the human proliferating-cell nuclear antigen
      promoter by p53.
AB  - Proliferating-cell nuclear antigen (PCNA) is a DNA damage-inducible protein that
      performs an essential function in DNA replication and repair as an auxiliary
      factor for DNA polymerases delta and epsilon. Examination of the human PCNA
      promoter DNA sequence revealed a site with homology to the consensus DNA sequence
      bound by p53. PCNA promoter fragments with this site intact bound p53 in vitro
      and were transcriptionally activated by wild-type p53 in transient expression
      assays in SAOS-2 cells. The resident p53-binding site could be functionally
      substituted by a previously described p53-binding site from the ribosomal gene
      cluster. A plasmid expressing a mutated version of p53 derived from a patient
      with Li-Fraumeni syndrome failed to activate the PCNA promoter in the
      cotransfection assay. In different cell types, activation of the PCNA promoter by
      the p53-binding sequence correlated with the status of p53. Activation of the
      PCNA promoter by wild-type p53 depends upon the level of p53 expression. This
      concentration dependence and cell type specificity reconciles the observations
      presented here with prior results indicating that wild-type p53 represses the
      PCNA promoter. These findings provide a mechanism whereby p53 modulates
      activation of PCNA expression as a cellular response to DNA damage.

PMID- 8570656
TI  - Restricted expression of homeobox genes distinguishes fetal from adult human
      smooth muscle cells.
AB  - Smooth muscle cell plasticity is considered a prerequisite for atherosclerosis
      and restenosis following angioplasty and bypass surgery. Identification of
      transcription factors that specify one smooth muscle cell phenotype over another
      therefore may be of major importance in understanding the molecular basis of
      these vascular disorders. Homeobox genes exemplify one class of transcription
      factors that could govern smooth muscle cell phenotypic diversity. Accordingly,
      we screened adult and fetal human smooth muscle cell cDNA libraries with a
      degenerate oligonucleotide corresponding to a highly conserved region of the
      homeodomain with the idea that homeobox genes, if present, would display a smooth
      muscle cell phenotype-dependent pattern of expression. No homeobox genes were
      detected in the adult human smooth muscle cell library; however, five
      nonparalogous homeobox genes were uncovered from the fetal library (HoxA5,
      HoxA11, HoxB1, HoxB7, and HoxC9). Northern blotting of adult and fetal tissues
      revealed low and restricted expression of all five homeobox genes. No significant
      differences in transcripts of HoxA5, HoxA11, and HoxB1 were detected between
      adult or fetal human smooth muscle cells in culture. HoxB7 and HoxC9, however,
      showed preferential mRNA expression in fetal human smooth muscle cells that
      appeared to correlate with the age of the donor. This phenotype-dependent
      expression of homeobox genes was also noted in rat pup versus adult smooth muscle
      cells. While similar differences in gene expression have been reported between
      subsets of smooth muscle cells from rat vessels of different-aged animals or
      clones of rat smooth muscle, our findings represent a demonstration of a
      transcription factor distinguishing two human smooth muscle cell phenotypes.

PMID- 8570657
TI  - Muller's ratchet decreases fitness of a DNA-based microbe.
AB  - Muller proposed that an asexual organism will inevitably accumulate deleterious
      mutations, resulting in an increase of the mutational load and an inexorable,
      ratchet-like, loss of the least mutated class [Muller, H.J. (1964) Mutat. Res. 1,
      2-9]. The operation of Muller's ratchet on real populations has been
      experimentally demonstrated only in RNA viruses. However, these cases are
      exceptional in that the mutation rates of the RNA viruses are extremely high. We
      have examined whether Muller's ratchet operates in Salmonella typhimurium, a DNA
      based organism with a more typical genomic mutation rate. Cells were grown
      asexually under conditions expected to result in high genetic drift, and the
      increase in mutational load was determined. S. typhimurium accumulated mutations
      under these conditions such that after 1700 generations, 1% of the 444 lineages
      tested had suffered an obvious loss of fitness, as determined by decreased growth
      rate. These results suggest that in the absence of sex and with high genetic
      drift, genetic mechanisms, such as back or compensatory mutations, cannot
      compensate for the accumulation of deleterious mutations. In addition, we
      measured the appearance of auxotrophs, which allowed us to calculate an average
      spontaneous mutation rate of approximately 0.3-1.5 x 10(-9) mutations per base
      pair per generation. This rate is measured for the largest genetic target studied
      so far, a collection of about 200 genes.

PMID- 8570658
TI  - Significant competitive advantage conferred by meiosis and syngamy in the yeast
      Saccharomyces cerevisiae.
AB  - The presumed advantages of genetic recombinations are difficult to demonstrate
      directly. To investigate the effects of recombination and background
      heterozygosity on competitive ability, we have performed serial-transfer
      competition experiments between isogenic sexual and asexual strains of the yeast
      Saccharomyces cerevisiae. The members of these diploid pairs of strains differed
      only in being heterozygous (sexual) or homozygous (asexual) at the mating type or
      MAT locus. Competing pairs had either a completely homozygous or a heterozygous
      genetic background, the latter being heterozygous at many different loci
      throughout the genome. A round of meiotic recombination (automixis) conferred a
      large and statistically significant enhancement of competitive ability on sexual
      strains with a heterozygous genetic background. By contrast, in homozygous
      background competitions, meiosis decreased the sexual strains' initial relative
      competitive ability. In all cases, however, the sexual strains outcompeted their
      isogenic asexual counterparts, whether meiotic recombination had occurred or not.
      In some genetic backgrounds, this was due in part to an overdominance effect on
      competitive advantage of heterozygosity at the MAT locus. The advantage of the
      sexual strains also increased significantly during the course of the homozygous
      background competitions, particularly when meiosis had occurred. This latter
      effect either did not occur or was very weak in heterozygous background
      competitions. Overall, sexual strains with heterozygous genetic backgrounds had a
      significantly higher initial relative competitive ability than those with
      homozygous backgrounds. The advantage of mating type heterozygosity in this
      organism extends far beyond the ability to recombine meiotically.

PMID- 8570659
TI  - Localization of the mouse gene releasing sex-limited expression of Slp.
AB  - To probe genetic variation in the regulation of sexual dimorphism, we have
      characterized the mouse protein Slp, coded by the gene sex-limited protein (Slp).
      Slp expression in many strains is limited to males and is androgen-dependent.
      However, female expression is also observed in rare strains, due to nonlinked
      gene(s) termed regulator of sex-limitation (rsl). In this report we demonstrate
      that female expression of Slp results from homozygous recessive allele(s) at a
      single autosomal locus that maps to a 2.2-centimorgan interval on chromosome 13.
      This conclusion was supported by extensive genetic analyses including the use of
      polymorphic microsatellites to type numerous backcross progeny and a recombinant
      inbred series and to identify the congenic interval in three independently
      derived congenic strains. Four attractive candidate genes were identified by the
      localization of rsl. Interestingly, rsl was found not only to enable expression
      in females but to also increase expression in males. The findings suggest that
      the expression of Slp and perhaps other sexually dimorphic proteins is regulated
      by two pathways, one that is dependent upon rsl but not androgens and another
      that is rsl-independent but requires androgens.

PMID- 8570660
TI  - Fate of biological control introductions: monitoring an Australian fungal
      pathogen of grasshoppers in North America.
AB  - In North America there are two generally recognized pathotypes (pathotypes 1 and
      2) of the fungus Entomophaga grylli which show host-preferential infection of
      grasshopper subfamilies. Pathotype 3, discovered in Australia, has a broader
      grasshopper host range and was considered to be a good biocontrol agent. Between
      1989 and 1991 pathotype 3 was introduced at two field sites in North Dakota.
      Since resting spores are morphologically indistinguishable among pathotypes, we
      used pathotype-specific DNA probes to confirm pathotype identification in E.
      grylli-infected grasshoppers collected at the release sites in 1992, 1993, and
      1994. In 1992, up to 23% of E. grylli-infected grasshoppers of the subfamilies
      Melanoplinae, Oedipodinae, and Gomphocerinae were infected by pathotype 3, with
      no infections > 1 km from the release sites. In 1993, pathotype 3 infections
      declined to 1.7%. In 1994 grasshopper populations were low and no pathotype 3
      infections were found. The frequency of pathotype 3 infection has declined to
      levels where its long-term survival in North America is questionable. Analyses of
      biocontrol releases are critical to evaluating the environmental risks associated
      with these ecological manipulations, and molecular probes are powerful tools for
      monitoring biocontrol releases.

PMID- 8570661
TI  - Face encoding and recognition in the human brain.
AB  - A dissociation between human neural systems that participate in the encoding and
      later recognition of new memories for faces was demonstrated by measuring memory
      task-related changes in regional cerebral blood flow with positron emission
      tomography. There was almost no overlap between the brain structures associated
      with these memory functions. A region in the right hippocampus and adjacent
      cortex was activated during memory encoding but not during recognition. The most
      striking finding in neocortex was the lateralization of prefrontal participation.
      Encoding activated left prefrontal cortex, whereas recognition activated right
      prefrontal cortex. These results indicate that the hippocampus and adjacent
      cortex participate in memory function primarily at the time of new memory
      encoding. Moreover, face recognition is not mediated simply by recapitulation of
      operations performed at the time of encoding but, rather, involves anatomically
      dissociable operations.

PMID- 8570662
TI  - Intracerebral injection of human immunodeficiency virus type 1 coat protein gp120
      differentially affects the expression of nerve growth factor and nitric oxide
      synthase in the hippocampus of rat.
AB  - We have studied the neuropathological characteristics of the brain of rats
      receiving daily intracerebroventricular administration of freshly dissolved human
      immunodeficiency virus type 1 recombinant protein gp120 (100 ng per rat per day)
      given for up to 14 days. Histological examination of serial brain sections
      revealed no apparent gross damage to the cortex or hippocampus, nor did cell
      counting yield significant neuronal cell loss. However, the viral protein caused
      after 7 and 14 days of treatment DNA fragmentation in 10% of brain cortical
      neurons. Interestingly, reduced neuronal nitric oxide synthase (NOS) expression
      along with significant increases in nerve growth factor (NGF) were observed in
      the hippocampus, where gp120 did not cause neuronal damage. No changes in NGF and
      NOS expression were seen in the cortex, where cell death is likely to be of the
      apoptotic type. The present data demonstrate that gp120-induced cortical cell
      death is associated with the lack of increase of NGF in the cerebral cortex and
      suggest that the latter may be important for the expression of neuropathology in
      the rat brain. By contrast, enhanced levels of NGF may prevent or delay neuronal
      death in the hippocampus, where reduced NOS expression may be a reflection of a
      subcellular insult inflicted by the viral protein.

PMID- 8570663
TI  - Manipulation and potentiation of antimycobacterial immunity using recombinant
      bacille Calmette-Guerin strains that secrete cytokines.
AB  - Bacille Calmette-Guerin (BCG) is a live, attenuated strain of Mycobacterium bovis
      used widely for tuberculosis prophylaxis and bladder cancer immunotherapy,
      although it has limitations in both contexts. To investigate whether BCG's
      immunostimulatory properties could be modified, and to gain insight into the
      interaction between mycobacteria and their hosts, we constructed recombinant BCG
      strains that secrete functional murine cytokines and studied their properties in
      mouse models of experimental infection. Cell-mediated immune responses to
      mycobacterial antigen (purified protein derivative) were assayed using
      splenocytes from mice inoculated with various BCG recombinants. Antigen-specific
      proliferation and cytokine release were found to be substantially greater with
      splenocytes derived from mice injected with cytokine-secreting BCG than with
      splenocytes from mice injected with BCG lacking cytokines. The most profound
      effects were induced by BCG secreting interleukin 2, interferon gamma, or
      granulocyte-macrophage colony-stimulating factor. Thus, cytokine-secreting BCG
      can enhance immune responses to mycobacterial antigens and may be improved
      reagents for tuberculosis prophylaxis and cancer immunotherapy.

PMID- 8570664
TI  - Sequence-selective carbohydrate-DNA interaction: dimeric and monomeric forms of
      the calicheamicin oligosaccharide interfere with transcription factor function.
AB  - The synthetic oligosaccharide moiety of the antibiotic calicheamicin and the head
      to-head dimer of this oligosaccharide are known to bind to the minor groove of
      DNA in a sequence-selective manner preferring distinct target sequences. We
      tested these carbohydrates for their ability to interfere with transcription
      factor function. The oligosaccharides inhibit binding of transcription factors to
      DNA in a sequence-selective manner, probably by inducing a conformational change
      in DNA structure. They also interfere with transcription by polymerase II in
      vitro. The effective concentrations of the oligosaccharides for inhibition of
      transcription factor binding and for transcriptional inhibition are in the
      micromolar range. The dimer is a significantly more active inhibitor than is the
      monomer.

PMID- 8570665
TI  - Sterol regulatory element binding protein binds to a cis element in the promoter
      of the farnesyl diphosphate synthase gene.
AB  - Sterol-regulated transcription of the gene for rat farnesyl diphosphate (FPP)
      synthase (geranyl-diphosphate:isopentenyl-diphosphate geranyltranstransferase, EC
      2.5.1.10) is dependent in part on the binding of the ubiquitous transcription
      factor NF-Y to a 6-bp element within the proximal promoter. Current studies
      identify a second element in this promoter that is also required for sterol
      regulated transcription in vivo. Mutation of three nucleotides (CAC) within this
      element blocks the 8-fold induction of FPP synthase promoter-reporter genes that
      normally occurs when the transfected cells are incubated in medium deprived of
      sterols. Gel mobility-shift assays demonstrate that the transcriptionally active
      68-kDa fragment of the sterol regulatory element (SRE-1)-binding protein assays
      (SREBP-1) binds to an oligonucleotide containing the wild-type sequence but not
      to an oligonucleotide in which the CAC has been mutated. DNase 1 protection
      pattern (footprint) analysis indicates that SREBP-1 binds to nucleotides that
      include the CAC. Both the in vivo and in vitro assays are affected by mutagenesis
      of nucleotides adjacent to the CAC. Coexpression of SREBP with a wild-type FPP
      synthase promoter-reporter gene in CV-1 cells results in very high levels of
      reporter activity that is sterol-independent. In contrast, the reporter activity
      remained low when the promoter contained a mutation in the CAC trinucleotide. We
      conclude that sterol-regulated transcription of FPP synthase is controlled in
      part by the interaction of SREBP with a binding site that we have termed SRE-3.
      Identification of this element may prove useful in the identification of other
      genes that are both regulated by SREBP and involved in lipid biosynthesis.

PMID- 8570667
TI  - Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous
      administration of insulin peptide B-(9-23).
AB  - The observation that overt type I diabetes is often preceded by the appearance of
      insulin autoantibodies and the reports that prophylactic administration of
      insulin to biobreeding diabetes-prone (BB-DP) rats, nonobese diabetic (NOD) mice,
      and human subjects results in protection from diabetes suggest that an immune
      response to insulin is involved in the process of beta cell destruction. We have
      recently reported that islet-infiltrating cells isolated from NOD mice are
      enriched for insulin-specific T cells, that insulin-specific T cell clones are
      capable of adoptive transfer of diabetes, and that epitopes present on residues 9
      23 of the B chain appear to be dominant in this spontaneous response. In the
      experiments described in this report, the epitope specificity of 312
      independently isolated insulin-specific T cell clones was determined and B-(9-23)
      was found to be dominant, with 93% of the clones exhibiting specificity toward
      this peptide and the remainder to an epitope on residues 7-21 of the A chain. On
      the basis of these observations, the effect of either subcutaneous or intranasal
      administration of B-(9-23) on the incidence of diabetes in NOD mice was
      determined. The results presented here indicate that both subcutaneous and
      intranasal administration of B-(9-23) resulted in a marked delay in the onset and
      a decrease in the incidence of diabetes relative to mice given the control
      peptide, tetanus toxin-(830-843). This protective effect is associated with
      reduced T-cell proliferative response to B-(9-23) in B-(9-23)-treated mice.

PMID- 8570666
TI  - B cells are not essential for peripheral T-cell tolerance.
AB  - Some self-reactive T cells avoid thymic tolerance and become mature peripheral
      cells. Nevertheless, these cells do not usually attack their hosts because T
      cells can be inactivated or killed, even after they are mature, by various means.
      The details of these processes are not fully understood; however, a number of
      experiments have suggested that peripheral tolerance may be induced in mature
      mouse T cells by exposure to antigen on resting B cells, cells that can express
      antigen bound to major histocompatibility complex proteins but that lack critical
      costimulatory molecules such as B7-1 and B7-2. Conversely, previous experiments
      have indicated that mature T cells can be stimulated by exposure to antigen on
      cells such as dendritic cells, cells that are thought to express the essential
      costimulatory molecules. We tested this idea in vivo by using mice that lack B
      cells. Unexpectedly, T-cell tolerance and antigen-induced T-cell death occurred
      normally in mice free of B cells. On the other hand, antigen-specific T-cell
      expansion in the spleens of such mice was impaired. Finally, we have recently
      shown that T-cell death in mice can be prevented by exposure to antigen and an
      inflammatory agent such as bacterial lipopolysaccharide. This was also true in
      mice that lacked B cells. Overall, these data show that mature T cells can be
      tolerized and rescued from tolerance in the absence of B cells.

PMID- 8570668
TI  - Pyrido[2,3-d]pyrimidin-4(3H)-one derivatives and 1,2,3,4-tetrahydro- pyrido[2,3
      d]pyrimidine derivatives: synthesis and in vitro study of their activity against
      platelet aggregation.
AB  - Some new derivatives of pyrido[2,3-d]pyrimidin-4(3H)-one A and 1,2,3,4-tetrahydro
      pyrido[2,3-d]pyrimidines B were prepared. The study of their in vitro
      antiaggregating activity showed that the compounds A possessed an inhibitory
      potency when aggregation was induced with ADP. Their reduction to derivatives of
      1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine B led to a new series of molecules
      possessing a greater antiaggregating power. When compared to that of
      acetylsalicylic acid under the same conditions, this activity was weaker with
      collagen, the same with arachidonic acid-induced aggregation, but greater when
      aggregation was induced by ADP. However, they inhibited serotonin release only
      slightly. Compared to ginkgolide they remained weaker with PAF-induced
      aggregation.

PMID- 8570669
TI  - Search for new anticonvulsant compounds. Part 1: Synthesis, physicochemical and
      anticonvulsant properties of new derivatives of alpha-amino-gamma
      phthalimidobutyric acid.
AB  - Synthesis and physicochemical properties of new derivatives of alpha-substituted
      gamma-phthalimidobutyric acid are described. N-substituted amides of alpha-(4
      phenylpiperazine)-gamma- phthalimidobutyric acid were prepared by condensation of
      the acid with the corresponding derivatives of benzylamine in the presence of BOP
      reagent. 2-(4-Phenylpiperazine)- or 2-(4-benzylpiperidine)-4-phthalimidobutyric
      acid were esterified with alkyl bromide in the presence of DBU or
      tetrabutylammonium bromide as catalyst. The obtained compounds were evaluated for
      anticonvulsant activity. 2-(4-Phenylpiperazine)-4-phthalimidobutyric acid and
      three N-substituted amides of this acid displaced protection against MES and
      scMet-induced seizures.

PMID- 8570670
TI  - Synthesis and biological activity of 1,2,4-triazinotriazinone derivatives.
AB  - The synthesis of 1,2,4-triazines bearing a 1,2,4-triazinone moiety and of 1,2,4
      triazolo[4,3-b]-1,2,4-triazonones have been achieved by reaction of 1,6-dihydro-3
      hydrazino-6-spiro- (9-fluorenyl)-1,2,4-triazin-5(4H)-one with various oxo- and
      halo-compounds. Structures of the products have been deduced by elemental
      analysis and spectral data. Significant anti-HIV and anticancer activities were
      observed in vitro for some members of the series.

PMID- 8570671
TI  - [The biomimetic oxidation of propiverine hydrochloride and 1-methyl-4
      piperidylbenzilate].
AB  - The reaction of propiverinhydrochloride (1) and 1-methyl-4-piperidyl benzilate
      (2) with the biomimetic system manganese(III)-5,10,15,20
      tetrakis(pentafluorophenyl)porphyrin chloride (MnTPFPPCl)/pyridine/hydrogen
      peroxide affords unchanged 1 and 2 and 15 potential metabolites, which were
      isolated and identified. These compounds are products of cleavage of the ester
      bond, of O-dealkylation, aromatic oxidation, respectively of decarboxylation,
      demethylation, and N-oxidation, Products were identified by TLC, UV, and MS in
      comparison with authentic samples. Thereby we found a nearly conformity with rat
      metabolism.

PMID- 8570672
TI  - Development of a HPLC-system for quantitative measurement of lidocaine and
      bupivacaine in patients plasma during postoperative epidural pain therapy.
AB  - A HPLC method was developed for the simultaneous quantitative analysis of
      lidocaine and bupivacaine in plasma, with bupivacaine serving as the internal
      standard for the assessment of lidocaine and vice versa. The samples are prepared
      by diethyl ether-extraction of the alkalified plasma and re-extraction using
      diluted sulphuric acid. This allows the elimination of interfering medication and
      plasma proteins. The prepared samples are chromatographed with a Merck LiChroCART
      Superspher 60 RP-select B cartridge column, the local anesthetics are detected
      using UV-photometry and the concentration is calculated by comparing the peak
      areas of the analyzed substance and the internal standard. Using a sample volume
      of 1 ml plasma, concentrations of approximately 2.5 micrograms/ml and 1
      microgram/ml can be analyzed with a 95%-confidence interval of 2.5% or 5%,
      respectively. At higher or lower concentrations, accurate results can be obtained
      using smaller or larger plasma samples. The evolved analytical method allows the
      rapid and simple determination of lidocaine and bupivacaine plasma levels at a
      wide range of concentrations. It is suitable for research purposes as well as for
      routine analyses.

PMID- 8570673
TI  - Anticonvulsant activity of aryl and hetarylsulfonylhydrazones.
AB  - A series of aryl and hetarylsulfonylhydrazones of aromatic aldehydes were tested
      for acute toxicity and anticonvulsant activity in mice. Some of these compounds
      were effective in the MES, pentetrazol and strychnine tests. Thiophene
      derivatives were the most active terms of the series.

PMID- 8570675
TI  - Influence of physical parameters on the germ-reducing effect of microwave
      irradiation on medicinal plants.
AB  - Plant material is to a different extent contaminated by microorganisms. As DAB 10
      demands limiting values for aerobic bacteria, for yeasts and moulds, a reduction
      of microorganisms of the crude herbal drug is necessary. An effective method is
      the application of microwave irradiation. The microorganisms isolated and
      identified on different herbal drugs (leaves, flowers, herbs) were mainly spore
      forming aerobic bacteria, Micrococcus luteus, and moulds of the genera
      Aspergillus and Penicillium. Various parameters such as the use of different
      microwave powers and the influence of humidity on the total count of
      microorganisms were tested according to the method described in DAB 10. It can be
      concluded from the results that microwave treatment allows careful drying with a
      germ-reducing effect, provided testing takes place under optimized and accurately
      defined conditions.

PMID- 8570674
TI  - Expression of CSA-hm2 fusion in Dictyostelium discoideum under the control of the
      Dictyostelium ras promoter reveals functional muscarinic receptors.
AB  - We have expressed the human m2 muscarinic receptor gene in the cellular slime
      mold Dictyostelium discoideum. Expression under the control of the constitutive
      actin 6 promoter without a D. discoideum leader peptide results in cells which
      seem to respond to muscarinic agonists initially, but which quickly revert to non
      responding cells only after a few generations. However, when expressing the hm2
      gene as a fusion gene together with the CSA leader peptide under the control of
      the regulated D. discoideum ras promoter cells are obtained which express
      functional muscarinic M2 receptors in a stable manner. As expected from the
      typical regulation of the ras promoter, M2 receptors are expressed only during
      development. In ligand binding assays these heterologously expressed receptors
      show binding characteristics similar to authentic M2 receptors.

PMID- 8570676
TI  - New perhydro-1,4-oxazine derivatives of arylethanolamine with beta 3-adrenoceptor
      agonist activity.

PMID- 8570677
TI  - Formulation and evaluation of terfenadine microballoons for oral controlled
      release.

PMID- 8570678
TI  - Synergistic effect of various diastereoisomeric phenylcarbamates with local
      anaesthetic activities.

PMID- 8570679
TI  - Conflict, receiver bias and the evolution of signal form.
AB  - In a model, conflicts of interest between communicating individuals are shown to
      have an important influence on the cost and form of signals that evolve. Two
      types of conflict are considered: competition between senders to obtain a
      response from the receiver, and conflict between the sender and the receiver. The
      receiver system is modelled as an artificial neural network whose 'resistance' to
      signals is represented as a motivational factor that varies independently of the
      signal. Biases in the receiver system act as the selective force on signals,
      causing them to become more costly and conspicuous as the intensity of conflict
      increases. There is some evidence that competition between senders and sender
      receiver conflict may have qualitatively different outcomes. We give examples of
      some situations to which the model might be applied and point out some
      predictions that could be tested empirically.

PMID- 8570680
TI  - Heterogeneous morphology and tracer coupling patterns of retinal
      oligodendrocytes.
AB  - The present study characterizes the morphology and tracer coupling patterns of
      oligodendrocytes in the myelinated band of the rabbit retina, as revealed by
      intracellular injection of biocytin or Lucifer yellow in an isolated superfused
      preparation. Based on the observed heterogeneity in morphology, we have grouped
      the presumptive oligodendrocytes into three categories termed 'parallel',
      'stratified' and 'radial'. Most parallel oligodendrocytes were tracer coupled to
      nearby oligodendrocytes and astrocytes, whereas the stratified and radial
      oligodendrocytes rarely showed coupling. We conclude that the different
      categories of oligodendrocytes may be stages in a developmental series, with
      radial oligodendrocytes being premyelinating cells, parallel oligodendrocytes
      being mature myelinating cells and the stratified cells representing a transition
      between these categories.

PMID- 8570681
TI  - Bovine tuberculosis in badger (Meles meles) populations in southwest England: the
      use of a spatial stochastic simulation model to understand the dynamics of the
      disease.
AB  - A spatial stochastic simulation model was developed to describe the dynamics of
      bovine tuberculosis in badger populations in southwest England, based on data
      from the literature and from unpublished sources. As there are no data on intra-
      and intergroup infection probabilities, estimates of these were obtained through
      repeated simulations based on field observations of the spread and prevalence of
      the disease. The model works on a grid-cell basis, with each grid cell
      potentially occupied by one badger social group; immigration to and emigration
      from the main grid are incorporated. Population regulation is assumed to occur at
      the group level through density-dependent fecundity and cub mortality, and the
      model can be run for various disease-free equilibrium group sizes (which are
      determined by the carrying capacity of the environment). The model works on a
      quarterly (three-monthly) basis and processes are stochastic at the individual
      level. Three classes of individual (adults, yearlings and cubs) and three classes
      of infection (susceptible, infected-but-not-infectious and infectious) are
      recognized. Bovine tuberculosis wa shown to persist in badger populations for
      long periods of time, even in populations with a disease-free equilibrium group
      size of only four adults and yearlings. However, with standard rates of
      intergroup infection and movement, the disease only became endemic in populations
      with a disease-free equilibrium group size greater than six adults and yearlings.
      In the endemic situation, the prevalence of the disease ranged between 11-22
      degrees depending on the combination of inter- and intragroup infection
      probabilities used. Endemic infection within the homogeneous environment of the
      grid was characterized by a high degree of heterogeneity. Patches of infection
      were spatio-temporally unstable, but shifted in location relatively slowly.
      Spread of the disease from a point source of infection with standard rates of
      intergroup movement and infection only occurred to any marked extent in
      populations with disease-free equilibrium group sizes of eight or more adults and
      yearlings. Increasing the intergroup infection probability had a significant
      effect on increasing the probability and rate of spread, and considerably lowered
      the threshold group size for spread from a point source to around four adults and
      yearlings. However, increasing the rates of intergroup movement reduced the
      probability of spread of the disease except at the largest groups sizes. When
      both intergroup infection and movements were increased, the effects of increased
      infection in enhancing spread were offset to some degree by the increased
      movements. Perturbation to the badger population, as may be caused by control
      operations, could therefore increase the probability of persistence or spread of
      an infection.

PMID- 8570682
TI  - Bovine tuberculosis in badger (Meles meles) populations in southwest England: an
      assessment of past, present and possible future control strategies using
      simulation modelling.
AB  - A spatial stochastic simulation model was used to compare the efficacy of
      different badger control policies and to determine the theoretical requirements
      for the control of endemic bovine tuberculosis in badger populations in southwest
      England. Culling-based strategies for controlling endemic disease were compared
      with strategies employing a yet-to-be-developed oral vaccine which would provide
      uninfected badgers with immunity to the infection. A comparative assessment was
      made of the efficacy of previous and proposed culling-based strategies employed
      by the Ministry of Agriculture, Fisheries and Food for the control of localized
      disease, and the potential for an oral vaccine-based strategy for the control of
      localized disease was examined. For endemic bovine tuberculosis, to achieve a
      reasonable probability (p > 0.70) of successful control with a strategy involving
      a single culling operation, a very high proportion of the badger population (>
      90%) must be culled. Single vaccination would not be successful in combating
      endemic disease. However, strategies involving repeated annual vaccination would
      have a very high probability of eradicating endemic disease, even with a
      relatively low (40-50%) annual vaccination efficiency. The most successful
      culling-based strategies for the control of localized disease were the gassing
      and clean ring strategies. Compared with no control at all, the interim strategy
      only offered benefits of a lower probability of disease spread and persistence in
      populations with low disease-free equilibrium group sizes or low initial
      prevalences of infection. In all other instances the benefits were negligible.
      The live test strategy will offer an improvement over the interim strategy, but
      will not be as effective as either the gassing or clean-ring strategies. In
      addition, it is likely to necessitate the culling of approximately four times as
      many badgers each year as the interim strategy, and the proportion of those
      killed that are infected will be approximately half that under the interim
      strategy. The efficacy of a strategy involving annually repeated oral vaccination
      of the badgers within a similar area to that covered by the live test depended on
      the efficiency of vaccination. A vaccination efficiency of 20-60% represented an
      overall improvement in efficacy over the interim strategy, being equivalent to
      the live test strategy. However, only vaccination efficiencies of 60-80% or
      greater achieved similar results to the gassing strategy, and none were so
      successful as the clean-ring strategy. Recommendations for future management are
      provided. Reactive strategies based on culling or vaccination will not solve the
      problem of bovine tuberculosis in badgers. Proactive strategies directed in those
      areas with a recent history of bovine tuberculosis in badgers should be
      considered as an alternative short-term control measure. The only strategy likely
      to eradicate bovine tuberculosis from badger populations in the long term is the
      use of repeated vaccination in proactive control operations in areas with a
      history of bovine tuberculosis in the badger population. Analyses should be
      conducted to evaluate whether the economic benefits of the live-test strategy are
      likely to outweigh its economic and ecological costs and whether continued
      research into the development of a vaccine for badgers is likely to offer any
      significant long-term economic benefits.

PMID- 8570683
TI  - The molecular genetics of Sry and its role in mammalian sex determination.
AB  - The process of sex determination, by which is meant the decision as to whether an
      embryo develops as a male or a female, is considered as a paradigm of how gene
      action can influence developmental fate. In mammals the decision is dependent on
      the action of the testis determining gene present on the Y chromosome, now known
      to be the gene Sry. Sry is expressed for only a brief period in the mouse embryo
      and must act to initiate rather than maintain the pathway of gene activity
      required for testis differentiation. It probably acts within cells of the
      supporting cell lineage to direct their differentiation into Sertoli cells,
      rather than the granulosa cells characteristic of the ovary. Other lineages in
      the gonad then follow the male pathway. The nature of the Sry transcript in the
      genital ridge of mice has been determined and compared with that from the human
      gene which is dramatically different. The expression of Sry has been carefully
      examined during the critical stages of genital ridge development and compared to
      the expression of a number of other genes involved in gonadal development and
      male development such as that for anti-Mullerian hormone. This has defined the
      period in which Sry must act to between 11 and 11.5 days post coitum. The
      expression of Sry has also been examined in cases of sex reversal in the mouse.
      There is a dependence on level of expression and extent of testicular
      differentiation that suggests thresholds for both the amount of SRY per cell and
      the number of cells expressing the gene. The SRY protein interacts with DNA
      through an HMG box type of DNA binding domain, however at present no definite
      target genes have been found. Progress on strategies to find such genes is
      discussed.

PMID- 8570684
TI  - Interaction of normal and mutant SRY proteins with DNA.
AB  - In mammals, sex determination is caused by the Y-chromosome gene SRY. The DNA
      binding domain of human SRY protein is similar to those of the chromatin protein
      HMG1. Like HMG1, SRY binds to kinked DNA structures, and bends linear DNA sharply
      upon binding. We analysed the biochemical properties of mutant SRY proteins from
      five patients with complete gonadal dysgenesis: two bind and bend DNA almost
      normally, two bind inefficiently but bend DNA normally, and one binds DNA with
      almost normal affinity but produces a different angle. The mutations with
      moderate effect on complex formation can be transmitted to progeny, the ones with
      severe effects on either binding or bending are de novo. The angle induced by SRY
      depends on the exact DNA sequence, thus discriminating different target sites. We
      suggest that the exact spatial arrangement of the nucleoprotein complex organized
      by SRY in chromatin is essential for the expression of genes involved in testis
      differentiation.

PMID- 8570685
TI  - The nature of gene evolution on the mammalian Y chromosome: lessons from Sry.
AB  - With the exception of a small region, heteromorphic sex chromosomes of mammals do
      not undergo recombination in male meiosis. As a result, the majority of the Y
      chromosome is clonally transmitted through paternal lineages. Numerous phenomena,
      including the Hill-Robertson effect, Muller's ratchet, genetic hitch-hiking, and
      male-driven molecular evolution, are associated with the special transmission
      properties of the Y chromosome, and can potentially explain the tempo and pattern
      of gene evolution on the mammalian Y. We explore these phenomena in light of
      comparative data from the Y-linked sex-determining locus, Sry. Sry exhibits rapid
      amino acid divergence between species and little to no variation within species.
      We find no evidence for directional selection acting on this locus. The pattern
      of evolution between species is consistent with the Hill-Robertson effect and
      Muller's ratchet. Lack of variation in Sry within species may reflect genetic
      hitch-hiking, however, we cannot exclude the confounding effects of small
      effective population size of Y chromosomes. We find no support for male-driven
      molecular evolution for Sry in Old World mice and rats. However, a more
      appropriate test of this hypothesis would be to compare the evolution of Sry to
      the X-linked Sox3 gene in these same species. Clearly, more comparative studies
      of Sry and other Y-linked loci are needed to characterize the effects of Y
      chromosome transmission on the evolution of Y-linked sequences.

PMID- 8570686
TI  - Germ cells and germ cell sex.
AB  - Whether germ cells succeed in making eggs or sperm depends both on their genetic
      constitution and on the tissue environment in which they develop. The decision as
      to whether it is oogenesis or spermatogenesis on which they initially embark
      depends only on their environment, however, and not at all on their own
      chromosomes. The foetal testis of the mouse produces an inhibitor of meiosis:
      germ cells that are exposed to it develop as prospermatogonia. Germ cells in the
      foetal ovary enter meiosis and develop as oocytes: this may represent the default
      pathway for germ cell sexual differentiation, or there may exist a meiosis
      inducing substance. Experimental evidence suggests that any such substance must
      be present ubiquitously, not just in the ovary. The stage of foetal development
      at which meiosis is initiated may be programmed in the germ cell lineage.

PMID- 8570687
TI  - Three-dimensional structure of the developing mouse genital ridge.
AB  - We are interested in understanding how the field of cells which forms the gonad
      arises, and how the testis-determining gene, Sry, controls morphogenesis of a
      testis within this field of cells. To appreciate changes in the three-dimensional
      structure of the mouse genital ridge at this time in development, whole-mount
      genital ridges taken from male and female embryos over the developmental period
      when the initiation of testis cord morphogenesis takes place, were stained with
      an antibody against laminin. Samples were visualized using confocal microscopy.
      Anti-laminin illuminates the elaborate array of mesonephric duct and tubules
      which occupy the cranial two-thirds of the mesonephros at the earliest timepoint.
      This complex structure gradually regresses as testis cords form in male gonads.
      No structural organisation is recognized by this antibody in the female gonadal
      region during this period. Confocal sections in the Z-plane reveal continuous
      cellular connections between 3-6 mesonephric tubules and the gonadal primordium.
      These cellular bridges are present in male and female gonads, so they do not
      depend on the expression of Sry. We consider the possibility that these bridges
      constitute the pathways of the founder cells of the gonadal primordium.

PMID- 8570688
TI  - The marsupial male: a role model for sexual development.
AB  - Sexual differentiation in male marsupials has many similarities with that of
      eutherians. Marsupials have an XX-XY sex determining mechanism, and have a
      homologue of the testis-determining SRY gene on their Y-chromosome. However, the
      development pattern of SRY gene expression is different from the mouse in that it
      is expressed for a much longer period. SRY is expressed in a range of non-gonadal
      tissues in male pouch young and adults which is similar to the human pattern, and
      raises questions as to its particular role(s) in sexual differentiation.
      Similarly Mullerian inhibiting substance (MIS) is produced in the developing
      testis over a longer period than in the mouse. Since ovaries cultured with MIS or
      transplanted into male recipient pouch young develop tubular structures, MIS may
      induce Sertoli cell formation. Testosterone is produced by the neonatal testis,
      and this stimulates Wolffian duct development to form the vas deferens and
      epididymis. Virilization of urogenital sinus is also androgen-dependent. However,
      virilization of the prostate and phallus occurs more than three weeks after the
      onset of testosterone production, suggesting that the timing of this may be
      regulated by delayed activation of the androgen receptor pathway. Unlike in
      eutherians, differentiation of the scrotum and mammary glands is not dependent on
      testicular hormones, but is independently regulated by an X-linked genetic
      mechanism. Clearly marsupials provide a unique perspective to help us clarify the
      mechanisms underlying sexual development in all mammals.

PMID- 8570689
TI  - The genetic basis of XX-XY differences present before gonadal sex differentiation
      in the mouse.
AB  - There is now a substantial body of data showing that in eutherian mammals (mouse,
      rat, cow and man) XY conceptuses are developmentally more advanced (and
      consequently larger) than XX conceptuses of equivalent gestational age. This
      developmental difference is already discernible in the preimplantation period and
      it has been suggested that the more advanced development of XY embryos may be a
      consequence of the preimplantation expression of Y chromosomal genes such as Sry
      or Zfy. In the present paper sex-chromosomally variant mice were used to analyse
      the genetic basis of XX-XY differences as manifest at 10.5 days post coitum. The
      results show that the XX-XY difference is due to a combination of a Y chromosome
      effect and an effect of the difference in X chromosome constitution (2X v 1X).
      The Y effect is not dependent on the presence of Sry. In the light of this and
      other studies, it is concluded that the Y chromosome of most mouse strains
      carries a factor which accelerates preimplantation development and that the
      resulting developmental advantage is carried over into the postimplantation
      period. The retarding effect of two X chromosomes is then superimposed on this Y
      effect subsequent to the blastocyst stage but prior to 9.5 days post coitum.

PMID- 8570690
TI  - Sex reversal in C57BL/6J-YPOS mice corrected by a Sry transgene.
AB  - C57BL/6J mice carrying a Mus domesticus poschiavinus Y chromosome (YPOS) develop
      as females with ovarian tissue or as hermaphrodites with ovarian and testicular
      tissue. We tested the hypothesis that the Y-linked component of this inherited
      sex reversal is caused by the M. d. poschiavinus Y-linked testis determining gene
      (symbolized Tdy or Sry) by examining gonadal development in C57BL/6J XYPOS mice
      carrying a M. musculus allele of Sry as a transgene. We found that in the
      presence of the transgene, XYPOS mice developed exclusively testicular tissue.
      This result indicates that the Sry allele carried on the YPOS chromosome is
      responsible for development of ovarian tissue in the C57BL/6J inbred strain
      background. We discuss this finding in light of DNA polymorphisms present in Sry
      alleles carried by various M. domesticus and M. musculus Y chromosomes. In
      addition, we present a hypothesis concerning the timing of expression of the
      testicular and ovarian determining genes in the developing fetal gonad based on
      the organization of ovarian and testicular tissue in ovotestes.

PMID- 8570691
TI  - The role of SOX9 in autosomal sex reversal and campomelic dysplasia.
AB  - In eutherian mammals, the Y-chromosome gene SRY is required for induction of
      testis development. Although the Y chromosome is sex determining, loci located
      elsewhere in the genome participate in the complex cascade of genetic
      interactions required to form a testis. Male to female sex reversal (46,XY
      females) occurs at a high frequency in individuals afflicted with the skeletal
      malformation syndrome campomelic dysplasia. Chromosomal translocations in
      individuals with both syndromes had localized an autosomal sex reversal locus
      (SRA1) and a campomelic dysplasia locus (CMPD1) to the long arm of human
      chromosome 17. The molecular cloning of a translocation breakpoint in a sex
      reversed campomelic dysplasia patient revealed its proximity to SOX9, a gene
      which is related to SRY. Analysis of SO X9 in patients without chromosomal
      rearrangements demonstrated single allele mutations in sex reversed campomelic
      individuals, linking this gene with both bone formation and control of testis
      development. Identification of SO X9 as SRA1/CMPD1 and the role of SO X9
      mutations in sex reversal and campomelic dysplasia are discussed.

PMID- 8570692
TI  - The cell-specific nuclear receptor steroidogenic factor 1 plays multiple roles in
      reproductive function.
AB  - The cytochrome P450 steroid hydroxylases exhibit tissue-specific and
      developmentally regulated gene expression. Recent studies showed that the orphan
      nuclear receptor steroidogenic factor 1 (SF-1) plays a key role in their gene
      regulation. In mouse embryos, SF-1 expression began at the inception of adrenal
      and gonadal development, suggesting that SF-1 plays a key role in the
      steroidogenic cell differentiation. SF-1 was also expressed in the developing
      pituitary gland and diencephalon, which raised the possibility that it also has
      additional roles in endocrine development. To examine the role of SF-1 in intact
      mice, we disrupted the gene encoding SF-1 by homologous recombination in
      embryonic stem cells; this approach ultimately permitted us to generate SF-1
      knockout mice in which the gene encoding SF-1 was inactivated. These studies
      revealed essential roles of SF-1 in endocrine development that included adrenal
      and gonadal development, expression of several markers of pituitary gonadotropes,
      and formation of the ventromedial hypothalamic (VMH) nucleus. These results
      indicate that SF-1 acts at multiple levels of the reproductive axis to maintain
      reproductive competence.

PMID- 8570693
TI  - The mullerian inhibitor and mammalian sexual development.
AB  - The elegant embryological experiments of Jost demonstrated the existence of a
      foetal testicular factor that is required to cause the regression of the
      mullerian duct system, the anlagen of the uterus, oviducts and upper portion of
      the vagina, during male sexual development. The mullerian inhibitor currently
      known as mullerian-inhibiting substance (MIS) or anti-mullerian hormone (AMH), is
      a member of the transforming growth factor-beta (TGF-beta) family of growth and
      differentiation factors. The genetic manipulation of the mouse germline has lead
      to the generation of animal models for MIS function. Female transgenic mice that
      chronically express MIS during embryogenesis are born without a uterus or
      oviducts and their ovaries lose germ cells and degenerate, recapitulating the
      phenotype of the bovine freemartin. Some male transgenic mice from very high MIS
      expressing lines are feminized, suggesting alterations in androgen biosynthesis.
      Male mice homozygous for a targeted mutation of the MIS gene develop as male
      pseudohermaphrodites with both male (testes and Wolffian duct-derived) and female
      (mullerian duct-derived) reproductive organs. Most are infertile because the
      development of two reproductive systems physically blocks the exit of sperm from
      these males. In addition, Leydig cell hyperplasia is detected in a proportion of
      these males and in one case a Leydig cell tumour was found. Recently, a gene
      encoding a TGF-beta family type II Ser/Thr kinase membrane-bound receptor has
      been isolated that is expressed in both male and female gonads and in the
      mesenchyme surrounding the mullerian ducts during embryogenesis. These findings
      suggest that MIS-mediated mullerian duct regression occurs indirectly through
      mesenchymal tissue. A targeted mutation of this receptor has been established in
      the mouse germline. Mice homozygous for this receptor mutation should be useful
      in understanding the MIS signalling pathway for mullerian duct regression and
      gonadal function.

PMID- 8570694
TI  - Xp duplications and sex reversal.
AB  - Male to female sex reversal has been observed in individuals with duplications of
      the short arm of the X chromosome. The study of Xp duplicated patients
      demonstrated that sex reversal results from the presence of two active copies of
      the DSS (dosage sensitive sex reversal) locus. A double dosage of DSS disrupts
      testis formation whereas its absence is compatible with a male phenotype,
      suggesting a role for DSS in ovarian development and as a link between ovary and
      testis formation. DSS was localized to a 160 kb region of Xp21, overlapping the
      adrenal hypoplasia congenita locus. The search for expressed sequences in the DSS
      critical region led to the identification of two types of genes: the DAM family
      and DAX-1, an atypical member of the nuclear receptor superfamily. Although no
      function is currently known for DAM genes, functional deficiency for DAX-1 has
      been shown to be responsible for adrenal hypoplasia congenita and
      hypogonadotropic hypogonadism. The search for the DSS gene(s) is still open and
      both the DAM genes and DAX-1 represent DSS candidate genes.

PMID- 8570695
TI  - The molecular biology of temperature-dependent sex determination.
AB  - Many reptiles do not have heteromorphic sex chromosomes and for these species sex
      is determined during embryogenesis by the temperature of egg incubation rather
      than at conception. The phenomenon of temperature-dependent sex determination
      (TSD) was discovered almost thirty years ago, but few advances have been made
      towards the elucidation of its mechanism. In the past few years substantial
      progress has been made in the understanding of the molecular basis of XY
      chromosomal (genetic) sex determination (GSD) through the discovery of SRY. It is
      now possible to start comparing TSD with GSD. TSD is found in some evolutionarily
      ancient vertebrates and has been postulated to be the ancestral process from
      which GSD has evolved. If this is true then the two mechanisms may share a common
      molecular basis. This paper details the current knowledge of TSD, our progress on
      the investigation of the involvement of SRY-type proteins, and finally presents
      some of the problems that need to be resolved to gain an understanding of the
      molecular basis of TSD.

PMID- 8570696
TI  - The evolution of mammalian sex chromosomes and the origin of sex determining
      genes.
AB  - Mammals have XX female: XY male chromosomal sex determination in which a small
      heterochromatic Y controls male development. Only a few active genes have been
      identified on the Y, including the testis determining factor SRY and candidate
      spermatogenesis genes. These genes, as well as several pseudogenes, have close
      relatives on the X, confirming that the Y was originally homologous to the X, but
      has been progressively degraded. We used comparative gene mapping of sex
      chromosomes from the three major groups of extant mammals (eutherians, marsupials
      and monotremes) to deduce how the X and Y evolved from a pair of autosomes, and
      how SRY assumed control of sex determination. We found that part of the X, and a
      corresponding region of the Y chromosome, is shared by all mammals and must be
      very ancient, but part of the X (and Y) was added quite recently. I propose that
      a small original X and Y were enlarged by cycles of autosomal addition to one
      partner, recombination onto the other and continuing attrition of the compound Y.
      This addition-attrition hypothesis predicts that the pseudoautosomal region of
      the human X is merely a relic of the last addition, and that the gene content of
      the pseudoautosomal region may well differ in different mammalian lineages. The
      only genes which remained active on the conserved or added regions of the Y were
      those, like SRY, that evolved functions in male sex determination and
      differentiation distinct from the general functions of their X-linked partners.
      Although the vertebrate gonadogenesis pathway is highly conserved, its control
      circuitry has probably changed radically and rapidly in evolution.

PMID- 8570697
TI  - Advances in photochemical approaches for blood sterilization.

PMID- 8570698
TI  - The role of epidermal cytokines in the generation of cutaneous immune reactions
      and ultraviolet radiation-induced immune suppression.

PMID- 8570699
TI  - Photochemistry of type I acid-soluble calf skin collagen: dependence on
      excitation wavelength.
AB  - Although previous studies have demonstrated that the predominant photochemistry
      of type I collagen under 254 nm irradiation may be attributed either to direct
      absorption by tyrosine/phenylalanine or to peptide bonds, direct collagen
      photochemistry via solar UV wavelengths is much more likely to involve several
      age- and tissue-related photolabile collagen fluorophores that absorb in the
      latter region. In this study, we compare and contrast results obtained from
      irradiation of a commercial preparation of acid-soluble calf skin type I collagen
      in solution with UVC (primarily 254 nm), UVA (335-400 nm) and broad-band solar
      simulating radiation (SSR; 290-400 nm). Excitation spectroscopy and analysis of
      photochemically induced disappearance of fluorescence (fluorescence fading)
      indicates that this preparation has at least four photolabile fluorescent
      chromophores. In addition to tyrosine and L-3,4-dihydroxyphenylalanine, our
      sample contains two other fluorophores. Chromophore I, with emission maximum at
      360 nm, appears to be derived from interacting aromatic moieties in close mutual
      proximity. Chromophore II, with broad emission at 430-435 nm, may be composed of
      one or more age-related molecules. Collagen fluorescence fading kinetics are
      sensitive to excitation wavelength and to conformation. Under UVC, chromophore I
      fluorescence disappears with second-order kinetics, indicating a reaction between
      two proximal like molecules. Adherence to second-order kinetics is abrogated by
      prior denaturation of the collagen sample. A new broad, weak fluorescence band at
      400-420 nm, attributable to dityrosine, forms under UVC, but not under solar
      radiation. This band is photolabile to UVA and UVB wavelengths.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8570700
TI  - A comparative study of the visible light photochemistry of gilvocarcins V and M.
AB  - Quantum yields for the formation of superoxide ions, O2-., and singlet oxygen,
      1O2, were determined during the photolyses of gilvocarcin M (GM) in air-saturated
      dry dimethylsulfoxide (DMSO) and in 45:55 (vol/vol) DMSO-water mixtures. The
      quantum yield for the photoreduction of methyl viologen by GM in nitrogen
      saturated dry DMSO was also determined. These values are not different, within
      experimental error, from those corresponding to gilvocarcin V (GV). Because GV is
      a strong photocytotoxic agent and GM is not, these results imply that Type I and
      Type II mechanisms are not important pathways in the cytotoxicity of GV.

PMID- 8570701
TI  - The use of exogenous fluorescent probes for temperature measurements in single
      living cells.
AB  - The fluorescent membrane probes 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) and 6
      dodecanoyl-2-dimethylamino-naphthalene (laurdan) have been studied for use as
      optical thermometers in living cells. The thermal sensitivity of NBD is primarily
      a consequence of rapid, heat-induced electronic changes, which increase the
      observed fluorescence decay rate. As a result, fluorescence intensity and
      lifetime variations of membrane-bound NBD-conjugated phospholipids and fatty
      acids can be directly correlated with cellular temperature. In contrast, laurdan
      fluorescence undergoes a dramatic temperature-dependent Stokes shift as the
      membrane undergoes a gel-to-liquid-crystalline phase transition. This facilitates
      the use of fluorescence spectra to record the indirect effect of
      microenvironmental changes, which occur during bilayer heating. Microscope and
      suspension measurements of cells and phospholipid vesicles are compared for both
      probes using steady-state and fluorescence lifetime (suspension only) data. Our
      results show that NBD fluorescence lifetime recordings can provide reasonable
      temperature resolution (approximately 2 degrees C) over a broad temperature
      range. Laurdan's microenvironmental sensitivity permits better temperature
      resolution (0.1-1 degree C) at the expense of a more limited dynamic range that
      is determined solely by bilayer properties. The temperature sensitivity of NBD is
      based on rapid intramolecular rotations and vibrations, while laurdan relies on a
      slower, multistep mechanism involving bilayer rearrangement, water penetration
      and intermolecular processes. Because of these differences in time scale, NBD
      appears to be more suitable for monitoring ultrafast phenomena, such as the
      impact of short-pulse microirradiation on single cells.

PMID- 8570702
TI  - Chemiluminescence and EPR studies on the excitation site of ferric-heme-oxo
      complexes of natural and model heme systems.
AB  - Chemiluminescence was detected both in the reaction system of H2O2 plus heme
      proteins such as methemo- and metmyoglobin and ferric-protoheme complexes used as
      a model system. The intensity of chemiluminescence was found to be mediated by
      ligand binding to the sixth coordination site of the ferric-protoheme compounds,
      e.g. chemiluminescence was not observed with the bisimidazole ferric-protoheme
      complex. On the other hand the pentacoordinated histidine ferric-protoheme
      complex exhibited strong light emission. Comparative studies with various ligand
      heme compounds elucidated that light emission was inversely correlated with the
      binding strength of the respective ligand at the sixth coordination site. The
      basic reaction mechanism causing the establishment of an excited state was
      studied by monitoring chemiluminescence and EPR signal formation of ligand
      modified heme proteins in the presence of different electron donors. External
      electron donors such as Trolox C, TMPD and ascorbic acid affected a strong
      reduction in the development of chemiluminescence suggesting the essential
      involvement of an inner-molecular electron transfer process. Our results allow
      the conclusion that chemiluminescence is generated from the decay of an excited
      state of oxo-heme compounds established as a result of a one electron transfer
      step from a ligand group to heme iron.

PMID- 8570703
TI  - Regulation and inhibition of collagenase expression by long-wavelength
      ultraviolet radiation in cultured human skin fibroblasts.
AB  - The cellular mechanisms responsible for the connective tissue changes produced by
      chronic exposure to UV light are poorly understood. Collagenase, a
      metalloproteinase, initiates degradation of types I and III collagen and thus
      plays a key role in the remodeling of dermal collagen. Collagenase synthesis by
      fibroblasts and keratinocytes involves the protein kinase C (PKC) second
      messenger system, and corticosteroids have been shown to suppress its synthesis
      at the level of gene transcription. Long-wavelength UV light (UVA, 320-400 nm)
      stimulates the synthesis of interstitial collagenase, as well as increasing PKC
      activity, in human skin fibroblasts in vitro. This study explores the regulation
      of collagenase expression by UVA in cultured human skin fibroblasts.
      Specifically, the time course, the effect of actinomycin D, an inhibitor of RNA
      synthesis, as well as the effect of PKC inhibitors and dexamethasone on
      expression of collagenase following UVA irradiation were examined. After UVA
      irradiation, collagenase mRNA rose rapidly between 4 and 12 h postirradiation,
      peaking 18 h post-UVA. Actinomycin D completely suppressed the UVA-induced
      increase in collagenase mRNA. Thus, new RNA synthesis is required for the UVA
      induced increase in collagenase mRNA. The PKC inhibitor, H-7, blocked the
      increase in collagenase mRNA in response to UVA in a dose-dependent manner.
      Similarly, dexamethasone also inhibited collagenase gene expression induced by
      UVA in a dose-dependent fashion; the majority of the inhibitory effect was seen
      within the first 4 h after irradiation. These studies demonstrate that the effect
      of UVA on collagenase gene expression is regulated at the pretranscriptional
      level and may involve the PKC pathway.

PMID- 8570704
TI  - The action spectra for UV-induced suppression of MLR and MECLR show that
      immunosuppression is mediated by DNA damage.
AB  - Ultraviolet-B (UVB, 280-320 nm) radiation can promote the induction of skin
      cancer by two mechanisms: damage of epidermal DNA and suppression of the immune
      system, allowing the developing tumor to escape immune surveillance. The mixed
      lymphocyte reaction (MLR) and the mixed epidermal cell lymphocyte reaction
      (MECLR) are commonly used methods to study the immunosuppressive effects of UVB
      radiation. To obtain a better understanding of the mechanism by which UVB
      radiation decreases the alloactivating capacity of in vitro-irradiated cells,
      action spectra for the MLR and MECLR were determined. Suspensions of peripheral
      blood mononuclear cells or epidermal cells were irradiated with monochromatic
      light of 254, 297, 302 or 312 nm and used as stimulator cells in the MLR or
      MECLR. Using dose-response curves for each wavelength, the action spectra were
      calculated. Both MLR and MECLR action spectra had a maximum at 254 nm and a
      relative sensitivity at 312 nm that was a thousand times lower than at 254 nm.
      Strikingly, the action spectra corresponded very closely to the action spectra
      that were found by Matsunaga et al. (Photochem. Photobiol. 54, 403-410, 1991) for
      the induction of thymine dimers and (6-4)photoproducts in irradiated calf thymus
      DNA solutions, strongly suggesting that the UV-induced abrogation of the MLR and
      MECLR responses is mediated by UV-induced DNA damage. Furthermore, the action
      spectra for the MLR and MECLR were similar, suggesting that they share a common
      mechanism for UV-induced suppression.

PMID- 8570705
TI  - Ascorbic acid glycation of lens proteins produces UVA sensitizers similar to
      those in human lens.
AB  - Soluble calf lens proteins were extensively glycated during a 4 week incubation
      with ascorbic acid in the presence of oxygen. Amino acid analysis of the dialyzed
      proteins removed at weekly intervals showed an increasing loss of lysine,
      arginine and histidine, consistent with the extensive protein cross-linking
      observed. Irradiation of the dialyzed samples with UVA light (1.0 kJ/cm2 total
      illumination through a 338 nm cutoff filter) caused an increasing loss of
      tryptophan, an additional loss of histidine and the production of micromolar
      concentrations of hydrogen peroxide. No alteration in amino acid content and no
      photolytic effects were seen in proteins incubated without ascorbic acid or in
      proteins incubated with glucose for 4 weeks. The rate of hydrogen peroxide
      formation was linear with each glycated sample with a maximum production of 25
      nmol/mg protein illuminated. The possibility that the sensitizer activity was due
      to an ascorbate-induced oxidation of tryptophan was eliminated by the presence of
      a heavy metal ion chelator during the incubation and by showing equivalent
      effects with ascorbate-incubated ribonuclease A, which is devoid of tryptophan.
      The ascorbate-incubated samples displayed increasing absorbance at wavelengths
      above 300 nm and increasing fluorescence (340/430) as glycation proceeded. The
      spectra of the 4 week glycated proteins were identical to those obtained with a
      solubilized water-insoluble fraction from human lens, which is known to have UVA
      sensitizer activity. The incubation of lens proteins with dehydroascorbic acid or
      L-threose, but not fructose, produced equivalent glycation, protein crosslinking
      and sensitizer activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570706
TI  - Activation of NF-kappa B in human skin fibroblasts by the oxidative stress
      generated by UVA radiation.
AB  - We have examined the role of the nucleus and the membrane in the activation of
      nuclear factor (NF)-kappa B by oxidant stress generated via the UVA (320-380 nm)
      component of solar radiation. Nuclear extracts from human skin fibroblasts that
      had been irradiated with UVA at doses that caused little DNA damage contained
      activated NF-kappa B that bound to its recognition sequence in DNA. The UVA
      radiation-dependent activation of NF-kappa B in enucleated cells confirmed that
      the nucleus was not involved. On the other hand, UVA radiation-dependent
      activation of NF-kappa B appeared to be correlated with membrane damage, and
      activation could be prevented by alpha-tocopherol and butylated hydroxytoluene,
      agents that inhibited UVA radiation-dependent peroxidation of cell membrane
      lipids. The activation of NF-kappa B by the DNA damaging agents UVC (200-290 nm)
      and UVB (290-320 nm) radiation also only occurred at doses where significant
      membrane damage was induced, and, overall, activation was not correlated with the
      relative levels of DNA damage induced by UVC/UVB and UVA radiations. We conclude
      that the oxidative modification of membrane components may be an important factor
      to consider in the UV radiation-dependent activation of NF-kappa B over all
      wavelength ranges examined.

PMID- 8570707
TI  - UVB-induced suppression of the mixed epidermal cell lymphocyte reaction is
      critically dependent on irradiance.
AB  - The mixed epidermal cell lymphocyte reaction (MECLR) is a commonly used method to
      study the effects of ultraviolet B (UVB) radiation on the skin immune system. In
      UVB experiments dosimetry is very important. The influence of irradiance on the
      MECLR was studied in vitro using Philips FS40 lamps with variable UV intensities.
      Irradiation of isolated epidermal cells with high irradiance impaired the
      alloactivating capacity more than irradiation with low irradiance. In vivo, the
      influence of long-term UVB exposure on the MECLR was studied by treating normal
      healthy volunteers with suberythemagenic doses of UVB thrice weekly during 4
      weeks. The first set of experiments, using low irradiance Sylvania UV-21 F75/85 W
      lamps, resulted in a decrease of MECLR responses of 83.1%. In the second set of
      experiments performed a year later, employing an identical protocol except for
      the use of high irradiance Waldmann UV-21 F85/100 W lamps, an increase of MECLR
      responses of 99.7% was observed. Volunteers of both sets of experiments received
      equal doses of UVB. In conclusion, this study shows that in vitro UVB-induced
      suppression of the MECLR is critically dependent on irradiance and therefore
      might explain contradictory results described in the literature. The in vivo data
      suggest that, comparable to the in vitro experiments, irradiance may influence
      the effects of UVB irradiation in vivo. Further experiments should prove whether
      this is indeed the case.

PMID- 8570708
TI  - Stimulatory and inhibitory effects of iron on photodynamic inactivation of
      leukemia cells.
AB  - The influence of exogenous iron on merocyanine 540 (MC540)-sensitized
      photoinactivation of leukemia cells has been investigated. Irradiation of murine
      L1210 or human HL-60 cells (approximately 10(6)/mL in 1% serum/RPMI medium) with
      broadband visible light in the presence of MC540 (2 microM) resulted in a
      progressive loss of clonally assessed cell viability. When added to cells 30 min
      before irradiation, the low polarity chelate, ferric 8-hydroxyquinoline [Fe(HQ)2,
      0.5 microM] stimulated dye-sensitized photokilling, whereas high polarity
      chelates such as ferric 8-hydroxyquinoline-5-sulfonate [Fe(HQS)2, 0.5 microM] or
      ferric ethylenediaminetetraacetate (Fe.EDTA, 0.5 microM) had no no effect. A
      striking reversal of Fe(HQ)2-enhanced photokilling was observed upon increasing
      the preirradiation incubation time with Fe(HQ)2 such that a marked resistance
      (relative to non-iron-treated controls) was evident after 24 h. Cells exposed for
      24 h to Fe(HQS)2 or Fe.EDTA showed similar or even greater resistance to
      photokilling. Like phototoxicity, H2O2-induced cytotoxicity was enhanced after a
      30 min exposure of cells to Fe(HQ)2 but strongly repressed after 24 h. Immunoblot
      (western) analysis, using a polyclonal antibody to ferritin, revealed that cells
      exposed to Fe(HQ)2 for 24 h contained at least 12 times as much ferritin heavy
      chain as non-Fe(HQ)2-treated controls. Preincubating cells with emetine, an
      inhibitor of protein synthesis, prevented both ferritin induction and the
      development of hyperresistance. These findings, along with the observation that
      exogenous apoferritin protected L1210 cells against photokilling, suggest a
      possible role for ferritin in iron-stimulated photoresistance.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8570709
TI  - Octa-alkyl zinc phthalocyanines: potential photosensitizers for use in the
      photodynamic therapy of cancer.
AB  - The synthesis, characterization and electronic spectra of a series of nine
      1,4,8,11,15,18,22,25-octa-alkyl zinc phthalocyanines (ZnPc), potential
      photosensitizers for the photodynamic therapy of cancer, are described. The
      substituents on the phthalocyanine (Pc) macrocycle "red-shift" the absorbance
      maximum, in cyclohexane, of all nine members of this series to a value of 703 +/-
      2 nm, with a corrected fluorescence emission maximum for the octadecyl derivative
      of 715 nm. The solubilities and degree of aggregation of six examples in
      cyclohexane have been measured. The highest homologue, the octadecyl derivative,
      remains essentially unaggregated to a concentration of 1.5 x 10(-4) mol dm-3. the
      photostability of this Pc has been examined and the compound shown to be
      sensitive to photooxidation processes which lead to its decomposition to 3,6-bis
      decylphthalimide. Known singlet oxygen quenchers inhibit the photodecomposition.
      In a comparative study, the octadecyl ZnPc underwent a more rapid
      photodecomposition than the corresponding metal-free derivative.

PMID- 8570710
TI  - Subcellular distribution of hypericin in human cancer cells.
AB  - Confocal laser microspectrofluorometric measurements on human T47D mammary tumor
      cells have been performed to assess the intracellular distribution of hypericin
      within the various cell compartments: cytoplasmic membrane, cytoplasm and
      nucleus. Confocal fluorescence measurements obtained from microvolumes
      (approximately 1 micron3) located within the three sites of interest show that,
      while being primarily located in the cell membrane and cytoplasm after a short
      term incubation in a 10(-6) M hypericin-containing culture medium, hypericin
      actually reaches the inside of the cell nucleus after a long-term incubation (210
      min). Moreover, owing to the relative fluorescence quantum yields of hypericin
      determined in vitro when the molecule interacts with DNA, membrane and protein
      model systems, it is assumed that there is a significant accumulation of the drug
      into the cell nucleus. Consequently, the nucleus has to be considered as a
      possible target for the toxic action of hypericin.

PMID- 8570711
TI  - Characteristics of the chemiluminescence from the blood plasma of a normal human
      population.
AB  - Oxygen-dependent chemiluminescence was detected from human blood plasma. The
      intensity of the chemiluminescence increased about three-fold under oxygenation
      and decreased almost to the background (zero) level under a nitrogen atmosphere.
      The blood plasma from a sample (n = 100) of donors was tested to determine the
      variability of several properties of the chemiluminescence in a normal
      population. No statistically significant difference in blood plasma
      chemiluminescence between genders was found, but there was a slight increase in
      luminescence intensity with age. However, the results were found to be dependent
      on a number of other factors, such as diet, smoking and the length of time
      between the donor's last meal and the sampling of the blood. Some of the trends
      in the results coincide with similar trends in the plasma lipoprotein levels and
      thus support the suggestion that the chemiluminescence arises from the
      decomposition of lipid hydroperoxides. These factors must all, therefore, be
      taken into account when using chemiluminescence as an indicator of illness.

PMID- 8570712
TI  - EPR persistence measurements of UV-induced melanin free radicals in whole skin.
AB  - Electron paramagnetic resonance is used to detect the formation of free radicals
      caused by exposure to ultraviolet radiation in chemically untreated rabbit skin.
      A fast jump in EPR signal level, occurring over a few seconds, is observed
      immediately after a skin sample is exposed to UV. This is followed by a slower
      increase toward an elevated steady-state signal over a period of hours as the
      skin is continuously exposed to a UV light source. Upon cessation of UV light
      exposure, EPR signal levels undergo an abrupt drop followed by a slower decay
      toward natural levels. Elevated free radical concentrations following UV exposure
      are found to persist for several hours in whole skin. These results are
      consistent with time-resolved EPR measurements of photoinduced radicals in
      various natural melanins.

PMID- 8570713
TI  - The effect of photodynamic treatment of yeast with the sensitizer chloroaluminum
      phthalocyanine on various cellular parameters.
AB  - Photodynamic treatment of Kluyveromyces marxianus with chloroaluminum
      phthalocyanine resulted in loss of clonogenicity. Several parameters were studied
      to identify targets that could be related to loss of colony-forming capacity.
      Inhibition of various plasma membrane-bound processes was observed, such as
      substrate transport and plasma membrane ATPase activity. Moreover, K+ loss from
      the cells was observed. Photodynamic treatment also reduced the activity of
      various enzymes involved in energy metabolism, thereby decreasing the cellular
      ATP level. It will be discussed however that none of these processes is likely to
      be related directly to loss of clonogenicity. Treatment with phthalocyanine and
      light resulted in a strong inhibition of the incorporation of 14C-phenylalanine
      in trichloracetic acid-precipitable material. The induction of the beta
      galactoside utilization system was also strongly inhibited. The latter two
      processes did not recover during incubation, subsequent to photodynamic
      treatment. It is concluded that photodynamically induced inhibition of protein
      synthesis is a critical factor contributing to the loss of clonogenicity.

PMID- 8570714
TI  - In vitro demonstration of a fundamental difference in the proliferation of murine
      and human bone marrow and lymphocytes following ultraviolet irradiation:
      relevance to bone marrow transplantation.
AB  - Exposure of rodent allogeneic donor marrow and splenocyte grafts to ultraviolet
      radiation (UVR) has been shown to permit durable engraftment at doses that
      abolish graft-versus-host disease (GVHD) and graft rejection. We have compared
      both murine and human alloreactive and mitogen-induced lymphoid responses and
      bone marrow proliferation in mixed lymphocyte culture (MLC), phytohemagglutinin
      (PHA)-induced proliferation and colony-forming unit-granulocyte/macrophage (CFU
      GM) assays using germicidal UVC (200-290 nm), broadband and narrowband UVB (290
      320 nm) and UVA (320-400 nm) sources. Our data show a wavelength and dose
      dependent reduction in lymphoid proliferation in the mouse with CFU-GM survival
      of 50-75% of control at doses required to abolish allogeneic lymphocyte responses
      for all lamps. In contrast, human lymphocyte responses are more resistant to UVC
      with CFU-GM proliferation reduced to zero when allostimulation is abolished.
      Mitogen-induced lymphoid responses show a similar wavelength-dependent
      sensitivity. Abolition of response in MLC using UV-irradiated stimulator cells
      was less sensitive than proliferation with UV-irradiated responder cells at all
      wavelengths in both species. With all sources, murine CFU-GM proliferation is
      less susceptible to UVR than human marrow at doses required to abolish lymphoid
      responses.

PMID- 8570715
TI  - Biodistribution and virus inactivation efficacy of a silicon phthalocyanine in
      red blood cell concentrates as a function of delivery vehicle.
AB  - The silicon phthalocyanine, HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc 4), is a new
      photosensitizer that can inactivate lipid-enveloped viruses in red blood cell
      concentrates (RBCC) upon exposure to red light. Because Pc 4 is insoluble in
      water, it was delivered either as an emulsion in saline and cremophor EL (CRM) or
      as a solution in dimethyl sulfoxide (DMSO). In RBCC, Pc 4 added in either vehicle
      distributed between the plasma and red blood cells (RBC) in a ratio of 4:6,
      similar to the ratio of these components in RBCC 3:7 (i.e. a hematocrit of 70%).
      Light exposure did not affect this distribution and caused only marginal
      degradation of Pc 4 at a light dose that inactivates > 5 log10 vesicular
      stomatitis virus (VSV). Among human plasma proteins, Pc 4 bound mainly (about
      70%) to lipoproteins and to a lesser extent to albumin and lower molecular weight
      proteins when delivered in DMSO. When delivered in CRM, distribution between
      lipoproteins and albumin became more even. Among the lipoproteins Pc 4 bound
      almost exclusively to very low-density lipoproteins (VLDL) when delivered in DMSO
      and to both VLDL and low-density lipoproteins when added in CRM. The rate of VSV
      inactivation was independent of the delivery vehicle but there was less RBC
      damage, as measured by hemolysis during storage, when Pc 4 was added in CRM.
      These results indicate that using CRM as emulsifier can enhance the specificity
      of Pc 4-induced photochemical decontamination of RBCC for transfusion.

PMID- 8570716
TI  - Photodynamically generated 3-beta-hydroxy-5 alpha-cholest-6-ene-5- hydroperoxide:
      toxic reactivity in membranes and susceptibility to enzymatic detoxification.
AB  - Singlet oxygen (1O2)-mediated photooxidation of cholesterol gives three
      hydroperoxide products: 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide (5
      alpha-OOH), 3 beta-hydroxycholest-4-ene-6 alpha-hydroperoxide (6 alpha-OOH) and 3
      beta-hydroxycholest-4-ene-6 beta-hydroperoxide (6 beta-OOH). These species have
      been compared with respect to photogeneration rate on the one hand and
      susceptibility to enzymatic reduction/detoxification on the other, using the
      erythrocyte ghost as a cholesterol-containing test membrane and chloroaluminum
      phthalocyanine tetrasulfonate (AlPcS4) as a 1O2 sensitizer. Peroxide analysis was
      accomplished by high-performance liquid chromatography with mercury cathode
      electrochemical detection (HPLC-EC[Hg]). The initial rate of 5 alpha-OOH
      accumulation in AlPcS4/light-treated ghosts was found to be about three times
      greater than that of 6 alpha-OOH or 6 beta-OOH. Membranes irradiated in the
      presence of ascorbate and ferric-8-hydroxyquinoline (Fe[HQ]2, a lipophilic iron
      complex) accumulated lesser amounts of 5 alpha-OOH, 6 alpha-OOH and 6 beta-OOH
      but relatively large amounts of another peroxide pair, 3 beta-hydroxycholest-5
      ene-7 alpha- and 7 beta-hydroperoxide (7 alpha, 7 beta-OOH), suggestive of iron
      mediated free radical peroxidation. When photoperoxidized membranes containing 5
      alpha-OOH, 6 alpha,6 beta-OOH and 7 alpha,7 beta-OOH (arising from 5 alpha-OOH
      rearrangement) were incubated with glutathione (GSH) and phospholipid
      hydroperoxide glutathione peroxidase (PHGPX), all hydroperoxide species underwent
      HPLC-EC(Hg)-detectable reduction to alcohols, the relative first order rate
      constants being as follows: 1.0 (5 alpha-OOH), 2.0 (7 alpha,7 beta-OOH), 2.4 (6
      alpha-OOH) and 3.2 (6 beta-OOH).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570717
TI  - Modification of alpha-chymotrypsin using a water-soluble photo-Fenton reagent.
AB  - Modification of an enzyme, alpha-chymotrypsin, was examined by using a water
      soluble photo-Fenton reagent. By photoirradiation of the enzyme with the reagent,
      which can occupy a binding site of the enzyme, a tryptophan residue in the
      vicinity of the active site was oxidized to N-formylkynurenine. Concurrently, the
      catalytic properties of the enzyme were largely changed: the Km was increased and
      the kcat was decreased. The decrease in kcat for a specific amide substrate was
      the most significant among the esters and amides examined. The water-soluble
      photo-Fenton reagent would be useful to chemically modify relatively limited
      regions in biomolecules.

PMID- 8570718
TI  - Photochemical reactions of azidocoumarins.
AB  - Photochemical reactions of 6-azidocoumarin and 7-azido-4-methylcoumarin in the
      presence of secondary amines have been investigated for their potential
      applications in photoaffinity labeling. It was found that the singlet nitrene
      generated from 6-azidocoumarin isomerized to a dehydroazepine intermediate that
      reacted with an amine to yield two isomeric adducts. Photolysis of 7-azido-4
      methylcoumarin, in contrast, gave a triplet nitrene that abstracted hydrogen
      atoms from secondary amine molecules to form 7-amino-4-methylcoumarin as the
      major product. The difference in the intersystem crossing rate between the two
      compounds originates from the azido position relative to the carbonyl group.
      Because of its ability to form a covalent linkage with a nucleophile, 6
      azidocoumarin is deemed to have a greater potential as a photoaffinity label than
      7-azido-4-methylcoumarin.

PMID- 8570719
TI  - Influence of combined AC-DC magnetic fields on free radicals in organized and
      biological systems. Development of a model and application of the radical pair
      mechanism to radicals in micelles.
AB  - The effect of an alternating current (AC) magnetic field (MF) on radical behavior
      is identical to that exerted by a direct current (DC) field of the same
      instantaneous strength provided that the frequency is low enough in comparison
      with radical pair dynamics. This criterion is easily met by environmental fields.
      In general, combined AC/DC fields will lead to increased radical concentrations
      and oscillating free radical concentrations. Interestingly, the frequency of
      oscillation for radical concentration seldom follows exactly the pattern of the
      external AC component of the MF. Even the simple case of an AC-only field at 60
      Hz can lead to oscillations in radical concentrations at 120 Hz. The
      concentration time dependence patterns can be even more complex when the singlet
      and triplet levels of the radical pair are not degenerate. Further, the effects
      can change dramatically depending upon the absolute and relative values of the AC
      and DC components, thus providing a possible explanation for MF windows for
      certain effects reported experimentally. Effects on the average radical
      concentration are probably relevant only for fields higher than about 0.1 gauss.
      Oscillating radical concentrations may influence signal transduction processes or
      other cellular mechanisms; at the present time there is not enough knowledge
      available to establish a reasonable threshold for these types of effects. This
      contribution aims at providing a solid foundation to guide the experimentalist in
      the design of meaningful experiments on the possible role of MF perturbations of
      radical chemistry on biological response.

PMID- 8570720
TI  - Autofluorescence spectroscopy of optically trapped cells.
AB  - Cellular autofluorescence spectra were monitored in a single-beam gradient force
      optical trap ("optical tweezers") in order to probe the physiological effects of
      near infrared and UVA (320-400 nm) microirradiation. Prior to trapping, Chinese
      hamster ovary cells exhibited weak UVA-excited autofluorescence with maxima at
      455 nm characteristic of beta-nicotinamide adenine dinucleotide (phosphate)
      emission. No strong effect of a 1064 nm NIR microbeam on fluorescence intensity
      and spectral characteristics was found during trapping, even for power densities
      up to 70 MW/cm2 and radiant exposures of 100 GJ/cm2. In contrast to the 1064 nm
      trap, a 760 nm trapping beam caused a two-fold autofluorescence increase within 5
      min (about 20 GJ/cm2). Exposure to 365 nm UVA (1 W/cm2) during 1064 nm trapping
      significantly altered cellular autofluorescence, causing, within 10 min, a five
      fold increase and a 6 nm red shift versus initial levels. We conclude that 1064
      nm microbeams can be applied for an extended period without producing
      autofluorescence changes characteristic of alterations in the cellular redox
      state. However, 760 nm effects may occur via a two-photon absorption mechanism,
      which, in a manner similar to UVA exposure, alters the redox balance and places
      the cell in a state of oxidative stress.

PMID- 8570721
TI  - Nucleic acid hybridization accompanied with excimer formation from two pyrene
      labeled probes.
AB  - We developed a novel nucleic acid hybridization method based on excimer
      formation. We used two different 16-mer oligonucleotide probes that had a
      combined continuous-sequence run that was complementary to a target 32-mer. Prior
      to hybridization, the adjacent terminal ends (i.e. the 3'-terminal of one probe
      and the 5'-terminal of the other probe) were each labeled with one pyrene
      residue. When these probes simultaneously hybridized to the target, a 495 nm
      broad fluorescence band was produced. The intensity of this band increased as the
      intensity of the pyrene monomer bands decreased, indicating that the 495 nm band
      was attributed to the pyrene excimer. The excimer fluorescence, easily
      differentiated from the monomer bands for emission wavelength, opens up a new way
      to perform homogeneous hybridization assays and in vivo imaging of nucleic acids.

PMID- 8570722
TI  - Ultraviolet action spectra for photobiological effects in cultured human lens
      epithelial cells.
AB  - The action spectrum for cell killing by UV radiation in human lens epithelial
      (HLE) cells is not known. Here we report the action spectrum in the 297-365 nm
      region in cultured HLE cells with an extended lifespan (HLE B-3 cells) and define
      their usefulness as a model system for photobiological studies. Cells were
      irradiated with monochromatic radiation at 297, 302, 313, 325, 334 and 365 nm.
      Cell survival was determined using a clonogenic assay. Analysis of survival
      curves showed that radiation at 297 nm was six times more effective in cell
      killing than 302 nm radiation; 297 nm radiation was more than 260, 590, 1400 and
      3000 times as effective in cell killing as 313, 325, 334 and 365 nm radiation,
      respectively. The action spectrum was similar in shape to that for other human
      epithelial cell lines and rabbit lens epithelial cells. The effect of UV
      radiation on crystallin synthesis was also determined at different wavelengths.
      To determine whether exposure to UV radiation affects the synthesis of beta
      crystallin, cells were exposed to sublethal fluences of UV radiation at 302 and
      313 nm, labeled with [35S]methionine and the newly synthesized beta-crystallin
      was analyzed by immunoprecipitation and western blotting using an antibody to
      beta-crystallin. The results show a decrease in crystallin synthesis in HLE cells
      irradiated at 302 and 313 nm at fluences causing low cytotoxicity. The effect of
      radiation on membrane perturbation was determined by measuring enhancement of
      synthesis of prostaglandin E2 (PGE2). Synthesis of PGE2 occurs at all UV
      wavelengths tested in the 297-365 nm region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570723
TI  - Protection against ultraviolet-B radiation-induced local and systemic suppression
      of contact hypersensitivity and edema responses in C3H/HeN mice by green tea
      polyphenols.
AB  - Exposure of skin to UV radiation can cause diverse biological effects, including
      induction of inflammation, alteration in cutaneous immune cells and impairment of
      contact hypersensitivity (CHS) responses. Our laboratory has demonstrated that
      oral feeding as well as topical application of a polyphenolic fraction isolated
      from green tea (GTP) affords protection against the carcinogenic effects of UVB
      (280-320 nm) radiation. In this study, we investigated whether GTP could protect
      against UVB-induced immunosuppression and cutaneous inflammatory responses in C3H
      mice. Immunosuppression was assessed by contact sensitization with 2,4
      dinitrofluorobenzene applied to UVB-irradiated skin (local suppression) or to a
      distant site (systemic suppression), while double skin-fold swelling was used as
      the measure of UVB-induced inflammation. Topical application of GTP (1-6
      mg/animal), 30 min prior to or 30 min after exposure to a single dose of UVB (2
      kJ/m2) resulted in significant protection against local (25-90%) and systemic
      suppression (23-95%) of CHS and inflammation in mouse dorsal skin (70-80%). These
      protective effects were dependent on the dose of GTP employed; increasing the
      dose (1-6 mg/animal) resulted in an increased protective effect (25-93%). The
      protective effects were also dependent on the dose of UVB (2-32 kJ/m2). Among the
      four major epicatechin derivatives present in GTP, (-)-epigallocatechin-3
      gallate, the major constituent in GTP, was found to be the most effective in
      affording protection against UVB-caused CHS and inflammatory responses. Our study
      suggests that green tea, specifically polyphenols present therein, may be useful
      against inflammatory dermatoses and immunosuppression caused by solar radiation.

PMID- 8570724
TI  - Reduction of interferon-gamma as a critical mechanism by which ultraviolet
      radiation prevents tumor rejection.
AB  - Mice irradiated with UVB, unlike nonirradiated mice, are highly susceptible to
      syngeneic, immunogenic tumors induced by UVB irradiation or by chemicals. We
      postulated that UV induced susceptibility to immunogenic tumors results from a
      reduction in host capacity to generate an interferon (IFN)-gamma immune response
      to tumor antigens. Shaved BALB/c mice were exposed to 6 x 10(5) J m-2 of UVB
      radiation delivered intermittently over 12 weeks. The UVB-irradiated and
      nonirradiated mice received intradermal injections of UVM12 or BP2 tumor cells.
      After 0, 1.5, 3, 7 or 21 days, draining lymph nodes were excised. Lymph node
      cells were incubated with UVM12 or BP2 cells that had received 2.5 Gy of gamma
      radiation. After 48 h in culture, supernatants were analyzed for IFN-gamma
      content by enzyme-linked immunosorbent assay and cellular RNA was extracted for
      mRNA detection by reverse transcriptase-polymerase chain reaction analysis. At 7
      days after tumor injection, draining lymph node cells from nonirradiated control
      mice secreted significant levels of IFN-gamma and contained at least 0.0729 amol
      of IFN-gamma mRNA/microgram cDNA upon in vitro exposure to gamma-irradiated tumor
      cells. Draining lymph node cells removed from UV-irradiated mice contained only
      18% as much IFN-gamma mRNA and secreted little or no IFN-gamma when exposed to
      gamma-irradiated tumor cells. A single injection of antibody directed against
      murine IFN-gamma rendered normal mice as susceptible as UV-irradiated mice to BP2
      tumor cells. Thus, chronic UV irradiation leads to an inability of host tumor
      draining lymph node cells to mount an IFN-gamma response to tumor
      antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570725
TI  - Inactivation of Trypanosoma cruzi trypomastigote forms in blood components by
      photodynamic treatment with phthalocyanines.
AB  - Three phthalocyanine dyes HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc 4),
      HOSiPcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 5) and aluminum tetrasulfophthalocyanine
      hydroxide (AlOHPcS4) were evaluated for their ability to inactivate the
      trypomastigote form of Trypanosoma cruzi in fresh frozen plasma (FFP) and red
      blood cell concentrates (RBCC). The compound Pc 4 was found to be highly
      effective in killing T. cruzi, Pc 5 less effective and AlOHPcS4 ineffective. With
      FFP as the medium, a complete loss of parasite infectivity in vitro (> or = 5
      log10) was found to occur with 2 microM Pc 4 after irradiation with red light (>
      600 nm) at a fluence of 7.5 J/cm2, while with RBCC as the medium, a complete loss
      was found to occur at a fluence of 15 J/cm2. Even without illumination, Pc 4 at 2
      microM also killed about 3.7-4.1 log10 of T. cruzi in FFP during 30 min. Observed
      differences in T. cruzi killing by the various phthalocyanines may related to
      differences in binding; Pc 4 binds to the parasites about twice as much as Pc 5.
      Ultrastructural analysis of treated parasites suggests that mitochondria are a
      primary target of this photodynamic treatment. The data indicate that Pc 4
      combined with exposure to red light could be used to eliminate bloodborne T.
      cruzi parasites from blood components intended for transfusion. The inactivation
      of T. cruzi by Pc 4 in the dark suggests a possible therapeutic application.

PMID- 8570726
TI  - Sites of photodamage in vivo and in vitro by a cationic porphyrin.
AB  - Localization and photodynamic efficacy of a monocationic porphyrin (MCP) were
      assessed using murine leukemia cells in culture. This sensitizer localized at
      surface membrane loci and catalyzed selective photodamage to membrane structures.
      Although both cationic and hydrophobic, this porphyrin was not recognized by the
      multidrug transporter, which excludes many cationic agents from cells that
      express multidrug resistance. Photodynamic studies with the murine radiation
      induced fibrosarcoma tumor model indicated moderate photosensitization of
      neoplastic lesions in vivo at 3 h, but not at 24 h after sensitizer
      administration. Pharmacokinetic studies indicate that plasma levels, not tissue
      levels were the major determinant of photodynamic therapy (PDT) response.
      Consistent with this observation, vascular damage and disturbances of tissue
      perfusion followed PDT. These effects were more pronounced in tumor-bearing skin
      than in normal skin. The therapeutic response to MCP appeared to be related
      mainly to secondary, probably vascular, effects.

PMID- 8570727
TI  - In situ comparison of 665 nm and 633 nm wavelength light penetration in the human
      prostate gland.
AB  - The depth of treatment in photodynamic therapy (PDT) of tumors varies with the
      wavelength of light activating the photosensitizer. New generation
      photosensitizers that are excited at longer wavelengths have the potential for
      increasing treatment depths. Tin ethyl etiopurpurin (SnET2), a promising second
      generation photosensitizer is maximally activated at 665 nm, which may be
      significantly more penetrating than 633 nm light currently used with porphyrins
      in PDT. The penetration of 665 nm and 633 nm wavelength red light in the prostate
      gland was compared in 11 patients undergoing prostatic biopsies for suspected
      prostatic cancer. Interstitial optical fibers determined the light attenuation
      within the prostate gland. Of the 11 patients, 7 had dual wavelength and 4 had
      single wavelength studies. The mean attenuation coefficients, mueff, for 665 nm
      and 633 nm wavelength light were 0.32 +/- 0.05 mm-1 and 0.39 +/- 0.05 mm-1,
      respectively, showing a statistically significant difference (P = 0.0003). This
      represented a 22% increase in the mean penetration depth and at 10 mm from the
      delivery fiber there was 1.8 times as much 665 nm light fluence than 633 nm. The
      mean mueff at 665 nm for benign and malignant prostate tissue were similar (P =
      0.42), however, there was significant interpatient variation (mueff ranging from
      0.24 to 0.42 mm-1) reflecting biological differences of therapeutic importance.
      The enhanced light fluence and penetration depth with 665 nm light should allow
      significantly larger volumes of prostatic tissue to be treated with SnET2
      mediated PDT.

PMID- 8570728
TI  - Cellular fluorescence of the endogenous photosensitizer protoporphyrin IX
      following exposure to 5-aminolevulinic acid.
AB  - Supplying 5-aminolevulinic acid (ALA), a precursor in the biosynthetic pathway to
      heme from an external source leads to an accumulation of the endogenous
      fluorescent photosensitizer protoporphyrin IX (PPIX). Following instillation of
      ALA in the urinary bladder neoplastic tissue can be discerned by fluorescence
      cystoscopy or treated by illumination with light of an appropriate wavelength. In
      order to provide a biological rationale for the clinical findings, we have
      analyzed the capacity of three different cell lines to accumulate PPIX by flow
      cytometry. Three different urothelial cell lines, normal fibroblasts and
      endothelial cells were exposed to ALA under varying conditions. Urothelial cell
      lines J82 and RT4, derived from malignancies of the bladder displayed
      fluorescence intensities 9- and 16-fold, respectively, above the fluorescence
      level of the normal urothelial cell line HCV29. Human umbilical cord endothelial
      cells fluoresced moderately while the fibroblast cell line N1 exhibited a
      fluorescence level comparable to those of the cancer cells. Fluorescence
      increased with increasing cell density and was also dependent on the growth of
      cells as monolayers or multicellular spheroids. Increasing ALA concentrations led
      to saturation of fluorescence after 4 h of incubation at cell type-specific
      fluorescence levels obtained at different ALA concentrations. Continuous
      incubation in medium containing serum resulted in a linear rise of fluorescence
      during the first 4 h, which was followed by a saturation period (8-24 h) and a
      renewed rise. In the case of serum depletion, fluorescence intensities were
      significantly higher and increased linearly during the entire 48 h incubation
      period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570730
TI  - Distribution of 5-aminolevulinic acid-induced porphyrins in noduloulcerative
      basal cell carcinoma.
AB  - Microscopic fluorescence photometry incorporating a light-sensitive thermo
      electrically cooled charge-coupled device (CCD) camera was employed to
      investigate the fluorescence distribution of 5-aminolevulinic acid (ALA)-induced
      porphyrins in 22 patients with a total number of 52 noduloulcerative basal cell
      carcinomas (BCC) after topical ALA application with or without dimethylsulfoxide
      (DMSO)/ethylenediaminetetraacetic acid (EDTA) or after intravenous administration
      of ALA. Both localization patterns and amounts of ALA-induced porphyrins in the
      BCC were studied. The ALA-induced porphyrins were localized only in the
      superficial layers of the noduloulcerative BCC lesions after topical application
      of 20% ALA alone for 3 h. However, both the penetration of ALA into deep lesions
      and the production of the ALA-induced porphyrin fluorescence were increased after
      topical administration of 20% ALA and 20% DMSO/4% EDTA for 3 h. Prior treatment
      with 99% DMSO for 15 min further enhanced the ALA penetration into the BCC
      lesions after topical application of the ALA/DMSO/EDTA mixture and produced more
      ALA-induced porphyrins by a factor of about three compared with those treated
      with ALA alone. The penetration of ALA into the deep BCC lesions could also be
      increased by prolonging the time of topical application of 20% ALA/4% EDTA to 29
      48 h (without DMSO). Intravenous injection of ALA led to a more homogeneous
      distribution of the ALA-derived porphyrins in the whole noduloulcerative BCC
      lesions.

PMID- 8570729
TI  - The validation of a new vascular damage assay for photodynamic therapy agents.
AB  - The therapeutic effect of photodynamic therapy (PDT: photodynamic sensitizer +
      light) is partly due to vascular damage. This report describes a new vascular
      photodamage assay for PDT agents and a validation of the assay. The method
      described here quantitates changes in tissue blood perfusion based on the
      relative amount of injected fluorescein dye in treated and untreated tissues. A
      specially designed fluorometer uses chopped monochromatic light from an argon
      laser as a source for exciting fluorescein fluorescence. The fluorescent light
      emitted from the tissue is collected by a six element fiberoptic array, filtered
      and delivered to a photodiode detector coupled to a phase-locked amplifier for
      conversion to a voltage signal for recording. This arrangement permits a rather
      simple, inexpensive construction and allows for the simultaneous use of the argon
      laser by other investigators. The routine assay for characterizing a specific
      photosensitizer at a standard dose consists of the sequential allocation of eight
      mice to a set of different light doses designed to span the dose-response range
      of fluorescein fluorescence exclusion (measured 8-10 min after fluorescein
      injection). The assay validation experiment used an anionic photosensitizer, 2-[1
      hexyloxyethyl]-2-devinyl pyropheophorbide-a at a dose of 0.4 mumol/kg. The
      parameter estimates (n = 34 mice) from fitting the standard Hill dose-response
      model to the data were: median fluorescence exclusion light dose FE50 = 275 +/-
      8.3 J/cm2 and Hill sigmoidicity parameter m = -3.66 +/- 0.28. Subsets of the full
      data set randomly selected to simulate a standard eight mice experiment yielded
      similar parameter estimates. The new assay provides reliable estimates of PDT
      vascular damage with a frugal sequential experimental design.

PMID- 8570731
TI  - cis-urocanic acid failed to affect in vitro human Langerhans cell allostimulatory
      function.
AB  - Urocanic acid (UCA) represents the major ultraviolet B (UVB, 290-320 nm)
      absorbing component of the skin. Trans-UCA is naturally produced in the stratum
      corneum and converts to the cis isomer upon UVB irradiation. In this study, we
      examined the effect of purified cis-UCA (about 99% of cis isomer) on the human
      Langerhans cell (LC) allostimulatory function by using the mixed epidermal cell
      lymphocyte reaction (MELR). We found that addition of increasing amounts (6.5-400
      micrograms/mL) of purified cis-UCA or trans-UCA did not modify the T-cell
      response supported by enriched LC (eLC: 8-25% LC) as well as purified LC (pLC: 70
      90% LC) suspensions. Because cis-UCA had no effect on the allostimulatory
      function of untreated LC, we investigated whether this compound could modify T
      cell proliferation induced by UVB-irradiated LC. The UVB exposure of eLC or pLC
      to 100 J/m2 significantly inhibited the capacity of both suspensions to mount a T
      cell response. However, addition of cis-UCA did not potentiate this UVB-induced
      immunosuppression. The eLC or pLC were then incubated with cis-UCA for 18 h at 37
      degrees C and washed before adding to allogeneic T cells. The obtained
      proliferative response was similar to that induced by control LC incubated in
      medium alone, demonstrating that pretreatment with cis-UCA did not alter human LC
      function. In conclusion, these results strongly suggest that cis-UCA has no
      direct effect on human LC antigen-presenting function.

PMID- 8570732
TI  - Psoralen-mediated virus photoinactivation in platelet concentrates: enhanced
      specificity of virus kill in the absence of shorter UVA wavelengths.
AB  - Treatments with psoralens and long-wavelength ultraviolet radiation (UVA, 320-400
      nm; PUVA) have shown efficacy for virus sterilization of platelet concentrates
      (PC). Our laboratory has employed the psoralen derivative 4'-aminomethyl-4,5',8
      trimethylpsoralen (AMT), and we have found that platelet integrity is best
      preserved when rutin, a flavonoid that quenches multiple reactive oxygen species,
      is present during AMT/UVA treatment of PC. In this report, we examine the effects
      of different UVA spectra under our standard PC treatment conditions (i.e. 50
      micrograms/mL AMT, 0.35 mM rutin and 38 J/cm2 UVA). Added vesicular stomatitis
      virus (VSV; > or = 5.5 log10) was completely inactivated with the simultaneous
      maintenance of the platelet aggregation response (> 90% of control) when a UVA
      light source with transmission mainly between 360 and 370 nm (narrow UVA1) was
      used. In contrast, with a broad-band UVA (320-400 nm; broad UVA) light source,
      the aggregation response was greatly compromised (< 50% of control) with only a
      minor increase in the rate of VSV kill. With this lamp, platelet function could
      be improved to about 75% of the control by adding a long-pass filter, which
      reduced the transmission of shorter (< or = 345 nm) UVA wavelengths (340-400 nm;
      UVA1). At equivalent levels of virus kill, aggregation function was always best
      preserved when narrow UVA1 was used for PUVA treatment. Even in the absence of
      AMT, and with or without rutin present, narrow UVA1 irradiation was better
      tolerated by platelets than was broad UVA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570733
TI  - Chromophore-assisted laser inactivation of subunits of the T-cell receptor in
      living cells is spatially restricted.
AB  - Chromophore-assisted laser inactivation (CALI) is a molecular photoablation
      technique that has been used to elucidate the in vivo roles of specific proteins
      in neural development. The interpretation of its effects on proteins in living
      cells relies on knowing how spatially restricted the CALI-induced damage is in
      vivo. To determine the spatial specificity of CALI in living cells, we have
      applied CALI to individual subunits of the T-cell receptor (TCR) complex on the
      surface of 2B4 hybridoma cells in culture and have examined the consequent
      structural and functional integrity of the TCR-alpha, TCR-beta and CD3-epsilon.
      The CALI of TCR-beta resulted in the disruption of the beta subunit and also
      resulted in a small effect on antibody binding alone to the neighboring TCR-alpha
      but caused no effect on another subunit, CD3-epsilon. Reciprocal experiments
      directing CALI to TCR-alpha and CD3-epsilon gave consistent results. No effects
      other than a simple loss of function were observed for any of these CALI
      experiments. These data demonstrate the extent of CALI-induced damage within a
      multisubunit complex in living cells and provide greater confidence for the
      future application of this technique to understanding in vivo function of
      proteins during complex cellular processes.

PMID- 8570734
TI  - Functional mapping of the branched signal transduction pathway that controls
      sporulation in Physarum polycephalum.
AB  - Sporulation of starving plasmodia of Physarum polycephalum was found to be
      induced by far-red light, blue light or heat shock, each of which is perceived by
      a different input receptor system. The branched signal transduction pathway was
      mapped and the time-dependent formation of some of its components analyzed.

PMID- 8570735
TI  - An apparatus for studying rapid electrophysiological responses to light
      demonstrated on Arabidopsis leaves.
AB  - An apparatus for making high-resolution measurements of electrophysiological
      changes induced by light in plant cells was constructed. Its main components were
      a xenon arc lamp, an electronic shutter, a liquid light-guide, a computer
      equipped with an analog-to-digital converter and a computer program that
      controlled the shutter and data acquisition. The apparatus was used to examine
      transient changes in membrane potential (Vm) that occur upon illumination in
      Arabidopsis leaves. Light-on induced a transient hyperpolarization of 4 mV after
      a lag time of 0.53 s. It was followed by a much larger transient depolarization
      that peaked 31 s after light-on. The Vm returned to near its original value after
      approximately 3 min. The early changes in Vm have been proposed to result from
      effects of photosynthetically produced ATP on the activities of H(+)-ATPases and
      K+ channels at the plasma membrane. The kinetics of the initial hyperpolarization
      were found to be reasonably consistent with such a mechanism. It is expected that
      the apparatus described here will be useful in future investigations of this and
      other electrophysiological responses to light.

PMID- 8570736
TI  - The photochemistry of human retinal lipofuscin as studied by EPR.
AB  - Fluorescent material generated in the human retina accumulates within lipofuscin
      (HLF) granules of the retinal pigment epithelium (RPE) during aging. We have been
      investigating the possible light-induced contribution of these fluorophores to
      various diseases including age-related macular degeneration. Our studies have
      shown that some of the fluorescent components of HLF are products of the reaction
      of retinaldehyde with ethanolamine and that synthetic mixtures of this reaction
      can serve as a useful model for photophysical studies. Previous research by us
      has demonstrated that irradiation of either natural or synthetic lipofuscin
      resulted in the formation of a triplet state and possibly a free radical. Here
      EPR studies were performed to verify the formation of that radical. The UV
      irradiation of either synthetic or natural human retinal lipofuscin extracts in
      oxygen-free methanol led to the formation of a 5,5-dimethylpyrroline-N-oxide
      (DMPO) spin-trapped carbon-centered radical resulting from either hydrogen atom
      or electron abstraction from solvent molecules. In the presence of oxygen
      superoxide was formed, which was observed as a DMPO adduct. It is concluded that
      certain components of the chloroform-soluble fluorophores of human RPE lipofuscin
      granules and the fluorescent reaction products of retinaldehyde and ethanolamine
      are photophysically similar but not the same. Electron or hydrogen abstraction
      from a substrate by these fluorophores in vivo and the resulting radical products
      may contribute to the age-related decline of RPE function and blue light damage
      in the retina.

PMID- 8570737
TI  - Visible light anaerobic photoconversion of tyrosine sensitized by riboflavin.
      Cytotoxicity on mouse tumoral cells.
AB  - The anaerobic phototransformation of tyrosine under visible light sensitized by
      riboflavin is reported. The cytotoxicity of the anaerobic photoproducts on in
      vitro-cultured myeloid mouse tumoral cells was demonstrated. A radical mechanism
      is proposed. Dityrosine was identified as one of the main anaerobic photoproducts
      by using absorption, emission and 1H-NMR spectra.

PMID- 8570738
TI  - The molecular chaperone function of alpha-crystallin is impaired by UV
      photolysis.
AB  - Buffer solutions of the lens protein gamma-crystallin and the enzymes aldolase
      and liver alcohol dehydrogenase became turbid and formed solid precipitate upon
      exposure to an elevated temperature of 63 degrees C or to UV radiation at 308 nm.
      When alpha-crystallin was added to the protein solutions in stoichiometric
      amounts, heat or UV irradiation did not cause turbidity, or turbidity developed
      much less rapidly than in the absence of alpha-crystallin. Hence, normal alpha
      crystallin functioned as a "molecular chaperone," providing protection against
      both UV and heat-induced protein aggregation. When alpha-crystallin was
      preirradiated with UV at 308 nm, its ability to function as a chaperone vis-a-vis
      both UV and heat-induced aggregation was significantly impaired, but only at
      relatively high UV doses. A major effect of preirradiation of alpha-crystallin
      was to cause interpeptide crosslinking among the alpha A2 and alpha B2 subunits
      of the alpha-crystallin macromolecule. In our experiments alpha-crystallin was
      exposed to UV doses, which resulted in 0.50 and 90% crosslinking as judged by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. alpha-Crystallin
      samples that were 50% and 90% crosslinked gave chaperone protection, which was
      increasingly impaired relative to unirradiated alpha-crystallin. The results are
      consistent with the notion that UV irradiation of alpha-crystallin results in
      loss of chaperone binding sites.

PMID- 8570739
TI  - Subcellular damage kinetics within co-cultivated WI38 and VA13-transformed WI38
      human fibroblasts following 5-aminolevulinic acid-induced protoporphyrin IX
      formation.
AB  - The generation of the photosensitizer protoporphyrin IX (PpIX) in cells can be
      induced by externally applied 5-aminolevulinic acid (ALA), with that bypassing
      the feedback control mechanism. The aim of the present study was to investigate
      the onset of destructive changes in living cocultivated WI38 and VA13-transformed
      WI38 human fibroblasts following ALA incubation, PpIX production and subsequent
      irradiation by white halogen light with a dose of 2.2 kJ/m2. Specific
      fluorescence markers such as 3,3'-dihexyloxacarbocyanine iodide for endoplasmic
      reticulum (ER) staining and dihydrorhodamine for intact mitochondria mapping
      combined with a low light imaging system are a versatile and sensitive tool to
      examine the photoinduced destruction of organelles in living cells, while
      artifacts are minimized. Mitochondria as primary targets of PpIX undergo a
      condensation under irradiation and are finally destroyed. Photodynamic treatment
      induces further a significant decomposition of ER, although PpIX localization
      could not be determined. Initial destabilization and vesiculation of ER is
      followed by a porous network with large cisternae (indicating the breakdown of
      cell integrity and cell/nucleus membrane damage). Normal cocultivated lung
      fibroblasts showed a delay in destruction compared to the transformed WI38-VA13
      cells. The observed decomposition pattern resembles the morphological pattern of
      apoptosis.

PMID- 8570740
TI  - Photodynamic activities and skin photosensitivity of the
      bis(dimethylthexylsiloxy)silicon 2,3-naphthalocyanine in mice.
AB  - The photodynamic therapy (PDT) activity of the bis(dimethylthexylsiloxy)silicon
      2,3-naphthalocyanine (SiNc 8) was evaluated against the EMT-6 tumor implanted
      intradermally in BALB/c mice. The SiNc 8 was formulated in aqueous emulsions
      based on Cremophor EL or Solutol HS 15. The formulation was shown to affect
      plasma clearance and overall pharmacokinetics. Compared to Cremophor, Solutol
      promoted rapid plasma clearance and high liver retention of the dye, combined
      with a slight increase of dye tumor concentrations. The PDT action spectrum for
      tumor response of SiNc 8 in Cremophor (190 mW cm-2, 200 J cm-2, 24 h
      postinjection [p.i.] of 1 mumol kg-1) showed a maximum at 780 nm, which
      corresponds to the absorption maximum of the monomeric dye as well as the in vivo
      maximum change in the "diffuse optical density" produced by the dye. The extent
      of tumor necrosis increased with augmented dye and light doses. Regardless of the
      formulation, at 1 h p.i. of 0.1 mumol kg-1 SiNc 8, PDT efficiency (190 mW cm-2,
      400 J cm-2) was high but accompanied by severe damage to normal tissues, at 24 h
      p.i. PDT resulted in complete tumor regression in 80% of the animals without
      adverse effects to adjacent tissues, while at 72 h p.i. PDT induced no tumor
      response with Cremophor and only a partial response with Solutol. At the latter
      time point, plasma dye clearance was nearly complete while tumor tissue levels
      remained high, suggesting that tumor response correlates with plasma rather than
      tumor dye levels. Skin sensitivity of SKhI mice to solar-simulated radiation was
      lower with SiNc 8 as compared to Photofrin. Our data suggest the potential of
      SiNc 8 as a far-red absorbing photosensitizer in clinical PDT.

PMID- 8570741
TI  - Minimum doses of ultraviolet radiation required to induce murine skin edema and
      immunosuppression are different and depend on the ultraviolet emission spectrum
      of the source.
AB  - Many photo immunological studies have used UV radiation sources that emit
      nonsolar UV spectral energy and UV doses based on nonimmunological endpoints,
      e.g. erythema and skin edema. Interpretation of these data has led to
      misunderstanding when extrapolated to hypothetical effects in humans exposed to
      solar UV. The purpose of this study was to: (1) establish UV dose response
      relationships for murine skin edema and immunosuppression, and (2) determine how
      different UV spectra affect these relationships. Back skin and ear minimum edema
      doses (MEdD) for Kodacel-filtered FS20 sunlamp UV (290-400 nm) were greater than
      two-fold higher than those for unfiltered FS20 sunlamp UV (250-400 nm). Xenon are
      solar simulator UV (295-400 nm) MEdD were > 10-fold higher than those for
      unfiltered sunlamp UV. Back skin and ear MEdD differed two- to five-fold between
      C3H/HeN, SWR/J and HRA/Skh-1 mice. The minimum immunosuppression doses (MISD) in
      C3H mice showed similar UV source spectrum dependence. The solar simulator UV
      MISD was 5.4- and 1.5-fold higher than for unfiltered and Kodacel-filtered
      sunlamp UV MISD, respectively. Furthermore, MISD were from 3- to 50-fold higher
      than the MEdD for the three UV sources. The UV bioeffectiveness spectra indicated
      that UVC energy (250-290 nm) contributed 12% and 18%, respectively, of the total
      skin edema and immunosuppression UV energy. These data demonstrate the
      variability in UV sensitivity among mouse strains, the significant differences
      between murine MEdD and MISD and how these differences are influenced by nonsolar
      regions (below 295 nm) of the UV spectrum.

PMID- 8570742
TI  - Dietary fat modulates immunoresponsiveness in UV-irradiated mice.
AB  - Previous studies have shown that a high level of dietary lipid (corn oil)
      exacerbates UV-carcinogenic expression in hairless mice. Furthermore, it was
      demonstrated that this effect occurs at the postinitiation, or promotion, stage
      of UV-carcinogenesis--a stage believed to be modulated immunologically. Thus, we
      sought to examine the influence of dietary lipid on specific immune parameters at
      various times within a UV-carcinogenic protocol, with the purpose of detecting
      potential relationships to UV carcinogenesis. Hairless mice were fed either a
      high- (12%, wt/wt, corn oil) or low-fat (0.75%, wt/wt, corn oil) diet for 2 weeks
      prior to start of the UV or experimental protocols. Animals were sensitized to
      dinitrochlorobenzene (DNCB) hapten and delayed-type hypersensitivity (DTH) was
      assessed. Delayed-type hypersensitivity was significantly suppressed (P = 0.01)
      in the high-fat group, even before UV irradiation. Although both groups exhibited
      UV-induced suppression of this response, the high-fat group was totally
      suppressed after 3 weeks of UV, whereas the low-fat group exhibited reactivity
      through week 8. The splenic T-lymphocyte (Thy 1.2+) population had declined by
      about 50% at the time of UV termination (11 weeks). Dietary lipid exerted no
      apparent influence upon this T-cell population. However, after 6 weeks of UV, I
      J+ cells (a marker shown to be acquired adaptively by suppressor T lymphocytes)
      began to increase. By week 15 (4 weeks post-UV) I-J+ cells had increased by about
      65% in the high-fat group, twice the % increase that occurred in the low-fat
      group. When UV-induced tumors were transplanted to recipient animals receiving
      various periods (0, 6, 11 weeks) of UV irradiation, no significant differences in
      median tumor rejection times between the two dietary groups occurred at 0 or 6
      weeks. After 11 weeks of UV, the low-fat group exhibited a tumor rejection time
      that was comparable to that of nonirradiated animals, i.e. 21 days. However,
      median tumor rejection time for the high-fat group was greater than 63 days,
      significantly (P = 0.01) longer than that of the low-fat group. Thus, suppression
      of tumor rejection by high fat occurred at a time when high fat had been shown to
      exacerbate carcinogenic expression and when I-J+ cells had markedly increased.
      These data demonstrate that level of dietary lipid modulates immunoresponsiveness
      in UV-irradiated animals and is compatible with the thesis that immune
      suppression may account for the exacerbation of carcinogenic expression elicited
      by high dietary fat.

PMID- 8570743
TI  - Induction and disappearance of thymine dimers in human skin exposed to UVB
      radiation: flow cytometric measurements in replicating and nonreplicating
      epidermal cells.
AB  - We have earlier reported on determining UV-induced DNA damage in murine epidermal
      cell suspensions by flow cytometric analysis of the fluorescence from a
      fluorescein isothiocyanate-labeled antibody (H3) directed against thymine dimers
      (T < > T). Here we present an optimization of the technique for analysis of
      epidermal cell suspensions from 4 mm biopsies from human skin. Cells with
      different DNA contents can easily be distinguished in flow cytometry by the
      intensity of DNA-specific 7-amino-actinomycin D fluorescence. Genuine G2-M-phase
      cells can further be distinguished from cell doublets by pulse-shape
      discrimination. Thus, T < > T levels in individual cells with different DNA
      contents (i.e. G0-G1, S or G2-M phases) can be determined after in vivo exposure
      of human skin to environmentally relevant UVB (280-315 nm) doses. The method was
      applied to measure the decrease of T < > T in nonreplicating cells (G0-G1 phase)
      and replicating cells (S phase or G2-M phase) from seven volunteers exposed to
      twice their minimal erythema dose. The reduction in the average T < > T-specific
      fluorescence at 24 h after exposure was 46% (ranging between 16% and 66%) for the
      G0-G1 cells and 70% (ranging between 37% and 100%) for the S + G2-M cells. The
      difference was statistically highly significant. Determination of individual DNA
      repair capacities with this method can become a convenient diagnostic tool for
      patients with DNA repair disorders, or it may even be used to identify
      individuals with low repair proficiencies and increased risk of developing skin
      cancers.

PMID- 8570744
TI  - The action spectrum for induction of chronic actinic dermatitis is similar to
      that for sunburn inflammation.
AB  - The action spectrum for induction of the abnormal cutaneous response at 24 h in
      the photosensitivity disorder chronic actinic dermatitis (CAD) was determined in
      15 patients and found to be the same in shape as that for normal sunburn in fair
      skinned individuals at 24 h, as determined for 47 control volunteers, although
      displaced in magnitude. This suggests that an endogenous chromophore(s), the same
      as or similar to that/those responsible for human sunburn, may be responsible for
      initiation of the abnormal reaction to irradiation in CAD, and that the putative
      antigen associated with the CAD reaction may be derived from that/those or
      associated molecules.

PMID- 8570745
TI  - Bilirubin phototoxicity to human cells by green light phototherapy in vitro.
AB  - Phototherapy of newborn infants with blue or green light is the most common
      treatment of neonatal hyperbilirubinemia. Using bilirubin bound to human lymphoid
      and basal skin cells we obtained the green light dose dependency of the bilirubin
      phototoxicity to these cell types. Cells (3-5 x 10(6)/mL) were incubated with
      bilirubin complexed to human serum albumin (final concentrations 340 microM
      bilirubin, 150 microM albumin). Under these conditions all cells showed maximum
      binding of bilirubin. Irradiation with broadband green light (lambda max = 512
      nm) over 24 h led to a light dose-dependent population of cells, which contained
      no bilirubin on the cell membrane as determined by Nomarski interference
      microscopy. The light-induced mechanism of the disappearance of bilirubin caused
      lethal membrane damage to the cells (trypan blue exclusion test). The cell kill
      rate increased with the irradiation dose and with the fraction of cells with no
      bilirubin. When 90% of lymphoid cells were bilirubin free, 46% of them were dead
      (using 480 J cm-1 green light). Similar results were obtained with basal skin
      cells. In addition, bilirubin-induced damage of cell membrane and nuclear
      membrane was also shown by transmission electron microscopy. Bilirubin (340
      microM) in the dark led to 5% of the cells being killed. Basal skin cells bind
      2.5 times more bilirubin molecules than lymphoid cells and showed a different
      bilirubin disappearance. Irradiation of bilirubin in carbon tetrachloride with
      514.5 nm laser light showed generation of singlet oxygen via its luminescence at
      1270 nm. These results demonstrate that green light phototherapy of
      hyperbilirubinemia may cause both skin and immune system damage.

PMID- 8570746
TI  - Photoreaction of 5-methoxypsoralen with thymidine and the thymine moiety of
      isolated and Saccharomyces cerevisiae DNA. Characterization and measurement of
      the two cis-syn furan-side monocycloadducts.
AB  - The photoreaction of the furan-side moiety of 5-methoxypsoralen (5-MOP) with
      thymidine used as a DNA model compound was investigated in the dry state. Under
      these conditions, two main fluorescent photoadducts were formed and isolated by
      HPLC. The two modified nucleosides were characterized as the two cis-syn
      diastereoisomers of furan-side monoadducts of 5-MOP to thymidine on the basis of
      spectroscopic measurements including UV, fluorescence, 1H-NMR and circular
      dichroism analysis. The identification and quantification of the latter
      photoproducts within naked DNA exposed to photoexcited 5-MOP were achieved by
      enzymatic digestion completed by HPLC separation and fluorescence detection.
      Similarly, the two cis-syn furan-side monoadducts were found to be formed in the
      DNA of Saccharomyces cerevisiae cells after incubation with 5-MOP and subsequent
      exposure to 365 nm at an incident dose of 38.4 kJ m-2. Under these conditions,
      the rate of induction of two diastereoisomeric photoadducts was as low as one
      modification per 10(6) and 2 x 10(5) bases, respectively.

PMID- 8570747
TI  - New Discoveries within the Pancreatic Polypeptide Family: From Molecules to
      Medicine. APS conference. Newport Beach, California, November 8-11, 1995.
      Abstracts.

PMID- 8570748
TI  - Physiology on the World-Wide Web.

PMID- 8570749
TI  - The training of physiologists for the 21st century.

PMID- 8570750
TI  - [The problem of drug compliance in schizophrenic patients].

PMID- 8570751
TI  - [Neuroleptics and nicotine].
AB  - Excessive smoking is a well know phenomenon in psychiatry. Nicotine, the most
      important content of cigarette tobacco, interacts with several receptors of
      neurotransmitters in the CNS: especially the dopaminergic system appears to be
      relevant in this respect. Nicotine is a potent substance to counteract
      neuroleptic-induced parkinsonism. On the other hand nicotine is possibly a risk
      factor for tardive dyskinesia. Nicotine has enormous therapeutical implications.

PMID- 8570752
TI  - [Which factors modify drug-compliance?].
AB  - Since the extent of medication noncompliance in schizophrenic patients ranges
      between 50 and 60%, evaluation of factors that are associated with noncompliance
      has become an important issue. 197 schizophrenic patients have been interviewed
      with regard to numerous issues: Form and type of medication; information about
      side effects; attitude of patients towards illness and medication. Our data
      suggest that information about benefits and side effects, as well as the attitude
      of patients towards illness and medication play an important role in the
      adherence to the treatment regimen.

PMID- 8570753
TI  - [Long-term administration of benzodiazepines--disease follow-up, sequelae,
      treatment. A retrospective clinical record evaluation of 194 patients].
AB  - Clinical records of all patients treated from 1983 to 1991 in a university clinic
      for lang-term-use of benzodiazepines were examined. Daily intake of
      benzodiazepines began in 80% immediately after the first prescription. At the
      time of admission, 34% reported intake of more than 3 DDD, i.e. more than 30 mg
      of diazepam. In patients 70%, additional abuse of alcohol and/or other
      psychotropic substances was established. Benzodiazepines were the first
      substances abused in 49%. The diagnosis of abuse or dependency was made in 65%
      before admission. Symptoms of organic brain syndrome were described in 30% of all
      records. Symptom leading to first benzodiazepine intake were somatic complaints
      (40%), depressed mood (39%), insomnia (37% and anxiety (24%). Between first
      intake and admission, there was a significant increase in patients with somatic
      complaints, depressed mood and anxiety. After detocification, symptoms leading to
      admission improved in 80% of all patients.

PMID- 8570754
TI  - [Self-assessment of prescribing behavior of psychotropic drugs for children and
      adolescence. Results of a survey of established physicians].
AB  - All registered general practitioners, pediatricians, and neuropsychiatrists of
      lower franconia were asked to fill out a questionnaire regarding the ratio of 0
      20 year old patients with psychiatric symptoms and their prescribing methods of
      psychopharmaca. Neuropsychiatrists treated less children and adolescents with
      psychiatric symptoms than pediatricians or general practitioners. Approximately
      50% of the patients with psychiatric symptoms received psychopharmaca. The most
      frequently prescribed psychopharmaca were neuroleptics and antidepressants,
      followed by phytopharmaca with various ingredients, which were most frequently
      prescribed by general practitioners. The average duration of a
      psychopharmacotherapy was 9 weeks. A great deal of uncertainty regarding the
      prescription of psychopharmaca to children and adolescents has become evident.
      Despite the fact that an enuresis can not be diagnosed before the end of the 5th
      year, it was one of the most frequently treated symptom of the 2-5 year old
      children. On the other hand, approximately one third of all physicians
      principally do not treat children and adolescents with psychopharmaca.

PMID- 8570755
TI  - [Particular aspects of psychiatric management of mentally retarded patients with
      psychiatric disorders].
AB  - Relevant specific problems of psychiatric disorders in mentally retarded
      individuals are described and discussed on the basis of selected literature.
      Mentally retarded individuals with mental problems differ significantly from
      their normal intelligent counterparts with respect to biological, social and
      psychological aspects. The improvement of the psychiatric-psychotherapeutic care
      seems to be necessary.

PMID- 8570756
TI  - [Coping strategies and stress of family and follow-up of schizophrenia].
AB  - This empirical study including 32 families of schizophrenic patients (DSM-III-R)
      investigates the connection of distress and coping strategies of relatives,
      expressed emotion, distress of patients caused by family life and their
      influences on the course of schizophrenia with the focus on their prognostic
      values. One major issue is the question about distress factors and coping
      behavior of low- und high-EE-families. Using the Munsteraner Familienbogen every
      single family was visited at home after discharge and interviewed. The interview
      targeted especially the coping behavior of relatives.

PMID- 8570757
TI  - [Providing and maintaining jobs for psychiatric patients--how can it be done?].
AB  - An innovative project has produced some good results in the placement of
      psychically disabled people in the general labour market. The "foster colleague
      model" provides support for the client directly at her or his place of work by a
      specially trained member of company staff (the "foster colleague"). This method
      has so far managed to provide 18 formerly psychically ill people with employment
      and helped to keep them in work.

PMID- 8570758
TI  - [Toxic tricyclic drug plasma level caused by fluoxetine].
AB  - A case study illustrates that even after discontinuation fluoxetine still
      increases amtitriptyline plasma-levels. This is caused by an inhibition of the
      metabolism of tricyclics by fluoxetine which was still active due to the long
      elimination half-life of this substance and its metabolite.

PMID- 8570759
TI  - [Perception in melancholia (endogenous depression)].

PMID- 8570760
TI  - [Discussion: has social psychiatric service reached an end?].

PMID- 8570761
TI  - ["Depression and benzodiazepine dependence in the elderly"].

PMID- 8570762
TI  - Effect of initial treatment with antidepressants as a predictor of outcome after
      8 weeks.
AB  - Most findings of antidepressant treatment prediction have not been replicated,
      and this applies to biological predictors as well as sociodemographic and early
      course predictors. One exception might be early psychopathological improvement.
      To reevaluate this question, we examined the results of two large-scale
      controlled clinical trials comparing the selective and reversible inhibitor of
      monoamine oxidase type A (MAO-A) brofaromine with the standard tricyclic compound
      imipramine. One trial was carried out in a normal-aged patient group; the other,
      in elderly patients. Above all, we were interested in determining whether early
      treatment course would prove predictive of later outcome. The main finding was
      that the initial antidepressant effect (measured after 1 and 2 weeks) predicted
      longer term outcome. Although this association was not as strong in the elderly
      patient group, its predictive value did possess a certain clinical relevance.

PMID- 8570763
TI  - Platelet paroxetine binding in major depressive disorder with and without
      comorbid obsessive-compulsive disorder.
AB  - Platelet 3H-paroxetine binding measures were compared in three age-matched groups
      each containing 11 individuals: a group with DSM-III-R major depressive disorder
      (MDD) and comorbid obsessive-compulsive disorder (OCD), a group with DSM-III-R
      MDD alone, and a psychiatrically screened normal comparison group. No differences
      were found between groups in Bmax values. The patients with MDD only were found
      to have significantly higher Kd values than either the group with comorbid OCD or
      the normal subjects. No significant correlations were found between binding
      measures and either depressive or OCD symptoms. Our data suggest that
      inconsistencies remain in the literature on 3H-imipramine binding in OCD and that
      a variety of confounding factors may explain them. Duration of illness, for
      example, may be one such factor as decreases in uptake site number tend to
      dissipate with longer duration of illness.

PMID- 8570765
TI  - A comparison of Tridimensional Personality Questionnaire dimensions in bipolar
      disorder and unipolar depression.
AB  - The harm avoidance (HA) personality dimension has been hypothesized to be a
      vulnerability factor for unipolar depression (UD) but not for bipolar disorder
      (BD). The reported difference on HA scores between these diagnostic groups may
      have been compromised by the assessment of BD patients who had not fully
      recovered. To test the diagnostic specificity of elevated HA scores and to
      elucidate whether assumptions about differences between patients with UD or BD
      might be attributed to the lingering effects of mood state, the Tridimensional
      Personality Questionnaire (TPQ) was administered to recovered patients with
      either BD or UD and a nonpatient comparison group. Both patient groups scored
      higher on the HA dimension than the nonpatient comparison group, but the patient
      groups did not differ from one another on this dimension. Moreover, novelty
      seeking (NS) scores were elevated in subjects with BD compared with both UD
      patients and nonpatient subjects. These results suggest that high HA scores may
      be associated with a mood disorder diagnosis, whereas high NS scores may be
      associated with the BD subtype.

PMID- 8570764
TI  - Effects of intravenous diazepam pretreatment on lactate-induced panic.
AB  - The psychological and physiological effects of acute low-potency benzodiazepine
      administration on lactate-induced panic were examined in 10 patients with panic
      disorder (PD). The patients, who had panicked during a standard sodium-lactate
      infusion, underwent a repeat infusion modified by pretreatment with intravenous
      diazepam (5 mg). Acute Panic Inventory (API) scores preceding the second lactate
      infusion, which were associated with diazepam pretreatment, were significantly
      reduced in compared with those measured before the first lactate infusion.
      However, the second visit "fear of doom" item of the API was significantly
      reduced relative to the same time point of the first visit 35 min before lactate
      infusion, when diazepam had not yet been administered. Thus, the reduction of
      prelactate anxiety preceding the second infusion appeared to reflect both
      pharmacological and nonpharmacological contributions. The diazepam pretreatment
      condition was associated with a significantly increased infusion duration and a
      significant attenuation of rate of API symptom increase in response to lactate.
      Despite significant attenuation of lactate infusion effects associated with the
      diazepam pretreatment condition, 7 of 10 patients experienced a second panic
      attack. This pilot study suggests that diazepam pretreatment is associated with a
      marked reduction of symptomatic response during a second lactate infusion,
      although the magnitude of attenuation observed was insufficient to block lactate
      induced panic in a majority of lactate-vulnerable PD patients.

PMID- 8570766
TI  - Urinary excretion of bufotenin (N,N-dimethyl-5-hydroxytryptamine) is increased in
      suspicious violent offenders: a confirmatory study.
AB  - We previously reported that violent offenders with paranoid symptoms or whose
      violent actions had been directed against family members had higher urinary
      levels of bufotenin than other violent offenders. In the present study, patients
      were evaluated with the Karolinska Scales of Personality (KSP), and urinary
      levels of bufotenin were determined by mass spectrometry. In drug-free patients
      suspiciousness was positively correlated, and socialization was negatively
      correlated, with urinary bufotenin excretion. These two personality variables
      were strongly interdependent. In drug users, bufotenin excretion was correlated
      positively with social desirability and negatively with irritability, but not
      with suspiciousness. Bufotenin excretion was not found to be associated with
      violence toward family members in the present study. The results are in keeping
      with the earlier finding that violent offenders with paranoid personality traits
      have higher urinary levels of bufotenin than other violent offenders.

PMID- 8570767
TI  - Serotonin function in detoxified heroin abusers: prolactin and cortisol responses
      to fenfluramine challenge.
AB  - The function of the central serotonergic system was examined indirectly through
      the measurement of prolactin (PRL) and cortisol responses to fenfluramine
      challenges in 27 heroin addicts 2 months after detoxification and in nine healthy
      volunteers. Heroin abusers included nine addicts with comorbid depressive
      disorders (Group A), nine with aggressive behavior and antisocial personality
      (Group B), and nine with heroin addiction uncomplicated by other Axis I and II
      psychiatric disorders (Group C). PRL and cortisol responses of patients in Group
      A were blunted, while those of patients in Groups B and C did not differ from
      those of the healthy volunteers. Cortisol responses in Group A differed
      significantly from those in the other patient groups and in the normal comparison
      group for AUC analyses, but the diagnosis x time interaction showed a significant
      difference only between Group A and the normal group. Our data suggest that the
      function of the serotonergic system is impaired in heroin addicts with comorbid
      depression but not in heroin addicts who are not clinically depressed. Thus, the
      serotonergic system does not appear to be impaired by prolonged opioid exposure,
      per se.

PMID- 8570768
TI  - Induction of depersonalization by the serotonin agonist meta
      chlorophenylpiperazine.
AB  - Sixty-seven subjects, including normal volunteers and patients with obsessive
      compulsive disorder, social phobia, and borderline personality disorder, received
      ratings of depersonalization after double-blind, placebo-controlled challenges
      with the partial serotonin agonist meta-chlorophenylpiperazine (m-CPP). Challenge
      with m-CPP induced depersonalization significantly more than did placebo.
      Subjects who became depersonalized did not differ in age, sex, or diagnosis from
      those who did not experience depersonalization. There was a significant
      correlation between the induction of depersonalization and increase in panic, but
      not nervousness, anxiety, sadness, depression, or drowsiness. This report
      suggests that serotonergic dysregulation may in part underlie depersonalization.

PMID- 8570769
TI  - Intracerebroventricular injection of phospholipase A2 inhibits apomorphine
      induced locomotion in rats.
AB  - Phospholipase A2 (PLA2) is a key enzyme in phospholipid metabolism. In neurons,
      membrane-bound PLA2 plays an essential role in signal transduction by affecting
      neurotransmitter release and receptor sensitivity. There are some reports of
      increased PLA2 activity in schizophrenia. We investigated the effects of
      intracerebroventricular (i.c.v.) injections of PLA2 on dopamine-mediated behavior
      in rats. Ten days after i.c.v. injection, PLA2 significantly inhibited
      apomorphine-induced locomotion as compared with i.c.v. saline injections. The
      inhibition of apomorphine-induced locomotion by PLA2 was reversible within 4
      weeks after stereotaxic surgery. These findings suggest a functional inhibition
      of dopaminergic postsynaptic receptors by PLA2. Accelerated phospholipid
      metabolism and reduced dopaminergic activity in the prefrontal cortex have been
      postulated to play a role in schizophrenia. Increased PLA2 activity may be
      related to both abnormalities and could thus play a role in the pathophysiology
      of schizophrenia.

PMID- 8570770
TI  - Decreased urinary peptide excretion in schizophrenic patients after neuroleptic
      treatment.
AB  - Six schizophrenic patients had their urinary peptide levels measured before and
      after 5 weeks of treatment with neuroleptic medications. For two patients, levels
      were also measured after a reduction in the neuroleptic dose. Because of the
      heterogeneity of peptide peaks with the same bioactivity, the overall peptide
      levels were compared to initial levels. A neuroleptic effect on peptide levels
      was demonstrated. Several research groups have reported enzyme induction caused
      by neuroleptics in vivo.

PMID- 8570771
TI  - Intracranial meningiomas: correlation of peritumoral edema and psychiatric
      disturbances.
AB  - Patients with proven intracranial meningioma were reexamined for psychiatric
      morbidity. Distribution according to type of meningioma was as follows: 72%
      convexity meningiomas and 28% base-of-skull meningiomas. No psychiatric disorders
      were diagnosed in the nonconvexity group in contrast to 44% in the convexity
      meningiomas. Among the convexity meningiomas, no difference between right- and
      left-hemispheric locations was found. Psychiatric comorbidity in the right
      hemisphere group was found only in patients with frontal lobe meningiomas. Edema
      width was measured on all computed tomographic scan slices on which it appeared,
      and the average of all the slices was calculated. No correlation was found
      between neurological symptoms and edema severity. A statistically significant
      correlation was found between edema volume and the presence of coexisting
      psychiatric disorders, but not between the tumor's mass volume and the
      psychiatric symptoms.

PMID- 8570772
TI  - Pindolol pretreatment blocks stimulation by meta-chlorophenylpiperazine of
      prolactin but not cortisol secretion in normal men.
AB  - Previous reports from this laboratory have shown that pindolol, a partial
      serotonin1A receptor agonist, inhibited prolactin, but not cortisol secretion
      induced by administration of the serotonin (5-HT) precursor L-5-hydroxytryptophan
      or the direct-acting 5-HT2A/5HT2C receptor agonist MK-212. The findings suggest
      additive or interactive effects of 5-HT1A and 5-HT2A/5-HT2C receptors in
      modulating 5-HT-related prolactin, but not cortisol, responsivity. To examine
      further the role of 5-HT1A and 5-HT2A/5-HT2C receptors in prolactin and cortisol
      secretion in healthy men, the effects of meta-chlorophenylpiperazine (mCPP), a
      potent 5-HT receptor agonist, on the above hormones were studied in eight healthy
      men with and without pindolol pretreatment. It has previously been demonstrated
      that ketanserin, a 5-HT2A antagonist, and ritanserin, a 5-HT2A/5-HT2C antagonist,
      block the prolactin and attenuate the hypothalamic-pituitary-adrenal axis
      responses to mCPP in man or rodents. Administration of mCPP induced a significant
      increase in plasma concentrations of prolactin and cortisol. The mCPP-induced
      prolactin concentrations were significantly blocked by pretreatment with
      pindolol, whereas mCPP-stimulated cortisol levels were not diminished by pindolol
      pretreatment. Thus, mCPP-induced prolactin secretion appears to require the
      availability of both 5-HT2C and 5-HT1A receptor activation, since blockade of
      either of these receptors may diminish the mCPP-induced prolactin response.
      Cortisol secretion stimulated by mCPP may occur following 5-HT2C receptor
      stimulation in the presence of 5-HT1A receptor blockade.

PMID- 8570773
TI  - No antidepressant effect of biperiden compared with placebo in depression: a
      double-blind 6-week clinical trial.
AB  - Depression may result from an increased ratio of cholinergic to aminergic central
      neurotransmission. The effect of centrally active anticholinergic agents on
      depressive ratings in depressed patients, however, has not been well studied. In
      a previous open label 4-week clinical trial, Kasper et al. (1981) reported that
      biperiden (Akineton) had antidepressant effects in depressed patients. We
      compared the effects of placebo and biperiden in a randomized, double-blind,
      parallel-design 6-week study. All patients received placebo for the first week
      and then received either biperiden (< or = 12 mg/day) or a peripherally acting
      anticholinergic agent, glycopyrrolate (Robinul, 1 mg/day) for 4 weeks. All
      patients received placebo during week 6. Both groups significantly improved, but
      biperiden did not demonstrate any significant benefit compared with
      glycopyrrolate. In a subgroup of patients receiving biperiden, the percentage of
      rapid eye movement sleep was significantly decreased only in the first week of
      biperiden compared with the initial placebo week, suggesting that tolerance to
      the central effects of biperiden developed. Further studies would be needed to
      determine whether anticholinergic agents possess antidepressant properties.

PMID- 8570774
TI  - L-deprenyl and physostigmine for the treatment of Alzheimer's disease.
AB  - The present study evaluated the safety of and obtained preliminary data on the
      cognitive effects of L-deprenyl and physostigmine in patients with Alzheimer's
      Disease. Seventeen outpatients with Alzheimer's Disease participated in a double
      blind crossover study in which they received 4 weeks of L-deprenyl at a dose of
      10 mg p.o., q.d., and 4 weeks of placebo in random order. During both the L
      deprenyl and placebo periods, patients received cognitive assessments during
      physostigmine (0.5 mg) and placebo infusions separated by 2 days. The cognitive
      effects of these agents alone and in combination were measured with digit span,
      verbal fluency, list learning, praxis, delayed recall, and delayed recognition
      tasks. Fifteen patients completed the study. The two drugs, used alone or in
      combination, were safe and well tolerated. Analyses of variance demonstrated that
      neither physostigmine nor L-deprenyl, whether given alone or in combination,
      significantly improved cognition, when compared with the double placebo
      condition.

PMID- 8570775
TI  - Low-dose naltrexone effects on plasma chemistries and clinical symptoms in
      autism: a double-blind, placebo-controlled study.
AB  - The effect of month-long naltrexone (NTX) treatment at a daily oral dose of 0.5
      mg/kg/day was contrasted with placebo (PLC) in a double-blind study with conjoint
      clinical and biochemical evaluations of therapeutic effects. Modest clinical
      benefits were achieved with both PLC and NTX, with marginally better overall
      results following NTX, and degree of improvement appeared to be related to plasma
      chemical profiles. Massively elevated levels of beta-endorphin were observed in
      all children with assays using C-terminal antibody but not with an N-terminal
      antibody assay. In addition, 70% of the children exhibited abnormally low levels
      of adrenocorticotropic hormone, and smaller subsets exhibited elevated
      norepinephrine (60%), arginine-vasopressin (50%), and serotonin (20%). The best
      clinical responders exhibited the clearest normalization of the elevated plasma
      chemistries, especially in C-terminal-beta-endorphin and serotonin. There was
      some evidence of therapeutic carry-over effects in both clinical and biochemical
      measures in those children who received NTX before PLC. The results suggest that
      NTX only benefits a subgroup of autistic children, who may be identified by the
      presence of certain plasma abnormalities. These results suggest a possible
      linkage between abnormal plasma chemistries, especially those related to the pro
      opiomelanocortin system, and autistic symptoms.

PMID- 8570776
TI  - Placebo-controlled acute dosage naltrexone study in young autistic children.
AB  - In a double-blind, placebo-controlled crossover trial 23 autistic children were
      treated with a single 40-mg dose of the opiate antagonist naltrexone. Drug
      effects were monitored by detailed playroom observations, actometers, and
      parents' checklist ratings (Aberrant Behavior Checklist, social items and target
      behaviors). Naltrexone treatment failed to produce significant changes in social
      behavior, but it did reduce irritability and target scores on behavior
      checklists. The playroom data indicated that naltrexone significantly affected
      indices of activity and attention.

PMID- 8570777
TI  - Alterations in plasma prolyl endopeptidase activity in depression, mania, and
      schizophrenia: effects of antidepressants, mood stabilizers, and antipsychotic
      drugs.
AB  - The activity of prolyl endopeptidase (PEP), a serine proteinase, has been found
      to be significantly lower in the blood of patients with major depression than in
      normal volunteers. The present study investigates plasma PEP activity in 25 major
      depressed, 10 manic, and 14 schizophrenic subjects versus 30 normal volunteers.
      It also examines the effects of antidepressants, valproate, and neuroleptic drugs
      on plasma PEP activity. PEP activity was significantly lower in major depressed
      subjects than in normal volunteers and in patients with mania and schizophrenia.
      In depressed subjects, plasma PEP activity was significantly increased during
      treatment with antidepressant drugs, such as fluoxetine. Plasma PEP activity was
      significantly increased in manic and schizophrenic subjects compared with normal
      volunteers. In manic subjects, short-term treatment with valproate had a
      significant suppressive effect on PEP activity. No significant effects of
      neuroleptics on PEP activity could be found in the schizophrenic patients. The
      results support the hypothesis that lower PEP activity could play a role in the
      pathophysiology of major depression, while increased PEP activity may be related
      to psychotic conditions, such as mania and schizophrenia.

PMID- 8570778
TI  - Cognitive disorders in the positive, negative, and disorganization syndromes of
      schizophrenia.
AB  - Recent factor-analytic studies have derived several trisyndromic models for
      schizophrenia, all based on the positive, negative, and disorganization
      syndromes. The goal of this study was to examine cognitive disorders in these
      three schizophrenic syndromes. The study group was composed of 40 schizophrenic
      patients consecutively admitted to the hospital due to a recrudescence of their
      symptomatology. They were selected on the basis of a semistructured interview,
      diagnosed with DSM-III-R criteria, and evaluated with scales for positive and
      negative symptoms. Their cognitive disorders were assessed with a battery of
      neuropsychological tests. The schizophrenic syndromes were weakly associated with
      cognitive performance through direct correlations and after correction for
      confounding variables. The disorganization and negative syndromes were more
      strongly associated with cognitive disturbances than was the positive syndrome,
      and both were associated with disturbances of visual-motor processes. Moreover,
      the disorganization syndrome was associated with disturbances in language and
      verbal memory and in time-controlled performance.

PMID- 8570779
TI  - Japan-U.S. comparison of responses to depression scale items among adult workers.
AB  - The operating characteristics of the Center for Epidemiologic Studies Depression
      Scale were compared between Japanese and U.S. adult workers. Data were analyzed
      from age- and education-matched male white collar workers (n = 368 for each)
      selected from 2016 workers in Japan and 3059 in the United States. The U.S. data
      were obtained from the 1974-75 Augmentation Survey of the National Health and
      Examination Survey I. The Japanese responses to positively worded items markedly
      differed from those of U.S. workers, whereas responses to negatively worded items
      were generally comparable in the two groups. Thus, spuriously higher positive
      subscale and whole scale scores were found among the Japanese workers compared
      with U.S. workers (mean scores: 6.03 vs. 1.83 for the positive subscale and 9.94
      vs. 5.35 for the whole scale, respectively; both differences were statistically
      significant). Negative subscale scores did not differ significantly in the two
      samples (3.91 vs. 3.52). The present study confirmed the hypothesis of Iwata et
      al. that Japanese respondents have a tendency to suppress the expression of
      positive affect.

PMID- 8570780
TI  - Quantitative electroencephalographic analyses in cocaine-preferring polysubstance
      abusers during abstinence.
AB  - Quantitative electroencephalographic (QEEG) analyses are presented for a group of
      90 subjects recovering from polysubstance abuse (median = 90 days abstinent) who
      preferentially used cocaine. QEEGs showed significant decreases from normal in
      both absolute and relative delta power and decreased theta power in both absolute
      and relative power. Significantly increased relative but not absolute alpha and
      beta power was found. Asymmetry of frontal delta, theta, and alpha power differed
      from normal with right power greater than left. Globally, reduced
      interhemispheric coherence was found in delta and theta bands and frontally in
      the beta band. An atypical EEG pattern was observed in about half of the
      subjects. This was a paroxysmal-like EEG alpha pattern reminiscent of vertex
      waves typically associated with drowsiness but lacking the waxing and waning of
      alpha and the slow lateral eye drift associated with drowsiness.

PMID- 8570781
TI  - Changes of brain anatomy in patients with posttraumatic stress disorder: a pilot
      magnetic resonance imaging study.
AB  - No abnormalities in magnetic resonance images were recorded in patients with
      posttraumatic stress disorder other than an increased incidence (50%) of a small
      cleft in the callosal-septal interface, a cavum of the septum pellucidum. A
      similar grade of cavum was obtained in 14% of normal volunteers matched for age,
      socioeconomic background, and military experience. The cavum is believed to have
      antedated the disorder and is conceived to be a neurodevelopmental aberration.
      The possibility that the cavum is a marker of vulnerability to stress in
      psychopathology is discussed.

PMID- 8570782
TI  - Serum cholinesterase in obsessive-compulsive disorder.
AB  - Levels of serum cholinesterase (PsChe) were measured in 32 drug-free patients
      with obsessive-compulsive disorder (OCD) and 32 sex- and age-matched healthy
      normal volunteers. No significant differences between OCD patients and normal
      subjects were found in PsChe levels. A significant positive correlation between
      patients' PsChe levels and the severity of anxiety, as measured by the Hamilton
      Rating Scale for Anxiety, was found, in agreement with the hypothesis of a
      relationship between state anxiety and PsChe activity. In contrast to findings in
      other reports, PsChe levels significantly increased after 10 weeks of
      antiobsessional pharmacological treatment, underscoring the potential influence
      of drugs on PsChe activity.

PMID- 8570783
TI  - Loss of vision during the retinal stabilization of letters.
AB  - Upper- and lower-case letters of the alphabet were stabilized until loss of
      vision occurred. Loss of straight-line visibility was the most frequently
      reported perceptual event. Occasionally, features of letters separated spatially
      before their loss of visibility. In both instances, loss of visibility often
      resulted in the perception of a less complex letter. Confidence ratings for each
      loss of letter visibility indicated that participants were quite certain about
      perceived fragmentations. In a control experiment, participants were asked to
      guess how letters would fragment during stabilization. Again, loss of line
      visibility was the most frequently reported event. However, spatial separation of
      features was rarely predicted and complex letters were not predicted to fragment
      into simpler letter forms. Furthermore, the confidence in predicted fragmentation
      was quite low. These results are consistent with the view that losses of
      visibility during retinal stabilization constitute a distinct perceptual
      experience. Fragmentations appear to be determined by the availability of less
      complex letter forms and by the loss of subletter information, consisting of
      letter features and information specifying spatial configurations.

PMID- 8570784
TI  - Saccadic suppression relies on luminance information.
AB  - To determine whether saccadic suppression of image displacement uses information
      from luminance channels, we measured spatial displacement detection thresholds
      with equiluminant and non-equiluminant targets during saccades. We compared these
      saccadic thresholds with displacement thresholds measured during fixation by
      making ratios of saccadic thresholds to fixation thresholds. Ratios were lower in
      the equiluminant condition than in the non-equiluminant. This surprising result
      indicates that detection of equiluminant target displacements during saccades was
      better than detection of nonequiluminant targets, compared with the detection
      abilities during fixation. Thus, saccadic suppression of image displacement,
      which should increase displacement thresholds during saccades over fixation
      thresholds, was more effective with nonequiluminant targets. Because of target
      flicker, displacement thresholds were anisotropic in the nonequiluminant
      condition; thresholds were greater when target and eye moved in the same
      direction than when they moved in opposite directions, consistent with earlier
      results. These two effects (flicker-induced anisotropy and greater suppression in
      nonequiluminance) canceled when the eye moved opposite the displacement, yielding
      equal thresholds and summed when eye and target moved in the same direction,
      yielding large threshold differences. We conclude that saccadic suppression of
      image displacement uses mechanisms sensitive to luminance contrast.

PMID- 8570785
TI  - Visual stability with goal-directed eye and arm movements toward a target
      displaced during saccadic suppression.
AB  - This experiment tested whether the perceived stability of the environment is
      altered when there is a combination of eye and visually open-loop hand movements
      toward a target displaced during the eye movements, i.e., during saccadic
      suppression. Visual-target eccentricity randomly decreased or increased during
      eye movements and subjects reported whether they perceived a target displacement
      or not, and if so, the direction of the displacement. Three experimental
      conditions, involving different combinations of eye and arm movements, were
      tested: (a) eye movements only; (b) simultaneous eye and rapid arm movements
      toward the target; and (c) simultaneous eye and arm movements with a restraint
      blocking the arm as soon as the hand left the starting position. The perceptual
      threshold of target displacements resulting in an increased target eccentricity
      was greater when subjects combined eye and arm movements toward the target
      object, specially for the no-restraint condition. Subjects corrected most of
      their arm trajectory toward the displaced target despite the short movement times
      (average MT = 189 ms). After the movements, the null error feedback of the hand's
      final position presumably overlapped the retino-oculomotor signal error and could
      be responsible for the deficient perception of target displacements. Thus,
      subjects interpreted the terminal hand positions as being within the range of the
      endpoint variability associated with the production of rapid arm movements rather
      than as a change of the environment. These results suggest that a natural
      strategy adopted for processing spatial information, especially in a competing
      situation, could favour a constancy tendency avoiding systematic perception of a
      change of environment for any noise or variability at the central or peripheral
      levels.

PMID- 8570786
TI  - Perceptual scaling of synthesized musical timbres: common dimensions,
      specificities, and latent subject classes.
AB  - To study the perceptual structure of musical timbre and the effects of musical
      training, timbral dissimilarities of synthesized instrument sounds were rated by
      professional musicians, amateur musicians, and nonmusicians. The data were
      analyzed with an extended version of the multidimensional scaling algorithm
      CLASCAL (Winsberg & De Soete, 1993), which estimates the number of latent classes
      of subjects, the coordinates of each timbre on common Euclidean dimensions, a
      specificity value of unique attributes for each timbre, and a separate weight for
      each latent class on each of the common dimensions and the set of specificities.
      Five latent classes were found for a three-dimensional spatial model with
      specificities. Common dimensions were quantified psychophysically in terms of log
      rise time, spectral centroid, and degree of spectral variation. The results
      further suggest that musical timbres possess specific attributes not accounted
      for by these shared perceptual dimensions. Weight patterns indicate that
      perceptual salience of dimensions and specificities varied across classes. A
      comparison of class structure with biographical factors associated with degree of
      musical training and activity was not clearly related to the class structure,
      though musicians gave more precise and coherent judgments than did non-musicians
      or amateurs. The model with latent classes and specificities gave a better fit to
      the data and made the acoustic correlates of the common dimensions more
      interpretable.

PMID- 8570787
TI  - A computational model of the Simon effect.
AB  - Even though stimulus location is task irrelevant, reaction times are faster when
      the location of the stimulus corresponds with the location of the response than
      when it does not. This phenomenon is called the Simon effect. Most accounts of
      the Simon effect are based on the assumption that it arises from a conflict
      between the spatial code of the stimulus and that of the response. In this paper
      a computational model of this hypothesis is presented. It provides a
      computationally explicit mechanism of the Simon effect. Consistent with human
      performance, the model provides reaction times that indicate both an advantage
      for the ipsilateral, corresponding response (i.e., facilitation) and a
      disadvantage of the contralateral, noncorresponding response (i.e., inhibition).
      In addition, the model accounts for the fact that the size for the effect depends
      on task difficulty.

PMID- 8570788
TI  - The timing effect of accent production in synchronization and continuation tasks
      performed by musicians and nonmusicians.

PMID- 8570789
TI  - Working memory in older subjects: dealing with ongoing and stored information in
      language comprehension.
AB  - The purpose of this experiment was to investigate the role of aging in working
      memory (WM), or at least the part involved in language comprehension, e.g., a
      double function of processing the ongoing information and keeping in memory the
      product of this processing. Young and older subjects were asked to simultaneously
      detect incongruities in sentences and keep increasing longer series of words (3,
      4, or 5) in memory. The difficulty of incongruity detection was manipulated by
      variation of the number of intervening words (0, 6, or 12) between two critical
      words. Incongruity detection was assumed to be linked to the processing of
      information function of working memory. The concurrent mnemonic load consisted of
      material previously processed, and was assumed to be linked to the storage
      function of WM. Results showed that an increment in incongruity-detection
      difficulty led to a greater decrement in accuracy in older than in young
      subjects, indicating an impairment in the information-processing function. On the
      other hand, an increment in concurrent mnemonic load led to a slightly smaller
      decrement in accuracy in older subjects. Furthermore, fewer words from this
      mnemonic load were recalled in older subjects. It is suggested that older
      subjects are impaired in coping with both requirements of the task, and tend to
      sacrifice the storage of information recently processed to devote their resources
      to the immediate processing component of the task. These results are discussed in
      relation to their implications for language comprehension.

PMID- 8570790
TI  - Blood pressure publication guidelines. Society for Psychophysical Research.
AB  - Blood pressure is one of the most commonly recorded functions in physiology and
      medicine, and it has become a major variable in recent psychophysiological and
      behavioral medicine research. Many methods have been developed for the
      measurement of blood pressure in clinical, laboratory, and natural settings. The
      broad objectives of this report are to summarize the most critical methodological
      issues in the measurement of blood pressure and to present principles and
      recommendations for the evaluation of blood pressure methods and findings in
      published studies.

PMID- 8570791
TI  - ERP modulations indicate the selective processing of visual stimuli as a result
      of transient and sustained spatial attention.
AB  - Two experiments investigated selective processing as a result of transient and
      sustained visual-spatial attention. In Experiment 1, attention was cued on a
      trial-by-trial basis and event-related brain potentials were measured to stimuli
      preceded by valid, invalid, or neutral symbolic precues. Trial validity had only
      small effects on posterior P1 and N1 components. At midline electrodes, an
      enhanced negativity for valid as compared with invalid trials was present, which
      appeared to reflect initial processing costs for invalid trials followed by an
      additional processing benefit for valid trials. Experiment 2 investigated whether
      these effects are specific for transient spatial attention by comparing transient
      and sustained attention conditions. No indication of early processing costs was
      found in the latter case.

PMID- 8570792
TI  - Long-term extension to sleep--are we really chronically sleep deprived?
AB  - During 26 consecutive nights, electroencephalographic recordings and/or
      actigraphs were used to monitor the nighttime sleep of 10 asymptomatic healthy
      sleepers (mean age = 23.6 years). The schedule comprised: 7 nights of baseline
      sleep, 14 nights of extended sleep (up to 10 hr/night), and 5 nights of recovery
      sleep. During extended sleep, subjects slept significantly longer (approximately
      1 hr), but sleep latency and interim wakefulness deteriorated. Extended sleep
      produced no improvements to self-rated mood or subjective sleepiness. Vigilance
      tests showed a small but significant reduction in reaction time following
      extended compared with both baseline and recovery nights. Ability to detect
      target tones did not change significantly. Multiple Sleep Latency Test scores
      during extended sleep showed small (about 1 min) reductions. These findings give
      little support to the view of chronic sleep deprivation in the average 7.5-hr
      sleeper.

PMID- 8570793
TI  - Developmental and pharmacological analysis of the cardiac response to an acoustic
      startle stimulus.
AB  - The purpose of this research was to study the cardiac response of preweanling and
      adult rats to 10 presentations of an acoustic startle stimulus (0 ms rise time,
      100 ms, 130 dB, white noise stimulus). The first presentation of the startle
      stimulus produced a decrease in heart rate (HR) at both ages. With continued
      stimulus presentations, the response shifted to tachycardia in the adults but
      remained bradycardia in the preweanlings. Pharmacological analysis revealed that
      the startle stimulus activated only the parasympathetic system in the preweanling
      rats on all 10 trials. In contrast, the startle stimulus produced coactivation of
      the parasympathetic and sympathetic systems in the adults on the first trial,
      with the parasympathetic system predominating, and solely sympathetic activation
      on later trials. These results are discussed in terms of current
      psychophysiological models of (a) the cardiac response to startle stimuli and (b)
      autonomic space.

PMID- 8570794
TI  - Event-related brain potentials and error-related processing: an analysis of
      incorrect responses to go and no-go stimuli.
AB  - Recent research has suggested that there is a component of the event-related
      brain potential, the error-related negativity (ERN), that is associated with
      error detection and remedial actions such as error inhibition, immediate error
      correction, or error compensation. The present experiment used a go/no-go task to
      define more precisely the functional significance of this component. In this
      task, an ERN was observed for incorrect responses on go trials (errors of choice)
      and for responses on no-go trials (errors of action). Because errors of action
      cannot be corrected immediately by executing another response, these results
      indicate that the process manifested by the ERN is not dependent on immediate
      error correction. Other aspects of the data converge in suggesting that the ERN
      process is more closely related to error detection and that the connections
      between detection and remedial actions may depend on the task situation.

PMID- 8570795
TI  - Heart rate reactivity and heart period variability throughout the first year
      after heart transplantation.
AB  - Heart rate reactivity to mental stress is substantially blunted early after heart
      transplantation, suggesting that the loss of neural modulation limits the
      cardiovascular response to mental stress. We tested whether reactivity to mental
      stress recovers during the first year after heart transplantation. Hemodynamic
      and respiratory responses to mental arithmetic challenge were studied in 20 heart
      transplant recipients 3, 6, and 12 months after surgery. A normal comparison
      group was studied at equivalent intervals. Heart rate reactivity to mental
      arithmetic was significantly reduced in the cardiac transplant group compared to
      the normal subjects. This effect persisted up to 1 year after transplantation.
      Heart period variability in the heart transplant recipients was minimal in all
      three test sessions. The findings suggest that no functional reinnervation or
      other compensatory adaptation occurs up to 1 year after heart transplantation.

PMID- 8570796
TI  - Activation in novice and expert parachutists while jumping.
AB  - Heart and respiration rates were measured ambulatorily in 16 novice and 25 expert
      (> 380 delayed free-fall jumps) sports parachutists while making a static-line
      jump. Self-reported anxiety and heart rate peaked near the point of jumping in
      both groups rather than earlier in experts, as reported by Fenz and Epstein
      (1967, Psychosomatic Medicine, 29, 33-51). While sitting in the airplane 1 min
      before exit, mean heart rate was 124 bpm in novices and 102 in experts and
      increased during jumping to 170 and 145, respectively. The almost identical rise
      in the two groups could be accounted for largely by physical exertion, replicated
      with jumps from a training model on the ground. Exercise testing at a different
      location showed that experts were more fit. Respiration rate was higher in the
      airplane than at baselines, especially for novices. In conclusion, our results
      are more compatible theoretically with extinction of anticipatory anxiety than
      with learned anxiety inhibition.

PMID- 8570797
TI  - The effects of task type and task requirements on the dissociation of skin
      conductance responses and secondary task probe reaction time.
AB  - Although task-irrelevant events elicit smaller skin conductance responses (SCRs)
      than do task-relevant events, secondary task probe reaction time (RT) is often
      slower during the former. Three experiments (N = 48 in each) examined the effects
      of task demands, instructions, and stimulus discriminability on this dissociation
      effect. SCRs were larger to task-relevant stimuli in all experiments regardless
      of experimental manipulation. Subjects in Experiment 1 counted either all tones
      of one pitch (high/low group) or longer-than-usual tones of one pitch (longer
      group). There was more RT slowing during task-irrelevant tones at a 250-ms probe
      position in the high/low group and at a 150-ms probe position in the longer
      group. Experiment 2 employed differential Pavlovian conditioning in which the
      offset of task-relevant stimuli (CS+) coincided with the onset of a shock
      stimulus. Half the subjects were told which stimulus would be followed by shock
      (information group), whereas the others received no information (no-information
      group). Increased RT slowing during CS- was restricted to the no-information
      group. Experiment 3 employed visual conditioned stimuli that were easy or
      difficult to discriminate. RT slowing at 4,000 ms was greater during CS+, whereas
      there was a tendency for more RT slowing during CS- at 150 ms. There was no
      effect for CS discriminability. The results suggest that during both simple
      discrimination and during Pavlovian conditioning, task-irrelevant stimuli are
      more actively processed than task-relevant stimuli within the first 250 ms of
      stimulus presentation.

PMID- 8570798
TI  - Mental and physical countermeasures reduce the accuracy of the concealed
      knowledge test.
AB  - The effects of a physical (pressing the toes to the floor) and a mental (counting
      backward by sevens) countermeasure on the concealed knowledge test (CKT) were
      examined in a mock crime experiment with 40 subjects. Some knowledgeable subjects
      were informed about the nature of the CKT and were trained in the use of a
      countermeasure, whereas others remained uninformed. All subjects were offered a
      monetary reward if they could produce a truthful outcome. Subjects were tested
      using standard field techniques and instrumentation. The physical and, to a
      lesser extent, the mental countermeasures reduced the accuracy of the CKT. These
      results clearly demonstrate that the CKT has no special immunity to the effects
      of countermeasures.

PMID- 8570799
TI  - Timing and amplitude of saccades during predictive saccadic tracking in
      schizophrenia.
AB  - Schizophrenia patients have ocular motor abnormalities. It has been hypothesized
      that these abnormalities are associated with frontal eye field pathology. If so,
      schizophrenia patients should have difficulties decreasing saccadic reaction
      times in response to predictably moving targets. To evaluate the frontal eye
      field hypothesis, 25 schizophrenic and 26 nonpsychiatric subjects completed
      predictive saccadic tracking tasks. The groups demonstrated equivalent decreases
      in saccadic reaction times over consecutive trials. Schizophrenia patients,
      however, had faster reaction times and shorter amplitude saccades than
      nonpsychiatric subjects. The shorter amplitude saccades were made regardless of
      reaction time, perhaps an antipsychotic medication effect. The reaction time
      results are unlikely to be an effect of treatment with antipsychotic medication
      and are inconsistent with the hypothesis that schizophrenia patients have frontal
      eye field pathology.

PMID- 8570800
TI  - An audit of environmental health calls to a department of public health medicine.
AB  - PURPOSE: To audit telephone calls concerning general issues in communicable
      disease control and environmental health to a department of public health
      medicine. SETTING: A department of public health medicine in a district with a
      population of 190,000 during 1993. METHOD: A retrospective audit of forms
      designed to record all calls concerning environmental health and communicable
      disease control. The intervention was a change in design of forms and education
      of doctors dealing with the calls. A re-audit was done after these changes had
      been implemented. RESULTS: The number of recorded calls increased from 1.75
      (1992) to 3.29 (mid-1993) per week. Signing of forms increased from 61% to 83%
      and dating from 6% to 72%. All forms filled in by registrars or senior registrars
      were reviewed by the Consultant in Communicable Disease Control (CCDC). Very few
      calls were considered to be inappropriate. DISCUSSION: The increase in the number
      of calls was probably artefactual owing to better recording as a result of the
      audit. Improved recording will help in future training and audit, and be a medico
      legal safeguard.

PMID- 8570801
TI  - 'The planning compass': a tool for creative health promotion.

PMID- 8570802
TI  - The prevalence of behavioural problems amongst homeless primary school children
      in an outer London borough: a feasibility study.
AB  - OBJECTIVES: To investigate the prevalence of behavioural problems amongst
      homeless primary school-age children in an outer London borough. DESIGN: Cross
      sectional study of homeless primary school children and permanently housed
      control children. SETTING: Selected primary schools in an outer London borough.
      SUBJECTS: Children from non-refugee families officially accepted as homeless by
      the local authority, and housed controls from the same schools. OUTCOME MEASURE:
      Rutter behavioural rating scale. RESULTS: Fewer homeless children (38%, 18 of 48)
      than housed (88%, 50 of 57) were born in the UK, or spoke English at home. Only
      19 (40%) of the fathers of homeless children compared with 43 (75%) of housed
      children's fathers lived with them. Some 49% of homeless children's scores
      suggested a behavioural problem, compared with 11% of controls. Altogether, 94%
      of homeless and 100% of housed children were registered with a general
      practitioner. CONCLUSIONS: High levels of behavioural problems were found in
      homeless children. With numbers of homeless children expected to rise in the
      1990s this finding merits urgent attention.

PMID- 8570803
TI  - Health education campaign on population control: lessons from Iran.
AB  - A descriptive study was carried out in Tehran, the capital of Iran, to
      investigate a health education campaign on population control. A sample of 68
      adults aged 20 to 40 years participated in the study. Each respondent was shown a
      picture of the campaign. They then filled in a short questionnaire. The main
      objectives of the study were to measure recall rates and to assess attitude of
      the subjects. The study results show that recall rates were high (78%), 68% of
      respondents claimed that the campaign is likely to change their attitudes towards
      population control, and 87% of participants perceived the main idea of the
      campaign correctly. The study findings show that there are some significant
      associations between demographic variables (marital status, having child or not)
      and perception of the campaign. These may lead health educators and health
      promoters to communicate more effectively and efficiently in the context of
      family planning. In countries with a large number of young people, health
      education campaigns on population control with respect to social values of each
      society and moral considerations are recommended.

PMID- 8570804
TI  - Epidemiological transition in Latin America: the case of Chile.
AB  - To describe Chile's stage of epidemiological transition, a descriptive study of
      the changes to the demographic and economic profile of this country during the
      last 20 years is presented. The decline in the total fertility rate from 3.4 in
      1970 to 2.6 in 1992 and the important decrease in general and infant mortality
      rate has led to an increase of life expectancy of 8 years for men and 9 years for
      women. This has resulted in changes to the age structure and causes of mortality
      and morbidity of the population. A reduction of 82% in the proportion of deaths
      among children < 1 year and a 73% increase of mortality amongst those 65 years
      and older can be observed. In line with these changes non-communicable diseases
      have increased from 53.7% of all deaths in 1970 to 74.9% in 1991. In the same
      period mortality rates from cardiovascular causes have decreased from 189.6 to
      161.1 per 100,000 population, whilst their relative proportion of all causes has
      increased from 22.3% to 29%. High prevalence of risk factors should lead to a
      significant increase of chronic diseases in future years. Regarding morbidity, a
      high incidence rate for tuberculosis persists together with an increase of
      infections of the digestive system and of sexually transmitted diseases. A
      decrease in the rates of diseases preventable by immunisation has been noted. It
      is concluded that, as defined by population mortality statistics, Chile is in a
      post-transition stage but with a persistence of some infectious diseases
      corresponding to a transitional stage of development.

PMID- 8570806
TI  - Speech and language therapy: is it effective?: VAH Pearson, Public Health (1995);
      109: 143-153.

PMID- 8570805
TI  - Epidemiologic differences between candidial and trichomonal infections as
      detected in cytologic smears in Taiwan.
AB  - The epidemiologic differences between cytology-detected candidial and trichomonal
      infections were assessed in 15,933 women attending the 12 district health centres
      in the Taipei area and a consecutive 1114 patients, visiting venereal disease
      clinics, whose smears were screened for cervical cancer between July 1991 and
      December 1992 in Taipei. The Pap smears were examined for the presence of
      specific organisms, such as trichomonas vaginalis, vaginal candida, herpes
      simplex virus, human papillomavirus, actinomyces, leptothrix, aspergillu,
      gardnerella and others. More emphasis was placed on the candidial and trichomonal
      infection in inflammatory Pap smears. The overall prevalence of candidial and
      trichomonal infections was 3.40% and 1.88%, respectively. There were striking
      differences in the prevalence of trichomoniasis ranging from 1.74% in the
      district health centre population to 3.77% in the venereal disease clinic
      patients; however, the prevalence of candidial infection remained the same
      (3.40%) in these two distinct population groups. Indices of socioeconomic status-
      education and personal hygiene--showed an inverse association with the prevalence
      of trichomoniasis but a positive correlation with candidiasis. Among
      participants, younger age (< 20 years old) was independently associated with
      candidial (OR = 1.95) and trichomonal (OR = 3.87) infections. No sexual
      behavioural factors were associated with candidial infection in this study;
      however, having multiple sexual partners (OR = 5.07) was associated with a
      significantly elevated risk of trichomoniasis, while using condoms was associated
      with a diminished risk (OR = 0.38). The presence of candidiasis and
      trichomoniasis was highly associated with abnormal cytologic findings,
      particularly those indicative of inflammation. There was little evidence that
      findings suggestive of cervical cancer could be attributed to either candidial or
      trichomonal infections. These data suggest that trichomoniasis is consistent with
      venereal transmission of the disease, but transmission by contaminated objects
      cannot be ruled out because there is an increased relation between trichomoniasis
      infection and socioeconomic conditions and personal hygiene. Elucidation of such
      differences may be helpful in designing different strategies to control these
      infections. Furthermore, the findings can provide a good baseline of prevalence
      for investigating the relationship between these two pathogens and cervical
      dysplasia.

PMID- 8570807
TI  - A warning on gestational age at delivery.

PMID- 8570809
TI  - Global immunization of children on the rise, saving 3 million annually.

PMID- 8570808
TI  - OTA swan song has many verses.

PMID- 8570810
TI  - Radio is surprising key to reaching underserved.

PMID- 8570811
TI  - Clinical practice guidelines now on CD-ROM for libraries [new].

PMID- 8570812
TI  - W(h)ither public health?

PMID- 8570813
TI  - In search of the hypothesis.
AB  - Epidemiologic studies of racial differences sorely lack sound and explicit
      hypotheses. Race is a social convention, not a biological concept. Its careless
      use in epidemiology demonstrates a failure to generate appropriate hypotheses to
      study its role in health. Studies of hypertension in blacks illustrate the point.
      Two underlying pitfalls plague hypothesis generation: directionality involving
      the null and alternative hypotheses and circularity, where efforts to understand
      social factors have the effect of emphasizing racial differences. The proper
      prescription is to identify explicitly the hypotheses of interest, including
      their origins and implication.

PMID- 8570814
TI  - Beware of medical quick fixes.

PMID- 8570815
TI  - Another go at the experiment.
AB  - A number of states have experimented with legislation that would allow unlicensed
      international medical graduates to become physician assistants. These attempts
      have failed. The authors conducted a pilot evaluation study in California in
      response to legislative efforts. They examined the medical knowledge of a group
      of unlicensed international medical graduates and compared their clinical skills
      with those of a control group of recent graduates from a physician assistant
      training program. The unlicensed international medical graduates were below
      standard in medical knowledge and clinical skills and failed to make critical
      diagnoses in the tests with standardized patients. The authors conclude that
      unlicensed international medical graduates need additional training to be
      incorporated into the U.S. health care system as physician assistants.

PMID- 8570816
TI  - Patterns of decline among inpatient procedures.
AB  - This paper explores how the new financial incentives and organizational
      structures that prevail in the hospital industry have affected the mix of
      services provided by hospitals. Using data from the Agency for Health Care Policy
      and Research's Healthcare Cost and Utilization Project, the authors studied the
      150 procedures that were most frequently performed on inpatients in 1980. They
      found that (a) 37 of the 150 procedures declined in use more than 40 percent by
      1987, (b) patients that continued to receive one of the 37 procedures in 1987 on
      an inpatient basis tended to be more severely ill than in 1980, and (c) rates of
      decline were disproportionately large for Medicaid recipients. Three main factors
      have contributed to the decline in inpatient use of these procedures. Most
      important has been the shift from inpatient to outpatient settings, a result of
      new technologies and pressures from reimbursement mechanisms and utilization
      review policies. Some procedures have been replaced by less invasive, more
      effective approaches. Other procedures are now considered ineffective by the
      medical community and have been largely abandoned as a result.

PMID- 8570818
TI  - Lessons from the Georgia floods.
AB  - In July 1994, tropical storm Alberto brought heavy rains to parts of Alabama,
      Florida, and Georgia. In South Georgia, rivers rose 44 feet above flood stage,
      muddy water covered 10,000 square miles, and 31 lives were lost. In implementing
      the Health and Medical Services portion of the FEMA Federal Response Plan, the
      Public Health Service learned lessons from this experience that can be applied to
      planning for other natural disasters. Continuous reassessment to assure the best
      utilization of resources in rapidly changing conditions, cross-training in the
      content of emergency plans at all levels, and on-going face-to-face liaison among
      response managers will improve response efforts. Populations with special medical
      needs must become part of any response design. The effects that any response
      activity may have on the community as a whole should be carefully considered
      before action is taken.

PMID- 8570817
TI  - The next shift: managed care.

PMID- 8570820
TI  - Birth defects surveillance and the future of public health.

PMID- 8570821
TI  - Preventing deaths in Alaska's fishing industry.

PMID- 8570822
TI  - Evaluation of an Alaskan marine safety training program.
AB  - The Alaska Marine Safety Education Association provides commercial fishermen with
      an intensive 18-24-hour course addressing emergency preparedness, emergency
      response, and survival training. This study is a retrospective evaluation of the
      effectiveness of the course in reducing drownings and hypothermia deaths among
      commercial fishermen from January 1, 1991, to December 31, 1994. None of the 114
      fishermen who died during the study period were graduated from the course, and
      none of the 64 vessels on which a death occurred had an course-trained person on
      board.

PMID- 8570819
TI  - Surveillance for fetal alcohol syndrome in Colorado.
AB  - The authors performed surveillance for fetal alcohol syndrome with an existing
      birth defects registry. Fetal alcohol syndrome cases were identified from
      multiple sources using passive surveillance and from two selected medical sites
      using enhanced surveillance. Between May 1992 and March 1994, a total of 173
      cases were identified, and the medical records of the cases were reviewed to
      determine whether the cases met a surveillance case definition for fetal alcohol
      syndrome. Of these cases, 37 (21 percent) met either definite (28) or probable
      (9) criteria for fetal alcohol syndrome, 76 met possible criteria (44 percent),
      and 60 (35 percent) were defined as not fetal alcohol syndrome. Enhanced
      surveillance had the highest sensitivity for definite or probable cases, 31 of 37
      (84 percent), followed by hospital discharge data, 14 of 37 (38 percent). The
      authors also compared birth certificate information for 22 definite or probable
      cases in children born between 1989 and 1992 to birth certificate information for
      all Colorado births for that period. The proportion of mothers of children with
      fetal alcohol syndrome was statistically significantly greater (as determined by
      exact binomial 95 percent confidence limits) than the proportion of all mothers
      for the following characteristics: black race (0.23 versus 0.05), unmarried (0.55
      versus 0.22), not employed during pregnancy (0.86 versus 0.43), and started
      prenatal care in the third trimester (0.18 versus 0.04). Surveillance for fetal
      alcohol syndrome can be accomplished with an existing registry system in
      combination with additional case finding and verification activities. Through
      followup investigation of reported cases, data can be gathered on the mothers of
      children with fetal alcohol syndrome. These data could be used to target fetal
      alcohol syndrome prevention programs.

PMID- 8570823
TI  - False positive tuberculosis skin test results.
AB  - The re-emergence of tuberculosis as a significant public health threat has led to
      greatly renewed activity in tuberculin skin testing to identify infected persons.
      However, even use of the preferred skin test technique (intradermal injection of
      purified protein derivative via the Mantoux method) can lead to either false
      positive or false negative results. Interpretation of a Mantoux test can be
      influenced by cross reactions with other mycobacteria, intertester variation,
      host-response variation, and product related problems. At least 25 apparent false
      positive purified protein derivative skin test reactions in New York State in
      1992 appeared to be associated with lots of the derivative produced by one
      manufacturer. These unexpected skin test results led to examination of a product
      with an altered appearance that may have caused the unanticipated responses.
      After announcement of these false positive results to the press, the company
      removed the product from the market. Food and Drug Administration analysis later
      revealed particulate matter in vials of the suspected lots of purified protein
      derivative.

PMID- 8570824
TI  - Levels and predictors of HIV risk behavior among women in low-income public
      housing developments.
AB  - The prevalence of increases in human immunodeficiency virus infection and illness
      rates among urban disadvantaged women underscore the urgent need for acquired
      immunodeficiency syndrome prevention interventions for high-risk women. Few
      studies, however, have examined the factors contributing to risk in this
      population or predictors of risk taking and risk reduction. A total of 148 women,
      most of them of racial minorities, living in low-income public housing
      developments completed measures designed to assess risk for human
      immunodeficiency virus infection and to analyze factors related to risk taking,
      including knowledge about acquired immunodeficiency syndrome, behavior change
      self-efficacy, intention to use condoms, and social norm perception about safer
      sex practices. History of sexually transmitted diseases, low rates of condom use,
      and relationships with men who were injection drug users or who were not sexually
      exclusive were commonly reported. Women were divided into high- or low-risk
      categories based on behavior during the two preceding months. Women at low risk
      believed more strongly in personal efficacy of behavior change, were more
      committed to using condoms, and perceived risk reduction steps as more socially
      normative than high-risk women. Culturally tailored human immunodeficiency virus
      prevention interventions that address these dimensions are needed.

PMID- 8570825
TI  - Satisfaction of physician assistants and other nonphysician providers in a
      managed care setting.
AB  - Health maintenance organizations have employed physician assistants, nurse
      practitioners, and other nonphysician providers for decades, yet there is little
      information on how satisfied these providers are with this form of practice. This
      paper examines how physician assistants evaluate their experience practicing in a
      large group model health maintenance organization and compares their attitudes
      and satisfaction levels with those of other nonphysician providers-nurse
      practitioners, optometrists, mental health therapists, and chemical dependency
      counselors. The data source is a 1992 survey of 5,000 nonphysician employees of a
      health maintenance organization. The survey instrument was a self-administrated
      questionnaire that included both structured and open-ended questions. The
      response rate averaged 88 percent for physician assistants and the other non
      physician providers. Physician assistants expressed the most satisfaction with
      the amount of responsibility, support from coworkers, job security, working
      hours, supervision, and task variety. They were less satisfied with workload,
      control over the pace of work, and opportunities for advancement. Most physician
      assistants were also satisfied with pay and fringe benefits. Compared with other
      nonphysician providers, chemical dependency counselors expressed the highest
      levels of satisfaction across the various dimensions of work and optometrists the
      lowest. Nurse practitioners, chemical dependency counselors, and mental health
      professionals also tended to be satisfied with most aspects of practice in this
      setting. In a number of instances, they were more satisfied than the physician
      assistants. The findings are consistent with other studies that found health
      maintenance organizations to be favorable practice settings for physician
      assistants. The limits of physician assistant involvement and their role
      satisfaction and efficient use in HMOs are more likely to relate to physician
      attitudes and acceptance than to lack of support by coworkers and other
      attributes of the work environment.

PMID- 8570826
TI  - Is there any connection between a second pneumonia shot and hospitalization among
      Medicare beneficiaries?
AB  - To learn whether the risk of revaccination in adults should limit its use, the
      authors investigated whether adverse events requiring hospitalization occurred in
      a group of Medicare enrollees revaccinated with pneumococcal polysaccharide
      vaccine. A prospective cohort analysis and case study of revaccinated people
      involved five percent of all elderly Medicare enrollees from 1985 through 1988,
      consisting of 66,256 people receiving one dose of vaccine and 1,099 receiving two
      doses. Comparison was made of the hospitalization rate within 30 days after
      revaccination and rates of singly vaccinated persons using discharge diagnosis
      for all those hospitalized during the 30 days after revaccination. No significant
      difference was found between the hospitalization rate of the revaccinated cohort
      and comparison group. No adverse reactions attributable to pneumococcal
      polysaccharide vaccine causing hospitalization were identified among 39
      revaccinated persons who were hospitalized within 30 days of revaccination.
      Revaccination of elderly Medicare beneficiaries does not cause events serious
      enough to require hospitalization. Vaccination of persons according to the Public
      Health Service Immunization Practice Advisory Committee guidelines is recommended
      when the prior immunization status is unknown.

PMID- 8570827
TI  - Strategic questions for consumer-based health communications.
AB  - Using the consumer-oriented approach of social and commercial marketers, this
      article presents a process for crafting messages designed to improve people's
      health behaviors. The process, termed consumer-based health communications (CHC),
      transforms scientific recommendations into message strategies that are relevant
      to the consumer. The core of CHC is consumer research conducted to understand the
      consumer's reality, and thereby allowing six strategic questions to be answered.
      The immediate result of the CHC process is a strategy statement--a few pages that
      lay out who the target consumer is, what action should be taken, what to promise
      and how to make the promise credible, how and when to reach him or her, and what
      image to convey. The strategy statement then guides the execution of all
      communication efforts, be they public relations, mass media, direct marketing,
      media advocacy, or interpersonal influence. It identifies the most important
      "levers" for contact with the consumer. Everyone from creative specialists
      through management and program personnel can use the strategy statement as a
      touchstone to guide and judge the effectiveness of their efforts. The article
      provides a step by step illustration of the CHC process using the 5 A Day
      campaign as an example.

PMID- 8570828
TI  - Dimensions of homelessness.
AB  - Investigations of homelessness have been hampered by the lack of operational
      definitions sensitive enough to achieve subgroup differentiation and simple
      enough to permit replication. As a consequence, programming and policy
      development have often proceeded based on varying assessments of the composition,
      size, and needs of the homeless population. This paper describes the empirical
      use of duration of homelessness and dwelling place as elements of an operational
      definition of homelessness. The approach reflects a conceptualization of
      homelessness as a continuous variable that can be described by coordinates of
      time and place. A screening instrument that quantified the homeless experience
      was developed and evaluated in conjunction with a federally funded demonstration
      project for homeless substance-abusing men and women. Eight hundred and thirty
      nine men and women from six public detoxification centers were screened over a
      two-year period that began in August 1988. Respondents were asked eight questions
      to assess duration (time) and location (place) of homelessness before they
      entered the detoxification center. A simple index was constructed retrospectively
      and found to differentiate the sample into homeless and near-homeless subgroups.
      Between-group differences were statistically significant in demographics,
      presenting problems, and probability for successful intervention. These data
      paralleled previously reported differences between homeless subgroups and support
      the concurrent validity of the index. Cronbach's alpha (.72) showed the index to
      be moderately reliable. Differentiation of homeless persons into meaningful
      subgroups appears possible and programmatically recommended. Homelessness is not
      a unitary phenomenon, and it is unlikely to respond to therapeutic interventions
      that fail to consider individual differences.

PMID- 8570830
TI  - Consistency in self-reports of HIV testing: longitudinal findings from the
      National AIDS Behavioral Surveys.
AB  - This paper assesses consistency in self-reports of human immunodeficiency virus
      testing using two waves of longitudinal data from a large, national probability
      survey, the National AIDS Behavioral Survey. Of those reporting at Wave I that
      they had been tested for reasons other than blood donation, 18 percent reported
      at Wave 2 that they had never been tested. Of those reporting at Wave I that they
      had been tested when they donated blood, 29 percent reported at Wave 2 that they
      had never been tested. Inconsistent responses may be due to poor recall and to
      high self-presentation bias, that is, a desire to provide socially acceptable
      answers. Poor recall may be exacerbated by passive conditions such as blood
      donation. The authors conclude with recommendations for reducing measurement
      error in surveys of testing behavior.

PMID- 8570829
TI  - Prevalence of cardiovascular disease risk factors in a southwestern Native
      American tribe.
AB  - A cross-sectional study was conducted among the Pascua Yaqui Indian tribe in
      Tucson, AZ, in 1990 to document the prevalence of cardiovascular disease risk
      factors. Cardiovascular disease is the leading cause of mortality for Native
      Americans and for members of the Pascua Yaqui tribe specifically. A total of 230
      randomly selected adults, ages 25-65 years, who were listed as members on the
      tribal roll, participated, resulting in a 73-percent participation rate for those
      contacted. The five risk factors studied included diabetes, hypertension,
      hypercholesterolemia, obesity, and smoking. Only 14 percent of participants had
      none of the risk factors; 52 percent had two or more factors. Obesity was the
      most prevalent, being present in 69 percent of the women and 40 percent of the
      men, followed by diabetes, 35 percent of men and 39 percent of women. Twenty-six
      percent of the population had hypertension, and 43 percent of men were smokers,
      compared with 24 percent of women. Hypercholesterolemia was present in 19 percent
      of men and 14 percent of women. The rates of diabetes, obesity, hypertension, and
      smoking documented in this tribe are relatively high and can serve as a baseline
      for evaluating future prevention efforts.

PMID- 8570831
TI  - Youth beliefs and knowledge about the risks of drinking while pregnant.
AB  - Because no published studies of young persons' knowledge and awareness of fetal
      alcohol syndrome are available, the awareness and beliefs about drinking while
      pregnant in several large samples of young persons ages 13-20 are examined.
      Approximately 81 percent of the entire sample that completed questionnaires in
      school surveys believe that drinking alcohol while pregnant can definitely harm
      the fetus, although males and younger persons are less likely to believe in this
      risk. A substantial proportion of respondents believe that occasional heavy use
      is not harmful and suggest a safe level of drinking that is higher than the
      Surgeon General's abstinence recommendations. Only 72 percent have heard of fetal
      alcohol syndrome, and more than one-third incorrectly report that it describes a
      baby born addicted to alcohol, that the syndrome can be inherited, and that it
      can be cured. As in prior studies of adults, beliefs about drinking while
      pregnant are inconsistent with the Surgeon General's recommendations.
      Implications for increasing the awareness of the risk of drinking while pregnant
      are discussed.

PMID- 8570832
TI  - Ethnic disparity in the performance of prenatal nutrition risk assessment among
      Medicaid-eligible women.
AB  - In this study, the authors compare perinatal health outcomes and nutrition risk
      assessments in Latina, African American, and white women receiving Medicaid
      enhanced perinatal services. The objective is to analyze how proper assessment of
      obesity and underweight depend upon ethnic group, provider practice setting and
      credentials, and the implications for perinatal outcomes. The medical records of
      women who received enhanced perinatal services from specially certified Medicaid
      providers in California were abstracted for information on nutrition risk
      assessment and outcomes. Logistic regression analysis was used to test the
      associations first of obesity and underweight with adverse outcomes in Latina,
      African American and white women, then the associations of ethnicity with the
      failure of these women to be classified as overweight or underweight during
      assessment. Finally, the associations between misclassification of body mass with
      provider practice setting type and credentials are also tested. Obese Latinas are
      twice as likely not to be properly classified as overweight, despite evidence of
      substantial risk of unfavorable outcomes. For all three ethnic groups,
      underweight women are uniformly underreported as being at risk. The appropriate
      classifications of obesity and underweight are not associated with private or
      public types of obstetric practice settings or whether nutrition risk assessors
      are registered dietitians, health workers, or nurses of any particular
      credential. Providers of prenatal care to low-income women could improve the
      quality of nutrition risk assessment of overweight Latina women and underweight
      women of all ethnic groups with expectations of improving perinatal outcomes.

PMID- 8570833
TI  - The Public Health Service and the control of biologics.

PMID- 8570834
TI  - Making environmental data accessible for public health aims. The Massachusetts
      Environmental Database project.

PMID- 8570836
TI  - Arboreal clambering and the evolution of self-conception.
AB  - A fundamentally new psychology related to the ability to conceive of limited
      aspects of the self may have evolved in the ancestor of the great ape/human
      clade. Existing models of the evolution of primate intelligence do not provide an
      adequate explanation of the apparent restriction of this phenomenon. We propose
      that the capacity for self-conception evolved as a psychological mechanism
      enabling large-bodied, highly arboreal apes to cope with problems posed by the
      need to negotiate their way through a habitat that was fragile due to their body
      size. First, we briefly outline the case for believing that a new psychology
      related to self-conception evolved during the Miocene in the ancestor of the
      great ape/human clade. Next, we examine the existing models of the evolution of
      primate intelligence and assess their ability to account for the evolution of
      self-conception. Finally, we offer details of our alternative model, along with a
      series of predictions that can be derived from it.

PMID- 8570835
TI  - The False Claims Act. Litigating scientific misconduct.

PMID- 8570837
TI  - Rural vs. urban demand for medical imaging personnel.
AB  - Although there has been some anecdotal evidence regarding the demand for medical
      imaging personnel in the hospital setting, few statewide studies have documented
      the demand for such staff or compared data longitudinally. Using data from the
      North Carolina Council for Allied Health, the study reported in this article
      documented mean minimum hourly salaries and mean maximum hourly salaries, vacancy
      rates and time required to fill vacancies for nuclear medicine technologists,
      radiographers and ultrasonographers in rural and urban hospitals. Results
      indicated the vacancy rates were highest for ultrasonographers and lowest for
      radiographers. There were vacancy differences in rural compared to urban settings
      and for part-time compared to full-time employees.

PMID- 8570838
TI  - Informed patient consent: a historical perspective.
AB  - This article reviews the concept of informed patient consent by examining two
      long-term studies in which adequate consent was not obtained from study
      participants: the radiation experiments sponsored by the U.S. government
      beginning in the 1940s and the Tuskegee Syphilis Experiment conducted from 1932
      to 1972. The article discusses how these experiments represent a violation of
      informed consent guidelines and research ethics. It also explores the ethical
      implications of the experiments to radiologic technologists today and discusses
      the technologist's role in obtaining patient consent in research and clinical
      practice settings.

PMID- 8570839
TI  - Teleradiology: the practice of radiology enters Cyberspace.
AB  - Teleradiology refers to the use of computers and electronic communication
      networks to transmit diagnostic images acquired at one location to another
      location for review and interpretation. The use of teleradiology has grown
      tremendously during the past few years. Many of the early problems with
      teleradiology are being resolved by the rapid advances taking place in
      telecommunications and computer technologies, while changes in health care
      economics are driving the need to establish cost-effective and efficient
      communications links between rural and urban health care providers and tertiary
      care specialists. Effective arguments can be made both for and against the role
      of teleradiology in improving patient care. These arguments, as well as an
      overview of the impact of teleradiology on the the practice of radiology, are
      discussed in this article.

PMID- 8570840
TI  - The x-ray's link to brass music performance.

PMID- 8570841
TI  - Professional affiliations.

PMID- 8570843
TI  - The x-ray's early days.

PMID- 8570842
TI  - 1995 Glen W. Hartman Memorial Lecture. Leadership in radiology's second century.

PMID- 8570844
TI  - The case of the repetitious ripple.

PMID- 8570845
TI  - Stereotactic large core needle biopsy.

PMID- 8570846
TI  - Using case studies to teach radiography.

PMID- 8570847
TI  - Update on JRCERT educational standards.

PMID- 8570848
TI  - Magnetic resonance imaging of the breast.

PMID- 8570849
TI  - Take the next step in trend charts.

PMID- 8570850
TI  - Radiologic science education in Australia.

PMID- 8570851
TI  - The pedunculopontine tegmental nucleus: where the striatum meets the reticular
      formation.
AB  - The pedunculopontine tegmental nucleus (PPTg) contains a population of
      cholinergic neurons (the Ch5 group) and non-cholinergic neurons. There appears to
      be functional interdigitation between these two groups, which both have extensive
      projections. The principal ascending connections are with thalamic nuclei and
      structures associated with the striatum, including the substantial nigra pars
      compacta. The descending connections are with a variety of nuclei in the pons,
      medulla and spinal cord, concerned with autonomic and motor functions. In the
      past, emphasis has been laid on the role of the PPTg in locomotion and
      behavioural state control. In this review, we emphasise the role of the PPTg in
      processing outputs from the striatum. The non-cholinergic neurons receive outflow
      from both dorsal and vental striatum, and lesions of the PPTg disrupt behaviour
      associated with each of these. Our review indicates that the PPTg is less
      concerned with the induction of locomotion and more concerned with relating
      reinforcement (information about which comes from the ventral striatum) with
      motor output from the dorsal striatum. The conclusions we draw are: (1) the PPTg
      is an outflow system for the striatum, but also forms a 'subsidiary circuit',
      returning information to striatal circuitry; in this, the PPTg has an anatomical
      organisation that resembles that of the substantia nigra. (2) As well as a role
      in the mediation of REM sleep, cholinergic PPTg neurons have an important role in
      the waking state, providing feedback into the thalamus and striatum. (3) The
      precise function of the computations performed on striatal outflow by the PPTg is
      uncertain. We discuss whether this function is complementary (parallel to other
      routes of striatal outflow), integrative (modifying other forms of striatal
      outflow) or both.

PMID- 8570852
TI  - Regulatory role of ATP at developing neuromuscular junctions.
AB  - Neuronal factors co-released with neurotransmitters may play an important role in
      synaptic development and function. Extracellular application of adenosine 5'
      triphosphate (ATP), a substance co-stored and co-released with acetylcholine
      (ACh) in peripheral nervous systems, potentiated the spontaneous secretion of ACh
      at developing neuromuscular synapses in Xenopus 1-day-old cell cultures, as shown
      by a marked increase in the frequency of spontaneous synaptic currents recorded
      in the post-synaptic muscle cell. ATP also increased the frequency of miniature
      endplate potentials in the isolated tails of 2-week-old Xenopus tadpoles, with
      much smaller effect than that observed in cell cultures. The potentiation effect
      of ATP on ACh release in Xenopus cell cultures was inhibited by L-type Ca2+
      channel blockers, suggesting that the L-type Ca2+ channel is responsible for the
      positive regulation of spontaneous ACh secretion by ATP at the developing
      neuromuscular synapses. The frequency of spontaneous synaptic events was found to
      vary greatly from cell to cell in the culture, over two orders of magnitude.
      Synapses with high frequency events are probably under the influence of
      endogenously released ATP. In addition, ATP was shown to potentiate the responses
      of isolated myocytes to iontophoretically-applied ACh. Local application of ATP
      to one region of the elongated myocyte surface resulted in potentiated ACh
      responses only at the ATP-treated region. Single channel recording showed that
      ATP specifically increased the open time and opening frequency of embryonic-type,
      low conductance ACh channels. Pharmacological experiments suggest that ATP
      exerted both its pre- and post-synaptic effects by binding to P2-purinoceptors
      and activating protein kinase C. Moreover, the potentiation effects of ATP were
      restricted to the early stages of embryos. Taken together, these results suggest
      that ATP co-released with ACh or released from stimulated myocytes may promote
      synaptic development by potentiating pre-synaptic ACh release and post-synaptic
      ACh channel activity during the early phase of synaptogenesis.

PMID- 8570853
TI  - Geometry, kinetics and plasticity of release and clearance of ATP and
      noradrenaline as sympathetic cotransmitters: roles for the neurogenic
      contraction.
AB  - The paper compares the microphysiology of sympathetic neuromuscular transmission
      in three model preparations: the guinea-pig and mouse vas deferens and rat tail
      artery. The first section describes the quantal release of ATP and noradrenaline
      from individual sites. The data are proposed to support a string model in which:
      (i) most sites (> or = 99%) ignore the nerve impulse and a few (< or = 1%)
      release a single quantum of ATP and noradrenaline; (ii) the probability of
      monoquantal release is extremely non-uniform; (iii) high probability varicosities
      form 'active' strings; and (iv) an impulse train causes repeated quantal release
      from these sites. Analogy with molecular mechanisms regulating transmitter
      exocytosis in other systems is proposed to imply that coincidence of at least two
      factors at the active zone, Ca2+ and specific cytosolic protein(s), may be
      required to remove a 'fusion clamp', form a 'fusion complex' and trigger
      exocytosis of a sympathetic transmitter quantum, and that the availability of
      these proteins may regulate the release probability. The second section shows
      that clearance of noradrenaline in rat tail artery is basically > or = 30-fold
      slower than of co-released ATP, and that saturation of local reuptake and binding
      to local buffering sites maintain the noradrenaline concentration at the
      receptors, in spite of a profound decline in per pulse release during high
      frequency trains. The third section describes differences in the strategies by
      which mouse vas deferens and rat tail artery use ATP and noradrenaline to trigger
      and maintain the neurogenic contraction.

PMID- 8570854
TI  - Somatostatin and macrophage function: modulation of hydrogen peroxide, nitric
      oxide and tumor necrosis factor release.
AB  - Recent studies have shown that somatostatin modulates lymphocyte function, but
      the effects of somatostatin on macrophage function are not clearly defined. In
      the present study, peritoneal macrophages (Mluminal diameter) obtained from male
      rats were treated in vitro with somatostatin or octreotide and their effects on
      the release of hydrogen peroxide (H2O2), nitrite, and tumor necrosis factor (TNF)
      determined. Macrophages treated with somatostatin (10(-9) M to 10(-7) M) or
      octreotide (10(-8) M and 10(-7) M) released significantly greater amounts of PMA
      stimulated H2O2 than did the untreated controls. In addition, 10(-9) M of
      somatostatin significantly enhanced PMA-stimulated H2O2 release by LPS-treated
      Mluminal diameter. Octreotide had no effect on H2O2 release by LPS-treated
      Mluminal diameter. At concentrations of 10(-14) M, 10(-13) M, or greater than 10(
      8) M, somatostatin or octreotide suppressed nitrite release by Mluminal diameter.
      Somatostatin or octreotide did not affect nitrite release by LPS-treated Mluminal
      diameter. On the other hand, Mluminal diameter treated with 10(-11) M of
      somatostatin or octreotide released greater amounts of TNF than did the untreated
      controls. In contrast, TNF release by Mluminal diameter treated with 10(-9) M to
      10(-5) M of somatostatin or 10(-7) M to 10(-5) M of octreotide was less than that
      of the controls. Anti-TNF antibody (1:1000) caused a reduction in the release of
      H2O2 and nitrite. These findings demonstrate that somatostatin and octreotide
      modulate the release of H2O2, nitric oxide, and TNF by Mluminal diameter
      depending on the concentration of hormones used.

PMID- 8570855
TI  - Influence of place learning on somatostatin levels in the rat brain following
      environmental deprivation.
AB  - We have previously reported increased somatostatin levels in the cerebral cortex
      of rats housed in impoverished environment and subsequently subjected to a
      behavioural testing procedure, consisting of open-field exposure and spatial
      learning. The aim of the present study was to evaluate the degree of
      neurochemical specificity of the activation of somatostatin neurotransmission and
      to examine whether the altered levels were due to learning stimulation. Adult
      rats, previously housed individually for 30 days, were exposed to repeated
      sessions of a spatial learning task (2 days or 14 days) or repeated sessions of
      free swimming (14 days). The training sessions of the 14 day group consisted in
      recurrently changed position of the platform in a learning-set paradigm. Our data
      showed increased somatostatin immunoreactivity, and unchanged substance P
      immunoreactivity in the posterior part of the cerebral cortex. However,
      somatostatin levels increased to a similar extent following 14 days of repeated
      spatial learning sessions as free swimming sessions. We conclude that the
      activity of the cortical somatostatin system appears to be sensitive to
      environmentally induced sensorimotor stimulation in general, rather than learning
      per se. Thus, external stimulation of early clinical dementia patients with
      preserved sensorimotor receptivity, in an attempt to restore cognitive function,
      might be associated with altered somatostatin levels.

PMID- 8570856
TI  - The effects of intrathecal galanin message-associated peptide (GMAP) on the
      flexor reflex in rats.
AB  - We have examined the effects of intrathecal (i.t.) galanin message-associated
      peptide (GMAP), the C-terminal flanking peptide in the galanin (GAL) precursor
      protein, which is produced in equimolar quantities with galanin and which is
      upregulated upon axotomy, on the spinal nociceptive flexor reflex in decerebrate,
      spinalized, unanesthetized rats. I.t. GMAP elicited a moderate facilitation of
      the flexor reflex. No depression of baseline flexor reflex was observed with any
      dose of GMAP. The facilitation of the flexor reflex induced by conditioning
      stimulation (CS) of cutaneous C-afferents was dose-dependently blocked by GMAP.
      The reflex facilitatory effect of exogenously applied substance P (SP), one of
      the endogenous modulators of reflex hyperexicitability following C-fiber CS, was
      only blocked by GMAP at a relatively high dose. I.t. GMAP did not antagonize the
      reflex facilitatory effect of vasoactive intestinal peptide and did not
      potentiate the reflex depressive effect of i.t. morphine or clonidine. Finally, 1
      micrograms i.t. GMAP did not influence spinal cord blood flow whereas 10
      micrograms GMAP induced a transient decrease in spinal cord blood flow in some
      experiments. The ability of GMAP to block the increase in spinal cord
      excitability following repetitive C-fiber stimulation may be through a
      presynaptic action. Although some of the effects of GMAP were similar to galanin,
      distinct differences were found, particularly in interaction with other
      excitatory and inhibitory agents. It is possible that GMAP exerts its action in
      the spinal cord through its own specific receptor. GMAP may act similarly to GAL
      in some, but not all pharmacological functions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570857
TI  - Neuropeptide immunoreactivity and co-existence in cardiovascular nerves and
      autonomic ganglia of the estuarine crocodile, Crocodylus porosus, and
      cardiovascular effects of neuropeptides.
AB  - The two aortas of the crocodile are in open connection at two sites, the foramen
      of Panizzae immediately outside the ventricles, and the arterial anastomosis at
      the level of the gut. The present study was performed to elucidate the
      innervation of the cardiovascular structures of the crocodile, in part to provide
      a further basis for the assumption that the apertures of the foramen and the
      anastomosis may be altered, possibly leading to changes in the flow profiles of
      the central vessels. The presence of smooth muscle arranged at the circumference
      of the foramen and in the walls of the anastomosis was demonstrated. The
      cardiovascular structures were innervated by nerves containing co-existing
      tyrosine hydroxylase, NPY and somatostatin immunoreactivities, which also
      occurred in neurons of the sympathetic ganglia. CGRP and substance P
      immunoreactive material co-existed in cardiovascular nerves, and in the nodose
      ganglion. In addition, bombesin, VIP and galanin immunoreactive nerves were
      found. Effects of neuropeptides on blood flows and blood pressures were studied
      in vivo. Substance P increased all blood flows measured, NPY increased the flow
      through the arterial anastomosis while neurotensin caused an initial decrease in
      the flow through the arterial anastomosis. In conclusion, there is a rich
      innervation of the heart and major vessels of the estuarine crocodile, including
      the foramen of Panizza and the arterial anastomosis. These nerves possibly
      regulate the distribution of blood in the cardiovascular system, which is further
      suggested by the results of the injection of neuropeptides.

PMID- 8570858
TI  - Differential effects of deltorphin on arginine and galanin-induced growth hormone
      secretion in healthy man.
AB  - Recently we demonstrated the inhibitory action on Growth Hormone (GH) secretion
      of an opioid heptapeptide, deltorphin (DT), that is highly selective in binding
      delta-opioid receptors. To investigate the possible mechanism leading to the
      decrease in GH secretion by specific activation of delta-opioidergic pathway in
      man, we compared, in normal subjects, the effect of DT on GH secretion responses
      to two different GH secretagogues, namely arginine (ARG) and galanin (GAL). DT
      completely blunted the GH response to ARG, whereas it attenuated the GH response
      to GAL, but not at a statistically significant level. We suggest that the
      specific activation of delta-opioid receptors in man may exert an inhibitory
      influence on GH secretion principally by modulating endogenous hypothalamic
      somatostatin (SRIH) release.

PMID- 8570859
TI  - Mobilization of gastric histamine during repeated administration of a proton
      potassium adenosine triphosphatase inhibitor in intact and antrectomized rats.
AB  - Intact and antrectomized female rats were treated with the potent proton pump
      inhibitor, E3810 (daily 40 mg/kg weight, s.c.) for 4 weeks. Plasma gastrin
      concentration and urinary excretion of N-terminal big gastrin increased until day
      14 and persisted at a high level in intact rats treated with E3810, but did not
      increase in antrectomized rats. Urinary excretion of histamine increased
      progressively and reached 7 times the control value following 4 weeks of
      treatment with E3810 in intact rats, but not in antrectomized rats. At the
      termination of the treatment, the endocrine cell density in the oxyntic mucosa of
      intact rats had increased by 85% with increased histamine content and elevated
      histidine decarboxylase activity, while antrectomized rats showed a low histamine
      level and low histidine decarboxylase activity. Administration of gastrin-17 I
      (10 micrograms/kg weight, sc) itself caused a significant increase in urinary
      excretion of histamine, which was inhibited by the specific gastrin receptor
      antagonist, L-365,260. These results suggests that the massive urinary excretion
      of histamine caused by the treatment with E3810 reflects gastrin-induced
      mobilization of gastric histamine and that neither E3810 itself nor E3810-induced
      luminal pH elevation has direct effects on mobilization of oxyntic mucosal
      histamine.

PMID- 8570861
TI  - Cadmium-associated renal disease.
AB  - Cadmium is widely used in industry, causing exposure of workers and environmental
      pollution because of its persistence in the biosystems. Its very long half-life
      in the human organism causes its accumulation over the lifetime in liver and
      kidneys. Cadmium ions have a high affinity for tissue thiols, induce the
      synthesis of a carrier cysteine-rich polypeptide called metallothionein, and
      impair proteoglycan metabolism. Significant renal effects include tubular
      nephropathy manifested by proteinuria, amino aciduria, glucosuria, phosphaturia,
      and calcium wastage. Chronic sequels include decrease in the glomerular
      filtration rate and increased risk of kidney stone disease. Biological monitoring
      of cadmium absorption includes determination of urinary cadmium and of low
      molecular weight marker proteins, such as beta2-microglobulin or retinol binding
      protein, the tubular reabsorption of which is impaired before a frank
      proteinuria.

PMID- 8570860
TI  - Divergent mechanisms of insulin-like growth factor I and II on rat hepatocyte
      proliferation.
AB  - Insulin-like growth factors I and II are peptides with a structural homology for
      proinsulin, and are involved in hepatocyte proliferation. IGF-I and IGF-II,
      however, have different metabolic roles, and their mechanisms of action are
      incompletely known. We hypothesized that IGF-I and IGF-II act by different signal
      transduction pathways. To test this hypothesis, hepatocytes from 200 g male
      Sprague-Dawley rats were isolated by a two-step collagenase perfusion technique
      and plated at a density of 10(5) cells/16 mm Primaria plate. Proliferation was
      measured by [3H]thymidine ([3H]thy) incorporation into DNA, and an
      autoradiographic nuclear labeling index (LI). To analyze signal transduction,
      cyclic AMP (cAMP) levels were measured 5 min after addition of reagents by a
      radioimmunoassay. Reagents (doses) used were: IGF-I (2 nM), IGF-II (2 nM), the
      inhibitory peptide somatostatin-14 (SS14) (10 nM), and the adenylyl cyclase
      antagonist dideoxyadenosine (DDA) (10 microM). A summary of the findings is as
      follows: (1) IGF-I stimulates [3H]thy, LI and cAMP accumulation. (2) IGF-II
      stimulates [3H]thy and LI but not cAMP; (3) IGF-I but not IGF-II effects are
      inhibited by SS14 and DDA. We conclude that the hepatotrophic effects of IGF-I
      and IGF-II occur by different mechanisms: IGF-I is cAMP-dependent, IGF-II is cAMP
      independent.

PMID- 8570862
TI  - Real-time monitoring of renal function during ischemic injury in the rhesus
      monkey.
AB  - The presence of delayed graft function (DGF) following cadaver donor renal
      transplantation is associated with inferior graft survival as well as decreased
      patient survival. Delay in onset of function eliminates a valuable indicator of
      allograft viability, which is not easily replaced by standard diagnostic
      procedures. The purpose of this study was to demonstrate that a new clearance
      technique could be used to measure renal function minute to minute and under
      conditions similar to those observed in humans in the immediate
      posttransplantation period. A monkey model was used to provide controlled
      conditions. Increasing levels of ischemic injury were produced in 12 Rhesus
      monkeys by renal hilum cross-clamping. Real-time measurements of glomerular
      filtration rate (GFR) were obtained from the rate of clearance of the
      extracellular fluid of the GFR agent 99mTc-DTPA, as measured with a specially
      designed external radioactivity counting device called the ambulatory renal
      monitor, or ARM. GRF was measured every 2-5 min as the slope (k) of the log of
      activity measured minute to minute versus time. GFR measurements were correlated
      with blood urea nitrogen (BUN), plasma creatinine (Cr), routine light microscopy,
      and measurement of proliferating cell nuclear antigen (PCNA), a marker of cell
      proliferation. Large changes in renal function due to ischemia or ureteral
      obstruction were observed within minutes. In addition, the rate constant on Day 1
      was predictive of peak serum Cr(R =--0.86, R2=.74, p = .0001). Acute tubular
      necrosis (ATN) resolution was reflected more quickly when using the rate constant
      (Day 1) than when using either BUN or plasma Cr (Day 3-4). Because of renal
      functional reserve, BUN and plasma Cr were relatively insensitive indicators of
      mild to moderate reductions in GFR as compared with the rate constant. We
      conclude that ARM is a simple method which provide an accurate, near real-time
      GFR readout with potential applications not only for the clinical management of
      patients with DGF, but also as a research tool in acute renal failure (ARF).

PMID- 8570863
TI  - Induced alterations in calcium uptake rate in normoxic rate proximal tubules.
AB  - This study is well-oxygenated, freshly isolated rat proximal tubules (RPT),
      examined the effects of several drugs that alter the transmembrane K+ and Na+
      gradients across cell membranes, including valinomycin (VAL), amphotericin B
      (AMPHO), and ouabain (OUAB). The effects of high extracellular potassium chloride
      (KCl) concentrations (45 mM) and low extracellular sodium concentration (100mM)
      were also studied. After 10 min of drug exposure Ca2+ uptake rate (nmol/mg/min)
      increased from 2.7 to 3.8 with VAL (p < .02), from 2.9 to 3.7 with AMPHO (p <
      .05), from 3.6 to 4.1 with OUAB (p < .05), and from 3.2 to 4.8 with 45 mM KCl (p
      < .001). Ca2+ uptake rate was sustained at these high levels at 20 min in all
      treated RPT except those exposed to OUAB. LDH release averaged less than 15% in
      control tubules and did not increase significantly except in RPT treated with
      VAL, where LDH release at 10 min was 48% and at 20 min was 57% (both p < .001).
      Of importance, only in VAL-treated RPT did ATP decrease to low levels (6.7
      nmol/mg in control to 2.0 +/- 0.3 nmol/mg in VAL, p < .001). Treatment with
      verapamil reduced Ca2+ uptake rates at 10 min in VAL-treated RPT (from 3.8 to
      3.1, p < .02, in AMPHO-treated RPT (from 3.8 to 3.1 p < .001), in OUAB-treated
      tubules (from 4.0 to 3.4, p < .01), and in KCl-treated RPT (from 3.7 to 3.2, p <
      .01). These results indicate that acute changes in the transmembrane ion gradient
      in RPT are accompanied by increased Ca2+ uptake rates. Ca2+ uptake rates are also
      increased during O2 deprivation in RPT, a situation in which the transmembrane
      ion gradient is likewise altered. The increased Ca2+ uptake rate observed in the
      present study and during hypoxia may have a common basis, that is, altered
      transmembrane ion gradients or some function thereof.

PMID- 8570864
TI  - Mechanism of sex-related differences in nephrotoxicity of 1.2-dichloropropane in
      rats.
AB  - The contribution of testosterone to the nephrotoxic effects of 1,2
      dichloropropane (DCP) was assessed by a series of castration and sex hormone
      replacement experiments on Wistar rats. The nephrotoxic action of DCP was
      evaluated by measuring the accumulation of organic anion and release of aspartate
      aminotransferase into the incubation medium using a renal cortical slice model.
      Our data show that sex, castration, and testosterone pretreatment are factors
      that influence the effect of DCP on renal cortical slices of rats Males appear to
      be more sensitive to nephrotoxic effects of DCP than females, male castration
      prevents the nephrotoxic effects of DCP, and pretreatment of females and
      castrated males with testosterone increases the susceptibility to DCP. In this
      study an attempt was made to evaluate the role of sex differences in the
      expression of enzymes participating in Phase I and Phase II detoxication
      reactions in order to explain the differences in sensitivity of the two genders
      to the nephrotoxic action of DCP. Our results implicate gender-specific
      expression of cytochrome P-450 in the kidneys as a predominant factor that
      determines the different susceptibilities of male and female rats to the
      nephrotoxic effect of DCP. We propose that the oxidation of DCP by CYP IIE1 is
      the first saturable and limiting step in the metabolic activation of DCP to
      nephrotoxic metabolites. It appears that, despite the fact that the nephrotoxic
      effect of DCP is determined mainly by its cysteine-conjugated metabolites,
      gluthathione (GSH) content and glutathione S-transferase (GST) activity in kidney
      are not directly related to increased androgen-related susceptibility to
      DCP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570865
TI  - Protective effect of coconut oil on renal necrosis occurring in rats fed a methyl
      deficient diet.
AB  - Weanling rats fed a methyl-deficient diet develop renal necrosis with acute renal
      failure. The aim of this experiment was to explore further the role of coconut
      oil in this experimental model. Weanling Wistar male rats were fed methyl
      deficient and their controls were fed methyl-supplemented diets. Coconut oil was
      fed at 14% and 20%, the latter concentration with and without 1% safflower oil
      (rich in linoleic acid); other groups received similar diets but instead of
      coconut oil, a mixture of hydrogenated vegetable oil and corn oil (rich in
      unsaturated fatty acids) was employed. Coconut oil fed at a 14% concentration did
      not evidence any protective outcome in relation to the renal lesions. Coconut oil
      at a 20% concentration showed a protective effect, mainly when the diet included
      safflower oil. The renal protective effect was evidenced by less or no mortality
      and increased survival time in the methyl-deficient rats receiving coconut oil,
      as well as by a reduced incidence (%) and severity of the renal lesions as
      evaluated by renal weight, and type (tubular and cortical necrosis or repair) and
      extent (grade) of the renal damage. The lack of a protective outcome when coconut
      oil was fed at 14%, along with the fact that in those rats receiving coconut oil
      at 20% the protection was greater when the diet was supplemented with 1%
      safflower oil, indicates that the protective effect should be attributed to the
      type of fatty acids coconut oil has and not to their shortage of essential fatty
      acids.

PMID- 8570866
TI  - Protective effect of N-benzyl-D-glucamine dithiocarbamate against renal toxicity
      in rats during repeated cis-diamminedichloroplatinum administrations.
AB  - The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) against the
      renal toxicity caused by repeated injections of cis-diamminedichloroplatinum
      (DDP) were studied in rats. The rats were injected i.p. with BGD (2.0 mmol/kg)
      immediately after i.v. injection of DDP (20 mumol/kg), and after 10 and 20 days
      they received repeated treatments with the same doses of DDP and BGD. Treatment
      with BGD prevented nephrotoxicity after repeated DDP administrations. Repeated
      DDP injections increased lipid peroxidation in the kidney and decreased GSH
      concentration in the kidney at 5 days after the third injection of DDP. BGD
      treatment prevented the increase in lipid peroxidation and the decrease in the
      GSH concentration caused by repeated administration of DDP. The determination of
      activities of antioxidant enzymes in the kidney showed that catalase activity
      decreased after repeated DDP administrations and that superoxide dismutase
      activity tended to decrease. Changes in activities of these enzymes were
      prevented by BGD treatment. The platinum concentrations in kidney and liver were
      decreased by BGD treatment. These results indicate that BGD treatment prevents
      the accumulation of platinum in the kidney after repeated administrations of DDP,
      resulting in protection against the DDP-induced renal toxicity.

PMID- 8570867
TI  - Concentrating capacity in ifosfamide-induced severe renal dysfunction.
AB  - BACKGROUND: Diabetes insipidus renalis has only occasionally been reported in
      ifosfamide-induced renal Fanconi's syndrome, but in two studies on subclinical
      renal impairment, low morning urine osmolarity was found in high frequencies.
      This study was performed to assess the frequency of defective concentrating
      capacity in patients with ifosfamide-induced renal Fanconi's syndrome or severe
      impairment of proximal tubular function. PATIENTS AND METHODS: Seven patients
      with overt Fanconi's syndrome and 5 with a generalized but subclinical
      tubulopathy were examined. Beside proximal tubular solute reabsorption and
      estimation of glomerular filtration rate, urinary osmolarity was measured after
      overnight fast and DDAVP (1-D-amino-8-D-arginine vasopressin) testing. RESULTS:
      Five out of 7 patients with overt Fanconi's syndrome, but no patient with only
      subclinical tubular damage, had decreased osmolarities by at least one test.
      Increased sodium excretion was additionally found in 4 of these patients.
      CONCLUSION: Impaired renal concentrating capacity is a rare event in ifosfamide
      induced renal dysfunction and confined to patients with overt Fanconi's syndrome.
      These patients should, however, undergo evaluation of concentrating capacity and
      renal sodium handling as decreased concentrating capacity and increased sodium
      excretion would render a patient at risk for dehydration episodes.

PMID- 8570868
TI  - Endothelin in patients with chronic renal failure.
AB  - Hypertension, anemia, and arteriovenous shunts represent very important
      pathogenic factors in the occurrence of cardiovascular morbidity and mortality in
      patients with chronic renal failure. It can be expected that endothelin (ET), the
      most potent vasoconstrictor known at present, can react in a significant way to
      the hemodynamic changes caused by the construction of a vascular shunt or anemia.
      In 14 patients the plasma ET concentration was examined before and 24 and 7 days
      after the construction of arteriovenous fistula. In 27 patients undergoing
      chronic hemodialysis treatment, ET was examined before the erythropoietin (EPO)
      therapy and after 2 months of EPO therapy, when partial correction of anemia had
      been achieved. The construction of arteriovenous fistula by itself had no
      significant influence on the plasma ET concentration. Subcutaneous application of
      EPO in doses that led to gradual correction of anemia was not accompanied by the
      rise of plasma ET. The average plasma concentration of ET was significantly
      higher in hemodialyzed patients, when compared to healthy controls as well as to
      patients with chronic renal failure before hemodialysis treatment was started.

PMID- 8570869
TI  - HCV viremia in hemodialysis patients: detection by a DNA enzyme immunoassay for
      amplified HCV sequences.
AB  - The aim of this study was the detection of HCV viremia in both anti-HCV antibody
      positive and negative hemodialysis patients. Sera from 75 patients on
      extracorporeal blood purification in the same dialysis unit were analyzed. Anti
      HCV antibodies were detected using a 2nd-generation ELISA assay and in all
      positive cases a RIBA 3rd-generation test was performed. HCV-RNA was tested by a
      reverse transcription-nested polymerase chain reaction (RT-PCR) assay with
      primers located in the 5' region. PCR products were analyzed by a nonradioactive
      hybridation assay. The presence of anti-HCV antibodies was detected in 30 (40%)
      patients by means of ELISA II test; 28 of them were RIBA III positive and two
      indeterminate. Twenty-four of the 30 HCV Ab ELISA II positive patients (80%) were
      HCV-RNA positive (23 RIBA III positive and 1 indeterminate). Six anti-HCV Ab
      ELISA II positive patients tested negative for HCV-RNA (20%); 5 of these patients
      were also positive for anti-HCV antibodies with a RIBA III test and 1 was
      indeterminate. None of the anti-HCV negative patients was HCR-RNA positive. In
      two cases we documented the disappearance of viremia after an acute HCV
      infection, with the persistence of antibody reactivity. In conclusion, anti-HCV
      antibody positive hemodialysis patients should be considered as potentially
      infectious.

PMID- 8570870
TI  - CAPD adequacy and dialysis morbidity: detrimental effect of a high peritoneal
      equilibration rate.
AB  - Conventional urea kinetic modeling and peritoneal equilibration test (PET) were
      performed on 73 patients undergoing CAPD in order to determine factors
      influencing morbidity. Dialysis adequacy (KT/V, creatinine clearance, efficacy
      number) and nutrition (PCR, nPCR, creatinine generation rate, body mass index,
      albumin, transferrin) were compared to hospital admission days, blood pressure
      medication, and semiquantitative symptom indices. Renal clearance and dialysis
      intensity were the primary determinants of dialysis adequacy: patients without
      renal function required a dialysis intensity of > 0.15 L/kg/day for adequate
      dialysis, while patients with a renal clearance > 2 mL/min only required 0.1
      L/kg/day. Ultrafiltration and PET played a minor role. High peritoneal
      equilibration rates (PER) were associated with increasing height, chronic
      glomerulonephritis, and recent peritonitis; low PER with polycystic renal disease
      and long CAPD duration (for patients without recent peritonitis). There were
      significant positive correlations between dialysis adequacy indices and
      nutritional indices: nPCR (p < 0.001); creatinine generation rate (p < 0.001),
      albumin (p < 0.01), and negative correlations to symptom indices: fatigue (p <
      0.01), nausea (p < 0.05), pain (p < 0.05), and symptom index (p < 0.01).
      Nutritional indices correlated negatively to morbidity indices: 1-year admission
      rate (p < 0.01), pain (p < 0.01), itching (p < 0.05), edema (p < 0.05). A high
      PER was a powerful and independent predictor of clinical morbidity:fatigue (p <
      0.01), nausea (p < 0.01), pain (p < 0.01), edema (p < 0.05), symptom index (p <
      0.001), blood pressure medication (p < 0.01), and 1-year admission rate (p <
      0.01). CONCLUSION: Adequate dialysis is difficult to obtain in CAPD patients with
      no renal function, and malnutrition is therefore common. Morbidity improves with
      increasing nutrition and dialysis intensity, there being no apparent plateau.
      Creatinine clearance and serum albumin are the most useful indices. A high PER
      paradoxically predicts a poor clinical outcome, due to increased loss of protein
      in the dialysate, poor ultrafiltration, and appetite suppression secondary to
      increased glucose absorption. Patients with a high PER should preferably be
      treated with nightly peritoneal dialysis or hemodialysis.

PMID- 8570871
TI  - Renal hemodynamic response to the creation of vascular access in patients with
      end-stage renal disease.
AB  - To evaluate the possibility that the placement of arteriovenous anastomosis (a/v
      a) may lead to the attenuation of glomerular hyperfiltration, we studied 5
      nondiabetic patients before and after creation of vascular access for
      hemodialysis. Patients received no EPO and antihypertensive therapy was
      discontinued 24 h before each study. Cardiac output (CO) and a/v a flow rates
      were measured by Doppler echo, and GFR and ERPF by plasma decay curves of Tc99m
      DTPA and 131I-hippuran, respectively. Other parameters were calculated by
      standard formulas. Augmentation of CO and decrease in systemic vascular
      resistance occurred in all patients (p = 0.05), yet renal findings were less
      predictable since only three patients showed a decrease in renal vascular
      resistance and filtration fraction post a/v a. Thus, there is a discordant
      pattern of renal hemodynamic response to the creation of a/v a in end-stage renal
      disease and further studies are needed to better define the subset of patients
      who are prone to renal vasodilation after the placement of a/v a.

PMID- 8570872
TI  - Crescentic glomerulonephritis as renal cause of acute renal failure.
AB  - Over a period of 5 years, we observed 28 patients with biopsy-proven crescentic
      glomerulonephritis. Four of these patients were ANCA associated (pauci immune), 1
      had anti-glomerular basement membrane antibodies (anti-GBM), and the other 23
      cases had immune complex form (22 poststreptococcal and 1 poststaphylococcal).
      Acute renal failure as a main clinical feature was found in 11/28 (35.7%), all
      with more than 80% crescents, including all ANCA-associated cases, anti-GBM form,
      and the patient with poststaphylococcal form. Using "pulse" therapy with
      methylprednisolone, cyclophosphamide, and plasmapheresis, renal function was
      improved in 5/11 (45.4%), diuresis started, and end-stage renal disease was
      delayed. The therapy was continued orally with steroids and cyclophosphamide. The
      second attach of oligoanuria developed after a period of 6-12 months without
      improvement after the therapy used previously (during the first attack), and it
      was necessary to begin chronic hemodialysis treatment.

PMID- 8570873
TI  - Abortion prohibition and acute renal failure: the tragic Romanian experience.
AB  - During the period 1966-1989, pregnancy interruption was severely punished in
      Romania. However, natality rose only temporarily, while illegal abortions reached
      at least 3.36%/year and became the main etiology of ARF. From the 653 patients
      hemodialyzed for ARF during 1979-1989 in Cluj, 131 (20.07%) had abortions; during
      1990-1993 only 3 (1.52%) had this diagnosis. Of the women with postabortion ARF,
      71.64% were oligoanuric. The average duration of oligoanuria was 18.9 days, the
      longest reversible oligoanuria 89 days, the mean schedule of dialysis 1/2.98
      days. Hysterectomy was performed in 44.3%; chronic renal failure occurred in
      8.21% of the patients. Mortality rate averaged 14.92%, being greater in
      hysterectomized women (18.64%) and in those with a BUN over 150 mg% at admission.
      The survivors had to face the menace of imprisonment and the interrogation of
      prosecutors already in the hospital, regardless of their health problems.

PMID- 8570874
TI  - Unsuccessful treatment of CAPD peritonitis caused by Alcaligenes xylosoxidans
      subsp. denitrificans.

PMID- 8570875
TI  - Fulminating systemic capillary leak syndrome with lymphocytosis and
      hypogammaglobulinemia.
AB  - We report a case of fulminating systemic capillary leak syndrome which
      temporarily responded to verapamil, a calcium channel blocker. We noted two
      features of the disease not previously reported: a rise in lymphocyte count 2-3
      days prior to an attack, and hypogammaglobulinemia. These findings are discussed
      in relation to the possible etiology of this disease.

PMID- 8570876
TI  - Systemic mucormycosis complicating acute renal failure: case report and review of
      the literature.
AB  - Mucormycoses is a fungus which increasingly has been reported as a cause of
      opportunistic infection during the last 40 years. This infection is most commonly
      associated with underlying predisposing conditions, particularly diabetic
      ketoacidosis, hematologic and other malignancies, steroid therapy, broad-spectrum
      antibiotic therapy, or various acquired and hereditary immunodeficient disease
      states. The present report is that of a previously healthy patient with acute
      renal failure secondary to a postviral rhabdomyolysis syndrome, who received
      corticosteroids and developed unsuspected and undiagnosed systemic mucormycosis.
      Autopsy revealed that he died as a consequence of a massive pulmonary hemorrhage
      due to disseminated invasive mucormycosis, involving both the lungs and kidneys.
      A review of the literature reporting disseminated mucormycosis in association
      with renal failure is provided. Mucormycosis should be considered in
      immunocompromised patients with renal failure and fevers of unknown origin so
      that early diagnosis and prompt surgical and medical therapy may be instituted.

PMID- 8570877
TI  - The impact of long-term hemodialysis on pituitary-adrenocortical function.
AB  - The activity of the hypothalamic-pituitary-adrenal axis in hemodialyzed (HD)
      patients has been investigated, with conflicting results. Different results are
      reported concerning both basal ACTH and cortisol concentration and the responses
      to different stimulating agents, in chronic hemodialyzed patients. The present
      study was performed in order to asses whether the length of the hemodialytic
      treatment may affect the pituitary and adrenocortical response to stimulation
      with ovine CRH (oCRH) and with exogenous ACTH in a group of patients on chronic
      HD for more than 10 years. Ten uremic patients (aged 38-71, 6 males and 4
      females) on chronic hemodialysis for at least 10 years and 7 healthy subjects
      matched for age and sex were studied. The patients were tested on the day
      preceding dialysis session. Each subject received on different non-consecutive
      days oCRH (100 micrograms i.v. in bolus) and ACTH (Synacthen 0.25 mg i.v. in
      bolus), and blood samples were obtained at appropriate intervals. Basal ACTH and
      cortisol levels of HD patients were in the upper limit of normal range (ACTH
      39.21 +/- 11.11 pg/mL in HD patients vs. 26.88 +/- 14.12 pg/mL in controls;
      cortisol 19.96 +/- 5.07 in HD patients vs. 12.66 +/- 4.44 in controls); however,
      the means were not significantly different compared with controls. Following oCRH
      administration a net increase of ACTH and cortisol was observed in every patient
      tested (ACTH peak 83.81 +/- 28.49 in HD vs. 78.73 +/- 22.87 pg/mL in controls;
      cortisol peak 30.73 +/- 19.31 in HD vs. 20.05 +/- 3.19 micrograms/dL in
      controls).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570878
TI  - The free radical basis of air pollution: focus on ozone.

PMID- 8570879
TI  - Lung function measurement in general practice: a comparison of the Escort
      spirometer with the Micromed turbine spirometer and the mini-Wright peak flow
      meter.
AB  - It is important that new types of spirometer for widespread clinical use are
      pragmatically evaluated in primary care. This study compared measurements taken
      by a new portable Fleisch pneumotachograph spirometer (known as the Escort) with
      those of the commonly used mini-Wright peak flow meter and the Micromed Pocket
      turbine spirometer. A pragmatic study was conducted in two phases during routine
      surgeries at Aldermoor Health Centre, Southampton. Phase I compared the new
      spirometer with the mini-Wright peak flow meter and Phase 2 compared the new
      spirometer and the turbine spirometer. One hundred patients aged 5-88 years (56
      patients with a history of chronic respiratory complaints and 44 patients
      without) entered Phase 1, and 100 patients aged 6-82 years (62 patients with a
      history of chronic respiratory complaints and 38 patients without) entered Phase
      2. Each patient contributed only once to each phase, but some entered both phases
      on separate occasions. Ninety-five percent limits of agreement (mean +/- SD) were
      wide for all comparisons. Graphical plots revealed trends towards higher Escort
      values as mean values rose compared with both mini-Wright and turbine readings
      for peak expiratory flow rate and forced expiratory volume in one second.
      Possible over-reading of peak expiratory flow rate with the mini-Wright meter at
      low mean values was also seen. Readings taken with these different types of meter
      cannot be interchanged with confidence in clinical practice. The clinical
      significance of the theoretically more accurate measures of lung function
      produced with the new meter, and indeed of spirometry itself, needs further
      investigation.

PMID- 8570880
TI  - Asthma management and morbidity in Australian general practice: the relationship
      between patient and doctor estimates.
AB  - The aims of this study were to describe asthma management and morbidity in
      patients attending general practitioners in Australia, and to assess the
      relationship between patient reports and those of their general practitioner
      (GP). The sample comprised consecutive patients attending 46 general
      practitioners chosen at random in five regions of New South Wales, Australia. A
      total of 4538 patients were screened, 607 (13.4%) reported ever having diagnosed
      asthma, and the 501 who reported asthma in the previous 12 months completed a
      detailed questionnaire. Three hundred and thirty-four patients also had
      information about their asthma management recorded by their GP. The patient
      questionnaire asked about asthma symptoms, therapy, lung function measurement,
      and asthma-related morbidity. The GP questionnaire asked the doctor to record
      similar information about the patients. Two-thirds of the patients used regular
      inhaled beta 2-agonist medication, and one-half reported using preventive
      therapy. Only 24% owned a peak flow meter and 9% had a written plan of action for
      asthma attacks. Although preventive therapy and airway function assessment were
      more common in those with frequent symptoms (> 2-3 times per week), this group
      were still sub-optimally managed. In the matched sample (n = 334), doctors
      reported prescribing bronchodilator and preventive medication, measuring airway
      function and recommending peak flow meter use more often than suggested by
      patient-reported data. The study concludes that many patients do not attend for
      regular review, and that management remains sub-optimal, particularly in young
      adults. Data from patient surveys may underestimate clinical practice, as
      assessed from doctors' records. This should lead to patient-derived estimates of
      management being interpreted with caution in epidemiological studies. Further
      attention to patient understanding and compliance with prescribed asthma
      management advice is needed in order to better manage asthma in the community.

PMID- 8570881
TI  - Patient satisfaction with information provided at an outpatient clinic for
      respiratory diseases.
AB  - A survey of 374 unselected patients attending the Respiratory Outpatient
      Department of a teaching hospital revealed that most patients reported receiving
      information about the treatment of their disease, but only one-quarter received
      information about its prognosis. Patients reported receiving satisfactory answers
      to their requests for information on most occasions, and the overall satisfaction
      rate with information offered was 88.3%. Patients who had attended the clinic on
      five or more occasions felt that they had received more information on all items
      compared with those with fewer than five visits, although the increase was
      statistically significant only for information on treatment. Patients over 75
      years of age generally reported less information than younger patients. The great
      majority (88.4%) of patients preferred verbal information, but 23% also expressed
      a desire for written information as well. More attention should be paid to the
      needs of the elderly and to education about the nature and prognosis of disease.
      Printed material should also be more widely used.

PMID- 8570882
TI  - Additive effect of continuous low-dose ofloxacin on erythromycin therapy for
      sinobronchial syndrome.
AB  - It has been established that long-term low-dose erythromycin therapy (EM therapy)
      is very effective for sinobronchial syndrome, a common condition in Japan
      characterized by chronic upper and lower airway inflammation. The effect does not
      result from its bacteriocidal activity and the detailed mechanisms are not known.
      It takes 3-6 months for EM therapy to improve the symptoms. This study was
      designed to evaluate the additive effect of continuous low dosage or intermittent
      usual dosage of ofloxacin (OFLX) on EM therapy in patients with sinobronchial
      syndrome. Patients with sinobronchial syndrome were randomly allocated to receive
      one of the following four regimens. Patients in Group A received both low-dose
      OFLX and EM therapy daily for 6 months. Patients in Group B received EM therapy
      and intermittent treatment of OFLX for 6 months. Patients in Group C underwent EM
      therapy for 6 months. Patients in Group D received neither OFLX nor EM therapy.
      All patients were given carbocystein for more than 2 months before starting each
      treatment and during the study period. In patients receiving OFLX and/or EM
      therapy, these antimicrobial agents were well-tolerated during the treatment
      period. Amount of sputum in the morning was significantly less in Group C than in
      Group D after 3-6 months, and decreased significantly in Group A as compared with
      Group B after 2 weeks, Group C after 2 weeks to 2 months, and Group D after 2
      weeks to 6 months. Other symptoms such as number of expectorations, difficulty of
      expectoration and severity of cough also improved rapidly in Group A. These
      findings suggest that it is useful to add low-dose OFLX to EM therapy for
      sinobronchial syndrome, especially within 1-2 months from starting treatment, and
      it may be cost-effective as this combination therapy can shorten the treatment
      period of EM therapy.

PMID- 8570883
TI  - Prevalence of asthma and asthma-like symptoms in three French cities.
AB  - BACKGROUND: This study is part of the European Community Respiratory Health
      Survey (ECRHS), which uses a common methodology in different areas throughout the
      world. This paper describes the prevalences of reported asthma, asthma-like
      symptoms and nasal allergies, their relationships to age group and sex, and the
      relationships of asthma-like symptoms to current asthma, in the general
      population aged 20-44 years of three French urban areas. METHODS: The study
      population of 2804 subjects in Grenoble, 3774 in Montpellier and 3152 in Paris
      (18th district), randomly selected from electoral rolls, answered a postal
      questionnaire (stage I of ECRHS). The response rates were 77.8%, 68.6% and 74.4%,
      respectively. RESULTS: The prevalences were approximately 14% for wheezing, 16%
      for chest tightness and 4.5% for nocturnal shortness of breath in the three
      areas. Asthma attacks in the last 12 months were reported by 2.7% of subjects in
      Grenoble, 3.5% of subjects in Montpellier and 4.0% of subjects in Paris (P =
      0.02). For nasal allergies, the prevalences were 28.0%, 34.3% and 30.8%,
      respectively (P < 0.001). Asthma was inversely correlated to age (higher
      prevalence in the youngest) but was not related to sex. Neither age distribution
      nor sex ratio explained the differences between areas. Among the asthma-like
      symptoms, wheezing and nocturnal shortness of breath correlated strongly with
      asthma, chest tightness correlated moderately and nocturnal coughing correlated
      poorly. CONCLUSION: The prevalences observed were higher than expected from
      previous comparable French studies in young adults. These results are consistent
      with the hypothesis of a recent increase of asthma and allergies.

PMID- 8570884
TI  - Occupational asthma due to chloramine-T solution.

PMID- 8570886
TI  - Kikuchi's disease presenting as bilateral hilar lymphadenopathy.

PMID- 8570885
TI  - Endobronchial non-Hodgkin's lymphoma in an AIDS patient.

PMID- 8570887
TI  - Primitive neuroectodermal tumour of the chest wall (Askin tumour): CT and
      roentgenographic findings in a 51-year-old male.

PMID- 8570888
TI  - Problems encountered using nebulized medications in hospitals.

PMID- 8570889
TI  - Cattle TB: 'VL, open' cases ... or 'NVL, non-infectious' cases?

PMID- 8570890
TI  - Granulocyte-macrophage colony stimulating factor and bronchial asthma--a
      hypothesis for novel therapeutic options.

PMID- 8570891
TI  - Idiopathic pulmonary haemosiderosis (IPH)

PMID- 8570892
TI  - Air filtration units.

PMID- 8570893
TI  - Banning smoking in hospitals.

PMID- 8570894
TI  - Fibres, particles and the lung: new perspectives. 14th Summer meeting of the
      British Association for Lung Research, Edinburgh, United Kingdom, 11-12 September
      1995. Abstracts.

PMID- 8570895
TI  - [Transfusion savings in orthopedic surgery. Round table].

PMID- 8570896
TI  - [Symposium: posterior cruciate ligament].

PMID- 8570897
TI  - [Shoulder prosthesis].

PMID- 8570898
TI  - [The Pain Perception Scale--a differentiated and change-sensitive scale for
      assessing chronic and acute pain].
AB  - Presented is a diagnostic instrument to assess chronic and acute pain, that
      allows multifaceted and standardized quantification of pain experience. This tool
      -the Pain Experience Scale ("Schmerzempfindungsskala"--SES)--measures two
      dimensions of subjectively felt pain, the affective characterization as well as
      modes of sensory characterization of pain. Applications range from degenerative
      or inflammatory joint and back pain to headache/migraine, neuropathias and other
      pain-related diseases (age 16 to 80 years). Completion, evaluation, and
      interpretation are done easily. Scale development had comprised 3 steps of
      research for obtaining a model of invariant structure and homogenous factors.
      Scale analyses demonstrated the instrument's reliability, and numerous studies
      illustrated the validity of the scale. They showed that factorial, convergent and
      discriminant validity can be regarded as given. Moreover, the scale proved to be
      sensitive in experimental pain studies. Additionally, specific patterns of scores
      could be observed validly for 18 different groups of disease/pain. Special
      efforts were invested to show its sensitivity to change in the course of pains.
      Here, the Pain Experience Scale proved to be suitable in postoperative pain, drug
      based pain therapies, different psychological pain management approaches,
      physiotherapeutic prevention, and a multimodal treatment programme of a
      specialized pain clinic. In German-speaking countries, the SES has been in use
      for several years as a well-proven instrument in medical care, clinical research
      as well as field evaluation.

PMID- 8570899
TI  - [Can disabled persons have "full social value"?].
AB  - Starting out from some value theory-based considerations, the author subsequently
      questions the concept of being "fully adequate" ("vollwertig", literally: "full
      value") in light of the human condition, and in particular in its relation to
      persons with disabilities. In the context of biotic, human life as a fundamental
      value, a critical discussion ensues of the position held by P. Singer concerning
      person status of beings, with the degree of biotic perfection of man the focal
      point of discussion here. Extensive thought is given to the rank of human
      achievement within the social value system, and its meaning to persons with
      disabilities. Achievement is accepted as a value, given full awareness of its
      relativity. For persons with profound disablement, for very old and frail
      persons, an entitlement, without any counter consideration required, to
      recognition and valuation of their existence is posited, which includes the need
      to create overall conditions enabling humane dying in light of the concrete
      circumstances.

PMID- 8570900
TI  - [Occupational rehabilitation of psychiatric patients in the Michaelshoven/Cologne
      vocational training center--an integrated overall concept].
AB  - Vocational retraining centres, sui generis, belong to those vocational
      rehabilitation facilities where disabled adults are afforded an opportunity for
      comprehensive occupational reorientation, facilities that operate on the
      principle of "dual training under one roof", i.e. combine practical and
      theoretical contents, which documents their close linkage with the mainstream
      vocational education system practiced in Germany. An essential modification has
      for some years now been introduced at the Michaelshoven/Cologne vocational
      retraining centre: the traditional conveyance of skills and knowledge (i.e.,
      acquisition of technical competence) has been replaced by attainment of
      occupational action competence as the focus of rehabilitative efforts. Hand in
      hand with this concept rooted in the principle of client-concentration, comes
      implementation of the principles of integration and holistic approach.
      Integration means that rehabilitees with mental illness participate in the
      rehabilitation programmes alongside rehabilitees without mental illness. The
      holistic approach is expressed in a number of closely coordinated elements
      ensuring that the specific configuration of persons with mental illness and their
      way of life are taken into consideration from the very beginning of their stay in
      the Michaelshoven/Cologne vocational retraining centre. Along with in-depth talks
      at entry and specific vocational guidance for individuals with mental illness,
      these elements inter alia include: pre-rehabilitation adjustment, pre
      rehabilitation course, an extramural industrial practical, action-oriented
      training methods throughout, and systematic placement assistance and support--in
      line with the vocational retraining centre's motto of "picking up our
      rehabilitees right where they stand".

PMID- 8570901
TI  - [An integrated concept for vocational rehabilitation of brain injured patients--a
      catamnestic study of occupational outcome 1 to 2 years later].
AB  - Presented is a vocational reintegration concept for clients following
      craniocerebral trauma and other acquired brain damage. Close dovetailing of
      vocational and therapeutic measures is advocated, as it is mostly the
      neuropsychological disorders or problems in behaviour and emotional experience
      that stand in the way of returning to work. A work experience and adjustment
      setting holds particularly great potential for addressing these difficulties in a
      day-to-day life-related, remedial manner. Another focus is follow-up care of
      those clients who have returned to competitive employment. These clients are
      called on regularly at their workplace by programme vocational
      guidance/vocational assessment staff; necessary adaptations are carried out,
      difficulties dealt with, and possible solutions sought jointly with the employer.
      A catamnestic study was undertaken to verify how many of the clients included in
      the programme had achieved long-term resettlement. It was found that the great
      majority of those who had returned to their former job, have retained their
      employment some one to two years later, with most of them working at a lower
      level than before the event. Clients unable to return to their former employer
      had mostly been pensioned despite the presence of partial working capacity.

PMID- 8570902
TI  - [The need for work--experiences from a day-care center].
AB  - The concept of a vocational day-care centre for persons with chronic mental
      illness is discussed. Work is done with clay, which enables a supply with both
      very simple and very sophisticated tasks. Clients are able to clearly realize the
      results of their joint efforts. Analysis of attendance at the centre reveals that
      especially those who had spent longer periods of time in psychiatric hospital and
      are already receiving a disability pension came to work most regularly. These
      findings show that even for those who have definitely withdrawn from gainful
      employment, individually adapted work opportunities nevertheless remain of
      considerable importance.

PMID- 8570903
TI  - [Possibilities for geriatric psychosomatic rehabilitation].
AB  - Starting out from the insufficiencies in the psychotherapeutic care for elderly
      patients, the treatment possibilities available in psychosomatic clinics are
      delineated. Utilization of these possibilities by the elderly is pointed out,
      some fundamental aspects of gerontopsychosomatic rehabilitation are discussed,
      and it is shown that specific aspects must be considered in the treatment of this
      population.

PMID- 8570904
TI  - [Social rehabilitation through sports].
AB  - The contribution community disabled sports is making towards comprehensive
      rehabilitation of people with disabilities is interpreted much too narrowly by
      the statutory definition of rehabilitation sports. In the member clubs of
      Deutscher Behinderten-Sportverband, the German disabled sports association,
      severely disabled individuals rediscover their potential and self-worth, which
      may entail self-determination, solidarity with others, and genuine social
      integration. Renewed awareness of the traditional values of German disabled
      sports as a self-help movement of those concerned, and characterization of
      rehabilitation as a complex learning process towards regaining personal autonomy-
      both call for a thorough reconsideration of ambulatory disabled sports in
      organizational and funding respects.

PMID- 8570905
TI  - [Greater mobility in Europe--current European developments for barrier-free
      transportation].
AB  - Harmonization and coordination at the European level of all measures taken on
      behalf of disabled persons is an indispensable prerequisite for enabling
      convergence of conditions to occur at the highest possible level. This is true
      above all for the initiatives and activities that go beyond the specific domain
      of social policy, and in particular for the developments in the field of
      accessible, barrier-free environmental design. The Federal Rehabilitation Council
      (Bundesarbeitsgemeinschaft fur Rehabilitation) cooperates in a number of European
      activities directed at achieving accessibility of regional, rail and air
      transport, as well as of passenger ships. This involvement is aimed at bringing
      long-term national experience in this respect to bear in the context of European
      developments, and at inclusion of the standards already achieved in the transport
      sector in Germany also in the efforts undertaken toward accessibility in European
      transport.

PMID- 8570906
TI  - [Comment on federal development of a regulation for reforming the German social
      security law 18 July 1995. German Society for Rehabilitation of Disabled e. V].

PMID- 8570907
TI  - [European meeting of the ICTA Commission of RI, June 1995 in Tallin, Estland].

PMID- 8570908
TI  - Ischemia reperfusion of the pancreas: a new in vivo model for acute pancreatitis
      in rats.
AB  - Based on the concept that ischemia is an important factor in the pathogenesis of
      acute pancreatitis, we developed a new model of complete ischemia/reperfusion of
      the pancreas in the rat. The aim of this study was to investigate the
      microcirculation of the pancreas after complete and reversible ischemia at
      different times after reperfusion by using intravital fluorescence microscopy. In
      addition, the effect of ischemia/reperfusion on the pancreas was assessed by
      means of light and electron microscopy and measurement of serum pancreas amylase
      concentration. In 35 adult Sprague-Dawley rats ischemia of the pancreas was
      induced by temporary occlusion of the four supplying arteries. Sham-operated
      animals served as controls (group A). After periods of 30 min (group B), 60 min
      (group C) or 120 min (group D) of ischemia the organ was reperfused. To exclude
      the influence of hypovolemia on microcirculation in group E (120 min ischemia)
      hydroxyethylstarch (HES) was given i.v. to maintain central venous pressure at
      baseline values. For intravital fluorescence microscopy the pancreas was
      exteriorized on a stage and quantitative analysis of microcirculation, including
      functional capillary density and leukocyte-endothelium interaction, was performed
      after 30 min, 1 h and 2 h of reperfusion. Serum pancreas-amylase was measured at
      control (prior ischemia) and at 2 h after reperfusion. Tissue samples for light
      and electron microscopy were taken 2 h after reperfusion. In sham-operated
      animals, functional capillary density (FCD) remained within baseline values (FCD
      407.7 +/- 9 cm-1) during reperfusion. Dependent on the time of ischemia and time
      of reperfusion a gradual reduction in functional capillary density was observed;
      after 2 h of ischemia only 35% of capillaries were perfused (FCD 140.9 +/- 28.3
      cm-1). Reduced functional capillary density was associated with an increase of
      perfusion heterogeneity to a maximum of 0.65 +/- 0.12, as against 0.13 +/- 0.02
      in control animals. With a 2 h ischemia leukocyte-endothelium interaction was
      enhanced after 0.5 h of reperfusion (8-fold increase of adherent leukocytes in
      comparison to control) followed by a further significant increase until 2 h after
      the beginning of reperfusion. Amylase concentration after ischemia of 2 h (2967
      +/- 289 U/l) was significantly higher as compared to controls (1857 +/- 99 U/l).
      Differences between group E and D were not observed. Pancreatic tissue injury was
      ascertained by histopathological studies. These results indicate that complete
      ischemia/reperfusion of the pancreas induces pancreatic microvascular failure.
      The severity of changes depends on duration of ischemia and duration of
      reperfusion. The morphological and biochemical changes suggest that
      ischemia/reperfusion causes an inflammatory reaction as observed in acute
      pancreatitis.

PMID- 8570909
TI  - Increased capillary endothelial leakage in portal hypertensive gastric mucosa:
      fluorescence microscopy in CCl4-induced cirrhotic rats.
AB  - Since portal hypertension affects the gastric mucosa, leading to congestive
      gastropathy and thus to increased incidence of bleeding, it is one of the
      possible causes of increased permeability of gastric mucosal capillaries. The aim
      of this study was the quantitative assessment of the permeability of the gastric
      mucosal endothelial cells. Eight CCl4-induced cirrhotic rats and eight matched
      controls were subjected to i.v. injection of FITC-albumin, and a morphometric
      evaluation of fluorescence in serial histological sections of the gastric mucosa
      was performed by a video image analysis system. Fluorescence was found to be
      0.351 +/- 0.01% of the area scanned in experimental animals versus 0.073 +/-
      0.005% in controls, i.e. it was significantly increased by the treatment, which
      implies a significant endothelial leakage into the extravascular space.

PMID- 8570910
TI  - Carbohydrate-binding proteins (plant/human lectins and autoantibodies from human
      serum) as mediators of release of lysozyme, elastase, and myeloperoxidase from
      human neutrophils.
AB  - Analysis of cell surface glycosylation not only provides information about cell
      properties such as their state of differentiation or histogenetic lineage. The
      carbohydrate chains also provide potentially functional binding sites to
      endogenous carbohydrate-binding proteins. This interaction can elicit consequent
      signalling processes. Because of the importance of neutrophils in the host
      defence system, we monitored the effect of the binding of such sugar receptors to
      their cell surface on the release of the enzymatic activities of lysozyme,
      elastase, and myeloperoxidase. Besides the mannose-binding lectin concanavalin A
      and the immunomodulatory alpha/beta-galactoside-binding lectin from Viscum album
      L., three preparations of human sugar receptors - beta-galactoside-binding lectin
      (M(r) 14 kDa) and two affinity-purified polyclonal IgG fractions from serum with
      the capacity to recognize alpha- or beta-galactosides, respectively - were used.
      Two animal lectins from chicken liver and intestine that bind beta-galactosides,
      as well as the lectin-like human serum amyloid P component, were included in
      order to assess the importance of slight differences in ligand recognition.
      Cytochalasin B-enhanced enzyme release was invariably seen with the two plant
      lectins and the chicken liver beta-galactoside-binding lectin, but the related
      intestinal lectin did not increase enzyme release. The mammalian homologue of
      these avian lectins triggered lysozyme secretion, and the lactoside-binding IgG
      fraction enhanced the amount of extracellular elastase activity slightly but
      significantly. Thus, the actual lectin, not the nominal specificity of sugar
      receptors, is crucial for elucidation of responses. Due to the highly stimulatory
      activity of the two plant lectins, neutrophils from patients with non-cancerous
      diseases and from patients with lung cancer were monitored for the extent of
      lectin-mediated enzyme release. Only the concanavalin A-mediated reactivity of
      the neutrophils was associated with the type of disease.

PMID- 8570911
TI  - The effects of experimental splenic autotransplantation and imipenem-cilastatin
      treatment in postsplenectomy Pseudomonas aeruginosa sepsis.
AB  - Male Wistar albino rats were allocated to three groups-sham operated (n: 10),
      splenectomized (n: 20) and splenic autotransplanted (n: 10). Twelve weeks after
      operation, all were challenged with 1.8 x 10(8) cfu/ml Pseudomonas aeruginosa
      intranasally. Half of the splenectomized rats received imipenem-cilastatin after
      2 h of bacterial challenge. Mortality was then observed for the next 12 days. All
      animals were autopsied and liver, kidney, spleen and lung specimens were
      processed for microbiological culture and histopathological examination. In 80%
      of autotransplanted rats, splenic tissue regeneration was histopathologically
      verified. Hemoglobin oxidation of erythrocytes increased in splenectomized rats
      and remained close to control levels in the autotransplanted group. No
      significant difference was detected between IgM levels of splenectomized and
      autotransplanted groups. Mortality rates were the same for all groups, except
      that splenectomized animals given antimicrobial therapy had increased survival
      rates. In conclusion, it is likely that the spleen has no role in protection
      against pulmonary sepsis and that only appropriate antimicrobial therapy can
      protect the splenectomized host from Pseudomonas sepsis.

PMID- 8570912
TI  - The role of the vascular endothelium in the contractile responses of human
      chorionic plate artery in pre-eclampsia to prostaglandin F2 alpha, 5
      hydroxytryptamine, and potassium chloride.
AB  - This study characterises the reactivity of chorionic plate artery in pre
      eclampsia to prostaglandin F2 alpha (PGF2 alpha), 5-hydroxytryptamine (5-HT), and
      potassium chloride (KCl) and examines the role of the vascular endothelium in
      these responses. Ring segments of the chorionic plate arteries of women after
      normal and pre-eclamptic pregnancies were contracted by PGF2 alpha, 5-HT, and
      KCl. The experiments were carried out in the presence and absence of endothelium,
      and on intact rings treated with 10(-6)M indomethacin. The maximal contractile
      responses of rings from pre-eclamptic women to 5-HT, PGF2 alpha, or KCl were
      significantly greater than those of rings from normotensive pregnant women. The
      EC50 values of responses were significantly lower in rings from pre-eclamptic
      subjects. Endothelium removal and treatment of the rings with indomethacin had no
      effect on the contractile responses of rings from normotensive pregnant women to
      all the agents, but significantly increased the EC50 value and decreased the
      maximal contractile responses of rings from pre-eclamptic women to 5-HT and PGF2
      alpha. While de-endothelialisation increased the EC50 value for responses of the
      rings from pre-eclamptic women to KCl, pretreatment with indomethacin did not
      significantly affect the KCl-induced responses. The results of the study suggest
      that pre-eclampsia enhanced the reactivity of human chorionic plate artery to 5
      HT, PGF2 alpha, and KCl through the involvement of endothelial derived
      contracting factors. The increased responses to 5-HT and PGF2 alpha were
      inhibited by indomethacin, but those to KCl were not.

PMID- 8570913
TI  - NO in the lung.
AB  - In the lung, nitric oxide (NO) derives from several cellular sources, forming
      networks of paracrine communication. In pulmonary vessels, NO produced by
      endothelial cells is a powerful vasodilator. In the airways, NO originates from
      epithelial cells and from adventitial nerve endings to induce smooth muscle
      relaxation. Activated macrophages can also produce large quantities of NO during
      lung immunological reactions. In the normal pulmonary circulation, NO not only
      mediates vasodilation, but also opposes vasoconstriction, prevents platelet
      adhesion, controls growth of smooth muscle and influences the composition of the
      extracellular matrix. During exposure to chronic hypoxia, impaired endothelial NO
      production contributes to the increased vasomotor tone and vascular remodelling
      leading to sustained pulmonary hypertension. Exogenous NO gas delivered via the
      airspaces is a selective pulmonary vasodilator. Inhaled NO is now used as a
      therapy to treat various forms of pulmonary hypertension and to improve arterial
      oxygenation during lung injury.

PMID- 8570914
TI  - A differential bronchomotor response to cooling and drying the upper airway.
AB  - The present study aimed to compare the reflex bronchoconstrictor effects of upper
      airway applications of dry airstreams with equivalent cooling produced by cold
      isotonic and hypertonic saline solutions in anaesthetized rabbits. A method of on
      line, breath by breath analysis of lung mechanics was used. The changes in total
      lung resistance (RL) and dynamic lung compliance (Cdyn) produced by dry
      airstreams and by cold hypertonic saline were greater than those induced by cold
      isotonic saline. Warm isotonic saline and supersaturated airstreams were
      ineffective. These results implicate osmotic disturbances in the response to dry
      airstreams. The response to dry airflow was abolished by section of the superior
      laryngeal nerves, by vagotomy and by atropine, suggesting a central cholinergic
      reflex mechanism is involved. Phosphoramidon had no effect, indicating that
      tachykinins are unlikely to play a role in this particular reflex.

PMID- 8570915
TI  - Recurrent laryngeal nerve activation by alpha 2 adrenergic agonists in goats.
AB  - The purpose of this study was to test the hypothesis that respiratory and apneas
      induced by alpha 2 agonists in anesthetized goats are associated with an increase
      of upper airway expiratory-related activity, rather than a general depression of
      breathing. Activities of phrenic (Phr) and recurrent laryngeal nerves (RLN) were
      recorded in response to the alpha 2 agonists clonidine (0.5-3.0 microgram.kg-1
      i.v.) or guanabenz (7.0-20.0 micrograms.kg-1 i.v.) in ten chloralose-anesthetized
      goats. Injection of either alpha 2 agonist resulted in respiratory arrhythmias
      with a greater than seven-fold increase in TE and a 30% reduction in TI. During
      apneas RLN expiratory-related activity remained tonic until the next Phr burst,
      consistent with our hypothesis. Cessation of Phr activity during hypocapnia also
      resulted in a tonic increase of RLN expiratory activity; and injection of NaCN
      (50 micrograms.kg-1 i.v.) increased Phr and RLN inspiratory activities, while
      attenuating RLN expiratory-related activity. Inspiratory and expiratory-related
      activity of RLN motoneurons appear to be reciprocally modulated by alpha 2
      agonists or changes in central or peripheral chemoreceptor drive. The results
      indicate that central apneas and respiratory arrhythmias may be associated with
      alpha 2-adrenoceptor modulation of laryngeal expiratory-related activity.

PMID- 8570916
TI  - A protocol for determining the shape of the ventilatory response to hypoxia in
      humans.
AB  - The ventilatory response to isocapnic hypoxia is biphasic, which makes any
      experimental assessment of the relationship between the acute (peak) ventilatory
      response and the level of hypoxia difficult. This study explored whether one
      particular protocol could be useful for determining this relationship. The
      protocol consisted of exposing subjects to seven different levels of isocapnic
      hypoxia, each of which lasted 50 sec. In order to test whether the order of the
      hypoxic exposure had any effect on the outcome, the steps were performed both in
      increasing and decreasing severity of hypoxia, and the ventilatory responses
      compared. Twelve subjects were studied, and each test was repeated four times in
      each subject. PETCO2 was held at 2 mmHg above resting throughout. The
      ventilations obtained at the lowest level of PETO2 employed were clearly
      different between the two protocols. However, provided that these ventilations
      were excluded, no significant differences were present between the results from
      the ascending and descending exposures (ANOVA). This finding suggests that the
      rate of change of PO2 in these protocols was sufficiently slow for a full
      ventilatory response to develop, but also sufficiently fast to prevent
      significant ventilatory depression from occurring.

PMID- 8570917
TI  - The nature of breathing during hypocapnia in awake man.
AB  - We have studied post-hyperventilation breathing pattern in eight, awake, healthy,
      naive volunteers after 5 min voluntary or mechanical hyperventilation during
      normocapnia (PETCO2 = 38 mmHg) and 'hypocapnia (24 mmHg). Breathing was monitored
      for 10 min post-hyperventilation, 'non-invasively', using calibrated respiratory
      inductance plethysmography; wakefulness was confirmed with
      electroencephalography. Comparison of breathing following hypocapnic voluntary
      hyperventilation with that following hypocapnic mechanical hyperventilation
      indicated that ventilation was elevated following voluntary hyperventilation;
      this would suggest that 'after-discharge' exists in man following active
      hyperventilation, even during hypocapnia. In the absence of 'after-discharge'
      (i.e. following mechanical hyperventilation), hypocapnia was clearly associated
      with hypoventilation. Apnoeas (increased TE) were present during hypocapnia; but
      neither the duration nor the occurrence of apnoea was related to the absolute
      level of PETCO2. Most notable, was the marked increase in breath-by-breath
      variability of TI, TE and VT during hypocapnia. The increased variability of
      breathing during hypocapnia may reflect fluctuations in behavioural drives
      associated with wakefulness.

PMID- 8570918
TI  - Cardiorespiratory and sleep-wake behavior in developing swine: kappa-opioid
      influence.
AB  - Effects of specific kappa-opioid antagonism with norbinaltorphimine (NorBNI) on
      sleep-wake state, blood pressure and heart rate, and on diaphragmatic and
      posterior cricoarytenoid electromyographic activities were assessed in 3 to 13
      and 23 to 33 day-old, chronically instrumented, unanesthetized piglets.
      Preliminary experiments established the pharmacodynamics and dose-response for
      NorBNI. In the main study, each piglet was studied twice daily, once before and
      once after 3.7 mg kg-1 NorBNI iv, for up to five consecutive days. During each
      study session, piglets underwent 10 min trials with 21% O2 in 79% N2 followed by
      10% O2 in 90% N2 while lying in a sling within a plexiglass box. Sleep-wake
      distribution and cardiorespiratory functions matured with age. NorBNI produced a
      modest increase of arterial pressure and heart rate in the older group only, and
      altered neither state nor respiration at either age. These results suggest that,
      in the developing piglet model, the kappa-opioid system influences neither
      breathing nor state, but modulates cardiovascular regulation to a modest degree
      and later in ontogeny.

PMID- 8570919
TI  - Costal diaphragm blood flow heterogeneity at rest and during exercise.
AB  - To gain insight into diaphragm functional heterogeneity, blood flow (expressed as
      ml.min-1 x 100 g-1) was measured using radiolabeled microspheres in the ventral,
      medial, and dorsal regions of the costal diaphragm and in the crural diaphragm of
      sedentary control (S) and exercise trained (ET) female Wistar-Kyoto rats at rest
      and during treadmill exercise. ET animals had performed moderate intensity
      exercise training on a motorized treadmill (22 m/min, 10% grade, 60 min/d) for 12
      months, while S were cage-confined. The efficacy of exercise training was
      demonstrated by a 12% increase (P < 0.05) in ventricular weight-to-body weight
      ratio and increases (P < 0.05) in citrate synthase activity in hindlimb skeletal
      muscles of ET. At rest, blood flow in the ventral costal diaphragm (16 +/- 1)
      averaged approximately 61% of that in the medial (26 +/- 3) and dorsal (25 +/- 2)
      costal regions (P = 0.035), and crural diaphragm flow was 23 +/- 3. During
      treadmill exercise (5 min at 22 m/min, 10% incline), blood flow increased an
      average of 5-fold (P < 0.001) throughout the diaphragm, but the heterogeneous
      flow pattern persisted; i.e., blood flow remained lower (P = 0.003) in the
      ventral region (77 +/- 7) than either the medial (135 +/- 15) or dorsal (127 +/-
      11) costal regions. Flow in the crural diaphragm during exercise was intermediate
      (105 +/- 9). Exercise training did not alter either the magnitude of blood flows
      or the flow distribution pattern within the diaphragm. Citrate synthase activity
      was two-fold that of the plantaris muscle and was uniform across the ventral,
      medial, and dorsal costal and the crural diaphragm of a second group of age
      matched rats (P = 0.57). These data demonstrate that, although oxidative capacity
      is uniform throughout the diaphragm, there is a significant regional
      heterogeneity of blood flow within the rat diaphragm both at rest and during
      locomotory exercise. The greater flow in the medial and dorsal regions of the
      costal diaphragm suggests that these regions sustain a greater portion of the
      inspiratory work load at rest and during exercise compared to the ventral region.

PMID- 8570920
TI  - Cold acclimation and endurance training in guinea pigs: changes in daily and
      maximal metabolism.
AB  - The physiological effects of training or cold acclimation on maximal oxygen
      uptake (VO2,max) and average daily metabolic rate (VO2,dav) of a small mammal,
      the guinea pig, are described. Young male guinea pigs were assigned to three
      experimental groups; control, endurance trained (70% VO2,max) or cold acclimated
      (5-7 degrees C) for six weeks. Measurements of VO2,max and VO2,dav were made
      before and after the treatments. VO2,max increased significantly in cold
      acclimated (+29%) and endurance trained (+23%) animals and was achieved at a
      higher maximal running speed compared to post-treatment controls. Maximal blood
      lactate concentration was significantly higher in cold acclimated compared to
      endurance trained animals. Endurance trained animals had a reduced VO2,dav
      compared to control animals, whereas cold acclimation raised VO2,dav in the cold
      as expected, but also at room temperature. All three groups showed a daily
      pattern in metabolic rate (night > day). In conclusion, both endurance training
      and cold acclimation lead to enhanced VO2,max and changes in resting oxygen
      consumption throughout the day.

PMID- 8570921
TI  - Cold acclimation and endurance training in guinea pigs: changes in lung, muscle
      and brown fat tissue.
AB  - The effects of an intermittent high intensity stimulus (running) or a chronic low
      intensity stimulus (cold acclimation) of oxidative metabolism on maximal oxygen
      uptake (VO2,max), lung O2 diffusing capacity (DLO2) and skeletal muscle as well
      as fat tissue mitochondrial content in growing guinea pigs are described. Young
      male guinea pigs were assigned to three experimental groups (n = 5): control (C),
      endurance trained (T; at 70% VO2max) or cold acclimated (CA; 5-7 degrees C) for
      six weeks. Animals were sacrificed at the end of the experimental period and
      tissue for morphometric analysis of the lung, muscle and interscapular fat was
      sampled. T and CA animals significantly increased weight specific VO2max by 23%
      and 29%, respectively. Despite a significant increase in absolute lung volume in
      T (+10%) and in weight specific lung volume in CA (+20%) neither absolute nor
      weight specific DLO2 was significantly affected by the experimental treatments.
      In trained animals the total volume of mitochondria remained unchanged in samples
      representative for the entire musculature but was significantly increased in M.
      vastus intermedius (+72%). Intramyocellular lipids increased significantly both
      in M. vastus intermedius (+244%) as well as in the whole body musculature
      (+164%). Cold acclimation increased the mitochondrial content of the
      interscapular fat pad by approximately 20-fold but had no effect on total
      mitochondrial volume in muscle. We conclude that the increase in oxygen demand
      resulting from exercise training or from cold acclimation could be accomodated by
      the existing lung diffusing capacity and did not induce a global change of
      oxidative capacity in skeletal muscle tissue in growing guinea pigs. Exercise
      training caused oxidative capacity to increase only in a locomotor muscle
      activated during running whereas cold acclimation greatly increased interscapular
      fat tissue oxidative capacity.

PMID- 8570922
TI  - Cytoplasmic motility reflects phagocytic activity in alveolar macrophages from
      dog lungs.
AB  - To determine whether cytoplasmic motility relates to phagocytic activity of
      alveolar macrophages (AM), we measured the remanent field strength (RFS) from the
      AM containing Fe3O4 particles (5 x 10(6) cells) and the number of phagocytized
      fluorescent latex spheres in the AM without having Fe3O4 particles (10(6) cells)
      harvested by broncho-alveolar lavage from dog lungs in vitro. Cytoplasmic
      motility was estimated from the relaxation rate (lambda o; min-1) calculated from
      the decay curve of RFS and the number of phagocytized latex spheres was counted
      using fluorescent microscopy after the addition of latex spheres (5 x 10(7)). The
      tumor necrosis factor increased both lambda o and the number of phagocytized
      latex spheres, and cytochalasin D and colchicine decreased them in a
      concentration-dependent fashion. Increases and decreases in lambda o induced by
      drugs paralleled the number of phagocytized latex spheres. These results suggest
      that cytoplasmic motility reflects phagocytic activity of AM and both cytoplasmic
      movement and phagocytosis may be regulated by a similar mechanism in the
      cytoskeletal system.

PMID- 8570923
TI  - Effects of platelet depletion on PMA-induced acute lung injury in awake sheep.
AB  - Little is known about the role of circulating platelets in PMA-induced lung
      injury in vivo. We investigated the effects of platelet depletion (PD) on the
      injury using seven unanesthetized sheep with lung lymph fistulas and eight other
      sheep for morphological study. PD diminished a decrease in the lymph to plasma
      concentration ratio (L/P) after 1 microgram/kg PMA treatment (n = 4) and caused
      more increases in lung lymph flow, L/P and lung lymph clearance after 5
      micrograms/kg PMA treatment (n = 3) than in control sheep. The high dose was
      lethal to platelet-depleted sheep. However, PD had no effects on pulmonary
      hemodynamics. Morphologically, alveolar hemorrhages and exudate, and bleb
      formation of type I epithelial cells were more prominent in the platelet-depleted
      sheep than in the control sheep. We conclude that circulating platelets have
      protective effects against PMA-induced lung injury but have little involvement in
      PMA-induced pulmonary hypertension.

PMID- 8570924
TI  - Cloud-to-ground lightning: mechanisms of damage and methods of protection.

PMID- 8570925
TI  - Central nervous system complications of lightning and electrical injuries.

PMID- 8570927
TI  - Neuro-otologic findings in the lightning-injured patient.
AB  - Although lightning injuries are common, neuro-otologic sequelae are infrequently
      reported. The most common otologic injury encountered in the lightning strike
      victim is tympanic membrane rupture; the most common vestibular disturbance
      documented is transient vertigo. A variety of other clinical findings have been
      described in this population of patients. They include sensorineural hearing
      loss, conductive deafness, tinnitus, basilar skull fracture, avulsion of the
      mastoid bone, burns to the external auditory canal, and peripheral facial nerve
      palsy. The initial treatment of the lightning strike victim consists of basic
      life support measures. Once stabilized, the patient should undergo a complete
      otologic and vestibular evaluation. The majority of otolaryngologic problems
      encountered can be managed expectantly, with periodic re-evaluation.
      Tympanoplasty should be delayed for 6 to 12 months because of the frequent delay
      in spontaneous healing.

PMID- 8570926
TI  - Peripheral nerve disorders in electrical and lightning injuries.

PMID- 8570928
TI  - Involuntary movement disorders following lightning and electrical injuries.

PMID- 8570929
TI  - Emergent care of lightning and electrical injuries.
AB  - High-voltage electrical injuries may be devastating, with extensive burns,
      cardiac arrest, amputations, and long, complicated hospitalizations. Low-voltage
      injuries, after other pathologic and high-voltage sources are ruled out, tend to
      be rather benign acutely although they may have significant long-term morbidity,
      including chronic pain syndromes. Lightning injuries affect 800 to 1000 persons
      per year. In lightning injury, cardiac arrest is the main cause of death, burns
      tend to be superficial, ad injuries often are what one would expect of short
      circuiting or overloading the body's electrical systems (tinnitus, blindness,
      confusion, amnesia, cardiac arrhythmias, and vascular instability). Although high
      voltage injuries may require the services of trauma surgeons, in general, therapy
      for low-voltage and lightning injury is supportive and involves cardiac
      resuscitation for the more seriously injured and supportive care for the less
      severely injured. Long-term problems from sleep disturbances, anxiety attacks,
      pain syndromes, peripheral nerve damage, fear of storms (for lightning patients),
      and diffuse neurologic and neuropsychologic damage may occur in both electrical
      and lightning patients. Other sequelae--such as seizures or severe brain damage
      from hypoxia during cardiac arrest and spinal artery syndrome from vascular spasm
      -are indirect results of electrical and lightning injury.

PMID- 8570930
TI  - Behavioral consequences of lightning and electrical injury.

PMID- 8570931
TI  - Demographics of lightning casualties.

PMID- 8570932
TI  - Structural changes after lightning strike, with special emphasis on special sense
      orifices as portals of entry.

PMID- 8570933
TI  - Do electromagnetic fields cause brain tumors and other cancers?

PMID- 8570935
TI  - A Doctor's Zeus story.

PMID- 8570934
TI  - Electrical safety measures for physicians using electromedical equipment.

PMID- 8570936
TI  - [Beware: progestins elevate body temperature!].

PMID- 8570937
TI  - [Effect of primary prevention of Pneumocystis carinii pneumonia on the inaugural
      clinical and biological presentation of AIDS: 624 cases (Aquitaine Cohort, 1985
      1994)].
AB  - In a cohort of HIV-infected patients, this study compares the clinical and
      immunological features at the time of AIDS diagnosis of patients who either
      received primary Pneumocystis carinii prophylaxis (P+; n = 335) or who did not (P
      ; n = 289). Frequency of P carinii pneumonia was lower in P+ than in P- patients
      (14.9% vs 26.0%; p < 0.001). Conversely, toxoplasmic encephalitis, esophageal
      candidiasis, cytomegalovirus disease and M avium complex disease were more
      frequent in P+ patients. CD4+ count (median/mm3) at the time of AIDS diagnosis
      was lower in P+ than in P- patients: 22 vs 97 (p < 0.001); this suggests that
      early intervention delays the onset of AIDS for about one year. While searching
      for new prevention strategies against other opportunistic infections, efforts
      should be expanded to improve prophylaxis of P carinii pneumonia which remains in
      France the most frequent first AIDS-related illness.

PMID- 8570939
TI  - [Drug-induced iatrogenic arterial diseases].
AB  - Several drugs have been shown to cause vasomotor troubles such as Raynaud's
      phenomenon, erythromelalgia, vasculitis, livedo reticularis, or acrocyanosis.
      Vascular symptoms may develop a few weeks or more after drug initiation,
      particularly when other drugs are associated than can potentiate vascular side
      effects. In this review, the authors described the main characteristics of drug
      induced vasculopathy, particularly those associated with ergotamine derivates,
      beta blocking agents or antineoplastic chemotherapy.

PMID- 8570938
TI  - [Right diaphragmatic kinetics measured by TM-mode ultrasonography with
      concomitant spirometry in normal subjects and asthmatic patients. Preliminary
      results].
AB  - The purpose of this study was to assess the diaphragmatic excursion using the TM
      mode ultrasonography with concomitant pneumotachography in eight normal and five
      asthmatic subjects before and after salbutamol. We report the results in normal
      and asthmatic patients of this procedure. Particular findings were demonstrated
      in asthma. Different significant correlations were found between sonographic and
      respiratory measurements. In view of the safety of this direct and real-time
      diaphragmatic investigation, we conclude that this new method could offer an
      effective and reliable procedure in the evaluation of patients with diaphragmatic
      dysfunction. However, our study was limited by the small number of patients
      included and definite conclusions should await further investigations.

PMID- 8570940
TI  - [Immunoscintigraphy in oncology].
AB  - In vivo immunotargeting of specific antigens with radiolabeled monoclonal
      antibodies is a new method of diagnosis which has largely improved over the past
      15 years. It has been especially developed in the oncologic field. Although it is
      not yet a daily procedure, immunoscintigraphy has been proven a useful diagnostic
      tool in many situations. It gives information about the presence of lesions and
      their neoplastic nature. For this reason, immunoscintigraphy appears as very
      complementary to morphological imaging and is mainly indicated when lesions have
      insufficient anatomical definition. Early detection of recurrences is actually
      the best indication of immunoscintigraphy. However, some problems still exist,
      concerning the tumor/tissues uptake ratio which is not sufficient for an optimal
      imaging contrast, and the apparition of human anti-mouse antibodies (HAMA) in the
      patients. At present, many works are in progress which could resolve these
      problems. Ultimately, well-performed clinical trials are necessary to establish
      the right place for immunoscintigraphy in the diagnostic and therapeutic
      strategies in oncology.

PMID- 8570941
TI  - [Localized muscular hypertrophy in a familial form of sarcoidosis].
AB  - Muscular hypertrophy, rarely reported in muscular sarcoidosis, is usually
      associated with the myositic, myopathic and nodular types. We report a case with
      an isolated localised muscular hypertrophy simulating a tumor formation developed
      after repetitive efforts, in a familial context of sarcoidosis. MRI shows
      muscular high intensity lesions in the thighs and calves, and after treatment,
      central areas of low intensity signal. Muscular biopsy confirms diagnosis of
      sarcoidosis. Gallium-67 scintigraphy shows systemic extension of disease. This
      case highlights the usefulness of recent imaging techniques in diagnostic
      strategy and follow up.

PMID- 8570942
TI  - [Guillain-Barre syndrome complicating cytomegalovirus infection in an
      immunocompetent adult].
AB  - Guillain-Barre syndrome is a rare complication of cytomegalovirus infection in
      the healthy adult. We report a new case with good spontaneous outcome.
      Cytomegalovirus has been recognized in about 15% of Guillain-Barre syndromes.
      Clinical and biological presentation, and outcome are common and prognosis is
      often good. Etiopathogenic mechanism is unclear.

PMID- 8570944
TI  - [Percutaneous vertebroplasty].
AB  - Vertebroplasty is a new therapeutic method which by way of filling with acrylic
      cement in the vertebral body gives a stabilization of the vertebra and an
      antalgic effect in painful lesions involving the spine. Main indications consist
      of spine angiomas, metastases and osteoporotic fractures involving the vertebral
      body. In most patients, vertebroplasty gives a very good and durable antalgic
      effect as in cases of angiomas or metastases as in post-therapeutic sequellae in
      malignant hematosarcomas. In osteoporotic fractures, antalgic effect is obtained
      very rapidly, but the follow-up is actually insufficient to evaluate the long
      term benefit.

PMID- 8570943
TI  - [Primary AL-type amyloidosis disclosed by Horton disease].
AB  - Primary systemic amyloidosis rarely affects the walls of small and medium-sized
      vessels. We report a case of primary AL amyloidosis masquerading as giant cell
      arteritis at the onset of the disease, revealed by the temporal arteritis biopsy,
      and successfully treated by corticotherapy for three years. Histology of temporal
      arteritis confirms the diagnosis of amyloidosis (characteristic birefringence
      with Congo red). We discuss in this case the diagnosis of primary amyloidosis
      revealed by Horton disease, or the coincidental association of these two
      diseases.

PMID- 8570945
TI  - [New therapeutic prospects in Alzheimer disease].
AB  - The approval for marketing of tacrine (Cognex), an acetylcholinesterase
      inhibitor, allowed physicians and the general people to attract attention to a
      degenerative disease, which prevalence dramatically increases every year. This
      drug is hopeful. Meanwhile, we must keep in mind that it has only a symptomatic
      effect. Its hepatotoxicity requires regular biological tests. Many medications
      are actually in earlier stages of development along with various etiological
      approaches.

PMID- 8570946
TI  - [A medio-protuberant hypersignal].

PMID- 8570947
TI  - [Paraneoplastic seropositive polyarthritis].

PMID- 8570948
TI  - [Pseudotumor of the external oblique muscle disclosing sarcoidosis].

PMID- 8570949
TI  - [Viral quantification: an old concept and new markers].

PMID- 8570950
TI  - [Treatment of corticodependent systemic lupus erythematosus with low-dose
      methotrexate].
AB  - The authors report an open prospective study in a group of 16 patients who
      presented systemic lupus erythematosus with cutaneous and articular symptoms, and
      who required treatment with a minimum dose of 15 mg per day of prednisone.
      Methotrexate was given at a dose of 7.5 mg IM per week. Efficacy was demonstrated
      at the third month with a statistical analysis of four evolution parameters.
      Improvement was observed in 13 patients out of 16 and permitted the reduction of
      the amount of prednisone required. Secondary relapse occurred in four cases in
      spite of an increase in the dose of methotrexate (10 mg per week). Minor side
      effects were observed in four cases, and methotrexate was discontinued in only
      two cases. This study suggests that treatment by low doses of methotrexate is
      beneficial to patients with articular and cutaneous manifestations of
      corticodependent systemic lupus erythematosus and this therapy could be
      corticosteroid-sparing.

PMID- 8570951
TI  - [Osteoporotic vertebral crush fractures with severe neurologic manifestations.
      Apropos of 6 cases].
AB  - Osteoporotic vertebral crush fractures with neurologic complications are rarely
      reported in the literature. We report six new cases particularly severe in which
      death occurred in two cases. The study group included four women and two men with
      a mean age of 75 years (range: 72-79). Vertebral collapse causing neurological
      deficit was T5, T9, T11 in two cases, L1 and L3. The mean number of vertebral
      collapses was three per patient (range: 1-9). Back pain appeared without
      traumatism 6 weeks before admission (range: 1-24). Neurological complications
      appeared 2.5 weeks after back pain (range: 1-8). One patient suffered from a
      paraplegia, three from a paraparesia with bladder dysfunction (n = 1). In one
      case there was a severe weakness of the levator muscles of the foot and in
      another a L3 femoral neuralgia with severe bowel and bladder dysfunction. X-rays
      demonstrated backwards displacement of the posterior cortex in three cases, an
      intravertebral vacuum phenomenon in two cases and a heterogeneous appearance
      suggesting a malignancy in two cases. Computed tomography, performed in four
      patients and tomography in one patient, demonstrated fragmentation of the
      vertebral body in all the cases and vacuum phenomenon in four cases. Magnetic
      resonance imaging performed in four cases has confirmed the absence of epiduritis
      and a compression due to bony structures in two cases. A vertebral biopsy was
      performed in three cases. Osteoporosis was observed in all the cases and in two
      cases there was also an osteonecrosis. Surgical treatment was performed in three
      cases and conservative medical treatment in the other cases. After surgical
      treatment we have observed an absence of improvement of neurological
      complications in one case, an improvement in another and finally a full recovery
      in the last case. After conservative treatment we have noted in two cases an
      absence of improvement of neurological complications and in one case an
      improvement of neurological deficit. Two patients died (one after medical
      treatment and another after surgical treatment).

PMID- 8570952
TI  - [Systemic diseases in myelodysplastic syndromes].
AB  - Myelodysplastic syndromes (MDS) are characterized by quantitative and functional
      involvement of myeloid lineages. Yet, systemic manifestations, suggestive of a
      lymphocytic involvement, have been described in MDS. We review here biological
      and clinical data concerning the associations between MDS and immunological
      disorders. Biological auto-immune markers are in fact rare in MDS, and especially
      encountered in the chronic myelomonocytic leukemia subgroup. Only a few systemic
      diseases seem to be frequently associated with MDS: seronegative arthritis,
      cutaneous vasculitis, and relapsing polychondritis. These diseases are probably
      not entirely auto-immune, and the signification of their association with an MDS
      remains unclear. About 30% of relapsing polychondritis are associated with MDS.
      Conversely, 0.6% of MDS are associated with a relapsing polychondritis. These
      associations are mainly encountered in men suffering from a refractory anemia
      (with or without excess of blasts). The main cytogenetic abnormalities are
      monosomy 7, presence of a ring chromosome, and monosomy 16.

PMID- 8570953
TI  - [Human parvovirus B19 infection. Update].
AB  - Pathogenicity of parvovirus B19 has been demonstrated. The spectrum of clinical
      manifestations varies according to the age and immune status of affected
      patients. Parvovirus B19 is the aetiologic agent of erythema infectiosum in
      children. In normal adults, it is responsible for acute, bilateral and
      symmetrical arthritis, although chronic arthritis can develop. Parvovirus B19 has
      a particular tropism for erythroid precursors: in patients with underlying
      hemolysis, it induces transient aplastic crisis; in immunosuppressed patients the
      virus can lead to chronic pure red cell aplasia. Hydrops fetalis is one of the
      most severe manifestation of the infection. Diagnosis of recent parvovirus B19
      infection is based upon serology and PCR, especially in immunosuppressed patients
      in whom polyvalent intravenous immunoglobulins must be started. The link between
      parvovirus B19 and systemic vasculitis is questioned.

PMID- 8570954
TI  - [Ki-1 positive non-Hodgkin's lymphoma disclosed by mucocutaneous ulcerations and
      glomerulonephritis].
AB  - Malignant lymphoma particularly of T phenotype can be associated with specific or
      non specific cutaneous lesions. These cutaneous manifestations can occur at the
      onset of the disease being sometimes the revealing sign or they can appear during
      the course of the lymphoreticular malignancies. Glomerulonephritis was also
      described in lymphoma. Ki-1 positive large cell lymphoma was recently identified.
      A new case is reported with lymphadenopathy and intestinal localisation revealed
      by cutaneous and mucosal ulcerations principally in the mouth and a focal
      segmental glomerulonephritis with endo- and extracapillary proliferation. The
      absence of lymphoma in cutaneous and renal lesions and the clinical presentation
      support the hypothesis of paraneoplastic manifestations, may be related to a
      vasculitis.

PMID- 8570955
TI  - [Sweet syndrome and Yersinia enterocolitica infection. 2 cases].
AB  - Sweet's syndrome is an acute febrile neutrophilic dermatosis. Although it
      frequently appears as an idiopathic disorder, it may occur in association, often
      as presenting sign, with malignancy or more rarely with infections. We report two
      cases of Sweet's syndrome preceded by digestive infection due to Yersinia
      enterocolitica, affirmed by significant rises in serum antibody titers. Other
      nongastrointestinal manifestations of such infections are known, predominantly
      arthritis and erythema nodosum. Sweet's syndrome is a rare complication of these
      infections. Treatment with systemic steroids, usually effective, can be replaced
      by antibiotics with apparently favorable results. The search of an infectious
      origin should be systematic in cases of Sweet's syndrome that appear to be
      idiopathic.

PMID- 8570956
TI  - [Association of mycosis fungoides and Jaccoud syndrome].
AB  - We report here a case of a 49 year-old woman who developed a unilateral Jaccoud's
      arthropathy 9 years after a mycosis fungoides of the left hand. This rheumatic
      affection, described in 1866, is a deformation of the hands or of the feet linked
      to a periarticular disease without any bone lesion. Many causes have been
      registered but the most frequent etiology is the systemic lupus erythematosus.
      The mycosis fungoides had never been reported as yet to be responsible to the
      Jaccoud's arthropathy.

PMID- 8570957
TI  - [Cutaneous ulcerations in sarcoidosis].
AB  - We report the case of a 23 year-old Caribbean woman with sarcoidosis who
      developed specific skin ulcerations. Ulcerative lesions in sarcoidosis are
      distinctly unusual, generally multiple, painless, with preponderant location on
      the lower limbs. The diagnosis is difficult. The pathogenesis is discussed. The
      most successful therapy is hydrochloroquine with corticosteroids.

PMID- 8570958
TI  - [Sweet syndrome associated with Crohn disease].
AB  - The association of Sweet's syndrome and Crohn's disease is rare. We report a new
      case of such association. A 45 year-old woman developed a diarrhea, fever, and
      skin lesions consistent with a presumptive diagnosis of Sweet's syndrome. Crohn's
      disease was also diagnosed. Oral prednisone, associated with mesalazine, effected
      improvement of both cutaneous lesions and bowel disease. The ten cases of the
      literature and ours show that Sweet's syndrome may occur during an acute phase of
      Crohn's disease. Most of the time, Crohn's disease has already been diagnosed.
      However, this was not so with our patient, wherein lies the originality of our
      case. A general corticotherapy is the preferred course of treatment.

PMID- 8570959
TI  - [Nervous microangiopathy and POEMS syndrome].
AB  - The authors report the case of a 40 year-old man with POEMS syndrome (peripheral
      neuropathy, organomegaly, endocrinopathy, M-protein and skin changes).
      Pathological studies of the peroneal nerve showed a microangiopathy of the vasa
      nervorum. Several authors have already reported microvascular abnormalities that
      could be responsible for some systemic manifestations of the POEMS syndrome,
      involving the skin, the kidney and the peripheral nerves. This new case enhances
      this hypothesis. The relation between microangiopathy and plasma cell dyscrasia
      is unknown.

PMID- 8570960
TI  - [Paraneoplastic pemphigus: review of the literature, apropos of a case associated
      with chronic lymphoid leukemia].
AB  - In 1990, Anhalt et al described a newly autoimmune bullous disease:
      paraneoplastic pemphigus, in five patients. It was characterized by a distinct
      set of circulating autoantibodies from those in the sera of patients with
      pemphigus vulgaris and superficial pemphigus. We report a 71 year-old man with
      chronic lymphocytic leukemia of 4 years duration who developed a severe
      mucocutaneous eruption with clinical and immunofluorescence findings of pemphigus
      vulgaris evolving into an oral bullous lichen planus presentation. Evaluation of
      his serum confirmed the presence of autoantibodies specific for paraneoplastic
      pemphigus by indirect immunofluorescence on rat-bladder and immunoprecipitation.
      Subsequently, additional cases have been reported in the literature. All occurred
      in patients with various neoplastic conditions. These patients present with
      polymorphous skin lesions and severe erosive oral disease. Histologic examination
      shows interface dermatitis and keratinocyte necrosis in addition to acantolysis.
      Direct immunofluorescence may reveal deposition of immunoglobulin and/or
      complement at the basement membrane as well as deposition on epithelial cell
      surfaces. Circulating IgG anti-cell-surface antibodies are detectable with both
      stratified and stratified epithelia as substrates. These antibodies
      immunoprecipitate a complex of four desmosomal proteins, including desmoplakin I
      (250 kDa), the bullous pemphigoid antigen (230 kDa), desmoplakin II (210 kDa) and
      a 190 kDa antigen.

PMID- 8570961
TI  - [Hormone replacement therapy in menopause and cancers].
AB  - The long term outcome analysis of estrogen replacement therapy shows that the
      carcinologic risk is far more inferior than the osseous and cardiovascular risks
      of which the prevention is ensured by estrogen. In the same way, the quality of
      life improvement during the years following menopause is important. For a female
      population without personal risk of breast cancer, the substitutive hormone
      therapy offers numerous advantages which have been for a long time refused to
      women with previously treated breast cancer. Any dogmatic behaviour is presently
      justified. On the contrary, the hormonal replacement therapy requires beforehand
      an analysis as exact as possible of the risks of its prescription as of its non
      prescription and a responsibility taking shared between the physician and his
      patient. The progresses of the molecular biology and the expansion of randomized
      trials will permit with no doubt to recognize more easily for each patient, even
      the one who would have been previously treated for a breast cancer, the
      respective impact of carcinologic, cardiovascular and osseous risks.

PMID- 8570962
TI  - [Therapeutic principles in gastroesophageal reflux].
AB  - Gastroesophageal reflux is a common disease. Its chronic course, even if mild, is
      sometimes complicated by erosive oesophagitis. Drug therapy acts against gastric
      acidity and motility disorders. Treatment of gastroesophageal reflux disease has
      three aims: improvement of symptoms and quality of life, healing erosive lesions
      and prevention of symptomatic and endoscopic relapses. Non-drug measures are
      always useful, even if their efficacy is not well established. Initial therapy of
      a symptomatic reflux or mild oesophagitis is most of the time effective
      (antacids, prokinetics, H2 receptor antagonists). Proton-pump inhibitors are also
      effective in healing and preventing severe oesophagitis. Questions about long
      term treatment adverse events with powerful acid inhibitors, such as
      hypergastrinemia and the risk of gastric carcinoid tumours seem to be resolved.
      Studies are requested to define the optimal long-term maintenance treatment with
      cisapride, H2 receptor antagonists or proton-pump inhibitors at low doses in
      prevention of symptomatic and mild oesophagitis relapses.

PMID- 8570963
TI  - [Severe polychondritis].

PMID- 8570964
TI  - [Retrobulbar optic neuritis caused by disulfiram (Esperal): a case].

PMID- 8570965
TI  - [Prolonged fever induced by fluindione].

PMID- 8570966
TI  - [Neurologic manifestation of Horton disease. Value of heparin therapy].

PMID- 8570967
TI  - [New methods of quantification of the viral load in HIV infection].

PMID- 8570968
TI  - [Immunopathological mechanisms of HIV infection].

PMID- 8570969
TI  - [Immunomodulator treatments in HIV infection: rational bases and therapeutic
      prospects].

PMID- 8570970
TI  - [Prevention of opportunistic infections in HIV infection].

PMID- 8570971
TI  - [Drug-induced photodermatoses: how are they to be diagnosed and interpreted?].

PMID- 8570972
TI  - [Lupus and sunlight].

PMID- 8570973
TI  - [Cutaneous photocarcinogenesis].

PMID- 8570974
TI  - [Light-induced eruptions and their photoprotection].

PMID- 8570976
TI  - The contrary ideals of individualism and nursing value of care.
AB  - Despite the relational worldview that underpins nursing caring, the cultural
      value of individualism remains firmly embedded in nursing's conceptual systems.
      Individualism forms the basis of notions such as autonomy, self-reliance,
      personal rights and entitlement. When nurses concomitantly espouse the value of
      care, an orientation that stands in contrast to the predominant societal motif of
      the autonomous individual, they find themselves having to reconcile contrary
      ideals. The significance of the coexistence of the values of individualism and
      care rests upon the capability of each to contrast and sharpen our understanding
      of the other. The convergent outcome is the empowerment of nurses to refine their
      understanding of the human condition in illness and health, and to articulate a
      public practice of care that would temper the fundamental mark of nointerference
      in the traditional notion of individualism in American culture.

PMID- 8570975
TI  - Family caregiver role acquisition: role-making through situated interaction.
AB  - Family caregiver role acquisition is an important, but little studied phenomenon.
      In this article, a conceptual approach for research on caregiver role acquisition
      is suggested. Caregiver role acquisition is defined as a family role transition.
      During this transition, the caregiving role is created through interaction
      between the caregiver and care receiver and between the dyad and others. Thus,
      caregiver role acquisition is a role-making process. An approach to social roles
      that integrates symbolic interactionism and structural role theory suggests that
      the role-making processes inherent in caregiver role acquisition occur through
      situated interaction. Concepts are identified from interactionist and structural
      perspectives that account for variation in individual experience with role
      acquisition. Indicators of health during caregiver role acquisition are also
      identified. Included are subjective indicators (role strain and role
      satisfaction), behavioral indicators (role insufficiency and role mastery), and
      interpersonal indicators (family conflict and mutuality).

PMID- 8570977
TI  - The effects of waterbeds on heart rate in preterm infants.
AB  - The purpose of this study was to investigate the effects of waterbeds on heart
      rate (HR) in preterm infants. Subjects were 22 medically stable preterm infants.
      Across a 10-day study, HR was determined for a 1-hour period on each day.
      Baseline HRs with infants on the standard incubator mattress were obtained on the
      first 2 days of the study. They were then placed on the waterbed for 4 days. They
      were then returned to the incubator mattress and studied for 4 more days. Infants
      served as their own controls among baseline, on-waterbed (On-WB) and off-waterbed
      (Off-WB) periods. HR was determined by using a heart beat counting feature of the
      neonatal cardio-respiratory monitors. Analysis of variance revealed significant
      HR variability among subjects. There was no difference between baseline HR and on
      waterbed HR. The HR increased when infants were transferred back to the standard
      mattress. The possibility that theophylline acted as a confound existed because
      doses were changed and levels varied for some subjects within the study period.
      Eight infants responded to the waterbed with lower HR during the On-WB period
      compared to the baseline (mean reduction = 5.7 bpm). The findings that HRs rose
      when the infants were returned to the incubator mattress are similar to those of
      a previous study. The subjects' reactivity to changes in treatment condition
      continues to confound the question as to whether waterbed therapy effects a
      reduction in HR. Since waterbeds have consistently resulted in soothing effects
      such as improved sleep and lowered activity, failure to produce a concomitant
      reduction in HR warrants attention toward other factors that may be determinants
      of heart rate. The high variability within and among subjects raises questions as
      to the usefulness of the HR variable for determining energy costs.

PMID- 8570978
TI  - An exploration of an innovative methodological approach for examining nurses'
      heuristic use in clinical practice.
AB  - What heuristics (reasoning strategies) do experienced critical care nurses use to
      assist in reasoning and making decisions about patient care? In this study, think
      aloud data were collected and protocol analysis was utilized to identify and
      describe the heuristics that permitted nurses to evaluate patient data, assess
      patient status, and make decisions necessary to maintain patient stability. Five
      heuristics were identified: pattern recognition, attending, anchoring, focused
      questioning, and listing. Clearer understanding of nurses' heuristic use could
      improve reasoning in practice, and could also provide educators with strategies
      to enhance the reasoning of their students.

PMID- 8570979
TI  - [Cholestatic hepatitis and amoxicillin-clavulanic acid combination. Personnel
      case report and literature review].
AB  - The association amoxicillin-clavulanic acid is a widely used medication. Only
      about 15 cases of cholestatic hepatitis were reported in Belgium between 1990 and
      1993; about 100 cases have been reported to the pharmaceutical company. This
      effect is severe but reversible. The injury is probably idiosyncratic or
      immunologically based. Age, sex and treatment duration are as many agents of
      risk. The diagnosis is undertaken on basis of clinical examination, chronological
      study, biological evolution and histology.

PMID- 8570980
TI  - [Male breast cancer].
AB  - From 1974 till 1993, 9 patients have been treated in our Hospital for a breast
      cancer. Compared with the amount of women breast cancers treated, actually near
      300 per year, this 0.3% figure seems small, and is lower than that found in the
      literature (1%). The therapeutic attitude is the same as that proposed for women.
      The follow-up varied from 9 to 120 months with a mean of 57. Five patients are
      actually still living without recurrence. One patient presented a local
      recurrence, one was lost sight off and two died from their cancer. Despite the
      fact that it was a small group of patients we can say that the symptoms, the
      clinical staging, the proposed treatments and the survival rate are the same as
      found in the literature.

PMID- 8570981
TI  - [Enlargement of the upper mediastinum in thoracic radiography?].
AB  - The authors report a case of asymptomatic sternocostoclavicular hyperostosis in a
      69-year-old patient. SAPHO syndrome is described and discussed.

PMID- 8570982
TI  - [Positron-emission tomography in akinetic rigidity syndrome].
AB  - Positron emission tomography (PET) is applied to the metabolic evaluation of
      hypokinetic disorders and particularly to the study of Parkinson's disease. PET
      has proved useful for a better understanding of the pathophysiology of these
      disorders. Several types of tracers are used for these studies: pre- and post
      synaptic markers of the dopaminergic synapse and markers of the global metabolism
      of brain structures involved in the control of movement. The latter can be used
      at rest or in states of motor activation. These PET tracers have been used to
      test hypotheses on the aetiology and evolution of Parkinson's disease and on the
      pathophysiology of drug-induced side effects. PET also allows quantitative
      evaluation of new treatment strategies including experimental approaches such as
      intra-cerebral transplantation.

PMID- 8570983
TI  - [Genetic mechanism of human sex differentiation].
AB  - The genetic mechanism controlling sexual differentiation had remained unknown for
      a long time. Karyotype analysis of sex-inverted patients or individuals with
      ambiguous sexual differentiation has enabled the localization and identification
      of genes involved. It is currently known that the SRY gene is responsible for the
      initiation of a cascade reaction leading to male differentiation of the primitive
      gonad. SRY is a +/- 820 base pairs gene located on the small arm of the Y
      chromosome, more precisely within the 1A1 alpha sub-segment. Although a few other
      genes are known to be involved in the downstream regulation of SRY, their precise
      mode of action is yet unknown.

PMID- 8570984
TI  - [Additional education of pharmacy students in clinical care units: a useful
      experience?].
AB  - Following the French program of pharmaceutical education, students of the
      Pharmaceutical Institute of the Universite Libre de Bruxelles have taken, during
      six weeks, an additional training in a department of internal medicine of three
      university hospitals. The results of this experience show that this program
      modification, particularly if it is carefully prepared, is highly advantageous
      for the pharmacist education. Moreover, it may consolidate the collaboration
      between the pharmacist with the medical profession and therefore represent a
      contribution to Health Care.

PMID- 8570985
TI  - [Emergency measures in accidental exposure to ionizing radiation].
AB  - The present paper is intended to provide any physician with a basic information
      and recommendations on how to behave with individuals who have been irradiated
      and/or contaminated (or believed to have been exposed), either in the case of a
      broad nuclear accident or a limited accidental exposure (e.g. occupational).
      Emphasis is put on the emergency measures to be taken as well as on their
      relative priority. Information is also provided in order to allow any physician
      to assess the magnitude and the severity of the exposure on the basis of early
      clinical symptoms and reactions. This would enable him to sort out the patients
      and to orientate them towards the appropriate specialized centre, or on the other
      hand, to reassure the patients. The information and recommendations are
      presented, purposely, in a concise and schematic way in order to facilitate, when
      needed, a quick and easy reading.

PMID- 8570986
TI  - [Pharma-clinics. How I treat... anemia (3)].

PMID- 8570987
TI  - [Clinical case of the month. Value of a pentagastrin test in the early detection
      of thyroid medullary cancer].

PMID- 8570988
TI  - [Current knowledge in the treatment of chronic hepatitis C].

PMID- 8570989
TI  - [Use of current anti-arrhythmia agents in pediatric cardiology].

PMID- 8570990
TI  - [Bone scintigraphy and algodystrophy].

PMID- 8570991
TI  - [Role of the general physician in a screening strategy for cancer of the cervix
      uteri].

PMID- 8570992
TI  - [Screening for and early diagnosis of cutaneous melanoma].

PMID- 8570993
TI  - [Suicide in Belgium: current statistics].

PMID- 8570994
TI  - [Medicolegal aspects of occupational deafness].

PMID- 8570995
TI  - [How I diagnose... anorexia nervosa].

PMID- 8570996
TI  - [Pharma-clinics. Drug of the month. Terazosine (Hytrin)].

PMID- 8570997
TI  - Applied physiology of rugby league.
AB  - Rugby League is a game of physical contact that involves low-intensity, aerobic
      exercise, combined with periods of intermittent, intensive anaerobic exercise.
      Matches consist of two halves, each of 40 minutes, separated by a 10-minute
      recovery period, and are contested by 2 teams of 13 players (6 forwards and 7
      backs). Whilst the amount of time spent by individual players on low-intensity
      exercise exceeds the duration of high-intensity exercise, the nature of the high
      intensity efforts (involving sprinting, lower- and upper-body impacts and high
      force generation) is such that the overall intensity of the game is greatly
      increased. Individual players have been shown to cover distances of approximately
      5000 to 8000m a game, and be involved in 20 to 40 tackles. Maximum oxygen uptake
      (VO2max) values of around 56 ml/kg/min have been reported for rugby league
      players, with no differences between the values of forwards and backs. Forwards
      have, however, been shown to generally have higher body mass, subcutaneous fat
      and fat-free mass levels than backs. Backs have been found to be quicker than
      forwards and produce greater leg power output when related to fat-free mass. The
      amount of physiological data on rugby league players and the sport of rugby
      league is very limited, and there is considerable scope for future research in
      this area.

PMID- 8570998
TI  - Friction blisters. Pathophysiology, prevention and treatment.
AB  - Blisters occur frequently, especially in vigorously active populations. Studies
      using respective rubbing techniques show that blisters result from frictional
      forces that mechanically separate epidermal cells at level of the stratum
      spinosum. Hydrostatic pressure causes the area of the separation to fill with a
      fluid that is similar in composition to plasma but has a lower protein level.
      About 6 hours after formation of the blister, cells in the blister base begin to
      take amino acids and nucleosides; at 24 hours, there is high mitotic activity in
      the basal cells; at 48 and 120 hours, new stratum granulosum and stratum corneum,
      respectively, can be seen. The magnitude of frictional forces (Ff) and the number
      of times that an object cycles across the skin determine the probability of
      blister development - the higher the Ff, the fewer the cycles necessary to
      produce a blister. Moist skin increases Ff, but very dry or very wet skin
      necessary to produce a blister. Moist skin increases Ff, but very dry or very wet
      skin decreases Ff. Blisters are more likely in skin areas that have a thick horny
      layer held tightly to underlying structures (e.g. palms of the hands or soles of
      the feet). More vigorous activity and the carrying of heavy loads during
      locomotion both appear to increase the likelihood of foot blisters.
      Antiperspirants with emollients and drying powders applied to the foot do not
      appear to decrease the probability of friction blisters. There is some evidence
      that foot blister incidence can be reduced by closed cell neoprene insoles.
      Wearing foot socks composed of acrylic results in fewer foot blisters in runners.
      A thin polyester sock, combined with a thick wool or polypropylene sock that
      maintains its bulk when exposed to sweat and compression reduces blister
      incidence in Marine recruits. Recent exposure of the skin to repeated low
      intensity Ff results in a number of adaptations including cellular proliferation
      and epidermal thickening, which may reduce the likelihood of blisters. More well
      designed studies are necessary to determine which prevention strategies actually
      decrease blister probability. Clinical experience suggests draining intact
      blisters and maintaining the blister roof results in the least patient discomfort
      and may reduce the possibility of secondary infection. Treating deroofed blisters
      with hydrocolloid dressings provides pain relief and may allow patients to
      continue physical activity if necessary. There is no evidence that antibiotics
      influence blister healing. Clinical trials are needed to determine the efficacy
      of various blister treatment methods.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8570999
TI  - Medicine and mechanisms in altitude sickness. Recommendations.
AB  - Acute mountain sickness (AMS) has long been recognised as a potentially life
      threatening condition afflicting otherwise healthy normal individuals who ascend
      rapidly to high altitude where the partial pressure of oxygen (pO2) in the air is
      reduce. The symptoms of AMS (e.g. headache, poor appetite and nausea, fatigue and
      weakness, dizziness or light-headedness and poor sleep) are probably a
      consequence of disturbances in fluid balance brought about by severe tissue
      hypoxia. AMS can be prevented by an adequately slow ascent, which is the best
      method, but for those with limited time there are several drug therapies that
      provide a relatively good protection. Acetazolamide (250 mg twice daily or 500 mg
      slow release once daily), taken before and during, ascent is probably the
      treatment of choice; it improves gas exchange and exercise performance and
      reduces the symptoms of AMS in most individuals. Dexamethasone (4 mg, 4 times
      daily) is more of value for short term treatment or prevention, and should never
      be used for more than 2 to 3 days. Prophylactic use of progesterone looks
      promising, but more studies are required.

PMID- 8571000
TI  - Exercise and brain neurotransmission.
AB  - Physical exercise influences the central dopaminergic, noradrenergic and
      serotonergic systems. A number of studies have examined brain noradrenaline
      (norepinephrine), serotonin (5-hydroxytryptamine; 5-HT) and dopamine with
      exercise. Although there are great discrepancies in experimental protocols, the
      results indicate that there is evidence in favour of changes in synthesis and
      metabolism of monoamines during exercise. There is a possibility that the
      interactions between brain neurotransmitters and their specific receptors could
      play a role in the onset of fatigue during prolonged exercise. The data on the
      effects of branched chain amino acid (BCAA) supplementation and 'central fatigue'
      seem to be conflicting, although recent studies suggest that BCAA supplementation
      has no influence on endurance performance. There are numerous levels at which
      central neurotransmitters can affect motor behaviour; from sensory perception,
      and sensory-motor integration, to motor effector mechanisms. However, the crucial
      point is whether or not the changes in neurotransmitter levels trigger or reflect
      changes in monoamine release. Until recently most studies were done on
      homogenised tissue, which gives no indication of the dynamic release of
      neurotransmitters in the extracellular space of living organisms. Recently, new
      techniques such as microdialysis are voltammetry were introduced to measure in
      vivo release of neurotransmitters. Microdialysis can collect virtually any
      substance from the brain of a freely moving animal with a limited amount of
      tissue trauma. This method allows measurement of local neurotransmitter release
      during on-going behavioural changes such as exercise. The results of the first
      studies using these methods indicate that the release of most neurotransmitters
      is influenced by exercise. Although the few studies that have been published to
      date show some discrepancies, we feel that these recently developed and more
      sophisticated in vivo methods will improve our insight into the relationship
      between the monoamine and other transmitters during exercise. Continued
      quantitative and qualitative research needs to be conducted so that a further
      understanding of the effects of exercise on brain neurotransmission can be
      gained.

PMID- 8571001
TI  - Thyroid status and exercise tolerance. Cardiovascular and metabolic
      considerations.
AB  - Both hypo- and hyperthyroidism are characterised by exercise intolerance. In
      hypothyroidism, inadequate cardiovascular support appears to be the principal
      factor involved. Insufficient skeletal muscle blood flow compromises exercise
      capacity via reduced oxygen delivery, and endurance through decreased delivery of
      blood-borne substrates. The latter effect results in increased dependence on
      intramuscular glycogen. Additionally, decreased mobilisation of free fatty acids
      from adipose tissue and, consequently, lower plasma free fatty acid levels
      compound the problem of reduced lipid delivery to active skeletal muscle in the
      hypothyroid state. In contrast, cardiovascular support is enhanced in
      hyperthyroidism, implicating other factors in exercise tolerance. Greater
      reliance on muscle glycogen appears to be the primary reason for decreased
      endurance. Biochemical changes with hyperthyroidism that would favour enhanced
      flux through glycolysis may account for this dependence on glycogen. Deviations
      from normal thyroid function, and the ensuing exercise tolerance, require
      appropriate medical therapy to attain euthyroid status.

PMID- 8571002
TI  - Rock climbing injuries.
AB  - Rock climbing has become increasingly popular in the past decade. However, the
      increased participation exposes a greater number of climbers to potential injury.
      The risks involved with climbing increase in proportion to the skill-level of the
      climber: the higher the skill-level, the more hours are required for training and
      on more difficult routes. The hands are used as tools for the ascent, with much
      of the climber's weight placed upon the fingers and also distributed through the
      wrist, elbow and shoulders. The combination of repetitive climbing and the
      excessive weight-bearing demands of the sport result in cumulative trauma to the
      upper limbs. Prevention should begin with educating climbers on the potential
      risk for injury. Although adequate rest between climbs and decreased training
      when pain is first encountered would aid in alleviating numerous problems,
      additional search directed towards improving training, treatment and
      rehabilitation programmes is warranted.

PMID- 8571003
TI  - Use of knee braces in sport. Current recommendations.
AB  - This article provides a review of the progress that has been made on the
      biomechanical, functional performance and epidemiological investigations into the
      effectiveness of prophylactic knee braces (PKBs) since the position statement
      against their use was issued in 1987 by the American Academy of Orthopaedics and
      a review of this subject was last published in Sports Medicine in 1989 by
      Montgomery and Korziris. The evolution of the salient design features of three
      surrogate knee models are reviewed along with the results of PKB effectiveness
      and safety factor testing. While still too limited in scope to be totally
      realistic, major advances have been made in the sophistication of the present
      biomechanics laboratory testing conditions. The on-the-field functional
      performance effects of wearing a knee brace are not always manifest in all
      individuals. The efficacy of PKBs remains in question but recent studies have
      taught us enough to put their use into perspective. While they may play some
      role, PKBs probably represent the least important factor in influencing the
      likelihood that a medial collateral ligament (MCL) sprain will occur. On the
      other hand, there is no evidence that such braces put added valgus pressure on
      some knees, or that wearing a brace is associated with an increased frequency or
      severity of knee or ankle injury. All else being equal, from the biomechanical
      studies, we know that whilst some braces are better than others, currently
      available PKBs can provide 20 to 30% greater resistance to a lateral blow, with
      the possibility that the anterior cruciate ligament (ACL) is given even greater
      protection than the MCL. This appears to be true when the lateral blow is of
      sufficient magnitude to cause significant medial joint line opening, but is not
      as great at the very lowest levels of impact. Regardless of the material they are
      made of, the most effective PKBs are those sufficiently stiff to prevent an
      external blow at the joint line from causing brace hinge contact with the knee
      tissues. Based on the superior results of the custom-fit functional braces, the
      most important future design feature appears to be the sizing and fitting of the
      thigh and tibial cuffs. On the negative side, the presence of a brace may slow an
      athlete's straight-ahead sprint speed and cause early fatigue to its wearer. This
      effect appears to vary from one brace to another according to its weight, design
      features, and pressure from the leg and thigh straps. However, it appears that
      knee braces do have the potential to restrict performance of the athlete for high
      speed running but the effect is related to several factors. The weight of the
      brace resultant friction of the hinges, completeness of fit, and tightness of
      straps appear to be important. The most measurable effects include: increased
      muscular relaxation pressures; increased energy expenditure; and a related
      increase in blood lactate levels, maximal torque output, oxygen consumption and
      heart rate. On the other hand, experienced brace wearers and larger, stronger
      individuals displayed fewer, or no effects of donning a brace. Improvements in
      the protectiveness of the PKB are likely to accompany improvements in the ability
      to contour the braces to fit each individual's leg in the equipment room without
      the added expense of the cast-moulding process. Further improvement may be
      realised by friction-free polycentric joints, as well as an attachment system
      that minimises thigh and calf soft tissue compression perhaps by incorporating
      the braces into the trousers of the uniform to provide suspension from the waist.

PMID- 8571005
TI  - Monitoring overtraining in athletes. Recommendations.

PMID- 8571004
TI  - Flow cytometry. Principles and applications in exercise immunology.

PMID- 8571006
TI  - Influence of time of day on psychological responses to exercise. A review.
AB  - Circadian rhythms have been documented for various physiological variables, such
      as body temperature, heart rate, blood pressure, cortisol, adrenaline
      (epinephrine) and noradrenaline (norepinephrine) under resting, as well as
      exercise conditions. The extent to which psychological variables, such as
      perception of effort, mood states and anxiety, are subject to circadian rhythms
      at rest and during exercise, is not as well understood. Body temperature follows
      a circadian rhythm in which temperature is highest in the evening and lowest in
      the early morning. Exercise heart rate follows a similar rhythm, but peaks a
      little earlier. The findings for exercise blood pressure are not consistent.
      Performance of physical activity is generally improved in the afternoon or
      evening, compared with morning. Cortisol levels follow a circadian rhythm in
      which cortisol peaks in the morning and decreases throughout the rest of the day,
      at rest and during exercise. Plasma catecholamines show a rhythm at rest, but the
      findings during exercise are inconsistent. Research on circadian rhythms of
      perceived exertion and mood states are equivocal and the limited research on
      anxiety suggests that the anxiolytic response to exercise is not influenced by
      time of day.

PMID- 8571009
TI  - [What is your diagnosis? Suspected 3-vessel coronary disease (main trunk
      equivalent)].

PMID- 8571007
TI  - Rehabilitation following arthroscopic meniscectomy.
AB  - Meniscal injuries are reported to be the most common injury sustained by
      athletes, with sports injuries being responsible for over 30% of the total number
      of lesions. Treatment of meniscal lesions has evolved considerably over the past
      20 years and partial meniscectomies, or menisci repairs, are now the treatment of
      choice for the majority of lesions. Following arthroscopic meniscectomy, patients
      are routinely able to walk without support within 1 to 3 days, return to work
      after 1 to 2 weeks, resume athletic training by 2 to 4 weeks and return to
      competition in 3 to 4 weeks. Physiotherapy has been widely prescribed following
      arthroscopic meniscectomy and exercise protocols have been described in the
      literature. However, few studies have actually ascertained whether or not
      physiotherapy accelerates recovery. From these studies, there is little doubt
      that some form of rehabilitation, e.g. pain control or exercises, may be
      effective in accelerating the recovery of muscle strength to preoperative values.
      Therefore, whether or not physiotherapy is required following arthroscopic
      meniscectomy may depend on the presence or absence of preoperative strength
      deficits, and thus, on whether it is the dominant or nondominant leg that is
      injured. In patients with no preoperative deficits, and a normal post-surgery
      evolution, full recovery may be expected within 6 weeks if pain and swelling are
      brought under control. Physiotherapy intervention may not, perhaps, be justified
      for these patients, except in professional athletes where a faster return to
      preoperative values may be desired.

PMID- 8571010
TI  - [The 4-S study--a turning point in the cholesterol debate. Work Group Lipids and
      Atherosclerosis of the Swiss Society for Cardiology].

PMID- 8571011
TI  - [Is there a scientific alternative to alternative medicine?].
AB  - Despite the great progress which has been made in mainstream medicine,
      alternative medicine has become increasingly attractive. Alternative medicine
      seemingly encompasses psychic and social factors, it is supposedly holistic, but
      in fact it is mechanistic and reductionistic. It's attraction is based on the
      helplessness and the hopelessness of the patient and his physician, making them
      prone to cling to the magic power of alternative medicine theories. Mainstream
      medicine has supported the boom of alternative medicine by neglecting
      psychosocial factors, i.e. the doctor-patient relationship. If mainstream
      medicine integrates the doctor-patient relationship and studies it
      scientifically, its model will change from a biomedical to a biopsychosocial one,
      thus satisfying many of the patient's needs, which were so far neglected. The
      scientific alternative to alternative medicine is biopsychosocial medicine, which
      includes biomedicine as one of its three components.

PMID- 8571008
TI  - Fatal cycling injuries.
AB  - Cycling accidents are responsible for significant morbidity and mortality,
      especially in boys under the age of 16. While most cycling injuries result from
      simple falls from the bicycle, the majority of fatalities are caused by head
      injuries resulting from accidents involving motor vehicles. It is estimated that
      up to 85% of all cycling fatalities caused by head injuries could be prevented by
      the use of an appropriate cycling helmet. Although the majority of adult cyclists
      wear helmets the reverse is true for children, who comprise the greatest
      proportion of all cyclists. Intensive educational programmes increase the number
      of cycling helmets that are sold, but have a lesser effect on the number used
      while cycling. Legislation, compassionately enforced on minors, i.e. with an
      understanding attitude towards their developmental stage, is the only proven
      technique that substantially improves rates of helmet use by young cyclists. Such
      legislation reduces their morbidity and mortality from head injuries. This
      article reviews the epidemiological factors associated with traumatic cycling
      injuries and the nature of these injuries. Special attention is paid to head
      injuries and the evidence that these are largely preventable with the use of
      appropriate 3-layered cycling helmets, the features of which are detailed.
      Factors promoting or discouraging helmet use by children are reviewed. These
      include the following factors: age, since helmet use is highest in mature
      cyclists and lowest in children because of negative peer pressure; parental
      example, including an attitude of safety consciousness and parental concern;
      higher levels of education; access to discounted helmets; public campaigns to
      promote helmet use; and, most importantly, appropriate legislation. But it is
      clear that appropriate legislation making helmet use compulsory for all cyclists
      is the only effective method for increasing helmet use, especially by young
      cyclist. Such legislation would reduce a mortality rate among young cyclists that
      has been equated to the mortality caused by some childhood infections in the pre
      vaccination era. Some argue that physicians have a particular responsibility for
      promoting effective legislation for mandatory helmet use so that young children
      can be 'vaccinated' against the risk of the modern childhood epidemic; fatal head
      injury while cycling.

PMID- 8571012
TI  - [Circadian profile of blood pressure and heart rate in geriatric patients with
      and without dementia].
AB  - In this report, investigations on circadian blood pressure fluctuations in
      geriatric patients with or without senile dementia are reported. 24 patients of a
      nursing home in Zurich have been included in the study. In senile patients
      without dementia, persistence of circadian blood pressure rhythm, including a
      nocturnal decrease of blood pressure, could be demonstrated. In very old
      patients, however, reduced day-night amplitudes or loss of day-night rhythm,
      respectively, were observed. In the group of demented patients and in a subgroup
      including only patients with Alzheimer's disease, loss of circadian blood
      pressure rhythm and a lacking drop of nocturnal blood pressure values were found,
      while diurnal rhythmicity of the heart rate remained unchanged. Furthermore, our
      results demonstrate that there was no circadian blood pressure rhythm detectable
      in the five patients with Parkinson's syndrome (with or without dementia). The
      results of this study suggest that degenerative processes of the central nervous
      system interfere with circadian blood pressure rhythm.

PMID- 8571013
TI  - [A case from practice (338). Bartter's syndrome].

PMID- 8571014
TI  - [Current therapy of esophageal varices hemorrhage].
AB  - Acute bleeding from esophageal varices is a medical emergency. It requires a
      structured therapeutic strategy which is adapted to the local resources. The
      primary goal is to stop bleeding, preferably by endoscopic sclerotherapy or
      ligation. In situations where endoscopic intervention is not possible as a first
      line treatment, therapy with balloon tamponade or vasoactive drugs (terlipressin
      or octreotide) are options to be followed as soon as possible by sclerotherapy or
      ligation. After successful hemostasis, the next goal is to prevent rebleeding.
      This is achieved primarily by eradicating sclerotherapy or ligation. In special
      situations, long-term therapy with a non-cardio-selective beta receptor blocker
      is an alternative. The combined approach of sclerotherapy or ligation plus beta
      receptor blocker has no significant advantage. Primary prophylaxis of bleeding
      from esophageal varices by long-term beta receptor blocker therapy is advised in
      patients with medium-sized or large varices. Apart from strategies aimed at the
      therapy or prophylaxis of bleeding from esophageal varices, measures to prevent
      and treat chronic liver diseases should be implemented in order to reduce the
      development of liver cirrhosis as the leading cause of esophageal varices.

PMID- 8571015
TI  - [Esophageal varices bleeding: causes and pathophysiology].

PMID- 8571016
TI  - [Bleeding esophageal varices: endoscopic therapy (sclerosing, rubber band
      ligation and balloon tamponade].

PMID- 8571017
TI  - [Drug therapy of acute esophageal varices bleeding (vasopressin, terlipressin,
      somatostatin)].

PMID- 8571018
TI  - [Esophageal varices. Shunt therapy and embolization].

PMID- 8571019
TI  - [Esophageal varices. Surgical shunts].

PMID- 8571020
TI  - [Esophageal varices. Drug treatment of recurrent bleeding and its prevention:
      beta blockers].

PMID- 8571021
TI  - [Wrong diagnosis: psychosomatic illness].

PMID- 8571022
TI  - [Postpolio syndrome: retrospective study in a former polio clinic].
AB  - Delayed consequences of polio virus infection are of growing interest because of
      the increasing incidence of new symptoms in patients who previously had
      poliomyelitis. We examined 121 patients with an earlier diagnosis of acute
      anterior poliomyelitis for features of the postpolio syndrome using the criteria
      of Halstead and found evidence of the syndrome in 68.07% of the patients.
      Meaningful management of these patients requires recognition of the clinical
      features of the condition and a collaborative approach involving physicians,
      physiotherapists, psychotherapists and social workers.

PMID- 8571023
TI  - [Breast-preserving treatment of breast carcinoma: analysis of surgical,
      pathologic-anatomic and radiotherapeutic data of 291 cases].
AB  - 291 breast cancer patients treated with conserving surgery and subsequent
      locoregional irradiation were studied. The method of surgery consisted of 200
      lumpectomies, 76 quadrantectomies and 15 with either a wide excision or with an
      atypical resection. In at least 42.6% (124 out of 291), the tumor had been within
      10 mm distance to the margin of resected specimen, in 13.4% (39 out of 291) the
      tumor even reached the border. In the other reports, a numerical description of
      the distance to the margins was not given. Postoperative radiotherapy was applied
      with 50 Gy cobalt-60/6-MeV photons to include the whole breast. A boost of
      tangentially opposed photon beams was added, replacing a technique with direct
      electron fields used in an earlier period during three years. The supraclavicular
      fossa received 46 Gy, the retrosternal pathway was covered with 45 to 50 Gy
      photons/electrons. Locoregional failure after an average observation time of 39.5
      months was 4.5% (13 out of 291), within the target volume 3.8% (11 out of 291.
      The 39 cases on which the tumor reached the margin of resection, 92.3% (36 out of
      39) remained free of recurrences. With a tumor-free resection line but a maximal
      distance of 10 mm, one recurrence (1.2% or 1 out of 85) was found. With the
      application of tangential photon beams to the tumor bed, which technically
      allowed sparing skin parts but also slightly reduced daily doses, the incidence
      of telangiectasis could be lowered to 2.5%. An anatomical was model was
      constructed to resemble a patient in the treatment position. Dosimeters were
      implanted and verified by computed tomography. Measurements of the radiation
      fields were performed within the breast, the lung and along the mammaria-interna
      chain. Minimal angle changes of 5 degrees decreased the retrosternal dose down
      with the amount of 56.5%, 10 degrees of 75% and 15 degrees of 85.7%. In contrast,
      moving the central axis medially by 1 cm and 2 cm increased the lung dose 2.2 and
      4.4 times, respectively, whereas the dose within the breast remained almost
      equal. This emphasizes the importance of identical positioning, which must be
      realized 25 to 35 times throughout the course of therapy, often with different
      staff! Precision and consistent positioning are the main priorities. If these
      goals are achieved, lumpectomy with subsequent high-dose radiotherapy respecting
      cosmetics provides patients with excellent quality of life.

PMID- 8571025
TI  - [A case from practice (339). Exhaustion, collapse of obscure etiology--most
      likely of psychosomatic origin and/or alcohol-induced].

PMID- 8571024
TI  - [Hormonal contraception has no effect on the atherogenicity of blood lipids:
      results of a prospective open-label multicenter study in 1321 patients].
AB  - In a prospective open-label multicenter trial, safety, tolerance, cycle control
      and changes in lipid metabolism before and during intake of a low-dose hormonal
      contraceptive (gestodene 75 mcg + ethinylestradiol 30 mcg) have been investigated
      under normal conditions of a general or gynecology practice (232 testing
      physicians, 1321 women). The atherogenic index remained almost unchanged over six
      cycles observed (3.3 before drug intake vs. 3.28 after drug intake, cycle 6). HDL
      cholesterol levels increased significantly in the period between prestudy and
      cycle 6 (+4.4%, p < 0.0001). A very good cycle control was demonstrated, and
      reliable contraception was achieved, combined with excellent general tolerance.
      The preparation conclusively suits very well for oral hormonal contraception.

PMID- 8571027
TI  - [Internet (1)].

PMID- 8571026
TI  - [Modified concept of psychopathy].
AB  - After a brief recapitulation of the conceptual history of the term 'psychopath',
      the author presents the modern view of 'psychopathy' coined by US-American
      researchers. This new concept found its most concise, operationalized form in the
      20 diagnostic criteria of Robert D. Hare's 'psychopathy Checklist-Revised' (PCL
      R). In sharp contrast to older German concepts, which were not confined to
      antisocial characters, the American 'psychopathy' diagnosis covers a core group
      of delinquents showing marked unscrupulousness and elevated proneness to relapse.
      After having listed a number of empirical findings confirming the validity of the
      diagnosis 'psychopath' on different levels of investigation, the author
      demonstrates the close connection between personality traits and behavioral
      characteristics of this highly problematic group, making use of the so-called
      functional circle designed by J. v. Uexkull.

PMID- 8571028
TI  - [Continuing education at the Val d'Hebron General Hospital].

PMID- 8571029
TI  - [The nurse and children (1). Identity, critique and morality of toys and books
      for children].

PMID- 8571030
TI  - [Multivariate analysis. Routine analysis of fitness. Its application to the
      interpretation of general public health indicators].

PMID- 8571031
TI  - [Models in community nursing].

PMID- 8571032
TI  - [The sacrum. Dorsal aspect].

PMID- 8571033
TI  - [Cystourethroscope. (Rigid cystoscopy)].

PMID- 8571034
TI  - [Cardiac tamponade ... a tight situation].

PMID- 8571036
TI  - [Function of pneumocytes II].

PMID- 8571035
TI  - [Sudden infant death. A lesson of modesty for physicians and researchers].

PMID- 8571037
TI  - [Vibration therapy, past and present].

PMID- 8571038
TI  - [Coronary recanalization in the acute phase of myocardial infarction].
AB  - Early reopening of the infarct-related artery limits infarct size, preserves left
      ventricular function and reduces short and long term mortality rate. The earlier
      the reopening, the higher the benefit, the best results being obtained within the
      first 3 hours, but remaining significant up to 12 hours after onset of symptoms.
      In addition, complete reperfusion of the infarct-related artery without delay of
      distal filling enhances the results. Early reopening can be obtained with use of
      intravenous thrombolysis. The indication of rescue angioplasty in case of failed
      thrombolysis or of immediate, deferred or elective adjunctive angioplasty after
      successful thrombolysis remain debated. Contraindications to thrombolysis exist
      in about 13% of patients, in whom the only solution is direct angioplasty without
      thrombolysis.

PMID- 8571039
TI  - [Treatments of acute myocardial infarction other than recanalization ].
AB  - During the past 15 years, the in-hospital mortality of patients with acute
      myocardial infarction has considerably declined. The 2 main reasons for this
      decrease in mortality have been the introduction of intensive coronary care
      units, and reperfusion of myocardial infarction, either by coronary thrombolysis
      or percutaneous transluminal coronary angioplasty. However benefits of other
      therapies should not be overlooked. General care measures should include: close
      supervision, bed rest, liquid diet, analgesics, reduction of anxiety, oxygen
      therapy, intravenous heparin and aspirin, monitoring of blood pressure and heart
      rate. beta-blockers and angiotensin-converting enzyme inhibitors, combined or not
      with thrombolytic therapy, are also available to reduce the rate of mortality and
      morbidity. The benefits to be expected from these 2 medications combined have not
      yet been demonstrated, so that it appears reasonable in common practice to choose
      either drug according to the patient's functional state.

PMID- 8571040
TI  - [Treatment of unstable angina].
AB  - Adequate treatment of unstable angina, initiated soon enough in the setting of a
      coronary care unit, avoids evolution towards myocardial infarction in more than
      90% of the patients. Treatment consists of a combination of anti-thrombotic and
      anti-ischemic therapies. Oral beta-adrenergic blockers and intravenous nitrates
      represent the usual anti-ischemic treatment; calcium antagonists will be
      prescribed as an adjunct therapy if the response is insufficient or if a
      vasospastic mechanism is suspected. Anti-thrombotic treatment usually consists of
      a combination of low dose aspirin and intravenous heparin. Twelve hours are
      usually sufficient to titrate this medical regimen and to assess its efficacy; if
      myocardial ischaemia persists or recurs despite this therapy, urgent coronary
      angiography and subsequent revascularization are warranted. Usually ischaemia is
      adequately controlled by medical therapy, elective coronary angiography is
      nevertheless useful to screen high risk patients (left main and severe three
      vessel disease) needing coronary artery bypass graft. In most cases however
      revascularization, by surgery or angioplasty, will be considered only if
      ischaemia at rest or induced by exercise, recurs despite optimal medical
      treatment.

PMID- 8571041
TI  - [Medical treatment of patients with stable angina pectoris].
AB  - Stable angina is usually due to coronary atherosclerosis and complicated by
      myocardial lesions responsible for ischaemic myocardiopathy. Tobacco suppression,
      aspirin and cholesterol lowering drugs especially statins are the best way to
      slow coronary atherosclerosis progression. beta-blockers, physical conditioning
      are the two main medical means to suppress anginal symptoms. Converting enzyme
      inhibitors and beta-blockers are useful to slow the progression rate of ischaemic
      cardiomyopathy. Revascularisation procedures are combined with medical treatment
      and help treating symptoms and preventing myocardial lesions.

PMID- 8571042
TI  - [Indications for percutaneous angioplasty and coronary surgery in stable angina
      pectoris].
AB  - Coronary by-pass surgery and percutaneous transluminal angioplasty (PTCA) have
      changed the prognosis and life quality of patients with stable angina. Medical
      treatment and myocardial revascularisation are both useful and most often
      complementary. Coronary by-pass surgery is indicated in the treatment of coronary
      left main disease and three-vessel disease with poor left ventricular function.
      PTCA is the best choice in patient with one-vessel disease resulting in
      myocardial ischaemia. Discussion remains open in other cases mainly in stenosis
      of proximal left anterior descending artery. Often the ultimate choice results
      from the limits of each technique: sapheneous by-pass occlusion or coronary
      artery restenosis after PTCA. New techniques and devices in revascularization are
      expected to improve prognosis:use of arterial by-pass grafts, gene transfer,
      local drug delivery.

PMID- 8571043
TI  - [Silent myocardial ischemia].
AB  - Silent or painless myocardial ischaemia is common: it can occur in totally
      asymptomatic patients, in stable or unstable angina sufferers, or after
      infarction. In most instances, it is detected electrocardiographically (or
      ambulatory recording by treadmill test). It is essential to establish a firm
      diagnosis because patients are high-risk subjects. Tomoscintigraphy or
      echocardiography, on exertion or after drug stimulation, are therefore to be used
      before it is decided to perform coronary angiography. In all cases treatment is
      required to suppress ischaemia. It should primarily be medical, the choice being
      governed by the results of exploration, and should bear upon anatomical lesions
      and their functional effects. Revascularization, generally by angioplasty, is
      thus increasingly indicated despite the fact that, in contrast to painful
      ischaemia, there are no comparative studies available on painless ischaemia to
      help guiding the treatment decision.

PMID- 8571044
TI  - [Secondary prevention of atherosclerosis: effects on coronary plaques and on
      myocardial ischemia].
AB  - The coronary atherosclerotic plaque progresses in successive stages, determined
      by phenomena such as spasm, thrombosis and inflammation. Studies of regression
      are hindered by methodological problems involving the variability of angiographic
      results over intervals of several years. Longitudinal clinical studies are
      probably more useful. For long-term clinical outcome, it appears that
      stabilisation of young plaques is more important than regression of older
      plaques. To this end, cessation of smoking seems the most effective means;
      progressive plaques are most often seen early in the disease, in patients under
      60 years of age, of whom more than 70% are smokers. The inevitable lack of
      studies as rigorous as those dealing with hyperlipidaemia reduction should not be
      used as a pretext for scruples leading to ignoring the results of clinical
      practice. Prevention by diet is no doubt essential, but prospective studies are
      still rare and biases are numerous. The same is true for physical exercise.

PMID- 8571045
TI  - [Treatment of ischemic myocardiopathy].
AB  - Ischaemic myocardiopathy mandates the control of coronary risk factors and the
      administration of antiplatelet therapy. If myocardial ischaemia exists, an
      antianginal treatment will be prescribed. In case of heart failure, the
      association of an angiotensin-converting enzyme inhibitor and diuretics is
      required. A beta-blocker, especially at low dose, should be discussed according
      to the symptoms. When ischaemic cardiomyopathy is asymptomatic, an angiotensin
      converting enzyme inhibitors is also likely to benefit the patient. Coronary
      revascularization may be indicated according to the importance of both residual
      ischaemia and resistance to medical therapy.

PMID- 8571046
TI  - [Hypoglycemia in children. Diagnostic orientation and emergency treatment with
      posology].

PMID- 8571047
TI  - [Abdominal injury, contusion. Diagnostic orientation and emergency treatment].

PMID- 8571048
TI  - [Infectious diseases during pregnancy (II). Diagnosis, prevention, fetal risks,
      therapeutic consequences].

PMID- 8571049
TI  - [Vomiting. Diagnostic orientation].

PMID- 8571050
TI  - [Contraceptive practices in France].
AB  - Between 20 and 44 years of age, in France, two women out of three use
      contraception; 41% use oral contraception, and 16% the IUD; 5% use condoms, and
      sterilization remains uncommon. Since 1988, when some information was made about
      the AIDS epidemics, condoms have become widely used, as a temporary method,
      especially by young people and people not living as a couple; 59% of women and
      83% of men aged 20-24 ever used condom, and half of the women who had their first
      sexual intercourse during the two last years used condoms.

PMID- 8571051
TI  - [Pharmacology of oral contraceptives].
AB  - Oral contraceptives include two types of steroids; ethinyl-estradiol as the main
      estrogenic component which dose vary from 20 to 50 micrograms per tablet (mostly
      30 to 35 micrograms) and progestins essentially derivatives of 19
      nortestosterone. Derivatives of 19 norprogesterone such as nomegestrol acetate or
      ST 1435 are not used as oral contraceptives but are being evaluated through
      parenteral administration, e.g. implants or transdermal systems. The assessment
      of the pharmacological properties of these progestins indicate a high
      antigonadotropic and a high antiestrogenic properties for levonorgestrel and for
      the newer gestagens as well. Therefore very low doses are being used in the
      current oral contraceptives. However, there is a lower margin of security with
      the low dose contraceptives than with previous standard combinations and
      especially when concomitant medications are ingested such as enzyme-inducing
      agents. Selection of contraceptive methods should be discussed when specific co
      medications are necessary.

PMID- 8571052
TI  - [Vaginal and intrauterine contraception].
AB  - Vaginal contraception (condom, diaphragm and spermicide in pessary, tablet,
      jelly, cream, or sponge form) have been little used in France and generally in
      Europe since the advent of modern contraception with "the pill" and the
      intrauterine contraceptive device. The former methods, when properly used, are
      nevertheless both effective and useful, at least as interim measures. In
      addition, the protection they afford against sexually transmitted diseases and,
      for the condom, against HIV, is not negligible. Finally, the "barrier" methods of
      contraception such as the diaphragm and the condom afford significant protection
      against cancer of the cervix. The intrauterine contraceptive device (IUCD), used
      in France by 14% of women between 15 and 49 years of age and by 90 million women
      throughout the world for whom it is the main reversible means of contraception,
      have a mechanism of action that is still not fully understood. Most IUCD now used
      are made of copper. There are also diffusion IUCD based on progesterone or a
      synthetic progestational hormone which are useful in case of anaemia, menorrhagia
      or dysmenorrhea.

PMID- 8571053
TI  - [Choice and follow-up of contraception without risk factor].
AB  - Every young healthy and truly informed woman may use any contraceptive method.
      Teenagers have to avoid not only pregnancy but also AIDS and other sexually
      transmitted diseases. Therefore they may use condoms when aware of postcoital
      contraception or must use both condoms and oral contraceptives. Non smoker women
      over 40 may choose between combined oral contraceptives, high doses progestogens
      or IUDs. Whatever the age, newer preparations with desogestrel, norgestimate or
      gestodene will be preferentially used due to the absence of clinical and
      metabolic side-effects. Smokers before 35, nonsmoker women over 35 will be
      preferentially given pills with only 20 micrograms ethinyloestradiol.

PMID- 8571054
TI  - [Metabolic and vascular risks with oral contraceptives].
AB  - Despite selectivity in prescriptions and changes in formulations, combined oral
      contraceptives still increase the relative risk of thrombo-embolic accidents. The
      main mechanism implies ethinyloestradiol accumulation in the liver and related
      consequences, not for circulating lipoproteins, but for coagulation/fibrinolysis
      balance. Most serious concerns should be directed to subjects having preexisting
      arterial or venous wall alterations or hemostatic disorders. Restriction of oral
      contraceptive use extended to all subjects suspected of carrying these risks has
      been highly effective for prevention of coronary accidents but less for
      prevention of stroke or venous thrombosis. The crude number of vascular accidents
      remains very low in women below 35 years old, non smokers, without hypertension,
      diabetes, dyslipidemia nor cardiac valve disease, without personal or familial
      history of thrombosis, and without any significant increase in weight, blood
      pressure and triglycerides while using pills.

PMID- 8571055
TI  - [Contraceptions in women with contra-indication to estrogen-progestins].
AB  - Estrogen-progestin pill contra-indications can be related to a metabolic or
      vascular risk or to an estrogen-dependent disease. In the first case, a pregnane
      progestin (chlormadinone acetate or cyproterone acetate) can be used as a first
      choice, because of its good tolerance and absence of deleterious effects on these
      diseases. IUD use is limited due to the risk of infection and a decreased
      efficiency with corticosteroids. Diaphragm plus spermicides or condoms can be
      used in any case and are the only possibilities during the course or just after a
      deep vein thrombosis. In case of estrogen-dependent diseases, high-dose progestin
      is the treatment of the diseases in most of the cases and normethyl-testosterone
      derivatives or other progestin can be used.

PMID- 8571056
TI  - [Contraception and uterine pathology].
AB  - Due to the follow-up it requires, contraception leads to early detection of
      benign and malign uterine lesions. Contraception must not only be effective, but
      at the same time: treat the detected lesion (endometriosis); aid conservative
      surgery (LH-RH analogues, then antigonadotrophin progestin treatment); not be
      deleterious (myomas, endometriosis), be adapted to the detected lesion (condyloma
      and contraindication of IUD).

PMID- 8571057
TI  - [Oral contraception and risk of cancer. Epidemiological aspects of breast and
      gynecological cancers].
AB  - Oral contraceptives are now widely used by healthy women. Their safety for long
      term use is an important issue that has been addressed by numerous
      epidemiological studies. The single main question about the safety of oral
      contraceptives use is its potential effect on the development of breast cancer.
      Several meta-analysis have reviewed all published studies. They provide a
      reassuring picture: oral contraceptive use does not appear associated with breast
      cancer. However, increased risks have been identified in specific population for
      long-term users by young women or before the first full term pregnancy. The use
      of combined oral contraceptives is associated with lower risks both of
      endometrial cancer and ovarian cancer. Because of methodologic problems, the
      results on the risk of cervical cancer and its precursors remain unclear.

PMID- 8571058
TI  - [RU 486. Contragestion, contraception].
AB  - The word contragestion is used to name voluntary interruption of very early
      pregnancy. The RU associated with an analogue of prostaglandine E1 is used in
      this indication until 49 days of amenorrhea. Based on a study carried out by
      Roussel in 1993 on 488 patients, the rate of efficacy is 96.9%. Failures are:
      ongoing pregnancy 1.8%, hemostatic surgical procedure 0.4%, stopped but non
      expelled pregnancy 1.8%. Side effects are mainly pelvic pains but pain killers
      were necessary only for 20% of patients. The contraception with RU 486 has just
      started. The RU seems to be a very efficient post-coital contraceptive when taken
      within 72 hours after an unprotected intercourse. Two trials have had a rate of
      success of 100%. The RU in ordinary contraception could be used either just after
      ovulation or during all the cycle with very low doses. Trials have just started.

PMID- 8571059
TI  - [Perspectives of contraception].
AB  - According to demographic provision, the world population will soon reach 6
      billions. It is therefore urgent to increase women's access to well tolerated,
      efficient, low cost contraceptives. The primary goal is to inform women on their
      reproductive health and on the use of contraceptives. Secondly, new molecules
      should be shortly available: low dose estroprogestins containing new non
      androgenic progestins and 17 beta-estradiol, RU 486 as a post-coital pill,
      levonorgestrel or desogestrel containing IUDs. The daily intake of low dose
      antiprogestins to interfere with endometrial maturation is also currently
      studied. In the future, anti-FSH molecules or tissue-specific steroids could be
      designed.

PMID- 8571060
TI  - [Convulsive seizure. Diagnostic orientation and emergency treatment with
      posology].

PMID- 8571061
TI  - [Conjugated bilirubin jaundice in adults. Diagnostic orientation].

PMID- 8571062
TI  - [Vomiting in infants. Diagnostic orientation].

PMID- 8571063
TI  - [Endometrial cancer. Epidemiology, diagnosis, clinical course, management].

PMID- 8571064
TI  - [Facial paralysis. Diagnostic orientation].

PMID- 8571065
TI  - [Cancer of the rectum. Epidemiology, pathological anatomy, diagnosis, clinical
      course, management and prevention].

PMID- 8571066
TI  - Complete remission of metastatic breast cancer by non-specific immunostimulation
      with a Nocardia opaca cell-wall extract after failure of conventional therapy.
AB  - In a male patient with recurring lung metastases of infiltrating breast carcinoma
      (T2NOMO), primary treatment mastectomy, axillar dissection and local irradiation)
      the tumor metastases developed progressively despite of repeated surgical
      removement, polychemotherapy, and antiestrogen treatment. Active unspecific
      immunotherapy with a Nocardia opaca cell-wall extract, started in the final stage
      of the disease with deterioration of the performance status, resulted within
      several months in a complete remission without serious side effects. The reported
      result suggest that is is worth while to try such bacterial immunomodulators in
      therapy of advanced cancer in spite of many disappointing clinical trials.

PMID- 8571067
TI  - [Plasma volume in polycystic kidney disease].
AB  - Hypertension is a common and serious complication of autosomal dominant
      polycystic kidney disease (ADPKD), occurring early in the course of the disease.
      Disorders of tubular transport of sodium and increased plasma and blood volume
      (PV and BV), as a consequence, are thought to be involved in the pathogenesis of
      hypertension in ADPKD. In order to evaluate PV and BV in early stage of ADPKD, PV
      and BV were measured with radioactive serum albumin dilution technique. Three
      groups of subjects with normal glomerular filtration rate were studied: ADPKD
      hypertensive (ADPKD H, n = 10, age: 36.2 +/- 8.7 y), ADPKD normotensive (ADPKD N,
      n = 15, age: 33.4 +/- 7.4 y), and healthy volunteers (C, m = 8, age: 32.6 +/- 6.8
      y). PV and BV expressed per kilogram of body weight did not differ among the 3
      groups. When PV and BV were expressed per meter square of body surface area,
      diminished BV in the group ADPKD H in comparison to ADPKD N and group c (p <
      0.05) was found, other parameters did not differ between the 3 groups. In
      conclusion--our results do not support the hypothesis of a significantly
      increased PV and BV of patients with ADPKD prior to the onset of hypertension.

PMID- 8571068
TI  - [Lithium clearance in polycystic kidney disease].
AB  - Disorders of tubular transport of sodium are thought to be involved in
      pathogenesis of cyst formation and development of hypertension in autosomal
      dominant polycystic kidney disease (ADPKD). Recently lithium has been proposed as
      a quantitative marker of proximal tubular reabsorption of sodium and lithium
      clearance as a method to analyze tubular sodium handling. To evaluate tubular
      sodium handling in early stage of ADPKD, lithium clearance (600 mg of Lithium
      carbonicum p.o.) was performed in a control group of pts. with ADPKD and normal
      glomerular filtration rate (n = 28), age 19.9 +/- 8.8 years) and in a control
      group of healthy volunteers (n = 43), age 30.3 +/- 9.0 years). Both groups did
      not differ in plasma or urine concentrations of electrolytes; plasma creatinine
      levels were slightly higher in ADPKD group than in controls (83.4 +/0 18.0
      mumol/l vs. 93.4 +/- 24.2 mumol/l, p < 0.05). We did not demonstrate any
      statistically significant difference between the group of ADPKD and control group
      in lithium clearance and in fraction excretion of lithium (23.6 +/- 14.5 vs. 19.5
      +/- 8.7 ml/min, resp. 15.3 +/- 8.8 vs 13.8 +/- 7.8%). Nor proximal tubular
      resorption of sodium, neither distal tubular resorption of sodium did differ
      between the group of ADPKD and control group (86.18 +/- 2.2 vs 84.7 +/- 1.80%
      resp. 94.7 +/- 2.6 vs. 94.5 +/- 3.6%). When comparing parameters of sodium
      handling between pts. with ADPKD and hypertension (6/28) and pts. with ADPKD
      without hypertension no difference was found. In conclusion, we could not
      demonstrate any statistically significant difference in tubular handling of
      sodium, when based on lithium clearance between the groups of ADPKD with normal
      glomerular filtration rate and control group.

PMID- 8571069
TI  - [Preclinical models of the effect of acute renal ischemia on creatinine plasma
      levels].
AB  - The effect of temporary and complete renal artery clamping on the plasma
      concentrations of creatinine (Pcr) and morphologic alterations was studied in the
      remaining kidney of unilaterally nephrectomized rats. It was demonstrated that 20
      minute ischaemia did not entail a significant increase in Pcr although histologic
      changes were already detectable in the kidney. Thirty-minute ischaemia was
      associated with appreciable histologic changes in the kidney even though the rise
      in Pcr was mild and transient. Forty-five and sixty-minute ischaemia was found to
      be associated with severe histologic changes and a distinct increase in Pcr. Seen
      from the perspective of transplantation requiring evaluation of the functional
      status of cadaverous donors, the experimental findings show that normal levels of
      Pcr do not exclude the possible presence of morphologic changes, and that even
      major histologic change may manifest themselves in an insignificant increase in
      Pcr.

PMID- 8571070
TI  - [Comparison of functional and morphologic changes after administration of
      Consupren and Sandimmune in rats with a 5/6 nephrectomy].
AB  - Rats with 5/6 nephrectomy were used to compare the nephrotoxic effects of
      Consupren (cyclosporine A by Galena, Czech Republic) and Sandimmun (Sandoz,
      Switzerland). Twenty-one days after the administration of the same dosage, 10
      mg/kg 24 hr, the blood levels of cyclosporine A were statistically significantly
      higher (P < 0.025) in rats given Consupren than in rats receiving Sandimmun. The
      serum concentrations of creatinine, urea, electrolytes, and osmolality did not
      differ after Consupren and Sandimmun. No significant difference between the two
      drugs was found in urinary excretion or proteinuria. The increase in the weight
      of residual renal parenchyma at 21 days after 5/6 nephrectomy did not differ
      significantly between rats administered Consupren or Sandimmun. Histology
      revealed gross hypergranularities in the juxtaglomerular apparatus equally
      present in both studied groups. Results show no significant differences in any of
      the evaluated parameters of the functional capacity of residual renal parenchyma
      or in the nephrotoxic effect as demonstrated in the histologic picture.

PMID- 8571071
TI  - [Concurrent engineering].
AB  - Concurrent engineering is a new attempt to the theoretical and practical
      synthesis of human activities, especially of those ones focusing to industrial
      production or deep to influencing human society. Although its title sound near to
      technology terms, concurrent engineering does not miss medicine, ecology, social
      security and other disciplines. From the methodological viewpoint, concurrent
      engineering represents a synthesis of a wide spectrum of branches of sciences and
      technology; that synthesis is primarily stimulated by commercial aspects,
      supported by the interest coming from production, control of the society and
      business. But that synthesis leads to a rich process of discovering
      interdisciplinary relations at the theoretical level, supported by the powerful
      tools of modern information processing, knowledge representation and exact remote
      transfer of symbolic, graphic and acoustic information.

PMID- 8571072
TI  - [Jaroslav Hlava--60 years since his death].

PMID- 8571073
TI  - [An important anniversary of Dr. Frantisek Samberger (1871-1944)].

PMID- 8571074
TI  - [Experimental models of polycystic kidney disease].
AB  - An overview of actually accepted hypothesis of etiology and pathogenesis as well
      as overview of experimentally induced models of autosomal dominant polycystic
      kidney disease (ADPKD) is presented. Though chemically induced renal cysts in
      rats and other small laboratory animals fed by antioxidants (diphenylamine and
      s.o.) represent the commonest experimental model, strains of animals with
      inherited cystic kidney disease were inbred too. Experimental works on tissue
      cultures derived from patients with ADPKD, which are aimed especially on study of
      epithelial changes (epithelial hyperplasia and s.o.), deserved special attention.
      On conclusion, advantages of the different models and next steps necessary to
      accomplish for understanding etiology and pathogenesis of ADPKD are indicated.

PMID- 8571075
TI  - Reliability of blood alcohol determinations at clinical chemistry laboratories in
      Sweden.
AB  - Known concentrations of ethanol, methanol, isopropanol and its metabolite acetone
      were added to plasma or whole blood and aliquots of each specimen were sent to
      clinical chemistry laboratories in Sweden as a declared collaborative study. All
      participants used gas-liquid chromatography (GC) for quantitative determination
      of ethanol and other low molecular weight volatiles. The mean within laboratory
      precision for analysis of ethanol, expressed as coefficient of variation (CV),
      was 4.7% (range 0-15%). The corresponding between-laboratory CV spanned from 8.0
      to 19.4% for 23 control specimens analysed between 1987 and 1992. The mean
      concentration of ethanol reported was not significantly different from the target
      value assigned. Between 0 and 3 laboratories reported deviant results (Z-score >
      1.96) for each of the control specimens. One laboratory reported the presence of
      methanol instead of ethanol and three laboratories saw traces of acetone instead
      of the actual concentration present. One laboratory failed to report that
      methanol was present and another failed to report the presence of isopropanol.
      The between-laboratory CV ranged between 9.4 and 30.3% for analysis of methanol
      in 8 control specimens. The larger variability between laboratories compared with
      within laboratories probably reflects the different calibration procedures used,
      such as the preparation and source of the alcohol standards.

PMID- 8571076
TI  - Effect of long-chain mono-unsaturated and n-3 polyunsaturated fatty acids on
      postprandial blood and liver lipids in rats.
AB  - The effects on blood and liver lipids after feeding rats with concentrated
      fractions from fish oil consisting of mono-unsaturated fatty acids (80% C20:1 and
      22:1) or n-3 polyunsaturated fatty acids (85% C20:5 and 22:6 n-3) were examined.
      Mono-unsaturated fat had no effects on plasma triacylglycerol, total cholesterol
      phospholipids or unesterified fatty acid as compared to controls (lard). However,
      n-3 polyunsaturated fatty acid-fed animals showed a significant decrease in
      plasma triacylglycerol (74%), phospholipids (40%) and unesterified fatty acids
      (52%). The concentrated fractions had no effects on liver lipids. While the n-3
      diet increased peroxisomal beta-oxidation 2.5-fold, there was only a slight
      increase with the mono-unsaturated diet. The fatty acid composition in plasma and
      liver phospholipids was changed with the various diets; 20:4 n-6 was
      significantly reduced in plasma and liver with the mono-unsaturated diet, and
      with the n-3 diet in liver. The mono-unsaturated diet, and especially the n-3
      diet, increased the 20:5 n-3 level in both plasma and liver. Our results indicate
      that long-chain mono-unsaturated fatty acids in fish oil do not change the levels
      of plasma lipids. The beneficial role of fish oil on the level of blood lipids,
      may therefore be mostly attributed to the effects of long-chain n-3 fatty acids.
      However, the low 20:4 n-6 and high 20:5 n-3 levels in plasma and liver
      phospholipids with the concentrated mono-unsaturated fatty acid diet may be of
      importance for a favourable haemostatic balance with regard to cardiovascular
      diseases.

PMID- 8571077
TI  - No effect of beta-carotene supplementation on the susceptibility of low density
      lipoprotein to in vitro oxidation among hypercholesterolaemic, postmenopausal
      women.
AB  - The effect of beta-carotene on the susceptibility of low density lipoprotein
      (LDL) to oxidative modification was investigated in a double-blind, randomized
      placebo-controlled study. Hypercholesterolaemic, postmenopausal women were given
      30 mg beta-carotene per day (n = 15 subjects) or placebo capsules (n = 15
      subjects) for 10 weeks. They were instructed to follow the American Heart
      Association Step One diet. LDL, isolated before and after treatment was subjected
      to copper-catalysed lipid peroxidation. There were no significant differences
      between LDL from the beta-carotene and placebo groups, as assessed by measuring
      the lag time for formation of conjugated dienes; the rate of formation and the
      amount of conjugated dienes formed; the amount of lipid peroxides generated; and
      the relative electrophoretic mobility, at baseline and after treatment. Dietary
      records showed that the subjects were consuming similar amounts and types of fat.
      No significant differences were found in the lipid composition and fatty acid
      pattern of LDL from the two groups. In conclusion, the results indicated that
      supplementation with beta-carotene in non-smoking, hypercholesterolaemic,
      postmenopausal women had no protective effect on the susceptibility of LDL to
      copper-catalysed modification in vitro.

PMID- 8571078
TI  - A polymerase chain reaction-based method for the semiquantitative study of
      interleukin-8 mRNA in human basophil leukocytes.
AB  - We examined a potential method for quantitative analysis of cytokine expression
      patterns in purified human basophil leukocyte preparations. Basophil mRNA was
      reverse transcribed and cytokine cDNA levels determined by competitive polymerase
      chain reaction (PCR) with internal standard cDNAs constructed by site-directed
      mutagenesis. Co-reverse transcribed glyceraldehyde-3-phosphate-dehydrogenase
      (GAPDH) cDNA levels were used as an internal control to correct for unequal
      efficiencies in RNA isolation and reverse transcription. The method was subjected
      to a statistical validation giving the within series precision of the analysis.
      This method was used to examine interleukin-8 expression patterns in basophils
      from different donors. The results from this study revealed increased interleukin
      8 mRNA levels after in vitro challenge with a variety of stimuli.

PMID- 8571079
TI  - Serum lipoprotein levels in genetically hypercholesterolaemic RICO rats: effects
      of a high-sucrose-cholesterol diet without or with altered magnesium and fluoride
      content.
AB  - Genetically hypercholesterolaemic RICO rats (male, 6 weeks old) were randomly
      distributed into 6 experimental groups. The zero-time basal group A was
      sacrificed at the start of the experiment while the other groups were fed for 6
      weeks and then sacrificed. Group B was fed a stock diet. Control group C was fed
      a high-sucrose (45%) diet with 0.5% added cholesterol. In the diet of group D,
      only the magnesium (Mg) content was reduced from the level of group C (883 ppm)
      to 200 ppm. The diet of group E was the same as that of group D with the addition
      of 12 ppm of fluoride (F) and the diet of group G was the same as that of group
      E, but with its Mg content elevated from 200 ppm to 300 ppm. Analysis of aortic
      blood samples, taken before sacrifice, indicated significant increases in total
      serum cholesterol (p < 0.01), very low density lipoprotein (VLDL) (p < 0.001) and
      low density lipoprotein (LDL), (p < 0.001) cholesterol, and a trend to lower high
      density lipoprotein (HDL) cholesterol in group C, as compared to group B.
      Significantly lower total (p < 0.05), VLDL (p < 0.01) and LDL (p < 0.01)
      triglycerides were observed in group C when compared to group B. The LDL
      phospholipids were significantly higher in group C (p < 0.001) than in group B.
      When cholesterol levels in groups D, E and G were compared with group C, the VLDL
      cholesterol in group E and the LDL cholesterol in group G were slightly but
      significantly (p < 0.05) reduced, while total cholesterol and the other
      subfractions were unaltered. The LDL triglycerides of groups E and G were
      significantly smaller still than the already small fraction in group C. The VLDL
      triglyceride in group E was significantly lower than that of group C (35%
      reduction, p < 0.001), D and G (p < 0.05). Phospholipids were slightly but
      significantly reduced in the VLDL fraction of group E and in the LDL fraction of
      group G (p < 0.05 and 0.01, respectively), as compared to those of group C.

PMID- 8571080
TI  - Influence of intra-osseous infusion of a small volume of hyperosmotic fluid on
      beta-adrenergic function in circulating lymphocytes from bled pigs.
AB  - The regulation of beta-adrenergic function in circulating mononuclear leukocytes
      was evaluated during an episode of haemorrhagic shock treated by intra-osseous
      infusion of a small volume of hyperosmotic fluid. Two groups of piglets (n = 14)
      were anaesthetized with ketamine and bled to a mean arterial pressure of 40 mmHg.
      After 45 min the animals were randomized to receive 100 ml of either hyperosmotic
      (2.4 mol l-1) or iso-osmotic (0.29 mol l-1) fluid (equal volumes of
      glucose/sodium chloride) into the tibial bone marrow. Observations of
      haemodynamic variables and levels of plasma catecholamines and cAMP of
      circulating mononuclear leukocytes were carried out for 70 min. Infusion of
      hyperosmotic fluid enhanced the circulatory performance and attenuated the plasma
      catecholamine release significantly (p < 0.05) compared to the corresponding
      values in the animals that had iso-osmotic fluid infusion. Measurements of
      unstimulated and isoprenaline-stimulated cAMP levels in mononuclear lymphocytes
      indicated that the high plasma catecholamine levels in the iso-osmotic treatment
      group induced a desensitization of the beta-adrenoceptors 70 min after initiation
      of the shock. This effect was not seen in animals that had undergone hyperosmotic
      infusion.

PMID- 8571081
TI  - Phospholipid molecular species with eicosapentaenoic acid (20:5(n-3)) are less
      stable than species with arachidonic acid (20:4(n-6)) in isolated rat liver
      cells.
AB  - We have studied the incorporation of [1-14C]20:5(n-3) and [1-14C]20:4(n-6) in the
      molecular species of phosphatidylcholine (PC) and phosphatidylethanolamine (PE)
      in isolated rat liver cells. These two fatty acids are present in very different
      amounts in endogenous phospholipids, with 20:4 as one of the major fatty acids
      and 20:5 as a minor and very diet-dependent constituent. The main phospholipid
      species formed from 20:4(n-6) were 16:0-20:4 and 18:0-20:4. When formed, they
      were stable during incubations of liver cells for 2-3 h. The main species formed
      from 20:5(n-3) were 16:0-20:5 and 18:0-20:5. After formation, 16:0-20:5 and to a
      lesser degree 18:0-20:5 were, however, degraded during 1-2 h of incubation,
      especially in PC. Only small amounts of 22:5(n-3) and very little 22:6(n-3) were
      formed from 20:5(n-3) and small amounts of 22:4(n-6) were produced from 20:4(n
      6). With 20:4(n-6) and 20:5(n-3) as substrates, 20:4-20:4 and 20:5-20:5 molecular
      species respectively were initially formed in PC and PE but both species were
      rapidly degraded.

PMID- 8571082
TI  - Separate estimation of biological and analytical variance components when
      quantities and reagents are unstable.
AB  - A model for reliable estimation of variance components for biological within- and
      between-subject variation as well as for analytical variation when both the
      quantity and the reagents are unstable has been established. This model was
      applied to the alpha-interferon receptor on human leucocytes which involves two
      major problems. First, the receptor has to be quantified within a few hours after
      blood sampling, and second, the reagents for the measurement procedure must be
      used within 2 weeks. For the number of receptors per cell the biological
      estimates of coefficients of variation were 14% for within-subject variation and
      20% for between-subject variation, respectively. For the dissociation constant
      both estimates were zero as expected. The model is robust and applicable to other
      systems with unstable quantities and reagents.

PMID- 8571083
TI  - A novel function of haptoglobin: haptoglobin-haemoglobin complex induces
      apoptosis of hepatocarcinomatous Hep 3B cells.
AB  - Haptoglobin-haemoglobin complex (Cx) showed a cytotoxic effect on the growth of
      Hep 3B (human hepatocellular carcinoma) cells, dose dependently. The
      antiproliferative effect of Cx on the multiplication of Hep 3B cells was
      augmented by the presence of prostaglandin (PG) D2. Antihuman Hb IgG abolished
      the effect of Cx, dose-dependently, which indicates that the antiproliferative
      effect of Cx really is exerted by Cx. Hep 3B cells treated with Cx showed the
      characteristic biochemical changes of apoptosis, such as DNA fragmentation which
      was blocked by pretreatment with cycloheximide, and the increase of
      transglutaminase expression. Thus, the antiproliferative effect of Cx against Hep
      3B cells occurs via the typical apoptotic pathway.

PMID- 8571084
TI  - Third generation time-resolved immunofluorometric TSH assay for automatic
      immunoassay system evaluated.
AB  - We evaluated a new, third generation assay for serum thyrotropin (TSH) based on
      time-resolved fluorescence (AutoDelfia hTSH Ultra) for the 1235 AutoDelfia
      automatic immunoassay system. The functional sensitivity of the TSH assay was
      0.007 mIU l-1 (between-assay CV, 20%). The between-assay imprecision was CV 4.1
      7.7%, between TSH concentrations of 0.026 and 23.8 mIU l-1. The within-assay
      imprecision was CV 1.2-1.5% between TSH concentrations of 0.5 and 12 mIU l-1. The
      degree of agreement between the AutoDelfia hTSH Ultra assay and a second
      generation TSH-IRMA was studied. The mean difference was -0.04 (SD 0.28) mIU l-1
      at concentrations between 0.22 and 52 mIU l-1. Serum TSH concentrations of
      euthyroid subjects, hypothyroid and hyperthyroid patients as well as those of
      patients with non-thyroidal illness, and thyroid carcinoma patients with TSH
      suppressive thyroxine treatment were analysed. The AutoDelfia automatic
      immunoassay system offers many benefits in sensitivity, precision, speed, output
      rate, time and convenience. Overnight runs are possible, and the system is easy
      to operate.

PMID- 8571085
TI  - Glucocorticoids inhibit the synthesis rate of type III collagen, but do not
      affect the hepatic clearance of its aminoterminal propeptide (PIIINP).
AB  - The aminoterminal propeptide of type III procollagen (PIIINP) is a marker of type
      III collagen metabolism. The serum concentration of PIIINP is increased during
      inflammation, probably reflecting stimulated biosynthesis of type III collagen.
      Serum PIIINP decreases during glucocorticoid treatment. This has been interpreted
      as an inhibited biosynthesis of type III collagen. However, circulating PIIINP is
      extracted by the liver, and the decrease in serum PIIINP may also be caused by an
      increased hepatic elimination. In the present study we investigated the influence
      of intravenous methylprednisolone on the serum PIIINP level in pigs combined with
      a simultaneous determination of the hepatic extraction of PIIINP. The serum level
      of PIIINP decreased by approximately 30% within 2 h following glucocorticoid
      injection (p < 0.01). The initial hepatic extraction ratio of PIIINP was 0.15
      (range 0.05-0.33) and neither changed after administration of methylprednisolone
      nor differ from that of the controls. Injection of methylprednisolone did not
      influence the gel filtration profile. The results of this study confirm the
      previous finding of serum PIIINP being decreased following glucocorticoid
      administration, but disprove the hypothesis that alterations in the liver
      extraction of PIIINP explain the decrease.

PMID- 8571086
TI  - Biological variation of serum and urinary magnesium in apparently healthy males.
AB  - The biological variations of serum (S-) magnesium and urinary (U-) magnesium
      concentrations and excretions have been investigated. Serum samples, 24-h and
      fasting urinary samples were collected from each of 60 supposedly healthy male
      volunteers. In addition, 12 volunteers collected additional samples 7 and 112
      days after the initial sample. The reference interval for S-magnesium was 0.765
      0.997 mmol l-1. The biological variation for S-magnesium was 3.2% within subjects
      and 7.4% between subjects. This indicated an index of indivduality of 0.5, which
      means that significant changes in S-magnesium can occur within the limits of the
      reference interval, and that serial determinations of S-magnesium might prove
      useful as an indicator of changes in whole body magnesium status. It is, on the
      other hand, unlikely that a single determination of S-magnesium can be used in
      assessing whole-body magnesium status in the individual. The reference interval
      for the 24-h U-magnesium excretion, corrected for surface area, was 1.306-4.762
      mumol min-1 1.73 m-2. The 24-h U-magnesium excretion exhibited a biological
      within-subject variation of 36% and a between-subject variation of 26%. The 24-h
      U-magnesium excretion did not correlate with S-magnesium, and only slightly (r =
      0.58) with the fasting U-magnesium/creatinine concentration. This, and the very
      large coefficients of variation, make it unlikely that the renal magnesium
      excretion can be used as a measure of whole body magnesium status, or that
      changes in the renal magnesium excretion can be used as a measure of changes in
      whole body magnesium status.

PMID- 8571087
TI  - Evaluation of research--a difficult but necessary task.

PMID- 8571088
TI  - Reproductive disorders due to chemical exposure among hairdressers.
AB  - The evidence for reproductive disorders due to chemical exposure among
      hairdressers was evaluated. To this end, a literature study was conducted on
      Medline for the years 1985-1993. Reproductive disorders in humans were described
      for solvents such as ethanol and dichloromethane found mainly in hair sprays.
      Reproductive effects of several dye formulations, ethylene glycol ethers,
      nitrosamines, formaldehyde, hexachlorophene, and phthalic esters cannot be
      excluded, but few human data on low concentrations of these agents were
      available. Associations with menstrual disorders and spontaneous abortions were
      found in epidemiologic studies focused on hairdressers. Other studies showed
      inconsistent results, probably due to methodological shortcomings
      (misclassification of exposure, small sample sizes). It is concluded that there
      is little evidence for reproductive disorders among hairdressers to date. Limited
      availability of human data and unknown effects of chemical mixtures call for
      future research focused on human reproductive risks among hairdressers with
      emphasis on exposure assessment in the hairdressing salon.

PMID- 8571089
TI  - Skin symptoms after the reduction of electric fields from visual display units.
AB  - OBJECTIVES: The objective of this work was to determine whether facial skin
      symptoms are reduced by decreasing static and low-frequency electric fields
      produced by visual display units. METHODS: The electric fields were reduced by
      electric-conducting screen filters. Twenty subjects took part in the study while
      working at their ordinary jobs, first two weeks without any filter, then two
      weeks with an inactive filter and two weeks with an active filter (or in reversed
      order). The inasctive filters were identical to the active ones except that the
      ground cable was cut. Measurements showed that the inactive filters reduced the
      static electric fields nonsignificantly less than the active filters. For
      extremely low-frequency fields the difference was greater, and the active filters
      reduced the very low-frequency fields significantly more than the inactive ones.
      RESULTS: Most symptoms were less pronounced with active filters than with
      inactive filters. The differences were small, and for one symptom only, tingling,
      pricking or itching, the result was statistically significant. The recorded
      physical and psychosocial factors did not explain the reduction with the use of
      active filters. Days with a long period spent near a visual display unit resulted
      in significantly more pronounced symptoms than days with short time. The findings
      registered by a dermatologist did not reveal any consistent difference between
      the two periods with filters. CONCLUSION: The results weakly support the
      hypothesis that skin symptoms can be reduced by a reduction of electric fields.

PMID- 8571090
TI  - Fiber exposure assessment in the Swedish rock wool and slag wool production
      industry in 1938-1990.
AB  - OBJECTIVE: A multiplicative model was developed to assess past exposure to
      respirable fibers among rock wool and slag wool production workers in Sweden in
      1938-1990. METHODS: Information on the job titles, work tasks and employment
      times of 1487 workers exposed to man-made vitreous fibers was obtained from
      company records and interviews with older employees. A mathematical model
      developed earlier for assessing historical fiber exposure, based on factory
      averages, was further developed. Matrices of multipliers for each plant that were
      specific for job title were modified to assess fiber exposure with respect to job
      title and calendar period. The model was based on measurements made in 1977. Two
      methods of exposure assessment were compared, cumulative exposure based on
      factory average (model I) and cumulative exposure based on job title (model II).
      RESULTS: The exposure changed considerably in the two factories during the period
      1938-1990, and it varied also between job titles. The estimated average fiber (f)
      exposure level at the two plants in the middle of the 1940s was 1.32 and 0.78
      f.ml-1. These values are 26 and 16 times higher, respectively, than the exposure
      in 1980. Process changes, as well as the addition of binders and oil, reduced the
      exposure drastically around 1950. The mean cumulative respirable fiber exposure
      for the 1487 subjects was 1.44 (range 0.05-18.40) f.ml-1.year. The cleaners had
      14 times higher annual fiber exposure than the preproduction workers.
      CONCLUSIONS: Model II was judged to be more valid than model I in assessing
      exposure to man-made vitreous fibers.

PMID- 8571091
TI  - Cancer incidence, mortality and exposure-response among Swedish man-made vitreous
      fiber production workers.
AB  - OBJECTIVE: The objective of this study was to provide an extended follow-up of
      workers in three Swedish plants producing man-made vitreous fibers (MMVF).
      METHOD: Mortality and cancer incidence was investigated among 3539 male and
      female workers, employed for at least one year before 1978. Mortality was
      followed from 1952 to 1990 and cancer incidence from 1958 to 1989. National and
      regional mortality and cancer incidence rates were used to calculate the expected
      numbers. RESULTS: Twenty-seven lung cancer deaths were observed compared with 23
      expected (standardized mortality ratio 117, 95% confidence interval 81-176),
      based on regional mortality. With a latency time of 30 years, the lung cancer
      risk was significantly elevated, but not trend was found for the standardized
      mortality ratio with increasing duration of exposure to MMVF. The lung cancer and
      stomach cancer mortality was higher in the rock wool industry than in the fiber
      glass industry. Fiber exposure from 1938 to 1990 was estimated in the two rock
      wool plants by applying a model for historical fiber exposure estimation,
      specific for different job titles in the rock wool production industry. No
      relationship was found between individually cumulated rock wool fiber exposure
      and lung cancer or stomach cancer risk. CONCLUSIONS: The numbers of lung cancers
      and stomach cancer cases were low and did not therefore allow more general
      conclusions regarding the cancer hazard for exposed workers. A large European
      study in progress will probably allow more precise conclusions.

PMID- 8571092
TI  - Cancer incidence and mortality of patients with suspected solvent-related
      disorders.
AB  - OBJECTIVE: The aim of this study was to study the incidence of cancer and deaths
      from cancer and other diseases among patients referred to the 11 clinics of
      occupational medicine in Sweden between 1967 and 1987 for examination because of
      exposure to organic solvents. METHODS: The cohort comprised 5791 persons, 5283
      men and 508 women. Information about cancer incidence and causes of death was
      collected from the Cancer Register of the National Board of Health and Welfare
      and the National Death Register of Statistics Sweden, respectively. The expected
      values were calculated from the national death rates and incidence rates of
      cancer. RESULTS: The overall mortality rate was close to expected, but the
      mortality rate was decreased for diseases of the circulatory system [standardized
      mortality ratio (SMR) 0.7, 95% confidence limit (95% CI) 0.5-0.9] and increased
      for suicide (SMR 2.0, 95% CI 1.2-3.2). The total cancer incidence was slightly
      elevated [standardized incidence ratio (SIR) 1.2, 95% CI 0.99-1.4], and some
      specific cancer sites showed an increased incidence, although the lower
      confidence limits surpassed one. Malignancies of the lymphohematopoietic system
      and cancer of the uterine cervix had an increased risk (SIR 1.9, 95% CI 1.2-3.2,
      and SIR 3.7, 95% CI 2.2-6.2, respectively). Patients with presumerably high
      solvent exposure had an SIR of 1.4 for all malignancies (95% CI 0.9-2.1) and
      those with presumerably low exposure had an SIR of 1.1 (95% CI 0.9-1.4).
      CONCLUSIONS: The study showed an increased risk for malignancies of the
      hematopoietic system and the uterine cervix among patients originally examined
      with regard to solvent-induced disorders. There was also an increased risk of
      suicide and a decreased risk of death from diseases of the circulatory system.
      There was no increased risk for deaths from mental or neurological disorders.

PMID- 8571093
TI  - Decreased birthweight among infants born to women with a high dietary intake of
      fish contaminated with persistent organochlorine compounds.
AB  - OBJECTIVES: The purpose of the study was to assess reproductive outcomes,
      especially birthweight, and the consumption of fatty fish from the Baltic Sea,
      contaminated with persistent organochlorine compounds, among women from the
      Swedish east coast. MATERIAL AND METHODS: Cohorts of fishermen's wives from the
      Swedish east and west coasts were established and linked to the Swedish Medical
      Birth Register for 1973-1991; 1501 children were born in the eastcoast cohort and
      3553 in the westcoast cohort. Comparisons were made with regional populations and
      between the cohorts. Dietary interviews were made with 69 randomly selected women
      from the cohorts and 69 referents. RESULTS: The women interviewed from the east-
      and westcoast cohorts ate locally caught fish more than twice as often as their
      referents. Compared with the regional population, the women in the eastcoast
      cohort gave birth to an increased number of infants with low birthweights (< 3000
      g), whereas the opposite was seen in the westcoast cohort. Infants in the
      eastcoast cohort had significantly lower birthweights than infants from the
      westcoast cohort (median 3530 versus 3610 g, P < 0.001). Even after adjustment
      for potential confounders, eastcoast affiliation showed an increased risk for low
      birthweight (odds ratio 1.44, 95% confidence interval 1.18-1.76). The effect was
      more conspicuous for boys (odds ratio 1.95) and heavy smokers (odds ratio 3.00).
      CONCLUSIONS: The present data support, but do not prove, an association between a
      high consumption of contaminated fish from the Baltic Sea and an increased risk
      for low birthweight.

PMID- 8571094
TI  - Risk assessment methodologies for carcinogenic compounds in indoor air.
AB  - OBJECTIVES: The purpose of this study was to compare different methods for
      calculating maximal allowable concentrations of potentially carcinogenic
      substances in indoor air. Benzene, tetrachloroethylene, trichloroethylene, and
      vinyl chloride were selected as the model substances. METHODS: Estimates were
      used of carcinogenic potency from quantitative risk assessment, lowest observable
      effect levels (LOEL) from animal experiments and epidemiologic studies combined
      with safety factors, and estimation from occupational exposure limits with safety
      factors. The estimates were compared with actual concentrations in buildings in
      Denmark. RESULTS: Concentrations of benzene, tetrachloroethylene,
      trichloroethylene, and vinyl chloride of the order of 10, 20, 200, and 40 ppb,
      respectively, in indoor air were found to correspond to a 10(-4) lifetime risk of
      cancer. CONCLUSIONS: The estimated maximal allowable concentrations of
      carcinogenic compounds obtained from indoor air by quantitative risk assessment
      using a lifetime risk of 10(-4) or using LOEL values and suitable safety factors
      appear to be comparable and reasonable. Calculations based on occupational
      exposure limits and safety factors generally give comparable or somewhat higher
      values. Using a lifetime risk of 10(-6) for quantitative risk assessment does not
      seem reasonable considering the risks associated with the activities of everyday
      life.

PMID- 8571095
TI  - Visual dysfunction among styrene-exposed workers.
AB  - OBJECTIVES: The present study was undertaken to examine the relation between
      visual functions and occupational exposure to styrene. METHODS: A total of 128
      workers (85% of the total population), from three glass-reinforced plastics
      plants in Canada, agreed to participate in the study. Environmental and
      biological measures were made on the day(s) prior to the assessment of near
      visual acuity (National Optical Visual Chart), chromatic discrimination (Lanthony
      D-15 desaturated panel), and near contrast sensitivity (Vistech 6000). The
      analyses were performed on 81 workers with near visual acuity of at least 1 min
      of arc at 0.5 m. RESULTS: The subjects were relatively young [29 (SD 8) years],
      with little seniority [5 (SD 4) years]. Styrene exposure for 8 h ranged from 6 to
      937 (first quartile 21 mg.m-3, third quartile 303 mg.m-3), depending on the job
      site. The end-shift concentrations of urinary mandelic acid ranged from
      nondetectable to 1.90 mmol.mmol creatinine-1. Significant positive relations were
      found between the internal and external styrene exposure measurements and color
      vision loss adjusted for age, alcohol consumption, and seniority in a multiple
      regression analysis. The multiple regression analysis is also showed that the end
      shift concentration of urinary mandelic acid was inversely related to contrast
      sensitivity at 6 and 12 cycles.degree-1. Logistic multiple regression models
      indicated that the end-shift concentration of urinary mandelic acid was related
      to the prevalences of blurred vision, tearing, and eye irritation. CONCLUSIONS:
      These findings suggest that there is a positive relation between styrene exposure
      and early color and contrast vision dysfunction.

PMID- 8571096
TI  - [Diagnostic markers in calcium nephrolithiasis--current and traditional ideas
      with a new look].
AB  - About 80% of all renal stones contain calcium oxalate and/or calcium phosphate as
      their main crystalline components. The most important risk factors for increases
      in calcium oxalate crystallization are low urine volume, hyperoxaluria and
      hypocitraturia. Hypercalciuria, however, is of secondary importance as a cause of
      increased crystallization: whereas calcium and oxalate crystallize in a 1:1
      ratio, the molar concentration ratio in urine amounts to about 10:1 in favor of
      calcium. Therefore, increases in urinary calcium will not be followed by a rise
      in crystallization as long as oxalate remains constant, whereas even the
      slightest increases in urinary oxalate immediately cause more crystals to
      precipitate. Thus, low calcium diet is not only unnecessary but is
      contraindicated since it may cause secondary hyperoxaluria (increased intestinal
      oxalate absorption) and osteopenia (negative calcium balance). On the other hand,
      overconsumption of animal protein (meat, poultry, fish) induces more pronounced
      hyperoxaluria and hypocitraturia and contributes to an overall negative calcium
      balance. It is, however, only by the interplay of "bad" dietary habits with
      underlying abnormalities such as up-regulation of calcitriol production,
      incomplete renal tubular acidosis or defective macromolecular crystallization
      inhibitors, that people become recurrent calcium renal stone formers.

PMID- 8571097
TI  - Renoprotection in diabetes. With special reference to insulin-dependent patients.
AB  - Diabetic patients developing nephropathy go through several stages of renal
      disease, moving from normo- to micro- to macroalbuminuria. Microalbuminuria is
      defined as urinary albumin excretion between 20-200 micrograms/min; lower values
      are designated normoalbuminuria and higher values macroalbuminuria. Only with
      macroalbuminuria does glomerular filtration rate (GFR) fall consistently. The
      main intermediary end-points are reduction or prevention of micro
      /macroalbuminuria, prevention or reduction of fall in GFR (stronger end-point),
      with postponement of end-stage renal disease as a final end-point. Good metabolic
      control can prevent or postpone the development of microalbuminuria, the earliest
      sign of diabetic renal disease. The ideal therapeutic window may be HbA1C between
      7 and 8.5% (mean reference value 5.5%). Thus, efforts should focus on obtaining
      the best possible control before the onset of microalbuminuria without disturbing
      hypoglycemia. In patients with microalbuminuria, blood pressure starts to
      increase and early antihypertensive treatment becomes important. Good glycemic
      control may be difficult to achieve. With overt nephropathy, defined as clinical
      proteinuria, a relentless decline in GFR occurs, unless patients are carefully
      treated with antihypertensive agents and good metabolic control is still
      important. Fall rate in GFR may be reduced from 12-->3 ml/min/year. Protein
      restriction may also be of interest, but a clear beneficial effect of optimized
      diabetes care is more difficult to document in clinical trials. However HbA1C of
      less than 8% is associated with slow regression. Early screening is recommended,
      with emphasis on testing for albuminuria, including microalbuminuria, along with
      careful control of glycemia and blood pressure.

PMID- 8571098
TI  - Blood pressure lowering for the primary and secondary prevention of coronary and
      cerebrovascular disease.
AB  - An overview of the 17 completed randomised trials of antihypertensive treatment
      demonstrates that a 5-6 mm Hg reduction in DBP reduced stroke risk by 38% (SD 4)
      and CHD risk by 16% (SD 4). These results indicate that a few years' treatment
      with diuretic- or beta-blocker-based therapy produces most or all of the long
      term stroke avoidance and much of the long-term CHD avoidance that would be
      predicted from observational epidemiological studies, given the blood pressure
      reductions that were achieved in the trials. The relative risk reductions were
      similar in trials of older and younger patients, although the absolute reduction
      in events was more than twice as great in the trials in older patients. From
      these results it can be estimated that in fully compliant patients at similar
      risk of vascular disease to those included in the trials, antihypertensive
      treatment for 5 years would prevent one major vascular event among every 20 older
      patients and one major vascular event among every 60 younger patients. Obviously
      the benefits of treatment will be greater among those at higher risk than the
      patients included in the previous trials. The greatest benefits are likely to be
      achieved in those with a history of vascular disease since their risk of future
      events is particularly high. Among such patients it is possible that blood
      pressure reduction will confer worthwhile benefits in those without hypertension,
      as well as those with hypertension. It is also possible that the benefits of
      treatment will be determined by the size of the blood pressure reduction and by
      the choice of the anti-hypertensive agent. However, each of these possibilities
      requires confirmation in large scale randomised controlled trials.

PMID- 8571099
TI  - [The cardiological progression under scrutiny of medicometrics. The case for
      cardiovascular prevention].
AB  - The utility of a new global approach to public health planning, "medicometry", is
      demonstrated using the example of cardiovascular prevention with its costs and
      benefits. Although cost-benefit analyses have become plethoric in recent years,
      they do not give the answers to the right questions asked by a society concerned
      by the explosion of investments in health care. Medicometry illustrates the
      complexity of the choices in cardiology and proposes alternative solutions
      different from simplistic proposals for short term budget cuts. For this
      demonstration several examples are used: the monetary gains of secondary and
      primary prevention; the impact of the geographical distribution of physicians on
      medical utilization; self-control of quality; and the impact of scientific and
      technologic developments on future costs. The impact of health care choices on
      the whole of society is stressed. The global feed-back of all medical branches,
      such as cardiology, is explained taking into account quality-of-life targets and
      economic, demographic and social constraints.

PMID- 8571100
TI  - [Fetal nuchal edema in the 11th to 14th week of pregnancy--an indication of
      trisomy?].
AB  - Screening for fetal trisomies based on maternal age or on second trimester
      maternal serum screening (triple test) has not significantly reduced the rate of
      liveborn babies with Down's syndrome. Nuchal translucency measured in early
      pregnancy appears to be a promising lead in screening for trisomies. Sensitivity
      is 80% with a false-positive rate of 5%. Based on maternal age and nuchal
      translucency thickness, the introduction of this method has provided promising
      results.

PMID- 8571101
TI  - [Is textbook knowledge of ultrasonography also valid in emergency admission?].
AB  - Textbook knowledge of sonography is not immediately applicable in emergencies
      where the favourable prerequisites characterizing the standard case are often
      lacking. The question therefore arises of what textbook knowledge is also viable
      in the average emergency unit, under what circumstances and for which clinical
      questions. The answer to this differentiated question is a graded concept with
      "primary emergency sonography", "extended" and "standard sonography". The
      indications and advantages of "primary emergency sonography" in contrast to
      standard procedure are discussed in detail. The key to success depends on
      meticulous introduction and training, strict compliance with indications and
      principle, and rigorous surveillance by an experienced ultrasonic specialist. In
      addition further scientific examination of the concept is necessary.

PMID- 8571102
TI  - [Severe aortic stenosis without left-ventricular hypertrophy: associated
      variables and prognosis following aortic valve replacement].
AB  - The purpose of the present study in patients with severe aortic stenosis was to
      assess prevalence, predictors and course after aortic valve replacement in
      patients without left ventricular hypertrophy according to echocardiographic mass
      criteria (LVH). 90% had LVH compared with 10% without. The following variables
      were associated with absence of LVH: younger age, low body surface area, and
      increased cardiac index. In patients with LVH, ventricular adaptation following
      aortic valve replacement was adequate more often than in those without. Six-month
      mortality following aortic valve replacement was insignificantly lower in
      patients with LVH (7.6%) than in those without it (12.5%, p = 0.10).

PMID- 8571103
TI  - [Mumps: efficacy of booster immunization].
AB  - 10 children aged 15 years, who presented with anti-mumps antibodies of < 3 PEI
      (Paul Ehrlich Institute) despite documented mumps vaccination in the past, were
      boosted with Triviraten Berna (Rubini mumps strain) and the antibody response was
      assessed after 7, 28 and 90 days. All 5 children boosted with the same vaccine
      (Rubini mumps strain) had a titer rise as early as day 7 persisting for 3 months.
      The 4 children primed with the Jeryl Lynn mumps strain showed a primary immune
      response, i.e. a rise of the antibody titer after 28 days only, which did not
      persist well. The child originally primed with the Urabe mumps strain did not
      show any significant immune response on day 28, which means a negative result.
      Children apparently susceptible to mumps cannot be differentiated from immune
      children by measurement of antibody titers. Reexposure to the homologous vaccine
      virus elicited a persisting immune response: however, revaccination with a
      heterologous vaccine virus elicited an immune response directed against different
      antigenic epitopes, followed by limited persistence of circulating antibodies.
      The efficacy of a second dose of mumps vaccine was demonstrated in 9/10 children.
      Only by using a two-dose immunization schedule is it possible to effectively
      avoid the occasionally serious complications of this viral infection, as has been
      achieved in Finland.

PMID- 8571104
TI  - [Problems in the diagnosis and therapy of lymph node tuberculosis in HIV-negative
      patients].
AB  - Tuberculosis is the world's foremost cause of death from a single infectious
      agent in adults. During the past decade the nature and magnitude of the problem
      of tuberculosis have dramatically changed. Much of what physicians have learned
      about this disease is no longer true and tuberculosis has become a new entity.
      Migration from developing areas with a high prevalence of tuberculosis to
      industrialized countries, and the problem of HIV infection, have introduced new
      components to the epidemiology. We report three cases of young immigrants with
      lymph node tuberculosis. One patient was successfully treated with the usual 9
      month-regimen. The other 2 patients, however, developed new lymph nodes or
      enlargement of existing nodes during treatment. They underwent further
      examinations, including surgical biopsies, because of diagnostic uncertainty
      (tuberculosis, superinfection or lymphoma). Finally the 2 patients were
      successfully treated with antituberculous agents for 12 and 15 months. These
      cases prompted a review of the literature and a reevaluation of the management of
      lymph node tuberculosis, including the value of surgical biopsy in the diagnosis
      of tuberculous lymphadenitis. We conclude that selective surgical biopsies should
      be recommended for differential diagnosis of tuberculous lymphadenitis.
      Histological examination (caseating epitheloid cell granulomas and giant cell
      formation) and microbiological examination (Ziehl-Neelsen staining and culture of
      native material) should be performed. Newer methods, such as amplification and
      detection of mycobacterial DNA, are rapid and sensitive tests helpful for
      diagnosis. Lymph nodes may increase in size and new nodes may appear both during
      and after chemotherapy, without indicating a failure of treatment or relapse. The
      usual treatment is a 9-month-regimen with rifamipicin, isoniazid, pyrazinamid and
      ethambutol. Prolonged or modified regimens are, however, necessary in some
      individuals.

PMID- 8571105
TI  - [Heparin-induced thrombocytopenia. Results from the Comprehensive Hospital Drug
      Monitoring (CHDM) Bern/St. Gallen].
AB  - Of 23,520 consecutive hospitalizations from 1980-1988 (corresponding to 16,628
      individual patients) in three departments of general internal medicine, 8261 were
      treated with heparin. All observations of patients displaying a probable,
      possible or questionable relationship of thrombocytopenia to heparin
      (administered i.v. or subcutaneously) were electronically collected by the CHDM
      program, revised on the basis of the primary case records and selected by
      standardized criteria. 13 of the 8261 patients exposed to heparin were considered
      to have a probable or possible HIT, corresponding to a frequency of 0.157%. In
      two of them severe thrombocytopenia was observed (corresponding to 0.024%)
      accompanied in one case by a white clot syndrome. Thrombocytopenia was defined as
      a platelet value below 100 x 10(9)/l and severe thrombocytopenia as one below 30
      x 10(9)/l. In the literature we found slight, asymptomatic thrombocytopenia in <
      or = 1-8% of heparin treated patients. Our result of 11 out of 8261
      (corresponding to 0.133%) is low, partly because the thrombocyte count was not
      controlled systematically, the heparin used was mainly produced from swine
      intestinal mucosa, and no antibody tests had been carried out. To prevent severe
      thrombocytopenia from heparin we propose monitoring the platelet count if the
      treatment is to be continued for more than 5 days. The newer low molecular weight
      heparins, all of swine origin, are much safer compared to the traditional
      preparations in regard to risk of HIT and white clot syndrome.

PMID- 8571106
TI  - [Chronic hepatitis B infection and liver failure following kidney
      transplantation].
AB  - Chronic liver diseases, especially due to chronic hepatitis B virus infection,
      are among the leading causes of late mortality in renal transplant recipients. We
      report on 4 HBsAg-positive patients observed over a period of 8 years, who were
      free of symptomatic liver disease for 7-19 years after renal transplantation and
      died within a few days of acute hepatic failure. The cases presented document the
      prognostic relevance of chronic hepatitis B virus infection in renal transplant
      recipients and illustrate that an asymptomatic HBsAg carrier state can evolve
      within a very short time to fatal liver disease.

PMID- 8571107
TI  - [Scientific raisins from 127 years SMW (Swiss Medical Weekly). Hemolytic-uremic
      syndrome: bilateral kidney cortex necrosis in acute acquired hemolytic anemia.
      1925].

PMID- 8571108
TI  - [Compliance with nasal positive pressure (CPAP) in obstructive sleep apnea
      syndrome].
AB  - Continuous positive airway pressure (CPAP) is the treatment of first choice for
      obstructive sleep apnea syndrome (OSAS). The effect of this treatment is highly
      dependent on patient compliance. To identify factors associated with compliance,
      a questionnaire was sent to 53 patients with OSAS for whom CPAP treatment had
      been prescribed. Response rate was 96%. 45 of 51 patients (88%) stated they had
      been on CPAP for a period of 30 to 2340 (median 292) days. 43 of the 51 patients
      (84%) who used CPAP regularly, defined as at least 4 hours nightly on 5 nights
      per week, were considered as compliant with the prescribed treatment. They did
      not differ from non-compliant patients either in initial symptom score or in
      apnea/hypopnea index at initial presentation. The most consistent factor
      associated with compliance was symptomatic improvement with CPAP. Side effects
      were more common in non-compliant patients. Symptomatic improvement during an
      initial trial with CPAP should be considered when starting definitive treatment,
      in order to optimize compliance.

PMID- 8571109
TI  - [Routine immunization of infants in the Canton of Zurich].
AB  - At present there is a shortage of data regarding the rate of routine immunization
      in Swiss children. To address this deficit, a representative cross sectional
      study was conducted in the Canton of Zurich with 210 children aged between 24 and
      36 months. Data was taken from the individual official vaccination certificates.
      178 vaccination certificates (55.1% female and 44.9% male) were evaluated,
      corresponding to a response rate of 84.8%. With children of foreign
      nationalities, the response rate was 66.7%, whereas the response rate of Swiss
      children was 90.6% (p < 0.001). The response rate of children of a European
      nationality outside the European Union was especially poor (33.3%). The
      immunization rate with three doses of diphtheria, tetanus and poliomyelitis
      vaccines was 99.4%, and that of the pertussis vaccine was 93.3%. With the
      vaccines for measles, mumps and rubella the rates were 80.3%, 78.1% and 77.5%
      respectively. Vaccination rate against Haemophilus influenzae type B was 74.7%
      with two doses, and 61.2% with three doses. The timing and the number of doses of
      the vaccines used for infants in the Canton of Zurich were satisfactory. However,
      the vaccination rate for measles, mumps and rubella is inadequate. Attention
      should be paid to this problem and also to possible insufficient care of foreign
      children.

PMID- 8571111
TI  - [Medico-ethical directives on the medical care of patients at the end of life or
      suffering extreme cerebral disorders. Swiss Academy of Medical Sciences].

PMID- 8571110
TI  - [Cardiology 1995].
AB  - Rapid progress in the field of cardiology calls for an almost continuous update
      on latest developments. In particular, this is the case with respect to
      indications for diagnostic and therapeutic interventions. The present
      contribution deals with some topics in this area. The first article elaborates on
      the theme of which diagnostic test is indicated, under what circumstances, and
      for which patient. Technical improvements in the surgical practice of coronary
      revascularization are discussed in the light of better therapeutic results.
      Unsolved questions of percutaneous dilatation (PTCA) are critically reviewed in a
      third article. Current problems in surgical treatment of valvular heart disease
      are dealt with in the fourth report. Finally, the enormous progress in pacemaker
      medicine that has accumulated since the world-wide first implant in 1959 by A.
      Senning is summarized in the last contribution.

PMID- 8571112
TI  - [SMW 100 years ago. Swiss Medical Weekly (Correspondence paper for Swiss
      Physicians) 1896; 26:1-2].

PMID- 8571113
TI  - [Acute hepatic porphyria and its neurological syndrome].
AB  - Certain of the hepatic porphyrias are classified as belonging to the acute
      hepatic prophyrias, namely acute intermittent porphyria (AIP), variegate
      porphyria (VP), hereditary coproporphyria (HCP) and ALA-dehydrase deficiency. The
      common feature of all acute hepatic porphyrias is the sudden onset of
      neurological symptoms. The whole syndrome consists of acute abdominal pain crises
      with autonomic dysfunction, global or focal central nervous system involvement
      and a predominantly motor polyneuropathy. Mono- or oligosymptomatic
      manifestations of acute porphyrias occur and are probably underestimated. The
      laboratory diagnosis of porphyria depends on the measurement of porphyrin
      precursors in urine, whereas the measurement of porphyrins in urine and feces is
      essential for evaluation of the porphyria type. Enzyme measurements are used to
      identify asymptomatic family members whose quantitative excretions of porphyrins
      are normal. At present the pathogenesis of neurological manifestations of acute
      porphyrias remains an unsettled question. The major hypotheses are discussed in
      this paper. The most important precipitating factor in acute hepatic porphyrias
      is drug ingestion. As many new drugs have not been in use for sufficiently long
      periods to assess their porphyrogenic activity, it is safer to avoid drugs in
      patients with porphyria. The most effective treatment of porphyria attacks is the
      administration of heme. Among the porphyria patients with epileptic seizures
      requiring antiepileptic medication, treatment with bromides should be taken into
      consideration.

PMID- 8571114
TI  - Genetics and race.

PMID- 8571115
TI  - Publicizing the value of basic research.

PMID- 8571116
TI  - Oxidative stress and apoptosis in HIV infection.

PMID- 8571117
TI  - Clinical promise, ethical quandary.

PMID- 8571118
TI  - Overhauling AIDS research: views from the community.

PMID- 8571119
TI  - Fertile results: bringing up baby (eggs)

PMID- 8571120
TI  - New virus variant killed Serengeti cats.

PMID- 8571121
TI  - The future of the behavioral and social sciences.

PMID- 8571122
TI  - Ion channels: opening the gate.

PMID- 8571123
TI  - Unscrambling color vision.

PMID- 8571124
TI  - Lysosomal degradation of ubiquitin-tagged receptors.

PMID- 8571125
TI  - Catalysis of amide proton exchange by the molecular chaperones GroEL and SecB.
AB  - Hydrogen-deuterium exchange of 39 amide protons of Bacillus amyloliquefaciens
      ribonuclease (barnase) was analyzed by two-dimensional nuclear magnetic resonance
      in the presence of micromolar concentrations of the molecular chaperones GroEL
      and SecB. Both chaperones bound to native barnase under physiological conditions
      and catalyzed exchange of deeply buried amide protons with solvent. Such exchange
      required complete unfolding of barnase, which occurred in the complex with the
      chaperones. Subsequent collapse of unfolded barnase to the exchange-protected
      folding intermediate was markedly slowed in the presence of GroEL or SecB. Thus,
      both chaperones have the potential to correct misfolding in proteins by
      annealing.

PMID- 8571126
TI  - Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small
      GTPase Rho.
AB  - The Rho guanosine 5'-triphosphatase (GTPase) cycles between the active guanosine
      triphosphate (GTP)-bound form and the inactive guanosine diphosphate-bound form
      and regulates cell adhesion and cytokinesis, but how it exerts these actions is
      unknown. The yeast two-hybrid system was used to clone a complementary DNA for a
      protein (designated Rhophilin) that specifically bound to GTP-Rho. The Rho
      binding domain of this protein has 40 percent identity with a putative regulatory
      domain of a protein kinase, PKN. PKN itself bound to GTP-Rho and was activated by
      this binding both in vitro and in vivo. This study indicates that a serine
      threonine protein kinase is a Rho effector and presents an amino acid sequence
      motif for binding to GTP-Rho that may be shared by a family of Rho target
      proteins.

PMID- 8571127
TI  - Identification of a putative target for Rho as the serine-threonine kinase
      protein kinase N.
AB  - Rho, a Ras-like small guanosine triphosphatase, has been implicated in
      cytoskeletal responses to extracellular signals such as lysophosphatidic acid
      (LPA) to form stress fibers and focal contacts. The form of RhoA bound to
      guanosine triphosphate directly bound to and activated a serine-threonine kinase,
      protein kinase N (PKN). Activated RhoA formed a complex with PKN and activated it
      in COS-7 cells. PKN was phosphorylated in Swiss 3T3 cells stimulated with LPA,
      and this phosphorylation was blocked by treatment of cells with botulinum C3
      exoenzyme. Activation of Rho may be linked directly to a serine-threonine kinase
      pathway.

PMID- 8571128
TI  - Enhanced perception of illusory contours in the lower versus upper visual
      hemifields.
AB  - The visual world consciously perceived is very different from the spatial array
      of photo-receptor activation present on our retinae; it is composed of segregated
      surfaces, organized into distinct objects. An important component of this
      organizational process, the segmentation of an image into figures and background,
      is shown to be performed much better in the lower visual field. This finding is
      demonstrated by the performance in two tasks that involve the perception of
      illusory contours. This asymmetry indicates a neural specialization that may be
      related to the anatomical discontinuity along the representation of the
      horizontal meridian in extrastriate visual cortex.

PMID- 8571129
TI  - Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a
      K+ channel.
AB  - Quaternary ammonium blockers inhibit many voltage-activated potassium (K+)
      channels from the intracellular side. When applied to Drosophila Shaker potassium
      channels expressed in mammalian cells, these rapidly reversible blockers produced
      use-dependent inhibition through an unusual mechanism--they promoted an intrinsic
      conformational change known as C-type inactivation, from which recovery is slow.
      The blockers did so by cutting off potassium ion flow to a site in the pore,
      which then emptied at a rate of 10(5) ions per second. This slow rate probably
      reflected the departure of the last ion from the multi-ion pore: Permeation of
      ions (at 10(7) per second) occurs rapidly because of ion-ion repulsion, but the
      last ion to leave would experience no such repulsion.

PMID- 8571130
TI  - Horizontal cells of the primate retina: cone specificity without spectral
      opponency.
AB  - The chromatic dimensions of human color vision have a neural basis in the retina.
      Ganglion cells, the output neurons of the retina, exhibit spectral opponency;
      they are excited by some wavelengths and inhibited by others. The hypothesis that
      the opponent circuitry emerges from selective connections between horizontal cell
      interneurons and cone photoreceptors sensitive to long, middle, and short
      wavelengths (L-, M-, and S-cones) was tested by physiologically and anatomically
      characterizing cone connections of horizontal cell mosaics in macaque monkeys. H1
      horizontal cells received input only from L- and M-cones, whereas H2 horizontal
      cells received a strong input from S-cones and a weaker input from L- and M
      cones. All cone inputs were the same sign, and both horizontal cell types lacked
      opponency. Despite cone type selectivity, the horizontal cell cannot be the locus
      of an opponent transformation in primates, including humans.

PMID- 8571131
TI  - Molecular detection of primary bladder cancer by microsatellite analysis.
AB  - Microsatellite DNA markers have been widely used as a tool for the detection of
      loss of heterozygosity and genomic instability in primary tumors. In a blinded
      study, urine samples from 25 patients with suspicious bladder lesions that had
      been identified cystoscopically were analyzed by this molecular method and by
      conventional cytology. Microsatellite changes matching those in the tumor were
      detected in the urine sediment of 19 of the 20 patients (95 percent) who were
      diagnosed with bladder cancer, whereas urine cytology detected cancer cells in 9
      of 18 (50 percent) of the samples. These results suggest that microsatellite
      analysis, which in principle can be performed at about one-third the cost of
      cytology, may be a useful addition to current screening methods for detecting
      bladder cancer.

PMID- 8571132
TI  - Expression of a Plasmodium gene introduced into subtelomeric regions of
      Plasmodium berghei chromosomes.
AB  - Targeted integration of exogenous DNA into the genome of malaria parasites will
      allow their phenotype to be modulated by means of gene disruption or the stable
      expression of foreign and mutated genes. Described here is the site-specific
      integration through reciprocal exchange, and subsequent expression, of a
      selectable marker gene into the genome of the pathogenic, bloodstage forms of the
      rodent malaria parasite Plasmodium berghei. Stable integration of a single copy
      of the marker gene (retained for more than 70 generations in the absence of drug
      pressure) into a nontranscribed subtelomeric repeat array of different
      chromosomes was observed. Expression of the gene within the subtelomeres
      indicated that the previously recorded absence of transcription in these regions
      could be due to a corresponding absence of genes rather than active silencing
      mechanisms.

PMID- 8571133
TI  - IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF
      alpha- and obesity-induced insulin resistance.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin
      resistance in obesity and diabetes through its ability to decrease the tyrosine
      kinase activity of the insulin receptor (IR). Treatment of cultured murine
      adipocytes with TNF-alpha was shown to induce serine phosphorylation of insulin
      receptor substrate 1 (IRS-1) and convert IRS-1 into an inhibitor of the IR
      tyrosine kinase activity in vitro. Myeloid 32D cells, which lack endogenous IRS
      1, were resistant to TNF-alpha-mediated inhibition of IR signaling, whereas
      transfected 32D cells that express IRS-1 were very sensitive to this effect of
      TNF-alpha. An inhibitory form of IRS-1 was observed in muscle and fat tissues
      from obese rats. These results indicate that TNF-alpha induces insulin resistance
      through an unexpected action of IRS-1 to attenuate insulin receptor signaling.

PMID- 8571135
TI  - [An evangelium vitae in the perspective of a health ministry].

PMID- 8571134
TI  - Plasma viral load, CD4+ cell counts, and HIV-1 production by cells.

PMID- 8571136
TI  - [IV. World Conference on Women].

PMID- 8571137
TI  - [Manifestation of independent and interdependent nursing interventions].

PMID- 8571138
TI  - [All life needs love].

PMID- 8571139
TI  - [Organ transplantation is everyman's responsibility].

PMID- 8571140
TI  - [How to teach asthma control].

PMID- 8571141
TI  - [The nurse as psychotherapist. A dynamic perspective of the development of
      nursing care].

PMID- 8571142
TI  - [An organized sector mobilized against AIDS].

PMID- 8571144
TI  - [The Catholic church and the treatment of pain].

PMID- 8571143
TI  - [How to evaluate pain in the aged as to their capacity to express an altered
      state].

PMID- 8571145
TI  - What is this news on the menstrual cycle and premenstrual syndrome? Introduction.

PMID- 8571146
TI  - The premenstrual syndrome: a brief history.
AB  - This paper describes the origins and development of the modern concept of
      premenstrual syndrome (PMS). Symptoms associated with the premenstrual phase of
      the menstrual cycle have been acknowledged by physicians and in the general
      culture for little more than 60 years, while the notion that they define a
      clinical syndrome is exactly 40 years old. These symptoms are experienced as
      being primarily psychological (with emotional, somatic and behavioural
      components), their aetiology is as yet not known, their prevalence varies widely
      across different cultural groups, and they appear to respond to inactive placebos
      as effectively as to active preparations. However, the empirical basis for PMS is
      unclear, and the very use of the term 'syndrome' in this context has a number of
      connotations about which at least some researchers are exceedingly sceptical.

PMID- 8571147
TI  - Stress responsivity in exercisers and non-exercisers during different phases of
      the menstrual cycle.
AB  - It has been suggested that, premenstrually, women are more vulnerable to the
      effects of stress. It has also been proposed that the fitter the individual is,
      the less the body responds to, and the more quickly it recovers from, a stressful
      experience. The present study investigated whether premenstrual sensitivity to a
      stressful laboratory task would be attenuated in women who exercised. Responses
      to the task across the menstrual cycle were studied in 20 women who exercised
      regularly and 20 women who were sedentary. Heart rate and blood pressure as well
      as subjective mood responses were measured in each of three phases: premenstrual,
      menstrual and postmenstrual. Exercising and sedentary women differed in
      sensitivity to stress: heart rate responsivity to stress was less in exercisers,
      but mood fluctuation was greater. Menstrual cycle phase, by contrast, influenced
      general levels of heart-rate and mood, but did not affect responsivity to stress
      or performance. These findings suggest that the menstrual cycle and physical
      exercise have independent effects on cardiovascular and emotional state.

PMID- 8571148
TI  - The menstrual cycle, science and femininity: assumptions underlying menstrual
      cycle research.
AB  - This paper examines the relationship between popular knowledge of menstruation
      and scientific research. It suggests that despite evidence to indicate that pre
      menstrual cognitive, behavioural and emotional 'impairment' is relatively rare,
      the population notion that PMS routinely affects many women adversely is
      difficult to displace. It concludes that mainstream menstrual cycle research is
      subject to the influence of misogynist mythology upheld as staunchly by women
      influenced by patriarchy as by men. Reasons are suggested which lie in the
      differential power of claims to knowledge.

PMID- 8571149
TI  - The menstrual cycle and the well being of women.
AB  - The concept of premenstrual syndrome (PMS) is considered and found wanting. The
      problems which are presented under the heading of PMS, however, are important and
      need better understanding A three factor model to account for such problems is
      presented. The three factors are (i) menstruation, problems with which may
      influence mood and well being premenstrually as well as during menstruation; (ii)
      the timing factor, linked to the normal hormonal cycle and producing cyclical
      variability in certain aspects of central nervous system (CNS) function; and
      (iii) the vulnerability factor, which is not a function of the menstrual cycle,
      but which involves other characteristics which result in some women reacting to
      the first two factors adversely. Evidence is presented that the mood changes
      which commonly occur perimenstrually are linked to cycle-related alterations in
      serotonergic activity in the CNS, and premenstrual food craving may be a marker
      of such alterations. The term 'menstrual cycle related problems' is offered as a
      preferable alternative to 'premenstrual syndrome'.

PMID- 8571150
TI  - Theory and methodology in premenstrual syndrome research.
AB  - Premenstrual Syndrome (PMS) is a controversial and ill-defined phenomenon, the
      aetiology of which remains an enigma, despite considerable research effort. In
      this paper, four meta-theoretical approaches to PMS are described and evaluated.
      Approaches to PMS can be criticised on three inter-related grounds. They have
      failed to describe women's experiences in detail before explaining them; they
      have not placed experience within its socio-cultural context; and they have
      assumed a linear relationship between biology or culture and behaviour. Future
      research can address these issues in two ways. Biopsychosocial models of PMS may
      integrate a variety of approaches and improve our understanding of individual
      experiences but are unlikely to offer new insights into the phenomenon of PMS.
      These are more likely to emerge from anthropological and sociological studies
      which question the cultural and individual meaning of PMS.

PMID- 8571151
TI  - Increased socioeconomic differences in mortality in eight Spanish provinces.
AB  - In Spain, the study of socioeconomic differences in mortality has been limited by
      the fact that death certificates often do not include complete information on
      occupation. In this study, we chose those geographic areas with the highest
      quality information on occupation of the deceased in order to study socioeconomic
      differences in mortality from various causes of death. We used information from
      the death certificates of males who died between 30 and 64 years of age in eight
      Spanish provinces to compare mortality from the leading causes of death in
      professionals and managers (group I) and in manual laborers (group II) in 1980-82
      and 1988-90. In each period the standardized mortality ratios (SMRs) were higher
      in group II, except for ischaemic heart disease during the first period, and
      cancer of the colon and rectum in both, although in the latter case the
      differences were not statistically significant. The ratio between the SMR from
      all causes in group II and group I was 1.27 in 1980-82, and 1.72 in 1988-90; for
      cancer of the colon and rectum the ratio went from 0.98 to 0.84, and for
      ischaemic heart disease, from 0.80 to 1.31. Except for cancer of the colon and
      rectum, which resulted in higher mortality in occupational group I, the excess
      mortality in occupational group II increased between the first and second period.
      The relation between socioeconomic level and mortality for ischaemic heart
      disease was reversed, a phenomenon similar to that which took place in the 1960s
      and 1970s in the developed countries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8571152
TI  - Health of migrants and migrant health policy, The Netherlands as an example.
AB  - In The Netherlands, as in many other countries, many studies have addressed the
      health situation of migrant groups. After a discussion on methodological pitfalls
      in migrant studies, the article reviews the most important results. The data show
      that there are differences in the health status and mortality patterns between
      migrant groups and the indigenous population. Most, but not all, of the
      differences are in disfavour of ethnic groups. Possible determinants of these
      differences are evident in socio/cultural, genetic and socio-economic factors. A
      model is presented that demonstrates the relation between these factors and
      health and disease. Implications for research and for health policy are
      discussed.

PMID- 8571153
TI  - No real progress towards equity: health of migrants and ethnic minorities on the
      eve of the year 2000.
AB  - The paper reviews the available evidence on access to health care and two health
      outcomes, perinatal mortality and accident/disability, for migrant and ethnic
      minorities in selected receiving industrialized countries. The health of these
      communities is analyzed using the entitlement approach, which considers health as
      the product of both the individual's private endowments and the social
      environment he or she faces. Migrants, especially first and second generations,
      and ethnic minorities often have reduced entitlements in receiving societies. Not
      only are they exposed to poor working and living conditions, which are per se
      determinants of poor health, but they also have reduced access to health care for
      a number of political, administrative and cultural reasons which are not
      necessarily present for the native population. The paper argues that the higher
      rates of perinatal mortality and accidents/disability observed in many migrant
      groups compared to the native population are linked to their lower entitlements
      in the receiving societies. Policies aimed at reducing such health gaps need to
      be accompanied by a more general effort to reduce inequalities and to promote
      full participation of these groups in the mainstream of society.

PMID- 8571154
TI  - Impact of user charges on vulnerable groups: the case of Kibwezi in rural Kenya.
AB  - The Government of Kenya introduced user fees for inpatient and curative
      outpatient care at its hospitals and health centres in December 1989. Children
      under five years old and those judged by the health staff to be indigent were
      among the groups exempted from fees. In September 1990, outpatient registration
      fees were removed, but other fees were retained. This paper describes the effects
      of these policy changes on the use of health services in Kibwezi division, a poor
      rural area. It focuses particularly on the impact of the fees on access to care
      by children and the poor. The assessment is based on attendance data from
      government health facilities and on a longitudinal household survey of health
      care utilization, which covered the nine months during which all fees were
      charged and two months following the removal of the registration fees. Attendance
      at government fee-charging health facilities for both outpatient and inpatient
      care was lower during the period when full fees were charged than during the same
      months of the previous year. Outpatient attendances rose again when the
      registration fees were lifted. The study households reported lower levels of
      utilization of public hospitals and health centres when full fees were in force
      than during the period after the registration fees were lifted. The pattern of
      utilization by young children, who were exempted from fees, mirrored that of the
      rest of the population, suggesting that they were not fully protected from the
      adverse effects of fees. The poorest households made much less use of the fee
      charging government facilities than the better-off households.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8571155
TI  - The social life of bonding theory.
AB  - 'Bonding' as a crucial factor of the early post-partum entered obstetric and
      paediatric practice after the publication of Maternal and Infant Bonding in 1976
      by Klaus and Kennell. The concept has held its place since, as witnessed by
      medical textbook accounts of it, and the perception of 'instantaneous bonding' as
      a vital component of the ideal birth experience has dominated media
      representations of childbirth and, until very recently, feminist writing. Only
      during the last few years has this literature taken into account research
      findings concerning the guilt and anxiety experienced by women whose expectations
      regarding 'bonding' are not realised. While it is now generally acknowledged that
      maternal attachment develops over an extended period of time, 'bonding' as used
      extensively in both popular and scientific literature conflates a wide range of
      meanings and blurs the boundaries between process and outcome. This facilitates
      the entry of ideological elements into a field which is, by its very nature,
      deeply significant for human experience. We therefore argue for a continuing
      critical appraisal of the role of 'bonding' in both general and scientific
      research.

PMID- 8571156
TI  - Research on lifestyles and health: searching for meaning.
AB  - This paper is based on an alternative approach to standard quantitative analyses
      in research on behavior and health. Theory and methods focused on the elaboration
      of complex situational and behavioral influences on health are used in secondary
      analyses of data from a population health survey in Spain. Findings showing
      fundamental differences in the relationships among the behavioral and health
      variables within various age, gender and social groups illustrate the importance
      of studying interacting influences in relevant subgroups of the population. Quite
      meaningful findings can be hidden in behavioral research limited to identifying
      global statistical correlations in cross-sectional and longitudinal data. The
      impact that statistical methods can have on the findings from analyses that are
      not guided by theory and logic based on substantive questions derived from the
      research literature is discussed. The results point to the need to study patterns
      of behavior in their contexts of occurrence in research on lifestyles and health.

PMID- 8571157
TI  - Public health crises of cities in developing countries.
AB  - During the decade and a half after Alma Ata hundreds of projects were started in
      developing countries to implement the principles of PHC and start community based
      health care programs in the rural areas of developing countries. Until the past
      five years urban health was not seen as a special health problem. Population
      pressure in the rural areas has created shortages of land, food and employment
      opportunities. These forces have generated major population movements to the
      urban centres. The population movements have encouraged unprecedented expansion
      of urban centres. This sudden concentration of large populations in small
      geographical areas has resulted in the urban health crises of the developing
      world. The poor who live in the slum areas have no access to adequate health
      services, they experience frequent epidemics of communicable diseases like
      cholera, they live within a heavily polluted environment, and their children have
      very poor health because they are not immunized and are malnourished. The paper
      agrees with approaches which have been championed by development agencies to
      address the urban health crises. These approaches propose the reorientation of
      urban health systems to include adoption of PHC for urban health programs,
      intersectoral collaboration and extra budgetary support. The paper argues for
      further strengthening of the reorientation approach by adjusting the development
      planning model. It is proposed that the urban plan be integrated into the
      national development plan so that emerging urban health crises can receive
      special attention in resource allocation.

PMID- 8571158
TI  - [Spatial distribution of cancer incidence by anatomic site in Quebec].
AB  - Knowledge of the spatial distribution of diseases provides useful information in
      etiologic research and in implementation of preventive activities in community
      health. Spatial autocorrelation analysis is one of the various methods that
      enables to determine spatial clustering of diseases. This method has not been
      applied to lung, stomach and colon cancer in Quebec. These cancers are frequent
      and are associated with environmental factors. The objectives of the study are to
      determine spatial distribution of incidence rates of these cancer sites by sex
      and to help generate etiologic hypotheses. Community health departments (CHDs) of
      residence are considered as risk markers since their population and environment
      may be related to the selected cancer sites. Data were obtained from Quebec
      Cancer Registry. Rates were standardized by the direct method. Autocorrelation
      analysis was done through BW coefficient and Moran's coefficient I for
      correlograms. Results of standardized rates were compared to those of non
      standardized rates. Rates yielded the same results for the BW coefficient.
      Conversely, results were quite different for the correlograms. This implies that
      results from standardized rates should be kept since the age structure of CHD
      populations are different. Important variation in the level of spatial
      autocorrelation was found among the six sex-specific cancer sites. For male lung
      cancer and male stomach cancer first-order neighbouring CHDs showed similar
      incidence rates according to a geographic gradient. Female lung cancer exhibited
      spatial autocorrelation. Absence of spatial autocorrelation for colon cancer
      suggests that CHD is not the appropriate scale for study of this cancer and
      allows use of conventional epidemiologic methods. These results are discussed in
      relation to current etiologic hypotheses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8571159
TI  - Interruptive patterns in medical visits: the effects of role, status and gender.
AB  - Fifty physicians (25 female, 25 male) representing six different levels of status
      (interns, second and third year residents, fellows and junior and senior staff)
      were videotaped, each with a male and a female patient. The videotapes were coded
      for interruptive and overlapping speech, for both physician and patient. Specific
      categories were successful interruptions, partially successful interruptions,
      unsuccessful interruptions and overlaps. In addition, all instances of
      interruptive and overlapping speech were coded as a question or a statement.
      Results showed, overall, that patients engaged in significantly more interruptive
      and overlapping speech than did physicians. However, when these variables were
      analyzed separately for questions and statements, patients were found to
      interrupt more with statements, whereas physicians interrupted more with
      questions. High and low status physicians did not differ in their use of
      interruptions. The few gender differences that did emerge did not indicate a
      clear pattern of male dominance. The results showing patients to interrupt
      physicians more than the reverse suggest that interrupting may not solely be a
      behavior of the higher status person. Together the findings of this study
      challenge the notion that interruptions simply reflect dominance and/or status
      and are a behavior more often displayed by males than by females.

PMID- 8571160
TI  - 'If this is what it's doing to our washing, what is it doing to our lungs?'
      Industrial pollution and public understanding in north-east England.
AB  - An epidemiological study of the impact of industrial pollution from a cokeing
      works in north-east England on the health of a population resident nearby
      uncovered strong but localised public concern about the possible dangers of air
      pollution. This paper discusses these popular concerns in the context of
      empirical findings from the study which examined evidence of ill-health alongside
      evidence on air quality levels. The substantive issues this paper examines relate
      to local variations in popular beliefs about health risks, and the relation
      between such beliefs and measurable differences in health states and status. The
      methodological issues addressed centre on the difficulties of interpreting this
      relationship between popular beliefs and concerns, on the one hand, and health
      experience, or apparent health experience, on the other.

PMID- 8571161
TI  - Setting the agenda: does the medical literature set the agenda for articles about
      medicines in the newspapers?
AB  - The source of ideas and information on medicines most important to journalists in
      the Netherlands, and most commonly consulted by them, is known to be the
      scientific medical literature. In this study we therefore, explored the relation
      between the kind of medicines discussed in the scientific medical literature and
      those discussed in newspapers. A content analysis of scientific medical journals
      was combined with a content analysis of Dutch daily newspapers. The results show
      an agreement in the main groups of medicines discussed in the scientific medical
      literature and newspapers. In both the newspapers and the professional journals
      anti-infective medication and drugs for the central nervous system are the groups
      of medicines most frequently discussed. Although it has been suggested that 'bad
      news' is more newsworthy then 'good news', the negative consequences of the use
      of medicines received proportionally more attention in the professional
      literature than in the newspapers.

PMID- 8571162
TI  - The social network of patients with schizoaffective disorder as compared to
      healthy individuals.
AB  - The social network was evaluated by means of the self-rating scale 'Interview
      Schedule for Social Interaction' (ISSI) and semi-structured interviews in married
      patients with a DSM-III diagnosis of schizoaffective disorder (N = 17, partners,
      N = 16), married patients with diabetes (N = 10, partners, N = 10) and in married
      healthy individuals (N = 8, partners, N = 8). The two latter groups were
      comparison control groups matched for sex and age to the patients with a
      schizoaffective disorder. The scores on the ISSI and its subscales for the groups
      were compatible to those found in other Swedish studies. Patients with a
      schizoaffective disorder both experienced that they had less access to (AVAT) and
      were less satisfied with their deep emotional relations (ADAT). The same patients
      had a higher level of neuroticism as compared to the rest. The patients with a
      schizoaffective disorder had less often than the patients with diabetes been
      informed about their disease. Moreover, the partners to the patients with a
      schizoaffective disorder had not been informed about the disease and experienced
      that they had fewer social contacts (AVSI). A challenge for the professional
      network in psychiatry is to improve the information and education to families in
      which one member is struck by a schizoaffective disorder.

PMID- 8571163
TI  - Viral immunopathology. Introduction.

PMID- 8571164
TI  - Arboviruses and the central nervous system.
AB  - Arboviruses cause encephalitis by infecting neurons of the host. Virus infection
      per se may cause death or dysfunction of neurons. The severity of the virus
      effect is dependent on the virulence of the virus and the maturity of the
      infected neuron. Neurons do not directly interact with T cells since they do not
      express MHC class I or class II antigens in vivo. Other cells such as microglia
      and perivascular macrophages probably present viral antigen to activated T cells
      coming to the brain from lymphoid organs. Infection elicits a local immune
      response that is characterized by mononuclear cell infiltration and local
      production of cytokines and antiviral antibody. The cytokines are primarily
      characteristic of type 2 T cells providing B cell help and macrophage
      deactivation. Control of virus replication is effected by antibody which does not
      eliminate infected cells. Therefore, viral RNA persists in the CNS, requiring
      continuous intraparenchymal production of antiviral antibody.

PMID- 8571165
TI  - Immunopathological aspects of coronavirus infections.

PMID- 8571166
TI  - The humoral immune response in acute and chronic hepatitis B virus infection.

PMID- 8571167
TI  - Lactate dehydrogenase-elevating virus: an ideal persistent virus?

PMID- 8571168
TI  - Immunopathological mechanisms in respiratory syncytial virus disease.

PMID- 8571170
TI  - Cells and cytokines in the pathogenesis of MAIDS, a retrovirus-induced
      immunodeficiency syndrome of mice.

PMID- 8571169
TI  - The Epstein-Barr virus in autoimmunity.

PMID- 8571171
TI  - Immune conflicts in lymphocytic choriomeningitis virus.

PMID- 8571173
TI  - [Primary gastric lymphoma of the MALT type. The current knowledge on its
      etiology, therapy and prognosis].
AB  - Primary gastric lymphoma are nowadays considered as a distinct lymphoma entity.
      They are mostly classified as low or high grade malignant B-cell-lymphoma of the
      MALT (mucosa-associated lymphoid tissue). Within the gastrointestinal tract, the
      stomach is most frequently involved. In the pathogenesis of gastric lymphoma,
      Helicobacter pylori-associated gastritis plays an important conditioning role.
      Histological grading, stage and resectability of lymphoma are considered as major
      prognostic factors. Options in the therapy of gastric lymphoma are based on their
      histological grade and stage of the disease. They include surgical resection
      and/or radiotherapy for local tumor control as well as chemotherapy in the case
      of disseminated disease or high malignancy. Currently, special interest focuses
      on the effect of Helicobacter pylori eradication.

PMID- 8571172
TI  - Hepatitis B virus immunopathology.
AB  - Approximately 5% of the world population is infected by the hepatitis B virus
      (HBV) which causes a necroinflammatory liver disease of variable duration and
      severity. Chronically infected patients with active liver disease carry a high
      risk of developing cirrhosis and hepatocellular carcinoma. The immune response to
      HBV-encoded antigens is responsible both for viral clearance and for disease
      pathogenesis during this infection. While the humoral antibody response to viral
      envelope antigens contributes to the clearance of circulating virus particles,
      the cellular immune response to the envelope, nucleocapsid and polymerase
      antigens eliminates infected cells. The class I- and class II-restricted T cell
      responses to the virus are vigorous, polyclonal and multispecific in acutely
      infected patients who successfully clear the virus, and they are relatively weak
      and more narrowly focussed in chronically infected patients who do not. The
      pathogenetic and antiviral potential of the cytotoxic T lymphocyte (CTL) response
      to HBV have been demonstrated by the induction of a severe necroinflammatory
      liver disease following the adoptive transfer of HBV surface antigen-specific CTL
      into HBV transgenic mice, and by the noncytolytic suppression of viral gene
      expression and replication in the same animals by a post-transcriptional
      mechanism mediated by interferon-gamma, tumor necrosis factor-alpha and
      interleukin-2. The dominant cause of viral persistence during HBV infection is
      the development of a weak antiviral immune response to the viral antigens. While
      neonatal tolerance probably plays an important role in viral persistence in
      patients infected at birth, the basis for poor responsiveness in adult onset
      infection is not well understood and requires further analysis. Viral evasion by
      epitope inactivation and T cell receptor antagonism may contribute to the
      worsening of viral persistence in the setting of an ineffective immune response,
      as can the incomplete down-regulation of viral gene expression and the infection
      of immunologically privileged tissues. Chronic liver cell injury and the
      attendant inflammatory and regenerative responses create the mutagenic and
      mitogenic stimuli for the development of DNA damage that can cause hepatocellular
      carcinoma. Elucidation of the immunological and virological basis for HBV
      persistence may yield immunotherapeutic and antiviral strategies to terminate
      chronic HBV infection and reduce the risk of its life-threatening sequellae.

PMID- 8571174
TI  - [Endoluminal HDR brachytherapy in the palliative treatment of patients with the
      recurrence of a non-small-cell bronchial carcinoma after prior radiotherapy].
AB  - PURPOSE: The preferred primary treatment in non-small cell lung cancer is
      surgical resection. In fact, only less than 25% of patients are resectable with
      curative intent. The remaining patients are primarily treated with radiation
      therapy or combined radiochemotherapy, achieving remission rates up to 60% but 5
      year survival rates of only about 5%. Therefore an effective palliative treatment
      is important. The aim of our study was to show that using intraluminal HDR
      brachytherapy, tumor-induced bronchial obstruction and its symptoms can be
      relieved in the majority of cases. PATIENTS AND METHODS: Sixteen patients with
      recurrent previously irradiated non-small cell lung cancer were treated with
      intraluminal high dose rate iridium-192 afterloading irradiation at the
      Department of Radiotherapy and Radiation Oncology of the University of Munster
      between 1989 and 1993. There were 15 men and 1 woman with a median age of 61
      years. As a primary treatment, 50 to 60 Gy had been delivered percutaneously. The
      recurrences were treated with HDR brachytherapy using 2 to 4 applications of 5 Gy
      to 6 Gy each to a tissue depth of 0.5 cm. RESULTS: In 13 of 16 patients dyspnoea
      could be improved and in 15 of 16 patients atelectasis could be dissolved. Nine
      of 16 patients achieved a partial or complete remission evaluated by
      bronchoscopic criteria. The median period of remission was 4 months. The median
      survival time, measured from the start of therapy and analysed using the Kaplan
      Meier method, was only 9 months. As side effects, 1 pneumothorax and 1
      tracheomediastinal fistula occurred, the latter presumably related to tumor
      progression. CONCLUSION: Our results show the importance of intraluminal HDR
      brachytherapy in the palliative treatment of patients with recurrent non-small
      cell lung cancer.

PMID- 8571175
TI  - Hyperthermia--its actual role in radiation oncology. Part IV: Thermo-radiotherapy
      for malignant brain tumors.
AB  - BACKGROUND: High-grade malignant gliomas have a dismal prognosis. Only
      achievement of long-term local control improves overall survival. Conventional
      treatments have not been successful, but thermoradiotherapy appears to be a
      promising new approach to this disease. PATIENTS AND METHODS: The review
      addresses the various HT techniques applied for brain heating, the biological
      rationale and experimental studies supporting the use of heat in addition to
      radiotherapy for brain tumors. Normal brain damage exposed to heat is critically
      evaluated. Clinical trials implementing HT for tumors of the brain accumulating
      more than 400 patients are discussed. RESULTS: HT is a feasible and effective
      approach to brain tumors. Important selection criteria are tumor size (< 6 cm)
      and location (supratentorial, peripheral). Acute treatment toxicity is relatively
      low and long-term side effects are similar to those observed for RT alone. In
      some studies a high response rate and improvement of survival was achieved. Tumor
      control and survival depend on histology (anaplastic astrocytoma vs. glioblastoma
      multiforme), extent of surgery (complete vs. incomplete), tumor status (primary
      vs. recurrent), age and performance status. Satisfactory heating also correlates
      significantly with favourable treatment outcome. CONCLUSIONS: The encouraging
      results of clinical trials may be biased by favourable tumor and patient
      selection. Randomized clinical trials comparing RT alone versus combined RT-HT
      for advanced and recurrent brain tumors are justified. Part I has covered
      biological and technical fundamentals of clinical hyperthermia and has been
      published in Strahlenther. Onkol. 168 (1992), 183-190. Part II has covered
      clinical fundamentals and results in superficial tumors of clinical hyperthermia
      and has been published in Strahlenther. Onkol. 169 (1993), 633-654. Part III has
      covered clinical rationale and results in deep seated tumors and has been
      published in Strahlenther. Onkol. 171 (1995), 251-264.

PMID- 8571176
TI  - Many component model and its parameters to fractionated irradiation.
AB  - PURPOSE: In this study, a many component model has been formulated to address the
      contribution of various bio-molecules in radiation induced biological damage and
      this model is fitted to radiation isoeffect data to evaluate the parameter
      alpha/beta. MATERIAL AND METHODS: Every living cell contains a number of organic
      and inorganic molecules which may act as targets to lead radiation induced
      damage. During irradiation, many kinds of physical, chemical and biological
      products are produced which are due to active participation of aforesaid
      molecules. The many component model, hereinafter called linear-quadratic-cubic
      (LQC) model, is an attempt to provide a better mathematical formulation which
      could demonstrate the contribution of various kinds of biomolecules in biological
      effect of radiation. This model has only one independent parameter alpha/beta and
      a number of dependent parameters which are the derivatives of alpha/beta.
      RESULTS: Three methods, for testing the fit of the proposed model and deriving
      the values of alpha/beta, are employed using multifractionation isoeffect data.
      These methods, i.e. (logDm-logDn) versus (dn-dm) plot, SFe-plot and logD versus d
      plot, provide their respective values of alpha/beta as 12.50 Gy, 12.51 Gy and
      12.54 Gy for spleen. 7.41 Gy, 7.79 Gy and 7.42 Gy for kidney, 15.87 Gy, 15.09 Gy
      and 14.69 Gy for colon with 3 h interval, 12.50 Gy, 12.84 Gy and 12.45 Gy for
      colon with 12 h interval and 8.47 Gy, 8.84 Gy and 8.51 Gy for colon with 24 h
      interval. Since other parameters of the model are the derivatives of alpha/beta
      therefore can be derived using the values of alpha/beta. DISCUSSION: Graphical
      representation of afore said sets of data show that the plotted points have a
      certain amount of scattering which is not at the wider scale and can be well or
      less well described by a straight line. CONCLUSION: This model eliminates the
      shortcomings of LQ model and provides a satisfactory explanation of various
      radiobiological processes occurring during and after irradiation.

PMID- 8571177
TI  - [Can an extremely elevated radiosensitivity in patients be recognized by the in
      vitro testing of lymphocytes?].
AB  - BACKGROUND: We have examined the in-vitro radiosensitivity of lymphocytes in
      patients with extreme acute and chronic reactions after curative radiotherapy
      under the assumption of increased genetic radiosensitivity. PATIENTS AND METHODS:
      16 patients (14 females, 2 males, age 40 to 69 years) were retrospectively
      examined 1 to 108 months after radiotherapy. All had undergone definitive or
      postoperative curative radiotherapy for cancer (12 breast cancer, 2 lung, 1
      bladder, and 1 head and neck cancer). None of them had known genetic disorders
      with increased radiosensitivity. Four patients were considered as having probably
      increased radiosensitivity; they had shown poor tolerance to radiotherapy (1
      severe acute reaction with cessation of radiotherapy in bladder cancer and
      subsequent bladder shrinkage after 45 Gy, 1 acute skin reaction well above
      average with subsequent fibrosis after irradiation for regional recurrence of
      breast cancer, 1 radiation myelitis after palliative irradiation with 5 x 5 Gy
      for lung cancer, 1 severe acute reaction after mediastinal irradiation for lung
      cancer). Twelve patients were considered as having normal tolerance to
      radiotherapy. They had tolerated radiotherapy well with normal acute reactions
      and no or minimal signs of late radiation sequelae. Lymphocyte cultures were
      prepared from all patients and irradiated with 0.7 and 2 Gy, respectively; 1
      culture served as control (0 Gy). Chromosomes 1, 2, and 4 were stained using
      fluorescence in-situ hybridization (FISH) with a 3-colour-chromosome-in-situ
      suppression technique. Chromosomal breaks were counted in 200 to 1000 mitoses.
      Radiation sensitivity was expressed as radiation-induced breaks per mitoses
      corrected for breaks at 0 Gy. The probes were coded and the examiner did not know
      the clinical course. RESULTS: Significant differences in interindividual
      radiation sensitivity were detectable. The frequency of radiation-induced
      breaks/1000 mitoses ranged from 70 to 556 after 0.7 Gy and from 420 to 1210 after
      2 Gy. The 4 patients with increased clinical radiation sensitivity showed also
      increased chromosomal radiation-induced damage as compared to the 12 patients
      with normal radiation tolerance (469 +/- 103 vs. 126 +/- 79 breaks/1000 mitoses
      induced by 0.7 Gy, p = 0.0011, and 864 +/- 258 vs. 574 +/- 119 breaks/1000
      mitoses induced by 2 Gy, p = 0.019). CONCLUSIONS: Patients with increased
      clinical radiosensitivity exhibited increased chromosomal damage in lymphocytes
      in vitro measured with chromosome painting with a FISH-technique. This technique
      may be useful to detect patients with severely enhanced radiosensitivity. The
      results suggest that if radiosensitivity is abnormally elevated this may be
      present and detectable in different organs.

PMID- 8571178
TI  - [Tumor markers as prognostic factors in non-small-cell bronchial carcinoma].
AB  - PURPOSE: Considerations of different therapeutic approaches require a realistic
      estimation of the prognosis. The usefulness of tumor markers as prognostic
      indicators was evaluated by means of a multivariate analysis. PATIENTS AND
      METHODS: The data of 300 patients who had been irradiated for their primary tumor
      were analysed retrospectively. The serum concentrations of CEA, SCCA, NSE, and
      LDH were available before treatment and 3 months thereafter in a sufficient
      number of cases. The prognostic factors for survival and progression-free
      survival resulting from univariate tests were further evaluated by a Cox
      proportional-hazards model. RESULTS: The serum levels of the particular tumor
      markers were pathologically elevated in 25 to 36.5% of the cases. Their values
      correlated with the stage of the disease and separately the N-stage too. A
      normalization of increased marker levels after irradiation occurred in 37.5 to
      67% of the cases. Survival of patients with increased pretherapeutic values of
      CEA, SCCA, and LDH was significantly worse compared to those with normal values.
      In the case of a post-therapeutic return to normal levels, prognosis was
      significantly better than for those where the elevation persisted. However, after
      inclusion of all other parameters in multivariate analysis the tumor markers were
      meaningless. Karnofsky-performance status, total dose of radiotherapy, stage of
      the disease, and weight-loss evolved as independent prognostic factors for
      survival. For progression-free survival only stage of the disease was important.
      All subgroup analyses (restriction on patients with favorable prognosis) showed
      the same results. CONCLUSIONS: A prognostic importance of NSE could not be
      demonstrated. CEA, SCCA, and LDH were univariate predictors for survival and
      progression-free survival. But they proved to be dependent on the stage of the
      disease and were not confirmed as independent variables in the Cox-model. Their
      importance during the follow-up is diminished by the frequent lack of therapeutic
      approaches in the case of disease progression. Certainly a more favorable
      prognosis in case of a post-therapeutic normalization of previously elevated
      values was found.

PMID- 8571179
TI  - [The value of conventionally fractionated radiotherapy in the local treatment of
      HIV-related Kaposi's sarcoma].
AB  - BACKGROUND: During the course of AIDS, 25 to 44% of homosexual patients infected
      with the human immunodeficiency virus develop Kaposi's sarcoma. Main
      manifestation is the skin. Response rates of 80 to 100% can be achieved with
      total dosage up to 50 Gy. Nevertheless, remissions can also be attained with 20
      Gy of fractionated radiotherapy. As clinical data on low dose conventional
      fractionated radiotherapy are insufficient we analysed the response rates of an
      overall dose of 20 Gy in conventional fractionation. PATIENTS AND METHODS: From
      June 1991 to June 1993, 43 patients with 111 HIV-associated Kaposi's sarcoma of
      the skin or oral cavity were treated. Lesions were irradiated with 5 to 12 MeV
      electrons or 60Co gamma-rays. The fractionation scheme was 5 times 2 Gy/week for
      skin and endoral lesions with a total reference dosage of up to 20 Gy. Side
      effects were assessed during therapy and the therapeutic result 6 weeks after end
      of treatment. RESULTS: Thirty-eight out of 111 lesions were judged as complete
      response (CR) (34%), 61/111 as partial response (PR) (55%) and 12/111 were judged
      as no change (NC) (11%). Overall response (CR + PR) was 89%. Two patients with
      lesions of oral cavity suffered from RTOG grade-IV mucositis after 10 and 14 Gy.
      In 71/106 skin lesions (67%), radiation induced RTOG grade-1 reactions were
      observed. CONCLUSION: In patients with HIV associated Kaposi's sarcoma effective
      palliation can be achieved by means of radiotherapy with an overall dose of 20 Gy
      in conventional fractionation. Yet, the fraction of patients with complete
      responses is with 34 to 47% lower compared with doses above 20 Gy (66 to 100%).
      With reference to the reported data our results point to a dose-response
      relationship for Kaposi's sarcoma. Therefore higher total reference doses, e.g.
      30 Gy with weekly 5 times 2 Gy or 24 Gy with 5 times 1.6 Gy for mucous lesions,
      respectively, are suggested as by this mean the complete response rate can be
      doubled.

PMID- 8571180
TI  - [Do we need animal trials for the improvement of the diagnosis and therapy of
      tumors?].

PMID- 8571181
TI  - The influence of computer tomography on treatment strategies and follow-up in
      tumors of the nasopharynx and the paranasal sinuses. A retrospective study on 104
      patients.
AB  - BACKGROUND: The high value of computer tomography (CT) for detailed imaging of
      nasopharyngeal and paranasal sinus tumors is known. Less known is the influence
      of such diagnostic findings on decisions of the therapist. An analysis of this
      influence might help to compare the value of CT and MRT. PATIENTS AND METHODS: We
      performed a retrospective study on 104 treated patients with malignant tumors of
      the nasopharynx (n = 54) and the paranasal sinuses (n = 50). The study analyzed
      the influence of CT on primary tumor diagnosis, tumor staging, treatment
      decision, therapy planning, detection and time of recurrences and retreatment of
      relapses. RESULTS: Tumors of the nasopharynx: The value of CT for tumor staging
      was 76% but there was no influence on treatment decision. Radiotherapy planning
      was influenced in 37% of cases. CT for follow-up was done in 22% of cases. Most
      relapses occurred within the first 2 years. Paranasal sinus tumors: There was no
      influence of CT on primary diagnosis of the tumor. Tumor staging was influenced
      by CT in 94%, treatment decision in 44% and radiotherapy planning in 60%. CT
      control immediately after therapy was of value in 40%. Most relapses were found
      within 3 years but some in the 4th and 5th year. Some patients survived 3 to 9
      years after retreatment. CONCLUSIONS: In tumors of the nasopharynx there is less
      influence of CT on therapy strategies than diagnostic radiologists might think.
      No CT is needed for treatment decision since radiotherapy is the only choice of
      treatment. CT influenced radiotherapy planning however, in about 1/3 of our cases
      answering sufficiently the 2 main questions: tumor spread into the anterior half
      of the facial skull or involvement of the base of skull. The retreatment of
      recurrences detected by CT showed poor results. Late recurrences seem to have
      better prognosis. We recommend therefore routinely 1 basic CT 6 months after
      primary treatment followed by 1 CT yearly from the 3rd to 5th year. MRT might
      offer more diagnostic details than CT. However, at present therapy is not
      influenced much by this. Since CT is cheaper and faster, MRT could be discussed
      as additional procedure when CT presents equivocal findings and this fact could
      be decisive for therapy planning. Paranasal sinus tumors: The influence of CT on
      tumor-staging and treatment decision is high and convincing. CT helps also at
      radiotherapy planning and control of tumor response after therapy. CT has high
      value in detecting recurrences. Retreatment could control disease in some of our
      patients for 3 to 9 years. Better results could be achieved possibly with earlier
      diagnosis of recurrence. We propose therefore a basic-CT 6 months after first
      treatment and 1 CT routinely from the 2nd to 5th year. From the therapist's point
      of view we recommend CT as first imaging procedure in sinonasal tumors. MRT, more
      time- and cost consuming, should be applied when CT is equivocal and treatment
      decision could be influenced.

PMID- 8571182
TI  - [The late cardiac sequelae after mantle-field irradiation. The results in
      Erlangen's patient caseload].
AB  - PURPOSE: We have retrospectively evaluated the cardiac function in patients after
      mantle-irradiation for Hodgkin's disease. PATIENTS AND METHODS: Forty-three
      patients, mean age 39.8 +/- 13 years, who had been treated with mantle
      irradiation from 1979 through 1984 at the University of Erlangen-Nurnberg, were
      examined. All of them were in first remission at 5 to 11 years (mean 8.1 years)
      after radiotherapy (n = 24) or combined modality treatment (n = 19). Mantle
      irradiation had been administered through equally weighted anterioposterior
      posterioanterior portals with 5 fractions of 2 Gy per week up to a total
      mediastinal dose of 41.8 +/- 7 Gy (including boost). The examination program
      included anamnesis, physical examination, Doppler echocardiography and ergometry.
      Hundred and twenty-two non-irradiated volunteers and cardiological patients were
      used as control group. RESULTS: None of the patients suffered from clinical
      symptoms. Pericardial thickening was present in 26%. The left ventricular end
      systolic diameter (31.3 +/- 5.5 mm, normal value 26 to 42 mm) and the thickness
      of the left ventricular posterior wall (8.1 +/- 1.8 mm, normal value 6 to 11 mm)
      were within the normal range. The left ventricular ejection fraction was also
      normal (67.1 +/- 8% in patients versus 67.0 +/- 8% in control subjects).
      Evaluation of diastolic parameters, however, revealed significant changes. The
      isovolumic relaxation time was significantly decreased as compared to the control
      group (38.8 +/- 17 ms versus 50.8 +/- 21 ms, p < 0.05). The same we found for the
      shortening fraction (33.6 +/- 6% versus 38.1 +/- 6%, p < 0.05). The most
      significant changes were found after combined modality therapy, especially after
      radiotherapy and anthracycline-based chemotherapy. 30% of the patients were
      tachycardic (pulse > 100/min) at rest. At ergometry, the frequency of signs of
      ischemia (5%), conduction disturbances (2%), and rhythm disturbances (7%) was not
      elevated. CONCLUSIONS: In this retrospective investigation, patients after mantle
      irradiation with modern techniques showed only minimal cardiologic abnormalities
      within the first 10 years after treatment. The most sensitive parameters were the
      isovolumic relaxation times. The clinical relevance of such findings remains to
      be defined. Pathophysiologically, our findings (decreased relaxation time plus
      tachycardia) support the theory that myocardial damage after radiotherapy may
      result in subsequent increased beta-receptor density as proposed by Schultz
      Hector et al. [21] on the basis of experimental data.

PMID- 8571183
TI  - Effects of sulphur-containing compounds and X-rays on the mouse erythropoietic
      system assayed by in-vivo peripheral blood micronucleus test.
AB  - PURPOSE: The protective effect of the sulphur-containing agents, MEA (cysteamine
      HCl), AET (2-aminoethyl-isothiouronium Br.HBr), and WR-2721 (S-2/3
      aminopropylamino/ethylphosphorothioic acid) against induction of micronuclei in
      the erythropoietic system by X-rays was assessed. METHODS: The mouse peripheral
      blood micronucleus assay was applied. The frequency of micronucleated
      polychromatic erythrocytes (MNPCE) in the peripheral blood of adult male Swiss
      mice was determined 24 h after MEA, AET, or WR-2721 treatment, at a dose of 200
      mg/kg body weight, and whole-body X-ray exposure to a dose of 6 Gy. RESULTS:
      After X-irradiation of mice, the number of MNPCE was distinctly increased. MEA,
      AET, or WR-2721 administration, 15 min prior to X-irradiation resulted in a
      reduction of the X-ray-induced elevation of the frequency of micronuclei. So, the
      radioprotection of the sulphur-containing drugs against the induction of MNPCE in
      the erythropoietic system by X-rays was shown. CONCLUSION: The mouse peripheral
      blood micronucleus test can be used to screen potential radioprotective agents.

PMID- 8571184
TI  - Prognostic factors for local control in hypopharyngeal cancer treated with
      radical irradiation.
AB  - PURPOSE: We retrospectively analyzed prognostic factors for local control in
      hypopharyngeal cancer. PATIENTS AND METHODS: Twenty-five patients with
      hypopharyngeal cancer treated with radical irradiation were entered into
      analyses. Local control according to clinical T stage and subsites of hypopharynx
      were analyzed. For 8 clinical T2 patients, local control according to findings
      assessed by pretreatment CT was also evaluated. RESULTS: The 2-year local control
      rates were 40% for all, 1/2 for T1, 8/11 (73%) for T2, 1/8 (12%) for T3, and 0/4
      for T4. Two-year local control rates were 28% for pyriform sinus cancer and 66%
      for pharyngeal wall cancer. Local control analysis according to CT findings for
      patients with T2 hypopharyngeal cancer showed that patients without specified
      involvement beyond the hypopharynx or in the apex had good local control.
      CONCLUSION: Our preliminary analysis suggested that clinical T2 hypopharyngeal
      cancer patients without invasion beyond the hypopharynx or in the apex
      demonstrated on CT had favorable local prognosis when treated with radical
      irradiation.

PMID- 8571185
TI  - [The treatment of cutaneous radiation-induced fibrosis with pentoxifylline and
      vitamin E. An empirical report].
AB  - BACKGROUND: Radiation fibrosis represents a severe complication of radiation
      therapy; standardized treatment protocols are lacking so far. Surgical excision
      rarely results in complete healing. PATIENT AND METHODS: We report on a 58-year
      old female patient who developed a squamous cell carcinoma within the fibrotic
      area of the irradiation field on the right chest, resulting from a radiotherapy
      following mastectomy for breast cancer 17 years ago. After surgical excision of
      the carcinoma a combined treatment with pentoxifylline tablets (3 x 400 mg/d
      p.o.) and vitamin-E capsules (1 x 400 mg/d p.o.) was initiated. Skin thickness
      was quantified by 20 MHz-ultrasound before and during treatment. RESULTS: The
      patient noted an increasing improvement of the condition of the affected skin
      starting from 4 months. A continuing decrease of skin thickness as documented by
      20 MHz-ultrasound could be demonstrated from the 6th month on. The treatment was
      tolerated well, no side effects were observed. CONCLUSION: The data indicate a
      beneficial therapeutic effect of pentoxifylline and vitamin E on radiation
      induced fibrosis. Little is known about the mechanism of action of this combined
      treatment protocol including pentoxifylline and vitamin E. Controlled clinical
      trials should be performed to confirm this observation.

PMID- 8571186
TI  - [The behavior of the activation parameters of plasma coagulation under HDR
      afterloading therapy in patients with endometrial carcinoma].
AB  - BACKGROUND: In the radium era heparin prophylaxis was necessary to avoid
      thromboembolic events. Today with high-dose-rate (HDR) afterloading
      thromboembolic events are rare. Coagulation activation parameters were monitored
      during HDR afterloading to evaluate the necessity of heparin prophylaxis.
      PATIENTS AND METHODS: Twenty patients with uterine carcinoma and no postoperative
      tumor residuals were randomized before their first 10 Gy OD HDR-afterloading
      application. Ten patients received heparin prophylaxis, the other ten patients
      received no prophylaxis. Blood samples were taken before, immediately after, 6
      and 24 hours after HDR afterloading. D-Dimer, TAT, and F 1 + 2 were measured.
      RESULTS: No significant activation of the coagulation system was observed over
      the investigated time period and no differences have been detected between both
      groups. None of the patients of either group developed thromboembolic
      complications. CONCLUSIONS: HDR afterloading has no direct influence on the
      plasmatic coagulation system. From this point of view heparin prophylaxis does
      not seem necessary.

PMID- 8571187
TI  - [The assessment of solitary osteolytic bone lesions in breast carcinoma. A
      special case report].
AB  - BACKGROUND: Solitary bone lesions occurring 10 and more years after primary known
      breast cancer are usually declared as metastases of this tumor. However, this
      assumption is not correct. In such cases the probability of a second malignancy
      has to be concerned as well. PATIENTS AND METHODS: We report the case of a 77
      year-old woman, in whom 18 years after primary breast cancer therapy an
      osteolysis in her right radius occurred. The treatment planning was aggravated by
      the diagnostic classification of this lesion. RESULTS: The diagnostical
      differentiation between bone metastases of the known breast cancer or another
      extramammary solid cancer and a primary tumor of the bone was not possible by
      clinical and blood examination, X-ray and MRT-imaging. As the diagnostically
      decisive step a biopsy was performed proving a metastasis of the known breast
      cancer. CONCLUSIONS: This case pointed out that the diagnostical classification
      of a solitary osseous lesion exclusively based on anamnestically known primary
      cancer treated long times ago is not permissible. Before therapeutic decision is
      correctly fixed, detailed diagnostic examinations according to basic oncological
      rules are conclusively required.

PMID- 8571188
TI  - [High-precision radiotherapy for 30 low-grade gliomas: the first results].

PMID- 8571189
TI  - [DNA double-strand break repair and radiation response in human tumor primary
      cultures].

PMID- 8571190
TI  - [Preoperative regional therapy for extremity sarcoma].

PMID- 8571191
TI  - [Autologous bone marrow transplantation as early therapy for patients with
      aggressive non-Hodgkin's lymphoma].

PMID- 8571192
TI  - [Recurrent mammary carcinoma after local excision].

PMID- 8571193
TI  - [Stereotaxic convergent-beam irradiation. Initial experiences with the SRS 200
      system].
AB  - BACKGROUND: The system SRS 200 for the stereotactic convergent beam irradiation
      described in this paper has a stereotactic floor stand, which allows the high
      precision rotation of a secondary collimator around an isocenter. This system is
      used since 1991 at the University Hospital of Tubingen for the treatment of
      patients with solitary brain metastases, acoustic neurinomas and arteriovenous
      malformations. PATIENTS AND METHODS: The attainable accuracy of the mechanics and
      dosimetry was studied within the scope of extensive quality assurance measures
      during its installation and before each patients' irradiation. The individual
      treatment steps from radiotherapy planning to irradiation were evaluated by means
      of a specially developed head phantom. Since the installation of the SRS 200 a
      total of 50 patients (21 solitary brain metastases, 12 acoustic neurinomas, 17
      arteriovenous malformations) has been treated with the system. RESULTS: With 0.3
      mm +/- 0.2 mm an excellent accuracy of the target point transfer and isocenter
      stability during irradiation was attained. The difference between calculated dose
      and dosimetric control measurements was smaller than 3%. The physical accuracy,
      however, is limited by the imaging resolution (CT and digital subtraction
      angiography). Of the patients 15% with solitary brain metastases developed
      complete remission, 20% partial remission and with 50% no further neurological
      deterioration was observed. Imaging revealed for 88% of the patients a reduced
      uptake of contrast medium or a regression of the tumor size. Six patients with
      acoustic neurinoma had anacusis already before radiotherapy. Regarding the other
      patients in the follow-up, hearing improved in 1 patient, 1 patient showed
      hearing deterioration, and all other patients hearing remained constant. MR and
      CT imaging revealed in 10 patients with acoustic neurinoma a reduced uptake of
      contrast medium and in 1 patient a tumor diminution. From the patients with
      arteriovenous malformation only 4 have been followed for more than 2 years after
      treatment. Therefore, statements about the rate of obliteration are not possible
      yet. Concerning pretherapeutic symptoms (headache 22%, convulsion 28%,
      neurological deficits 11%) 8/17 (47%) of the arteriovenous malformation patients
      showed an improvement, in 8 patients clinical findings were unchanged and 1
      patient showed neurological deterioration. CONCLUSION: The stereotactic system
      SRS 200 allows an excellent mechanical accuracy in the radiosurgery with linear
      accelerators.

PMID- 8571194
TI  - Effects of differing rates of protamine reversal of heparin anticoagulation.
AB  - BACKGROUND: Protamine sulfate reversal of heparin anticoagulation may be
      associated with adverse cardiovascular side effects. The purpose of this study
      was to determine whether diminished systemic oxygen consumption and hemodynamic
      changes were more likely to accompany rapid versus slow protamine administration.
      METHODS: Fifteen patients undergoing abdominal aortic aneurysm resection in a
      prospective randomized double-blinded study received intravenous protamine (1.5
      mg/kg) rapidly during a 3-minute period (group I, n = 7) or slowly during a 15
      minute period (group II, n = 8). Systemic oxygen consumption (VO2) and
      hemodynamic parameters were assessed for up to 20 minutes after protamine
      administration began. RESULTS: Blood pressure declines (millimeters of mercury)
      were greatest in group I with rapid protamine administration (-19 systolic and -9
      diastolic) compared with group II with slow protamine administration (-12
      systolic and -1 diastolic). Heart rate fell markedly in both groups I and II.
      Cardiac output (CO) declined in group I at virtually all time periods. Similar CO
      declines in group II occurred 10 minutes after protamine infusion had begun and
      persisted for 3 minutes after protamine administration was complete. Maximum VO2
      decreases were -16% (60 seconds into protamine infusion) and -13% (1.5 minutes
      after protamine infusion) in groups I and II, respectively, with statistically
      significant declines (p < 0.05) occurring only in group I compared with baseline
      values. Statistically significant differences (p < 0.01), however, were found
      when mean declines during and after protamine infusion were compared with
      controls for both CO and VO2 in both groups. CONCLUSIONS: Significant declines in
      systemic VO2 and hemodynamic perturbations accompany protamine reversal of
      heparin anticoagulation during aortic surgery. Rapid protamine administration
      increases the magnitude of these adverse responses.

PMID- 8571195
TI  - Relevance of bacterial cultures of abdominal aortic aneurysm contents.
AB  - BACKGROUND: To establish further insight into the relevance of intraoperative
      bacterial cultures of abdominal aortic aneurysm contents a study was performed of
      the rate of occurrence of prosthetic graft infection after aneurysm repair.
      METHODS: Bacterial cultures were obtained from 216 patients, who were followed up
      for more than 3.5 years after operation and studied retrospectively in a single
      center analysis. RESULTS: Thrombus cultures yielded bacteria in 55 of 216 (25.5%)
      cases, including 11 of 44 (25%) cases with ruptured aneurysms. Prosthetic
      infections (4 of 216; 1.9%) occurred more frequently (p < 0.02) in patients with
      positive thrombus cultures (3 of 55; 5.5%) than in patients with negative
      cultures (1 of 161; 0.6%). In two patients the species isolated from the thrombus
      was also cultured from the vascular prosthesis, although in one graft infection
      other organisms were also isolated. CONCLUSIONS: The presence of bacteria in the
      intraluminal thrombus does not appear to be an important factor in the
      development of graft infection after primary elective and urgent abdominal aortic
      aneurysm repair. Therefore routine intraoperative cultures are unnecessary unless
      clinical signs of infective aortitis are present.

PMID- 8571196
TI  - Obturator hernia: current diagnosis and treatment.
AB  - BACKGROUND: Obturator hernia is a rare pelvic hernia for which both diagnosis and
      therapy are difficult. Because symptoms are nonspecific and specific physical
      findings are often obscure, diagnosis of obturator hernia is often delayed until
      laparotomy for bowel obstruction. Strangulation is frequent, and mortality
      remains high (25%). Primary closure of the hernia defect is difficult because
      adjacent tissues are not easily mobilized. Although a variety of techniques have
      been described, surgical repair has not been standardized. METHODS: We report a
      case of bilateral obturator hernia with incarceration in association with
      bilateral femoral hernia in which these problems were satisfactorily addressed.
      RESULTS: The hernias were diagnosed by computed tomography (CT) scan and repaired
      with synthetic mesh placed in the preperioneal space. This technique is well
      suited to unilateral and bilateral combinations of obturator, inguinal, and
      femoral hernias. CT scan in the work-up of severe gastrointestinal symptoms with
      weight loss may lead to a diagnosis of occult hernia, thereby allowing elective
      repair and, hopefully, a reduction in mortality risk. CONCLUSIONS: We recommend
      CT scan for suspected obturator hernia and preperitoneal mesh repair of
      noninfected cases.

PMID- 8571197
TI  - Obturator hernia: the usefulness of computed tomography in diagnosis.
AB  - BACKGROUND: Delay in diagnosis and treatment of the rare obturator hernia often
      leads to high resection and mortality rates. Reviews of the clinical courses and
      the reliability of computed tomography (CT) in early diagnosis are reported.
      METHODS: Seventeen patients with obturator hernias were treated between April
      1983 and December 1994. Except for one man, all were emaciated women who had
      undergone an average of 4.7 live deliveries. The mean age was 79.9 years.
      RESULTS: All patients had small bowel obstruction symptoms. Howship-Romberg sign
      was present in 11 patients. Twelve cases were correctly diagnosed before
      operation. After the introduction of CT in the diagnosis of suspected hernia
      cases, preoperative diagnosis was made on 9 of the 10 patients (90%) and CT was
      performed on 8 patients with 100% accuracy. CONCLUSIONS: Definite and early
      diagnosis is possible with the awareness of the clinical courses of this hernia
      and by performing CT on suspected cases.

PMID- 8571198
TI  - Evaluation of a novel synthetic material for closure of large abdominal wall
      defects.
AB  - BACKGROUND: This study was undertaken to compare the efficacy of a novel
      synthetic material (TMS-1) with polytetrafluoroethylene, polypropylene, and
      primary closure of experimentally fashioned clean and contaminated abdominal
      wounds. METHODS: One square centimeter full-thickness abdominal wall defects were
      created in each of the four abdominal quadrants of anesthetized rats (n = 6).
      Patches of polytetrafluoroethylene, polypropylene, and a polyurethane
      polypropylene composite material (TMS-1) were used to repair three of these
      defects; the fourth was primarily closed. A second group of rats (n = 9)
      underwent the same operative protocol; however, peritonitis was induced at the
      time of operation by using the fecal inoculation technique. Animals were killed 2
      to 3 weeks later, and surface area and severity of formed adhesions were
      assessed. RESULTS: By all methods of assessment, primary closure proved
      significantly superior to all other methods of closure in clean and contaminated
      conditions. The three synthetic materials were equally matched for surface area
      involved in adhesion formation. When compared with the other synthetic materials,
      TMS-1 was associated with significantly milder adhesions in uninfected (p <
      0.002) and in infected (p < 0.002) conditions. CONCLUSIONS: The clear superiority
      of TMS-1 over other nonabsorbable synthetic materials shown in this pilot study
      warrants further investigation relative to its use to close large abdominal wall
      defects.

PMID- 8571199
TI  - Penetrating injuries of the iliac arteries: a South African experience.
AB  - BACKGROUND: We did a retrospective study of 62 patients with penetrating injuries
      of the iliac arteries. METHODS: The cause of injury was gunshot wound in 85.5%
      and stabbing in 14.5%. The arterial repair was achieved by various means: lateral
      arteriorrhaphy, end-to-end anastomosis, and polytetrafluoroethylene interposition
      grafts. RESULTS: There was a 42% mortality rate from exsanguination or secondary
      coagulopathy directly related to the arterial injury. Persistent shock,
      resuscitative thoracotomy, free intraperitoneal hemorrhage, and the number of
      vascular injuries were directly related to mortality. CONCLUSIONS: A high index
      of suspicion, aggressive resuscitation, and prompt surgery are necessary to
      improve the chances of surviving this ominous injury.

PMID- 8571200
TI  - Hepatic hypoperfusion after intestinal reperfusion.
AB  - BACKGROUND: Intestinal ischemia-reperfusion injury (IIR) induces hepatic and
      pulmonary dysfunction and thus has been used as a model of multiple organ failure
      syndrome. This study examines the hypothesis that hepatic blood flow is markedly
      reduced in this injury model. METHODS: Sprague-Dawley rats underwent 120 minutes
      of intestinal ischemia and 60 minutes of reperfusion (IIR). Hepatic blood flow
      was measured with radiolabeled microspheres and Doppler flow probes. Hepatic
      dysfunction was quantitated by measuring bile flow and serum alanine
      aminotransferase and hepatic tissue adenosine triphosphate levels. Sham-operated
      animals served as controls. RESULTS: Intestinal ischemia reduced portal flow by
      66% when compared with sham-operated animals (p = 0.0001) but had no effect on
      hepatic arterial flow. In contrast, reperfusion reduced hepatic artery flow by
      80% when compared with controls (p = 0.002) with most of this change occurring
      within 5 minutes of reperfusion. IIR induced a 63% reduction in bile flow (p <
      0.05), a fivefold rise in serum alanine aminotransferase level (p < 0.0002), and
      a 33% reduction in hepatic adenosine triphosphate level (p < 0.05). CONCLUSIONS:
      These data suggest that IIR induces profound hepatic hypoperfusion, which is
      temporally related to acute hepatic dysfunction. This observation suggests that
      hepatic ischemia may contribute to IIR-induced liver injury.

PMID- 8571201
TI  - The Italian Registry for Adrenal Cortical Carcinoma: analysis of a
      multiinstitutional series of 129 patients. The ACC Italian Registry Study Group.
AB  - BACKGROUND: Adrenal cortical carcinoma is an uncommon tumor with a poor
      prognosis. The low incidence of this tumor makes it difficult to achieve reliable
      data on clinical manifestations, natural history, and the impact of therapies.
      The purpose of this study was to evaluate such aspects in a large series.
      METHODS: A retrospective series of 129 cases (55 men and 74 women, mean age of 49
      years) was collected from 18 surgical institutions. At the time of diagnosis
      45.7% of patients had endocrine symptoms. One hundred twenty-four patients
      underwent surgery, which was considered curative in 91 cases and palliative in
      33. Sixty-three patients had local disease, 48 had regional disease, and 43 had
      distant metastases. RESULTS: This study confirmed a higher incidence in the 40-
      to 50-year-old population with a female prevalence; hormonal hyperincretion was
      more common in women, but it was not caused by advanced disease. The overall 5
      year survival rate was 35%. Tumor stage and curative resection affected prognosis
      significantly. The influence of gender, side, age, and hormonal function has not
      been confirmed. Adjuvant therapies were ineffective in prolonging survival.
      Reoperated patients experienced better survival (mean, 41.5 months) than
      nonreoperated cases (mean, 15.6 months). CONCLUSIONS: The poor prognosis of
      adrenal cortical carcinoma may be improved by early diagnosis and complete
      resection. Radical surgery is the sole effective therapy, particularly in early
      stages. Surgical treatment of recurrence seems to improve survival and should be
      attempted systematically. Adjuvant therapies obtained contrasting results, and
      their role should be evaluated in prospective multicentric trials.

PMID- 8571202
TI  - Smooth muscle tumors of the gastrointestinal tract: analysis of prognostic
      factors.
AB  - BACKGROUND: The survival rates and therapeutic approaches to gastrointestinal
      leiomyoma and leiomyosarcoma vary widely. This review analyzes the clinical
      symptoms and signs, the results of the pathologic examination, and the DNA makeup
      of these tumors and determines the factors that affect the prognosis of patients
      who have leiomyosarcoma. METHODS: Flow cytometric DNA analysis was performed in
      80 patients with gastrointestinal smooth muscle tumors to establish the
      correlation of DNA ploidy with tumor size and stage and histologic grade. Using
      univariate and multivariate analyses, we investigated tumor size, histologic
      grade, association with gastrointestinal bleeding, DNA makeup, operative
      procedure, age, gender, and tumor necrosis as they affect the long-term survival
      of 45 patients with leiomyosarcoma. The Kaplan-Meier method was used to determine
      the survival rates and the log-rank method was used to compare survival rates
      between the two groups. RESULTS: Between 1986 and 1992, operations were performed
      on the 80 gastrointestinal smooth muscle tumors--esophageal 1, stomach 32,
      intestinal 33, colonic 2, and rectal 12. The most common symptoms and signs were
      gastrointestinal bleeding (43.8%), abdominal mass (37.5%), and abdominal pain
      (21.3%), and the tumors were classified as leiomyoma 35, low-grade leiomyosarcoma
      24, and high-grade leiomyosarcoma 21, according to the cellular atypia and
      mitotic rate. DNA ploidy correlated with histology grade (r = 0.70, p < 0.01) and
      tumor size (r = 0.31, p < 0.01) but not with localized or advanced tumors. Only
      one patient with leiomyoma died of liver metastasis during the follow-up period.
      In univariate analysis of the 45 patients with leiomyosarcoma, the survival rate
      was poor in men with tumor sizes greater than 5 cm, incomplete resections,
      advanced tumors, and high-grade tumors. With multivariate Cox regression analysis
      only advanced tumors (p < 0.01) and high-grade tumors (p < 0.01) were the
      independent factors that affected survival. CONCLUSIONS: Leiomyosarcomas usually
      measure more than 10 cm. In univariate analysis the significant factors affecting
      the survival rate of patients with leiomyosarcoma are maleness, size greater than
      5 cm, inadequate resection, and advanced-stage and high-grade disease. In
      multivariate Cox regression analysis advanced-stage and high-grade leiomyosarcoma
      are the only independent factors affecting survival. DNA ploidy correlates with
      the size and the grade of gastrointestinal smooth muscle tumors but not with
      tumor stage. DNA ploidy does not affect independently the survival of
      leiomyosarcoma.

PMID- 8571203
TI  - Granulocyte-macrophage colony-stimulating factor inhibits tumor growth during the
      postoperative period.
AB  - BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) may have
      important antineoplastic properties because it induces macrophage tumoricidal
      activity in vitro. We examined the inhibitory effect of GM-CSF on tumor growth in
      a murine carcinoma model and whether this inhibitory effect would persist during
      the postoperative period. Potential macrophage-mediated mechanisms were studied.
      METHODS: The effect of GM-CSF on macrophage function in vitro was assessed by
      measuring superoxide anion and interleukin-6 production, percentage phagocytosis
      of Candida albicans, and percentage Ia expression. GM-CSF's effect on tumor
      volume was assessed first in a murine tumor model and second to examine whether
      these effects also occurred during the postoperative period in the same model
      after laparotomy. Macrophage function in the latter study was assessed by
      measuring superoxide anion, cytotoxicity, and tumor necrosis factor production.
      RESULTS: GM-CSF treatment was associated with a decrease in tumor volume on day 4
      after the initiation of GM-CSF treatment (0.93 +/- 0.08 cm3 for control versus
      0.34 +/- 0.08 cm3 for GM-CSF; p < 0.05). This effect was also seen after
      laparotomy (1.07 +/- 0.2 cm3 for laparotomy+saline versus 0.16 +/- 0.04 cm3 for
      laparotomy+GM-CSF, p < 0.05). In vivo macrophage function showed increased
      superoxide anion, cytotoxicity, and tumor necrosis factor-alpha production from
      macrophages obtained from GM-CSF treated animals compared with saline treated
      controls. CONCLUSIONS: Tumor growth is inhibited by GM-CSF treatment, and this
      effect also occurs after laparotomy. Thus, GM-CSF may have a therapeutic role in
      the treatment of the tumor bearing host after operation.

PMID- 8571204
TI  - Kinetics of neurotensin gene expression in the developing gut.
AB  - BACKGROUND: Expression of the gene encoding neurotensin (NT/N) is regulated in a
      strict temporal- and spatial-specific pattern during gut development; the
      mechanisms (that is, transcriptional versus posttranscriptional) responsible for
      this expression pattern are not known. The purpose of this study was to determine
      whether developmental changes in NT/N expression reflect alternations in gene
      transcription. METHODS: Sensitive ribonuclease protection assays were performed
      with a rat NT/N genomic probe containing the entire sequence of both exon 1 and
      intron 1 hybridized with RNA from fetal (day 19) and postnatal (days 14, 28, and
      60) rat jejunum and ileum; signals were quantitated densitometrically. RESULTS:
      Mature (exon 1) and precursor (exon 1 + intron 1) NT/N RNA, initially low in the
      fetus, increased dramatically by postnatal day 14 and attained maximal levels by
      day 28. NT/N RNA levels remained stable in the ileum of the 60-day-old rat but
      decreased in the jejunum, consistent with the typical expression pattern in the
      gut. CONCLUSIONS: Concomitant changes in expression of precursor and mature NT/N
      RNA suggest that NT/N gene regulation occurs at the level of transcription in the
      gut during development. Identifying the factors that regulate NT/N gene
      transcription is crucial to our understanding of how neurotensin functions in the
      gut.

PMID- 8571205
TI  - Alterations in DNA proliferation in gastric stump mucosa with special reference
      to topography.
AB  - BACKGROUND: Gastric stump carcinoma occurs more frequently at the anastomotic
      site than at other areas of the gastric remnant. This study was conducted to
      determine whether alterations in cell dynamics could be detected in the normal
      looking gastric remnant mucosa and to ascertain any difference in cell dynamics
      between the anastomotic site and other area. METHODS: Sixty-three patients who
      underwent curative subtotal gastrectomy for gastric adenocarcinoma were examined
      8 to 130 months after operation. Mucosa at the anastomotic site and at the
      greater curvature were endoscopically biopsied. Cell dynamic changes were
      examined by flow cytometry, bromodeoxyuridine in vitro labeling, and oncogene (K
      ras and c-myc) amplification and translocation by Southern blot analyses.
      RESULTS: Inflammatory changes were observed in more than 60% of the cases both at
      the anastomotic site and at the greater curvature both macroscopically  and
      microscopically. Blood flow, measured by laser Doppler flowmeter, was
      significantly decreased at the anastomotic site compared with the greater
      curvature (25.0 +/- 8.1 and 32.2 +/- 9.4 mg/min/100 mg tissue, respectively; p <
      0.05). Analysis of DNA histograms obtained by flow cytometry revealed a small
      peak at the right shoulder of 2N peak in 33% of the specimens obtained from the
      anastomosis site and in 15% of those from the greater curvature (p < 0.05). The
      number of cells at S phase measured by bromodeoxyuridine in vitro labeling was
      also significantly greater at the anastomotic site than at the greater curvature.
      None of the five patients with aneuploid DNA histograms at the anastomotic site
      had detectable amplification or translocation of K-ras or c-myc gene in mucosal
      tissue. CONCLUSIONS: More marked changes in the mucosal cell dynamics observed at
      the anastomotic site may partially explain the higher incidence of gastric stump
      carcinoma at the anastomotic site.

PMID- 8571206
TI  - Perioperative respiratory management with fiberoptic bronchoscopy in pediatric
      living-related liver transplantation.
AB  - BACKGROUND: Perioperative respiratory complications have been one of the largest
      obstacles to pediatric management of pediatric liver METHODS: The roles of
      fiberoptic bronchoscopy in perioperative respiratory management of pediatric
      liver transplantation were studied retrospectively. RESULTS: In a group of 162
      children who underwent pediatric living-related liver transplantation, 44
      underwent 222 bronchoscopic procedures for diagnostic and therapeutic purposes
      during the perioperative period. Major indications for bronchoscopy were
      atelectasis/retention of airway secretion (n = 27), pneumonia (n = 19), pulmonary
      edema (n = 8), airway stenosis (n = 7), and airway bleeding (n = 6).
      Visualization of the airway was helpful in diagnosing respiratory complications;
      in seven infants, bronchoscopy revealed tracheobronchial stenosis that other
      diagnostic modalities failed to detect. In 16 of 19 patients with pneumonia,
      specimens taken by bronchoscopy were positive for specific pathogens.
      Bronchoscopy also proved to have significant therapeutic value, especially in
      airway cleaning; bronchial suctioning resulted in immediate reexpansion of the
      collapsed lung in 16 of 20 cases of atelectasis. No complications were noted
      other than severe hypoxia and bradycardia in one infant. CONCLUSIONS: Fiberoptic
      bronchoscopy is a safe and useful modality for perioperative respiratory
      management in pediatric liver transplantation.

PMID- 8571207
TI  - Innervated liver plays an inhibitory role in regulation of food intake.
AB  - BACKGROUND: With the onset of eating, the associated rise of dopamine in the
      lateral hypothalamus (LHA-DA) is thought to regulate quantity of food consumed
      per meal. Early release of LHA-DA induced by eating is facilitated by oronasal
      stimulation; we propose that the subsequent LHA-DA response induced by nutrients
      in the portal vein is dampened by the innervated liver. This was tested by
      measuring LHA-DA in normal rats: during parenteral feeding to bypass oronasal
      stimulation, while eating during parenteral feeding, and while eating only.
      METHODS: Rats had either total liver denervation or sham operation, with
      placement of a jugular vein catheter and LHA-DA microdialysis cannula. After a 3
      week recovery period total liver denervated rats were randomized to parenterally
      fed, food only, and parenteral plus food groups each with sham-operated controls
      in which LHA-DA was measured. RESULTS: No difference in LHA-DA release in food
      only groups occurred between total liver denervated or sham-operated rats. A
      significantly higher rise in LHA-DA was observed in total liver denervated versus
      sham-operated rats in parenterally fed (129% +/- 4% versus 116% +/- 2%; p < 0.05)
      and parenteral plus food (151% +/- 4% versus 134% +/- 4%; p < 0.05) groups.
      CONCLUSIONS: In total liver denervation versus sham operation, an increase in LHA
      DA release occurs during parenteral feeding and eating during parenteral feeding,
      suggesting that innervated liver inhibits LHA-DA release.

PMID- 8571208
TI  - Intracerebroventricular secretin enhances pancreatic volume and bicarbonate
      response in rats.
AB  - BACKGROUND: Although secretin has been found within the brain, its central role
      in pancreatic exocrine function has not been previously addressed. The hypothesis
      that intracerebroventricular secretin enhances pancreatic volume and bicarbonate
      output at doses that have no effect when given intravenously was tested. METHODS:
      Sprague-Dawley rats had a cannula stereotactically placed into the left lateral
      cerebral ventricle 24 hours before study. At laparotomy the bile and pancreatic
      ducts were separately cannulated and excluded for tared collections and
      bicarbonate assay. RESULTS: Increasing doses of intracerebroventricular secretin
      (0.005, 0.05, and 0.5 microgram/1.0 microliter) induced a significant dose
      related increase in bicarbonate output (2.95, 3.32, and 4.02 microEq/30 min,
      respectively) above basal (2.62 microEq/30 min) compared with control or
      intracerebroventricular saline treated animals. Pancreatic volume increased to
      59.7 microliters at the lowest intracerebroventricular dose and increased (p <
      0.025) to 65.8 microliters at the 0.05 intracerebroventricular secretin dose when
      compared with basal (59.4 microliters). To show that this was not a systemic
      effect of secretin, intravenous infusion of secretin at 0.005 and 0.05
      microgram/kg/hr failed to stimulate either volume or bicarbonate output compared
      with that observed with intracerebroventricular secretin over the same dose
      range. CONCLUSIONS: These observations indicate that intracerebroventricular
      secretin stimulates pancreatic volume and bicarbonate output and suggest that
      central secretin may play a role in the regulation of exocrine pancreatic
      secretion.

PMID- 8571209
TI  - Comparison of a modified Sugiura procedure with portal systemic shunt for
      prevention of recurrent variceal bleeding in cirrhosis.
AB  - BACKGROUND: There is no agreement on the management of patients with cirrhosis
      and recurrent variceal bleeding after failure of medical or endoscopic treatments
      or both. Portal systemic shunts are highly effective in preventing rebleeding but
      are associated with a high incidence of chronic encephalopathy. This study
      compared the results of a slightly modified Sugiura procedure (esophageal
      transection plus esophagogastric devascularization plus splenectomy) with those
      of nonselective portal systemic shunts in patients with previous variceal
      bleeding. METHODS: Fifty-four patients were included in this randomized
      controlled study between January 1984 and April 1989. The major end point was
      chronic encephalopathy. Secondary end points were recurrent variceal bleeding,
      survival, ascites, and hepatocellular carcinoma. RESULTS: Twenty-seven patients
      were assigned to each group. The rate of chronic encephalopathy was significantly
      (p = 0.002) lower after modified Sugiura procedure than after portal systemic
      shunt. Recurrent variceal bleeding was more frequent after modified Sugiura
      procedure than after portal systemic shunt, but the difference is not
      significant. One-, two-, and three-year survival rates were 93%, 81%, and 67%,
      respectively, in the modified Sugiura group and 78%, 66%, and 39%, respectively,
      in the portal systemic shunt group (p = 0.044). CONCLUSIONS: These results
      suggest that the modified Sugiura procedure is better overall than the
      nonselective portal systemic shunt in the management of patients with cirrhosis
      and recurrent variceal bleeding. Although the rebleeding rate is higher after the
      modified Sugiura procedure, this does not seem to affect mortality in these
      patients.

PMID- 8571210
TI  - Functional carotid body tumor: report of a case and a review of the literature.

PMID- 8571211
TI  - Uterine tumor in the heart: intravenous leiomyomatosis.

PMID- 8571212
TI  - Orthotopic kidney autotransplantation to facilitate repair of a recurrent
      pararenal aortic aneurysm.

PMID- 8571213
TI  - Congenital hepatoportal arteriovenous fistula.

PMID- 8571214
TI  - Hepatic arterioportal fistulas: surgical ligation of embolization?

PMID- 8571215
TI  - Effectiveness of extended lymphadenectomy in early gastric cancer.

PMID- 8571216
TI  - Pulsatile nature of growth hormone levels in critically ill trauma victims.

PMID- 8571217
TI  - Late pancreatic metastases from renal cell carcinoma.

PMID- 8571218
TI  - Body surface adaptations to boundary-layer dynamics.
AB  - Evolutionary processes have adapted nektonic animals to interact efficiently with
      the water that surrounds them. Not all these adaptations serve the same purpose.
      This paper concentrates on reduction of drag due to friction in the boundary
      layer close to the body surface. Mucus, compliant skins, scales, riblets and
      roughness may influence the flow velocity gradient, the type of flow and the
      thickness of the boundary layer around animals, and may seriously affect their
      drag in a positive or negative way. The long-chain polymers found in mucus
      decrease the pressure gradient and considerably reduced drag due to friction. The
      effect is probably due to channelling of the flow particles in the direction of
      the main flow, resulting in a reduction of turbulence. Compliant surfaces could
      probably reduce drag by equalising and distributing pressure pulses. However, the
      existing evidence that drag reduction actually occurs is not convincing. There is
      no indication that instantaneous heating, reducing the viscosity in the boundary
      layer, is used by animals as a drag-reducing technique. Small longitudinal ridges
      on rows of scales on fish can reduce shear stress in the boundary by a maximum of
      10% compared with the shear stress of a smooth surface. The mechanism is based on
      the impedance of cross flow under well-defined conditions. The effect has been
      visualized with the use of particle image velocimetry techniques. The function of
      the swords and spears of several fast, pelagic, predatory fish species is still
      enigmatic. The surface structure of the sword of a swordfish is shown to be both
      rough and porous. The height of the roughness elements on the tip of the sword is
      close to the critical value for the induction of a laminar-to-turbulent flow
      transition at moderate cruising speeds. A flow tank is described that is designed
      to visualize the effects of surface imperfections on flow in the boundary layer
      in direct comparison with a smooth flat wall. The flow in a 1 m long, 10 cm high
      and 1 cm wide channel is visualized by illuminating the particles in a thin laser
      light sheet. The first results show that a rough surface increases the shear
      stress in the boundary layer and makes it thinner. The function of the roughness
      on the sword of a swordfish is probably to reduce the total drag by generating
      premature turbulence and by boundary layer thinning, despite an increased
      friction over the surface of the sword. The function of the porous surface
      structures on the sword, and of the porous skins of sharks and of the castor oil
      fish, will probably be discovered soon using new particle image velocimetry
      techniques applied under strong magnification to visualize the local behaviour of
      the flow.

PMID- 8571219
TI  - Biological Fluid Dynamics. Proceedings of the SEB Symposium. Leeds, United
      Kingdom, 4-8 July 1994.

PMID- 8571220
TI  - Unsteady aerodynamics of insect flight.
AB  - Over the past decade, the importance of unsteady aerodynamic mechanisms for
      flapping insect flight has become widely recognised. Even at the fastest flight
      speeds, the old quasi-steady aerodynamic interpretation seems inadequate to
      explain the extra lift produced by the wings. Recent experiments on rigid model
      wings have confirmed the effectiveness of several postulated high-lift
      mechanisms. Delayed stall can produce extra lift for several chords of travel
      during the translational phases of the wingbeat. Lift can also be enhanced by
      circulation created during pronation and supination by rotational mechanisms: the
      fling/peel, the near fling/peel and isolated rotation. These studies have
      revealed large leading-edge vortices which contribute to the circulation around
      the wing, augmenting the lift. The mechanisms show distinctive patterns of vortex
      shedding from leading and trailing edges. The results of flow visualization
      experiments on tethered insects are reviewed in an attempt to identify the high
      lift mechanisms actually employed. The fling/peel mechanism is clearly used by
      some insects. The near fling/peel is the wing motion most commonly observed, but
      evidence for the production of high lift remains indirect. For many insects, lift
      on the upstroke probably results from delayed stall instead of the flex mechanism
      of isolated rotation. The large leading-edge vortices from experiments on rigid
      model wings are greatly reduced or missing around the real insect wings, often
      making the identification of aerodynamic mechanisms inconclusive. A substantial
      spanwise flow component has been detected over the aerodynamic upper wing
      surface, which should transport leading-edge vorticity towards the wingtip before
      it has much time to roll up. This spanwise transport, arising from centrifugal
      acceleration, is probably a general phenomenon for flapping insect flight. It
      should reduce and stabilise any leading-edge vortices that are present, which is
      essential for preventing stall and maintaining the circulation of high-lift
      mechanisms during translation.

PMID- 8571221
TI  - Dynamics of the vortex wakes of flying and swimming vertebrates.
AB  - The vortex wakes of flying and swimming animals provide evidence of the history
      of aero- and hydrodynamic force generation during the locomotor cycle. Vortex
      induced momentum flux in the wake is the reaction of forces the animal imposes on
      its environment, which must be in equilibrium with inertial and external forces.
      In flying birds and bats, the flapping wings generate lift both to provide thrust
      and to support the weight. Distinct wingbeat and wake movement patterns can be
      identified as gaits. In flow visualization experiments, only two wake patterns
      have been identified: a vortex ring gait with inactive upstroke, and a continuous
      vortex gait with active upstroke. These gaits may be modelled theoretically by
      free vortex and lifting line theory to predict mechanical energy consumption,
      aerodynamic forces and muscle activity. Longer-winged birds undergo a distinct
      gait change with speed, but shorter-winged species use the vortex ring gait at
      all speeds. In swimming fish, the situation is more complex: the wake vortices
      form a reversed von Karman vortex street, but little is known about the mechanism
      of generation of the wake, or about how it varies with speed and acceleration or
      with body form and swimming mode. An unresolved complicating factor is the
      interaction between the drag wake of the flapping fish body and the thrusting
      wake from the tail.

PMID- 8571222
TI  - Fluid flow through hair-bearing appendages: feeding, smelling and swimming at low
      and intermediate Reynolds numbers.
AB  - Many different types of animals use appendages bearing rows of hairs to capture
      food or molecules from the surrounding fluid, to locomote or to move fluids past
      themselves. The performance of these appendages, whose hairs operate at Reynolds
      numbers (Re) of 10(-5) to 10, depends on how much of the fluid that they
      encounter flows through the gaps between the hairs rather than around the
      perimeter of the whole array. We have employed mathematical modeling,
      microcinematography of hairy appendages on small aquatic animals and flow
      visualizations around dynamically scaled physical models to elucidate the factors
      that determine the leakiness of arrays of hairs. We found that rows of hairs
      operating at very low Re function as paddles, whereas those at Re near 1 operate
      like leaky sieves. The Re range through which the transition in leakiness occurs
      depends on the geometry of the appendage. We have discovered that different
      aspects of morphology and behavior are important in determining the leakiness of
      a hair-bearing appendage at different Re. Our study has revealed conditions under
      which morphological diversity of hairy appendages has little consequence for
      performance and other conditions under which simple changes in speed, size or
      mesh coarseness can lead to novel physical mechanisms of operation.

PMID- 8571223
TI  - Hydrodynamics of filter feeding.
AB  - A fluid mechanical model is developed for the filtering mechanism in mussels that
      enables estimates to be made of the pressure drop through the gill filaments due
      to (i) the latero-frontal filtering cilia, (ii) the lateral (pumping) cilia and
      through the non-ciliated zone at the ventral end of the filament. Calculations
      indicate that the lateral cilia can generate a sufficient pressure change to
      'pump' water through the gill filaments. The velocity profile across the
      filaments indicates that a backflow can occur in the centre of the channel.
      Normally the latero-frontal cilia would damp out this backflow but in the case
      when all the cilia are upright, two 'standing' eddies may form at the mouth of
      the channel, forcing the incoming water to the side.

PMID- 8571224
TI  - Insect sound production: transduction mechanisms and impedance matching.
AB  - The chain of sound production in insects can be summarised as: (1) muscle power-
      >(2) mechanical vibration of the sound-producing structure-->(3) acoustic loading
      of this source-->(4) sound radiation. At each link (-->) optimal impedance
      matching is desirable but, to meet other acoustic requirements, each stage has
      special properties. The properties of sound waves are discussed in the context of
      impedance matching between sources of different sizes or configurations and the
      surrounding fluid medium. Muscles produce high pressures over small areas, but
      sound sources produce low pressures over large areas. Link 1-->2 requires a
      change in the force: area ratio between the muscle and the sound source. Because
      the source size is necessarily small, sounds tend to be produced at a higher
      frequency than that of the driving muscle contraction, so link 1-->2 may involve
      a frequency multiplication mechanism. This can also be regarded as a mechanism of
      impedance matching between the aqueous muscle and the structure from which the
      insect produces sound. Stage 2 typically involves a resonant structure that
      determines the song frequency and is excited by link 1-->2. If link 2-->3
      provides good impedance matching, the mechanical resonance is likely to be
      damped, with loss of song purity. So it is desirable for the stage 2 resonance to
      be sustained by coherent excitation and for the acoustic loading (link 2-->3) to
      maintain the dominant frequency between stages 2 and 4. Examples where this
      occurs are cricket wings and cicadas. At stage 3, the source size or
      configuration should allow impedance matching between the sound source (3) and
      its load (4). A variety of acoustic devices are exploited, leading to loud,
      efficient sound production. Examples that use resonant loads, tuned to the
      insects' song frequency, are the burrows of mole crickets and the abdomens of
      cicadas. Overall, the mechanisms of sound production of many insects are capable
      of producing songs of high species-specificity that act as long-range signals.

PMID- 8571225
TI  - Swimming of dolphins: experiments and modelling.
AB  - A critical analysis of the numerous works on dolphin swimming shows that several
      uncertainties led to incorrect conclusions concerning the estimates of dolphin
      drag coefficients. Original results on dolphin kinematics and hydrodynamics
      indicate the existence of a drag-reduction mechanism, caused by the formation of
      a negative pressure gradient along the body during active swimming. The
      mathematical model for this mechanism is presented.

PMID- 8571226
TI  - High Reynolds number flow in tubes of complex geometry with application to wall
      shear stress in arteries.
AB  - The arterial systems of mammals contain many generations of branching, curved,
      elastic tubes, and the flow in them is unsteady. The flow details are important
      in determining the distribution of wall shear stress in arteries, a major factor
      in atherogenesis. The purpose of this paper is to point out that unsteady flow at
      realistic values of the Reynolds number (several hundred) and frequency parameter
      is much more complicated than a knowledge of steady flow in simpler geometries
      would suggest. Three-dimensional effects in curved, branched or indented tubes
      introduce secondary motions and horseshoe vortices, under which the wall shear
      can remain high for a considerable distance downstream. Unsteady flow in two
      dimensional, non-uniform tubes can lead to regions of flow separation far from
      the non-uniformity, again associated with high wall shear, not low shear as for
      two-dimensional, steady, separated flow. Moreover, both two- and three
      dimensional flows can be non-unique, so that the same driving pressures in the
      same geometry can lead to different flow patterns, depending on the initial
      conditions. There is great sensitivity to small geometric and temporal
      perturbations, making it very difficult to predict flow in one arterial
      bifurcation from a knowledge of another, or even at a particular site in one
      subject from a knowledge of another. Vessel elasticity is an additional
      complicating factor whose effects remain to be assessed in detail.

PMID- 8571227
TI  - Arterial Windkessels in marine mammals.
AB  - In marine mammals, the aortic arch is enlarged relative to the descending aorta
      to varying degrees in different species. The ratio of maximal diameter of the
      arch to that of the thoracic aorta is about 2.3 in the harbour seal (Phoca
      vitulina), 3.6 in the Weddell seal (Leptonychotes weddelli) and 3.2 in the fin
      whale (Balaenoptera physalus), compared with only 1.4 in the dog. This anatomical
      specialisation probably provides increased volume capacitance in the arterial
      circulation as an adaptation to diving bradycardia. Data on the morphometric and
      mechanical properties of aortic tissues from seals and fin whale are compared. In
      the harbour seal, more than 80% of the volume change in the entire thoracic aorta
      that results from a pressure pulse occurs in the bulbous arch, and this is more
      than 90% in the Weddell seal and fin whale. The enhanced capacitance of the arch
      in the harbour seal is primarily due to its larger diameter, as the relative wall
      thickness and elasticity of the arch and thoracic aorta are the same. A similar
      situation appears to exist in the larger Weddell seal, although extrapolation of
      the pressure-volume curves suggests that the arch might be somewhat less stiff
      than the thoracic aorta. In addition to being greatly expanded, the aortic arch
      of the fin whale is also much more distensible than the relatively thin-walled
      and much stiffer descending aorta. At the estimated mean blood pressure, the
      elastic modulus of this vessel is 12 MPa, or 30 times that of the aortic arch.
      The major haemodynamic consequence of this type of arterial modification is that
      the aortic arch acts as a Windkessel, i.e. the capacitance of the aorta is
      increased significantly close to the heart, leading to a reduced characteristic
      impedance and probably reduced pulsatility in the descending aorta. In the
      extreme case of the whale, the arterial capacitance is shifted entirely to the
      arch, and the impedance change at the entrance to the thoracic aorta is so high
      that this probably represents the major reflection site in the arterial tree.

PMID- 8571228
TI  - The dynamics of collapsible tubes.
AB  - The importance of collapsible-tube phenomena derives primarily from blood, air
      and urine flows in mammals, although similar principles underlie invertebrate
      jetting and the avian syrinx. Biological fluid conduits have flexible walls and
      many experience higher external than internal pressures during physiological
      manoeuvres. The tube typically becomes noncircular, and large shape and cross
      sectional area changes occur for small transmural pressure change. Two
      consequences ensue: a highly nonlinear constitutive relationship, and strong
      coupling between the fluid and solid mechanics. Depending on how flow is
      controlled, the tube can exhibit flow-rate-independent pressure-drop, or pressure
      drop-independent flow-rate, or a locally negative slope to the pressure-drop to
      flow-rate relationship. At sufficiently large Reynolds number, these behaviours
      are accompanied by self-excited oscillation in a surprising variety of modes,
      including aperiodic ones. Chaotic behaviour has been predicted numerically, but
      not unequivocally demonstrated. Intrinsic chaotic oscillation must be
      distinguished from sensitivity to turbulent through-flow. To this end, the
      response to periodic upstream forcing is currently being investigated.

PMID- 8571229
TI  - A general method for the computer simulation of biological systems interacting
      with fluids.
AB  - At this Symposium on Biological Fluid Dynamics, it is appropriate to ask whether
      there is any common theme that unites the diverse problems that arise in the
      study of living systems interacting with fluids. The answer that immediately
      comes to mind is this: biological fluid dynamics invariably involves the
      interaction of elastic flexible tissue with viscous incompressible fluid. (In
      many cases the tissue is not only elastic, it is also active, i.e. capable of
      doing work on the fluid). This paper describes the immersed boundary method,
      which is a general framework for the computer simulation of biofluid dynamic
      systems. This method has already been applied to blood flow in the heart
      (including the computer-assisted design of prosthetic cardiac valves), platelet
      aggregation during blood clotting, aquatic animal locomotion, wave propagation
      along the basilar membrane of the inner ear, and flow in collapsible tubes. In
      the immersed boundary method, the elastic (and possibly active) biological tissue
      is treated as a part of the fluid in which additional forces (derived from the
      tissue stresses) are applied. Because the tissue is represented in terms of its
      force field, the method remains straightforward, even when the geometry of the
      biological tissue is complicated, dynamic and not known in advance.

PMID- 8571230
TI  - Shear-augmented dispersion in the respiratory system.
AB  - Biological systems contain numerous examples of shear-augmented dispersion in
      which gradients in the velocity profile act in concert with lateral mixing or
      molecular diffusion to cause materials to disperse at an enhanced rate. Some of
      the better known examples are found in the respiratory or cardiovascular systems,
      but other applications include the dispersal of pollutants discharged into a
      flowing stream, the mixing of contaminants in groundwater flows and the
      possibility of enhanced transport rates through tissues subjected to transient
      loads. This review focuses on two examples in the respiratory system, bolus
      dispersion and high-frequency ventilation, that draw upon a broad range of
      fundamental studies in shear-augmented dispersion. Simple examples are considered
      which contain specific features of the considerably more complex real situations.
      These features include, for example, the effects of turbulence, secondary flows,
      absorption by the walls, aerosol deposition, complex geometries and oscillatory
      flow. A scaling analysis is presented that yields the approximate dependence of
      effective diffusivities associated with shear-augmented dispersion when more
      detailed analyses are either not warranted or too complex to be tractable.

PMID- 8571231
TI  - Pressure versus flow in biological pumps.
AB  - The pumps with which organisms move fluids span nearly a ten-million-fold
      pressure range. As in human technology, positive displacement pumps (osmotic,
      valve-and-chamber, peristaltic, etc.) are used for high-pressure applications and
      fluid dynamic pumps (using hydrofoils, cilia, aspirators, etc.) for low
      pressures. But while pressure capability or system resistance dichotomizes pumps
      by operative mechanism, the values of a dimensionless pressure-flow index prove
      more relevant to their biological roles; this index is a ratio of overall
      pressure drop in the system to pressure drop due to viscous resistance to flow.

PMID- 8571232
TI  - Mechanics of blood flow in the microcirculation.
AB  - The microcirculation in most tissues consists of an intricate network of very
      narrow tubes. In analyses of blood flow through the microcirculation, inertial
      effects can be neglected, but continuum models for blood cannot be assumed, since
      blood is a concentrated suspension of cells with dimensions comparable to vessel
      diameters. These cells strongly influence blood flow. About 45% of blood volume
      consists of red blood cells, whose key mechanical properties are known. A red
      cell has a fluid interior, surrounded by a flexible membrane, which strongly
      resists area changes, but bends and shears easily. White blood cells are
      comparable in size but much less numerous. They are less flexible than red cells
      and capable of active locomotion. Other suspended elements are much smaller than
      red cells: This review focuses on the mechanics of red cell motion in the
      microcirculation. Experimental and theoretical studies of blood flow in uniform
      tubes, bifurcations and networks are discussed. Comparisons between predicted and
      observed flows in networks imply that resistance to blood flow in living
      microvessels is higher than that in uniform tubes with corresponding diameters.
      Living microvessels have non-uniform geometries, and red cells must deform
      continually to traverse them. Theoretical results are presented implying that
      these transient deformations contribute to increased flow resistance in the
      microcirculation.

PMID- 8571233
TI  - Modelling the structural pathways for transcapillary exchange.
AB  - The ultrastructural pathways and mechanisms whereby endothelial cells and the
      clefts between the cells modulate capillary permeability to water and solutes
      have been a central unresolved question in microvessel transport since the early
      1950s. Freeze-fracture studies and ultrathin serial sections have demonstrated
      that endothelial cells are joined by an array of junctional strands which are
      interrupted at intervals, allowing for the passage of water and solutes, whereas
      cytochemical studies have indicated that the endothelial surface and portions of
      the wide part of the cleft contain matrix components. Neither constricted slit
      models based on the classic pore theory nor fiber matrix models are able to
      explain the large body of existing permeability measurements. In this review, we
      shall describe new three-dimensional modelling approaches which have resulted in
      a major revision of current ideas about the pathways for water and solutes
      through the junction strand and the structures that determine the molecular
      filter. For frog mesentery capillaries, these models predict (i) that the primary
      pathway for small ions is a previously unrecognized family of 2nm small pores
      that are distributed along the length of the junction strand; (ii) that the
      primary pathway for water and intermediate-sized solutes (1-3.5 nm radius) is an
      infrequent 150 nm long orifice-like pore whose height is the same as that of the
      wide part of the cleft; (iii) that the sieving structure for these solutes is a
      fiber layer, typically 100 nm thick, which extends from the surface into the
      entrance region of the cleft and (i.v.) that the interpretation of low molecular
      weight tracer studies to define the permeability pathways depends on the time
      dependent filling of the extravascular space.

PMID- 8571234
TI  - The role of the lateral line in active drag reduction by clupeoid fishes.
AB  - The lateral-line canals, confined in clupeoid fishes to the two sides of the
      head, are centred on the two lateral recesses, where thin membranes separate the
      sea water in the lateral-line system from another fluid (perilymph) in that
      subcerebral canal which passes through the head between the two lateral recesses.
      Any pressure difference between the recesses can accelerate fluid in the
      subcerebral canal, but it is only the effective acceleration of that fluid (i.e.
      relative to the lateral acceleration of the head) which can tend to generate
      motions--sensed by neuromasts--in lateral-line canals near the lateral recesses.
      Furthermore, it is the same effective lateral acceleration (relative to that of
      the head) that is experienced by water in the thin boundary layer on the surface
      of the head, where it tends to generate 'crossflows' that may act to increase
      hydrodynamic resistance (i.e. drag) to the fish's normal swimming movements.
      These regular swimming movements produce oscillatory sideslip of the fish's head
      which, by itself, would give such substantial values to the effective
      acceleration that lateral-line sensors near the lateral recesses would be
      saturated during normal swimming movements. Any such permanent state of
      saturation seems rather unlikely. An alternative hypothesis is that the fish
      actively produces an oscillatory turning of the head, controlled by the sensory
      output of those same neuromasts in such a way that this output is kept to a
      minimum. Then that effective pressure difference, which is responsible for the
      effective lateral acceleration both of perilymph in the subcerebral canal and of
      sea water in the boundary layer on the head, would be minimised--with
      advantageous drag-reduction consequences. In order to test this hypothesis, a
      detailed hydrodynamic analysis was carried out. It suggested that, in order to
      minimise the effective pressure difference, the yaw angle (in radians) of the
      fish's head would need to be kept in phase with the sideslip velocity, their
      magnitudes being in a ratio of about 0.87 U-1 (where U is the swimming speed).
      Experiments on a swimming clupeoid fish confirmed these conclusions, both about
      phases and about magnitudes. By contrast, a purely passive response of the head
      to oscillatory sideforce on the caudal fin would be expected to give the yaw
      angle a substantial lag behind sideslip, along with a ratio of magnitudes much
      smaller than 0.87 U-1. Thus, the experiments seems to support the hypothesis
      regarding active control of drag reduction.

PMID- 8571235
TI  - Interactions between muscle activation, body curvature and the water in the
      swimming lamprey.
AB  - The travelling wave of curvature which propels a fish forward arises from the
      interaction of the patterns of motoneurone activity generated by the spinal cord
      with the mechanical properties of (1) the muscle, (2) the skin, bone and
      connective tissues of the body, and (3) the water in which it is swimming.
      Furthermore, in the lamprey, a powerful feedback system has been demonstrated
      which allows local body curvature to influence the timing of the activity pattern
      generated by the spinal cord. The relative timing between activation and
      curvature are illustrated for both closed- and open-loop conditions, using data
      from intact swimming lampreys and from an in vitro preparation of lamprey spinal
      cord and notochord. The mechanical behaviour of a lamprey has been simulated with
      a mathematical model based on springs, dashpots, light rods, point masses and
      power units incorporating properties of lamprey muscle. Results are presented
      which illustrate the behaviour of a lamprey out of water. To anticipate the
      inclusion of the lamprey body model in the computation of the fluid dynamics, a
      hydrodynamical model has been developed in which the body motion and the forward
      swimming have been prescribed by mathematical functions. Results are presented to
      illustrate the hydrodynamic vortex structure as predicted by a two-dimensional,
      time-dependent numerical solution of the Navier-Stokes equations, including both
      viscous and inertial terms.

PMID- 8571236
TI  - Invertebrate swimming: integrating internal and external mechanics.
AB  - Challenges in understanding design for locomotion in any swimming animal revolve
      around the complex interactions between the mechanics of fluid motions around an
      animal and the mechanics of internal force production. The former is governed by
      force-velocity relationships that arise from fluid motion, whereas the latter is
      governed by force-velocity relationships of both active (e.g. muscle) and passive
      tissues. In reality, all such relationships must be satisfied simultaneously in
      any swimming creature. Towards this end, I combine traditional analyses of muscle
      contractility, soft tissue mechanics and hydrodynamic models to examine how
      organism morphology, muscle physiology and mode of propulsion interact to affect
      swimming performance. This combination involves a solution to a set of equations
      that describe the relevant internal and external mechanics. The solution has the
      unique benefit of providing predictions for both body and propulsor kinematics.
      Such predictions are examined for a variety swimming animals and are compared
      with existing kinematic data. Armed with such an approach, I re-examine
      traditional scaling arguments to show that classical approaches that neglect
      internal mechanics predict swimming performance relationships that may not be
      physiologically feasible.

PMID- 8571237
TI  - Paths and patterns: the biology and physics of swimming bacterial populations.
AB  - The velocity distribution of swimming micro-organisms depends on directional cues
      supplied by the environment. Directional swimming within a bounded space results
      in the accumulation of organisms near one or more surfaces. Gravity, gradients of
      chemical concentration and illumination affect the motile behaviour of individual
      swimmers. Concentrated populations of organisms scatter and absorb light or
      consume molecules, such as oxygen. When supply is one-sided, consumption creates
      gradients; the presence of the population alters the intensity and the symmetry
      of the environmental cues. Patterns of cues interact dynamically with patterns of
      the consumer population. In suspensions, spatial variations in the concentration
      of organisms are equivalent to variations of mean mass density of the fluid. When
      organisms accumulate in one region whilst moving away from another region, the
      force of gravity causes convection that translocates both organisms and dissolved
      substances. The geometry of the resulting concentration-convection patterns has
      features that are remarkably reproducible. Of interest for biology are (1) the
      long-range organisation achieved by organisms that do not communicate, and (2)
      that the entire system, consisting of fluid, cells, directional supply of
      consumables, boundaries and gravity, generates a dynamic that improves the
      organisms' habitat by enhancing transport and mixing. Velocity distributions of
      the bacterium Bacillus subtilis have been measured within the milieu of the
      spatially and temporally varying oxygen concentration which they themselves
      create. These distributions of swimming speed and direction are the fundamental
      ingredients required for a quantitative mathematical treatment of the patterns.
      The quantitative measurement of swimming behaviour also contributes to our
      understanding of aerotaxis of individual cells.

PMID- 8571238
TI  - [Control over the viral DNA level of patients with hepatitis B in the prognosis
      of its chronicity].
AB  - Viral DNA in the blood was measured by molecular hybridization in 210 patients
      with acute hepatitis B (HB) running mildly. It was established that the disease
      chronicity may be predicted by dynamic control of HBV DNA content. Relevant
      algorithm has been derived. Early detection of the chronicity threat was of great
      importance for early start of preventive etiotropic antiviral therapy.

PMID- 8571239
TI  - [The characteristics of the epidemic process in hepatitis B, C and D in
      hemodialysis units and the experience of the vaccinal prevention of HB viral
      infection in a delimited population].
AB  - Patients and medical staff of hemodialysis centers were screened for HBV, HCV and
      HDV markers. The incidence of mixed infection in patients reached 34.8%, while in
      medical personnel it was only 3.4%. There was an increasing rate of HBV markers
      in persons who have been immunized with ENGERIX-B vaccine according to standard
      schedules one month, one year and three years after the vaccination.
      Administration of Cuban vaccine using modified schedules is perspective for wide
      immunoprophylaxis in medical staff. Immunization policy for hemodialysis patients
      needs further perfection.

PMID- 8571240
TI  - [The clinical manifestations, diagnosis and treatment of diphtheria in adults].
AB  - Diphtheria morbidity among adult population of Moscow is growing. The tests of
      different modes and schemes of heterogeneous antidiphtheria serum administration
      have found out that the highest efficacy of serotherapy was achieved with a
      single intravenous dose. Another treatment of diphtheria is hemosorption. Widely
      used in present-day clinical practice hemosorbents provide adequate elimination
      of the toxin from plasma. The authors analyse the present situation in clinical
      symptoms, complications, lethality of diphtheria basing on the data provided by
      S. P. Botkin's Hospital.

PMID- 8571241
TI  - [Hemostatic disorders in severe forms of diphtheria and their correction with
      dicinon].
AB  - The presence of thrombohemorrhagic syndrome (THS) has been established in 28
      patients with toxic severe diphtheria of oropharynx. In view of the leading role
      of platelet affection in progression of hemorrhagic disorders in diphtheria,
      dicinon treatment may be beneficial. THS implications in unfavourable outcome of
      the disease and prognostic significance of critical thrombocytopenia are
      considered.

PMID- 8571242
TI  - [A case of an unusual course in measles].
AB  - An adult woman with catarrhal measles developed idiopathic ketosis. The
      contributing factors were: diet noncompliance (taking meat rich in fat),
      emotional stress and fatigue, acute infection (measles).

PMID- 8571243
TI  - [The clinical manifestations of HIV infection during seroconversion].
AB  - 21 seroconversion HIV-infected subjects have been examined. 16 of them presented
      with acute symptoms. The disease in the period of seroconversion manifested with
      fever, weakness, headache, pain in the throat, enlargement of peripheral lymph
      nodes, polymorphous eruption. Typical mononucleosis-like syndrome occurred in 3
      patients only. Half of the patients had subclinical disease, no eruption was
      seen. Because of clinical indications only 8 of 21 patients were examined for HIV
      infection. One-third of the patients in seroconversion had moderate
      thrombocytopenia, probably of autoimmune nature. Autoimmune disorder of the
      thyroid was registered in 1 patient. The diagnosis of acute HIV infection is not
      easy in view of rare occurrence of immunodeficiency typical for this infection.
      Candidiasis of the mucosa was seen in 37.5%, low levels of CD4-lymphocytes in
      66.7% of the cases.

PMID- 8571244
TI  - [Acute intestinal infections and chronic alcoholism].
AB  - 153 chronic alcoholics were given treatment against food poisoning. 55 of them
      developed withdrawal syndrome, 98 had alcoholic psychosis including 88 with
      delirium tremens. The acute intestinal infection in these alcoholics was managed
      with rehydration using polyionic crystalloid solutions under controlled diuresis.
      Previous relief of central excitation contributed much to a positive treatment
      outcome.

PMID- 8571245
TI  - [The clinical, diagnostic and treatment characteristics of plague today].

PMID- 8571246
TI  - [Problems in the pathogenesis and pathogenetic therapy of hemorrhagic fever with
      renal syndrome].

PMID- 8571247
TI  - [A case of bronchial asthma complicated by mycosis].

PMID- 8571248
TI  - [Changes in the lipid composition of the blood serum lipoproteins during the
      hormonal treatment of patients with bronchial asthma].
AB  - Ultracentrifugation, thin-layer and gas-liquid chromatography were employed to
      study changes in lipid metabolism in 25 patients with bacterial asthma on
      glucocorticoid therapy. Before and 1 weeks after administration of glucocorticoid
      measurements were made of phospholipids, cholesterol and its esters,
      triacylglycerols in LDL, HDL2 and HDL3. It was found that hormone treatment leads
      to an increase in the total phospholipid pool in all lipoprotein fractions. High
      levels of lecithin and palmitinic acid contributed to improvement in composition
      of pulmonary surfactant. Decreased atherogenicity, a trend to membrane
      stabilization were positive, while high percentage of saturated fatty acids and
      low levels of polyenic acids in LDL and HDL2 were negative effects of hormone
      treatment. Correction of metabolism at the level of fatty acid composition is
      necessary.

PMID- 8571249
TI  - [The clinical and serological manifestations of Lyme disease in Russia].
AB  - Out of 86 Lyme's disease patients with a history of migrating erythema nervous
      system, cardiovascular and articular involvement was observed in 27, 6 and 43% of
      cases. Acrodermatitis was diagnosed in 2% of patients. Affection of locomotor
      system manifested with acute arthritis episodes or pains in major joints. 11
      patients of 12 examined at arthritis onset showed elevated titer of anti-Borrelia
      IgG antibodies. Serologically, of 80 patients with arthritis or arthralgia
      without prior migrating erythema 6 demonstrated antibodies to 5 and more Borrelia
      polypeptides.

PMID- 8571250
TI  - [Lyme arthritis: the joint lesions in Lyme borreliosis in the USA].
AB  - Of 55 untreated patients with erythema migrans only 20% were free of follow-up
      manifestations of Lyme's disease. The rest exhibited episodes of articular,
      periarticular or musculoskeletal pains (18%), one or more episodes of arthritis
      (51%) or chronic arthritis (11%). Lyme's arthritis arises due to invasion of
      Borrelia burgdorferi into articular tissues. This became evident after detection
      of borrelian DNA in the synovia. The study of different cytokine concentrations
      in the synovial fluid in 83 patients with Lyme's arthritis showed that chronicity
      of arthritis depends on IL-1b and IL-1ra balance. As indicated by examination of
      80 patients with Lyme's arthritis chronic persistence of articular syndrome in
      57% was associated with HLA-DR4, in 43% with HLA-DR2. Lyme's arthritis requires
      long-term treatment. In its failure arthroscopic synovectomy is indicated.

PMID- 8571251
TI  - [The clinical instrumental characteristics of the locomotor involvement in
      patients who have had Lyme disease].
AB  - Locomotor system has been studied in 24 patients with a history of Lyme's
      disease. All of them had arthralgia, 11 had relapsing arthritis, chronic
      arthritis occurred in 6 examinees. Arthritis presented as recurrent asymmetric
      mono-oligoarthritis affecting primarily joints of the lower limbs. Periarticular
      disorders were detected in 12 patients. Serologically, 18 of 24 patients had
      elevated titers of antibodies to Borrelia burgdorferi in indirect
      immunofluorescence test. Scintigraphy revealed polyarticular lesions in many
      cases, ultrasound investigation of the joints confirmed inflammatory nature of
      the pathological changes. It is inferred that combined methods of examination in
      diagnosis of Lyme's arthritis (titers to antibodies to Borrelia burgdorferi,
      ultrasound investigations, scintigraphy of the joints) provide most complete
      information.

PMID- 8571252
TI  - [The classification of Lyme borreliosis (Lyme disease)].
AB  - A new version of Lyme's disease classification based on the authors' experience
      and other classifications is proposed. It distinguishes periods of the disease
      (acute, subacute, chronic) and stages (I--isolated erythema migrans, II--local
      disseminated infection, III--generalized disseminated infection) as well as the
      signs which are significant in Lyme's disease diagnosis: erythematous and
      nonerythematous form, seropositivity or seronegativity against Borrelia
      burgdorferi. Subclinical (latent) infection, complications of Lyme's disease
      (fibromyalgia syndrome, chronic fatigue syndrome, etc.) and mixed-infection with
      tick-borne viral encephalitis are included as well.

PMID- 8571253
TI  - [The immunological diagnosis of chronic viral hepatitis].
AB  - Chronic viral diseases of the liver are associated with changes in immune
      reactions mediated by T and B lymphocytes and dependent in severity on
      etiological factor (virus of hepatitis B, delta, C, their combination), the
      disease stage (hepatitis, cirrhosis), the process activity, kind of immune
      correction. HBsAg, viral hepatitis B marker, was detected in 21.2% of 1400 cases
      with chronic active hepatitis and liver cirrhosis. 32% of HbsAg-seropositive
      patients had antibodies to delta-antigen. Antibodies to HBsAg, HCV were found in
      27.7 and 14.9% of the above patients. Chronic viral diseases of the liver with
      persistence of HBV, HDV and HCV markers are characterized by a complex of immune
      disorders, including a moderate rise in peripheral blood of IgM, IgG, IgA, IgE,
      Ig kappa, lambda, immune complexes, cryoglobulins, autoantibodies to subcellular
      structures as well as changes in regulatory (suppressor, helper) and effector
      (lymphokine-producing) functions of T lymphocytes, inhibition of phagocytosing
      capacity. The above shifts in immune status, clinical and biochemical activity of
      the disease are more pronounced in chronic active hepatitis with HCV markers
      compared to BHV. Of maximal intensity they were in combined viral infection
      HBV+HDV or HBV+HCV.

PMID- 8571254
TI  - [The basic syndromes of neurological disorders in Lyme borreliosis].
AB  - Long-term follow-up of 92 Lyme's borreliosis sufferers with different
      neurological syndromes allowed the authors to distinguish as the following basic
      nervous disturbances typical for this disease: peripheral neuropathies,
      encephalopathies, meningoencephalitis, serous meningitis. Peripheral neuropathies
      occurred most frequently (80%). The disease duration and severity were often
      substantial.

PMID- 8571255
TI  - [The humoral immunological response of patients with Lyme disease].
AB  - Indirect immunofluorescence (II), enzyme-labelled antibodies (ELA), immune
      blotting (IB) were used for serological evaluation of 74 patients with Lyme
      disease living in the North-West and Central regions of Russia. Both acute and
      chronic borreliosis can be seropositive or seronegative. As shown by II and ELA,
      these patients had a moderate humoral response, high titers of the specific
      antibodies being a rare finding. The range of anti-Borrelia antibodies (ABA)
      identified by IB is limited and, as a rule, includes antibodies to no more than 5
      proteins of Borrelia burgdorferi. The highest ABA levels were associated with
      locomotor lesions and were significantly greater of the above levels in patients
      with migrating erythema. Informative value of II and ELA in Lyme's disease
      diagnosis according to this study is equal because ELA is more sensitive, while
      II is more specific. They are both of little help in atypical borreliosis
      presentation. Most available of other adequate serological tests is IB.

PMID- 8571256
TI  - [Parvovirus B19 (PV-B19) and the human diseases it causes].
AB  - The author reviews the discovery of parvovirus B19, its characteristics,
      epidemiology, clinical and hematological features of acute and chronic forms of
      the infection in children and adults, diagnostic techniques, treatment of most
      severe forms.

PMID- 8571257
TI  - [Retroviruses in human infectious pathology].

PMID- 8571258
TI  - [A. I. Nesterov--an outstanding figure in Soviet medicine and public health].

PMID- 8571259
TI  - [The risk factors for unfavorable outcomes in rheumatism].
AB  - A prospective study was made of environmental factors effects on unfavorable
      cardial and cerebral outcomes of rheumatic fever (RF) assessed functionally,
      biochemically and psychologically. Some of RF predisposing factors (female sex,
      frequent nasopharyngeal infections, poor housing and occupational conditions)
      negatively affect outcomes of primary RF and contribute to emergence of valvular
      disease. The initial attack of activity I or III degree, pronounced carditis,
      active rheumatic process at discharge, recurrences, absence of year-round
      prophylaxis allow prognostication of valvular heart disease. The majority of the
      factors promoting valvular and circulatory disorders also contribute to the onset
      of psychic abnormalities, astheno-organic syndrome, in particular.

PMID- 8571261
TI  - [The interferon status and cellular immunity of pregnant women with viral
      hepatitis B].
AB  - The examination of 62 pregnant women with acute viral hepatitis B has established
      in them inhibition of interferon genesis and the presence of secondary T-cell
      immunodeficiency. The most pronounced and long-lasting was a fall of gamma
      interferon. A simultaneous lowering of alpha-, gamma- and serum interferon was
      indicative of complicated pregnancy or premorbid condition. A persistent
      deficient production of gamma-interferon and T lymphocytes, imbalance of their
      subpopulations promoted long-term course of hepatitis and persistence of HBsAg.

PMID- 8571260
TI  - [The diagnostic and prognostic significance of the indices of the immune response
      to streptococcal group A antigens in rheumatism].
AB  - Serum samples obtained from 33 patients with acute rheumatic fever (ARF), 60
      patients with rheumatic heart disease (RHD) and 30 adult healthy persons have
      been studied. Antibodies to streptococcal A polysaccharide (SAP) and lypoteichoic
      acid (LTA) were examined by ELISA, to streptolysin O by standard technique. SAP
      antibodies in high titers persisted from 5 to 12 months in ARF and rheumatic
      carditis patients especially when RHD was developing. High titers of antibodies
      to LTA and SLO persisted for 3 months since ARF onset, then fell (p < 0.05).
      ELISA proved sensitive in determination of antibodies to SAP and LTA. Its
      combination with determination of the titers to SLO antigens confirmed
      Streptococcus A infection involvement in emergence of ARF in all the cases
      including insidious or late-onset carditis and chorea. High levels of antibodies
      to SAP and LTA were more frequently detected in patients with RHD than in healthy
      persons (p < 0.001). Correlation between frequency of high levels of antibodies
      to SAP and bicillin 5 or erythromycin administration, duration of RHD was not
      established.

PMID- 8571262
TI  - [Polymyalgia rheumatica].
AB  - A case is reported of rheumatic polymyalgia rarely amenable to correct diagnosis.
      The response was achieved after glucocorticoid treatment. The diagnosis was based
      on the following criteria: age over 50, muscular pain (in two or more regions of
      the neck, shoulder and pelvic girdle, ESR above 35 mm/h, duration of the symptoms
      at least 2 months, limited movements in the cervical spine, shoulder and hip
      joints, weakness, subnormal appetite, fever, anemia, loss of weight.

PMID- 8571263
TI  - [The detection of secondary amyloidosis in rheumatoid arthritis by aspiration
      biopsy of the subcutaneous fatty tissue].
AB  - 81 rheumatoid arthritis patients were regularly and periodically examined in
      rheumatological department of Tartu University Clinic. Depending on the presence
      of amyloid in subcutaneous fat biopsies the patients were divided into two
      comparable groups: amyloid-positive (group 1 of 22 patients) and amyloid-negative
      (group 2 of 59 patients). Between the groups some differences were found: group 1
      patients had more active and severe course of rheumatoid arthritis and higher
      level of rheumatoid factor and circulating immune complexes in the sera. Before
      biopsy secondary amyloidosis was diagnosed in 17.4% of the examines, biopsy of
      abdominal subcutaneous fat increased this rate to 27.2%. We could not ascertain
      any effect of previous treatment on secondary amyloidosis development except the
      connection with long-term use of corticosteroids. The analysis of 10379 autopsies
      showed that cases of RA with amyloidosis account for 30.9% of all amyloidosis
      cases. Multiple stepwise regression analysis determined predisposition factors to
      secondary amyloidosis as severity of locomotor system involvement, long-term use
      of corticosteroids, high level of rheumatoid factor and activity of rheumatoid
      process.

PMID- 8571264
TI  - [The effect of basic therapy on the morphological picture of the rectal mucosa in
      patients with rheumatoid arthritis].
AB  - 140 rectal mucosa biopsies were obtained from 86 patients with rheumatoid
      arthritis (RA), from 54 RA patients prior to or after a year basic therapy with
      either methotrexate or sulfa drug (sulfasalazine or salazopyridazine). 80% of the
      examinees exhibited large macrophages, lymphoid follicules, IgM- and IgG
      containing cells. The knowledge of the initial morphologic changes in the rectal
      mucosa from RA patients helps predict efficacy of methotrexate or sulfonic drug
      treatment. Rectoromanoscopy with biopsy proved important diagnostic tool in RA
      capable of differentiating the disease variants, prompting valid therapeutic
      approach with control of the treatment results.

PMID- 8571265
TI  - [Jaccoud's arthropathy].
AB  - Jaccoud's arthropathy is a variant of deforming arthropathy affecting primarily
      hands. The author presents literature data and analysis of 28 original cases of
      valvular disease combined with chronic arthritis. Though these cases were
      diagnosed as Jaccoud's arthropathy, only one of them met Bywaters' criteria. This
      female patient is described. Jaccoud's arthropathy is suggested to arise due to
      connective tissue dysplasia resulting in soft tissue impairment in different
      rheumatic and nonrheumatic diseases. A working classification and additional
      criteria for postrheumatic Jaccoud's arthropathy are proposed.

PMID- 8571266
TI  - [The control of rheumatism in the 2nd half of the 20th century in Russia].

PMID- 8571267
TI  - The price of regulation. TMA study identifies costs of doing business.
AB  - Things used to be a lot simpler for Larry James, MD. An Austin allergist for
      almost 20 years, Dr. James used to be able to conduct lab tests on his patients
      in his office and have the results in as little as 20 minutes. Then along came
      the federal Clinical Laboratory Improvement Amendments (CLIA), passed by Congress
      in reaction to negative publicity (some critics called it media hysteria) over
      improperly read Pap smears, and Dr James' lab was out of business. Not because he
      did anything wrong, but because he was unwilling to put up with the bureaucratic
      hassle and expense of complying with CLIA.

PMID- 8571268
TI  - Better late than never. Stark I rules issued at last.
AB  - Keeping abreast of federal health-care laws and their accompanying rules is
      rarely easy. But compliance becomes especially difficult when one law is amended
      by a second law before rules clarifying the first law are even published. Such is
      the case with the Stark I and Stark II federal statutes.

PMID- 8571269
TI  - Cultural partnerships. Texas physicians team up with colleagues from the former
      Soviet Union.
AB  - Slowly but surely, the patients just stopped coming. Not because the hospital
      lacked beds or skilled doctors and nurses to take care of them, and not because
      they had anywhere else to go. They stopped coming, no matter how sick they got,
      because word got around that going to the hospital either didn't help or could
      make them sicker.

PMID- 8571270
TI  - Future of the federation. Can organized medicine keep pace with changing times?

PMID- 8571271
TI  - Order in the court. TEXPAC effort to reform state's highest court paying
      dividends.
AB  - "Clean slate in '88" was the rallying cry Texas physicians and a coalition of
      other business and professional groups used 8 years ago when they decided to take
      back the Texas Supreme Court. Frustrated by ongoing trial lawyer dominance of the
      court, the coalition led by the Texas Medical Association Political Action
      Committee (TEXPAC) launched an unprecedented grassroots campaign to put three new
      conservative justices on the nine-member court.

PMID- 8571272
TI  - Medical history. TMA 50-year club members helped make it.
AB  - They survived the Great Depression, won a world war, and touched millions of
      lives--from the downtrodden to heads of state--while helping to bring about the
      greatest advances in medicine the world has ever known. Now in retirement, the
      members of the Texas Medical Association's 50-Year Club look back and marvel at
      what they have witnessed.

PMID- 8571273
TI  - Why we need organized medicine.

PMID- 8571274
TI  - Physician work force in Texas: planning for the future.
AB  - A number of proposals have been advanced to solve the shortage of primary care
      physicians in the United States. We analyzed the supply of primary care and
      nonprimary care physicians in Texas and contrasted work force supply with
      projected need. Texas has a serious shortage of primary care physicians and an
      adequate supply of nonprimary care specialists only in major urban areas. We also
      analyzed attitudes of medical students in and graduates of The University of
      Texas medical schools to assess factors that influenced their career choices. The
      most influential factors were remarkably similar among all groups and were
      related primarily to personal attributes and experience. This study assesses the
      current physician work force in Texas and suggests means by which policy can be
      decided to affect the supply and distribution of physicians in Texas.

PMID- 8571275
TI  - Is obstetrics-gynecology a primary care specialty?
AB  - Suddenly everyone wants more primary care physicians. For several years, we
      collected data from senior medical students to relate their attitudes and beliefs
      about several clinical problems common to primary care to their choices of
      residencies. Because the Texas Medical Association's Special Committee on Primary
      Care included obstetrics-gynecology as a primary care specialty, we reviewed our
      data to see if the personal traits and professional role characteristics of
      seniors choosing obstetrics-gynecology differed materially from those of seniors
      choosing family medicine, internal medicine, or pediatrics. Results of this
      analysis put obstetrics-gynecology about as firmly in the primary care group as
      if the experimental design had planned it that way.

PMID- 8571276
TI  - Medical savings accounts will control health-care costs.

PMID- 8571277
TI  - [Use of databases in pharmacovigilance: two examples].
AB  - The association between asthma exacerbations and use of antiasthmatics has been
      studied with a drug dispensing database. Exacerbations were identified through
      use of oral corticosteroids and the risk was determined for each medication. use
      of fenoterol and oral xanthines increases the frequency of exacerbations, but a
      channelling phenomenon is not excluded. This method could be used in the study of
      treatment combinations or new treatments, facilitating the monitoring of
      asthmatic populations. A second study collects ambulatory drug use data (POM and
      OTC drugs) of elderly patients. These data are analysed for the distribution of
      several variables, such as concomitant use of several medications of the same
      therapeutic class. As an example, about 15 per cent of NSAIDs users also use
      aspirin, exposing themselves to increased risk for gastrointestinal effects.
      These studies illustrate the use of drug dispensing databases in monitoring
      populations at risk and assessing treatment quality.

PMID- 8571278
TI  - Antiarrhythmic drug-induced side effects: a prospective survey of 300 patients.
AB  - The purpose of this study was to define the characteristics and the frequency of
      antiarrhythmic drug-induced side effects. All patients referred for cardiological
      consultation and treated with antiarrhythmic drugs between April 1992 and October
      1993 were prospectively investigated. 300 patients were included in the study: 41
      (13.6 per cent) had drug-induced side effects, nine of which were serious: 5
      proarrhythmic effects, 1 pulmonary fibrosis, 1 peripheral neuropathy, and 2 acute
      cardiac failure. Side effects led to discontinuation of treatment in 26 cases
      (7.6 per cent). Statistical analysis showed that side effects occurred more
      commonly with disopyramide (46.1 per cent, P < 0.01) or propafenone (41.7 per
      cent, P < 0.05) and less frequently with sotalol (2 per cent, P < 0.01) than with
      the other drugs (flecainide 20 per cent; amiodarone 16.4 per cent; cibenzoline
      4.8 per cent; hydroquinidine 4.3 per cent). Side effects were more common on
      bitherapy (39 per cent) than on monotherapy (13 per cent) in general and in the
      amiodarone-treated group in particular. In conclusion, side effects of
      antiarrhythmic drugs involved 1/6 patients overall and led to discontinuation of
      treatment in 1/14. The frequency of proarrhythmias (1.1 per cent) was lower than
      previously reported, suggesting that recently published clinical trials have
      modified the prescription habits.

PMID- 8571279
TI  - [Evaluation of side effects of interferon-alpha in 72 patients treated for
      chronic active hepatitis C].
AB  - Interferon alfa (INF alpha), which is used in chronic active viral hepatitis,
      presents some safety problems. Side effects observed in 72 treated patients with
      chronic active hepatitis C are analysed in this retrospective study. Doses used
      were 3 or 9 M IU, three times a week, for 12 to 24 weeks. There were no contra
      indications to the treatment and all patients had the factors predictive of a
      satisfactory therapeutic response. Apart from general debility, there were side
      effects in 65 of the 72 patients as follows: flu-like syndrome (n = 39),
      gastrointestinal (n = 29), dermatological (n = 24), haematological (n = 23),
      neurological (n = 20), cardiovascular (n = 6) and thyroid (n = 6) disorders. For
      30 per cent of the patients, the dose was decreased (n = 6) or the treatment was
      withdrawn, temporarily (n = 5) or permanently (n = 10). These results are in
      accordance with those published and emphasize the need for clinico-biological
      monitoring during and after treatment. Indeed delayed thyroid disorders appear to
      be relatively common.

PMID- 8571280
TI  - [Movement disorders induced by drugs: experience at a pharmaco-vigilance center
      over five years].
AB  - The present retrospective study investigates the characteristics of drug-induced
      movement disorders notified to a Regional Drug Surveillance Centre. Among 4000
      general side effects spontaneously reported to the Centre between 1989 and 1993,
      122 were drug-induced movement disorders. Drug-induced parkinsonism (40 per cent)
      was mainly due to antidopaminergic agents (neuroleptics but also antiemetics or
      calcium channel blockers). Acute dyskinesia and dystonia (25 per cent) as well as
      tardive dyskinesia (14 per cent) involved mainly neuroleptics or antiemetics. Non
      parkinsonian tremors (11 per cent) were related mostly to tricyclic
      antidepressants. Involvement of other less often suspected drugs (non-imipramine
      antidepressants, cardiac or hypolipidaemic drugs, etc) is discussed.

PMID- 8571281
TI  - A 2-year evaluation of questions concerning "Drugs--Pregnancy" at the CRPV in
      Nantes March 1992--March 1994.
AB  - Since 1990, the 'Centre Regional de Pharmacovigilance' of Nantes has
      systematically monitored pregnant women exposed to drugs. To increase physicians'
      participation in this study (34 per cent), the protocol was modified in 1992.
      Phoned answers are confirmed by mail. At the supposed time of the delivery, the
      physician receives a questionnaire about the outcome of pregnancy. A second
      letter and phone call are planned. With this method, 89 per cent of the
      pregnancies were fully documented between March 92 and March 94. Answers are
      classified according to the type of the practice. Pregnancy outcome is studied
      according to the drugs and the moment of exposure during pregnancy. Quality of
      the information, motivation of the physicians, and the benefits and difficulties
      of this method are discussed.

PMID- 8571282
TI  - [Hypersensitivity to glucocorticoids: reflections on a published case report
      sample].
AB  - Hypersensitivity reactions associated with glucocorticoid treatment are rare but
      well known; the purpose of this study was to identify the responsible constituent
      (the excipient or the glucocorticoid). 32 cases published from 1970 have been
      analysed. In 75 per cent of cases, the patients received the glucocorticoid
      (hydrocortisone and methylprednisolone principally) by the intravenous route.
      Clinical manifestations reported were respiratory or cutaneous, with a short
      interval to onset. Skin tests were performed in 20 patients, but cutaneous
      challenge identified an agent responsible for hypersensitivity in only three
      cases. The heterogeneity of the test results in these 32 cases makes it difficult
      to identify a unifying explanation for the reactions, or propose a therapeutic
      schedule.

PMID- 8571283
TI  - [Neutropenia during treatment with fusidic acid: analysis of 5 cases].
AB  - Two cases of moderate neutropenia and 3 cases of severe neutropenia in the course
      of fusidic acid treatment for sepsis related to a hip prothesis or septic
      osteitis are reported. Neutropenia was always observed following routine blood
      cell count, after a mean of 21 days' treatment (16 to 27 days). Moderate fever
      was observed only once, in a patient with profound neutropenia. A complete
      recovery of blood cell count was noted in all cases, 5 to 9 days upon
      discontinuation of fusidic acid. A sternal bone-marrow aspiration was performed
      in 4 cases, showing normocellularity or hypercellularity in two cases, and
      moderate hypoplasia of granulocytic cells. The respective roles of other
      treatments are discussed. Overall, these five cases suggest that reversible
      granulocytopenia can be caused by protracted treatment with fusidic acid.
      Although nine different associated drugs could also have been involved in four
      patients, the causal relationship was less suggestive for three of them due to
      chronological events. In other cases, the drugs never or very rarely caused
      neutropenia. Finally, the possibility of vancomycin-induced neutropenia cannot be
      excluded in one case.

PMID- 8571284
TI  - [Extrapyramidal disorders induced by veralipride (Agreal). Apropos of 5 cases].
AB  - Veralipride is a substituted benzamide which is used for the treatment of
      menopausal hot flushes. We report five cases with extrapyramidal disorders
      associated to a treatment with this drug for which the neuroleptic activity
      resulting from an interaction with D2 receptors is not always known by
      prescribers. One case consisted of acute dyskinesias and four of parkinsonian
      syndromes, one of these being associated with tardive dyskinesia. In these four
      cases, dosing recommendations were not respected.

PMID- 8571285
TI  - [Adverse drug effect notifications by nurses and comparison with cases reported
      by physicians].
AB  - The aim of the present study was to investigate the characteristics of adverse
      drug reactions reported by hospital doctors and nurses from Toulouse University
      Hospital between 1992 and 1993. During these two years, doctors and nurses
      reported 1498 and 164 adverse drug reactions respectively. Nurses reported
      significantly more cutaneous side effects than doctors (50 vs 24 per cent).
      Doctors reported significantly more neuropsychiatric, haematologic, hepatic or
      renal side effects than nurses. Imputability (causal relation) score of adverse
      drug reactions given by nurses was higher than that of doctors: nurses reported
      more observations with imputability equal to I3 (likely: 55 vs 46 per cent) and
      less with imputability equal to I1 (doubtful: 3 vs 23 per cent). Serious side
      effects (as defined by WHO) were more often seen by doctors (19 per cent) than by
      nurses (10 per cent). The more frequently suspected drugs were antiinfectious
      agents (35 per cent) and analgesics (7 per cent) for nurses, and neurotropic
      drugs (23 per cent) for doctors. Side effects reported by nurses were mainly
      observed after parenteral administration (48 per cent) whereas doctors reported
      mostly side effects seen after oral route (66 per cent). This study underlines
      the characteristics of adverse drug reactions which can be reported by nurses.

PMID- 8571286
TI  - [Pharmacovigilance seen by a selected group of general practitioners and of
      residents in the Midi-Pyrenees region].
AB  - The attitude of general practitioners (GPs) to the drug surveillance system and
      the sources of information on drugs were assessed by a postal questionnaire sent
      to a sample of 600 GPs in the Midi-Pyrenees area. The results were compared to
      those obtained in a sample of young residents in the Toulouse University
      Hospital. The response rate of the GPs was 39.0 per cent (residents: 44.7 per
      cent). The lack of reporting was important in GPs (53.4 per cent) as well as in
      residents (52.6 per cent). In comparison with residents, GPs often did not know
      where and how notify adverse drug reactions (ADR) (8.0 per cent vs 21.0 per cent,
      p < 0.05). GPs notified mainly to pharmaceutical manufacturer (86.6 per cent), to
      the Pharmacovigilance Centre (15.4 per cent) or to the Toxicology Centre (9.1 per
      cent). However, the Pharmacovigilance Centre was found to give the best response,
      with 90 per cent of satisfying answers, for 47.9 per cent of GP and 44.0 per cent
      of residents. Ten years after the law founding the ADR reporting scheme in
      France, drug surveillance structures are still poorly understood.

PMID- 8571287
TI  - [What kind of pharmacovigilance applies to drugs derived from blood?].

PMID- 8571288
TI  - [Could you give me this drug without prescription?].

PMID- 8571289
TI  - [Toxic differential diagnosis of drug-induced pancreatitis].

PMID- 8571290
TI  - [Adverse hematologic effects of ticlopidine].

PMID- 8571291
TI  - [Evaluation of reports on "pregnancy and drugs" received during a period of 39
      months by the Regional Pharmacovigilance Center, Lorraine (Nancy)].

PMID- 8571292
TI  - [Neonatal toxicity of naphazoline administrated during pregnancy].

PMID- 8571293
TI  - [Cutaneous application of monoxidil during pregnancy: hairy infant].

PMID- 8571294
TI  - [Arterial thrombosis in a patient after chemotherapy (BEP protocol) for extra
      gonadal dysgerminoma].

PMID- 8571295
TI  - [No cross hypersensitivity between molgramostim and filgrastime: apropos of a
      case].

PMID- 8571296
TI  - [Risk of intracerebral hematoma and profibrinolytic activity of isotretinoin].

PMID- 8571297
TI  - [Occurrence of anterior uveitis in a HIV patient treated with rifabutin,
      ethambutol, clarithromycin].

PMID- 8571298
TI  - [Hypersensitivity to Sintrom, caused by cochineal red A].

PMID- 8571299
TI  - [Immunoallergic vasculitis: a new adverse effect of guanidine?].

PMID- 8571300
TI  - A case of phenytoin-alcohol interaction.

PMID- 8571301
TI  - [Moclobemide poisoning].

PMID- 8571302
TI  - [Paracetamol and leukocytoclastic vasculitis: apropos of a case].

PMID- 8571303
TI  - The alpha 2 beta 1 integrin: a collagen receptor on platelets and other cells.

PMID- 8571304
TI  - Molecular study of Glanzmann thrombasthenia in 3 patients issued from 2 different
      families.
AB  - In an effort to further understand Glanzmann thrombasthenia (GT) 3 patients from
      2 different families were studied. After biochemical and immunological analysis
      these patients were classified as type I. We observed in the first family a new
      restriction site for Stu I in exon II of the glycoprotein (GP) IIIa gene caused
      by a homozygous nonsense mutation: 62 Arg to stop codon. The parents were
      heterozygotes for this mutation. We found in the second family a previously
      described nonsense mutation: 584 Arg to stop codon in exon 17 of the GPIIb gene.
      The father and his two affected sons were heterozygous for this genetic defect.
      This mutation 62 Arg to stop codon is a new description of a genetic defect
      associated with GT. Furthermore, the discovery of the same mutation in 3 affected
      families from different ethnic groups raises the possibility of either a hot spot
      mutation in the CG dinucleotide region of GPIIb gene, or an ancient mutant allele
      present in diffuse populations at a relatively high frequency.

PMID- 8571305
TI  - Fibrin D-dimer, haemostatic factors and peripheral arterial disease.
AB  - Several haemostatic factors have been shown to have a predictive role in
      cardiovascular disease, although their relationship with prevalent peripheral
      arterial disease is not well reported. Using a random sample of 1592 men and
      women aged 55-74 years from Edinburgh, Scotland, we examined the relationship of
      von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and fibrin D
      dimer antigens and factor VII activity to peripheral arterial disease. t-PA
      antigen and fibrin D-dimer showed significant linear trends of increased levels
      with increasing severity of disease in both sexes (p < or = 0.01) and vWF showed
      a similar pattern in men only (p < or = 0.01). On multivariate analysis, fibrin D
      dimer was independently related to the risk of intermittent claudication (p < or
      = 0.01) and, among men, to the extent of arterial narrowing in the lower limb, as
      measured by the ankle brachial pressure index, (ABPI) (p < or = 0.001). These
      results are further evidence of a role for intravascular fibrin deposition in the
      development of peripheral atherosclerosis.

PMID- 8571306
TI  - Evaluation of a soluble fibrin assay in patients with suspected deep vein
      thrombosis.
AB  - BACKGROUND: The objective of this study was to determine the clinical utility of
      an enzyme immunoassay (EIA) for soluble fibrin in patients with clinically
      suspected deep vein thrombosis (DVT). METHODS AND RESULTS: 101 unselected
      patients with clinically suspected DVT underwent blood sampling for measurement
      of plasma levels of soluble fibrin, and objective testing for DVT. According to
      results of the objective tests, patients were classified as DVT-positive (n = 34)
      or DVT-negative (n = 67). Using different cut-points of soluble fibrin results,
      the sensitivities, specificities, positive and negative predictive values of the
      soluble fibrin assay were calculated. A soluble fibrin result of < or = 0.75
      mg/ml showed a sensitivity and negative predictive value of 100%, and a
      specificity of 17.9% for DVT, a soluble fibrin result of < or = 1.40 mg/ml showed
      a sensitivity of 91.2% and a negative predictive value of 93.6%, and a
      specificity of 65.7% for DVT, whereas a soluble fibrin result of < or = 8.0 mg/ml
      showed a specificity and positive predictive value of 100% for DVT. CONCLUSIONS:
      This study demonstrates that the soluble fibrin assay used in the study has
      potential clinical utility as a diagnostic test in patients with clinically
      suspected DVT and supports further evaluation of this assay.

PMID- 8571307
TI  - The 4G/5G genetic polymorphism in the promoter of the plasminogen activator
      inhibitor-1 (PAI-1) gene is associated with differences in plasma PAI-1 activity
      but not with risk of myocardial infarction in the ECTIM study. Etude CasTemoins
      de I'nfarctus du Mycocarde.
AB  - We have investigated the interrelationships of plasma PAI-1 activity, the PAI-1
      4G/5G polymorphism and risk of myocardial infarction (MI) in the ECTIM study, a
      case-control study of MI based in Belfast, Lille, Strasbourg and Toulouse. Mean
      PAI-1 levels in cases were similar across all centres but in controls, levels in
      the French centres were significantly higher. Only in Belfast were PAIl1 levels
      higher in cases (11.7 AU/ml) than controls (10.5 AU/ml). The PAI-1 4G allele
      frequency was similar in cases and controls (0.55 and 0.54). In all groups, 4G
      homozygotes had the highest mean plasma PAI-1 level (4G4G vs 5G5G; cases overall:
      14.2 vs 12.1AU/ml; controls overall: 15.0 vs 12.6AU/ml), with the heterozygotes
      generally intermediate. The data from Belfast are consistent with the literature
      implicating PAI-1 level as an MI risk factor. In ECTIM, the PAI-1 4G/5G
      polymorphism is not a genetic risk factor for MI but is associated with PAI-1
      activity. Thus homozygosity for the 4G allele may predispose to elevated PAI-1
      and impaired fibrinolysis, perhaps requiring interaction with other genetic or
      environmental factors to influence MI risk.

PMID- 8571308
TI  - Environmental and genetic factors in relation to elevated circulating levels of
      plasminogen activator inhibitor-1 in Caucasian patients with non-insulin
      dependent diabetes mellitus.
AB  - To investigate the interaction of metabolic and genetic factors in relation to
      PAI-1, genotype was determined at a 4G/5G polymorphism in the PAI-1 gene promoter
      and a Hind III RFLP of the PAI-1 gene in 189 Caucasian NIDDM patients. PAI-1
      levels were equivalent in each genotype group and PAI-1 activity correlated with
      fasting insulin (r=0.45), triglyceride (r=0.39) body mass index (r=0.44),
      cholesterol (r=0.17) and glucose (r=0.15). The regression slope (B) of PAI-1
      activity on triglycerides was steeper in the 4G/4G group than the other two
      groups: 4G/4G B = 0.91, r = 0.62; 4G/5G B = 0.36, r=0.27; 5G/5G B=0.31, r=0.29
      (difference between slopes p=0.02) and the association between PAI-1 activity and
      glucose remained only in the 4G/4G group (r=0.35). These results confirm the
      association of PAI-1 levels with the features of insulin resistance and indicate
      that the association between PAI-1 levels and both triglyceride and glucose is
      influenced by genotype in the region of PAI-1 gene promoter.

PMID- 8571309
TI  - Outcome of disseminated intravascular coagulation in relation to the score when
      treatment was begun. Mie DIC Study Group.
AB  - We examined 395 patients with disseminated intravascular coagulation (DIC)
      divided into two groups: non-leukemic and leukemic. In 58% of the patients as a
      whole, treatment of DIC resulted in complete or partial remission, while
      exacerbation and death occurred in 31%. The efficacy of DIC treatment in the non
      leukemic group was less than that in the leukemic group, indicating that the
      outcome of DIC depended, in part, on the underlying disease. We examined
      hemostatic indicators in relation to DIC score: prothrombin time (PT) ratio, FDP,
      platelet count, and fibrinogen levels were found to be important indicators for
      the diagnosis of DIC, but not for Pre-DIC. Plasma levels of fibrin-D-dimer,
      thrombin-antithrombin complex (TAT), and plasmin-plasmin inhibitor complex (PPIC)
      were significantly increased in pre-DIC. The efficacy of treatment in relation to
      the DIC score when the treatment was begun showed that greater efficacy was
      achieved in pre-DIC than in DIC patients. The outcome was poorer with increasing
      DIC score, suggesting that early diagnosis and early treatment are important. On
      examining the relationship between outcome and hemostatic indicators, we found
      that the PT ratio and the levels of antithrombin, plasminogen, PPIC, the PPIC/TAT
      ratio, and thrombomodulin were related to outcome, suggesting that very high
      consumption of blood coagulation factors, liver dysfunction, hypofibrinolysis, or
      organ failure caused a poor outcome. Although the outcome in DIC patients may not
      depend substantially on plasma levels of TAT and fibrin-D-dimer, we can use these
      indicators to treat DIC patients at an early stage.

PMID- 8571310
TI  - Effect of fibrinogen substitution in afibrinogenemia on hemorheology and platelet
      function.
AB  - Fibrinogen substitution can correct bleeding in afibrinogenemia. We assessed the
      effect of fibrinogen substitution in a patient lacking immunoreactive fibrinogen.
      Fibrinogen and thrombin time were not measurable before, but became detectable
      within 30 min after substitution, parallelled by an increase in ADP-induced
      platelet aggregation from < 10% to 32%. Platelet adhesion, measured by Stagnation
      Point Flow Adhesio- Aggregometry, was not detectable prior to substitution but
      attained normal values thereafter. Scanning electron microscopy of adhering
      platelets revealed pseudopodia protrusion and spreading. Morphometry revealed two
      populations of spread platelets one of which demonstrated inhibited spreading as
      compared to healthy controls. Immunoelectron microscopy revealed normal
      GPIIb/IIIa receptor expression, both before and after substitution. Dynamic and
      kinematic viscosity of plasma and whole blood remained below the 99.9% confidence
      border of a healthy control group. In afibrinogenemia fibrinogen levels as low as
      10% of normal concentration sufficed to normalize coagulation, platelet adhesion,
      and, partially, spreading.

PMID- 8571311
TI  - Circulating dermatan sulfate and heparan sulfate/heparin proteoglycans in
      children undergoing liver transplantation.
AB  - The liver produces dermatan sulfate (DS), heparan sulfate (HS) and heparin
      glycosaminoglycans (GAG) and in the presence of hepatic disease, tissue levels of
      the DS GAG increase dramatically. We hypothesized that in children undergoing
      liver transplantation plasma levels of DS would be increased. Plasma from
      children undergoing liver transplantation were tested preoperative, intra
      operative and post operative at 24-48 h, and 1-3 weeks. Fluctuating levels of DS,
      HS and heparin anticoagulant activity were detected at all timepoints. The
      anticoagulant activity was purified and gel chromatography of the material
      displayed a mean Mr 110,000 D. Reductive elimination decreased the mean Mr 24,000
      D indicating the activity resides on a proteoglycan (PG). The purified material
      was subjected to further chromatography and two peaks of anticoagulant activity
      resolved, compatible with at least two separate PGs, one with DS GAG chains and
      the additional PG(s) with HS and heparin GAG chains.

PMID- 8571312
TI  - "In vitro" and in animal model studies on a double virus-inactivated factor VIII
      concentrate.
AB  - To improve the safety of plasma derived factor VIII (FVIII) concentrate, we
      introduced a final super heat treatment (100 degrees C for 30 min) as additional
      virus inactivation step applied to a lyophilized, highly purified FVIII
      concentrate (100 IU/mg of proteins) already virus inactivated using the
      solvent/detergent (S/D) method during the manufacturing process. The efficiency
      of the super heat treatment was demonstrated in inactivating two non-lipid
      enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII
      procoagulant activity during the super heat treatment was of about 15%, estimated
      both by clotting and chromogenic assays. No substantial changes were observed in
      physical, biochemical and immunological characteristics of the heat treated FVIII
      concentrate in comparison with those of the FVIII before heat treatment.

PMID- 8571313
TI  - Diagnostic efficacy of plasma urokinase-type plasminogen activator and
      plasminogen activator inhibitor-2 in differentiation of hepatocellular carcinoma
      from cirrhosis.
AB  - We determined the plasma antigen levels of urokinase-type plasminogen activator(u
      PA) and plasminogen activator inhibitor 2(PAI-2) in 41 patients with
      hepatocellular carcinoma and 28 patients with different stages of liver
      cirrhosis. No significant differences of u-PA and PAI-2 levels were calculated
      between the two groups of tumor patients (HCC) and liver cirrhosis without tumor
      (non-HCC). Within both study groups, no significant differences were found in u
      PA and PAI-2 levels of the different Child categories. Discriminative functions
      of both u-PA and PAI-2 (total error count estimates of 43.1% and 43.6%,
      respectively), were low compared to that (29.0%) of alpha-fetoprotein (AFP). The
      combinations of AFP and u-PA lowered the total error rate (21.9%) more than that
      of each marker alone. However, whether plasma u-PA and PAI-2 may be considered as
      a risk factor further investigation was needed and our findings raise the
      question as to whether these markers could be considered as useful screening
      markers for earlier detection of HCC in liver cirrhosis because discriminant
      functions of u-PA and PAI-2 were not significant. Sensitivities and specificities
      of u-PA and PAI-2 were also not high enough, resulting in the ranges of total
      diagnostic efficiency from 43% to 50%, and, from 49% to 63%, respectively, at
      different cut-off values. No direct relationship was detected between AFP and u
      PA, between AFP and PAI-2, and between u-PA and PAI-2.

PMID- 8571314
TI  - The polymerase chain reaction with sequence specific primers for the detection of
      the factor V mutation associated with activated protein C resistance.
AB  - The prevalence of the Factor V (FV) mutation associated with activated protein C
      resistance (FV Leiden) and its significance as a genetic risk factor for venous
      thrombosis have necessitated the development of a simple, rapid, and accurate
      assay for its detection. The polymerase chain reaction with sequence specific
      primers (PCR-SSP) provides a powerful technique for the discrimination of alleles
      resulting from single base substitutions. PCR amplification was performed using a
      sense primer complementary to both FV alleles coupled with either of two
      antisense allele specific primers, one complementary to the normal FV allele and
      one complementary to the FV Leiden allele. PCR conditions were developed that
      favored amplification only in the case of perfect complementation between
      template DNA and allele specific primer. The FV genotype was assigned based on
      whether or not each allele specific primer set produced an amplified product.
      Assignment of genotypes correlated 100% with those determined by the method of
      PCR amplification followed by Mn1I digestion. PCR-SSP allows the rapid and
      accurate identification of carriers of the Factor V Leiden mutation by a simple
      PCR reaction without the need for the usual post-amplification specificity step.

PMID- 8571315
TI  - Antithrombotic action of endogenous porcine protein C activated with a latent
      porcine thrombin preparation.
AB  - Endogenously activated protein C is evaluated for antithrombotic activity in
      porcine carotid arteries subjected to mechanical trauma. Protein C is activated
      by intravenous administration of guanidinobenzoyl-thrombin, which binds to
      thrombomodulin and there deacylates to yield thrombin. The bound, transiently
      active thrombin yields a peak of anticoagulant activity between 5 and 10 min
      after infusion of the latent thrombin. Inhibition of thrombin binding in vivo by
      co-infusing and active-site-blocked thrombin preparation elicits acute and lethal
      systemic thrombosis. Nearly occlusive platelet thrombosis, which occurs within 30
      min of crushing 1 cm segments of carotid arteries with a standard hemostat, is
      blocked by endogenous protein C activation initiated 2 min before the crush
      injury. It is concluded that activated protein C blocks thrombosis is deeply
      injured musculo-elastic arteries, and that activation of latent thrombin bound to
      thrombomodulin in vivo is a practical means for delivery of pharmacologically
      effective concentrations of activated protein C.

PMID- 8571316
TI  - Characterization of the structural requirements for a carbohydrate based
      anticoagulant with a reduced risk of inducing the immunological type of heparin
      associated thrombocytopenia.
AB  - HAT is the most frequent drug induced immune-thrombocytopenia. We recently
      identified multimolecular PF4/heparin complexes as the major antigen. In order to
      evaluate the structural requirements for formation of the antigenic complex, we
      chemically synthesized 13 glucan sulfates and used 5 heparin fractions (2.4-4.8
      kD) and a synthesized pentasaccharide, representing the antithrombin III binding
      sequence of heparin, for further characterize the HAT antigen. In the presence of
      glucan sulfates and heparin, HAT antibodies caused platelet activation typically
      at low but not at high concentrations, as measured by 14C-5HT release. The
      concentration range giving the activation pattern depended on the degree of
      sulfation (DS) and molecular weight (MW) of the glucan sulfates but not on the
      type of glycosidic linkage of a polysaccharide. With linear glucan sulfates with
      a chain length of 35 monosaccharides, the critical DS to form the HAT antigen
      ranged between 0.60 and 1.20. Glycosidic branched glucan sulfates were able to
      form the HAT antigen at a lower DS and a lower MW than linear glucan sulfates.
      Platelet activation by HAT-antibodies in the presence of linear curdlan sulfate
      fractions was dependent on their MW. At a low concentration (0.01 microM) medium
      size fractions (60 kD) caused platelet activation but neither small (12 kD) nor
      large fractions ( > 150 kD) did. At higher concentrations (2 microM) the opposite
      reaction pattern was observed. In the case of heparin, the optimal chain length
      for forming the HAT antigen is a hexadecasaccharide (4.8 kD). Antigen generation
      decreased with larger and smaller fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8571317
TI  - A collaborative study of proposed European Pharmacopoeia reference preparations
      of low molecular mass heparin.
AB  - A European collaborative study, in which 16 laboratories participated, was
      carried out to assess the performance of the European Pharmacopoeia (EP)
      monograph methods for anticoagulant activities (anti-Xa and anti-IIa assays) of
      low molecular mass (LMM) heparin and to assess the suitability of six candidate
      materials as the EP working standard for LMM heparin. There was good
      interlaboratory agreement for both types of assays as indicated by most gcy's
      being less than 10%, indicating acceptable performance of the EP assay methods.
      All the candidate preparations gave dose-response curves parallel to the 1st
      International Standard for Low Molecular Weight heparin and to each other. All
      preparations, possibly with the exception of E and F, gave similar performance as
      measured by interlaboratory agreement and would be suitable as working standards.
      Based on these data, preparations A, B, C and D have been established by the EP
      as official EP Biological Reference Preparations and they will be issued as
      successive batches.

PMID- 8571318
TI  - The International and "NIH" units for thrombin--how do they compare?
AB  - The current International Standard (IS) for alpha-thrombin was established in
      1991. It was related in unitage with the 1st IS for Thrombin established in 1975
      and contains 100 IU of thrombin activity. The National Institute of Health (NIH)
      standard (Lot J) is in common use for the calibration of commercial thrombin
      reagents and this study reports on a comparison of the thrombin units defined by
      these 2 standards. This study has indicated that one "NIH" unit is equivalent to
      1.1 to 1.3 IU of thrombin, depending on the influence of PEG in the assay. A
      unitage ratio figure of 1.15 was recommended following analysis of data obtained
      in the presence and absence of PEG in the comparative assays. This was confirmed
      by amidolytic assay data.

PMID- 8571319
TI  - Antigen and functional expression of tissue factor in endotoxin stimulated U937
      cells: regulation of activity by calcium ionophore A23187.
AB  - Tissue Factor (TF) is a transmembrane glycoprotein that serves as cofactor for
      Factor VII (FVII) in the initiation of blood coagulation and that is
      differentially expressed in a number of cell types, being constitutively
      expressed in some and inducible in others. We studied the localization and the
      functional activity of TF in monocytic leukemia U937 cells at different time
      intervals after lipopolysaccharides (LPS) stimulation, and the effect of calcium
      ionophore on the surface expressed TF. Exposure of U937 cells to 10 micrograms/ml
      LPS resulted in a time dependent increase of TF expression that reached a maximum
      at 12 h for TF antigen and at 24 h for TF activity. Blocking of surface TF with
      inhibitory anti-TF antibody abolished > 93% of the activity of lysed cells
      stimulated for 24 h, while it blocked only 80% of the activity in lysed cells
      stimulated for 12 h suggesting that at that time about 20% of TF is not
      accessible for the antibody. Even at 24 h when the specific activity of surface
      expressed TF is 5.5 times higher than at 12 h, this specific activity is still 10
      fold lower than that of TF in lysed cells. Addition of Ca++ ionophore A23187 to
      LPS stimulated cells resulted in a fast increase of TF activity that was
      dependent on the dose of ionophore, on the extracellular Ca++ concentration and
      on the time that the cells had been incubated with LPS.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8571320
TI  - Kinetics of the inhibition of tissue factor-factor VIIa by tissue factor pathway
      inhibitor.
AB  - Tissue factor-factor VIIa catalysed activation of factor IX is inhibited by the
      complex of tissue factor pathway inhibitor (TFPI) and factor Xa. At present, no
      information is available as to what extent the kinetics of complex formation
      between TFPI and factor Xa during factor X activation contribute to the overall
      rate of inactivation of the factor X converting complex. We have determined the
      kinetic parameters of the individual reactions, i.e. factor X activation,
      formation of the TFPI-factor Xa complex, and inactivation of tissue factor-factor
      VIIa by the TFPI-factor Xa complex. We modelled the overall reaction by assuming
      a two-step reaction: factor Xa generated by tissue factor-factor VIIa forms a
      reversible complex with TFPI and in the second step this complex forms a
      reversible quaternary complex with tissue factor-factor VIIa. The validity of the
      model was demonstrated by analysis of factor Xa generation curves in the presence
      of TFPI. Independently determined constants for factor X activation (kcat = 12 s
      1, Km = 70 nM) and inhibition of tissue factor-factor VIIa by TFPI-factor Xa
      complex (rate constant of inhibition of 1.1 x 10(8) M-1S-1) were used. The
      association rate constant of the formation of the TFPI-factor Xa complex was
      estimated by fitting the model to the data.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8571321
TI  - Residence time in niches of stagnant flow determines fibrin clot formation in an
      arterial branching model--detailed flow analysis and experimental results.
AB  - Deposition of blood components in branching flow has been investigated primarily
      with regard to platelets. We instead examined thrombin-induced fibrin clot
      formation in separated laminar as well as turbulent branching flow. The most
      rapid clot growth and largest clot was obtained at the lowest inflow rate.
      Increased inflow reduced the clot size and turbulence completely prevented clot
      formation. Examination of corresponding flow conditions revealed the
      recirculation zone in laminar flow to be characterized by two stationary,
      counterrotating vortices. Niches of stagnant flow, exhibiting long residence
      times, low wall shear rates and characterized by convergent flow, were spared
      between the bulk flow and these vortices. Here, fibrin clot growth continued even
      when shear rates were increased more than 100-fold. Our results indicate that, in
      branching flow, the long residence times and convergent flow characteristic of
      flow niches rather than shear rate are critical for fibrin clot formation.

PMID- 8571322
TI  - A monoclonal antibody against a peptide sequence of fibrinogen gamma chain acts
      as an inhibitor of factor XIII-mediated crosslinking of human fibrin.
AB  - Recurrent hemorrhage has been reported in humans as a result of acquired antibody
      inhibitors which interfere with the crosslinking of fibrin by factor XIII. One
      type of these inhibitors (Type III) prevents activated factor XIII from acting on
      fibrin. We have generated an antifibrin monoclonal antibody, called mAb 4A5,
      which binds to a peptide sequence at the carboxyl-terminus of human fibrinogen
      gamma-chains. MAb 4A5 acts like a Type III inhibitor and prevents proper factor
      XIII-mediated crosslinking. Pre-incubation of fibrinogen or pooled human plasma
      with mAb 4A5, but not mAb D2 (specific for the carboxyl terminus of fibrin alpha
      chains), resulted in clots which are soluble in either 5 M urea or 1%
      monochloroacetic acid. SDS-PAGE and immunoblotting analysis of these clots
      confirmed that mAb 4A5 inhibited gamma-chain crosslinking in plasma clots and
      fibrin clots. Results from a factor XIII activity assay demonstrated that
      biotinylcadaverine crosslinking into fibrin by factor XIII could be inhibited by
      mAb 4A5 but not mAb D2, arguing that mAb 4A5 acted by binding the crosslinking
      site of factor XIII. Studies of the immunoreactivity of these mAbs with 12
      different animal species showed that the gamma-chain epitope recognized by mAb
      4A5 was more conserved than the alpha-chain epitope recognized by mAb D2. The
      species fibrinogens, recognized by mAb 4A5 in binding assays, also showed
      impaired crosslinking when mAb 4A5 was present during the clotting reaction

PMID- 8571323
TI  - Changes in haemostatic variables induced by oral contraceptives containing 50
      micrograms or 30 micrograms oestrogen: absence of dose-dependent effect on PAI-1
      activity.
AB  - Several studies have suggested a dose-response relation between the oestrogen
      content of oral contraceptive (OC) and the risk of both venous thrombosis and
      arterial disease, when oestrogen doses were higher than 50 micrograms. However,
      there is no clear epidemiological evidence for a decrease in thrombotic risk with
      formulations containing less than 50 micrograms oestrogen. Therefore, we
      investigated haemostatic variables in users of OC containing either 30 micrograms
      (35 women) or 50 micrograms (29 women) ethinyl estradiol as compared with non
      users (64 women) matched for age and smoking status. Mean values of antithrombin
      activity were significantly lower in 30 micrograms or 50 micrograms oestrogen
      users than in non users (96% and 98% vs 105%, respectively, p < 0.001), but they
      were not significantly different between the two groups of OC users. There was a
      significant increase in mean values of factor VII antigen in women taking either
      30 micrograms or 50 micrograms oestrogen as compared with non users (96% and 101%
      vs 85%, respectively, p < 0.005). Although the difference between both groups of
      OC users was not significant, a positive linear trend in factor VII levels was
      observed within the 0-50 micrograms oestrogen range (p < 0.001). Mean levels of
      fibrinogen were slightly higher in 30 micrograms or 50 micrograms oestrogen users
      than in non users (2.71, 2.66 g/l vs 2.55 g/l, respectively), but there was no
      significant difference between the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8571324
TI  - Plasminogen activator inhibitor-1 mRNA is induced by hemorrhage in endothelial
      and mesothelial cells of the rat liver.
AB  - We have recently shown that plasminogen activator inhibitor-1 (PAI-1) mRNA is
      elevated after hemorrhage in various tissues including liver. In this study, we
      set out to identify the cell types in the liver that are responsible for the
      increase in PAI-1 mRNA after hemorrhage using in situ reverse transcription
      polymerase chain reaction (in situ RT-PCR). Male Sprague-Dawley rats were
      cannulated and subjected to a 20 ml/kg hemorrhage within 3 min or 300
      micrograms/kg of endotoxin. Four hours later, the livers were harvested, fixed,
      frozen, and sectioned. RT-PCR showed an increase of PAI-1 mRNA in liver 4 h after
      hemorrhage or endotoxin-treatment. Standard in situ hybridization could not
      detect PAI-1 mRNA in the livers of either the hemorrhage, endotoxin, or control
      groups. However, in situ RT-PCR detected PAI-1 mRNA in vascular endothelial cells
      and capsular mesothelial cells, but not in hepatocytes, in both the hemorrhage
      and endotoxin groups. No signal was found in the control rats, or when the
      experimental protocol was modified to 1) omit the RT step, 2) precede the RT step
      with RNA digestion, or 3) use an irrelevant probe. These results demonstrate that
      hemorrhage induces PAI-1 mRNA in endothelial and mesothelial cells of liver.

PMID- 8571325
TI  - Human anti-streptokinase antibodies induce platelet aggregation in an Fc receptor
      (CD32) dependent manner.
AB  - Exposure to streptokinase (SK) elicits anti-SK antibodies (Abs), which inhibit
      fibrinolysis and induce platelet aggregation. The mechanism of the latter is not
      fully understood, although it seems to involve platelet binding by a plasminogen
      streptokinase and anti-SK ternary complex. Anti-SK Abs were purified by affinity
      chromatography from serum of patients having received SK for acute myocardial
      infarction (AMI), and were shown to be of the IgG type. Their effects were
      studied with (i) human platelets in citrated plasma in the presence of SK or
      acetylated plasminogen-SK activator complex (APSAC), and (ii) in washed
      platelets, resuspended in Tyrode buffer after lowering the ionic strength, in the
      presence of APSAC (which provides both SK and plasminogen). An antibody
      concentration-response curve was obtained, showing a plateau in the presence of
      0.1 mg/ml IgG. By increasing the concentration of APSAC, we obtained a unimodal
      response curve, the optimal concentration of APSAC being 0.05 U/ml. Aggregation
      was suppressed by chelating calcium with EDTA, blocking fibrinogen binding by the
      synthetic peptide Arg-Gly-Asp-Ser (RGDS), and raising intraplatelet cAMP with
      Iloprost (a prostacyclin analogue). Aggregation required the interaction of the
      anti-SK Ab Fc domain with the platelet Fc-gamma receptor type II, also known as
      CD32, since: (i) it was blocked by the monoclonal antibody IV-3 directed against
      CD32, (ii) it did not occur with F(ab)'2 fragments, which block the response to
      the intact IgG. The clinical relevance of these platelet-activating anti-SK
      antibodies remains to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8571326
TI  - Correlation of specific platelet activation markers with carotid arterial wall
      thickness.
AB  - Many studies have shown increased platelet activation in patients with coronary
      artery, cerebrovascular and peripheral vascular diseases. However, the temporal
      relationship between platelet activation and arterial atherosclerosis is unclear.
      To answer this basic question, we measured the plasma concentrations of two
      specific platelet activation markers, beta-thromboglobulin (beta TG) and platelet
      factor 4 (PF4) in 459 cases with increased carotid arterial wall thickness and
      459 age-, sex-and race-matched controls selected from a cohort of 15,800 men and
      women, aged 45-64 who participated in the Atherosclerosis Risk in Communities
      Study. These participants had no acute vascular symptoms or known cardiovascular
      disease. The mean values of beta TG and PF4 were significantly higher in cases
      than in controls. However, when analyzed by quartiles using conditional logistic
      regression, only beta TG exhibited a significant association with carotid wall
      thickness, while PF4 did not. The odds ratio (OR) determined by multivariate
      logistic regression analysis was significantly higher for the uppermost quartile
      of beta TG (OR=1.7, 95% CI 1.1-2.5) compared to the lower 3 quartiles. This OR
      was 2.3 in white men (95% CI 1.2-4.2), 1.4 in white women (95% CI 0.6-3.0) and
      1.0 in blacks (95% CI 0.4-2.5). This study indicates that plasma beta TG may be
      useful as a marker for early atherosclerosis in middle aged adults, particularly
      in white men. It also suggests that platelet activation has an independent role
      in the pathogenesis of atherosclerosis, although the possibility that this may be
      a response to carotid atherosclerosis cannot be excluded.

PMID- 8571327
TI  - Inherited platelet delta-storage pool disease in dogs causing severe bleeding: an
      animal model for a specific ADP deficiency.
AB  - The nature of a disorder producing moderate to severe bleeding after minor
      trauma, venipuncture, and surgery was studied in 3 families of American cocker
      spaniel dogs. In the 5 affected dogs tested, platelet counts and measurements of
      plasma coagulant function and von Willebrand factor were normal. However,
      bleeding times were prolonged in 4 of the 5 affected dogs tested, and platelet
      aggregation in response to ADP and collagen was consistently abnormal in 3,
      suggesting that the bleeding disorder was due to abnormal platelet function.
      Measurements of 14C-serotonin uptake and retention by the affected platelets were
      normal. However, their ADP content was decreased, while their ATP content was
      normal, resulting in a mean ATP/ADP ratio of 8.32, compared to a mean ratio of
      1.9 in normal canine platelets. Electron microscopy revealed that the number and
      appearance of the dense granules in the affected platelets were indistinguishable
      from those of normal controls. These studies suggest that this bleeding disorder
      results from a deficient delta-granule storage pool of ADP; given the normal
      serotonin uptake and retention by affected platelets and the apparently normal
      number of dense granules, the ADP deficiency may be the consequence of a
      selective defect in delta-granule ADP transport. Additional studies of this
      unique platelet disorder will provide an opportunity to understand the mechanism
      of adenine nucleotide storage in platelet delta-granules.

PMID- 8571329
TI  - Prolonged expression of procoagulant activity of human platelets degranulated by
      thrombin.
AB  - Platelets are exposed to thrombin when they take part in arterial thrombus
      formation, and they may return to the circulation when they are freed by
      fibrinolysis and dislodged by flowing blood. Thrombin causes the expression of
      procoagulant activity on platelets, and if this activity persists, the
      recirculating platelets may contribute to subsequent thrombosis. We have
      developed techniques to degranulate human platelets by treatment with thrombin,
      and recover then as single, discrete platelets that aggregate in response to both
      weak and strong agonists. In the present study we examined the duration of
      procoagulant activity on the surface of thrombin-degranulated platelets by two
      methods: a prothrombinase assay, and the binding of 125I-labeled annexin. Control
      platelets generated 0.9 +/- 0.4 U thrombin per 10(7) platelets in 15 min.
      Suspensions of thrombin-degranulated platelets formed 5.4 +/- 0.1 U thrombin per
      10(7) platelets in this time. Binding of 125I-annexin V was also greater with
      thrombin-treated platelets than with control platelets (controls: 1.7 +/- 0.1 ng
      annexin/10(7) platelets; thrombin-degranulated platelets: 6.8 +/- 0.2 ng
      annexin/10(7) platelets). With thrombin-degranulated platelets, increased
      procoagulant activity and annexin binding persisted for at least 4 h after
      degranulation and resuspension, indicating that the catalytic activity for the
      prothrombinase complex is not reversed during this time. These platelets
      maintained their ability to aggregate for 4 h, even in response to the weak
      agonist, ADP. Thus, platelets that have taken part in thrombus formation and
      returned to the circulation may contribute to the promotion of further thrombotic
      events because of the persistence of procoagulant activity on their surface.

PMID- 8571328
TI  - Interaction of echicetin with a high affinity thrombin binding site on platelet
      glycoprotein GPIb.
AB  - Echicetin, a protein isolated from Echis carinatus snake venom, inhibited
      platelet aggregation and secretion induced by low concentrations of thrombin ( <
      0.2 U/ml), by binding to platelet glycoprotein Ib (GPIb). The inhibition was not
      observed when the platelets were stimulated with higher concentrations of
      thrombin ( > 0.2 U/ml). Echicetin competed with thrombin for binding to the high
      affinity site on GPIb. Thrombin also inhibited 50% of the binding of 125I
      echicetin to the platelets.

PMID- 8571330
TI  - The effect of fibrin clots and clot-bound thrombin on the development of platelet
      procoagulant activity.
AB  - We tested different types of clot for their ability to provoke procoagulant
      activity in platelets: normal clots from platelet poor plasma (des AABB- or
      fibrin II clots), similar clots in which the adsorbed thrombin has been inhibited
      by hirudin, and clots obtained by the action of two snake venom enzymes that
      release only fibrinopeptide A (des AA- or fibrin I clots). Analogous clots from
      fibrinogen solutions were also tested. In platelet rich plasma (PRP), where
      platelet coagulant phospholipids (PCP) are rate limiting for thrombin generation,
      the addition of any type of clot enhances the generation of thrombin thus it
      induces the appearance of PCP. Clots containing active adsorbed thrombin are the
      most potent ones in this respect. Lactate dehydrogenase (LDH) levels do not
      increase in the course of the thrombin generation so the platelets are not
      damaged in the process. Non-centrifugable PCP could be demonstrated to appear
      during the process, so the production of procoagulant phospholipid microparticles
      must be part of the mechanism. Membrane transbilayer phosphatidyl serine movement
      (flip-flop) can not be demonstrated in PRP as the activated platelets are caught
      in the emerging clot. In order to demonstrate flip-flop, we tried to investigate
      the influence of clots on washed platelets. However, contrary to platelets in a
      plasma milieu, isolated platelets are damaged by fibrin clots, especially in the
      presence of thrombin, as can be judged from the appearance of LDH. We conclude
      that, in PRP, clots induce the appearance of PCP from platelets by vesiculation,
      possibly accompanied by flip-flop and that thrombin accelerates the process but
      is not an absolute requirement.

PMID- 8571331
TI  - Sod and GSH inhibit the high glucose-induced oxidative damage and the PDGF
      increased secretion in cultured human endothelial cells.
AB  - Poor control of blood glucose has been established as a key pathogenetic
      mechanism in the vascular complications of diabetes. It has been reported that
      glucose may autooxidize generating free radicals which have been suggested to
      delay proliferation, to modify mobility, to influence platelet-derived growth
      factor and other secretory protein production in a variety of cell systems.
      Platelet-derived growth factor, in turn, may induce proliferation and migration
      of vascular smooth muscle cells and thus play a role in atherogenesis. In the
      present study the effects of antioxidants on the high glucose-dependent oxidative
      cell damage and increased platelet-derived growth factor secretion have been
      investigated using cultured human endothelial cells. Our findings show that
      rising the glucose concentration in the culture medium from 5 mM to 20 mM,
      increased the production of free radicals cell damage markers, such as
      malondialdehyde and conjugated dienes, as well as the production of platelet
      derived growth factor. The addition of superoxide dismutase or glutathione
      prevents both such effects. These results suggest that antioxidants may be a
      helpful therapeutic adjuvant to reduce the vascular complications of diabetes.

PMID- 8571332
TI  - Aurintricarboxylic acid reduces platelet deposition in stenosed and endothelially
      injured rabbit carotid arteries more effectively than other antiplatelet
      interventions.
AB  - In the present study we tested the effects of different antithrombotic
      interventions on platelet deposition in experimentally-stenotic rabbit carotid
      arteries with endothelial injury. Platelet deposition, quantitated by labeling
      autologous platelets with 111In-oxine, was significantly reduced compared to
      control animals by all interventions tested, i.e., R 68070, a drug with
      thromboxane A2 synthase and receptor blocking properties, BN 52021, a PAF
      receptor antagonist, aurintricarboxylic acid (ATA), an inhibitor of platelet
      glycoprotein (Gp) Ib/von Willebrand factor (vWf) interaction, AZ-1, a monoclonal
      antibody against rabbit GP IIb/IIIa, the platelet receptor for fibrinogen, and AP
      1, a monoclonal antibody against rabbit tissue factor. ATA was significantly more
      effective than all the other interventions in reducing platelet deposition in the
      stenotic vessels. We conclude that inhibition of Gp Ib/vWf interaction may be a
      more suitable target for antithrombotic therapy under conditions of high shear
      stress, like those produced in this model.

PMID- 8571333
TI  - Thrombin prevents the expression of inducible nitric oxide synthase in vascular
      smooth muscle cells by a proteolytically-activated thrombin receptor.
AB  - Proteolytically active forms of thrombin ( alpha- and gamma-thrombin) and
      thrombin receptor peptides inhibited the release of nitrite, a stable endproduct
      of nitric oxide, evoked by interleukin-1 beta (IL-1 beta ) in cultured vascular
      smooth muscle cells while proteolytically inactive forms [D-Phe-Pro-Arg
      chloromethyl ketone-alpha-thrombin (PPACK-alpha-thrombin) and
      diisopropylphosphoryl-alpha-thrombin (DIP-alpha-thrombin)] had either no or only
      minimal inhibitory effects. Under bioassay conditions, perfusates from columns
      containing IL-1 beta-activated vascular smooth muscle cells or cells treated with
      IL-1 beta plus PPACK-alpha-thrombin relaxed detector blood vessels. These
      relaxations were abolished by the inhibitor of nitric oxide synthesis, NG-nitro-L
      arginine. No relaxations were obtained with untreated cells or IL-1 beta-treated
      cells in the presence of alpha-thrombin. The expression of inducible nitric oxide
      synthase mRNA and protein in vascular smooth muscle cells by IL-1 beta was
      impaired by alpha-thrombin. These results demonstrate that thrombin regulates the
      expression of the inducible nitric oxide synthase at a transcriptional level via
      the proteolytic activation of the thrombin receptor in vascular smooth muscle
      cells.

PMID- 8571334
TI  - Comparison of six commercial plasma references for factor VIII, factor IX and von
      Willebrand factor. On behalf of the Subcommittee for Factor VIII and IX of the
      Scientific and Standardization Committee of the ISTH.
AB  - Six brands of normal reference plasma produced in the United States, with
      assigned assay values for factor VII and IX and, in four instances, ristocetin
      cofactor and van Willebrand antigen, were assayed in nine coagulation
      laboratories in academic institutions in the same country. Differences in mean
      assays of reference plasmas, as a percent of labelled potency, were significant
      and were greater than differences among laboratories. Standard methods of
      assigning potency to commercial reference plasmas are recommended.

PMID- 8571335
TI  - Detection by PCR and HphI restriction analysis of a splice site mutation at the
      5' end of intron 15 of the platelet GPIIb (alpha IIb integrin) gene responsible
      for Glanzmann's thrombasthenia type I in Gypsies originating from the Strasbourg
      area.

PMID- 8571336
TI  - Platelet surface activation markers after DDAVP infusion in healthy subjects.

PMID- 8571337
TI  - Prothrombin complex concentrate contains protein Z and prevents bleeding in a
      patient with protein Z deficiency.

PMID- 8571338
TI  - Influence of plasma platelets on activated protein C resistance assay.

PMID- 8571339
TI  - The modified APC resistance test.

PMID- 8571340
TI  - APC-resistance and Mnl I genotype (Gln 506) of coagulation factor V are rare in
      Japanese population.

PMID- 8571341
TI  - Risk of inhibitor development after intermediate purity coagulation factor
      concentrates: is it truly low?

PMID- 8571342
TI  - ['Structures are only ways to let things happen'. Interview by W Sybesma].

PMID- 8571343
TI  - [Veterinary medicine after 2002].

PMID- 8571344
TI  - [The use of veterinary drugs in aqua-culture].

PMID- 8571345
TI  - [Pioneers: veterinarians from earlier times (13). Claude Bourgelat].

PMID- 8571346
TI  - [Inguinal and scrotal hernias in steers].
AB  - A review of the bovine inguinal and scrotal hernia is given on the basis of two
      cases. One six year old Blonde d'Aquitaine bull had to be euthanised with severe
      muscle damage 13 days after surgical intervention, while the other patient, a
      five year old Meusse Rhine and Yssel bull recovered uneventfully after surgery.
      The literature is reviewed and the incidence, pathogenesis, clinical evaluation
      and surgical techniques are described.

PMID- 8571347
TI  - [Lick granuloma in dogs; an obsession for dogs, owners and veterinarians].

PMID- 8571348
TI  - [Minister van Aartsen visits the Royal Dutch Society for Veterinary Medicine. Udo
      on Aujeszky's disease: 'rid of it in 2 years time, unless....'].

PMID- 8571349
TI  - Chemical mixtures and quantitative risk assessment. Proceedings of a symposium.
      November 7-10, 1994.

PMID- 8571350
TI  - Chemical mixtures: challenge for toxicology and risk assessment.
AB  - It is now well-recognized that human environmental exposures are not to single
      chemicals. Rather, humans are exposed, either concurrently or sequentially, to
      multiple chemicals. Challenges that chemical mixtures pose for risk assessment
      and toxicology are presented. Challenge areas include increasing the peer
      reviewed publication of human studies, improving access to peer-reviewed data and
      examining multiple target organs. Two difficult challenges are development of a
      common, consistent language and the use of appropriate and innovative
      experimental designs and analyses. The challenge of elucidation of mechanism(s)
      offers a rational basis for extrapolation across dose levels, exposure durations
      and exposure routes as well as to other species and to other similar chemicals.
      Of particular importance is focusing effort on those areas of investigation where
      answers have the greatest potential for reducing uncertainty in risk assessments
      for chemical mixtures and on those chemical mixtures and multiple chemical
      exposures that have the greatest potential impact on human health. A particularly
      fruitful area for future investigation is determination of the likelihood of
      nonadditive interactions in humans exposed to multiple chemicals at environmental
      exposure levels.

PMID- 8571351
TI  - Toxicological consequences of multiple chemical interactions: a primer.
AB  - The capacity to understand and successfully predict the toxicological
      consequences of multiple chemical interactions is a critical challenge facing the
      scientific community. This article is designed to provide a broad framework
      introducing the concept of interaction, use of consistent and meaningful
      terminology and a descriptive assessment of toxicological foundations within
      which chemical interactions may be evaluated. The article offers guidance on the
      need to place a high priority on assessing the mechanistic basis of
      'superinteractions', that is, unique interactions far exceeding even those of a
      multiplicative nature. The final section of the article provides a detailed
      perspective on how the extensive and successful experience of the pharmaceutical
      industry in assessing and interpreting any interaction for patients can be useful
      to the issues and concerns of chemical interactions for the field of
      environmental toxicology and risk assessment.

PMID- 8571352
TI  - Current and future risk assessment guidelines, policy, and methods development
      for chemical mixtures.
AB  - Humans are typically exposed to low doses of combinations of chemicals rather
      than to one or two chemicals at a time, yet most of the available toxicity data
      provide information on single chemicals or binary pairs, rather than on whole
      mixtures. The use of existing interactions study data for the quantitative risk
      assessment of chemical mixtures is problematic. These studies generally lack the
      necessary statistical characterizations to be useful in quantitative risk
      assessment procedures. The U.S. EPA developed guidelines for risk assessment for
      chemical mixtures in 1986 and is currently in the process of making revisions.
      Significant advances have been made in both the theoretical development and
      application of procedures such as dose addition, response addition, toxicity
      equivalence factors, comparative potency and interactions data characterizations.
      Details on the current revisions to the guidelines are given, along with
      information on the research efforts that have influenced these revisions or that
      represent future directions in chemical mixtures risk assessment.

PMID- 8571353
TI  - Chemical mixtures released from hazardous waste sites: implications for health
      risk assessment.
AB  - Uncontrolled hazardous waste sites (HWS) and exposure to hazardous substances
      continue to pose complex public health problems. This paper presents an overview
      of chemicals, including chemical mixtures, that have been released into
      environmental media in the vicinity of HWS. We describe how this type of
      information is being used to assess the public health implications of exposures
      to chemical mixtures and to develop an integrated program of applied research to
      more accurately characterize the potential health effects of chemical mixtures. A
      narrative, weight-of-evidence approach, incorporating mechanistic insights on
      chemical interactions is described. The utility of this information in the
      context of risk analysis and public health practice is discussed.

PMID- 8571354
TI  - Isobolographic analysis of interactions: an update on applications and utility.
AB  - Isobolographic analysis provides a fundamental basis for assessing whether
      biological responses induced by mixtures of agents are greater, equal or smaller
      than would have been expected on the basis of the individual activities of the
      component agents and the concept of dose additivity. Limited in its direct
      application to binary mixtures, isobolographic analysis provides a conceptual
      framework and an unambiguous terminology, as well as an algebraic paradigm for
      the analysis of the interaction of ternary and higher order mixtures. A library
      of examples generously illustrated graphically is provided to facilitate the
      understanding of the methodology and serve as a guide for investigators who are
      unfamiliar with the approach. Also discussed are the theoretical derivation of
      the isobologram, the representation of various dosage combinations, the
      derivation of the principle of dose additivity, supra-additivity, infra
      additivity, antagonism, the methods for probit analysis of mixture potency,
      effect addition and the consequences of peak effect coincidence in time or lack
      thereof, and the role of isobolographic analysis in the various aspects of dose
      response surface methodology.

PMID- 8571355
TI  - Relating isobolograms to response surfaces.
AB  - The interaction index, isobologram and the appropriate contour of constant
      response of a dose response surface each offer essentially equivalent information
      regarding departures from additivity in a chemical combination. The benefit of
      relating the interaction index and isobolograms to a contour of a fitted dose
      response surface is that departures from additivity can be related to parameters
      of a statistical model. This permits an assessment of the statistical
      significance of the parameters and conclusions regarding the nature of departures
      from additivity which account for the variability inherent in the experiments
      used to generate the data. Relationships between statistical models and
      experimental designs can be exploited to yield economical designs for studying
      chemical combinations.

PMID- 8571356
TI  - An efficient experimental design for detecting departure from additivity in
      mixtures of many chemicals.
AB  - Berenbaum (J. Theor. Biol. 114 (1985) 413-431) described a procedure for
      detecting and characterizing departure from additivity in a combination of c (c >
      or = 2) chemicals. The attraction of this approach is that it is based on the
      concentration-response relationship of each of the individual components and,
      under the assumption of additivity, it is straight forward to predict the
      response of a given combination. Deviations between the observed and predicted
      responses for the combination are associated with departures from additivity.
      Berenbaum based his conclusions regarding synergism/antagonism on numerical
      differences which do not take into account inherent biological variability. We
      have developed a procedure which incorporates experimental variation is based on
      each individual component's concentration-response relationship, and leads to a
      conclusion regarding the statistical significance of any departure from
      additivity. The procedure is illustrated with an example.

PMID- 8571357
TI  - Upper bound risk estimates for mixtures of carcinogens.
AB  - The excess cancer risk that might result from exposure to a mixture of chemical
      carcinogens usually is estimated with data from experiments conducted on
      individual chemicals. An upper bound on the total excess risk is estimated
      commonly by summing individual upper bound risk estimates. The degree to which
      this approach might overstate the true risk associated with the mixture has not
      been evaluated previously. This paper reports the results of a Monte Carlo
      simulation study on the degree of reduction in conservation that might be
      achieved using alternative methods for calculating mixture upper bounds. An
      unexpected finding is that for chemicals that exhibit strongly linear dose
      response relationships, the summing of multistage-model-based upper bounds on
      excess risk can be anti-conservative, that is, it can provide less than the
      nominal 100(1-alpha)% coverage.

PMID- 8571358
TI  - Biphasic responses in synergistic interactions.
AB  - Synergistic reactions, as exemplified by the methylenedioxyphenyl (benzodioxole)
      insecticide synergists, are one of the more studied interactions between
      toxicants. This group of chemicals includes, in addition to synergists such as
      piperonyl butoxide, carcinogens such as safrole and isosafrole and many compounds
      occurring naturally in foods, such as myristicin and piperine. These compounds
      may function as cytochrome P450 substrates, inhibitors and/or inducers. The
      biphasic curve in cytochrome P450 activities following a single dose is the
      result of an initial inhibitory phase followed by a phase of induction, with an
      eventual return to baseline levels. Both inhibition and induction may be isozyme
      specific and different isozymes may be involved in the two activities of the same
      chemical. Details of these activities are presented and their significance is
      discussed.

PMID- 8571359
TI  - Risk assessment: toxicity from chemical exposure resulting from enhanced
      expression of CYP2E1.
AB  - Humans are continuously exposed to a wide variety of xenobiotics either
      voluntarily or from environmental exposure. Many xenobiotics including
      pesticides, nitrosamines, polycyclic aromatic hydrocarbons and halogenated
      hydrocarbons, require bioactivation by P450 enzymes to elicit toxicity. CYP2E1 is
      considered to be toxicologically important in humans because of its capacity to
      produce intermediates that promote cytotoxicity and/or carcinogenicity from a
      number of xenobiotics. Importantly, CYP2E1 is present constitutively and its
      content can be modulated by a variety of factors including xenobiotics such as
      alcohol. Because hepatic concentrations of CYP2E1 can vary considerably from one
      individual to another, the extent of formation of toxic products also varies.
      Indeed, as hepatic concentrations increase so does the risk of toxicity from
      chemicals activated by this P450 enzyme. Many chemicals modulate CYP2E1
      expression and exposure to one compound may alter the toxicological impact of
      another. Considering that CYP2E1 content is related to toxicity from chemicals,
      identifying subjects with elevated levels may lead to minimizing exposure in high
      risk individuals.

PMID- 8571360
TI  - Benzene: a case study in parent chemical and metabolite interactions.
AB  - Benzene, an important industrial solvent, is also present in unleaded gasoline
      and cigarette smoke. The hematotoxic effects of benzene in humans are well
      documented and include aplastic anemia and pancytopenia, and acute myelogenous
      leukemia. A combination of metabolites (hydroquinone and phenol for example) is
      apparently necessary to duplicate the hematotoxic effect of benzene, perhaps due
      in part to the synergistic effect of phenol on myeloperoxidase-mediated oxidation
      of hydroquinone to the reactive metabolite benzoquinone. Since benzene and its
      hydroxylated metabolites (phenol, hydroquinone and catechol) are substrates for
      the same cytochrome P450 enzymes, competitive interactions among the metabolites
      are possible. In vivo data on metabolite formation by mice exposed to various
      benzene concentrations are consistent with competitive inhibition of phenol
      oxidation by benzene. In vitro studies of the metabolic oxidation of benzene,
      phenol and hydroquinone are consistent with the mechanism of competitive
      interaction among the metabolites. The dosimetry of benzene and its metabolites
      in the target tissue, bone marrow, depends on the balance of activation processes
      such as enzymatic oxidation and deactivation processes such as conjugation and
      excretion. Phenol, the primary benzene metabolite, can undergo both oxidation and
      conjugation. Thus, the potential exists for competition among various enzymes for
      phenol. However, zonal localization of Phase I and Phase II enzymes in various
      regions of the liver acinus regulates this competition. Biologically-based
      dosimetry models that incorporate the important determinants of benzene flux,
      including interactions with other chemicals, will enable prediction of target
      tissue doses of benzene and metabolites at low exposure concentrations relevant
      for humans.

PMID- 8571361
TI  - Modulation of chemical-induced lung and liver toxicity by all-trans-retinol in
      the male Sprague-Dawley rat.
AB  - We have previously shown that retinol pretreatment limits the amount of pulmonary
      injury caused by 1-nitronaphthalene in male Sprague-Dawley rats. The main
      objective of this study was to determine if retinol pretreatment can protect the
      lung from the toxicity of other systemic pneumotoxicants. Furthermore because
      retinol has been shown to alter the hepatotoxicity of several chemicals, a
      secondary objective was to evaluate its effects on the liver injury caused by
      these toxicants. Rats were pretreated with all-trans-retinol (75 mg/kg/day, p.o.)
      for 1 week, and given 2-nitronaphthalene (200 mg/kg, i.p.) or paraquat (25 mg/kg,
      i.p.). At 24 h after 2-nitronaphthalene treatment, pulmonary morphological
      changes associated with the bronchiolar epithelium, as well as a moderate
      pneumonitis were observed. Pretreatment of rats with retinol inhibited the
      majority of 2-nitronaphthalene-induced pulmonary damage including the
      infiltration of inflammatory cells and associated edema. However, these animals
      possessed limited lesions associated with their non-ciliated bronchiolar
      epithelial (Clara) cells. Interestingly, pretreatment with retinol also caused a
      significant potentiation of 2-nitronaphthalene-induced liver damage. The
      potentiated hepatotoxicity consisted of centrilobular hepatocyte necrosis with
      infiltration of inflammatory cells. Gadolinium chloride (GdCl3), an inhibitor of
      Kupffer cell function, significantly decreased the potentiated hepatocellular
      injury. In paraquat-treated rats focal areas of damage to the alveolar
      parenchyma, consisting of inflammatory cell infiltration and alveolar sac
      remodeling, were observed at 48 h. Pretreatment with retinol caused significant
      protection from the pulmonary damaged caused by paraquat. Specifically, there was
      a lack of alveolar parenchymal cell damage and inflammatory cell infiltration in
      these animals. From these experiments, we conclude that retinol pretreatment
      decreases the severity of 2-nitronaphthalene and paraquat-induced pulmonary
      toxicity, apparently by inhibiting the inflammatory responses associated with the
      progression of toxic injury. In the liver, retinol potentiated 2-nitronaphthalene
      induced hepatotoxicity by a mechanism which directly involves Kupffer cells.

PMID- 8571362
TI  - Toxicodynamics of low level toxicant interactions of biological significance:
      inhibition of tissue repair.
AB  - Because of the complexity of studying the toxicological effects of mixtures of
      chemicals, much of the mechanistic information has become available through work
      with binary mixtures of toxic chemicals. Mechanisms derived from studies
      employing chemicals at individually nontoxic doses are more useful than the
      mechanisms of interactive toxicity at high doses from the perspective of
      environmental and public health. Several examples of chemical combinations and
      interactive toxicity at low doses are now available. Chlordecone-potentiated
      halomethane hepatotoxicity, where suppression of cell division and tissue repair
      response permits very high amplification of CCl4 injury culminating in animal
      mortality, is one such model. Phenobarbital-potentiated CCl4 injury does not lead
      to animal mortality in spite of much higher liver injury in comparison to the
      chlordecone+CCl4 model. Much higher stimulation of tissue repair allows the
      animals to survive despite higher liver injury. Similar interactions have been
      reported between alcohols and halomethane toxicants. These and other studies have
      revealed that infliction of toxicant-induced injury is accompanied by a parallel
      but opposing tissue repair stimulation response which allows the animals to
      overcome that injury up to a threshold dose. Beyond this threshold, tissue repair
      response is both diminished and delayed allowing unrestrained progression of
      injury. Large doses of chemicals can be predictably lethal owing to these two
      latter effects on tissue repair. Dose-response paradigms in which tissue repair
      response is measured as a parallel but opposing effect to toxic injury might be
      useful in more precise prediction of the ultimate outcome of toxic injury in risk
      assessment. Autoprotection experiments with CCl4, thioacetamide, 2-butoxyethanol
      and related chemicals as well as heteroprotection against acetaminophen-induced
      lethality with thioacetamide are examples where tissue repair stimulation has
      been shown to rescue the animals from massive and normally lethal liver injury.
      The concept of toxicodynamic interaction between inflicted injury and stimulated
      tissue repair offers mechanistic opportunity to fine-tune other aspects of human
      health risk assessment procedure. Tissue repair mechanisms may also offer a
      mechanistic basis to explain species and strain differences as well as to more
      accurately assess inter-individual differences in human sensitivity to toxic
      chemicals. Because tissue repair is affected by nutritional status, assessment of
      risk from exposure to chemicals without attention to nutritional status may be
      misleading. Finally, the concept of using maximum tolerated doses (MTDs) in long
      term toxicity studies such as cancer bioassays may need to be re-examined. MTDs
      might be predictably expected to maximally stimulate cell division and it is
      known that increased cell division is likely to lead to increased number of
      errors in DNA replication thereby predisposing these animals to cancer. It is
      clear that detailed studies of toxicodynamic interaction between tissue injury
      and stimulated tissue repair are likely to yield significant dividends in fine
      tuning risk assessment.

PMID- 8571363
TI  - Variability in glutathione-dependent detoxication in vivo and its relevance to
      detoxication of chemical mixtures.
AB  - Glutathione (GSH) has multiple functions in detoxication and its depletion has
      been associated with an increased risk of chemical toxicity. Because GSH can be
      depleted by different agents, combinations of compounds in chemical mixtures are
      likely to enhance risk over that seen with individual chemicals. Our studies have
      focussed on factors affecting the status of GSH in humans. In addition, we have
      utilized animals models and cell culture systems to understand the role of GSH in
      protection against chemical injury. Results of these studies show that, while
      large variations in sulfur amino acid content occur in the human diet, these
      variations are not correlated simply with GSH levels in vivo as reflected in the
      blood plasma pool. However, plasma levels of GSH do vary with gender, age, race
      and dietary habits, and these factors could affect the risk of toxicity in
      individuals exposed to chemical mixtures. In animal studies, we found that
      extracellular pools of GSH, including the blood plasma, lung-lining fluid and
      small intestinal lumen can be very important in protection against chemically
      induced injury. These pools can function to detoxify chemicals extracellularly,
      supply GSH and its precursors to cells and protect the extracellular surface of
      the plasma membrane from damage. Finally, endogenous gene-activated mechanisms of
      cell death which produce the characteristic morphology of apoptosis are
      susceptible to thiol-disulfide redox regulation. Perturbations in GSH status
      induced by chemical mixtures could alter this regulation and lower the threshold
      for chemically induced cell death by apoptosis. Thus, in vivo GSH status could be
      an important determinant of toxicity from chemical mixtures and may be useful as
      a biomarker for such risk.

PMID- 8571364
TI  - Physiologically based pharmacokinetic/pharmacodynamic modeling of chemical
      mixtures and possible applications in risk assessment.
AB  - Human exposure to chemicals, be it environmental or occupational, is rarely, if
      ever, limited to a single chemical. Therefore, it is essential that we consider
      multiple chemical effects and interactions in our risk assessment process.
      However, with the almost infinitely large number of chemical mixtures in the
      environment, systematic studies of the toxicology of these chemical mixtures with
      conventional methodologies and approaches are impossible because of the immense
      resources and unrealistically long durations required. Thus, the development of
      predictive and alternative toxicology method is imperative. In order to have a
      reasonable chance to deal with the complex issue of toxicology of chemical
      mixtures, we believe that the following concepts must be considered: (1) the
      exploitation of recent advances in computational technology; (2) the utilization
      of mathematical/statistical modeling; (3) coupling computer modeling with very
      focused, mechanistically based, and short-term toxicology studies. Our approach
      is, therefore, the utilization of physiologically based
      pharmacokinetic/pharmacodynamic (PB-PK/PD) modeling, coupled with very focused,
      model-directed toxicology experiments as well as other statistical/mathematical
      modeling such as isobolographic analysis and response surface methodology. Tissue
      dosimetry at the pharmacokinetic and pharmacodynamic levels is achievable with
      simple and complex, but chemically defined, mixtures. Our long-term goal is to
      formulate innovative risk assessment methodologies for chemical mixtures. In this
      presentation, one of our specific research projects is described: PB-PK/PD
      modeling of toxicologic interactions between Kepone and carbon tetrachloride
      (CCl4) and the coupling of Monte Carlo simulation for the prediction of acute
      toxicity.

PMID- 8571365
TI  - Use of tissue slices in chemical mixture toxicology and interspecies
      investigations.
AB  - Precision-cut tissue slices have proven to be a useful in vitro system for
      biotransformation and toxicity studies. Since tissue slices can be readily
      prepared from a variety of tissues and species, they can easily be used for
      interspecies investigations and comparisons. Furthermore, slices can be readily
      prepared from human tissue, thus comparisons (extrapolation) can be made between
      laboratory animals and humans. Slices can also be used to examine the toxic
      interactions of chemicals in vitro. It is important to use the correct
      experimental design to demonstrate toxic interactions and to assure that the
      tissue slices are properly exposed to the chemicals. Overall, tissue slices offer
      a valid in vitro system for performing species comparisons and chemical-chemical
      interaction studies.

PMID- 8571366
TI  - Biochemical mechanisms contributing to species differences in insecticidal
      toxicity.
AB  - Comparison of published LD50 or LC50 levels for a variety of insecticides in
      several vertebrate species indicate that a wide range of toxicity levels exist,
      and these cannot be easily predicted within either a chemical group or within a
      species. There is a relatively limited data base documenting interactions between
      insecticides and other chemicals, either agricultural or non-agricultural;
      however, the fact that all major insecticide groups perturb nervous system
      function as their primary mechanism of acute toxicity suggests the potential for
      interactions. Studies in our laboratories on a select group of phosphorothionate
      insecticides in rats indicated that brain acetylcholinesterase sensitivity to
      inhibition by the oxons, the active metabolites of the phosphorothionates, does
      not correlate with acute toxicity levels. The activities and properties of
      hepatic cytochrome P450-mediated activation (desulfuration) and detoxication
      (dearylation) of the phosphorothionates as well as of A-esterase-mediated
      hydrolysis of oxons contribute substantially to understanding the acute toxicity
      levels in rats, as does the sensitivity of the protective aliesterases to
      phosphorylation. However, in the channel catfish, the acetylcholinesterase
      sensitivity to oxon inhibition reflects the acute toxicity level of these same
      insecticides, and may be largely responsible for determining the acute toxicity
      level in this species. Thus, metabolism of insecticides appears to be far more
      influential in some species than others in determining the toxicity elicited.

PMID- 8571367
TI  - What can we expect from epidemiologic studies of chemical mixtures?
AB  - Determining the health risks of complex mixtures is equally daunting to
      toxicologists using experimental approaches and to epidemiologists using
      observational approaches. Accurate exposure estimation is essential in
      investigating the health consequences of exposures to chemical mixtures; random
      and non-random errors in exposure estimation typically blunt the sensitivity of
      epidemiologic studies and constrain interpretation of findings. On the other
      hand, epidemiologic data have the implicit strength of directly addressing risks
      of exposures in human populations and, for this reason, the findings of
      epidemiologic research have received prominence in the development of
      regulations. Epidemiologic studies have proved informative about many complex
      mixtures including cigarette smoke, diesel exhaust, and even the human diet,
      perhaps one of the most complex mixtures to which we are exposed. The continued
      interest in studying complex chemical mixtures is emphasized by this and other
      recent meetings directed at the topic. The variety of approaches used by
      epidemiologists in approaching complex mixtures reflects the difficulty of
      exposure estimation. Five general strategies can be identified, each with
      differing underlying assumptions and yielding results with distinct implications
      from biological and public health perspectives. These include treating the
      mixture as though it were a single agent, using a single component as a surrogate
      for the mixture, creating a summary index involving multiple components,
      attempting to estimate independent effects of individual components, and
      characterizing the independent and joint effects of key components of the
      mixture. These approaches have proved successful in establishing the adverse
      effects of a number of complex chemical mixtures including mainstream and
      environmental tobacco smoke and outdoor air pollution. New approaches for
      exposure assessment, including personal monitoring and biomarkers, should
      strengthen future epidemiologic investigations of complex chemical mixtures.

PMID- 8571368
TI  - Interaction of gaseous and particulate pollutants in the respiratory tract:
      mechanisms and modulators.
AB  - Human contact with air pollution usually involves exposure to more than one
      chemical, and biological responses to the inhalation of polluted atmospheres
      likely depend upon the interplay between individual materials. Thus,
      characterizing effects from exposures to mixtures of air pollutants is necessary
      for adequate quantitation of health risks. Exposure to gas/particle mixtures may
      result in respiratory tract responses which are additive, or reflect synergistic
      or antagonistic interactions. The occurrence and type of interaction depends upon
      numerous factors, including the biological endpoint being examined and the
      specific exposure conditions, such as concentration, duration, and the
      physicochemical characteristics of the exposure atmosphere. It is, therefore, not
      always possible to predict solely from the presence of certain pollutants in a
      complex atmosphere exactly whether there will be an interaction and, if so, what
      type it will be. This complicates attempts to relate responses observed in
      laboratory studies of mixtures to those which may occur under ambient patterns of
      exposure, an extrapolation needed for human risk assessment.

PMID- 8571369
TI  - Regional deposition of gases and particles in the lung: implications for
      mixtures.
AB  - Considerations of the health effects of pollutant mixtures usually focus on the
      interactions of biochemically-induced events. For example, the effect of
      metabolic enzyme induction by one pollutant on the subsequent effect of another
      pollutant is often considered. Another important aspect of mixture interactions
      is the modulating effects exposure to one pollutant can have on the dosimetry of
      another pollutant and, indirectly, on the effects of the other pollutant. Dose
      modulating effects may be particularly important when considering effects of
      inhaled mixtures on the lung. In this paper, the specific case of O3-induced
      changes on the human lung and the resulting effects on inhaled particle dose are
      considered as a specific example. Ozone has multiple effects on the lung ranging
      from alterations in pulmonary function to effects on lung defense mechanisms such
      as mucociliary transport of particles, and alveolar macrophage engulfment and
      translocation. To better understand how the O3-induced changes can affect
      particle dosimetry, the basic concepts of particle dosimetry are considered
      first. Then the specific O3-induced effects on the human lung are considered in
      the context of the factors governing inhaled particle dose.

PMID- 8571370
TI  - Interaction of air pollutants and pulmonary allergic responses in experimental
      animals.
AB  - Asthma, which is primarily an allergic type of respiratory disease, has increased
      in the U.S. and Europe by 30% over the last decade. Air pollution may play a role
      in this rise, since during episodes of smog, hospital admissions due to asthma
      increase. Ambient air quality has generally improved since the Clean Air Act was
      implemented in 1971 however, and has led some investigators to suggest that the
      increased risk of asthma is associated with a deterioration of indoor air quality
      through the introduction of closed ventilation systems and constant climate
      control. Thus, although the direct health effects of acute and chronic air
      pollutant exposure are not in dispute, emphasis on the sources and location of
      exposure is changing from outdoors to the home environment and workplace. The few
      experimental studies which have investigated the interaction of air pollutants
      with allergic disease have shown that exposure to O3 or NO2 can increase levels
      of allergen-specific antibody and may augment allergic symptoms. These
      experiments are reviewed along with a study conducted in our laboratory which
      demonstrated the enhancing effect of NO2 exposure on immune responses and
      pulmonary inflammation following sensitization and pulmonary challenge with house
      dust mite allergen (HDM). In this study, rats exposed to 5 ppm NO2 for 3 h after
      each immunization had significantly higher levels of serum IgE and local IgA, IgG
      and IgE antibody than air controls. Lymphocyte activity in the spleen and local
      lymph nodes, and pulmonary inflammatory cells were also increased in NO2-exposed
      rats. The results show that exposure to NO2 enhances immune responsiveness and
      the severity of pulmonary inflammation following antigen challenge. Since
      allergic individuals and most asthmatics also have increased immunity to these
      proteins, the possibility that air pollutant exposure enhances immune responses
      to allergens and thus exacerbates immune-mediated lung disease exists.

PMID- 8571371
TI  - Combined effects of paired solvents on the rat's auditory system.
AB  - A number of volatile organic solvents have been shown to be ototoxic to rats, but
      there is little information regarding how solvents might act in this way when
      encountered in combination. To examine this issue, male Long Evans rats were
      exposed by inhalation to pairs of solvents known to be ototoxic when administered
      individually; those reported on here are trichloroethylene+toluene, mixed
      xylenes+trichloroethylene, xylenes+chlorobenzene, and chlorobenzene+toluene. Rats
      were exposed 8 h/day for 5 consecutive days, using complementary proportions of
      isoeffective concentrations of the solvents alone. Hearing was assessed by
      brainstem-evoked response audiometry. The effects were as predicted by a linear
      dose-addition model, indicating additive rather than synergistic or antagonistic
      interactions at the concentrations studied.

PMID- 8571372
TI  - Hematotoxic interactions: occurrence, mechanisms and predictability.
AB  - The available data on the binary chemical interactions involving hematotoxicants,
      particularly organic chemicals causing a reduction in either the number of
      white/red blood cells or the capacity of hemoglobin to transport oxygen, are
      limited. These observations are limited to investigations in rodents of the
      enhancement or attenuation of the hematotoxicity of benzene, dichloromethane and
      dimethylanilines following prior administration of inducers of CYP 2E1 or co
      administration of substrates for this isoenzyme. The relevance of these data on
      interactions for humans exposed at low concentrations can be assessed only when
      the mechanism of interaction is understood at a quantitative level, and
      incorporated within a physiological modeling framework. The present study
      exemplifies the predictability of the magnitude of binary chemical interactions
      in humans exposed to low concentrations, by developing a physiological model of
      the modulation by toluene of dichloromethane-induced carboxyhemoglobinemia.
      Consistent with the basic biochemical principles, this modeling exercise suggests
      that, with competitive metabolic inhibition mechanism, the threshold for binary
      chemical interactions will follow a downward trend with increasing number of
      substrates or structurally-similar substances in a mixture. The use of this kind
      of mechanistic models, along with data from descriptive chemical interaction
      studies, will form the very basis of mechanistic risk assessment methods for
      complex chemical mixtures.

PMID- 8571373
TI  - Review of the interaction between TCDD and glucocorticoids in embryonic palate.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that
      produces adverse biological effects including developmental toxicity and
      teratogenesis. In the mouse embryo, TCDD induces cleft palate and hydronephrosis.
      The synthetic glucocorticoid, hydrocortisone (HC), induces cleft palate and a
      potent, synergistic interaction has been observed between TCDD and HC in C57BL/6N
      embryonic mice. The morphology and etiology of TCDD- and HC-induced clefts are
      distinctly different with formation of small palatal shelves following HC
      exposure and failure of normally-sized shelves to fuse after TCDD treatment. Each
      exposure also alters expression of several growth factors. When EGF, TGF alpha,
      EGF receptor, and the TGF beta's are considered as a combinatorial, interacting
      set of regulators, TCDD and HC each produce a unique pattern of increased and/or
      decreased expression across the set. The interaction of HC and TCDD results in a
      cleft palate whose etiology most closely resembles that observed after HC
      exposure, i.e. small palatal shelves. HC+TCDD-exposure also produces a pattern of
      growth factor expression which closely resembles that seen after HC. Both TCDD
      and HC act through receptor-mediated mechanisms and each compound has its own
      receptor. The Ah receptor (AhR) binds TCDD and the glucocorticoid receptor (GR)
      binds HC. On gestation day (GD) 14, in the embryonic palate exposed to TCDD, the
      AhR was downregulated and the GR expression increased. Conversely, following HC
      exposure, the GR was downregulated and AhR levels were elevated. HC+TCDD produced
      increased expression of both receptors and this pattern would be predicted to
      produce HC-like clefts as the GR-mediated responses would result in small palatal
      shelves. The observed cross-regulation of the receptors is believed to be
      important in the synergistic interaction between TCDD and HC for the induction of
      cleft palate.

PMID- 8571374
TI  - Immunosuppressive potential of several polycyclic aromatic hydrocarbons (PAHs)
      found at a Superfund site: new model used to evaluate additive interactions
      between benzo[a]pyrene and TCDD.
AB  - Exposure to environmental pollution is rarely limited to a single compound or
      even a single class of compounds. The Superfund site located in Massena, NY, is
      contaminated by both halogenated aromatic hydrocarbons (HAHs) and polycyclic
      aromatic hydrocarbons (PAHs). Since representatives of both HAHs and PAHs are
      capable of binding to the aromatic hydrocarbon receptor (AhR), two well
      documented AhR-mediated effects, immunosuppression and induction of hepatic aryl
      hydrocarbon hydroxylase (AHH) activity, were used to evaluate the individual and
      interactive toxicity of these compounds. Fifteen PAHs were first screened for
      their ability to suppress the antibody response in C57BL/6 (Ah+/+) mice immunized
      12 h after a single oral dose of 0.1, 1, 10, or 100 mg/kg. Acenaphthene,
      anthracene, benzo[g,h,i]perylene, fluoranthene, fluorene, naphthalene,
      phenanthrene, and pyrene had little or no effect. Seven PAHs caused > 50%
      suppression at 100 mg/kg. Listed in order of decreasing potency they were
      benzo[k]fluoranthene, benzo[b]fluoranthene, indeno[1,2,3,c,d]pyrene,
      benzo[a]pyrene, chrysene, dibenzo[a,h]anthracene, and benz[a]anthracene. Chrysene
      and benzo[a]pyrene (B[a]P), were further evaluated to determine the dependence of
      these effects on the Ah phenotype by comparing responses of C57BL/6 and congenic
      B6.D2 (Ah-/-) mouse strains. Chrysene immunosuppression was maximal at 0.1 mg/kg
      and was Ah phenotype-independent whereas chrysene AHH induction was Ah phenotype
      dependent, but a 100-fold less sensitive indicator of exposure. In contrast,
      B[a]P immunosuppression and AHH induction were coincident in B6 mice and Ah
      phenotype-dependent. In the final phase, a new approach was used to evaluate
      toxic interactions. This approach considers the mechanism of action of each
      compound and accounts for the fact that the extent of increase in toxic response
      caused by an incremental change of dose is determined by its position on the dose
      response curve rather than on the absolute amount of dose administered. Thus, the
      immunotoxic effects of combined exposure to B[a]P and the AhR ligand, 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), a representative HAH, were evaluated by
      combining the ED20 of B[a]P with the difference between the ED20 and ED40 of
      TCDD, and vice versa, to produce 40% suppression. The results of the combination
      were consistent with additivity regardless of the composite arrangement or
      phenotype although some antagonism could not be excluded with certainty.

PMID- 8571375
TI  - Use of toxic equivalency factors for risk assessment for dioxins and related
      compounds.
AB  - TCDD is the most toxic member of a class of polyhalogenated aromatic hydrocarbons
      that are structurally related, have a similar mechanism of action, and cause the
      same spectrum of responses. Because of the need to assess the risk from complex
      mixtures of these chemicals, the international community has adopted an interim
      approach that assigns relative potency factors to this family of chemicals, based
      on a comparison with the potency of TCDD. Each chemical that fits the criteria
      for this class is assigned a toxic equivalency factor, TEF, which is some
      fraction of that of TCDD. The total toxic equivalency of a mixture, TEQ, is the
      sum of the weighted potency of each compound in the mixture. Although there may
      be some variability between different responses in the determination of a TEF
      value for a compound, endpoint-specific TEFs are usually very similar. There may
      also be some species differences in TEFs. Again, if pharmacokinetic factors are
      taken into account, they are usually relatively minor. TEFs based on intake
      values may also exhibit some differences when compared to those based on target
      tissue concentrations. Using scientific judgment and a broad data base, interim
      TEF values have been recommended for PCDDs, PCDFs, and dioxin-like PCBs. Using
      such values, the TEF approach has been successful at predicting the toxicity of
      real world mixtures. Ongoing studies from our laboratory have validated the
      approach for synthetic mixtures that approximate congener ratios found in food
      samples. Whether non-additive interactions occur with nondioxin-like compounds
      found in environmentally relevant concentrations remain to be determined.

PMID- 8571376
TI  - Mechanistic linkage between DNA adducts, mutations in oncogenes and tumorigenesis
      of carcinogenic environmental polycyclic aromatic hydrocarbons in strain A/J
      mice.
AB  - Five polycyclic aromatic hydrocarbons (PAHs), benzo[a]pyrene (B[a]P),
      benzo[b]fluoranthene (B[b]F), dibenz[a,h]anthracene (DBA), 5-methylchyrsene
      (5MC), and cyclopenta[cd]pyrene (CPP) were examined for their lung tumorigenic
      activities in strain A/J mice, their ability to form PAH-DNA adducts in lung
      tissues, and their ability to mutate the Ki-ras oncogene in PAH-induced tumors.
      PAHs dissolved in tricapyrlin were administered by single intraperitoneal
      injection to male strain A/J mice (20 mice/dose) at doses up to 200 mg/kg
      depending on the PAH. Animals were sacrificed 8 months later and the lungs
      removed, fixed, and surface adenomas enumerated. DBA produced maximal tumor
      multiplicity at the highest dose, 10 mg/kg, giving 32.2 lung adenomas per mouse.
      At 100 mg/kg, B[a]P, B[b]F, 5MC, and CPP gave 12.8, 5.3, 93.1, and 32.2 lung
      adenomas per mouse, respectively. The dose response data for each PAH was fit to
      y = 0.6 + bx1.6, where y is the observed mean lung adenomas per mouse at dose x
      (in mg/kg), 0.6 is the observed background of lung adenomas per mouse, and b is
      the fitted constant representing the potency of each PAH. Statistical analysis
      indicated that the fit of the data to the equation was extremely high with
      adjusted R2 values > 0.985 and small fit standard errors. Based on this equation,
      the relative potencies of B[b]F, DBA, 5MC, and CPP compared to B[a]P were PAH
      (relative activity): DBA (118); 5MC (8.8); CPP (2.9); B[a]P (1.0); B[b]F (0.43).
      DNA adducts were measured by 32P-postlabeling techniques on DNA from lungs of
      mice treated with these PAHs. Adducts identified by cochromatography with
      standards were: from B[a]P, 7R,8S,9S-trihydroxy-10R-(N2-2'-deoxyguanosyl)
      7,8,9,10-tetrahydro- B[a]P, and two adducts resulting from the metabolic
      activation of 9-hydroxy-B[a]P and trans-7,8-dihydroxy-7,8-dihydro-B[a]P; from
      B[b]F, 5-hydroxy-B[b]F-9,10-diol-11,12-oxide-2'-deoxyguanosine; from DBA, three
      adducts from the metabolic activation of trans,trans-3,4,10,11-tetrahydroxy
      3,4,10,11-tetrahydro-DBA and two anti-DBA-3,4-diol-1,2-oxide-N2-[2'
      deoxyguanosine] adducts; from 5MC, 1R,2S,3S-trihydroxy-4-(N2-2'-deoxyguanosyl)
      1,2,3,4-tetrahydro- 5MC; from CPP, four CPP-3,4-oxide-2'-deoxyguanosine adducts.
      Ki-ras codon 12 mutation analysis of PAH-induced tumors was performed using PCR
      and dideoxy sequencing methods. Mutations from lung tumors from tricaprylin
      treated mice were GGT-->GAT, GGT-->CGT, and GGT-->GTT. DBA produced no mutations
      in Ki-ras codon 12 above spontaneous levels. High proportions (> or = 50%) of GGT
      ->TGT mutations from B[a]P, B[b]F and 5MC induced tumors and GGT-->CGT mutations
      from CPP tumors were observed and were statistically significant compared to
      mutations in tricaprylin control tumors. We conclude from the DNA adduct and Ki
      ras mutation studies that bay region diol-epoxide-2'-deoxyguanosine PAH-DNA
      adducts are associated with the GGT-->TGT mutations, and cyclopenta-ring oxide-2'
      deoxyguanosine adducts associated with the GGT-->CGT mutations.

PMID- 8571377
TI  - Toxicology of chemical mixtures: challenges for today and the future.
AB  - A major challenge for the toxicologist involved in safety evaluation of chemical
      mixtures is to test the hypothesis that as a rule exposure to mixtures of
      chemicals at (low) non-toxic doses of the individual chemicals is of no health
      concern. A series of repeated dose studies in rats with defined mixtures of
      chemicals with the same or different target organs revealed that exposure to a
      combination of chemicals compared with exposure to the individual compounds did
      not constitute an evidently increased hazard, provided each chemical was
      administered at a level similar to, or slightly lower than, its own 'No-Observed
      Adverse-Effect-Level'. The results of subacute oral toxicity studies in rats with
      defined mixtures of nephrotoxicants with similar mode of action underlined the
      applicability of the additivity assumption for a mixture of chemicals with simple
      similar action. Safety evaluation of complex chemical mixtures is a challenge
      that can be tackled as follows: first, identify the (e.g. ten) most risky
      chemicals in the mixture, and, second, assess the hazard and the potential health
      risk of the mixture of the most risky chemicals, using procedures developed for
      defined mixtures. To identify interactions between individual compounds, a most
      promising testing strategy appeared to be a statistical approach using a
      fractional two-level factorial design. A challenge for today and the future is to
      gradually substitute mixture-oriented (real life-oriented) standard setting for
      (unrealistic) single chemical-oriented standard setting.

PMID- 8571378
TI  - Chemical mixtures from a public health perspective: the importance of research
      for informed decision making.
AB  - When considered from a public health perspective, the central question regarding
      chemical mixtures is deceptively simple: Are current approaches to risk
      assessment for chemical mixtures affording effective (adequate) and efficient
      (cost-effective) protection for members of our society? Answering this question
      realistically depends on an understanding of the hierarchical goals of public
      health (i.e. prevention, intervention, treatment) and an accurate evaluation of
      the extent to which these goals are being achieved. To allow decision makers to
      make informed judgments about the health risks of chemical mixtures, adequate
      scientific knowledge and understanding must be available to support risk
      assessment activities, which are an integral part of the regulatory decision
      making process. Designing and implementing relevant research depends on the
      existence of a feedback loop between researchers and regulators, where the
      information needs of regulators influence the nature and direction of research
      and the information and understanding generated by researchers improves the
      scientific basis for public health decisions. A clear, consistent, commonly
      accepted taxonomy for describing important mixture-related phenomena is a key
      factor in creating and maintaining the necessary feedback loop. Ultimately, both
      researchers and regulators share a common goal with regard to chemical mixtures;
      improving the state-of-the-science so that we can make informed decisions about
      protecting public health. A survey of research issues and needs that are crucial
      to attaining this goal is presented.

PMID- 8571379
TI  - Preliminary studies of the toxic effects of non-ionic surfactants derived from
      lysine.
AB  - The toxic effects of new synthetic monodisperse non-ionic long-chain N alpha, N
      epsilon-diacyl lysine polyoxyethylene glycol amide compounds with a structural
      resemblance to natural lecithin phospholipids were studied by the haemolytic
      method and the test of the chorioallantoic membrane of the hen's egg (HET-CAM).
      The following compounds were tested: symmetrical N alpha,N epsilon-diacyl lysine
      homologues (N alpha,N epsilon-dihexanoyl, N alpha,N epsilon-dioctanoyl and N
      alpha,N epsilon-didecanoyl lysine) with one methyl ether polyoxyethylene glycol
      chain of different oxyethylene units (dioxyethylene glycol, tetraoxyethylene
      glycol and hexaoxyethylene glycol) as headgroup; symmetrical N alpha,N epsilon
      diacyl lysine homologues with two methyl ether dioxyethylene glycol chains and
      the asymmetrical N alpha-butanoyl, N epsilon-dodecyl lysine with two hydrophilic
      methyl ether dioxyethylene glycol chains as headgroup. A commercial
      (polydisperse) oleoyl polyoxyethylene glycol diethanolamide with an average of
      eight units of ethylene oxide was used as control. All the synthesized tested
      compounds appeared to be less haemolytic and less irritant than the control. The
      synthesized products were studied with regard to their hydrophobic and
      hydrophilic chains in order to evaluate the influence of their structure on their
      haemolytic and irritative action. The results of this study show that the acyl
      chain distribution of these compounds greatly influence toxic effects: the
      asymmetrical compound N alpha-butanoyl,N epsilon-dodecyl lysine-bis[methyl ether
      diethylene glycol]amide was found to be the most haemolytic and irritating
      compound. Among the symmetrical homologues, the shortest-chain compounds N
      alpha,N epsilon-dihexanoyl lysine methyl ether polyoxyethylene glycol amides
      present the least haemolytic and irritating activity, independently of the number
      and length of the hydrophilic methyl ether polyoxyethylene glycol chains. Taking
      into account their surface activity properties and their less haemolytic and
      irritant action, the compound N alpha,N epsilon-dioctanoyl lysine-bis[methyl
      ether diethylene glycol]amide would be the most suitable for practical purposes.

PMID- 8571380
TI  - Binding of a 3,3', 4,4'-tetrachlorobiphenyl (CB-77) metabolite to fetal
      transthyretin and effects on fetal thyroid hormone levels in mice.
AB  - The present study was conducted in order to study the effect of the PCB congener
      3,3', 4,4'-tetrachlorobiphenyl (CB-77) on fetal thyroxin homeostasis in the
      mouse, and to examine a possible underlying mechanism behind the effect. C57BL
      mice were treated with 14C-labelled or unlabelled CB-77 (1 or 10 mg/kg body wt.)
      on day 13 of gestation, and control animals were treated with corn oil. The
      experiment was terminated at 4 days after exposure. Maternal and fetal plasma and
      livers, and whole fetuses for homogenate preparation, were collected and analysed
      for total radioactivity, in vitro binding of 125I-thyroxin to plasma
      transthyretin (TTR; a thyroxin-transporting protein), and free and total thyroxin
      (FT4, TT4) levels. Maternal plasma, fetal plasma and homogenates were also
      analyzed for presence of CB-77 and metabolites. Results showed a dose-dependent
      uptake of radioactivity in plasma and liver, fetal plasma 14C-levels being about
      five-times higher in 10 mg/kg dosed animals as after 1 mg/kg. Fetal; plasma
      levels of total radioactivity were four- to nine-times above maternal levels and
      corresponded to only one compound, the metabolite 4-OH-3,3', 4',5
      tetrachlorobiphenyl (4-OH-tCB). 4-OH-tCB was the major metabolite also in whole
      fetuses, with only small amounts of the parent compound (approximately 15% of the
      4-OH-tCB) and traces (approximately 6%) of two other metabolites, 2-OH-3,3, 4,4'
      tetrachlorobiphenyl and 5-OH-3,3', 4,4'-tetrachlorobiphenyl. Polyacrylamide gel
      electrophoresis confirmed that the 14C-radioactivity in fetal plasma was bound to
      TTR, and revealed that in vitro binding of 125I-T4 to fetal TTR was reduced to
      50% of control values in treated animals (10 mg/kg body wt.). Fetal plasma FT4
      and TT4 levels were significantly decreased (64 and 55% of control fetuses) after
      10 mg/kg treatment. In conclusion, exposure of pregnant mice to CB-77 results in
      the accumulation of the metabolite 4-OH-tCB in fetal mouse plasma. The metabolite
      binds to TTR and is accompanied by a significant decrease in fetal plasma T4
      levels. A causative correlation between TTR binding and effects on T4 levels is
      suggested.

PMID- 8571381
TI  - HI-6 therapy and the acute phase response in the rat.
AB  - The propensity of therapeutic doses of HI-6 (50 mg/kg) in combination with
      atropine sulphate (17 mg/kg), antidotes used to treat organophosphate poisoning,
      to induce the acute phase response (APR) in the laboratory rat was examined. A
      single intraperitoneal injection of HI-6, either alone or with atropine, caused a
      rapid doubling of the plasma corticosterone concentration. However, this increase
      was short-lived in comparison with corticosterone kinetics during the typical,
      turpentine-induced APR. The elevated glucocorticosteroid concentration did not
      affect acute phase protein (APP) gene transcription or mRNA and protein synthesis
      in the livers of oxime/atropine-treated rats. On the basis of these findings, we
      concluded that the administered doses of HI-6 and atropine did not induce the
      generalised, non-specific APR.

PMID- 8571382
TI  - Effects of ethanol administration on cerebral non-protein sulfhydryl content in
      rats exposed to styrene vapour.
AB  - Glutathione (GSH) and other non-protein sulfhydryls (NPS) are known to protect
      cells from oxidative stress and from potentially toxic electrophiles formed by
      biotransformation of xenobiotics. This study examined the effect of a
      simultaneous administration of styrene and ethanol on NPS content and lipid
      peroxidation in rat liver and brain. Hepatic cytochrome P450 and cytochrome b5
      content, aniline hydroxylase and aminopyrine N-demethylase activities as well as
      the two major urinary metabolites of styrene, mandelic and phenylglyoxylic acids
      were also measured. Groups of rats given ethanol for 3 weeks in a liquid diet
      were exposed, starting from the second week, to 326 ppm of styrene (6 h daily, 5
      days a week, for 2 weeks). In control pair-fed animals, styrene produced about
      30% depletion of brain NPS and 50% depletion of hepatic NPS. Subchronic ethanol
      treatment did not affect hepatic NPS levels, but caused 23% depletion of brain
      NPS. Concomitant administration of ethanol and styrene caused a NPS depletion in
      brain tissue in the order of 60%. These results suggest that in the rat,
      simultaneous exposure to ethanol and styrene may lead to considerable depletion
      of brain NPS. This effect is seen when both compounds are given on a subchronic
      basis, a situation which better resembles possible human exposure.

PMID- 8571383
TI  - Biliary excretion of biochemically active cyanobacteria (blue-green algae)
      hepatotoxins in fish.
AB  - Previous reports demonstrated that microcystin and related cyanobacteria
      polypeptides are rapidly cleared from plasma and accumulate in liver tissue. In
      the present study, we have used their ability to inhibit protein phosphatases to
      show that these cyanobacteria hepatotoxins are excreted into the bile of
      experimentally poisoned rainbow trout. At various times after oral administration
      of hepatotoxic Microcystis aeruginosa, bile samples were analysed for microcystin
      content by methanol extraction and protein phosphatase assays. An inhibitory
      principle that specifically suppressed protein phosphatase activity was detected
      in all bile samples removed between 1 and 72 h after oral exposure to toxic
      algae. These results indicate that biochemically active microcystin molecules are
      excreted into the biliary tract of poisoned fish.

PMID- 8571384
TI  - Effect of pyrethroids on pentobarbital-induced sleeping time in relation to the
      chemical structure.
AB  - The effect of pyrethroids on pentobarbital-induced sleeping time was examined in
      mice. Pentobarbital-induced sleeping time was defined as the time interval from
      loss of righting reflex to reappearance of righting reflex. Mice were
      administered pyrethroids orally 2 h before the intraperitoneal injection of
      pentobarbital at a dose of 45 mg/kg. Pyrethroids with a cyano group on the
      alcohol moiety, such as cyphenothrin, cypermethrin, fenvalerate and fenpropathrin
      shortened the pentobarbital-induced sleeping time, while pyrethroids with an
      ethynyl group on the acid moiety, such as prallethrin, furamethrin and
      empenthrin, prolonged sleeping time. Pyrethroids with neither a cyano nor an
      ethynyl group had no effect on sleeping time. We, thus, found a clear
      relationship between the chemical structure of pyrethroids and their effect on
      pentobarbital-induced sleeping time.

PMID- 8571385
TI  - Comparative evaluation of amiodarone-induced phospholipidosis and drug
      accumulation in Fischer-344 and Sprague-Dawley rats.
AB  - Amiodarone (AD) and its major metabolite, desethylamiodarone (desethylAD), are
      both phospholipogenic. The present study was undertaken to evaluate the
      comparative susceptibilities of male Fischer-344 and Sprague-Dawley rats to AD
      induced phospholipidosis in alveolar macrophages (AMs), liver and kidney tissue
      and the concomitant accumulation of AD and desethylAD in these cells, tissues and
      plasma. Rats were administered AD (100 mg/kg/day, p.o.) for 1 week. Plasma
      concentrations of AD and desethylAD were approximately 4- and 12-fold higher,
      respectively, in Fischer-344s compared to Sprague-Dawleys 24 h after the last
      dose. AD and desethylAD levels in AMs were approximately 12- and 25-fold higher,
      respectively, in Fischer-344s than Sprague-Dawleys. In the liver and kidney,
      levels of both compounds were also significantly higher in Fischer-344s than
      Sprague-Dawleys. Ultrastructural features indicative of phospholipidosis were not
      observed consistently in any tissue except AMs from treated Fischer-344s. AM
      total phospholipid increased nearly 5-fold in Fischer-344s, while Sprague-Dawleys
      showed no increase over control. AMs from both strains incubated with 10 microM
      AD or desethylAD in vitro were not significantly different in their accumulation
      of the compounds. When incubated with AD or desethylAD, the lysosomal
      phospholipases A1 partially purified from AMs of both strains were equally
      sensitive to inhibition as measured by the drug concentration giving 50%
      inhibition in activity (IC50). The results of this study indicate that at the
      same administered dose, AD and desethylAD, accumulate to higher tissue levels and
      are more phospholipogenic in male Fischer-344 rats than in male Sprague-Dawley
      rats. The basis for the high susceptibility of Fischer-344 rats to AM-induced
      phospholipidosis is unknown at present but appears not to be related to
      biochemical or cellular features of the AMs.

PMID- 8571386
TI  - Alpha 2u-globulins in the urine of male rats: a reliable indicator for alpha 2u
      globulin accumulation in the kidney.
AB  - Increases in kidney-type-alpha 2u-globulin (alpha G-K, molecular weight
      approximately 16 kDa) were detected in the urine of male adult rats treated with
      d-limonene by immunoblotting analysis using an antiserum which distinguishes
      native-type-alpha 2u-globulin (alpha G-N, molecular weight approximately 19 kDa)
      from alpha G-K. When male adult rats received d-limonene by gavage (0-300
      mg/kg/day) for 14 consecutive days, dose-dependent increases in urinary excretion
      of alpha G-K were observed at a dosage level of more than 30 mg/kg/day. This was
      found to be directly correlated with alterations in the concentration of renal
      alpha G-K as well as the accumulation of hyaline droplets in proximal convoluted
      tubule (PCT) epithelial cells in the kidneys. Marked elevation of urinary alpha G
      K was also noted following oral treatment of adult male rats with 2,2,4
      trimethylpentane (TMP), 1,4-dichlorobenzene (DCB), decalin and isophorone (ISP)
      by gavage (1.5 mmol/kg/day) for 7 consecutive days, again in association with
      increased concentrations of renal alpha G-K and hyaline droplet accumulation in
      renal PCT epithelial cells. However, no such increases in urinary alpha G-K were
      observed for male adult rats treated with nephrotoxic chemicals such as puromycin
      aminonucleoside (PAN) (15 mg/kg/day, s.c., 14 consecutive days) or hexachloro-1,3
      butadiene (HCBD) (100 mg/kg/day, p.o., 5 consecutive days), lacking the ability
      to cause kidney accumulation of the hyaline droplets and alpha G-K. The findings
      in this study thus indicate that measurement of urinary alpha G-K can give a
      reliable estimates not only of the potential to cause renal accumulation of alpha
      2u-globulin but also of its magnitude.

PMID- 8571387
TI  - Prevention of cisplatin nephrotoxicity by exogenous atrial natriuretic peptide.
AB  - The ability of atrial natriuretic peptide (ANP) to prevent cisplatin-induced
      nephrotoxicity was compared to the protective effect of 3% NaCl. ANP (1
      microgram/kg/min), 3% NaCl or peptide buffer vehicle (50 microliters/min) were
      infused for 45 min to conscious unrestrained rats immediately after cisplatin
      administration (5 mg/kg i.v.). Measurements taken 72 h after drug treatment
      indicated that compared to animals receiving cisplatin only, ANP co-treated rats
      had lower post-treatment plasma creatinine concentrations (0.70 +/- 0.07 vs 1.3
      +/- 0.17 mg/dl; P < 0.05), blood urea nitrogen (BUN) concentrations (44.2 +/- 5.8
      vs. 65.5 +/- 2.1 mg/dl; P < 0.05) and higher post-treatment glomerular filtration
      rates (GFR) (0.71 +/- 0.18 vs. 0.14 +/- 0.03 ml/min; P < 0.05). ANP was as
      effective as 3% NaCl in preventing cisplatin nephrotoxicity in this model. The
      effect of ANP co-treatment on the anti-tumor activity of cisplatin was also
      examined using the Walker 256 carcinosarcoma model. ANP treatment did not result
      in any observable loss in anti-tumor activity. When ANP was administered 72 h
      after cisplatin treatment, improvement in GFR was observed for the duration of
      the infusion, confirming the beneficial effect of ANP on cisplatin-damaged
      kidneys. ANP may have a role in the treatment and prevention of cisplatin
      nephrotoxicity especially in clinical situations where treatment with a large
      fluid volume is contraindicated.

PMID- 8571388
TI  - Citrinin produces acute adverse changes in renal function and ultrastructure in
      pentobarbital-anesthetized dogs without concomitant reductions in
      [potassium]plasma.
AB  - Citrinin's nephrotoxicity was examined in pentobarbital-anesthetized dogs under
      conditions that minimized or avoided significant changes in a number of its
      actions that could indirectly and adversely affect renal function and
      ultrastructure, such as, (i) major acute reductions in blood pressure and renal
      blood flow and, (ii) emesis and diarrhea that could lead to dehydration and
      electrolyte imbalances, especially hypokalemia. Slow intravenous injection of 20
      mumol citrinin/kg to pentobarbital-anesthetized dogs did not induce any
      alterations in renal tissue ultrastructure or in any of the 23 whole blood,
      plasma or renal function parameters that were monitored over a 6-h post-citrinin
      period. On the other hand, 80 mumol citrinin/kg produced significant increases in
      the hematocrit and in the renal excretion rates of protein and glucose; modest
      reductions were noted in CIN, RBF and excretion rate of inorganic phosphorus. In
      addition, 80 mumol citrinin/kg induced ultrastructural lesions in the cells of
      the S2 proximal tubular segment, the thick ascending limb, the distal convoluted
      tubule and the collecting ducts. The glomeruli, S1 and S3 cells of the proximal
      tubule and the thin descending and ascending limbs of Henle's loop were
      unaffected by both citrinin doses. The location and nature of the adverse
      ultrastructural lesions were most likely the result of the direct actions of
      citrinin (or a citrinin metabolite) since the effects of citrinin that could lead
      to indirect adverse renal effects were totally avoided or greatly minimized.

PMID- 8571389
TI  - Effects of cadmium on the release of tissue plasminogen activator and plasminogen
      activator inhibitor type 1 from cultured human vascular smooth muscle cells and
      fibroblasts.
AB  - To evaluate the toxicity of cadmium on the blood fibrinolytic system during
      hemostasis, human vascular smooth muscle cells and human fibroblasts were
      cultured in the presence of cadmium chloride. It was found that cadmium markedly
      decreased the release of both tissue plasminogen activator antigen (t-PA:Ag) and
      plasminogen activator inhibitor type-1 antigen (PAI-1:Ag) from vascular smooth
      muscle cells. Other heavy metals including lead, manganese, mercury and nickel
      also decreased the t-PA:Ag and PAI-1:Ag release, however, cadmium was the most
      potent inhibitor. On the other hand, the release of t-PA:Ag was significantly
      increased whereas that of PAI-1:Ag was unaffected in fibroblasts after exposure
      to cadmium. Of the tested heavy metals, only cadmium increased the t-PA:Ag
      release from the cells. Electrophoretic enzymography revealed that cadmium
      reduced the activity of plasminogen activators in the conditioned medium of both
      vascular smooth muscle cells and fibroblasts. Cadmium markedly decreased the
      incorporation of [3H]leucine accompanied with a significant increase in the
      leakage of lactate dehydrogenase in vascular smooth muscle cells; however, the
      metal did not change these markers in fibroblasts. These results suggest that the
      regulation of fibrinolysis mediated by vascular smooth muscle cells and
      fibroblasts during hemostasis may be disturbed by cadmium.

PMID- 8571390
TI  - Benzoyl peroxide cytotoxicity evaluated in vitro with the human keratinocyte cell
      line, RHEK-1.
AB  - The human keratinocyte cell line, RHEK-1, was used to evaluate the cytotoxicity
      of benzoyl peroxide (BZP). As determined with the neutral red (NR) cytotoxicity
      assay, the 24-h midpoint (NR50) toxicity values, in mM, were 0.11 for BZP and
      29.5 for benzoic acid, the stable metabolite of BZP. Irreversible cytotoxicity
      occurred after a 1-h exposure to 0.15 mM BZP and greater. When exposed to BZP for
      7 days, a lag in growth kinetics was first observed at 0.06 mM BZP. Damage to the
      integrity of the plasma membrane was evident, as leakage of lactic acid
      dehydrogenase occurred during a 4-h exposure to BZP at 0.05 mM and greater.
      Intracellular membranes were also affected, as extensive vacuolization, initially
      perinuclear but then spreading throughout the cytoplasm, was noted in BZP
      stressed cells. The generation of reactive free radicals from BZP was suggested
      by the following: the intracellular content of glutathione was lowered in cells
      exposed to BZP; cells pretreated with the glutathione-depleting agent,
      chlorodinitrobenzene, were hypersensitive to a subsequent challenge with BZP;
      lipid peroxidation by BZP was inducible in the presence of Fe2+; and cells
      previously maintained in a medium amended with vitamin E, an antioxidant, were
      more resistant to BZP, showed less lipid peroxidation in the presence of BZP+Fe2+
      and did not develop the extensive intracellular vacuolization as compared to non
      vitamin E maintained cells.

PMID- 8571391
TI  - Bifonazole, but not the structurally-related clotrimazole, induces both
      peroxisome proliferation and members of the cytochrome P4504A sub-family in rat
      liver.
AB  - Male Wistar rats were treated with a low (150 mumol/kg) and a high (750 mumol/kg)
      dose of either clotrimazole of bifonazole. Bifonazole, but not clotrimazole,
      exhibited the characteristics of a peroxisome proliferator including hepatomegaly
      (increase in liver:body weight ratio), up to a 4-fold induction of lauric acid
      omega-hydroxylase activity and an 8-fold induction of palmitoyl-CoA oxidation by
      rat liver peroxisomes. This induction of enzyme activities was paralleled by
      increased protein levels as determined by immunochemical analysis for both liver
      microsomal cytochrome P4504A1 and the peroxisomal trifunctional protein of the
      beta-oxidation spiral. In contrast, clotrimazole did not increase protein levels
      of either cytochrome P4504A or the trifunctional protein. Western blot analyses
      demonstrated that bifonazole also induced P4502B1/2B2, P4503A and P4501A1, but
      not P4502E1. Clotrimazole induced a similar spectrum of P450s as determined by
      Western blotting with the exception that this azole was a marginal P4501A1
      inducer under the conditions studied. Taken collectively, our data provides
      evidence that bifonazole is one of the increasingly recognised, non-carboxylate
      containing xenobiotics that induce both peroxisome proliferation and the
      cytochrome P4504A sub-family in rat liver.

PMID- 8571392
TI  - Serum amino acid changes in rats with thioacetamide-induced liver cirrhosis.
AB  - To date, no attempt has been made to study alterations occurring in the amino
      acid profile in chronic models of thioacetamide-induced liver cirrhosis. In this
      work, changes in serum amino acids and proteins in rats with thioacetamide
      induced liver cirrhosis are reported, together with changes in enzyme activities
      in the liver and serum. Seventeen female Wistar rats were used. Eight rats were
      given 300 mg thioacetamide/l in drinking water for 4 months and nine rats were
      given water ad libitum during the same time-period. Significant increases in
      glycine, alanine, serine, methionine, glutamate, ornithine, phenylalanine,
      tyrosine, histidine and proline were observed in rats with the resulting
      experimental liver cirrhosis. Threonine, taurine, glutamine, lysine and
      citrulline tended to increase while isoleucine, leucine, aspartate, arginine and
      tryptophan tended to decrease. Total and nonessential amino acids increased
      significantly in cirrhotic animals. Total essential and aromatic amino acids
      tended to increase in the thioacetamide-treated group, whereas branched chain
      amino acids tended to decrease in the same group. Regarding serum proteins, a
      decrease in albumin concentration in the thioacetamide-treated animals was the
      only change detected. The liver enzyme activities under observation (aspartate
      and alanine aminotransferases, glutamate dehydrogenase and threonine deaminase)
      were lower in the thioacetamide group. Decreases were significant for both
      transaminases and threonine deaminase. Results for serum activities showed that
      transaminases did not change in thioacetamide-treated rats in comparison with
      controls. In contrast, alkaline phosphatase rose dramatically in cirrhotic rats.
      We conclude that the serum amino acid pattern in this chronic model of liver
      cirrhosis resembles in part that of the corresponding human disease.

PMID- 8571393
TI  - Human cytochromes P450 expressed in Escherichia coli: production of specific
      antibodies.
AB  - Cytochromes P450 (CYP) constitute a superfamily of enzymes involved in the
      metabolism of xenobiotics. Within the same subfamily, the isoforms present strong
      similarities, making them difficult to characterize and differentiate. Using
      heterologous expression in bacteria, five pure human CYP (1A1, 1A2, 2C9, 2E1,
      3A4) were easily obtained and used as antigens to raise specific antibodies.
      These antibodies were characterized for their specificity and sensitivity by
      immunoblots; anti-CYP3A4 was immunoinhibitor. These antibodies could be used in
      association with other means to identify the CYPs responsible for production of a
      given metabolite. The use of our human recombinant CYP1A2 as antigen and the
      corresponding specific antibody enabled us to quantify the CYP1A2 content in 43
      human livers. The average level was 69 pmol of CYP1A2/mg of microsomal proteins.
      Finally, these antibodies were also used to evaluate the level of heme
      incorporation in human microsomal CYP expressed in yeasts.

PMID- 8571395
TI  - Renal amino acid transport in immature and adult rats during thallium-induced
      nephrotoxicity.
AB  - The effect of Tl2SO4 (Tl, 2 mg/100 g b.wt.) on renal amino acid excretion and
      plasma amino acid composition was investigated in 10- and 55-day-old rats. Tl
      decreased glomerular filtration rate only in adult rats. On the other hand, the
      renal fractional excretion (FE) of amino acids was distinctly higher in adult
      rats as a sign of lower amino acid reabsorption capacity after Tl. In immature
      animals FE was increased only for a few amino acids. However, in both age groups
      Tl administration significantly decreased plasma amino acid concentrations, and
      was more pronounced in immature rats. The investigation of renal amino acid
      handling (1) confirms that Tl was more nephrotoxic in 55-day-old animals as
      demonstrated before using other parameters for nephrotoxicity testing and (2)
      showed that determination of renal amino acid handling is a suitable marker for
      nephrotoxicity in adult rats.

PMID- 8571394
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on humoral and cell-mediated
      immunity in Sprague-Dawley rats.
AB  - There is much discussion about the occurrence of 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD)-induced effects on the human immune system. Extensive studies have
      been conducted in mice, but those results cannot explain some of the
      epidemiological data obtained in exposed humans. Therefore, studies in other
      laboratory animal species are needed. The aim of these experiments was to examine
      effects of TCDD on cell- and humoral-mediated immunity in male Sprague-Dawley
      (SD) rats. A delayed-type hypersensitivity (DTH) assay was used to examine cell
      mediated immunity. A time-course study demonstrated that TCDD treatment on day -5
      relative to immunization (day 0) produced the greatest effect on cell-mediated
      immunity. In a dose-response experiment, rats were treated with 1, 3, 10, 20, 30,
      40 and 90 micrograms TCDD/kg The effect of TCDD on cell-mediated immunity
      displayed an inverted U-shaped dose-response curve, in that low doses enhanced
      and high doses suppressed this immune function. This is the first study to
      demonstrate an U-shaped dose-response curve of TCDD on the immune system. Primary
      antibody response to sheep red blood cells (SRBC) was used as endpoint to study
      the effect of TCDD on humoral immunity. Serum anti-SRBC IgM and IgG levels were
      measured using an enzyme-linked immunosorbent assay (ELISA). In the dose range
      examined (10, 20 and 40 micrograms TCDD/kg), serum IgM levels were not affected
      by TCDD compared to controls at 7 and 14 days after immunization. In contrast,
      serum IgG levels were dose-dependently elevated both 7 and 14 days after
      immunization, with a maximum increase of 59% over controls.

PMID- 8571396
TI  - Stimulation by oxazolone of increased IL-6, but not IL-10, in the skin of mice.
AB  - Interleukin 6 (IL-6), a multi-functional cytokine, is expressed constitutively by
      epidermal Langerhans cells and can be produced also by keratinocytes following
      stimulation. We have investigated the production of cutaneous IL-6 following
      topical exposure of mice to oxazolone, a potent contact allergen. Homogenates of
      ear skin prepared from untreated BALB/c strain mice, or from mice exposed on the
      dorsum of both ears to vehicle alone, contained low levels of IL-6. Topical
      application of oxazolone to the ears of mice induced a rapid and dose-dependent
      increase in IL-6 expression that was maximal 4-8 h following application and
      remained elevated for up to 24 h. Under the same conditions of exposure the
      expression of a second epidermal cytokine, interleukin 10, a product of
      keratinocytes, was unaffected. It is concluded that topical exposure to the
      chemical allergen oxazolone results in the selective stimulation of cutaneous
      cytokine production. The experimental approach described herein provides a simple
      and reliable method for the investigation of induced changes in the expression of
      skin cytokines.

PMID- 8571397
TI  - Risk-based concentrations: prioritizing environmental problems using limited
      data.
AB  - A difficult task faced by regulatory agencies is that of choosing, on the basis
      of limited data, which environmental problems to address. This paper incorporates
      USEPA risk assessment methods into a quantitative approach for prioritizing
      locations, contaminants and media according to potential health risk. USEPA has
      developed either a reference dose (a chronic dose without adverse effect) or
      slope factor (upper bound lifetime cancer risk per mg.kg-1.d-1) for many
      substances. This work combines these 'toxicological constants' with predetermined
      risk levels (either a 10(-6) cancer risk or a chronic intake equal to the
      reference dose) and protective human exposure assumptions (e.g. 70-kg body mass,
      30-year exposure, 2-1.d-1 drinking water ingestion, etc.) to produce risk-based
      concentrations for 596 contaminants in air, drinking water, edible fish and soil.
      Because USEPA designed its methods to estimate upper bound risks, these risk
      based concentrations are likely to be protective of human health. Regulatory
      officials can use this information to calculate numerical ratios between measured
      environmental levels and risk-based concentrations. These ratios serve as a
      surrogate for potential health impacts and can be used to prioritize problems for
      attention. Ratio calculation and ranking can be automated for searches of
      computerized environmental databases.

PMID- 8571398
TI  - Computer prediction of possible toxic action from chemical structure: an update
      on the DEREK system.
AB  - Computer-based assessment of potential toxicity has become increasingly popular
      in recent years. The knowledge-base system DEREK is developed under the guidance
      of a multinational Collaborative Group of expert toxicologists and provides a
      qualitative approach to toxicity prediction. Major developments of the DEREK
      program and knowledge-base have taken place in the last 3 years. Program
      developments include improvements in both the user interface and data processing.
      Work on the knowledge-base has concentrated on the areas of genotoxicity and skin
      sensitisation. DEREK's predictive capabilities for these toxicological end-points
      has been demonstrated. In addition to the continued expansion of the knowledge
      base, a number of enhancements are planned in the DEREK program. In particular,
      work is in progress to develop further DEREK's ability to report the reasoning
      behind its predictions.

PMID- 8571399
TI  - Vanadium(IV)-mediated free radical generation and related 2'-deoxyguanosine
      hydroxylation and DNA damage.
AB  - Free radical generation, 2'-deoxyguanosine (dG) hydroxylation and DNA damage by
      vanadium(IV) reactions were investigated. Vanadium(IV) caused molecular oxygen
      dependent dG hydroxylation to form 8-hydroxyl-2'-deoxyguanosine (8-OHdG). During
      a 15 min incubation of 1.0 mM dG and 1.0 mM VOSO4 in phosphate buffer solution
      (pH 7.4) at room temperature under ambient air, dG was converted to 8-OHdG with a
      yield of about 0.31%. Catalase and formate inhibited the 8-OHdG formation while
      superoxide dismutase enhanced it. Metal ion chelators, DTPA and deferoxamine,
      blocked the 8-OHdG formation. Incubation of vanadium(IV) with dG in argon did not
      generate any significant amount of 8-OHdG, indicating the role of molecular
      oxygen in the mechanism of vanadium(IV)-induced dG hydroxylation. Vanadium(IV)
      also caused molecular oxygen-dependent DNA strand breaks in a pattern similar to
      that observed for dG hydroxylation. ESR spin trapping measurements demonstrated
      that the reaction of vanadium(IV) with H2O2 generated OH radicals, which were
      inhibited by DTPA and deferoxamine. Incubation of vanadium(IV) with dG or with
      DNA in the presence of H2O2 resulted in an enhanced 8-OHdG formation and
      substantial DNA double strand breaks. Sodium formate inhibited 8-OHdG formation
      while DTPA had no significant effect. Deferoxamine enhanced the 8-OHdG generation
      by 2.5-fold. ESR and UV measurements provided evidence for the complex formation
      between vanadium(IV) and deferoxamine. UV-visible measurements indicate that dG,
      vanadium(IV) and deferoxamine are able to form a complex, thereby, facilitating
      site-specific 8-OHdG formation. Reaction of vanadium(IV) with t-butyl
      hydroperoxide generated hydroperoxide-derived free radicals, which caused 8-OHdG
      formation from dG and DNA strand breaks. DTPA and deferoxamine attenuated
      vanadium(IV)/t-butyl-OOH-induced DNA strand breaks.

PMID- 8571400
TI  - Hydroperoxide-induced nucleotide degradation and adenosine formation in isolated
      rat cardiomyocytes.
AB  - The effect of tert-butyl hydroperoxide (tBH) on the nucleotide level in isolated
      cardiomyocytes from adult rats was examined. Incubation of myocytes with the
      hydroperoxide resulted in loss of both ATP and NAD from mitochondria and cytosol.
      In contrast, only the cytosolic level of NADP was increased. The effect on
      myocyte content of ADP and AMP was less pronounced. A significant increase in
      formation and release of adenosine also occurred in tBH-exposed cells. Treatment
      of cardiomyocytes with tBH resulted in a progressive decline of rod-shaped and
      viable cells, which was accompanied by an increase in numbers of hypercontracted
      and round myocytes in the incubation mixture. Electron microscopic examination
      showed an intense contraction of the cells. In summary our results demonstrate
      that plasma membrane damage and hypercontraction are early manifestations of tBH
      induced injury to isolated cardiomyocytes. The depletion of ATP and formation of
      adenosine also suggest that degradation of adenine nucleotides may contribute to
      the cytotoxicity caused by tBH. Possible mechanisms involved in the ATP depletion
      are discussed.

PMID- 8571401
TI  - Glutathionyl hydroquinone: a potent pro-oxidant and a possible toxic metabolite
      of benzene.
AB  - Iron catalysed bleomycin (an antitumor antibiotic)-dependent degradation of DNA
      was investigated in the presence of glutathionyl hydroquinone (GHQ). DNA
      degradation was enhanced twelve-fold in the presence of iron and GHQ and three
      fold in the presence of iron and glutathione (GSH) as compared to iron alone. The
      degradation of DNA was linear with the increase in concentration of GHQ or GSH
      keeping the iron, bleomycin and other factors constant. The presence of
      oxyradical scavengers, viz., thiourea, mannitol, albumin, superoxide dismutase,
      catalase and dimethyl sulfoxide caused significant inhibition of degradation of
      DNA by GHQ and iron. All the externally added GHQ to bone marrow cell lysate was
      completely demonstrable by the assay of iron-catalyzed bleomycin-dependent
      degradation of DNA. Superoxide radical generation was demonstrable during the
      incubation of GHQ. Thus, the present study revealed that GHQ is a potent pro
      oxidant and this observation is significant in understanding the mechanism of
      benzene toxicity with the possibility of GHQ as one of the toxic metabolites of
      benzene.

PMID- 8571402
TI  - Protection against cadmium-metallothionein nephrotoxicity in streptozotocin
      induced diabetic rats: role of increased metallothionein synthesis induced by
      streptozotocin.
AB  - Protection against the development of nephrotoxicity following the administration
      of cadmium-metallothionein (CdMT) at a dose of 0.4 mg Cd per kg body weights was
      studied in streptozotocin (STZ)-induced diabetic rats. Six groups of Wistar male
      rats were used (Groups A and B, Groups A1 and C, and Groups A2 and D were
      injected intraperitoneally with STZ at doses of 0, 50 and 100 mg/kg,
      respectively, and then 6 days later, Groups B, C and D were injected
      subcutaneously with CdMT). Proteinuria, albuminuria and transferrinuria were
      observed after the administration of CdMT, and a dose-related decrease following
      the increased STZ dose was seen in Groups B, C and D. The concentrations of
      metallothionein (MT) and zinc (Zn) in liver and kidney were dose-dependently
      increased in Groups B, C and D. Induction of increased MT synthesis in liver and
      kidney as the result of the STZ treatment was observed in this study. In
      particular, a remarkable increase in liver MT concentration was induced by STZ,
      and transport to the kidney of MT synthesized in liver may perhaps explain the
      protection against cadmium nephrotoxicity in STZ-induced diabetic rats.

PMID- 8571403
TI  - Induction of dedifferentiated clones of LLC-PK1 cells upon long-term exposure to
      dichlorovinylcysteine.
AB  - Dichlorovinylcysteine (DCVC), the key metabolite of the nephrotoxic and
      nephrocarcinogenic chemicals, trichloroethylene and dichloroacetylene, exerts
      potent acute cellular toxicity in LLC-PK1 cells (Vamvakas S., Bittner, D.,
      Dekant, W. and Anders, M.W. (1992). Events that precede and that follow S-(1,2
      dichlorovinyl)-L-cysteine-induced release of mitochondrial Ca2+ and their
      association with cytotoxicity to renal cells. Biochem. Pharmacol. 44, 1131-1138).
      In the present study we investigated whether long-term exposure of LLC-PK1 cells
      to low, non-cytotoxic concentrations of DCVC results in stable morphological and
      biochemical dedifferentiation. After 7 weeks exposure to 1 and 5 microM DCVC,
      morphologically changed single cells were picked under the microscope and
      cultured in absence of DCVC for 4-8 weeks. In contrast to the physiological
      cuboidal shape of untreated LLC-PK1 cells, the clones derived from long-term
      exposure to DCVC consisted of elongated, spindle-shaped cells tending to form
      irregular borders. Moreover, glucose uptake, pH-dependent ammonia production and
      dome formation, important indicators of the renal tubule origin of the LLC-PK1
      cells, were severely impaired in the clones. In addition to the loss of membrane
      polarity, the clones exhibited altered composition of the nuclear matrix and
      intermediate filament proteins by two-dimensional gel electrophoresis, increased
      poly(ADP-ribosyl)ation of nuclear proteins and enhanced expression of c-fos. The
      induction of dedifferentiated LLC-PK1 clones with stable characteristics upon
      long-term exposure to the nephrocarcinogen DCVC may represent a useful in vitro
      model to study biochemical alterations involved in chronic renal toxicity and
      carcinogenicity.

PMID- 8571404
TI  - Mechanisms of selective copper removal by tetrathiomolybdate from metallothionein
      in LEC rats.
AB  - Copper (Cu) was selectively removed from metallothionein (MT) in the liver of LEC
      rats (Long-Evans rats with a cinnamon-like coat color) in vivo and in vitro by
      tetrathiomolybdate (TTM). Female LEC rats were injected intraperitoneally with
      TTM at a dose of 10 mg/kg body weight for 8 consecutive days. More than 2/3 of
      the Cu accumulating in the liver was removed by TTM treatment 24 h after the last
      injection. Although most Cu was bound to MT in the soluble fraction before TTM
      treatment, the Cu remaining in the liver was present almost exclusively in the
      non-soluble fraction together with molybdenum (Mo). Cu,Zn,Cd-MT was separated
      from the liver of LEC rats that had been injected with cadmium (Cd) and reacted
      with TTM at mol ratios of 0, 0.25, 0.50, 1.0, 2.0 and 4.0 to Cu bound to MT for
      10 min at 37 degrees C. When TTM was added at a mol ratio of less than 1.0, a
      Cu,Zn,Cd-MT/TTM complex was detected, while addition of TTM at a mol ratio of
      greater than 1.0 selectively removed Cu from MT and produced a Cu/TTM complex via
      liberation of Zn,Cd-MT from the Cu,Zn,Cd-MT/TTM complex. Excessive TTM appeared
      to facilitate polymerization of the Cu/TTM complex to insoluble polymers. The
      dose-related formation of differing MT/TTM complexes explains the findings
      observed in vivo.

PMID- 8571405
TI  - Oxidation of pyridine nucleotides is an early event in the lethality of allyl
      alcohol.
AB  - The involvement of altered pyridine nucleotide concentrations in the
      cytolethality of allyl alcohol was studied in isolated rat hepatocytes. NAD+,
      NADH, NADP+, NADPH and viability loss (leakage of lactate dehydrogenase into the
      medium) were measured in cells incubated with 0.5 mM allyl alcohol with or
      without the addition of 2 mM dithiothreitol at 30 min. Exposure to allyl alcohol
      increased NADH levels in the first 15 min of incubation. A sharp drop in NADH and
      NADPH with an accumulation of NADP+ occurred between 30 and 60 min of incubation
      with allyl alcohol, indicating an oxidation and interconversion of pyridine
      nucleotides. Dithiothreitol prevented the oxidation of pyridine nucleotides, but
      not their reduction or interconversion, and protected against cell killing by
      allyl alcohol. The results suggest that pyridine nucleotide oxidation might be
      important for allyl alcohol-induced cytotoxicity; however, a causal relationship
      between pyridine nucleotide oxidation and cell killing is yet to be demonstrated.

PMID- 8571406
TI  - Assessment of the protective activity of monisoamyl meso-2,3-dimercaptosuccinate
      against methylmercury-induced maternal and embryo/fetal toxicity in mice.
AB  - The protective activity of monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS), a
      new monoester of 2,3-dimercaptosuccinic acid (DMSA), on methylmercury-induced
      maternal and developmental toxicity was assessed in mice. A series of four Mi
      ADMS injections was given s.c. at 0.25, 6, 24, and 48 h after oral administration
      of 25 mg/kg of methylmercury chloride (MMC) given on day 10 of gestation. Mi-ADMS
      effectiveness was tested at 0, 23.8, 47.6 and 95 mg/kg. Cesarean sections were
      performed on gestation day 18. All live fetuses were examined for external,
      internal, and skeletal abnormalities. Oral MMC administration resulted in an
      increase in the number of resorptions, and a decrease in fetal body weight,
      whereas the incidence of cleft palate, micrognathia, and skeletal variations was
      also increased in the fetuses of the MMC-treated groups. Although significant
      amelioration of MMC-induced embryolethality by Mi-ADMS was not noted at any dose,
      MMC-induced fetotoxicity was reduced by administration of this agent at 23.8,
      47.6, and 95 mg/kg. However, the intrinsic toxicity of Mi-ADMS would be a
      restrictive factor for the possible therapeutic use of this chelator in pregnant
      women exposed to organic mercury.

PMID- 8571407
TI  - Induction of hepatic cytochrome P4502E1 in rats by acetylsalicylic acid or sodium
      salicylate.
AB  - Studies were conducted on the mechanism of the ethanol-inducible cytochrome P450
      (cytochrome P4502E1, CYP 2E1) induction by acetylsalicylic acid (ASA) or its
      metabolite salicylate (SAL). Many exogenous inducers of CYP 2E1 seem to increase
      CYP 2E1 by post-transcriptional activation without elevation of its mRNA level.
      Administration of a single high dose of ASA or SAL produces a significant
      increase in the activity of the hepatic microsomal p-nitrophenol hydroxylase in
      rats. Pretreatment of ASA-treated rats with a blocker of mRNA transcription,
      actinomycin D, or a blocker of protein synthesis, cycloheximide, markedly
      suppressed this enhanced activity of microsomal p-nitrophenol hydroxylase. The
      CYP 2E1 mRNA levels in livers of control rats and rats treated with ASA or SAL
      were measured by Northern blot analysis. Significantly elevated CYP 2E1 mRNA
      levels were measured in livers of treated rats compared with mRNA amounts of the
      control group. These data suggest that mRNA elevation seems to be characteristic
      for ASA induction, while other inducing agents show different patterns and
      mechanisms of activation.

PMID- 8571408
TI  - Concern about safety of carotid angioplasty.

PMID- 8571409
TI  - Changed incidence and case-fatality rates of first-ever stroke between 1970 and
      1993 in Tartu, Estonia.
AB  - BACKGROUND AND PURPOSE: The incidence of stroke has stabilized or increased in
      several developed countries recently, but few data about the trends are available
      from Eastern Europe. The study was designed to evaluate the possible changes of
      stroke incidence in Estonia. METHODS: A population-based stroke registry was
      conducted in Tartu during 1991 through 1993 (mean population, 110,631) to compare
      it with the study of 1970 through 1973 (population, 90,459). The majority of
      stroke patients were recorded prospectively, and most were hospitalized and
      evaluated by a neurologist. All available medical records were reviewed. Only
      first-ever stroke cases were registered. RESULTS: A total of 667 patients in 1970
      through 1973 and 829 patients in 1991 through 1993 were recorded. The total
      annual incidence per 100,000 rose from 221 to 250 (P = .0173). The total rate for
      men increased nonsignificantly from 183 to 209 and for women from 258 to 284.
      Significant increases were observed for men aged 50 to 59 years and for women
      aged 50 to 69 years; for persons over 70 years, the rates slightly declined. The
      case-fatality rate at 1 month declined significantly, from 49% to 30%.
      CONCLUSIONS: A remarkable increase in the incidence and decline in the case
      fatality rate of first-ever stroke was observed in Tartu, Estonia. The increase
      of incidence for those younger than 70 years could be due to the increased
      prevalence of risk factors. The decline in case fatality could theoretically be
      related to better management of secondary complications.

PMID- 8571410
TI  - Fish consumption and stroke in men. 30-year findings of the Chicago Western
      Electric Study.
AB  - BACKGROUND AND PURPOSE: Evidence of a relationship of fish intake to stroke
      incidence or mortality is weak. This report examines the association of fish
      consumption with stroke. METHODS: A cohort of 2107 men aged 40 to 55 years from
      the Chicago Western Electric Study who were free of coronary heart disease and
      stroke through their first annual reexamination was investigated in relation to
      baseline fish intake and 30-year risk of fatal and nonfatal stroke. Data on
      baseline fish intake, categorized into four levels (> or = 35 g/d, 18 to 34 g/d,
      1 to 17 g/d, and 0 g/d), were available for 1847 men. Average values of
      macronutrients and micronutrients from the first two examinations and major
      coronary and stroke risk factors were assessed in relation to fish consumption.
      Stroke mortality was ascertained from death certificates and nonfatal stroke from
      records of the Health Care Financing Administration. RESULTS: During 46,426
      person-years of follow-up, 76 stroke deaths occurred. Men consuming > or = 35 g/d
      of fish (highest level) had a higher age-adjusted death rate from stroke (23.5
      per 10,000 person-years) than men in the three other categories of fish
      consumption. Based on a Cox proportional hazards regression model with adjustment
      for age, systolic blood pressure, cigarette smoking, serum cholesterol level,
      diabetes, electrocardiographic abnormalities, and table salt use, hazards ratios
      (and 95% confidence intervals) for fish consumers compared with nonconsumers were
      1.34 (0.53 to 3.41) for > or = 35 g/d, 0.96 (0.41 to 2.21) for 18 to 34 g/d, and
      1.00 (0.43 to 2.33) for 1 to 17 g/d. Age-adjusted and multivariate analyses for
      fatal and nonfatal strokes (n = 222) yielded similar results. CONCLUSIONS: With
      stroke rates highest in the subgroup reporting highest fish intake, these data do
      not support the hypothesis of an inverse association of fish consumption with
      strokes.

PMID- 8571411
TI  - Diabetes mellitus as a risk factor for death from stroke. Prospective study of
      the middle-aged Finnish population.
AB  - BACKGROUND AND PURPOSE: High blood pressure is the most important risk factor for
      stroke. It is also known that diabetic patients are at increased risk of both
      hypertension and stroke. The aim of this study was to assess the independent
      effect of diabetes as a risk factor for stroke. Results from the previous studies
      of this question have been somewhat inconclusive. METHODS: We performed a
      prospective study (average follow-up, 16.4 years) of 8077 men and 8572 women who
      had participated in risk factor surveys in Eastern Finland in 1972 (20 years of
      follow-up) and 1977 (15 years of follow-up). Risk factors included in the current
      analyses were smoking, blood pressure, antihypertensive drug treatment, serum
      total cholesterol, and diabetes either at baseline or developed during the follow
      up. Age- and risk factor-adjusted relative risks for death of stroke were
      determined with the Cox proportional hazards model. RESULTS: Diabetes mellitus
      was the strongest risk factor for death from stroke among both men and women in
      univariate and multivariate analyses. In addition, smoking and systolic blood
      pressure appeared to be independent risk factors among both sexes, as did serum
      total cholesterol among men. Men with diabetes at baseline appeared to be at a
      sixfold increased risk of death from stroke, while relative risk for men who
      developed diabetes during the follow-up was 1.7. In women, those who were
      diabetic at baseline were at higher risk of stroke than women who developed
      diabetes later (relative risks, 8.2 and 3.7, respectively). Of stroke deaths, 16%
      in men and 33% in women were attributed to diabetes. CONCLUSIONS: Diabetic
      subjects have a very high risk of death from stroke, particularly women. Our data
      also suggest that the duration of diabetes is an important factor contributing to
      the risk of stroke.

PMID- 8571412
TI  - Influence of apolipoprotein E genotype on cerebral amyloid angiopathy in the
      elderly.
AB  - BACKGROUND AND PURPOSE: The inheritance of the epsilon 4 allele of the
      apolipoprotein E gene (APOE) is associated with increased risk of developing
      dementia of the Alzheimer type (DAT). We have investigated whether the APOE
      genotype influences the severity of cerebral amyloid angiopathy (CAA) in elderly
      individuals with or without DAT. METHODS: From a consecutive autopsy series, we
      studied 88 patients (85.2 +/- 8.1 years) without degenerative disorders other
      than DAT. The percentages of amyloid-laden vessels in the occipital lobes were
      calculated and compared between APOE genotypes. RESULTS: For epsilon 3/3 and
      epsilon 3/4 genotypes, there was a trend toward increased CAA in epsilon 3/4
      individuals for non-DAT and conversely in epsilon 3/3 individuals for DAT
      patients, but these did not achieve significance. CONCLUSIONS: The present study
      suggests that the epsilon 4 allele is not a strong risk factor for CAA in elderly
      people.

PMID- 8571413
TI  - Hyperinsulinism and cerebral microangiopathy.
AB  - BACKGROUND AND PURPOSE: High insulin levels are a recognized risk factor for
      atherosclerosis. Microvascular endothelium is more susceptible to metabolic and
      mitogenic effects of insulin than large-vessel endothelium. Besides their
      atherogenic effect, high insulin levels impair fibrinolysis by enhancing
      plasminogen activator inhibitor-1. We undertook this study to evaluate the
      hypothesis that elevated serum insulin and C-peptide levels are related to
      cerebral small-vessel disease rather than large-vessel pathology. METHODS: One
      hundred ninety-four consecutive patients presenting with symptomatic
      cerebrovascular disease were assigned to three subgroups that were differentiated
      by clinical presentations, brain imaging studies, and extracranial as well as
      transcranial vascular ultrasound findings: (1) patients with lacunes (n = 20),
      (2) patients with subcortical arteriosclerotic encephalopathy (n = 35), and (3)
      patients with strokes due to large-vessel disease (n = 99). Patients who had
      suffered a cryptogenic (n = 9) or cardioembolic (n = 16) stroke or who showed
      characteristics of the microangiopathy and macroangiopathy groups (n = 15) were
      not further evaluated. Thirty patients without manifestations of cerebrovascular
      disease were also examined. Fasting blood glucose, insulin, and C-peptide levels
      were determined in all subjects. RESULTS: There were no significant differences
      in age or sex among the three groups and control patients. Insulin levels were
      significantly higher in the lacunar group compared with the subcortical
      arteriosclerotic encephalopathy group, the macroangiopathy group, and the control
      patients (median [interquartile range]: 103.8 [198.6], 72.0 [103.2], 66.0 [57.0],
      and 52.2 [57.0] pmol/L, respectively; all P < .05, Mann-Whitney test). There was
      a statistically significant difference in insulin concentrations between the
      microangiopathy group (subcortical arteriosclerotic encephalopathy and lacunes)
      and the macroangiopathy and control groups (81.0 [110.4], 66.0 [57.0], and 55.2
      [57.0] pmol/L, respectively; all P < .05, Mann-Whitney). The same was true for
      the distribution of C-peptide levels and to a minor extent blood glucose values,
      but these differences failed to reach statistical significance. CONCLUSIONS:
      Elevated insulin levels potentially represent a pathogenetic factor in the
      development of cerebral small-vessel disease, predominantly in patients
      presenting with lacunes. Whether this is due solely to atherosclerotic changes of
      the small penetrating arteries or whether changes in hemorheology are operative
      as well remains to be evaluated.

PMID- 8571414
TI  - Thickening of the carotid wall. A marker for atherosclerosis in the elderly?
      Cardiovascular Health Study Collaborative Research Group.
AB  - BACKGROUND AND PURPOSE: We investigated the relationships between prevalent
      coronary heart disease (CHD), clinically manifest atherosclerotic disease (ASD),
      and major established risk factors for atherosclerosis and intima-media thickness
      (IMT) in the common carotid arteries (CCA) and internal carotid arteries (ICA)
      separately and in combination in older adults. We wished to determine whether a
      noninvasive measurement can serve as an indicator of clinically manifest
      atherosclerotic disease and to determine which of the two variables, CCA IMT or
      ICA IMT, is a better correlate. METHODS: IMT of the CCA and ICA was measured with
      duplex ultrasound in 5117 of 5201 individuals enrolled in the Cardiovascular
      Health Study, a study of the risk factors and the natural history of
      cardiovascular disease in adults aged 65 years or more. Histories of CHD,
      peripheral arterial disease, and cerebrovascular disease were obtained during
      baseline examination. Risk factors included cholesterol levels, cigarette
      smoking, elevated blood pressure, diabetes, age, and sex. Relationships between
      risk factors and IMT were studied by multiple regression analysis and canonical
      variate analysis. Prediction of prevalent CHD and ASD by IMT measurements in CCAs
      and ICAs were made by logistic regression, adjusting for age and sex. RESULTS:
      IMT measurements of the CCAs and ICAs were greater in persons with CHD and ASD
      than those without, even after controlling for sex (P < .001). IMT measurements
      in the ICA were greater than those in the CCA. Risk factors for ASD accounted for
      17% and 18% of the variability in IMT in the CCA and ICA, respectively. These
      same risk factors accounted for 25% of the variability of a composite measurement
      consisting of the sum of the ICA IMT and CCA IMT. The ability to predict CHD and
      ASD was greater for ICA IMT (odds ratio [confidence interval]: 1.36 [1.31 to
      1.41] and 1.35 [1.25 to 1.44], respectively) than for CCA IMT (1.09 [1.05 to
      1.13] and 1.17 [1.09 to 1.25]). CONCLUSIONS: Whereas CCA IMT is associated with
      major risk factors for atherosclerosis and existing CHD and ASD in older adults,
      this association is not as strong as that for ICA IMT. The combination of these
      measures relates more strongly to existing CHD and ASD and cerebrovascular
      disease risk factors than either taken alone.

PMID- 8571415
TI  - Agreement on disease-specific criteria for do-not-resuscitate orders in acute
      stroke. Members of the Canadian and Western New York Stroke Consortiums.
AB  - BACKGROUND AND PURPOSE: The do-not-resuscitate (DNR) order is a mechanism of
      withholding cardiopulmonary resuscitation (CPR). The lack of DNR guidelines
      specific for acute stroke may result in many stroke patients receiving
      unnecessary and futile resuscitation and ventilator-assisted breathing. METHODS:
      A prospective multicenter evaluation of disease-specific criteria for DNR orders
      in acute stroke was initiated using a modified Delphi process. The participants
      were the Canadian and Western New York Stroke Consortium members who are closely
      involved in caring for acute stroke patients and conducting clinical trials at
      the academic centers. Previously published provisional criteria were reviewed by
      the participants. Modifications were made to the criteria until statistically
      significant agreement (P < .05, z score, or 67% similar answers) was achieved.
      RESULTS: Disease-specific criteria for DNR orders in acute stroke were discussed
      by 26 physicians in three rounds of the opinion survey. An agreement was reached
      that a "no resuscitation" decision is appropriate when any two of the following
      three clinical criteria are present (the degree of agreement is given in
      parentheses): severe stroke (88%, P = .00007), life-threatening brain damage
      (73%, P < .01), and significant comorbidities (92%, P = .00003). The poor
      prognosis implied by these criteria should be discussed whenever possible among
      physician(s), the patient, and family members before the decision to withhold CPR
      is made. Eighty-one percent of the participants agreed that these disease
      specific criteria are appropriate for clinical use (P = .0008). CONCLUSIONS:
      Disease-specific criteria for DNR orders were developed to supplement general DNR
      policies for patients with hemispheric brain infarction and intracerebral
      hemorrhage during the first 2 weeks of stroke. A significant agreement was
      reached by a panel of physicians that patients with acute stroke should not be
      resuscitated if these disease-specific criteria are met.

PMID- 8571416
TI  - Interobserver agreement in the classification of stroke in the physicians' health
      study.
AB  - BACKGROUND AND PURPOSE: The evaluation of cerebrovascular end points in
      prospective studies is often based exclusively on medical record examination and
      may be made by more than one observer over time. To address the issues of
      adequacy of medical record information and consistency in diagnosis over time, we
      evaluated interobserver agreement for the main items of the stroke classification
      system used in the Physicians' Health Study. This trial included 22,071
      physicians randomly assigned in 1982 to receive either aspirin or placebo to
      assess the subsequent risk of cardiovascular events, including stroke. METHODS:
      Stroke subtype, stroke severity, and certainty of diagnosis were first classified
      from medical records from the years 1982 through 1988. The 216 stroke events
      reported in this period were independently reclassified in 1994 and compared with
      the initial classification using kappa statistics. RESULTS: Overall agreement in
      major stroke types (hemorrhagic, ischemic, undetermined stroke) as well as in
      hemorrhagic stroke subtypes was excellent (kappa = 0.81 and kappa = 0.95,
      respectively). A wide range of values for the ischemic stroke subtypes (kappa =
      0.13 to kappa = 0.96) was obtained. Agreement was substantial in assessment of
      stroke severity (kappa = 0.71), and it was fair (kappa = 0.33) for certainty of
      diagnosis. CONCLUSIONS: Interobserver agreement is high for major stroke types as
      well as for categories of hemorrhagic stroke on the basis of review of medical
      records and results of imaging data. The classification of ischemic stroke
      subtypes, however, is subject to substantial interobserver disagreement. Periodic
      reclassification of random samples of end points might be considered in long-term
      prospective studies to assess potential misclassification of events by different
      observers.

PMID- 8571417
TI  - Long-term prognosis in cerebral venous thrombosis. Follow-up of 77 patients.
AB  - BACKGROUND AND PURPOSE: Very little is known about the long-term outcome of
      patients with cerebral venous thrombosis (CVT), particularly regarding the risk
      of residual epilepsy and further thrombotic events. We retrospectively studied 77
      patients with CVT diagnosed by angiography and/or MRI. METHODS: A cohort of 77
      patients aged 18 to 77 (mean, 38.5) years with CVT, evaluated from 1975 through
      1990, was followed up for a mean of 77.8 months (range, 14 to 204 months; median,
      63 months). Information on death, neurological status, seizures, recurrent CVT,
      other thrombotic events, and subsequent pregnancies was obtained from direct
      observation, mail questionnaire, or telephone interviews. RESULTS: Sixty-six of
      77 patients (85.7%) had no neurological sequelae during follow-up. Eleven
      patients (14.3%) remained neurologically impaired. Two who initially presented
      with isolated intracranial hypertension had blindness due to optic atrophy. The
      other 9 had focal signs at the time of CVT and were left with various cognitive
      or focal deficits. Four of 28 (14.3%) patients who had seizures at the acute
      stage had recurrent seizures. One of the 51 patients with lateral sinus
      thrombosis developed a dural arteriovenous fistula. Nine of the 77 patients
      (11.7%) suffered a second CVT, all but one in the first year. Noncerebral
      thrombotic events occurred in 11 patients (14.3%). No recurrence of CVT occurred
      during later pregnancies, but 1 patient had a postpartum deep vein thrombosis.
      CONCLUSIONS: In the present series, CVT has an essentially good long-term
      prognosis. The frequency of long-standing epilepsy was low, suggesting that long
      term anticonvulsant treatment is not necessary in the majority of cases. A second
      CVT or another thrombotic episode occurred in 20% of patients, stressing the need
      in a minority of cases for long-term anticoagulation.

PMID- 8571418
TI  - Reduced heart rate variability after right-sided stroke.
AB  - BACKGROUND AND PURPOSE: Recently, asymmetries have been demonstrated in skin
      sudomotor and vasomotor function after unilateral cerebral lesions. The present
      study was performed to determine whether other bedside tests reflecting
      sympathetic and parasympathetic cardiovascular functions would reveal differences
      with respect to the side of cerebrovascular lesions. METHODS: Heart rate
      variability during deep breathing as well as blood pressure and heart rate
      changes during tilt and isometric handgrip was measured in a group of patients
      with a monofocal stroke and compared with similar data from age-matched patients
      with transient ischemic attack and healthy control subjects. RESULTS: Compared
      with left-sided stroke and with the control subjects, stroke location on the
      right side was associated with a reduced respiratory heart rate variability (P >
      .01), a reflex mainly under parasympathetic control. In contrast, reflexes mainly
      reflecting peripheral sympathetic function were equal for right- and left-sided
      lesions. CONCLUSIONS: Since an imbalance in cardiac autonomic innervation may be
      crucial for the generation of cardiac arrhythmias and since reduced heart rate
      variability has been associated with increased mortality, the findings suggest
      that the risk of sudden death may be correlated with lateralization and location
      of the brain infarct after stroke.

PMID- 8571419
TI  - Sleep-disordered breathing and poor functional outcome after stroke.
AB  - BACKGROUND AND PURPOSE: We objectively evaluated patients with recent stroke to
      determine the prevalence of sleep-disordered breathing (SDB) and whether SDB was
      associated with unfavorable clinical outcomes. METHODS: Forty-seven patients with
      recent ischemic stroke (median, 13 days) were studied with computerized overnight
      oximetry for evidence of arterial oxyhemoglobin desaturation (SaO2).
      Polysomnography was also performed on 19 patients. Medical history, sleep
      history, location of stroke, and severity of neurological deficit were recorded,
      and patients were observed by staff for evidence of snoring and excessive daytime
      sleepiness. Functional abilities were measured with the use of the Barthel Index
      (BI). Outcome variables included ability to return home at discharge, continued
      residence at home at 3 and 12 months, BI at discharge, BI at 3 and 12 months, and
      death from any cause at 12 months. RESULTS: Mean SaO2 during oximetry was 94.0 +/
      1.7%, and percentage of recording time spent at < 90% SaO2 was 4.3 +/- 5.7%. The
      number of desaturation events per hour of recording time (desaturation index
      [DI]) was 9.5 +/- 9.67, with 15 of 47 (32%) having DI > 10 and 6 of 47 (13%)
      having DI > 20. Oximetry measures of SDB correlated with lower BI scores at
      discharge and lower BI at 3- and 12-month follow-ups (P < or = .05, Pearson
      coefficients). Oximetry measures correlated with return home after discharge, but
      the association between oximetry measures and living at home was lost at 12
      months. Two oximetry variables correlated with death at 1 year. Brain stem
      location correlated with higher DI and time at < 90% SaO2, but patients with
      hemispheric stroke and oximetry abnormalities also had worse functional outcome.
      No correlation was found between oximetry values and sex, age, preexisting
      medical conditions (except previous stroke), or severity of neurological deficit.
      Oximetry abnormalities were associated with a history of snoring. Polysomnography
      on 19 patients confirmed oximetry evidence of severe SDB. Eighteen of 19 patients
      (95%) had an apnea-hypopnea index (AHI) of > 10 events per hour of recording, 13
      of 19 (68%) had an AHI > 20, and 10 of 19 (53%) had an AHI > 30. Desaturation
      events were largely due to obstructive apneas. CONCLUSIONS: SDB accompanied by
      arterial oxyhemoglobin desaturation is common in patients undergoing
      rehabilitation after stroke and is associated with higher mortality at 1 year and
      lower BI scores at discharge and at 3 and 12 months after stroke. SDB may be an
      independent predictor of worse functional outcome. Obstructive sleep apnea
      appeared to be the most common form of SDB, and the frequent history of snoring
      suggests that SDB preceded the stroke in most patients.

PMID- 8571420
TI  - A systematic review of the risks of stroke and death due to endarterectomy for
      symptomatic carotid stenosis.
AB  - BACKGROUND AND PURPOSE: Carotid endarterectomy reduces the risk of carotid
      territory ischemic stroke ipsilateral to a recently symptomatic severe carotid
      stenosis. However, the benefit is limited by the risks of stroke and death
      associated with the operation. Although reported surgical risks vary enormously,
      there has been no systematic review of the published literature. METHODS: We
      performed a systematic review of mortality and the risk of stroke and/or death
      due to endarterectomy for symptomatic carotid stenosis in studies published since
      1980. RESULTS: Fifty-one studies fulfilled our criteria. Overall mortality was
      1.62% (95% confidence interval [CI], 1.3 to 1.9), and the risk of stroke and/or
      death was 5.64% (95% CI, 4.4 to 6.9). However, there was significant
      heterogeneity of risk of stroke and/or death (P < .001). The risk varied
      systematically with the methods and the authorship of the study. The risk of
      stroke and/or death was highest in studies in which patients were assessed by a
      neurologist after surgery (7.7%; 95% CI, 5.0 to 10.2) and lowest in studies with
      a single author affiliated with a department of surgery (2.3%; 95% CI, 1.8 to
      2.7). After correcting for study methodology, there was no temporal trend in the
      risk of stroke and/or death between 1980 and 1995. CONCLUSIONS: The reported
      risks of endarterectomy for symptomatic carotid stenosis show significantly
      greater variability than would be expected by chance. However, much of this
      variability can be accounted for by differences in methodology and authorship.
      The 5.6% overall risk of stroke and/or death is consistent with present
      guidelines.

PMID- 8571421
TI  - A systematic comparison of the risks of stroke and death due to carotid
      endarterectomy for symptomatic and asymptomatic stenosis.
AB  - BACKGROUND AND PURPOSE: There is some evidence that carotid endarterectomy
      reduces the risk of ipsilateral carotid territory ischemic stroke in patients
      with severe asymptomatic carotid stenosis. However, the benefit of endarterectomy
      is dependent on a low risk of stroke and/or death due to surgery. Whether the low
      operative risks reported in recent clinical trials and cited in recent guidelines
      are widely generalizable to clinical practice is unclear. Is endarterectomy for
      asymptomatic carotid stenosis really safer than surgery for recently symptomatic
      stenosis? METHODS: We performed a systematic review comparing the risks of stroke
      and death due to carotid endarterectomy, performed by the same surgeons or in the
      same institutions, for symptomatic and asymptomatic stenosis in studies published
      since 1980. RESULTS: Twenty-five studies fulfilled our criteria. Mortality within
      30 days of endarterectomy was 1.31% for asymptomatic stenosis and 1.81% for
      symptomatic stenosis (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.49
      to 0.99). The risks of fatal stroke were 0.47% and 0.91%, respectively (OR, 0.57;
      95% CI, 0.34 to 0.98). The overall risk of stroke and/or death was 3.35% for
      asymptomatic and 5.18% for symptomatic stenosis (OR, 0.61; 95% CI, 0.51 to 0.74).
      CONCLUSIONS: Mortality and the risk of stroke and/or death due to carotid
      endarterectomy are significantly lower for asymptomatic than symptomatic
      stenosis. These findings are consistent across virtually all studies and are
      likely to be widely generalizable.

PMID- 8571422
TI  - Generalized anxiety disorder in stroke patients. A 3-year longitudinal study.
AB  - BACKGROUND AND PURPOSE: This prospective study examined the prevalence and
      longitudinal course of generalized anxiety disorder (GAD) after stroke and its
      comorbidity with major depression over time. The contributions of lesion
      characteristics, functional impairment, and psychosocial factors to the
      development of GAD after stroke were studied. METHODS: In a population-based
      cohort of 80 patients with acute stroke, we assessed GAD and comorbid major
      depression, functional ability, and social network at regular time points over 3
      years. Cerebral atrophy and brain lesion parameters were determined from CT scans
      performed at the acute stage and after 3 years. RESULTS: The prevalence of GAD
      after stroke was 28% in the acute stage, and there was no significant decrease
      through the 3 years of follow-up. At 1 year, only 23% of the patients with early
      GAD (0 to 3 months) had recovered; those not recovered at this follow-up had a
      high risk of a chronic development of the anxiety disorder. Comorbidity with
      major depression was high and seemed to impair the prognosis of depression. At
      the acute stage after stroke, GAD plus depression was associated with left
      hemispheric lesion, whereas anxiety alone was associated with right hemispheric
      lesion. Cerebral atrophy was associated with both depression and anxiety disorder
      late but not early after stroke. Dependence in activities of daily living and
      reduced social network were associated with GAD at all follow-up periods except
      at the acute stage. CONCLUSIONS: GAD after stroke is a common and long-lasting
      affliction that interferes substantially with social life and functional
      recovery. There is a differentiation of factors implicated in its development
      based on the period of time since the stroke event.

PMID- 8571423
TI  - Craniotomy for intracranial aneurysm and subarachnoid hemorrhage. Is course,
      cost, or outcome affected by age?
AB  - BACKGROUND AND PURPOSE: Age may influence cost or effectiveness of treatment for
      subarachnoid hemorrhage (SAH). This study examined the effect of age on both.
      METHODS: Patients (n = 219) who underwent craniotomy for intracranial aneurysm
      and SAH over 6 years at one tertiary care center were divided in two ways by age:
      single advanced age (< 65 years and > or = 65 years) and decade of age (23 to 39,
      40 to 49, 50 to 59, 60 to 69, and 70 to 81 years). Data recorded for each patient
      included numbers of procedures and complications in the surgical intensive care
      unit (SICU), number of days in the SICU and the hospital, costs for SICU and ward
      care, total cost (SICU plus ward costs), and the Acute Physiology and Chronic
      Health Evaluation (APACHE) II score at admission and discharge, the Hunt-Hess
      grade at admission and immediately preoperatively, and quality of life score, a
      measure of outcome. Mortality rates by age group were calculated. RESULTS: The
      only variable significantly affected by decade of age was mortality rate, which
      increased as decade of age increased (3% to 17%). With the 65-year comparison,
      mortality rate, cost, APACHE II score at admission and discharge, days before
      operation, and days in the SICU were significantly higher for age > or = 65
      years. CONCLUSIONS: Whereas mortality is higher for the older age group, quality
      of life scores appear acceptable for those who survive. Even though the hospital
      costs of treating elderly patients for SAH may be higher than those for younger
      patients, this should not be used to justify withholding care from the elderly.

PMID- 8571424
TI  - Preoperative and postoperative evaluation of cerebral perfusion and vasodilatory
      capacity with 99mTc-HMPAO SPECT and acetazolamide in childhood Moyamoya disease.
AB  - BACKGROUND AND PURPOSE: The results of long-term follow-up studies of cerebral
      perfusion and vasodilatory capacity following administration of acetazolamide
      after serial vascular reconstructions in 25 patients with childhood moyamoya
      disease are reported. METHODS: Cerebral perfusion was measured with 99mTc
      hexamethylpropyleneamine oxime single-photon emission CT before and after IV
      administration of 10 mg/kg acetazolamide, which was performed both before and
      after vascular reconstruction by superficial temporal artery-middle cerebral
      artery anastomosis and encephalomyosynangiosis (first and second operations)
      and/or omental transplantation to the brain (third operation). RESULTS: Follow-up
      periods ranged between 12 and 24 months (mean +/- SD, 18.5 +/- 3.2 months) after
      the first operation. Repetitive transient ischemic attacks disappeared completely
      after serial vascular reconstructions in all patients. Before the first
      operation, cerebral perfusion in the territory of the middle cerebral artery on
      the side of initial operation was 83.9 +/- 4.7% and was significantly lower than
      that in the contralateral side (88.3 +/- 4.9%, n = 25; P < .0001, paired t test).
      Vasodilatory capacity on the side of the first operation was -18.4 +/- 2.5% and
      that on the contralateral side -14.4 +/- 2.1%. The former value was significantly
      lower than the latter value (n = 25; P < .0001, paired t test). After the first
      operation, cerebral perfusion and vasodilatory capacity on the side of initial
      operation were markedly improved, to 87.8 +/- 4.5% and -14.7 +/- 2.7%,
      respectively (n = 25; P < .0001, both cases, paired t test). Before the second
      operation, cerebral perfusion and vasodilatory capacity on the side of the second
      operation were 76.6 +/- 4.1% and -20.1 +/- 1.9%, respectively, and significantly
      lower than those before the first operation (n = 25; P < .0001, both cases,
      paired t test). Eight patients subsequently required bifrontal omental
      transplantation for repetitive paraparetic transient ischemic attacks after the
      second operation; they had low cerebral perfusion and vasodilatory capacity
      bilaterally in the territories of the anterior cerebral arteries (72.4 +/- 2.7%
      and -18.6 +/- 1.7%, respectively). After omental transplantation, both were
      significantly increased, to 81.9 +/- 3.4% and -11.8 +/- 1.9%, respectively (n =
      25; P < .0001, both cases, paired t test). CONCLUSIONS: Hemodynamic compromise
      existed in patients with childhood moyamoya disease and was a major cause of
      development of ischemic symptoms. Regions in which hemodynamic compromise was
      present could be determined by measuring regional cerebral perfusion and
      vasodilatory capacity.

PMID- 8571425
TI  - Evaluation of extracranial vertebral artery dissection with duplex color-flow
      imaging.
AB  - BACKGROUND AND PURPOSE: We describe the diagnostic potential of duplex color-flow
      imaging in the evaluation of extracranial vertebral artery dissection. METHODS:
      Twenty patients with 24 extracranial vertebral artery dissections (four
      bilateral) were examined with duplex ultrasonography over a period of 6 years.
      Color-flow imaging was carried out in 16 of these patients. In 15 patients (75%),
      the dissection was temporally related to trauma. Angiography was available in 18
      patients, confirming the diagnosis. RESULTS: In 15 patients, the diagnosis was
      primarily established with ultrasonography. Five patients with a dissection were
      referred for follow-up color-flow examinations. Six vertebral arteries were
      dissected at the origin or in the proximal V1 segment, one in the distal V2
      segment, and one at the atlas loop. In contrast to other studies, the most
      frequent localization of the dissection in our patients was the region between
      the V1 and V2 segments (n = 16), where the most typical dissection site was the
      entrance of the artery into the transverse foramen of the C6 vertebra (n = 11).
      Typical ultrasonographic findings were irregular stenosis, dissecting membrane
      with true and false lumen, localized increase in diameter of the artery,
      pseudoaneurysm, intramural hematoma, and tapering stenosis with distal occlusion.
      In follow-up examination, a good regression of pathological findings was found in
      17 dissections (70.8%). Two occlusions were completely recanalized. CONCLUSIONS:
      Extracranial vertebral artery dissections can be diagnosed noninvasively with
      duplex color-flow imaging. It is therefore a useful method for early diagnosis
      and follow-up examination.

PMID- 8571426
TI  - Vasomotor reactivity and pattern of collateral blood flow in severe occlusive
      carotid artery disease.
AB  - BACKGROUND AND PURPOSE: The compromise of cerebrovascular autoregulation in
      severe occlusive carotid artery disease depends on the functional capacity of
      collateral pathways. In previous reports correlating hemodynamic disturbances
      with collateral pathways, collateral blood supply was often evaluated by invasive
      cerebral angiography. In this study noninvasive transcranial Doppler ultrasound
      was used to determine both collateral pathways and vasomotor reactivity. METHODS:
      With the use of blood flow direction, compression tests, and evident side-to-side
      asymmetries of blood velocities, the collateral supply through the anterior and
      posterior communicating arteries, the ophthalmic artery, and leptomeningeal
      anastomoses was evaluated by transcranial Doppler ultrasound in 48 patients (42
      men, 6 women; mean +/- SD age, 59 +/- 9 years) with occlusion (n = 36) or
      stenosis of more than 90% (n = 12) of one internal carotid artery. Ipsilateral
      vasomotor reactivity was determined by the percent increase of middle cerebral
      artery mean blood velocity with the use of (1) the breath-holding maneuver and
      (2) acetazolamide (1 g IV) as vasodilatory stimulus. Additional stenoses (50% to
      < 90%) of the contralateral internal carotid artery were present in 20 of the 48
      patients. RESULTS: Vasomotor reactivity was not affected by the presence of a
      contralateral internal carotid artery stenosis. Both vasodilatory stimuli
      similarly indicated poor vasomotor reactivity when an ophthalmic or a
      leptomeningeal pathway accompanied an anterior communicating artery pathway
      compared with a lone anterior communicating artery pathway (P < .05). The
      acetazolamide challenge indicated significantly better preserved vasomotor
      reactivity when blood supply was provided through a lone anterior communicating
      artery pathway (66 +/- 30%) than through an anterior and posterior communicating
      artery pathway (33 +/- 20%, P < .05), whereas the breathholding method failed to
      show such a difference. CONCLUSIONS: The presence of an ophthalmic artery pathway
      may provide the first evidence of disturbed vasomotor reactivity. The use of
      cerebral angiography to evaluate collateral pathways must be considered carefully
      since transcranial Doppler ultrasound is a reliable noninvasive alternative.

PMID- 8571427
TI  - Low pulsatility signals through the orbits.
AB  - BACKGROUND AND PURPOSE: Low pulsatility signals (LPS) on transcranial Doppler
      ultrasonography are detected (1) with arteriovenous malformations, (2) distal to
      hemodynamically significant stenosis, and (3) in venous structures. We describe
      focal LPS in the territory of the internal carotid artery siphon that do not
      represent any of the above conditions. METHODS: We performed retrospective and
      prospective reviews of transcranial Doppler studies on 3225 patients over 5
      years. Clinical and radiological data of all patients with focal LPS were
      extracted. LPS was defined as a focal signal identified through the orbital
      windows with a low pulsatility index (< 0.6). RESULTS: Sixteen LPS (mean flow
      velocity [mean +/- SD], 62 +/- 11 cm/s; pulsatility index [mean +/- SD], 0.41 +/-
      0.08; depth range, 46 to 72 mm) from 15 patients (mean +/- SD age, 45 +/- 15
      years; 4 men, 11 women) were identified. LPS flow direction was away from the
      probe in 13 cases and toward it in 3. Presenting symptoms included headache,
      focal neurological deficits, dizziness, and pulsatile tinnitus. All patients had
      cranial MRI (MRI and MR angiography in 11). Three patients underwent conventional
      cerebral angiography. Arteriovenous malformations or significant arterial
      stenoses were not detected on any study. CONCLUSIONS: A focal signal from the
      internal carotid artery siphon region with low pulsatility index and normal mean
      flow velocity, identified in the absence of other transcranial Doppler
      abnormalities, is not related to an arteriovenous malformation or proximal
      arterial stenosis. LPS, as defined, are not of venous origin since mean flow
      velocity was in the arterial range. LPS are likely related to prominent venous
      flow in the cavernous sinus secondary to unusually strong pulsation of the
      intracavernous internal carotid artery.

PMID- 8571428
TI  - Heparin reduces neurological impairment after cerebral arterial air embolism in
      the rabbit.
AB  - BACKGROUND AND PURPOSE: Neurological injury after cerebral air embolism may be
      due to thromboinflammatory responses at sites of air-injured endothelium. Because
      heparin inhibits multiple thromboinflammatory processes, we hypothesized that
      heparin would decrease neurological impairment after cerebral air embolism.
      METHODS: To first establish a dose of air that would cause unequivocal
      neurological injury, anesthetized New Zealand White rabbits received either 0,
      50, 100, or 150 microL/kg of air into the internal carotid artery (n = 5 in each
      group). One hour later, anesthesia was discontinued. Animals were neurologically
      evaluated at 24 hours with the use of a scale ranging from 0 (normal) to 97
      (coma) points. In a subsequent experiment, anesthetized rabbits received either
      heparin (n = 17) or saline (n = 15) 5 minutes before air injection (150
      microL/kg). Heparin was given as a 200-IU/kg bolus and followed by a constant
      infusion of 75 IU.kg-1.h-1 for 2 hours. Equal volumes of saline were given to
      control rabbits. Two hours later, anesthesia was discontinued. Animals were
      neurologically evaluated 24 hours after air embolism. RESULTS: There was a
      monotonic relationship between dose of air and severity of neurological
      impairment at 24 hours (P = 1.1 x 10(-7)). Animals receiving 150 microL/kg of air
      were unequivocally injured (score, 60 +/- 16). In the second experiment, heparin
      animals had significantly less neurological impairment at 24 hours (34 +/- 14)
      than saline controls (52 +/- 8) (P = .0013). CONCLUSIONS: When given
      prophylactically, heparin decreases neurological impairment caused by severe
      cerebral arterial air embolism.

PMID- 8571429
TI  - Relaxation of subarachnoid hemorrhage-induced spasm of rabbit basilar artery by
      the K+ channel activator cromakalim.
AB  - BACKGROUND AND PURPOSE: Cerebral vasospasm resulting from subarachnoid hemorrhage
      (SAH) is refractory to most vasodilators. However, despite evidence that a
      mechanism underlying the vasospasm may be smooth muscle cell membrane
      depolarization resulting from decreased K+ conductance, the ability of K+ channel
      activators to relax the spasm has not been thoroughly investigated. The purpose
      of this study, therefore, was to investigate whether K+ channel activation
      selectively relaxes SAH-induced vasospasm. METHODS: Three days after SAH in the
      rabbit, relaxation of the basilar artery in response to the K+ channel activator
      cromakalim as well as to staurosporine (protein kinase C antagonist), forskolin
      (adenylate cyclase activator), and sodium nitroprusside (guanylate cyclase
      activator) was measured in situ with the use of a cranial window. Relaxation in
      response to these agents was also investigated in control vessels contracted with
      serotonin. Membrane potential of the smooth muscle cells of the basilar artery
      from SAH and control rabbit was measured in vitro with the use of intracellular
      microelectrodes. RESULTS: Cromakalim completely relaxed the SAH-induced spastic
      basilar artery, while staurosporine, forskolin, and sodium nitroprusside were
      significantly less efficacious. In contrast, sodium nitroprusside and forskolin
      were more efficacious relaxants in serotonin-contracted control vessels than in
      SAH vessels. The K+ channel blocker glyburide and high [K+] prevented cromakalim
      induced relaxation. Glyburide did not inhibit forskolin-induced relaxation of
      serotonin-contracted control vessels. Cromakalim concentration-dependently
      repolarized spastic basilar artery smooth muscle cells, and the repolarization
      was prevented by glyburide. CONCLUSIONS: These results suggest that K+ channel
      activation selectively relaxes SAH-induced vasospasm. We speculate that the
      ability of K+ channel activators to selectively relax the spasm may be due, at
      least in part, to the underlying inhibition of K+ channels after SAH.

PMID- 8571431
TI  - Functional outcome in rats transferred to an enriched environment 15 days after
      focal brain ischemia.
AB  - BACKGROUND AND PURPOSE: The aim was to determine whether a delayed transfer to an
      enriched environment improves outcome after focal brain ischemia. METHODS:
      Performance on a rotating pole, prehensile traction, limb placement, and postural
      reflexes were tested in 15 spontaneously hypertensive rats housed in standard
      laboratory cages for 2 weeks after middle cerebral artery ligation. Seven of the
      15 rats were then transferred to an enriched environment, and the two groups were
      tested 1, 3, and 5 weeks later. RESULTS: The enriched environment significantly
      improved pole performance, prehensile traction, and limb placement. CONCLUSIONS:
      Delayed postoperative environmental enrichment improves outcome in experimental
      stroke.

PMID- 8571430
TI  - Aminoguanidine ameliorates and L-arginine worsens brain damage from intraluminal
      middle cerebral artery occlusion.
AB  - BACKGROUND AND PURPOSE: We studied whether the inducible nitric oxide synthase
      (iNOS) inhibitor aminoguanidine reduces focal cerebral ischemic damage in a
      relatively noninvasive stroke model in which the rat middle cerebral artery (MCA)
      is occluded using an intravascular filament. METHODS: In rats anesthetized with
      halothane, a nylon filament was advanced into the internal carotid artery until
      its tip occluded the origin of the MCA. The filament was left in place for 2
      hours and then withdrawn. Twenty-four hours later, rats received intraperitoneal
      injections of aminoguanidine (100 mg/kg BID; n = 7), aminoguanidine+L-arginine
      (300 mg/kg QID; n = 7), L-arginine alone (n = 6), D-arginine alone (n = 6), or
      vehicle (n = 10). Drugs were administered for 3 consecutive days. Infarct volume
      was determined by image analysis in thionin-stained brain sections 4 days after
      ischemia. iNOS mRNA was detected with the use of reverse transcription polymerase
      chain reaction. RESULTS: Cerebral ischemia led to iNOS mRNA expression in the
      affected brain 48 hours after induction of ischemia. Administration of
      aminoguanidine reduced neocortical infarct volume by 26% (P < .05 versus vehicle,
      ANOVA and Tukey's test), a reduction that was antagonized by coadministration of
      L-arginine (P > .05 versus vehicle). Administration of L-arginine alone, but not
      D-arginine, enlarged the infarct by 29% (P < .05). Aminoguanidine or L-arginine
      did not influence the increase in water content in the postischemic brain,
      indicating that the effect on infarct volume is not related to modulation of
      ischemic edema. CONCLUSIONS: These results demonstrate that cerebral ischemia is
      also associated with iNOS expression in a minimally invasive model of transient
      MCA occlusion and that iNOS inhibition reduces focal ischemic damage. The
      findings support the hypothesis that nitric oxide produced by iNOS contributes to
      ischemic brain damage and that inhibition of iNOS may be a valuable tool in the
      management of cerebral ischemia.

PMID- 8571432
TI  - Mitochondrial generation of reactive oxygen species after brain ischemia in the
      rat.
AB  - BACKGROUND AND PURPOSE: Brain mitochondria have a substantial capacity to
      generate reactive oxygen species after ischemia when the components of the
      respiratory chain are reduced and molecular oxygen is present. We tested the
      hypothesis that brain mitochondria in vivo produce reactive oxygen species after
      ischemia/reperfusion (IR) in rats at a rate sufficient to escape endogenous
      antioxidant defenses. METHODS: Ischemia-dependent production of hydroxyl radical
      in the hippocampus of the anesthetized rat was monitored with the use of
      intracerebral microdialysis. Transient global ischemia was produced by bilateral
      carotid artery occlusion and hemorrhagic hypotension to a mean arterial pressure
      of 35 mm Hg for 15 minutes followed by reperfusion for 60 minutes. Salicylic acid
      was infused into the hippocampus during the experiments, and changes in the
      recovery of its hydroxylated product, 2,3-dihydroxybenzoic acid (2,3-DHBA), were
      used to assess the effects of inhibitors of mitochondrial complex I on formation
      of hydroxyl radical during IR. Hydroxylation data from control groups of animals
      were compared with data from animals undergoing IR during treatment with either a
      mitochondrial complex I inhibitor alone or the inhibitor plus succinic acid.
      RESULTS: Transient ischemia led to a fivefold increase in the recovery of 2,3
      DHBA by microdialysis after 1 hour relative to control animals (P < .05).
      Inhibition of mitochondrial complex I prevented 2,3-DHBA formation after IR; this
      effect could be reversed by infusion of succinic acid by microdialysis during IR.
      CONCLUSIONS: The data indicate that reactive oxygen species generated by
      mitochondrial electron transport escape cellular antioxidant defenses and promote
      highly damaging hydroxyl radical activity after transient brain ischemia in the
      rat.

PMID- 8571433
TI  - Simplified model of krypton laser-induced thrombotic distal middle cerebral
      artery occlusion in spontaneously hypertensive rats.
AB  - BACKGROUND AND PURPOSE: The effects of thrombotic occlusion of the middle
      cerebral artery on compromised ischemic tissue may be different from and more
      severe than those of cerebral ischemia induced by mechanical occlusion of the
      artery. Photothrombosis, which is based on photochemical damage to the
      endothelium and subsequent platelet aggregation, is an efficient method to induce
      thrombosis in vivo. This study aimed to improve and simplify this unique method
      for an ischemia model of middle cerebral artery occlusion in rats. METHODS: Male
      spontaneously hypertensive rats (5 to 6 months old, 300 to 450 g) were
      anesthetized with halothane, endotracheally intubated, and mechanically
      ventilated. A krypton laser operating at 568 nm was used to irradiate the exposed
      distal middle cerebral artery with an intact dura above the rhinal fissure. The
      photosensitizing dye rose bengal (20 mg/kg body wt) was administered
      intravenously over 90 seconds starting simultaneously with 4 minutes of laser
      irradiation at a power of 20 mW to cause thrombotic occlusion of this artery.
      RESULTS: The irradiated middle cerebral artery was completely occluded by
      intraluminal thrombi within 3 minutes after simultaneous laser irradiation and
      rose bengal infusion. Thrombosed materials were not stained by phosphotungstic
      acid-hematoxylin stain (ie, aggregated platelets lacked apparent fibrin). The
      mean volume of 3-day-old infarction, indicated by the lack of staining with 2,3,5
      triphenyltetrazolium chloride, was 84.8 +/- 17.4 mm3 (mean +/- SD, n = 6).
      CONCLUSIONS: We demonstrated a reproducible and minimally traumatic model of
      brain infarction induced by the thrombotic distal middle cerebral artery
      occlusion in rats.

PMID- 8571434
TI  - Scoring systems for the differential diagnosis of ischemic and hemorrhagic
      stroke.

PMID- 8571435
TI  - Brain ischemia, mitochondrial cardiomyopathy, and rediscovering the wheel.

PMID- 8571436
TI  - Superior sagittal sinus thrombosis and acquired free protein S deficiency in the
      elderly.

PMID- 8571437
TI  - The prognosis of familial versus nonfamilial aneurysmal subarachnoid hemorrhage.

PMID- 8571438
TI  - Cerebral hyperperfusion antedates by years strokelike episodes in the MELAS
      syndrome.

PMID- 8571439
TI  - Protein kinase C activation during cerebral vasospasm.

PMID- 8571441
TI  - Women's socioeconomic position and contraceptive behavior in Togo.
AB  - Few studies have examined empirically the influence of women's position on
      contraceptive behavior in sub-Saharan Africa. Using data from the 1988 Togo
      Demographic and Health Survey, this article explores the linkages between various
      indicators of women's position and spousal communication about family planning
      and contraceptive use. The results highlight the importance to their
      contraceptive behavior of women's economic power and individual control over
      choice of partner. The likelihood of spousal communication about family planning
      and modern contraceptive use is significantly higher among women who exercised
      complete control over selection of partner than among those with arranged
      marriages. Women who work for cash are significantly more likely than those who
      do not to communicate with their spouses about family planning, particularly if
      they participate in rotating credit or savings schemes. Such participation also
      increases significantly the likelihood of ever using traditional and modern
      methods of contraception.

PMID- 8571440
TI  - Expanding access to emergency contraception in developing countries.
AB  - Emergency contraception has been called the best-kept contraceptive secret.
      Previous research shows that several regimens of postcoital contraception offer
      safe and effective ways for women to avoid pregnancy. Yet the methods are
      typically unavailable to women in developing countries. In this article, the
      authors review the main methods of emergency contraception and describe
      experience with them to date. The prevalence and urgency of the need for making
      these methods available to women in developing countries are assessed. The
      necessary elements for creating such access are described. In several developing
      countries, conditions for introducing the methods may be more favorable than in
      industrialized countries. These advantages are reviewed. Finally, the authors
      describe the challenges anticipated for broadening the availability of postcoital
      methods in the developing world. They conclude with a brief series of
      recommendations for policymakers.

PMID- 8571442
TI  - Determinants of induced abortion and their policy implications in four counties
      in north China.
AB  - A retrospective survey conducted in four counties in North China in 1991-92 shows
      that the probability of aborting a pregnancy is strongly related to parity. No
      induced abortions are found prior to the first live birth, and almost universal
      abortion is shown after the second. Women had a high risk of undergoing abortion
      after their first live birth because most (82 percent) had become pregnant again
      without meeting official requirements for late second births with long spacing
      between births. The likelihood that a pregnancy will be aborted is strongly
      determined by official family planning policy and regulations. Individual and
      household socioeconomic status plays a relatively insignificant role. Great
      variation in the prevalence of induced abortion exists at the county and village
      levels. In recent years, the incidence of induced abortion has increased among
      women with one living child. Even a two-child policy, with late childbearing and
      spacing, can have high social and health costs in a country where childbearing is
      universal and begins relatively early.

PMID- 8571444
TI  - Implementing the ICPD's message.

PMID- 8571443
TI  - Direct and judgmental measures of family planning program inputs.
AB  - This report compares two different approaches to measuring the strength of family
      planning programs in Bangladesh and Kenya. The first approach, the judgmental
      approach, has been used in a number of studies during the past two decades;
      scores on the characteristics of family planning programs are derived from the
      responses knowledgeable persons give to a series of questions. The second
      approach is to obtain direct measures of each item being considered. In
      Bangladesh, the total score varied trivially between the direct and the
      judgmental approaches. In Kenya, the total direct score was substantially higher
      than the judgmental score. The primary advantage of the judgmental approach is
      that comparative scores can be obtained for a larger number of countries for the
      same time period at a much lower cost than would be required by the direct
      approach.

PMID- 8571445
TI  - Bangladesh 1993-94: results from the Demographic and Health Survey.

PMID- 8571446
TI  - On the efficacy of withdrawal.

PMID- 8571447
TI  - The end in sight: terminating translation in eukaryotes.

PMID- 8571448
TI  - Cyclic AMP, the reluctant messenger in plants.
AB  - The possible role of cyclic AMP (cAMP) in plants has been an area of controversy
      for nearly 20 years: although cAMP and putative components of its synthesis,
      degradation and site of action can be demonstrated, there has been no clear
      identification of a signal transduction pathway dependent upon cAMP in plants.
      However, stronger evidence is accumulating for its possible role in stress
      signalling.

PMID- 8571449
TI  - Cooperativity: over the Hill.
AB  - Cooperativity, the ability of ligand binding at one site on a macromolecule to
      influence ligand binding at a different site on the same macromolecule, is a
      fascinating biological property that is often poorly explained in textbooks. The
      Hill coefficient is commonly used in biophysical studies of cooperative systems
      although it is not a quantitative measure of cooperativity. The free energy of
      interaction between binding sites (delta delta G) is a more stringent definition
      of cooperativity and provides a direct quantitative measure of how the binding of
      ligand at one site affects the ligand affinity of another site.

PMID- 8571450
TI  - The first prokaryotic lipocalins.

PMID- 8571451
TI  - Action at a distance: DNA-looping and initiation of transcription.
AB  - Effective initiation of transcription, especially in eukaryotes, requires the
      specific assembly of large protein complexes at promoters. We ask here how
      activator proteins that are bound hundreds or thousands of base pairs away from
      the promoter might facilitate this process if protein-protein interactions occur
      via looping of the intervening DNA. We show that the local concentration at the
      promoter of activator proteins bound at vicinal DNA sites can be substantially
      regulated by intrinsic or protein-induced distortion of the regular DNA
      conformation.

PMID- 8571452
TI  - The G-box: a ubiquitous regulatory DNA element in plants bound by the GBF family
      of bZIP proteins.
AB  - The G-box (CACGTG) is a ubiquitous, cis-acting DNA regulatory element found in
      plant genomes. Proteins known as G-box factors (GBFs) bind to G-boxes in a
      context-specific manner, mediating a wide variety of gene expression patterns. We
      suggest that, as for many biological systems, different combinations of these
      common elements can lead to diversity and specificity in the regulation of plant
      gene expression.

PMID- 8571453
TI  - Finding prospective partners in the library: the two-hybrid system and phage
      display find a match.
AB  - The two-hybrid system uses the efficacy of yeast genetic assays to identify
      protein-protein interactions. It permits the rapid cloning of genes encoding
      products that interact with a given protein of interest. Also being developed are
      phage display methods that allow direct physical selection of binding proteins.
      These methods have significantly altered strategies for analysing signaling and
      regulatory pathways.

PMID- 8571454
TI  - Transcriptional coactivators in yeast and beyond.
AB  - Coactivators are a novel class of transcriptional activator required at many
      eukaryotic promoters. Several coactivators have now been isolated, their
      identification often facilitated by genetic studies in yeast. Some of the
      proposed mechanisms of coactivator function may help explain synergy between
      transcriptional activators at eukaryotic promoters.

PMID- 8571455
TI  - Floaties in the gene pool.

PMID- 8571456
TI  - Maturation-promoting factor in the early days.

PMID- 8571457
TI  - [The organization of dispersed nucleolar chromatin and the ultrastructure of the
      nucleoli in the oogenesis of the common frog].
AB  - The structure of the nucleoli and their chromatin from grass frog Rana temporaria
      oocytes during different stages of oogenesis has been studied. Light microscopic
      analysis of dispersed according Callan's method (Callan et al., 1987) nucleoli of
      third stage of oogenesis (Dumont, 1972) revealed that by decreasing ionic
      strength to 25 mM spherical nucleoli got the appearance of necklace-like
      structures. Their electronmicroscopic analysis following by Miller's technique
      (Miller, Beatty, 1969) showed that they represent rosette-like structures which
      are connected to each other by ribosomal transcriptional units. Loops of the
      rosettes also are formed by transcriptional units of ribosomal genes. By the
      decreasing of transcriptional activity of nuclei from oocytes of 5-6th stages of
      oogenesis from hibernating frogs the structure of dispersed chromatin has been
      changed. The number of beads along the necklace-like structure axis decreased.
      Electron microscopic analysis of spread nucleolar chromatin from oocytes of these
      stages revealed the increase of part of inactive nucleosomal chromatin and the
      decrease of the number of loops in rosettes. The study of nucleoli ultrastructure
      showed that their morphology depends on their chromatin structure. In nucleoli
      with higher activity in oocytes of third stage of oogenesis fibrillar centers
      have not been found. At the same time in partially inactive nucleoli of 6th stage
      of oogenesis (Winter season) it was possible to identify well developed typical
      fibrillar centers. In those cases when nucleoli were completely inactive during
      the same stage of oogenesis and were not stained with 3H-actinomycin D, fibrillar
      centers were absent.

PMID- 8571458
TI  - [The lysosomal acid phosphatase activity of the peripheral blood neutrophils of
      women in the dynamics of the menstrual cycle].
AB  - During menstrual cycle of women, the intensity of fluorescence of acid
      phosphatase (IAF) was registered in lysosomes from peripheral blood neutrophils
      after staining with Acridin orange. It has been shown that such integral values
      as criterion of agreement (chi(2)) and information entropy by Shennon (h) are
      most informative values of IAF. It is suggested that the dynamics of chi-square
      and h in menstrual cycle reflects changes in enzymatic activity, and is
      associated with destroying the ovum utilizing the products of its lysis.

PMID- 8571459
TI  - [The functional-structural characteristics of the neurons in cultured explants of
      the cerebral cortex of rats subjected to immobilization-cold exposure in the
      prenatal developmental period].
AB  - A tissue culture was obtained from the sensorimotor cortex of rat embryos after
      keeping pregnant animals under immobilization-cold stress. The functional state
      of culture was determined by RNA synthesis intensity. On analysing the tissue
      morphology, much attention was paid to the pattern of cytoskeleton (microtubules
      and microfilaments) of neuronal processes. For both periods of cultivation (7 and
      14 days), the levels of RNA synthesis in culture of stressed animals were weaker
      than in the control one by 44 and 34%, resp. After 2 weeks of incubation the
      density of microtubules, i.e. the number of microtubules per process width, was
      reduced by 26% in profiles of dendrites. No changes in the number of
      microfilaments were detected. Besides, destruction of the neuron cytoplasm,
      redistribution of microtubules within dendrites, and reduction in the number of
      synaptic endings were noticed. All these alterations seem to be caused by
      lowering the capability of neurons to form their processes.

PMID- 8571460
TI  - The value of transvaginal color Doppler in the assessment of pelvic inflammatory
      disease.
AB  - This study compares transvaginal color and pulsed Doppler (TVCD), laparoscopic
      and clinical findings in 102 women with proven pelvic inflammatory disease (PID).
      Seventy-two (72) of them had acute symptoms, 11 presented with chronic pelvic
      pain and 19 patients were infertility cases suspected of tubal etiology. Uterine
      sonographic findings were demonstrated in 72 patients (70.6%). Free fluid in the
      cul-de-sac was demonstrated in 39 (38.2%) patients. Ovarian enlargement as the
      only finding was demonstrated in 6 (5.9%) patients, 22 (21.6%) presented with
      tubular adnexal structure, while in 74 (72.5%) patients it was of a complex
      nature. Color flow was obtained in all 6 patients presenting with ovarian
      enlargement, in 12 (54.5%) of those presenting with tubular adnexal structure,
      and in 56 (75.7%) of those with complex adnexal mass. Ovarian morphology was
      clearly delineated from adnexal mass in 59 patients (55.9%). The ipsilateral
      ovarian flow was altered in 50 of them (84.7%). The mean resistance index (RI) in
      patients with acute symptoms was 0.53 +/- 0.09 (+/-SD). It significantly differed
      from those obtained in patients with chronic pelvic pain (RI = 0.71 +/- 0.07) and
      infertility cases (RI = 0.73 +/- 0.09). We concluded that transvaginal color
      Doppler is useful additional tool in diagnosis and treatment monitoring in
      patients with PID.

PMID- 8571462
TI  - A novel ultrasonic technique for differentiating cysts from solid lesions:
      preliminary results in the breast.
AB  - The feasibility of a new ultrasonic technique to distinguish cysts from solid
      lesions is explored. High intensity pulses are used to induce acoustic streaming
      in cyst fluid, and this motion is detected using Doppler techniques. Acoustic
      streaming cannot be generated in solid lesions, therefore, its detection would
      indicate a cyst. In six of seven breast cysts motion was clearly generated and
      detected in vivo. Ultrasonic pulses with intensities up to 4.4 W cm-2 (I(spta) in
      water) were focused on the cysts for 10 s. Lesion diameters ranged from 0.6 to
      2.5 cm; induced flow velocities were less than 4.0 cm s-1.

PMID- 8571461
TI  - Assessment of fetal left cardiac isovolumic relaxation time in appropriate and
      small-for-gestational-age fetuses.
AB  - Left ventricular isovolumic relaxation time was studied in 22 appropriate-for
      gestational-age fetuses (AGA, 26-40 wk) and 12 small-for-gestational-age fetuses
      (SGA, 29-37 wk). Left ventricular isovolumic relaxation time was determined from
      the interval between aortic valve closure and maximal left atrial dimension by M
      mode, and from the interval between aortic valve closure artefact and onset of
      transmitral flow by pulsed Doppler. Mean left ventricular isovolumic relaxation
      time by M-mode (36 +/- 6 ms) and by pulsed Doppler (49 +/- 10 ms) were
      significantly different (p < 0.05) in AGA while this was not so in SGA (56 +/- 10
      ms vs. 60 +/- 8 ms). A significant difference (p < 0.05) in mean left ventricular
      isovolumic relaxation time by M-mode existed between AGA (36 +/- 6 ms) and SGA
      (56 +/- 10 ms), whereas this was not so for pulsed Doppler (48 +/- 10 ms vs. 60
      +/- 8 ms). Mean left ventricular isovolumic relaxation time by Doppler was
      significantly larger (mean difference 14 +/- 8 ms; p < 0.05) than by M-mode in
      AGA. However, there was no difference in mean left ventricular isovolumic
      relaxation time between the two ultrasound modalities in SGA. These data suggest
      synchronization of mitral cusp separation and transmitral blood flow in the SGA
      fetus. We speculate that, in the SGA fetus, delayed left ventricular isovolumic
      relaxation time may reflect cardiac diastolic dysfunction.

PMID- 8571463
TI  - Is there a hemispheric side preference of cardiac valvular emboli?
AB  - Microaggregates arising from prosthetic cardiac valves offer the opportunity to
      examine the distribution of valvular emboli in the human cerebral circulation.
      Forty-four patients with different kinds of prosthetic valves underwent bilateral
      transcranial Doppler monitoring for 1 h to detect high intensity Doppler signals
      representing microemboli. Comparing the total number of embolic signals in both
      middle cerebral arteries (N = 1066), a side preference was not statistically
      evident. However, clear side preferences were obvious in some individuals. The
      lack of statistical evidence for hemispherical preferences of cardiac
      microembolism in general does not exclude selective streaming in individuals,
      explaining the clinical observation of lodging preferences of recurrent cardiac
      embolism. A cardiac source of microembolism may mimic disease activity of
      extracranial carotid artery stenosis and bias the localization of embolic source.

PMID- 8571464
TI  - Acoustic generation of intra-arterial contrast boluses.
AB  - Microbubbles generated by ultrasonic cavitation in vivo might be useable as flow
      indicators in some situations instead of injectable contrast agents. Knowledge of
      those vascular microbubble-generating ultrasonic fields which produce from
      negligible up to significant damage will help improve guidelines for more
      effective, safer diagnostic and therapeutic ultrasound. Microbubble boluses have
      been generated by a 1.8-MHz, focused sound field in the in vivo canine abdominal
      aorta. Spatial peak acoustic intensities of 19,000 W cm-2 generated microbubble
      boluses when exposure was longer than 12 ms, whereas intensities greater than
      4300 W cm-2 generated a bolus when exposure was for 250 ms. The onset time of
      these boluses (less than one cardiac cycle) is unachievable with intravenous
      contrast injection. With optimized waveforms and focusing, acoustic bolus
      generation may prove to be an effective, minimally invasive method for fast
      performance of certain selective angiography.

PMID- 8571465
TI  - Registration of three-dimensional compound ultrasound scans of the breast for
      refraction and motion correction.
AB  - Use of multiple look directions, that is, compound imaging, has been shown
      previously to increase detection of specular reflectors and averaging of speckle
      noise in gray-scale images, often at the expense of spatial resolution and other
      misregistration errors. In color flow imaging, additional view angles can fill in
      vessels missed due to Doppler angle dropout and increase quantitative and visual
      Doppler accuracy by triangulation or a simple peak-frequency-shift combination
      algorithm. Image registration and unwarping throughout multiple three-dimensional
      (3D) volume sets should correct for many refraction artifacts, motion between and
      during compounded image sets and even, possibly, positioning errors between image
      sets, acquired months apart, to display growth of abnormalities. The registration
      described here does not provide sufficient accuracy for formation of enhanced
      coherent apertures, but shows promise in some cases to provide superior compound
      images and possibly comparisons of current and prior studies. In this study, the
      breast is stabilized by mild compression between a flat plate and a scanning
      membrane. Registration and unwarping is performed retrospectively on two separate
      volumetric data sets by defining pairs of corresponding points and, in some
      cases, line and plane segments. Three-dimensional linear affine transforms are
      performed using identified points, lines and planes. 3D nonlinear warped
      transforms are also possible given adequate numbers of identifiable points. More
      than two data sets are registered by selecting one as the standard, and
      registering the remainder to match. The most appropriate algorithm, such as
      averaging or maximum amplitude, may be used to combine the data sets for display.
      Significant success has been achieved in compound display of a test object and of
      the breast in vivo, even when there was relative motion or warping between image
      sets. In pulse-echo imaging, homologous feature registration for compounding
      appears to have advantages over mechanically registered compounding methods
      previously employed in the breast and significant increases in lesion and
      structural conspicuity are noted due to a reduction in speckle noise. The
      improvements from compounding in 3D, surface-rendered Doppler imaging of
      vasculature are striking.

PMID- 8571466
TI  - Effects of nonuniform insonation by catheter-tipped Doppler transducers on
      velocity estimation.
AB  - Studies of the coronary arteries using intravascular Doppler catheters have
      frequently been performed to assess the local circulation in various clinical
      situations. The parameters which are correlated with clinical observations are
      usually calculated from the intensity weighted mean velocity (IWMV) or the
      maximum velocity extracted from the Doppler power spectrum. It is known that
      these estimates are affected by nonuniform insonation of the blood vessel by the
      ultrasonic beam. The sample volume of a commercially available Doppler catheter
      has been theoretically and experimentally studied, and the effects of the
      nonuniform sampling of the vessel by the ultrasound beam examined. The results
      show that the velocity estimates are dramatically affected by both the position
      of the catheter within the artery, and the blood velocity profile. It is
      concluded that the maximum velocity estimator is more reliable than the IWMV
      estimator, but that results obtained with this estimator must also be treated
      with extreme caution.

PMID- 8571467
TI  - Adaptive SVD-based AR model order determination for time-frequency analysis of
      Doppler ultrasound signals.
AB  - The short-time Fourier transform provides a picture of the spectral components
      temporal location in time-varying signals, but its performance is limited by the
      intrinsic trade-off between time and frequency resolutions. In the present study,
      this problem is addressed using a spectral estimator based on a combination of
      the autoregressive (AR) modeling technique and a new automatic model order
      selection method. The order estimation is achieved by means of the singular value
      decomposition (SVD) of an appropriate data matrix in conjunction with a new
      criterion (dynamic mean evaluation, DME). The latter is used to decide which
      singular values correspond to the signal and which to the noise subspaces,
      avoiding an a priori threshold definition, thus giving the variable AR model
      order on consecutive short-time segments. Combination of the AR high frequency
      resolution capabilities and the SVD plus DME robustness and simplicity make the
      overall method reliable in many practical applications, mainly in the analysis of
      time-varying signals corrupted by noise. The proposed procedure has been applied
      to benchmark as well as to Doppler signal analysis. Some examples are reported
      confirming the above-mentioned properties.

PMID- 8571468
TI  - Quantitative investigation of in vitro flow using three-dimensional colour
      Doppler ultrasound.
AB  - A quantitative in vitro flow study was performed by using a three-dimensional
      colour Doppler imaging system. This system was based on a clinical ultrasound
      instrument with its transducer mounted on a motor-driven translation stage. A
      vascular and tissue-mimicking phantom containing two wall-less vessels, one
      normal and another stenotic, was used to quantify the measurement accuracy of the
      flow velocity and the flow field. Steady state flows, having Reynolds numbers
      ranging between 460 and 1300, were generated by a computer-controlled positive
      displacement pump. Effects of the parameter settings of the ultrasound instrument
      on results of the estimation of flow field were also studied. Experimental
      results show that our three-dimensional colour Doppler system's velocity accuracy
      was better than 7% of the Nyquist velocity and its spatial accuracy was better
      than 0.5 mm. The system showed a good correlation (r = 0.999) between the
      estimated and the true mean flow velocity, and a good correlation (r = 0.998)
      between the estimated maximum and the true mean flow velocity. This study is our
      first step toward validating the measurement of the three-dimensional velocity
      and wall shear stress distributions by using three-dimensional colour Doppler
      ultrasound

PMID- 8571469
TI  - Ultrasound backscatter at 30 MHz from human blood: influence of rouleau size
      affected by blood modification and shear rate.
AB  - High frequency intravascular ultrasound may show a high intensity backscatter
      from blood which hampers the discrimination between lumen and arterial wall. In
      this study, the acoustic behaviour of blood at 30 MHz in relation to rouleau size
      was analyzed. In a Couette viscometer, high frequency (20-40 MHz) backscatter
      data from normal and modified blood samples from eight volunteers were obtained
      at shear rates from 0 to 1000 s-1. The acoustic behaviour of blood was quantified
      by the integrated backscatter power and the spectral slope of the backscatter
      coefficient. Backscatter from blood depended on rouleau size. At a shear rate of
      zero, both whole blood and rouleau-enhanced blood showed a 11-dB-higher
      integrated backscatter power than rouleau-suppressed blood, which itself was 10
      dB higher than that of hemolysed blood, the latter showing a 6-dB-higher
      backscatter than saline. Platelets did not contribute to the backscatter power.
      Plasma and saline produced no detectable integrated backscatter power other than
      noise. The spectral slope of whole and rouleau-enhanced blood was small (1 and
      0.5, respectively), whereas rouleau-suppressed blood and hemolysed blood (both
      with a slope of 3.3) behaved almost like a Rayleigh scattering medium (slope =
      4). The backscatter from rouleau-suppressed blood showed no shear rate
      dependence. At low shear rates ( < 0.8 s-1 for integrated backscatter power and <
      0.2 s-1 for the spectral slope), whole blood and rouleau-enhanced blood tended to
      the results from the static situation (no shear). At high shear rates ( > 80 s-1
      for integrated backscatter power and >11 s-1 for spectral slope), these samples
      tended to the results of rouleau-suppressed blood. Ultrasound backscatter at 30
      MHz from human blood is only caused by red blood cells. With increasing aggregate
      (rouleau) size, the integrated backscatter power increased by 11 dB, and the
      spectral slope decreased from 3.3 to 1.

PMID- 8571470
TI  - Roles of hematocrit and fibrinogen in red cell aggregation determined by
      ultrasonic scattering properties.
AB  - Parameters of the power spectrum of backscattered echoes were applied to
      quantitatively evaluate red cell aggregation in vitro. Human red cell suspensions
      were circulated in a closed loop of tubing, and ultrasonic, radiofrequency, echo
      signal data were obtained using a 10-MHz transducer. Data acquisition was
      performed at 30-s to 1-min intervals for 5 min after flow stoppage. Two
      parameters of the normalized power spectrum of the echo signals, spectral slope
      and Y-intercept, were computed, and estimates of two scattering properties, the
      scatterer size and acoustic concentration were calculated from these parameters
      using equations based on scattering theory. Size and acoustic concentration were
      observed as they changed over time after the stoppage of flow. The key findings
      were that hematocrit affected the rate of cell aggregation while fibrinogen
      controlled aggregate size and acoustic concentration.

PMID- 8571471
TI  - Pro- and antifibrinolytic effects of ultrasound on streptokinase-induced
      thrombolysis.
AB  - We have earlier documented that ultrasound can enhance the fibrinolytic effect of
      streptokinase and shorten the reperfusion time under experimental conditions. The
      present study concerns the magnitude of the effect in relation to ultrasound
      frequency, intensity and exposure time. The effect of ultrasound on the
      structural properties of the fibrin network was evaluated by scanning electron
      microscopy. Whole blood clots were created and exposed to streptokinase (5000
      U/mL). In paired experiments, one clot was also exposed to pulsed ultrasound.
      Lysis is expressed as the percentage decrease in clot weight. Clot lysis was
      equally affected by ultrasound in the range of 0.5 to 2.3 MHz. Below 0.5 W/cm2 no
      enhancing effect was observed, while intensities between 0.5 and 1.5 W/cm2
      resulted in a significant enhancement of clot lysis. Intensities above 4 W/cm2
      inhibited the fibrinolytic effect of streptokinase but not of rt-PA. From
      scanning electron microscopy there was no evidence that ultrasound disrupted the
      clot surface or damaged the fibrin structure.

PMID- 8571472
TI  - Comet assay reveals DNA strand breaks induced by ultrasonic cavitation in vitro.
AB  - The induction of DNA strand breaks in cultured Chinese hamster ovary (CHO) cells
      was investigated in suspensions directly exposed to 2.17-MHz ultrasound.
      Production of hydrogen peroxide, a DNA-damaging sonochemical, by inertial
      cavitation was enhanced by the use of argon-and-oxygen-bubbled media and cell
      survival was improved by establishing standing waves and minimizing tube
      rotation. Viable cells were separated from the suspension after exposure and kept
      on ice for evaluation with the single-cell gel electrophoresis (comet) assay.
      With this assay, DNA damage from as little as 2-mumol/L hydrogen peroxide
      treatment for 30 min could be detected, and cell survival as low as 2-5% after
      ultrasound exposure was adequate for assay. An ultrasound dose-response trend was
      noted for increasing pressure amplitude up to 0.82 MPa (free field) and
      increasing exposure duration up to 4 min. The cells were able to repair some of
      the strand breaks when warmed to 28 degrees C for 30 min. The effect was not
      eliminated by addition of catalase, which indicates that the DNA damage was not
      due to the action of residual H2O2 alone. The results confirm the hypothesis of
      DNA damage in cells surviving inertial cavitation.

PMID- 8571473
TI  - [The detection of latent circulatory and respiratory failure in urologic patients
      at the prehospital stage].
AB  - Elderly patients admitted to urological hospitals and departments with increasing
      frequency have the disease complicated with age-specific and associated
      circulatory and respiratory affections. Occasionally, these complications are not
      clinically evident, but may acquire unwanted decompensated course. Subclinical
      forms of circulatory and respiratory insufficiency can be managed using
      relatively simple methods of functional assessment applicable in outpatient
      setting. Recommendations are provided on operative preparations which can be made
      at home or in outpatient department thus reducing the cost of hospital stay.

PMID- 8571474
TI  - [The efficacy of bacteriophage preparations in treating inflammatory urologic
      diseases].
AB  - Urinary infection is the most commonly encountered hospital infection.
      Antibacterial therapy promotes selection and dissemination of polyresistant
      microorganism strains, development of intestinal dysbacteriosis, reduction of
      intestinal contamination resistance. Clinical and bacteriological efficacy of
      urinary infection treatment with bacteriophage preparations (pyocyanic, proteus,
      staphylococcal, coliphage, combined pyobacteriophage) was studied. Sensitivity of
      the infective agent phage isolated from urological patients was tested before
      treatment. The preparations were adapted to recently isolated agents from
      urological patients to raise phage sensitivity of the strains. A total of 293
      strains were studied. Phage sensitivity made up 68.9%. Bacteriophage preparations
      were used both locally and orally in 46 patients with acute and chronic
      urogenital inflammation. Bacteriological efficacy amounted to 84%, clinical one
      to 92%. It is inferred that phagotherapy is effective and safe therapeutic
      modality in the treatment of urinary infection in monotherapy and in combination
      with antibiotics.

PMID- 8571475
TI  - [The use of cephmetazon in treating infectious inflammatory diseases of the upper
      and lower urinary tract].
AB  - A clinical trial of cephmethasone (Sankyo, Japan) has been performed in 40
      patients with pyelonephritis. 3 patients with chronic cystitis. 19 patients with
      chronic prostatitis. Cephmethasone, cephalosporin of the second generation, is
      active against gram-positive and gram-negative agents, hospital infection. The
      treatment course consists of 4-14 daily doses of 2-4 g. Bacterial elimination was
      reached in 79.5% of the cases with a complete response in 70% and partial one in
      30% of patients. Side effects were not registered. As a highly active wide
      spectrum antibiotic, cephmethasone is offered for treatment of urinary
      infections. Cephmethasone monotherapy provides a rapid relief of cystitis,
      prostatitis and pyelonephritis symptoms.

PMID- 8571476
TI  - [Phytoperfusion of the bladder after adenomectomy].
AB  - For continuous irrigation of the bladder after prostatic adenomectomy herb
      infusion (Urtica dioica L. 12-15 g/l, Hypericum perforatum L. 8-12 g/l.
      Marticaria recutita L. 8-10 g/l, folia Plantaginis majoris 7-10 g/l, Herba
      Millefolii 4-6 g/l, folia Betula 3-5 g/l. Artemisia vulgaris L. 1-2 g/l, folia
      Fragaria vesca 3-4 g/l, water 11 maximum) was dripped through a thin suprapubic
      and urethral drainages. Such phytoperfusion of the urinary bladder used in 22
      patients reduced postoperative blood loss, bacteriuria, prevented hemorrhagic and
      purulent inflammation following adenomectomy. Side systemic effects were not
      reported.

PMID- 8571477
TI  - [Ciprofloxacin in the treatment of chronic bacterial prostatitis].
AB  - 17 exacerbation and 13 latent CBP cases received ciprofloxacin in a dose 500 mg
      twice a day orally for 6-34 days. At pretreatment microbiological investigation
      of the prostatic juice 49 cultures of 7 microorganism species were isolated (12
      cases of monoculture, 18 cases of 2-component associations). S. epidermidis and
      E. faecalis occurred more frequently (in 29.4 and 25%, respectively).
      Ciprofloxacin was highly active against all the isolated agents and by the number
      of sensitive to it strains proved superior to control antimicrobial drugs. Good
      and satisfactory treatment outcomes were achieved in 76.8% of patients. Side
      effects recorded in 8 patients (26.6%) caused the drug undue discontinuation in 1
      patient only.

PMID- 8571478
TI  - [The preliminary results of a study of the role of endogenous nitric oxide in
      pregnant women with chronic glomerulonephritis, hypertension and puerperal
      eclampsia].
AB  - NO-synthase activity and formation of ERP/NO were evaluated in 19 pregnant women
      by high activity of platelet guanylate-cyclase (GC) and presence of z-arginine.
      The examinees were divided into 4 groups: 3 women with chronic glomerulonephritis
      (CGN), 9 patients with essential hypertension (EH), 3 nonpregnant women of
      reproductive age with EH, 3 healthy pregnant women. One patient had puerperal
      eclampsia. Z-arginine activation failed to change GC activity in healthy pregnant
      women, reduced it in pregnant and nonpregnant women with EH, increased GC
      activity 1.6-fold in a patient with puerperal eclampsia and in CGN pregnant
      females. It is inferred that changes in NO-dependent synthesis of cGMP manifested
      more distinctly in a patient with puerperal eclampsia.

PMID- 8571479
TI  - [Changes in the picture of chronic diseases on long-term hemodialysis treatment].
AB  - New data published in the literature provided evidence for appearance of an
      unknown variant of amyloidosis recorded in patients with a 5-15-year history of
      hemodialysis. Such amyloidosis may result from high blood levels of beta-2
      microglobulin unremovable at standard hemodialysis. Even highly permeable
      membranes which permit beta-2-microglobulin penetration fail to produce negative
      balance of this metabolite as the procedure stimulates leukocyte activity and,
      consequently, beta-2-microglobulin production. In spite of the fact that contact
      of the blood with synthetic materials during hemodialysis is not longer than 3-5
      hours, blood elements and endothelial cell metabolism, homeostasis undergo
      serious alterations. These effects of biocompatibility provoke the condition of
      enhanced activation similar to chronic inflammation. Thus, we deal with a new
      phenomenon in the field of hemodialysis. The efforts of investigators should be
      aimed at studying long-term adaptation of the body which rings atypical picture
      of chronic diseases.

PMID- 8571480
TI  - [The treatment of patients with benign prostatic hyperplasia with Proscar MSD
      (finasteride)].
AB  - 53 patients have undergone 1-year conservative treatment of benign prostatic
      hyperplasia with the drug proskar MSD. All the patients had the disease stage I
      II, maximal urination rate at least 5 ml/s, residual urine to a maximum 150 ml.
      Benign nature of the disease was confirmed by the test with prostate-specific
      antigen. Selection of patients, follow-up and assessment of treatment results
      were conducted according to the scale of the International System of Overall
      Assessment of Prostatic Lesions. Proskar MSD was found active in benign prostatic
      hyperplasia basing on the shifts in the main three indices (symptom status,
      maximal urination rate, prostate size).

PMID- 8571481
TI  - [Extracorporeal lithotripsy in the treatment of urolithiasis].
AB  - The material gained in the urological clinic of the Moscow Regional Research
      Clinical Institute covers 2000 cases of uroliths treated with extracorporeal
      lithotripsy (ECL) for 4 years. Factors implicated in the treatment outcomes,
      measures to prevent ECL complications, recommendations for ECL regimens in
      different clinical forms are specified.

PMID- 8571482
TI  - [The ultrasonic diagnosis and treatment of benign kidney tumors].
AB  - Literature data and first-hand experience with 31 patients having benign renal
      tumors support high diagnostic efficacy of ultrasound scanning (USS) in this
      disease. USS reveals angiomyolipomas the typical picture of which permits
      ultrasound monitoring thereof. However, USS appearance of renal adenoma is
      similar to that of renal cancer. In view of frequent malignant transformation of
      renal adenoma, nephrectomy is thought valid in renal adenoma patients.

PMID- 8571483
TI  - [An experimental study of the antitumor activity of preparations in a model of
      prostatic cancer].
AB  - A trial of a newly developed experimental model of prostatic cancer showed its
      convenience in simulating clinical symptoms and response to treatment. The model
      is effective in the studies of anticancer drugs with various mechanisms of action
      with special emphasis on immunomodulators as a promising adjuvant modality.

PMID- 8571485
TI  - [A detubularized reservoir for the urine made from the small intestine].
AB  - In the department of urology of the Georgian Cancer Research Center creation of
      small intestinal detubularized reservoir for urine was practiced for 4 years
      (1990-1994). Of a total of 35 patients, 27 underwent cystectomy for bladder
      cancer, whereas 8 patients with secondary cancer of the bladder and rectum were
      subjected to exenteration of the small pelvis organs. In 29 patients the
      reservoir was made using invagination valvular mechanism (in 6 cases according to
      D. Skinner, in 23 according to an original technique). Non-invagination valvular
      device according to the authors' technique was used in the other 6 patients
      (group 3). In postoperative period 3 patients died. A mean follow-up lasted 18
      months. With time, the reservoir volume increased with a parallel fall in
      pressure. Anatomical conditions of the kidneys compared to the baseline
      conditions have improved, reflux pyelonephritis was absent. Adequate valvular
      function recovered in group 3. Rejection of invagination valves diminishes the
      duration of the surgery, makes the operative procedure easier. Introduction of
      the original non-invagination valvular device proves to reliable sealing and easy
      catheterization of the reservoir.

PMID- 8571486
TI  - [An algorithm for the ultrasonic monitoring of patients who have undergone
      cystectomy].

PMID- 8571484
TI  - [Our experience in treating patients with surface cancer of the bladder].
AB  - 210 patients with surface cancer of the bladder were divided into three groups.
      67 patients of group 1 underwent transurethral resection of the bladder (TRB)
      followed by preventive intravesical chemotherapy. 91 patients of group 2 received
      preventive intravesical BCG after TRB. 61 control patients (group 3) had TRB
      only. Recurrences emerged in 15 (16.5%), 12 (62.7%) and 45 (73.8%) group 2, 1 and
      3 patients, respectively. The preventive chemotherapy was effective only in
      patients with primary tumor (the recurrence rate 42.3%), the relapses being less
      responsive to it (the recurrence rate 75.6%).

PMID- 8571487
TI  - [The indications for a transvesical approach in the surgical treatment of
      vesicovaginal fistulae].
AB  - Basing on 139 cases with vesicovaginal fistulas treated, the authors review
      diagnostic and clinical aspects of these fistulas, the performance of
      fistuloplasty via transvesical approach. Clear indications for fistuloplasty via
      transvesical approach have been formulated.

PMID- 8571488
TI  - [Posttuberculous cystalgia].
AB  - Follow-up outcomes of urogenital tuberculosis with involvement of the bladder are
      provided for patients of the Novosibirsk regional and city hospitals. The cure
      was achieved in 42.1% of patients, posttuberculous cystalgia (PTC) developed in
      36.8% microcystitis in 21.1% of cases. Age-related hormonal insufficiency
      contributes to the onset of PTC. An original technique of laser thermopuncture is
      detailed.

PMID- 8571489
TI  - [The complications of endo-corpora cavernosa prosthesis].

PMID- 8571490
TI  - [New developments in the treatment of erectile impotence].

PMID- 8571491
TI  - [The etiological and pathogenetic bases of nephrolithiasis].
AB  - A new outlook on etiology and pathogenesis of nephrolithiasis regards renal
      tubular acidosis (RTA) as the basic pathogenetic factor of nephrolithiasis. These
      conclusions were made basing on the findings on blood and urine glycolysis
      enzymes, lactic acid, acid-base metabolism, titrated acids, ammonium. RTA stages
      responsible for the variety of the forming concrement and two groups of
      nephrolithiasis etiological factors (acting on epithelial cell of the nephron and
      involved in urinary processes) are distinguished.

PMID- 8571492
TI  - [Lipid peroxidation in the kidney tissue of patients with nephrolithiasis and
      chronic pyelonephritis].
AB  - Lipid peroxidation (LPO) activity has been analyzed in homogenates and microsomes
      of cortical samples obtained intraoperatively from the kidneys of 33 patients. Of
      them, 21 patients had mild, moderate or severe pyelonephritis or nephrolithiasis.
      Unaffected cortical tissue from renal carcinoma patients was used as control. LPO
      activity was judged by basal level of malonic dialdehyde (MDA) and MDA growth in
      the homogenate and microsomes following initiation of ascorbate-dependent LPO.
      Activation of LPO was registered in patients with moderate disease with active
      inflammation. They also exhibited greater MDA basal levels and rapid MDA increase
      in response to in vitro initiation of ascorbate-dependent LPO simultaneously with
      attenuation of endogenous antioxidant defense. In severe pyelonephritis and
      nephrolithiasis with drastic deficiency of renal function LPO activity was low
      and nonresponsive to stimulation either by ascorbate or Fe+2. This is probably
      due to lack of the substrate after massive death of renal cells. Enhancement of
      LPO activity in patients with pyelonephritis or nephrolithiasis against
      functioning kidneys may appear responsible for destruction of renal tissue.

PMID- 8571493
TI  - [On the way to unattainable medicine].

PMID- 8571494
TI  - [Modern examination methods in pneumology].
AB  - In addition to qualitative establishment of diagnosis the aim of modern
      investigational procedures is quantitative analysis of disease extension and of
      functional impairment. The most important endoscopic-bioptical techniques for
      establishment of diagnosis are bronchoscopy and thoracoscopy. In bronchology
      flexible bronchoscopy with a relative share of about 90% clearly holds now a
      dominant position versus the rigid technique. Suspected cancer is the most
      prominent indication (ca. 60%). Visible intrabronchial lesions can be diagnosed
      in more than 90%. In extrabronchial and peripheral bronchopulmonary disease
      technical aids like transbronchial needle aspiration (TBNA), bronchoalveolar
      lavage (BAL) or transbronchial biopsy (TBB) are required, resulting in a
      diagnostic yield, that may range between 30 and 90% depending on the particular
      disease entity. Thoracoscopy is the second most important endoscopic procedure
      and accounts for about 1/10 of the investigational frequency of bronchoscopy.
      Pleural - generally exsudative - effusion provides by far the most frequent
      indication with a relative incidence of 75%. Etiological diagnosis can be
      established in about 90% of pleural effusions. The maximum yield of 100% may be
      achieved in tuberculous effusions, in malignant effusion sensitivity comes close
      to 100%. Non-endoscopic bioptical techniques include guided perthoracic needle
      aspiration and "blind" pleural biopsy. Diagnostic escalation or tumor staging may
      require surgical procedures, which can be performed by conventional techniques
      (mediastinoscopy, minithoracotomy) or video-assisted thorascopy. Explorative
      thoracotomy is the most extensive investigation. For functional evaluation of
      number of "classical" techniques are available (spirometry, gas transfer
      analysis, spiroergometry) more recently expanded by radionuclide perfusion and
      ventilation studies. Besides grading of functional impairment they allow clinical
      diagnosis of diseases characterized by specific functional patterns (asthma,
      bronchitis, emphysema, sleep associated disorders) and serve preoperative
      assessment in surgery. Increasingly important modern imaging techniques like
      computed tomography (CT), nuclear magnetic resonance (NMR) or ultrasonic
      investigation are not featured in this clinically focused article.

PMID- 8571495
TI  - [Pulmonary emphysema--lung transplantation].
AB  - The most frequent form of lung emphysema leading to respiratory failure is the
      tobacco bronchitis-induced type of emphysema the so called chronic obstructive
      pulmonary (lung) disease (COPD). Histologically the centrilobular or centriacinar
      emphysema is believed to develop due to elastase and oxidant overload with
      concomitant antiprotease deficiency. The alpha1-antitrypsin deficiency is a rare
      genetic defect leading also in non-smoking patients to early death due to
      panlobular or panacinar emphysema. The functional pattern of both emphysema types
      shows irreversible lung overinflation with severe mainly expiratory bronchial
      obstruction with various degrees of pulmonary hypertension alpha1
      proteinaseNinhibitor deficiency emphysema is prophylactically treated with
      prolastine and if hypoxia (PaO2 > 55 mm/Hg) is present with long term oxygen
      therapy. If hypercapnia develops O2 Therapy is combined with non invasive
      pressure supported ventilation. Volume reducing surgery may precede. In
      nonsmoking emphysema patients long term oxygen therapy and later unilateral lung
      transplantation improves quality of life as well as life expectancy.

PMID- 8571496
TI  - [Lung embolism as the cause of death in legal medicine].
AB  - In 16,216 autopsies 381 cases (2.35%) of pulmonary embolism were found to be the
      immediate cause of death. 53.8% of the cases were due to natural reasons and
      44.6% were due to violence (preferably accidents followed by immobilisation). 149
      persons died within the first three weeks of illness. In 63 cases the source of
      embolism could not be found. The frequency of pulmonary embolism in this study
      complies with other extensive researches. The practical and legal relevance of
      death caused by pulmonary embolism (kind of death, cause, sudden death,
      statistics of mortality, certainty of the diagnosis, medical postmortem
      examination, order of autopsy) are discussed.

PMID- 8571497
TI  - [Clinical studies of the incidence of pulmonary and extrapulmonary tuberculosis].
AB  - On the whole 797 patients (mean age 49.5 +/- 18.6 years) with tuberculosis who
      were hospitalized during 1987 and the first half of the year 1994 were
      investigated. 148 (18.6%) of these patients were foreigners. Regarding the age,
      the patients of German origin were mostly above 40 years (70.5%). Within the
      group of foreigners, 61.5% were below 40 years. 83.3% of the patients suffered
      from pulmonary and 11.4% from extrapulmonary and 11.4% from extrapulmonary
      tuberculosis. 5.3% of these patients had both manifestations. The tuberculin tine
      test was positive in 95.7% and negative in 4.3%. In 63.9% of all patients the
      tuberculosis was localized in the upper lobe of the lung. The tuberculosis was
      established bacteriologically in 56.0% and histologically in 16.5%. Both methods
      were applied in 13.6%. The tuberculosis was deteriorated by chronic alcoholism.
      Malignant diseases were recorded in 17 (2.1%) of the patients. 22 (2.8%) died
      during their stay at the hospital.

PMID- 8571498
TI  - [Therapy and prognosis of tuberculosis].
AB  - Treatment and prognosis of tuberculosis. Worldwide the so-called short-course
      chemotherapy has become the standard treatment for tuberculosis. The 6-month
      regimen consists of isoniazid, rifampin, and pyrazinamid given for 2 month
      followed by isoniazid and rifampin for 4 month. Ethambutol or streptomycin is
      added in the first 2 month in patients with advanced disease. This recommendation
      applies to both HIV-infected and uninfected persons. The major determinant of the
      outcome of treatment is patient adherence to the drug regimen. In susceptible
      strains the success rate with the 6-month regimen in sputum conversion is far
      beyond 90% within the first two month of therapy. The relapse rate after 3 to 5
      years is about 0-3%. Multiple-drug-resistant tuberculosis (i.e., resistance to at
      least two drugs) presents difficult treatment problems. Treatment must be
      individualized and based on susceptibility studies. For patients with
      tuberculosis that is resistant to rifampin and isoniazid, even the best available
      treatment is often unsuccessful. The role of new agents such as the quinolone
      derivatives and amikacin in the treatment of multidrug-resistant disease is not
      known, although these drugs are commonly being used in such cases.

PMID- 8571499
TI  - [Prognosis of sarcoidosis].
AB  - Sarcoidosis is a frequent, systemic, granulomatous disorder with predominant
      involvement of the hilar lymph nodes and the pulmonary parenchyma. By
      bronchoalveolar lavage an activation of alveolar immune cells has been observed
      yielding a detailed concept of the immunopathogenesis of the disease from which
      new, clinically applicable staging parameters are delineated. There is some
      evidence that immunopathogenetic mechanisms determine the course and the
      prognosis of the disease.

PMID- 8571500
TI  - [Sarcoidosis. Dependence of life expectancy on lung function, respiratory
      symptoms, roentgenologic stage and age at diagnosis and significance of
      extrapulmonary manifestations].
AB  - Patients with intrathoracic sarcoidosis have - during prolonged observation (27
      years) - the same survival as the general population. A higher mortality from
      sarcoidosis as well as from diseases not related to sarcoidosis is found among
      persons who at the time of diagnosis of sarcoidosis had respiratory symptoms and
      a low FEV1, TLC and Tiffeneau. Our knowledge of the prognosis for extrapulmonary
      manifestations and their influence on survival is sporadic. Symptoms from heart
      and CNS have in studies of selected patients been connected with an elevated
      mortality.

PMID- 8571501
TI  - [Alternative medicine in private personal insurance].
AB  - In Germany there is a trend to so-called "natural" or "alternative" medical
      methods especially among young people of good education and higher income. Those
      persons are also the typical target group of the private person insurance so that
      it seems necessary to deal with such methods. While the original "classical"
      methods of naturopathy have been acknowledged in the scientific medicine for many
      years and are mainly used in the medical rehabilitation, the so-called
      "alternative" methods are further on controversial. In the first place, the risks
      of such unconventional methods are to be monitored, especially the danger of a
      wrong diagnosis in using unproved diagnostical methods and the danger of side
      effects in therapy. Another problematical fact is that during an unconventional
      treatment the diagnosis of an intoxication by outdoor or indoor pollution or by
      amalgam of toothfillings is often made without standing a critical proof.
      Usually, an expensive therapy will follow with no end in sight. Furthermore, the
      diagnosis of a so-called intoxication of psychical disordered patients,
      especially those with a masked depression, can prevent a necessary medical or
      psychotherapeutic treatment. Disorders will be felt more and more as somatic and
      get a chronical course so that they are finally resistant to therapy.

PMID- 8571502
TI  - [Comment on N. Worm: Nutrition and coronary heart disease: how important is
      diet?].

PMID- 8571503
TI  - [Comment on E. Fritze, K.M. Muller: Cardiac death and acute myocardial infarct
      after psychological and physical stress].

PMID- 8571504
TI  - [Comment on W. Brand: Ambulatory rehabilitation--effectiveness and cost savings].

PMID- 8571505
TI  - Developing the relationship between animals and man.

PMID- 8571506
TI  - Necrotising enteritis in suckled calves.
AB  - Necrotising enteritis is a newly recognised disease affecting two to three-month
      old suckled calves in Scotland. A cohort of 10 calves from an affected herd was
      closely monitored from birth until the risk period was over, and one case
      occurred. In addition, all the cases of dysentery in suckled calves reported to
      SAV Veterinary Services, St Boswells, from April to August of 1992 were
      investigated and a further five outbreaks of necrotising enteritis were
      identified. The clinical pathology, gross and histological findings and results
      of microbiological investigations are described. No aetiological agent was
      identified and although the condition bore a superficial resemblance to mucosal
      disease the histological changes were distinct from those of mucosal disease and
      no bovine viral diarrhoea virus antigen was detected.

PMID- 8571507
TI  - A putative role for larval nematode infection in diarrhoeas of lambs which did
      not respond to anthelmintic drenches.
AB  - Attempts to control a summer diarrhoea in grazing Finnish landrace lambs which
      had been unresponsive to anthelmintics and coccidiostats were made by
      supplementing them with cupric oxide particles and withdrawing a magnesium-rich
      mineral, while maintaining parasite control measures. The diarrhoea persisted
      from July to September and plasma pepsinogen activities were raised, suggesting
      that the anthelmintic did not prevent abomasal damage; the jejunum of an affected
      lamb showed lesions of parasitic gastroenteritis. Small responses to cupric oxide
      particles and larger responses to the withdrawal of magnesium were deceptive,
      possibly being confounded by differences in parasite challenge. In another
      experiment Finnish landrace lambs were more susceptible to diarrhoea than Suffolk
      cross lambs in autumn. The susceptibility was then linked to a strong inhibition
      of worm egg output and may have been caused by a hypersensitive mucosal response
      to the larval challenge. Plasma pepsinogen concentrations were again raised in
      the Finnish landrace lambs and did not decline after treatment with anthelmintic,
      whereas the concentrations increased later in the Suffolk cross lambs, and were
      apparently responsive to anthelmintic. The cases of diarrhoea were similar to
      'July disease' and may have been caused by continuous nematode infections which
      were only briefly controlled by drenches. Anthelmintic-unresponsive diarrhoea is
      the term proposed for the disorder, which may be controllable by devices
      releasing anthelmintic continuously or by a move to less infected pasture. Faecal
      egg counts remained low in the condition and were diagnostically misleading.

PMID- 8571508
TI  - Dermocystidium koi found in skin lesions in koi carp (Cyprinus carpio).

PMID- 8571509
TI  - Docking of puppies' tails.

PMID- 8571510
TI  - Veterinary manpower.

PMID- 8571511
TI  - Veterinary manpower.

PMID- 8571512
TI  - Botulism in water birds.

PMID- 8571513
TI  - Leg problems in turkeys associated with Chlamydia psittaci.

PMID- 8571514
TI  - Welfare of caged birds.

PMID- 8571515
TI  - [X-ray semiotics of sialolithiasis in functional digital subtraction
      sialography].
AB  - Twenty-seven patients with sialolithiasis were examined using functional
      subtraction sialography developed by the authors. Differential diagnostic signs
      characterizing the degree of involvement of the salivary gland were defined. High
      efficacy of the method helps correctly plan the treatment strategy.

PMID- 8571516
TI  - [Potentialities of CT with densitometry in the assessment of local diffusion of
      esophageal cancer].
AB  - Computer-aided tomographic (CT) examination of 94 patients with esophageal cancer
      was carried out. Densitometric analysis of computer image of esophageal tumors
      making use of profile density histograms is presented for the first time.
      Objective graphic criteria for assessment of the depth of tumor invasion have
      been developed. CT results were correlated to intraoperative findings and data of
      histological examination of removed tumors. The sensitivity of the method in
      assessment of esophageal cancer dissemination was 97.7%, specificity 93.4%.

PMID- 8571517
TI  - [Errors and difficulties in emergency x-ray diagnosis of traumatic ruptures of
      the diaphragm].
AB  - A clinical and x-ray analysis of 30 cases with closed ruptures of the diaphragm
      and concomitant injuries is presented. Some aspects in the methodology of x-ray
      examination of patients with grave combined injuries are discussed and the
      importance of early contrast examination of the gastrointestinal tract
      emphasized. The author analyzes the difficulties associated with and errors
      occurring in x-ray examination. Some errors may be due to inappropriate timing of
      x-ray contrast examination. Rupture of the diaphragm may have no clear-cut x-ray
      signs in the first hours of the injury because of hemothorax, but a dynamic x-ray
      monitoring helps timely diagnose it.

PMID- 8571518
TI  - [Gastric cancer: diagnostic problems].
AB  - Gastric cancer is still one of the most prevalent cancer diseases. Despite a more
      than 30-year priority use of endoscopy in the diagnosis of gastric cancer, this
      condition is still virtually impossible to be detected at early stages. Many-year
      experience gained by the authors permitted them formulate two causes of this
      rather poor state of the art: 1) no screening programs for the early detection of
      gastric cancer and 2) under-valuation of the frequency of endophytic
      (infiltrative) forms of gastric tumors and of potentialities of modern x-ray
      examination in the diagnosis thereof. According to their results, gastric cancer
      was diagnosed in 539 cases out of more than 40,000 screenings. Analysis of more
      than 2,000 common clinical cases of gastric cancer brought the authors to a
      conclusion that endophytic, infiltrative (intraparietal) form of malignant tumor
      growth is the major form. A new sign of initial manifestations of intraparietal
      gastric cancer is suggested: intraparietal blastomatous infiltration symptom. The
      authors emphasize that roentgenology should again become the principal method in
      the diagnosis of gastric cancer. Only combined use of roentgenology and endoscopy
      may appreciably improve the detection rate of this grave disease.

PMID- 8571519
TI  - [Use of an x-ray method in the assessment of changes in the intestinal wall in
      colonic diverticulosis].
AB  - The authors analyze x-ray findings in 194 patients with colonic diverticulosis
      and its inflammatory complications. Findings of preoperative irrigoscopy were
      correlated with dates of morphological investigations. Roentgenomorphological and
      functional changes were assessed in different clinical types of colonic
      diverticulosis. Correlation was received between this changes and clinical sings
      of disease. Authors determined risk-groups of inflammatory complications of
      colonic diverticulosis.

PMID- 8571520
TI  - [Balloon dilatation of Stenon's duct in the treatment of sialolithiasis].

PMID- 8571521
TI  - [Multiple acquired esophageal cysts].

PMID- 8571522
TI  - [Gastric lipoma (a 30-year follow-up)].

PMID- 8571523
TI  - [Bezoar after stomach surgery complicated by small intestine ileus].

PMID- 8571524
TI  - [X-ray diagnosis of pancreatic diseases].
AB  - Modern means and methods including ultrasonic scanning, computer-aided tomography
      and magnetic imaging, retrograde endoscopic cholangiopancreaticography give
      objective information about the type of changes in the pancreas in the majority
      of cases and help recognize diseases of this organ at comparatively early stages
      of their development, permit assessment of the extent of involvement, detection
      of complications, monitoring of the disease course, and prediction of its course
      and outcome. Today ultrasonic examination and x-ray computer-aided tomography are
      methods of choice in the diagnosis of pancreatitis. These methods help assess the
      depth and extent of the involvement, assess the type of changes, detect
      complications, monitor the disease course and treatment efficacy, carry out
      purposeful drainage, and predict the disease course. The potentialities of these
      two methods in the diagnosis of pancreatic tumors are virtually equal. When
      ultrasonic scanning is ineffective, computer-aided tomography should be resorted
      to. In mechanical jaundice, if both the above methods fail to reveal the caise of
      gall duct obstruction, endoscopic retrograde cholangiopancreaticography or
      transcutaneous transhepatic puncture of the biliferous duct is recommended.

PMID- 8571525
TI  - [Regression of portal vein thrombus after intravascular treatment of a patient
      with hepatic metastasis of carcinoid].

PMID- 8571526
TI  - [Spinal echinococcosis].

PMID- 8571527
TI  - [Important landmark in the history of Russian military radiology (the 80th
      anniversary of the beginning of World War I)].

PMID- 8571528
TI  - [Results of multimodal treatment of patients with glial tumors of cerebral
      hemispheres].
AB  - The outcomes of multimodality treatment were assessed in 42 patients with glial
      tumors of cerebral hemispheres. Radical surgery turned out to be feasible only in
      52.4% of patients with high-grade tumor histological variants and 66.7% of
      patients with low-grade tumors. Five-year survival rates did not improve when a
      cumulative radiation dose was increased from 33 to 70 Gy and amount to 21.4 and
      73.8% in high- and low-grade tumours, respectively.

PMID- 8571529
TI  - [Radiodiagnosis of volumetric pathological formations of the brain stem].
AB  - Fifteen patients with volumetric abnormal formations of the brain stew were
      studied. All the patients underwent craniography and computed tomography (CT);
      magnetic resonance tomography (MRT) and cerebral angiography were conducted in 6
      and 8 patients, respectively. The studies provided a full-value differential
      diagnosis and revealed the following abnormal changes: brain stem tumors in 8
      patients, intratruncal hematomas in 6, and arteriovenous malformations in. 1. MRT
      was ascertained to be the most informative technique in the diagnoses of
      volumetric abnormal formations. The advantage of MRT over CT is not only to
      obtain three-dimensional tomograms, but to use various pulse sequences, allowing
      for a valid differential diagnosis of tumors and intratruncal hematomas. MR
      angiography is a promising trend in the diagnosis of tumors and vascular
      malformations.

PMID- 8571530
TI  - [Magnetic resonance tomography in comprehensive examination in epilepsy in
      children].
AB  - The paper presents the results of examining 100 children suffering from various
      epilepsies by magnetic resonance tomography, which determined a morphological
      substrate of the disease in 26%. The findings were compared with the clinical
      picture and the results of routine study tools (skull X-ray, EEG, EchoEG, REG).
      The diagnostic value of the techniques applied was defined. It is concluded that
      a set of diagnostic tools rather than individual techniques should be applied to
      reveal etiological and pathogenetic factors of the disease.

PMID- 8571531
TI  - [Possibilities of ultrasonography in the diagnosis of sex differentiation
      disorders in children].
AB  - Ninety-five children with different forms of hermaphroditism aged 3 months to 14
      years were examined to assess the potentialities of echography. Ultrasonic
      examinations of the kidneys, adrenals, pelvic organs (with full bladder, during
      and after miction), scrotum, and inguinal area were carried out. Echographic
      picture of urogenital organs in mixed ovarian dysgenesis, congenital deficiency
      of testosterone biosynthesis or metabolism due to enzymatic deficit, testicular
      feminization, congenital adrenocortical dysfunction was analyzed and criteria of
      differential diagnosis of these conditions discussed. The informative value of
      the method was assessed. Ultrasonic findings were compared with the data other
      diagnostic methods and reliability and high sensitivity of ultrasonography was
      demonstrated.

PMID- 8571532
TI  - [Diagnosis of kidney diseases in children].

PMID- 8571533
TI  - [Ultrasonic diagnosis of cavernous transformation of the portal vein in newborn
      infants].

PMID- 8571534
TI  - [X-ray diagnosis of Pfeiffer's syndrome (type V of acrocephalosyndactyly)].

PMID- 8571535
TI  - [A case of a DIL cava filter migration into the suprarenal portion of the
      inferior vena cava].

PMID- 8571536
TI  - [Precautionary measures in magnetic resonance studies].

PMID- 8571537
TI  - [Essay on establishment and development of pediatric radiology].

PMID- 8571538
TI  - [Use of Omniscan (gadodiamide) in magnetic resonance studies of the central
      nervous system (results of a multicenter study)].
AB  - The aim the study: was to conduct first in Russia multicenter trial of
      gadodiamide in brain and spine MRI in adult patients. Open noncomparative
      multicenter (5 clinical centres) study. Brain and spine MRI was performed in 190
      adult patients with signs of CNS disorders. Field strength of MR imagers was 0.04
      1.5 T. Gadodiamide ("Omniscan", "Nycomed Imaging", Nycomed) was injected IV in
      dose 0.1 mmol/ml. Contrast enhancement was obtained in 74% cases. Gadodiamide
      allowed to detect more new lesions, better differentiate borders and internal
      structure of lesions, to differentiate them from oedema and surrounding
      structures. Contrast-enhanced MR images were superior to non-enhanced T1 and T2
      weighted images and to CT images (before and after contrast enhancement). Use of
      gadodiamide increased confidence in diagnoses in 90.4% cases, changed the
      diagnosis in 30.3% cases. The general number of adverse events was 2.6%. Adverse
      reactions to gadodiamide were seen in 1.6%; all of them were of mild intensity
      without need for therapy. Gadodiamide is an effective and safe nonionic
      paramagnetic contrast media for brain and spine MRI in adult patients.

PMID- 8571539
TI  - [Materials for the Federal program of the development of x-ray diagnosis].

PMID- 8571540
TI  - Porcine TNF: a review.
AB  - One of the classical animal model systems in the study of important
      cardiovascular diseases, such as septic shock is that of swine. Important
      mediators of such disease states are different cytokines, among them tumor
      necrosis factor alpha (TNF-alpha) and beta (TNF-beta). This review aims to
      summarize the current knowledge about the primary structure and the regulation of
      the porcine TNF genes, as well as methods used to measure their respective
      proteins.

PMID- 8571541
TI  - A single nucleotide insertion in the canine interleukin-2 receptor gamma chain
      results in X-linked severe combined immunodeficiency disease.
AB  - The immunologic and genetic analysis of a 14-week-old-male cardigan Welsh corgi
      puppy that presented with failure to thrive, diarrhea, and intermittent vomiting
      are described. The lack of palpable lymph nodes, the premature death of a male
      sibling, and similar clinical signs in a male cousin suggested that a primary
      immunodeficiency disease might be responsible for his poor clinical condition.
      Quantitation of serum immunoglobulins revealed low concentrations of IgG and
      undetectable IgA, yet normal concentrations of IgM. A complete blood cell count
      showed a slight anemia and lymphopenia. Although the peripheral blood contained a
      normal percentage of T cells, with an increased CD4:CD8 ratio, they were unable
      to proliferate in response to phytohemagglutinin (PHA) and/or interleukin 2 (IL
      2). Furthermore, following PHA activation, the peripheral blood lymphocytes (PBL)
      demonstrated a nearly complete lack of IL-2 binding. All of these laboratory
      findings were identical with our previous findings from dogs with X-linked severe
      combined immunodeficiency (XSCID) that is due to a mutation in their IL-2
      receptor gamma (IL-2R gamma) chain. Examination of the corgi's IL-2R gamma cDNA
      revealed an insertion of a cytosine following nucleotide 582, resulting in a
      premature stop codon prior to the transmembrane domain. The insertion also
      created an EcoO109 restriction enzyme site that enabled us to detect the mutation
      in the patient's genomic DNA. This new mutation in the IL-2R gamma chain
      discovered in a cardigan Welsh corgi puppy results in XSCID with similar
      immunologic abnormalities as observed in dogs with the same disease resulting
      from a different IL-2R gamma chain mutation.

PMID- 8571542
TI  - Identification of a dog IgD-like molecule by a monoclonal antibody.
AB  - IgD has not been identified in dogs. We produced a monoclonal antibody (mAb)
      designated 9B during the production of hybridomas to dog IgE. Using Western blot
      analysis under non-reducing conditions, the mAb (9B) recognized a predominant
      protein band of 185 kDa which was also recognized by anti-dog IgG F(ab')2,
      suggesting that this 185 kDa protein is an immunoglobulin (Ig) containing light
      chains. Under reducing conditions, the mAb (9B) recognized only one protein band
      of 55 kDa which presented a distinct molecular weight (MW) and immunoreactivity
      from the dog tau, mu, alpha, and epsilon chains. The 55 kDa band did not react
      with anti-dog IgE, IgM, IgA, and IgG, but did react with the mAb (9B). The MW was
      75 kDa for the epsilon chain, 77.5 kDa for the mu chain, 58 kDa for the alpha
      chain, and 52 kDa for the tau chain. Further, by immunofluorescent staining, this
      Ig recognized by the mAb (9B) was found on the surface of dog lymphocytes.
      Studies of this dog Ig with the mAb revealed that this Ig bound to protein A and
      protein G-Sepharose, and that its enzyme-linked immunosorbent assay (ELISA)
      activity as measured by the mAb (9B) did not change after heating at 56 degrees C
      for 2 h. Ragweed-specific IgG, IgE, and this newly defined Ig significantly
      increased when dogs were immunized with ragweed extract. These data suggest that
      this Ig is a previously unrecognized IgD-like molecule in dogs.

PMID- 8571543
TI  - Red blood cell glycophorins as B and T-cell antigens in canine autoimmune
      haemolytic anaemia.
AB  - Pathogenic autoantibodies from two dogs with autoimmune haemolytic anaemia (AIHA)
      were shown to react with glycophorin from the canine red blood cell (RBC)
      membrane. Autoantibodies in both cases bound to purified glycophorin in enzyme
      linked immunosorbent assays (ELISAs), and the major autoantigen
      immunoprecipitated by the antibodies corresponded in apparent molecular mass with
      glycophorin. Furthermore, neuraminidase treatment of the precipitated antigen, or
      of canine glycophorin, resulted in identical changes in apparent molecular mass
      in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Such
      removal of sialic acid from glycophorins was demonstrated to cause shifts in SDS
      PAGE migration that are unique among RBC membrane proteins. In two further cases
      of AIHA, where autoantibodies did not immunoprecipitate the glycophorin pattern,
      ELISAs revealed that RBC-reactive IgG was present in serum and RBC elutes, but
      that these antibodies failed to bind to canine glycophorin. Thus, we consider
      that autoantibodies specific for glycophorin are present in some, but not all,
      dogs with AIHA. T-cells from a case of AIHA proliferated in vitro in response to
      autologous RBC, or to multiple RBC membrane components fractionated by SDS-PAGE.
      Three fractions, corresponding to major glycophorins, to the RBC anion channel
      band 3, and to spectrin from the membrane skeleton, were stimulatory. In
      contrast, T-cells from healthy dogs failed to respond to RBC, or to any blot
      fractions with the exception, in one animal, of the fraction bearing spectrin. It
      is suggested that activation of autoreactive T-cells with multiple specificities
      may be necessary to provide sufficient help for pathogenic autoantibody
      production.

PMID- 8571544
TI  - Monoclonal antibodies specific for equine IgG sub-isotypes including an antibody
      which recognizes B lymphocytes.
AB  - Equine immunoglobulin G is currently classified as consisting of five sub
      isotypes: IgGa, b, and c, IgG(T), and IgG(B). The study of the role of these
      immunoglobulins in antigen-specific responses, and the examination of their
      functional properties would be greatly facilitated by the availability of
      monoclonal antibodies (Mabs) that distinguish between them. The production and
      characterization of two Mabs that recognize an IgG sub-isotype with the
      characteristics of IgG(ab) is described. The immunoglobulin identified by these
      Mabs had a heavy chain weight of 53 kDa, was of rapid cathodal electrophoretic
      mobility in immuno-electrophoretic analysis, and reacted only with anti-sera to
      IgG, and not with anti-sera to IgG(T), IgA, or IgM in radial-immunodiffusion
      analysis. In addition, one of these two Mabs (CVS1) also recognized the majority
      of peripheral blood B lymphocytes in indirect immunofluorescent staining
      analysis, suggesting either that equine IgD may share a common antigenic epitope
      with an IgG sub-isotype, or that a large proportion of equine B lymphocytes may
      express an IgG sub-isotype on their surface.

PMID- 8571545
TI  - The behaviour of monoclonal antibodies in the First International Pig CD Workshop
      reacting with gamma delta/Null T lymphocytes in the blood of SLAb/b line pigs.
AB  - Further studies were carried out on the monoclonal antibodies (mAbs) from the
      First International Swine CD Workshop which react with gamma delta Null T
      lymphocytes, defined by the binding of mAb w020/141 (MAC320) as Swine Workshop
      Cluster number SWC6. Studies were also carried out on several other mAbs from the
      same workshop which identify other CD antigens, but whose binding is not
      restricted exclusively to gamma delta Null T-lymphocytes. The first group
      consists of 11 mAbs (w021, w022, w059-w065, w105 and w117) and the second group
      of 18 mAbs (w008, w026, w056, w067-w071, w080, w091-w094, w110, w111, w118, w119
      and w121). All mAbs were characterised by binding to peripheral blood lymphocytes
      (PBL) from normal, sham-thymectomized (STx) and thymectomized (Tx) pigs of the
      Babraham SLAb/b line and by their overlap, using two-colour immunofluorescence
      with biotinylated mAb MAC320 (w020/141), which identifies all gamma delta Null
      cell T-lymphocytes and the Null cell subpopulation identified by MAC319 (w021).
      The Null cell-specific mAbs were also used in inhibition studies of MAC319 and
      MAC320 binding and by staining PBL with pairs of mAbs together with either MAC319
      or MAC320. Based on these data we suggest a putative relationship of the Null
      cell subsets defined by these mAbs with each other.

PMID- 8571546
TI  - The surface phenotype of swine blood and tissue eosinophil granulocytes.
AB  - Cell surface antigens of swine eosinophil granulocytes were studied with flow
      cytometry and immunohistochemistry. The monoclonal antibody 335-2, specific for
      swine differentiation antigen swC1a, originally described to be present on swine
      T and myeloid cells, is able to distinguish swine eosinophils (swC1a negative)
      from neutrophils (swC1a positive). This monoclonal antibody (mAb) was used in two
      colour fluorescence measurements in combination with anti-swine -CD2, -CD4, -CD8,
      -MHC class II, -LFA-1 or -swC3 mAbs. All of the blood eosinophils proved to be
      positive for LFA-1 and swC3, a common marker of swine monocytes, granulocytes and
      macrophages. However, they do not react with antibodies recognizing swine CD2,
      CD4, CD8 or MHC class II cell surface molecules. The reactivity pattern of tissue
      eosinophils with these mAbs was determined on cryostat sections of different
      tissues of swine. Tissue eosinophils were negative for swC1a, CD2, CD8, while all
      of them reacted with swC3. In contrast with blood eosinophils, 10-30% of tissue
      eosinophils were demonstrated to be negative for LFA-1. In some cases, a few
      tissue eosinophils were found to be stained weakly by antibodies to swine CD4 or
      MHC class II antigens.

PMID- 8571547
TI  - Use of peroxidase:anti-peroxidase immune complexes as markers for Fc gamma
      receptors in vitro.
AB  - In species for which monoclonal antibodies are not yet available, the
      demonstration of Fc receptors has relied on a variety of ligand-based assays
      including the binding of antibody-coated erythrocytes, radiolabeled monomeric
      immunoglobulin, and non-physiologic aggregates of immunoglobulin. In order to
      study the binding of small immune complexes to Fc receptors on canine monocytes,
      a new method was developed using an enzyme-linked immune complex. The ability of
      rabbit polyclonal peroxidase:anti-peroxidase (PAP) immune complexes to bind to
      freshly isolated canine peripheral blood monocytes was characterized using
      standard ELISA techniques. The binding of rabbit polyclonal PAP to monocytes was
      time and concentration dependent and reversible. This binding was saturable with
      increasing concentrations of PAP and could be blocked by soluble rabbit IgG or
      rabbit Fc fragments. The blocking and saturation curves for canine monocytes were
      suggestive of multiple classes of Fc gamma binding sites. In contrast to intact
      PAP complexes, the binding of F(ab) PAP preparations or free horseradish
      peroxidase was minimal. The use of commercially available PAP preparations
      provides a reproducible, inexpensive, and non-radioactive measure of Fc gamma
      receptor binding on canine cells. In addition, these findings suggest caution in
      using heterologous PAP as a histochemical reagent in tissues expressing Fc gamma
      receptors.

PMID- 8571548
TI  - Comparison of ovine lentivirus detection by conventional and recombinant
      serological methods.
AB  - Recombinant (r) transmembrane protein (TM), major capsid protein P25, and matrix
      protein P16 of ovine lentivirus (OLV) were used as solid phase antigens in enzyme
      linked immunosorbent assays (ELISAs) for the detection of specific antibodies
      against OLV in sheep sera. Sensitivity, specificity, and agreement of these three
      recombinant assays were compared with each other and with two currently available
      conventional OLV serological assays, the agar gel immunodiffusion (AGID) test and
      a whole-virus (WV) ELISA. Field sera from a total of 412 Midwestern United States
      sheep were tested and compared by the five OLV detection methods, including
      visibly healthy sheep selected for public sale (Group A, n = 171), samples from a
      breeding flock of Finnsheep and Finn-cross ewes (Group B, n = 184) and moribund
      sheep with clinical signs associated with OLV (Group C, n = 57). The rTM ELISA
      was the most sensitive OLV detection assay, both overall and within each group.
      Sera from 48.1% (198/412) of field samples were rTM ELISA positive. By contrast,
      positive rates for the rP25, rP16, and WV ELISAs and AGID test were 34.2%, 32.3%,
      36.9%, and 26.9%, respectively. The rTM ELISA reactivity was 36.8% for Group A
      sera, 50.0% for Group B sera, and 75.4% for Group C sera. Among the 21 Group C
      sheep possessing OLV lung lesions at necropsy, 20 (95.2%) were rTM ELISA
      positive. The greatest test agreement occurred between the rP25 and the rP16
      ELISAs. The data suggest that the recombinant TM immunoassay is the most accurate
      and sensitive of the five methods evaluated for the detection of serum anti-OLV
      antibodies in sheep, both at the subclinical infection and overt clinical disease
      stages.

PMID- 8571549
TI  - Antigen specificity of the ovine cytotoxic T lymphocyte response to bluetongue
      virus.
AB  - Bluetongue virus (BTV), an arbovirus transmitted by midges, can cause serious
      disease in sheep. Both virus neutralizing antibody and cytotoxic T lymphocytes
      (CTL) have been shown to have a role in protective immunity. In this study, the
      antigen specificity of CTL from BTV-immune sheep has been determined using
      recombinant vaccinia viruses expressing individual BTV antigens. The results show
      that, in the sheep studied thus far, the serotype-specific outer coat protein,
      VP2, and the non-structural protein, NS1 are major immunogens for CTL, with VP5
      (an outer coat protein) and NS3 being minor immunogens. No VP7 (a major group
      reactive inner coat protein) specific CTL were detected. The CTL from sheep
      immunized with serotype 1 were cross-reactive and able to recognize target cells
      infected with other BTV serotypes. Further work demonstrated that the cross
      reactive CTL recognized NS1, but not VP2.

PMID- 8571550
TI  - Development and application of an antibody ELISA for the marker protein of ovine
      pulmonary carcinoma.
AB  - Ovine pulmonary carcinoma (OPC) is a contagious pulmonary neoplasia with a
      suspected retroviral etiology. The major core protein (P27) of the putative OPC
      virus cross-reacts with antibodies to P27 of the Mason-Pfizer monkey virus
      (MPMV), a type-D retrovirus. This serological reactivity serves as the only
      accepted biological marker for OPC. In order to make a useful reagent for the
      detection of the OPC marker for serodiagnosis and epidemiological studies, the
      MPMV-P27 coding region was cloned and expressed in Escherichia coli. Gel purified
      recombinant MPMV-P27 protein was used to develop an immunoassay. This recombinant
      enzyme-linked immunosorbent assay (ELISA) was then used to screen 223 sera from
      US sheep and 176 sera from Italian sheep. In this study, we found: (1) a high
      prevalence of infection with the putative OPC retrovirus in sheep with chronic
      pneumonia; (2) a subclinical infection with OPC virus may be more common in US
      sheep than indicated by the rare recorded occurrence of pulmonary carcinoma; (3)
      an apparent association between ovine lentivirus (OLV) and OPC infection.

PMID- 8571551
TI  - Homotypic aggregation of ovine leucocyte induced by anti-leucosialin (CD43)
      monoclonal antibodies.
AB  - Four monoclonal antibodies directed against ovine/bovine leucocyte antigens
      (Co.44B8, Co.11F10, Co.33B3 and Co.26F4) were produced and all recognized an
      antigen with an apparent molecular weight of 105 kDa under reducing conditions.
      This molecule was considered to be the ovine/bovine analogue of human, rat and
      mouse CD43 or leucosialin. This conclusion was based on (a) the cellular
      distribution of the antigen which was similar to that described in other species,
      (b) a decrease of apparent M(r) (150 kDa) after treatment with neuraminidase, and
      (c) production of cell aggregation by the four monoclonal antibodies and the
      influence of temperature and metabolic inhibitors on this phenomenon. Co.44B8,
      Co.11F10, Co.33B3 and Co.26F4 all recognized and immunoprecipitated the molecule
      after neuraminidase treatment of the cells. The data indicate an important
      function of CD43 as a mediator of cell aggregation for ruminant cells.

PMID- 8571552
TI  - Immunohistochemical localization and biological significance of the
      phylogenically conserved thymus-brain antigen (UB-13 antigen) in skate, rat and
      human.
AB  - A monoclonal antibody (UB-13) originally raised against the brain of the skate
      (Raja kenojei, a cartilaginous-fish) was found to react with lymphoid and brain
      tissues from many species when examined immunohistochemically. In rat and human
      thymus, UB-13 antigen was observed to be closely associated with reticular tissue
      in the medulla and cortex. Interestingly, a few or several thymocytes were
      encircled by the UB-13-reactive reticular tissue. At 14 days gestation, rat
      thymus consisted mainly of reticular epithelial tissue, after which strong
      thymocyte production started. At this stage, some of the reticular tissue was
      heavily stained with UB-13. In the thymus tissues of the irradiated and
      recovering rats, where reduction and massive reproduction of thymocytes were
      observed, extensive UB-13 antigen expression localized on the reticular
      epithelial tissue, an observation which may support the thymocyte re-population.
      These findings suggest that the antigen recognized by UB-13 may be important for
      thymocyte proliferation and maturation. UB-13 antigen was found in the fibrous
      structure of the molecular and granular layer of the human cerebellum. Some glial
      cells were also stained strongly with UB-13 in the human cerebellar or cerebral
      grey and white matter. In rat, glial cells, especially astroglias, and the
      endothelial structure of blood vessels were stained strongly with UB-13. These
      findings suggest that UB-13 may be a useful monoclonal antibody for analysis of
      brain-lymphoid antigen in many species.

PMID- 8571553
TI  - Immune functions in beluga whales (Delphinapterus leucas): evaluation of
      phagocytosis and respiratory burst with peripheral blood leukocytes using flow
      cytometry.
AB  - Flow cytometric assays using peripheral blood were developed to study
      phagocytosis and respiratory burst, the two major functions of neutrophils and
      among the most important non-specific defense mechanisms, in beluga whales. The
      use of flow cytometry avoids the problems associated with the isolation and
      purification of different cell types, and allows the measurement of a large
      number of cells (10,000) in a very short period of time. The methods described
      will be used to compare these functions in blood samples from highly contaminated
      beluga whales from the St. Lawrence and from relatively clean arctic beluga
      whales.

PMID- 8571555
TI  - [The organization and modern principles of the treatment of periodontitis in the
      Armed Forces].
AB  - The article deals with the questions of spreading and the structure of
      periodontitis among servicemen, as well as the peculiarities of prophylaxis and
      medical care in military units and medical institution. The authors show the
      priority of surgical methods of treatment (curettage, flap operation).
      Characteristic features of pre-operational preparation are described, as well as
      methods of conservative treatment (general and local), and professional hygiene
      of the oral cavity.

PMID- 8571554
TI  - Partial sequence of the equine immunoglobulin epsilon heavy chain cDNA.
AB  - In order to isolate a part of the immunoglobulin E (IgE) heavy chain cDNA of the
      horse, primers have been designed based upon well conserved sequences in humans,
      sheep and rats. The PCR resulted in a 500 bp fragment which hybridised with a
      human IgE constant region probe. The fragment was cloned and sequenced and its
      derived protein sequence compared with the corresponding sequences in humans,
      sheep and mice. Most amino acids common to these three species are also shared by
      the horse.

PMID- 8571556
TI  - [The diagnosis of poisonings by technical fluids].
AB  - More than 300 cases of severe poisonings with toxic technical liquids were
      analysed (methanol, dichlorethane, "medium" spirits, ethylenglycole and its ethyl
      ether, tetrahydrofurfuric alcohol). Various signs of intoxications are shown,
      clinical symptoms, as well as its dynamics, diagnostic significance, some
      diagnostic errors and methods of its prevention. A conclusion is made concerning
      the necessity of a complex approach towards differential diagnosis of acute
      poisonings with toxic technical liquids.

PMID- 8571557
TI  - [The toxicological assessment of hazardous explosive compounds].

PMID- 8571558
TI  - [The histocompatibility problem in military blood transfusions].
AB  - One of the basic approaches which provides for the increase of immunological
      safety of hemocomponental therapy is the use of donor-recipient histocompatible
      blood. The decisive factor in the organism's individuality is HLA-antigen system.
      Antigen incompatibility of donor's and recipient's tissues in HLA-antigen causes
      the development of delayed hypersensitivity and sensibilization of the recipient,
      which provoke a number of complications and posttransfusion reactions.
      Histocompatibility is the key problem for modern transfusiology and
      transplantology.

PMID- 8571559
TI  - [Experience with the use of pulsed plasmapheresis in therapeutic practice].

PMID- 8571561
TI  - [Biliary secretory function after Roux gastric resection].

PMID- 8571560
TI  - [The efficacy of treating skin ulcers and burns with film dressings with
      antibiotics].
AB  - The article summarizes the results of studies conducted during the treatment of
      burns (108 patients), and ecthymas (85 patients) with the help of film dressing
      and antibiotic powder (R. Breitman's method). During application of this method
      the healing process was more rapid, the administration of antibiotics was
      minimum, the dressing process became more easy, good cosmetic results were
      obtained. The period of inpatient care was shortened, cost of treatment was
      reduced.

PMID- 8571562
TI  - [The outcomes of reconstructive-reparative operations in atherosclerotic lesions
      of the femoral-popliteal segment].

PMID- 8571563
TI  - [Licensing and the work routine of military medical institutions under medical
      insurance conditions].
AB  - The article describes preparatory formalities for licence granting for military
      medical institutions, list of documents which must be produced for the Licence &
      Accreditation Commission on Medicine and Pharmacology. Rights and duties of
      licensees are described, peculiarities of license for military medical
      institutions, regulations of medical care for patients, account of funds and
      profits obtained in the result of implementation of programs on obligatory and
      volunteer medical insurance.

PMID- 8571564
TI  - [The dynamic cytochemical indices of the blood in helicopter pilots who
      participated in the cleanup of the aftermath of the accident at the Chernobyl
      Atomic Electric Power Station].

PMID- 8571565
TI  - [The sequelae of accident situations on board ships of the Black Sea fleet and
      the organization of medical care for the victims].

PMID- 8571566
TI  - [The results of government (military) trials of a pilot sample of a mobile
      clinico-diagnostic laboratory].

PMID- 8571567
TI  - [The ergonomic quality assessment of military medical engineering].

PMID- 8571568
TI  - [Mathematical modelling in planning the medical stores support for the troops].

PMID- 8571569
TI  - [The southern sector (from the notes of a military physician)].

PMID- 8571570
TI  - [Boris Aleksandrovich Samotokin (on the 80th anniversary of his birth)].

PMID- 8571571
TI  - [The medical technical problems of chemical protection for the Russian Army in
      the First World War].

PMID- 8571572
TI  - [The length of the service time of servicemen performing their service under
      contract].

PMID- 8571573
TI  - [The 30th anniversary of the Chair of Military Field Surgery in the Military
      Medicine Department of the Saratov State Medical University].

PMID- 8571574
TI  - [The polyclinic--the central stage in rehabilitative treatment].

PMID- 8571575
TI  - [Phosphoinositide response and changes in the supraoptic-neurohypophyseal system
      in individual resistance of rats to hypoxia].
AB  - The dynamics of phosphatidyl inositol, phosphatidyl inositol-4-phosphate and
      phosphatidyl inositol-4.5-diphosphate was studied in brain and liver tissues of
      rats with hypoxia developed as a result of treatment in the altitude chamber at
      6,000 m, daily 6 hrs, on day 30. The content of phosphatidyl inositol-4-phosphate
      and--4.5-diphosphate was increased on days 3 and 30 altitude post-training. This
      hypoxia caused impairments in brain circulation as well as led to increase in the
      hypophysis mass in lowly resistant rats within early periods of treatment and in
      highly resistant animals on day 30.

PMID- 8571576
TI  - [Changes in the proteolytic activity of venous blood leukocyte nuclei from gamma
      irradiated rabbits].
AB  - In terms of their capacity to decompose a casein substrate, the activity of
      nuclear proteinases was studied in the leukocytes of the rabbit blood taken
      before and after their joint gamma-irradiation. There was a substantial increase
      in the activity of proteinases in the leukocytic nuclei 2 and 48 hours after
      animals had been irradiated in a dose of 5 Gy as compared with those obtained
      prior to irradiation. Ninety six hours after irradiation the activity showed an
      average decrease to 40-60% of the control level. There was a correlation between
      the proteolytic activity and the irradiation dose: there were average 1.75- and
      3.25-fold activity increases with 2.5 and 5.0 Gy, respectively. The findings
      provide a rationale for examining the proteinase activity of human peripheral
      leukocytic nuclei to clinically estimate radiation exposures.

PMID- 8571577
TI  - [Changes in glycolysis and glycogenolysis in tissues and level of certain
      hormones in blood and urine from rats with varying lengths of cold adaptation].
AB  - The production phase changes of adaptive hormones and the activity of key
      glycolytic and glycogenolytic enzymes were studied in Wistar rats exposed to a
      long-term (1-49 day) cold (+5 degrees C) exposure. The allosteric mechanisms
      responsible for regulating carbohydrate metabolism were shown to interact with
      endocrine ones and to modulate their effects. In cold acclimation, activation of
      the sympathoadrenal system aimed not only at increasing carbohydrate metabolism,
      but at enhancing the metabolism of fats and calorigenic effects.

PMID- 8571578
TI  - [Biological monitoring of exposure to alkylating xenobiotics by determining them
      in complexes with plasma proteins, hemoglobin, mercapturic acids from urine of
      rats and industrial workers. I. Acrylonitrile].
AB  - A parent molecule of acrylonitrile (cyanoethylene, CE) may be isolated from its
      the model compound S-(2-cyanoethylene)-1-cysteine, as well as from its N-acetyl
      derivative and hemoglobin (Hb) and plasma proteins from the intoxicated animals
      and workers engaged in manufacturing synthetic rubber made from acrylonitrile.
      The developed procedure consists in the 1.5% H2O2 oxidation of a CE adduct for 30
      min, followed by addition of a sample into the gas chromatographic injector at
      250 degrees C, resulting in the release of CE from the adducts and in the current
      ingress of carrier gas into the capillary column in order to separate and
      determine with a FTD detector. There was a dose-response relationship between the
      formation of CE adducts with rat blood proteins, urinary mercapturic acids when
      the poison was given in a dose of 1-50 mg/kg. CE covalently bound to Hb was
      detected in the workers exposed to its monomer in working places.

PMID- 8571579
TI  - [Study of the spectrum of rabbit myocardium nuclear DNAases using models of
      ischemia and diabetes mellitus].
AB  - There were alterations in the spectrum of nuclear endo-DNAases in the rabbit
      myocardium on experimental models of diabetes mellitus and other diseases where
      the perfused heart was involved i.e. disappearance of the enzyme with 130 kDa
      from the control extracts was followed by a great increase in the content of low
      molecular forms in the nuclear preparations obtained from the ischemic heart, as
      well as that with 145 kDa in all the abnormalities under study.

PMID- 8571580
TI  - [Biological monitoring of exposure to alkylating xenobiotics by determining them
      using a new analytical approach in complexes with hemoglobin, plasma proteins and
      mercapturic acids in urine. II. Acrylamide].
AB  - A new simple and prompt procedure for measuring acrylamide (propenamide, PA) in
      PA-derived mercapturic acid, such as N-acetyl-S-(2-propenamide)-L-cysteine (N-Ac
      PAC), and in hemoglobin (Hb) and plasma protein adducts in the rats expose to PA
      was developed, by employing gas chromatography (GC). PA in mercapturic acids or
      proteins was liberated on high-temperature heating in an injector port during the
      working procedure of a GC capillary after preoxidation of sulfur atoms in PA
      bound cysteine to a sulfoxide form with hydrogen peroxide and analyzed. This
      method resulted in 87% of PA in authentic N-Ac-PAC. The number of PA released
      from the protein adducts was proportional to the cumulative dose of PA given at a
      concentration of 1-75 mg/kg during 1-3 weeks. The alkylating level of Hb was
      approximately 65 times higher than that of plasma proteins and it was nearly 6.5%
      of its cumulative dose. The index of binding to Hb and the rate of its alkylation
      were 163 and 0.75.10(-3) liter/g-1/hour-1, respectively.

PMID- 8571581
TI  - [Ability of bone marrow cells to generate active forms of oxygen in C57Bl/6 and
      BALB/C mice and mutagenic effects of dioxidine].
AB  - Phorbol-myristate acetate- and opsonized zymosan-induced statistically
      significant differences were shown in the intensity of chemiluminescence
      occurring in the bone marrow cell suspension. The bone marrow cells from male
      BALB/c mice showed the most pronounced response to stimulation in the two cases.
      After 5-day administration of dioxidine (300 mg/kg), the number of the injured
      metaphases in the bone marrow from the examined animals was 43.6 +/- 2.2 and 23.8
      +/- 1.9% in BALB/c and C57B1/6 mice, respectively, which provides evidence for
      marked strain-specific differences in the cytogenetic effect of this proxidative
      mutagen. The findings indicated that there was a relationship between the
      capacity of bone marrow cells of producing APA and the severity of cytogenetic
      lesions in these cells.

PMID- 8571582
TI  - [Radioprotective effect of a new pharmaceutical "glucosuccine"].
AB  - The experiments on 6-Gy irradiated rats have revealed that the new biologically
      active substance. Glucosuccine has a radioprotective effect which depends upon
      the route of administration. The agent was demonstrated to produce a profound
      radioprotective rather than therapeutical effects. Its administration for 30 days
      proved to be less effective than its triple use prior to and following
      irradiation.

PMID- 8571583
TI  - [Clastogenic activity of dietary sugar substitutes].
AB  - The present paper describes the possible clastogenic activity of the following
      synthetic sugar substitutes, such as cyclamate in daily doses of 11 and 110
      mg/kg, saccharin, 5 and 50 mg/kg, acesulfam, 15 and 150 mg/kg, sucralose, 15 and
      150 mg/kg, aspartame, 40 and 400 mg/kg, orally given to C57Bl/6 mice during 5
      days. No clastogenic activity was found in the compounds tested.

PMID- 8571584
TI  - [Vitamin E: immunocorrecting effect in bronchial asthma patients].
AB  - The examination of patients with bronchial asthma has established that vitamin E
      supplemented to their multimodality therapy produces an immunological effect. The
      decreased functional activity of T lymphocytes increases and their levels elevate
      in their peripheral blood. There was also an increase in the blood levels of B
      cells, by elevating the count of mature B lymphocytes and reducing that of
      immature B cells. Vitamin E enhances the phagocytic activity of peripheral
      granulocytes whereas the serum activity of lysozyme and complement declines.

PMID- 8571585
TI  - [Bioavailability and pharmacodynamics of various forms of synthetic beta-carotene
      in volunteers].
AB  - The biological availability of artificial beta-carotene as a water-soluble versus
      oily formulation based on cyclodextrin (Cyclocar tablets) was studied on
      volunteers given a single dose of 25 mg. The concentrations of beta-carotene and
      major carotenoids were measured in the blood serum during the experiment by high
      performance liquid chromatography. The maximum content of beta-carotene in the
      serum was attained 24-30 and 30-48 hrs after oily formulations and Cyclocar and
      were 48.0 +/- 7.7 and 28.1 +/- 3.6 mg/dl, respectively. The rate of beta-carotene
      utilization from Cyclocar was 2.2 times less than that from the oil paste.
      Besides, beta-carotene absorbed from these oily drugs retained in the blood serum
      for longer period than that form Cyclocar.

PMID- 8571586
TI  - [Features of B group vitamin metabolism and criteria for providing them to
      children suffering from celiac disease].
AB  - The investigation into the relationship between the concentration of vitamins B,
      the blood activity of vitamin B-dependent enzymes and the urinary excretion of
      their metabolites in 14 children of both sexes whose age was 4.5-10 years and who
      suffered from celiac disease has characterized their metabolic features. The
      criteria for vitamin B1 provision of these children differ from those in healthy
      children of the same age: the normal value of TDP effects is achieved with higher
      thiamine excretion which is more than 12 micrograms/h. Apparently, the plasma
      concentration of riboflavin greater than 14 ng/ml and its urinary excretion 6
      micrograms/h should be taken as a criterion for normal vitamin B2 provision.
      Though due to a small proportion of the examined children, criteria for vitamin
      B6 and nicotinic acid could not be defined. The excretion of 4-pyridoxylic acid
      in the whole concentration ranges of pyridoxylic coenzymes in the plasma of sick
      children was essentially lower than that in healthy persons.

PMID- 8571587
TI  - [Inhibition of formation of superoxide radicals in leukocytes of
      hypercholesteremic patients under the effect of a lipid platelet activation
      factor antagonist].
AB  - A platelet-activating factor (PAF) antagonist was found to inhibit superoxide
      production in the leukocytes of patients with type IIA hypercholesterolemia. PAF
      (10(-7)-10(-6) M) alone failed to stimulate superoxide production in intact or
      PAF-antagonist-treated leukocytes. The PAF-antagonist-induced inhibition of
      superoxide production was observed in the leukocytes from hypercholesterolemic
      patients whose plasma cholesterol levels varied from 8.3 to 14.0 mmole/l.

PMID- 8571588
TI  - [Change in glucocorticoid-binding function of transcortin in acute gastroduodenal
      hemorrhaging].
AB  - The glucocorticoid-binding function of transcortin was studied in the blood serum
      of 31 patients with gastroduodenal ulcer complicated by moderate hemorrhage. The
      patients received a routine multimodality therapy. Sixteen donors serves as a
      control. Labelled cortisol was used to determine the time course of specific
      glucocorticoid saturation of transcortin. The Scatchard analysis defined the
      number of specific transcortin binding sites, the association and dissociation
      constants of cortisol-transcortin complexes. The blood levels of cortisol and
      insulin were measured using test kits (France). In patients with hemorrhage
      complicated ulcer, the cortisol binding sites to transcortin substantially
      increased in number on days 7 to 14, and on the contrary, the association
      constant decreased. The serum content of endogenous cortisol significantly rose,
      starting from day 1 to day 14 of the onset of hemorrhage. Insulin levels
      significantly decreased only on days 14 of bleeding. In posthemorrhagic patients,
      the cortisol/insulin index drastically elevated and remained high within 14 days.
      A role of serum transcortin functional changes in patients with hemorrhage
      complicated ulcerous disease in metabolic and immunogenetic processes.

PMID- 8571589
TI  - [Expression of tenascin in lymphoid cells and changes in it upon exposure to low
      doses of x-rays].
AB  - The oncofetal protein tenascin was detected in some strains of lymphoid cells:
      murine myeloma X-63, murine hybridoma MLC-1 and K-48 and T-cell plasmacytoma MOLT
      4. This effect was in agreement with the concept that tenascin serves as a marker
      of cell malignancy; such a concept allows one to use the marker in the studies of
      X irradiation impact on hybridoma clones. A non-linear correlation was found
      between the content of tenascin and the irradiation dosage, by using two
      hybridoma strains. There might be alterations in the expression of tenascin in
      the cultured lymphoid cells while detecting the genotoxic effect produced by
      different damaging agents.

PMID- 8571590
TI  - [Selenium in blood serum and in tumors of patients with benign and malignant bone
      neoplasms].
AB  - The content of selenium in the serum and bones was compared in persons having no
      neoplasms and in patients with malignant and benign bone tumors. The mean level
      of selenium in the healthy femoral bone was 81 micrograms/kg, with more
      predominant accumulation in the epiphysis than in the metaphysis and diaphysis
      and with higher concentrations in the periosteum than in the cambial layer. The
      normal mean bone/serum selenium ratio was 0.74. This index varied 0.8 to 5.1 in
      patients with benign tumors and 2.3 to 10.0 in those with malignant tumors.
      Benign tumors were characterized by significant multiple variations of tumor
      selenium levels depending on the type of an abnormality with maximally observed
      values in giant-cell tumor. In patients with various osteosarcomas, the mean
      selenium content was decreased to 71% in the serum and increased up to 300% in
      the tumor. The examination of the impact of the type of non-adjuvant therapy on
      serum selenium levels in patients with bone tumors indicated a negative selenium
      effect in the application of radiation therapy and a positive selenium effect in
      the transfusion of bone marrow suspension and in the use of platidium or SAR
      regimen therapy.

PMID- 8571591
TI  - [Activity of blood antioxidant enzymes in chronic liver damage].
AB  - Patients with chronic hepatic disease have higher superoxide dismutase (SOD)
      activity and lower erythrocytic glutathione levels. There was a decrease in
      plasma SOD activity in cirrhosis, a feedback between the dismutase and oxidase
      activities of ceruloplasmin in cholestatic damages to the liver. Drug therapy
      resulted in positive dynamics in the levels of SOD, glutathione peroxidase,
      glutathione, ceruloplasmin, which is likely to be associated with the control of
      the enzymatic mechanisms of antioxidative protection. It is suggested that the
      enhanced erythrocytic SOD activity in hepatic diseases might trigger free radical
      oxidation.

PMID- 8571592
TI  - [Uric acid in blood serum and incidence of hyperuricemia in irradiated people.
      Connection with radioactive and nonradioactive factors].
AB  - A total of 1,002 workers aged 36 to 72 years who were engaged in atomic industry
      and exposed to external gamma-irradiation and incorporated plutonium 239 in a
      wide dosage range. The levels of uric acid (UA), the incidence of hyperuricemia
      and their association with 2 radiation and 12 nonradiation factors were studied
      in the examinees. There was a positive correlation between the purine metabolic
      parameters and the total dosage of external gamma-irradiation, sex (UC levels
      were higher in males than in females), body weight index, essential hypertension,
      and the type of haptoglobin 1-1. The influence of nonradiation factors on the
      parameters in question were substantially greater than that of external
      irradiation. Linear regression equations were derived for the dependence of the
      levels of UA and hyperuricemia upon the influencing factors.

PMID- 8571593
TI  - [Ways of improving chemical training of students at medical institutes].
AB  - The paper considers how to extend medical students' knowledge and to provide
      chemical education within the framework of routine curricula. For this, the paper
      proposes that the view of regarding general chemistry as chemistry of elements
      should be given up and that the first part of the routine course of general
      chemistry should be supplemented with aspects of general inorganic, organic, and
      physical chemistry, that course of biological organic chemistry should contain
      chemistry of cell elements, as generally accepted in the world, obviating its
      irrespective issues of general organic chemistry. The results of introducing the
      approaches in question into teaching practice at the author-headed Department of
      Medical Chemistry, Therapeutical Faculty, Tyumen Medical Institute are given.

PMID- 8571594
TI  - [The effect of emotional stress on carboxypeptidase H activity in sections of the
      rat brain with varying sensitivity to it].
AB  - The activity of carboxypeptidase H involved in metabolism of neuropeptides was
      studied in rats resistant and predisposed to emotional stress under normal and
      stress conditions. The enzymatic activity was higher in the striatum and
      hypothalamus of the rats predisposed to stress than that of stress-resistant
      animals. Emotional stress resulted in activation of the enzyme in these both
      groups of animals, while the dynamics of the enzyme activity depended on the
      resistance of animals to stress and the poststress interval. There was a
      correlation between the activity of carboxypeptidase H and the content of
      neuropeptides in animals with varying stress-resistance.

PMID- 8571595
TI  - [Neurorehabilitation: yesterday, today and tomorrow].
AB  - Rehabilitation has its roots in the so called "care for cripples", later on in
      the postcare of war victims. It is a new way that neurologists do a specialized
      task within rehabilitation. Increasing lifepan furthermore gives a great
      overweight to cerebrovascular patients for rehabilitations. Only a holistic
      aspect can coop with this new challenges. It has to regard the patient and his
      family as well as to create new ways in social politics. The "Vorarlberger
      Modelle" (organized by Barolin) has not only given postulates, but practically
      shown new ways for rehabilitation in the future.

PMID- 8571596
TI  - [Current status of primary and secondary prevention of cerebral apoplexy].
AB  - There exists quite a number of risk factors for primary and secondary prevention
      of stroke. Only in a synopsis with different etiologies and with different
      personal data one can define their dignity.

PMID- 8571597
TI  - [Management and treatment of elderly psychiatric patients by the general
      practitioner].
AB  - About one third of all elderly people suffer from psychosocial disturbances
      reducing their well-being, ability or independence. Those disturbances can be
      mitigated more often than expected by medical treatment, psychotherapy or other
      therapies. In this field it is above all the general practitioner who has to be
      engaged as gate keeper and case manager.

PMID- 8571598
TI  - [Systemic family therapy with stroke patients].
AB  - Systemic family therapy is an useful method of support in the rehabilitation of
      patients with strokes. The process of accepting the new conditions can be
      fostered within the network of relationships. This acceptance enables the patient
      and his family to develop a new meaningful future. The people involved have to
      consider new possibilities of organizing their relationships within their ideas
      and values according to their changed psychic needs.

PMID- 8571599
TI  - [Group respiratory biofeedback in complex neurorehabilitation].
AB  - Respiratory feedback is to be seen as an apparatus aided psychotherapy. Like
      other hypnoide psychotherapies it acts via the vegetative switch, enabling
      relaxation and dynamization, as well as intentional formula. Administration in a
      semi open group can be demonstrated within the frame work of neuro
      rehabilitations, mainly pain-rehabilitation. The action is to be seen as well
      somatotropic as psychotropic, within a holistic approach.

PMID- 8571600
TI  - [Outcome-oriented Barolin Neurorehabilitation Scale: 476 cases over 6 years-
      multi-nodal statistical correlation of neurorehabilitation groups in diagnosis,
      prognosis and outcome].
AB  - This evaluation documents practicability and scientific value of the scale, since
      many years developed in our institute and in use there. Patients with left
      hemispheric lesions suffer from stronger disturbances of eating than others.
      Systematic neurological rehabilitations leads to a marked increased unnecessity
      of catheterism and by that to a marked better social integration. Associate
      depression (after Barolin) is a main source of rehabilitation hospitalism (as
      called by Barolin). Multiple sclerosis and Morbus Parkinson give better outcomes
      than cerebro-vascular patients. A new finding that also proofs to be
      neurophysiologically interesting is that higher agedness is mostly a non-limiting
      factor for rehabilitation, as far as not lesser endavours produce a self
      fulfilling prophecy. However a slight limitation in higher age groups is to be
      found in the patients with lesions on the dominant hemisphere, whereas lesions on
      the subdominant hemisphere produce no limitation to rehabilitation at all by
      higher age.

PMID- 8571602
TI  - Differences and diversity: shall it be confrontation or creativity?

PMID- 8571601
TI  - [Neurorehabilitation/geriatric rehabilitation--goals achieved and aims from the
      viewpoint of the so-called "Vorarlberg Model"].
AB  - Together with building up a first neurological department in one of the Austrian
      states we could introduce and organize the 1st scientific institute in literature
      for neuro-rehabilitation and -prophylaxis. 80% of the neuro-rehabilitation
      patients are geriatrics. Hence overlapping of neuro-rehabilitation with
      rehabilitation in old age is to be postulated. "Rehabilitation of old age groups"
      as well has been named by us for the 1st time in scientific literature. Moreover
      we operate such activities on a large scale within a practical and social medical
      context. As worldover (at least within the civilized countries of high standards)
      the problem of old age groups is a steadily increasing and important, we are
      working on a very important scientific sector. Our slogan: "Holistic and
      permanent" is practically operated as follows: 1. Fluent transition of
      rehabilitation-adequate acute treatment towards a systematic specialized
      rehabilitation. 2. Schooling of relatives and follow up rehabilitation service.
      3. Introducing rehabilitative thoughts as well in university, teaching as (by
      separate schoolings) within medical profession and all the other health
      professions. 4. We emphasize a plurality of methods; to be named here as main
      examples: integrated physiotherapy as well as integrated psychotherapy.
      Emphasizing more scientific values for (high age-)rehabilitation, we emphasize as
      well that it must not be banned into "high age ghettos". Contrarely
      rehabilitation adapted thinking must be integrated within all the health
      professions. 5. Innovation, phantasy and pleasure must be introduced into our
      work. We report of work with lay-groups, animal-visits, hippo-therapy, music,
      etc. This forms a large interesting territory for an upraising young generation
      in health professions.

PMID- 8571603
TI  - Money is not evil.

PMID- 8571604
TI  - Infant dehydration.

PMID- 8571605
TI  - Selected topics in exercise stress testing.
AB  - More than ever before, exercise stress testing (EST) has become a focus for
      primary care physicians. But there are definite indications and contraindications
      for EST administration. Criteria may include when cardiology referrals should be
      made and what role the family physician should play in follow-up with coronary
      artery disease patients. There also are considerations for using EST for
      individuals with atypical chest pain or with patients after bypass surgery,
      angioplasty, or the coronary artery disease diagnosis. There even are distinct
      criteria for administering EST to women. This article will attempt to examine the
      numerous factors surrounding EST's growing use by primary care physicians.

PMID- 8571606
TI  - Thrombocytopenia and pancreatic carcinoma.
AB  - More and more physicians are finding increasing evidence of carcinoma-related
      immune-mediated platelet destruction. Such is the case of the patient with
      carcinoma of the exocrine pancreas associated with profound thrombocytopenia that
      follows. The patient died before studies could be completed. However, well
      recognized causes of drug reactions, DIC, chemotherapy and marrow infiltration
      were able to be excluded. Although anti-platelet antibodies weren't isolated in
      the serum, the patient's response to steroids and its similarity to other cases
      with evidence of carcinoma-related immune-mediated platelet destruction makes
      this process most likely in the case presented.

PMID- 8571607
TI  - Desire and efforts to quit smoking among cigarette smokers in Wisconsin.
AB  - This research studied the desire and attempts of cigarette smokers in Wisconsin
      to quit smoking. Data were based on the 1993 Wisconsin Division of Health's
      Behavioral Risk Factor Surveillance System (BRFSS). Among the 23% of respondents
      who were current smokers, 79% said they wanted to quit smoking and 60% said they
      had quit smoking for a day or more in the preceding year. High rates of wanting
      to quit and having tried to quit were found in all demographic subgroups of
      smokers studied. Compared to lighter smokers, heavy cigarette smokers (20 or more
      cigarettes per day) were less likely to have tried quitting in the past year, but
      were almost as likely to want to quit. These results demonstrate the great demand
      for smoking cessation services among smokers in Wisconsin and support for efforts
      to increase the use and effectiveness of these interventions.

PMID- 8571608
TI  - Compliance with Wisconsin Statute 134.66 regulating cigarette vending machines,
      Wood County, Wisc, 1993-95.
AB  - Vending machines are a significant source of cigarettes for youth. The purpose of
      this study was to determine if retailers with cigarette vending machines on their
      premises are complying with Wisconsin law designed to prevent youth from
      purchasing. Three cigarette vending machine site inspection surveys were
      conducted in Wood County during the period of 1993 to 1995. Results of the three
      site inspections showed that 4%, 29% and 15% of machines were in complete
      compliance with Wisconsin law. The most common reason for non-compliance was the
      lack of an appropriate warning sign. It is recommended that vending machine
      compliance data be included in future undercover buying operations, and suggested
      that the only vending machine regulation that can prevent youth access to
      cigarettes is one that bans cigarette vending machines.

PMID- 8571609
TI  - Wisconsin public opinion regarding clean indoor air policies.

PMID- 8571610
TI  - TQM & CQI: practice panacea or just another bowl of alphabet soup?

PMID- 8571611
TI  - Medical staff bylaws are violated by hospital's ICU restrictions.

PMID- 8571612
TI  - The Hanlester decision: intent is significant in anti-kickback law analysis.

PMID- 8571613
TI  - Wisconsin Medicaid managed care expansion: background and implications.

PMID- 8571614
TI  - Auscultation of the fetal heart presents advantages over electronic monitoring.
AB  - Currently available data support the conclusion that within specified intervals,
      intermittent auscultation of fetal heart sounds is equivalent to continuous
      electronic fetal monitoring (EFM) for detecting intrapartum fetal compromise. One
      of the disadvantages of EFM is its associated increase in cesarean delivery
      rates. Patients should receive information on both intermittent auscultation and
      EFM to enable them to make an informed choice of method for intrapartum fetal
      assessment. Presently, EFM is routinely used with the majority of laboring
      patients in the United States. This is likely due to confusion regarding the
      proper technique used for intermittent auscultation as well as insufficient
      information about appropriate interventions in the event fetal bradycardia
      occurs. We have developed a protocol for the performance of intermittent
      auscultation, including recommended responses to different levels of bradycardia.
      Intermittent auscultation is simple, provides objective information, and appeals
      to many well-informed patients. In addition, when the collection of information
      not relevant to management decisions is eliminated, intermittent auscultation
      nursing requirements are not greater than with EFM. Laboring patients should
      receive information on both intermittent auscultation and EFM to enable them to
      make an informed choice of method for intrapartum fetal assessment.

PMID- 8571615
TI  - High dose methotrexate infusion with leucovorin rescue for treatment of ectopic
      pregnancy.
AB  - The purpose of this article is to evaluate the effectiveness, side effects, and
      complications of high dose methotrexate infusion with leucovorin rescue in select
      patients with ectopic pregnancy. Between January 1991 and November 1994, 28
      patients with ectopic pregnancies were prospectively treated with methotrexate
      (100 mg/m2 intravenous bolus followed by a 200 mg/m2 infusion over six hours)
      with leucovorin rescue. Twenty-seven of 28 patients (96%) were successfully
      treated. Only one patient (4%) required a second course of methotrexate to reach
      a normal hCG titer. One patient failed methotrexate infusion 45 days after
      treatment at a hCG titer of 12 mIU/mL. No Gynecologic Oncology Group grade 3 or 4
      clinical, biochemical or hematologic toxicities occurred. Uterine bleeding and
      abdominal pain, not requiring transfusion or hospitalization, occurred in 71% and
      56% of patients. The authors conclude that high dose methotrexate infusion with
      leucovorin rescue is a highly effective, well tolerated, nonsurgical treatment
      for select patients with ectopic pregnancy.

PMID- 8571617
TI  - Proceedings of the 1995 Wisconsin Primary Care Research Forum. Wausau, Wisconsin,
      September 29-30, 1995.

PMID- 8571616
TI  - The time has come for the medical management of ectopic pregnancy.

PMID- 8571618
TI  - Behavioral risk factors of cardiovascular disease: a study of the citizens of
      Franklin, Wisconsin.

PMID- 8571619
TI  - An assessment of prehospital provider needs in Wisconsin.
AB  - The Emergency Medical Systems Advisory Board assessed via questionnaire the needs
      of Wisconsin prehospital providers. Overall, 323 out of 453 (71.3%) of the
      services responded to the query. Intermediate and paramedic services were more
      likely to respond than those prehospital providers offering basic services. Of
      the respondents, however, 235 (72.8%) identified their service as basic. In
      addition to providing information about service characteristics, each responding
      provider also rated its perceived needs. All prehospital providers, regardless of
      service level, ranked "lack of medical director" as the issue of greatest
      concern. Continuing on, intermediate and basic providers rated difficulty in
      recruiting new staff as the second greatest need. Paramedic providers, however,
      identified dispatching as their second greatest need. Rural providers rated
      difficulty in recruiting new staff and difficulty in collecting ambulance fees as
      their second and third greatest needs, respectively. Urban providers, meanwhile,
      indicated difficulty in collecting ambulance fees and access to local training as
      the second and third top needs, respectively. With the proposed new curriculum
      for basic EMT services, the needs for local medical direction will be even
      greater.

PMID- 8571620
TI  - Seven reasons for Wisconsin physicians to oppose proposed legislation to legalize
      physician-assisted suicide.

PMID- 8571621
TI  - Stark self-referral rules burdened with complexities.

PMID- 8571622
TI  - Female medical students outnumbering men; medical schools seeking more female
      faculty, mentors.

PMID- 8571623
TI  - Wisconsin women have a long history in medicine.

PMID- 8571624
TI  - [Preclinical management of the emergency by the established physician].
AB  - Within a short time, acute diseases and injuries may alter the vital functions so
      much that the life of the patient is endangered. Undisturbed consciousness,
      breathing, and circulation are the requirements for a proper organ function. The
      task of the first treating physician is to recognize and avert the acute threat
      to the patient's life and to bridge the time until qualified help arrives. The
      physical examination in emergency medicine has to be based on a few findings
      acquired at a short time. The symptoms of the acute threat can be divided in
      dysfunctions of breathing, circulation, and consciousness as well as symptoms of
      their failure. According to the emergency diagnosis, the necessary first aid
      techniques have to be applied. In this context, the cardiac arrest plays a
      particular role as an extreme special case of an emergency situation. The
      necessary steps are demonstrated as well as the decision to stop the
      resuscitation. An emergency box, which includes all drugs and equipment for the
      first aid, is desirable for the emergency treatment. The rescue line can only
      work if the general practitioner agrees to take on the role as a medical
      emergency therapist.

PMID- 8571625
TI  - [Hemorrhage from the ORL area].
AB  - Bleeding in the ENT area necessitates fast action to recognize and to stop the
      bleeding as well as to avert upcoming dangers. Prerequisite for a diagnostic is a
      good source of light via the reflector or the endoscope. During bleeding from
      wounds in the ears, nose, and throat, additional sources of bleeding from the
      mentioned cavities have to be excluded. Beside a traumatic caused bleeding, this
      finding may also be due to tumors and infections. An admixture of liquor can be
      seen during bleeding from head injury. Bleeding from the nose is located in 80%
      of the cases in the frontal part of the nose (locus Kiesselbache). A submucosal
      hematoma on the pharyngeal fornix and back wall, respectively, points to a
      fracture of the sphenoid or ethmoid bone. A blue-red colored tonsil with a fresh
      bleeding from mucosal chaps is seen as a warning indication of a tonsillogenic
      arrosion bleeding. Bleeding from the hypopharynx and the larynx necessitate the
      endotracheal intubation. Bleeding from the ear do not have to lead to rushed
      actions.

PMID- 8571626
TI  - [The psychiatric emergency].
AB  - The psychiatric emergency is primarily treated by the general practitioner.
      Particular treatments are prepared which are applied in characteristic syndromes.
      Basic psychopharmacological and legal knowledge needs to be renewed in a regular
      manner.

PMID- 8571627
TI  - [Acute therapy and prevention of ischemic cerebral infarct].
AB  - The acute therapy of the cerebral infarct necessitates the fast evaluation of the
      favorable risk factors and the assessment of its pathogenetical mechanisms to
      facilitate a specific treatment as early as possible. Acute treatment procedures
      like the rheologic therapy, anticoagulation, thrombolysis, application of calcium
      antagonists, and antiedematous therapy are discussed. Recommendations for the
      secondary prophylaxis with drugs like acetylsalicylic acid or triclopidine after
      transitory ischemic attacks or manifest brain infarctions are given. The
      indications for the surgical therapy of stenoses of the extracranial vessels
      supplying the brain are discussed and rules for the emergency management of the
      transitory ischemic attack are introduced.

PMID- 8571628
TI  - [Death or uncertain cause].
AB  - The unclear case of death usually occurs suddenly and unexpectedly, but can
      mostly be attributed to a underlying disease which was unknown during the life
      time of the patient. A reduction of mortality might be achieved by improved
      preventive measures and early treatment. During the last years, the sleeping
      apnea syndrome as an example turned out to be a considerable risk factor for
      cardiovascular diseases and accidents. Nevertheless, very many patients exist
      with an unrecognized sleeping apnea syndrome and are in urgent need of therapy.
      At first, unclear cases of death in the area of internal medicine can mostly be
      solved by an autopsy. Autopsy results are demonstrating that only one of three
      pulmonary embolism has been recognized clinically. The correct diagnosis for an
      unexpected death in the area of internal medicine could be almost ever found by a
      more careful differential diagnosis; only a few cases of death remain unclear
      after optimal diagnostics. At first, one has to think of a pulmonary embolism,
      cardiac arrhythmias or myocardial ischemia when a sudden death has occurred.
      Additionally, a pneumothorax, an alimentary bolus or an asthma attack may cause
      death unexpectedly. Metabolic dysfunctions, poisoning or a ruptured aortic
      aneurysm are often not recognized as the cause of death if it is not especially
      looked for.

PMID- 8571629
TI  - [Splenic rupture in infectious mononucleosis].
AB  - A 22 year old male with infectious mononucleosis, who stated a history of trauma
      to his left thoracic wall, developed an acute abdomen with symptoms of shock. A
      ruptured spleen was suspected. This working diagnosis, which was supported by
      ultrasound led to a splenectomy the initial diagnosis. The case report of this
      rare complication--due to the increased vulnerability of the spleen capsula in
      infectious mononucleosis--is highlighting the possible danger of splenic rupture.
      As of today, emergency splenectomy without any compromise ist still the safest
      state of the art therapy.

PMID- 8571630
TI  - [Injuries to the external male genitals].
AB  - Genital injuries are rare in comparison to other traumatologic injuries.
      Diagnostic and therapy demand a detailed urological knowledge and high abilities
      in the surgical and the microsurgical field. The emergency doctor/urologist, who
      firstly treats the patient, decides about the therapeutic outcome. Delays in the
      diagnostic procedures and false therapeutic indications may be followed by
      impairments in cosmetic and function of the genitale for the patient. Therefore,
      we demand an early consultation of an urologist.

PMID- 8571631
TI  - [50-year-old patient with dyspnea, dizziness, palpitations and brief sensory
      aphasia].
AB  - After a syncope, a 50 years old female patient was administered with an
      incomplete central facial paralysis on the left side combined with dyspnea,
      tachycardia, and hypotension as well as a systolic nurmur over the tricuspid
      valve. One week before, a vein stripping of the left long saphenous vein had been
      undertaken. By doppler-ultrasound, a thrombosis of the left tibial veins could be
      found as the cause of the pulmonary embolism. Additionally, the echocardiogram
      showed a relative tricuspid insufficiency and a floating atrial septum combined
      with an enlarged right atrium as an expression of the pulmonary hypertension. The
      incomplete central facial paralysis must be due to a paradox embolism in the
      cerebrovascular circulation as a result of an open foramen ovale. Under a therapy
      with high-dose heparin, all findings receded totally within one week.

PMID- 8571632
TI  - [Blood specimen collection from central venous catheters--reliable also for blood
      coagulation analysis?].
AB  - Blood probes obtained from the central-venous catheter are common methods on
      intensive care units. In the present paper, the conditions for obtaining blood
      samples for clotting analysis of patients with heparinized catheters are examined
      and compared to the literature. In these patients, blood samples were drawn
      simultaneously from central as well as peripher lines. The results of the
      examination were prospectively compared. After the aspiration of 10 ml blood from
      centralvenous catheters, there are no differences between peripher and central
      venous blood samples.

PMID- 8571633
TI  - [Pharmacologic principles of drug prescribing in pregnancy].
AB  - The administration of drugs to pregnant women comprises special problems. This
      review gives an overlook on changes in the pharmacocinetics due to pregnancy and
      on the possible side effects of drugs on embryo and fetus. Finally, general rules
      for the prescription of drugs to pregnant women are given.

PMID- 8571634
TI  - [Prevention, standards and future developments in medical specialties-
      prevention].

PMID- 8571635
TI  - [From expert testimony general practice: in fronto-basal skull fracture surgical
      evaluation is required].

PMID- 8571637
TI  - [Saxony training program for cardiopulmonary resuscitation].

PMID- 8571636
TI  - [Emergency service course manual--a contribution to quality assurance in
      emergency medicine education].
AB  - For the purpose of comparison and quality control for the acquisition of the
      subspeciality in emergency medicine, a committee of experts in the area of
      emergency medicine developed the first curriculum (course book Emergency
      medicine) valid in all states of Germany. The requirements for the development of
      this curriculum were derived from the experts' experiences and from the
      requirements of the medical society for the quality of medical training.

PMID- 8571638
TI  - [Sleep apnea and cardiovascular risk].
AB  - Obstructive sleep apnea syndrome (OSAS) is the most important form of sleep
      related breathing disorders due to its high prevalence and its potential for
      developing cardiovascular diseases. The increased morbidity of these patients is
      explained by the coincidence with cardiovascular diseases, and the increased
      mortality of untreated patients is due to cardiovascular complications, which
      depend on the degree of the breathing disorder. Heavy snoring, as a partial
      obstruction of the upper airways, and OSAS are independent risk factors for the
      development of cardiovascular diseases and stroke. Causal associations exist
      between acute hemodynamic changes, pressure and volume load, changes in the
      humoral and the central nervous system, and blood gas alterations during the
      obstructive apnea and the long-term condition due to OSAS. Obstructive apnea can
      be divided into an early phase, a late phase, and a phase of the postapneic
      hyperventilation with respect to hemodynamic changes, blood gas alterations, and
      the autonomic nervous system. The most striking changes in these parameters are
      seen at the end of apnea and in the first resumption of breathing, with an
      increase in systemic and pulmonary blood pressure, decrease in stroke volume, and
      a distinct change in heart rate. Manifestation of systemic hypertension even in
      the awake state is promoted by changes in the volume system, with activation of
      neurohumoral changes and by a resetting of baro- and chemoreceptors. Similar
      mechanisms are discussed in the development of pulmonary hypertension. In this
      circumstance the role of hypoxemia as a causal factor for pulmonary hypertension
      or as a consequence due to structural changes of the pulmonary vessels is
      controversial. OSAS is frequent in patients with coronary heart disease and these
      patients must be classified as a particular risk group because of apnea
      associated silent myocardial ischemia and electric instability of the myocardium.
      The occurrence of arrhythmia in patients with OSAS is closely related to the
      apnea and hyperventilation events and depends on the sympathovagal balance. Early
      diagnosis and suitable therapy of patients at risk not only abolishes the sleep
      related breathing disorder but also improves long-term outcome.

PMID- 8571639
TI  - [Occupational rehabilitation after percutaneous transluminal coronary angioplasty
      (PTCA)--correlation with subjective and objective parameters].
AB  - On the basis of medical criteria percutaneous transluminal coronary angioplasty
      (PTCA) is followed by only a short interval of work inability. This study
      evaluated the interval between PTCA and the return to work and the factors which
      may influence this interval. The study included 122 working patients with
      angiographically successful PTCA. Patients were followed up clinically and
      angiographically and completed a standardized questionnaire directly after PTCA
      and 4 months later. The study population comprised 87 patients (81 men, 6 women)
      who filled out both questionnaires appropriate for evaluation. Of these 48 (55%)
      had single-vessel, 27 (31%) two-vessel, and 12 (14%) three-vessel disease.
      Complete revascularization in terms of treatment of all lesions above 70% was
      achieved in 85 (98%) patients. In 30 (34%) patients restenosis developed during
      the observation period as evaluated by coronary angiography. At the time of the
      second evaluation 46 (53%) patients complained of persisting or new thoracic
      pain, which they understood as cardiac pain. After 4 months 68 (78%) patients
      returned to work, 12 (14%) were on sick leave, 3 (3%) were unemployed, and 4 (5%)
      were retired. The median of time on sick leave after PTCA was 14 days. The length
      of sick leave after PTCA was found to depend significantly on the previous
      intention to retire (25% vs. 75%, p < 0.01). Patients who did not return to work
      during study period reported more frequently of thoracic pain (55% vs. 45%, p =
      0.01) and had less intention to return to work after PTCA (6% vs. 94%, p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8571640
TI  - [Noninvasive evaluation of the patency of coronary vessel stents using electron
      beam tomography segment images with administration of contrast media].
AB  - The implantation of intracoronary stents is increasingly employed in
      interventional cardiology. Even with high-resolution x-ray equipment the tiny
      struts of stainless steel stents can usually not be visualized. Coronary
      angiography is required to prove stent patency, and correct localization and
      deployment of the stent can only be assessed with intravascular ultrasound. In
      this setting a non-invasive diagnostic method would be of great advantage to
      document patency of the stented vessel segment. Herein we describe two patients
      with stent implantation in whom contrast-medium-enhanced electron beam
      tomographic scanning was applied to check for vessel patency. A pathological
      finding with reduced contrast enhancement could be distinguished from a normal
      finding, as was confirmed subsequently as a highly obstructed and a patent
      stented vessel segment by angiography. Thus, for the first time an alternative
      non-invasive diagnostic method may provide information on patency of stented
      vessel segments and may be useful for sequential follow-up investigations.

PMID- 8571641
TI  - [Pharmacologic myocardial protection during percutaneous transluminal coronary
      angioplasty (PTCA) by intracoronary dipyridamole: hemodynamic, contractile and
      dynamic ventricular consequences].
AB  - Percutaneous transluminal coronary angioplasty (PTCA) represents a suitable model
      to establish myocardial ischemia in man. Balloon inflation usually is accompanied
      by a significant deterioration in left ventricular systolic and diastolic
      properties. A brief episode of ischemia followed by reperfusion termed
      preconditioning has been identified as a mechanism rendering the myocardium more
      resistant to ischemia. Adenosine is considered as important mediator of
      preconditioning. Dipyridamole represents an important drug interfering with
      myocardial adenosine metabolism by inhibiting its cellular reuptake. The aim of
      this study was to investigate if an intracoronary infusion of dipyridamole
      represents a suitable tool in preventing the deterioration of left ventricular
      performance and hemodynamics during PTCA. In 20 patients undergoing elective
      coronary angioplasty of a major vessel assessment of angiographic left
      ventricular performance and left ventricular hemodynamics was performed before,
      during and after coronary angioplasty. Patients were randomly allocated to study
      group 1 receiving an intracoronary infusion of dipyridamole prior to PTCA and
      study group 2 where conventional pretreatment was performed. In study group 3
      intracoronary dipyridamole infusion was performed in 10 patients with coronary
      artery disease during coronary angiography in order to evaluate its effect on
      baseline hemodynamics and left ventricular performance. Dipyridamole-pretreatment
      resulted in a significant preservation of systolic and diastolic left ventricular
      performance during PTCA, as documented by an uneffected global ejection fraction
      (in comparison to a deterioration of 29.2% in study group 2) and an increment in
      diastolic stiffness of only 12.7% (in comparison to an increment of 57.3% in
      study group 2). Furthermore, a significant prolongation of achievable balloon
      inflation times of 48.4% could be obtained in study group 1. In addition,
      incidence of arrhythmias seemed to be reduced in study group 1. Apart from two
      cases of coronary steal phenomenon no significant side effects of dipyridamole
      infusion could be detected. Finally, in study group 3 dipyridamole-pretreatment
      per se induced a significant amelioration of angiographically assessed left
      ventricular systolic performance.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8571643
TI  - [Surgical therapy of acute tricuspid valve endocarditis: indications, technique
      and results].
AB  - Tricuspid valve endocarditis is treated by antibiotics alone in the majority of
      the cases. However, intractable infection or hemodynamic compromise may warrant
      surgery. In those cases total valve-excision or valve-replacement had been the
      most common surgical procedures. Both are controversial in regards to the
      hemodynamic consequences and to the long-term prognosis. In the following,
      results of tricuspid valve repair in acute infective endocarditis are reported
      and discussed as an additional treatment option. Between January 1988 and
      December 1993, 118 patients were operated for acute valve endocarditis at our
      institution. Eleven of these patients had tricuspid valve endocarditis, isolated
      (n = 7) or combined with endocarditis of a left-sided valve (n = 4). In the cases
      with isolated tricuspid valve endocarditis, the indication for surgery was
      intractable infection in 6 and hemodynamically relevant tricuspid-insufficiency
      in 1 out of 7 patients, respectively. In all patients with associated left-sided
      endocarditis, the indication was hemodynamic deterioration. In 8 patients the
      tricuspid valve endocarditis was treated as follows: Debridement, vegectomy,
      patch-reconstruction of the cusps, bicuspidalization. In 3 patients
      reconstruction was not possible because of extended involvement of all parts of
      the valve, including the valve ring and the papillary muscles. In these patients,
      primary valve-replacement (n = 1) or valve-excision with secondary replacement (n
      = 2) was performed. In 4 patients tricuspid-reconstruction was combined with
      mitral- (n = 1), aortic- (n = 1) or double-valve replacement (n = 2).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8571644
TI  - [Stress reaction of pulmonary artery pressure in the early and chronic phase
      after heart transplantation: comparison with healthy control probands].
AB  - The pulmonary artery pressure response to exercise frequently reflects
      ventricular diastolic properties. The aim of this study was to determine
      noninvasively cardiac allograft function and pulmonary artery pressure response
      to stress in the early and late phases after heart transplantation (HTX). Ten
      patients in the early postoperative phase (3.7 +/- 1.6 months postoperatively,
      group I) and ten patients at least 2 years after HTX (34.3 +/- 8.3 months
      postoperatively, group II) were studied by two-dimensional (2 D-), M-Mode, and
      Doppler echocardiography during supine graded bicycle exercise (25, 50, 75, 100
      watts). The patients' data were compared to those obtained in eight normal
      controls. The peak pressure gradient between the right ventricle and right atrium
      during systole was derived from saline contrast-enhanced Doppler echocardiography
      of the tricuspid regurgitant jet and used as an estimate of pulmonary artery
      systolic pressure. In group I- and group II-patients, resting and exercise left
      ventricular diameters as well as systolic function were normal. The right
      ventricle was enlarged (3.2 +/- 0.4 cm/3.0 +/- 0.6 cm in group I/group II versus
      2.1 +/- 0.3 cm in normal controls, p < 0.05). During exercise, heart rate
      increased less in heart transplant recipients (+26%/+36% in group I/group II, p <
      0.05) than in normals (+67% at 100 watts, p < 0.05). Resting pulmonary artery
      pressures were similar in heart transplant recipients in the early and late
      postoperative stage and in normals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8571642
TI  - [Inpatient length of stay and physical capacity after aortocoronary bypass
      operation, after heart valve replacement and myocardial infarct].
AB  - The present investigation was performed to determine the dependence of the length
      of stay in community hospitals and rehabilitation clinics from patient
      characteristics and physical activity at the end of treatment. Comparing age, end
      diastolic volume index, left ventricular ejection fraction, number of stenosed
      coronary arteries, number of bypass grafts, levels of physical exercise, body
      mass index and the ratio total cholesterol/HDL-cholesterol, no significant
      differences were found in patients, who reached the rehabilitation clinic in the
      early postoperative period (7.4 +/- 2.0 days, n = 98), after 15-28 days (n = 74)
      or later than 28 days (n = 156) after bypass-surgery. Similar results were
      observed in 103 patients after heart-valve replacement, who arrived at the
      rehabilitation clinic after a corresponding length of hospital care like the
      bypass patients. Also, no significant differences in the clinical characteristics
      and physical activity appeared in patients who were admitted in the early phase
      (9.2 +/- 4.5 days) after transmural myocardial infarction (n = 37) and those
      entering the rehabilitation clinic after 26.7 +/- 9.4 days of hospital stay (n =
      32). The absence of any relationship between the length of stay in hospitals on
      the one hand and severity of the heart disease on the other hand points out that
      the whole duration of stay in community hospitals and rehabilitation clinics
      after surgical intervention and also after transmural myocardial infarction could
      be drastically shortened by an optimal cooperation of both, hospitals and
      rehabilitation clinics, without any impairment of clinical results.

PMID- 8571645
TI  - [Intramural hemorrhage of the thoracic aorta as a precursor of dissection].
AB  - Aortic dissection without entry and blood-flow in a false lumen was recently
      identified at necropsy and in vivo as intramural hemorrhage in the aortic wall
      (IMH). It was the purpose of the study to elucidate clinical signs and prognosis
      in this rare and poorly understood condition. Among 360 prospectively evaluated
      patients with clinical suspicion of aortic dissection, 195 patients presented
      with evidence of aortic disease. Of these, 25 patients (13.2%) had IMH of the
      thoracic aorta with no primary intimal tear, flap or overt dissection as shown by
      MRI (n = 12), contrast enhanced CT (n = 14) and TEE (n = 3). IMH was confirmed
      intraoperatively or at necropsy. There were 16 men and 9 women of ages 56 +/- 13
      years; arterial hypertension was associated in 84% and Marfan's syndrome in 12%.
      IMH involved the ascending aorta in 12 (48%), the arch in 2 (8%), and the
      descending aorta in 11 cases (44%). IMH occupied 8.5 +/- 5 cm in length and 2.0
      +/- 1.2 cm in aortic wall thickness. Both aortic regurgitation and
      pericardial/mediastinal effusion was present in 42% of type A and in 18% of type
      B IMH. IMH progression to overt dissection, rupture and/or acute tamponade
      occurred in 8/25 cases (32%) within 24 to 72 h, indicating the need for urgent
      surgical repair. The 30-day mortality of IMH inflicting the ascending aorta was
      80% (4 of 5) with medical treatment in contrast to none (of 7) with early
      surgical treatment (p < 0.01). One-year survival was 71% in surgically treated
      patients and 20% with medical treatment (p < 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8571646
TI  - [Q-fever associated myocarditis in a 14-year-old boy].
AB  - A 14-year-old boy presented with the symptoms and clinical signs of myocarditis.
      Ventricular arrhythmias were the main manifestation. Dilated left ventricle with
      slightly impaired contractility and spongy appearance of the myocardium were also
      noted. Laboratory signs of an acute infectious disease were absent, but a
      significant rise in the complement fixation titer for Coxiella burnetii was
      observed. Treatment with oral tetracycline for 6 months resulted in improvement
      of ventricular arrhythmias and normalization of left ventricular dimensions and
      structure over the following months. Cardiac involvement in Q fever is rare, and
      with it endocarditis is usually seen as a chronic form of the disease.
      Myocarditis associated with Q fever has been reported only in some rare cases but
      not in children. The case reported here illustrates that the diagnosis of Q fever
      should also be considered in a case of myocardial involvement in an infectious
      disease of unknown etiology.

PMID- 8571647
TI  - [11th report of the structure and performance of heart catheterization
      laboratories in Germany. Results of a survey by the Committee of Clinical
      Cardiology of the German Society of Cardiology--Heart and Cardiovascular Research
      1994].

PMID- 8571648
TI  - [Biomechanical principles in diarthroses and synarthroses. IV: the mechanics of
      lumbar vertebrae. A pilot study].
AB  - Theoretical considerations help define the requirements for an apparatus that is
      to localize the instantaneous helical axes (IHA) of axial rotations of lumbar
      segments. RESULT: Since the range of axial rotation of an L3/4 segment is in only
      approximately +/- 1.5 degrees the rotational angle intervals have to be smaller
      than 0.3 degree with an resolution less than 0.03 degree in order to be able to
      determine the loci of the IHAs. For the first time in vitro measurements are
      presented that satisfy this requirement. The data prove that the guidance by the
      artt. zygapophysiales critically influence the possible positions of the IHA.
      Comparatively, ligaments and intervertebral disk play a marginally role. During
      axial torques Tz the IHAs lie dorsal to the intervertebral disk and migrate from
      one joint to the other depending on axial rotation (length of migration:
      approximately 3-4 cm). The IHAs lie almost parallel to the axial torque vector.
      When the joints are removed the IHA is stationary and almost perpendicular to the
      intervertebral disk and intersects the disk's central region. The screw
      inclination (pitch) of the instantaneous screw movement is proportional to the
      rotational angle. Therefore, depending on the direction of rotation, one obtains
      left or right handed screw movements. This means: axial torsional load leads to
      an increase in thickness of the intervertebral disk. During preloads that
      produces extensions the fixed centrodes (paths of axis migration) of intact
      segments are dorsally beaten out, whereas during flexional loads they are
      ventrally beaten out. Then, the IHAs migrate through the canalis vertebralis. By
      the concept "dimeric link chain" the different shapes of the fixed centrode are
      traced back to the morphology of curvature of the articulating surfaces. The
      measurements suggest the hypothesis that the distinct nonlinearity of the load
      displacement curves (s-shape of alpha = alpha (Tz) funktion is an affection of
      IHA migration. Comparatively, the influence of ligaments can be neglected. The
      measurements suggest the hypothesis that the hysteresis of the load displacement
      curves (neutral zone) is an artefact that does not appear in vivo. Altogether,
      the experiments prove that the loci of the IHAs are determined by the interplay
      of preload, structure of the applied force system and morphology of curvature of
      the articulating surfaces. By that the possibility is clinically given to
      calculate the multitude of possible movements as function of muscle activity when
      in the individual the shape and the position of the articulating surfaces are
      measured in vivo (by NMR-methods e.g.). A physically based classification of
      pathological cases seems to be possible.

PMID- 8571649
TI  - [Virtual reality in orthopedics: principles, possibilities and perspectives].
AB  - Virtual Reality is a new form of human-machine interface. Virtual Reality
      integrates the human into the virtual world of the computer. Concerning existing
      Virtual Reality programs and 3D-graphics in medicine this article shows
      possibilities and perspectives for orthopedic surgery. Using Virtual Reality the
      orthopedic specialist is able to improve the diagnosis, the planning and
      supporting of operations just as new ways of teaching and training. Virtual
      Reality (VR) assists disabled individuals in improving the quality of life an
      working with computers. Principles will be discussed in respect to the four
      categories Immersive VR, Desktop VR, Pseudo VR and Inverse VR.

PMID- 8571650
TI  - [Osteoneogenesis in callus and epiphyseal distraction].
AB  - X-rays were reviewed after callus distractions (50 cases) and distraction
      epiphysiolysis (10 cases) in 45 patients. With the aid of a computerized
      digitization system for analogue films, the relative x-ray density of the
      distraction area was determined in the medial, lateral, ventral and dorsal
      surface areas, and in the median line of the callus tissue. Bone formation became
      evident within 21.7 +/- 3.7 days post-distraction in the thigh and 25.4 +/- 4.9
      days in the shank. The lowest density values were found at the end of the
      distraction phase followed by a continual increase in x-ray density in the
      fixation phase. There was a significant decrease in callus x-ray density in the
      shank from lateral to medial and from dorsal to ventral, and in the thigh from
      medial to lateral and from dorsal to ventral. When the corticotomized callus
      distraction is compared to the distraction epiphysiolysis without corticotomy it
      becomes apparent that the differences between lateral-medial x-ray densities and
      dorsal-ventral x-ray densities were significantly greater in the group with
      callus distraction. The deminished bone formation in the ventromedial area of the
      shank and the ventrolateral area of the thigh seems to be due to soft tissue
      damage and disturbances in local bone blood supply after the operative approach
      for corticotomy.

PMID- 8571651
TI  - [Clinical relevance of the early detection of arthrosis].
AB  - In the years 1989 to 1992 615 local persons underwent yearly examinations for
      analysis of osteoarthrosis of the hip and knee by means of comprehensive
      documentation of orthopaedic health history and clinical findings. Of special
      interest in our investigation were the Altman ACR criteria for osteoarthrosis of
      the hip and knee over the years. We can show, that finding the diagnosis is as
      accurate with the ACR criteria as well as the far more extensive Lequesne and
      Tegner-Lysholm score. Analysis of the investigations over the years revealed
      clearly different results in the frequency of osteoarthrosis. The reason is the
      nature of osteoarthrosis changing between silent and active phases especially
      during time of onset. Our investigations show, that valuable criteria exists for
      detection of early osteoarthrosis, however apparent are deficits for observing
      its course.

PMID- 8571652
TI  - [Suppression of heterotopic ossification: single-dose versus fractionated
      irradiation--animal study].
AB  - Periarticular ossification is one of the main problems of total hip replacement.
      Irradiation with megavolt photons is known to be a well recognized means of
      prevention of heterotopic ossification. So far only little scientific basis
      exists about the most favourable way of radiotherapy for prevention of ectopic
      ossification. In this study two theoretically equivalent doses are compared.
      Allogeneic bone matrix was implanted into both thighs of 50 adult male Wistar
      rats for experimental induction of heterotopic ossification. Immediately after
      operation the thigh implants were irradiated with a single dose of 7 Gy or a
      total dose of 10 Gy given in 5 fractions of 2 Gy each. In the model of matrix
      induced osteogenesis in rats fractionated irradiation by 5 x 2 Gy leaded to a
      highly-significant (p = 0.001) better suppression of ectopic ossification
      compared to irradiation by 1 x 7 Gy. Once-only irradiation with 1 x 7 Gy leads to
      a reduction of the calcium contents by 27.5%, split irradiation by 5 x 2 Gy
      obtained a reduction by 66.9% compared to the calcium contents of thigh implants
      not exposed to radiation. In view of experimentally proven better effects,
      fractionated irradiation has to be preferred to single dose radiation also
      considering less side effects in split radiation.

PMID- 8571655
TI  - [Long-term results in complex knee injuries using sutures and reconstruction of
      the posterior cruciate ligament].
AB  - There is still a great discussion what's the best treatment for disruptions of
      the posterior cruciate ligament. The results of the operations are often bad. In
      Rheinfelden from 1979 to 1990 34 Patients underwent an operation of the posterior
      cruciate ligament. In 1991 we made a follow-up evaluation with 30 of these
      patients. The results according the OAK-Score were 8 x excellent, 11 x good, 3 x
      fair and 5 x poor, 3 patients were reoperated elsewhere. The average Lysholm
      score was 79 points. The results after treatment of the freshly ruptured
      ligaments were much better than the results of the treatment of chronic
      instabilities. A significant acute posterior instability should be operated.

PMID- 8571654
TI  - [Treatment results of Imhauser's method of treating neonatal clubfeet].
AB  - The results of treatment of newborn clubfoot are reported 6 years and 3 months
      after operation. 88 children with 123 clubfeet were treated beginning at the
      neonatal period with redressment and casting followed by achillotenotomy and
      dorsomedial and dorsolateral capsulolysis of the talocrural and talocalcaneal
      joints at 4 to 7 months of age. After that a strict protocol of physiotherapy,
      orthetics and controlling was used. For clinical and radiological assessment the
      criteriasof Magone (40) and Simons (51, 52) were used. The significance of
      parental cooperation was analysed. At follow-up the result was good or acceptable
      in 83.7% according to clinical findings and 43.6% according radiology
      respectively. There was obviously no correlation of clinical and radiological
      findings. The mobility of the ankle joint proved to be important regarding the
      functional result, especially in cases with flat-top-talus it has been limited.
      Parenteral cooperation is of special importance for good results in clubfoot
      therapy.

PMID- 8571653
TI  - [Use of lasers in orthopedic surgery--a mutagenesis risk?].
AB  - Since ten years different laser systems have been used in arthroscopic procedures
      and percutaneous laser disc decompression. A potential mutagenic risk has not
      been excluded yet. From photobiology it is known that light in the UV-range is
      the main source of mutations. Therefore the aim of our study was to determine the
      mutagenic risk of laser systems at UV-wavelengths. The BALB/3T3 cell line was
      irradiated at the Excimer wavelengths 248 nm and 308 nm. Transformation rates
      were compared with non-irradiated cells and the effect of 1 Gy-Roentgen
      irradiation. Pulse energy, frequency and irradiation time were varied over a
      broad range. The effect of double irradiation was also examined. For 308 nm no
      significant transformation rate was found (p < 0.18). In contrast 248 nm showed a
      highly significant transformation rate (p < 10(-9). Transformation rate after
      Roentgen irradiation exceeded that of the negative control about two orders.
      While a certain mutagenic risk exists for 248 nm application of the wavelength
      308 nm seems harmless. Our data therefore represent an essential contribution to
      long term laser safety both for the physician and his patient.

PMID- 8571656
TI  - [Modification of patella alta, patella ventralization en patella lateralization
      in patellar pain syndrome following implantation of total GSB endoprosthesis].
AB  - We examined the degree of retropatellar pain related to biomechanical factors of
      the implantation in 31 cases of GSB-endoprostheses without retropatellar
      alloarthroplasty, loosening or infection. Postoperative patella alta and
      lateralisation of the patella extended the retropatellar pain syndrom but not
      tibiaventralisation. These results indicate that certain unfavourable patella
      positions may be responsible for the retropatellar pain syndrom in patients with
      a GSB-endoprosthesis.

PMID- 8571657
TI  - [Hip screening in children. Comparison of various ultrasonographic methods].
AB  - 750 Hips of 375 babies under 5 months were sonographically examined. We used the
      procedures following Graf and Suzuki and compared the methods and the results.
      The authors suggest that the ultrasound study following Graf provides more
      advantages and today is the best procedure in the screening of hip dislocation.

PMID- 8571658
TI  - [Conservative and surgical early treatment of congenital femoral dysplasia and
      defects to obtain early normal growth].
AB  - In three children with proximal femoral focal deficiency arthrography of the hip
      joint was performed at age 9 days, 4 and 5 weeks. Between the unossified part of
      the femoral neck and the cartilaginous femoral head there was a moderate
      flexibility in the first child and a lysis with some displacement of the femoral
      neck in the other two. After immobilisation in a squatting cast for 3 months
      consolidation was achieved and the growth plate developed normally. Coxa vara and
      retrotorsion was marked in all children. The earlier they were treated by valgus
      osteotomy and rotation to normal anteversion, the earlier normal growth started.
      Therefore early diagnosis, conservative and operative treatment is indicated in
      these children. Femoral lengthening is necessary then for only a few centimeters.
      Resection of the unossified part of the femoral neck is not indicated.

PMID- 8571659
TI  - [Cementless cup anchorage in hip endoprostheses. Comparative study of 3 cup
      systems with titanium surface].
AB  - A wealth of commercially available hip endoprotheses makes it difficult for the
      practitioner to choose the best implant for each individual case. In a multi
      centre study, in which 22 hospitals took part, a cementless stem was used 1172
      times and was combined with 3 different cementless cup components. The follow up
      period ranged from 1-8 years. In 321 cases the spherical Mecring cup, in 208
      cases the spherical CLS-expansion cup and in 643 cases the conical Weill-ring was
      implanted. The predominant indication for the THR was primary coxarthrosis (767
      patients). Evaluation of clinical results was based on the Merle d'Aubigne score.
      Good or excellent results were found in 82% for the Mercring, in 85% for the
      Weill-ring and in 91% when the CLS-expansion cup was used. Whereas 88% of the
      patients with the Mecring or Weill-ring had minimal or no pain, 94% of the
      patients had minimal or no pain when the CLS-expansion cup was implanted. Aseptic
      loosening was found in 1.25% for the Mecring and 1.5% with the Weill-ring. In the
      CLS-expansion cup group, 2 cases with radiological signs of loosening were seen,
      but neither patient required revision. The CLS-expansion-cup with the press fit
      system shows better medium follow-up results in this study, than the Mecring or
      Weill-ring systems.

PMID- 8571660
TI  - [10 years of cementless implantation of total hip endoprosthesis using
      Zweymuller's stem].
AB  - A retrospective study of the first consecutive 111 cementless Zweymuller Stems
      has been performed. 56 cases have been followed clinically and radiologically
      with an interval of 10-11 years. The average harris hip score was 90.7 pts, the
      cumulative success rate of the stem was 97.96% after 10-11 years. The frequency
      of bony reactions around the stem and their changes during the course of time
      could be followed in 40 implants with a complete radiologic documentation at 5
      and 10 years postoperative. Hypertrophic changes of the bone around the tip of
      the stem remained unchanged from the fifth to the tenth year but there was an
      increase of proximal lucencies (27% at 5 yrs, 35 at 10 yrs), widening of the
      calcar (20% at 5 yrs, 25% at 10 yrs) and stress shielding (30% at 5 yrs, 47% at
      10 yrs).

PMID- 8571661
TI  - [Strength of muscles surrounding the hip joint and gait in patients following
      implantation of a cementless hip endoprosthesis].
AB  - There are only a few studies which could support conclusions concerning the
      strength of the muscles surrounding the hip joint and especially concerning the
      strength relationships following implantation of endoprotheses. The aim of this
      study was to examine the pre- and postoperative course of strength deficits in
      this musculature compared to clinical parameters and the uninvolved side. Fifty
      eight patients between 30 and 67 years of age, in whom individual total hip
      protheses were implanted were clinically examined prior, 9 weeks and 6 months
      after surgery. Moreover, the maximum isometric strength of abductors, flexors,
      and rotator muscles as well as maximum isokinetic strength of the extensors and
      flexor musculature at 60% and 120%/s were measured. The flexor and extensor
      musculature already showed a clear increase in maximum strength after 9 weeks and
      6 months (90-124%). By contrast, the isometric strengths of the rotators
      increased only slightly, the abductor strength decreased after 6 weeks to below
      the preoperative baseline level and attained this level again only after 6
      months. The clinical parameters Trendelenburg sign, limping and walking capacity
      were clearly improved after 6 months, but no correlation to the abductor strength
      could be demonstrated. It is concluded that limp-free gait can be attained even
      without maximum strength increase in the abductors, which are important for fluid
      gait, at least for short distances. The importance of regular training of the
      rotator and abductor musculature in coxarthrosis is emphasized to delay
      limitation of movement and decreased strength in the sense of capsule pattern.

PMID- 8571662
TI  - [Preferential sites for rupture of the long head of the biceps tendon].
AB  - The extreme stress on the long head of the biceps tendon is defined by its
      specific anatomical situation with near contact to the rotator cuff, to the
      sulcus intertubercularis and to the acromion. We took 74 specimens from cadavera
      and studied the macromorphological and cross-sectional anatomy to analyze changes
      preceding rupture of the biceps tendon. Degenerative tendon alterations with
      disorganized collagen fibers and large mucoid deposits occurred especially at the
      distal sulcus bicipitalis and near the origin of the tendon at the superior part
      of the glenoid labrum. The found degenerative histological alterations are
      possibly precursor of tendon rupture near to the distal sulcus or precursor of
      the so called "SLAP"-lesions.

PMID- 8571663
TI  - [External fixators in temporary spinal stabilization. Radiographic anatomy of the
      lumbar pedicles].
AB  - External spinal fixation is used in cases where fusion is indicated and for
      reducing the number of stiffened segments in lumbar sacral pain. Owing to the
      percutaneous implantation, only the pedicle oval is available for localizing the
      screw in a-p X-rays. Cadaver studies have shown that the root of the arch and the
      halo are not identical and that unless one relies on the midpoint of the halo the
      pedicle may be perforated medially. rate, with markedly enhanced fusion of the
      lumbar spine following external spinal fixation.

PMID- 8571664
TI  - [Considerations on education and formation in health care ethics in Belgium].
AB  - Codes of medical ethics summarize the most important duties of the medical
      profession; but the field of medical ethics encompasses more problems than are
      treated in the codes, and the management of many health care problems
      necessitates the collaboration of non-medical personnel. This state of affairs
      has led to the broader notion of health care ethics. All important problems of
      health care have ethical aspects, and during the last decennia progress in many
      branches of biology and medicine has brought with it new ethical problems. This
      renders teaching and education in health care ethics all the more important. The
      time allotted to the formal teaching of health care ethics is very limited.
      Therefore, whoever is responsible for teaching and education of medical students
      should contribute by his(her) example, his(her) advice and supervision, where
      appropriate, to the ethical education of the younger generation. As new problems
      will surely arise during the later professional life, their explanation and
      discussion should, more than is currently being done, be integrated in the
      programs of continued medical education.

PMID- 8571665
TI  - [The price of quality: health care expenditures and quality of life].
AB  - In an era where the substitution of health policy by budgetary arguments is
      imminent, this paper aims to offer some elements in the discussion on the
      relationship between health care expenditures and their effect on quality of life
      for individuals and society. Historical developments, present differences in
      medical consumption and in outcome, the growing interest in alternative medicine,
      the use of new medical technologies and observations on the expenditures for
      pharmaceuticals show that this relationship is not self-evident and that
      generalizations must be avoided. The observations lead to an argument of more
      efficiency in the use of health care resources.

PMID- 8571666
TI  - Mechanism of action and thrombolytic potential of staphylokinase.
AB  - Staphylokinase is a profibrinolytic agent that forms a 1:1 stoichiometric complex
      with plasminogen that, after conversion to plasmin, activates other plasminogen
      molecules to plasmin. The plasmin.staphylokinase complex, unlike the
      plasmin.streptokinase complex, is rapidly inhibited by alpha2-antiplasmin. In a
      plasma milieu, staphylokinase is able to dissolve fibrin clots without associated
      fibrinogen degradation. This fibrin-specificity of staphylokinase is the result
      of reduced inhibition by alpha2-antiplasmin of plasmin.staphylokinase complex
      bound to fibrin, recycling of staphylokinase from the plasmin.staphylokinase
      complex following inhibition by alpha2-antiplasmin, and prevention of the
      plasminogen.staphylokinase to plasmin.staphylokinase. In experimental animal
      models, staphylokinase appears to be equipotent to streptokinase for the
      dissolution of whole blood or plasma clots, but more potent for the dissolution
      of platelet-rich or retracted thrombi. The thrombolytic potential of recombinant
      staphylokinase is presently under investigation in pilot studies in patients with
      acute myocardial infarction or with peripheral arterial occlusion. Definition of
      the therapeutic benefit of recombinant staphylokinase will require more detailed
      dose-finding studies followed by randomized efficacy studies against other
      thrombolytic agents.

PMID- 8571667
TI  - [Interleukin-6 and spinal cord damage in rats].
AB  - A new method was briefly described for microdialysis of the spinal cord in freely
      moving rats with a removable probe. The technique allowed to measure interleukin
      6(IL-6) release in the extracellular fluid of the spinal cord when the rats were
      fully recovered from the operation and while they were freely moving. The injury
      inducing effect of performing microdialysis of the spinal cord in rats was
      studied. In conclusion, long-term presence of a probe in the spinal cord causes a
      lesion which is functionally of borderline significance. The Tarlov score and the
      performance in the inclined plane test can be used as valid and reliable
      indicators of residual spinal cord function after injury in rats. Using the
      microdialysis technique, it was shown that IL-6 is secreted in injured spinal
      cord. However, we could not show that mechanical trauma induces IL-6 secretion.
      Methylprednisolone (MP), which has a known neuroprotective effect in SCI in rats,
      was administered (30 mg/kg body weight, 0.4 ml, i.v., 45 min after injury) to
      rats with a 50g static load-induced SCI. The control group received saline.
      According to a randomized, blinded protocol, the rats (n=21) were subjected to
      the inclined plant test and evaluated in open field with the Tarlov score before
      and after injury (day minus 1, days 1,2,3,4,7,14, and 21). Mortality before day
      21 was registered. In conclusion the data show that one intravenous dose of MP
      increases survival rate in rats with SCI. The data confirm that MP diminishes
      tissue damage in SCI. The present study provides evidence for an in vivo
      neuroprotective action of IL-6. The spinal cords of 42 Wistar rats were injured
      in the same way as in the previous experiment, and the evaluation of the animals
      was also the same. In conclusion, the results suggest that IL-6, locally
      administered into the spinal cord, diminishes tissue damage and augments chances
      of survival after SCI.

PMID- 8571668
TI  - [Anthelmintics resistance in gastrointestinal nematodes in domestic animals].
AB  - In Belgium benzimidazole resistance has been reported in 28% of the sheep farms
      and 29 to 50% of the studs. In several member states of the European Union the
      prevalence of anthelmintic resistance (AR) is even higher than in Belgium,
      although AR is nearly absent in some countries of Southern Europe. AR is
      particularly widespread in certain nematodes of sheep, goats and horses in
      Europe, whereas only sporadic cases of AR have been reported in helminths of
      cattle. In Belgium only one case of AR has been described in goat and one in
      cattle; no surveys for AR have been carried out in pigs. The main helminth
      species, in which AR has been observed, are Haemonchus contortus, Ostertagia
      circumcincta and Trichostrongylus spp. in small ruminants, the Cyathostominae in
      horses and Oesophagostomum spp. in pigs. Resistance has developed particularly
      against the benzimidazoles and to a lesser extent against the levamisole/morantel
      group. Up to now the prevalence of ivermectin resistance remains low, but the
      number of cases is increasing during recent years. Due to the low sensitivity of
      the currently used techniques for the detection of AR (egg count reduction test
      and in vitro egg hatch test) the available figures underestimate the prevalence
      of AR. Finally, possible control measures are discussed in order to avoid or to
      delay the development of resistance.

PMID- 8571669
TI  - [Immune modulation by vitamin D analogs in the prevention of autoimmune
      diseases].
AB  - Vitamin D has been discovered at the beginning of this century. 7
      Dehydrocholesterol is converted to vitamin D3 in the skin and after several
      hydroxylations it is further converted to the active hormonal form, 1 alpha,25
      (OH)2D3. Vitamin D stimulates the absorption of calcium and phosphate and is an
      essential link in bone resorption and formation and calcium metabolism. 1
      alpha,25-(OH)2D3 acts through a vitamin D receptor. These receptors are not only
      present in clinical target organs (kidney, gut, liver) but can also be found in a
      wide variety of "non-classical" tissues (keratinocytes, cells belonging to the
      immune system). Moreover, numerous cells (keratinocytes, macrophages) can locally
      synthetize or can be induced to synthetize 1 alpha,25-(OH)2D3 and these cells are
      responsive to its action. When these data are combined, a possible paracrine
      function of 1 alpha,25-(OH)2D3 can be suspected. Via this paracrine function 1
      alpha,25-(OH)2D3 can suppress the cellular and humoral immunity. Based on the
      discovery of these effects on immune cells in vitro it became clear that 1
      alpha,25-(OH)2D3 might be an interesting molecule to prevent autoimmune diseases
      and organ transplantation. This has already been shown in several animal models
      (Heymann nephritis, diabetes mellitus, experimental allergic-encephalomyelitis,
      lupus). 1 alpha,25-(OH)2D3 demonstrates however some side-effects
      (hypercalciuria, hypercalcemia, bone resorption) and for this reason 1 alpha,25
      (OH)2D3-analogs are developed with dissociated effects i.e. an activity profile
      that allows a specific action on non-classical tissues without calcemic effects.
      Some chemical modifications of the side chain, A and/or CD-ring results in
      "superanalogs" with 10 to 100-fold more activity on cell differentiation and the
      immune system then 1 alpha,25-(OH)2D3 but with less calcemic activity in vivo.
      These biological effects can be explained by differences in pharmacokinetics (low
      affinity for the plasma vitamin D-binding protein and short extracellular half
      life) and increased intracellular activation and gen transactivation. Preclinical
      research must still be done to select the most potent superanalogs and to find
      the exact protocols for the prevention and treatment of autoimmune diseases and
      rejection of transplanted organs.

PMID- 8571670
TI  - [Identification of the breakpoint-flanking markers on chromosomes 1 and 17 of a
      constitutional translocation T(1;17)(P36;Q12-21) in a patient with
      neuroblastoma].
AB  - Neuroblastoma is a childhood cancer which originates in the embryonic tissue of
      the developing sympathetic neural crest. In 1972, Dr. A. Knudson hypothesised a
      similar 'two-hit mutation' model for the origin of neuroblastoma as for
      retinoblastoma and Wilms tumor. In this model, malignant cell growth is caused by
      mutations of both alleles of a tumor suppressor gene. In hereditary tumors, a
      germinal mutation is present in all cells of the individual, a mutation of the
      remaining allele by a somatic hit causes loss of gene function. Sporadic tumors
      result from two somatic mutations of a tumor suppressor gene involving both
      alleles within the same cell. The occurrence of patients with a constitutional
      chromosomal deletion syndrome in association with tumor facilitated the cloning
      of a retinoblastoma gene and of a Wilms tumor suppressor gene. In neuroblastoma,
      cytogenetic and molecular studies suggest the existence of a neuroblastoma
      (suppressor) gene at chromosome 1, at subband 1p36. A constitutional chromosomal
      deletion syndrome was not known for neuroblastoma. We described a constitutional
      chromosome translocation t(1;17)(p36.31-21; q11.2-12) in a patient with
      neuroblastoma. We hypothesised that this translocation, involving the chromosomal
      band 1p36, predisposed the patient to neuroblastoma development by disturbance of
      a gene located at the translocation breakpoint. Consequently, identification of
      the breakpoint flanking markers can be an important step towards the
      identification and cloning of a neuroblastoma suppressor gene. Radioactive in
      situ hybridization methods were first applied on the patient's fibroblasts. Soon
      it became evident that cells with better growth characteristics were needed and
      that the availability of sufficient patient material was essential. Therefore a
      somatic cell fusion experiment was performed between the patient's fibroblasts
      and a thymidine kinase-deficient Chinese hamster cell line. Somatic cell hybrid
      clones were selected on the presence of the derivative human chromosomes 1 and
      17, and of the normal homologues. With the use of fluorescence in situ
      hybridisation (FISH), the position of chromosome 1 and chromosome 17 markers
      respective to the breakpoints was determined on chromosome metaphases of the
      hybrid cell lines containing the human derivative chromosomes. The
      pronatriodilatine (PND) and the adenovirus 12 modification site (A12M2) were
      identified as distal and proximal 'single copy' flanking markers of the
      chromosome 1 breakpoint, respectively. The chromosomal break occurred in a highly
      repetitive region containing an adenovirus modification site and genes encoding
      transfer RNA and small U1-RNA genes. The breakpoint on chromosome 17 is located
      in a region with as proximal boundary the distal part of the neurofibromatosis 1
      (NF1) gene locus and as distal flanking marker the SCYA7 locus, encoding the
      monocyte chemotactic protein-3. Southern blot analysis showed no rearrangements
      of hybrid DNA using single copy probes for the four flanking markers.
      Identification of the four breakpoint flanking markers on chromosomes 1 and 17
      constitutes a pivotal step for the cloning of the translocation breakpoints and
      for the identification of a presumed neuroblastoma suppressor gene.

PMID- 8571671
TI  - [Molecular and functional diversity of inositol triphosphate-induced Ca(2+)
      release].
AB  - A remarkable duality concerning the role of intracellular Ca2+ ions is observed.
      At one side Ca2+ is a universal secondary messenger, and at the other side a
      prolonged increase of the Ca2+ concentration will lead to pathological
      conditions. This is the reason that Ca2+ signals occur in complex spatio-temporal
      patterns such as waves and oscillations. This behaviour reflects the existence of
      a fundamental heterogeneity at the level of the molecular and functional
      parameters that regulate the Ca2+ fluctuations. The molecular basis of the
      complex Ca2+ signals is the regenerative character of the inositol trisphosphate
      receptor (InsP3R) responsible for the release of Ca2+ from intracellular stores.
      In this work, we describe the qualitative and quantitative analysis of the
      expression of the InsP3R isoforms in various cell types. It appeared that there
      exist at least 5 different isoforms and that the isoforms of type II, IV and the
      newly described receptor of type V form a sub-family. The type I receptors are
      ubiquitous, but most cell types express in addition one or more isoforms. In the
      second part of this work, we describe the functional heterogeneity that results
      from the interaction of the InsP3R with InsP3 as well as with allosteric factors.
      In this study we demonstrate that the InsP3R isoforms show remarkable differences
      with respect to their sensitivity for InsP3. An extremely important modulator of
      the InsP3R is the Ca2+ ion itself. Cytosolic Ca2+ has a stimulatory as well as an
      inhibitory role. The Ca2+ present in the lumen of the store is also an important
      regulator of the InsP3R. In the third part of this work we have made a
      correlation between the observed molecular and functional heterogeneity and the
      fundamental physiological properties of complex Ca2+ signals, like quantal
      release, Ca2+ oscillations and Ca2+ waves. Both the isoform diversity and the
      regulation of the InsP3R by cytosolic and luminal Ca2+ are necessary for the fine
      tuning of the Ca2+ signals. The isoform diversity may also play a role in the
      origin of asymmetrical signals present in polarised cells and in the InsP3
      dependent signals through the plasma membrane and through the perinuclear
      membrane.

PMID- 8571672
TI  - Positively promoting health in Papua New Guinea.

PMID- 8571673
TI  - Assessment of long-term glycaemic control in diabetic patients attending Port
      Moresby General Hospital.
AB  - Good glycaemic control is important in preventing the acute and long-term
      complications of diabetes mellitus. We assessed long-term glycaemic control using
      glycosylated haemoglobins in 83 diabetic patients, of mean age 47 years and of
      mean known duration 4.5 years, attending Port Moresby General Hospital over a one
      year period. Significant improvement in glycaemic control was observed in only 11
      (13%) of the patients. Glycaemic control worsened in 13 (16%) and no change was
      observed in the remainder (71%). Mean glycosylated haemoglobin and fasting plasma
      glucose levels were similar at the beginning and end of the study period. Over a
      one-year period 53 patients (64%) exhibited poor control with mean glycosylated
      haemoglobin levels exceeding 10%. Among the 19 newly diagnosed diabetic patients
      (23% of the total) glycaemic control improved in only 2 (11%). Glycaemic control
      was not influenced by sex, treatment, obesity or duration of diabetes. The
      demonstration of poor metabolic control in the majority of patients suggests that
      urgent measures are needed to reevaluate the management of diabetic patients,
      particularly with respect to education and diet. This may improve the poor
      survival rates reported in diabetic patients from Papua New Guinea.

PMID- 8571674
TI  - Typhoid review, Enga Province, from 1986 to 1991.
AB  - A typhoid epidemic in Enga Province between early 1986 and mid-1991 is reviewed.
      Initially 849 cases (46.9/10000 population) were diagnosed clinically in 1986, to
      2.7% in 1990, which can probably be explained by earlier diagnosis and over
      diagnosing of cases as the epidemic progressed. The key factor in the
      transmission seems to have been a low level of personal hygiene with an increased
      transmission risk during public gatherings. Recommendations for the strengthening
      of the control program are made, based on improved diagnosis and patient
      management, health education about personal hygiene and the provision of public
      sanitary facilities.

PMID- 8571675
TI  - Investigation of an outbreak of typhoid fever in two settlements near Port
      Moresby.
AB  - From November 1985 to February 1986 two unplanned settlements near Port Moresby
      experienced a small person-to-person outbreak of typhoid fever, which included
      one death. Investigation showed that of the 20 individuals who were diagnosed as
      either ill, culture positive or a carrier, 15 were related by blood, marriage or
      through shared living quarters. The remaining 5 lived in the same house, but were
      not related to the larger group. Drinking water was contaminated with coliforms,
      but was not implicated. The outbreak resolved with no additional cases after
      February 1986. Outbreaks of this nature highlight the need for continuing public
      health education for local health officers in contact tracing, field testing and
      transportation of specimens, and epidemiological skills in ivestigating person-to
      person outbreaks. They also make a strong case for public health laboratories
      equipped to perform rapid, comprehensive pathological examination of specimens
      collected during any outbreak of infectious illness.

PMID- 8571676
TI  - Hearing loss in Papua New Guinea: a study of outpatients attending Port Moresby
      General Hospital.
AB  - Hearing loss, with its cause, type and degree, was studied in patients who
      attended the Ear, Nose and Throat (ENT) Outpatient Clinic at the Port Moresby
      General Hospital for a period of 5 years from 1987 to 1992. It was found that
      1150 (18%) of the patient population attending the ENT Clinic had hearing loss.
      Audiological evaluation was performed in 583 patients. More males presented to
      the clinic with hearing loss than females. Otitis media was the most common
      identified cause of hearing loss followed by ear trauma and meningitis/cerebral
      malaria. Assaults were the major cause of traumatic hearing loss. Lack of
      awareness on the part of both professionals and parents affected early
      identification of hearing loss, especially in children, whose development of
      speech and language was seriously impaired. The need for implementation of
      suitable rehabilitation measures by the health services is emphasized.

PMID- 8571677
TI  - Unexplained pulmonary hypertension in children in the highlands of Papua New
      Guinea.
AB  - We report the clinical features, electrocardiographic and chest X-ray findings,
      and Doppler-measured pulmonary artery pressures in 22 children admitted to Goroka
      Base Hospital with primary pulmonary hypertension and compare them with findings
      in 10 controls. Symptoms frequently reported by patients were recurrent cough
      (95%) and shortness of breath (77%). 82% of the patients had increased intensity
      of the pulmonary component of the second heart sound. 45% of the patients had
      clinical evidence of right heart failure. Chest X-rays were readable in 14
      patients: the mean cardio-thoracic ratio was 65% and in the controls 58%; the
      mean diameter of the descending branch of the right pulmonary artery was 9 mm and
      in the controls 6.4 mm. 13 patients and 8 controls had electrocardiograms: 11
      patients had right axis deviation, 2 a normal axis, and all showed evidence of
      right ventricular hypertrophy; 7 controls had a normal axis, 1 had right axis
      deviation, and 3 controls had right ventricular hypertrophy. Pulmonary artery
      pressures in the patients ranged from 41 to 137 mmHg with a mean of 79 mmHg. The
      control group had a mean pulmonary artery pressure of 28 mmHg, but 5 of the 10
      controls had pulmonary artery pressures greater than the accepted norm (peak
      systolic pressure less than 30 mmHg). Altitude and chest infection may be playing
      a role in the pathogenesis of pulmonary hypertension in patients in the highlands
      but further studies need to be done to define the causes and the pathological
      changes in the pulmonary vasculature, as well as to determine local norms and the
      natural history of pulmonary hypertension in highland children.

PMID- 8571678
TI  - The use of the polymerase chain reaction for more sensitive detection of
      Plasmodium falciparum.
AB  - The prevalence of Plasmodium falciparum in children and adults living in a
      malaria-endemic area in Papua New Guinea was determined by microscopy and by
      polymerase chain reaction (PCR). The sensitivity of detecting P. falciparum
      infections increased two-fold with PCR. Undetected infections by microscopy were
      more frequent in adults (including adolescents) than in children. Detecting this
      subpatent parasitaemia by PCR resulted in an equal P. falciparum prevalence in
      children and adults; in children the parasitaemia rate increased from 32% to 48%
      and in adults from 23% to 47%. In more than 50% of all blood samples positive for
      P. vivax and P. malariae an underlying P. falciparum infection remained
      undetected by microscopy. The introduction of PCR has opened up new possibilities
      in malaria diagnosis and research.

PMID- 8571679
TI  - Post-traumatic false aneurysm--a frequently missed condition in penetrating
      injuries.

PMID- 8571680
TI  - Liver disease in Papua New Guinea 1981 to 1988, twenty years after the first
      surveys were done.
AB  - Twenty years after the first surveys of liver disease were done cirrhosis and
      hepatocellular carcinoma were still found to be the most important liver diseases
      in Papua New Guinea. Hepatitis B virus appears to be the main cause of both these
      conditions. Data from a number of different sources suggest a prevalence of
      hepatitis B positivity of about 17%. The most significant new finding was grade 3
      iron deposition in 8 patients. This raises the question as to whether iron
      storage disease may now contribute to the spectrum of liver disease in Papua New
      Guinea. Many biopsies in the 1960s and 1980s were interpreted as nonspecific
      hepatitis; in the light of recent observations, at least some of these may have
      been due to hepatitis C infection.

PMID- 8571681
TI  - A therapeutic approach to hypertension.

PMID- 8571682
TI  - [Child psychiatry and genetics].

PMID- 8571683
TI  - [To what extent do school and class-specific factors contribute to aggression in
      schools?].
AB  - In a representative study conducted in Vienna and Lower Austria, 14-year-old
      students from one class each in 79 different schools (N = 1594) answered a
      questionnaire about their experiences at school, the main focus being on
      aggressive acts that occurred at school. In a parallel investigation, the
      students' teachers (N = 554) completed a similar questionnaire. The reports on
      the frequency of aggressive behavior differed widely among the classes. A
      comparison of classes with different levels of aggressive behavior showed that
      solidarity within the classroom and the relationship between teachers and
      students were closely associated with the frequency of aggressive behavior. In
      classrooms with frequent aggressive acts there was a negative attitude towards
      outsiders and the students were less inclined to intervene in an unfair fight.
      Furthermore, they were more critical of discussions with their teachers. Even
      after social and familial factors were controlled for, the influence of school
      specific factors on the frequency of aggressive behavior at school was quite
      large, explaining about 25% of the variance. The consequences for counseling of
      schools and for teacher education are discussed.

PMID- 8571684
TI  - [Evaluation and analysis of social relationships of children in clinical practice
      and research: "Social Relationship Scale for Children"].
AB  - The Social Relationship Procedure for Children (Soziales Beziehungsverfahren f?ur
      Kinder, SOBEKI), a technique employing figure tasks and interviewing, is a new
      clinical psychology assessment instrument for use with children. With this
      instrument it is possible to (a) determine the significant others (social
      network) of 6- to 12-year-old children, (b) measure how specific functions are
      divided among members of a child's social networks, and (c) visualizing cohesion
      and hierarchical structures of the children's networks within and outside their
      families. In the present paper the theoretical foundations, administration and
      assessment of the procedure are outlined. In addition, the results of a
      comparison of children with psychiatric disorders and a healthy control group are
      presented.

PMID- 8571685
TI  - [Psychological aspects of Prader-Willi syndrome. Results of a parent survey].
AB  - Forty-six parents of children and adolescents with Prader-Willi syndrome reported
      on the social and emotional behavior of their children and on parenting stress.
      Standardized questionnaires were used, e.g. a German behavioral questionnaire for
      preschool children and the Child Behavior Checklist. The results showed a high
      frequency of problem behaviors, including stubbornness, temper tantrums,
      obsessions and underactivity. In comparison to age norms, 40% of the preschool
      children were socially immature and 20% had social adaptation problems. Among the
      school-age children 70% had social adaptation problems. More than 70% of the
      mothers reported a high level of parenting stress and are in need of
      psychological counseling.

PMID- 8571686
TI  - [Effects of the new guardianship law for adults on treatment of adolescents on
      the threshold of adulthood].

PMID- 8571687
TI  - [The role of gestagens in prevention and therapy of endometrial hyperplasia].

PMID- 8571689
TI  - [Gestagens and corpus luteum insufficiency].

PMID- 8571688
TI  - [Gestagens and breast diseases].

PMID- 8571690
TI  - [Gestagens and hormone substitution].

PMID- 8571691
TI  - [Hormone therapy of endometriosis--principles and clinical aspects of gestagen
      treatment].

PMID- 8571692
TI  - [Clinical aspects and conservative therapy of Parkinson disease].
AB  - Parkinson's disease is essentially motor. The core symptoms comprise akinesia,
      rigidity and tremor. Concomitantly, signs of autonomic, cognitive and affective
      disturbances may be found. The disease progresses slowly and, without treatment,
      ultimately results in disability and loss of independence. The symptoms can be
      controlled for a long time by pharmacotherapy. Dopaminergic drugs such as L-DOPA,
      dopaminreceptor agonists, and MAO-B- and COMT-blockers can essentially improve
      most of the symptoms. The tremor may be alleviated by central anticholinergic
      drugs. With time, however, unwanted side effects such as "end of dose akinesia",
      "on-off phenomena", hyperkinesis and exogenous psychosis come into play.
      Therefore, pharmacological treatment becomes very complex in the late stages of
      the disease and the unwanted side effects can no longer be sufficiently
      controlled. It is not clear whether conservative approaches will be ever able to
      cope with these problems. This explains the search for novel treatment
      strategies, e.g. neurotransplantation, stereotaxic lesion of the subthalamic
      nucleus or stimulation techniques.

PMID- 8571693
TI  - [Neurotransplantation in Parkinson disease: experimental and clinical results of
      functional reconstruction of the dopaminergic system].
AB  - The first results on functional effects induced by embryonic nigral grafts in the
      rat model of Parkinson's disease (PD) were reported in the late 70 s. It took
      another 10 years before the first publications on PD patients demonstrated
      clinical and neuroradiological signs of improvement after the transplantation of
      allogeneic embryonic nigral grafts. Technical details as well as clinical results
      varied considerably in the first clinical studies. In the last years crucial
      questions have been identified, also because of increasing international
      cooperation, which represent a challenge jointly to basic and clinical
      scientists. The clarification of those questions related to scientific and
      ethical issues will determine which impact the transplantation of embryonic
      nigral dopamine neurons will have as a potential therapy for PD in clinical
      medicine.

PMID- 8571694
TI  - [Neuronal transplantation in animal models of Parkinson disease: in vivo
      voltammetry, tissue cryopreservation and immunology].
AB  - Neuronal transplantation of dopaminergic embryonic ventral mesencephalic cells
      aims at replacing the lost striatal dopamine in Parkinson's disease. Functional
      effects of intrastriatal ventral mesencephalic transplants are reflected in
      improvements of bradykinesia and rigidity. However, a more widespread clinical
      application critically depends on further technical refinements, specifically in
      the area of improved survival of the grafted ventral mesencephalic dopamine
      neurones. This review highlights some of the progress made in the field of
      ventral mesencephalic transplantation in animal models of Parkinson's disease and
      also discusses issues and results obtained by our own research group in Munich.
      Thus we studied whether cryo- or neuroprotective additives during
      cryopreservation of ventral mesencephalic tissue can improve survival of such
      tissue/cells following transplantation. Concerning immunological aspects we
      studied the effects of pooled or co-transplanted embryonic tissue on survival and
      function of grafts and whether immunosuppression with cyclosporine A has
      beneficial effects. Possible neurotoxic effects of cyclosporine A were considered
      in a separate study. Finally, we established in vivo voltammetry to measure
      dopamine release from the graft and effects of the grafts on related parts of the
      dopaminergic system in the living animal. In the clinic we employed guidelines
      for preoperative patient evaluation and respective tests are described.

PMID- 8571695
TI  - [Psychological aspects of neurotransplantation].
AB  - The psychological situation of Parkinson patients and the functions and roles of
      others involved--doctors, donors, caregivers--are discussed with reference to
      ethically based decisions about neurotransplantation. Psychological stressors and
      changes of psychological functions in Parkinson's disease are described. Possible
      psychological risks due to short and long term changes, especially changes in
      emotionality, are discussed. Proposals are made for pre- and post-transplantation
      care involving broad neuropsychological follow up testing and psychological
      counseling, particularly to deal with unfulfilled expectations.

PMID- 8571696
TI  - [Open questions in neurotransplantation. Attempted at an unbiased ethical
      analysis].
AB  - Neurotransplantation utilizing fetal (embryonic) tissue for treating Morbus
      Parkinson is a matter of ethical debate, among professionals as well as the
      public at large. Here, we take a systematic approach to the questions raised to
      facilitate an unbiased ethical analysis and to attempt adequate answers. Possible
      functions of ethics in medicine, principles of ethical reflexion in medicine and
      perspectives of ethical reflexion are differentiated resp. combined. Relevant
      areas of ethical conflict may thus be identified separating at the same time the
      context of explantation from that of implantation. Taking as our starting point a
      systematic discussion of the various open questions, we put forward 5
      conclusions. These should help clarify under which conditions the therapy model
      of neurotransplantation will be admissible.

PMID- 8571697
TI  - [Identity of the personality and personal identity: philosophical questions in
      relation to transplantation of brain tissue].
AB  - Advanced medical technology, though primarily a problem-solver, is also a problem
      generator. Its progress confronts us with ever new problems of decision and with
      the problem of giving these decisions a sound ethical backing. The challenge for
      philosophy is, in this situation, to act as a kind of go-between: It should make
      a serious attempt to mediate between innovative medical technology and popular
      scepticism, and it should provide intellectual guidance for a structured and
      rational debate. Brain tissue transplantation is confronted mainly with two
      ethical problems: 1. Under which conditions are we justified to take
      transplantable brain tissue from aborted human embryos or fetuses? 2. Is it
      acceptable that the implantation of brain tissue taken from a human embryo or
      fetus might disturb, in one way or other, the identity of the recipient? To
      answer these questions, difficult anthropological issues must be discussed: 1.
      What are the criteria of death applying to embryos and fetuses? 2. What are the
      conditions for saying that the identity of a person is changed? The present
      contribution makes an effort to clarify the latter question. It examines the
      concept of identity in the context of brain tissue transplantation, makes a
      distinction between identity of personality and personal identity, and argues
      that even major changes of personality resulting from brain tissue
      transplantation would not by themselves amount to a change in personal identity.
      This result has to be reconsidered, however, in the light of the fact that brain
      tissue transplantation alters the make-up of the recipient's brain.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8571698
TI  - [Importance of the brain in body-soul discussion from the history of medicine
      perspective].
AB  - Since the earliest time medicine has considered our intellectual-psychic
      abilities in relationship to organs and substrata. Originally blood and its
      presumptive production resp. depot organs liver and heart acted as soul carriers.
      Gradually the brain obtained superiority in the body-soul-discussion and during
      the course of development nearly any structure of the brain was taken into
      consideration as seat of the soul and the sensorium commune. In the meantime the
      unity of body and soul never has been controversial among the former medical
      authors. Since the central nervous system took place of the blood vascular system
      already at an early time it follows that the brain equally in past and present
      passed for the material form of our intellectual-psychic abilities. It is true,
      today we renounce to speak in the body-soul-discussion of single structures of
      the brain--this has been done intensively and extensively for us by the searchers
      in former times--, but we still follow the old localisation concept perceiving in
      the brain and its estimated hundred milliards of nerve cells the unimaginable
      complex organ that offers the substratum for our intellectual-psychic abilities.
      Much is not yet realized. But: The genetic material was up to the present a
      "black box". Today light is fallen in. The efforts concerning this light
      incidence into the "black box" of the brain must be continued in favour of a
      successful restorative neurotransplantation.

PMID- 8571699
TI  - [Computer-oracle-brain].
AB  - The main question of this essay is this: What can the hypotheses of Artificial
      Intelligence (AI) that brains work like computers contribute to the question
      whether neurotransplantations are permissible or not. My attitude is primarily
      critical. I point out that the believe that we could exchange parts of the brain
      like parts of a computer is erroneous. Many mathematical functions are not
      absolute but only relative computable. The computation of the latter is only
      possible by using an oracle (a stock of knowledge), which has to be implemented
      in the computer respectively in the brain. Hence, one should know in advance,
      before a transplantation is performed, in which part of the brain the oracle is
      located. Otherwise we would not know whether the oracle will be damaged by a
      neurotransplantation, and, hence, whether the persons ability to think will be
      changed. Of course, this is only a presupposition, not the solution of the
      ethical question of the legitimacy of neurotransplantations.

PMID- 8571700
TI  - [The emotional self with reference to neurotransplantation].
AB  - From a systems-theoretical point of view the concept of the "self" is represented
      and discussed in relation to phenomena of emotion. The question is raised as to
      whether structural changes of the brain induce changes of the "emotional self"
      and thereby induce changes of personal identity. The philosophical and
      neurobiological implications of these considerations are discussed in relation to
      transplantation of neuronal cells. The hypothesis is discussed that neuronal
      transplantation has to avoid the transfer of intact neuronal tissue and should be
      restricted to transfer of isolated cells, since otherwise parts of other neuronal
      "selves" might be transmitted.

PMID- 8571701
TI  - [Transplantation of human fetal brain cells: theological-ethical aspects].
AB  - Using fetal brain cells for therapeutic purposes after a spontaneous abortion can
      be justified under similar pre-conditions like the removal of an organ post
      mortem. With an artificially induced abortion, however, there is the danger of
      justifying the act of abortion by combining it with that positive purpose. In
      this case any therapeutic utilization of fetal brain cells would only be
      justifiable, if every step of such a procedure could completely be isolated from
      the ethically unjustifiable abortion.

PMID- 8571702
TI  - [Use of embryonal CNS tissue in Parkinson disease from the medical ethics
      viewpoint].
AB  - The transplant therapy discussed here contains ethical problems of some weight.
      In order to analyse them it is inevitable to distinguish between merely
      indirectly connected ethical problems and those that are central to this therapy.
      To the latter belong dilemmas on the individual as well as the social level,
      problems concerning the model of consent (on part of the pregnant woman) and the
      application of the 'therapeutic indication' (on part of the Parkinson patient).
      CONCLUSION: this transplant therapy is ethically highly questionable and should
      not be generally permitted; limited experiments for research may be necessary and
      ethically tolerable. More urgent is the pursuit of alternative therapeutic
      methods some of which are already being explored.

PMID- 8571703
TI  - [Legal aspects of neurotransplantation].
AB  - The use of human embryonic brain tissue for Transplantation has to be orientated
      in the need of protection for the embryo or fetus. Tissue derived from an
      abortion can only be used when a connection between the abortion and the
      application is excluded. The decision for an abortion should not be influenced by
      a possible usage of the tissue, as is stated in the guidelines of the german
      medical council for the use of fetal cells and tissue as well as in the
      guidelines from NECTAR. Criteria for death include brain death and cardiovascular
      arrest. If brain death can not be ascertained, one has to relay on the
      irreversible absence of spontaneous breathing and heart beat (after the exclusion
      of reversible factors like hypothermia or drugs). Authorization for the use of
      fetal tissue is given by the mother or the parents, their consent is a
      prerequisite for the use of fetal tissue.

PMID- 8571704
TI  - [Epidemic outbreak of dysentery Sonnei in a child care center].

PMID- 8571705
TI  - [Epidemic outbreak of Sonne dysentery in a child care center (epidemiologic
      practice No. 1. Authors' comments and answers to questions)].

PMID- 8571706
TI  - Evidence for thrombin-induced human platelet secretion regulated by the
      cytoskeleton.
AB  - Human blood platelets store an abundance of growth factors, adhensive proteins,
      coagulation factors, platelet-specific proteins, calcium, serotonin, and adenine
      nucleotides in their secretory organelles. After exposure to stimuli (thrombin,
      collagen, ADP, etc.), the platelets undergo a rapid series of morphological
      change from characteristic disks to spheres with several filopodia, adhension to
      the inner surface of blood vessels, and aggregation among the platelets. Most of
      these changes are usually accompanied by secretion or release of dense bodies
      (release I) and alpha-granules (release II). The secreted products play essential
      parts in a variety of important physiological and/or pathological events, such as
      hematosis, thrombosis, blood coagulation, inflammation, and atherosclerosis.
      Little is known, however, for regulatory mechanism of platelet secretion.
      Platelets are a distinct kind of cells with many special organelles, but without
      a nucleus. It also contains a large amount of cytoskeleton. The numerous
      investigators have suggested that the platelet responses to stimuli are
      intimately linked to events involving cytoskeleton within the platelets. During
      platelet activation, as revealed by electron microscopy, the secretory organelles
      become centralized and enveloped by circular microtubules and a filamentous
      network. It is implied a possible relationship between cytoskeleton and platelet
      secretion. However, the precise role of cytoskeleton in platelet secretion
      remains uncertain. By using exposed GMP-140 (a platelet granule-membrane protein
      with MW of 140 kDa) as a specific signal of secretion, the present study was
      designed to investigate the effects of microtubular and microfilamental
      inhibitors on thrombin-induced platelet secretion.

PMID- 8571707
TI  - [An EGFR antisense oligodeoxynucleotides and its phosphorothioate analogue
      inhibit the growth of human hepatocarcinoma BEL-7404 cells].
AB  - We have previously reported that the malignant phenotype of human liver carcinoma
      cell line BEL-7404 was reversed by antisense EGFR RNA. The aim of this paper is
      to explore the effects of an oligomer targeted to mRNA for EGFR and growth of BEL
      7404 cells. A 21-mer oligodeoxynucleotides (ODNs) complementary to the 5'
      initiation region of mRNA for EGFR was synthesized and added to medium. The
      results showed that the growth of BEL-7404 cells was inhibited by ODNs at
      concentration of 3.2 mumol/L. Inhibition of DNA synthesis of BEL-7404 cells was
      dose-dependent and reached to 62.1% at 3.2 mumol/L as measured by 3H-thymidine
      incorporation test. The inhibition of EGFR gene transcription of the cells was up
      to 10.5% and 14.3% respectively after incubation with ODNs by 5 and 24 hours as
      measured by densitometric scanning of dot (RNA) blots of EGFR. The EGFR protein
      (P 170) expression was also found to be blocked by 4 days' antisense oligomer
      treatment up to 37.4% as measured by densitometric scanning of specific band of
      Western blot. The oligonucleotide phosphorothioate (S-ODNs) complementary to the
      same region of the gene was also synthesized and its growth inhibition effects on
      BEL-7404 cells were compared with those of unmodified oligomers. ODNs attained
      their highest effect within 30 hours. The proliferation inhibition rate of the
      cells didn't increase when cells were cultured in serum free medium. In contrast,
      the S-ODNs induced inhibition reached comparable level after 96 hours treatment
      as measured by 3H-thymidine uptake and the effect lasted longer, 1 mumol/L S-ODNs
      showed a little effect on BEL-7404 cells' proliferation. We concluded that the
      antisense oligomers directed to mRNA for EG-FR could inhibit the BEL-7404 cells
      growth by blocking the EGFR gene expression in some degree and the
      phosphorothioate analogues were more stable than the unmodified ODNs in vitro.

PMID- 8571708
TI  - Flow cytometry analysis of the neutralization effect of anti-IL-8 McAbs on IL-8
      activated human granulocytes.
AB  - Two hybridoma clones, I8-S2 and I 8-63, secreting anti- IL-8 antibodies were
      constructed from fusion of immunized spleen cells of BALB/c mice with either Sp
      2/0 or 653 myeloma cells. They recognized different epitopes on IL-8 molecule. IL
      8 could activate human granulocytes and induce the elevation of [Ca2+]i. Through
      flow cytometry analysis the two clones displayed different neutralizing effects
      on the cell activation function of IL-8. The neutralizing effect of clone I8-S2
      was apparently higher than that of clone I8-63. It is suggested that the cell
      activation function of IL-8 is restricted to a certain epitope of IL-8 molecule.

PMID- 8571709
TI  - [The distribution of tumor suppressor gene APC mRNA in guinea pig brain].
AB  - The APC gene was identified in 1991 at chromosome 5 q 21, which is responsible
      for the familial adenomatous polyposis (FAP). The gene has been classified as one
      of the tumor suppressor genes. The APC gene mutations were suggested to initiate
      sporadic as well as inherited colorectal neoplasia and to be related to mental
      retardation. The different forms of APC gene expression and their association to
      carcinogenesis have been carefully studied. However, the function of APC gene in
      the central nervous system has not been known. In this study, on the basis of the
      cDNA cloning of APC homologue in the guinea pig by Dr. Fan Meng, we rescued this
      fragment including the full length encoding region from plasmid pMe 18s and then
      subcloned it into the polylink site of the plasmid pBluscript KS. Both
      digoxigenin labeled sense and anti-sense RNA were synthesized by in vitro
      transcription. RNase protection assay and in situ hybridization enable us to
      examine the distribution of APC transcripts in guinea pig brain. Strong signals
      were detected in hippocampus. APC mRNA was mainly localized in the pyramidal
      neurons of CA 1, CA 3, as well as in the dentate granule cells; the cerebellum
      granular cells also showed strong staining; in the cerebrum, the parietal and
      primary olfactory cortex showed stronger signals than the frontal cortex; in
      olfactory bulb, positive cells with strong signals were observed: the brain stem
      showed a relatively weaker staining. Very similar expression pattern was also
      shown in embryonic guinea pig brain; except that the expression of APC gene in
      frontal cortex and olfactory bulb was stronger than that in adult animals. The
      results suggest that the APC transcripts in brain may play an important role
      during the early development of the central nervous system. Further study may
      enable us to take a deeper insight into the mechanism underlying inherited mental
      deficiency.

PMID- 8571710
TI  - [Cloning and overexpression of rat ovary LH/hCG receptor cDNA in insect cells].
AB  - Luteinizing hormone/human chorionic gonadotropin receptor (LH/hCG receptor) is a
      glycosylated protein coupled with G-protein. This paper reports screening of
      LH/hCG receptor cDNA from rat ovary cDNA library and the overexpression of the
      cDNA in insect cells. Full length of LH/hCG receptor cDNA is 2403 bp encoding
      signal peptide and matured protein of LH/hCG receptor. The cDNA is overexpressed
      in insect cells using baculovirus expression vector pVL 1393. The apparent
      molecular weight of purified receptor using immunoaffinity chromatography is 120
      Kd and 92 Kd under non-reducing and reducing conditions, respectively. Ligand
      binding assay and Scatchard Plot analysis indicates that Kd is 8.4 x 10(-9) mol/L
      which is similar to that of the purified receptor from CHO cells.

PMID- 8571711
TI  - [Relationship between CENP-B gene expression and the cell cycle].
AB  - The centromere/kinetochore is a specialized structure at the primary constriction
      of mammalian chromosomes. It participates in and is necessary for the mitotic
      chromosome movement. Centromere Protein B(CENP-B) is a highly conserved protein
      located at the centromere/kinetochore region. In this article, we explore the
      relationship between CENP-B expression and cell proliferation. HeLa cells were
      synchronized at different phases of the cell cycle and the synchronized cells
      were examined by flow cytometry and 3H-TdR labelling. ACA immunostaining showed
      the discrete single spots in nuclei of the cells at G1 and S phase, and spots in
      pairs mostly in those at G2 phase. Dot blot and Northern blot indicated that CENP
      B gene was expressed at all phases of the cell cycle, but the expression level
      very much different with the highest at G2 phase and the lowest at S phase.
      Interestingly relatively high expression of CENP-B gene was also found in M
      phase, showing the continuity of the CENP-B gene expression during the cell
      cycle. This continuity implies a possibility that the assembly of the new
      centromere/kinetochore can not occur until centromere proteins reach a critical
      concentration when cells enter S phase and G 2 phase. Also, the continuous
      expression of centromere proteins may be necessary for the centromere/kinetochore
      function. In addition, the relationship between CENP-B gene expression and the
      nuclear skeleton was investigated. The nuclear skeleton-associated DNA extracted
      after Bam HI digestion were hybridized with 32P-labelled cDNA of CENP-B gene by
      means of Southern blot technique. The results that there stronger positive
      hybridization reaction in G 2 phase than in S phase indicated that CENP-B gene
      was more closely associated with the nuclear skeleton in G 2 phase cells than in
      S phase cells, which was in consistence with the level of the CENP-B gene
      expression at G 2 and S phase cells.

PMID- 8571712
TI  - [Intercellular relationship of notochord determination of Xenopus laevis].
AB  - During the process of determination, the presumptive notochord is situated
      beneath neuroepithelium, flanked at two sides by presumptive somites and
      underlain with archenteron roof ventrally. Among these neighbouring embryonic
      tissues, presumptive somites were found to exert the main influence on notochord
      determination. By electron microscopic observations, the presumptive notochord
      and somite cells were seen to situate either close to each other (plate I, Fig.
      1) or connected by cytoplasmic processes forming intercellular lumen (plate I,
      Fig. 5). Coated pits and coated vesicles appeared at the outer surface of both
      types of cells (plate I, Figs. 1-4). For the presumptive somite cells, spherical
      bodies of different sizes and variable contents were observed either near or
      protruding from the outer surface (plate II, Figs. 6-10). The spherical bodies
      were also found in the intercellular lumen (plate III, Fig. 11). These spherical
      bodies were mainly composed of granules, loosely scattered or densely packed. The
      granules were of similar size and similar shade of electron staining as those of
      ribosomes of the presumptive somite cells. For the presumptive notochord cells,
      no spherical bodies of the above mentioned type were found, but phenomenon of
      engulfing luminal material was observed (plate III, Fig. 12). The significance of
      the appearance of these spherical bodies in the determination of notochord cells
      has been discussed.

PMID- 8571713
TI  - Complications after elective gastric resection for duodenal ulcer. Multivariate
      analysis of risk factors.
AB  - The records of 545 consecutive patients, who underwent elective Billroth II
      gastric resection for pyloric or duodenal ulcer were examined retrospectively to
      identify a group of high-risk patients for life threatening postoperative
      complications or death. Thirty-two preoperative clinical, endoscopic, surgical
      and haematological variables were analyzed by stepwise logistic regression. Major
      complications occurred in 39 patients (7%) and eight patients (1.5%) died. The
      patient characteristics associated with the major complications and death were
      liver cirrhosis (Odds ratio 6.7 95% Confidence interval 1.3-33.8), white blood
      cell count > 10,000/mm3 (Odds ratio 5.5 95% Confidence interval 1.7-17.3),
      previous abdominal surgery (Odds ratio 4.6 95% Confidence interval 1.7-12.1), and
      ulcer penetrating contiguous structures (Odds ratio 3.3 95% Confidence interval
      1.2-8.9). There was no statistically significant interaction between the above
      risk factors in causing complications or death. It can be concluded that even if
      only one of these four risk factors is present in patients undergoing elective
      surgery for duodenal ulcer a riskless technique, such as proximal gastric
      vagotomy, should be used instead of Billroth II gastric resection.

PMID- 8571714
TI  - Ruptured subcapsular hepatic haematoma secondary to "HELLP syndrome".
AB  - We report the history of a pregnant woman who suffered from a ruptured hepatic
      subcapsular haematoma, responsible for a major haemoperitoneum. This rare event,
      final evolution of the "HELLP Syndrome" led us to review pathophysiology and
      treatment of the syndrome.

PMID- 8571715
TI  - Prospective analysis of 192 consecutive cholecystectomies: a comparative study
      between laparoscopy and laparotomy.
AB  - The hospital records of all the patients who underwent cholecystectomy because of
      specific biliary symptoms, between October 1990 and March 1993, were
      prospectively analyzed. The series consisted of 192 patients (159 women and 33
      men), the mean age was 56 years and the mean body mass index was 26. Indication
      for surgery was uncomplicated gallstones in 113, common bile duct stones in 28
      and cholecystitis in 51 patients. In those groups, respectively 94 (83%), 16
      (57%) and 23 (45%) patients had a laparoscopic cholecystectomy. In total,
      laparoscopic cholecystectomy was successfully performed in 127 (95%) of the 133
      patients in whom it was attempted. When compared with laparotomy, laparoscopic
      cholecystectomy was associated with shorter operative time: 88 +/- 41 min. (Mean
      +/- SD) versus 132 +/- 64 min. (p < 0,001), shorter postoperative hospital stay:
      5 +/- 3 days versus 13 +/- 7 days (p < 0.001) and reduced cost of
      hospitalization: 103.301 +/- 51.062 BF versus 186.931 +/- 113.651 BF (p < 0.001).
      We noted an equivalent perioperative morbidity incidence in the two groups. The
      advantages of laparoscopy compared to laparotomy were recorded whatever the
      indication for cholecystectomy was. Therefore, with the increasing experience of
      surgeons and the improving quality of laparoscopic instruments, we think that
      laparoscopy can be considered for all patients requiring cholecystectomy.

PMID- 8571716
TI  - Small bowel diverticulosis. A forgotten diagnosis.
AB  - Small bowel diverticulosis (SBD) have the lowest incidence of diverticulosis of
      the alimentary tract. The incidence differs from 0.09% to 2.3% depending on the
      reporting physician. SBD are pseudodiverticula, consisting of mucosa only. The
      causes of SBD are not clear, but the "locus minoris resistentiae" theory is most
      widely accepted. Overactive or irregular peristalsis bulges the mucosa out
      through vascular defects in the bowel wall. Only meticulous radiographic
      techniques can lead to a diagnosis. Preoperative diagnosis is exceptional. SBD
      can produce chronic abdominal discomfort. Acute complications are also numerously
      described, giving rise to a surgical emergency. Resection of the involved segment
      is then the only good procedure. Two cases presenting major complications are
      discussed, followed by a review of the literature.

PMID- 8571717
TI  - Use of an absorbable polyglactin mesh for the prevention of incisional hernias.
AB  - Nowadays, incisional hernias are still one of the more common complications of
      abdominal surgical procedures. A population, at high risk of developing an
      incisional hernia, has been chosen for this study, namely patients suffering from
      morbid obesity. The aim of the study was to compare prospectively the incidence
      of incisional hernias in 2 groups of patients operated upon for morbid obesity
      (Vertical Silicone Ring Gastroplasty) with or without intraperitoneal polyglactin
      mesh. Patients were randomly assigned in the 2 groups. For this preliminary
      study, 112 patients operated upon before 01/04/1992 were selected; the mean
      follow-up period was 28.3 months (S.D.:5.7); 81 patients have been reviewed
      personally, 31 interviewed by phone call or mail. The 2 groups of patients were
      not significantly different as regarding age, sex, weight, body mass index,
      diabetes and wound infection. Sixteen incisional hernias were observed in the
      group with mesh and 17 in the group without mesh. According to these preliminary
      results, there is no argument for recommending the use of the polyglactin mesh in
      the prevention of postoperative incisional hernias, in obese patients.

PMID- 8571718
TI  - Sciatic hernia.
AB  - The case of a young female patient with advanced gastric carcinoma and right
      sided sciatic hernia is reported. Palliative gastrectomy was considered the only
      option. The reducibility of the hernia was confirmed at laparotomy but the
      herniorraphy was performed using the gluteal approach. Based on their previous
      experience with this entity, the authors compare the advantages and drawbacks of
      the approaches and methods for repair of sciatic hernias.

PMID- 8571719
TI  - Surgical technique for reinforcement cardiomyoplasty.
AB  - The current technique for reinforcement cardiomyoplasty in man is detailed. The
      authors emphasize the critical points that determine the perfect execution of
      this operation. This innovative surgical approach to heart failure is
      continuously evolving and, therefore, may be subject to improvement. The major
      principles however remain valuable.

PMID- 8571720
TI  - Is the use of ankle saphenous vein for carotid artery patch closure justified?
AB  - Saphenous vein patch angioplasty has been introduced to prevent early and late
      restenosis after carotid artery endarterectomy. We describe a case of vein patch
      rupture on the first postoperative day, resulting in death of a hypertensive
      female patient. Although the incidence of this complication is low (0.5 to 1%),
      the morbidity and mortality rate is dramatically high when it occurs. In similar
      cases published, saphenous vein harvested from the ankle is involved almost
      exclusively, suggesting that small-diameter veins have a higher risk of rupture
      when used as a carotid patch. Old age, female gender, diabetes and arterial
      hypertension seem to be further factors negatively influencing the physical
      properties of the vein. Therefore, if a venous patch is needed in selected
      patients most probably in female patients with small internal carotid arteries,
      it seems appropriate to use the proximal part of the saphenous vein from the
      groin or the thigh.

PMID- 8571721
TI  - Pulmonary metastasectomy.
AB  - Between 1988 and 1994, 24 patients underwent 32 procedures for pulmonary
      metastases. Primary tumours were gastrointestinal, malignant melanoma, osteogenic
      sarcoma, renal cell carcinoma, head and neck cancer and finally testicular
      carcinoma. Age ranged from 16 to 78 years, with a female/male ratio of 7/17.
      Pulmonary metastasectomy was performed in 9 cases through median sternotomy, in
      21 cases through thoracotomy and in 2 cases by thoracoscopy. In 9 cases repeated
      resection was necessary. Overall mortality was 0% (95% confidence limits are 0.00
      +/- 14.25). Computed tomography of the chest in combination with tumour markers,
      were most important during follow-up to detect recurrent disease. The overall 5
      year actuarial survival and disease-free survival were 0.56 +/- 0.17 and 0.30 +/-
      0.14 respectively. With regard to testicular carcinoma 5-year actuarial survival
      was 100%. Pulmonary metastasectomy is a recommended procedure in the treatment of
      selected patients with metastatic pulmonary disease. Resections should be as
      conservative as possible and if necessary, repeated. In our study this procedure
      proved especially effective in case of testicular carcinoma.

PMID- 8571722
TI  - Hernia of the diaphragm: a clinical case and review of the literature.
AB  - Diaphragmatic rupture occurs in 25% of the thoracic and abdominal blunt injuries.
      It may be discovered immediately or sometimes several months or even years after
      the trauma. The diagnosis can be made easily on the basis of a standard chest X
      ray. Barium swallow examination, computerized tomography Scan and especially
      Magnetic resonance imaging can be helpful for differential diagnosis. Surgical
      treatment is always necessary.

PMID- 8571723
TI  - Primary arthrodesis of the injured knee: still a solution in 1995? A case report.
AB  - After major trauma of the knee joint, conservation and reconstruction of the
      different bony, ligamentary and soft tissue structures is usually attempted. The
      end results of these reconstructive procedures are not always gratifying, and in
      many cases significant instability remains, combined with severe restriction in
      motion, pain or infectious problems, leading to severe functional impairment.
      Many patients need secondary corrective procedures, such as arthrodesis. We
      present a case of an unusual injury to the knee with massive destruction, loss,
      and contamination of bony, ligamentary, and soft tissue structures. Because
      attempts at reconstruction would have led to the above-mentioned problems,
      including possible life-threatening septic complications necessitating
      amputation, a primary arthrodesis was performed, followed by simple
      reconstruction of the soft tissue envelope. Two years after the accident, the
      patient is doing very well. To our knowledge, no such cases have previously been
      described. We therefore want to communicate our experience with this procedure,
      which led to an early, pain free, and good functional recovery.

PMID- 8571724
TI  - Peculiar indications for the pedicled or free rectus abdominis flap in
      reconstructive surgery. A review of our experience.
AB  - Among all known flaps, the rectus abdominis muscle flap possesses an unique
      diversity in flap designs due to the special vascular supply of the abdominal
      wall. The axial vascularization of the rectus abdominis muscle gives ofF several
      musculocutaneous perforators, which are mainly located in the periumbilical
      region. Abdominal wall skin perfusion is guaranteed by spoke-wheel like vessels
      arising from these perforators. Subsequently several designs (muscle,
      myocutaneous and myosubcutaneous) are possible, by varying the included tissue
      and the position of the skin island. We described 7 cases where the rectus
      abdominis muscle was used as a muscle or myocutaneous flap for reconstruction of
      large defects. In most cases a pedicled transfer was necessary, possible and
      sufficient to reconstruct the difficult defects in various body regions. Great
      amounts of well perfused tissue can be transferred with still possible primary
      closure of the donor site. Due to its rich perfusion and constancy of vascular
      pattern, it represents an excellent and safe pedicled reconstructive procedure
      for large defects of the thorax, the abdomen, the forearm or the hip and pelvis
      where free tissue transfers are impossible or contraindicated. No other local
      transposition would have achieved this goal, due to the lack of volume and
      mobility. Moreover the flap is ideal for reconstruction of contour deficiencies
      due to the abundance of fat, as for example in breast or buttock reconstruction.
      However the flap is not the first choice for traumatic and infected wounds where
      fat tissue is not desired.

PMID- 8571725
TI  - Adenocarcinoma of the ileum. A case report, and review of the literature.
AB  - A 47-year-old female presented with intestinal occlusion and a lower abdominal
      mass. On laparotomy, a 10 cm diameter mass was discovered involving the ileum,
      jejunum, vagina and the bladder. Pathological studies conclusion was a primary
      adenocarcinoma of the ileum involving the jejunum. Small bowel carcinoma is rare.
      It occurs between sixty- and seventy-year-old equally in male and female. It
      presents most frequently in the duodenum, sometimes in the jejunum, and
      occasionally in the ileum. The symptoms are not specific and do not point to the
      diagnosis which must be made radiologically and endoscopically. Currently, for a
      minority of patients, surgical resection remains the only hope of cure.
      Palliative resections and bypass procedures can prevent occlusion or
      subocclusion.

PMID- 8571727
TI  - Tight glycaemic control prevents diabetic complications.

PMID- 8571726
TI  - Diagnosis and treatment of differentiated carcinoma of the thyroid gland.

PMID- 8571728
TI  - [Epidemiological study on neonatal septicemia and meningitis in Belgium].
AB  - Epidemiological data were collected for 219 cases of neonatal septicaemia and/or
      meningitis. In two thirds of the cases the diagnosis was made in newborns aged 4
      days or less. Risk factors related to the delivery, to the health status of the
      infant at birth and to pregnancy were mentioned respectively in 74, 63 and 36% of
      the cases. Half of the newborns given antibiotics in prophylaxis received an
      association of aminopenicillin and aminoside. In more than four fifths of the
      cases the bacterium was only isolated from blood. In newborns aged 4 days or less
      at the time of diagnosis, S. agalactiae was the most frequently isolated agent
      (50%). In newborns aged 5 days or more at the time of diagnosis, E. coli was the
      most frequent isolate (23%), followed by S. agalactiae and coagulase-negative
      Staphylococcus (20%). The lethality was 18%. About three fourths of the children
      dying from the infection, died during the first week of life. For the children
      who did not die during their stay in hospital, the duration of hospitalization
      was longer than 4 weeks in 41%.

PMID- 8571729
TI  - Anti-hepatitis C virus positivity (HCV) in Belgian volunteer blood donors: source
      of contamination and HCV-testing among donors and related recipients.
AB  - We investigated a group of Belgian HCV-100 Elisa positive volunteer blood donors
      for potential sources of contamination and the presence of liver biochemical
      abnormalities. In addition, results of serological testing and liver biochemistry
      of their related blood products recipients were also analysed. In blood donors,
      anti-HCV-100 repeat reactive rate was 0.77% with a 34% rate of abnormal liver
      function tests. A potential source of parenteral exposure was found in all donors
      with RIBA-confirmed HCV-100 positivity. Among recipients, anti-HCV-100 RIBA-2
      positive blood product donations were associated with RIBA-2 seroconversion, a
      history of transfusion in donors being of high predictive value of infectivity.

PMID- 8571730
TI  - Heparin-associated thrombocytopenia: an update.
AB  - The use of heparin may be complicated by two types of thrombocytopenia (HAT):
      type I occurs early, is transient, and has no clinical relevance, while type II
      may lead to very severe manifestations (arterial or venous thromboses and more
      rarely bleedings), that are still underestimated by some clinicians. HAT-type II
      most frequently develops after use of therapeutic doses of unfractionated heparin
      (UH) but has also been described less frequently after use of very low doses of
      UH, of low molecular weight heparins (LMWH), and even of polysulfated
      glycosaminoglycosans devoid of anticoagulant action. The estimation of the
      incidence of HAT-type II and of related thromboses is a very difficult matter.
      Recent observations suggest that thromboses (notably venous) may be more frequent
      than previously estimated. HAT-type II pathophysiology includes the formation of
      immune complexes at the surface of platelets; the antigen has been shown to be
      most often platelet factor 4 bound to heparin while the antibody is recognized by
      platelet Fc gamma RII receptors. Thromboses result most probably from activation
      of both platelets (leading to the formation of microparticles) and endothelial
      cells. Several biological tests are presently available for diagnosing HAT-type
      II but none of them has been shown to be ideal. The prevention of HAT-type II
      requires history taking preference of LMWH to UH, early start of oral
      anticoagulation, and platelet monitoring from the fifth day of heparin therapy.
      The therapy of HAT-type II implies immediate discontinuation of heparin and
      avoidance of platelet transfusions, unless severe bleeding occurs. If further
      antithrombotic treatment is deemed necessary (probably in all cases), several
      options are possible but presently, the most recommended ones are Org 10172 or
      Ancrod; embolectomy or thrombolysis may also be required if a new thrombotic
      event has developed. A very difficult dilemma concerns patients previously
      sensitized to heparin and who present a clinical situation that theoretically
      mandates re-exposure to UH, such as by-pass surgery; prostacyclin analogues may
      be successfully used in such cases. Recent developments in the therapy of HAT
      type II include recombinant hirudin or synthetic analogs, or use of some
      intravenous immunoglobulin preparations. Possible candidates are the heparin
      synthetic pentasaccharide and recombinant tissue factor pathway inhibitor.

PMID- 8571731
TI  - The clinical manifestations of ochronosis: a review.
AB  - Ochronosis is a rare disease caused by an inherited lack of homogentisic acid
      oxidase. Alkaptonuria is the presence of homogentisic acid in urine. Ochronosis
      is characterized by the deposition of a dark pigment in tissues rich in collagen.
      A wide spectrum of clinical manifestations is described. The most important signs
      are ochronotic arthropathy, ocular and cutaneous pigmentation, genitourinary
      tract obstruction by ochronotic calculi and cardiovascular ochronosis, especially
      calcification and stenosis of the aortic valve. The constellation of these
      clinical signs should suggest the diagnosis which is confirmed by the detection
      of homogentisic acid in urine. There is no cure for the disease and treatment is
      based on symptomatic measures.

PMID- 8571732
TI  - Legionnaires' disease and acute renal insufficiency: report of a case and review
      of the literature.
AB  - We report the case of a 73-year-old man, who developed acute renal failure in
      association with a Legionella pneumophila serotype 1 pneumonia. Renal biopsy
      revealed a tubulointerstitial nephritis. Treatment with erythromycin, rifampicin
      and haemodialysis resulted in a clinical resolution of the pulmonary and renal
      syndromes.

PMID- 8571733
TI  - Tumor necrosis factor and lymphotoxin ligand-receptor system in
      lymphoproliferative disorders.

PMID- 8571734
TI  - [Current approaches of treatment for myelodysplastic syndrome (MDS)].
AB  - The number of treatment modalities for patients with myelodysplastic syndromes
      (MDS) has increased, but curative options are still limited. For the majority of
      patients with low risk there is no standard therapy other than appropriate
      supportive care. In selected patients anabolic steroids, differentiation inducers
      such as cis-retinoic acid (RA), interferon alpha or gamma have been claimed to be
      active. Application of growth factors such as granulocyte-macrophage colony
      stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), and
      interleukin 3 (IL-3) improves neutrophil count and diminishes frequency of
      infectious complications, but responses are incomplete and of short duration.
      Preliminary results of erythropoietin (Epo) applied in therapeutical doses are
      disappointing, giving an improvement in 15-20% patients. Epo in large doses
      produces greater and sustained responses, but this treatment is too expensive.
      Low-dose cytosine arabinoside (Ara-C) induces a response rate in 25-30% patients,
      however, no survival advantage has been obtained. Addition of RA or GM-CSF
      produces response rates comparable to Ara-C alone, but also with no prolongation
      in survival. Bone marrow transplantation (BMT) offers a good chance of long-term
      disease-free survival if is performed in an early stage of the disease or in
      complete remission, however, it is limited to patients below 55 years with an HLA
      identical donor. Relatively young, high risk patients not eligible for allogeneic
      BMT should be considered for treatment with intensive polychemotherapy.

PMID- 8571735
TI  - [Progress and controversy in treatment of Hodgkin's disease].
AB  - Hodgkin's disease (HD) is a malignant disease originating from hematopoietic
      tissue which is characterized by the presence of Hodgkin and Reed-Sternberg
      cells. The vast majority of HD patients are cured with current standard therapy.
      Both megavoltage radiotherapy and combination chemotherapy are effective
      treatment modalities. Radiotherapy is curative for localized Hodgkin's disease,
      and it is now generally agreed that advanced Hodgkin's disease can be cured by
      combination chemotherapy. Data from uncontrolled trials suggest that in patients
      with advanced disease the addition of low-dose radiation to sites of previous
      disease involvement is associated with better long term and relapse free
      survival. Patients who relapse after initial treatment with chemotherapy are
      considered suitable candidates for systemic salvage programs. These programs may
      include treatment with the same drugs, the use of non-cross resistant
      chemotherapy programs or investigational programs such as high dose chemotherapy
      with autologous or allogenic bone marrow rescue. An appropriate management
      decision depends upon assessment of the disease and also on the impact of
      treatment side effects on the individual patients.

PMID- 8571736
TI  - [Characteristics and diagnostics of blood cell defects in paroxysmal nocturnal
      haemoglobinuria (NNH)].
AB  - In this review the data on glycosyl-phosphatidylinositol anchored protein
      deficiency occurring on different cells in paroxysmal nocturnal haemoglobinuria
      are presented. In addition different diagnostic methods in PNH are discussed.

PMID- 8571737
TI  - Analysis of 15 cases with platelet EDTA-dependent antibodies.
AB  - In 15 patients with thrombocytopenia EDTA-dependent platelet antibodies (IgM
      agglutinins active in 20 degrees C) were detected. These antibodies were found in
      patients with autoimmune diseases, infections and neoplasma as well as in healthy
      persons (including pregnant woman). In 10 persons pseudothrombocytopenia (PTCP)
      was diagnosed since the low platelet counts were found only in EDTA-blood, and
      the patients did not have bleeding symptoms. In 5 other cases EDTA-dependent
      antibodies were not the only cause of thrombocytopenia since the low platelet
      counts were also observed in the citrate-blood and occassionally the bleeding
      symptoms occurred; in 3 of them in addition autoantibodies were suspected. Due to
      the proper diagnosis of PTCP, in five patients unnecessary corticotherapy was
      discontinued, one person avoided splenectomy, in two patients previously
      postponed surgery was performed and one person could be passed for employment.

PMID- 8571738
TI  - Activated lymphocytes in the marrow cell suspension decrease the mafosfamide
      induced CFU-GM cytotoxicity.
AB  - The aim of the study was to assess whether other cells, besides erythrocytes, may
      influence the cytotoxic effect of mafosfamide (maf) during ex vivo bone marrow
      purging from residual tumor cells before autologous transplantation. It was shown
      that the presence of normal granulocytes, blast cells from acute myeloid leukemia
      patients (AML) and lymphoma cells from patients with chronic lymphocytic leukemia
      (CLL) during maf incubation did not change the maf-induced growth inhibition of
      CFU-GM. Similar observation was made in experiments with resting lymphocytes.
      However, when phytohaemagglutinin- and pokeweed mitogen-preincubated lymphocytes
      were present in the marrow cell suspension, significant decline of the maf
      related CFU-GM cytotoxicity was observed. These results suggest that besides
      erythrocytes also the activated lymphocytes in the marrow mononuclear suspension
      may change the final effect of maf purging.

PMID- 8571739
TI  - Can busulfan replace fractionated total body irradiation as conditioning regimen
      for allogeneic bone marrow transplantation in children with acute lymphoblastic
      leukemia.
AB  - The results of allogenic bone marrow transplantation (allo-BMT) in 26 children
      with ALL treated with the same initial- and relapse-BFM-protocols, but
      transplanted in different centers (Poznan, Wroclaw, Hannover) after conditioning
      with two different regimens have been compared. Ten children (6 in Poznan, 4 in
      Wroclaw) were conditioned for BMT with busulfan and cyclophosphamide when
      fractionated TBI (FTBI) was not available there. Sixteen children obtained FTBI
      and etoposide (11 in Hannover, where in children with ALL exclusively
      chemoradioconditioning regimen has been employed, and 5 in Poznan). It has been
      found, that the chemoconditioning procedure was probably less effective (5-year
      EFS 18%) than the regimen with FTBI (7-year EFS 60%). Therefore, TBI seems to be
      at this point still mandatory in pediatric ALL patients, unless combinations of
      chemotherapeutic drugs might be able to substitute the radiation in the future.

PMID- 8571740
TI  - [A relationship between the breakpoint of the bcr gene and some hematologic
      parameters in patients with chronic myelogenous leukemia].
AB  - We examined the hybrid bcr/abl mRNA present in 59 patients with chronic myeloid
      leukemia, using the reverse transcription method and polymerase chain reaction.
      Bcr/abl gene was found in 98% of patients. 60% of patients had b3a2 type of
      translocation, 40% type b2a2. Patients with b3a2 type had higher platelet count
      at diagnosis presentation than patients with b2a2. Other hematological data were
      similar in both groups.

PMID- 8571741
TI  - [Natural cytotoxicity of peripheral blood mononuclear cells in Herpes simplex and
      Varicella-zoster virus infections].
AB  - Natural cytotoxicity of peripheral blood was assessed in adults with recurrent
      Herpes labialis and in patients with Herpes zoster. CD16+ cells count,
      lymphocytes forming conjugates with K 562 cells count and NK activity in chromium
      release assay were measured. Decreased CD16+ cells count and depressed NK
      activity were found during latency of HSV infection. During reactivation of the
      infection lymphocytes forming conjugates count was increased. Functional
      activation of natural killing was noted in patients with herpes zoster in the
      acute phase of the disease. However, no differences between results of all NK
      tests after herpes zoster versus control group were found.

PMID- 8571742
TI  - [Detection of minimal residual disease in acute leukemias by immunophenotyping of
      bone marrow cells].
AB  - Minimal residual disease (MRD) can be detected only by sophisticated methods,
      e.g. immunologic. The purpose of the study was to detect MRD in leukemia patients
      (AL) being in hematological and clinical remission (CR) by immunophenotyping of
      bone marrow cells and to define the role of the immunologic method in the
      detection of MRD. Bone marrow samples from 31 patients with ALL and AML and from
      18 volunteers were taken several times. Staining of the cells was performed by
      double color immunofluorescence (IF) and double color immunoenzyme assay (APAAP).
      The detection of MRD was done by the comparison of the percent of positive cells
      between AL and normal cases. Each pair of the antigens (CD) was estimated in its
      usefulness in MRD detection. The statistical analyses were evaluated with a t
      Student's test.

PMID- 8571743
TI  - [Clinical significance and prognostic detection of minimal residual disease in
      acute leukemias].
AB  - The term minimal residual disease (MRD) describes leukemia cells present in bone
      marrow at a level below that detectable by conventional methodology in patients
      being in complete hematological and clinical remission (CR). The purpose of the
      study was, the detection of MRD in leukemia patients (AL-MRD+), the correlation
      between AL-MRD+ and the chosen hematological and clinical parameters and the
      follow up, and the prognosis. Bone marrow samples from 31 patients with ALL and
      AML, and from 18 volunteers were taken several times. Staining of cells was
      performed by double color immunofluorescence (IF), using flow cytometer and
      double color immunoenzyme assay (APAAP). The statistical analysis were evaluated
      with a t-Student's test and chi-squared test.

PMID- 8571744
TI  - [Concentrate of coagulation factor IX: viral validation of the thermoinactivation
      process].
AB  - The coagulation factor IX obtained at the Institute of Haematology and
      Transfusion in Warsaw was subjected to virological validation. Two lipide
      enveloped viruses were used: HSV-1 and Sindbis which may be a model for the
      viruses of B and C types in hepatitis. It was shown that heating of the freeze
      drying preparations at 80 degrees C during 72 hrs leads to full inactivation of
      the added model viruses.

PMID- 8571745
TI  - [Rosai-Dorfman syndrome in a 17 year old boy as a diagnostic problem of
      lymphadenopathy].
AB  - Rosai-Dorfman syndrome of Sinus Histiocytosis with Massive Lymphadenopathy is a
      benign disorder of unknown etiology which is characterized by proliferation of
      phagocytic-like cells that infiltrate tissues. We present here a case of a 17
      years old boy with the enlargement of the cervical lymph nodes who developed this
      disease. The diagnosis was established by the histopathological examination.
      There was no evidence of recurrence during the 18 months of follow up.

PMID- 8571746
TI  - [Diagnosis of arterial hypertension].
AB  - The intention of improving the efficiency of antihypertensive treatment, mainly
      regarding the reduction of excess morbidity and mortality in cardiovascular
      disease, offered an impressingly increasing variety of new therapeutical options
      within the last two decades. The anticipated success of this intensified effort
      also requires new approach to our diagnostic accuracy. Therefore not only the
      complete individually cardiovascular risk profile, but also the recently by
      national and international societies modified guidelines for intervention,
      regarding to blood pressure level and concomitant diseases, have to be taken in
      account. On the other hand the in the meantime wide-spread use of ambulatory
      blood pressure monitoring (ABPM) is not only able to provide valuable data
      concerning prognosis, but also is an undeniable important method distinguishing
      low risk groups such as the white coat hypertensives. Secondary hypertension
      actually is a rare condition of about 5% of all hypertensives. Nevertheless the
      appropriate diagnosis has to be established immediately as it is a potentially
      curable disease.

PMID- 8571747
TI  - [Diagnosis of endocrine-induced forms of hypertension].
AB  - High blood pressure is due to endocrine disorders in only a small fraction of
      hypertensive patients. However, the recognition of these conditions offers the
      potential chance to cure hypertension and hence to avoid secondary cardiovascular
      complications. It is therefore of pivotal importance for the group of patients in
      question.

PMID- 8571748
TI  - [New aspects in evaluating the hypertensive patient: measuring blood pressure in
      the physician's office--ambulatory blood pressure monitoring--blood pressure self
      measurement].
AB  - The "average" blood pressure of hypertensives, which is held responsible for the
      adverse effects of hypertension is poorly reflected by causal readings (CR),
      which are taken as a surrogate. CR do not only differ from average blood
      pressures, but also fail to give information on blood pressure variability.
      According to white coat effect and blood pressure variability a satisfying
      classification of severity and consecutively of prognosis cannot be done in an
      individual. Furthermore CR fail to inform us sufficiently about therapeutic
      effects in single patients. To improve we have to change to blood pressure
      judgements which are based on many instead of occasional readings. Ambulatory
      blood pressure monitoring (ABM) is a possibility to overcome this weakness.
      Compared to casual readings the average of the ambulatory readings is higher
      reproducible and does not depend on placebo treatment. In spite of this advantage
      a general substitution of CR by ABM is impossible because the number of equipment
      available is too small, nobody wants to cover the costs, the procedure is
      inconvenient, and up till now we miss guidelines how to proceed in the daily
      routine. Blood pressure self-monitoring is an additional way to improve the
      weakness of CR. The amount of blood pressure readings needed for a satisfying
      judgement of blood pressure are taken and registered by the patients. The self
      recorded data can be used as a valuable data base to calculate average blood
      pressure and blood pressure variability and drug effects. Mean values of twice
      daily recordings of a month are highly reproducible and do highly correlate to
      average ABM recordings of the day.

PMID- 8571749
TI  - [Refractory hypertension--principles of combination therapy].
AB  - "Non response" to treatment of hypertension may have different reasons: it may be
      "physician-related" ("white coat hypertension"), of "patient related" (poor
      adherence to prescribed medication, alcohol abuse, obesity) and it may really be
      a "resistant hypertension". In such cases one should search for a primary
      disease. If no such disease is found one should--according to the time-factor-
      wait for several weeks before increasing the dose; later on one should switch to
      another drug with a different mechanism of action and, if necessary, use a
      rational combination.

PMID- 8571750
TI  - Risk factors and differential antihypertensive therapies.
AB  - A less pronounced reduction in the incidence of coronary heart disease than in
      cerebrovascular events has been observed during antihypertensive therapy.
      Hypertension may not be the dominant risk factor for coronary heart disease as it
      is for cerebrovascular disease, and metabolic factors gain more importance. The
      reason for the differential effect of antihypertensive therapy could partly be
      explained by the adverse metabolic effects of some antihypertensive drugs which
      may thus attenuate the beneficial effects. When decision is made concerning
      antihypertensive treatment, it is imperative to assess the overall cardiovascular
      risk of the patient and take into account the possible impact on these factors of
      the different antihypertensive drugs.

PMID- 8571751
TI  - [Antihypertensive therapy and coronary heart disease: significance of the effect
      of concomitant cardiovascular risk factors].
AB  - Antihypertensive therapy as it was performed in the past has not provided the
      degree of protection against coronary heart disease as was originally predicted
      by epidemiologic evidence. An improvement of outcome of antihypertensive therapy
      can only be achieved if coronary risk is maximally reduced. Therefore, in
      treating hypertensive patients, one has to take care of a diligent search for the
      presence of other coexisting coronary risk factors, of a vigorous use of life
      style modifications (nondrug therapy), and of a greater individual selectivity of
      antihypertensive agents for initial and chronic use, preferring those that may
      provide additional benefits for other coexisting coronary risks.

PMID- 8571752
TI  - [Antihypertensive therapy in renal failure].
AB  - Hypertension can be a cause as well as a consequence of renal disease. Fluid
      overload or activation of the renin angiotensin system by glomerular ischemia
      leads to an elevation of systemic blood pressure in acute as well as chronic
      renal disease. Furthermore in the latter disorder an increased activity of the
      sympathetic nervous system as well as metabolic disorders contribute to
      hypertension. Accordingly antihypertensive therapy in patients with renal
      insufficiency is diverse. Additionally in chronic kidney disease one has to
      consider the variable effects of different antihypertensive drugs on intrarenal
      hemodynamics.

PMID- 8571754
TI  - Effects of respite care: a literature review.

PMID- 8571753
TI  - [Antihypertensive therapy in stroke: acute therapy, primary and secondary
      prevention].
AB  - Arterial hypertension represents the single most important treatable risk factor
      for stroke, therefore antihypertensive treatment is crucial. Observational
      studies have shown that in the acute phase of an ischemic stroke blood pressure
      is elevated during the first few days and helps to restore cerebral perfusion,
      activates collateral arterial supply and enhances the treatment goal of
      minimizing infarct size. Especially for acute ischemic strokes with stable
      deficits drug treatment of hypertension therefore is recommended only at systolic
      pressures of > or = 220 mm Hg or with diastolic pressures of > or = 120 mm Hg
      except when heart, lung or renal failure are also present. In primary prevention
      of stroke there is a large potential for hypertension treatment which reduces the
      relative risk by 42%. Especially elderly people with moderate hypertension should
      be treated. One vascular event per year can be avoided in 100 patient treatment
      years. Only scarce data exist on secondary prevention of stroke which show that
      hypertension treatment has a major importance for the modification of risk
      factors.

PMID- 8571755
TI  - Teaching the teacher: a preceptor-education program....

PMID- 8571757
TI  - "One day in the life of an author--episode one".

PMID- 8571756
TI  - Community care: walking the ethical tightrope.

PMID- 8571758
TI  - The experiences of family members of persons with Huntington's disease.

PMID- 8571759
TI  - Atraumatic recurrent posterior shoulder subluxation: review of the literature and
      recommendations for treatment.
AB  - Isolated atraumatic recurrent posterior subluxation of the shoulder (ARPS)
      constitutes 1% of all shoulder subluxations; it is therefore difficult for any
      single clinic to gain a large experience in treating this condition. Based on a
      review of the literature 83 cases of ARPS out of 237 reported cases with all
      types of posterior subluxation of the shoulder (185 patients) were analyzed. Most
      cases of ARPS occur between 11 and 20 years of age; they are frequently
      associated with changes such as dysplasia of the glenoid labrum or an alteration
      in the spinoglenoid angle. More than half of all ARPS occur bilaterally. The
      diagnosis is based on history, physical examination including tests of
      instability, or on techniques of dynamic examination (ultrasonography,
      arthroscopy). A plan of management related to the underlying etiology has been
      developed. At the first occurrence, cases of subluxation should be treated
      conservatively by kinesitherapy and physical therapy. Operative treatment is
      indicated when conservative management for at least 6 months has been
      unsuccessful and subluxation continues to occur during everyday activities, but
      it should never be instituted in patients with emotional disorders. The
      underlying pathologic lesion should determine the technique for shoulder
      reconstruction in atraumatic posterior shoulder subluxation. In cases in the
      atraumatic voluntary subgroup, surgery is indicated if conservative treatment
      fails and the voluntary component has been eliminated. In this subgroup, isolated
      soft tissue procedures have not been shown to produce good long-term results, and
      supplementary bony procedures are considered necessary. Conservative treatment
      exclusively is recommended in voluntary cases.

PMID- 8571760
TI  - Postoperative dropfoot after cementless total hip arthroplasty.
AB  - From 1989 through 1993, postoperative dropfoot occurred in seven patients after
      noncemented total hip replacement. After analysis of the records and a review of
      the literature the authors assume that cementless components may be a
      contributory factor to sciatic nerve palsy in total hip replacement, especially
      in combination with Low Molecular Weight Heparin.

PMID- 8571761
TI  - [Camptocormia or reducible lumbar kyphosis in elderly subjects. Apropos of 2
      cases of lipoid degeneration of the paravertebral muscles].
AB  - Two cases of "camptocormia" or progressive and reducible kyphosis acquired in the
      elderly are reported. This sagittal imbalance of the spine is induced by fatty
      involution of the paravertebral muscles. One case was symmetrical, the other one
      unilateral. This rare pathology should be considered during the spinal
      examination. Bony fusion is problematic owing to the muscular insufficiency. The
      primary treatment is medical, by strengthening and corticotherapy.

PMID- 8571762
TI  - Primary subacute osteomyelitis of the wrist in children.
AB  - The authors report 3 cases of subacute osteomyelitis of the distal radius and
      ulna, simulating a malignant bone tumor. The literature on this particular
      condition is reviewed.

PMID- 8571763
TI  - Augmentation of ventral derotation spondylodesis according to Zielke with double
      rod instrumentation. Preliminary report on two-year results of thoracolumbar
      curves.
AB  - The advantages of VDS according to Zielke with excellent 3-dimensional correction
      and shorter fusion levels in comparison to posterior instrumentation techniques
      are well known. A disadvantage is the necessity of long postoperative
      immobilization in a body cast or brace due to lack of primary stability. The aim
      of the VDS double-rod instrumentation is augmentation of the system with the
      possibility of postoperative treatment without plaster cast or braces. Following
      thoracolumbophrenotomy and ligation of the segmental vessels double-hole vertebra
      clamps are inserted. First VDS screws are placed in the posterior holes of these
      plates. With a 4-mm threaded compression rod correction is obtained by
      centripetal compressive forces on the nuts. Next VDS screws for the 5-mm threaded
      rod are inserted into the anterior holes of the vertebral clamps. The rod is
      implanted in a slightly compressive manner and augments the system. In a
      prospective study 8 patients, 4 with idiopathic and 4 with neuromuscular
      scoliotic deformities, underwent this surgical procedure and now have a follow-up
      of 2 years. Curves ranged from 45 degrees to 131 degrees Cobb angle. All patients
      were treated without plaster casts or braces postoperatively, but with only a
      semielastic vest for 4 to 6 months. Unusual intra- and postoperative
      complications have not been noted. Correction of the primary curve averaged 69.4%
      at follow-up. Tilt of the caudal end vertebra was corrected 75% to an average of
      6.3 degrees. Spontaneous partial correction of the upper secondary curve was
      noted in all cases. Rod fracture of the 5-mm rod without fracture of the 4-mm rod
      at this level was seen in 1 patient without loss of correction. Solid fusion was
      achieved at every level in all patients. The sagittal plane was not adversely
      affected by the instrumentation. However, larger patient numbers and a longer
      follow-up are necessary.

PMID- 8571764
TI  - Sagittal plane correction in "King-classified" idiopathic scoliosis patients
      treated with Cotrel-Dubousset instrumentation.
AB  - INTRODUCTION AND AIM OF THE STUDY: Whereas Harrington instrumentation (HI) has
      demonstrated satisfactory frontal plane correction, sagittal plane realignment is
      difficult. Sagittal plane control is reported to be easier with Cotrel-Dubousset
      instrumentation (CDI). This study was undertaken to determine if in our series
      sagittal realignment was achieved with CDI in idiopathic curves classified
      according to King. MATERIAL AND METHODS: Ninety-seven patients with idiopathic
      scoliosis classified according to King and treated with CDI underwent coronal and
      sagittal plane analysis by an unbiased observer. The sagittal curves were
      measured with the Cobb method from T4-T12 (normals: +25 to +40 degrees) and L1-L5
      (normals: -40 to -55 degrees). The thoracolumbar junction (TJ) was divided into
      an upper TJ (T10-T12) and a lower TJ (T12-L2) with normals between 0 and +10
      degrees for the former and 0 and -10 degrees for the latter. RESULTS: In all
      types of scoliosis with associated thoracic hypokyphosis a significant
      realignment could be achieved, ranging from 8 degrees in King 1 and 3 curves to
      19 degrees in King 4 curves. In normokyphotic curves no significant changes of
      the thoracic spine were measured postoperatively. Concerning the upper TJ,
      pathological lordosis was corrected by 7 degrees on the average, whereas
      correction of kyphosis ranged from 8 to 18 degrees Cobb. Pathologic kyphosis and
      hyperlordosis of the lower TJ showed a mean correction of 7 degrees and 11
      degrees, respectively. There was no significant direct influence of CDI on the
      sagittal plane of the lumbar spine. CONCLUSION: The data from this study suggest
      that correction in the sagittal plane can be achieved with CDI in King-classified
      scoliotic deformities.

PMID- 8571765
TI  - Elastofibroma dorsi: clinical and pathologic aspects of two cases.
AB  - Elastofibroma dorsi is a benign entity that occurs most often in the subscapular
      area in elderly women. It has been a subject of controversy whether elastofibroma
      is a true neoplasm or a reactive fibrous lesion that produces abnormal elastic
      fibers. A biopsy should be performed to rule out sarcoma in all cases, but
      definitive treatment only requires simple surgical excision. We report two cases
      of elastofibroma and discuss the most relevant clinical and pathologic aspects.

PMID- 8571766
TI  - The controversy of the biomechanics of the triangular fibrocartilage complex: a
      mathematical model to clarify the problem.
AB  - In the recent literature a controversy exists about the tension in the distal
      radioulnar ligaments during pronation and supination. A mathematical model
      supports the theory of Schuind and coworkers and indicates that the palmar distal
      radioulnar ligament is taut in supination.

PMID- 8571767
TI  - [Intra-osseous and intra-articular cyst of the knee. Apropos of a case associated
      with osteochondritis dissecans].
AB  - Subchondral bone cyst, intraarticular synovial cyst, and osteochondritis
      dissecans arising together are analyzed: this association has so far not been
      reported. If we accept the theory of a mechanical origin for subchondral bone
      cysts (leakage of joint fluid or intrusion of the synovial membrane through a
      breach in the cartilage), then the osteochondritis certainly provided the port of
      entry that allowed formation of the intraosseous synovial cyst in this patient.

PMID- 8571768
TI  - Rapidly progressive destruction of the hip. Case report and review of the
      literature.
AB  - A case of total destruction of the femoral head over a period of eight weeks is
      described. The diagnosis of avascular necrosis was made on the pathological
      examination. In the literature, four mechanisms of rapid destruction of the
      femoral head are mentioned.

PMID- 8571769
TI  - Persistent median artery in carpal tunnel syndrome.
AB  - Persistent median artery of the forearm and wrist is not very frequently
      observed. Only a few cases of persistent median artery thrombosis associated with
      compression of the median nerve in the carpal tunnel have been reported: in these
      cases symptoms arise acutely and surgery consists in the excision of the
      thrombosed arterial branch. In a patient with recurrent carpal tunnel syndrome,
      with a patent median artery and duplication of the median nerve, we performed
      neurolysis of the nerve and repositioning of the artery to the ulnar side.
      Electromyography, arteriography and clinical examinations performed six months
      later showed that irritative phenomena of the median nerve had regressed and the
      artery was still patent.

PMID- 8571770
TI  - Cerebral embolism during revision arthroplasty of the hip.
AB  - Cerebral embolism poses one of the most perplexing problems in cerebrovascular
      disease; fat emboli and marantic air emboli occur occasionally. However, the most
      common cause for a cerebral embolism is degenerative changes in the central
      arteries. The authors report the case of a 75-year-old female suffering from
      ischemic cerebrovascular disease of the left dominant hemisphere during a
      revision arthroplasty of the right hip (cementless Austin Moore hemiarthroplasty
      to a cemented Charnley total hip replacement); a cement gun was used to introduce
      the cement; both the induction of anesthesia and the surgical procedure were
      uneventful. The patient awoke slowly, and when awake she showed a combination of
      contralateral hemiplegia, and right hemianesthesia with global aphasia; the CT
      scan showed an ischemic lesion in the territory of the middle cerebral artery;
      during the following two weeks the patient showed complete recovery from the
      clinical syndrome. This complication must be recognized by every orthopedic
      surgeon, and a high clinical index of suspicion remains essential to early
      diagnosis.

PMID- 8571772
TI  - [Value of a direct approach to the calcaneum].
AB  - The authors describe an approach to the calcaneus: the incision follows the
      Achilles tendon and curves anteriorly between the lateral and plantar skin of the
      foot. The subtalar joint is opened using a Muller distractor, with one pin in the
      tibia and the other in the calcaneus. Sixty-one crush fractures of the thalamus
      were treated using this approach. There were 6 cases with skin problems; in 4
      cases the skin necrosis was limited. This approach is useful in all cases: it
      provides excellent exposure of the subtalar joint, making a precise reduction of
      the fracture possible. When a distractor is used, varus of the calcaneus should
      first be reduced.

PMID- 8571771
TI  - Contralateral median nerve autograft.
AB  - Interfascicular nerve autografting is a useful method to repair nerves with gaps,
      mainly if the removal of a nerve does not imply a defect to the donor area. Final
      results of peripheral nerve repair definitely depend on the size of the nerve
      gap, the level of the injury and the time elapsed from the time of injury until
      the nerve is repaired.

PMID- 8571773
TI  - Skin closure in hip surgery: subcuticular versus transdermal. A prospective
      randomized study.
AB  - A randomized parallel-group clinical trial was conducted between March 1991 and
      December 1993 to compare the effectiveness of subcuticular suture using
      absorbable material (Dexon) and continuous transdermal blanket suture using
      nonabsorbable material (silk) in hip surgery. Eighty patients (48 females and 32
      males) aged between 19 and 94 years (average 71.4 years) who underwent 97 hip
      operations were studied. Patients were followed up between 2 and 20 months. The
      two groups were evaluated with respect to infection rate, patient satisfaction
      with the scar, extra time and cost in removal of suture and the cosmetic
      appearance assessed by a plastic surgeon evaluating photos of patients' wounds
      using a specific scoring method without knowledge of the suturing method used.
      Five patients died during the study. There was no significant difference in
      superficial infection rate between the two groups (5% with positive
      bacteriological swab and 16% requiring extra antibiotics on clinical grounds). No
      deep infection was suspected in either group. The average score of patient
      satisfaction with the scar was 9.6/10 in the subcuticular group and 8.68/10 in
      the continuous mattress with a significant difference between the two groups (p <
      0.05). Cosmetic evaluation by the plastic surgeon using a 6-category scoring
      system showed a better cosmetic result in the subcuticular group with a
      significant difference (p < 0.01). An average of 17 minutes of extra nursing time
      was needed for removal of suture material in the nonabsorbable group in addition
      to the cost of the suture removal set. We conclude that absorbable subcuticular
      skin closure is an effective method and offers some advantages over the
      traditional transdermal suturing method in hip surgery.

PMID- 8571774
TI  - [Prevention of galactose-induced cataractogenesis in rats by salvianolic acid A].
AB  - Salvianolic acid A has been demonstrated to have efficient antioxidative and free
      radical scavenging effects. In the present experiments, the preventive effects of
      salvianolic acid A on galactose-induced cataract in rats were investigated.
      Dropping 0.05% salvianolic acid A in the eyes (two times a day) was found to
      delay the development of cataract. The contents of MDA and H2O2 in the cataract
      lens were decreased in salvianolic acid A treated rats. The protein and non
      protein thiols in the cataract lens of the salvianolic acid A treated rats were
      higher than those of control rats. In in vitro experiments salvianolic acid A was
      shown to inhibit aldose reductase activity. These results indicate that
      salvianolic acid A can prevent galactose-induced cataract by antioxidation and
      inhibition of aldose reductase.

PMID- 8571775
TI  - [Effects of tetrahydroprotoberberines on cytosolic free calcium in cultured rat
      single myocardial cells].
AB  - Effect of tetrahydroberberine (THB), l-tetrahydropalmatine (THP) and l
      stepholidine (SPD) were supposed to be related to the blocking of calcium influx.
      In this paper, using Fura-2/AM and AR-CM-MIC cation measurement system, the
      effects of THB, THP and SPD on cytosolic free calcium ([Ca2+]i) in cultured rat
      single myocardial cells were examined and compared with verapamil (Ver). THB, THP
      and SPD (10-100 mumol.L-1) were found to increase resting [Ca2+]i gently, which
      was not depressed by tetrodotoxin. THB, THP and SPD (1-100 mumol.L-1) were also
      shown to inhibit the KCl-induced [Ca2+]i elevation, the IC50 values of THB and
      SPD were 50.9 (95% confidence limits: 18.5-140) mumol.L-1 and 23.5 (95%
      confidence limits 7.6-73.4) mumol.L-1, respectively. THB, THP and SPD 30 mumol.L
      1 were also shown to inhibit the elevation of [Ca2+]i induced by high
      extracellular calcium and norepinephrine; but the inhibitory effects of these
      drugs were weaker than those of Ver. The three compounds showed no significant
      effect on ouabain induced [Ca2+]i increase. These results suggest that the
      inhibitory effects of THB, THP and SPD on [Ca2+]i in myocite by blocking voltage
      dependent calcium channels were similar but inferior to Ver.

PMID- 8571776
TI  - [Effects of gamma-aminobutyric acid on isolated dog cerebral arteries].
AB  - The present experiments were designed to investigate the effects of gamma
      aminobutyric acid (GABA) on isolated dog cerebral arteries (basilar artery). On
      addition of agonists phenylephrine 10 mumol.L-1, 5-HT 10 mumol.L-1, or KCl 25
      mmol.L-1, the isometric tension of the contraction increased 0.51 +/- 0.18 g,
      0.33 +/- 0.12 g and 0.57 +/- 0.16 g. After GABA at 50 mumol.L-1, the contraction
      was shown to decrease 0.27 +/- 0.15 g, 0.19 +/- 0.07 g and 0.17 +/- 0.06 g, the
      maximal relaxation were 45.49% +/- 20.4%, 58.60% +/- 12.96% and 27.75% +/-
      15.78%, respectively. But it showed no effect on the contraction induced by high
      concentration of KCl (45 mmol.L-1). GABA also showed a potent relaxation on the
      contraction induced by cold Krebs solution (T 28 +/- 0.5 degrees C). The finding
      suggest that GABA can inhibit the muscle tone induced by various agonists and
      cooling in isolated dog basilar artery.

PMID- 8571777
TI  - [Effects of guan-fu base a on experimental cardiac arrhythmias and myocardial
      contractility].
AB  - Guan-fu base A (GFA) is a terpenoid alkaloid isolated from the tuber of Aconitum
      coreanum in our institute. GFA (20-30 mg.L-1) reduced the ventricular tachycardia
      (VT) and ventricular fibrillation (VF) rate induced by K(+)-free and high Ca2+
      solution in Langendorf heart of rats. Pretreatment of conscious rats with GFA 2.5
      10 mg.kg-1 iv, increased the amount of beiwutine necessary to produce
      arrhythmias. Ouabain-induced VT in conscious dogs was reverted to sinus rhythm in
      1-2 min by iv GFA 9-10 mg.kg-1. GFA 10-20 mg.kg-1 iv was also found to be
      effective in protecting anesthetized dogs from atrial fibrillation induced by
      topical application of ACh. GFA 10 mg.kg-1 iv obviously decreased heart rate and
      prolonged the P-R interval, but slightly affected the myocardial contractility in
      anesthetized dogs. GFA showed no obvious effect on stroke volume and cardiac
      output in conscious dogs. In conclusion, GFA showed therapeutic and prophylactic
      effect on different models of experimental arrhythmias without causing marked
      effect on myocardial contractility.

PMID- 8571778
TI  - [Effect of the conjugate composed of a human monoclonal antibody and
      pingyangmycin on mammary cancer].
AB  - To avoid or reduce the induction of human anti-mouse antibody reaction, it is
      important to use human antibody for the preparation of therapeutic
      immunoconjugate. CM1, a human monoclonal antibody directed against mammary
      cancer, was linked to pingyangmycin (PYM), an antitumor antibiotic identical to
      bleomycin A5 currently in clinical use, employing Dextran T-40 as an intermediate
      agent. As determined by clonogenic assay with mammary cancer CAMA cells, the IC50
      values for CM1-PYM conjugate and free PYM were 0.35 mumol.L-1 and 4.0 mumol.L-1,
      respectively. Mammary cancer CAMA was transplanted sc in nude mice. Peritumoral
      injection of CM1-PYM conjugate at doses of 1.25 mg.kg-1 and 2.5 mg.kg-1 inhibited
      the growth of CAMA xenograft by 86% and 95% (P < 0.01), whereas the injection of
      equivalent doses of free PYM inhibited CAMA xenograft by 49% and 58% (P < 0.05),
      respectively. CM1-PYM conjugate showed remarkable suppression on CAMA xenograft
      and the inhibitory effect of CM1-PYM conjugate was much higher than that of free
      PYM. By histo-pathological examination, no toxic changes were found in the heart,
      lung, liver, intestines, kidney, spleen and bone marrow of the CM1-PYM- or PYM
      treated animals. These results suggest that local administration of the
      immunoconjugate composed of a human monoclonal antibody and pingyangmycin is
      highly effective and the conjugate may be useful in therapy for human breast
      cancer.

PMID- 8571779
TI  - [On-line monitoring of nitrofurantoin in urine of rabbit by a flow-injection
      system with a fiber-optic chemical sensor].
AB  - A flow-injection system for monitoring of nitrofurantoin (NFT) in rabbit urine
      that makes use of a kind of fiber-optic chemical sensor is presented. The NFT
      sensitive optrode was combined with a membrane onto which was immobilized
      pyrenebutyric acid (PBA) as a fluoroprobe. The NFT concentration was determined
      via dynamic quenching of the fluorescence of PBA. The average recovery was 96.5%
      102.9%. The relative standard deviations for within-day and between-day were 3.1%
      3.7% and 1.6%-3.8% respectively. The calibration curve was linear in the range
      from 2 micrograms.ml-1 to 100 micrograms.ml-1 with r = 0.9983. The detection
      limit of this method was 0.74 microgram.ml-1. The urine drug concentration-time
      course in rabbit after oral administration conformed to a one compartment open
      model with a first order absorption phase. Mean T1/2 value was 0.75 +/- 0.14 h.
      The selectivity was affirmed by HPTLC.

PMID- 8571780
TI  - [HPLC method for determination of lorcainide hydrochloride in human serum].
AB  - An analytical method was established for determination of lorcainide
      hydrochloride concentration in serum using high performance liquid chromatography
      (HPLC). The stainless steel column was 200 mm x 5.0 mm ID, packed with YWG
      C18H37, 5 microns. The mobile phase consisted of methanol-water-0.625 mol.L-1
      ammonium acetate. (86:13:1 v/v), adjusted to the pH 8.0 with ammonium hydroxide.
      The flow rate was 1 ml.min-1, using diltiazem as internal standard.
      Chromatography was performed with ultraviolet detector at 226 nm. The recoveries
      of lorcainide hydrochloride at 40, 200 and 400 micrograms.L-1 were 95.85%,
      100.63% and 100.09%, respectively. The within-day and day-to-day RSD of the
      determinations at concentrations of 100, 200, 400 and 800 micrograms.L-1 were
      less than 7%. Linear calibration curve for lorcainide hydrochloride was measured
      within the range of 20 to 800 micrograms.L-1 with correlation coefficient of
      0.9996. The detection limit was 5 micrograms.L-1 in serum. The HPLC method
      described is suitable for clinical monitoring and pharmacokinetic study of
      lorcainide hydrochloride.

PMID- 8571781
TI  - [Study on metabolite of 5-ethyl-5-(para-fluorobenzoylpropyl) barbituric acid in
      rabbits].
AB  - The metabolite of 5-ethyl-5-(p-fluorobenzoylpropyl) barbituric acid (coded as F-B
      1) in rabbit has been separated with HPLC. UV-spectra of F-B-1 and its metabolite
      obtained with DAD, in combination with EI-MS and CI-MS of F-B-1, its metabolite
      and their derivatives were examined. Possible structure of the metabolite was
      obtained. Possible metabolic way of F-B-1 is the reduction of carbonyl on the
      benzene ring with formation of hydroxyl group. This was further confirmed by
      identity of HPLC and MS behavior of the metabolite and NaBH4 reductive product.
      In the structure of the latter, the carbonyl on the benzene ring was reduced, as
      proved by NMR (1H-NMR and 13C-NMR) spectra.

PMID- 8571782
TI  - [Feasibility assessment of skin permeation for the local anesthetic lidocaine].
AB  - In this paper, the feasibility of skin permeation for lidocaine and pressure
      sensitive adhesive (PSA) tape formulation containing lidocaine for skin local
      anesthetic were assessed. Firstly, in vitro skin permeation of the molecular and
      ionic forms of lidocaine from water and silicone fluid suspensions was measured
      using a side-by-side two diffusion cells and excised hairless rat skin. Secondly,
      PSA tape containing lidocaine was prepared by a general casting method using
      styrene-isoprene-styrene block copolymer. The in vitro release and skin
      permeation were evaluated and compared with that of Japan marketed xylocaine
      jelly. The effect of lidocaine concentration on the steady-state flux of skin
      permeation from 10% to 60% lidocaine PSA tapes was also evaluated.

PMID- 8571784
TI  - Mentality and Behaviour in Neurosurgery. Proceedings of the Convention of the
      Academia Eurasiana Neurochirurgica. Seoul, Korea, September 16-19, 1992.

PMID- 8571783
TI  - Anti-inflammatory compounds isolated from Menyanthes trifoliata L.

PMID- 8571785
TI  - Normality and abnormality in behavioural aspect.

PMID- 8571787
TI  - Ultimate reality in Won-Hyo. Reflection on the problem of religion and behaviour.

PMID- 8571786
TI  - Hormones and behaviour.

PMID- 8571789
TI  - Japanese mentality and behaviour--based on the indigenous Japanese culture.

PMID- 8571788
TI  - The motivation of addiction.
AB  - The addict pursues the drug effect despite its damaging impact. The aberration
      results from the side-tracking of a mood-dominated activity, which utilises
      automatic mechanisms beyond conscious introspection to regulate the pursuit of
      pleasure. The indirect nature of the mechanism creates the potential for its
      subversion. Drug use, for the non-addicted as well as the addict, bypasses the
      primary purpose of the pleasure principle, the motivation to achieve success.
      Instead, drug use produces pleasure on demand. The addict abandons the effort of
      striving for a goal, which has an uncertain chance of success, in preference for
      the certainty of the drug-induced pleasure. The sequence of unpleasure following
      pleasure, each proportional to the other, brings each response to a timely end
      and so sets in train renewed effort to achieve success and the chance of yet
      another bout of pleasure. The sequence delivers pleasure only on condition of
      prior payment or, in the case of drug use, "trip now and pay later". The bipolar
      nature of the pleasure principle draws comparison to a similar bipolarity
      extending throughout the structure and function of existence.

PMID- 8571790
TI  - Mentality and behaviour of neurosurgeons and patients in China.

PMID- 8571791
TI  - Mentality and behaviour in India.
AB  - Based on a historical survey of the origins and development of the Hindu religion
      and its absorption of Buddhism the author outlines that tolerance, gentle
      behaviour, profound optimism and a lack of obsession with time are the main
      features of Indian mentality and behaviour. But with industrial revolution,
      urbanisation and population explosion many old values have been eroded and even
      aggression of different degrees found its way into the Indian psyche.

PMID- 8571792
TI  - Mentality and behaviour of a Mediterranean neurosurgeon.

PMID- 8571794
TI  - Differences in personality between a medical and a surgical practitioner, and
      between a medical neurologist and a surgical one.

PMID- 8571793
TI  - Mentality and behaviour of the central European.

PMID- 8571795
TI  - The personality of the neurosurgeon.

PMID- 8571796
TI  - The neurosurgeon in the medical and civil society.

PMID- 8571797
TI  - Questionnaire regarding the neurosurgeon's behaviour.

PMID- 8571798
TI  - The unforgettable character of teachers in neurosurgery.

PMID- 8571799
TI  - Character and behaviour of teachers in neurosurgery from a Japanese perspective.

PMID- 8571801
TI  - [What do registries offer to clinicians?].

PMID- 8571800
TI  - Components of character and behaviour of teachers in neurosurgery.

PMID- 8571802
TI  - [Renal and ureteral complications of urethral stenosis].
AB  - This paper analyzes the renal and ureteral complications caused by urethral
      stenosis. A total of 180 patients with stenosis, 175 males and 5 females, were
      reviewed. There were 55 renal-ureteral complications in 37 patients (20.55%). In
      order of frequency, complications were as follows: renal failure (36%),
      ureterohydronephrosis (33%), chronic pyelonephritis (16%), vesico-ureteral reflux
      (11%), and post-obstructive renal annulment (4%). Most complications were
      reversible. However, renal function impairment was irreversible in 3 cases due to
      I.R.C., as well as in 2 cases due to post-obstructive renal atrophy-annulment.
      Nine patients showed chronic pyelonephritis morphological changes. Urinary
      infection occurred in 28 patients (76%), and in 50% of them was due to ureolytic
      germs. The best procedure to treat these complications is based on a correct
      prevention, eradicating the associated urinary infection and correcting the
      causative obstructive problem. Nonetheless, surgery was required in 5 patients
      (13.50%) and extracorporeal lithotripsy for the lithiasis associated to stenosis
      in other 5 patients (13.50%). We conclude that although those complications have
      a high incidence, their ultrasound diagnosis is easy and the prognosis reversible
      once the stenosis is corrected. Risk factors for development are: male sex, the
      sixth decade of life and a long evolution stenosis associated to urinary
      infection. Finally, a review of the scarce literature on this frequent but
      forgotten chapter of obstructive uropathy is made.

PMID- 8571803
TI  - [Role of tissue polypeptide antigen as a marker in bladder cancer].
AB  - Presentation of a review of TPA serum levels in 207 patients, 160 of which had
      vesical carcinoma. This population comprises 37 patients who had suffered vesical
      carcinoma but whom, at entry in the study, did not display clinic evidence of
      that: 11 patients with benign vesical pathology; 84 patients with primary vesical
      tumour, and 76 patients with relapsing vesical tumour. Tumoral staging resulted
      in 72 Ta, 49 T1, 10 T2, 14 T3, and 15 Ta. Distribution with regard to degree of
      differentiation was as follows: 52 GI, 61 GII and 40 GIII. Sensitivity of serum
      TPA in our series was 39% and specificity 94%. When tumours were subdivided into
      surface and infiltrant tumours, sensitivity was 28% and 72% respectively (p <
      0.01). Patients presenting normal levels of serum TPA took longer to relapse than
      those who had high levels. Mean time to relapse was 17 months for the first
      group, and 12 months for the second group. Serum TPA increased its performance
      with carcinomas of higher grade and stage, but it does not have enough
      sensitivity to be considered a useful marker in low stages. However, serum TPA
      relationship to the tumour's invasive degree and the disease-free interval are an
      indication for their likely use as a prognostic factor to delimit the groups with
      higher risk of relapse.

PMID- 8571804
TI  - [Management of non-functioning renal graft].
AB  - On a series of 315 consecutive Renal Transplants (RT), the authors analyze the
      effects from any situation capable of causing the graft's renal failure, whether
      accompanied or not of oligoanuria. To begin with, the exploratory approach
      promoted by the ?non-functioning kidney? is established recognizing three typical
      stages depending on the time of appearance: early, medium-term and long-term. The
      breakthroughs obtained in the prevention of Acute Tabular Necrosis (A.T.N.) are
      verified through the use of the receptor's hyperhydration, as well as the good
      results in the treatment of rejection since the arrival of Cyclosporin and the
      recent introduction of OKT3. Chronic rejection, is, today, the major cause of our
      transplantectomies (TX), since our attitude towards the exeresis of all
      irreversibly non-functioning grafts is well known. Vascular thrombotic problems
      have a very high percentage of losses among affected kidneys. Little can be done
      once the problem arises. Prevention is the best weapon available and special
      attention should be paid to the meticulousness of bank surgery and the suitable
      final positioning of the organ in the fossa iliaca, having into account the
      highly close relationship between this problem and the pathological and
      iatrogenic anomalies displayed by the organs to be transplanted in their arterial
      tree. The excretory tract problems are repaired in 83% cases, but the rest may
      even result in the loss of the kidney. In these complications, early surgery is
      the best way to avoid subsequent amputation surgery.

PMID- 8571805
TI  - [Brucellar orchitis. Report of a series of 16 cases].
AB  - A retrospective study of orchiepididymitis, diagnosed and admitted to our Unit
      over the 1989-94 period was conducted. there were 125 orchiepididymitis, of which
      16 (12.8%) had a brucellar etiology, and three had simultaneously become
      abscessified (18.75%). Considering that our working area is located within an
      endemic region, and even more, our province has the country's highest incidence
      rate (112.8/100000 inh.), this prompted us to study the conditions' morbidity in
      the testicular location, while we make a superficial revision of this disease.
      Brucellar orchitis is a diagnostic option to be taken into account in endemic
      regions, and the clinical picture associated to the orchiepididymal process
      should make us suspect its diagnosis and trigger follow-up of these patients.

PMID- 8571806
TI  - [Epidemiology of urinary lithiasis in la Ribera de Navarra (I)].
AB  - An epidemiological study on the lithiatic disease (LD) was conducted in 'La
      Ribera de Navarra' over a two year-period, based on the series from the Reina
      Sofia Hospital in Tudela. Between May 1988 and May 1990 we gathered 785 cases.
      This paper analyzes the hospitalization incidence, risk factors such as age, sex,
      familial and personal background of lithiasis, consumption of drugs., etc. A
      description is made of the geographical, geological, climatic conditions,
      composition of water, and other characteristics, as well as the clinical
      features. Incidence of LE in this Area V of Navarra is high, 5.1 per thousand
      inhabitants/year, being uncommon in children but frequent in adults: 7.92 per
      thousand men/year and 4.97 per thousand women/year, with a male/female ratio of
      1.52. There is a predominance of women over the early decades of life, the M/F
      ratio being 0.40 for the 15-24 years range. 19.61% of patients have a familial
      background of LE, the father being the most affected relation. Around 53.79% have
      been affected by LE. The factor most commonly correlated to frequency is the
      distance to the hospital and the rate of admission to the emergency service by
      area. No correction was noted to water hardness or weather differences. The
      greater incidence takes place during the summer and the lowest in the autumn.

PMID- 8571807
TI  - [Late metastasis in thyroid gland after nephrectomy for renal clear cell
      carcinoma].
AB  - Renal carcinoma natural history is unpredictable. Spontaneous metastases
      regression after nephrectomy, as well as late recurrence are suggestive of this
      peculiar human neoplasm. tumor metastases localized to thyroid gland are uncommon
      in clinical practice; and carcinoma of the kidney, breast, lung, melanoma and
      gastrointestinal tract tumors are responsible for the majority of them. This
      paper reports on a patient with metachronous thyroid gland metastases after
      fourteen years of renal carcinoma nephrectomy, with one year after
      hemithyroidectomy recurrence on cervical striated muscle followed by surgical
      excision. Therapeutical aspects are briefly reviewed in literature, emphasizing
      surgical treatment and the need of all-life follow-up, with more alert attitude
      toward thyroid gland after renal cell carcinoma nephrectomy.

PMID- 8571808
TI  - [Primary mucinous adenocarcinoma of the prostate].
AB  - Contribution of a new case of prostatic mucinous adenocarcinoma of primary
      origin. Diagnosis was established by histochemical techniques alcian blue, PAS
      and alcian-PAS) processing the fragments from the prostate transurethral
      resection (PTUR). Neither the existence of extraprostatic tumoration, local
      infiltration, or metastasis was recognized. No correlation between preoperative
      prostatic acid phosphatase (PAP) (50) and prostatic specific antigen (PSA) values
      (3ng/m) was evidenced. After radical prostatectomy both markers remain undetected
      one year after surgery.

PMID- 8571809
TI  - [Giant cell leiomyosarcoma of the spermatic cord: a report].
AB  - Presentation of the case of one patient with a leiomyosarcoma of the spermatic
      cord with presence of numerous giant cells, a remarkably unusual finding.
      Presence of this type of cells, as well as their positivity for histiocytic
      markers in immunohistochemical staining, raise considerable problems for the
      differential diagnosis of this neoplasia with malignant fibrous histiocytomas,
      which probably requires a different, more aggressive therapeutical approach.

PMID- 8571810
TI  - [Bladder leiomyoma: a new case for the current caseload].
AB  - Vesical leiomyoma is a benign mesenchymal tumor that rarely involves the bladder
      and makes about 1.5% of all vesical tumors. A new case is presented and aspects
      concerning clinical, diagnostic and surgical issues are examined. The paper
      includes a revision of the available literature on the topic.

PMID- 8571811
TI  - ["Economic aspects of the treatment of renal lithiasis". Round Table, VII Meeting
      on Urolithiasis and Urinary Endoscopy. Proceedings and abstracts].

PMID- 8571812
TI  - Mutation and cancer: a personal odyssey.

PMID- 8571813
TI  - Molecular pathogenesis of AIDS-related lymphomas.

PMID- 8571814
TI  - HLA class I antigens in human tumors.

PMID- 8571815
TI  - Molecular epidemiology of Epstein-Barr virus infection.

PMID- 8571816
TI  - Oncogenic role of "master" transcription factors in human leukemias and sarcomas:
      a developmental model.

PMID- 8571817
TI  - Scatter factor and angiogenesis.
AB  - Scatter factor (hepatocyte growth factor) is a mesenchyme-derived cytokine that
      stimulates motility, proliferation, and morphogenesis of epithelia. These
      responses are transduced through the c-met protooncogene product, a transmembrane
      tyrosine kinase that functions as the SF receptor. SF is a potent angiogenic
      molecule, and its angiogenic activity is mediated primarily through direct
      actions on endothelial cells. These include stimulation of cell motility,
      proliferation, protease production, invasion, and organization into capillary
      like tubes. SF is chronically overexpressed in tumors, suggesting that it may
      function as a tumor angiogenesis factor. SF production in tumors may be due, in
      part, to an abnormal tumor-stroma interaction, in which the tumor cells secrete
      factors (SF-IFs) that stimulate SF production by tumor-associated stromal cells.
      Studies suggest a link between tumor suppressors (antioncogenes) and inhibition
      of angiogenesis. We hypothesize that tumor suppressor gene mutations may
      contribute to the activation of an SF-IF-->SF-->c-met pathway, leading to an
      invasive and angiogenic tumor phenotype. Modulation of this pathway may,
      ultimately, provide clinically useful methods of enhancing or inhibiting
      angiogenesis.

PMID- 8571818
TI  - Role of VEGF-flt receptor system in normal and tumor angiogenesis.

PMID- 8571819
TI  - Pathways of chromosome alteration in human epithelial cancers.

PMID- 8571821
TI  - The clinical relevance of basic science: a surgeon's perspective.

PMID- 8571820
TI  - Genetics of murine lung tumors.

PMID- 8571822
TI  - Developmental aspects of excitation contraction coupling in urinary bladder
      smooth muscle.

PMID- 8571823
TI  - Congenital bladder obstruction: research strategies and directions.
AB  - The clinical significance of congenital bladder obstruction is evident to those
      who deal with children suffering from severe bladder dysfunction and renal
      failure. It is a lifelong effect often requiring complex surgical reconstruction
      and renal transplantation. CBO also represents an important pathophysiologic
      process with relevance to other organ systems in which hypertrophic and fibrotic
      processes occur. CBO occurs in a dynamic and developing organ in which function
      and development are interdependent. Alterations of one will induce alterations in
      the other which then affect the first. Multiple levels of organization are
      involved and relevant, from the cell to the whole bladder as a part of the
      organism. Functional and developmental changes have been demonstrated in models
      of CBO. Much attention has been focused on the connective tissue compartment of
      the bladder due to its important role in determining bladder compliance
      characteristics. Preliminary findings suggest that connective tissue remodeling
      may be affected by alterations in the balance of the regulatory mechanisms of
      collagen degradation. Further studies should be able to define these alterations
      and may permit specific modulation of these mechanisms.

PMID- 8571824
TI  - Extracellular matrix update--overview.

PMID- 8571825
TI  - Is collagen remodeling associated with bladder obstruction?

PMID- 8571826
TI  - Regulation of matrix metalloproteinases during extracellular matrix turnover.

PMID- 8571827
TI  - Elastic fibers and their role in bladder extracellular matrix.

PMID- 8571828
TI  - The collagens and their urologic implications.

PMID- 8571829
TI  - Changes in bladder extracellular matrix--overview.

PMID- 8571830
TI  - Matrix changes in the bladder associated with normal aging.

PMID- 8571831
TI  - The role of proteoglycans in bladder structure and function.

PMID- 8571832
TI  - Cultured bladder cells and their response to mechanical strain.

PMID- 8571833
TI  - Electrical properties of obstructed guinea pig bladder.

PMID- 8571834
TI  - Alterations in extracellular matrix gene expression in normal versus non
      compliant human bladders.

PMID- 8571835
TI  - Regenerative bladder augmentation: a review of the initial preclinical studies
      with porcine small intestinal submucosa.

PMID- 8571836
TI  - The effects of high urinary potassium concentration on pelvic nerve
      mechanoreceptors and 'silent' afferents from the rat bladder.

PMID- 8571837
TI  - Muscarinic receptor subtypes in normal, fetal, and gravid rabbit bladder, heart
      and uterus.
AB  - In the rabbit bladder, pregnancy has been shown to induce a significant decrease
      in both muscarinic receptor density and response to muscarinic stimulation.
      Neonatal rabbit bladders have a high muscarinic receptor density and contractile
      response to bethanechol stimulation. The bladders from 7 gravid rabbits, 7 age
      matched virgin controls, and 32 fetal rabbits of 3 week gestation were studied.
      Compared to control tissue, filtration binding demonstrated receptor density to
      be 24.3% lower in gravid bladder dome, 41.2% lower in gravid bladder base, and
      114.8% higher in fetal bladders. While total receptor density was not different
      from control in gravid heart, fetal hearts showed a 2.5 fold increased receptor
      density. There was also a 61% reduction in muscarinic receptor density in the
      gravid uterus. Immunoprecipitation assays using muscarinic receptor subtype
      specific antisera were used to measure the relative levels of m1, m2, m3 and m4
      receptors. The m2 receptor was the predominant subtype in the bladder and uterus,
      and the only subtype detected in rabbit heart. The m3 receptor protein was also
      present, but in lower levels in the bladder and uterus. The m1 and m4 receptors
      were not detected in any of the tissues studied. Furthermore, the relative
      percent of each receptor did not statistically change for the gravid or fetal
      rabbit bladder, uterus, or heart, when compared to its control. Differences in
      the contractile response to cholinergic stimulation of the gravid bladder and
      uterus, and of the fetal bladder then, can be attributed to changes in muscarinic
      receptor density and not to changes in receptor subtype.

PMID- 8571838
TI  - Fetal bovine bladder: physiology and pharmacology.

PMID- 8571839
TI  - Two mathematical models predict the variation in capacity and compliance of
      hypertrophied bladders.

PMID- 8571840
TI  - The effect of cholinergic stimulation on cultured smooth muscle cells.
AB  - OBJECTIVE: To assess the role of cholinergic angonists and antagonists on the
      growth control of cultured rabbit detrusor smooth muscle cells. DESIGN: Dosage
      dependent growth curve analysis of smooth muscle cells in standard media to
      bethanechol and atropine at concentrations from 1 x 10(-5) to 1 x 10(-9) mMol.
      RESULTS: Exogenous exposure to bethanechol results in a significant dose
      dependent increase in total cell number over a 10 day period. At a concentration
      of 1 x 10-6 and 1 x 10-5 mMol a 20% to 50% growth increase is noted. Exogenous
      atropine at all concentrations decreased growth by approximately five fold.
      CONCLUSIONS: The exogenous application of muscarinic cholinergic agonists and
      antagonists can significantly effect bladder muscle cell growth in vitro. The
      mechanism of growth control through these pharmacological receptors remains to be
      elucidated.

PMID- 8571841
TI  - Autologous periurethral fat injections for the creation of bladder outlet
      obstruction.

PMID- 8571842
TI  - Metabolism of detrusor smooth muscle in normal and obstructed urinary bladder.

PMID- 8571843
TI  - Bladder outlet obstruction--an overview.

PMID- 8571844
TI  - The neuronal response to bladder outlet obstruction, a role for NGF.

PMID- 8571845
TI  - Contractile proteins and their response to bladder outlet obstruction.

PMID- 8571846
TI  - Molecular aspects of bladder outlet obstruction.
AB  - In an animal model of obstruction, increasing load induces significant smooth
      muscle hypertrophy which is associated with a down-regulation of myosin heavy
      chain expression. This undoubtedly contributes to the decreased smooth muscle
      contractility seen in this model. Moreover, obstruction-induced hypertrophy leads
      to the development of a dedifferentiated smooth muscle phenotype, as evidenced by
      a revision of the cell to fetal (of non-muscle) gene expression patterns. Similar
      alterations are seen in atherosclerotic vessels and other pathologic smooth
      muscle systems. In these systems, dedifferentiation is also associated with
      significant alterations in extracellular matrix expression. It seems likely that
      obstruction in the bladder induces dedifferentiation of the smooth muscle cell
      which alters contractility as well as extracellular matrix expression, leading to
      altered bladder performance and decreased compliance.

PMID- 8571847
TI  - Bladder function in experimental outlet obstruction: pharmacologic responses to
      alterations in innervation, energetics, calcium mobilization, and genetics.
AB  - The two functions of the urinary bladder is to store urine at low intravesical
      pressures, and to periodically expel the urine through a coordinated contraction
      of the bladder and relaxation of the urethra. To a large extent, urinary bladder
      function depends upon the underlying structure of the organ as a whole,
      particularly on the inter-relationships among the smooth muscle, connective
      tissue, and neuronal elements. An alteration in the ratio of connective tissue to
      smooth muscle, for example, can significantly alter compliance and functional
      capacity, structurally impairing the bladder's ability to empty efficiently and
      fully. Thus, a change in structural compartmentation can affect bladder function
      independent of autonomic receptor density, response to receptor stimulation, and
      the contractile capabilities of the smooth muscle elements. Similarly, a
      selective alteration in either the afferent or efferent innervation of the
      bladder or urethra can induce significant alterations in the structural
      interrelationships between smooth muscle and connective elements. In addition,
      the bladder responds rapidly to alterations in urine volume and urethral
      resistance with marked changes in bladder and urethral structure and function,
      and these changes are under the controls of specific genes that are known to
      control cellular growth, hypertrophy, and hyperplasia. A knowledge of the
      mechanisms that control the response to specific forms of stress may lead to
      novel therapies for specific disease states.

PMID- 8571848
TI  - Developmental physiology--overview.

PMID- 8571849
TI  - Fetal lower urinary tract physiology: in vivo studies.
AB  - Fetal lower urinary tract function is under continuous maturation throughout
      gestation and is an integrated neurophysiologic event by late gestation.
      Preliminary in vivo study suggests that peripheral and central nervous system
      regulation of micturition occurs in utero, and that these events can be modulated
      pharmacologically and through external stimulation. Normal bladder function in
      utero is essential to normal development of the entire fetus, and in utero
      modulation of bladder dysfunction may be feasible as our understanding and
      diagnostic acumen increase.

PMID- 8571850
TI  - Fetal bovine compliance changes.

PMID- 8571851
TI  - [Active oxygens and free radicals in the eye diseases].

PMID- 8571852
TI  - [Trabecular meshwork and elastin].
AB  - Evidence that elastic fibers with elastin exists in the trabecular meshwork (TM)
      and play an important role in aqueous outflow resistance is presented. The
      elastic fibers consist of abundant microfibrillar components containing
      glycoproteins and amorphous components containing elastin. If TM tissues are
      digested with elastase, the cells composing trabecular sheets and Schlemm's canal
      are separated with a decrease of elastin and come in contact with each other with
      reproduction of elastin. When the anterior segments of eyes are perfused with
      elastase, the intraocular pressure drops with a decrease of outflow resistance. A
      large quantity of elastin exists in fine fibrils lying underneath the trabecular
      wall of Schlemm's canal in primary open angle glaucoma (POAG) eyes, in
      pseudoexfoliation (PE) materials of PE glaucoma eyes and in basement membrane and
      fine fibril-like materials of steroid glaucoma eyes. In congenital and juvenile
      glaucoma eyes, however, instead of elastin, fibronectin localizes in basement
      membrane and fine fibril-like materials. When TM tissues respond to steroid
      hormone, the tissues synthesize and secret microfibrils and elastin, components
      of the elastic fibers. Elastin gene expresses in human TM. Orally administered
      elastase is transferred in aqueous humor and digests elastin in TM. Therefore it
      is possible that such a drug decreases the outflow resistance of glaucoma eyes.

PMID- 8571853
TI  - [The oxidative stress in the cataract formation].
AB  - The lens of the eye is an avascular tissue surrounded by fluids such as the
      aqueous humor and vitreous body, with one side facing toward the outside of the
      body. We investigated peroxidative reactions occurring in cataractous lenses,
      examining changes within the lens tissues as well as in the surrounding
      environment. 1. Peroxidative reactions in lenses. 1) Aging and peroxidative
      reactions. The activity of superoxide dismutase (SOD) began to decrease in the
      lenses of rats at six months of age. Moreover, the level of lipid peroxide
      increased significantly in the lenses of rats at 24 months of age. Lipoproteins
      became increasingly oxidized with age. The levels of Na+, K+, and Ca++, ions that
      are important to the maintenance of membrane function, also varied significantly
      with age. In the lenses of six-month-old Senescence Accelerated Mice (SAM), there
      was a marked decrease in the ability of scavenge active oxygen and a marked
      increase in the amount of lipid peroxide. In human lenses, the level of
      autofluorescence increased as the lens fiber structure changed with age. 2)
      Generation of free radicals inside the lens. We verified that HO. and ascorbic
      acid radicals were being generated inside cataractous lenses using electron spin
      resonance (ESR). 3) Changes in oxidation-related substances in cataractous
      lenses. Senile cataractous lenses and diabetic cataractous lenses were classified
      as four types, cortical, nuclear, posterior subcapsular, and mature. In
      cataractous lenses from all types of diabetic patients, the levels of glucose,
      glycated protein, and lipid peroxide were higher than in senile cataractous
      lenses. Among the four types of cataracts, the accumulation of peroxides was the
      greatest in the nuclear type both diabetic and senile cataractous lenses. 4)
      Transitional metals. Iron ions and copper ions existed in lens tissue. In
      particular, the subepithelial region of the lens stained strongly for copper
      ions. The increased level of copper ions in cataractous lenses is likely to be
      related to the increased peroxidation in this tissue. 5) Changes in membrane.
      Lowered levels of phospholipids and a higher degree of saturation of fatty acids
      were observed in senile cataractous lenses as compared with normal lenses. The
      increased saturation of fatty acids indicated that there was a damage to the
      membrane structure due to peroxidative reactions. The receptors for low density
      lipoprotein (LDL) were shown to exist on the epithelium of normal lenses. Acetyl
      LDL, a denatured lipoprotein was incorporated into senile cataractous lenses but
      not into normal lenses, suggesting that the barrier function of the membrane
      deteriorates in cataractous lenses. Moreover, in diabetic cataractous lenses, the
      levels of very low density lipoprotein (VLDL) and LDL significantly increased. 2.
      Change in the environment surrounding the lens and peroxidative reactions. 1)
      Changes in the levels of oxidation-related substances in blood, aqueous humor,
      and vitreous body from diabetic patients: all had decreased levels of reduced
      glutathione and superoxide scavenging activity, and increased levels of lipid
      peroxide and glycated protein. This may have been due to a reduction in the anti
      oxidative potential in the environment surrounding the lens due to the enhanced
      glycation. Changes in the level of oxidation related substances in the vitreous
      body in particular, will likely have a significant impact on the lens. 2) Changes
      in lenses as the surrounding environment deteriorates. Human lenses were cultured
      for three weeks under conditions similar to those found in vivo utilizing the
      culture system that we had originally designed and constructed. When protective
      activity against peroxidation was reduced, the amount of lipid peroxide increased
      significantly. In the presence of high levels of glucose, the levels of lipid
      peroxide increased and the amount and activity of SOD decreased. 3. Effects of
      changes in the external environment on peroxidative reactions.

PMID- 8571854
TI  - [Changes in vitreous structure caused by oxygen free radicals].
AB  - Vitreous liquefaction in humans is considered to be part of the normal ocular
      aging process and is associated with vitreoretinal pathology. Because hyaluronic
      acid (HA), one of the main components of the vitreous gel structure, is degraded
      by reactive oxygen species (ROS) including oxygen free radicals, the structural
      changes in the vitreous may be caused by ROS. To investigate the effect of ROS on
      the vitreous gel structure, we treated animal vitreous with ROS, which was
      generated from various sources. Using riboflavin as a photosensitizer, calf
      vitreous was irradiated with visible light (two 15-W fluorescent lamps) and found
      to be considerably liquefied. The liquefaction resulted from HA depolymerization
      induced by ROS. Because of the small amount of riboflavin naturally present in
      the vitreous, a riboflavin-sensitized photochemical reaction may contribute to
      age-related vitreous liquefaction. Hematoporphyrin (HP), which is similar in
      chemical structure to heme in blood, was also used as a photosensitizer.
      Irradiation with HP destroyed the calf vitreous gel structure and caused
      liquefaction. A HP-sensitized photochemical reaction may contribute to vitreous
      liquefaction observed after vitreous hemorrhage. Because metal ions, including
      Fe2+ and Cu2+, can catalyze to generate ROS, liquefaction occurred when we
      treated calf vitreous with Fe2+ or Cu2+ at 4 degrees C. Adding ascorbic acid to
      the vitreous during the reaction increased the rate of liquefaction. Therefore,
      metal ion catalyzed ROS may also contribute to vitreous liquefaction, such as
      that found in an injured eye with siderosis. To investigate the relation between
      inflammatory cell mediated ROS and vitreous liquefaction, an endotoxin-induced
      uveitis model was created in the rabbit eye. Upon inflammation, the vitreous gel
      contracted and released a water-like liquid. Because superoxide dismutase can
      suppress the liquefaction, the destruction of the vitreous gel structure resulted
      from ROS generated from inflammatory cells. Although many unknown factors
      contribute to vitreous liquefaction, ROS may be the main cause of vitreous
      structure alterations. To prevent or delay the progress of vitreous liquefaction
      in the normal aging process or vitreous pathology, a new therapeutic procedure
      based on clear scientific studies is needed.

PMID- 8571855
TI  - [The role of nitric oxide in the ischemic retina].
AB  - Retinal ischemia induces a large increase in the release of glutamate, which
      exerts its toxic action by way of NMDA (N-methyl-D-aspartate) receptors onto
      amacrine cells and retinal ganglion cells. Glutamate released during ischemia and
      especially during reperfusion first stimulates non-NMDA receptors and depolarizes
      the retinal neurons. As the membrane potentials are depolarized more from the
      resting membrane potentials, the blockade of NMDA receptors induced by Mg2+ was
      released. Ca(2+)-influx through the NMDA receptors activates nitric oxide
      synthase of some amacrine cells, which produce nitric oxide (NO). NO at low
      concentrations inhibits the NMDA receptors and thereby prevents from retinal
      neuronal death. By contrast, NO at higher concentrations, interacting with oxygen
      radicals, becomes toxic and mediates glutamate-induced delayed retinal neuronal
      death.

PMID- 8571856
TI  - Local staging of prostatic carcinoma: comparison of transrectal sonography and
      endorectal MR imaging.
AB  - OBJECTIVE: We compared the results of transrectal sonography and endorectal MR
      imaging in the local staging of prostatic carcinoma. SUBJECTS AND METHODS: 56
      patients (mean age, 61.1 +/- 7.3 years) with the diagnosis of prostate cancer who
      by transrectal sonography had no evidence of gross extracapsular extension
      underwent endorectal coil MR imaging prior to radical prostatectomy. Imaging
      findings prospectively evaluated in each patient were cancer laterality,
      extracapsular extension, and seminal vesicle invasion. Twenty-one of 56 (38%)
      patients had extracapsular extension on final pathology. A total of 100 sides and
      five seminal vesicles were involved with cancer, and 27 sides (21 patients, six
      with bilateral extracapsular extension) demonstrated extracapsular extension.
      Imaging results were correlated with step-sectioned, radical prostatectomy
      pathologic data, and statistical analysis was expressed at a p = .05 level of
      significance. Retrospective readings of the images were used to construct
      receiver operating characteristic curves for the detection of extracapsular
      extension. RESULTS: For tumor laterality, transrectal sonography was compared
      with endorectal coil MR imaging for sensitivity (70% versus 97%; p < .001),
      specificity (58% versus 58%), positive predictive value (93% versus 95%) and
      negative predictive value (18% versus 70%). For extracapsular extension,
      transrectal sonography was compared with endorectal coil MR imaging for the
      entire prostate and individually for each side of the prostate. The respective
      results for sensitivity (48% versus 91%, p < .01 and 37% versus 78%, p < .005),
      specificity (71% versus 49% and 87% versus 73%), positive predictive value (50%
      versus 51% and 48% versus 48%), and negative predictive value (69% versus 90% and
      81% versus 91%). The receiver operating characteristic analysis of retrospective
      data demonstrated endorectal coil MR imaging to be superior to transrectal
      sonography in the detection of extracapsular extension. The small number of
      seminal vesicles involved by cancer (n = 5) precluded meaningful comparisons
      between the imaging techniques. CONCLUSIONS: Endorectal coil MR imaging is more
      sensitive but less specific than transrectal sonography for detecting
      extracapsular extension of carcinoma of the prostate. Both procedures have low
      positive predictive values yet similarly high negative predictive values when
      each side of the prostate is assessed independently for extracapsular extension.

PMID- 8571857
TI  - Surgical transfer of the sartorius muscle to the groin after lymphadenectomy or
      debridement: CT findings.
AB  - OBJECTIVE: We describe the CT findings of medial transfer of a sartorius muscle
      flap, which is done to protect the femoral blood vessels after radical inguinal
      lymphadenectomy for cancer or surgical debridement of infected femoral vascular
      grafts. MATERIALS AND METHODS: We reviewed the appearances and initial
      interpretations of 33 CT studies in 17 patients who underwent medial sartorius
      flap transfer after either (1) inguinal lymphadenectomy for melanoma or penile
      cancer or (2) debridement of infected groin wounds complicating vascular
      reconstruction of the femoral arteries. Muscle flap transfer was defined by the
      surgical record as either complete or incomplete. In complete sartorius muscle
      transfer, the proximal end of the muscle is dissected from the anterior superior
      iliac spine, rotated along its long axis, and sutured medially to the inguinal
      ligament. In incomplete transfer, the muscle it mobilized and stretched medially,
      and its medial border is fixed to the inguinal ligament and deep tissues.
      Clinical correlation and follow-up examinations were done for all patients, and
      CT reevaluation at intervals was done in nine patients. RESULTS: Complete
      sartorius flap transfer resulted in a mass anterolateral or anterior to the
      femoral vessels on postoperative CT scans in 20 studies; five of these masses
      were misinterpreted initially as possible recurrent metastatic lymphadenopathy,
      infection, or hematoma. Incomplete sartorius flap transfer resulted in bandlike
      stretching of the muscle over the femoral vessels in 13 studies. CONCLUSION:
      Medial transfer of the sartorius muscle causes a variable appearance of the groin
      on CT scans. The findings on CT scans after complete sartorius flap transfer
      should be distinguished from recurrent lymphadenopathy and from postoperative
      phlegmon or hematoma.

PMID- 8571858
TI  - Distinction between obstructive and nonobstructive hydronephrosis: value of
      diuresis duplex Doppler sonography.
AB  - OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of
      diuresis duplex Doppler sonography in distinguishing between obstructive and
      nonobstructive hydronephrosis by calculating the resistive indexes before and
      after administration of furosemide. SUBJECTS AND METHODS: We prospectively
      studied 48 kidneys in 26 patients with suspected chronic renal obstruction. All
      patients underwent diuretic renography and duplex Doppler sonography before and
      after administration of furosemide. According to the findings at diuretic
      renography, kidneys were classified as nonobstructed (n = 12), indeterminate (n
      =9), obstructed (n = 8), or normal (n = 19). The mean resistive index of each
      kidney and the difference between the mean resistive indexes of both kidneys were
      calculated before and after administration of 0.5 mg furosemide per kilogram of
      body weight. A receiver operating characteristic curve was generated to determine
      the discriminatory resistive index value for diagnosing obstruction. RESULTS:
      Resistive indexes were not significantly different between kidneys with
      nonobstructive dilatation and normal kidneys before and after diuresis.
      Significant differences in resistive indexes before and after diuresis were seen
      between kidneys with obstructive dilatation and kidneys with nonobstructive
      dilatation, and between normal kidneys. Kidneys with obstructive dilatation
      showed a significant increase in resistive index after administration of
      furosemide. In the indeterminate kidneys, furosemide had a heterogeneous effect
      on the resistive indexes, indicating obstructive resistive indexes in five
      kidneys and nonobstructive resistive indexes in four kidneys. Receiver operating
      characteristic analysis revealed a diuresis resistive index of 0.75, which
      resulted in an accuracy rate of 95% in diagnosing renal obstruction. CONCLUSION:
      Diuresis duplex Doppler sonography is accurate in the differentiation of
      obstructed from nonobstructed kidneys and may facilitate the distinction between
      obstructive and nonobstructive hydronephrosis, notably in kidneys classified as
      indeterminate according to diuretic renography.

PMID- 8571859
TI  - MR diagnosis of bone contusions of the knee: comparison of coronal T2-weighted
      fast spin-echo with fat saturation and fast spin-echo STIR images with
      conventional STIR images.
AB  - OBJECTIVES: Bone contusions consist of posttraumatic marrow change resulting from
      a combination of hemorrhage, edema, and microtrabecular injury and are depicted
      on MR images as geographic, nonlinear areas of abnormally increased T2 marrow
      signal intensity. Detection of bone contusions is important, not only in that
      they are frequently a sign of more serious associated injury, but in that
      isolated contusions may account for clinical symptoms and thereby obviate further
      workup. We evaluated two promising rapid imaging sequences, T2-weighted fast spin
      echo with fat saturation and fast spin-echo short inversion time (T1) inversion
      recovery (STIR) and compared their efficacy to that of conventional STIR for the
      diagnosis of bone contusions in knees. SUBJECTS AND METHODS: Fifty-one
      consecutive military, retired military, and military-dependent patients were
      prospectively entered. Imaging consisted of three experimental sequences: coronal
      T2-weighted fast spin-echo with spectroscopic fat saturation, fast spin-echo
      STIR, and STIR, as well as conventional T1, proton density, and T2. Each
      examination was interpreted by three radiologists, for a total of 153
      interpretations. Each interpretation consisted of the conventional sequences plus
      one of the three experimental sequences, blinded to the other two, specifically
      addressing menisci, ligaments, bones, and soft tissues. A positive test result
      was defined as a diagnosis of bone contusion on any one of the three independent
      interpretations of a given examination. Our gold standard was the consensus
      opinion of all three radiologists in a retrospective, unblinded evaluation of all
      imaging sequences. Sensitivity and specificity of fast spin-echo with fat
      saturation and fast spin-echo STIR were then calculated and compared with STIR.
      RESULTS: Sensitivity and specificity for bone contusion diagnosis in the three
      experimental sequences were as follows: fast spin-echo with fat saturation, 91%
      sensitivity and 86% specificity; fast spin-echo STIR, 96% sensitivity and 96%
      specificity; and conventional STIR, 83% sensitivity and 93% specificity. Our
      results showed no statistically significant difference between either of the fast
      spin-echo sequences and conventional STIR (p > .05). CONCLUSION: Because of their
      comparable accuracy and short imaging time characteristics, coronal fast spin
      echo with fat saturation and fast spin-echo STIR sequences are superior to
      conventional STIR sequences for the diagnosis of bone contusions in knees.

PMID- 8571860
TI  - The os trigonum syndrome: imaging features.
AB  - The os trigonum syndrome refers to symptoms produced by pathology of the lateral
      tubercle of the posterior talar process. Pain can be caused by disruption of the
      cartilaginous synchondrosis between the os trigonum and the lateral talar
      tubercle as a result of repetitive microtrauma and chronic inflammation.
      Additional etiologies include trigonal process fracture, flexor hallucis longus
      tenosynovitis, posterior tibiotalar impingement by bone block, and intraarticular
      loose bodies. This pictorial essay explores the role of imaging modalities in the
      diagnosis and treatment of the os trigonum syndrome, a symptom complex that may
      present difficult diagnostic problems.

PMID- 8571861
TI  - Detection of bleeding in patients with major pelvic fractures: value of contrast
      enhanced CT.
AB  - OBJECTIVE: We performed a retrospective review of trauma patients who had
      undergone both pelvic angiography and preangiographic i.v. contrast-enhanced CT
      to determine whether CT can accurately demonstrate the presence or absence of
      pelvic bleeding in patients with multisystem trauma and major pelvic fractures.
      SUBJECTS AND METHODS: We reviewed the medical records and imaging studies of all
      patients, identified through a trauma radiology database, who had undergone
      pelvic angiography and preangiographic contrast-enhanced CT during a 48-month
      period. Results of CT scans were recorded by consensus interpretation of three
      radiologists without knowledge of angiographic findings. Sites of contrast
      material extravasation seen on CT scans were noted and compared with sites of
      bleeding or vascular injury identified by selective pelvic angiography. RESULTS:
      Thirty patients with blunt trauma and pelvic fractures underwent both pelvic
      angiography and preangiographic CT studies. Findings on pelvic angiograms were
      positive at 26 sites in 19 patients and included contrast agent extravasation at
      23 sites and vessel abnormalities without extravasation at three sites.
      Preangiographic pelvic CT scans showed contrast agent extravasation at 20 sites
      in 16 patients. Three patients had no contrast agent extravasation demonstrated
      by CT but had bleeding demonstrated by angiography. CT detected bleeding in 16 of
      19 patients who had extravasation or vascular injury demonstrated by angiography,
      for a sensitivity of 84%. Results of pelvic angiography were negative in 11
      patients, and none had evidence of bleeding on preangiographic CT scans. Two
      sites of contrast agent extravasation identified in two patients by CT did not
      show bleeding at angiography, for a specificity of 85% for the detection of
      bleeding. The overall accuracy of CT for determining the presence or absence of
      bleeding was 90%. CONCLUSION: Knowledge of sites of ongoing hemorrhage is crucial
      for optimizing the sequence of diagnostic and therapeutic studies in patients
      with blunt trauma. Contrast-enhanced CT of the pelvis, which is often performed
      for hemodynamically stable trauma patients, is a noninvasive technique that is
      highly accurate in determining the presence or absence of ongoing pelvic
      hemorrhage. This information can assist in initial management decisions involving
      patients with multisystem trauma and major pelvic fractures.

PMID- 8571862
TI  - Image-guided percutaneous biopsy of musculoskeletal tumors: an algorithm for
      selection of specific biopsy techniques.
AB  - OBJECTIVE: The purpose of this study was to design and use an algorithm for
      selection of the most appropriate biopsy technique. MATERIALS AND METHODS: An
      algorithm was designed to maximize the tissue sampling and diagnostic accuracy of
      musculoskeletal tumor biopsy. We used fine-needle aspiration to sample small ( <
      3 cm) soft-tissue masses, an 18-gauge automated Biopty Gun to sample large ( > 3
      cm) soft-tissue masses, a bone-cutting core biopsy needle to sample sclerotic
      bone tumors, and a combination technique to sample lytic bone tumors with an
      intact bony shell. We reviewed the results of 46 consecutive biopsies obtained
      with this algorithm. RESULTS: The overall diagnostic accuracy was 96%, with one
      inadequate biopsy and one inaccurate biopsy. The diagnostic accuracies within
      subgroups of tumor types were: primary malignant tumors (n = 15), 93%; primary
      benign tumors (n = 9), 100%; secondary malignant tumors (n = 11), 100%; secondary
      benign tumors (n = 8), 88%; and infections (n = 3), 100%. CONCLUSION: This
      algorithm allows selection of the biopsy procedure most likely to safely provide
      adequate and accurate biopsy samples.

PMID- 8571863
TI  - Coaxial percutaneous needle biopsy of osteolytic lesions with intact cortical
      bone.

PMID- 8571864
TI  - MR findings indicative of hemosiderin in giant-cell tumor of bone: frequency,
      cause, and diagnostic significance.
AB  - OBJECTIVE: We studied the frequency, cause, and diagnostic significance of MR
      findings indicative of large amounts of hemosiderin in giant-cell tumor of bone.
      MATERIALS AND METHODS: The clinical, MR, and histologic findings in 16 patients
      with giant-cell tumors of bone were reviewed. Eight tumors occurred in uncommon
      locations or in patients who were not in the usual age range; the other eight
      were more typical. Areas of decreased MR signal intensity considered to be caused
      by hemosiderin were identified. The number and distribution of RBCs within the
      tumor were studied histologically, and the presence of hemosiderin was determined
      on histologic sections made with iron stains. RESULTS: In 10 cases in which MR
      images showed areas of low signal intensity, large amounts of hemosiderin were
      noted histologically. The low-signal-intensity areas were nodular, zonal,
      whorled, or diffuse and occupied at least one fifth of the tumor volume. On
      histologic examination, many erythrocytes were in direct contact with the tumor
      cells, and the hemosiderin was seen in both mononuclear and multinuclear tumor
      cells. CONCLUSION: Hemosiderin is commonly seen on MR images of giant-cell tumors
      of bone (63%) and is probably related to the extravasated erythrocytes in the
      tumor and the phagocytic function of the tumor cells. This MR finding supports
      the diagnosis, even in giant-cell tumors in uncommon locations or in patients who
      are not in the typical age range.

PMID- 8571865
TI  - Imaging of superficial soft-tissue infections: sonographic findings in cases of
      cellulitis and abscess.
AB  - The variation in the sonographic appearances of superficial soft-tissue
      infections probably reflects a continuous process that leads from soft-tissue
      edema, seen in cellulitis, to a fully developed abscess and that depends on the
      type of infection or the immune status of the host. We describe the sonographic
      findings seen in this process and the variable appearance of abscesses, with
      emphasis on scanning techniques that facilitate the diagnosis of liquefaction.

PMID- 8571866
TI  - Detection and differential diagnosis of pulmonary infections and tumors in
      patients with AIDS: value of chest radiography versus CT.
AB  - OBJECTIVE: The purpose of this study was to compare the sensitivity and
      specificity of chest radiography with those of CT in the detection of pulmonary
      infections and tumors in patients with AIDS. MATERIALS AND METHODS: The study was
      retrospective and included the radiographs and CT scans of 139 patients. Eighty
      nine had one proven thoracic complication, 17 had two proven thoracic
      complications, and 33 had no active intrathoracic disease at the time of the
      examinations. The radiographs and CT scans were interpreted blindly by two
      independent observers from different institutions. The observers assessed for the
      presence or absence of intrathoracic disease and recorded the most likely
      diagnosis and the degree of confidence in that diagnosis. RESULTS: The patients
      were more commonly correctly identified as having or not having intrathoracic
      disease on the basis of CT findings than on the basis of radiographic findings (
      p < .01, chi-square test). Of the 106 patients with intrathoracic complications,
      90% (191 of 212 interpretations) were correctly identified by the two observers
      on the radiograph and 96% (204 of 212 interpretations) at CT. Of 33 patients
      without intrathoracic disease, 73% (48 of 66 interpretations) were correctly
      identified at radiography and 86% (57 of 66 interpretations) at CT. Of 89
      patients with one proved thoracic complication, the observers confident in their
      first-choice diagnosis in 34% of the cases (61 of 178 interpretations) at chest
      radiography and in 47% (83 of 178 interpretations) at CT. This diagnosis was
      correct in 67% (41 of 61) of confident radiographic interpretations as compared
      with 87% (72 of 83) of interpretations at CT (p < .01, chi-square test).
      CONCLUSION: CT is superior to chest radiography in allowing identification of
      patients with and without thoracic disease and in the differential diagnosis of
      pulmonary complications of patients with AIDS. However, the improvement in
      differential diagnosis is modest. Because in most cases the radiographs and CT
      scans were obtained as part of the clinical evaluation, the study is probably
      biased toward problematic clinical cases. In the majority of patients, the chest
      radiograph provides adequate information and CT is not warranted.

PMID- 8571867
TI  - Amyloidosis of the shoulder in patients on chronic hemodialysis: sonographic
      findings.
AB  - OBJECTIVE: The purpose of this study was to determine the sonographic findings of
      amyloidosis in shoulders of patients on chronic hemodialysis. SUBJECTS AND
      METHODS: Sonograms were obtained for 19 shoulders of 11 patients on chronic
      hemodialysis with clinical findings suggestive of amyloidosis. Five patients had
      biopsy-proven amyloidosis, and one patient had positive shoulder joint fluid
      aspirate. The thicknesses of the following structures were measured: the rotator
      cuff, the subacromial-subdeltoid bursa, and the long head of the biceps tendon
      and its synovial sheath. The presence of intra- or periarticular masses or
      nodules, hyperechoic areas, bony erosions, and calcifications was specifically
      assessed. Shoulder sonograms from dialysis patients were compared with normal
      sonograms obtained for 20 asymptomatic shoulders of patients without renal
      disease. RESULTS: The mean rotator cuff thickness in the patients with
      amyloidosis was significantly greater than that in the normal group (p < .0001).
      Ten shoulders of six patients with amyloidosis but none of the control subjects
      had a rotator cuff thickness greater than 7 mm. The synovial sheath of the long
      head of the biceps tendon was thickened in 10 shoulders of patients with
      amyloidosis and in one normal shoulder. The subacromial-subdeltoid bursa was
      thickened in seven shoulders of patients with amyloidosis but not in any
      shoulders in the control group. Eight shoulder sonograms from dialysis patients
      showed intra- or periarticular nodules. CONCLUSION: Sonographic findings
      associated with amyloidosis of the shoulder include thickening of the rotator
      cuff, the synovial sheath of the long head of the biceps tendon, and the
      subacromial-subdeltoid bursa and the presence of nodules within or around the
      joint. Shoulder sonography may be useful as a noninvasive technique for the
      diagnosis of dialysis-related amyloidosis in the proper clinical setting.

PMID- 8571869
TI  - Fibromatoses of childhood: the spectrum of radiographic findings.
AB  - Fibrous tumor of childhood include several disorders with variable biologic
      behavior. In the review by Coffin and Dehner [1] of 190 soft-tissue neoplasms in
      183 children, 27% were fibroblastic or myofibroblastic in origin. Although nearly
      all fibrous lesions are benign, they may be locally aggressive. The purpose of
      this essay is to describe clinical characteristics and to illustrate radiologic
      features of commonly encountered fibrous lesions of childhood. Familiarity with
      the presentation and variable appearance may aid the radiologist in suggesting
      the diagnosis of fibromatosis.

PMID- 8571868
TI  - Renovascular hypertension resulting from nonspecific aortoarteritis in children:
      midterm results of percutaneous transluminal renal angioplasty and predictors of
      restenosis.
AB  - OBJECTIVE: Nonspecific aortoarteritis is a major cause of renovascular
      hypertension in children. Stenosis of the renal artery is usually long and begins
      at the origin of that artery. We retrospectively studied the midterm results of
      angioplasty during treatment and defined the predictors of restenosis in 40
      stenoses in 24 children. MATERIALS AND METHODS: All patients had clinically
      inactive disease and hemodynamically significant stenosis causing hypertension.
      Midterm results were analyzed by the life table method. The effect of clinical,
      angiographic, and technical factors on the restenosis rate was tested by the
      Kaplan-Meir survival method. RESULTS: Technical success was obtained without
      complications in 38 (95%) of the lesions in 22 (92%) of the patients. The
      stenosis decreased from 89 +/- 7% to 11 +/- 12%, the pressure gradient fell from
      97 +/- 27 to 10 +/- 10 mm Hg, and blood pressure decreased from 174 +/- 14/112 +/
      11 to 141 +/- 13/88 +/- 11 mm Hg (p < .001). Clinical benefit was seen in all
      patients with technically successful angioplasty. During the follow-up period (33
      +/- 22 months), restenosis was seen in eight lesions (20%). The predicted
      cumulative patency rate at 5 years was 71%. Adverse effects on the rate of
      restenosis were associated with male sex (p = .04), stenosis beginning at the
      origin of the renal artery (p = .01), and more than 20% residual stenosis after
      angioplasty (p = .02). CONCLUSION: Our results show that hypertension in children
      with renal artery stenosis caused by nonspecific aortoateritis can be safely
      treated by renal angioplasty with excellent midterm results. A long stenosis
      beginning at the origin of the artery predisposes to restenosis, but repeat
      dilatation often produces lasting benefit.

PMID- 8571870
TI  - Cystic thymic hyperplasia in a child with HIV infection: imaging findings.

PMID- 8571871
TI  - MR imaging of spinal nerve roots: techniques, enhancement patterns, and imaging
      findings.
AB  - The purpose of this report was to review the MR techniques, contrast enhancement
      patterns, and MR imaging findings for the spinal nerve roots. The phenomenon of
      contrast enhancement of the nerve roots and its relationship to disk disease and
      failed-back-surgery syndrome are discussed. The MR imaging findings for various
      inflammatory and neoplastic disorders affecting the spinal nerve roots are
      described and illustrated.

PMID- 8571872
TI  - MR imaging of the lumbar spine: enhancement of the radicular veins.
AB  - Enhancement of lumbar nerve roots in the setting of degenerative disk disease has
      been considered by several authors as evidence of a breakdown in the blood-nerve
      barrier induced by nerve root compression [1-3]. Unfortunately, correlation
      between radicular enhancement and the clinically determined level of
      radiculopathy has not been consistently shown [4, 5]. We recently proposed that
      this phenomenon represents intravascular enhancement of radicular veins that
      travel adjacent to or within the endoneurium of one or more nerve roots of the
      cauda equina [4, 5]. Our purpose in this pictorial essay is to illustrate the
      appearance of radicular vein enhancement so that this phenomenon will not be
      misinterpreted as being clinically significant in the setting of degenerative
      disk disease.

PMID- 8571873
TI  - Effect of radiation on blood volume in low-grade astrocytomas and normal brain
      tissue: quantification with dynamic susceptibility contrast MR imaging.
AB  - OBJECTIVE: The purpose of this study was to determine whether it is possible to
      measure radiation-induced changes in blood volume in low-grade astrocytomas and
      in normal brain tissue. SUBJECTS AND METHODS: The passage of a bolus of
      gadopentetate dimeglumine was monitored on a series of 55 T2*-weighted
      simultaneous dual fast low-angle shot MR images with a standard 1.5-T MR imaging
      system. Absolute blood volumes were calculated as the area under the tissue
      concentration-time curve in regions of interest and normalized to the arterial
      input function. We performed 41 examinations on 19 patients with grade II
      astrocytomas. For comparison, 13 patients were studied after whole-brain
      irradiation. RESULTS: A reduction in blood volume (mean +/- SD in milliliters per
      100 g) within the tumors from 12.2 +/- 8.7 to 6.5 +/- 5.3 after fractionated
      conformation radiotherapy was detected, although there was no consistent pattern
      in different patients. An insignificant reduction was noted in normal gray (9.2
      +/- 2.8 to 7.4 +/- 3.2) and white (4.4 +/- 1.9 to 4.1 +/- 2.3) matter outside the
      target volume. Conversely, we observed a significantly lower blood volume in gray
      (6.3 +/- 1.2) and white (3.1 +/- 1.0) matter after whole-brain radiotherapy.
      CONCLUSION: Our results show that a reduction of blood volume in astrocytomas and
      normal brain tissue after radiotherapy can be quantified by use of dynamic
      susceptibility contrast MR imaging. Thus, functional monitoring of tumor response
      and of normal tissue effects becomes possible.

PMID- 8571874
TI  - Meningitis, vasculitis, and cerebritis caused by CNS histoplasmosis: radiologic
      pathologic correlation.

PMID- 8571875
TI  - Duplex sonography of the carotid arteries in patients with isolated aortic
      stenosis: imaging findings and relation to severity of stenosis.
AB  - OBJECTIVE: The purposes of this study were to identify carotid artery duplex
      waveform abnormalities in patients with isolated aortic stenosis and to determine
      whether waveform abnormalities correlate with the severity of valvular disease.
      MATERIALS AND METHODS: Twenty-four patients with various degrees of aortic
      stenosis diagnosed by echocardiography and/or cardiac catheterization had
      preoperative carotid artery duplex sonograms that were retrospectively reviewed
      for acceleration time, peak velocity, waveform contour, upstroke delay, and
      presence of a dicrotic notch and a second systolic peak. Data were collected for
      the right and left internal, external, and common carotid arteries separately.
      These findings were correlated with aortic valve area and compared with data for
      a control group of 11 age-matched patients with normal echocardiographic
      findings. Two additional patients with isolated aortic stenosis diagnosed by
      echocardiography and/or cardiac catheterization were prospectively evaluated in a
      similar fashion, with acceleration time being calculated directly from the
      sonography unit. RESULTS: Unlike the patients with mild or moderate stenosis, the
      patients with critical or severe stenosis had a mean acceleration time that was
      significantly longer than that in the control subjects (p = .008-.0001). Peak
      velocities were decreased in all cases of aortic stenosis regardless of severity
      only in the common carotid arteries. All 13 patients with critical aortic
      stenosis had delayed upstrokes and rounded waveforms in the common, internal, and
      external carotid arteries. Twenty percent (one of five) of the patients with
      severe stenosis and 17% (one of six) of the patients with moderate or mild
      stenosis also had these characteristics. The two prospectively evaluated
      patients, who had critical and severe aortic stenoses, had similar findings. None
      of the control subjects showed these abnormalities. The presence or absence of a
      second systolic peak or a dicrotic notch was not different between patients with
      aortic stenosis and control subjects. CONCLUSION: Increased acceleration time,
      decreased peak velocity, delayed upstroke, and rounded waveform are
      characteristic abnormalities found in duplex sonographic studies of the carotid
      arteries in patients with aortic stenosis. The degree of each of these
      abnormalities correlates with the valve area. Patients with critical or severe
      aortic stenosis had findings significantly different from those in the control
      group. Patients with mild or moderate disease showed few or no sonographic
      abnormalities.

PMID- 8571876
TI  - Penetrating ulcer of the descending aorta mimicking a traumatic aortic
      laceration.

PMID- 8571877
TI  - Color Doppler sonography in Graves' disease: value in assessing activity of
      disease and predicting outcome.
AB  - OBJECTIVE: The aims of the study were to establish the usefulness of color
      Doppler sonography in assessing changes in thyroid blood flow during the course
      of Graves' disease and to investigate which of several variables (thyroid volume,
      number of intraparenchymal vessels, and blood flow in the thyroid artery) were
      best related to thyroid hyperfunction and therefore could be used to evaluate the
      course of the disease. SUBJECTS AND METHODS: Fifty-six patients with Graves'
      disease were selected and divided on the basis of clinical and laboratory data
      into four groups: patients untreated at first diagnosis, patients undergoing
      antithyroid drug treatment, patients in remission after withdrawal of therapy,
      and patients having a relapse of hyperthyroidism. Ten healthy subjects served as
      controls. RESULTS: Patients with active hyperthyroidism (at first diagnosis,
      during treatment, or at relapse) had a significantly enlarged thyroid (p = .005);
      intrathyroid vascularization, evaluated as number of vessels per square
      centimeter (p < .0001); and blood flow in the thyroid artery (p < .0001) compared
      with control subjects and with patients in remission after withdrawal of therapy.
      During treatment, sonographic values were slightly lower but not significantly
      different from those registered in patients at the onset of hyperthyroidism,
      indicating that normalization of vascularity does not parallel the drug-induced
      decrease of hormonal synthesis. Among 21 patients in remission, the nine patients
      who had a relapse shortly after the examination had a higher number of vessels
      per square centimeter (2.18 +/- 0.34 versus 1.03 +/- 0.16, p = .03) and higher
      flow in the thyroid artery (80.3 +/- 19.1 versus 10.6 +/- 2.3 ml/min, p = .01)
      than did the other 12 patients who remained in stable remission, despite normal
      hormonal levels in both groups. CONCLUSION: Our results suggest that color
      Doppler sonography can be used to assess activity of Graves' disease and to
      predict the outcome of the disease after withdrawal of medical therapy.

PMID- 8571878
TI  - Is measuring renal function necessary in all patients prior to administering IV
      contrast?

PMID- 8571879
TI  - Infection with Helicobacter pylori.

PMID- 8571880
TI  - Mediastinal tuberculous lymphadenitis: MR imaging appearance with
      clinicopathologic correlation.
AB  - OBJECTIVE: The purpose of our study was to determine the MR imaging appearance of
      mediastinal tuberculous lymphadenitis and to compare these findings with clinical
      and pathologic findings. MATERIALS AND METHODS: MR images of 23 consecutive
      patients with mediastinal tuberculous lymphadenitis were retrospectively analyzed
      with regard to homogeneity, signal intensity, and enhancement of diseased nodes
      after injection of contrast material (n = 19), and the imaging findings were
      grouped by patterns and correlated with clinical signs or symptoms and with
      pathologic (n = 9) findings. RESULTS: Three imaging patterns of mediastinal
      tuberculous lymphadenitis (113 nodes) were seen of MR images. In six patients,
      nodes (type 1, n = 25) were relatively homogeneous and hyperintense to muscle on
      both T1- and T2-weighted images and enhanced homogeneously after injection of
      contrast material. The patients had mild (n = 2) or no (n = 4) constitutional
      symptoms. The nodes corresponded pathologically to tuberculous granulomas without
      or with minimal necrosis. In 14 patients, nodes (type 2, n = 71) were
      inhomogeneous with a strong peripheral enhancement after injection of contrast
      material. Enhancing areas were of intermediate intensity on T1-weighted images
      and hypointense on T2-weighted images, and corresponded pathologically to
      peripheral granulation tissue within the nodes. Unenhanced areas were relatively
      hypointense on T1-weighted images and markedly hyperintense on T2-weighted
      images, and corresponded pathologically to central caseation or liquefaction
      necrosis within the nodes. All but one patient with type 2 nodes had moderate to
      severe clinical signs and symptoms. In the remaining three patients, nodes (type
      3, n = 17) were homogeneously hypointense on both T1- and T2-weighted images and
      did not enhance after injection of contrast material. No patient with type 3
      nodes had clinical signs or symptoms. The nodes corresponded pathologically to
      fibrocalcified nodes. CONCLUSION: The most common MR imaging appearance of
      mediastinal tuberculous lymphadenitis was as inhomogeneous nodes with marked
      hyperintensity on T2-weighted images and peripheral enhancement after injection
      of contrast material. This typical MR imaging appearance was mostly seen in
      severely symptomatic patients and was due to caseation necrosis of the
      tuberculous nodes.

PMID- 8571881
TI  - When should radiologists intervene in management of pancreatic pseudocysts and
      other complications of acute pancreatitis?

PMID- 8571882
TI  - Carotid calcification seen as an incidental finding on plain films.

PMID- 8571883
TI  - What are the indications, if any, for conventional myelography?

PMID- 8571884
TI  - Discovered by chance?

PMID- 8571885
TI  - Making slides from radiographs.

PMID- 8571886
TI  - Hypoechoic fat: another location.

PMID- 8571887
TI  - Endobronchial lymphoma.

PMID- 8571888
TI  - Doppler velocity criteria for transjugular intrahepatic portosystemic shunt
      (TIPS) stenosis.

PMID- 8571889
TI  - Caroli's disease: evaluation with MR cholangiography.

PMID- 8571890
TI  - Re: Color Doppler sonography of hepatic tumors with a galactose-based contrast
      agent.

PMID- 8571891
TI  - Radiation-induced rhabdomyosarcoma.

PMID- 8571892
TI  - Re: Imaging of acute injuries of the cervical spine: value of plain radiography,
      CT, and MR imaging.

PMID- 8571893
TI  - Intracranial calcification in patient with insulin-dependent diabetes mellitus.

PMID- 8571894
TI  - Aberrant internal carotid artery on midline cervical spine MR image.

PMID- 8571895
TI  - Re: Atheromatous macroembolism after balloon angioplasty of the superficial
      femoral artery.

PMID- 8571896
TI  - Delayed closure of a postcatheterization pseudoaneurysm of the brachial artery by
      sonographically guided digital compression.

PMID- 8571897
TI  - Posterior mediastinal chordoma: MR imaging findings.

PMID- 8571898
TI  - Mammographic appearance of cancer in the opposite breast: comparison with the
      first cancer.
AB  - OBJECTIVE: Patients who have had cancer in one breast are at high risk for cancer
      in the contralateral breast. These bilateral cancers may be synchronous or
      metachronous. If the manifestations on mammography were similar in both breasts,
      an aggressive search for the mammographic findings of the first breast cancer
      might lead to early detection of the contralateral cancer. The purpose of this
      study was to evaluate mammograms for patients with bilateral cancers to determine
      whether the mammographic appearance of the contralateral cancer is likely to be
      the same as that of the first cancer. MATERIALS AND METHODS: We retrospectively
      reviewed the pathologic and mammographic records of 69 patients with surgically
      proven bilateral primary breast cancer. Thirty four of 69 (49%) had synchronous
      cancer, and 35 (51%) had metachronous cancer. Mammographic appearances were
      classified as microcalcifications, spiculated mass, nonspiculated mass (whether
      circumscribed or poorly defined), asymmetric or developing density, architectural
      distortion, and normal. Multiple findings were subclassified as major and minor
      findings. All findings were compared between both breast cancers, and statistical
      significance was determined by the two-sample Z test. RESULTS: Forty six (67%) of
      69 patients had different major mammographic findings in the contralateral
      cancer. Of 30 patients whose first cancers had microcalcifications, 20 (67%) had
      microcalcifications in the contralateral cancer. Of 39 patients whose first
      cancers lacked microcalcifications, 17 (44%) had microcalcifications in the
      contralateral cancer. This difference was statistically significant (p = .02). Of
      26 patients whose first cancers had spiculated masses, 9 (35%) had a
      contralateral spiculated mass. Of 43 patients whose first cancers lacked
      spiculated masses, 12 (28%) had a contralateral spiculated mass. This difference
      was not statistically significant (p = .22). CONCLUSION: Our results show that
      contralateral tumors usually have major mammographic findings different from
      those of the first cancer, and the mammographic signs of the first cancer do not
      indicate the most likely appearance of cancer in the contralateral breast.
      Evaluation of a contralateral mammogram should be performed without regard for
      the mammographic findings for the first cancer.

PMID- 8571899
TI  - Changing of the guard at the American Journal of Roentgenology: the Robert Berk
      era revisited.
AB  - As determined by the Executive council of the American Roentgen Ray Society, the
      editorship of the American Journal of Roentgenology (AJR) is a time-limited
      position. This policy allows for the perpetual influx of new ideas and ensures
      continued dynamism in the leadership of the Journal. The AJR now has a new editor
      in chief, Lee F. Rogers, M.D., as well as a new office staff and a new home for
      the editorial office, Winston-Salem, NC. As we look with anticipation to the
      future of the Journal under the guidance of Lee Rogers, the time is appropriate
      to reflect on the legacy of journalistic excellence and innovation that Robert N.
      Berk has left us.

PMID- 8571900
TI  - The sternalis muscle: an unusual normal finding seen on mammography.
AB  - OBJECTIVE: We studied the appearance of the sternalis muscle on mammography and
      on CT and MR imaging. To our knowledge, this is the first description of this
      normal anatomic variant. An approach is provided that permits differentiation of
      the sternalis from significant pathology. SUBJECTS AND METHODS: Between January
      1992 and December 1994, four women of an estimated 32,000 who had mammograms at
      the Massachusetts General Hospital had an unusual, irregular structure visible
      medially on the craniocaudal projection that posed a diagnostic dilemma. The
      records and imaging studies of these women and two others from the Deaconess
      Hospital breast imaging program were reviewed to determine the etiology of the
      findings seen by mammography and to establish a diagnostic approach. RESULTS:
      Surgery in one patient and cross-sectional imaging in the other five established
      that the structure was the sternalis muscle. Although it may be bilateral, the
      sternalis muscle was visible only unilaterally on the mammograms of these six
      women. The appearance of the muscle ranged from an irregularly rounded density at
      the sternal edge of the film to flame-shaped and almost completely surrounded by
      fat. CT and MR imaging are diagnostic when they show the longitudinal extent of
      the muscle, which lies anterior to the medial margin of the pectoralis major
      muscle. CONCLUSION: The sternalis muscle is an unusual variant of the chest wall
      musculature. It may be visible as a rounded or irregular density on the
      craniocaudal mammogram along the sternal edge of the film. With improved
      mammographic positioning it will be seen more frequently. The muscle has a
      variety of appearances that should be familiar to the radiologist to avoid
      confusion with a malignant lesion. The etiology can be confirmed and cancer
      excluded by CT or MR imaging.

PMID- 8571901
TI  - Preoperative staging of cancer of the pancreas: value of MR angiography versus
      conventional angiography in detecting portal venous invasion.
AB  - OBJECTIVE: The purpose of this study was to compare contrast-enhanced MR
      angiography with conventional catheter angiography for detecting portal venous
      invasion in the preoperative staging of pancreatic cancer, using the surgical
      confirmation of vascular involvement as the standard of truth. SUBJECTS AND
      METHODS: MR and conventional angiography were performed in 20 patients with
      pancreatic carcinoma, with surgical confirmation in all cases. MR angiography was
      performed at 1.5 T, with coronal (2.9 mm) and axial (6.0 mm) contrast-enhanced
      breath-hold two-dimensional time-of-flight imaging. Data from each imaging
      technique were collected prospectively and analyzed in a blinded fashion by
      expert vascular radiologists. Vascular involvement in each patient and in each
      vessel (main portal vein, confluence, splenic vein, and superior mesenteric vein)
      determined whether the tumor was resectable (normal, abutment) or nonresectable
      (encased, occluded). Surgical confirmation of the vascular involvement of the
      portal venous structures was used as the standard of truth in all patients.
      RESULTS: Among the 20 patients, 11 tumors were surgically resectable and seven
      were nonresectable with performance of a palliative bypass. MR angiography and
      conventional angiography had an overall concordance in 65% of patients (13/20;
      seven resectable, four nonresectable, two false-negatives) on the basis of the
      vascular status in each patient of the portal venous structures and in 84%
      (47/56) of the individual vessels surgically confirmed. MR angiography correctly
      identified 11 of 11 resectable patients and five of nine nonresectable patients,
      with four false-negative cases. Conventional angiography correctly identified
      seven of 11 resectable patients and six of nine nonresectable patients, with
      three false-negative cases and four false-positive cases. CONCLUSION: The lack of
      false-positives by MR angiography suggests that MR imaging may provide a
      noninvasive screen for nonresectability on the basis of vascular involvement,
      with no patients with potentially resectable tumors being denied surgery by MR
      angiography in this cohort. However, the presence of false-negatives using MR
      angiography indicates the procedure would still not fully eliminate unnecessary
      laparotomies.

PMID- 8571902
TI  - Endoscopic sonography of the upper gastrointestinal tract and pancreas.
AB  - Endoscopic sonography is a new approach to visualizing upper gastrointestinal
      lesions. The sonographic device, which incorporates a sonographic transducer
      mounted on a standard fiberoptic endoscope, makes it possible to obtain high
      resolution images of mucosal and mural lesions of the gastrointestinal tract, as
      well as of adjacent masses. This technique has substantially improved
      preoperative staging of esophageal and gastric cancers. In addition, high
      resolution sonographs of the pancreas can be obtained without degradation by
      overlying bowel gas, making identification of small, previously occult lesions of
      the pancreatic head possible. We have used endoscopic sonography in staging
      esophageal, gastric, and pancreatic cancers in more than 200 patients. This essay
      illustrates our experience with this new technique.

PMID- 8571903
TI  - Extrapancreatic gastrinoma localization: value of arterial-phase helical CT with
      water as an oral contrast agent.

PMID- 8571904
TI  - Pancreaticobronchial fistula diagnosed by combined ERP and CT.

PMID- 8571905
TI  - Endorectal color Doppler imaging of primary and recurrent rectal wall tumors:
      preliminary experience.
AB  - OBJECTIVE: The purpose of our study was to assess whether color Doppler imaging
      is a useful adjunct to endorectal sonography in evaluating rectal wall neoplasms
      and in distinguishing recurrent or residual tumor from postoperative changes.
      MATERIALS AND METHODS: Thirty-two patients underwent endorectal sonography with
      color Doppler imaging for one of two indications: evaluation and staging of a
      suspected primary rectal wall cancer, or distinguishing tumor recurrence from
      postoperative scarring in patients with previously resected lesions. Rectal wall
      lesions were evaluated for hypervascularity, and their corresponding flow
      patterns were graded from 0 to 4. Local tumor staging with endorectal sonography
      and color Doppler imaging was performed before the results of pathological
      staging were available. RESULTS: Ninety-five percent of patients with malignant
      rectal wall tumors demonstrated hypervascularity during color Doppler imaging. In
      61% of patients with rectal cancers, prominent perirectal vessels were identified
      supplying the tumor and were never identified in patients with benign lesions.
      Endorectal sonography alone correctly identified perirectal fat invasion with a
      100% sensitivity and an 83% specificity. Color Doppler imaging during endorectal
      sonography correctly identified perirectal fat invasion with a sensitivity of 91%
      and a specificity of 83%. Of the 8 patients with previously resected lesions
      (five adenomas and three cancers), two patients had recurrent tumor, and both of
      these demonstrated grade 3 abnormality. Six patients with biopsy-proven fibrosis
      only had grades of 0 or 1. CONCLUSIONS: Both benign and malignant rectal wall
      tumors demonstrate abnormal intratumoral hypervascularity when seen with color
      Doppler imaging. Advanced rectal cancers (T3 or greater) are also associated with
      abnormal perirectal vascularity. Color Doppler imaging during endorectal
      sonography does not appear to improve discrimination of benign from T2 (or less)
      rectal wall cancers, nor does it appear to improve the ability to locally stage
      rectal wall cancers during endorectal sonography. However, endorectal sonography
      with color Doppler imaging may add significant information in distinguishing
      recurrent tumor from postsurgical scarring.

PMID- 8571906
TI  - Is constipation a disorder of defecation or impaired motility?: distinction based
      on defecography and colonic transit studies.
AB  - OBJECTIVE: The purpose of this study was to determine whether constipation is a
      disorder of defecation or of impaired motility by using defecography and transit
      studies. MATERIALS AND METHODS: Thirty-five patients (34 women, one man) with
      severe constipation underwent defecography and colonic transit studies in a 2
      month period. Transit studies included the use of orally administered radiopaque
      markers and plain abdominal radiographs obtained up to 4 days later.
      Fluoroscopically guided defecography was performed with barium paste introduced
      into the rectum. RESULTS: Normal colonic transit time was observed in seven (20%)
      of the 35 patients. Abnormal findings included colonic inertia in six (17%)
      patients, hindgut dysfunction in 10 (29%) patients, and outlet obstruction in 12
      (34%) patients. Rectocele, enterocele, descending perineum syndrome, and
      dyskinetic puborectalis were found equally in both groups of patients. Rectal
      prolapse was more commonly found in patients with hindgut dysfunction and outlet
      obstruction (p < .05). CONCLUSION: Surgical or medical management of severely
      constipated patients relies on objectively identifying the underlying
      pathophysiology. Our findings suggest that constipation is often a disorder of
      defecation rather than an impairment of colonic motility.

PMID- 8571907
TI  - Detection of intestinal ischemia in patients with acute small-bowel obstruction
      due to adhesions or hernia: efficacy of CT.
AB  - OBJECTIVE: The purpose of this study was to determine whether CT can be used to
      diagnose ischemia of the small intestine in patients with small-bowel obstruction
      due to adhesions or hernia. SUBJECTS AND METHODS: During a 12-month period, 60
      patients underwent surgery for complete or high-grade small-bowel obstruction due
      to adhesions or hernia, and 29 (48%) had evidence of associated intestinal
      ischemia. All of these patients had been preoperatively diagnosed by CT as having
      high-grade small-bowel obstruction. At the same time, a prospective determination
      was made based on the CT as to whether there was any associated intestinal
      ischemia. All CT scans were performed within 24 hours of the operation. A CT
      diagnosis of ischemia was based on the presence of two or more of the following
      signs: bowel-wall thickening, high attenuation of the bowel wall on unenhanced CT
      scans, mesenteric edema or fluid, asymmetric bowel-wall enhancement on i.v.
      contrast-enhanced CT scans, pneumatosis, or portal venous gas. Results of the CT
      examination and surgical findings were then compared. Further evaluation was done
      with a retrospective multivariate discriminant analysis. RESULTS: Ischemia was
      prospectively diagnosed on the basis of CT findings in 41 (68%) of the 60
      patients. There were no false-negative CT diagnoses (sensitivity, 100%); however,
      there were 12 CT diagnoses that were false-positive (specificity, 61%). The
      multivariate analysis corroborated the prospective results by showing high
      sensitivity (90%) and diminished specificity (50-64%). Bowel-wall thickening and
      high attenuation of the bowel wall were the most important signs of ischemia on
      unenhanced CT scans, whereas abnormal bowel-wall enhancement and mesenteric fluid
      correlated best on enhanced CT examinations. CONCLUSIONS: CT is a sensitive but
      not completely specific preoperative indicator of intestinal ischemia in patients
      with small-bowel obstruction due to hernias or adhesions.

PMID- 8571908
TI  - Endothelial cell function: biologic and physiologic functions in health and
      disease.
AB  - Endothelial cells (EC) form a monolayer with a strategic role in the control of
      many physiologic and biologic pathways. Although the endothelium initially was
      thought to be an inert and passive barrier of the vasculature, the diverse
      functions of EC have been better defined in the past decade. EC play an important
      role in the control of coagulation, vasomotor tone, growth of vascular smooth
      muscle cells, white cell trafficking, ischemic and reperfusion injuries, and the
      development of arteriosclerosis. Owing to their location in the arterial tree, EC
      also are considered a potential target for gene therapy. The introduction of
      foreign DNA into EC by in vitro transfection with viral vectors has produced
      encouraging results when using genes that encode for proteins such as insulin and
      urokinase. The seeding of EC onto vascular grafts appears to convey the
      thromboresistant properties of saphenous vein to an artificial surface. This
      review focuses on the important biologic and physiologic functions of EC in
      health and disease.

PMID- 8571909
TI  - Embryonal rhabdomyosarcoma of the prostate.

PMID- 8571911
TI  - Palliative treatment of obstructing esophageal cancer with nitinol stents: value,
      safety, and long-term results.
AB  - OBJECTIVE: The purpose of our study was to evaluate the effectiveness of nitinol
      stents for palliation of dysphagia due obstructing esophageal cancer, safety of
      stent placement, and long-term results. SUBJECTS AND METHODS: Self-expanding
      uncoated nitinol stents were inserted either radiologically (14 patients) or
      endoscopically (12 patients) on an outpatient basis in 26 consecutive patients
      with dysphagia grade 3 or 4 caused by incurable malignant obstructions in the
      middle or distal third of the esophagus (n = 22) or at esophagojejunal
      anastomoses (n = 4). No esophagotracheal fistulas were seen in any patient. In 22
      patients prior treatments had failed. Following insertion, the stent lumen was
      dilated to the maximum diameter. Finally, esophagography or esophagoscopy was
      done to confirm the position of the stent and patency of the esophageal lumen.
      Twenty-four hours after the procedure, esophageal function was investigated by a
      barium swallow. Patients were encouraged to ingest solid food thereafter.
      Improvement in dysphagia was evaluated 1 week after stent placement and during
      monthly interviews. Complications were defined as major (aspiration, bleeding,
      stent misplacement or dislocation, perforation) or minor (reflux esophagitis,
      chest pain, pharyngeal discomfort). Tumor ingrowth or overgrowth was considered a
      treatment failure. Twenty-three patients (88%) were followed until death: three
      patients (12%) were followed for a mean of 14 months. RESULTS: Exact positioning
      of the stent and dilation to its maximum diameter were technically feasible in
      all patients. No stents were placed in the stomach. Patency of the esophageal
      lumen was successfully restored in 25 patients. In one patient a broken strut of
      the stent after dilation caused a partial obstruction, which was detected
      endoscopically. Two patients had recurrent dysphagia due to tumor ingrowth or
      overgrowth, one after 1 month and the other after 3 months. In these patients an
      additional overlapping stent was successfully placed. No procedure-related
      mortalities or major complications occurred. The mean dysphagia grade of 3.5 was
      improved to a mean grade of 0.6 after stent placement. All patients could take
      liquids within the first 24 hr. Fifteen patients improved to dysphagia grade 0,
      seven patients to grade 1, and four patients to grade 2 within 1 week after the
      procedure. Twenty-three patients (88%) died during the follow-up period (mean
      survival, 5 months) as a result of their disease. Latest evaluation of the mean
      dysphagia grade was 0.7. Three patients (12%) are still alive (mean survival, 14
      months) with a dysphagia grade 1 in one patient and grade 0 in two. CONCLUSION:
      Implantation of nitinol stents proved to be an effective and safe method of
      palliating severe dysphagia in patients with obstructing esophageal cancer. The
      improvement in dysphagia was impressive and long lasting. Placement of the stents
      was feasible without major procedure-related complications.

PMID- 8571910
TI  - MR contrast material for vascular enhancement: value of superparamagnetic iron
      oxide.
AB  - OBJECTIVE: The purpose of this study were to quantify abdominal vascular
      enhancement and to prove the feasibility of iron oxide-enhanced MR angiography in
      humans using three doses of superparamagnetic iron oxide agent AMI 227. SUBJECTS
      AND METHODS: Sixteen patients randomly received either 0.8, 1.1, or 1.7 mg Fe/kg
      of ultrasmall superparamagnetic iron oxide agent AMI 227. T1-weighted breath-hold
      gradient-echo images were obtained before and 45 min after i.v. administration of
      AMI 227. Signal intensity was measured in the aorta, the inferior vena cava, the
      portal vein, and muscle on unenhanced and contrast-enhanced images. Signal-to
      noise ratios and enhancement [(SNR after contrast-SNR before contrast) / SNR
      before contrast] were calculated. Vessels were visually graded before and after
      administration of AMI 227. RESULTS: All vessels showed statistically significant
      enhancement 45 min. after administration of AMI 227 by both qualitative and
      quantitative measures (p < .001). There was no significant increase in noise or
      signal intensity of muscle after contrast material was administered. The amount
      of enhancement was not statistically significantly different among the three
      doses. CONCLUSIONS: AMI 227, which is currently in phase III clinical trials,
      demonstrates significant vascular enhancement and may prove useful as an MR
      angiographic contrast agent.

PMID- 8571912
TI  - Helicobacter pylori and gastric MALT lymphoma.

PMID- 8571913
TI  - Vascular ectasia of the gastric antrum: angiographic findings.

PMID- 8571914
TI  - Portal-phase contrast-enhanced helical CT for the detection of malignant hepatic
      tumors: sensitivity based on comparison with intraoperative and pathologic
      findings.
AB  - OBJECTIVE: The purpose of this study was to determine the sensitivity of portal
      phase IV contrast-enhanced helical CT in detecting malignant hepatic tumors using
      a lesion-by-lesion comparison with surgical and pathologic findings. MATERIALS
      AND METHODS: Preoperative portal-phase contrast-enhanced helical CT studies in 21
      patients (13 men, eight women) with malignant neoplasms of the liver (12 patients
      with primary hepatic tumors, nine patients with metastases) were reviewed
      retrospectively by three radiologists with the knowledge that hepatic
      malignancies were present in each case. Helical CT findings were compared with
      intraoperative findings by palpation (21 patients), sonography (15 patients), and
      the results of pathologic examination of resected specimens (10 patients) in a
      lesion-by-lesion manner. Sixty-four malignant nodules were identified in resected
      specimens or at surgery by palpation or intraoperative sonography. For each
      nodule identified by surgical or pathologic means, CT findings were reviewed for
      the presence of a lesion of similar size and location. RESULTS: The readers
      identified 52 of 64 nodules on helical CT scans for an overall sensitivity of
      81%. Sixteen of 21 primary tumors (76%) and 36 of 43 metastatic tumors (84%) were
      identified on CT scans. The sensitivity was 91% for nodules greater than 1 cm (42
      of 46) and 56% for nodules 1 cm or less (10 of 18). False-positive findings
      occurred in 4% of lesions seen on helical CT scans. CONCLUSION: Our results show
      that portal-phase contrast-enhanced helical CT is extremely sensitive (91%) for
      detecting malignant hepatic tumors greater than 1 cm, is relatively insensitive
      (56%) for tumors less than 1 cm, and has a low false-positive rate. These results
      compare favorably with published results for CT during arterial portography, the
      current gold standard for liver tumor detection, suggesting that portal-phase IV
      contrast-enhanced helical CT is an excellent noninvasive preoperative study prior
      to hepatic resection or cryosurgery.

PMID- 8571916
TI  - White Paper Report on U.S. Industry Safety and Health Practices.

PMID- 8571915
TI  - Diagnosis of acute flank pain: value of unenhanced helical CT.
AB  - OBJECTIVES: The purpose of our study was to determine the value of unenhanced CT
      in the diagnosis of acute flank pain. We determined the accuracy of unenhanced Ct
      for stone detection as well as the detection of abnormalities unrelated to stone
      disease. MATERIALS AND METHODS: During an 18-month interval, 292 patients with
      acute flank pain were imaged with unenhanced CT. Confirmation of the CT diagnosis
      was obtained for 210 patients: One hundred patients were proved to have ureteral
      stones based on other imaging studies (58 patients), lithotripsy (seven
      patients), ureteroscopic stone extraction (five patients), and stone recovery (30
      patients). One hundred ten patients were proved not to have ureteral stones based
      on other imaging studies (24 patients), failure to recover a stone (56 patients),
      or a confirmed diagnosis unrelated to stone disease (30 patients). This latter
      group of 30 patients included diagnoses of adnexal masses (eight patients),
      appendicitis (five patients), diverticulitis (four patients), and common bile
      duct stones (three patients), as well as other diagnoses. RESULTS: Unenhanced CT
      findings were falsely negative for stone disease in three patients and falsely
      positive for stone disease in four patients. These data yield a sensitivity of
      97%, a specificity of 96%, and an accuracy of 97% for diagnosing ureteral stone
      disease. Of 31 patients with a CT abnormality unrelated to stone disease, there
      was one false-negative diagnosis of acute appendicitis. CONCLUSION: Unenhanced CT
      is a valuable technique for examining patients with acute flank pain in whom a
      clinical diagnosis is uncertain. It can accurately determine the presence or
      absence of ureteral stones as well as extraurinary causes of acute flank pain. In
      most cases, other imaging studies are not required.

PMID- 8571917
TI  - Analysis of fluorescence spectra from Chinese herbal medicine for male
      infertility.
AB  - To clarify the contribution of Chinese herbal medicine to the treatment of male
      infertility, fluorescence spectra from Chinese herbal drugs at 500-700 nm with
      488 nm excitation were investigated. The fluorescence spectra patterns from
      Hachimi-jio-gan, Gosha-jinki-gan and Hochuekki-to were similar to those from
      semen, seminal plasma and spermatozoa. Our previous report revealed that the
      concentration of spermatozoa correlated with the intensity of the emission peaks
      from spermatozoa, while sperm motility correlated with the emission peaks from
      spermatozoa and semen plasma. Thus, it was suggested that the components of these
      fluorescence productions in Chinese herbal medicine may contribute to clinical
      effects for male infertility.

PMID- 8571918
TI  - The effect of unkei-to on pituitary gonadotropin secretion and ovulation in
      anovulatory cycles of young women.
AB  - Unkei-to (TJ-106) induced significant increases of plasma follicle stimulating
      hormone level in the first grade (P < 0.05), second grade amenorrhea without
      weight loss (P < 0.05), and weight loss related to second grade amenorrhea (P <
      0.01) in eight weeks of treatment, respectively. Plasma estradiol level
      significantly increased 1.8 times in 4 week treatment with Unkei-to in first
      grade amenorrhea (P < 0.01). In second grade amenorrhea without weight loss and
      weight loss related second grade amenorrhea, plasma estradiol level significantly
      increased 2.9 times (P < 0.01) and 1.7 times (P < 0.05) in 8 weeks treatment,
      respectively. On the other hand, the patterns of pulsatile secretion of follicle
      stimulating hormone and luteinizing hormone remarkably improved by the treatment
      with Unkei-to. In the patients with second grade amenorrhea, follicles
      stimulating hormone and luteinizing hormone pulses appeared in 3 out of 13
      (23.1%) and 6 out of 13 (46.2%) with the treatment of Unkei-to, respectively in
      85% of whom no pulses has been observed before the treatment. Ovulation occurred
      in 62.2% (23/37), 26.6% (4/15), and 21.7% (5/23) of the patients with first
      grade, second grade amenorrhea without weight loss, and weight loss related
      second grade amenorrhea by the treatment with Unkei-to, respectively. These
      results indicate that Unkei-to is effective on improvement of gonadotropin
      pulsatile secretion in the treatment of anovulatory women. This suggests that
      Unkei-to may enhance the pituitary response to Gn-RH or improvement of the
      pulsatile secretion of Gn-RH, inducing normalization of diencephalon-pituitary
      ovarian endocrine system in the anovulatory patients.

PMID- 8571919
TI  - Tokishakuyakusan effect on DNA polymerase alpha activity in relationship to DNA
      synthesis before and/or after the LH/FSH surge in rats.
AB  - DNA polymerase alpha activity in ovaries of mature cycling rats during the normal
      estrous cycle changed in a cyclic manner with a peak at 1800 h in proestrus.
      Tokishakuyakusan (TS) in vivo did not affect the changes in DNA polymerase alpha
      and beta activities during the estrous cycle. LH and FSH at 1000 or 1700 h in
      proestrus increased DNA polymerase alpha activity, but the DNA polymerase alpha
      activity induced by LH or FSH was not significantly affected by the addition of
      TS. DNA polymerase beta activity did not change with LH, FSH or TS. In PMS
      treated or -untreated immature rats, TS enhanced ovarian DNA polymerase alpha
      activity but had no significant effect on LH or FSH action. In ovaries, incubated
      in vitro, in untreated mature or immature rats, TS enhanced ovarian DNA
      polymerase alpha activity but had no significant effect on LH or FSH action.
      These results suggest that TS stimulates ovarian DNA polymerase alpha activity in
      relationship to DNA synthesis and does not affect the effect of LH or FSH on the
      activity by preovulatory follicle before and/or after the LH/FSH surge.

PMID- 8571920
TI  - Protective and therapeutic effects of Curcuma xanthorrhiza on hepatotoxin-induced
      liver damage.
AB  - Curcuma xanthorrhiza Roxb. (Zingiberaceae family, commonly known as temu lawak or
      Javanese turmeric in Indonesia), which is found both wild and cultivated in
      Indonesia, has been traditionally used for medicinal purposes. C. xanthorrhiza is
      also used as a tonic in Indonesia. The aim of the present study is to clarify
      whether C. xanthorrhiza treatment may prevent acute liver damage induced by
      acetaminophen and carbon tetrachloride in mice. The results clearly indicated
      that extract of C. xanthorrhiza could reduce significantly the acute elevation of
      serum transaminases levels induced by the two kinds of hepatotoxins, and
      alleviated the degree of liver damage at 24 hours after the intraperitoneal
      administration of two hepatotoxins. It may be concluded that C. xanthorrhiza can
      protect the liver from various hepatotoxins, hence C. xanthorrhiza could be
      useful in the treatment of liver injuries and has promise as a kind of broad
      spectrum hepatoprotective agent.

PMID- 8571921
TI  - Therapeutic effect of chai-ling-tang (sairei-to) on the steroid-dependent
      nephrotic syndrome in children.
AB  - 37 children with steroid-dependent nephrotic syndrome (SDNS) were administered
      with Chai-Ling-Tang (Sairei-to) under corticosteroid. After treatment with Chai
      Ling-Tang, relapse was markedly improved, time for negative conversion of
      proteinuria shortened, prednisone dosage significantly reduced, and side effects
      eased. 32 children with SDNS treated with prednisone and cyclophosphamide served
      as control. Results showed that short-term and long-term relapse and average
      prednisone dosage were similar between these two groups. It is considered that
      Chai-Ling-Tang may be a useful substitute for patients with SDNS who fail to
      respond to or manifest severe toxic effect from cytotoxic agents.

PMID- 8571922
TI  - The anti-inflammatory and anti-hyperuricemic effects of Chinese herbal formula
      danggui-nian-tong-tang on acute gouty arthritis: a comparative study with
      indomethacin and allopurinol.
AB  - The traditional Chinese antirheumatic herb Danggui-Nian-Tong-Tang (DGNTT) was
      studied comparatively with indomethacin and allopurinol to evaluate its anti
      inflammatory and antihyperuricemic effects in patients with gout. Results in this
      study did not show any significant improvement in reducing the total number of
      painful and swollen joints, articular index and pain score (P > 0.05) by
      treatment with DGNTT. Unlike allopurinol, DGNTT did not lower the high serum
      level of uric acid. In vitro study in rats showed that DGNTT significantly
      inhibits the activity of beta-glucuronidase (P < 0.05) and lysozyme release (P <
      0.01) from neutrophils. In conclusion, despite the effect of inhibition on enzyme
      release from neutrophils, DGNTT is not effective in treating acute arthritis or
      hyperuricemia.

PMID- 8571923
TI  - Anti-inflammatory activity of Taiwan folk medicine "ham-hong-chho" in rats.
AB  - "Ham-Hong-Chho" is a folk medicine in Taiwan, derived from the entire plants of
      Bidens pilosa L. var. minor (Blume) Sherff (Compositae), B. pilosa L. and B.
      chilensis DC. The anti-inflammatory effect of aqueous extracts of the three
      plants against paw edema induced by carrageenan and chronic arthritis induced by
      complete Freund's adjuvant were determined in rats. The results indicated that
      paw edema induced by carrageenan was significantly decreased by treatment with
      aqueous extracts (150 or 300 mg/kg) of all three plants (p < 0.05) and that the
      effect of Bidens pilosa var. minor was the most potent. However, only extracts
      (500 mg/kg) of B. pilosa L. var. minor and B. pilosa L. significantly decreased
      the paw edema induced by complete Freund's adjuvant (p < 0.05).

PMID- 8571924
TI  - Enhancement of nitric oxide production from activated macrophages by a purified
      form of ginsenoside (Rg1).
AB  - We studied the actions of purified ginsenosides Rg1 and Rb1 on nitric oxide
      production from macrophages and a macrophage cell line RAW264-7. Although neither
      Rg1 nor Rb1 induced nitric oxide from resting macrophages, Rg1 enhanced the
      production of nitric oxide from IFN-gamma activated-macrophages or RAW cells. Rg1
      also enhanced the production of nitric oxide from macrophages cocultured with
      nonadherent spleen cells stimulated by conA, LPS or anti-CD3. Rb1, however, did
      not significantly enhance nitric oxide production from stimulated macrophages or
      RAW cells. Rg1 enhanced the tumor cell killing by nitric oxide produced from IFN
      gamma-activated macrophages.

PMID- 8571925
TI  - Effects of Ganoderma lucidum and krestin on subset T-cell in spleen of gamma
      irradiated mice.
AB  - Effects of Ganoderma lucidum (Gl) and Krestin (PSK) extracts on spleen, thymus
      and splenocytes in gamma-irradiated mice were investigated in this study. ICR
      strain male mice were divided into five groups. Group A was the normal control.
      Group B, the experimental control, was treated with Gl. Group C, the radiation
      treatment control, was treated with whole body exposure to 4 Gy gamma-irradiation
      (RT). Group D was treated with RT and Gl. Group E was treated with RT and PSK.
      The dosage of Gl was 400 mg/day/kg body weight and PSK was 500 mg/day/kg body
      weight. Our results indicated that the relative thymus weight in groups D and E
      were higher than group C on day 28 after gamma-irradiation. Group D was the
      highest in all the experimental groups. CD4 and CD8 splenocytes in group D were
      higher than group C on days 7 and 28. Gl was better than PSK in repairing the
      damage of subset T-cells in the spleen of gamma-irradiated mice.

PMID- 8571926
TI  - Collective effect of a Chinese formula--a study of xiao-jian-zhong-tang.
AB  - Components of a traditional Chinese medicine formula Xiao-Jian-Zhong-Tang were
      divided into three groups: (1) Radix Paeoniae Lactiflorae, (2) Radix Astragali,
      and (3) Cinnamon twig, Radix Glycyrrhizae, Fructus jujubae and Saccharum
      Granorum. Extracts of each group were injected into rats to observe the blood
      pressure wave spectrum changes at the caudate artery. The whole formula was also
      extracted and injected into rats to monitor blood pressure wave spectrum changes.
      Each group has its own effect on the Fourier components of the blood pressure
      wave. The meridian effects of these herbs are the same as described in the
      Chinese medical literature, if we consider each meridian in resonance with a
      specific Fourier component. The whole formula when injected into rats had an
      effect on the Fourier components of the blood pressure wave similar to the linear
      combination of individual effect of the three herb groups when used separately.
      This may be the fundamental idea behind formula construction.

PMID- 8571927
TI  - Histological study on crude drugs pai-wei, pai-chein and indigenous species of
      Cynanchum in Taiwan.
AB  - The botanical origins of Cynanchum species (Cynanchum spp.) on the Taiwan market
      have been established by histological studies in the present paper. The results
      showed that the Chinese crude drug Pai-wei on the Taiwan market was derived from
      the dried roots of Cynanchum atratum Bunge; that of Pai-chein was derived from
      the dried roots of C. stauntonii (Decne.) Hand.-Mazz; and the Wanling-shu used
      locally in Taiwan was derived from the dried roots of C. taiwanianum Yamazaki.

PMID- 8571928
TI  - Effect of acupuncture at the Hoku point on vibration-induced finger flexion
      reflex in man: comparison between press needle technique, electroacupuncture, and
      in-situ technique.
AB  - Effects of press needle technique (PN), electroacupuncture (EA), or in-situ
      technique (IS) on vibration-induced finger flexion reflex (VFR) were examined in
      31 healthy adults. VFR, which is tonic finger flexion evoked by vibration applied
      to the finger tip, was induced by vibrating the volar side of the middle finger
      tip before and after acupuncture. Acupuncture was applied to the Hoku point on
      both sides. The three techniques, each studied on separate days, inhibited VFR
      and there was no significant difference in VFR inhibition among the three
      techniques (percentage of pre-acupuncture VFR was 71.5 +/- SE 2.2% after PN, 72.6
      +/- SE 2.4% after EA, and 75.6 +/- SE 2.8% after IS). The results suggest that
      afferent signals from muscles contracting due to electrical stimulation had no
      significant effect on the reflex arcs of VFR; and that the intradermal
      stimulation by acupuncture played a significant role in VFR inhibition.

PMID- 8571929
TI  - Non-invasive measurement of brain activity using functional MRI: toward the study
      of brain response to acupuncture stimulation.
AB  - We studied functional MRI in 15 male and 13 female normal volunteers on a
      clinical MRI system using gradient echo sequence. During the experiments, brain
      activation was induced by grasping the unilateral hand once or twice a second for
      motor tasks. A localized increase of MRI signal in the contralateral motor cortex
      was observed in 17 out of 21 cases (81%) under right hand motor task and 11 out
      of 21 cases (52%) under left hand motor task. The application of this method may
      be useful to evaluate brain response to acupuncture.

PMID- 8571930
TI  - Induction of heat-shock protein (hsp) by moxibustion.
AB  - Rats were treated by moxibustion at the point of hip muscle, and intramuscular
      temperature was kept at 40 degrees C for 15 minutes. The rats were sacrificed
      under deep anesthesia and the muscular tissues were excised immediately, three
      hours and 24 hours after stimulation. Proteins were extracted from the
      homogenized and centrifuged tissues of the stimulated rats and control rats. Two
      dimensional gel electrophoresis of the proteins was carried out. Heat-shock
      protein (hsp) with molecular weight of 70,000 (hsp 70), 85,000 (hsp 85) and
      100,000 (hsp 100) was detected in rats sacrificed three hours after the
      stimulation by moxibustion. Protein patterns were analyzed and the ratios of the
      hsps were obtained.

PMID- 8571931
TI  - Therapy and prevention of thrombotic thrombocytopenic purpura during pregnancy: a
      clinical study of 16 pregnancies.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a severe multisystem disorder of
      unknown pathogenesis, with preference to women. The mortality rate of patients
      with TTP was 90% until the introduction of plasma therapy that increased the
      survival rate to 70-80%, with minimal or no sequelae. Of the survivors, 30-60%
      suffer from relapses, often in association with precipitating factors such as
      infections, surgery, and pregnancy. Women who are either pregnant or in the
      postpartum period make up 10-25% of TTP patients, and once the disease occurs
      during a pregnancy, it tends to recur in subsequent ones. We treated five women
      who suffered at least one TTP episode during pregnancy. They had a total of 16
      pregnancies, eight of which were complicated by TTP. They suffered seven
      additional TTP episodes that were not associated with pregnancy. We assessed the
      severity of each TTP episode with a scoring system used in our previous studies.
      Presented is the course of their disease and their pregnancies, and guidelines
      for the management and prevention of TTP during pregnancy are provided.

PMID- 8571932
TI  - Two mutations in the locus control region hypersensitivity site-2 (5' HS-2) of
      haplotype 19 beta s chromosomes alter binding of trans-acting factors.
AB  - There are five major haplotypes associated with sickle cell anemia (SS).
      Individuals homozygous for haplotypes 3 (Senegal) and 31 (Saudi Arabian) have
      high fetal hemoglobin (HbF) levels (15 to 30% of total hemoglobin) whereas
      individuals homozygous for haplotypes 17 (Cameroon), 19 (Benin), and 20 (Bantu)
      have low HbF levels (1 to 10%). We previously identified several point mutations
      in the LCR 5'HS-2 that were specific for haplotype 19 beta s chromosomes
      (compared to the GenBank HUMHBB reference sequence, T-->G at position 8580, A-->G
      at position 8598, and A-->T at position 9114). We postulated that one or more of
      these mutations may alter the binding of specific trans-acting factors and
      ultimately affect the expression of HbF in these sickle cell patients. We
      performed gel mobility shift assays using 32P-end-labeled double-stranded 19mers
      corresponding to each of the LCR 5'HS-2 normal (GenBank) and mutant sequences.
      Nuclear extracts prepared from HeLa and HEL cells were used in our experiments
      and neither the normal nor mutant sequence at position 8580 bound trans-acting
      factors in either nuclear extract. The 8598 mutant increased binding of Sp1;
      using purified protein and both nuclear extracts. HEL extracts were used to
      quantify the increase in Sp1 binding to the 8598 mutation and we found an
      increase in binding of 66 and 47%, respectively, in two shifted bands. The 9114
      mutation sharply decreased binding of an unknown trans-acting factor by 74%. This
      factor was present in both HeLa and HEL nuclear extracts.

PMID- 8571933
TI  - Neonatal jaundice and molecular mutations in glucose-6-phosphate dehydrogenase
      deficient newborn infants.
AB  - Molecular mutations of the glucose-6-phosphate dehydrogenase (G6PD) gene and
      clinical manifestations of neonatal jaundice in 112 male and 50 female Chinese
      neonates with G6PD deficiency were studied. In the 112 males, the nucleotide (nt)
      1376 (G-->T) mutation was the dominant type (50.0%), followed by nt 1388 (G-->A)
      (16.1%), nt 493 (A-->G) (8.0%), nt 1024 (C-->T) (6.2%), nt 95 (A-->G) (5.4%), nt
      392 (G-->T) (1.8%), nt 487 (G-->A) (1.8%), nt 871 (G-->A) (0.9%), and nt 1360 (C-
      >T) (0.9%). The nt 871 variant has not been reported in Taiwan before. The
      occurrence rates for nt 1376, nt 1388, nt 493, nt 95, and nt 1024 mutations in
      the 50 females were 44.0%, 18.0%, 12.0%, 6.0%, and 6.0%, respectively. The type
      of G6PD mutation in 10 male and 7 female neonates has not been identified yet.
      Although G6PD deficient neonates had higher frequency of phototherapy than G6PD
      normal neonates in both sexes, a significant difference in the prevalence of
      hyperbilirubinemia (peak bilirubin > or = 15.0 mg/dl) between G6PD deficient and
      normal neonates was found only in males. Further analysis showed that duration of
      phototherapy was longer in G6PD deficient male neonates than in the control
      group, while the outcome of phototherapy was better in subjects with non-nt 1376
      mutations than subjects with the nt 1376 mutation. Most (78.3%) of the 23 G6PD
      deficient neonates who subsequently suffered from neonatal hyperbilirubinemia
      carried the nt 1376 mutation. The results of this study indicate that the
      nucleotide substitution at 1376 is the most common and important mutation for
      G6PD deficiency in Chinese neonates in Taiwan.

PMID- 8571934
TI  - Selective discharge of patients with acute myeloid leukemia during chemotherapy
      induced neutropenia.
AB  - PURPOSE: It is common practice for patients with acute myeloid leukemia (AML) to
      be observed in hospital during the entire nadir after intensive chemotherapy. In
      an attempt to lessen the likelihood of developing infections with hospital
      acquired pathogens, we usually discharge patients upon completion of chemotherapy
      and follow them as outpatients. They are readmitted if fever develops. We
      evaluated the feasibility and safety of this practice. PATIENTS AND METHODS: We
      studied 29 patients with AML (median age 40 years, range 16-63) who were treated
      with intensive remission-induction and consolidation chemotherapy. Afebrile
      patients not receiving antibiotics were discharged immediately following
      chemotherapy and were followed every 3-4 days at the day care unit. Patients were
      instructed to return immediately if fever rose to 38.2 degrees C or a fever of 38
      degrees C persisted for 2 hr. The 29 patients received a total of 86 courses.
      Following 50 courses, patients were discharged. These 50 ambulatory nadir periods
      (ANPs) were monitored. RESULTS: Median WBC and platelet counts on discharge were
      2,900 per cubic millimeter (range 300-8,300) and 137,000 per cubic millimeter
      (range 17,000-618,000), respectively. Mean traveling time from the hospital by
      car was 1.6 hr (range 15 min-3 hr). In three of the 50 ANPs (6%), patients were
      not readmitted during their entire nadir. During 47 of the ANPs, patients
      returned to the hospital (because of fever in 44 cases), a mean of 7.2 days
      (range 1.0-12.7 days) after discharge. In 45 ANPs, patients were readmitted in
      good general condition. Four patients had life-threatening complications. Two
      patients were admitted in septic shock due to delay in seeking admission, but
      rapidly recovered. Two other patients died, one of cardiogenic shock within 24 hr
      of readmission and one 24 days later. Only one of the 11 gram negative bacteria
      cultured was resistant to mezlocillin and gentamicin. After 45 ANPs, patients
      were discharged a mean of 12.2 days (range 5-42 days) following readmission. We
      estimate that approximately 383 hospital days were saved by this policy, a mean
      of 7.6 days per patient, representing 16% of total inpatient hospital days.
      CONCLUSIONS: For AML patients who are reliable and without complicating medical
      conditions, selected discharge following chemotherapy is a low-risk practice and
      may reduce the incidence of infection with resistant hospital-acquired pathogens.

PMID- 8571935
TI  - Two different mutations in codon 97 of the beta-globin gene cause Hb Malmo in
      Sweden.
AB  - An abnormal hemoglobin with increased oxygen affinity, Hb Malmo [alpha 2 beta
      297(FG4)His-->Gln], was found to cause erythrocytosis in two apparently unrelated
      Swedish families. Direct nucleotide sequencing of amplified DNA demonstrated a
      CAC-->CAA substitution in one family and a CAC-->CAG substitution in the other.
      Both mutations resulted in a His-->Gln substitution in codon 97. This finding
      prompted us to examine the possible point mutations underlying the different
      hemoglobin variants reported in the literature.

PMID- 8571936
TI  - Recombinant human interferon alpha-2b (rh IFN alpha-2b) therapy for steroid
      resistant idiopathic thrombocytopenic purpura (ITP).
AB  - The efficacy of recombinant human interferon alpha-2b (rh IFN alpha-2b) in the
      treatment of steroid resistant idiopathic thrombocytopenic purpura (ITP) was
      studied in 50 cases. Forty-one patients treated with rh IFN alpha-2b three times
      a week, six of 18 (33.3%) in the low dose group (150 x 10(4)IU: 3 MIU) and four
      of 20 (20.0%) in the high dose group (300 x 10(4)IU: 3 MIU) responded with
      platelet counts increasing to above 50 x 10(9)/L. Because of the exacerbation of
      thrombocytopenia and nasal bleeding, treatment was discontinued within 2 weeks in
      three patients out of 41 cases. On the other hand, six of nine patients (66.7%)
      treated with 3 MIU of IFN alpha-2b once a week for 8 weeks showed satisfactory
      response. Treatment with either administration schedule did not result in
      sustaining platelet counts above 50 x 10(9)/L for a long time after treatment.
      The results indicate that once a week administration schedule of rh IFN alpha-2b
      is more efficacious for platelet counts increasing for short period in patients
      who failed to respond to steroid and other medications than other schedules. The
      maintenance of this treatment schedule will allow sustained increased platelet
      levels, resulting in relief of bleeding tendency, while also being cost effective
      in comparison with other IFN treatment schedules and achieving better patient
      compliance without flu-like symptoms.

PMID- 8571937
TI  - Phospholipid composition and organization in model beta-thalassemic erythrocytes.
AB  - The membrane phospholipid organization in human red blood cells (RBC) is rigidly
      maintained by a complex system of enzymes. However, several elements of this
      system are sensitive to oxidative damage. An important component in the
      destruction of beta-thalassemic RBC is the generation of reactive oxygen species
      and the release of redox-active iron by the unpaired alpha-hemoglobin chains.
      Consequently, we hypothesized that the presence of this oxidative stress to the
      RBC membrane could lead to alterations in membrane lipid organization. Model beta
      thalassemic RBC, prepared by the introduction of excess alpha-globin in the cell,
      have previously been shown to exhibit structural and functional changes almost
      identical to those observed in beta-thalassemic cells. After 24 hr at 37 degrees
      C, the model beta thalassemic cells exhibited a significant loss of
      deformability, as measured by ektacytometric analysis, indicative of extensive
      membrane damage. However, a normal steadystate distribution of endogenous
      phospholipids was found, as evidenced by the accessibility of membrane
      phospholipids to hydrolysis by phospholipases. Similarly, the kinetics of
      transbilayer movement of spin-labeled phosphatidylserine (PS) and
      phosphatidylethanolamine (PE) in all samples was in the normal range and was not
      affected by the presence of excess alpha-globin chains. In contrast, a faster
      rate of spin-labeled phosphatidylcholine (PC) transbilayer movement was observed
      in these cells. While control RBC exhibited a complete loss of their initial (2
      mol%) lysophosphatidylcholine (LPC) levels following 24 hr of incubation at 37
      degrees C, 1.5 mol% LPC was still present in model beta-thalassemic cells,
      suggesting an altered phospholipid molecular species turnover, possibly as a
      result of an increased repair of oxidatively damaged phospholipids.

PMID- 8571938
TI  - Congenital dyserythropoietic anemias.
AB  - The congenital dyserythropoietic anemias (CDAs) are a group of relatively rare
      inherited anemias that share in common ineffective erythropoiesis and morphologic
      abnormalities of mature red blood cells and their precursors. Three major types
      of CDA and a number of variants have been described. The diagnosis and
      categorization of these disorders are facilitated by microscopic examination of
      the blood and bone marrow and by serologic testing. Management of patients
      currently consists of observation and supportive care. Because patients with CDAs
      may be at significant risk for secondary hemochromatosis, they require monitoring
      for this condition. Splenectomy may be of benefit in certain cases in which the
      anemia is particularly severe. Over the past few years advances have been made in
      understanding the pathogenesis of these disorders, and it now appears that CDA II
      results from enzymatic defects in the cellular glycosylation pathway.

PMID- 8571939
TI  - Central nervous system granulocytic sarcoma in a patient with essential
      thrombocythemia.
AB  - We report a rare case of central nervous system granulocytic sarcoma (GS) in a
      patient with essential thrombocythemia (ET). The diagnosis of GS was established
      by morphological and cytochemical findings (peroxidase and naphthol-AS-D
      chloroacetate esterase positivity) of neoplastic cells. GS was detected as an
      intracranial frontal mass 7 months before the transformation of ET in acute
      myeloid leukemia and relapsed as two extradural spinal masses during the course
      of leukemic evolution.

PMID- 8571940
TI  - Concurrent presentation of erythrocytic and megakaryocytic aplasia.
AB  - A case of a patient presenting with idiopathic concurrent erythrocytic and
      megakaryocytic aplasia is reported. The patient's response to immunosuppressive
      therapy and her bone marrow pathology clearly suggest an immune mechanism. Based
      on the lack of suppression of erythroid colony growth, several mechanisms are
      postulated. Well-established molecular and genetic evidence, along with clinical
      observations, suggests that a relationship exists between the erythrocytic and
      megakaryocytic cell lines. This may be related to a common bipotential stem cell
      or common cell surface markers. This case provides strong clinical evidence to
      support this relationship.

PMID- 8571941
TI  - Abnormally large von Willebrand factor multimers in Henoch-Schonlein purpura.
AB  - Allergic vasculitis phenomena seem to be involved in Henoch-Schonlein purpura
      (HSP). Elevated plasma levels of von Willebrand factor (vWf) are a well
      recognized feature of vasculitis and have been taken as an indication of in vivo
      endothelial cell damage. Plasma factor VIII:C and vWf levels and vWf multimeric
      pattern were studied in 8 patients with HSP, during active disease and twice
      during the remission (3 and 9 months later). Plasma vWf multimeric composition
      was evaluated using low resolution gels which better resolve large vWf multimers.
      During active disease plasma factor VIII:C, vWf:Ag, and vWf:RCoF were normal in
      5% of patients and increased in three, but in each patient, platelets appeared to
      aggregate at doses of ristocetin lower than in normals. Furthermore, all patients
      demonstrated the presence of abnormally large vWf multimers usually found only in
      platelets and endothelial cells. Three and 9 months later, during remission, in
      spite of the normalization of factor VIII:C and vWf levels, the abnormal
      multimers were still detectable, as well as hyper-responsiveness to ristocetin.
      These findings confirm that damage and/or perturbation of endothelial cells is
      associated with HSP. Moreover, the persistence of abnormality in the vWf
      multimeric pattern, when the disease is inactive, suggests that the mechanisms
      involved operate through the entire clinical course.

PMID- 8571942
TI  - Concurrent thrombotic thrombocytopenic purpura and immune thrombocytopenic
      purpura in an HIV-positive patient: case report and review of the literature.
AB  - Immune thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura
      (TTP) have each been associated with HIV infection. Sequential occurrence of
      these two diseases with a disease-free interval has been occasionally reported in
      the literature, whereas simultaneous manifestations of these two diseases have
      not been described. Here, we report an AIDS patient who was initially diagnosed
      as having TTP and showed an apparent partial response to plasmapheresis but was
      found to have a clinical course similar to ITP. Although precise mechanisms for
      the development of TTP and ITP in these patients are unclear, we offer several
      hypotheses. It is important to recognize that these two processes may be seen
      concurrently.

PMID- 8571943
TI  - Platelet activation and thrombosis: studies in a patient with essential
      thrombocythemia.
AB  - Recent advances permit the detection of activated platelets using specific
      monoclonal antibodies and flow cytometry. Nevertheless, there are few reports in
      which activated platelets have been studied over a period of time in patients at
      risk for thrombosis. Our patient S.D. has essential thrombocythemia and a
      prothrombotic state manifested in two major thrombotic episodes involving the
      portal vein and a mesenteric artery. Investigation revealed both spontaneous
      aggregation and hyperaggregability in response to ADP and the presence of
      activated platelets in platelet-rich plasma as revealed by flow cytometry.
      Interestingly, the activated platelets were recognized by an anti-RIBS ("receptor
      induced binding site") monoclonal antibody that recognized bound fibrinogen but
      not by antibodies reactive with antigens whose presence on the platelet surface
      was secretion dependent. Treatment with aspirin inhibited spontaneous platelet
      aggregation but had little effect on the activated platelet profile. A change of
      therapy to ticlopidine suppressed expression of platelet activation markers.
      Treatment with ticlopidine has continued for 1 year so far without further
      thrombotic complications.

PMID- 8571945
TI  - High-dose intravenous desferrioxamine (DFO) delivery in four thalassemic patients
      allergic to subcutaneous DFO administration.
AB  - To test the hypothesis that allergy to desferrioxamine is not an immunologic
      mechanism, but arises from a local effect on the dermal mast cell, we have
      treated four patients who were not receiving chelation therapy because of
      hypersensitivity to standard subcutaneous (SC) therapy, with high-dose
      desferrioxamine (DFO) by the intravenous (IV) route. Three patients had central
      venous access ports implanted on the anterior chest wall. The fourth patient had
      the therapy delivered by the peripheral vein route. All patients had the drug
      delivered via an elastomeric infusor. Intravenous therapy was successful for all
      patients. During one year of therapy no local or systemic allergic manifestations
      were noted. In addition, no impairment of hearing or vision or any catheter
      complications were reported. A very high level of patient compliance to the
      therapy resulted in dramatically decreased iron stores and ferritin levels (2,759
      ng/ml to 717.5 ng/ml) and a significant improvement in the clinical status of all
      patients. The absence of allergic episodes in this patient group after 1 year of
      i.v. therapy would strongly support the hypothesis that SC DFO allergy is related
      to a direct effect on dermal mast cells and is not an immunological reaction.
      This study suggests that patients with severe allergy to SC DFO can therefore
      safely receive their chelation therapy via the i.v. route.

PMID- 8571944
TI  - Acute myelofibrosis terminating in acute lymphoblastic leukemia: case report and
      review of the literature.
AB  - Acute myelofibrosis (AMF), as defined by an acute panmyelopathy associated with
      marked megakaryocytic hyperplasia and marrow fibrosis, appears to be a stem cell
      disorder. Even though it is most difficult to distinguish from various
      myeloproliferative and myelodysplastic disorders as well as acute myelogenous
      leukemia, it has rarely been reported to terminate as acute lymphoblastic
      leukemia (ALL). Only five cases have been reported in the literature; two from
      the pediatric literature and only three from the adult literature. Of the three
      adult cases, two were defined by light microscopy alone. Among the cases with
      follow-up (3/5), all died within 2 weeks to 2 months of diagnosis. We report an
      additional case in an adult; the ALL was defined by morphology, flow cytometric
      immunophenotyping, and cytogenetic analysis. The interval from diagnosis of AMF
      to ALL was 3 months. Our patient was treated with standard therapy for ALL, was
      in complete remission at last follow-up (3 months off maintenance therapy), and
      represents the only reported case who attained a complete remission. There are
      too few cases to determine the prognostic significance of termination of AMF in
      an acute leukemia of lymphoid origin vs. myeloid origin.

PMID- 8571946
TI  - Refractory thrombotic thrombocytopenic purpura treated with cyclosporine.

PMID- 8571947
TI  - Sequence analysis of HTLV-1 provirus associated with adult T-cell
      leukemia/lymphoma in Hong Kong.

PMID- 8571948
TI  - Management of iron overload with a disposable multi-day delivery system.

PMID- 8571949
TI  - Concurrent epiphyseal fracture and leukemia in a patient treated with growth
      hormone.

PMID- 8571950
TI  - Phenotypic analysis of blood neutrophils in a patient with chronic idiopathic
      neutropenia and favorable response to G-CSF treatment.

PMID- 8571951
TI  - Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia
      sulfate-transporter gene (DTDST): evidence for a phenotypic series involving
      three chondrodysplasias.
AB  - Atelosteogenesis type II (AO II) is a neonatally lethal chondrodysplasia whose
      clinical and histological characteristics resemble those of another
      chondrodysplasia, the much less severe diastrophic dysplasia (DTD). The
      similarity suggests a shared pathogenesis involving lesions in the same
      biochemical pathway and perhaps the same gene. DTD is caused by mutations in the
      recently identified diastrophic dysplasia sulfate-transporter gene (DTDST). Here,
      we report that AOII patients also have DTDST mutations, which lead to defective
      uptake of inorganic sulfate and insufficient sulfation of macromolecules by
      patient mesenchymal cells in vitro. Together with our recent observation that a
      third even more severe chondrodysplasia, achondrogenesis type IB, is also caused
      by mutations in DTDST, these results demonstrate a phenotypic series of three
      chondrodysplasias of increasing severity caused by lesions in a single sulfate
      transporter gene. The severity of the phenotype appears to be correlated with the
      predicted effect of the mutations on the residual activity of the DTDST protein.

PMID- 8571952
TI  - Defects in the DNA repair and transcription gene ERCC2(XPD) in
      trichothiodystrophy.
AB  - Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by
      brittle hair with reduced sulfur content, ichthyosis, peculiar face, and mental
      and growth retardation. Clinical photosensitivity is present in approximately 50%
      of TTD patients but is not associated with an elevated frequency of cancers.
      Previous complementation studies show that the photosensitivity in nearly all of
      the studied patients is due to a defect in the same genetic locus that underlies
      the cancer-prone genetic disorder xeroderma pigmentosum group D (XP-D).
      Nucleotide-sequence analysis of the ERCC2 cDNA from three TTD cell strains
      (TTD1V1, TTD3VI, and TTD1RO) revealed mutations within the region from amino acid
      713-730 and within previously identified helicase functional domains. The various
      clinical presentations and DNA repair characteristics of the cell strains can be
      correlated with the particular mutations found in the ERCC2 locus. Mutations of
      Arg658 to either His or Cys correlate with TTD cell strains with intermediate UV
      sensitivity, mutation of Arg722 to Trp correlates with highly UV-sensitive TTD
      cell strains, and mutation of Arg683 to Trp correlates with XP-D. Alleles with
      mutation of Arg616 to Pro or with the combined mutation of Leu461 to Val and
      deletion of 716-730 are found in both XP-D and TTD cell strains.

PMID- 8571953
TI  - Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families:
      results of an international study.
AB  - Several BRCA1 mutations have now been found to occur in geographically diverse
      breast and ovarian cancer families. To investigate mutation origin and mutation
      specific phenotypes due to BRCA1, we constructed a haplotype of nine polymorphic
      markers within or immediately flanking the BRCA1 locus in a set of 61
      breast/ovarian cancer families selected for having one of six recurrent BRCA1
      mutations. Tests of both mutations and family-specific differences in age at
      diagnosis were not significant. A comparison of the six mutations in the relative
      proportions of cases of breast and ovarian cancer was suggestive of an effect (P
      = .069), with 57% of women presumed affected because of the 1294 del 40 BRCA1
      mutation having ovarian cancer, compared with 14% of affected women with the
      splice-site mutation in intron 5 of BRCA1. For the BRCA1 mutations studied here,
      the individual mutations are estimated to have arisen 9-170 generations ago. In
      general, a high degree of haplotype conservation across the region was observed,
      with haplotype differences most often due to mutations in the short-tandem-repeat
      markers, although some likely instances of recombination also were observed. For
      several of the instances, there was evidence for multiple, independent, BRCA1
      mutational events.

PMID- 8571954
TI  - A 10-bp deletion in the apolipoprotein epsilon gene causing apolipoprotein E
      deficiency and severe type III hyperlipoproteinemia.
AB  - Type III hyperlipoproteinemia (HLP) is usually associated with homozygosity for
      apolipoprotein (apo) E2. We identified a 30-year-old male German of Hungarian
      ancestry with severe type III HLP and apo E deficiency. The disease was expressed
      in an extreme phenotype with multiple cutaneous xanthomas. Apo E was detectable
      only in trace amounts in plasma but not in the different lipoprotein fractions.
      Direct sequencing of PCR-amplified segments of the apo epsilon gene identified a
      10-bp deletion in exon 4 (bp 4037-4046 coding for amino acids 209-212 of the
      mature protein). The mutation is predictive for a reading frameshift introducing
      a premature stop codon (TGA) at amino acid 229. By western blot analysis, we
      found small amounts of a truncated apo E in the patient's plasma. Family analysis
      revealed that the proband was homozygous--and 10 of 24 relatives were
      heterozygous--for the mutation. Heterozygotes had, as compared to unaffected
      family members, significantly higher triglycerides (TG), very low-density
      lipoprotein (VLDL) cholesterol and a significantly higher VLDL cholesterol-to
      serum TG ratio, which is indicative of a delayed remnant catabolism. We propose
      that the absence of a functionally active apo E is the cause of the severe type
      III HLP in the patient and that the mutation, even in a single dose in
      heterozygotes, predisposes in variable severity to the phenotypic expression of
      the disease.

PMID- 8571955
TI  - Modulation of the phenotype in dominant erythropoietic protoporphyria by a low
      expression of the normal ferrochelatase allele.
AB  - Erythropoietic protoporphyria (EPP) is a monogenic inherited disorder of the heme
      biosynthetic pathway due to ferrochelatase (FC) deficiency. EPP is generally
      considered to be transmitted as an autosomal dominant disease with incomplete
      penetrance, although autosomal recessive inheritance has been documented at the
      enzymatic and molecular level in some families. In the dominant form of EPP,
      statistical analysis of FC activities documented a significantly lower mean value
      in patients than in asymptomatic carriers, suggesting a more complex mode of
      inheritance. To account for these findings, we tested a multiallelic inheritance
      model in one EPP family in which the enzymatic data were compatible with this
      hypothesis. In this EPP family, the specific FC gene mutation was an exon 10
      skipping (delta Ex10), resulting from a G deletion within the exon 10 consensus
      splice donor site. The segregation of all FC alleles within the family was
      followed using the delta Ex10 mutation and a new intragenic dimorphism (1520
      C/T). mRNAs transcribed from each FC allele were then subjected to relative
      quantification by a primer extension assay and to absolute quantification by a
      ribonuclease protection assay. The data support the hypothesis that in this
      family the EPP phenotype results from the coinheritance of a low output normal FC
      allele and a mutant delta Ex10 allele.

PMID- 8571957
TI  - Molecular analysis of a series of alleles in humans with reduced activity at the
      triosephosphate isomerase locus.
AB  - Individuals with 50% of expected triosephosphate isomerase (TPI) enzyme activity
      have been previously identified in families during the screening of approximately
      2,000 newborn children for quantitative variation in activity of 12 erythrocyte
      enzymes. The frequency of the trait was 9/1,713 individuals in the Caucasian
      population and 7/168 individuals among the African-American population studied.
      Genetic transmission of the trait was confirmed in all families. The frequency of
      the presumptive deficiency allele(s) at the TPI locus was greater than expected,
      given the reported incidence of clinical TPI deficiency. We report the molecular
      characterization of the variant alleles from seven African-American and three
      Caucasian individuals in this group of unrelated individuals. Three amino acid
      substitutions--a Gly-->Ala substitution at residue 72, a Val-->Met at residue
      154, and a previously described Glu-->Asp substitution at residue 104--were
      identified in the Caucasian individuals. The substitutions occur at residues that
      are not directly involved in the active site but are highly conserved through
      evolutionary time, suggesting important roles for these residues in maintenance
      of subunit structure and conformation. The variant allele in the seven African
      American individuals had nucleotide changes at positions -8 and -5 (5' of) from
      the transcription-initiation site. In three of these individuals, an additional T
      ->G substitution was detected in a TATA box-like sequence located 24 nucleotides
      5' of the transcription-initiation site and on the same chromosome as the -5/-8
      substitutions. Thus, molecular alterations at the TPI locus were detected in 10
      unrelated individuals in whom segregation of a phenotype of reduced TPI activity
      previously had been identified.

PMID- 8571956
TI  - Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal
      cancer cluster at the exonic region 15-16.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is a common autosomal dominant
      cancer susceptibility condition. Inherited mutations in at least four DNA
      mismatch repair genes, hMSH2, hMLH1, hPMS1, and hPMS2, are known to cause HNPCC.
      In this study we used denaturing gradient gel electrophoresis (DGGE) to screen
      for hMLH1 mutations in 34 unrelated HNPCC families (30 Dutch, 3 Italian, and 1
      Danish). Ten novel pathogenic germ-line mutations (seven affecting splice sites,
      two frameshifts, and one in-frame deletion of a single amino acid) have been
      identified in 12 (35%) of these families. In a previous study, hMSH2 mutations
      were found in 21% of the same families. While the spectrum of mutations at the
      hMSH2 gene among HNPCC patients appears heterogeneous, a cluster of hMLH1
      mutations has been found in the region encompassing exons 15 and 16, which
      accounts for 50% of all the independent hMLH1 mutations described to date and for
      > 20% of the unrelated HNPCC kindreds here analyzed. This unexpected finding has
      a great practical value in the clinical scenario of genetic services.

PMID- 8571958
TI  - Novel muscle chloride channel mutations and their effects on heterozygous
      carriers.
AB  - Mutations within CLCN1, the gene encoding the major skeletal muscle chloride
      channel, cause either dominant Thomsen disease or recessive Becker-type myotonia,
      which are sometimes difficult to discriminate, because of reduced penetrance or
      lower clinical expressivity in females. We screened DNA of six unrelated Becker
      patients and found four novel CLCN1 mutations (Gln-74-Stop, Tyr-150-Cys, Tyr-261
      Cys, and Ala-415-Val) and a previously reported 14-bp deletion. Five patients
      were homozygous for the changes (Gln-74-Stop, Ala-415-Val, and 14-bp deletion),
      four of them due to parental consanguinity. The sixth patient revealed compound
      heterozygosity for Tyr-150-Cys and Tyr-261-Cys. Heterozygous carriers of the
      Becker mutations did not display any clinical symptoms of myotonia. However, all
      heterozygous males, but none of the heterozygous females, exhibited myotonic
      discharges in the electromyogram suggesting (i) a gene dosage effect of the
      mutations on the chloride conductance and (ii) male predominance of subclinical
      myotonia. Furthermore, we report a novel Gly-200-Arg mutation resulting in a
      dominant phenotype in a male and a partially dominant phenotype in his mother. We
      discuss potential causes of the gender preference and the molecular mechanisms
      that may determine the mode of inheritance.

PMID- 8571959
TI  - Longitudinal study of a heteroplasmic 3460 Leber hereditary optic neuropathy
      family by multiplexed primer-extension analysis and nucleotide sequencing.
AB  - Nucleotide-sequencing and multiplexed primer-extension assays have been used to
      quantitate the mutant-allele frequency in 14 maternal relatives, spanning three
      generations, from a family that is heteroplasmic for the primary Leber hereditary
      optic neuropathy (LHON) mutation at nucleotide 3460 of the mitochondrial genome.
      There was excellent agreement between the values that were obtained with the two
      different methods. The longitudinal study shows that the mutant-allele frequency
      was constant within individual family members over a sampling period of 3.5
      years. Second, although there was an overall increase in the mutant-allele
      frequency in successive generations, segregation in the direction of the mutant
      allele was not invariant, and there was one instance in which there was a
      significant decrease in the frequency from parent to offspring. From these two
      sets of results, and from previous studies of heteroplasmic LHON families, we
      conclude that there is no evidence for a marked selective pressure that
      determines the replication, segregation, or transmission of primary LHON
      mutations to white blood cells and platelets. Instead, the mtDNA molecules are
      most likely to replicate and segregate under conditions of random drift at the
      cellular level. Finally, the pattern of transmission in this maternal lineage is
      compatible with a developmental bottleneck model in which the number of
      mitochondrial units of segregation in the female germ line is relatively small in
      relation to the number of mtDNA molecules within a cell. However, this is not an
      invariant pattern for humans, and simple models of mitochondrial gene
      transmission are inappropriate at the present time.

PMID- 8571960
TI  - Gene structure, DNA methylation, and imprinted expression of the human SNRPN
      gene.
AB  - The human SNRPN (small nuclear ribonucleoprotein polypeptide N) gene is one of a
      gene family that encode proteins involved in pre-mRNA splicing and maps to the
      smallest deletion region involved in the Prader-Willi syndrome (PWS) within
      chromosome 15q11-q13. Paternal only expression of SNRPN has previously been
      demonstrated by use of cell lines from PWS patients (maternal allele only) and
      Angelman syndrome (AS) patients (paternal allele only). We have characterized two
      previously unidentified 5' exons of the SNRPN gene and demonstrate that exons -1
      and 0 are included in the full-length transcript. This gene is expressed in a
      wide range of somatic tissues and at high, approximately equal levels in all
      regions of the brain. Both the first exon of SNRPN (exon -1) and the putative
      transcription start site are embedded within a CpG island. This CpG island is
      extensively methylated on the repressed maternal allele and is unmethylated on
      the expressed paternal allele, in a wide range of fetal and adult somatic cells.
      This provides a quick and highly reliable diagnostic assay for PWS and AS, which
      is based on DNA-methylation analysis that has been tested on > 100 patients in a
      variety of tissues. Conversely, several CpG sites approximately 22 kb downstream
      of the transcription start site in intron 5 are preferentially methylated on the
      expressed paternal allele in somatic tissues and male germ cells, whereas these
      same sites are unmethylated in fetal oocytes. These findings are consistent with
      a key role for DNA methylation in the imprinted inheritance and subsequent gene
      expression of the human SNRPN gene.

PMID- 8571962
TI  - Aneuploidy in human sperm: the use of multicolor FISH to test various theories of
      nondisjunction.
AB  - While it is known that all chromosomes are susceptible to meiotic nondisjunction,
      it is not clear whether all chromosomes display the same frequency of
      nondisjunction. By use of multicolor FISH and chromosome-specific probes, the
      frequency of disomy in human sperm was determined for chromosomes 1, 2, 4, 9, 12,
      15, 16, 18, 20, and 21, and the sex chromosomes. A minimum of 10,000 sperm nuclei
      were scored from each of five healthy, chromosomally normal donors for every
      chromosome studied, giving a total of 418,931 sperm nuclei. The mean frequencies
      of disomy obtained were 0.09% for chromosome 1; 0.08% for chromosome 2; 0.11% for
      chromosome 4; 0.14% for chromosome 9; 0.16% for chromosome 12; 0.11% for
      chromosomes 15, 16, and 18; 0.12% for chromosome 20; 0.29% for chromosome 21; and
      0.43% for the sex chromosomes. Data for chromosomes 1, 12, 15, and 18, and the
      sex chromosomes have been published elsewhere. When the mean frequencies of
      disomy were compared, the sex chromosomes and chromosome 21 had significantly
      higher frequencies of disomy than that of any other autosome studied. These
      results corroborate the pooled data obtained from human sperm karyotypes and
      suggest that the sex chromosome bivalent and the chromosome 21 bivalent are more
      susceptible to nondisjunction during spermatogenesis. From these findings,
      theories proposed to explain the variable incidence of nondisjunction can be
      supported or discarded as improbable.

PMID- 8571961
TI  - Map refinement of locus RP13 to human chromosome 17p13.3 in a second family with
      autosomal dominant retinitis pigmentosa.
AB  - In order to elucidate the genetic basis of autosomal dominant retinitis
      pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British
      descent, we assessed linkage between the UCLA-RP09 adRP gene and numerous genetic
      loci, including eight adRP candidate genes, five anonymous adRP-linked DNA loci,
      and 20 phenotypic markers. Linkage to the UCLA-RP09 disease gene was excluded for
      all eight candidate genes analyzed, including rhodopsin (RP4) and peripherin/RDS
      (RP7), for the four adRP loci RP1, RP9, RP10 and RP11, as well as for 17
      phenotypic markers. The anonymous DNA marker locus D17S938, linked to adRP locus
      RP13 on chromosome 17p13.1, yielded a suggestive but not statistically
      significant positive lod score. Linkage was confirmed between the UCLA-RP09 adRP
      gene and markers distal to D17S938 in the chromosomal region 17p13.3. A
      reanalysis of the original RP13 data from a South African adRP family of British
      descent, in conjunction with our UCLA-RP09 data, suggests that only one adRP
      locus exists on 17p but that it maps to a more telomeric position, at band
      17p13.3, than previously reported. Confirmation of the involvement of RP13 in two
      presumably unrelated adRP families, both of British descent, suggests that this
      locus is a distinct adRP gene in a proportion of British, and possibly other,
      adRP families.

PMID- 8571963
TI  - Genetic evidence for the neuronal nitric oxide synthase gene (NOS1) as a
      susceptibility locus for infantile pyloric stenosis.
AB  - The etiological role of the gene for neuronal nitric oxide synthase (NOS1) in
      infantile pyloric stenosis (PS) was investigated by analysis of two intragenic
      polymorphisms (NOS1a and NOS1b) in 27 families. There was significant overall
      transmission disequilibrium between PS and NOS1a (P = .006). Consideration of
      each allele independently revealed a highly significant tendency for allele 7
      (210 bp) to be preferentially transmitted to the affected offspring (P = .0006).
      These observations suggest that NOS1 is a susceptibility locus for PS.

PMID- 8571964
TI  - Sex influences on the penetrance of HLA shared-epitope genotypes for rheumatoid
      arthritis.
AB  - The association between rheumatoid arthritis (RA) and HLA DRB1 alleles may arise
      through linkage disequilibrium with a disease locus or the direct involvement of
      HLA alleles in RA. In support of the latter possibility, the shared-epitope
      hypothesis has been postulated, stating that conformationally similar DR beta
      chains encoded by several DRB1 alleles confer disease susceptibility. To examine
      these alternative hypotheses of marker-disease association and to investigate
      gender differences in RA susceptibility, we analyzed the distributions of PCR
      based DRB1 genotypes of 309 Caucasian RA patients and 283 Caucasian controls.
      Initially, the marker-association-segregation chi 2 method was used to evaluate
      evidence for linkage disequilibrium and the direct involvement of markers DR4
      Dw4, DR4 Dw14, and DR1 in RA susceptibility. Additional shared-epitope models
      that grouped DRB1 alleles into five classes (*0401, *0404/*0102,
      *0405/*0408/*0101, *1001, and all others) and postulated relationships between
      genotypes and RA susceptibility were also fitted to observed genotypic
      distributions by the method of minimal chi 2. For females, a linkage
      disequilibrium model provided a good fit to the data, as did a shared-epitope
      model with RA most penetrant among individuals with the *0401,*0401 genotype. For
      males, the best model indicated highest RA penetrance among shared-epitope
      compound heterozygotes. Clinically, male RA patients had more subcutaneous
      nodules and greater use of slowly acting antirheumatic drugs, while female RA
      patients had earlier disease onset. This study therefore suggests that sex
      related factors influence the RA penetrance associated with DRB1 shared-epitope
      genotypes and that DRB1 effects on RA prognosis and pathogenesis should be
      considered separately for men and women.

PMID- 8571965
TI  - Major-locus contributions to variability of the craniofacial feature dystopia
      canthorum in Waardenburg syndrome.
AB  - We used segregation analysis to investigate the genetic basis of variation in
      dystopia canthorum, one of the key diagnostic features of Waardenburg syndrome
      type 1 (WS1). We sought to determine whether the W-index, a quantitative measure
      of this craniofacial feature, is influenced primarily either by allelic variation
      in the PAX3 disease gene or other major loci, by polygenic background effects, or
      by all of these potential sources of genetic variation. We studied both WS1
      affected individuals and their WS1-unaffected relatives. After adjustment of the
      W-index for WS1 disease status, segregation analyses by the regression approach
      indicated major-locus control of this variation, although residual parent
      offspring and sib-sib correlations are consistent with additional (possibly
      polygenic) effects. Separate analyses of WS1-affected and WS1-unaffected
      individuals suggest that epistatic interactions between disease alleles at the
      PAX3 WS1 locus and a second major locus influence variation in dystopia
      canthorum. Our approach should be applicable for assessing the genetic
      architecture of variation associated with other genetic diseases.

PMID- 8571966
TI  - The need for anonymous genetic counseling and testing.
AB  - Concerns are mounting about the risks of genetic discrimination resulting from
      the release of predictive and presymptomatic genetic test results to employers,
      insurers, and others. The ability to keep this information confidential is
      questionable, particularly in view of the expansion of electronic medical
      databases. One solution is to afford individuals access to anonymous genetic
      counseling and testing. Probands would be identified only by a code that would
      not reveal personal information, and test results would be stored, retrieved, and
      released solely on the basis of this code. The experience with anonymous HIV
      testing, while not completely analogous, suggests that such an approach would be
      both practical and effective.

PMID- 8571967
TI  - Establishing the robustness of short-tandem-repeat statistics for forensic
      applications.
AB  - Before the introduction of a four-locus multiplex short-tandem-repeat (STR)
      system into casework, an extensive series of tests were carried out to determine
      robust procedures for assessing the evidential value of a match between crime and
      suspect samples. Twelve databases were analyzed from the three main ethnic groups
      encountered in casework in the United Kingdom: Caucasians, Afro-Caribbeans, and
      Asians from the Indian subcontinent. Independence tests resulted in a number of
      significant results, and the impact that these might have on forensic casework
      was investigated. It is demonstrated that previously published methods provide a
      simple procedure for correcting allele frequencies--and that this leads to
      conservative casework estimates of evidential value.

PMID- 8571968
TI  - Gametogenesis processes and multilocus gene identity by descent.
AB  - With few exceptions, the determination of unconditional probability of genes
      shared identical by descent (IBD) by relatives can be very difficult, especially
      if the relationship is complex or if multiple loci are involved. It is
      particularly difficult if one needs the IBD probability in a explicit form,
      expressed in terms of interlocus recombination fractions. In this paper, I will
      further extend the concept of gametogenesis process introduced elsewhere and
      indicate that it completely determines the gene IBD events of interest in
      pedigrees. I will demonstrate that the gametogenesis process not only serves as a
      convenient conceptual framework in considering IBD events in pedigrees but also
      provides a simple yet powerful tool to solve a wide range of seemingly difficult
      problems. In particular, I consider the problem of multilocus IBD probability for
      relative pairs, k siblings, and a group of pedigree members. In addition, I
      consider the problem of multilocus autozygosity probability and the problem of
      gene preservation in close relatives.

PMID- 8571969
TI  - A novel mutation (Gln266-->His) in the alpha 1 subunit of the inhibitory glycine
      receptor gene (GLRA1) in hereditary hyperekplexia.

PMID- 8571970
TI  - Alterations of chromosome 11q13 in cervical carcinoma cell lines.

PMID- 8571971
TI  - Association between prostate cancer in black Americans and an allele of the
      PADPRP pseudogene locus on chromosome 13.

PMID- 8571972
TI  - Multiple independent origins of the COII/tRNA(Lys) intergenic 9-bp mtDNA deletion
      in aboriginal Australians.

PMID- 8571973
TI  - Nomenclature for inherited diseases of the retina.

PMID- 8571974
TI  - Certificates of confidentiality.

PMID- 8571975
TI  - Medicaid physician participation: patients, poverty, and physician self-interest.

PMID- 8571976
TI  - Medical futility and implications for physician autonomy.

PMID- 8571978
TI  - Conflicts of interest in Canadian health care law.

PMID- 8571977
TI  - Strains in the fiduciary metaphor: divided physician loyalties and obligations in
      a changing health care system.

PMID- 8571979
TI  - Adversarial medical and scientific testimony and lay jurors: a proposal for
      medical malpractice reform.

PMID- 8571980
TI  - Negligent infliction of emotional distress: a focus on relationships.

PMID- 8571981
TI  - A computer-assisted molecular epidemiologic approach to confronting the
      reemergence of tuberculosis.
AB  - Molecular epidemiologic approaches have provided important insights into the
      pathogenesis and epidemiology of tuberculosis. However, continued progress in
      this field will be reliant on the development of computerized information
      management systems capable of analyzing large numbers of bacterial DNA
      fingerprints and incorporating this with data collected as part of conventional
      disease surveillance. The specific attributes of these computer systems must be
      tailored to the nature and scope of the research question. In this article, the
      authors describe a system being used for the surveillance of Mycobacterium
      tuberculosis strains in San Francisco. The current performance characteristics
      are described, and potential future developmental directions are outlined. This
      system demonstrates several general principles of computerized molecular
      epidemiology that are likely to be of increasing applicability to a variety of
      pathogens.

PMID- 8571982
TI  - The changing epidemiology of foodborne diseases.
AB  - The epidemiology of foodborne diseases in the United States have changed in
      recent decades as new pathogens have emerged, the food supply has changed, and
      the number of people with heightened susceptibility to foodborne diseases has
      increased. Emerging pathogens are those that have recently increased or are
      likely to increase within 2 decades. Emergency is often the consequence of
      changes in some aspect of the social environment. The global economy, for
      example, has facilitated the rapid transport of perishable foods, increasing the
      potential for exposure to foodborne pathogens from other parts of the world.
      Other factors altering foodborne disease patterns are the types of food that
      people eat, the sources of those foods, and the possible decline in public
      awareness of safe food preparation practices. Aging, extension of life expectancy
      for the chronically ill through medical technology, and the AIDS epidemic have
      increased the public health impact of foodborne diseases because they increase
      the proportion of the population susceptible to severe illness after infection
      with a foodborne pathogen. The evolving epidemiology of foodborne diseases must
      be monitored and understood to implement appropriate prevention technologies.

PMID- 8571983
TI  - Addressing the challenges of emerging infectious disease.
AB  - Through the recent examples of diphtheria in the former Soviet Union, plague in
      India, and trends in pneumonia mortality in the United States, the author, in
      this article, illustrates issues in emerging infectious diseases. The Centers for
      Disease Control's plan, Addressing Emerging Infectious Disease Threats: A
      Prevention Strategy for the United States, is summarized. Initial efforts to
      implement this plan are described, with particular focus on the development of
      Emerging Infections Programs, which are conducting epidemiologic and laboratory
      projects on several infectious diseases, including invasive bacterial diseases,
      unexplained deaths, foodborne diseases, and ehrlichiosis in four population-based
      sites in the United States.

PMID- 8571984
TI  - Simian immunodeficiency virus variants: threat of new lentiviruses.
AB  - Infection in humans with the lentivirus HIV-1 typically results in the
      development of a chronic disease state characterized by the slow decline of CD4+
      lymphocytes, the development of immunosuppression, and the development of
      opportunistic infections, ultimately leading to death. Although the average
      course of disease runs approximately 10 years, shorter and longer progression
      times have been noted. These alterations are presumed to be, at least partially,
      a factor of viral variation. The simian immunodeficiency viruses (SIVs) are the
      nonhuman primate counterparts to HIV. Several of these isolates, including SIV
      from sooty mangabey monkeys, induce a remarkably similar disease in Asian
      macaques. Recently, variants of SIV from sooty mangabey monkeys and SIV from
      African green monkeys have been described, which are increasingly more
      pathogenic. As in HIV-1 infections, this is probably due to genetic variation. On
      the basis of these findings, atypical viruses with tremendous pathogenic
      potential can arise from apathogenic or moderately pathogenic viruses.

PMID- 8571985
TI  - Does Lyme disease occur in the south?: a survey of emerging tick-borne infections
      in the region.
AB  - Lyme disease is the most common arthropod-borne infection in the United States.
      However, the risk of infection varies widely by geographic region. In the South,
      Borrelia burgdorferi has been identified in ticks and small mammals, but
      transmission of the agent to humans has not been documented. The Lyme disease
      like disorder reported from the region may have another etiology.

PMID- 8571986
TI  - The reemergence of serious group A streptococcal infections and acute rheumatic
      fever.
AB  - Acute rheumatic fever and life-threatening group A streptococcal infections have
      reemerged during the past 15 years to once again become a serious health threat
      in the developed countries of the world. Reports of outbreaks of acute rheumatic
      fever in many parts of this country and others have shattered the complacency
      that the health-care community had acquired related to this devastating sequela
      of streptococcal pharyngitis. Invasive streptococcal infections, often associated
      with loss of limbs of life despite optimal antibiotic therapy, have underscored
      the potential virulence of these organisms. A new clinical entity, streptococcal
      toxic shock syndrome, has emerged as a consequence of the new invasive strains of
      group A streptococci. In this article, the authors summarize the recent changes
      in the epidemiology of group A streptococcal infections and rheumatic fever and
      review the potential reasons for the increased virulence of these organisms. In
      addition, they discuss prospects for a streptococcal M protein vaccine designed
      to control these infections and their sequelae.

PMID- 8571987
TI  - Lessons learned from the hantaviruses and other hemorrhagic fever viruses.
AB  - In recent years, numerous previously known infections pathogens and their
      associated diseases have been recognized. Among these newly identified agents are
      the viruses that cause the hemorrhagic fevers, including Sin Nombre virus, the
      etiologic agent of the 1993 outbreak of hantavirus pulmonary syndrome in the
      American Southwest. Epidemiologic and laboratory investigations of the
      hemorrhagic fevers and their etiologic agents provide lessons that may be used
      collectively as a paradigm of the nature of emerging and re-emerging infectious
      diseases.

PMID- 8571988
TI  - Reasons for the emergence of antibiotic resistance.
AB  - The ability of many different species of bacteria, including those that cause
      diseases in humans, to resist the inhibitory action of antimicrobial agents has
      become a global problem. Resistance continues to spread not only in nosocomial
      pathogens but in several key community-acquired organisms as well. Appropriate
      control measures for such resistant organisms depend in part on the pathways by
      which resistance has arisen. Unfortunately, these pathways differ greatly from
      organism to organism and setting to setting. In addition, although the
      epidemiology of resistant organisms sometimes is similar to that of susceptible
      organisms of the same kind, in some situations it may be quite different. In this
      article, the authors highlight some of the pathways leading to the development of
      resistance in bacteria, the importance of antimicrobial use, and the relevance of
      these mechanisms to measures for the control of resistant bacteria in hospital
      and community settings.

PMID- 8571989
TI  - Specific inappropriate acts in the publication process.

PMID- 8571990
TI  - Umbilical artery Doppler velocimetry: clinical utility in high-risk pregnancies.
AB  - An abnormal result of an umbilical artery Doppler study reflects the presence of
      placental vascular pathologic mechanisms and identifies pregnancies at increased
      risk for perinatal mortality. Recent reviews of the clinical utility of umbilical
      artery Doppler study have concluded that it should not be routinely used as a
      screening modality for the general obstetric population and have suggested that
      further research is required. However, metaanalysis of published peer-reviewed
      and randomized controlled trials indicates that its use in high-risk pregnancies
      is associated with a significant decrease in perinatal mortality without an
      increase in the rate of inappropriate obstetric intervention. This clinical
      opinion serves to underscore the relevance of umbilical artery Doppler
      velocimetry to clinical practice and to suggest that an abnormal result of an
      umbilical artery Doppler study should be added to the current list of indications
      for intensive fetal surveillance.

PMID- 8571991
TI  - Early detection of ovarian carcinoma with transvaginal color Doppler
      ultrasonography.
AB  - OBJECTIVE: Our purpose was to assess the potentials and limitations of the early
      detection of ovarian cancer in protocols that involve transvaginal color Doppler
      ultrasonography. STUDY DESIGN: Retrospective analysis was performed on the data
      from 206 referred patients who either had surgical or clinical follow-up of
      ovarian masses evaluated by transvaginal color Doppler ultrasonography. Most of
      the patients were referrals or had risk factors. RESULTS: In this series of 206
      patients, 26 ovarian cancers were detected, > 70% of which were stage I or II.
      CONCLUSION: Transvaginal color Doppler ultrasonography is capable of early
      detection of ovarian carcinoma. An improved detection rate may be realized with
      better identification of high-risk patients who should be studied with
      transvaginal color Doppler ultrasonography.

PMID- 8571992
TI  - Serum tumor marker immunoassays in gynecologic oncology: establishment of
      reference values.
AB  - OBJECTIVE: Our purpose was to establish reference values for six monoclonal
      antibody-based serum immunoassays applied in patients with carcinoma of the
      female genital tract. STUDY DESIGN: Sera from 938 healthy women (median age 48.0
      years, range 37 to 76 years) were assayed for levels of CA 125, CA 15.3 (two
      methods), CA M29, CA M26, and mucin-like cancer antigen (MCA). RESULTS: Reference
      values, defined as those including 95% of healthy controls, were in women with
      unknown menopausal status as follows: CA 125, 37 U/ml; CA 15.3 (Centocor), 33
      U/ml; CA 15.3 (Boehringer Mannheim), 28 U/ml; CA M26, 83 U/ml; CA M29, 13 U/ml;
      and MCA, 19 U/ml. Postmenopausal values were significantly lower for CA 125 and
      CA M26 and significantly higher for CA M29 and CA 15.3 (both methods). MCA serum
      levels were age independent. CONCLUSION: Reference values found were not in
      accord with those generally applied in gynecologic oncology. In addition, serum
      levels were influenced significantly by menopausal status (except with MCA).

PMID- 8571994
TI  - Efficacy of pelvic floor muscle exercises in women with stress, urge, and mixed
      urinary incontinence.
AB  - OBJECTIVES: Our purpose was (1) to evaluate the efficacy on an intent-to-treat
      basis of a 3-month course of pelvic floor muscle exercises as first-line therapy
      for urinary incontinence in consecutive women seen in a tertiary care center with
      stress, urge, and mixed urinary incontinence and (2) to evaluate whether a
      specially designed audiotape improves compliance and efficacy of the exercises.
      STUDY DESIGN: A prospective randomized trial wa conducted with 71 women seen for
      treatment of urinary incontinence in two tertiary care center referral clinics
      (in the departments of gynecology and urology). The primary outcome measure was
      the number of incontinent episodes, as documented with a 3-day voiding diary.
      Statistical analysis included t tests and Wilcoxon signed-ranks test, as
      appropriate. A value of p < or = 0.05 was considered significant. RESULTS: Forty
      four percent of all enrollees had a > or = 50% improvement in the number of
      incontinent episodes per day. This increased to 56% of enrolles who completed the
      treatment course. For all enrollees the mean number of incontinent episodes per
      day decreased from 2.6 to 1.7 for genuine stress incontinence, from 3.5 to 2.3
      for detrusor instability, and from 3.9 to 3.2 for mixed incontinence. For
      enrollees who completed the 3-month course the mean number of incontinent
      episodes per day decreased from 2.5 to 1.4 for genuine stress incontinence, from
      2.8 to 0.5 for detrusor instability, and from 3.0 to 1.7 for mixed incontinence.
      Six months after completing the course of exercises approximately one third of
      all enrollees reported that they continued to note good or excellent improvement
      and desired no further treatment. There was no difference in outcome measures and
      no difference in compliance between the women who exercised with the aid of the
      audiotape and those who exercised according to our usual office routine (p >
      0.05). CONCLUSIONS: One third of all participants remained improved to the
      patient's satisfaction 6 months after completion of a risk-free, inexpensive,
      simply provided therapy. Our audiotape did not improve our success rate or
      decrease the dropout rate. In this study the exercises were equally effective for
      all three urodynamic diagnoses. Inexpensive methods that could be used by primary
      care providers to improve the success rate of this therapy merits further
      attention.

PMID- 8571993
TI  - Douching and sexually transmitted diseases in pregnant women in Surabaya,
      Indonesia.
AB  - OBJECTIVE: Our purpose was to investigate the association between douching
      (douching agents and timing) and sexually transmitted disease. STUDY DESIGN: A
      cross-sectional survey of sexually transmitted diseases and habits of vaginal
      douching was performed on 599 pregnant women who visited a prenatal clinic in
      Surabaya, Indonesia. RESULTS: Of the 599 pregnant women, 115 (19.2%) had at least
      one sexually transmitted disease (gonorrhea, chlamydia, syphilis, trichomoniasis,
      or herpes simplex virus-2). Most women had douched with water (19%) or water and
      soap (63%) at least once in the preceding month. Approximately 10% of the women
      had douched in the preceding month with a commercial agent (2%) or betel leaf
      (8%). Douching with water alone after sex was not associated with sexually
      transmitted disease. Douching with water and soap or with a betel leaf or
      commercial agent after sex was associated with sexually transmitted disease;
      adjusted odds ratios were 2.6 (95% confidence interval 1.0 to 7.1) and 2.7 (95%
      confidence interval 0.5 to 14.5), respectively. The association was enhanced if
      the women douched before sex or both before and after sex; adjusted odds ratio
      were 2.7 (95% confidence interval 1.0 to 7.3) for douching with water and soap
      and 5.2 (95% confidence interval 1.6 to 16.7) for douching with betel leaf or a
      commercial agent. Compared with women who never douched, women who always douched
      with betel leaf or a commercial agent had a substantially increased risk for
      sexually transmitted disease (adjusted odds ratio 9.4, 95% confidence interval
      1.8 to 50.3). CONCLUSIONS: We found a significant association between sexually
      transmitted disease and douching habits (douching with betel leaf, commercial
      agents, or water and soap). However, further prospective investigations are
      needed to evaluate the temporal relationship between douching and sexually
      transmitted disease.

PMID- 8571995
TI  - Tumor angiogenesis: an independent prognostic parameter in cervical cancer.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the intensity of
      tumor angiogenesis, expressed as microvessel density, is a parameter predicting
      the probability of lymph node metastasis and survival in patients with cervical
      cancer stages IB and IIA. STUDY DESIGN: In a retrospective study of 114 patients
      with cervical cancer stages IB and IIA, microvessel density, lymph node status,
      and several other prognostic parameters were correlated with disease-free
      survival by a multivariate analysis according to Cox proportional-hazards model.
      RESULTS: There was a significant difference in mean microvessel density between
      tumors with and without pelvic lymph node metastasis (p = 0.002). Both
      microvessel density (vessels per square millimeter of stroma). (p = 0.05) and
      pelvic lymph node metastasis (p = 0.007) correlated significantly and
      independently with disease-free survival. CONCLUSION: This study demonstrates
      that microvessel density is an independent prognostic parameter for disease-free
      survival in patients with cervical cancer stages Ib and IIa.

PMID- 8571996
TI  - Pathophysiologic features of a pneumoperitoneum at laparoscopy: a swine model.
AB  - OBJECTIVE: The aim of this study was to examine local and systemic reactions of
      the body to a pneumoperitoneum to elucidate potential dangers and risks of
      laparoscopic procedures. STUDY DESIGN: Laparoscopy was performed on 25 pigs. The
      pigs were divided into five groups by level of intraabdominal pressure (14 and 18
      mm Hg) and gas used (carbon dioxide and air). The effects of the pneumoperitoneum
      on cardiopulmonary condition and the peritoneal milieu were observed. These
      effects should be the result of various changes as the mechanical, ventilatory,
      cellular, hormonal, and immunologic levels. RESULTS: In this animal study marked
      changes in the peritoneal milieu were observed, and we demonstrated that these
      changes were dependent on the gas used, intraabdominal pressure, and duration of
      application. Locally these changes are manifest in the development of severe
      peritoneal acidosis, hypercapnia, and the release of various mediators. Systemic
      changes, in particular cardiopulmonary changes, also depend on the intraabdominal
      pressure and the gas used. CONCLUSION: During conventional pneumoperitoneum the
      peritoneum might change to a large extent so that the development of new risks
      are possibly encouraged. A reduction in intraabdominal pressure with the use of
      carbon dioxide as the insufflation gas should result in normal acid-base balance.

PMID- 8571997
TI  - Ovarian cysts in premenopausal and postmenopausal tamoxifen-treated women with
      breast cancer.
AB  - OBJECTIVE: Our purpose was to investigate the frequency of ovarian cysts in
      tamoxifen-treated breast cancer patients. STUDY DESIGN: The study population
      included 95 consecutive tamoxifen-treated premenopausal and postmenopausal women
      with breast cancer who were followed up by the outpatient clinic at the Hadassah
      University Hospital between September 1990 and June 1992. Tamoxifen was
      administered orally (20 mg/day). All patients underwent a pelvic examination and
      vaginal ultrasonography with a 5 MHz vaginal probe. RESULTS: During the study 11
      of 95 tamoxifen-treated breast cancer patients (11%) had ovarian cysts. Five
      cysts were detected in postmenopausal women (6.3% of the postmenopausal women)
      and six in premenopausal women (37.5% of the premenopausal women). In
      postmenopausal and premenopausal women the mean tamoxifen treatment interval was
      19.4 +/- 7.8 months (range 4 to 48 months) and 28 +/- 6.1 months (range 12 to 54
      months), respectively (p = 0.41). In 8 of the 11 patients the ovarian cystic
      enlargement disappeared after cessation of tamoxifen treatment. Two patients
      underwent laparotomy because of persistent cysts and the third because of a
      rapidly growing myoma. The three cysts were found to be benign. CONCLUSION:
      Ovarian cysts are a common side effect of tamoxifen treatment. The ovarian cysts
      can develop in tamoxifen-treated premenopausal as well as postmenopausal women
      with breast cancer. Most of the tamoxifen-associated cysts disappear after
      tamoxifen treatment is abandoned.

PMID- 8571998
TI  - The role of tumor necrosis factor receptors in tumor necrosis factor-alpha
      mediated cytolysis of ovarian cancer cell lines.
AB  - OBJECTIVE: Our purpose was to define the expression of tumor necrosis factor
      receptors on ovarian cancer cells and determine what role these receptors play in
      tumor necrosis factor-alpha-mediated cytolysis. STUDY DESIGN: Cell surface
      expression of tumor necrosis factor-alpha receptors was determined on ovarian
      cancer cell lines Caov-3, SK-OV-3, NIH:OVCAR-3, and A2780 by a tumor necrosis
      factor-alpha-binding assay that used iodine 125-labeled tumor necrosis factor
      alpha. Monoclonal antibodies specific for the 55 to 60 kd (TR60) and 75 to 80 kd
      (TR80) tumor necrosis factor receptors were used to determine the relative
      density of each receptor type. To elucidate which receptor(s) was responsible for
      mediating the signal for cytolysis, 24-hour MTT cytolytic assays that used tumor
      necrosis factor-alpha and emetine were performed in the presence or absence of
      receptor-specific monoclonal antibodies. RESULTS: The four ovarian cell lines
      expressed a similar number of surface receptors, 4500 to 7000 per cell, had
      similar dissociation constants, 0.3 to 0.6 nmol/L, and expressed predominately
      the TR60 receptor subtype. Receptor function studies showed that the presence of
      the monoclonal antibody to the TR60 receptor completely inhibited tumor necrosis
      factor-alpha-mediated cytolysis, whereas the monoclonal antibody to the TR80
      receptor only partially blocked cytolysis. CONCLUSIONS: Ovarian cancer cell lines
      express both tumor necrosis factor receptors, with the TR60 receptor being the
      dominant subtype. Tumor necrosis factor-alpha-mediated cytolysis appears to be
      dependent on the presence of a functional TR60 receptor. The TR80 receptor does
      not appear requisite for cytolysis; however, a complementary role cannot be
      excluded. Manipulation of tumor necrosis factor receptor subtypes on ovarian
      cancer cells may enhance the cytotoxic effects, thus improving the therapeutic
      efficacy of tumor necrosis factor-alpha.

PMID- 8571999
TI  - Bone-sparing properties of oral contraceptives.
AB  - Postmenopausal osteoporosis is a major health care problem that affects 20
      million women in the United States and accounts for > 1 million fractures per
      year. Hormone replacement therapy is effective for reducing bone loss in the
      postmenopausal women. However, intervention before menopause may delay or prevent
      the decline in bone mass that begins between ages 30 and 40 years. The effects of
      oral contraceptives on bone mass have been investigated, and a positive
      association between oral contraceptive use and bone mass that is directly related
      to the duration of oral contraceptive use was observed. The effects of oral
      contraceptives on bone mass may be related to the specific formation. The effect
      of estrogens is dose related, and the optimal dose appears to be 25 to 35
      micrograms of ethinyl estradiol or its equivalent. Results from several studies
      show that norethindrone has a positive effect on bone mass. An oral contraceptive
      may offer optimal birth control for the older premenopausal woman who currently
      uses other forms of birth control.

PMID- 8572000
TI  - Fluorescence and photosensitization of experimental endometriosis in the rat
      after systemic 5-aminolevulinic acid administration: a potential new approach to
      the diagnosis and treatment of endometriosis.
AB  - OBJECTIVE: Our purpose was to evaluate and compare the conversion of 5
      aminolevulinic acid into the endogenous photosensitizer protoporphyrin IX in
      experimentally induced endometriosis and in other normal tissues in a rat model.
      STUDY DESIGN: Fluorescence of experimental endometriotic lesions, uterus,
      peritoneum, bowel mesentery, bladder, eye, skin, and skeletal muscle was assessed
      3 hours after either intravenous, oral, or intrauterine administration of 5
      aminolevulinic acid with use of spectrophotofluorometry. In another experiment
      the fluorescence of surgically induced endometriosis and adjacent normal
      peritoneum was evaluated every 15 minutes after 5-aminolevulinic acid
      administration to assess the time course of protoporphyrin IX production.
      RESULTS: In the rat endometriosis model intralesional and systemic 5
      aminolevulinic acid produced fluorescence within implants showing viable
      endometrial cells. Treatment with 5-aminolevulinic acid produced low-intensity
      fluorescence in peritoneum, bowel mesentery, and eye. Relatively intense
      fluorescence was seen in skin, bladder, and uterus. No fluorescence was observed
      in skeletal muscle. The intensity of fluorescence varied with the dosage and
      route of administration of 5-aminolevulinic acid. Fluorescence intensity of
      protoporphyrin IX was significantly greater in implants than in adjacent normal
      peritoneum between 2 and 4 hours after treatment. CONCLUSIONS: Protoporphyrin IX
      fluorescence in experimentally induced endometriosis lesions after intravenous
      and oral delivery of 5-aminolevulinic acid was significantly greater than the
      fluorescence detected in adjacent normal peritoneum.

PMID- 8572001
TI  - Growth modulatory effects of granulocyte-macrophage colony-stimulating factor on
      human cell lines derived from gynecologic malignancies.
AB  - OBJECTIVE: In spite of increased expression of granulocyte-macrophage colony
      stimulating factor surface receptors on solid tumors, the growth modulatory
      effects of granulocyte-macrophage colony-stimulating factor have not been well
      defined in gynecologic malignancies. We assessed the in vitro growth effects of
      granulocyte-macrophage colony-stimulating factor on such cell lines. STUDY
      DESIGN: By use of a chromium 51 incorporation assay the in vitro growth effects
      of granulocyte-macrophage colony-stimulating factor on 12 cell lines derived from
      human malignancies were measured. RESULTS: No growth stimulatory or inhibitory
      effect was mediated by granulocyte-macrophage colony-stimulating factor on six
      cell lines, whereas three lines showed consistent but not statistically
      significant dose-dependent growth stimulation. There was, however, a
      statistically significant increase in growth of short duration in three other
      cell lines at clinically relevant doses of granulocyte-macrophage colony
      stimulating factor. Fluorometric cell cycle analysis demonstrated no change in
      cell-cycle distribution. CONCLUSION: Within this in vitro system, stimulation of
      gynecologic malignancies in patients receiving granulocyte-macrophage colony
      stimulating factor for mitigation of the myelosuppressive effects of cytotoxic
      chemotherapy does not appear to be widespread nor sustained beyond 48 hours.

PMID- 8572003
TI  - Ultrastructure of the microvasculature in human endometrial hyperplasia.
AB  - OBJECTIVE: Our purpose was to determine the effect of hyperplasia on cell-to-cell
      communication in the microvasculature of the human endometrium. STUDY DESIGN: Ten
      biopsy specimens of simple and complex hyperplasia of the human endometrium were
      investigated by electron microscopy. RESULTS: The microvasculature of the
      hyperplastic endometrium shows morphologic disorder. The extracellular matrix is
      altered, and cell death is widespread. Intercellular contact is infrequent or
      absent. CONCLUSIONS: These results are in marked contrast to the ultrastructure
      of the normal microvasculature. The complex cell-to-cell interaction observed in
      normal tissue appears lost. This report, combined with others, indicates that
      cell-to-cell contact is sparse in hyperplastic endometrium.

PMID- 8572002
TI  - Ethically justified clinically comprehensive guidelines for the management of the
      depressed pregnant patient.
AB  - OBJECTIVE: This article proposes ethically justified clinical guidelines for
      managing depressed patients during pregnancy. STUDY DESIGN: We reviewed
      literature on depression and its consequences for pregnancy and related that
      literature to ethical principles. RESULTS: The health effects of depression on
      the pregnant woman and her fetus cannot be managed without consideration of the
      chronic and variable impairment of autonomy that may result from the effects of
      depression on the pregnant woman's decision-making capacity. CONCLUSION: When the
      fetus is previable, recommendations concerning the disposition and prenatal
      diagnosis of the pregnancy should be nondirective, whereas strong treatment
      recommendations are justifiable if the pregnant woman has decided to continue her
      pregnancy and is severely depressed. After viability, directive counseling for
      fetal benefit is ethically justified. The guidelines focus on preventive ethics
      strategies to enhance the decision-making capacity of the depressed pregnant
      patient.

PMID- 8572004
TI  - Decreasing the cesarean section rate in a private hospital: success without
      mandated clinical changes.
AB  - OBJECTIVE: We analyzed the delivery statistics from our institution to describe a
      successful program of cesarean section delivery reduction and to help us
      understand what factors explained the reduction. STUDY DESIGN: A retrospective
      analysis of various cesarean section rates and risk factors from a prospectively
      collected delivery database of all patients delivered between May 15, 1988, and
      June 30, 1994. During the study period we instituted a program of increasing
      awareness, confidential provider feedback, more aggressive laboring techniques,
      and other clinical guidelines. The delivery data were divided into 6-month
      intervals and analyzed by chi 2 tables. RESULTS: The overall cesarean section
      rate fell from 31.1% to 15.4%. Similar reductions were noted in the primary
      (17.9% to 9.8%) and repeat cesarean section rates (13.2% to 5.7%). The primary
      cesarean section rate fall was accompanied by a drop in abdominal delivery for
      cephalopelvic disproportion and fetal distress. The repeat cesarean section rate
      is explained by a significant increase in trial and successful vaginal birth
      after cesarean delivery. No increase in maternal, fetal, or neonatal morbidity or
      mortality was observed. CONCLUSIONS: We have demonstrated that the cesarean
      delivery rate can be safely lowered in a private hospital without mandated
      clinical changes. Our data suggest that careful and detailed feedback can lead to
      improved clinical practice.

PMID- 8572005
TI  - Predictive score for vaginal birth after cesarean section.
AB  - OBJECTIVE: Our purpose was to evaluate the relative weight of the different
      variables that may influence the chances of vaginal birth after one cesarean
      delivery, with the aim of developing a predictive score for success of such a
      trial. STUDY DESIGN: In this retrospective study, which covered a 10-year period
      (1981 to 1990), 471 women who attempted vaginal birth at a level III university
      hospital after one abdominal delivery were studied as to the subsequent delivery
      outcome. An attempt to identify possible prognostic factors for success of such a
      trial was made. RESULTS: A trial of labor was successful in 368 (78.1%) of women
      and 103 (21.9%) had a repeat cesarean section. Variables of significant
      predictive value were vaginal birth before cesarean section (odds ratio 1.8),
      malpresentation (odds ratio 1.9), pregnancy-induced hypertension (odds ratio
      2.3), and Bishop score > or = 4 (odds ratio 6.0). Cephalopelvic disproportion and
      failure to progress did not demonstrate a significant predictive value (odds
      ratio 0.81) for success or failure in subsequent delivery. In fact, 63.8% of
      women with this indication have successfully undergone vaginal delivery. Maternal
      age (odds ratio 0.9) had no bearing on vaginal delivery success rates, whereas
      both macrosomia (odds ratio 0.2) and intrauterine growth retardation tended to
      decrease the chances for vaginal birth after cesarean section. CONCLUSIONS: A
      trial of labor after one cesarean section should be encouraged in most women who
      are willing to attempt it, provided no obstetric contraindication exists. A
      scoring system that may help to identify women with a greater chance for vaginal
      delivery is proposed.

PMID- 8572006
TI  - Using the medical audit cycle to reduce cesarean section rates.
AB  - OBJECTIVE: Our purpose was to determine whether completion of the medical audit
      cycle in labor ward practice could safely reduce cesarean section rates. STUDY
      DESIGN: A retrospective medical audit of all deliveries from 1984 to 1988 was
      performed. The groups of women contributing most to the overall cesarean section
      rate were identified. Strategies for labor management directed at the primary
      indication for cesarean section (dystocia) were developed and introduced. The
      effect was monitored prospectively from 1989 through 1992. Data were analyzed
      with the chi 2 test. RESULTS: A total of 21,125 deliveries were studied. After
      management change the overall cesarean section rate was decreased (9.5% vs 12%, p
      < 0.0001). In our population spontaneously laboring nulliparous women with a
      singleton, cephalic, term pregnancy contributed a significant number of cesarean
      sections 1982 to 1988 (19.7% of all cesarean sections). Applying principles of
      early diagnosis and treatment of dystocia in these women resulted in a decrease
      in the cesarean section rate (2.4% vs 7.5%, p < 0.0001). This was primarily
      responsible for the overall decrease in the cesarean section rate. CONCLUSION:
      Effective medical audit of labor management can reduce cesarean section rates.

PMID- 8572007
TI  - Randomized investigation of antimicrobials for the prevention of preterm birth.
AB  - OBJECTIVE: Occult amniotic fluid infection has emerged as a possible cause of
      many heretofore unexplained preterm births. We sought to determine whether
      antimicrobial therapy is effective in preventing preterm delivery. STUDY DESIGN:
      A double-blind, placebo-controlled, randomized trial was conducted to study the
      efficacy of ampicillin-sulbactam and amoxicillin-clavulanic acid in women
      hospitalized for preterm labor between 24 and 34 weeks' gestation. During this
      investigation no tocolytics or steroids were used. RESULTS: Thirty-nine women
      with preterm labor received antimicrobial therapy and 39 received placebos. The
      mean gestational ages at study entry were 29.8 +/- 0.4 weeks (SEM) and 30.6 +/-
      0.3 weeks in the antimicrobial and placebo groups, respectively (not
      significant). Similarly, the mean gestational ages at delivery were 34.2 +/- 0.7
      and 34.1 +/- 0.6 weeks, respectively (not significant). Other index values of
      pregnancy outcome, for example, birth weight, neonatal morbidity, and prenatal
      death, were not significantly improved by antimicrobial therapy given to the
      mother in preterm labor. CONCLUSION: We find that antimicrobial therapy given to
      women in preterm labor is ineffective in the prevention of preterm birth.

PMID- 8572008
TI  - Diagnosis and treatment of drug and alcohol abuse in women.
AB  - The major reasons why women abuse drugs and alcohol are presented with a focus on
      societal and psychologic bases. A structured format is provided for eliciting a
      history while motivating the patient to obtain adequate treatment. A workable
      treatment contract is presented. A three-stage method of treatment is described,
      which focuses on the following: (1) achieving abstinence, (2) maintaining
      abstinence, and (3) achieving sobriety (advanced recovery).

PMID- 8572009
TI  - Disseminated intravascular coagulation and antithrombin III depression in acute
      fatty liver of pregnancy.
AB  - OBJECTIVE: Acute fatty liver of pregnancy has been associated with a syndrome of
      marked depression of antithrombin III and disseminated intravascular coagulation.
      We sought to identify the clinical importance of this accelerated coagulation.
      STUDY DESIGN: The medical records of patients with acute fatty liver of pregnancy
      identified during the period of 1982 to 1994 were retrospectively reviewed.
      RESULTS: Twenty-eight patients with acute fatty liver of pregnancy were
      identified for an incidence of 1:6692 births. Laboratory evidence of persistent
      disseminated intravascular coagulation was found in all patients tested. Six
      patients had clinical bleeding, all associated with genital tract injury. Twenty
      three of twenty-three patients tested had markedly decreased antithrombin III
      levels (average 11%, normal range 80% to 100%). Seven patients received
      antithrombin III transfusions, which was associated with a significant transient
      rise in the plasma level. Compared with patients not transfused, however, there
      was a similar clinical outcome. CONCLUSION: Profoundly depressed antithrombin III
      levels and laboratory evidence of disseminated intravascular coagulation were
      present in all cases of acute fatty liver of pregnancy but rarely influenced
      clinical outcome unless there was concomitant genital tract injury. Antithrombin
      III transfusions increased plasma levels, but no definite clinical benefit was
      established in this series because of the small number of cases.

PMID- 8572010
TI  - Is manual palpation of uterine contractions accurate?
AB  - OBJECTIVE: The aims of this study were to assess the accuracy of uterine
      contraction palpation, determine whether the accuracy of palpation improves with
      experience, determine clinical factors that affect the accuracy of palpation, and
      evaluate the range of intrauterine pressure present when an observer notes the
      contraction to be mild, moderate, or strong. STUDY DESIGN: A total of 236
      observations were obtained by use of intrauterine pressure catheters on 46
      laboring patients in the first stage of labor. The blinded observers (obstetrics
      and gynecology residents, maternal-fetal medicine fellows and faculty, and labor
      and delivery nurses) were asked to label a contraction as mild, moderate, or
      strong. Patient's height, weight, parity, and gestational age, use of oxytocin,
      use of epidural anesthesia, and laboring position, and the level of training of
      the observer were noted. RESULTS: Mild, moderate, and strong contractions had
      intrauterine pressures of 35.2 +/- 33.8 mm Hg (+/- 2 SD), 44.9 +/- 35.4 mm Hg,
      and 55.5 +/- 28.0 mm Hg, respectively. The observers were accurate in predicting
      contraction strength 49% of the time. There was no improvement in accuracy with
      increased physician experience. All physicians as a group were more accurate than
      nurses (p < 0.05). Accuracy was not affected by clinical variables. CONCLUSION:
      Manual palpation of uterine contractions is an inaccurate means of determining
      contraction strength.

PMID- 8572011
TI  - Content of prenatal care during the initial workup.
AB  - OBJECTIVE: In its landmark document Caring for Our Future: The Content of
      Prenatal Care, the Public Health Service Expert Panel on the Content of Prenatal
      Care presented a framework for refocusing prenatal care in the 1990s. The purpose
      of this study was to examine the extent to which the panel's recommendations for
      preconceptional care and for the content of the initial prenatal workup were
      followed 3 years after they were issued. STUDY DESIGN: A retrospective review of
      the prenatal records of 147 patients in Durham and Chatham counties, North
      Carolina, was conducted. Providers were selected at random, and their first 10
      new prenatal patients were enrolled in the study. Data were analyzed
      descriptively to characterize patterns in content of care and, with multiple
      logistic regression analysis, to determine whether there were relationships
      between selected maternal characteristics and receipt of selected components of
      care. RESULTS: Only 11% of the patients had one or more preconceptional visits.
      During the initial prenatal workup risk assessment through history taking and
      physical examination was virtually complete, whereas documentation of laboratory
      tests varied. Only about half the population received routine counseling on
      pregnancy and health behaviors. Multiple logistic regression analysis revealed a
      consistent association between initiating prenatal care early in pregnancy and
      receipt of most laboratory tests. No other consistent relationships were found.
      CONCLUSIONS: This study suggests that adherence to such long-standing prenatal
      care practices as physical examination, history taking, and some laboratory tests
      was high. But the components of prenatal care recommended by the expert panel to
      ensure behavioral risk assessments and health promotion and education early in
      pregnancy were provided at lower and more variable rates. Use of preconceptional
      care was also low. Further research into the use and content of care before and
      during pregnancy is required to understand variations in practice patterns and
      levels of adherence to recommendations on the content of care.

PMID- 8572012
TI  - The effect of ovulation induction on the concentration of maternal serum relaxin
      in twin pregnancies.
AB  - OBJECTIVE: Our purpose was to determine the effects of fetal number, various
      ovulation induction treatments, and placental hormones on the concentration of
      maternal serum relaxin. STUDY DESIGN: The concentrations of relaxin, human
      chorionic gonadotropin, estriol, and alpha-fetoprotein were determined in blood
      samples drawn at 16 to 18 weeks for prenatal diagnosis in 72 singleton and 115
      twin pregnancies and analyzed by one-way analysis of variance, correlation
      analysis, and stepwise multiple linear regression of the log-transformed data.
      RESULTS: The maternal serum concentrations of each of the four measured hormones
      were significantly higher in the twin pregnancies than in the singleton
      pregnancies: 1.4-fold for relaxin, 1.9-fold for human chorionic gonadotropin, 1.9
      fold for estriol, and 2.2-fold for alpha-fetoprotein (all p < 0.01). The
      concentrations of each of the four hormones were significantly correlated with
      each of the others and with the number of fetuses (p < 0.01), except that estriol
      was not significantly correlated with human chorionic gonadotropin. The serum
      relaxin concentration in twin pregnancies after treatment with follicle
      stimulating hormone and luteinizing hormone (menotropins) (n = 10) was 3.3-fold
      that in twins resulting from spontaneous ovulation (n = 89, p < 0.01). In twins
      resulting from in vitro fertilization or gamete intrafallopian transfer (n = 9)
      the serum relaxin concentration was 2.6-fold higher than in twins resulting from
      spontaneous ovulation (p < 0.01). The effect of clomiphene citrate (1.2-fold, n =
      7) failed to reach statistical significance. CONCLUSIONS: The second fetus causes
      a 1.4-fold increase in the concentration of maternal serum relaxin in twin
      pregnancies. Induction of ovulation with menotropins causes an additional 3.3
      fold increase, whereas in vitro fertilization or gamete intrafallopian transfer
      treatment causes an additional 2.6-fold increase over that seen in twin
      pregnancies that followed spontaneous ovulation.

PMID- 8572013
TI  - Relaxin secretion in in vitro fertilization pregnancies.
AB  - OBJECTIVE: This study was designed to determine whether the late luteal
      functional status of the corpora lutea in in vitro fertilization cycles alters
      the secretion of relaxin during pregnancy. STUDY DESIGN: Analysis of serum
      relaxin, human chorionic gonadotropin, and steroid concentrations in sera of
      women with pregnancies viable beyond the twelfth week as a result of in vitro
      fertilization treatment was performed. RESULTS: The serum estradiol and
      progesterone concentrations decreased 5.5- and 4-fold from days 5 to 6 after
      human chorionic gonadotropin to days 11 to 13 after human chorionic gonadotropin,
      respectively. The serum relaxin concentration increased 8-fold between the 11- to
      15-day interval and the 16- to 50-day interval after human chorionic gonadotropin
      and another 6-fold to the 51- to 90-day interval after human chorionic
      gonadotropin (all p < 0.01). Multiple linear regression analysis showed that the
      serum estradiol level 11 to 13 days after human chorionic gonadotropin and the
      serum human chorionic gonadotropin level 11 to 15 days after human chorionic
      gonadotropin were the most powerful paired predictors of the concentration of
      serum relaxin measured in the 11- to 15-day interval after human chorionic
      gonadotropin interval (R2 = 0.39, n = 50), the 16- to 50-day interval (R2 = 0.61,
      n = 51), and the 51- to 90-day interval (R2 = 0.55, n = 39). CONCLUSION:
      Secretion of relaxin is determined by an interaction of the late luteal
      functional status of the corpora lutea and the human chorionic gonadotropin
      secreted by the implanting pregnancy. These data allow for the hypothesis that
      inducing functional luteolysis by substituting one or more injections of
      luteinizing hormone for the human chorionic gonadotropin injection may decrease
      secretion of steroids, relaxin, and other factors from the corpora lutea during
      pregnancy, decreasing the risk of premature delivery in multiple gestations and
      the ovarian hyperstimulation syndrome.

PMID- 8572014
TI  - Congenital cytomegalovirus infection: a long-standing problem still seeking a
      solution.
AB  - OBJECTIVE: The purpose of this study was to review the accuracy of current tests
      used for the diagnosis of in utero cytomegalovirus infection and to discuss the
      potential value of preconceptional and postconceptional screening programs for
      prevention of congenital infection. STUDY DESIGN: A computer-assisted search was
      performed for relevant English language publications between 1987 and 1994. We
      identified 119 cases of suspected intrauterine cytomegalovirus infection in which
      either amniotic fluid or fetal blood had been analyzed antenatally. RESULTS:
      Congenital cytomegalovirus infection affects 0.5% to 2.5% of all newborns. The
      rate of transmission to the fetus after primary infection during pregnancy ranges
      from 15% to 50%. Of the fetuses infected in utero, 10% exhibit congenital
      cytomegalovirus syndrome. Evaluation of 119 cases of suspected infection has
      shown that polymerase chain reaction and cultures of amniotic fluid are the most
      reliable tests for prenatally determining the presence of viral particles.
      However, efficacy of routine antenatal screening in reducing the rate of fetal
      disease is limited. CONCLUSION: It is concluded that at present the accuracy of
      tests used for the diagnosis of in utero cytomegalovirus infection is
      undetermined. Serologic screening of all pregnant women is of limited value and
      at present is not recommended.

PMID- 8572015
TI  - Effects of estradiol-17 beta and progesterone on isolated human omental artery
      from premenopausal nonpregnant women and from normotensive and preeclamptic
      pregnant women.
AB  - OBJECTIVE: Our purpose was to study the direct vascular effects of estradiol-17
      beta and progesterone on isolated omental artery from premenopausal nonpregnant
      women and from normotensive and preeclamptic pregnant women. STUDY DESIGN:
      Omental artery rings from normotensive premenopausal nonpregnant women and from
      normal and preeclamptic pregnant women were mounted in Krebs-bicarbonate solution
      in organ baths for isometric tension recording. The endothelium was removed from
      some of the rings, and all were contracted with potassium chloride (60 mmol/L)
      and then exposed to cumulative concentrations of estradiol-17 beta and
      progesterone. Concentration response curves were constructed and relaxation was
      expressed as percent change from the reference 60 mmol/L potassium chloride
      contraction. Data analysis was by repeated-measures analysis of variance, Newman
      Keuls test, and the unpaired Student t test as appropriate. A two-tailed p < 0.05
      was considered statistically significant. RESULTS: Both hormones studied caused
      vasorelaxation in omental arteries from all three groups of patients. Of the two,
      estradiol-17 beta was more effective, regardless of the presence or absence of
      endothelium. Removal of the endothelium shifted the estradiol-17 beta
      concentration-response curve to the right in the normal pregnant artery but not
      in nonpregnant or preeclamptic vessels. Removal of the endothelium shifted the
      progesterone concentration-response curve to the left in arteries from
      preeclamptic patients. CONCLUSIONS: Estradiol-17 beta and progesterone have
      direct in vitro vasodilator activity that appears to be linked, in part, to the
      endothelium in human omental artery from normal and hypertensive women in
      different hormonal states.

PMID- 8572016
TI  - A critique of the new recommendations for weight gain in pregnancy.
AB  - Recent Institute of Medicine recommendations for weight gain in pregnancy
      advocate a marked increase over prior guidelines, and for reasons that must be
      questioned. The objectives of these new guidelines are to reduce perinatal
      mortality, prematurity, and fetal growth retardation. Evidence of a causal
      relationship between less maternal weight gain and these adverse outcomes is
      lacking. In addition, the consequences of increased pregnancy weight gain have
      been incompletely assessed. The risk-to-benefit ratio may be prohibitive. The new
      recommendations, which will be considered by many to be clinical guidelines, fall
      short of the formulation criteria recommended by the United States Preventive
      Services Task Force.

PMID- 8572017
TI  - Diurnal variation in angiotensin sensitivity in pregnancy.
AB  - OBJECTIVE: Our purpose was to study the diurnal variation in angiotensin II
      sensitivity. STUDY DESIGN: Angiotensin sensitivity tests were performed at 9 AM
      and at 2 PM in 12 normotensive pregnant women, with each woman serving as her own
      control. RESULTS: In all patients the effective pressor dose was higher in the
      afternoon. CONCLUSION: We suggest the greater sensitivity to angiotensin in the
      morning is related to an intrinsic circadian variation in vascular reactivity.
      When the result of an angiotensin sensitivity test is interpreted, the time of
      day it is performed should be taken into account.

PMID- 8572018
TI  - The presence of fetal fibronectin in the cervicovaginal secretions of women at
      term--its role in the assessment of women before labor induction and in the
      investigation of the physiologic mechanisms of labor.
AB  - OBJECTIVE: Our purpose was to determine whether the presence of fetal fibronectin
      in cervicovaginal secretions of patients undergoing induction of labor reflected
      the cervical state and ultimately the ease of induction of labor. STUDY DESIGN: A
      prospective observational study of 103 patients undergoing induction of labor at
      term was conducted at Liverpool Maternity Hospital, a large university teaching
      hospital. We studied the women after 37 completed weeks of pregnancy. A Dacron
      (Adeza Biomedical, Sunnyvale, Calif.) polyester swab specimen was first taken
      from the endocervix for assessment of the presence of the fetal fibronectin. The
      cervix was then assessed by digital vaginal examination and scored with a
      modified Bishop's score. The fetal fibronectin swab was processed at the bedside
      with a membrane immunoassay kit specific for fetal fibronectin. A score was
      ascribed depending on the strength of the fibronectin reaction determined by the
      intensity of the color change on the plate, the presence of fetal fibronectin
      resulting in a score of 1 to 4. The patient was subsequently managed according to
      the standard induction protocol of the unit. The clinicians involved in the
      patient's care were blind to the result of the fetal fibronectin swab. RESULTS:
      There was a good correlation between the modified Bishop's score and the fetal
      fibronectin score (r = 0.58, p < 0.001). To predict a latent phase of < 8 hours,
      a fetal fibronectin score of 3 or 4 has a sensitivity of 73% with a specificity
      of 83% and a modified Bishop score of > or = 4 has a sensitivity of 75% and a
      specificity of 73%. For delivery within 12 hours of induction of labor a fetal
      fibronectin score of > or = 3 has a sensitivity of 61% and specificity of 83%
      compared with the modified Bishop score of > or = 4, which has a sensitivity of
      76% and a specificity of 72.5%. CONCLUSIONS: The fetal fibronectin score is as
      good as the modified Bishop score as an index of the ease with which induction of
      labor may be performed. This would imply that it also reflects the proximity of
      the onset of labor. The presence of fetal fibronectin cervicovaginal secretions
      is therefore a marker of the changes in the cervix and membranes that precede
      labor regardless of the gestational age.

PMID- 8572019
TI  - The relationship between uterine artery Doppler velocimetry and umbilical venous
      adenosine levels in pregnancies complicated by preeclampsia.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationship between
      uteroplacental circulatory insufficiency and the fetoplacental release of
      adenosine in pregnancies complicated by preeclampsia. STUDY DESIGN: We performed
      uterine artery Doppler velocimetry and calculated the pulsatility index of the
      uterine artery, to detect uteroplacental circulatory insufficiency, immediately
      before cordocentesis in 39 pregnant women complicated by preeclampsia. Umbilical
      venous blood obtained by cordocentesis was then analyzed for blood gases, pH, and
      plasma adenosine levels. Increased plasma adenosine was taken to signal its
      increased release from the placenta and fetus relative to its rate of
      disappearance. RESULTS: The mean umbilical venous plasma adenosine level in the
      abnormal pulsatility index group was 1.78 +/- 0.17 mumol/L (mean +/- SEM, n =
      25), significantly higher than in the normal pulsatility index group 0.58 +/-
      0.14 mumol/L (n = 14, p < 0.001). Furthermore, in the abnormal pulsatility index
      group the elevation of plasma adenosine levels in the umbilical vein was found
      even in normoxic fetuses. CONCLUSION: Fetal plasma adenosine increases before
      uteroplacental circulatory insufficiency becomes severe enough to cause
      generalized fetal hypoxemia. We postulate that enhanced adenosine formation in
      the fetus, umbilical cord vessels, and particularly the placenta may, at least in
      part, contribute to control and maintenance of placental blood flow.

PMID- 8572020
TI  - Plasma P selectin (GMP-140) and glycocalicin are elevated in preeclampsia and
      eclampsia: their significances.
AB  - OBJECTIVE: We measured the concentrations of plasma P selectin (or GMP-140) and
      glycocalicin in preeclamptic and eclamptic women. Correlations between these two
      parameters and blood pressures, platelet counts, or plasma thrombin-antithrombin
      complex values were evaluated. STUDY DESIGN: By use of enzyme-linked
      immunosorbent assays we measured the plasma GMP-140 and glycocalicin levels in
      normal pregnancies (n = 10) and preeclamptic (n = 10) and eclamptic (n = 20)
      pregnancies. The glycocalicin index was calculated as follows: (glycocalicin x
      [250 x 10(6)/ml])/(Individual platelet counts). Correlations between plasma GMP
      140, glycocalicin, glycocalicin index values, blood pressures, platelet counts,
      and plasma thrombin-antithrombin complex values were analyzed. RESULTS: Plasma
      GMP-140 levels were found to be significantly elevated in preeclamptic (p <
      0.0005) and eclamptic cases (p < 0.0001) compared with normotensive controls.
      Plasma glycocalicin (p = 0.01, 0.007) and glycocalicin index (p = 0.005, 0.002)
      values were also markedly elevated in preeclamptic and eclamptic patients
      compared with normal pregnant patients. Significant correlations between platelet
      counts or plasma thrombin-antithrombin complex levels and their corresponding
      plasma GMP-140 and glycocalicin and glycocalicin index values have been found in
      preeclamptic and eclamptic cases. However, blood pressures had correlations with
      GMP-140, glycocalicin, and glycocalicin index values in eclamptic cases.
      CONCLUSIONS: We demonstrated an elevation of plasma GMP-140 and platelet
      glycocalicin in preeclampsia and eclampsia. This study also reflects the
      usefulness of glycocalicin as a marker of platelet activation or turnover and
      endothelial dysfunction in these diseases.

PMID- 8572021
TI  - Estimating the date of confinement: ultrasonographic biometry versus certain
      menstrual dates.
AB  - OBJECTIVE: Our purpose was to evaluate the clinical implications of current
      pregnancy dating policies in a population where routine ultrasonography is
      performed in the first half of pregnancy. STUDY DESIGN: A total of 34,249
      computer files of singleton pregnancies that had both "certain" menstrual dates
      and ultrasonographic biometry were retrieved from the East Midlands Obstetric
      Database. The estimated dates of delivery were calculated by five different
      methods: menstrual dates alone, ultrasonography alone, or a combination of both
      with menstrual dates used if the discrepancy with the ultrasonography dates was
      within 7, 10, or 14 days, respectively. The accuracy of each method in predicting
      the actual date of delivery was calculated. Differences among methods were
      evaluated with nonparametric tests. RESULTS: Compared with use of certain
      menstrual dates, ultrasonographic dating led to a 70% reduction in the number of
      pregnancies considered postterm. Delivery occurred within +/- 7 days of the
      estimated date of confinement in 49.5% cases when menstrual dates alone were used
      and in 55.2% if ultrasonography alone was used; for +/- 10 days, the
      corresponding figures were 64.1% and 70.3%. Scan dating alone was significantly
      better in predicting the actual date of delivery than any of the dating policies
      taking menstrual dates alone or in combination with ultrasonography. CONCLUSIONS:
      Even if menstrual dates are considered "certain," there is no advantage in taking
      them into consideration for calculating the expected date of delivery if a dating
      ultrasonography result is available. Dating by ultrasonographic biometry in the
      first half of pregnancy results in a more accurate prediction of the delivery
      date than using menstrual data alone or in combination with ultrasonography.

PMID- 8572022
TI  - A population-based case-control study of risk factors for breech presentation.
AB  - OBJECTIVE: We evaluated relationships between breech presentation and infant,
      maternal, and pregnancy characteristics of singleton births. STUDY DESIGN: A
      population-based case-control study (3588 breech cases, 8183 controls) was
      conducted with data from the 1987 to 1988 Washington State birth certificate.
      RESULTS: Low birth weight, short gestational age, primiparity, and older maternal
      age were associated with increased risk of breech birth, and after we controlled
      for these factors, the following were also associated with breech birth:
      hydrocephalus, established maternal diabetes, congenital malformation of the
      infant, smoking during pregnancy, and late or no prenatal care. In addition,
      black and Filipino women had decreased risk of breech presentation compared with
      white women. CONCLUSION: Several different maternal and infant characteristics
      appear to increase risk of breech birth, suggesting that there may be several
      different biologic mechanisms leading to breech presentation.

PMID- 8572023
TI  - Immune interferon gamma inhibits translational mobility of a plasma membrane
      protein in preimplantation stage mouse embryos: a T-helper 1 mechanism for
      immunologic reproductive failure.
AB  - OBJECTIVE: Immune interferon gamma adversely affects mouse embryo development and
      has been proposed as a mediator of reproductive failure involving T-helper 1
      immunity. We hypothesized that one mechanism by which interferon gamma could
      exert an adverse effect on embryos was by altering plasma membrane organization
      and transmembrane protein mobility. STUDY DESIGN: The fluorescence photobleaching
      recovery technique was used to measure the effect of the T-helper 1 cytokine
      interferon gamma on the translational mobility of a specific embryonic surface
      glycoprotein recognized by the monoclonal antibody S75. RESULTS: Compared with
      controls interferon gamma significantly decreased the fractional mobility of
      fluorescein isothiocyanate S75 in one- and two-cell mouse embryos. CONCLUSION:
      Interferon gamma may alter plasma membrane domains or cytoskeletal organization
      in early-stage embryos. By restricting plasma membrane protein mobility
      interferon gamma could effect T-helper 1-mediated reproductive failure.

PMID- 8572024
TI  - Hyperuricemia and xanthine oxidase in preeclampsia, revisited.
AB  - Hyperuricemia is associated with the severity of preeclampsia and with fetal
      outcome. Traditionally the high uric acid concentration in preeclampsia has been
      attributed soley to renal dysfunction. Preeclampsia is also characterized by
      increased free radical formation and elevated oxidative stress. Xanthine
      dehydrogenase/oxidase produces uric acid. Xanthine dehydrogenase/oxidase is
      present as two isoforms in vivo. Uric acid production is coupled with formation
      of reactive oxygen species when the enzyme is in the oxidase form. Several
      factors can increase the holoenzyme activity and the conversion of xanthine
      dehydrogenase/oxidase to its oxidase form. These factors include hypoxia
      reperfusion, cytokines, and increased substrate availability (xanthine and
      hypoxanthine). Preeclampsia is characterized by hyperuricemia and signs of
      increased formation of reactive oxygen species and decreased levels of
      antioxidants. Preeclampsia is also characterized by shallow implantation,
      producing a relatively hypoxic maternal-fetal interface, and increased turnover
      of trophoblast tissue, which can result in higher xanthine and hypoxanthine
      concentrations and higher levels of circulating cytokines. These mechanisms can
      lead to increased production of uric acid and free radicals and contribute to the
      hyperuricemia and increased oxidative stress present in preeclampsia.

PMID- 8572025
TI  - De formato foetu liber singulairs, aeneis figuris exornatus...

PMID- 8572026
TI  - Nausea after endometrial resection.

PMID- 8572027
TI  - Fluid absorption during operative hysteroscopy: incidence, prevention,
      monitoring?

PMID- 8572028
TI  - Primary abdominal pregnancy: disregarding clinical features leads to
      misdiagnosis.

PMID- 8572029
TI  - Low or high doses of spironolactone for treatment of maternal Bartter's syndrome.

PMID- 8572030
TI  - How frequently should the amniotic fluid index be performed during the course of
      antepartum testing?
AB  - OBJECTIVE: Our purpose was to evaluate the need for frequent amniotic fluid
      volume assessments in our antepartum testing unit. STUDY DESIGN: In a
      retrospective analysis of data accumulated over 1 year in our antepartum testing
      unit amniotic fluid index values performed at 3- to 4-day intervals were compared
      with follow-up values. Of 11,827 amniotic fluid index values, there were 6291
      with follow-up values within 4 days. The results were stratified on the basis of
      the subsequent amniotic fluid index value and estimated gestational age.
      Comparisons were made relating to amniotic fluid index testing intervals of 4
      versus 7 days. RESULTS: Patients with an amniotic fluid index > 8 cm had a 2.3%
      chance (128/5677) of having oligohydramnios (amniotic fluid index < or = 5.0 cm)
      in the next 4 days. Those patients with low-normal amniotic fluid index values (5
      to 8 cm) had a 16.2% chance (96/593) of having oligohydramnios in the next 4
      days. There were few patients with an amniotic fluid index < or = 5 cm who had
      subsequent amniotic fluid index values measured. Patients with an amniotic fluid
      index > 8 cm had a 2.2% chance (156/6946) of having oligohydramnios within 7
      days, and those with low-normal amniotic fluid index values had a 16.3% chance
      (105/643) of having oligohydramnios with 7 days. Stratifying the results by
      gestational age reveals that patients at > or = 41 weeks of gestation had a 23.3%
      chance of having oligohydramnios within 4 days if the current amniotic fluid
      index was found to be 5 to 8 cm and a 7.4% chance if the current amniotic fluid
      index was found to be normal. Term (estimated gestational age of 37 to 40 weeks)
      patients had a similar risk of oligohydramnios in 4 days if the amniotic fluid
      index was low-normal (17.8%) but a risk of 3.6% if the amniotic fluid index was
      normal. CONCLUSIONS: For patients at < 41 weeks of gestation undergoing
      antepartum testing, weekly assessments of amniotic fluid index is probably
      adequate if the initial measurement is in the normal range (> or = 8 cm) because
      the risk of having oligohydramnios within 7 days is low (2.2%). For patients at <
      41 weeks of gestation whose initial amniotic fluid index measurement is in the
      low-normal range (5 to 8 cm), a scheme of twice-weekly assessment is justified on
      the basis of a higher risk for an amniotic fluid index < or = 5 cm within 4 days
      (12.3%). For all patients at > or = 41 weeks of gestation, twice-weekly amniotic
      fluid index assessments are recommended regardless of the initial measurement.

PMID- 8572031
TI  - Identification of human parvovirus B19 infection in idiopathic nonimmune hydrops
      fetalis.
AB  - OBJECTIVE: This retrospective study was designed to determine the incidence of
      B19 associated with idiopathic nonimmune hydrops fetalis by use of a sensitive
      molecular tool, the polymerase chain reaction assay. STUDY DESIGN: Placental and
      fetal tissues from 57 cases of nonimmune hydrops fetalis were analyzed for B19
      deoxyribonucleic acid. Thirty-four of these cases were classified as idiopathic.
      The remaining 23 cases had known, noninfectious-based causes. RESULTS: Eighteen
      percent of all cases (6/34) of idiopathic nonimmune hydrops fetalis contained B19
      deoxyribonucleic acid. In contrast, none of the 23 cases of known, noninfectious
      based nonimmune hydrops fetalis examined contained any B19 deoxyribonucleic acid.
      Presence of the virus was confirmed in each of the six cases by either B19
      specific deoxyribonucleic acid in situ hybridization or immunocytochemistry.
      However, histologic examination was unsuccessful at detecting characteristic
      viral-like inclusions in one third of the cases. CONCLUSION: Eighteen percent of
      cases of idiopathic nonimmune hydrops fetalis contained B19 deoxyribonucleic
      acid. This significant finding demonstrates the usefulness of polymerase chain
      reaction to aid in the differential diagnosis of this disease.

PMID- 8572032
TI  - Fetal heart rate and uterine contractility during maternal exercise at term.
AB  - OBJECTIVE: Our aim was to assess the physiologic response of human fetal heart
      rate and uterine contractility to moderately strenuous maternal exercise. STUDY
      DESIGN: We measured fetal heart rate and intrauterine pressure with the use of
      internal monitoring before, during, and after maternal exercise at a heart rate
      of 140 beats/min on a cycle ergometer in 30 term women admitted for elective
      induction of labor. The fetal heart rate tracings were assessed by three
      observers and were classified according to Fischer et al. and Nijhuis et al., and
      the frequency and intensity of uterine contractions were determined. RESULTS:
      Fetal outcome was good in all cases. There were no significant differences in
      Fischer scores between rest, exercise, and recovery periods. The fetuses
      displayed a heart rate pattern A and B, indicative of behavioral states 1F or 2F,
      85% of the time, with state changes apparently independent of exercise. Uterine
      activity increased significantly during the exercise period, with a 5.5-fold
      increase in contraction frequency and a fourfold increase in time-pressure
      integral compared with rest, with rapid recovery after the exercise. CONCLUSION:
      Exercise in healthy pregnant women at term does not cause a change in fetal heart
      rate pattern suggestive of fetal distress or a change in fetal behavioral
      pattern, but it does significantly increase uterine activity.

PMID- 8572033
TI  - Uptake of human immunodeficiency virus envelope protein gp120 by human
      trophoblast in culture.
AB  - OBJECTIVE: Our purpose was to determine whether human trophoblast has a cell
      surface CD4 antigen that will bind to gp120, the envelope protein of human
      immunodeficiency virus. STUDY DESIGN: Uptake of iodine 125-labeled gp120 by
      trophoblast in culture was measured. Particular attention was paid to technical
      details that may have caused the contradictory results reported by previous
      investigators: the source of the recombinant gp120, the method of
      radioiodination, and the isolation procedure of trophoblast to ensure elimination
      of contaminating cells, particularly macrophages. RESULTS: Uptake of transferrin
      free iodine 125-labeled gp120 to trophoblast was unaffected by adding a 200 molar
      excess of gp120, by preincubating gp120 with soluble CD4 to block the CD4 binding
      sites on gp120 and by preincubation of trophoblast with a blocking antibody to
      CD4 (OKT4a). In contrast, uptake of gp120 by CD4-positive H9 human lymphocytes
      was reduced 79% by a 200 molar excess of gp120 and > 50% by a CD4-blocking
      antibody. CONCLUSIONS: Uptake of gp120 to trophoblast is by a high capacity, CD4
      independent mechanism that is probably nonspecific and may be related to the
      mechanism for binding other circulating glycoproteins in maternal blood.

PMID- 8572034
TI  - The hematologic and plasma iron responses to severe fetal hemorrhage in the ovine
      fetus.
AB  - OBJECTIVE: We previously reported that the ovine fetus does not significantly
      increase its red blood cell production rate after a 40% loss of blood in spite of
      a transient elevation in plasma erythropoietin concentration. In this study we
      hypothesized that, in response to a more severe loss of blood, the ovine fetus
      would undergo a sustained rise in plasma erythropoietin concentration and an
      augmentation in its red blood cell mass expansion rate. STUDY DESIGN: Twelve
      chronically catheterized fetal sheep (six control and six hemorrhaged) were
      studied beginning at 126 +/- 1 (SE) days' gestation. Fetal blood volume, plasma
      volume, red blood cell mass, reticulocyte count, plasma erythropoietin level, and
      plasma iron level were measured for 10 consecutive days. On days 1, 2, and 3 the
      hemorrhaged fetuses had an average of 102 +/- 4 ml per day of blood removed at a
      rate of 1 ml/min for a total of 305 +/- 10 ml of blood removed. Statistical
      analysis was by one- and three-factor analysis of variance. RESULTS: Control
      animals had a progressive increase in blood volume, plasma volume, and red blood
      cell mass throughout the 10-day protocol. Reticulocyte counts and plasma iron and
      erythropoietin levels did not change. In fetuses at 24 hours after the third
      hemorrhage blood volume averaged 9.3% below (p = 0.03) and plasma volume averaged
      16.4% above (p = 0.04) that in the control animals. Thereafter blood and plasma
      volumes expanded at rates similar to controls. Erythropoietin increased (p <
      0.001) but returned to prehemorrhage values by day 7. Posthemorrhage expansion of
      the red blood cell mass in the hemorrhaged animals was 1.9 times controls (6.8%
      +/- 0.9%/day vs 3.5% +/- 0.5%/day, p = 0.003). Fetal reticulocyte counts remained
      elevated throughout the posthemorrhage observation period (p < 0.001). The fetal
      plasma iron concentration decreased (p < 0.0001) and remained depressed. The
      recovery of red blood cell mass and the 10-day mean plasma iron concentration
      were highly correlated (p = 0.01, r = 0.91). CONCLUSION: The ovine fetus
      significantly increases its release of red blood cells in response to a severe
      hemorrhage. Further, the ability of the fetus to restore its red blood cell mass
      appears to be dependent on the plasma iron concentration.

PMID- 8572035
TI  - Lipid peroxidation in cord blood at birth.
AB  - OBJECTIVE: The purpose of this study was to determine oxygen free radical
      activity in the neonate at birth and relate it to umbilical cord blood acid-base
      status. STUDY DESIGN: A series of 110 singleton deliveries had determination of
      two lipoperoxides in umbilical cord blood: malondialdehyde and organic
      hydroperoxide. Umbilical pH, PO2, PCO2, bicarbonate, and base excess were also
      measured. RESULTS: There was a significant association between lipoperoxides and
      cord blood pH and base excess. A significant difference existed in the levels of
      umbilical artery lipoperoxides between nonacidemic and acidemic fetus, as defined
      by an umbilical arterial pH < 7.20. CONCLUSION: There is a positive association
      between lipoperoxide production and acid-base balance at delivery.

PMID- 8572036
TI  - Perinatal mortality in twins and singletons matched for gestational age at
      delivery at > or = 30 weeks.
AB  - OBJECTIVE: Our purpose was to compare perinatal mortality between twins and
      singletons matched for gestational age at delivery with the hypothesis that
      perinatal mortality would be similar. STUDY DESIGN: A retrospective cohort study
      compared perinatal mortality in twins (790 babies) matched for gestational age at
      delivery at > or = 30 weeks with the next singleton. Perinatal mortality was also
      compared by expected growth (small and average for gestational age) and by the
      cause of the preterm delivery (medical indication, spontaneous preterm delivery,
      or preterm premature rupture of membranes with preterm delivery. RESULTS:
      Uncorrected perinatal mortality was significantly greater in singletons (56/1000)
      than in twins (26/1000) (p = 0.004). After major congenital anomalies were
      excluded, perinatal mortality remained significantly higher in singletons
      (25/1000) than in twins (11/1000) (p = 0.04). In preterm deliveries perinatal
      mortality was significantly greater in singletons (72/1000) than in twins
      (19/1000) (p = 0.0002). Perinatal mortality was significantly greater in small-
      compared with average-for-gestational-age neonates, whether singletons or twins
      (p = 0.005), and singleton small-for-gestational-age neonates had a significantly
      greater perinatal mortality (105/1000) than did twin small-for-gestational-age
      neonates (36/1000) (p = 0.02). Perinatal mortality was not significantly
      different between preterm singletons and twins delivered by spontaneous preterm
      labor. However, perinatal mortality in preterm singletons delivered for a medical
      indication (156/1000) was significantly greater than for twins (20/1000) (p =
      0.0006). CONCLUSIONS: At > or = 30 weeks at delivery, twins either had a
      perinatal mortality similar to, or less than singletons matched for gestational
      age at delivery. This suggests that when preterm delivery is controlled for
      perinatal mortality is not greater in twins. In twins, without risk factors for
      perinatal death, routine antepartum testing may not be indicated.

PMID- 8572037
TI  - Weight gain associated with prenatal smoking cessation in white, non-Hispanic
      women.
AB  - OBJECTIVE: Our purpose was to assess the effect of prenatal smoking cessation on
      maternal weight gain and infant birth weight in women who smoked at least five
      cigarettes per week. STUDY DESIGN: This prospective study followed up a sample of
      white, non-Hispanic pregnant smokers enrolled in three multispecialty clinics. By
      use of t tests, women quitting smoking before 28 weeks and continuing smokers
      were compared on total weight gain, Institute of Medicine weight gain categories,
      and infant birth weight. RESULTS: Quitters gained 36.6 pounds (SD 14.5) and
      smokers 28.9 pounds (SD 11.7) (p < 0.001). The relative risk of quitters gaining
      less than the Institute of Medicine minimum was 0.47 (95% confidence interval
      0.27 to 0.81). Quitters also gained more than Institute of Medicine standards
      (relative risk 1.74, 95% confidence interval 1.21 to 2.51), and they were 3.1
      times as likely to be delivered of infants weighing > 4000 gm (95% confidence
      interval 1.18 to 7.97). The four low-birth-weight babies were born to smokers
      with low weight pain. CONCLUSION: In this population smoking cessation is
      associated with a lower risk of gaining too little by Institute of Medicine
      standards and also with higher risk of gaining more than the Institute of
      Medicine standard and having infants weighing > 4000 gm. The clinical
      significance of these effects needs to be determined in further studies.

PMID- 8572038
TI  - Intraamniotic deamino(D-Arg8)-vasopressin: prolonged effects on ovine fetal urine
      flow and swallowing.
AB  - OBJECTIVE: Fetal urine is the main source of amniotic fluid, and alterations in
      urine production have an impact on amniotic fluid dynamics. Intraamniotic
      arginine vasopressin is absorbed into fetal plasma, but fetal antidiuretic
      responses may be obscured by vasoconstrictor (V1 receptor) actions of arginine
      vasopressin. We determined the effects of intraamniotic administration of a
      specific V2 receptor agonist, deamino(D-Arg8)-vasopressin, on fetal plasma
      arginine vasopressin immunoreactivity, fetal urine output, and swallowing. STUDY
      DESIGN: Six chronically prepared pregnant ewes (129 +/- 1 days' gestation)
      received a single deamino(D-Arg8) (50 micrograms injection into the amniotic
      fluid with subsequent measurement of fetal plasma arginine vasopressin
      immunoreactivity, fetal urine flow and osmolality, and fetal swallowing. RESULTS:
      Within 30 minutes of deamino(D-Arg8)-vasopressin administration, fetal plasma
      arginine vasopressin immunoreactivity (4.5 +/- 0.5 to 76.4 +/- 21.9 pg/ml) and
      urine osmolality (135 +/- 13 to 285 +/- 43 mOsm/kg H2O) significantly increased
      and urine flow decreased (0.18 +/- 0.01 to 0.05 +/- 0.01 ml/kg per minute). After
      48 hours urine flow remained reduced (0.08 +/- 0.03 mg/kg per minute) and
      osmolality remained elevated (399 +/- 18 mOsm/kg H2O). There were no changes in
      fetal swallowing, systolic (64 +/- 3 mm Hg) or diastolic (42 +/- 3 mm Hg) blood
      pressure, or heart rate (169 +/- 6 beats/min). CONCLUSIONS: Intraamniotic
      deamino(D-Arg8)-vasopressin administration evokes persistent fetal antidiuresis
      in the absence of arginine vasopressin-induced fetal cardiovascular effects or
      changes in fetal swallowed volume, indicating its suitability as a potential
      therapeutic agent in amniotic fluid volume disorders such as polyhydramnios.

PMID- 8572039
TI  - A one-year multicenter study of efficacy and safety of a continuous, low-dose,
      estradiol-releasing vaginal ring (Estring) in postmenopausal women with symptoms
      and signs of urogenital aging.
AB  - OBJECTIVE: We studied the efficacy, safety, and acceptability of an estradiol
      releasing (6.5 to 9.5 micrograms per 24 hours) silicone vaginal ring (Estring) in
      postmenopausal women with symptoms and signs of urogenital aging during a
      treatment period of 1 year. STUDY DESIGN: The study was open with blind analysis
      of vaginal cytologic testing. In addition to gynecologic examination, subjective
      symptoms were assessed and vaginal pH and urinary samples (for bacteriuria) were
      obtained before insertion of Estring. This procedure was repeated every 3 months
      up to 1 year's treatment, together with requests concerning acceptability and
      adverse experiences. At inclusion and end of Estring treatment, vaginal smears
      for evaluation of cytologic results were obtained. RESULTS: Estring induced a
      high maturation value in the vaginal mucosa and restored vaginal pH to levels
      normality seen in fertile women (< 5.5). For most variables a 90% responder rate
      (proportion of cured and improved patients) was found after 3 months and up to 1
      year regarding subjective symptoms and objective signs of vaginal mucosal
      atrophy. Twenty-eight (20%) of 136 women, withdrew from the study, 8 (6%) of them
      because of adverse events. Three women reported vaginal bleeding, none associated
      with malignancy or endometrial proliferation. Ten (7%) reported vaginal
      irritation, and in two cases vaginal ulcers were found. About 90% did not remove
      the ring during any of the 3-month treatment periods, and 78% used the four
      consecutive rings continuously up to 1 year. The ring was given a strong
      preference (p < 0.001) by patients with previous experience of other
      administration forms. CONCLUSION: Estring represents a safe, highly effective,
      and very well-accepted administration form for long-term treatment of urogenital
      disorders caused by estrogen deficiency in postmenopausal women.

PMID- 8572041
TI  - Including occupational therapy in low vision rehabilitation.

PMID- 8572040
TI  - Effects of hormone replacement therapy on the mammary gland of surgically
      postmenopausal cynomolgus macaques.
AB  - OBJECTIVE: Our purpose was to define the proliferative response and receptor
      status in the mammary glands of surgically postmenopausal macaques given hormone
      replacement therapy, equivalent for monkeys to that given women. STUDY DESIGN:
      Surgically postmenopausal adult female cynomolgus macaques (Macaca fascicularis)
      were given either no treatment (n = 26), conjugated equine estrogens (n = 22), or
      combined therapy with conjugated equine estrogens and medroxyprogesterone acetate
      (n = 21). Drugs were administered in the diet, at doses equivalent on a caloric
      basis to 0.625 mg per woman per day for conjugated equine estrogens and 2.5 mg
      per woman per day for medroxyprogesterone acetate, for 30 months. Mammary gland
      proliferation was assessed subjectively and by morphometric and stereologic
      means. Estrogen receptor and progesterone receptor content and proliferation were
      studied by immunohistochemistry. RESULTS: In this model combined therapy with
      conjugated equine estrogens and medroxyprogesterone acetate induced greater
      proliferation than did conjugated equine estrogens alone. The percentage of
      estrogen receptor-positive cells was decreased in the conjugated equine estrogens
      plus medroxyprogesterone acetate group. The percentage of progesterone receptor
      positive cells was increased by treatment with conjugated equine estrogens alone.
      CONCLUSION: These results indicate a proliferative response of mammary gland
      epithelium to therapy with conjugated equine estrogens plus medroxyprogesterone
      acetate in postmenopausal macaques. The clinical implication of this finding may
      be a greater risk for development of breast neoplasms in women receiving combined
      hormone replacement therapy.

PMID- 8572042
TI  - Special issue on low vision.

PMID- 8572043
TI  - Living with low vision: a personal and professional perspective.
AB  - Unlike most readers of this special issue, I have been both a consumer and
      provider of rehabilitation services. A retinal hemorrhage that occurred when I
      was in my late twenties signaled the beginning of delayed-onset retinopathy of
      prematurity--a condition that has been further complicated since that time. In
      this article, I offer a glimpse of what living with low vision is like by
      describing activities in my own life and accommodations I have made. My hope is
      that therapists will learn more about the realities of living with low vision and
      will seek our additional information that they will incorporate into their
      practice.

PMID- 8572044
TI  - Basic concepts and terms for low vision rehabilitation.
AB  - As the involvement of occupational therapists in the rehabilitation of people
      with visual impairments increases, it is important for all professionals involved
      to communicate clearly by using the most accurate terminology. This article
      suggests the most appropriate use of terms and concepts. It recommends that the
      distinctions between the various aspects of vision loss be recognized and that
      the old dichotomy of legally blind versus legally sighted be replaced by the more
      detailed classification of the International Classification of Diseases, 9th
      revision, Clinical Modification (ICD-9-CM), which recognizes multiple levels of
      visual performance.

PMID- 8572046
TI  - Providing low vision rehabilitation services with occupational therapy and
      ophthalmology: a program description.
AB  - This article describes a low vision rehabilitation program operating within a
      hospital-based outpatient rehabilitation clinic. The program uses a team approach
      combining ophthalmology and occupational therapy services. Patients are referred
      to the program by their primary care physician for a low vision evaluation
      completed jointly by the ophthalmologist and occupational therapist. The
      ophthalmology portion of the evaluation includes assessment of visual acuity,
      contrast sensitivity function, and macular perimetry with a scanning laser
      ophthalmoscope. The occupational therapy evaluation focuses on assessing the
      functional limitations experienced by the patient due to the vision loss and
      determining how the patient is best able to use remaining vision to complete
      daily activities. Occupational therapy treatment emphasizes training the patient
      to use remaining vision as efficiently and effectively as possible to complete
      daily activities and includes training in use of optical devices. Because of the
      specialized nature of the service provided, additional postgraduate preparation
      is needed to enable occupational therapists to provide effective low vision
      rehabilitation.

PMID- 8572045
TI  - Adaptation to macular scotomas in persons with low vision.
AB  - Persons with scotomas in their central 20 degrees of vision often do not notice
      these blind spots within their visual field and have visual performance
      difficulties far exceeding what would be expected from standard vision tests.
      Before persons with macular scotomas can be assisted to optimally use their
      remaining vision for a better quality of life, more must be known about how the
      visual system adapts to a macular scotoma. Important issues include spatial and
      temporal characteristics of perceptual completion and metamorphopsia, development
      of preferred retinal loci for fixation and visual search, and dynamics of the
      preferred retinal locus development in terms of the changes in the eye movement
      system. With a full understanding of the visual system's adaptation to macular
      scotomas, new low vision devices and training techniques can be proposed to
      promote independence in activities of daily living for the person with low
      vision.

PMID- 8572047
TI  - Functional considerations in evaluation and treatment of the client with low
      vision.
AB  - In evaluating and treating clients who have low vision, the occupational
      therapist must consider factors in addition to typical measures of the client's
      visual acuity, field loss, and oculomotor control. It is important to consider
      the functional implications of the client's ocular pathology, including
      illumination needs, contrast sensitivity, sensitivity to glare, and need for
      magnification as well as environmental factors such as the amount of pattern in a
      visual task, the amount of lighting and contrast available, and the conditions
      under which the task is performed. These factors are all relevant to occupational
      therapy low vision rehabilitation because each may influence the way in which a
      client uses his or her residual vision and achieves successful adaptation. This
      article provides an overview of these factors and presents a suggested protocol
      for evaluation of the client with low vision.

PMID- 8572048
TI  - Considerations in evaluation and treatment of the child with low vision.
AB  - Habilitation of infants and children with visual impairments should be based on a
      thorough understanding of their visual capabilities and limitations.
      Comprehensive evaluation of visual function includes measurement of visual
      acuity, contrast sensitivity, visual field, color vision, adaptation, visual
      sphere, accommodation, and oculomotor functions. It is best completed through a
      team approach that uses therapists, special educators, and physicians. A complete
      evaluation also includes examination of the effect of other motor functions on
      the use of vision. Nearly all aspects of a child's vision can be measured in play
      situations with tests that are easy to use. However, further education of
      nonphysician team members in refractive errors, optics, and function of optical
      devices may be necessary to ensure an accurate and thorough evaluation.

PMID- 8572049
TI  - Understanding cortical visual impairment in children.
AB  - This article presents a review of the literature and a case study on a child with
      cortical visual impairment. The literature review covers the diagnosis, etiology,
      prevalence, prognosis, and a comparison of the differences between children with
      cortical visual impairment and those with ocular impairment. The case study
      presents occupational therapy intervention strategies specific to cortical visual
      impairment and results of treatment.

PMID- 8572050
TI  - Occupational therapy and the person with diabetes and vision impairment.
AB  - Diabetes affects 5.2% of the population; many of those persons experience loss of
      vision as one complication of the disease. Occupational therapists are treating
      these persons, often for other resulting complications (such as stroke or
      amputations), or are being asked to adapt techniques or equipment (such as
      insulin-drawing devices) needed for diabetes management. Because no guidelines
      exist for occupational therapy with persons with diabetes or vision loss or both,
      occupational therapists may be unsure of appropriate treatment approaches. Among
      the approaches described in the occupational therapy literature, common ones
      include collaboration with other professionals and incorporation of one or more
      aspects of the diabetes regimen into the person's life-style. When addressing
      persons who have both diabetes and vision loss, therapists consider their own
      knowledge base as well as the persons' needs in managing their diabetes.
      Treatment ideas include enhancing the visual environment or incorporating tactile
      and auditory feedback with self-management tasks such as testing blood glucose
      levels. Collaboration with and referral to diabetes and low-vision professionals
      are adjuncts to therapy and ensure a comprehensive and ongoing diabetes
      management program.

PMID- 8572051
TI  - Overview of technology for low vision.
AB  - This article provides an overview of technology resources and services to assist
      persons with low vision in maintaining independent function in the home,
      community, and educational and vocational settings. Case studies are provided to
      demonstrate the integration of technology into the lives of persons with low
      vision.

PMID- 8572052
TI  - Low vision rehabilitation for a patient with a traumatic brain injury.
AB  - The client described in this article had undergone intensive rehabilitation for
      physical and cognitive deficits that resulted from an anoxic encephalopathy. Her
      recovery was good in all areas except visual functioning. Her reading and writing
      deficits were initially thought to result from visual-perceptual problems. A low
      vision evaluation identified the deficits as resulting from a macular visual
      field loss. Warren (1993) has proposed that an intact visual field is one of the
      basic components of vision that must be present before higher visual processing
      can occur. Until the macular perimetry was performed on this client, the extent
      of her central field loss was unknown, and the treatment that focused on the
      higher level visual processing was unsuccessful. The low vision program targeted
      the central field loss as the probable cause for her difficulties and an
      effective treatment protocol was established. The client was instructed regarding
      the nature of her visual field deficit and was trained in methods to compensate
      for this deficit. Although she has not returned to work as of this writing
      because of financial disincentives, the training resulted in a measurable and
      functional improvement in the client's ability to read continuous print text, a
      task she had not performed in 4 years, and in her ability to perform all writing
      tasks needed for daily living.

PMID- 8572053
TI  - Do occupational therapists have a primary role in low vision rehabilitation?

PMID- 8572054
TI  - Rescinding policy on using ICIDH terms was ill-considered.

PMID- 8572055
TI  - Yerxa's criticisms of cross training are appropriate.

PMID- 8572056
TI  - Cochlear implants: it's time to rethink.

PMID- 8572057
TI  - Effect of profound hearing loss on a central auditory nucleus.
AB  - The present study was designed to investigate the type and extent of degeneration
      occurring in the human central auditory system subsequent to profound hearing
      loss. The authors have examined the size of one population of neurons in the
      ventral cochlear nucleus in seven subjects with profound hearing loss
      (audiometric responses poorer than 90-100 dB HL). Six normal subjects, ages 35
      78, were used as controls. Cell size in the hearing-impaired subjects ranged from
      normal to reduced by more than 50 percent. Two factors appear to contribute to
      the variability in cell size reduction. The correlation coefficient (Spearman rs)
      of cell size with duration of profound deafness was -0.48, indicating a moderate
      tendency for neurons to become smaller with longer periods of deafness. The
      correlation coefficient of cell size with number of surviving cochlear ganglion
      cells was 0.73, indicating a stronger tendency for neurons to be larger with
      greater eighth nerve innervation of the cochlear nucleus. Two cases of Scheibe
      degeneration showed the most severe degenerative change in the central auditory
      system.

PMID- 8572058
TI  - Distortion product otoacoustic emissions in the elderly.
AB  - Clinical interest in otoacoustic emissions (OAEs) is increasing. These can be
      elicited rapidly in a number of test paradigms that reflect the functional status
      of the outer hair cells of the organ of Corti. Distortion product otoacoustic
      emissions (DPOEs) have been well described in infants, and adults, but not in the
      elderly. The value of DPOE testing as a means of objective assessment of cochlear
      function is still being studied. The authors obtained DPOEs in 129 ears of 71
      elderly volunteer subjects (age 56-93 yr) and in 16 ears of eight young adults
      (age 19-26 yr) with normal pure-tone thresholds (PTTs). The relation between
      DPOEs and PTTs, as expressed by the r2 statistic, was 0.18, 0.46, and 0.30 at 1,
      2, and 4 kHz, respectively. Amplitudes of DPOEs did not decrease significantly
      with age, when adjusted for PTTs. Sensitivity and specificity, receiver operating
      characteristic curves, as well as posterior probabilities were analyzed to
      elucidate the relation between DPOEs and PTTs. At 2 kHz 90 percent of ears with
      PTTs 40 dB HL or less exhibited DPOEs of -4 dB SPL or greater, and all ears with
      PTTs greater than 40 dB HL had either no measurable DPOEs or DPOE amplitude less
      than 4 dB SPL.

PMID- 8572059
TI  - Cochlear implant-related osteoneogenesis in an animal model: fluorescent
      labeling.
AB  - Cochlear osteoneogenesis may result from a variety of pathologic conditions,
      including cochlear implantation. The etiology of cochlear osteoneogenesis
      following implantation, however, is not known. Cochlear implant-related
      osteoneogenesis has been demonstrated in laboratory animals, but the specific
      cause, extent, or time-course of this process has not been determined. In this
      preliminary study, fluorescent bone labels were used to assess osteoneogenesis in
      six chinchillas in three experimental categories: surgical trauma to the cochlea,
      chronic nonstimulated cochlear implantation, and intrascalar neomycin infusion.
      Computer image analysis was used to measure the area of labeled bone on
      representative mid-modiolar histologic sections. The amount of bone deposition
      was greatest in ears treated with intracochlear neomycin (mean = 2.3835 mm2, SD =
      3.7308). Surgical trauma alone (mean = 0.9549 mm2, SD = 1.384) and chronic
      implantation without stimulation did not produce substantial bone growth when
      compared to contralateral control ears (mean = 0.0574 mm2, SD = 0.0731).
      Fluorochrome labeling was also used to differentiate types of bone deposition.
      The morphology and timing of new bone growth appeared to be related to the type
      of cochlear injury. These results confirm that intracochlear neomycin may
      contribute to osteoneogenesis in animal studies of cochlear implantation. This
      study supports the use of fluorescent bone labeling in the evaluation of cochlear
      osteoneogenesis.

PMID- 8572060
TI  - Indications for cranial nerve monitoring during otologic and neurotologic
      surgery.

PMID- 8572061
TI  - Technical modifications to the middle fossa craniotomy approach in removal of
      acoustic neuromas.
AB  - With the increased use of gadolinium-enhanced magnetic resonance imaging studies
      to detect acoustic neuromas, smaller tumors are discovered more frequently. The
      middle fossa craniotomy approach for removal of small tumors is ideal for hearing
      preservation. The authors report hearing preserved at or near the preoperative
      levels in 71 percent of a series of 24 consecutive patients in whom the middle
      fossa craniotomy approach was employed. Several technical modifications,
      including more extensive bony exposure medially, tumor dissection in a medial-to
      lateral direction, and topical application of papaverine to the cochlear nerve at
      the modiolus, have enhanced the ability to preserve hearing.

PMID- 8572063
TI  - Central dizziness associated with cerebral blood flow disorders.
AB  - This retrospective study describes the use of transcranial Doppler (TCD) and
      history for further defining and diagnosing cerebral blood flow (CBF) disorders
      in patients with central dizziness. Central dizziness was defined as dizziness of
      nonlabyrinthine, non-peripheral causes. It was believed that at least some of the
      causes for central dizziness are not unknown but are associated with CBF
      disorders. Fifty patients who presented with central dizziness were examined and
      subsequently tested with TCD. In 33 of 50 cases (66%) a diagnosis could be
      assigned after TCD; whereas, on the basis of both history and TCD a diagnosis was
      assigned to 38 patients (76%).

PMID- 8572062
TI  - Facial nerve function following middle fossa and translabyrinthine acoustic tumor
      surgery: a comparison.
AB  - Postoperative facial function was compared for middle cranial fossa and
      translabyrinthine removal of acoustic tumors. Included were 164 primary acoustic
      tumor surgeries performed between 1988 and 1991 in patients with normal
      preoperative facial function; postoperative House-Brackmann facial function grade
      available immediately postoperatively, at time of discharge and at 1 year or more
      postoperatively; and a tumor 1.5 cm or smaller. There were 116 translabyrinthine
      surgeries and 48 middle fossa surgeries. There was no significant difference in
      facial function results between the two surgical approaches at any of the three
      postoperative time intervals. Immediate postoperative facial function grade I or
      II was present in 90 percent of patients who underwent the middle cranial fossa
      approach, and in 90 percent of those with translabyrinthine surgery. By long-term
      follow-up, grade I or II function was recorded after 96 percent of middle fossa,
      and 91 percent of translabyrinthine surgeries. Results were similar when
      evaluating subgroups of those with tumors measuring 1.0 or smaller and 1.1-1.5
      cm. There was also no difference in facial function result between superior and
      inferior vestibular nerve tumors with either approach. The authors conclude that,
      in an experienced center, long-term postoperative facial function outcome is not
      a basis for selecting surgical approach for tumors measuring 1.5 cm or less.

PMID- 8572064
TI  - Surgical decompression of Chiari I malformation for isolated progressive
      sensorineural hearing loss.
AB  - Progressive sensorineural hearing loss has been associated with Chiari type I
      malformation. Retrocochlear features on auditory brainstem response testing have
      been reported; however, debate exists over the exact location of the defect.
      Surgical decompression may be beneficial if brainstem or vascular compression
      have played a significant role in the pathophysiology of the hearing loss. Lack
      of specific audiologic data before and after surgical decompression has kept
      surgical decision making theoretic. This report presents the case of a 10-year
      old boy with a progressive, asymmetric sensorineural hearing loss without other
      neurologic abnormalities. He underwent a posterior fossa decompression that
      resulted in stable hearing over the 2 years he was followed postoperatively.
      Preoperative and postoperative audiologic and evoked response features are
      described, and the rationale for operating with symptoms limited to hearing loss
      is discussed.

PMID- 8572065
TI  - Detection of viral DNA in endolymphatic sac tissue from Meniere's disease
      patients.
AB  - Neurotropic viruses have been postulated to play a role in the development of
      Meniere's disease (MD). The purpose of this study was to evaluate the
      endolymphatic sacs of patients undergoing surgery for MD in a single-blind study
      for evidence of herpes simplex virus (HSV), varicella zoster (VZ), or
      cytomegalovirus (CMV) DNA. Polymerase chain reaction (PCR) was used as the method
      of detection because of its sensitivity, specificity, and applicability to fresh,
      as well as fixed tissues. Twenty-two patients with MD and 11 control patients
      with vestibular schwannomas had a portion of the endolymphatic sac removed at the
      time of surgery. The specimens were then evaluated for herpes simplex type and 2,
      varicella zoster, and cytomegalovirus DNA. Herpes simplex virus DNA was detected
      in 2 of the 22 extracts from the endolymphatic sacs obtained from patients with
      MD. There was no evidence of a positive signal obtained with any of the other
      viral DNA probes when PCR was performed on the control tissue extracts or the
      other MD tissue extracts. These results do not demonstrate a significant
      difference and do not statistically support the postulate that ongoing viral
      infection in the endolymphatic sac is a frequent factor in the development of
      Meniere's disease.

PMID- 8572066
TI  - Determination of the position of nucleus cochlear implant electrodes in the inner
      ear.
AB  - Accurate determination of intracochlear electrode position in patients with
      cochlear implants could provide a basis for detecting migration of the implant
      and could aid in the selection of stimulation parameters for sound processor
      programming. New computer algorithms for submillimeter resolution and 3-D
      reconstruction from spiral computed tomographic (CT) scans now make it possible
      to accurately determine the position of implanted electrodes within the cochlear
      canal. The accuracy of these algorithms was tested using an electrode array
      placed in a phantom model. Measurements of electrode length and interelectrode
      distance from spiral CT scan reconstructions were in close agreement with those
      from stereo microscopy. Although apparent electrode width was increased on CT
      scans due to partial volume averaging, a correction factor was developed for
      measurements from conventional radiographs and an expanded CT absorption value
      scale added to detect the presence of platinum electrodes and wires. The length
      of the cochlear canal was calculated from preoperative spiral CT scans for one
      patient, and the length of insertion of the electrode array was calculated from
      her postoperative spiral CT scans. The cross-sectional position of electrodes in
      relation to the outer bony wall and modiolus was measured and plotted as a
      function of distance with the electrode width correction applied.

PMID- 8572067
TI  - Nonorganic hearing loss in cochlear implant candidates.
AB  - Five patients undergoing assessment for cochlear implantation have been found to
      have a nonorganic hearing loss (pseudohypacusis). This phenomenon has not been
      reported previously in this patient population. The cases are presented and the
      causes, detection, and management of this condition are discussed.

PMID- 8572068
TI  - Pathogenesis of attic retraction pocket and cholesteatoma as studied by computed
      tomography.
AB  - It is hypothesized that blockade of the tympanic isthmus causes isolation of the
      attic and the adjacent middle ear spaces and that subsequent building up of the
      negative pressure in these spaces results in retraction of the pars flaccida,
      leading to formation of attic retraction pockets and cholesteatomas. To examine
      this theory, computerized tomographic (CT) findings of these conditions were
      evaluated in a series of 53 ears with retractions of the pars flaccida (attic
      retractions of Tos type II or deeper), including both retraction pockets and
      cholesteatomas. In 26 of 28 ears with attic retraction pockets, at least a
      portion of attic was aerated, and in 22 of these 26 ears, the mastoid antrum was
      also aerated. In contrast, in the 25 cases with attic cholesteatomas, these
      numbers decreased to 10 and 5, respectively, and the lack of aeration of the
      attic was demonstrated in 15 of 25 (60%) of the cases. In three cases of
      cholesteatoma, follow-up CT revealed either growth of a cholesteatoma from a
      retraction pocket or development of a small cholesteatoma into a large one. In
      these ears it was seen that the well-pneumatized attic and mastoid antrum seen in
      the initial CT was depleted by the growth of cholesteatoma that took place over a
      period of 4 months to 2 years. These results, showing good patency of the aditus
      and a pneumatized antrum in early stages of most cases of retraction pockets and
      cholesteatomas, are not in agreement with the hypothesis that the blockade of the
      tympanic isthmus is responsible for the pathogenesis of retraction pockets and
      cholesteatomas originating in the pars flaccida.

PMID- 8572069
TI  - Tympanic membrane changes in experimental otitis media with effusion.
AB  - A tympanometric in vitro model was used to measure the mechanoacoustic properties
      of the tympanic membrane. Impedance measurements were made during the early
      course (1-21 days) of experimentally induced otitis media with serous effusion in
      the Mongolian gerbil. A more severe form of otitis media with mucoid effusion was
      produced by electrocauterization of the nasopharyngeal orifice of the eustachian
      tube. The dynamic peak values of the acoustic susceptance were significantly
      reduced early in the course of serious otitis media, indicating increased
      stiffness of the tympanic membrane. In mucoid otitis media, the same reaction of
      the tympanic membrane was predominant, but the reverse reaction also was recorded
      in a few ears. These results indicate that alterations of the mechanoacoustic
      stiffness of the tympanic membrane occur during otitis media with effusion. Such
      changes may play an important role in the further course of the disease. The
      clinical implications of the tympanic membrane stiffness changes are discussed.
      Significant histopathologic changes were encountered in all cell layers, whereas
      the collagen fiber layer of the pars tensa appeared intact until 4 weeks of
      disease.

PMID- 8572070
TI  - Ofloxacin eardrop treatment for active chronic suppurative otitis media:
      prospective randomized study.
AB  - This report presents a prospective randomized study of 0.3 percent ofloxacin
      eardrops for the treatment of active chronic suppurative otitis media. Twenty
      nine patients were treated with ofloxacin eardrops for 1 week, and another 27
      patients were treated with Augmentin for 1 week. One week after completion of
      treatment, 22 (76%) patients of the group treated with ofloxacin had dry ears,
      and only seven (26%) patients treated with Augmentin had dry ears. Ofloxacin
      eardrops were effective in the initial treatment of active chronic suppurative
      otitis media.

PMID- 8572071
TI  - Long-term hearing results following stapedotomy.
AB  - Stapedotomy, or small fenestra stapes surgery, offers several advantages over
      total stapedectomy, including less postoperative vertigo and better closure of
      the air-bone gap at higher frequencies. Although early postoperative results are
      encouraging for the small fenestra technique, few data are available for longer
      follow-up periods. In this retrospective study, the hearing results of 35
      stapedotomy patients, representing 37 operated ears, were analyzed. Each patient
      had a follow-up period ranging from 5 to 11 years, with audiograms obtained
      preoperatively, postoperatively, and at the longterm follow-up intervals. Data
      obtained included air conduction, bone conduction, and speech discrimination for
      both ears. The long-term hearing results of the small fenestra technique compared
      favorably to those reported for total stapedectomy, although a statistical
      analysis is difficult because of the differing methods used to report the data.
      Results showed a linear deterioration of air conduction thresholds over time,
      which corresponded to a decrease of bone conduction thresholds in the operated
      ear. The rate of deterioration of bone conduction appeared to be the same as that
      associated with presbycusis alone. After good initial closure of the air-bone gap
      at all measured frequencies, there was no significant increase in conductive
      hearing loss with time. In the nonoperated ear, the bone conduction for the
      speech frequencies deteriorated at a rate significantly higher than that for the
      operated ear and was probably related to Carhart's effect.

PMID- 8572072
TI  - Impaired word recognition in noise by patients with noise-induced cochlear
      hearing loss: contribution of temporal resolution defect.
AB  - Fifteen patients with mild noise-induced cochlear hearing loss reported a
      selective difficulty in understanding speech in noisy settings. To examine the
      hypothesis that a temporal resolution defect was responsible for this difficulty,
      the patients were tested for their recognition of monosyllabic words presented
      against continuous and interrupted wide-band noise backgrounds, at each of seven
      signal-to-noise ratios. Their recognition performance was compared with that of
      normal listeners studied with the same paradigms. By comparison with the
      controls, the group with cochlear hearing loss showed a significant recognition
      impairment only for words presented against the interrupted masker. This finding
      was in keeping with the existence of a temporal resolution defect in cochlear
      disease, though it need not indicate a stimulus timing defect at the level of
      individual cochlear neurons.

PMID- 8572073
TI  - Autologous fibrin glue for tympanoplasty.
AB  - To produce autologous fibrin glue (AFG) of improved quality, the concentration
      and amount of materials for AFG were modified. The quality of AFG was assessed
      through determination of fibrinogen level in plasma, observation of product
      during production, and testing for bonding strength before application. The AFG
      produced under these conditions was used successfully as a helpful adjunct in
      middle ear surgery.

PMID- 8572074
TI  - Doc's discussion at HEC.

PMID- 8572075
TI  - Management of the internal carotid artery (ICA) when it must be occluded during
      skull base tumor or aneurysm surgery.

PMID- 8572076
TI  - Perilymphatic fistula with no visible leak of fluid into the middle ear: a new
      method of intraoperative diagnosis using electrocochleography.

PMID- 8572077
TI  - Anecdotal evidence.

PMID- 8572078
TI  - Otology and neurotology in America: state of the specialty.

PMID- 8572079
TI  - Computer-stimulated test fitting of an implantable hearing aid using implantable
      hearing aid using three-dimensional CT scans of the temporal bone: preliminary
      study.
AB  - In preparation for future implantation of the implantable middle ear transducer
      in patients, a method was sought for preoperatively test fitting a model of the
      device, using computer generated three-dimensional (3-D) temporal bone images
      derived from spiral computed tomography (CT) data. A 3-D model of the implantable
      middle ear transducer was designed using NIH Image software on a Macintosh
      computer. High resolution human temporal bone CT scans were obtained using a
      spiral CT scanner (Siemens Somatom Plus S). The 3-D transducer model was
      superimposed onto 3-D reconstructions of the temporal bone using ANALYZE software
      on a computer graphics workstation (Sun SPARCstation 10), showing the transducer
      "implanted" in the temporal bone. Measurements were validated using a cadaver
      temporal bone. This process produced images demonstrating the "fit" of the
      current transducer design in the mastoid region of the adult temporal bone. It
      permitted assessment of the proximity of surrounding structures such as the
      external auditory meatus, dura, or sigmoid sinus. Preliminary cadaver validation
      measurements confirmed the accuracy of this method. Three-dimensional CT is a
      feasible method for preoperative planning of the surgical implantation of devices
      in the temporal bone. This method of 3-D test fitting will be used in the future
      to determine optimum orientation and size limitations for human implantable
      devices.

PMID- 8572080
TI  - Role of autoimmunity in contralateral delayed endolymphatic hydrops.
AB  - Contralateral delayed endolymphatic hydrops is described as the development of
      fluctuating hearing loss and episodic vertigo in a normal ear years following
      sensorineural hearing loss in the opposite ear. This condition is a variant of
      delayed endolymphatic hydrops in which new symptoms of severe episodic vertigo
      develop years later in an ear that has lost most or all of its hearing. The
      possible etiologies of these two conditions are unknown and may be different.
      This report presents seven cases of the contralateral form of this disease and
      experimental evidence that suggests that these patients may be suffering from the
      initiation of an autoimmune event directed against the remaining inner ear. In
      Western blot analysis, their serum was reacted against cow cochlear inner ear
      antigen preparations, and six of the seven cases had serum antibodies directed
      against a 68 or a 35-36 kilodalton (kd) molecular weight antigen in contrast to
      three of 43 normal controls (p < .001 Fisher's exact test), the significance of
      which had previously been reported for autoimmune inner ear disease.

PMID- 8572081
TI  - Loss of perilymph affects electrocochleographic potentials in the guinea pig.
AB  - Alterations of electrocochleographic (ECoG) potentials recorded from guinea pig
      cochleae have been reported to occur following round window (RW) membrane
      perforation (perilymphatic fistula). To further evaluate the pathophysiology of
      perilymphatic fistula, a study was conducted of the short-term effects of acute
      RW membrane perforation on the amplitude of the summating potential (SP) and the
      action potential (AP), and the SP:AP ratio. Acute RW membrane perforation was
      produced in 15 Hartley guinea pigs. The animals were placed in a head dependent
      position, so that some perilymph would drain from the inner ear following RW
      perforation. For both click and low frequency tone burst stimuli (2 kHz), the
      mean AP amplitudes showed variable but progressive deterioration with time
      following RW membrane perforation. Action potential latencies showed a
      significant increase with time for both click and tone burst stimuli. Summating
      potential amplitudes for click and tone burst were typically stable or slightly
      decreased. Interanimal variability of all measures was typically high. However,
      AP and SP amplitudes in the same animal were consistently and differentially
      affected by perforation of the RW membrane. There also were differential effects
      on the positive and the negative components of the SP, suggesting the interplay
      of several generator mechanisms. The authors conclude that AP amplitude and,
      consequently, the SP:AP ratio are sensitive to the creation of a perilymphatic
      fistula. These results provide support for the use of ECoG tests in the diagnosis
      of perilymphatic fistula.

PMID- 8572082
TI  - Venous infarction following translabyrinthine access to the cerebellopontine
      angle.
AB  - Between July 1988 and August 1992, 141 tumors of the cerebellopontine angle were
      surgically removed through a variety of transtemporal approaches. Superior
      petrosal sinus resection was performed in 44 of these patients with either large
      tumors in the vertical dimension or contracted mastoid anatomy, in an effort to
      enhance intradural tumor exposure and facial nerve identification. Three patients
      who underwent superior petrosal sinus resection developed early postoperative
      temporoparietal venous infarction with transient expressive aphasia. The
      ipsilateral cavernous sinus was entered and packed during tumor dissection in all
      three cases, and one patient also had sacrifice of the petrosal vein. This report
      reviews intradural cortical venous anatomy as it relates to transtemporal access
      to the cerebellopontine angle. Three cases of postoperative venous infarction are
      presented to emphasize the importance of the venous collateral circulation to the
      cavernous sinus in patients having undergone superior petrosal sinus resection.

PMID- 8572083
TI  - Polyamine changes in the vestibular nuclei of guinea pigs following
      labyrinthectomy.
AB  - Vestibular compensation is a process of behavioral recovery from ocular, motor
      and postural disorders following unilateral damage to the vestibular end-organ.
      Although restoration of the normal resting discharge rate in the ipsilateral
      vestibular nuclei is important in compensation, the biochemical and molecular
      mechanisms mediating recovery are largely unknown. The ornithine decarboxylase
      polyamine pathway is activated in the nervous system following axotomy or
      denervation. The authors postulate that changes in polyamines mediate vestibular
      compensation. Within 150-micron brain stem coronal section micropunches analyzed
      by high performance liquid chromatography techniques, the polyamine spermidine
      was significantly increased in the ipsilateral lateral vestibular nucleus 8 hours
      following labyrinthectomy in the guinea pig model. Because naturally occurring
      polyamines modulate excitatory amino acid receptors (N-methyl-D-aspartate [NMDA])
      which in turn mediate neurotransmission between primary afferents and second
      order vestibular neurons, stimulation of polyamine pathways following neural
      injury may play a critical role in compensation.

PMID- 8572084
TI  - Comparison of endoscopic and surgical explorations for perilymphatic fistulas.
AB  - A history suggestive of perilymphatic fistula (PLF) often prompts repeated
      tympanostomies to establish a diagnosis and perform a repair. Two patients having
      multiple previous explorations for perilymphatic fistulas were reoperated,
      comparing endoscopic and open surgical methods. A third patient with a history
      consistent with PLF also underwent dual assessment. Endoscopic exploration of the
      middle ear was performed through a myringotomy and, immediately after, by
      elevation of a tympanotomy flap. The endoscopic examinations were thorough yet
      revealed no evidence of perilymphatic fistula; however, the surgical approaches
      revealed pooling in the oval windows consistent with perilymphatic fistula. These
      findings were video documented. Recurrent and primary fistulas may be the result
      of artifact, such as injected anesthetic agents and transudates introduced during
      surgical explorations, which may interfere with an accurate diagnosis of
      perilymphatic fistula. Endoscopy of the middle ear is recommended as one method
      to minimize errors in diagnosis.

PMID- 8572085
TI  - Static stabilometry, transcranial Doppler, and single photon emission computed
      tomography in patients with central dizziness.
AB  - Previous studies have found that transcranial doppler (TCD) and single photon
      emission computed tomography (SPECT) are effective means of diagnosing cerebral
      blood flow disorders in patients with central dizziness whose etiology was
      unknown by standard audiologic and/or vestibular assessment techniques. Also,
      static stabilometry, which measures a person's standing center of pressure (COP)
      movements, has been used to distinguish between patients with central neurologic
      and peripheral vestibular disorders. The purpose of this retrospective study was
      to examine the relation between TCD, SPECT, and stabilometry in patients with
      central dizziness attributable to cerebral blood flow disorders. Stabilometry
      testing was conducted on 50 normal subjects and 31 subjects with dizziness, the
      latter group consisting of persons with cerebral dysautoregulation, migraines,
      and unknown etiology with negative or positive SPECT results. The results
      indicated that patients with cerebral dysautoregulation were not significantly
      different from normal subjects or the other three groups in their COP movements.
      The other three groups exhibited significantly higher COP movements than the
      normal subjects, particularly when visual inputs were compromised. Patients with
      negative SPECT results were significantly different in their COP movements from
      the other three groups of subjects with dizziness. These results suggest that the
      pattern of COP movements may be useful in identifying patients with postural
      dysfunctions whose etiology may then be detected by TCD and SPECT.

PMID- 8572086
TI  - Ineraid cochlear implant in the ossified cochlea: surgical techniques and
      results.
AB  - Extensive ossification of the cochlea is a common finding in patients with total
      deafness caused by meningitis, labyrinthitis, or otosclerosis. When the cochlea
      is totally ossified, the prognosis for achieving free-running speech without lip
      reading is poor. However, subtotal ossification with residual cochlear patency in
      the upper basal turn, the middle turn, or the apical turn can be maximally
      exploited by selective insertion of electrodes. Results can be surprisingly
      adequate in spite of the poor anatomic conditions. Computed tomography and
      exploratory cochleotomy, in which electrically evoked auditory brainstem
      responses are elicited and recorded by intracochlear stimulation are good
      diagnostic indicators of ossification and residual auditory nerve excitability.
      "Apical cochleostomy" is an adequate procedure to help penetrate the basal turn
      in retrograde insertion of the cochlear implant electrode array. Results of this
      study indicate that the surgical technique and placement of the Ineraid electrode
      array play a major role in the ability of the patient to achieve understanding of
      free-running speech.

PMID- 8572087
TI  - Facial nerve stimulation after successful multichannel cochlear implantation.
AB  - Postoperative rehabilitation after cochlear implantation may be difficult and
      frustrating for both patient and audiologist. The occurrence of facial nerve
      stimulation with associated twitching and discomfort can interfere with the
      rehabilitative process and be a cause of great concern to the patient. Such
      stimulation can occur at the time of initial "tune-up" or can be delayed by
      months or years. The incidence of postoperative facial nerve stimulation 109
      consecutive patients operated by the same surgeon over a period of 7 years is
      reviewed. Possible causes for immediate and delayed stimulation are discussed,
      and strategies at surgery are outlined. Rehabilitative techniques for dealing
      with facial nerve stimulation are reviewed.

PMID- 8572088
TI  - A model for long-term intracochlear administration of pharmacologic agents.
AB  - A technique is described that provides a method to study the effects of
      intracochlear pharmacologic agents on the degenerating auditory nerve. The model
      involves implanting a guinea pig with an osmotic minipump that allows slow
      perfusion of the cochlea over a period of hours to days with up to two water
      soluble substances. Neomycin and horseradish peroxidase, whose histopathologic
      effects on the cochlea are well known, are used in the present study to validate
      the efficacy of the system.

PMID- 8572089
TI  - Effect of endotoxin on cultured rat middle ear epithelium, rat meatal epidermis,
      and human keratinocytes.
AB  - Several factors seem to contribute to the series of events in the pathogenesis of
      otitis media and cholesteatoma. Endotoxin is likely to be one of these factors,
      since it has been found in human middle ear effusions and since injection of this
      substance into the middle ear, in animal experiments, gave rise to prominent
      reactions. Provoking of epithelial cells in vitro with endotoxin led to distinct
      cell responses that might be associated with cholesteatoma formation. In this
      study the effect of endotoxin on serially cultured rat middle ear epithelium, rat
      meatal epidermis, and human keratinocytes was investigated. Endotoxin strongly
      stimulated the proliferation of middle ear epithelium and human keratinocytes and
      inhibited that of meatal epidermis. Furthermore, endotoxin affected the
      morphology of the three types of tissue. Rat middle ear epithelium revealed
      epithelial cell tracks with interconnecting bridge-like structures protruding
      above the culture plane, whereas rat meatal epidermis showed increased terminal
      differentiation expressing large areas of blister-like structures detaching from
      the culture dish. Cross-linked envelope analysis of human keratinocytes showed an
      increased terminal differentiation that was morphologically confirmed but was not
      confirmed by cytokeratin analysis. The results of this study support the
      hypothesis that endotoxin may play an important role in the pathogenesis of
      otitis media and cholesteatoma.

PMID- 8572090
TI  - Predictability of recovery from Bell's palsy using evoked electromyography.
AB  - The role of surgery in the treatment of idiopathic facial paralysis (Bell's
      Palsy) has been the subject of much controversy. Some have advocated aggressive
      surgical therapy to prevent nerve injury based on evoked electromyography (EEMG)
      results. The present study analyzes the outcome of 23 patients who presented with
      Bell's palsy and were evaluated with EEMG. Of the 15 patients who showed greater
      than 90 percent compound action potential reduction in the affected side, a
      widely used criterion for surgical decompression of the facial nerve, almost half
      (47%) had normal to near-normal recovery, and only three (20%) had residual
      severe dysfunction. Results infer that patients who meet surgical criteria based
      on EEMG results but who do not undergo surgery do not show a greater morbidity.
      The authors conclude that conservative criteria should be used when recommending
      facial nerve decompression.

PMID- 8572092
TI  - Surgical treatment of difficult cerebrospinal fluid otorhinorrhea.
AB  - Cerebrospinal fluid (CSF) otorhinorrhea may be a result of infection, congenital
      abnormality, trauma, or it may be iatrogenic. Despite its etiology, most cases of
      CSF otorhinorrhea resolve spontaneously or with conservative management. For
      those instances where the leak does not resolve, a large variety of drainage,
      packing, and obliteration procedures have been developed in an attempt to stop
      the CSF drainage and prevent the development of meningitis. Seven cases are
      reviewed that resulted in complete control of the leak with minimal morbidity.
      The authors' approach to difficult cerebrospinal fluid otorhinorrhea is presented
      and described in detail.

PMID- 8572091
TI  - Effects of cranial irradiation on hearing acuity: a review of the literature.
AB  - Radiation therapy is effective in the treatment of various tumors of the head and
      neck. Clinical practice and published literature reveal contradictory opinions
      regarding the incidence, type, severity, and time of onset of hearing loss as a
      complication of radiation therapy. Review of animal and human studies highlights
      the paucity of scientifically defensible information. The available literature
      appears to support the contention that otitis media and sensorineural hearing
      loss can occur as complications during, or shortly following radiation therapy.
      However, there is little or no convincing evidence to support the notion that
      hearing loss developing several years following radiation is causally related to
      radiation therapy. Additional research is needed.

PMID- 8572093
TI  - Mastoidectomy reconstruction: management of the high facial ridge using
      hydroxylapatite implants.
AB  - A high facial ridge is a common feature of open cavity cases presenting for
      rehabilitation and was present in 25 percent of a series of 223 cases requiring
      such surgery. A precise scutumplasty and posterior wall repair is required for
      optimal results. Prior organic methods have been found to be time-consuming,
      difficult, or unreliable. Current wall prostheses are unsuited in shape to these
      limited defects. Reconstruction using semicircular porous hydroxylapatite ceramic
      attic defect plates, has proved simple and effective when combined with posterior
      wall repair using autograft cartilage or sheets of porous hydroxylapatite
      ceramic. Reconstruction results from this group were the best of the larger
      series. This was attributable to lesser preoperative pathology, precise scutum
      repair, and more reliable revascularization of the defect area. The last was
      partly owing to the smaller dimensions involved, but has been improved by
      enhanced blood supply from the use of the middle temporal flap.

PMID- 8572094
TI  - Determinants and impact of headache after acoustic neuroma surgery.
AB  - Headache after acoustic neuroma surgery is known to occur clinically, but has not
      been studied systematically until recently. In the present study, 155 patients
      were surveyed regarding their experience of headache and associated symptoms
      following resection of an acoustic neuroma: 73 percent (n = 98) of patients
      undergoing suboccipital resection of an acoustic neuroma and 53 percent (n = 8)
      of patients undergoing translabyrinthine resection of acoustic neuroma complained
      of headache following surgery. The average pain intensity was greater for the
      suboccipital approach. Only 9 percent (n = 14) reported troublesome or frequent
      headaches preoperatively. Headache was described most often as tension type, with
      episodic acute exacerbations mimicking migraine. Clinical observations suggest
      that most patients are treated successfully with various combinations of
      reassurance, tricyclic antidepressants, nonsteroidal anti-inflammatory
      medications, trigger-point injections, adjunctive stress management techniques
      (relaxation), and physical therapy. The impact of recurrent headache on work and
      recreational function is notable. Several possible pathophysiological and
      biopsychosocial models are proposed to account for the prevalent headache
      problem. Although spontaneous resolution usually occurs over time, additional
      study is needed to determine the natural history of postoperative headache once
      it occurs.

PMID- 8572095
TI  - Bipolar recording of the cochlear nerve action potentials during cerebellopontine
      angle surgery.
AB  - A technique of bipolar recording of the cochlear nerve compound action potentials
      (CAPs) to make identification and preservation of the cochlear nerve easier
      during cerebellopontine angle surgery is described. Four patients, aged 32 to 65
      years, with acoustic tumors smaller than 2 mm and serviceable hearing,
      participated in the study. To investigate the resolution power of bipolar CAP
      recordings, a pilot study had been performed in a group of four patients
      submitted to vestibular neurectomy. Two silver electrodes insulated by Teflon up
      to the exposed ends were utilized for bipolar recording of the CAPs. They were
      twisted with each other and the distance between the two electrode tips could be
      varied from 0.3 to 0.7 mm. Rarefying polarity clicks (31/s) at 100 to 125 dB SPL
      were utilized as stimuli. Bipolar recording from the eight nerve was extremely
      selective: a good response was obtained only when the electrode was positioned on
      the cochlear portion of the eighth nerve. No response was present when the
      electrode was placed on the vestibular nerve and on the tumor. Frequent probing
      of tumor and eighth nerve with the bipolar recording electrode during acoustic
      neuroma removal facilitated the task of identifying the cochlear nerve and
      allowed its preservation in all patients.

PMID- 8572096
TI  - Long-term results after stapedectomy versus stapedotomy.
AB  - In a retrospective study postoperative hearing results after stapedotomy were
      compared with those after stapedectomy. Of 117 patients suffering from
      otosclerosis, 93 percent were primarily successfully operated between 1980 and
      1990 in the ENT department of the University of Vienna. Long-term results from 35
      stapedotomies and 22 stapedectomies were compared. Stapedotomy gave better
      results for high frequencies than stapedectomy. Whereas after stapedotomy no case
      of hearing loss could be observed, the incidence of anacusis after stapedectomy
      was 1.7 percent. Therefore, it is concluded that stapedotomy should be the
      preferred surgical technique in the treatment of otosclerosis.

PMID- 8572097
TI  - Osteoma of the malleus.
AB  - Osteomas of the temporal bone are benign neoplasms that may be encountered by
      otolaryngologists. Clinically they should be distinguished from exostoses, which
      involve the external auditory meatus and are a well recognized entity. Osteomas
      involving the middle ear and ossicles are extremely rare. There is only one case
      report in the literature of an osteoma involving an ossicle and in that patient,
      who presented with conductive loss, the incus was involved. The present report
      presents a 48-year-old white male, who on routine examination was found to have a
      mass in his left tympanic membrane. Under local anesthesia the mass was totally
      excised, after it had been separated from the umbo. Histopathologic sections of
      the mass revealed a benign osteoma. A brief review of osteomas and exostoses of
      the temporal bone is presented.

PMID- 8572098
TI  - Facial nerve outcome in acoustic tumor surgery.
AB  - Seventy-three procedures involving 70 acoustic tumors were carried out over 3
      years. The majority of tumors (65) were removed by the translabyrinthine
      approach. Tumor size ranged from 0.5 through 5.0 cm. All patients underwent
      intraoperative facial nerve monitoring: 22 patients developed immediate facial
      palsy (House-Brackmann grades II-VI); 11 patients recovered completely; 11
      patients (15.7%) had persistent paralysis. The incidence of long-term, poor
      outcome (H-B grade IV-VI) was 5.7 percent. The overall incidence of facial palsy
      was not found to be related to tumor size; however, facial paralysis associated
      with large tumors exhibited a poorer House-Brackmann grade compared to small and
      medium lesions. The use of intraoperative facial monitoring has enhanced the
      surgeon's ability to preserve facial nerve function by reducing the overall
      incidence of postoperative facial paralysis.

PMID- 8572099
TI  - The ethics of cochlear implants in young children.

PMID- 8572100
TI  - Intraoperative facial nerve monitoring in chronic ear surgery: a resident
      training experience.

PMID- 8572101
TI  - Temporal bone fracture, facial paralysis, only hearing ear: management.

PMID- 8572102
TI  - Conductive hearing loss secondary to a schwannoma involving the middle ear with
      normal facial function in a 69-year-old.

PMID- 8572103
TI  - Eye spasm following Bell's palsy.

PMID- 8572104
TI  - Facial paralysis in children.

PMID- 8572105
TI  - Results of multichannel cochlear implants in congenital and acquired prelingual
      deafness in children: five-year follow-up.
AB  - Postlingually deafened children, using multichannel cochlear implants, have
      achieved substantial improvement in their speech perception abilities and, in
      many instances, the results are better than in postlingually deafened adults. It
      has been suggested that children with prelingually acquired and congenital
      deafness would not receive similar benefits, since they have not developed an
      auditory memory. The purpose of this study is to analyze the speech perception
      and production performance over time of prelingually deafened children who have
      been using a multichannel cochlear implant for 1-5 years. Preliminary results
      comparing the effects of age at implantation and etiology of deafness on
      performance are also examined.

PMID- 8572106
TI  - Evaluation of a new spectral peak coding strategy for the Nucleus 22 Channel
      Cochlear Implant System.
AB  - Sixty-three postlinguistically deaf adults from four English-speaking countries
      participated in a 17-week field study of performance with a new speech coding
      strategy, Spectral Peak (SPEAK), and the most widely used strategy, Multipeak
      (MPEAK), both of which are implemented on wearable speech processors of the
      Nucleus 22 Channel Cochlear Implant System; MPEAK is a feature-extraction
      strategy, whereas SPEAK is a filterbank strategy. Subjects' performance was
      evaluated with an experimental design in which use of each strategy was reversed
      and replicated (ABAB). Average scores for speech tests presented sound-only at 70
      dB SPL were higher with the SPEAK strategy than with the MPEAK strategy. For
      tests in quiet, mean scores for medial vowels were 74.8 percent versus 70.1
      percent; for medial consonants, 68.6 percent versus 56.6 percent; for
      monosyllabic words, 33.8 percent versus 24.6 percent; and for sentences, 77.5
      percent versus 67.4 percent. For tests in noise, mean scores for Four-Choice
      Spondees at +10 and +5 dB signal-to-noise ratio (S/N) were 88.5 percent versus
      73.6 percent and 80.1 percent versus 62.3 percent, respectively; and for
      sentences at +15 dB, +10, and +5 dB S/N, 66.5 percent versus 43.4 percent, 61.5
      percent versus 37.1 percent, and 60.4 percent versus 31.7 percent, respectively.
      Subjects showed marked improvement in recognition of sentences in noise with the
      new SPEAK filterbank strategy. These results agree closely with subjects'
      responses to a questionnaire on which approximately 80 percent reported they
      heard best with the SPEAK strategy for everyday listening situations.

PMID- 8572108
TI  - Audio vestibular testing--technology versus clinical value.

PMID- 8572107
TI  - Long-term results of early cochlear implantation in congenitally and prelingually
      deafened children.
AB  - Cochlear implants have been shown to improve the speech perception and production
      skills in children. Data are available on congenitally and prelingually deafened
      children who were implanted at an older age, but data on children implanted below
      the age of 3 years are scarce. The present study examines the benefits obtained
      with early implantation of the young deaf child. Fourteen congenitally or
      prelingually profoundly hearing-impaired children were implanted before the age
      of 3 years, with the Nucleus multichannel cochlear prosthesis, and followed for 2
      5 years. Results indicate an overall improvement in the perception of all aspects
      of the speech signal in the auditory-only condition with the cochlear implant.
      All the children use oral language as their primary mode of communication and
      attend regular schools. Based on the results of this investigation, the authors
      conclude that implantation of the young deaf child is beneficial to the
      development of auditory perceptual skills.

PMID- 8572109
TI  - Reporting operative hearing results: does choice of outcome measure make a
      difference?
AB  - Choice of outcome measure in reporting hearing results following otologic
      surgery, including the frequencies used and use of pre- or postoperative bone
      thresholds, varies from author to author. In this study, data from 550 ossicular
      reconstruction and pediatric tympanoplasty surgery patients were used to generate
      a variety of outcome measures, including pure-tone thresholds for frequencies
      from 0.5 kHz to 8 kHz and different frequency combination pure-tone averages
      (PTAs) and air-bone gaps. There were no significant differences between mean pre-
      and postoperative bone conduction thresholds for any of the frequencies from 0.5
      to 4 kHz nor for a PTA of 1, 2, and 4 kHz. Mean postoperative air-bone gap
      differed by no more than 2 dB across six different frequency combination PTAs. If
      "success" is defined as a postoperative air-bone gap of less than 20 dB, the
      largest difference in success rate across the six frequency combinations was 5%.
      There was also little difference in mean postoperative air conduction PTAs for
      any of the combinations that include frequencies through 4 kHz. Choice of a more
      conservative or more liberal definition of success was more important than
      whether air-bone gap or air conduction PTA was used. The authors recommend that a
      standard reporting procedure be adopted that ensures presentation of the results
      in a format such that more direct comparisons can be made within the published
      literature.

PMID- 8572110
TI  - Efficacy of auditory brainstem response as a screening test for small acoustic
      neuromas.
AB  - Auditory brainstem response (ABR) has been advocated as a high sensitivity
      screening test for acoustic neuroma. With the advent of magnetic resonance
      imaging (MRI), smaller size acoustic neuromas are now detectable. A prospective
      trial was performed to determine the sensitivity of ABR in diagnosing small
      acoustic neuromas. One hundred five randomly selected patients with surgically
      proved acoustic neuromas underwent preoperative ABR tests within 2 months of
      their surgery. Patients with a histologic diagnosis other than acoustic neuroma
      were excluded from this study. A test was considered abnormal when the interaural
      wave I-V latency difference was greater than 0.2 ms, the absolute wave V latency
      was abnormally prolonged, or there was abnormal or absent waveform morphology. Of
      the 105 patients tested 92 (87.6%) had abnormal ABR test, and 13 (12.4%) had
      completely normal waveforms and wave latencies. Eighteen patients had tumors over
      2 cm in total diameter. Of these, 12 were 2.5 cm or larger and 6 were between 2.1
      and 2.4 cm. All of these 18 patients had abnormal ABR tests. Of the 29 patients
      with tumors 1.6-2.0 cm in size, 25 (86%) had abnormal ABRs. In the 1.0-1.5 cm
      diameter range there were 45 patients who underwent a preoperative ABR. Of these,
      40 (89%) had abnormal ABRs. Of 13 patients with tumors 9 mm or smaller, only 9
      (69%) had abnormal ABR test (p < .05). Thus, it appears that ABR sensitivity
      decreases with tumor size and is particularly inadequate for tumors of less than
      1 cm in diameter. The authors conclude that ABR is not a good screening test for
      smaller acoustic neuromas and recommend MRI for patients with suspected acoustic
      neuroma.

PMID- 8572111
TI  - Ultrastructural findings in the vestibular end-organs of AIDS cases.
AB  - Neurotologic manifestations are apparent in human immunodeficiency virus (HIV)
      infection, but are poorly understood. Symptoms related to the vestibular system
      include episodes of vertigo, imbalance, ataxia, and nausea. Although patients
      present more often with hearing impairment, vestibular complaints are described
      and electrophysiologic studies indicate vestibular dysfunction in HIV-infected
      patients. Whether the disease involvement includes the central, or the peripheral
      nervous system has not been established. Ultrastructural analysis of vestibular
      end-organs obtained from HIV autopsy cases revealed pathologic changes in the
      labyrinth wall, the epithelial lining, and the receptor maculae and cristae.
      Cytologic changes in hair cells included inclusion bodies, viral-like particles,
      and hair bundle malformations. Epithelial lining cells, supporting cells, and
      connective tissue cells had inclusions and viral-like particles. These findings
      are consistent with those of a previous cochlear study demonstrating
      intracellular viral-like particles with the morphologic characteristics of HIV.
      Further cytologic evaluation of decalcified temporal bones and
      immunohistochemical analysis of freshly harvested HIV-infected temporal bones may
      provide further insight into the pathogenesis of viral-induced hearing loss and
      vestibular impairment.

PMID- 8572112
TI  - Adenomatous lesions of the temporal bone immunohistochemical analysis and
      theories of histogenesis.
AB  - Adenomatous lesions of the temporal bone represent a diverse group of neoplasms.
      At least three histopathologic patterns have been described: glandular; ribbon
      like, or "festooning;" and aggressive papillary. Combinations of glandular and
      ribbon-like histologies in the same lesion are not uncommon. The glandular and
      ribbon-like histologies have been associated with carcinoid tumors, and the
      aggressive papillary tumor has been considered a separate entity. Recently, the
      endolymphatic sac has been proposed as the site of origin of the aggressive
      papillary lesions. Previous reports have described neuroendocrine properties with
      characteristics embracing the three histologic types. The authors postulate that
      the neural crest is the site of origin of this unusual group of neoplasms.
      Immunohistochemical analysis on the pathologic specimens of patients with
      adenomatous lesions of the temporal bone was performed to test this hypothesis.
      From 1975 to 1992 seven patients were treated at the Cleveland Clinic Foundation
      with a diagnosis of middle ear adenoma. A panel of special stains for
      neuroectodermal markers, including synaptophysin, chromogranin, neuron specific
      enolase, calcitonin, and serotonin was used on the paraffin-embedded formalin
      fixed specimens. Three lesions were also evaluated by electron microscopy, all
      demonstrating dense core, intracytoplasmic granules. Three ribbon-like tumors
      were positive for synaptophysin and chromogranin, and two of these were positive
      for serotonin. One glandular tumor was positive for synaptophysin, and an
      aggressive papillary tumor was positive for synaptophysin and neuron specific
      enolase. An additional papillary tumor was referred following a third recurrence
      without accompanying immunohistochemical data. Cholesteatoma-like material was
      identified with a few glandular cells interspersed, all negative by
      immunohistochemical evaluation. The seventh specimen, initially diagnosed as
      papillary adenoma on light microscopy, was not studied by the aforementioned
      stains, and was later identified as a papilloma of sinonasal origin. The neural
      crest gives rise to pluripotential stem cells with widespread anatomic
      distribution, including the temporal bone. Because immunomarkers used in this
      study are specific for neuroectodermal differentiation, results suggest that
      temporal bone adenomas have neuroendocrine characteristics and could be derived
      from the specialized neuroectoderm of the neural crest.

PMID- 8572113
TI  - High resolution two-dimensional electrophoresis: technique and potential
      applicability to the study of inner ear disease.
AB  - Technologic progress in two-dimensional polyacrylamide gel electrophoresis (2-D
      Page), in combination with immunoblotting, amino acid sequencing, and computer
      assisted image analysis, allowed establishment of human body fluid and tissue
      "reference maps," which in turn enabled meaningful comparison of data from
      various clinical and research centers. Altered protein profiles have been
      observed in plasma/serum, cerebrospinal fluid, urine, and other body fluids in
      numerous systemic or localized pathologic entities. Human perilymph, obtained
      during ear surgery or post mortem, exhibits a protein profile differing from
      plasma in several ways. Most interesting are the extremely high levels of high
      density lipoprotein-associated proteins, a group of proteins thought to play a
      role in atherosclerosis, nerve damage/regeneration, chronic inflammation, and
      Alzheimer's disease, among others. A technique is described for collection and
      analysis of human perilymph, using a state-of-the-art standardized 2-D Page
      technique. It is expected that, as in other body fluids, disease-specific protein
      patterns will be identified. With the possible exception of presumed
      perilymphatic fistula, it is not envisioned that analysis of perilymph will be
      used for diagnostic purposes but rather as an aid for the elucidation of the
      mechanisms underlying inner ear disease, whether localized or as part of systemic
      alterations.

PMID- 8572114
TI  - Endoscope-assisted ear surgery.
AB  - Endoscopes deliver the otologic surgeon's view into the temporal bone to provide
      rapid access to its intricate recesses. The attic, sinus tympani, facial recess,
      hypotympanum, internal auditory canal, and other recesses are immediately
      visualized with angled endoscopes, using minimal exposure without the time
      consuming removal of overlying bone. This report presents results of 32 otologic
      and neurotologic operations, performed since 1993, that incorporated endoscope
      guided dissection as a principal part of the procedure to reduce incision size,
      exposure width, and operative time, or to access areas otherwise inaccessible.
      Included are endoscopic excision of acquired cholesteatoma without mastoidectomy,
      second-look mastoid procedures, mastoidectomy for biopsy (performed entirely
      endoscopically), and acoustic neuroma dissection from the lateral internal
      auditory canal. Endoscopic ear surgery is a valuable adjunct to conventional
      surgical techniques that require wider exposures and are limited to the direct
      line of sight.

PMID- 8572115
TI  - Cochlear implant device failure: diagnosis and management.
AB  - Complete, irreversible failure of the implanted receiver-stimulator of the
      Cochlear Corporation multichannel implant are relatively rare. However, as the
      implanted patient population grows, malfunctions may be expected. From the over
      200 patients implanted at the University of Michigan Medical Center, 6 patients
      with a complete and irreversible cochlear implant receiver-stimulator failure
      have been identified and treated. This represents a 3% failure rate. The amount
      of time between initial implantation and device failure ranged from 6 months to
      3.5 years. Determination of device failure was made using psychophysical,
      electrophysiologic, and averaged electrode voltage measurements. The measurement
      of the average electrode voltages proved to be useful in determining the
      condition of the implant. Physiologic changes causing reduced electrical
      excitability were ruled out using psychophysical or electrophysiologic promontory
      testing. All patients were successfully explanted and reimplanted.

PMID- 8572116
TI  - Autologous fibrin glue in the prevention of cerebrospinal fluid leak following
      acoustic neuroma surgery.
AB  - Postoperative cerebrospinal fluid (CSF) leak is a serious complication of
      acoustic neuroma surgery. The authors retrospectively reviewed the charts of 492
      patients who underwent acoustic neuroma surgery to determine the efficacy of
      fibrin glue in preventing postoperative CSF leak. Thirteen of 92 patients (14%)
      undergoing retrosigmoid/transmeatal surgery experienced CSF leak when fibrin glue
      was used; 29 of 199 patients (15%) when it was not used. Nineteen of 85 patients
      (22%) experienced CSF leak when fibrin glue was used following translabyrinthine
      surgery; 23 of 116 patients (20%) when it was not used. No decrease was noted in
      the incidence of CSF leak following acoustic neuroma surgery with the use of
      autologous fibrin glue.

PMID- 8572117
TI  - Aural tuberculosis.
AB  - Since the advent of antituberculous therapy, tuberculosis of the ear has
      decreased in incidence; but of late, cases of both pulmonary and otologic
      tuberculosis are on the rise. In addition, the treatment of aural tuberculosis is
      now more difficult due to resistance to one or more of the routinely used
      antituberculous pharmacotherapeutic agents. Urban areas and selected populations
      have been particularly endangered by the re-emergence of this disease. In light
      of this developing situation, three cases of aural tuberculous infections are
      presented. Typical and atypical presentations of the disease, including history,
      signs, symptoms, and radiographic findings are discussed, as are treatment
      options. The importance of aural tuberculosis as part of the general increase in
      incidence and resistance of the disease is examined.

PMID- 8572118
TI  - Current status of cochlear implants in Latin America.
AB  - In recent years there has been sufficient clinical evidence gathered to show that
      cochlear implants can benefit a large number of postlingually and prelingually
      profoundly deaf patients who could not be helped with conventional hearing aids.
      The number of implanted patients is increasing rapidly around the world in spite
      of the diverse difficulties in diagnostic, surgical, and rehabilitation
      procedures involved in this new technology and the controversy among some
      otologists. Cochlear implant programs started in Latin America more than 10 years
      ago, and lately the number of cochlear implant teams and implanted patients have
      increased rapidly. It is the aim of this report to present the results of a
      recently completed survey regarding the current status of cochlear implant
      surgery and rehabilitation in Latin America.

PMID- 8572119
TI  - Cochlear pathology following reimplantation of a multichannel scala tympani
      electrode array in the macaque.
AB  - The histopathologic consequence of removing and reimplanting intracochlear
      electrode arrays on residual auditory nerve fibers is an important issue when
      evaluating the safety of cochlear prostheses. The authors have examined this
      issue by implanting multichannel intracochlear electrodes in macaque monkeys.
      Macaques were selected because of the similarity of the surgical technique used
      to insert electrodes into the cochlea compared to that in humans, in particular
      the ability to insert the arrays into the upper basal turn. Five macaques were
      bilaterally implanted with the Melbourne/Cochlear banded electrode array.
      Following a minimum implant period of 5 months, the electrode array on one side
      of each animal was removed and another immediately implanted. The animals were
      sacrificed a minimum of 5 months following the reinsertion procedure, and the
      cochleas prepared for histopathologic analysis. Long-term implantation of the
      electrode resulted in a relatively mild tissue response within the cochlea.
      Results also showed that inner and outer hair cell survival, although
      significantly reduced adjacent to the array, was normal in 8 of the 10 cochleas
      apicalward. Moreover, the electrode reinsertion procedure did not appear to
      adversely affect this apical hair cell population. Significant new bone formation
      was frequently observed in both control and reimplanted cochleas close to the
      electrode fenestration site and was associated with trauma to the endosteum
      and/or the introduction of bone chips into the cochlea at the time of surgery.
      Electrode insertion trauma, involving the osseous spiral lamina or basilar
      membrane, was more commonly observed in reimplanted cochleas. This damage was
      usually restricted to the lower basal turn and resulted in a more extensive
      ganglion cell loss. Finally, in a number of cochleas part of the electrode array
      was located within the scala media or scala vestibuli. These electrodes did not
      appear to evoke a more extensive tissue response or result in more extensive
      neural degeneration compared with electrodes located within the scala tympani. In
      conclusion, the present study has shown that the reimplantation of a multichannel
      scala, tympani electrode array can be achieved with minimal damage to the
      majority of cochlear structures. Increased insertion trauma, resulting in new
      bone formation and spiral ganglion cell loss, can occur in the lower basal turn
      in cases where the electrode entry point is difficult to identify due to
      proliferation of granulation and fibrous tissue.

PMID- 8572120
TI  - Interconnecting the posterior and middle cranial fossae for tumors that traverse
      Meckel's cave.
AB  - Meckel's cave is an avenue for tumor to spread between the posterior and middle
      cranial fossae. The most common neoplasms that traverse this channel are
      trigeminal schwannomas and meningiomas. The classic approach to address disease
      in both cranial fossae involves separate craniotomies. Recent innovations in
      skull base surgery have made it possible to perform a single opening with
      simultaneous exposure of the posterior and middle fossae, without undue brain
      retraction. Tumors with a large middle fossa component and a smaller posterior
      fossa portion are exposed via subtemporal craniotomy with petrosectomy and
      tentorium division. However, tumors with a large posterior fossa component and a
      smaller middle fossa portion in the setting of serviceable hearing are addressed
      with retrosigmoid craniotomy and petrosectomy. For bilobed tumors with
      substantial components in both fossae, subtemporal craniotomy combined with
      varying degrees of transtemporal petrosectomy and tentorium division is employed.
      The evolution of techniques to address tumors that traverse Meckel's cave is
      reviewed and a treatment algorithm is proposed.

PMID- 8572121
TI  - Comparison of tympanic membrane-recorded electrocochleography and the auditory
      brainstem response in threshold determination.
AB  - The purpose of this study was to evaluate the usefulness of electrocochleography
      (ECoG) recorded with a tympanic membrane electrode as an adjunctive measure to
      auditory brainstem response (ABR) in frequency-specific threshold estimation. In
      a group of 10 normally hearing and 10 sensorineural hearing-impaired subjects,
      ABR and ECoG were simultaneously recorded in response to tone-burst stimuli
      centered at 500, 1000, 2000, and 4000 Hz. At each frequency, stimulus intensity
      was reduced in 12-dB decrements from an initial level of 110 dB SPL until no
      replicable response could be discerned. Electrocochleography and ABR thresholds
      were determined at each frequency, and correlation to behavioral audiometric
      threshold was determined. Input/output functions were also computed. At 2000 and
      4000 Hz, both ABR and ECoG thresholds correlated with behavioral audiometric
      threshold. At 1000 Hz, ABR threshold correlated with behavioral audiometric
      threshold; ECoG did not. At 500 Hz, neither ABR nor ECoG threshold correlated
      with behavioral audiometric threshold. Input/output functions were steeper for
      ECoG than for ABR at all frequencies tested in the normally hearing group.

PMID- 8572122
TI  - Postural stability following mild head or whiplash injuries.
AB  - Studies of the sequelae of head injury suggest that cochlear and vestibular
      dysfunctions, comprise some of the most frequently reported delayed complications
      following head trauma. To date, little attention has been given to the relation
      between post-traumatic subjective symptoms of dizziness and the objective
      measures of postural stability or balance. The purpose of this study was to
      quantify the balance deficits in individuals who had developed symptoms of
      dizziness following mild head and whiplash injuries. The balance abilities of 29
      patients, who developed dizziness following some type of mild head or whiplash
      injury, were compared to those of 51 healthy symptom-free subjects. Balance was
      assessed by examining the center-of-pressure movements, in the anterior-posterior
      and medial-lateral directions, and the total movement displacement. The isolated
      contributions of visual and somatosensory inputs were estimated by comparing the
      magnitudes of the center-of-pressure movements for the various sensory
      conditions. Data were collected from three 30-second trials of each combination
      of three visual conditions (accurate, absent, and inaccurate) and two
      somatosensory conditions (accurate and inaccurate), with the patient standing on
      a fixed-force platform. Univariate analyses of variance indicated that the group
      with head injury, compared to the control group, exhibited significantly greater
      anterior-posterior movements in four of the six sensory conditions and greater
      total movement displacement during the inaccurate vision/inaccurate
      somatosensation condition. These data suggest that patients who have sustained
      head or neck trauma exhibit increased reliance on accurate visual input and are
      unable to utilize vestibular orienting information to resolve conflicting
      information from the visual and somatosensory systems.

PMID- 8572123
TI  - Chronic tympanic membrane perforation: an animal model.
AB  - Acute perforations in the tympanic membranes (TM) of animals are not good models
      for assessment of materials used as graft membranes or of substances with the
      potential to activate tympanic membrane healing mechanisms for closing
      perforations. Most acute TM perforations heal spontaneously, in both animals and
      humans. Acute TM perforation models are not analogous to the pathologic human
      problem of long-standing TM perforation. Bilateral subtotal symmetric
      perforations, with each animal serving as its own control provide a suitable
      model. Fourteen dogs were operated. Subtotal perforation of TM in right ears were
      soaked with 2% glutaraldehyde to develop an animal model for persistent tympanic
      membrane perforation. Subtotal myringectomy was performed on left ears, without
      chemical treatment of the rim. Perforations were standardized in size. The
      healing pattern was evaluated weekly for a 15-week period. Six of the right ears
      and 14 of the left ears completely healed within 15 weeks. Statistically, the
      mean delay of closure was higher in the treated group than in the non-treated
      group, and the two groups were different according the closure rate criterion.
      Histologic analyses of persistent TM perforations and of healed cases were
      performed.

PMID- 8572124
TI  - Osteoinductive substances in middle ear surgery.
AB  - There have been a number of stages in the development of cholesteatoma surgery.
      After the introduction of the radical operation the disadvantages of this
      procedure led to the development of more conservative operative techniques, for
      example the anterior-posterior approach with preservation of the posterior wall
      of the external ear canal or the obliteration of the mastoid cavity with muscle
      flaps or various materials. The assumption that organic fragments of the bone
      enable certain unspecified mesenchymal cells to form bone led to this
      investigation. Allogenic bone matrix and gelatin were implanted in the
      epitympanic recess in 16 rabbits. The animals were sacrificed 2, 4, and 8 weeks
      after the operation and the temporal bones were examined histologically. Both the
      implanted substances led to the formation of new bone in the epitympanic recess
      in rabbits. The newly formed bone bonded itself with the bony wall of the
      epitympanic recess. The existence of foreign body giant cells could not be
      verified. Perhaps the difficulties involved in treating cholesteatomas could be
      solved with osteoinductive substances.

PMID- 8572125
TI  - Surgical techniques for insertion of a multi-electrode implant into a
      postmeningitic ossified cochlea.
AB  - Severe ossification within the cochlea occurs in more than 20% of children
      deafened by meningitis. A multi-electrode cochlear implant can dramatically
      restore useful hearing to such children, providing it can be inserted
      satisfactorily within the cochlea. Various surgical techniques for cochlear
      implantation into an ossifying cochlea are discussed. Partial ossification often
      can be negotiated by clearing the new bone from the scala tympani or by inserting
      the array through the scala vestibuli. Total ossification is not a
      contraindication to the use of a multi-electrode cochlear implant. A method of
      drilling out the basal cochlear turn without removal of the overlying promontory
      is proposed. The results of "inlay" insertion into a totally ossified cochlea are
      evaluated in five ears.

PMID- 8572126
TI  - Traumatic endolymphatic hydrops.
AB  - Traumatic endolymphatic hydrops is an accumulation of endolymph in the cochlear
      duct caused by traumatic insult. The causative mechanisms are: (1) fistulization
      of the bony labyrinth, which causes a disturbance in the normal perilymph
      endolymph pressure relationship; (2) direct injury to the membranous labyrinth,
      which may be just a collection of fluid in the cochlear duct from irritation,
      resulting in endolymphatic hydrops that may not be progressive and may subside in
      a short period of time after injury and hearing loss may occur; and (3) injury to
      the endolymphatic fluid drainage system, including a temporal bone fracture in
      which the fissure happens to extend through the vestibular aqueduct, causing
      fibro-osseous blockage of the endolymphatic duct and surgical injury to the
      saccule with obstruction of the longitudinal flow of endolymph, resulting in
      endolymphatic hydrops that may be delayed in onset and is usually persistent. The
      diagnosis of traumatic endolymphatic hydrops is made by a history of trauma, such
      as barotrauma, a blow to the head, or perhaps a previous ear operation, such as
      stapedectomy; the presence of typical symptoms of endolymphatic hydrops,
      including fullness, tinnitus, fluctuant hearing loss, and episodic vertigo; and
      an elevated negative summating potential and an increased summating
      potential:action potential ratio by electrocochleography. Three patients are
      presented to demonstrate this clinical entity.

PMID- 8572127
TI  - Air-bone gap in patients with X-linked stapes gusher syndrome.
AB  - It is often possible to elicit the stapedius reflex in patients suffering from
      recessive X-linked progressive mixed deafness syndrome with stapes gusher. The
      presence of an air-bone gap in the audiogram and the ability to elicit the
      stapedius reflex are conflicting. Measurements were performed on two patients who
      were suffering from this syndrome, to establish whether the hearing loss was of
      the mixed or purely sensorineural type. It was argued that, owing to congenital
      malformations, the audiovestibular system might act as a more than normally
      efficient transducer, to convert skull vibrations into inner ear fluid motions,
      leading to bone conduction thresholds that are better than expected. The results
      of tone and speech audiometry, stapedius reflex measurements, and brainstem
      evoked response audiometry in this study showed a pattern similar to that
      generally seen in patients with purely sensorineural hearing loss. This supports
      the hypothesis that the air-bone gap in the audiogram does not have the usual
      significance of a conductive hearing loss component.

PMID- 8572128
TI  - Julius Lempert and the fenestration operation.

PMID- 8572129
TI  - News from the National Institute on Deafness and other Communication Disorders.

PMID- 8572130
TI  - Facial paralysis at birth: medicolegal and clinical implications.

PMID- 8572131
TI  - Surgery of congenital aural atresia.
AB  - The treatment of congenital aural atresia has changed in recent years. Better
      imaging capabilities, the development of tympanoplasty techniques, modification
      of mastoid dissection, and facial nerve monitoring have resulted in greater
      patient benefit with less patient risk. Success rates continue to be high, and
      the incidence of complications has decreased. A series of cases was reported in
      1985, and now the authors review 92 congenital aural atresiaplasties performed
      over the following 9 years. Closure of the air-bone gap to less than 30 dB was
      achieved in 60% of primary surgeries and 54% of revisions. The most common
      complications were external auditory canal stenosis and lateralization of the
      tympanic membrane. External auditory canal stenosis due to bony regrowth was seen
      in 12% of primary cases and 11.5% of revisions; soft tissue stenosis was seen in
      10% of primaries and 4% of revisions. Tympanic membrane lateralization was seen
      in 9% of primary surgeries and in 15% of revisions. Carbon dioxide and argon
      lasers (HGM Medical Laboratories, Salt Lake City, Utah) and Merocel stenting
      wicks with split-thickness skin grafting were used to try to improve long-term
      hearing outcome and decrease postoperative external auditory canal stenosis. With
      meticulous surgical technique by an experienced otologic surgeon and
      appropriately selected patients, this problem can be managed effectively.

PMID- 8572132
TI  - Ossiculoplasty using the black hydroxylapatite hybrid ossicular replacement
      prostheses.
AB  - The problems of ossicular reconstruction in chronic ear surgery have led to the
      development of new ossicular replacement prostheses. Improvements in
      biocompatibility and design led to the development of hydroxylapatite hybrid
      (HaH) ossicular replacement prostheses. The senior author's (M.E.G.) experience
      with the Black HaH prostheses is reviewed. Sixty cases are grouped by procedure
      and prosthesis (19 TORPs and 41 PORPs) with a minimum follow-up of 1 year.
      Audiometric data are analyzed to determine the success rate in air-bone gap
      closure. Complication and extrusion rates are reviewed. These results are
      compared against those obtained using other prostheses using similar criteria,
      and this report serves as a follow-up on a previous paper on this subject by the
      senior author.

PMID- 8572133
TI  - Safety of silver oxide-impregnated silastic tympanostomy tubes.
AB  - Otorrhea occurs after the insertion of tympanostomy tubes in as many as 50% of
      ears. Although topical antibiotic solutions minimize otorrhea in the immediate
      postoperative period, recurrent otorrhea is sometimes a clinical problem. The
      antimicrobial effects of silver oxide when impregnated into a tympanostomy tube
      may decrease the incidence of recurrent otorrhea. This study demonstrates that
      silver oxide-impregnated silicone elastomer is well tolerated within the middle
      ear of gerbils when implanted for 1 year, and the tissue reaction is no more than
      silicon elastomer without silver oxide. When applied directly to the round window
      of guinea pigs, there was no evidence of ototoxicity of silver oxide as measured
      by electrocochleography (N-1 thresholds) and cytocochleography (hair cell
      counts). These animal studies indicate that silver oxide-impregnated silicone
      elastomeric tympanostomy tubes may be used safely in clinical trials to determine
      efficacy.

PMID- 8572134
TI  - Paroxysmal positional vertigo: an overview and the deposits repositioning
      maneuver.
AB  - In a retrospective live study, electronystagmographic (ENG) recordings in
      patients (n = 526) suffering from paroxysmal positional vertigo (PPV) of the
      posterior semicircular canal were divided into group I (n = 425) and group II (n
      = 101), depending on whether the vertigo could or could not be elicited at the
      time of recording. There was no statistical difference between the two groups for
      (1) the ipsilateral (fast phase toward the affected side) or the contralateral
      positional nystagmus (excluding the nystagmus recorded during the paroxysm) or
      (2) the bithermal caloric labyrinthine or directional preponderance; nor within
      each group for (1) the ipsilateral versus the contralateral positional nystagmus
      or (2) the ipsilateral (on the affected side) versus the contralateral
      labyrinthine and/or directional preponderance. In a prospective study, the
      deposits repositioning maneuver (DRM) was attempted in 41 patients. One day post
      treatment patients felt no change, better, or free of vertigo. Most patients, who
      developed nystagmus in the final DRM head position similar to the nystagmus
      observed in the provocative head position had a better outcome. It is concluded
      that ENG recordings do not contribute to the diagnosis of PPV. The type of
      observed nystagmus in the final DRM head position is frequently an outcome
      predictor. Following the DRM, failures and/or recurrences are to be expected.

PMID- 8572135
TI  - Temporal bone histopathology of cisplatin ototoxicity.
AB  - Cisplatin (cis-diamminedichloroplatinum II) is a potent chemotherapeutic agent
      that is useful in the treatment of a variety of malignancies. Ototoxicity is a
      well-known adverse side effect of this drug and has been widely described in
      reports on clinical and animal studies. Few human temporal bone studies, however,
      have been performed for cisplatin ototoxicity. This report presents four cases of
      cisplatin ototoxicity in patients from whom temporal bone specimens with minimal
      post-mortem autolysis were obtained at autopsy. All patients received between 1
      and 6 cycles of cisplatin with doses ranging from 100 to 165 mg/M2 per cycle.
      None of the patients received significant amounts of aminoglycosides or loop
      diuretics. Histopathologic changes included loss of inner and outer hair cells in
      the basal turn of the cochlea, degeneration of the stria vascularis, and a
      significant decrease in spiral ganglion cells predominantly in the upper turns.

PMID- 8572136
TI  - Sinus tympani: anatomic considerations, computed tomography, and a discussion of
      the retrofacial approach for removal of disease.
AB  - Surgical access to the sinus tympani remains a challenge for otologic surgeons.
      Usually, the retrotympanum is approached through the middle ear in an anterior to
      posterior direction during chronic ear surgery. Whether this is via a posterior
      tympanotomy or after canal wall down tympanomastoidectomy, visualization of the
      most posterior recess of the sinus tympani is often inadequate. The purpose of
      this investigation is two fold: (1) to describe the highly variable anatomy of
      the posterior tympanic cavity and (2) to review the retrofacial approach to the
      sinus tympani. Histologic sections, cadaver dissections, and diagrammatic
      illustrations are combined with computed tomographic (CT) imaging to provide a
      three-dimensional understanding of the sinus tympani and adjacent labyrinthine
      structures. Viewed from the mastoid, the anatomic structures that define the
      boundaries of the retrofacial approach include the facial nerve and stapedius
      muscle laterally, the lateral semicircular canal superiorly, the posterior
      semicircular canal posteromedially, the vestibule anteromedially, and the jugular
      bulb inferiorly. When the sinus tympani is well developed, saucerization within
      these boundaries gives wide access into the sinus and round window niche. The
      authors suggest that preoperative imaging can select patients who are candidates
      for a retrofacial approach to expose and remove disease in the sinus tympani.
      Contraindications to this approach include axial CT image measurements showing a
      contracted space between the posterior semicircular canal and the medial aspect
      of the facial nerve, lack of posterior expansion of the sinus tympani, and in
      cases where these measurements are marginal, the presence of a high jugular bulb
      or anteriorly positioned sigmoid sinus.

PMID- 8572137
TI  - Herniation of the temporomandibular joint into the external auditory canal: a
      complication of otologic surgery.
AB  - Herniation of the temporomandibular joint into the external auditory canal has
      been reported as a result of trauma, neoplasia, infection, inflammatory
      processes, or developmental malformations. This paper reviews the intimate
      relation of the temporomandibular joint to the temporal bone as well as the
      literature describing temporomandibular joint herniation into the external
      auditory canal. Four cases of temporomandibular joint herniation into the
      external auditory canal resulting from otologic surgery are presented. Their
      characteristic location, clinical and radiographic findings are described and
      contrasted to previously reported cases. Despite striking displacement of the
      temporomandibular joint into the external auditory canal, there were no clinical
      symptoms referable to this finding. The absence of symptoms distinguished this
      postoperative etiology of temporomandibular joint herniation from other
      etiologies mentioned above.

PMID- 8572138
TI  - Delayed onset facial nerve dysfunction following acoustic neuroma surgery.
AB  - Delayed onset facial nerve dysfunction following acoustic neuroma surgery is an
      under-appreciated phenomenon. The authors have recently reviewed long-term (> 1
      year) facial nerve outcome in 129 patients who underwent acoustic neuroma removal
      with the aid of cranial nerve monitoring between 1986 and 1990. The facial nerve
      was anatomically preserved in 99.2% of the patients, and at one year, 90% of all
      the patients had House-Brackmann (H-B) grade I or II facial nerve function.
      Delayed onset worsening of facial nerve function was noted in 38 of 129 (29%)
      patients, most of which occurred in the first few postoperative days. The
      incidence increases to 41% (38 of 93) when corrected for those with immediate H-B
      grade VI weakness, and who therefore could not manifest further deterioration.
      The facial nerve function either deteriorated from normal to abnormal or
      increased in severity of weakness. Delayed facial palsy was not related to the
      size of tumor or the surgical approach. The most common occurrence was that of a
      patient with H-B grade I or II facial nerve function worsening to H-B grade VI in
      the postoperative period. The prognosis for recovery of facial nerve function
      following delayed palsy was excellent. In the majority of cases, the recovery was
      complete within the first 6 months without specific treatment. Comparable to the
      patients without delayed palsies, 89% (34 of 38) of the cases had H-B grade I or
      II and 97% (37 of 38) had H-B grade III or better facial nerve function at 1
      year. This review suggests a surprisingly high incidence of delayed facial palsy
      following acoustic neuroma surgery, which fortunately has an excellent prognosis
      for spontaneous recovery.

PMID- 8572139
TI  - Spontaneous cerebrospinal fluid otorrhea from defects of the temporal bone: a
      rare entity?
AB  - Cerebrospinal fluid (CSF) otorrhea is usually associated with a history of trauma
      or previous surgery. Spontaneous CSF otorrhea is uncommon. When such spontaneous
      CSF leakage occurs, it may be associated with dural herniation, with the
      production of conductive hearing loss from impingement on the ossicles. This type
      of leakage has characteristic findings which, if recognized, can lead to earlier
      diagnosis and avoidance of complications. A review of the world literature
      revealed 44 reported cases. This report presents the authors' experience with 12
      patients with spontaneous CSF leakage from temporal bone defects. This entity may
      be more prevalent than is reported. The differential diagnosis and management of
      CSF otorrhea (secondary to temporal bone defects) are discussed and
      representative cases are presented.

PMID- 8572140
TI  - Cranial neuropathy secondary to perineural spread of cutaneous malignancies.
AB  - Skin cancers of the head and neck are common lesions that rarely metastasize or
      invade cranial nerves. Perineural spread, when present, typically involves
      cranial nerves V and VII, because of their extensive subcutaneous distributions.
      Partial or complete facial palsy, facial hypesthesia, and/or pain may occur
      months to years after excision of a cutaneous malignancy and is often the first
      manifestation of regional metastasis. Too often, a history of facial skin cancer
      is not elicited in the evaluation of patients who present with fifth and/or
      seventh cranial nerve neuropathies. The initial yield from computerized
      tomography and magnetic resonance imaging is often limited, leaving most patients
      with the diagnosis of Bell's palsy. The authors herein present their experience
      with the diagnosis and management of seven patients who developed a fifth or
      seventh cranial nerve neuropathy an average of 13.4 months following "complete"
      excision of a regional skin cancer.

PMID- 8572141
TI  - Aggressive papillary tumors of the endolymphatic sac: clinical and tissue culture
      characteristics.
AB  - Aggressive papillary tumors of the temporal bone are neoplasms that were recently
      re-classified as tumors of the endolymphatic sac. They typically invade the
      mastoid bone and otic capsule and can grow into the petrous apex. The authors
      have treated three patients with this rare neoplasm and grown one of the tumors
      in tissue culture. This report reviews the clinical presentation in the three
      patients and the immunohistochemical staining characteristics of the tumor and
      tumor culture as compared to those of the endolymphatic sac. Findings support the
      hypothesis that aggressive papillary lesions of the temporal bone arise from the
      endolymphatic sac. Additionally, it is noted that the tumor culture maintains the
      characteristics of the original tumor and thus provides an exciting laboratory
      model for further study of this rare neoplasm.

PMID- 8572142
TI  - Teflon granuloma presenting as an enlarging, gadolinium enhancing, posterior
      fossa mass with progressive hearing loss following microvascular decompression.
AB  - Deleterious effects of Teflon strand placement during microvascular decompression
      (MVD) for hemifacial spasm are rare. In this report, a patient who had previously
      undergone suboccipital MVD for hemifacial spasm presented 3 years postoperatively
      with a progressive asymmetric sensorineural hearing loss and magnetic resonance
      imaging evidence of an enlarging ipsilateral gadolinium enhancing 1-cm
      cerebellopontine angle lesion. At surgery a granuloma was found displacing the
      structures of the internal auditory canal. Histologically, evidence of a Teflon
      fiber-induced giant cell granuloma was identified. This paper reviews the
      literature of Teflon-induced histopathology as it relates to posterior fossa MVD
      surgery, as well as its relation to this previously unreported complication.

PMID- 8572143
TI  - Short vestibulo-ocular reflex time-constant in complete unilateral vestibular
      lesions.
AB  - The time-constant of the vestibulo-ocular reflex (VORtc) in response to short
      accelerations was studied in 18 patients with complete unilateral vestibular
      lesions: 12 patients with incomplete lesions and 9 healthy controls. The marked
      group differences in VORtc, which was short in patients with complete lesions and
      long (i.e., > or = 10 s) in the controls and some patients with incomplete
      lesions, suggests the finding of a long VORtc in a patient with a unilateral
      vestibular lesion to indicate the presence of an incomplete lesion. Moreover, one
      analytic method (where the initial phase of decay is weighted) showed the VORtc
      to be longer following stimulation toward the healthy ear than following
      stimulation toward the lesioned ear, whereas other analytic methods showed no
      direction asymmetry in VORtc.

PMID- 8572144
TI  - Pediatric sensorineural hearing loss after temporal bone radiation.
AB  - In adults, sensorineural hearing loss (SNHL) resulting from megavoltage temporal
      bone radiation therapy (RT) is dose dependent. A review of the literature reveals
      only two cases of pediatric SNHL after RT without chemotherapy. This report
      presents four cases of late onset, asymmetric SNHL after RT in children treated
      for posterior fossa tumors. The children were treated with surgical resection of
      the tumor, followed by RT of 50 to 54 gray and no chemotherapy. These children,
      without evidence of tumor recurrence, developed severe SNHL 18 to 36 months after
      the completion of RT. Although no definite audiometric pattern was seen, most of
      the patients had a predominately high frequency SNHL in the poorer hearing ear,
      and fluctuant hearing in the better ear, without evidence of osteoradionecrosis
      or otitic infection. A review of the literature suggests that injury to the outer
      hair cells and cochlear neurons of the basal turn of the cochlea are possible
      sources for the hearing loss. Pretreatment audiologic evaluation as well as a
      minimum of 3 years of evaluations following RT would be prudent.

PMID- 8572145
TI  - Total artificial middle ear: preliminary report.
AB  - Reconstruction of a totally empty middle ear is difficult. This study reports
      results of 15 patients implanted with a total artificial middle ear developed on
      the principles of a total homologous middle ear and consisting of a canal wall
      prosthesis, a tympanic membrane/malleus prosthesis, and an incus/stapes
      prosthesis. Satisfactory results were noted in 12 of 15 patients at 1-year follow
      up, with air-bone gap closure within 30 dB; within 20 dB in seven of these
      twelve. However, at 3-year follow-up examination the total artificial middle ear
      was removed in seven cases due to obliteration and infection of the middle ear.
      These failures related to the extensive middle ear disease initially noted in
      these seven patients. These long-term results indicate the necessity of careful
      patient selection for reconstruction.

PMID- 8572146
TI  - Application of split-thickness skin grafts for acquired diseases of the external
      auditory canal.
AB  - Over the past 10 years a variety of acquired external auditory canal pathologies
      have been treated at the University of Virginia. Surgical intervention has been
      required in 16 patients (18 ears). The most common diagnosis in this group was
      canal stenosis. Split-thickness skin grafts have been used for epithelial
      coverage. Depending on the size and location of the canal defect, one of three
      graft types was used: island, segmental, or circumferential. Surgical techniques
      are discussed and illustrative cases presented. Long-term graft results have been
      excellent, with no patient requiring a second graft for coverage. In those
      patients with preoperative conductive losses, the average improvement in hearing
      threshold was 27 decibels.

PMID- 8572147
TI  - Reliability of examination data in the diagnosis of benign paroxysmal positional
      vertigo.
AB  - A practical clinical view of the reliability of the data obtained in the several
      steps of the examination procedure is discussed to obtain an objective basis for
      the selection of patients with provoked vertigo (benign paroxysmal positioning
      vertigo [BPPV]) in view of treatment of this type of vertigo by rehabilitation
      therapy. Clinical experience supports the concept that the diagnosis has to be
      based not only upon a typical history, but also upon the presence of a
      reproducible vertigo and paroxysmal positional nystagmus (ppn). Such a ppn can be
      reproduced not only as a "classic" nystagmus by the Dix-Hallpike maneuver, but
      also as a positional nystagmus and vertigo during electronystagmographic
      recording in the position tests and in the vestibular habituation training (VHT)
      test battery (a battery of 19 maneuvers applied for defining the adequate
      exercises in the rehabilitation treatment of BPPV). The ppn is not a constant
      reproductible sign in every patient, and in some, only one of these tests
      confirms the BPPV. This experience is confirmed by the analysis of the reviewed
      data in 95 patients, which showed that one third of the patients described their
      vertigo in a rather atypical way, whereas further testing revealed a BPPV. In
      this way any absolute reliability of history has to be denied. In fact, only the
      finding of a ppn is conclusive for confirming BPPV. However, as in former
      experiences, here too, the presence of such a ppn appeared not to be a constant
      datum, so that in some patients more than one examination was necessary to come
      to a reliable diagnosis. Patients in whom only vertigo could be reproduced, never
      confirmed by nystagmus, were excluded as an atypical ppv group.

PMID- 8572148
TI  - Tympanosclerosis in the tympanic membrane: influence on outcome of myringoplasty.
AB  - The effect of the presence of tympanosclerotic plaques in tympanic membrane on
      the outcome of a myringoplasty procedure was evaluated in this retrospective
      study. Long-term results of 714 myringoplasties were analyzed, and of these, 555
      were eligible for further study. Three groups were studied separately: ears
      without tympanosclerosis, ears with a plaque not exceeding one third of the
      tympanic membrane surface area, and ears with a plaque involving more than one
      third of the surface area extending to the border of the perforation. The latter
      group was subdivided into one in which during the operation the plaque was
      removed and one in which it was left in place. Take rate percentages as well as
      postoperative hearing results were calculated for each separate group of ears.
      Concerning graft take rate, it is concluded that the presence of tympanosclerosis
      in the tympanic membrane played no substantial part in the long-term outcome.
      With regard to postoperative hearing results, however, this study shows an
      average hearing gain of 6 dB when plaques exceeding one third of the tympanic
      membrane surface area were removed as part of the myringoplasty procedure.

PMID- 8572149
TI  - Validity of spontaneous perilymphatic fistula.
AB  - In response to recent articles questioning the validity of some perilymphatic
      fistula diagnoses, another small series is presented, reconfirming the enigmatic
      clinical appearance of perilymphatic fistula. Histologic evidence and
      experimental pathophysiology that explain the varied symptoms are reviewed. A
      pressed-fat fibrin-glue technique that seems to prevent recurrences is described,
      as well as a technique that may be helpful in confirming the presence of
      inapparent fistulas in surgery. Argument is advanced that this is a safe, minor
      surgical procedure helpful in alleviating vestibular and/or auditory symptoms in
      more than 70% of patients.

PMID- 8572150
TI  - Middle ear effects secondary to nasogastric intubation.
AB  - A study was conducted of the status of the middle ear in neurologically impaired
      patients requiring extended nasogastric tube (NGT) feeding. Ninety percent of the
      study patients with NGTs demonstrated abnormal middle ear function via immittance
      testing; whereas, 8.5% and 0% of the clinical and normal control samples,
      respectively, had abnormal findings. These results support the need to
      conscientiously observe the middle ear status of patients requiring long-term NGT
      feedings. A plan for monitoring middle ear function in these patients is
      suggested.

PMID- 8572151
TI  - A century ago in the American Journal of Otology.

PMID- 8572152
TI  - Correlates of breastfeeding frequency among nomadic pastoralists of Turkana,
      Kenya: a retrospective study.
AB  - Recent research has shown that significant variation in breast-feeding behavior
      exists among natural fertility populations, all of whom have been characterized
      as practicing "on-demand" breastfeeding. A number of recent prospective studies
      have contributed to a better understanding of breastfeeding structure and of its
      consequences for population differences in fertility. Currently, there is a
      growing interest in quantifying the complex environmental and biocultural
      interactions which influence that structure; in other words, in establishing an
      ecology of breastfeeding. In this paper, a carefully structured retrospective
      study of breastfeeding behavior among nomadic Turkana is used to identify
      environmental, biobehavioral, and socioeconomic factors associated with variation
      in breastfeeding frequency among Turkana women. In agreement with the results of
      a prospective study conducted as part of the same research, the age (growth) and
      physical development of nurslings show significant correlations with
      breastfeeding frequency. Maternal physical status, the depth of the maternal
      social network, and, to a lesser degree, rainfall patterns are also significant.
      All of these factors appear to influence breastfeeding through their effects on
      maternal participation in herding activities and related absences from camp.
      Finally, the study also presents new strategies for collecting and utilizing
      retrospective data, which are notoriously unreliable and difficult to classify
      according to operational definitions recently developed for prospective studies.
      Results of the present study suggest methods by which the quality and reliability
      of recall data may be enhanced.

PMID- 8572153
TI  - Genetic heterogeneity among the Hindus and their relationships with the other
      "Caucasoid" populations: new data on Punjab-Haryana and Rajasthan Indian states.
AB  - The genetic structure of Rajasthan Hindus and Punjab-Haryana Hindus and Sikhs has
      been studied for ABO, RH, APOC2, C6, C7, F13A, F13B, HP, ORM1, ACP1, ADA, AK1,
      ESD, GLO1, PGD, PGM1 subtyping, and PGP. This is the first genetic survey on
      Hindus of Rajasthan. Furthermore, many of these markers have never been studied
      on Hindus before (APOC2, C6, C7, F13A, F13B, ORM1, PGP). These data, together
      with those previously available for Hindus, have been utilized to analyze the
      within-Hindus genetic heterogeneity by RST statistic and correspondence analysis.
      The genetic relationships of Hindus to other Causcasoid populations were also
      investigated. In the first analysis, two eastern states (Orissa and Andhra
      Pradesh) were found to be quite separate from each other and clearly distinct
      from the northwestern and western states. Out of the markers which could not be
      utilized in this analysis, PGM1 subtyping turned out to discriminate between the
      Dravidian-speaking and the Indo-Aryan-speaking Hindus. The second analysis shows
      a clear-cut separation of Hindus from Europeans, with Near Eastern and Middle
      Eastern populations genetically in an intermediate position.

PMID- 8572154
TI  - Muscular and osseous anatomy of the primate anterior temporal fossa and the
      functions of the postorbital septum.
AB  - Many adaptive explanations for anthropoid origins incorporate hypotheses
      regarding the function of the postorbital septum. Two hypotheses are evaluated
      here: Cachel's ([1979b] Am. J. Phys. Anthropol. 50:1-18) hypothesis that the
      anthropoid postorbital septum evolved to augment muscle attachment area in the
      anterior temporal fossa and Cartmill's ([1980] in RL Ciochon and AB Chiarelli
      (eds.): Evolutionary Biology of the New World Monkeys and Continental Drift. New
      York: Plenum, pp. 243-274.) hypothesis that the septum evolved to insulate the
      foveate eye of haplorhines from movements in the temporal fossa during
      mastication. Dissections of the masticatory muscles of 55 species of primates,
      with emphasis on the anatomy of the anterior temporal fossa, reveal that in all
      anthropoids the temporal muscles take origin from the portion of the septum
      formed by the frontal bone. In some platyrrhines this muscle is anterior
      temporalis, and in others it is zygomatico-mandibularis. In tarsiers and most
      platyrrhines, muscle attachment to the zygomatic portion of the postorbital
      septum is very restricted (and of possibly varying homologies), whereas in
      catarrhines the zygomatico-mandibularis arises from the postorbital ridge on the
      zygomatic portion of the septum. This suggests that, contrary to Cachel's
      hypothesis, the earliest anthropoids did not have extensive areas of muscle
      attachment on the postorbital septum, a suggestion supported by the bony
      morphology of Catopithecus browni. Dissections also indicate that in all
      haplorhines the anteriormost temporal fibers curve around the postorbital septum
      between origin and insertion, implying that, were the septum not present, the
      anterior temporal muscles would disturb the orbital contents when contracting.
      This suggests that insulation may have been the septum's original function, even
      in the absence of a retinal fovea. In anthropoids, the rostral migration of the
      line of action of the anterior temporal muscles relative to the eye is attributed
      to their possession of extreme degrees of both orbital frontation and
      convergence; in tarsiers it is attributed to their possession of both massively
      hypertrophied eyes and moderately convergent and frontated orbits. It is argued
      that the postorbital septum is most likely to have evolved in a morphological
      context similar to that exhibited by omomyids.

PMID- 8572156
TI  - Functional morphology of indrid lumbar vertebrae.
AB  - Indrids are primarily vertical clingers and leapers but also engage to various
      extents in climbing, suspensory postures, bimanual movement, bipedal hopping, and
      quadrupedalism. It has been demonstrated that these behaviors are well reflected
      in the appendicular anatomy of these primates, while indrid vertebral anatomy has
      received relatively little attention. In this morphometric study, biomechanically
      relevant aspects of the lumbar vertebrae of Indri indri, Propithecus diadema, and
      Propithecus verreauxi were compared to those of Varecia variegata, a large-bodied
      predominantly pronograde and quadrupedal lemur. Results indicate that, compared
      to Varecia, the indrids have relatively shorter lumbar vertebral bodies, shorter
      lumbar regions, more dorsally projecting lumbar spinous processes, and more
      dorsally positioned lumbar transverse process tips. In addition, indrid lumbar
      spinous and transverse processes are oriented differently than those of Varecia.
      Overall, indrid lumbar vertebral morphology converges with that of hominoids,
      atelines, and possibly lorids, suggesting a lumbar adaptation to upright or
      "antipronograde" postures that require a reduction in spinal flexibility. The
      dorsally projecting spinous processes may be related to back muscle extensor
      power during leaping and/or the maintenance of upright postures. By contrast, the
      lumbar vertebrae of Varecia resemble those of primates and other mammals that
      have habitually pronograde postures and emphasize spinal flexibility in the
      sagittal plane during locomotion.

PMID- 8572155
TI  - Dental pathology in Pongo satyrus borneensis.
AB  - The Selenka orangutan collection obtained from 1892 to 1896 from wild-shot
      specimens in West Borneo, provides an excellent opportunity to examine dental
      pathology in free-ranging primates. Two hundred and twenty-three skulls from this
      collection were analyzed for dental conditions, including carious lesions, local
      infections (infra-alveolar and periapical osseous defects), horizontal bone loss,
      and premortem tooth loss. Specimens were sexed, divided into three broad age
      groups, and compared to ascertain sex-related or age-related differences in
      occurrence of dental pathology. None of the subadults displays any evidence of
      dental disease. One individual (2%) in the young adult group has a periapical
      osseous defect and evidence of horizontal bone loss, and another (2%) has two
      adjacent interproximal carious lesions. The old adults have a much higher
      prevalence of individuals afflicted with dental pathologies, including 6% carious
      lesions, 26% local infections, 23% horizontal bone loss, and 3% premortem tooth
      loss. The differences between the young and old adults in number of individuals
      afflicted with dental pathologies is statistically significant for local
      infections and horizontal bone loss. When compared by sex, the old adult group
      reveals that females have a higher occurrence of dental pathologies than males in
      all types of lesions recorded and these differences are statistically significant
      for local infections and horizontal bone loss. Considering the importance diet
      plays in the development of dental disease, it is suggested that ecological
      separation of the sexes, with the subsequent dietary differences, could be an
      important factor determining the higher prevalence of dental lesions observed in
      female orangutans. Additionally, the importance of local ecological factors,
      which may affect dietary patterns, are recognized as a potential source of
      variation in dental pathologies among different samples of orangutans.

PMID- 8572157
TI  - Determinants of postnatal weight in infant rhesus monkeys: implications for the
      study of interindividual differences in neonatal growth.
AB  - This paper provides an analysis of infant body weights obtained from a sample of
      38 rhesus monkey infants (Macaca mulatta) aged 29-165 days, i.e., animals still
      nutritionally dependent on their mothers. We examine the data on neonatal weights
      in relation to a number of factors, most notably, the sex of the infants, and the
      age and adiposity of their mothers. The infant body weights represent cross
      sectional rather than longitudinal data; because they were mostly free-ranging
      animals, the infants were weighted just once each. Nevertheless, the results of
      our analysis strongly suggest that early postnatal growth in free-ranging rhesus
      is dependent on both maternal fatness and age. They also suggest that, although
      male infants are generally heavier than like-aged female infants, they do not
      grow any faster during the early postnatal period. Here, we speculate that the
      associations between infant size and both maternal age and adiposity are the
      result of between-mother differences in lactational output.

PMID- 8572158
TI  - A simulation test of Smith's "Degrees of freedom" correction for comparative
      studies.
AB  - Computer simulation was used to test Smith's (1994) correction for phylogenetic
      nonindependence in comparative studies. Smith's method find effective N, which is
      computed using nested analysis of variance, and uses this value in place of
      observed N as the baseline degrees of freedom (df) for calculating statistical
      significance levels. If Smith's formula finds the correct df, distributions of
      computer-generated statistics from simulations with observed N nonindependent
      species should match theoretical distributions (from statistical tables) with the
      df based on effective N. The computer program developed to test Smith's method
      simulates character evolution down user-specified phylogenies. Parameters were
      systematically varied to discover their effects on Smith's method. In simulations
      in which the phylogeny and taxonomy were identical (tests of narrow-sense
      validity), Smith's method always gave conservative statistical results when the
      taxonomy had fewer than five levels. This conservative departure gave way to a
      liberal deviation in type I error rates in simulations using more than five
      taxonomic levels, except when species values were nearly independent. Reducing
      the number of taxonomic levels used in the analysis, and thereby eliminating
      available information regarding evolutionary relationships, also increased type I
      error rates (broad-sense validity), indicating that this may be inappropriate
      under conditions shown to have high type I error rates. However, the use of
      taxonomic categories over more accurate phylogenies did not create a liberal bias
      in all cases in the analysis performed here. The effect of correlated trait
      evolution was ambiguous but, relative to other parameters, negligible.

PMID- 8572159
TI  - Brief communication: a possible case of melorheostosis from antiquity.
AB  - An unusual case of discontinuous hard tissue hyperostosis is described in a 25-30
      year-old female dating between 4000 and 5500 BP from northern Chile. This
      specimen was one of 104 individuals examined from the Morro-1 site, which is
      known to represent the Chinchorro culture. The only other reported case from
      antiquity dates to 500 AD (Lester [1969] J. Bone Joint Surg. [Am.] 49:142-143). A
      review and comparison of this case to the medical literature supports a diagnosis
      of melorheostosis. Differential diagnosis is presented with the ruling out of
      nonspecific manifestations of osteomyelitis/periostitis as the most likely
      alternative diagnosis.

PMID- 8572160
TI  - Brief communication: skeletal evidence of operations on cadavers from Sens
      (Yonne, France) at the end of the XVth century.
AB  - Human remains giving direct evidence concerning the history of dissection
      practices are rare. Thirteen cranial fragments which bear evidence of having been
      purposely cut and sawn were discovered in a crypt during excavations undertaken
      in Sens (Yonne, France). Ceramics date these remains to the period from the end
      of the XIVth to the end of the XVIth centuries. Nine individuals are represented:
      one adolescent and eight adults of both sexes. The position of the cutmarks,
      which were produced by a long, sharp cutting tool, show that the scalp was
      completely removed from the skull. The sawing, which was done with a large
      toothed saw, was both clockwise and counterclockwise in direction. The sawn
      surfaces reveal a deliberate attempt not to damage the brain. This procedure is
      compared to that of modern autopsies. The remains from Sens are also compared
      with several other sawn cranial fragments recently discovered in France and
      England. Three hypotheses are discussed: embalmment, autopsy, and anatomical
      studies. Analysis of these remains and historical documentation suggest
      embalmment and/or autopsy as the probable purpose of the opening of the skull.

PMID- 8572161
TI  - Technical note: histological staining of secondary osteons.

PMID- 8572162
TI  - Regulation of protein synthesis and degradation in adult ventricular
      cardiomyocytes.
AB  - For studies on the regulation of myocardial protein metabolism, isolated adult
      cardiomyocytes were introduced as an experimental model about a decade ago. When
      used shortly after isolation, this model represents a tool for studying the
      properties of normal and diseased myocardium on the cellular level. The influence
      of various peptide hormones, neurotransmitters, and mechanical stimulation on
      protein synthesis and degradation in isolated cardiomyocytes has been studied. It
      has been demonstrated, for example, that alpha 1-adrenoceptor stimulation
      increases protein synthesis in newly isolated cardiomyocytes, independently of
      any mechanical effects. Other potential growth stimuli require appropriate
      conditions to induce cellular responsiveness. Neuropeptide Y, for example, does
      not stimulate cellular protein synthesis in newly isolated cells, whereas it does
      so in cells that have been cultured for a week in the presence of serum.
      Mechanical stretch also represents a growth stimulant. It seems that its signal
      transduction involves an autocrine loop. Thus different mechanisms, by which
      exogenous influences can modify cellular protein synthesis and degradation, have
      been identified on the cellular level, with the use of isolated adult
      cardiomyocytes.

PMID- 8572163
TI  - Unitary conductance of Na+ channel isoforms in cardiac and NB2a neuroblastoma
      cells.
AB  - Unitary conductances of native Na+ channel isoforms (gamma Na) have been
      determined under a variety of conditions, making comparisons of gamma Na
      difficult. To allow direct comparison, we measured gamma Na in cell-attached
      patches on NB2a neuroblastoma cells and rabbit ventricular myocytes under
      identical conditions [pipette solution (in mM): 280 Na+ and 2 Ca2+, pH 7.4; 10
      degrees C]. gamma Na of NB2a channels, 22.9 +/- 0.9 pS, was 21% greater than that
      of cardiac channels, 18.9 +/- 0.9 pS. In contrast, respective extrapolated
      reversal potentials, +62.4 +/- 4.6 and +57.9 +/- 5.1 mV, were not significantly
      different. Several kinetic differences between the channel types were also noted.
      Negative to -20 mV, mean open time (MOT) of the NB2a isoform was significantly
      less than that of cardiac channels, and, near threshold, latency to channel
      opening decayed more rapidly in NB2a. On the basis of analysis of MOT between -60
      and 0 mV, the rate constants at 0 mV for the open-to-closed (O-->C) and open-to
      inactivated (O-->I) transitions were 0.42 +/- 0.11 and 0.47 +/- 0.11 ms-1 in NB2a
      and 0.10 +/- 0.06 and 1.19 +/- 0.07 ms-1 in myocytes. The slope factors were 
      38.9 +/- 8.7 and +10.7 +/- 6.1 mV in NB2a and -27.3 +/- 7.1 and +23.7 +/- 4.9 mV
      in myocytes. Transition rate constants were significantly different in NB2a and
      cardiac cells, but voltage dependence was not.

PMID- 8572164
TI  - Additive effects of acidosis and parathyroid hormone on mouse osteoblastic and
      osteoclastic function.
AB  - Patients with end-stage renal disease are acidotic and often develop secondary
      hyperparathyroidism. Whether acidosis contributes to the bone disease observed in
      these patients is not clear. To determine whether acidosis and parathyroid
      hormone (PTH) have additive effects on net calcium efflux (JCa+) from bone and on
      bone cell function, we measured JCa+, osteoblastic collagen synthesis, and
      osteoclastic beta-glucuronidase release from neonatal mouse calvariae cultured in
      control (Ctl, pH approximately 7.4) or acidified (Met, pH approximately 7.1)
      medium with or without a submaximal concentration of PTH (10(-10) M) for 48 h.
      Compared with Ctl, from 24 to 48 h JCa+ was increased with Met and with PTH, and
      the combination of Met + PTH increased JCa+ further. Compared with Ctl, collagen
      synthesis was decreased with Met and with PTH and decreased further with Met +
      PTH. There was an inverse correlation between percent collagen synthesis and
      JCa+. Compared with Ctl, beta-glucuronidase release into the medium was increased
      with Met and with PTH and increased further with Met + PTH. There was a direct
      correlation between medium beta-glucuronidase activity and JCa+. Osteoclastic
      beta-glucuronidase activity correlated inversely with osteoblastic collagen
      synthesis. During cultures to 96 h, there continued to be greater JCa+ from
      calvariae incubated with Met + PTH than from those with either treatment alone.
      Thus acidosis and PTH independently stimulated JCa+ from bone, inhibited
      osteoblastic collagen synthesis, and stimulated osteoclastic beta-glucuronidase
      secretion, whereas the combination had a greater effect on each of these
      parameters than either treatment alone. These findings indicate that acidosis and
      PTH can have an additive effect on bone cell function and suggest that uremic
      osteodystrophy may result from a combination of a low pH and an elevated PTH.

PMID- 8572165
TI  - Regulation of endothelial cell nitric oxide synthase mRNA expression by shear
      stress.
AB  - Shear stress enhances expression of Ca(2+)-calmodulin-sensitive endothelial cell
      nitric oxide synthase (ecNOS) mRNA and protein in bovine aortic endothelial cells
      (BAEC). The present studies were performed to investigate mechanisms responsible
      for regulation of ecNOS mRNA expression by shear stress and to determine if this
      induction of ecNOS mRNA is accompanied by an enhanced nitric oxide (NO)
      production. Shear stresses of 15 dyn/cm2 for 3-24 h resulted in a two- to
      threefold increase of ecNOS mRNA content quantified by Northern analysis in BAEC.
      Shear stresses (1.2-15 dyn/cm2) for 3 h resulted in an induction of ecNOS mRNA in
      a dose-dependent manner. In human aortic endothelial cells, shear stresses of 15
      dyn/cm2 for 3 h also resulted in ecNOS mRNA induction. In BAEC, this induction in
      ecNOS mRNA was prevented by coincubation with actinomycin D (10 micrograms/ml).
      The K+ channel antagonist tetraethylammonium chloride (3 mM) prevented increase
      in ecNOS mRNA in response to shear stress. The ecNOS promotor contains putative
      binding domains for AP-1 complexes, potentially responsive to activation of
      protein kinase C (PKC). However, selective PKC inhibitor calphostin C (100 nM)
      did not inhibit ecNOS induction by shear stress. Finally, production of nitrogen
      oxides under both basal conditions and in response to the calcium ionophore A
      23187 (1 microM) by BAEC exposed to shear stress was increased approximately
      twofold compared with cells not exposed to shear stress. These data suggest that
      ecNOS mRNA expression is regulated by K+ channel opening, but not by activation
      of PKC, and that shear not only enhances ecNOS mRNA expression but increases
      capacity of endothelial cells to release NO.

PMID- 8572166
TI  - Activation of adenylyl cyclase downregulates sodium/calcium exchanger of arterial
      myocytes.
AB  - Chronic elevation of adenosine 3',5'-cyclic monophosphate (cAMP) is known to
      inhibit the proliferation of cultured vascular smooth muscle cells. The present
      findings show that the activation of adenylyl cyclase with forskolin decreased
      Na+/Ca2+ exchanger (NCX) mRNA and activity. Fetal bovine serum restored NCX
      transcript and activity. The changes in NCX transcript preceded the changes in
      NCX activity. Incubation of low-passage immortalized myocytes with forskolin plus
      3-isobutyl-1-methylxanthine (IBMX), which inhibits cAMP phosphodiesterase,
      decreased NCX mRNA by 60% in 6 h and 80% in 24 h. After a 6-h lag, forskolin plus
      IBMX decreased NCX activity almost linearly to 20% of control at 40 h. 1,9
      Dideoxyforskolin, which does not activate adenylyl cyclase, had no effect on NCX
      mRNA or activity. Forskolin plus IBMX decreased the c-Myc transcript, an
      immediate-early gene whose expression correlates with cell proliferation, but had
      no effect on plasma membrane Ca(2+)-ATPase transcripts. Removal of forskolin plus
      IBMX and addition of fetal bovine serum increased NCX and c-Myc transcripts seven
      to eightfold in 6 h and restored NCX activity in 24 h. Inhibition of protein or
      RNA synthesis by cycloheximide or actinomycin D, respectively, prevented the
      increase in NCX mRNA. In contrast to blocking NCX induction, cycloheximide
      potentiated c-Myc induction by serum. Transcription factors that regulate myocyte
      growth may mediate the opposing influences of serum and forskolin on NCX mRNA and
      activity.

PMID- 8572167
TI  - Lysophosphatidic acid, serum, and hyposmolarity activate Cl- currents in corneal
      keratocytes.
AB  - The influence of serum, lysophosphatidic acid (LPA), and hyposmotic stress on the
      ion channel activity of normal and cryo-injured rabbit corneal keratocytes was
      investigated. Whole cell currents were examined using the amphotericin perforated
      patch technique. In cells from wounded corneas, fetal bovine serum activated
      large, holding voltage-insensitive, fast-activating, 4,4'-diisothiocyanostilbene
      2,2'-disulfonic acid (DIDS)-, flufenamic acid-, and 5-nitro-2-(3
      phenylpropylamino)benzoic acid (NPPB)-blockable outward currents showing
      inactivation at depolarized voltages. LPA activated identical currents, also only
      in cells from wounded corneas. Blocker and reversal potential experiments
      characterized the current as a Cl- currents (Icl). Lysophosphatidylcholine (10
      microM) failed to activate the current. An identical current was activated by
      hyposmotic stimulation in cells from control and wounded corneas. Hyposmotic
      stimulation also activated Icl in cells from wounded corneas that were
      unresponsive to LPA. We conclude that serum, LPA, and hypotonic stress activate
      Icl in keratocytes from wounded corneas. We also conclude that LPA is a serum
      factor that can activate Icl and that hyposmotic activation may work through a
      signaling pathway separate from that of LPA.

PMID- 8572168
TI  - Tachykinins activate nonselective cation currents in canine colonic myocytes.
AB  - The mechanism of tachykinin-induced excitation was studied in isolated colonic
      muscle cells and intact muscle strips. In whole cell voltage-clamp studies
      performed at 33 degrees C, neurokinin A (NKA) and substance P (SP) reduced L-type
      Ca2+ current. NKA and SP activated a cationic current that reversed near 0 mV.
      This current (INKA or ISP, respectively) had properties similar to the
      acetylcholine (ACh)-activated nonselective cation conductance (IACh), activated
      by muscarinic stimulation in other gastrointestinal smooth muscle cells. INKA and
      ISP were decreased when external Na+ was reduced. In contrast to IACh, INKA and
      ISP were not facilitated by increases in internal Ca2+, but little or no current
      was activated by these peptides when extracellular Ca2+ was low. INKA (10(-7) M)
      and ISP (10(-5) M) were blocked by Cd2+ (5 x 10(-4) M), quinine (10(-3) M), and
      the tachykinin-receptor antagonist [D-Pro2,D-Trp7,9]SP (10(-5) M). Current clamp
      recordings and intracellular recordings of intact tissues showed that NKA and SP
      depolarized the cell membrane, which is consistent with the activation of a
      nonselective cation conductance. These data suggest that a primary mechanism of
      the tachykinins is to activate a nonselective cation conductance that leads to
      depolarization. The increase in Ca2+ entry due to tachykinin stimulation appears
      to be secondary to the activation of the nonselective cation conductance.

PMID- 8572169
TI  - Memory of arterial receptor activation involves reduced [Ca2+]i and
      desensitization of cross bridges to [Ca2+]i.
AB  - Rabbit femoral arteries retain a memory of previous maximum receptor activation
      for up to 3-4 h after complete cessation of the stimulus, as reflected by a
      reduction in the steady-state contraction produced by a subsequent exposure to
      KCl. The present study examined the hypothesis that this modulatory effect
      involves alterations in postreceptor signal transduction. To quantify the degree
      of cellular downregulation induced by an episode of alpha 1-adrenoceptor
      stimulation, tissues were pretreated for 30 min with 10(-5) M phenylephrine (PE),
      washed for 10 min to cause complete relaxation, and activated with increasing
      concentrations of KCl. Pretreatment of tissues with PE resulted in a large
      reduction compared with control tissues in the ability of 20-60 mM KCl to
      increase stress and myosin light-chain phosphorylation. However, only at low (20
      and 26 mM), not high (> 26 mM), KCl concentrations did PE pretreatment reduce the
      ability of KCl to increase intracellular free Ca2+ concentration ([Ca2+]i). These
      data support the hypothesis that memory of receptor activation involves
      reductions in both Ca2+ mobilization and the sensitivity of contractile proteins
      to [Ca2+]i.

PMID- 8572170
TI  - Role of C/EBP proteins in hepatic and vascular smooth muscle transcription of
      human NHE1 gene.
AB  - We have recently shown that regulatory element D (nucleotides -239 to -215) of
      the 0.25-kb promoter of the human growth factor-activatable Na+/H+ exchanger
      (NHE1) is important for gene transcription in cells of hepatic origin (Hep G2)
      and vascular smooth muscle origin (VSM A7r5). This element contains a sequence
      (nucleotides -230 to -222) with complete homology to the C/EBP binding site. We
      now demonstrate that nucleotide substitution mutations disrupting this C/EBP site
      suppressed transcription in Hep G2 cells, VSM A7r5 cells, and Sprague-Dawley VSM
      cells in primary culture. These mutations abolished the binding of rat liver
      nuclear activities as well as transcription factors C/EBP alpha, C/EBP beta, and
      C/EBP delta expressed in COS-1 cell lysates to element D. Anti-C/EBP antibodies
      supershifted DNA-protein complexes formed between hepatic nuclear activities or
      C/EBP proteins expressed in COS-1 cell lysates and regulatory element D. Finally,
      cotransfection experiments of NHE1 0.25-kb promoter-chloramphenicol
      acetyltransferase (CAT) construct and C/EBP expression vectors showed that C/EBP
      alpha and C/EBP delta are transactivators of the NHE1 proximal promoter in Hep G2
      and VSM A7r5 cells. These results indicate that members of the C/EBP family of
      transcription factors are involved in the regulation of hepatic and vascular
      smooth muscle transcription of the human NHE1 gene.

PMID- 8572171
TI  - Differential expression of Na(+)-K(+)-ATPase, ankyrin, fodrin, and E-cadherin
      along the kidney nephron.
AB  - Ionic homeostasis in vertebrates is maintained by epithelial cells that line
      kidney nephrons. Transport of ions and solutes is coupled to Na+ reabsorption
      from the ultrafiltrate and requires specific subcellular distribution and
      activity of Na(+)-K(+)-ATPase along the nephron. Studies using cell culture
      models of renal epithelia indicate that the subcellular distribution of Na(+)
      K(+)-ATPase is regulated by interactions with the submembrane cytoskeleton and E
      cadherin-mediated adherens junctions. We have now examined the relevance of these
      in vitro observations to the subcellular organization of these proteins in
      different nephron segments of the adult mouse kidney using immunofluorescence
      microscopy. Our results demonstrate that segmental and subcellular distributions
      of Na(+)-K(+)-ATPase and the membrane-cytoskeletal proteins, ankyrin and fodrin,
      vary in parallel along the nephron and do not parallel variations in expression
      of the tight junction protein ZO-1 or E-cadherin. These data indicate that a
      mechanism for restricting Na(+)-K(+)-ATPase subcellular distributions through
      interactions with the membrane cytoskeleton is likely to be relevant in vivo.

PMID- 8572172
TI  - Differential expression of cell-cell and cell-substratum adhesion proteins along
      the kidney nephron.
AB  - Structural and functional differences among epithelial cells of kidney nephrons
      may be regulated by variations in cell-to-cell (cell-cell) and cell-to-substratum
      (cell-substratum) junctions. Using immunofluorescence microscopy, we demonstrate
      that the cadherin-associated proteins alpha- and beta-catenin are localized to
      basolateral membranes of cells in all nephron segments, whereas plakoglobin, a
      protein associated with both classical and desmosomal cadherins, is localized to
      noninterdigitated lateral membranes in the distal half of the nephron where it
      colocalizes with desmoplakin and cytokeratin K8. Plakoglobin is also present in
      capillary endothelial cells where staining for the other catenins and desmosomal
      proteins is not observed. Immunofluorescence for laminin A and alpha 6-integrin,
      proteins that mediate cell-substratum contacts, reveal no correlations with the
      other staining patterns observed. These data indicate that plakoglobin and beta
      catenin subserve distinct functions in cell-cell adhesion and suggest that E
      cadherin-mediated contacts generate a basal level of cell-cell adhesion, whereas
      desmosomal junctions provide additional strength to cell-cell contacts in the
      distal nephron.

PMID- 8572173
TI  - Immunolocalization of aquaporin CHIP in the guinea pig inner ear.
AB  - Aquaporin CHIP (AQP-CHIP) is a water channel protein previously identified in red
      blood cells and water transporting epithelia. The inner ear is an organ of
      hearing and balance whose normal function depends critically on maintenance of
      fluid homeostasis. In this study, AQP-CHIP, or a close homologue, was found in
      specific cells of the inner ear, as assessed by immunocytochemistry with the use
      of affinity-purified polyclonal antibodies against AQP-CHIP.AQP-CHIP was
      predominantly found in fibrocytes in close association with bone, including most
      of the cells lining the bony labyrinth and in fibrocytes lining the endolymphatic
      duct and sac. AQP-CHIP-positive cells not directly apposing bone include cells
      under the basilar membrane, some type III fibrocytes of the spiral ligament,
      fibrocytes of the spiral limbus, and the trabecular perilymphatic tissue
      extending from the membranous to the bony labyrinth. AQP-CHIP was also found in
      the periosteum of the middle ear and cranial bones, as well as in chondrocytes of
      the oval window and stapes. The distribution of AQP-CHIP in the inner ear
      suggests that AQP-CHIP may have special significance for maintenance of bone and
      the basilar membrane, and for function of the spiral ligament.

PMID- 8572174
TI  - Stimulation of Cl- secretion by extracellular ATP does not depend on increased
      cytosolic Ca2+ in HT-29.cl16E.
AB  - Extracellular ATP and elevated cytosolic Ca2+ concentration ([Ca2+]i) are major
      secretagogues for Cl- in the goblet cell-like clone cl.16E derived from colonic
      HT-29 cells. The involvement of [Ca2+]i as a messenger for the purinergically
      stimulated Cl- secretion was investigated using whole cell patch-clamp and Ussing
      chamber techniques, as well as [Ca2+]i measurements using fura 2-loaded cells.
      Under voltage-clamp conditions, the whole cell current at +50 mV was 3 +/- 1
      pA/pF under unstimulated conditions. Stimulation of purinergic receptors with 200
      microM extracellular ATP increased the current at +50 mV to 41 +/- 10 pA/pF, with
      a half-maximal effective dose (ED50) of approximately 3 microM. The current was
      transient, usually lasting 1-2 min, and the current-voltage relationship was
      approximately linear between -70 and +50 mV. Evidence that the ATP-stimulated
      current was carried by Cl- included 1) the reversal potential of the current
      closely followed the Cl- equilibrium potential, and 2) the stimulated current was
      absent when Cl- was removed from both bath and pipette solutions. Exposure to ATP
      also increased [Ca2+]i, with an ED50 of approximately 1 microM and maximal
      changes (at 200 microM) from baseline (71 +/- 3 nM) to 459 +/- 50 nM. The ATP
      dependent Cl- conductance increase was not diminished when [Ca2+]i was clamped at
      100 nM using a Ca(2+)-1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
      or Ca(2+)-ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid
      buffering system. However, the ATP effect did require some basal level of Ca2+
      because clamping [Ca2+]i at < 10 nM abolished activation of the Cl- conductance.
      The presence of the protein kinase A inhibitor H-89 or the protein kinase C
      inhibitor staurosprine did not change the ATP-activated Cl-conductance. These
      data demonstrate that the ATP-stimulated increase in Cl- current does not require
      an increase in [Ca2+]i, suggesting the involvement of either another signaling
      pathway or direct activation of Cl- channels by purinergic receptors.

PMID- 8572175
TI  - Calcium currents in postinfarction rat cardiac myocytes.
AB  - Myocytes isolated from rat hearts that have suffered 35% myocardial infarction
      (MI) 3 wk prior have lower peak cytosolic Ca2+ concentration ([Ca2+]i) during
      contraction compared with Sham myocytes, a difference that is amplified by
      isoproterenol or high extracellular Ca2+ concentration ([Ca2+]o). To evaluate
      whether reduced [Ca2+]i in MI myocytes is due to decreased Ca2+ entry, we
      measured [3H]PN-200-110 [dihydropyridine (DHP)] binding and whole cell Ca2+
      current (ICa). DHP binding decreased in both sarcolemmal vesicles and intact
      myocytes from hearts 3 wk after MI. In contrast, ICa was not different between
      Sham and MI myocytes incubated at 1.8 mM [Ca2+]o. At 5.0 mM [Ca2+]o, ICa
      increased similarly in Sham and MI myocytes. Steady-state voltage dependence of
      activation and inactivation were similar between Sham and MI myocytes, as were
      the fast- and slow-inactivation time constants. Isoproterenol (1 microM)
      significantly increased ICa in Sham but not in MI myocytes. Forskolin (10 microM)
      dibutyryl adenosine 3',5'-cyclic monophosphate (5 mM) significantly increased ICa
      in MI myocytes; the magnitude of ICa increase was similar to that observed in
      Sham myocytes. We conclude that 1) decreased systolic [Ca2+]i in MI myocytes was
      not due to reduced Ca2+ entry via L-type Ca2+ channels; 2) discrepancy between
      DHP binding (decrease) and ICa (no change) results may be explained by higher
      channel availability and/or increased long-opening modes (mode 2) in MI myocytes;
      3) reduction in isoproterenol-induced [Ca2+]i increase in MI myocytes was partly
      due to decreased ICa, resulting in less Ca2+ release from sarcoplasmic reticulum;
      4) the adenylate cyclase-protein kinase A signal-transduction pathway functioned
      normally in MI myocytes; and 5) decreased beta-adrenergic responsiveness in MI
      myocytes was likely due to altered coupling by G proteins.

PMID- 8572176
TI  - Gastrin stimulates expression of protooncogene c-myc through a process involving
      polyamines in IEC-6 cells.
AB  - The current study tested the hypothesis that the protooncogene c-myc is involved
      in the mechanism by which gastrin modulates mucosal cell proliferation. Studies
      were conducted in the IEC-6 cell line, derived from rat small intestinal crypt
      cells. Administration of gastrin resulted in the rapid appearance of c-myc mRNA
      in IEC-6 cells. The increased expression of c-myc began 1 h and peaked 4 h after
      exposure to gastrin. Maximum increase in c-myc mRNA levels was 7.5-fold the
      normal value. When cellular protein synthesis was inhibited by addition of
      cycloheximide, gastrin superinduced c-myc mRNA levels. Gastrin also significantly
      increased the mRNA levels for ornithine decarboxylase (ODC), the rate-limiting
      enzyme for polyamine biosynthesis, enzyme activity, and intracellular polyamines
      in IEC-6 cells. Treatment with alpha-difluoromethylornithine (DFMO), a specific
      inhibitor of ODC, not only completely depleted intracellular polyamines but also
      significantly prevented the increased expression of c-myc in cells exposed to
      gastrin. These results show that 1) gastrin stimulates both polyamine
      biosynthesis and the expression of the c-myc protooncogene, and 2) depletion of
      intracellular polyamines by DFMO significantly prevented the increased expression
      of c-myc by gastrin.

PMID- 8572177
TI  - Hyperglycemia alters cytoplasmic Ca2+ responses to capacitative Ca2+ influx in
      rat aortic smooth muscle cells.
AB  - Concentrations of free cytoplasmic Ca2+ in rat aortic smooth muscle (RASM) cells
      were monitored using the ratiometric Ca2+ indicator fura 2-acetoxymethyl ester
      (AM). In RASM cells cultured in 5 mM Glc, incubation with angiotensin II, ATP, or
      thapsigargin [a selective inhibitor of the sarcoplasmic reticulum (SR) Ca(2+)
      ATPase] depleted SR Ca2+ stores and initiated a capacitative Ca2+ influx through
      the plasma membrane. This influx was resistant to verapamil, a selective
      inhibitor of L-type voltage-gated Ca2+ channels, but was sensitive to SKF-96365,
      an inhibitor of the receptor-operated Ca2+ entry pathway. RASM cells cultured in
      25 mM Glc exhibited a significant decrease in cytoplasmic Ca2+ responses to
      agonist-induced Ca2+ release from SR stores and to subsequent capacitative Ca2+
      entry. In addition, the cytoplasmic response to thapsigargin-induced release of
      Ca2+ from the SR in hyperglycemic cells peaked more sharply than in control cells
      and returned to baseline more rapidly. The effects of hyperglycemia were not
      overcome by myo-inositol supplementation.

PMID- 8572178
TI  - Arachidonic acid stimulates protein tyrosine phosphorylation in vascular cells.
AB  - Arachidonic acid and its metabolites are important cellular mediators. In this
      study, we report a novel role for arachidonic acid in vascular cell signaling. We
      tested the effects of exogenous arachidonic acid on protein tyrosine
      phosphorylation in cultured vascular endothelial and smooth muscle cells.
      Arachidonic acid stimulated the phosphorylation of tyrosine-containing proteins
      of approximately 58, 93, and 120 kDa in the three cell types studied. This
      response was dose dependent, with a maximum effect observed with 40 microM
      arachidonic acid. Phosphorylation was rapid and transient, reaching a peak 0.5
      min after the addition of arachidonic acid and returning to baseline by 8 min. A
      common set of protein substrates was phosphorylated in smooth muscle cells
      treated with the Ca(2+)-mobilizing agonist endothelin, concomitant with an
      increase in endogenous unesterified arachidonic acid. To determine whether the
      protein tyrosine phosphorylation was due to arachidonic acid or to a metabolite,
      we used inhibitors of cyclooxygenase, lipoxygenase, and epoxygenase pathways.
      Ibuprofen, nordihydroguaiaretic acid, eicosatriynoic and eicosatetraynoic acids,
      and 8-methoxypsoralen failed to inhibit the arachidonic acid-mediated response.
      We also found increased protein tyrosine phosphorylation after treatment with
      oleic, linolenic and gamma-linoleic acid. These results suggest a mechanism of
      protein tyrosine phosphorylation that is directly stimulated by unmetabolized
      unsaturated fatty acids.

PMID- 8572179
TI  - Distribution and diversity of Na-K-Cl cotransport proteins: a study with
      monoclonal antibodies.
AB  - The Na-K-Cl cotransporter (NKCC) is present in most animal cells where it
      functions in cell volume homeostasis and epithelial salt transport. We developed
      six monoclonal antibodies (designated T4, T8, T9, T10, T12, and T14) against a
      fusion protein fragment encompassing the carboxy-terminal 310 amino acids of the
      human colonic NKCC. These T antibodies selectively recognized putative NKCC
      proteins in a diverse variety of animal tissues. Western blot analysis of
      membranes isolated from 23 types of cells identified single bands of
      immunoreactive protein ranging in mass from 146 to 205 kDa. The amount of
      immunoreactive protein detected in these cells correlated with loop diuretic
      binding site density. Proteins identified previously as Na-K-Cl cotransporters by
      loop diuretic photoaffinity labeling were mutually recognized by multiple T
      antibodies. Most of the T antibodies effectively immunoprecipitated the denatured
      form of the NKCC protein. Immunocytochemical studies on the rabbit parotid gland
      demonstrated that NKCC is restricted to the basolateral margin of the acinar
      cells and absent from the ducts, in accord with the central role of Na-K-Cl
      cotransport in chloride secretion. In the rabbit kidney, NKCC was localized to
      the apical membrane of thick ascending limb cells, consistent with its role in
      chloride reabsorption.

PMID- 8572180
TI  - Astroglial cell-induced expression of Na-K-Cl cotransporter in brain
      microvascular endothelial cells.
AB  - Endothelial cells of the blood-brain barrier (BBB) are characterized by extensive
      tight junctions and asymmetric distribution of specific enzymes and transport
      systems. Maintenance of the BBB endothelial phenotype depends on astrocyte
      endothelial interactions. We showed previously that cultured cerebral
      microvascular endothelial cells (CMEC) exhibit robust Na-K-Cl cotransport
      activity. In the present study, we evaluated the expression of Na-K-Cl
      cotransport protein in CMEC by quantitative Western blot analysis and found that
      a protein of approximately 170 kDa was recognized by a monoclonal antibody
      against the cotransporter. Exposure of CMEC to astroglial cells or their
      conditioned media increased the expression of the CMEC cotransport protein by
      approximately 55%. Using a monoclonal antibody against the alpha-subunit of
      chicken Na-K-ATPase, we found that these treatments also increased expression of
      Na-K-ATPase protein by a similar amount. By comparing bumetanide-sensitive K
      influx and [3H]bumetanide binding apical vs. basolateral surfaces of CMEC, we
      found both cotransporter activity and [3H]bumetanide binding to be approximately
      90% apical and 10% basolateral. Coculture of the CMEC with astroglial cells
      increased cotransport activity and [3H]bumetanide binding at both surfaces, with
      the asymmetric distribution maintained. These results indicate that the
      cotransporter is regulated by astroglial cells and that an apically distributed
      CMEC cotransporter may function in tandem with the basolateral Na-K-ATPase to
      mediate vectorial transport of Na and Cl across the BBB.

PMID- 8572181
TI  - Endothelial Na-K-Cl cotransport regulation by tonicity and hormones:
      phosphorylation of cotransport protein.
AB  - The Na-K-Cl cotransport system of vascular endothelial cells plays a central role
      in maintenance and regulation of intracellular volume. Activity of the
      cotransporter is modulated both by hormones and by extracellular tonicity.
      Vasopressin and other hormones that stimulate the endothelial cotransporter act
      via a Ca- and calmodulin-dependent pathway. Little is known, however, about the
      mechanisms that mediate cell shrinkage-induced stimulation of cotransport
      activity. In the present study, we evaluated the Ca dependence of cell shrinkage
      stimulated Na-K-Cl cotransport activity and cell volume recovery of cultured
      bovine aortic endothelial cells and also the effects of protein kinase and
      phosphatase inhibitors on these processes. In addition, to investigate the
      possibility that hormones and/or hypertonicity regulate endothelial Na-K-Cl
      cotransport via direct phosphorylation of the cotransporter protein, we employed
      a monoclonal antibody to the human colonic T84 epithelial cell Na-K-Cl
      cotransport protein (T4 antibody) for Western blot analysis and
      immunoprecipitation of phosphoprotein. Our studies revealed that both cell
      shrinkage-stimulated net K uptake and recovery of intracellular volume were Ca
      dependent. We also found that hypertonicity-induced stimulation of cotransport
      activity was blocked by several inhibitors of Ca- and calmodulin-dependent
      protein kinases. Furthermore, inhibitors of myosin light chain kinase blocked
      cell shrinkage-stimulated cotransport and recovery of intracellular volume, while
      having no effect on vasopressin-stimulated cotransport. Western blot analysis of
      bovine aortic and cerebral microvascular endothelial cell membrane preparations
      revealed a 170-kDa protein recognized by the T4 antibody. In addition, we found
      that hypertonicity induced a marked increase in phosphorylation of the
      endothelial cotransport protein, as did vasopressin, bradykinin, okadaic acid,
      and calyculin A. Our findings indicate that modulation of endothelial cell Na-K
      Cl cotransport activity by hypertonicity and by stimulatory hormones occurs via
      pathways involving Ca- and calmodulin-dependent protein kinases and direct
      phosphorylation of the cotransport protein.

PMID- 8572182
TI  - Volume-sensitive myosin phosphorylation in vascular endothelial cells:
      correlation with Na-K-2Cl cotransport.
AB  - To identify protein kinases that are regulated by cell volume, we examined
      protein phosphorylation in hypertonically shrunken aortic endothelial cells.
      Shrinkage reversibly increased, and swelling decreased, phosphorylation of a 19
      kDa cytoskeletal protein identified as myosin light chain (MLC) by immune
      precipitation and immunoblotting. Shrinkage also increased MLC phosphorylation in
      human umbilical vein endothelial cells, rat aortic smooth muscle cells, and human
      dermal fibroblasts. Phosphorylation was blocked by ML-7, an inhibitor of MLC
      kinase (MLCK). Neither inhibition of protein kinase C nor inhibition of myosin
      phosphatase (with calyculin) altered MLC phosphorylation. Peptide mapping of MLC
      indicated phosphorylation by MLCK. Na-K-2Cl cotransport activation paralleled MLC
      phosphorylation in hypertonic medium. Na-K-2Cl was stimulated by low
      concentrations of ML-7 with no further stimulation by hypertonic shrinkage and
      was inhibited by higher concentrations, paralleling inhibition of MLC
      phosphorylation. Shrinkage-induced phosphorylation of the cotransporter was not
      blocked by ML-7. We conclude that cell volume regulates MLC phosphorylation by
      MLCK. MLCK influences Na-K-2Cl cotransport but independently of cotransporter
      phosphorylation. These data suggest an important link between cell volume, volume
      regulatory transporters, and the contractile state of the cytoskeleton.

PMID- 8572183
TI  - Regulation of the cross-bridge transition from a weakly to strongly bound state
      in skinned rabbit muscle fibers.
AB  - The regulation of cross-bridge transition from weakly attached to force-bearing
      states was studied at 10 degrees C in skinned muscle fibers by measuring the rate
      of force development after a quick release-restretch cycle (ktr), the rate of
      force decline (kPi) after photogeneration of Pi from caged Pi, and stiffness in
      the presence and absence of an inhibitor of strong cross-bridge formation, 2,3
      butanedione monoxime (BDM). Both BDM and Pi suppressed force more than stiffness.
      However, reduction of Ca2+ suppressed force and stiffness in a parallel fashion.
      Both ktr and kPi were reversibly reduced (by 30-35%) in 3 mM BDM, but both were
      increased by increasing Pi concentration. Reduction of Ca2+ concentration to
      match the force seen in 3 mM BDM had no effect on kPi but decreased ktr by 85%.
      These results are inconsistent with cross-bridge models undergoing the transition
      from a weakly bound to a force-generating state in a single step but are
      consistent with a model having two steps, one of which is controlled by pCa.

PMID- 8572184
TI  - Differential Ca2+ responses of adrenergic and noradrenergic chromaffin cells to
      various secretagogues.
AB  - The effects of several physiological agonists on the cytosolic Ca2+ concentration
      ([Ca2+]i) of immunnocytochemically identified single adrenergic and noradrenergic
      bovine chromaffin cells were compared. No differences were observed in the
      responses to stimulation by high-K+ solutions with or without BAY K 8644,
      suggesting that the density and properties of voltage-dependent Ca2+ channels
      were similar in both cell types. The increase of [Ca2+]i induced by acetylcholine
      was greater in adrenergic cells, and this was due to differences in the response
      mediated through nicotinic receptors. The responses to bradykinin and to ATP were
      slightly greater in noradrenergic cells. Only a small fraction of the cells (18
      28%) was responsive to ATP. The responses to angiotensin II and to histamine were
      much greater in adrenergic than in noradrenergic cells. Histamine was almost a
      selective stimulator of adrenergic cells. These differences suggest differential
      distribution of functional membrane receptors in both cell types and may be
      relevant to understanding the differential contribution of epinephrine- and
      norepinephrine-secreting cells during stressful conflicts in physiological or
      pathophysiological situations.

PMID- 8572185
TI  - Evidence for voltage-sensitive, calcium-conducting channels in airway epithelial
      cells.
AB  - In airways epithelial cultures, mechanical stimulation induces intracellular Ca2+
      concentration ([Ca2+]i) changes by causing Ca2+ entry and intracellular Ca2+
      release. Mechanically induced Ca2+ fluxes across the plasma membrane are blocked
      by Ni2+ (Boitano, S., M. J. Sanderson, and E. R. Dirksen. J. Cell. Sci. 107: 3037
      3044, 1994). In this report we use fluorescence imaging microscopy with fura 2
      and intracellular recording of the transmembrane potential to further
      characterize Ca2+ flux in the plasma membrane of these cells. Mechanically
      induced Ca2+ influx is blocked by nifedipine. Addition of the dihydropyridine
      agonist BAY K8644 (2 microM) leads to a delayed increase of [Ca2+]i that is
      dependent on extracellular Ca2+. Switching to high extracellular K+ concentration
      ([K+]o) causes depolarization of the plasma membrane and a transient increase in
      [Ca2+]i. The number of cells that respond to high [K+]o is significantly
      decreased by Ni2+ (1 mM) or nifedipine (10 microM). Mechanical stimulation causes
      a rapid depolarization of the stimulated cell that can be suppressed by the K+
      ionophore valinomycin. Valinomycin treatment also blocks mechanically induced
      Ca2+ dux. These results suggest that voltage-sensitive Ca(2+)-conducting channels
      exist in airway epithelial cells, and these channels contribute to the [Ca2+]i
      changes observed after mechanical stimulation or depolarization of the plasma
      membrane.

PMID- 8572186
TI  - Quantitative confocal imaging along the crypt-to-surface axis of colonic crypts.
AB  - Quantitative confocal microscopy methods are used to measure events along the
      crypt-to-surface axis in living mouse colonic mucosa. Experiments visualize
      carboxyseminaphthorhodofluor-1 (SNARF-1; a pH-sensitive fluorescent dye) in the
      extracellular fluid to measure extracellular pH within an intact epithelium.
      Lucifer yellow (LY; a pH-insensitive dye) is used to control for fidelity of the
      optical path. Light scatter from colonic tissue caused SNARF-1 or LY fluorescence
      to decrease 3% per micrometer focal distance into tissue at both 640- and 580-nm
      emission wavelengths. However, dual emission ratios of LY fluorescence were
      constant as a function of focal distance into tissue or in the presence of short
      chain fatty acids (SCFA). SCFA, known to cause changes in extracellular pH, cause
      maximal changes in crypt luminal pH at 10 microns from the crypt base. Maximal
      changes of pH in lamina propria occur higher along the crypt-to-surface axis than
      maximal changes in luminal pH. Lateral intercellular spaces between colonocytes
      are a separate microdomain in which pH is constant in absence vs. presence of
      SCFA and along the base-to-apex axis of colonocytes.

PMID- 8572187
TI  - Epitope tagging permits cell surface detection of functional CFTR.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a
      phosphorylation-activated Cl channel responsible for adenosine 3',5'-cyclic
      monophosphate (cAMP)-induced Cl secretion across the apical membranes of
      epithelial cells. To optimize its detection for membrane localization studies, we
      tagged CFTR with epitope sequences at the carboxy terminus or in the fourth
      external loop. When epitopes were added to the fourth external loop, the N-linked
      glycosylation sites in that loop were either preserved or they were mutated to
      produce a deglycosylated CFTR (dgCFTR). Tagged CFTRs were expressed in HeLa
      cells, and their cAMP-sensitive Cl permeability was assayed using the halide
      sensitive fluorophore SPQ. CFTRs containing the M2 epitope showed halide
      permeability responses to cAMP, whereas cells expressing CFTR with the
      hemagglutinin (HA) tag showed little or no cAMP response. Xenopus oocytes
      expressing dgCFTR, with or without the M2 epitope, showed Cl conductance
      responses that were 20% of the wild-type response, whereas M2-tagged constructs
      retaining the glycosylation sites responded like wild-type CFTR. External M2
      tagged CFTR was detected in the surface membrane of nonpermeabilized cells. The
      surface expression of the mutant M2-tagged CFTRs correlated with processing of
      these mutants (Gregory et al. Mol. Cell. Biol. 11:3886-3893, 1991). M2-901/CFTR
      is a useful reporter for the trafficking of wild-type and mutant CFTRs to the
      cell surface.

PMID- 8572188
TI  - Impaired development of interstitial cells and intestinal electrical rhythmicity
      in steel mutants.
AB  - Electrical rhythmicity in the gastrointestinal tract may originate in
      interstitial cells of Cajal (IC). Development of IC in the small intestine is
      linked to signaling via the tyrosine kinase receptor, c-kit. IC express c-kit
      protein, and disruption of c-kit signaling causes breakdown in IC networks and
      loss of slow waves. We tested whether mutations in steel factor, the ligand for c
      kit, affect the development of IC networks. IC were found in the region of the
      myenteric plexus (IC-MY) in mice with steel mutations (i.e., Sl/Sld) at 5-10 days
      postpartum, but these cells formed an abnormal network. IC-MY were not observed
      in adult Sl/Sld animals. IC in the deep muscular plexus (IC-DMP) appeared normal
      in Sl/Sld animals. Electrical slow waves, normally present in the small
      intestine, were absent in Sl/Sld animals (10-30 days postpartum). Neural inputs
      were intact in Sl/Sld animals. Steel factor appears important for the development
      of certain classes of IC, and IC-MY appear to be involved in the generation of
      electrical rhythmicity in the small intestine.

PMID- 8572189
TI  - Insulin increases blood volume in human skeletal muscle: studies using [15O]CO
      and positron emission tomography.
AB  - High insulin concentrations increase blood flow in the leg, but it is unknown
      whether this effect is associated with a change in muscle blood volume. In the
      present study, we used positron emission tomography combined with inhalation of
      [15O]carbon monoxide to quantitate the effect of insulin on skeletal muscle blood
      volume in humans. The reproducibility of the method was determined from two
      consecutive measurements performed in the basal state in five normal subjects.
      The coefficient of variation of the repeated measurements was 3.0 +/- 1.8%. In 14
      normal subjects [age 35 +/- 3 yr, body mass index 24.9 +/- 1.3 (SE) kg/m2],
      skeletal muscle blood volume was determined in the femoral region in the basal
      state and during euglycemic hyperinsulinemia (serum insulin 3,200 +/- 190
      pmol/l). The mean muscle blood volume was 3.3 +/- 0.1 ml/0.1 kg muscle in the
      basal state. Insulin increased muscle blood volume by 9 +/- 2% to 3.6 +/- 0.2
      ml/0.1 kg muscle (P < 0.01). The rate of whole body glucose uptake was 53 +/- 6
      mumol.kg-1.min-1 and correlated with muscle blood volume during insulin
      stimulation (r = 0.65, P < 0.02). We conclude that high insulin concentrations
      exert a true vasodilatory effect in human skeletal muscle.

PMID- 8572190
TI  - Effects of aging on glucose regulation during wakefulness and sleep.
AB  - Glucose intolerance, reduced sleep efficiency, and disturbed circadian
      rhythmicity occur in aging. In normal young subjects, glucose regulation is
      modulated by sleep and circadian rhythmicity. To examine age-related alterations
      in the temporal pattern of glucose tolerance and insulin secretion, eight
      modestly overweight healthy older men, eight weight-matched young men, and six
      young lean men were studied during constant glucose infusion for 53 h. Levels of
      glucose, insulin, C-peptide, and growth hormone (GH) were measured every 20 min.
      Rates of insulin and GH secretion were calculated by deconvolution. In older
      volunteers, sleep ws shallow and more fragmented than in young subjects but was
      nevertheless associated with robust glucose elevations. However, postsleep
      increases of insulin secretion were markedly dampened. During wakefulness, the
      normal morning-to-evening increase in glucose was preserved in the elderly, but
      insulin secretion failed to increase proportionately. Thus decreased glucose
      tolerance in aging is associated with insulin resistance and also with a relative
      insensitivity of the beta-cell to the modulation of glucose regulation by sleep
      and circadian rhythmicity.

PMID- 8572191
TI  - Comparative metabolism of plasminogen glycoforms I and II in the alloxan-diabetic
      rabbit.
AB  - The metabolism of plasminogen glycoforms I and II was measured in alloxan-induced
      diabetic and in age-matched control rabbits. Radiolabeled plasminogen I and II
      were degraded significantly more slowly in diabetic compared with control
      rabbits; plasminogen II [half-time (T1/2), 1.31 days] was degraded faster than
      plasminogen I (T1/2), 1.86 days) in diabetic rabbits and in control rabbits
      (T1/2, 1.18 and 1.58 days, respectively). From the catabolic rates and relative
      quantities in plasma, we calculated that approximately four molecules of
      plasminogen II were degraded for one molecule of plasminogen I in the diabetic
      and control rabbits. To verify this later observation, plasminogen I and II
      production by diabetic rabbit livers was compared with that by the control livers
      in vitro. During perfusion with [3H]leucine, 3H-labeled protein was released more
      slowly from diabetic than from control livers, but no quantitative difference in
      total plasminogen yield between diabetic and control livers was found.
      Nevertheless, plasminogen II was produced 0.7 +/- 0.4 and 4.3 +/- 0.3 times
      faster than plasminogen I by diabetic and control livers, respectively.
      Plasminogen metabolism in the diabetic rabbit did not differ qualitatively from
      that in the control rabbit except that catabolism was slowed.

PMID- 8572192
TI  - Local concentrations of macrophage colony-stimulating factor mediate osteoclastic
      differentiation.
AB  - Macrophage colony-stimulating factor (M-CSF) is essential for differentiation of
      osteoclasts and macrophages from a common bone marrow precursor. Using ST-2
      stromal cell/murine bone marrow coculture, we studied the effects of increasing
      amounts of M-CSF on differentiation of macrophages and osteoclasts. Addition of
      exogenous M-CSF caused a dose-dependent 98% decrease in tartrate-resistant acid
      phosphatase (TRAP)-positive multinucleated cells, accompanied by a 2.5-fold
      increase in nonspecific esterase-staining macrophages. Similar decrease in
      osteoclastic functional activity, including 125I-labeled calcitonin binding and
      calcitonin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production,
      were observed. Addition of exogenous M-CSF beyond 6 days in coculture had a
      decreasing ability to inhibit osteoclast formation, suggesting that M-CSF exerts
      its effects early in osteoclast differentiation, during the proposed
      proliferative phase of osteoclast formation. Similarly, early addition of
      neutralizing anti-M-CSF inhibited osteoclast formation, with diminishing effects
      beyond day 9. These results suggest that local high concentrations of M-CSF may
      influence the early determination of terminal differentiation into either
      macrophages or osteoclasts.

PMID- 8572193
TI  - Effect of physical exercise on glycogen turnover and net substrate utilization
      according to the nutritional state.
AB  - To determine the metabolic effects of a single bout of exercise performed after a
      meal or in the fasting state, nine healthy subjects were studied over two 8-h
      periods during which net substrate oxidation was monitored by indirect
      calorimetry. On one occasion, exercise was performed 90 min after ingestion of a
      meal labeled with [U-13C]glucose [protocol meal-exercise (M-E)]. On the second
      occasion, exercise was performed after an overnight fast and was followed 30 min
      later by ingestion of an identical meal [protocol exercise-meal (E-M)]. Energy
      balances were similar in both protocols, but carbohydrate balance was positive
      (42.2 +/- 5.1 g), and lipid balance was negative (-11.1 +/- 2.0) during E-M,
      whereas they were nearly even during M-E. Total glycogen synthesis was calculated
      as carbohydrate intake minus oxidation of exogenous 13C-labeled carbohydrate
      (calculated from 13CO2 production). Total glycogen synthesis was increased by 90%
      (from 47.6 +/- 3.8 to 90.7 +/- 5.4 g, P < 0.0001) during E-M vs. M-E. Endogenous
      glycogen breakdown was calculated as net carbohydrate oxidation minus oxidation
      of exogenous carbohydrate and was increased by 44% (from 35.8 +/- 5.6 to 51.7 +/-
      6.6 g, P < 0.004) during E-M. It is concluded that exercise performed in the
      fasting state stimulates glycogen turnover and fat oxidation.

PMID- 8572194
TI  - Quantitation of hepatic glucose fluxes and pathways of hepatic glycogen synthesis
      in conscious mice.
AB  - Mice were studied with the euglycemic hyperinsulinemic and the hyperglycemic
      clamp techniques after a 6-h fast: 1) euglycemic (6.7 +/- 0.2 mM)
      hyperinsulinemia (approximately 800 microU/ml); 2) hyperglycemic (15.3 +/- 0.4
      mM) hyperinsulinemia (approximately 800 microU/ml). All mice received an infusion
      of [3-3H]glucose and [U-14C]lactate. Basal hepatic glucose production (HGP)
      averaged approximately 170 mumol.kg-1.min-1 in both groups. During euglycemic and
      hyperglycemic hyperinsulinemia, HGP decreased by 53% (to 76.7 +/- 11.1 mumol.kg
      1.min-1; P < 0.01) and 74% (to 43.3 +/- 7.2 mumol.kg-1.min-1; P < 0.01),
      respectively. Hyperglycemia increased glucose cycling (by 2.1-fold; P < 0.01) and
      the contribution of gluconeogenesis to HGP (88 vs. 43%; P < 0.01) while
      decreasing that of glycogenolysis (12 vs. 57%; P < 0.01). The percentage of
      neosynthetized hepatic glycogen formed via the direct pathway was markedly
      increased during hyperglycemia (53 +/- 2% vs. 23 +/- 3%; P < 0.01): These data
      indicate that the assessment of hepatic glucose fluxes can be accomplished in
      conscious unrestrained mice and that, in the presence of hyperinsulinemia,
      hyperglycemia causes 1) a further inhibition of HGP mainly via inhibition of
      glycogenolysis and increase in hepatic glucose cycling; and 2) about a fivefold
      stimulation in the direct pathway of hepatic glycogen formation.

PMID- 8572195
TI  - Effect of blood flow on muscle lactate release studied in perfused rat hindlimb.
AB  - The influence of blood flow on muscle lactate and H+ release as well as muscle
      glyconeogenesis was studied in the perfused rat hindlimb. After 2 min of
      supramaximal stimulation the perfusate flow rate was 7 (F7), 12 (F12), or 18
      (F18) ml/min for 30 min. Perfusate samples were drawn frequently and muscle
      samples were obtained before stimulation, immediately after stimulation, and at
      3, 10, and 30 min of recovery from soleus, white gastrocnemius (WG) and red
      gastrocnemius. During the first 5 min of recovery lactate release was 35-39%
      lower (P < 0.05) in F7 than in F12 and F18 but with no differences in total
      release during recovery. In F7 the concentration of lactate was higher (P < 0.05)
      in soleus after 10 min (18-20%) and in WG after 30 min (63-67%) than in F12 and
      F18. During the first 2 min of recovery H+ release was 23-34% lower (P < 0.05) in
      F7 than in F12 and F18. The difference between H+ and lactate release was larger
      (P < 0.05) in F7 than in F12 and F18 from 3 to 10 min and from 5 to 10 min of
      recovery, respectively. Muscle glycogen concentrations after 30 min of recovery
      were independent of flow in each of the muscles. The present data suggest that 1)
      in the range of blood flow rates from 0.61 to 0.92 ml.min-1.g-1, lactate and H+
      release are independent of the flow rate, whereas at a lower flow rate (0.36
      ml.min-1.g-1) release of these substances is decreased; 2) low blood flow
      influences lactate efflux more than H+ release; and 3) muscle glyconeogenesis
      from lactate is of minor importance.

PMID- 8572196
TI  - Regulation of glucose transport and GLUT-1 expression by iron chelators in muscle
      cells in culture.
AB  - Possible association between the degree of iron load and glucose metabolism has
      been postulated by both in vivo and in vitro studies. Because skeletal muscle
      plays a major role in whole body glucose utilization, we evaluated the effect of
      iron chelators deferoxamine (DFO) and bipyridyl (Bip) on glucose metabolism and
      transport in cultured L6 muscle cells. Bip (0.1 mM) or DFO (0.5 mM) added for 24
      h to the culture medium increased glucose consumption, lactate production, and
      [14C]glucose incorporation into glycogen by approximately twofold. 2-Deoxy
      glucose uptake by L6 myotubes increased time dependently, reaching a 5-fold and
      2.5-fold increase after 12 h for Bip and DFO, respectively. Insulin induced a 2.5
      fold increase in glucose uptake in untreated cells, which was additive to the
      chelator's effect. Iron chelator-induced glucose transport stimulation was
      inhibited by cycloheximide (2.5 micrograms/ml), indicating dependence on de novo
      protein synthesis. Increases in GLUT-1 protein and mRNA concentration, without
      changes in GLUT-4, were found to be responsible for iron chelator effects. We
      conclude that L6 cells adapt to reduction in iron availability by increasing
      glucose utilization through an enhanced expression of GLUT-1, without losing
      their physiological response to insulin.

PMID- 8572197
TI  - Effect of training on epinephrine-stimulated lipolysis determined by
      microdialysis in human adipose tissue.
AB  - Trained humans (Tr) have a higher fat oxidation during submaximal physical work
      than sedentary humans (Sed). To investigate whether this reflects a higher
      adipose tissue lipolytic sensitivity to catecholamines, we infused epinephrine
      (0.3 nmol.kg-1.min-1) for 65 min in six athletes and six sedentary young men.
      Glycerol was measured in arterial blood, and intercellular glycerol
      concentrations in abdominal subcutaneous adipose tissue were measured by
      microdialysis. Adipose tissue blood flow was measured by 133Xe-washout technique.
      From these measurements adipose tissue lipolysis was calculated. During
      epinephrine infusion intercellular glycerol concentrations were lower, but
      adipose tissue blood flow was higher in trained compared with sedentary subjects
      (P < 0.05). Glycerol output from subcutaneous tissue (Tr: 604 +/- 322 nmol.100 g
      1.min-1; Sed: 689 +/- 203; mean +/- SD) as well as arterial glycerol
      concentrations (Tr: 129 +/- 36 microM; Sed: 119 +/- 56) did not differ between
      groups. It is concluded that in intact subcutaneous adipose tissue epinephrine
      stimulated blood flow is enhanced, whereas lipolytic sensitivity to epinephrine
      is the same in trained compared with untrained subjects.

PMID- 8572198
TI  - Postprandial free fatty acids stimulate activity of human corticosteroid binding
      globulin.
AB  - The effect of postprandial variation of free fatty acids (FFA) on serum
      corticosteroid binding globulin (CBG) properties and cortisol (hydrocortisone)
      concentrations were explored in 11 women (20-30 yr) during 8 h after an oral load
      of tallow (26% C16:0, 18% C18:0, and 43% C18:1), oleic-sunflower (oleic-SF; 73%
      C18:1), sunflower (SF; 67% C18:2), and mixed oil (MO; 39% C18:1 and 48% C18:2).
      Serum FFA increased little after SF and MO but more than doubled in the late
      postprandial period (6 and 8 h) after oleic-SF (due to monounsaturated FFA) or
      tallow (due to saturated and monounsaturated FFA). CBG concentrations remained
      unchanged, but in relation with the postprandial elevation of serum FFA, CBG
      binding activity was increased after tallow or oleic-SF as a result of a combined
      two- to threefold increase in affinity constant and a 50% reduction in binding
      sites. Immunological and in vitro binding studies showed the changes in CBG
      behavior to be conformational and to be mediated mainly by monounsaturated FFA,
      especially C18:1. The modifications of CBG properties were associated with
      sustained high concentrations of cortisol (suppression of midday decrease) 6 and
      8 h after tallow or oleic-SF. Thus dietary FFA may have an impact on
      bioavailability of glucocorticoids.

PMID- 8572200
TI  - Interleukin-1 alpha stimulates dopamine release by activating type II protein
      kinase A in PC-12 cells.
AB  - A recent study from this laboratory [A. R. Gwosdow, N. A. O'Connell, and A. B.
      Abou-Samra. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E461-E466, 1992] showed
      that the inflammatory mediator interleukin-1 alpha (IL-1 alpha) stimulates
      catecholamine release from primary cultures of rat adrenal cells. The present
      studies were conducted to determine whether 1) IL-1 alpha stimulates
      catecholamine/dopamine release from the adrenal medullary cell line PC-12 and 2)
      the adenosine 3',5'-cyclic monophosphate (cAMP)-protein kinase A (PKA) pathway is
      involved in IL-1 alpha-induced dopamine release from PC-12 cells. The results
      indicate that IL-1 alpha significantly (P < 0.05) elevated dopamine release after
      a 24-h incubation period. IL-1 alpha did not stimulate cAMP accumulation at any
      time period between 5 min and 2 h. In contrast, forskolin-treated cells elevated
      (P < 0.05) intracellular cAMP levels and increased dopamine release. Because IL-1
      alpha did not affect cAMP accumulation, the effect of IL-1 alpha on PKA activity
      was investigated. IL-1 alpha increased (P < 0.05) PKA activity at 15 and 30 min
      and returned to control levels by 1 h. Forskolin also increased (P < 0.05) PKA
      activity. The type of PKA activated (P < 0.05) by IL-1 alpha was type II PKA. In
      contrast, forskolin activated (P < 0.05) type I and type II PKA. Inhibition of
      PKA with the PKA inhibitor H-8 blocked PKA activity and dopamine secretion by
      both IL-1 alpha and forskolin in PC-12 cells. These observations demonstrate that
      1) IL-1 alpha stimulated dopamine release from PC-12 cells by activating PKA, 2)
      the mechanism of IL-1 alpha activation of PKA does not involve detectable
      increases in intracellular cAMP accumulation, and 3) IL-1 alpha activates type II
      PKA, which is used by IL-1 alpha to stimulate dopamine secretion from PC-12
      cells.

PMID- 8572199
TI  - Regulation of bioactive and immunoreactive ACTH secretion by CRF and AVP in sheep
      fetuses.
AB  - The purpose of this study was to determine the effects of corticotropin-releasing
      factor (CRF) or arginine vasopressin (AVP) on the secretion of bioactive
      adrenocorticotropic hormone (bACTH) and immunoreactive ACTH (iACTH), the latter
      being measured by radioimmunoassay and separate two-site immunoradiometric assays
      for ACTH-(1-39) and ACTH precursors. Experiments were performed on chronically
      catheterized fetal sheep at 0.70 (n = 9) and 0.90 (n = 8) gestation. Each fetus
      received a 15-min infusion of CRF, AVP, or saline on 3 consecutive days. Blood
      was obtained before and 15 and 60 min after the infusion began. CRF significantly
      increased iACTH at 15 (younger group) and 60 min (both groups). CRF significantly
      increased bACTH and the bACTH-to-iACTH ratio (bACTH/iACTH) in both groups at 15
      and 60 min. AVP significantly increased iACTH, bACTH, and bACTH/iACTH in both
      groups at 15 min. In two subgroups (n = 4/subgroup), CRF significantly increased
      ACTH-(1-39) and ACTH precursors at 15 and 60 min. CRF increased the ratio of ACTH
      (1-39) to ACTH precursors [ACTH-(1-39)/ACTH precursors] at 15 (younger group) and
      60 min (both groups). AVP increased ACTH-(1-39), ACTH precursors, and ACTH-(1
      39)/ACTH precursors in both groups at 15 min. These findings show that both CRF
      and AVP can stimulate the secretion of bACTH, ACTH-(1-39), and ACTH precursors at
      0.70 and 0.90 gestation. The proportional increments in bACTH/iACTH and ACTH-(1
      39)/ACTH precursors suggest that CRF and AVP evoke selective increases in bACTH
      and ACTH-(1-39).

PMID- 8572201
TI  - Transgenic mice expressing IFN-gamma in pancreatic beta-cells are resistant to
      streptozotocin-induced diabetes.
AB  - In 28 adult Ins-IFN-gamma transgenic mice, injection of high doses of
      streptozotocin (STZ; first injection, 300 microgram/g body weight; second
      injection, 200 microgram/g body weight 4 h later) failed to induce severe
      hyperglycemia. To the contrary, 28 BALB/c mice developed diabetes mellitus after
      identical injections of STZ. Because the STZ-induced islet damage was partially
      inhibited in Ins-IFN-gamma transgenic mice, their glycemia levels became normal 4
      days after STZ administration. Both transgenic and BALB/c mice lost weight after
      receiving STZ, but the body weights of transgenic mice then returned to
      pretreatment levels in a nearly parallel manner with the glycemia. Immunolabeling
      with insulin identified an unusual spreading pattern of insulin immunoreactivity.
      Ultrastructural observations confirmed that beta-cell necrosis and degranulation
      were more severe in STZ-treated BALB/c than in Ins-IFN-gamma transgenic mice.
      Moreover, regeneration of pancreatic duct cells and islet neogenesis were
      observed in the transgenic mice. Therefore, after STZ treatment, the Ins-IFN
      gamma transgenic mice apparently were resistant to the induction of severe
      diabetes, whereas their BALB/c age-matched counterparts succumbed to the disease.

PMID- 8572202
TI  - Effect of AVP and oxytocin on insulin release: involvement of V1b receptors.
AB  - We used a number of receptor antagonists to determine which receptors mediate the
      effect of arginine vasopressin (AVP) and oxytocin (OT) on insulin release. We
      found that OT (10(-7) M) and AVP (10(-8) M) increased insulin release from the
      perfused rat pancreas with similar magnitude. The antagonist with potent V1b
      receptor-blocking activity, dP[Tyr(Me)2]AVP (10(-7) M), abolished the effect of
      OT and AVP, whereas the highly selective OT receptor antagonist L-366,948 (10(-6)
      M) did not change the effect of OT, nor did a V1a receptor antagonist,
      d(CH2)5[Tyr(Me)2]AVP (10(-7) M), change the effect of AVP. The insulin-releasing
      potency of OT was estimated as 9-fold less than that of AVP in RINm5F cells.
      Selected AVP and OT antagonists were used to study their antagonism on AVP- and
      OT-induced insulin release from RINm5F cells, and the order of potencies of
      antagonists was estimated as dP[Tyr(Me)2]AVP > d(CH2)5[D-Phe2,Ile4]AVP > SR-49059
      > d(CH2)5[Tyr(Me)2]AVP > desGly9d(CH2)5[Tyr(Et)2]VAVP (WK-3-6) approximately L
      366,948. These results were consistent with the V1b receptor antagonistic
      activities of the antagonists. d[D-3-Pal]VP, a V1b receptor agonist, increased
      insulin release dose dependently (10(-9) to 10(-6) M), and this effect was
      antagonized by dP[Tyr(Me)2]AVP but not by WK-3-6 (10(-6) M). These results
      suggested that the stimulatory effect of both OT and AVP on insulin release from
      beta-cells may be mediated by V1b, but not by V1a or OT receptors.

PMID- 8572203
TI  - Cyclical variation of plasma lipids, apolipoproteins, and lipoprotein(a) during
      menstrual cycle of normal women.
AB  - We report herein the effects of cyclical variations of endogenous sex steroids
      during the menstrual cycle on plasma lipids and apolipoproteins (apo) in normal
      women. We examined 16 normal women (age range 25-36 yr) with normal menstrual
      cycles of 28-31 days. The study covered the period from the 1st day of a
      menstrual phase (basal) until the 1st day of the following menstrual phase.
      During the study all women maintained a normolipidic diet (30% fat). Plasma total
      cholesterol and low-density-lipoprotein cholesterol were significantly higher
      than basal in the preovulatory phase until progesterone started to increase in
      the postovulatory phase [day +8 from luteinizing hormone (LH) surge]. High
      density-lipoprotein cholesterol was significantly higher than basal from day -1
      to the day after LH surge, whereas plasma apoAI levels were significantly higher
      from day -8 to day +8 (from LH surge). Plasma apo(a) increased significantly
      during the luteal phase in four women characterized by a single S4 band and lower
      basal plasma levels of apo(a). Our results indicate that endogenous female sex
      steroids have significant effects on the circulating levels of plasma lipids and
      apolipoproteins, including apo(a). More work needs to be done to elucidate the
      significance of the observed apo(a) changes, and the different phases of the
      menstrual cycle must be taken into account when evaluating the lipidic risk
      profile in premenopausal women.

PMID- 8572204
TI  - Impact of sampling technique on appraisal of pulsatile insulin secretion by
      deconvolution and cluster analysis.
AB  - Little is known about the optimal experimental conditions for assessing pulsatile
      insulin secretion in vivo. To address this, we employed a recently validated
      canine model (n = 12) to determine the consequences of 1) sampling from the
      systemic circulation (SC) vs. the portal vein (PV), 2) sampling intensity and
      duration, and 3) deconvolution vs. cluster analysis on assessing pulsatile
      insulin secretion. PV vs. SC sampling resulted in a approximately 40% higher
      pulse frequency by deconvolution (9.0 +/- 0.5 vs. 6.6 +/- 0.9 pulses/h, P < 0.02)
      and cluster analysis (7.5 +/- 0.3 vs. 5.6 +/- 0.6 pulses/h, P < 0.01) due to a
      higher signal-to-noise ratio (19 +/- 4.8 PV vs. 12 +/- 1.8 SC). PV sampling also
      disclosed a higher calculated contribution of the pulsatile vs. nonpulsatile mode
      of delivery to total insulin secretion (57 +/- 4 vs. 28 +/- 5%, P < 0.001).
      Analysis of the relevance of sampling intensity revealed that 1-min data yielded
      a markedly higher estimate of pulse frequency with PV sampling than 2-min data
      (9.0 +/- 0.5 vs. 5.4 +/- 0.5, P < 0.02, deconvolution; 7.5 +/- 0.3 vs. 4.3 +/-
      0.6 pulses/h, P < 0.001, cluster). Optimal sampling duration was shown to be 40
      min or more. We conclude that the resolving power of the analytical tool, the
      anatomic site of blood withdrawal, the frequency of blood sampling, and the
      duration of the total observation interval all significantly influence estimated
      insulin secretory pulse frequency and the fraction of insulin secreted in pulses.
      With the assumption that PV 1-min insulin data constitute the "gold standard,"
      our in vivo inferences of 7.5-9.0 insulin pulses/h closely recapitulate in vitro
      islet secretory activity.

PMID- 8572205
TI  - A model for multiple subcutaneous insulin injections developed from individual
      diabetic patient data.
AB  - Many diabetic patients taking multiple subcutaneous insulin injections cannot
      adjust their dosage appropriately to maintain blood glucose within a normal
      range. It is hard to predict how dosage changes and physiological fluctuations
      affect insulin levels and subsequently glucose control. To examine these issues,
      we have developed a model representing the link between dosage and blood insulin
      levels. Our model adequately predicts insulin concentrations for individual
      patients and could be incorporated into an overall glucose-insulin
      representation. More importantly, parameter and sensitivity analysis results
      highlight insulin kinetic features that are difficult to isolate in a clinical
      setting and that may significantly influence glucose dynamics. For example, large
      interpatient variation, measured quantitatively by model parameters, emphasizes
      the need for individualized design of insulin regimens. Intrapatient variations
      are also large in some patients. Improved control for these patients may only be
      possible through more frequent sampling and control action. The sensitivity
      coefficient for absorption suggests a significant overlapping injection effect
      that is not considered in present patient management strategies.

PMID- 8572206
TI  - Age-dependent reduction in insulin secretion and insulin mRNA in isolated islets
      from rats.
AB  - Aging is an etiologic factor in non-insulin-dependent diabetes mellitus. To
      characterize the beta-cell abnormalities that occur with age, we investigated
      glucose-stimulated insulin release, pancreatic insulin content, and mRNA levels
      for islet-specific genes in aging Wistar rats. Ten minutes after glucose
      stimulation, 6-mo-old islets had approximately 40% more cells secreting insulin
      than 24-mo-old islets (P < 0.0001); after 1 h, 67 +/- 1.0% islets from 6-mo-old
      rats secreted insulin, compared with 51 +/- 3.5% from 24-mo-old rats (P <
      0.0001). The amount of insulin secreted by each beta-cell was also less in the
      older animals (P < 0.0001). Despite increases in islet size (P < 0.0001) and beta
      cell number (P < 0.0001) with age, whole pancreas insulin content showed that 24
      mo-old pancreas had less insulin than 6-mo-old pancreas (0.61 +/- 0.06 vs. 0.84
      +/- 0.08 microgram/mg pancreatic protein; P < 0.05). Finally, insulin mRNA levels
      declined to 50% of the newborn value in 24-mo-old islets (P < 0.0001), whereas
      glucagon mRNA levels showed a very modest decline with age. Somatostatin mRNA
      levels did not vary significantly. In summary, it appears that in Wistar rats
      there is a progressive decline in beta-cell activity with age. This decline may
      represent the biological features of the age-dependent risk of developing
      diabetes.

PMID- 8572207
TI  - Involvement of alpha 2-adrenoceptors in metabolic and hormonal responses to a
      mixed meal in beagle dogs.
AB  - The effects of alpha 2-adrenoceptor blockade or activation on glucose, insulin,
      free fatty acids (FFA), and glycerol responses to a mixed meal were studied in
      the beagle dog. The alpha 2-adrenoceptor antagonist deriglidole (1 mg/kg po),
      administered 45 min before feeding, significantly reduced glycemia and increased
      insulin, FFA, and glycerol levels. Although the alpha 2-adrenoceptor agonist UK
      14.304 (3 micrograms/kg sc), administered 15 min before feeding, had no effect
      per se, it completely blocked meal-induced insulin release, thus promoting a mild
      increase in glycemia, and prolonged the meal-induced FFA decrease. Deriglidole
      antagonized the reduction of insulin secretion and the hyperglycemia induced by
      UK-14.304. The meal-induced fall in FFA levels was still observed after
      deriglidole treatment and was markedly amplified when UK-14.304 was administered
      with deriglidole. These results suggest that, in the dog, insulin release and
      lipolysis are very sensitive to alpha 2-adrenoceptor stimulation. It is also
      suggested that the meal-evoked decrease in lipid mobilization results from an
      increase in alpha 2-adrenoceptor stimulation rather than from an increase in
      insulin secretion.

PMID- 8572208
TI  - Gut mucosal protein synthesis measured using intravenous and intragastric
      delivery of stable tracer amino acids.
AB  - We measured the rates of mucosal protein synthesis during the simultaneous
      delivery of [1-13C]leucine and [1-13C]valine delivered either intragastrically or
      intravenously to investigate any influence of the route of supply of the tracers.
      Dependent on the route, there were marked differences in the gradient of labeling
      between the plasma and intramucosal leucine and valine; i.e., for intravenous
      tracers the ratio was 1.73 +/- 0.16, but for intragastric tracers it was 0.65 +/-
      0.12 (P < 0.05). Incorporation of intravenous tracer into mucosal protein was
      linear with time, and irrespective of tracer route, the calculated fractional
      rates of protein synthesis were identical when based on the intracellular
      labeling of the leucine or valine tracer, i.e., with intravenous 2.58 +/- 0.32%/h
      and with intragastric 2.45 +/- 0.36%/h. The results demonstrate that a robust and
      reproducible method of measurement of gastrointestinal mucosal protein synthesis
      has been developed and that use of either intragastric or intravenous routes of
      tracer administration gives comparable results. The high rates measured suggest
      that the gastrointestinal mucosa contributes substantially to whole body protein
      synthesis in normal healthy subjects.

PMID- 8572209
TI  - Fourth ventricle injection of corticotropin-releasing factor and gastric emptying
      of glucose during gastric fill.
AB  - The effect of corticotropin-releasing factor (CRF) administered into the fourth
      ventricle on the gastric emptying of a 12-ml intragastric infusion of 12.5% D
      glucose was examined in nondeprived male rats. All three CRF doses tested (10,
      100, and 1,000 pmol) significantly reduced (by 28, 29, and 44%, respectively) the
      amount of glucose emptied from the stomach at the end of the 12-min (1.0 ml/min)
      gastric infusion interval. The 10 pmol effective dose is the lowest yet reported
      to influence gastric emptying. The receptor specificity of the exogenous CRF
      (1,000 pmol) effect was demonstrated by its complete blockade by preinjection of
      alpha-helical CRF-9-41 (10 nmol) into the fourth ventricle. Injection of the
      antagonist alone, however, did not affect glucose emptying, indicating little
      activation of the targeted receptors under the present nonstressful, baseline
      conditions. Our results suggest that of the central CRF receptor systems that
      influence gastric emptying, those in the caudal brain stem, targeted by fourth
      ventricular injection, may be of particular importance.

PMID- 8572210
TI  - Molecular mechanisms of hepatic bile salt transport from sinusoidal blood into
      bile.
AB  - An increasingly complex picture has emerged in recent years regarding the bile
      salt transport polarity of hepatocytes. At the sinusoidal (or basolateral) plasma
      membrane two bile salt-transporting polypeptides have been cloned. The Na(+)
      taurocholate-cotransporting polypeptide (Ntcp) can account for most, if not all,
      physiological properties of the Na(+)-dependent bile salt uptake function in
      mammalian hepatocytes. The cloned organic anion-transporting protein (Oatp1) can
      mediate Na(+)-independent transport of bile salts, sulfobromophthalein, estrogen
      conjugates, and a variety of other amphipathic cholephilic compounds. Hence,
      Oatp1 appears to correspond to the previously suggested basolateral multispecific
      bile sale transporter. Intracellular bile salt transport can be mediated by
      different pathways. Under basal bile salt flux conditions, conjugated trihydroxy
      bile salts bind to cytoplasmic binding proteins and reach the canalicular plasma
      membrane predominantly via cytoplasmic diffusion. More hydrophobic mono- and
      dihydroxy and high concentrations of trihydroxy bile salts associate with
      intracellular membrane-bound compartments, including transcytotic vesicles,
      endoplasmic reticulum (ER), and Golgi complex. A facilitated bile salt diffusion
      pathway has been demonstrated in the ER. The exact role of these and other (e.g.,
      lysosomes, "tubulovesicular structures") organelles in overall vectorial
      transport of bile salts across hepatocytes is not yet known. Canalicular bile
      salt secretion is mediated by two ATP-dependent transport systems, one for
      monovalent bile salts and the second for divalent sulfated or glucuronidated bile
      salt conjugates. The latter is identical with the canalicular multispecific
      organic anion transporter, which also transports other divalent organic anions,
      such as glutathione S-conjugates. Potential dependent canalicular bile salt
      secretion has also been suggested to occur, but its exact mechanism and
      physiological significance remain unclear, since a potential driven bile salt
      uptake system has also been identified in the ER. Hypothetically, and similar to
      changes in cell volume, the intracellular potential could also play a role in the
      regulation of the number of bile salt carriers at the canalicular membrane and
      thereby indirectly influence the maximal canalicular bile salt transport capacity
      of hepatocytes.

PMID- 8572211
TI  - Somatostatin receptors.
AB  - Somatostatin induces its biological actions by activating a family of receptor
      subtypes. The recent cloning of five somatostatin receptor subtypes has led to
      the development of subtype-selective agonists. These compounds are revealing
      distinct functions of the individual receptor subtypes. Mutagenesis studies have
      revealed domains of several of the receptors involved in specific recognition of
      somatostatin analogues. Molecular modeling of both of these ligand-binding
      domains and the constrained somatostatin analogues that they interact with may
      lead to the development of nonpeptide somatostatin drugs that could be useful in
      the treatment of tumors and various metabolic, gastrointestinal, and central
      nervous system disorders.

PMID- 8572212
TI  - Octreotide reduces perception of rectal electrical stimulation by spinal afferent
      pathway inhibition.
AB  - Octreotide reduces perception of rectal distension in normal volunteers and
      irritable bowel patients. To localize octreotide's site of action, perceptual and
      evoked potential responses to rectal electrical stimulation were tested in seven
      normal volunteers after double-blind octreotide (100 micrograms 2) or placebo.
      After octreotide, the currents needed to elicit threshold perception of square
      wave impulses delivered to the rectum were 29% higher than after placebo. When
      electrical stimulation was delivered at constant currents 50% above threshold,
      rectal perception scores were significantly reduced after octreotide compared
      with placebo. Rectal electrical stimulation led to characteristic and
      reproducible cerebral evoked potentials. Octreotide had no effect on latencies,
      but reduced peak-to-peak amplitudes by 35% compared with placebo. Rectal
      electrical stimulation also led to characteristic and reproducible spinal evoked
      potentials. Octreotide had no effect on spinal latencies, but reduced peak-to
      peak amplitudes by 51%. In conclusion, octreotide reduces perception of rectal
      electrical stimulation, which is associated with inhibition of cerebral and
      spinal evoked potential amplitude, indicating effects on spinal afferent
      pathways.

PMID- 8572213
TI  - Alterations in intestinal bacterial flora modulate the systemic cytokine response
      to hemorrhagic shock.
AB  - To test the hypothesis that the resident gut flora plays an active role in
      modulating the cytokine response to hemorrhagic shock, plasma levels of
      interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured from the
      following three groups of rats before, immediately after, and 3, 8, or 24 h post
      hemorrhagic shock (90 min at 30 mmHg)/sham shock: 1) rats with a normal gut flora
      (NF), 2) rats whose gut flora had been decontaminated with oral antibiotics (AD),
      and 3) rats with intestinal overgrowth with E. coli. In all three groups, portal
      and systemic TNF and IL-6 levels were 2- to 10-fold higher in the shock than the
      sham-shock rats (P < 0.05), with the highest TNF and IL-6 levels observed in the
      rats that were colonized with Escherichia coli (P < 0.05 vs. AD and NF). TNF
      levels were higher in the NF than the AD groups at 3 and 8 h postshock. The
      present study suggests that changes in the gut microflora modulate the systemic
      cytokine response to hemorrhagic shock with intestinal bacterial overgrowth
      leading to the greatest increase in plasma IL-6 and TNF levels.

PMID- 8572214
TI  - Trehalase gene expression during postnatal development of rabbit intestine and
      kidney: effects of glucocorticoids.
AB  - Rabbit trehalase is a 75-kDa glycosyl phosphatidylinositol-anchored glycoprotein
      of the microvillus membrane of the enterocyte and kidney proximal tubule
      epithelial cells. The purpose of this work was to try to elucidate the molecular
      basis of trehalase gene expression in intestine and kidney during normal
      postnatal development and after hydrocortisone injection in suckling rabbits.
      Trehalase cDNA isolated, sequenced, and characterized by J. Ruf, H. Wacker, P.
      James. M. Maffia, P. Seiler, G. Galand, A. Kieckebusch, G. Semenza, and N. Mantei
      (J. Biol. Chem. 265: 15034-15039, 1990) was used to quantify trehalase mRNA. To
      measure the amount of trehalase mRNA encoding for trehalase, poly(A)+ mRNA was
      isolated and analyzed by Northern blot hybridization. This cDNA hybridized to a
      1.8-kb mRNA in the small intestine and kidney. In developing rabbit intestine,
      after a slow decrease between 4 and 10 days, there is a sharp and parallel rise
      of both trehalase specific activity (28x) and mRNA (10x) between 10 and 30 days
      after birth. In contrast, in the kidney, between 4 and 30 days, the general
      developmental profile of both parameters is very different. There is an overall
      significant and parallel increase of both trehalase specific activity (3.3x) and
      mRNA (4.3x). In intestine the longitudinal gradient of trehalase activity and
      mRNA expression is different in adult and 16-day cortisol-treated suckling
      rabbits. In intestine, between 10 and 14 days, cortisol induces a coordinate
      increase of both trehalase activity (26x) and mRNA (19x), but at 16 days the two
      parameters diverge markedly. Daily injections of cortisol between 10 and 16 days
      do not induce significantly trehalase mRNA over controls at 16 days. In only 2
      days, between 14 and 16 days, there is a clear loss of trehalase mRNA
      responsiveness to glucocorticoids. On the contrary, in the kidney, daily
      injections of cortisol between 10 and 16 days have no significant effect on
      trehalase mRNA but induce a small and significant increase of trehalase specific
      activity at 16 days (1.8x). Therefore we conclude that, with respect to the
      distribution along the small intestine, normal development in kidney and
      intestine, and after induction with glucocorticoid in intestine, alteration in
      the steady-state levels of trehalase mRNA is a major mechanism for the regulation
      of trehalase gene expression.

PMID- 8572215
TI  - Confocal analysis of hepatocellular long-chain fatty acid uptake.
AB  - Transmembrane transport and cytosolic accumulation of fatty acids were
      investigated using confocal laser scanning microscopy (cLSM). A Zeiss LSM 310
      system was used to determine the uptake of the fluorescent fatty acid derivative
      12-(N-methyl)-N-[(7-nitrobenz-2-oxa-1,3- diazol-4-yl)amino]octadecanoic acid (12
      NBD stearate) (C18) in single rat hepatocytes. Uptake was a saturable process
      with a Michaelis-Menten constant value of 68 nM. Initial uptake velocity was
      dependent on extracellular presence of albumin and beta-lactoglobulin. Absence of
      albumin reduced uptake to 32 +/- 16% (P < 0.01) of control values. In the
      presence of unlabeled stearate, uptake of 12-NBD stearate was lowered to 49 +/-
      12% (P < 0.01). Ion substitution experiments showed no sodium dependency of
      uptake. Increase in membrane potential led to a pronounced accumulation of the
      fatty acid derivative within the plasma membrane and in the adjacent cytoplasmic
      compartment, whereas membrane depolarization had no effect on uptake rates. In
      separate experiments line scans through representative hepatocytes were analyzed
      to generate "x-t" plots. 12-NBD stearate showed a fluorescence pattern with
      prominent staining of the area of the plasma membrane and the adjacent cytoplasm,
      dependent on the presence of extracellular albumin. For the hepatocellular
      cytosolic accumulation process of 12-NBD stearate a diffusion constant of 22.2 +/
      6.2 x 10(-9) cm2/s was calculated. In contrast to the long-chain fatty acid
      derivative 12-NBD stearate, short (C5)- and medium (C11)-chain fatty acids
      revealed no membrane interaction with hepatocytes. Erythrocytes also lacked a
      membrane interaction process for 12-NBD stearate. In conclusion, it was
      demonstrated that cLSM is capable of directly evaluating the cellular fatty acid
      uptake process at a subcellular level.

PMID- 8572216
TI  - Intra-islet regulation of hormone secretion by glucagon-like peptide-1-(7--36)
      amide.
AB  - Glucagon-like peptide (GLP)-1-(7--36) amide, a peptide product of the
      posttranslational processing of pancreatic and intestinal proglucagon, has been
      shown to regulate insulin secretion. Monoclonal antibodies to glucagon and GLP-1
      (7--36) amide were generated to localize GLP-1-(7--36) amide in the pancreatic
      islets by immunocytochemistry and radioimmunoassay. GLP-1-(7--36) amide
      immunoreactivity was found in some, but not all, glucagon-containing alpha-cells.
      Displaceable receptor binding for GLP-1-(7--36) amide and nonamidated GLP-1-(7-
      37) on hormone secretion were investigated using isolated pancreatic islet
      preparations. GLP-1-(7--37) and -(7--36) amide significantly increased insulin
      and somatostatin release in the concentration range of 0.01-100 nM in 11.0 mM
      glucose. GLP-1-(7--37) and -(7--36) amide had no effect on glucagon secretion in
      the presence of 11.0 mM glucose. GLP-1-(7--36) amide was released from isolated
      islets in response to 2.25, 5.5, and 11.0 mM glucose. These results suggest that
      pancreatic GLP-1 may be important in the regulation of intra-islet hormone
      secretion.

PMID- 8572217
TI  - Sources of arginine for induced nitric oxide synthesis in the isolated perfused
      liver.
AB  - Hepatocytes can be stimulated to express high levels of inducible nitric oxide
      synthase (iNOS), which utilizes arginine for nitric oxide (NO) synthesis.
      Hepatocytes also synthesize and catabolize arginine, an intermediate in the urea
      cycle, raising the possibility that the urea pathway may provide substrate for
      hepatic NO synthesis. To identify the sources of arginine for iNOS, we measured
      the release of NO-2 + NO-3 and urea in isolated rat livers perfused in a
      recirculation model with a Krebs-Henseleit-bicarbonate buffer containing either
      no added amino acid, arginine, or precursors for urea synthesis. To induce iNOS
      expression, rats were injected with killed Corynebacterium parvum (C. parvum) or
      with endotoxin. In livers from C. parvum- and endotoxin-treated rats, we found
      that 1) an intracellular source of arginine exists that provides substrate to
      iNOS; 2) additional exogenous arginine increase NO synthesis, demonstrating that
      endogenous arginine is insufficient for maximal NO synthesis; and 3) an increase
      in the rate of endogenous arginine synthesis within the urea cycle is inefficient
      in increasing NO synthesis, demonstrating the independence of the two pathways in
      the liver.

PMID- 8572218
TI  - Absorption of epidermal growth factor occurs through the gastrointestinal tract
      and oral cavity in adult rats.
AB  - Introduction of radiolabeled epidermal growth factor (125I-EGF) by gavage or
      sublingual confinement resulted in a time-dependent uptake and systemic organ
      dissemination in the adult rat. Intact EGF was recovered primarily from the
      tongue, parotid, and sublingual/submandibular glands after administration by
      sublingual lozenge, whereas gastrointestinal administration resulted in 125I-EGF
      recovery primarily from plasma, stomach, and lung. Recovered radiolabeled EGF
      retained the ability to bind to the EGF receptor. Sialoadenectomy caused an
      increase in 125I-EGF in most tissues by both routes of administration. Thus, in
      the adult rat, at least two pathways exist for the uptake and distribution for
      salivary gland-derived EGF present in saliva. With further analyses, sublingual
      absorbance of EGF may therefore provide a potential delivery route for
      therapeutic use of growth factor, which avoids the hepatic destruction of EGF
      after oral administration.

PMID- 8572219
TI  - Genistein and tyrphostin 47 stimulate CFTR-mediated Cl- secretion in T84 cell
      monolayers.
AB  - The involvement of tyrosine phosphorylation in the regulation of epithelial cell
      Cl- secretion is unknown. Therefore, the purpose of these studies was to
      determine if tyrosine kinase activation was involved in the regulation of Cl-
      secretion, using the tyrosine kinase inhibitors, genistein and tyrphostin 47, and
      human intestinal epithelial cells (T84 cells) as an intestinal Cl- secretory
      model. Genistein rapidly but reversibly stimulated sustained apical Cl- secretion
      in monolayers of T84 cells without increasing intracellular cyclic nucleotides or
      Ca2+ levels. Tyrphostin 47 also stimulated Cl- secretion in T84 monolayers,
      although it was short-lived. Transfection experiments in 3T3 fibroblasts and IEC
      6 intestinal cells utilizing wild-type cystic fibrosis transmembrane conductance
      regulator (CFTR) showed that genistein and tyrphostin 47 stimulated 125I efflux
      only in CFTR-transfected cells and not in CFTR-negative cells. Thus genistein-
      and tyrphostin 47-stimulated Cl- secretion involved CFTR. Genistein also acted
      synergistically with the Ca(2+)- and protein kinase C-dependent acetylcholine
      analogue, carbachol, to stimulate Cl- secretion in T84 monolayers. However, the
      Cl- secretory response to saturating concentrations of the adenosine 3',5'-cyclic
      monophosphate (cAMP) agonist, forskolin, or the guanosine 3',5'-cyclic
      monophosphate (cGMP) agonist, Escherichia coli heat-stable enterotoxin, was not
      further enhanced by genistein. Although the mechanism of activation of Cl-
      secretion is unclear, these data suggest that tyrosine kinase activity limits
      basal Cl- secretion in T84 cells and that inhibition of T84 cell tyrosine
      kinase(s) stimulates apical membrane Cl- secretion, most likely through
      activation of the CFTR-Cl- channel. Moreover, genistein does not itself act
      through cAMP or cGMP elevation but appears to share a common Cl- secretory
      pathway with cyclic nucleotide-dependent agonists, whereas it augments the
      secretory responses to a Ca(2+)- and protein kinase C-dependent agonist.

PMID- 8572220
TI  - In vivo trafficking of nascent H(+)-K(+)-ATPase in rabbit parietal cells.
AB  - Protein metabolic labeling in vivo was used to determine a time course for
      trafficking of nascent H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase) from
      endoplasmic reticulum (ER) to mature tubulovesicles in parietal cells. Stomachs
      of cimetidine-treated rabbits were taken 15-90 min after injection of
      [35S]methionine/cysteine, and mucosal microsomes were fractionated on sucrose
      gradients for analysis by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, Western blot, and autoradiography. After 15 min, labeled alpha
      subunit peaked at approximately 1.14 g/ml, matching the distribution of the high
      mannose beta-subunit precursor, "pre-beta." After 30 min, most labeled alpha
      subunit was in a peak at approximately 1.10 g/ml, considered to be Golgi. By 90
      min, most labeled alpha-subunit was in a light peak, at approximately 1.07 g/ml,
      aligned with the major peak of total H(+)-K(+)-ATPase previously characterized as
      mature tubulovesicles. From material enriched in pre-beta, alpha-subunit was
      coprecipitated with pre-beta by a terminal mannose-specific lectin, Galanthus
      nivalis agglutinin, in the same ratio as the mature alpha:beta ratio. Thus alpha-
      and beta-subunits associated early in the ER. This is the first use of protein
      metabolic labeling to study early trafficking of the H(+)-K(+)-ATPase in vivo.
      The techniques may be usefully applied to examining changes in H(+)-K(+)-ATPase
      synthetic rate in response to various pharmacological treatments and studying the
      divergent pathways for nascent H(+)-K(+)- and Na(+)-K(+)-ATPases.

PMID- 8572221
TI  - Vagal and sympathetic components of the heart rate reflex in chronic portal vein
      stenosis.
AB  - The effects of portal hypertension and portosystemic shunting on autonomic
      components of the heart rate (HR) baroreflex and on skeletal muscle blood flow
      changes were investigated using the chronic portal vein-stenosed rat.
      Phenylephrine- and sodium nitroprusside-induced changes in mean arterial pressure
      (MAP), HR, and skeletal muscle conductance (SMC) were assessed before and after
      muscarinic or beta-adrenoceptor blockade. Stenosed rats had lower MAP than sham
      operated rats (90 +/- 3 vs. 81 +/- 2 mmHg, P < 0.05), and their portal pressure
      was higher (7.4 +/- 0.5 vs. 13.9 +/- 1.0 mmHg, P < 0.005). Phenylephrine pressor
      responses were reduced in stenosed animals, their associated bradycardic
      responses were enhanced [-1.912 +/- 0.109 vs. -1.427 +/- 0.148 beats per minute
      (bpm)/mmHg, P < 0.01], and their SMC responses were diminished. Methylatropine
      abolished bradycardic responses and enhanced pressor responses without affecting
      SMC. After propranolol, reflex bradycardic responses in stenosed rats were less
      than in shams (-0.492 +/- 0.085 vs. -0.738 +/- 0.058 bpm/mmHg, P < 0.01), and
      their pressor and SMC responses became indistinguishable from shams. In contrast,
      tachycardic responses to nitroprusside-induced hypotension before propranolol
      were impaired in stenosed rats (-1.492 +/- 0.114 vs. -2.225 +/- 0.347 bpm/mmHg, P
      < 0.05), and their SMC responses were reduced. Muscarinic blockade did not affect
      HR or SMC responses to hypotension in either stenosed or sham rats. beta
      Adrenoceptor blockade, however, prevented hypotension-induced tachycardia,
      enhanced nitroprusside depressor responses, and eliminated the between-group
      differences in SMC responses. These studies indicate that increased gain of the
      parasympathetic limb of the cardiac baroreflex was responsible for attenuated
      pressor responses to phenylephrine in portal vein-stenosed animals and that beta
      adrenoceptors contributed to skeletal muscle vascular hyporesponsiveness to
      phenylephrine in portal-vein stenosed animals. Altered beta-adrenoceptor function
      also appears to contribute to impaired chronotropic and skeletal muscle
      conductance responses to hypotension.

PMID- 8572222
TI  - Extracellular matrix incorporation of normal and NEM-alkylated fibronectin: liver
      and spleen deposition.
AB  - The incorporation of plasma fibronectin (pFn) into the extracellular matrix (ECM)
      is believed to influence tissue integrity, wound repair, and vascular
      permeability. In vitro, matrix assembly of Fn requires the binding of soluble Fn
      to cell-associated matrix assembly sites. Alkylation of human pFn (HFn) with N
      ethylmaleimide (NEM) prevents the initial binding of Fn to matrix assembly sites
      as well as its in vitro incorporation into the ECM as reflected by detergent
      insoluble 125I-labeled Fn (pool II Fn). We determined the kinetics of Fn matrix
      incorporation in tissue and whether NEM treatment of rat pFn (NEM-RFn) would
      limit its in vivo incorporation into ECM by analysis of pool I [deoxycholate
      (DOC) soluble] and pool II (DOC insoluble) 125I-Fn in tissues after its
      intravenous injection into rats. After intravenous injection, tissue
      incorporation of normal rat 125I-pFn was especially intense in liver and spleen,
      in agreement with the large amount of endogenous Fn detected in the matrices of
      these organs. Tissue deposition of plasma-derived 125I-RFn in liver and spleen
      peaked by 4 h, with significant (P < 0.01) loss over 24 h, indicating turnover of
      matrix Fn. Tissue localization of normal 125I-RFn in liver, lung, spleen, heart,
      and intestine was greater (P < 0.05) than 125I-NEM-RFn at 4 h. Normal HFn, but
      not NEM-HFn, was incorporated into tissues and colocalized with endogenous Fn in
      the matrix. To identify the cells mediating the intense incorporation of pFn into
      liver ECM, we compared matrix assembly of 125I-HFn by cultured fibroblasts,
      hepatocytes, and hepatic Kupffer cells. With fibroblasts, 125I-HFn in pool I
      reached steady state by 3 h, whereas 125I-HFn in pool II exceeded that in pool I
      by 6 h and continued to increase over 24 h. With hepatocytes, pool I 125I-HFn
      reached steady state by 1 h, and a progressive increase (P < 0.05) of 125I-HFn in
      pool II was observed over 24 h. Kupffer cells were not able to incorporate
      significant amounts of 125I-HFn into matrix. NEM-HFn displayed limited
      incorporation into ECM by both fibroblast and hepatocyte cultures. These novel
      observations suggest that the interaction of soluble pFn with matrix assembly
      sites is necessary to its in vivo incorporation into the ECM.

PMID- 8572223
TI  - Immunocytes and abnormal gastrointestinal motor activity during ileitis in dogs.
AB  - Infiltration of specific immunocytes and stimulation of abnormal gastrointestinal
      motor activity during ileal inflammation induced by mucosal exposure to ethanol
      and acetic acid were investigated in 17 dogs. Ileal inflammation significantly
      increased the frequency of giant migrating contractions (GMCs) and decreased the
      frequency of migrating motor complexes (MMCs). The frequency of retrograde giant
      contractions (RGCs) increased only on the day of ethanol and acetic acid
      treatment. Diarrhea, urgency of defecation, and apparent abdominal discomfort
      were related to the increased frequency of GMCs. Ileal inflammation also
      prolonged the duration of postprandial MMC disruption. Histological and
      immunohistochemical findings indicated transmural inflammation with marked
      increase in polymorphonuclear cells in the lamina propria and muscularis externa
      layers. Myeloperoxidase activity increased severalfold in both layers. Cells
      containing interleukin-2 receptor (IL-2R) increased in the lamina propria. Other
      immunocytes, such as B and T lymphocytes, dendritic cells, and human leukocyte
      antigen DR-1 (HLADR)-positive cells, did not exhibit a significant increase in
      the inflamed ileum compared with the normal proximal jejunum. We conclude that
      stimulation of GMCs may be the major motility marker of intestinal inflammation.

PMID- 8572224
TI  - Regulation of lineage-specific transcription of the sucrase-isomaltase gene in
      transgenic mice and cell lines.
AB  - Sucrase-isomaltase (SI), a gene expressed exclusively in absorptive enterocytes,
      was used to examine the molecular mechanisms that regulate cell-specific gene
      expression in the intestinal epithelium. Transgenic mice were made with a
      construct containing nucleotides -8,500 to +54 of the mouse SI gene linked to a
      human growth hormone reporter gene. In adult transgenic animals, high-level
      transgene expression was limited to the small intestine, with low levels of
      ectopic expression in the colon. In contrast to the endogenous gene that is
      expressed only in enterocytes, the transgene was expressed in all four cell
      lineages, including enterocytes, enteroendocrine, goblet, and Paneth cells. To
      examine this process of lineage-specific expression further we studied Caco-2 and
      COLO DM cell lines, which model enterocytes and enteroendocrine cells,
      respectively. Reminiscent of results in transgenic animals, only Caco-2 cells
      transcribed the endogenous SI gene, whereas both Caco-2 and COLO DM cells
      supported transcription from chimeric SI reporter gene constructs. Taken
      together, these data suggest that each intestinal cell lineage has the cellular
      machinery to transcribe the SI gene. Moreover, these findings imply that
      transcription is normally repressed in nonenterocytic cells, possibly via a
      transcriptional silencer residing outside of the region of the SI gene examined
      in these studies.

PMID- 8572225
TI  - Effect on muscarinic acetylcholine receptors after experimental neuronal ablation
      in rat colon.
AB  - The etiology of denervation hypersensitivity was studied using a rat model.
      Degeneration of the myenteric plexus was produced by direct application of 0.1%
      benzalkonium chloride to the serosal surface of the distal colon. Thirty days
      later, the treated group was compared with a control group undergoing a sham
      operation. The treated group showed that the decreased number of ganglion cells
      of the myenteric plexus on routine stain and acetylcholinesterase staining
      demonstrated the myenteric plexus in the treated group diminished
      acetylcholinesterase activity. Methacholine (1%), a muscarinic agonist, increased
      intraluminal pressure in treated but not control rats. The dose-response curve of
      colonic muscle strips to oxotremorine showed a shift to the left, indicating
      greater sensitivity, in the treated bowel, with a 50% effective dose (ED50) of
      2.5 x 10(-8) in treated muscle and 2.2 x 10(-7) in controls. Binding studies
      using [3H]quinuclidinyl benzilate ([3H]QNB) showed that the specific maximal
      binding (Bmax) for [3H]QNB was greater in treated than in untreated animals (228
      +/- 26.1 and 135 +/- 42.9 fmol/mg protein, respectively; P < 0.01), even though
      the dissociation constants (Kd) were the same (0.398 +/- 0.083 and 0.406 +/-
      0.065). These findings show that acquired denervation hypersensitivity in this
      model is due to an increase in the number of muscarinic acetylcholine receptors.

PMID- 8572226
TI  - PYY and GLP-1 contribute to feedback inhibition from the canine ileum and colon.
AB  - To explore mechanisms whereby unabsorbed nutrients in the ileum inhibit the upper
      gut ("ileal brake"), we perfused the canine ileum or colon and monitored phase 3
      in the duodenum. Fasting motility was recorded when the ileum or colon was
      perfused with 154 mM NaCl, a mixed isotonic nutrient solution (Ensure), or
      individual nutrients (maltose, casein hydrolysates, or sodium oleate). Blood
      samples were collected before and during the perfusions. The ileum was also
      perfused with 154 mM NaCl while peptide YY (PYY) was infused by vein. In both
      sets of experiments, plasma levels of PYY, neurotensin, and glucagon-like peptide
      1 (GLP-1) were measured. Ileal or colonic perfusion of Ensure delayed phase 3
      [migrating motor complexes (MMC)] in the duodenum, inhibited ileal motility, and
      increased plasma levels of PYY and GLP-1. Ileal casein and oleate and colonic
      casein also delayed the duodenal MMC. The MMC cycle length and plasma levels of
      PYY were closely correlated. Intravenous PYY prolonged the MMC cycle; an
      intravenous dose of 100 pmol.kg-1.h-1 of PYY mimicked the effects of ileal
      Ensure. These results support the hypothesis that PYY, and possibly GLP-1,
      participate in the ileal brake. This negative feedback loop also affects the
      distal small bowel. The proximal colon also triggers the feedback inhibition of
      gut motility (colonic brake).

PMID- 8572227
TI  - Tumor necrosis factor-alpha inhibits lipid and lipoprotein transport by Caco-2
      cells.
AB  - Cytokines, important mediators of inflammation, have been shown to cause
      disturbances in circulating and hepatic lipid metabolism. Although the intestine
      plays a major role in dietary fat transport and largely contributes to plasma
      lipoproteins, the effects of cytokines on intestinal lipid handling remain
      unknown. In the present study, the modulation of lipid, apoprotein, and
      lipoprotein synthesis and secretion by tumor necrosis factor-alpha (TNF-alpha)
      was investigated in Caco-2 cells. Highly differentiated and polarized cells (20
      days in culture) were incubated for 20 h with recombinant human TNF-alpha (100
      500 ng/ml). No cytotoxic effect of TNF-alpha cells was observed, as indicated by
      the determinations of Caco-2 cell viability and monolayer transepithelial
      resistance. Moreover, no differences in cell maturation (sucrase activity) or
      cell proliferation ([3H]thymidine incorporation and cell cycle analysis) were
      detected between treated and control cultures. Significant inhibition of lipid
      secretion by TNF-alpha was observed, with the greatest reduction at 500 ng/ml.
      TNF-alpha significantly decreased Caco-2 cell secretion of phospholipids (22%),
      triglycerides (30%), and cholesteryl ester (37%). It also significantly
      diminished the export of newly synthesized low-density lipoproteins (LDL; 20%)
      and high-density lipoproteins (HDL; 13%), with a lesser effect on very low
      density lipoproteins (VLDL; 3%). The lipid composition of these lipoproteins was
      minimally affected. De novo synthesis of apo A-I, apo B-100, and apo B-48 was
      also markedly reduced by TNF-alpha. Sphingomyelinase activity was not increased
      and cell content of sphingomyelin was not altered, suggesting that inhibitory
      effects on lipid and apoprotein of TNF-alpha were not mediated by the ceramide
      pathway. Our results indicate that TNF-alpha may play a role in modulating
      intestinal lipid metabolism, thus affecting circulating lipoproteins.

PMID- 8572228
TI  - Posttranscriptional regulation of mRNA levels in rat liver associated with
      deoxycholic acid feeding.
AB  - We investigated the effects of bile acid feeding on the mRNA levels and
      transcriptional activity of genes involved in various facets of hepatic cell
      function. Rats were maintained for 10 days on standard diet supplemented with
      combinations of 1 and 0.4% deoxycholic acid and ursodeoxycholic acid. Significant
      reductions in mRNA levels for liver fatty acid binding protein, albumin, the
      asialoglycoprotein receptor, connexins 32 and 26, and cytochromes P-450IIB1 and P
      450IIE1 were associated with 1% deoxycholic acid feeding. Conversely, the 1%
      deoxycholic acid-fed animals exhibited increased mRNA levels for cholesterol 7
      alpha-hydroxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, multidrug
      resistance, procollagens, extracellular matrix, protooncogenes, tumor
      suppressors, and cyclins. The 0.4% deoxycholic acid-fed animals exhibited
      increased mRNA levels for c-jun, H-ras, p53, cyclins D1 and D3, fibronectin, and
      procollagens alpha 1(I) and alpha 1(III). Transcriptional rate changes could not
      account for the observed changes in steady-state mRNA levels. Ursodeoxycholic
      acid feeding had no significant effect on gene expression and almost completely
      inhibited the changes associated with 1% deoxycholic acid when coadministered.
      The results indicate that dietary ingestion of deoxycholic acid profoundly
      affects hepatic gene expression in the rat, and regulation occurs primarily at
      the posttranscriptional level.

PMID- 8572229
TI  - Resection-induced colonic adaptation is augmented by IGF-I and associated with
      upregulation of colonic IGF-I mRNA.
AB  - The effects of exogenous insulin-like growth factor-I (IGF-I) on colonic
      adaptation were examined in male Sprague-Dawley rats (n = 60, 225-275 mg) after
      either a 60% small bowel and cecal resection (RX) or mid-small bowel transection
      with reanastomosis (TX). Animals received a 7-day treatment with either IGF-I
      (2.4 mg.kg-1.day-1) or vehicle (V; 0.1 mol/l acetic acid). Body weight decreased
      significantly after resection (-25.6 +/- 4.0 g; P < 0.05 vs. TX/V). IGF-I
      treatment significantly reduced weight loss after resection (-12.4 +/- 3.8 g; P <
      0.01 vs. RX/V) and induced significant weight gain after transection (15.6 +/-
      4.0 g; P < 0.05 vs. TX/V). Plasma IGF-I decreased with resection (526 +/- 41 TX/V
      vs. 344 +/- 17 ng/ml RX/V; P < 0.01). IGF-I treatment significantly increased
      plasma IGF-I levels (805 +/- 100 ng/ml TX/IGF, 677 +/- 56 ng/ml RX/IGF). After
      resection, IGF-I treatment significantly increased colonic mucosal weight, DNA,
      protein content, and crypt depth when compared with resection alone (P < 0.05).
      Colonic water absorption, measured by an in vivo [3H]polyethylene glycol assay,
      was significantly increased by IGF-I treatment in resected animals (399 +/- 23
      RX/IGF vs. 306 +/- 32 microliter.cm-1.h-1 RX/V; P < 0.05). Resection resulted in
      increased steady-state colonic IGF-I mRNA (182% of TX/V; P < 0.01) without
      significantly affecting IGF-I receptor mRNA expression. Regulation of IGF binding
      protein (BP)-3 and -4 was discoordinate, with IGFBP-3 mRNA tending to decrease
      with resection (67% of TX/V; P is not significant) and IGFBP-4 increasing
      significantly (191% of TX/V; P < 0.05). An important role for IGF-I in colonic
      adaptation after massive intestinal resection is indicated by 1) significantly
      enhanced colonic mucosal growth and water absorption with IGF-I treatment and 2)
      postresection upregulation of colonic IGF-I mRNA and alteration of IGFBP-3 and
      IGFBP-4 mRNA expression.

PMID- 8572230
TI  - Human recombinant interleukin-1 beta inhibits nicotinic transmission in neurons
      of guinea pig pelvic plexus ganglia.
AB  - The actions of human recombinant interleukin-1 beta (hrIL-1 beta) were tested on
      guinea pig pelvic plexus ganglion neurons using intracellular
      electrophysiological methods in vitro. hrIL-1 beta caused membrane depolarization
      associated with a decreased input resistance or inward currents in 54% of neurons
      tested. hrIL-1 beta caused a hyperpolarization associated with an increase in
      input resistance or outward currents in 30% of neurons tested. hrIL-1 beta-evoked
      responses were not altered by hexamethonium (100 microM), atropine (0.5 microM),
      yohimbine (0.3 microM), or naloxone (1 microM), indicating that cholinergic,
      alpha 2-adrenergic, or opioid receptors were not involved. Drugs that inhibit
      Na+, Ca2+, or K+ channels did not change hrIL-1 beta-evoked responses.
      Stimulation of synaptic inputs to pelvic ganglion neurons evoked nicotinic
      cholinergic fast excitatory postsynaptic potentials (fEPSPs). hrIL-1 beta
      inhibited fEPSPs in 44% of neurons tested but had no effect on acetylcholine
      induced depolarizations. An IL-1 beta receptor antagonist blocked all actions of
      hrIL-1 beta. In summary, hrIL-1 beta has excitatory and inhibitory actions on
      pelvic ganglion neurons. Inhibition of fEPSPs by hrIL-1 beta may be due to
      presynaptic inhibition of acetylcholine release.

PMID- 8572231
TI  - Bile salt-dependent inhibition of gallbladder emptying.
AB  - Little is known about the inhibitory controls of gallbladder emptying. Since
      cholestyramine, a binding agent that reduces luminal concentration of bile salt,
      has been reported to accelerate gallbladder emptying, suggesting that bile salt
      is inhibitory, we hypothesized that fat-stimulated gallbladder emptying is
      inhibited by a bile salt-dependent mechanism. To test this idea, we compared
      gallbladder emptying in 10 dogs equipped with duodenal and jejunal fistulas that
      allowed for complete diversion of the native bile while varying concentrations of
      bile salt were perfused into the small intestine. In six dogs, 30 mM oleate and
      5, 10, or 20 mM sodium taurocholate was perfused into the whole intestine. Since
      bile salt availability alters fat absorption, in a separate experiment in seven
      dogs we also compared gallbladder emptying while 30 mM oleate and 5 mM
      taurocholate were perfused between fistula and 0, 5, 10, or 20 mM taurocholate
      were perfused beyond jejunal fistula to separate fat from varying concentrations
      of bile salt. We found that intestinal taurocholate inhibited fat-stimulated
      gallbladder emptying in a dose-dependent fashion (P < 0.01; analysis of variance,
      significant linear dose effect) and that the inhibitory effect of bile salt
      persisted when 5-20 mM taurocholate was perfused beyond the jejunal fistula (0
      vs. average of 5-20 mM taurocholate, P < 0.05, paired t-test). We conclude that
      fat-stimulated gallbladder emptying is inhibited by a bile salt-dependent
      inhibitory mechanism.

PMID- 8572232
TI  - Barrier function of the gastric mucus gel.
AB  - The gastric epithelium is covered by a continuous layer of secreted mucus and
      bicarbonate. The function of this mucobicarbonate layer in terms of protecting
      the epithelial cells from luminal acid is controversial. Several studies
      conducted in vitro have shown that gastric mucus can slow proton diffusion and
      can enable the formation of a pH gradient across the mucobicarbonate layer. In
      our laboratory, simultaneous measurements of intracellular pH and the thickness
      of the mucus gel overlying gastric surface cells in vivo indicated that surface
      cell acidification rates and mucus gel thickness were inversely related. This
      suggests that the gastric mucobicarbonate layer delays proton permeation into
      gastric surface cells, enabling secreted bicarbonate to neutralize luminal acid.
      Several theoretical models, including the effects of mucus and bicarbonate
      secretion, convection, stirring, and lipids are offered as a possible explanation
      for the experimental observations. Lipid content and additional unstirred layers
      outside of the mucus gel are offered as possible explanations for the
      experimental observations. On the basis of the available data and theoretical
      considerations, we can conclude that all of these factors probably interact in an
      integrated manner to protect the gastric epithelial cells from damage due to
      luminal acid.

PMID- 8572233
TI  - Differential regulation of the mannose and SP-A receptors on macrophages.
AB  - Two carbohydrate-dependent mechanisms exist on alveolar macrophages to clear
      mannose-containing pathogens: receptor-mediated entry of non-opsonized
      microorganisms via the mannose receptor and receptor recognition of pathogens
      opsonized with surfactant-associated protein A (SP-A). A number of studies have
      demonstrated that mannose receptor expression is tightly linked to the functional
      state of the macrophage. In the present study, we investigated regulation of
      binding of SP-A to its receptor on macrophages by the same agents that regulate
      mannose-receptor expression. Phorbol 12-myristate 13-acetate, lipopolysaccharide
      (LPS), and interferon-gamma treatment of rat marrow-derived macrophages increased
      SP-A binding by 163, 296, and 337%, respectively, over untreated controls.
      Mannose-receptor activity was reduced to 75, 60, and 25% of control levels by
      these agents. Dexamethasone increased mannose receptor activity to 225%, while
      decreasing SP-A binding to 44% of controls. Addition of granulocyte macrophage
      colony stimulating factor (GM-CSF) to human monocytes on day 0 dramatically
      increased mannose-receptor activity on day 5 over the non-serum control. SP-A
      binding was highest to freshly isolated monocytes and decreased to < 10% after
      differentiation in the presence of GM-CSF. After intraperitoneal injection of
      dexamethasone, rat alveolar macrophages isolated at 24 h expressed increased
      mannose-receptor activity and decreased SP-A binding. LPS injection resulted in
      increased SP-A binding and decreased mannose-receptor activity. In every
      instance, SP-A binding was inversely regulated with respect to mannose-receptor
      expression. We therefore speculate that the mannose receptor is a first-line host
      defense receptor that is turned off during inflammation. SP-A in the alveolar
      space can then act as a lung-specific opsonin and mediate clearance of pathogens
      via the upregulated SP-A receptor.

PMID- 8572234
TI  - Posttranslational processing of surfactant protein C in rat type II cells.
AB  - Pulmonary surfactant consists of phospholipids and proteins that form a stable
      monolayer at the surface of the alveoli to prevent lung collapse. Surfactant
      protein C (SP-C) is a hydrophobic 4-kDa palmitoylated protein derived from a 21
      kDa precursor. We determined the membrane insertion, proteolytic processing, and
      subcellular location of 21-kDa proSP-C. In vitro, proSP-C associated with canine
      microsomes, and the NH2-terminal of proSP-C was protected from digestion with
      proteinase K, suggesting that proSP-C was inserted in a type III transmembrane
      configuration. Treatment of freshly isolated rat type II cells with cerulenin
      blocked acylation of the 21-kDa precursor. Pulse-chase labeling of type II cells
      demonstrated proSP-C processing intermediates of 19, 16, and 13 kDa that
      contained the NH2-terminal of proSP-C. Proteolytic processing of proSP-C was
      inhibited by incubation at 20 degrees C, suggesting that processing of proSP-C
      begins in a late Golgi or post-Golgi compartment. Immunogold labeling of rat lung
      with an antiserum to the NH2-terminal of proSP-C identified proSP-C in the trans
      Golgi and multivesicular bodies but not in lamellar bodies. These findings
      suggest that proSP-C processing takes place in the trans-Golgi and multivesicular
      bodies before SP-C is incorporated into lamellar bodies.

PMID- 8572235
TI  - Ozone exposure of human tracheal epithelial cells inactivates cyclooxygenase and
      increases 15-HETE production.
AB  - We assessed the immediate and prolonged effects of ozone on arachidonic acid (AA)
      metabolism by primary cultured human tracheal epithelial (TE) cells. TE
      monolayers were exposed at a gas-fluid interface to air or 0.1, 0.25, or 0.5 ppm
      ozone (15 min air, then 45 min air/ozone), and serially collected effluents were
      analyzed by thin-layer chromatography (TLC) and/or high-performance liquid
      chromatography. Release of prostaglandin E2 (PGE2) and AA, but not 15
      hydroxyeicosatetraenoic acid (15-HETE) or its metabolites, was detected from
      cultures prelabeled with [14C]AA. PGE2 production, measured by immunoassay, was
      nearly constant during air exposure. In contrast, PGE2 increased two- to
      threefold during the first 15-min exposure to all concentrations of ozone, but
      then progressively declined to 78 +/- 17, 57 +/- 12 (P < or = 0.05), and 45 +/-
      15% (P < or = 0.05) of air controls after exposure to 0.1, 0.25, and 0.5 ppm
      ozone. Ozone did not induce a new spectrum of AA metabolites; only PGE2, lesser
      amounts of PGF2 alpha, and 15-HETE were present in media and cell extracts of air
      or ozone-exposed cultures provided with 30 microM exogenous AA. However,
      cyclooxygenase (CO) activity (PGE2 produced from 30 microM AA) decreased to 82 +/
      9, 53 +/- 8 (P < or = 0.05), and 28 +/- 6% (P < or = 0.05) vs. controls after
      0.1, 0.25, and 0.5 ppm ozone, whereas 15-HETE production was unimpaired. When
      cells exposed to 0.5 ppm ozone were maintained for up to 6 h in 5% CO2-air,
      spontaneous PGE2 production remained decreased and recovery of CO activity was
      extremely slow. TLC analysis of lipid extracts from [14C]AA-labeled cells
      revealed a nearly twofold increase in free intracellular 15-HETE, and hydrolysis
      of phospholipids demonstrated increased esterified 15-HETE. Exposure of human TE
      cells to ozone leads to a transient increase followed by prolonged decrease in
      PGE2 production and increased intracellular retention of 15-HETE. Loss of the
      bronchodilator and anti-inflammatory properties of epithelial PGE2, with or
      without increased 15-HETE, might contribute to ozone-induced airway dysfunction.

PMID- 8572236
TI  - Synthesis and processing of hydrophobic surfactant protein C by isolated rat type
      II cells.
AB  - Surfactant protein C (SP-C) is a 3.7-kDa hydrophobic peptide isolated from
      organic extracts of pulmonary surfactant which is secreted by alveolar type II
      cells after synthesis and posttranslational processing of a 21-kDa proSP-C
      peptide (SP-C21). Previously characterized epitope-specific proSP-C antisera were
      used to study early proteolytic steps of proSP-C processing by adult rat type II
      cells. Western blotting and immunocytochemistry using anti-NPROSP-C (epitope =
      Met10-Glu23) each demonstrated marked attenuation of proSP-C protein expression
      by culture on plastic. Processing was therefore studied by metabolic labeling of
      freshly isolated type II cells maintained in suspension in serum-free media. With
      the use of anti-NPROSP-C, immunoprecipitation of cell lysates continuously
      labeled for 4 h with [35S]methionine demonstrated radiolabeled bands of M(r) 21,
      16, and 10-6,000 while anti-CTERMSP-C (epitope = Ser149-Ser166) failed to detect
      35S-bands of M(r) < 16,000. Pulse-chase studies demonstrated synthesis of 35S
      proSP-C21 with a time-dependent dependent appearance of 16-kDa and 10- to 6-kDa
      forms which was blocked by addition of brefeldin A. SP-C precursors were not
      detected in the media. Quantitative analysis of the major bands by direct beta
      counting indicated a precursor-product relationship between SP-C21 and SP-C16.
      These results demonstrate the utility of freshly isolated type II cells for
      characterization of SP-C synthetic pathways and show that early proSP-C
      processing events include synthesis of a 21-kDa primary translation product
      followed by extensive intracellular proteolysis of the proSP-C COOH-terminal in
      subcellular compartments of type II cells which are distal to the trans-Golgi
      network.

PMID- 8572237
TI  - Composition of extracellular matrix of type II pulmonary epithelial cells in
      primary culture.
AB  - Type II pulmonary epithelial cells in primary culture synthesize and deposit an
      extracellular matrix which has reciprocal biological effects on cellular
      differentiation. The present work establishes conditions for metabolic labeling
      of matrix constituents and for separation of cells from the associated matrix; it
      also defines matrix composition, which does not appear to change qualitatively
      between days 2 and 6 of primary culture. Type II cells synthesize and deposit a
      spectrum of radiolabeled components on the culture surface. These include
      fibronectin, laminin, type IV collagen, and plasminogen activator inhibitor-1,
      along with additional unidentified proteins. Few radiolabeled proteins in medium
      conditioned by type II cells bind nonspecifically to the culture surface in the
      absence of cells. Fibroblasts and macrophages, which may contaminate the primary
      cultures, do not appear to contribute substantially to the type II cell matrix.
      These results demonstrate that type II cells synthesize and deposit a complex
      multicomponent extracellular matrix. The work provides a basis for further
      investigations of bidirectional interactions between type II cells and the
      extracellular matrix.

PMID- 8572238
TI  - Turnover of fibronectin and laminin by alveolar epithelial cells.
AB  - Type II pulmonary epithelial cells in primary culture synthesize and assemble a
      multicomponent extracellular matrix which exhibits biological activity in vitro.
      Simultaneously, the pneumocytes degrade components of the underlying matrix, such
      that matrix composition may be determined by the balance of synthesis and
      turnover. The present work defines turnover of the specific matrix glycoproteins,
      fibronectin and laminin, both in the type II cell and in its extracellular
      matrix. Pulse-chase experiments demonstrate that both fibronectin and laminin,
      identified by immunoprecipitation, turn over rapidly in the cell and
      extracellular matrix compartments, with half-lives < 10 h. In the cell
      compartment, initial rates of laminin turnover are more rapid than those of
      fibronectin on culture day 2, but these rates are similar on day 6. Matrix
      fibronectin also turns over rapidly, with similar rates on day 2 and day 6.
      During the chase interval, small but increasing amounts of immunoprecipitable
      fibronectin are detected in the medium, suggesting that a portion of the
      glycoprotein may be released to the extracellular compartment, rather than
      degraded. Alternatively, release of immunoreactive glycoprotein may involve
      ongoing processing and secretion of residual radiolabeled fibronectin by the
      cells. The results suggest that matrix composition may be determined by turnover,
      as well as synthesis, of its components.

PMID- 8572239
TI  - Cholinergic regulation of voltage-dependent Ca2+ channels in porcine tracheal
      smooth muscle cells.
AB  - To investigate cholinergic regulation of voltage-dependent Ca2+ channels (VDCs)
      in airway smooth muscle, we measured inward currents through VDCs in
      enzymatically dispersed porcine tracheal smooth muscle cells using conventional
      (10 mM Ca2+ as charge carrier) and nystatin-perforated (5 mM Ba2+ as charge
      carrier) whole cell patch clamp techniques. Carbachol (CCh) had significant and
      dose-dependent inhibitory effects on inward currents (12% with 10(-7) M and 42%
      with 10(-6) M) in perforated whole cell clamp experiments, but had no effect on
      currents in conventional whole cell experiments. CCh also shifted the steady
      state inactivation curve to more negative potentials. Further experiments tested
      the hypothesis that CCh inhibits VDCs in part by the activation of protein kinase
      C (PKC). Phorbol 12,13-diacetate, an exogenous PKC activator, inhibited currents
      through VDCs. and calphostin C, a specific PKC inhibitor, antagonized the
      inhibitory effect of CCh. Furthermore, intracellular exposure to the activating
      PKC fragment 530-558, using a pipette perfusion technique, also inhibited
      currents through VDCs. We conclude that cholinergic receptor stimulation can
      inhibit inward Ca2+ currents through VDCs of porcine tracheal smooth muscle and
      that this effect may be mediated in part by activation of PKC.

PMID- 8572240
TI  - Role of muscarinic M2 receptors in regulating beta-adrenergic responsiveness in
      maturing rabbit airway smooth muscle.
AB  - Muscarinic M2 and M3 receptor subtypes have been pharmacologically distinguished
      in airway smooth muscle. Whereas M3 receptors have been associated with smooth
      muscle contraction, M2 receptors have been implicated in Gi protein-coupled
      inhibition of adenylyl cyclase. To determine whether the role of M2 receptors
      varies with age in tracheal smooth muscle (TSM), dose-dependent relaxation
      responses to isoproterenol were compared in TSM isolated from 3-day-old and adult
      rabbits precontracted with acetylcholine (ACh) in the absence (control) and
      presence of an M2 receptor antagonist (gallamine or methoctramine). From
      sustained half-maximal ACh contractions, adult TSM were 5.6-fold less sensitive
      than 3-day-old tissues to isoproterenol-induced relaxation. Furthermore, the
      magnitude of muscarinic functional antagonism of isoproterenol-mediated TSM
      relaxation, assessed by varying the initial degree of ACh-induced contraction,
      significantly increased with age. In gallamine- and methoctramine-treated
      tissues, the relaxation-response curves to isoproterenol were shifted to the left
      in both 3-day-old and adult TSM. In contrast, pretreatment with either M2
      receptor antagonist had no significant effect on the magnitude of muscarinic
      functional antagonism at either age. Moreover, Western blot analysis of G alpha i
      common and specific subunit expression in TSM membranes demonstrated
      qualitatively similar levels in 3-day-old and adult TSM. Collectively, these
      findings provide new evidence that 1) there exist inherent age-dependent
      differences in both the airway relaxant responsiveness to beta-adrenoceptor
      stimulation and muscarinic functional antagonism of beta-adrenergic relaxation,
      and 2) the latter are attributed to mechanisms other than ontogenetic alteration
      in M2 receptor function or Gi protein expression in maturing rabbit TSM.

PMID- 8572241
TI  - Plasticity of airway cell proliferation and gene expression after acute
      naphthalene injury.
AB  - The goal of this study was to determine the temporal and spatial sequence of
      events that accompany lung injury and repair after parenteral administration of
      the Clara cell-specific cytotoxicant, naphthalene. Changes in airway epithelial
      cells were evaluated by measuring alterations in the expression of markers for
      differentiated Clara cells (CYPIIF and Clara cell 10-kDa secretory protein,
      CC10), distal airway/alveolar type II cells (surfactant protein B; SP-B) and for
      cycling/proliferating cells (cyclin dependent kinase 1;CDK1). Naphthalene-induced
      Clara cell cytotoxicity resulted in the exfoliation of epithelial cells
      containing CC10 protein. This was accompanied by a dramatic reduction in the
      abundance of mRNA for CC10 and CYPIIF. Large numbers of CDK1 mRNA-positive cells
      were identified in and around bronchioles and terminal bronchioles 48 h after
      treatment. This cellular proliferation resulted in the population of airways by
      immature epithelial cells lacking normal levels of CC10 mRNA but overexpressing
      SP-B mRNA. Seventy-two hours after naphthalene treatment a reduction in CDK1 mRNA
      positive cells was noted within bronchioles and terminal bronchioles at all
      locations, with the exception of airway bifurcations. At airway bifurcations CDK1
      mRNA appeared to be more abundant at the 72-h time point than at 48 h. Comparison
      of these sections with serial sections probed for CC10 mRNA demonstrated a
      correlation between the expression of CDK1 and CC10 mRNA at bifurcations.
      Temporal increases in the abundance of CC10 mRNA observed at later time points
      were largely accounted for by the processive maturation of newly repopulated
      cells neighboring bifurcations in bronchioles. These studies identify spatially
      distinct populations of cells that act in concert to repopulate naphthalene
      injured airways and support the notion that branch point cells play an important
      role in the maturation of newly regenerated airway epithelial cells after acute
      injury.

PMID- 8572242
TI  - Cellular response in naphthalene-induced Clara cell injury and bronchiolar
      epithelial repair in mice.
AB  - Clara cells, progenitors for bronchiolar epithelium, are also primary targets for
      metabolically activated pulmonary cytotoxicants and have an abundance of the
      cytochrome P-450 monooxygenases required for xenobiotic metabolism. To define the
      repair pattern after massive Clara cell injury, mice were treated with
      naphthalene, and lungs evaluated 1-14 days postinjury (DPI). Clara cells of
      terminal bronchioles were vacuolated and swollen 1 DPI, exfoliated 2 DPI, and
      resembled controls at 14 DPI. The volume fraction of vacuolated cells was highest
      1 and 2 DPI and minimal at 5-7 DPI. The volume fraction of normal nonciliated
      cells decreased 40% at 1 DPI. Cell proliferation increased within epithelium and
      interstitium at 1 DPI, was maximal at 2 DPI, and at all other time points was
      similar to baseline levels. Expression of Clara cell differentiation markers was
      barely detectable in terminal bronchiolar epithelium at 1 and 2 DPI, clearly
      detectable at 4 DPI, and gradually returned to control levels at 5-14 DPI. We
      conclude that bronchiolar epithelial repair after naphthalene injury involves
      distinct phases of proliferation and differentiation, proliferation of cells that
      are not differentiated Clara cells, and interaction of multiple cell types
      including nontarget cells.

PMID- 8572243
TI  - Fibroblasts isolated after fibrotic lung injury induce apoptosis of alveolar
      epithelial cells in vitro.
AB  - Primary lung fibroblasts were isolated from patients with idiopathic pulmonary
      fibrosis (HIPF), from normal human lung tissue (NH), from rats treated with 75%
      oxygen and paraquat (PA), and from normal adult rats (NR). Serum-free media
      conditioned by each fibroblast strain were tested on the human A549 cell line
      (HIPF and NH media) or on primary alveolar epithelial cells (AEC) isolated from
      normal adult rats (PA or NR media). Over 20-h incubation, HIPF- or PA-conditioned
      media induced DNA fragmentation and significant decreases in total recoverable
      DNA and cell number of A549 or AEC, respectively; NH or NR media had no
      significant effect relative to serum-free unconditioned media. Apoptosis of A549
      and AEC was detected by altered nuclear morphology and was confirmed by terminal
      deoxynucleotidyl transferase-mediated bio-dUTP nick end labeling. The
      endonuclease inhibitors 10 microM aurintricarboxylic acid and 50 microM zinc
      inhibited HIPF-induced apoptosis of A549 cells by 68 and 71%, respectively. Both
      apoptosis and necrosis were induced by HIPF and PA media in a concentration
      dependent manner. These results suggest that altered fibroblasts emerging during
      fibrotic lung injury release a soluble factor(s) capable of inducing cell death
      and net loss of AEC.

PMID- 8572244
TI  - Oxidant-sensitive and phosphorylation-dependent activation of NF-kappa B and AP-1
      in endothelial cells.
AB  - Relatively low concentrations of reactive oxygen cause reversible alterations of
      endothelial cell signal transduction and gene transcription. The hypothesis that
      low levels of oxidant stress activate retention of trans-acting proteins in the
      nucleus was investigated by determining time and dose requirements for oxidant
      stimulated nuclear protein binding to consensus DNA sequences for nuclear factor
      (NF)-kappa B or activator protein 1 (AP-1). Nuclear proteins were extracted from
      low passage porcine aortic endothelial cells 15 min to 24 h after addition of
      increasing concentrations of H2O2. Electrophoretic mobility shift assays
      demonstrated that protein binding to NF-kappa B and AP-1 sequences increases over
      1-2 h after stress relative to time-matched controls and resolves by 24 h. The
      selective protein kinase C inhibitor, calphostin C, prevents approximately 30% of
      this increase. Inhibition of tyrosine kinase activity by herbimycin A (5 microM)
      completely inhibits the response to H2O2. Exposure of intact cells to H2O2
      increases substrate phosphorylation in pp60src immunoprecipitates. The activity
      of pp60src in immunoprecipitates from control cells or of recombinant pp60src
      increases after in vitro addition of H2O2. H2O2-stimulated pp60src activity is
      reduced by pretreatment of the enzyme preparation with N-acetylcysteine. These
      data indicate that oxidants increase nuclear levels of trans-acting factors in
      endothelial cells and that these increases require oxidant-sensitive changes in
      both tyrosine and serine/threonine phosphorylations.

PMID- 8572245
TI  - Differential tachykinin receptor subtype activation in capsaicin and KCl
      contractions of guinea pig trachealis.
AB  - We assessed the role of endogenously secreted tachykinins in mediating
      contraction caused by potassium chloride (KCl) in guinea pig tracheal smooth
      muscle (TSM) strips in vitro. Maximal isometric contraction was elicited with
      approximately 45 mM KCl and was 196 +/- 8% of the response to electrical field
      stimulation (% EFS) in the same tissues. Muscarinic receptor blockade with
      atropine modestly attenuated this contraction caused by KCl to 175 +/- 9 %EFS (P
      < 0.05), and treatment with a selective neurokinin subtype 1 (NK1) receptor
      antagonist, LY-297911, caused even greater inhibition of KCl-elicited contraction
      to 124 +/- 8 %EFS (P < 0.001). By contrast, SR-48968, a selective NK2 antagonist,
      had no effect on contraction caused by KCl (183 +/- 9 %EFS; P = NS vs. KCl
      alone). However, given together at the same concentration, SR-48968 augmented the
      inhibition of contraction caused by LY-297911 to 93 +/- 15 %EFS (P < 0.05 vs. LY
      297911 alone). In contrast to the effect on KCl-induced contraction, LY-297911
      caused only moderate inhibition of the contraction caused by capsaicin to 81 +/-
      13 %EFS (P < 0.05 vs. control, 114 +/- 15 %EFS), whereas SR-48968 caused
      substantial attenuation of contraction caused by capsaicin to 23 +/- 5 %EFS (P <
      0.005 vs. LY-297911). We demonstrate that a significant portion of the
      contraction caused by KCl, in addition to capsaicin, is elicited in guinea pig
      TSM through neurokinin secretion. However, NK1 receptors predominantly mediate
      contraction caused by KCl, and NK2 receptors predominantly mediate contraction
      elicited by capsaicin in guinea pig airway smooth muscle.

PMID- 8572246
TI  - Expression of iNOS in cultured rat pulmonary artery smooth muscle cells is
      inhibited by the heat shock response.
AB  - The heat shock response is a highly conserved stress response known to alter
      patterns of gene expression in many cell types. We hypothesized that interleukin
      1 beta (IL-1 beta)-mediated inducible nitric oxide synthase (iNOS) gene
      expression would be inhibited after induction of the heat shock response in
      cultured rat pulmonary artery smooth muscle cells (RPASMC). Exposure of RPASMC to
      sodium arsenite or heat led to expression of heat shock protein-70 (HSP-70) in a
      time- and concentration-dependent manner. Prior induction of the heat shock
      response inhibited IL-1 beta-mediated iNOS gene expression in a time- and dose
      dependent manner. The inhibitory effects were not due to cytotoxicity, since cell
      viability was not affected by either sodium arsenite, heat, IL-1 beta, or their
      combination. Transcriptional analysis via transient transfection of the murine
      macrophage iNOS promoter [-1592 and -367 base pairs (bp)], upstream from the
      reporter gene luciferase, revealed that the heat shock response did not affect IL
      1 beta-mediated promoter activation, as measured by luciferase activity. We
      conclude that induction of the heat shock response inhibits IL-1 beta-mediated
      iNOS gene expression in cultured RPASMC.

PMID- 8572247
TI  - Lipopolysaccharide upregulates surface expression of CD14 on human alveolar
      macrophages.
AB  - This study was undertaken to examine the surface expression and regulation of
      CD14 on human alveolar macrophages (HAM). HAM obtained by bronchoalveolar lavage
      were cultured with or without LPS and with or without fetal bovine serum (FBS) on
      plastic or Teflon surfaces. CD14 expression was assessed by immunofluorescence.
      The roles of protein tyrosine kinase, protein kinase A, and protein kinase C were
      also evaluated utilizing inhibitors of these enzymes. HAM expressed very low
      levels of surface CD14 at baseline. CD14 was upregulated on HAM with time in
      culture in the presence of FBS and/or LPS; adherence did not affect CD14
      expression. Inhibitors of protein kinase C and protein tyrosine kinase prevented
      the upregulation of CD14 by LPS but did not effect the upregulation of CD14 by
      FBS. These studies show that LPS can upregulate expression of its receptor on HAM
      and that this effect is accentuated by serum-derived factors.

PMID- 8572249
TI  - Respiratory syncytial virus increases IL-8 gene expression and protein release in
      A549 cells.
AB  - The mechanism of respiratory syncytial virus (RSV)-induced inflammation in the
      airways of infants and children is not fully understood. We hypothesized that RSV
      directly induces interleukin (IL)-8 gene expression in airway epithelial cells,
      independent of IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) production.
      Exposure of A549 cells (an airway epithelial cell line) to RSV resulted in
      increased IL-8 mRNA expression and IL-8 protein release from the cells as early
      as 2 h after treatment. Neither IL-1 beta nor TNF-alpha (mRNA or protein) were
      detected. Viral replication was not necessary for the effects of RSV on IL-8 mRNA
      expression and protein release early in the infectious process. However,
      sustained levels of increased IL-8 production required RSV replication. A dose
      response relationship was observed between the multiplicity of infection and IL-8
      production with both active and nonreplicative RSV at the 2-h time point. Both
      active RSV and nonreplicative RSV increased the transcriptional activity of the
      1.6-kb 5' flanking region of the IL-8 gene. Neither active RSV nor nonreplicative
      RSV increased the stability of the IL-8 mRNA in A549 cells. We conclude that RSV
      increases IL-8 gene expression in A549 cells in a biphasic pattern independent of
      viral replication early (2 h) but dependent on viral replication late (24 h).

PMID- 8572248
TI  - CFTR gene transfer corrects defective glycoconjugate secretion in human CF
      epithelial tracheal cells.
AB  - We demonstrate that in immortalized normal human tracheal epithelial cells (NT-1
      and 56FHTE8o-) 14C-labeled glycoconjugate secretion may be regulated
      independently by agonists of the protein kinase A (PKA) and protein kinase C
      (PKC) signaling pathways. In contrast, in immortalized cystic fibrosis (CF) human
      tracheal epithelial cells (CFT-1 and CFT-2), regulation is defective for agonists
      specific for the PKA but not for the PKC pathway. To characterize the involvement
      of the cystic fibrosis transmembrane conductance regulator (CFTR) in regulated
      glycoconjugate secretion, we examined the effect of adenovirus-mediated gene
      transfer of CFTR to CF and control cells. Forty-eight hours after infection, at a
      multiplicity of infection of 50 plaque-forming units per cell, high levels of
      CFTR mRNA were detected by reverse transcription-polymerase chain reaction, and
      de novo synthesis of CFTR protein was demonstrated by immunoblotting. Gene
      transfer to CF cells restored defective adenosine 3',5'-cyclic monophosphate
      (cAMP)-dependent secretion not only of chloride but also of glycoconjugates.
      Taken together, these results argue for a role for CFTR in cAMP-mediated
      glycoconjugate secretion.

PMID- 8572250
TI  - Activation of L-type Ca2+ channels after purinoceptor stimulation by ATP in an
      alveolar epithelial cell (L2).
AB  - In the alveolar epithelium, ATP increases the intracellular Ca2+ concentration
      ([Ca2+]i) and stimulates the secretion of surfactant. We investigated the effects
      of extracellular ATP on the membrane potential (Vm), the whole cell current, and
      [Ca2+]i in a cloned rat alveolar epithelial cell line (L2). In microelectrode
      experiments, ATP caused a sustained depolarization of Vm, resulting from the
      activation of cation and Cl- conductances, as revealed by ion replacements. The
      depolarizing phase of the Vm shift was superimposed by Ca(2+)-dependent
      depolarizing spikes. Spikes were also induced by depolarizing Vm with
      charybdotoxin or maitotoxin. Replacement of bath Ca2+ with Ba2+ or Sr2+ also
      evoked repetitive spikes. Ca2+ (Ba2+, Sr2+)-induced spikes were unaffected by
      pretreatment with ionomycin or thapsigargin. They were, however, completely
      abolished by (+)-isradipine (100 nM) and stimulated by BAY K 8644 (100 nM). Whole
      cell L-type Ca2+ (Ba2+, Sr2+) currents were similarly abolished by (+)-isradipine
      and enhanced by BAY K 8644. L-type Ca2+ channels were further confirmed by
      demonstrating high-affinity dihydropyridine receptors stereoselectively labeled
      by (+)-[3H]-isradipine, apparent dissociation constant < 1 nM. In fura 2
      experiments, ATP evoked a transient elevation of [Ca2+]i in the absence of Ca2+
      and a biphasic sustained elevation in the presence of Ca2+, indicating
      intracellular Ca2+ release and Ca2+ entry. The ATP-induced fura 2 signals were
      unaffected by (+)-isradipine. We conclude that in L2 cells, L-type Ca2+ channels
      are activated after purinoceptor stimulation by ATP. The overall [Ca2+]i response
      is, however, mediated by Ca2+ entry through and (+)-isradipine-insensitive
      mechanism and by intracellular Ca2+ release.

PMID- 8572251
TI  - Mob-1 expression in IL-2-induced ARDS: regulation by TNF-alpha.
AB  - We have recently established an animal model of adult respiratory distress
      syndrome (ARDS)-like microvascular lung injury elicited by infusion of human
      interleukin-2 (IL-2). Based on the pronounced, transcriptional upregulation of
      multiple pro-inflammatory mediators in IL-2-induced ARDS, differential display
      was applied to search for potentially novel genes in this paradigm of lung
      injury. Differential display on total lung RNA derived from IL-2-challenged rats
      presented a highly reproducible 3'-UTR fragment profile in which a band
      (approximately 250 bp), termed B1, was strongly induced. B1 cDNA sequence
      exhibited 99.14% homology to the 3'-UTR of mob-1, a recently cloned gene
      belonging to the C-X-C chemokine superfamily. Furthermore, Northern blot analysis
      showed that IL-2-induced pulmonary mob-1 mRNA was expressed at time points before
      the onset of lung injury and suppressed after TNF-alpha inhibition. These data
      imply that lung mob-1 is a novel, highly inducible gene in a clinically relevant
      model of ARDS and, based on its identification as a chemokine, could participate
      in the development of lung injury.

PMID- 8572252
TI  - Effect of singular neurectomy on the caloric response.
AB  - PURPOSE: This study was performed to determine the contribution of the posterior
      semicircular canal to the vestibulo-ocular responses (VOR) from caloric
      stimulation of the labyrinth. MATERIALS AND METHODS: Seven consecutive patients
      with disabling benign paroxysmal positional vertigo, which was treated with
      singular neurectomy, were tested before and after surgery with bithermal
      stimulation of the operated and nonoperated ears. RESULTS: There was a
      significant (P = .0156) decrease in the VOR from stimulation of the operated ear
      following singular neurectomy. The nonoperated ear showed a variety of changes
      that may have resulted from compensatory mechanisms and/or utricular dysfunction.
      CONCLUSIONS: We conclude that the posterior canal together with the lateral and
      superior canals are responsible for the VOR following caloric stimulation of the
      labyrinth.

PMID- 8572253
TI  - Management of recurrent and chronic sinusitis in children.

PMID- 8572254
TI  - Experimental recurrent otitis media induced by Haemophilus influenzae: protection
      and serum antibodies.
AB  - PURPOSE: To study whether acute otitis media caused by encapsulated or
      nontypeable Haemophilus influenzae confers cross-reactive protective immunity in
      an animal model system and to explore the possible involvement of various humoral
      specific antibodies in protection. MATERIALS AND METHODS: Rats were intrabullarly
      challenged with H influenzae type b and two different nontypeable H influenzae
      strains. One month after the initial infection, the animals were rechallenged
      ipsilaterally or contralaterally with either a homologous or heterologous strain,
      and the susceptibility to reinfection was investigated by otomicroscopy. RESULTS:
      The animals challenged and rechallenged with the type b strain were well
      protected ipsilaterally and contralaterally, while the protection after
      homologous rechallenge with a nontypeable strain was partial in the ipsilateral
      ear and very poor in the contralateral ear. Middle ears previously infected with
      a nontypeable strain remained fully susceptible to infections with heterologous
      strains, but there was an indication of cross-protection in the animal groups
      where the first episode of acute otitis media was caused by type b and the second
      by a nontypeable strain. Using the Western blot technique and an enzyme linked
      immunosorbant assay, the serological response to different outer membrane
      proteins, especially protein D, of H influenzae during and after middle ear
      infection were investigated. The serological response from the type b infected
      animals were generally more distinct, while the antibody levels against protein D
      were lower in these groups compared with the groups infected with nontypeable
      strains. CONCLUSIONS: These data indicate that H influenzae type-b-induced
      experimental otitis media results in a better protection than a nontypeable
      induced, and H influenzae b confers a cross protection.

PMID- 8572255
TI  - MUC2 mucin gene expression in the nose and maxillary sinus.
AB  - PURPOSE: The MUC2 gene encodes the core protein of a mucin expressed in the
      intestine and lower airway. The purpose of this study is to examine if the MUC2
      gene is expressed in the nose and maxillary sinus. MATERIALS AND METHODS: A
      Northern blot analysis and reverse transcription-polymerase chain reaction (RT
      PCR) were performed. For the Northern blot analysis, RNAs were extracted from
      maxillary mucosae and nasal polyps of patients with chronic sinusitis and from
      the inferior turbinates of a nasal allergy patient. For RT-PCR, RNAs were
      extracted from 10 patients with chronic sinusitis, 4 patients with allergic
      rhinitis, 2 patients with hypertrophic rhinitis, and 6 volunteers with normal
      nasal mucosa. RESULTS: Hybridization of the Northern blot with SMUC41 (a part of
      MUC2) cDNA probe showed clear bands in 2 of the 3 samples. In RT-PCR, the first
      round of amplification (35 cycles) failed to give any bands, but the additional
      30 cycles with internal primers gave bands in 6 of 22 samples. CONCLUSIONS: These
      results indicate that MUC2 mucin gene is expressed in the nose and paranasal
      sinus. This two-round RT-PCR method will be useful for analysis of MUC2 mucin
      gene expression using relatively small amount of RNA.

PMID- 8572256
TI  - Arachidonic acid metabolites and sinonasal polyposis. I. Possible prognostic
      value.
AB  - PURPOSE: The etiology of sinonasal polyps is sometimes obscure. This study was
      undertaken to evaluate the potential role of arachidonic acid metabolites (AAm)
      on recurrent polyposis. MATERIALS AND METHODS: Tissue production of prostaglandin
      E2 (PGE2), 6-keto-prostaglandin F1-alpha (PGI2), thromboxane A2 (TxA2), and
      leukotriene C4 (LTC4) by nasal mucosa was determined by radioimmunoassay in 27
      patients with sinonasal polyposis (SNp) and in 10 volunteers. RESULTS: The group
      of patients with SNp with the evidence of recurrences in postoperative period
      (Group 1) showed significantly lower PGE2 concentrations than group of patients
      with SNp recurrences (Group 2). The differences in concentrations of PGI2 in
      mentioned groups were insignificant. In comparison with other groups, a group of
      patients who underwent surgery several times for SNp (Group 4) had a higher mean
      TxA2 concentration. The LTC4 concentrations were the highest in groups of
      patients where SNp recurrences were observed. When the incidence of polyposis
      recurrences (within 18 months after surgery) was correlated with the level of
      LTC4 production at the time of surgery, the rate of recurrence was significantly
      higher in patients with increased LTC4 level than in those with normal LTC4
      levels. CONCLUSIONS: LTC4 might have a prognostic value. The possible role of AAm
      in occurrence of SNp is apparent and suggests possible role for medical
      intervention.

PMID- 8572257
TI  - Mitochondrial mutation associated with nonsyndromic deafness.
AB  - PURPOSE: The first mutation associated with nonsyndromic deafness has recently
      been identified in pedigrees with susceptibility to aminoglycoside ototoxicity
      and in a large Arab-Israeli pedigree. The mutation is maternally transmitted, and
      is a nucleotide substitution in the mitochondrial 12S ribosomal RNA gene. A
      different sequence change, in the mitochondrial tRNA(Ser)(UCN)/COI gene, has been
      proposed as a candidate mutation in a Scottish nonsyndromic deafness pedigree. We
      have now identified a family in New Zealand with maternally inherited
      nonsyndromic sensorineural deafness, and the purpose of the current study is to
      identify the molecular basis of deafness in this family. MATERIALS AND METHODS: A
      family tree was established by history and chart review, and audiological and
      clinical data were obtained. Blood was sampled from 10 family members, and
      lymphoblastoid cell lines were established for 4 of them. The DNA of these
      individuals was extracted, and the mitochondrial genome was analyzed by Southern
      blot analysis for gross rearrangements. Subsequently, the entire coding sequence
      of the mitochondrial genome was sequenced, compared to the normal sequence, and
      all sequence variations were analyzed by allele-specific oligonucleotide
      hybridization or restriction enzyme analysis. RESULTS: Several candidate
      mutations were identified, one of them being the nucleotide 7445 A-->G mutation
      in the mitochondrial tRNAser(UCN)/COI gene. This mutation was heteroplasmic and
      identical to the one previously identified in the Scottish pedigree. CONCLUSIONS:
      The finding of the same heteroplasmic mutation in two independent pedigrees with
      the same phenotype and transmission pattern, establishes this sequence change as
      the most likely determinant of the deafness phenotype in these families. This
      implies that nonsyndromic deafness can be caused by mutations in generalized cell
      processes, such as oxidative phosphorylation, rather than in hearing specific
      molecules.

PMID- 8572259
TI  - Second primary malignancies of the head and neck in children.
AB  - Second malignant neoplasms are not uncommon in children, especially following
      multimodality therapy. The incidence of second cancers may approach 12% at 20
      years following the initial cancer. Diligent surveillance is mandatory over a
      patient's lifetime to minimize morbidity and mortality from second malignant
      neoplasms.

PMID- 8572258
TI  - Management options for infantile subglottic hemangioma.

PMID- 8572260
TI  - Resection of a recurrent nasal tumor via Le Fort I osteotomy approach.

PMID- 8572261
TI  - Optic neuritis secondary to sphenoethmoiditis: surgical treatment.

PMID- 8572262
TI  - Atypical mycobacterial adenitis presenting as a parotid abscess.

PMID- 8572263
TI  - Fibrolipoma of the parotid in a child.

PMID- 8572264
TI  - cDNA selection and other approaches in positional cloning.

PMID- 8572265
TI  - DNA probe assay based on exonuclease III digestion of probes hybridized on target
      DNA.
AB  - A quantitative DNA probe assay process has been developed that uses exonuclease
      III. The fluorophore-labeled DNA probe is hybridized with specific sequences of
      the target DNA and then enzymatically digested. As these probe hybridization and
      digestion cycle reactions are repeated at a fixed temperature, digested probes
      (shortened probes) accumulate in the reaction mixture in a manner similar to a
      DNA polymerase chain reaction. Investigation of the digestion characteristics of
      the DNA probe showed that a slight digestion of a free single-stranded probe
      produces a large background signal, which results in low detection sensitivity.
      The digestion of single-stranded DNA probes is caused by double-stranded
      formations in the molecules. This digestion decreases and the double-stranded
      specific digestion increases with increasing reaction temperature. When the
      reaction occurs at 45 degrees C, the association rate of the enzyme on the double
      stranded DNA is 700 times faster than that on single-stranded DNA. This enables
      selective digestion of double-stranded DNA. The detection limit is 9 x 10(-19)
      mol for a M13-phage DNA.

PMID- 8572266
TI  - Effect of cations on the elution of pectic polysaccharides from anion-exchange
      resins.
AB  - Conditions for quantitatively eluting six plant pectic polysaccharides from
      diethylaminoethyl (DEAE)-columns were established. Cations, surprisingly, greatly
      affected the elution of pectic polysaccharides from these anion-exchange columns.
      Quantitative elution of apple pectic acid was achieved when columns of DEAE
      Sephadex A-25 and DEAE-Trisacryl Plus-M were developed with 0.5 M NH4Cl, 0.5 M
      LiCl, or 0.5 M CsCl in buffer. In contrast, up to 1 M NaCl and KCl in buffer only
      eluted 6.3 to 54% of the apple pectic acid from the two types of columns. In each
      case the retained apple pectic acid was eluted basically quantitatively by 0.5 M
      NH4Cl in buffer. The elution of a pectic polysaccharide fraction from Apium
      graveolens (celery), commercial citrus polygalacturonic acid, and two
      polysaccharides isolated from purified cell walls of Lemna minor (duckweed) from
      columns of DEAE-Trisacryl was incomplete when the columns were developed wit 0.5
      M NaCl or 0.5 M KCl in buffer, ranging from 0 to 89%; however, again, the
      retained portion of each sample was eluted quantitatively or almost so from the
      columns with 0.5 M NH4Cl in buffer. One pectic polysaccharide, commercial citrus
      pectin, was eluted equally well and almost quantitatively by 0.5 M NaCl, KCl and
      NH4Cl in buffer. When a pectic polysaccharide fraction from purified cell walls
      of L. minor was applied to a preparative column of DEAE-Trisacryl Plus-M, 99% of
      the sample was eluted by a gradient of 0 to 0.5 M NH4Cl in buffer.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8572267
TI  - Specific isolation of O-linked N-acetylglucosamine glycopeptides from complex
      mixtures.
AB  - Galactosyltransferase and UDP-[3H]galactose are commonly used to identify O
      linked N-acetylglucosamine (O-GlcNAc)-bearing proteins and peptides. In this
      report we show that immobilized Ricinus communis agglutinin I (RCA I)
      specifically binds in vitro galactosylated O-GlcNAc-bearing peptides,
      facilitating their selective isolation from complex mixtures. First, the peptide
      YSDSPSTST was O-GlcNAc glycosylated, galactosylated, and sialylated. Of these
      three glycoforms, only the one with a terminal galactose interacted with the
      lectin. Next, RCA I was used to isolate glycopeptides from the O-GlcNAc-bearing
      basic phosphoprotein (BPP) of human cytomegalovirus. BPP was overexpressed using
      baculovirus, [3H]galactosylated, digested with trypsin, and fractionated on RCA
      I. Peptides that were not galactosylated passed through the column, whereas the
      majority of the radiolabeled glycopeptides interacted weakly with the lectin and
      did not require lactose or elution. These radiolabeled peptides eluted as a broad
      peak with the leading edge being characterized by more hydrophobic glycopeptides
      and the lagging edge by less hydrophobic peptides, suggesting that the
      polypeptide backbone may influence the interaction with the lectin. Lactose was
      required to elute the remaining radiolabeled peptides, suggesting that these
      peptides are multiply glycosylated. The weakly interacting glycopeptides were
      analyzed directly by liquid chromatography/electrospray-mass spectrometry (LC/ES
      MS). Glycopeptides corresponding to both of the major sites of glycosylation of
      BPP were identified. Thus, RCA I greatly facilitates the selective isolation of
      in vitro galactosylated O-GlcNAc glycopeptides from complex mixtures and
      substantially reduces the purification required for subsequent site-mapping by
      gas-phase sequencing and/or LC/ES-MS.

PMID- 8572268
TI  - One-step extraction and concentration of pigments and acyl lipids by sec-butanol
      from in vitro and in vivo samples.
AB  - Photosynthetic pigments and acyl lipids were simultaneously extracted and
      concentrated by sec-butanol. Pigments extracted with sec-butanol were
      indistinguishable from those extracted using acetone as determined by
      quantitative and qualitative HPLC. Use of sec-butanol has several advantages over
      conventional extraction solvents: (1) pigments are extracted directly from
      polyacrylamide gel slices without an elution step; (2) pigments in dilute,
      isolated pigment-protein complexes are extracted and concentrated without first
      concentrating the sample; (3) when necessary, the concentration factor is readily
      increased by addition of water; (4) sec-butanol extracts acyl lipids and vitamin
      K1 as effectively, but much quicker, than chloroform:methanol; (5) sec-butanol
      rapidly extracts and concentrates pigments from thylakoids of all plant species
      tested and even directly from many algal/higher plant cells, facilitating
      analysis of pigment biosynthetic pathways using radioactive substrates; and (6)
      pigments are stable in sec-butanol for several days at room temperature in the
      dark or for many weeks if stored at -20 degrees C in darkness. Finally, sec
      butanol is preferable to ether for concentrating pigments extracted with acetone.

PMID- 8572269
TI  - Inversion formulae for ellipsoid of revolution macromolecular shape functions.
AB  - Explicit relations linking ellipsoid of revolution shape parameters with the
      axial ration (a/b) have been available for a long time. It is not possible to
      directly invert these functions to give a/b as a function of the shape parameter,
      so in the past graphical or tabular interpolation methods have been necessary. By
      the use of simple unconstrained polynomial expansions this restriction is no
      longer necessary. For the two salient hydration-dependent shape functions (P from
      the frictional ratio and v from the intrinsic viscosity) and the four salient
      hydration-independent shape functions (beta and R, both from sedimentation and
      viscosity measurements, and Lambda and Pi from combining viscosity measurements
      with respectively fluorescence depolarization or thermodynamic second virial
      coefficient measurements) the polynomial expansion coefficients (to no more than
      seventh order) are given for the ranges 1.1 < a/b < 2.0, 2 < 2/b < 10, and 10 <
      a/b < 100. The polynomial coefficients give an excellent fit to the real data
      values, except for four uninteresting cases (where the shape function is too
      insensitive for practical use).

PMID- 8572270
TI  - Determination of intracellular trehalose and glycogen in Saccharomyces
      cerevisiae.
AB  - A simple, sensitive and nonlaborious enzyme-based method has been developed for
      determination of both trehalose and glycogen in yeast cells. The method is based
      on extraction of trehalose and glycogen into a 40 mM acetate buffer (pH 4.8) by
      mechanical disintegration of the cells in a bead mill. Subsequently, trehalose
      and glycogen can be hydrolyzed to glucose by the enzymes trehalase and
      amyloglycosidase, respectively. The formed glucose is quantified by a flow
      injection analyzer based on the enzyme glucose oxidase. The method gives results
      comparable to traditional methods but the simplicity of the analysis results in a
      much lower relative standard deviation. The excellent sensitivity of the glucose
      analyzer means that as little as 1 microgram trehalose or glycogen can be
      determined which reduces the required sample volume. This makes the method ideal
      for physiological studies, e.g., of transients in continuous cultures of
      Saccharomyces cerevisiae. In addition, a consistent procedure has been derived
      for pretreatment and storage of samples.

PMID- 8572271
TI  - A filtration-based assay to quantitate granulocyte-macrophage colony-stimulating
      factor binding.
AB  - Filtration-based binding assays have numerous advantages over centrifugation
      based assays, yet they have not been established for many protein ligands due to
      the high nonspecific binding of the protein to the membrane filter. This paper
      describes a vacuum filtration method that permits quantitative evaluation of
      [125I]GM-CSF binding to its receptor on intact cells. The method includes the use
      of glass fiber filters presoaked in a solution of polyvinylpyrrolidone and Tween
      20 to greatly reduce nonspecific binding of the protein ligand. The ratio of
      specific:nonspecific binding observed with this filtration assay was comparable
      to values reported for centrifugation assays. [125I] GM-CSF binding to HL-60
      cells was shown to be time-dependent, saturable, and specific. The estimated Kd
      (70 pM) and Bmax (160 r/cell) were similar to values reported using
      centrifugation assays. This filtration method is much less labor-intensive, has
      greater sample throughput, and allows for a more rapid determination of GM-CSF
      binding compared to the centrifugation-based assay. Although developed to
      quantitate the binding of GM-CSF to its receptor on intact cells, this assay is
      also applicable to other cytokines and can be used with both intact cells and
      isolated plasma membrane preparations.

PMID- 8572272
TI  - The preparation and use of dispersed cells from fat body of Locusta migratoria in
      a filtration plate assay for adipokinetic peptides.
AB  - A method is described for the preparation of metabolically active and hormone
      sensitive dispersed cells from fat body of Locusta migratoria and their
      subsequent use in a filtration plate assay. This assay measures the uptake of
      radiolabelled acetate into the cells, and the use of dispersed cells reduces the
      time and labor involved in preparing dose-response curves to different test
      peptides and increases the precision of the estimate of potency. As a consequence
      of the reduced variability, fewer replicates per dose are required and, when
      operated as a plate assay, up to eight dose-response curves can be constructed
      per plate. The method described here for measuring metabolite uptake into cells
      and thus determining the potencies of adipokinetic hormones could be applied to
      the assay of both catabolic (glucagon-like) and anabolic (insulin-like)
      substances, not only in other insects, but also in mammalian cells. It could be
      used, therefore, as a suitable screening method for novel active compounds.

PMID- 8572273
TI  - An RNA-competitive polymerase chain reaction method for human matrix gamma
      carboxyglutamic acid protein mRNA measurement.

PMID- 8572274
TI  - Semiquantification of polymerase chain reaction product using a bead
      scintillation proximity assay and comparison with the Southern blot method.

PMID- 8572275
TI  - Method for monitoring ultracentrifuge gradients using a high-performance liquid
      chromatographic diode array detector.

PMID- 8572276
TI  - RNA isolation from solid tumor tissue.

PMID- 8572277
TI  - Flat absorbance background for sucrose gradients.

PMID- 8572278
TI  - Deprotection of S-acetamidomethyl cysteine-containing peptides by silver
      trifluoromethanesulfonate avoids the oxidation of methionines.

PMID- 8572279
TI  - Ultraviolet shadowing of proteins in preparative sodium dodecyl sulfate
      polyacrylamide gel electrophoresis.

PMID- 8572280
TI  - Construction of T-vector for direct cloning and expression of cloned genes in
      Escherichia coli.

PMID- 8572281
TI  - Characterization of tubulin-alkaloid interactions by enzyme-linked immunosorbent
      assay.
AB  - An indirect enzyme-linked immunosorbent assay has been developed to characterize
      the interactions of drugs (bisindol alkaloids and colchicine) with immobilized
      tubulin. The binding of polyclonal antibodies raised in rabbits to tubulin
      heterodimers and monoclonal antibodies against the C-terminal regions of alpha-
      and beta-tubulin subunits is tested at various concentrations of the drugs. The
      results of the displacement experiments showed that (i) the monomeric alkaloids
      compete with neither polyclonal nor monoclonal antibodies for tubulin binding;
      (ii) the dimer alkaloids displace the polyclonal but not the monoclonal
      antibodies from tubulin; and (iii) the inhibitory potencies of the bisindol
      alkaloids of different chemical structures are different. A new semisynthetic
      derivative of bisindol alkaloids, KAR-2, was found to be a powerful ligand in
      inhibiting both tubulin polymerization and immunocomplex formation. Colchicine
      did not inhibit binding of the antibodies to the immobilized tubulin. Competitive
      displacement experiments were also designed to test the anti-tubulin activity of
      drugs in solution. The results suggest that while bisindol alkaloids interact
      with tubulin bound on surface or in solution, colchicine binds exhaustively to
      tubulin in solution and enhances the affinity of polyclonal antibodies probably
      via long-distance interactions between the binding domains in tubulin.

PMID- 8572282
TI  - Independent gene targeting by coelectroporation of multiple vectors.

PMID- 8572283
TI  - Screening of cDNA fragments generated by differential RNA display.

PMID- 8572284
TI  - Analysis of the cyanide metabolite 2-aminothiazoline-4-carboxylic acid in urine
      by high-performance liquid chromatography.
AB  - The cyanide metabolite 2-aminothiazoline-4-carboxylic acid (ATC) was converted to
      N-carbamylcysteine and analyzed by high-performance liquid chromatography (HPLC)
      and fluorometric detection. ATC was first separated from interfering substances
      by passing through the cation exchanger AG 50W-X8. Interfering disulfides were
      converted to thiols by reduction of the eluate with thiopropyl-Sepharose 6B. The
      thiols were then absorbed to the organomercurial absorbent p
      acetoxymercurianiline-Sepharose 4B while ATC was obtained in the effluent. ATC
      was then converted to N-carbamylcysteine by ring opening at high temperature in
      an alkaline environment. Derivatization of N-carbamylcysteine was with N-(7
      dimethylamino-4-methyl-3-coumarinyl)maleimide. The imprecision (CV) of the method
      was 3.6% and the analytical recovery was quantitative. The detection limit was
      0.3 microM. ATC in urine was stable for at least 3 months when stored at -196 to
      +20 degrees C. The ATC concentration in urine was below the limit of detection in
      health nonsmokers. The utility of the method was demonstrated by the finding of
      up to 10.5 microM ATC concentrations in urine samples from human subjects in
      Mozambique living on a high dietary intake of cyanide from the cassava root. In a
      metabolic study rats were exposed to acetonitrile in the drinking water. After 4
      weeks very high ATC levels were found in the urine, representative values from
      two rats being 195 and 525 microM, respectively.

PMID- 8572285
TI  - Strategy of measuring bradykinin and kallidin and their concentration in plasma
      and urine.
AB  - Bradykinin (BK) and kallidin (KAL) derivatives containing a Cys residue instead
      of a Ser residue at positions 6 and 7, respectively [BK(Cys6), KAL(Cys7)], were
      synthesized. These derivatives were linked to BSA via the Cys residue by a
      heterobifunctional cross-linker. The coupling product containing a kinin with
      both free N- and C-terminal ends was used as immunogen. We obtained highly
      sensitive and specific antisera, simultaneously directed against both free ends.
      The radioimmunoassay for BK displays a sensitivity of 0.5-60 fmol BK at a
      dilution of 1:80,000 with 125I-BK(Tyr8) as tracer. Des-Arg9-BK, [BK(1-8)],
      displayed the highest cross-reactivity in the amount of 24%. Des-Arg1-BK and
      smaller molecular weight fragments display a cross-reactivity of less than 0.1%.
      The cross-reactivity of the BK antiserum with KAL is approximately 4%. In
      presence of 125I-KAL(Tyr9) the radioimmunoassay for KAL displays a sensitivity of
      2 to 200 fmol KAL to an antiserum dilution of 1:80,000. The cross-reactivity with
      BK is 0.02%. KAL(Hyp4), BK(Hyp3), and des-Arg10-KAL [KAL(1-9)] show a cross
      reactivity of 6.3, 4.9, and 2.4%. All other natural kinin derivatives show a
      cross-reactivity of less than 1%. Both assays were used to measure BK and KAL
      concentrations in blood and urine in humans after extraction and HPLC separation.
      The BK plasma level 1.97 (SD 0.54) pg/ml. The KAL plasma level is 81.0 (SD 14.3)
      pg/ml, indicating that KAL instead of BK is a circulating peptide. In urine, the
      BK level is 16.3 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8572286
TI  - Labeling of influenza virus with alkylamine-modified horseradish peroxidase.
AB  - A procedure for labeling influenza viruses with alkylamine-modified horseradish
      peroxidase (HRP) was developed to study virus receptor specificities in a virus
      overlay assay. Six alkylamine derivatives of HRP were prepared by the periodate
      oxidation method. Human influenza virus A/PR/8/34 (H1N1) was labeled with the
      alkylamine derivatives, and a variety of parameters for labeling were tested in a
      fetuin-immobilized microplate solid-phase assay. The labeling efficiency of
      influenza virus with the derivatives of HRP was affected by the alkyl chain
      length of the derivatives. The most effective derivative for labeling the virus
      being tested was octylamine-modified HRP (octyl-HRP). The labeling profile of
      A/PR/8/34 by octyl(C8H17)-HRP was analyzed b sucrose density gradient
      centrifugation. The labeling had no effect on viral hemagglutinating activity and
      fetuin binding specificity. The specific binding of the HRP-labeled human
      influenza viruses (A/PR/8/34 and B/Lee/40) to glycolipids was demonstrated by a
      virus overlay assay. In this virus-HRP-labeled system, the virions which bound to
      gangliosides developed on a silica gel thin-layer plate were detected simply and
      rapidly.

PMID- 8572287
TI  - Mild chemical deglycosylation of horseradish peroxidase yields a fully active,
      homogeneous enzyme.
AB  - Horseradish peroxidase isoenzyme C (HRP) contains eight N-linked glycans composed
      of Man, Xyl, Fuc, and GlcNAc. These glycans were resistant to enzymatic
      hydrolysis by endoglycosidases peptide-N4-(N-acetyl-beta-glucosaminyl) asparagine
      amidase F, endo-beta-N-acetyl-glucosaminidase H, and endo-beta-N
      acetylglucosaminidase F under conditions where ovalbumin was deglycosylated.
      However, using anhydrous trifluoromethanesulfonic acid (TFMS) in the presence of
      90 mM phenol for 5 min at--10 degrees C, all carbohydrate except GlcNAc was
      removed. Sixty percent of deglycosylated HRP was active after this TFMS
      treatment. Benzhydroxamic acid affinity chromatography separated active and
      inactive deglycosylated HRP. TFMS treatment, however, introduced negative charges
      in all inactive HRP and in about 90% of the active deglycosylated HRP. The nature
      of this modification has not been identified. After ion-exchange chromatography,
      homogeneous and fully active deglycosylated HRP, showing the original pI of 9,
      electronic absorption spectrum, and enzyme kinetics, was obtained, In this
      purified product no amino acid modifications were detected by amino acid
      analysis, partial sequencing, and mass spectrometry of tryptic peptides. The
      deglycosylated product showed greatly reduced solubility in salt solution
      compared to that of authentic HRP.

PMID- 8572288
TI  - Observation of holoprotein molecular ions of several ferredoxins by electrospray
      ionization-mass spectrometry.
AB  - Several ferredoxins containing [4Fe-4S] or [2Fe-2S] active sites have been
      analyzed by electrospray-ionization-mass spectrometry. For these acidic proteins,
      low pH conditions must be implemented in order to ensure strong signals in
      positive-ionization mode. Under such conditions the iron-sulfur active sites were
      lost in most cases. In contrast, the holoproteins were preserved under negative
      ionization mode conditions: they were weakly but sufficiently ionized and
      information about their cofactor content could be obtained. The experimental
      conditions set up here should provide a useful basis for the detailed
      characterization of more complex iron-sulfur proteins.

PMID- 8572289
TI  - Assay methods for nicotinamide mononucleotide adenylyltransferase of wide
      applicability.
AB  - NMN adenylyltransferase (NMNAT) reversibly catalyzes the synthesis of NAD+ or
      NaAD+ from ATP and NMN or NaMN. In this work, we describe a continuous coupled
      spectrophotometric assay that can be rapidly and routinely used in place of the
      previous cumbersome two-step assay. The reaction rates measured with the coupled
      assay display a linear dependence with respect to enzyme concentration over the
      range investigated. The method yields accurate and reliable estimates of the
      enzyme activity in the direction of NAD+ synthesis. Furthermore, we developed an
      HPLC-based method suitable for the assay activity both in the forward and reverse
      directions of the enzymatic reaction. The method appears particularly useful for
      measuring the NMNAT activity when the product is not NAD+ (e.g., in studies using
      alternative substrates), and offers the possibility of monitoring simultaneously
      both the NMNAT-catalyzed reaction and interfering side reactions. This is
      achieved through the HPLC identification and quantitation of metabolites and
      derivatives produced in the reaction mixture during the assay. The two methods
      described here should cover most needs for the assay of NMNAT activity.

PMID- 8572290
TI  - Determination of Cu-containing metallothionein: comparison of Ag saturation
      assay, thiomolybdate assay, and enzyme-linked immunosorbent assay.
AB  - Three methods for the quantification of Cu-containing metallothionein (MT) (Ag
      saturation assay, thiomolybdate assay, and enzyme-linked immunosorbent assay
      (ELISA))  were compared for their ability to recover in vitro prepared standard
      Cu-MT both in absence and presence of rat liver cytosol. Uniform molar
      calibration of the assays was achieved using the nitrogen content of the standard
      Cu-MT measured by the Kjeldahl procedure. With all three methods Cu-MT reliably
      could be quantified. The Ag saturation assay and the thiomolybdate assay,
      dependent on the amount of Cu-MT and the presence of hepatic cytosol, showed a
      tendency to over- or underestimate the theoretical expectation. The ELISA
      generally performed best and moreover was three orders of magnitude more
      sensitive than the other two assays. With all three methods corresponding MT
      levels were found in the Cu-rich liver of a Long-Evans Cinnamon rat.

PMID- 8572291
TI  - Use of fluorogenic substrates for detection and investigation of ectoenzymatic
      hydrolysis of diadenosine polyphosphates: a fluorometric study on chromaffin
      cells.
AB  - A set of procedures to assay and investigate ectoenzymatic hydrolysis of
      diadenosine polyphosphates (ApnA) in both intact cell or plasma membrane
      preparations is described. Procedures are based on the use of the fluorogenic
      ApnA analogs, epsilon-(ApnA), as artificial substrates. It is shown that these
      fluorogenic analogs behave as excellent substrates of the ectoenzyme present in
      cultured chromaffin cells. The ectoenzyme hydrolyzed all epsilon-(ApnA) tested (n
      = 2-6), always producing epsilon-AMP and epsilon-Ado 5'(n - 1) phosphate
      moieties. These released nucleotide moieties were then further catabolized up to
      epsilon-Ado by other ectonucleotidases. Epsilon-(Ap4A) hydrolysis by cultured
      cells displayed Km and Vmax values of 4.1 +/- 1.5 microM and 13.2 +/- 1.3
      pmol/min x 10(6) cells, respectively, as measured by continuous fluorometric
      assays and 3.5 +/- 1.6 microM and 10.0 +/- 1.9 pmol/min x 10(6) cells by
      chromatographic-fluorometric assays. Using plasma membranes, values of 2.5 +/-
      0.8 microM and 669 +/- 59 pmol/min x mg protein for Km and Vmax, respectively,
      were obtained through continuous fluorometric assays. ApnA and GpnG behaved as
      competitors and Ki values for these dinucleotides ranged between 0.7 and 3.5
      microM. The ectoenzyme was activated by Mg2+ and Ca2+ and achieved maximal
      activity in the pH range 8.5-9.0.

PMID- 8572292
TI  - A microplate assay for quantitation of anchorage-independent growth of
      transformed cells.
AB  - We developed a 96-well microplate assay to quantitate anchorage-independent
      growth of transformed cells. Wells of tissue culture microtiter plates are coated
      with poly(2-hydroxyethyl methacrylate) (poly-(HEMA)) to prevent cell attachment,
      and cells suspended in liquid media are seeded into the treated plates. Cell
      growth is assessed by tetrazolium dye reduction or by counting [3H]thymidine
      incorporation into DNA. There appeared to be a close correlation between growth
      in poly(HEMA)-coated plates and colony formation in soft agar, i.e., fibroblasts
      transformed by various oncogene proliferated in the coated plates, whereas their
      normal counterparts did not. Transformed cells on the nonadhesive surface were
      round and formed multicellular spheroids which resembled colonies in soft agar.
      Cells carrying either temperature-sensitive v-src or inducible v-Ki-ras oncogene
      proliferated on poly(HEMA)-coated plates only when they displayed transformed
      phenotype. This method is simple, quick, quantitative, and economical and in many
      cases might be more practical than conventional soft agar colony formation assay
      for measurement of anchorage-independent growth.

PMID- 8572293
TI  - Ligation of hexamers on hexamer templates to produce primers for cycle sequencing
      or the polymerase chain reaction.
AB  - A method is described for the ordered ligation of hexanucleotides (hexamers) in
      solution to produce unique longer oligonucleotides. To form an 18-mer, for
      example, six different hexamers are selected that can base pair unambiguously to
      form a double-stranded complex of indefinite length. In the most efficient
      arrangement, each hexamer forms three complementary base pairs with two other
      hexamers, generating complementary chains of contiguous hexamers with strand
      breaks staggered by three bases. Two adjacent hexamers in one chain contain 5'
      phosphate groups and the others are unphosphorylated. Both T4 and T7 DNA ligase
      can ligate the phosphorylated hexamers to their neighbors in such a complex at
      hexamer concentrations in the 50-100 microM range, producing an 18-mer and
      leaving three unphosphorylated hexamers. Twenty-nine of 34 complexes that
      satisfied the requirements for unambiguous ligation generated the desired 18
      mers, which could be used directly for cycle sequencing or, after removal of the
      unreacted hexamers, for polymerase chain reactions (PCR). Comparable ligation
      reactions also produced 12-, 24-, and 30-mers. With a library of all 4096
      possible hexamers, unambiguous ligation has the potential to produce more than
      82% of all possible 18-mers and could readily supply the oligonucleotides needed
      for DNA sequencing by primer walking, for PCR, or for gene synthesis.

PMID- 8572294
TI  - Inter-Alu polymerase chain reaction: advancements and applications.

PMID- 8572295
TI  - Measurement of sarcoplasmic reticulum function in mammalian skeletal muscle:
      technical aspects.
AB  - Two recently developed methods for measuring the maximal rate of Ca2+ uptake and
      Ca2+ ATPase activity (EC 3.1.6.38) in vitro use muscle homogenate rather than
      isolated sarcoplasmic reticulum (SR). In this study we investigated technical
      aspects of these assays, including specificity and variability of the assays, the
      effect of different freezing treatments on maximal Ca2+ uptake and Ca2+ ATPase
      activity of human and rat muscle homogenate, stability of the homogenate, and the
      modification of the Ca2+ uptake assay to measure Ag(+)-induced Ca2+ release.
      Addition of cyclopiazonic acid (20 microM) blocked Ca2+ uptake, demonstrating
      specificity of the assay. Using frozen muscle homogenate, the inter- and
      intraassay variation for both assays was less than 9%. Whereas homogenates were
      stable to freezing for both Ca2+ uptake and Ca2+ ATPase activity, there was a
      significant (P < 0.05) decrease in activity when muscle was freeze-dried or
      quickly frozen in small pieces. After 1 h on ice, rat muscle homogenate Ca2+
      uptake and Ca2+ ATPase activity had decreased by 6.0% (ns) and 3.6% (P < 0.05),
      respectively; after 3 h, activity had decreased by 15.3 and 14.7%, respectively
      (P < 0.01). The Ca2+ uptake assay was modified to allow measurement of Ag(+)
      induced Ca2+ release. Following homogenate addition, after the SR vesicles were
      loaded with Ca2+ and [Ca2+] had declined to a plateau, AgNO3 (141 microM) was
      added, initiating release of Ca2+ into the assay solution. Addition of
      dithiothreitol (4 mM) blocked the Ag(+)-induced Ca2+ release, demonstrating
      specificity of the assay.

PMID- 8572296
TI  - Application of high-performance liquid chromatography to determination of
      modifier activity in alpha-lactalbumin and other proteins.
AB  - High-performance liquid chromatography has been applied to determination of
      modifier activity in alpha-lactalbumin (alpha-LA). An amino-bonded column
      separates uridine diphosphate (UDP) (product), UDPgalactose (substrate), and
      uridine monophosphate (UMP). From an aliquot of the same sample, a column for
      carbohydrate analysis separates lactose (the other product) and galactose-1,2
      cyclic phosphate (Gal-c-P). Nucleotide peaks are detected by measurement of A262
      and those of carbohydrate by 3H counting, the isotope originating from UDP
      galactose-3H. A pH of 6.3 was taken as optimal for production of UDP since, at
      this level, the unwanted side reaction is minimized, by which UMP and Gal-c-P are
      formed. Thus, the conservation of substrate so effected may have contributed to
      an enhanced production of UDP. The reaction by which UDP and lactose are produced
      was linear for 120 min, as followed by UDP formation, but it continued to at
      least 300 min. Production of lactose was equivalent to that of UDP, when alpha-LA
      was the modifying protein. From a survey of seven other proteins, only lysozyme
      and ovalbumin showed ability to produce UDP. However, failure of the last two
      proteins to produce lactose indicates absence of modifier activity and
      demonstrates the need for monitoring both products.

PMID- 8572297
TI  - Quantitative fluorescence method for continuous measurement of DNA hybridization
      kinetics using a fluorescent intercalator.
AB  - We present a quantitative fluorescence method for continuous measurement of DNA
      or RNA hybridization (including renaturation) kinetics using a fluorescent DNA
      intercalator. The method has high sensitivity and can be used with reaction
      volumes as small as 1 microliter and amounts of DNA around 1 ng. The method is
      based on the observations that (i) for the usual hybridization conditions,
      intercalators such as ethidium bromide bind (intercalate) to double-stranded DNA
      (dsDNA) but not single-stranded DNA or RNA and (ii) there is a large increase in
      fluorescence intensity when intercalators such as ethidium bromide bind to dsDNA.
      In this application, the intercalator can be considered as a quantitative
      indicator of dsDNA concentration. When a small amount of intercalator is added to
      a hybridizing solution, the fluorescence intensity of the intercalators increases
      with increase in dsDNA. The hybridization reaction can thus be monitored by
      continuously recording fluorescence intensity vs time. Because the amount of
      intercalator bound to dsDNA is not necessarily proportional to dsDNA
      concentration, the time-dependent fluorescence intensity graph is not identical
      to the kinetic graph [dsDNA] vs t. However, the fluorescence intensity vs time
      graph can easily be converted to the true [dsDNA] vs t graph by means of an
      experimental calibration graph of fluorescence intensity vs [dsDNA]. This
      calibration graph is obtained in a separate experiment using samples containing
      known amounts of dsDNA in the ethidium bromide buffer used in the kinetic
      measurement. We present results of experimental tests of the intercalator
      technique using ethidium bromide as an intercalator and DNA from Escherichia coli
      and lambda-phage and Poly(I)-Poly(C) RNA hybrids. These DNA and RNA samples have
      Cot1/2 values that cover a range of 10(6). Our experimental results show that (i)
      the kinetics of hybridization are not significantly perturbed by the intercalator
      at concentrations where no more than 10% of the binding sites on DNA or RNA
      hybrids are occupied, (ii) the kinetic graphs obtained by the intercalator
      fluorescence method and corrected with the calibration graph agree with kinetic
      graphs obtained by optical absorbance measurements at 260 nm, and (iii) the
      intercalator technique can be used in the different salt environments often used
      to increase the velocity of the hybridization reaction and at the hybridization
      temperatures (35-75 degrees C) normally used to minimize nonspecific
      hybridization.

PMID- 8572298
TI  - A method for monitoring the glycosylation of recombinant glycoproteins from
      conditioned medium, using fluorophore-assisted carbohydrate electrophoresis.
AB  - We have developed a method for monitoring the N-glycosylation of recombinant
      glycoproteins directly from conditioned medium samples. Proteins in the
      conditioned medium are separated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and electroblotted onto polyvinylidene fluoride membranes. After
      staining the membranes with Coomassie blue, the protein(s) of interest is
      excised. Oligosaccharides are released from the membrane-bound glycoprotein by
      digesting with peptide N4-(acetyl-beta-glucosaminyl) asparagine amidase and
      labeled with the fluorophore 8-aminonaphthalene-1,3,6-trisulfonate (ANTS).
      Labeled oligosaccharides are then separated on polyacrylamide gels which allow
      for the direct comparison of samples. We have shown that recombinant human
      lysosomal hydrolase alpha-galactosidase A is N-glycosylated with both sialylated
      and phosphorylated oligosaccharides. ANTS-labeled oligosaccharide bands from
      alpha-galactosidase A were isolated from polyacrylamide gels. Sialylated and
      phosphorylated bands were identified by shifts in their electrophoretic mobility
      after digesting with neuraminidase or alkaline phosphatase to remove sialic acid
      or phosphate groups, respectively. Using the ANTS-labeled oligosaccharides from
      alpha-galactosidase A, we have shown that polyacrylamide gels can be used to
      resolve sialylated and phosphorylated oligosaccharide structures.

PMID- 8572299
TI  - Facile preparation of inside-out plasma membrane vesicles from tumor cells for
      functional studies of pharmacologically relevant translocating ATPases.
AB  - A reasonably facile and effective procedure is described for the preparation of
      inside-out plasma membrane vesicles from tumor cells. The method incorporates
      nitrogen cavitation, optimized with respect to the applied N2 pressure, in the
      absence of added divalent cations followed by differential centrifugation and
      discontinuous, sucrose gradient centrifugation. With the three tumor cell types
      utilized, multidrug-resistant (MEL/VCR-6) and parental (MEL/O) murine
      erythroleukemia cells and methotrexate-resistant (L1210/R24) L1210 leukemia
      cells, yields were in the range of 8-12 mg of plasma membrane vesicles/10(10)
      cells at a purity of 87-94% with average inside-out sidedness among preparations
      varying from 65 to 93% depending upon the cell type. Inside-out plasma membrane
      vesicles so derived were capable of sustaining ATP-dependent transport inward of
      two common antitumor cytotoxic agents, vinblastine and methotrexate. The former
      was demonstrated with inside-out vesicles from only P-glycoprotein
      overexpressing, multidrug-resistant MEL/VCR-6 cells, while the latter was readily
      demonstrated in inside-out vesicles from all three cell types.

PMID- 8572300
TI  - An immunofiltration apparatus for accelerating the visualization of antigen on
      membrane supports.
AB  - Although proteins can be transferred and bound to a membrane with several
      different methods such as capillary transfer, electroblotting, etc., only the
      "shaker/incubation" method is commonly used for visualization of the proteins. We
      have tested an apparatus for the immunofiltration of solutions through
      nitrocellulose membrane which greatly accelerates the kinetics for the
      visualization of proteins. As a model system, avidin, bound on nitrocellulose
      membrane, was detected with 5-min filtering steps of a 1:2000 dilution of ascites
      of murine monoclonal antibody against avidin followed by a 1:5000 dilution of
      goat anti-mouse IgG-horseradish peroxidase and 0.5 mg/ml chloronapthol in the
      presence of 0.01% peroxide. The same solutions used with 5-min incubation steps
      with the shaker/incubation method could not detect avidin at almost 10 times that
      amount. Further studies with monoclonal antibodies specific for native C-reactive
      protein and modified-CRP, 15.1D6 and 13.3H12 respectively, showed that
      immunofiltration did not result in altered specificity compared to the
      shaker/incubation method. Also, data are presented showing the advantages of a 10
      slot top for the immunofiltration of solutions through distinct areas of a
      membrane.

PMID- 8572301
TI  - Effects of solute multivalence on the evaluation of binding constants by
      biosensor technology: studies with concanavalin A and interleukin-6 as
      partitioning proteins.
AB  - The interaction of concanavalin A with immobilized carboxylmethyldextran has been
      characterized by means of a biosensor based on surface plasmon resonance
      detection. Adsorption and desorption of this bivalent lectin to/from the
      biosensor surface are shown to deviate markedly from pseudo-first-order kinetics,
      an assumption inherent in the usual kinetic approach to the characterization of
      interactions by biosensor technology. Similar results for the interaction of a
      dimeric and hence bivalent form of human interleukin-6 with its receptor
      immobilized on the biosensor plate support the conclusion that this deviation
      from pseudo-first-order kinetics originates from multivalence of the partitioning
      protein. Use of the kinetic approach to characterize the binding of multivalent
      proteins to immobilized affinity sites on the biosensor chip is therefore
      precluded because of nonconformity with the model on which the quantitative
      analysis is based. Instead, an intrinsic binding constant of 2.5 x 10(5) M-1 for
      the interaction of concanavalin A with the carboxymethylated dextran layer
      coating the biosensor chip has been obtained by interpreting the equilibrium
      biosensor responses in terms of expressions developed in the context of
      quantitative affinity chromatography of multivalent partitioning solutes.

PMID- 8572302
TI  - Poly(ADP-ribose) quantification at the femtomole level in mammalian cells.
AB  - ADP-ribose polymers were isolated from living mammalian cells, separated by
      polyacrylamide gel electrophoresis, visualized in the gel with a novel silver
      staining agent, and quantified by computer-aided scanning densitometry. This
      method detects as little as approximately 40 fmol of ADP-ribose polymers of a
      particular size class and reduces the gel exposure times required for
      conventionally radiolabeled polymers from 2 months to about 1 h. The method also
      detects polymers with slow turnover which may be underestimated by techniques
      requiring metabolic radiolabeling of poly(ADP-ribose).

PMID- 8572303
TI  - In situ polymerase chain reaction technique revealed by flow cytometry as a tool
      for gene detection.
AB  - We report a methodology for detecting specific DNA sequences directly inside
      cells, combining in situ PCR and flow cytometry. This technique is based on in
      situ PCR performed in the presence of digoxigenin-labeled dUTP to obtain a
      digoxigenin-labeled amplicon, which is then revealed by an anti-digoxigenin
      polyclonal antibody directly conjugated to fluorescein. Fluorescence intensity is
      next evaluated by flow cytometry. Our experimental models were represented by the
      lymphoblastoid cell lines 8E5LAV, carrying an integrated HIV-1 DNA proviral copy
      per cell, and A.301, infected in vitro with HIV-1 (strain IIIB). The technique is
      described in detail with particular attention to the optimization of critical
      fixation and permeabilization steps. This method allows not only the detection
      but also an accurate quantification of the number of positive cells in a
      background of negative cells. Moreover, it has the potentiality to develop into a
      multiparametric method for the simultaneous study of specific DNA or RNA
      sequences and surface or intracellular markers.

PMID- 8572304
TI  - HIV-1 protease specificity derived from a complex mixture of synthetic
      substrates.
AB  - A rapid and semiquantitative method is described for determining the relative
      kcat/Km for individual peptides in defined substrate mixtures. The method
      utilizes electrospray ionization/mass spectrometry alone to semiquantitatively
      determine relative peptide substrate turnover rates. Unlike previous studies, in
      which chromatographic separation of individual peptide species was required, this
      mass spectrometric-based method relies strictly on the ability to ionize and
      detect simultaneously all peptide species in a defined mixture. Differences in
      the ion intensities of the individual components before and after incubation with
      protease are used to semiquantitatively determine preferred substrates. This
      method was used to the identify preferred peptide substrates for HIV-1 protease.
      Optimal substrates were identified from a defined synthetic peptide substrate
      mixture based on Ser-Gln-Asn-Tyr-Pro-Ile-Val, where the P1' proline was
      substituted with 20 naturally occurring amino acids. The hydrophobic residues
      Leu, Ile, Val, Phe, and Tyr were preferred in addition to Pro at the P1' site.
      The results were corroborated by performing the more laborious HPLC/Frit-fast
      atom bombardment/MS analyses.

PMID- 8572305
TI  - Use of selective tyrosine kinase blockers to monitor growth factor receptor
      dephosphorylation in intact cells.
AB  - A novel assay was developed which allows measuring the activity of protein
      tyrosine phosphatases (PTPases) downregulating the signaling activity of the
      receptors for platelet-derived growth factor (PDGF) or epidermal growth factor
      (EGF) in intact Swiss 3T3 cells and nerve growth factor (TrkA) in TrkA
      overexpressing PC12 cells. The assay is based on the inhibition of the receptor
      tyrosine kinases by specific inhibitors which enter the cells rapidly and do not
      affect the activity of PTPases. Thereafter, the decay of phosphotyrosine in the
      autophosphorylated receptors is monitored by immunoblotting with anti
      phosphotyrosine antibodies. The dephosphorylation kinetics of EGF receptors and
      PDGF receptors in Swiss 3T3 cells as measured with this assay were found to be
      strikingly different. EGF receptors are almost completely dephosphorylated after
      2 min at room temperature, whereas PDGF receptors are dephosphorylated only by
      50% after 5 min. These data agree with previous findings about receptor
      dephosphorylation kinetics in isolated Swiss 3T3 cell membranes employing
      conventional dephosphorylation assays. The novel assay will facilitate
      characterization of the hitherto not identified receptor-directed PTPases for
      PDGF receptors, EGF receptors, and TrkA. The assay principle is general and
      should be applicable to any PTPases and their substrates, provided specific
      inhibitors for the respective kinases are available. Furthermore, it can be
      applied to screen for regulator molecules of specific PTPases in their
      physiological environment.

PMID- 8572306
TI  - Surface plasmon resonance detection and multispot sensing for direct monitoring
      of interactions involving low-molecular-weight analytes and for determination of
      low affinities.
AB  - Surface plasmon resonance detection allows direct observation of molecular
      interactions between an analyte in solution and its immobilized binding partner.
      The use of simultaneous monitoring of interaction events on multiple sensing
      surfaces, with varying amounts of immobilized receptor, for detection of low
      molecular-weight analytes and for determination of low affinities was
      investigated. Using multispot sensing and BIAcore 2000 instrumentation, analytes
      as small as 180 Da were detected and affinities in the 50 microM range could be
      determined. The use of multispot sensing thus extends direct interaction analysis
      to include low-molecular-weight analytes and low-affinity interactions.

PMID- 8572307
TI  - Capillary gel electrophoresis as a method to determine ligation efficiency.
AB  - A capillary gel electrophoresis (CGE) method is described for detection of the
      formation of circular DNA ligation products as an aid in the prediction of
      ligated DNA competent cell transformation efficiency. The separation is based
      upon the differences in the relative migrations of linear and circular DNA
      molecules of the same size. In CGE, circular ligation products are shifted
      significantly from linear DNA fragments of comparable size (to 40-42 min from 32
      33 min migration time) in the presence of an intercalating dye. CGE separation
      and detection of circularized DNA can be correlated with transformation
      efficiencies of > 10(6) colony-forming units (CFU, colonies/micrograms/ml) or the
      high efficiency desired for phagemid display and cell expression libraries. CGE
      has several advantages over slab gel electrophoresis: (i) only a minute quantity
      (approximately 250 CFU or 0.02%) of the total library is sacrificed for analysis,
      (ii) verification of the circularized ligation products is easier by CGE, and
      (iii) CGE analysis of ligation success can be accomplished in less than 2 h,
      prior to transforming competent cells.

PMID- 8572308
TI  - An ultrasensitive, continuous fluorometric assay for calpain activity.
AB  - A rapid, continuous assay for calcium-activated neutral protease activity is
      described. This assay is based on monitoring the elevation in fluorescence
      intensity that occurs upon calpainolytic digestion of dichlorotriazinylamino
      fluorescein-labeled microtubule-associated protein 2. Tedious separation of
      peptide products from the protein substrate in this rapid assay is unnecessary,
      which thus offers two remarkable advantages over conventional caseinolytic assay
      procedures: (i) it raises sensitivity of detection by about three orders of
      magnitude, allowing the quantitative determination of calpain in the high
      picogram range in 10 min; and (ii) it permits a continuous detection of activity,
      which may prove invaluable in enzyme-mechanism studies that require pre-steady
      state measurements. Other features and advantages of the assay, along with its
      limitations, are discussed in detail.

PMID- 8572309
TI  - Determination of aldehydes and other lipid peroxidation products in biological
      samples by gas chromatography-mass spectrometry.
AB  - The extremely broad spectrum of the biological effects of aldehydic lipid
      peroxidation products has necessitated the development of a technique that can
      quantitate all of the aldehydes formed in biological materials. The proposed
      method is based on the use of O-(2, 3, 4, 5, 6-pentafluorobenzyl) hydroxylamine
      hydrochloride (PFBHA.HCl) to form the O-pentafluorobenzyl-oxime (PFB-oxime)
      derivatives of 22 saturated and unsaturated aldehydes (C2-C12) including hexanal,
      4-hydroxy-non-2-enal (HNE), and malondialdehyde (MDA), followed by
      trimethylsilylation of the hydroxyl group to trimethylsilyl (TMS) ethers. The PFB
      oxime-TMS derivatives were analyzed by capillary column gas chromatography
      negative-ion chemical ionization mass spectrometry (GC-NICIMS) with ammonia as
      reagent gas. Quantitation was achieved using benzaldehyde-ring-D5 as an internal
      standard in selected ion recording (SIR) mode. Standard curves were linear (r >
      0.99) for all individual aldehydes. The detection limit was between 50 and 100
      fmol per 1 microliter injected aldehyde. Recovery of all aldehydes from urine,
      plasma, and tissue homogenate was over 85%, except HNE, trans-2-octenal and trans
      2,-cis-6-nonadienal from plasma and tissue sample, which were between 60 and 80%,
      suggesting these aldehydes may bind to protein and lipid components, especially
      to SH groups of proteins. The high sensitivity of this method allows the
      measurement of physiological aldehyde levels in biological samples. The products
      of aldehyde metabolism can also be measured by this assay.

PMID- 8572310
TI  - Biotinylated hyaluronic acid as a probe for identifying hyaluronic acid-binding
      proteins.
AB  - The glycosaminoglycans hyaluronan (HA), heparin, and chondroitin sulfate were
      biotinylated using biotin-x-hydrazide (biotin-epsilon-aminocaproyl hydrozyde) in
      conjunction with N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride, an
      activating agent for carboxyl groups. The biotin-x-hydrazide was shown to be
      coupled directly to the glycosaminoglycans in enzymatic digestions and
      competition experiments. The biotinylated HA was shown to bind to link protein
      and receptor for hyaluronic acid-mediated motility, two proteins known to bind
      HA. The labeled HA was used as a probe to detect known HA-binding proteins in
      chicken cartilage extract and to identify new HA-binding motifs in the G3 domain
      of the proteoglycan aggrecan. The significance of the biotinylation of HA,
      heparin, and chondroitin sulfate A are discussed.

PMID- 8572311
TI  - Capillary electrophoretic separation and laser-induced fluorescence detection of
      the major DNA adducts of cisplatin and carboplatin.
AB  - Micellar electrokinetic capillary chromatographic separation of a dansylated
      mixture of normal nucleotides and platinated cross-link adducts of d(pGpG) and
      d(pApG) was optimized with baseline resolution. The introduction of a laser
      induced fluorescence (LIF) detector overcame the lack of sensitivity
      characteristic of capillary electrophoresis (CE) due to the small injection
      volume and the short optical path length. CE/LIF was able to detect 1
      adduct/10(4) normal nucleotides/micrograms DNA by fluorescence postlabeling
      assay. The enrichment of the adduct, prior to dansylation, enhanced the detection
      limit to 1 adduct/10(7) normal nucleotides/micrograms DNA. Calf thymus DNA was
      reacted in vitro with cisplatin and carboplatin with total input drug/nucleotide
      ratios of 0.05 and 0.5, respectively. A2780 human ovarian carcinoma cells were
      exposed in culture to 25 microM cisplatin for 2 h. The cells were incubated with
      drug-free medium for 3 h before harvesting. The identification of the cross-link
      adducts in modified DNA was confirmed by cochromatography with authentic markers.
      The same 1,2-intrastrand cross-link adducts were induced by both cisplatin and
      its second-generation drug carboplatin. This report has demonstrated, for the
      first time, the utility of CE/LIF as an analytical tool for assaying DNA damage
      [corrected].

PMID- 8572312
TI  - High-performance liquid chromatography analysis of oxidized and reduced pyridine
      dinucleotides in specific brain regions.
AB  - An ultrasensitive HPLC method has been developed for measuring NADP+, NADPH,
      NAD+, and NADH. A simple, rapid reaction of the oxidized nucleotides with cyanide
      in basic solution leads to two stable fluorescent products and allows all four
      nucleotides to be separated and quantitated on one chromatogram. Furthermore,
      only one extraction is needed, rather than prior procedures which require one
      acid extraction (for oxidized species) and one basic extraction (for reduced
      species). This method is particularly useful in quantitating pyridine
      dinucleotides in rodent brain, where no current method is adequate to quantitate
      the small amounts contained in various brain regions. The assay is sensitive
      enough to measure individual brain regions down to 10 mg of tissue. Due to the
      involvement of NAD(P)H enzymatic systems in combating oxidative stress it is
      important to be able to assess levels regionally in brain diseases.

PMID- 8572313
TI  - Chaotropic solvents increase the critical micellar concentrations of detergents.
AB  - Monomer detergent concentrations of Triton X-100, Chaps (3-[(3-cholamidopropyl)
      dimethylammonio]-1-propanesulfonate), and sodium dodecyl sulfate in guanidine
      hydrochloride, formamide, and urea solutions were measured by an ultrafiltration
      procedure. This simple and rapid procedure effectively separated the monomer
      forms of these detergents from their respective micelle forms. Critical micellar
      concentrations of these detergents in water measured by this procedure agreed
      well with previously reported values. Both ionic and nonionic chaotropic agents,
      e.g., guanidine hydrochloride, formamide, and urea, are demonstrated to
      significantly shift the equilibrium between the monomer and the micellar form of
      various detergents toward the direction of monomer in a concentration-dependent
      manner. Thus, monomer/micelle ratio of detergents in solution can be manipulated
      over a wide range by the concomitant use of chaotropic solvents. This has direct
      applications in experiments involving destruction of biomembranes and
      solubilization of hydrophobic molecules in aqueous solutions.

PMID- 8572314
TI  - Characterization of nonradioactive assays for cobalamin-dependent and cobalamin
      independent methionine synthase enzymes.
AB  - Methionine synthase enzymes catalyze methyl group transfer from 5
      methyltetrahydrofolate to homocysteine to give methionine and tetrahydrofolate.
      Assays for this enzyme activity usually monitor transfer of a 14C-methyl group
      from the N5-position of methyltetrahydrofolate to homocysteine to produce 14C
      methionine that must be purified by anion-exchange chromatography. Alternatively,
      tetrahydrofolate may be derivatized with a formylating agent under acidic
      conditions to produce methenyltetrahydrofolate. We report optimization of this
      reaction for assay of cobalamin-dependent methionine synthase to give an
      economical method for determining enzyme activity that does not require the use
      of radioactive compounds. By heating for 10 min in 1 N hydrochloric acid
      containing 12% formic acid, the enzymatic product tetrahydrofolate is converted
      into methenyltetrahydrofolate, which absorbs light at 350 nm, while residual
      substrate 5-methyltetrahydrofolate does not contribute to the absorbance at 350
      nm. The assay allows the derivatized product to be characterized in situ with a
      minimal increase in volume upon acidification. The results of the
      spectrophotometric assay given here have been compared with the radioactive assay
      to confirm the validity of the derivatization under the assay conditions. We also
      report the extension of this assay method for use in activity measurements of
      cobalamin-independent methionine synthase.

PMID- 8572315
TI  - Purification of aminoacyl-tRNA by affinity chromatography on immobilized Thermus
      thermophilus EF-Tu.GTP.
AB  - Elongation factor Tu from Thermus thermophilus containing six histidine residues
      on its C-terminus, EF-Tu(CHis6), was used for purification of aminoacyl-tRNA
      isoacceptors, from aminoacylated bulk tRNA, by affinity chromatography. Preformed
      aminoacyl-tRNA.EF-Tu(CHis6).GTP ternary complexes were immobilized on Ni(2+)
      nitriloacetic acid agarose and the aminoacyl-tRNA was eluted at high ionic
      strength or with buffers containing GDP. Compared to alternative methods, the
      reported immobilization by C-terminal histidine residues does not lead to loss of
      EF-Tu's affinity for aminoacyl-tRNA. The method is well suited for preparative
      isolation of aminoacylated tRNA isoacceptors and as an analytical tool to test
      tRNA composition and aminoacylation of tRNA in crude cellular extracts.

PMID- 8572316
TI  - A video technique for the quantification of DNA in gels stained with ethidium
      bromide.
AB  - We have developed a method for the comparison of quantitative differences between
      nucleic acid samples run on agarose gels. It is useful for the analysis of
      digested genomic DNA and RNA preparations, as well as for clamped homogeneous
      electric field gel analysis of damaged chromosomal DNA. The technique utilizes a
      standard color charge-coupled device video camera, a microcomputer, and
      commercially available software. While not as elaborate as other image analysis
      systems, our method is suitable for many purposes and can be set up for a
      relatively low cost. In principle, any system capable of recording 24-bit color
      scans and measuring pixel color intensity could be used.

PMID- 8572317
TI  - Rapid purification of tubulin from tissue and tissue culture cells using solid
      phase ion exchange.
AB  - Tubulin can be purified from tissue or tissue culture cell starting material in
      less than 6 h using a combination of a solid-phase ion exchanger and one cycle of
      temperature-dependent polymerization and depolymerization. The use of a solid
      phase ion exchanger (MemSep DEAE) greatly reduces the time required for the ion
      exchange step compared to conventional exchangers. The use of sodium glutamate to
      elute tubulin from the exchanger stabilizes the protein and facilitates the final
      polymerization step of the purification. The procedure can be performed
      successfully with less than 100 mg of tissue culture cell protein as starting
      material. The final material is > 90% pure and active as judged by sodium dodecyl
      sulfate-gels and by binding of the bicyclic colchicine analog 2-methoxy-5
      (2',3',4'-trimethoxyphenyl)-tropone.

PMID- 8572318
TI  - Spectrophotometric method for determination of carbonyls in oxidatively modified
      apolipoprotein B of human low-density lipoproteins.

PMID- 8572319
TI  - Reversible oxidative aggregation obstructs specific proteolytic cleavage of
      glutathione S-transferase fusion proteins.

PMID- 8572320
TI  - Construction of a retroviral vector incorporating mouse VL30 retrotransposon
      derived, transcriptional regulatory sequences.

PMID- 8572321
TI  - Resolution of uncertainties in restriction maps of cosmid clones by "sequencing
      stitching".

PMID- 8572322
TI  - Cardiac outcomes after regional or general anesthesia. Do we have the answer?

PMID- 8572324
TI  - Propofol attenuates hydrogen peroxide-induced mechanical and metabolic
      derangements in the isolated rat heart.
AB  - BACKGROUND: Oxygen-derived free radicals are involved in tissue damage during
      myocardial ischemia and reperfusion. Recent in vitro studies have demonstrated
      that a beneficial effect of propofol lies on its free radical scavenging
      properties. The current study, therefore, examined whether propofol is effective
      against the mechanical and metabolic damage induced by exogenously administered
      hydrogen peroxide in the isolated rat heart. METHODS: Rat hearts were perfused
      aerobically with Krebs-Henseleit bicarbonate buffer at a constant flow rate
      according to Langendorff's technique, while being paced electrically. Hearts were
      studied in control Krebs-Henseleit bicarbonate buffer, with Intralipid vehicle,
      with 25 microM or 50 microM propofol for 40 min, and with 50 microM propofol for
      30 min followed by Intralipid for 10 min. A similar set of hearts was treated
      with hydrogen peroxide for 4 min, either in the absence of or beginning 10 min
      after Intralipid or propofol infusion. Left ventricular pressure was recorded as
      an index of mechanical function. The tissue concentrations of adenosine
      triphosphate, adenosine diphosphate, adenosine monophosphate, and creatine
      phosphate were measured as indices of energy metabolism. The tissue concentration
      of malondialdehyde was measured to evaluate lipid peroxidation. RESULTS: Hydrogen
      peroxide (600 microM) significantly increased the left ventricular end-diastolic
      pressure, decreased the left ventricular developed pressure (i.e., it produced
      mechanical dysfunction), and decreased tissue concentrations of adenosine
      triphosphate and creatine phosphate (i.e., metabolic damage). Hydrogen peroxide
      also increased the tissue concentration of malondialdehyde. These mechanical and
      metabolic alterations induced by hydrogen peroxide were significantly attenuated
      by propofol (25 microM or 50 microM), while the increase in malondialdehyde was
      completely suppressed by propofol. CONCLUSIONS: The current study demonstrates
      that in the isolated heart, propofol attenuates both mechanical and metabolic
      changes induced by exogenously applied hydrogen peroxide. The beneficial action
      of propofol is probably correlated with reduction of the hydrogen peroxide
      induced lipid peroxidation.

PMID- 8572323
TI  - Effect of volatile anesthetics on hydrogen peroxide-induced injury in aortic and
      pulmonary arterial endothelial cells.
AB  - BACKGROUND: Oxidant damage to endothelial cells occurs during inflammation and
      reperfusion after ischemia, mediated in part by endogenously produced hydrogen
      peroxide (H2O2). Previous studies have established a role for increased cytosolic
      calcium in the mechanism of endothelial oxidant injury, and have suggested that
      volatile anesthetics may exacerbate oxidant injury in pulmonary endothelium.
      However, the effect of volatile anesthetics on oxidant injury to systemic
      arterial endothelial cells, and their effect on oxidant-related changes in
      cytosolic calcium homeostasis, have not been reported previously. METHODS:
      Primary cultures of human aortic and pulmonary arterial endothelial cells were
      studied. The rate of cell death after H2O2 exposure was determined in cell
      suspension by propidium iodide fluorimetry and lactate dehydrogenase release. The
      final extent of cell death 24 h after H2O2 exposure was determined in monolayer
      cultures by methyl thiazolyl tetrazolium reduction. Cytosolic calcium and cell
      death were determined in single cells using fura-2 and propidium iodide imaging
      with digitized, multiparameter, fluorescent video microscopy. RESULTS: In aortic
      endothelial cells, clinical concentrations of halothane (1.0%) and isoflurane
      (1.5%) decreased both the rate of cell death and the final extent of cell death
      after H2O2 exposure, with halothane being more protective. Supraclinical
      concentrations of halothane (2.7%) and isoflurane (4.0%) were less protective. In
      pulmonary arterial endothelial cells, halothane and isoflurane had essentially no
      effect on H2O2-mediated cell death. The protective effect of anesthetic in aortic
      endothelial cells was not due to an enhanced removal of H2O2 by endogenous
      enzymes. Hydrogen peroxide exposure caused a large increase in cytosolic calcium
      well before cell death, and this was moderated by anesthetic treatment.
      CONCLUSIONS: The effect of volatile anesthetics on oxidant injury to endothelial
      cells may differ between cells derived from systemic and pulmonary vascular beds.
      Halothane, and to a lesser extent, isoflurane, protects against oxidant injury in
      aortic endothelial cells. The mechanism of protection may involve modulation of
      the interaction of H2O2 with vital cellular constituents, and/or amelioration of
      the toxic increase in cytosolic calcium that follows such interaction.

PMID- 8572325
TI  - Effect of blood pressure changes on air flow dynamics in the upper airway of the
      decerebrate cat.
AB  - BACKGROUND: Previous studies suggest that upper airway neuromuscular activity can
      be affected by changes in blood pressure via a baroreceptor-mediated mechanism.
      It was hypothesized that increases in blood pressure would increase upper airway
      collapsibility predisposing to airway obstruction at a flow-limiting site in the
      hypopharynx. METHODS: To examine the effect of blood pressure on upper airway
      function, maximal inspiratory air flow was determined through the isolated feline
      upper airway before, during, and after intravenous infusion of phenylephrine (10
      20 micrograms.kg-1.min) in six decerebrate, tracheotomized cats. Inspiratory
      flow, hypopharyngeal pressure, and pressure at the site of pharyngeal collapse
      were recorded as hypopharyngeal pressure was rapidly decreased to achieve
      inspiratory flow limitation in the isolated upper airway. Pressure-flow
      relationships were used to determine maximal inspiratory air flow and its
      mechanical determinants, the upper airway critical pressure (a measure of
      pharyngeal collapsibility), and the nasal resistance upstream to the site of flow
      limitation. RESULTS: An increased mean arterial blood pressure of 71 +/- 16 mmHg
      (mean +/- SD) was associated with significant decrease in maximal inspiratory air
      flow from 147 +/- 38 ml/s to 115 +/- 27 ml.sec-1 (P < 0.01). The decrease in
      maximal inspiratory air flow was associated with an increase in upper airway
      critical pressure from -8.1 +/- 3.8 to -5.7 +/- 3.7 cm H2O (p < 0.02), with no
      significant change in nasal resistance. When blood pressure was decreased to
      baseline by discontinuing the phenylephrine infusion, maximal inspiratory air
      flow and upper airway critical pressure returned to their baseline values.
      CONCLUSIONS: Increased blood pressure increased the severity of upper airway air
      flow obstruction by increasing pharyngeal collapsibility. Previous studies
      relating baroreceptor activity to neuromuscular regulation of upper airway tone,
      are consistent with this effect being mediated by afferent activity from
      baroreceptors. These findings warrant further study because they suggest the
      possibility that upper airway obstruction in postoperative patients could either
      be caused or exacerbated by an increase in blood pressure.

PMID- 8572326
TI  - Effects of ventilation on hemodynamics and myocardial blood flow during active
      compression-decompression resuscitation in pigs.
AB  - BACKGROUND: Active compression-decompression (ACD) improves hemodynamics and
      vital organ blood flow during cardiopulmonary resuscitation. The effects of
      intermittent positive pressure ventilation (IPPV) on ACD have not been studied.
      This study was designed to compare the effects of ACD with and without IPPV on
      gas exchange, hemodynamics, and myocardial blood flow. METHODS: After 30 s
      ventricular fibrillation, 14 tracheally intubated pigs were allocated to receive
      either ACD combined with IPPV (ACD-IPPV) or ACD alone. In animals treated with
      ACD-IPPV, the lungs were ventilated using a servo ventilator. Animals treated
      with ACD received 100% oxygen by a reservoir but ventilation was not assisted.
      RESULTS: Minute ventilation (median) was 6.5 and 6.1 l/min after 1 and 7 min of
      ACD-IPPV, and was 4.2 and 1.6 l/min after 1 and 7 min of ACD. In contrast to ACD
      IPPV, PaO2 was less and PaCO2 was greater with ACD. Mean arterial (53 and 40
      mmHg; P < 0.05) and mean central venous pressure (25 and 14 mmHg; P < 0.01) were
      greater during ACD-IPPV as compared with ACD. After administration of epinephrine
      0.2 mg/kg, myocardial blood flow increased only in ACD-IPPV treated animals, and
      5 min after epinephrine administration, myocardial blood flow was greater during
      ACD-IPPV (33 ml.min-1.100 g-1) as compared with ACD (15 ml.min-1.100 g-1; P <
      0.05). Restoration of spontaneous circulation could be achieved only in animals
      subjected to ACD-IPPV. CONCLUSIONS: Gas exchange was critically impaired during
      the late phase of ACD. Compared with ACD-IPPV, myocardial blood flow was less
      preserved with ACD and was too low to achieve restoration of spontaneous
      circulation.

PMID- 8572327
TI  - Tourniquet-induced exsanguination in patients requiring lower limb surgery. An
      ischemia-reperfusion model of oxidant and antioxidant metabolism.
AB  - BACKGROUND: Surgically induced ischemia and reperfusion is frequently accompanied
      by local and remote organ injury. It was hypothesized that this procedure may
      produce injurious oxidants such as hydrogen peroxide (H2O2), which, if
      unscavenged, will generate the highly toxic hydroxyl radical (.OH). Accordingly,
      it was proposed that tourniquet-induced exsanguination for limb surgery may be a
      useful ischemia-reperfusion model to investigate the presence of oxidants,
      particularly H2O2. METHODS: In ten patients undergoing knee surgery, catheters
      were placed in the femoral vein of the limb operated on for collection of local
      blood and in a vein of the arm for sampling of systemic blood. Tourniquet-induced
      limb exsanguination was induced for about 2 h. After tourniquet release
      (reperfusion), blood samples were collected during a 2-h period for measurement
      of H2O2, xanthine oxidase activity, xanthine, uric acid (UA), glutathione, and
      glutathione disulfide. RESULTS: At 30 s of reperfusion, H2O2 concentrations
      increased (approximately 90%) from 133 +/- 5 to 248 +/- 8 nmol.ml-1 (P < 0.05) in
      local blood samples, but no change was evident in systemic blood. However, in
      both local and systemic blood, xanthine oxidase activity increased approximately
      90% (1.91 +/- 0.07 to 3.93 +/- 0.41 and 2.19 +/- 0.07 to 3.57 +/- 0.12 nmol UA.ml
      1.min-1, respectively) as did glutathione concentrations (1.27 +/- 0.04 to 2.69
      +/- 0.14 and 1.27 +/- 0.03 to 2.43 +/- 0.13 mumol.ml-1, respectively). At 5 min
      reperfusion, in local blood, H2O2 concentrations and xanthine oxidase activity
      peaked at 796 +/- 38 nmol.ml-1 (approximately 500%) and 11.69 +/- 1.46 nmol UA.ml
      1.min-1 (approximately 520%), respectively. In local blood, xanthine and UA
      increased from 1.49 +/- 0.07 to 8.36 +/- 0.33 nmol.ml-1 and 2.69 +/- 0.16 to 3.90
      +/- 0.18 mumol.ml-1, respectively, whereas glutathione and glutathione disulfide
      increased to 5.13 +/- 0.36 mumol.ml-1 and 0.514 +/- 0.092 nmol.ml-1,
      respectively. In systemic blood, xanthine oxidase activity peaked at 4.75 +/-
      0.20 UA nmol.ml-1.min-1. At 10 min reperfusion, local blood glutathione and UA
      peaked at 7.08 +/- 0.46 mumol.ml-1 and 4.67 +/- 0.26 mumol.ml-1, respectively,
      while the other metabolites decreased significantly toward pretourniquet levels.
      From 20 to 120 min, most metabolites returned to pretourniquet levels; however,
      local and systemic blood xanthine oxidase activity remained increased 3.76 +/-
      0.29 and 3.57 +/- 0.37 nmol UA.ml-1.min-1, respectively. Systemic blood H2O2 was
      never increased during the study. During the burst period (approximately 5-10
      min), local blood H2O2 concentrations and xanthine oxidase activities were highly
      correlated (r = 0.999). CONCLUSIONS: These studies suggest that tourniquet
      induced exsanguination for limb surgery is a significant source for toxic oxygen
      production in the form of H2O2 and that xanthine oxidase is probably the H2O2
      generating enzyme that is formed during the ischemia-reperfusion event. In
      contrast to the reperfused leg, the absence of H2O2 in arm blood demonstrated a
      balanced oxidant scavenging in the systemic circulation, despite the persistent
      increase in systemic xanthine oxidase activity.

PMID- 8572328
TI  - Intravenous opioids stimulate norepinephrine and acetylcholine release in spinal
      cord dorsal horn. Systematic studies in sheep and an observation in a human.
AB  - BACKGROUND: Opioids produce analgesia by direct effects as well as by activating
      neural pathways that release nonopioid transmitters. This study tested whether
      systematically administered opioids activate descending spinal noradrenergic and
      cholinergic pathways. METHODS: The effect of intravenous morphine on
      cerebrospinal fluid and dorsal horn microdialysate concentrations of
      norepinephrine and acetylcholine was examined in 20 sheep. Animals received
      either intravenous morphine or fentanyl alone, or morphine plus intravenous
      naloxone or intrathecal idazoxan. RESULTS: Intravenous morphine (0, 0.5, 1 mg/kg,
      intravenous) produced dose-dependent increases in cerebrospinal fluid
      norepinephrine and acetylcholine, but not epinephrine or dopamine. Morphine's
      effect was blocked by intravenous naloxone and by intrathecal idazoxan. In
      microdialysis experiments, intravenous morphine increased the concentration of
      norepinephrine and acetylcholine, but not epinephrine or dopamine, in the dorsal
      horn. In contrast, intravenous morphine exerted no effect on any of these
      monoamines in the ventral horn. Intravenous naloxone and cervical cord
      transection each blocked morphine's effect on dorsal horn norepinephrine.
      CONCLUSIONS: These results support functional studies that indicate that
      systematically administered opioids cause spinal norepinephrine and acetylcholine
      release by a naloxone-sensitive mechanism. Idazoxan blockade of morphine's
      effects on cerebrospinal fluid norepinephrine was unexpected, and suggests that
      both norepinephrine and acetylcholine release in the spinal cord may be regulated
      by alpha 2-adrenoceptors. Microdialysis experiments suggest increased
      norepinephrine and acetylcholine levels in cerebrospinal fluid resulted from
      intravenous morphine-induced activation of bulbospinal pathways.

PMID- 8572329
TI  - Interaction of nondepolarizing muscle relaxants with M2 and M3 muscarinic
      receptors in guinea pig lung and heart.
AB  - BACKGROUND: Neuromuscular blocking agents such as gallamine and pancuronium bind
      to muscarinic cholinergic receptors and alter parasympathetically mediated airway
      caliber and heart rate. In the lungs, acetylcholine induces bronchoconstriction
      via M3 muscarinic receptors on airway smooth muscle, whereas in the heart M2
      muscarinic receptors mediate bradycardia. Moreover, release of acetylcholine from
      parasympathetic nerves in the lung is decreased by inhibitory M2 receptors on the
      nerves, which represent a negative feedback system. Blockade of these receptors
      potentiates vagally induced bronchoconstriction, which may be clinically
      important if the M3 receptors on airway muscle are not blocked. These experiments
      were designed to examine the effects of the newer, nondepolarizing muscle
      relaxants pipecuronium, doxacurium, and mivacurium on pulmonary and cardiac
      muscarinic receptors. METHODS: Guinea pigs were anesthetized with urethane,
      paralyzed with succinylcholine, and their lungs mechanically ventilated.
      Pulmonary inflation pressure and heart rate were measured before and after
      electrical stimulation of both vagus nerves to evaluate prejunctional M2
      muscarinic receptor function and after intravenous acetylcholine to evaluate
      postjunctional M3 and M2 receptor function in the presence of increasing
      concentrations of pancuronium, mivacurium, pipecuronium, and doxacurium. RESULTS:
      Pancuronium was an antagonist for M2 and M3 muscarinic receptors. Mivacurium was
      a more potent antagonist of M3 than M2 receptors. Pipecuronium was an antagonist
      of M2 but not M3 receptors. Doxacurium was not an antagonist of either M2 or M3
      muscarinic receptors. Only pancuronium and pipecuronium potentiated vagally
      induced bronchoconstriction. With pipecuronium, the potentiation occurred at
      concentrations greater than those used clinically. CONCLUSIONS: Although
      pipecuronium is an M2 receptor antagonist with no M3 receptor antagonist
      properties, potentiation of reflex-induced bronchoconstriction is unlikely,
      because this effect occurred only at doses greater than those used clinically.

PMID- 8572330
TI  - New ultrathin-walled endotracheal tube with a novel laryngeal seal design. Long
      term evaluation in sheep.
AB  - BACKGROUND: A new endotracheal tube (ETT) was fabricated and tested in sheep. It
      had no tracheal cuff; airway seal was achieved at the level of the glottis
      through a no-pressure seal made of "gills"; the laryngeal portion was oval
      shaped; and the wall thickness was reduced to 0.2 mm. METHODS: Sheep were
      tracheally intubated either with a standard tube or with the new tube, and their
      lungs were mechanically ventilated for 1 or 3 days. Air leak was recorded at
      different peak inspiratory pressures (PIPs). Liquid seepage into the trachea was
      assessed using an indicator dye. Tracheolaryngeal lesions were scored grossly and
      histologically. RESULTS: There was no air leak up to 40 cmH2O of PIP, in either
      group, in short- and long-term studies. Methylene blue leaked across the cuff in
      two sheep with standard ETTs. No dye leaked across the gills with the new ETTs.
      In the new ETT group, the trachea appeared better preserved, grossly and
      histologically, than in the standard ETT group at both 1 and 3 days (P < 0.05).
      At day 1, the larynx and vocal cords appeared grossly less injured in the new ETT
      group (P < 0.05), whereas there was no difference at day 3. Histology did not
      show significant difference on vocal cords, epiglottis, and larynx between the
      two groups at any time. CONCLUSIONS: The novel, no-pressure seal design of the
      new ETT is highly effective in preventing air leak and aspiration. It causes no
      significant tracheal injury.

PMID- 8572331
TI  - Muscarinic signaling in the central nervous system. Recent developments and
      anesthetic implications.
AB  - During the last decade, major advances have been made in our understanding of the
      physiology and pharmacology of CNS muscarinic signaling. It is time to emphasize
      that the well-known peripheral parasympathetic and cardiovascular actions
      represent only one component of muscarinic signaling. Interestingly, many new
      findings have the potential to influence the practice of anesthesiology.
      Inhibition of muscarinic signaling may explain some of the anesthetic state, and
      subtype-selective drugs may allow wider perioperative manipulation of CNS
      muscarinic systems. The next years will doubtlessly see progress in this area,
      and our specialty may well reap the benefits.

PMID- 8572332
TI  - Richard von Foregger, Ph.D., 1872-1960. Manufacturer of anesthesia equipment.

PMID- 8572333
TI  - Adult rat brain-slice preparation for nuclear magnetic resonance spectroscopy
      studies of hypoxia.
AB  - BACKGROUND: When perfused neonatal brain slices are studied ex vivo with nuclear
      magnetic resonance (NMR) spectroscopy, it is possible to use 31P detection to
      monitor levels of intracellular adenosine triphosphate (ATP), cytosolic pH, and
      other high-energy phosphates and 1H detection to monitor lactate and glutamate.
      Adult brain slices of high metabolic integrity are more difficult to obtain for
      such studies, because the adult cranium is thicker, and postdecapitation revival
      time is shorter. A common clinical anesthesia phenomenon--loss of temperature
      regulation during anesthesia, with surface cooling and deep hypothermia, was used
      to obtain high-quality adult rat cerebrocortical slices for NMR studies. METHODS:
      Spontaneously breathing adult rats (350 g), anesthetized with isoflurane in a
      chamber, were packed in ice and cooled until rectal temperatures decreased to
      approximately 30 degrees C. An intraaortic injection of heparinized saline at 4
      degrees C further cooled the brain to approximately 18 degrees C. Slices were
      obtained and then recovered at 37 degrees C in oxygenated medium. Interleaved
      31P/1H NMR spectra were acquired continually before, during, and after 20 min of
      no-flow hypoxia (PO2 approximately 0 mmHg). Histologic (Nissl stain) measurements
      were made from random slices removed at different times in the protocol. Three
      types of pretreatment were compared in no-flow hypoxia studies. The treatments
      were: (1) hyperoxia; (2) hypercapnia (50% CO2); and (3) hypoxia, which was
      accomplished by washing the slices with perfusate equilibrated with 100% N2 and
      maintaining a 100% N2 gas flow in the air space above the perfusate. RESULTS:
      During hyperoxia, 31P NMR metabolite ratios were identical to those seen in vivo
      in adult brains, except that, in vitro, the Pi peak was slightly larger than in
      vivo. A lactate peak was seen in in vitro 1H spectra of slices after metabolic
      recovery from decapitation, although lactate is barely detectable in vivo in
      healthy brains. The in vitro lactate peak was attributed to a small population of
      metabolically impaired cells in an injury layer at the cut edge. NMR spectral
      resolution from the solenoidal coil exceeded that obtained in vivo in surface
      coil experiments. Phosphocreatine and ATP became undetectable during oxygen
      deprivation, which also caused a three- to sixfold increase in the ratio of
      lactate to N-acetyl-aspartate. Within experimental error, all metabolite
      concentrations except pHi recovered to control values within 2 h after oxygen
      restoration. Nissl-stained sections suggested that pretreatment with hypercapnia
      protected neurons from cell swelling during the brief period of no-flow oxygen
      deprivation. CONCLUSIONS: Perfused, respiring adult brain slices having intact
      metabolic function can be obtained for NMR spectroscopy studies. Such studies
      have higher spectral resolution than can be obtained in vivo. During such NMR
      experiments, one can deliver drugs or molecular probes to brain cells and obtain
      brain tissue specimens for histologic and immunochemical measures of injury.
      Important ex vivo NMR spectroscopy studies that are difficult or impossible to
      perform in vivo are feasible in this model.

PMID- 8572334
TI  - Use of transesophageal atrial pacing during electroconvulsive therapy.

PMID- 8572335
TI  - Vertebral osteomyelitis as a cause of back pain after epidural anesthesia.

PMID- 8572336
TI  - Illicit cocaine ingestion during anesthesia.

PMID- 8572337
TI  - Coronary artery spasm after ephedrine in a patient with high spinal anesthesia.

PMID- 8572338
TI  - Propofol and postoperative pancreatitis.

PMID- 8572339
TI  - Spinal cord infarction after surgery in a patient in the hyperlordotic position.

PMID- 8572340
TI  - Effects of combining propofol and alfentanil on ventilation, analgesia, sedation,
      and emesis in human volunteers.
AB  - BACKGROUND: Propofol and alfentanil frequently are administered together for
      intravenous sedation. This study investigated pharmacokinetic and pharmacodynamic
      interactions between propofol and alfentanil, at sedative concentrations, with
      specific regard to effects on ventilation, analgesia, sedation, and nausea.
      METHODS: Ten male volunteers underwent steady-state infusions on 3 separate days
      consisting of propofol alone, alfentanil alone, or a combination of the two.
      Target plasma concentrations for propofol were 150, 300, and 600 ng/ml for 1 h at
      each concentration; for alfentanil it was 40 ng/ml for 3 h. Assessment included
      serial measurements of (1) ventilatory function (minute ventilation, carbon
      dioxide production, end-tidal carbon dioxide, ventilatory response to rebreathing
      7% CO2); (2) analgesia (subjective pain report in response to graded finger shock
      and evoked potential amplitude); (3) sedation (subjective rating, observer
      scores, and digit symbol substitution test); (4) nausea (visual analog scale, 0
      100 mm). RESULTS: During combination treatment, propofol plasma concentration was
      22% greater than during propofol alone using replicate infusion schemes (P <
      0.009). End-tidal carbon dioxide was unchanged by propofol, and increased equally
      by alfentanil and alfentanil/propofol combined (delta end-tidal carbon dioxide
      7.5 and 6.2 mmHg, respectively). Analgesia with propofol/alfentanil combined was
      greater than with alfentanil alone. (Pain report decreased 50% by PA vs. 28% for
      alfentanil, P < 0.05). Sedation was greater with propofol/alfentanil combined
      than with alfentanil or propofol alone (digit symbol substitution test 30 for
      propofol/alfentanil combined vs. 57 for alfentanil, and 46 for propofol, P <
      0.05). Nausea occurred in 50% of subjects during alfentanil, but in none during
      propofol/alfentanil combination treatment. CONCLUSIONS: The combination of
      propofol and alfentanil produced greater sedation and analgesia than that with
      either drug alone. Propofol offset the emetic effects of alfentanil. Equivalent
      depression of the carbon dioxide response curve, and elevation of end-tidal
      carbon dioxide occurred with propofol/alfentanil combined and alfentanil.

PMID- 8572341
TI  - Mortality during transjugular intrahepatic portosystemic shunt placement.

PMID- 8572342
TI  - Anaphylactoid reaction to protamine confirmed by plasma tryptase in a diabetic
      patient during open heart surgery.

PMID- 8572343
TI  - Pancreatitis after propofol administration: is there a relationship?

PMID- 8572344
TI  - Payment for routine postoperative patient-controlled analgesia.

PMID- 8572345
TI  - Preoxygenation technique is not ideal.

PMID- 8572346
TI  - Placement of an endotracheal device via the laryngeal mask airway in a patient
      with tracheal stenosis.

PMID- 8572347
TI  - Electrocardiogram ordering practices among anesthesiologists.

PMID- 8572348
TI  - Unrecognized migration of an entire guidewire on insertion of a central venous
      catheter into the cardiovascular system.

PMID- 8572349
TI  - Problems in assessing the effect of nebulized prostacyclin in patients whose
      lungs are ventilated.

PMID- 8572350
TI  - Presence of tumor necrosis factor alpha and tumor necrosis factor soluble
      receptors in erythrocyte concentrates.

PMID- 8572351
TI  - Horizons in Pain Research. San Diego, California, May 19-21, 1995.

PMID- 8572352
TI  - Cardiac outcome after peripheral vascular surgery. Comparison of general and
      regional anesthesia.
AB  - BACKGROUND: Despite evidence that regional anesthesia may be associated with
      fewer perioperative complications than general anesthesia, most studies that have
      compared cardiac outcome after general or regional anesthesia alone have not
      shown major differences. This study examines the impact of anesthetic choice on
      cardiac outcome in patients undergoing peripheral vascular surgery who have a
      high likelihood of associated coronary artery disease. METHODS: Four hundred
      twenty-three patients, between 1988 and 1991, were randomly assigned to receive
      general (n = 138), epidural (n = 149), or spinal anesthesia (n = 136) for femoral
      to distal artery bypass surgery. All patients were monitored with radial artery
      and pulmonary artery catheters. Postoperatively, patients were in a monitored
      setting for 48-72 h and had daily electrocardiograms for 4-5 days and creatine
      phosphokinase/isoenzymes every 8 h x 3, then daily for 4 days. Cardiac outcomes
      recorded were myocardial infarction, angina, and congestive heart failure.
      RESULTS: Baseline clinical characteristics were not different between anesthetic
      groups. Overall, the patient population included 86% who were diabetic, 69% with
      hypertension, 36% with a history of a prior myocardial infarction, and 41% with a
      history of smoking. Cardiovascular morbidity and overall mortality were not
      significantly different between groups when analyzed by either intention to treat
      or type of anesthesia received. In the intention to treat analysis, incidences of
      cardiac event or death for general, spinal, and epidural groups were 16.7%,
      21.3%, and 15.4%, respectively. The absolute risk difference observed between
      general and all regional anesthesia groups for cardiac event or death was -1.6%
      (95% confidence interval -9.2%, 6.1%) This reflected a nonsignificant trend for
      lower risk of postoperative events with general anesthesia. CONCLUSIONS: The
      choice of anesthesia, when delivered as described, does not significantly
      influence cardiac morbidity and overall mortality in patients undergoing
      peripheral vascular surgery.

PMID- 8572353
TI  - Measuring the performance of anesthetic depth indicators.
AB  - BACKGROUND: An appropriate measure of performance is needed to identify
      anesthetic depth indicators that are promising for use in clinical monitoring. To
      avoid misleading results, the measure must take into account both desired
      indicator performance and the nature of available performance data. Ideally,
      anesthetic depth indicator value should correlate perfectly with anesthetic depth
      along a lighter-deeper anesthesia continuum. Experimentally, however, a candidate
      anesthetic depth indicator is judged against a "gold standard" indicator that
      provides only quantal observations of anesthetic depth. The standard anesthetic
      depth indicator is the patient's response to a specified stimulus. The resulting
      observed anesthetic depth scale may consist only of patient "response" versus "no
      response," or it may have multiple levels. The measurement scales for both the
      candidate anesthetic depth indicator and observed anesthetic depth are no more
      than ordinal; that is, only the relative rankings of values on these scales are
      meaningful. METHODS: Criteria were established for a measure of anesthetic depth
      indicator performance and the performance measure that best met these criteria
      was found. RESULTS: The performance measure recommended by the authors is
      prediction probability PK, a rescaled variant of Kim's dy.x measure of
      association. This performance measure shows the correlation between anesthetic
      depth indicator value and observed anesthetic depth, taking into account both
      desired performance and the limitations of the data. Prediction probability has a
      value of 1 when the indicator predicts observed anesthetic depth perfectly, and a
      value of 0.5 when the indicator predicts no better than a 50:50 chance.
      Prediction probability avoids the shortcomings of other measures. For example, as
      a nonparametric measure, PK is independent of scale units and does not require
      knowledge of underlying distributions or efforts to linearize or to otherwise
      transform scales. Furthermore, PK can be computed for any degree of coarseness or
      fineness of the scales for anesthetic depth indicator value and observed
      anesthetic depth; thus, PK fully uses the available data without imposing
      additional arbitrary constraints, such as the dichotomization of either scale.
      And finally, PK can be used to perform both grouped- and paired-data statistical
      comparisons of anesthetic depth indicator performance. Data for comparing depth
      indicators, however, must be gathered via the same response-to-stimulus test
      procedure and over the same distribution of anesthetic depths. CONCLUSIONS:
      Prediction probability PK is an appropriate measure for evaluating and comparing
      the performance of anesthetic depth indicators.

PMID- 8572354
TI  - Prediction of movement during propofol/nitrous oxide anesthesia. Performance of
      concentration, electroencephalographic, pupillary, and hemodynamic indicators.
AB  - BACKGROUND: Movement in response to painful stimulation is the end point
      classically used to assess the potency of anesthetic agents. In this study, the
      ability of modeled propofol effect-site concentration to predict movement in
      volunteers during propofol/nitrous oxide anesthesia was tested, then it was
      compared with the predictive abilities of the Bispectral Index and 95% spectral
      edge frequency of the electroencephalogram, pupillary reflex amplitude, and
      systolic arterial blood pressure. In addition, the relationships between simple
      end points of loss and recovery of consciousness, and pupillary, hemodynamic, and
      propofol concentration indicators were studied. METHODS: Ten healthy volunteers
      were anesthetized with an infusion of propofol, which was increased in three
      equal steps to 21 mg.kg lean body mass-1.h-1. After loss of the ability to hold a
      syringe and of the eyelash reflex, 60% nitrous oxide was introduced and the
      trachea was intubated without the use of muscle relaxants. The propofol infusion
      rate then was decreased to 15.4 mg.kg lean body mass-1.h-1. Ten minutes later,
      tetanic electrical stimulation was administered to the thigh via needle
      electrodes: if movement was observed within 1 min, the propofol infusion rate was
      increased by 1.75 mg.kg lean body mass-1.h-1 5 min after the stimulus; if not, it
      was similarly decreased. This 15-min sequence was repeated until volunteers
      "crossed over" from movement to no movement (or vice versa) four times. The
      propofol infusion rate then was increased to 21 mg.kg lean body mass-1.h-1,
      nitrous oxide was discontinued, the trachea was extubated, and the infusion rate
      was decreased in five equal steps over 50 min. The times at which the eyelash
      reflex returned and the birth date was recalled were recorded. The
      electroencephalogram was monitored continuously (FP1, FP2, ref: nasion, ground:
      mastoid). Measurements of the pupillary response, arterial blood pressure, and
      heart rate were recorded during induction and awakening, just before and for 5
      min after each stimulation. Arterial blood samples were obtained for propofol
      assay, and propofol effect-site concentrations were calculated at each time. The
      predictive value of indicators was compared using a new static, the prediction
      probability (PK). RESULTS: Loss and return of the eyelash reflex occurred at
      greater propofol effect-site concentrations than either dropping the syringe or
      recall of the birthday. The propofol effect-site concentration (in the presence
      of 60% nitrous oxide) predicted to prevent movement after a supramaximal stimulus
      in 50% of volunteers was 1.80 micrograms/ml (95% confidence limits: 1.40-2.34
      micrograms/ml). The Bispectral Index (PK = 0.86), 95% spectral edge frequency (PK
      = 0.81), pupillary reflex amplitude (PK = 0.74), and systolic arterial blood
      pressure (PK = 0.78) did not differ significantly from modeled propofol effect
      site concentration (PK = 0.76) in their ability to predict movement. CONCLUSIONS:
      Indicators of pharmacodynamic effect, such as the electroencephalogram, pupillary
      light reflex, and systolic arterial blood pressure, predict movement as well as
      effect-site concentration during propofol/nitrous oxide anesthesia. Loss and
      return of the eyelash reflex correspond to a deeper level of anesthesia than
      syringe-dropping or recall of the birth date.

PMID- 8572355
TI  - Electroencephalogram bispectral analysis predicts the depth of midazolam-induced
      sedation.
AB  - BACKGROUND: The electroencephalogram (EEG) has been used to study the effects of
      anesthetic and analgesic drugs on central nervous system function. A prospective
      study was designed to evaluate the accuracy of various EEG parameters for
      assessing midazolam-induced sedation during regional anesthesia. METHODS: Twenty
      six consenting adult patients were administered 4.5-20 mg intravenous midazolam
      (in increments of 0.5-1 mg bolus doses every 6-10 min) until they became
      unresponsive to tactile stimulation (i.e., mild prodding or shaking). The EEG was
      continuously recorded from a bifrontal montage (FP1-Cz and FP2-Cz) to obtain the
      bispectral index (BI), 95% spectral edge frequency (SEF), median frequency (MF),
      and delta, theta, alpha, and beta power bands. Sedation was assessed clinically
      at 6-10-min intervals using the Observers' Assessment of Alertness/Sedation
      (OAA/S) scale, with 1 = no response (unconsciousness) to tactile stimulation to 5
      = wide awake. The EEG parameters were correlated with the OAA/S scores using
      nonparametric Spearman's rank-correlation analysis. Kruskal-Wallis analysis of
      variance was used to determine significant changes in EEG parameters during the
      onset of and recovery from midazolam-induced sedation. RESULTS: Of the EEG
      parameters studied, the BI exhibited the best correlation with OAA/S scores
      during both the onset (Spearman's Rho = 0.815) and recovery (Spearman's Rho =
      0.596) phases. With increasing sedation, there was a progressive decrease in the
      BI (OAA/S score of 5: BI = 95.4 +/- 2.3; 4: 90.3 +/- 4.5; 3:86.6 +/- 4.6; 2:75.6
      +/- 9.7; 1:69.2 +/- 13.9). A similar pattern was found for the 95% SEF as the
      OAA/S score decreased from 4 to 1. Similarly, EEG-BI increased with recovery from
      the sedative effects of midazolam (OAA/S score = 2:BI = 75.2 +/- 10.2; 3:82.3 +/-
      7.3; 4:90.8 +/- 6). However, no consistent changes were found with the other EEG
      parameters. The mean EEG values between OAA/S scores 3 and 2 and between OAA/S
      scores 2 and 1 during the onset and recovery phases from midazolam-induced
      sedation, defined as EEG50 values for response to verbal command (EEG50-VC) and
      to shaking of the head (EEG50-SH), were 79.3 +/- 8 and 70.8 +/- 14.3,
      respectively, for EEG-BI. The EEG-BI displayed the smallest coefficients of
      variation for the EEG50-VC and EEG50-SH values. CONCLUSIONS: The EEG-BI appears
      to be a useful parameter for assessing midazolam-induced sedation and can predict
      the likelihood of a patient responding to verbal commands or to shaking of the
      head during midazolam-induced sedation.

PMID- 8572356
TI  - Differences in respiratory reflex responses from the larynx, trachea, and bronchi
      in anesthetized female subjects.
AB  - BACKGROUND: Animal studies show that airway receptors responsible for eliciting
      respiratory protective reflexes are not uniformly distributed in the airways.
      Based on this information, it is possible that the protective reflex responses to
      airway irritation in humans may vary, depending on the site of stimulation. The
      purpose of this study is to examine whether the protective reflex responses
      evoked from the larynx are different from those evoked from the lower airways and
      to see how change in depth of anesthesia modifies the protective reflex responses
      evoked from individual sites. METHODS: The airway mucosa of the larynx, tracheal
      carina, and bronchi were stimulated by injection of distilled water (0.5 ml) at
      two different depths of sevoflurane anesthesia (1.2 and 1.8 MAC) in 11 female
      subjects breathing spontaneously through the laryngeal mask airway. The
      respiratory responses were monitored by measuring ventilatory flow and airway
      pressure. RESULTS: At 1.2 MAC of sevoflurane anesthesia, both laryngeal and
      tracheal stimulation caused protective responses, such as forceful expiratory
      efforts, apnea, and spasmodic panting, whereas bronchial stimulation caused
      little or no such responses. There was no significant difference in the incidence
      of different types of reflex responses between the larynx and the trachea. At 1.8
      MAC of sevoflurane, the nature of the elicited responses was very similar to that
      observed at 1.2 MAC of sevoflurane, showing little dose-dependence of anesthetic
      effect. CONCLUSIONS: The respiratory reflex responses evoked by injection of
      water vary, depending on the site of stimulation. The incidence of various reflex
      responses was not affected by the changing depth of anesthesia. The sensitivity
      to airway irritation seems to be greater at the larynx and trachea than at the
      more peripheral airways.

PMID- 8572357
TI  - Propofol fails to attenuate the cardiovascular response to rapid increases in
      desflurane concentration.
AB  - BACKGROUND: A rapid increase in desflurane concentration to greater than 1 MAC
      transiently increases heart rate, arterial blood pressure, and circulating
      catecholamine concentration. Because propofol decreases sympathetic outflow, it
      was hypothesized that propofol would blunt these responses. METHODS: To test this
      hypothesis, five healthy male volunteers were studied three times. After
      induction of anesthesia with 2 mg.kg-1 propofol, anesthesia was maintained with
      4% end-tidal desflurane in oxygen (0.55 MAC) via an endotracheal tube for 32 min.
      On separate occasions, in random order, either no propofol or 2 mg.kg-1 propofol
      was administered either 2 or 5 min before increasing end-tidal desflurane
      concentration from 4% to 8%. RESULTS: Without propofol pretreatment, the increase
      to 8% desflurane transiently increased heart rate (from 63 +/- 3 beats/min to 108
      +/- 5 beats/min, mean +/- SEM; P < 0.01), mean arterial pressure (from 73 +/- 1
      mmHg to 118 +/- 6 mmHg; P < 0.01), and epinephrine concentration (from 14 +/- 1
      pg.ml-1 to 279 +/- 51 pg.ml-1; P < 0.05). There was no significant change in
      norepinephrine concentration (from 198 +/- 37 pg.ml-1 to 277 +/- 46 pg.ml-1). The
      peak plasma epinephrine concentration was attenuated by each propofol
      pretreatment (158 +/- 35 pg.ml-1, propofol given 2 min before, and 146 + 41 pg.ml
      1, propofol given 5 min before; P < 0.05), but neither propofol pretreatment
      modified the cardiovascular or norepinephrine responses. CONCLUSIONS: Although
      able to blunt the increase in epinephrine concentration, propofol 2 mg.kg-1
      propofol does no attenuate the transient cardiovascular response to a rapid
      increase in desflurane concentration to greater than 1 MAC.

PMID- 8572358
TI  - Hemodynamic responses to intravascular injection of epinephrine-containing
      epidural test doses in adults during general anesthesia.
AB  - BACKGROUND: Epidural anesthesia is sometimes initiated during general anesthesia,
      yet few data exist concerning efficacy of epinephrine-containing test doses.
      METHODS: Thirty-six patients were randomized to receive either 0.5 MAC
      isoflurane, 1 MAC isoflurane, or 0.5 MAC each (1 MAC total) of isoflurane and
      nitrous oxide. Each subject received intravenous saline followed by three test
      doses containing 45 mg lidocaine with 7.5, 15, and 30 micrograms epinephrine in a
      randomized, double-blind fashion. Heart rate and systolic, diastolic, and mean
      blood pressures were measured for 5 min after injection. Positive hemodynamic
      criteria identifying intravascular injection were determined from peak increases
      in hemodynamics during administration of saline. Dose-effect relationships
      between epinephrine and peak increases in hemodynamics were assessed with linear
      regression. Minimum required doses of epinephrine to produce peak positive
      hemodynamic increases on average were determined from linear regression. RESULTS:
      Positive hemodynamic criteria were identified as increases in heart rate > or = 8
      beats/min, systolic blood pressure > or = 13 mmHg, diastolic blood pressure > or
      = 7 mmHg, and mean blood pressure > or = 9 mmHg. Significant dose-effect
      relationships were observed for epinephrine and peak increases in hemodynamics
      (correlation coefficients ranged from 0.61-0.91). Minimum required doses of
      epinephrine ranged from 6 to 19 micrograms depending on hemodynamic measurement
      and anesthetic group. CONCLUSIONS: Hemodynamic responses to intravascular
      injection of test doses vary with dose of epinephrine and depth and type of
      general anesthetic used. Thus, the 15 micrograms epinephrine contained in the
      standard test dose may not be sufficient during all anesthetic conditions.

PMID- 8572359
TI  - Prospective examination of epidural catheter insertion.
AB  - BACKGROUND: Although it is generally accepted that inserting epidural catheters 3
      4 cm into the epidural space minimizes complications, no prospective randomized
      examination of epidural catheter insertion length has been published. METHODS:
      Eight hundred healthy parturients requesting epidural analgesia were randomized
      to have open-tip epidural catheters inserted 2, 4, 6, or 8 cm within the epidural
      space. The incidences of intravenous cannulation, unilateral sensory analgesia,
      and subsequent catheter dislodgment were recorded. Catheter insertions that
      resulted in intravenous cannulation or unilateral analgesia were incrementally
      withdrawn and retested with additional local anesthetic to determine the
      effectiveness of epidural catheter manipulation. RESULTS: Epidural catheters
      inserted 8 cm within the epidural space were more likely to result in intravenous
      cannulation. Epidural catheters inserted 2 cm within the epidural space were less
      likely to result in unilateral sensory analgesia but were more likely to become
      dislodged. Twenty-three percent of epidural catheters inserted > 2 cm within the
      epidural space required manipulation. Epidural catheters inserted 2 or 4 cm
      required replacement more often than epidural catheters inserted 6 or 8 cm.
      Ninety-one percent and 50% of epidural catheters that resulted in unilateral
      sensory analgesia and intravenous cannulation, respectively, provided analgesia
      for labor and delivery after incremental withdrawal. CONCLUSIONS: Epidural
      catheters should be inserted either 2 cm when rapid labor is anticipated or 6 cm
      when prolonged labor or cesarean delivery is likely. Additionally, epidural
      catheters that result in intravenous cannulation or unilateral sensory analgesia
      can be manipulated effectively to provide analgesia for labor and delivery.

PMID- 8572360
TI  - Comparison of the spinal actions of the mu-opioid remifentanil with alfentanil
      and morphine in the rat.
AB  - BACKGROUND: mu-Opioids administered spinally produce a potent, dose-dependent
      analgesic response in preclinical and clinical investigations. Side-effect
      profile of these compounds may be altered as a function of pharmacokinetics. The
      effects of intrathecal and intraperitoneal remifentanil, an esterase-metabolized
      mu opioid, alfentanil, and morphine were compared. METHODS: Intrathecal and
      intraperitoneal remifentanil, alfentanil, and morphine were examined in rats
      tested for hind-paw thermal withdrawal latency. The antinociceptive response was
      assessed and in parallel a scoring of four different parameters summarized as a
      supraspinal index to assess supraspinal side-effect profiles after the several
      drugs were delivered by the different routes. RESULTS: All opioids produced a
      dose-dependent analgesic response after intrathecal administration. The ordering
      of potency (intrathecal ED50 in micrograms) was remifentanil (0.7) > morphine
      (12.0) > alfentanil (16.3) > GR90291, principal remifentanil metabolite (> 810
      micrograms). Time until onset of analgesia after intrathecal or intraperitoneal
      delivery was morphine > remifentanil = alfentanil. When matched for analgesic
      effect, the relative duration of action was morphine >> alfentanil >
      remifentanil. The supraspinal index showed a dose-dependent increase for all
      agents. All intraperitoneal drugs showed dose-dependent increases in
      antinociception with potency (intraperitoneal ED50 in micrograms) of remifentanil
      (4.3) > alfentanil (24.4) > morphine (262). Calculation of intrathecal or
      intraperitoneal ratios for supraspinal side effects/analgesia (supraspinal index
      ED50/analgesia ED50) revealed remifentanil to be greatest when intrathecally
      administered: remifentanil (4 intrathecal: 1.4 intraperitoneal); alfentanil (0.7
      intrathecal: 1.5 intraperitoneal); and morphine (1 intrathecal: 5.6
      intraperitoneal). CONCLUSIONS: These observations indicate that remifentanil has
      a powerful spinal opioid action. Consistent with its lipid-solubility, it has an
      early onset like alfentanil but displays a shorter duration of action after bolus
      delivery. Despite lipid solubility, remifentanil has a significant spinal
      therapeutic ratio. These observations likely reflect the rapid inactivation of
      systemically redistributed agent by plasma esterases.

PMID- 8572361
TI  - First international workshop on porcine chromosome 6. Report and abstracts.
AB  - Recent advances in the use of microsatellite markers and the development of
      comparative gene mapping techniques have made the construction of high resolution
      genetic maps of livestock species possible. Framework and comprehensive genetic
      linkage maps of porcine chromosome 6 have resulted from the first international
      effort to integrate genetic maps from multiple laboratories. Eleven highly
      polymorphic genetic markers were exchanged and mapped by four independent
      laboratories on a total of 583 animals derived from four reference populations.
      The chromosome 6 framework map consists of 10 markers ordered with high local
      support. The average marker interval of the framework map is 15.1 cM (sex
      averaged). The framework map is 135, 175 and 109 cM in length (for sex averaged,
      female and male maps, respectively). The comprehensive map includes a total of 48
      type I and type II markers with a sex averaged interval of 3.5 cM and is 166, 196
      and 126 cM (for sex averaged, female and male maps, respectively). Additional
      markers within framework map marker intervals can thus be selected from the
      comprehensive map for further analysis of quantitive trait loci (QTL) located on
      chromosome 6. The resulting maps of swine chromosome 6 provide a valuable tool
      for analysing and locating QTL.

PMID- 8572362
TI  - Survey on swine SINEs (PRE-1) as candidates for SSCP markers in genetic linkage
      analysis.
AB  - Of 310 random cosmid clones, 216 were positive for PRE-1 sequences by Southern
      hybridization. Thirty nine sub-fragments positive for the PRE-1 sequences were
      cloned from independent cosmid clones, and sequenced, with 17 complete PRE-1
      elements found. Seven PRE-1 loci were amplified by polymerase chain reaction
      using genomic DNA of 12 unrelated pigs as template. The amplified fragments were
      then subjected to an analysis of single strand conformation polymorphism, with
      all the loci being polymorphic.

PMID- 8572363
TI  - Mutations in the equine plasma transferrin and esterase systems.
AB  - Eleven apparent mutations of the equine plasma transferrin and esterase gene (10
      in TF and one in ES) were found in an analysis of approximately 240,000
      thoroughbred horses. Eight of the transferrin mutations produced variants not
      previously recognized in horses. In the two remaining transferrin mutations and
      the esterase mutation, reduced plasma concentrations of the proteins were
      demonstrated by immunological techniques and together with the family data
      indicated the existence of 'null' alleles.

PMID- 8572364
TI  - Identification and characterization of new BoLA-DRB3 alleles by heteroduplex
      analysis and direct sequencing.
AB  - A sample of 52 mixed-breed dairy cattle (Holstein Friesian and Jersey) and 51
      beef cattle (Hereford) from south-east Queensland was studied. The second exon of
      BoLA-DRB3 was amplified by polymerase chain reaction (PCR), and polymorphisms
      were detected by heteroduplex analysis. A large number of different heteroduplex
      patterns indicated extensive sequence polymorphism. Direct sequencing of PCR
      products from 17 homozygotes and cloning and sequencing of PCR product from two
      heterozygotes resulted in the identification and characterization of four novel
      alleles. The previously described allele BoLA-DRB3*2A is characterized by an
      amino acid deletion at position 65. We have identified three animals that are
      homozygous for this amino acid deletion, indicating that the deletion is unlikely
      to result in loss of function. Two of these animals had allele BoLA-DRB3*2A, and
      one had a novel allele with codon 65 deleted but differing from BoLA-DRB3*2A at a
      number of other amino acid positions. In conclusion, heteroduplex analysis allows
      rapid discrimination between homozygotes and heterozygotes, and enables rapid
      identification of new BoLA-DRB3 alleles.

PMID- 8572365
TI  - Casein haplotypes and their association with milk production traits in the
      Finnish Ayrshire cattle.
AB  - Polymorphism of casein genes was studied in half-sib families of artificial
      insemination bulls of the Finnish Ayrshire dairy breed. Ten grandsires and 300 of
      their sons were genotyped for the following polymorphisms: alpha s1-casein (B,
      C), beta-casein (A1, A2), the microsatellite within the kappa-casein gene (ms5,
      ms4) and kappa-casein (A, B, E). Nine different combinations of these alleles,
      casein haplotypes, were found. Associations between casein haplotypes and milk
      production traits (milk and protein yield, fat and protein percentage and milking
      speed) were studied with ordinary least-squares analysis to find a direct effect
      of the haplotypes or an association within individual grandsire families using
      the granddaughter design. Estimated breeding values of sons were obtained from
      cow evaluation by animal model. No direct effect of the casein haplotypes on the
      traits was found. Within grandsire families, in one out of four families the
      chromosomal segment characterized by haplotype 3 (B-A2-ms4-A) was associated with
      an increase in milk yield (P < 0.01) and a decrease in fat percentage (P < 0.01)
      when contrasted with haplotype 8 (B-A1-ms4-E). The results provide evidence that
      in the Finnish Ayrshire breed at least one quantitative trait locus affecting the
      genetic variation in yields traits is segregating linked to either haplotype 3 (B
      A2-ms4-A) or 8 (B-A1-ms4-E).

PMID- 8572367
TI  - Genetic control of PI and GC variants in the American mink.
AB  - Genetic polymorphism of the serum alpha-protease inhibitor (PI) and group
      specific component (GC) in minks was revealed using one-dimensional
      polyacrylamide gel electrophoresis and immunoblotting. Two codominant alleles
      were identified at each of the two loci. The data ruled out the possibility of
      any linkage between the PI, GC and the coat colour gene Crystal (Cr).

PMID- 8572366
TI  - Genetic variation in domestic reindeer and wild caribou in Alaska.
AB  - Reindeer (Rangifer tarandus tarandus) were introduced into Alaska 100 years ago
      and have been maintained as semidomestic livestock. They have had contact with
      wild caribou (R.t.granti) herds, including deliberate crossbreeding and mixing in
      the wild. Reindeer have considerable potential as a domestic animal for meat or
      velvet antler production, and wild caribou are important to subsistence and sport
      hunters. Our objective was to quantify the genetic relationships of reindeer and
      caribou in Alaska. We identified allelic variation among five herds of wild
      caribou and three herds of reindeer with DNA sequencing and restriction enzymes
      for three loci: a DQA locus of the major histocompatibility complex (Rata-DQA1),
      kappa-casein and the D-loop of mitochondrial DNA. These loci are of interest
      because of their potential influence on domestic animal performance and the
      fitness of wild populations. There is considerable genetic variation in reindeer
      and caribou for all three loci, including five, three and six alleles for DQA,
      kappa-casein and D-loop respectively. Most alleles occur in both reindeer and
      caribou, which may be the result of recent common ancestry or genetic
      introgression in either direction. However, allele frequencies differ
      considerably between reindeer and caribou, which suggests that gene flow has been
      limited.

PMID- 8572368
TI  - Prediction of informativeness for microsatellite markers among progeny of sires
      used for detection of economic trait loci in dairy cattle.
AB  - Individual loci affecting economic traits can be located using genetic linkage.
      Application of either daughter or granddaughter design requires determination of
      allele origin in the progeny. If only the sires and their progeny are genotyped,
      the paternal allele origin of progeny having the same genotype as the sire cannot
      be determined. The expected frequency of informative sons can be predicted for
      each sire and genetic marker from the allele frequencies in the population. The
      accuracy of a predictor of the frequency of informative progeny was tested on 103
      grandsire x microsatellite combinations. Number of sons per grandsire varied from
      24 to 129. Allele frequencies in the population were estimated by genotyping
      seven sires. The regression of the frequency of informative sons on the predicted
      frequency was 1.04 with a zero intercept model. Thus, considering the large
      number of genetic markers available for analysis, predicted informative frequency
      is a useful criterion for selection of genetic markers.

PMID- 8572370
TI  - A bovine Y-specific marker amplified by RAPD.

PMID- 8572369
TI  - Ten novel chicken dinucleotide repeat polymorphisms.

PMID- 8572371
TI  - PCR/RFLP markers in the canine gamma-D-crystallin gene.

PMID- 8572372
TI  - A TaqI polymorphism at the porcine arachidonate 12-lipoxygenase (ALOX12) locus.

PMID- 8572373
TI  - A polymorphic bovine dinucleotide repeat D12S25 (IOBT323) at chromosome 12q24.

PMID- 8572374
TI  - Five bovine polymorphic dinucleotide microsatellite loci (DIK008, DIK010, DIK015,
      DIK016 and DIK020).

PMID- 8572375
TI  - Five bovine polymorphic dinucleotide microsatellite loci (DIK021, DIK023, DIK024,
      DIK026 and DIK028).

PMID- 8572376
TI  - Caprine microsatellite dinucleotide repeat polymorphisms at the SR-CRSP-11, SR
      CRSP-12, SR-CRSP-13, SR-CRSP-14 and SR-CRSP-15 loci.

PMID- 8572377
TI  - [Respective value of glycated hemoglobin and fructosamine assays in the care of
      diabetes mellitus].
AB  - The monitoring of metabolic balance in diabetes mellitus involves the assay of
      cumulative markers of protein glycation. Glycated hemoglobin, particularly the
      major component HbA1c, and fructosamine, which reflects glycated plasma protein
      levels, are the most commonly used parameters. Nevertheless, their utilization is
      still under discussion with respect to methodologies used, as well as to their
      respective interest in clinical diabetology. This review shows current opinion
      concerning the analytical and physiopathological use of these biological
      indicators.

PMID- 8572378
TI  - [Measurement of biological parameters of endothelial origin: value in human
      pathology].
AB  - Endothelial damage is a major factor in the pathogenesis of vascular diseases,
      but routine investigations of vascular lesions are hampered due to endothelial
      cell characteristics such as limited accessibility, intrinsic immunological and
      functional heterogeneity as well as the lack of specific markers. The most
      frequently used markers are soluble substances, found in plasma, such as the von
      Willebrand factor, thrombomodulin, tissue plasminogen activator and its
      inhibitor, or soluble adhesion molecules. Their easy evaluation in semi-routine
      tests gives access to a global exploration of functional alterations and of
      abnormal states of endothelial activation. Immunohistological techniques using
      monoclonal antibodies allow to study the expression of membrane antigens and
      permit direct and specific investigation of activation states of endothelium.
      However, the invasive and traumatic characteristics of sampling procedure
      considerably limit the utilization of immunohistological techniques for clinical
      applications. Detection in the peripheral blood of endothelial cells detached
      from vessels could be a good marker for desquamative lesions. From a simple blood
      sample, it is now possible, using specific immunodetection techniques to isolate
      circulating endothelial cells present in low numbers in various pathologies
      associated with vascular injury. Although significant modifications of these
      markers have been found associated with endothelial alterations, prospective
      clinical studies are still necessary to demonstrate their clinical relevance in
      vascular diseases.

PMID- 8572379
TI  - [Rapid assay of plasma acetate by gas chromatography: evaluation and comparison
      with two other methods].
AB  - Human plasma acetate is derived from colonic fermentation of fiber and endogenous
      metabolism of dextrose and fatty acids. Acetate may have regulatory functions in
      hepatic carbohydrate metabolism. Intake of dietary fiber is associated with
      several beneficial effects on carbohydrates and lipids metabolisms. To study
      theses effects a valid and automated method for routine analysis of acetate in
      plasma is necessary. After oral administration of lactulose to healthy human
      volunteers, the concentration of plasma acetate was measured by head space gas
      chromatography (HS-GC), vacuum distillation gas chromatography (VD-GC) and
      enzymatic spectrometric method (ES). The method HS-GC was linear to 0.5 mmol.l-1
      (n = 5, r = 0.998), the detection limit is 0.005 mmol.l-1. Within-day variation
      (CV) was 3.60% and day-to-day variation was 4.5% (0.1 mmol.l-1). The coefficients
      of correlation between CG-ET/CG-DsV and CG-ET/E-M are 0.903 (p = 0.0001) and 0.54
      (p = 0.006) respectively, the mean square errors are respectively 0.118 and 0.138
      mmol.l-1. The variation curves of plasma acetate measured by GC versus time show
      peak concentration of 0.323 to 0.380 mmol.l-1 at 120 min.

PMID- 8572380
TI  - [Determination of serum or plasma alpha-tocopherol by high performance liquid
      chromatography: optimization of operative models].
AB  - A previous multicentric study set up by the Societe francaise de biologie
      clinique has emphasized the usefulness of a standardized procedure for the
      determination by high performance liquid chromatography of alpha-tocopherol in
      serum or plasma. In our study, we have tested every step of the different
      published procedures: internal standard adduct, lipoprotein denaturation and
      vitamin extraction. Reproducibility of results was improved by the use of tocol
      as an internal standard when compared to retinol or alpha-tocopherol acetates.
      Lipoprotein denaturation was more efficient with ethanol addition than with
      methanol and when the ethanol/water ratio was > or = 0.7. Use of n-hexane or n
      heptane gave the same recovery of alpha-tocopherol. When organic solvent/water
      ratio was > or = 1, n-hexane enabled to efficiently extract, in a one-step
      procedure, the alpha-tocopherol from both normo and hyperlipidemic sera.
      Performances of the selected procedure were: detection limit: 0.5 microM--linear
      range: 750 microM--within run coefficient of variation: 2.03%--day to day: 4.76%.
      Finally, this pluricentric study allows us to propose an optimised procedure for
      the determination of alpha-tocopherol in serum or plasma.

PMID- 8572381
TI  - [Variability of INR due to thromboplastin. Comparison of two recombinant
      thromboplastins and one rabbit thromboplastin].
AB  - We have compared the INR obtained with three different thromboplastin reagents:
      one rabbit and two recombinant tissue factor thromboplastins using the same
      coagulometer. A preliminary study has shown that freezing of plasmas at -80
      degrees centigrade causes a 6% increase in INR. We did this experiment on 57
      plasma samples from patients receiving oral anticoagulant therapy, none of them
      receiving heparin. Results show that global prothrombin activity expressed in
      percentage is significantly lower with recombinant tissue factors than with
      rabbit thromboplastin. ISI of one of the two recombinant thromboplastins did not
      seem to be appropriate to our coagulometer highpointing the variability of INR
      due to the coagulation analyzer. This underlines the necessity for each
      laboratory to assess the ISI value provided by the manufacturer according to its
      working conditions. This study suggests that the results of prothrombin time
      should be exclusively expressed in INR for patients treated with oral
      anticoagulants.

PMID- 8572382
TI  - [Interference observed in creatinine assays in peritoneal dialysis solutions
      containing amino-acids].

PMID- 8572383
TI  - Liver abscess caused by Haemophilus paraphrophilus and Streptococcus anginosus.

PMID- 8572384
TI  - Rapid, simple and sensitive identification of meprobamate in plasma or urine
      using Toxi-Tube-B zero from Toxi-Lab and colored reaction on filter paper.

PMID- 8572385
TI  - [Equipment safety and conditions of failure].

PMID- 8572386
TI  - [Aseptic meningitis. Demonstration of bacterial DNA in cerebrospinal fluid by
      gene amplification].
AB  - OBJECTIVE: To develop a diagnostic tool to recognize whether a postoperative
      meningitis occurring in neurosurgical patients is of bacteriological origin or
      not, in detecting in CSF bacterial DNA with the polymerase chain reaction (PCR)
      technique. STUDY DESIGN: Laboratory study. PATIENTS: Twenty-seven neurosurgical
      ICU patients associating, in the postoperative period, the CDC criteria of
      meningitis and a neutrophil polymorphonuclear count over 100 cells.mm-3 were
      allocated either into the MB+ group (n = 7) when their CSF culture was positive
      or in the MB- group (n = 20) when the culture was sterile. The CSF of 43
      neurosurgical ICU patients without postoperative clinical and biological features
      of meningitis acted as controls. Sixteen specimens out of the 43 were inoculated
      with bacteria at a known concentration. METHODS: The CSF specimens of all
      patients were tested for the presence of eurcaryote DNA using the PCR technique.
      Beforehand its sensitivity had been assessed using the inoculated CSF of control
      group: a positive amplification at 20 cycles was equivalent to 10(5) CFU.mL-1 and
      a positive amplification at 25 cycles to 10(3) CFU.mL-1. RESULTS: In the 43
      sterile control CSF specimens the amplification was negative in all at 20 cycles
      and in 42 at 25 cycles. In the 16 previously sterile control specimens
      supplemented with bacteria, as well as in the CSF of all 7 patients of MB+ group
      the amplification was positive at 20 and 25 cycles. In those of MB- group the
      amplification was negative in all at 20 cycles, but was positive in 19 out of 20
      at 25 cycles. Southern blot with specific procaryote probes was positive with
      amplification products from CSF of MB+ and MB- groups and negative with control
      CSFs and human DNA. DISCUSSION: The presence of bacteria in CSF of patients
      sustaining a meningitis can be accurately detected through their DNA.
      Postoperative aseptic meningitides may have a bacterial origin. PCR can be used
      as a routine technique to provide a diagnosis of bacterial meningitis in less
      than 6 hours. Additionally specific oligonucleotides allow to identify the
      bacteria in less than 12 hours.

PMID- 8572387
TI  - [Combination of propofol-sufentanil on somatosensory evoked potentials in surgery
      of the spine].
AB  - OBJECTIVES: Most anaesthetics depress cortical somatosensory evoked potentials
      (CSEPs). However, the modification of CSEPs during total intravenous anaesthesia
      using propofol remaining still unknown, justified this trial. TYPE OF STUDY:
      Open, prospective, clinical study. METHODS: Nine consecutive patients requiring
      CSEPs monitoring for spine surgery, were studied. Anaesthesia was induced with
      propofol (2.5 mg.kg-1 then 10 mg.kg-1.h-1) and sufentanil (0.50 micrograms.kg-1
      then 0.25 micrograms.kg-1.h-1). Maximum positive (P40) and negative (N50)
      waweform latencies, and the peak to peak amplitude of CSEPs (posterior tibial
      nerve stimulation, cortical recording), were recorded before induction, 30 min, 1
      and 2 h after induction, and at the end of surgery. Data are means +/- SD.
      RESULTS: Duration of anaesthesia was 260 +/- 73 min. Propofol induced significant
      lengthening of CSEPS (P40: from 37 +/- 10 up to 41 +/- 11 ms; N50: from 45 +/- 11
      up to 51 +/- 14 ms), and a significant decrease in amplitude (from 1.9 +/- 0.9
      down to 0.8 +/- 0.4 microV), but these changes were stable from 30 min after the
      induction to the end of spine surgery. A motor response was obtained 29 +/- 14
      min after the end of anaesthetic administration. CONCLUSIONS: Total intravenous
      anaesthesia with propofol and sufentanil induces a small but stable lengthening
      of CSEPs latency and a stable decrease of its amplitude, which enable an
      appropriate monitoring of CSEPs during spine surgery.

PMID- 8572388
TI  - [Muromonab CD3 (Orthoclone OKT3) for the prophylaxis of heart allograft
      rejection. Hemodynamics and respiratory tolerance].
AB  - OBJECTIVE: Treatment of transplant rejection with muromonab CD3 (Orthoclone OKT3)
      may result in haemodynamic instability and pulmonary oedema, which would question
      its prophylactic use. The aim of this study was to the evaluate haemodynamic and
      respiratory tolerance of prophylactic treatment of cardiac rejection with OKT3.
      STUDY DESIGN: Prospective clinical study. PATIENTS: Twelve patients, whose
      pulmonary arterial resistances before transplantation were less than 400 dyn.s.cm
      5, with haemodynamic and respiratory stability during the 4 hours before OKT3
      administration. METHOD: Patients under preventive haemodynamic support with
      isoprenaline 0.05 micrograms.kg-1.min-1 and dopamine 3 micrograms.kg-1.min-1.
      Immunosuppressive treatment with azathioprine 5 mg.kg-1 at d0 and 3 mg.kg-1 at d1
      and d2 and with methylprednisolone 720 mg at d0 and 240 mg at d1 and d2. OKT3, 5
      mg administered i.v. at d0, d1, d2. Respiratory and haemodynamic variables were
      recorded prior to (T0), 30 min (T1) and 360 min (T2) after injection of OKT3.
      RESULT: Neither clinical nor radiological changes were observed after the OKT3
      injections. At d0, T2, the heart rate increased and PaO2 and SaO2 decreased. At
      d1 and d2, T1, PaO2 decreased, and QS2QT at T1 d2 increased by nearly 3%.
      CONCLUSION: OKT3 does not result in major circulatory and haematosis changes,
      provided patients are selected, especially free of pretransplantation pulmonary
      hypertension. Prior to the treatment with OKT3, they should be in a satisfactory
      haemodynamic and respiratory status and receive high doses of corticosteroids.

PMID- 8572389
TI  - [Measurement of tympanic temperature by infrared and thermocouple thermometry. A
      comparative study].
AB  - OBJECTIVE: To compare tympanic temperatures obtained with an infrared thermometer
      Core Check 2090A (IVAC), non in contact with the tympanic membrane, to values
      obtained with a thermocouple thermometer Mon-A-Therm (Mallinckrodt) in contact
      with it, and to assess whether the differences depend on the person measuring the
      temperature. STUDY DESIGN: Prospective comparative open study. PATIENTS: The
      study included 150 adults in whom the tympanic temperatures were measured at
      their admission to recovery room by 10 nurse anaesthetists. METHODS: Each
      thermometer was inserted in the same patient into an external acoustic meatus.
      The median and range of the temperature differences were used to assess the bias
      and the accuracy of the measures. Their reliability was analyzed with
      consideration of the measuring person and the presence of irrelevant values,
      defined as a temperature difference over 0.3 degrees C. RESULTS: The temperatures
      obtained with both devices were similar (36.2 +/- 0.7 degrees C with IVAC
      thermometer vs 36.2 +/- 0.8 degrees C with Mallinckrodt thermometer). The median
      value of the differences was 0 degrees C, with a range of 2.5 degrees C (maximum
      value + 1.5 degrees C, minimum value: -1 degree C). Nineteen patients could be
      qualified as hypothermic (temperature < 36.5 degrees C) with one thermometer and
      normothermic (temperature > or = 36.5 degrees C) with the other. Among them, only
      9 (6%) had temperature differences above 0.3 degrees C. The temperature
      differences were not different according to the measuring nurse. Nevertheless two
      of them obtained major differences or irrelevant figures. CONCLUSIONS: As
      compared to the thermocouple thermometry, infrared thermometry has no bias but a
      low precision. The measurement error does not allow the recognition of
      hypothermia in 6% of patients. The error may be made by the measuring person
      and/or related to the anatomy and the patency of the external acoustic meatus.
      Tympanic infrared thermometry seems to be a convenient method for temperature
      measurements at short time intervals in the recovery room, provided its
      limitations are kept in mind.

PMID- 8572390
TI  - [Effects of anesthesia on postoperative micturition and urinary retention].
AB  - Postoperative micturition difficulties, considered as minor complications, have a
      high incidence. Acute urinary retention can follow all types of anaesthetics or
      operations. Surgical trauma to the pelvic nerves or to the bladder, postoperative
      oedema around the bladder neck, and pain-induced reflex spasm of the external and
      internal urethral sphincters may play a role in the development of urinary
      retention. Acute urinary retention is the most common complication of surgery for
      benign anorectal disease. The incidence of urinary retention is more likely to
      occur in old male patients. Preoperative urinary symptoms are not a prerequisite
      for developing postoperative urinary retention, although they are considered to
      be a risk factor. The type of anaesthetic, postoperative pain and its management
      may have little effect on the occurrence of postoperative urinary dysfunction.
      Studies on the urodynamic effects of various anaesthetic agents are rare. The
      parasympatholytic drugs increase bladder capacity, decrease the rate of bladder
      contractions and cause downward trends in urethral resistance. The barbiturates
      and halothane produce similar effects on urethral resistance. The anaesthetic
      agents decrease the intrabladder pressure and inhibit the micturition reflex.
      Halothane decreases bladder contractions and increases its capacity measured by
      the cystometrogram. Urinary retention is a side effect of opioids, particularly
      after intrathecal or epidural administration. Epidural morphine relaxes the
      detrusor muscle with a corresponding increase in the maximal bladder capacity.
      Spinal opioids influence the function of the lower urinary tract, by direct
      spinal action on the sacral nociceptive neurons and autonomic fibres, as well as
      by an effect on supraspinal centres. Naloxone increases detrusor pressure,
      decreases bladder capacity, and causes a need to void. Urinary retention is less
      common after a short-acting (lidocaine 5%) than after a long-acting agent
      (bupivacaine 0.5%). After spinal anaesthesia, detrusor strength and the ability
      to void restarts with the return of sacral sensation to pinprick. A single
      episode of bladder overdistention can result in significant morbidity.
      Overfilling of the bladder can stretch and damage the detrusor muscle, leading to
      atony of the bladder wall, so that recovery of micturition may not occur when the
      bladder is emptied. On the other hand, the excessive use of an indwelling
      catheter can lead to urinary tract infection, urethral stricture and prolonged
      hospital stay. Short-term prophylactic catheterisation is recommended in patients
      with obstructive symptoms. Patients at risk for urinary retention should be
      stimulated to void and provided a quiet environment in which to do so. They
      should be encouraged to seat, stand or ambulate as early as possible. The alpha 1
      adrenergic receptor blocking agents have been used for treatment of organic or
      functional urinary retention. It is essential to make sure the bladder empties
      regularly in the postoperative period, especially in day-case surgery or in
      patients receiving opioid analgesia or after epidural anaesthesia.

PMID- 8572391
TI  - [Management of intraoperative erection by penile block].
AB  - Erection during endoscopic or penile surgery is a troublesome event. In this case
      report, the erection was first treated with intracavernous injection of
      etilefrine (8 mg) and detumescence was obtained rapidly. However, one hour later,
      the erection occurred again. Therefore a dorsal penile nerve block was performed
      by the median route, using 8 mL of 0.25% bupivacaine injected into the subpubic
      space. Mechanisms and treatments of intraoperative erections are discussed.
      Repeated intracavernous injections of vasoactive drugs may be dangerous, whereas
      a penile nerve block carries a lower risk of cardiovascular complications and
      provides an improved postoperative analgesia.

PMID- 8572392
TI  - [Saccharomyces boulardii fungemia in a patient with severe burns].
AB  - A case of Saccharomyces boulardii fungaemia in a burn patient is reported. S.
      boulardii was administered in order to improve the digestive tolerance to enteral
      nutrition. After a surgical procedure, a sepsis syndrome occurred, with a white
      blood cell count increase, abdominal meteorism and respiratory insufficiency,
      associated with seven blood cultures positive to S. boulardii. Digestive
      translocation of the yeast seems to be the most likely origin of this fungaemia.
      Some fungaemias from S. boulardii have been published. However it is not usual to
      find such severe clinical features as in our case which leads us to reconsider
      the therapeutic use of S. boulardii in situations including a gastrointestinal
      tract suffering.

PMID- 8572393
TI  - [Clostridium perfringens septicemia associated with foodborne toxic infection and
      abortion].
AB  - A 32-year-old pregnant woman with poor life and hygiene conditions presented with
      premature labour, fever and diarrhoea. After admission she gave birth to a
      stillborn child. The examination revealed a septicaemia with massive haemolysis
      and renal failure. Six blood cultures obtained on admission yielded Clostridium
      perfringens. The outcome was favourable after an adapted antibiomicrobial
      therapy. This case illustrates the potential severity of Clostridium perfringens
      foodborne toxi-infection which can lead to abortion and septicaemia with massive
      haemolysis.

PMID- 8572394
TI  - [Severe forms of pseudomembranous colitis caused by Clostridium difficile].
AB  - Clostridium difficile causes a broad spectrum of enteric diseases in humans,
      ranging from mild antibiotic-associated diarrhoea to more severe pseudomembranous
      colitis. The authors report four cases of life-threatening pseudomembranous
      colitis with haemodynamic changes. Infection due to Clostridium difficile should
      be kept in mind whenever a patient undergoing antibiotic therapy develops a
      symptomatology of an acute abdomen.

PMID- 8572395
TI  - [Massive entero-mesenteric infarction. A possible role of ostial stenosis of
      digestive arteries].
AB  - A case is reported of a 35-year-old woman who sustained a massive intestinal
      infarction requiring a total resection of small intestine and the colon, with a
      terminal duodenostomy. Preoperative arteriography and intraoperative findings at
      laparotomy showed a thrombosis of coeliac trunc, superior and inferior mesenteric
      arteries, originating possibly from a non atheromatous ostial stenosis of these
      vessels. The blood supply to stomach, duodenum, liver and spleen was maintained
      through collaterals from diaphragm. Postoperatively a dehiscence of duodenostomy
      suture occurred with a spontaneous favourable outcome. The closure of external
      duodenostomy orifice required an endoscopic aspirational gastrostomy. The patient
      was discharged with the perspective of intestinal transplantation, her nutrition
      being provided through an ambulatory parenteral nutritional support unit. A
      symptomatology of chronic mesenteric ischaemia should lead to an angiography of
      digestive arteries not only with a diagnostic but also a possible therapeutic
      goal using angioplasty techniques.

PMID- 8572396
TI  - [Transient arrhythmia disclosing major glycine poisoning during hysteroscopy].
AB  - We report the case of a 41-year-old ASA I patient who experienced during
      endometrial resection a transient idioventricular cardiac rhythm with hypotension
      related to a major glycine intoxication. The total volume of absorbed irrigating
      fluid was over six liters when these clinical signs occurred. The biological data
      were as following: Na = 89 mmol.L-1, Cl = 60 mmol.L-1 and osmolarity = 215 mOsm.L
      1. Simultaneously, the glycine concentration in the plasma was 54.6 mmol.L-1, i.e
      160 times higher than the normal value. The clinical course was unremarkable
      except vomiting. The treatment included only the administration of a diuretic
      agent, as the correction of the disorder took place spontaneously. The paucity of
      clinical symptoms when compared to the severity of the biological disorders
      explain why preventive measures are essential in this type of surgery.

PMID- 8572397
TI  - [Patient evaluation of the quality of anesthesia management].
AB  - A questionnaire completed by 90 adults after ENT or stomatological surgery showed
      that most of them were anxious preoperatively, mainly because of anaesthesia and
      that a "personalized" preanaesthetic examination was the most efficient means to
      decrease it. Although a majority of them was satisfied with the anaesthetic care,
      anaesthetic morbidity remains important. The personalization of pre, per and
      postanaesthetic management by the same anaesthetist is probably the best means
      for improving the quality of care.

PMID- 8572398
TI  - [Curarization in surgery for strabismus in children: what is it worth?].

PMID- 8572399
TI  - [Is it useful to collect blood drained during the 6 postoperative hours in
      orthopedic surgery?].

PMID- 8572400
TI  - [Transfusion technique in neurosurgery: normovolemic hemodilution or
      autotransfusion?].

PMID- 8572401
TI  - [Which technique for retrograde catheterization of the jugular vein?].

PMID- 8572402
TI  - [Right extrapericardial post-traumatic hernia of the heart: a peculiar
      symptomatology].

PMID- 8572403
TI  - [Ambulatory surgery: where are we? Elements for answering. . ].

PMID- 8572404
TI  - [Effects of mechanical ventilation with PEEP on right to left intra-cardiac shunt
      caused by patent foramen ovale].
AB  - OBJECTIVE: To assess the presence of a patent foramen ovale (PFO) using colloid
      contrast transoesophageal echocardiography in mechanically ventilated patient
      with and without PEEP and it repercussion on PaO2. STUDY DESIGN: Prospective open
      before-after trial. PATIENTS: Forty-nine mechanically ventilated patients with
      respiratory failure (PaO2/FiO2 < 250). METHODS: PEEP assessment before and after
      adding a PEEP = 10 cmH2O. At each level of PEEP, semi-quantification of PFO was
      performed and arterial blood gases were withdrawn at FiO2 = 1, with 15 min at
      each level. Semi-quantification of the right-to-left intra cardiac shunt through
      a patent foramen ovale was obtained using the quantity of microbubbles in the
      left atrium on a basal short axis view. RESULTS: A PFO was detected in 11 out of
      49 patients (22%). A right-to-left shunt developed in one and worsen in three
      patients when PEEP was added. In patients without a PFO, PaO2 increased
      significantly (from 119 +/- 10 mmHg to 145 +/- 10 mmHg, P < 0.001). In patients
      with a PFO, non significant changes occurred (118 +/- 15 mmHg to 120 +/- 17
      mmHg). After adding PEEP, the difference between the two groups was significant
      (ANOVA, P < 0.05). Moreover, a PFO was present during the whole respiratory cycle
      in two out of 11 patients. These 2 patients exhibited a PaO2 < 100 mmHg with or
      without PEEP. CONCLUSION: This study suggests that mechanical ventilation with
      PEEP enhances an intracardiac right-to-left shunt through a PFO. This condition
      is responsible for the lack of improvement in blood oxygenation when PEEP is
      added. When a PFO is present all over the respiratory cycle, or when the
      oxygenation is worsened with PEEP, this positive pressure ventilation should be
      avoided. The deleterious consequences of mechanical ventilation on venous return
      may be minimized by partial ventilation and weaning from ventilator.

PMID- 8572405
TI  - [Comparison of the effects of ketorolac and aspirin on hemostasis in the rabbit].
AB  - OBJECTIVE: Comparison of ketorolac with aspirin and placebo for the
      antithrombotic activity using the Folts' model of experimental arterial
      thrombosis and the perioperative blood loss. STUDY DESIGN: Experimental
      randomized blinded study anaesthetized, tracheotomized and mechanically
      ventilated. Carotid blood flow variations were detected by a probe directly
      inserted around the artery and monitored by an electromagnetic flowmeter. A
      segment of the exposed carotid artery was de-endothelialized by gently squeezing
      the artery with a needle holder forceps, and an external constrictor was placed
      around it (stenosis 60%), to induce cyclic flow reductions (CFR). During 20 min,
      CFR rate was assessed. Animals were then randomized in 3 groups of 9: ketorolac
      (K) 1 mg.kg-1, aspirin (A) 10 mg.kg-1 or saline (S), injected intravenously
      (peripheral ear vein). After drug administration, CFR rate was assessed over 20
      min, to determine the potential antithrombotic activity of the drug (curative
      phase). Thereafter, the opposite carotid artery was injured and stenosed and the
      occurrence of CFR was assessed over 20 min (preventive phase). The amount of
      blood loss of a xipho-pubic laparotomy with a spleen section was also measured 30
      min after drug administration. RESULTS: In all untreated animals, CFRs developed
      with a mean rate of 4 cycles/20 min. Aspirin completely abolished CFR during the
      curative phase in all rabbits, except in one. No effect was observed during this
      phase with ketorolac or saline. During the preventive phase, a partial inhibition
      of CFRs was induced by ketorolac and aspirin. Peri-operative bleeding was not
      increased significantly by ketorolac or aspirin. Postinjection bleeding-time did
      not differ between the three groups. CONCLUSIONS: Ketorolac (1mg.kg-1) has not a
      strong antithrombotic activity. Ketorolac and aspirin do not increase peri
      operative blood loss, and therefore do not seem to strongly interfere with
      haemostasis in the rabbit.

PMID- 8572406
TI  - [Anesthesia for hand surgery in patients with epidermolysis bullosa].
AB  - OBJECTIVE: To report on the anaesthetic management with axillary block of
      patients suffering from recessive dystrophic epidermolysis bullosa (RDEB),
      undergoing repetitive surgery of the hand. STUDY DESIGN: Retrospective analysis
      of a case series. PATIENTS: Twenty-two patients, including 11 children less than
      8-year-old and with a body weight under 20 kg, treated since 1988, were
      considered. METHODS: For surgery, including usually three stages at a 7-day
      interval, an axillary block was placed when feasible, after oral premedication
      midazolam (0.1-0.2 mg.kg-1) with a 25 gauge needle in patients of less than 30 kg
      of body weight and 22 gauge beyond. The local anaesthetic mixture included 2%
      lidocaine (5-10 mg.kg-1) and 0.5% bupivacaine (2-3 mg.kg-1). A catheter for
      repetitive injections had not been inserted. For children less than 10-year-old a
      parent was present in the theater during all the course of operation. RESULTS:
      Between 1988 and 1995, 22 patients underwent 160 operative interventions on 54
      hands. Regional anaesthesia was used in 142 cases, including 140 axillary and 2
      interscalene blocks. General anaesthesia was only required in 20 cases, either
      alone or associated with regional anaesthesia. The success rate of axillary
      blocks was 98%. DISCUSSION: For surgery of the hand in patients with RDEB, we
      switched in 1988 from general anaesthesia with ketamine to axillary block, even
      in young children, as it is closer to the no-touch principle, which is essential
      to prevent from blistering. In comparison to general anaesthesia, regional
      anaesthesia raises neither the problems of airway and vascular access, nor those
      of instrumental monitoring. The main factors of success with regional anaesthesia
      are technical skills, expertise in the management of patients with RDEB and
      parental presence in the operating room which makes the procedure less stressful
      for children.

PMID- 8572407
TI  - [Indications for the use of magnesium in anesthesia and intensive care].
AB  - Magnesium (Mg), a cofactor in numerous enzymatic reactions, is often ignored by
      clinicians, as the symptomatology of Mg depletion is not specific and usually
      associated with that of the cause of the depletion. Furthermore, the plasma Mg
      concentration (0.8 to 1.1 mmol.L-1) is only equivalent to one percent of the
      total body content. A Mg deficit may exist while plasma Mg concentration is
      normal. Therefore other techniques for Mg assessment, such as the repletion test,
      as well as red blood cell and lymphocyte concentrations have been used. A renewed
      interest for Mg occurred as numerous studies have shown the therapeutic
      efficiency of Mg and as the mechanisms of its haemodynamic effects have been
      recognized. Mg regulates Na-K-ATPase activity, K channels activity and, most of
      all, it is a natural calcium channel blocking agent. These properties explain its
      important place in electrophysiology of myocardial cells and the effects on the
      tension of smooth muscles, resulting in a vasodilation and a bronchodilation
      respectively. The antagonistic effect of Mg on calcium decreases the presynaptic
      release of acetylcholine at the neuromuscular junction and the release of
      epinephrine at the peripheral sympathetic nerves and the adrenals. Mg potentiates
      the effect of non-depolarizing muscle relaxants. A Mg deficiency occurs often in
      ICU patients, in alcoholics and during use of diuretics. Simultaneous
      administration of Mg is often required for treatment of potassium deficiency. Mg
      has an anti-arrhythmic effect towards digoxin-mediated dysrhythmias and torsades
      de pointes, and can be efficient in other arrhythmias. Systematic use of Mg seems
      to decrease mortality of acute myocardial infarction and is justified during
      cardiac surgery, often associated with hypomagnesemia, because of vasodilation of
      coronary arteries and in order to prevent occurrence of arrhythmias. Mg, because
      of its calcium channel blocking properties and as it lowers the release of
      epinephrine, is indicated for surgery of pheochromocytoma. In eclamptic and pre
      eclamptic patients, the use of Mg is valuable, but not as an anti-epileptic
      agent. Other clinical uses of Mg have been proposed, but they are either
      anecdotal or of uncertain efficiency.

PMID- 8572408
TI  - [Diagnosis of heart arrest caused by CO2 embolism during laparoscopic surgery by
      monitoring of aortic blood flow and capnography].
AB  - We report the case of a 25-year-old woman undergoing a laparoscopic
      cholecystectomy, who suffered, one min after the beginning of intraperitoneal
      insufflation of CO2 (2.5 L at a pressure of 10 mmHg), a sudden decrease to 0.8
      L.min-1 of the aortic blood flow (ABF), monitored in the descending aorta by an
      oesophageal echo-Doppler probe, associated with a decrease of PetCO2 to 15 mmHg
      and of SpO2 readings to 88%. Despite the lack of simultaneous changes in heart
      rate and arterial pressure, pulmonary gas embolism (GE) was suspected. The
      pneumoperitoneum was exsufflated and CPR was started because of circulatory
      inefficiency. Ten min later, efficient spontaneous cardiac activity restarted,
      whereas PetCO2 and ABF returned rapidly to normal values. At this time, a typical
      gas noise was clearly obtained through the oesophageal Doppler transducer. The
      patient remained in deep coma (GCS:6) with a left sided hemiplegia. However, she
      fully recovered after four sessions of hyperbaric oxygenation. Simultaneous
      continuous monitoring of ABF and PetCO2 allows an undelayed recognition of major
      circulatory disturbances, before significant changes in heart rate and arterial
      pressure occur.

PMID- 8572409
TI  - [Cesarean section and left ventricular failure caused by coronary artery disease:
      anesthetic management].
AB  - A Caesarean section was performed in a 34-year-old patient experiencing a major
      left heart failure secondary to an anterior myocardial infarction which occurred
      four years before. At the end of pregnancy, she developed a mild pulmonary
      hypertension. Caesarean section was decided to maintain a stable haemodynamic
      status. For the same reason, general anaesthesia with etomidate was preferred
      rather than epidural analgesia. Haemodynamic monitoring allowed the adequate
      management of blood pressure, heart rate, pulmonary blood pressure and arterial
      oxygen saturation. Postoperative analgesia was obtained with opioids administered
      epidurally.

PMID- 8572411
TI  - [Traumatic diaphragmatic rupture with delayed unusual disclosure].
AB  - The authors report the case of a delayed presentation of a traumatic
      diaphragmatic rupture in a 22-year-old patient admitted to hospital for a minor
      surgical procedure under general anaesthesia. Nine months before, he had a road
      traffic accident with a minor thoracic trauma. Three days after surgery, the
      patient was readmitted for a tension hydrothorax due to the herniation and the
      perforation of the stomach into the left pleural cavity. Such a delayed
      presentation of a traumatic diaphragmatic rupture remains uncommon. The
      peroperative ventilatory factors involved in the development of the hernia are
      discussed.

PMID- 8572410
TI  - [Tetraparesis in an infant after prolonged administration of pancuronium].
AB  - Long-term administration of pancuronium for ventilatory support of adults with
      ARDS may result in severe tetraparesis, with areflexia and atrophy of distal
      muscles. This adverse effect occurs rarely in paediatric intensive care units. We
      describe a case of tetraparesis after prolonged pancuronium infusion in a 9-month
      old girl who experienced a severe bronchopneumonia caused by para-influenza
      virus, requiring endotracheal intubation and mechanical ventilation. To decrease
      chest wall rigidity, pancuronium was administered over 11 days, with a total dose
      of approximately 120 mg of pancuronium bromide. The day after discontinuation of
      the muscle relaxant she had a severe tetraplegia with areflexia, but normal head
      movements. Electromyography showed a normal neuromuscular transmission. She
      recovered from tetraplegia three months later. Other causes of peripheral
      neuropathy were eliminated. Electroencephalograms and head CT-scans were normal.
      The recovery pattern observed in our patient corresponded to the process of
      regeneration seen after axonal degeneration. It is suggested that these
      neuromuscular complications were caused by prolonged high-dosage pancuronium
      treatment, associated with corticosteroid and aminoglycoside administration.

PMID- 8572412
TI  - [Severe acute buflomedil poisoning].
AB  - The severity of the acute intoxication from buflomedil, a vasodilator with
      papaverinic and alpha-adrenolytic effects, remains generally underestimated. We
      report the case of a 18-year-old girl who ingested a high amount of buflomedil.
      Two hours later, she developed seizures and ventricular arrhythmias. On admission
      to the ICU, she was in circulatory arrest followed by deep coma with mydriasis
      (GCS = 3). Buflomedil blood concentration, 2 hours after admission, was 97.3 mg.L
      1. Toxicological screening for other drugs was negative. Therapy included
      external chest compressions tracheal intubation, mechanical ventilation,
      epinephrine and gastric lavage. The haemodynamic status improved within the first
      24 h, although she remained comatose until the fifth day. She was discharged the
      eight day after her admission. This observation demonstrates that the potential
      severity of buflomedil poisoning is mainly due to early cardiac complications.
      Treatment remains purely supportive.

PMID- 8572413
TI  - [Blood-patch treatment of headache occurring after post-dural puncture at the
      thoracic level].
AB  - A 23-year-old woman experienced headache following a high thoracic epidural
      analgesia to control postoperative pain after thoracoscopic treatment of a
      recurrent pneumothorax. On fourth postoperative day, a blood patch has been sited
      with 17 mL of autologous blood, injected into the thoracic epidural space at T1
      T2 level, which was immediately effective. Except a mild and transient cervical
      pain during the procedure, no other complication occurred. The technique of
      thoracic blood patch is similar to the lumbar one, except some minor
      modifications. According to this case of a thoracic epidural blood patch which is
      seemingly the first one reported in the literature and our expertise with two
      other unpublished cases, a volume of 10 mL of blood may be sufficient and free of
      adverse effects.

PMID- 8572414
TI  - [Interscalenic block: accidental catheterization of the epidural space].
AB  - A case is reported of inadvertent insertion of a brachial plexus catheter into
      the cervical epidural space, at the sitting of an interscalene block for
      postoperative analgesia, during the recovery from general anaesthesia after
      surgical repair of a rupture of the rotator cuff of the shoulder. No features of
      cervical epidural anaesthesia were seen after the first injection of local
      anaesthetic, as it was made through the catheter insertion cannula. Once
      inserted, the catheter position was checked prior to the second injection of
      local anaesthetic. The X-ray obtained after catheter opacification showed the
      penetration of contrast medium into the epidural space. In our case, two out of
      the three means of prevention of this complication were not possible: a) sitting
      of the interscalene block before induction of anaesthesia, as the insertion
      conditions of the catheter are better in a conscious, sitting patient; b)
      adequate cannula orientation (namely medial, dorsal and slightly caudal); c)
      routine X-ray control of the catheter position before the first injection,
      associated with careful clinical monitoring for 30 min after each local
      anaesthetic injection.

PMID- 8572415
TI  - [Perioperative transfusion practices at the Limoge University Hospital].

PMID- 8572416
TI  - [French Society of Anesthesia and Intensive Care. Arterial catheterization and
      invasive measurement of blood pressure in anesthesia and intensive care in
      adults].
AB  - A group of 13 experts appointed by the French Society of Anaesthesia and
      Intensive Care has produced the following guidelines for arterial catheterisation
      and invasive measurement of systemic arterial blood pressure in adults. Teflon or
      polyurethane catheters are recommended with a maximal size of 18 gauge for
      femoral and axillary arteries and 20 gauge for the others. For small arteries
      (radial and pedious arteries) a maximal length of 3-5 cm should be preferred. The
      benefit of heparin-coating is not documented. Incorporation of salts for
      radiopacity is useless and increases thrombogenicity. Use of a flush device with
      a constant flow of 2 mL.h-1 and a fast flush valve connected to normal saline
      under pressure is recommended. Manual intermittent flushing with a syringe is
      contra-indicated. Addition of heparin (2500 IU.500 mL-1 of flush solution)
      increases the duration of catheter patency and is recommended for
      catheterisations of more than 24 h duration. Ready for use devices are to be
      preferred. Distortion of pressure wave may be minimized by employing low volume,
      low compliance, low resistance devices. The number of connections should be as
      low as possible and all of Luer-lock type. The stopcocks should be clearly
      identified to minimize the risk of accidental intra-arterial injection. The
      device should be transparent for disclosure of bubbles, which lead to waveform
      distortion. For catheter placement the operator should follow the usual
      preparation as for any aseptic surgical procedure with cap, mask, gloves and
      sterile towel. The insertion site is prepped either with chlorhexidine or
      povidone-iodine. In the conscious patient, local anaesthesia by injection and/or
      topical application (EMLA) is recommended. Direct arterial puncture should be
      preferred rather than transfixion. Catheterisation of deep vessels is facilitated
      by Seldinger technique, which is recommended whatever the site of placement when
      long term monitoring and/or difficulties of insertion are foreseen. The radial
      artery is the site of choice for elective cases. The non-dominant hand should be
      preferred. Puncture must be preceded by assessment of adequacy of the collateral
      flow by the Alien test. The femoral artery is a valuable site for emergency
      situations. Before catheterisation, the artery should be auscultated for a
      murmur. Puncture of a vascular prosthesis is contra-indicated. The dressing
      should be changed every four days only. Sites of blood withdrawal should be
      manipulated with compresses soaked with chlorhexidine or povidone-iodine. The
      arterial catheter is only changed in case of evidence of local infection or
      ischaemia. The catheter removal should be considered as an aseptic surgical
      procedure. The catheter completeness has to be checked. A systematic culture of
      the catheter is not required.

PMID- 8572417
TI  - [Invasive aspergillosis during resuscitation].

PMID- 8572418
TI  - [Is peroperative transfusion of autologous blood beneficial to a patient with
      homozygotic sickle cell disease?].

PMID- 8572419
TI  - [Isolated hyperchloremia in preoperative evaluation].

PMID- 8572420
TI  - [EMLA cream: prudent use and warnings].

PMID- 8572421
TI  - Evaluation of nonlinear dynamics in postural steadiness time series.
AB  - Fractal and correlation dimensions have been computed for time series obtained
      from tests of balance (postural steadiness). Although these measures appear to be
      reliable and differentiate subject groups, it has become clear that random
      (noise) time series may have finite dimensions and appear to demonstrate dynamics
      characteristic of nonlinear systems. Consequently, it is necessary to apply a
      test to distinguish a time series with putative nonlinear dynamics from random
      noise. A simple predictor was utilized to compare center of pressure (COP) time
      series with surrogate data constructed to have similar time and frequency domain
      characteristics. It was found that the original time series was more predictable
      than the surrogate data, suggesting that the COP data is derived from a nonlinear
      system.

PMID- 8572422
TI  - The effect of elevated intracranial pressure on the vibrational response of the
      ovine head.
AB  - Although potentially fatal increases in intracranial pressure (ICP) can occur in
      a number of pathological conditions, there is no reliable and noninvasive
      procedure to detect ICP elevation and quantitatively monitor changes over time.
      In this experimental study, the relationships between ICP elevation and the
      vibrational response of the head were determined. An ovine animal model was
      employed in which incremental increases in ICP were elicited and directly
      measured through intraventricular cannulae. At each ICP increment, a vibration
      source elicited a flexural response of the animal's head that was measured at
      four locations on the skull using accelerometers. Spectral analysis of the
      responses showed changes in proportion to ICP change up to roughly 20 cm H2O (15
      mm Hg) above normal; a clinically significant range. Both magnitude and phase
      changes at frequencies between 4 and 7 kHz correlated well (gamma > 0.92) with
      ICP across the study group. These findings suggest that the vibrational response
      of the head can be used to monitor changes in ICP noninvasively.

PMID- 8572423
TI  - On the influence of volume currents and extended sources on neuromagnetic fields:
      a simulation study.
AB  - The influence of volume currents on the magnetic field is an important question
      in magnetoencephalography since the spherical volume conductor is still widely
      used for source localization. In theory, the magnetic field of a radial dipole in
      a homogeneous sphere is zero. In realistic models of the head, the field is
      suppressed when compared with a tangential dipole. To determine the influence of
      the volume currents, this suppression ratio (magnetic field of the radial dipole
      divided by the field of the tangential dipole) needs to be quantified. Large
      scale finite element method models of the human head and the rabbit head were
      constructed and the suppression ratio was computed. The computed suppression
      value of 0.28 in the rabbit head was similar to the previously measured
      experimental value. In the human head, an average suppression ratio of 0.19 +/-
      0.07 was found for different regions and depths in the gray matter. It was found
      that the computed magnetic field of radial sources varied significantly with the
      conductivities of the surrounding tissues where the dipole was located. We also
      modeled the magnetic field of an epileptic interictal spike in a finite element
      model of the rabbit head with a single dipole and with extended sources of
      varying length (1-8 mm). The extended source models developed were based on
      invasive measurements of an interictal spike within the rabbit brain. The field
      patterns of the small (1-2 mm) extended sources were similar to a single dipolar
      source and begin to deviate significantly from a dipolar field for the larger
      extended sources (6-8 mm).

PMID- 8572424
TI  - Serial distribution of airway diameters from input impedance and computed
      tomography.
AB  - Indirect measures of airway diameter such as respiratory system input impedance
      (Zin) have been widely used to infer or quantify bronchoconstriction, or
      bronchodilation. One such measure, Zin above 100 Hz has been shown to be
      primarily influenced by airway geometry and airway walls but not by lung and
      chest wall tissues. We used a recently developed method based on a complex
      asymmetrically branched network of tubes with nonrigid walls to analyze Zin from
      100 to 2,000 Hz in control and bronchoconstricted (histamine injection) dogs. The
      resulting estimates of airway diameters indicated that peripheral airways were
      constricted far more (approximately 30% of their control diameters) than central
      airways (i.e., 0% in the trachea). Separate measurements of changes in airway
      diameters were made in an excised dog lung using high resolution computed
      tomography. The observed changes in airway diameter between lung volumes of total
      lung capacity (TLC) and functional residual capacity (FRC) were quantitatively
      consistent with those obtained from Zin data in our control dogs at FRC. We
      conclude that this systems identification method can be used to estimate the
      distribution of airway diameters from Zin.

PMID- 8572425
TI  - Fluid dynamics of venous valve closure.
AB  - In vitro experiment was performed on a stented bovine jugular vein valve (VV, 14
      mm I.D. x 2 cm long) and a stentless bovine jugular vein valve conduit (10 mm
      I.D. x 6 cm long) in a hydraulic flow loop with a downstream oscillatory pressure
      source to mimic respiratory changes. Simultaneous measurements were made on the
      valve opening area, conduit and sinus diameter changes using a specially designed
      laser optic system. Visualization of flow fields both proximal and distal to the
      venous valve, and the valve opening area were simultaneously recorded by using
      two video cameras. Laser Doppler anemometer surveys were made at three cross
      sections: the valve inlet, the valve exist, and 2 cm downstream of the venous
      valve to quantity flow reflux at valve closure. The experiment confirmed that the
      VV is a pressure-operated rather than a flow-driven device and that little or no
      reflux is needed to close the valve completely. The experiment further
      demonstrated that the VV sinus expands rapidly against back pressure, a critical
      character to consider in venous prosthesis design.

PMID- 8572426
TI  - Nonlinear closed-loop control system for intracranial pressure regulation.
AB  - A nonlinear closed-loop control system with flat pressure-versus-flow
      characteristics that is aimed at regulating intracranial pressure (ICP) by
      adjusting the volume of cerebral spinal fluid (CSF) was designed, built, and
      tested. The control system design allows both the pressure setpoint and
      hysteresis to be adjusted to overcome the difficulties inherent in differential
      pressure-activated, fixed resistance, open-loop shunts. A dynamic six-compartment
      bench-top fluid system, which mimics the cerebral spinal fluid system, was
      designed, built, and tested. A computer simulation was developed which included
      the nonlinear on-off controller with hysteresis and a sixth-order, linear,
      multicompartmental model of the CSF system. The computer model and in vitro
      system results showed the ability of the system to track and compensate for
      pressure variations above and below normal as well as for spurious outputs that
      mimic such in vivo problems as blood pressure changes, sneezing, or coughing.
      There was one discrepancy between the simulated and in vitro results. The in
      vitro system had a higher rate of increase in pressure due to the more rigid
      compliance of the materials used, whereas the computer model compliance, based on
      the basal in vivo compliance of the CSF system, was less rigid. Based on these
      findings, the controller was modified to account for short-duration, extremely
      elevated pressures.

PMID- 8572427
TI  - Texture analysis of protein distribution images to find differences due to aging
      and superfusion.
AB  - Many pathologies are age-related, e.g., cardiovascular disease generally occurs
      in midlife and cancer later in life. This suggests that aging predisposes the
      body to pathology. Plasma protein spatial distribution images of rat mesentery
      extracellular matrix (ECM) show texture due to the ECM structures, and there is
      an age-related decrease in tissue protein that may be related to matrix structure
      changes. The objective of this study was to compare changes in protein image
      texture under two conditions: superfusion with normal saline solution and aging.
      The decrease in soluble protein concentration during superfusion is a washout
      process, while the mechanism for the age-related decrease in tissue protein is
      unknown. Therefore, effects of aging and superfusion on tissue protein image
      texture were compared. Spatial co-occurrence matrix and Fourier analysis
      techniques have been used for texture evaluation. Superfused images showed a more
      uniform protein texture. There were gradual age-related changes in image texture
      parameters. Entropy increased with age from 140 to 630 days, indicating that
      protein distribution became more disorganized. The results suggest that changes
      in protein image texture are due to age-related alterations in matrix structure
      because removing only protein by superfusion had opposite effects on texture
      parameters.

PMID- 8572428
TI  - Direct demonstration of radiolabeled von Willebrand factor binding to platelet
      glycoprotein Ib and IIb-IIIa in the presence of shear stress.
AB  - In this study it is demonstrated for the first time that shear stress induces the
      binding of exogenous von Willebrand factor (vWF) multimers to platelets. The vWF
      preparations used were: 125I-vWF purified from human cryoprecipitate (and
      including all vWF multimers present in normal plasma); and 35S-cysteine-vWF
      secreted by human umbilical vein endothelial cells (HUVECs) (and containing
      unusually large vWF forms, as well as all plasma-type vWF multimers). Direct
      shear-induced binding to washed platelets (300-360 x 10(3)/microliters) of
      radiolabeled vWF was maximum at 60-120 dynes/cm2 evaluated at 30 sec and was in
      extent about one-quarter of the binding stimulated by ristocetin after 3 min of
      incubation. The shear-induced binding of only a small percentage of added
      radiolabeled vWF was sufficient to initiate aggregation. Radiolabeled vWF
      attached to both glycoprotein (GP) Ib and GPIIb-IIIa receptors in the shear
      field, with complete inhibition of binding occurring with simultaneous blockade
      of both receptors. Binding was potentiated by ADP released from sheared
      platelets.

PMID- 8572429
TI  - Pressure peaking in pulsatile flow through arterial tree structures.
AB  - An analytical iterative scheme is presented for computing the local
      characteristics of pressure and flow waves as they progress along a tree
      structure and become modified by wave reflections. Results are obtained to
      illustrate the phenomenon of pressure peaking under two different sets of
      circumstances. In the first case, the propagation of a single harmonic wave along
      a simple tree is considered, where wave reflections modify the amplitude of the
      pressure wave as it travels. In the second case, the propagation of a composite
      wave along a tree with multiple branches is considered, where wave reflections
      modify the shape of the wave as it travels and cause it to peak. The results
      demonstrate unambiguously that the root cause of this phenomenon is wave
      reflections caused by stepwise decreases in admittance, as has been previously
      suggested, rather than due to nonlinear interactions, as has also been previously
      suggested. It is shown clearly that even when wave reflections combine linearly,
      they lead to considerable peaking in the pressure waveform.

PMID- 8572430
TI  - Arterial wave propagation phenomena, ventricular work, and power dissipation.
AB  - The effects of wave propagation phenomena, namely global reflection coefficient
      (gamma G[omega]) and pulse wave velocity (Cph), are studied in a model of the
      coupled left ventricle/arterial system. The left ventricle consists of a time
      varying elastance, while the arterial system is modeled as a single, uniform,
      elastic tube terminating in a complex load. Manipulation of model parameters
      allowed for the precise control of gamma G(omega) and Cph independent of each
      other, peripheral resistance, and characteristic impedance. Reduction of gamma
      G(omega) and Cph were achieved through increases in load compliance and tube
      compliance, respectively. The equations describing the system were solved for
      left ventricular and aortic pressures and aortic flow. From these, stroke volume
      (SV), left ventricular stroke work (SW), and steady (Ws), oscillatory (Wo), and
      total power dissipation (Wt) in the arterial system were calculated. An index of
      arterial system efficiency was the ratio Wo/Wt (%Wo), with lower values
      indicating higher efficiency. Reduction of gamma G(omega) yielded initial
      increases in Ws, while Wo increased for the entire range of gamma G(omega),
      resulting in increased %Wo. This reduced efficiency is imposed on the ventricle,
      resulting in increased SW without increased SV. On the other hand, decreased Cph
      yielded in a steady increase in Ws and a biphasic response in Wo, resulting in
      reduced %Wo for most of the range of reduced Cph. These results suggest that
      differential effects on arterial system efficiency can result from reductions of
      gamma G(omega) and Cph. In terms of compliance, changes in arterial compliance
      can have different effects on efficiency, depending on where the compliance
      change takes place. Reasons for these results are suggested, and the role of
      distributed compliances is raised as a new problem.

PMID- 8572431
TI  - Electrical stimulation of cardiac myocytes.
AB  - The influence of nonuniform cell shape and field orientation on the field
      stimulation thresholds of cardiac myocytes was studied both experimentally and
      computationally. The percent change in excitation threshold, which was studied
      with patch clamp technique, was found to be 182 +/- 83.1% (mean +/- SD) higher
      when the electric field (EF) was parallel to the transverse cell axis versus the
      longitudinal axis (p < 0.0006). On reversing the polarity of the applied EF, the
      percentage change in threshold was observed to increase by 98.9 +/- 71.0% (p <
      0.0002), implying asymmetry of the stimulation threshold of isolated myocytes.
      Finite element models were made to investigate the distribution of the
      transmembrane potential of these experimentally studied myocytes. A typical cell
      model showed that the maximum transmembrane potential induced on opposite ends of
      the cell was 39.1 mV and -46.5 mV for longitudinal field (aligned with the long
      axis of the cell), but was 40.5 mV and -44.8 mV for transverse field (aligned
      with the short axis of the cell). More significantly, it was found that the
      maximum transmembrane potential occurred at discrete points or "hot spots" on the
      cell membrane. It is hypothesized that the depolarization of the cell initiates
      at the hot spot and then spreads over the entire cell. The different excitation
      thresholds for different polarities of the applied EF can be explained by the
      different maximum induced at the opposite ends of the cell.

PMID- 8572432
TI  - A model of electrical activity and cytosolic calcium dynamics in vascular
      endothelial cells in response to fluid shear stress.
AB  - A mathematical model is proposed to describe the intracellular Ca2+ (Cai)
      transient and electrical activity of vascular endothelial cells (VEC) elicited by
      fluid shear stress (tau). The intracellular Ca2+ store of the model VEC is
      comprised of a Cai-sensitive (sc) and an inositol (1,4,5)-trisphosphate (IP3)
      sensitive compartment (dc). The dc [Ca2+] is refilled by the sc whose [Ca2+] is
      the same as extracellular [Ca2+]. IP3 produced by the tau-deformed
      mechanoreceptors discharges the dc Ca2+ into the cytosol. The increase of
      cytosolic [Ca2+] induces Ca2+ release (CICR) from the sc. The raised Cai
      activates a Cai-activated K+ current (IK,Ca) and inhibits IP3 production. The
      cell membrane potential is determined by IK,Ca, voltage-dependent Na+ and K+
      currents. Steady tau > 0.1 dyne/cm2 elicits a Cai transient which reaches peak
      value at 19-54 sec. The peak Cai varies sigmoidally with Log10(tau) with a
      maximal peak Cai of 150 nM at tau = 4 dynes/cm2. Step increases of tau fail to
      elicit a Ca2+ response in cells previously stimulated by a lower shear. The Ca2+
      response gradually decreases with repetitive tau stimuli. Pulsatile shear elicits
      two to three times higher Cai and hyperpolarizes the cell more than steady shear
      of the same magnitude. The simulated Ca2+ responses to tau are quantitatively and
      qualitatively similar to those observed in cultured VEC. The model provides a
      possible explanation of why the vasodilating stimulus is greater for pulsatile
      flow than for nonpulsatile flow.

PMID- 8572433
TI  - Glucose biosensors based on oxygen electrode with sandwich-type membranes.
AB  - A glucose biosensor based on an amperometric oxygen electrode has been developed.
      Polycarbonate and Silastic membranes were assembled (glued together) to form a
      multilayer sandwich glucose diffusion barrier. The effects of the glue layer
      composition and thickness of the Silastic membrane on sensor response parameters
      have been investigated in order to optimize the sensor. The parameters measured
      were the sensitivity, the concentration range of the linear dependence of the
      sensor response to glucose, and the long-term operation time. The sensors with
      the sandwich-type glucose diffusion membrane (Silastic membrane prepared from 20%
      Silastic suspension, glue layer prepared from polyurethane, 0.5 w/v % in ThF
      solution and standard polycarbonate membrane) demonstrated linearity of response
      up to 520 mg/dl glucose at 25 degrees C and up to 400 mg/dl at 37 degrees C.
      These sensor showed good reproducibility of response without significant
      interference effects (from 1 to 5% of the background current value). The long
      term continuous operational time of the sensors was over 40 days at 37 degrees C,
      and over 60 days at 25 degrees C.

PMID- 8572435
TI  - Confirmation of blind endotracheal tube placement.

PMID- 8572434
TI  - Combined cardiac marker approach with adjunct two-dimensional echocardiography to
      diagnose acute myocardial infarction in the emergency department.
AB  - STUDY OBJECTIVE: To evaluate a combined cardiac marker approach with adjunct two
      dimensional echocardiography in diagnosing acute myocardial infarction (AMI) in
      the emergency department. METHODS: This prospective, cohort study enrolled 190
      patients aged 18 years and older who presented to the ED of a county teaching
      hospital and were admitted with chest pain suggestive of AMI. A standardized
      history and physical examination were performed. Serum sampling for myoglobin and
      creatine kinase-MB (CK-MB) was done at the time of presentation (time 0) and 3
      hours later (time 3 hours). An echocardiographic study was obtained, and a left
      ventricular wall motion score was derived. RESULTS: Using World Health
      Organization criteria, 21 patients (11.2%) with AMI were identified. The serum
      markers were found to be clinically and statistically different between AMI and
      non-AMI groups at both time 0 and time 3 hours. Receiver operator characteristic
      curves were used to determine a "positive" myoglobin level at 88.7 ng/mL or
      higher at either time point, and a "positive" CK-MB level at 11.9 ng/mL or
      higher; these were used as the optimal cutoff values to predict AMI in the ED.
      Serum myoglobin was a more sensitive marker (90.5%) than CK-MB (81.0%). However,
      CK-MB was more specific (99.4%) than myoglobin (88.4%). A combination of both
      tests, which was rated positive if either test was positive, was a superior
      predictor overall, with a 100% capture rate of AMI patients and a 91.2%
      specificity. No significant difference in echocardiographic scores was
      appreciated in the AMI group compared with the non-AMI group (16.9 +/- 1.5 versus
      15.3 +/- .5, respectively; P = .3252). CONCLUSION: Serum myoglobin shows greater
      sensitivity but is less specific than CK-MB in the early detection of AMI. Use of
      a combination of both rapid assays during a 3-hour time period in the ED appears
      to be superior to use of either enzyme assay alone. Two-dimensional
      echocardiography does not appear to be helpful in diagnosing AMI in the ED.

PMID- 8572436
TI  - Confirmation of blind endotracheal tube placement.

PMID- 8572437
TI  - Moonlighting revisited.

PMID- 8572438
TI  - Computed tomography and basilar skull fracture.

PMID- 8572439
TI  - The "real" Ottawa ankle rules.

PMID- 8572440
TI  - Delayed in-hospital defibrillation.

PMID- 8572441
TI  - Stomach rupture during CPR.

PMID- 8572442
TI  - Effect of cardiologist ECG review on emergency department practice.
AB  - STUDY OBJECTIVE: To determine the effect of cardiology review of ECGs on
      emergency department practice. METHODS: We carried out a prospective cohort study
      at an urban teaching ED. Our subjects were adult patients undergoing
      electrocardiography. We prospectively collected 1,000 consecutive ECGs and
      classified them by severity according to the following system: class 1, normal or
      minor abnormalities only; class 2, abnormalities with potential to alter case
      management; and class 3, potentially life-threatening abnormalities. Actual ECG
      readings by ED physicians (who had access to computerized interpretations at the
      time of treatment) were compared with those of staff cardiology quality-assurance
      reviewers; if they were not in agreement, an expert cardiology panel blindly
      chose the superior interpretation. Subsequently, an expert emergency physician
      panel reviewed discordant readings for discharged patients to determine the need
      for further action. RESULTS: Of 1,000 ECGs, the readings for 190 (19%) were
      significantly discordant. The expert cardiology panel preferred the ED reading in
      72 cases (38%) and the staff cardiology reading in 118 (62%). In 30 other cases
      no ED reading was recorded in the medical record. Of the 148 cases in which the
      expert cardiology panel agreed with the cardiology reading or there was no ED
      reading, 102 patients were admitted and 46 discharged. Of the 46 discharges, 8
      cardiology readings were categorized as class 1, leaving only 38 cases in which
      the staff cardiology reading might have affected the ED decision to discharge a
      patient. All of these readings were in class 2, with the exception of one
      unclassifiable diagnosis. There were no class 3 readings. On expert emergency
      physician panel review of these 38 ECGs and interpretations, only 8 (.8%, 95%
      confidence interval, .3% to 1.6%) were considered sufficiently important to
      warrant chart review. In actual practice, none of these cases was affected by the
      ECG quality-assurance (QA) process. Two of these patients died during our 1-year
      follow-up. In one of these cases, the ECG QA process could have altered the
      patient's outcome. CONCLUSION: The existing ECG review process as mandated by the
      Joint Commission on Accreditation of Healthcare Organizations (JCAHO) will likely
      have minimal influence on patient outcomes at our institution. We should
      establish the effectiveness of this mandated QA process before committing scarce
      resources to its performance.

PMID- 8572443
TI  - Improved specificity of myoglobin plus carbonic anhydrase assay versus that of
      creatine kinase-MB for early diagnosis of acute myocardial infarction.
AB  - STUDY OBJECTIVE: Carbonic anhydrase III (CA-III) is an enzyme released from
      skeletal muscle in a fixed ratio with myoglobin during cell injury, but unlike
      myoglobin it is not found in cardiac muscle. This study compared the clinical
      utility of serum myoglobin (S-Mgb) in conjunction with the ratio of S-Mgb to CA
      III (S-Mgb/CA-III) versus creatine kinase-MB (CK-MB) for the early diagnosis of
      acute myocardial infarction (AMI). METHODS: This prospective observational study
      set at a university teaching hospital emergency department enrolled 251
      consecutive consenting patients who presented with symptoms consistent with
      cardiac ischemia or infarction of less than 12 hours' duration. Patients with
      trauma or kidney failure were excluded. Standardized history and physical
      examination data were recorded, as were the results of serial blood sampling for
      S-Mgb, CA-III, and CK-MB at 0, 1, and 3 hours after patient presentation. A
      positive test for the study assays was defined as an S-Mgb concentration of more
      than 110 ng/mL with an S-Mgb/CA-III of 3.21 or higher by receiver operating
      characteristic analysis. Data were analyzed with McNemar's chi 2 test for
      symmetry and confidence intervals (CIs), using the exact method. RESULTS: Thirty
      (12%) of the 251 patients were found to have AMI by World Health Organization
      criteria. Mean time from symptom onset to presentation was 3.2 hours. The use of
      S-Mgb plus S-Mgb/CA-III compared with CK-MB for identification of AMI in patients
      presenting within 3 hours of symptom onset yielded respective sensitivities of
      47.8% versus 17.4% (P = .02); specificities of 98.9% versus 100% (P = NS);
      positive predictive values of 84.6% (95% CI, 54.6% to 98.1%) versus 100% (95% CI,
      39.8% to 100%); and negative predictive values of 93.5% (95% CI, 90.0% to 96.6%)
      versus 90.0% (95% CI, 84.8% to 93.9%). CONCLUSION: S-Mgb in conjunction with S
      Mgb/CA-III was significantly more sensitive than CK-MB yet equally as specific
      for the early diagnosis of patients with AMI.

PMID- 8572444
TI  - Circadian variation in sudden cardiac death: effects of age, sex, and initial
      cardiac rhythm.
AB  - STUDY OBJECTIVE: Previous studies based on data obtained from vital statistics
      records have demonstrated circadian variation in the occurrence of sudden cardiac
      death. The purpose of this study was to examine the effects of age, sex, and
      initial cardiac rhythm on circadian variability in sudden cardiac death. METHODS:
      This study employed a retrospective analysis of the records of adult patients
      with witnessed cardiac arrest who underwent resuscitation in an urban paramedic
      system during a 5-year period. RESULTS: The records of 2,250 consecutive patients
      with witnessed cardiac arrest were reviewed. Spectral analysis was used to
      decompose the data into frequency components. A circadian variation in the
      occurrence of sudden cardiac death was demonstrated, with a low occurrence rate
      between midnight and 6 AM and a 2.4-fold increase between the rate at 6 AM and
      the rate at noon. The same circadian pattern was noted among both men and women,
      among both patients aged 18 to 70 and those older than 70 years, and among
      patients with various initial cardiac arrest rhythms (ventricular tachycardia or
      fibrillation, asystole, and electromechanical dissociation). However, the outcome
      of resuscitation in these patients (ie, the rate of successful resuscitation and
      the rate of survival) did not demonstrate circadian variation. CONCLUSION:
      Witnessed out-of-hospital sudden cardiac death demonstrated circadian variation,
      and this variability was observed regardless of the patient's age, sex, or
      initial cardiac arrest rhythm. The outcome of resuscitation did not show
      circadian variability. These results suggest a common pathophysiologic mechanism
      leading to sudden cardiac death.

PMID- 8572445
TI  - Failure to agree on the electrocardiographic diagnosis of ventricular
      tachycardia.
AB  - STUDY OBJECTIVE: To determine the extent of interobserver agreement in the ECG
      diagnosis of ventricular tachycardia (VT) by using a four-step algorithm and
      three observers. METHODS: Simulated emergency department setting from records of
      an urban university teaching hospital. All ECGs taken in the ED during a 2-year
      period that showed a QRS duration of more than 120 msec and a heart rate faster
      than 110 beats per minute were reviewed. ECGs were categorized as demonstrating
      sinus rhythm (SR), irregular broad-complex tachycardia (I-BCT), or regular broad
      complex tachycardia (BCT). Copies of the BCT ECGs and short clinical histories
      were given to each of three emergency physicians, who used a published, four-step
      algorithm (the Brugada algorithm) to categorize the BCT ECGs as indicating VT,
      indicating supraventricular tachycardia with aberrancy (SVT-A), or indeterminate.
      Interobserver agreement was assessed with the K-statistic. RESULTS: The records
      contained 178 ECGs, 88 of which were SR, 63 I-BCT, and 27 BCT. The 27 BCT ECGs
      were selected for review. The emergency physicians disagreed with each other 22%
      of the time in differentiating VT from SVT-A (K = .58). CONCLUSION: Application
      of the algorithm to actual clinical practice in the ED would probably result in
      the misdiagnosis of a substantial minority of patients having BCT, with
      potentially serious adverse consequences.

PMID- 8572446
TI  - Traumatic hypothermia is related to hypotension, not resuscitation.
AB  - STUDY OBJECTIVE: To determine whether posttraumatic hypothermia is associated
      with hemorrhage or with resuscitation. METHODS: We used a sequential hemorrhage
      resuscitation rat model. Rats were subjected to hemorrhage (30 mL/kg), then 1
      hour of shock, followed by 2:1 crystalloid/blood resuscitation (60 mL/kg) at
      ambient temperature. A control group underwent neither hemorrhage nor
      resuscitation. RESULTS: We recorded core temperature and blood pressure every 10
      minutes. Temperature drop averaged 3.4 degrees C and was fastest during
      hypotensive shock. Rate of temperature change correlated with blood pressure
      (beta = .0102, P < .001), shock phase (beta = .4504, P = .041), and blood
      pressure during shock phase (beta = .0116, P < .001), but not with resuscitation
      phase or with duration of shock or resuscitation. Three of 14 rats died during
      shock, none during resuscitation. An increase in temperature was noted in 1 of 14
      rats during shock and in 7 of 11 rats during resuscitation. CONCLUSION:
      Hemorrhage-associated hypothermia occurs during hypotensive shock, not during
      fluid resuscitation.

PMID- 8572447
TI  - Contaminated wounds: infection rates with subcutaneous sutures.
AB  - STUDY OBJECTIVE: To determine whether buried absorbable subcutaneous sutures
      (BASS) increase the infection rate in irrigated contaminated wounds. METHODS:
      This was a randomized, prospective trial in a rat model, with the histologist
      blinded to treatment group. A single 2-cm dorsal incision was made on each of 30
      anesthetized 250-g Sprague-Dawley rats and inoculated with approximately 10(8)
      organisms of Staphylococcus aureus. After irrigation, 15 wounds were closed with
      running 4-0 nylon transdermal sutures, and 15 were closed with three interrupted
      4-0 coated polyglactin 910 (Vicryl) subcuticular sutures (BASS) and running 4-0
      nylon transdermal sutures. On day 7, wounds were scored on a scale of 0 to 3 in
      six categories: inflammatory infiltrates, fibroplasia and capillary
      proliferation, necrosis, exudates, giant cells, and edema. The possible range for
      the cumulative wound score was 0 (no inflammation) to 18 (severe inflammation and
      infection). RESULTS: The median total wound score in wounds closed with BASS was
      14 (range, 7 to 16); it was 8 (range, 5 to 15) for wounds closed without BASS (P
      = .0004). The subscores for inflammation, necrosis, exudate, and edema were also
      significantly higher in wounds closed with BASS. CONCLUSION: BASS increase the
      infection rate and the degree of inflammation in contaminated wounds, despite
      through irrigation.

PMID- 8572449
TI  - Clinic follow-up from the emergency department: do patients show up?
AB  - STUDY OBJECTIVE: We examined the percentage of outpatient clinic appointments
      kept after referral from the emergency department. Several factors (age, sex, and
      specialty) were examined, to determine their effect on patient compliance.
      METHODS: This study was a retrospective review of the 503 appointments made in
      the orthopedic surgery, plastic surgery, gynecology, and urology clinics at
      Victoria General Hospital (VGH), Halifax, Nova Scotia, Canada, between January 1
      and March 31, 1995, that were referred from the VGH ED. VGH is a 600-bed adult
      teaching hospital with 46,000 emergency visits each year. The patients ranged in
      age from 15 to 92 years. All of the patients were seen in the VGH ED and referred
      to an outpatient clinic in the VGH. RESULTS: Overall, 81.7% of appointments were
      kept. Orthopedic surgery had the best compliance rate (86.7%), gynecology the
      poorest (60.6%). Compliance rates increased with age, and male patients had a
      higher compliance rate than female patients. The average time between ED visit
      and outpatient appointment was 7.9 days, and 59.4% of the patients referred were
      male. CONCLUSION: The compliance rate at VGH is higher than any found in studies
      of similar American hospitals. We determined two main explanations for this
      phenomenon: (1) the ED clerk makes the outpatient clinic appointment before the
      patient leaves the ED and gives the patient a computer printout of the date and
      time of the appointment and a map with the location of the appointment circled,
      and (2) patients do not have to pay for outpatient clinic visits.

PMID- 8572448
TI  - Patient noncompliance with medical advice after the emergency department visit.
AB  - STUDY OBJECTIVE: To determine the correlates of compliance with follow-up
      appointments and prescription filling after an emergency department visit.
      METHODS: This prospective cohort study was undertaken as part of the Emergency
      Department Quality Study evaluation of five urban teaching hospital EDs in the
      northeastern United States. Of 2,757 eligible patients who presented with
      abdominal pain, asthma, chest pain, hand lacerations, head trauma, or first
      trimester vaginal bleeding and were enrolled during 1-month period, 2,315 (84%)
      completed on-site baseline questionnaires. Information about diagnoses,
      socioeconomic status, discharge instructions, insurance status, and primary care
      was obtained from the on-site patient surveys and from reviews of medical
      records. A 76% random sample of patients who completed the questionnaire was
      generated, and 1,386 patients (79% of the sample) were interviewed by telephone
      approximately 10 days after their ED visit to determine compliance with follow-up
      appointments and prescription filling. RESULTS: Of the 1,386 patients interviewed
      at 10 days, 914 (66%) had been discharged from the ED, and 408 (45%) of those
      discharged recalled being advised to take a medication. Fifty of these patients
      (12%) reported that they did not obtain the medication. Significant independent
      correlates of not filling prescriptions were lack of insurance (odds ratio [OR],
      2.4; 95% confidence interval [CI], 1.1 to 5.5) and dissatisfaction with discharge
      instructions (OR, 2.8; 95% CI, 1.2 to 6.4). Two hundred thirty-five (26%) of the
      discharged patients said they were given follow-up appointments and did not have
      an appointment pending at the time of the interview; 77 (33%) of these patients
      reported having missed their appointment. The only significant independent
      correlate of missing follow-up appointments was being given a telephone number to
      call instead of leaving the ED with an appointment scheduled (OR, 3.8; 95% CI,
      1.7 to 8.8). CONCLUSION: Not having an appointment made before leaving the ED was
      an independent correlate of missing follow-up appointments. Lack of insurance and
      dissatisfaction with discharge instructions were independent correlates of not
      filling prescriptions.

PMID- 8572450
TI  - Development of an emergency department-based injury surveillance system.
AB  - STUDY OBJECTIVE: To describe the development of an emergency department-based
      injury surveillance system, to describe the problems encountered, and to briefly
      describe the data output and potential applications. METHODS: Within our
      university-based hospital system and Level I trauma center register, injury data
      currently exist on all ED patients. Over a 1-year period, these data sets were
      linked with our ED log using the hospital identification number and date of
      service as the key merge variables. Elements in our data set included demographic
      information, ED-related variables, and codes for nature of injury and
      circumstances of injury. Data files for 1 month were inspected manually to
      validate the success of the merger. Problems encountered in developing the system
      were summarized. RESULTS: A manual review of 1 month of data files from our
      hospital system, trauma register, and ED log revealed that the records of more
      than 97% (2,802) of 2,878 injury patients seen in our ED had additional data
      attached after the merger. No errors of commission were found, but errors of
      omission occurred. The barriers that were encountered during the development of
      this injury surveillance system are described. CONCLUSION: Hospital data can be
      linked to the ED log to create an injury surveillance system that captures
      valuable information on patients admitted and discharged from the ED.

PMID- 8572451
TI  - Enforcement of drunken driving laws in cases involving injured intoxicated
      drivers.
AB  - STUDY OBJECTIVE: To determine the frequency of driving while impaired (DWI)
      charges among alcohol-intoxicated drivers injured in motor vehicle crashes (MVCs)
      and any differences in the group of those charged compared with those not
      charged. METHODS: We performed a retrospective analysis of linked data from
      medical and judicial sources. Our setting was an urban emergency department of a
      trauma center serving a population of 1 million. We studied consecutive drivers
      injured in MVCs over a period of 15 months who had measured serum ethanol (BAC)
      levels of 100 mg/dL or higher. BAC, Trauma Score (TS), demographics, and crash
      data were linked to court records of charges, outcome, and prior convictions. The
      group of individuals who were charged with DWI were compared with those who were
      not charged. RESULTS: One hundred eighty-seven patients were studied; 53 (28%)
      were charged with DWI, and 32 (17% of total) were convicted. Two (7%) of 29
      patients with severe injuries, 9 (28%) of 32 with moderate injuries, and 42 (33%)
      of 126 with nonsevere injuries were charged (P = .004). Eighteen (16%) of 112
      patients with no prior convictions were charged; 20 (56%) of 36 patients with
      one, 11 (52%) of 21 with two, 3 (25%) of 12 with three, and 0 of 5 with four or
      more prior DWI convictions were charged (P < .001). There were no significant
      differences in BAC, demographics, or other measures between the two groups.
      CONCLUSION: Alcohol-impaired drivers who require ED treatment for injuries
      sustained in an MVC are infrequently charged with DWI. The likelihood of a DWI
      charge diminishes with increasing severity of injury. Repeat offenders are
      charged more often, but the frequency of charges does not increase with
      increasing number of prior DWI convictions.

PMID- 8572452
TI  - State of the journal.

PMID- 8572453
TI  - New approaches to ruling out acute ischemic coronary syndrome in the emergency
      department.

PMID- 8572454
TI  - Emergency medicine in southern Pakistan.

PMID- 8572455
TI  - Effect of a patient's sex on the timing of thrombolytic therapy.
AB  - STUDY OBJECTIVE: We sought to determine whether a patient's sex independently
      influences the interval from emergency department arrival to the initiation of
      thrombolytic therapy in acute myocardial infarction (AMI). METHODS: We conducted
      a retrospective cohort study in two suburban EDs, one at a 929-bed tertiary care
      teaching hospital and the other at a 189-bed community hospital. Only patients
      found to be having an ST-segment-elevated AMI on their first ECG who were treated
      with a thrombolytic agent in the ED were eligible. We excluded patients who
      arrived at the ED after cardiac arrest or with a known AMI. We used as the main
      outcome measure the interval from ED arrival to initiation of thrombolytic
      therapy. Secondary outcome variables included time elapsed before ECG, interval
      between ECG and treatment, and 1-year mortality. RESULTS: Entry criteria were
      satisfied by 328 patients. The 88 women experienced a mean 23-minute delay to
      treatment initiation compared with men (P < .01). This observation is not
      accounted for by age, race, time of day, medical history, sex of the physician,
      type of thrombolytic agent, hospital, or triage category. The longest delays were
      found in women treated by female physicians, although female physicians also
      waited longer than male physicians to administer thrombolytic therapy to men. The
      mean time elapsed before the first ECG was also 6 minutes longer for women (P <
      .01) Women had an increased 1-year mortality rate that was fully explained by
      their advanced age at the time of AMI. CONCLUSION: We infer that a patient's sex
      may play a significant role in the observed delay in treatment for women. Our
      data, coupled with previously published work, strongly suggest a systematic
      negative effect for women in their interaction with the health care system during
      AMI. We suggest that variables other than systems issues affect the time elapsed
      before thrombolytic therapy.

PMID- 8572456
TI  - Emergency medicine in Pakistan.

PMID- 8572457
TI  - Recognition and management of hot liquid aspiration in children.
AB  - Although infrequently reported, aspiration of hot liquid can occur in conjunction
      with upper-body scald burns, leading to acute compromise of the small pediatric
      airway with clinical features similar to those of acute infectious epiglottitis.
      This can be a very difficult problem if subtle signs of impending airway
      compromise are not appreciated. Reported here are four such cases managed over a
      3-year period at a regional pediatric burn center, emphasizing points of history
      and physical examination that facilitate early recognition of this life
      threatening problem. Aspiration of hot liquid should be suspected in children
      with burns in or around the mouth, particularly if there are any subtle signs of
      upper airway edema. If this complication is suspected, immediate endotracheal
      intubation should be performed in those with acute respiratory embarrassment, and
      prompt investigation by direct laryngoscopy in the operating room is appropriate
      in those who have not yet developed overt respiratory distress.

PMID- 8572458
TI  - Use of the scapular manipulation method to reduce an anterior shoulder
      dislocation in the supine position.
AB  - We report the successful use of the scapular manipulation method to reduce an
      anterior shoulder dislocation in a multiply traumatized patient in the supine
      position. We discuss the treatment options for multiply traumatized patients with
      anterior shoulder dislocations in whom cervical spine injury is a possibility.
      Although larger patient studies are necessary for confirmation, we show that in
      this particular case the scapular manipulation technique was safely employed. To
      our knowledge, this is the first reported case of use of the scapular
      manipulation method with the patient in the supine position.

PMID- 8572459
TI  - Thrombotic thrombocytopenic purpura presenting as a sudden headache with focal
      neurologic findings.
AB  - We report a case of thrombotic thrombocytopenic purpura presenting as a sudden
      headache with associated neurologic deficits. The diagnosis of this rare disorder
      is discussed, with special attention given to a potential pitfall in evaluation
      and treatment--platelet transfusion.

PMID- 8572460
TI  - [Consensus conference. Follow-up of patients surgically treated for stage I
      melanoma. Paris, France, 30 March 1995].

PMID- 8572461
TI  - [Consensus conference. Follow-up of patients surgically treated for stage I
      melanoma].

PMID- 8572462
TI  - [Professional practice in stage I melanoma. A national survey of dermatologists].

PMID- 8572463
TI  - [Modalities of follow-up after excision of stage I melanoma: practice survey in
      hospitals].

PMID- 8572464
TI  - [Prognostic factors of stage I melanoma: non histological factors].

PMID- 8572465
TI  - [Histological risk factors of isolated primary melanoma].

PMID- 8572467
TI  - [Usefulness of an initial evaluation in stage I melanoma].

PMID- 8572466
TI  - [Detection methods of local, regional and distant recurrences of melanoma].

PMID- 8572468
TI  - [After excision of primary melanoma should an initial evaluation be performed?
      Point of view of a French dermatologist].

PMID- 8572469
TI  - [Monitoring of patients with stage I melanoma after excision of the primary
      tumor].

PMID- 8572470
TI  - [Methods of detection of recurrence, which method, how often and for how long?].

PMID- 8572471
TI  - [After diagnosing melanoma in a patient: evaluation of risks of second melanoma
      and melanoma in the family].

PMID- 8572472
TI  - [When, how and which patients should be screened for second melanoma?].

PMID- 8572473
TI  - [Adjuvant therapy of surgically removed stage I melanoma].

PMID- 8572474
TI  - [Are there special therapeutic methods recommended by some physicians for the
      management of stage I melanoma?].

PMID- 8572475
TI  - [Future of malignant melanoma. New morphologic techniques; hormone receptors].

PMID- 8572476
TI  - [Future of malignant stage I melanoma. Immunology and immunotherapy].

PMID- 8572477
TI  - [In a patient, surgically treated for isolated primary melanoma, what is the risk
      of recurrence? How to evaluate this risk?].

PMID- 8572478
TI  - [After excision of primary stage I cutaneous melanoma, is an initial evaluation
      necessary?].

PMID- 8572479
TI  - [What are the methods for the detection of recurrent melanoma? What is their
      value? Should they be implemented? Which ones and how often?].

PMID- 8572480
TI  - [Multiple primary melanoma and familial melanoma. Risk evaluation and screening
      tests. How to evaluate the risk of developing a second melanoma? In what family?
      Should screening methods be implemented? Which ones and why?].

PMID- 8572481
TI  - [Are there specific follow-up modalities recommended in the treatment of stage I
      melanoma?].

PMID- 8572483
TI  - [Predisposing factors in cutaneous reactions to drugs].

PMID- 8572482
TI  - [What are expected improvements in the follow-up and treatment of stage I
      melanoma?].

PMID- 8572484
TI  - [Lymphoma with skin manifestations in HIV infection: 8 cases].
AB  - INTRODUCTION: Cutaneous lymphomas occurring in HIV infection are a rare disease.
      Most of them are high grade lymphomas with fulminant course and poor prognosis.
      OBJECTIVE: Evaluate clinical and histological aspects as well as immunophenotype
      and evolution of these lymphomas. PATIENTS AND METHODS: Eight patients with HIV
      infection were studied between 1992 and 1994. The clinical and histological
      features were reviewed by the members of the French Study Group for Cutaneous
      Lymphomas. Staging procedures for lymphomas were performed in 7/8 patients.
      RESULTS: Seven non epidermotropic lymphomas and one mycosis fungoides were
      reviewed. Patients were male (6 cases) and female (2 cases); their mean age was
      45 years (27-63). The mean level of CD4 T cells/mm3 was 141 (20-380). Only one
      patient presented with extracutaneous lesions. These lesions were similar to
      seronegative patients, but unusual features were observed in two cases.
      Histological classification showed high grade lymphomas in 6/8 cases. The
      immunophenotype was: T-cell lymphoma in 4 cases, B-cell lymphoma in 3 cases; it
      could not be determinated in one case. Six patients died. The median of survival
      is 8 months in this series. DISCUSSION: Our series confirms the predominance of
      high grade lymphomas presenting in the skin. The T-cell phenotype is more
      frequent. The onset of a cutaneous lymphoma has a poor prognosis in HIV
      infection. Most of our patients had localised disease at presentation.
      Therapeutic management of these lymphomas must be codified.

PMID- 8572485
TI  - [Bacterial dermo-hypodermatitis in adults. Incidence and role of streptococcal
      etiology].
AB  - INTRODUCTION: The frequency of bacterial dermohypodermal infections would appear
      to be increasing in western countries, particularly severe necrotizing forms.
      PATIENTS AND METHODS: We attempted to determine: (1) the incidence of the two
      most well-defined forms of bacterial dermohypodermal infections (erysipelas and
      necrotizing fasciitis) in a retrospective study of hospitalized cases seen over a
      period of 13 years in the Limoges University Hospital and (2) the role of
      streptococci as causative agents in bacterial dermohypodermal infections in the
      adult by collecting bacteriological data in 174 cases of erysipelas and 31 cases
      of necrotizing fasciitis. RESULTS: This retrospective analysis confirmed that the
      annual incidence of erysipelas was constantly increasing over the study period
      (1978-1991) while the annual incidence of necrotizing fasciitis was much lower
      and more constant. The two incidence curves were not parallel. Bacteriology,
      detection of streptococci (groups A, B, C or G) in skin specimen was better with
      direct immunofluorescence (64 p. 100) than with latex agglutination (47 p. 100)
      or classic culture techniques (28 p. 100) for erysipelas. Streptococci were
      determined to be the causative agent in 79 p. 100 (137/174) of the cases of
      erysipelas using at least one of the 3 bacteriological tests and/or serology.
      Group A streptococci predominated (67 p. 100 of the cases). For necrotizing
      fasciitis, streptococci was identified with classical culture technique, latex
      agglutination and/or serology in 12/131 cases (39 p. 100), again with a group A
      predominance (7 cases). In the other cases, multiple microbial flora (12 cases)
      were found including Staphylococcus aureus (3 cases) and Serratia liquefaciens (1
      case). CONCLUSION: These results show that streptococci (group A predominantly
      and group G to a lesser extent) were the major, though not exclusive, causative
      agents in bacterial dermohypodermal infections in the adult, including
      necrotizing forms.

PMID- 8572486
TI  - [Cutaneous granulomatous lesions in congenital immune deficiencies. 5 cases].
AB  - INTRODUCTION: Cutaneous granulomatous lesions rarely occur in primary
      immunodeficiency syndromes. CASES REPORTS: We observed chronic granulomatous
      lesions on the skin of 5 children with inborn immunodeficiency syndromes. The
      deficiency was of the mixed type in all 5 cases and included major
      hypogammaglobulinaemia in 4. Erythemato-squamous infiltrated plaques were found
      in 4 children and erythematous nodules in the fifth. Extra-cutaneous lesions
      (cavum and rectocolon) occurred in 2 children. Search for an infectious cause was
      negative. Anti-tuberculosis drugs were tried in 3 children as a test regimen and
      were ineffective. Systemic corticosteroids gave major clinical improvement in 2
      children. DISCUSSION: Several pathogenic processes have been hypothesized to
      explain the development of granulomatous lesions in immunodeficiency syndromes.
      The action of an unknown infectious agent has been suspected. An intrinsic
      anomaly in immune function regulation, particularly in a disequilibrium in the
      complex cytokine network controlling the formation of granulomas could also be
      involved. Systemic corticosteroid therapy appears to be effective but must be
      given with caution in these patients with immune deficiency.

PMID- 8572487
TI  - [Normolipemic plane xanthoma, monoclonal gammopathy, anti-lipoprotein activity,
      hypocomplementemia].
AB  - INTRODUCTION: Normolipaemic plane xanthomatosis is classically associated with a
      monoclonal gammapathy. CASE REPORT: We observed this association in a 69-year-old
      woman. This case was particular since anti-lipoprotein activity due to a
      monoclonal IgG immunoglobulin was found in the serum with abnormal complement
      fractions. The paraproteinaemia remained stable after a 2-year follow-up.
      CONCLUSION: This association is remarkable. The anti-lipoprotein activity of the
      monoclonal protein should be emphasized in light of the immunological processes
      involved in the pathogenesis of this association.

PMID- 8572489
TI  - [Cutaneous necrosis caused by hydrofluoric acid].
AB  - INTRODUCTION: Hydrofluoric acid is a fluoride-substituted compound used in the
      chemical industry. Burns and hypocalcaemia result from ingestion or contact with
      the skin or mucosal membranes. We observed burns and skin necrosis on the hands
      after home use of low-concentration hydrofluoric acid. CASE REPORT: A 57-year-old
      woman consulted in February 1994 for oedema, erythema and very painful burns of
      the palms of both hands. The day before, she had used a home-made furniture
      cleanser containing 5 p. 100 hydrofluoric acid. At admission, calcium and
      radiography of the two hands were normal. She was given a topical application of
      5 p. 100 calcium chloride. The clinical course was favourable with squamation of
      both palms then necrotic lesions of the pulp on the 1st, 2nd and 3rd fingers.
      DISCUSSION: Such exposure in a household situation is unusual. Hydrofluoric acid
      has two dangerous mechanisms of action. First it is a caustic substance producing
      late-onset burns and secondly hypocalcaemia results from precipitation of
      insoluble calcium fluoride. The risk of hypocalcaemia is greatest when a large
      area of the skin is exposed. Prognosis depends on early treatment based on
      prevention of hypocalcaemia by abundant washing of the teguments and permanent
      application of a 5 p. 100 calcium gluconate solution associated with local skin
      treatments. Careful follow-up is required with regular calcium chemistries.

PMID- 8572488
TI  - [Disseminated cutaneous neurilemmomatosis].
AB  - INTRODUCTION: Neurilemmomatosis is a rare, non-inherited disease which has
      several features similar to type I neurofibromatosis. CASE REPORT: A 30-year-old
      man had more than 300 cutaneomucosal tumours. Most were sessile and of firm
      consistency on normal coloured skin. Histology reported masses of fusiform dermal
      cells S100 protein (+), NSE (-), actin (-). The cells had a polygonal
      ultrastructure with fine ramifications. Neurilemmomatosis (schwannomatosis) was
      diagnosed. No neurological or systemic disorder could be detected. The most
      bothersome tumors were destroyed. DISCUSSION: This is a typical anatomoclinical
      presentation of cutaneous neurilemmomatosis. This exceptional state raises the
      problem of differential diagnosis and nosological distinction from von
      Recklinhausen's disease. A characteristic feature in this case was the total
      absence of any malformation or associated tumour, notably neurological tumours.
      To our knowledge, this is the only documented case of disseminated
      neurilemmomatosis strictly limited to the skin.

PMID- 8572490
TI  - [Hypersensitivity syndrome caused by dapsone. Transient circulating clone T].
AB  - INTRODUCTION: Hypersensitivity is a rare side-effect of dapsone. The most
      complete clinical presentation associates papulous exanthema, lymph node
      enlargement, liver cell failure and an increase in mononuclear and eosinophil
      counts. CASE REPORT: A 45-year-old woman developed hypersensitivity to dapsone
      when this drug was used to treat corticoid-dependent asthma. A transient
      circulating clone T was demonstrated by Southern blot during the acute phase. The
      clinical manifestations and laboratory findings returned to normal under systemic
      corticosteroid treatment. When corticoids were tapered off, hypersensitivity
      reactions began to progress again. DISCUSSION: Transient circulating clone T, as
      observed here, emphasizes the importance of close surveillance and long-term
      follow-up in drug-induced hypersensitivity syndromes.

PMID- 8572491
TI  - [Ultrastructural study of hereditary benign telangiectasia. Differential
      diagnosis from Osler Rendu disease].
AB  - INTRODUCTION: There are two hereditary forms of primary telangiectasia with a
      totally opposite prognosis. In Rendu-Osler disease, also called hereditary
      haemorrhagic telangiectasia, there is a major risk of severe haemorrhage in
      adults. In benign hereditary telangiectasia there is no such risk. CASE REPORT:
      We report two brothers who were diagnosed as having Rendu-Osler disease. Under
      standard electron microscopy, a biopsy of a telangiectasia taken from the right
      arm pit showed that the vessels of the superficial reticular derma were dilated
      with thick walls but no dehiscences as in Rendu-Osler disease. DISCUSSION: This
      ultrastructure explains why there had been no haemorrhages in our two cases and
      favoured a diagnosis of hereditary benign telangiectasia.

PMID- 8572492
TI  - [Cutaneous pseudolymphoma during treatment of rheumatoid polyarthritis with low
      dose methotrexate].
AB  - INTRODUCTION: Over the last three years, there have been over twenty case reports
      of lymphoma in patients given low-dose methotrexate for rheumatoid arthritis. We
      observed the first case of cutaneous pseudolymphoma. CASE REPORT: A 56-year-old
      man had been treated with methotrexate (15 mg/day) for 6 years due to rheumatoid
      arthritis. He developed three isolated papulonodular ulcerations on the limbs.
      The histology and immunohistochemical examinations demonstrated T and B
      lymphoplasmocyte infiltration without epidermotropism nor destruction of the
      annexes. Immunolabelling for anti-Epstein-Barr virus was negative. There was a
      IgG lambda type monoclonal hypergammaglobulinaemia, Bence-Jones proteinuria and
      an increase in beta 2-microglobulin. The thoracoabdominal scan, bone marrow
      biopsy and gallium scintigraphy were normal. There was no sign of a Gougerot
      Sjogren syndrome nor of a Felty syndrome. The skin lesions and the Bence-Jones
      proteinuria disappeared rapidly after withdrawal of methotrexate. There has been
      no recurrence with a follow-up of 16 months. DISCUSSION: The diagnosis of
      pseudolymphoma was retained on the basis of the clinical features, the
      histological and immunohistochemical evidence and especially on the clinical
      course after methotrexate withdrawal, i.e. spontaneous regression of the lesions
      within 3 weeks. A similar course has been observed in three cases of lymphocyte
      proliferation suggesting that this immunosuppressor would be the most probable
      causative agent. Lymphocyte proliferation, mainly B-cell lymphomas in
      haematopoietic organs occurring under methotrexate administration have occurred
      mainly in patients with rheumatoid arthritis. Three cases have also been
      described in patients with dermatomyositis, but none have been reported in
      patients with psoriasis. This would suggest that cofactors involved in these
      autoimmune diseases could also have an effect: immunodepression, potentialization
      due to associated treatment (corticosteroids), Epstein-Barr virus... CONCLUSION:
      Data on these observations should be combined in order to analyse the question of
      the safety of low-dose methotrexate in these patients.

PMID- 8572493
TI  - [Cutaneous localization of T-cell prolymphocytic leukemia].
AB  - INTRODUCTION: T cell prolymphocytic leukemia (T PLL) is a rare variant of mature
      lympho-proliferative disorder. The main physical sign is a gross splenic
      enlargement contrasting with no enlargement of lymph nodes. Skin involvement is
      found in 30 p. 100 cases. Twenty-one cases of cutaneous lesions of PLL have been
      reported, mainly with T PLL, only 2 cases of B PLL: Clinical lesions are
      polymorphous; histology shows a dermal prolymphocytic infiltrate. The main
      cytogenetic abnormalities are: translocation (14; 14) (q11; q32), inversion of
      chromosome 14 (q11; q32), isochromosome 8q. CASE REPORT: We report a case of an
      87-year-old patient presenting a T cell prolymphocytic leukemia CD4+ with
      specific papular lesions of the back. Electron microscopy showed typical
      prolymphocytes and cytogenetic studies showed a tendency to polyploidy, with the
      lost of chromosome 14, translocation 8-22 and inversion of chromosome 13. After
      12 months of treatment with a combination of chloraminophen and prednisone the
      patient was in partial remission and the cutaneous lesions disappeared.
      DISCUSSION: This case is rare and the patient has an unusual long survival (mean
      survival is 7 months). Contrary to the other hematologic disorders, cutaneous
      involvement does not change the prognosis of T PLL:

PMID- 8572494
TI  - [Cutaneous transformation of chronic lymphoid leukemia into immunoblastic
      lymphoma. Cutaneous manifestation of Richter syndrome].
AB  - INTRODUCTION: Richter's syndrome is a large-cell lymphoma occurring in patients
      with chronic lymphoid leukaemia (CLL). It is rarely limited to cutaneous
      locations. We report the case of a 61-year-old patient with CLL who developed
      multiple skin lesions due to immunoblastic lymphoma. CASE REPORT: Six years after
      onset of CLL controlled by chloraminophen, a tumoural syndrome developed and was
      treated by chemotherapy. A papulonecrotic cutaneous eruption was then observed on
      the face, the presternal area and then on the fingers. Skin biopsy revealed large
      cell CD20+ CD30+ immunoblastic lymphoma. Polymerase chain reaction on the heavy
      chain immunoglobulins showed a band with the same size in the skin biopsy and in
      the circulating cells. No transformation was found in lymph node and bone marrow
      biopsies. The lesions disappeared after 4 treatments with VP16, cysplatin and
      methylprednisolone. CLL was again stabilized after the first chemotherapy
      sessions. DISCUSSION: Richter's syndrome is rarely discovered due to skin
      lesions. There have only been 4 similar cases reported in the literature. The
      clinical presentation of the lesions is insufficient to distinguish them from
      manifestations of CLL. Histological examination of the biopsy is required to make
      the diagnosis of high grade lymphoma. Prognosis is usually poor after discover of
      this type of lymphoma. This is the first observation of Richter's syndrome
      revealed by a skin lesion in which polymerase chain reaction suggested that the
      skin lymphoma and the CLL cells came from the same B clone.

PMID- 8572495
TI  - [Sheep wool granuloma].
AB  - INTRODUCTION: We report the unusual case of cutaneous foreign body granulomas
      provoked by sheep wool. CASE REPORT: A 45-years old woman presented within one
      year two episodes of a papular eruption on her neck and limbs. She was working as
      a farmer's wife and each episode occurred after preparing the ewes for coupling.
      She had to keep a tight hold on the ewes while the farmer introduced warm and
      moist compresses in the genitals of the animals. Each diseased skin area was
      closely related to the tight contact with the sheep's wool and on histological
      slides each granuloma was centered by a tiny ply of wool. DISCUSSION: This
      foreign body reaction may be compared to the trichogranulomas of hairdressers. In
      sheep breeders this occupational practice is very usual and one may wonder why
      this type of reaction seems so rare.

PMID- 8572496
TI  - [Inguinal mastocytosis with histiocytic infiltrate].
AB  - INTRODUCTION: The diagnosis of mastocytosis is usually not difficult in cases
      with typical skin lesions. Intertrigo is exceptional. CASE REPORT: An 83-year-old
      patient developed inguinal intertrigo bilaterally. The lesions contained
      maculopapulous elements without Darier's sign. The histology examination revealed
      a mixed mast cell infiltration predominated by histiocytes. The ultrastructure
      confirmed the diagnosis of cutaneous mastocytosis. No extension was observed.
      DISCUSSION: Skin folds are rarely involved in infiltrating diffuse mastocytosis.
      Two cases have been reported in the literature including one doubtful case.
      Mastocytosis should thus be included in the possible diagnoses in patients with
      macupopapulous intertrigo. In addition, the mastocytic and histiocytic
      polymorphism observed here is rare.

PMID- 8572497
TI  - [Eruptive nevus in the course of Lyell syndrome].
AB  - INTRODUCTION: Eruptive nevus have been described after severe bullous cutaneous
      adverse drug reactions. We report herein a berloque-like nevus extension after
      toxic epidermal necrolysis. CASE REPORT: A 23 year-old woman was hospitalized for
      toxic epidermal necrolysis. A blister was in contact with a nevus. Four months
      after healing, extension of the nevus was seen on the blister area. DISCUSSION:
      During toxic epidermal necrolysis and healing: 1) cytokines and growth factors
      are produced favouring nevocytes proliferation; 2) macromolecules are exposed on
      the wound bed; 3) adhesion molecules are expressed on nevocytes, restricting cell
      migration on exposed macromolecules. Interaction between matrix macromolecules
      and adhesion molecules could explain the limitation of nevus extension.

PMID- 8572498
TI  - [Case for diagnosis. Camptodactyly].

PMID- 8572499
TI  - [Case for diagnosis. Bejel].

PMID- 8572500
TI  - [Cutaneous reactions to external orthopedic materials].

PMID- 8572501
TI  - [Local treatments of AIDS-related Kaposi disease].

PMID- 8572502
TI  - [When and why assay neutrophil cytoplasmic antibodies in dermatology?].

PMID- 8572503
TI  - [Immunologic relevance of malonic dialdehyde].
AB  - Free radicals are involved in many physiological and pathological processes,
      including oxidation of polyunsaturated fatty acids, i.e. lipoperoxidation. Among
      the different by-products of this lipoperoxidation, malonic dialdehyde (MDA) has
      been one of the most studied. It reacts with the primary amino groups of
      biological molecules, especially those of proteins, with formation of 1-amino-3
      imino-propene (AIP) bridges. Studies undertaken in our laboratory about the
      immunological relevance of MDA have first shown the existence of antibodies
      (AcAIP) recognizing epitopes containing AIP bridges, and reacting specifically
      with MDA-modified proteins but not with the corresponding native ones. These
      antibodies occur even under physiological conditions, independently of any
      disease or any stimulation induced by antigen injection. However, their seric
      level may be modified in pathologies involving an increased lipoperoxidation
      and/or an inflammatory process (cardiovascular pathology, diabetes, alcoholism).
      Injections of a MDA-protein adduct to rabbits or mice stimulates AcAIP
      production, even if the protein contained in the adduct in an autologous one, but
      such injections may also result in production of other antibodies. Other results
      obtained in our laboratory indicate that AcAIP are involved in elimination of
      senescent or lipoperidized erythrocytes, and probably also in discarding other
      cells having undergone oxidative stress, at least the circulating ones. The
      physiological and pathological implications of MDA and AcAIP have lead us to
      formulate hypotheses about their more general role within the immune system, and
      to try to situate them in this system. Of course, these hypotheses remain to be
      assessed by further experimentations.

PMID- 8572504
TI  - [Revealing hair].
AB  - Hair testing is an effective method for identifying chronic drug abusers. The
      procedure involves a decontamination step, acid hydrolysis in presence of
      deuterated internal standards, liquid-liquid extraction and analysis by gas
      chromatography coupled to mass spectrometry. Hair analysis has a wide window of
      detection ranging from months to years and provides informations concerning the
      severity and pattern of an individual's drug use.

PMID- 8572505
TI  - [Characterization of lorazepam and oxazepam by the thermal behavior of their
      degradation product].
AB  - Lorazepam and oxazepam are benzodiazepine which differ by the presence, or not,
      of chlorine atom on the phenyl ring. These molecules are able of chemical and
      thermal degradation with water intramolecular elimination between hydroxy and
      amine functional group and formation of carboxaldehyde quinazoline. These
      substances characterise lorazepam and oxazepam by their thermal behaviour and
      melting temperature by heating and cooling cycles.

PMID- 8572506
TI  - [Imidazo(2,1-b)thiazole XII derivatives. Synthesis and research of immunoactivity
      in vitro on human T lymphocyte of 3-aroylmethyl and 2-aroyl-3-methyl(aryl)-5,6
      dihydroimidaz o(2,1-b)thiazoles].
AB  - To estimate the influence of aryl group position on the immunostimulant
      properties of imidazo[2,1-b]thiazole derivatives, several compounds were obtained
      and tested, versus tetramisole hydrochloride, on the mobilisation of CD2 receptor
      by human T lymphocyte. The synthesis use the action of monobrominated beta
      diketones on the 2-mercaptoimidazoline. So, 1-aryl-4-bromobutane-1,3-diones lead
      to 3-aroylmethyl-5,6-dihydroimidazo[2,1-b]thiazoles 4. Same, 1-aryl-2-bromobutane
      1,3-diones and 1,3-diaryl-2-bromopentane-1,3-diones give respectively 3-aroyl-2
      methyl-5,6-dihydroimidazo[2,1-b]thiazoles 5 and 3-aroyl-2-aryl-5,6
      dihydroimidazo[2,1-b]thiazoles 6. Better yields are obtained when the reaction
      presents two steps. The first one, realized in acetone at room temperature, leads
      to an intermediate S-substituted 4,5-dihydroimidazole which, in second step, is
      cyclized in imidazo[2,1-b]thiazole compound via an unisolated carbinolamine. This
      one explains the univocal formation of 5 derivatives and the feasible blending in
      case of 6. The immunoactivity of several imidazothiazoles 4, 5 and 6 is lower
      that them of 6-aryl substituted compounds and particularly that the levamisole
      which is the reference product in this series.

PMID- 8572507
TI  - [Doctorates in medicine and pharmacy].
AB  - Pharmacists had to wait until the Delong Act in 1979 to obtain a diploma of
      professional practice giving them the title of doctor. Since 1898, some of them
      could be called "Doctor of Pharmacy", but this title was neither a university
      degree nor a diploma of professional practice. A state doctorate of pharmacy was
      created in 1939 and replaced in 1977 by the doctorate of pharmaceutical sciences
      which was suppressed in 1984, like all other doctorates as university degrees.
      With the present reform, the doctorate of medicine, which was both a university
      degree and a diploma of professional practice, has only kept this latter
      qualification as "state diploma of doctor of medicine", like the pharmacists new
      diploma of professional practice. Physicians and pharmacists can now only obtain
      the highest university grade with the "doctorate" created in 1984. The conditions
      of obtention are indicated.

PMID- 8572508
TI  - [Bioavailability in rats of tyrosine, micronized tyrosine and tyrosine beta
      cyclodextrin inclusion administrated by oral route].

PMID- 8572509
TI  - [Leukocyte depletion of red cell concentrates: the example of PAGGS-Sorbitol
      concentrates].

PMID- 8572510
TI  - Reconstructive microsurgery of the hand.

PMID- 8572511
TI  - Training and certification of hand surgery as an independent specialty.

PMID- 8572512
TI  - An approach to the management of radial longitudinal deficiency.
AB  - This paper describes an approach to the management of radial longitudinal
      deficiency. Early treatment includes manipulation and splintage prior to
      realignment of the carpus on the forearm. Twelve patients are presented in which
      a comparison is made between centralisation and radialisation surgical
      techniques. Preoperative distraction allowed radialisation without excision of a
      part of the carpus in five out of six patients. In contrast, centralisation with
      carpal excision was necessary in 5 out of 6 patients not treated by preoperative
      distraction. It remains to be seen whether radialisation is a superior procedure
      to centralisation in the longer term. However, radialisation in theory allows
      greater protection for the distal ulnar physis, maintains maximal length, and
      allows optimal wrist motion. Late treatment of radial longitudinal deficiency
      includes techniques of bone lengthening and correction of radial deviation
      deformity. Three cases are presented in which the Ilizarov technique was used to
      lengthen the forearm and to correct deformity. The complications of forearm
      lengthening are high but these techniques do allow significant correction of
      deformity.

PMID- 8572513
TI  - Microsurgical reconstruction of sensory skin.
AB  - Loss of sensory function is a severe impairment for the hand which loses a lot of
      its dexterity, becomes "blind" if not guided by sight and is susceptible to
      burns, wounds and infections. Nerve repair by sutures or grafts is the preeminent
      operation if the condition of the skin is good. When skin is damaged, various
      sensory flaps (both free microvascular and local pedicle) may be used. Island
      flaps from the pulp of another digit give inconsistent results. Sensory flaps
      from the back of the index finger to the thumb give a fair two-point
      discrimination. Free microvascular flaps from the pulp or the web of the hallux
      or from two or even three toes are safe and good operations which restore both
      perfect skin coverage and excellent sensory function with good two-point
      discrimination. The damage at the donor site is well tolerated. When previous
      operations have covered the digit or the hand by means of non-sensory skin,
      direct neurotization of this skin is possible. Research has been done in animals
      showing the formation of free endings inside the neurotized skin. Rehabilitation
      of the previously existing sensory corpuscles is even possible. Our series
      includes 12 island flaps from the pulp, 19 pedicle flaps from the dorsum, 17
      homodigital reverse flow flaps, 38 different types of free neurovascular flaps
      from the foot and 3 direct sensory neurotization.

PMID- 8572514
TI  - The role of microsurgery and free tissue transfer in the reconstruction of the
      paediatric upper extremity.
AB  - A review of the role of microvascular autotransplantation in reconstructive
      surgery of the paediatric upper limb is presented. Such techniques bring
      versatility to reconstruction of the upper limb that has previously not been
      available. In particular they offer the opportunity for transplantation of skin
      flaps in one stage, and the transplantation of vascularised joints and growth
      centres. Most importantly however, they offer the opportunity to reconstruct
      digits by transplantation of homologues from the foot. The surgical techniques
      are complex but reliable, and we place emphasis upon the value of the specialised
      care team and the counselling of families and patients. This also has the benefit
      of minimising the morbidity of these procedures to a level that is equal to or
      better than their conventional alternatives.

PMID- 8572515
TI  - Flap reconstruction in the upper limb.
AB  - The introduction of the free flap and the regional fasciocutaneous flap has added
      to the methods of skin defect coverage in the upper limb and avoids the
      disadvantages of conventional flaps. This paper describes the features and
      indications of regional axial pattern flaps and free flaps for upper limb skin
      defects. They can be categorised into flaps in the ipsilateral upper limb and
      flaps from out of the upper limb. Flaps in the upper limb include the lateral arm
      flap, the radial forearm flap, the posterior interosseous artery flap, the dorsal
      metacarpal artery flap, and the digital artery flap. Flaps from out of the upper
      limb comprise the latissimus dorsi myocutaneous flap, the scapular flap, the
      groin flap and the hemipulp flap. Criteria for flap selection include the
      patient's age and health, the condition of the skin defects, the location and
      size of the defects and damage of the deep structure, the patient's cosmetic
      demand, the surgeon's technical skill and the facilities in the operating room.

PMID- 8572516
TI  - Current concepts of replantation.
AB  - The rapidly expanding microsurgical knowledge and technology along with a growing
      experience in replantation has led the way to new concepts of management that
      have become essential in the progressive treatment for these complex injuries.
      Appropriate patient selection, proper modes of limb transportation, injury
      assessment, surgical technique, and postoperative care are all key components to
      successful recovery and restoration of function. As the ability to restore
      vascular flow to amputated digits, hands, and limbs has advanced, critical
      evaluation of the potential extent of recovery in comparison to amputation
      revision is imperative. This article discusses the current ideas of the
      perioperative treatment for replantation with specific attention directed towards
      these evolving issues.

PMID- 8572517
TI  - Combined free flap, Ilizarov lengthening and prosthetic fitting in the
      reconstruction of a proximal forearm amputation--a case report.
AB  - A composite free latissimus dorsi musculocutaneous flap combined with Ilizarov
      lengthening was used in the resurfacing of the elbow and the reconstruction of
      the forearm following a very proximal below elbow amputation with soft tissue
      degloving to the level of the mid arm. The free flap provided gliding soft tissue
      to the elbow joint, and the deep fascia and muscle components of the flap were
      contoured round the bony stump so as to allow bone transport within the soft
      tissue envelope. The lengthening achieved was 14 cm with no bone resorption at
      the end of the stump. The reconstructed forearm, with a well-contoured stump
      covered with durable and adherent soft tissue, allowed the fitting of a forearm
      based lightweight hand glove prosthesis. With the combined modalities of
      microsurgical free tissue transfer, the Ilizarov method of slow distraction and
      prosthetic fitting, we were able to achieve restoration of both form and function
      in a difficult case of major upper extremity amputation.

PMID- 8572518
TI  - Sequential flap transplantations for total reconstruction of avulsion amputation
      of the fingers--a case report.
AB  - The degloved and partially amputated ring and middle fingers of the left hand of
      a 40-year-old male was re-surfaced with two flaps transplanted sequentially: the
      toe wrap-around flap and the reversed pedicled metacarpal flap. Sensate and non
      glabous skin was restored to the tip of the finger stumps as well as a supple
      full thickness reconstruction of the web space was achieved.

PMID- 8572519
TI  - Osteocutaneous lateral arm flap in hand reconstruction.
AB  - Complex injuries of the hand often have severe soft tissue damage and associated
      intercalary segmental or distal loss of bone. Bone grafting to restore the
      skeletal scaffold is essential for soft tissue reconstruction. With a poor
      vascular bed, non-vascularised free bone grafts are not desirable. We describe 14
      cases of vascularised humeral bone grafting for these difficult reconstructions.
      The bone was harvested as an osteocutaneous lateral arm flap. Constant osseous
      branches from the main pedicle of the posterior radial collateral artery which
      travel along the lateral intermuscular septum to the bone were preserved. Humeral
      bone grafts as a composite with the lateral arm flap are able to provide 1.5 x 10
      cm of well vascularised bone for hand reconstruction. All 14 flaps survived and X
      rays of the graft at 3 to 6 months showed consolidated bony union with little or
      no bony resorption.

PMID- 8572520
TI  - Comparative pathoanatomy of the Asian and Caucasian trapeziometacarpal joint.
AB  - The frequency and distribution of idiopathic osteoarthritis (OA) in the upper
      extremity has been observed to vary considerably among different races. This
      study seeks to investigate the prevalence of trapeziometacarpal OA and
      differences in pathologic anatomy in comparable populations of Caucasian and
      Asian peoples. Sixty-one postmortem Japanese, Chinese and Indian specimens were
      examined for integrity of both the stabilising soft tissue structures and
      articular surfaces. Chondromalacia and eburnation were assessed by location in
      the joint relative to previously described patterns of disease in Caucasian
      specimens. Among 35 Japanese specimens, 23 (66%) were found to have completely
      normal joint surfaces, 5 (14%) had chondromalacia limited to the dorsal surfaces,
      2 (6%) had chondromalacia on the volar surfaces, and 5 (14%) exhibited eburnation
      consistent with advanced degenerative disease. A similar distribution was noted
      for the 22 Chinese specimens. When present, the pattern of arthritic disease was
      identical to that seen in Caucasian joints; eburnation of surfaces was only seen
      in the volar compartment and dorsal joint cartilage was typically spared.
      Detachment of the volar beak ligament was evident in all joints with eburnation,
      and degeneration of the metacarpal insertion was present in specimens with volar
      chondromalacia. The concavoconvex configuration of the joint surfaces was more
      shallow in Japanese and Chinese specimens than comparable Caucasian joints. A
      similar study of Caucasian joints demonstrated only 25% with normal articular
      surfaces, 10% with dorsal chondromalacia as a lesion indicative of physiologic
      aging, 15% with volar chondromalacia as a prearthritic progressive lesion, and
      50% with eburnation indicative of end-stage arthritic disease. Based upon the
      study of postmortem material, the anatomical prevalence of trapeziometacarpal
      joint osteoarthritis is considerably less in the Japanese and Chinese than in the
      Caucasian race.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8572521
TI  - Vascularised flexor tendon grafts.
AB  - In densely scarred digits, tendon reconstruction fails because of paucity of
      blood supply. This inevitably leads to adhesion formation and failure of gliding.
      Staged tendon grafting with silicone spaces can improve results but does not
      ameliorate the essential problem of reduced vascularity and may indeed worsen it.
      Tendon grafts can be implanted with their own living sheaths as free or pedicled
      vascularised transfers from the foot or forearm to either extensor or flexor
      sites in the hand. These mesenteric tendons with their fascial or synovial
      sheaths intact and vascularised by adjacent vascular pedicles include the
      extensor hallucis brevis and longus or the extensor digitorum communis on the
      dorsalis pedis system, the palmaris longus on the radial arterial system, the
      sublimus tendons of the ring and little fingers on the ulnar arterial system as
      well as the extensor indicis on the second metacarpal arterial system. These
      tendon grafts can be inserted into the intact or reconstructed tunnel systems of
      the digit and repaired proximally and distally to the tendon remnants. Gliding is
      enhanced although limitations still potentially occur at the proximal tendon
      junctions.

PMID- 8572523
TI  - Upper limb digital replantation and revascularisation in children.
AB  - Amputations in children are not common and experience in microvascular digital
      replantation in children is not extensive. We report our experience of ten
      digital replantations in eight children over a two-year period. Paediatric
      replantation with its minute anatomy is technically very demanding. Joints should
      be reconstructed, epiphyses preserved and bone shortening kept as minimal as
      possible. Complications are not more than those in adults. All the replanted
      digits in our series survived. Seven of the ten replanted digits were normal in
      size. Six of the eight patients regained good to excellent functional use of the
      replanted digits. All but three of the joints at and distal to the level of
      injury regained active motion ranging from 10 degrees to 70 degrees with an
      average of 42 degrees. One had primary fusion of the distal interphalangeal joint
      of his amputated index finger. All the preserved epiphyses had remained open at
      the last follow-up. Replantation in children may be technically difficult but is
      very rewarding. We had a high success rate with good functional return and
      continuing growth.

PMID- 8572522
TI  - Postoperative continuous interscalene brachial plexus blockade for hand surgery.
AB  - Interscalene brachial plexus blockade is a well-established means of providing
      analgesia and anesthesia for upper extremity surgery. Extension into the
      postoperative period with continuous infusions of 0.25% bupivacaine provides
      several added advantages. Our survey over two years covered 126 patients
      undergoing surgery by the Department of Hand Surgery of our hospital.
      Postoperative verbal analogue pain scores obtained for three days showed scores
      of 4 or less (range 0 to 10) being reported by more than 70% of all patients with
      6.3% and 11.9% requiring additional narcotics and non-steroidal anti-inflammatory
      drugs, respectively. Compliance with early occupational therapy was good with
      only 7 patients having difficulty with active mobilisation as a result of
      excessive motor blockade. The insertion complication rate was 11.1%; all these
      cases were attributed to the bolus dose given and resolved over the next few
      hours. Eighteen (14.3%) of the patients developed complications while on
      continuous infusion, the most frequent being catheter dislodgement and pain at
      the insertion site. In all we found this method of providing postoperative
      analgesia to be effective, inexpensive and easy to implement in our large
      hospital setting.

PMID- 8572524
TI  - A preliminary report of tissue preservation with University of Wisconsin cold
      storage solution in major limb replantation.
AB  - We report our results using University of Wisconsin (UW) cold storage solution in
      two cases of major replantation of the upper extremity. We employed a technique
      of a complete vascular washout with 1000 ml UW solution at 4 degrees Celsius at
      120 cm hydrostatic pressure into the artery via a size 18 cannula. The ischaemic
      time of the amputated limbs were 7 hours and 11 1/4 hours respectively. No
      fasciotomy was performed upon revascularisation and minimal swelling was observed
      postoperatively. No post-ischaemic syndrome was encountered following the
      replantation surgery. With a follow-up of 10 and 16 months respectively, muscle
      and nerve viability were observed with sensory recovery and motor reinnervation.
      There was absence of muscle contracture and at subsequent surgical procedures,
      healthy musculature was present in the replanted limbs. These two clinical cases
      suggest that the UW solution has a role in extending the duration of tissue
      preservation and improving the quality of the tissues preserved.

PMID- 8572525
TI  - Intercostal nerve transfer to restore upper extremity functions after brachial
      plexus injury.
AB  - We report the efficacy of intercostal nerve transfer to restore elbow flexion,
      shoulder functions, and hand functions. One hundred and twelve patients with loss
      of elbow flexion were treated with intercostal nerve transfer to the
      musculocutaneous nerve and 97 (87%) of them regained grade 3 or 4 elbow flexion.
      Seven patients with loss of shoulder functions were treated with combined
      intercostal nerve transfer to the axillary nerve and phrenic nerve transfer to
      the suprascapular nerve, and 4 (57%) of them regained more than 80 degrees
      abduction and 5 (71%) regained more than 50 degrees external rotation starting
      with the forearm against the chest. To restore hand functions, intercostal nerves
      were sutured to the radial nerve or one of its branches in 40 patients and to the
      median nerve in 10 patients. Motor recovery was poor in both nerve transfers, but
      protective sensation was regained in the fingers innervated by the median nerve
      in 9 (90%) of the 10 patients. We conclude that intercostal nerve transfer after
      brachial plexus injury was a useful procedure to restore elbow flexion and
      shoulder functions, and for restoring a protective sensation in the fingers.

PMID- 8572526
TI  - Thumb reconstruction with a big toe microvascular wrap-around flap: a report of
      fifteen cases.
AB  - Fifteen thumb reconstructions were performed using the wrap-around procedure. A
      free wrap-around flap was taken from the big toe, and included the nail, and a
      part of the distal phalangeal skeleton. An iliac bone graft was added as the core
      of the reconstruction. One patient had an abnormal metatarsal arterial pattern
      which made the microsurgical reconstruction impossible, and another patient had
      early venous failure. Thirteen cases with successful thumb reconstruction were
      evaluated at an average of 27 months. Sensibility based on moving two-point
      discrimination ranged from 6 mm to 10 mm, and key pinch strength ranged from 0.5
      kg to 3 kg. None of the patients had the problem of bone graft resorption, cold
      intolerance or social unacceptance after surgery. A postoperative study of the
      feet by Harris mat revealed an area of increased pressure under the second
      metatarsal head and the big toe stump. None of the patients experienced
      difficulty when walking or running on level ground.

PMID- 8572527
TI  - Transfer of vessels in the management of thumb and ring avulsion injuries.
AB  - The main problem in avulsion or degloving injury is the extensive damage to long
      segments of vessels which makes direct suture of the structures difficult.
      Various techniques have been proposed over the years to bypass the segment of an
      injured vessel. Many of these are difficult and often require the execution of
      several vascular anastomoses. The transfer of vessels from adjacent fingers, as
      proposed by Doi, is a valid alternative. During the 5-year period from 1988 to
      1993, vessel transfer from adjacent fingers was carried out on 15 patients. Three
      patients suffered incomplete amputation and 5 patients suffered complete
      amputation of the thumb. In 5 cases these were severe crush injuries and in 3
      cases they were avulsion injuries. Seven patients suffered ring avulsion injuries
      of various degrees. The simplicity and reliability of the method (one case was
      unsuccessful) make this an important technique in the treatment of crush and
      avulsion injuries of the thumb as well as of ring avulsion injuries.

PMID- 8572528
TI  - Experimental models for microsurgical joint reconstruction in the upper
      extremity.
AB  - Microsurgical joint transplantation offers a new approach in the reconstruction
      of different joints. Experimental trials of the new innovations in the field of
      joint reconstruction are, however, necessary before they can become clinically
      useful. The purpose of this study was to investigate the possibility of using an
      autogenic second metatarsophalangeal joint transplant in the replacement of an
      acromioclavicular joint with the aid of skeletal and cadaver models. The factors
      influencing the stability, mobility and durability of the joint in the new task
      are discussed. Also, the features of operative techniques necessary in this kind
      of procedure are outlined with reference to microsurgical reconstruction
      possibilities. The major conclusion is that microsurgical joint transplantation
      can possibly be used in irreparable acromioclavicular joint situations and that
      the second metatarsophalangeal joint seems to be a versatile donor joint for
      different joint reconstruction problems of the upper extremity.

PMID- 8572529
TI  - Platelet-activating factor (PAF) receptor antagonism by WEB 2170 improves the
      survival of ischaemic skeletal muscle.
AB  - The platelet-activating factor (PAF) receptor antagonist, WEB 2170, significantly
      improved the survival of ischaemic rabbit skeletal muscle from 42% in saline
      infused muscle to 65% in WEB 2170-infused muscle at 24 hours post reperfusion.
      Evidence is presented which suggests that WEB 2170 inhibits neutrophil
      infiltration during reperfusion. In addition, tissue lipid peroxide levels and
      the release into blood of the enzyme creatine kinase were inhibited by local
      infusion of WEB 2170. In contrast, the level of oedema in muscles receiving an
      infusion of WEB 2170 was not different from that in saline controls. It is
      concluded that infusion of a PAF antagonist into ischaemic skeletal muscle at the
      time of reperfusion inhibits neutrophil recruitment and activation. These results
      provide an impetus for PAF receptor antagonism as a means of reducing reperfusion
      injury in limb replantation surgery.

PMID- 8572530
TI  - Digital replantations under local anaesthesia.
AB  - We performed 10 digital replantations under local anaesthesia. Nine were single
      digit replantations and one case had a digital replantation together with another
      digit revascularisation. Criteria for patient selection for the local anaesthetic
      procedure included healthy young individuals, solitary hand injury, ability to
      understand the procedure and a stable emotional makeup. A combination of 10 ml of
      lidocaine 1% and 10 ml of bupivacaine 0.5% was used for volar metacarpal block
      and a dorsal ring block to the base of the digit. The patient was simultaneously
      sedated with 10 mg diazepam intramuscularly. Standard intraoperative monitoring
      of blood pressure, continuous electrocardiogram and pulse oximeter were carried
      out. The average duration of surgery was 3 hours. There was complete pain relief
      intraoperatively and good postoperative sensory block for an additional 7 to 15
      hours. The technical execution of microsurgery was not compromised. All
      replantations were successful with no complication encountered from the use of
      local anaesthesia.

PMID- 8572531
TI  - The "stub" operation--modification of the Furnas and Vilkki technique in
      traumatic and congenital carpal hand reconstruction.
AB  - A technique is described for reconstruction of a pincer, by a second toe
      transfer, in traumatic and congenital deformities, leaving only the wrist. An
      anterior transfer on the radius allows the wrist mobility to compensate for the
      limited range of mobility of the second toe. Proximal situation of the toe gives
      the possibility of having plenty of tendons to balance the transfer. From 1987 to
      1992, 8 such operations were performed, 2 in traumatic amputations and 6 in cases
      of congenital anomalies. The mean age of the congenital patients was 13 months
      (range, 11 to 21 months) and the 2 traumatic patients were 17 and 20 years of
      age. In one of the traumatic cases, a sensibility of 11 mm was obtained at 22
      months and the wrist mobility in flexion was 55 degrees. The overall mobility of
      the toe was 35 degrees. In the second traumatic case, the two-point
      discrimination was 11 mm on the second toe and 10 mm on the great toe pulp. The
      wrist mobility remains limited (around 20 degrees) but distant contact is
      possible. In most of the congenital patients the mean mobility reached an average
      of 40 degrees at the toe level whereas the wrist mobility was an average of 52
      degrees, an improvement over peroperative values. In all the 8 patients, the
      epiphyses remain open.

PMID- 8572532
TI  - Distal radial fasciocutaneous flap.
AB  - A fasciocutaneous flap on the radial aspect of the distal forearm is an axial
      flap based on a branch of the distal part of the radial artery. The flap is
      reinforced by the fasciocutaneous arteries arising from the dorsal carpal rete.
      The vascular anatomy and the cutaneous territorial definition of the flap has
      been studied by cadaveric dissection of injected specimens using coloured latex
      and methylene blue solution. The flap measuring 5 x 7 cm with a pedicle length of
      2.5 cm can be harvested to resurface the skin defect on the palmar and dorsal
      surface of the wrist, carpometacarpal and base of the first metacarpal bone.

PMID- 8572533
TI  - Limb salvage surgery with microsurgical reconstruction for the treatment of
      musculoskeletal tumours involving the upper extremity.
AB  - Microsurgical reconstructive techniques have been applied in the management of 14
      patients with malignant bone and soft tissue tumours as well as for 30 patients
      with benign but aggressive bone lesions affecting the upper extremity.
      Vascularised bone grafts were used in 6 patients with malignant bone tumours and
      30 patients with aggressive bone lesions. Reconstruction with soft tissue free
      flap transfer was required in 6 patients with soft tissue defects, primarily
      following excision of soft tissue tumours in 2 and after excision of recurrent
      tumours in 4 patients. Microneural dissection and vascular reconstruction were
      performed in 2 patients with tumours around the major neurovascular bundles. The
      patients were followed up for varying periods, ranging from 1 to 12 years and
      assessment of the limb function was performed using Enneking's system of
      evaluation. There were no local recurrences. In the malignant tumour group, 3
      patients died of systemic disease, 7 were alive but with disease and 4 were
      disease free. Extremity function was excellent in 3 patients, good in 6 patients,
      fair in 4 patients and poor in 1 patient. In the benign bone tumour group,
      extremity function was graded as excellent in 12 patients, good in 14 patients,
      fair in 3 patients and poor in 1 patient. The vascular bone grafts united in all
      but 3 patients at 4 months following surgery. Minimal donor site complications
      had been recorded and there had been no failures. Useful limb salvage may thus be
      achieved with the application of microsurgical techniques for a variety of
      indications in limb salvage surgery after tumour excision.

PMID- 8572535
TI  - Tourniquet paralysis in microsurgery.
AB  - Tourniquet paralysis is a serious complication after surgery. The authors report
      15 cases recorded in their institution from 1972 to 1992. Seven were a
      consequence of routine operations on the upper limb and 8 were after
      microsurgical procedures. In the first group, the incidence of tourniquet
      paralysis was 1 in 7000 and this does not differ from published reports. In the
      second group, the incidence of complications is higher: 1 in 4300 cases. In all
      15 cases the Tinel sign was absent. Great care was taken to distinguish all the
      painful conditions which ranged from simple hyperalgesia to allodynia and
      causalgia. The distressing aspect of tourniquet paralysis is that all the main
      nerves of the upper limb (median, radial and ulnar), distally to the elbow, are
      usually affected by the paralysis. In the two groups, the three nerves were
      affected in 13 cases and the ulnar nerve was partially spared in 3 cases. In both
      groups the radial nerve was more severely affected. It took an average of 105
      days for complete recovery for the first group (range, 30-210 days) and 115 days
      for the second group (range, 20-180 days). Only in 1 patient in the first group
      was functional recovery incomplete. According to the authors' experience, general
      safety factors should be considered before using tourniquet. The tourniquet
      should be prohibited in patients with congenital susceptibility to nerve
      compression and should be used with caution in cases of underlying coagulation
      disorders and neuropathies, in tiny cachetic patients and in patients with
      systemic lupus erythematosus. In microvascular procedures its use should be
      limited to the first phase of replantation.

PMID- 8572534
TI  - Major limb replantation: a Thai experience.
AB  - From May 1986 to December 1992, we performed 36 major limb replantations in 35
      patients; 30 were complete and 6 were incomplete amputations. Twenty-eight of
      these patients were male. Their ages ranged from 5 to 81 years, the average being
      22 years. The levels of injury were 13 hemihand, 8 wrist, 5 lower forearm, 5
      upper forearm, and 5 above the elbow amputation. The degrees of injury were 8
      guillotine, 14 local crush, 9 diffuse crush, and 5 avulsion amputation. There
      were a partial loss of digits in 4 hemihand amputations and one failure in an
      above-elbow amputation--a limb survival rate of 95%. The functional result was
      evaluated in 30 patients, one with bilateral hemihand. Most patients regained
      useful hand function, with 20 achieving a grade I functional result--an ability
      to resume original work--or grade II functional result--an ability to do some
      gainful work--according to Chen's criteria. The best functional results were
      obtained in injuries which were near the wrist joint.

PMID- 8572536
TI  - Role of leukaemia inhibitory factor (LIF) in rat peripheral nerve regeneration.
AB  - The cytokine leukaemia inhibitory factor (LIF) favours the survival and growth of
      axons in vitro. The efficacy of this factor in the in vivo model has been the aim
      of this study. Following nerve transection and immediate entubulation repair in
      the rat sciatic nerve, this study demonstrated that (1) LIF promotes the growth
      of a population of axons of greater cross-sectional area after 6 and 12 weeks in
      comparison to either saline (negative control) or basic fibroblast growth factor
      (bFGF) (positive control), (2) LIF improves the nerve conduction velocity of
      regenerating axons, (3) LIF has a positive effect on skeletal muscle mass
      following nerve repair, (4) the benefits of LIF on skeletal muscle appear to be
      somewhat independent of reinnervation as similar observations are made where
      there is no growth of a tissue bridge within the tube, and (5) the effects of LIF
      seem to be potentiated by the addition of fibronectin.

PMID- 8572537
TI  - Dental problems in junctional epidermolysis bullosa: report of a case with
      treatment considerations.

PMID- 8572538
TI  - Controlling the production of dentists.
AB  - A review is presented of the successful effort to control the number of dentists.
      Future projections indicate that this reduction may have gone too far. The need
      for careful planning is emphasized.

PMID- 8572539
TI  - Central hemangioma. Review and a case report.
AB  - Central hemangioma is a rare vascular tumor of bone. When present in the head and
      neck region, it usually affects the vertebrae and skull: it very rarely affects
      the jaw bones. Its early detection and treatment are important as any minor
      trauma may result in fatal hemorrhage. A case of central hemangioma of the
      mandible is reported.

PMID- 8572540
TI  - Argyrophilic nucleolar organizer region associated proteins in human oral normal
      mucosa, verrucous carcinoma, and squamous cell carcinoma.
AB  - Silver-binding nucleolar-organizer regions (AgNORs) were counted in sections from
      formalin-fixed, paraffin-embedded blocks of 24 cases of well-differentiated
      squamous cell carcinoma, 6 cases of verrucous carcinoma, and 11 cases of normal
      oral mucosa. Two methods of AgNORs counting were used. The mean number of
      AgNORs/nucleus (mAgNORs) was used as indicator of the DNA content, and the
      percentage of cells containing five or more AgNORs/nucleus (pAgNORs) as indicator
      of the proliferative activity of the cells. These two methods were used to
      examine their possible contributory value as a diagnostic aid to distinguish
      between the types of carcinoma. The pooled mean counts were: normal oral mucosa
      mAgNORs 2.41 +/- 0.44 and pAgNORs 3.10 +/- 2.54 (mean +/- SD); verrucous
      carcinoma: mAgNORs 3.55 +/- 0.39 and pAgNORs 23 +/- 6.99; squamous cell
      carcinoma: mAgNORs 4.74 +/- 1.04 and pAgNORs 49.88 +/- 23.41. Although the
      differences of mAgNORs and pAgNORs counts were statistically significant, there
      was overlap of the counts between verrucous carcinoma and squamous cell
      carcinoma. These two methods of AgNORs counting cannot be used as a diagnostic
      aid to distinguish between these variants of squamous cell carcinoma.

PMID- 8572541
TI  - Immunoglobulins in the saliva of diabetic patients with periodontitis.
AB  - The study was conducted to estimate the concentration of immunoglobulins in the
      saliva of diabetic and nondiabetic patients with periodontitis. The salivary
      immunoglobulins G, A and M (IgG, IgA, IgM) were determined in 50 patients with
      type II or noninsulin dependent diabetes mellitus (NIDDM) and 50 non diabetic
      patients with periodontitis. The values were compared with that of 50 age and sex
      matched controls. IgG, IgA were found to be significantly increased in diabetic
      patients with periodontitis, compared to nondiabetic patients and controls.
      Though an increase in IgM was found in diabetic patients it was not significant.
      The altered immune response observed may be due to the response to a greater
      antigenic challenge which in turn may be responsible for the increased incidence
      of periodontitis in diabetic patients. Further studies in this field may help to
      establish this association.

PMID- 8572542
TI  - Van der Woude syndrome.

PMID- 8572543
TI  - Intraoral salivary duct carcinoma: a clinicopathological study of four cases and
      review of the literature.
AB  - Salivary duct carcinoma (SDC) is a distinctive entity of highly malignant
      salivary gland tumors. We present the clinical features and outcomes of four
      cases in minor salivary glands and of 69 additional cases previously reported in
      the literature. The tumor occurs most frequently in the sixth and seventh decades
      of life with a 3.8:1 male preponderance. The prognosis is dismal. Sixty-one
      percent of patients were dead within 5 months to 10 years (mean 25 months) and
      the rate of lymph node metastasis was 60%. Twenty-eight percent of patients were
      without evidence of the disease for 13 months to 9 years (mean 33 months). The
      histologic features, differential diagnosis, and origin of SDC are discussed.

PMID- 8572544
TI  - Dens evaginatus in a Chilean population.
AB  - A high rate of occurrence on dens evaginatus (DE) is reported in certain cultural
      groups in a Chilean population. Factors affecting the reported incidence of DE
      are discussed as are the clinical complications and treatment requirements
      related to this anomaly.

PMID- 8572545
TI  - Multiple odontogenic keratocysts: a case report.
AB  - Multiple odontogenic keratocysts are very rare, and when present are generally
      associated with one of the syndromes. In the present case a twelve-year-old
      female child presented with multiple odonotogenic keratocysts. Investigations did
      not show any other abnormalities suggestive of the presence of any syndrome.

PMID- 8572547
TI  - The comparison of vertical height and width of maxillary sinus by means of
      Waters' view radiograms taken from dentate and edentulous cases.
AB  - In the present study the vertical height and width of the maxillary sinus were
      measured by means of standardized Waters' view radiographs taken from 30 dentate
      and 30 edentulous subjects. All patients were healthy and were in the same age
      group of 35 to 40 years. Male and female ratios were equal in the groups.
      Measurements were compared between dentate and edentulous cases by means of T
      test. A significant difference was found in the height of the maxillary sinus (T
      = 8.21 p < 0.001) between dentate and edentulous cases with the maxillary sinus
      height increasing in edentulous cases. This may be due to the absence of teeth in
      the dead arch. No significant differences obtained in the width of the maxillary
      sinus between dentate and edentulous cases.

PMID- 8572546
TI  - Appearance of fracture caused by emphysema.
AB  - A case presenting radiographic appearance of a fracture line associated with
      emphysema which occurred in the removal of a mandibular third molar is reported.
      The cause of the fracture line in the radiograph is discussed together with the
      benefit of CT in diagnosis.

PMID- 8572548
TI  - Otocephaly.

PMID- 8572549
TI  - Intraoral spindle-cell lipoma: report of a case and literature review.
AB  - Spindle-cell lipoma (SCL) of the oral cavity is very rare. There are only four
      such reported cases in the literature. A concise literature review of SCL and a
      case report of a SCL affecting the cheek and lip of a 23-year-old man is
      presented.

PMID- 8572550
TI  - Russell-Silver syndrome: a study of 3 cases.
AB  - Russell-Silver syndrome, a syndrome of unknown etiology, is characterized by
      short stature of prenatal onset, triangular facies, asymmetry, variations in the
      pattern of sexual development, and other abnormalities, such as cafe-au-lait
      pigmentation, clinodactyly, and dental and oral abnormalities. We report three
      cases of Russell-Silver syndrome, all of which had dental anomalies. The clinical
      features of the syndrome are discussed.

PMID- 8572551
TI  - Induction of osteodentin and abortive enamel in adenomatoid odontogenic tumor.
AB  - Adenomatoid odontogenic tumor (AOT) with induction of calcified dentin with or
      without concomitant formation of enamel is exceedingly rare. This paper reports a
      case of AOT showing induction of osteodentin and abortive enamel. The patient was
      a 15-year-old male with a well-circumscribed intraosseous lesion containing the
      crown of the embedded left maxillary canine. Histologically, induction of
      osteodentin and abortive enamel was seen, in addition to characteristic
      histological features of AOT. The review of the English literature yields that
      the present case is the second AOT with induction of both dentin and enamel.

PMID- 8572552
TI  - A probable case of a cysticercosis presenting as an incidental intracranial
      calcification on a lateral cephalogram.
AB  - A 42-year-old female in whom intracranial calcifications were incidentally
      identified on a lateral cephalogram is presented. Follow-up CT scans and her
      social history led to the most probable diagnosis of cysticercosis, an
      infestation by larva of the tapeworm Taenia solium, of the brain. A differential
      diagnosis of intracranial calcifications on plain film skull views is presented.

PMID- 8572553
TI  - Tetracyclines and calcified tissues.
AB  - Tetracyclines are widely used in medical and dental practice. Since these drugs
      chelate calcium salts they are incorporated into bones and teeth during
      calcification. A review of the literature on the pharmacology of these drugs,
      their incorporation into calcified tissues and the management of tetracycline
      stained teeth is given.

PMID- 8572554
TI  - Pemphigus vulgaris: gingival involvement. A case report.
AB  - Pemphigus is an autoimmune disease in which intraepithelial vesicles and bullae
      of the skin and oral mucosa are produced by the action of autoantibodies against
      specific desmosomal proteins of squamous epithelium. Usually, oral lesions will
      appear before skin lesions, and in a majority of the cases only oral lesions are
      present. The dentist may then be the first to make and early diagnosis. The
      importance of this case report is to alert the dentist that subtle gingival
      lesions can be recognized and treated early in such a life-threatening disease.
      Diagnosis is based on the clinical presentation and confirmed by histologic study
      and direct immunofluorescence. This case describes the clinical signs, symptoms,
      histology, and immunofluorescence of pemphigus vulgaris of the gingiva.

PMID- 8572555
TI  - Proinsulin level in diabetes mellitus measured by a new immunochemiluminometric
      assay.
AB  - Proinsulin, the precursor of insulin and C-peptide, is detectable in the
      circulation and is a potential marker of beta-cell dysfunction. Currently,
      circulating proinsulin can be measured accurately without the interference of
      insulin or C-peptide by immunometric assays and a few specific radioimmunoassays.
      An immunochemiluminometric assay was developed in our laboratory by using two
      immunopurified polyclonal antibodies of C-peptide and insulin from two goats. The
      C-peptide antiserum was labeled with acridinium ester. The insulin antiserum was
      immobilized onto a plastic bead. With this assay, proinsulin levels found in
      noninsulin-treated patients with noninsulin-dependent diabetes mellitus (63 +/-
      58 pmol/L; n = 19) were significantly higher (p < 0.05) than levels in insulin
      treated patients with noninsulin-dependent diabetes mellitus (30 +/- 24 pmol/L; n
      = 43), and both were significantly higher (p < 0.001) than proinsulin levels in
      patients with insulin-dependent diabetes mellitus. In addition, there was a
      negative correlation between proinsulin levels and duration of years on insulin
      therapy in patients with noninsulin-dependent diabetes mellitus (r = -0.4795; p <
      0.01).

PMID- 8572556
TI  - Detection of cystic fibrosis delta F508 mutation by anti-double-stranded DNA
      antibody.
AB  - This study evaluated an enzyme immunoassay (EIA) as a screening tool for
      detection of the most common mutation (delta F508) in cystic fibrosis (CF).
      Guthrie card bloodspots were extracted to remove whole blood polymerase chain
      reaction (PCR) inhibitors. The washed filter paper was directly amplified under
      standard (98 bp amplicons) or modified PCR conditions (491 bp amplicons) for the
      delta F508 mutation. Monoclonal anti-double stranded deoxyribonucleic acid
      antibody was used to detect competent hybrid formation between PCR products and
      normal (N) and mutant (M) cDNA (deoxyribonucleic acid) probes coated to
      microtiter plate wells. Under standard conditions, mean relative color production
      (N/M) via an enzyme-linked horseradish peroxidase secondary antibody was 8.8, 0.6
      and 0.04 for individuals normal, heterozygous and homozygous for the CF delta
      F508 mutation, respectively (n = 27). Comparison of EIA results to those obtained
      by tris-borate-EDTA/8 percent polyacrylamide gel electrophoresis (TBE-PAGE)
      yielded excellent correlation (100 percent) for all three genotypes (n = 27). In
      comparison to TBE-PAGE, the EIA was 5 to 10 fold more sensitive when serially
      diluted PCR samples were evaluated. Larger PCR products (491 bp amplicons) for
      the CF delta F508 mutation obtained under modified conditions were not resolved
      by TBE-PAGE. The EIA, however, demonstrated equal sensitivity to the 98 bp and
      491 bp amplicons. Performance time for TBE-PAGE analysis was substantially
      shorter (25 percent) than the EIA (3.5 to 4 h and 4.5 to 5 h, respectively) when
      small batches of samples (n = 5) were analyzed. The TBE-PAGE was not, however,
      convenient for screening large numbers of PCR-amplified samples (n > 15).

PMID- 8572557
TI  - Damage to DNA by cadmium or nickel in the presence of ascorbate.
AB  - The interactive effects of the anti-oxidant ascorbate (Asc) and the metals
      cadmium (Cd, as CdCl2) or nickel (Ni, as NiCl2) on the in vitro formation of
      breaks in double-stranded deoxyribonucleic acid (d/s DNA) were determined.
      Concentrations of 50 microM Cd or 200 microM Ni were dosed for 4 hours in
      factorial combinations with 500 microM Asc in RPMI 1640 medium (7 percent bovine
      serum) in which AHH-1 TK+/- cells (a spontaneously transformed human B
      lymphoblastoid cell line by Gentest Corp.) were replicating. In combination with
      Asc, Cd caused significant d/s DNA breaks (p < 0.01, n = 5), while Cd in the
      absence of Asc produced only a slight (but not significantly different) amount of
      d/s DNA damage when compared to the cells with no Cd added. The Asc alone was not
      damaging. The Cd caused damage to the d/s DNA only when Asc was present. The
      percent of d/s DNA remaining following the respective treatments was: +Cd+Asc, 13
      +/- 3; +Cd-Asc, 46 +/- 8; -Cd+Asc, 54 +/- 5; -Cd-Asc, 55 +/- 7. Conversely, the
      presence of Ni resulted in increased amounts (percent) of d/s DNA compared to
      control values: +Ni+Asc, 63 +/- 5; +Ni-Asc, 58 +/- 5; -Ni+Asc, 52 +/- 1; -Ni-Asc,
      51 +/- 4, (p < 0.05, n = 3). The contrasting results between Cd and Ni in the
      presence of Asc may reside in the point of action; while Cd acts directly on DNA,
      Ni is reported to act on heterochromatin. Although Asc is a recognized anti
      oxidant, its presence in the media mixture potentiated d/s DNA damage from the
      Cd. This may be caused by a Fenton-type reaction in which an antioxidant in the
      presence of metal generates hydroxyl radicals and consequently d/s DNA breaks.
      Oxidative reactions between metals, oxygen, and antioxidants such as Asc may
      represent an important mechanism of cell death, toxicity, and transformation.

PMID- 8572558
TI  - Cross-sectional assessment of renal function in the inhabitants of a cadmium
      polluted area.
AB  - To understand the development of cadmium (Cd)-induced renal tubular dysfunction,
      cross-sectional assessment of renal function in the inhabitants of the Cd
      polluted Jinzu River basin in Toyama, Japan, was carried out. Sixty-seven men and
      78 women, aged 56 to 71 years whose urinary beta 2-microglobulin (beta 2-m)
      exceeded 1,000 micrograms/g creatinine, were examined and divided into five
      groups according to their values of fractional excretion of beta 2-m (FE beta 2
      m). Comparisons were made between six groups including the inhabitants of a non
      polluted area as a reference group. Significantly increased values of fractional
      excretion of urate (FEUA), calcium (FECa), sodium (FENa), and chloride (FECl),
      serum creatinine and beta 2-m, and urinary protein were detected even in the
      subjects with FE beta 2-m level below 1 percent compared with the reference
      group. Fractional phosphate reabsorption (percent TRP) was significantly
      decreased in the subjects with FE beta 2-m level above 10 percent. Creatinine
      clearance (CCr) decreased with increase in FE beta 2-m, and the subjects with FE
      beta 2-m above 30 percent showed significantly decreased CCr values compared to
      those with FE beta 2-m below 30 percent. In summary, FEUA, FECa, FENa, and FECl,
      as well as low-molecular-weight proteins such as beta 2-m, are increased in the
      early stage of Cd-induced renal tubular dysfunction. Although percent TRP was
      maintained by the decreased CCr, there was a marked decrease in percent TRP in
      subjects with progressive stage showing FE beta 2-m level above 10 percent. No
      sex difference in renal tubular dysfunction was found in this cross-sectional
      study.

PMID- 8572559
TI  - Single jejunoileal and right colonic carcinoids as midgut tumors. A study
      collating immunophenotypes and histogenesis.
AB  - The jejunoileum and the right colon, both of which are located in the midgut,
      have some histologic similarities such as the presence of Paneth cells and
      intraepithelial endocrine cells (IEECs). Since gastrointestinal (GI) carcinoids
      arise from the same stem cells as GI endocrine cells, the question was whether or
      not there might also be similarities in the histogenesis of jejunoileal
      carcinoids (JICs) and right colonic carcinoids (RCCs). Ten single JICs and 3 RCCs
      together with their respective controls were stained using various neurohormonal
      immunoreagents. Our results showed that neither the JICs nor the RCCs appeared to
      arise from a background of diffuse IEEC hyperplasia. Furthermore, in the
      jejunoileum, serotonergic progenitor cells appear to have a proclivity for
      neoplastic transformation, as do cells of the pancreatic polypeptide and glucagon
      lineage in the right colon.

PMID- 8572560
TI  - Clear nuclear changes in Hashimoto's thyroiditis. A clinicopathologic study of 12
      cases.
AB  - Histologic sections of thyroid glands resected from 12 patients with Hashimoto's
      thyroiditis have been studied in which areas were present showing clear nuclear
      changes such as those seen in papillary carcinoma. The patients' ages ranged from
      28 to 78 years (mean = 57.3); 11 were women and one was a man. The lesions
      presented as focal, ill-defined areas displaying clear nuclear changes of the
      cells within otherwise well-circumscribed adenomatous nodules, or as small
      clusters of cells showing the characteristic clear nuclear features randomly
      admixed with the Hashimoto's elements. Histologically, the lesions were
      characterized by a range of nuclear features that included optically clear
      nuclei, prominent cytoplasmic invaginations with intranuclear cytoplasmic
      inclusions, and occasional nuclear grooves. In two cases, focal papillary
      formations were seen that were lined by cells with optically clear nuclei. In two
      other cases, well-circumscribed nodules bearing the architectural features of
      trabecular hyalinizing adenoma with focal clear nuclear changes were also
      present. In three cases, small (< 0.5 cm) well-circumscribed nodules bearing
      cytological features indistinguishable from those of microscopic papillary
      carcinoma were also present in addition to the areas of clear nuclear change.
      Follow-up of 1.5 to 19 years (mean = 9 years) showed no evidence of recurrence or
      metastases in any of our patients. Our study appears to indicate that thyroid
      follicular epithelium in patients with Hashimoto's thyroiditis may exhibit a
      range of clear nuclear changes similar to those encountered in papillary
      carcinoma. Such changes may represent another form of response of follicular
      epithelium to the underlying autoimmune process with possible premalignant
      connotation. However, they should be interpreted in context with the rest of the
      findings within the involved gland to avoid an overdiagnosis of malignancy.

PMID- 8572561
TI  - [The pseudo-tumoral form of hepatic tuberculosis. Five case reports].
AB  - The authors report 5 cases of pseudotumoral tuberculosis of the liver. They
      essentially involved young men from disadvantaged socio-economic backgrounds.
      Clinically, poor general condition with massive weight loss was constant, while
      pyrexia and hepatomegaly were sometimes absent. Hepatobiliary ultrasonography
      revealed hypoechogenic or even anechogenic lesions between 1.5 and 3.5 cm in
      diameter. Diagnostic confirmation was histological after needle biopsy. The
      outcome after antibiotic treatment with or without drainage, was recovery, with
      ultrasonographic normalization of the liver, in all patients, with a mean follow
      up of 22 months.

PMID- 8572562
TI  - [Diagnostic efficiency of histological and simple microbiological tests for
      Helicobacter pylori detection in a community hospital].
AB  - The objective of this study was to compare histology and microbiology (direct
      method, urease test, culture) for the detection of Helicobacter pylori in antral
      biopsies. Thirty-six patients, aged between 18 and 82, with a peptic ulcer
      (active or not), or gastritis or duodenitis were studied. Eighteen patients (50%)
      had a positive culture, 17 (47%) had a positive urease test, 16 (41%) had
      positive direct microbiology and 15 (42%) had positive histology. Correlation
      between histology and culture was 84%. This study confirms the good sensitivity
      of histology and the urease test for the detection of Helicobacter pylori.
      Combination of both methods could optimise detection of the organism.

PMID- 8572563
TI  - [Colloid cancer of the anus: value of anal ultrasonography and nuclear magnetic
      resonance imaging].

PMID- 8572564
TI  - [Physiopathology and surgical treatment of hepatic encephalopathy after porto
      caval anastomosis].
AB  - Surgical porto-caval anastomosis and percutaneous intrahepatic porto-caval shunt
      are effective in the management of bleeding esophageal varices but are associated
      with liver failure and a high incidence of encephalopathy. The neurochemical
      consequences of ammonia detoxification may be important with regard to the
      development of hepatic encephalopathy. Maintenance of splanchnic venous
      hypertension leads to less post-shunt hepatic encephalopathy because of
      diminished absorption of ammonia. Results of medical treatment of hepatic
      encephalopathy are contradictory. However, mortality and controversial results of
      surgical treatment in hepatic encephalopathy restrict its indications to a small
      number of patients. Prevention of hepatic encephalopathy begins with the
      selection of patients for surgical or percutaneous shunting.

PMID- 8572565
TI  - [Unusual locations of hydatid cysts].
AB  - The most common sites of hydatid disease (HD) are represented by the liver and
      the lungs. In 10% of cases, HD arises in unusual viscera: mainly spleen (0.9 to
      8%) and also kidney, bones, heart, brain, peritoneum (0.5 to 5%). Other
      exceptional location was described in less than 1% of all cases of hydatid cysts.
      Ultrasonography and CTscan are highly suggestive of HD, while serologic tests are
      variable. The cysto-pericystectomy is the gold standard procedure but sometimes
      unsuitable for particular sites. In that cases a conservative approach (partial
      pericystectomy) is mandatory to preserve the organ function. The place of
      adjuvant medical treatment remains questionable.

PMID- 8572566
TI  - [Prevention of hepatitis A and hepatitis B by vaccination].
AB  - In spite of low endemic levels in France, hepatitis A and hepatitis B remain
      major concerns for public health. Seroprevalence of antibodies against hepatitis
      A (anti-HAV), declining below 15% in the 20 years-aged subjects, highlights an
      increasing susceptibility to hepatitis A. Later in the life, HAV infections
      become more serious and expansive. Control measures against hepatitis B have
      nearly stopped HBV spread linked to blood transfusions and mothers to infants
      transmission. Now, common risk factors are first sexual exposure, then injecting
      drug use, especially among young people. Vaccination is recognized as the most
      effective process for prevention. Recombinant hepatitis B vaccines have taken the
      place of plasma-derived vaccines. Although non responder individuals and escape
      mutants of HBV may hamper vaccinal coverage, hepatitis vaccines are highly
      immunogenic in immunocompetent people, allowing simplified schedules and reduced
      HBsAg dosages for children. Inactivated HAV vaccines now licensed prove to be
      highly immunogenic after only one injection. Hepatitis B vaccination targeted on
      high risk groups remains imperative but inadequate for reducing hepatitis B
      occurrence. A universal hepatitis B vaccination program in childhood and early
      adolescence would nearly stop the spread of HBV in the populations before ten
      years. Likewise, hepatitis A vaccination of travelers to endemic areas, all
      individuals exposed to contaminations from fecal sources, and food handlers,
      could reduce the spread of HAV in the community but would not completely prevent
      outbreaks of hepatitis A. Advantages of universal immunization of babies are not
      proved yet. Implementation of preventive strategies first needs a comprehensive
      surveillance of viral hepatitis in France.

PMID- 8572567
TI  - [Perioperative artificial nutrition programmed for the adult surgical patient.
      Saint-Mande, December 16, 1994: The Francophone Society of Enteral and Parenteral
      Nutrition and the French Society of Anesthesia and Resuscitation].

PMID- 8572568
TI  - Apoptosis mediates the selective toxicity of caffeic acid phenethyl ester (CAPE)
      toward oncogene-transformed rat embryo fibroblast cells.
AB  - The active component of the folk medicine propolis, caffeic acid phenethyl ester
      (CAPE), displays selective toxicity toward cloned rat embryo fibroblast (CREF)
      cells transformed by a spectrum of diverse acting oncogenes. Identification of
      the mode of action of CAPE should provide useful information for possible
      applications of this compound for cancer therapy. The present study uses a series
      of oncogene transformed, oncogene-reverted and CAPE-resistant oncogene
      transformed CREF cells to investigate the mechanism underlying the increased
      sensitivity of transformed cells to CAPE. A direct relationship exists between
      the cytotoxic effects of CAPE and the induction of DNA fragmentation and
      apoptosis. DNA degradation into nucleosomal fragments and apoptotic shifts in DNA
      cell cycle profiles occur in CAPE-treated CREF cells transformed by wild-type 5
      adenovirus (Ad5), a mutant Ad5 (H5hr1), the wild-type Ad5 E1A transforming gene,
      v-src, Ha-ras and the human papilloma virus type 18 transforming genes (HPV-18).
      In contrast, untransformed CREF cells, human fibroblast expression library
      induced morphological revertants of Ad5- and v-src-transformed CREF cells, and
      Krev-1 expressing revertant Ha-ras-transformed CREF cells are resistant to CAPE
      induced toxicity and apoptosis. Similarly, mutant Ad5-transformed CREF cells
      selected by step-wise growth in increasing concentrations of CAPE are resistant
      to growth inhibition and apoptosis induced by CAPE. These findings indicate that
      expression of the transformed phenotype by rodent cells evokes sensitivity to
      CAPE induced toxicity through apoptosis. The acquisition of CAPE sensitivity in
      rodent cells is independent of the mode of action of the oncogenic agent. CAPE
      may prove useful as an antiproliferative agent in cancer cells transformed by
      mechanistically diverse acting oncogenes.

PMID- 8572569
TI  - Contrasting patterns of selenium excretion by female CD rats treated with
      chemically related chemopreventive organic selenocyanate compounds.
AB  - We previously demonstrated that while both benzyl selenocyanate (BSC) and 1,4
      phenylenebis(methylene)selenocyanate (p-XSC) have high efficacy as cancer
      chemopreventive agents in several animal tumor models, p-XSC is less toxic. Using
      atomic absorption spectrophotometry, we compared the urinary and fecal excretion
      of total selenium derived from p-XSC and BSC in female CD rats. The results
      indicate that there exist distinct differences in the selenium excretion patterns
      when these compounds are administered orally, but not when they are administered
      i.p. In terms of the percent dose, the total selenium excreted in the 5 days
      following equimolar dosing (50 mumol/kg) of p-XSC or BSC, respectively, was as
      follows: after gavage, 68% or 3% in the feces and 6% or 18% in the urine; after
      i.p. administration, 9% or 4% in feces and 16% or 20% in urine. These results
      indicate that while most of the BSC administered orally is absorbed in the
      gastrointestinal tract, most of the p-XSC given the same way is not absorbed.
      This difference would account for the significantly lower tissue levels of
      selenium derived from orally administered p-XSC compared to BSC, and accounts, in
      part, for the lower oral toxicity of p-XSC compared to BSC. Subsequent studies
      employing o- and m-XSC, isomers of p-XSC, demonstrate that the excretion patterns
      of selenium are significantly different, depending on the position of
      substitution. In vitro studies suggest that the differences among BSC and the
      three XSC isomers with regard to absorption is probably due to different extent
      of binding to components of the gut contents. The results of these studies are
      useful for the future design of less toxic and more effective chemopreventive
      organic seleno-cyanates.

PMID- 8572570
TI  - A DNA motif present in alpha V integrin promoter exhibits dual binding preference
      to distinct transcription factors.
AB  - Antisense inhibition of the RelA subunit but not the NFKB1 subunit of NK-kappa B
      transcription factor results in a block of cellular adhesion and inhibition of
      tumor cell growth in vitro and in vivo. Studies aimed at dissecting the molecular
      mechanism of antisense relA action led to our identification of a kappa B-like
      motif present in aV integrin promoter. The alpha V/kappa B motif is closely
      related to RelA/c-Rel-binding sequences, such as 65-2 and TF-1. However, unlike
      these two kappa Blike motifs, the alpha V/kappa B motif detected a nuclear Sp1
      activity distinct from kappa B activity, which was subsequently confirmed to be
      derived from Sp1. In comparison to the conventional GC box-containing Sp1 motif,
      the alpha V/kappa B motif also binds in vitro to c-Rel and RelA but not to NFKB1.
      Antisense inhibition of RelA inhibited the alpha V/kappa B activity. Direct in
      vivo competition of alpha V/kappa B-binding activity by a decoy approach also
      resulted in inhibition of alpha V/kappa B activity in intact cells. A variant of
      the alpha V/kappa B motif was found to retain the dual ability to detect Sp1 and
      the NF-kappa B complex in the nuclear and cytoplasmic extracts. Such dual
      interacting ability of a DNA motif offers yet another way of gene regulation in
      vivo and hence can affect cellular growth. Our results identify alpha V integrin
      as one of the molecular targets for relA/NF-kappa B and may explain growth
      inhibition by antisense relA.

PMID- 8572571
TI  - Establishment of an experimental model for continuous intraportal infusion of
      chemo/immunotherapeutic agents in the rat.
AB  - The results of adjuvant continuous intraportal chemotherapy in preventing hepatic
      metastasis, following curative colorectal surgery, are still equivocal. To
      improve the efficacy of this treatment we tried to establish an experimental
      model for continuous intraportal infusion in Wistar male rats. Using a drug
      infusion balloon catheter, which can be fixed on the back of the rat, the
      continuous intraportal administration of chemo/immunotherapeutic agents was
      carried out in 47 rats for 5 days. Of them, 23 received chemotherapeutic
      (Mitomycin C/5-fluorouracil) and 24 received chemoimmunotherapeutic (Mitomycin
      C/5-fluorouracil/Lentinan) agents. The overall success rate of complete 5-day
      infusion of the agents was 70.2%. The concentration of 5-fluorouracil in the
      peripheral blood ranged from 5ng/ml to 17ng/ml (mean 10.4ng/ml) and in the portal
      blood from 192ng/ml to 610ng/ml (mean 312.0ng/ml) following the perfect
      continuous infusion of the agents. It can thus be suggested that our established
      experimental model can be used for the study of continuous intraportal infusion
      in unrestrained rats.

PMID- 8572572
TI  - Development of human leukemia U-937 cell sublines resistant to doxorubicin:
      induction of differentiation and altered sensitivities to topoisomerase-directed
      drugs.
AB  - Cell sublines resistant to doxorubicin (DOX) were developed from the human
      leukemia cell line, U-937/WT, exposed to stepwise DOX increases. In contrast to U
      937/WT cells, the DOX-resistant U-937/RD cells have longer doubling time; are
      more differentiated along the monocytic lineage as determined by the presence of
      morphological features and mRNA coding for the monocyte colony-stimulating factor
      1 receptor; synthesize the apoptosis-associated Bax protein; are less sensitive
      to apoptosis-inducing topoisomerase II-directed drugs, apparently because of
      increased synthesis of P-glycoprotein; and are practically non-tumorigenic when
      xenografted in nude mice. However, U-937/WT and U-937/RD cells exhibit similar
      sensitivity to the apoptosis-inducing drug 9-nitrocamptothecin. These findings
      suggest that several mechanisms are involved in the development of DOX-resistance
      in U-937 cells, and further, 9-nitrocamptothecin can overcome resistance to DOX.
      These findings may have clinical implications.

PMID- 8572573
TI  - Lysozyme stimulates lymphocyte response to ConA and IL-2 and potentiates 5
      fluorouracil action on advanced carcinomas.
AB  - The oral administration of 100 mg/Kg/day of hen egg-white lysozyme (Lysozyme) for
      8 consecutive days to mice bearing advanced MCa mammary carcinomas and treated
      with 5-fluorouracil (5-FU) increases the efficacy of 5-FU on primary tumor growth
      and on lung metastasis formation and particularly on the postsurgical survival
      time. These effects are accompanied by the correction of the reduced in vitro
      response to ConA of lymphocytes obtained from the spleen of the treated mice. In
      vitro, lysozyme is capable of inducing proliferative activity in a population of
      blast cells, obtained by a mixed population of mononuclear cells harvested from
      the spleen of healthy mice, and of evoking a marked proliferative effect to IL-2
      in a condition in which, in lysozyme untreated lymphocytes, IL-2 is completely
      uneffective. These data stress the effects of lysozyme on host immunity following
      oral administration and moreover indicate the beneficial role of this peptide in
      conditions in which the increase of host responses can significantly contribute
      to the success of the treatment.

PMID- 8572574
TI  - Possible function of CEA as cell-contact inhibitory molecule.
AB  - Ever since it was discovered that CEA, as member of the CEA-gene family, is part
      also of the Ig-supergene family, to which molecules involved in cell interactions
      like cell adhesion or cell recognition belong, great efforts were made to prove
      that CEA is also an adhesion molecule. At present this seems to be an accepted
      fact. In the present study we advance a different theory which is based on the
      expression pattern of CEA during ontogeny and in malignancy and which is
      suggestive of CEA functioning more as a signal protein prohibiting further
      cell/cell contact rather than as an adhesion molecule. In the malignant state the
      expression of this molecule on the surface of tumor cells would facilitate
      migration and motility, i.e., metastases formation. Furthermore it would prevent
      a tight contact between cytotoxic effector cells and CEA expressing target cells.

PMID- 8572575
TI  - Two in situ labeling techniques reveal different patterns of DNA fragmentation
      during spontaneous apoptosis in vivo and induced apoptosis in vitro.
AB  - BACKGROUND: Two new enzymatic reactions were described recently to detect
      apoptotic cell death in situ viz in situ end labeling (ISEL) and terminal
      deoxynucleotidyl transferase mediated UTP nick end labeling (TUNEL) of fragmented
      DNA. A comparative study was conducted to detect in vivo and in vitro apoptotic
      death using these two techniques. Experimental design; Spontaneous apoptous cell
      death was detected in plastic embedded tumor biopsies from patients with non
      Hodgkin's lymphoma (NHL), head and neck squamous cell carcinomas (HNSCC), and
      breast cancer using these two in situ methods. Uninvolved normal tissues adjacent
      to breast tumors and a lymph node metastasis of breast tumor were also studied.
      Furthermore, apoptotic death induced by different doses of etoposide (VP16) was
      also studied in HL60 cells by in situ methods and by agarose gel electrophoresis.
      RESULTS: Interestingly, whereas NH1 and HNSCC biopsies showed comparable levels
      of detectability with the two techniques, the breast tissues be it neoplastic,
      normal or metastatic, revealed apoptosis detectable only by TUNEL and not by
      ISEL. Similarly in HL60 cells, the percentage of apoptotic cells or apoptotic
      index (AI) determined by TUNEL was significantly higher than that determined by
      ISEL. A double labelling of these HL60 cells for ISEL and TUNEL also revealed a
      higher proportion of cells labeled positively for TUNEL as compared to those
      labeled for ISEL. Agarose gel electrophoresis revealed characteristic DNA
      laddering only at 35 microM dose of VP 16. No smearing of DNA was found in any
      group ruling out the necrotic death. In vivo, in one HNSCC specimen apoptosis and
      necrosis could be differentiated by the difference in staining intensity. Both
      methods stained necrotic chromatin fragments very lightly. The DNA fragments
      generated during apoptosis could be of unique lengths (ie 180-200 bp or
      multiples) but have differently staggered ends. These fragments may be 3'
      recessed, 5' recessed or blunt ended. While TUNEL can label all three types, ISEL
      labels only those with 3' recessed ends. CONCLUSIONS: Thus our data show that the
      DNA fragments formed during spontaneous apoptosis in breast tissues and
      preferentially during VP16 induced apoptosis in HL60 cells are either 5' recessed
      or blunt ended, being distinctly different from 3' recessed fragments seen in NHL
      and HNSCC or with a lesser frequency in VP 16 treated HL60 cells. Specific
      fragmentation patterns could be a result of activation of different endonucleases
      which as indicated by our data could be tissue specific and may be differentially
      activated by different chemotherapeutic agents. Therefore, screening for the
      presence of specific endonucleases in different tissues and for agents
      specifically activating them would have major clinical implications.

PMID- 8572576
TI  - Progesterone and beta-estradiol influence the cell density-dependent distribution
      of cyclic nucleotides across the cell membrane of human C4-I cells (squamous
      carcinoma of the uterine cervix) by a non-genomic mechanism.
AB  - The ratio between extracellular levels of cGMP and cAMP (cGMPex/cAMPex) has been
      proposed as diagnostic tool in many forms of malignancies. In vitro and in vivo
      studies have shown that sex steroids effect extracellular levels of cyclic
      nucleotides. Cyclic changes of these hormones in premenopausal women may disturb
      the interpretation of the diagnostic marker. C4-I cells grew in the presence of
      beta-estradiol and progesterone in a chemically defined medium. Cells were
      sampled during the logarithmic growth phase. Cyclic nucleotide levels were
      determined by RIA. Receptor status was evaluated by immunocytochemistry.
      Progesterone increased the cGMPex/cAMPex at all cell densities tested. This
      effect resulted from increased cGMP and reduced cAMP extrusion. Estradiol had no
      clear effect on cGMPex/cAMPex even when inhibition of cAMP extrusion was observed
      at low cell density. Receptors for steroids were not detectable. Sex steroids
      interact with cyclic nucleotides in C4-I cells in a non-genomic manner.

PMID- 8572577
TI  - Sensitivity of anticancer drugs in NIH3T3' cells transfected with oncogenes
      accompanied by pSV2neo vector.
AB  - NIH3T3 cells and NIH3T3 cell lines, which were transfected with several oncogenes
      accompanied by pSV2neo vector, were observed for their survival rate when treated
      with commonly used anticancer drugs. The survival rates in the cell line
      transfected with the pSV2neo vector only did not differ significantly from that
      of parental NIH3T3 cells against bleomycin, nimustine and adriamycin, but it was
      significantly more resistant to cisplatin and more sensitive to mitomycin C.
      Therefore, the survival rate in each transfectant was compared with that in the
      pSV2neo transfectant. The Val-12, v-Ha-ras, v-int-2, v-erbB or v-abl
      transfectants accompanied by pSV2neo vector were significantly more sensitive to
      cisplatin than transfection with pSV2neo vector only. The Val-12, v-Ha-ras, v-int
      2 and v-abl transfectants were significantly more sensitive, and the v-erbB
      transfectant more resistant to bleomycin than the pSV2neo transfectant. The v-int
      2, v-erbB, frg, v-raf and v-myc transfectants were more sensitive, and the v-Ha
      ras transfectant more resistant to nimustine than the pSV2neo transfectant. The N
      ras, v-Ha-ras, v-sis, v-int, v-abl and v-myc transfectants were significantly
      more sensitive to adriamycin than the pSV2neo transfectant. The v-sis and v-int-2
      transfectants were more sensitive, and the c-Ki-ras, Val-12, v-erbB and the v-src
      transfectants more resistant to mitomycin C than the pSV2neo transfectant. Thus
      there was no relationship between the drug sensitivity and the location of
      oncogenes, but the transfection was associated with either increased or decreased
      sensitivity to a number of commonly used anticancer drugs. Therefore, it may be
      important to take into consideration or overexpression of oncogenes in cancer
      chemotherapy.

PMID- 8572578
TI  - Prognostic relevance of Ki-67 antigen and c-myc oncoprotein in malignant fibrous
      histocytoma.
AB  - 47 cases of malignant fibrous histiocytoma were stained immunohistochemically for
      the presence of Ki-67 antigen and c-myc oncoprotein. Percentage of Ki-67 and c
      myc positive cells correlated with each other and with grade of tumour, mitotic
      index, cellularity and survival time of patients, but not with the extent of
      necrosis. Differences of mean values of Ki-67 index between grade I and grade II
      tumours as well as between grade II and grade III tumours were highly
      statistically significant. All 3 parameters connected with c-myc expression
      (index, intensity and score) differed significantly between grade I and grade II
      tumours but not between grade II and grade III MFH. The possible differential
      role of Ki-67 antigen and c-myc oncoprotein for improvement of grading is
      discussed.

PMID- 8572579
TI  - Effect on cell survival and protein synthesis of benzylidene-glucose (BG) and the
      deuterated analogue P-1013 in cultured cells.
AB  - 4,6-Benzylidene-D-glucose (BG), is a known antitumour substance with low clinical
      toxicity. In order to increase the antitumour activity of BG a deuterated
      compound, 4,6-benzylidene-D-d1-glucose, denoted P-1013, was synthesised. P-1013
      induced significantly greater cell inactivation than BG in mammalian cells of 10
      different cell lines, implying that the deuteration of BG leads to increased
      cellular effects. Testing loss of colony forming ability following a 24 h
      exposure, the IC50 values, i.e. inhibitory doses that reduced the number of
      surviving treated cells by one half, were found to range from 3.2 to 10.8 mM BG
      and from 1.3 to 7.7 mM P-1013. In addition, P-1013 induced significantly greater
      inhibition of protein synthesis than BG in several of the tested cell lines. No
      cross-resistance to P-1013 or BG was seen in the MDR-positive colchicine
      resistant KB-CHR-8-5 cell line compared with its parental cell line KB-3-1. Thus,
      the deuterated benzaldehyde derivative P-1013 is a reversible protein synthesis
      inhibitor inducing greater cellular effects than its undeuterated analogue BG in
      cultured mammalian cells.

PMID- 8572580
TI  - Expression of asparagine synthetase mRNA through asparagine independent signal
      transduction pathway that might involve protein kinase C in BALB3T3 cells.
AB  - Basal level of asparagine synthetase mRNA in BALB3T3 cells was elevated when the
      cells were shifted from medium containing a high concentration (3.3 mM) of
      asparagine to one lacking asparagine. We then studied whether the expression of
      asparagine synthetase mRNA is also mediated through other asparagine-independent
      signaling pathways. BALB3T3 cells grown to near confluence were quiesced by serum
      starvation, and various agents were then added to the culture to examine the
      enzyme activity and mRNA level of asparagine synthetase. 12-O
      tetradecanoylphorbol-13-acetate (TPA), a direct activator of protein kinase C
      (PKC), elevated dose and time dependently the level of asparagine synthetase mRNA
      even in Eagle's minimum essential medium with alpha modification (MEM alpha) that
      contains protein-constituting 20 amino acids and is supplemented with 3.3 mM
      asparagine. Staurosporine and H-7, PKC inhibitors, strongly blocked the fetal
      bovine serum-dependent accumulation of asparagine synthetase mRNA. TPA could also
      enhance the activity of asparagine synthetase within 24 h at concentrations of
      more than 10 nM. These results suggest that expression of asparagine synthetase
      gene can be induced both through a pathway that involves PKC and through a
      pathway the origin of which is a reduced concentration of asparagine in BALB3T3
      cells.

PMID- 8572582
TI  - Anti-proliferative and cytokinetic effects of tumor necrosis factor-alpha,
      interferon-alpha and 5-fluorouracil on a human tumor xenograft.
AB  - We have previously reported that interferon-alpha (IFN-alpha) and tumor necrosis
      factor-alpha (TNF-alpha) blocked the cell cycle progression of cancer cells at
      the S to G2 transition, causing a synergistic antitumor effect. In this study,
      the combined effects of both these cytokines and 5-fluorouracil (FUra) on tumor
      growth and cell cycle progression were investigated in a human colon cancer cell
      line, RPMI 4788, transplanted in CD-1 nude mice. Daily administration of IFN
      alpha and TNF-alpha for 21 days markedly suppressed the tumor growth and induced
      cytokinetic alterations in which S phase cells were increased and cells in G2/M
      phase were decreased. FUra added to these cytokines further suppressed tumor
      development but did not affect the cytokinetics further. Combination of FUra and
      cytokines in a low dose, either of which alone had no effect, suppressed the
      tumor growth. These findings demonstrate that IFN-alpha, TNF-alpha and FUra have
      a distinct antitumor effect in combination.

PMID- 8572581
TI  - Immunological analysis of inhibition of lung metastases by fucoidan (GIV-A)
      prepared from brown seaweed Sargassum thunbergii.
AB  - The antimetastatic effect of GIV-A (fucoidan) and/or 5-FU was examined in an
      experimental model of lung metastases induced by Lewis lung carcinoma in mice.
      Injection of GIV-A i.p. after removal of the implanted primary tumor inhibited
      the development of lung metastases. Combination treatment with GIV-A and 5-FU
      inhibited significantly the lung metastases. The number of peritoneal
      macrophages, total cells and macrophages in the lung increased in mice treated
      with GIV-A. Binding of the third component of complement (C3) cleavage products
      (C3b) to the C3 receptor on peritoneal macrophages after i.v. injection of GIV-A
      was enhanced, as shown by the fluorescent antibody technique. Lung metastases
      were inhibited by i.v. injection of peritoneal macrophages activated with GIV-A.
      GIV-A depressed aniline hydroxylase and aminopyrine demethylase activities of the
      hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover, the
      concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood) was
      increased significantly by coadministration of GIV-A. The picryl chloride-induced
      delayed type hypersensitivity (PC-DTH) response in mice was depressed after the
      implantation of tumor and treatment with 5-FU. GIV-A restored the suppression of
      PC-DTH by 5-FU, but did not increase the PC-DTH of normal mice. GIV-A not only
      enhanced the degree of spleen cell-mediated sheep red blood cell (SRBC) hemolysis
      (quantitative hemolysis of SRBC), the indexes of the spleen and thymus and the
      number of spleen cells, but also restored the suppressive effect of 5-FU. In the
      group receiving GIV-A, the percentages of splenic Thy1.2-, L3T4- and asialo GM1
      positive cells were significantly increased as compared with the tumor-bearing
      mice treated with saline. Furthermore, the L3T4+/Lyt2+ ratio showed a tendency to
      increase, and the Lyt2+/Thy1.2+ ratio was decreased. These results suggest that
      the antitumor effect of GIV-A may be correlated with the changing pattern of the
      Thy1.2-, L3T4- and asialo GM1-positive cells, C3 activation, macrophage
      activation and depression of the hepatic microsomal drug-metabolizing system.
      These findings raise the possibility that GIV-A may have clinical value in the
      prevention of cancer metastasis.

PMID- 8572583
TI  - Chemoprevention of diethylnitrosamine-induced liver foci and hepatocellular
      adenomas in C3H mice.
AB  - The ability of six proposed chemopreventive agents to prevent diethylnitrosamine
      induced liver foci and tumors in male C3H mice was investigated. The test agents
      were administered by intraperitoneal injection on days 13, 14 and 15 of age and
      starting at 21 days of age continuously in the diet until sacrifice at 161 days
      of age. The mice were administered 4.0 mg/kg diethylnitrosamine by
      intraperitoneal injection on day 15 of age and two hours after the test agent.
      Diethylnitrosamine-induced 62.4 +/- 4.2 foci of altered hepatocytes and 22.1 +/-
      2.1 hepatocellular adenomas, which were reduced by diallyl sulfide to 21.6 +/-
      2.4 and 6.73 +/- 1.13 and phenethyl isothiocyanate to 28.2 +/- 3.4 and 5.06 +/-
      1.53 foci and adenomas, respectively. Difluoromethylornithine and ellagic acid
      only decreased the yield of adenomas without affecting the yield of foci of
      altered hepatocytes and of total lesions. N-Acetyl-l-cysteine and 1,2
      oxothiazolidine-4-carboxylate did not affect the yield of either liver lesion.
      When administered starting prior to diethylnitrosamine-initiation and continuing
      until sacrifice, diallyl sulfide and phenethyl isothiocyanate demonstrated
      chemoprevention of tumorigenesis.

PMID- 8572584
TI  - Phospholipases A2 in ras-transfected fibroblasts.
AB  - Phospholipase A2 (PLA2) generated lipid biomediators can facilitate neoplastic
      progression. Specific PLA2 alterations associated with ras oncogene expression
      were determined by comparison of PLA2 activities in nontumorigenic rat embryo
      fibroblasts (CREF cells) and their tumorigenic ras oncogene-transfected
      counterparts (CREF-T24 cells). The high molecular mass cytosolic PLA2 activity is
      2-3 fold higher in CREF-T24 cells as compared to CREF cells. Western blotting
      analyses indicate increases in the level of this enzyme and the proportion which
      migrates with phosphorylated enzyme in CREF-T24 cells. A PLA2 activity, with the
      characteristics of a group II PLA2, is readily detectible in particulate
      fractions from CREF-T24 cells following ammonium sulfate extraction/cation ion
      exchange chromatography. In contrast, this activity is minimal in similarly
      prepared CREF cell samples. While the CREF-T24 cells have increases in two PLA2
      activities associated with the release of arachidonic acid, the CREF-T24 and CREF
      cells are similar with respect to Ca2+ independent, particulate fraction
      associated PLA2 activities.

PMID- 8572585
TI  - Hemin toxicity in a human epithelioid sarcoma cell line.
AB  - The major cytotoxic component of hemin was identified as metal free
      protoporphyrin IX in an epithelioid sarcoma cell line (VA-ES-BJ) and a
      glioblastoma cell line (U-373 MG) by exposing the cell lines to the iron chelator
      deferoxamine, tin-protoporphyrin IX, and protoporphyrin IX. The contribution of
      lipid peroxidation and free radical generation to toxicity was examined using DL
      buthionine-[S,R]-sulfoximine (BSO), and 21-aminosteroid (lazaroid, U74500A).
      Hemin caused significantly greater toxicity in VA-ES-BJ than in U-373 MG. While
      exogenous PpIX was more toxic than hemin in both cell lines, this toxicity was
      not due to iron depletion following intracellular heme formation since ferric
      citrate did not reverse PpIX toxicity. Pre-treatment with BSO enhanced hemin
      toxicity in the VA-ES-BJ cell line but not in U-373 MG, suggesting different
      modes of toxicity in the two cell lines. Exposure to lazaroid protected only VA
      ES-BJ from protoporphyrin-induced toxicity implicating a specific sensitivity to
      lipid peroxidation and/or free radical generation by this cell line. These
      characteristics of the VA-ES-BJ cell line distinguish it from the glioblastoma
      and emphasize its utility for exploring cytotoxic effects of hemin and its
      precursors.

PMID- 8572586
TI  - Structure-activity relationship of coumarins in xanthine oxidase inhibition.
AB  - Esculetin(4), umbelliferone(7-hydroxycoumarin)(3) and 7-hydroxy-4-methyl
      coumarin(8) are strong xanthine oxidase inhibitors (IC50 = 20.91, 43.65 and 96.70
      microM respectively). Based on this observation, the structure of 7-hydroxy
      coumarin(3) plays a very important role in xanthine oxidase (XO) inhibition. The
      6-hydroxy group present in the molecule of 7-hydroxy coumarin, e.g. esculetin(4)
      enhanced the activity, whereas substitution by the 6-methoxy group, e.g.
      scopoletin (5), reduced the inhibitory effect. Furthermore, 6-glycoside group
      present in the molecule of 7-hydroxy coumarin, e.g. esculin (6,7-dihydroxy
      coumarin 6-glucoside)(12) strongly decreased the inhibitory effect as well as
      scoparone(6), the fully methylated derivative of esculetin (4). In contrast to 7
      hydroxy coumarin(3), however, 4-hydroxy coumarin(13) showed only a weak effect on
      XO inhibition. 4-Substituent present in the molecule of 7-hydroxycoumarin also
      reduced the activity but the degree of reduction depended on the substituents: 7
      hydroxy-4-methylcoumarin (8) < 7-hydroxycoumarin-4-acetic acid (7) < 7-hydroxy-4
      trifluoromethylcoumarin (9). Their percent inhibition at 100 microM was 62.47,
      38.46 and 26.84% respectively. 8-substituent present in the molecule of 7-hydroxy
      coumarin (3), such as 7,8-dihydroxy-6-methoxycoumarin(10) and fraxin(7-hydroxy-6
      methoxycoumarin 8-glucoside)(11) reduced the activity as compared with scopoletin
      (5). Their percent inhibition at 100 microM was 18.4 and 6.9% respectively, which
      indicated that the more bulky the 8-substituted in the structure, the weaker the
      inhibitory activity on XO. 3,4,8-Trimethyl-7-hydroxycoumarin(14) which
      substitution by the methyl at 3,4 & 8 in the structure of 7-hydroxycoumarin(3)
      also reduced the activity as compared with 7-hydroxycoumarin(3). It seems that
      the double bond in the structure of coumarin(1) played an important role in the
      activity as compared with coumarin(dihydrocoumarin)(2). The apparent inhibition
      constants(Ki) of esculetin(4), umbelliferone (3) and 7-hydroxy-4
      methylcoumarin(8) were 2.056, 21.683 and 4.86 microM respectively and induced
      competitive, uncompetitive and a mixed type of inhibition of the enzyme with
      respect to the substrate xanthine.

PMID- 8572587
TI  - Enhancing potency of neopterin toward B-16 melanoma cell damage induced by UV-A
      irradiation and its possible application for skin tumor treatment.
AB  - The enhancing potency of the oxidized form of neopterin (NP) towards long
      wavelength ultraviolet light (UV-A) induced cytotoxicity was examined in vitro
      using mouse melanoma (B-16) cells. A sufficient dose of UV-A irradiation was used
      to cause damage (measured in terms of reduced DNA synthesis) to about 30% of the
      irradiated cells. NP drastically enhanced the UV-A-induced cell damage, whereas
      the reduced form of neopterin (NPH4), which possesses a strong antioxidative
      activity, abolished the UV-A-induced cell damage in a dose-dependent manner.
      These data suggest that radical oxygen species (ROS) may be involved in UV
      Ainduced B-16 cell damage. Among various radical scavengers examined, only
      catalase protected B-16 cells from UV-A-induced cell damage and also abolished
      the enhancing potency of NP, suggesting that hydrogen peroxide may mediate the
      cell damage. We obtained similar results in another experiment on B-16 cell
      damage induced by hydrogen peroxide instead of UV-A. In an in vitro analysis of
      the chemilumi-nescence induced by hydrogen peroxide, NP remarkedly enhanced the
      signal intensity at a high concentration, while NPH4 reduced the intensity in a
      dose-dependent manner. These results suggest that elevation of the hydrogen
      peroxide-mediated cytotoxicity by NP may be involved in its enhancing potency
      toward UVA-induced B-16 cell damage, and may also indicate the possible utility
      of the oxidized form of neopterin as an enhancer for UV-A-irradiation treatment
      of tumors.

PMID- 8572588
TI  - Effect of acute treadmill exercise on LFA-1 antigen expression in murine
      splenocytes.
AB  - The LFA-1 intercellular adhesion molecule (ICAM), expressed on human and murine
      CD8+ and natural killer (NK) cells, participates in cytolytic interaction with
      target cells. This study was designed to determine whether acute exercise alters
      the activity of CD11a (LFA-1) on NK cells. Fourty male C3H/HeNHSD mice were
      sacrificed before (sedentary) or at various time points after acute treadmill
      exercise (30 m/min, 4 degrees slope, 30 minutes). Splenic natural killer cell
      activity (NKCA) was determined using a standard 51Cr release assay, using fresh
      splenocytes or splenocytes which had been incubated for 3 days with 100 U rIL-2.
      10 micrograms/ml of mAb to LFA-1(anti-CD11a) or an equal volume of culture medium
      were added to the effector:target suspensions prior to 4.5 h incubation. There
      was a significant main effect of antibody treatment on cytolysis of tumour
      targets by fresh and IL-2 augmented splenocytes (p < 0.001); for both fresh and
      IL-2 augmented splenocytes, addition of anti-CD11a antibody reduced cytolysis of
      tumour target cells. Further, there was a significant main effect of exercise on
      fresh (p < 0.01) but not IL-2 augmented splenocytes cytolysis; this effect was
      due to differences in cytolytic activity between 30 and 120 minutes post
      exercise. Calculation of delta% in cytotoxicity showed that the capacity of mAb
      to CD11a to inhibit cytolysis was the lowest at 30 minutes after exercise (25%).
      The delta% in cytotoxicity was less pronounced in samples obtained from IL-2
      augmented splenocytes, irrespective of timing of exercise. These results suggest
      that acute exercise renders mouse splenocytes more resistant to the blockade
      effect of anti--CD11a (LFA-1) and, as result, may alter killing of tumour target
      cells in vitro.

PMID- 8572589
TI  - Captopril inhibits glioma cell invasion in vitro: involvement of matrix
      metalloproteinases.
AB  - We investigated the effects of captopril on the activity of matrix
      metalloproteinases (MMPs) secreted by T98G glioma cells and their invasiveness in
      vitro. On gelatin zymography, captopril inhibited gelatinolytic activities in the
      culture media of T98G cells. This inhibitory effect was reversed by the presence
      of excess zinc. In an in vitro invasion assay, invasion into the reconstituted
      basement membrane (Matrigel) by T98G glioma cells was inhibited by captopril in a
      dose-dependent manner. This inhibitory effect was also reversed by the addition
      of zinc to the culture media. However, at the effective concentration of
      captopril for the prevention of tumor cell invasion it did not inhibit the
      motility, adhesion to Matrigel or proliferation of T98G cells. These findings
      suggest that captopril inhibits the invasiveness of T98G glioma cells due to its
      MMP inhibitory activity, chelating zinc ions at the active center of MMPs.

PMID- 8572590
TI  - Effect of cepharanthin and hyperthermia on the intracellular accumulation of
      adriamycin in the NIH3T3 cell lines transfected with oncogenes accompanied with
      pSV2neo vector.
AB  - The influence of several oncogenes on drug resistance has recently been show by
      transfection studies. Therefore, we investigated the influence of transfection on
      adriamycin (ADR) in cell line transfected with several oncogenes accompanied with
      pSV2neo vector. There were differences in both the intracellular accumulation of
      ADR and its sensitivity among the transfectants used in this study. There was a
      good correlation with the intracellular accumulation of ADR and its sensitivity
      (r = 0.76, P = 0.002). Further, there were no differences in the ADR efflux among
      the ras-family transfectants. Therefore, the changes in ADR sensitivity may be
      due to changes in ADR influx. On the other hand, the ADR accumulation showed an
      increase of 1.14-1.29 fold by the treatment of 10 micrograms/ml CEP. Moreover,
      the ADR accumulation showed an increase of 1.29-3.11 fold by hyperthermia at 42
      degrees C. There was no significant difference in the ADR accumulation at 42
      degrees C among the transfectants, suggesting that the influence on the ADR
      accumulation may be counteracted by hypethermia at 42 degrees C.

PMID- 8572591
TI  - Bcl-2 expression in neuroblastoma is differentially regulated by differentiation
      inducers.
AB  - Neuroblastoma is characterized by differentiation in vivo and in vitro, and the
      process is known to be associated with changes in various gene expressions, among
      which is the bcl-2 gene whose major function may be potentially involved in the
      resistance to anticancer chemotherapy. We investigated the changing patterns of
      bcl-2 expression in neuroblastoma cell lines according to differentiation to
      assess whether the expression patterns can be differentially modulated by
      different types of differentiation inducers. Differentiation was induced in two
      neuroblastoma cell lines [SK-N-SH, SK-N-BE(2)] using all-trans-retinoic acid,
      gamma-interferon and EHS laminin, respectively. The levels of expression of bcl-2
      were analysed before and after differentiation using immunoblotting and
      subsequent densitometry. The expression patterns of bcl-2 differed according to
      the type of differentiation inducers. Its expression increased when treated with
      retinoic acid and EHS laminin along with neuronal differentiation, while
      differentiation with gamma-interferon treatment was associated with decreased bcl
      2 expression. Decreased expression of bcl-2 despite neuronal differentiation
      induced by gamma-interferon was thought to be important in that a certain
      differentiation pathway without increased drug resistance-related factor
      expression exists, which in turn has implications for the clinical application of
      gamma-interferon, combined with chemotherapy.

PMID- 8572592
TI  - Cytotoxicity of paclitaxel in comparison with other anticancer agents against
      neoplastic cells obtained from clinical gastrointestinal carcinoma tissue.
AB  - We examined the activity of paclitaxel against primary cultured cells from
      gastrointestinal neoplasmas, such as stomach, colon, hepatocellular and
      pancreatic cancer, and estimated the clinical use of paclitaxel. Antitumor
      activity, expressed as reduction in cell survival rates mediated by anticancer
      agents, was measured using [3H]thymidine incorporation into primary cell
      cultured. Percent survival rates for stomach, colon and hepatocellular cancer
      cells in the presence of 0.5 microM paclitaxel were 68.1%, 58.4% and 65.1%,
      respectively. Proportions of gastrointestinal cancer cases having percent
      survival rates of < or = 70% for paclitaxel, CDDP, MMC and ADM were 48.3%, 17.4%,
      28.0% and 21.1%, respectively. The rate for paclitaxel was the highest of all.
      The proportion of stomach, colon, liver and pancreatic cancer cases having a
      percent survival rate of < or = 70% in the percentage of paclitaxel were 55.6%,
      66.7%, 50.0% and 20.0%, respectively. In particular, the proportions of stomach
      and colonal cases having survival rates of < or = 70% for paclitaxel in spite of
      having survival rates of > 70% for other anticancer drugs were 75% (3/4) and 50%
      (2/4), respectively. From these results, it is probable that paclitaxel will
      demonstrate clinical activity in gastrointestinal tract cancers, such as stomach,
      colon, hepatocellular and pancreatic cancer.

PMID- 8572593
TI  - Maintenance of human hyperplastic prostate implants at different sites in athymic
      mice.
AB  - The present study determined the influence of implantation sites, androgens, and
      the graft's fibrovascular elements on the maintenance of epithelial elements of
      human benign hyperplastic prostate tissue (BPH) in the nude mouse. BPH fragments
      prepared from fresh surgical specimens were implanted subcutaneously (s.c.),
      intraperitoneally (i.p.), or under the renal capsules (r.c.) into male Beige nude
      mice, which had been implanted s.c. with a Silastic tube filled with 4
      dihydrotestosterone (DHT) or cholesterol. Two weeks later the BPH tissues were
      removed from the mouse and examined microscopically. The implants from all three
      sites maintained a comparable morphology, with epithelial and/or angio
      leiomyomatous stromal hyperplastic appearance, without striking signs of atrophy,
      irrespective of supplementation with DHT. Expression of proliferating cell
      nuclear antigen in the implants was comparable, indicating that there was no
      significant influence of implantation site on the proliferative ability of either
      epithelia or the stromal fibroblasts. The PCNA-positive cells in the implants,
      including the vascular and myofibrous elements, hybridized in situ to a human
      specific repeated-sequence DNA probe, indicating that these proliferating cells
      were of human origin. Our data suggest that during the early phases of the
      adaptation and maintenance of BPH implants, survival of epithelial cells is
      actively supported by fibro-vascular mesenchymal elements of the prostate grafts
      in a manner apparently unaffected by DHT supplements.

PMID- 8572594
TI  - Effects of two benzo[a]phenothiazines on multi-drug resistance (mdr) and tumor
      antigen expression.
AB  - Two benzo[a]phenothiazines 5H-benzo[a]phenothiazin-5-one (1), and its derivative
      6-methyl-5H-benzo[a]phenothiazin-5-one (2) inhibited the proliferation of human
      and mouse tumor cell lines. The multi-drug resistant (mdr) subline was more
      sensitive than its parent cell line to 5H-benzo[a]phenothiazin-5-one (1), 6
      methyl-5H-benzo[a]phenothiazin-5-one (2) was equally antiproliferative against
      the three cell lines tested. Rhodamine 123 efflux of mdr cells was more
      efficiently inhibited by 5H-benzo[a]phenothiazin-5-one (1) than by 6-methyl-5H
      benzo[a]phenothiazin-5-one (2). The exposure of adenovirus infected cells to 5H
      benzo[a]phenothiazin-5-one (1) resulted in a reduction of tumor-antigen
      expression, whereas 6-methyl-5H-benzo[a]phenothiazin-5-one (2) enhanced the T
      antigen expression.

PMID- 8572595
TI  - Effects of C18 fatty acid isomers on DNA synthesis in hepatoma and breast cancer
      cells.
AB  - The influence of geometrical isomerism on the growth regulatory effects of 18
      carbon unsaturated fatty acids on the incorporation of [3H]thymidine into DNA was
      studied in 7800NJ rat hepatoma and T47D human breast cancer cells. 9 cis, 12 cis
      linoleic acid was more inhibitory than the trans 9, trans 12 isomer (linolelaidic
      acid). The monounsaturated cis isomer, oleic acid, was also more inhibitory than
      the trans isomer. In contrast to published studies on the proliferation of breast
      cancer cells, we observed conditions in which linoleic acid was more inhibitory
      than conjugated linoleic acid for thymidine incorporation into DNA. Increasing
      the concentration of bovine serum albumin from 1 mg/ml to a physiological
      concentration of 38 mg/ml greatly diminished inhibitory effects and favored
      stimulatory effects on hepatoma and breast cancer cells. The results suggested
      that the growth inhibitory and stimulatory effects of C18 unsaturated fatty acids
      on cancer cells are influenced by geometrical isomerism and the ratio of the
      albumin to fatty acid concentrations.

PMID- 8572596
TI  - Human HT-29 colon carcinoma cells: mucin production and tumorigenicity in
      relation to growth phases.
AB  - The main aim of this study was to determine whether changes in mucin
      production/secretion during the growth phases of a human adenocarcinoma cell
      line, HT-29, are associated with a different tumorigenic potential. HT-29 cells
      cultured in DMEM supplemented with 10% FCS were harvested in the exponential and
      post-confluent phases of growth. Metabolic labeling of the cells was performed
      using [3H]-glucosamine. Following a 24 hr-incubation period, radioactivity was
      measured in 1 ml-aliquots of cell cytosol and culture medium. Concurrently, mucin
      synthesis was assessed by size exclusion chromatography of [3H]-glucosamine
      labeled glycoprotein in a Sepharose CL-4B column. Clonigenic assay in soft agar
      of pre- and post-confluent HT-29 cells was determined by scoring viable colonies
      according to size and number using phase-contrast microscopy. To assess in vivo
      tumorigenicity, pre-and post-confluent HT-29 cells (4 x 10(6)) in 0.2 ml DMEM
      were inoculated into nude mice. Tumor size and volume were recorded for 31 days.
      H-29 cells grew as multilayers of unpolarized, undifferentiated cells. Colony
      forming efficiency was similar at all growth stages. A significant increase in
      mucin synthesis was noted in HT-29 cells harvested in the exponential phase of
      growth compared to the stationary phase (148.3 +/- 41.9 versus 49.1 +/- 5.0, mean
      +/- SE, dpm/4 x 10(3) cells, p < 0.05). Mucin secretion was not significantly
      changed. Tumorigenicity in nude mice was consistently higher when the cells were
      injected in the exponential phase of growth. On day 31 after cell inoculation the
      average tumor volume/site was 332.7 mm3 in mice injected with HT-29 cells in log
      phase compared to 142.7 mm3 (p < 0.01) in animals which received post-confluent
      cells. Tumor weights were 0.36 g and 0.22 g respectively (p < 0.05). The present
      results indicate a definitive correlation between growth phases of HT-29 cells
      and mucin synthesis: mucin production was significantly higher in exponentially
      growing cells. The cloning efficiency in soft agar, a marker of in vitro
      tumorigenicity, was similar in HT-29 cells irrespective of the growth stage. A
      main finding of the present study was the increased in vivo tumorigenicity of
      colon cancer cells inoculated into athymic mice in the log phase of growth
      compared to cells harvested at post-confluence. These results are consistent with
      the view that mucin plays an important contributory role in determining
      tumorigenicity.

PMID- 8572597
TI  - Luteinizing hormone releasing hormone, estrogen, and progesterone receptors in
      canine mammary lesions and tumor cell lines.
AB  - Nineteen canine mammary lesions were analyzed for estrogen receptor (ER),
      progesterone receptor (PR) and luteinizing hormone releasing hormone receptor
      (LHRHR) content. In addition, nine previously established canine mammary tumor
      cell lines with known ER and PR were analyzed for LHRHR. The incidence of
      receptors in the mammary tumor lesions was 21% for LHRHR, 10% for ER and 30% for
      PR. Statistical correlation was not observed between receptor status and
      diagnosis of malignant, benign, or hyperplastic lesions. A relationship between
      LHRHR and ER and PR content of canine mammary lesions or cell lines was not
      evident. The presence of functional hormone receptors offers opportunity for
      hormonal treatment of mammary cancer which may not be completely treatable by
      surgery. The observation of LHRHR in canine mammary tumors may offer therapeutic
      interventions other than surgery for mammary tumors unresponsive to
      antiestrogens.

PMID- 8572598
TI  - In vitro and in vivo evaluation of o-carboranylalanine as a potential boron
      delivery agent for neutron capture therapy.
AB  - o-Carboranylalanine (B10H10C2CH2CHNH2COOH) is a carborane-containing amino acid,
      which has been synthesized as a potential capture agent for boron neutron capture
      therapy (BNCT) of cancer. The purpose of the present study was to develop a
      rational approach for the in vitro and in vivo evaluation of boron containing
      compounds that possibly might be used for BNCT. The in vitro uptake of
      carboranylalanine (CBA) was evaluated using two cell lines, the human melanoma
      MRA 27, and the murine Harding-Passey melanoma. Uptake of CBA by MRA 27 cells
      ranged from 135-551 micrograms B/10(9) cells following 3 hrs incubation with
      medium containing 100-113 micrograms B/ml and was not reduced by exposing the
      tumor cells to either rotenone, an inhibitor of electron transport, or by
      culturing them at ambient temperature (approximately 22 degrees C). Cellular
      uptake and elution of CBA occurred rapidly under in vitro conditions. Uptake of
      CBA was slightly greater than that of boronophenylalanine (BPA). Following a 3 hr
      incubation with CBA at a concentration of 106 micrograms B/ml, cell boron content
      was 255 micrograms B/10(9) MRA 27 cells, compared to 192 micrograms B/10(9) cells
      when cells were incubated with BPA at a concentration of 95 micrograms B/ml. In
      vivo studies initially were carried out using the Harding-Passey melanoma, which
      had been implanted intramuscularly (i.m.) into the right flank of BALB/c mice.
      Tumors were allowed to grow for 14 days at which time mice were injected
      intraperitoneally (i.p.) with either CBA or BPA (1.25 mgB/mouse), and were killed
      3, 6 and 8 hrs later. CBA attained a low tumor to blood ratio(1.0-1.4), and the
      tumor boron levels ranged from 15.7-26.2 micrograms B/g at 3 hrs and 3.3-19.9
      micrograms B/g at 6 hrs. Higher blood and lower tumor boron levels were observed
      at all time points with CBA compared to BPA, suggesting that CBA was not taken up
      selectively by the melanoma. Similar studies, carried out in rats bearing intra
      cerebral gliomas, failed to reveal detectable amounts of boron in the tumor. From
      the present study, it can be concluded that CBA does not appear to possess the
      requisite properties to be useful as a boron delivery agent for BNCT.

PMID- 8572599
TI  - Evaluation of in vitro cytotoxicity of carboranyl amino acids, their chemical
      precursors and nido carboranyl amino acids for boron neutron capture therapy.
AB  - The purpose of the present study was to define the in vitro cellular toxicity of
      three carborane-containing amino acids: p-(o-carboran-yl)-phenylalanine (CBPA), O
      (o-carboran-1-ylmethyl)-tyrosine (CBT), and o-carboranylalanine (CBA), which are
      analogues of phenylalanine, tyrosine, and alanine respectively. In addition, two
      of their chemical precursors: CBACN (B10H11C2-CH2CHNH2CN) and CBTCN (B10H11C2
      CH2OC6H4CH2CHNH2CN) and nido CBA were evaluated for their toxicity on human MRA
      27 melanoma cells. Hydroxypropyl-beta-cyclodextrin (beta-CD) initially was used
      to solubilize all the compounds except nido CBA in the toxicity assays Cells were
      incubated with the test compounds at varying concentrations for 24 hrs, following
      which the proliferative activity of surviving cells was determined by pulsing
      with tritiated thymidine ([3H]-TdR) for an additional 18 hrs. CBT at a
      concentration of 280 micrograms/ml was non-toxic when solubilized with beta-CD.
      CBA at a concentration of 350 micrograms/ml was non-toxic when solubilized with
      beta-CD, but when solubilized with DMSO produced a 50% reduction in uptake of
      [3H]-TdR at a concentration of 75 micrograms/ml. CBPA, solubilized with beta-CD,
      was nontoxic at a concentration of 400 micrograms/ml, while CBTCN and CBACN at
      concentrations of 50 micrograms/ml and 40 micrograms/ml, respectively, were both
      toxic, even when solubilized with beta-CD. Nido CBA at a concentration of 400
      micrograms/ml in medium was non-toxic. Although the toxicity of these boron
      compounds precludes their use as capture agents for Neutron Capture Therapy, they
      may have some potential for cytoreductive chemotherapy of cancer, and further
      evaluation may be warranted.

PMID- 8572600
TI  - A rapid method for the screening and typing of high risk HPVs using molecular
      biology techniques.
AB  - To date over 60 different human papilloma virus (HPV) types have been described
      and novel HPV genomes are still being identified. The identification and taxonomy
      of papilloma viruses has become increasingly complex However, some types,
      especially HPV-16, -18 and to a lesser extent HPV-31 and -33, which are found in
      a high proportion of invasive cervical cancers and their metastases, are
      classified as high risk types For preventive reasons it is important to identify
      and classify the different HPV types in clinical specimens. Many of the methods
      used until recently are cumbersome. In this paper we use molecular biology
      techniques which permit a rapid screening and typing of high risk HPVs in
      clinical specimens. The screening procedure is based on the very sensitive method
      of polymerase chain reaction. Using a set of general primers derived from the E1
      open reading frame, which anneal to a large variety of human papilloma virus DNA,
      we can classify samples into positive or negative for the presence of HPV
      sequences in a single step. The typing of the high risk HPV types is achieved by
      restriction enzyme analysis using the endonuclease Alu I which cleaves each high
      risk HPV type at different sites, thus permitting the easy identification of each
      type after agarose gel electrophoresis.

PMID- 8572601
TI  - Overexpression of NDP kinase nm23 associated with ploidy image analysis in
      colorectal cancer.
AB  - The nm23 gene was originally identified by differential hybridization between two
      murine melanoma cell sublines with low and high metastatic potential. Nm23 is
      localized on chromosome 17q21.3-22. Allelic deletions of chromosome 17 have been
      related to the progression of colorectal carcinomas. We have evaluated and
      compared the expression of nm23 NPD kinase protein using an immunohistochemical
      method and DNA ploidy evaluation with image analysis. This study was performed on
      20 patients, who underwent surgery for colorectal carcinoma. Patients were
      followed up during the period from 1992 to 1994. Results have shown an
      association between the parameters obtained for the nm23 NPD kinase protein
      expression, and aneuploid DNA and neoplastic progression. The expression of
      nucleoside diphosphate (NDP) kinase mm23 has been reported to be inversely
      related to the metastatic potential of experimental cells in human breast cancer.
      A relationship between the positivity in protein expression of gene product in
      the allele nm23 H1 and the state of the lymph nodes has also been found.

PMID- 8572602
TI  - Genetics of gastric cancer.
AB  - Although the death rate from gastric carcinoma in the US and other western
      communities has decreased in recent times, a similar trend has not been noted in
      other countries, especially S.E. Asia. Upto 95% of all malignant gastric
      neoplasms are adenocarcinomata, but other types of gastric cancer have evoked
      considerable interest in the literature. Genetic factors have been suspected of
      playing a pivotal role in the etiology of gastric cancer but no clear inheritance
      pattern has emerged and environmental influences remain the focus of many current
      theories of pathogenesis. Current evidence implicates the non-random involvement
      of certain chromosomes and related oncogenes especially Ras and p53. Genes that
      may predispose to gastric cancer have not been clearly implicated but some
      studies indicate a familial aggregation of gastric cancer. The objective of this
      review is to reappraise the role of genetics in the etiology of gastric cancer
      with special reference to relevant information for practicing clinicians.

PMID- 8572603
TI  - SOD2 (MnSOD) does not suppress tumorigenicity or metastasis of human melanoma
      C8161 cells.
AB  - Manganese superoxide dismutase (MnSOD, encoded by the SOD2 gene mapping to
      chromosome 6q25) has been implicated as a tumor suppressor and as a metastasis
      suppressor in some tumor cell lines. We showed that introduction of an intact
      chromosome 6 into the metastatic melanoma cell line C8161 completely suppressed
      metastasis but did not affect tumorigenicity (Welch et al., (1994) Oncogene
      9:255). The purpose of this study was to test whether SOD2 is the gene
      responsible for metastasis suppression. MnSOD protein levels of C8161 (measured
      by Western blot), before and after transfer of chromosome 6, showed no
      correlation with metastatic potential. To determine whether the lack of
      correlation was due to mutant, nonfunctional SOD2, a highly metastatic subclone
      of C8161 (C8161c1.9) was transfected with functional SOD2 or vector control
      (pSFFV). Metastatic potential and tumorigenicity were unchanged. Southern and
      Northern blots confirmed the presence of the transfected SOD2; however, total
      MnSOD protein and antioxidant activity were not significantly altered. These
      results suggest that levels of MnSOD are highly regulated within C8161 melanoma
      cells and that SOD2 does not suppress tumor formation nor metastatic potential in
      all human melanomas.

PMID- 8572604
TI  - TPK inhibitors differentially affect IFN-gamma activities.
AB  - The effect of various tyrosine protein kinase inhibitors on processes involved in
      the antiproliferative effect of interferon-gamma on WISH cells was studied.
      Following 24 hr treatment interferon-gamma inhibited thymidine incorporation into
      DNA and thymidine kinase activity, but no significant effect on cell number was
      observed. The isoflavonoid, genistein, which is a specific inhibitor of tyrosine
      protein kinase, reversed the inhibition in thymidine incorporation caused by the
      cytokine in a dose dependent manner. Prunetin, a member of the same group, did
      not significantly antagonize this effect. N alpha-tosyl-L-lysyl-chloromethane, a
      serine protease inhibitor which also serves as a tyrosine protein kinase
      inhibitor, partially reversed the effect of interferon-gamma at a concentration
      of 100 microM. The bioflavonoid, quercetin, a non-specific tyrosine protein
      kinase inhibitor, at a concentration of 30 microM completely abolished the action
      of interferon-gamma on thymidine incorporation. Genistein completely reversed the
      inhibition of thymidine kinase exerted by interferon, while quercetin had only a
      slight effect. However, the drugs could not antagonize the antiproliferative
      effect of interferon following 48 hr incubation, as measured by reduction of cell
      number. The results indicate that tyrosine protein kinase may play a role in the
      effects of interferon on thymidine metabolism and thymidine kinase activity. The
      differential effects of the inhibitors on thymidine metabolism and cell
      proliferation could support dissociation between the effect of interferon-gamma
      on these processes. Alternatively, this dissociation of effects could point to
      the limited use of inhibitors in clarifying modes of action as described.

PMID- 8572605
TI  - Adverse effects at adjuvant treatment of liver metastases in rat with RSU-1069 +
      microspheres, or liposomal MTP-PE.
AB  - Rats were inoculated via the portal vein with a suspension of tumor cells from a
      transplantable dimethylhydrazine-induced adenocarcinoma of rat colon. In one set
      of experiments, the bioreductive drug RSU-1069 was injected once via the portal
      vein with or without degradable starch microspheres (DSM) 10 mins after tumour
      cell inoculation. In another set the immunostimulator liposomal-encapsulated
      muramyl tripeptide phosphatidyl-ethanolamine (MTP-PE) was injected via the portal
      vein or penile vein 1 day before tumour-cell inoculation and then twice a week.
      The experiments were finished after 2 to 3 weeks. Tumour take, numbers and
      volumes were measured. RESULTS: RSU-1069 enhanced tumour growth when combined
      with DSM. Liposomal MTP-PE also increased tumour growth. CONCLUSION: A
      bioreductive drug combined with microspheres, known to suppress the growth of an
      established tumour, may enhance its growth in the adjuvant setting. An accepted
      immunostimulator may enhance tumour take. Drugs used for the treatment of tumours
      must be carefully employed, if applied in an adjuvant setting. The effect on the
      normal immune system should be further studied.

PMID- 8572606
TI  - Aminopeptidase inhibitor ubenimex (bestatin) inhibits the growth of human
      choriocarcinoma in nude mice through its direct cytostatic activity.
AB  - Ubenimex (bestatin), a potent inhibitor of aminopeptidases, is known to have
      immunomodulatory and host-mediated antitumor activities. In this paper, we
      investigated the inhibitory effects of bestatin on the growth of human
      choriocarcinoma both in vitro and in vivo using the established choriocarcinoma
      cell line NaUCC-4. Bestatin inhibited the in vitro proliferation of NaUCC-4 cells
      concentration- and time-dependently at more than 72 h incubation. DNA histograms
      by flow cytometric analysis revealed that exposure to bestatin at 5 to 20
      micrograms/ml for 72 h caused mild accumulation of NaUCC-4 cells in the G0/G1
      phase of the cell cycle, although no clear arrest was observed in any phase of
      cell cycle. In vivo antitumor activity of bestatin was examined using the NaUCC-4
      choriocarcinoma-xenografted nude mouse model. Tumor growth was significantly
      inhibited by daily i.p. administration of bestatin for 4 weeks at doses of 2 and
      20 mg/kg (p < 0.01 and p < 0.001, respectively), but not by 0.2 mg/kg as compared
      with control. No significant augmentation of NK activity or B cell mitogenicity
      in spleen cells taken from these NaUCC-4-hearing nude mice was observed following
      treatment with bestatin at either 2 or 20 mg/kg. These results indicate that
      bestatin inhibits the growth of NaUCC-4 choriocarcinoma in vivo as well as in
      vitro not via potentiation of effector cells but rather by its direct cytostatic
      activity, and suggest that bestatin may have an additional therapeutic property
      besides as a BRM for its use in the treatment of choriocarcinoma.

PMID- 8572607
TI  - Hemoglobin oxidative stress in cancer.
AB  - The role played by free radicals in carcinogenesis and their relationships with
      antioxidant pool and cancer have already been shown. Free radicals induce
      increased membrane permeability through membrane lipid peroxidation, protein
      oxidation and histamine release from mast cells. Free radicals also cause
      oxyhemoglobin oxidative stress which increases methemoglobin and hemichromes. For
      this reason, we studied the in vitro formation of methemoglobin at 0' and 90',
      dosed following the HPLC method, after oxidative stress of blood by means of
      acetylphenylhydrazine in 40 subjects with cancer and 40 healthy donors. The
      results showed that methemoglobin formation was highly significant in tumors as
      compared to controls (P < 0.0001). The statistical analyses we carried out showed
      that metHb formation is not affected by age, sex, smoking habit, red blood cell
      number, Hb, Ht or tumor staging. This makes us believe that free radicals alter
      erythrocyte membrane permeability and predenaturate oxyhemoglobin so that
      erythrocyte membrane becomes more susceptible to new oxidative stress. This
      caused the abnormal response we found. Our results clearly underline the role
      played by free radicals in tumorous disease and provide a successful and easy
      method to detect early, even in a pre-clinical stage, the presence of tumorous
      alterations in the human body.

PMID- 8572608
TI  - Inhibitory effects of phenolic carboxylic acid analogues on xanthine oxidase.
AB  - Nineteen phenolic carboxylic acid analogues were tested for the effects on
      xanthine oxidase inhibition. 2,2',4,'4'-Tetrahydroxybenzophenone and 2,3,4
      trihydroxybenzoic acid displayed the strongest activities (IC50 = 38.70 microM,
      IC50 = 90.16 microM respectively). Their apparent inhibition constants (Ki) were
      7.052 and 0.535 microM respectively, and induced mixed type and competitive type
      inhibitions respectively with respect to the substrate xanthine.

PMID- 8572609
TI  - Effect of potato starch, cornstarch and sucrose on aberrant crypt foci in rats
      exposed to azoxymethane.
AB  - Studies have shown that different kinds of carbohydrates are able to modify the
      development of colo-rectal cancer in animals as well as humans. In the present
      study with rats sucrose and two types of starches were investigated for their
      effects on the development of aberrant crypt foci (ACF), which have been proposed
      to represent preneoplastic lesions of colorectal cancer. Fifty-six three-week-old
      male Wistar rats were randomly assigned to four groups and dosed subcutaneously
      with AOM (15 mg/kg body wt) once a week for 2 weeks. At the end of the dosing
      period the animals were allocated to their respective diets. Group I was fed the
      basic diet; in Group II the carbohydrate pool in the diet was replaced by
      sucrose, in Group III by potato starch and in Group IV by cornstarch. Animals
      receiving the potato starch diet showed a statistically significant reduction in
      body weight gain. A statistically significantly lower number of ACF in all
      categories but small were demonstrated in animals given potato starch, and in
      addition an effect was seen in the relative distribution of ACF with fewer of the
      larger ACF. No effect of sucrose or cornstarch was seen. Explanations of the
      inhibitory effect in the potato starch group on the development of ACF could
      either be the lower daily caloric intake or the substantial amounts of resistant
      starch in the potato starch used.

PMID- 8572610
TI  - Distribution and changes of glycosaminoglycans in neoplasias of rectum.
AB  - The content, composition and physicochemical characteristics of
      glycosaminoglycans in human rectum and rectum carcinoma were investigated by
      chemical analyses, enzymic treatments, chromatographic and electrophoretic
      techniques. The overall glycosaminoglycan content was increased about 2 fold in
      neoplastic tissues compared to nonneoplastic tissues. The absolute amounts of
      chondroitin sulfate, hyaluronic acid and dermatan sulfate significantly increased
      but the amounts of heparan sulfate decreased in neoplastic tissues compared with
      nonneoplastic tissues. In addition an increased fraction of keratan sulfate and
      undersulfated chondroitin was identified in neoplastic tissues. HPLC analysis of
      chondroitinase AC and ABC digests showed a marked increase in delta di-6S and
      delta di-OS disaccharides in tumor chondroitin sulfate, revealing significant
      alterations on the sulfation pattern. The results indicate that specific
      glycosaminoglycan alterations occur in human rectum carcinoma and suggest that
      proteoglycan metabolism is also altered in this carcinoma.

PMID- 8572611
TI  - Effect of chlorpromazine and benzo[a]phenothiazines on heterotrophic auxin
      requiring and autotrophic auxin non-requiring tobacco tissue cultures.
AB  - Chlorpromazine and four benzo[a]phenothiazines were tested on the growth and
      auxin level of auxin requiring heterotrophic and auxin non-requiring autotrophic
      tobacco tissue cultures originating from transgenic plants. The auxin content was
      followed by the expression of GUS reporter gene connected with auxin inducible
      mass promoter. The benzo[a]phenothiazines had a higher antiproliferative effect
      than chlorpromazine. The exogenous auxin non-requiring autotrophic callus was
      more sensitive than the auxin requiring heterotrophic callus (Based on the low
      GUS activity). The reduced growth of auxin autotrophic tissues may be due to the
      low endogenous auxin content.

PMID- 8572612
TI  - A study of topoisomerase activity in human testicular cancers.
AB  - Topoisomerases are widely detected in rapidly proliferating cancer cells. Many
      anti-topoisomerase agents are utilized for cancer chemotherapy. Testicular
      cancers are highly chemotherapy sensitive, however, 10% of them are refractory to
      the standard regimen. To investigate the topoisomerase activities in human
      testicular neoplasms, we examined the activity of topoisomerase I (TopoI) and
      topoisomerase II (TopoII) in 29 testicular tumors. TopoI activity was observed
      irrespective of pathological types of the tumor (21/29). TopoII was detected in
      seminoma and teratocarcinoma (5/29). In our experience, seminoma was relatively
      sensitive to chemotherapy including anti-TopoII agents. Our results suggest that
      Topol inhibitors could be more effective against seminoma as well as the other
      types of testicular tumors.

PMID- 8572613
TI  - Induction of DNA fragmentation by tannin- and lignin-related substances.
AB  - A variety of tannin and lignin-related compounds were compared for their ability
      to induce nucleosome-sized DNA fragmentation (a biochemical hallmark of
      apoptosis), using agarose gel electrophoresis and a fluorescence activated cell
      sorter. Monomeric, dimeric, trimeric and tetrameric hydrolysable tannins induced
      nucleosome-sized DNA fragmentation in HL-60 cells, more potently than condensed
      tannins. The highest activity was detected in gallic acid, a component unit of
      tannins. Natural lignified materials, except for caffeic acid and its
      dehydrogenation polymer, showed much weaker activity. Protein-bound
      polysaccharide (PSK) was inactive. Gallic acid induced DNA fragmentation in four
      human myelogenous leukaemic cell lines, but not in human T-cell leukaemia and
      erythroleukaemia cell lines. Ca2+ depletion from the culture medium slightly, but
      significantly, reduced the apoptosis-inducing activity of gallic acid, but did
      not significantly affect that of tannic acid or caffeic acid. After treatment
      with gallic acid, intracellular Ca2+ concentration was significantly elevated.
      The apoptosis-inducing activity of polyphenols may further emphasize their
      medicinal efficacy.

PMID- 8572614
TI  - Cytogenetic, molecular and phenotypic characterization of the newly established
      renal carcinoma cell line KJ29. Evidence of translocations for chromosomes 1 and
      3.
AB  - The established non papillary human renal carcinoma cell line (RCC) KJ29 was
      submitted to a multiparametric characterization to evaluate its potential use for
      in vitro and in vivo studies. The cell line grows in vitro as monolayer as well
      as cell suspension. Cytogenetic analysis has shown a modal chromosome number of
      50 with some marker chromosomes, including rearrangements of chromosomes 1 and 3.
      The antigenic phenotype is characterized by co-expression of cytokeratin and
      vimentin, as well as expression of urothelium differentiation antigens, low
      levels of class II MHC antigens and no class I antigens. A differential
      expression of the VLA-3 integrin heterodimer has been detected between the
      adherent and non adherent cell population. The cell line which is highly
      tumorigenic in athymic mice displays expression of erb B-2 and c-met oncogenes
      and high expression of cell-cycle related and Ha-ras 1 genes.

PMID- 8572616
TI  - Intranuclear post-transcriptional down-regulation responsible for loss of a
      keratin differentiation marker in tumour progression.
AB  - Apparent loss of differentiation markers characterizes advanced malignant
      neoplasms. Post-transcriptional down-regulation of keratin message to levels
      undetectable with a partial cDNA probe to rat keratin K5 had been observed in
      anaplastic cells (T952/F7) derived from benign keratin-producing cells (A5P/B10)
      (1). The entire fifth introns of both the K5 and K6 genes were generated from rat
      genomic DNA by PCR to define expression of these closely related proteins.
      Sequencing of the PCR products revealed 84% homology in the K5 and K6 exon
      regions included, but absence of any homology in the introns. Active
      transcription of K5 could be demonstrated in the anaplastic cells with reverse
      transcription of nuclear RNA (RTn-PCR) by the presence of PCR-generated products
      confirmed by sequencing as unspliced and spliced transcripts of rat K5. In situ
      hybridization with ssDNA probes for the spliced message from this region of the
      K5 gene demonstrated a punctuate distribution in the cytoplasm of the benign
      cells and absence of any detectable message in the anaplastic derivatives, ssDNA
      probes for the unspliced transcript containing intron 5 and the same flanking
      exon sequences as the spliced probe detected transcription of hnRNA in the
      anaplastic cells as discrete signals confined to the nuclear compartment. These
      results show that failure to express mRNA for a differentiation marker in the
      cytoplasm of anaplastic cells can be due to a mechanism operating in the nuclear
      compartment after gene transcription and indicate that the mechanism functions
      shortly after splicing of the transcript.

PMID- 8572615
TI  - Induction by 5-aza-2'-deoxycytidine, an inhibitor of DNA methylation, of Le(y)
      antigen, apoptosis and differentiation in human lung cancer cells.
AB  - We recently developed a monoclonal antibody directed to carbohydrate antigen
      Le(y), BM-1/JIMRO, and found that expression of Le(y) antigen defined by BM
      1/JIMRO was associated with the process of apoptosis, but not with cell
      proliferation or necrosis. In the present experiments, we examined with BM
      1/JIMRO the effects of various differentiation inducers on the growth and
      expression of Le(y) antigen in human lung cancer A549 cells. We found that a
      specific inhibitor of methylation of DNA, 5-aza-2' deoxycytidine (ADC), could
      markedly induce expression of Le(y) antigen in association with induction of
      apoptosis and differentiation in the A549 cells. These results suggest that
      hypomethylation of DNA is involved in the molecular mechanisms of induction of
      Le(y) antigen, apoptosis and differentiation in the cells.

PMID- 8572618
TI  - Monoclonal anti-idiotypic antibodies as probes for common idiotopes shared by
      anti-"benzo(a)pyrene-like" IgA of cancer patients and rabbit anti-conjugated
      benzo(a)pyrene antibodies.
AB  - Anti-"benzo(a)pyrene [B(a)P]-like" IgA [referred as idiotypic antibodies (Abl)]
      from cancer patients' sera were found to react with conjugated B(a)P and a
      monoclonal anti-anti-conjugated B(a)P, internal image of conjugated B(a)P called
      AIB1 (referred to as Ab2 beta). These IgA were used to raise mouse monoclonal
      anti-idiotypic antibodies (Ab2). A monoclonal Ab2 called AIK1 was characterized
      as the internal image of a "B(a)P-like" structure. As shown by competitive
      experiments, AIK1 inhibited the reaction between Ab1 from a rabbit anti
      conjugated B(a)P serum- and its relevant internal image, AIB1. Furthermore, AIB1
      inhibited the reaction between AIK1 and anti-"B(a)P-like" IgA from cancer
      patients' sera. These observations confirmed the cross-reactivity between
      idiotypic determinants of human anti-"B(a)P-like" IgA and rabbit anti-conjugated
      B(a)P antibodies (Ab). This result was reinforced by a correlation between the
      anti-"B(a)P-like" IgA levels found in cancer patients' sera using indirect ELISA
      method with conjugated B(a)P, AIB1 and AIK1 coated on well-plates.

PMID- 8572617
TI  - Cell growth inhibitory effects of caulerpenyne, a sesquiterpenoid from the marine
      algae Caulerpa taxifolia.
AB  - Caulerpa taxifolia (Vahl) C. Agardh (Ulvophyceae, Caulerpales) is an algae of
      tropical origin that was accidentally introduced into the Mediterranean in 1984.
      Caulerpenyne (Cau) is the major metabolite present in Caulerpa taxifolia. This
      metabolite has previously been shown to be cytotoxic against cell lines in
      culture as in KB cells and fibroblasts from hamsters. Cau along with 6 other
      drugs representative of the major classes of anticancer products was tested
      against 8 cancer cell lines of human origin. Cau demonstrated growth-inhibitory
      effects in all cases with some variability between cell lines; this inter-cell
      variability was, however, less marked than that observed with the anticancer drug
      tested. Cells of colorectal cancer origin were the most sensitive to the presence
      of Cau with IC50 values of 6.1 and 7.7 microM. Increasing the duration of contact
      between Cau and the cells from 75 min to 29.5 hr did not improve the cytotoxic
      efficacy of this compound. When Cau was pre-incubated in the culture medium for
      from 7 to 83 min before being exposed to CAL 27 cells (head and neck cancer
      origin), there was a constant loss of cytostatic action of Cau as a function of
      Cau pre-incubation time. As the bovine serum albumin concentration increased in
      the culture medium, the concentration-response curves showed a constant shift
      towards the right, indicating a loss of cytostatic activity of Cau. In the
      presence of Cau, cells in culture clearly exhibited an early and marked shift
      into S phase followed by a blockade into the premitotic G2 M phase. Possible
      targets for CAU remain to be identified. Cau needs to be tested on tumor bearing
      animals to confirm this promising antiproliferative activity.

PMID- 8572620
TI  - In vitro reactivity to a protein-bound polysaccharide PSK of peripheral blood
      lymphocytes from patients with gastrointestinal cancer.
AB  - The effect of PSK, a protein-bound polysaccharide and an immunomodulator, on
      lymphocytes was examined in vitro for 36 patients with gastric cancer and 26 with
      colorectal cancer. Cultured lymphocytes with PSK at 100 micrograms/ml increased
      the level of DNA synthesis, as determined by the 3H-thymidine uptake, from 0.9 to
      3.0 fold, compared to the PSK non-treated cells. The increase was 1.36 +/- 0.46
      fold for the gastric cancer cases and 1.37 + 0.45 fold for the colorectal cancer
      cases, and these levels were significantly the finding of 1.93 + 0.55 fold for a
      control group consisting of 15 healthy volunteers (P < 0.01). When the 1.3 fold
      increase of 3H-thymidine uptake was defined as the PSK-reactive group, 52.8%
      (19/36) of the patients with gastric cancer and 50.0% (13/26) for colorectal
      cancer were found in the PSK-reactive group. The PSK-reactive group demonstrated
      no relation to the age and sex of the patients, tissue differentiation type or
      tumor advancement. Our findings thus show that the in vitro activation of
      lymphocytes by PSK can help identify the candidates with either gastric or
      colorectal cancer who are the best suited to undergo immunochemotherapy including
      treatment with PSK.

PMID- 8572619
TI  - Tumour targeting of the anti-ovarian carcinoma x anti-CD3/TCR bispesific
      monoclonal antibody OC/TR and its parental MOv18 antibody in experimental ovarian
      cancer.
AB  - The anti-tumour x anti-T-cell bispecific monoclonal antibody (biMAb) OC/TR is a
      biologically produced biMAb combining the anti-ovarian carcinoma activity of the
      MOv18 MAb with anti-CD3/T-cell receptor (TCR) complex activity. In this study,
      the in vitro binding characteristics of the OC/TR biMAb and its tumour targeting
      potential in nude mice with Hela tumours was studied. Scatchard analysis revealed
      that the affinity constant of the biMAb was 7 times lower than the affinity of
      the parental MOv18 antibody. Uptake of the OC/TR antibody in the Hela xenografts
      in nude mice was significantly higher than the tumour uptake of an irrelevant
      control antibody, indicating that the radioiodinated OC/TR biMAb specifically
      localized in the tumour xenografts. However, tumour uptake was significantly
      lower than the tumour uptake of the parental MOv18 antibody. This reduced tumour
      uptake most likely is a result of its reduced affinity. We conclude that, despite
      the loss of bivalent tumour cell binding, the biMAb OC/TR can still specifically
      localize in tumours. This indicates that the first prerequisite of an effective
      therapeutic approach using systemically applied biMAb can be met. Whether the
      interaction with human T-cells will affect the tumour targeting potential of the
      biMAb in patients remains to be investigated.

PMID- 8572622
TI  - Natural interferon-beta and tamoxifen in hormone-resistant patients with advanced
      breast cancer.
AB  - Tamoxifen (T) is the mainstay of hormonal treatment and is able to give high
      response rates in selected postmenopausal women with advanced breast cancer
      (ABC). Nevertheless, even in responders, invariably resistance to hormones is
      developed. In a previous paper we reported that in a subset of patients (pts)
      with metastatic breast cancer the resistance to the antiestrogen could be
      overcome by pretreatment with natural interferon-beta (nIFN-beta) followed by the
      association of nIFN-beta and T. In the present study we adopted a treatment
      schedule employing nIFN-beta (3 x 10(6) IU/day im three times a week) and T (60
      mg/day) concurrently in 30 pts with ABC progressive to previous treatment with T
      (30 mg/day). We obtained a 13% response rate with a median duration of response
      of 8 months (range 4-16 m). All the responses occurred in pts whose disease
      progressed after an initial response to T. Stabilisation of disease was observed
      in 37%. Toxicity was mild. In our opinion the use of the combination T plus nIFN
      beta in the treatment of breast cancer remains investigational and the optimal
      scheduling still undetermined.

PMID- 8572621
TI  - Prognostic significance of serum CA 242 in pancreatic cancer. A comparison with
      CA 19-9.
AB  - The prognostic value of the novel tumour marker CA 242 was studied in 175
      patients with pancreatic cancer and the results were compared with those of CA 19
      9. Preoperative serum levels of CA 242 and CA 19-9 were determined by
      commercially available assays. Patients were classified according to UICC TNM
      stage, and divided into three groups of resectable, non-resectable and advanced
      disease. The lowest cut-off levels that divided patients into groups with
      significant difference in survival were calculated. Patients with resectable
      disease and preoperative CA 242 below 25 U/ml had a significantly better
      prognosis than those with a higher level (p < 0.05). The corresponding cut-off
      values were 100 U/ml in non-resectable (p < 0.05) and 3500 U/ml in advanced
      disease (p < 0.05). It is noteworthy that the overall survival rate of patients
      who underwent resection for cure, but had a high preoperative CA 242 level,
      approached that of patients with non-resectable disease. In multivariate
      analysis, only resectability (p < 0.0001) and preoperative serum CA 242 level (p
      = 0.01) were independent prognostic factors. If TNM-stage was used instead of
      resectability, the results were similar (stage p < 0.0001, CA 242 p = 0.006).
      When CA 242 was excluded from the model, preoperative serum CA 19-9 level
      approached the borderline of significance as an independent prognostic factor (p
      = 0.07). In conclusion, the preoperative serum level of the novel tumour marker
      CA 242 is an independent prognostic factor in pancreatic cancer. CA 242 yielded
      more prognostic information than CA 19-9.

PMID- 8572623
TI  - Induction of MxA mRNA in patients with neuroendocrine tumors after interferon
      treatment. Lack of correlation with antitumor response.
AB  - We have investigated the possibility of using induction of MxA mRNA in patients
      with neuroendocrine tumors undergoing interferon-alpha(IFN-alpha) treatment as a
      predictive test for antitumor effect. A total of 122 patients with various types
      of neuroendocrine tumors were included in the study. Blood samples were drawn 12
      hours after administration of either recombinant or natural IFN-alpha for
      analysis of induction of MxA mRNA in peripheral blood leukocyte (PBLs). Total RNA
      was isolated and slot-blot hybridization was performed using a MxA cDNA fragment
      as a probe. All patients displayed induction of MxA mRNA. Out of 13 untreated
      patients, 4 had MxA mRNA as well as 2 out of 11 patients treated with
      somatostatin analogue. All IFN-alpha treated patients showed induction of MxA
      mRNA and there was no difference between patients demonstrating partial
      remission, stable disease or progressive disease. Moreover, there was no
      difference between recombinant or natural leukocyte IFN-alpha in the ability to
      induce MxA mRNA. Six patients developed neutralizing IFN-alpha antibodies with 1
      patient presenting a tire of 3200 NU/ml. Development of neutralizing antibodies
      did not abrogate the induction of MxA mRNA, but in 3 patients with high antibody
      titres the antitumor effect was lost. We therefore conclude that IFN-alpha is
      able to induce MxA mRNA in PBLs from patients with neuroendocrine tumors but we
      could not find any correlation with the therapeutic outcome. Furthermore,
      development of neutralizing IFN-alpha antibodies, although abrogating the
      antitumor effect, might not block the antiviral activity.

PMID- 8572624
TI  - Early hematological toxicity of adjuvant perioperative intraportal and
      intravenous chemotherapy with fluorouracil, mitomycin and heparin in colorectal
      cancer. Swiss Group for Clinical Cancer Research.
AB  - BACKGROUND: From 1987 to 1993 the Swiss Group for Clinical Cancer Research (SAKK)
      performed a randomized phase III adjuvant trial in patients with colorectal
      adenocarcinoma with the objective of comparing intraportal versus intravenous
      perioperative chemotherapy. PATIENTS AND METHODS: Patients younger than 75 years
      had a curative en bloc resection of their cancer and were then randomized into
      three arms: 1. adjuvant perioperative portal liver infusion with fluorouracil,
      mitomycin and heparin, 2. adjuvant subclavian intravenous infusion with the same
      regimen and 3. no adjuvant treatment. The hematological toxicity was evaluated by
      hemoglobin determination and leucocyte and thrombocyte counting before and during
      ten days after surgery. RESULTS: Hemoglobin showed a median decrease of 22% in
      the control group. This decrease is aggravated significantly by 3% through the
      chemotherapy. Leucocytes showed a median decrease of 7% in the control group.
      Perioperative chemotherapy caused a significantly higher median drop; 23% when
      given into the liver through the portal vein and 34% when given systemically
      through a subclavian catheter. Thrombocytes revealed a median decrease of 25% in
      the control group. Chemotherapy was not associated with a significant additional
      drop. CONCLUSIONS: Adjuvant perioperative chemotherapy with fluorouracil,
      mitomycin and Heparin as given in this study is associated with a significant
      mild drop in hemoglobin and leucocytes during the first 10 postoperative days. If
      drug dose increases are planned in future trials the addition of hematopoietic
      growth factors might be considered.

PMID- 8572625
TI  - Locoregional immunotherapy of malignant ascites by intraperitoneal administration
      of OK-432 plus IL-2 in gastric cancer patients.
AB  - The clinical efficacy of intraperitoneal administration of OK-432 plus
      interleukin-2 (IL-2) for treating malignant ascites was evaluated in gastric
      cancer patients. Ten KE of OK-432 and 200,000 Jurkat units of IL-2 were
      intraperitoneally administered in tandem in the order given on alternate days at
      paracentesis. Of the 22 evaluable patients, 18 (81%) developed complete or
      partial responses, showing a cytologic disappearance of cancer cells and decrease
      of ascites. More than 50% of the patients obtained positive responses within 2
      weeks after the initial administration of the drugs. Improvements of performance
      status and clinical symptoms such as abdominal fullness, followed by restoration
      of oral food intake and prolongation of survival time were observed in responders
      treated with OK-432 plus IL-2. Flow cytometric analysis demonstrated a
      predominant increase of the CD3+CD4+ cells, especially of the CD4+CD45RA- subset
      in the peritoneal cavity of the responders. Cytotoxicity assay after negative
      selection of the CD4+ cells with the antibody and complement revealed that the
      CD4+ subset possessed cytotoxic activity against autologous tumor cells. The
      results suggest that intraperitoneal administration of OK-432 plus IL-2 may not
      be only a practical but also an effective protocol for treating malignant ascites
      in gastric cancer patients.

PMID- 8572626
TI  - Intraperitoneal infusion of recombinant human tumor necrosis factor and
      mitoxantrone in neoplastic ascites: a feasibility study.
AB  - In cancers limited to the abdominal cavity the intraperitoneal administration of
      antineoplastic drugs could be the treatment of choice because of both the limited
      systemic toxicity and the pharmacokinetic advantage. Preclinical studies suggest
      that the combination of Tumor Necrosis Factor (TNF) and mitoxantrone have a
      synergistic effect. On this basis, we conducted a study to verify the feasibility
      of the intraperitoneal administration of these drugs in patients with malignant
      ascites. Cohorts of three patients were treated with a fixed dose of mitoxantrone
      (6 mg/m2) and escalating doses of TNF (from 60 up to 200 mcg/m2),
      intraperitoneally, given for two hours once a week for at least four weeks.
      Seventeen patients with malignant ascites entered into the study. All but two
      patients received the planned four cycles. Sixty-six cycles were given. The most
      common side effects were fever (21-44% of cycles), chills (8-44%), fatigue (19
      33%), loss of appetite (17-57%), malaise (25-43%), myalgia (33%), pain injection
      (25-83%), nausea/vomiting (33-64%). Severe fatigue, malaise and anorexia were
      observed only at doses of 200 mcg/m2 of TNF. Weekly intraperitoneal
      administration of mitoxantrone (6 mg/m2) and TNF (200 mcg/m2) is a feasible
      regimen with acceptable toxicity. The activity of this combination should be
      studied in properly designed phase II trials.

PMID- 8572627
TI  - Extrachromosomal human papillomavirus (HPV) in multiple myeloma and monoclonal
      gammopathy of unknown significance (MGUS) patients.
AB  - There are over 75 different types of human papillomavirus (HPV). Certain types
      have a strong association with cervical dysplasias. We have previously identified
      HPV in a chronic benign plasma cell tumor of the cervix, multiple myelomas and
      monoclonal gammopathy of unknown significance (MGUS). Since HPV is believed to
      replicate only in differentiated keratinocytes, we examined these tissues to
      identify any possible replicative forms. We used genomic Southern analysis and
      PCR to determine the physical state of the virus. We identified episomal forms in
      both the malignant and premalignant stages of B cell diseases. These data provide
      definitive proof of episomal HPV sequences in lymphoid tissues and question the
      current dogma that HPV is permissive only in terminally differentiated squamous
      cells.

PMID- 8572628
TI  - Serum ostase in the follow-up of breast cancer patients.
AB  - The present study was carried out on 152 patients divided into three groups: A)
      73 underwent radical surgery for breast carcinoma without signs of metastases; B)
      31 patients with radiologic and scintigraphic evidence of bone metastases
      originating from malignant mammary neoplasia (14 with only one and 17 with two or
      more localizations); C) 48 affected by simple mammary cysts. No patients had a
      previous history of primary or secondary bone pathologies or renal, hepatic or
      endocrine ones. Besides this, no patient took drugs influencing the metabolic
      turnover of the bony tissue in the three months preceding the study. After
      surgery all patients underwent standard clinical and laboratory follow-up, the
      latter including, every 3 months, the evaluation of serum CA 15.3, CA 27.29 MCA,
      and ostase. The ostase cut-off, obtained by the statistical elaboration of the
      serum values of the 48 patients with benign mammary cysts and the 73 disease free
      patients, was 17 microg./L. The mean concentration in the three groups and two
      subgroups was: 13.76 microg./L (patients without metastases), 31.84 (patients
      with metastases), 18.4 (limited bony metastases), 40.04 (diffused bony
      metastases) and 5.36 (mammary cists). The diagnostic sensitivity of ostase proved
      superior to that of CA 15.3 (84% vs 75%) except when considering the subgroup
      with limited metastases (71.4% vs 72.7%), while the specificity was similar
      (around 78%). CA 27.29 and MCA were not useful as markers of metastasis. In a
      longitudinal-perspective study it was possible periodically to test these markers
      in 13 patients, at first, disease free and then with signs of bone progression
      evidence by skeletal scintigraphy. In 11 of these patients ostase and CA 15.3
      showed increased values, an average 136 and 131 days respectively, before
      instrumental evidence of progression. None of the 13 patients, at the time of
      bone progression diagnosis, showed clinical, laboratory or instrumental signs of
      disease in other organs. The precocity of the serum increase of ostase could have
      a triple role: 1) accomplishment of a closer follow-up in patients at "high risk"
      of bone disease; 2) aid in the interpretation "in a neoplastic sense" of an
      "uncertain image of hypercaptation"; 3) accomplishment of a supporting or
      specific oncology treatment at an earlier stage which may be of some advantage as
      regards quality of life.

PMID- 8572629
TI  - Serum bone alkaline phosphatase in the follow-up of skeletal metastases.
AB  - The efficacy of bone alkaline phosphatase (ALP) isoenzyme measurement, using a
      lectin precipitation method, in confirming metastatic sites was assessed in 65
      patients with cancer and skeletal (n = 44), hepatic (n = 15) or lymph node (n =
      6) metastases; the control group consisted of 33 healthy adults. In all subjects,
      total ALP activity and osteocalcin were also assayed. Our results confirm that
      isoenzyme analysis is more specific than total enzymatic activity measurement in
      the identification of bone metastases: the mean for total ALP values was
      increased in all patients, while significantly high mean values of bone fraction
      (p < 0.05 by ANOVA) were observed only in patients with bone secondaries. In the
      serial monitoring of 9 patients with skeletal metastases, bone ALP values
      correlate with pain symptomatology: a progressive decrease in bone isoenzyme
      activity was observed in patients with a complete remission of pain after
      radiotherapy, while a progressive increase in activity was observed in the
      presence of increased bone pain. The measurement of bone isoenzyme activity is
      useful in screening for skeletal metastases; levels appear to correlate with the
      course of bone symptomatology, thus providing useful objective evidence of
      response to treatment.

PMID- 8572630
TI  - Mitomycin C, methotrexate, and vincristine with medroxyprogesterone acetate or
      prednisolone for doxorubicin resistant advanced breast cancer--a randomized
      control study.
AB  - This randomized study was designed to compare the efficacy and toxicity of MMV
      chemotherapy (mitomycin C(MMC), methotrexate (MTX) and vincristine(VCR)), MMVM
      (MMV+medroxyprogesterone acetate(MPA)) and MMVP (MMV+prednisolone(P)), and to
      evaluate potential additional effects of MPA or P to the chemotherapy in
      doxorubicin (ADR)-refractory cancer patients. A total of 108 advanced breast
      cancer patients who had been resistant to ADR or who had relapsed after response
      were randomized to the three treatment arms: MMC 4mg/m2, MTX 35mg/m2 and VCR
      0.7mg/m2, i.v., on days 1 and 8; repeated every 3 weeks. MPA 1,200 mg/day or P
      10mg/day was given orally in the MMVM and MMVP arms, respectively. An interim
      analysis showed that the response to MMV was marginally significantly lower than
      the other groups; entry to the arm was thus interrupted. 102 patients were
      evaluable. Totally, response rates of 9.5%(2/21) in MMV, 37.5%(15/40) in MMVM and
      29.2%(12/41) in MMVP were obtained. There was a significant difference in the
      response between the MMVM and MMV arms (p = 0.0206), and a marginal difference
      between MMVP and MMV (p = 0.0784). Although overall survivals in the 3 groups
      were equivalent, the time to progression of patients treated with MMVM and MMVP
      was shown to be significantly longer than MMV patients. Hematological adverse
      effects, especially thrombocytopenia, were significantly diminished by the
      addition of hormones, particularly MPA, to the chemotherapy, thus increasing
      total doses of chemotherapeutic agents. It was shown that in ADR-resistant
      cancers MMVM had an effect equivalent to that in ADR-sensitive breast cancers.
      The authors conclude that MMVM may be a candidate for a noncross resistant
      regimen for ADR-resistant cancers, as well as an effective 2nd line
      chemoendocrine treatment of advanced breast cancer.

PMID- 8572631
TI  - A treatment planning system for stereotactic radiotherapy.
AB  - Stereotactic radiotherapy to treat neoplastic lesions or artero-venus
      malformations in the brain may be accomplished with a linear accelerator by
      performing several non-coplanar arcs of irradiation with a highly collimated beam
      focused on a fixed point. This paper introduces a system to perform treatment
      planning. It is based on a Personal Computer and allows the acquisition,
      reconstruction and visualization of the target volume, within the brain, from CT
      (Computerized Tomography) or MR (Magnetic Resonance) images, and then it permits
      calculation and visualization of a 3-D (three-dimensional) dose distribution due
      to small photon beams. The performances of the system and its use in a practical
      case are described.

PMID- 8572632
TI  - Flow cytometric analysis of DNA ploidy and cell proliferation activity in
      colorectal carcinoma.
AB  - The aim of this study was to evaluate the relationship between DNA ploidy,
      proliferative activity and other prognostic factors and the survival of patients
      with colorectal cancer. 45 patients were prospectively investigated for 6 years.
      Fresh multiple samples for flow cytometric analysis of DNA content were collected
      during surgical resection of primary tumor. A 42% frequency of aneuploidy was
      observed with a median DNA index value of 1.54. The proliferative activity
      (%S+G2M cells) was higher in the aneuploid cell sub-population (28.6%) compared
      to the diploid counterpart (22.7%)(p = 0.05). No significant relationship between
      DNA ploidy and tumor site, Dukes' stage, histological type, grading age or sex
      was observed. No correlation between DNA ploidy and survival was demonstrated,
      including in the analysis of patient subsets according to stage. No additive
      prognostic information was obtained from a breakdown analysis as a function of DI
      values, percentages of aneuploid cells and proliferative activity. This study
      suggests that flow cytometric content analysis lacks prognostic value in
      colorectal carcinoma.

PMID- 8572633
TI  - Preoperative serum intercellular adhesion molecule-1 (ICAM-1) and E-selectin
      (endothelial cell leukocyte adhesion molecule, ELAM-1) in patients with
      epithelial ovarian cancer.
AB  - The serum levels of intercellular adhesion molecule-1 (ICAM-1) and E-Selectin
      (endothelial cell leukocyte adhesion molecule, ELAM-1) were retrospectively
      measured in serum samples drawn at diagnosis from 66 patients with epithelial
      ovarian cancer and 128 patients with benign ovarian masses. The preoperative
      serum ICAM-1 levels were higher in the former group (p < 0.0001), while serum E
      Selectin concentrations were similar in the two groups (p = NS). Among patients
      with epithelial ovarian cancer, neither serum ICAM-1 nor E-selectin levels
      correlated with FIGO stage and with histologic type. The serum assay of ICAM-1
      and E-Selectin seems to have limited value in the management of patients with
      epithelial ovarian cancer.

PMID- 8572634
TI  - Granisetron-dexamethasone combination for multiple day cisplatin.
AB  - Thirty-four, patients being given polychemotherapy schedules including cisplatin
      at the dose of 20 mg/sm for 5 days entered an antiemetic protocol with
      granisetron and dexamethasone at the doses of 3 mg and 8 mg respectively, both
      administered i.v. before cisplatin. A complete response (no episodes of vomiting)
      and a major response (< or = 2 episodes of vomiting) were observed in 14 and 12
      patients respectively; the toxicity of the antiemetics was mild. It is concluded
      that the granisetron dexamethasone combination is able to achieve a high rate of
      antiemetic control in the special set of multiple day cisplatin treated patients.

PMID- 8572635
TI  - The influence of obesity on the disease-free survival in primary breast cancer.
AB  - Hyper-estrogenism is more common in obese than in non-obese women. Consequently
      obesity has been shown to increase the risk of hormone department tumors. Some
      investigators have claimed that obesity at the time of primary treatment may be
      an independent prognostic factor for breast cancer, but this issue is still
      controversial. Therefore, we conducted a retrospective analysis to assess the
      influence of obesity at the time of primary treatment on disease-free survival
      (DFS). Obesity was defined as an excess of more than 25% of ideal weight
      according to Broca's index ([Height (cm) -100])-10%). The Cox-model was used for
      multivariate analysis. Mean follow-up was 61 (range 6-126) months. 295 (62.3%)
      patients were classified as of normal weight and 178 (37.6%) as obese. Mean
      excess of ideal weight was 8.9 kilograms (kg) in premenopausal and 13.9 kg in
      postmenopausal patients (non-parametric t-test p < 0.00001). Patients with tumor
      size < 20mm, 20-50mm and > 50mm had a means excess of the real weight of 10.6kg,
      12.5kg and 16.1kg, respectively (non-parametric t-test p < 0.0001). Percentual
      excess of real weight compared to ideal weight was 22.4 [+/-21.2] kg in patients
      without recurrence and 21.5 [+/-21.9] in patients with recurrent disease
      (nonparametric t-test p = 0.7256). Univariate analysis revealed no significant
      association between obesity and the DFS. Multivariate analysis identified
      axillary lymph node involvement as the only statistically significant prognostic
      factor for disease-free survival (RR 1.55; 95%-confidence interval 1.02-2.36;
      p:0.0368). Because of the high correlations and node-status, tumor size and
      histological grading, the other factors failed to be prognostically relevant in
      this analysis. Obesity was not found to influence DFS of patients with primary
      breast cancer and is therefore unlikely to constitute an independent prognostic
      factor. It may, however, contribute to delayed diagnosis, since a significant
      proportion of obese patients were diagnosed with local advanced disease.

PMID- 8572636
TI  - Immunological alterations induced by adjuvant treatment of postoperative colon
      carcinoma Duke's B or C with levamisole in combination with 5-FU.
AB  - BACKGROUND: Postoperative 5-FU combined with levamisole increases 5 year survival
      in colon cancer patients (Duke C) by 30% (1). In order to investigate the
      potential immunological mechanism, we determined lymphocyte subtypes and markers
      of immune activation in 22 patients before and during one year of postoperative
      adjuvant treatment. METHODS: Before and regularly during treatment, according to
      the scheme described by Moertel (1), major lymphocyte subsets were quantified by
      flow cytometry. Serum neopterin, soluble IL2-receptors, beta 2-microglobulin, TNF
      alpha and interferon-gamma were determined by Elisa. RESULTS: The CD4/CD8 ratio
      increased significantly after levamisole was added to the treatment, as did the
      levels of soluble IL2-receptors. The percentages of T-cells expressing the
      interleukin 2 receptor followed a similar trend. The levels of neopterin tended
      to decrease during the combined treatment course. This was paralleled by a
      progressive fall in the proportion of T-cells expressing HLA-DR. CONCLUSIONS: The
      treatment induced significant and consistent alterations in major immunological
      mediators and lymphocyte subtypes. It remains to be established whether these
      changes are related to the therapeutic effect.

PMID- 8572638
TI  - Infiltrating ductal carcinoma of the breast: extensive intraductal component has
      no impact on lymph node involvement and survival.
AB  - The extensive intraductal component (EIC) in infiltrating ductal carcinoma (IDC)
      was reported to be a predictor of local recurrence. We investigated the influence
      of this histopathological parameter on nodal status and overall survival. In 115
      patients suffering from an IDC with tumor stage FIGO I and II, 35 were EIC
      positive. We did not find a correlation with the nodal status. The mean follow up
      was 73 (+/- 38) months. EIC showed no influence on overall survival. Based on our
      findings, the presence of EIC is not a criterion for therapeutic decisions in
      IDC.

PMID- 8572637
TI  - Prognostic evaluation of DNA flow cytometry and histo-morphological criteria in
      renal cell carcinoma.
AB  - Clinical, histological and flow cytometric data (DNA content, S phase fraction)
      were related to clinical behaviour in 124 patients with renal cell carcinoma
      followed up for more than nine years. 69% of the tumours were diploid and 31%
      were aneuploid. The S phase fraction (SPF) ranged between 0.5% and 17.2% and the
      mean (s.e.) was 3.8 (0.3)%. The SPF was higher in aneuploid than in diploid
      tumours [mean, s.e., 2.6 (0.2)% vs. 6.4 (0.6)%, p < 0.001]. DNA ploidy was not
      related to any of the analysed features, while S phase was related to nuclear
      grade (p < 0.001), combined nuclear grade (p = 0.0025) and node metastasis at
      diagnosis (p = 0.036). In a multivariate analysis, the recurrence-free survival
      of M0 tumours was independently predicted by combined nuclear grade (p < 0.001),
      M/V index (p = 0.007), T-category (p = 0.011) and location (left/right) (p =
      0.022). Survival in the entire cohort was independently related to T-category (p
      < 0.001), M/V index (p = 0.001) and DNA ploidy (p = 0.050). Survival of M0
      tumours was independently related to M/V index (p < 0.001), DNA ploidy (p =
      0.005) and T-category (p = 0.003). DNA aneuploidy was related to favorable
      disease outcome both in univariate and multivariate analysis in the entire series
      and in all the subanalyses. The results suggest that genomic instability in
      aneuploid cells may reduce their capacity to resist immunological host response
      or aneuploid tumours may be more sensitive to treatment.

PMID- 8572639
TI  - Efficacy of two oral dose regimens of granisetron.
AB  - BACKGROUND: Most chemotherapic treatments are carried out on an outpatient basis.
      In such patients the prevention and control of emesis is important. Granisetron
      is a specific and extremely potent 5-HT3 antagonist available as an oral
      formulation. We have carried out an open randomized crossover study in patients
      receiving moderately emetogenic chemotherapy. MATERIALS AND METHODS: 30 patients
      were randomized to receive one of the two oral dose regimens of GRAN. Treatment A
      = 1 mg of GRAN initially and 12 hours after the first; treatment B = a single 2
      mg dose of GRAN. RESULTS. An overall good response for vomiting was reached in
      70% and 86.7% respectively of patients receiving treatments A and B (p = 0.0625).
      Good response to nausea was reached in 73.3% of the patients with treatment A and
      in 76.7% with treatment B (p = 1). 68.3% of patients did not record chemoinduced
      emesis. CONCLUSION: We believe that oral GRAN alone is an active and safe drug
      for the prevention of acute chemoinduced emesis.

PMID- 8572640
TI  - Usefulness of lymphocyte subset change as an indicator for predicting survival
      time and effectiveness of treatment with the immunopotentiator lentinan.
AB  - The usefulness of lymphocyte subset change as an indicator for predicting
      survival time and the effectiveness of combined treatment with an
      immunopotentiator, lentinan, and carboplatin (CBDCA) were investigated. Of 13
      patients with advanced unresectable cancer entered in this study, 9 were
      administered 2 mg/body lentinan and 450 mg/m2 CBDCA, and 4 were administered a
      single modality of CBDCA. The mean survival time of all 13 cases was 9.89 months.
      Lymphocyte subsets of CD11(-)CD8(+), CD11(+)CD8(+), CD57(-)CD16(+) and
      CD57(+)CD16(+,-) were measured by two-color flow cytometry. In five cases
      surviving longer than 9.89 months, CD11(-)CD8(+)/CD11(+)CD8(+) on post-treatment
      showed an increase two-fold higher than on pre-treatment, but in all cases
      surviving less than 9.89 months the rate on post-treatment did not increase two
      fold higher than on pre-treatment. The mean (1.78) of (post-treatment/pre
      treatment) ratios of CD57(-)CD16(+)/CD57(+) in long survival cases was
      significantly higher (p < 0.01) than that (0.46) in short survival cases.
      Moreover, the mean of (post-treatment/pre-treatment) ratios of CD11(
      )CD8(+)/CD11(+)CD8(+) and CD57(-) CD16(+)/CD57(+) showed a good correlation with
      survival time. These results indicate that changes of lymphocyte subsets of
      killer T cell/suppressor T cell and natural killer cell on posttreatment compared
      to pre-treatment are clinically useful indicators for predicting and monitoring
      the effectiveness of combined treatment with lentinan and CBDCA.

PMID- 8572642
TI  - Proliferating cell nuclear antigen (PCNA) as a prognostic factor for colorectal
      cancer.
AB  - PCNA (proliferating cell nuclear antigen) is a cell cycle related protein that is
      maximally elevated in late G1 and S-phase of proliferating cells. 114 biopsy
      specimens of colorectal cancer were immunolabeled with PC 10 which specifically
      recognizes PCNA; Dukes' staging and histological grading were estimated for each
      case. All patients were followed-up for at least 60 months or to death. All data
      were analysed by the computer program NCSS (Number Cruncher Statistical System).
      According to the results, PCNA-index may be considered an independent prognostic
      factor for colorectal cancer; it may also be helpful in supporting the
      therapeutic strategies based only on Dukes' stage.

PMID- 8572641
TI  - Mitoxantrone in elderly women with advanced breast cancer: a phase II study.
AB  - Comorbidity has important implications in older breast cancer patients. Whether
      elderly patients are more likely to have a decreased tolerance to antineoplastic
      agents is still a question of debate. Chemotherapy-naive women with metastatic or
      locally advanced breast cancer aged > or = 68 years entered a phase II trial of
      Mitoxantrone given day 1 q 21 days. The dose of the drug was dependent on
      performance status (PS) and number of "minor" comorbid conditions: patients with
      ECOG PS = 2 and/or > or = 2 comorbid conditions received 10 mg/m2 and those with
      PS < 2 and < 2 comorbid conditions received 14 mg/m2. Twenty-seven patients,
      median age 77 years (range 68-86), received a median number of 5 courses (range 1
      9). All 27 patients were evaluable for toxicity and 23 cases (patients receiving
      at least 3 courses) were evaluable for response. Partial response was observed in
      6/23 cases (26%) and median duration of response was 6 months (range 3-9). Median
      overall survival was 8 months (range 2-34). Among cases receiving 10 mg/m2, 4 PR,
      4 SD and 2 P were observed and in cases treated with 14 mg/m2, 2 PR, 5 SD and 6 P
      occurred. Treatment was well tolerated and no grade 4 toxicity was encountered.
      Mitoxantrone is an effective and well-tolerated regimen in elderly breast cancer
      patients presenting with comorbid conditions.

PMID- 8572644
TI  - Basaloid carcinoma and keratinizing squamous cell carcinoma of the vulva: a case
      of two primary carcinomas.
AB  - Basaloid carcinomas of the vulva have been reported to occur mostly in young
      women and are often associated with Human Papillomavirus (HPV) infection, whereas
      older women mostly suffer from keratinizing squamous cell carcinomas unassociated
      with HPV. The rare case of a 75 year old woman coincidentally suffering from a
      basaloid carcinoma and a keratinizing squamous cell carcinoma of the vulva is
      reported. With in situ hybridisation, hybrid capture and immunohistochemical
      methods we searched for HPV and expression of cytokeratin AE1/AE3, cytokeratin
      HMW and cytokeratin 8, 18, 19. HPV was not found in either of the carcinomas.
      Cytokeratin HMW showed a focal staining reaction in the keratinizing squamous
      cell carcinoma and no expression in the basaloid carcinoma. Immunohistochemical
      staining reaction for cytokeratin AE1/AE3 was found in both tumors with the same
      staining pattern. Cytokeratin 8, 18, 19 was not detected in either of the two
      carcinomas.

PMID- 8572643
TI  - Phase II trial of mitoxantrone, doxifluridine and medroxyprogesterone acetate as
      second-line treatment for anthracycline-resistant metastatic breast cancer.
AB  - Sixteen patients with anthracycline resistant metastatic breast cancer were
      treated with a combination of mitoxantrone (MIT), doxifuridine (5'-DFUR) and
      medroxyprogesterone acetate (MPA). The median dose of anthracyclines was 360 mg
      (range 20-540 mg). Eligible patients received 7.0 mg/m2 of MIT every four weeks
      600 mg of 5'DFUR were given orally every day. Eight (50.0%) out of 16 patients
      showed partial response. Six (54.5%) out of 11 bone lesions, 4 (80.0%) out of 5
      lung lesions and 1 (20.0%) out of 5 soft tissue lesions responded to this
      treatment. The median response duration was 26 weeks (range 4-52). Hematological
      and gastrointestinal toxicity were tolerable. Alopecia was not observed.
      Tachycardia was noted in patients receiving more than 80 mg of MIT; however,
      digitalis controlled the symptom. The combined treatment with MIT is useful for
      anthracycline-resistant metastatic breast cancer.

PMID- 8572645
TI  - Prognostic significance of C-erbB-2 and hormone receptors' status in human benign
      and malignant breast lesions.
AB  - In order to investigate the prognostic significance of c-erbB-2, estrogen
      receptors (ER) and progesterone receptors (PgR), an immunohistochemical staining
      was performed on 330 tissue sections from paraffin blocks of 50 fibrocystic
      diseases and 40 ductal adenocarcinomas N.O.S. type, grade II (20 with lymph node
      metastases (L.N.M)). The positivity for c-erbB-2 was considered only in the
      cytoplasmic membrane, while for ER and PgR in the nucleus of epithelial cells.
      All markers showed a heterogenous pattern of staining. Our results imply that
      benign lesions were negative for c-erbB-2 and hormone receptors except for
      limited areas with papillary proliferations. Elevated expression of these markers
      was noted in the adenocarcinomas. No significant difference was observed between
      the percentage of all markers in primaries and L.N.M. lesions. Hormone receptors'
      status showed no significant correlation with c-erbB-2 expression. Our results
      suggest that c-erbB-2, ER and PgR, especially when combined with
      clinicopathological parameters, may show some prognostic usefulness in breast
      disease.

PMID- 8572647
TI  - Increased serum levels of basic fibroblast growth factor (bFGF) are associated
      with progressive lung metastases in advanced renal cell carcinoma patients.
AB  - Basic fibroblast growth factor (bFGF) has been detected in body fluids of
      patients with various malignancies including renal cancer. Cytoplasmatic
      expression of bFGF in primary renal cell carcinoma cells has been reported
      recently to correlate with an impaired patient survival. In the present study, we
      analysed the statistical association of spontaneous serum bFGF levels in 23
      patients with advanced renal cell carcinoma and progressive metastasis in
      different organ sites. Increased bFGF serum levels (>90% percentile for healthy
      donors i.e., > 14 pg/ml) were found in eight patients (35%) with a mean of 24.1
      pg/ml. All patients in this subgroup presented with progressive pulmonary
      metastases at the time of sample collection (p < or = 0.007). In a total of
      fifteen patients exhibiting progressive pulmonary metastasis, bFGF serum levels
      were found to be significantly higher when compared to patients lacking
      progressive lung lesions (p < or = 0.0006). Of fifteen patients with bFGF levels
      lower than 14 pg/ml, six showed bone metastases at the time of sample collection
      (p < or = 0.04). Our results suggest that increased serum bFGF levels may be
      associated with a higher frequency of progressive pulmonary metastases.
      Interactions between soluble angiogenic factors and components of the
      extracellular matrix or basement membranes in remote sites of metastasis will be
      subject to further experiments.

PMID- 8572646
TI  - Review of current clinical experience with prolonged (oral) etoposide in cancer
      treatment.
AB  - Prolonged oral etoposide monotherapy is an effective treatment in patients with
      small cell lung cancer (SCLC) and refractory malignant lymphoma. It shows
      remarkable activity in relapsed or refractory breast and ovarian cancer (response
      rates up to 35% and 26%), and was also active in refractory germ cell tumours.
      Results in small numbers of patients with haematological malignancies merit
      further investigation. There is considerable pharmacokinetic variability after
      oral etoposide administration and further investigations are needed to establish
      optimal dose. Side effects (in particular leucopenia and universal alopecia)
      should not be underestimated, especially in elderly bad risk patients.

PMID- 8572649
TI  - Correlation of serum sialic acid fractions as markers for carcinoma of the
      uterine cervix.
AB  - Serum total sialic acid (TSA) and lipid-bound sialic acid (LSA) levels have
      aroused considerable interest as markers of malignancy. FSA (Free Sialic Acid)
      has not been considered as a potential tumor marker due to a lack of sensitivity
      of the methods used in the studies performed up to now. The present investigation
      determined the TSA, CLSA (Corrected Lipid Sialic Acidi) and FSA values for 20
      normal females, 10 patients with benign gynecological disease and 32 patients
      with various stages of carcinoma of the uterine cervix. Data analysis indicated
      significant (0.01 < P < 0.05) increases of TSA value only in the mean values (671
      +/- 126 micrograms mL-1) in stage II A of carcinoma of the uterine cervix when
      compared to normal controls (mean 534 +/- 102 micrograms mL-1). It showed,
      instead, significant (0.01 < P < 0.1) increases of CLSA values only in the mean
      values (6.41 +/- 1.32 micrograms mL-1) found on stage I B of carcinoma of the
      uterine cervix when compared to normal controls (mean 5.33 +/- 1.50 micrograms mL
      1). In the case of FSA significant differences were found with respect to normal
      controls (mean 0.316 +/- 0.081 micrograms mL-1) in all stages of carcinoma of the
      uterine cervix. The mean values found were 0.485 +/- 0.118 micrograms mL-1 (0.001
      < P < 0.01) in patients with stage I A, 0.666 +/- 0.176 micrograms mL-1 (P <
      0.001) in patients with stage I B and 0.572 +/- 0.164 +/- micrograms mL-1 (0.001
      < P < 0.01) in patients with stage II A. TSA and CLSA separated measurements
      appeared to be of limited value in the detection of carcinoma of the uterine
      cervix. However, results show that FSA was the most sensitive of the three
      markers tested for detecting malignancies.

PMID- 8572648
TI  - Prevalence of EBV in oral squamous cell carcinomas in young patients.
AB  - BACKGROUND: Recent studies reported a difference in the age distribution of oral
      squamous cell carcinoma (OSCC) between Black and White South Africans with OSCC
      more prevalent in Black patients under the age of 50 compared to Whites.
      MATERIALS AND METHODS: Paraffin embedded blocks of OSCC were divided into two
      groups: one with a mean age of 56.2 years and the second group all younger than
      40 years of age. A control group of 30 non-neoplastic intraoral lesions were
      selected. A standard PCR reaction was used to amplify the BAM H1 W-fragment of
      the EBV. RESULTS: EBV DNA was demonstrated in 11/45 (24%) cases from the first
      group and in 11/45 (24%) cases from the second group. EBV DNA was present in
      11/30 (37%) cases from the control group. CONCLUSIONS: This study showed that the
      prevalence of EBV in OSCC was not influenced by the age of the patient.

PMID- 8572650
TI  - D-CECaT as preoperative chemotherapy for unresectable neuroblastoma in children
      over one year of age.
AB  - The role of intensive pre- and postoperative chemotherapy in unresectable
      nonmetastatic neuroblastoma is still controversial. A preoperative regimen that
      included deferoxamine, cyclophosphamide, etoposide, carboplatin and thiotepa (D
      CECaT) was evaluated in 10 children over one year of age at diagnosis, and this
      was followed by surgery and postoperative chemotherapy. After four courses of D
      CECaT, the response rate was 9/10 with 3 complete responses, 6 partial responses
      and 1 minor response. Severe but transitory myelosuppression was the major toxic
      effect. Complete remission by combined D-CECaT chemotherapy and surgery was
      obtained in 9/10 patients, while 1 case achieved complete remission only with
      postoperative chemotherapy. All children are disease-free with a median follow-up
      of 30.5 months (range: 1+ to 50+). This intensive treatment was effective in both
      standard- and high-risk unresectable NB. However, whether a less intensive
      approach and fewer courses can also give similar results in standard-risk cases
      warrants further study.

PMID- 8572651
TI  - Small intestinal mucin antigen (SIMA); a novel tumour marker in colorectal
      cancer?
AB  - The aim of the present prospective study was to evaluate the clinical value of a
      new serum tumour marker small intestinal mucin antigen (SIMA) in the diagnosis of
      colorectal cancer. The serum SIMA values were measured in a prospective series of
      patients with colorectal cancer (n = 73) and patients with benign
      gastrointestinal disease (n = 87). SIMA values were determined using two
      different techniques. The cut-off levels (90 % specificity) determined for each
      test were 12.0 U/ml for SIMA I (Delphia), 9.8 U/ml for SIMA II (PCA-Delphia), 2.5
      ng/ml for CEA, 17 U/ml for CA 50 and 17 U/ml for CA 242. The diagnostic
      sensitivity of the SIMA I test was 0.27, of the SIMA II test it was 0.19, of the
      CEA test it was 0.63, of the CA 50 test it was 0.30 and 0.30 for the CA 242 test
      in detecting colorectal cancer. The correlation coefficients (Pearson's r) in
      colorectal cancer patients between SIMA I and SIMA II measurements were 0.99,
      0.71 between CEA and CA 50, 0.70 between CEA and CA 242 and 0.96 between CA 50
      and CA 242 measurements. The correlation coefficients in colorectal cancer
      patients between other serum markers were non-significant. All marker tests were
      entered in a multivariate analysis to find the best combination of independent
      predictors of colorectal cancer. The most important predictor of colorectal
      cancer was SIMA I. In order to calculate the contributions of tumour marker
      tests, a diagnostic score (DS) was developed. The sensitivity of the DS in
      detecting colorectal cancer was 0.33 with a specificity of 0.90 and an efficiency
      of 0.65. In conclusion, the results indicate that the diagnostic sensitivity of a
      new tumour marker SIMA is equal to CA50 and CA 242, but inferior to the
      diagnostic sensitivity of the CEA test. However, multivariate discriminant
      analysis suggests some diagnostic value for SIMA I test because of its
      independent discriminant value.

PMID- 8572652
TI  - Neo-adjuvant chemotherapy with carboplatin, 4-epiadriamycin and teniposide (CET)
      in locally advanced cancer of the cardia and the lower oesophagus: a phase II
      study.
AB  - Disappointing results after surgery alone for locally advanced adenocarcinoma of
      the cardia and the distal oesophagus (stage IIIB/IV) prompted us to combine
      surgery with neo-adjuvant chemotherapy. With a remission rate of about 70% the
      combination of etoposide, adriamycin and cisplatin (EAP) has been considered to
      be the superior treatment, but it has inherent severe toxicity. The authors
      conducted a phase II study of combined treatment with Carboplatin, 4
      Epiadriamycin and Teniposide (CET) to ameliorate this toxicity and to evaluate
      the effectivity of this regimen in patients with these unresectable tumours. A
      regimen of 4 cycles of Carboplatin 300mg/m2, 4-Epiadriamycin 80mg/m2 and
      Teniposide 100mg/m2 was administered intravenously. Treatment cycles were
      repeated every 3 weeks in patients with initially unresectable adenocarcinoma of
      the gastro-oesophageal junction proven at laparotomy and/or CT scanning. Nineteen
      patients were studied and 17 underwent a second laparotomy in an attempt to
      resect the tumour radically. Eleven patients (65%) of the re-explored group
      achieved tumour reduction, enabling resection with curative intent. Recurrences,
      however occurred in 9 patients after a median of 9.5 (4-42) months. One patient
      died postoperatively as a result of pulmonary embolism. Only one patient remained
      free of disease after 42+ months. Leucopenia and thrombocytopenia of WHO grade 23
      occurred in 58% and 37% of the patients, respectively. This regimen appears to be
      effective in patients with locally advanced adenocarcinoma of the cardia and the
      distal oesophagus. Although it can be used in an outpatient setting, the overall
      toxicity is relatively high and the results are comparable with other less toxic
      regimens.

PMID- 8572653
TI  - Immunostimulation by propionibacteria--effects on immune status and
      antineoplastic treatment.
AB  - Experimental studies were performed to investigate further the effects of
      immunotherapy with Propionibacterium avidum KP-40 on thymocyte proliferation,
      maturation and emigration in BALB/c-mice. Thymus weight and thymocyte counts,
      especially cells presenting the immature or cytotoxic/suppressor phenotype were
      significantly increased. Due to enhanced emigration, peripheral blood lymphocyte
      and monocyte counts as well as expression of activation markers were
      significantly upregulated. The antimetastatic effect of Propionibacterium avidum
      KP-40 was demonstrated in BALB/c-mice, where RAW 117-H10 lymphosarcoma liver
      colonization was significantly reduced after immunostimulation. Clinical
      investigations proved that surgical treatment of colorectal carcinoma induced an
      evident decrease of peripheral blood lymphocytes as compared with preoperative
      counts. However, single preoperative Propionibacterium avidum KP-40
      administration induced a considerable increase of peripheral white blood cell
      counts, especially lymphocytes. Clinical effects of preoperative
      immunostimulation by Propionibacterium granulosum KP-45 were investigated in a
      prospective randomized trial in colorectal carcinoma patients. Positive effects
      on survival time, local tumor recurrence and distant metastasis could be
      demonstrated in stages I and II, whereas no advantage of immunotherapy was found
      in advanced stages III and IV. A recent prospective randomized clinical trial was
      initiated on the quality of life of colorectal carcinoma patients. Three months
      after surgical treatment negative effects could not be determined after
      immunotherapy. Quality of life even proved to be better in patients with
      abdominoperineal resection as compared to non Propionibacterium avidum KP-40
      treated control patients.

PMID- 8572654
TI  - Familial hemiplegic migraine, nystagmus, and cerebellar atrophy.
AB  - Familial hemiplegic migraine (FHM) is an autosomal dominant disorder
      characterized by transient hemiplegia during the aura phase of a migraine attack.
      Nystagmus has been reported in individuals affected with this disorder, but the
      origin of the ocular motility findings is unknown. A three-generation family with
      FHM is described and clinical histories are outlined. Ocular motility evaluations
      were performed on 7 family members, 5 with a history of hemiplegic migraine and 2
      without history of migraine. All affected family members had abnormal eye
      movements consistent with vestibulocerebellar dysfunction. Magnetic resonance
      imaging scans in affected family members revealed cerebellar vermian atrophy. DNA
      linkage analysis revealed a common marker in all the affected family members on
      chromosome 19. We suggest that the hemiplegic migraine attacks and the cerebellar
      degeneration are linked genetically and that the eye movements are not the
      ischemic sequelae of recurrent migraine. Strikingly similar ocular motility
      findings and cerebellar degeneration are reported in both FHM and a genetically
      related disorder, hereditary paroxysmal cerebellar ataxia (HPCA). The
      significance of these similarities is discussed along with a proposed
      pathophysiology for FHM.

PMID- 8572656
TI  - Nerve growth factor protects the neonatal brain against hypoxic-ischemic injury.
AB  - Nerve growth factor (NGF) has been shown to protect specific neurons that express
      its signaling receptor, trkA, from a variety of insults. There are some data, in
      particular in the developing brain, indicating that NGF has neuroprotective
      actions that extend beyond cells expressing trkA. In this study, we asked whether
      NGF would protect against brain injury in a neonatal model of hypoxia-ischemia.
      Postnatal day (PD) 7 rat pups received a right carotid ligation and were then
      exposed to hypoxic conditions. Prior to carotid ligation and 48 hours later, pups
      received an intracerebroventricular injection of NGF or denatured NGF dissolved
      in vehicle or vehicle alone. Brains were then assessed at PD21. In vehicle- and
      denatured NGF-treated animals, there was significant damage (30-40% volume loss)
      to both the striatum and cortex ipsilateral to the carotid ligation. In contrast,
      little damage (10% volume loss) was observed in most NGF-treated animals. NGF
      injection studies revealed that NGF stimulated tyrosine phosphorylation of trkA
      in multiple brain regions. These results show that NGF appears globally
      neuroprotective to the developing brain in a neonatal model of hypoxia-ischemia
      and that there may be novel mechanisms in vivo through which NGF exerts its
      protective actions.

PMID- 8572655
TI  - Proton magnetic resonance spectroscopy in children with temporal lobe epilepsy.
AB  - We performed proton magnetic resonance spectroscopy of the mesial temporal
      regions in 20 children with intractable temporal lobe epilepsy and compared
      results with those from 13 normal subjects. Abnormalities of the ratio of N
      acetylaspartate to choline plus creatine (NAA/[Cho+Cr]) were seen in 15 patients
      (75%). The ratio NAA/(Cho+Cr) was correctly lateralizing in 55% and incorrectly
      lateralizing in none. Bilateral abnormalities were seen in 45%. Overall there was
      a unilateral decrease in N-acetylaspartate on the side ipsilateral to the seizure
      focus (mean 19% decrease vs normals, with 5% decrease on the contralateral side),
      suggesting neuronal loss or dysfunction. There was also a bilateral increase in
      creatine and choline (mean 18%), consistent with reactive astrocytosis. We
      conclude that proton magnetic resonance spectroscopy can contribute to
      lateralization of the seizure focus, and by detection of bilateral abnormalities,
      can contribute to the understanding of the underlying pathophysiology in temporal
      lobe epilepsy.

PMID- 8572657
TI  - Interleukin-1 receptor antagonist suppresses neurotrophin response in injured rat
      brain.
AB  - Traumatic brain injury (TBI) induces astrocytic and microglial activation and
      proliferation and augmented production of the cytokine interleukin-1 beta (IL-1
      beta) and nerve growth factor (NGF). The increase in NGF temporally follows the
      increase in IL-1 beta, suggesting that the IL-1 beta up-regulation after trauma
      directly induces the increase in NGF. We examined the effect of IL-1 receptor
      antagonist protein (IL-1ra) on microglial proliferation and NGF production in rat
      cortex, following two different models of TBI. Rabbit fibroblasts infected with a
      retroviral vector containing the human IL-1ra gene were implanted into the wound
      cavity immediately following a cortical stab wound or 6 hours after a weight drop
      induced trauma. Both microglial proliferation and NGF up-regulation were
      decreased significantly in animals receiving IL-1ra-expressing cells compared
      with animals receiving naive (untransfected) fibroblasts. These data demonstrate
      that the increase in NGF after central nervous system trauma is directly mediated
      through IL-1 beta and that blocking IL-1 beta following brain injury leads to
      suppression of an NGF-mediated reparative response. Such blockade of
      inflammation, however, may prove to be of significant therapeutic benefit in
      human brain injury and other inflammatory states.

PMID- 8572658
TI  - SOD1 mutation is associated with accumulation of neurofilaments in amyotrophic
      lateral sclerosis.
AB  - Mutations in the Cu/Zn superoxide dismutase (SOD1) gene are found in 15 to 20% of
      patients with familial amyotrophic lateral sclerosis (FALS). Increased levels of
      neurofilament subunits in transgenic mouse models of ALS also suggests a key role
      for these proteins in the pathogenesis of the disease. We report the coexistence
      of an Ile113-->Thr substitution in exon 4 of the SOD1 gene and marked
      neurofilamentous pathology in the same FALS patient. These observations suggest
      that two mechanisms, SOD1-induced toxicity and neurofilament disruption, are
      acting together.

PMID- 8572659
TI  - Relationship between trinucleotide repeats and neuropathological changes in
      Huntington's disease.
AB  - The discovery of the Huntington's disease (HD) gene has provided the impetus to
      determine the association between the triplet repeat sequences and clinical
      manifestations of the disease. The present study is directed toward determining
      the relationship between the triplet repeat sequences and severity of the
      neurodegenerative process. Nineteen HD postmortem cases were evaluated for
      neuropathological changes as well as for the number of trinucleotide repeat
      sequences, each in a blinded fashion. Each case was assigned a gross grade
      according to the scale of Vonsattel and colleagues (1985); neuronal counts were
      then performed on both the caudate and the putamen. For 7 of the postmortem
      cases, blood had been collected prior to death and was analyzed for the HD gene.
      For the 12 remaining cases for which blood was unavailable, DNA from the frontal
      neocortex and striatum was extracted from frozen or formalin-fixed paraffinized
      tissue and subsequently analyzed for the HD gene. When correlation was made for
      age at death, greater numbers of trinucleotide repeats were associated with
      greater neuronal loss, in both the caudate (r = 0.9641, p < 0.001) and the
      putamen (r = 0.9652, p < 0.001). When correction was made for disease duration,
      the correlation was again significant, for both the caudate (r = 0.6396, p <
      0.01) and the putamen (r = 0.6710, p < 0.001). This suggests that in HD, longer
      trinucleotide repeat length is associated with a faster rate of deterioration and
      greater pathological severity. A comparison of trinucleotide repeat length in
      different brain regions in 4 of the HD postmortem cases associated with greater
      numbers of repeats consistently demonstrated fewer repeats in the cerebellum than
      in the frontal cortex, striatum or blood.

PMID- 8572660
TI  - Intravenous gamma-globulin inhibits binding of anti-GM1 to its target antigen.
AB  - In this study, we preincubated the sera of 3 patients with neuropathies
      associated with elevated titers of IgM anti-GM1 antibodies, with increasing
      concentrations of intravenous Ig (IVIg) and assayed the inhibitory effect of this
      mixture on antibody binding to immobilized GM1 by an enzyme-linked immunosorbent
      assay. Pharmacologic concentrations of IVIg, ranging from 0.1 microgram/ml to 100
      mg/ml, inhibited anti-GM1 binding to its target antigen from 26 +/- 3 to 71 +/-
      7%, respectively, in a dose-dependent manner. A similar inhibition of binding was
      also observed with IVIg F(ab')2 fragments. These findings provide a possible
      mechanism for the clinical efficacy of IVIg in motor neuropathies.

PMID- 8572661
TI  - Sporadic inclusion body myositis: counts of different types of abnormal fibers.
AB  - Invasion of nonnecrotic muscle fibers by cytotoxic T cells, accumulation of
      congophilic amyloid inclusions in muscle fibers, and fiber necrosis are
      consistent histologic findings in sporadic inclusion body myositis (IBM). To
      evaluate the relative significance of these alterations, we quantitatively
      analyzed the frequency of these abnormalities in 31 electron microscopy proven
      cases of IBM (20 untreated and 11 immunosuppressed). Nonnecrotic muscle fibers
      invaded by T cells were severalfold more frequent than fibers displaying the
      other pathologic alterations. Comparison of muscle samples from treated and
      untreated patients revealed no significant differences in the respective
      frequencies of the three species of abnormal fibers. Moreover, there was no
      correlation of the frequency of any abnormality either with disease duration or
      length of treatment. The much higher frequency of the invaded than Congo red
      positive fibers points to the importance of an immune-mediated mechanism in the
      disease; but the basic cause of the disease remains undefined.

PMID- 8572662
TI  - Pathology of the motor-sensory axonal Guillain-Barre syndrome.
AB  - The concept of a severe motor-sensory neuropathy of acute onset caused by an
      immune attack on the axon ("axonal" Guillain-Barre syndrome) has been advanced
      primarily based on electrodiagnostic and limited pathological data, but remains
      controversial. At autopsy some cases demonstrate unusually severe inflammatory
      demyelinating neuropathy. There are conflicting data about whether antecedent
      Campylobacter jejuni infection is associated with "axonal" Guillain-Barre
      syndrome. We report 4 individuals from Hebei Province, China, who died 7, 7, 18,
      and 60 days after onset of a syndrome diagnosed clinically as Guillain-Barre
      syndrome. High titers of antibodies recognizing C. jejuni, consistent with recent
      infection, were found in the 2 patients tested. At autopsy the 3 with early
      disease had ongoing wallerian-like degeneration of fibers in the ventral and
      dorsal roots and in the peripheral nerves, with only minimal demyelination or
      lymphocytic infiltration. All 3 had numerous macrophages in the periaxonal space
      of myelinated internodes, and rare intraaxonal macrophages as well. Examination
      of the patient having the syndrome for 60 days confirmed the extensive loss of
      large fibers in the spinal roots and nerves, and the paucity of demyelination and
      remyelination. These observations confirm predictions that some patients with
      severe motor-sensory Guillain-Barre syndrome, as defined clinically, have
      predominantly axonal lesions of both motor and sensory fibers, even in the early
      stages of the disease, and that axonal Guillain-Barre syndrome can follow C.
      jejuni infection. The pathology supports the possibility that such cases of motor
      sensory axonal Guillain-Barre syndrome represent the most severe end of a
      spectrum of immune attack directed toward epitopes on the axon.

PMID- 8572663
TI  - Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP
      subjects not requiring levodopa. Parkinson Study Group.
AB  - In the controlled trial Deprenyl and Tocopherol Antioxidative Therapy of
      Parkinsonism (DATATOP), 310 of the 800 enrolled subjects did not reach the
      primary end point of disability requiring levodopa therapy during 21 +/- 4 (mean
      +/- SD) months of observation or need early initiation of deprenyl (selegiline)
      during a 2-month withdrawal of experimental treatments. While maintaining the
      blindness of their original deprenyl and tocopherol treatment assignments, these
      310 subjects were administered deprenyl 10 mg/day (open label) and were monitored
      systematically at 1- to 3-month intervals for up to 18 months (12 +/- 5 mo).
      During this extended trial, the 189 subjects who had been assigned originally to
      active deprenyl tended to reach the end point of disability faster than the 121
      subjects who had not been assigned originally to deprenyl (hazard ratio, 1.43;
      95% CI, 0.98, 2.09; p = 0.065). However, the differential rates of reaching the
      end point may have been due in part to the more severe baseline impairment of
      deprenyl-assigned subjects, who benefited originally from deprenyl but who were
      more likely to require levodopa during this extended period of observation. Prior
      treatment with deprenyl did not lead to superior survival with respect to the end
      point of disability requiring levodopa, suggesting that the initial advantages of
      deprenyl were not sustained.

PMID- 8572665
TI  - The axon in Guillain-Barre syndrome: immune target or innocent bystander?

PMID- 8572664
TI  - Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP
      patients requiring levodopa. Parkinson Study Group.
AB  - The Deprenyl and Tocopherol Antioxidant Therapy of Parkinsonism (DATATOP) trial
      was designed to test outcomes from treatment with 10 mg of deprenyl and/or 2,000
      mg of tocopherol/day in 800 untreated patients with Parkinson's disease. The need
      of subjects for symptomatic treatment with levodopa and the conversion of all
      subjects to open-label deprenyl made it possible to study the long-term effect of
      early deprenyl and tocopherol treatment on the later development of levodopa
      associated side effects. The rate of developing these side effects did not differ
      among the original treatment groups (early versus late deprenyl and tocopherol
      versus nontocopherol). About 50% of subjects developed "wearing off," 30%
      dyskinesias, and 25% "freezing" in each group. At the end of the study, the
      groups were similarly disabled on the Hoehn-Yahr, Schwab-England, and Unified
      Parkinson's Disease Rating scales and took similar amounts of levodopa. Young
      subjects were more likely to develop wearing off, women to develop dyskinesias,
      and older subjects with rapidly progressive disease to develop freezing. We
      conclude that prior treatment with deprenyl or tocopherol did not reduce the
      occurrence of subsequent levodopa-associated adverse effects in this population.

PMID- 8572666
TI  - Intravenous antigen administration as a therapy for autoimmune demyelinating
      disease.
AB  - Experimental allergic encephalomyelitis is a prototypic autoimmune disease
      characterized by central nervous system inflammation and demyelination.
      Previously, we demonstrated that intravenous administration of high doses of
      myelin basic protein abrogated the clinical and pathological signs of
      experimental allergic encephalomyelitis by causing the deletion of
      encephalitogenic, CD4+, myelin basic protein-specific T cells through antigen
      induced programmed cell death. In the present study, we further characterized the
      ability of intravenous antigen administration to attenuate an immune response by
      myelin basic protein-reactive encephalitogenic T cells. We demonstrated that
      multiple injections of myelin basic protein are required to achieve a therapeutic
      response, and that this form of therapy is effective even after prolonged chronic
      disease. These studies showed that although interleukin-2-stimulated cell cycling
      is an important factor leading to T-cell death, the administration of exogenous
      interleukin-2 with antigen can result in the aggravation of clinical disease
      compared to administration of antigen alone. More importantly, administration of
      myelin basic protein alone without interleukin-2 was sufficient to reduce
      autoreactive T cells and clinical disease in experimental autoimmune
      encephalomyelitis. Our experiments support the rationale for antigen-specific
      therapy aimed at inducing the programmed death of autoreactive T cells in
      autoimmune diseases, potentially including the human demyelinating disease
      multiple sclerosis.

PMID- 8572667
TI  - Enhanced expression of microtubule-associated protein 2 in large neurons of
      cortical dysplasia.
AB  - To evaluate neuronal cytoarchitectural changes in cortical dysplasia, we examined
      microtubule-associated protein 2 (MAP2) expression in surgically resected
      specimens obtained from 20 patients (age range, 3 months to 10 years) treated for
      intractable epilepsy. Large neurons were investigated in the specimens from all
      patients and showed significantly strong immunoreactivity with antibodies against
      MAP2 in the perikaryon and proximal portion of their processes. In situ
      hybridization with MAP2 antitense riboprobe showed increased hybridization signal
      intensities in the large neurons, which correlated with the pattern of
      immunoreactivity for MAP2. We conclude that MAP2 is strongly expressed in the
      large neurons in cortical dysplasia. The results of preliminary immunoblotting in
      1 patient with focal cortical dysplasia showed that the low-molecular-weight form
      of MAP2 (MAP2c) was strongly expressed in the dysplastic cortex, suggesting that
      MAP2c may be a major component contributing to the increased expression of MAP2
      in the large neurons of cortical dysplasia. Since it has been suggested that MAP2
      plays a crucial role in the branching and remodeling of neuronal processes,
      increased expression of MAP2 may reflect activated plasticity of the large
      neurons in cortical dysplasia.

PMID- 8572668
TI  - Guidelines for the use of magnetic resonance techniques in monitoring the
      treatment of multiple sclerosis. US National MS Society Task Force.
AB  - Because of the major difficulties in measuring clinical end points in multiple
      sclerosis (MS) treatment trials, there has been much enthusiasm for using
      magnetic resonance imaging (MRI) findings as an alternative outcome. To provide
      international consensus guidelines for the use of MRI in MS clinical trials, a
      task force of the US National MS Society was convened. The recommendations of the
      task force are presented in this review. Given the high sensitivity for detecting
      pathological activity in relapsing-remitting and secondary progressive MS,
      monthly T2-weighted and gadolinium-enhanced brain MRI is an excellent tool for
      short-term exploratory trials of new agents where it serves as the primary end
      point; in particular, failure to demonstrate a reduction in lesion activity
      avoids the time, cost, and risks of a larger clinical end point study. However,
      conventional MRI findings have a limited correlation with disability in
      established MS. The primary end point of a definitive trial should therefore be
      clinical, although serial MRI at 6- to 12-month intervals is a useful secondary
      end point in providing an index of pathological progression. In trials of
      patients presenting with clinically isolated syndromes suggestive of MS, MRI
      findings can be used in the entry criteria, and as a secondary outcome measure,
      but conversion to clinically definite MS should be the primary outcome. The
      pathological substrates of irreversible disability are demyelination and axonal
      loss. Putative magnetic resonance markers for these processes include decreased N
      acetylaspartate on proton magnetic resonance spectroscopy, decreased
      magnetization transfer ratios, hypointensity on T1-weighted images, and loss of
      short T2 water fractions, some of which relate more closely to disability than
      conventional MRI findings. Further technical developments should lead to more
      accurate quantitation, greater pathological specificity, and stronger clinical
      correlations.

PMID- 8572669
TI  - Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer's
      disease.
AB  - Inheritance of the apolipoprotein E (apoE) epsilon 4 allele is associated with a
      high likelihood of developing Alzheimer's disease (AD). The pathophysiologic
      basis of this genetic influence is unknown. We reasoned that understanding the
      influence of apoE epsilon 4 on the clinical course and neuropathological features
      of AD may provide tests of potential mechanisms. We carried out a prospective
      longitudinal study to compare the age of onset, duration, and rate of progression
      of 359 AD patients to apoE genotype. Thirty-one of the individuals who died
      during the study were available for quantitative neuropathological evaluation.
      Statistically unbiased stereological counts of neurofibrillary tangles (NFTs) and
      A beta deposits were assessed in a high-order association cortex, the superior
      temporal sulcus. Analysis of clinical parameters compared with apoE genotype
      showed that the epsilon 4 allele is associated with an earlier age of onset but
      no change in rate of progression of dementia. Quantitative neuropathological
      assessment revealed that NFTs were strongly associated with clinical measures of
      dementia duration and severity but not with apoE genotype. A beta deposition, by
      contrast, was not related to clinical features but was elevated in association
      with apoE epsilon 4. These results indicate that apoE epsilon 4 is associated
      with selective clinical and neuropathological features of AD and support
      hypotheses that focus on an influence of apoE epsilon 4 on amyloid deposition.

PMID- 8572670
TI  - Proton magnetic resonance spectroscopic imaging in patients with cerebellar
      degeneration.
AB  - Using proton magnetic resonance spectroscopic imaging, we studied the cerebellum
      of 9 patients with cerebellar degeneration and of 9 age-matched normal control
      subjects. This technique permits the simultaneous measurement of N
      acetylaspartate, choline-containing compounds, creatine/phosphocreatine, and
      lactate signal intensities from four 15-mm slices divided into 0.84-ml single
      volume elements. Because patients with cerebellar degeneration often show
      substantial atrophy on magnetic resonance imaging (MRI), we specifically chose to
      analyze the spectroscopic signals only from tissue that did not have an atrophic
      appearance on the MRI. The spectroscopic findings showed a significant reduction
      of N-acetylaspartate in all parts of the cerebellum, a significant correlation
      with MRI scores of cerebellar atrophy, and a significant correlation with
      clinical rating scores of cerebellar disturbance. Our method of analysis suggests
      the presence of a neurodegenerative process in cerebellar areas that do not
      appear to be atrophic on the MRI. Some limitations of proton magnetic resonance
      spectroscopic imaging in the present study were related to the partial field
      inhomogeneity characteristics of the posterior fossa, the anatomical location of
      the cerebellum, and the particularly severe cerebellar atrophy in some of the
      patients.

PMID- 8572671
TI  - Strength in Parkinson's disease: relationship to rate of force generation and
      clinical status.
AB  - Maximum elbow flexor and extensor muscle strength was measured in 9 patients with
      Parkinson's disease on and off antiparkinsonian medication. In addition, the rate
      of force generation, the rate of actively returning force to resting levels, and
      passive release of force "relaxation" were measured in submaximal contractions.
      The measures of strength and contraction time were correlated with changes in
      clinical status as measured by the Unified Parkinson's Disease Rating Scale. When
      patients were off medication, their reduction in strength was significantly
      greater in extension than flexion. The reduction in flexion strength did not
      reach statistical significance. The extensor weakness was primarily due to
      decreased tonic activation of the extensor muscles and not to muscle
      coactivation. Muscle relaxation time was much more prolonged than was force
      generation time or active force return time. The increase in relaxation time and
      the decrease in extensor strength both correlated with changes in clinical
      status. Finally, changes in extensor torque correlated with the time to actively
      return force, suggesting that reduced strength is related to a reduced ability to
      generate rapid contractions in some patients with Parkinson's disease. These
      results suggest that there is an asymmetric distribution of muscle weakness in
      Parkinson's disease and that selected measures of muscle strength and muscle
      relaxation correlate with changes in clinical status.

PMID- 8572672
TI  - Dietary lipids and antioxidants in Parkinson's disease: a population-based, case
      control study.
AB  - Oxidative stress plays an important role in the pathogenesis of Parkinson's
      disease (PD). In a population-based, case-control study we examined whether
      dietary intake of antioxidants and other oxidative compounds was associated with
      PD. Dietary intake was assessed by a semiquantitative food-frequency
      questionnaire in 110 PD case patients and 287 control subjects. A higher caloric
      intake was observed in patients with PD and did not vary with increasing duration
      of symptoms. Energy-adjusted fat intake was significantly higher among patients
      with PD than control subjects (p for trend = 0.007). Intake of protein (p for
      trend = 0.17) and carbohydrates (p for trend = 0.46) did not differ in patients
      and control subjects. Analyses of the primary sources of fat indicated that
      increasing intake of animal fats were strongly related to PD (odds ratio, 5.3;
      95% confidence interval, 1.8-15.5; p for trend = 0.001). No significant
      differences were observed for intake of vitamins with antioxidant activity. An
      increase in the consumption of animal fats among patients with PD is consistent
      with the hypothesis that oxidative stress and lipid peroxidation are important in
      the pathogenesis of this disease. No effect of vitamins with antioxidant
      activity, either from food or supplements, was observed.

PMID- 8572673
TI  - The effect of gabapentin on brain gamma-aminobutyric acid in patients with
      epilepsy.
AB  - Gabapentin has come into clinical use as adjunctive therapy in the treatment of
      epilepsy. Designed to mimic gamma-aminobutyric acid (GABA), its mechanism of
      action remains elusive. In vivo measurements of GABA in human brain were made
      using 1H magnetic resonance spectroscopy. We used a 2.1-T magnetic resonance
      imager-spectrometer and an 8-cm surface coil to measure a 13.5-cm3 volume in the
      occipital cortex. GABA levels were measured in 14 patients enrolled in an open
      lbel trial of gabapentin. GABA was elevated in patients taking gabapentin
      compared with 14 complex partial epilepsy patients, matched for antiepileptic
      drug treatment. Brain GABA levels appeared to be higher in patients taking high
      dose gabapentin (3,300-3,600 mg/day) than in those taking standard doses (1,200
      2,400 mg/day). Gabapentin appears to increase human brain GABA levels.

PMID- 8572674
TI  - The relationship between kinetics of substrate-limited transitions and steady
      state growth in continuous cultures of Aquaspirillum autotrophicum limited by
      pyruvate.
AB  - Heterotrophic growth at steady state and during transient states caused by the
      sudden change of the concentration of the limiting factor in the feed medium was
      investigated experimentally for continuous cultures of Aquaspirillum
      autotrophicum limited by pyruvate. A model for describing the growth at steady
      state was selected from three unstructured models after statistical tests of the
      data. This model postulates that the growth yield increases linearly with the
      growth rate. Growth during transitions where the substrate remained limiting at
      all times was fitted with first-order kinetics. Theoretical predictions of these
      kinetics were derived from the unstructured models used to describe steady state.
      The predicted rate coefficients of the transients were compared to the
      experimental coefficients. It appeared that the model which best described steady
      state growth also provided the best predictions for growth during the transient
      state. It is a widespread opinion that unstructured models are adequate to
      describe growth under steady-state conditions but not to predict transitions in
      continuous culture. However, for the particular case studied here, no higher
      degree of complexity was required to describe transitions, provided the growth of
      the culture was always limited by the substrate.

PMID- 8572675
TI  - Occurrence of Salmonella in cold-blooded animals in Gran Canaria, Canary Islands,
      Spain.
AB  - The occurrence of Salmonella in endemic and subendemic species of lizard and frog
      of Gran Canaria, Gallotia stehlini and Rana perezi, as well as captive reptiles
      from other regions of the world was investigated. The occurrence of Salmonella
      was statistically higher in endemic and subendemic species than in captive
      animals (p < 0.001). Seventy strains of Salmonella were isolated. S. berta and S.
      gran canaria were the most frequently isolated serotypes. The study of Salmonella
      in gall-bladder contents showed a high parasitation (85%), being higher in
      Gallotia stehlini (100%) than in Rana perezi (60%). None of the isolated
      salmonellae were resistant to tested antibiotics.

PMID- 8572677
TI  - Hexavalent-chromium reduction by a chromate-resistant Bacillus sp. strain.
AB  - Bacillus strain QC1-2, isolated from a chromium-polluted zone, was selected by
      its high ability to both tolerate and reduce hexavalent chromium [Cr(VI)] to less
      toxic trivalent chromium [Cr(III)]. Cell suspensions of strain QC1-2 rapidly
      reduced Cr(VI), in both aerobic and anaerobic conditions, to Cr(III) which
      remained in the supernatant. Cr(VI) reduction was dependent on the addition of
      glucose but sulfate, an inhibitor of chromate transport, had no effect. Studies
      with permeabilized cells and cell extracts showed that the Cr(VI) reductase of
      strain QC1-2 is a soluble NADH-dependent enzyme.

PMID- 8572676
TI  - Preliminary characterization of the material released to the culture medium by
      Candida albicans yeast and mycelial cells.
AB  - Culture filtrate concentrates were obtained from Candida albicans yeast and
      mycelial cells grown in the presence of 14C-protein hydrolysate for radioactive
      labeling of cellular polypeptides. Both growth forms released to the medium minor
      but significant amounts of proteinaceous materials. The analysis of culture
      filtrate concentrates by means of SDS-polyacrylamide gel electrophoresis and
      fluorography revealed a similar and complex electrophoretic pattern, though some
      qualitative and quantitative differences between samples obtained from yeast and
      mycelial cells were observed. Materials released, mostly composed of
      mannoproteins as shown by their affinity towards concanavalin A, presented (i)
      cross-reactivity (by Western immunoblotting and ELISA) against polyclonal
      antisera to genuine cell wall components (among them the 58-kilodalton fibrinogen
      binding mannoprotein) and (ii) high affinity for polystyrene-latex microbeads.
      Results presented suggest a possible common identity for the molecules shed to
      the medium and the cell wall protein and mannoprotein constituents.

PMID- 8572678
TI  - Purification and properties of urease from Sporobolomyces roseus.
AB  - Urease (EC 3.5.1.5) catalyses the hydrolysis of urea to ammonia and carbon
      dioxide. The enzyme from Sporobolomyces roseus was enriched 780-fold and purified
      to apparent homogeneity using heat treatment, ion exchange chromatography on Q
      Sepharose fast flow, hydrophobic interaction chromatography on Phenyl-Sepharose,
      size exclusion chromatography on Sephacryl S 300 HR, and ion exchange
      chromatography on MonoQ. Analysis of the purified enzyme by SDS-PAGE demonstrated
      the presence of subunits with a molecular weight of 90 (+/- 4) kDa. The M(r) of
      the native enzyme was estimated by size exclusion chromatography to be 340 (+/-
      30) kDa, suggesting a tetrameric structure different from other ureases isolated
      so far from both prokaryotes and eukaryotes. The enzyme was heat-stable, showing
      no loss of activity after incubation at 70 degrees C for 15 min. The highest
      urease activities were observed after growth on media containing urea as the sole
      source of nitrogen.

PMID- 8572679
TI  - Temperature-dependent dimorphism of the yeast Arxula adeninivorans Ls3.
AB  - Arxula adeninivorans Ls3 is described as an ascomycetous, arthroconidial,
      anamorphic, xerotolerant yeast, which was selected from wood hydrolysates in
      Siberia. By using minimal salt medium or yeast-extract-peptone-medium with
      glucose or maltose as carbon source it was shown that this yeast is able to grow
      at up to 48 degrees C. Increasing temperatures induce changes in morphology from
      the yeast phase to mycelia depending on an altered programme of gene expression.
      This dimorphism is an environmentally conditioned (reversible) event and the
      mycelia can be induced at a cultivation temperature of 45 degrees C. Depending on
      the morphology of strain Ls3 (yeast phase or mycelia) the secretion behaviour as
      well as the spectrum of polypeptides accumulated in the culture medium changed.
      The activities of the accumulated extracellular enzymes glucoamylase and
      invertase were 2 to 3 times higher in cultures grown at 45 degrees C than in
      those grown at 30 degrees C. While the level of the glucoamylase protein secreted
      from mycelia between 45 and 70 hours did not change, biochemical activity
      decreased after a cultivation time of 43 hours. It was shown that this effect
      depended on both the catabolic repression of the glucoamylase by glucose and the
      thermal inactivation of this enzyme in media without or with low concentrations
      of starch or maltose.

PMID- 8572680
TI  - Chromosome-encoded inducible copper resistance in Pseudomonas strains.
AB  - Nine Pseudomonas strains were selected by their high copper tolerance from a
      population of bacteria isolated from heavy-metal polluted zones. Copper
      resistance (Cu(r)) was inducible by previous exposure of cultures to
      subinhibitory amounts of copper sulfate. All nine strains possessed large
      plasmids, but transformation and curing results suggest that Cu(r) is conferred
      by chromosomal genes. Plasmid-less Pseudomonas aeruginosa PAO-derived strains
      showed the same level of Cu(r) as environmental isolates and their resistance to
      copper was also inducible. Total DNA from the environmental Pseudomonas, as well
      as from P. aeruginosa PAO strains, showed homology to a Cu(r) P. syringae cop
      probe at low-stringency conditions but failed to hybridize at high-stringency
      conditions.

PMID- 8572681
TI  - High molecular weight precursors of glucans in Saccharomyces cerevisiae.
AB  - Nascent beta-1,3 glucan synthesized by mixed membrane fractions from
      Saccharomyces cerevisiae was solubilized by extraction with hot SDS or urea.
      Nature of the material was analyzed by electrophoresis and gel filtration. As
      determined by gel filtration, Mr of synthesized glucans exceeded 1,500 kDa, but
      was below 20,000 kDa. This nascent material served as an acceptor for further
      glucose transfer reactions, giving rise to glucan molecules over 20,000 kDa. It
      is suggested that the high Mr precursor components represent protein-bound glucan
      molecules in transit to the cell surface.

PMID- 8572682
TI  - Bacteriolytic activities of the free-living soil amoebae, Acanthamoeba
      castellanii, Acanthamoeba polyphaga and Hartmannella vermiformis.
AB  - Bacteriolytic activities of axenically grown free-living soil amoebae
      Acanthamoeba castellanii, Acanthamoeba polyphaga and Hartmannella vermiformis
      towards various Gram-positive and Gram-negative bacteria were determined. A
      spectrophotometric assay revealed that the specific bacteriolytic activities of
      both Acanthamoeba species were higher as those of the three Hartmannella strains.
      Bacillus megaterium, Bacillus subtilis, Chromatium vinosum, Micrococcus luteus
      and Pseudomonas fluorescens were more easily lysed than the other bacteria
      tested. Agrobacterium tumefaciens, Klebsiella aerogenes and Serratia marcescens
      were hardly affected at all by the amoebal bacteriolytic activities. Among the
      Gram-negative bacteria we observed differences in lysis sensitivity while the
      Gram-positive bacteria tested were sensitive to lysis. Isoelectric focusing (IEF)
      gel-electrophoresis in the pH range 3-10 was performed to separate the
      bacteriolytic isoenzymes of amoebae. Bacteriolytic patterns were shown by using
      an activity assay in which lysis bands were formed in the agar/bacteria gel
      overlay. The activity assay revealed remarkable differences in typical banding
      patterns for bacteriolytic activities among amoebae. Distinct differences between
      typical pI points of bacteriolytic activities in Acanthamoeba and Hartmannella
      were shown. Bacteriolytic activities of Hartmannella were more pronounced and
      observed in the isoelectric points (pI) range of 4.0-9.3 while for Acanthamoeba
      the range was pI 4.5-8.9.

PMID- 8572683
TI  - Allocation of random amplified polymorphic DNA markers and enzyme activities to
      Aspergillus nidulans and Aspergillus tetrazonus chromosomes.
AB  - Chromosome-substituted haploid segregants of an A. nidulans x A. tetrazonus
      somatic hybrid were used to allocate several random amplified polymorphic DNA and
      isoenzyme markers to parental chromosomes. Twenty-six amplified DNA fragments,
      and nine isoenzyme activities, including lactate dehydrogenase, superoxide
      dismutase, and arylesterase isoenzymes were assigned to chromosomes. Chromosomes
      specific markers were found for each A. nidulans and A. tetrazonus chromosome.
      These markers could be used to saturate the genetic map of A. nidulans. The
      formation of two secondary metabolites was also assigned to chromosomes III and
      VIII. Attempts were made to allocate extracellular enzyme activities to parental
      chromosomes, mostly without success, possibly because multiple enzyme forms
      located on different chromosomes could be responsible for the production of an
      enzyme activity.

PMID- 8572684
TI  - Resolution of batch variations in pyrolysis mass spectrometry of bacteria by the
      use of artificial neural network analysis.
AB  - A simple, but stringent, three group model of bacterial interstrain identity (two
      cultures of the same strain of Escherichia coli) and difference (a culture of a
      serologically distinct strain) was used in multiple serial weekly subcultures for
      five weeks to demonstrate the effect of both growth-related (phenotypic) and
      machine-related variation on pyrolysis mass spectra. An aliquot of serum from a
      single sample was included in each pyrolysis batch to distinguish machine drift
      from culture drift. Conventional principal component (PC) canonical variate (CV)
      analysis was successful within each pyrolysis batch but the variations between
      batches precluded the use of data from more than one batch in successful PCCV
      analysis. In contrast, artificial neural networks (ANNs) trained with data from
      one batch could be successfully used to identify groups in data from non
      contemporaneous pyrolysis batches. Although the ANN method will require
      validation in more complex settings than this simple model, it is a promising
      approach to the problem of batch constraint in pyrolysis mass spectrometry.

PMID- 8572685
TI  - Production and characterization of monoclonal antibodies against the O-5 antigen
      of Salmonella typhimurium lipopolysaccharide.
AB  - Three murine monoclonal antibodies (MAbs) were produced by fusion of P3X63
      Ag8.653 myeloma cells and splenocytes of a mouse immunized with heat-attenuated
      (20 min, 80 degrees C) Salmonella typhimurium cells. MAbs 5A5 and 5B2 were of the
      immunoglobulin M (IgM) class, while MAb 4A8 was IgG2a. All possessed the kappa
      light chains. The MAbs were specific to the lipopolysaccharide (LPS) O-5 antigen
      of Salmonella B serogroup, as determined by electrophoresis followed by
      immunoblotting. All MAbs recognized the same epitope, as determined by an
      additive enzyme-linked immunosorbent assay (ELISA), although IgM MAbs exhibited
      higher avidity than the IgG MAb. ELISA analyses revealed that all three MAbs
      reacted with S. typhimurium (LPS O:1, 4, 5, and 12) while failing to recognize S.
      typhimurium var. copenhagen (LPS O:1, 4, and 12). The MAbs reacted equally with
      live and heat-attenuated Salmonella B serovars containing LPS O-5 antigen. The
      ability of the MAbs to detect live bacterial cells was further confirmed by
      transmission electron microscopy. Treatment of bacteria with cholic acid and
      extremely low pH did not affect antibody binding to S. typhimurium. However, when
      S. typhimurium cells were exposed to alkaline conditions prior to reaction with
      all three MAbs, no binding was observed. The use of MAbs to discriminate between
      S. typhimurium and S. typhimurium var. copenhagen in meat samples was
      investigated.

PMID- 8572686
TI  - Pseudomonas fluorescens adhesion and transport through porous media are affected
      by lipopolysaccharide composition.
AB  - The objectives of this work were (i) to use transposon mutagenesis to produce
      mutants of Pseudomonas fluorescens that were altered in adhesion ability and
      transport through porous media and (ii) to identify the alterations in surface
      characteristics that were responsible for the changes in attachment. Mutants of
      P. fluorescens were generated with TnphoA, which enabled identification of
      mutants that were altered in surface proteins. Transposon mutants were screened
      for alterations in adhesion ability by attachment assays on hydrophobic
      polystyrene and water-wettable polystyrene. Four TnphoA mutants with increased
      adhesion to the hydrophobic surface and decreased adhesion to the water-wettable
      surface were obtained. Transport of the strains through porous media was
      evaluated by passing suspensions of each mutant and the parent through columns
      containing quartz sand and determining the number of cells retained in the
      columns. The mutants all demonstrated increased adhesion and retention in the
      columns. Southern analysis demonstrated two types of mutants with separate
      transposon insertion sites. Polyacrylamide gel electrophoresis of the strains
      demonstrated that the O antigen on the lipopolysaccharide was either attenuated
      or absent. Lack of this polysaccharide, and the consequent increased exposure of
      the lipid moiety of the lipopolysaccharide, is probably responsible for the
      increase in adhesion to the hydrophobic substrata and retention in the sand
      column. This work combined with previous studies of attachment of P. fluorescens
      demonstrates that more than one type of polymer can mediate the adhesion of this
      organism to nonbiological surfaces.

PMID- 8572687
TI  - Effect of signal peptide alterations and replacement on export of xylanase A in
      Streptomyces lividans.
AB  - Starting from its translation initiation site, the Streptomyces lividans xylanase
      A signal peptide consists of 41 amino acids. This signal peptide was deleted and
      successively replaced with one of six signal peptides from other enzymes secreted
      by S. lividans and by a signal peptide from the outer membrane protein (LamB) of
      Escherichia coli. Deletion of the xylanase A signal peptide or modification of
      its cleavage site abolished secretion of the enzyme. Replacement with the signal
      peptides of either xylanase B, cellulase A, mannanase, or acetylxylan esterase
      produced equivalent amounts of xylanase A, while the signal peptides of cellulase
      B, xylanase C, and LamB secreted less enzyme than did the wild type. All the
      clones exhibited the same transcription levels, which indicated that the
      variations in xylanase production were due to the natures of the signal
      sequences.

PMID- 8572688
TI  - Potential virulence of viable but nonculturable Shigella dysenteriae type 1.
AB  - We examined a virulent strain of Shigella dysenteriae type 1 after induction into
      the viable but nonculturable (VBNC) state for its ability to (i) maintain the
      Shiga toxin (stx) gene; (ii) maintain biologically active Shiga toxin (ShT); and
      (iii) adhere to intestinal epithelial cells (Henle 407 cell line). PCR was used
      to amplify the stx gene from VBNC cells of S. dysenteriae type 1, thereby
      establishing its presence even when cells are in the VBNC state. VBNC S.
      dysenteriae type 1 ShT was monitored by the enzyme-linked immunosorbent assay
      with mouse monoclonal antibodies against the B subunit of ShT and affinity
      purified rabbit polyclonal antibodies against ShT. We used the Henle 407 cell
      line to study the adhesive property of VBNC S. dysenteriae type 1 cells in a
      series of tissue culture experiments. Results showed that VBNC S. dysenteriae
      type 1 not only maintained the stx gene and biologically active ShT but also
      remained capable of adhering to Henle 407 cells. However, S. dysenteriae type 1
      cells lost the ability to invade Henle 407 cells after entering the VBNC state.
      From results of the study, we conclude that VBNC cells of S. dysenteriae type 1
      retain several virulence factors and remain potentially virulent, posing a public
      health problem.

PMID- 8572690
TI  - Degradation of pyrene, benz[a]anthracene, and benzo[a]pyrene by Mycobacterium sp.
      strain RJGII-135, isolated from a former coal gasification site.
AB  - The degradation of three polycyclic aromatic hydrocarbons (PAH), pyrene (PYR),
      benz[a]anthracene (BAA), and benzo[a]pyrene (BaP), by Mycobacterium sp. strain
      RJGII-135 was studied. The bacterium was isolated from an abandoned coal
      gasification site soil by analog enrichment techniques and found to mineralize
      [14C]PYR. Further degradation studies with PYR showed three metabolites formed by
      Mycobacterium sp. strain RJGII-135, including 4,5-phenanthrene-dicarboxylic acid
      not previously isolated, 4-phenanthrene-carboxylic acid, and 4,5-pyrene
      dihydrodiol. At least two dihydrodiols, 5,6-BAA-dihydrodiol and 10,11-BAA
      dihydrodiol, were confirmed by high-resolution mass spectral and fluorescence
      analyses as products of the biodegradation of BAA by Mycobacterium sp. strain
      RJGII-135. Additionally, a cleavage product of BAA was also isolated. Mass
      spectra and fluorescence data support two different routes for the degradation of
      BaP by Mycobacterium sp. strain RJGII-135. The 7,8-BaP-dihydrodiol and three
      cleavage products of BaP, including 4,5-chrysene-dicarboxylic acid and a dihydro
      pyrene-carboxylic acid metabolite, have been isolated and identified as
      degradation products formed by Mycobacterium sp. strain RJGII-135. These latter
      results represent the first example of the isolation of BaP ring fission products
      formed by a bacterial isolate. We propose that while this bacterium appears to
      attack only one site of the PYR molecule, it is capable of degrading different
      sites of the BAA and BaP molecules, and although the sites of attack may be
      different, the ability of this bacterium to degrade these PAH is well supported.
      The proposed pathways for biodegradation of these compounds by this Mycobacterium
      sp. strain RJGII-135 support the dioxygenase enzymatic processes reported
      previously for other bacteria. Microorganisms like Mycobacterium sp. strain RJGII
      135 will be invaluable in attaining the goal of remediation of sites containing
      mixtures of these PAH.

PMID- 8572689
TI  - Cloning and characterization of styrene catabolism genes from Pseudomonas
      fluorescens ST.
AB  - A gene bank from Pseudomonas fluorescens ST was constructed in the broad-host
      range cosmid pLAFR3 and mobilized into Pseudomonas putida PaW340. Identification
      of recombinant cosmids containing the styrene catabolism genes was performed by
      screening transconjugants for growth on styrene and epoxystyrene. Transposon
      mutagenesis and subcloning of one of the selected genome fragments have led to
      the identification of three enzymatic activities: a monooxygenase activity
      encoded by a 3-kb PstI-EcoRI fragment and an epoxystyrene isomerase activity and
      an epoxystyrene reductase activity encoded by a 2.3-kb BamHI fragment.
      Escherichia coli clones containing the 3-kb PstI-EcoRI fragment were able to
      transform styrene into epoxystyrene, and those containing the 2.3-kb BamHI
      fragment converted epoxystyrene into phenylacetaldehyde or, only in the presence
      of glucose, into 2-phenylethanol. The three genes appear to be clustered and are
      probably encoded by the same DNA strand. In E. coli, expression of the
      epoxystyrene reductase gene was under the control of its own promoter, whereas
      the expression of the other two genes was dependent on the presence of an
      external vector promoter.

PMID- 8572691
TI  - Natural transmission of Salmonella choleraesuis in swine.
AB  - This experiment was designed to study the natural transmission of Salmonella
      choleraesuis in swine. Forty pigs were divided into three groups. Group 1 (n =
      12) was challenged with 10(8) CFU of S. choleraesuis per ml by intranasal
      inoculation. One day postinoculation (p.i.), group 2 (n = 24) was commingled with
      group 1. Group 3 (n = 4) served as uninoculated controls. Serum samples were
      collected weekly. Blastogenesis assays and necropsies were performed at 1, 2, 4,
      6, 9, and 12 weeks p.i., and 16 tissue samples per pig were collected and
      cultured. Environmental (pooled feces from the pen floor) levels of S.
      choleraesuis were 2.61 log10 CFU/g of feces at 24 h p.i. (immediately prior to
      commingling). Severe clinical signs were observed in groups 1 and 2. The results
      indicated that at least 16% of group 2 pigs were shedding S. choleraesuis within
      24 h of commingling. At 1 week p.i., 32 of 32 group 1 and 39 of 62 group 2 tissue
      samples were positive for S. choleraesuis. Only 3 of 12 group 2 pigs were
      positive at 6, 9, and 12 weeks (1 pig for each week), indicating that only a
      small proportion of infected swine become long-term carriers. At 12 weeks p.i.,
      only the colon and colonic lymph node samples of one pig from group 2 were
      positive. Humoral, mucosal, and cellular immune responses were similar between
      groups 1 and 2. These data demonstrate that a few pigs shedding low levels of
      Salmonella organisms before slaughter can result in rapid transmission and
      subsequent shedding by many swine.

PMID- 8572692
TI  - Phylogenetic position of yeastlike endosymbionts of anobiid beetles.
AB  - The Anobiid beetles Stegobium paniceum and Lasioderma serricorne possess the
      intracellular yeastlike symbionts Symbiotaphrina buchneri and Symbiotaphrina
      kochii, respectively, in the mycetome between the foregut and midgut. The
      nucleotide sequences of the small-subunit rRNA-encoding genes of the symbionts
      were determined for phylogenetic analysis. Five group I introns were found in the
      small-subunit rRNA-encoding genes of S. buchneri, but S. kochii lacked introns.
      The phylogenetic position of both symbionts was close to the class Discomycetes,
      which is a paraphyletic group. The two symbionts formed a monophyletic group
      distinct from the other major lineages. Both appear to have parted from other
      filamentous fungi during the early radiation of the euascomycetes and to have
      later become obligatory partners of the beetles.

PMID- 8572693
TI  - Purification and characterization of two arabinofuranosidases from solid-state
      cultures of the fungus Penicillium capsulatum.
AB  - Two arabinofuranosidases, termed Ara I and Ara II, from solid-state cultures of
      Penicillium capsulatum were purified to apparent homogeneity as judged by
      electrophoresis and isoelectric focusing. Each enzyme is a single subunit
      glycoprotein, and they have M(r)s and pIs of 64,500 and 4.15 (Ara I) and 62,700
      and 4.54 (Ara II), respectively. Ara I is most active at pH 4.0 and 60 degrees C,
      while Ara II exhibits optimal activity at pH 4.0 and 55 degrees C. Ara I is the
      more thermostable, with its half-life at 70 degrees C and pH 4.0 being 17.5 min.
      By contrast, the half-life of Ara II is only 9 min at 60 degrees C and pH 4.0.
      Ara I has the lower Km and higher catalytic constant values with p-nitrophenyl
      alpha-L-arabinofuranoside being used as the substrate. Arabinose, a competitive
      inhibitor (Ki, 16.4 mM) of Ara II, has no effect on Ara I activity at
      concentrations of up to 40 mM. Each enzyme catalyzes the release of arabinose
      from pectin, araban, and certain arabinose-containing xylans. The last activity
      is enhanced by pretreatment of the relevant substrates with xylanase, ferulic
      acid esterase, or combinations of these enzymes. Thus,
      arabinoxylooligosaccharides in which arabinose is the sole side chain substituent
      appear to be the preferred substrates. On the basis of the evidence cited above,
      each enzyme has been classified as an alpha-L-arabinofuranoside
      arabinofuranohydrolase (EC 3.2.1.79).

PMID- 8572694
TI  - Structure and function of fas-1A, a gene encoding a putative fatty acid
      synthetase directly involved in aflatoxin biosynthesis in Aspergillus
      parasiticus.
AB  - A novel gene, fas-1A, directly involved in aflatoxin B1 (AFB1) biosynthesis, was
      cloned by genetic complementation of an Aspergillus parasiticus mutant strain,
      UVM8, blocked at two unique sites in the AFB1 biosynthetic pathway. Metabolite
      conversion studies localized the two genetic blocks to early steps in the AFB1
      pathway (nor-1 and fas-1A) and confirmed that fas-1A is blocked prior to nor-1.
      Transformation of UVM8 with cosmids NorA and NorB restored function in nor-1 and
      fas-1A, resulting in synthesis of AFB1. An 8-kb SacI subclone of cosmid NorA
      complemented fas-1A only, resulting in accumulation of norsolorinic acid. Gene
      disruption of the fas-1A locus blocked norsolorinic acid accumulation in A.
      parasiticus B62 (nor-1), which normally accumulates this intermediate. These data
      confirmed that fas-1A is directly involved in AFB1 synthesis. The predicted amino
      acid sequence of fas-1A showed a high level of identity with extensive regions in
      the enoyl reductase and malonyl/palmityl transferase functional domains in the
      beta subunit of yeast fatty acid synthetase. Together, these data suggest that
      fas-1A encodes a novel fatty acid synthetase which synthesizes part of the
      polyketide backbone of AFB1. Additional data support an interaction between AFB1
      synthesis and sclerotium development.

PMID- 8572695
TI  - Use of a modified Bacteroides-Prevotella shuttle vector to transfer a
      reconstructed beta-1,4-D-endoglucanase gene into Bacteroides uniformis and
      Prevotella ruminicola B(1)4.
AB  - A carboxymethyl cellulase (CMCase) gene from Prevotella ruminicola B(1)4 was
      reconstructed by adding a cellulose binding domain from a Thermomonospora fusca
      cellulase and was conjugally transferred from Escherichia coli to Bacteroides
      uniformis 0061 by using a chloramphenicol and tetracycline resistance shuttle
      vector (pTC-COW). pTC-COW was specifically constructed to facilitate conjugal
      transfer of vectors from B. uniformis donors to P. ruminicola recipients. B.
      uniformis transconjugants containing CMCase constructs cloned into pTC-COW
      expressed Cmr, but they did not produce the reconstructed CMCase until a xylanase
      promoter from P. ruminicola 23 was added upstream of the CMCase (pTC-XRCMC). The
      xylanase promoter allowed the B. uniformis transconjugants to produce large
      amounts of the reconstructed CMCase, which was present on the outside surface of
      the cells. Although the reconstructed CMCase alone did not allow B. uniformis to
      grow on acid-swollen cellulose, rapid growth was observed when two exocellulases
      were added to the culture supernatant. Under these conditions, the reconstructed
      CMCase permitted faster growth than the wild-type CMCase. The frequency of
      transfer of pTC-XRCMC from B. uniformis to P. ruminicola B(1)4 was increased 100
      fold when strictly anaerobic conditions, nitrocelluose filters (cell
      immobilization), and more stringent selections were employed. Although the P.
      ruminicola B(1)4 (pTC-XRCMC) transconjugates expressed Tcr and had DNA that
      hybridized with a probe to the shuttle vector, these transconjugants did not
      produce detectable levels of the reconstructed CMCase even when xylan was the
      carbon source. On the basis of these results, it appears that not all of the
      promoters recognized by B. uniformis and P. ruminicola 23 are functional in P.
      ruminicola B(1)4. However, the results with B. uniformis suggest that the
      introduction of a P. ruminicola B(1)4 promoter should allow expression of the
      reconstructed CMCase in P. ruminicola B(1)4.

PMID- 8572696
TI  - Adsorption characteristics of cellulolytic enzymes from the anaerobic fungus
      Piromyces sp. strain E2 on microcrystalline cellulose.
AB  - Characteristics of the cellulolytic system of the anaerobic fungus Piromyces sp.
      strain E2 with respect to adsorption onto microcrystalline cellulose were
      examined. Cellulolytic enzymes were separated by gel filtration chromatography
      into a high-molecular-mass complex with an apparent mass of approximately 1,200
      to 1,400 kDa and proteins of lower molecular weights. Adsorption of cellulolytic
      enzymes was not only very fast (within 2 min, equilibrium was attained) but also
      very effective: Avicelase, endoglucanase, and beta-glucosidase activities from
      the high-molecular-mass complex were almost completely removed by Avicel.
      Adsorption of these enzyme activities was proportional and appeared to obey the
      Langmuir isotherm. For Avicelase, endoglucanase, and beta-glucosidase activities,
      the maximum amounts adsorbed (Amax) and apparent adsorption constants (Kad) were
      16.8, 600, and 33.5 IU/g and 284, 6.93 and 126 ml/IU, respectively. The results
      of this study strongly support the existence of a multiprotein enzyme complex.
      This complex was found not to be specifically associated with cell wall fragments
      as judged by chitin determination.

PMID- 8572697
TI  - Comparison of the recoveries of Escherichia coli and total coliforms from
      drinking water by the MI agar method and the U.S. Environmental Protection Agency
      approved membrane filter method.
AB  - Drinking water regulations under the Final Coliform Rule require that total
      coliform-positive drinking water samples be examined for the presence of
      Escherichia coli or fecal coliforms. The current U.S. Environmental Protection
      Agency-approved membrane filter (MF) method for E. coli requires two media, an MF
      transfer, and a total incubation time of 28 h. A newly developed MF method, the
      MI agar method, containing indoxyl-beta-D-glucuronide and 4-methylumbelliferyl
      beta-D-galactopyranoside for the simultaneous detection of E. coli and total
      coliforms, respectively, by means of their specific enzyme reactions, was
      compared with the approved method by the use of wastewater-spiked tap water
      samples. Overall, weighted analysis of variance (significance level, 0.05) showed
      that the new medium recoveries of total coliforms and E. coli were significantly
      higher than those of mEndo agar and nutrient agar plus MUG (4-methylumbelliferyl
      beta-D-glucuronide), respectively, and the background counts were significantly
      lower than those of mEndo agar (< 5%). Generally, the tap water source, overall
      chlorine level, wastewater source, granular activated carbon treatment of the tap
      water, and method of grouping data by E. coli count for statistical analysis did
      not affect the performance of the new medium.

PMID- 8572698
TI  - Expression of Aureobasidium pullulans xynA in, and secretion of the xylanase
      from, Saccharomyces cerevisiae.
AB  - A previous report dealt with the cloning in Escherichia coli and sequencing of
      both the cDNA and genomic DNA encoding a highly active xylanase (XynA) of
      Aureobasidium pullulans (X.-L. Li and L. G. Ljungdahl, Appl. Environ. Microbiol.
      60:3160-3166, 1994). Now we show that the gene was expressed in Saccharomyces
      cerevisiae under the GAL1 promoter in pYES2 and that its product was secreted
      into the culture medium. S. cerevisiae clone pCE4 with the whole open reading
      frame of xynA, including the part coding for the signal peptide, had xylanase
      activity levels of 6.7 U ml-1 in the cell-associated fraction and 26.2 U ml-1 in
      the culture medium 4 h after galactose induction. Two protein bands with sizes of
      25 and 27 kDa and N-terminal amino acid sequences identical to that of APX-II
      accounted for 82% of the total proteins in the culture medium of pCE4. These
      proteins were recognized by anti-APX-II antibody. The results suggest that the
      XynA signal peptide supported the posttranslational processing of xynA product
      and the efficient secretion of the active xylanase from S. cerevisiae. Clones
      pCE3 and pGE3 with inserts of cDNA and genomic DNA, respectively, containing only
      the mature enzyme region attached by a Met codon had low levels of xylanase
      activity in the cell-associated fractions (1.6 U ml-1) but no activity in the
      culture media. No xylanase activity was detected in clone pGE4, which was the
      same as pCE4, except that pGE4 had a 59-bp intron in the signal peptide region. A
      comparison of the A. pullulans and S. cerevisiae signal peptides demonstrated
      that the XynA signal peptide was at least three times more efficient than those
      of S. cerevisiae invertase or mating alpha-factor pheromone in secreting the
      heterologous xylanase from S. cerevisiae cells.

PMID- 8572699
TI  - Nondisruptive detection of activity of catabolic promoters of Pseudomonas putida
      with an antigenic surface reporter system.
AB  - A simple procedure to detect the switching on and off of catabolic promoters of
      Pseudomonas putida, at the level of single cells based on the immunodetection of
      a reporter epitope expressed on the surface of bacterial cells, has been
      developed. To do this, the antigenic sequence Asp-Leu-Pro-Pro-Asn-Ser-Asp-Val-Val
      Asp, from a coronavirus, was inserted genetically in the permissive site around
      amino acid position 153 of the LamB protein (maltose and lambda phage receptor)
      of Escherichia coli. When the hybrid lamB gene is transcribed, the epitope
      becomes presented on the surface of the bacterial cells in a configuration
      available to specific antibodies. To validate this notion in nonenteric bacteria,
      the expression and correct processing of LamB were confirmed by coupling the lamB
      gene to the salicylate-responsive Psa1 promoter of the NAH7 (naphthalene
      degradation) plasmid in Pseudomonas putida. Subsequently, a hybrid lamB gene
      carrying the sequence of the coronavirus antigen was placed downstream of the m
      toluate-responsive Pm promoter of the TOL (toluene degradation) plasmid. Exposure
      of the epitope on the Pseudomonas cell surface was monitored through fluorescence
      of whole cells treated with a monoclonal antibody against the heterologous
      antigen. Fluorescence emission was dependent on the presence of m-toluate in the
      medium, thus permitting detection of the Pm promoter switching on by simple
      optical inspection of individual cells, even in situations when these are a very
      minor component of a complex bacterial community.

PMID- 8572700
TI  - Isolation, DNA sequence analysis, and mutagenesis of a proline dehydrogenase gene
      (putA) from Bradyrhizobium japonicum.
AB  - We report here the cloning and sequencing of the gene for proline dehydrogenase
      (putA) of Bradyrhizobium japonicum. An open reading frame coding for 1,016 amino
      acids was identified. The B. japonicum gene codes for a bifunctional protein with
      proline dehydrogenase and pyrroline-5-carboxylate (P5C) dehydrogenase activities,
      as it does in Escherichia coli and Salmonella typhimurium. Comparison of the
      sequences of these proteins with other proline and P5C dehydrogenase sequences
      identified proline dehydrogenase and P5C dehydrogenase catalytic domains. Within
      the proline dehydrogenation domain, several areas of high identity were observed
      between B. japonicum, E. coli, S. typhimurium, Saccharomyces cerevisiae put1, and
      Drosophila melanogaster slgA. Within the P5C dehydrogenase domain, several areas
      of high identity were observed between B. japonicum, E. coli, S. typhimurium,
      Bacillus subtilis ipa76d, and S. cerevisiae put2. A consensus catalytic site for
      semialdehyde dehydrogenase was observed in the P5C dehydrogenase domain. This
      suggests that the substrate for this domain may be the open-chain gamma
      glutamylsemialdehyde, not its cyclized form, P5C. Unlike the gene isolated from
      E. coli, S. typhimurium, and K. pneumoniae, the B. japonicum putA gene does not
      appear to be part of an operon with the proline porter gene (putP). Additionally,
      the B. japonicum gene lacks the putative C-terminal regulatory domain present in
      the E. coli and S. typhimurium genes. The gene was disrupted by insertion of
      antibiotic resistance gene cassettes, which were then recombined into the
      bacterial chromosome. Symbiotically active mutant strains that were devoid of
      putA activity were isolated. With this proline dehydrogenase clone, we will test
      the hypothesis that putA in symbiotic nitrogen-fixing B. japonicum bacteroids is
      transcriptionally regulated by drought and other stresses.

PMID- 8572701
TI  - Molecular cloning of novel genes for polycyclic aromatic hydrocarbon degradation
      from Comamonas testosteroni GZ39.
AB  - Three strains of Comamonas testosteroni were isolated from river sediment for the
      ability to degrade phenanthrene; two of the strains also grew on naphthalene, and
      one strain also grew on anthracene. The homology of the genes for polycyclic
      aromatic hydrocarbon degradation in these strains to the classical genes (nah)
      for naphthalene degradation from Pseudomonas putida NCIB 9816-4 was determined.
      The three C. testosteroni strains showed no homology to the nah gene probe even
      under low-stringency conditions. The genes for naphthalene and phenanthrene
      degradation were cloned from one of the three C. testosteroni strains. Two cosmid
      clones expressing polycyclic aromatic hydrocarbon dioxygenase activity were
      identified from a library prepared with genomic DNA from C. testosteroni GZ39.
      The genes coding for the first two enzymes in the catabolic pathway, phenanthrene
      dioxygenase and cis-phenanthrene dihydrodiol dehydrogenase, were localized to a
      5.4-kb NcoI-PstI fragment by subcloning and gene expression experiments. Further
      subcloning and analysis revealed a novel organization of the genes, with the gene
      for cis-phenanthrene dihydrodiol dehydrogenase located between the genes for the
      individual phenanthrene dioxygenase components. A Southern blot with the cloned
      genes from C. testosteroni GZ39 confirmed that these genes are distinct from
      those found in P. putida NCIB 9816-4. Southern blots also demonstrated that C.
      testosteroni GZ38A possesses genes for phenanthrene degradation that are similar
      to those cloned from C. testosteroni GZ39. However, C. testosteroni GZ42
      possesses genes for phenanthrene degradation that are not homologous to those
      cloned from C. testosteroni GZ39. This suggests that there are at least two
      different sets of genes for the degradation of phenanthrene among the three C.
      testosteroni strains.

PMID- 8572703
TI  - Genetic structures of the genes encoding 2,3-dihydroxybiphenyl 1,2-dioxygenase
      and 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid hydrolase from biphenyl- and 4
      chlorobiphenyl-degrading Pseudomonas sp. strain DJ-12.
AB  - The pcbC and pcbD genes of Pseudomonas sp. strain DJ-12, a natural isolate
      degrading biphenyl and 4-chlorobiphenyl, encode the 2,3-dihydroxybiphenyl 1,2
      dioxygenase and 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid hydrolase,
      respectively. The two genes were sequenced and appear to be present in the order
      pcbD-pcbC as an operon.

PMID- 8572702
TI  - Collaborative evaluation of a method for the detection of Norwalk virus in
      shellfish tissues by PCR.
AB  - A multicenter, collaborative trial was performed to evaluate the reliability and
      reproducibility of a previously described method for the detection of Norwalk
      virus in shellfish tissues with the PCR (R.L. Atmar, F. H. Neill, J. L. Romalde,
      F. Le Guyader, C. M. Woodley, T. G. Metcalf, and M. K. Estes, Appl. Environ.
      Microbiol. 61:3014-3018, 1995). Virus was added to the stomachs and
      hepatopancreatic tissues of oysters or hard-shell clams in the control
      laboratory, the samples were shipped to the participating laboratories, and viral
      nucleic acids were extracted and then detected by reverse transcription-PCR. The
      sensitivity and specificity of the assay were 85 and 91%, respectively, when
      results were determined by visual inspection of ethidium bromide-stained agarose
      gels; the test sensitivity and specificity improved to 87 and 100%, respectively,
      after confirmation by hybridization with a digoxigenin-labeled, virus-specific
      probe. We have demonstrated that this method can be implemented successfully by
      several laboratories to detect Norwalk virus in shellfish tissues.

PMID- 8572704
TI  - Transferable erythromycin resistance in Listeria spp. isolated from food.
AB  - An erythromycin-resistant (Emr) Listeria innocua and an Emr Listeria
      monocytogenes isolate both carried ermC genes, which code for rRNA methylases.
      The ermC genes were transferable by conjugation to recipient L. monocytogenes,
      Listeria ivanovii, and Enterococcus faecalis but did not appear to be associated
      with conjugative plasmids.

PMID- 8572705
TI  - Molecular analysis of environmental and human isolates of Salmonella typhi.
AB  - Molecular characterization of a total of 54 isolates of Salmonella typhi from
      Santiago, Chile, was performed by pulsed-field gel electrophoresis (PFGE) after
      digestion of chromosomal DNA with three restriction endonucleases: XbaI (5'
      TCTAGA-3'), AvrII (5'-CCTAGG-3'), and SpeI (5'-ACTAGT-3'). Thirteen of the 54
      isolates were obtained from environmental sources (sewage and river water), and
      the rest were isolates from clinical cases of typhoid fever. Considerable genetic
      diversity was detected among the human isolates obtained in 1994, as evidenced by
      the presence of 14 to 19 different PFGE patterns among 20 human isolates, with F
      (coefficient of similarity) values ranging from 0.69 to 1.0 (XbaI), 0.61 to 1.0
      (AvrII), and 0.70 to 1.0 (SpeI). A total of eight phage types were detected among
      these 20 isolates, with 50% possessing the E1 or 46 phage type. There was no
      correlation between PFGE pattern and phage types. Similar diversity was seen
      among 21 isolates obtained in 1983, with 17 to 19 PFGE patterns detected and F
      values of 0.56 to 1.0 (XbaI), 0.55 to 1.0 (AvrII), and 0.67 to 1.0 (SpeI).
      Comparison of these two groups of human isolates obtained 11 years apart
      indicated that certain molecular types of S. typhi are shared and are able to
      persist for considerable periods. A similar degree of genetic diversity was also
      detected among the environmental isolates of S. typhi, for which 10 to 12
      different PFGE patterns were detected among the 13 isolates analyzed, with F
      values ranging from 0.56 to 1.0 (XbaI), 0.52 to 1.0 (AvrII), and 0.69 to 1.0
      (SpeI). Certain molecular types present among the environmental isolates of S.
      typhi were also found among the human isolates from the same time period,
      providing evidence for the epidemiological link between environmental reservoirs
      and human infection.

PMID- 8572706
TI  - Detection of specific bacterial cells with 2-hydroxy-3-naphthoic acid-2'
      phenylanilide phosphate and fast red TR in situ hybridization.
AB  - An in situ hybridization technique with HNPP (2-hydroxy-3-naphthoic acid-2'
      phenylanilide phosphate) and Fast Red TR was used to detect specific bacterial
      cells at the single-cell level. By this technique, the fluorescent signals of
      target bacterial cells were up to eight times more intense than those of standard
      fluorescence in situ hybridization with mono-fluorescein isothiocyanate-labeled
      oligonucleotide probes. This novel HNPP-Fast Red TR whole-cell hybridization
      technique is available for the identification of small or low-rRNA-content
      bacterial cells in the natural environment.

PMID- 8572707
TI  - Site-directed mutations in the third domain of Bacillus thuringiensis delta
      endotoxin CryIAa affect its ability to increase the permeability of Bombyx mori
      midgut brush border membrane vesicles.
AB  - A series of mutant Bacillus thuringiensis CryIAa delta-endotoxin proteins was
      prepared by replacing the first, second, and last arginine residues of the
      conserved third-domain sequence, R-521 YRVRIR-527, with other amino acids. The
      stable mutant proteins were bioassayed against Bombyx mori larvae and found to
      all be approximately half as active as wild-type CryIAa. The toxins were also
      tested by means of a light-scattering assay for their ability to increase
      permeability of larval B. mori midgut brush border membrane vesicles. Three of
      the mutant toxins were as active as the wild-type toxin in the vesicle
      permeability assay.

PMID- 8572708
TI  - Occurrence of airborne bacteria and pathogen indicators during land application
      of sewage sludge.
AB  - Glass impingers (AGI-30) were used at a commercial sludge application site to
      determine the levels of airborne bacteria and pathogen indicators. Even though
      heterotrophic bacteria averaged 10(5) CFU/m3, none of the sites showed the
      presence of Salmonella spp. or indicators such as fecal coliforms or coliphages.
      Indicators such as H2S producers and pathogenic clostridia were present in
      locations having significant physical agitation of the sludge material. PCR-based
      ribotyping using the 16S-23S interspacer region is a promising method to identify
      the genetic relatedness and origins of airborne clostridia.

PMID- 8572709
TI  - Aerobic and anaerobic metabolism of Listeria monocytogenes in defined glucose
      medium.
AB  - A defined medium with glucose as the carbon source was used to quantitatively
      determine the metabolic end products produced by Listeria monocytogenes under
      aerobic and anaerobic conditions. Of 10 strains tested, all produced acetoin
      under aerobic conditions but not anaerobic conditions. Percent carbon recoveries
      of end products, typified by strain F5069, were as follows: lactate, 28%;
      acetate, 23%; and acetoin, 26% for aerobic growth and lactate, 79%; acetate, 2%;
      formate, 5.4%; ethanol, 7.8%; and carbon dioxide, 2.3% for anaerobic growth. No
      attempt to determine carbon dioxide under aerobic growth conditions was made. The
      possibility of using acetoin production to assay for growth of L. monocytogenes
      under defined conditions should be considered.

PMID- 8572710
TI  - Evaluation of molecular typing techniques to assign genetic diversity among
      Saccharomyces cerevisiae strains.
AB  - Discrimination of strains within the species Saccharomyces cerevisiae was
      demonstrated by the use of four different techniques to type 15 strains isolated
      from spoiled wine and beer. Random amplified polymorphic DNA with specific
      oligonucleotides and PCR fingerprinting with the microsatellite oligonucleotide
      primers (GAC)5 and (GTG)5 enabled discrimination between the strains tested.
      Additionally, restriction enzyme analysis, with TaqI and MseI, of PCR-amplified
      fragments from the complete internal transcribed spacer and nontranscribed
      spacer, both present in the rRNA-encoding gene cluster, proved to be suitable for
      generating intraspecies-specific patterns. Random amplified polymorphic DNA with
      primers 24 and OPA-11 and PCR fingerprinting with primer (GTG)5 appeared to
      generate the highest degree of diversity. However, the results indicated that
      there was no single PCR-mediated typing technique enabling discrimination on the
      strain level. Discrimination of each individual strain was nevertheless possible
      by combining the results obtained with all typing techniques.

PMID- 8572711
TI  - Longitudinal studies of Giardia contamination in two community drinking water
      supplies: cyst levels, parasite viability, and health impact.
AB  - Giardia cyst concentrations were determined in an inventory of 153 raw and 91
      chlorinated drinking water samples collected at 86 sites from throughout the
      western Canadian province of British Columbia. Sixty-four percent of raw water
      samples were cyst positive (69% of sites). Cyst concentrations were lower in
      chlorinated than in raw water. The viability of cysts in drinking water samples
      assessed by infectivity in Mongolian gerbils (Meriones unguiculatus) was
      decreased in chlorinated water. Two rural communities using Giardia-contaminated
      surface drinking water sources were selected for longitudinal studies including
      drinking water testing and serological studies of residents. Three hundred thirty
      six raw and treated samples from these communities were collected over 24 months.
      Cyst concentrations and viability were assessed in a 12-month study of each
      community. Parasite concentrations were lower in chlorinated water than in raw
      water in both communities. Cyst concentrations were lower in reservoir-settled
      water than in raw water. Viability, assessed by animal infectivity and corrected
      for inoculum, decreased following reservoir settling as well as after
      chlorination. A bolus or spiking phenomenon of cysts was observed in both
      community drinking water systems and deserves further study. A striking seasonal
      pattern was seen in one community but not in the second. The seroprevalence data
      and number of laboratory-confirmed cases identified in each year-long community
      study are consistent with the possibility that low-level endemic transmission is
      occurring.

PMID- 8572712
TI  - Combined effects of the signal sequence and the major chaperone proteins on the
      export of human cytokines in Escherichia coli.
AB  - We have studied the export of two human proteins in the course of their
      production in Escherichia coli. The coding sequences of the granulocyte
      macrophage colony-stimulating factor and of interleukin 13 were fused to those of
      two synthetic signal sequences to direct the human proteins to the bacterial
      periplasm. We found that the total amount of protein varies with the signal
      peptide-cytokine combination, as does the fraction of it that is soluble in a
      periplasmic extract. The possibility that the major chaperone proteins such as
      SecB and the GroEL-GroES and DnaK-DnaJ pairs are limiting factors for the export
      was tested by overexpressing one or the other of these chaperones concomitantly
      with the heterologous protein. The GroEL-GroES chaperone pair had no effect on
      protein production. Overproduction of SecB or DnaK plus DnaJ resulted in a marked
      increase of the quantity of human proteins in the periplasmic fraction, but this
      increase depends on the signal peptide-heterologous protein-chaperone association
      involved.

PMID- 8572713
TI  - Aliphatic and chlorinated alkenes and epoxides as inducers of alkene
      monooxygenase and epoxidase activities in Xanthobacter strain Py2.
AB  - The inducible nature of the alkene oxidation system of Xanthobacter strain Py2
      has been investigated. Cultures grown with glucose as the carbon source did not
      contain detectable levels of alkene monooxygenase or epoxidase, two key enzymes
      of alkene and epoxide metabolism. Upon addition of propylene to glucose-grown
      cultures, alkene monooxygenase and epoxidase activities increased and after an 11
      h induction period reached levels of specific activity comparable to those in
      propylene-grown cells. Addition of chloramphenicol or rifampin prevented the
      increase in the enzyme activities. Comparison of the banding patterns of proteins
      present in cell extracts revealed that polypeptides with molecular masses of 43,
      53, and 57 kDa accumulate in propylene-grown but not glucose-grown cells. Pulse
      labeling of glucose-grown cells with [35S]methionine and [35S]cysteine revealed
      that the 43-, 53-, and 57-kDa proteins, as well as two additional polypeptides
      with molecular masses of 12 and 21 kDa, were newly synthesized upon exposure of
      cells to propylene or propylene oxide. The addition to glucose-grown cells of a
      variety of other aliphatic and chlorinated alkenes and epoxides, including
      ethylene, vinyl chloride (1-chloroethylene), cis- and trans-1,2-dichloroethylene,
      1-chloropropylene, 1,3-dichloropropylene, 1-butylene, trans-2-butylene,
      isobutylene, ethylene oxide, epichlorohydrin (3-chloro-1,2-epoxypropane), 1,2
      epoxybutane, cis- and trans-2,3-epoxybutane, and isobutylene oxide stimulated the
      synthesis of the five propylene-inducible polypeptides as well as increases in
      alkene monooxygenase and epoxidase activities. In contrast, acetylene, and a
      range of aliphatic and chlorinated alkanes, did not stimulate the synthesis of
      the propylene-inducible polypeptides or the increase in alkene monooxygenase and
      epoxidase activities.

PMID- 8572714
TI  - Description of a new polymer-secreting bacterium from a deep-sea hydrothermal
      vent, Alteromonas macleodii subsp. fijiensis, and preliminary characterization of
      the polymer.
AB  - A deep-sea, aerobic, mesophilic, heterotrophic bacterium was isolated from fluid
      collected near an active hydrothermal vent. On the basis of phenotypic and
      phylogenetic analyses and DNA-DNA relatedness, strain ST716 could be assigned to
      the species Alteromonas macleodii as a new subspecies. This bacterium secreted an
      unusual high-molecular-weight polysaccharide in the presence of glucose in batch
      cultures. The viscosity of this exopolysaccharide is of the same order of
      magnitude as that of xanthan, another bacterial polysaccharide of industrial
      interest. This polysaccharide, produced during the stationary phase, contained
      glucose, mannose, pyruvated mannose, and galactose along with galacturonic acid
      and glucuronic acid.

PMID- 8572715
TI  - A Bacillus thuringiensis insecticidal crystal protein with a high activity
      against members of the family Noctuidae.
AB  - The full characterization of a novel insecticidal crystal protein, named Cry9Ca1
      according to the revised nomenclature for Cry proteins, from Bacillus
      thuringiensis serovar tolworthi is reported. The crystal protein has 1,157 amino
      acids and a molecular mass of 129.8 kDa. It has the typical features of the
      Lepidoptera-active crystal proteins such as five conserved sequence blocks. Also,
      it is truncated upon trypsin digestion to a toxic fragment of 68.7 kDa by removal
      of 43 amino acids at the N terminus and the complete C-terminal half after
      conserved sequence block 5. The 68.7-kDa fragment is further degraded to a
      nontoxic 55-kDa fragment. The crystal protein has a fairly broad spectrum of
      activity against lepidopteran insects, including members of the families
      Pyralidae, Plutellidae, Sphingidae, and Noctuidae. A 50% lethal concentration of
      less than 100 ng/cm2 of diet agar was found for diamondback moth, European corn
      borer, cotton bollworm, and beet armyworm. It is the first insecticidal crystal
      protein with activity against cutworms. No activity was observed against some
      beetles, such as Colorado potato beetle. The protein recognizes a receptor
      different from that recognized by Cry1Ab5 in Ostrinia nubilalis and Plutella
      xylostella. In Spodoptera exigua and P. xylostella, it binds to a receptor which
      is also recognized by Cry1Cax but with a lower affinity. In these insects,
      Cry1Cax probably binds with a higher affinity to an additional receptor which is
      not recognized by Cry9Ca1. Elimination of a trypsin cleavage site which is
      responsible for the degradation to a nontoxic fragment did result in protease
      resistance but not in increased toxicity against O. nubilalis.

PMID- 8572716
TI  - Isolation of a species-specific mitochondrial DNA sequence for identification of
      Tilletia indica, the Karnal bunt of wheat fungus.
AB  - Mitochondrial DNA (mtDNA) from five isolates of Tilletia indica was isolated and
      digested with several restriction enzymes. A 2.3-kb EcoRI fragment was chosen,
      cloned, and shown to hybridize with total DNA restricted with EcoRI from T.
      indica and not from a morphologically similar smut fungus, Tilletia barclayana.
      The clone was partially sequenced, and primers were designed and tested under
      high-stringency conditions in PCR assays. The primer pair Ti1/Ti4 amplified a 2.3
      kb fragment from total DNA of 17 T. indica isolates from India, Pakistan, and
      Mexico. DNA from 25 isolates of other smut fungi (T. barclayana, Tilletia
      foetida, Tilletia caries, Tilletia fusca, and Tilletia controversa) did not
      produce any bands, as detected by ethidium bromide-stained agarose gels and
      Southern hybridizations. The sensitivity of the assay was determined and
      increased by using a single nested primer in a second round of amplification, so
      that 1 pg of total mycelial DNA could be detected. The results indicated that the
      primers which originated from a cloned mtDNA sequence can be used to
      differentiate T. indica from other Tilletia species and have the potential to
      identify teliospores contaminating wheat seeds.

PMID- 8572717
TI  - Degradation of cocaine by a mixed culture of Pseudomonas fluorescens MBER and
      Comamonas acidovorans MBLF.
AB  - A mixed culture that could utilize cocaine as the sole source of carbon and
      energy for growth was isolated by selective enrichment. The individual
      microorganisms within this mixed culture were identified as Pseudomonas
      fluorescens (termed MBER) and Comamonas acidovorans (termed MBLF). Each
      microorganism was shown to be unable to grow to any appreciable extent on 10 mM
      cocaine in the absence of the other. C. acidovorans MBLF was found to possess an
      inducible cocaine esterase which catalyzed the hydrolysis of cocaine to ecgonine
      methyl ester and benzoate. C. acidovorans was capable of growth on benzoate at
      concentrations below 5 mM but was unable to metabolize ecgonine methyl ester. P.
      fluorescens MBER was capable of growth on either benzoate as the sole source of
      carbon or ecgonine methyl ester as the sole source of carbon and nitrogen. P.
      fluorescens MBER was found to initiate the degradation of ecgonine methyl ester
      via ecgonine, pseudoecgonine, and pseudoecgonyl-coenzyme A. Subcellular studies
      resulted in the identification of an ecgonine methyl esterase, an ecgonine
      epimerase, and a pseudoecgonyl-coenzyme A synthetase which were induced by growth
      on ecgonine methyl ester or ecgonine. Further metabolism of the ecgonine moiety
      is postulated to involve nitrogen debridging, with the production of carbonyl
      containing intermediates.

PMID- 8572718
TI  - Acute effects of total suspended particles and sulfur dioxides on preterm
      delivery: a community-based cohort study.
AB  - The acute effects of air pollution on preterm delivery were examined in a
      prospective cohort in Beijing, China. From early pregnancy until delivery in
      1988, we followed all registered pregnant women who lived in four residential
      areas of Beijing. Information for both mothers and infants was collected. Daily
      air pollution and meteorological data were obtained independently. The sample for
      analysis included 25,370 resident women who gave first live births in 1988.
      Multiple linear regression and logistic regression were used to estimate the
      effects of air pollution on gestational age and preterm delivery (i.e., < 37 wk),
      with adjustment for outdoor temperature and humidity, day of the week, season,
      maternal age, gender of child, and residential area. Very high concentrations of
      ambient sulfur dioxide (mean = 102 micrograms/m3, maximum = 630 micrograms/m3)
      and total suspended particulates (mean = 375 micrograms/m3, maximum = 1 0003
      micrograms/m3) were observed in these areas. There was a significant dose
      dependent association between gestational age and sulfur dioxide and total
      suspended particulate concentrations. The estimated reduced duration of gestation
      was .075 wk (12.6h) and .042 wk (7.1 h) for each 100-micrograms/m3 increase in
      sulfur dioxide and total suspended particulates 7-d lagged moving average,
      respectively. The adjusted odds ratio for preterm delivery was 1.21 (95% CI =
      1.01-1.46) for each in micrograms/m3 increase in sulfur dioxide, and was 1.10
      (95% CI = 1.01-1.20) for each 100-micrograms/m3 increase in total suspended
      particulates. In addition, the gestational age distribution of high-pollution
      days was more skewed toward the left tail (i.e., very preterm and preterm),
      compared with low-pollution days. We concluded that high levels of total
      suspended particulates and sulfur dioxide, or of a more complex pollution mixture
      associated with these pollutants, appear to contribute to excess risk of preterm
      delivery in this population. Further work need to be carried out, with more
      detailed information on personal exposure and effect modifiers.

PMID- 8572719
TI  - Incidence of cancer among persons living near a municipal solid waste landfill
      site in Montreal, Quebec.
AB  - The Miron Quarry municipal solid waste landfill site in Montreal, Quebec,
      generates copious quantities of methane and other gases, including a rich mixture
      of volatile organic compounds, some of which are recognized or suspected human
      carcinogens. The site is the third largest in North America and is located in the
      center of a densely populated area. Using data from the Quebec Tumour Registry,
      we conducted Poisson regression analyses to evaluate whether cancer incidence
      among persons who lived near the site was higher than expected. Potential
      exposure to ambient air pollutants from the site was defined in terms of a set of
      geographic exposure zones proximal to the site. A set of reference areas distal
      from the site was selected to be similar to these exposure zones with respect to
      several key sociodemographic factors. Risk ratios (RRs) were adjusted for age and
      calendar year. Among men living in the exposure zone closest to the site,
      elevated risks were observed for cancers of the stomach (RR = 1.3, 95% confidence
      interval [95% CI] = 1.0-1.5); liver and intrahepatic bile ducts (RR = 1.3, 95% CI
      = 0.9-1.8); and trachea, bronchus, and lung (RR = 1.1, 95% CI = 1.0-1.2). Among
      women, rates of stomach cancer (RR = 1.2; 95% CI = 0.9-1.5) and cervix uteri
      cancer were elevated (RR = 1.2, 95% CI = 1.0-1.5), but breast cancer incidence
      was less than expected (RR = 0.9, 95% CI = 0.9-1.0). Prostate cancer was also
      elevated in one of the proximal exposure subzones (RR = 1.2, 95% CI = 1.0-1.4).
      Further studies at this and at other landfill sites are needed to confirm or
      refute these observations.

PMID- 8572720
TI  - Patients with multiple chemical sensitivities in an occupational health clinic:
      presentation and follow-up.
AB  - Thirty-five people with work-related Multiple Chemical Sensitivities were studied
      to learn about the onset and progression of illness. The subjects were selected
      from patients at an occupational health clinic. Individuals were identified as
      subjects if they fulfilled a seven-point case definition for Multiple Chemical
      Sensitivities and if onset of symptoms was related to workplace exposures. Three
      occupational exposures to solvents, poor indoor-air quality, and remodeling were
      associated with onset of Multiple Chemical Sensitivities in 63% of the subjects.
      Symptoms indicative of a nervous-system disorder topped the list of the most
      frequently reported symptoms. Commonalities in exposures and symptoms suggest
      that Multiple Chemical Sensitivities represents a distinct diagnostic category.
      Even with an incomplete understanding of etiology, it may be possible to limit
      the onset of work-related Multiple Chemical Sensitivities.

PMID- 8572721
TI  - Recovery of respiratory function in survivors with paraquat intoxication.
AB  - The purpose of this study was to investigate chest radiograms and respiratory
      function changes, including pulmonary function tests and alveolar-arterial oxygen
      difference, in survivors with paraquat intoxication. Chest radiograms and
      pulmonary function tests for 21 paraquat-poisoned patients were performed 10 d
      after paraquat intoxication; 3 mo later, the tests were repeated in 16 patients
      who survived. Forced vital capacity, forced expiratory volume in 1 s, diffusing
      capacity of the lung, and alveolar-arterial oxygen difference were compromised
      after paraquat intoxication. Forced expiratory volume in 1 s and forced vital
      capacity correlated significantly with initial platelet counts (r = .453 and
      .443, respectively) 10 d after intoxication. The alveolar-arterial oxygen
      difference also correlated significantly with peak serum total bilirubin
      concentrations (r = .443) and initial platelet counts (r = .469). The follow-up
      data for respiratory functions forced expiratory volume in 1 s; 74.33 +/- 27.1%
      versus 97.89 +/- 16.39%; forced vital capacity: 71.44 +/- 26.03% versus 93.22 +/-
      13.92%; diffusing capacity of lung: 60.11 +/- 27.61% versus 81.67 +/- 24.56%;
      alveolar-arterial oxygen difference: 37.95 +/- 24.32 mm Hg versus 7.75 +/- 9.94
      mm Hg) and chest radiograms of survivors with moderate to severe paraquat
      poisoning showed significant improvements 3 mo after intoxication. The results
      demonstrated that paraquat-induced respiratory function impairments could recover
      significantly, at least partially, with time. In addition, pulmonary structure
      damage improved, as shown in the follow-up chest radiographs.

PMID- 8572722
TI  - Chronic neurologic sequelae to cholinesterase inhibition among agricultural
      pesticide applicators.
AB  - To test the hypothesis that chronic neurologic sequelae are associated with
      cholinesterase depression short of frank organophosphate poisoning, we compared
      45 male subjects who had a history of moderate cholinesterase inhibition with 90
      male subjects who had neither past cholinesterase inhibition nor current
      pesticide exposure. Cholinesterase-inhibited subjects were defined as having had
      a history of (a) red blood cell cholinesterase at 70% or less of baseline or (b)
      plasma cholinesterase at 60% or less of baseline absent symptoms of frank
      poisoning. In the subject comparison evaluation, only 1 of 27 neurologic tests
      (i.e., serial digit performance) was significant statistically, but it was
      opposite of the direction hypothesized. In a companion study for which the same
      battery of neurologic tests and the same subjects were used, neurologic sequelae
      were related to high exposures among subjects who sought treatment for
      organophosphate poisoning. The data in the current study, in which the subjects
      experienced lower exposures short of frank poisoning, provide some evidence that
      preventing acute organophosphate poisoning also prevents neurologic sequelae.

PMID- 8572723
TI  - Exposures of health-care workers to ribavirin aerosol: a pharmacokinetic study.
AB  - We assessed health risks to nurses and therapists exposed occupationally to
      ribavirin aerosol, a known rodent teratogen, by measuring uptake as a function of
      exposure concentration. During a 4-d period, healthy, nonsmoking, young adult
      volunteers (N = 14) were exposed 4 h/d respirable ribavirin aerosol at
      concentrations that exceeded occupational levels. Intermittent exercise occurred
      during exposure, and all activities occurred in a simulated hospital room.
      Ribavirin was assayed in plasma, red cells, and urine; lung function and symptoms
      were also measured. In 7 volunteers who were exposed to 30 mg/m3 (i.e., received
      approximately 10% of therapeutic dose), postexposure ribavirin concentrations in
      plasma and urine were similar on all 4 d, averaging (0.89 mumol/l and 131
      mumol/l, respectively. These concentrations decreased after exposure, with half
      times of 37-39 h. Red-cell concentrations averaged 31 mumol/l on d 4, accounting
      for < 5% of inhaled ribavirin mass, and they remained stable for 4 d afterward.
      In 7 volunteers exposed to 3 mg/m3 (i.e., approximately 1% of therapeutic dose),
      plasma averaged 0.075 mumol/l and red cells averaged 3 mumol/l on d 4 (i.e., near
      detection limits). Small variations occurred in lung function, reported symptoms,
      and hematologic values for exposures to both 3 and 30 microgram/m3; therefore,
      these effects were most likely not caused by ribavirin. Typical occupational
      exposures to ribavirin, without recommended protective measures, should result in
      undetectable or barely detectable body burdens, i.e., approximately 0.1%-1% of
      levels reported to be toxic to laboratory animals.

PMID- 8572724
TI  - Aircraft noise, hearing ability, and annoyance.
AB  - The relationship between aircraft noise, loss of hearing, and annoyance was
      explored in a study in two schools located near an international airport in
      Taiwan. Sixth-grade students (N = 242) were recruited from two schools and were
      classified into high- and low-noise-exposure groups, based on environmental noise
      measurements. Personal-equivalent 24-h noise exposure was measured to determine
      noise exposure at the individual level, and it was compared with hearing
      threshold level and with aircraft noise measured at the environmental level.
      Individual hearing threshold levels did not differ between environmental high-
      and low-noise-exposure groups, as evidenced by the lack of difference between the
      two groups for noise exposure measured at the individual level. However, the
      proportion of students who were annoyed by aircraft noise was higher in the
      environmental high-noise-exposure group, although personal 24-h noise exposure
      was not a factor for annoyance. The results indicated that environmental noise
      measurement was not an appropriate criterion for assessment of auditory damage
      (or noise-induced hearing loss) in Taiwan. As well, aircraft-noise exposure in
      Taiwan did not appear to affect the hearing threshold but nonetheless annoyed
      schoolchildren near the airport.

PMID- 8572725
TI  - Variation of urinary pH and bicarbonate concentrations of students in
      metropolitan and rural areas of Japan.
AB  - Changes in urinary pH and bicarbonate levels were studied in urine collected
      before and after final examinations taken by 91 medical students (65 males, 26
      females) in Tokyo and from 87 students (73 males, 14 females) in Kanazawa, a
      rural municipality. Bicarbonate levels and pH in the urine of students in both
      cities increased significantly after attending 2 h of final examinations. The
      highest pH value and highest bicarbonate level were 7.66 and 80.3 mM,
      respectively, found in the urine of a student in Kanazawa. Urinary pH and
      bicarbonate levels averaged 6.48 and 11.1 mM, respectively, for students in Tokyo
      and 6.26 and 8.91 mM, respectively, for students in Kanazawa. Given that the
      concentrations of carbon dioxide in the air of the classrooms in both cities
      increased drastically during the final examinations (i.e., from 700 ppm to 1 200
      ppm in Tokyo and from 700 ppm to 1 500 ppm in Kanazawa), it appears that the
      increases in urinary pH and bicarbonate levels were correlated with the increase
      of carbon dioxide (known to be convertible to bicarbonate in blood) in the rooms.
      This was also supported by the increase in urinary pH and bicarbonate levels
      found in urine collected from 20 students who stayed in a cinema for 3 h, at
      which location carbon dioxide levels in air reached 1 200 ppm.

PMID- 8572726
TI  - An individual with a majority of ferruginous bodies formed on chrysotile cores.
AB  - A 59-year-old man was exposed to chrysotile asbestos while rebuilding clutches.
      Analytical electron microscopy showed a chrysotile core in 72% of the ferruginous
      bodies from lung tissue. Long, uncoated chrysotile fibers were also present.
      Sufficient exposure to long chrysotile in jobs such as this appears to allow the
      majority of ferruginous bodies to be formed on chrysotile, an exception to the
      rule that most ferruginous bodies form on amphibole cores.

PMID- 8572727
TI  - Tendon lesions and soft tissue rheumatism--great outback or great opportunity?

PMID- 8572728
TI  - Not all stoops are due to osteoporosis.

PMID- 8572729
TI  - Association of hand and knee osteoarthritis: evidence for a polyarticular disease
      subset.
AB  - OBJECTIVE: To examine the association between hand and knee osteoarthritis (OA)
      in a community based population. METHODS: Radiographs of 695 participants aged >
      or = 40 years in the Baltimore Longitudinal Study of Aging were read for changes
      of OA, using Kellgren-Lawrence grade > or = 2 as the case definition. RESULTS:
      Logistic regression analyses, adjusting for age, gender and body mass index,
      revealed a significant association between OA in the knee and the following joint
      groups: distal and proximal interphalangeal (DIP, PIP) and Hand2 (OA in two or
      more hand joint groups) for grade 2-4 and grade 3-4 disease, and the first
      carpometacarpal (CMC1) joint for grade 3-4 disease. CONCLUSION: There is an
      association between OA in hand sites and the knee. The strength of the
      associations increases with increasing disease severity. For the PIP site, there
      is a trend toward increasing strength of association for increasing numbers of
      affected joints and bilateral disease.

PMID- 8572730
TI  - Analysis of the association between chondrocalcinosis and osteoarthritis: a
      community based study.
AB  - OBJECTIVES: To analyse the association between chondrocalcinosis and
      osteoarthritis (OA) of the hands and knees in an unselected elderly rural
      population. METHODS: A community based cross sectional study was performed in
      individuals randomly selected from a previous epidemiological survey on the
      prevalence of chondrocalcinosis in people older than 60 years from Osona county,
      Catalonia, northeastern Spain. Radiological OA (grade 2 or more of Kellgren's
      classification) was evaluated in 26 individuals with chondrocalcinosis and in 104
      controls. A total of 18 articular areas of both knees (medial and lateral
      tibiofemoral compartments) and hands (first, second and third metacarpophalangeal
      (MCP), first carpometacarpal, trapezium-scaphoid, radiocarpal and distal
      radioulnar joints) were studied. RESULTS: Radiological changes of OA in the knees
      were more common in subjects with chondrocalcinosis than in those without it,
      with an odds ratio adjusted for age and gender (aOR) of 4.3 (95% confidence
      interval (CI) 1.6 to 11.8, p = 0.005). OA was also more frequent in almost all
      areas of the hands in individuals with chondrocalcinosis, though the difference
      reached statistical significance only in the MCP joints (aOR 3.1; 95% CI 1.1 to
      8.8; p = 0.033). However, taking into account the side and the different joint
      compartments analysed, the association between chondrocalcinosis and OA was
      significant only in the lateral tibiofemoral compartment and the left MCP joints.
      CONCLUSIONS: In an elderly population unselected for their rheumatic complaints,
      there was a real association between OA and chondrocalcinosis. This association
      was particularly relevant in the lateral tibiofemoral compartment of the knee and
      in the first three left MCP joints.

PMID- 8572732
TI  - The language of rheumatology. I: Nomenclature and coding.

PMID- 8572731
TI  - Associations of HLA-DRB and -DQB genes with two and five year outcome in
      rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the clinical usefulness of genomic HLA typing during the
      first five years of established rheumatoid arthritis (RA). METHODS: The HLA-DRB
      and -DQB alleles were determined by restriction length polymorphisms and
      polymerase chain reaction amplification with sequence specific primers in 99
      Swedish patients with RA. Clinical features after two and five years disease
      duration were related to the genetic pattern. Seventy four patients were
      seropositive, 25 had nodules, 90 developed erosions, and 15 required joint
      replacements. Twelve patients were in remission after five years. Disability was
      assessed by health assessment questionnaire, and radiographic damage in hands and
      feet by the Larsen method. RESULTS: Eighty seven per cent of the patients carried
      the conserved third hypervariable region sequence (HVR3), 32% had DRB1*04 on one
      allele, and 26% had DRB1*04 on both alleles (all frequencies significantly
      greater than in controls). Frequencies of DRB1*04 associated DQB*0301 and *0302
      were normal. Patients carrying DRB1*04 on both alleles tended to have more
      radiographic changes after two years, but this difference had diminished after
      five years. Disability did not vary with regard to the genotype. Homozygous HVR3
      patients had about three times greater risk of undergoing joint replacement.
      Homozygosity for HVR3 and presence of DQB*0302 both tended to be associated with
      erosive disease. CONCLUSIONS: We confirmed a strong association of disease with
      the presence of the shared epitope on one or two alleles. However, genotype was
      not strongly associated with disease severity after two and five years disease
      duration, and thus the value of genomic typing to select patients for early
      aggressive therapy is questionable.

PMID- 8572733
TI  - Cellular immunity to cartilage aggrecan core protein in patients with rheumatoid
      arthritis and non-arthritic controls.
AB  - OBJECTIVE: To identify antigen(s) among purified deglycosylated aggrecan peptides
      spanning the chondroitin sulphate domain that may be responsible for the
      initiation or perpetuation of the autoimmune responses in rheumatoid arthritis
      (RA). METHODS: Aggrecan was purified from human articular cartilage and
      deglycosylated with either bacterial glycosidases or trifluoromethanesulphonic
      acid (TFMS). Twelve overlapping peptides (15 residues) spanning the chondroitin
      sulphate domain with N-terminal residues offset by three amino acids were
      synthesised. T cell responses to these antigens in RA patients and age matched
      controls were assessed in vitro by antigen specific T cell proliferation assays.
      RESULTS: Enzymically deglycosylated aggrecan (EDA) stimulated proliferation of T
      cells isolated from the peripheral blood in a greater proportion of patients with
      RA than controls. In a subset (12.5%) of RA patients, the magnitude of
      stimulation lay outside the control range. T cell proliferative responses to TFMS
      treated aggrecan were greater than, but well correlated with, responses to EDA. T
      cells from 15 patients were also stimulated with the pooled synthetic peptides.
      Four of seven patients who demonstrated T cell reactivity to EDA (seven of 15)
      also showed enhanced T cell proliferation to synthetic peptides. CONCLUSION:
      These data suggest that an autoantigenic T cell epitope may lie within the
      chondroitin sulphate domain of aggrecan.

PMID- 8572734
TI  - Synovial fluid and serum concentrations of aminoterminal propeptide of type III
      procollagen in healthy volunteers and patients with joint disease.
AB  - OBJECTIVES: To analyse synovial fluid and serum concentrations of the amino
      propeptide of the type III procollagen (PIIINP) in normal individuals and
      patients with joint disease, and to explore the relationship between synovial
      fluid PIIINP concentrations and the rheumatological diagnosis, local
      inflammation, and joint disease. METHODS: A radioimmunoassay was used to measure
      the PIIINP concentrations in serum and knee joint synovial fluid from 16 healthy
      volunteers and patients with osteoarthritis (OA) (n = 40), rheumatoid arthritis
      (RA) (n = 30), and psoriatic arthritis (PsA) (n = 12). The PIIINP measurements
      were related to demographic data, synovial fluid leucocyte counts, and
      radiographic changes at the knee. RESULTS: Serum PIIINP concentrations were
      greater in each of the disease groups than in control subjects, but there were no
      differences between the disease groups. Synovial fluid concentrations of PIIINP
      were much greater than those in serum, indicating local production, and were
      significantly greater in RA than in other disease groups (p < 0.001). There was
      only a weak positive correlation between synovial fluid leucocyte counts, some
      radiographic changes, and synovial fluid PIIINP concentrations. CONCLUSIONS:
      These data suggest that synovial fluid PIIINP concentrations may reflect local
      synovial proliferative processes in joint disease, and that they could be of
      diagnostic and prognostic value in inflammatory arthropathies.

PMID- 8572735
TI  - Computer based quantitative analysis of capillary abnormalities in systemic
      sclerosis and its relation to plasma concentration of von Willebrand factor.
AB  - OBJECTIVES: To evaluate an objective and quantitative method for assessment of
      capillary abnormalities in systemic sclerosis (SSc). METHODS: Nailfold
      capillaries were investigated by capillary microscopy and photographed in 17
      consecutive SSc patients (five with diffuse cutaneous systemic sclerosis (dSSc)
      and 12 with limited cutaneous systemic sclerosis (lSSc)) and in 17 healthy
      controls. Investigators having no access to clinical data made drawings from
      magnified projections of coded photographs and analysed them using a computer
      program. Capillary density (capillary loops/mm in the distal row) and median
      capillary loop area were calculated. Presence of functional or organic arterial
      changes was evaluated by measurement of finger pressure with finger cooling.
      Plasma concentration of von Willebrand factor (VWF) was analysed using an enzyme
      linked immunosorbent assay (ELISA). RESULTS: In 16 of 17 SSc patients and 13 of
      17 controls the technical quality of the photographs was sufficient for computer
      analysis. Capillary density was decreased in dSSc (median 6.9 loops/mm) and in
      lSSc (median 3.8 loops/mm) compared with healthy controls (8.9 loops/mm) and
      median capillary loop area was increased in dSSc (7.3 x 10(-3) mm2) and in lSSc
      (8.5 x 10(-3) mm2) compared with healthy controls (5.0 x 10(-3) mm2). An inverse
      relation was found between capillary density and median capillary loop area in
      SSc patients. Plasma VWF was increased in patients (median 401 IE/l in dSSc and
      409 IE/l in lSSc) compared with controls matched for age and sex (median 276
      IE/l). Computer based analysis showed capillary density below the control range
      and median capillary loop area above the control range in 14 of 16 SSc patients.
      Measurement of finger pressure with finger cooling showed organic vascular
      changes in nine of 13 SSc patients. CONCLUSION: Computer based quantitative
      analysis has low interobserver variability and is a quantitative and sensitive
      method of assessing capillary abnormalities in SSc.

PMID- 8572736
TI  - Increased release of von Willebrand factor antigen from endothelial cells by anti
      DNA autoantibodies.
AB  - OBJECTIVE: To determine whether antibodies to double stranded DNA (anti-dsDNA)
      have a pathogenic role in systemic lupus erythematosus (SLE). METHODS: IgG was
      purified from 17 patients with SLE (median anti-dsDNA titre 1212 IU/ml) and nine
      healthy controls (median titre 40 IU/ml). Anti-dsDNA depleted polyclonal IgG
      (median anti-dsDNA titre 17 IU/ml) was also prepared from sera of the 17 patients
      by affinity chromatography on a DNA cellulose column. Binding to antiendothelial
      cell antibodies (AECA) and expression of von Willebrand factor (VWF) antigen by
      cultured human umbilical vein endothelial cells (HUVECs) were studied by flow
      cytometry. RESULTS: The percentage of HUVECs binding to AECA or expressing VWF
      was greater for cells incubated with IgG from patients with SLE than for cells
      incubated with control IgG, though values did not reach statistical significance;
      nevertheless, HUVECs incubated with IgG from patients expressed a greater mean
      fluorescence intensity with AECA (p = 0.0001) and greater VWF expression (p =
      0.019). Both the fluorescence intensity and percentage of HUVECs binding to AECA
      or expressing VWF were significantly greater in HUVEC incubated with IgG
      containing anti-dsDNA than in those incubated with anti-dsDNA depleted IgG. The
      concentration of VWF in the supernatant was significantly increased in HUVECs
      incubated with IgG containing anti-dsDNA compared with control IgG or anti-dsDNA
      depleted IgG. Pretreatment of HUVECs with native DNA before incubation with IgG
      from lupus patients did not increase binding to AECA, or expression or release of
      VWF. CONCLUSIONS: Our study provides in vitro evidence that antibodies to DNA
      have a pathogenic role in the induction of inflammatory injury of the vascular
      endothelium in SLE.

PMID- 8572737
TI  - Effect of HLA type and hypocomplementaemia on the expression of parvovirus
      arthritis: one year follow up of an outbreak.
AB  - OBJECTIVES: To determine the effect of HLA type and hypocomplementaemia on the
      duration and severity of joint involvement in parvovirus infection (HPV).
      METHODS: Forty seven patients were selected on a geographical basis from 83 with
      proven HPV infection during an outbreak that occurred in Oxfordshire in 1993.
      They were contacted by questionnaire a year later. Thirty five patients were
      available for examination and blood sampling. Subjects were typed for HLA-DRB1
      alleles and HLA-B27 status. Immunological profiles, including C3 and C4
      complement components, were determined. RESULTS: Joint symptoms occurred in all
      patients. They resolved within a week in 12 patients and persisted beyond one
      year in 19. On review, none had a picture of rheumatoid arthritis, but three
      patients had developed carpal tunnel syndrome. Decreased C4 was found in four.
      The HLA frequencies were similar to those in controls; however, joint symptoms
      persisted for more than one week in all HLA-DR4 positive patients (p = 0.009).
      There was no relation between the severity of joint symptoms and either HLA type,
      or hypocomplementaemia. CONCLUSIONS: Joint symptoms are common in parvovirus
      infection and the presence of HLA-DR4 may be associated with persistence of joint
      symptoms beyond one week. This study revealed no evidence of progression to
      rheumatoid arthritis.

PMID- 8572738
TI  - Relationship between genotype for the cytochrome P450 CYP2D6 and susceptibility
      to ankylosing spondylitis and rheumatoid arthritis.
AB  - OBJECTIVES: To determine whether particular genotypes for the cytochrome P450
      enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to
      ankylosing spondylitis (AS) and rheumatoid arthritis (RA), or linked with any
      specific clinical or familial features of the two conditions. METHODS: CYP2D6
      genotypes were determined in 54 patients with AS, 53 patients with RA, and 662
      healthy controls. Leucocyte DNA was analysed for the presence of mutations by
      restriction fragment length polymorphism analysis with the restriction enzyme
      Xbal and by two separate polymerase chain reaction assays. RESULTS: On the basis
      of odds ratio (OR), individuals with two inactive CYP2D6 alleles were more
      susceptible to AS than controls (OR 2.71, 95% confidence interval (CI) 1.04 to
      7.08), with a stronger effect for the CYP2D6B allele (OR 4.11, 95% CI 1.54 to
      11.0). No significant differences in the distribution of overall genotypes and
      allele frequencies were observed between RA and controls. No significant
      relationships were found between the skeletal, extraskeletal or familial features
      of AS or RA (iritis, psoriasis, inflammatory enteropathy and rheumatoid nodules,
      kerato-conjunctivitis sicca, pleuritis, rheumatoid and antinuclear factors) and
      the overall genotype. CONCLUSIONS: Our findings suggest a modest association
      between homozygosity for inactive CYP2D6 alleles, particularly CYP2D6B alleles,
      and susceptibility to AS. However, our results fail to demonstrate a genetic link
      between CYP2D6 genotype and RA.

PMID- 8572739
TI  - Expression of rheumatoid arthritis in two ethnic Jewish Israeli groups.
AB  - OBJECTIVE: To investigate the expression of rheumatoid arthritis (RA) in Jewish
      Israeli patients according to ethnic origin. METHODS: RA patients who were seen
      in a primary public rheumatology clinic were divided into two groups according to
      ethnic origin (Sepharadic or Askenazi) and subjected to a cross sectional study.
      The two groups were compared for history, physical status, and radiographic and
      laboratory variables. The entire study population was again divided into two
      groups according to formal educational level, and these were also compared for
      the same variables as above. RESULTS: The patients of Sepharadic origin had
      significantly more pathological recordings of pain and fatigue, and greater
      Ritchie scores than those of Askenazi origin. The Sepharadic group patients were
      younger, had a lower educational level, and were predominantly female. The more
      educated group recorded significantly less pathological pain and fatigue, and had
      smaller Ritchie scores. Functional capacity and global disease severity, assessed
      by physician and patient, were also reduced in the more educated group. On
      multiple regression analysis, ethnic origin was found to be independently related
      to functional class. Education was found to be independently related to the
      Ritchie score. CONCLUSIONS: Disease manifestations in Jewish RA patients of
      Sepharadic origin are more serious compared with those in patients of Askenazi
      origin. In addition, low educational level is related to more severe disease
      manifestations in Israeli RA patients.

PMID- 8572742
TI  - Commented glossary for rheumatic spinal diseases.

PMID- 8572741
TI  - Redundancy of conventional articular response variables used in juvenile chronic
      arthritis clinical trials.
AB  - OBJECTIVE: To estimate the degree of redundancy among articular response
      variables used routinely in juvenile chronic arthritis (JCA) clinical trials.
      METHODS: We obtained data from a large, computerised databank holding information
      from multiple clinical trials in children with JCA to determine Pearson
      correlation coefficients for changes from baseline values in articular response
      variables. All 508 JCA patients who entered the analysis of efficacy of the
      original trials were included in the present study. An r value of 0.7 or greater
      was considered evidence of colinearity. RESULTS: When changes in joint counts of
      articular manifestations were compared with changes in the respective severity
      scores (for example swollen joint count versus swelling severity score), the r
      values were always > or = 0.7. Three articular response variables related to the
      assessment of pain are all highly correlated with each other. The number of
      joints with active arthritis was correlated with the number of joints with
      swelling and the swelling score. Change in the overall severity score was highly
      correlated (r > or = 0.7) with change in nearly all articular response variables.
      CONCLUSIONS: Many endpoints reported in JCA trials are redundant, especially
      counts and scores of the same articular measure. Eliminating redundant variables
      would provide the same information with less complexity, and decrease the
      probability of statistical error and ambiguous results.

PMID- 8572743
TI  - Commented glossary for rheumatic spinal diseases.

PMID- 8572744
TI  - Commented glossary for rheumatic spinal diseases.

PMID- 8572740
TI  - Nitric oxide.

PMID- 8572745
TI  - Destructive large joint arthritis.

PMID- 8572746
TI  - [Apprenticeship in adult education. The case of education of general
      practitioners].

PMID- 8572747
TI  - [The general practitioner on the first step in the Third World].

PMID- 8572748
TI  - [The general practitioner in the hospital: from routine activities to a practice
      which energizes the health district].

PMID- 8572749
TI  - Change in undergraduate medical education.
AB  - Undergraduate medical education didn't undergo major changes since the Flexner
      report in the beginning of this century and has since been copied without
      important modifications worldwide. The bulk of the medical education is given by
      subject specialists and general practice is only marginally covered. The result
      is that the training of medical doctors has become inappropriate and that a
      change is urgently needed. The aim is on the one hand to improve the clinical
      skills of doctors, on the other hand to prepare doctors for enhanced roles and to
      have some community perspective. Innovations such as problem-based learning and
      community-oriented education took mainly place in new medical schools. The need
      to change medical education is however greater in established medical schools,
      but innovation seems more difficult to reach there, although some successful
      experiences are described. Most innovations failed to tackle reform of the health
      system in which new graduates will function. This is probably one of the main
      reasons for their limited results. Five presentations to the Colloquium
      illustrate the difficulties and possible successes of change in undergraduate
      medical education.

PMID- 8572750
TI  - Clinical training for tropical doctors in the nineties.
AB  - Together with economic causes, the declining belief in the relevance of clinical
      skills, the omission of the hospital from the health system, and the erroneous
      generalisation of a complaint centred approach enhanced the decline in clinical
      medicine in several developing countries over the last decades. Despite a growing
      interest and important efforts in continuous education, basic training remains
      generally knowledge-directed. Clinical training should start from a realistic job
      description, and aim at acquiring skills instead of knowledge. Basics of clinical
      epidemiology can help refine clinical logic both at the health centre and the
      hospital level. the district hospital should be awarded a key role in pre
      graduate and continuous clinical training. Awaiting a revival of the economy in
      most tropical countries, and especially in tropical Africa, an effective way for
      improving clinical practice is to invest in training, at all levels, with an
      emphasis on continuous medical training.

PMID- 8572751
TI  - [What to expect of an improvement in education of general practitioners in
      developing countries?].

PMID- 8572752
TI  - Roles of the general practitioner in different contexts.
AB  - The word ?general practice? denotes different contents of work as we look at
      different contexts. General practitioners may provide first line care, function
      as secondary care providers at hospital level, take responsibility for the
      management of health care systems. These different roles can be seen as results
      from historical processes of division of work in the field of health care, which
      gave general practice its present shapes. During the first half of the 20th
      century, western general practitioners were gradually excluded from hospitals as
      well as from public health activities. When they started to react in order to
      increase their legitimacy they strived--with variable success--to gain
      recognition as curative first line care providers, as this had become the only
      place in the health care system they could claim for. They gradually defined
      their specificity in terms of polyvalence enabling them to deal with unselected
      problems, and in terms of global view allowing for adequate priority setting. In
      developing countries, the organisation of medical care was and remains influenced
      by western models. As in western countries, emphasis has been put on
      specialisation and hospital technology. General practice was not exported to
      developing countries: general practitioners appear rather as cheap substitutes
      for specialists. The most typical workplace for general practitioners in
      developing countries remains the rural hospital. But their role model refers to
      the hospital based specialist: they tend to focus on patient care for hospital
      users rather than on dynamising health care delivery to the whole community in
      the district. In urban areas, the recent expansion of (mostly private) first line
      medical care is also not specific to general practice and tends to be in favour
      of specialists. What is the common denominator to these different roles, if any?
      A possible answer lies in the primary health care approach. It allows to define
      the specificity of general practitioners in terms of multifactorial approach and
      global view on health and illness, which differentiates them from specialists.
      Whether they provide this care themselves or organise it at district level could
      be less important to their professional identity than the general attitudes and
      knowledge they rely on.

PMID- 8572753
TI  - [Role of education in the development of health systems].

PMID- 8572754
TI  - The bright future of cardiothoracic surgery in the era of changing healthcare
      delivery.
AB  - We are currently at a crossroads in our specialty and in the American healthcare
      delivery system. The manner in which we approach the next 5 to 10 years will
      deeply affect the future of our specialty. Thoracic surgery has had many
      accomplishments during my 35-year career that have improved the healthcare for
      the American public and others. As cardiothoracic surgeons, we have a legacy to
      be proud of, and the future promises to be every bit as exciting. In spite of
      these tremendous advances and the potential for future scientific achievements,
      there has been considerable uncertainty and pessimism because of the changing
      structure of healthcare in the United States. This has largely been stimulated by
      increasing health-care expenditures leading to the development of health
      maintenance organizations in the hopes of curtailing expenses by competition and
      capitation. In addition to cost containment, managed care is likely to have an
      impact on the future workforce of cardiothoracic surgeons. Much of our future
      will be determined by how well we adapt to the changing environment and take
      charge of our destiny. The demand for performance information for managed care
      plans will be much greater than it has been in the past. It is, therefore,
      imperative that we collect data to reflect the quality and value of our work to
      ensure that significant quality is not being sacrificed for cost containment. We
      cardiothoracic surgeons must develop our own information management strategies so
      that we can be in control of our future. If we do this, I am confident that the
      future of cardiothoracic surgery will be a bright one indeed.

PMID- 8572755
TI  - In celebration of STSA training programs, 1995: University of Texas Health
      Science Center, San Antonio, Texas.

PMID- 8572756
TI  - A randomized study would answer the question.

PMID- 8572757
TI  - Obliteration of the left atrial appendage: a concept worth testing.

PMID- 8572758
TI  - Value of perioperative Doppler echocardiography in patients undergoing major lung
      resection.
AB  - BACKGROUND: The effects of major lung resection on right heart function have not
      been well established. Our goal was to evaluate these effects using serial
      Doppler echocardiography in the perioperative period. METHODS: In 86 patients
      undergoing lobectomy (n = 47) and pneumonectomy (n = 39), we examined the effects
      of pulmonary resection on perioperative changes in right heart function by
      transthoracic echocardiography. Serial echocardiograms were performed
      preoperatively, on postoperative day 1, and again between postoperative days 2
      and 6 (median, 3 days) to evaluate cardiovascular function and to estimate right
      ventricular systolic pressure by the tricuspid regurgitation jet Doppler velocity
      method. RESULTS: Right or left atrial size, right atrial pressure, and estimated
      right ventricular systolic pressure did not differ between groups on the
      preoperative or postoperative day 1 examinations. However, on postoperative days
      2 through 6 patients who underwent pneumonectomy had higher (mean +/- standard
      deviation) right ventricular systolic pressure values than lobectomy patients (31
      +/- 15 versus 25 +/- 10 mm Hg, respectively; p < 0.05 by analysis of variance).
      In the subset of patients with percent predicted forced expiratory volume in 1
      second less than 60% undergoing pneumonectomy (9/39), preoperative right
      ventricular systolic pressure was inversely correlated with percent predicted
      forced expiratory volume in 1 second values (r = -0.78; p < 0.04). This
      correlation was not significant in corresponding lobectomy patients.
      Postoperative right ventricular enlargement determined by echocardiography
      occurred with similar frequency in both groups and was associated with poor short
      term prognosis in patients in whom severe respiratory failure developed.
      CONCLUSIONS: Preoperative indices of right heart function were within the normal
      range in both groups. Pneumonectomy but not lobectomy was associated with mild
      postoperative pulmonary hypertension that was not accompanied by significant
      right ventricular systolic dysfunction. Postoperative echocardiography may be
      useful to evaluate right heart function in critically ill patients after lung
      resection.

PMID- 8572759
TI  - Surgical treatment for invasive thymoma, especially when the superior vena cava
      is invaded.
AB  - BACKGROUND: We analyzed the operative outcome of extensive surgery for invasive
      thymoma, especially in those with thymomas invading the superior vena cava, the
      left innominate vein, or both. METHODS: We treated 41 patients with invasive
      thymoma, including 34 stage III, 5 stage IVa, and 2 stage IVb thymomas. Thirty
      eight patients received radiotherapy preoperatively or postoperatively. In 12
      patients with invasion of the superior vena cava or innominate vein, we performed
      angioplasty, reconstruction, or both. RESULTS: The overall 5-year survival rate
      was 77% and the 10-year survival rate was 59%. In the stage III group, there was
      a significant difference between those with complete and those with incomplete
      resection. Ten of 12 patients who had angioplasty with or without reconstruction
      of the superior vena cava or innominate vein survived without recurrence of the
      tumors. CONCLUSION: Angioplasty and vascular reconstruction are recommended
      because successful treatment for invasive thymomas depends on complete resection
      of the tumors.

PMID- 8572760
TI  - Bone heterograft for chest wall reconstruction after sternal resection.
AB  - BACKGROUND: Experimental and clinical results of chest-wall reconstruction with
      bone heterograft after sternectomy are reported. METHODS: Seven dogs underwent
      subtotal or total sternectomy and reconstruction by implantation of a cortico
      spongy bone heterograft sandwiched between two layers of a reabsorbable mesh.
      RESULTS: No major postoperative complications were observed. The implant has
      shown favorable mechanical and biological properties. Six and 9 months after
      operation all animals were sacrificed and pathologic examination showed good
      incorporation of the implanted bone with only partial resorption of its
      spongiosa. Subsequently, 2 patients underwent sternal resection with different
      indications and reconstruction was achieved by the technique developed
      experimentally. No complications were observed. Excellent immediate chest-wall
      stabilization was obtained, persisting for a follow-up period longer than 6
      months. CONCLUSIONS: In comparison with autologous bone, sterile bone heterograft
      seems to offer the same mechanical properties with a significantly reduced
      surgical trauma.

PMID- 8572761
TI  - Should cavitated bronchopulmonary cancers be considered a separate entity?
AB  - BACKGROUND: This study was designed to identify any clinical, histologic, and
      prognostic features specific to cavitated bronchopulmonary tumors. METHODS: A
      total of 353 patients with lung cancer were categorized in two groups on the
      basis of chest radiograph and computed tomographic findings: 35 patients with
      cavitated cancers (group I) and 318 patients with noncavitated neoplasms (group
      II). Cavitation was defined as the presence of air in the tumor at the time of
      diagnosis and before any treatment or aspiration biopsy. The two groups were
      compared. RESULTS: There was no significant difference between the two groups
      concerning age, smoking history, or the interval to diagnosis, but diabetes
      (14.3% versus 5%) and fever (28.6% versus 13.5%) were significantly more frequent
      in group I than in group II. No statistically significant difference was observed
      between the two groups in tumor site or endoscopic appearance. Cavitated tumors
      were 1.5 times larger than the noncavitated lesions. Squamous cell carcinoma was
      significantly more frequent in group I than in group II (82.8% versus 61%).
      Survival at 1, 3, and 5 years was, respectively, 58.6%, 36.1%, and 22.2% in group
      I versus 48.2%, 35%, and 23.8% in group II. CONCLUSIONS: Despite several specific
      features, there appears to be no justification for considering cavitated
      neoplasms separately from other forms of lung cancer.

PMID- 8572762
TI  - Complications of video-assisted thoracic surgery: a five-year experience.
AB  - BACKGROUND: Although thoracoscopy was originally described in 1910, recent
      developments in video-assisted surgical techniques and endoscopic equipment has
      expanded the application of video-assisted surgical procedures in the field of
      thoracic surgery. METHODS: In an effort to define both high-risk patients for
      video-assisted thoracic procedures and high-risk video-assisted thoracic surgical
      procedures, we reviewed the experience of four surgical institutions from June
      1991 through May 1995. We looked specifically at complications resulting from the
      937 video-assisted thoracic procedures performed during this period. RESULTS:
      Perioperative incidents or complications occurred in 35 patients (3.7%), and 116
      procedures (12.4%) were converted to a thoracotomy. The in-hospital mortality
      rate was 0.5%, and death occurred principally in patients operated on for
      malignant pleural effusion. The overall incidence of postoperative complications
      was 10.9%, and the most prevalent complications were prolonged air leak (6.7%)
      and pleural effusion (0.7%). CONCLUSIONS: The incidence of complications was
      acceptable and, except for that of prolonged air leak, did not differ
      significantly from that resulting from analogous open procedures. Video-assisted
      thoracic surgery appears safe and particularly useful for some indications.
      However, the possibility of dramatic life-threatening perioperative complications
      requiring emergency conversion to thoracotomy justifies the fact that only
      trained thoracic surgeons should perform video-assisted thoracic surgical
      procedures.

PMID- 8572763
TI  - Complications and failures of video-assisted thoracic surgery: experience from
      two centers in Asia.
AB  - BACKGROUND: There have been few specific reports on negative outcomes after video
      assisted thoracic surgery. We report our combined experience from two centers in
      Asia. METHODS: From September 1992 to April 1995, 1,337 patients were operated on
      with the video-assisted thoracic surgical approach. All the patients were
      prospectively studied. RESULTS: There was one death (mortality rate, 0.07%) and
      56 nonfatal complications: persistent air leaks (21), bleeding (6), wound
      infection (13), empyema (2), cerebrovascular accident (1), reexpansion pulmonary
      edema (2), deep vein thrombosis (1), prolonged ventilatory support (4),
      intercostal neuralgia (5), and port-site recurrence (1), giving rise to an
      overall nonfatal complication rate of 4.26%. Procedure failures consisted of 7
      recurrences of spontaneous pneumothorax (of 407 cases or 1.7%); 2 recurrences of
      malignant pleural effusion (of 39 cases or 5.1%), and 2 local recurrences after
      resections for stage I lung cancers (of 41 cases or 4.9%). CONCLUSIONS: We
      conclude that video-assisted thoracic surgery is safe and effective for a wide
      range of procedures. A learning curve is present, and careful patient selection
      and attention to details are essential in optimizing surgical results.

PMID- 8572764
TI  - Trehalose-containing solutions enhance preservation of cultured endothelial
      cells.
AB  - BACKGROUND AND METHODS: We have developed two types of preservation solutions
      containing trehalose. ET-Kyoto solution (ET-K) is an extracellular type and IT
      Kyoto solution (IT-K) is an intracellular type. In the present study we examined
      with in vitro assays the ability of ET-K, IT-K, Euro-Collins (EC), and University
      of Wisconsin (UW) solutions to preserve a murine endothelial cell line. The
      viability of cells stored in the solutions at 4 degrees C was determined by
      trypan blue exclusion and MTT assay. RESULTS: Trypan blue exclusion showed the
      viability after 48 hours of cold storage to be 49.5 +/- 4.7% (mean +/- standard
      error) in ET-K, 59.5 +/- 0.7% in IT-K, 29.2 +/- 2.5% in EC, and 55.3 +/- 7.6% in
      UW (ET-K or UW versus EC, p < 0.05; IT-K versus EC, p < 0.01). MTT assay
      absorbance values for cells after 48 hours of cold storage were 0.366 +/- 0.0066
      (mean +/- standard error) in ET-K, 0.358 +/- 0.0044 in IT-K, 0.336 +/- 0.011 in
      EC, and 0.362 +/- 0.0019 in UW (ET-K or UW versus EC, p < 0.05). After 120 hours,
      absorbance values for cells were 0.303 +/- 0.0038 in ET-K, 0.269 +/- 0.0034 in IT
      K, 0.186 +/- 0.011 in EC, and 0.265 +/- 0.0066 in UW (ET-K versus UW, p < 0.05;
      ET-K versus IT-K, p < 0.01; ET-K, IT-K or UW versus EC, p < 0.01). CONCLUSIONS:
      As far as the ability to preserve a murine endothelial cell line at a low
      temperature was concerned, the ET-K solution was superior to the UW solution, the
      IT-K solution and UW solution were equal, and the ET-K and IT-K solutions were
      superior to the EC solution.

PMID- 8572765
TI  - Brain metastasis in resected lung cancer: value of intensive follow-up with
      computed tomography.
AB  - BACKGROUND: Brain metastases are a common mode of recurrence in resected lung
      cancer and are usually associated with an ominous outcome. METHODS: To assess the
      usefulness of follow-up using computed tomography of the brain for early
      detection and effective treatment of brain metastases, we prospectively studied
      128 patients with completely resected non-small cell lung cancer. Follow-up
      computed tomographic scans were obtained every 2 to 6 months over 24
      postoperative months in 69 patients and every 2 months for 6 postoperative months
      in 59. RESULTS: Brain metastases were discovered in 11 patients (8.6%), and 7
      patients were neurologically asymptomatic when the metastases were diagnosed.
      Single metastasis was found in 5 patients and multiple metastases in 6. The
      maximal size of all but one lesion was less than 25 mm. The median survival time
      and 5-year survival rate in all 11 patients with brain metastases were 10 months
      and 24%, respectively. Furthermore, those in 7 asymptomatic patients were 25
      months and 38%, respectively. CONCLUSIONS: We consider intensive follow-up with
      computed tomography to be worthwhile for early detection and effective treatment
      of brain metastases in patients with completely resected lung cancer.

PMID- 8572766
TI  - Can patients with left main stenosis wait for coronary artery bypass grafting?
AB  - BACKGROUND: The economic impact of health care reforms may result in waiting
      lists for coronary artery bypass grafting. This study was designed to examine the
      clinical results of patients with left main stenosis who were placed on a triaged
      wait list for operation. METHODS: Data were collected prospectively on 2,145
      patients undergoing isolated coronary artery bypass grafting between 1989 and
      1994. Critical left main stenosis (LMS, 50% or more stenosis) was present in 281
      patients, and 1,864 patients had no left main disease, or a left main stenosis of
      less than 50% (no LMS). RESULTS: The average time from angiography to operation
      was shorter in patients with LMS (LMS 38 +/- 46 days versus no LMS 84 +/- 71
      days; p = 0.0001). Two patients in the LMS group died; they had declined
      operation. Four patients suffered non-Q wave myocardial infarctions, all of whom
      subsequently underwent operation with no perioperative complications. The
      presence of LMS did not influence operative mortality (LMS 2.8% versus no LMS
      1.3%), the incidence of low output syndrome (LMS 8.3% versus no LMS 5.4%), or the
      incidence of perioperative myocardial infarction (LMS 3.8% versus no LMS 4.2%).
      To examine the effect of waiting time on outcomes, patients with LMS were divided
      into early (operation 10 days or less after angiography) and late
      revascularization groups (more than 10 days). Operative mortality, low output
      syndrome, and myocardial infarction were similar in the early and late groups.
      Patients in the early group were more likely to have New York Heart Association
      functional class IV symptoms (64% versus late 22%; p < 0.0001), unstable angina
      (87% versus late 65%; p < 0.0001), or a recent preoperative myocardial infarction
      (17% versus late 2%; p < 0.0001). CONCLUSIONS: Carefully selected patients with
      significant left main stenosis can safely wait for operation with a low risk of
      complications. Early surgical intervention is allocated to patients with severe
      symptoms or recent preoperative myocardial infarction.

PMID- 8572767
TI  - Beneficial effects of myocyte preconditioning on contractile processes after
      cardioplegic arrest.
AB  - BACKGROUND: Myocardial precondition, which can be achieved through short
      intervals of ischemia or hypoxia followed by reperfusion, protects the myocardium
      with subsequent prolonged periods of ischemia. Accordingly, the present study
      tested the hypothesis that hypoxic preconditioning before cardioplegic arrest
      would have direct and beneficial effects on myocyte contractile processes with
      reperfusion. METHODS: Left ventricular porcine myocytes (n = 335) were randomly
      assigned to one of three treatments: normothermia, maintained in cell media (37
      degrees C, 2 hours); cardioplegia, hyperkalemic arrest (24 mEq K+, 4 degrees C, 2
      hours) followed by normothermic reperfusion; preconditioning, hypoxia (20
      minutes) and reperfusion (20 minutes), and then followed by cardioplegic arrest
      and rewarming. Myocyte velocity of shortening was measured using computer
      assisted videomicroscopy at baseline and with beta-adrenergic receptor
      stimulation with isoproterenol (25 nmol/L). RESULTS: In the cardioplegia group,
      myocyte function was reduced at baseline (22 +/- 1 versus 57 +/- 2 microns/s) and
      with beta-adrenergic receptor stimulation (81 +/- 5 versus 156 +/- 7 microns/s)
      compared to normothermic controls (p < 0.05). Preconditioning improved myocyte
      function at baseline (38 +/- 2 microns/s) and with beta-adrenergic receptor
      stimulation (130 +/- 6 microns/s) compared to the cardioplegic alone group (p <
      0.05). CONCLUSIONS: The important findings from this study are twofold. First,
      preconditioning can be induced directly at the level of the myocyte, independent
      of nonmyocyte populations and extracellular influences. Second, myocyte
      preconditioning provides protective effects on myocyte function and beta
      adrenergic responsiveness after cardioplegic arrest and rewarming. These findings
      suggest that preconditioning may provide a novel approach in protecting myocyte
      contractile processes during cardioplegic arrest.

PMID- 8572768
TI  - Thoracoscopic obliteration of the left atrial appendage: potential for stroke
      reduction?
AB  - BACKGROUND: In a review of all relevant articles describing the site of left
      atrial thrombus in patients with atrial fibrillation, the thrombus was localized
      to the left atrial appendage in 43% of patients with rheumatic heart disease and
      in 91% of patients with nonrheumatic atrial fibrillation. This study was designed
      to test the feasibility of thoracoscopic obliteration of the left atrial
      appendage as a means of reducing thromboembolic stroke. METHODS: Thoracoscopic
      obliteration of the left atrial appendage was undertaken in 10 dogs, 5 with
      staples and 5 with an endoloop. Obliteration also was attempted in 8 fresh human
      cadavers. RESULTS: In all dogs, the appendage was rapidly obliterated (21.3 +/-
      7.6 minutes) and confirmed at euthanasia at 11 weeks. In 3 cadavers, anatomic and
      disease factors prevented visualization of the left atrial appendage; in 1 the
      appendage tore, and in the remainder the appendage was obliterated. CONCLUSIONS:
      Obliteration of the left atrial appendage is feasible and may be considered as an
      additional surgical procedure to reduce stroke. The group of patients in whom it
      offers the greatest potential are those with atrial fibrillation deemed
      ineligible for warfarin, those without atrial thrombus and with a free
      pericardial and pleural space.

PMID- 8572769
TI  - Multivariate analysis of factors affecting waiting time to heart transplantation.
AB  - BACKGROUND: The growing clinical success of cardiac transplantation has resulted
      in a dramatic increase in the number of patients referred and subsequently listed
      for cardiac transplantation. Paradoxically, in the presence of a limited donor
      organ pool, such expansion has increased both the waiting time for
      transplantation and the number of patients dying while on the waiting list.
      METHODS: We performed univariate and multivariate analyses of the waiting times
      of 301 patients listed for transplantation using a Cox proportional hazards model
      to evaluate the simultaneous effect of multiple variables on the waiting time of
      heart transplant candidates. Variables considered included age, sex, race, blood
      type, weight at listing, United Network for Organ Sharing (UNOS) status at
      listing, UNOS status at transplantation, and proportion of time on the waiting
      list as UNOS status 1. RESULTS: The mean waiting time for patients ultimately
      having transplantation was 170.2 +/- 206.0 days; the median waiting time was
      103.5 days. Age, sex, weight, blood type, and percent of time as UNOS status 1
      all had a significant impact on waiting time in the univariate analysis. By
      multivariate analysis, proportion of time as UNOS status 1, lower weight at
      listing, and blood type AB were all highly associated as predictors of a shorter
      waiting time. Weight at listing represented a continuous variable whose risk
      ratio for a shorter waiting time correlated in such a way that the risk of a
      longer waiting time increased 2.3 per 22.5-kg (50-pound) increase in weight.
      Blood types A and B, although associated with a shorter waiting time, correlated
      less strongly than the other three variables. CONCLUSIONS: Our findings from this
      multivariate analysis demonstrate that UNOS status, blood type, and weight were
      the variables that most strongly affected overall waiting time for
      transplantation. It is our hope to define more accurately a group of patients
      with both a high likelihood of a long waiting time and a prohibitive risk of
      death while on the waiting list, who therefore may benefit from surgical
      alternatives to transplantation.

PMID- 8572770
TI  - Comparison of UW solution and St. Thomas' solution in the rat: importance of
      potassium concentration.
AB  - BACKGROUND: University of Wisconsin solution (UW) is in limited clinical use for
      heart transplantation, but there are doubts about its efficacy and concerns about
      the effect of its high K+ concentration on endothelium. St. Thomas' solution with
      or without aspartate is widely used and is of proven efficacy. METHODS: Using a
      modified (starch-free) variant of UW (MUW) we studied: (1) recovery of function
      with UW compared with aspartate-containing St. Thomas' solution; (2) effect of
      elevation of K+ in St. Thomas' solution to the level in UW; and (3) effect of
      reduction of K+ in UW and addition of Ca2+ or aspartate. Isolated rat hearts
      underwent 7 hours of arrest at 1 degrees C using MUW with or without 20 mmol/L
      aspartate or using aspartate-containing St. Thomas' solution. RESULTS: Functional
      recovery with MUW (51.8% +/- 2.5%) was superior to that with aspartate-containing
      St. Thomas' solution (37.1% +/- 4.3%; p < 0.01). Addition of aspartate to MUW had
      no effect. During 6 hours of arrest, lowering the K+ in MUW from 125 mmol/L to 20
      mmol/L reduced functional recovery from 59.9% +/- 4.2% to 42.3% +/- 4.3% (p <
      0.01). The addition of 1 mmol/L Ca2+ had no effect. Elevation of K+ in St.
      Thomas' solution produced more rapid arrest but no improvement in recovery.
      CONCLUSIONS: The protective effect of starch-free UW is greater (+13%) than that
      of aspartate-enriched St. Thomas' solution. Reduction of K+ in UW to lessen
      possible deleterious effects would decrease its protective effect by about 30% to
      a level comparable with that of St. Thomas' solution.

PMID- 8572771
TI  - Importance of preserving the mitral subvalvular apparatus in mitral valve
      replacement.
AB  - BACKGROUND: This clinical study sought to determine whether mitral valve
      replacement (MVR) with the preservation of both anterior and posterior chordae
      tendineae (MVR group II) would be more effective on the improvement of left
      ventricular regional wall motion than MVR with the preservation of posterior
      chordae tendineae alone (MVR group I). METHODS: Postoperative left ventricular
      wall motion was analyzed by a centerline method in three groups of MVR--group I
      (n = 13), group II (n = 15), and repair group (n = 15)--for mitral regurgitation.
      Shortening fraction of chordal length was determined in 100 chords, and these
      chords were divided into five regions. RESULTS: The comparison of postoperative
      versus preoperative shortening fraction among the three groups revealed that
      postoperative wall motion improved more strikingly at apical and diaphragmatic
      regions in the MVR group II and repair group in comparison to the MVR group I.
      The postoperative shortening fraction at the apical region in the MVR group II
      was significantly increased in comparison to preoperative shortening fraction
      (preoperative, 3.68% +/- 1.87%; postoperative, 5.38% +/- 2.33%; p < 0.05).
      However, postoperative shortening fraction in cardiac base was decreased in the
      MVR group II as well as other two groups. CONCLUSIONS: The MVR with the
      preservation of both anterior and posterior chordae tendineae contributed to the
      improvement of left ventricular regional wall motion in the apical and
      diaphragmatic regions.

PMID- 8572772
TI  - Effect of HeartMate left ventricular assist device on cardiac autonomic nervous
      activity.
AB  - BACKGROUND: Clinical performance of a left ventricular assist device is assessed
      via hemodynamic parameters and end-organ function. This study examined effect of
      a left ventricular assist device on human neurophysiology. METHODS: This study
      evaluated the time course change of cardiac autonomic activity of 3 patients
      during support with a left ventricular assist device before cardiac
      transplantation. Cardiac autonomic activity was determined by power spectral
      analysis of short-term heart rate variability. The heart rate variability before
      cardiac transplantation was compared with that on the day before left ventricular
      assist device implantation. RESULTS: The standard deviation of the mean of the R
      R intervals of the electrocardiogram, an index of vagal activity, increased to 27
      +/- 7 ms from 8 +/- 0.6 ms. The modulus of power spectral components increased.
      Low frequency (sympathetic activity) and high frequency power (vagal activity)
      increased by a mean of 9 and 22 times of each baseline value (low frequency
      power, 5.2 +/- 3.0 ms2; high frequency power, 2.1 +/- 0.7 ms2). The low over high
      frequency power ratio decreased substantially, indicating an improvement of
      cardiac sympatho-vagal balance. CONCLUSIONS: The study results suggest that left
      ventricular assist device support before cardiac transplantation may exert a
      favorable effect on cardiac autonomic control in patients with severe heart
      failure.

PMID- 8572773
TI  - Impact of mechanical heart valve prosthesis sound on patients' quality of life.
AB  - BACKGROUND: The "click" sound of mechanical heart valve prostheses has been
      recognized as a disturbing factor for some patients after mechanical heart valve
      implantation. The factors determining the extent of disturbance remain
      controversial. METHODS: Ninety-five unmatched patients with six different valve
      types were examined (Duromedics-Edwards, Bjork-Shiley, St. Jude Medical,
      Medtronic, CarboMedics, and Omnicarbon), including 12 patients with double-valve
      replacement. Three groups (Bjork-Shiley, Duromedics-Edwards, and St. Jude
      Medical) were comparable in size. All patients were examined and interviewed, a
      hearing test was performed, and valve sounds were analyzed. Sound transmission
      was evaluated. RESULTS: The loudest valve was the Duromedics-Edwards prosthesis
      (mean, 84.2 dB[A] impulse) and the St. Jude Medical was the quietest (mean, 73.5
      dB[A] impulse). This ranking was independent of patient variables and valve
      position. Discomfort level correlated with hearing loss and loudness of the
      valve. Patients desiring a quieter valve had better hearing, had louder valve
      sounds, felt disturbed by the sound, had partners who felt disturbed, and were
      receiving coumarin for anticoagulation. Sound was transmitted predominantly by
      air conduction. The frequency analysis to identify different valves was
      unsatisfactory, but louder frequencies did correspond with hearing-impaired
      patients' audiograms. CONCLUSIONS: Our results emphasize the need for valve
      design changes, preoperative education about the sound, and inclusion of routine
      hearing tests into the preoperative workup.

PMID- 8572774
TI  - Latissimus dorsi muscle blood flow during synchronized contraction: implications
      for cardiomyoplasty.
AB  - BACKGROUND: Damage in latissimus dorsi muscle flaps has been reported after
      clinical and experimental cardiomyoplasty, and an ischemic origin has been
      suggested. METHOD: In situ, preconditioned latissimus dorsi muscles in 5 sheep
      were stimulated in either 1:1 (muscle: heart) or 1:2 synchrony with the systolic
      phase of the cardiac cycle, using a burst duration of either 21% or 35% of the
      cycle. Thoracodorsal artery blood flow and thoracodorsal venous lactate
      concentrations were measured before and immediately after a 3-minute period of
      stimulation. RESULTS: The exercise-induced augmentation of thoracodorsal artery
      blood flow was significantly (p < 0.05) less with a 1:2 regimen than a 1:1
      regimen, for both a 21% (88%; 95% confidence interval [CI], 55.6% to 127.3%
      versus 138.9%; CI, 97.6% to 188.8%) and 35% burst duration (123.2%; CI, 84.7% to
      169.9% versus 167.0; CI, 120.8% to 222.6%). After cessation of stimulation,
      reactive hyperaemia was observed in 3 of 5 animals with 1:1 21% burst
      stimulation, and in 5 of 5 animals with a 35% burst duration, but was not seen
      after 1:2 regimens. A significant (p < 0.01) increase in thoracodorsal venous
      lactate levels was present after 1:1 35% burst stimulation (34.9%; CI, 9.9% to
      65.6%), but lactate levels tended to fall when a 1:2 ratio was used (15.9%; CI, 
      3.2% to 31.5%; p < 0.1). CONCLUSIONS: One-to-one stimulation regimens may be
      detrimental to latissimus dorsi blood flow, and an adaptive, rather than fixed,
      burst duration may be preferable. These findings have important implications for
      the cardiomyoplasty procedure.

PMID- 8572775
TI  - Use of verapamil and nitroglycerin solution in preparation of radial artery for
      coronary grafting.
AB  - BACKGROUND: The radial artery (RA) has been used as an alternative arterial graft
      for coronary artery bypass grafting. This artery has been reported to be spastic;
      therefore, use of spasmolytic drugs (vasodilators) during the preparation of the
      RA is recommended. The combination of calcium antagonists and nitroglycerin
      (verapamil plus nitroglycerin, VG solution) has been suggested to be effective in
      other bypass grafts. This study was designed to investigate (1) the effect of the
      VG solution during preparation of the RA for coronary artery bypass grafting and
      (2) whether the effect would last for a prolonged period after topical use.
      METHODS: Ring segments of the RA taken from coronary artery bypass grafting
      patients were studied in organ chambers at a physiologic pressure. The relaxation
      effect of VG (30 mumol/L verapamil and 30 mumol/L nitroglycerin, n = 5) or
      papaverine (30 mumol/L, n = 5) was recorded in K+ (25 mmol/L potassium chloride)
      precontracted RA segments. Other segments taken from the RA were treated (n = 5)
      or not treated (n = 20, as the control) with the VG solution for 45 minutes
      before used for coronary artery bypass grafting. Both the VG-treated and
      nontreated segments were immersed in oxygenated Krebs solution and stored in a
      refrigerator at 4 degrees C for 24 hours. The contraction force to 100 mmol/L K+
      was compared between the two groups. RESULTS: The VG solution induced more rapid
      relaxation than papaverine (p < 0.05 from the first to the ninth minute). After
      10 minutes, both solutions induced full relaxation. The contraction to K+ (100
      mmol/L) in rings treated with VG solution for 45 minutes during operation was
      almost abolished 24 hours later (0.86 +/- 0.1 g). In contrast, the control
      segments (n = 20) taken from nontreated RA contracted with K+ to high force (5.0
      +/- 0.6 g; p < 0.001). CONCLUSIONS: The present study suggests that the
      combination of verapamil and nitroglycerin may provide a rapid onset, a complete
      relaxation, and a long-lasting vasorelaxant effect when used to prepare the RA
      for grafting. This study adds a new method to prevent RA spasm during coronary
      artery bypass grafting.

PMID- 8572776
TI  - The last generation of pericardial valves in the aortic position: ten-year follow
      up in 589 patients.
AB  - BACKGROUND: The first generation of pericardial valves has been withdrawn from
      the market because of excessively high rates of premature failure. With its
      original design, the Carpentier-Edwards pericardial valve has promised improved
      results. METHODS: In our institution, 589 patients underwent an isolated aortic
      valve replacement with a Carpentier-Edwards pericardial bioprosthesis between
      July 1984 and December 1993. The patients' mean age was 67.5 +/- 11.2 years, and
      49% of the patients were in New York Heart Association clinical class III or IV.
      The operative mortality rate was 2.3% (14 of 595). All patients but 4 were
      followed up for an average of 4.1 years after their operation, and total follow
      up was 2,408 patient-years. RESULTS: At the time of the study, more than 85% of
      the patients were in New York Heart Association class I or II. There were 79 late
      deaths. After 10 years, the actuarial survival rate was 71% +/- 7%. Nineteen
      patients died of valve-related causes (3 endocarditis, 7 thromboembolic
      complications, 1 structural failure, and 8 sudden deaths). The actuarial rate of
      freedom from valve-related death was 94% +/- 3% at 10 years. Valve-related
      complications included 23 thromboembolic episodes (0.9% per patient-year), 14
      endocarditis (0.5% per patient-year), 9 reoperations (0.4% per patient-year), and
      4 structural valve failures with calcification and stenosis (0.2% per patient
      year). After 10 years, freedom from valve-related complications was 84% +/- 6%,
      from reoperation 97% +/- 2%, and from valve failure 96% +/- 4%. CONCLUSIONS:
      Because of its low rate of valve-related events at 10 years and low rate of
      structural deterioration with no leaflet tears, this prosthesis is an outstanding
      choice for patients who need tissue valves and for patients aged 60 years or
      older.

PMID- 8572777
TI  - Determinants of early and late results of combined valve operations and coronary
      artery bypass grafting.
AB  - BACKGROUND: Factors determining the outcome of operative correction of valvular
      abnormalities combined with coronary artery bypass grafting are still
      incompletely defined. METHODS: Determinants of early and late (more than 90 days)
      deaths and event-free survival were studied for combined valve operations and
      coronary artery bypass grafting in 741 patients using multivariate analysis.
      RESULTS: Ninety-day survival probability was 89% (95% confidence interval, 87% to
      92%). Preoperative risk factors for early death were age, female sex, renal
      failure, New York Heart Association class IV or V, and mitral insufficiency. The
      operative risk factor was the duration of aortic cross-clamping. Five- and 10
      year survival probabilities were 74% (95% confidence interval, 71% to 78%) and
      43% (95% confidence interval, 36% to 50%), respectively. Preoperative risk
      factors for late death were age, preoperative renal failure, New York Heart
      Association class IV or V, vessel disease, and nonsinus rhythm. Five- and 10-year
      event-free survival probabilities were 57% (95% confidence interval, 53% to 61%)
      and 23% (95% confidence interval, 17% to 28%), respectively. Preoperative risk
      factors for non-event-free survival were age, female sex, reduced left
      ventricular function, mitral regurgitation, and pacemaker rhythm. CONCLUSION: The
      demographic factors of age and female sex; the comorbid condition of renal
      failure; the cardiac conditions of advanced New York Heart Association class,
      left ventricular function, mitral regurgitation, vessel disease, and cardiac
      rhythm; and the operative condition of ischemia time are the most important
      predictors of clinical outcome after combined valve operations and coronary
      artery bypass grafting.

PMID- 8572778
TI  - Myocardial salvage by the use of reperfusion and intraaortic balloon pump:
      experimental study.
AB  - BACKGROUND: Thrombolytic therapy improves left ventricular ejection fraction and
      survival. The study was undertaken to evaluate the effects of intraaortic balloon
      pump used in conjunction with reperfusion in reducing infarct size. METHODS:
      Twenty-two dogs were subjected to proximal left anterior descending coronary
      artery occlusion. In group 1 (n = 7) occlusion lasted for 6 hours. In group 2 (n
      = 6) 2 hours of occlusion was followed by reperfusion. In group 3 (n = 9) after 2
      hours of occlusion the dogs were assisted with the intraaortic balloon pump
      throughout the 4 hours of reperfusion. At the end of 6 hours the infarcted
      myocardium of the left ventricle was determined and expressed as percentage of
      the myocardium at risk. RESULTS: In group 1, the infarcted myocardium was 79.3 +/
      9.9% of the myocardium at risk, in group 2, 59.0 +/- 19.9% (p < 0.05 versus
      group 1), and in group 3, 37.1 +/- 16.7% (p < 0.001 versus group 1 and p < 0.05
      versus group 2). Endocardial viability ratio was increased by the intraaortic
      balloon pump; in group 1 it was 1.02 +/- 0.14, in group 2, 1.25 +/- 0.24, and in
      group 3, 1.47 +/- 0.31 (p < 0.001 versus group 1 and p < 0.02 versus group 2).
      CONCLUSIONS: Reperfusion and intraaortic balloon pump increased salvage of the
      ischemic myocardium over that achieved by reperfusion alone in a canine occlusion
      reperfusion model.

PMID- 8572779
TI  - Efficacy of a partnership in enhancing Veterans Affairs cardiac transplantation
      activity.
AB  - BACKGROUND: Despite a nationwide surplus of cardiac transplantation programs, the
      number of United States armed forces veterans who receive heart transplants has
      declined over the past several years. This study reviews the efficacy of a
      partnership between a Veterans Affairs hospital and a university hospital in
      maximizing the access of veterans to the limited donor heart supply. METHODS: As
      part of a contract-based sharing agreement between the University of Wisconsin
      Hospital and the William S. Middleton Memorial Veterans Affairs Hospital, 25
      veterans underwent orthotopic heart transplantation between October 1993 and
      April 1995. Care of the patients was provided at the Veterans Affairs Hospital.
      The transplantation operations were performed at the University of Wisconsin
      Hospital, and all patients were transferred back to the Veterans Affairs Hospital
      5 to 7 days afterward. All patients were men (mean age, 52.1 +/- 2.1 years) and
      were referred from Veterans Affairs hospitals in nine different states. RESULTS:
      During the 19-month period, the average length of hospital stay for
      pretransplantation evaluation was 7.0 +/- 0.7 days (range, 2 to 15 days). Average
      status I waiting time was 26.9 +/- 3.3 days (range, 5 to 54 days); the average
      waiting time for status II was 115.1 +/- 16 days (range, 15 to 242 days).
      Posttransplantation length of stay at the Veterans Affairs Hospital was 22 +/-
      1.8 days (range, 11 to 41 days). Only 1 patient (4%) experienced a lethal
      postoperative complication. Ten patients (40%) exhibited graft rejection within
      the first month after transplantation, requiring treatment with augmented
      immunosuppressive therapy (steroids, orally in 2 patients and intravenously in
      8). The overall 30-day mortality rate was 4% (1 patient). The cause of death was
      acute grade 4 graft rejection 3 weeks after transplantation. Overall patient
      survival was 96%. CONCLUSIONS: A partnership between a Veterans Affairs hospital
      and a university hospital committed to transplantation can increase Veterans
      Affairs cardiac transplantation activity, with excellent 30-day mortality and
      early survival results.

PMID- 8572780
TI  - Influence of prolonged ventricular assistance on myocardial histopathology in
      intact heart.
AB  - BACKGROUND: The unloading effect of ventricular assistance on the injured
      myocardium may adversely affect the compensatory hypertrophy of the residual
      intact myocardium because myocardial protein synthesis is partly controlled by
      cardiac work. The influence of prolonged ventricular assistance on normal
      myocardium was evaluated from a pathologic point of view. METHODS: A ventricular
      assist device was chronically implanted in 5 goats using left atrium-aorta
      bypass. The pumping ratio was fixed at 70 beats/min. Left ventricular biopsy
      samples were taken before and 1 month after assistance. RESULTS: Although the
      volume densities of myocytes and interstitial tissue in the myocardium showed no
      significant changes after 1 month of support, the myocyte volume density to
      nuclear volume density ratio and the interstitial tissue volume density to
      nuclear volume density ratio decreased significantly (p < 0.01 and p < 0.05,
      respectively). A cross-sectional area of myocyte showed decreases of 20.9% to
      49.5%, whereas the nuclear cross-sectional area showed no significant changes. In
      addition, myofibrillar volume density in the cytoplasm decreased from 54.9 +/-
      2.3% to 49.1 +/- 4.4%. CONCLUSIONS: The results indicate that long-term
      ventricular assistance in the intact heart leads to myocardial atrophy. This
      suggests that in the damaged heart subjected to prolonged unloading by
      ventricular assistance, there is the possibility of limiting compensatory
      hypertrophic changes in the residual intact myocardium.

PMID- 8572781
TI  - Complete repair of PA-VSD with diminutive or discontinuous pulmonary arteries by
      transverse thoracosternotomy.
AB  - BACKGROUND: Optimal treatment and the optimal sequence of surgical and
      interventional steps to correct pulmonary atresia with ventricular septal defect
      and hypoplastic or discontinuous intrapericardial pulmonary arteries is still
      under discussion. Collateral arteries may be hardly accessible through median
      sternotomy at total correction. Bilateral transsternal thoracotomy gives wide
      access to the heart, both pleural spaces and hilar structures. METHODS: We used
      this incision for total correction of pulmonary atresia with ventricular septal
      defect in 6 patients. Three had Blalock-Taussig shunts placed previously, and
      intrapericardial pulmonary arteries were absent in all patients but 1, in whom
      they were hypoplastic. Central pulmonary arteries were enlarged with pericardial
      patches or replaced with tube grafts; the number of unifocalized collateral
      arteries varied between two and eight. RESULTS: One patient died of respiratory
      failure and sepsis (16.7%). Oxygen saturation increased from 76% (range, 65% to
      88%) preoperatively to 96% (range 91% to 99%) postoperatively. Mean postoperative
      pulmonary artery pressure was 30 mm Hg (range, 28 to 34 mm Hg). One patient had
      to be reoperated on through the same incision due to scarring and shrinkage of
      the peripheral anastomoses. Six months after operation 2 patients are in New York
      Heart Association functional class I and 2 are in class II. CONCLUSIONS:
      Transverse thoracosternotomy gives excellent access to the anatomical structures
      necessary to correct complex cases of pulmonary atresia with ventricular septal
      defect and may reduce the number of surgical procedures.

PMID- 8572782
TI  - Efficacy of ultrafiltration in removing inflammatory mediators during pediatric
      cardiac operations.
AB  - BACKGROUND: Conventional and modified ultrafiltration was used in pediatric
      cardiac operations to reduce volume overload and total body water. The purpose of
      this study was to compare the efficacy of these techniques in removing
      inflammatory mediators during cardiopulmonary bypass. METHODS: Fifty pediatric
      patients undergoing cardiac operations were randomized into a modified or
      conventional ultrafiltration group. Blood samples were obtained before and after
      ultrafiltration to assess the plasma concentrations of leukocyte elastase, tumor
      necrosis factor-alpha, interleukin-6, and interleukin-8. RESULTS: Except for
      plasma concentrations of tumor necrosis factor-alpha in the modified
      ultrafiltration group, the plasma concentrations of all the mediators measured
      increased after ultrafiltration in both groups of patients. The volume of
      ultrafiltrate and the total amounts of tumor necrosis factor-alpha and
      interleukin-6 removed by ultrafiltration were significantly greater in the
      modified group. The concentrations of mediators in the ultrafiltrate and the
      ratio of ultrafiltrate to plasma concentrations of the mediators did not differ
      between the groups. Ultrafiltration was more efficient in removing tumor necrosis
      factor-alpha than the other mediators. CONCLUSIONS: The efficacy in removing the
      inflammatory mediators generated during cardiopulmonary bypass did not differ
      between modified and conventional ultrafiltration.

PMID- 8572783
TI  - Should atrial septal defects in adults be closed?
AB  - BACKGROUND: By assessing current surgical outcome and symptomatic relief, this
      study attempts to answer whether atrial septal defects in adults should be
      closed. METHODS: Thirty-nine adult patients aged 35.2 +/- 13.6 years underwent
      operation for an atrial septal defect between June 1988 and June 1994.
      Indications for closure were symptoms (33 patients) or a significant left-to
      right atrial shunt (6 patients). Data were obtained from hospital records, and
      the latest status of the patients was determined by a written questionnaire.
      RESULTS: There were no deaths. Pulmonary embolism in 1 patient was the only
      complication observed. The QRS duration on the surface electrocardiogram
      decreased immediately (p < 0.001), and the cardiothoracic ratio on chest
      radiographs was significantly lower 3 to 6 months after operation (p < 0.001),
      both findings reflecting improved hemodynamics. No residual shunts were seen on
      follow-up (mean follow-up, 3.3 +/- 2.2 years). Twenty-seven (81.8%) of the 33
      symptomatic patients improved clinically in terms of exercise performance, atrial
      arrhythmias, or both. Three (50%) of the 6 previously asymptomatic patients
      reported improved functional capacity post-operatively. CONCLUSIONS: Today,
      operation for atrial septal defects in adults can be performed with no mortality
      and low morbidity and results in symptomatic improvement in the majority of
      patients. Clinical improvement was seen even in patients who considered
      themselves asymptomatic preoperatively. We advocate closure of atrial septal
      defects in adult patients with symptoms or significant atrial shunts.

PMID- 8572784
TI  - Anterior ischemic optic neuropathy after open heart operations.
AB  - BACKGROUND: The overall incidence of anterior ischemic optic neuropathy after
      open heart operations at the Lahey Clinic is less than 0.5%. However, during the
      2-year period, March 1, 1990, to March 1, 1992, an increased incidence (8 of 602
      patients or 1.3%) of this complication was observed. METHODS: A rigorous analysis
      was conducted of all 602 patients who underwent operation during this period.
      RESULTS: No preoperative risk factors were identified. The development of
      anterior ischemic optic neuropathy was associated with prolonged cardiopulmonary
      bypass time, low hematocrit levels, excessive perioperative body weight gain, and
      the use of epinephrine and amrinone. Other hypothetical risk factors include
      systemic hypothermia, anemia, increased intraocular pressure, and
      microembolization. Treatment options include the use of corticosteroid
      medications, reduction of intraocular pressure, and optic nerve fenestration,
      although recent evidence and our experience indicate that the fenestration
      procedure is of no benefit. CONCLUSIONS: Because all methods of treatment have
      had limited success, efforts to prevent this complication are of paramount
      importance.

PMID- 8572785
TI  - Retention of endothelium-dependent properties in human mammary arteries after
      cryopreservation.
AB  - BACKGROUND: We investigated the effects of cryopreservation and antibiotic
      treatment on endothelium-dependent vasomotor properties of human internal mammary
      arteries (IMAs). METHODS: Sixty IMA specimens from routine coronary artery bypass
      grafting procedures were randomly assigned to six groups. Group I (controls) were
      immediately tested after harvest. Remaining groups were prepared according to a
      stepwise design: group II, 6 hours of warm ischemia; group III, 6 hours of warm
      ischemia + 24 hours at 4 degrees C (without antibiotics); group IV, 6 hours of
      warm ischemia + 24 hours of 4 degrees C antibiotic disinfection; group V, 6 hours
      of warm ischemia + 24 hours at 4 degrees C (without antibiotics) +
      cryopreservation; and group VI, 6 hours of warm ischemia + 24 hours of 4 degrees
      C disinfection+cryopreservation. The IMA specimens were cut into rings and the
      tension of vascular smooth muscle was recorded. The IMA rings were contracted
      with norepinephrine (3 x 10(-6) mol/L) and tested with cumulative concentrations
      of acetylcholine (from 1 x 10(-9) to 1 x 10(-5) mol/L), contracted with
      endothelin-1 (from 1 x 10(-11) to 1 x 10(-6) mol/L), and contracted with the
      nitric oxide-synthase inhibitor NG-monomethyl-L-arginine (1 x 10(-4) mol/L).
      Rings were also tested for their capacity to generate 6-keto-prostaglandin F1
      (the stable metabolite of prostacyclin), and endothelial cell viability rate was
      finally evaluated with the trypan blue dye exclusion method. RESULTS: Our results
      show that a complete cryopreservation protocol does not significantly modify (p >
      0.05) the relaxant activity to acetylcholine in norepinephrine-precontracted IMA
      rings (controls; 90.2% +/- 4.2% vs group VI, 77.1% +/- 6.2%) or the
      vasoconstrictor response induced by endothelin-1 (controls, 62.6% +/- 2.8% versus
      group VI, 73.7% +/- 4.8%) and NG-monomethyl-L-arginine (controls, 22.4% +/- 1.5%
      versus group VI, 18.9% +/- 1.9%). Furthermore, IMA cryopreservation does not
      significantly modify (p > 0.05) the endothelial release of prostacyclin either in
      basal conditions (-20% versus controls) or during pharmacologic intervention with
      acetylcholine (-18% versus controls), endothelin-1 (-17% versus controls), and NG
      monomethyl-L-arginine (-18% versus controls). CONCLUSIONS: We conclude that the
      IMA endothelial function does not seem significantly injured by any of the
      current steps of disinfection and cryopreservation.

PMID- 8572786
TI  - Steroid administration in heart and heart-lung transplantation: is the timing
      adequate?
AB  - BACKGROUND: The release of cytokines after cardiopulmonary bypass may play an
      important role in postoperative morbidity. The release of proinflammatory
      cytokines, such as tumor necrosis factor alpha, interleukin (IL)-6 and IL-8, is
      even greater in patients undergoing heart transplantation (HTx) than coronary
      artery grafting. We tested the hypothesis that in HTx patients the earlier
      administration of steroids, before rather than after cardiopulmonary bypass as
      usual, can reduce the inflammatory response. METHODS: In 20 consecutive patients
      who underwent HTx or heart-lung transplantation (HLTx), plasma levels of tumor
      necrosis factor alpha, IL-6, IL-8, and anti-inflammatory cytokine IL-10 were
      measured before heparin administration, at aortic cross-clamping and declamping,
      and 0.5, 1, 1.5, 2, 4, 12, and 24 hours after aortic declamping. In 10 patients
      (group I, 6 HTx and 4 HLTx), 500 mg of methylprednisolone was first given as
      usual at 1.5 hours after aortic declamping (at the end of cardiopulmonary
      bypass). In the next 10 patients (group II, 6 HTx and 4 HLTx), the first doses of
      methylprednisolone were given 1 hour before operation. In both groups, 125 mg of
      methylprednisolone were given every 8 hours thereafter during the first
      postoperative day. RESULTS: The ischemic time and cardiopulmonary bypass time
      were similar in the two groups (166 +/- 16 minutes versus 157 +/- 13 minutes, and
      192 +/- 21 minutes versus 186 +/- 20 minutes, respectively, mean +/- standard
      error of the mean). At 30 minutes after aortic declamping and throughout the next
      4 hours, tumor necrosis factor alpha levels were significantly lower in group II
      than in group I (all p < 0.03). Interleukin-8 values 1 hour after declamping were
      also lower in group II than in group I (49 +/- 15 pg/mL versus 130 +/- 38 pg/mL,
      p < 0.02). Interleukin-10 levels were significantly higher in group II than in
      group I from 30 minutes after declamping through 2 hours after (all p < 0.03).
      Interleukin-6 levels were similar in the two groups. CONCLUSIONS: Earlier steroid
      administration in the immunosuppressive protocol for HTx or HLTx may be
      preferable to reduce the inflammatory response to cardiopulmonary bypass, as
      reflected by a lower production of tumor necrosis factor alpha and IL-8, and a
      greater release of IL-10.

PMID- 8572787
TI  - Comparisons of methods of myocardial hypothermia for cardiac transplantation.
AB  - BACKGROUND: Myocardial hypothermia of less than 10 degrees C is an essential
      component of preservation of donor hearts before implantation. Here we report
      temperature changes and comparison of methods for maintenance of myocardial
      hypothermia during implantation. METHODS: Twenty patients were prospectively
      randomized into two equal groups. In one cohort myocardial hypothermia was
      maintained by the "Stanford method" of continuous lavage of the pericardium and
      left atrium with refrigerated saline solution. In the other a cooling jacket was
      used without saline lavage. Temperatures at multiple sites were measured at 30
      second intervals from initiation of cardiac suturing until aortic cross-clamp
      removal. Comparisons were made between groups at each temperature site. RESULTS:
      The cooling jacket group temperatures were significantly lower at the left
      ventricular epicardium and endocardium than those of the Stanford method group.
      CONCLUSIONS: During cardiac implantation maintenance of myocardial hypothermia
      with a cooling jacket resulted in significantly deeper and more consistent
      hypothermia of the left ventricle than pericardial and left atrial lavage with
      refrigerated saline solution. Blood loss from aspirated saline lavage and
      perfusate dilution by the saline solution were eliminated.

PMID- 8572788
TI  - Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock.
AB  - BACKGROUND: Extracorporeal membrane oxygenation circuits have recently been
      introduced for extracorporeal life support (ECLS) in adult patients in
      cardiogenic shock and have been shown to provide excellent oxygenation and
      hemodynamic support. Heparin coating of the extracorporeal circuit provides a
      more biocompatible surface, which has been shown to minimize early surface
      induced complement activation and platelet dysfunction and hence may improve
      patient survival. This report reviews our experience with extracorporeal membrane
      oxygenation to treat postcardiotomy cardiogenic shock using minimal to no
      systemic heparinization in 23 patients. METHODS: During the 22-month period
      September 1992 through July 1994, 23 patients in cardiogenic shock were placed on
      venoarterial ECLS using a heparin-bonded circuit. These patients' charts were
      retrospectively reviewed. A logistic regression analysis of the variables
      collected was performed to identify clear-cut predictors of ability to be weaned
      from ECLS. RESULTS: Average patient age was 47.3 +/- 16.4 years (range, 5 to 72
      years). There were 17 male patients. Average time on ECLS was 58.4 +/- 35.1 hours
      (range, 0.5 to 144 hours). Statistical analysis revealed that patients unable to
      be weaned from ECLS were more likely to have a critically dilated left ventricle
      on echocardiography and were female. Ten patients (43.5%) died while on ECLS.
      Four patients were transferred to an implantable left ventricular assist device,
      and 3 underwent successful transplantation. The 9 other patients were
      successfully weaned from ECLS, and 4 were discharged home from the hospital.
      Overall, 7 patients (30.4%) who were placed on ECLS were successfully discharged
      home. CONCLUSIONS: Extracorporeal life support using an extracorporeal membrane
      oxygenation system provides excellent cardiac support with similar hospital
      survival rates as centrifugal mechanical support. Extracorporeal life support has
      complications unique to itself, but with time, these are likely to be overcome.
      Women and patients with persistent left ventricular dilatation are less likely to
      be weaned.

PMID- 8572789
TI  - Safety of repeat aprotinin administration for LVAD recipients undergoing cardiac
      transplantation.
AB  - BACKGROUND: Anecdotal reports of allergic and anaphylactic reactions after
      aprotinin therapy have raised concern that its repeat use may be associated with
      substantial morbidity. METHODS: To address this concern, we reviewed our
      experience with all patients who underwent implantation of a left ventricular
      assist device and subsequent cardiac transplantation with perioperative use of
      aprotinin. RESULTS: Twenty-three patients received full-dose aprotinin during
      left ventricular assist device implantation and subsequent cardiac
      transplantation. All patients tolerated primary exposure to aprotinin without
      complication. One episode of anaphylaxis after secondary exposure was treated
      with rapid institution of cardiopulmonary bypass. Although renal dysfunction was
      observed shortly after cardiac transplantation in 30.4% of patients, the effect
      was transient and occurred in the presence of cyclosporine. The one perioperative
      death after secondary exposure was unrelated to bleeding complications. No
      clinically evident thromboembolic events were documented. CONCLUSIONS: Primary
      and secondary exposure to aprotinin during operation with cardiopulmonary bypass
      is associated with limited intraoperative blood use, a low incidence of transient
      renal dysfunction and anaphylaxis, a rare need of reoperation for bleeding, and
      no clinical thromboembolic events.

PMID- 8572790
TI  - Impact of respiratory acid-base status in patients with pulmonary hypertension.
AB  - BACKGROUND: The perioperative management of patients undergoing mitral valve
      replacement (MVR) with pulmonary hypertension from mitral stenosis may be
      complicated by increased pulmonary vascular resistance. The purpose of this study
      was to examine the influence of respiratory acid-base status on the pulmonary
      hemodynamic indices of patients with pulmonary hypertension before and after MVR.
      METHODS: Ten patients with pulmonary hypertension from mitral stenosis (mean
      preoperative systolic pulmonary artery pressure, 73 +/- 8 mm Hg) undergoing MVR
      were studied in the operating room before and after MVR. Arterial partial
      pressure of carbon dioxide was manipulated by the addition of 5% carbon dioxide
      to the breathing circuit. Hemodynamic data were collected as the partial pressure
      of carbon dioxide rose from 30 mm Hg to 50 mm Hg and decreased back to 30 mm Hg.
      RESULTS: There were no differences in mean pulmonary artery pressure or pulmonary
      vascular resistance before and after MVR. Before MVR, mean pulmonary artery
      pressure increased from 32 +/- 1 mm Hg to 48 +/- 1 mm Hg as the partial pressure
      of carbon dioxide rose from 30 mm Hg to 50 mm Hg (p < 0.05), and pulmonary
      vascular resistance rose from 379 +/- 30 to 735 +/- 40 dynes.second.cm-5 (p <
      0.05). These effects on mean pulmonary artery pressure and pulmonary vascular
      resistance were not different after MVR. CONCLUSION: Respiratory acid-base status
      has a profound impact upon pulmonary vascular resistance in patients with
      pulmonary hypertension from mitral stenosis undergoing MVR. This impact persists
      in the immediate postoperative period. We conclude that respiratory acidemia
      should be avoided in these patients, whereas respiratory alkalemia may be used to
      help minimize pulmonary vascular resistance.

PMID- 8572791
TI  - Midterm angiographic study of five recycled mammary arteries during four coronary
      redos.
AB  - BACKGROUND: Recently the technical feasibility of reusing the left internal
      mammary artery (IMA) in coronary artery reoperation has been documented, but the
      patency of "recycled" IMAs has not yet been established. METHODS: In 4 patients
      undergoing coronary reoperation, five internal mammary arteries (3 left IMAs and
      2 right IMAs) that were patent but severely stenotic at the anastomotic site were
      taken down and reused. In 2 cases the IMAs were reanastomosed to the same target
      coronary artery, in 2 cases the IMAs were rerouted to another coronary artery,
      and in 1 case an interposition of a short segment of the greater saphenous vein
      was needed to reach the target coronary artery. RESULTS: Angiographic midterm
      evaluation, performed between 7 and 35 months postoperatively, showed patency of
      all the reused grafts without stenoses. CONCLUSIONS: When feasible, recycling of
      the IMAs may be considered if one or both IMAs have been previously used and are
      stenotic in the perianastomotic area, or when there is a stenosis in the native
      coronary artery distal to the anastomosis itself.

PMID- 8572792
TI  - Acute right ventricular failure during aortic valvular operation due to
      mechanical problem in the right coronary artery.
AB  - BACKGROUND: When right ventricular failure occurs during aortic valvular
      operation, inadequate myocardial protection may be the culprit. However, other
      causes of right ventricular failure should be considered, such as air or
      particulate matter embolization. Right ventricular failure unexpectedly occurred
      during an aortic valvular operation, and the cause was found to be a mechanical
      problem with the right coronary ostium. METHODS: A mechanical problem with the
      right coronary artery (RCA) occurred in 9 patients undergoing aortic valvular
      procedures, which included isolated aortic valve replacement (4 patients), aortic
      valve replacement and coronary artery bypass (1 patient), Bentall procedure (2
      patients), aortic valve reconstruction (1 patient), and double valve replacement
      and coronary artery bypass (1 patient). Although myocardial protection was
      considered to be the cause, a mechanical problem was subsequently identified in
      the RCA, leading that artery to be bypassed with a segment of saphenous vein.
      RESULTS: The 1 patient in whom the condition was not recognized at time of aortic
      valve operation died; at autopsy, a damaged and occluded right ostium was
      confirmed. The other 8 patients who had the RCA bypassed survived. CONCLUSIONS:
      We conclude that when right ventricular failure unexpectedly occurs during an
      aortic valvular operation and does not improve with reperfusion, a mechanical
      problem in the RCA should be considered. In this situation we recommend that the
      RCA be bypassed with a segment of saphenous vein graft.

PMID- 8572793
TI  - Successful management of massive pulmonary tumor embolism from renal cell
      carcinoma.
AB  - Renal cell carcinoma occasionally invades the inferior vena cava and rarely
      extends to the right atrium. However, despite the frequency of venous extension,
      it is unusual to recognize patients with massive pulmonary tumor embolus
      clinically. We describe a 60-year-old man who underwent pulmonary tumor
      embolectomy using cardiopulmonary bypass combined with profound hypothermia and
      intermittent low-flow perfusion. The patient is currently alive and well without
      implantation metastasis 6 months after the operation.

PMID- 8572794
TI  - Surviving resuscitation: successful repair of cardiac rupture.
AB  - An 83-year-old man was found unconscious and was successfully resuscitated.
      Progressive cardiac failure developed. After 42 hours of observation
      echocardiography revealed cardiac tamponade and a discontinuity in the left
      atrial wall. Exploration showed a laceration of the left atrium at the junction
      of the left pulmonary veins, which was closed with a direct suture on
      cardiopulmonary bypass. The postoperative course was uneventful.

PMID- 8572795
TI  - Posterior dislocation of the sternoclavicular joint leading to mediastinal
      compression.
AB  - Dislocations of the sternoclavicular joint are uncommon, and the posterior
      variety have a potential for considerable morbidity. We report a case with
      compression of the vital structures within the superior mediastinum. It was a
      rugby player getting run over by the scrum. The mechanism was an indirect force
      exerted forward and laterally against the shoulder. The patient complained of
      pain and dysphagia. A systolic right cervical murmur was heard. Angiography was
      normal and esophagography showed extrinsic esophageal compression. Surgical
      reduction was performed because there was a slight pneumomediastinum on the
      computed tomography. This case report demonstrates the mechanism, complications,
      and treatment of such a lesion.

PMID- 8572796
TI  - Major intrahepatic venovenous fistulas after a modified Fontan operation.
AB  - After the Fontan operation, systemic venous hypertension drives transpulmonary
      blood flow. Owing to this physiology, there is a significant incidence of
      effusions, splanchnic congestion, and generalized edema. To attentuate the
      effusive problems, partial exclusion of the hepatic veins has been recently
      practiced by Jacobs and Norwood. This report concerns a patient we recently
      treated for profound progressive cyanosis due to an acquired intrahepatic
      venovenous shunt after a Fontan operation with partial hepatic vein exclusion.

PMID- 8572797
TI  - Avoiding hypoxemia during unifocalization.
AB  - An 11-month-old child underwent unifocalization of the major aortopulmonary
      collateral arteries, but did not tolerate occlusion of both vessels
      simultaneously. Using a Y-shaped homograft tube, we translocated the vessels
      sequentially and avoided severe hypoxemia.

PMID- 8572798
TI  - Closure of a patent foramen ovale and tricuspid valve replacement after heart
      transplantation.
AB  - Patent foramen ovale has been noted after cardiac transplantation. Rarely is
      surgical intervention warranted. In this communication we report a case of severe
      tricuspid regurgitation and paradoxical embolism secondary to a patent foramen
      ovale in a patient 19 months after heart transplantation. The patient underwent
      successful closure of the patent foramen ovale and tricuspid valve replacement.

PMID- 8572799
TI  - Repair of tracheogastric fistula after cervical exenteration.
AB  - A case of tracheogastric fistula after laryngopharyngoesophagectomy for cervical
      esophageal cancer is described. The surgical management of the tracheogastric
      fistula is detailed and accompanied by a pertinent review of the literature. The
      one-stage repair in this report can provide an effective palliation or definitive
      treatment for this debilitating and unusual complication.

PMID- 8572800
TI  - Traumatic tricuspid valve injury: leaflet resuspension repair.
AB  - Blunt traumatic rupture of the tricuspid valve is exceedingly uncommon, and
      injury of the tricuspid valve due to penetrating trauma appears to be even more
      rare. Presented here is a case of tricuspid valve injury due to penetrating
      cardiac trauma repaired by leaflet resuspension 17 years later.

PMID- 8572801
TI  - Total vertebrectomy for en bloc resection of lung cancer invading the spine.
AB  - We describe a technique of total vertebrectomy for en bloc resection of a non
      small cell lung cancer with vertebral invasion through a combination of thoracic
      and enlarged posterior approaches, and present our entire experience of total and
      partial vertebrectomy for tumors invading vertebral bodies or the costovertebral
      angle.

PMID- 8572802
TI  - Hemangioma of the esophagus.
AB  - Hemangioma of the esophagus is a rare tumor. Fewer than 100 cases have been found
      in the literature. The present case report describes a patient who experienced a
      sudden massive hematemesis and demonstrated unusual changes on the computed
      tomographic scan.

PMID- 8572803
TI  - Peri-infarct pursestring for repair of subacute cardiac rupture.
AB  - A 55-year-old woman presented with cardiac tamponade after an inferior myocardial
      infarction. At surgical exploration there was an extensive area of hematoma
      associated with cardiac rupture. Rather than infarctectomy and ventricular repair
      an alternative approach was taken. The patient was successfully managed by the
      placement of a peri-infarct pursestring together with a superficial stitch
      closing the exit point of the cardiac rupture.

PMID- 8572804
TI  - Thigh ischemia complicating femoral vessel cannulation for cardiopulmonary
      bypass.
AB  - Compartment syndrome of the lower leg is an occasional complication of prolonged
      ischemia and reperfusion. Compartment syndrome of the thigh is a less well
      recognized complication. We present 2 patients with compartment syndrome of the
      ipsilateral thigh after femoral arterial and venous cannulation for
      cardiopulmonary bypass. Early diagnosis and urgent decompressive fasciotomy may
      limit the extent of local tissue damage and subsequent myonephropathic syndrome.

PMID- 8572805
TI  - Surgical therapy of pulmonary arterial aneurysms in Behcet's syndrome.
AB  - Two patients with Behcet's syndrome were operated for exsanguinating pulmonary
      artery aneurysm into a bronchus. Lower lobectomy was performed in the first
      patient. He died of hypoxia and sepsis on the 8th postoperative day.
      Pneumonectomy was undertaken in the second patient, who is well 30 months after
      the operation.

PMID- 8572806
TI  - Safe application of diagnostic laparoscopy during biventricular assistance.
AB  - We performed diagnostic laparoscopy in a patient who was critically unstable
      while on an ABIOMED BVS 5000 biventricular assist system. A relatively unique
      feature of the ABIOMED is the venous return being dependent only on gravity and
      the drawing force of venous return being the height of the inflow cannula
      compared with the level of the ABIOMED blood pump assembly; this did not preclude
      the use of pneumoperitoneum necessary for laparoscopy. The safe application of
      diagnostic laparoscopy in patients on a ventricular assist device is of
      importance in an era of increasing use of these devices and the increased
      potential for intraabdominal complications in this population.

PMID- 8572807
TI  - Right ventricular aneurysm associated with postinfarction ventricular septal
      defect.
AB  - Isolated right ventricular aneurysms are rare. Postinfarction right ventricular
      aneurysm associated with a ventricular septal defect is a very unusual
      complication. We present such a case that was successfully treated surgically.

PMID- 8572808
TI  - Coronary artery bypass grafting in a patient with antiphospholipid syndrome.
AB  - We report a 32-year-old female patient with antiphospholipid syndrome including
      severe coronary artery disease and multiple arterial and venous thrombosis. The
      patient had occlusion of the right internal thoracic artery, diffuse stenosis of
      the left internal thoracic artery, and occlusion of the left saphenous vein. The
      patient underwent successful coronary artery bypass grafting using the right
      gastroepiploic artery and a segment of the right saphenous vein. Antiphospholipid
      syndrome should be considered in young patients with myocardial infarction.

PMID- 8572809
TI  - Echocardiography-guided pericardiocentesis with a needle attached to a probe.
AB  - Pericardiocentesis with a needle attached to a probe was performed under two
      dimensional echocardiographic guidance in 9 patients with pericardial effusion
      after cardiac operations. The first 5 mm of the tip of a puncture needle for
      percutaneous transhepatic cholangiodrainage is scratched with a scalpel to give
      the tip high echo intensity. When the probe is placed on the skin, the direction
      of puncture at that probe angle appears automatically on the monitor.

PMID- 8572810
TI  - Intraoperative assessment of functioning mitral valve.
AB  - A technique is presented that allows intraoperative assessment of mitral valve
      function with the heart filling and actively beating. This technique secures
      steady coronary perfusion and avoids possible air embolism of the coronary
      arteries. Repeated assessment and repair during reparative mitral operations are
      greatly facilitated when this technique is accompanied by warm blood
      cardioplegia.

PMID- 8572811
TI  - Retrieval of crystalloid cardioplegic solutions.

PMID- 8572812
TI  - Simple wide-brimmed coronary perfusion cannula for the widely patent coronary
      ostium.
AB  - We describe a simply modified coronary perfusion cannula for the widely patent
      coronary ostium. This cannula is protective and adaptable to any size of the
      ostium, and ensures coronary perfusion without leakage.

PMID- 8572813
TI  - Rival trailblazers: the origins of successful closed valvular surgery.

PMID- 8572814
TI  - Appendage obliteration to reduce stroke in cardiac surgical patients with atrial
      fibrillation.
AB  - BACKGROUND: Left atrial appendage obliteration was historically ineffective for
      the prevention of postoperative stroke in patients with rheumatic atrial
      fibrillation who underwent operative mitral valvotomy. It is, however, a routine
      part of modern "curative" operations for nonrheumatic atrial fibrillation, such
      as the maze and corridor procedures. METHODS: To assess the potential of left
      atrial appendage obliteration to prevent stroke in nonrheumatic atrial
      fibrillation patients, we reviewed previous reports that identified the etiology
      of atrial fibrillation and evaluated the presence and location of left atrial
      thrombus by transesophageal echocardiography, autopsy, or operation. RESULTS:
      Twenty-three separate studies were reviewed, and 446 of 3,504 (13%) rheumatic
      atrial fibrillation patients, and 222 of 1,288 (17%) nonrheumatic atrial
      fibrillation patients had a documented left atrial thrombus. Anticoagulation
      status was variable and not controlled for. Thrombi were localized to, or were
      present in the left atrial appendage and extended into the left atrial cavity in
      254 of 446 (57%) of patients with rheumatic atrial fibrillation. In contrast, 201
      of 222 (91%) of nonrheumatic atrial fibrillation-related left atrial thrombi were
      isolated to, or originated in the left atrial appendage (p < 0.0001).
      CONCLUSIONS: These data suggest that left atrial appendage obliteration is a
      strategy of potential value for stroke prophylaxis in nonrheumatic atrial
      fibrillation.

PMID- 8572815
TI  - Optimal myocardial preservation: cooling, cardioplegia, and conditioning.
AB  - Myocardial preservation techniques have evolved in conjunction with cardiac
      surgery and currently offer substantial protection against myocardial injury. We
      propose that cardiac preconditioning, a robust, endogenous mechanism of
      cardioprotection, is emerging as an important adjunct to current cardioplegic
      techniques. By reviewing the physiologic basis for current cardioplegic
      strategies, and understanding the cardioprotective benefits of preconditioning,
      we postulate that cardiac preconditioning may represent an important, clinically
      accessible component of myocardial protection.

PMID- 8572816
TI  - As originally published in 1993: En bloc and standard esophagectomies by
      thoracoscopy. Updated in 1996.

PMID- 8572817
TI  - Coronary-coronary artery bypass.

PMID- 8572818
TI  - Aminoglycoside toxicity after sternal wound irrigations.

PMID- 8572819
TI  - Cellular cardiomyoplasty.

PMID- 8572820
TI  - Cannula length and arch flow erosion.

PMID- 8572821
TI  - Tranexamic acid use during coronary artery bypass grafting.

PMID- 8572822
TI  - Closed mitral valvotomy: tactile control.

PMID- 8572823
TI  - Radial artery in coronary artery bypass grafting.

PMID- 8572824
TI  - Endobronchial stents.

PMID- 8572825
TI  - Implications of cost in treatment selection for patients with coronary heart
      disease.
AB  - BACKGROUND: The growth of managed care and other types of capitated payment
      systems for medical care has forced cost into the therapeutic equation. The
      benefits of treatment must now be balanced against their costs. Clinicians are
      being challenged to prove that what they do has sufficient "value." Particular
      targets for these challenges are surgeons and interventional cardiologists who,
      in aggregate, perform expensive high-volume procedures. METHODS: A cost analysis
      of percutaneous transluminal coronary angioplasty, coronary artery bypass
      grafting, and medical management of coronary artery disease has been undertaken
      using the Duke University database of 4,000 patients. The costs of the three
      procedures were compared at several fixed time points. RESULTS: The costs for the
      three treatments are critically dependent on the time points selected for
      comparison. At 60 days, the cost of the medical group was about one quarter the
      cost of the bypass group, whereas the cost of the angioplasty group was on
      average 60% of that of the surgical group. By 1 year, the costs in the
      angioplasty group reached 66% of those in the bypass group, but both remained far
      above the costs of medical therapy alone. There is a significant cost gradient
      for percutaneous transluminal coronary angioplasty as the extent of the disease
      increases, which is not apparent for coronary artery bypass grafting.
      CONCLUSIONS: Medical costs arise in a complex manner, and their prediction is
      difficult. Unexpected events during or after the initial treatment are a major
      cause of increased costs, and complications often cannot be predicted. Patient
      related factors have only a small effect on costs in comparison with the choice
      of treatment. High-risk, high-cost patients tend to get the most benefit.

PMID- 8572826
TI  - Cardiac surgery in a fixed-reimbursement environment.
AB  - Hospital and physician services in Canada are funded by public (government)
      sources. This article will describe the practice of cardiac surgery in this
      setting. Federal legislation has prescribed the principles of accessibility,
      universality, comprehensiveness, portability, and public administration for
      essential healthcare services in Canada. Provincial and territorial governments
      are responsible for the provision of services, receiving federal tax and cash
      transfers that supplement provincial/territorial funds for hospital, physician,
      and community health services. Hospitals negotiate annually for global budgets.
      Physicians work as independent contractors in hospitals (and communities) and are
      usually paid as specified by fee-for-service contracts negotiated at intervals
      with governments. Cardiac surgical services have been planned conjointly with
      government. Forty-two centers in Canada serve a population of 28 million. All but
      three of these centers are located in tertiary teaching hospitals; all but one do
      more than 200 pumps annually. The rate of cardiac operations is 80 per 100,000
      population. In Ontario, the Provincial Adult Cardiac Care Network makes
      recommendations to governments about the distribution of the 7,600 pumps annually
      (population, 11 million), rationalizing waiting lists based on an urgency rating
      scale. Patients requiring emergent/urgent operations are well served. The average
      waiting time for an elective cardiac operation is 10.5 weeks. The waiting list
      mortality is less than 0.5%. The Provincial Adult Cardiac Care Network also
      determines the placement of new programs and participates in creating hospital
      funding formulas developed from a combination of resource and acuity intensity
      weighting. Most surgeons hold full-time academic appointments but are funded
      largely by practice income. Surgical fees average $2,000 (Canada) per case.
      Overhead, including malpractice insurance, is approximately 45%. All Canadian
      patients enjoy reasonably timely access to good cardiac surgical care. Further
      constraints on physician compensation and (academic) hospital funding will
      compromise this balance.

PMID- 8572827
TI  - Outcome analysis using hazard function methodology.
AB  - BACKGROUND: The hazard function is the instantaneous rate of occurrence of a time
      related event, such as death. Methods exist to determine the hazard function from
      clinical outcome (follow-up) data, to identify risk factors for higher hazard,
      and to generate patient-specific predictions. In this article, hazard function
      methodology is extended to the arena of healthcare costs. METHODS: Using a
      compartmental analogue, a hazard function method is introduced to analyze patient
      specific distributions of hospital costs, charges, or length of stay when these
      are truncated by the competing risk of in-hospital death. Another hazard function
      method is proposed to analyze time-related healthcare costs, exploiting weighted
      repeated events theory. RESULTS: Successful application of the hospital costs
      methodology in the hazard function domain is demonstrated for length-of-stay data
      after coronary artery bypass grafting. A previously reported analysis of variable
      morbidity from repeated thromboembolic events illustrates the weighted events
      methods. CONCLUSIONS: Existing hazard function methodology can be extended to
      analyze healthcare costs, either of a single episode of care or of multiple time
      related episodes.

PMID- 8572829
TI  - Mechanisms to reduce hospital stays.
AB  - BACKGROUND: The present era of medicine is concerned to a large measure with cost
      containment and the advent of managed care. For these reasons the concept of
      reducing hospital stays with a concomitant reduction in hospital cost is very
      attractive. The role of fast track is to ensure that we are not placing the
      patient at any additional risk and in fact are improving recovery and patient
      well-being. METHODS: Fast track is based on a specific protocol that is followed
      for each patient. Intensive preoperative education of patient and family
      familarize them with early discharge. Anesthetic technique is modified to effect
      early (4 to 8 hours) postoperative extubation. Steroids are administered
      perioperatively to improve myocardial function and reduce the release of
      inflammatory mediators. Digoxin is given prophylactically as are the bowel
      mediating drugs metoclopramide, docusate, and ranitidine. The fast-track protocol
      is associated with aggressive ambulation of the patients and cardiac
      rehabilitation, so that the patient is out of bed the first day after operation,
      walking in the hall the second day, and up a flight of stairs the third day.
      RESULTS: A shift to fast track in 1992 permitted comparison between 282 non-fast
      track patients and 280 fast-track patients undergoing coronary artery bypass
      grafting. The results showed no adverse consequences of fast track. Forty-eight
      percent of fast-track patients were discharged at 3 to 5 days compared with 26%
      of non-fast-track patients. No significant differences were found between the two
      groups with respect to infection (1%), operative mortality (approximately 4%),
      and 30-day hospital readmission (7% non-fast-track and 8% fast-track). A
      postdischarge questionnaire addressed issues of patient and family satisfaction.
      The early discharge patient had a 77% comfort level, whereas their family members
      felt satisfied with a 3- to 5-day hospital stay in only 54% of cases. These data
      suggest the need for better communication, education, and additional
      postdischarge support systems. CONCLUSIONS: A fast-track protocol allows faster
      recovery and earlier discharge from both the intensive care unit and the hospital
      without apparent increased risk. Complicated patients can also be fast tracked,
      and the desire to do so may actually expedite recovery.

PMID- 8572828
TI  - Cost/benefit analysis of pharmacologic hemostasis.
AB  - BACKGROUND: Surgical bleeding with possible associated coagulopathies is a major
      source of morbidity and mortality. More than 27% of patients receive unnecessary
      blood or blood-product transfusions during cardiac operations. Analysis of the
      cost-benefit of pharmacologic hemostasis can be accomplished by relating all the
      components of cost, which include both direct and indirect costs to both direct
      and indirect benefits to the patient. METHODS: A significant reduction in
      transfusion requirements can be achieved by the systematic application of a
      clinical algorithm. An alternative is to use drugs that enhance hemostasis. Four
      such drugs commonly used are desmopressin acetate, tranexamic acid, epsilon
      aminocaproic acid, and aprotinin. All these agents have been shown to
      successfully reduce bleeding and the need for transfusion. It appears that the
      order of efficacy (greatest to least) is aprotinin, tranexamic acid, epsilon
      aminocaproic acid, and desmopressin acetate. RESULTS: Cost/benefit analysis
      associated with the use of these agents is complex. The direct costs of these
      drug treatments can be balanced against the costs related to blood and blood
      product administration. Using epsilon-aminocaproic acid, blood used is valued at
      $30, whereas the drug treatment cost is less than $2. Aprotinin use results in
      costs of more than $500, with the drug costing $900. CONCLUSIONS: Improved
      hemostasis should also result in indirect cost savings from reduced operating
      room time, reduced intensive care unit and hospital stay, and the avoidance of
      reoperation for bleeding.

PMID- 8572830
TI  - Analysis of costs associated with CABG and PTCA.
AB  - BACKGROUND: Factors related both to the patient and to the healthcare provider
      affect the costs of percutaneous transluminal coronary angioplasty (PTCA) and
      coronary artery bypass grafting (CABG). The costs of both PTCA and CABG are most
      highly dependent on the occurrence of complications in the postprocedure period.
      Costs are lower in centers that have adequate procedure volumes, due partly to
      economics of scale and partly to improved outcomes. METHODS: The relative costs
      of PTCA and CABG in patients suitable for either procedure is being investigated
      in several ongoing randomized clinical trials. The cost-effectiveness of coronary
      revascularization relative to medical therapy has also been investigated. The
      cost-effectiveness of PTCA relative to medical therapy has not been evaluated.
      RESULTS: The initial cost of PTCA is roughly half that of CABG, but costs are
      similar after 2- or 3-year follow-up because of the need for repeat
      revascularization procedures in patients initially treated with PTCA. The data on
      cost-effectiveness of coronary revascularization relative to medical therapy have
      shown that CABG is particularly cost-effective in patients for whom survival is
      improved or in whom symptoms of severe angina are relieved. CONCLUSIONS:
      Percutaneous transluminal coronary angioplasty and CABG are costly but effective
      therapies. Clearly PTCA costs less initially but the follow-up costs are much
      higher. The cost-effectiveness of coronary revascularization can be improved by
      maintaining adequate procedural volumes, reducing procedural complications, and
      selecting patients properly.

PMID- 8572832
TI  - ACE inhibitors as a shield against diabetic nephropathy.

PMID- 8572831
TI  - Clinical usefulness of risk-stratified outcome analysis in cardiac surgery in New
      Jersey.
AB  - BACKGROUND: The results of aortocoronary bypass grafting are under increasing
      scrutiny by the Health Care Financing Agency, health maintenance organizations,
      and the news media. Surgeons and hospital administrators are concerned that
      erroneous conclusions may be drawn from raw outcome data, which do not reflect
      the patient's preoperative condition. It is our contention that any realistic
      comparison of results among surgeons or institutions must take that condition
      into account through a process of risk management. METHODS: We have developed a
      statistical model for risk stratification based on data compiled systematically
      at the Newark Beth Israel Medical Center since 1980. Univariate analysis and
      stepwise logistic regression are used to identify the most significant risk
      factors and determine the appropriate weight for each. Our original risk
      stratification system has now been updated by eliminating the optional fields and
      reweighting the variables. This has reduced the subjective input and improved the
      accuracy. RESULTS: Use of the modified system shows good correlation between
      expected and observed outcomes at our institution and in other cases reported to
      the New Jersey Department of Health. It has improved the results especially in
      high-risk cases: in total, a group of 5,336 patients have been assessed by the
      modified system: the expected mortality overall was 7.2% and the observed
      mortality was 5.4%. In 1,280 high-risk patients, ie, those with an expected
      mortality of greater than 11%, the expected mortality was 16.2% and the observed
      mortality was 12.3%. CONCLUSIONS: Our results suggest a decline in length of
      hospital stay and beneficial changes in operative procedures. They also indicate
      that exclusion of high-risk cases will result in only minimal financial savings,
      perhaps less than 2%.

PMID- 8572833
TI  - Restless legs syndrome. A review.
AB  - Restless legs syndrome is characterized by unpleasant, deep-seated paresthesias
      in the legs and sometimes the arms. These sensations occur at rest and are
      relieved by movement. Sleep disturbance is common. Many patients also have
      periodic movements of sleep. Mild symptoms of restless legs occur in up to 5% of
      the population. Restless legs syndrome is idiopathic in most patients, but it may
      be the presenting feature of iron deficiency and is also common in uremia,
      pregnancy, diabetes mellitus, rheumatoid arthritis, and polyneuropathy. Treatment
      of the underlying cause, when possible, usually relieves the symptoms. For
      patients with severe symptoms, levodopa, bromocriptine mesylate, opioids,
      carbamazepine, clonazepam, and clonidine hydrochloride have proved to be
      effective.

PMID- 8572834
TI  - Ethical and legal issues in nursing home care.
AB  - Physicians who provide care for nursing home residents are regularly challenged
      by ethical and legal issues. Because nursing home care is complicated by numerous
      regulations and because nursing home residents have complex medical and social
      problems, some issues are unique to the long-term care setting and others present
      in unfamiliar ways. Some issues frequently encountered in this context are
      discussed: advance directives, competence and decision-making capacity, decisions
      about life-sustaining treatment, resident abuse, restraints, psychotropic
      medications, risk management, participation in research, and ethics committees.
      With knowledge of the legal and ethical framework and understanding of some of
      the common, complicated issues that arise, physicians should be better equipped
      to provide optimal care for nursing home residents.

PMID- 8572835
TI  - Efficacy of insulin and sulfonylurea combination therapy in type II diabetes. A
      meta-analysis of the randomized placebo-controlled trials.
AB  - BACKGROUND: Numerous studies demonstrate the efficacy of the combination therapy
      of insulin and sulfonylurea in subjects with type II diabetes mellitus. However,
      two recent meta-analyses of randomized trials during the last decade provided
      inconsistent conclusions and failed to resolve the controversy. OBJECTIVE: To
      assess the efficacy of insulin and sulfonylurea combination therapy in type II
      diabetes mellitus by performing meta-analysis of only the controlled studies
      selected according to specific strict criteria. METHODS: A computerized
      literature survey was conducted using the MEDLINE database from January 1980
      through March 1992 with the search headings of "sulfonylurea" and "insulin" and
      "combination therapy in diabetes mellitus. "A manual search was also performed
      using references from each retrieved report. Case reports, review articles,
      editorials, and citations reported in non-English-language journals without
      English translations were excluded. Forty-three citations were obtained. Four
      strict inclusion criteria were used to select studies: randomized, placebo
      controlled trials (oral agent plus insulin vs placebo plus insulin); homogeneous
      target population (subjects with type II diabetes); intervention using the same
      sulfonylurea agent in a combination therapy; and uniform outcome measures to
      evaluate efficacy such as body weight; values for serum glucose, glycohemoglobin,
      and C peptide; daily insulin dosage; and lipid concentrations. More stringent
      qualitative subcriteria were then used to eliminate bias in the final unanimous
      selection by two blinded reviewers. Data were pooled and analyzed using Student's
      t test and Winer's combined test. RESULTS: Sixteen studies satisfied the
      inclusion criteria. Metabolic control improved with the combination therapy as
      reflected by a significant lowering of fasting serum glucose values (P < .01) and
      glycohemoglobin concentrations (P < .025). Moreover, improved metabolic control
      was achieved with a significantly smaller daily insulin dose (P < .01) and
      without a significant change in body weight. Finally, the combination therapy
      enhanced the endogenous insulin secretion as expressed by an increase in fasting
      serum C peptide concentration (P < .05). CONCLUSIONS: Combination therapy with
      insulin and sulfonylurea may be a more appropriate and a suitable option to
      insulin monotherapy in subjects with non-insulin-dependent diabetes in whom
      primary or secondary failure to sulfonylurea developed. It may also be a more
      cost-effective way of long-term management in this group of subjects, especially
      in the elderly.

PMID- 8572836
TI  - Improvement in quality of life and exercise capacity after coronary bypass
      surgery.
AB  - BACKGROUND: Outcome after coronary artery bypass grafting is usually evaluated by
      exercise stress testing. Increased exercise capacity and reduced angina pectoris
      have been equated with improved quality of life, but this represents a limited
      view. OBJECTIVE: To prospectively evaluate the effects of coronary artery bypass
      grafting on quality of life and exercise capacity and their interrelationship.
      METHODS: In a consecutive series of patients (N = 2365) who underwent coronary
      artery bypass grafting, we administered a questionnaire to assess quality of life
      before and 2 years after surgery. A standardized exercise test was performed
      during the year before surgery and 2 years after. A preoperative exercise test
      was performed by 726 patients. Among these patients, 462 completed a quality-of
      life questionnaire preoperatively and 578 did so postoperatively. Preoperative
      and postoperative exercise tests were obtained from 362 patients. RESULTS: The
      improvement in quality of life was related to the severity of preoperative angina
      (P < .001) and female sex (P = .004) and was inversely related to preoperative
      exercise performance (P = .04). The improvement in exercise capacity was greater
      among men (P < .001) and was inversely related to preoperative exercise capacity
      (P < .001). CONCLUSIONS: The greatest improvement in quality of life after
      coronary artery bypass grafting appeared in those patients with the most impaired
      exercise capacity, those with the most severe angina pectoris, and women.
      Improvement in exercise capacity was greatest in patients with the poorest
      preoperative exercise capacity and in men. These findings indicate that exercise
      testing is of limited value as a measure of quality of life and that assessment
      by a questionnaire has a complementary place.

PMID- 8572837
TI  - Losartan and low-dose hydrochlorothiazide in patients with essential
      hypertension. A double-blind, placebo-controlled trial of concomitant
      administration compared with individual components.
AB  - BACKGROUND: Angiotensin II acts at the cellular level through specific
      angiotensin II subtype I, AT-1 receptors. Losartan is the first of a new class of
      antihypertensive agents that specifically block angiotensin II at AT-1 receptors.
      By acting on complementary and different pharmacologic mechanisms, the
      concomitant use of low doses of hydrochlorothiazide with losartan may offer an
      additive antihypertensive activity with fewer adverse experiences. METHODS: This
      double-blind study evaluated losartan concomitantly administered with
      hydrochlorothiazide as initial therapy in 703 patients with essential
      hypertension. RESULTS: The greatest reduction in blood pressure was observed in
      the 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide group (17.2 mm
      Hg in sitting systolic blood pressure and 13.2 mm Hg in sitting diastolic blood
      pressure [P < or = .001]), and the effects of the two components appeared to be
      additive. Seventy-eight percent of the patients treated with 50 mg of losartan
      potassium and 12.5 mg of hydrochlorothiazide had an excellent or good
      antihypertensive response (sitting diastolic blood pressure < 90 mm Hg or > or =
      90 mm Hg with a reduction of 10 mm Hg or more). Peak (6 hours after dosing) and
      trough placebo-adjusted ratios for the losartan-hydrochlorothiazide groups ranged
      from 62% to 85%, indicating that there was a smooth reduction in sitting
      diastolic blood pressure that was sustained over 24 hours. The most common
      clinical adverse experiences (> or = 4%) that occurred with an incidence slightly
      greater than that reported by the placebo-treated patients were headache,
      asthenia or fatigue, dizziness, sinusitis, and upper respiratory infection.
      CONCLUSION: The concomitant administration of losartan potassium, 50 mg, with
      12.5 mg of hydrochlorothiazide once daily produced an additive reduction in
      trough sitting systolic and diastolic blood pressure and was well tolerated.

PMID- 8572838
TI  - Long-term renoprotective effect of angiotensin-converting enzyme inhibition in
      non-insulin-dependent diabetes mellitus. A 7-year follow-up study.
AB  - BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease
      in developed countries. Duration of diabetes, blood pressure values, and
      metabolic status are the major determinants of the course of nephropathy, and
      microalbuminuria is the hallmark of its onset. Angiotensin-converting enzyme
      inhibitors offer important renoprotection to hypertensive and normotensive
      patients with insulin-dependent diabetes mellitus and non-insulin-dependent
      diabetes mellitus. Our study extends previous observations for duration and the
      effect of angiotensin-converting enzyme inhibition on advanced nephropathy.
      METHODS: Double-blinded (first phase) and open (second phase) randomized
      controlled study of 7 years. Ninety-four normotensive patients with non-insulin
      dependent diabetes mellitus whose serum creatinine levels were lower than 123.76
      mumol/L (1.4 mg/dL) and who had microalbuminuria (30 to 300 mg/24 h) were given
      enalapril maleate, 10 mg/d, or placebo, for 5 years. For 2 more years they were
      followed up openly and given the choice to receive enalapril or no treatment.
      RESULTS: In the enalapril-treated patients, albuminuria remained stable for 7
      years. An increase from (mean +/- SD) 123 +/- 58 to 310 +/- 167 mg/24 h occurred
      in the untreated group after 5 years, and a further increase to (mean +/- SD) 393
      +/- 223 mg/24 h occurred after 7 years. Reciprocal creatinine was unchanged in
      treated patients for 7 years; in the untreated patients, the mean decline was 13%
      at 5 years and 16% at 7 years. Treatment with enalapril resulted in an absolute
      risk reduction of 42% for nephropathy to develop during 7 years (95% confidence
      interval, 15% to 69%; P < .001, Student's t test). Glycosylated hemoglobin and
      body mass index remained unchanged. CONCLUSIONS: Angiotensin-converting enzyme
      inhibition offers long-term protection against the development of nephropathy in
      normotensive patients with noninsulin-dependent diabetes mellitus who have
      microalbuminuria, and it stabilizes renal function in previously untreated
      patients with impaired renal function. Discontinuation of treatment results in
      renewed progression of nephropathy.

PMID- 8572839
TI  - Physician practices regarding anticoagulation and cardioversion of atrial
      fibrillation.
AB  - BACKGROUND: Stroke is one of the most significant potential complications in
      patients who are undergoing cardioversion for atrial fibrillation. To minimize
      the risk of stroke, the American College of Chest Physicians' (ACCP's) Third
      Consensus Conference on Antithrombotic Therapy developed specific recommendations
      regarding anticoagulation before and following elective cardioversion of patients
      with atrial fibrillation. OBJECTIVE: To determine if patients undergoing
      cardioversion for atrial fibrillation are administered anticoagulants according
      to the ACCP's Third Consensus Conference on Antithrombotic Therapy
      recommendations. DESIGN: A retrospective review of cases of atrial fibrillation
      at a tertiary care teaching hospital to determine if physicians are routinely
      following these recommendations. METHODS: Data were collected for the year 1994
      for all patients admitted to a tertiary care teaching hospital with a diagnosis
      of atrial fibrillation (n = 111). The ACCP's recommendations that were evaluated
      included the following: patients undergoing elective cardioversion for atrial
      fibrillation should receive anticoagulation for 3 weeks before and 4 weeks
      following cardioversion except in cases of new-onset atrial fibrillation, and
      warfarin and heparin should be administered jointly for several days before
      discontinuation of heparin therapy. RESULTS: Of the 111 patients who presented
      with a diagnosis of atrial fibrillation, 51 underwent elective cardioversion. In
      18 (35%) of 51 cases, physicians failed to follow at least one of ACCP's
      recommendations regarding anticoagulation. These included failing to (1)
      administer anticoagulants to patients for 3 weeks before elective cardioversion
      (n = 14); (2) administer anticoagulants to patients for 4 weeks following
      cardioversion (n = 6); and (3) overlap heparin and/or warfarin therapies for 72
      hours (n = 4). Six cases failed to meet more than one of these recommendations.
      CONCLUSION: Physicians are not routinely following the ACCP's Third Consensus
      Conference on Antithrombotic Therapy recommendations regarding anticoagulation in
      elective cardioversion of atrial fibrillation, thus increasing patients' risk of
      stroke.

PMID- 8572840
TI  - Do actions reported by physicians in training conflict with consensus guidelines
      on ethics?
AB  - OBJECTIVE: To assess the extent to which actions reported by internal medicine
      trainees conflict with published guidelines on ethics. METHODS: A confidential
      survey was sent to a random sample (N = 1000) of associate members of the
      American College of Physicians (ACP). Questions were asked about ethical decision
      making in areas addressed by the guidelines in the ACP Ethics Manual. Quoted
      manual guidelines were provided, followed by 55 yes or no questions, such that a
      yes answer represented an action that conflicted with a guideline. There were two
      follow-up mailings to nonresponders. RESULTS: Forty percent (n = 397) completed
      the questionnaire; 17% indicated they were aware of the guidelines on ethics. On
      average, associates responded yes to 16% of questions where a yes response
      indicated they have acted outside guidelines on ethics one or more times. The
      mean number of responses (n = 55) that conflicted with a guideline was 7.6 per
      person (SD, 4.7 responses; range, 0 to 33 responses). Ninety-eight percent of
      respondents reported actions falling outside a guideline one or more times and
      80% did so four or more times. The most frequently reported reason (965/3219
      [30%]) from a list of four choices for acting outside a guideline was "I was
      aware of the guideline, but this did not represent an ethical dilemma to me."
      CONCLUSIONS: Few responding ACP associates indicated awareness of the ACP
      guidelines on ethics. Physicians in training nevertheless reported acting
      according to the presented guidelines most of the time, although nearly all
      respondents acted outside a guideline at least once, and some did so many times.
      Reported behaviors were sometimes inconsistent with consensus ethical standards
      that apply to internists. Physicians in training need to know more about ethical
      standards that apply to their own practice and should be aware when their actions
      deviate from ethical norms. Before acting outside guidelines on ethics, trainees
      should discuss their conflicts with others, such as attending physicians,
      clinical ethicists, or hospital ethics committees.

PMID- 8572841
TI  - Efficacy of the National Cholesterol Education Program Step I diet. A randomized
      trial incorporating quick-service foods.
AB  - OBJECTIVE: To determine the effect of incorporating quick-service meals into a
      Step I diet on the achievement of the National Cholesterol Education Program
      (NCEP) guidelines and on the blood lipid response of hyperlipidemic subjects (as
      possibly, the achievement of, and adherence to, dietary goals may be assisted by
      the inclusion of familiar foods, instead of their exclusion). METHODS: This was a
      randomized, parallel design study in free-living subjects. Hypercholesterolemic
      men and women (low-density lipoprotein cholesterol [LDL-C] level, 3.36 to 5.69
      mmol/L [130 to 220 mg/dL]) who were consuming a high-fat diet (> 33% of total
      calories from fat) were randomly assigned to either a traditional NCEP Step I
      diet (n = 44) or an NCEP Step I diet with the incorporation of frequent quick
      service meals (NCEP-QS, n = 45). RESULTS: After 8 weeks of treatment, both groups
      similarly reduced their reported dietary intakes of energy (approximately 30%),
      total percent fat (approximately 8%), percent saturated fat (approximately 3%),
      and cholesterol (approximately 38% to 28%). Both groups also experienced a
      decrease in the levels of total serum cholesterol (NCEP Step I diet, 8%; NCEP-QS
      Step I diet, 3%) and LDL-C (NCEP Step I diet, 10%; NCEP-QS Step I diet, 4%).
      However, compared with the group receiving the NCEP-QS Step I diet, the subjects
      who were consuming the NCEP Step I diet showed a significantly greater reduction
      in their total serum cholesterol and LDL-C levels over time (P < .05). Weight
      loss was significantly correlated (P < .001) with the decrease in the total serum
      cholesterol and LDL-C levels for all subjects combined. CONCLUSIONS:
      Hyperlipidemic subjects who were consuming an NCEP Step I diet, with or without
      the incorporation of quick-service meals, experienced a significant decrease in
      their total serum cholesterol and LDL-C levels, body weight, and reported fat
      intake. The beneficial responses in lipid levels were modestly mitigated in the
      quick-service diet group.

PMID- 8572842
TI  - Bowel habit in relation to age and gender. Findings from the National Health
      Interview Survey and clinical implications.
AB  - BACKGROUND: Constipation is widely considered to be a common problem among the
      elderly, as evidenced by the high rate of laxative use in this population. Yet,
      age-related prevalence studies of constipation generally do not distinguish
      between actual alteration in bowel movement frequency and subjective self-report
      of constipation. OBJECTIVE: To determine the relationship between advancing age
      and bowel habit. METHODS: We employed data collected on 42,375 subjects who
      participated in the National Health Interview Survey on Digestive Disorders based
      on interviews with a random nationwide sample of US households. We examined the
      following characteristics reported by this population according to selected age
      groupings by decade: constipation, levels of laxative use, and two bowel
      movements per week or less. RESULTS: Contrary to conventional wisdom, there was
      no age-related increase in the proportion of subjects reporting infrequent bowel
      movements. Nonetheless, the prevalence of self-report of constipation increased
      with advancing age, with a greater proportion of women reporting this symptom
      than men across all age groups. Laxative use also increased substantially with
      aging; while women were more likely to use laxatives than men, this effect
      attenuated with advancing age. A U-shaped relationship was observed between
      advancing age and bowel habit in men and women; 5.9% of individuals younger than
      40 years reported two bowel movements per week or less compared with 3.8% of
      those aged 60 to 69 years and 6.3% of those aged 80 years or older. This
      relationship persisted after adjusting for laxative use. CONCLUSION: These
      findings suggest that a decline in bowel movement frequency is not an invariable
      concomitant of aging. In elderly patients who report being constipated, it is
      essential to take a careful physical, psychological, and bowel history rather
      than to automatically assume the need for laxative use.

PMID- 8572843
TI  - Serologic response to treatment of syphilis in patients with HIV infection.
AB  - BACKGROUND: Much controversy exists concerning the manifestations, therapy, and
      response to treatment of syphilis in patients coinfected with the human
      immunodeficiency virus (HIV). OBJECTIVE: To assess the effect of HIV infection on
      the serologic response to treatment of patients with syphilis. METHODS: Sixty
      four HIV-seropositive patients with syphilis were matched with 64 patients with
      syphilis who were HIV negative. Matching criteria included age (+/- 5 years),
      sex, race, initial rapid plasma reagin (RPR) titer (+/- 1 dilution), and stage of
      syphilis at entry. There were 26 matched patients with early syphilis, 26 matched
      patients with late syphilis, and 12 matched patients with biological false
      positive RPR. The HIV-positive patients with early syphilis received three doses
      of penicillin G benzathine. All other patients received treatment as recommended
      by the Centers for Disease Control and Prevention, Atlanta, Ga. Our study's major
      end points were clinical and serologic response to treatment. RESULTS: All 16
      patients with symptomatic syphilis were cured. No patient developed clinical
      signs of neurosyphilis during the 12-month follow-up period. Twenty-nine (56%) of
      52 HIV-positive patients with early or late syphilis did not have a fourfold
      decrease in RPR titer 6 months after treatment compared with 20 (38%) of 52
      matched controls (P = .06). No unique characteristics identifying patients who
      did not respond serologically could be established. The HIV-positive patients
      with initial RPR less than 1:32 experienced a significantly slower decrease in
      RPR at 12 months than did the controls (P < .001). CONCLUSIONS: Patients with
      syphilis who are HIV positive are less likely to experience serologic improvement
      after recommended therapy than are patients with syphilis who are HIV negative.
      Patients with HIV infection who contract syphilis should receive intensive and
      prolonged follow-up, and consideration should be given to designing alternative
      regimens.

PMID- 8572844
TI  - Patient notification and follow-up of abnormal test results. A physician survey.
AB  - OBJECTIVE: To investigate physician practices in the handling of patients' test
      results from the time the test was ordered until the time any required follow-up
      was completed. METHODS: Survey of 161 attending physicians and 101 residents in
      family practice and internal medicine practicing at a large urban teaching
      hospital and 21 suburban primary care practices in Southeastern Michigan. The
      survey included questions about physician demographics, and whether physicians
      have methods for ensuring that (1) the results of all tests ordered are received,
      (2) all patients are notified of results, (3) all patient notification is
      documented, and (4) all required follow-up is done. Physicians were also asked to
      self-rate the reliability of their methods and the importance of various steps in
      the handling of patients' test results. RESULTS: The response rate was 79% for
      both attending physicians and residents. Approximately 17% to 32% of physicians
      reported having no reliable method to make sure that the results of all tests
      ordered are received. One third of physicians do not always notify patients of
      abnormal results. The most common reasons reported for not notifying patients
      were that the results were trivial and that the patient was expected to return to
      the clinic soon. Residents were significantly less likely to document notifying
      patients of abnormal results (P < .001). Only 23% of physicians reported having a
      reliable method for identifying patients overdue for follow-up. CONCLUSIONS: Lack
      of methods to ensure that the results of tests ordered were received, dependence
      on follow-up visits to inform patients of results, and lack of documentation were
      relatively common among physicians surveyed. These could lead to an increased
      risk of malpractice litigation and suboptimal patient care.

PMID- 8572845
TI  - Microbiology of mediastinitis.
AB  - OBJECTIVE: To study the microbiologic and clinical characteristics of patients
      with mediastinitis. METHODS: Retrospective review of clinical and laboratory data
      of 17 patients treated between 1980 and 1987. RESULTS: Aerobic or facultative
      bacteria only were present in three patients (18%), anaerobic bacteria only in
      seven (41%), and mixed aerobic-anaerobic flora in seven (41%). In total, there
      were 42 isolates, 13 aerobic or facultative and 29 anaerobic bacteria, an average
      of 2.5 per specimen. Anaerobic bacteria predominated in infections that
      originated from esophageal perforation and orofacial, odontogenic, and gunshot
      sources. The predominant aerobes were alpha-hemolytic Streptococcus (three
      isolates), Staphylococcus aureus (two isolates), and Klebsiella pneumoniae (two
      isolates). The predominant anaerobes were Prevotella and Porphyromonas species
      (eight isolates), Peptostreptococcus species (seven isolates), and Bacteroides
      fragilis group (three isolates). CONCLUSION: These data highlight the
      polymicrobial aerobic-anaerobic nature of mediastinitis.

PMID- 8572846
TI  - Rhinocerebral mucormycosis. Therapy with amphotericin B lipid complex.
AB  - Rhinocerebral mucormycosis with intracranial involvement has a high mortality.
      The standard therapy consists of aggressive surgical debridement accompanied by
      high doses of amphotericin B deoxycholate. Even with this therapy, the mortality
      rate has been 48% in the series reported since 1980. We treated a 60-year-old
      diabetic woman with rhinocerebral mucormycosis involving the cavernous sinus
      whose infection responded to medical therapy with amphotericin B lipid complex.
      To our knowledge, this is the only well-documented medical cure of a patient with
      rhinocerebral mucormycosis and intracranial involvement.

PMID- 8572847
TI  - Thyroid hormones and osteoporosis.

PMID- 8572848
TI  - Thyroid hormone use and fractures.

PMID- 8572849
TI  - [Effects of bisoprolol and ramipril on short-term variability of systolic blood
      pressure during mental stress test: spectrum analysis].
AB  - The mid frequency component (MFC = 66-128 mHz) of blood pressure is an index of
      sympathetic vascular control. To investigate the effect of bisoprolol (B) and
      ramipril (R) treatment (TT) on the short-term variability of systolic blood
      pressure (SBP) diastolic blood pressure (DPB) and heart rate (HR) reactivity
      during mental stress, we studied 54 mild essential untreated hypertensive
      patients (24 men, 45 +/- 9.6 years, BP > 160/90 mmHg after a 15-days placebo run
      in period) who were randomly assigned to double blind treatment (B: 10 mg/day: n
      = 28 and R: 5 mg/day: n = 26). A Stroop Word Color Conflict Test (SWCCT) was
      performed before and after 2 months of treatment. Hemodynamic parameters (BP and
      HR) were measured by a non invasive device (Finapres 2300E, Ohmeda-Maurepas) and
      underwent spectral analysis (SBP: mmHg.Hz-1/2, HR: beats/min.Hz-1/2, Anapres 1.2,
      Notocord-Orgametrie Systems, Igny-Lille) at rest and during SWCCT. The
      sympathetic vascular activity was assessed by calculating the area of the mid
      frequency component (MFC = 66-128 Hz). RESULTS: [table: see text] CONCLUSION: The
      absolute variations in sympathetic activity during SWCCT as demonstrated by
      analysis of MFC of SBP and HR is not affected by chronic ramipril treatment,
      whereas bisoprolol attenuates sympathetic reactivity during SWCCT.

PMID- 8572850
TI  - [Therapeutic benefit of a low dose of indapamide: results of a double-blind
      against placebo European controlled study].
AB  - Indapamide is a diuretic prescribed in the treatment of hypertension at the
      dosage of 2.5 mg per day. In accordance with international recommendations
      concerning the need to use low doses of antihypertensives, a new lower-dose form
      of indapamide has been developed to achieve the best safety/efficacy ratio by
      decreasing the incidence of hypokalemia. A new pharmaceutical sustained-release
      (SR) form was developed to give a smooth pharmacokinetic profile in comparison
      with the indapamide instant release (IR) form. The aim of this study was to
      determine the lowest new dosage of the SR form producing similar hypertensive
      efficacy as the LR form, and decreasing the percentage of patients with a serum
      potassium concentration below 3.4 mmol/l. This multicenter study was designed as
      a single-blind, run-in, placebo period of 1 month, followed by a double-blind,
      active treatment period of 2 months, using parallel groups: 285 patients with
      essential uncomplicated mild-to-moderate hypertension (95 mmHg < or = supine
      diastolic blood pressure (sDBP) < or = 114 mmHg) were included and randomly
      treated by either IR indapamide (2.5 mg) or SR indapamide (1.5, 2.0, 2.5 mg).
      After 2 months of active treatment, the one-way analysis of variance on the
      principal criterion (difference in sDBP between M2 and M0) revealed a significant
      treatment effect (p = 0.016). The mean drop in sDBP (+/- standard deviation) was
      5.8 mmHg (+/- 8.6) after 2 months of placebo; 10.1 mmHg (+/- 7.0) after
      indapamide IR 2.5 mg; and 11.0 mmHg (+/- 9.4), 8.9 mmHg (+/- 9.4), and 10.5 mmHg
      (+/- 8.5) after indapamide SR 1.5 mg, 2 mg, and 2.5 mg, respectively. The
      difference between the placebo and indapamide treatment was significant (p < or =
      0.05). No significant difference was detected between the various indapamide
      treatments, i.e., no difference between the IR and SR formulations, no difference
      between the various dosages of the SR form, and therefore no dose/effect
      relationship in the dose interval tested (SR 1.5, 2, and 2.5 mg). The incidence
      of patients with a serum potassium concentration less than 3.4 mmol/l was lower
      with indapamide SR 1.5 mg (11%) than with indapamide 2.5 mg, SR 2 mg, and SR 2.5
      mg, respectively: 29%, 18% and 14%. These results show the interest of a low dose
      of indapamide in improving the safety while producing the same antihypertensive
      efficacy.

PMID- 8572851
TI  - [Effects of short-term treatment with trandolapril on vasodilatator responses
      mediated by receptors or on blood flow in the coronary arteries in SHR].
AB  - The aim of the study was to assess the effects of a one-month treatment period
      with the ACE inhibitor trandolapril (0.3 mg/kg/day) on the endothelial reactivity
      in epicardial right coronary arteries (CA) of 26-30 week-old SHRs. For this
      purpose, segments of CA were mounted in an arteriograph where wall thickness and
      internal diameter (ID) were continuously monitored while intraluminal pressure
      (IP) was controlled. In the absence of flow and under an IP of 30 mmHg, IDs were
      not significantly different in control compared to those of treated SHR arteries
      (microns, 250 +/- 8 vs 240 +/- 7). In preconstricted preparations (5HT, 10
      microns extraluminally) C/E curves were constructed by adding acetylcholine (AC,
      0.01-10 microM) or bradykinin (BK, 0.01-10 microM) in the bath. On the other
      hand, the effect of a stepwise increase in intraluminal flow (50-450
      microliters/min; IP = 30 mmHg) of perfusion solution was observed. The effects of
      subsequent additions of sodium nitroprusside (SNP) were assessed. Maximal
      relaxations were expressed as percent of maximal contractions. Results were as
      follows: [table: see text] These results show that the endothelium-dependent
      relaxation induced by AC and BK were significantly increased in coronary arteries
      of treated compared to control SHRs whereas the flow-induced relaxation seemed to
      remain unaffected in our experimental conditions. From these data, it can be
      concluded that a short period of ACE inhibition in SHRs is able to improve the
      endothelium-dependent vasodilation induced by agonists in the coronary arterial
      bed.

PMID- 8572852
TI  - [Effects of nicorandil, a potassium agonist, on the human umbilical artery. Role
      of the vascular endothelium].
AB  - The umbilical arteries play an important role in the foetal circulation. These
      vessels, which have no sympathetic tone, are a valuable model for the study of a
      direct pharmacological effect on vascular smooth muscle. The aims of this study
      were to determine if the potassium-channel reopener, nicorandil, could relax the
      smooth muscle of the human umbilical artery, if glibenclamide, an inhibitor of
      ATP-dependant potassium channels, can influence the action of nicorandil and,
      finally, to evaluate the role of the vascular endothelium. Rings of human
      umbilical artery 3 mm wide were placed in glycosated, oxygenated (95% O2, 5% CO2)
      Krebs-Henseleit solution, at 37 degrees C, pH 7.4 for isometric myography. The
      rings were contracted with 10(-5) M 5-hydroxytryptamine (5-HT). After
      stabilisation, a dose-effect graph of nicorandil (10(-9) to 3 x 10(-4) M) was
      constructed. In another series of experiments, the rings were incubated with NG
      nitro-L-arginine (NLA) at 10(-4) M, an inhibitor of NO-synthase, for 15 minutes
      and then contracted with 5-HT (10(-5) M) and relaxed with nicorandil at the same
      dosage. In yet another series of experiments, glibenclamide (10(-4) M) was added
      to the bath 15 minutes before contraction with 5-HT (10(-5) M). The vessel was
      then relaxed by incremental doses of nicorandil from 10(-9) to 3 x 10(-4) M.
      During this study, no significant difference was observed with respect to the
      contractions to 5-HT; moreover, the maximal relaxations obtained by nicorandil
      before and after glibenclamide were no significant. On the other hand, only the
      relaxations obtained after incubation with NLA were significant (p < 0.005).
      Furthermore, the pD2 did not differ significantly between the different groups of
      vascular rings. The authors conclude that nicorandil is a powerful dilatator of
      human umbilical artery. Glibenclamide has an inhibitory effect on nicorandil but
      only at low concentrations and in a non-competitive manner. The endothelium seems
      to modulate the vascular tone because relaxation is greater in the presence of an
      inhibitor of NO-synthase: in this type of vessel, the presence of the endothelium
      predisposes to the liberation of contractile factors.

PMID- 8572853
TI  - [Effect of 2 types of diet changes on dietary habits, body weight and cholesterol
      levels in high risk cardiovascular patients].
AB  - Several non-pharmacological interventions such as weight reduction in obese
      subjects or diet alteration in subjects having hypercholesterolemia have been
      shown to be effective in therapeutic trials. Our aim was to test the value of two
      different ways of teaching patients about their diet. From March 1, 1993, to May
      30, 1994, 300 consecutive patients seen in a one-day care hospital were
      randomised into two groups. The 2 inclusion criteria were: 1) body mass index >
      27 kg/m2 in men and > to 25 kg/m2 in women and/or 2) presence of a
      hypercholesterolemia defined by a total cholesterol > 6.5 mmol/l. Patients in the
      first group (C) were educated in a 20 to 50 minutes consultation tailored to
      their needs. Patients in the second group (CC) were given in addition a one-hour
      course about diet. The goal of the diet was to loss at least 3 kg of body weight
      and/or to have a cholesterol value below 6.5 mmol/l without treatment. All
      Patients were followed-up by the same 3 dietician nurses. An out-patient visit
      was planned at 3 months, and a recall letter was sent to the patients who missed
      their appointments. Among the 300 patients, 169 (55%) were seen at the 3-month
      outpatient visit. This proportion did not differ between the 2 groups. Knowledge
      on diet was assessed by the same 33-item self-administered questionnaire. At
      baseline scores were comparable between groups (16 vs 17). Scores improved more
      in the CC than in the C group both at the end of the teaching question (27 vs 23
      in the CC and C group respectively, p < 0.001), and at 3 months (25 vs 23 in the
      CC and C group respectively; p < 0.001). Total cholesterol decreased below 6.5
      mmol/l in 28% of the patients with dyslipidemia and a weight loss > 3 kg was
      observed in 32% of the obese subjects, but improvement did not differ between the
      2 groups. We conclude that a specific one-hour course on diet is able to improve
      knowledge of patients more than a consultation alone, but that better knowledge
      did not result in improved alteration of risk factors at 3 months.

PMID- 8572854
TI  - [Echocardiographic evaluation of left atrial emptying index in hypertension].
AB  - The atrial emptying index (AEI) was used to access the rapid phase of diastolic
      filling of the left ventricle (LV) in 27 hypertensive (HTA) untreated patients
      and in 27 normotensive (N) subjects, matched for age, body, surface and heart
      rate. All the patients had left ventricular hypertrophy (LVH): LV mass index
      (LVmi) > 134 g/m2 for men, 110 g/m2 for women. All subjects had normal systolic
      function by echocardiography. We derived: LV wall thickness (h); antero-posterior
      radius (r); h/r ratio; LVmi; LAmi (before atrial contraction); AEI; A/E ratio.
      RESULTS: [table: see text] The AEI demonstrated a negative correlation with LAvi
      in N (r = -0.49; p = 0.005) and in HTA (r = -0.53; p = 0.002). This index was
      correlated significantly to A/E (r = 0.74; p < 0.001) and to LV mi (r = -0.32; p
      < 0.05 only in HTA. CONCLUSION. In HTA with LVH in comparison with N, there are
      conjointly an increase of the A/E ratio and a reduction of the AEI which is
      considered to be compensated by the increase of LAvi. These data could be
      explained by the less distensibility of LV chamber in relation to LVH.

PMID- 8572855
TI  - [Left ventricular hypertrophy and left atrial morphology in untreated
      hypertensive patients].
AB  - The level of arterial pressure is not the sole determinant of cardiac and
      vascular adaptation to hypertension. In order to identify other factors (such as
      preload) we categorized by echocardiography, 55 never treated hypertensive
      patients and 39 age and gender-matched normal subjects, according to values of
      relative wall thickness and left ventricular mass index. Normal left ventricular
      anatomy was found in 63% hypertensives, whereas among hypertensives 7% had
      "concentric left ventricular remodeling", 16% concentric left ventricular
      hypertrophy and 14% had eccentric left ventricular hypertrophy. Systolic left
      atrial area (LA) was obtained from the four-chamber views. Mitral peak early
      diastolic (E) and late diastolic (A) flow velocity was assessed by Doppler.
      Because clinical characteristics such age and sex differed among the 5 groups
      only results of ANCOVA were reported (means +/- SD). [table: see text] We
      conclude that eccentric left ventricular hypertrophy may be associated with a
      parallel increase of left atrial area. Thus the association of an increase of
      cardiac volume in hypertensive patients with normal diastolic function suggest
      that volume overload may modulate the effect of arterial pressure on cardiac
      morphology.

PMID- 8572856
TI  - [Reproducibility of echocardiographic parameters by automatic detection of
      contours in hypertensive patients].
AB  - The reproducibility of automatic outline detection is a echocardiographic
      reproducibility which has been poorly evaluated in patients with cardiomyopathy.
      Two independent observers identified the systolic surface and mid and end
      diastolic surfaces of 27 hypertensive patients, who had been referred to the
      laboratory for the measurement of left ventricular mass. Each observer examined
      on two occasions all parameters and all parameters were measured at least 2 hours
      apart. The coefficient of variation (CV) expresses the reproducibility of each
      measurement. The intra observer was 10 to 15% and the inter observer 15 to 22%
      for the measurement of surface area. The coefficient of variation is regularly
      greater than 20% for measures of maximum speed, which characterise surface
      changes in diastole. The automatic detection of contours is a echocardiographic
      tool whose potential is great for evaluating left ventricular function but the
      current versions can only be applied to very selective group of patients
      depending on the quality of their echographic window for acoustic quantitation.
      This technique is very operator dependent, in particular as regards setting the
      gains and this explains its poor reproducibility and its limited interest in
      daily clinical practice.

PMID- 8572857
TI  - [Diagnostic value of myocardial thallium stress scintigraphy in the detection of
      coronary artery disease in patients undergoing chronic hemodialysis].
AB  - Atherosclerotic heart disease is the leading cause of death in patients with end
      stage renal disease, but its non invasive detection remains difficult because of
      a low efficacy of exercise testing. The aim of the study was to evaluate
      diagnostic accuracy of thallium myocardial imaging after dipyridamole combined
      with exercise. Forty two chronic dialysis patients (34 men, 8 women) aged 55 +/-
      11 years (range: 36 to 75) without symptom of angina nor myocardial infarction
      were studied. In each patient, an echocardiography, a myocardial scintigraphy
      with dipyridamole combined with symptom-limited exercise, and coronarography were
      performed. A coronary heart disease was diagnosed by coronarography in 10
      patients (4.5 and 1 respectively with 1, 2 and 3 vessels diseased).
      Echocardiography detected a left ventricular hypertrophy (LVH) in 26 patients and
      a regional asynergia in 14 patients. A positive scintigraphy was present in 11
      patients. Three false-positive and 2 false-negative on scintigraphy were noted.
      Sensibility, specificity, positive predictive value and negative predictive value
      were respectively evaluated at 80, 73, 73 and 93%. All the five patients with
      either false-positive or false-negative scintigraphy exhibited a LVH. CONCLUSION.
      In chronic dialysis patients, coronary heart disease may be detected by thallium
      myocardial imaging after dipyridamole combined with exercise.

PMID- 8572858
TI  - [Restoration of normal coronary vasomotricity after intravenous infusion of
      angiotensin converting-enzyme inhibitor (perindoprilat) in hypertensive
      patients].
AB  - We have previously shown that in hypertensive patients, the response of normal
      coronary arteries to sympathetic stimulation evoked by the cold-pressor test
      (CPT), and the endothelial-mediated flow-dependent coronary vasodilation were
      impaired. The immediate effects of the converting-enzyme inhibitor perindoprilat
      (PER) have been evaluated in 10 untreated hypertensive patients with
      angiographically normal coronary arteries and results have been compared to the
      normal responses of 10 control subjects. Diameter changes of proximal left
      anterior descending coronary artery (pLAD) and coronary flow velocity in distal
      LAD have been measured at baseline, during CPT, during recontrol, and after 10 mg
      papaverine (PAP) injection in the mid portion of the LAD. Measures have been
      repeated after intravenous infusion of 1 mg PER, and at the end of the procedure
      after 2 mg intracoronary injection of isosorbide dinitrate (ISDN). Left
      ventricular dimensions and systolic function, total cholesterol, triglycerides,
      HDL and LDL-cholesterol were within the normal range. In hypertensive patients
      before PER, pLAD constricted in response to the CPT and no diameter change was
      observed after PAP, despite the increase in flow velocity in the 2 conditions
      (+63 +/- 27%, and +412 +/- 77%, respectively; all p < 0.001). In control
      subjects, pLAD dilated significantly in these 2 conditions. In hypertensive
      patients after PER, pLAD dilated similarly to control subjects in the 2
      conditions. Endothelium-independent coronary dilation to ISDN was comparable in
      the 2 groups of patients. In conclusion, PER restores a normal coronary response
      both to sympathetic stimulation due to CPT and to flow increase in hypertensive
      patients with angiographically normal coronary arteries and without any other
      coronary risk factors.

PMID- 8572859
TI  - [Coronary artery disease in hypertensive patients: improvement of the diagnostic
      value of exercise test by heart rate adjusted ST segment depression].
AB  - Hypertensive patients complaining of chest pain often have a normal coronary
      angiogram despite a pathological exercise tolerance test. The aim of the present
      study was to establish whether the prevalence of these "false-positive" tests
      could be lowered by adjusting ST segment depression for exercise-induced increase
      in heart rate. METHODS: 60 hypertensive patients, mean age 59 years, with typical
      or atypical chest pain, underwent both a symptom-limited exercise test and a
      coronary angiogram within a median period of 1 day. The ST segment depression was
      measured every 20 ms from the J point. A stepwise discriminant analysis was
      performed: a canonical variable took into account the Detrano index, the
      quantified rate-recovery loop index (QRL index) as well as the presence of a LV
      hypertrophy (Romhilt Estes Score). RESULTS: [table: see text] CONCLUSION: in
      hypertensive patients with chest pain, the specificity and the positive
      predictive value of exercise test are significantly improved by adjusting ST
      segment depression for heart rate both during effort and recovery and by taking
      into account the score of Romhilt Estes on the baseline ECG recording.

PMID- 8572860
TI  - [Paradoxic changes in the morphology of blood pressure wave in hypertensive heart
      diseases].
AB  - The objective is to study the relation between left ventricular (LV) effect
      (index of LV mass (LVMI) and index of inotropic state) and arterial compliance
      determined but the proximal aortic pressure waveform and by the carotid femoral
      pulse wave velocity. MATERIAL: 72 untreated hypertensives; systolic blood
      pressure (SBP) 170 +/- 18 mmHg/diastolic blood pressure (DBP); heart rate: 69 +/-
      9 batt/min; age: 48 +/- 13 years; duration of hypertension 4.6 +/- 4.8 years; sex
      ratio 49 M/23 F. OBJECTIVE: Proximal aortic pressure waveform (carotid artery)
      was studied by applanation tonometry. We derived the index of amplification (AI =
      Pmax-Pinflex)/PP, %), pulse pressure (PP), the maximum rate of rise of pressure
      (dpdt, mmHg.s-1). Echocardiography was used to define the index of LV mass
      (VLMI), end systolic volume (ESV), end systolic stress (ESS), myocardial
      contractile force (ESS/ESV), inotropic state (SBP/ESV). Carotid-femoral pulse
      wave velocity was determined by mechanogram (PWW m/s). RESULTS: 1. Relationship
      of physiological changes of AI and SDA to age, height, PP, DBP, PWV, and LVMI
      were observed in table I (r-Pearson cor. coefficient, * < p 0.05; **: p < 0.001).
      [table: see text] In stepwise regression analysis, even allowing for BP, age, and
      height, there was no relationship between LVMI and the index of aortic
      amplification (AI). 2. In the subjects with LVH (LVMI > 110 g/m2) we found a
      bimodal distribution of the AI which defines two groups in agreement with the
      Murgo Classification. [table: see text] In type B, where AI is weaker, the
      indices of aortic rigidity are reduced, there is an increased ESS and a paradoxal
      fall in LV performances. CONCLUSION: Analysis of proximal aortic pressure
      waveform don't allow to predict index of LV mass. These results suggest that in
      the sphere of LV aortic compiling the reduction of LV function contributes to
      modification of the BP waveform with diminution of dpdt and the index of
      amplification.

PMID- 8572862
TI  - [Coronary artery caliber is not adapted to myocardial oxygen demand in
      hypertensive patients with angiographically normal coronary arteries].
AB  - Resting myocardial oxygen demand and corresponding coronary blood flow are main
      determinants of large coronary artery dimensions in humans. To examine the
      adaptation of epicardial coronary arteries to the increased myocardial oxygen
      demand, myocardial blood flow, in hypertensive patients, diameters of proximal
      and distal left anterior descending coronary artery (pLAD and dLAD), and proximal
      circumflex artery (CX) were determined in 15 untreated hypertensive patients and
      in 10 control subjects by quantitative angiography. All patients had total
      cholesterol < or = 5.40 mmol/l, LDL-cholesterol < or = 3.35 mmol/l, and
      angiographically normal coronary arteries. Measurements were made at base and
      after 2 mg intracoronary isosorbide dinitrate (ISDN) in order to obtain maximal
      dimensions of vessels. Coronary flow velocity was measured in distal left
      anterior descending coronary artery by Doppler. Results show that despite higher
      rate-pressure product in hypertensive patients, the diameters of the coronary
      segments were similar in control subjects and in hypertensive patients at base
      (3.53 +/- 0.84 vs 3.76 +/- 0.48 mm for pLAD; 2.55 +/- 0.50 vs 2.49 +/- 0.52 mm
      for dLAD; 2.92 +/- 0.40 vs 2.78 +/- 0.83 mm for CX, respectively). After
      intracoronary ISDN, diameters were also comparable between the 2 groups (4.54 +/-
      0.86 vs 4.58 +/- 0.60 mm for pLAD; 3.35 +/- 0.58 vs 3.22 +/- 0.61 mm for dLAD;
      3.47 +/- 0.56 vs 3.53 +/- 1.01 mm for CX, respectively). Conversely, coronary
      flow velocity was significantly higher in hypertensive patients at base (10.72 +/
      2.20 vs 6.48 +/- 2.01 cm/s; p < 0.001) and after ISDN (6.59 +/- 2.62 vs 3.72 +/-
      0.87 cm/s; p < 0.001). Despite an elevated myocardial oxygen demand, large
      coronary artery dimensions are not increased in hypertensive patients resulting
      in an elevated coronary flow velocity that may increase longitudinal shear stress
      at the endothelial surface. This might be an important determinant in the
      pathogenesis of atherosclerosis in hypertensive patients.

PMID- 8572861
TI  - [Effect of chronic inhibition of nitric oxide synthesis on vascular structure:
      remodeling or growth?].
AB  - Nitric oxide is an important regulator of vascular tone, as evidenced by the
      marked increase in blood pressure produced by the inhibition of its synthesis.
      Furthermore, nitric oxide may be implicated in the modulation of vascular growth,
      although in vitro and in vivo studies have provided conflicting results. The aim
      of this study is to determine the effects of chronic nitric oxide synthase
      inhibition, with or without antihypertensive treatment, on the structure of the
      basilar artery in the rat. Rats were treated for 6 weeks with N omega-nitro-L
      arginine methyl ester (L-NAME, 50 mg/kg/day) alone or in combination with
      verapamil (100 mg/kg/day) or with trandolapril (1 mg/kg/day). Untreated rats
      served as controls. The structure of perfused and pressurized basilar arteries
      were analyzed in vitro using a video dimension analyzer. Chronic L-NAME treatment
      increased systolic arterial pressure (229 +/- 5 vs 147 +/- 3 for controls; p <
      0.05) and the media to lumen ratio of the basilar artery (0.22 +/- 0.02 vs 0.15
      +/- 0.01 for controls; p < 0.05). This structural alteration was mainly due to
      remodeling (remodeling index: 76%), but not to growth (growth index: 8%, NS). The
      concomitant administration of verapamil and trandolapril prevented the increase
      in blood pressure (154 +/- 6 and 146 +/- 5 mmHg, respectively) and the structural
      changes produced by L-NAME (Media/lumen ratio: 0.15 +/- 0.01 and 0.14 +/- 0.01
      mmHg, respectively). In fact, a positive correlation was observed between the
      media to lumen ratio and the systolic arterial pressure (r = 0.6; p < 0.001). The
      effect of the two antihypertensive treatments, as well as the correlation between
      the wall to lumen ratio and the arterial pressure, suggest that the remodeling of
      the basilar artery depends mainly on the elevation of arterial pressure with
      little contribution of the L-arginine pathway. Furthermore, the very small and
      non significant increase in the cross-sectional area of the basilar arteries from
      L-NAME-treated rats (growth index of 8%), suggest that nitric oxide does not play
      an important role in the modulation of normal cerebral vascular growth in vivo.

PMID- 8572863
TI  - [Role of nitric oxide in the regulation of the mechanical properties of
      peripheral muscular arteries in man].
AB  - Although several experiments have demonstrated the existence of a basal NO
      dependent vasodilatory tone at the arteriolar level, the contribution of NO to
      the mechanical properties of large arteries has not been investigated in humans.
      To evaluate the effect of NO-synthase inhibition on these mechanical properties,
      radial artery internal diameter (d, mm) and wall thickness (h, mm) were measured
      continuously in 11 healthy volunteers (age: 24 +/- 1 years), using an A-mode echo
      tracking system coupled to a Doppler device for the measurement of radial blood
      flow (RBF, ml/min). A catheter was inserted in the brachial artery for
      measurement of arterial pressure (AP, mmHg), and infusion of the inhibitor of NO
      synthesis NG-monomethyl L-arginine (L-NMMA: 4 mumol/min for 5 min, infusion rate
      0.8 ml/min). Arterial compliance C, 10(-3) mm2/mmHg), distensibility (D, 10(
      3)/mmHg), mid-wall stress (sigma, 10(5) dynes/mm2) and incremental modulus (Ei,
      10(7) dynes/mm2) were calculated before and after L-NMMA. After L-NMMA, RBF
      decreased from 31 +/- 6 to 23 +/- 4 (p < 0.05), radial vascular resistance
      increased from 2.70 +/- 0.35 to 3.77 +/- 0.55 (p < 0.05), without changes in AP
      or heart rate. Table shows mechanical parameters, assessed at fixed AP (80 mmHg)
      (*: p < 0.05 vs baseline): [table: see text] Thus, the L-NMMA-induced decrease in
      radial arterial wall stiffness (Ei) without changes in arterial diameter or
      stress demonstrates that NO-synthase inhibition induces an isometric relaxation
      of vascular muscle cells, which explains the increase of arterial compliance at
      constant mid-wall stress. These results demonstrate that NO contributes to the
      regulation of peripheral muscular arterial mechanics in humans. At the level of
      large arteries, the isometric relaxation observed after NO-synthase inhibition is
      probably the consequence of compensatory vasodilator mechanisms.

PMID- 8572864
TI  - [Nephro-angiosclerosis in the graft: impact on graft survival. Study of 33
      cases].
AB  - When early kidney transplant biopsies showed benign hypertensive nephrosclerosis,
      i.e. hyalin arteriosclerosis and/or interlobular arteries intimal thickening,
      they are thought to be of donor origin. Between 1987 and 1992, 439 cadaveric
      renal transplantations have been performed in our department: amongst them 97,
      i.e. 22% patients underwent a graft biopsy before the end of the first post
      transplant month (13 +/- 9.5 days). To ascertain if findings of early renal
      biopsy was predictive of eventual clinical outcome we analyzed renal function and
      blood pressure (BP) in the short and mid term. Nephrosclerosis lesions were found
      in 33 cases (group I) and were absent in the remaining 64 cases (group II). The 2
      groups were not statistically different according to the time on dialysis, the
      recipient's age, the HLA matching, the cold ischemia time. The only statistically
      significant difference was the donor's age: 39.1 +/- 7 years in group I vs 26.9
      +/- 8 years in group II (p = 0.0001). Delayed graft function was not different in
      the 2 groups (13 +/- 9 days group I vs 11 +/- 6 days group II). On the other
      hand, 30% of group I, patients required hemodialysis (9.8% in group II; p <
      0.005). The incidence in graft rejection episodes was similar in both groups
      (50%) as well as surgical complications. Renal function was assessed by
      creatinine clearance at 1 and 2 years and at last follow-up visit (mean follow
      up: 50.5 +/- 44 months in group I and 46.9 +/- 24 months in group II; p = Ns): it
      was similar in both groups (see table). The prevalence of hypertension (HTA) was
      significantly higher in group I than in group II at two years and last follow-up
      (*: p < 0.005). [table: see text] CONCLUSIONS: The age of donor is of importance
      in determining nephrosclerosis of the graft observed on early biopsies. Donor
      related nephrosclerosis is a risk factor for the recipient of developing HTA
      without impairment of graft function in the mid term. In the context of early
      nephrosclerosis, the occurrence of acute rejection episode(s) is detrimental for
      the graft function.

PMID- 8572865
TI  - [Evaluation of spiral computed tomography of the renal arteries alone or combined
      with Doppler ultrasonography in the detection of renal artery stenosis.
      Prospective study of 114 renal arteries].
AB  - A renovascular etiology occurs in 0.2 to 2% of hypertensive patients. Recently,
      spiral computed tomography (CT) has evolved as a new minimally invasive tool for
      the diagnosis of vascular pathologic conditions. The purpose of this study was to
      compare both spiral CT and color Doppler ultrasonography (US) with intraarterial
      digital subtraction angiography (DA) in the detection of renal artery stenosis
      (RAS) in hypertensive patients. Between December 1993 and April 1994, 44
      hypertensives (men 22, mean age 52 years) suspected secondary hypertension were
      prospectively studied with spiral CT (Somatom Plus S, Siemens) US (Acuson, 3.5
      MHz probe) and DA (double-blind evaluation). DA visualized 11 significant (> 50%)
      stenoses (11/114 renal arteries, including 27 accessory). On spiral CT, 9/11 were
      detected and 2 additional stenoses considered false positive. On US 5 stenoses
      were detected whereas 11 were demonstrated by DA; 2 patients had false positive
      US results. [table: see text] We conclude that combined spiral CT and color
      Doppler ultrasonography is an effective and relatively non invasive alternative
      to intraarterial digital angiography for the detection of renal artery stenosis
      in a hypertensive population screened for renovascular hypertension.

PMID- 8572866
TI  - [Comparison and reproducibility of 4 methods of indirect blood pressure
      measurement in moderate hypertension].
AB  - The measurements and the reproducibility of ambulatory, home, clinic and repeated
      non ambulatory automatic blood pressure (BP) were compared in 16 patients (45 +/-
      11 yrs) with mild untreated hypertension (BP: 164 +/- 12/101 +/- 6 mmHg at the
      selection visit); 26 +/- 19 days after this visit, each patient had two sets of
      BP measurements in 4 different ways taken 2 weeks apart under similar study
      conditions: daily ambulatory recordings (ABP), home self-measurement readings
      (over 5 days) (HBP), 2-minute repeated automatic BP measurements during the 20
      minutes preceding the physician examination (RABP) and clinic BP (CBP) with a
      standard sphygmomanometer mercury column. The reproducibility was assessed by
      standard deviation of the differences (SDD). Decisions to treat the patients were
      made according to the results obtained by CBP (BP > 140/90 mmHg during the
      selection visit and the 2 study visits), by the first ABP (mean BP > 139/87 mmHg)
      and by the first week of HBP (mean BP > 127/83 mmHg) were compared; the outcome
      of these three procedures was then compared. RESULTS: [table: see text]
      CONCLUSION: Repeated automatic and clinic BP were higher than ambulatory and home
      BP. Reproducibility of ambulatory and home BP were comparable and better than
      clinic or repeated automatic BP. The percentage of decision to treat according to
      the results of clinic, home and ambulatory BP was comparable but they were not
      the same patients who were treated with the 3 methods.

PMID- 8572867
TI  - [Comparison of different methods in the assessment of the ratio of hypertensive
      patients responding to antihypertensive treatment].
AB  - Identification of a responder to an antihypertensive treatment is helpful and
      also very difficult in an open uncontrolled study. The existence of many
      arbitrary methods to define a responder, the placebo effect and the regression to
      the mean phenomenon coexist and give spurious interpretation. We analysed an open
      study recruiting 6,530 hypertensive patients (DBP > or = 95 mmHg at entry),
      treated with the same antihypertensive drug during 3 months. Mean initial and at
      3 months blood pressures were respectively 178/101 mmHg and 151/86 mmHg. We
      observed significant variation in the % of responders (20 to 80%) to a drug when
      applying different methods. Placebo effect and regression to the mean lead to an
      overestimation. Without a placebo controlled design, we suggest to increase the
      BP level for inclusion to determine the % of responders with the standard goal
      pressure (DBP < 90 mmHg) and to use Oldham's method for adjusting for the
      regression to the mean unless the coefficient of correlation found is around zero
      and if upper level of DBP is not selected for inclusion.

PMID- 8572868
TI  - [Ambulatory blood pressure monitoring and clinical trials].
AB  - Ambulatory blood pressure monitoring (ABPM) is now widely used for the assessment
      of antihypertensive drugs. This procedure may be used in phase II studies in dose
      ranging evaluations as well as in phase III in order to assess the drug efficacy
      in the patient's natural environment. The increase in the reproducibility related
      to the repetition of blood pressure measurements by ambulatory monitoring may
      improve the accuracy of the trial and minimize the numbers of subjects required.
      Placebo fails to lower ambulatory blood pressure in almost all studies.
      Nevertheless, placebo is always necessary in clinical studies with ABPM at least
      for the pre-inclusion phase and in order to study the peak-trough ratio. This
      ratio may be accurately assessed by ABPM. Finally, ABPM may be useful to rule out
      "white coat" responders, who are not really hypertensive patients.

PMID- 8572869
TI  - [Quality of blood pressure control in general practice and in the HOT study.
      French Research Group HOT (Hypertension Optimal Treatment)].
AB  - A previous investigation of the French League against Hypertension has shown that
      only 27% of the hypertensives aged below 64 years and 19% of those aged above 64
      years have their BP controlled under treatment (BP < 140/90 mmHg). The
      international, prospective, randomised HOT study aims at assessing the optimal
      diastolic BP (DBP) level during active antihypertensive treatment to reduce at
      the best the cardiovascular morbidity and mortality. The study is on-going, with
      a completion of inclusions. The BP measurements are performed by oscillometric
      method with the D2 international BP device, HESTIA. At enrollment, only 52% of
      the hypertensives were treated, their mean BP level being 161/99 mmHg +/- 18/9
      mmHg (n = 10,005). On randomisation, two weeks after the treatment withdrawal, BP
      was 170/106 +/- 15/4 mmHg. Six months later, under treatment, BP was 150/84 +/-
      10/7 mmHg with a mean decrease of 11/15 mmHg compared to values under previous
      treatment. Depending on the randomisation groups which are defined by different
      DBP objectives, 87.5 to 92.2% of the patients have a BP normalisation (DBP < or =
      90 mmHg) after one year of treatment. Five explanations may be proposed for the
      better BP control observed in the study compared to the results at inclusion,
      reflecting the general practice: (1) the fact that the patient is free to
      participate and has been informed may have improved the compliance, (2) the
      patient's follow-up was reinforced during the first weeks, (3) the protocol is
      based on the treatment initiation by a dihydropyridine with a long duration of
      action: felodipine, (4) the BP objectives are rigorously defined by a DBP between
      80 and 90 mmHg depending on the randomisation group whereas in general practice,
      the physician may have a smoother objective mainly aiming at improving
      tolerability, (5) the larger use of a bi-therapy. CONCLUSION. The more ambitious
      aims of BP control (DBP < or = 90, 85, 80 mmHg) in this study have induced a
      treatment intensification with a better BP control.

PMID- 8572870
TI  - [Resistant arterial hypertension].
AB  - The aim of the study was to determine the prevalence of resistant hypertension in
      our unit and the frequency of its various causes. Of the 890 patients seen for
      the first time between January 1, 1993, and June 30, 1994, 257 were referred for
      hypertension. Of the 62 (24.1%) patients referred for "resistant hypertension",
      only 25 met our criteria for resistance: blood pressure > or = 160 and/or 95 mmHg
      on the first visit to us without "white-coat" effect and at least two additive
      antihypertensive drugs at optimal doses. Of the 195 patients referred for other
      reasons, 10 met our criteria for resistance. Thus, the prevalence of resistant
      hypertension is 13.5%. A cause of resistant hypertension was found in 50% of the
      patients referred for resistant hypertension, in 72.2% of the patients who met
      our criteria for resistance and in 84% of the patients referred for resistant
      hypertension and who met our criteria for resistance.

PMID- 8572871
TI  - [Future of blood pressure in young adults during a 15-year follow-up].
AB  - Tracking of BP and their determinants were investigated among 2,752 young adults,
      aged 20-35 years (1,209 men and 1,543 women) in a longitudinal study conducted
      since 1974 at the Center for Preventive Medicine in Nancy-Vandoeuvre. Prevalence
      of hypertension (BP > 160/95 mmHg or hypertensive drugs) rose over 15 years from
      2.1% to 6.8%. Subjects with antihypertensive drugs were about 3.5% after 15 years
      of follow up (mean age at the fourth examination: 44 years). Coefficients
      correlation between initial BP and BP at 5, 10 and 15 years were 0.43, 0.38 and
      0.35 for systolic BP, 0.28, 0.24 and 0.26 for diastolic BP in population without
      antihypertensive drugs. The part of variance for BP at the fourth examination
      explained by variables from previous examinations was low (27% for systolic BP
      and 13 or 17% according to sex for diastolic BP). The main variable in the
      regression was always the BP at the third examination; 69.3% of subjects with
      high BP (> 140/90 mmHg or treated for hypertension) were well classified in a
      discriminant analysis. These results underline the difficulty to predict BP and
      hypertension in a general population, suggest to take into account pathogenic
      predictors in further studies and allow us to propose selective prevention of
      future hypertensive.

PMID- 8572872
TI  - The nigrostriatal dopamine system and the development of hypertension in the
      spontaneously hypertensive rat.
AB  - Several observations reported in the literature reveal a role of brain
      catecholaminergic systems in the development of hypertension in spontaneously
      hypertensive rats (SHR). As reviewed here, our results obtained with
      intracerebroventricular injections of 6-hydroxydopamine in your SHR point in
      particular to the involvement of the nigrostriatal dopamine system. The
      electrically stimulated release of radiolabeled dopamine in vitro from caudate
      nucleus slices of SHR was lower than that in slices of normotensive Wistar-Kyoto
      rats (WKY). Using an in vivo microdialysis method, we found that the
      extracellular concentration of dopamine and the metabolite DOPAC was lower in the
      caudate nucleus of conscious SHR than in that of WKY. We also studied the effects
      of lesions of the pars compacta of the substantia nigra of 4 week-old SHR and
      WKY, 1) on blood pressure and heart rate, 2) on the concentrations of dopamine
      and metabolites in the caudate nucleus and 3) on the release of radiolabeled
      dopamine from caudate nucleus slices using an in vitro superfusion method, 6
      weeks following lesioning. Substantia nigra lesions caused a profound attenuation
      of the development of hypertension in SHR, with no effect on heart rate. The
      ratios DOPAC/dopamine and HVA/dopamine were lower in sham-treated SHR than in
      sham-treated WKY pointing to a lower turnover of dopamine in SHR. Six weeks after
      lesioning, the concentrations of dopamine were decreased in the caudate nucleus
      of both strains. At this time, the stimulus-evoked release of dopamine from the
      remaining terminals was significantly increased in caudate nucleus slices of SHR
      but not in slices of WKY. Thus, whereas the release of dopamine from caudata
      nucleus slices is lower in sham-treated SHR than in sham-treated WKY, lesioning
      of the substantia nigra results in a similar release of dopamine from caudate
      nucleus slices of lesioned SHR and sham-treated WKY. This normalization of
      dopaminergic activity may be the causal factor underlying the attenuation of the
      development of hypertension in SHR after bilateral lesioning of the pars
      compacta, of the substantia nigra.

PMID- 8572873
TI  - [Non-hypertensive desoxycorticosterone treatment enhances the progression of
      atherosclerosis in WHHL rabbit].
AB  - Coexistence of hypertension and lipid disorders enhances the development of
      atherosclerosis. However it is still unclear whether this promoting effect of
      hypertension results only from hemodynamic changes or whether part of it is
      mediated by humoral or neurogenic factors independently of blood pressure
      alteration. The aim of this study is to determine whether mineralocorticoids,
      which are known to be involved in the pathogenesis of hypertension, can influence
      the atherosclerotic process in Watanabe heritable hyperlipidemic rabbits (WHHL)
      independently of pressure changes. For this purpose, DOCA (200 or 400 mg/kg) or
      vehicle were implanted subcutaneously for 4 weeks in 3 months old WHHL or New
      Zealand (NZ) rabbits, without nephrectomy and with a fluid intake solution of 1%
      NaCl +0.2% KCl. DOCA treatment, independently of hemodynamic changes,
      significantly increases the size of atherosclerotic lesions in parallel with the
      aortic cholesterol esters content in the arch and thoracic aorta of WHHL rabbits.
      Plasmatic and aortic cholesterol and triglyceride content remains unchanged by
      DOCA treatment. Alteration of endothelial function usually found in WHHL rabbits
      is accentuated only for the dose of 400 mg/kg. Aortic sensitivity to serotonin is
      not altered, but the maximal contraction to this agonist is decreased in both
      strains by mineralocorticoid treatment. These results indicate the importance of
      non-hemodynamic factors related to hypertension which are implicated also in
      atherogenesis and support the clinical observations that a reduction of arterial
      pressure in hypertensive atherosclerotic patients is not sufficient to reduce the
      progression of this vascular disease.

PMID- 8572874
TI  - [Hormonal contribution to short-term variability of blood pressure in a
      renovascular hypertension model].
AB  - Spectral analysis was recently chosen to characterize the fast oscillations
      depending on the autonomic nervous system. Humoral stimuli could impinge on low
      frequency (LF) domain of blood pressure (BP) since the time lag to humoral
      systems activation is larger. This study was designed to analyse LF components of
      short-term variability of BP of conscious rats in conditions where humoral
      systems were activated. We studied rats with two-kidney Goldblatt hypertension in
      which the BP level was dependent upon the renin-angiotensin and kallikrein-kinin
      systems. Spectral powers of the systolic and diastolic BP and heart rate (HR)
      were computed in the high (respiratory, HF), mid (0.2-0.6 Hz, MF) and low (0.02
      0.2 Hz, LF) frequency bands, as detected by the Fast Fourier Transform technique
      on consecutive 102-s stationary periods. Renal hypertension by a two-kidney one
      clip procedure was associated with a marked rise in SBP (+47 mmHg) and no
      significant change in HR. Renal hypertension selectively increased the LF
      component of SBP (+86%) when hypertensive rats were compared to sham operated
      animals. First, administration of losartan, a selective nonpeptide angiotensin II
      receptor antagonist, to sham rats resulted in a moderate SBP decrease, a
      significant tachycardia (+47 batt/min) with no change in BP and HR spectra
      profiles. Losartan determined in the hypertensive group a marked fall in SBP (-25
      mmHg) with a significant tachycardia (+50 batt/min). Interestingly, losartan
      reduced the LF component of SBP (-26%). In a second series of normotensive and
      hypertensive rats, Hoe 140, a bradykinin B-2 receptor antagonist, did not affect
      the BP and HR levels of the two groups of rats. Hoe 140 decreased the LF
      component of SBP variability (-28%). Losartan, added after Hoe 140, decreased the
      BP (-17 mmHg) in association with a tachycardia (+59 batt/min) and induced a
      supplementary decrease of the LF component of SBP variability (-60%) in
      hypertensive rats. After the combined blockade, the LF component of SBP of the
      hypertensive rats was equivalent to that of the sham rats. Thus, an increase in
      the LF component of BP variability was observed in a model of hypertension where
      the BP is dependent upon humoral factors. The contribution of the renin
      angiotensin and kallikrein-kinin systems in the slow fluctuations of BP was
      demonstrated using two specific antagonists losartan and Hoe 140.

PMID- 8572875
TI  - [Absence of the effect of nitric oxide on pulmonary and systemic hypertension
      induced by sino-aortic denervation].
AB  - Inhaled nitric oxide, a selective pulmonary vasodilator, reverses hypoxic
      pulmonary vasoconstriction and is an effective treatment in some cases of human
      pulmonary hypertension. Localization of nitric oxide synthase had indicated a
      neural role for nitric oxide. Thus, we studied the interactions between inhaled
      nitric oxide and systemic and pulmonary vascular reactivity in acute neurogenic
      hypertension. In 6 male beagle dogs (mean weight: 15 +/- 1 kg), anesthetized by
      chloralose (8 cg/kg) and in spontaneous ventilation, the hemodynamic effects on
      systemic and pulmonary circulation of inhaled nitric oxide (12 ppm) were studied
      before and after acute sino-aortic denervation. The hemodynamic effects of
      intravenous propranolol (300 micrograms/kg) were studied after denervation. Mean
      arterial pressure (MAP), pulmonary capillary pressure (PCP), mean arterial
      pulmonary pressure (MAPP), cardiac input (CI) and oxygen venous saturation (SvO2)
      were measured. [table: see text] Sino-aortic denervation causes an acute and
      transitory pulmonary hypertension due to a double mechanism: a post-capillary
      hypertension (increase PCP) secondary to an increase left ventricular post-charge
      by systemic hypertension and a precapillary hypertension. In fact, vascular
      pulmonary resistances increase from 1.8 +/- 0.1 to 3.4 +/- 0.8 uW after
      denervation (p < 0.05). Change in pulmonary vascular reactivity induced by
      catecholamines is probably involved. Propranolol but not inhaled nitric oxide
      reverse pulmonary hypertension due to sino-aortic denervation.

PMID- 8572876
TI  - [Demonstration of a vasopressor role of endogenous endothelin after inhibition of
      nitric oxide synthesis in rats].
AB  - Although it is clear that vascular endothelial cells synthesize and release
      endothelin (ET), the contribution of this vasconstrictor peptide to the
      regulation of vascular tone appears limited in normal conditions. One possibility
      to explain this moderate effect is that continuous production of nitric oxide
      (NO) may permanently inhibit the release and the vasoconstrictor effects of ET.
      In these conditions, inhibition of NO synthesis might unmask a vasopressor
      response to ET. Thus, we tested whether bosentan (3 mg/kg i.v.), a non-peptide
      antagonist of ETA and ETB receptors, or BQ-123 (3 mg/kg), an antagonist of ETA
      receptors, affected the hypertensive response induced by the NO synthase
      inhibitors NG-nitro-L-arginine methyl ester (L-NAME 3 mg/kg) or NG-nitro L
      arginine (3 mg/kg) in anesthetized, normotensive rats. Bosentan or BQ-123 did not
      affect blood pressure. L-NAME significantly increased mean arterial pressure (%
      increase from baseline: 25 +/- 5%), and this was reduced by bosentan (13 +/- 3%;
      p < 0.05) or by BQ-123 (14 +/- 5%; p < 0.01). In contrast, bosentan did not
      affect the pressor response to phenylephrine. The response to L-NAME (3 mg/kg)
      was also reduced by bosentan in ganglion-blocked (chlorisondamine: 2.5 mg/kg;
      controls 89 +/- 10; bosentan: 45 +/- 7%) or pithed rats (controls: 165 +/- 9;
      bosentan 85 +/- 12%; p < 0.01). Bosentan also inhibited the pressor response to
      NG-nitro L-arginine (3 mg/kg-1) in normal (controls 24 +/- 5, bosentan 10 +/- 3%;
      p < 0.01) or ganglion-blocked rats (controls 86 +/- 13; bosentan 25 +/- 8; p <
      0.01). Finally, L-NAME induced a modest increase in plasma levels of ET-1
      (controls: 26.8 +/- 4.1; L-NAME: 38.5 +/- 3.3 pg/ml; p < 0.05). Thus, acute
      inhibition of NO synthesis unmasks a tonic vasopressor influence of ET.

PMID- 8572877
TI  - [Hemodynamic effects of sub-chronic NO synthase inhibition in conscious dogs:
      role of EDRF/NO in muscular exertion].
AB  - Acute and chronic administration of nitric oxide (NO) synthase (NOS) inhibitors
      increase mean arterial blood pressure (MAP) in rats but their hemodynamic effects
      in other species remain unknown. Moreover, the role of NO in the control of
      exercise-induced vasodilation is still debated. To answer these questions, six
      dogs were instrumented for the continuous measurement of cardiac output (CO,
      electromagnetic flow probe on the aorta), MAP (aortic catheter) and left
      ventricular pressure (Konigsberg gauge). Total peripheral resistance (TPR) was
      calculated as MAP/CO ratio and dP/dt was used as an index of cardiac inotropism.
      The dogs were treated from day 0 (D0) to 7 (D7) by the NOS inhibitor, N omega
      nitro-L-arginine (L-NNA), 20 mg/kg/day (IV). Such a dose regimen resulted in NOS
      inhibition evidenced (a) in vivo by a reduction of the hypotensive responses to
      graded doses of acetylcholine and bradykinin, (b) ex vivo by a decrease in the
      relaxation of the femoral artery to acetylcholine (EC 50 = 2.2 +/- 0.6 10(-7) M
      after L-NNA vs 2.2 +/- 0.8 10(-8) M in controls). One month after
      instrumentation, the dogs being conscious, MAP measured at rest remained
      unchanged following one week L-NNA treatment (from 90 +/- 2 at D0 to 91 +/- 5
      mmHg at D7). However, TPR increased (from 3,600 +/- 290 at D0 to 6,300 +/- 510
      dyn.s.cm-5 at D7) and CO decreased (from 2.1 +/- 0.2 at D0 to 1.2 +/- 0.1 l/min
      at D7) (all p < 0.01), partly as the result of a marked bradycardia (from 100 +/-
      7 at D0 to 60 +/- 7 beats/min at D7). L-NNA induced-increase in TPR was
      completely reversed by a bolus injection of nitroglycerin (10 micrograms/kg).
      During treadmill exercise (12 km/h), heart rate (251 +/- 9 at D0 vs 226 +/- 11
      beats/min at D7), CO (6.3 +/- 0.9 at D0 vs 4.3 +/- 0.7 l/min at D7) and stroke
      volume remained significantly lower, and TPR significantly higher (1,662 +/- 278
      at D0 vs 2,621 +/- 489 dyn.s.cm-5 at D7) after L-NNA than in the control state.
      Thus, NOS inhibition in resting conscious dogs by L-NNA markedly increases
      peripheral resistance but does not increase arterial pressure. In addition, L-NNA
      blunts both exercise-induced peripheral vasodilation and increase in cardiac
      output, despite metabolic vasodilation.

PMID- 8572879
TI  - [Evidence for two alpha 2B-adrenoreceptor isoforms in the renal cortex of salt
      sensitive and salt resistant Sabra rats. Effect of salt loading].
AB  - alpha 2-adrenoceptors are involved in various renal functions regulating blood
      pressure. They were classified in subtypes whom genes were identified in both
      humans and rats. In rat renal cortex it was evidenced that the alpha 2B isoform
      is predominant. This result was confirmed in Sabra rats. However, the renal
      cortex alpha 2B density is higher in salt-sensitive (SBH) than in salt-resistant
      (SBN) Sabra rats. alpha 2B-adrenoceptors were recently subclassified in two
      pharmacologically distinct subtypes exhibiting high and low affinity for
      guanoxabenz and respectively called alpha 2B1 and alpha 2B2. We studied sodium
      loading effect on alpha 2B1 and alpha 2B2 distribution in Sabra rat renal cortex
      using competition experiments between [3H]-yohimbine and guanoxabenz. The rats
      were submitted to normal (0.2%) or high sodium diet (8%) for six weeks. Under
      normal diet, proportion alpha 2B1 and alpha 2B2 was similar in SBH and SBN.
      Nevertheless, their respective densities were significantly higher in SBH as
      compared to SBN (alpha 2B1: 90.6 +/- 4.1 vs 57.4 +/- 2.5 fmoles/mg prot, p <
      0.0001; n = 5; alpha 2B2: 102.7 +/- 4.0 vs 66.4 +/- 4.6 fmoles/mg prot; p <
      0.0001; n = 5). Under high sodium diet the distribution of these two isoforms was
      altered. The densities of alpha 2B1 were decreased by 27.0 +/- 5.9% in SBH (68.0
      +/- 4.0 fmoles/mg prot; p < 0.0001, n = 5) and by 47.3 +/- 7.4% for SBN (29.2 +/-
      3.1 fmoles/mg prot; p < 0.0001; n = 5). Conversely, the densities of alpha 2B2
      were increased by 28.3 +/- 5.4% in SBH (131.1 +/- 9.5 fmoles/mg prot; p < 0.001;
      n = 5) and by 75.0 +/- 17% in SBN (123.2 +/- 9.1 fmoles/mg prot; p < 0.0001; n =
      5). In conclusion, alpha 2B1- and alpha 2B2-adrenoceptor subtypes are found in
      renal cortex of both SBH and SBN. Our data demonstrated an equal distribution of
      these two isoforms between SBH and SBN under normal salt diet. This distribution
      is largely altered, especially in SBN, by the high sodium diet. From these
      modifications might result differential renal responses to activation of alpha 2B
      adrenoceptors between SBH and SBN, and consequently responsible for normal or
      high blood pressure after high sodium diet.

PMID- 8572878
TI  - [Chronic and acute effect of cycletanine in NO-dependent hypertensive pregnant
      rats].
AB  - Decreased response to vasopressor agents characterizes pregnancy. Endothelium
      derived relaxing factors and vasodilating prostaglandins play an important role
      in the vascular tone during pregnancy. Since inhibition of nitric oxide (NO)
      biosynthesis induced by NO2-arginine enriched diet produced hypertension we
      measured in vivo cardiovascular responses to PGF2 alpha, L-arginine (L-arg) and
      cicletanine (Cic, IPSEN, France) which enhances PGI2 production. From day 13 to
      day 20 of gestation 4 groups of female Wistar rats were fed NO2-arg (31 mg/kg/d),
      NO2-arg+Cic (10 mg/kg/d), Cic enriched or control diet (C). Mean arterial
      pressure (MAP) was measured via a carotid catheter in anesthetized rats.
      Injection of PGF2 alpha (50 micrograms/kg) in jugular vein significantly
      increased MAP in the NO2-arg group versus, NO2-arg+Cic, Cic and C group (+23.5 +/
      3.3 vs +15.7 +/- 2.2, +15.8 +/- 2.2 and +17 +/- 1.85 mmHg; p < 0.01). Injection
      of L-arg (100 mg/kg) or Cic (1 mg/kg) 5 min before PGF2 alpha produced no
      modification in MAP in C and Cic group. Likewise in NO2-arg group injection of L
      arg or Cic produced a diminished pressor response to PGF2 alpha (+23.5 +/- 3.3 vs
      -17.5 +/- 1.7 mmHg; p < 0.05 and +15.2 +/- 2.4 mmHg; p < 0.01 respectively). In
      NO2-arg+Cic group, only injection of Cic induced a diminished pressor response to
      PGF2 alpha which is more important without L-arg (+15.7 +/- 2.2 vs +9.1 +/- 1.3
      mmHg; p < 0.001) or with L-arg (+13.6 +/- 1.5 vs +9.1 +/- 1.3 mmHg; p < 0.01).
      Cicletanine also significantly diminished the proteinuria in the NO2-arg+Cic
      group versus NO2-arg group (13.9 +/- 4.36 vs 63.4 +/- 21.6 mmHg; p < 0.01). IN
      CONCLUSION, chronic NO synthesis inhibition enhanced blood pressure and pressor
      responses to PGF2 alpha during pregnancy in rats. Chronic administration of
      cicletanine in Wistar pregnant rats decreases the response to vasopressor agents
      like PGF2 alpha. Moreover acute and chronic administration of cicletanine blunted
      the pressor effect, which was lower than in normal gestation.

PMID- 8572880
TI  - [Comparison of three methods for the estimation of spontaneous cardiac baroreflex
      sensitivity in normotensive and hypertensive subjects].
AB  - This study aimed at comparing estimations of spontaneous cardiac baroreflex
      sensitivity (BRS) obtained with 3 different methods from continuous non-invasive
      blood pressure recordings in humans. A new method, allowing the quantification of
      the statistical dependence between values of 2 parameters (Z coefficient), was
      applied to beat-to-beat systolic blood pressure (SBP) and heart period (HP)
      values. SBP and HP values with positive Z coefficient and corresponding to
      baroreflex activity (SBP and HP values both lower or higher than the modal
      values) were submitted to a linear regression and the regression coefficient
      (Zgain) was taken as an index of BRS. Second, cross-spectral analysis of SBP and
      HP gave a BRS value (Csgain) computed as the average value of transfer function
      moduli for frequencies between 0.07 and 0.14 Hz, with coherence between SBP and
      HP greater than 0.5. The third method relies on the analysis of linear sequences
      (r > 0.97) containing at least 3 values of SBP and HP varying in the same
      direction. The average regression coefficient obtained from all selected SBP and
      HP sequences is the index of BRS (Seqgain). SBP and HR were recorded during 1
      hour with a Finapres in 10 healthy male volunteers (NT), 23 to 32 year-old (SBP:
      123 +/- 2 mmHg) and 10 recent and untreated hypertensive subjects (HT) (SBP: 152
      +/- 6 mmHg). [table: see text] These results show that, in both groups, Zgain and
      Seqgain correlated with Csgain. No correlation was found between Zgain and
      Seqgain in healthy volunteers whereas the correlation was strong in hypertensives
      probably due to more heterogeneous SBP levels and BRS values in these subjects.
      This suggests that these methods are sensitive to different ways of response of
      the baroreflex.

PMID- 8572881
TI  - [Spectrum analysis of heart rate and arterial systolic pressure after heart
      transplantation in children].
AB  - The aim was to examine the short-term variability of blood pressure (BP) and
      heart rate (HR) in 19 children who had received heart transplants and in 8 normal
      control children. BP was determined by a finger arterial pressure device. We
      examined the power spectra for HR and systolic blood pressure (SBP) in the supine
      and standing posture. In the transplanted children we could distinguish two
      groups (groups A and B) in whom HR variability differed, though in both it was
      greatly reduced compared to controls (group C). In group A there were no
      significant fluctuations in the mid frequency (MF) range for HF. Gain of the
      relationship between SBP and HR was very low and there were virtually no HR
      changes associated with passive tilting. By contrast, in group B transplant
      patients the HR variability, as assessed by standard deviation was about half
      that of normal controls. The power spectra attenuation was greater in the high
      frequency (HF) than in the MF bands. On standing the latter became enhanced, but
      not the HF variability. The findings suggest some reinnervation involving cardiac
      sympathetic fibres to a greater degree than the fast-responding vagal fibres.
      Time since operation was a critical factor for reinnervation since all subjects
      from group B were transplanted more than 44 months prior to the recording. We
      conclude that in a proportion of children who have received heart transplantation
      there is a delayed reinnervation of the heart, which probably involves
      sympathetic effectors rather than the vagus.

PMID- 8572882
TI  - [Baroreflex sensitivity and vascular involvement in hypertension].
AB  - Relationships between baroreflex sensitivity (BRS) and arterial distensibility
      are evaluated by continuous measurement of blood pressure (Finapres) and carotid
      femoral pulse wave velocity measurement (PWV); 73 subjects are recruited on WHO
      criteria (age: 48 +/- 13). An ambulatory measurement of BP is also performed to
      evaluate the mean BP 24 level. The BRS is evaluated at rest during 20 min of
      acquisition data in a lying position, using a dedicated software [(automatic
      detection by of BP sequences were 3 or more systolic BP and RR interval increased
      of 1 mmHg for SBP and 4 ms for RR (PS+/RR+) or decreased (PS-/RR-)]. The BRS is
      the slope of the regression line between SBP and RR interval of each sequences
      (if correlation coefficient > 0.95). RESULTS: resting BP: SBP/DBP = 170 +/- 12
      mmHg. HR 72 +/- 15 batt/min, PWV = 10.8 +/- 3.2 m/s. Mean BRS is 8.2 +/- 3.8 for
      PS+/RR+ and 8.7 +/- 3.8 ms/mmHg PS-/RR-. The coefficient of correlation (Pearson)
      between PWV and BRS is -0.59* for PS+/RR+ and -0.41* for PS-/RR- (*: p < 0.01).
      In multivariate analyses, these relations were statistically independent of age
      and BP for the sequences PS+/RR+ but not for the sequences PS-/RR- suggesting a
      predominant vagal alteration in hypertensive subjects associated with the
      alteration of carotido-femoral pulse wave velocity.

PMID- 8572883
TI  - [Paul Milliez 1912-1994].

PMID- 8572885
TI  - Genetics of pentose-phosphate pathway enzymes of Escherichia coli K-12.
AB  - The pentose-phosphate pathway of Escherichia coli K-12, in addition to its role
      as a route for the breakdown of sugars such as glucose or pentoses, provides the
      cell with intermediates for the anabolism of amino acids, vitamins, nucleotides,
      and cell wall constituents. Through its oxidative branch, it is a major source of
      NADPH. The expression of the gene for NADP-dependent 6-phosphogluconate
      dehydrogenase (gnd) is regulated by the growth rate in E. coli. The recently
      identified gene for ribulose-5-phosphate 3-epimerase (rpe) is part of a large
      operon that comprises among other genes for the biosynthesis of aromatic amino
      acids. In recent years, genes for all enzymes of the pathway have been cloned and
      sequenced. Isoenzymes have been found for transketolase (genes tktA and tktB),
      ribose-5-phosphate isomerase (rpiA and rpiB) and transaldolase (talA and talB).

PMID- 8572886
TI  - Thermodesulforhabdus norvegicus gen. nov., sp. nov., a novel thermophilic sulfate
      reducing bacterium from oil field water.
AB  - A novel gram-negative, thermophilic, acetate-oxidizing, sulfate-reducing
      bacterium, strain A8444, isolated from hot North Sea oil field water, is
      described. The rod-shaped cells averaged 1 micron in width and 2.5 microns in
      length. They were motile by means of a single polar flagellum. Growth was
      observed between 44 and 74 degrees C, with an optimum at 60 degrees C. Spores
      were not produced. Sulfate and sulfite were used as electron acceptors. Sulfur,
      thiosulfate, nitrate, fumarate, and pyruvate were not reduced. In the presence of
      sulfate, growth was observed with acetate, lactate, pyruvate, butyrate,
      succinate, malate, fumarate, valerate, caproate, heptanoate, octanoate,
      nonadecanoate, decanoate, tridecanoate, pentadecanoate, palmitate,
      heptadecanoate, stearate, and ethanol. Pyruvate, lactate, and fumarate did not
      support fermentative growth. Cytochromes of the c-type were present.
      Desulfoviridin, desulforubidin, P582, and desulfofuscidin were not present. The
      G+C content of the DNA was 51 mol%. Sequence analysis of 16S rDNA showed that
      phylogenetically strain A8444 belongs to the delta subdivision of the
      Proteobacteria. The closest relatives are Desulfacinum infernum and
      Syntrophobacter wolinii: Strain A8444 is described as the type strain of the new
      taxon Thermodesulforhabdus norvegicus gen. nov., sp. nov.

PMID- 8572884
TI  - Genetics of gliding motility and development in Myxococcus xanthus.
AB  - Successful development in multicellular eukaryotes requires cell-cell
      communication and the coordinated spatial and temporal movements of cells. The
      complex array of networks required to bring eukaryotic development to fruition
      can be modeled by the development of the simpler prokaryote Myxococcus xanthus.
      As part of its life cycle, M. xanthus forms multicellular fruiting bodies
      containing differentiated cells. Analysis of the genes essential for M. xanthus
      development is possible because strains with mutations that block development can
      be maintained in the vegetative state. Development in M. xanthus is induced by
      starvation, and early events in development suggest that signaling stages have
      evolved to monitor the metabolic state of the developing cell. In the absence of
      these signals, which include amino acids, alpha-keto acids, and other
      intermediary metabolites, the ability of cells to differentiate into myxospores
      is impaired. Mutations that block genes controlling gliding motility disrupt the
      morphogenesis of fruiting bodies and sporogenesis in surprising ways. In this
      review, we present data that encourage future genetic and biochemical studies of
      the relationships between motility, cell-cell signaling, and development in M.
      xanthus.

PMID- 8572887
TI  - Metabolism of cyclohexane carboxylic acid by the photosynthetic bacterium
      Rhodopseudomonas palustris.
AB  - Cyclohexane carboxylate supported relatively rapid growth (doubling times 7-8 h)
      of Rhodopseudomonas palustris under oxic or photosynthetic conditions, but did
      not serve as a substrate for either of the known aromatic CoA ligases. A CoA
      ligase that thioesterifies cyclohexane carboxylate was partially purified and did
      not cross react immunologically with the two CoA ligases purified previously from
      this bacterium. Crude extracts of R. palustris cells grown with a range of
      aromatic or alicyclic acids contained a dehydrogenase that reacted with
      cyclohexane carboxyl-CoA or cyclohex-1-ene carboxyl-CoA, using 2,6
      dichlorophenolindophenol or ferricenium ion as electron carrier. This activity
      was not detected in extracts of adipate-, glutamate-, or succinate-grown cells.
      No oxidation or reduction of nonesterified cyclohexane carboxylate or cyclohexene
      carbocylate was detected in extracts of cells grown with aromatic or aliphatic
      substrates, neither aerobically nor anaerobically. A constitutively expressed
      thioesterase that hydrolyzed cyclohexane carboxyl-CoA and also some alicyclic and
      aliphatic CoA derivatives was purified and characterized. The enzyme had little
      or no activity on benzoyl-CoA or 4-hydroxybenzoyl-CoA. The presence of a
      thioesterase that effectively hydrolyzes cyclohexane carboxyl-CoA suggests that
      transient production of cyclohexane carboxylate is a physiological response to
      temporary excess of reductant during metabolism of aromatic compounds.

PMID- 8572888
TI  - Purification and characterization of dihydroorotase from Pseudomonas putida.
AB  - Dihydroorotase was purified to homogeneity from Pseudomonas putida. The relative
      molecular mass of the native enzyme was 82 kDa and the enzyme consisted of two
      identical subunits with a relative molecular mass of 41 kDa. The enzyme only
      hydrolyzed dihydro-L-orotate and its methyl ester, and the reactions were
      reversible. The apparent Km and Vmax values for dihydro-L-orotate hydrolysis (at
      pH 7.4) were 0.081 mM and 18 mumol min-1 mg-1, respectively; and those for N
      carbamoyl-DL-aspartate (at pH 6.0) were 2.2 mM and 68 mumol min-1 mg-1,
      respectively. The enzyme was inhibited by metal ion chelators and activated by
      Zn2+. However, excessive Zn2+ was inhibitory. The enzyme was inhibited by
      sulfhydryl reagents, and competitively inhibited by N-carbamoylamino acids such
      as N-carbamoylglycine, with a Ki value of 2.7 mM. The enzyme was also inhibited
      non-competitively by pyrimidine-metabolism intermediates such as dihydrouracil
      and orotate, with a Ki value of 3.4 and 0.75 mM, respectively, suggesting that
      the enzyme activity is regulated by pyrimidine-metabolism intermediates and that
      dihydroorotase plays a role in the control of pyrimidine biosynthesis.

PMID- 8572889
TI  - Different structure and expression of the operons encoding the membrane-bound
      hydrogenases from Methanosarcina mazei Go1.
AB  - The expression of the vho and vht operons from Methanosarcina mazei Go1, which
      each encode a membrane-bound hydrogenase and a cytochrome b, was analyzed under
      various growth conditions. Synthesis of both hydrogenases was induced at the
      level of transcription during methanogenesis from H2/CO2 or methanol. Transcripts
      of the vho operon were also detected when Ms. mazei Go1 was grown on acetate,
      indicating that this operon is constitutively expressed. In contrast, mRNA from
      the vht operon was not found in acetate-grown cells. Downstream of the structural
      genes vhtG and vhtA and the cytochrome-b-encoding gene vhtC, an additional open
      reading frame (vhtD; 486 bp) was identified. vhtD is followed by six tandem
      repeats of an 11-bp sequence, which is probably a termination site of
      transcription. Northern blots revealed that vhtD is part of the vht operon. In
      the vho operon, a vhtD-like gene and a terminator composed of tandem repeats
      could not be identified. The physiological function of two genetically distinct,
      membrane-bound hydrogenases from Ms. mazei Go1 is discussed.

PMID- 8572890
TI  - Is sex worth searching for?
AB  - Several methods of molecular sexing (i.e. detection of Y-chromosomal sequences)
      have been briefly presented. In addition to other applications they can be used
      for monitoring of patients after sex-mismatched bone marrow transplantation for
      mixed chimerism and for detection of fetal cells in maternal circulation.
      Clinical significance of mixed chimerism and possibilities of non-invasive
      prenatal diagnosis with the use of fetal cells isolated from peripheral blood of
      pregnant women has been described.

PMID- 8572891
TI  - Presentation of antigen by B cell subsets. II. The role of CD5 B cells in the
      presentation of antigen to antigen-specific T cells.
AB  - We demonstrate that peritoneal B cells have a much higher ability to present
      antigen to antigen-specific T cell lines than splenic B cells. Presentation of
      antigen by B cells is abrogated or drastically reduced after removal of Lyb-5+
      cells from the population of splenic or peritoneal B cells. Peritoneal B cells,
      precultured for 7 days prior to the antigen presentation assay, retain their
      antigen presenting cell (APC) function. Enrichment for CD5+ cells in the
      peritoneal B cell population results in a more effective antigen presentation.
      Lastly, stimulation of B cells via CD5 antigen, by treatment of cells with anti
      CD5 antibodies or cross-linking of CD5 receptors, enhances APC function of these
      cells. The results indicate, both indirectly and directly, that CD5+ B cells play
      a predominant role in the presentation of conventional antigens to antigen
      specific T cells.

PMID- 8572893
TI  - Presentation of antigen by B cell subsets. IV. Defective T-B cell signalling
      causes inability to present antigen by B cells from immunodeficient mice.
AB  - The purpose of this study was to investigate differences in T-B cell signalling
      between B cells from normal and immunodeficient mice. B cell blasts from normal
      and immunodeficient mice expressed comparable levels of membrane-associated IL-1.
      B cells from normal, but not immunodeficient mice, prefixed with glutaraldehyde
      and cultured with thymocytes or a T cell line BK33, induce in T cells production
      of a factor which causes release of IL-1 by macrophages. This factor,
      preincubated with B cells from immunodeficient mice significantly enhances their
      APC function. Furthermore, this cytokine induces expression of Lyb-5 alloantigen
      on B cells from immunodeficient mice. This effect could be blocked by
      neutralizing antibodies to IL-6 but not to IL-2, IL-4 or GM-CSF. We conclude that
      immature B cells from immunodeficient (CBA/N x BALB/c)F1 mice are unable to
      stimulate interacting T cells to produce IL-6 and therefore are inefficient
      antigen presenting cells.

PMID- 8572892
TI  - Presentation of antigen by B cell subsets. III. Effects of interleukins on
      antigen presenting function and phenotype of immature B cells.
AB  - In this report we demonstrate that B cells from CBA/N or (CBA/N x BALB/c)F1 male
      mice with x-linked immunodeficiency, that have very limited ability to present
      antigen to antigen-specific T cells, acquire this function following
      preincubation with IL-1, IL-4 and to a lesser degree with IL-6 and IL-5.
      Preincubation of normal B cells with these B-tropic interleukins does not lead to
      enhancement of their APC function. Incubation of B cells from the peritoneal
      cavity and spleen of xid mice with B cell tropic interleukins (IL-1, 4, 5 and 6),
      but not with IL-2 or IL-3, induces appearance of Lyb-5 antigen on these cells.
      The study demonstrates that the property of inducing APC activity in immature B
      cells is correlated with the acquirement of Lyb-5 antigen.

PMID- 8572894
TI  - Human immunoglobulin production in SCID mice following primary sensitisation of
      human lymphocytes in situ.
AB  - We have grafted human peripheral blood mononuclear cells to the peritoneal cavity
      of SCID mice, exposed them to soluble antigens in the absence of adjuvant and
      examined their ability to make specific antibody. The effect of in vitro pre
      priming of donor cells on antibody production was determined. Human IgM and IgG
      antibodies were found in the SCID serum following in situ antigenic challenge and
      there was good evidence of antigen specificity. The total Ig levels and the
      relative antigen binding ability were diminished by in vitro pre-priming. The
      results demonstrate that primary human antibodies against antigens to which the
      donor is probably naive can be generated by in situ sensitisation in SCID mice,
      but that optimisation for each antigen may be required.

PMID- 8572895
TI  - Development of IgG subclasses in healthy Polish children.
AB  - To determine the ontogeny of IgG subclasses in healthy Polish children IgG1,
      IgG2, IgG3, IgG4 concentrations were measured by enzyme-linked immunosorbent
      assay in 30 cord blood sera and sera from 152 healthy children aged 4 months to
      16 years. The geometric mean of concentrations all of IgG subclasses in age
      related groups of children were calculated. In cord sera, four IgG subclasses
      were found with the IgG1 level reaching about 90%, IgG2--52%, IgG3--80% and IgG4-
      33% of the mean adult values. In the group of youngest children (4-6 months of
      age) the concentration of all IgG subclasses were significantly decreased in
      comparison to initial values. Then, IgG1 and IgG3 levels increased rapidly
      reaching ca. 50% of the mean adult values by 1 year of age. We also demonstrated
      much slower maturation of IgG2 and IgG4 which lagged behind IgG1 and IgG3
      development, especially in younger children.

PMID- 8572896
TI  - Effect of hydrocortisone treatment on oxygen metabolism and phagocytosis of
      peripheral blood neutrophils in asthmatic patients, sensitive and resistant to
      glucocorticosteroid therapy.
AB  - The inflammatory activity of peripheral blood neutrophils of patients suffering
      from atopic asthma and treated with glucocorticosteroids was investigated. Two
      tests were performed: 1. chemiluminescence test of neutrophils, and 2.
      phagocytosis test of latex and bacteria (Staphylococcus aureus 209 P) by
      neutrophils before and after incubation of the cells with hydrocortisone. The
      tests were carried out in 3 selected groups of (1) asthmatic steroid sensitive
      patients, (2) asthmatic steroid resistant patients, and (3) healthy individuals.
      The neutrophil chemiluminescence stimulation index was found to be significantly
      lower in the asthmatic steroid sensitive group as compared to the other groups.
      The index increased in this group after neutrophil incubation with
      hydrocortisone. The results of phagocytosis of latex by neutrophils before and
      after their incubation with hydrocortisone were similar in all the 3 groups. The
      results of phagocytosis of bacteria by neutrophils in the asthmatic steroid
      sensitive group were significantly lower after incubation of neutrophils with
      hydrocortisone only.

PMID- 8572897
TI  - Essential edema-proteinuria-hypertension (EPH) gestosis and gestosis
      superimposing pre-existing renal disease: comparison of cellular immunity
      parameters.
AB  - The paper is aimed at evaluation of certain indices of cellular immunity in
      pregnant women with gestosis superimposing pre-existing renal diseases and
      comparing them with the immunological condition of women with essential gestosis.
      T lymphocyte subpopulations and lymphocyte proliferative responses to mitogens
      (phytohemagglutinin--PHA, concanavalin A--Con A and pokeweed mitogen--PWM) in the
      fetal calf serum and autological sera were studied. The groups of examined
      pregnant women in the 3rd trimester did not vary with regard to gestation age,
      calendar age and to the severity of edema (E), proteinuria (P) and hypertension
      (H) gestosis symptoms. It has been found that equal changes occur in both groups
      of women, regarding the examined indices of cellular immunity, when referred to
      normal pregnant women. In the gestotic women a decreased absolute and percentage
      content of CD8+ T cells and increased percentage of CD3+ and CD4+ lymphocytes
      were found in comparison with the normal pregnant women, which led to an almost
      2.5-fold increase of CD4+/CD8+ ratio. The sera of gestotic women, in comparison
      with the healthy pregnant group, strongly increased the proliferation of Con A
      and PWM-induced lymphocytes. It may then be assumed that the observed
      immunological changes do not coincide with the primary causes of gestosis. We
      suggest that immunological factors largely contribute to the development of
      essential gestosis and gestosis superimposing pre-existing renal disease.

PMID- 8572898
TI  - Polymorphonuclear leukocytes (PMN) activity in peripheral blood in patients with
      esophageal carcinoma.
AB  - The aim of this study was to evaluate some of the PMN functions connected with
      phagocytosis in 34 patients with esophageal carcinoma, confronted with a clinical
      progression of the neoplastic disease, according to TNM classification. The level
      of the neoplastic markers--SCC and CEA antigens were determined also. In the
      examined group of patients significant decrease in the mean values of FcR and CR
      receptors expression, migration, chemotaxis and phagocytosis of PMN were
      observed. No correlation was found between the percentage cells with FcR and CR
      and phagocytosis and clinical progression of neoplasma. Significant differences
      were in mean values of chemotaxis and migration in group with IV stage TNM. There
      was no found correlation between granulocytic tests and levels of SCC and CEA.

PMID- 8572899
TI  - Effect of blood transfusion and cyclophosphamide on cardiac allograft survival in
      sensitized mice.
AB  - In the H-2-incompatible donor-recipient model in mice (BALB/c-->CBA/H),
      combination of donor-specific blood transfusion (DST) on the day -9 before
      transplantation with both pre- and posttransplant immunosuppression with
      cyclophosphamide (CY) interacted beneficially to produce significant donor
      specific prolongation of cardiac graft survival. However, in recipients
      presensitized with donor-specific blood on the day -21, combination of DST with
      pre- and posttransplant CY immunosuppression did not act synergistically and
      graft survival in this group did not differ from that in presensitized mice
      treated with 2 doses of CY alone.

PMID- 8572900
TI  - Pharmacological properties of racemic chlorobromofosfamide.
AB  - Racemic chlorobromofosfamide (CBM-4A) is a bromine substituted analog of
      ifosfamide. The studies reported here were aimed at establishing the general
      pharmacological properties and toxicologic profile of this compound. Acute and
      cumulative toxicity, behavioral screening tests and effects of subchronic and
      chronic treatment (influence on body weight, mortality, blood morphology,
      proteins level, urea and creatinine concentration, enzymes activity) were taken
      into account. Summarized data revealed that CBM-4A possessed similar properties
      as other oxazaphosphorine cytostatics.

PMID- 8572901
TI  - Experimental antitumor activity and toxicity of the selected triazolo- and
      imidazoacridinones.
AB  - Toxicity and antitumor effects of four compounds from the groups of
      triazoloacridinones and imidazoacridinones were evaluated in transplantable tumor
      systems in mice, including P388 leukemia, B16 melanoma and 2 colon
      adenocarcinomas C26 and C38. Tested compounds had moderate antileukemic activity
      but were active against B16 melanoma and 3 of them were very efficacious against
      colon tumors, providing high percentages of "cures". Toxicity for healthy mice,
      as well as antitumor activity, were found to depend on a treatment protocol. The
      compounds were better tolerated and gave higher antitumor effects when given as
      fractionated treatment. They displayed also sex-dependent toxicity and activity.

PMID- 8572902
TI  - Seasonal modulation of interferon response in spotted sousliks (Spermophilus
      suslicus).
AB  - Interferon production in spotted sousliks in different physiological states: in
      summer activity, summer torpor, winter hibernation and awaked from winter
      hibernation was studied. Three different interferon inducers: poly rI:rC
      complexed with DEAE-dextran, lipopolysaccharide from E. coli (LPS) and tilorone
      hydrochloride were used. In comparison with sousliks active in summer, the
      interferon levels in serum and different organs of sousliks in winter hibernation
      after induction with tilorone hydrochloride, LPS and poly rI:rC were
      significantly lower. Decreased interferon response was also observed in sousliks
      in summer torpor and awaked from winter hibernation. In contrast to hibernation,
      artificial acidosis induced by placing sousliks in the atmosphere with a high
      concentration of CO2 enhanced interferon production.

PMID- 8572903
TI  - Treatment of chemotherapy-induced or idiopathic bone marrow aplasia with
      granulocyte colony-stimulating factor (G-CSF).
AB  - We report on our experience with the application of recombinant human granulocyte
      colony-stimulating factor (G-CSF, Neupogen, Hoffmann La Roche) in patients with
      various types of hematological malignancies, who had chemotherapy-induced
      myelosuppression, and in patients with idiopathic aplastic anemia. The
      administration of G-CSF was associated with marked increase in white blood cells
      counts (WBC) in twelve out of 14 treated patients. In one patient with aplastic
      anemia the WBC decreased rapidly to the initial value after the cessation of
      cytokine therapy. Significant increase of platelet number was observed in 6
      patients. No toxicity was encountered with the hematopoietic growth factor
      therapy. Our study points to the fact that G-CSF have a stimulating effect on the
      regeneration of hematopoiesis, particularly within the granulopoietic
      compartment. The effect can be obtained both in a case of idiopathic- and
      cytostatic-dependent marrow aplasia.

PMID- 8572904
TI  - Interferon and tumor necrosis factor responses of HIV+ patients as markers for
      monitoring of the AIDS progression.
AB  - The blood samples taken from 31 HIV+ and AIDS patients were used to study
      interferon (IFN) and tumor necrosis factor (TNF) responses. The IFN and TNF
      levels in plasma were determined. In the whole blood assay (whole blood diluted
      1:10 with culture medium) Newcastle disease virus (NDV) and phytohemagglutinin
      (PHA) were used as cytokine inducers. Blood leukocytes of HIV+ patients produced
      significantly less IFN-alpha after NDV stimulation than the cells of healthy (HIV
      ) individuals. On the other hand, the production of IFN-gamma in response to PHA
      was impaired only in AIDS patients with stage CDC IV and CD4+ cell number <
      200/microliters. These patients had also increased IFN levels in plasma.
      Particularly, the high level of IFN in plasma was frequently detected in patients
      with progressing AIDS with CD4+ cell number < 50/microliters. This type of IFN
      was identified as a mixture of acid-labile and acid-stable IFN-alpha. The IFN
      responses of HIV+ patients may be considered as markers for monitoring
      progression of AIDS and therapy.

PMID- 8572905
TI  - Attempts to isolation and characterization of autolymphocytotoxins from
      syphilitic sera.
AB  - To solve problem if autolymphocytotoxins (AL) present in syphilitic sera are not
      circulating immune complexes (CIC), sera containing strong AL activity and weak
      CIC were precipitated with polyethylene glycol (PEG). Received PEG-precipitates
      were filtrated on Bio-Gel A-1.5 column to separate CIC from AL. The Al were found
      in the first three after void volume fractions of the column. The fractions were
      examined on content of protein, sugar and sialic acid. The only correlation seen
      refers to the sugar and protein. The fraction which display the AL activity have
      the ratios of sugar to protein higher than non active fractions. The data
      indicated besides that AL is not CIC because it is not immunoglobulin nor
      Treponema pallidum antigen. For further biochemical characterization of these
      factors more material is needed.

PMID- 8572907
TI  - Synthesis and biological studies on analogs of cyclolinopeptide A with a
      shortened peptide chain.
AB  - Continuing our work on the immunosuppressive activity of cyclolinopeptide A
      (CLA), a cyclic nonapeptide of the sequence: c-(-Leu-Ile-Ile-Leu-Val-Pro-Pro-Phe
      Phe), we synthesized a series of 6 linear analogs of CLA, successively shortened
      at the N-terminus of the peptide chain. Immunosuppressive activity of acetates as
      well as trifluoroacetates of these peptides was investigated using PFC (humoral
      immunity) and DTH (cellular immunity) tests. It was found that the
      immunosuppressive potency of the peptides examined diminishes with shortening of
      the peptide chain. Octapeptide I with the sequence Ile-Ile-Leu-Val-Pro-Pro-Phe
      Phe was found to be the most active of the whole series. The immunosuppressive
      activity increased again for a tripeptide fragment of CLA of the sequence Pro-Phe
      Phe. The immunosuppressive activity of octapeptide probably depends on the
      suppression of IL-1, IL-6 and TNF production by the cells involved in immune and
      inflammatory response.

PMID- 8572906
TI  - Search for antibodies for immunoenzymatic assay of human lutropin.
AB  - Five peptides corresponding to human lutropin (hLH) subunit fragments were
      synthesized by a solid phase method and their physicochemical characteristics are
      presented. Antibodies induced in rabbits with 3 peptides of beta hLH fragments
      coupled to thyrotropin did not bind hLH and human chorionic gonadotropin (hCG).
      Also 2 synthetic peptides of alpha hLH fragments did not react with rabbit anti
      hLH, anti-hCG and anti-alpha hCG antibodies. Using 2 monoclonal anti-alpha hCG
      and anti-beta hLH antibodies a sensitive sandwich ELISA technique was elaborated.
      Using this technique stability of hLH was investigated. The ELISA was also
      applied for assays of urine hLH in normal and ovulation days.

PMID- 8572908
TI  - Cerebral laterality in homosexual males: preliminary communication using
      magnetoencephalography.
AB  - MEG-based auditory M100 source location in the left and right hemispheres of 8
      strictly homosexual and 9 strictly heterosexual males were compared to determine
      if this measure of interhemispheric laterality varies as a function of sexual
      orientation. MEG fields evoked by auditory tone pips were recorded from left and
      right hemispheres in response to contralateral ear stimulation. The source of the
      100-msec latency component, generated in the superior temporal gyrus, was
      estimated using a least squares inverse solution algorithm. Auditory sources in
      heterosexual men were significantly further anterior in the right hemisphere
      compared to the left hemisphere. Source locations in the homosexual men did not
      exhibit significant interhemispheric asymmetry, being similarly located in both
      hemispheres. Findings suggest an anatomic and/or functional difference in the
      superior temporal gyrus of at least some homosexual men.

PMID- 8572909
TI  - Gender differences in sexual desire: the effects of anger and anxiety.
AB  - The effects of anxiety and anger on subjective sexual desire in men and women,
      following Kaplan's model of hypoactive desire disorders, were examined. Gender
      appropriate erotic audiotapes containing statements designed to elicit anxiety,
      anger, or situationally appropriate feelings (control condition) were presented
      to 24 men and 24 women. Dependent measures included subjective anxiety and time
      to expressed desire to terminate the sexual encounter. Results indicated that,
      for women, both anger and anxiety significantly reduced desire relative to the
      control condition, with anger showing a more marked effect. For men, similar
      results were noted, although fewer differences were observed between the anxiety
      and anger conditions. Significantly more women (79%) than men (21%) indicated
      that they would have terminated the encounter during the anger condition. Results
      are discussed in light of potential gender differences in factors that influence
      sexual desire, with directions for future research highlighted.

PMID- 8572911
TI  - Southwest Asian and north African terms for homosexual roles.
AB  - Contrary to recent ethnocentric and contemporocentric claims that social
      categories for homosexual roles did not exist until late 19th-century northern
      European and North American medical discourse invented some, terms from a range
      of Islamic societies across a millennium are reviewed. Both age-stratified and
      gender-stratified sets of terms for male homosexual roles are discussed along
      with the problem of interpreting absence of evidence of lexemes for egalitarian
      homosexuality prior to the recent borrowing of "gay."

PMID- 8572910
TI  - Retrospectively measured individual differences in childhood sex-typed behavior
      among gay men: correspondence between self- and maternal reports.
AB  - Male sexual orientation is strongly associated with childhood sex-typed behavior,
      but there are also marked within-orientation differences. Gay men show increased
      variance compared to heterosexual men on retrospective measures of childhood sex
      typed behavior. Individual differences among gay men for their degree of sex
      typed behavior may have important implications. However, there has been little
      attention given to the reliability or validity of retrospective measures of such
      differences that are most common. Gay men and their mothers completed
      questionnaires assessing the men's sex-typicality during childhood. Results of
      structural modeling analyses found that mothers' and sons' reports were
      significantly associated, both regarding the general level of sex-typed behavior
      and the specific behaviors, supporting the validity of retrospectively measured
      individual differences for those characteristics.

PMID- 8572912
TI  - Sexual bondage: a review and unobtrusive investigation.
AB  - To investigate unobtrusively how individuals experience sexual bondage, we
      analyzed all messages about sexual bondage (N = 514) mailed to an international
      computerized discussion group on sexual bondage in 1990. The most frequent
      individual experience reported (n = 60) was playful use of bondage to explore new
      areas of sexual pleasure. Other frequent experiences were the exchange of power,
      intensified sexual pleasure, and tactile stimulation and bodily sensations.
      Preference for the dominant-initiator role was expressed in 71% of the messages
      by male heterosexuals, 11% of the messages by heterosexual females, and 12% of
      the messages by homosexual males. Preference for the submissive-recipient role
      was expressed in 29% of the messages by heterosexual males, 89% by heterosexual
      females, and 88% by homosexual males. In 33% of messages subjects stated that
      sexual bondage occurred simultaneously with sadomasochism or was perceived as
      part of it.

PMID- 8572913
TI  - Evidence for vaginal transmission of HIV.

PMID- 8572914
TI  - Investigations on the influence of Clenbuterol and recombinant porcine
      somatotropin on nitrogen and energy metabolism in growing pigs.
AB  - The effect of Clenbuterol and recombinant porcine Somatotropin (rpST) on the N
      and energy metabolism was tested by means of the respiration trial technique and
      compared with a control. In one experiment Clenbuterol was given per os on the
      nutrition level of three times energy maintenance requirement and in two
      experiments on the nutrition level 3.2 and 2.4 times energy maintenance
      requirement, rpST was injected s.c. The live weight gain of the treated animals
      was 9% (Clenbuterol), 18 and 24% (rpST) higher than that of the controls, protein
      energy deposition was 21% (Clenbuterol), 45 and 46% (rpST) higher and fat energy
      deposition was 14% (Clenbuterol), 33 and 37% (rpST) lower than that of the
      controls.

PMID- 8572915
TI  - [Energy and nitrogen metabolism of pregnant and lactating sows and suckling
      piglets. 3. Chemical composition and energy content of the animal body fractions
      as well as portions of the animal body fractions of empty body of nonpregnant,
      pregnant and lactating sows].
AB  - The study is based on the results obtained from the slaughter of 5 sows on the
      first day of pregnancy and the first day of the experiment respectively (pregnant
      and non-pregnant sows resp.), of 43 pregnant sows on the 56th, 84th, 98th, 105th
      and 113rd day of gestation as well as 17 lactating sows on the 26th day of
      lactation. The animal bodies of pregnant sows were divided in 15 fractions and
      those of non-pregnant and lactating sows in 12 fractions. The investigations were
      carried out with 3 x 3 variants of litter number (1, 2, 4) and energy supply
      (120, 100, 80% of requirement recommendation). The chemical composition and the
      energy content of the animal body fractions as well as their relative portions of
      the empty body were largely constant during the course of gestation with the
      exception of the reproductive organs and the conception products. The
      physiological stage of lactation connected with limited mobilization of body
      reserves resulted in a reduction in fat content of some body fractions as well as
      a limited increase of the portions of body organs contrary to the portions of
      body tissues of the empty body. In comparison with sows of litter numbers 1 and 2
      the sows of litter number 4 were characterized by higher portions of bones and
      meat, valuable parts as well as by smaller portions of depotfat and meat from
      head and belly of empty body. The raising of the energy supply of the pregnant
      sows increased the portion of the depotfat and decreased the portion of the meat,
      valuable parts of the empty body. The chemical composition of the reproductive
      organs and the conception products as well as the portions of these fractions of
      the empty body were influenced strongly from the course of the gestation and
      lactation resp. The portions of the reproductive organs and of the conception
      products are small (related to energy < or = 5.7 and < or = 2.6% resp.)

PMID- 8572916
TI  - [Hydrocarbon content in the fat of meat pigs after feeding "Fermosin"].
AB  - In 5 different pig feeding experiments with 281 pigs the effect of the SCP
      "Fermosin" (n-alcane grown yeast) on the content of hydrocarbons (HC) in pig fat
      was studied. The control groups got SCP free feed and the experimental groups
      different quantities of "Fermosin". At 65-75 kg and 115 kg live weight pigs were
      slaughtered, and fat was taken for the HC determination. With increasing
      "Fermosin" content in the rations the HC and aromate content in the fat increased
      significantly. When the experimental groups got the control ration (SCP free) in
      the 2. fattening period, the content of HC and aromates decreased to the values
      of the control animals. The HC elimination took place at a rate of 1-2% per day.
      For the deposition of HC from the n-alcane grown yeast into the pigs' fat the
      regression equation y = 0.015 x was calculated (y = g HC in animal fat; x = g
      absorbed HC from SCP in the feed ration). The apparent absorption of HC was on an
      average 60% (range from 50 to 80%).

PMID- 8572917
TI  - Influence of Avotan on the microflora and concentrations of ammonia and volatile
      fatty acids in the rumen.
AB  - The influence of Avotan (Firm Cyanamid) was studied on VFA concentration, pH,
      dynamics of NH3 and on numbers of chosen species of rumen microorganisms in
      physiological experiments with four young bulls and two wethers with rumen
      cannulas. It was found no marked physiological change in pH of rumen fluid under
      the influence of Avotan. Difference between groups were statistical significant.
      Avotan caused significant (P < or = 0.01) decrease of molar % of acetic acid
      (from 67.0 to 62.1) and an increase of propionic acid (from 16.41 to 28.21 mol %)
      in wethers. These changes were nonsignificant with bulls. The acetate: propionate
      ratio decreased significantly from 4.1 to 2.2 in wethers. Avotan decreased highly
      significantly (P < or = 0.01) the level of NH3 in the rumen fluid during the
      observed period (0, 1.5, 3, 4.5 and 6 hours after feeding) in bulls. It was
      observed the similar effect in wethers 3 hours after feeding (from 170 mmol to 81
      mmol/l). Decrease of the total number of microorganisms in the rumen fluid was
      observed in animals which received Avotan (on the average 3.5 times in young
      bulls, and 4.5 times in wethers). The number of enterococci decreased
      significantly (2.8-4.5 times), number of amylolytic bacteria decreased less
      significantly.

PMID- 8572918
TI  - [Effect of feeding protected arginine on food intake, milk yield and growth
      hormone and amino acid levels in blood plasma of cows during the summer feeding
      period with grass].
AB  - The influence of a daily additon of 130 g arginine and 30 g lysine in a ruminally
      protected form on the content of growth hormone, amino acids and urea in blood
      plasma, milk yield and components and also feed intake under summer feeding
      conditions in an experimental period of eight weeks was investigated. The forage
      intake from grass was ad libitum. After a preperiod a total of 24 dairy cows were
      divided into 12 blocks, two cows in each, to consider milk yield, days postpartum
      and number of calving. The concentrate level of the treated group acted according
      to the control animals in each block. The growth hormone contents and the
      concentrations of arginine and lysine in blood plasma were not influenced by the
      addition of protected arginine. Urea content in blood plasma was increased in the
      treated cows tendentious in week 2 and significantly in the weeks 5 and 8. The
      decrease in milk yield in comparison with the preperiod was diminished in the
      arginine group by an average of 0.9 kg/d compared with the control, in the case
      of milk fat content it was significantly lowered. The milk protein and lactose
      contents were not changed by the treatment. The average daily forage intake was
      unchanged in the arginine group.

PMID- 8572919
TI  - The energy value for and nutritive value of para-rubber seed for rats.
AB  - The digestible (DE) and metabolizable energy (ME) of full-fat and defatted rubber
      seed meals (FRS and DRS) were determined with weanling albino rats fed diets in
      which the meals replaced either 20 or 40% glucose monohydrate in the reference
      diet. The nutritive value of both FRS and DRS included at 10, 20 and 30% of the
      diet as substitutes for groundnut meal and yellow maize was studied with 56, 28
      day-old albino rats of the Wistar strain. The trial lasted 28 days. Nutrient
      digestion and nitrogen retention were studied at the end of the second week on
      test. The DE and ME for FRS were on average 24.7 +/- 1.30 and 21.7 +/- 0.80 hy/g
      dry matter and those for DRS were 15.3 +/- 0.97 and 13.8 +/- 0.46 hy/g dry
      matter. Incorporation of rubber seed meals at increasing levels in the diet
      significantly depressed gains and worsened feed/gain ratio (P < 0.01), the diet
      containing 30% FRS or 20 and 30% DRS being significantly inferior to the control
      and the diet with 10% FRS or DRS. Significantly (P < 0.01) superior gains but not
      feed intake and efficiency were obtained for FRS compared to DRS. Percent intake 
      N retained also decreased with increasing rubber seed levels in the diet. Except
      for the significantly (P < 0.05) higher crude fibre digestibility of the control
      diet compared with those containing 20 or 30% FRS or DRS, the digestibilities of
      other nutrients were not significantly different.

PMID- 8572920
TI  - [Toasted rapeseed meal in broiler fattening diet].
AB  - A fattening trial of six week duration using male broiler chicks of the TETRA 82
      genotype has been performed to evaluate the feeding value of rapeseed meal
      derived from the following rapeseed origins of so-called double-zero quality:
      Canola (Cananda), Jantar (Poland) and the new-bred East German-genotype BNW 1.43,
      each at a diet level of 12%. Moreover, the indigenous origin has been
      investigated at levels of 6 and 18% in practical broiler rations as a protein
      source instead of soybean meal (partial replacement). The fattening results (live
      weight development, intake and conversion of feed, mortality) do not show
      disadvantageous effects by the different rapeseed meal origins, and the various
      levels too. The chemical whole-body composition gives reduced fat and more
      protein in broiler's carcass at a diet level of 12 and 18% of BNW 1.43-rapeseed
      meal. Blood plasma levels of T3 and T4 have refered to beginning status of
      hypothyreodism, higher percentages of rapeseed mean had been fed. Weight of
      broiler's thyroid varied independtly of treatment. Also by the means of
      histometrical investigation of these glands the effects known for conventional
      rapeseed meals could be demonstrated, however in an important weakly extent. In
      comparison to discrepancies in the literature results regarding the possible
      inclusion of double-zero rapeseed meal in broiler diets, it seems a maximum diet
      level of 12% of toasted rapeseed meal of used qualities could be recommended for
      practical diet formulation (without of performance depressions). However, further
      investigations are be essential in these questions.

PMID- 8572921
TI  - Feeding value of whole-crop wheat silage for ruminants related to stage of
      maturity and cutting height.
AB  - Wheat was harvested five times during maturation, ranging from the middle of the
      milk stage to the transition to yellow ripeness (YR, cutting height of 10 to 12
      cm), and ensiled. At the last two stages of maturity, the plants also were cut at
      34 to 36 cm. The effect of stage of maturity on digestibility of dietary OM by
      sheep fed at maintenance was modest, but significant (linear effect, P < 0.01,
      silage mean 69.4%). Voluntary intake of OM was affected differently by increasing
      stage of maturity: it first declined but then rose as wheat reached the YR stage
      (quadratic effect; P < 0.10, silage YR + 28 g/kg body weight). The energetic
      feeding potential, calculated as the voluntary intake of digestible OM, was not
      affected by stage of maturity or by cutting height (P > 0.1). When the proportion
      of stem decreased, OM digestibility increased by 2 to 3 percentage units, but
      voluntary intake was not changed (P > 0.1). Digestibility of crude fibre
      decreased, and digestibility of NDF and ADF tended to decrease with increasing
      stage of maturity (68 to 63%, 62 to 59% and 58 to 55% respectively), whereas the
      cell wall fractions analysed at the level of single sugars showed no distinct
      changes. In contrast, decreasing the proportion of stem increased the
      digestibility of all cell wall fractions except galactose and arabinose. Based on
      available information about the conservation problems associated with later
      stages of maturity, wheat should be harvested for whole-crop silage at the
      beginning of the dough stage with a normal, low cutting height.

PMID- 8572922
TI  - The international validation study of the acute toxic class method (oral).
AB  - An alternative to the oral LD50 test, the acute toxic class (ATC) method (oral),
      was validated with 20 substances in an international collaborative study with
      nine laboratories in five countries. The ATC method is a stepwise procedure with
      the use of three animals per step. It has been designed with three fixed doses
      (25, 200 and 2000 mg/kg). In general, this testing is sufficient for allocation
      to the toxicity classes of the majority of the international classification
      systems currently in use. The selection of testing at additional fixed doses (5,
      50 and 500 mg/kg) may be considered if further refinement is necessary or for
      specific allocation to those international classification systems with a cut-off
      value of 5 mg/kg. On average, two to four steps are necessary to complete a test.
      With the ATC method substances can be ranked in a similar or even better manner
      than with an LD50 test but it uses up to 90% fewer animals, the average being 70%
      fewer. This also results in substantially fewer moribund/dead animals. The ATC
      method is based on biometric evaluations that, together with the experimental
      results, demonstrate that this method is a sensitive and reliable alternative to
      the LD50 test.

PMID- 8572923
TI  - An approach for evaluating the respiratory irritation of mixtures: application to
      metalworking fluids.
AB  - Recently, the sensory and pulmonary irritating properties of ten metalworking
      fluids (MWF) were assessed using a mouse bioassay. Relative potency of the MWFs
      was estimated, but it was not possible to identify the component(s) responsible
      for the the respiratory irritation induced by each MWF. One of the ten fluids,
      MWF "ET", produced sensory and pulmonary irritation in mice, and it was of
      moderate potency in comparison to the other nine MWFs. MWF "E" had three major
      components: tall oil fatty acids (TOFA), sodium sulfonate (SA), and paraffinic
      oil (PO). In the present study, the sensory and pulmonary irritating properties
      of these individual components of MWF "E" were evaluated. Mixtures of the three
      components were also prepared and similarly evaluated. This analysis revealed
      that the sensory irritation from MWF "E" was largely due to TOFA, whereas SA
      produced the pulmonary irritation observed with MWF "E". Both TOFA and SA were
      more potent irritants than was MWF "E", and the potency of TOFA and/or SA was
      diminished through combination with PO. There was no evidence of synergism of the
      components when combined to form MWF "E". This approach for identifying the
      biologically "active" component(s) in a mixture should be useful for other MWFs.
      Furthermore, the approach should be easily adapted for other applications
      involving concerns with mixtures.

PMID- 8572924
TI  - Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on tryptophan and glucose
      homeostasis in the most TCDD-susceptible and the most TCDD-resistant species,
      guinea pigs and hamsters.
AB  - We have previously reported that in rats 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) lethality is associated (although not necessarily causally) with changes
      in brain serotonin (5-HT) metabolism. In the present study, we have examined
      whether this holds for other species by comparing the effect of TCDD in the most
      TCDD-susceptible and the most TCDD-resistant species, guinea pigs and hamsters,
      respectively. Body weight gain of guinea pigs exposed to TCDD (0.3-2.7
      micrograms/kg) diminished dose dependently, while the effect was marginal in
      hamsters (900-4600 micrograms/kg). Brain 5-hydroxyindoleacetic acid (the main
      metabolite of brain 5-HT), brain tryptophan (the precursor amino acid of 5-HT),
      and plasma free and total tryptophan were not affected at any dose in guinea
      pigs. In contrast, 4 days after exposure, the levels of plasma free and total
      tryptophan were consistently increased in hamsters. These, as well as brain
      tryptophan, were still elevated 10 days after exposure. TCDD did not affect
      plasma glucose level in either species. Liver glycogen was decreased in a dose
      dependent manner in TCDD-treated guinea pigs as well as in their pair-fed
      controls on day 10. There was no change in liver glycogen in hamsters. The
      activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase was only
      depressed in hamsters by all doses of TCDD. We conclude that changes in
      tryptophan metabolism or in carbohydrate homeostasis cannot explain the wide
      interspecies differences in susceptibility to the acute lethality of TCDD,
      although they may correlate with some aspects of its toxicity in certain species.

PMID- 8572925
TI  - Aspirin-like drugs can protect human T lymphocytes against benzoquinone
      cytotoxicity: evidence for a NAD(P)H:quinone reductase-dependent mechanism.
AB  - Benzene toxicity towards lymphocytes is thought to be mediated by metabolites of
      benzene including benzoquinone (BQ). NAD(P)H:quinone reductase (QR) is known to
      protect against BQ toxicity. The expression of the QR gene is regulated by the
      transcription factor AP-1. We had previously found that aspirin-like drugs (ALD)
      induce AP-1 in human T lymphocytes. It was therefore hypothesized that ALD would
      protect lymphocytes against BQ toxicity by inducing QR. Molt-4 cells (M4), a
      human T lymphocyte cell line, were incubated with different concentrations of two
      ALD, flurbiprofen and sodium diclofenac, and then exposed to BQ. Toxicity was
      measured by viability (trypan blue exclusion). Both drugs protected the cells
      against BQ cytotoxicity in a dose-dependent manner, e.g., sodium diclofenac at 15
      microM reduced the fraction of BQ-treated dead cells by 70%. ALDs induced QR
      activity in the M4 cells in the same range of concentrations that protected the
      cells against BQ toxicity. The protective effect of ALD was significantly reduced
      by dicoumarol, a QR-specific inhibitor. Since human T cells and T cell lines do
      not metabolize arachidonic acid, our data suggest that ALD can protect human T
      lymphocytes against a metabolite of benzene by induction of QR activity.

PMID- 8572926
TI  - Comparative effects of two dithiocarbamates disulfiram and thiram, on adrenal
      catecholamine content and on plasma dopamine-beta-hydroxylase activity.
AB  - Both disulfiram (tetraethylthiuram disulfide), an alcohol aversive drug, and
      thiram (tetramethyl-thiuram disulfide), a widely used pesticide, significantly
      increased the dopamine pool in the adrenal glands of dosed rats. The dopamine
      increase was detectable within 4 h of oral dosing with 100 mg/kg of either
      dithiocarbamate and peaked 24 h later at 10 times control values. In control rats
      the dopamine turnover was 0.51 h-1 as calculated by the assumed first order
      decline of dopamine after a single injection of alpha-methyl-p-tyrosine (alpha
      MT, 400 mg/kg i.p.) resulting in a dopamine-beta-hydroxylase (DBH) activity of
      0.73 nmol/h per pair of adrenals. In the adrenals of rats pretreated with thiram
      and then injected with alpha-MT, the adrenal dopamine content did not
      significantly decline, indicating that thiram reduced the conversion of dopamine
      to noradrenaline, eventually leading to the observed dopamine increase. Plasma
      DBH activity was significantly reduced 4 h and 24 h after dosing with thiram, but
      was unchanged after treatment with disulfiram. The determination of plasma DBH
      activity could be a marker to monitor the effect of thiram on catecholamine
      metabolism in occupationally exposed workers but not that of disulfiram in
      abstinent alcoholics.

PMID- 8572927
TI  - Effect of methyl isocyanate on rabbit cardiac Na+, K(+)-ATPase.
AB  - The present study describes the effect of methyl isocyanate (MIC) on rabbit
      cardiac microsomal Na+, K(+)-ATPase. Addition of MIC in vitro resulted in dose
      dependent inhibition of Na+, K(+)-ATPase, Mg(2+)-ATPase and K(+)-activated p
      nitrophenyl phosphatase (K(+)-PNPPase). Activation of Na+, K(+)-ATPase by ATP in
      the presence of MIC showed a decrease in Vmax with no change in Km. Similarly,
      activation of K+ PNPPase by PNPP in the presence of MIC showed a decrease in Vmax
      with no change in Km. The circular dichroism spectral studies revealed that MIC
      interaction with Na+, K(+)-ATPase led to a conformation of the protein wherein
      the substrates Na+ and K+ were no longer able to bind at the Na(+)- and K(+)
      activation sites. The data suggest that the inhibition of Na+, K(+)-ATPase was
      non-competitive and occurred by interference with the dephosphorylation of the
      enzyme-phosphoryl complex.

PMID- 8572928
TI  - Characterization of the arteritis induced by infusion of rats with UK-61,260, an
      inodilator, for 24 h. A comparison with the arteritis induced by fenoldopam
      mesylate.
AB  - Administration of fenoldopam mesylate (FM), a dopaminergic agonist, or of cyclic
      cAMP phosphodiesterase inhibitors (PDE III), for example theophylline and
      caffeine, induces arteritis in the rat. In this study we characterized the
      arteritis induced by UK-61,260, an investigational inotropic agent with
      vasodilatory properties which displays an inhibitory action on cyclic AMP
      phosphodiesterase, in comparison with lesions induced by FM. The compounds were
      administered to Sprague-Dawley rats by intravenous infusion over 24 h (FM and UK
      61,260), orally or subcutaneously (UK-61,260); the rats were killed and
      necropsied for pathological examination at various times between 0 h and 28 days
      post-infusion. Infusion of UK-61,260 at doses of 100, 300 or 400 mg/kg produced
      arteritis mainly in the mesenteric arteries and occasionally in the renal,
      pancreatic, gastric and coronary arteries. There were no arterial lesions after
      infusion of 30 mg/kg, or after administration of 30, 100 or 200 mg/kg per day
      subcutaneously for 7 days, or after acute administration of 100, 300, 400 or 600
      mg/kg orally. Infusion of rats with 72 or 144 mg/kg FM produced arteritis over a
      wider range of tissues than did UK-61,260. However, the arterial lesions produced
      by infusion of either drug have the same initial aspect and a similar evolution
      with time. Immediately after the end of the infusion, minimal necrosis and
      haemorrhage occurred in the media only, without involvement of the endothelium or
      the perivascular space. This indicates that the media of the artery is the
      primary site of injury. The lesions seen 1 and 3 days post-infusion were
      characterized by severe medial necrosis and haemorrhage with perivascular acute
      inflammation and appeared macroscopically as haemorrhagic spots on the vessels.
      On days 7, 14 and 28 post-infusion, no medial necrosis or haemorrhage were
      present, while perivascular chronic inflammation and moderate smooth muscle
      hyperplasia were seen. It appeared, therefore, that the lesions underwent repair
      in 28 days, but footprints of the damage were still present 28 days post
      infusion. The similarity between arteritis induced in rats by fenoldopam or by UK
      61,260, at doses inducing PDE III inhibition, is consistent with the view that
      they have a similar pathogenesis. In our view it is probable that these
      pharmacologically and chemically distinct drugs trigger an increase in
      intracellular levels of cAMP which in turn triggers vascular damage. The arterial
      changes observed in the current study after acute administration may explain the
      increased incidence of polyarteritis nodosa occurring in long term toxicity
      studies with FM or PDE III inhibitors.

PMID- 8572929
TI  - Triphenylphosphite neuropathy in hens.
AB  - Single doses of triphenyl phosphite (TPP), a triester of trivalent phosphorus,
      cause ataxia and paralysis in hens. Characteristics of neurotoxicity were
      described as somewhat different from organophosphate induced delayed
      polyneuropathy (OPIDP), which is caused by triesters of pentavalent phosphorus.
      The onset of TPP neuropathy was reported to occur earlier than that of OPIDP (5
      10 versus 7-14 days after dosing, respectively), and chromatolysis, neuronal
      necrosis and lesions in certain areas of the brain were found in TPP neuropathy
      only. Pretreatment with phenylmethanesulfonyl fluoride (PMSF) protects from
      OPIDP, but it either partially protected from effects of low doses or exacerbated
      those of higher doses of TPP. In order to account for these differences with
      OPIDP, it was suggested that TPP neuropathy results from the combination of two
      independent mechanisms of toxicity: typical OPIDP due to inhibition of neuropathy
      target esterase (NTE) plus a second neurotoxicity related with other target(s).
      We explored TPP neuropathy in the hen with attention to the phenomena of
      promotion and protection which are both caused by PMSF when given in combination
      with typical neuropathic OPs. When PMSF is given before neuropathic OPs it
      protects from OPIDP; when given afterwards it exaggerates OPIDP. The former
      effect is due to interactions with NTE, the latter to interactions with an
      unknown site. The time course of NTE reappearance after TPP (60 or 90 mg/kg i.v.)
      inhibition showed a longer half-life when compared to that after PMSF (30 mg/kg
      s.c.) (10-15 versus 4-6 days, respectively). The clinical signs of TPP neuropathy
      (60 or 90 mg/kg i.v.) were similar to those observed in OPIDP, appeared 7-12 days
      after treatment, correlated with more than 70% NTE inhibition/aging and were
      preceded by a reduction of retrograde axonal transport in sciatic nerve of hens.
      TPP (60 mg/kg i.v.) neuropathy was promoted by PMSF (120 mg/kg s.c.) given up to
      12 days afterwards and was partially protected by PMSF (10-120 mg/kg s.c.) when
      given 24 h before TPP (60 or 90 mg/kg i.v.). The previously reported early onset
      of TPP neuropathy might be related to the higher dose used in those experiments
      and to the resulting more severe neuropathy. The lack of full protection might be
      explained by the slow kinetics of TPP, which would cause substantial NTE
      inhibition when PMSF effects on NTE had subsided. Since PMSF also affects the
      promotion site when given before initiation of neuropathy, the resulting
      neuropathy would then be due to both protection from and promotion of TPP effects
      by PMSF. No promotion by PMSF (120 mg/kg s.c.) was observed in TPP neuropathy (90
      mg/kg i.v.) partially protected by PMSF (10-30 mg/kg s.c.). This might also be
      explained by the concurrent effects on NTE and on the promotion site obtained
      with PMSF pretreatment. We conclude that TPP neuropathy in the hen is likely to
      be the same as typical OPIDP. The unusual effects of combined treatment to hens
      with TPP and PMSF are explained by the prolonged pharmacokinetics of TPP and by
      the dual effect of PMSF i.e. protection from and promotion of OPIDP.

PMID- 8572931
TI  - Effect of lead on tube formation by cultured human vascular endothelial cells.
AB  - The effect of lead acetate (Pb) on the growth of and tube formation by cultured
      human umbilical vascular endothelial cells (HUVEC) was examined. HUVEC were
      collected by enzymatic digestion with collagenase. The number of viable cells of
      HUVEC was negligibly affected by cultivation with Pb at concentrations of 1-100
      microM, but was slightly reduced by cultivation at 500 microM. Tube formation was
      studied by culturing the cells on a gelled basement membrane matrix (Matrigel).
      Treatment of HUVEC with 0.1-50.0 microM Pb for 24 h inhibited tube formation dose
      dependently. The length of tube formation decreased time-dependently with 1.0
      microM Pb. These findings suggest that Pb inhibits the formation of a capillary
      network by HUVEC, and that Pb could be injurious to endothelial cell function.

PMID- 8572930
TI  - Effect of DMPS and various adsorbents on the arsenic excretion in guinea-pigs
      after injection with As2O3.
AB  - The present experiments were performed to test the possibility of interrupting
      the enterohepatic circulation of arsenic (As). Therefore the efficacy of
      adsorbents to bind As and/or As-DMPS adducts in vitro and their effect on the
      excretion of As into the feces and urine in vivo were investigated after
      injection of As2O3 and DMPS in guinea-pigs. The adsorbents bentonite, activated
      charcoal or colestyramine, respectively, were tested. Only slight binding of 73As
      (< 5% of the 73As dose) was observed to all adsorbents in vitro. After addition
      of DMPS, a good binding was found for 73As to colestyramine (50%) or activated
      charcoal (60%), respectively. However, the 73As-DMPS adduct was removed from the
      activated charcoal during washing. In the first in vivo experiment, male guinea
      pigs (n = 4/group) received As2O3 [0.02 mmol As(III)/kg s.c. labelled with a
      tracer dose of 73As(III) (0.14 kBq/g)], 30 min later DMPS (0.1 mmol/kg i.p.) and
      by gastric tube (10 ml/kg body wt) either saline, bentonite (1 g/kg), activated
      charcoal (1 g/kg) or colestyramine (0.2 g/kg), respectively. Urine and feces were
      collected for 24 h. No increase in 73As excretion into the feces was observed
      after administration of DMPS and all adsorbents, compared to control animals. In
      the second in vivo experiment male guinea-pigs (n = 4/group) received the same
      As2O3 (+ 73As)- and DMPS dose. In addition, with a gastric tube (10 ml/kg)
      saline, colestyramine (0.2 g/kg), DMPS (0.1 mmol/kg), or the combination of DMPS
      (0.1 mmol/kg) + colestyramine (0.2 g/kg) were administered according to the
      scheme given in the following table. The amount of feces excreted did not differ
      between groups. Excretion of 73As within the feces during the first 12 h after As
      injection is shown in the following table (mean +/- SEM). The same amount of 73As
      (34% of the 73As dose) was excreted into the urine from animals in groups 4 and 5
      during this time. Obviously, the combined oral administration of DMPS +
      colestyramine markedly enhanced fecal excretion of As mobilized by DMPS i.p. It
      is suggested that interruption of enterohepatic circulation of As may be a
      valuable adjunct in the treatment of As poisoning.

PMID- 8572932
TI  - Inhibition of gamma-glutamyltranspeptidase decreases renal deposition of mercury
      after mercury vapor exposure.
AB  - The alteration of renal deposition of mercury (Hg) after mercury vapor (Hg0)
      exposure was studied in mice pretreated with acivicin, a potent and irreversible
      inhibitor of gamma-glutamyltranspeptidase (GGT). Pretreatment with acivicin
      decreased renal Hg concentration by about 60% and significantly increased Hg
      concentration in the urine compared with the non-treated group. The results
      suggest that renal deposition of Hg after Hg0 exposure depends on renal GGT,
      which plays an important role in the uptake of GSH or GSH conjugates filtered
      through the glomeruli. It seems that the mechanism of renal Hg deposition after
      Hg0 exposure is similar to that after exposure to ionic Hg: a GGT-mediated
      incorporation of an Hg-GSH complex into renal tubular cells. The acivicin
      pretreatment after Hg0 exposure did not affect Hg concentrations in the liver and
      erythrocytes.

PMID- 8572933
TI  - Hydrolysis rates of pyrrolizidine alkaloids derived from Senecio jacobaea.
AB  - Many of the commonly studied pyrrolizidine alkaloids (PAs) are built upon the
      subgroup retronecine (RET), which is released from the parent molecule by either
      base catalyzed or enzymatic hydrolysis of the ester linkages. The rate of
      appearance of RET in a hydrolytic study would thus reflect the rate of hydrolysis
      for the PA being tested. We have developed a gas chromatographic (GC) method to
      measure the release of RET from incubations of PAs with the guinea pig
      carboxylesterase, GPH1. The PAs tested were the following: jacobine (JAB),
      jacozine (JAZ), retrorsine (RES), and seneciphylline (SNP). The KmS for SNP and
      JAZ were determined to be 64.9 and 349.2 microM, respectively. In addition, a
      qualitative assessment of hydrolytic activity toward a radiolabelled mixture of
      retrorsine/riddelliine (RES/RIL) was performed with HPLC and radiometric
      detection.

PMID- 8572934
TI  - The biometrical evaluation of the OECD modified version of the acute toxic class
      method (oral)

PMID- 8572935
TI  - Ultrastructural characteristics of Sin Nombre virus, causative agent of
      hantavirus pulmonary syndrome.
AB  - A previously unrecognized disease, hantavirus pulmonary syndrome, was described
      following an outbreak of severe, often lethal, pulmonary illness in the
      southwestern United States in May-June, 1993. We have now studied the morphologic
      features of the causative agent, Sin Nomber virus (SNV), by thin section electron
      microscopy and immunoelectron microscopy of infected Vero E6 cells. SNV virions
      were roughly spherical and had a mean diameter of 112 nm. They had a rather dense
      envelope and closely apposed fine surface projections, 7 nm in length.
      Filamentous nucleocapsids were present within virions. Viral inclusion bodies
      were present in the cytoplasm of infected cells; these appeared granular or
      filamentous, depending on the plane of section. All of these characteristics were
      similar to published descriptions of other hantaviruses; however, unlike all
      other hantaviruses and virtually all other member viruses of the family
      Bunyaviridae which bud upon smooth intracytoplasmic membranes, SNV budding
      occurred almost entirely upon the plasma membrane of infected cells. Virus
      budding was associated with the formation of long 28 nm diameter tubular
      projections. Occasional elongated 47 nm diameter virus-like particles were seen
      to bud upon intracytoplasmic membranes. As shown by immunoelectron microscopy,
      viral antigens were localized over virions, inclusions, and tubular projections
      associated with virion morphogenesis.

PMID- 8572936
TI  - Host dependent variation of hepatitis C virus: phylogenetic analyses.
AB  - Hepatitis C virus quasispecies in six patients from three families were separated
      by single strand conformation polymorphism analysis and by determination of
      nucleotide sequences of envelope regions containing the E1 gene segment and
      hypervariable region-1 of each quasispecies. Four of the six patients had
      multiple quasispecies. Phylogenetic analyses indicated that all quasispecies from
      one individual were highly homologous to each other. The homology was higher in
      the E1 gene segment than in hypervariable region-1. Furthermore, all quasispecies
      found in members of one family (husband and wife) were also highly homologous,
      suggesting direct intrafamilial transmission. The direction of hepatitis C virus
      variation in hypervariable region-1, however, seems to differ depending on the
      host in intrafamilial transmission.

PMID- 8572938
TI  - Studies on the single-shelled rotavirus receptor with a synthetic peptide derived
      from the cytoplasmic domain of NS28.
AB  - The nonstructural glycoprotein NS28 of rotaviruses plays an important part in the
      assembly of double-shelled rotaviruses. C-terminal domains of the protein
      function as a receptor for single-shelled rotavirus particles at the membrane of
      the rough endoplasmic reticulum. In the present report we describe studies
      performed with a synthetic peptide corresponding to amino acid (aa) 160 to 169,
      the most hydrophilic C-terminal epitope of NS28. An antipeptide serum raised
      against this peptide demonstrated that this epitope was accessible in infected
      MA104 cells. Moreover, polymeric peptide was demonstrated to aggregate single
      shelled rotavirus particles. This aggregation could be almost completely
      inhibited by preincubation with monomeric peptide. Our results clearly
      demonstrate that the epitope corresponding to aa 160-169 is able to bind single
      shelled rotavirus particles.

PMID- 8572937
TI  - Low levels of poliovirus replication in primary human monocytes: possible
      interactions with lymphocytes.
AB  - To investigate the molecular mediators of poliovirus tissue tropism, the
      correlation between poliovirus replication and poliovirus receptor expression was
      examined in a primary human tissue system. Earlier work [M. Freistadt, H. Fleit,
      and E. Wimmer, Virology 195: 798-803 (1993)] showed that the cellular receptor
      for poliovirus is present in 87% of primary human monocytes and that peripheral
      blood mononuclear cells support poliovirus replication. In the current work,
      monocytes, obtained by adherence or by a novel negative selection procedure using
      specific monoclonal antibodies to lymphocyte surface antigens, supported
      poliovirus replication. However, total virus yield was low and infectious centers
      assays revealed that a minority (6%) of monocytes become productively infected.
      Viral yield from monocytes was lower than from the heterogeneous mononuclear
      cells; however, when uninfected lymphocytes were added back to infected
      monocytes, the higher viral yield was restored. The purity of the cells did not
      significantly affect the number of cells infected. These results suggest that
      more poliovirus is produced per cell from activated rather than unactivated
      monocytes. Furthermore, poliovirus replication in monocytes may reflect genuine
      in vivo replication and comprise a system in which to determine molecular
      mediators of poliovirus tissue tropism.

PMID- 8572939
TI  - A block in glycoprotein processing correlates with small plaque morphology and
      virion targetting to cell-cell junctions for an oral and an anal strain of herpes
      simplex virus type-1.
AB  - The characteristics of two clinical isolates of HSV-1 obtained from an oral (424)
      and an anal (490) lesion were compared with the highly passaged KOS strain. In
      contrast to KOS, the clinical isolates produced small plaques, were more cell
      associated and the predominant viral glycoprotein species for gC and gD in
      infected cell lysates was the precursor, high mannose glycoform. Total virus
      production in Vero cells was equivalent for the three virus strains in one-step
      growths. Pulse-chase studies of glycoprotein C processing showed a reduction in
      rate at 7.5 h post infection and a significant block in processing at 10.5 h post
      infection for 424 and 490 but not KOS. Similar results were obtained for gD. The
      significant reduction in glycoprotein processing for 424 and 490 suggests a block
      in transport of viral glycoproteins or virions to and through the Golgi
      apparatus. Extracellular virions and the cell surface, prior to cell lysis,
      contained the processed gC glycoform suggesting a competent cellular glycan
      processing system. Upon co-infection of 424 or 490 with KOS or a gC- KOS strain,
      gC was processed to levels equivalent to KOS indicating that 424 and 490 are not
      inhibitory but that an activity(s) encoded by KOS facilitates maturation of gC
      from 424 and 490. Unlike KOS infected Vero cells, virion-containing vacuoles were
      observed in the cytoplasm at 12 h p.i. and extracellular virions were
      concentrated at cell-cell junctions of 424 or 490 infected cells but not in the
      perinuclear region. These results suggest that intracellular transport of viral
      glycoproteins and virions in 424 and 490 infected cells is different from KOS
      infected cells. The reduced level of viral glycoprotein maturation, virus
      release, cell surface presence and presence of virions at cell-cell junctions are
      consistent with small plaque production in tissue culture cells.

PMID- 8572941
TI  - A highly conserved epitope on the spike protein of infectious bronchitis virus.
AB  - The predicted amino acid sequence and secondary structures of S1 of the spike
      protein (S) of infectious bronchitis viral (IBV) strains from Europe, the U.S.A.,
      and Japan were compared. An antigenic determinant that was highly conserved in
      both the primary amino acid sequence and secondary structure of all strains was
      identified between amino acid positions 240 to 255. A synthesized peptide
      corresponding to this region was found to react with all polyclonal antisera
      examined from various IBV strains and with one monoclonal antibody (MAb), 9B1B6,
      out of nine known to react with the S of Gray. The specificity of the interaction
      with MAb 9B1B6 was confirmed by competitive ELISA using bound and unbound
      peptide. Interestingly, the previously described epitope for 9B1B6 had been
      characterized as cross-reactive with several strains of IBV, as conformation
      independent but reacting only with intact whole S, and as associated with the
      functional integrity of other epitopes, including neutralizing epitopes on the S
      protein. The apparent critical functional and structural nature of this highly
      immunogenic determinant suggests a potential contribution in developing
      protective, cross-reactive subunit vaccines to IBV.

PMID- 8572940
TI  - Sequence comparison and classification of beet luteovirus isolates.
AB  - Three distinct sequence groups were found among partial nucleotide sequences of
      38 isolates of beet western yellows virus (BWYV) and beet mild yellowing virus
      (BMYV) from Europe, Iran and the USA. The first group contains both sugar beet
      and oilseed rape specific isolates, and the differentiating characteristic linked
      to this host range specificity are 2 single base pair changes in a 1,200
      nucleotide region of the genome. It is proposed that the European BWYV strains
      that can be transferred at low frequency between rape and sugar beet belong to
      this group. Also belonging to this group are the published BWYV sequences of
      Veidt et al. and of the California BWYV-ST9 isolate. The second group contains
      mostly rape-derived isolates which have an intergenic region highly distinct from
      that of group-1 isolates but similar polymerase and coat protein regions. It is
      proposed that the rape-specific BWYV isolates which cannot be transmitted to
      sugar beet belong to this group. The third group contains mostly beet-specific
      isolates from Southern Europe and Iran, and may be adapted to the Mediterranean
      climate and flora. It is distinct from groups 1 and 2 in all three genome regions
      investigated and its polymerase and intergenic regions are as much related to
      those of potato leafroll virus (PLRV) and curcurbit aphid borne yellows virus
      (CABYV) as they are to those of group-1 and group-2. On the basis of sequence
      similarities and established nomenclature it is proposed to use BWYV for groups 1
      and 2 (BWYV-1 and BWYV-2 respectively) and to use BMYV for group-3 isolates,
      which are distinct enough from the other two groups to merit a separate
      nomenclature.

PMID- 8572942
TI  - Genetic mapping of the determinants of plaque morphology of coxsackievirus B4.
AB  - The genetic determinants of plaque size of two variants of coxsackie-virus B4,
      CB4-P and CB4-V, were identified using a panel of recombinant, chimeric viruses.
      When grown in monkey kidney cells, CB4-V yielded large plaques with an average
      size of 1.0 cm while CB4-P yielded small plaques with an average size of 0.4 cm.
      Two genetic domains, the 5' untranslated region and the VP4 gene sequence,
      independently influenced plaque size. Recombinant viruses containing the CB4-P
      genetic background with point mutations in either the VP1 or VP2 coding sequences
      had small plaque phenotypes. However, two additional chimerics containing the CB4
      P genetic background with either a point mutation in the VP4 sequence or four
      substitutions in the 5' untranslated region, had large plaque phenotypes. Plaque
      size correlated with growth kinetics under single-step conditions. Large-plaque
      variants replicated to higher titers than small-plaque variants. Comparison of
      the growth kinetics of the recombinant viruses revealed some differences in viral
      replication. These data suggest that both the 5' untranslated region and arg-16
      of VP4 influence viral replication but at different stages of the replication
      cycle.

PMID- 8572943
TI  - Characterization of the US8.5 protein of herpes simplex virus.
AB  - In a previous study a novel gene designated as US8.5 was identified in the unique
      short component of the herpes simplex virus type 1 (HSV1) genome. Epitope tagging
      experiments suggested the existence of a protein encoded by this gene in HSV1
      infected cells. To further analyze the US8.5 gene product and function, a rabbit
      polyclonal antiserum was raised against a recombinant beta-galactosidase-US8.5
      fusion protein expressed in E. coli. This antiserum reacted specifically with a
      19 kDa protein in HSV1(F) infected cells as shown by immunoblotting and
      immunoprecipitation experiments. In addition, using the same antiserum a 21 kDa
      protein was detected in lysates from cells infected with HSV2(G), which was most
      likely the HSV2 homolog of US8.5. Kinetic studies indicated that US8.5 is
      expressed as gamma 1 gene. In addition, the US8.5 protein was immunoprecipitated
      with the anti-US8.5 serum from 32P-labeled lysates of Vero cells infected with
      HSV1, demonstrating that the protein is phosphorylated. Immunofluorescence
      studies localized the US8.5 protein to the nucleoli of HSV1 infected cells.

PMID- 8572945
TI  - Both SU and TM env proteins are responsible for monkey cell tropism of simian
      immunodeficiency virus SIV mac.
AB  - While simian immunodeficiency virus (SIV) derived from an infectious molecular
      clone pMA239 is tropic and pathogenic for monkeys, the virus derived from another
      infectious clone pMA142 does not replicate in monkey cells. To determine genetic
      sequences responsible for this tropism, a series of recombinant clones were
      constructed from pMA142 and pMA239. The determinant in pMA239 was mapped within
      regions encompassing the env gene. Viruses, which carry the 239 env gene encoding
      surface and/or transmembrane proteins, were tropic for monkey cells.

PMID- 8572944
TI  - Spread of Venezuelan equine encephalitis virus in mice olfactory tract.
AB  - Spread of Venezuelan equine encephalitis (VEE) virus and damage of the central
      nervous system (CNS) in mice infected by respiratory route was studied. Virus
      concentration in organs and blood, "dose-effect" relationships, and
      ultrastructural lesions in various tissues were examined in immune and normal
      mice. We showed, via three independent methods--characteristic curve
      investigations, tissue virus concentration dynamics, and ultrastructural methods-
      the spread of VEE virus through the olfactory tract into the brain of immune
      mice. From these experiments it was concluded that in case of respiratory
      challenge VEE virus can enter the CNS of normal mice by both vascular and
      olfactory pathways, while in immune mice the main route is olfactory.

PMID- 8572946
TI  - Genome homology and superinfection immunity between temperate and virulent
      Lactobacillus delbrueckii bacteriophages.
AB  - The presence of short homologous DNA segments along the genomes of the temperate
      phage mv4 and the virulent phages LL-H, LL-K and JCL1032 of Lactobacillus
      delbrueckii was demonstrated with Southern hybridizations. One of these segments,
      the 2,817 nt MIS element of phage mv4, was further characterized by nucleotide
      sequence analysis and by superinfection immunity studies.

PMID- 8572947
TI  - Nucleotide and deduced amino acid sequence of the 3' end of the BYMV-MI genome.
AB  - We have cloned and sequenced cDNA transcribed from the 3' 1,239 nucleotides of
      the genomic RNA of a Western Australian isolate (MI) of bean yellow mosaic
      potyvirus (BYMV). This sequence contains 246 nucleotides of the NIb (replicase)
      gene and 819 nucleotides representing the entire coding region of the viral coat
      protein gene, followed by a 3' non-coding region of 174 nucleotides. The coding
      region of the coat protein gene is identical in length (273 amino acids) to that
      already reported for other isolates of this virus. The sequence identities
      obtained for BYMV-MI and published sequences of BYMV isolates range between 85%
      and 92% for the coding region of the coat protein and 90% to 98% for the 3' non
      coding region. Likewise, the region of the NIb gene sequenced shows 99% and 97%
      sequence identity in the deduced amino acid and the nucleotide sequences,
      respectively.

PMID- 8572948
TI  - Development of polymerase chain reaction for specific identification of epizootic
      hemorrhagic disease virus serotype 1.
AB  - The diagnostic potential of the polymerase chain reaction (PCR) for specific
      identification of epizootic hemorrhagic disease virus serotype 1 (EHDV-1) in cell
      culture and clinical specimens was evaluated. Using oligonucleotide primers,
      selected from genome segment 2 of EHDV-1 (New Jersey strain), the PCR-based assay
      resulted in a 862 base pair (bp) PCR product. EHDV-1 RNA from United States
      prototype serotype 1 and a number of EHDV-1 field isolates, propagated in cell
      cultures, were detected by this PCR based assay. The specific 862 bp PCR products
      were visualized on ethidium bromide-stained agarose gel. Identity of the PCR
      product was confirmed by chemiluminescent hybridization with non radiolabelled
      internal probe. Using chemiluminescent hybridization, the sensitivity of the PCR
      assay was 1.0 fg of virus RNA (equivalent to 60 virus particles). Amplification
      product was not detected when the PCR-based assay was applied to RNA from EHDV
      serotype 2 (EHDV-2); the United States bluetongue virus (BLU) prototypes
      serotypes 2, 10, 11, 13, and 17; total nucleic acid extracts from uninfected BHK
      21 cell; or blood cells from calves and deer that were EHDV-seronegative and
      virus isolation negative. Application of this EHDV-1 PCR-based assay to clinical
      samples resulted in detection of EHDV-1 RNA from blood samples, collected from a
      calf experimentally infected with EHDV-1. The described PCR-based assay provides
      a simple, rapid, sensitive, specific and inexpensive method for specific
      identification of EHDV-1 infection in susceptible ruminants.

PMID- 8572949
TI  - Nucleotide sequence of a 1446 base pair SalI fragment and structure of a novel
      early gene of Leucania separata nuclear polyhedrosis virus.
AB  - A 1446 bp SalI fragment of LsNPV was sequenced by the silver staining method, and
      two large open reading frames (ORFs, ORF1 and ORF2) were found, both contain
      typical characteristics of the 5' regulatory elements of baculovirus early genes.
      ORF1 is 345 bp long with the capacity to encode a putative protein of 114 amino
      acid residues with MW about 13 kDa and was designated p13 gene, ORF2 comprises
      248 bp from the 3' end of the fragment. In the untranslated region (UTR) of ORF1,
      a 33 bp mini cistron (ORF3), a core recognition sequence (CGTCG) for many bHLHzip
      transcription factors and a late promoter sequence TTAAG are present. In the UTR
      of ORF2, two host transcription factor binding elements (CACGTG and GATA motif)
      and two CGT motifs were found. Some regular leucine zipper-like structures,
      designated leucine trans-conformation structure and LVT repeat, were found near
      the N-terminus and the middle of p13 protein. The leucine trans-conformation
      structure that is near the N-terminus consists of 4 leucines and 7 other amino
      acids between every two leucines, and every leucine is located at a conformation
      shift point of the predicted secondary structure of the p13 protein. In LVT
      repeat, L-6aa-V-6aa-T-6aa is repeated once. The functions of those structures
      remain unclear, and the two ORFs, not found in the genome of Autographa
      californica nuclear polyhedrosis virus, are possibly two new genes.

PMID- 8572950
TI  - A century of veterinary vaccinology: the Merieux initiative.

PMID- 8572951
TI  - Can we develop a totally implantable rotary blood pump?

PMID- 8572952
TI  - Mechanically induced blood trauma: are the relevant questions already solved, or
      is it still an important field to be investigated?

PMID- 8572953
TI  - System considerations favoring rotary artificial hearts with blood-immersed
      bearings.
AB  - Hydrodynamic blood pumps provide such advantages as not requiring an air vent or
      compliance chamber as well as a great reduction in mechanical complexity with the
      potential for very long durability. The detailed design of their bearings is
      emerging as the single most important determinant of long-term success. Three
      categories of bearings include remote force, such as magnetic suspension; blood
      isolated, which require a shaft seal; and blood-immersed using either mechanical
      or hydrodynamic support. Blood-immersed bearings permit maximum simplification
      and miniaturization of the entire system, require no flush fluid, and require no
      electronics as with magnetic suspension. The Jarvik 2000 heart represents an
      example of their potential. The intraventricular titanium pump (25 mm diameter,
      25 cc, 85 g), uses blood flow through the motor air gap with blood-immersed
      bearings. The longest in vitro bearing durability test is ongoing at
      20,000,000,000 revolutions with minimal wear (3 years at 15,000 rpm). In vivo
      results include 5-month calf survival, no thromboembolism, plasma Hb 2-5 mg%, and
      power under 10 W.

PMID- 8572954
TI  - Total erythrocyte destruction time: the new index for the hemolytic performance
      of rotary blood pumps.
AB  - To date an index of hemolysis is the only parameter to evaluate in vitro the
      hemolytic properties of blood pumps. However, this index does not reflect the
      sublethal conditions of erythrocytes. In this paper, a new concept, the total
      destruction of erythrocytes, to indicate traumatic features on erythrocytes is
      proposed. Five paired long duration in vitro hemolysis tests were conducted using
      the BioMedicus pump; BP80, and the Nikkiso pump, HMS12. The pumps ran until
      either a sudden change in blood color to dark red was noted or the pumps ran for
      over 24 h. At a certain point, the plasma-free hemoglobin levels suddenly and
      dramatically increased in each experiment except one Nikkiso case. At a certain
      point in time, the destruction of most erythrocytes suddenly and simultaneously
      occurred. We call this phenomenon total destruction of erythrocytes and define
      the pumping duration required to raise the level of the plasma-free hemoglobin to
      50% of the total hemoglobin as total destruction time. Although there is no
      statistical difference in the normalized index of hemolysis between the two
      pumps, the total destruction time of the BioMedicus pump is significantly shorter
      than that of the Nikkiso pump. It appears that an accumulation of sublethal
      damage on erythrocytes resulted in the decrease of the hemolytic threshold of the
      entire erythrocyte and also resulted in a sudden entire destruction of
      erythrocytes.

PMID- 8572955
TI  - A mathematical model for shear-induced hemolysis.
AB  - The time-varying history of stress exposure within a rotary blood pump makes it
      difficult to arrive at a quantifiable design criterion for predicting cell
      traumatization. Constant stress experiments have revealed that there is a
      threshold stress level above which damage to blood cells occurs depending upon
      the time of exposure. The shear stress history experienced by cells within a
      rotary blood pump, however, is highly unsteady. In order to better predict cell
      trauma under these realistic conditions, a mathematical damage model based on a
      concept of "damage accumulation" has been developed. This model is evaluated
      within the context of red cell trauma. Experimental results support the
      hypothesis that the rate of damage accumulation increases nonlinearly with the
      stress level as well as the age of the cell.

PMID- 8572956
TI  - Model for a general mechanical blood damage prediction.
AB  - Knowledge of the correlation between mechanical loading of formed blood elements
      and the amount of their destruction is important for the prediction of blood
      trauma in artificial circulatory devices as well as in natural circulation. A
      hemodynamic assessment and optimization of artificial organs to minimize trauma
      could be undertaken in the design phase given a comprehensive mechanical blood
      damage model. A theory to determine blood trauma theoretically as a combination
      of a mechanical loading analysis and a phenomenological blood damage resistance
      hypothesis is presented. Arbitrary stress-time functions of blood particles
      predicted by flow analysis are reduced to a set of simple time functions for
      which the damage behavior may, in principle, be obtained from mechanical blood
      damage tests. A classification of those stress functions into damaging and
      nondamaging parts is followed by an overall trauma prediction considering
      cumulative effects by means of a damage accumulation hypothesis. Theoretical
      determination of blood destruction caused by mechanical stresses in a centrifugal
      pump is one possible application of the proposed theory. The strategy of
      hemolysis prediction is demonstrated for the Aries Medical Isoflow Pump.
      Irregular stress-time loading functions of particles passing the pump domain
      obtained by three-dimensional numerical flow simulations were reduced and
      classified into harmonic components. To relate these functions to their hemolytic
      response can only be done in a qualitative manner since blood damage behavior
      under transient stress loading has not been sufficiently investigated. Accurate
      prediction of blood trauma using the proposed theory will require detailed study
      of the influence of frequency and amplitude of harmonic stress loading on formed
      blood elements.

PMID- 8572957
TI  - Three-dimensional numerical prediction of stress loading of blood particles in a
      centrifugal pump.
AB  - The successful use of centrifugal pumps as temporary cardiac assist devices
      strongly depends on their degree of blood trauma. The mechanical stress loading
      experienced by cellular components on their passage through the pump is a major
      cause of blood trauma. Prediction of the mechanical stresses will assist
      optimization of pump design to minimize hemolysis and platelet activation. As a
      theoretical approach to this task., the determination of the complete three
      dimensional (3D) flow field including all regions of high shear stress is
      therefore required. A computational fluid dynamics (CFD) software package,
      TASCflow, was used to model flow within a commercially available pump, the Aries
      Medical Isoflow Pump. This pump was selected in order to demonstrate the ability
      of the CFD software to handle complex impeller geometries. A turbulence model was
      included, and the Newtonian as well as the Reynolds stress tensor calculated for
      each nodal point. A novel aspect was the assignment of scalar stress values to
      streaklines representing particle paths through the pump. Scalar stress values
      were obtained by formulating a theory that enables the comparison of a three
      dimensional state of stress with a uniaxial stress as applied in all mechanical
      blood damage tests. Stress loading-time functions for fluid particles passing
      inlet, impeller, and outlet domains of the pump were obtained. These showed that
      particles undergo a complex, irregularly fluctuating stress loading. Future blood
      damage theories would have to consider an unsteady stress loading regime that
      realistically reflects the flow conditions occurring within the pump.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8572958
TI  - Fluid mechanics of the stagnation point flow chamber and its platelet deposition.
AB  - The interaction of flow and thrombus generation often is a crucial question for
      the engineer working in the field of artificial organs. However, this interaction
      is only incompletely known, and quantitative data under well-defined experimental
      conditions are especially rare. These can be attained with the stagnation point
      flow chamber. This flow model applies platelet-rich plasma (PRP) as fluid. Its
      flow conditions are assessed with the help of computational fluid mechanics. In
      addition, the concept of the boundary layer is introduced, which permits
      assessment of the platelet flow along the wall. The results of the experiment
      indicate that platelets are deposited at a defined shear rate.

PMID- 8572959
TI  - Biomaterials for rotary blood pumps.
AB  - Rotary blood pumps are used for cardiac assist and cardiopulmonary support since
      mechanical blood damage is less than with conventional roller pumps. The high
      shear rate in the rotary pump and the reduced anti-coagulation of the patient
      during prolonged pumping enforces high demands on the biocompatibility of the
      materials in the pump in order to prevent thrombus formation. Materials with a
      very hydrophobic character appear to adsorb much thrombin and induce a
      conformational change of fibrinogen, resulting in a surface with a high affinity
      for platelet interaction. Furthermore, high shear forces of 120 dyne-s-cm2 in
      rotary pumps induce platelet release and platelet aggregation. Thus, hydrophobic
      materials and high shear rates should be prevented to avoid thrombus formation in
      rotary blood pumps.

PMID- 8572960
TI  - Computational flow optimization of rotary blood pump components.
AB  - In an effort to improve and automate the fluid dynamic design of rotary blood
      pumps, a coupled computational fluid dynamics (CFD) shape optimization
      methodology has been developed and implemented. This program couples a finite
      element flow simulation with a gradient-based optimization routine to modify
      automatically the shape of an initial candidate blood path, according to a
      variety of desired fluid dynamic criteria, including shear stress,
      vorticity/circulation, and viscous dissipation. Preliminary results have led to
      both intuitive and nonintuitive transformations of the initial blood flow paths
      for both internal and external flows. This application of computer design
      optimization offers the ability to explore a much broader design space much more
      efficiently than would be possible with traditional parametric methods. It is
      believed that this computer tool can assist developers of rotary blood pumps in
      designing blood-wetted components that minimize thrombosis and hemolysis while
      simultaneously providing maximum flow performance.

PMID- 8572961
TI  - Comparative hemolysis tests of rotary blood pumps.
AB  - At present, hemolysis is one of the most important characteristics used to
      evaluate rotary blood pumps. However, the conditions of testing procedures in
      various research centers differ considerably. We proposed to conduct the
      experiments under conditions similar to those from clinical applications of
      arterial pumps in extracorporeal perfusion. Proceeding from these considerations,
      the following parameters of Hemolysis (H) testing were adopted: output, 6 L/min;
      difference of pressure, 300 mm Hg; initial hematocrit, 30 mg%; and initial
      hemolysis (PHbo) < 5 mg%. The channel pump IBP80 designed on the basis of the
      BP80 was tested using fresh human blood. The experimental results indicate that
      the H level due to the use of the IBP80 is 2-3 times less than H for the BP80. H
      dependence on the difference of pressure in the range between 200 and 300 mm Hg
      was noted for the BP80, which can be accounted for by the transition of the
      laminar conditions of flow to turbulence. According to the results of the
      hydrodynamic efficiency evaluation, the IBP80 is twice as efficient as the BP80.

PMID- 8572962
TI  - Seal-less centrifugal blood pump with magnetically suspended rotor: rot-a-flot.
AB  - Limitations of current centrifugal blood pumps are related to heat generation of
      bearings and leakage of seals, to dead water zones, and to poor efficiency. A new
      concept is proposed in this paper to ameliorate these problems based on a
      miniaturized magnetic drive, and a prototype is introduced. The pump rotor is
      suspended and driven by a radial permanent magnetic field that stabilizes the
      impeller in 4 of the 6 spatial degrees of freedom and allows it to be top-spun on
      a single blood-flushed pivot bearing with minimal load and friction. A shrouded
      impeller with an open center and 4 logarithmically curved channels is run inside
      a cone-and-plate-type housing with a spiral volute chamber. In vitro testing was
      performed comparing this design with the BioMedicus, St. Jude, and Sarns pumps.
      The prototype is demonstrated to have the smallest internal volume (35 ml),
      surface (190 qcm), and passage time (0.5 s at 4 L/min), as well as the highest
      hydraulic efficiency (up to 0.4) of all devices studied.

PMID- 8572963
TI  - Design of a centrifugal blood pump with magnetic suspension.
AB  - A new concept blood pump, whose impeller is suspended by permanent magnets and a
      mechanical pivot without seals or ball bearings, is presented in this paper. The
      primary aim of the blood pump is an application to implantable artificial hearts.
      The prototype model is of a centrifugal type with a four-vaned semiopen impeller
      50 mm in diameter. Since this mechanism has no seals or ball bearings, flow
      stagnation or heat generation that might cause blood cell denaturation is
      expected to be small. The results of performance testing for the prototype model
      2 were satisfactory regarding pump head and efficiency. The radial-suspension
      magnets and the magnetic coupling were stable. As a result, the present mechanism
      has been verified to be a candidate applicable to implantable artificial hearts.

PMID- 8572964
TI  - Recent studies of the centrifugal blood pump with a magnetically suspended
      impeller.
AB  - We have been developing a centrifugal blood pump with a magnetically suspended
      impeller. To improve pump efficiency, we investigated the pump performances of
      many kinds of impeller vanes and diffusers, as well as the flow in the gap
      between the impeller discs and the pump housing. We found the vanes and the
      diffusers with high pump efficiency; however, high efficiency does not mean low
      hemolysis. It seems important to prevent generation of small-sized eddies with
      high shear stress. Hemolysis tests are carried out to find the optimal vane
      profile and gap clearance. The index of hemolysis and temperature change of our
      pump is better than those of the Biopump. Short-term in vivo studies show that
      the layer of white thrombi adheres to the machined rough surface of
      polycarbonate, which composes the narrow gap (0.2 mm) between the impeller and
      the pump wall, but a smooth surface coated with silicon prevents adhesion of that
      layer.

PMID- 8572965
TI  - In vitro analysis of the floating mode phenomenon in the Free Impeller Gyro Pump.
AB  - The Free Impeller Gyro Pump was designed based on a new concept of free impeller,
      in which the rotational shaft and the mechanical bearings were completely
      eliminated from the impeller. Due to this characteristic design, a phenomenon
      occurred in which the impeller lifted off the bottom of the pump housing in a
      certain range of pumping conditions during the initial in vitro studies (floating
      mode). We studied this floating mode in detail using a Hall effect position
      sensor to monitor the impeller position. A Hall sensor signal recorded on the
      strip chart, which represents the distance between the impeller top and the pump
      ceiling, proved the existence of the floating mode. By analyzing the data in
      detail, it was also verified that the floating mode was composed of three
      subdivided phases: latent, transitional, and dominant. Furthermore, stability of
      the impeller rotation in the floating mode against the change of pump orientation
      was also exhibited in this study. These results suggests that the Free Impeller
      Gyro Pump should possess high antithrombogenicity, atraumatic features, no
      bearing wear, and stable performance when operated within the range of the
      floating mode.

PMID- 8572966
TI  - An implantable seal-less centrifugal pump with integrated double-disk motor.
AB  - Thrombus formation and sealing problems at the shaft as well as the compact and
      efficient design of the driving unit have been major difficulties in the
      construction of a long-term implantable centrifugal pump. To eliminate the
      problems of the seal, motor size, and efficiency, two major steps were taken by
      modifying the Vienna implantable centrifugal pump. First, a special driving unit
      was developed, in which the permanent magnets of the motor themselves are used
      for coupling the force into the rotor. Second, the rotor shaft in the pumping
      chamber was eliminated by adopting a concept recently presented by Ohara. The
      rotor is supported by 3 pins, which run on a carbon disk, whose concave shape
      leads to stabilization. The device has the following specifications: size: 65 mm
      (diameter) by 35 mm (height), 101 cm3; priming volume 30 cm3, 240 g; and a 6-pole
      brushless double disk DC motor. The required input power of the described
      prototype is 15 W at 150 mm Hg, 5 L/min (overall eta = 11%), and has an in vitro
      index of hemolysis (IH) of 0.0046 g/100 L. The test for in vitro thrombus growth
      exhibited far less thrombus formation in the new design than in designs with
      axles. In conclusion, the design of a special driving unit and the elimination of
      the axle led to the construction of a small pump with very low blood
      traumatization.

PMID- 8572967
TI  - Concept, realization, and first in vitro testing of an intraarterial microaxial
      blood pump.
AB  - Intravascular operating microaxial pumps have been clinically introduced
      (Hemopump 21; Hemopump 14) and have proven to be useful tools for cardiac assist.
      Due to device-related complications that are associated with the drive concept of
      an extracorporeal motor and a flexible drive shaft cable, a new pump concept is
      presented and has been refined in the development process. The cable is replace
      by a proximally attached drive unit and an extracorporeal power supply. In
      addition to ongoing hydrodynamic studies of the flow inside the pump and
      improvements of the overall hydraulic performance, a microelectric motor was
      realized and integrated. In vitro tests revealed the feasibility of such a
      concept.

PMID- 8572968
TI  - Development of an axial flow ventricular assist device: in vitro and in vivo
      evaluation.
AB  - A collaborative effort between Baylor College of Medicine and NASA/Johnson Space
      Center is underway to develop an axial flow ventricular assist device (VAD). We
      evaluated inducer/impeller component designs in a series of in vitro hemolysis
      tests. As a result of computational fluid dynamic analysis, a flow inducer was
      added to the front of the pump impeller. According to the surface pressure
      distribution, the flow inducer blades were connected to the impeller long blades.
      This modification eliminated high negative pressure areas at the leading edge of
      the impeller. Comparative studies were performed between inducer blade sections
      that flowed smoothly into the impeller blades (continuous blades) and those that
      formed discrete separate pumping sections (discontinuous blades). The
      inducer/impeller with continuous blades showed significantly (p < 0.003) lower
      hemolysis with a normalized index of hemolysis (NIH) of 0.018 +/- 0.007 g/100 L
      (n = 3), compared with the discontinuous model, which demonstrated an NIH of
      0.050 +/- 0.007 g/100 L (n = 3). The continuous blade model was evaluated in vivo
      for 2 days with no problems. One of the pumps evaluated ran for 5 days in vivo
      although thrombus formation was recognized on the flow straightener and the
      inducer/impeller. As a result of this study, the pump material was changed from
      polyether polyurethane to polycarbonate. The fabrication method was also changed
      to a computer numerically controlled (CNC) milling process with a final vapor
      polish. These changes resulted in an NIH of 0.0029 +/- 0.0009 g/100 L (n = 4),
      which is a significant (p < .0001) value 6 times less than that of the previous
      model.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8572969
TI  - Considerations and problems in the development of the mini-spindle pump.
AB  - The premise for the development of the mini-spindle pump, planned as an
      implantable device for assisted circulation, was to transport 4 L of water/min in
      mock circulation with a speed of 12-15,000 rpm against an afterload of 90 mm Hg.
      After calculations, the resulting first prototype had a spindle rotor with 3
      threads (outer diameter, 18 mm; inner diameter, 6.2 mm; length, 45 mm) in a U
      shaped housing, driven by an electric motor with a cooling system. In mock
      circulation, this pump moved 7.8 L of water/min at 18,000 rpm. To avoid animal
      experiments, its influence on the blood was tested in a Maxima oxygenator. The
      device circulated 4.2 L of blood/min with the same speed. Because of its high
      traumatic hemolysis rate (> 250 mg% of free hemoglobin after 7 h of pumping), the
      rotor was modified, first without effect at 2.5 threads and then at 4 threads. In
      addition, in this third prototype, the flow direction was reversed. This
      prototype was more effective (4.3 L of blood/min at 12,000 rpm in the oxygenator)
      and the hemolysis rate, after a pumping duration of 8 h, could only be reduced to
      180 mg% of free hemoglobin. As a result, a fourth prototype was developed (i.e.,
      the U-shape of the housing was abandoned). This device functioned better than the
      third prototype (4.5 L of blood/min at 12,000 rpm in the oxygenator), but the
      blood trauma increased (220 mg% of free hemoglobin after 7 h of
      pumping).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8572970
TI  - Flow visualization study on centrifugal blood pump using a high speed video
      camera.
AB  - Flow visualization is widely applied to evaluate rotary blood pumps; however, it
      is very difficult to visualize flow near the vanes of centrifugal blood pumps
      because the rotational speed of the impeller is usually several thousand rpm. In
      this study, a tracer method with a high speed video camera that can take more
      than 2,000 frames/s was utilized for flow visualization together with computer
      assisted image measurement. This method visualized the complex secondary flow
      pattern near the vanes of the impeller, such as the vortex and recirculation. It
      also visualized the enhanced washout effect by the secondary washout vanes on the
      backside of the impeller. The proposed method was effective to analyze the flow
      pattern in the centrifugal blood pump by providing useful information for better
      design of the pump hemolysis and thrombus formation.

PMID- 8572971
TI  - An improved left ventricular cannula for chronic dynamic blood pump support.
AB  - Ventricular unloading with dynamic blood pumps can be markedly affected by the
      geometry of the cannula tip within the ventricular chamber. Due to the ability of
      these pumps to develop significant negative inflow pressure, existing cannula
      tips designed for passively filling blood pumps can be predisposed to inflow
      occlusion by intraventricular anatomic structures. A novel "trumpet" mouth
      cannula was constructed to overcome this limiting problem. This design was based
      on two criteria: to provide additional stenting to the ventricular apex, and to
      assure placement of the tip opening relative to the endocardial surface. This
      prototype cannula was evaluated in vivo against conventional caged, blunt, and
      tapered designs to assess anatomic and hemodynamic interaction within the
      ventricular apex. Post mortem examination revealed the inflow tract to be devoid
      of myocardial obstruction in all cases. These initial studies indicate that a
      trumpet mouth cannula can provide satisfactory hemodynamic performance required
      by dynamic blood pumps.

PMID- 8572972
TI  - Totally implantable ventricular assist system using a vibrating flow pump.
AB  - A totally implantable ventricular assist system (VAS), including a drive system
      and a percutaneous electric energy transmission system, was developed and
      evaluated in acute animal experiments using adult goats. This newly designed VAS
      mainly consists of a vibrating tube, coils, magnets, and a jelly-fish valve as
      the outlet valve. For energy transmission, a new implantable transmitter with a
      plain weave structure was proposed as a noncontacting transform by using the
      spinal amorphous magnetic fibers. The fluid mechanical and hemodynamic properties
      and the efficiency of the energy transmission system were evaluated in acute
      animal experiments using healthy adult goats. This vibrating electromagnetic
      artificial heart (AH) could generate more than 10 L/min as output volume, with 10
      Hz vibration using 20 volts as supplied voltage. The total efficiency of the
      percutaneous energy transmission system was 76%, and temperature increases were
      within the acceptable range, suggesting the usefulness of our newly developed
      implantable VAS.

PMID- 8572973
TI  - A preliminary flow visualization study in a multiple disk centrifugal artificial
      ventricle.
AB  - Flow patterns in a multiple disk centrifugal pump were analyzed so that the
      device could be incorporated as a ventricular assist or a bridge-to-transplant
      device. The pump operates either in pulsatile or steady flow modes with the
      ability to change modes within a fraction of a second. The pump was tested on a
      mock circulatory system consisting of an arterial fluid capacitor, a systemic
      resistor, and a venous capacitor. Arterial volume flow rate, arterial pressure,
      inlet (venous) pressure, and pump rotation speed are continually monitored. A
      glycerin/water solution is used as a blood analog. Flow visualization was
      performed with a 3 mW yellow laser, sheet lens, neutrally buoyant amberlite
      particles, and both still and motion picture photography. Flow patterns matched
      theoretical predictions very well; inlet flow spread radially outward through the
      disk annular spaces while propelled by shear and centrifugal forces.

PMID- 8572974
TI  - Preliminary design and optimization of an ECC blood pump by means of a parametric
      approach.
AB  - This study concerns the development of an analytical parametric model of a
      centrifugal disk pump. The advantage of this kind of approach is to have an
      adaptable tool as a first step for the design of a pump device. The method allows
      the evaluation of the velocity profiles and the shear stresses within the
      impeller disks in the flow domain along with the performance of the device in
      terms of torque, mechanical power, power loss, head-flow performance, pump
      efficiency, and hemolytic index. Some simplifying hypotheses are assumed: steady
      state condition, laminar flow, Newtonian and incompressible fluid. The radial
      velocity profiles are assumed to be uniform and the flow cross-sectional area is
      assumed to be constant along the radius. The influence of the housing and
      secondary flows caused by recirculation are neglected. To test the approach
      reliability, the model was used to simulate a pump with the following
      characteristics: an external and internal radius of 50 mm and 5 mm, respectively,
      and a channel height of 2.5-0.25 mm (h) from inlet to outlet section. The angular
      velocity omega was varied in the range 500-3,000 rpm. The flow rate has been
      varied from 1 to 5 L/min. The results show that when the flow rate is increased,
      head performances obtained using this pump model vary from 411 to 100 mm Hg, and
      its efficiency varies from 48 to 15%. A parallel simulation has been carried out
      by means of a Finite Element Method model with an angular velocity equal to 2,000
      rpm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8572975
TI  - Basic study to develop the undulation pump for practical use:
      antithrombogenicity, hemolysis, and flow patterns inside the pump.
AB  - The undulation pump (formerly called the precessional displacement pump) is a
      continuous flow displacement-type blood pump that is being developed as an
      implantable total artificial heart. A new undulation pump was developed for
      chronic use and was examined with animal experiment and flow visualization
      studies. In the animal experiment using a left ventricular bypass in goats,
      severe hemolysis occurred. After driving for 12 h, thrombus formation inside the
      pump was found. In the flow visualization studies, the flow pattern showed that
      the flow inside the pump was a very complicated turbulent flow. Improvement of
      hemolysis and thrombus formation is important to realize implantable total
      artificial hearts using undulation pumps.

PMID- 8572976
TI  - New version of flow-transformed pulsatile total artificial heart with no
      electrical switching valve.
AB  - The flow-transformed pulsatile total artificial heart (FTPTAH) is a new pulsatile
      total artificial heart that consists of a single continuous flow rotary blood
      pump and blood flow switching valves. It can perfuse the pulmonary and the
      systemic circulation alternately with pulsatile flow. A new version of the
      FTPTAH, which consists of one undulation pump (UP), 4 jellyfish valves, and a
      compensatory chamber, has been proposed. The UP is a reversible continuous flow
      blood pump, and flow transformation is caused by switching the direction of the
      motor rotation so that no electrical flow switching valve is needed. A prototype
      model could perfuse alternately pulmonary and systemic circulation with 3.0 L/min
      in a mock circulation. Unoxygenated blood in the UP at the end of pulmonary
      circulation will be stored in the compensatory chamber by shifting a flexible
      membrane to the direction of the left atrium (LA); therefore, the blood is not
      sent to the systemic circulation.

PMID- 8572977
TI  - In vitro evaluation of a pulsatile assist device for a centrifugal pump using a
      new principle.
AB  - To induce a pulsatile flow in a centrifugal pump, we developed a new device
      (pulsatile assist device for centrifugal pump: PADCP) using a new concept. This
      device consists of a flexible polyurethane tube with an air chamber which is
      connected to the arterial side of the centrifugal pump circuit directly. A mock
      circulation system was used for evaluation of this PADCP. Thirty to 40 mm Hg of
      pulse pressure was obtained under 3-6 L/min of flow rate. By increasing the
      driving pressure of the PADCP from 200 to 600 mm Hg in a mock system, 4-48 mm Hg
      of pulse pressure was gained accompanied by a decrease in pump flow and increased
      left atrial pressure. The decreased pump flow and increased left atrial pressure
      were recovered easily by increasing the flow rate of the centrifugal pump.
      Pressures at the proximal site of the PADCP were less than 500 mm Hg. The PADCP
      was useful to induce a pulsatile flow in a centrifugal pump.

PMID- 8572978
TI  - Pulsatile total artificial heart using a reversible rotary pump.
AB  - A pump circuit was assembled and examined for use as an implantable artificial
      heart. The circuit consisted of a gear pump and 4 artificial heart valves. Mitral
      and pulmonary arterial valves were placed at the inflow port of the pump, and
      aortic and tricuspid valves were placed at the outflow port. The mitral and the
      tricuspid valves were connected to each reservoir at 10 mm Hg, and the aortic and
      the pulmonary arterial valves were connected to the head tanks at 80 and 20 mm
      Hg, respectively. The pump discharged pulsatile flows into both systemic and
      pulmonary arteries alternately by switching the direction of rotation
      periodically. Because the rated discharge was 1.7 L/min for the gear pump used,
      the measured flow rate was 0.8-0.75 L/min at a heart rate of 60-110 bpm.

PMID- 8572979
TI  - Experimental study of physiological advantages of assist circulation using
      oscillated blood flow.
AB  - To estimate the effect of oscillated blood flow on hemodynamics in an awake
      condition, left ventricular assist circulation using oscillated blood flow was
      performed on 3 adult goats as chronic animal examination. A vibrating flow pump
      (VFP) was used for generating high-frequency oscillated flow. The blood flow rate
      of assisted circulation was approximately 1.0 L/min, and the driving frequency of
      VFP was 25 Hz. Systemic vascular resistance and arterial impedance were
      calculated in this study. Systemic vascular resistance during assist circulation
      was decreased compared with that without assistance. Oscillated blood flow may be
      effective in decreasing vascular resistance. Moreover, it was suggested from the
      study of arterial impedance that motive characteristics of the vascular wall
      against changing blood pressure may keep their normal reaction. Therefore,
      oscillated blood flow may be used for left ventricular assist circulation as
      concluded from the study of the characteristics of blood vessels.

PMID- 8572980
TI  - A clinical monitoring system for centrifugal blood pumps.
AB  - In clinical application of rotary blood pumps, flow obstruction as a result of
      suction of the inflow cannula, kinking of tubing, or thrombus formation occurs
      quite frequently. Early detection of such problems is essential to avoid
      hemolysis, tissue degradation, or release of thrombi to the patient. A program
      was developed for automatic observation of pump performance, tubing resistance,
      and suction effects, which requires only the measurement of already available
      parameters (i.e., pump speed, pump flow, aortic pressure). The software is based
      on Visual-C and provides a user surface formatted in Windows. Pump flow, its time
      derivate, and the relationship between the pulsatile component and the mean graft
      flow are observed to detect suction in the left atrium. Furthermore, the
      generated pressure head is predicted from pump speed, graft flow, and the
      resistance of tubing/cannula and compared with the actually measured aortic
      pressure. An alarm sounds if a given limit between prediction and measurement is
      exceeded. In a mock circulation, suction events were detected in more than 95%
      with a mean deviation of actual aortic pressure from its predicted value of less
      than 5%. For in vivo application, even incomplete suction could be detected
      reliably in more than 90% of events. This system improves and standardizes
      monitoring of pump performance; it should therefore lead to greater safety during
      application of such devices.

PMID- 8572981
TI  - Development of an autoflow cruise control system for a centrifugal pump.
AB  - To improve the ease of driving a centrifugal pump that is afterload dependent, we
      have developed an automatic flow control system for the Terumo Capiox centrifugal
      pump system. This system consists of an autoflow cruise control system with a
      safety cutoff. The Capiox Pump Console 3000 was controlled by a personal computer
      through a serial communication line. In the usual manual mode, the motor speed
      knob works as a pump speed control, and in the autoflow mode, the same knob works
      as a blood flow rate control. After selecting and obtaining the desired flow
      rate, the mode was changed from manual to autoflow mode. In the autoflow mode,
      the computer compares the desired flow rate with the actual flow measured by an
      ultrasonic Doppler flowmeter and adjusts the motor rotational speed accordingly.
      During both in vivo and in vitro testing, this autoflow mode was able to return
      the changed flow that was disrupted by either clamping and declamping of the
      tubing or by the bolus injection of a vasomotor drug to the selected flow rate
      within 10 s without any significant fluctuation. In conclusion, the newly
      developed computer controlled autoflow system was able to produce a reliable and
      effective flow regulation for a centrifugal pump.

PMID- 8572982
TI  - An artificial neural network-based noninvasive detector for suction and left
      atrium pressure in the control of rotary blood pumps: an in vitro study.
AB  - Rotary blood pumps are used in clinical applications to assist circulation via
      pumping blood from the left atrium to the aorta. Negative inflow pressures at
      high flow rates can cause suction of the cannula in the left atrium with
      deleterious effects on the atrial wall, the blood, and the lung. Therefore,
      stable and reliable detection of suction and the prediction of the left atrium
      pressure (LAP) would be of major interest for the control of these pumps. This
      work reports about an in vitro study of such a detector based on artificial
      neural networks (ANN). In the first project phase, an ANN was used to estimate
      the LAP based on pump speed, pump flow, and aortic pressure, obtained from a mock
      circulation. The inputs for the ANN were 11 characteristic values computed from
      these three parameters. In the second phase, another ANN was trained to classify
      various system states, such as suction, danger of suction (a state close to
      actual suction), and no suction. The first ANN was able to estimate the LAP with
      an accuracy of +/- 1.8 mm Hg. The discrimination of suction versus the other two
      states could be performed with a sensitivity and specificity of about 95% while
      the more interesting task of distinguishing danger of suction from no suction
      reached a sensitivity and specificity of about 65% (leaving 25% of each class
      unclassified and 10% of each class incorrectly classified).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8572983
TI  - Development of a new apparatus to observe microcirculation chronically in
      continuous flow blood pump research.
AB  - To observe microcirculation chronically is an important key to the successful
      evaluation of the continuous flow blood pump. In this study, we succeeded in
      developing a new apparatus by which microcirculation could be observed
      chronically without a microscope in a conscious animal. The apparatus utilizes a
      charge coupled device (CCD). A thin living tissue, such as mesentery, is put
      directly on a highly integrated CCD and is lit up through the tissue with a light
      emitting diode (LED). The vascular nets in the tissue are projected onto the CCD
      like a contact photograph, which is then sent to a television screen and which
      can be used to analyze their motion and function. A 0.5-inch CCD having 250,000
      pixels was used in this study. The cover glass of the CCD was removed, and a
      fiber optic plate was fixed onto the surface of the CCD for the tissue to be able
      to contact with the apparatus surface without clearance. The CCD as well as the
      LED were molded with epoxy resin for electrical insulation. The apparatus was 35
      mm wide and 12 mm high with a micro stand for an LED, which can be easily
      implanted into an animal. The apparatus was implanted into a rabbit for 12 h. The
      configuration of arterioles and venules, tens of micrometers in diameter, and
      their motions in subcutaneous tissue could be observed.

PMID- 8572984
TI  - Fractal dimension analysis of the oscillated blood flow with a vibrating flow
      pump.
AB  - To analyze the hemodynamic parameters during circulation with oscillated blood
      flow, nonlinear mathematical analyzing techniques, including fractal theory, were
      utilized. Vibrating flow pumps (VFP) were implanted as a left heart bypass, and
      the ascending aorta was clamped to constitute the total left heart circulation
      with oscillated blood flow in acute animal experiments using 7 adult goats. Using
      nonlinear mathematical analyzing techniques, reconstructed attractors of the
      arterial blood pressure waveform in the phase space during natural circulation
      and oscillated circulation were analyzed. Using the Grassberger-Procaccia
      correlation dimension analyzing technique, fractal dimension analysis of the
      reconstructed attractor was performed. During VFP bypass, lower fractal
      dimensions of the reconstructed attractor were shown compared with those during
      natural heart circulation. The results suggest that lower dimensional chaotic
      dynamics contributed to the circulation with oscillated blood flow.

PMID- 8572985
TI  - Experimental use of a semipulsatile rotary blood pump for cardiopulmonary bypass.
AB  - We tested our valveless pulsatile rotary blood pump (CORA) extensively in
      animals, but only as a temporary implantable left ventricular assist device. To
      expand the scope of future clinical applications, we recently undertook
      experiments to assess the feasibility of our pump for use in a standard
      cardiopulmonary bypass circuit. We conducted 4 experiments in adult sheep (body
      weight, 40 kg): 2 with CORA and 2 with the BioMedicus pump (BP) for comparison.
      In all experiments, a currently used extracorporeal circuit with reservoir,
      filter, and membrane oxygenator (Sorin monolith) was installed, and open chest
      extracorporeal circulation (ECC) was performed for 6 h. Hemodynamic performance
      and hemolysis were evaluated. CORA provided semipulsatile systemic flow at a
      level comparable to that of the BP. Free plasma hemoglobin levels were slightly
      higher with CORA, but the decrease in platelet count was the same for both
      devices. There was no significant difference in the extent of blood trauma. We
      conclude that CORA could be successfully used for ECC with an oxygenator.
      Negative pressure can be prevented by our specially designed control system.

PMID- 8572986
TI  - A right ventricular hemopump restores right ventricular function with pulmonary
      artery banding.
AB  - We investigated the ability of the Hemopump to support the right ventricle during
      acute, partial, pulmonary artery obstruction. In 6 pigs, a 14 Fr size Hemopump
      was placed through the pulmonary artery into the right ventricle. Control
      measurements were made. A band around the pulmonary artery proximal to the
      outflow port of the Hemopump was tightened, and measurements were repeated with
      the Hemopump at minimum and then maximum speed. With banding, right ventricular
      stroke volume and output decreased (43 [SD, 7] to 28 [SD, 8] ml, p < 0.001; 4.9
      [SD, 0.8] to 3.7 [SD, 1.0] L/min, p < 0.01 respectively), but they were restored
      with the Hemopump (38 [SD, 5] ml and 4.5 [SD, 0.6] L/min; both p = NS vs
      control). Increases in right ventricular peak systolic (28 [SD, 10] to 42 [SD,
      17] mm Hg; p < 0.01) and end-diastolic pressure (2 [SD, 1] to 12 [SD, 6] mm Hg; p
      < 0.02) were reversed by the Hemopump (29 [SD, 8] and 4 [SD, 2] mm Hg; both p =
      NS vs control). Right ventricular pressure rate product almost doubled with
      banding (3,199 [SD, 1,252] to 5,962 [SD, 2,796] mm Hg; p < 0.01), but it
      decreased with the Hemopump (3,368 [SD, 767] mm Hg; p = NS vs control). With
      acute partial pulmonary artery banding, a right ventricular Hemopump restores
      output from and offloads the right ventricle.

PMID- 8572987
TI  - Mechanical unloading with a miniaturized axial flow pump (hemopump): an
      experimental study.
AB  - A family of miniaturized axial flow pumps has been developed, including the
      Hemopump, the 14-F, and the 21-F HP, which were especially designed for
      cardiological use. We designed an experimental set-up to study the unloading
      properties of these devices in a model of regional stunning in an anesthetized,
      open thorax preparation in sheep. Stunning was caused by 15-min occlusion of the
      diagonal branch of the left anterior descending coronary artery with subsequent
      90 min of reperfusion. Regional myocardial function was assessed by
      sonomicrometry. A control group was compared with 2 groups with either mechanical
      unloading during part of ischemia (Group 2) or the early phase of reperfusion
      (Group 3). In either unloading protocol, both Hemopumps were used. It was shown
      that recovery from asynchrony was significantly faster in Groups 2 and 3 if
      unloading was performed with the 21-F HP compared with control Group 1 and the
      groups using the 14-F HP (p > 0.05). Thus, mechanical unloading with the 21-F
      Hemopump enhances recovery from stunning whereas unloading with the 14-F HP has
      only minor effects on hemodynamics and no effects on recovery.

PMID- 8572988
TI  - Gas exchange efficiency of a membrane oxygenator with use of a vibrating flow
      pump.
AB  - We have developed a newly designed blood pump, named the vibrating flow pump
      (VFP), which can generate high frequency oscillated flow. The driving frequency
      is 10-50 Hz, and flow volume is linearly controlled electric power (current and
      voltage). The VFP was applied as the pump for extracorporeal circulation (ECC) in
      acute animal experiments. The gas exchange efficiency of the membrane oxygenator
      with the VFP and a roller pump (RP) was evaluated. Under general anesthesia with
      halothane, 7 adult goats underwent ECC; an inflow cannula was inserted into the
      right atrium, an outflow cannula was sutured to the descending thoratic aorta,
      and total ECC was performed with a flow of about 80 ml/min/kg. The ECC system
      with the VFP showed excellent gas exchange efficiency compared with that of the
      RP. The hemodynamics of ECC using the VFP were easily maintained within normal
      limits. These results suggest that the VFP is very useful as a pump for ECC;
      thus, a compact-sized ECC system may be achieved.

PMID- 8572989
TI  - Clinical situations and results of cardiopulmonary support by peripheral access
      for resuscitation and recovery.
AB  - Use of cardiopulmonary support (CPS) by peripheral access with a membrane
      oxygenator has made considerable progress as a result of the development of
      centrifugal pumps, percutaneous cannulation, and preheparinized circuits. We have
      used CPS for resuscitation in 3 cases, for recovery after cardiotomy in 6 cases
      (myocardial insufficiency, 4; pulmonary arterial hypertension, 1; respiratory
      insufficiency, 1), and after heart transplantation in 1 case. Of these 10
      patients, 3 died during CPS, 5 were successfully weaned, and 2 underwent heart
      transplantation. Use of CPS is expanding for emergency cardiac assistance.
      Installation is simple and rapid. It allows recovery of organs pending more
      invasive and costly techniques.

PMID- 8572990
TI  - Clinical experience with BioMedicus centrifugal ventricular support in 172
      patients.
AB  - One hundred and seventy-two patients at The Methodist Hospital in Houston, Texas,
      were placed on BioMedicus centrifugal ventricular support. One hundred thirty
      nine patients were male and 33 were female with a mean age of 59.7 years. Reasons
      for support were postcardiotomy cardiac failure (129 patients), cardiac allograft
      failure (17 patients), bridge to transplantation (10 patients), resuscitation (7
      patients), postpercutaneous transluminal coronary angioplasty emergent (2
      patients), and other (7 patients). Support was by left ventricular assist device
      in 108 patients, right ventricular assist device in 20 patients, and
      biventricular assist device in 44 patients. Eighty-four patients (48.8%) were
      weaned from the ventricular assist device, and 88 patients (51.2%) were not
      weaned. Thirty-four patients (20.0%) were discharged from the hospital.
      Complications included coagulopathy, renal insufficiency/failure, respiratory
      insufficiency/failure, neurological deficits, sepsis, arrhythmias, and device
      related complications. Overall causes of death were ventricular failure (55.1%),
      triage (13.0%), arrhythmias (9.4%), graft failure (5.9%), coagulopathy (4.3%),
      sepsis syndrome (2.9%), device-related (0.7%), and other (0.7%). BioMedicus
      centrifugal ventricular support can be implemented rapidly and easily. Device
      related complications are few (1.2%), and it is relatively inexpensive when
      compared with other ventricular assist systems. This series demonstrates that a
      substantial number of patients may benefit from temporary centrifugal ventricular
      support.

PMID- 8572991
TI  - Improving clinical outcome with centrifugal mechanical assist for postcardiotomy
      ventricular failure.
AB  - Between October 1986 and May 1994, 65 patients undergoing cardiac surgery
      required centrifugal mechanical assist devices to separate from cardiopulmonary
      bypass. This experience was arbitrarily divided into early (n = 33) and recent (n
      = 32) groups for the purpose of comparing trends in morbidity and mortality. The
      incidence of mechanical assist application decreased from 2.19% in the early
      group to 0.96% in the recent group (p < 0.0001). Ability to wean patients from
      centrifugal assist increased from 33% in the early group to 53% in the more
      recent group, and hospital survival increased from 15 to 28%. The median chest
      tube drainage during the first 24 h decreased from 3,245 ml to 1,535 ml, and the
      incidence of renal failure decreased from 39.4% and 18.8% in the more recent
      group. Clinically relevant improvement in patient outcome following application
      of centrifugal mechanical assist for postcardiotomy ventricular failure is being
      observed.

PMID- 8572992
TI  - Current strategy for severe heart failure with mechanical circulatory support.
AB  - In the last 10 years, 37 patients received assisted circulation or a ventricular
      assist device after open-heart operations at the Heart Institute of Japan. After
      cardiovascular surgery, 12 patients underwent venoarterial bypass (VAB), 13 had
      biventricular bypass (BVB), 8 had left ventricular bypass (LVB), and the
      remaining 4 received a left ventricular assist device (LVAD). Weaning and
      discharge rates of the patients by type of circulatory supports were 41.7 and
      25.0% with VAB, 69.3 and 46.2% with BVB, 87.5 and 37.5% with LVB, 75.0 and 50.0%
      with LVAD, and 44.4 and 11.1% with PCPS, respectively. Concerning complications
      of postcardiotomy circulatory support, hemorrhage and ventricular arrhythmia
      postcardiotomy circulatory support, hemorrhage, and ventricular arrhythmia
      (immature weaning) decreased with low-heparinized isolated left ventricular
      supports (i.e., LVB, LVAD). However, profound biventricular failure, infection,
      and multiple organ failure remain as possible complications with any type of
      assisted circulation. These results suggest that early application of circulatory
      support and appropriate selection of the mode of support and devices used are
      important for successful circulatory support.

PMID- 8572993
TI  - Initial clinical experience with the Baylor-Nikkiso centrifugal pump.
AB  - Recently, a newly developed centrifugal pump, the Baylor-Nikkiso pump, was
      approved for clinical use in the United States. This pump is the most compact
      centrifugal pump with a priming volume of only 25 ml. Although it is small, this
      pump can provide a flow of 4 L/min against a total pressure head of 300 mm Hg at
      3,000 rpm. In vitro and in vivo validation of the Baylor-Nikkiso pump has proved
      that this pump could effectively reduce blood trauma even under high total head
      pressure. In addition, 48-h durability tests with biventricular bypass using
      calves verified the reliability of shaft sealing and antithrombogenicity.
      Clinical trials of the Baylor-Nikkiso pumps have been initiated in our
      department. This pump provides flows of 60-70 ml/kg/min with stable hemodynamic
      conditions. No leakage of thrombus formation was observed. The results of the
      initial clinical experience of the Baylor-Nikkiso pump suggest that it is
      suitable for cardiopulmonary bypass surgery.

PMID- 8572994
TI  - Left atrial-aortic/femoral bypass with a centrifugal pump without systemic
      heparin during surgery on the descending aorta.
AB  - Active or passive bypass to support the distal circulation during cross-clamping
      of the descending thoracic aorta has been reported to decrease the incidence of
      paraparesis, to reduce left ventricle afterload, and to preserve distal organ
      perfusion. The aim of this study was to describe and to evaluate a perfusion
      technique for surgery on the descending aorta in humans. Nine patients underwent
      surgery on the descending thoracic aorta. The left atrium was cannulated using a
      Carmeda bioactive surface cannula. Distal cannulation sites were the left common
      femoral artery or the aorta below the involved segment. The cannulae were
      connected to a BioMedicus centrifugal pump via Carmeda bioactive surface tubings
      and pump heads. No systemic heparin was used. Cross-clamp time was 51 +/- 6 min,
      and the pump flow was 2.3 +/- 0.2 L/min. The mean arterial pressure in the upper
      body was 81 +/- 4 mm Hg and 68 +/- 5 mm Hg in the lower. Seven patients were
      discharged from hospital. Two patients with aortic rupture died; one died on the
      operating table, and the other, neurologically intact, died 4 days
      postoperatively due to multiorgan failure. No patients suffered spinal cord
      injury. It is concluded that active bypass without systemic heparin during cross
      clamping of the descending aorta is simple and safe.

PMID- 8572995
TI  - BioMedicus ventricular assistance for postcardiotomy heart failure: evaluation of
      univentricular assistance.
AB  - Clinical outcome and hemodynamic effects of unilateral mechanical ventricular
      support (UMVS) were evaluated in 19 patients with postcardiotomy heart failure
      refractory to conventional treatment. Adequate circulation with UMVS was
      maintained in about 75% of the patients. UMVS initiated circulatory stabilization
      in 5 of 6 patients with biventricular failure, in 2 of 3 patients with right
      ventricular failure, and in 7 of 10 patients with left ventricular failure. Eight
      (42%) patients were successfully weaned from UMVS and discharged from hospital.
      Six (32%) patients died despite a prolonged, stabilized circulation by UMVS. In 5
      (26%) patients, the UMVS could not secure stable circulation. Application of the
      left UMVS induced increases in cardiac output and systemic blood pressure and a
      decrease in left atrial pressure without changes in pre- and afterload of the
      right ventricle. It is concluded that application of UMVS may induce adequate
      circulation in patients with postcardiotomy heart failure refractory to treatment
      with inotropes and intraaortic counterpulsation. The outcome of UMVS in left,
      right, and biventricular failure is acceptable. Thus, this treatment may be
      recommended for patients with postcardiotomy heart failure.

PMID- 8572996
TI  - Who wins in medical lawsuits?

PMID- 8572997
TI  - Small particles in medicine.

PMID- 8572998
TI  - Function and metabolism of brain synaptosomes in chronic renal failure.
AB  - Patients with advanced renal failure have derangements in the function of their
      nervous system. The available clinical and experimental data indicate that the
      state of the secondary hyperparathyroidism of renal failure plays a major role in
      the genesis of the nervous system dysfunction. The excess parathyroid hormone
      (PTH) mediates its deleterious effect by causing an elevation in cytosolic
      calcium of brain cells. This report reviews the evidence leading to the
      conclusion that PTH is a major uremic toxin.

PMID- 8572999
TI  - Hemodialysis with cellulose membranes primes the neutrophil oxidative burst.
AB  - Hemodialysis with cellulose membranes causes a complement-mediated neutropenia.
      Changes in neutrophil function have also been reported; however, it is unclear if
      these changes indicate a direct effect of the membrane on neutrophils or if they
      are a consequence of the neutropenia. We tested the hypothesis that neutrophil
      oxidative burst activity is enhanced during dialysis with cellulose membranes.
      Resting and Staphylococcus aureus-stimulated H2O2 production were determined
      predialysis and in blood entering and leaving the dialyzer during the first 30
      min of dialysis and in blood leaving the membrane module in a single-pass on-line
      model of hemodialysis. Resting H2O2 production increased slightly but
      significantly during the first 30 min of dialysis. Transit of neutrophils through
      the dialyzer caused a marked increase in stimulated H2O2 production, indicating
      priming of the oxidative burst. However, priming was limited to the first 5 min
      of dialysis before the onset of neutropenia. In contrast, stimulation and priming
      of H2O2 production persisted throughout 30 min of single-pass on-line perfusion.
      These results indicate that cellulose membranes both stimulate and prime
      neutrophil oxidative burst activity but that these effects are partially obscured
      by neutropenia.

PMID- 8573000
TI  - Hantaan virus infection with acute renal failure.
AB  - We report on 10 patients with acute renal involvement in Hantaan virus infection
      observed at the Department of Nephrology, Faculty of Medicine, Skopje, Republic
      of Macedonia, during a period of 3 years (October 1987-July 1990). Eight patients
      were male and 2 were female, aged 37.5 +/- 4.8 years. The diagnosis of Hantaan
      virus infection was proven by an indirect immunofluorescent and ELISA test with a
      significant increase of the titer after a week to ranges from 1:512 to 1:2,048.
      Percutaneous renal biopsy was performed in 3 cases using standard procedures for
      optical and immunofluorescent microscopy. Fever, weakness, headache, conjunctival
      injection, hematuria, and lumbar pain were clinical features all patients had in
      common. Complete anuria was noted in 7 out of 10 and oliguria in the other 3 of
      the 10 cases with serum levels of creatinine 967 +/- 152.6 mumol/L. Other
      following laboratory findings were leukocytosis in 10 out of 10 patients, with
      neutrophylia, and reduction of serum sodium and potassium in 8 out of 10, and a
      decrease in serum complement C3 in 3 out of 10 patients. Percutaneous renal
      biopsy confirmed interstitionephritis in 2 out of 3 biopsied patients and acute
      diffuse proliferative glomerulonephritis in the third. Interstitial mononuclear
      infiltration with dominant T cells proven with monoclonal antisera (direct
      immunoperoxidase method) was present in all 3 cases. The outcome of the disease
      was good in 8 of the 10 patients with a development of polyuric phase and
      complete recovery of renal function later. One patient with interstitial lesions
      on biopsy developed chronic renal failure, and the other with a concomitant
      brucellosis died during the polyuric phase of the disease.

PMID- 8573001
TI  - Hemocompatibility in hemodialysis and erythropoietin therapy.
AB  - Two studies designed to investigate the effect of recombinant human
      erythropoietin (rHuEPO) treatment of anemia in chronic dialysis patients on
      hemocompatibility were conducted. Study 1, whose main aim was to establish
      whether treatment with rHuEPO enhances coagulation activation during dialysis,
      included 15 patients before rHuEPO therapy at a mean hematocrit (HCT) of 22.3%
      and then during therapy at a HCT of 29.3%. The plasma concentrations of the
      thrombin-antithrombin III complex were not higher during rHuEPO therapy than
      before it when performing hemodialysis with a Cuprophan membrane. No significant
      difference was demonstrated either in the values of activated clotting times
      (Hemochron), thrombocyte or white blood cell counts (Coulter S+II), or in plasma
      C5a concentrations (ELISA) established during dialysis sessions before and during
      rHuEPO therapy. In Study 2, which focused primarily on the question of whether or
      not rHuEPO therapy increases thrombocyte activation during hemodialysis, 8
      patients on chronic dialysis were examined both before therapy at a mean HCT
      value of 22.1% and during rHuEPO therapy at a HCT of 31.5%, invariably during
      dialysis with either a Cuprophan or polyacrylonitrile (AN69HF) membrane. The
      plasma concentrations of beta-thromboglobulin (ELISA) did not differ between the
      examinations made during rHuEPO and before rHuEPO therapy; however, statistically
      significant differences were found between dialysis sessions involving Cuprophan
      and AN69HF membranes. No significant difference between examination before and
      during rHuEPO was demonstrated in activated clotting time nor thrombocyte and
      white blood cell counts in this study either. The authors conclude that rHuEPO
      therapy does not enhance coagulation activation during hemodialysis, does not
      have an effect on thrombocyte activation, and does not influence complement
      activation and changes in white blood cell counts.

PMID- 8573002
TI  - Quantitative reticulocyte analysis may be of benefit in monitoring erythropoietin
      treatment in dialysis patients.
AB  - Reticulocyte responses to low-dose erythropoietin (EPO) were monitored using
      automated flow cytometric analysis. Sixteen adult dialysis patients were treated
      with 1,000 U of recombinant human EPO (rHuEPO), subcutaneously, thrice weekly
      (mean dose 15.7, SD 3.7 U/kg). The reticulocyte count (baseline 31.1, SD 19.1 x
      10(9)/L) increased in 14 patients in the first week, with a peak response
      occurring at Week 2 (mean 57.3, SD 26.5 x 10(9)/L, p < 0.01). There was a wide
      spectrum of response, the maximal absolute increment ranging from 6.8-69.7 x
      10(9)/L (maximal percentage increase 19-863%). Overall there was no relationship
      between the early increment in reticulocyte count and hemoglobin (Hb) response
      over the ensuing 4 months. Nine patients became transfusion independent (mean Hb
      increasing from 6.9, SD 0.8-9.2, SD 1.2 g/dl). Two patients had poor reticulocyte
      increments and no significant change in Hb. The remaining 5 patients responded
      partially with a brisk reticulocyte response and a marked reduction in
      transfusion dependency, but without a sustained increase in Hb. On investigation,
      all had gastrointestinal bleeding (melena in 1, commencing after initiation of
      treatment, positive fecal occult bloods in 4), whereas none of the other patients
      showed evidence of blood loss. It is notable that the erythron was sensitive to
      this modest dose of rHuEPO in the majority of patients as evidenced by the
      reticulocyte response. The results provide useful information in the management
      of patients on rHuEPO. A small or inapparent reticulocyte response suggests a
      confounding factor; a poor Hb response in the presence of active reticulocyte
      synthesis points to occult blood loss or hemolysis.

PMID- 8573003
TI  - Morbidity and mortality in hemodialysis: the role of schedules.
AB  - Hemodialysis is an efficient therapy for endstage renal failure. This treatment,
      however, must be used in an optimal fashion, i.e., with the best technology and
      the most adequate schedules. Unfortunately and especially for economic reasons,
      these basic therapeutic principles are often not respected. As a consequence,
      morbidity and mortality in maintenance hemodialysis patients have increased. This
      article underlines four points that could influence mortality in maintenance
      hemodialysis patients: nutrition, adequacy of hemodialysis, blood pressure
      control and treatment time.

PMID- 8573004
TI  - Analysis of the urea generation rate and the protein catabolic rate in
      hemodialyzed patients.
AB  - The urea generation rate (G) and the protein catabolic rate (PCR) have been
      investigated in two groups of hemodialyzed patients over a whole week cycle, one
      with zero residual renal function (Kr = 0) dialyzed thrice weekly and the other
      dialyzed twice weekly with nonzero residual renal function. The two-pool model of
      urea kinetics was used. No relationship between patients' age and the PCR was
      found, and also no difference in the PCR between males and females was seen. All
      patients with a PCR < 0.8 g/kg/day had a midweek predialysis plasma urea level
      well below 25 mmol/L, which clearly documents the value of a kinetic approach in
      early detection of patients at risk for malnutrition. In the thrice weekly
      dialyzed group, a statistically significant relationship was found between PCR
      and KT/V:PCR = 0.582 + 0.253 x KT/V, r = 0.374 with p < 0.05. In the twice weekly
      dialyzed group with nonzero Kr, contribution of the residual renal function had
      to be included into KT/V to reach a level of statistical significance of PCR =
      0.697 + 0.18 x KT/V, r = 0.481 with p < 0.05. With regard to values of Kr
      encountered in the investigated group (0-3.5 ml/min), its influence upon PCR is
      higher than a volumetrically equal increase in excretorial efficacy of the
      artificial kidney. The G in the thrice weekly dialyzed group was found to be
      dependent on the length of the interdialytic interval over which it was
      evaluated. Over the intervals Friday-Monday, Monday-Wednesday, and Wednesday
      Friday the following mean values of G were obtained: 0.155, 0.180, and 0.188
      mmol/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8573005
TI  - Nutritional treatment of hemodialysis and peritoneal dialysis patients.
AB  - The success of hemodialysis and peritoneal dialysis therapy is essentially
      dependent on adequate nutrition. Malnutrition represents one of the main factors
      in morbidity and mortality of dialysis patients. The main causes of malnutrition
      are insufficient energy intake, insufficient protein supply, loss of amino acids
      by dialysis, the uremic state of metabolism, catabolic stress of underlying
      diseases, and endocrinological disorders. For successful long-term chronic
      dialysis therapy, it is very important that patients be in an anabolic
      nutritional state when entering the dialysis program. In this paper, the
      nutritional needs of dialysis and peritoneal dialysis patients (fluid
      restriction, protein intake, energy supply, electrolyte balance, vitamin intake)
      are discussed to prevent the catabolic state.

PMID- 8573006
TI  - Influence of hemodialysis membranes on gene expression and plasma levels of
      interleukin-1 beta.
AB  - Plasma levels of interleukin-1 beta (IL-1 beta) were measured in 10 normal
      subjects, in 11 nondialyzed end-stage renal failure (ESRD) patients, and in 22
      hemodialysis (HD) patients. Of the HD patients, 7 were dialyzed with Cuprophan
      (CU), 7 with polymethylmethacrylate (PMMA), and 8 with polysulphone (PS)
      dialyzers. In normal controls, nondialyzed ESRD patients, and HD equipped with
      CU, PAMM, and PS dialyzers, plasma levels of IL-1 beta were 10.73 +/- 5.24 pg/ml,
      9.97 +/- 3.61 pg/ml, 13.17 +/- 4.04 pg/ml, 15.16 +/- 6.16 pg/ml, and 13.96 +/-
      5.47 pg/ml, respectively. There were no statistically significant differences
      among the groups (p > or = 0.05). In contrast, the gene expression of IL-1 beta
      for peripheral blood mononuclear cells (PBMC) by in situ hybridization showed
      differences among the groups. The gene for IL-1 beta for PBMC appears in HD
      equipped with different membranes, but not in cases of nondialyzed uremic
      patients and normal subjects. With computer imaging analysis, we carried out
      quantitative analysis of cells in in situ hybridization with an area of positive
      spots to an area of total cells. In HD with CU, PMMA, and PS, the results were
      10.64 +/- 1.07, 3.34 +/- 0.74, and 3.27 +/- 0.64%, respectively. The levels of IL
      1 beta gene expression in CU were higher than that in PMMA or PS. There were
      statistically significant differences (p < or = 0.001) between CU and PMMA or PS
      and no significant difference between the PMMA and PS (p > or = 0.05). We suggest
      measuring the gene expression of cytokines for PBMC and which may be better than
      measuring cytokine levels only for investigating the blood compatibility of
      dialyzers, which may help in understanding chronic complications of the dialysis
      procedure.

PMID- 8573007
TI  - New methods for the investigation of blood-biomaterial interaction.
AB  - Quantitative microscopy with integrated image processing is a useful tool for
      investigation of the interaction of blood components with biomaterials. We have
      developed new automated measuring devices suitable for simultaneously
      characterizing biological cells (size, shape, localization, migration,
      electrophoresis), synthetic particles (electrophoretic fingerprinting), and
      dialysis membranes (morphology, electric charge). These techniques are useful for
      the investigation of cell adherence on biomaterials, localization of cells in
      membrane filters (Chemotaxis), characterization of the protein adsorption on
      model systems, detection of cytokines (produced after lymphocyte-biomaterial
      contact), and estimation of morphological properties and charge distribution in
      dialysis membranes.

PMID- 8573008
TI  - Blood-contacting biomaterials: bioengineering viewpoints.
AB  - The investigation of blood-contacting biomaterials is an important challenge and
      is relevant for an improvement in the clinical application of biomaterials. With
      the purpose of improved clinical treatment, bioengineering viewpoints of blood
      contacting biomaterials cover the material options and selection, the utilization
      of materials, the development of materials with better properties, and processing
      characteristics, and the design of relevant evaluation procedures. The
      bioengineering objective remains that of achieving an enhanced understanding of
      the relationship between a biomaterial and the biological response.

PMID- 8573009
TI  - Evaluation of the antithrombogenicity of a new microdomain structured copolymer.
AB  - A new antithrombogenic material was studied, fluorine-acryl-styrene-urethane
      silicone (FASUS) copolymer, the theoretical basis of which attributed to its
      hydrophilic and hydrophobic microdomain structure. In this series of experiments,
      the blood compatibility of this copolymer was evaluated in vitro and ex vivo. For
      the in vitro evaluation, a whole blood clotting test and the microsphere column
      test were performed. For the ex vivo evaluation, two series of shunt tests in
      rabbits were performed, one was the arterioartery (A-A) shunt model, and the
      other was the arteriovenous (A-V) shunt model. The antithrombogenicity was
      assessed by measuring the shunt obstructive time in the A-A shunt experiment. The
      A-V shunt experiment was assessed by measuring the circulating platelet counts,
      platelet aggregability, activated partial thromboplastin time (APTT), and
      prothrombin time (PT). In the whole blood clotting test, FASUS revealed the
      significantly longer blood clotting time than that of the control glass tubings
      (19.7 +/- 1.0 versus 6.5 +/- 0.7 min, p < 0.001). In the microsphere column test,
      the coated group had a 30% reduction of the platelet number in the eluted blood
      in contrast with a marked decrease of 70% in the control group (p < 0.05). In the
      ex vivo A-A shunt experiment, the occlusion time for the FASUS-coated group was
      significantly longer than that of the control (109.7 +/- 17.3 versus 3.0 +/- 0.4
      min, p < 0.05). The A-V shunt experiment showed that the FASUS copolymer
      suppressed the decrease in platelet counts and tended to improve prolonged APTT
      compared with that of the control. Clinically, in 25 patients, we placed coated
      FASUS copolymer into the cannulas for use in percutaneous cardiopulmonary support
      (PCPS) procedures. There was no evidence of thrombus on the blood contacting
      surface and no thromboembolism in major organs clinically or upon postmortem
      examination. In summary, this new copolymer may be effective in preventing
      thrombus formation in vitro, ex vivo, and in clinical situations.

PMID- 8573010
TI  - Separation of the natural atria in experimental implantation of total artificial
      heart.
AB  - Atrial connections in a single-unit total artificial heart (TAH) may be difficult
      to make because of the rigidity of the device and the fixed position of the
      atrial inlets. We developed a technique to separate the natural atrial borders in
      an experimental implantation of a unitary TAH. In this technique, the interatrial
      groove was dissected to separate the posterior wall of the right atrium from the
      roof of the left atrium before cardiopulmonary bypass (CPB) was initiated. After
      initiation of CPB and cardiectomy, the atrial septum was separated completely,
      and the right atrial wall was reconstructed with glutaraldehyde-treated
      autopericardium. We believe that this simple adjunctive technique provides
      increased mobility of the atrial cuffs and allows for an easier connection of the
      unitary TAH.

PMID- 8573011
TI  - Development of an isolated perfusion circuit with double bypass using automatic
      blood pumps.
AB  - Isolated perfusion of the liver is a useful and promising therapeutic method for
      various hepatic diseases. However, conventional techniques using a roller pump
      require a large priming volume and cannot run at the low flow rate without
      complications. These disadvantages do not allow the use of conventional
      techniques in smaller pediatric patients. The authors solved these problems
      successfully for the first time by using unique sac-type air-driven automatic
      blood pumps with an oxygenator primed with a blood volume of 65 ml in the total
      circuit. The usefulness of these blood pumps for liver perfusion was evaluated in
      small animals weighing 3.5-6.0 kg. A hepatic perfusion circuit was established
      between the portal vein and the inferior vena cava. The blood pumps worked well
      without any trouble, and stable flow could be maintained. No hepatocellular
      damage or anaerobiosis of the liver was observed at a hepatic perfusion flow rate
      of 20 ml/min/kg. Isolated liver perfusion using these blood pumps can be applied
      in infants and young children.

PMID- 8573012
TI  - From the rotating drum to the pineapple-cancoil kidney: the unpublished history
      of the twin-coil.

PMID- 8573013
TI  - Ruptured globes following radial and hexagonal keratotomy surgery.
AB  - OBJECTIVE: To ascertain if cases of radial keratotomy wound rupture were
      occurring and whether the globes ruptured through the corneal incisions. DESIGN:
      Cases of traumatic ruptured globe after incisional corneal refractive surgery
      were collected from ophthalmologists and from peer-reviewed and other ophthalmic
      literature. RESULTS: Twenty-eight human eyes (eight previously unreported) are
      known to have ruptured through refractive corneal incisions in activities of
      daily living (n = 12), assault (n = 7), motor vehicle accidents (n = 5), and
      sports (n = 4). Two patients died of their injuries. Of the remaining 26 ruptured
      eyes, eight (31%) recovered 20/40 or better visual acuity. Six eyes (23%) were
      totally blinded, six (23%) were legally blinded, and six (23%) had best corrected
      visual acuity of 20/40 to 20/100 despite multiple surgical procedures.
      CONCLUSIONS: As radial keratotomy becomes more popular the pool of patients who
      may experience traumatic ruptured globe will grow. Every patient who has had
      radial keratotomy should be aware that the surgery has weakened the eye(s).

PMID- 8573014
TI  - Hydrogel intracorneal lenses in aphakic eyes.
AB  - BACKGROUND: The theoretical benefits of synthetic keratophakia over conventional
      corneal lamellar procedures are the elimination of donor concerns and superior
      refractive predictability. Additionally, synthetic material can be inspected for
      optical quality and power, and it can be sterilized. Furthermore, visual recovery
      should be more rapid since epithelium is not removed from the central part of the
      cornea and the need for keratocyte repopulation is eliminated. OBJECTIVE: To
      present results on patients who received an intracorneal implant (Kerato-Gel,
      Allergan Medical Optics, Irvine, Calif) that was made from lidofilcon A, a
      glucose-permeable hydrogel with an equilibrium water content of 68%. METHODS: The
      intracorneal implants were implanted in 35 adult patients for correction of
      aphakia. Inclusion criteria excluded patients with aphakia who were candidates
      for intraocular lenses. RESULTS: A total of 19 patients were followed up through
      2 years postoperatively. For 16 patients with 2-year postoperative refractive
      data, the average spherical equivalent was -0.63 +/- 2.07 diopters (D). At 2
      years, 88% of patients were within +/- 3.00 D of plano and 50% were within +/-
      1.00 D. the mean change in Snellen's line for corrected visual acuity was -3.25
      lines at 2 years for all patients and -2.0 lines for a subgroup of five patients
      who were free of vision-limiting preoperative disease. CONCLUSIONS: Results
      suggest that this intracorneal implant is well tolerated by the cornea and can
      provide predictable refractive results in patients with high-risk aphakia.
      Limitations of the procedure are uneven microkeratome resections, loss of best
      corrected visual acuity, and irregular astigmatism in some patients. Although
      these data show good evidence of biocompatibility of the implant material,
      technical surgical progress is needed to advance this procedure into clinical
      therapeutic practice.

PMID- 8573015
TI  - Normal respiratory chain function in patients with low-tension glaucoma.
AB  - OBJECTIVE: To test the hypothesis that low-tension glaucoma has a pathogenesis
      similar to Leber's hereditary optic neuropathy and results from a defect in the
      mitochondrial respiratory chain. METHODS: Mitochondrial fractions were prepared
      from skeletal muscle samples collected from eight subjects with low-tension
      glaucoma. Their oxidative metabolism was compared with that of age- and sex
      matched controls. Skeletal muscle DNA prepared from the subjects with glaucoma
      was also screened for the 3,460, 11,778, and 14,484 mitochondrial DNA mutations
      that are associated with Leber's hereditary optic neuropathy. RESULTS: No subject
      with low-tension glaucoma had a defect in respiratory chain activity or one of
      three mitochondrial DNA mutations that are commonly associated with Leber's
      hereditary optic neuropathy. CONCLUSION: Although these results do not exclude
      the possibility that low-tension glaucoma is caused by an organ-specific defect
      of mitochondrial function, we have excluded a systemic defect of the
      mitochondrial respiratory chain.

PMID- 8573016
TI  - Early retinal vessel development and iris vessel dilatation as factors in
      retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity (CRYO-ROP)
      Cooperative Group.
AB  - OBJECTIVE: To determine whether the extent of retinal vessel development present
      on early screening examinations for retinopathy of prematurity has prognostic
      value? DESIGN: The prospectively collected data from the Multicenter Trial of
      Cryotherapy for Retinopathy of Prematurity were used to compare the development
      of acute retinopathy of prematurity and long-term structural and visual outcomes
      for eyes with differing extents of retinal vessel development. PATIENT: Study
      patients had eyes with the following vessel development. In zone I eyes, vessels
      extended from the disc less than twice the distance from the disc to the macula.
      In zone II eyes, vessels extended beyond zone I but not to the nasal ora serrata.
      Transitional eyes had vessels partly in zone I and partly in zone II. RESULTS:
      The chance of developing threshold retinopathy of prematurity was inversely
      related to the early degree of vessel development: 54% for zone I eyes, 25% for
      transitional eyes, and 8% for zone II eyes. The presence of prominent iris
      vessels at 34 to 35 weeks of postmenstrual age was associated with increased risk
      for all three groups; zone I eyes almost always needed treatment (94%). The
      chance of having an unfavorable anatomic alteration of the posterior fundus, or
      poor vision at the ages of 1 year and 3 1/2 years, was also inversely related to
      the degree of early vessel development. Vessel development was an independently
      important factor even when birth weight, gestational age, and race were
      considered. CONCLUSIONS: The degree of early retinal vessel development is a
      significant predictor of outcome from retinopathy of prematurity. Iris vessel
      dilatation is an important indication for greater vigilance in following these
      infants.

PMID- 8573017
TI  - Vascular consequences of retinectomy.
AB  - OBJECTIVE: To define the vascular sequelae of retinectomy. DESIGN: Clinical and
      angiographic survey of patients who had undergone retinectomy procedures.
      PATIENTS: Twenty consecutive patients with ambulatory vision and attached
      posterior retina after retinectomy procedures underwent ophthalmic examination,
      including retinal biomicroscopy, indirect ophthalmoscopy with scleral
      indentation, and peripheral retinal fluorescein angiography. RESULTS: Ten eyes
      (50%) showed anterior retinal neovascularization (NV), with vessels derived from
      the ciliary body or posterior retina. Neovascularization occurred in residual
      anterior retina adjacent to the retinectomy, in detached anterior retina
      demarcated by laser in quadrants not involved by retinectomy, and in fibrinous
      membranes extending anterior to the retinectomy edge. This was associated with
      postoperative vitreous hemorrhages in two patients. Iris NV and inferior
      iridectomy occlusion were strongly associated with retinal NV (Fisher's exact
      test, P < .005). No patient had neovascular glaucoma or optic disc NV during a
      median follow-up of 250 days (range, 121 to 465). CONCLUSIONS: Retinectomy may
      have profound secondary effects on ocular vascular circulation, resulting in
      retinal NV in association with iris NV, occlusion of inferior iridectomies, and
      vitreous hemorrhage. Complete intraoperative removal of residual anterior retina
      to the ora serrata in quadrants involved by retinectomy, combined with
      prophylactic retinal laser treatment from the vitreous base to the ora in the
      remaining quadrants, is recommended to prevent the development of retinal NV and
      its associated complications.

PMID- 8573018
TI  - Sources of variability of topometric data with a scanning laser ophthalmoscope.
AB  - OBJECTIVE: To determine in a two-part study whether misalignment between the
      patient and the laser scanner is a major source of variability with the
      Heidelberg Retina Tomograph (Heidelberg [Germany] Engineering). METHODS: Three
      topographic images of the right optic nerve were acquired with the Heidelberg
      Retina Tomograph in eight patients with glaucoma. The correlations between
      average cup volume, variability of cup volume estimates, and direction of imaging
      were evaluated. Furthermore, the correlations between average rim volume,
      variability of rim volume estimates, and direction of imaging were evaluated.
      Next, the optic nerve cup volume and rim volume estimates of a rabbit's left eye
      were compared between three series of five topographic images acquired from three
      slightly different directions. RESULTS: Average cup volume, variability of cup
      volume estimates, and variability in the direction of imaging correlated
      significantly among the patients with glaucoma (multiple R2 = .95; P < .001).
      Average rim volume, variability of rim volume estimates, variability in the
      direction of imaging, and variability in the mean height of the contour line also
      correlated significantly (multiple R2 = .88; P = .03). In the rabbit eye, the cup
      volume and the rim volume differed significantly among the three image series
      (analysis of variance, P < .001 and P = .04, respectively). CONCLUSION:
      Misalignment between the patient and the laser scanner may account for
      significant variability with the Heidelberg Retina Tomograph.

PMID- 8573019
TI  - Imaging congenital optic disc pits and associated maculopathy using optical
      coherence tomography.
AB  - OBJECTIVE: To elucidate the anatomy of congenital optic disc pits with and
      without maculopathy using optical coherence tomography. SETTING: All patient were
      examined, photographed, and scanned at the New York Eye and Ear Infirmary.
      PATIENTS: Ten eyes of eight consecutive patients with congenital optic disc pits
      were studied. Three eyes had associated serous macular detachment (group 1), four
      had evidence of resolved detachment (group 2), and three had no clinical macular
      pathologic lesion (group 3). METHODS: Optical coherence tomography, a new,
      noninvasive, noncontact, imaging technology capable of producing cross-sectional
      images of the retina in vivo with high resolution ( < 17 microns) was used to
      obtain multiple cross-sectional images of the pit, peripapillary retina, and
      macula. Ophthalmologic examination and standard fundus photography were performed
      on all eyes. Fluorescein angiography was performed in eyes that had associated
      macular detachment. RESULTS: Communication between a schisis cavity or subretinal
      space and the optic nerve pit was imaged in all eyes in group 1. No such
      communication could be identified in groups 2 and 3. Cystic degeneration and
      schisis were imaged in the peripapillary retina, macula, or both in all eyes of
      groups 1 and 2 and in one patient in group 3. A direct communication between the
      subretinal space and vitreous cavity could not be identified in any eye.
      CONCLUSIONS: Schisis formation plays an integral role in the development of
      serous retinal detachment in the presence of congenital optic disc pits. Our
      findings are consistent with the theory that the optic disc pit acts as a conduit
      for fluid flow between the schisis cavity or subretinal space and the
      subarachnoid space.

PMID- 8573020
TI  - The relative afferent pupillary defect and a novel method of fusion recovery with
      the Worth 4-dot test.
AB  - OBJECTIVE: To examine the relation of the relative afferent pupillary defect and
      commonly used clinical tests of visual cortex binocular cell activity, namely,
      fusion and stereopsis. METHODS: Sixty-seven subjects with neuro-ophthalmologic
      disorders underwent measurement of relative afferent pupillary defect and
      assessment of binocular sensory status by fusion on the Worth 4-dot test and
      stereopsis on the Titmus stereo test. Recovery of fusion on the Worth 4-dot test
      and improvement of stereopsis were tested by placing increasing neutral density
      filters in front of the eye that did not have the afferent pupillary defect.
      RESULTS: Recovery of fusion on the Worth 4-dot test occurred with use of neutral
      density filters (Worth 4-dot neutralization test). No improvement of stereopsis
      was observed. A significant positive association was identified between the
      measured afferent pupillary defect and the measured log filter required for
      fusion (r = .83, P < .001 by the Spearman rank correlation coefficient). In no
      case was a relative afferent pupillary defect observed when fusion without use of
      neutral density filters was present at baseline. For subjects with relative
      afferent pupillary defects, the measurements of the Worth 4-dot neutralization
      test were equal before and after pupillary dilation. CONCLUSIONS: The relative
      afferent pupillary defect is a dynamic process that results from an imbalance of
      brightness sensitivity between the two eyes. Altering the latency ("timing") and
      amplitude of the light stimuli by use of neutral density filters can restore
      fusion on the Worth 4-dot neutralization test but does not alter stereopsis. The
      Worth 4-dot neutralization test may be a useful adjunct in the assessment of
      visual dysfunction.

PMID- 8573021
TI  - Is alignment within 8 prism diopters of orthotropia a successful outcome for
      infantile esotropia surgery?
AB  - OBJECTIVE: To determine if there is better long-term motor alignment or sensory
      outcome 5 years after surgery for infantile esotropia for patients who exhibit
      any of three categories of alignment 6 months after surgery: orthotropia, up to 8
      prism diopters (delta) of esotropia, or up to 8 delta of exotropia. DESIGN: A 15
      year prospective study with 5-year outcome determination was conducted in
      surgically treated esotropic infants. RESULTS: Of 118 patients in the study
      group, 24 had orthotropia, 84 had up to 8 delta of esotropia, and 10 had up to 8
      delta of exotropia 6 months after surgery. The patients who were orthotropic 6
      months after surgery were more likely to show good alignment and better
      binocularity 5 years after surgery than were patients with small-angle esotropia
      or small-angle exotropia. Patients who were esotropic 6 months after surgery were
      more likely to have good alignment and binocularity 5 years after surgery than
      were patients who were exotropic 6 months after surgery. CONCLUSION: Small-angle
      esotropia, small-angle exotropia, and orthotropia are not equally desirable
      outcomes after surgery for infantile esotropia. Orthotropia is a decidedly better
      outcome than a small-angle esotropia, which is preferable to a small-angle
      exotropia.

PMID- 8573022
TI  - Hydration effects on corneal topography.
AB  - OBJECTIVE: To evaluate the effect of corneal thickness changes on the central and
      paracentral corneal topography in de-epithelialized eye-bank eyes at various
      stages of hydration. METHODS: Corneal topography of 12 eye-bank eyes was measured
      with a videokeratoscope at the following four stages of hydration: prethinning
      (mean pachymetry, 0.88 mm), postthinning (0.55 mm), after 15 minutes of
      rehydration (0.60 mm), and after 30 minutes of rehydration (0.64 mm). RESULTS:
      Corneal thickness changes were significant between each stage of hydration (P <
      .05 by repeated-measures analysis of variance). No net astigmatic shifts were
      observed between any stage of hydration (P = .45). From prethinning to
      postthinning, dehydration produced average central corneal steepening of 0.44
      diopters (P < .001), and average paracentral steepening of 0.89 D (P < .001).
      Significant changes in corneal power were not measured during normal rehydration
      until 30 minutes posthydration, when the central cornea had flattened an average
      of 0.3 D from normal thickness (postthinning) levels (P < .05). CONCLUSIONS:
      Substantive thinning of corneal tissue caused statistically significant but
      clinically minimal ( < 1 D) central and paracentral steepening, but smaller
      corneal hydration changes that can occur during experimental and surgical
      procedures had little effect on corneal topography.

PMID- 8573023
TI  - Photodynamic therapy of pigmented choroidal melanomas using a liposomal
      preparation of benzoporphyrin derivative.
AB  - OBJECTIVE: To evaluate the effectiveness of photodynamic therapy of pigmented
      choroidal melanoma using a liposomal preparation of benzoporphyrin derivative
      monoacid (BPD), verteporfin. DESIGN: Pigmented choroidal melanomas were
      established in 25 New Zealand albino rabbit eyes. The animals were treated with
      daily injections of cyclosporine, and tumor growth was monitored with funduscopic
      examination and ultrasonography. Fifteen minutes after intravenous injection of
      BPD (2 mg/kg), the tumors were irradiated at 692 nm through an argon-pumped dye
      laser with the delivered fluence ranging between 40 and 150 J/cm2. Control
      animals were treated with light only, photosensitizer only, or observation only.
      Tumor growth was monitored by indirect ophthalmoscopy, fundus photography,
      fluorescein angiography, and ultrasonography. Histologic examination was
      performed. RESULTS: Eighteen tumor-bearing rabbits were treated with light and
      BPD; 16 were followed up for 1 month, and two were killed immediately for
      histologic examination. Tumors regressed in all eyes treated with 60 J/cm2 or
      more. With fluence of 40 J/cm2, tumor regrowth was observed in one animal within
      10 days of treatment. In the three control groups, all animals showed continuous
      tumor growth. Histologic examination of the eyes treated with photosensitizer and
      light immediately after treatment showed prominent vascular occlusion throughout
      the full thickness of the tumor. One month after treatment, tumor necrosis and
      infiltration of mononuclear cells and pigment-laden macrophages were the
      predominant findings. CONCLUSIONS: Photodynamic therapy with BPD may have a role
      in the treatment of pigmented choroidal melanomas.

PMID- 8573025
TI  - New concepts of regulation of retinal vessel tone.
AB  - OBJECTIVE: To review the mechanisms of local regulation of the vascular tone of
      the retinal and choroidal circulations. DESIGN: Literature review. RESULTS: The
      vascular endothelial cell may produce nitric oxide, endothelins, prostaglandins,
      and renin-angiotension products in response to chemical stimuli such as
      acetylcholine and bradykinin, to changes in blood pressure and vessel wall
      stress, to changes in local oxygen levels, and to other local stimuli. These
      substances are among the most potent vasoconstrictors and vasodilators known.
      Preliminary investigations suggest a potential role for these substances in
      endothelial autoregulation of the retinal and choroidal vasculatures. CONCLUSION:
      Hormonal products of the vascular endothelium may provide the final common
      pathway for vessel autoregulation in response to varying physiologic stress in
      many vascular beds, including the retina and choroid. Pharmacologic modulation of
      this process may provide treatment modalities for diseases such as hypertensive
      and diabetic retinopathies.

PMID- 8573024
TI  - Linkage of autosomal dominant radial drusen (malattia leventinese) to chromosome
      2p16-21.
AB  - OBJECTIVE: To identify the chromosomal location of the gene involved in the
      pathogenesis of autosomal dominant radial drusen (malattia leventinese).
      PATIENTS: Eighty-six members of four families affected with radial drusen; one
      family of American origin and three families of Swiss origin. METHODS: Family
      members were clinically examined for the presence of radial drusen. Affected
      patients and potentially informative spouses were genotyped with short tandem
      repeat polymorphisms distributed across the autosomal genome. The clinical and
      genotypic data were subjected to linkage analysis. RESULTS: Fifty-six patients
      were found to be clinically affected. Significant linkage was observed between
      the disease phenotype and markers known to lie on the short arm of chromosome 2.
      The maximum two-point lod score (Zmax) observed for all four families combined
      was 10.5 and was obtained with marker D2S378. Multipoint analysis yielded a Zmax
      of 12, centered on marker D2S378. The lod-1 confidence interval was 8 cM, while
      the disease interval defined by observed recombinants was 14 cM. CONCLUSIONS: The
      gene responsible for autosomal dominant radial drusen has been mapped to the
      short arm of chromosome 2. This is an important step toward actually isolating
      the disease-causing gene. In addition, this information can be used to evaluate
      other familial drusen phenotypes such as Doyne's macular dystrophy for a possible
      allelic relationship.

PMID- 8573026
TI  - Open-angle glaucoma and blood groups. The Barbados Eye Study.
AB  - OBJECTIVE: To evaluate the association of open-angle glaucoma (OAG) with ABO, Rh
      and Duffy blood groups in the population-based Barbados Eye Study. DESIGN: Case
      control study. SETTING AND PARTICIPANTS: A subset of black Barbados Eye Study
      participants, which included 199 OAG cases and 1063 controls. DATA COLLECTION:
      ABO, Rh and Duffy blood groups were determined as part of a comprehensive study
      visit, which included assessment for OAG through perimetry, fundus photography,
      and ophthalmologic examination. OUTCOME MEASURES: Comparison of blood groups
      between OAG cases and nonOAG controls, expressed as odds ratio and 95% confidence
      intervals. RESULTS: Associations were found with the Duffy Fya+ group, which is
      more frequent in white than black populations. In Mantel-Haenszel analyses, OAG
      was positively associated with Duffy Fya+ in men (odds ratio, 2.67; confidence
      interval, 1.52 to 4.69) and in persons with intraocular pressure more than 21 mm
      Hg (odds ratio, 3.32; confidence interval, 1.49 to 7.38). Logistic regression
      analyses confirmed these findings (interaction of Duffy Fya+ and male gender, P =
      .01; interaction of Duffy Fya+ and intraocular pressure, P = .04). No
      associations between OAG and the ABO or Rh blood groups were seen. CONCLUSIONS:
      The associations with Duffy Fya+, which had not been reported previously in a
      black population, support the involvement of genetic factors in OAG. However, the
      lack of association between OAG and blood group markers of African ancestry is
      inconsistent with a genetic explanation for the differences in OAG prevalence
      between blacks and whites. Our findings suggest gene-environment interactions in
      OAG, to be explored by further studies of OAG and Fy markers by racial group and
      gender.

PMID- 8573027
TI  - Sight-threatening complications after radial keratotomy.

PMID- 8573028
TI  - The current use of botulinum toxin therapy in strabismus.

PMID- 8573029
TI  - Aggressive conjunctival squamous cell carcinoma in three young Africans.
AB  - Polymerase chain reaction was used to test for the presence of human
      papillomavirus in conjunctival squamous cell carcinomas from three young Africans
      with aggressive disease. Two of these patients had the acquired immunodeficiency
      syndrome. Test results for human papillomavirus were negative [corrected] in all
      three cases.

PMID- 8573030
TI  - Periorbital infantile myofibromatosis.
AB  - An 11-day-old boy was found to have a lesion of the left lower eyelid and medial
      canthus. The mass was present at birth and subsequently enlarged, and was
      subtotally excised when the child was 2 months old. Histopathologic examination
      disclosed a fascicular to slightly nodular pattern of predominantly spindle
      shaped cells. Special stains demonstrated fibroblastic and smooth-muscle features
      in individual cells, and infantile myofibromatosis was diagnosed. Sixteen months
      postoperatively, no evidence of recurrence was noted. We believe this is the
      first case of infantile myofibromatosis of the solitary type involving the ocular
      adnexa of a neonate to be reported in the English literature. Infantile
      myofibromatosis of the solitary type appears to have an excellent prognosis and
      may be treated with conservative resection if the tumor infiltrates important
      adnexal structures.

PMID- 8573031
TI  - Anatomic considerations in the implantation of the Ahmed glaucoma valve.

PMID- 8573032
TI  - Successful feeder vessel laser treatment of recurrent neovascularization
      following subfoveal surgery.

PMID- 8573033
TI  - Frostbite of the eyelids following inappropriate application of ice compresses.

PMID- 8573034
TI  - Multiple endocrine neoplasia type IIB.

PMID- 8573035
TI  - The protective effect of the tilted disc syndrome in diabetic retinopathy.

PMID- 8573036
TI  - Risk factors for open-angle glaucoma: the Barbados Eye Study.

PMID- 8573037
TI  - Dietary fat and age-related maculopathy.

PMID- 8573038
TI  - The sterile organisation.

PMID- 8573039
TI  - "Freedom's just another word": aboriginal youth and mental health.
AB  - OBJECTIVE: The aim of the study was to review the available material on
      Aboriginal youth mental health, exploring certain contemporary issues. METHOD:
      The review covers the psychiatric and social science literature, focusing on the
      recent period of major social change. RESULTS: The available material is severely
      limited, particular deficiencies being normal child development, the impact of
      social change and its consequences for the construction of Aboriginal identity.
      CONCLUSION: There is a need for more work in this area and for psychiatric
      engagement at a political level.

PMID- 8573040
TI  - The clinical boundaries of posttraumatic stress disorder.
AB  - Three sets of clinical boundaries exist for posttraumatic stress disorder (PTSD),
      as for all concepts of psychiatric disorder. The first involves the border with
      normal psychology in general, and with the normal psychology of stress response
      in particular. This boundary can be surveyed from a number of vantage points and
      the maps which result will not necessarily correspond. The second boundary issue
      involves internal boundaries between psychiatric disorders, specifically between
      PTSD and other concepts of disorder. The high level of comorbidity documented in
      PTSD has ensured that this aspect of boundary setting is particularly
      contentious. The third set of boundaries is concerned with subtyping within the
      global construct of PTSD. The validity and extent of subtyping would be based on
      the degree to which phenomenological differences exist in relation to PTSD
      syndromes occurring in the wake of certain types of traumatic events. Such
      clinical subtyping might however need to be buttressed by external validity
      indicators such as differential treatment responses or outcome. A final boundary
      issue of major significance to therapists involves the need to place oneself
      unambiguously on the side of the trauma survivor in the struggle to resolve the
      traumatic experiences. The pivotal position of PTSD in the psychopathological
      arena is discussed.

PMID- 8573041
TI  - Workforce deployment: reconciling demands and resources.
AB  - OBJECTIVE: The purpose of the study was to review the information in a
      Consultancy prepared for the National Mental Health Policy which suggested that
      half of the people with serious mental illnesses were untreated, while persons
      with "mental problems" were being overserviced by the specialist mental health
      services. The fate of the large group of persons with mental disorders of mid
      range severity was not addressed. METHOD: Epidemiological data was reconciled
      with the service patterns of the clinical workforce and the extent of the unmet
      need estimated. RESULTS: It was estimated that 25-30% of the Australian
      population meet criteria for a mental disorder in any year, yet less than one
      third will receive treatment. Of those that are treated, three quarters will
      receive their treatment from general practitioners and the remaining quarter will
      be treated by either the public mental health services, the addition services, or
      private psychiatrists. The problem is that less than one half of those with
      serious mental disorders and only two thirds of those with chronic and disabling
      disorders appear to be being treated by anyone. Even if there were no slippage of
      services away from these serious and chronic groups of patients, there would
      still be a workforce shortfall, especially in rural and remote areas.
      CONCLUSIONS: Strategies to remedy this shortfall that involve psychiatrists,
      clinical psychologists and general practitioners are noted, and the need for a
      National Mental Health Survey to provide accurate data is stressed.

PMID- 8573042
TI  - The relationship between social factors and frequent use of psychiatric services.
AB  - The purpose of the study was to develop a comprehensive demographic, diagnostic
      and social profile of patients who are heavy service users of hospital and
      community based services within the South Australian Mental Health Services
      (SAMHS). This paper concentrates on the relationship of social issues to heavy
      service use. The 50 heaviest users of public adult acute psychiatric services in
      a defined catchment area of Adelaide were identified. Data were obtained
      retrospectively from the case notes over a 3 year study period. All patients'
      primary therapists were interviewed, as were 35 of the patients. These structured
      interviews included a variety of psychosocial rating scales investigating
      disability and social networks. The 50 patients studied were found to be
      seriously disabled by chronic psychiatric illness, with substance abuse often
      complicating their management and their ability to live successfully in the
      community. The study confirms the emergence in the literature of a valid global
      profile of the heavy service user patient, and indicates that social factors are
      strongly related to heavy service use.

PMID- 8573043
TI  - Borderline personality disorder: a challenge for mental health services.
AB  - OBJECTIVE: This study had two main aims: to determine the stability over time of
      the diagnosis borderline personality disorder (BPD) in a psychiatric hospital
      population; and to assess the quality and effectiveness of treatment offered
      within state mental health service. METHOD: The case notes of 47 psychiatric
      hospital patients followed up for 3 years after the index admission were
      analysed. RESULTS: The mean number of previous psychiatric hospital admissions
      was 9.0, and at least 74% of the sample had further admissions (mean 3.7) during
      the 3 year follow-up. Comorbidity with schizophrenia and schizoaffective disorder
      was rare, and was only 13% with major depression. Longitudinal stability of
      diagnosis was very high. CONCLUSIONS: The study firmly supported BPD as a valid
      diagnosis. Its treatment within the state mental health system was generally
      haphazard and ineffective. Post-discharge plans were implemented for only 3
      subjects. Current moves toward community psychiatric treatment represent a unique
      opportunity for improving treatment of BPD by using existing resources more
      effectively.

PMID- 8573044
TI  - The loss of the sense of reality in incest and child sexual abuse: a
      psychoanalytic perspective.
AB  - This article takes a psychoanalytic perspective on incest and child sexual abuse.
      It concentrates on what could be called "the loss of the sense of reality" that
      is experienced by the victim of incest. The position in which a child of five is
      placed when she is sexually abused by her father is considered; this is followed
      by detailed material from the analysis of a woman who had an incestuous
      relationship with her brother. Transference and counter-transference difficulties
      that arise in work with abused patients are explored. A theoretical explanation
      of the damaging effects of an incestuous relationship is outlined.

PMID- 8573045
TI  - Consultation-liaison psychiatry in general medical units.
AB  - The activities of a consultation-liaison psychiatry service to general medical
      units in a university affiliated suburban teaching hospital are described, with a
      report from the MICRO-CARES clinical database on 165 consecutive referrals over a
      12 month period. The referral rate was 4.2% of admissions. The data confirm the
      association of psychiatric referral and prolonged length of hospital stay (mean
      of 18 days for referred patients, 9 days for non-referred patients). The most
      common reasons for referral were depression, suicide risk evaluation, organic
      brain syndrome and suspected psychological component to illness. The most common
      psychiatric diagnoses were Mood Disorders (55%), Organic Mental Disorders (35%),
      Adjustment Disorders (19%), Somatoform and other Somatic Disorders (16%) and
      Personality Disorders (15%). Although 67% of patients received at least one
      confirmed diagnosis, 39% of all diagnoses remained "differential", or
      unconfirmed, at discharge. Concordance with drug recommendations was 97% and with
      non-drug recommendations 95%. Two groups of patients were prominent among the
      referrals: the young self-poisoning patient, and the older patient living alone.
      The issues involved in providing a liaison psychiatry service to general medical
      units with these characteristics are described.

PMID- 8573046
TI  - Fluoxetine treatment of depressed patients with HIV infection.
AB  - OBJECTIVE: The aim of this paper is to describe the outcome of fluoxetine
      treatment of depressed patients with HIV infection. METHOD: An open study was
      made of 20 patients with varying stages of HIV infection treated for depression
      with fluoxetine. RESULTS: 15 of 20 patients improved with fluoxetine treatment;
      the drug was generally well tolerated, with no significant drug-drug
      interactions. CONCLUSIONS: Fluoxetine appears to be effective for the treatment
      of depression in patients with HIV infection.

PMID- 8573047
TI  - Disruptions in childhood parental care as risk factors for major depression in
      adult women.
AB  - OBJECTIVE: The aim of this study was to examine the influence of different types
      of disruptions in childhood parental care before the age of 15 years as risk
      factors for major depression in women aged 18 to 44 years. The types of
      disruptions studied were parental death, parental separation or divorce, other
      types of loss (i.e. adoption, foster-care, etc.), and prolonged separation from
      both parents. Potential confounding factors were also examined. METHOD: The data
      were obtained from a community probability sample. Caseness was determined by the
      use of the Diagnostic Interview Schedule (DIS) and both the current (one month)
      and lifetime prevalence periods were considered. Logistic regression was used to
      model the influence of each factor, singly and adjusted for the influence of
      other factors, on the risk for major depression. RESULTS: It was found that in
      this population 17% had experienced some type of parental loss (parental death
      4%, separations/divorce 10% and other types of loss 3%) and 11% had experienced
      prolonged separation from both parents. Parental loss was significantly
      associated with lifetime depression, but this effect was no longer significant
      when adjusted for other factors. However, prolonged separation from both parents
      was associated with an increased risk of current and lifetime depressive episodes
      of approximately three to fourfold, even when the risk was adjusted for other
      factors. CONCLUSIONS: The results of this study suggest that prolonged separation
      from both parents has a stronger association with current or lifetime depression
      in women than do parental death, separation/divorce and other types of loss.
      Prolonged separation may be a marker for other risk factors and may not be a risk
      factor on its own.

PMID- 8573048
TI  - Seasonality of mania: a Tasmanian study.
AB  - OBJECTIVE: The aim of the study was to examine the seasonal incidence of mania in
      a new Southern Hemisphere location. METHOD: Using the Tasmanian psychiatric
      database, monthly admission rates were compared with expected admission rates for
      mania for the period 1983 to 1989. ICD-9 criteria for mania single episode
      (296.0) and mania recurrent episodes (296.1) were used, excluding individuals
      with a bipolar disorder (296.4 to 296.89). RESULTS: One thousand three hundred
      and twenty-eight persons were admitted during this period. There was a
      significant monthly variation with admissions occurring most commonly in the
      summer, but this was not consistent during the seven year period. CONCLUSIONS:
      There was a statistically significant but inconstant summer excess. The
      inconstancy of the finding suggests that the phenomenon is not a simple
      consequence of light duration, and closer examination of these inconsistencies
      may lead to further elucidation of the phenomenon.

PMID- 8573049
TI  - A community study of preschool behaviour disorder in New Zealand.
AB  - A two stage epidemiological study of 320 children aged between 2.5 and 5 years of
      age, from eight randomly selected preschool centres, was performed in order (1)
      to test the psychometrics of the Behaviour Check List (BCL), a parent report
      instrument for preschool children, (2) to estimate the prevalence, and (3) to
      describe the correlates of preschool behaviour disorder. After the initial
      screening using the BCL, the Hyperactivity Scale (HAS) and the Internalising
      Disorder Scale (IDS), parents were interviewed using the Behaviour Screening
      Questionnaire (BSQ); the children were examined using the Rutter and Graham's
      interview. Data was also collected on family functioning, maternal mental health,
      social adversity, development, physical health and perinatal history. The BCL was
      found to be a reliable and valid screening measure. A cut off point of 8+ was
      established for New Zealand preschoolers; this is lower than that in the UK
      sample, illustrating the importance of retesting the instruments in a different
      culture. The prevalence rate of behaviour problems based on clinical diagnosis
      was 22.5%. Results of logistic regression analysis showed that poor family
      functioning, poor maternal mental health and parental separation were associated
      significantly with behaviour disorder. This study emphasises the need to identify
      preschool behaviour disorder and associated risk factors to enable an early
      intervention.

PMID- 8573050
TI  - Working with survivors of torture and trauma: the Victorian Foundation for
      Survivors of Torture in perspective.
AB  - The health and welfare needs of refugee survivors of torture and trauma have in
      recent years belatedly found a prominent place on the policy agendas of Federal
      and State Governments. The development of a statewide service to meet these needs
      provides an opportunity to illustrate some of the general issues in developing a
      model specialist community health service, as well as the specific and complex
      elements involved in the care and resettlement of refugee survivors of torture
      and trauma. The early experience of the Victorian Foundation for Survivors of
      Torture is described and some descriptive data presented. Unresolved issues are
      highlighted, particularly the difficulty in providing skilled psychotherapeutic
      assistance to relatively large numbers of traumatised refugees.

PMID- 8573051
TI  - Suicidal ideation and behaviours among university students in Australia.
AB  - OBJECTIVE: The aim of the study was to investigate the prevalence and demographic
      correlates of suicidal ideation and behaviours among university students in
      Australia and the utilisation of mental health services by this population.
      METHOD: Suicidal ideation and behaviours and demographic variables were assessed
      in a population of 1,678 undergraduate students by use of a modified Suicide
      Ideation Scale (SIS) and questionnaire. RESULTS: Sixty two percent of students
      surveyed showed some suicidal ideation and 6.6% reported one or more suicide
      attempts. Over half of the group who reported suicide attempts did not use any
      type of mental health services. Suicidal ideation was found to be highly
      correlated with previous use of mental health services. In examining the
      relationship between suicidal ideation (SI) and demographic variables, SI was not
      significantly different for gender or parental marital status but was related to
      living arrangements, racial groups, religious affiliation and father's education.
      CONCLUSIONS: The results suggest that a higher proportion of students reported
      suicidal ideation and behaviours than that documented in related studies
      undertaken in the USA. While these findings draw attention to a higher level of
      suicidal ideation in students who utilise mental health assistance, more than
      half of those who reported suicide attempts did not use any kind of mental health
      service. The study has particular implications for detecting and assisting young
      people with a high suicide risk within the university environment.

PMID- 8573052
TI  - Effects of newspaper stories on the incidence of suicide in Australia: a research
      note.
AB  - This study investigates the impact of newspaper stories on the incidence of
      suicide in Australia. The effects of suicide stories appearing in two major
      metropolitan newspapers between 1.1.1981 and 31.12.1990 were examined. The
      findings show that the daily average suicide rate in Australia increases
      significantly after the publication and publicity of suicide stories in the
      Australian media; the rise tends to be primarily due to the increase in male
      suicide and not female suicide. Some plausible explanations of this finding are
      advanced.

PMID- 8573053
TI  - Fitting the treatment to the patient: recent advances in the practice of
      electroconvulsive therapy.
AB  - Traditionally it has been thought that a grand mal seizure is both necessary and
      sufficient for the maximum efficacy of ECT. Recent important research, however,
      has demonstrated that both the electrical dosage above the seizure threshold,
      i.e. the suprathreshold dosage, and the electrode placement (unilateral or
      bilateral) determine the efficacy of this treatment, as well as the degree of
      cognitive impairment. This article reviews the development of these significant
      concepts and suggests specific practical recommendations for incorporating these
      into contemporary ECT practice.

PMID- 8573054
TI  - The Life Skills Profile: a study of its psychometric properties.
AB  - Two hundred patients with severe mental illness of mixed type were assessed by
      treating mental health professionals a total of 730 times with the Life Skills
      Profile (LSP). Confirmatory factor analyses broadly confirmed the existence of
      the Self-care and Non-turbulence subscales. Internal consistencies were generally
      good but inter-rater reliabilities were of only marginal acceptability. The fit
      of the data to the five subscales can be improved by reassigning two items. The
      Communication subscale had the poorest psychometric properties. Certain LSP scale
      scores were found to vary with how well and how long the rater had known the
      patient. Validity, which was assessed by relating LSP scores to locus of care
      (i.e. community or hospital), Brief Psychiatric Rating Scale (BPRS) ratings and
      Resource Associated Functional Level Scale (RAFLS) ratings, was good. An
      alternative scoring system yielded rather clearer meaning for some of the
      subscales.

PMID- 8573055
TI  - How do research psychiatrists rate? Views of neuroscientists.
AB  - OBJECTIVE: The aim of the paper is to define views of neuroscientists about
      research psychiatrists that might be restricting collaborative research. METHOD:
      A questionnaire was distributed to all members of the Australian Neuroscience
      Society. Forty-nine questionnaires were returned, and both quantitative and
      qualitative analyses undertaken. RESULTS: Neuroscientists rated research
      psychiatrists as "poor scientists" in having limited scientific training, being
      loose methodologists and in tending to cut corners, but also viewed research
      psychiatrists as addressing domains that generate harder research questions.
      Several factors inhibiting and promoting collaboration between neuroscientists
      and research psychiatrists were elicited. CONCLUSIONS: If collaborative links
      involving neuroscientists and research psychiatrists are to be enhanced, research
      psychiatrists will need to address and redress views about perceived limitations
      of their scientific competence.

PMID- 8573056
TI  - Munchausen syndrome by proxy abuse: a foundation for adult Munchausen syndrome.
AB  - Symptoms fabricated by the mother, and abnormal maternal pressurising of medical
      staff, resulted in misinterpretation of sweat test results and a diagnosis of
      cystic fibrosis in a two year old child. Her mother refused to accept later
      medical evidence which irrefutably showed this diagnosis to be wrong. The child
      was extensively investigated and for most of her childhood was treated for
      pancreatic malabsorption. She progressed from an innocent child victim of
      Munchausen Syndrome by Proxy abuse to an accomplice in her mother's deception,
      and finally to adult Munchausen Syndrome behaviour. Munchausen Syndrome by Proxy
      abuse may programme a child into developing adult Munchausen Syndrome.

PMID- 8573057
TI  - Self-amputation of the ear: three men amputate four ears within five months.
AB  - Four instances are presented of self-amputation of the pinna of the external ear
      carried out by three right-handed, white males between January 1993 and May 1993.
      The common characteristics of these subjects--two men with personality disorder
      and one with schizophrenia--are discussed and compared with other examples of
      self-mutilation involving the face and ears, including that of van Gogh. A survey
      of Australian and New Zealand prisons was conducted to determine the frequency of
      this form of self-mutilation within the last five years, and yielded only one
      other case. Connections exist between the amputees supporting the notion that
      self-mutilation is "contagious"; the relevance of this to issues of management is
      considered.

PMID- 8573058
TI  - Move from a syndrome-based schema?

PMID- 8573059
TI  - False memory syndrome.

PMID- 8573060
TI  - Suicidality and the use of serotonin reuptake inhibitors.

PMID- 8573061
TI  - SPECT imaging in psychiatry.

PMID- 8573062
TI  - Lithium carbonate-gluten intolerance.

PMID- 8573063
TI  - Exacerbation of extrapyramidal symptoms with paroxetine.

PMID- 8573064
TI  - Psychotropic drugs.

PMID- 8573066
TI  - A cytosolic sperm factor triggers calcium oscillations in rat hepatocytes.
AB  - Previously it has been shown that injecting a cytosolic sperm protein factor into
      mammalian eggs induces sustained repetitive transients of cytosolic free Ca2+
      ([Ca2+]i), or [Ca2+]i oscillations [Swann (1990) Development 110, 1295-1302].
      These sperm-factor (SF)-induced [Ca2+]i oscillations are similar to those seen at
      fertilization. Here we demonstrate that injecting the same cytosolic extracts of
      mammalian sperm into single rat hepatocytes induces a series of [Ca2+]i
      oscillations, as measured by aequorin luminescence. SF injection into hepatocytes
      induced [Ca2+]i oscillations that were of longer duration, lower frequency and
      greater amplitude than those seen with the Ins (1,4,5)P3-generating agonist
      phenylephrine. The SF-induced [Ca2+]i responses appeared to be due to internal
      release of Ca2+, since transients could occur in Ca(2+)-free media. Addition of
      the phorbol ester phorbol 12,13-dibutyrate (PDBu) at low concentrations did not
      inhibit the SF-induced [Ca2+]i oscillations; high concentrations of PDBu led to a
      sustained increase in [Ca2+]i concentrations. These data demonstrate that sperm
      contain a protein factor capable of inducing a characteristic series of [Ca2+]i
      oscillations in a somatic cell, the hepatocyte. Along with previous observations
      in dorsal root ganglion neurons, the data suggest a widespread efficacy of the
      factor in triggering Ca2+ oscillations.

PMID- 8573067
TI  - Relationship of human liver dihydrodiol dehydrogenases to hepatic bile-acid
      binding protein and an oxidoreductase of human colon cells.
AB  - We previously isolated three monomeric dihydrodiol dehydrogenases, DD1, DD2 and
      DD4, from human liver, and cloned a cDNA (C9) thought to encode DD2, which is
      identical with those for human bile-acid-binding protein and an oxidoreductase of
      human colon carcinoma HT29 cells. In the present study we have provided evidence
      that the C9 cDNA clone encodes DD1, not DD2. A recombinant enzyme expressed from
      the cDNA in a bacterial system was purified, and its catalytic properties, bile
      acid-binding ability and primary sequence were compared with those of the hepatic
      dihydrodiol dehydrogenases. The results show that DD1 encoded by C9 possesses
      prostaglandin F synthase activity but low affinity for lithocholic acid, whereas
      DD2, showing differences of six amino acid residues from the DD1 sequence,
      exhibited high-affinity binding for the bile acid. Refined relationship between
      dihydrodiol dehydrogenases and their related proteins of human tissues is
      proposed.

PMID- 8573068
TI  - Microsomal formation of S-nitrosoglutathione from organic nitrites: possible role
      of membrane-bound glutathione transferase.
AB  - The formation of S-nitrosoglutathione (GSNO) from amyl nitrite and n-butyl
      nitrite was studied in rat liver microsomes, employing N-ethylmaleimide (MalNEt)
      as an activator and indomethacin as an inhibitor of microsomal glutathione S
      transferase (GST). Rates were compared with GST activity measured with 1-chloro
      2,4-dinitrobenzene (CDNB) as a substrate. MalNEt stimulated GST activity and the
      formation of GSNO from amyl nitrite and n-butyl nitrite about 10-fold. Increasing
      concentrations of indomethacin inhibited both reactions in parallel. N-Acetyl-L
      cysteine but not L-cysteine could substitute for GSH. It is concluded that rat
      liver microsomal GST catalyses the formation of GSNO from amyl nitrite and n
      butyl nitrite. The activity of the MalNEt-stimulated microsomal GST is calculated
      to be about 17 units/mg of enzyme with the alkyl nitrites and about 16 units/mg
      of enzyme with CDNB as a substrate, assuming that 3% of microsomal protein is
      GST. These rates are comparable with those obtained for cytosolic GSTs. Thus
      microsomal GST may play a significant role in the metabolism of alkyl nitrites in
      biological membranes.

PMID- 8573069
TI  - Cloning, structure and mRNA expression of human Cctg, which encodes the
      chaperonin subunit CCT gamma.
AB  - We describe the cloning, DNA sequence analysis and mRNA expression analysis of
      human Cctg (HsCctg), a gene that encodes the gamma-subunit of the eukaryotic
      cytosolic 'chaperonin-containing TCP-1' (CCT). Partial clones representing the 3'
      region of HsCctg cDNA were isolated from a human kidney cDNA library, and the
      missing 5' region was amplified directly from human kidney cDNA. The Cctg mRNA
      transcript is expressed in numerous human and mouse tissues and, like Tcp-1/Ccta,
      Cctg mRNA is expressed at higher levels in mouse testis when compared with kidney
      and brain. Southern-blot analysis has also revealed the Cctg gene to be highly
      conserved in mouse, rat, sheep and frog. The 1901 bp HsCctg cDNA has a coding
      region of 1635 bp and encodes a predicted 60 kDa protein (544 amino acids). The
      predicted HsCCT gamma amino acid sequence shares a high degree of sequence
      similarity with gamma-subunits from the mouse Mus musculus (98% similarity), the
      yeast Saccharomyces cerevisiae (75% similarity) and the protozoan Tetrahymena
      pyriformis (76% similarity) as well as with other members of the TF55/TCP-1
      family, such as human TCP-1/CCT alpha (55% similarity) and TCP-20/CCT zeta (54%
      similarity). HsCCT gamma also shares conserved domains previously identified in
      the TF55/TCP-1 family of chaperonins and more distantly related chaperonins such
      as GroEL and Hsp60.

PMID- 8573065
TI  - Cellular consequences of thrombin-receptor activation.

PMID- 8573070
TI  - Blocking intracellular degradation of the erythropoietin and asialoglycoprotein
      receptors by calpain inhibitors does not result in the same increase in the
      levels of their membrane and secreted forms.
AB  - The erythropoietin receptor (EPO-R), a type 1 membrane glycoprotein, is degraded
      mainly in the lysosomes or endosomes, whereas the asialoglycoprotein receptor
      (ASGP-R) H2a subunit, a type 2 membrane glycoprotein, is degraded exclusively in
      the endoplasmic reticulum. The present study describes compounds that inhibit the
      intracellular degradation of these receptors in an efficient manner. However, the
      levels of cell-surface expression and secretion of their soluble exoplasmic
      domains were not enhanced to the same extent. The calpain inhibitors N-acetyl
      leucyl-leucyl-norleucinal (ALLN) and N-acetyl-leucyl-leucyl-methional (ALLM)
      inhibited EPO-R degradation profoundly. After 3 h of chase using Ba/F3 cells and
      NIH 3T3 fibroblasts expressing the EPO-R, virtually all of the receptor molecules
      were degraded, whereas 80% of the pulse-labelled receptor remained intact in the
      presence of the inhibitor. EPO-R cell-surface expression was elevated 1.5-fold
      after 1 h of incubation with ALLN. In the absence of protein synthesis, ALLN
      caused the accumulation of non-degraded EPO-R molecules in endosomes and
      lysosomes, as determined by double immunofluorescence labelling of NIH 3T3 cells
      expressing EPO-Rs. In Ba/F3 cells expressing a soluble EPO-R, ALLN treatment
      increased secretion of the soluble exoplasmic domain of the EPO-R 2-5-fold.
      Similarly, in NIH 3T3 cells singly transfected with the ASGP-R H2a subunit cDNA,
      ALLN inhibited degradation of the ASGP-R H2a subunit precursor, as well as the
      degradation of the 35 kDa proteolytic fragment corresponding to the receptor
      ectodomain, by 3-6-fold. However, accumulation of secreted proteolytic fragment
      in the medium was augmented in the presence of ALLN by only 1.75-fold. In cells
      expressing the G78R mutant of the ASGP-R H2a subunit, which is not cleaved to the
      35 kDa fragment [Yuk and Lodish (1993) J. Cell Biol. 123, 1735-1749], degradation
      of the precursor was inhibited. Overall, our data suggest the involvement of
      cysteine proteinases located in the endoplasmic reticulum, as well as in post
      Golgi compartments, in degradation of the EPO-R and the ASGP-R H2a subunit. The
      much lower effect of the inhibitory compounds on cell-surface and secreted forms
      of the EPO-R and ASGP-R H2a subunit illustrates the complexity and the tight
      regulation of the cellular localization and stability of membrane proteins.

PMID- 8573071
TI  - The phospholipase C/protein kinase C pathway is involved in cathepsin G-induced
      human platelet activation: comparison with thrombin.
AB  - Cathepsin G, an enzyme released by stimulated polymorphonuclear neutrophils, and
      thrombin are two human proteinases which potently trigger platelet activation.
      Unlike thrombin, the mechanisms by which cathepsin G initiates platelet
      activation have yet to be elucidated. The involvement of the phospholipase C
      (PLC)/protein kinase C (PKC) pathway in cathepsin G-induced activation was
      investigated and compared with stimulation by thrombin. Exposure of 5
      [14C]hydroxytryptamine-labelled platelets to cathepsin G, in the presence of
      acetylsalicylic acid and phosphocreatine/creatine kinase, induced platelet
      aggregation and degranulation in a concentration-dependent manner (0.1-3.0
      microM). Time-course studies (0-180 s) comparing equivalent concentrations of
      cathepsin G (3 microM) and thrombin (0.5 unit/ml) resulted in very similar
      transient hydrolysis of phosphatidylinositol 4,5-bisphosphate and steady
      accumulation of phosphatidic acid. In addition cathepsin G, like thrombin,
      initiated the production of inositol phosphates. The neutrophil-derived
      proteinase also induced phosphorylation of both the myosin light chain and
      pleckstrin, a substrate for PKC, to levels similar to those observed in platelets
      challenged with thrombin. Inhibition of PKC by GF 109203X, a specific inhibitor,
      suppressed platelet aggregation and degranulation to the same extent for both
      proteinases. Using fura 2-loaded platelets, the rise in the cytosolic free Ca2+
      concentration induced by cathepsin G was shown to result, as for thrombin, from
      both mobilization of internal stores and Ca2+ entry across the plasma membrane.
      These findings provide evidence that cathepsin G stimulates the PLC/PKC pathway
      as potently as does thrombin, independently of thromboxane A2 formation and ADP
      release, and that this pathway is required for platelet functional responses.

PMID- 8573072
TI  - Phosphorylation of recombinant human phenylalanine hydroxylase: effect on
      catalytic activity, substrate activation and protection against non-specific
      cleavage of the fusion protein by restriction protease.
AB  - The phosphorylation of human phenylalanine hydroxylase by cyclic AMP-dependent
      protein kinase was studied using recombinant enzyme expressed as a fusion protein
      in the pMAL system of Escherichia coli. Using the target sequence of the
      restriction protease enterokinase (Asp4-Lys) as the linker peptide, 100% full
      length human phenylalanine hydroxylase was obtained on protease cleavage. The
      fusion protein and human phenylalanine hydroxylase were both phosphorylated at
      Ser-16 with a stoichiometry of 1 mol of Pi/mol of subunit. The rate of
      phosphorylation of human phenylalanine hydroxylase was inhibited about 40% by the
      cofactor tetrahydrobiopterin, and this inhibition was completely prevented by the
      simultaneous presence of L-phenylalanine (i.e. at turnover conditions).
      Phosphorylated enzyme revealed a 1.6-fold higher specific activity than the non
      phosphorylated enzyme form, and it also required a lower concentration of L-Phe
      for substrate activation. Pre-incubation with L-Phe increased the specific
      activity of phenylalanine hydroxylase 2- to 4-fold, L-Phe acting with positive
      cooperativity. Thus, the basic catalytic and regulatory properties of recombinant
      human phenylalanine hydroxylase, as well as those observed for the enzyme as a
      fusion protein, are similar to those previously reported for the rat liver
      enzyme. When the target sequence of the restriction protease factor Xa (Ile-Glu
      Gly-Arg) was used as the linker between maltose-binding protein and human
      phenylalanine hydroxylase, cleavage of the fusion protein gave a mixture of full
      length hydroxylase and a truncated form of the enzyme lacking the 13 N-terminal
      residues. Interestingly, phosphorylation of the fusion protein, before exposure
      to factor Xa, almost completely protected against secondary cleavage by this
      restriction protease at Arg-13 of phenylalanine hydroxylase.

PMID- 8573073
TI  - Evidence for a covalent intermediate in the S-adenosyl-L-methionine-dependent
      transmethylation reaction catalysed by sirohaem synthase.
AB  - CysG, also known as uroporphyrinogen III methylase and sirohaem synthase (CysG;
      EC 2.1.1.107), is a multifunctional enzyme that is able to transform
      uroporphyrinogen III into sirohaem via two S-adenosyl-L-methionine (AdoMet)
      dependent transmethylations, an NAD(+)-dependent dehydrogenation and a
      ferrochelation. The apparent tight binding of AdoMet to this multifunctional
      enzyme is investigated. The use of a rapid AdoMet binding assay demonstrates that
      CysG becomes labelled with both [methyl-3H]AdoMet and [carboxyl-14C]AdoMet.
      Further experiments show that the CysG-AdoMet complex is subsequently able to
      methylate uroporphyrinogen III. CysG remains associated with the labelled
      constituents of the AdoMet even after denaturation with urea and SDS/PAGE,
      suggesting that the AdoMet has become covalently linked to the protein. A rapid
      examination of some of the other transmethylases involved in corrin biosynthesis
      reveals that they bind the AdoMet in a similar fashion. A multistep
      transmethylation mechanism is proposed to explain the observed results.

PMID- 8573074
TI  - Proteases of germinating winged-bean (Psophocarpus tetragonolobus) seeds:
      purification and characterization of an acidic protease.
AB  - Two major classes of protease are shown to occur in germinating winged-bean
      (Psophocarpus tetragonolobus) seeds, by assaying extracts at pH 8.0 and pH 5.1
      with [14C]gelatin as substrate. At pH 8.0, the activity profile of the enzyme
      shows a steady rise throughout the period of germination, whereas the activity at
      the acidic pH is very low up to day 5 and then increases sharply reaching a peak
      on day 11, followed by an equally sharp decline. The winged-bean acidic protease
      (WbAP) has been purified to apparent homogeneity, as attested by a single protein
      band on both PAGE and SDS/PAGE. WbAP is a monomeric enzyme with a molecular mass
      of 35 kDa and a pH optimum of 6.0. It is a thiol protease that does not belong to
      the papain family and it has tightly bound Ca2+ as shown by 45Ca(2+)-exchange
      studies. Besides gelatin and casein, it hydrolyses a 29 kDa winged-bean protein,
      indicating a prospective physiological role for it in storage-protein
      mobilization. Immunoblot analysis shows that it occurs only in the seeds and
      sprouting tubers of this plant and also that it is synthesized in developing
      seeds just before desiccation. It appears that the newly synthesized enzyme is
      inactive, and activation takes place around day 6 of germination. However,
      neither the mechanism of activation nor the signal that triggers it is clearly
      understood.

PMID- 8573075
TI  - Mucins in airway secretions from healthy and chronic bronchitic subjects.
AB  - Little is known about whether the properties of respiratory mucins are altered as
      a result of airway irritation, but histochemical studies of respiratory tract
      secretory cells show a more 'acidic' staining pattern after exposure to tobacco
      smoke. Furthermore it has been suggested that proteoglycans are the major
      glycoconjugates in 'normal' respiratory secretions, whereas mucins predominate in
      sputum. To investigate these observations further, mucins from secretions
      collected from the tracheal surface of healthy non-smoking 'normal' subjects and
      sputum from patients with chronic bronchitis were compared. All samples contained
      one major mucin population after density-gradient centrifugation, and a small
      amount of 'denser' mucin was present in some chronic bronchitic and one of the
      'normal' samples. Proteoglycans were not a major component of 'normal'
      secretions. The major mucin population from chronic bronchitic samples had
      molecular masses between 10 and 30 MDa and behaved as random coils in solution.
      Whole mucins from 'normal' individuals and chronic bronchitic patients were
      excluded from Sepharose CL-2B, whereas reduced subunits were included.
      Proteolysis of subunits yielded two populations of high-molecular-mass
      glycopeptides differing in size, suggesting the presence of two different tandem
      repeat regions in the mucins. Finally, mucins from patients with chronic
      bronchitis are less, rather than more, acidic than those from 'normal'
      individuals. Mucins from bronchitic sputum and 'normal' secretions are thus
      similar in their macromolecular properties, but differ slightly in charge
      density.

PMID- 8573076
TI  - Induction, not associated with host-cell re-activation of damaged plasmid DNA, of
      damaged-DNA-recognition proteins by retinoic acid and dibutyryl cyclic AMP in
      mammalian cells.
AB  - Our previous studies [Chao (1992) Biochem. J. 282, 203-207; C.C.-K. Chao,
      unpublished work] has suggested a correlation between the levels of constitutive
      UV-damaged-DNA-recognitionproteins (UVDRP) and cellular DNA repair in different
      cell types. In the present study, UVDRP were induced in F9 and NIH3T3 cells by
      0.1 microM retinoic acid (RA) and 1 mM dibutyryl cyclic AMP (dbcAMP), which is
      sufficient to induce differentiation in murine F9 stem cells. The induction of
      UVDRP in F9 and NIH3T3 cells was optimized after 6 and 2 days incubation with
      RA/dbcAMP respectively. Since NIH3T3 cells were not induced to differentiate by
      RA/dbcAMP, the upregulation of the UVDRP in mammalian cells would thus seem not
      to be mediated directly by differentiation. Using a plasmid re-activation assay
      to estimate DNA repair, we did not find a correlation between DNA repair and
      UVDRP in RA/dbcAMP-treated cells. The results suggest that UVDRP may have a
      function other than, or in addition to, its role in DNA repair.

PMID- 8573077
TI  - Molecular mechanism for catalysis by a new zinc-enzyme, dopachrome tautomerase.
AB  - Dopachrome tautomerase (DCT; EC 5.3.3.12) catalyses the conversion of L
      dopachrome into 5,6-dihydroxyindole-2-carboxylic acid in the mammalian
      eumelanogenic biosynthetic pathway. This enzyme, also named TRP2, belongs to a
      family of three metalloenzymes termed the tyrosinase-related proteins (TRPs). It
      is well known that tyrosinase has copper in its active site. However, the nature
      of the metal ion in the active site of DCT is under discussion. Whereas
      theoretical predictions based on similarity between the protein sequences of the
      TRPs suggest the presence of copper, the different inhibition pattern of DCT with
      some metal chelators compared with that of tyrosinase suggests that the nature of
      the metal ion could differ. Direct estimations of the metal content in purified
      DCT preparations show the presence of around 1.5 Zn atoms/molecule and the
      absence of copper. Apoenzyme preparation by treatment of DCT with cyanide or o
      phenanthroline followed by reconstitution experiments of tautomerase activity in
      the presence of different ions confirmed that the metal cofactor for the DCT
      active site is zinc. Our results are consistent with Zn2+ chelation by the highly
      conserved histidine residues homologous to the histidines at the classical copper
      binding sites in tyrosinase. This finding accounts for the reaction catalysed by
      DCT, i.e. a tautomerization, versus the copper-mediated oxidations catalysed by
      tyrosinase. Based on the predicted tetrahedrical coordination of the zinc ions in
      the enzyme active site, a molecular mechanism for the catalysis of L-dopachrome
      tautomerization is proposed. From the present data, the existence of additional
      ligands for metal ions other than zinc in the DCT molecule, such as the proposed
      cysteine iron-binding sites, cannot be completely ruled out. However, if such
      sites exist, they could be subsidiary binding sites, whose function would be
      likely to stabilize the protein.

PMID- 8573078
TI  - Antigenicity and conformational analysis of the Zn(2+)-binding sites of two
      Zn(2+)-metalloproteases: Leishmania gp63 and mammalian endopeptidase-24.11.
AB  - The antigenic properties of the Zn(2+)-binding region of two Zn(2+)
      metalloproteases, Leishmania surface protease gp63 and mammalian endopeptidase
      24.11 (E-24.11), possessing in their active site the characteristic amino acid
      sequence HEXXH, were investigated by using oligoclonal antibodies raised against
      two synthetic peptides, V1VTHEMAHALG11 (pepgp63) and V1IGHEITHGFD11 (pepE-24.11),
      containing the respective Zn(2+)-binding sites of the cognate protein. The
      affinity-purified antibodies, tested on synthetic peptides modelled from the
      active sites of ten different Zn(2+)-metalloproteases, showed high selectivity
      for their respective peptides. However, cross-reactivity was revealed when the
      antibodies were tested against the gp63 and E-24.11 molecules. A panel of
      synthetic peptide analogues and peptides of various size was synthesized and used
      for the fine antigenic characterization of pepgp63 and pepE-24.11. The shortest
      peptides capable of significant antibody binding were the pentapeptides V1VTHE5
      and E5ITHG9 for pepgp63 and pepE-24.11 respectively. His4 and Glu5 were found to
      be indispensable for anti-pepgp63 binding to pepgp63, whereas in the case of pepE
      24.11, Glu5 and His8 were found to be critical. The conformational
      characteristics of the two peptides correlate well with the observed differences
      in their antigenicity. 1H-NMR studies showed that pepgp63 adopts a folded
      structure whereas pepE-24.11 takes up a rather flexible conformation. Moreover,
      the antigenically critical His4 of pepgp63 contributes to the structural
      stabilization of the peptide. Similarly, the antigenically critical His8 of pepE
      24.11 is involved in partial structural stabilization of its C-terminal region.
      The generated antibodies may be useful tools for identifying and classifying
      proteins possessing similar Zn(2+)-binding motifs and/or environments.

PMID- 8573079
TI  - Molecular mechanisms of activated protein C resistance. Properties of factor V
      isolated from an individual with homozygosity for the Arg506 to Gln mutation in
      the factor V gene.
AB  - Resistance to activated protein C (APC), which is the most prevalent pathogenetic
      risk factor of thrombosis, is linked to a single point-mutation in the factor V
      (FV) gene, which predicts replacement of Arg (R) at position 506 with a Gln (Q).
      This mutation modifies one of three APC-cleavage sites in the heavy chain of
      activated FV (FVa), suggesting that mutated FVa (FVa:Q506) is at least partially
      resistant to APC-mediated degradation. To elucidate the molecular mechanisms of
      APC-resistance and to investigate the functional properties of FV in APC
      resistance, FV:Q506 was purified from an individual with homozygosity for the Arg
      to Gln mutation. Intact and activated FV:Q506 were demonstrated to convey APC
      resistance to FV-deficient plasma. Thrombin- or factor Xa-activated FV:Q506 were
      found to be approx. 10-fold less sensitive to APC-mediated degradation than
      normal FVa, at both high and low phospholipid concentrations. The degradation
      pattern observed on Western blotting suggested that FVa:Q506 was not cleaved at
      position 506. However, it was slowly cleaved at Arg306, which explains the
      partial APC sensitivity of FVa:Q506. FV is initially activated during clotting
      and then rapidly inactivated in a process which depends on the integrity of the
      protein C anticoagulant system. During clotting of APC-resistant plasma, FV:Q506
      was activated in a normal fashion, but then only partially inactivated. In
      conclusion, the reduced sensitivity of FVa:Q506 to APC-mediated degradation is
      the molecular basis for the life-long hypercoagulable state which constitutes a
      risk factor for thrombosis in APC-resistant individuals.

PMID- 8573080
TI  - Human ficolin: cDNA cloning, demonstration of peripheral blood leucocytes as the
      major site of synthesis and assignment of the gene to chromosome 9.
AB  - Pig ficolins and a number of other proteins contain sequences that are homologous
      to the C-terminal halves of fibrinogen beta- and gamma-chains. To clone the cDNA
      for human ficolin, two degenerate oligonucleotide primers were synthesized, based
      on two stretches of protein sequence that were highly conserved among those
      proteins, and used for PCR with cDNA from a human uterus lambda gt11 library as a
      template. A PCR product with a predicted size of 300 bp was obtained and this was
      used to screen a uterus cDNA library. Of the positive clones isolated, two (U1
      and U2), containing inserts of 1.7 and 1.1 kb respectively, were found to encode
      human ficolin. The cDNA-derived amino acid sequence of human ficolin has approx.
      75% identity with, and a similar domain organization to, the two pig ficolin
      sequences, which are characterized by the presence of a leader peptide, a short N
      terminal segment followed by a collagen-like region and then by a C-terminal
      fibrinogen-like domain. The 1.1 kb insert of clone U2 was used in Northern-blot
      analysis, and a very strong signal for a 1.4 kb mRNA species was detected in mRNA
      from human peripheral blood leucocytes. This showed that, despite the initial
      characterization of pig ficolin as a putative receptor on uterine cells for
      transforming growth factor beta 1, blood leucocytes are probably the major site
      of human ficolin synthesis. Much weaker signals of the same size were also
      detected in spleen, lung and thymus and may be due to the presence of tissue
      macrophages or trapped blood in these tissues. An mRNA species of approx. 1.3 kb
      in human liver also weakly hybridized to the U2 probe, indicating the presence of
      a sequence that was distinct from, but related to, ficolin. The gene for human
      ficolin has been mapped to chromosome 9.

PMID- 8573082
TI  - The effect of intracellular pH on long-chain fatty acid uptake in 3T3-L1
      adipocytes: evidence that uptake involves the passive diffusion of protonated
      long-chain fatty acids across the plasma membrane.
AB  - To understand the mechanism of long-chain fatty acid permeation of the plasma
      membrane in mammalian cells, the effects of changes in the cytoplasmic pH on the
      internalization of physiologically relevant, submicromolar concentrations of
      uncomplexed long-chain fatty acids were investigated in 3T3-L1 adipocytes. The
      acidification of the cytoplasm upon NH4Cl prepulsing of intact cells was
      accompanied by a rapid reduction of cellular long-chain fatty acid uptake
      (measured as the total accumulation of [9,10-3H]oleate). This was followed by a
      slow recovery to normal levels of uptake as the cytoplasmic pH recovered.
      Conventional filtration assays do not distinguish between fatty acid movement
      across the plasma membrane and intracellular steps, such as binding to
      cytoplasmic fatty acid-binding proteins or metabolism. While the in vitro binding
      of a photoreactive fatty acid, 11-m-diazirinophenoxy[11-3H]undecanoate, to a
      cytoplasmic fatty acid-binding protein was insensitive to changes in pH from pH
      7.5 to 5.5, the in vitro conversion of oleate into oleoyl-CoA by cellular acyl
      CoA synthetase decreased dramatically. Therefore, the labelling of the 15 kDa
      cytoplasmic fatty acid-binding protein in intact cells by the photoreactive fatty
      acid was used as a more direct measure of the permeation of the probe across the
      plasma membrane. Acidification of the cytoplasm resulted in an immediate
      reduction in the labelling of this protein in intact adipocytes. Its
      photolabelling recovered, however, upon the recovery of the cytoplasmic pH to
      normal levels. This was due to effects of the cytoplasmic pH on the permeation of
      the photoreactive fatty acid across the plasma membrane rather than its binding
      to the 15 kDa protein or metabolism in vivo. This is the first demonstration that
      the movement of physiologically relevant, submicromolar concentrations of
      uncomplexed long-chain fatty acids across the plasma membrane of intact cells is
      coupled to the cytoplasmic pH and suggests that it occurs by the diffusion of the
      protonated long-chain fatty acid through the lipid bilayer.

PMID- 8573081
TI  - Administration of Escherichia coli endotoxin to rat increases liver mass and
      hepatocyte volume in vivo.
AB  - We have established, in vivo, an increase in liver mass and hepatocyte volume
      after a single intraperitoneal administration, to fasted rats, of Escherichia
      coli lipopolysaccharide (0127:B8) at 3 mg/kg. The phenomenon was time- and dose
      dependent and could be prevented by treatment with polyclonal antiserum against
      tumour necrosis factor-alpha (TNF-alpha) before the endotoxin injection.
      Endotoxin caused an increase of 26% in the hepatic mass compared with fasted
      controls at 24 h. An increase of 27% in the hepatic water content underlay the
      altered hepatic mass which could not be accounted for by a change in the volume
      of hepatic blood and/or interstitial fluid (measured in vivo), suggesting an
      expansion in the hepatocellular volume. This is supported by an increase of 25%
      in the K+ content of the endotoxic livers. Morphometric study confirmed a 15%
      increase in hepatocyte volume after endotoxin administration. The data are
      discussed in the light of possible metabolic effects of increased hepatocyte
      volume.

PMID- 8573083
TI  - Insulin upstream factor 1 and a novel ubiquitous factor bind to the human islet
      amyloid polypeptide/amylin gene promoter.
AB  - The islet amyloid polypeptide (IAPP) gene is expressed primarily in the islet
      beta-cell and the peptide is co-secreted with insulin. To investigate mechanisms
      important in its regulation, we have used the electrophoretic mobility-shift
      assay and methylation interference to determine systematically sites of DNA
      protein interactions in the human IAPP promoter. We identified beta-cell-specific
      DNA-protein complexes at three sites, each of which contained a consensus binding
      site for insulin upstream factor I (IUF-I). This complex was displaced with an
      antiserum to IUF-1, confirming that IUF-1 binds to the human IAPP promoter in
      vitro. We have also identified a DNA-protein complex within the region -220/-250
      in both beta- and non-beta-cell lines. This region contains a motif with partial
      identity with the binding site for the ubiquitous transcription factor upstream
      stimulatory factor (USF), which binds to the human insulin promoter. However,
      purified USF was not able to bind to this putative site in the IAPP promoter and
      an oligonucleotide containing a functional USF-binding site was unable to
      displace binding from the IAPP oligonucleotide. Methylation interference revealed
      that the DNA-protein complex binds to a sequence that overlaps the USE-like
      sequence, and may therefore be a novel helix-loop-helix protein. These results
      suggest that, although both IAPP and insulin are beta-cell peptides, IAPP
      contains regulatory regions both common to and distinct from insulin.

PMID- 8573084
TI  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes
      phosphorylation and an increase in the activity of cytosolic phospholipase A2 in
      human neutrophils.
AB  - Incubation of human neutrophils with 500 pM granulocyte-macrophage colony
      stimulating factor (GM-CSF) results in a rapid and time-dependent increase in the
      phosphorylation of cytosolic phospholipase A2 (cPLA2), which was reflected in a
      slower electrophoretic mobility of the enzyme. The GM-CSF-induced phosphorylation
      of cPLA2 was accompanied by a parallel and time-dependent increase in the enzyme
      activity. Preincubation of neutrophils with the tyrosine kinase inhibitor
      genistein caused inhibition of the GM-CSF-stimulated phosphorylation and activity
      of cPLA2. Immunoprecipitation of the enzyme following incubation of neutrophils
      with [32P]Pi shows that cPLA2 is phosphorylated by GM-CSF. Potato acid
      phosphatase caused dephosphorylation of the enzyme, indicating that cPLA2 is
      indeed phosphorylated by GM-CSF. The subcellular distribution of cPLA2 in GM-CSF
      stimulated neutrophils revealed that the enzyme resides almost completely in the
      cytosolic fraction. Addition of Ca2+ to the lysis buffer before homogenization
      results in the translocation of the phosphorylated and the dephosphorylated forms
      of the enzyme to the membranes. Translocation of cPLA2 was also achieved after
      incubation with 0.1 microM N-formylmethionyl-leucyl-phenyl-alanine (fMLP) after
      GM-CSF stimulation and when neutrophils were challenged with the Ca2+ ionophore
      A23187. EDTA and EGTA were unable to solubilize the translocated enzyme from the
      neutrophil membranes, indicating that cPLA2 is attached to the membranes by
      strong bonds and not merely due to ionic forces exerted by Ca2+. The inability of
      GM-CSF to promote arachidonic acid mobilization is probably due to the fact that
      GM-CSF does not cause an increase in intracellular Ca2+, which is necessary for
      the translocation of the enzyme to the membranes where its substrate(s) reside.

PMID- 8573085
TI  - Asymmetric signal transduction in polarized ileal Na(+)-absorbing cells:
      carbachol activates brush-border but not basolateral-membrane PIP2-PLC and
      translocates PLC-gamma 1 only to the brush border.
AB  - In ileal Na+ absorptive cells, carbachol inhibits NaCl absorption and its
      component brush-border Na+/H+ exchanger, acting via basolateral membrane (BLM)
      receptors. This carbachol effect involves brush-border but not BLM protein kinase
      C. In the present work we describe another asymmetric aspect of signal
      transduction in these epithelial cells, this time involving phosphatidylinositol
      4,5-bisphosphate (PIP2)-specific phospholipase C (PLC). Thirty seconds and 1 min
      after carbachol treatment, brush-border PIP2-specific PLC activity increased,
      returning to control levels by 2.5 min. Involvement of brush-border tyrosine
      kinase(s) in this effect was suggested by inhibition of the carbachol effect on
      NaCl absorption by the tyrosine kinase inhibitor genistein, added to the mucosal
      but not the serosal surface. Luminal genistein pretreatment also prevented the
      carbachol-induced increase in brush-border PLC activity. In contrast, carbachol
      exposure did not change the BLM PIP2-specific PLC activity. Western analysis and
      immunoprecipitation demonstrated that PLC-gamma 1 is present in the brush border
      and that carbachol increases the PLC-gamma 1 amount in the brush border. Both the
      brush border and BLM contain PLC-beta 3 and a small amount of PLC-delta 1 but no
      PLC-beta 1, whereas BLM lacks detectable PLC-gamma 1. No change in PLC-beta 3 or
      PLC-delta 1 amount in the brush border occurred with carbachol exposure. No
      change in tyrosine phosphorylation of brush-border PLC-gamma 1 occurred with
      carbachol treatment. The Ca2+ ionophore A23187 did not alter PIP2-specific PLC
      activity in either the brush border or the BLM. These studies demonstrate that
      carbachol but not Ca2+ ionophore effects on brush-border NaCl absorption are
      associated with increases in brush-border but not BLM PIP2-specific PLC activity
      and in the amount of brush-border PLC-gamma 1, and involve tyrosine
      phosphorylation. This asymmetric aspect of epithelial signal transduction,
      together with the previous demonstration of localization of high-sensitivity IP3
      stores to the apical membrane area in intestinal epithelial cells, shows that
      different aspects of signal transduction occur at the apical and basolateral
      membranes in epithelial and requires studies in both domains to define mechanisms
      of intracellular signalling.

PMID- 8573086
TI  - Differential induction of the mitogen-activated protein kinase pathway by
      bacterial lipopolysaccharide in cultured monocytes and astrocytes.
AB  - We recently reported that cyclic AMP (cAMP) specifically inhibits
      lipopolysaccharide (LPS)-induced interleukin 1 beta (IL-1 beta) transcription
      initiation in astrocytic cells but enhances the LPS induction of IL-1 beta in
      monocytic cells. The purpose of this study was to determine how cAMP
      differentially regulates LPS-induced IL-1 beta transcription in these two cell
      types. Two essential components of the mitogen-activated protein (MAP) kinase
      signal-transduction pathway, extracellular-signal-regulated kinase (ERK2; p41
      mapk) and Raf-1, have been shown to be targets of LPS stimulation in other cell
      types, and therefore may be linked to the regulation of IL-1 beta transcription.
      In the human astrocytic cell line, U-373MG, LPS was found to strongly activate
      (and cAMP to inhibit) both ERK2 and Raf-1. In the human monocytic cell line, THP
      1, LPS minimally activated ERK2 and did not activate Raf-1. These findings
      suggest that, in astrocytic cells, elevated intracellular cAMP levels may
      negatively regulate LPS activation of IL-1 beta via the MAP kinase signalling
      pathway. In contrast, this pathway is not significantly activated by LPS in
      monocytic cells, thus inhibition by elevated intracellular cAMP levels would not
      affect IL-1 beta transcription.

PMID- 8573087
TI  - Bovine growth hormone induces oscillations in cytosolic free Ca2+ in single rat
      hepatocytes.
AB  - Single rat hepatocytes microinjected with the photoprotein aequorin generate
      oscillations in the cytosolic free Ca2+ concentration ([Ca2+]i) when stimulated
      with agonists acting through the phosphoinositide signalling pathway. We show
      here that, in single rat hepatocytes, bovine growth hormone (bGH) is able to
      induce [Ca2+]i oscillations which display similarities with oscillations induced
      by phenylephrine. Thus the rate of rise of intracellular Ca2+ in each oscillation
      closely resembles that induced by Ins(1,4,5)P3-mediated agonists. However, the
      duration of bGH-induced oscillations increases with agonist concentration, in
      contrast to phenylephrine-induced oscillations, which undergo an increase in
      frequency as the agonist concentration is raised, without any increase in the
      duration of individual oscillations.

PMID- 8573088
TI  - Phospholipase D activation by P2Z-purinoceptor agonists in human lymphocytes is
      dependent on bivalent cation influx.
AB  - The role of bivalent cations in ATP-stimulated phospholipase D (PLD) activity was
      investigated in human leukaemic lymphocytes. Cells were labelled with [3H]oleic
      acid and incubated with extracellular ATP or benzoylbenzoic ATP in the presence
      of 1 mM Ca2+ and butanol, and PLD activity was assayed by the accumulation of
      [3H]phosphatidylbutanol ([3H]PBut). ATP stimulated PLD activity in a dose
      dependent manner, and the inhibitory effects of suramin, oxidized ATP and
      extracellular Mg2+ suggested that the effect of ATP was mediated by P2Z
      purinoceptors known to be present on lymphocytes. Thapsigargin increased
      cytosolic [Ca2+] but did not stimulate PLD activity, whereas preloading cells
      with a Ca2+ chelator reduced cytosolic [Ca2+] and, paradoxically, potentiated ATP
      stimulated [3H]PBut accumulation. ATP-stimulated [3H]PBut formation was supported
      by both Ba2+ and Sr2+ when they were substituted for extracellular Ca2+. Addition
      of EGTA to block bivalent cation influx inhibited the majority of ATP-stimulated
      PLD activity. Furthermore ATP-stimulated PLD activity showed a linear
      relationship to extracellular [Ba2+], and ATP-induced 133Ba2+ influx also had a
      linear dependence on extracellular [Ba2+]. These results suggest that ATP
      stimulates PLD activity in direct proportion to the influx of bivalent cations
      through the P2Z-purinoceptor ion channel and that this PLD activity is
      insensitive to changes in bulk cytosolic [Ca2+].

PMID- 8573089
TI  - Hepoxilin A3-specific binding in human neutrophils.
AB  - Hepoxilins have been shown to release calcium from intracellular stores in human
      neutrophils [Dho, Grinstein, Corey, Su and Pace-Asciak (1990) Biochem. J. 266, 63
      68; Laneuville, Reynaud, Grinstein, Nigam and Pace-Asciak (1993) Biochem. J. 295,
      393-397]. In this paper we report that tritium-labelled hepoxilin A3 (8S) binds
      to broken neutrophil membranes in a time-, substrate- and temperature-dependent
      fashion. Specific binding was displaced with unlabelled hepoxilin A3. Specific
      binding was greatest at 37 degrees C. Competitive binding was best observed with
      unlabelled hepoxilin A3 (8S); the glutathione conjugate, HxA3-C (8S or 8R), or
      12(S)-hydroxyeicosatetraenoic acid was less active. Similarly inactive in
      displacing the bound radiolabelled hepoxilin A3 was leukotriene B4 as well as a
      variety of prostaglandins and thromboxane B2. Formylmethionyl-leucylphenylalanine
      was similarly inactive in competing for the hepoxilin binding sites. Specific
      binding was inhibited by pretreatment of the broken membranes during 30 min at 37
      degrees C with proteinase K, while specific binding of the intact cells was
      unaffected. Scatchard analysis of binding data revealed a single population of
      binding sites with apparent KD and Bmax. of 79.3 +/- 9.1 nM and 8.86 +/- 1.4
      pmol/ml per 2 x 10(6) cells (+/- S.E.M.) respectively reflecting approx. 2.67 x
      10(6) sites/cell. These results demonstrate for the first time that neutrophils
      contain specific binding sites to hepoxilin A3.

PMID- 8573090
TI  - Analysis of amplicons containing the esterase genes responsible for insecticide
      resistance in the peach-potato aphid Myzus persicae (Sulzer).
AB  - The amplification of genes encoding an insecticide-detoxifying esterase (E4) in
      the peach-potato aphid Myzus persicae is one of the few examples where this
      genetic phenomenon has been shown to be involved in the response of an intact
      higher organism to artificial selection. Here we report quantitative and
      qualitative studies of the repeat units (amplicons) containing the E4 genes in a
      highly resistant aphid clone. Initial studies to quantify esterase sequences
      showed a 5-11-fold increase in resistant aphids compared with susceptible aphids,
      suggesting the presence of 10-22 gene copies per diploid genome. A more incisive
      analysis by pulsed-field gel electrophoresis confirmed the presence of about 12
      copies of the E4 gene and showed them to be on about 24 kb amplicons, arranged as
      a tandem array of direct repeats. This, together with previous results from
      crossing experiments and with recent in situ hybridization studies, confirms that
      the E4 gene amplification in this aphid clone is heterozygous at a single locus.
      However, these data show that the gene amplification alone cannot account for the
      approx. 60 times higher levels of E4 protein and its mRNA present in this aphid
      clone, and therefore resistance must involve changes in both esterase gene copy
      number and gene expression.

PMID- 8573091
TI  - Spermine suppresses the activation of human neutrophil NADPH oxidase in cell-free
      and semi-recombinant systems.
AB  - Spermine, a cellular polyamine, down-regulates O2- generation in human
      neutrophils stimulated by receptor-linked agonist [Ogata, Tamura and Takeshita
      (1992) Biochem. Biophys. Res. Commun. 182, 20-26]. In this study, to elucidate
      the mechanism for the inhibition, the effect of spermine on cell-free activation
      of the O2- generating enzyme (NADPH oxidase) was examined. Spermine suppressed
      the SDS-induced activation of NADPH oxidase in a dose-dependent manner with an
      IC50 of 18 microM. The inhibition was specific for spermine over its precursor
      amines, spermidine and putrescine. Spermine did not alter the Km for NADPH or the
      optimal concentration of SDS for activation. The amine was inhibitory only when
      added before activation, indicating that it affects the activation process rather
      than the enzyme's activity. An increased concentration of cytosol partly
      prevented the inhibition by spermine. In semi-recombinant cell-free system,
      spermine inhibited the activation of NADPH oxidase as effectively as in the cell
      free system (IC50 = 13 microM). Pretreatment of each recombinant cytosolic
      component with spermine revealed that they (especially p67phox) are sensitive to
      spermine. These results suggest that spermine interacts with cytosolic
      component(s) and impairs the assembly of NADPH oxidase.

PMID- 8573092
TI  - Inhibition of human pancreatic proteinases by mucus proteinase inhibitor, eglin c
      and aprotinin.
AB  - The kinetic investigation of the inhibition of human pancreatic trypsin 1,
      trypsin 2 and chymotrypsin A by mucus proteinase inhibitor, eglin c and aprotinin
      reveals that (i) the first protein is a potent inhibitor of chymotrypsin A (kass.
      = 1.4 x 10(6) M-1.s-1, Ki = 71 pM) but forms loose complexes with trypsin 1 (Ki =
      0.5 microM) and trypsin 2 (Ki = 18 nM), (ii) eglin c does not inhibit the two
      trypsins but forms a tight complex with chymotrypsin A (kass. = 3.3 x 10(6) M-1.s
      1, Ki < 0.1 nM) and (iii) aprotinin is a potent inhibitor of trypsin 1 (kass. = 1
      x 10(6) M-1.s-1, Ki < 0.2 nM) and trypsin 2 (kass. = 2.4 x 10(5) M-1.s-1, Ki < 1
      nM) but forms a loose complex with chymotrypsin A (Ki = 0.17 microM). These data,
      together with those published previously on human pancreatic elastase, suggest
      that a cocktail of aprotinin + eglin c might be a better intensive-care drug for
      acute pancreatitis than aprotinin alone, because it will efficiently inhibit all
      four human pancreatic proteinases. On the other hand, human gastric juice
      inactivates mucus proteinase inhibitor by pepsin-mediated cleavage. This
      indicates that the fraction of mucus proteinase inhibitor that reaches the
      stomach following aerosol delivery to cystic fibrosis patients does not reach the
      duodenum in an active form and, therefore, does not aggravate the pancreatic
      insufficiency of these patients.

PMID- 8573093
TI  - Two-domain haemoglobin of the blood clam Barbatia lima resulted from the recent
      gene duplication of the single-domain delta chain.
AB  - The blood clam Barbatia lima subsp. from Amami-Oshima, Japan, expresses three
      types of haemoglobins in erythrocytes: a tetramer (alpha 2 beta 2), a homodimer
      (delta 2) and a polymer consisting of two kinds of chains, a 34 kDa two-domain
      (2D) globin and a delta chain. This is in sharp contrast to the congeneric clams
      B. reeveana (a North American species) and B. lima from Kochi, Japan, each
      containing a tetramer and a polymer consisting of the 2D globin, but not the
      delta chain. We have determined the cDNA-derived amino acid sequences of all four
      chains, alpha (163 residues), beta (155 residues), delta (152 residues) and 2D
      (308 residues) of B. lima (Amami-Oshima). The alpha chain has an extremely long N
      terminal extension of 20 residues that may form a 'pre-A helix', and this makes
      the alpha chain the longest known globin. B. lima alpha and beta chains show
      about 50% sequence identity with the alpha and beta chains, respectively, of
      tetrameric haemoglobin from a related clam, Anadara trapezia. The B. lima
      homodimeric delta chain shows 71-74% identity with each of the two domains of the
      2D chain, but only 39% identity with the homodimeric gamma chain of Anadara. In
      addition, the alignment of amino acid sequences of the delta chain and the two
      domains of the 2D chain revealed that the delta chain lacks one amino acid (Lys)
      at the C-terminus, suggesting that the C-terminal Lys (codon AAA or AAG) of the
      two domains of 2D chain could result from the stop codon TAA in the delta chain
      by nucleotide substitutions. These results, together with the fact that the delta
      and 2D chains form a polymeric haemoglobin, indicates that the delta chain is the
      ancestral single-domain globin for the 2D globin. The delta chain is expressed
      only in B. lima (Amami-Oshima), and appears to be a relic of molecular evolution.

PMID- 8573095
TI  - Amyloid beta 1-42 deposits do not lead to Alzheimer's neuritic plaques in aged
      dogs.
AB  - In alzheimer's disease, amyloid beta (A beta) is deposited in senile plaques and
      amyloid angiopathy. Longer A beta peptides, which extend to residue 42 (A beta
      42), have been suggested to be critical for the seeding of amyloid. Aged dogs
      develop cerebral vessel amyloid and parenchymal preamyloid lesions. Preamyloid in
      humans is related to senile plaques, whereas in dogs such progression is rare. We
      evaluated the composition of aged canine vessel amyloid and preamyloid both
      biochemically and immunohistochemically. The vessel amyloid extended mainly to
      residue 40 (A beta 40), while preamyloid contained a mixture of A beta 17-42 and
      A beta 42, with minimal A beta 40. Our results suggest other factors besides A
      beta 42 are important for neuritic plaque formation.

PMID- 8573094
TI  - Insulin-mediated inhibition of apolipoprotein B secretion requires an
      intracellular trafficking event and phosphatidylinositol 3-kinase activation:
      studies with brefeldin A and wortmannin in primary cultures of rat hepatocytes.
AB  - Insulin inhibition of the secretion of apolipoprotein B (apo B) was studied in
      primary cultures of rat hepatocytes by using brefeldin A (BFA), an inhibitor of
      protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus, and
      by using the phosphatidylinositol 3-kinase (PI 3-K) inhibitor wortmannin.
      Incubation of hepatocytes with BFA (10 micrograms/ml) for 1 h inhibited the
      subsequent secretion of apo B, albumin and transferrin for up to 3 h. BFA
      treatment resulted in the time-dependent accumulation in cells of [14C]leucine
      labelled proteins and apo B. Under conditions where insulin decreased total apo B
      (cell plus secreted), BFA blocked the insulin-dependent effect. These results
      suggest that export of apo B from the ER is a prerequisite for the observed
      insulin effect. Treatment of hepatocytes with wortmannin for 20 min abolished
      insulin inhibition of apo B secretion, suggesting that the insulin effect on the
      apo B pathway involves activation of PI 3-K. Enzyme inhibitor studies indicate
      that chymostatin and (+)-(2S,3S)-3-[(S)-methyl-1-(3-methylbutylcarbamoyl)
      butylcarba moyl]-2- oxiranecarboxylate (E-64-c) partially block insulin effects
      on apo B compared with leupeptin, which had no discernible effect. The cell
      permeable derivative of E-64-c, EST, and N-Ac-Leu-Leu-norleucinal (ALLN) were
      most effective in blocking insulin effects on apo B. These results suggest that
      insulin action on apo B in primary rat hepatocytes involves (1) vesicular
      movement of apo B from the ER; (2) activation of PI 3-K and (3) a cellular
      protease that is either a cysteine- or calcium-activated neutral protease.

PMID- 8573096
TI  - Reduction pathway of cis-5 unsaturated fatty acids in intact rat-liver and rat
      heart mitochondria: assessment with stable-isotype-labelled substrates.
AB  - Besides the conventional isomerase-mediated pathway, unsaturated fatty acids with
      old-numbered double bonds are also metabolized by reduction pathways with NADPH
      as cofactor. The relative contributions of these pathways were measured in intact
      rat-liver and rat-heart mitochondria with a novel stable isotope tracer
      technique. A mixture of equal amounts of unlabelled cis-5-enoyl-CoA and 13C4
      labelled acyl-CoA of equal chain lengths was incubated with mitochondria. The
      isotope distribution of 3-hydroxy fatty acids produced from the first cycle of
      beta-oxidation was analysed with selected ion monitoring by gas chromatograph
      mass spectrometer. 3-Hydroxy fatty acids produced from the reduction pathway of
      unsaturated fatty acids were unlabelled (m + 0) whereas those produced from
      saturated fatty acids were labelled (m + 4). The m + 0 content serves to indicate
      the extent of reduction pathway. Rotenone treatment was used to switch the
      pathway completely to reduction. The extent of m + 0 enrichment in untreated
      mitochondria normalized to the m + 0 enrichment of rotenone-treated mitochondria
      was the percentage of reduction pathway. With this technique, cis-4-decenoate was
      found to be metabolized completely by the reduction pathway in both liver and
      heart mitochondria. cis-5-Dodecenoate was metabolized essentially by the
      reduction pathway in liver mitochondria, but only to 75% in heart mitochondria.
      When the chain length was extended to cis-5-tetradecenoate, the reduction pathway
      in liver mitochondria decreased to 86% and that in heart mitochondria to 65%. The
      effects of carnitine, clofibrate and other conditions on the reduction pathway
      were also studied. Enrichments of the label on saturated fatty acids and 3
      hydroxy fatty acids indicated that the major pathway of reduction was not by the
      direct reduction of the cis-5 double bond. Instead, it is most probably by a
      pathway that does not involve forming a reduced saturated fatty acid first.

PMID- 8573097
TI  - Biosynthesis of dermatan sulphate. Defructosylated Escherichia coli K4 capsular
      polysaccharide as a substrate for the D-glucuronyl C-5 epimerase, and an
      indication of a two-base reaction mechanism.
AB  - The capsular polysaccharide from Escherichia coli K4 consists of a chondroitin
      ([GlcA(beta 1-->3)GalNAc(beta 1-->4)]n) backbone, to which beta-fructofuranose
      units are linked to C-3 of D-glucuronic acid (GlcA) residues. Removal of the
      fructose units by mild acid hydrolysis provided a substrate for the GlcA C-5
      epimerase, which is involved in the generation of L-iduronic acid (IdoA) units
      during dermatan sulphate biosynthesis. Incubation of this substrate with
      solubilized fibroblast microsomal enzyme in the presence of 3H2O resulted in the
      incorporation of tritium at C-5 of hexuronyl units. A Km of 67 x 10(-6) M
      hexuronic acid (equivalent to disaccharide units) was determined, which is
      similar to that (80 x 10(-6) M) obtained for dermatan (desulphated dermatan
      sulphate). Vmax was about 4 times higher with dermatan than with the K4
      substrate. A defructosylated K4 polysaccharide isolated after incubation of
      bacteria with D-[5-3H]glucose released 3H2O on reaction with the epimerase, and
      thus could be used to assay the enzyme. Incubation of a K4 substrate with
      solubilized microsomal epimerase for 6 h in the presence of 3H2O resulted in the
      formation of about 5% IdoA and approximately equal amounts of 3H in GlcA and
      IdoA. A corresponding incubation of dermatan yielded approx. 22% GlcA, which
      contained virtually all the 3H label. These results are tentatively explained in
      terms of a two-base reaction mechanism, involving a monoprotic L-ido-specific
      base and a polyprotic D-gluco-specific base. Most of the IdoA residues generated
      by the enzyme occurred singly, although some formation of two or three
      consecutive IdoA-containing disaccharide units was observed.

PMID- 8573098
TI  - Occurrence of a cytosolic neutral chitobiase activity involved in oligomannoside
      degradation: a study with Madin-Darby bovine kidney (MDBK) cells.
AB  - Neutral oligomannosides possessing one GlcNAc (OS-Gn1) and two GlcNAc (Os-Gn2) at
      the reducing end have been reported to be released during the N-glycosylation
      process in various biological models. To investigate which enzyme is responsible
      for OS-Gn1 formation, we used the Madin-Darby bovine kidney (MDBK) cell line
      which exhibits neither lysosomal chitobiase nor endoglucosaminidase activities.
      However, these cells produced OS-Gn1 and we showed that a neutral chitobiase is
      responsible for the transformation of OS-Gn2 into OS-Gn1. Using streptolysin O
      permeabilized MDBK cells, we demonstrated that this neutral chitobiase activity
      is located in the cytosolic compartment and is active on oligomannoside species
      released during the N-glycosylation process.

PMID- 8573099
TI  - Structural organization of the rat branched-chain 2-oxo-acid dehydrogenase kinase
      gene and partial characterization of the promoter-regulatory region.
AB  - The gene encoding the rat branched-chain 2-oxo-acid dehydrogenase kinase (EC
      2.7.1.115) has been isolated and partially characterized. The entire gene,
      including the promoter-regulatory region, spans 6 kb and contains 11 exons. The
      5'-untranslated region comprising 264 bp is interrupted by intron 1 which is 581
      bp in size. The complete in-frame sequence of intron 7 encodes the 49 amino acid
      insert previously reported to be present in the larger isoform of the rat kinase
      (Harris, Popov, Shimomura, Zhao, Jaskiewicz, Nanaumi and Suzuki (1992) Adv.
      Enzyme Regul. 32, 267-284). Sequencing of the 679 bp of the 5'-flanking region
      showed the absence of a canonical TATA box, similar to other branched-chain 2-oxo
      acid dehydrogenase-complex genes. Several candidate cis-acting elements are
      present. These include CAAT boxes, Sp-1-binding sites, GCN-4 sites, CCAAT
      enhancer binding-protein sites (C/EBP) and glucocorticoid-responsive element
      (GRE) sites. Also present are a pair of direct repeats of unknown function. The
      luciferase-reporter assay showed that promoter activity is markedly higher in
      normal rat kidney (NRK-52E) cells than in rat hepatoma (FTO-2B) cells, and that
      the 5'-flanking region between bases -449 and +264 is both necessary and
      sufficient for basal transcription of the kinase gene.

PMID- 8573100
TI  - Properties of the human arginine vasopressin V2 receptor after site-directed
      mutagenesis of its putative palmitoylation site.
AB  - Most G-protein-coupled receptors have conserved cysteine residues in their C
      terminal cytoplasmic domain that appear to be generally palmitoylated. An example
      is the human arginine vasopressin V2 receptor with cysteine residues at positions
      341 and 342. Site-directed mutagenesis of the putative palmitoylation site was
      used to study the significance of palmitoylation for the V2 receptor. A
      multifunctional expression plasmid was constructed by cloning the V2 receptor
      cDNA into the vector pCDNAI.Neo. The resulting plasmid allowed site-directed
      mutagenesis experiments without subcloning, and stable and transient expression
      of the V2 receptor in Ltk- and COS.M6 cells respectively. The conserved cysteine
      residues Cys-341 and Cys-342 were placed by serine residues, yielding the single
      mutants C-341S and C-342S and the double mutant C-341S/C-342S. Functional
      expression in stably transfected Ltk- cells showed that the affinity of the three
      mutant receptors for arginine vasopressin was not altered. In contrast with the
      activation of adenylate cyclase through beta 2 adrenergic receptors, arginine
      vasopressin stimulated adenylate cyclase to the same extent and with similar EC50
      values in both wild-type and mutant receptors. Transient expression of the C
      341S/C-342S mutant receptor in COS.M6 cells confirmed an unaltered affinity of
      the mutant receptor for arginine vasopressin. However, the number of arginine
      vasopressin-binding sites on the cell surface was reduced by 30%, suggesting that
      the transport of the mutant receptor to the cell surface was impaired. In
      addition, the decrease in detectable arginine vasopressin-binding sites on the
      cell surface following pre-exposure to hormone was reduced, indicating that the
      sequestration/internalization of the mutant receptor on the cell surface was
      affected. The present data indicate that palmitoylation of the V2 receptor is
      important for intracellular trafficking and/or sequestration/internalization but
      not for agonist binding or activation of the Gs/adenylate cyclase system.

PMID- 8573101
TI  - Effect of cyclic AMP and prostaglandin E2 on the induction of nitric oxide- and
      prostanoid-forming pathways in cultured rat mesangial cells.
AB  - Cyclic AMP (cAMP) represents an important cellular signalling molecule. We
      analysed the effect of dibutyryl cAMP (db-cAMP), a cell-permeable and stable
      derivative of cAMP, on the regulation and expression of cyclo-oxygenase 2,
      inducible NO synthase and argininosuccinate synthetase. We observed different
      transcriptional regulation of these enzymes depending on the db-cAMP
      concentration used. Low concentrations of db-cAMP in the range 10-50 microM
      elevated levels of cyclo-oxygenase 2 mRNA, protein and activity, but not the
      respective mRNA and protein concentrations of the inducible NO synthase or
      argininosuccinate synthetase. At higher concentrations a massive induction of the
      latter two enzymes was also apparent. Expression of prostacyclin synthase and
      argininosuccinate lyase, secondary enzymes of NO- and prostanoid-forming
      pathways, was not stimulated by db-cAMP. Prostaglandin E2, known to be an
      intracellular physiological trigger of cAMP formation, stimulated only
      cyclooxygenase 2 expression and activity at a concentration of 10 microM, and not
      inducible NO synthase. The induction of the mRNA for the transcription factors
      JunB and p65, a component of the NF kappa B complex, by prostaglandin treatment
      of the cells might be a possible mechanistic explanation for this observation.

PMID- 8573102
TI  - Granulocyte/macrophage colony-stimulating factor is an intrinsic keratinocyte
      derived growth factor for human melanocytes in UVA-induced melanosis.
AB  - Recently we demonstrated that endothelins secreted from human keratinocytes act
      as intrinsic mitogens and melanogens for human melanocytes in UVB-induced
      melanosis. We show here that UVA-induced melanosis is associated with other
      keratinocyte-derived growth factors, secretion of which is specifically
      stimulated after exposure of human keratinocytes to UVA. Medium conditioned by
      UVA-exposed human keratinocytes elicited a significant increase in DNA synthesis
      by cultured human melanocytes in a UVA dose-dependent manner. Analysis of
      endothelin-1 and interleukin (IL)-1 alpha in the conditioned medium by ELISA,
      both of which are major keratinocyte-derived cytokines involved in UVB-associated
      melanocyte activation, revealed that UVA exposure did not cause human
      keratinocytes to stimulate the secretion of the two cytokines. In contrast, the
      levels of several other cytokines such as IL-6, IL-8 and granulocyte/macrophage
      colony-stimulating factor (GM-CSF) were significantly increased in the
      conditioned medium of human keratinocytes after exposure to UVA at a dose of 1.0
      J/cm2. The gel chromatographic profile of UVA-exposed keratinocyte-conditioned
      medium demonstrated that there were two factors (P-1 and P-2) with molecular
      masses of approx. 20 and 1 kDa respectively that stimulate DNA synthesis in human
      melanocytes, and the larger species (P-1) also increased melanization as assessed
      by [14C]thiouracil incorporation. Quantitative analysis of cytokines in
      chromatographic fractions by ELISA revealed the P-1 fraction to be consistent
      with the molecular mass profile of GM-CSF. Furthermore the stimulatory effect of
      the P-1 fraction on DNA synthesis in human melanocytes was neutralized by
      antibodies to GM-CSF, but not to basic fibroblast growth factor or stem cell
      factor. Binding and proliferation assays with recombinant GM-CSF demonstrated
      that human melanocytes possess specific binding sites for GM-CSF(Kd 2.11 nM;
      binding sites, 2.5-3.5 x 10(4) per cell), and recombinant GM-CSF at
      concentrations of more than 10 nM significantly stimulated DNA synthesis and
      melanization. These findings suggest that GM-CSF secreted by keratinocytes plays
      an essential role in the maintenance of melanocyte proliferation and UVA-induced
      pigmentation in the epidermis.

PMID- 8573103
TI  - Site-directed mutagenesis of monocyte chemoattractant protein-1 identifies two
      regions of the polypeptide essential for biological activity.
AB  - Monocyte chemoattractant protein-1 (MCP-1) mediates monocyte migration into
      tissues in inflammatory diseases and atherosclerosis. We have investigated
      structure-activity relationships for human MCP-1. Mutations were introduced based
      upon differences between MCP-1 and the structurally related but functionally
      distinct molecule interleukin-8 (IL-8). Mutant proteins produced using the
      baculovirus/insect cell expression system were purified and their ability to
      stimulate monocyte chemotaxis and elevation of intracellular calcium in THP-1
      monocytic leukaemia cells was measured. Two regions in MCP-1 were identified as
      important for its biological activity. One region consists of the sequence Thr
      Cys-Cys-Tyr (amino acids 10-13). Point mutations of Thr-10 to Arg and Tyr-13 to
      Ile greatly lowered MCP-1 activity. The second functionally important region is
      formed by Ser-34 and Lys-35. Insertion of a Pro between these two residues, or
      their substitution by the sequence Gly-Pro-His, caused nearly complete loss of
      MCP-1 activity. Competition binding experiments showed that the mutations that
      affected activity also lowered the ability to compete with wild-type MCP-1 for
      receptors on THP-1 cells. Point mutations at positions 8, 15, 30, 37, 38 and 68
      had little effect on MCP-1 activity. The important regions that we have
      identified in MCP-1 correspond with previously identified functionally important
      regions of IL-8, suggesting that the two molecules bind to their respective
      receptors by similar contacts.

PMID- 8573104
TI  - Interleukin-13 inhibits inducible nitric oxide synthase expression in human
      mesangial cells.
AB  - The synthesis of nitric oxide in inflammatory situations requires the expression
      of an inducible isoform of nitric oxide synthase (iNOS). Human mesangial cells
      (HMC) express an iNOS enzyme after exposure to multiple co-stimuli. In this study
      we have observed that while tumour necrosis factor-alpha, interleukin (IL)-1
      beta, interferon-gamma and bacterial lipopolysaccharide (LPS) were unable to
      significantly induce NO synthesis when used alone, they induced an evident
      stimulation of NO synthesis when used in various combinations. A mixture of the
      three cytokines (CM) and LPS resulted in a 10-15-fold stimulation of NO synthesis
      over control values which started to be significant after 16 h. The addition of
      IL-13, a cytokine with anti-inflammatory properties, inhibited CM/LPS-induced NO
      synthesis in a concentration-dependent manner. A marked inhibitory effect (60
      65%) could be observed when HMC were treated with IL-13 (10 ng/ml) 24 h before,
      at the same time as, or even 4 h after the addition of CM/LPS. This inhibitory
      effect was still significant (25%) when IL-13 was added 16 h after CM/LPS.
      Northern analysis showed that IL-13-mediated iNOS inhibition was closely
      correlated with the suppression of iNOS mRNA expression. These results identify
      IL-13 as a powerful regulatory tool for the inhibition of NO synthesis in human
      cells, a property which may be pathophysiologically relevant in NO-related
      inflammatory processes.

PMID- 8573105
TI  - Ability of methotrexate to inhibit translocation to the cytosol of dihydrofolate
      reductase fused to diphtheria toxin.
AB  - A fusion protein consisting of dihydrofolate reductase and diphtheria toxin A
      fragment was made by genetically linking cDNA for the two proteins followed by in
      vitro transcription and translation in a rabbit reticulocyte lysate system. The
      dihydrofolate reductase in the fusion protein exhibited enzyme activity and, in
      the presence of methotrexate which imposes a tight structure on dihydrofolate
      reductase, it was trypsin resistant, indicating that it was correctly folded.
      When reconstituted with diphtheria toxin B-fragment, it bound specifically to
      diphtheria toxin receptors and was translocated into cells upon exposure to low
      pH. Methotrexate prevented the translocation. Protein synthesis was inhibited in
      cells incubated with the reconstituted fusion protein, but the inhibition was
      reduced in the presence of methotrexate. We also made a fusion protein containing
      a mutated dihydrofolate reductase with much lower affinity to methotrexate.
      Methotrexate did not prevent translocation of this protein. The data indicate
      that methotrexate prevents translocation of the fusion protein containing wild
      type dihydrofolate reductase by imposing a tight structure on to the enzyme.

PMID- 8573106
TI  - Acidocalcisomes in Toxoplasma gondii tachyzoites.
AB  - Toxoplasma gondii tachyzoites were loaded with the fluorescent indicator fura 2
      to investigate the transport mechanisms involved in maintaining their
      intracellular Ca2+ homoeostasis. The mitochondrial ATPase inhibitor oligomycin
      and the endoplasmic-reticulum Ca(2+)-ATPase inhibitor thapsigargin increased the
      intracellular Ca2+ concentration ([Ca2+]i), thus indicating the requirement for
      ATP and the involvement of the endoplasmic reticulum in maintaining intracellular
      Ca2+ homoeostasis. The effect of thapsigargin was more accentuated in the
      presence of extracellular Ca2+, clearly showing that, as occurs with other
      eukaryotic cells, depletion of intracellular Ca2+ pools led to an increase in the
      uptake of Ca2+ from the extracellular medium. In addition to these results, we
      found evidence that, in contrast with what occurs in mammalian cells, T. gondii
      tachyzoites possess a significant amount of Ca2+ stored in an acidic compartment,
      termed the acidocalcisome, as indicated by: (1) the increase in [Ca2+]i induced
      by bafilomycin A1 (a specific inhibitor of H(+)-ATPases), nigericin (a K+/H+
      exchanger) or the weak base NH4Cl, in the nominal absence of extracellular Ca2+
      to preclude Ca2+ entry; and (2) the effect of ionomycin, a Ca(2+)-releasing
      ionophore that cannot take Ca2+ out of acidic organelles and that was more
      effective after alkalinization of these compartments by addition of bafilomycin
      A1, nigericin or NH4Cl. Considering the relative importance of the ionomycin
      releasable and the ionomycin + NH4Cl-releasable Ca2+ pools, it is apparent that
      T. gondii tachyzoites contain a significant amount of Ca2+ stored in
      acidocalcisomes.

PMID- 8573107
TI  - Calmidazolium leads to an increase in the cytosolic Ca2+ concentration in
      Dictyostelium discoideum by induction of Ca2+ release from intracellular stores
      and influx of extracellular Ca2+.
AB  - The Ca2+ stores of Dictyostelium discoideum amoebae take part in control of
      homoeostasis of the cytosolic free Ca2+ concentration ([Ca2+]i) and the cyclic
      AMP-induced [Ca2+]i-signalling cascade. In order to characterize regulatory
      mechanisms of these stores, we incubated cells with the calmodulin antagonist
      calmidazolium. Measurement of permeabilized and intact cells in suspension with a
      Ca(2+)-sensitive electrode revealed that calmidazolium induced Ca2+ release from
      intracellular stores, influx of Ca2+ across the plasma membrane and subsequent
      efflux. In single fura-2-loaded cells calmidazolium evoked rapid and global
      transient elevations of [Ca2+]i. Other calmodulin antagonists (trifluoperazine,
      chlorpromazine, fendiline and W7) also induced transient elevations of [Ca2+]i,
      which were, however, slower and observed in fewer cells. The calmidazolium
      induced influx of extracellular Ca2+ was inhibited by preincubation with 2,5-di
      (t-butyl)-1, 4-hydroquinone (BHQ) and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD
      Cl), both known to interact with pumps of the inositol 1,4,5-trisphosphate (IP3)
      sensitive store, and by the V-type H(+)-ATPase inhibitor bafilomycin A1, which
      affects the acidosomal Ca2+ store. Incubation with pump inhibitors did not itself
      induce changes in [Ca2+]i. We conclude that the effects of calmidazolium are, at
      least in part, mediated by its calmodulin-antagonizing properties, that it acts
      by inducing Ca2+ release from filled storage compartments, and that its target of
      action is both the IP3-sensitive store and the acidosome; emptying of these
      stores leads to influx of extracellular Ca2+.

PMID- 8573108
TI  - Effects of lipids on nucleotide inhibition of wheat-germ aspartate
      transcarbamoylase: evidence of an additional level of control?
AB  - Wheat-germ aspartate transcarbamoylase, a monofunctional trimer, is strongly
      inhibited by uridine 5'-monophosphate (UMP), which shows kinetic interactions
      with the substrate, carbamoyl phosphate, suggesting a classical allosteric
      mechanism of regulation. Inhibition of the purified enzyme by UMP was amplified
      in the presence of a variety of ionic lipids at concentrations low enough to
      preclude denaturation. In the absence of UMP, most of these compounds had no
      kinetic effect or were slightly activating. Two phospholipids did not show the
      effect. In a homologous series of fatty acids (C6-C16), the potentiating effect
      was only seen with homologues greater than C8, reaching a maximum at C12. The
      effect of dodecanoate (C12) on kinetic cooperativity (UMP as variable ligand) was
      studied. At each of several fixed concentrations of carbamoyl phosphate,
      dodecanoate had a pronounced effect on the half-saturating concentration of UMP,
      which was reduced by about half in every case, indicating substantially tighter
      binding of UMP. However, dodecanoate had relatively little effect on the kinetic
      Hill coefficient for the cooperativity of UMP. The possible metabolic
      significance of these effects is discussed.

PMID- 8573109
TI  - Purification by cobalamin-Sepharose affinity chromatography and intrinsic factor
      binding activity of an extramembrane proteolytic product from pig ileal mucosa.
AB  - We have purified a cobalamin-binding protein obtained by papain digestion of pig
      intestine by cobalamin-AH-Sepharose affinity chromatography, with a purification
      factor of 17,300, a yield of 63% and a cobalamin-binding activity of 11,260
      pmol/mg of protein. The protein contained 3.8% carbohydrate and was O- and N
      glycosylated. Its molecular mass was 69 kDa on SDS/PAGE and its isoelectric point
      was 5.1. It had a binding activity for both [57Co]cobalamin and [57Co]cobalamin
      intrinsic factor in native PAGE autoradiography and it inhibited the binding of
      intrinsic factor to the intact intestinal receptor with an IC50 of 49.31 nmol/l
      in a radioisotope assay. In conclusion, the purified protein shared a binding
      activity for both cobalamin and intrinsic factor-cobalamin complexes and could
      correspond to the extracellular domain of the ileal intrinsic factor receptor.

PMID- 8573110
TI  - Comparison of lipid aggregation and self-aggregation activities of pulmonary
      surfactant-associated protein A.
AB  - 1. We compared the Ca2+ dependence of the self-aggregation of surfactant protein
      A (SP-A) with that of vesicle aggregation induced by SP-A. The Ca2+ concentration
      required for half-maximal activity of lipid aggregation was 0.74 +/- 0.29 microM
      (n = 4) for pig SP-A and 98 +/- 5 microM (n = 2) for dog SP-A. In contrast, the
      threshold concentration of Ca2+ required to induce self-association of both pig
      and dog SP-A was 0.5 mM. The Ca2+ concentration needed for half-maximal self
      association was 2.36 +/- 0.15 mM (n = 4) and 0.70 +/- 0.06 mM (n = 2) for pig and
      dog SP-A respectively. 2. We also compared the effect of Ca2+ on the trypsin
      sensitivity of lipid-free and membrane-bound SP-A. At 1 microM Ca2+, the tryptic
      digestion patterns of dog and pig lipid-free SP-A were quite different. Dog SP-A
      was very sensitive to proteolysis, being almost completely digested by 30 min,
      while pig SP-A was very resistant, even after 12 h. After protein aggregation of
      lipid-free SP-A (at 5 mM Ca2+), the accessibility of the trypsin cleavage targets
      of the protein depended on the SP-A species (self-aggregated pig SP-A became more
      sensitive to degradation than its non-aggregated form, whereas self-aggregated
      dog SP-A was less susceptible). In contrast, membrane-bound SP-A, from either pig
      or dog, was clearly protected from trypsin degradation at both low (1 microM) or
      high (1 mM) Ca2+ concentrations. The protection was slightly higher at 1 mM Ca2+
      when the extent of lipid/SP-A aggregates was maximal. 3. On the other hand,
      vesicle aggregation activity of SP-A was decreased by 30-40% by removing the
      oligosaccharide moiety of the protein, whereas self-aggregation was not
      influenced by deglycosylation. The presence of mannan (at concentrations not
      lower than 10 micrograms/microliters) decreased vesicle aggregation induced by
      dog and pig SP-A by a mechanism that is independent of the binding of mannan to
      the carbohydrate-binding domain of SP-A. Self-aggregation of SP-A was not
      affected by the presence of sugars. 4. From these results, we conclude that: (1)
      the process of lipid aggregation induced by SP-A cannot be correlated with that
      of self-association of the protein occurring at supramillimolar concentrations of
      Ca2+; and (2) the N-linked carbohydrate moiety of SP-A and the ability of SP-A to
      bind carbohydrates are not involved in lipid aggregation.

PMID- 8573112
TI  - Continuous HGF supply from HGF-expressing fibroblasts transplanted into spleen
      prevents CCl4-induced acute liver injury in rats.
AB  - Hepatocyte growth factor (HGF), first identified as a potent mitogen for mature
      hepatocytes, has been reported to have various activities. We investigated
      protective effect of continuous HGF supply on carbon tetrachloride (CCl4)-induced
      acute liver injury in rats. We transfected immortalized but not tumorigenic rat
      fibroblasts (Rat-1) with an expression plasmid containing the human HGF cDNA and
      established several cell lines expressing HGF. The biological activity of HGF
      produced by these cell lines was confirmed by its mitogenic effect on rat
      hepatocytes in vitro. Either one of the high-HGF-producer cell lines or parental
      Rat-1 cell line was transplanted into a syngenic rat spleen. Twelve days after
      transplantation, each rat was intraperitoneally injected with CCl4 and sacrificed
      48 h after CCl4 injection. In rats with continuous HGF supply significantly lower
      serum glutamic-pyruvic transaminase (GPT) level was observed compared to its
      marked elevation in control rats and the degree of hepatocyte damage was slight
      on histological analysis. These results indicate that continuous HGF supply
      effectively inhibits CCl4-induced acute liver injury and may suggest the
      possibility that this system would be useful on various liver diseases.

PMID- 8573111
TI  - Differential transcription of the human spermidine/spermine N1-acetyltransferase
      (SSAT) gene in human lung carcinoma cells.
AB  - The expression of spermidine/spermine N1-acetyltransferase (SSAT), the rate
      limiting enzyme in the catabolism of polyamines, is highly regulated by a number
      of factors including the natural polyamines and their analogues. The phenotype
      specific cytotoxicity that occurs in response to a class of polyamine analogues,
      the diethylpolyamines, is associated with a phenotype-specific superinduction of
      SSAT in human non-small-cell lung carcinomas, whereas in non-responding cell
      types, including the small-cell lung carcinomas, the superinduction of SSAT does
      not occur. In this study, we have investigated the molecular basis of this
      phenotype-specific SSAT induction in human lung carcinoma cells in response to
      N1,N12-diethylspermine (BESpm). To facilitate the study of transcriptional
      regulation, we have cloned and characterized 11 kb of the human SSAT locus,
      including 3500 bp of the 5' promoter region. Nuclear run-on transcription studies
      suggest that the initial induction of SSAT results from an increase in the rate
      of gene transcription. Results from Northern blot analysis and ribonuclease
      protection assays indicate a differential expression of SSAT mRNA between the
      analogue-responsive H157 and non-responsive H82 cells. There is no detectable
      SSAT mRNA in H82 cells, even after a 24-h analogue treatment, whereas SSAT mRNA
      in H157 cells was detectable by Northern blot analysis and increased more than
      100-fold following drug exposure. Furthermore, nuclear run-on transcription
      assays do not detect any active transcription of SSAT gene in either treated or
      untreated H82 cells. These results indicate that at least one component of the
      phenotype-specific induction of SSAT appears to be due to differences in
      transcriptional regulation of the gene. In addition, mapping of DNase I
      hypersensitive sites of the SSAT gene suggest that the cell type-specific
      promoter/enhancer utilization may control the expression of the SSAT gene in
      differentially sensitive cell types in vivo.

PMID- 8573113
TI  - Expression of multiple c-kit receptor messenger ribonucleic acid transcripts
      during postnatal development of the rat testis.
AB  - The c-kit protooncogene is a transmembrane tyrosine kinase receptor expressed
      during gametogenesis. Using the polymerase chain reaction (PCR), we have
      identified the c-kit receptor mRNA transcripts in the rat testis and studied
      their expression during postnatal development of the testis. Five different
      transcripts were identified using sets of primers encoding within the
      extracellular domain. Two transcripts were obtained from primer sets encoding
      regions within the cytoplasmic domain and the primer set encoding the entire
      length of the c-kit receptor. We have compared the levels of expression of these
      transcripts on different days during postnatal development. The level of
      expression of a particular transcript varied depending upon the developmental
      stage of the testis. In summary, our results suggest that multiple forms of mRNAs
      exist for the c-kit receptor in the rat testis, and they are regulated
      differentially during postnatal development.

PMID- 8573114
TI  - Enzymatic synthesis of anandamide, an endogenous cannabinoid receptor ligand,
      through N-acylphosphatidylethanolamine pathway in testis: involvement of Ca(2+)
      dependent transacylase and phosphodiesterase activities.
AB  - Rat testis was shown to contain significant amounts of both N-acylethanolamine,
      including N-arachidonoylethanolamine (anandamide), and N
      acylphosphatidylethanolamine (N-acylPE), including N-arachidonoylPE. The fatty
      acid profiles of the N-acyl moieties of the two classes resembled each other. We
      confirmed that testis microsomes contain a phosphodiesterase activity catalyzing
      the release of anandamide from N-arachidonoylPE. They also contain an enzyme
      activity catalyzing the transfer of arachidonic acid from the 1-position of
      diacylphospholipids to PE to form N-arachidonoylPE. These results suggest that
      the N-acylPE pathway is important in the synthesis of anandamide in this tissue.

PMID- 8573115
TI  - Human anti-mitochondria autoantibodies appearing in iproniazid-induced
      immunoallergic hepatitis recognize human liver monoamine oxidase B.
AB  - Anti-mitochondria (anti-M6) autoantibodies have been found in the serum of
      patients with immunoallergic iproniazid (Marsilid)-induced hepatitis, but to date
      the identity of the protein antigen has not been determined. Here we show, using
      immunoprecipitation of pargyline-labelled proteins, that among the mitochondrial
      proteins, liver MAO-B is specifically recognized by the sera containing anti-M6
      antibodies. Moreover the enzymatic activity of MAO-B towards phenylethylamine and
      tyramine is also suppressed after this immunoprecipitation, contrary to the MAO-A
      activity towards 5-hydroxy-tryptamine. As MAO is irreversibly inhibited by
      iproniazid, these results suggest that the mechanism of iproniazid-induced
      appearance of anti-M6 antibodies could be another example of the reactive
      metabolite/enzyme haptenization mechanism already proposed in the case of
      tienilic acid for the appearance of anti-organelle antibodies in a drug-induced
      hepatitis.

PMID- 8573116
TI  - A region of the filamentous phage phi Lf genome that can support autonomous
      replication and miniphage production.
AB  - A 2028-bp fragment from the RF DNA of phi Lf, a filamentous phage of Xanthomonas
      campestris pv. campestris, was maintained autonomously as a minireplicon. Upon
      superinfection of the cells harboring the minireplicon with phi Lf, transducing
      miniphage particles were released. The minireplicon contained an open reading
      frame (ORF346) able to encode a polypeptide of MW39144, which possessed consensus
      motifs found in the Rep proteins from various sources. These findings suggested
      ORF346 to be the gene encoding replication initiation protein, gene II (gII) of
      phi Lf. Upstream to ORF346 were sequences with potential to form hairpin
      structures and a sequence similar to the integration host factor (IHF) binding
      site, structures similar to the intergenic region (IR) of the Ff phages. A 15 bp
      AT-rich core for phi Lf integration was found 37 bp downstream to the IHF binding
      site.

PMID- 8573117
TI  - Profilin forms tetramers that bind to G-actin.
AB  - Profilin binds to G-actin and affects polymerization. However, regulation of
      profilin function is generally unknown and controversy exists regarding profilin
      effects on actin polymerization. Because protein-protein interactions are
      implicated in many cellular responses, human platelet profilin self-association
      and actin inter-action was examined. Silver stained SDS-PAGE of poly-l
      proline/sepharose 4B column purified profilin revealed the presence of profilin
      (14.8 kD) and extraneous higher bands (primarily 30 kD and 58.5 kD). Re
      electrophoretic analysis of gel electroelution purified profilin yielded
      predominantly 14.8 kD and 58.5 kD proteins. Rabbit IgG antibodies made against
      gel electroelution-purified profilin recognized all profilin sizes on
      immunoblots. Capillary electrophoresis of profilin in solution produced a single
      peak that resolved into three distinct peaks upon addition of reducing agent or
      high salt conditions. Further, G-actin did not bind to 14.8 kD profilin on
      immunoblot overlay assays, but surprisingly bound only to 58.5 kD profilin. The
      data indicate that monomeric profilin forms tetramers which are the relevant high
      affinity actin-binding form.

PMID- 8573118
TI  - Association of cyclin-dependent kinase-4 and cyclin D1 in neonatal beta cells
      after mitogenic stimulation by lysophosphatidic acid.
AB  - Neonatal pancreatic islet beta cells retain a mitogenic capacity in response to
      growth factors. In this study an increased incorporation of 5-bromo-2'
      deoxyuridine in response to oleoyl-lysophosphatidic acid is preceded by a GTP
      dependent increase in phosphorylation of the extracellular signal-related kinase,
      ERK1. The presence of cyclin-dependent kinase-4 and an association with a
      catalytic partner cyclin D1, a process by which the progression through the cell
      cycle is regulated in other cell types, was shown to follow this. The mechanisms
      linking ERK1 phosphorylation and activation of cell cycle progression are not
      known. Investigation of this process in neonatal beta cells may provide a common
      pathway for the early response to growth factors and the conditions required for
      an increase in beta cell mass by proliferation.

PMID- 8573119
TI  - Decrease in the linking number of plasmid DNA in dnaA mutants of Escherichia
      coli.
AB  - We made use of agarose gel electrophoresis in the presence of chloroquine to
      examine the linking number of plasmids in temperature-sensitive dnaA mutants,
      including dnaA5 and dnaA46 mutants. The linking number of DNA prepared from dnaA
      mutants growing at 37 degrees C was lower than that from wild type cells yet
      there was no significant difference when cells were grown at 28 degrees C.
      Complementation analysis with a plasmid containing the wild type dnaA gene and
      phage P1-mediated transduction confirmed that mutations in the dnaA gene were
      responsible for the decrease in the linking number of DNA.

PMID- 8573120
TI  - Regulation of single Cl- channel conductance by insulin and tyrosine phosphatase.
AB  - The apical membrane of distal nephron epithelium (A6) had a Ca(2+)-activated
      outwardly rectifying Cl- channel with single-channel conductances of 3 pS for
      outward current and 0.8 pS for inward current. The single-channel conductance for
      inward current was dependent on cytosolic Ca2+ concentration. Insulin increased
      the single-channel conductance for the inward current by increasing Ca2+
      sensitivity about 300-fold. The insulin action was diminished by vanadyl
      hydroperoxide (vanadate, an inhibitor of protein tyrosine phosphatase (PTP)).
      Application of protein tyrosine kinase, p60c-src, reversibly diminished the
      insulin-induced increase in single-channel conductance. Further, the application
      of PTP to the cytosolic surface of the inside-out patch membrane, like insulin,
      increased single-channel conductance. PTP-mediated dephosphorylation of the
      phospho-tyrosine of the channel protein, as a mechanism of intracellular
      signaling of insulin action, is a novel mechanism for regulating single-channel
      conductance by modulating Ca2+ sensitivity.

PMID- 8573121
TI  - Inhibition of NF-kappa B activation in human T-cell lines by
      anetholdithiolthione.
AB  - Nuclear factor (NF)-kappa B is a redox sensitive cytosolic transcription factor.
      Redox regulation of NF-kappa B has been implicated in the activation of the human
      immuno-deficiency virus (HIV). Therefore, inhibition of NF-kappa B activation may
      be an effective strategy for acquired immunodeficiency syndrome therapy.
      Anetholdithiolthione (ADT, 5-[p-methoxyphenyl]-3H-1,2-dithiol-3-thione) is an
      antioxidant which has been used to protect against acetaminophen- and CCl4
      induced hepatotoxicity, lipid peroxidation, radiation injury, and also has been
      used clinically as an anti-choleretic agent. The present study examined the
      effect of ADT pretreatment on NF-kappa B activation in response to a variety of
      stimuli such as H2O2, phorbol myristate acetate (PMA) or tumor necrosis factor
      alpha (TNF alpha). PMA and TNF alpha induced activation of (NF)-kappa B in human
      Jurkat T-cells was partially inhibited by ADT (0.1 mM) pretreatment. ADT (0.1 mM)
      also inhibited H2O2 induced activation of the transcription factor in the
      peroxide sensitive human Wurzburg T-cells. Furthermore, ADT treated Wurzburg
      cells had significantly higher glutathione levels as compared with untreated
      cells. H2O2 induced lipid peroxidation in Wurzburg cells was remarkably inhibited
      by ADT pretreatment. ADT, a pro-glutathione antioxidant, was observed to be
      capable of modulating NF-kappa B activation.

PMID- 8573122
TI  - Dexamethasone inhibits insulin binding to insulin-degrading enzyme and cytosolic
      insulin-binding protein p82.
AB  - We recently demonstrated that insulin specifically binds to several cytosolic
      insulin-binding proteins (CIBPs) including insulin-degrading enzyme (IDE) and
      CIBP p82 in cytosol isolated from H35 rat hepatoma cells. Insulin binding to
      these CIBPs was regulated by culture conditions, such as serum or insulin. In the
      present study, we examined the effect of dexamethasone on insulin binding to
      CIBPs in H35 cells. When the cells were treated with 100 nM dexamethasone for 24
      hrs, insulin binding to IDE and CIBP p82 was decreased by about 50% without
      decreasing the expression level of IDE. Insulin added with the dexamethasone
      prevented the steroid's effect. Furthermore, dexamethasone directly blocked
      insulin binding to CIBPs in isolated cytosol. These results suggest that
      dexamethasone, directly or as a complex with other proteins, binds to IDE and
      CIBP p82 and changes their ability to bind insulin, possibly by inducing a
      conformational change or by blocking insulin binding sites. IDE was recently
      identified as a receptor accessory factor for androgen and glucocorticoid
      receptors and plays an important role in the regulation of gene transcriptional
      responses. Combined with previous reports, our findings suggest IDE and other
      CIBPs such as CIBP p82 may play a role in the cross-talk between insulin and the
      signal transduction pathways of steroid hormones.

PMID- 8573124
TI  - In vivo antitumor effect of cytotoxic T lymphocytes engineered to produce
      interferon-gamma by adenovirus-mediated genetic transduction.
AB  - Immunotherapy with adoptive transfer of genetically-modified cytotoxic T
      lymphocytes (CTL) is a promising approach for cancer gene therapy. We developed
      an adoptive therapy model with murine tumor-specific CTL, to which very efficient
      (up to 100%) gene introduction was achieved by using recombinant adenoviral
      vectors. Through a comparative study on the antitumor effects of CTL genetically
      modified with cytokine genes, transduction with interferon-gamma gene resulted in
      a prominent increase in therapeutic efficacy of CTL in both metastatic and
      subcutaneous tumor models. Further additive effect was obtained by the adoptive
      cellular therapy in combination with vaccination of cytokine gene-modified tumor
      cells. Our findings provide a hopeful strategy of adoptive immunotherapy for
      human cancers.

PMID- 8573123
TI  - Islet fructose 6-phosphate, 2-kinase:fructose 2,6-bisphosphatase: isozymic form,
      expression, and characterization.
AB  - Polymerase chain reaction analysis of the mRNA isolated from rat islets
      demonstrated that the major isozyme of Fructose 6-P,2-kinase:Fructose 2,6
      bisphosphatase was the heart type enzyme, and that the liver type enzyme was not
      detectable. The islet enzyme was expressed in Escherichia coli and purified to
      homogeneity. The islet enzyme showed the highest Fructose 6-P,2-kinase activity
      (478 milliunits/mg) compared to the other isozymes and Fructose 2,6-Pase activity
      (39 milliunits/mg). Fructose 6-P,2-kinase showed KmF6P = 17 microM, which is
      within the range of in vivo Fru 6-P concentrations in islets. 6-P-Gluconate was a
      potent inhibitor of Fructose 2,6-Pase. The data suggest that Fructose 6-P,2
      kinase activity of the bifunctional enzyme was high and Fructose 2,6-Pase
      activity was inhibited under physiological variations of blood glucose
      concentration.

PMID- 8573125
TI  - Physical structure and expression of alkBA encoding alkane hydroxylase and
      rubredoxin reductase from Pseudomonas maltophilia.
AB  - The structural genes of the Pseudomonas maltophilia alk system, which are
      localized on the OCT plasmid were cloned as a 4.2-kilobase pair Hind III
      fragment. This fragment contains sequences for alkane hydroxylase gene (alkB) and
      rubredoxin reductase gene (alkA), respectively. The alkB gene encodes a 373-amino
      acid polypeptide (47.4 kD) that can be expressed at high levels in Pseudomonas
      and Escherichia coli. The alkBA genes were complemented with alkane hydroxylation
      in both bacteria. This result shows that alkBA gene is essential for alkane
      hydroxylation since chromosomal loci have been encoded for other enzymes involved
      in fatty acid oxidation.

PMID- 8573126
TI  - Agouti protein inhibits growth of B16 melanoma cells in vitro by acting through
      melanocortin receptors.
AB  - Agouti protein is known to antagonize cAMP formation, tyrosinase activation and
      melanogenesis in mouse B16-F1 melanoma cells induced by alpha-melanocyte
      stimulating hormone (alpha-MSH). We now demonstrate that although agouti binds to
      the melanocortin receptor MC1-R with an almost identical affinity to that of
      alpha-MSH, it does not antagonize the inhibitory action of alpha-MSH on the
      growth of B16-F1 cells. Instead it has a similar antiproliferative action with a
      half-maximal effective concentration of 13 nM. In G4F cells lacking MC1-R, agouti
      is without effect. Agouti was also found to induce MC1-R down-regulation with
      identical kinetics and magnitude as alpha-MSH. Thus, the different effects of
      agouti on B16-F1 cells proceed via interaction with MC1-R but are not exclusively
      antagonistic.

PMID- 8573127
TI  - Role of the purinergic P2Z receptor in spontaneous cell death in J774 macrophage
      cultures.
AB  - J774 mouse macrophages express an ionotropic receptor gated by extracellular ATP.
      Activation of this receptor, currently named purinergic P2Z, causes transmembrane
      ion fluxes, plasma membrane depolarization, cell swelling and eventual cell
      death. The physiological role of this receptor is as yet unknown. In the present
      report we show that macrophage cell clones that hypo-express the P2Z receptor
      showed a very low degree of spontaneous cell death in culture, while hyper
      expressing clones were exceedingly susceptible to cell death. To further support
      a role for ATP receptors in spontaneous cell death, addition to the macrophage
      cell cultures of oxidized ATP, a selective inhibitor of ionotropic purinergic
      receptors, or the ATP-hydrolysing enzyme apyrase, also reduced spontaneous death.

PMID- 8573128
TI  - Stimulation of nuclear polyphosphoinositide synthesis by GTP-gamma-S: a potential
      regulatory role for nuclear GTP-binding proteins.
AB  - The nonhydrolyzable GTP analogue GTP-gamma-S was capable of stimulating in vitro
      phosphorylation of polyphosphoinositides in isolated nuclei prepared from mouse
      erythroleukemia cells. On the contrary, GDP-beta-S was ineffective. The
      stimulation was not detectable when nuclei were prepared from erythroleukemia
      cells induced to differentiate by exposure to dimethyl sulfoxide. Both nuclear
      phosphomonoesterase and phospholipase C activities were not influenced by GTP
      gamma-S. Our results point to the likelihood that nuclear phosphoinositide
      kinases might be regulated by a GTP-binding protein.

PMID- 8573129
TI  - Significance and immunoassay of 9- and 13-hydroxyoctadecadienoic acids.
AB  - Linoleic acid, the predominant polyunsaturated fatty acid in the diet, can be
      metabolized by cyclooxygenase, lipoxygenase and P450 enzymes. The monohydroxy
      lipoxygenation products of linoleic acid, 9- and 13-hydroxyoctadecadienoic acids
      (9(S)- and 13(S)-HODEs), are the most widely distributed of the known linoleic
      acid metabolites. These compounds exhibit interesting biological activities,
      including regulation of platelet function, maintenance of vascular
      thromboresistance and transduction of the cellular responses to certain growth
      factors. In view of their biological significance, we have produced polyclonal
      antibodies for the first time to these bioactive lipids to develop an easy,
      inexpensive, sensitive, specific and rapid enzyme immunoassay method for these
      bioactive lipids.

PMID- 8573130
TI  - Expression of HIV-1 envelope glycoprotein alters cellular calmodulin.
AB  - Removal of parts of a known calmodulin binding site at the C-terminus of HIV-1
      envelope glycoprotein, gp160, can result in diminished infectivity. We
      investigated whether expression of full length gp160 would result in changes in
      intracellular calmodulin compared to expression of gp160 truncated to remove both
      known calmodulin binding sites. Both Western and Northern blots demonstrated that
      expression of gp160 led to increased calmodulin when compared to expression of
      truncated gp160. The induced calmodulin was associated preferentially with a
      particulate subcellular fraction. Confocal immunomicroscopy confirmed the
      increase in calmodulin and also showed that there was enhanced colocalization of
      calmodulin with gp160. Understanding of the role of calmodulin in the viral life
      cycle may lead to new therapeutics.

PMID- 8573131
TI  - Early regionalized expression of a novel Xenopus fibroblast growth factor
      receptor in neuroepithelium.
AB  - A cDNA encoding a novel Xenopus fibroblast growth factor receptor, XFGFR4B, has
      been cloned. XFGFR4B mRNA is detected throughout embryogenesis. However, from the
      late gastrula stage on, XFGFR4B transcripts are expressed in two defined areas of
      the anterior neural plate. Interestingly, these two regions are fated to become
      parts of the retina, midbrain, hindbrain, and otic vesicle, all of which continue
      to express XFGFR4B mRNA in tailbud stage embryos and early tadpoles. Expression
      of XFGFR4B mRNA can be maintained at neurula stage in isolated blastula ectoderm
      in response to mesodermal induction by activin or neural induction by noggin,
      suggesting that XFGFR4B expression might be regulated by early cell interactions.
      Distribution of XFGFR4B mRNA suggests that XFGFR4B might serve an important
      function during patterning of neuroepithelium.

PMID- 8573132
TI  - Role of a truncated erythropoietin receptor for erythroid differentiation.
AB  - Erythropoietin (EPO) is a cytokine that regulates erythropoiesis through the EPO
      receptor (EPOR). We reported previously that erythroid progenitor cells express
      both a full-length and a truncated form of EPOR (EPOR-F and EPOR-Tph). EPOR-Tph
      cannot transmit growth signals and acts as a dominant negative regulator against
      EPOR-F-mediated signals for cell survival and growth. Upon transfection of EPOR-F
      in a cell line, Ba/F3, beta-globin accumulation, which is considered to be a
      marker of erythroid-differentiation, is inducible in the transformants. We show
      here that the co-expression of EPOR-Tph in EPOR-F-transformants does not inhibit
      and rather upregulates the beta-globin induction while inhibiting survival and
      growth of the transformants. These data suggest that, in contrast to survival and
      growth signals, EPOR-Tph acts as a positive regulator for erythroid
      differentiation signals in erythroid progenitor cells.

PMID- 8573133
TI  - Identification of the S-Endo 1 endothelial-associated antigen.
AB  - We have recently described a monoclonal antibody, S-Endo 1, recognizing a
      molecule constitutively expressed in all types of human endothelial cells. We
      showed that this protein around 118 kDa and located at the endothelial cell-cell
      junction presented sequence identity with MUC18 described as a tumor marker in
      human melanoma. The difference in antibodies immunoreactivity and antigen
      molecular weight heterogeneity observed between various cell types strongly
      suggested S-Endo 1 antigen isoforms expression.

PMID- 8573134
TI  - In vivo inhibition of hepatitis B virus gene expression by antisense
      phosphorothioate oligonucleotides.
AB  - While an important goal of treatment for hepatitis B is to prevent the
      development of hepatocellular carcinoma, there has been no effective therapy for
      it. Antisense oligodeoxynucleotide treatment could in principle inhibit hepatitis
      B virus gene expression and suppress tumor development. We used a mouse model for
      hepatocellular carcinoma, which is transgenic for the hepatitis B virus HBx gene,
      to study antisense phosphorothioate oligodeoxynucleotides. Among 2 series of
      sense and antisense oligodeoxynucleotides, only antisense sequences covering the
      initiation codon of the HBx gene effectively inhibited the expression of the HBx
      gene in the liver. Intraperitoneal injection of this antisense
      oligodeoxynucleotide thrice a week for 8 weeks resulted in the prevention of
      preneoplastic lesion development in the liver without inflammation in the liver
      or developmental disturbance of the mice. Antisense phosphorothioate
      oligodeoxynucleotides can inhibit the expression of a hepatitis B virus gene and
      may be a promising method for the prevention of hepatocellular carcinoma in
      hepatitis B virus infection.

PMID- 8573135
TI  - Ca(2+)-dependent protease I from Allomyces arbuscula.
AB  - A monomeric Ca(2+)-dependent protease (CDP I) of 39 kDa active at neutral pH has
      been purified from the aquatic fungus Allomyces arbuscula. The enzyme elutes at
      NaCl molarity of 0.07 M from the DEAE (DE52)-cellulose columns in contrast to the
      second Ca(2+)-dependent protease (CDP II) characterized earlier which elutes at
      0.18 M NaCl. The enzyme has no basal activity in the absence of Ca2+ and requires
      1.7 mM Ca2+ for half maximum activation of the in vitro enzyme activity. The
      enzyme prefers substrates with Arg in P1 position but this specificity also
      depends strongly on the nature of the subsite residues, for example Pro in P2
      position. The enzyme is glycosylated and contains essential cysteine residues in
      the active site. It appears to be an atypical cysteine protease as it is
      inactivated to varying degree with some serine protease inhibitors.

PMID- 8573136
TI  - Activation of the proteasome during Xenopus egg activation implies a link between
      proteasome activation and intracellular calcium release.
AB  - Ubiquitin-dependent proteolysis is required for cell cycle progression. Here, we
      demonstrate that the proteasome is activated during in vivo Xenopus egg
      activation, induced by treatment with the calcium ionophore A23187. It was found
      that activation is due to the calcium-induced assembly of the 26 S proteasome
      from the 20 S proteasome. We propose that proteasome activation is regulated by
      cell cycle calcium transients, which are controlled upstream by an endogenous
      cell cycle oscillator that is independent of the cyclin-dependent kinase cycle.

PMID- 8573137
TI  - Hepatocyte growth factor-induced proliferation of primary hepatocytes is mediated
      by activation of phosphatidylinositol 3-kinase.
AB  - Primary hepatocytes respond to the proliferating signals of Hepatocyte Growth
      Factor (HGF) through activation of the tyrosine kinase activity of the met (p145)
      receptor. Addition of dHGF in hepatocyte cultures resulted in receptor
      phosphorylation which co-precipitated with a phosphorylated protein of 85 kDa.
      This protein was identified as the regulatory subunit of phosphatidylinositol 3
      kinase (PI 3-kinase). Co-precipitation of the PI 3-kinase regulatory subunit with
      the met receptor was observed only with the phosphorylated receptor. Wortmanin,
      which specifically inhibits PI 3-kinase, was found to abolish the hepatocyte DNA
      synthetic response due to stimulation with dHGF. It is suggested that the D-3
      phosphorylated inositol phospholipids participate as major regulators in the
      growth and differentiation factor-initiated cascades, this not being restricted
      to primary hepatocytes.

PMID- 8573138
TI  - The pleiotropic effect of the GTS1 gene product on heat tolerance, sporulation
      and the life span of Saccharomyces cerevisiae.
AB  - We investigated whether or not the potential clock gene, GTS1, of the yeast
      Saccharomyces cerevisiae, shows pleiotropic effects on the yeast cellular
      processes. We tested the efect of the Gts1 protein on heat tolerance, sporulation
      and life-span, by characterizing the phenotypes of transformants with different
      copy numbers of the gene. We found that the Gts1 protein affects the capacity of
      heat tolerance in the stationary phase and the speed leading to sporulation in a
      gene-dose dependent manner, and that both inactivation and overexpression of the
      gene shortened the life-span of yeast. These results supported the notion that
      GTS1 affects the biological clock of the yeast S. cerevisiae, although this
      cannot be definitively concluded because the strain cannot be synchronized with
      circadian or ultradian rhythms.

PMID- 8573139
TI  - Intracellular generation of amyloid beta-protein from amyloid beta-protein
      precursor fragment by direct cleavage with beta- and gamma-secretase.
AB  - Two amyloid beta protein precursor (beta APP) fragments involving Met and 103
      amino acids of C-terminus of beta APP (delta NOR-beta) and its KM-NL substitution
      (delta NL-beta) were expressed in COS-7 cells to clarify the proteolytic
      cleavages to generate amyloid beta protein (A beta). The 4.5-kD protein, A beta
      with additional N-terminal amino acids, and 4-kD A beta were directly produced
      and released from 12.5-kD expression proteins without any production of 11.4-kD C
      terminal fragment starting at N-terminus of A beta and 3-kD "p3" A beta
      derivative. Intracellular 4-kD A beta was also detected. The substitution of KM
      NL of beta APP found in Swedish familial Alzheimer's disease (AD) promoted the
      production of intracellular A beta and its release with no increase in level of
      11.4-kD C-terminal fragment. These results suggested the presence of a distinct
      pathway in which A beta is directly cleaved at both N- and C-termini from beta
      APP fragment intracellularly to release A beta. Since KM-NL substitution enhanced
      intracellular A beta generation, this pathway may be associated with
      amyloidogenesis in AD.

PMID- 8573140
TI  - Activation of bovine photoreceptor guanylate cyclase by S100 proteins.
AB  - S100 proteins are acidic calcium-binding proteins present in high concentration
      in the brain and at lower concentrations in peripheral tissues. Their function
      remains to be elucidated in many tissues. In this report we show for the first
      time that S100 proteins stimulate the bovine photoreceptor membrane guanylate
      cyclase. The extent of stimulation varied between the different S100 proteins
      with the S100b exhibiting the highest level of influence. The stimulation by all
      S100 proteins was calcium dependent, with the half-maximal stimulation occurring
      at about 35-40 microM calcium. These results suggest that in some cells S100
      proteins can mediate calcium signals via cyclic GMP.

PMID- 8573141
TI  - Molecular cloning and sequence analysis of the porcine insulin-like growth factor
      binding protein-5 complementary deoxyribonucleic acid.
AB  - We report here for the first time the isolation of a cDNA clone containing the
      open reading frame sequence for porcine insulin-like growth factor binding
      protein-5 (pIGFBP-5) and the complete deduced amino acid sequence for this
      porcine IGFBP. The cDNA sequence shares 94%, 90% and 91% identity to its human,
      mouse and rat counterparts, respectively. The deduced amino acid sequence
      consists of 252 amino acids and a putative 19 amino acid signal and shares 97%,
      96%, and 96% identity to the human, mouse and rat peptides, respectively. The
      mature peptide contains the 18 conserved cysteines found in all of the IGFBPs.
      Northern blot analysis of total RNA isolated from porcine heart, muscle and
      spleen using a 315 base pair cDNA insert derived from the pIGFBP-5 open reading
      frame sequence revealed a single mRNA transcript of 6.0 kilobases.

PMID- 8573142
TI  - Analysis of p16INK4a and its interaction with CDK4.
AB  - The interaction between cyclin-dependent kinase 4 (CDK4) and its inhibitor
      p16INK4a (p16) was studied by random mutagenesis and yeast two-hybrid system. The
      gene encoding p16 was mutagenized randomly and the amino acid changes that affect
      the binding of p16 to CDK4 were identified. Several amino acid residues were
      shown to be important for the binding and many of these changes occur at residues
      conserved in all known human p16 family proteins Most of the mutant p16 proteins
      that failed to bind to CDK4 contained multiple amino acid changes, and these
      alterations were observed throughout the entire gene with no apparent mutational
      patterns or hot spots. Some of the mutations that moderately reduced the binding
      activity severely affected the kinase-inhibitory activity of p16.

PMID- 8573143
TI  - Expression of the carbohydrate recognition domain of bovine conglutinin and
      demonstration of its binding to iC3b and yeast mannan.
AB  - Bovine conglutinin is a collagenous C-type lectin (collectin) that is found in
      bovine serum. A recombinant protein, composed of the neck-region and the
      carbohydrate binding domain of bovine conglutinin, has been overexpressed in E.
      coli. The recombinant protein has been successfully renatured and showed the same
      sugar binding specificity as the native protein and was able to bind to yeast
      mannan and complement-activated immune complexes. The binding was calcium
      dependent and was inhibited by N-acetylglucosamine. The concentration of N
      acetylglucosamine required for 50% inhibition of binding to mannan was 1.77 mM
      for recombinant conglutinin and 0.71 mM for native conglutinin, respectively. The
      recombinant conglutinin should be useful in the assay and purification of
      circulating immune complexes and for therapeutic purposes involving the removal
      of immune complexes from patient's plasma.

PMID- 8573144
TI  - C-Fos is not essential for apoptosis.
AB  - The transcription factor AP-1, made up of dimers of Fos and Jun proto-oncogene
      products, is involved in distinct cellular processes, including cell
      proliferation, differentiation and apoptosis. In this study, we have used mice in
      which both copies of the c-fos gene were disrupted by targeted mutagenesis in
      order to analyze how the apoptotic response was affected in these mice. We
      prepared primary cultures from the lymphoid organs, spleen and thymus, obtained
      from both wild-type and c-fos -/- mice and analyzed the induction of apoptosis in
      these cultures in the absence and presence of etoposide, an inducer of apoptosis
      in distinct cell types. Primary cultures from both organs, spleen and thymus,
      isolated from wild-type mice underwent apoptosis after 3 and 6 h of culture,
      respectively. Addition of etoposide enhanced the apoptotic response and c-fos
      mRNA levels in both spleen and thymic cells. Nevertheless, we found that
      induction of apoptosis in primary cultures of cells obtained from spleen and
      thymus of c-Fos-deficient mice was practically identical to that observed in wild
      type mice. These results demonstrate that c-Fos is not essential for apoptosis
      and that cells lacking c-Fos may undergo normal apoptosis.

PMID- 8573145
TI  - Disruption of the GTP-cyclohydrolase I gene in Saccharomyces cerevisiae.
AB  - GTP-cyclohydrolase I is the first enzyme in the biosynthetic pathway leading to
      folic acid and tetrahydrobiopterin. We determined the complete sequence of the
      GTP-cyclohydrolase I gene from the yeast Saccharomyces cerevisiae. The gene,
      which is located in the subtelomeric region of the right arm of chromosome VII,
      gives a major transcript of about 1000 nt and encodes a protein of 243 amino
      acids, which is highly homologous to the GTP-cyclohydrolase I from bacteria to
      man. We obtained by gene replacement a knock-out mutant that shows a recessive
      conditional lethality due to folinic acid auxotrophy, and lacks any detectable
      specific enzymatic activity. The gene was identified as FOL2, previously
      genetically mapped in the same region (J. Game, personal communication).

PMID- 8573146
TI  - Fas antigen expression on synovial cells was down-regulated by interleukin 1
      beta.
AB  - Recent reports revealed that Fas antigen is functionally expressed on human
      synovial cells and apoptosis can be induced in these cells by anti-Fas antibody.
      We examined the effect of interleukin 1 beta (IL-1 beta) on Fas antigen-mediated
      apoptosis on human synovial cells in vitro. Using flowcytometric analysis, IL-1
      beta inhibited Fas antigen expression on synovial cells in a dose-dependent
      fashion. No significant difference of Fas antigen gene expression between IL-1
      beta-treated and untreated synovial cells was observed by RT-PCR analysis,
      suggesting that the inhibitory effect of Fas antigen expression by IL-1 beta is
      at posttranscriptional level. Apoptosis of synovial cells was easily induced by
      treatment of these cells with anti-Fas antibody. In contrast, pretreatment of
      synovial cells with IL-1 beta protected these cells against Fas antigen-mediated
      apoptosis. The expression of bcl-2 on synovial cells, known to interfere with the
      apoptotic process mediated by the Fas antigen, was not influenced by IL-1 beta.
      Our results suggest that IL-1 beta inhibits Fas antigen-mediated apoptosis of
      synovial cells and may perpetuate the hyperplasia of the synovium in patients
      with rheumatoid arthritis.

PMID- 8573147
TI  - A novel ubiquitously distributed isoform of GIRK2 (GIRK2B) enhances GIRK1
      expression of the G-protein-gated K+ current in Xenopus oocytes.
AB  - We have isolated a novel variant form of GIRK2, designated GIRK2B, from mouse
      brain cDNA library. GIRK2B was much shorter than the first type of GIRK2
      (GIRK2A), but its amino acid sequence was identical to the corresponding part of
      GIRK2A except the C-terminal eight amino acid residues. When GIRK2B cRNA was co
      injected with GIRK1 and m2-receptor cRNAs to Xenopus oocytes, acetylcholine
      induction of the inwardly rectifying K+ current was enhanced dramatically. This
      suggests that GIRK2B can form a heteromultimeric G-protein-gated K+ channel with
      GIRK1. The reverse transcription polymerase chain reaction analysis showed that
      GIRK2B mRNA distributed much more broadly than GIRK1 mRNA. Therefore, GIRK2B
      might also play other unrecognized roles in various tissues than to form a K+
      channel with GIRK1.

PMID- 8573148
TI  - Complete nucleotide sequence, structural organization, and an alternatively
      spliced exon of mouse h1-calponin gene.
AB  - From a CC1.2 embryonic stem cell genomic library, we isolated and sequenced a
      10.4-kb DNA segment (GenBank/EMBL Data Bank accession number L49022) containing
      the entire gene encoding mouse h1-calponin, an actin-associated smooth muscle
      specific protein and a potential modulator of contraction. Sequence data revealed
      that there are seven exons and six introns in the h1-calponin gene. Determined by
      primer extension mapping of the RNA transcripts, the transcription of h1-calponin
      gene initiates at the same site in stomach, urinary bladder and pregnant uterus
      smooth muscles. The genomic organization suggests that the previously identified
      alpha- and beta-calponin isoforms are produced by splicing of exon 7 at two
      alternative acceptor sites. Isolation and structural characterization of the h1
      calponin gene provides information to further investigate the expression
      regulation of this smooth muscle-specific gene.

PMID- 8573149
TI  - Rapid changes in light-scattering in the prism of Torpedo electric organ slice
      associated with the production of postsynaptic potentials.
AB  - Using a bifurcated lightguide placed on the surface of a prism of the electric
      organ slice of Torpedo, the generation of postsynaptic potentials by direct
      stimulation was found to be associated with readily detectable, disphasic optical
      changes. The changes consisted of a decrease in light-scattering during the
      rising phase of the electric potential, followed by a prolonged increase in
      scattering. The effects of varying the calcium-ion concentration in the medium
      strongly support the view the replacement of transmitter molecules for bound Ca
      ions in the receptor proteins is at the base of these changes. The effects of
      synaptically active reagents on these optical signals were demonstrated.

PMID- 8573151
TI  - Adult alveolar type II cells lack cAMP and Ca(2+)-activated Cl-channels.
AB  - We investigated the presence of Ca(2+)-activated Cl-channels in adult rat
      alveolar type II (ATII) using patch-clamp techniques. Only one active channel
      each, with a single channel conductance of 50 pS and an opening probability (Po)
      of 0.76 was found among 130 successful cell-attached and 5 inside-out patches.
      Addition of CPT-cAMP into the bath (500 microM) induced one active patch from 33
      silent cell-attached patches. Incubation of 9 ATII cells, with ionomycin (1
      microM), failed to elicit chloride single currents in 9 cell-attached patches. Cl
      currents were also absent from 35 whole cell patches, even after the addition of
      10 microM terbutaline in the bath or 1 mM ATP and 5 mM MgCl2 in the pipette.
      These results indicate that only a very small fraction of adult rat ATII cells
      express CFTR and suggest that Cl- ions are passively transported across the cell
      junctions.

PMID- 8573150
TI  - Effects of phospholipase C inhibitors on Ca2+ channel stimulation and Ca2+
      release from intracellular stores evoked by alpha 1A- and alpha 2A-adrenoceptors
      in rat portal vein myocytes.
AB  - The ability of phospholipase C inhibitors to inhibit Ca2+ channel stimulation and
      Ca2+ release from intracellular stores evoked by norepinephrine in single rat
      portal vein myocytes was investigated in the aim of identifying the type of
      phospholipase C involved in the transduction pathways activated by alpha 1A- and
      alpha 2A-adrenoceptors. U73122 (an inhibitor of phosphatidylinositol
      phospholipase C) inhibited in a concentration-dependent manner the release of
      Ca2+ from the intracellular stores induced by activation of alpha 1A
      adrenoceptors and related to inositol phosphate production whereas U73343 was
      ineffective. Both compounds had no effect on the release of Ca2+ induced by
      caffeine. However, U73122 and U73343 inhibited the L-type Ca2+ channel. D609 (an
      inhibitor of phosphatidylcholine-phospholipase C) had no direct inhibitory
      effects on the L-type Ca2+ channel but it inhibited concentration dependently the
      alpha 2A-adrenoceptor-induced stimulation of Ca2+ channels, which had been shown
      to be independent of phosphatidylinositol hydrolysis. Therefore, these results
      suggest that alpha 2A-adrenoceptors activate a phosphatidylcholine-phospholipase
      C in vascular myocytes. However, D609 had other sites of action as it blocked
      norepinephrine- and caffeine-induced Ca2+ release from the intracellular stores.

PMID- 8573152
TI  - The occurrence of hsp70 in the outer membrane of plant mitochondria.
AB  - Hsp70 was localized to the mitochondrial outer membranes of bean and cauliflower
      mitochondria. Western blotting showed that the outer membrane hsp70 was
      antigenically distinct from the mitochondrial-matrix hsp70, but was similar to
      the cytosolic form. The protein was resistant to solubilization with 200 mM
      sodium carbonate which showed the hsp70 was tightly bound to the outer membrane.
      Proteinase K studies suggested that the hsp70 was partially exposed to the
      cytosol with approximately 17% of the protein protease-accessible. It is
      suggested that the position of the outer membrane hsp70 could relate to a
      precursor unfolding function during protein import into mitochondria.

PMID- 8573153
TI  - A novel ligand blot assay detects different hyaluronan-binding proteins in rat
      liver hepatocytes and sinusoidal endothelial cells.
AB  - We have developed a sensitive ligand blot assay to detect hyaluronan (HA) binding
      proteins in cell extracts using 125I-HA. Samples to be tested are electrophoresed
      using standard, nonreducing SDS-PAGE conditions, electro-transferred to
      nitrocellulose then blocked in buffer containing Tween 20. After incubation with
      125I-HA the nitrocellulose is washed and HA-binding proteins are detected by
      autoradiography. This method was used to detect different HA-binding proteins in
      isolated rat liver cell preparations. Two HA-binding bands of 175 kD and 350 kD
      were detected in sinusoidal endothelial cells. Both bands were competed virtually
      100% with nonlabeled HA. Using rat hepatocytes, the assay detected major bands at
      85 kD and 180 kD. In addition, histones present in both cell types were readily
      detected in the low MW region. Thus, two different liver cell types show
      different HA-binding patterns. The blocking procedure is critical for successful
      renaturation of HA-binding activity, since substitution of BSA for Tween 20 did
      not result in detectable 125I-HA-binding. This ligand blot assay will be a
      powerful tool to detect HA-binding proteins in various other tissues and cell
      types.

PMID- 8573154
TI  - Enhanced galactosyltransferase expression in the failing hearts of spontaneously
      hypertensive rats.
AB  - To examine differences in cardiac gene expression between spontaneously
      hypertensive rats with and without heart failure, we have used subtractive
      hybridization to identify differentially expressed genes. After subtraction,
      cDNAs were amplified by PCR, cloned and sequenced. One of 36 independent cDNAs
      was found to be 86% homologous to murine UDP-galactose:N-acetylglucosamine beta
      1,4-galactosyltransferase. RNA blot analysis confirmed the approximately 4.0 kb
      rat galactosyltransferase transcript was increased in failing hearts relative to
      non-failing hearts. Biochemical assay also showed increased galactosyltransferase
      activity in the failing hearts.

PMID- 8573155
TI  - The human asialoglycoprotein receptor is palmitoylated and fatty deacylation
      causes inactivation of state 2 receptors.
AB  - We report here for the first time that ASGP-Rs expressed in the human hepatoma
      cell lines HuH-7 and HepG2 are fatty acylated. Cells were metabolically labeled
      with [3H]palmitate and active ASGP-Rs, which contain two subunits (HHL1 and
      HHL2), were purified by affinity chromatography and subjected to nonreducing SDS
      PAGE and fluorography. [3H]Palmitate was covalently incorporated into both HHL1
      and HHL2. When gel slices containing HHL1/HHL2 were treated at neutral pH with 1
      M hydroxylamine, but not 1 M Tris, > 95% of the radioactivity was removed,
      indicating that the attachment of palmitate to ASGP-Rs is to cysteines.
      Furthermore, the same mild hydroxylamine treatment caused partial ASGP-R
      inactivation; 50-70% of receptors corresponding to the previously characterized
      State 2 ASGP-Rs were inactivated. We conclude that both HHL1 and HHL2 are
      covalently modified by fatty acylation, which may regulate the ligand-binding
      activity of human State 2 ASGP-Rs. We propose that fatty acylation/deacylation of
      cytoplasmic domains is a general mechanism by which extracellular ligand-binding
      activity of oligomeric transmembrane receptors can be regulated.

PMID- 8573156
TI  - Inhibition of vanadate-induced astrocytic stress fiber formation by C3 ADP
      ribosyltransferase.
AB  - Mechanisms of vanadate-induced actin reorganization were examined in cultured
      astrocytes. Treatment of protoplasmic astrocytes with 0.5 mM dibutyryl cAMP
      (DBcAMP) caused the disappearance of stress fibers (SFs) and focal adhesions
      (FAs) accompanied with cellular stellation. A subsequent addition of 1 mM
      orthovanadate (VO4(3-) reorganized SFs and FAs in DBcAMP-treated cells. The newly
      formed FAs had increased phosphotyrosine levels. VO4(3-) reorganized SFs and FAs
      in stellate astrocytes induced by 5 microM cytochalasin B, 50 microM ML-9 and 20
      microM W-7. Cytoplasmic microinjection of 20 micrograms/ml C3 ADP
      ribosyltransferase of C. botulinum, which inactivates rho proteins, caused
      disappearance of SFs. The effect of C3 enzyme on SFs was not reversed by a
      subsequent addition of VO4(3-). These results suggest that rho proteins are
      involved in vanadate-induced reorganization of cytoskeletal actin.

PMID- 8573157
TI  - Molecular cloning of murine CC CKR-4 and high affinity binding of chemokines to
      murine and human CC CKR-4.
AB  - We have cloned the murine homologue of human CC Chemokine Receptor-4 (CC CKR-4).
      In equilibrium competition binding assays performed in undifferentiated HL-60
      cells transfected with human and murine CC CKR-4 cDNA, the IC50 values for the
      binding of [125I]macrophage inflammatory protein-1 alpha to human and murine CC
      CKR-4 were 14.5 +/- 9.0 nM and 10.1 +/- 3.0 nM, respectively, and the IC50 values
      for the binding of [125I]RANTES to human and murine CC CKR-4 were 9.3 +/- 3.0 nM
      and 5.7 +/- 2.6 nM, respectively. The cDNA clone for murine CC CKR-4 is 1531 bp,
      and the largest open reading frame encodes a protein of 360 amino acids that is
      85% identical to human CC CKR-4. Murine CC CKR-4 was detected in the thymus and T
      cell lines by Northern blot analysis. This first report of direct binding of
      chemokines to CC CKR-4 demonstrates that the highly homologous human and murine
      receptors have similar binding characteristics and tissue distribution.

PMID- 8573158
TI  - Protein tyrosine kinases and phosphatases control apoptosis induced by
      extracellular adenosine 5'-triphosphate.
AB  - Extracellular ATP (ATPo) induces apoptosis and osmotic lysis in several cell
      lines. We investigated the role of protein tyrosine kinases (PTKs) and
      phosphatases (PTPases) in ATPo-induced apoptosis. The PTK inhibitor genistein
      prevented DNA fragmentation due to ATPo without affecting cell lysis. Comparison
      of western blot analysis and in vitro kinase assays of anti-phosphotyrosine
      immunoprecipitates indicated that ATPo activated PTKs whose activity was tightly
      regulated by PTPases. In fact, an early increase in tyrosine kinase activity was
      observed after ATPo-treatment and was prevented by specific PTPase inhibitors. In
      addition, a rapid dephosphorylation of phosphotyrosyl residues on several
      proteins was detected in ATPo-treated cells. Accordingly, inhibitors of PTPases,
      but not of serine/threonine phosphatases, were as effective as PTK-inhibitors in
      blocking ATPo-mediated DNA fragmentation. We describe the early events occurring
      in ATPo-induced apoptosis and suggest a role for PTPases in cell death.

PMID- 8573159
TI  - Changes in the activity of nuclear protein kinase CK2 during rat liver
      regeneration.
AB  - Protein kinase CK2 has been found in two nuclear fractions obtained after
      treatment of purified rat liver nuclei with nucleases (S1 fraction) and
      subsequently with 1.6 M NaCl (S2 fraction). In both fractions three isoforms of
      the alpha subunit were identified. Two of them corresponded to the classical
      alpha and alpha' subunits, whereas the identity of the third one (alpha 3)
      remains unknown. In the S1 fraction two peaks of CK2 activity were detected at 6
      h (5.5 fold) and 24 h (1.9 fold) after partial hepatectomy, whereas no
      significant changes were found in the S2 fraction. At 6 h after laparatomy a much
      lower increase of CK2 in S1 fraction was also detected (2.5 fold). The increases
      in CK2 activity found at 6 h after hepatectomy or laparatomy were accompanied
      with rises in the amount of the alpha subunit.

PMID- 8573160
TI  - The Vpr protein of human immunodeficiency virus type 1 binds to nucleocapsid
      protein p7 in vitro.
AB  - The Vpr protein of human immunodeficiency virus type 1 (HIV-1) is incorporated
      into the virion by the Gag polyprotein precursor Pr55gag. The importance of the
      p6gag sequence at the C-terminal end of Pr55gag has a crucial role in Vpr
      incorporation. To identify the Gag sequences directly involved in Vpr binding, we
      compared the Vpr binding affinities of the 71 amino acid nucleocapsid protein p7,
      the C-terminal peptide (35-71) p7C and p6gag by affinity chromatography. p7 and
      p7C have the strongest Vpr binding activities compared to p6gag. These results
      suggest that the nucleocapsid protein and its C-terminal domain may be important
      for the incorporation of Vpr into the mature HIV-1 virion and the subsequent
      localisation of viral nucleic acid to the cell nucleus by Vpr.

PMID- 8573161
TI  - A novel expression system for Salmonella typhimurium allowing high production
      levels, product secretion and efficient recovery.
AB  - A novel expression system for heterologous production in Salmonella typhimurium,
      taking advantage of the promoter, signal sequence and two IgG-binding domains
      (ZZ) from staphylococcal protein A, has been investigated. The production of two
      different fusion proteins, ZZ-M3 and ZZ-M5, was characterized in terms of
      production levels, product localization (periplasma or culture medium) and
      product quality after affinity purification. High expression levels and efficient
      product secretion were obtained, making the system attractive for vaccine
      development. The potential use of S. typhimurium as host for heterologous
      production in biotechnology is discussed.

PMID- 8573162
TI  - Down-regulation of HCW9 mRNA in rat hepatocytes during chemical hypoxia involves
      both transcriptional and posttranscriptional mechanisms.
AB  - HCW9 cDNA encodes a rat protein with 95% homology to mouse phospholipase A2
      activating protein (PLAP). Its mRNA, which is substantially decreased in rat
      hepatocytes during chemical hypoxic injury, was found to be expressed in all rat
      tissues examined, including liver, heart, brain, spleen, lung, skeletal muscle,
      kidney, and testis. To elucidate the mechanisms responsible for this hypoxia
      induced down-regulation of HCW9 mRNA levels, the transcription rate and half-life
      of HCW9 mRNA were measured. Nuclear run-off assays revealed a 54-57% inhibition
      in the transcription rate of HCW9 gene during chemical hypoxic injury. The half
      life of HCW9 mRNA decreased from approximately 15 min under normoxic conditions
      to approximately 7 min during chemical hypoxic injury. These findings suggest
      that HCW9 expression in rat hepatocytes is regulated at both the transcriptional
      and posttranscriptional levels during chemical hypoxia.

PMID- 8573163
TI  - Identification of new lens protease(s) using peptide substrates having in vivo
      cleavage sites.
AB  - Bovine lens extracts were incubated in pH 7.5 buffer with succinylated
      VSREEKPSSAPSS, SGVDAGHS, GKPTSAPSS and GKHNERQD, the peptides having age
      dependent in vivo cleavage sites in bovine and human alpha A-crystallin. The
      reaction products were analyzed to identify the initial protease cleavage sites.
      The results showed that bovine lens extracts contain protease activity that can
      cleave. Thr-Ser, Ser-Ala, Ser-Ser bonds in test substrates which correspond to
      peptide bonds Ser168-Ser169, Ser169-Ala170, Ser172-Ser173 in bovine alpha A
      crystallin and Thr-Ser, Ser169-Ala170, Ser172-Ser173 in human alpha A-crystallin.
      In addition, the same extracts were also capable of hydrolyzing Asp-Ala and Asn
      Glu bonds corresponding to Asp151-Ala152 and Asn101-Glu102 in alpha A-crystallin
      from bovine and human lenses. The cleavage specificity of the newly discovered
      protease(s) suggests that the in vivo truncation of alpha A-crystallin reported
      earlier may be due to the action of proteases. The newly discovered lens
      protease(s) were resistant to inactivation by E-64 and DFP. However, prior
      treatment of the lens extracts with leupeptin and chymostatin resulted in partial
      loss of Asn-Glu hydrolytic activity. N-ethylmaleimide treatment completely
      abolished in the Asn-Glu hydrolyzing activity.

PMID- 8573165
TI  - Acylation of peptide hydroxyl groups with the Bolton-Hunter reagent.
AB  - Reaction of the decapeptide gonadotropin releasing hormone (GnRH) with the Bolton
      Hunter reagent produced a single major derivative. Mass spectrometric analysis of
      this derivative at M-Scan Corporation revealed that O-acylation of the Ser4
      hydroxyl had occurred. Formation of the O-acylated Ser4 derivative was dependent
      on the presence of the His2 residue in GnRH. Similar experiments with several
      unrelated peptides revealed that the Bolton-Hunter reagent will readily acylate
      hydroxyl groups on serine, tyrosine, and threonine side chains located two
      positions from a histidine residue (e.g., His-X-Ser). Such O-acylated peptides
      can be formed under mild reaction conditions and appear to be relatively stable.
      Recognition of this sequence-specific O-acylation can be critical when labeling
      peptides with the Bolton-Hunter reagent and when interpreting experiments in
      which such modified peptides are used.

PMID- 8573164
TI  - Effect of cystathionine ketimine on the stimulus coupled responses of neutrophils
      and their modulation by various protein kinase inhibitors.
AB  - Human peripheral blood polymorphonuclear leukocytes were perincubated with
      cystathionine and cystathionine metabolites found in the urine of the patients
      with cystathioninuria. Among the cystathionine metabolites, cystathionine
      ketimine significantly enhanced the N-formyl-methionyl-leucyl-phenylalanine
      induced superoxide generation, but cystathionine and cyclothionine did not
      enhance the superoxide generation. Cystathionine ketimine also enhanced
      superoxide generation induced by opsonized zymosan but not those induced by
      arachidonic acid and phorbol myristate acetate. Superoxide generation induced by
      cystathionine ketimine was inhibited by genistein, an inhibitor of tyrosine
      kinase, and was enhanced by 1-(5-isoquinoline-sulfonyl)-2-methyl-piperazine, an
      inhibitor of protein kinase C.

PMID- 8573166
TI  - Identification of regions in the human angiotensin II receptor type 1 responsible
      for Gi and Gq coupling by mutagenesis study.
AB  - Previous mutagenesis studies of angiotensin II (Ang II) receptor type 1 (AT1)
      have focused on determining the regions responsible for Gq coupling using the rat
      AT1 receptor. We created human AT1 receptor mutants, expressed them in COS-7
      cells, and identified the domains crucial for Gi coupling as well as for Gq
      coupling. Substitution of Asp125, Arg126, Tyr127, and Met134 by Gly, Gly, Ala,
      and Ala in the highly conserved sequence of the second intracellular loop in most
      G protein-coupled receptors provided a mutant AT1 receptor which lost the ability
      to couple to both Gq and Gi with no impairment in its binding to Ang II. A
      truncated mutant lacking the carboxyl terminal 50 residues was completely
      deficient in coupling to Gi, whereas it retained full ability to bind to Gq, in
      contrast to the rat AT1 receptor. These findings demonstrate that the cytoplasmic
      tail in the human AT1 receptor is the determinant of specific Gi coupling.

PMID- 8573167
TI  - PIPPin, a putative RNA-binding protein specifically expressed in the rat brain.
AB  - In looking for genes encoding RNA-binding factors, we prepared an expression
      library in lambda gt11, by cloning cDNAs corresponding to the polyadenylated
      fraction of RNA from rat brain at the embryonal day 18. The library was then
      screened by binding to a radioactive RNA, transcribed in vitro from a cDNA
      encoding the rat histone variant H3.3. Here we report some findings concerning a
      cDNA for a protein which contains two putative double stranded RNA-binding
      domains (dsBD). The corresponding message is specifically expressed in the brain.
      Moreover, Southern blot analysis showed that the gene is highly conserved from
      Drosophila melanogaster to man.

PMID- 8573169
TI  - Mitochondrial nitric oxide synthase: a ubiquitous regulator of oxidative
      phosphorylation?
AB  - In this article we demonstrate the immunocytochemical localization of nitric
      oxide synthase in mitochondria isolated from heart, skeletal muscle, and kidney,
      using a monoclonal antibody directed against the endothelial form of nitric oxide
      synthase. The possibility that mitochondrially located nitric oxide synthase is a
      ubiquitous regulator of mitochondrial oxidative phosphorylation in mammalian
      cells is discussed.

PMID- 8573168
TI  - Activation of two Cynops genes, fork head and sonic hedgehog, in animal cap
      explants.
AB  - We have isolated cDNAs of sonic hedgehog (shh) and fork head from Cynops
      (Japanese newt) embryo. Their expression was investigated in relation to mesoderm
      induction by activin and basic fibroblast growth factor (bFGF). Different from
      these homologs in Xenopus, they are activated not only by activin but also by
      bFGF in animal cap explants, showing a difference of animal pole cells in
      responsiveness to bFGF between Cynops and Xenopus. We also investigated the
      involvement of fork head in shh activation. The expression of shh was activated
      in animal caps which overexpressed either of two Xenopus fork head homologs,
      pintallavis/XFD-1 or XFKH-1/XFD-1', indicating that fork head up-regulates the
      transcription of shh in Cynops embryo.

PMID- 8573170
TI  - Efficient gene transfer into mammalian cells using fusogenic liposome.
AB  - Fusogenic liposome (FL) based on Sendai virus constitutes a unique system that
      delivers the content efficiently into animal cells in vitro and in vivo. In this
      study we characterized unilamellar FL as a gene transfer vector in comparison
      with cationic lipid (CL)-DNA complex. FL transferred genes efficiently into
      cultured cells even when incubated for as little as 10 min, while CL-DNA complex
      required at least 30 min to reach the same level of gene expression. FL was also
      much less cytotoxic than CL-DNA complex under the conditions that resulted in the
      same level of gene expression. In addition, FL maintained 70% of the transfection
      activity even in the presence of 40% fetal calf serum (FCS), while CL-DNA complex
      almost completely lost their activity in the presence of 5% FCS. Furthermore, we
      found that FL could introduce and express luciferase gene into mouse ascites
      tumor cells in vivo, but CL-DNA complex could not even at higher concentrations
      of DNA. We conclude that unilamellar FL is a unique and efficient nonviral vector
      for gene transfer in vitro and in vivo.

PMID- 8573171
TI  - A novel antimicrobial peptide from Bufo bufo gargarizans.
AB  - A potent and structurally novel antimicrobial peptide was isolated and
      characterized from the stomach tissue of Bufo bufo gargarizans, an Asian toad.
      The 39-amino acid peptide, named buforin I, was purified to homogeneity by
      heparin-affinity column and reverse-phase HPLC. The amino acid sequence of
      buforin I was identical in 37 of 39 amino-terminal residues of Xenopus histone
      H2A. The buforin I showed strong antimicrobial activities in vitro against a
      broad-spectrum of microorganisms and was found to be more potent than magainin 2.
      In addition, a 21-amino acid peptide, named buforin II, which was derived from
      buforin I, showed more potent antimicrobial activities than buforin I.

PMID- 8573172
TI  - Selection of a peptide with affinity for the tumor-associated TAG72 antigen from
      a phage-displayed library.
AB  - A hexapeptide phage library was used to select peptides with affinity for the
      tumor-associated TAG72 antigen. Twenty-one phage clones were selected after the
      third round of biopanning. Three phage clones with the same DNA insert of ARTLRF
      were found to bind more strongly to the TAG72 antigen than other phage clones and
      the wild-type phage. A synthetic decapeptide GAARTLRFGA with two conjunctive
      amino acid residues of the phage coat protein III on each side of the selected
      peptide was found to bind more strongly to the TAG72 antigen than to other
      antigens such as the mouse metallothionein. Furthermore, immunohistochemical
      studies revealed that this peptide displayed preferential binding to colonic
      adenocarcinomatous cells expressing the TAG72 antigen. Therefore, this anti-TAG72
      peptide may be useful in serving as the starting point with regard to further
      designing peptidomimetics as potential pharmaceuticals.

PMID- 8573173
TI  - GTP hydrolysis by human tissue transglutaminase homologue.
AB  - Human tissue transglutaminase homologue cDNA was expressed in E. coli to analyze
      the catalytic characteristics. The transglutaminase homologue was purified by
      immunoaffinity chromatography. Specificity of GTP binding by the homologue was
      demonstrated by photoaffinity labeling in the absence or presence of GTP-gamma-S.
      The homologue had GTPase activity with an apparent Km value of 1.8 microM,
      several-fold lower than the reported Km values for the native tissue
      transglutaminase. GTPase activity was inhibited by guanine nucleotides in order
      GTP-gamma-S > GDP > GMP. The higher GTPase activity of the homologue may be
      related to the signaling events function.

PMID- 8573174
TI  - Angiotensin converting enzyme inhibitor normalizes vascular natriuretic peptide
      type A receptor gene expression via bradykinin-dependent mechanism in
      hypertensive rats.
AB  - We previously demonstrated that angiotensin converting enzyme (ACE) inhibitor
      normalizes the up-regulated gene expression of vascular natriuretic peptide type
      A (NP-A) receptor in hypertensive rats. To elucidate the mechanism, we examined
      the effect of angiotensin II receptor (AT1) antagonist (TCV-116) and bradykinin
      receptor (B2) antagonist (Hoe 140) on the NP-A receptor mRNA level in the aorta
      of genetically hypertensive rats (SHR-SP/Izm) using ribonuclease protection
      assay. The effect of ACE inhibitor on the NP-A receptor mRNA level was completely
      abolished by a concomitant administration of Hoe 140, while TCV-116 did not show
      any significant effect on the NP-A receptor mRNA level. These results suggest
      that bradykinin plays an important role in the regulation of the vascular NP-A
      receptor gene expression.

PMID- 8573175
TI  - Phosphorylation of Rho GDI stabilizes the Rho A-Rho GDI complex in neutrophil
      cytosol.
AB  - The GDP dissociation inhibitor Rho GDI from bovine neutrophil cytosol was
      purified in association with prenylated Rho A. Upon treatment of this complex
      with alkaline phosphatase, the Rho A and Rho GDI components were released to
      their free forms. Following migration in 2D-PAGE and specific immunodetection,
      the shape of the spot of Rho GDI was found to depend markedly on whether Rho GDI
      subjected to electrophoresis was present in a Rho A-Rho GDI complex or in a free
      form. In the first case Rho GDI focused as an elongated spot between pI 5.2 and
      pI 4.6 whereas in the later case it focused at a pI of 5.0-5.2 as a round spot.
      Activation of neutrophils by anaphylatoxin C5a in a [32Pi] supplemented medium
      resulted in radiolabeling of Rho GDI. In vitro incubation of Rho GDI with a
      neutrophil homogenate in the presence of [gamma 32P] ATP led also to
      radiolabeling of Rho GDI. Taken together these results suggest that Rho GDI in
      the Rho A-Rho GDI complex is phosphorylated and that the stability of the complex
      depends on the phosphorylation state of Rho GDI.

PMID- 8573176
TI  - Structure and expression of the tenecin 3 gene in Tenebrio molitor.
AB  - A genomic DNA fragment encoding tenecin 3, an antifungal protein was cloned from
      the genomic DNA library of Tenebrio molitor. The DNA sequence analysis showed
      that the coding region is divided into two exons by an intron of 49 bp in the
      middle of the putative leader peptide coding region. Southern blot analysis
      suggests that the gene is present as a single copy. The transcription initiation
      site was determined by primer extension analysis and S1 mapping. The TATA box and
      CCAAT box sequences were found at -30, and -121, respectively, from the
      transcription initiation site. Tenecin 3 mRNA is abundantly expressed in larvae
      and adults, while little was detected in RNAs from pupae, suggesting that the
      expression of the tenecin 3 gene is developmentally regulated.

PMID- 8573177
TI  - GTP, a nonsubstrate of ATP citrate lyase, is a phosphodonor for the enzyme
      histidine autophosphorylation.
AB  - ATP citrate lyase (EC 4.3.1.8.) was shown to be a major phosphorylation protein
      of a fraction derived from Zajdela rat hepatoma by chromatography on heparin
      Ultrogel, after the incubation with [gamma-32P]ATP or [gamma-32P]GTP. Histidine
      was the only amino acid in the purified enzyme phosphorylated by [gamma-32P]ATP
      or [gamma-32P]GTP in the autocatalytic reaction which occurred apparently through
      an intramolecular mechanism regardless of a donor of phosphate. GTP inhibits the
      ATP-dependent autophosphorylation competitively despite its failure to replace
      ATP in the formation of acetyl-CoA catalyzed by this enzyme.

PMID- 8573178
TI  - P2 purinoceptor-operated potassium channel in rat cerebellar neurons.
AB  - P2 purinoceptor agonists produced whole-cell potassium currents in cerebellar
      neurons with the order of potency 2-methylthio ATP (2-MeSATP) > ADP > ATP >
      adenosine > alpha,beta- methylene ATP > AMP > UTP. In the outside-out patch clamp
      configuration, 2-MeSATP evoked single channel currents with two major classes of
      slope conductances without latency. The currents were blocked by a G-protein
      inhibitor, GDP beta S, although they were not affected by a phospholipase C
      inhibitor, a selective protein kinase C or A inhibitor. In contrast, a potent G
      protein activator, GTP gamma S, produced single channel currents with same
      conductances as those of the currents induced by 2-MeSATP. These provide an
      indication that the P2 purinoceptor-operated potassium channel is regulated by
      the beta gamma subunits of a G-protein.

PMID- 8573179
TI  - Glycated albumin promotes a generalized vasculopathy in the db/db mouse.
AB  - Increased protein glycation has been mechanistically linked to accelerated
      vascular pathobiology in diabetes. Because glycated albumin induces biosynthetic
      abnormalities in cultured aortic endothelial cells that resemble those associated
      with macrovascular disease, we sought evidence that increased glycated albumin is
      operative in the genesis of diabetic vasculopathy in vivo. Plasma concentrations
      of fibronectin, a sensitive marker of endothelial cell damage, were increased two
      fold in diabetic db/db mice compared with their nondiabetic db/m littermates.
      Treatment with monoclonal antibodies specifically reactive with albumin modified
      by Amadori glucose adducts normalized fibronectin in diabetic animals despite
      persistent hyperglycemia. These findings suggest that increased glycated albumin
      causally contributes to diabetic vasculopathy, and that blocking this influence
      ameliorates vascular damage.

PMID- 8573180
TI  - Characterization of a mutant GLUT4 lacking the N-glycosylation site: studies in
      transfected rat adipose cells.
AB  - GLUT4, the insulin-responsive glucose transporter expressed primarily in muscle
      and adipose tissue, contains a single N-glycosylation site. We characterized a
      mutant GLUT4 lacking the N-glycosylation site (Asn57-->Gln) in primary cultures
      of rat adipose cells. We transiently transfected cells with expression vectors
      for epitope-tagged GLUT4 containing either wild-type (GLUT4-HA) or mutant (GLN57
      HA) cDNA sequences. Expression of GLN57-HA in adipose cells was approximately 10
      fold lower than for GLUT4-HA even though mRNA levels for both recombinant
      transporters were comparable. Biosynthetic labeling studies showed markedly
      decreased incorporation of [35S]-methionine/cysteine into GLN57-HA relative to
      GLUT4-HA consistent with either a decreased synthetic rate or accelerated
      degradation of GLN57-HA. Interestingly, transient transfection of GLUT4-HA and
      GLN57-HA in COS-7 cells (which do not express endogenous GLUT4) resulted in
      comparable levels of protein expression for both transporters. Thus, in the
      physiologically relevant adipose cell, glycosylation of GLUT4 appears to play an
      important functional role.

PMID- 8573181
TI  - Stimulation of c-Jun kinase and mitogen-activated protein kinase by ischemia and
      reperfusion in the perfused rat heart.
AB  - Ischemia and reperfusion lead to the rapid induction of proto-oncogenes in the
      heart and subsequent induction of genes with cardioprotective functions. The
      activity of the transcription factors c-Jun and ATF-2 can be stimulated by
      activation of c-Jun amino-terminal kinase (JNK) in response to a variety of
      stresses. Here we show that ischemia and reperfusion led to the activation of JNK
      and also of the distantly-related mitogen activated protein kinase (MAPK).
      Activation of JNK, but not (MAPK), was abolished by removal of calcium from the
      perfusate immediately prior to ischemia. In contrast, infusion of the hydrogen
      peroxide scavenger catalase abolished activation of MAPK in response to ischemia
      and reperfusion, but activation of JNK was inhibited significantly by catalase
      only when superoxide dismutase was also present. Hydrogen peroxide infusion
      activated MAPK but not JNK, supporting a role for hydrogen peroxide produced
      during reperfusion in MAPK activation. We conclude that while ischemia and
      reperfusion activate both JNK and MAPK, the mechanisms of activation are
      different for the 2 kinases. Activation of these kinases is likely to contribute
      to altered gene expression in response to ischemia and reperfusion.

PMID- 8573182
TI  - Missense mutations associated with familial Alzheimer's disease in Sweden lead to
      the production of the amyloid peptide without internalization of its precursor.
AB  - Production of soluble amyloid peptide precursor (APP) and amyloid peptide (A
      beta) was measured in CHO cells transfected by the wild-type APP 695 cDNA
      sequence or by the same sequence carrying missense mutations associated with
      familial Alzheimer's disease in Sweden. Deletion of the C-terminal domain of the
      protein corresponding to residues 654 to 695 of APP 695 not only inhibited very
      significantly the internalization of APP at 37 degrees C, but also led to the
      secretion of an uncleaved APP in the culture medium of CHO cells. This deletion
      did not affect A beta production from the Swedish APP but was able to inhibit the
      production of the wild-type APP. These results demonstrate that, in CHO cells,
      the internalization of the wild-type APP is needed for A beta production, while
      the production of the amyloid peptide from Swedish APP is independent of the
      internalization process.

PMID- 8573183
TI  - Study of the new stability properties induced by amino acid replacement of
      tyrosine 64 in cytochrome C553 from Desulfovibrio vulgaris Hildenborough using
      electrospray ionization mass spectrometry.
AB  - Hydrogen/deuterium exchange as well as charge state distribution monitored by
      electrospray ionization mass spectrometry were demonstrated to be a powerful and
      effective new tool for probing conformational properties of proteins in solution.
      In this paper, the influence of single amino acid replacements on the global
      conformation of cytochrome C553 from Desulfovibrio vulgaris Hildenborough using
      isotopic exchange monitored by electrospray ionization mass spectrometry is
      reported. Based on their respective charge state distributions and isotopic
      exchanges, we have differentiated relative stability of mutants and a ladder
      classification with the order being wild-type > Y64F = Y64L > Y64V > Y64A, under
      specific conditions of pH, is proposed.

PMID- 8573184
TI  - Role of the steroidogenic acute regulatory protein (StAR) in steroidogenesis.
AB  - The rate-limiting, hormone-regulated, enzymatic step in steroidogenesis is the
      conversion of cholesterol to pregnenolone by the cholesterol side-chain cleavage
      enzyme system (CSCC), which is located on the matrix side of the inner
      mitochondrial membrane. However, it has long been observed that hydrophilic
      cholesterol-like substrates capable of traversing the mitochondrial membranes are
      cleaved to pregnenolone by the CSCC in the absence of any hormone stimulation.
      Therefore, the true regulated step in the acute response of steroidogenic cells
      to hormone stimulation is the delivery of cholesterol to the inner mitochondrial
      membrane and the CSCC. It has been known for greater than three decades that
      transfer of cholesterol requires de novo protein synthesis; however, prior to
      this time the regulatory protein(s) had yet to be identified conclusively. It is
      the purpose of this commentary to briefly review a number of the candidates that
      have been proposed as the acute regulatory protein. As such, we have summarized
      the available information that describes the roles of transcription, translation,
      and phosphorylation in this regulation, and have also reviewed the supporting
      cases that have been made for several of the proteins put forth as the acute
      regulator. We close with a comprehensive description of the Steroidogenic Acute
      Regulatory protein (StAR) that we and others have identified and characterized as
      a family of proteins that are synthesized and imported into the mitochondria in
      response to hormone stimulation, and for which strong evidence exists indicating
      that it is the long sought acute regulatory protein.

PMID- 8573185
TI  - Effect of cytochrome P450 induction on the metabolism and toxicity of ochratoxin
      A.
AB  - Liver microsomes from rats treated with various P450 inducers were examined for
      their ability to metabolize the mycotoxin ochratoxin A (OTA) to 4(R)-4
      hydroxyochratoxin A (4R), the major metabolite, and 4(S)-4-hydroxyochratoxin A
      (4S), the minor metabolite. Pretreatment of rats with phenobarbital (PB),
      dexamethasone (DXM), 3-methylcolcanthrene (3MC) and isosafrole (ISF) greatly
      induced 4R formation. PB, DXM, 3MC, clofibrate (CLF) and ISF treatments also
      induced 4S formation. Isoniazid (INH) pretreatment primarily induced 4S
      formation. The pH optimum for 4R formation was found to be 6.0 with 3MC
      microsomes, and 6.5 with PB and DXM microsomes. For 4S formation, the pH optimum
      was 7.0. At the optimum pH (compared with pH 7.4), 4R formation increased 40-50%
      with PB and DXM microsomes but 8.0-fold with 3MC microsomes. Studies using the
      inhibitors metyrapone and alpha-naphthoflavone as well as monoclonal antibodies
      against various P450s suggested that at least the P450 isoforms IA1/IA2, IIB1 and
      IIIA1/IIIA2 are involved in 4R formation. Using urinary excretion of the enzymes
      alkaline phosphatase and gamma-glutamyl transferase as an index of renal damage,
      we observed that pretreatment of rats with PB, which induced hepatic P450
      (P450II2B1), protected against OTA nephrotoxicity, whereas cobalt-protoporphyrin
      IX pretreatment, which decreased P450 levels, exacerbated OTA nephrotoxicity. Our
      results suggest that at least P450IIB1-dependent metabolism of OTA leads to its
      detoxication and that OTA itself may be toxic in some circumstances or that other
      pathways are responsible for its activation.

PMID- 8573186
TI  - Activation of GTP formation and high-affinity GTP hydrolysis by mastoparan in
      various cell membranes. G-protein activation via nucleoside diphosphate kinase, a
      possible general mechanism of mastoparan action.
AB  - The wasp venom, mastoparan (MP), is a direct activator of reconstituted pertussis
      toxin-sensitive G-proteins and of purified nucleoside diphosphate kinase (NDPK)
      [E.C. 2.6.4.6.]. In HL-60 membranes, MP activates high-affinity GTPase [E.C.
      3.6.1.-] and NDPK-catalyzed GTP formation, but not photolabeling of G-protein
      alpha-subunits with GTP azidoanilide; this suggests that the venom activates G
      proteins in this system indirectly via stimulation of NDPK. Moreover, the MP
      analogue, mastoparan 7 (MP 7), is a much more effective activator of
      reconstituted G-proteins than MP, whereas with regard to NDPK and GTPase in HL-60
      membranes, the two peptides are similarly effective. In our present study, we
      investigated NDPK- and G-protein activation by MP in membranes of the human
      neuroblastoma cell line, SH-SY5Y, the human erythroleukemia cell line, HEL, the
      rat basophilic leukemia cell line, RBL 2H3, and the hamster ductus deferens
      smooth muscle cell line, DDT1MF-2. All these membranes exhibited high NDPK
      activities that were increased by MP. Compared to basal GTP formation rates,
      basal rates of high-affinity GTP hydrolysis in cell membranes were low. MP
      activated high-affinity GTP hydrolysis in cell membranes but did not enhance
      incorporation of GTP azidoanilide into G-protein alpha-subunits. As with HL-60
      membranes, MP and MP 7 were similarly effective activators of NDPK and GTPase in
      SH-SY5Y membranes. Pertussis toxin inhibited MP-stimulated GTP hydrolyses in SH
      SY5Y- and HEL membranes, whereas NDPK activations by MP were pertussis toxin
      insensitive. Our data suggest that indirect G-protein activation via NDPK is not
      restricted to HL-60 membranes but is a more general mechanism of MP action in
      cell membranes. Pertussis toxin-catalyzed ADP-ribosylation of alpha-subunits may
      inhibit the transfer of GTP from NDPK to G-proteins. NDPK may play a much more
      important role in transmembrane signal transduction than was previously
      appreciated and, moreover, the GTPase of G-protein alpha-subunits may serve as
      GDP-synthase for NDPK.

PMID- 8573187
TI  - In vitro effects of ethanol on polymorphonuclear leukocyte membrane receptor
      expression and mobility.
AB  - The hampered inflammation and host defense seen in alcoholics may be due to
      impairment of functional responses of neutrophil polymorphonuclear leukocytes
      (PMN). We have shown that ethanol inhibits the oxidative metabolism of PMN
      induced by surface receptor dependent stimuli, such as N-formyl-methionyl-leucyl
      phenylalanine (fMLP) and opsonized zymosan. Because the unresponsiveness might be
      due to reduced numbers of surface receptors, we assessed the expression of CR1,
      Fc-gamma, and fMLP receptors as well as membrane fluidity after treatment of PMN
      with ethanol in vitro. Ethanol impaired the induced expression of CR1 and fMLP
      receptors to 71% and 51% of control, respectively, but did not affect the resting
      level of CR1 nor Fc-gamma receptor expression. Furthermore, the mobility of cell
      membrane glycoconjugates was increased by ethanol. However, phagocytosis, a
      functional response dependent on membrane rheology, was unaffected. Because the
      results indicated an effect of ethanol on mobilization of receptors from
      intracellular stores, we assessed lactoferrin release, which was reduced to 59%.
      Thus, ethanol appeared to hamper the upregulation of PMN surface receptors or
      functional subsets of those stored in granules. Ethanol also increased the
      mobility of the cell membrane. These reactions were accompanied by reductions in
      the functional responses mediated by either class of receptors.

PMID- 8573188
TI  - Reduction of lipoic acid by lipoamide dehydrogenase.
AB  - Racemic lipoic acid is therapeutically applied in pathologies in which free
      radicals are involved. The in vivo reduction of lipoic acid may play an essential
      role in its antioxidant effect. It was found that mitochondrial lipoamide
      dehydrogenase (LipDH, EC 1.8.1.4.) reduces the R-enantiomer 28 times faster than
      the S-enantiomer of lipoic acid. Moreover, it was observed that the metabolites
      of lipoic acid, bisnor-, tetranor-, and beta-lipoic acid are poor substrates of
      LipDH. S-lipoic acid inhibits the reduction of the R enantiomer only at
      relatively high concentrations. The reduction of R-lipoic acid by mitochondria
      rich tissues may proceed smoothly, even if the racemic mixture is applied. This
      is of importance in elucidating the molecular mechanism of the
      pharmacotherapeutic effect of lipoic acid.

PMID- 8573189
TI  - Tyrosine hydroxylase phosphorylation in bovine adrenal chromaffin cells.
      Clonidine stimulates basal but inhibits nicotinic receptor evoked
      phosphorylation.
AB  - Clonidine inhibited the uptake of calcium and the overall phosphorylation of
      tyrosine hydroxylase induced by nicotinic receptor activation in bovine adrenal
      medullary chromaffin cells in culture. However, clonidine did not inhibit the
      increase in these parameters that accompanied K+ depolarisation of the cells.
      There was also no effect of clonidine on the overall phosphorylation of tyrosine
      hydroxylase when cells were stimulated by muscarine. Nicotinic receptor
      activation increased the phosphorylation of Ser-19, Ser-31, and Ser-40 on
      tyrosine hydroxylase, and this was inhibited by clonidine in a concentration
      dependent manner. On the other hand, clonidine had no effect on calcium uptake,
      yet increased the phosphorylation of Ser-19 under basal conditions. Using calcium
      and calmodulin-stimulated protein kinase II obtained from rat brain clonidine
      increased the autophosphorylation of the alpha-subunit of the kinase by 37%, and
      also its activity against an exogenous peptide substrate by 29%. These data are
      consistent with the hypothesis that clonidine inhibits nicotinic receptor-induced
      tyrosine hydroxylase phosphorylation by decreasing calcium influx into chromaffin
      cells, perhaps by an action at the nicotinic receptor. Clonidine also increases
      the basal phosphorylation of tyrosine hydroxylase at Ser-19, perhaps by directly
      activating calcium and calmodulin-stimulated protein kinase II.

PMID- 8573190
TI  - Liposomal incorporation changes the effect of 1.25-dihydroxyvitamin D3 on the
      phospholipase C signal transduction pathway and the eicosanoid cascade on
      keratinocytes in vitro.
AB  - 1.25-dihydroxyvitamin D3 is of clinical importance (e.g. in the treatment of
      psoriasis) given its ability to regulate the proliferation and differentiation of
      human keratinocytes. 1.25-Dihydroxyvitamin D3 mediates its action via genomic and
      nongenomic pathways. The nongenomic actions begin with the activation of
      phospholipase C and the subsequent rapid rise in calcium within the cells. We
      incorporated 1.25-dihydroxyvitamin D3 in liposomes of varying compositions in an
      attempt to improve their effect/negative side effect ratio. The influence of
      empty liposomes (1 mM) and free and liposomally incorporated 1.25
      dihydroxyvitamin D3 (10 nM) on the rapid release of sulfidoleucotrien and
      inositole 1,4,5 triphosphate was examined in keratinocytes in vitro. Free 10 nM
      1.25-dihydroxyvitamin D3 provoked a rapid rise in sulfidoleucotriens within 30
      seconds, followed by a swift decrease in sulfidoleucotrien and inositole 1,4,5
      triphosphate concentration after 10 minutes. Empty liposomes and liposomal
      incorporated 1.25-dihydroxyvitamin D3 did not show such a strong effect. These
      results suggest the occurrence of specific binding sites for 1.25
      dihydroxyvitamin D3 on the membrane level that are incapable of recognizing 1.25
      dihydroxyvitamin D3 trapped within liposomal membrane.

PMID- 8573191
TI  - Cyclosporine A decreases the protein level of the calcium-binding protein
      calbindin-D 28kDa in rat kidney.
AB  - Despite the widespread use of cyclosporine A (CsA), its mechanism of action and
      side effects are not yet completely understood. There exists a large body of
      evidence suggesting that disturbance of calcium homeostasis is a critical step in
      the cascade of cellular and molecular events induced by the drug. As recently
      shown in our laboratory by two-dimensional protein gel electrophoresis (2-DE)
      analysis of kidney homogenates, CsA induced numerous changes in several kidney
      proteins. One kidney protein in particular was shown to be strongly down
      regulated by the drug. In this work we report the identification of the strongly
      decreased kidney protein as calbindin-D 28kDa, a vitamin D-dependent calcium
      binding protein associated with calcium handling by cells. The assignment of the
      down-regulated protein spot is based on its internal amino acid sequence analysis
      and its specific reaction with a monoclonal antibody raised against calbindin-D
      28kDa. In kidney homogenates of male Wistar rats treated with 50 mg/kg/d CsA for
      up to 28 days, calbindin levels were measured by ELISA and were shown to be
      continuously decreased with prolonged CsA treatment. To our knowledge, this is
      the first report describing the effect of CsA on kidney calbindin-D 28kDa protein
      levels. Further studies are needed to elucidate whether the CsA-mediated down
      regulation of the calcium-binding protein calbindin-D 28kDa may be a critical
      factor for the renal adverse effects induced by this drug.

PMID- 8573192
TI  - The conformation of human big endothelin-1 favours endopeptidase hydrolysis of
      the TRP21-VAL22 bond.
AB  - The importance of big endothelin-1 (big ET-1) retaining a specific conformation
      for its conversion to ET-1 has yet to be determined. As a prelude to developing
      affinity labels for studying the interaction between big ET-1 and endothelin
      converting enzyme (ECE), the effect on biological activity of modifying human big
      ET-1 with the N-hydroxysuccinimide esters of 3-(p-hydroxyphenyl)propionic acid
      (HPP) or S-acetylthioglycolic acid (ATG) was investigated. Mono-derivatized HPP
      big-ET-1 and ATG-big-ET-1, and the corresponding ET-1 molecules, were purified by
      HPLC. The identity of the modified big ET-1 and ET-1 molecules were confirmed by
      mass spectrometry. Comparison of the pressor activities with big ET-1 (1 nmol/kg)
      in anaesthetized rats showed the responses to equivalent doses of HPP-big-ET-1
      and ATG-big-ET-1 to be reduced by 67% and 73%, respectively. In contrast, the
      same modifications to ET-1 had no significant effect on blood pressure responses
      or vasoconstrictor activity on the isolated rat thoracic aorta. To evaluate the
      effect of these modifications on the conversion of big ET-1 to ET-1, cultured
      bovine aortic smooth muscle (BASMC) and endothelial (BAEC) cells were used as
      sources of endothelin converting enzyme activity. After a 4-hr incubation of the
      modified molecules with intact cells, the quantity of ET-1 immunoreactivity
      generated was compared to that from unmodified big ET-1. The amount of
      conversion, relative to big ET-1 (1 microM), for HPP-big-ET-1 was reduced by 21%
      for BAEC and by 50% for BASMC. The corresponding decreases for ATG-big-ET-1 were
      79% and 82%. Because of the large decreases in the level of conversion, the
      linear big ET-1 molecule S-carboxy-amidomethylated big ET-1 (CM-big-ET-1) was
      prepared for comparison. Incubations of CM-big-ET-1 with BAEC and BASMC yielded
      only 53% and 23%, respectively, of the ET-1 immunoreactivity obtained with
      unmodified big ET-1. Thus, incorporation of the HPP or ATG groups, or removal of
      disulphide bridges decreases the ability of plasma membrane ectoenzyme ECE
      activities to hydrolyze the Trp21-Val22 bond of big ET-1. This indicates that the
      conformation of big ET-1 is important for obtaining an optimal rate of hydrolysis
      by ECE activities in vivo and in vitro. Further evidence of secondary structure
      was obtained from studies of the crossreactivity of big ET-1 in two RIAs
      recognising the ET-1 sequence.

PMID- 8573193
TI  - Exposure to the parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and
      nitric oxide simultaneously causes cyclosporin A-sensitive mitochondrial calcium
      efflux and depolarisation.
AB  - The effect of the parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+)
      together with nitric oxide donors on mitochondrial calcium homeostasis and
      membrane potential was investigated. Simultaneous exposure of calcium-loaded
      mitochondria to MPP+ and nitric oxide donors led to Cyclosporin A-sensitive
      mitochondrial calcium efflux and depolarisation. When MPP+ was replaced with the
      respiratory inhibitor rotenone, mitochondrial calcium efflux and depolarisation
      also occurred. As both MPP+ and rotenone induce mitochondrial superoxide
      formation, the possibility that calcium efflux and depolarisation were due to
      peroxynitrite formation from reaction of superoxide with nitric oxide was
      investigated. It was shown that simultaneous exposure of mitochondrial membranes
      to nitric oxide donors and rotenone led to peroxynitrite formation. The possible
      roles of nitric oxide, peroxynitrite, mitochondrial depolarisation, and calcium
      efflux in MPP+ toxicity are discussed.

PMID- 8573194
TI  - Redox cycling of beta-lapachone and related o-naphthoquinones in the presence of
      dihydrolipoamide and oxygen.
AB  - Lipophilic o-naphthoquinones (beta-lapachone, CG 8-935, CG 9-442, CG 10-248, and
      mansonones A, C, E, and F), catalyze the oxidation of dihydrolipoamide (DHLA) by
      oxygen, whereas p-naphthoquinones (alpha-lapachone and menadione) are scarcely
      active. The greatest effects corresponded to beta-lapachone and its analogues.
      Quinol production was demonstrated by (a) the absorption spectrum of the reduced
      quinone, and (b) the effect of pH variation on the rate of quinone-catalyzed DHLA
      oxidation. Superoxide dismutase (SOD) inhibited the rate of cytochrome c
      reduction and decreased the apparent rate of oxygen consumption by several DHLA/o
      naphthoquinone systems. SOD also inhibited the rate of quinol oxidation by
      oxygen, after quinone reduction by a stoichiometric amount of DHLA. Catalase
      enhanced the effect of SOD, but in its absence catalase was inactive. It is
      concluded that quinone-catalyzed oxidation of DHLA implies a free-radical
      mechanism in which the quinol and superoxide radicals play an essential role.

PMID- 8573195
TI  - Mechanistic studies on the selective inhibition of cyclooxygenase-2 by indanone
      derivatives.
AB  - The cyclooxygenase step in the conversion of arachidonic acid is a key point in
      the biosynthesis of prostanoids, managed by two enzymatic isoforms. In the
      following study we focused on the mechanism of the inhibitory action of CGP 28238
      and structurally-related indanone derivatives using purified enzymes. Consistent
      with our earlier studies on cell systems, CGP 28238 revealed selective inhibition
      of cyclooxygenase-2. The process affects the bisoxygenase subunit time
      dependently, and is reversible in the early phase of inhibition. From structure
      activity relationships, we propose the formation of a Schiff base between the oxo
      groups of CGP 28238 and an amino group at the active site providing additional
      binding forces for an effective inhibition of cyclooxygenase-2.

PMID- 8573196
TI  - Heterologous expression of the cloned guinea pig alpha 2A, alpha 2B, and alpha 2C
      adrenoceptor subtypes. Radioligand binding and functional coupling to a CAMP
      responsive reporter gene.
AB  - Functional studies have shown that 6-chloro-9-[(3-methyl-2-butenyl)oxy]-3-methyl
      1H-2,3,4,5-tetrahydro-3- benzazepine (SKF 104078) has very low affinity for
      prejunctional alpha 2-adrenoceptors (alpha 2-AR) in the guinea pig atrium. In
      this study, we have cloned guinea pig homologues of the human alpha 2-C10, alpha
      2-C4 AR subtypes and have studied them in isolation by heterologous expression in
      cultured mammalian cells. Oligonucleotide primers, designed from conserved areas
      of the human alpha 2-ARs were used in a polymerase chain reaction (PCR) with
      template cDNA synthesized from guinea pig atrial mRNA. Three PCR products were
      obtained that shared identity with the three human alpha 2-AR subtypes. A guinea
      pig (gp) genomic library was screened with a cDNA clone encoding a portion of the
      gp-alpha 2A, and genes containing the complete coding sequences of the guinea pig
      alpha 2A, alpha 2B, and alpha 2C AR subtypes were obtained. These guinea pig
      genes were subcloned into a eukaryotic expression plasmid and were expressed
      transiently in COS-7 cells. The binding of the alpha 2-selective antagonist
      [3H]MK-912 to membranes prepared from these cells was specific and of high
      affinity with Kd values of 810 pM for gp-alpha 2A, 2700 pM for gp-alpha 2B and
      110 pM for gp-alpha 2C. Competition for the binding of [3H]MK-912 by SKF 104078
      indicated that it was of moderately high affinity (approximately 100 nM) but that
      it was not selective for any of the guinea pig alpha 2-AR subtypes. Co-expression
      of guinea pig alpha 2-AR subtypes with a cyclicAMP-responsive chloramphenicol
      acetyltransferase (CAT) reporter gene resulted in agonist-dependent modulation of
      CAT activity. For the gp-alpha 2 A, a biphasic response was obtained with low
      concentrations of noradrenaline (NE) decreasing forskolin-stimulated CAT activity
      and high concentrations causing a reversal. For the gp-alpha 2B, NE produced
      mostly potentiation of forskolin-stimulated activity, and for the gp-alpha 2C, NE
      caused mainly inhibition. Overall, the pharmacology of the cloned guinea pig
      alpha 2-AR subtypes was in agreement with data obtained for the native guinea pig
      receptors and was functionally similar to that of the cloned human alpha 2-AR
      subtypes.

PMID- 8573197
TI  - Species-specific differences in taxol transport and cytotoxicity against human
      and rodent tumor cells. Evidence for an alternate transport system.
AB  - The efficacy of taxol against a wide range of sensitive and refractory solid
      tumors has prompted extensive investigation into the factors that influence its
      cytotoxicity. Our preliminary observations indicated that taxol had a superior
      antitumor effect against human cells (Daudi, K562, 2008, 2008/C13*, 2780 and C70)
      compared with its effect against rodent cells (WS, WR, NIH3T3, and CHO). Although
      verapamil, an inhibitor of P-glycoprotein function, markedly increased the
      efficacy of taxol against the rodent cells (WS, WR, and CHO), the expression of P
      glycoprotein was found only at low levels in the WR cells. In addition, levels of
      the multidrug resistance-associated protein (MRP), as assessed by reverse
      transcriptase-polymerase chain reaction analysis, were found to be higher in the
      human than in the rodent cells, although MRP mRNA was not detected by northern
      blotting. Transport studies indicated that the reduced sensitivity of the rodent
      cells to taxol was due to decreased intracellular taxol levels and reduced
      intracellular binding. However, no correlation was found between the
      intracellular binding of taxol and the intracellular levels of alpha- and beta
      tubulin, or the intracellular concentration of polymerized tubulin. These studies
      were extended further by assessing the binding of taxol to semi-purified
      microtubule proteins from WS, CHO and 2008/C13* cells in vitro. The microtubule
      protein preparations from WS, CHO and 2008/C13* cells, which have a 50-fold
      difference in their sensitivity to taxol, were found to bind equal amounts of
      radiolabeled taxol, and this binding was inhibited (80%) in the presence of
      unlabeled taxol. These results lead us to propose the presence in the rodent
      cells of an alternative taxol transport system that is distinct from the P
      glycoprotein and MRP systems.

PMID- 8573198
TI  - 7-Ethoxycoumarin O-deethylation catalyzed by cytochromes P450 1A2 and 2E1 in
      human liver microsomes.
AB  - 7-Ethoxycoumarin O-deethylation has been used widely as a marker activity for
      assessing substrate specificities of cytochromes P450 (P450) in liver microsomes
      of mammals, and extensive studies have shown that in rats and mice the major
      catalysts are P450 1A1, 1A2, and 2B enzymes. In contrast to findings in
      experimental animal models, P450 2E1 has been reported to be a principal enzyme
      involved in 7-ethoxy-coumarin O-deethylation in human livers. In this study, we
      further examined the roles of individual forms of human P450 involved in 7
      ethoxycoumarin O-deethylation using microsomes from different human liver samples
      and from human lymphoblastoid cells expressing human P450 enzymes and purified
      P450 enzymes isolated from the membrane of Escherichia coli expressing modified
      P450 proteins. Kinetic analysis showed that there were at least two different
      enzymes involved in 7-ethoxycoumarin O-deethylation in different human samples.
      Samples that contained high amounts of P450 2E1 in liver microsomes showed
      biphasic curves for O-deethylation with relatively high turnover numbers, whereas
      P450 1A2-rich samples tended to have low Km values with low Vmax values. Anti
      human P450 2E1 antibodies inhibited markedly (P < 0.05) the 7-ethoxycoumarin O
      deethylation activities catalyzed by human liver microsomes particularly when
      examined at a high substrate concentration (200 microM). However, we also found
      that anti-P450 1A2 antibodies suppressed O-deethylation activities only at a low
      substrate concentration (10 microM). Recombinant human P450 1A2 was found to have
      a low Km value for 7-ethoxycoumarin O-deethylation, whereas P450 2E1 showed a
      high Km value. Of the P450 enzymes examined, P450 1A1 gave the highest O
      deethylation activities with a low Km value, although this enzyme is reported to
      be expressed extrahepatically in humans. Other human P450 enzymes, including P450
      2A6, 2C10, 2D6, 3A4, and 3A5, did not show significant O-deethylation activities
      except that P450 2B6, a minor P450 component in human livers, was found to have a
      Vmax value similar to that of P450 1A2 and a Km value similar to that of P450
      2E1. These results suggest that P450 1A2 is a low Km enzyme for 7-ethoxycoumarin
      O-deethylation in human liver microsome, although it has a low Vmax value than
      P450 2E1.

PMID- 8573199
TI  - Effects of taurine and guanidinoethane sulfonate on toxicity of the pyrrolizidine
      alkaloid monocrotaline.
AB  - Monocrotaline (MONO), a pyrrolizidine alkaloid, causes pulmonary arterial
      hypertension and right ventricular hypertrophy due to hepatic metabolism to the
      alkylating pyrrole dehydromonocrotaline. Taurine a sulfonic amino acid, is hepato
      and cardioprotective in a variety of conditions. We have examined the effects of
      taurine and its amidino analog, guanidinoethane sulfonate (GES), in rats injected
      i.p. with MONO (65 mg/kg). Taurine and GES were given as 1% solutions in drinking
      water beginning 14 days before administration of MONO and continuing for 14 days
      therafter, when the rats were killed. The MONO group had right ventricular
      hypertrophy and pulmonary hyperplasia. Compared with control, no significant
      changes in the right ventricle/left ventricle weight ratio, or the right
      ventricle/body weight ratio occurred in rats also given taurine of GES. Lung
      weights in these two groups were higher than in the control group, but below that
      of the MONO-alone group. The lethality of MONO over 14 days was decreased by
      taurine (LD50 for MONO alone 80 mg/kg; for MONO + taurine 121 mg/kg). Rats given
      only MONO had lower hepatic concentrations of GSH and cysteine (Cys), and higher
      activities of microsomal GSH transferase activity were no different from control.
      Gamma-Glutamylcysteine (Glu-Cys) synthetase and gamma-glutamyl transpeptidase
      activities were elevated. In MONO-injected rats given GES, hepatic GSH levels
      were higher and Cys levels were lower than in either the MONO alone or MONO +
      taurine groups. Gamma-Glu-Cys synthetase activity was depressed. Microsomal GSH
      transferase, GSH peroxidase and gamma-glutamyl transpeptidase activities were
      elevated. Livers of MONO-injected animals showed higher levels of serine
      (reversed by both taurine and GES) and glycine (Gly; reversed by GES) and lower
      levels of glutamine. Compared with control rats, the following changes occurred
      in serum amino acids: MONO alone: increased aspartate, taurine and lysine;
      taurine-supplemented: increased taurine, methionine (Met) and lysine, and
      decreased Gly; GES-supplemented: decreased asparagine, serine, Gly, arginine,
      taurine, and valine. Compared with the MONO-alone group, the taurine-supplemented
      group had higher glutamate (Glu), Met and alanine, and the GES-supplemented group
      higher alanine and lower serine, Gly, arginine and valine. We conclude that
      taurine protects against MONO-induced lethality and right ventricular
      hypertrophy. GES also protects against right ventricular hypertrophy. However,
      these agents act by different mechanisms, taurine preventing many of the
      biochemical changes induced by MONO, with GES inducing additional changes.

PMID- 8573200
TI  - Chlorpromazine stimulatory effect on iron uptake by rat brain synaptosomes.
AB  - Clinical long-term neuroleptic administration induces extrapyramidal motor side
      effects, of which tardive dyskinesia is the most important. Experimentally,
      dopamine D2 supersensitivity is observed after phenothiazine and butyrophenone
      treatment. Neuroleptic-induced tardive dyskinesia and D2 modulation have been
      linked to impaired iron homeostasis in the central nervous system. Increased
      nonheme iron levels found in the basal ganglia of patients with extrapyramidal
      symptomology support the connection between iron and neuronal dopaminergic
      modulation. We now report the effect of chlorpromazine on iron uptake by
      synaptosomes of rat brain from two different iron donors: [55Fe]citrate and
      [55Fe]transferrin. Iron uptake from both donors by cortical synaptosomes was
      stimulated by Ca2+ and enhanced by chlorpromazine in a saturable fashion.
      Synaptosomes from the striatum also showed increased (60%) iron uptake from
      [55Fe]citrate in the presence of chlorpromazine. Chlorpromazine stimulated iron
      uptake by cortical synaptosomes more efficiently than Ca2+, at physiological
      levels, from both [55Fe]transferrin (50%) and [55Fe]citrate (68%). Calcium
      potentiated the effect of chloropromazine upon cortical synaptosomal iron uptake
      from [55Fe]citrate, but had no apparent effect on the uptake from
      [55Fe]transferrin. Chlorpromazine-stimulated iron uptake from the latter was
      observed without addition of Ca2+. Moreover, fluorescence measurement of Ca2+
      uptake by cortical synaptosomes showed intensified uptake in the presence of 50
      microM chlorpromazine (42%). Visible spectral studies of chlorpromazine in the
      presence of Fe(3+)-citrate and diferric-transferrin did not reveal iron
      displacement by chlorpromazine from either of the two donors. These data suggest
      that chlorpromazine may increase iron uptake by neurons, and may be involved in
      the development of tardive dyskinesia and other extrapyramidal disorders.

PMID- 8573201
TI  - Specific inhibition of Na+,K(+)-ATPase activity by atractylon, a major component
      of byaku-jutsu, by interaction with enzyme in the E2 state.
AB  - Atractylon, a major component of the crude drug "Byaku-jutsu" (rhizomes of
      Atractylodes japonica), strongly inhibited Na+,K(+)-ATPase activity with an I50
      value of 8.9 x 10(-6) M. It also inhibited Mg(2+)-ATPase, H+,K(+)-ATPase, H(+)
      ATPase and Ca(2+)-ATPase activities, but less potently. No effects on alkaline
      and acid phosphatase activities were observed. The inhibition of Na+,K(+)-ATPase
      activity by atractylon was noncompetitive with respect to ATP and was greater
      with increasing K+ concentration, whereas it was not affected by Na+
      concentration. The activity of K(+)-dependent p-nitrophenyl phosphatase, a
      partial reaction of Na+,K(+)-ATPase, was inhibited noncompetitively with respect
      to substrate (I50 value of 1.8 x 10(-5) M), and the inhibition rate was
      independent of the K+ concentration. Furthermore, atractylon increased the Ki
      value for Na+ from 130 to 190 mM, but did not alter the Ki value for ATP.
      Inhibition of the phosphoenzyme formation by atractylon was greater at 0.1 M than
      at 1 M NaCl. K(+)-dependent dephosphorylation (E2-P to K.E2) was inhibited by
      atractylon, whereas ADP-sensitive (Na.E1-P to Na.E1) and non-specific
      dephosphorylation steps were not affected. These results suggest that atractylon,
      a specific inhibitor of Na+,K(+)-ATPase, interacts with enzyme in the E2 state
      and inhibits the reaction step from E2-P to K.E2.

PMID- 8573202
TI  - Transcriptional regulation of the CYP2B1 and CYP2B2 genes by C/EBP-related
      proteins.
AB  - Cytochrome P450 (CYP) 2B1 and 2B2 are encoded by two closely related genes,
      CYP2B1 and CYP2B2, that are expressed at low levels in adult rat liver but are
      induced markedly by the administration of the drug phenobarbital (PB) or other
      structurally unrelated hydrophobic compounds to animals. Very little is
      understood about the molecular mechanisms that control both basal and induced
      transcription of these genes. We have identified two liver specific DNase I
      hypersensitive sites associated with the CYP2B1 and CYP2B2 (CYP2B) genes. One
      site, which maps to a region in the 5'-flanking region between -2.2 and -2.3 kb,
      became more resistant to DNase I cleavage in nuclei from PB-treated rats; the
      converse was true of the other hypersensitive site, which maps to the proximal
      promoter region between -0.05 and -0.15 kb. DNase I footprint analysis revealed
      three prominent and one weak footprinted regions in the promoter region in the
      vicinity of the proximal hypersensitive site. Using competitor oligonucleotides,
      we determined that one footprinted region (FT2), between -42 and -66 bp, is
      likely to represent a binding site for CCAATT enhancer binding protein (C/EBP)
      family members. Indeed, bacterial expressed recombinant C/EBP alpha bound at this
      site and formed a footprint pattern identical to the pattern observed with liver
      nuclear extract. In vitro transcription assays demonstrated that the FT2 site
      contributed strongly to promoter activity, since its mutation reduced
      transcription by 80%. Two other sites identified by footprint analysis (FT1 and
      FT3) are also required to maintain high basal transcription of CYP2B2 promoter
      constructs in an in vitro transcription assay. Transient transfection experiments
      confirmed the expectation that C/EBP alpha could activate the 1.4 kb CYP2B
      promoter constructs, with mutation of the FT2 site impairing both basal
      transcription and transactivation by exogenous C/EBP alpha.

PMID- 8573203
TI  - Impact of tamoxifen on peripubertal androgen imprinting of rat hepatic cytochrome
      P450 2C11, cytochrome P450 3A2, and steroid 5 alpha-reductase.
AB  - Expression of sex-dependent rat hepatic cytochromes P450 and steroid 5 alpha
      reductase is regulated mainly by the sex-specific pattern of growth hormone (GH)
      secretion and is subject to androgen imprinting. Since tamoxifen suppresses GH
      pulse amplitude and nadir levels, we investigated the effect of tamoxifen on
      peripubertal testosterone imprinting of hepatic CYP2C11, CYP3A2, CYP2A1, and
      steroid 5 alpha-reductase. Prepubertal tamoxifen administration (5 mg once daily
      s.c. on days 28 and 29 of age) to non-ovariectomized female Sprague-Dawley rats
      did not affect hepatic microsomal CYP2C11-dependent testosterone 2 alpha
      hydroxylase, CYP3A-mediated testosterone 6 beta-hydroxylase, CYP2A1-dependent
      testosterone 7 alpha-hydroxylase, or steroid 5 alpha-reductase activity in adult
      rats. Testosterone treatment (5 mumol/kg, s.c., once daily) of intact female rats
      during either puberty (days 35-49 of age) or adult life (days 69-77 of age) had
      no effect on these enzyme activities in adult (78-day-old) female rats, but the
      same treatment given during both of these periods induced the male-specific
      testosterone 2 alpha- and 6 beta-hydroxylase activities and suppressed the female
      predominant testosterone 7 alpha-hydroxylase and steroid 5 alpha-reductase
      activities, indicating that peripubertal testosterone administration imprints the
      adult androgen responsiveness but not the basal levels of these enzyme activities
      in non-ovariectomized female rats. However, peripubertal androgen imprinting of
      the basal levels of testosterone 2 alpha-hydroxylase and steroid 5 alpha
      reductase activities was observed in female rats administered tamoxifen
      prepubertally. Tamoxifen pretreatment also enhanced testosterone imprinting of
      the adult androgen responsiveness of testosterone 2 alpha- and 6 beta-hydroxylase
      and steroid 5 alpha-reductase activities. The enhanced testosterone hydroxylase
      activities were, however, not associated with an increase in microsomal NADPH
      cytochrome P450 reductase activity, but were accompanied by elevated hepatic
      CYP2C11 and CYP3A2 protein levels. Overall, the present study indicates that
      prepubertal tamoxifen administration does not interfere with the normal sex
      differentiation of the gender-dependent hepatic cytochromes P450 and steroid 5
      alpha-reductase, but this drug modulates peripubertal androgen imprinting of
      CYP2C11, CYP3A2, and steroid 5 alpha-reductase in adult female rats.

PMID- 8573204
TI  - Heterogeneous expression of sulphotransferases in periportal and perivenous
      hepatocytes prepared from male and female rat liver.
AB  - Sulphotransferase (ST) is a family of enzymes responsible for metabolism and
      detoxication of endobiotics and xenobiotics. We investigated the hepatic acinar
      distribution of three sulphotransferases: phenol sulphotransferase (PST),
      oestrogen sulphotransferase (EST), and hydroxysteroid sulphotransferase (HST) in
      male and female rat livers by measurement of enzyme activities in isolated
      periportal and perivenous hepatocytes. The distribution was confirmed by
      immunohistochemistry. EST activity was located predominantly in the perivenous
      hepatocytes in male rats but not in female rats, where residual activity is
      catalysed by another ST. HST activity was not significantly different in
      periportal and perivenous hepatocytes in either male or female rats. For PST, a
      more widespread distribution was observed, with slight predominance in the
      periportal regions. The results indicate heterogeneous distribution of ST
      isoenzymes in the periportal and perivenous hepatocytes isolated from male and
      female rat livers.

PMID- 8573205
TI  - Effects of monocrotaline, a pyrrolizidine alkaloid, on glutathione metabolism in
      the rat.
AB  - Monocrotaline (MONO), a pyrrolizidine alkaloid, causes veno-occlusive disease of
      the liver, pulmonary arterial hypertension, and right ventricular hypertrophy.
      Toxicity is due to the hepatic formation of a pyrolic metabolite that can be
      detoxified by conjugation with glutathione (GSH). We have shown that the GSH
      content of the liver affects the quantity of the pyrrolic metabolite that is
      released from the liver. We have now examined whether MONO, in turn, affects GSH
      metabolism. Twenty-four hours after administration of MONO to rats (65 mg/kg,
      i.p.), the highest concentration of bound pyrrolic metabolites was found in the
      liver, followed by the lung and kidney. Heart and brain contained lower
      concentrations of these metabolites. Significantly higher levels of GSH were
      found in liver and lungs of MONO-treated rats than in saline-injected control
      animals. In the liver, activities of the following enzymes were elevated: gamma
      glutamylcysteine synthetase, GSH synthetase, gamma-glutamyl transpeptidase,
      dipeptidase, and microsomal GSH transferase. The same changes were seen in the
      lung. In the heart, gamma-glutamyl transpeptidase activity was decreased
      markedly, and cytosolic GSH transferase activity was elevated. In the kidney, the
      activities of GSH synthetase, gamma-glutamyl transpeptidase, and cytosolic GSH
      transferase were increased. Our results establish a mutual interaction of MONO
      and sulfur metabolism. It appears that an early metabolic action of MONO is to
      modify sulfur amino acid metabolism, diverting cysteine metabolism from oxidation
      to taurine towards synthesis of GSH.

PMID- 8573206
TI  - [C-reactive protein: structure, properties, and methods of isolation].
AB  - Data on the structure, properties, and biosynthesis of C-reactive protein (CRP)
      are summarized. Special attention is paid to the specific interaction of C
      reactive protein with Ca(2+)-dependent and Ca(2+)-independent ligands:
      phosphorylcholine-containing compounds, lipoproteins, chromatin, galactans,
      polycations, etc. The data on the interaction of CRP with Ca2+ are presented. The
      methods for the CRP isolation and purification are discussed with an emphasis on
      affinity chromatography as the most promising method for obtaining purified CRP.

PMID- 8573207
TI  - [Identification of immunoreactive epitopes in proteins coded by gag, env, and pol
      genes of the type I human T-lymphotropic virus (HTLV-I) using synthetic
      peptides].
AB  - Reactivity of 26 synthetic peptides that comprise 12 to 26 amino acid residues
      corresponding to segments of the gag p19, env gp46, and pol proteins of human T
      lymphotropic virus type I toward 31 positive sera was studied using enzyme-linked
      immunosorbent assay. Specific reactivity with high titers of antibodies
      (presented in reciprocal dilution values) was detected for the synthetic peptides
      corresponding to fragments 110-130 and 100-130 (titers up to 4050) of p19, 174
      197 (up to 800), 186-201 (up to 4050), 191-215 (up to 1350), 242-257 (up to 800),
      and 272-292 (up to 450) of gp46. Immunoreactivity of seven peptides, fragments of
      pol-proteins, was weak. New linear epitopes in the regions 145-158, 272-277, and
      292-300 of gp46 were detected. In addition, location of the known linear epitopes
      in p19 and gp46 was refined on the basis of comparative study of overlapping
      peptides from these proteins.

PMID- 8573208
TI  - [ECP 32 proteinase: characteristics of the enzyme, study of specificity].
AB  - Hydrolysis of the C-peptide from recombinant human proinsulin, porcine insulin,
      and melittin by the E. coli actin-degrading proteinase ECP 32 was studied by
      reverse phase high performance liquid chromatography and mass spectrometry with
      electrospray ion source. Proteinase ECP 32 hydrolyzed only melittin at the Ala15
      Leu16 or Leu16-Ile17 bonds (KM = 2.4 x 10(-6) M). The effects of pH and buffer
      composition on the rate of enzymatic hydrolysis were studied. The pH optimum of
      melittin hydrolysis was 7. Phosphates inhibited, whereas ATP stimulated the
      hydrolysis of melittin. Melittin was suggested as a substrate for determining the
      activity of proteinase ECP 32.

PMID- 8573209
TI  - [Kinetics of DNA photomodification by derivatives of 1-(3-(p
      azidotetrafluorobenzoyl)aminopropyl)-5'-phosphamides of oligodeoxyribonucleotides
      in model duplexes].
AB  - Kinetics of photomodification of 26-meric deoxyribonucleotide pTTGCCTTGAATGGGAA
      GAGGGTCATT with derivatives of the complementary oligonucleotides pTCTTCCCATTC,
      pTCTTCCCA, and pTTCCCA bearing a residue of (p
      azidotetrafluorobenzoyl)aminopropylamine(-ArN3) attached to the terminal
      phosphate (reagents I, II, and III, respectively) was studied at 37 degrees C. It
      was established that during irradiation the reagents are inactivated, loosing
      their affinity to the target. A kinetic equation describing the modification was
      suggested. From the dependence of the time-limited modification level on the
      reagent concentration, the association constants of the reagents with the target
      were determined: [Kx = (9.9 +/- 0.4) x 10(4), (1.1 +/- 0.1) x 10(5), and (8.4 +/-
      2.1) x 10(6) M-1 for reagents I, II, and III, respectively] and the efficiency of
      the modification in the complex gamma ef (ca. 0.3 for all the reagents) were
      determined. From the dependence of the modification level [PZ]/p0 on time for
      reagent II, the rate constant was determined for the rate-determining step of the
      photomodification k0 = (7.9 +/- 0.9) x 10(-3) s-1, which is close to the rate
      constant for the photolysis of p-azidotetrafluorobenzoic acid kp = (5.5 +/- 0.3)
      x 10(-3) s-1.

PMID- 8573210
TI  - [Synthesis of modified oligonucleotides and use of a duplex from them with
      covalently bound chains].
AB  - A method for the synthesis of DNA duplex with covalently linked strands was
      elaborated, and the thermal and hydrolytic stability of the duplex was studied.
      The strands were connected via an amide bond between carboxyl and aliphatic amino
      groups in the presence of water-soluble carbodiimide. For this purpose, a series
      of modified 5- to 26-mer oligonucleotides with primary amino or carboxyl group
      were prepared, and their properties were investigated.

PMID- 8573211
TI  - [Substrate properties of dioxolane analogs of 3'-deoxythymidine-5'-triphosphate
      in DNA synthesis reactions, catalyzed by various DNA polymerases].
AB  - The substrate properties of 3'-deoxythymidine 5'-triphosphate analogs prepared on
      the basis of 2,4-disubstituted 1,3-dioxolanes were investigated in reactions of
      the DNA synthesis catalyzed by various DNA polymerases. The 4'-triphosphates of
      (+/-)-cis-4-hydroxymethyl-2-(1-thyminylmethyl)-1,3-dioxolane and the
      corresponding (+/-)-trans-isomer were shown to be terminating substrates of
      terminal deoxynucleotidyl transferase. 4'-Triphosphate of (+/-)-cis-4
      hydroxymethyl-2-(1-thyminylmethyl)- 1,3-dioxolane terminates the DNA synthesis
      catalyzed by HIV reverse transcriptase, whereas 2'-triphosphate of (+/-)-cis-2
      hydromethyl-4-(1-thyminylmethyl)-1,3-dioxolane is a terminator in the DNA
      synthesis catalyzed by HIV reverse transcriptase and the Klenow fragment of DNA
      polymerase I.

PMID- 8573212
TI  - [Compounds similar to acyclovir. IX. Synthesis of 7-hydroxy-2,5-dioxaheptyl
      nucleic acid derivatives].

PMID- 8573213
TI  - [Evolutionary programming for finding "structure-activity" relationships in a
      series of 3-phenoxychromone and 3-phenoxy-4-hydroxycoumarin derivatives].
AB  - Based on a set of compounds possessing hypolipidemic activity, it was
      demonstrated that evolutionary algorithms can be successfully used to compile an
      informative set of molecular parameters. The parameter sets selected using the
      method of potential functions allowed correct prediction of the activity of test
      molecules.

PMID- 8573214
TI  - Analysis of anticonvulsant and neurotoxic responses to combination therapy with
      carbamazepine, felbamate and phenytoin by response-surface modeling.
AB  - Various combinations of carbamazepine (CAS 298-46-4), felbamate (CAS 25451-15-4),
      and phenytoin (CAS 57-41-0) were evaluated in mice (i.p.) for anticonvulsant
      activity (maximal electroshock seizure test) and minimal neurotoxicity (rotarod
      test). The results obtained from these studies were analyzed using response
      surface methodologies (RSM). The outcomes of these analyses in regard to
      anticonvulsant activity suggest that, under these experimental study conditions,
      at 0.5 h post treatment there is a significant carbamazepine/phenytoin synergism
      even though none of the drugs has a significant dose-response by that time when
      given alone, and that at 1.0 h post treatment, the combination dose-response is
      additive. Thus, there appears to be an important dose/time relationship. In
      regard to the neurotoxic response, the results suggest a significant
      carbamazepine/phenytoin synergism at 0.25 h post treatment and an additive
      neurotoxic effect due to the combination of felbamate/carbamazepine/phenytoin at
      0.5, 1.0 and 2.0 h post exposure.

PMID- 8573215
TI  - In vitro metabolism of nefiracetam by liver microsomes from rats, dogs and
      monkeys.
AB  - The in vitro metabolism of nefiracetam (CAS 77191-36-7, N-(2,6-dimethylphenyl)-2
      (2-oxo-1-pyrrolidinyl) acetamide, NEF, DM-9384), a novel cognition enhancer, has
      been investigated using liver microsomes from rats, dogs and monkeys. Microsomal
      metabolism of NEF showed qualitatively a similar profile in three species tested.
      Six metabolites were generated from incubation of NEF with liver microsomes.
      Their structures were identified using a thermospray LC/MS/MS (liquid
      chromatography/tandem mass spectrometry) method, as regioisomers of
      monhydroxylated derivatives of NEF: the 3-hydroxy (3-OH-NEF); 4-hydroxy (4-OH
      NEF); 5-hydroxy (5-OH-NEF); 3'-hydroxy (3'-OH-NEF); 4'-hydroxy (4'-OH-NEF);
      hydroxymethyl (HM-NEF) metabolites. The heat lability, NADPH requirement and
      inhibition by prototype cytochrome P450 inhibitors (proadifen and metyrapone)
      implies that NEF oxidations are catalyzed by cytochromes P450. The major
      metabolic route was 5-OH-NEF formation in all species, corresponding well with
      the previous investigations in vivo. Inhibitory effects of alpha-naphthoflavone
      and quinidine on NEF hydroxylation suggest that several isoforms of cytochromes
      P450 are involved in the formation of these NEF metabolites.

PMID- 8573216
TI  - In vitro study on the interaction of Valeriana officinalis L. extracts and their
      amino acids on GABAA receptor in rat brain.
AB  - This work studied in vitro the interaction of aqueous and hydroalcoholic extracts
      of Valeriana officinalis L. and compounds that are present in the extracts (amino
      acids and valerenic acid) with the GABAA (gamma-aminobutyric acid) receptor,
      using the [3H] muscimol binding technique to crude synaptic membranes from rat
      brain cortices. Both extracts displaced [3H]muscimol bound and this effect is
      probably due only to their amino acid content, specially GABA. This fact explains
      the in vitro effect of valerian extracts on GABAA receptor but not their sedative
      effect.

PMID- 8573217
TI  - Stereoselective anticonvulsant activity of the enantiomers of (+/-)-2-hydroxy-2
      phenylbutyramide.
AB  - The enantiomers of the anticonvulsant DL-2-hydroxy-2-phenylbutyramide (1) were
      prepared by resolving the (-)-quinine and (+)-1-phenylethylamine salts of the
      acids. The optically active acids were then esterified and reacted with ammonia
      to give (+)-1 and (-)-1. Optical purity of the amides was greater than 99.9%
      enantiomeric excess by chiral HPLC. Examination of the infrared spectra of the
      enantiomers and the racemate of 1 in chloroform solution showed identical
      spectra, but the spectrum of the racemate in a KBr disc was somewhat different
      from those of the pure enantiomers. Pharmacologically, 1 and its enantiomers have
      a similar significant anticonvulsant activity at peak drug effect against
      pentylenetetrazol seizures, but a variation in time between the enantiomers was
      found with the anticonvulsant activity. In the rotarod ataxia test (-)-1
      possessed the lowest neurotoxicity.

PMID- 8573218
TI  - Acute, subacute and chronic oral toxicity studies of the new serotonin (5-HT)3
      receptor antagonist ramosetron in beagle dogs.
AB  - The oral toxicity of ramosetron ((R)-5-[(1-methyl-3-indolyl) carbonyl]-4,5,6,7
      tetrahydro-1H-benzimidazole hydrochloride, CAS 132907-72-3, YM060), a new
      compound having serotonin (5-HT)3 receptor antagonist activity was investigated
      in beagle dogs. To evaluate the acute toxicity, two groups of beagle dogs, each
      comprised of one male and one female, were given YM060 bulk powder in gelatin
      capsules at dose of 0, 3 mg/kg or 0, 30 and 60 mg/kg in ascending order in at
      least 7-day intervals. After the final dose, animals were observed for 2 weeks.
      No deaths were observed at any dose. At 60 mg/kg, the male exhibited frequent
      vomiting, salivation and prone position 1-3 h after administration, when the
      plasma concentration of the unchanged drug reached Cmax or was close to Cmax. The
      female exhibited no changes except vomiting. No effects on either the male or the
      female were detected in body weight, food consumption, electrocardiography,
      hematology, plasma biochemistry or urinalysis. To evaluate the subacute toxicity
      of YM060, three male and 3 female beagle dogs per group received doses of 0, 1,
      3, 10 and 20 mg/kg/d for 13 weeks. YM060 was triturated 10-fold using lactose and
      filled in gelatin capsules before use. The plasma concentration of unchanged drug
      increased almost dose-dependently, peaked about 2 h post-dosing and subsequently
      decreased with time. The plasma concentration-time profile after the final dose
      at week 13 was not different from that after the initial dose. No treatment
      related changes were observed up to 3 mg/kg/d.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8573219
TI  - Identification of efonidipine hydrochloride metabolites in rats.
AB  - The metabolism of efonidipine hydrochloride (CAS 111011-76-8, NZ-105), a new
      dihydropyridine calcium antagonist, was studied after oral or intraperitoneal
      dosing in rats. Six metabolites were isolated from urine and bile and their
      structures were confirmed by spectral and chromatographic comparison with the
      authentic compounds. The main metabolic pathway of efonidipine hydrochloride
      involved N-debenzylation, N-dephenylation, oxidative deamination, ester
      hydrolysis and oxidation of the 1,4-dihydropyridine ring to the corresponding
      pyridine.

PMID- 8573220
TI  - Characterization of the phosphodiesterase inhibition by 2-(3-methoxy-5
      methylsulfinyl-2-thienyl)-1H-imidazo-(4,5-c)-pyridine HCl and its sulfide- and
      sulfone derivatives in myocardial preparations from failing human hearts.
AB  - The effects of HN-10200 (2-(3-methoxy-5-methylsulfinyl-2-thienyl)-1H-imidazo(4,5
      c)-pyridine HCl) and its derivatives HN-10201-sulfide and HN-10202-sulfone on the
      activities of the phosphodiesterase (PDE) isoenzyme activities isolated from
      ventricular myocardium of failing human hearts (end-stage myocardial failure,
      NYHA IV) were investigated. Four PDE isoenzymes (PDE I-IV) were separated by DEAE
      sepharose chromatography. Milrinone, 3-isobutyl-1-methylxanthine (IBMX), and a
      derivative of pimobendan (2-(4-hydroxyphenyl)-5-(5-methyl-3-oxo-4,5-dihydro-2H-6
      pyridazinyl)- benzimidazole HCl, PiD) were studied for comparison. Furthermore,
      the influence of HN-10200 on force of contraction and cAMP content of ventricular
      trabeculae of these hearts were determined. HN-10200 inhibited the activities of
      PDE I-IV concentration-dependently. The IC50 values were (mumol/l): 218.7, 283.1,
      119.6, and 85.8 for PDE I-IV, respectively. The IC50 values of its derivatives
      were in the same range, i.e. the parent compound or its derivatives inhibited the
      PDE isoenzymes nonselectively. IBMX also inhibited PDE I-IV nonselectively, but
      was about ten times more potent based on IC50 values. In contrast, PiD was the
      most selective and potent PDE III inhibitor tested. Milrinone inhibited both, PDE
      III and IV, up to two orders of magnitude more potently than PDE I and II, HN
      10200 (30 mumol/l) only marginally and insignificantly increased force of
      contraction and cAMP content of the ventricular trabeculae. Thus, HN-10200 and
      it's derivatives HN-10201-sulfide and HN-10202-sulfone are nonselective
      inhibitors of myocardial PDE I-IV. HN-10200 revealed only neglectable positive
      inotropic effects in preparations from failing human heart.

PMID- 8573221
TI  - Inhibition of nisoldipine on bovine mesenteric arteries and veins and on human
      peripheral veins.
AB  - The inhibiting effect of the calcium channel blocker nisoldipine (CAS 63675-72-9,
      Baymycard, Syscor) on potassium-induced contraction on bovine mesenteric veins
      and arteries and human peripheral veins was investigated. Nisoldipine inhibited
      the contraction on bovine mesenteric veins at a significantly lower concentration
      (1 x 10(-10) mol/l) than nifedipine and glyceryl trinitrate (GTN) (1 x 10(-7)
      mol/l). When the preparations were preincubated with the drugs, nisoldipine
      reduced the contraction, measured as area under the curve (AUC), with 47 +/- 8%
      (mean +/- SEM) and nifedipine with 29 +/- 13% in veins. It was necessary to use
      an inconsiderably higher concentration of nisoldipine to relax bovine mesenteric
      arteries contracted by potassium. Preincubation of these arteries with
      nisoldipine (1 x 10(-7) mol/l) reduced contraction measured as AUC by 46 +/- 10%
      and preincubation with nifedipine (1 x 10(-7) mol/l) by 77 +/- 3%. Nisoldipine
      also caused a marked relaxation in human saphenous veins. The introduction of
      nisoldipine (1 x 10(-8) mol/l) after potassium-induced contraction caused 54 +/-
      8% relaxation.

PMID- 8573222
TI  - Pharmacokinetics and bioavailability of pentaerithrityl tetranitrate and two of
      its metabolites.
AB  - Two preparations containing 100 mg pentaerithyrityl tetranitrate (PETN, CAS 78-11
      5) each were administered to 24 healthy male volunteers in an open randomised two
      way cross-over design. The test preparation was a commercially available 50 mg
      tablet (Pentalong 50 mg Tabletten, 2 tablets per dose), the reference preparation
      was an aqueous suspension prepared immediately before application from the same
      25% PETN/lactose trituration as was used for manufacturing the tablets. Blood
      samples were withdrawn pre-dose and at 14 time points within 24 h after dosing.
      The resulting plasma was analysed by a GC/MS method developed on purpose. Since
      in a pilot study not a single one of 120 plasma samples contained concentrations
      of unchanged PETN or of its metabolite pentaerithrityl trinitrate (PE-tri-N, CAS
      1607-17-6) above the quantification limit of 50 pg/ml, the samples of this study
      were assayed for the metabolites pentaerithrityl dinitrate (PE-di-N, CAS 1607-01
      8) and pentaerithrityl mononitrate (PE-mono-N, CAS 1607-00-7) only. -Mean peak
      levels of 17 ng/ml and 7.5 ng/ml PE-di-N were reached ca. 3 h after application
      of tablets or trituration. The plasma elimination half-life was 4-5 h. Average
      maximum PE-mono-N levels of 79 ng/ml (tablets) and 35 ng/ml (trituration) were
      observed at 7 h p. appl. They declined with a half-life of 10-11 h. The relative
      bioavailability of the tablets as determined by means of the AUC of PE-di-N is
      280-290%. This high value is explained by the specific properties of drug
      liberation and dissolution from the preparations used.

PMID- 8573223
TI  - Pharmacokinetics and pharmacodynamics of nisoldipine in hypertensive patients
      with normal and mild to moderate impaired renal function.
AB  - The pharmacokinetics and pharmacodynamics of nisoldipine (CAS 63675-72-9,
      isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5
      pyridinedicarboxylate, Bay k 5552), a calcium antagonist, were investigated after
      administration of a single oral 10 mg dose and after 7 same doses on consecutive
      days to hypertensive patients with normal renal function (NRF) and those with
      mild to moderate renal dysfunction (impaired renal function, IRF). A significant
      decrease in blood pressure was observed after consecutive dosing of nisoldipine
      compared to baseline values over 24 h in both groups. There were no significant
      differences in plasma profiles of nisoldipine in both groups after either single
      or consecutive dosing. The plasma concentration-time profiles of the active
      metabolite, Bay r 9425, were similar to those of nisoldipine in both groups. The
      pharmacokinetic parameters of nisoldipine and its active metabolite in the NRF
      and IRF groups did not differ after the single and the consecutive dosing. In
      addition, there were neither prolongation of apparent elimination half-life
      (t1/2), nor increases in peak plasma levels (Cmax), or the area under the plasma
      concentration-time curve (AUC0-infinity) after consecutive dosing in both groups.
      Cumulative urinary excretion rates of the major metabolites, Bay s 4755 and Bay s
      1869, did not differ significantly between the NRF and IRF groups in both single
      and consecutive studies. In the present study, mild flushing was observed in one
      patient with IRF. There was no deterioration in renal function during the study.
      These results suggest that nisoldipine may have a long-lasting antihypertensive
      effect during consecutive dosing and that it can be used in hypertensive patients
      regardless of presence of renal dysfunction.

PMID- 8573224
TI  - Different hemodynamic effects of celipropol and atenolol in patients with mild to
      moderate hypertension.
AB  - The hemodynamic effects of celiprolol (CAS 56980-93-9), a betablocker with beta 1
      antagonist and beta 2 agonist properties, were compared with those of atenolol
      (CAS 29122-68-7) in 12 patients with mild to moderately severe hypertension
      (diastolic BP 95-110 mmHg). Celiprolol and atenolol lead to a similar and
      significant reduction of systolic and diastolic blood pressure (p < 0.005).
      However, with celiprolol heart rate at rest was significantly less depressed then
      with atenolol (p = 0.004) and showed a distinctly less pronounced depression of
      heart rate with exercise (p = 0.004). Cardiac output at rest was reduced by 19%
      under atenolol, but was increased by 9% under celiprolol treatment; in this
      respect, the two medications differed significantly (p = 0.03). The adaptation of
      heart rate and cardiac output to exercise was better with celipropol as compared
      to atenolol treatment. The difference between arm arterial pressure and ankle
      occlusion pressure at rest was not significantly influenced by atenolol, whereas
      celiprolol treatment increased this difference by a mean of up to 16 mmHg (p =
      0.009). This different effect on peripheral arterial circulation was even more
      pronounced after exercise. Both celiprolol and atenolol increased blood cell flow
      velocity in the nailfold capillaries, but this increases was statistically only
      significant with celiprolol (p = 0.047). These results demonstrate that the
      hemodynamic effects of celiprolol were significantly different from those of
      atenolol; celiprolol produces less bradycardia, increases cardiac output at rest
      and decreases peripheral arterial resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8573225
TI  - Effect of loratadine on immediate and delayed type hypersensitivity reactions.
AB  - Loratadine (CAS 79794-75-5) was effective in inhibiting the contractions of the
      ileum induced by histamine in guinea pigs. The drug also caused an anti
      acetylcholine, anti-serotonin and anti-leukotriene D4 (LTD4) effect. In addition,
      loratadine inhibited the synthesis of leukotrienes more potently than ketotifen.
      On the other hand, in in vitro studies of histamine release from rat peritoneal
      mast cells induced by compound 48/80 or lung fragments in actively sensitized
      guinea, pigs, loratadine elicited a significant inhibition at a concentration of
      5 mumol/l. In ex vivo studies, the drug inhibited histamine release from lung
      fragments induced by concanavalin A, and significant effect lasted for 24 h when
      the drug was administered at a dose of 20 mg/kg. The drug inhibited LTD4 release
      as well as histamine from lung fragments in actively sensitized guinea pigs.
      Loratadine inhibited not only 45Ca uptake into the rat peritoneal mast cells but
      also Ca2+ release from the intracellular Ca store induced by compound 48/80 or
      A23187. Loratadine increased cAMP content in rat lung preparation while
      decreasing cGMP content. Loratadine caused no significant change in order
      parameter and phospholipase A2 activity. The drug was more potent than ketotifen
      and terfenadine in inhibiting antigen-induced increase in airway resistance in
      guinea pigs. In addition, the effect of loratadine on airway resistance was
      sustained for 12 h. Loratadine inhibited an increase in dye leakage into the
      nasal cavity in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8573226
TI  - Analgesic activity of the lysozyme peptide N-(N-L-threonyl-L-alpha-aspartyl)-L
      tyrosine in the monkey and the dog.
AB  - N-(N-L-Threonyl-L-alpha-aspartyl)-L-tyrosine (CAS 115053-54-8, SPA-S-646) was
      originally derived from lysozyme. It has previously been found to have analgesic
      properties following oral and intravenous administration to laboratory rodents.
      In the rhesus monkey, intramuscular administration of SPA-S-646 caused a dose
      related analgesia. This effect was not seen following oral administration, but
      when given via the rectum, analgesia was again observed. In the dog, a single
      dose of 50 mg/kg was active by the intramuscular route but not the oral route. It
      is thought that unlike the rat, the digestive systems of the rhesus monkey and
      the dog degrade the tripeptide into inactive constituents.

PMID- 8573227
TI  - Effect of nitrovasodilators on the rhythmic contractions of guinea-pig isolated
      sphincter of Oddi.
AB  - The effects of amyl nitrite (CAS 8017-89-8) isosorbide dinitrate (CAS 87-33-2)
      and sodium nitroprusside (CAS 14402-89-2), on the acetylcholine-induced
      tachyrhythmia (greater than 9 waves/min) were investigated in the isolated guinea
      pig sphincter of Oddi. Acetylcholine (10(-3) mol/l) produced an initial rapid
      rise in tension, the peak being followed by a gradual decrease associated with
      the initiation of the peristaltic waves. Nitrovasodilators significantly
      decreased the initial response to acetylcholine. Methylene blue (5 x 10(-5)
      mol/l), a soluble guanylate cyclase inhibitor, increased the tonic response to
      acetylcholine and reversed the inhibition caused by nitrovasodilators. The
      frequency and amplitude of peristaltic waves were decreased by nitrovasodilators.
      Methylene blue significantly increased both the frequency and amplitude of
      peristaltic waves, however, it did not reverse the inhibition caused by
      nitrovasodilators tested. Results suggest that nitrates decrease the
      acetylcholine-induced contraction and peristaltism of isolated guinea-pig
      sphincter of Oddi and NO released by acetylcholine may partially suppress its own
      tonic contractile response.

PMID- 8573228
TI  - Physico-chemical properties and biological activities of erythromycin nalidixate.
AB  - Erythromycin nalidixate was prepared by combining nalidixic acid with
      erythromycin base. Thin-layer chromatographic studies and infrared absorption
      spectrum confirmed homogeneity of the new salt. The salt is very soluble in
      nonpolar solvent and freely soluble in polar solvent. The salt is quite stable at
      room temperature (30 +/- 1 degrees C). The antimicrobially active dose of the
      salt was found to be 820 micrograms/mg. Serum protein binding amounted to 85% and
      was reversible. LD50 in mice was found to be 371.5 mg/kg when the intraperitoneal
      route was used.

PMID- 8573230
TI  - Comparison of the in vitro activity of fluconazole against Candida albicans and
      dermatophytes.
AB  - Fluconazole (CAS 86386-73-4, Diflucan, Fungata is an antimycotic agent of
      established value in the treatment of systemic infections with yeasts; more
      recently this drug has been used in the oral treatment of dermatomycoses. The in
      vitro activity of fluconazole against 51 strains of C. albicans and 207 isolates
      of four different species of dermatophytes was therefore measured and the results
      collated. The mean minimal inhibitory concentrations (MIC) show that in vitro
      fluconazole is a significantly stronger inhibitor of the proliferation of C.
      albicans (0.34 micrograms/ml) than of the dermatophytes T. rubrum (6.4
      micrograms/ml), T. mentagrophytes (23.9 micrograms/ml), M. canis (18.3
      micrograms/ml) and E. floccosum (3.5 micrograms/ml). On the other hand, the
      distribution of the MIC values shows that the sensitivity to fluconazole within a
      single species is also very variable. It is evident that the concentrations of
      fluconazole reached particularly in the stratum corneum of the skin after oral
      therapy are adequate to inhibit the growth of the yeasts and of the dermatophytes
      examined.

PMID- 8573229
TI  - Modulation of luminol-dependent chemiluminescence of murine macrophages by
      flavone and its synthetic derivatives.
AB  - The effect of flavone (CAS 525-82-6, 2-phenylbenzopyran-4-one, 1), flavone-8
      acetic acid (CSA 87626-55-9, FAA, 2) and 10 substituted flavones on the luminol
      dependent chemiluminescence of murine macrophages was studied in vitro. The
      synthetic derivatives were variously substituted with halo, nitro, amino, hydroxy
      and methoxy substituents in the 3' and 4' positions. Chemiluminescence was used
      in this study as an indicator for the production of reactive oxygen species by
      macrophages, stimulated in vitro by phorbol myristate acetate (PMA). All flavones
      except FAA (2) showed more than 20% inhibition at 10 mumol/l or 100 mumol/l. 3'
      Amino-4'-hydroxyflavone (8) was the most potent inhibitor. The IC50s for
      inhibition of chemiluminescence were 4.2 +/- 1.1 mumol/l, 5.0 +/- 1.0 mumol/l and
      3.3 +/- 1.4 mumol/l for resident, elicited and LPS-Poly I:C-primed macrophages,
      respectively. Small but statistically significant enhancements of
      chemiluminescence were caused by low concentrations of flavone (1), FAA (2) and
      4'-methoxyflavone (6). These results suggest that modulation of the
      chemiluminescent capacity of macrophages depends on the nature of the
      substituents and the concentration of the flavones.

PMID- 8573231
TI  - Effects of furosemide, captopril and indometacin on the renin-angiotensin system
      and the renal prostaglandins in anesthetized neonatal piglets.
AB  - The effects of the diuretic furosemide (CAS 54-31-9) 1 mg/kg bw i.v., of the
      angiotensin converting enzyme (ACE) inhibitor captopril (CAS 62571-86-2) 1 mg/kg
      bw p.o. and the prostaglandin synthesis inhibitor indometacin (CAS 53-86-1) 2
      mg/kg bw p.o. on kidney function, salt and water excretion, the excretion of
      renal prostaglandins PGE2, PGF2a, 6-keto-PGF1a, thromboxane B2 (TXB2) and the
      plasma renin activity (PRA) were investigated on 29 neonatal piglets. Within 1 h,
      fuorsemide led to pronounced diuresis and natriuresis, to a rise of the
      glomerular filtration rate (GFR) (which ist low in neonatal pigs) by 1.8 times,
      increased the excretion of renal prostaglandins (especially the vasoconstrictor,
      thromboxane B2 (TXB2 and PGF2a) and raised the PRA significantly. Under
      captopril, the PRA rose significantly, whereas there was no unequivocal change in
      the excretion of renal prostaglandins. There was a pronounced decline of the
      sodium and potassium excretion in the urine with a fall in the concentrations of
      electrolytes in serum and of the hematocrit. Under indometacin, the excretion of
      all prostaglandins in the urine declined (this decline was most pronounced for
      PGE2). There was also a decrease in sodium excretion, whereas there was no
      significant change in PRA. It can be concluded from the results that the effects
      of the investigated drugs on the pig neonate kidney is at least partially
      attributable to an influence on hormonal factors.

PMID- 8573232
TI  - Changing childbirth: for better and for worse.

PMID- 8573233
TI  - Classifying meconium-stained liquor: is it feasible?
AB  - Four samples each of clear and lightly (thin), moderately, and heavily (thick)
      meconium-stained amniotic fluid were divided in two portions and submitted twice
      for assessment to 20 midwives (a total of 320 case assessments). None of the
      midwives completely agreed with the standard assessment for more than 85 percent
      of the cases. When disregarding clear samples, for which there was good
      agreement, each of the midwives classified on average only 35.8 percent of the
      meconium-stained samples in the same category on each of the four occasions that
      they were presented to them. Calculation of kappa statistics, which express
      proportional agreement corrected for chance, indicated that none of the midwives
      showed very good agreement (kappa > 0.81) with the standard and that fewer than
      10 percent showed very good agreement with themselves. The data indicate that
      grading the severity of meconium staining by visual assessment has such poor
      accuracy and precision that it cannot provide a valid basis for assigning
      different care policies to different degrees of meconium staining.

PMID- 8573234
TI  - Mothers touching newborns: a comparison of rooming-in versus minimal contact.
AB  - We compared the maternal behaviors of women who had extended and early contact
      (rooming-in) with their infants with those who had contact only during feedings.
      Thirty-one young, unmarried, predominantly black, lower-socioeconomic mothers and
      their infants were observed in the mother's hospital room for 15 minutes after a
      morning feeding approximately 18 hours after delivery. A time sample unit
      checklist was used to record each mother's behavior, looking, talking, and
      touching directed toward their infants and others, as well as watching television
      and talking on the telephone. Analyses of variance revealed that the rooming-in
      mothers looked at, talked to, and touched their infants more, watched less
      television, and talked less on the telephone than mothers with minimal contact
      with their infants. These findings suggest that increased postpartum contact with
      infants leads not only to more interaction, but also to more touching as well as
      touching in more intimate places (face and head), thus highlighting the value of
      rooming-in arrangements for mothers and infants.

PMID- 8573235
TI  - Hmong women in Wisconsin: what are their concerns in pregnancy and childbirth?
AB  - Childbirth in different cultures is treated as a traumatic life crisis and a time
      of vulnerability for the mother and infant. This qualitative descriptive study
      explored specific concerns related to pregnancy and childbirth in 52 Hmong women
      living in central and northeastern Wisconsin. Women were questioned using a
      semistructured interview about 4.6 months after childbirth. They described
      concerns related to breastfeeding, contraception, touch, communication with
      health caregivers, and procedures performed during childbirth. Women preferred
      bottle-feeding over breastfeeding. They reported difficulty practicing birth
      control because of cultural expectations of male and female roles, but were aware
      of the need for education about methods of contraception. Fear of miscarriage if
      they were touched by doctors and nurses resulted in delayed prenatal visits. The
      women believed that invasive procedures such as episiotomies and circumcisions
      are not natural, and they preferred natural tearing and healing. It is important
      for health caregivers to be culturally sensitive and understanding of Hmong
      practices and beliefs when touching and communicating with these women and when
      educating them about breastfeeding, contraception, and medical procedures during
      hospitalization.

PMID- 8573236
TI  - Cesarean delivery rates in women cared for by certified nurse-midwives in the
      United States: a review.
AB  - The frequency of cesarean deliveries for women attended by certified nurse
      midwives in the United States (1.8-10.4%) is lower than the rate for the general
      population of woman who gave birth in the United States in 1990 (23%). This paper
      describes the research that reported cesarean birth rates for certified nurse
      midwives. Major methodology limitations of the research suggest that significant
      information gaps exist regarding nurse-midwifery care and its effect on cesarean
      delivery. Issues surrounding this common clinical procedure are complex, with its
      high cost and controversy over determinant factors. It is important to develop
      convincing evidence about the influence of nurse-midwives' care on reducing the
      frequency of cesarean delivery in the United States.

PMID- 8573237
TI  - Denial of pregnancy: a review and case reports.
AB  - This paper describes the characteristics of women who deny awareness of their
      pregnancies, the underlying causes and conflicts, and specific interventions
      required to address these issues. Case reports illustrate this complication of
      pregnancy. The absence of many physical symptoms of pregnancy, inexperience,
      general inattentiveness to bodily cues, intense psychological conflicts about the
      pregnancy, and external stresses can contribute to the denial in otherwise well
      adjusted women. Assessment should include the possible contribution of painful
      reactivation of memories concerning childhood or adult trauma and the effect of
      dissociative states on the development of denial of pregnancy. Psychotherapy is
      recommended to resolve these conflicts, and to prevent future pregnancy denials
      and child abuse or neglect. Denial of pregnancy is easier to understand in women
      with psychosis or serious cognitive impairment than in those without such
      disorders. The underlying illness requires treatment by a psychiatrist.
      Psychological conflicts also exist in psychotic women, such as the intense wish
      to have a baby while fearing loss of the infant to child-protection services.
      Acknowledging the conflict and supporting the mother despite her puzzling
      behavior is an important task for health caregivers.

PMID- 8573238
TI  - Change and power in midwifery.
AB  - Midwives are experiencing problems in playing their full part in the maternity
      services and the communities in which they practice. Mothers, babies, and
      families require greater care from these caregivers for healthier pregnancy and
      birth outcomes. Change to renew the power, skills, and knowledge of midwives is
      evident in many parts of the world. Processes of change require an examination of
      the purpose of midwifery. The starting point of change is an awareness of the
      meaning of birth to individuals and society, and of the role of midwives in
      supporting families around the time of birth. Midwives should use their power to
      resolve the considerable problems facing childbearing families, and to enrich the
      event.

PMID- 8573239
TI  - "Family physician and maternity care: high tech or high touch?

PMID- 8573240
TI  - Nitric oxide synthase in cerebral ischemia. Possible contribution of nitric oxide
      synthase activation in brain microvessels to cerebral ischemic injury.
AB  - The results of our continuing studies on the role of nitric oxide (NO) in
      cellular mechanisms of ischemic brain damage as well as related reports from
      other laboratories are summarized in this paper. Repetitive ip administration of
      NG-nitro-L-arginine (L-NNA), a NO synthase (NOS) inhibitor, protected against
      neuronal necrosis in the gerbil hippocampal CA1 field after transient forebrain
      ischemia with a bell-shaped response curve, the optimal dose being 3 mg/kg.
      Repeated ip administration of L-NNA also mitigated rat brain edema or infarction
      following permanent and transient middle cerebral artery (MCA) occlusion with a U
      shaped response. The significantly ameliorative dose-range and optimal dose were
      0.01-1 mg/kg and 0.03 mg/kg, respectively. Studies using a NO-sensitive
      microelectrode revealed that NO concentration in the affected hemisphere was
      remarkably increased by 15-45 min and subsequently by 1.5-4 h after MCA
      occlusion. Restoration of blood flow after 2 h-MCA occlusion resulted in enhanced
      NO production by 1-2 h after reperfusion. Administration of L-NNA (1 mg/kg, ip)
      diminished the increments in NO production during ischemia and reperfusion,
      leading to a remarkable reduction in infarct volume. In brain microvessels
      obtained from the affected hemisphere, Ca(2+)-dependent constitutive NOS (cNOS)
      was activated significantly at 15 min, and Ca(2+)-independent inducible NOS
      (iNOS) was activated invariably at 4 h and 24 h after MCA occlusion. Two hour
      reperfusion following 2 h-MCA occlusion caused more than fivefold increases in
      cNOS activity with no apparent alterations in iNOS activity. Thus, we report here
      based on available evidence that there is good reason to think that NOS
      activation in brain microvessels may play a role in the cellular mechanisms
      underlying ischemic brain injury.

PMID- 8573241
TI  - Effects of chronic ethanol exposure on cultured cerebellar granule cells.
AB  - The aim of this study was to investigate the lipid content and composition of rat
      cerebellar granule cells grown in the presence of ethanol (40, 55, or 80 mM)
      during in vitro differentiation. Quantitative analyses showed no effects of 40 mM
      ethanol, whereas a significant increase of total cholesterol was observed at 55
      mM. Cells exposed to the highest ethanol dose (80 mM) were characterized by a
      higher sialidase activity, and by the modification of the ganglioside pattern and
      phospholipid fatty acid composition. The observed modifications were accompanied
      by changes of membrane anisotropy fluorescence assessed by the fluorescent probe
      1,6-diphenyl-1,3,5-hexatriene.

PMID- 8573242
TI  - Early hypothalamic activation of combined Fos and CRH41 immunoreactivity and of
      CRH41 release in push-pull cannulated rats after systemic endotoxin challenge.
AB  - We previously showed that intra-arterial endotoxin infusion (lipopolysaccharide
      [LPS]: 25 micrograms.kg-1) induced an early (15 min) and sustained (480 min) rise
      in plasma ACTH associated with delayed (60-120 min) increases in plasma
      concentrations of TNF alpha, IL-6, and IL-1 beta. In the present study, we
      followed the post-LPS time-course of immunocytochemical expression of Fos-like
      activity in CRH41 neurons whose immunolabeling was enhanced by icv colchicine
      pretreatment 48 h before the LPS, and CRH41 release in the push-pull cannulated
      median eminence of free-moving rats, in parallel with the ACTH response. The
      earliest Fos-like activity in IR-CHR41 neurons was detected 30 min post-LPS.
      Colchicine strongly inhibited the LPS-induced activation of Fos expression in
      single-labeled paraventricular neurons. CRH41 release in the median eminence
      displayed a biphasic stimulation pattern, with a first peak (+60%) at 15 min
      together with the ACTH surge, followed by a second rise beginning at 45 min and
      lasting more than 2 h. Thus, the early stage of the ACTH surge following a
      nonlethal endotoxin challenge (< 60 min) already involves the activation of CRH41
      producing neurons.

PMID- 8573243
TI  - Changes in serotonin-immunoreactivity in the dorsal and median raphe nuclei of
      rats exposed to 2,4-dichlorophenoxyacetic acid through lactation.
AB  - Comparison of serotonin-immunoreactive (SER-IR) neurons in nucleus raphe dorsalis
      (NRD) and median raphe nucleus (MRN) of 25-d-old rat pups exposed to 70 mg/kg/d
      2,4-dichloro-phenoxyacetic acid through mothers milk and control pups was made
      using an immunohistochemical analysis. Significant 2,4-D-treatment-related
      increase in size and density of SER-IR neuronal somata as well as in fiber length
      were observed. We postulate that exposure to 2,4-dichlorophenoxyacetic acid on
      the first day of life would modify the synthesis of 5-HT or the maturation of the
      brain serotonergic system.

PMID- 8573244
TI  - Age-dependent susceptibility of CNS glial populations in situ to the
      antimetabolite 6-aminonicotinamide.
AB  - Intraperitoneal injections of the nicotinamide antagonist 6-amino-nicotinamide (6
      AN) were used to determine if there are regional differences in putative glial
      energy metabolism between the developing and adult rat CNS. 6-AN shuts down the
      hexose monophosphate pathway, which is used preferentially by astrocytes and
      oligodendrocytes. These cells subsequently undergo cytotoxic edema and cell
      death. Adult rats and pups ranging in age from 7 to 31 d received a single
      injection of 6-AN and were sacrificed after 24 h. As demonstrated wit
      immunocytochemical staining for the astroglia-specific markers GFAP and S-100
      beta, the 7-9-d-old animals exhibited a uniform appearance with edematous glial
      cells located throughout the CNS. However, with advancing age, a consistent
      pattern of progressively decreasing amounts of injured glia, which has not been
      previously described, occurred in cerebral and cerebellar structures. After 3 wk
      postnatal, the adult pattern was manifested in which glial degeneration occurred
      only in specific regions of the spinal cord, cerebellum, medulla, and thalamus,
      whereas the remainder of the CNS appeared normal. The results suggest the
      presence of heterogeneous populations of glia whose preferred use of the hexose
      monophosphate pathway is predicated on both the age of the animal and their
      location in the CNS.

PMID- 8573245
TI  - Age-dependent effects of t-BuOOH on glutathione disulfide reductase, glutathione
      peroxidase, and malondialdehyde in the brain.
AB  - Intracerebroventricular t-butyl hydroperoxide has been reported to induce damage
      to many types of brain cells. t-Butyl hydroperoxide administration increases
      glutathione disulfide levels and decreases levels of glutathione. Young adult
      mice may be more protected from t-butyl hydroperoxide than mature mice due to
      their higher glutathione levels, even after the administration of t-butyl
      hydroperoxide. This leads to our current study, investigating glutathione
      peroxidase and glutathione disulfide reductase in 2-mo-old and 8-mo-old mice.
      Furthermore, malondialdehyde levels were measured with the thiobarbituric acid
      assay and compared between the two age groups. Mature mice detoxify glutathione
      disulfide less readily than young adult mice. Glutathione disulfide reductase
      activity increases in young adult mice after t-butyl hydroperoxide
      administration, but not in mature mice. Glutathione peroxidase activity is
      significantly lower in 8-mo-old than 2-mo-old mouse striatum after t-butyl
      hydroperoxide administration. Furthermore, malondialdehyde levels in the 8-mo-old
      striatum increase significantly 20 min after t-butyl hydroperoxide
      administration. This suggests that age plays a factor in protective mechanisms
      that are involved in oxidative stress in the brain.

PMID- 8573246
TI  - [Urological management of renal transplant patients].

PMID- 8573247
TI  - [Anesthetic management of the anephric patient].

PMID- 8573248
TI  - Clinical and experimental immunosuppression.

PMID- 8573249
TI  - [Outcome of pregnancy in patients with transplants with and without cyclosporin
      therapy].

PMID- 8573250
TI  - [Crucial role of education of transplant patients].

PMID- 8573251
TI  - [Social evaluation and the noncompliance problem].

PMID- 8573252
TI  - [Hyperlipidemia in patients with kidney transplant: causes, effects and
      management].

PMID- 8573253
TI  - [Advances of immunobiology].

PMID- 8573254
TI  - [500 renal transplants in Puerto Rico].

PMID- 8573255
TI  - [The first 500 renal transplants in Puerto Rico].

PMID- 8573256
TI  - [Organ donation: National (USA) and local (P.R.) problem].

PMID- 8573257
TI  - [Discordance between knowledge and attitudes among health professionals
      concerning organ donation].

PMID- 8573258
TI  - [Experience with unrelated live donors in Puerto Rico].

PMID- 8573259
TI  - [Organ transplantation and Christian ethics].

PMID- 8573260
TI  - [Hospital, a central pivot of a transplantation program].

PMID- 8573261
TI  - [Intestinal helminthiasis in the Mexican Republic].
AB  - Very few uncertain and not trustworthy reports about the frequency of intestinal
      helminthiases found in humans have been made in Mexico. However, with the few
      trustful studies carried out from 1981 to 1992, it is possible in Mexico to
      verify that ascariasis, trichuriasis, hookworm infection and hymenolepiasis are
      present with significant percentages of infected people 11.2%, 1.7%, 0.15% and
      1.8%, respectively. With the information obtained from the researches analyzed in
      this article, one can conclude that human infections by intestinal helminths in
      Mexico, at the present time are almost as frequent as in past decades. Without
      any doubt, this occurs because still remain the factors that contribute to the
      persistence and spreading of the intestinal helminths, such as fecalism, poor
      hygienic and alimentary habits within deficient environmental sanitary
      conditions.

PMID- 8573262
TI  - [Housedust mites++ in the city of Valdivia, Chile].
AB  - In the house dust there are different species of mites, which have medical
      importance because they are related to allergic asthma, rhinitis and/or
      dermatitis. Between april-august 1989 and march-june 1990, 100 samples of house
      dust collected in the city of Valdivia, Chile were analyzed. By using special
      techniques the samples were examined and classified. In the present research 70
      samples of dust were positive, which showed one or more species of mites.
      Thirteen species and one genus were classified. The average quantity of house
      dust examined by sample was 0.69 g and a total of 701 mites were isolated, being
      identified 691 of them: Glycyphagus destructor (23.4%), G. domesticus (22.7%),
      Blomia tjibodas (19.2%), Cheyletus eruditus (6.5%) and Chortoglyphus arcuatus
      (12.0%), were the most frequent species found. In 74.2% of the positive samples
      two or more species of mites were observed, being the most common the association
      of two species, with the combinations: G. destructor-G. domesticus; G. domesticus
      Tyrophagus putrescentiae; G. destructor-Ch. eruditus.

PMID- 8573263
TI  - [Contracaecum sp. larvae (Nematoda, Anisakidae) infection in Salminus maxillosus
      (Pisces, Characidae) in the dam of Termas de Rio Hondo, Argentina].
AB  - Between 1992 and 1993, ten characid fishes, Salminus maxillosus from Termas de
      Rio Hondo pond (27 degrees 33' S 64 degrees 57' W), Argentina were examined for
      Contracaecum sp. infection. Larvae were isolated from peritoneum of intestine and
      piloric ceca of salmonids. Morphological characteristics of larvae are described
      with optical microscopy and scanning electron microscopy. Morphological
      comparisons between Contracaecum sp. from S. maxillosus, and Contracaecum
      rudolphii from freshwater fishes species from Southern Chile and Argentina are
      given.

PMID- 8573264
TI  - Description of a new species of the genus Raphidascaroides Yamaguti, 1941
      (Nematoda: Heterocheilidae (from the shark, Sphyrna ztgaena (Linnaeus) at
      Visakhapatnam, India.
AB  - A new species of the nematode genus Raphidascaroides Yamaguti, 1941 obtained from
      the intestine of hammer-headed shark, Sphyrna zygaena (Linnaeus) from
      Visakhapatnam is described. The specimens do not agree with the description of
      known species of the genus. Raphidascaroides zygaenai has been established by
      body size, length of oesophagus and oesophageal appendix, size of spicules,
      number and arrangement of caudal papillae, vulva position and structure of tail
      end.

PMID- 8573265
TI  - [Larval trematodes (Digenea) of Diplostomidae, Strigeidae and Echinostomatidae
      families in the Patagonian Region in Argentina].

PMID- 8573266
TI  - [Levels of anti-Gal antibodies in persons infected and non-infected with
      Trypanosoma cruzi. Probably induced by bacteria and by the parasite].
AB  - Antibodies levels against Gal alpha 1,3 Gal epitopes were studied in 407 human
      sera (92 chagasic and 315 non-chagasic), by means of hemagglutination with rabbit
      erytrocytes reactivity of serum having high titres of anti-Gal antibodies in
      presence of Escherichia coli and Serratia marcescens antigen was studied by
      immunoelectrotransference. Finally, using a purified anti-Gal antibody, Gal alpha
      1,3 Gal epitopes were identified in metacyclic forms from 12 high Andean Chilean
      strains of Trypanosoma cruzi. Among the chagasic sera, it was demonstrated that
      in 63 (68.5%) were detected antibodies anti-Gal at the same or higher titer than
      1:1,600; while i the non chagasic sera only 49 (15.6%) showed and anti-Gal
      response at similar titers. Immunoelectrotransference showed that the sera of
      people infected with T. cruzi recognize antibodies present in E. coli and S.
      marcescens, which reinforces the idea that at least in part, these bacterias
      would be capable of stimulating these responses. The autoradiographic analysis
      using purified anti-Gal antibodies, showed differences in the Gal alpha 1,3 Gal
      epitopes expressed in the different strains of T. cruzi. These results suggest
      that anti-Gal antibodies could have a real significance on the natural immunity
      mechanisms and protection of human infection with T. cruzi.

PMID- 8573267
TI  - [Larval stages of digenetic trematodes in Chilina sp. (Mollusca, Pulmonata) of
      some water bodies of Patagonia, Argentina].
AB  - Chilina sp., found abundantly in Patagonian fresh water bodies, is an
      intermediate host in the biological cycles of several digenetic trematodes.
      Larvae at different developmental stages were found in the visceral mass of
      snails collected from several places, and were determinated to family level. This
      work shows these findings, with presence and prevalence data, and so attempts to
      contribute to increase the parasitological knowledge about studied water bodies.

PMID- 8573268
TI  - [Hydatidosis of the humerus complicated with fracture, bacterial infection,
      fistula, and extraosseous localization].
AB  - The clinical case of an apparently healthy 63-year-old man from a rural area,
      with previous contact with dogs, who had a pathological fracture of the right
      humerus is presented. Initially he presented slight local pain, and functional
      discapacity. Eight months later, after a radiological study and surgery
      (curettage), diagnosis of hydatid disease was made. Later on, after receiving two
      courses with albendazole, the parent continued in similar conditions for seven
      years, when his situation became complicated with bacterial, fistula and
      extraoseous hydatidosis. The humerus was resected and a segmentary prothesis was
      successfully set.

PMID- 8573269
TI  - [Positivity of xenodiagnosis, according to age, in persons with positive serology
      for Chagas disease].
AB  - An analytical study of positive xenodiagnosis (XD), according to age
      distribution, in people with a positive indirect hemagglutination test (IHAT) for
      Chagas' disease has been carried out. A total of 1,137 IHAT for Chagas' disease
      positive persons were submitted to two wooden XD boxes containing 7 Triatoma
      infestans nymphs III each. The positivity (%) of XD in the different age groups
      was: 0-9 year-old (60.8), 10-19 (35.8), 20-29 (31.5), 30-39 (28.7), 40-49 (30.0),
      50-59 (34.3) and > or = 60 (43.3). The 60.8% positivity of XD in children under
      10 years of age is possibly due to the rather recent Trypanosoma cruzi infection
      in this age group and to diverse immunological mechanisms, which decrease with
      the age increasing.

PMID- 8573270
TI  - [Chagas disease in northern Chile. Serological prevalence in pregnant women of
      the city of Antofagasta, 1991-1993].
AB  - Antofagasta, the big city-port in North Chile is a triatomines free locality.
      Chagas infection was serologically diagnosed in 44 out of 2063 (2.1%) pregnant
      women from Antofagasta, studied by means of an indirect immunoflourescence test
      (IIFT), during 1991-1993. Out of the 44 seropositive mothers, 31 and 10 were born
      in the II (moderate endemic area) and IV Region (hiperendemic area),
      respectively. The usefulness of a screening programme for congenital Chagas'
      disease at primary health care in Chile is discussed.

PMID- 8573271
TI  - A qualitative approach to the evaluation of a cardiac education follow-up
      program.
AB  - The purpose of this study was to evaluate a Cardiac Education Follow-Up Program
      from the consumer's perspective. Nine cardiac patients between the ages of 51 and
      70 participated. All had diagnoses of myocardial infarction and had taken the
      Program within the previous month. Patton's (1986) utilization-focused approach
      to evaluation provided the conceptual orientation and the Davis Patient Interview
      Guide (DPIG) was used for data collection. Results indicated that four aspects of
      the Program were of predominant interest/concern: information; support; the
      cardiologist's session; and the room in which the class was offered.
      Recommendations for program modification, using the results of the consumer's
      evaluation, are identified.

PMID- 8573272
TI  - Two very different uses of the qualitative research method.

PMID- 8573274
TI  - Patient outcomes research: Part III.

PMID- 8573273
TI  - Nursing criteria for patient progression post myocardial infarction.
AB  - Nurses play a pivotal role in the evaluation of patients with coronary artery
      disease, since many symptoms are subtle and arise while carrying out activities.
      Consistency among nursing staff in interpreting patient readiness for activity is
      crucial to ensure that patients are progressing steadily or to determine if a
      delay in their progression is warranted. While there have been studies on patient
      reaction to myocardial infarction and on the physiological effects of activity
      and/or nursing interventions on myocardial patients, no studies could be found
      that have examined the criteria used by nurses to assess when patients are ready
      to increase, decrease or maintain a level of activity according to specific
      activity protocols. This descriptive study examined the criteria utilized by
      experienced staff nurses in determining post myocardial patients' readiness to
      progress through the institution's designated activity levels. The results
      indicated that in-depth criteria were utilized by these experienced nurses and
      that patient situations existed whereby it was difficult to determine patient
      readiness. Factors were discovered that were perceived to enhance or inhibit
      patient's progression through designated activity levels. Recommendations from
      this study support the need to (a) examine the use of current activity protocols
      for their utility in nursing decision making, (b) consider the experiential base
      of practicing nurses as well as the working environment in any further
      development of activity protocols.

PMID- 8573275
TI  - What the members say: CCCN membership survey 1995.

PMID- 8573276
TI  - Femoral arterial sheath removal after PTCA: a cross-Canada survey.
AB  - A cross-sectional survey was conducted to examine current Canadian practices in
      the nursing and medical management of femoral arterial sheath removal (SR) after
      PTCA (percutaneous transluminal coronary angioplasty). The purposes of the study
      were to (a) investigate the roles of the nurses and physicians in SR, (b) assess
      the length of time arterial sheaths are left in place and patients kept on
      bedrest, and (c) describe the routine medical protocols used for pain and
      anticoagulation therapy. Of the 35 hospitals that perform PTCA in Canada, 30
      responded to the survey (response rate of 86%). Nurses had primary responsibility
      for SR in 13% of the sites and shared responsibility with physicians for SR in a
      further 10% of the institutions. When nurses were trained to remove sheaths, they
      assumed responsibility for the adjunctive steps to establish hemostasis. One
      third of hospitals removed sheaths in 4 hours or less; approximately 75% of them
      removed sheaths in 6 hours or less after PTCA. Patients are kept on bedrest for 6
      hours or less following hemostasis in half, and 8 hours or less at three-quarters
      of the hospitals. Post-PTCA and pre-SR anticoagulant monitoring was used in
      almost half of the sites. Premedication for SR varied from no premedication to
      combinations of three intravenous medications plus local anaesthetic. Survey
      results showed that in almost one quarter of the Canadian institutions where PTCA
      is performed, nurses play a role in SR. Results also showed that there is no
      uniformity in post-PTCA SR across Canada and that further research is needed to
      identify the optimum approach to managing this common cardiovascular procedure.

PMID- 8573277
TI  - The Nursing Research Fellowship Program: problems and recommended changes.

PMID- 8573278
TI  - Comparisons of pulmonary artery pressure measurements in supine and 30 degree
      lateral positions.
AB  - The purpose of this study was to compare the effects on pulmonary artery pressure
      (PAP) measurements of using different anatomical reference points for transducer
      placement. Supine and 30 degree right and left lateral PAP measurements were
      examined in a sample of 40 hemodynamically stable post-cardiovascular surgery
      patients. The anatomical references for transducer placement were (a) the supine
      phlebostatic axis, (b) the right lateral phlebostatic axis, and (c) the mid
      sternum at the fourth intercostal space. The results of analysis of variance
      procedures for repeated measures showed lateral compared to supine PAP
      measurements differed significantly regardless of the anatomical reference used
      for the transducer placement (p = < .0001). Clinically insignificant differences
      in supine and lateral PAP measurements were shown when the transducer reference
      was the supine phlebostatic axis. Use of the right lateral phlebostatic axis and
      the mid-sternum did result in clinically significant changes in lateral compared
      to supine PAP measurements. Implications for research and for clinical practice
      are discussed.

PMID- 8573279
TI  - [New approach for defibrillation after cardiac reoperation].
AB  - Cardiac reoperations are associated with several complications such as
      ventricular lacerations, major vessel trauma, and ventricular arrhythmias. As it
      is impossible to defibrillate before ending the pericardial dissection, this
      latter complication increases the mortality rate in the perioperative period. In
      those instances, the self-adhesive electrode pads for external defibrillation
      were proven effective for cardioversion and defibrillation, even in the presence
      of adherences. In our institution, these electrode pads are compulsory for all
      patients requiring cardiac reoperation. The apex pad covers the cardiac apex in
      the V5 and V6 electrode derivations, while the posterior pad is placed over the
      right infrascapular area, which reduces the risk of hazardous current
      concentration. In addition, it does not obstruct the operative site and the pads
      can be connected to a R2 cable adaptor compatible with regular leading
      defibrillating systems. The electrode pads were tested on 132 of the 508 patients
      (26%) requiring cardiac surgery during a 6-month period. Eighteen of these cases
      (14%) required one or more defibrillating during the operation. The benefits of
      using this system (R2 Corporation, Skokie, Ill) include: a smaller dissection,
      reduced blood loss, lower numbers of blood transfusions, and decreased operating
      time. When the electrode pads remain in place during the patient's transfer to
      the intensive care unit and the first hours thereafter, they can be used again
      this time to control arrhythmia complications after the surgery.

PMID- 8573280
TI  - Amylolytic enzymes and products derived from starch: a review.
AB  - This review provides current information on starch and its molecular composition,
      common and potential sources, and manufacturing processes. It also deals with the
      five groups of enzymes involved in the hydrolysis of starch: the endo- and
      exoamylases, which act primarily on the alpha-1,4 linkages; the debranching
      enzymes, which act on the alpha-1,6 linkages; the isomerases which convert
      glucose to fructose; and the cyclodextrin glycosyltransferases which degrade
      starch by catalyzing cyclization and disproportionation reactions. This work
      mainly discusses the enzymatic processes for the manufacture of maltodextrins and
      corn syrup solids, including the production, both batch and continuous, of
      glucose syrup, and the processes to obtain sweeteners, such as maltose and 42,
      55, and 90% high-fructose corn syrups. It highlights the novel production of
      Schardinger's dextrins: the alpha-, beta-, and gamma-cyclodextrins, consisting of
      six, seven, and eight glucose monomers, respectively. New products are emerging
      on the market that can serve as fat and oil substitutes, moisture-retention
      compounds, crystal-formation controllers, stabilizers for volatile materials like
      flavors and spices, or products for the pharmaceutical industry. As a result,
      particular attention is given to functional properties and applications of the
      above-cited compounds.

PMID- 8573281
TI  - Lipid-based fat substitutes.
AB  - Fats and oils account for 38% of the total calories in the diet of Western
      populations, especially in the U.S. They provide the most concentrated source of
      energy, 9 kcal/g of a triacylglycerol molecule compared with 4 kcal/g provided by
      carbohydrate and protein. In response to consumer demands for low-calorie or
      calorie-free fats and their reluctance to give up the taste of fat, current
      research efforts have been directed toward the development of lipid-like fat
      substitutes. These fat substitutes contain the fatty acids found in conventional
      fats and oils, with all the physical and organoleptic properties of fats, but
      provide few or no calories in the diet. Some of the fat substitutes are modified
      triacylglycerols (glycerol backbone) with reduced digestion and absorption;
      others are digestible and nondigestible carbohydrate fatty acid esters and
      polyesters, respectively. Sucrose polyester (Olestra), a sucrose molecule
      esterified with six to either fatty acids, is the most studied of the lipid-based
      fat substitutes containing a carbohydrate backbone. If approved by the FDA,
      sucrose polyester will find application in almost all fat-containing foods.
      Specialty fats or fat substitutes targeted to certain individuals with special
      needs are being developed. Among these are the medium-chain triacylglycerols and
      structured lipids (glycerol backbone), or ?nutraceuticals? with reduced
      absorption and medical applications. Enzyme biotechnology is another tool
      available to lipid chemists to selectively modify, esterify, transform,
      transesterify, and interesterify fats and oils or synthesize new lipids such as
      structured lipids of food, nutritional, and medical importance. These designer
      fats may be the trend in the future to produce medical lipids that do not occur
      normally in nature. The different types of lipid-based fat substitutes are
      reviewed with respect to their synthesis, analysis, metabolism, potential
      applications/uses, and the future of fat substitutes.

PMID- 8573282
TI  - Value-added products from underutilized fish species.
AB  - Fish is a rich source of easily digestible protein that also provides
      polyunsaturated fatty acids, vitamins, and minerals for human nutrition.
      Nonetheless, a large proportion of total landed fish remains unused due to
      inherent problems related to unattractive color, flavor, texture, small size, and
      high fat content. Most of these underutilized fish belong to the abundantly
      available pelagic species, which are landed as bycatch, and some are
      unconventional species such as krill. Although some species are used industrially
      for fish meal manufacture, a need for their conservation and utilization for
      human consumption has been recognized in order to prevent post-harvest fishery
      losses. Recovery of flesh by mechanical deboning and development of value-added
      products are probably the most promising approaches. This article discusses
      various possibilities for product development using mince from low-cost fishery
      resources. These include surimi and surimi-based products, sausages, fermented
      products, protein concentrates and hydrolysates, extruded products, and
      biotechnological possibilities. The dual advantages of this approach, namely,
      finding ways for better utilization of low-value fish species and providing
      protein- rich convenience foods, have been pointed out. However, the key to the
      success of this approach depends largely on the market strategies utilized.

PMID- 8573283
TI  - Issues and advances in the use of transgenic organisms for the production of
      thaumatin, the intensely sweet protein from Thaumatococcus danielli.
AB  - The thaumatins are a class of intensely sweet proteins isolated from the fruit of
      the tropical plant Thaumatococcus danielli. Thaumatin is approved for use in many
      countries and has application as both a flavor enhancer and a high-intensity
      sweetener. The supply of naturally occurring thaumatin is limited, which has
      prompted extensive research into its synthesis via transgenic organisms. The gene
      encoding thaumatin has been introduced into various microorganisms under
      transcriptional control of heterologous promoters. Yields to date have been low,
      but the factors governing more efficient microbial production have been
      identified. Continued research should allow microbial yields to be improved to
      commercially viable levels. The unique properties of thaumatin as a food additive
      could well be exploited by the food industry. Alternatively, the thaumatin gene
      could be engineered directly into selected fruit and vegetable crops to improve
      their flavor and sweetness.

PMID- 8573284
TI  - Complement receptors in neutrophils.
AB  - Human neutrophils contain numerous intracellular granules and vesicles that are
      exocytosed in a hierarchic manner on stimulation of the neutrophil with
      inflammatory mediators. Secretory vesicles are mobilized completely to the plasma
      membrane when neutrophils are stimulated with inflammatory mediators in nanomolar
      concentrations. There is evidence that secretory vesicles contain at least four
      different complement receptors, namely, C1qR, CR1, CR3, and CR4. These complement
      receptors are all transported to the neutrophil surface in parallel by the
      mobilization of secretory vesicles. A fifth complement receptor, C5aR, is
      constitutively present on the neutrophil plasma membrane. Because secretory
      vesicles are mobilized by virtually all inflammatory mediators known to stimulate
      neutrophils, a prompt upregulation of complement receptors is ensured early in
      neutrophil activation. The integrins CR3 and CR4 are located both in secretory
      vesicles and granules, and this diverse subcellular localization may reflect
      their functional versatility. The residence of complement receptors in several
      intracellular compartments ensures a graded upregulation of these receptors in
      response to stimulation.

PMID- 8573285
TI  - Erythrocyte complement receptors.
AB  - Primate erythrocytes express complement receptors (E-CR), which can extrinsically
      bind C3b and Cb4. This interaction allows primate erythrocytes to bind complement
      opsonized particles and immune complexes, a phenomenon historically referred to
      as immune adherence. The binding of C3b and C4b by E-CR also leads to inhibition
      of complement activation. The human E-Cr is the complement activation. The human
      E-CR is the complement receptor type 1, or CR1, which is codominantly expressed
      as four polymorphic allotypes, ranging in size from 190,000 to 280,000 M(r). Non
      human primate E-CR are similar to CR1 in function and antigenicity and are likely
      homologous to CR1 in structure; however, they are one third to one half the size
      of CR1. The physiological role of E-CR, determined from studies in monkeys and
      humans, is to allow erythrocytes to perform as inert shuttles for circulating
      immune complexes (IC), safely directing IC to the organs of the monocyte
      phagocytic system, thus preventing indiscriminate IC deposition in vulnerable
      tissue. In IC-mediated diseases, such as systemic lupus erythematosus (SLE),
      detectable erythrocyte CR1 levels are reduced, an abnormality that in part is
      acquired during disease activity. The loss of erythrocyte CR1 may be an important
      pathogenic factor in the development and severity of SLE.

PMID- 8573286
TI  - The repertoire of T-cell receptors in systemic sclerosis.
AB  - Certain T cell subsets are increased in systemic sclerosis patients, particularly
      V delta 1+ gamma delta T cells in the blood and lungs and CD8+ alpha beta T cells
      in the lungs. The repertoires of T cell antigen receptor (TCR) V delta 1, V
      alpha, and V beta gene families were examined by two methods of analysis. First,
      the relative abundance of V alpha and V beta gene transcripts was determined in
      the blood and bronchoalveolar fluid of the patients. Second, the diversity of the
      junctional regions in TCR V delta 1 transcripts and in different V alpha and V
      beta gene families was analyzed. Limited V delta 1-C delta junctional region
      lengths were observed in the patients compared with controls. This was confirmed
      by sequence analysis of V delta 1-C delta junctional regions after subcloning
      amplified products in a bacterial vector. Evidence for selection of the V delta
      1+ T cells in the tissues of patients came from the findings that the same V
      delta 1-C delta junctional sequences persisted in an individual patient over time
      and that identical junctional sequences were isolated from multiple sites. A
      restricted diversity of the junctional region lengths was also detected in a
      number of V alpha and V beta gene families, particularly within bronchoalveolar
      CD8+ T cell subset. These data suggest that the oligoclonal expansion of the
      corresponding alpha beta and gamma delta T cells is antigen-driven and may be
      important in the pathogenesis of systemic sclerosis.

PMID- 8573287
TI  - Lymphocyte adhesion to endothelium.
AB  - The different homing and recirculation behaviors of lymphocytes depend on
      expression of specific adhesion receptors by lymphocytes and endothelial cells.
      Expression of these receptors is finely regulated according to cell type,
      functional state, and anatomical location, and builds up a complex network of
      interactions that simultaneously involve several of these receptors working as
      "traffic signals" or "postcodes" for lymphocyte migration and homing. There are
      five main families of adhesion molecules: immunoglobulin superfamily, integrins,
      selectins, cadherins, and mucin-like molecules. Together with these "classified"
      receptors, other molecules, such as CD44 and CD38, have been shown to be involved
      in lymphocyte migration and homing. Leukocytes have evolved a intracellular
      system that allows them to maintain these receptors in an inactive state during
      transit in the bloodstream and extracellular-fluids and activate them only when
      proper specific stimuli are delivered. This activity has been called "inside-out"
      signaling. Most receptor/ligand systems regulating lymphocyte migration are not
      selectively dedicated to this function. They are involved in lymphocyte
      interaction with several cell types and play a key role in both the afferent and
      efferent branches of immune responses by mediating lymphocyte interaction with
      APC and target cells. They not only "passively" anchor lymphocytes to these cells
      but also exert an active "outside-in" signaling function that modulates the cell
      response to activation stimuli. In this review, we briefly describe the major
      features of these molecules, survey what is known about their role in
      lymphocyte/endothelium interactions both in vitro and in vivo, and discuss their
      possible therapeutical application.

PMID- 8573288
TI  - Industrial-scale production and rapid purification of an archaeal beta
      glycosidase expressed in Saccharomyces cerevisiae.
AB  - The application of enzymes isolated from extreme thermophiles in biotechnological
      processes is hampered by their unconventional fermentation conditions. The
      expression, in mesophilic hosts, of genes encoding for thermophilic proteins
      enables these difficulties to be overcome and permits the production of enzymes
      in high yield by using conventional fermentation plants and an efficient enzyme
      purification utilizing heat precipitation of host proteins. The beta-glycosidase
      gene from Sulfolobus solfataricus, a thermoacidophilic archaeon growing at 87
      degrees C and pH 3.5, has been cloned and expressed in Saccharomyces cerevisiae
      (baker's yeast). The fermentation of a S. cerevisiae strain on a 100-litre scale
      and the two-step purification of the expressed beta-glycosidase by cell autolysis
      and extracts thermal precipitation is described. This procedure, after 72 h of
      autolysis, gave a yield 56-fold higher with respect to that obtained with the
      beta-glycosidase from S. solfataricus.

PMID- 8573289
TI  - Production of bovine-pancreatic-trypsin-inhibitor homologues in Escherichia coli
      and their characterization.
AB  - Biologically active bovine pancreatic trypsin inhibitor (BPTI) was produced in
      Escherichia coli using an OmpA leader-peptide fusion-protein system, and BPTI
      homologues were generated by cassette mutagenesis. Amino acids in the reactive
      loop of alpha 1-proteinase inhibitor (alpha 1-PI) were incorporated into the
      reactive loop of BPTI in a stepwise approach such that the contribution of
      individual amino acids could be assessed. The introduction of mutations into BPTI
      diminished the yield of heterologous protein relative to wild-type BPTI. However,
      for three BPTI homologues sufficient material was isolated to allow
      characterization of the proteins by electrospray MS and N-terminal peptide
      sequencing.

PMID- 8573290
TI  - Lactate catabolism by enzyme-loaded red blood cells.
AB  - Two different enzymes that metabolize lactate in the presence of oxygen, either
      to acetate plus CO2 (lactate 2-mono-oxygenase; Lmox) or to pyruvate plus H2O2
      (lactate oxidase; Lox) were encapsulated in human and murine red blood cells
      (RBCs). Lmox shows a low affinity for lactate (Km 22 mM) and thus works at a low
      rate at the lactate concentrations found in hyperlactataemia (5-20 mM).
      Encapsulation of Lox provides a constant catabolic rate under the same range of
      blood lactate concentrations, but generates H2O2, which is toxic to the enzyme
      loaded RBCs. Co-encapsulation of both enzymes at a ratio of 20 units of Lmox/unit
      of Lox results in significant rates of lactate metabolism over a wide range (1-30
      mM) of lactate concentrations with modest methaemoglobin formation (5-8.5%) and
      normal cellular ATP concentrations (1.1-1.23 mM). In vitro experiments with [1
      14C]glucose and [U-14C]glucose have shown that Lmox/Lox-loaded RBCs counteract
      the production of H2O2 by increasing the amount of glucose metabolized in the
      pentose phosphate pathway. In vivo attempts to prove the efficacy of these
      engineered RBCs in removal of blood lactate in mice have failed because of the
      high aerobic capacity and high lactate metabolism of these animals. However, the
      results obtained in vitro suggest that the encapsulation of lactate-catabolizing
      enzymes may be useful in the treatment of hyperlactataemia.

PMID- 8573291
TI  - Binding of beta 2 glycoprotein I to activated polystyrene and its recognition by
      human IgG autoantibodies.
AB  - Beta 2 glycoprotein I (apolipoprotein H, beta 2GPI) is involved in the formation
      of epitope(s) recognized by clinically relevant autoantibodies from patients with
      antiphospholipid syndrome. We studied the binding of beta 2GPI to chemically
      activated polystyrene in a microtitre plate format. Adsorption isotherms (at 37
      degrees C) were generated for beta 2GPI on activated polystyrene and on
      unactivated polystyrene, with both human serum antibodies and rabbit polyclonal
      IgG antibodies as probes, and horseradish peroxidase (HRP)-tagged anti-IgG to
      detect binding. Additionally, beta 2GPI was biotinylated and isotherms were
      developed by using HRP-streptavidin as the recognition sequence. Human serum
      autoantibodies, which did not precipitate beta 2GPI in solution, yielded a
      characteristic chemisorption isotherm on activated polystyrene but did not
      recognize beta 2GPI bound to untreated polystyrene. The rabbit IgG, which did
      precipitate beta 2GPI in solution, detected beta 2GPI bound to both activated
      polystyrene and, to a lesser extent, to untreated polystyrene. The binding of
      beta 2GPI to untreated polystyrene was confirmed by the use of biotinylated beta
      2GPI. To assess the prevalence of IgG anti-beta 2GPI autoantibodies, we surveyed
      113 sera submitted to our laboratory for anticardiolipin antibody (aCL) testing.
      Only nine (8%) had anti-beta 2GPI activity greater than two standard deviations
      above the mean for those sera in which aCL activity was within normal limits. We
      conclude that epitope presentation of beta 2GPI for human autoantibody binding is
      dependent on surface properties of the polystyrene, and that beta 2GPI
      autoantibodies are found only in a subpopulation of sera positive for aCL.

PMID- 8573292
TI  - Purification and characterization of copper-metallothionein from Aspergillus
      niger by affinity chromatography.
AB  - Biomass of Aspergillus niger was obtained from a microbial culture and a copper
      (Cu) induction was performed after 72 h of fermentation. The crude induced
      metallothionein extract was obtained by cell disruption and partly purified by a
      heat treatment and ultrafiltration. The purification of metallothionein by
      affinity chromatography resulted in three major fractions: FIVa, FIVb and FIVc3.
      Cu analysis demonstrated that only fraction FIVc contained the Cu
      metallothionein. Spectrophotometric analyses of FIVc demonstrated the presence of
      a peak at 259 nm and a ratio of 78 mol of Cu per mol of protein. Electrophoretic
      analyses of FIVc, performed under denaturing conditions, showed the presence of
      one band with molecular mass of 21 kDa; however, two isoforms were observed under
      native conditions with molecular masses of 9.5 and 10.5 kDa and isoelectric
      points of 6.2 and 6.5, suggesting a recombination process due to denaturation.

PMID- 8573293
TI  - Stable-isotope studies of glutamate catabolism in Fusobacterium nucleatum.
AB  - Catabolism of glutamate was investigated in Fusobacterium nucleatum, an anaerobic
      micro-organism that is strongly implicated in periodontal disease. The
      distribution of labels in acetate and butyrate derived from [13C]glutamates was
      determined by NMR spectroscopy and MS. The label from L-[5-13C]glutamate was not
      incorporated, whereas C-1 of acetate and butyrate were efficiently labelled by L
      [1-13C]glutamate; these results indicated that the hydroxyglutarate pathway
      predominated. In butyrate, enrichment at C-3 was smaller than C-1; that this was
      not due to participation of the methylaspartate pathway was demonstrated by the
      incorporation of label from L-[4-13C]glutamate into only C-2 of acetate and C-4
      (major)/C-2 (minor) of butyrate. The presence of label at a second site in
      butyrate was attributed to the synthesis of butyrate from acetate and verified by
      the incorporation of label from [1,2-13C2]- and [2H3]-acetate.

PMID- 8573294
TI  - Lipid formulations of amphotericin B. Less toxicity but at what economic cost?

PMID- 8573295
TI  - Management of adverse effects of disease-modifying antirheumatic drugs.
AB  - Therapy with disease modifying antirheumatic agents (DMARDs) is often complicated
      by the occurrence of adverse effects. Although risk factors for several DMARDs
      have been reported, the prediction of adverse drug reactions is not yet possible.
      Therefore regular monitoring remains mandatory. Monitoring for adverse effects to
      DMARDs usually includes one or more of the following: blood count, liver, kidney,
      urine or ophthalmologic tests. Since most adverse reactions occur during the
      first few months of treatment, monitoring should be more intense and frequent in
      this initial phase. Some adverse effects are dose-dependent, and therefore dosage
      reduction may help alleviate these. Others are idiosyncratic, and often
      necessitate drug withdrawal. Except for (hydroxy)chloroquine-induced retinopathy
      and methotrexate-induced liver cirrhosis, most adverse reactions to DMARDs are
      fortunately reversible.

PMID- 8573297
TI  - Risks and benefits of retinoids in the chemoprevention of cancer.
AB  - Chemoprevention of cancer is a new branch of clinical research; it may be defined
      as the reduction of cancer incidence by pharmacological means through the
      suppression of established malignant cell clones or through alteration in growth
      and progression of premalignant cell populations. In the last few years, this
      area of research has progressed dramatically from preclinical studies to phase I,
      II and III clinical trials. Among the various chemical or natural compounds used
      as chemopreventive agents, retinoids appear to be one of the most promising
      groups of agents. Analyses of preclinical and clinical studies have shown
      retinoids to be active in reversing skin and oral precancer, in preventing
      primary skin cancer, superficial bladder cancer, and second primary tumours
      associated with head and neck and lung cancers. Preclinical studies have shown
      evidence of the activity of fenretinide in breast cancer. Preliminary clinical
      data seem to show a protective effect of fenretinide against ovarian cancer.
      Current evidence therefore suggests that chemoprevention of cancer with retinoids
      is a promising path.

PMID- 8573296
TI  - Comparative adverse effect profiles of platinum drugs.
AB  - Since the discovery of the biologically active platinum complexes 30 years ago, 2
      agents have become widely established in clinical oncology practice. Both
      cisplatin and carboplatin are platinum(II) complexes with 2 ammonia groups in the
      cis- position. However, they differ in their solubility, chemical reactivity,
      dichloride or alicyclic oxygenated leaving groups, pharmacokinetics and
      toxicology. Cisplatin causes severe renal tubular damage and reduces glomerular
      filtration, and requires concurrent saline hydration and mannitol diuresis to
      eliminate potentially lethal and unacceptable damage to the kidneys. Carboplatin,
      at conventional doses, causes no decrease in glomerular filtration and only minor
      transient elevations in urinary enzymes. Cisplatin is the most emetic cancer drug
      in common use, while nausea and vomiting associated with carboplatin are
      moderately severe. Serotonin release from enterochromaffin gut mucosal cells and
      stimulation of serotonin 5-HT3-receptors mediates acute emesis. Selective
      inhibitors of the 5-HT3-receptor protect against cisplatin- and carboplatin
      induced nausea and vomiting. Peripheral neurotoxicity is the most dose-limiting
      problem associated with cisplatin. Loss of vibration sense, paraesthesia and
      sensory ataxia comes on after several treatment cycles. Carboplatin, however, is
      relatively free from peripheral neurotoxicity. Audiometry shows cisplatin-induced
      ototoxicity in 75 to 100% of patients, which may be associated with tinnitus and
      hearing loss. Ototoxicity is rare with conventional dose carboplatin therapy.
      Monitoring hearing with audiograms may identify early signs before significant
      impairment occurs. Cisplatin causes mild haematological toxicity to all 3 blood
      lineages. Haematological toxicity is dose-limiting for carboplatin, with
      thrombocytopenia being a greater problem than leucopenia. Although carboplatin is
      not toxic to the kidney, renal function markedly affects the severity of
      carboplatin-induced thrombocytopenia. The major clearance mechanism of cisplatin
      is irreversible binding in plasma and tissues, while carboplatin is cleared by
      glomerular filtration. Metabolism of cisplatin to aqua, amino acid and protein
      species is extensive, whereas carboplatin exists mainly as the free unchanged
      form. Strong relationships between carboplatin renal clearance, glomerular
      filtration rate, area under the plasma concentration-time curve (AUC) of
      filterable platinum and severity of thrombocytopenia have prompted dose
      adjustment according to renal function. New analogues such as JM216 offer the
      potential advantages of oral administration and few nonhaematological toxicities.
      Analogues based on the diaminocyclohexane ligand have encountered problematic
      neurotoxicity.

PMID- 8573299
TI  - Halofantrine in the treatment of malaria.

PMID- 8573300
TI  - Malaria vaccines.

PMID- 8573302
TI  - Transplantation.

PMID- 8573301
TI  - Malaria vaccine trials: SPf66 and all that.

PMID- 8573298
TI  - An assessment of short-acting hypnotics.
AB  - Insomnia, the experience of poor quality or quantity of sleep, is a very common
      complaint. Approximately 65 million adults (36% of the American population)
      complain of poor sleep, and of this group, 25% have insomnia on a chronic basis.
      These chronic insomniacs not only report higher rates of difficulty with
      concentration, memory and the ability to cope with minor irritations but also
      have 2.5 times more fatigue-related automobile accidents than do good sleepers.
      Despite its ubiquity, insomnia is often either untreated or inadequately treated.
      Short-acting hypnotics are advocated for transient insomnia, which lasts less
      than 3 weeks, and in patients with chronic insomnia as an adjunctive treatment
      where nonpharmacological treatment is not sufficient to alleviate insomnia and
      the related daytime detrimental effects. The putative adverse effects of
      hypnotics must be weighted against the severe health effects caused by continued
      sleep impairment. If hypnotic agents are used, they should be taken nightly only
      for brief use, or intermittently in longer term use. Benzodiazepines, zolpidem
      and zopiclone (in countries where the latter is available) remain the recommended
      hypnotic agents, although in the past few years there has been much criticism in
      lay magazines and on television about the use of benzodiazepines. However, this
      review of the efficacy and tolerability data of the short-acting hypnotics
      suggests that triazolam is comparable with other short-acting hypnotics at
      equipotent doses while taking into consideration that for every hypnotic,
      different study populations display different degrees of efficacy. In addition,
      contrary to previous suggestions that such adverse effects are rebound insomnia
      and anterograde amnesia are unique to triazolam, hypnotically equivalent doses of
      tirazolam have not been shown to produce these effects more frequently than other
      short-acting hypnotics. The newer nonbenzodiazepine hypnotics seem to be equally
      efficacious as the short-acting benzodiazepines; whether they will truly have a
      better adverse effect profile will be determined as more clinical experience
      accumulates. Despite the availability, relative safety and efficacy of these
      newer hypnotic agents, they should not be perceived as the sole treatment for
      insomnia and should be used in conjunction with nonpharmacological techniques
      (such as adherence to good sleep hygiene, sleep restriction, stimulus control and
      biofeedback therapy).

PMID- 8573303
TI  - CD28 and apoptosis.
AB  - Until recently, it was thought that signal transduction through CD28 and the
      related molecule CTLA4 prevented the induction of anergy in T cells activated
      through the TCR. This hypothesis has been suggested as an explanation for how
      soluble forms of CTLA4, which bind the CD28/CTLA4 ligands B7-1 and B7-2, can
      prevent graft rejection. Recent reports suggest that another function of CD28
      costimulation is the regulation of T-cell survival. CD28 not only enhances IL-2
      production, which can act as an extrinsic regulator of cell survival, but also
      augments the expression of the intrinsic survival factor Bcl-xL. In contrast,
      CTLA4-mediated signal transduction has been reported to induce cell death in
      previously activated T cells. These data suggest that B7-1/B7-2 signaling not
      only controls cell proliferation and T-helper cell subset selection, but also T
      cell survival.

PMID- 8573304
TI  - The role of natural killer cells in transplantation.
AB  - Natural killer cells express receptors for polymorphic MHC class I molecules that
      inhibit cytotoxicity mediated by natural killer cells. The genes encoding the
      mouse and human natural killer cell receptors for MHC class I have recently been
      cloned, and there is rapid progress in elucidating their structure and function.
      These receptors may be important in bone marrow transplantation and explain the
      phenomenon of hybrid resistance.

PMID- 8573305
TI  - Cytokines and transplantation: Th1/Th2 regulation of the immune response to solid
      organ transplants in the adult.
AB  - It has been very tempting to accept the suggestion that the route to rejection or
      tolerance of organ transplants is determined by T-helper type 1 and type 2 cells,
      respectively. Much of the data used to support this idea, however, is indirect
      and therefore cannot be used to imply a causal role for either population as
      suggested. Recent experiments have been aimed at further expanding knowledge in
      this area and conclude that the expansion of neither population alone inevitably
      results in graft damage or tolerance.

PMID- 8573306
TI  - IL-10 immunosuppression in transplantation.
AB  - The description of IL-10 as an immunosuppressive cytokine that inhibits numerous
      T-cell and antigen-presenting cell functions has led to the investigation of the
      role of IL-10 in graft acceptance and rejection, in both manipulated and
      unmanipulated experimental systems. Recent results suggest a complex interaction
      of IL-10 with other cytokines and numerous cell types. Although IL-10 is not a
      simple immunosuppressive molecule, manipulation of its actions may be a useful
      approach for prolonging graft survival and preventing rejection.

PMID- 8573307
TI  - Immunosuppressive peptides corresponding to MHC class I sequences.
AB  - The induction of tolerance is a long-standing goal in transplantation. Intact MHC
      molecules, or fragments of them, are being used to render T cells unresponsive
      both in vitro and in vivo. Elucidation of the mechanisms underlying the effects
      of these treatments should aid the design of novel therapies for transplantation.

PMID- 8573308
TI  - Predicting graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD) is a serious complication that occurs after
      allogeneic bone marrow transplantation and contributes to transplant-related
      morbidity and mortality. Recent advances in the measurement of recipient-specific
      alloreactivity before marrow grafting have led to the development of in vitro
      assays that sufficiently predict the occurrence of moderate to severe acute GVHD.
      This predictive information provides the basis for attempts to minimize, or
      prevent, GVHD by prospective donor selection and individualized immunotherapeutic
      strategies.

PMID- 8573309
TI  - The role of chromosome translocations in T cell acute leukemia.
AB  - A variety of unique chromosome translocations are found in the malignant cells of
      patients with T cell acute lymphoblastic leukemia (T-ALL). Molecular analysis of
      these translocations has implicated nine different proto-oncogenes in the
      pathogenesis of T-ALL. Despite the apparent genetic complexity of this disease,
      recent studies have uncovered a common pathway of T-ALL development that involves
      two distinct families of transcription factors.

PMID- 8573310
TI  - New models of lymphoma in transgenic mice.
AB  - We are in a 'golden age' of mouse genetics. Genetic engineering and
      micromanipulation techniques now allow not only the overexpression or
      misexpression of transgenes randomly inserted into the mouse genome, but also the
      directed homologous replacement of normal genes with transgenes coding for null
      or mutant alleles (gene 'knockouts'). Both of these approaches have been used in
      the past 1-2 years to illuminate the contributions of novel oncogenes and of anti
      oncogenes to the molecular basis of lymphomagenesis.

PMID- 8573311
TI  - New tumor antigens recognized by T cells.
AB  - A series of tumor cell antigens that are recognized by cytolytic T lymphocytes
      has been characterized this year. Besides the antigens derived from proteins
      specifically expressed in tumors, many melanoma antigens derive from melanocytic
      differentiation proteins. In addition, antigens unique to individual tumors
      result from mutations in ubiquitously expressed genes.

PMID- 8573312
TI  - Manipulation of costimulatory signals to enhance antitumor T-cell responses.
AB  - One of the major goals of tumor immunotherapy is the induction of tumor-specific
      T-cell responses that will be effective in eradicating disseminated tumors.
      Emerging information on the role of costimulatory molecules in T-cell activation
      offers several new strategies for enhancing antitumor responses, including the
      induction of expression of costimulatory molecules on tumor cells, enhancement of
      the presentation of transferred tumor antigen by host antigen-presenting cells,
      and ex vivo antigen priming of autologous antigen-presenting cells.

PMID- 8573313
TI  - Hematopoietic stem cell transplantation for cancer therapy.
AB  - Bone marrow transplantation has become well established in the treatment of
      malignant disorders. High-dose chemotherapy with hematopoietic stem cell support
      is widely used for most hematological malignancies, as well as for some solid
      tumors. In the light of recent developments in blood progenitor cell harvest,
      there have been clinical trials with autologous and allogeneic transplants. In
      particular, the availability of large numbers of blood stem cells, mobilized by
      granulocyte colony-stimulating factor and collected by leukapheresis, has made it
      possible to overcome histocompatibility barriers in HLA-mismatched leukemia
      patients. Other recent developments include new methods for blood progenitor
      cells mobilization and ex vivo expansion, the use of umbilical cord blood as an
      alternative source of stem cells, and molecular techniques that may, in the
      future, provide other modalities of purging tumor cells from autologous grafts.

PMID- 8573314
TI  - The killer and the executioner: how apoptosis controls malignancy.
AB  - An escalating research effort focused on apoptotic cell death continues to chip
      away at the central mechanisms of this intriguing process. One of the areas in
      which this research has already yielded fundamental insights is in the analysis
      of oncogenesis, where defects in cell death can have profound effects. Recent
      progress has been made in understanding the processes of apoptosis induction,
      transduction, and effect (or 'execution'), especially with respect to our
      understanding of malignancy, hyperplasia and related phenomena.

PMID- 8573316
TI  - Transplantation.

PMID- 8573315
TI  - The role of natural killer cells in immune surveillance of cancer.
AB  - In the past year, a subset of natural killer cells designated 'A-NK cells' has
      been characterized. These immune cells appear to be able to enter solid tissues,
      migrate to sites of metastasis and eliminate malignant tissue cells, but spare
      normal tissue cells. They appear to be ideal surveillance cells, readily capable
      of upregulating antitumor functions in response to local activation signals.

PMID- 8573317
TI  - Cancer.

PMID- 8573318
TI  - Instability of the mutated biotin operon plasmid in a biotin-producing mutant of
      Serratia marcescens.
AB  - The growth of a d-biotin-producing strain of Serratia marcescens (SB412) was
      strongly inhibited by the introduction of pLGM412, a low-copy-number plasmid
      containing the complete biotin (bio) operon derived from SB412, whereas the wild
      type strain was not inhibited by the plasmid. SB412 carrying pLGM412 was
      genetically unstable; large colonies appeared spontaneously from the background
      small colonies. When the plasmids from the large colonies were transformed into
      the SB412 host, all of the resultant transformants showed a large-colony
      phenotype, suggesting that the large-colony phenotype is due to mutations in the
      plasmid-born bio genes. Some of these plasmids were structurally altered and the
      others were not. Furthermore, the structurally altered plasmids were classified
      into a deleted and an elongated type. All of the mutated pLGM412 derivatives
      reduced or lacked the bio gene expression, indicating that the high expression of
      bio gene(s) causes the growth inhibition. By subcloning experiments, biotin
      synthase (the bioB gene product) was responsible for the growth inhibition.

PMID- 8573319
TI  - Adaptive predictive control of dissolved oxygen concentration in a laboratory
      scale bioreactor.
AB  - We present an algorithm for the adaptive control of dissolved oxygen
      concentration in a bioreactor, based on the agitation rate. The dynamics are
      represented by an incremental first-order model with variable dead-time and
      parameters. These are estimated on-line by a recursive least-squares
      identification method with a forgetting factor and a constant sensitivity. The
      model is employed to predict the behaviour of the dissolved oxygen concentration
      over a finite horizon, using an original method which requires little
      computation. Then, a Generalized Predictive Control optimisation strategy
      computes the agitation rate from the predictions and the desired set point, while
      gradually updating the controller smoothness. This algorithm, which requires
      little preliminary knowledge, has been implemented on a laboratory-scale fed
      batch bioreactor for which the use of conventional controllers showed limited
      performance, due to the unpredictable and evolutive nature of the dynamics. The
      new controller proved to be robust and effective over a wide range of operating
      conditions, while requiring no operator adjustments.

PMID- 8573320
TI  - Effects of the hydrodynamic environment and shear protectants on survival of
      erythrocytes in suspension.
AB  - Survival of media-suspended porcine erythrocytes exposed to various hydrodynamic
      environments was investigated with and without such shear protectant additives as
      bovine serum albumin, dextran and the non-ionic surfactant Pluronic F68.
      Erythrocytes provided a model cell population with cells of a uniform size,
      metabolic state and shear tolerance. Because the cells were non-growing, any
      shear adaptation effects were avoided. Cell lysis was followed by microscopic
      counts or release of haemoglobin. The cells were susceptible to agitation damage
      in unaerated shake flasks agitated at 100 rpm or greater. Relative to additives
      free operation, the presence of 0.1% (w/v) dextran or albumin prolonged cell
      survival, but Pluronic F68 actually enhanced cell lysis in flasks agitated at 100
      rpm. The protective effect of the additives depended on the hydrodynamic
      conditions. The protective effect of albumin was demonstrated also in aerated
      conditions in a split-cylinder airlift bioreactor (aspect ratio of 8.8; riser-to
      downcomer cross-sectional area ratio of 1.0; specific power input of 0.34 W m-3).
      Comparison of the cell lysis characteristics in the airlift device and the best
      case performance of the shake flask showed longer survival in the flask (100
      rpm); however, the length of survival in the reactor (approx. 70 h) was
      sufficient for practical purposes. In all cases, the cell lysis pattern conformed
      initially to zero-order dependence in cell concentration, becoming first-order
      after varying degrees of exposure to hydrodynamic forces. Fatigue failure of
      cells was inferred.

PMID- 8573321
TI  - Effect of PQQ glucose dehydrogenase overexpression in Escherichia coli on sugar
      dependent respiration.
AB  - Pyrroloquinoline quinone glucose dehydrogenase (PQQGDH) was overexpressed in
      Escherichia coli, and its impact on sugar-dependent respiration was investigated.
      Sugar-dependent respiration patterns under PQQGDH overexpression can be devided
      into two types. The first type involves D-glucose and D-mannose, which are
      utilized by the phosphotransferase system (PTS) and are also the substrates of
      PQQGDH. As a result of PQQGDH overexpression, the apparent Km value of sugar
      dependent respiration shifted to higher concentration compared with E. coli
      parental cells. The second type included D-xylose and D-galactose, which are the
      substrates of PQQGDH, but not the PTS sugars. PQQGDH overexpressing cells showed
      much higher respiration than parental cells. These results suggested that PQQGDH
      overexpression may alter sugar utilization preferences in E. coli, suggesting
      further possible applications in metabolic engineering for carbon source
      utilization.

PMID- 8573322
TI  - Studies on plasmid stability and LTB production by recombinant Vibrio cholerae in
      batch and chemostat cultures: a lesson for optimizing conditions for chemical
      induction.
AB  - Plasmid content, its stability and the expression of B-subunit of Escherichia
      coli heat-labile enterotoxin (LTB) in Vibrio cholerae/r-pMMB68 system have been
      studied in batch as well as in chemostat cultures. Upon induction with isopropyl
      beta-D-thiogalactopyranoside (IPTG), cultures secreted LTB into the extracellular
      milieu. Highest specific LTB production rate of 7.3 mg mg-1h-1 was achieved in
      batch culture induced at the late exponential growth phase. The plasmid pMMB68
      was fairly stable up to 20 generations, even in the absence of selection
      pressure. Instability of the plasmid was accelerated in the presence of IPTG and
      at higher dilution rates. Maximum productivity of 2.1 mg l-1 h-1 was achieved in
      continuous culture, which remained constant at a range of dilution rates from
      0.20 to 0.35 h-1.

PMID- 8573323
TI  - Bioluminescent detection of RNA with sequence-specificity using RNA binding
      protein-luciferase fusion protein.
AB  - A novel bifunctional reagent has been synthesized for RNA detection by genetic
      fusion of a sequence-specific RNA binding protein and firefly luciferase. The RNA
      binding protein used in this study recognizes the oligoribonucleotide rH4 which
      contains four (UUAGGG)-repeat sequence, while luciferase works as a
      bioluminescent marker. The constructed fusion protein exhibited both sequence
      specific RNA binding and bioluminescent activities. The rH4 and rECGF, which has
      an unrelated sequence having the same length as rH4, were immobilized on a nylon
      membrane. The membrane was pre-treated by 5% bovine serum albumin and soaked into
      a fusion protein solution. Bioluminescent detection has successfully been
      performed at more than 50 pmol of rH4, so the detection limit using this protein
      was 50 pmol. However, no appreciable bioluminescence was induced by rECGF.

PMID- 8573324
TI  - Erythropoietin--improving the quality of life of dialysis patients.

PMID- 8573325
TI  - Interferon beta-1b for the treatment of multiple sclerosis.

PMID- 8573326
TI  - Timing and competition in networks representing ambiguous figures.
AB  - The duration of perception for eye rivalry and the Necker cube was obtained
      during continuous presentation of the stimuli. The frequency histograms support
      the idea of continuous competition between the neural representations of both
      percepts. They also suggest that when a percept is installed there is a relative
      refractoriness for changing the percept that is modeled by a sigmoid equation.
      This refractoriness lasts a few seconds. The duration of the perceptions was
      modified by the instruction to the subjects. Results are discussed in terms of a
      simple competition model, a temporal segmentation hypothesis, and the possible
      top-down influences. These are considered useful mechanisms for selecting
      relevant information in a serial processor and for maintaining perception,
      cognitive evaluation, and action of a given context in the same time epoch.

PMID- 8573327
TI  - Shifting behavior: an analysis of response patterns of Parkinson patients in
      discrimination learning.
AB  - Parkinson patients often show decreased performance on what is generally referred
      to as "shift tasks." This does not necessarily imply that Parkinson patients have
      problems with shifting, since task performance reflects not only shifting but
      also other factors. Using a discrimination learning task, we analyzed response
      patterns to determine the decision rules used. As well, we varied the manner of
      problem alternation (implicit versus explicit) and the type of problem
      alternation (extradimensional versus intradimensional shifts). In accordance with
      the literature, we found that Parkinson patients needed more trials to solve the
      problems. However, the response patterns of the Parkinson patients and controls
      were practically the same. An important finding was that Parkinson patients did
      not hold on longer to a rule, which was correct in a former problem, than
      controls did. Therefore, we concluded that Parkinson patients are able to shift
      from one decision rule to another.

PMID- 8573328
TI  - Medial olivocochlear system and loudness adaptation: differences between
      musicians and non-musicians.
AB  - Simple loudness adaptation and crossed olivocochlear feedback were investigated-
      through the Tone Decay Test (TDT) and Transiently Evoked Otoacoustic Emission
      (TEOAE) recording, respectively--in a sample of normal-hearing subjects including
      both musicians and non-musicians. The results for musicians and non-musicians
      differed statistically: the musicians showed on average less loudness adaptation
      and a greater reduction in TEOAE amplitude under contralateral acoustic
      stimulation, suggesting a stronger medial efferent feedback on the auditory
      periphery in these subjects. This finding, that not only psychoacoustic
      performance but also the physiological mechanism is different in musicians,
      strongly suggests that the latter should, like the former, be influenced by
      auditory "training" such as music studies. This perspective is discussed in
      detail in the text, since it raises puzzling questions and outlined promising
      issues in the field of auditory psychophysiology.

PMID- 8573329
TI  - Reading direction and attention: effects on lateralized ignoring.
AB  - The effects of the scan for the first element in reading (leftmost in English,
      rightmost in Hebrew) on the ability of subjects to ignore irrelevant stimuli in
      one visual field more than in the other were investigated. The hypothesis tested
      was that English readers would have a harder time ignoring irrelevant stimuli in
      the left visual field than in the right visual field, with the opposite pattern
      predicted for readers of Hebrew. The paradigm employed by Banich (Banich &
      Belger, 1990) was used with two letter matching tasks. The results showed that
      when an irrelevant letter was present, English readers responded more slowly in
      the right than in the left visual field, and Hebrew readers showed the opposite
      pattern (Experiment 1). This interaction did not occur when the irrelevant letter
      was deleted (Experiment 2). These findings are discussed in terms of their
      relation to eye movements and covert attention and to the use of bilateral
      displays in neuropsychological experiments.

PMID- 8573330
TI  - Lexicalization errors in writing arabic numerals: a single-case study.
AB  - This paper presents a single-case study of a patient suffering from several
      impairments in number processing. The main focus of the paper is to describe and
      interpret the patient's errors in verbal to arabic transcoding. The errors were
      of the syntactical type and consisted of partial lexicalizations appearing mainly
      in response to items with Thousand in sum relationships and less frequently with
      Hundred in sum relationships. The Discussion section compares three models in
      their ability to account for the patient's dissociation. It was suggested that
      models such as that of McCloskey, Caramazza, and Basili (1985), postulating a
      semantic representation for numbers built up on a base-ten system, are unable to
      account for the patient's errors. By contrast, Power et al.'s perspective (Power
      & Longuet-Higgins, 1978; Power & Dal Martello, 1990), which posits a semantic
      representation of numbers reflecting the structure of the verbal numeral system,
      could provide an economical interpretation for the dissociation observed between
      the mastery of sum and product relationships. Similarly, the asemantic
      transcoding model developed by Deloche and Seron (1987) gives a valid account for
      the patient's profile.

PMID- 8573331
TI  - Changes in cognitive asymmetries from waking to REM and NREM sleep.
AB  - In previous studies, a right hemisphere superiority was shown during REM sleep
      with respect to Wake and NREM states for right hemisphere tasks. The question can
      be raised whether the increasing right hemisphere performance during REM is
      related to right hemisphere tasks only, or whether it is of more general nature.
      This hypothesis was tested by giving the lateralized Consonant Recognition Task
      to 16 subjects during waking and upon awakenings from REM and NREM sleep. Results
      support the hypothesis that right hemisphere superiority in REM sleep is not
      restricted to right hemisphere tasks.

PMID- 8573332
TI  - Altered visual field asymmetries for letter naming and letter matching as a
      result of concurrent presentation of threatening and nonthreatening words.
AB  - Thirty-two right-handed subjects (16 male and 16 female students) were
      administered a unilateral letter-naming task and two unilateral letter-matching
      tasks: physical-identity letter matching (shape task) and nominal-identity letter
      matching (name task). Each task contained three conditions. In control
      conditions, no concurrent task was given. In threat and nonthreat conditions,
      each unilateral stimulus was preceded by a centrally presented threatening or
      nonthreatening word. Subjects were instructed to recall this word after their
      response to the lateral stimulus. With letter naming, each trial consisted of
      three consonants presented horizontally to the left or right visual field. Across
      conditions, subjects identified more letters correctly in the right visual field
      than in the left visual field. The concurrent presentation of threatening words
      resulted in a selective enhancement of left visual-field performance. In the
      control condition of the shape task, same letter pairs were identified faster
      than different pairs when they were presented to the right visual field. The
      concurrent presentation of threatening words resulted in a selective shortening
      of left visual-field latencies to same pairs. In the name task, the concurrent
      presentation of threatening words resulted in improved accuracy on left visual
      field trials. No sex differences in perceptual asymmetries and in emotional
      priming effects were found. The results demonstrate that threatening stimuli can
      activate the right hemisphere and alter the laterality patterns for several
      tasks.

PMID- 8573333
TI  - Gesture laterality in aphasic and apraxic stroke patients.
AB  - Limb preference during conversational gestures may be a reflection of functional
      hemispheric asymmetries. In right-handers, speech and praxis are usually mediated
      by the left hemisphere and in conversation, right-handers gesture more with their
      right than left hand. However, patients with left hemisphere brain damage, who
      are aphasic and apraxic but not hemiplegic, may use their right hemisphere to
      compensate for their left. Therefore, we investigated spontaneous lateralized
      gesture production during conversation in a group of left hemisphere-damaged
      stroke patients, who were aphasic and apraxic but not hemiparetic, and compared
      their performance to a group of matched controls. Whereas the control group had a
      strong right-hand preference, the nonparetic but apraxic and aphasic stroke
      patients were as likely to produce gestures with the right, left, or both hands.

PMID- 8573334
TI  - Cell-to-cell contact and extracellular matrix.
AB  - The topics discussed in this overview only scratch the surface of the contents of
      this issue, and necessarily reflect only some of the highlights that can be
      gleaned from the articles. The reader will learn a great deal more from this
      issue, which contains a particularly rich selection of very current topics, in
      both the traditional and new areas in the field. There continues to be remarkable
      progress towards understanding the mechanisms by which the different systems of
      cell-cell and cell-matrix contacts establish and regulate physical adhesive
      interactions and mediate transmembrane signaling processes in various tissues.

PMID- 8573335
TI  - Morphogenetic roles of classic cadherins.
AB  - Classic cadherins, which are known to be crucial for homotypic cell-cell
      adhesion, have been found to be present not only in vertebrate but also in
      invertebrate species. Their three-dimensional structures, novel functions, and
      novel expression patterns were reported recently. These have been important steps
      towards a deeper understanding of the morphogenetic roles of this family of
      molecules.

PMID- 8573336
TI  - Cell adhesion molecules as morphoregulators.
AB  - Many significant advances have been made recently in our understanding of the
      structure and function of cell adhesion molecules (CAMs). The most provocative,
      however, are those that indicate that CAM-mediated adhesion may lead to changes
      in gene expression and those that suggest that the expression of CAM genes may be
      regulated by the products of Hox and related genes.

PMID- 8573337
TI  - Signal transduction of beta-catenin.
AB  - Beta-catenin participates in signal transduction and developmental patterning in
      Xenopus and Drosophila embryos as a component of the Wnt signaling pathway. Its
      signaling activity is distinct from its role in cadherin-mediated cell adhesion,
      and it probably acts either in the cytosol or in the nucleus. The adenomatous
      polyposis coli tumor suppressor protein is also implicated in beta-catenin
      signaling.

PMID- 8573338
TI  - Tight junctions, membrane-associated guanylate kinases and cell signaling.
AB  - Proteins that define a new family, termed membrane-associated guanylate kinases,
      have recently been identified as structural components of epithelial tight
      junctions and neuronal synapses, and as cell signaling proteins in Drosophila and
      Caenorhabditis elegans. In particular, the lin-2 gene has been shown to encode a
      membrane-associated guanylate kinase and to act in the let-23 receptor tyrosine
      kinase/let-60 ras signaling pathway that controls vulval induction in C. elegans.
      The combined data from recent biochemical and genetic analyses of membrane
      associated guanylate kinases suggest that certain tight junction proteins can
      play an important role in cell signaling pathways. One possibility is that
      asymmetric segregation of signaling receptors to the basolateral membrane domain
      of polarized epithelial cells is crucial for proper cell signaling, and that
      membrane-associated guanylate kinases may be required for this localization.

PMID- 8573339
TI  - Protein tyrosine phosphatases as adhesion receptors.
AB  - The intracellular segments of classic adhesion molecules such as N-CAM do not
      show structural similarity to any known signaling molecules. This suggests that
      their effects on signaling responses must be exerted indirectly through
      associated proteins. In contrast, many receptor protein tyrosine phosphatases
      (RPTPs) possess extracellular segments with homology to cell adhesion molecules
      linked directly to intracellular segments comprising one or two protein tyrosine
      phosphatase catalytic domains. Therefore, the RPTPs have the potential for direct
      modulation of catalytic function through engagement of the extracellular segment,
      suggesting they could be direct signal transducers of cell contact phenomena. In
      the past few years, some RPTPs have been shown to effect cell-cell adhesion
      directly via homophilic binding or indirectly by association with known cell
      adhesion molecules. In addition, RPTPs have been localized to points of cell-cell
      or cell-matrix contact, indicating their potential to regulate these structures.

PMID- 8573340
TI  - Towards molecular mechanisms for gamete adhesion and fusion during mammalian
      fertilization.
AB  - The process of fertilization is fundamental to the maintenance of life. The
      ability of unfertilized eggs and free-swimming sperm to recognize, adhere to, and
      fuse with each other are vital aspects of the fertilization process. Significant
      progress has been made recently in identifying and characterizing (glyco)proteins
      that are associated with the surface of mammalian gametes and that support
      adhesion and fusion of eggs and sperm. As a result, there are currently reasons
      to believe that, in mammals, species-specific gamete adhesion is carbohydrate
      mediated and gamete fusion is intergrin-mediated.

PMID- 8573341
TI  - New functions for gap junctions.
AB  - The most significant finding of the past year in gap junction research has been
      the association of connexin defects with human diseases. Connexin32 mutations
      cause X-linked Charcot-Marie-Tooth disease, a demyelinating peripheral
      neuropathy. Mutations in connexin43 may underlie cardiac malformations in
      visceroatrial heterotaxia syndromes. Genetic approaches and gene targeting have
      provided new insights, but also raise new questions concerning connexin function,
      the significance of connexin diversity and the regulation of intercellular
      communication.

PMID- 8573342
TI  - Plasmodesmata: intercellular channels for macromolecular transport in plants.
AB  - Plasmodesmata are special intercellular organelles that establish cytoplasmic and
      endomembrane (endoplasmic reticulum and nuclear envelope) continuity throughout
      most of the plant body. Microinjection studies have provided direct proof that
      plasmodesmata facilitate the cell-to-cell trafficking of viral movement proteins
      and nucleic acids. Evidence is now accumulating that plant-encoded proteins,
      including transcription factors, also move from cell to cell on this endogenous
      macromolecular trafficking pathway. The picture that is emerging is that the
      programming of plant development may involve this supracellular network for the
      effective delivery of one form of information molecule.

PMID- 8573343
TI  - Integrin transmembrane signaling and cytoskeletal control.
AB  - Integrins are remarkably multifunctional: they mediate cell adhesion and
      migration, orchestrate organization of the actin-based cytoskeleton, and activate
      signal transduction pathways. Recent studies have identified a variety of steps
      and hierarchies in these intracellular cytoskeletal and signaling responses,
      laying the groundwork for future studies on specificity and coordination with
      responses to growth factors.

PMID- 8573344
TI  - Leukocyte integrins.
AB  - Lymphocytes, monocytes and granulocytes, which are collectively known as
      'leukocytes', circulate primarily within the vascular system and lymphoid tissue
      but are found in essentially all tissues of the body. This mobile lifestyle
      necessitates the constant making and breaking of adhesive contacts with targets
      in their immediate environment. The adhesion receptors termed integrins, which
      are expressed in abundance by leukocytes, are well suited to carry out the
      transient interactions in which these cells engage. Major advances in the
      leukocyte integrin field this year have been the realization of the extensive
      roles for alpha 4 integrins in leukocyte function, the solution of the crystal
      structure of an I domain and its identification as a major ligand-binding site,
      and the initial understanding of how divalent cations may function in an active
      integrin.

PMID- 8573345
TI  - Adhesion in cell migration.
AB  - Adhesive interactions play a central role in cell migration. The regulation of
      these interactions requires the coordination of a multiplicity of signals, both
      spatially and temporally. The role of the integrin family has received
      considerable recent attention. Progress has been made in the elucidation of the
      mechanisms by which growth factors and other motogenic factors stimulate
      migration. Major advances have also been made in understanding the mechanisms by
      which the formation and breakdown of adhesive complexes are regulated, including
      the participation of members of the rho family. Despite these advances, many
      important questions remain, and the field seems well positioned to answer them.

PMID- 8573346
TI  - New insights into membrane dynamics from the analysis of cell surface
      interactions by physical methods.
AB  - The physical, chemical and mechanical properties of the cell surface can be
      probed using a variety of microscopy-based techniques. The movements of membrane
      components are currently being characterized, and recent experiments have begun
      to define the structural origins of these modes of transport at a molecular
      level. However, explicit relationships between new knowledge of membrane
      structure and complex, linked functions, such as signal transduction and
      adhesion, remain elusive.

PMID- 8573347
TI  - Inhibition of cell adhesion by anti-adhesive molecules.
AB  - The importance of inhibitory (as well as stimulatory) signals for cell adhesion
      and/or migration is most readily recognizable during development of the nervous
      system, where pathfinding and the avoidance of inappropriate tracks by axons in
      the periphery, and the development of organized layers and establishment of
      boundaries in the central nervous system are crucial events. Therefore, most of
      the recent progress concerning the identification of novel important
      extracellular molecules involved in repulsive and inhibitory interactions has
      been made by neurobiologists.

PMID- 8573348
TI  - New insights into the function of collagens from genetic analysis.
AB  - Recent studies utilizing transgenic approaches, in combination with mouse and
      human genetics, are leading to insights into the in vivo functions of fibrillar
      and non-fibrillar collagens. This information helps define the molecular causes
      of inherited disorders of connective tissues and provides answers to fundamental
      questions of tissue and organ morphogenesis.

PMID- 8573349
TI  - Proteolytic remodeling of extracellular matrix.
AB  - Matrix metalloproteinases and their natural inhibitors are ingredients of a
      fundamental cellular toolbox for effecting environmental change. These enzymes
      enable cells to alter their relationship to the environment by directly cleaving
      structural macromolecules of the extracellular matrix. In addition, evidence is
      emerging that they also play an important regulatory role in matrix remodeling by
      catalyzing the processing of inactive matrix metalloproteinase and cytokine
      precursors.

PMID- 8573351
TI  - Cell-to-cell contact and extracellular matrix.

PMID- 8573352
TI  - Detection and side-chain specificity of IgE antibodies to flucloxacillin in
      allergic subjects.
AB  - Unlike studies on the antigenicity of penicillins in laboratory animals, limited
      information is available on the allergenicity of penicillins in man, especially
      with regard to fine structural allergenic differences between the many different
      penicillins. Inconsistent with the earlier conclusions of others, our studies
      suggest that side-chain structures on the penicillin molecule are the major
      allergenic determinants in many reactions. Immediate allergic reactions to
      flucloxacillin were observed in a number of patients where diagnosis was
      confirmed by skin testing and detection of flucloxacillin-reactive IgE
      antibodies. Quantitative hapten inhibition studies revealed potent inhibition by
      flucloxacillin and three structurally related penicillins: oxacillin, cloxacillin
      and dicloxacillin. Analysis of the inhibition results showed that the side-chain
      group of flucloxacillin, 3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolyl, is
      recognized by some antibodies and that the 5-methyl-3-phenyl-4-isoxazolyl group,
      with or without halogen substituents, accounts for the reactivity of other
      antibodies and for the cross-reactions seen with some other penicillins. Since it
      is the side-chain group that distinguishes the many different penicillins, and
      since the side-chain groups are recognized by IgE antibodies in many of the
      allergic reactions, it is becoming clear that specific assays are required for
      the detection of IgE antibodies to each of the different penicillins.

PMID- 8573353
TI  - Changes in kinetic properties of oxytocin receptors in longitudinal muscle
      membranes of rat uterus during gestation.
AB  - Receptors of oxytocin were found to occur in the membrane fraction obtained from
      longitudinal muscle of pregnant rat uterus. The affinity of the membrane receptor
      for oxytocin increased through an increase in the association rate and a decrease
      in the dissociation rate during gestation. The membrane oxytocin receptor
      concentrations rose almost three-fold from Day 15 to Day 21. A transition of
      oxytocin receptors from a single class of independent sites to site-site
      interacted multiple binding sites, which most likely exhibit positive
      cooperativity during the last seven days of gestation, was observed. These
      results suggest that changes in the dynamics of uterine oxytocin receptors also
      play an important role in the onset of labor.

PMID- 8573354
TI  - Multiple molecular recognition properties of the lipocalin protein family.
AB  - The lipocalins, a diverse family of small extracellular ligand binding proteins,
      display a remarkable range of different molecular recognition properties. While
      their binding of small hydrophobic molecules, and to a lesser extent their
      binding to cell surface receptors, is well known, it is shown here that formation
      of macromolecular complexes is also a common feature of this family. Analysis of
      known crystallographic structures reveals that the lipocalins possess a conserved
      common structure: an antiparallel beta-barrel with a repeated +1 topology.
      Comparisons show that within this overall similarity the structure of individual
      proteins is specifically adapted to bind their particular ligands, forming a
      binding site from an internal cavity (within the barrel) and/or an external loop
      scaffold, which gives rise to different binding modes that reflects the need to
      accommodate ligands of different shape, size, and chemical structure. The
      architecture of the lipocalin fold suggests that both the ends and sides of this
      barrel are topologically distinct, differences also apparent in analyses of
      structural and sequence variation within the family. These differences can be
      linked to experimental evidence suggesting a possible functional dichotomy
      between the two ends of the lipocalin fold. The structurally invariant end of the
      molecule may be implicated in general binding to common cell surface receptors,
      while the more variable end is adapted to the specialised tasks of binding small
      ligands and forming macromolecular complexes via an exposed binding surface.

PMID- 8573350
TI  - A hierarchy of ECM-mediated signalling regulates tissue-specific gene expression.
AB  - A dynamic and reciprocal flow of information between cells and the extracellular
      matrix contributes significantly to the regulation of form and function in
      developing systems. Signals generated by the extracellular matrix do not act in
      isolation. Instead, they are processed within the context of global signalling
      hierarchies whose constituent inputs and outputs are constantly modulated by all
      the factors present in the cell's surrounding microenvironment. This is
      particularly evident in the mammary gland, where the construction and subsequent
      destruction of such a hierarchy regulates changes in tissue-specific gene
      expression, morphogenesis and apoptosis during each developmental cycle of
      pregnancy, lactation and involution.

PMID- 8573355
TI  - Unintended consequences: the dilemmas of shrinking the government.

PMID- 8573356
TI  - Support among smokers and nonsmokers for restrictions on smoking.
AB  - The responses of 387 smokers and 988 nonsmokers obtained in a population-based
      survey in Ontario, Canada, were compared with regard to knowledge, attitudes, and
      predicted behavior concerning restrictions on smoking. Responses were tabulated
      as percentages and weighted according to the sample design. Nonoverlapping 95%
      confidence intervals provided evidence to reject the null hypothesis. Although
      smokers were found to be less knowledgable about the health effects of smoking
      and environmental tobacco smoke, more than 90% of both smokers and nonsmokers
      agreed with restrictions on smoking in 14 specific settings; for some settings,
      they disagreed on the extent of restrictions. The groups differed concerning
      specific bans on cigarette sales, but support was uniformly strong for bans in
      hospitals, controls on vending machines, and enforcement of the law prohibiting
      sales to minors. Clear majorities of both groups agreed that local government
      should enact and enforce restrictions. Smokers were more likely than nonsmokers
      to predict that smokers would comply with more restrictions, and most smokers
      indicated that they, themselves, would comply. We conclude that general health
      education should be bolstered by strategies specifically targeted at smokers.
      There is a strong basis across the population for restrictions to reduce exposure
      to environmental tobacco smoke; support for the role of local government in this
      regard is clear. Noncompliance with more restrictions is unlikely to present
      enforcement problems. Measures limiting the physical access of youths to tobacco
      will be widely supported, but strategies to increase support for tax measures are
      needed.

PMID- 8573357
TI  - Compliance with primary prevention in private practice: creating a tobacco-free
      environment.
AB  - A sample of private orthodontic practices (n = 40) from a controlled trial for
      clinician-initiated tobacco-use prevention was used to test the effectiveness of
      preventive medicine representative (PMR) visits in creating and maintaining an
      anti-tobacco office environment. Clinical staff of 20 offices, randomly assigned
      to the experimental group, were trained by a PMR on the use of anti-tobacco
      materials (no-smoking signs, posters, and print materials). Twenty control-group
      offices did not receive any training or special treatment. Subsequently,
      experimental-group offices were visited by a PMR once every three months and were
      telephoned six weeks after each visit over a 12-month period. During visits and
      phone calls, PMRs prompted offices to order anti-tobacco materials. Visits served
      to introduce offices to new materials and to encourage their continued use. Data
      from direct observations and self-report measures showed significant differences
      between experimental and control offices for display of anti-tobacco materials at
      1.5 months and 12 months (P < .001). Results suggest that PMR visits may serve as
      an effective method of introducing and maintaining preventive medicine procedures
      in clinical environments.

PMID- 8573358
TI  - Association of education level with atherogenic diets in a rural biethnic
      population.
AB  - Better definition of dietary intakes among subpopulations will facilitate the
      implementation of relevant public health interventions. This study describes
      total calorie and macronutrient intake by level of education as reported by
      Hispanic and non-Hispanic white persons in the rural San Luis Valley of southern
      Colorado. Current diet was assessed for a geographically based sample of 552
      Hispanic and 754 non-Hispanic white (NHW) adults 30-74 years of age in two
      counties of rural southern Colorado 1984-1988). Diet was assessed by 24-hour
      recall. Hispanic men and women reported lower total calorie intakes at all ages
      than NHWs; however, the macronutrient composition was similar between groups
      (38.5% and 46.0% of calories from fat and carbohydrate, respectively). Ethnic
      differences in body size and reported physical activity did not account for
      ethnic differences in reported calorie intake. In both ethnic groups, subjects
      with more education reported higher calorie intake and less atherogenic diets
      (lower total fat, saturated fat, cholesterol, and Keys Index; higher
      polyunsaturated fat, P/S ratio, and total carbohydrate). In Hispanics and NHWs,
      lower education groups may require targeted interventions to decrease total fat,
      saturated fat, and cholesterol. Further study is needed to understand the ethnic
      difference in reported calorie intake.

PMID- 8573359
TI  - Ethnic differences in micronutrient intake in a rural biethnic population.
AB  - Differences in micronutrient intake have been observed between populations of
      differing socioeconomic status (SES) and ethnicity. This study reports
      micronutrient intake among Hispanic and non-Hispanic white (NHW) persons in the
      rural San Luis Valley of southern Colorado. Current diet was assessed for a
      geographically based sample of 552 Hispanic and 754 NHW adults 30-74 years of age
      in two counties of rural southern Colorado (1984-1988). Diet was assessed by 24
      hour recall. NHWs reported higher mean calorie intakes than Hispanics of both
      genders. NHWs had greater intakes of calcium, magnesium, potassium, phosphorus,
      riboflavin, niacin, zinc, vitamin A, and vitamin C than Hispanics, after
      accounting for ethnic differences in gender, age, and calorie intake. Differences
      in intake by gender were observed within and between ethnic groups. After
      adjusting for gender, age, ethnicity, and calories, we observed no statistically
      significant trends by SES measures. We conclude that diets of Hispanic adults
      would benefit from the addition of fresh fruits, vegetables, and high-calcium
      foods.

PMID- 8573360
TI  - Overweight and obesity in native-American adolescents: comparing nonreservation
      youths with African-American and Caucasian peers.
AB  - Previous studies have consistently shown that, compared to national standards,
      Native Americans across all age groups are disproportionately overweight or
      obese. Although most available data on rates of obesity in this group come from
      studies conducted on reservations, the proportion of Native Americans residing on
      reservation lands is rapidly declining. This study examines the prevalence of
      overweight and obesity in a population of Midwestern adolescents in public school
      settings and contrasts Caucasian and African-American adolescents with Native
      American youths of the same age. Data were derived from a secondary analysis of
      an anonymous health-risk survey. Height, weight, and ethnicity were ascertained
      through self-report. The results call into question whether rates of overweight
      or obesity in Native-American adolescents are disproportionate relative to those
      for Caucasian and African-American adolescents. Cumulative comparisons of all
      overweight and obese adolescents in the sample (n = 5,655) show significant
      differences among ethnic groups, but age-specific comparisons do not yield a
      consistent pattern, especially for Native-American girls. To compare the entire
      sample to national weight standards, we plotted mean body mass index (BMI) for
      each ethnic group by age against NHANES II reference data. Age-specific BMI means
      for Native-American and Caucasian girls fell largely below the NHANES II
      reference data. We present several explanations for these results. Given the
      study limitations, further objective study of the weight status of Native
      American children and adolescents in direct comparison with other ethnic groups
      is recommended.

PMID- 8573361
TI  - Breast screening by African-American women: insights from a household survey and
      focus groups.
AB  - This study uses quantitative and qualitative information to examine the
      relationships between predisposing, reinforcing, and enabling factors from a
      health education planning model and levels of mammography screening, clinical
      breast exam (CBE), and breast self-exam (BSE) among African-American women. We
      analyzed data from a random sample household survey of African-American women in
      a Florida community (n = 281) and three age-homogenous focus groups from the same
      population. Two thirds of the random sample and all of the focus group
      participants had less than a high school education and household incomes below
      $10,000. Even though both samples of women were likely to have a physician they
      see regularly, most had never had a mammogram and could not accurately describe
      more than two major techniques for BSE. Knowing guidelines for mammography, CBE,
      and BSE (predisposing factors), believing their screening behavior mattered to at
      least some family members (reinforcing factor), seeing a physician for health
      care and advice, and having been taught BSE in a physician's office (enabling
      factors) predicted one form of breast screening behavior or another in
      multivariate logistic regression analyses. In addition, knowing mammography and
      BSE guidelines and having been taught BSE in a physician's office were
      significant predictors of breast-screening behavior for both low- and moderate
      income women. Focus-group participants unanimously reported a willingness to
      listen to physician instructions regarding breast screening and to receive a
      mammogram if their physician recommended one. Both survey and focus group results
      emphasize the particular importance of physicians in promoting breast screening
      among African-American women regardless of their income.

PMID- 8573362
TI  - Increasing disparity in knowledge of cardiovascular disease risk factors and risk
      reduction strategies by socioeconomic status: implications for policymakers.
AB  - During the 1980s extensive local and national cardiovascular health promotion
      campaigns were implemented to improve knowledge of risk reduction. This study
      analyzed changes from 1980 to 1990 in knowledge of acquired cardiovascular risk
      factors (i.e., actual, objective knowledge of adverse lifestyle factors affecting
      cardiovascular health); perceived knowledge of risk-reduction strategies (i.e.,
      subjective knowledge about how to reduce the likelihood of cardiovascular
      disease); and interest in risk modification (i.e., interest in changing risk
      factor habits) by socioeconomic status using level of education. The study
      population included 2,455 women and men 25-74 years of age from three population
      based cross-sectional surveys in two northern California cities. We found
      significant differentials in baseline knowledge that widened over the 10-year
      study period, resulting in larger disparities across educational groups at the
      final survey in 1990 (P < .05). From 1980 to 1990, individuals with < 12 years of
      education experienced only slight improvement in their knowledge of
      cardiovascular risk factors (mean summary score of 4.4 increasing to 5.5, based
      on a 17-item questionnaire of risk factors); those with > or = 16 years of
      education experienced twice as much improvement (mean of 8.4 increasing to 11.1)
      (P < .05). There were similar time-effect disparities in knowledge of risk
      reduction strategies (P < .05). In contrast, interest in risk modification was
      high for all educational groups and remained uniform across time. The continuing
      and widening disparity in knowledge between socioeconomic groups suggests the
      need for policymakers to reform existing cardiovascular risk-reduction education
      campaigns.

PMID- 8573363
TI  - Reported treatment of hypercholesterolemia by family physicians in Sweden and
      Minnesota.
AB  - Swedish guidelines on treatment of hyperlipidemia recommend higher cut-off levels
      for initiating treatment than do American guidelines, but are virtually identical
      for instituting and performing therapy. The aim of this study was to compare
      family physicians' reported practices in Sweden and Minnesota. We selected random
      samples of family physicians in southern Sweden and Minnesota for telephone
      interviews. Participation rates were 236/264 (89%) and 183/209 (88%),
      respectively. Swedish and Minnesota physicians adhered to their guidelines on cut
      off levels in a case describing a 48-year-old man but, contrary to guidelines,
      reported higher cut-off levels for a 65-year-old man and a 65-year-old woman. In
      all cases described, Swedish physicians reported significantly higher cut-off
      levels. Swedish physicians were less prone to institute medication in older
      patients and less familiar with drugs. Minnesota physicians were more inclined to
      advise nicotinic acid derivatives (P < .0001 for all patient categories). Swedish
      physicians more frequently preferred resins (P = .00029) or fibrates (P = .0028)
      for the 48-year-old man and resins for the 65-year-old man (P = .0026). Despite
      common medical knowledge, the two medical communities are directed by different
      guidelines. Although adherence to cut-off levels was equally high in both groups,
      the use of lipid-lowering drugs has not become a familiar part of the therapeutic
      armamentarium for Swedish family physicians.

PMID- 8573365
TI  - Physician recognition of hypercholesterolemia in patients undergoing peripheral
      and carotid artery revascularization.
AB  - Numerous studies have shown that patients with peripheral and carotid
      atherosclerosis have a high prevalence of hyperlipidemia, and clinical trials
      using either angiography or ultrasonography have now demonstrated regression of
      both femoral and carotid arterial plaque during lipid-lowering therapy. However,
      whether patients with peripheral and carotid atherosclerosis receive adequate
      attention to lipid risk factors has not been studied. To evaluate physician
      recognition and management of hypercholesterolemia in these two patient
      populations, we reviewed the charts of 80 consecutive patients undergoing
      revascularization for symptomatic peripheral and carotid occlusive disease at a
      university medical center between 1990 and 1993. Physician practices were
      assessed for each patient by noting whether hypercholesterolemia was (1) screened
      for during the hospitalization and, if present, (2) documented as a problem, (3)
      managed in-hospital, or (4) given appropriate intervention at discharge. While
      73% of patients received some type of lipid case-finding perioperatively, less
      than one quarter of these were assessed for hyperlipidemia by the physician
      during the initial history. Moreover, of the 66% of screened patients found to be
      hypercholesterolemic, only 16% had documentation of the problem, only 24%
      received in-hospital management, and only 13% received intervention at discharge.
      These findings suggest that patients with documented peripheral and carotid
      atherosclerotic vascular disease probably receive inadequate attention to lipid
      risk factors and indicate the need for greater awareness and management of lipid
      disorders in these two patient populations by all involved physicians.

PMID- 8573364
TI  - Treatment and control of hypercholesterolemia and hypertension in persons with
      and without diabetes.
AB  - Our object was to examine whether the frequency of medical treatment for
      hypercholesterolemia or hypertension and the frequency of control of these
      conditions were different in persons with and without known diabetes. Subjects 43
      86 years of age with (n = 376) and without (n = 4,420) known diabetes
      participated in the Beaver Dam Eye Study. Hypercholesterolemia was defined as a
      serum cholesterol of > or = 6.2 mmol/L or use of lipid-lowering agents, and
      hypertension was defined as a systolic blood pressure > or = 140 mm Hg or
      diastolic blood pressure > or = 90 mm Hg or use of antihypertensive medications.
      Those subjects with diabetes had a similar frequency of hypercholesterolemia
      (42.8% versus 43.3%, P = .22) and a significantly higher frequency of
      hypertension (73.1% versus 48.3%, P < .0001) than those without diabetes. In
      those who were hypercholesterolemic, subjects with diabetes were slightly more
      likely to use lipid-lowering agents than those without diabetes (14.6% versus
      9.8%, P = .05). In those who were hypertensive, subjects with diabetes were more
      likely to be on antihypertensive medications than those without diabetes (77.4%
      versus 57.0%, P < .0001). After adjusting for sociodemographic and cardiovascular
      disease risk factors, the odds of a participant with hypercholesterolemia
      receiving treatment with lipid-lowering agents was 1.61 (95% confidence intervals
      [CI] = 0.98, 2.65) and the odds of a participant with hypertension receiving
      treatment with antihypertensive medications was 2.32 (95% CI = 1.68, 3.20) for
      those with diabetes versus those without.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8573366
TI  - Use of skin-cancer prevention strategies among farmers and their spouses.
AB  - Epidemiologic studies show that farmers are at increased risk of skin cancer,
      presumed to be secondary to the increased time they spend outdoors with exposure
      to the sun. We surveyed a random sample of farmers and their spouses 40 years of
      age or older from four rural counties in Michigan on their knowledge, attitudes,
      and behavior regarding protection of their skin from the sun and screening
      medical exams for skin cancer. Questionnaires were completed by 1,342 farmers and
      their spouses. This was a response rate of 63.5%. Eighty to ninety percent knew
      the changes in the skin that could indicate cancer and required medical follow
      up. Only 40% of the men and 65% of the women were likely to protect their skin
      when they went outdoors. Increasing age and personal history of skin cancer
      increased the likelihood of both men and women protecting their skin when they
      went outside. Additionally, higher-income women were likely to use sun
      protection. Despite the fact that 90% of the respondents had had a physical
      examination in the last three years, less than one third reported ever having had
      their skin examined for cancer. Increasing age, income, and education increased
      the likelihood of having had such an exam. The majority of those who had had a
      skin exam had the exam for a particular skin problem, and not as part of a
      routine physical examination. Farmers and their spouses need to increase their
      use of sun protection when going outside. Additionally, health care providers
      need to routinely include examination of the skin for skin cancer and alert their
      patients that it is being performed.

PMID- 8573367
TI  - Performance indicators for assessing competencies of preventive medicine
      residents.

PMID- 8573368
TI  - A direct association between HIV and AIDS in blood transfusion donors and
      recipients.

PMID- 8573369
TI  - Hydroxyurea and AIDS: an old drug finds a new application?

PMID- 8573370
TI  - Fine specificity of antibody recognition may predict amino acid substitution in
      the third variable region of gp120 during HIV type 1 infection.
AB  - To investigate how human immunodeficiency virus type 1 (HIV-1) escapes from
      antibodies directed against the neutralization domain in the third variable
      region (V3) of gp120, we examined precisely which amino acid contributed to
      antibody binding. From six HIV-1-infected individuals, sequential sera were
      tested for antibody binding to individually designed peptide panels. Each
      individual panel contained all V3 domain sequences of cloned HIV-1 variants
      obtained at several time points from the studied individual. We showed that the
      V3 domain is a major site for escape of the humoral immune response. We showed
      antibody binding was reduced by certain mutations in the V3 domain and sometimes
      concerted mutations rendered very distinct antigenic variants. The position and
      the number of the mutations that occurred during infection corresponded with the
      position and number of amino acids in the V3 domain that were important for
      binding to anti-V3 antibodies in the early immune response. The specificity of
      the antibody binding hardly changed during infection. Although mutations at
      several positions of the V3 domain reduced antibody binding, the mutations were
      limited to certain positions, probably because the function of the region has to
      be maintained. The amino acids that were important for binding in combination
      with the preference for changes at certain positions predicted to some extent the
      mutations that occurred later during infection.

PMID- 8573371
TI  - Random copolymers containing specific ratios of negatively charged and aromatic
      amino acids bind V3 disulfide loop and neutralize diverse HIV type 1 isolates.
AB  - Random copolymers of polyamino acids containing negatively charged and aromatic
      residues at specific ratios appear to bind HIV type 1 V3 loop and neutralize
      diverse laboratory isolates. At least the putative heparin binding domain and
      isoleucine residues in the amino half of V3 are involved in the interactions with
      these polymers. There are a number of interesting features common between these
      polymer's modes of binding to the V3 and the protease inhibition drug ABT-538.

PMID- 8573372
TI  - Maintenance of syncytium-inducing phenotype of HIV type 1 is associated with
      positively charged residues in the HIV type 1 gp120 V2 domain without fixed
      positions, elongation, or relocated N-linked glycosylation sites.
AB  - The prevalence of HIV-1 sequences of the envelope domains V1V2 and V3 was
      analyzed by RT-PCR amplification. Two distinct biological phenotypes of HIV-1
      have been described: the nonsyncytium-inducing (NSI) phenotype, best
      characterized by the inability to infect MT-2 cells, and the syncytium-inducing
      phenotype (SI), with the ability to infect MT-2 cells. Viral phenotype SI has
      been associated with HIV pathogenesis. The presence of positively charged amino
      acids at position 306 and 320 in the V3 domain of gp120 has been shown to be
      required for the support of the SI phenotype. In addition, V2 elongation and
      relocation of N-glycosylation sites were postulated to herald an NSI to SI
      phenotype switch. The present study was designed to assess the stability of an
      elongated V2 region with relocated N-glycosylation sites observed in SI isolates
      compared to NSI isolates. Eleven isolates with the SI phenotype and 19 isolates
      with the NSI phenotype were included in the study. Nine of the SI and 1 of the
      NSI isolates had a positively charged residue at position 306 or 320 (p < 0.001)
      in the V3 domain as assessed by direct sequencing of the viral RNA. In contrast,
      elongation and/or relocation of N-glycosylation sites of the V2 variable region
      were not found to be a consistent genetic feature of the SI phenotype. However,
      SI isolates had more positively charged amino acid residues in the hypervariable
      V2 region compared with NSI isolates. In one of the two SI isolates lacking
      positively charged amino acids at positions 306 or 320 in the V3 loop an
      elongation of 26 amino acids with 4 additional N-linked glycosylation sites was
      observed in the V2 region. This is consistent with the theory that elongation of
      V2 may be transiently required for SI conversion. These results suggest that
      maintenance of the SI phenotype requires positively charged amino acids in V3 in
      the majority of the virus population, but not an elongated V2 region with added
      or relocated N-linked glycosylation sites. Although increased charged residues in
      the V2 region may contribute.

PMID- 8573373
TI  - Antigenic analysis of HIV type 1 external envelope (Env) glycoprotein C2 region:
      implication for the structure of Env.
AB  - To determine whether the amino acid sequence extending from residue 273 to
      residue 288 in the second conserved region C2 of the HIV-1 envelope glycoprotein
      represents a target for antibodies on monomeric and oligomerized HIV-1 gp120env,
      we characterized several antisera and monoclonal antibodies (MAb) raised against
      C2 synthetic peptides. A cross-reactive epitope was evidenced on HIV-1Lai and HIV
      1Eli C2-derived peptides, but was not encountered on HIV-2 C2-derived peptide.
      This epitope was found to be expressed on the native monomeric gp120env but was
      not detected in the context of oligomeric Env, suggesting this region is
      sequestered in the oligomeric molecule. Preincubation of oligomeric Env with sCD4
      apparently failed to expose this epitope. Our results suggest that the amino acid
      sequence extending from residue 273 to residue 288 in C2 of HIV-1 gp120env may be
      involved in intermolecular interaction within the oligomeric Env complex.

PMID- 8573374
TI  - Induction of HIV type 1 neutralizing and env-CD4 blocking antibodies by
      immunization with genetically engineered HIV type 1-like particles containing
      unprocessed gp160 glycoproteins.
AB  - Genetically engineered, noninfectious HIV-1-like particles containing processed
      envelope glycoproteins represent potential candidate immunogens for a vaccine
      against HIV-1. However, since the gp120 glycoprotein is known to be rapidly lost
      from the surface of infected cells and purified virions as a result of its low
      affinity interaction with gp41, shedding of this extracellular subunit could
      compromise the immunogenic potential of particle-based HIV-1 vaccine candidates.
      In this study, we demonstrate for the first time the feasibility of producing
      fully assembled HIV-1-like particles containing only unprocessed gp160
      glycoproteins. Monkey kidney Vero cells were transfected with an inducible, human
      metallothionein-based expression vector containing most of the HIV-1LAI coding
      sequences that were genetically modified to introduce safety mutations and
      destroy the major cleavage site of the HIV-1 envelope glycoprotein. A stably
      transfected cell line was isolated and shown to secrete HIV-1-like particles
      containing unprocessed gp160. Immunization with these particles induced HIV-1
      cross-neutralizing, syncytium-inhibiting and env-CD4 blocking antibodies. Thus,
      these novel HIV-1-like particles represent alternative candidate immunogens for
      the development of a particle-based AIDS vaccine.

PMID- 8573376
TI  - Plasma viremia titration and RNA quantitation in ICD-p24 negative HIV type-1
      infected patients.
AB  - Quantitative culture of human immunodeficiency virus (HIV) was performed on 202
      plasma samples obtained from asymptomatic and early symptomatic HIV-1 infected
      patients (mean CD4+ count: 186/mm3) before antiretroviral therapy was started.
      HIV could be isolated from 84% of the plasma samples (titers ranging from 10(0)
      to 10(2.75) TCID50/ml). Immune complex dissociated p24 antigen (ICD-p24) was
      detected in 66% of the samples. Only 23 samples (11%) were negative for both ICD
      p24 as well as HIV culture. Discordant results were obtained in 55 samples, and
      45 samples negative for ICD-p24 were positive for HIV culture. A significant
      proportion (42%) of patients that were negative for ICD-p24 belonged to a very
      advanced group with very low CD4+ cell count. However, almost 90% of these ICD
      p24 negative samples were positive for HIV plasma viremia, stressing the value of
      this virological marker in patients with low CD4+ cell count and without any
      detectable ICD-p24 antigenemia. HIV-1 RNA was detected in all ICD-p24 negative
      plasma samples tested by the branched DNA (bDNA) assay. A very good correlation
      was found between high RNA copy number and HIV plasma isolation in samples
      obtained from patients with low CD4+ cell count, suggesting that HIV-1 RNA
      quantitation may also reflect viral infectivity of plasma.

PMID- 8573375
TI  - The genetic diversification of the HIV type 1 gag p17 gene in patients infected
      from a common source.
AB  - An evolutionary analysis was undertaken of HIV-1 gag p17 sequences taken from a
      small cohort of hemophilia B patients infected from a common batch of clotting
      factor concentrate. The sequence population found at seroconversion was highly
      homogeneous, suggesting that the infecting batch also contained little sequence
      variation. Genetic diversification was found in follow-up sequences taken
      approximately 3 years later and was generally found to be complex. Greater rates
      of synonymous to nonsynonymous substitution were observed, especially when
      comparing distantly related isolates, and the rate of synonymous substitution was
      used to estimate times of divergence for a number of isolates of HIV-1 including
      the origin of the subtypes A to H. The p17 region is therefore proposed as a
      useful marker for future epidemiological studies.

PMID- 8573377
TI  - Immunological characteristics of HIV-infected children: relationship to age, CD4
      counts, disease progression, and survival.
AB  - We have evaluated immunologic markers of disease progression in 79 children
      perinatally infected with HIV. Laboratory testing included T lymphocyte subsets
      and lymphoproliferative responses (LPR) to mitogens (PHA, Con A, and PWM),
      antigens (Candida, Tetanus), and alloantigens (MLC). Patients were graded into
      grades I, II, and III based on results of CD4 counts, and into grades A, B, and C
      based on results of LPR, with grades I and grades A being normal, III and C being
      the lowest, and II and B falling in-between. CD4 counts, CD4/CD8 ratio, and
      lymphoproliferative responses were markedly decreased in a majority of children.
      Grade III CD4 counts were almost always associated with decreased LPR. A majority
      of the children with grade I CD4 numbers, however, also had abnormal
      lymphoproliferative responses. Results of laboratory testing were analyzed in
      relation to clinical disease progression and survival. The first AIDS defining
      illnesses (ADI), especially opportunistic infections (OI), was usually associated
      with Grade III/C results in immunologic assays. Survival was significantly
      decreased in children with grade III CD4 cell counts, and grade C LPR, and was
      poorest if these abnormalities developed within the first year of life. In this
      latter age group, if the CD4 counts fell to grade III, the risk for dying was at
      least five times greater than those children with higher CD4 counts (grades II
      and I); if the proliferative responses to PHA and MLC were in Grade C, the
      survival was 22 months. Severe immune defects in the first year of life in
      children with HIV infection, as assessed by CD4 counts and a battery of
      functional tests, predicted rapid disease progression.

PMID- 8573378
TI  - The appearance of drug resistance-associated point mutations in HIV type 1 plasma
      RNA precedes their appearance in proviral DNA.
AB  - Point mutations in the reverse transcriptase (RT) gene of human immunodeficiency
      virus type-1 (HIV-1) have been associated with reduced sensitivity of the virus
      to inhibition by the antiretroviral drug zidovudine (ZDV). During therapy we have
      previously observed the accumulation of these mutations, at codons 41, 67, 70,
      215, and 219 of the RT gene, in proviral DNA sequences from infected peripheral
      blood mononuclear cells (PBMCs) and in cell-free virus RNA. Using a quantitative
      point mutation assay (PMA) we have been able to quantify the proportions of
      mutant and wild-type sequences at these points in mixed populations of viral RNA
      and DNA derived from clinical samples. Thus we have confirmed that the mutations
      can be detected earlier in cell-free virus RNA than in PBMC proviral DNA and
      their accumulation in RNA precedes that in DNA. We have analyzed serial samples
      from 10 subjects undergoing zidovudine therapy and shown significantly higher
      levels of mutations in cell-free viral RNA than in PBMC proviral DNA at codons
      41, 70, and 215 during the in vivo acquisition of the mutations. In the group of
      subjects studied the mean time delay between RNA and DNA reaching a given level
      of mutation was 25 days.

PMID- 8573379
TI  - Intracellular activation and cytotoxicity of three different combinations of 3'
      azido-3'-deoxythymidine and 2',3'-dideoxyinosine.
AB  - We measured the intracellular activation and cytotoxicity of 3'-azido-3'
      deoxythymidine (zidovudine, ZDV) and 2',3'-dideoxyinosine (ddI) when combined at
      three different clinically relevant combinations of 1:1, 1:10, and 10:1
      (ZDV:ddI). The activation of ddI to ddA-TP was increased in all three
      combinations with ZDV, compared to ddI alone. A maximum twofold increase in ddA
      TP was observed, which could not be further increased by raising the
      concentration of ZDV in the combination. On the other hand, the concentration of
      ZDV in the combination could be reduced to one-tenth while retaining increased
      activation of ddI. We also examined the cytotoxicity of these combinations in CEM
      cells, phytohemagglutinin (PHA)-stimulated and resting human peripheral blood
      mononuclear cells (PBMCs). CEM cells were the least sensitive overall to the
      drugs. ZDV showed greater cytotoxicity in stimulated PBMCs than resting PBMCs,
      whereas the reverse was true for ddI. This could be explained by the different
      activation pathways of these two drugs. The 1:1 and 10:1 ZDV:ddI combinations
      showed reduced toxicity compared to the separate drugs. These results indicate
      that ZDV and ddI need not necessarily be combined together at a ratio of ZDV:ddI
      of 1:1, but that some alteration in the dosages of ZDV or ddI in patients could
      be possible without loss of the benefits of combined ZDV:ddI therapy.

PMID- 8573380
TI  - Investigation of proviral load in individuals infected with human T-lymphotropic
      virus type II.
AB  - Human T-lymphotrophic virus type II (HTLV-II) has not yet been associated with
      any disease. Little is known about the proviral loads of HTLV-II in vivo and its
      relationship, if any, to lack of pathogenicity. We determined the HTLV-II
      proviral copy number in peripheral blood lymphocyte (PBL) samples from 49 HTLV-II
      infected individuals, of whom 25 were coinfected with human immunodeficiency
      virus type 1 (HIV-1). The HTLV-II copy numbers were determined by polymerase
      chain reaction (PCR) amplification of end-point dilutions of PBL lysates,
      followed by hybridization to a 32P-labeled HTLV-II-specific probe. The proviral
      copy number for the 49 samples ranged from < 0.02 to 200 per 1000 PBLs; 6% had <
      0.02, 16% had 0.02, 20% had 0.2, 18% had 2, 31% had 20, and 8% had 200 copies per
      1000 PBLs. The distributions of HTLV-II copy numbers in the coinfected and singly
      infected subgroups were not significantly different (Wilcoxon rank sum, p =
      0.24). In the coinfected subgroup, there was no significant correlation between
      the HTLV-II proviral load and the counts of CD4-positive lymphocytes or CD8
      positive lymphocytes (Spearman Coefficient = 0.26, p = 0.20; = 0.091, p = 0.67,
      respectively). Our data demonstrate the presence of a wide range of viral loads
      in HTLV-II-infected individuals. The high viral loads (> or = 20 copies/1000
      lymphocytes) detected in 39% of our samples suggest that the low pathogenicity of
      HTLV-II is not related to the presence of low viral loads in the infected
      subjects. Our data from the HIV-1 coinfected individuals show no apparent effect
      of HIV-1 on HTLV-II proviral loads.

PMID- 8573381
TI  - Human herpesvirus 6 variant A, but not variant B, infects EBV-positive B lymphoid
      cells, activating the latent EBV genome through a BZLF-1-dependent mechanism.
AB  - Human herpesvirus 6, a predominantly T lymphotropic virus, has been recently
      shown to infect some EBV-positive B cell lines, and to induce in them the
      activation of the EBV lytic cycle. Here we have confirmed and extended such
      observations, showing that (1) this phenomenon is restricted to the variant A of
      HHV-6: in fact two isolates belonging to the HHV-6 variant B (BA92 and Z29) were
      neither able to infect any B cell line, independently of the EBV status, nor to
      induce the EBV genome expression. The only exception is represented by the P3HR1
      cells, in which, however, the infection by the variant B does not determine
      induction of EBV antigens; (2) the presence of the EBV genome contributes to the
      susceptibility of the B cell lines to HHV-6 infection, increasing the binding
      sites and the percentage of infectable cells, as detected by immunoelectron
      microscopy; and (3) HHV-6 infected T cells, transfected with plasmids bearing the
      promoter regions of the EBV early genes BZLF1 and BMRF1, show a strong
      transactivation of these promoters.

PMID- 8573382
TI  - Regional distribution of lesions in the central nervous system of cats infected
      with feline immunodeficiency virus.
AB  - Neuropathological examination of the central nervous system of 13 naturally and
      13 experimentally feline immunodeficiency virus (FIV)-infected cats revealed
      diffuse gliosis of gray and white matter and vacuolar myelinopathy in a large
      proportion of infected animals, sometimes associated with lymphocytic meningitis.
      Multinucleated giant cell formation, the hallmark of multifocal giant cell
      encephalitis in HIV infection, was never observed. Morphometric analysis
      confirmed a marked increase of GFAP reactivity in infected cats. Gliosis was
      mainly present in cortical structures of frontal, parietal, and occipital lobes.
      Only one naturally infected animal evidenced clinical symptoms of neurological
      damage. This study confirms that FIV provides an interesting model for studying
      HIV-induced cortical and subcortical brain pathology believed to be the cause of
      the neurological manifestations frequently observed in AIDS patients.

PMID- 8573383
TI  - Molecular characterization of human T-lymphotropic virus, type 1 (HTLV-1) found
      in Kuwait: close similarity with HTLV-1 isolates originating from Mashhad, Iran.
AB  - Human T-lymphotropic virus, type 1 (HTLV-1) infection was detected in two
      unrelated Kuwaiti patients with tropical spastic paraparesis (HAM/TSP) and in the
      asymptomatic mother of one of them. The family roots of these patients were
      traced to the Najaf region of Iraq. The DNA sequence of three PCR-amplified
      fragments (env, 512 bp; pol, 140 bp; LTR, 704 bp) was determined for each of
      Kuwaiti HTLV-1 isolates (KUW-1,2,3). All three Kuwaiti HTLV-1 were identical in
      env and pol fragments and virtually identical in LTR. Two rare substitutions were
      found in the env and pol fragments. They were shared only with two isolates from
      Reunion Island (substitution in env), and two isolates from India and the
      Caribbean (substitution in pol). The sequences of env and pol fragments of the
      Middle Eastern HTLV-1 isolates were not available. However, the comparison of
      Kuwaiti isolates with representative Middle Eastern HTLV-1 was possible for the
      LTR fragment. The phylogenetic analysis of LTR sequences of KUW and 34 other HTLV
      1 isolates has shown that Kuwaiti HTLV-1 belongs to a cosmopolitan "a" subtype of
      HTLV-1 and tends to cluster together with HTLV-1 originating from the Mashhad
      region of Iran. These results suggest that common origin of Mashhadi and Kuwaiti
      (Najafi) HTLV-1 and the possibility of another pocket of HTLV-1 infection in the
      Middle East, located in the Najaf region of Iraq.

PMID- 8573384
TI  - Sequence analysis of simian T cell lymphoma/leukemia virus type 1 from naturally
      infected monkeys from central and west Africa reveals evolutionary conservation
      of immunogenic and neutralizing domains of gp46.

PMID- 8573385
TI  - Analysis of partial gag and env gene sequences of HIV type 1 strains from
      southern Africa.

PMID- 8573387
TI  - Conference on Advances in AIDS Vaccine Development: 7th annual meeting of the
      National Cooperative Vaccine Development Groups for AIDS. November 6-10, 1994.

PMID- 8573386
TI  - Identification of env subtypes in fourteen HIV type 1 isolates from south Africa.

PMID- 8573388
TI  - Suppression of activation of the human immunodeficiency virus long terminal
      repeat by CD8+ T cells is not lentivirus specific.
AB  - CD8+ T lymphocytes of HIV-1-infected individuals can efficiently suppress HIV-1
      replication in CD4+ T lymphocytes. To elucidate the molecular events underlying
      this suppression, we have used the HIV-1 LTR directing the chloramphenicol
      acetyltransferase gene (CAT) in transient transfection assays using human Jurkat
      T cells. In addition to supernatants of patient CD8+ T lymphocytes (CD4+ >
      350/microliters), supernatant of a T cell clone derived by Herpesvirus saimiri
      (HVS)-mediated transformation of CD8+ T lymphocytes of a patient demonstrating
      inhibition of virus replication were examined. Similar levels of inhibition of
      LTR-mediated gene expression in response to Tat or mitogenic activation with
      phorbol ester and calcium ionophore were observed by supernatants of both
      sources. The inhibitory effect of CD8+ T lymphocytes was not exclusive to
      lentiviral LTRs since transcription of both the HTLV-I LTR and RSV LTR in
      response to mitogen was effectively inhibited. In examination of the influence of
      CD8+ T cell-derived supernatant on NF kappa B-mediated activation, a dimer of the
      HIV-1 NF kappa B elements directing CAT was markedly inhibited by supernatants of
      both patient CD8+ lymphocytes and the HVS-derived CD8+ clone. Thus the inhibitory
      nature of CD8+ T lymphocytes appears not to be specific to lentiviral promoters
      and may mediate an inhibitory effect via the NF kappa B element.

PMID- 8573389
TI  - Expansion of CD11abright cells in CD8+CD45RA+ from HIV-infected patients: a new
      early marker for disease progression?
AB  - CD8+CD45RA+ T lymphocytes present two distinct subpopulations expressing the
      CD11a molecule (LFA-1 alpha chain) with different intensity. CD11adim cells
      represent the unprimed population within the CD8+CD45RA+ subset, whereas
      CD11abright cells are activated and may be considered as memory lymphocytes. The
      aim of this study was to analyze the expression of CD11a and CD18 within the
      CD8+CD45RA+ population in young HIV-infected individuals at different stages of
      disease as a marker of activation and of disease progression. Blood cells from 82
      HIV-infected individuals and 23 age-matched healthy controls were stained with
      unconjugated CD11a, CD18, PE-goat F(ab')2 anti-mouse, FITC-CD45RA, and TRI-Color
      CD8. Quantitative analysis for three-color immunofluorescence was carried out by
      flow cytometry. HIV+ subjects were subdivided into three groups according to
      their CD4+ cell number (group A, CD4+ cells > 500/microliters [20 subjects],
      group B, CD4+ cells between 500 and 200/microliters [36 subjects], and group C,
      CD4+ lymphocytes < 200/microliters [26 subjects]). We found a significant
      increase of CD11abright in the CD8+CD45RA+ subpopulation throughout the
      progression of the disease. The CD11abright percentage of positivity (mean)
      within the CD8+CD45RA+ subpopulation was 31% in healthy donors, 51% in group A,
      52% in group B, and 68% in group C. CD11abright expression was closely related to
      CD18bright (p < 0.001), but not to CD38. The relative increase of CD11a and CD18
      expression in CD8+CD45RA+ T lymphocytes parallels the decrease of CD4+ cells and
      the progression of disease: an inverse correlation between the percentages of
      CD4+ cells/microliter and CD8+CD45RA+CD11abright cells (p < 0.001) and a direct
      correlation between the number of CD4+ lymphocytes per microliter and both the
      number of CD8+CD45RA+CD11adim cells (p < 0.001) and the number of
      CD8+CD45RA+CD11abright (p = 0.002) was observed. The relative increase of
      CD8+CD45RA+CD11abright cells may represent an additional marker for monitoring
      HIV-induced immunodeficiency.

PMID- 8573390
TI  - Helper and cytotoxic T cell responses of HIV type 1-infected individuals to
      synthetic peptides of HIV type 1 Rev.
AB  - In cell-mediated immunity T cells recognize peptide fragments of the antigenic
      protein in association with major histocompatibility complex (MHC) proteins.
      Synthetic 9- to 16-mer peptides have been widely used to identify the region(s)
      of a protein that act as T cell epitope. Here, we report antigenic peptides
      identified on HIV-1 regulatory protein Rev. Four synthetic peptides (amino acids
      9-23, 25-39, 33-48, and 41-56) were first shown to stimulate T helper (Th) cell
      proliferation in peripheral blood lymphocytes (PBLs) derived from HIV
      seropositive (HIV+) individuals. The same peptides induced cytotoxic T lymphocyte
      (CTL) activities toward the autologous target cells incubated with the peptides.
      Both responses were specific to the HIV infection as HIV-seronegative (HIV-)
      control individuals showed no significant proliferative or cytotoxic activity.
      The proliferating cells were CD4+ T cells, and CTL activity was mediated by CD8+
      human leukocyte antigen (HLA)-restricted T cells. The identification of peptides
      containing epitopes that can induce both Th and CTL responses to regulatory
      proteins of HIV-1 in infected individuals might be important for vaccine
      development against AIDS. Since early regulatory proteins of HIV are expressed by
      the infected cells before the initiation of the synthesis of structural proteins,
      a CTL response against these proteins could destroy the infected cells before the
      release of infectious virions.

PMID- 8573391
TI  - Analysis of trans-dominant mutants of the HIV type 1 Rev protein for their
      ability to inhibit Rev function, HIV type 1 replication, and their use as anti
      HIV gene therapeutics.
AB  - The HIV-1 rev gene product facilitates the transport of singly spliced and
      unspliced HIV-1 transcripts and is necessary for productive HIV-1 infection. On
      the basis of the previously described trans-dominant Rev mutant M10, four point
      mutants and one frameshift mutant of the Rev protein were constructed. The
      mutants were inserted into retroviral expression vectors and analyzed for their
      ability to inhibit Rev-mediated gene expression. Transient transfection systems
      were used to screen these new mutants, and each was shown to inhibit expression
      of a Rev-dependent CAT reporter plasmid. Inhibition of HIV-1 envelope gene
      expression was tested in the HeLa-T4 cell line and was also shown to be inhibited
      by the trans-dominant Rev mutants. Retroviral vector producer cell lines were
      constructed and used to transduce Rev trans-dominant genes into the human T-cell
      line SupT1. The engineered SupT1 cell lines were then challenged with HIV-1 IIIB
      and HIV-1 expression was monitored by Northern blot analysis and in situ
      hybridization. SupT1 cells expressing either a Rev point mutant or the frameshift
      mutant showed greatly reduced HIV-1 mRNA accumulation and the Rev-dependent
      singly spliced and unspliced HIV-1 mRNAs were reduced. The kinetics of viral
      replication following challenge of Rev trans-dominant-engineered SupT1 cells with
      both HIV-1 IIIB and MN strains was significantly reduced and cells were protected
      from viral lysis. Viruses that emerge late in infection from Rev trans-dominant
      engineered cultures are not resistant to Rev-mediated inhibition. Last, trans
      dominant Rev-mediated protection of human CD4+ lymphocytes from challenge with
      primary HIV-1 patient isolates confirms the potential utility of this system as
      an anti-HIV-1 gene therapy approach.

PMID- 8573392
TI  - Inhibition of HIV type 1 Tat-mediated trans-activation by oncostatin M in HLtat
      cells.
AB  - We have tested the effect of oncostatin M (OSM) on the Tat-mediated trans
      activation in a HeLa cell line (HLtat) expressing Tat, using a transfection assay
      with the LacZ gene under the control of the HIV-1 LTR. Oncostatin M reduced the
      LacZ expression by 50% at a concentration of 9.5 ng/ml (IC50), which was far
      below the 50% cytotoxic concentration (CC50 > 400 ng/ml). Although HLtat cells
      may represent an interesting model for the study of the signal transduction
      pathway of OSM, this cytokine did not inhibit the tumor necrosis factor (TNF)
      dependent activation of the HIV LTR in Molt pNAZ cells or the Tat-mediated trans
      activation in HeLa, HeLa-CD4, Hep-II, COS-7, or Jurkat-tat cells. Likewise, OSM
      did not show any anti-HIV-1 activity in the MT4 cell/MTT assay. Our findings with
      OSM indicate that, for the screening of HIV Tat inhibitors, care must be taken in
      selecting a system that not only emulates HIV Tat trans-activation, but is also
      representative for in vivo-infected cells.

PMID- 8573393
TI  - Anti-Tat MTT assay: a novel anti-HIV drug screening system using the viral
      regulatory network of replication.
AB  - Since the recognition of its pivotal role in viral replication, Tat activity has
      become an interesting target for chemotherapeutic intervention of HIV infection.
      Here, we report a sensitive and simple colorimetric assay for the screening of
      Tat inhibitors. We have constructed a plasmid that contains the hygromycin B
      phosphotransferase gene under the control of the HIV-1 long terminal repeat (LTR)
      and HIV-1 tat gene constitutively expressed from the cytomegalovirus promoter.
      This plasmid has been stably transfected to the CD4+ T cell line CEM, which is
      rendered resistant to hygromycin B through the action of Tat. The inhibitory
      activity of the anti-Tat drugs was assessed by the extent of cytotoxicity in the
      presence of hygromycin B as a consequence of the suppressed expression of the
      hygromycin B phosphotransferase gene. Spectrophotometric quantitation of cell
      viability was done utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-
      diphenyltetrazolium bromide (MTT) dye as the indicator. Using this assay system,
      we have confirmed that known anti-Tat compound Ro5-3335 and its derivative Ro24
      7429 could inhibit Tat-mediated gene expression although their selectivities
      (anti-Tat activity versus nonselective cytotoxicity) were narrow. Since this
      method offers the advantage of not handling infectious particles or radioactive
      materials, it can offer wide applicability as a screening system for anti-Tat
      compounds.

PMID- 8573394
TI  - Function of exon 2 in optimal trans-activation by Tat of HIV type 2.
AB  - HIV-1 and HIV-2 are human retroviruses whose life cycles require viral regulatory
      proteins, one of which is the trans-activator, Tat. Tat of HIV-1 (Tat-1) displays
      modular function with independent activation function localized to the amino
      terminal, cysteine-rich, and core regions and independent RNA-binding function
      localized to a basic region. These functional domains are contained in the first
      of two exons encoding Tat-1; deletion of exon 2 does not contribute to functional
      domains of Tat-1. Tat of HIV-2 (Tat-2) has structurally analogous regions, but
      the amino terminus, basic region, and carboxy terminus encoded by exon 2 display
      amino acid sequence and functional divergence compared to Tat-1. We have shown
      that, in contrast to Tat-1, exon 2 of Tat-2 (residues 100 to 130) is required for
      optimal trans-activation of HIV-1 and HIV-2 long terminal repeats (LTRs). Here we
      demonstrate that a series of basic residues in exon 2 are required for these
      effects. Exon 2 does not alter the level of protein expression of Tat-2. Further,
      in the context of heterologous DNA binding, exon 2 does not contribute to
      activation function. These data suggest that full-length Tat-2 results in optimal
      trans-activation through enhanced RNA-binding function of exon 1 by involvement
      of a basic region in exon 2. Differential expression of short and full-length
      Tats during different stages of the HIV-2 life cycle might regulate levels of
      viral expression, viral replication, and resultant cytopathology.

PMID- 8573395
TI  - Structural modification of serum vitamin D3-binding protein and immunosuppression
      in AIDS patients.
AB  - A serum glycoprotein, vitamin D3-binding protein (Gc protein), can be converted
      by beta-galactosidase of stimulated B lymphocytes and sialidase of T lymphocytes
      to a potent macrophage-activating factor (MAF), a protein with N
      acetylgalactosamine as the remaining sugar moiety. Thus, Gc protein is a
      precursor for MAF. Treatment of purified Gc protein with immobilized beta
      galactosidase and sialidase generates an extremely high-titered MAF (GcMAF). When
      peripheral blood monocytes/macrophages of 46 HIV-infected patients were treated
      with GcMAF (100 pg/ml), the monocytes/macrophages of all patients were
      efficiently activated. However, the MAF precursor activity of plasma Gc protein
      was low in 16 (35%) of of these patients. Loss of the MAF precursor activity
      appeared to be due to deglycosylation of plasma Gc protein by alpha-N
      acetylgalactosaminidase found in the patient blood stream. Levels of plasma alpha
      N-acetylgalactosaminidase activity in individual patients had an inverse
      correlation with the MAF precursor activity of their plasma Gc protein. Thus,
      precursor activity of Gc protein and alpha-N-acetylgalactosaminidase activity in
      patient blood can serve as diagnostic and prognostic indices.

PMID- 8573396
TI  - Differential role of V3-specific antibodies in neutralization assays involving
      primary and laboratory-adapted isolates of HIV type 1.
AB  - To identify epitopes important in neutralizing primary HIV-1 isolates, we have
      selectively depleted HIV-1 sera of antibodies specific for the third
      hypervariable region (V3) of the HIV-1 envelope glycoprotein gp120, and then
      assessed the functional consequences of such depletion in neutralization assays.
      The nucleotide sequence of the V3 loop region from HIV-1 PBMC DNA was determined
      for three HIV-1-infected patients, corresponding peptides were synthesized, and
      then subsequently used for V3 depletion of the patient sera. Depletion using a
      single clade B V3 peptide was capable of depleting > 98% of binding antibodies to
      multiple clade B V3 peptides, including those with changes within the GPGX tip of
      the loop. Depleted and undepleted sera were studied for their ability to
      neutralize both laboratory-adapted HIV-1MN and two primary HIV-1 isolates with
      known V3 sequences, using a viral infectivity reduction assay. While the majority
      of HIV-1MN neutralization was lost on V3 depletion, the loss in neutralization
      capacity against primary isolates by these same V3-depleted sera was
      substantially less pronounced. This suggests that V3 peptide-specific antibodies
      within HIV-1 serum play a fundamentally different role in mediating
      neutralization in assays involving laboratory-adapted and primary isolates and
      implicates antibodies with epitope specificities outside of V3 as major
      determinants in neutralization assays involving primary isolates.

PMID- 8573397
TI  - Low anticoagulant heparin retains anti-HIV type 1 activity in vitro.
AB  - Heparin is a potent inhibitor of HIV-1 replication, in addition to being a well
      established inhibitor of blood coagulation. The major anticoagulant activity of
      heparin results from binding to the plasma protein antithrombin (AT). The high
      affinity binding site for AT is a specific pentasaccharide sequence that is of
      low abundance and completely absent from the majority of heparin chains. We have
      examined the anti-HIV-1 activity of both conventional and low molecular weight
      heparins fractionated according to affinity for AT. The high- and low-affinity
      fractions, despite differing markedly in anticoagulant activity, are identical in
      their ability to bind to the envelope glycoprotein of HIV-1, and in their
      inhibitory effect on HIV-1 replication in vitro (EC50 1 and 8 micrograms/ml for
      conventional and low molecular weight fractions, respectively). Our study shows
      that the anti-HIV activity of heparin is independent of its antithrombin-mediated
      inhibition of coagulation proteases. Therefore, heparin preparations retaining
      full anti-HIV-1 activity in vitro but with greatly reduced anticoagulant activity
      may be readily produced for further clinical investigation in the prophylaxis and
      therapy of HIV infection.

PMID- 8573398
TI  - Highly attenuated SIVmac142 is immunogenic but does not protect against SIVmac251
      challenge.
AB  - We report here the use of the highly attenuated SIVmac142 clone, unable to
      establish permanent infection of rhesus macaques, in a vaccine trial. Four rhesus
      macaques were immunized over a long time period with HUT-78 cells infected with
      wild-type SIVmac142 or, in order to reinforce the safety use of the vaccine, a
      deleted mutant with similar in vitro infectivity. The first two injections were
      done with living cells and the remaining boosts with cells emulsified in muramyl
      dipeptide adjuvant. Three control macaques were injected with uninfected HUT-78
      cells. Over 3 years, we have been unable except once to detect viral infections
      by three methods. However, antibodies directed against the viral Gag proteins and
      envelope glycoproteins were detected by immunoblots and/or in vitro
      neutralization assays. All macaques were challenged intravenously with a low dose
      (10 animal infectious doses) of a highly pathogenic biological clone of SIVmac251
      grown on macaque PBMCs. All seven animals became persistently viremic following
      challenge. The cell-associated viral loads of the vaccinated monkeys were not
      reduced relative to those of unvaccinated controls during the first weeks
      postchallenge even if vaccinated monkeys did not present a transient CD4
      decrease. Thus, our data reinforced the notion that the efficacy of live
      attenuated SIV requires the establishment of persistent infection.

PMID- 8573399
TI  - Identification of new genetic subtypes of human T cell leukemia virus type I in
      Gabon from encoding sequence of surface envelope glycoprotein.

PMID- 8573400
TI  - A computer program designed to screen rapidly for HIV type 1 intersubtype
      recombinant sequences.

PMID- 8573401
TI  - Topiary pruning of the HIV and SIV phylogenetic tree.

PMID- 8573402
TI  - HIV-1 subtype A in Canada.

PMID- 8573403
TI  - Identification of breakpoints in intergenotypic recombinants of HIV type 1 by
      bootscanning.

PMID- 8573404
TI  - Urinary excretion of type I collagen crosslinked N-telopeptides in healthy
      Japanese adults: age- and sex-related changes and reference limits.
AB  - A new immunoassay for measuring urinary excretion of type I collagen crosslinked
      N-telopeptides (NTx) has been reported to be a specific and sensitive method for
      assessing bone resorption. We have studied factors affecting biological
      variations in urinary NTx excretion in a population of 452 healthy Japanese
      adults, comprising 238 men and 214 women, 20-79 years of age. Urinary NTx
      excretion increased significantly with age in women (> or = 25 years of age) (r =
      0.55, p < 0.0001) and modestly correlated with lumbar bone mineral density (L
      BMD) in both sexes (> or = 25 years of age) (r = 0.31, p < 0.0001 for men; r =
      0.50, p < 0.0001 for women). Urinary NTx levels in women were significantly
      higher than in the corresponding male age groups after the fifth decade (p <
      0.0001). None of the anthropometric variables (weight, height, and body mass
      index) showed a linear effect on the urinary NTx excretion independent of age and
      L-BMD. In women, menopause was reflected by a twofold increase in urinary NTx
      excretion, from a mean of 28-59 pmol bone collagen equivalents (BCE)/mumol
      creatinine, and this menopause-related increase persisted for the entire
      postmenopausal period. In postmenopausal women, the interindividual variations of
      urinary NTx excretion were much more marked than in men and in premenopausal
      women. Moreover, in the subgroups of pre- and postmenopausal women, urinary NTx
      excretion correlated with neither age nor L-BMD. These data show that the major
      biological factor that modifies urinary NTx level is menopause and suggest that
      the bone turnover rates in the elderly women are increased, on average,
      irrespective of bone mineral density.

PMID- 8573405
TI  - Interleukin-1 immunoreactive nerves in heterotopic bone induced by DBM.
AB  - The occurrence of interleukin-1-positive nerves was investigated by
      immunohistochemistry in developing heterotopic bone, induced by demineralized
      allogeneic bone matrix (DBM) in the rat. Interleukin-1 immunoreactivity was
      observed 1 week after implantation and remained until the end of the experiment
      at 12 weeks. Immunoreactive material was first identified in mononuclear cells at
      day 7. Interleukin-1 immunoreactive nerve fibers were first observed in the
      fibrous tissue at 2 weeks after implantation. A maximum density of fibers was
      reached at 8 weeks. Abundant immunofluorescent fibers were observed in the marrow
      tissue of the ossicles, and also in the surrounding fibrous tissue. A substantial
      number were vascular, but in the bone marrow most of the nerve fibers appeared as
      irregularly arranged, non-vascular terminals with ramifications and varicosities,
      intermingled between the marrow cells. No fibers could be detected in the proper
      bone tissue. The distribution of interleukin-1-positive nerves in the ossicles
      strongly resembled that previously observed in rat long bones. Moreover, the
      shape and distribution of the fibers exhibited a striking similarity to that of
      noradrenergic fibers identified previously both in ossicles and normal rat long
      bones. The late occurrence and predominant distribution in marrow tissue would
      seem to imply that neuronal interleukin-1 does not participate in the early
      differentiation of bone cells. The most important finding seems to be the
      presence of interleukin-1-positive nerve terminals in blood vessel walls and
      amidst marrow cells.

PMID- 8573406
TI  - Height and body mass index in Oslo, Norway, compared to other regions of Europe:
      do they explain differences in the incidence of hip fracture? European Vertebral
      Osteoporosis Study Group.
AB  - Lean body stature and tallness have both been identified as risk factors for hip
      fracture. In this study, height and weight data from a multinational multicenter
      study were used to compare Oslo, which has some of the highest incidence rates of
      hip fracture ever reported, to other regions of Europe, with respect to height
      and body mass index. More than 17,000 subjects in six age strata (50-54, 55-59,
      60-64, 65-69, 70-74, 75+ years) from 36 centers in 19 European countries were
      enrolled in the European Vertebral Osteoporosis Study (EVOS), which included
      standardized height and weight measurements. We found that men in Oslo were 4.3
      cm taller than men in western Europe, 5.0 cm taller than men in eastern Europe,
      and 8.6 cm taller than men in southern Europe. Oslo women were also taller, by
      2.2 cm compared to women in western Europe, 2.7 cm compared to women in eastern
      Europe, and 5.2 cm compared to women in southern Europe. In all age groups,
      except women aged 55-59 years, mean body mass index (BMI) was lowest in Oslo.
      Nearly twice as many had a BMI less than 22.0 kg/m2 in Oslo compared to the other
      regions combined (11.1% vs. 6.6% in men and 19.2% vs. 9.9% in women). This study
      indicates that the people of Oslo are taller and leaner than people in other
      regions of Europe. This may in part explain the higher incidence of hip fracture
      in the population of Oslo.

PMID- 8573407
TI  - Bone mass, muscle strength, and different body constitutional parameters in
      adolescent boys with a low or moderate exercise level.
AB  - This study was conducted to evaluate the association between muscle strength of
      the thigh, different body constitutional parameters, and bone mineral density
      (BMD) in adolescents. The subjects were 26 healthy adolescent boys, age 15.9 +/-
      0.3 years, not training for more than 3 h per week. BMD was measured in total
      body, head, humerus, spine, femur, and tibia/fibula. Univariate correlations were
      measured between the explanatory parameters height, weight, body mass index
      (BMI), fat mass, lean body mass, quadriceps strength, hamstrings strength, and
      each BMD site using Pearson's coefficient of correlation. The explanatory
      variables were also used in a multivariate analysis to explain each BMD site.
      There was a high degree of concordance when comparing the two methods of
      analysis. Using the multivariate analysis, quadriceps strength and lean body mass
      showed significant independent correlations to all BMD sites measured, the
      correlations being stronger for the adjacent femur and tibia/fibula than for the
      distant humerus and head. Hamstrings strength correlated significantly and
      independently with tibia/fibula BMD and spine BMD. Fat mass, BMI, and weight
      correlated significantly and independently to all BMD sites except femur. This
      study demonstrates a general relationship between BMD and different body
      constitutional parameters and muscle strength of the thigh.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8573408
TI  - Mineral bioavailability and bone mineral contents in pigs given calcium carbonate
      postprandially.
AB  - We have further investigated the "meal effect" on mineral bioavailability in pigs
      by mineral balance studies and measurements of bone ash contents and bending
      moment. A group of seven pigs (CAA) was given all its dietary Ca as CaCO3 5 h
      after the first daily meal for 8 weeks. The control group of seven pigs received
      CaCO3 in the meal. Both groups were given normal P within the meals. Ca and P
      absorption and retention were evaluated by a 10-day balance trial. Several bones
      were collected at slaughter to determine bone ash, Ca, and P contents and bending
      moment (three-point bending test). Ingesting Ca after the meal did not affect Ca
      bioavailability or phosphorus absorption, but did reduce P retention, which in
      turn decreased the bone scores. Osteopenia, indicated by decreased total mineral
      contents of bones (and decreased ash:bone volume ratio), was associated with
      elevated plasma osteocalcin in the CAA group. Thus, CaCO3 need not be
      incorporated into a meal for high Ca absorption, provided that Ca is given after
      a meal, but simultaneous intakes of Ca and P are required for the best mineral
      retention.

PMID- 8573409
TI  - Quantitative ultrasound of the tibia: a novel approach for assessment of bone
      status.
AB  - An ultrasound instrument has recently been developed for the diagnosis and
      monitoring of osteoporosis (SoundScan 2000, Myriad Ultrasound Systems Ltd.,
      Israel). The instrument measures the speed of propagation of ultrasound waves
      (SOS, meters per second) along a fixed longitudinal distance of the cortical
      layer at the tibial shaft. Its in vivo precision is 0.25%. The performance of the
      SoundScan 2000 was studied in 307 Caucasian women (age range 24-87 years) who
      also had their bone mineral density (BMD) measured at the spine, femoral neck,
      and radial shaft by absorptiometric techniques. The SOS ranged from 3471-4226
      m/sec (mean 3867). The standardized coefficient of variation (CV), an expression
      of the effective clinical precision corrected for the spread of measurements
      (CV/[range/mean]), was 1.6% for the tibial SOS, compared to 1.5%, 3.8%, and 4.4%
      for spinal, femoral, and radial BMD, respectively. Tibial SOS significantly
      correlated with age (r = -0.52), time since menopause (r = -0.43), height (r =
      0.29), and weight (r = 0.16), as well as with BMD at the radius (r = 0.63), spine
      (r = 0.50), and femur (r = 0.47). After classification of bone measurements into
      tertiles, about 60% of the women with low tertile spinal BMD fell within the low
      tertile of either tibial SOS, femoral BMD, or radial BMD. The results show that
      measurement of tibial SOS is a precise method of assessing bone status without
      exposing the patient to sources of radiation.

PMID- 8573410
TI  - Estrogen and calcium supplement use among Japanese-American women: effects upon
      bone loss when used singly and in combination.
AB  - We examined the effects of estrogen and calcium supplementation upon bone loss
      among a cohort of Japanese-American women. The women averaged 64 years of age
      (age range 45-81) and 14 years postmenopause at their initial examination in
      1981. They returned at 1-3-year intervals for subsequent examinations, most
      recently in 1992-1994. At each examination, bone mass was measured at the
      calcaneus and distal and proximal radius. The women had low average dietary
      calcium intakes (median intake 384 mg/day). Women taking calcium supplements
      reported a median supplement intake of 355 mg/day; over 75% of the women taking
      estrogen took the equivalent of 0.6 mg/day or more of conjugated estrogens. Women
      taking estrogen had uniformly slower bone loss at all three sites. Compared to
      women not taking estrogen, whose bone loss averaged about 1% per year, women
      taking estrogen had 0.75-0.85% per year decreased bone loss at the three bone
      sites. By contrast, women who stopped estrogen had greater than average loss
      rates (0.35-0.65% per year greater). Calcium supplementation also reduced bone
      loss, but to a lesser extent than estrogen: bone loss decreased 0.25% per year at
      the radius sites, but was not slowed at the calcaneus. The calcaneus is more
      trabecular than the radius sites, which may explain the lack of response. We also
      examined combined estrogen and calcium supplement use.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8573411
TI  - Dextran sulfate promotes the rapid aggregation of porcine bone-marrow stromal
      cells.
AB  - Despite the fact that cells of the mammalian stromal compartment of bone marrow
      have been shown to contain multipotential stem cells when studied in diffusion
      chambers it is notable that the same range of possible phenotypes (e.g.,
      chondrocytic) has not been induced in freshly isolated marrow stromal cells in
      vitro. To investigate the possible role of glycoconjugates on phenotype
      expression, the effects of chondroitin sulfate, dermatan sulfate, dextran 500,
      and dextran sulfate on the cell morphology and differentiation of confluent
      porcine bone-marrow stromal-cell monolayers were studied. Of these
      glycosaminoglycan molecules only dextran sulfate induced confluent porcine bone
      marrow stromal-cell monolayers to retract into tight, circular cell aggregates.
      Retraction began within 6 h, was complete after 3-5 days, and was dose dependent.
      Subsequent removal of dextran sulfate from the culture medium resulted in a
      return to a monolayer culture. Aggregated cells were essentially nonmitotic but
      dye exclusion indicated high cell viability. Dexamethasone, ascorbate, and beta
      glycerophosphate produced no morphological change within 6 days when administered
      alone, but increased proliferation and aggregation in dextran sulfate-treated
      cultures. Immunocytochemistry of monolayer cultures revealed positive staining
      for type I but not type II collagen and addition of dexamethasone, ascorbate, and
      beta-glycerophosphate increased type I collagen deposition. In contrast, the
      centers of dextran sulfate-induced aggregates were positive for type II collagen,
      whereas type I collagen was only present at the periphery of the aggregates.
      Further addition of dexamethasone, ascorbate, and beta-glycerophosphate had
      little effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8573412
TI  - Effects of oral alendronate and intranasal salmon calcitonin on bone mass and
      biochemical markers of bone turnover in postmenopausal women with osteoporosis.
AB  - The main objective of this study was to determine the effect of daily oral
      alendronate treatment on bone mass in postmenopausal women affected by
      osteoporosis. The efficacy of intranasal salmon calcitonin was also examined.
      Nine centers in Italy enrolled 286 postmenopausal women between the ages of 48
      and 76 with spinal bone mineral density > or = 2 SD below adult mean peak in the
      two-year, double-blind, randomized, placebo-controlled trial. Patients were
      randomized to one of four treatment arms: double-blind placebo, alendronate 10
      mg/day, alendronate 20 mg/day, or open-label intranasal salmon calcitonin 100
      IU/day; all patients received 500 mg Ca++ supplements. Bone mass was measured by
      dual-energy x-ray absorptiometry every six months for two years. Patients who
      received alendronate 10 or 20 mg experienced significant increases in bone mass
      at all sites measured. At the end of the second year, the mean percent changes,
      for alendronate 10 and 20 mg relative to placebo, were 5.2% and 7.3% at the
      lumbar spine, 3.8% and 4.6% at the femoral neck, and 7.1% and 7.5% at the
      trochanter, respectively. In contrast, intranasal salmon calcitonin failed to
      increase bone mineral mass significantly at any site. Both alendronate doses
      significantly decreased serum alkaline phosphatase, serum osteocalcin, and
      urinary pyridinolines, markers of bone turnover, whereas placebo and intranasal
      calcitonin did not. Alendronate was generally well tolerated and no serious
      adverse events were attributed to its use.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8573413
TI  - Studies on two new vitamin D analogs, EB 1089 and KH 1060: effects on bone
      resorption and osteoclast recruitment in vitro.
AB  - We have investigated the effects on bone resorption of two new potent
      antiproliferative vitamin D3 analogs, EB 1089 and KH 1060, by studying
      recruitment of osteoclasts in murine bone marrow cultures and 45Ca release from
      prelabeled neonatal mouse calvarial bones. Binding studies to vitamin D receptor
      protein, from human osteosarcoma MG-63 cells, demonstrated kd values of 8.5 x 10(
      11) for 1 alpha,25(OH)2D3, 6.5 x 10(-11) for KH 1060, and 2.7 x 10(-10) for EB
      1089. 1 alpha,25(OH)2D3 and EB 1089 were equipotent stimulators of osteoclast
      recruitment in murine bone marrow cultures, with EC50 at 10(-10) mol/L, whereas
      KH 1060 was about tenfold more potent with an EC50 at 10(-11) mol/L. In serum
      free media, 1 alpha,25(OH)2D3 enhanced 45Ca release from neonatal mouse calvarial
      bones with EC50 at 10(-11) mol/L, but in the presence of 10% fetal calf serum
      (FCS) the stimulatory effect was significantly diminished, with a threshold value
      at 10(-10) mol/L. EB 1089 stimulated bone resorption with an estimated EC50 at 3
      x 10(-11) mol/L, whereas KH 1060 was about tenfold more potent than 1
      alpha,25(OH)2D3, and stimulated bone resorption with an EC50 at 10(-12) mol/L.
      The effects of EB 1089 and KH 1060 on 45Ca release were not significantly
      affected by the addition of 10% FCS. Addition of vitamin D binding protein to
      serum-free incubations of neonatal mouse calvarial bones, significantly inhibited
      the bone resorbing effect of 1 alpha,25(OH)2D3, but did not affect EB 1089 and KH
      1060 induced 45Ca release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8573414
TI  - Serum levels of carboxyterminal propeptide of type I procollagen and pyridinoline
      crosslinked telopeptide of type I collagen in normal children and children with
      growth hormone (GH) deficiency during GH therapy.
AB  - In this study, we investigated age-related changes in serum levels of both the
      carboxyterminal propeptide of type I procollagen (PICP) and the pyridinoline
      crosslinked telopeptide of type I collagen (ICTP) to elucidate bone formation and
      resorption, respectively, in 200 normal Japanese children (141 males and 59
      females, age range 0-16 years). Furthermore, to clarify the effect of GH on bone
      turnover, we measured serum PICP and ICTP in 26 growth hormone (GH)-deficient
      children (20 males and 6 females, age range 4-15 years) who showed significant
      bone growth during recombinant human GH therapy. In the normal children, the
      curves for age-related changes in both serum PICP and ICTP levels almost
      paralleled that of the standard height velocity curve in both sexes. The serum
      levels of both peptides were higher than those in adults, and the peak increases
      corresponded with the timing of the adolescent growth spurt. Furthermore, the
      serum levels of PICP and ICTP were significantly correlated with the height
      velocity. In the GH-deficient patients, the serum ICTP levels before GH therapy
      were lower than those in age- and sex-matched controls. Both PICP and ICTP levels
      in serum increased significantly at the beginning of GH therapy. Furthermore, the
      percent increase in PICP after 1 month of GH treatment was positively correlated
      with the percent increase in height velocity during 1 year of GH
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8573415
TI  - The (18-48)-fragment of human parathyroid hormone is a partial agonist for cAMP
      dependent actions with retained mitogenic function.
AB  - In the search of PTH agonists, PTH fragments were examined for both cAMP
      dependent and -independent actions on bone-derived assay systems. In a periosteal
      cell culture system from the embryonic chick, hPTH (18-48) was capable of
      inducing cell proliferation in a similar manner to hPTH (1-34) and hPTH (28-48)
      at picomolar concentrations, whereas hPTH (53-84) was inactive. Near
      physiological concentrations were needed for the proliferative action of PTH
      which seems to argue against a role for cAMP as a main mediator for growth
      response. In the tibiae organ culture system of embryonic chick cAMP stimulation
      and calcium mobilization requires micromolar concentrations. hPTH (18-48)
      produced, at a concentration of 10(-6) mol/L, a 14-fold increase in cAMP
      synthesis and an 11-fold increase in calcium mobilization and was 100-fold less
      active than hPTH (1-34). hPTH (28-48) and hPTH (53-84) had no significant effect.
      These results demonstrate that hPTH (18-48) retains the ability to induce cell
      proliferation and exhibits partial agonist activity in the cAMP/PKA signal
      transduction pathway.

PMID- 8573416
TI  - Marrow development and its relationship to bone formation in vivo: a histological
      study using an implantable titanium device in rabbits.
AB  - During embryogenesis, the creation of marrow sinusoids is intimately related to
      the coupled processes of osteogenesis and osteoclastic resorption. We set out to
      further define the relationship between bone formation and marrow development by
      implanting an intraosseous titanium device into the tibiae of rabbits which
      permits the examination of bone formation under standardized and reproducible
      conditions as well as allowing repeated sampling of new bone. A hollow channel is
      incorporated into the device into which tissue can grow. The device was left in
      place for 6 weeks to allow osseous integration to occur, after which the initial
      rod of new tissue growth was removed and subsequent histological and
      immunohistological sequence of events observed over the next 7 weeks.
      Interpretation of its morphological changes was further aided by concurrent
      histomorphometric studies. Because the channel was in direct continuity with the
      marrow cavity and isolated from the endosteum, immediate marrow regeneration was
      expected, following dissolution of the blood clot. Instead, our studies indicated
      that hemopoietic marrow cells, including the erythroid and myeloid series as well
      as megakaryocytes, did not appear until 3 weeks after implantation of the chamber
      when the newly formed bone had been remodeled to form an expanded marrow cavity.
      This intraosseous device is a useful in vivo model for studying the development
      of bone marrow hemopoietic and nonhemopoietic stromal cells and our results
      confirm the previous observation that influx of marrow cellular elements follow
      the formation of bone during endochondral as well as intramembranous
      ossification.

PMID- 8573417
TI  - Evaluation of technical factors affecting the quantification of trabecular bone
      structure using magnetic resonance imaging.
AB  - High resolution magnetic resonance (MR) techniques combined with standard
      techniques of stereology and texture analysis have been used to quantify
      trabecular structure. Using dried excised specimens from the tibia (n = 10) and
      radius (n = 2) we evaluate the impact of using volumetric gradient-echo (GE) and
      spin-echo (SE) MR imaging sequences, the relative importance of echo time in
      gradient-echo MR imaging, and the impact of different threshold values to segment
      the bone and bone marrow on the estimation of trabecular bone structure. We also
      investigate the inter-relationships between the different structural parameters
      derived from MR images. Images were obtained using fast gradient-echo and spin
      echo imaging sequences, with TE values ranging from 7 to 17 ms using 4.7 and 1.5
      Tesla imaging systems. In-plane image resolution ranged from 128 to 156 microns,
      and slice thickness ranged from 128 to 1000 microns. We derived stereological
      measures such as the mean intercept length, trabecular width, fractional area of
      trabecular bone, trabecular number, and trabecular spacing, the fractal dimension
      as a texture-related parameter and the Euler number as a measure of connectivity
      from these images. We found that the mean intercept length as a function of angle
      traced an ellipse with the orientation of the principal axis of the ellipse, a
      measure of trabecular orientation, identical when measured from the spin-echo or
      gradient-echo MR images. Absolute measures such as the fractional area,
      trabecular width, trabecular number, and fractal dimension as measured from
      gradient echo images were 28%, 30%, 1.3%, and 0.6% greater, respectively, than
      those calculated from spin-echo images, while the trabecular spacing was 14% less
      when calculated from gradient-echo images compared to spin-echo images. The
      structural parameters also depended on the echo time used to obtain the MR image.
      The choice of the threshold used to segment the high resolution images also
      affected the estimated structural parameters significantly. Our results indicate
      that MR may be used to visualize and quantify trabecular bone architecture;
      however, the different technical factors that could affect the appearance of MR
      images must be understood and considered in the data analysis and interpretation.

PMID- 8573418
TI  - Alterations to the en bloc basic fuchsin staining protocol for the demonstration
      of microdamage produced in vivo.
AB  - En bloc staining with basic fuchsin has become the method of choice to
      demonstrate bone microdamage produced in vivo. Several alterations have recently
      been made to the protocol. This technical note presents the new protocols, which
      include staining through a graded series of alcohols under vacuum, and
      eliminating the original evaporation stage in the staining protocol. Reasons for
      variations in staining quality can be related to inadequate dehydration, failure
      to stain under vacuum, the source of the basic fuchsin, or the solubility of
      basic fuchsin in water. The most common reasons for over- or understanding are
      the time left in stain, and the density of the bone. Limitations to the technique
      include the fact that probably not all cracks are stained by the technique, and
      the technique is not useful for studies that involve bone with highly variable
      densities in a single section.

PMID- 8573419
TI  - Standardization of postero-anterior (PA) spine BMD measurements by DXA. Committee
      for Standards in DXA.

PMID- 8573420
TI  - Tiludronate for Bone Diseases. Proceedings of a satellite symposium of the XIIth
      International Conference on Calcium Regulating Hormones (ICCRH). Melbourne,
      Australia, 14 February 1995.

PMID- 8573421
TI  - Tiludronate: bone pharmacology and safety.
AB  - The pharmacological properties of tiludronate (4-chlorophenyl)thiomethylene
      bisphosphonate), a sulfured bisphosphonate, have been characterized in a series
      of preclinical in vivo and in vitro studies. In vivo, tiludronate exerts a dose
      dependent inhibitory activity on bone resorption. This property was demonstrated
      in several animal models, including rats, ewes, and dogs, when bone resorption
      was induced by administration of retinoid acid or parathyroid hormone, or by
      immobilization, ovariectomy or orchidectomy. By uncoupling bone resorption from
      bone formation, tiludronate can induce a positive calcium and phosphate balance.
      When administered either continuously or intermittently to ovariectomized
      osteoporotic rats, tiludronate promotes a significant increase in bone mass. This
      positive effect is associated with an increase in mechanical resistance. Bone
      tolerance studies indicate that tiludronate is a safe compound with an
      appreciable therapeutic margin since it can effectively inhibit bone resorption
      without reducing bone mineralization and strength. In vitro, tiludronate added to
      bone tissue culture inhibits calcium release, lysosomal enzyme secretion and
      collagen matrix degradation when induced by various stimulators of bone
      resorption. At the cellular level, tiludronate does not appear to exert its
      inhibitory effect on bone resorption by impairing either the recruitment, the
      migration or the fusion of osteoclast precursors. Tiludronate could act on mature
      osteoclasts by reducing their capacity to secrete proton into the resorption
      space and also by favoring their detachment from the bone matrix. The available
      preclinical data indicate that tiludronate should be an efficacious
      bisphosphonate in the management of clinical conditions characterized by
      excessive bone resorption.

PMID- 8573422
TI  - Human pharmacokinetics of tiludronate.
AB  - Tiludronate is a bisphosphonate evaluated extensively as an osteoregulator in the
      treatment of metabolic bone disorders. It is highly polar and has a low and
      variable oral absorption similar to its related compounds. An absolute
      bioavailability of approximately 6% has been reported with large inter- and intra
      subject variability. The extent of absorption is increased at doses above 400 mg
      and may be reduced by a factor of 5 when tiludronate is administered with, or
      within 2 h after, food or dairy products. Approximately 90% of tiludronate is
      bound to serum albumin, and the binding is linear in the concentration range 1-10
      mg/L. Preliminary in vitro studies using human hepatocytes failed to show any
      evidence of biotransformation of tiludronate. The elimination half-life in
      patients with normal renal function is approximately 40-60 h, but is
      significantly increased in subjects with severe renal impairment. The renal
      clearance (0.7 L/h) is independent of dose and suggests that glomerular
      filtration is the mechanism responsible for elimination. Approximately 50% of the
      absorbed dose is bound to bone and the rate of release of the drug from this site
      is limited by bone turnover. In vitro experiments indicate that tiludronate is
      not an enzyme inducer or inhibitor. Drug interaction studies with the
      nonsteroidal agents acetylsalicylic acid, indomethacin, and diclofenac indicate
      that only with indomethacin was there any change in the pharmacokinetic
      parameters, and that these changes were minimal and unlikely to be of clinical
      significance. Tiludronate does not influence the pharmacokinetics of digoxin at
      steady state. Tiludronate appears to exhibit similar pharmacokinetic behavior to
      other bisphosphonates with the exception that its absolute bioavailability is
      significantly higher than that previously reported for clodronate and
      pamidronate. The impact of its pharmacokinetic properties on clinical outcome has
      yet to be determined.

PMID- 8573423
TI  - Efficacy and safety of drugs for Paget's disease of bone.
AB  - Paget's disease of bone is characterized by an anarchic bone turnover starting
      with excessive resorption caused by structural and functional abnormalities
      involving osteoclasts. Calcitonin and bisphosphonates are now considered as the
      main therapeutic approaches for this disease. Daily parenteral administration of
      calcitonin to patients with Paget's disease of bone results in a significant fall
      in serum alkaline phosphatase and urinary hydroxyproline levels. This treatment
      has also been reported to be effective in relieving clinical symptoms of the
      disease, mainly bone pain. The drawbacks of injectable calcitonin have stimulated
      interest in alternative routes of delivery. Substantial evidence of calcitonin
      bioavailability and bioefficacy equivalent to those of parenteral administration
      is currently available for only two alternative routes: nasal spray and rectal
      suppository. Since many results have been published showing a dramatic effect of
      several bisphosphonates in Paget's disease of bone, nasal and rectal calcitonin
      are no longer considered as the treatments of choice in this condition. A major
      advantage of the use of bisphosphonates over calcitonin in Paget's disease is
      that biochemical and histologic suppression of disease activity may persist for
      many years after the cessation of treatment. Oral etidronate and intravenous
      pamidronate have been extensively used and have provided satisfactory benefits to
      the patient. Since the risk/benefit ratio of alendronate does not appear to be
      completely positive, it is likely that the future of treatment of Paget's disease
      of bone will be based on the oral formulation of the new bisphosphonates,
      including tiludronate, risedronate or dimethyl-pamidronate.

PMID- 8573424
TI  - Therapeutic strategy in Paget's disease of bone.
AB  - Paget's disease of bone is a localized progressive disease, characterized by
      increased bone remodeling, bone hypertrophy, and abnormal bone structure, leading
      to pain and deformity. Disease complications involve the bones, joints, and
      central nervous system. Short-term treatment objectives are to alleviate or
      suppress bone pain; the long-term aim is for the prevention of complications
      caused by the slow disease progression in affected bones. The lifetime risk of
      complications depends on life expectancy, location, and activity index of Paget's
      disease. The use of potent and safe new bisphosphonates (tiludronate,
      pamidronate, alendronate, risedronate, and others) represents a major advance for
      the management of the condition: these compounds permit normalization of the
      biochemical indices of remodeling, and clinical doses have lasting effects
      without disruption to bone mineralization. Bone histomorphometry has shown that
      bisphosphonates can restore normal bone structure and an optimal therapeutic
      strategy should be defined. Symptomatic patients (or asymptomatic patients at
      risk) should be treated, as well as any patient requiring orthopedic surgery. The
      optimum strategy for preventing complications is to treat as early as possible
      and to halt disease progression by normalizing the biochemical markers that
      reflect the increased bone remodeling. There is no consensus on the threshold
      values for retreatment. Few studies have evaluated the long-term effects of the
      inhibitors of osteoclastic resorption on the risk of complications. A recent 12
      year, long-term follow-up of 41 cases of Paget's disease has shown that
      antipagetic therapy that did not normalize biochemical markers in 71% of patients
      did not prevent new complications in 62% of patients. These results suggest that
      an optimal regimen of treatment and retreatment should target normalization of
      biochemical markers of bone remodeling; the new bisphosphonates make this quite
      feasible in most patients.

PMID- 8573425
TI  - Tiludronate therapy for Paget's disease of bone.
AB  - A double-blind, randomized, placebo-controlled study was performed to evaluate
      the effect of oral tiludronate therapy in 139 patients with active Paget's
      disease of bone. Patients received placebo (N = 48), tiludronate 200 mg (N = 45),
      or tiludronate 400 mg (N = 46) once daily for 12 weeks. Biochemical and clinical
      responses were observed during the 12 week treatment phase and during an
      additional 12 week observation phase of the study. Both the 200 and 400 mg
      tiludronate groups experienced significant reduction in serum alkaline
      phosphatase (SAP) and urinary indices of bone resorption. After 12 weeks of
      therapy, the SAP levels decreased 46% from baseline values in the 200 mg group
      and 51% from baseline values in the 400 mg group. At the end of the 24 week
      study, SAP levels were reduced 47% and 58% from baseline in the 200 and 400 mg
      groups, respectively. The SAP reduction at 24 weeks was greater in the 400 mg
      group than the 200 mg group (p < 0.05). At the end of 24 weeks, 51% of patients
      treated with 200 mg and 72% of those who received 400 mg of tiludronate had
      experienced a reduction in SAP of greater than 50% (p = 0.043), and 7% and 35% of
      patients in the 200 and 400 mg groups, respectively, had experienced
      normalization of SAP (p = 0.001). There was no difference in incidence of side
      effects in patients taking tiludronate or placebo. In conclusion, oral
      tiludronate is an effective and well-tolerated therapy for patients with Paget's
      disease of bone. Daily therapy with 400 mg tiludronate for 12 weeks is more
      effective than a daily dose of 200 mg for 12 weeks.

PMID- 8573426
TI  - The methodology of clinical trials of oral tiludronate in Paget's disease of
      bone.
AB  - Tiludronate, a potent bisphosphonate, has been extensively evaluated in the
      treatment of Paget's disease of bone. Its ability to normalize bone turnover
      without impairing mineralization suggests that tiludronate represents an
      important therapeutic advance in the treatment of this progressive and disabling
      disease. Recent attention has focused on the development of appropriate short-
      and long-term treatment goals: namely the control of clinical symptoms, such as
      bone pain, and the reduction of bone turnover to within normal range, to lessen
      the risk of developing later complications, such as deafness, deformity and
      walking difficulties. This reduction of bone turnover is the primary aim of
      treatment. The clinical development of tiludronate has involved large-scale
      international multicenter trials. To allow the comparison of results obtained in
      a variety of clinical settings, great emphasis was placed on the use of
      consistent methodology across the program. This applied to patient selection,
      trial design, the evaluation of clinically meaningful effects of treatment and
      statistical analysis of results. Strict adherence to these principles has allowed
      us to compare the results of treatment with tiludronate in 85 centers in six
      countries across Europe. This paper illustrates the importance of clinical trial
      design in the evaluation of tiludronate and etidronate in the treatment of
      Paget's disease of bone, with a brief summary of results obtained from a recent
      comparative, prospective, double-blind, multicenter clinical trial. Effective
      suppression of bone turnover was assessed by monitoring the reduction in serum
      alkaline phosphatase and the ratio of urinary hydroxyproline/creatinine.
      Reduction in bone pain was assessed using Huskisson's visual analog scale. The
      results clearly show that tiludronate 400 mg/day for 3 months is more effective
      and as equally well tolerated as etidronate 400 mg/day.

PMID- 8573427
TI  - Skeletal safety of tiludronate.
AB  - The medical uses of bisphosphonates derive from their exceptional ability to
      inhibit bone resorption. However, bone resorption is essential for the healing of
      fractures, the repair of microscopic fatigue cracks in bone, nad the internal
      reorientation of trabecular and cortical bone in response to altered mechanical
      strains. In theory, overdose with bisphosphonates might interfere with the repair
      of fractures or weaken bone strength (by forcing bones to accumulate and
      propagate fatigue cracks or by abolishing the skeleton's adaptive powers).
      Regulatory agencies (particularly in the USA) have, therefore, set comprehensive
      and stringent safety criteria before the marketing of bisphosphonates can be
      approved. Some bisphosphonates can also inhibit bone mineralization, alter
      hepatic function, or cause gastritis/esophagitis. The safety profile of
      tiludronate will be described from this perspective, emphasizing the results of
      prolonged treatment in animals, and studies in humans.

PMID- 8573428
TI  - The worldwide problem of osteoporosis: insights afforded by epidemiology.
AB  - Osteoporosis is one of the major problems facing women and older people of both
      sexes. The morbid event in osteoporosis is fracture. However, the definition of
      osteoporosis should not require the presence of fractures but only a decrease in
      bone mass that is associated with an unacceptably high risk of fracture. In the
      USA, approximately 1.5 million fractures annually are attributable to
      osteoporosis: these include 700,000 vertebral fractures, 250,000 distal forearm
      (Colles') fractures, 250,000 hip fractures, and 300,000 fractures of other limb
      sites. The lifetime risk of fractures of the spine (symptomatic), hip, and distal
      radius is 40% for white women and 13% for white men from 50 years of age onwards.
      Following a hip fracture, there is a 10%-20% mortality over the subsequent 6
      months, 50% of sufferers will be unable to walk without assistance, and 25% will
      require long-term domiciliary care. Contrary to prevailing opinion, the morbidity
      and suffering associated with wrist and spine fractures are also considerable.
      The annual cost of osteoporosis to the US healthcare system is at least $5-$10
      billion with similar incidence and cost in other developed countries. These
      already high costs will increase further with continued aging of the population.
      In addition, the population explosion in underdeveloped countries will change the
      demography of osteoporosis; for example, the incidence of hip fracture, and,
      presumably, other osteoporotic fractures will increase four-fold worldwide during
      the next 50 years and the attendant costs will threaten the viability of the
      healthcare systems of many countries. Unless decisive steps for preventive
      intervention are taken now, a catastrophic global epidemic of osteoporosis seems
      inevitable.

PMID- 8573429
TI  - Osteoporosis: diagnosis and management today and tomorrow.
AB  - Osteoporosis is a disease in which low bone mass and microarchitectural
      deterioration of bone tissue lead to increased bone fragility and a consequent
      increase in fracture risk. The risk of developing osteoporosis can be assessed by
      determining the maximum density and strength achieved at maturity (peak bone
      mass) and the rate and duration of age-associated bone loss. The major cause of
      osteoporosis is estrogen withdrawal in women, most commonly associated with the
      menopause, but also with other causes of ovarian failure. Androgen insufficiency
      in men, although much less common, can also lead to osteoporosis. Measurements of
      bone mineral density (BMD) have been used to predict fractures, and current
      evidence suggests that fractures at any site can be predicted by taking
      measurements of BMD at any other site in the skeleton, using noninvasive
      techniques such as single or dual energy absorptiometry, quantitative computed
      tomography and ultrasound, a promising but experimental approach. Rapid bone loss
      at the start of the menopause is also an important contributing factor to the
      development of osteoporosis. Levels of biochemical markers of bone turnover in
      plasma and urine have been found to correlate with rapid and prolonged bone loss.
      Powerful new assays for estimating bone turnover have emerged and more are being
      developed. Various combinations of these biochemical tests may be used in
      conjunction with bone densitometry to predict future risk of osteoporosis and
      osteoporosis-related fractures. Furthermore, biochemical tests can also be useful
      in assessing response to therapy. Although many factors, including sex, race,
      heredity and lifestyle (e.g., calcium intake, minerals, nutrition and exercise),
      influence the risk of osteoporosis, i.e., they affect peak bone mass and
      subsequent bone loss, and are of little use in predicting future occurrence.

PMID- 8573430
TI  - Tiludronate: development as an osteoporosis therapy.
AB  - The clinical development of tiludronate (tiludronic acid, disodium salt) for the
      treatment of Paget's disease of bone is now being complemented by another
      clinical trials program to investigate its use in osteoporosis. It is expected
      that osteoporosis will become a major indication for tiludronate, and this paper
      describes the trial design and treatment goals that will be employed in these new
      studies. In studies to assess the incidence of fracture, the primary efficacy end
      point is the occurrence of vertebral fractures after 3 years of therapy.
      Secondary end-points include changes in lumbar bone mineral density, spinal
      deformity index, and height. Changes in biochemical markers and quality of life
      will also be assessed. Safety evaluations include clinical laboratory parameters,
      adverse events and, in selected patients, histomorphometry of the iliac crest
      bone. For the nonfracture studies, the primary efficacy end-point is the effect
      on bone mineral density after 2 years of therapy. Secondary end-points include
      vertebral fracture rate, spinal deformity index, and height. Biochemical markers,
      quality of life, and safety (including bone biopsies in selected patients) will
      be evaluated as in the fracture studies. The studies are expected to be completed
      in early 1997, followed by worldwide regulatory applications in late 1997.

PMID- 8573431
TI  - Diagnostic language and the meaning of collaboration.

PMID- 8573432
TI  - You make the diagnosis: case study. Biases that influence the diagnostic process.

PMID- 8573433
TI  - Mixed incontinence: a new nursing diagnosis?
AB  - Consistent efforts to identify and clinically validate new nursing diagnosis
      within recognized categories are essential to taxonomy development. Mixed
      incontinence is a clinical condition resulting in leakage of urine associated
      with increased intra-abdominal pressure (stress) and inability to delay voiding
      (urge). The presence of mixed incontinence was clinically validated in two
      populations (n = 9, n = 40) of community-dwelling women and initial defining
      characteristics were identified. Research findings from both studies support the
      addition of a proposed sixth nursing diagnosis, mixed incontinence, to the
      diagnostic category, alteration in urinary elimination.

PMID- 8573434
TI  - High frequency: treatment priority nursing diagnoses in critical care.
AB  - The purpose of this study was to identify high frequency-treatment priority
      nursing diagnoses in critical care nursing using survey research methods. Through
      a mailed survey the prevalence of 135 nursing diagnoses from the NANDA Diagnostic
      Taxonomy and other diagnoses was rated by a national, random sample of 678
      critical care nurses. Six important diagnostic areas were: sleep-rest, activity,
      nutritional-metabolic, cognitive-perceptual, self-perception (mood state), and
      health management (risk) patterns. Twenty diagnoses were rated as nearly always
      or frequently present in their practice by 70% or more of the nurses. Findings
      can be used to focus clinical studies of the highly prevalent diagnoses.

PMID- 8573435
TI  - Diagnoses of the human response pattern, communicating: a proposal for revision.
AB  - The authors present an analysis of the concept of communication, and propose a
      revision of NANDA's taxonomic human response pattern communicating, and its
      nursing diagnosis, impaired verbal communication. The authors recommend that the
      definitions of the human response pattern and its diagnosis be modified to
      incorporate facets other than verbal emissions. The addition of new defining
      characteristics and related factors also should be considered. New defining
      characteristics could include modifications of criteria of the American Speech
      and Hearing Association, highlighting disturbances in speech, language, hearing,
      and vision in addition to some of the present NANDA defining characteristics.
      Proposed related factors are classified as alterations in human patterns
      (developmental, physiological, psychological, social, cultural and
      environmental).

PMID- 8573437
TI  - Where are we going? Nursing diagnosis in education.

PMID- 8573436
TI  - An analysis of the nursing diagnosis ineffective management of therapeutic
      regimen compared to noncompliance and Orem's self-care deficit theory of nursing.
AB  - The authors compare the nursing diagnosis ineffective management of therapeutic
      regimen with that of noncompliance and with Orem's concept of self-care deficit.
      The article describes how the diagnosis of ineffective management of therapeutic
      regimen is more comprehensive than noncompliance. A question of patient autonomy
      is raised considering how the patient manages his or her therapeutic regimen. The
      major conclusion is that the nursing diagnosis of ineffective management of
      therapeutic regimen is based on continuous interaction between patient and nurse.
      The authors recommend that noncompliance be eliminated as a nursing diagnosis.

PMID- 8573438
TI  - Hereditary Breast, Ovarian, and Colon Cancer. Proceedings of a workshop.
      Washington, D.C., April 27-29, 1994.

PMID- 8573439
TI  - Translational research on hereditary colon, breast, and ovarian cancers.
AB  - Discoveries of inherited cancer susceptibility genes are creating new
      opportunities for translational cancer control research. Identification of these
      genes was facilitated by epidemiologic studies of mendelian patterns of cancers
      in families and advances in laboratory techniques to detect inherited mutations.
      Tumor suppressor genes were the first cancer-predisposing genes identified,
      primarily through studies of rare cancers such as hereditary retinoblastoma and
      Wilms' tumor. Recently, a second class of susceptibility genes, mismatch repair
      genes such as MSH2 and MLH1, has been shown to be defective in hereditary
      nonpolyposis colon cancers. Knowledge of these genes and the recently identified
      BRCA1 gene for hereditary breast/ovarian cancers raises the possibility of cancer
      predisposition testing of substantial portions of the general population.
      Carriers are at high risk of cancer and are candidates for early detection and
      chemoprevention studies. However, large-scale cancer-predisposition testing poses
      questions about not only ethical, legal, and social issues, but also
      technological and logistical challenges. Cancer-predisposition testing is new,
      and research is needed to maximize benefits while minimizing risks.

PMID- 8573440
TI  - Developing intervention/prevention strategies for individuals at high risk of
      developing hereditary ovarian cancer.
AB  - In 1994, an estimated 24,000 new cases of ovarian cancer will be diagnosed in the
      United States. Most of these patients will have disease spread beyond the ovary
      at the time of diagnosis; despite tumor debulking and aggressive platinum-based
      chemotherapy, their long-term prognosis is poor. In view of the advanced stage of
      disease at the time of diagnosis and the poor results of conventional therapy,
      advances in early detection and/or prevention are desperately needed. The recent
      recognition that a family history of the disease is perhaps the strongest risk
      factor for the development of ovarian cancer offers a unique opportunity to
      identify women at high risk for ovarian cancer and to develop effective screening
      methods and prevention/intervention strategies for these high-risk women. The
      results of the breakout session "Developing Strategies for
      Intervention/Prevention Trials for Individuals at Risk of Hereditary Ovarian
      Cancer" are summarized here. The majority of the discussion in this session
      focused on three major issues: 1) identification of moderate- and high-risk
      individuals who would potentially benefit from screening, prevention, and
      intervention efforts; 2) assessment of the effectiveness of current screening
      modalities and the usefulness of current intervention/prevention strategies; and
      3) recommendations for clinical trial design.

PMID- 8573441
TI  - Developing strategies for intervention/prevention trials of individuals at risk
      of hereditary colon cancer.
AB  - Environmental causes are thought to be the etiology of most colorectal cancers
      (sporadic colorectal cancer). However, about 10% of the cases result from one of
      two well-defined forms of hereditary colorectal cancer: hereditary nonpolyposis
      colorectal cancer and familial adenomatous polyposis. The development of
      intervention/prevention strategies for patients with newly diagnosed colon cancer
      and their families at high risk for hereditary colon cancer was framed in the
      questions: "Who is the target?" and "How to identify those at high risk"? There
      is agreement that genetic analysis for hereditary colorectal cancer holds
      tremendous promise but that it requires the development of highly structured
      protocols to ensure that genetic testing is a positive experience for patients at
      high risk. Appropriate strategies to identify high-risk patients would include
      recruiting minority (ethnic, racial, and socioeconomic) populations into these
      studies. Implementation of the protocol would begin with primary-care physicians
      working with cancer prevention centers in a network to achieve informed consent,
      to obtain bank-blood samples for genotyping, and to provide the social support
      and genetic counseling necessary to achieve the goal of a positive experience in
      cancer prevention. Initial studies would be directed at the known hereditary
      colorectal cancer groups, including familial adenomatous polyposis and hereditary
      nonpolyposis colorectal cancer.

PMID- 8573442
TI  - Evaluating children and adolescents for heritable cancer risk.

PMID- 8573443
TI  - Testing and counseling adults for heritable cancer risk.
AB  - A summary of recommendations from a breakout session of a Workshop on Hereditary
      Breast, Ovarian and Colon Cancer held in Washington, DC, in April 1994 is
      presented here. The focus of the session was the provision of testing and
      counseling services for adults at increased risk for developing cancer. Elements
      of service provision involving three time-points for counseling (pretest
      education, risk notification, and follow-up) and suggested areas of research are
      outlined for discussion.

PMID- 8573444
TI  - Patient-provider relationship in the context of genetic testing for hereditary
      cancers.

PMID- 8573445
TI  - Advocate participation in the context of genetic testing for hereditary cancers.

PMID- 8573447
TI  - Genomic imprinting, DNA methylation, and cancer.

PMID- 8573446
TI  - A 45-year follow-up of kindred 107 and the search for BRCA2.
AB  - Interest in the genetics of breast cancer has intensified with the discovery of a
      breast cancer susceptibility locus, BRCA1, on chromosome 17q. In this paper, we
      describe updated information on a large breast cancer kindred (K107) that has
      been extensively studied since 1948. Specifically, we have identified many new
      cases of cancer in the family and have shown that this family is unlinked to
      BRCA1 as well as a number of other genes considered as candidates for breast
      cancer. In a collaborative study between the University of Utah and the Institute
      of Cancer Research in the United Kingdom, we have collected a set of families
      with a predisposition to breast and ovarian cancers that have been reliably
      excluded from linkage to BRCA1 and evaluated their usage in a genomic search for
      other breast cancer loci. This effort led to the discovery of a second breast
      cancer locus located on chromosome 13q, BRCA2, which is responsible for the
      increased incidence of breast cancer in Kindred 107.

PMID- 8573448
TI  - Molecular markers in cancer diagnosis.
AB  - Clonal genetic alterations are a hallmark of human cancer pathogenesis. These
      genetic alterations may include specific gene mutations that drive the cancer
      process or phenotypic changes such as microsatellite instability that may be
      caused by specific genetic events. Identification of clonal cell populations that
      share a specific genetic alteration is virtually synonymous with the detection of
      cancer. These clonal cells can be detected among a large population of normal
      cells from limited clinical samples by DNA amplification techniques. Because of
      their unprecedented sensitivity and specificity, these approaches offer new hope
      for the early diagnosis of human cancer.

PMID- 8573449
TI  - Surgical prophylaxis of familial colon cancer: prevention of death from familial
      colorectal cancer.
AB  - Patients at risk for inherited colorectal cancer constitute a heterogeneous
      population. A total colectomy is minimal treatment for those patients with
      invasive cancer or those with established risk factors. For others at risk,
      predictive genetic markers, correlated with clinical and pathologic determinants,
      will establish the basis for policies of surveillance and preventive surgery.

PMID- 8573450
TI  - Prophylactic oophorectomy in inherited breast/ovarian cancer families.
AB  - Prophylactic oophorectomy is chosen by some women at high risk of ovarian cancer
      due to inherited predisposition. Unfortunately, this surgery is not 100%
      effective in preventing intra-abdominal carcinomatosis that histologically
      resembles ovarian cancer. To determine the incidence of post-oophorectomy
      carcinomatosis and to quantify the effectiveness of preventive surgery, a
      multicenter study is ongoing between the National Cancer Institute (NCI),
      Creighton University, and the United Kingdom. The prospective incidence of
      malignancy, especially of tissues derived from coelomic epithelium (primarily
      ovary, fallopian tube, and peritoneum), was compared between women of similar
      genetic risk who have or have not undergone oophorectomy. Analysis of 12 NCI
      families has been completed. Prospective observation ran from the date of family
      ascertainment until the date of cancer incidence, death, or December 31, 1992.
      Approximately 1600 person-years of observation occurred among 346 first-degree
      relatives of a breast or ovarian cancer case patient for women who had not
      undergone oophorectomy. Eight ovarian cancers occurred, compared with two
      carcinomatosis cases during 460 person-years of observation among 44
      oophorectomized women. Compared with Connecticut Tumor Registry data adjusted for
      age, race, and birth cohort, there was an approximately 24-fold excess of ovarian
      cancer among non-oophorectomized women and a 13-fold excess of "ovarian" cancer
      among oophorectomized women, though this difference was not statistically
      significant. The confidence intervals around these numbers were large, and a
      collaborative analysis will be required to determine whether this apparent
      protective effect is real.

PMID- 8573451
TI  - Bilateral prophylactic mastectomy: issues and concerns.
AB  - At present, the care of women at increased risk of developing breast cancer poses
      a clinical dilemma and remains an area of controversy. A number of investigators
      have addressed the pros and cons of prophylactic mastectomy versus close follow
      up, utilizing annual mammography, semiannual or even more frequent physical
      examinations of the breast, and proficient monthly breast self-examinations.
      Recent efforts to isolate a gene (BRCA1) on chromosome 17q12-21 raise additional
      concerns about the management of women testing positive for BRCA1 mutations.
      These women are estimated to have an 85% lifetime risk of developing breast
      cancer. Testing for BRCA1 mutation carriers may soon be available for population
      screening. This article describes preliminary studies investigating health care
      provider and patient perceptions of bilateral prophylactic mastectomy. In
      addition, a number of research questions remain regarding the efficacy and
      utilization of bilateral prophylactic mastectomy as a treatment option for women
      at increased risk of developing breast cancer. These women include those testing
      positive for BRCA1 mutations. In addition, women with a strong family history
      opting against testing for BRCA1 mutations may express interest in surgery.

PMID- 8573453
TI  - Cancer chemoprevention.
AB  - A new direction for cancer prevention and control is chemoprevention, defined as
      the use of specific natural and synthetic chemical agents to reverse or suppress
      carcinogenesis and prevent the development of invasive cancer. The
      chemopreventive approach depends on the ability of certain chemical agents to
      block mutagenesis and control cellular differentiation and proliferation in
      epithelial tissues. Support for the chemopreventive approach is based on the
      biologic concepts of field cancerization and multistep carcinogenesis, as well as
      the clinical efficacy already shown by agents such as retinoids and tamoxifen in
      reversing premalignancy and preventing second primary tumors. Although
      chemoprevention is not yet established as a standard therapy, the results of
      reported trials are very promising and have raised tremendous interest in this
      strategy for cancer prevention. The development of more effective, less toxic
      chemopreventive agents remains a high priority in furthering the use of this
      clinically valuable approach to the prevention and control of cancer.

PMID- 8573452
TI  - Nutritional intervention to prevent hereditary cancer.
AB  - To determine if the effect of nutritional interventions differs by genetic
      susceptibility to cancer, we must have both an effective intervention as well as
      a documented marker of genetic susceptibility. The first large clinical trials to
      test nutritional intervention strategies have recently been reported, and
      apparent efficacy has been observed for selected antioxidants in the primary
      prevention of several cancers, including esophageal, stomach, prostate, and
      colorectal cancers. At the same time, increasing numbers of markers of genetic
      susceptibility are being identified. Although susceptibility markers have not yet
      been evaluated in the context of nutritional interventions in humans, preliminary
      data in animals indicate that calorie restriction reduces spontaneous tumor
      mortality in p53-knockout mice. Linking the results from nutritional
      interventions in humans with markers of genetic susceptibility will allow us to
      better understand gene-environment interactions.

PMID- 8573454
TI  - Hereditary cancers: from discovery to intervention.
AB  - This conference concerned hereditary cancers of the breast, ovary, and colon,
      which are the common, often fatal, cancers with the greatest heritability in
      their causation. Four genes whose mutations impart dominantly heritable
      predisposition to one or more of these cancers have been cloned and one more has
      been mapped. The most molecular details are known for colon cancer. The APC gene
      of familial polyposis coli leads to the accumulation of numerous polyps, but the
      probability of transformation of the latter to cancer is low. This provides the
      opportunity to monitor putative preventive measures with an intermediate end
      point. In hereditary nonpolyposis colon cancer, transformation of the polyp to
      cancer is accelerated by an inherited mutation in either of two DNA mismatch
      repair genes. The discovery of an intermediate end point could be very helpful
      for breast cancer. Testing persons at risk for predisposing mutations depends
      heavily on the availability of promising measures for prevention or treatment.

PMID- 8573456
TI  - Physician responsibility in conducting genetic testing.
AB  - The rapid growth of DNA-based tests raises complex questions about how to
      integrate them efficiently into clinical medicine and about the medicolegal
      consequences of rapidly shifting standards of practice. Standards of practice
      change in response to many factors; the most important are guidelines promulgated
      by professional bodies or published comments by opinion leaders, malpractice
      litigation, and legislation. Recently, human geneticists have successfully shaped
      the clinical use of tests for Huntington's disease and carrier screening for
      cystic fibrosis. Clinical geneticists, oncologists, and others should work
      together now to develop practice standards for the use of new DNA-based
      predictive tests for breast, colon, and other cancers.

PMID- 8573455
TI  - Minority inclusion in clinical trials issues and potential strategies.

PMID- 8573457
TI  - Genetic testing for cancer predisposition: behavioral science issues.
AB  - The discovery of major cancer susceptibility genes is likely to create strong
      pressures for clinical testing from biotechnology companies, insurance carriers,
      the medical community, and the public. However, before genetic testing for cancer
      predisposition is made widely available, we must identify the optimum strategies
      to enhance informed decision making, minimize adverse psychologic consequences,
      and promote adherence to recommended surveillance. This report provides an
      overview of behavioral research in these areas and, on the basis of this
      literature, presents suggestions for developing effective and ethical genetic
      testing protocols.

PMID- 8573458
TI  - Gene tests and counseling for colorectal cancer risk: lessons from familial
      polyposis.
AB  - Familial adenomatous polyposis (FAP) is a well-defined, inherited colorectal
      cancer syndrome due to mutations in the APC gene. Genetic counseling and
      predictive gene tests for FAP will likely be incorporated as a first step in risk
      assessment for this condition. Our experience with predictive gene testing for
      FAP sheds important light on the impact of such tests for families at risk for
      FAP or colorectal cancer. We counseled and tested 47 adults and 36 minors at risk
      for FAP. Gene test results changed the risk of FAP for a given individual from a
      priori 50% to essentially zero or 100%. These individuals and their family
      members were interviewed before and after disclosures of APC gene test results to
      examine issues related to patients' knowledge about FAP, risk perception, reasons
      for seeking gene testing, and anticipated meaning of the results. We found that
      the gene test is imbued with meaning beyond determination of gene status in
      families who choose gene testing. The at-risk patient has preformed, well
      entrenched conceptions of what having FAP or colorectal cancer entails, and
      family relationships and identity may be strongly linked with disease or gene
      status. We have found that genetic testing of minors requires additional
      counseling considerations and effort to ensure their understanding of FAP and the
      gene test. Importantly, their understanding of the clinical and social meaning of
      the gene test result must be elicited. For all patients, the value of counseling
      includes reduction of uncertainty and adjustment of misperceptions. Genetic
      counseling guidelines for this emerging clinical service are presented.

PMID- 8573459
TI  - Psychological counseling strategies for women at risk of breast cancer.
AB  - Women with family histories of breast cancer have a much higher risk of
      developing the disease than women in the general population. In the absence of
      primary prevention for breast cancer, secondary prevention in the form of early
      detection is our best bet against premature morbidity and mortality. This article
      describes the most salient psychological issues for high-risk women as well as
      ways for improving screening behaviors. Based on our work and other studies in
      the literature, we found that there were several key variables related to
      psychological distress and surveillance behaviors. Barriers to screening were a
      major reason why women did not engage in any breast cancer prevention behaviors.
      Cognitive deficits, in terms of lack of knowledge, and breast cancer misbeliefs
      contributed to poor adherence to screening. Most important, anxiety or emotional
      distress not only interfered with adherence to screening but also affected
      quality of life negatively in that many women needed psychological counseling. In
      developing psychological counseling strategies for high-risk women, we focused on
      the treatment outcomes of reducing emotional distress, decreasing perceived
      vulnerability, and improving adherence to screening behaviors. We conducted a
      preliminary study by piloting a group psychoeducational intervention for 6
      consecutive weeks. This intervention was found to significantly reduce perception
      of risk (P < .02) and to increase adherence to screening behaviors (P < .01). If
      proven effective in a randomized controlled trial, this intervention can be
      proposed to other cancer centers and prevention programs for implementation and
      enhancement of the behaviors among high-risk women that will assure early
      detection and decrease breast cancer mortality.

PMID- 8573460
TI  - Women at risk of ovarian cancer.
AB  - This paper evaluates perceived cancer risk and worry about cancer among women
      with genetic risk of ovarian cancer. Women with a first-degree relative with
      ovarian cancer who were participating in screening were compared with a general
      population sample who had been screened the previous year and a group of
      community controls. The results showed that both worry about cancer and perceived
      risk were higher in the screening groups than in the controls. Estimates of
      general-population prevalence were on the optimistic side (only 31% estimating
      that more than one of 10 women would develop cancer in their lifetime) and were
      unrelated to any psychologic factors, genetic risk, or to personal experience of
      cancer, but were related to occupational status. In multivariate analyses,
      perceived personal cancer risk was higher in screening attenders and related to
      (lower) optimism and knowing more people with cancer. Cancer worry was also
      higher in screening attenders and associated with lower optimism and a monitoring
      coping style.

PMID- 8573461
TI  - Genetic testing: employability, insurability, and health reform.
AB  - Presently, 85%-90% of individuals with private health insurance are covered under
      group health insurance, with most covered through employment. Under virtually any
      system of health care reform likely to be enacted in the near future, employers
      will continue to play a major role in the funding of private health care. As
      costs of health care are increasing dramatically, employers and insurance
      carriers are examining alternatives for controlling health care expenditures. Not
      all consumers of health care are equal in their rates of consumption. Tremendous
      savings could be realized by parties responsible for paying for health care if
      the most expensive (or potentially most expensive) health care users could be
      identified and their costs shifted to another payer. Genetic testing could play a
      major role in predictive health screening to identify individuals with the
      potential for developing cancer. This prospect raises three major problems
      regarding employability and insurability. First, individuals could be subject to
      discrimination in employment, with the responsibility for their health coverage
      shifted to the public sector. Second, privacy and confidentiality could be
      compromised through the compilation, storage, and release of non-job-related,
      sensitive medical information. Third, the fear of employment discrimination
      through employer access to medical records generated in the clinical setting
      might discourage at-risk individuals from undergoing medically indicated genetic
      testing. This report reviews these issues and emphasizes that these concerns must
      be addressed in the context of health care reform as well as through the
      interpretation of existing legal proscriptions on employment discrimination.

PMID- 8573462
TI  - Genetic analysis of eight breast-ovarian cancer families with suspected BRCA1
      mutations.
AB  - BRCA1 is a breast cancer-related tumor suppressor gene located on human
      chromosome 17q21. Inherited mutations in BRCA1 are thought to be responsible for
      approximately half of all inherited breast cancer and to confer increased risk
      for ovarian, colon, or prostate cancer. Studies of affected families and
      population-based studies have provided some information on the prevalence of
      BRCA1 mutations in Caucasian U.S. and European populations as well as on the
      penetrance of these mutations. We review the available data on the epidemiology
      of breast cancer with specific reference to BRCA1. In addition, we describe the
      genetic analysis of one large family with multiple affected individuals now known
      to harbor a BRCA1 germline mutation but initially identified by genetic linkage
      analysis. This family is presented as a model of the challenges that can be
      encountered in genetic analysis of familial forms of cancer. To this end, we
      compare the outcome of analysis before and after the identification of a mutation
      that predisposes family members to early-onset breast and ovarian cancers. We
      describe seven additional families with evidence of linkage between breast cancer
      and genetic markers in the BRCA1 region. Each of these families generated a 2
      point LOD (i.e., logarithm of the odds) score greater than 1.18 for at least one
      polymorphic marker flanking BRCA1. These families have formed the basis of our
      efforts to characterize BRCA1 mutations. First-pass mutation analysis using the
      single-strand conformation polymorphism approach failed to identify any mutations
      in the seven families. We consider the possible reasons for the apparent low
      mutation-detection efficiency.

PMID- 8573463
TI  - Defining, identifying, and studying high-risk families: developing cohorts for
      epidemiologic study.
AB  - Many issues arise in planning epidemiologic studies of individuals at high risk
      for developing hereditary cancers. The most important are (a) determination of
      the information that can best be studied in epidemiologic settings; (b) selection
      of proper study designs; (c) acknowledgment of the ethical, psychosocial, and
      legal issues that will arise in these studies; and (d) anticipation of the
      logistical issues involved in large, multicenter studies. The breakout session
      "Developing Cohorts for Epidemiologic Study: Defining and Identifying High-Risk
      Families" examined these issues, and the results of that session are summarized
      here. There was general consensus that little information exists regarding the
      prevalence of genetic mutations that predispose individuals to increased cancer
      risk, the risks conferred by specific mutations and by gene-environment
      interactions, and the efficacy of potential interventions. Adequately controlled
      observational and randomized studies provide the best mechanism for obtaining
      this information, despite the considerable ethical and strategic difficulties
      that will arise in the planning and conduct of such studies.

PMID- 8573464
TI  - Scale-up technology: moving predictive tests for inherited breast, ovarian, and
      colon cancers from the bench to the bedside and beyond.

PMID- 8573465
TI  - Developing strategies for intervention and prevention in hereditary breast
      cancer.
AB  - Prophylactic mastectomy, intensified breast cancer screening, and the use of
      chemopreventive agents have all been recommended to reduce breast cancer risk in
      women with a family history of breast cancer. Yet, little is currently known
      about the efficacy of these approaches in reducing breast cancer mortality. The
      recent identification of BRCA1 and the localization of BRCA2 lend urgency to the
      need to assess breast cancer intervention and prevention strategies for women
      likely to carry germline mutations at these loci. At present, families with a
      history consistent with a BRCA1 or BRCA2 mutation should be tested within the
      confines of a research protocol and encouraged to participate in intervention and
      prevention trials. Both retrospective studies and prospective clinical trials are
      critically needed. While randomized clinical trials would be the optimal
      mechanism to assess the relative efficacy of these potential interventions, no
      consensus was obtained as to whether such a trial would be feasible because of
      strong patient preference for intervention type. It is likely that optimal
      intervention and prevention strategies will consist of a combined approach to
      risk reduction. Participants must be appropriately informed of the potential
      risks as well as the potential benefits of such testing. The potential risks of
      testing for genetic susceptibility include not only potential psychosocial harm
      that may result from learning one's carrier status, but also the potential for
      altered family relationships and insurance and job discrimination. Participants
      and their family members must be counseled concerning the implication of their
      test results.

PMID- 8573466
TI  - Visualization of individual reovirus particles by low-temperature, high
      resolution scanning electron microscopy.
AB  - We used low-temperature, high-resolution scanning electron microscopy (cryo
      HRSEM) to visualize surface structures on individual reovirus particles. Both
      intact virions and two forms of subvirion particles--infectious subvirion
      particles and cores--were examined, and despite some distortion of particles
      during specimen preparation and viewing in the microscope, the images obtained by
      cryo-HRSEM exhibited a level of interpretable detail not routinely achieved by
      other methods without image averaging. Cryo-HRSEM images of discrete reovirus
      particles were used to characterize and confirm features of the outer protein
      capsid of this virus by comparison with image reconstructions previously derived
      from cryotransmission electron microscopy. Distinct surface features attributable
      to each of the four outer-capsid proteins were identified. In addition, cryo
      HRSEM images confirmed that significant changes occur on the surfaces of
      individual reovirus particles during disassembly and entry of cells and that the
      reovirus outer capsid is organized as a left-handed T = 13 icosahedron. Several
      unique capabilities and potential uses suggest that cryo-HRSEM has a place
      alongside other, more established methods for molecular characterizations of
      virus particles.

PMID- 8573467
TI  - Packing of alpha-helical coiled-coil myosin rods in vertebrate muscle thick
      filaments.
AB  - Muscle myosin filament backbones are aggregates of long coiled-coil alpha-helical
      myosin rods, with the myosin heads arranged approximately helically on the
      filament surface, but the details of the rod packing are not known. Computed
      Fourier transforms of plausible molecular packing models for the vertebrate
      striated muscle myosin filament have been compared with observed high-angle X-ray
      diffraction patterns from plaice fin muscle. Models considered include those in
      which the coiled-coil rod parts of myosin are packed into various kinds of
      subfilaments or into a curved molecular crystalline layer. A general conclusion
      is that if the myosin rods are tilted by less than about 1 degree or more than
      about 3 degrees from the filament long axis, very poor agreement is obtained
      between the computed and observed high-angle diffraction patterns. Qualitative
      comparison of calculated Fourier transforms, taken together with electron
      micrograph information, shows that the curved molecular crystal model and a model
      with hexagonally close-packed 4-nm subfilaments appear to explain the whole set
      of observations more satisfactorily than the alternatives. It is argued on other
      grounds that of these two possibilities the curved molecular crystal model is the
      more plausible.

PMID- 8573468
TI  - Three-dimensional reconstruction of thick filaments from rapidly frozen, freeze
      substituted tarantula muscle.
AB  - We have applied three-dimensional helical reconstruction techniques to images of
      myosin filaments of tarantula leg muscle obtained from rapidly frozen, freeze
      substituted specimens. Computed Fourier transforms of filaments selected from
      longitudinal sections show up to six layer lines indexing on the 43.5-nm helical
      repeat of myosin crossbridges. The three-dimensional reconstruction, performed
      after separation of overlapped Bessel functions, shows four continuous strands of
      density on the surface of the filament, modulated by density at 14.5-nm
      intervals, corresponding to the myosin heads aligned approximately along the
      helical strands. In transverse viw, the reconstruction shows four projections and
      is similar in profile to myosin filaments seen in thin transverse sections of
      rapidly frozen muscle. The reconstruction is similar to that of negatively
      stained, isolated tarantula filaments except that in the latter there is an
      additional modulation of the helix density, which better resolves the two heads
      of each myosin crossbridge. Thus, the general arrangement of the myosin heads in
      the freeze-substituted specimens is preserved, although finer details of
      structure such as individual myosin heads are lost.

PMID- 8573469
TI  - Electron microscopy of Bacillus subtilis GroESL chaperonin and interaction with
      the bacteriophage phi 29 head-tail connector.
AB  - The Bacillus subtilis GroESL chaperonin was isolated by sucrose density gradient
      centrifugation and the constituent GroES and GroEL moieties were purified by
      electrophoresis in agarose. Electron microscopic images of negatively stained
      GroEL and GroES oligomers and GroESL complexes were averaged using a reference
      free alignment method. The GroEL and GroES particles had the sevenfold symmetry
      characteristic of their Escherichia coli counterparts. GroESL complexes,
      reconstituted efficiently in vitro from GroEL and GroES in the absence of added
      ADP or ATP, had the characteristic bullet- and football-like shapes in side view.
      Purified bacteriophage phi 29 head-tail connectors having a mass in excess of 0.4
      MDa were shown to bind to GroESL at the end opposite to the GroES. The same
      GroESL-connector complexes were isolated from phage-infected cells in which
      capsid assembly was blocked, and thus the complex may have functional
      significance in phi 29 morphogenesis.

PMID- 8573470
TI  - Identification of the tailspike protein from the Salmonella newington phage
      epsilon 34 and partial characterization of its phage-associated properties.
AB  - The lipopolysaccharide (LPS) of the Salmonella cell surface serves as the
      receptor for a very large number of bacterial viruses. The tailspike protein from
      these viruses recognizes the LPS as its initial receptor. It is proposed that the
      study of the P22 and epsilon 34 tailspike proteins could serve as a model for the
      study of the interaction of proteins with LPS. Toward this end, the tailspike
      protein of the epsilon 34 phage has been identified. The data suggest
      similarities between the epsilon 34 tailspike protein and the P22 tailspike
      protein. Some properties related to the interaction of the phage tailspike with
      its receptor are reported.

PMID- 8573471
TI  - Improved procedures for electron microscopic visualization of the cytoskeleton of
      cultured cells.
AB  - We have developed an improved electron microscopic procedure appropriate for
      correlative light and electron microscopy of the cytoskeleton. The procedure is
      based on detergent extraction, chemical fixation, critical point drying, and
      platinum/carbon coating of cultured cells and the improvements consist of
      modifications which are minor individually but collectively of substantial
      impact. They are: inclusion of polyethylene glycol into the extraction medium;
      cell lysis at room temperature; fixation by sequential application of
      glutaraldehyde, tannic acid, and uranyl acetate; horizontal position of specimens
      during dehydration and drying; and uranyl acetate treatment during dehydration.
      As a result, we have obtained a greatly improved quality of electron microscopic
      images together with a high consistency of results. Long and straight actin
      filaments were clearly seen in stress fibers and newly formed lamellipodia. Their
      polarity was distinctly revealed by decoration with myosin subfragment 1.
      Depletion of actin from cytoskeletons by gelsolin treatment allowed for better
      visualization of myosin, intermediate filaments, and microtubules. Intermediate
      filaments exposed by this treatment exhibited numerous side projections in a
      hitherto unreported millipede-like appearance. The suggested procedure was
      compatible with immunogold labeling as demonstrated with an antibody to tubulin.
      Correlative light and electron microscopy of cells microinjected with a
      fluorescent derivative of myosin II was reliable and efficient, producing a close
      resemblance between the two kinds of images.

PMID- 8573472
TI  - Distribution and ultrastructure of plectin arrays in subclones of rat glioma C6
      cells differing in intermediate filament protein (vimentin) expression.
AB  - Histochemical and biochemical studies suggest that the functions of the
      intermediate filament (IF) binding protein plectin comprise the physical linkage
      of IFs to each other and to other cytoskeletal elements, and their anchorage at
      membrane-attached junctional complexes. To further evaluate this hypothesis the
      expression, cellular distribution, and ultrastructure of plectin arrays were
      studied in rat glioma C6 cell subclones differing in IF protein (vimentin)
      expression. Here we show that plectin is expressed in a vimentin-negative C6 cell
      subclone (C6-D10) at levels similar to those of the vimentin-positive control
      subclone C6-D8. However, the amount of cytoskeleton-associated plectin found
      after extraction of cells with Triton X-100 or Triton X-100/high salt was
      significantly reduced in IF-negative compared to IF-positive cells. Using
      immunofluorescence microscopy, plectin structures were detected throughout the
      cytoplasm of IF-deficient cells. Unlike in IF-containing cells, where plectin
      colocalized largely with the vimentin network, in the IF-negative subclone the
      protein was mainly associated with polymeric actin structures. The release of
      plectin from IF-deficient cytoskeletons upon treatment with heavy meromyosin
      argued for specificity of the plectin microfilament interaction. Whole mount
      electron microscopy in conjunction with immunogold labeling of cytoskeletons
      revealed that in both IF-positive and IF-negative cells, plectin label
      specifically associated with thin (3-nm) filamentous structures that were clearly
      distinct from the major cytoskeletal filament systems. In IF-containing cells
      these filaments were found to link IFs to actin filaments and to connect vimentin
      filaments to each other. In IF-deficient cells, filamentous plectin structures
      were found to form dense cytoplasmic networks together with actin filaments and
      actin filament bundles. These data support the hypothesis that filamentous
      plectin arrays play an important role in the structural organization and
      mechanical integration of the cytoskeleton, in particular IFs and microfilaments.

PMID- 8573474
TI  - Crystallization of rat liver macrophage migration inhibitory factor for MAD
      analysis.
AB  - The recombinant macrophage migration inhibitory factor (MIF) of a rat liver was
      crystallized using the hanging-drop vapor diffusion method. We also crystallized
      a selenomethionyl rat MIF under similar conditions for X-ray structure analysis
      using the multiwavelength anomalous diffraction method. Furthermore, two kinds of
      selenomethionyl rat MIF mutants, in which one or two of three methionine residues
      were replaced by alanine [(Met101Ala), (Met2Ala and Met101Ala)], were constructed
      and crystallized. These crystals belong to two different forms of the hexagonal
      space group P6(3). The first form has cell dimensions of a = b = 95.7 A and c =
      87.9 A and contains two dimers in an asymmetric unit, while the second form,
      whose cell dimensions are a = b = 61.8 A and c = 53.4 A, contains only one
      subunit in an asymmetric unit. Preliminary X-ray examination shows that these
      crystals are suitable for high-resolution structure analysis.

PMID- 8573473
TI  - The pathway of Golgi cluster formation in okadaic acid-treated cells.
AB  - Using stereology and immunoelectron microscopy we examined the pathway of Golgi
      cluster formation during treatment with the phosphatase inhibitor okadaic acid.
      During the first hour the Golgi stack of suspension HeLa cells lost 90% of its
      membrane without appreciable reduction in the number of cisternae. During this
      time clusters of tubules and vesicles (Golgi clusters) appeared and these
      contained only a fraction of the Golgi membrane present in untreated cells.
      Despite the overall reduction in membrane the total amount of immunolabeling for
      galactosyltransferase over the Golgi clusters of a typical cell was maintained,
      indicating that galactosyltransferase had been retained in Golgi membranes. The
      observation that, after 40 min okadaic acid treatment, labeling density for
      galactosyltransferase within trans Golgi cisternae increased 1.6-fold (n = 3, CE
      10%) suggests that membrane loss from trans cisternae was selective. Careful
      evaluation of immunolabeled clusters showed that most of the
      galactosyltransferase labeling was located over complex tubular profiles and not
      vesicular profiles. Tubular structures were also observed during disassembly and
      these were found both connected to disassembling cisternae and within forming
      Golgi clusters, indicating that they were intermediates in cluster formation. We
      also investigated the role of vesicular transport in cluster formation. During
      disassembly we found no accumulation of COP-coated buds and vesicles over Golgi
      membrane. However, aluminium fluoride, previously found to arrest transport in
      the Golgi stack, completely inhibited membrane depletion and stack disassembly.
      Taken together, our results indicate that during Golgi cluster formation,
      membrane leaves the Golgi but galactosyltransferase is retained within a tubular
      reticulum which is a direct descendant of trans-Golgi cisternae. Membrane
      depletion may require ongoing vesicular transport and we postulate that it arises
      because of an imbalance in membrane traffic into and out of the Golgi apparatus.

PMID- 8573475
TI  - Crystallization and preliminary X-ray analysis of Borrelia burgdorferi outer
      surface protein A (OspA) complexed with a murine monoclonal antibody Fab
      fragment.
AB  - The Borrelia burgdorferi outer surface lipoprotein OspA is a current focus for
      vaccine development to prevent Lyme disease infection. A soluble, recombinant
      form of the protein lacking the amino-terminal lipid membrane anchor was
      cocrystallized with the Fab fragment of an agglutinating mouse monoclonal
      antibody. The crystals belong to space group P2(1)2(1)2(1), with a = 90.0 A, b =
      91.9 A, and c = 102.9 A and they were found to diffract to a maximum resolution
      of 2.8 A using synchrotron radiation.

PMID- 8573476
TI  - Role of chemotherapy dose intensification in the treatment of advanced ovarian
      cancer.
AB  - Cisplatin (Platinol) has been the most active agent against ovarian cancer. The
      question of a relationship between platinum dose and response remains unresolved.
      Eight prospective, randomized studies have examined the role of platinum dose
      intensity in the front-line management of newly diagnosed ovarian cancer. In none
      of these studies did the dose intensities achieved exceed twice that of a
      standard regimen. Additionally, none of these studies addressed the role of truly
      high-dose therapy requiring hematologic support. Recent evidence supports the
      idea that more substantial intensification of platinum drug delivery may be
      achieved by intraperitoneal administration. Similarly, very-high-dose platinum
      based chemotherapy with autologous bone marrow transplantation has been shown to
      produce high levels of response in patients refractory to conventional-dose
      platinum. However, these high response rates have been achieved at the cost of
      considerable morbidity and generally have been of short duration. The use of
      peripheral blood progenitor cells may now allow us to evaluate further the role
      of platinum dose intensification and is currently under investigation.

PMID- 8573478
TI  - Protecting against stomatitis.

PMID- 8573477
TI  - Clinical trials referral resource. Tumor vaccine clinical trials.

PMID- 8573479
TI  - BCG immunotherapy for transitional-cell carcinoma in situ of the bladder.
AB  - Prior to the advent of BCG immunotherapy, bladder carcinoma in situ often
      progressed to muscle invasion. Intravesical chemotherapy completely eradicates
      the disease in 50% of patients, but fewer than 20% remain disease free after 5
      years. Complete responses have been reported in 70% or more of BCG treated
      patients, nearly two-thirds of which are durable. Controversy over the optimal
      induction and maintenance regimens for BCG immunotherapy remain, but SWOG
      investigators have demonstrated that complete response rates can be increased
      from the expected 73% to 87% with just three additional BCG instillations given
      at 3 months. In complete responders, maintenance BCG using three weekly
      treatments at 6-month intervals improves long-term complete response rates from
      65% to nearly 90%. Caution must be exercised to avoid serious side effects.

PMID- 8573480
TI  - Endoscopic diagnosis and management of gastrointestinal malignancy.
AB  - The endoscopic diagnosis, staging, and therapy of gastrointestinal (GI)
      malignancies has advanced rapidly and dramatically over the past 15 years. Video
      endoscopy has generally replaced fiberoptic endoscopy, and the digitally based
      fidelity, sharper resolution, and improved magnification of the video-endoscopic
      image offers a potentially better approach for the evaluation of mucosal
      abnormalities. Endoscopic diagnosis of GI malignancies has been enhanced by the
      recent development of selective vital staining techniques of mucosal
      abnormalities and more sensitive and aggressive biopsy techniques. The recent
      dissemination of endoscopic ultrasound has propelled preoperative TNM staging
      into a new realm of accuracy and has afforded additional potential for directed
      biopsy techniques. Therapy of GI malignancies has advanced through the
      development of thermal and nonthermal laser technology, tumor probes, expandable
      stents, and endoscopic resection techniques.

PMID- 8573481
TI  - Management of congenital vascular lesions of the head and neck.
AB  - Congenital vascular lesions are often misdiagnosed and, for the most part, left
      untreated. The absence of a uniformly accepted classification of these lesions
      and confusion over their natural history are partly responsible. A new
      classification of these lesions recognizes two distinct groups of lesions,
      hemangiomas and vascular malformations. Hemangiomas are usually not present at
      birth, proliferate during the first year of life, and then involute. In contrast,
      vascular malformations are always present at birth, never proliferate, and never
      involute. Knowledge of this classification system will facilitate the diagnosis
      of these lesions and lead to appropriate, individualized treatment.

PMID- 8573482
TI  - Molecular phylogeny of the genus Frankia and related genera and emendation of the
      family Frankiaceae.
AB  - The members of the actinomycete genus Frankia are nitrogen-fixing symbionts of
      may species of woody dicotyledonous plants belonging to eight families. Several
      strains isolated from diverse actinorhizal plants growing in different
      geographical areas were used in this study. The phylogenetic relationships of
      these organisms and uncharacterized microsymbionts that are recalcitrant to
      isolation in pure culture were determined by comparing complete 16S ribosomal DNA
      sequences. The resulting phylogenetic tree revealed that there was greater
      diversity among the Alnus-infective strains than among the strains that infect
      other host plants. The four main subdivisions of the genus Frankia revealed by
      this phylogenetic analysis are (i) a very large group comprising Frankia alni and
      related organisms (including Alnus rugosa Sp+ microsymbionts that are seldom
      isolated in pure culture), to which Casuarina-infective strains, a Myrica nagi
      microsymbiont, and other effective Alnus-infective strains are related; (ii)
      unisolated microsymbionts of Dryas, Coriaria, and Datisca species; (iii)
      Elaeagnus-infective strains; and (iv) "atypical" strains (a group which includes
      an Alnus-infective, non-nitrogen-fixing strain). Taxa that are related to this
      well-defined, coherent Frankia cluster are the genera Geodermatophilus,
      "Blastococcus," Sporichthya, Acidothermus, and Actinoplanes. However, the two
      genera whose members have multilocular sporangia (the genera Frankia and
      Geodermatophilus) did not form a coherent group. For this reason, we propose that
      the family Frankiaceae should be emended so that the genera Geodermatophilus and
      "Blastococcus" are excluded and only the genus Frankia is retained.

PMID- 8573483
TI  - Analysis of the phylogenetic relationships of strains of Burkholderia
      solanacearum, Pseudomonas syzygii, and the blood disease bacterium of banana
      based on 16S rRNA gene sequences.
AB  - We determined nearly complete 16S rRNA gene sequences for 19 isolates of
      Burkholderia solanacearum, three isolates of the blood disease bacterium of
      bananas, and two isolates of Pseudomonas syzygii, the cause of Sumatra disease of
      cloves. The dendrogram produced by comparing all of these sequences revealed that
      there were two divisions, which corresponded to the results obtained previously
      in a restriction fragment length polymorphism analysis (D. Cook, E. Barlow, and
      L. Sequeira, Mol. Plant Microbe Interact. 2:113-121, 1989) and a total 16S
      ribosomal DNA (rDNA) sequence analysis of four isolates representing four biovars
      of B. solanacearum (X. Li, M. Dorsch, T. Del Dot, L. I. Sly, E. Stackebrandt, and
      A. C. Hayward, J. Appl. Bacteriol. 74:324-329, 1993). Division 1 comprised
      biovars 3, 4, and 5 and an aberrant biovar 2 isolate (strain ACH0732), and
      division 2 included biovars 1, 2, and N2, the blood disease bacterium, and P.
      syzygii. Specific nucleotides at positions 458 to 460 (UUC) and 474 (A)
      characterized division 2, whereas in division 1 the nucleotides at these
      positions were ACU and U, respectively. However, strain ACH0732 had a U at
      position 458, as did division 2 isolates, and G instead of U at position 474.
      Division 2 consisted of two subdivisions; one subdivision contained two B.
      solanacearum isolates that originated from Indonesia, P. syzygii strains, and
      blood disease bacterium strains, and the other subdivision contained all of the
      other division 2 isolates. Within division 1, the level of 16S rDNA sequence
      similarity ranged from 99.8 to 100%, and within division 2, the levels of 16S
      rDNA sequence similarity ranged from 99.1 to 100%. The division 1 isolates
      exhibited an average level of 16S rDNA sequence similarity to division 2 isolates
      of 99.3% (range, 99.1 to 99.5%). The occurrence of consistent polymorphisms in
      the 16S rDNA sequences of B. solanacearum strains, in particular unique 16S rDNA
      sequence differences in aberrant biovar 2 isolate ACH0732, and the occurrence of
      the Indonesian subdivision of division 2 suggest that this group is a rapidly
      evolving (tachytelic) group.

PMID- 8573484
TI  - 16S rRNA and 16S to 23S internal transcribed spacer sequence analyses reveal
      inter- and intraspecific Bifidobacterium phylogeny.
AB  - In the last few years many attempts have been made to differentiate more than 20
      Bifidobacterium species. It has been recognized that identification of
      bifidobacterial species is problematic because of phenetic and genetic
      heterogeneities. In order to contribute to our understanding of Bifidobacterium
      taxonomy, we studied Bifidobacterium phylogeny by performing both 16S rRNA and
      16S to 23S (16S-23S) internally transcribed spacer (ITS) sequence analyses. In
      this study, we determined 16S rRNA sequences of five Bifidobacterium strains
      representing four species, and compared them with the sequences available in the
      GenBank database, and used them to construct a distance tree and for a bootstrap
      analysis. Moreover, we determined the ITS sequences of 29 bifidobacterial strains
      representing 18 species and compared these sequences with each other. We
      constructed a phylogenetic tree based on these sequence data and compared this
      tree with the tree based on 16S rRNA sequence data. We found that the two trees
      were similar topologically, suggesting that the two types of molecules provided
      the same kind of phylogenetic information. However, while 16S rRNA sequences are
      a good tool to infer interspecific links, the 16S-23S rDNA spacer data allowed us
      to determine intraspecific relationships. Each of the strains was characterized
      by its own ITS sequence; hence, 16S-23S rRNA sequences are a good tool for strain
      identification. Moreover, a comparison of the ITS sequences allowed us to
      estimate that the maximum level of ITS divergence between strains belonging to
      the same species was 13%. Our data allowed us to confirm the validity of most of
      the Bifidobacterium species which we studied and to identify some classification
      errors. Finally, our results showed that Bifidobacterium strains have no tRNA
      genes in the 16S-23S spacer region.

PMID- 8573485
TI  - Serological and molecular characterization of Mesoplasma seiffertii strains
      isolated from hematophagous dipterans in France.
AB  - Three strains of nonhelical mollicutes previously isolated in France from two
      different mosquitoes and one tabanid fly were designated strains Ar 2328
      (isolated from Aedes detritus), Ar 2392 (isolated from Aedes caspius), and CP 13
      (isolated from Chrysops pictus). All of these strains exhibited properties of the
      genus Mesoplasma, a recently described genus of non-sterol-requiring mollicutes
      isolated from plants and insects. The results of metabolism inhibition and growth
      inhibition tests revealed that these strains and Mesoplasma entomophilum TAC or
      Mesoplasma florum L1 were not serologically related, but all three dipteran
      strains reacted strongly with Mesoplasma seiffertii F7T (T = type strain)
      antibodies. Using metabolism inhibition and growth inhibition tests, we found
      that the dipteran strains were related to each other and to strain F7T but were
      not identical. We also found that they were able to multiply and persist in the
      central nervous systems of suckling mice inoculated intracerebrally, a property
      that makes their use as biological control agents for pest dipterans inadvisable.
      Scanning electron microscopy revealed marked differences in the morphologies of
      the colonies of the different strains on SP4 solid medium. The levels of DNA-DNA
      homology for strains Ar 2328, Ar 2392, CP 13, and F7T were more than 70%,
      indicating that these strains are closely related members of the same species, M.
      seiffertii. In addition, one-dimensional sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis revealed that each strain produced about 40 protein bands.
      This technique also revealed differences between strains. Using the coefficient
      of Smeath-Jacquart, we constructed a dendrogram that allowed us to estimate of
      the levels of relatedness of these four strains. The results which we obtained
      were confirmed by two-dimensional protein electrophoresis results.

PMID- 8573486
TI  - "Candidatus comitans," a bacterium living in coculture with Chondromyces crocatus
      (myxobacteria).
AB  - We describe the phylogenetic position and some taxonomically relevant
      characteristics of a small pleomorphic gram-negative bacterium that was
      cocultured with some strains of the myxobacterium Chondromyces crocatus that were
      isolated from the same geographic and ecological habitat. A 16S ribosomal DNA
      analysis revealed that the companion was a member of the "Cytophaga
      Flavobacterium-Bacteroides" complex and was most closely related to members of
      the genus Sphingobacterium. The results of a fatty acid analysis, an isoprenoid
      composition analysis, and a DNA G+C content analysis and the presence of
      sphingolipids confirmed that this bacterium is affiliated with the genus
      Sphingobacterium. As the companion bacterium survived for only a few generations
      on solid media and could not be maintained in pure culture, we assign to this
      novel taxon that lives in close association with the myxobacterium C. crocatus
      Candidatus status as "Candidatus comitans."

PMID- 8573487
TI  - Characterization of a new obligately anaerobic thermophile, Thermoanaerobacter
      wiegelii sp. nov.
AB  - An obligately anaerobic, extremely thermophilic Thermoanaerobacter species was
      isolated from a freshwater pool formed from a geothermally heated (56 to 69
      degrees C) water outlet in Government Gardens, Rotorua, New Zealand. This
      organism was a spore-forming, gram-negative, rod-shaped bacterium. Strain Rt8.B1T
      (= DSM 10319T) (T = type strain) fermented a wide variety of mono-, di-, and
      polysaccharides and produced ethanol, acetate, lactate, propionate, and hydrogen.
      Sugar alcohols were also fermented, but organic acids and amino acids were not
      utilized. On the basis of its morphological characteristics, DNA G + C content,
      obligately anaerobic, thermophilic, polysaccharolytic nature, and levels of 16S
      rRNA sequence homology, we propose that strain Rt8.B1T should be classified in
      the genus Thermoanaerobacter as a new species, Thermoanaerobacter wiegelii.

PMID- 8573488
TI  - Characterization of the SF agent, an Ehrlichia sp. isolated from the fluke
      Stellantchasmus falcatus, by 16S rRNA base sequence, serological, and
      morphological analyses.
AB  - The organism designated the SF agent was originally isolated in Japan in 1962
      from Stellantchasmus falcatus metacercaria parasitic on gray mullet fish. The SF
      agent resembles members of the genus Ehrlichia morphologically and exhibits weak
      antigenic cross-reactivity with Ehrlichia sennetsu. This organism causes mild
      clinical signs in dogs, but severe splenomegaly and lymphadenopathy in mice. This
      suggests that the SF agent may be similar to either Neorickettsia helminthoeca,
      an intracellular parasite of a fluke and the cause of salmon poisoning disease in
      dogs, or E. sennetsu, the causative agent of human sennetsu ehrlichiosis in Japan
      and Malaysia. In order to determine the phylogenetic relationship between the SF
      agent and other ehrlichial species, the 16S rRNA gene was amplified by the PCR
      and sequenced. The SF agent sequence was most closely related to the sequences of
      Ehrlichia risticii (level of sequence similarity, 99.1%), the causative agent of
      Potomac horse fever, and E. sennetsu (level of sequence similarity, 98.7%). The
      next most similar sequence was that of N. helminthoeca, but the level of sequence
      similarity was only 93.7%. E. sennetsu, E. risticii, the SF agent, and N.
      helminthoeca formed a distinct cluster that was separated from all other
      ehrlichial species. As determined by immunofluorescence labeling, antiserum
      against the SF agent cross-reacted strongly with E. sennetsu, E. risticii, and N.
      helminthoeca. When three genetically distinct ehrlichial isolates obtained from
      horses with Potomac horse fever were compared with the SF agent, we found that
      the SF agent was most closely related to Ohio isolate 081, followed by IllinoisT
      (T = type strain) and a Kentucky isolate. We observed strong antigenic cross
      reactivities and similarities in Western blot (immunoblot) reaction profiles when
      we compared the SF agent, E. risticii, and E. sennetsu; however, weaker antigenic
      cross-reactivity was observed when the SF agent and N. helminthoeca were
      compared. Our results indicate that the SF agent is antigenically more closely
      related to E. risticii and E. sennetsu than to N. helminthoeca. The biological
      and antigenic characteristics and the 16S rRNA sequence data suggest that the SF
      agent is a new species that belongs to the genus Ehrlichia.

PMID- 8573489
TI  - Transfer of "Pseudomonas riboflavina" (Foster 1944), a gram-negative, motile rod
      with long-chain 3-hydroxy fatty acids, to Devosia riboflavina gen. nov., sp.
      nov., nom. rev.
AB  - The taxonomic position of "Pseudomonas riboflavina" was studied by 16S rRNA gene
      sequencing and chemotaxonomic methods. This organism is a gram-negative, strictly
      aerobic rod and has a DNA guanine-plus-cytosine content of 61.4 mol%; the major
      isoprenoid quinone is ubiquinone 10, and the unusual cellular fatty acids 3
      hydroxytetracosenoic acid (3-OH 24:1) and 3-hydroxyhexacosenoic acid (3-OH 26:1)
      are the major 3-hydroxy cellular fatty acids. A phylogenetic analysis based on
      16S rRNA sequences revealed that "P. riboflavina" IFO 13584T (T = type strain)
      occupies an independent position in the alpha subclass of the Proteobacteria. On
      the basis of our data, we propose that "P. riboflavina" IFO 13584T should be
      transferred to the genus Devosia gen. nov. as Devosia riboflavina sp. nov., nom.
      rev.

PMID- 8573490
TI  - Culture and characteristics of Helicobacter bizzozeronii, a new canine gastric
      Helicobacter sp.
AB  - Organisms whose cells were large, tight spirals were isolated from gastric
      biopsies of dogs. Touch cytology samples from all of the dogs contained large
      spiral organisms. Characteristics of 10 strains are described. These organisms
      were 5 to 10 microns long by 0.3 microns wide, and each cell had 10 to 20
      sheathed flagella at both ends of the cell. The cells did not have periplasmic
      fibrils. These organisms were microaerophilic and grew at 37 and 42 degrees C but
      not at 25 degrees C on brain heart infusion agar containing blood. They did not
      grow on brucella blood agar. They were catalase and oxidase positive, hydrolyzed
      urea but not hippurate, reduced nitrate, and were resistant to nalidixic acid but
      susceptible to cephalothin and metronidazole. In contrast to Helicobacter felis,
      they hydrolyzed indoxyl acetate. The sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis protein profiles of all of the strains were similar, and the
      protein patterns of these organisms differed from those of other Helicobacter
      spp. Dot blot DNA-DNA hybridization experiments revealed that the new strains
      were closely related to each other but clearly different from H. felis,
      Helicobacter pylori, Helicobacter mustelae, and Campylobacter jejuni. The name
      Helicobacter bizzozeronii sp. nov. is proposed for these organisms. Our results
      suggest that other "uncultured" gastric helicobacters may be cultured if optimal
      culture conditions are found.

PMID- 8573491
TI  - Analysis of the genetic polymorphism of Borrelia burgdorferi sensu lato by
      multilocus enzyme electrophoresis.
AB  - In recent years, Borrelia burgdorferi sensu lato has been subdivided into three
      species, Borrelia burgdorferi sensu stricto, Borrelia garinii, and Borrelia
      afzelii, and a new species restricted to Japan, Borrelia japonica, has been
      isolated from Ixodes ovatus. In addition, members of several new genomic groups
      have been found in America and in Europe, suggesting that there are additional
      genospecies. In order to study the diversity of B. burgdorferi sensu lato, we
      analyzed 54 isolates, cultured from humans and from different tick species and
      obtained from diverse geographic areas, including Europe, the United States,
      Japan, and the People's Republic of China. In order to investigate the genetic
      relationship between microorganisms that are transmitted by soft ticks and
      microorganisms that cause Lyme disease, we also included three strains of
      relapsing fever spirochetes. The method which we used was multilocus enzyme
      electrophoresis; 12 genetic loci were characterized on the basis of the
      electrophoretic mobilities of their products, and 50 distinct allele profiles
      (electrophoretic types) were distinguished. The mean genetic diversity per locus
      was 0.747. a cluster analysis of a matrix of genetic distances for pairs of
      electrophoretic types revealed 11 divisions that were separated at genetic
      distances greater than 0.65. Five of these divisions corresponded to B.
      burgdorferi sensu stricto, B. garinii, B. afzelii, B. japonica, and the newly
      proposed species "Borrelia andersonii." Our results also confirmed that there are
      two additional genomic groups in Europe and at least one additional group in the
      United States. The relapsing fever spirochetes were were not clearly separated
      from the spirochetes associated with Lyme disease. In conclusion, we believe that
      the previously proposed subdivision of B. burgdorferi sensu lato into only four
      species should be reconsidered.

PMID- 8573492
TI  - Phylogeny of the Sphaerotilus-Leptothrix group inferred from morphological
      comparisons, genomic fingerprinting, and 16S ribosomal DNA sequence analyses.
AB  - Phase-contrast light microscopy revealed that only one of eight cultivated
      strains belonging to the Sphaerotilus-Leptothrix group of sheathed bacteria
      actually produced a sheath in standard growth media. Two Sphaerotilus natans
      strains produced branched cells, but other morphological characteristics that
      were used to identify these bacteria were consistent with previously published
      descriptions. Genomic fingerprints, which were obtained by performing PCR
      amplification with primers corresponding to enterobacterial repetitive intergenic
      consensus sequences, were useful for distinguishing between the genera
      Sphaerotilus and Leptothrix, as well as among individual strains. The complete
      16S ribosomal DNA (rDNA) sequences of two strains of "Leptothrix discophora"
      (strains SP-6 and SS-1) were determined. In addition, partial sequences
      (approximately 300 nucleotides) of one strain of Leptothrix cholodnii (strain LMG
      7171), an unidentified Leptothrix strain (strain NC-1), and four strains of
      Sphaerotilus natans (strains ATCC 13338T [T = type strain], ATCC 15291, ATCC
      29329, and ATCC 29330) were determined. We found that two of the S. natans
      strains (ATCC 15291 and ATCC 13338T), which differed in morphology and in their
      genomic fingerprints, had identical sequences in the 300-nucleotide region
      sequenced. Both parsimony and distance matrix methods were used to infer the
      evolutionary relationships of the eight strains in a comparison of the 16S rDNA
      sequences of these organisms with 16S rDNA sequences obtained from ribosomal
      sequence databases. All of the strains clustered in the Rubrivivax subdivision of
      the beta subclass of the Proteobacteria, which confirmed previously published
      conclusions concerning selected individual strains. Additional analyses revealed
      that all of the S. natans strains clustered in one closely related group, while
      the Leptothrix strains clustered in two separate lineages that were approximately
      equidistant from the S. natans cluster. This finding suggests that the tentative
      species "L. discophora" needs to be more clearly defined and compared with other
      species belonging to the genus Leptothrix.

PMID- 8573493
TI  - Tolumonas auensis gen. nov., sp. nov., a toluene-producing bacterium from anoxic
      sediments of a freshwater lake.
AB  - A new toluene-producing bacterium, strain TA 4T (T = type strain), was isolated
      from anoxic sediments of a freshwater lake. The individual cells of this organism
      were nonmotile, gram-negative rods that were 0.9 to 1.2 by 2.5 to 3.2 microns.
      The optimum temperature and pH for growth were 22 degrees C and pH 7.2,
      respectively. The G+C content of the DNA was 49 mol%. Toluene was produced from
      phenylalanine, phenylpyruvate, phenyllactate, and phenylacetate, and phenol was
      produced from tyrosine. Both the presence of a carbon source and the presence of
      a toluene precursor were essential for initiation of toluene production.
      Bacterial growth occurred under oxic and anoxic conditions. Acetate, ethanol, and
      formate were the major fermentation products of the bacterium when it was grown
      on glucose. The major lipoquinones were ubiquinone 8 and menaquinone 8 under both
      oxic and anoxic growth conditions. On the basis of the results of a 16S ribosomal
      DNA sequence analysis, we concluded that this organism is a member of the gamma
      subclass of the Proteobacteria, and we suggest the name Tolumonas auensis for
      this species.

PMID- 8573494
TI  - Use of an rRNA internal transcribed spacer region to distinguish phylogenetically
      closely related species of the genera Zygosaccharomyces and Torulaspora.
AB  - Analyses of the sequences of the small-subunit (18S) rRNA gene and two internal
      transcribed spacers (ITSs), ITS1 and ITS2, revealed that members of the yeast
      genera Torulaspora and Zygosaccharomyces are phylogenetically intermixed. Despite
      some minor differences in 18S rRNA-, ITS1-, and ITS2-derived trees, in general
      the patterns of the relationships inferred from the three chronometers were in
      good agreement. The ITS sequences of Torulaspora and Zygosaccharomyces species
      exhibited far greater interspecies differences than the 18S rRNA sequences and
      were better than 18S rRNA sequences for measuring close genealogical
      relationships. Despite the existence of interstrain ITS sequence variation in
      some species, it is possible to identify conserved regions in both ITSs that are
      useful in species differentiation.

PMID- 8573495
TI  - Phylogenetic analysis of Butyrivibrio strains reveals three distinct groups of
      species within the Clostridium subphylum of the gram-positive bacteria.
AB  - The phylogenetic positions of 40 Butyrivibrio strains were determined by
      performing a comparative sequence analysis of the 16S rRNA genes of these
      organisms. We found that all of the strains which we studied belong to cluster
      XIVa (M. D. Collins, P. A. Lawson, A. Willems, J. J. Cordoba, J.
      Fernandez=Garayzabal, P. Garcia, J. Cai, H. Hippe, and J. A. E. Farrow, Int. J.
      Syst. Bacteriol. 44:812-826, 1994) of the Clostridium subphylum of the gram
      positive bacteria, which also includes several Clostridium, Coprococcus,
      Eubacterium, and Ruminococcus species. We also found that the Butyrivibrio
      strains which we examined were genotypically heterogeneous and exhibited 12
      distinct rRNA sequence types. The 12 rRNA sequence types formed three distinct
      lineages in cluster XIVa, which were separate from each other and from all other
      species belonging to this cluster. One lineage consisted of strains which
      exhibited a single rRNA type and corresponded to the species Butyrivibrio
      crossotus. The second lineage consisted of 12 strains designated Butyrivibrio
      fibrisolvens which exhibited seven distinct rRNA sequence types. The type strain
      of B. fibrisolvens was a member of this lineage, but its position was peripheral.
      The third lineage comprised 26 B. fibrisolvens strains which exhibited four
      distinct rRNA sequence types. Tree topology and sequence divergence
      considerations indicated that the three lineages correspond to three separate
      genera and that the genus Butyrivibrio should be restricted to the group that
      contains the type strain of B. fibrisolvens.

PMID- 8573496
TI  - 16S rRNA gene sequence analysis relative to genomovars of Pseudomonas stutzeri
      and proposal of Pseudomonas balearica sp. nov.
AB  - We compared the 16S rRNA gene sequences of 14 strains of Pseudomonas stutzeri,
      including type strain CCUG 11256 and strain ZoBell (= ATCC 14405), which
      represented the seven P. stutzeri genomovars (DNA-DNA similarity groups) that
      have been described. Our sequence analysis revealed clusters which were highly
      correlated with genomovar clusters derived from DNA-DNA hybridization data. In
      addition, we identified signature nucleotide positions for each genomovar. We
      found that the 16S rRNA gene sequences of genomovar 6 strains SP1402T (T = type
      strain) and LS401 were different enough from the sequence of the type strain of
      P. stutzeri that these organisms should be placed in a new species, Pseudomonas
      balearica. The type strain of P. balearica is strain SP1402 (= DSM 6083).

PMID- 8573497
TI  - Serpulina pilosicoli sp. nov., the agent of porcine intestinal spirochetosis.
AB  - Phenotypic and genetic traits of porcine intestinal spirochete strain P43/6/78T
      (= ATCC 51139T) (T = type strain), which is pathogenic and weakly beta-hemolytic,
      were determined in order to confirm the taxonomic position of this organism and
      its relationships to previously described species of intestinal spirochetes. In
      BHIS broth, P43/6/78T cells had a doubling time of 1 to 2 h and grew to a maximum
      cell density of 2 x 10(9) cells per ml at 37 to 42 degrees C. They hydrolyzed
      hippurate, utilized D-glucose, D-fructose, sucrose, D-trehalose, D-galactose, D
      mannose, maltose, N-acetyl-D-glucosamine, D-glucosamine, pyruvate, L-fucose, D
      cellobiose, and D-ribose as growth substrates, and produced acetate, butyrate,
      ethanol, H2, and CO2 as metabolic products. They consumed substrate amounts of
      oxygen and had a G+C content (24.6 mol%) similar to that of Serpulina
      hyodysenteriae B78T (25.9 mol%). Phenotypic traits that could be used to
      distinguish strain P43/6/78T from S. hyodysenteriae and Serpulina innocens
      included its ultrastructural appearance (each strain P43/6/78T cell had 8 or 10
      periplasmic flagella, with 4 or 5 flagella inserted at each end, and the cells
      were thinner and shorter and had more pointed ends than S. hyodysenteriae and S.
      innocens cells), its faster growth rate in liquid media, its hydrolysis of
      hippurate, its lack of beta-glucosidase activity, and its metabolism of D-ribose.
      DNA-DNA relative reassociation experiments in which the S1 nuclease method was
      used revealed that P43/6/78T was related to, but was genetically distinct from,
      both S. hyodysenteriae B78T (level of sequence homology, 25 to 32%) and S.
      innocens B256T (level of sequence homology, 24 to 25%). These and previous
      results indicate that intestinal spirochete strain P43/6/78T represents a
      distinct Serpulina species. Therefore, we propose that strain P43/6/78 should be
      designated as the type strain of a new species, Serpulina pilosicoli.

PMID- 8573498
TI  - Genomic variability of Staphylococcus aureus and the other coagulase-positive
      Staphylococcus species estimated by macrorestriction analysis using pulsed-field
      gel electrophoresis.
AB  - The genomic DNAs of 95 culture collection and hospital Staphylococcus aureus
      subsp. aureus strains of various origins, as well as the genomic DNAs of other
      coagulase-positive Staphylococcus species, were cleaved with restriction
      endonuclease SmaI and subjected to pulsed-field gel electrophoresis. The levels
      of similarity of the SmaI restriction patterns of the S. aureus subsp. aureus
      strains varied from 30 to 100%, which is considered characteristic of this
      species; thus, these organisms belonged to the same species restriction group.
      Within this range of similarity values 13 S. aureus intraspecies restriction
      groups were identified, and each group consisted of strains whose levels of
      similarity ranged from 65 to 100%. S. aureus subsp. aureus CCM 885T (T = type
      strain) belonged to the major intraspecies restriction group that comprised 39%
      of the S. aureus strains which we studied. The strains of the other coagulase
      positive staphylococci, including Staphylococcus aureus subsp. anaerobius,
      Staphylococcus hyicus, Staphylococcus intermedius, Staphylococcus delphini, and
      Staphylococcus schleiferi subsp. coagulans, clustered with their type strains in
      separate restriction groups. S. aureus subsp. aureus exhibited almost no
      similarity to these species. We found 44-kb SmaI fragments in all of the S.
      aureus subsp. aureus and S. aureus subsp. anaerobius strains studied, and these
      fragments are considered characteristic of the species S. aureus. The high level
      of homology of these fragments was confirmed by the results of DNA hybridization
      experiments in which we used representatives of individual intraspecies
      restriction groups. Of the other staphylococci studied, only Staphylococcus
      epidermidis and one strain of S. hyicus contained these fragments. However, the
      levels of homology between these fragments and the fragments of S. aureus were
      found to be very low.

PMID- 8573499
TI  - Spiroplasma diminutum sp. nov., from Culex annulus mosquitoes collected in
      Taiwan.
AB  - Initially, strain CUAS-1T (T = type strain), which was isolated from a frozen
      triturate of Culex annulus mosquitoes collected in Taiwan, was thought to be a
      member of spiroplasma group VII. This placement was based on the spiroplasma
      deformation test titer observed when strain CUAS-1T spiroplasmas were tested with
      Spiroplasma monobiae MQ-1T antiserum. The results of subsequent reciprocal
      spiroplasma deformation, metabolism inhibition, and growth inhibition tests
      clearly revealed that strain CUAS-1T is not serologically related to previously
      described spiroplasma groups (groups I to XXIV) and thus is a representative of a
      new group, group XXV. Strain CUAS-1T was characterized by using the minimal
      standards for mollicute species descriptions. During logarithmic-phase growth,
      strain CUAS-1T cells are characteristically very short helices with 1.5 to 2
      helical turns (1 to 2 microns), highly motile, and bounded by a single trilaminar
      membrane and form granular colonies with satellites when the organism is grown
      aerobically on MID medium containing 1.6% agar. Growth in MID broth occurs at
      temperatures ranging from 10 to 37 degrees C, and the optimum temperature is 30
      degrees C. Substrate utilization tests revealed that cholesterol is required for
      growth, that glucose is hydrolyzed, and that arginine is not hydrolyzed both in
      the presence and in the absence of glucose. The genome of strain CUAS-1T is 1,080
      kbp long, and the guanine-plus-cytosine content is 26 +/- 1 mol%. On the basis of
      the results of our studies we propose that strain CUAS-1T (group XXV) should be
      placed in a new species, Spiroplasma diminutum. Strain CUAS-1 (= ATCC 49235) is
      the type strain of S. diminutum.

PMID- 8573501
TI  - Agrococcus jenensis gen. nov., sp. nov., a new genus of actinomycetes with
      diaminobutyric acid in the cell wall.
AB  - Two strains of a new gram-positive coryneform bacterium isolated from soil and
      from a sandstone surface are described. Strain 2002-39/1T (T = type strain) is a
      coccoid, nonmotile, non-acid-fast, microaerophilic organism. The menaquinones of
      this strain are MK-12 and MK-11, and the main components of the whole-cell sugars
      are glucose and rhamnose. No mycolic acids are present. The G+C content of the
      DNA is 74 mol%. Comparative 16S ribosomal DNA studies and a cell wall analysis
      revealed that this strain represents a new genus belonging to the group of
      actinomycetes that have diaminobutyric acid in their peptidoglycans. The second
      strain, strain ST54, which was isolated from a sandstone surface, had the same
      characteristic features as strain 2002-39/1T. The name Agrococcus jenensis gen.
      nov., sp. nov., is proposed for these organisms. The type strain is strain 2002
      39/1, which has been deposited in the German Collection of Microorganisms and
      Cell Cultures as strain DSM 9580.

PMID- 8573500
TI  - Rhodococcus percolatus sp. nov., a bacterium degrading 2,4,6-trichlorophenol.
AB  - A bacterial strain that was able to mineralize 2,4,6-trichlorophenol was isolated
      from a chlorophenol-fed percolator and was identified as a member of the genus
      Rhodococcus on the basis of chemotaxonomic characteristics and 16S RNA
      phylogenetic inference data. This organism (strain MBS1T [T = type strain])
      exhibited a typical irregular rod-coccus cycle, and the cells had fimbria-like
      structures on their surfaces. The diagnostic cell wall amino acid was meso
      diaminopimelic acid, and the sugars were arabinose and galactose; the mycolic
      acids contained 46 to 54 carbon atoms. The main menaquinone was MK-8(H2), and MK
      9(H2) was a minor component. The cellular phospholipids were
      phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositolmannoside,
      phosphatidylglycerol, and diphosphatidylglycerol. Tuberculostearic acid was
      present. The whole-cell fatty acids were straight-chain acids with 14 to 18 C
      atoms. The G+C content of the DNA was 67.4 mol%. This organism grew on sucrose,
      pyruvate, and 2,4,6-trichlorophenol, and it oxidized a large number of carbon
      compounds, including catechol, 3-hydroxyphenylacetic acid, and phenol. It also
      exhibited beta-galactosidase, urease, and 2-acetyl-lactate decarboxylase
      activities. On a phylogenetic tree that was based on 16S ribosomal DNA gene
      sequences strain MBS1T was found among the rhodococci on an independent branch.
      On the basis of the chemotaxonomic and phenotypic characteristics of strain MBS1T
      and its phylogenetic position we suggest that this bacterium should be placed in
      a new species, Rhodococcus percolatus; the specific epithet was chosen because
      the organism was isolated by using an enriched percolator. The type strain is
      strain MBS1.

PMID- 8573502
TI  - Phylogenetic relationships among Rhizobium species nodulating the common bean
      (Phaseolus vulgaris L.).
AB  - The phylogenetic relationships among Rhizobium species that nodulate Phaseolus
      vulgaris (common bean) were determined by directly sequencing the amplified 16S
      ribosomal DNA genes of these organisms. The bean strains formed four separate
      clusters. One cluster was composed of Rhizobium leguminosarum bv. trifolii, R.
      leguminosarum bv. viciae, and R. leguminosarum bv. phaseoli. Two other clusters
      comprised Rhizobium etli and Rhizobium tropici, and the fourth cluster contained
      a single bean-nodulating strain. Data for species identification were obtained
      from DNA-DNA reassociation experiments. The levels of DNA relatedness among
      strains belonging to the three biovars of R. leguminosarum ranged from 58 to 67%.
      The levels of DNA relatedness between R. leguminosarum bv. phaseoli and R. etli
      and R. tropici ranged from 43 to 45% and 13 to 16%, respectively. The levels of
      DNA relatedness between the strain belonging to the fourth cluster and strains of
      the other three Rhizobium species that nodulate beans were less than 10%.

PMID- 8573503
TI  - Analyses of the genomes of chlamydial isolates from ruminants and pigs support
      the adoption of the new species Chlamydia pecorum.
AB  - Analysis of the genomic DNAs of chlamydial isolates from sheep, cattle, and pigs
      was performed by Southern blot hybridization and by restriction endonuclease (RE)
      profiling of DNA amplified by PCR. The hybridization probes were derived from
      whole genomic DNA, the major outer membrane protein (MOMP) gene, the 16S rRNA
      gene, and an avian Chlamydia psittaci isolate plasmid. The PCR analysis used
      targets in the MOMP gene, the 16S rRNA gene, and the 60-kDa cysteine-rich protein
      gene. Together, the results showed that although there was considerable
      heterogeneity in the DNA sequence in the MOMP gene region, all the isolates had
      the same underlying total genomic RE profiles and yielded identical RE profiles
      for the rRNA and 60-kDa-protein gene regions. Most of the isolates were found to
      hybridize with the plasmid probe. Comparison of the MOMP sequence of one of the
      isolates (P787) with that of a known Chlamydia pecorum strain together with the
      results of the RE analyses allowed the conclusion that the isolates should all be
      classified within this new species.

PMID- 8573505
TI  - Nocardia pseudobrasiliensis sp. nov., a new species of Nocardia which groups
      bacterial strains previously identified as Nocardia brasiliensis and associated
      with invasive diseases.
AB  - We studied five strains of a new Nocardia taxon recently identified among
      Nocardia brasiliensis strains associated with invasive diseases (R. J. Wallace,
      Jr., B. A. Brown, Z. Blacklock, R. Ulrich, K. Jost, J. M. Brown, M. M. McNeil, G.
      Onyi, V. A. Steingrube, and J. Gibson, J. Clin. Microbiol. 33:1528-1533, 1995) to
      determine their taxonomic status. Several characteristics of these organisms,
      including the presence of chemotype IV cell walls, nocardomycolic acids, a
      predominant menaquinone similar to that of Nocardia asteroides ATCC 19247T (T =
      type strain), and G+C contents ranging from 67 to 68 mol%, are characteristics of
      the genus Nocardia. Phylogenies based on small-subunit ribosomal DNA sequences
      clearly confirmed that all five strains belong to the genus Nocardia and occur on
      a single branch that is clearly distinct from N. brasiliensis. This branch forms
      a clade with Nocardia vaccinii, Nocardia nova, Nocardia otitidiscaviarum, and
      Nocardia seriolae. The five new strains exhibited high levels of DNA relatedness
      with each other, as determined by DNA-DNA hybridization experiments (S1 nuclease
      procedure), but not with N. brasiliensis strains or with strains of the four
      phylogenetically related Nocardia species mentioned above. The five new strains
      differ from N. brasiliensis in the following characteristics: mycolic acid
      pattern, decomposition of adenine, nitrate reduction, and antimicrobial agent
      susceptibilities. Therefore, we propose that these strains belong to a new
      species, Nocardia pseudobrasiliensis. The type strain is strain ATCC 51512, which
      was isolated from a leg abscess on a patient suffering from ulcerative colitis.

PMID- 8573504
TI  - Sutterella wadsworthensis gen. nov., sp. nov., bile-resistant microaerophilic
      Campylobacter gracilis-like clinical isolates.
AB  - Campylobacter gracilis (formerly Bacteroides gracilis) is an asaccharolytic,
      nitrate-positive, urease-negative organism that requires formate and fumarate or
      hydrogen as a growth additive and may pit agar media. Clinical isolates that were
      obtained primarily from appendiceal and peritoneal fluid specimens and initially
      were identified in our laboratory as B. gracilis were later found to include
      "unusual" strains that could be distinguished by biochemical and genetic
      criteria. These unusual C. gracilis strains were bile resistant, could not reduce
      tetrazolium chloride under aerobic conditions if formate and fumarate were added
      to the medium, and could grow in the presence of 2 or 6% oxygen if no blood was
      added to the medium. C. gracilis, other campylobacters, and the unusual strains
      produced distinctive dehydrogenase patterns when gels were incubated
      anaerobically. A cellular fatty acid analysis revealed that the cluster formed by
      the unusual organisms was distinct from the (separate) clusters formed by C.
      gracilis, Bacteroides ureolyticus, and other Campylobacter species. 16S rRNA
      sequence data indicated that these organisms are not related phylogenetically to
      either C. gracilis or other Campylobacter species; the most closely related taxa
      as determined by rRNA sequence analysis were unrelated aerobes (members of the
      genera Bordetella, Alcaligenes, Rhodocyclus, and Comamonas). DNA homology data
      confirmed that these taxa are separate groups. Our data indicate that the unusual
      organisms are members of a new genus and new species, for which we propose the
      name Sutterella wadsworthensis. The type strain of S. wadsworthensis is strain
      WAL 9799 (= ATCC 51579).

PMID- 8573506
TI  - Fervidobacterium gondwanense sp. nov., a new thermophilic anaerobic bacterium
      isolated from nonvolcanically heated geothermal waters of the Great Artesian
      Basin of Australia.
AB  - A new thermophilic, carbohydrate-fermenting, obligately anaerobic bacterial
      species was isolated from a runoff channel formed from flowing bore water from
      the geothermally heated aquifer of the Great Artesian Basin of Australia. The
      cells of this organism were nonsporulating, motile, gram negative, and rod shaped
      and generally occurred singly or in pairs. The optimum temperature for growth was
      65 to 68 degrees C, and no growth occurred at temperatures below 44 degrees C or
      above 80 degrees C. Growth was inhibited by 10 micrograms of lysozyme per ml, 10
      micrograms of penicillin per ml, 10 micrograms of tetracycline per ml, 10
      micrograms of phosphomycin per ml, 10 micrograms of vancomycin per ml, 10
      micrograms of vancomycin per ml, and NaCl concentrations greater than 0.2%. The
      optimum pH for growth was 7.0, and no growth occurred at pH 5.5 or 8.5. The DNA
      base composition was 35 mol% guanine plus cytosine, as determined by thermal
      denaturation. The end products of glucose fermentation were lactate, acetate,
      ethanol, CO2, and H2. Sulfur, but not thiosulfate, sulfite, or sulfate, was
      reduced to sulfide. Phase-contrast microscopy of whole cells and an electron
      microscopic examination of thin sections of cells revealed the presence of single
      terminal spheroids, a trait common in members of the genus Fervidobacterium.
      However, a phylogenetic analysis of the 16S rRNA sequence revealed that the new
      organism could not be assigned to either of the two previously described
      Fervidobacterium species. On the basis of these observations, we propose that the
      new organism should be designated a new Fervido-bacterium species,
      Fervidobacterium gondwanense. The type strain of this species is strain AB39 (=
      Australian Collection of Microorganisms strain ACM 5017.

PMID- 8573507
TI  - Reclassification of Paenibacillus (formerly Bacillus) pulvifaciens (Nakamura
      1984) Ash et al. 1994, a later subjective synonym of Paenibacillus (formerly
      Bacillus) larvae (White 1906) Ash et al. 1994, as a subspecies of P. larvae, with
      emended descriptions of P. larvae as P. larvae subsp. larvae and P. larvae subsp.
      pulvifaciens.
AB  - A polyphasic taxonomic study of four strains of Paenibacillus larvae and four
      strains of Paenibacillus pulvifaciens (including duplicates of both type strains)
      supported the reclassification of both former Bacillus species into one species,
      P. larvae. Our conclusions were based on morphological and Analytab Products
      (API) tests, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)
      of whole-cell proteins, gas chromatography of methylated fatty acids, pyrolysis
      mass spectrometry, DNA-DNA binding, and the following genomic fingerprinting
      methods: amplified ribosomal DNA restriction analysis, random amplified
      polymorphic DNA analysis, and AFLP analysis. The last method is a novel high
      resolution DNA fingerprinting technique based on the selective amplification of
      restriction fragments. Despite more than 90% DNA relatedness between the strains
      studied, SDS-PAGE of whole-cell proteins, biochemical tests, and DNA
      fingerprinting (AFLP) distinguished between the P. larvae and P. pulvifaciens
      strains at the subspecies level. Taking this evidence along with differences in
      pathogenicity, we propose to reclassify the honeybee pathogens P. larvae and P.
      pulvifaciens as P. larvae subsp. larvae and P. larvae subsp. pulvifaciens. An
      emended description of the species and descriptions of the subspecies are given.
      The type strains are P. larvae subsp. larvae ATCC 9545 (LMG 9820) and P. larvae
      subsp. pulvifaciens NRRL B-3685 (LMG 6911 and ATCC 13537).

PMID- 8573510
TI  - Eubacterium minutum sp. nov., isolated from human periodontal pockets.
AB  - We describe Eubacterium minutum sp. nov., which was isolated from human
      periodontal pockets. This new species was established on the basis of DNA-DNA
      hybridization data. The guanine-plus-cytosine content of its DNA is 38 to 40
      mol%. The results of differential biochemical and enzymatic tests are described.
      The type strain of this species is strain M-6.

PMID- 8573509
TI  - Spirochaeta alkalica sp. nov., Spirochaeta africana sp. nov., and Spirochaeta
      asiatica sp. nov., alkaliphilic anaerobes from the Continental Soda Lakes in
      Central Asia and the East African Rift.
AB  - During a study of microbial communities in athalassic bodies of water, three new
      species within the genus Spirochaeta were described. These are alkaliphilic
      Spirochaeta alkalica sp. nov. Z-7491 (DSM 8900) and halophilic S. africana sp.
      nov. Z-7692 (DSM 8902) from the soda-depositing Lake Magadi in Central Africa and
      haloalkaliphilic S. asiatica sp. nov. Z-7591 (DSM 8901) from Lake Khatyn, Central
      Asia. These mesophilic spirochetes develop at pHs of > 9 as anaerobic
      saccharolytic dissipotrophs. The DNA base compositions (moles percent G+C) of the
      strains were as follows: S. alkalica Z-7491, 57.1; S. africana Z-7692, 56.1; and
      S. asiatica Z-7591, 49.2. The optimum growth parameters (temperature, pH, and
      NaCl concentration [percent, wt/vol], respectively) were as follows: for S.
      alkalica Z-7491, 35 degrees C, 9.2, and 5 to 7%; for S. africana Z-7692, 35
      degrees C, 9.3, and 5 to 7%; and for S. asiatica Z-7591, 35 degrees C, 8.9, and 3
      to 6%. The products of glucose fermentation were acetate, hydrogen, ethanol, and
      lactate, in different proportions, for S. alkalica and S. africana; for S.
      asiatica, they were acetate, ethanol, and lactate. S. asiatica is strictly
      anaerobic, while S. alkalica and S. africana are rather aerotolerant. All three
      species group within the radiation of the majority of the species of the genus
      Spirochaeta. Studies of the genes encoding 16S rRNA indicate a possible fanning
      out of the phylogenetic tree of spirochetes.

PMID- 8573508
TI  - Semantide- and chemotaxonomy-based analyses of some problematic phenotypic
      clusters of slowly growing mycobacteria, a cooperative study of the International
      Working Group on Mycobacterial Taxonomy.
AB  - During previous cooperative numerical taxonomic studies of slowly growing
      mycobacteria, the International Working Group on Mycobacterial Taxonomy described
      a number of strains whose taxonomic status was ambiguous. A new study of DNA,
      RNA, and proteins from 66 of these organisms was performed to correlate their
      properties with phenotypic clustering behavior; the results of this study
      permitted 51 of the strains studied to be assigned to known species. The methods
      used to characterize the semantides included nucleotide sequencing and assessment
      of levels of semantide relatedness by affinity binding techniques, including
      whole DNA-DNA hybridization, probe hybridization, and antibody binding. There was
      good overall agreement between the phenotypic and chemotaxonomic clusters and the
      groups of organisms identified by semantide analyses. Our results supported the
      conclusion that we should continue to rely on polyphasic taxonomy to provide
      satisfactory systematic resolution of members of the genus Mycobacterium. We
      identified no single 16S rRNA interstrain nucleotide sequence difference value
      that unequivocally defined species boundaries. DNA-DNA hybridization remains the
      gold standard, but common resources are needed to permit DNA-DNA hybridization
      analyses to be made available to laboratories that are not prepared to use this
      technology. One of the large novel clusters which we studied corresponds to the
      recently described species Mycobacterium interjectum, a pathogen that resembles
      the nonpathogen Mycobacterium gordonae phenotypically. We also identified strains
      that appear to represent ribovars of Mycobacterium intracellulare which do not
      react with the commercial diagnostic probes that are currently used for
      identification of this species. Other branches or clusters consisted of too few
      strains to permit a decision about their taxonomic status to be made.

PMID- 8573511
TI  - A reconsideration of species related to Saccharomyces dairensis (Naganishi).
AB  - A study of DNA reassociation kinetics and electrophoretic karyotypes of several
      strains classified as Saccharomyces castellii, Saccharomyces dairensis, and
      Pachytichospora transvaalensis strains revealed that the group included members
      of at least five distinct species. Two of the four strains classified as P.
      transvaalensis exhibited very high levels of DNA sequence homology with the type
      strain of S. castellii, while the type strain and another strain demonstrated
      intermediate levels of relatedness to the type strains of the unrelated taxa S.
      castellii and S. dairensis. Five strains that were classified as S. dairensis
      strains were not related to the type strains of the taxa studied. Two of these
      strains exhibited intermediate relatedness (65% base sequence homology), while
      another pair exhibited a level of DNA reassociation of 97%. The remaining strain
      was distinct from all of the other strains studied on the basis of both DNA base
      sequences and electrophoretic karyotype data.

PMID- 8573512
TI  - Synonomy of the yeast genera Saccharomyces Meyen ex Hansen and Pachytichospora
      van der Walt.
AB  - The type strains and other strains of the phenotypically similar taxa
      Saccharomyces castelli Capriotti, Saccharomyces dairensis Naganishi, and
      Pachytichospora transvaalensis van der Walt were studied by comparing the
      ascospore morphologies of these organisms by examining ultrathin sections by
      transmission electron microscopy. The results of this study and another
      investigation of DNA base sequence homology demonstrated that the monotypic genus
      Pachytichospora van der Walt is invalid. We propose that the species
      Saccharomyces transvaalensis van der Walt should be reinstated.

PMID- 8573513
TI  - Arbitrarily primed PCR analysis of Mycoplasma hyopneumoniae field isolates
      demonstrates genetic heterogeneity.
AB  - Mycoplasma hyopneumoniae is the primary agent of mycoplasmal pneumonia in swine.
      In this study we performed an arbitrarily primed PCR (AP-PCR) analysis, in which
      low-stringency amplification with a single primer was used, to investigate
      genetic variability in M. hyopneumoniae strains and field isolates. We performed
      preliminary experiments to examine the efficacy of 40 different 10-mer
      oligonucleotides for priming an AP-PCR with M. hyopneumoniae JT (T = type strain)
      chromosomal DNA. On the basis of our results, we selected primers OPA-3, OPA-17,
      and OPB-10 for use in an analysis performed with 23 field isolates. The most
      informative results were obtained with primer OPA-3. A total of 21 of 23 clinical
      isolates produced multiband patterns with this primer, while 2 isolates failed to
      produce any detectable bands. Our data show that M. hyopneumoniae is genetically
      diverse and that M. hyopneumoniae strains can be divided into at least six
      epidemiological subgroups on the basis of AP-PCR results.

PMID- 8573514
TI  - Species-specific sequences at the omp2 locus of Brucella type strains.
AB  - A DNA sequence analysis of the omp2 locus of Brucella type strains revealed
      nucleotide differences that can be used for species identification. We developed
      specific probes which were used to verify the observed differences among the type
      strains following PCR amplification of portions of the omp2 locus.

PMID- 8573515
TI  - Classification of the genus Mobiluncus based on comparative partial 16S rRNA gene
      analysis.
AB  - On the basis of partial 16S rRNA gene sequences and the results of Southern blot
      analyses, we confirmed the division of the genus Mobiluncus into the species
      Mobiluncus curtisii and Mobiluncus mulieris. Division of M. curtisii into M.
      curtisii subsp. curtisii and M. curtisii subsp. holmesii was not supported by our
      data.

PMID- 8573516
TI  - Reclassification of Lactobacillus casei subsp. casei ATCC 393 and Lactobacillus
      rhamnosus ATCC 15820 as Lactobacillus zeae nom. rev., designation of ATCC 334 as
      the neotype of L. casei subsp. casei, and rejection of the name Lactobacillus
      paracasei.
AB  - The type strain of Lactobacillus casei subsp. casei (ATCC 393) exhibits low
      levels of DNA homology with other strains of L. casei subsp. casei (8 to 46%) and
      strains of Lactobacillus paracasei (30 to 50%), but exhibits a level of DNA
      similarity of 80% with Lactobacillus rhamnosus ATCC 15820, the original type
      strain of "Lactobacterium zeae" Kuznetsov 1959. Strains ATCC 393T (T = type
      strain) and ATCC 15820T are members of one protein profile cluster that is
      separate from the other Lactobacillus spp. The randomly amplified polymorphic DNA
      PCR profile of strain ATCC 393T is also different from the profiles obtained for
      the other species. L. casei ATCC 334T is genetically closely related to L. casei
      subsp. casei strains (71 to 97%) and L. paracasei strains (71 to 91%), is a
      member of the same protein profile cluster as these organisms, and shares several
      DNA amplicons with L. paracasei strains. On the basis of these results, we
      propose that L. casei subsp. casei ATCC 393T and L. rhamnosus ATCC 15820 should
      be reclassified as members of Lactobacillus zeae nom. rev. (type strain, ATCC
      15820), that strain ATCC 334 should be designated the neotype strain of L. casei
      subsp. casei, and that the name L. paracasei should be rejected.

PMID- 8573517
TI  - Phylogenetic analysis of Fusobacterium prausnitzii based upon the 16S rRNA gene
      sequence and PCR confirmation.
AB  - In order to develop a PCR method to detect Fusobacterium prausnitzii in human
      feces and to clarify the phylogenetic position of this species, its 16S rRNA gene
      sequence was determined. The sequence described in this paper is different from
      the 16S rRNA gene sequence is specific for F. prausnitzii, and the results of
      this assay confirmed that F. prausnitzii is the most common species in human
      feces. However, a PCR assay based on the original GenBank sequence was negative
      when it was performed with two strains of F. prausnitzii obtained from the
      American Type Culture Collection. A phylogenetic tree based on the new 16S rRNA
      gene sequence was constructed. On this tree F. prausnitzii was not a member of
      the Fusobacterium group but was closer to some Eubacterium spp. and located
      between Clostridium "clusters III and IV" (M.D. Collins, P.A. Lawson, A. Willems,
      J.J. Cordoba, J. Fernandez-Garayzabal, P. Garcia, J. Cai, H. Hippe, and J.A.E.
      Farrow, Int. J. Syst. Bacteriol. 44:812-826, 1994).

PMID- 8573518
TI  - "Candidatus Microthrix parvicella", a filamentous bacterium from activated sludge
      sewage treatment plants.
AB  - "Candidatus Microthrix parvicella" is a filamentous bacterium that grows with
      great difficulty in cultures from the mixed liquor of activated sludge sewage
      treatment plants. It is gram positive, and the ultrastructure of its cell walls
      has been determined to be of the gram-positive type by electron microscopical
      examination. Phylogenetically, it is a deep-branching member of the subphylum
      actinomycetes within the gram-positive phylum of the domain Bacteria. As for
      phenotypic features, it is known that the organism contains a polyphosphate
      inclusions and that it is catalase positive. In mixed cultures in activated
      sludge plants and in pure culture in the laboratory, it has a characteristic and
      distinctive winding filamentous morphology, with filaments hundreds of
      micrometers long.

PMID- 8573519
TI  - The phylogeny of Methanopyrus kandleri.
AB  - The phylogenetic position of Methanopyrus kandleri has been difficult to
      determine because reconstructions of phylogenetic trees based on rRNA sequences
      have been ambiguous. The most probable trees determined by most algorithms place
      the genus Methanopyrus at the base of a group that includes the halobacteria and
      the methanogens and their relatives, although occasionally some algorithms place
      this genus near the eocytes (the hyperthermophilic, sulfur-metabolizing
      prokaryotes), suggesting that it may belong to this lineage. In order to resolve
      the phylogeny of the genus Methanopyrus, we determined the sequence of an
      informative region of elongation factor 1-alpha that contains an 11-amino-acid
      insertion in eocytes and eukaryotes which is replaced by a 4-amino-acid insertion
      in methanogens, halobacteria, and eubacteria. On the basis of the results of our
      elongation factor 1-alpha gene analysis, we concluded that the genus Methanopyrus
      diverged from the eocyte branch before the eukaryotic and eocyte lineages
      separated and therefore is not an eocyte.

PMID- 8573520
TI  - Karyotyping of fluconazole-resistant yeasts with phenotype reported as Candida
      krusei or Candida inconspicua.
AB  - The yeasts Candida krusei and Candida inconspicua have similar phenotypes, which
      may make discrimination of these organisms difficult. In this study we determined
      the karyotypes of 51 isolates of these two yeast species by contour-clamped
      homogeneous electric field electrophoresis. We found that the 43 isolates that
      had the C. krusei phenotype had three karyotype-specific characteristics. These
      isolates produced either two or three bands between 2,000 and 3,000 kb and no
      band between 1,300 and 2,000 kb, and there was either a single bright band at
      1,300 or 1,200 kb or two separate bands at 1,300, 1,200, or 1,100 kb. Using this
      technique, we were able to distinguish 27 different C. krusei types on the basis
      of band variations. The seven isolates identified as C. inconspicua on the basis
      of phenotype differed in that they produced at least one band between 1,300 and
      2,000 kb. These isolates produced six to nine bands, in contrast to C. krusei
      strains, which produced three to six bands. The MIC of fluconazole for all of the
      isolates was at least 12.5 mg/liter, as determined by a broth dilution method.

PMID- 8573521
TI  - Molecular and chemical taxonomic differentiation of Candida boidinii Ramirez
      strains.
AB  - Molecular and chemical taxonomic characteristics, including DNA base composition,
      electrophoretic karyotype, restriction fragment length polymorphism of genes
      coding for rRNA, cellular fatty acid composition, and ubiquinone systems, were
      studied for 19 strains of Candida boidinii Ramirez. Electrophoretic karyotype and
      restriction fragment length polymorphism demonstrated marked differences among
      these strains. A combination of molecular and chemical analyses can serve as a
      reliable tool for culture authentication and quality control of industrial
      strains.

PMID- 8573522
TI  - Characterization of Legionella species by numerical analysis of whole-cell
      protein electrophoresis.
AB  - The results of a computer-assisted whole-cell protein sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) analysis of 291 isolates and 74
      reference strains belonging to all known species of the genus Legionella revealed
      that the majority of the species of this genus can be adequately identified by
      this method. The type strain of Legionella bozemanii did not cluster with the
      other strains of this species, and the only strain of Legionella geestiana
      available clustered with the strains of Legionella feeleii. When we performed a
      numerical analysis by omitting certain portions of the pattern containing dense
      bands, all of the species could be distinguished. Our results also show that the
      type strains of Legionella nautarum and Legionella londiniensis deposited in the
      National Collection of Type Cultures do not correspond to the type strains
      deposited in the American Type Culture Collection. We used the results of a fatty
      acid and ubiquinone composition analysis to complement the SDS-PAGE results for
      several strains whose identities as determined by indirect immunofluorescence
      were doubtful. Computer-assisted SDS-PAGE of whole-cell proteins can be used in
      the classification of Legionella species and to identify and screen large numbers
      of isolates for further, in-depth taxonomic studies of smaller numbers of
      strains.

PMID- 8573523
TI  - Genomic diversity and differentiation among phytoplasma strains in 16S rRNA
      groups I (aster yellows and related phytoplasmas) and III (X-disease and related
      phytoplasmas).
AB  - Conserved gene sequences, including 16S rRNA and ribosomal protein gene
      sequences, were used to evaluate genetic variations in phytoplasma strains
      belonging to 16S rRNA groups I (aster yellows and related phytoplasmas) and III
      (X-disease and related phytoplasmas). We used PCR to amplify the sequences of the
      16S ribosomal DNA and a segment of the ribosomal protein gene operon (encoding
      the 3' region of rps19, all of rp122, and rps3) from diverse phytoplasma group I
      and III strains. Additional chromosomal gene sequences of group I strains were
      also amplified. The PCR products amplified from members of each group of
      phytoplasmas were compared by performing restriction fragment length polymorphism
      (RFLP) analyses. On the basis of the RFLP patterns observed and similarity
      coefficients derived from combined RFLP analyses, the phytoplasma strains
      belonging to groups I and III were placed in distinct 16S rRNA, ribosomal
      protein, and 16S rRNA-ribosomal protein subgroups. Analyses of two or more
      conserved gene sequences revealed that members of the two groups were more
      diverse than previously thought. Subgroup differentiation on the basis of our
      combined analyses of 16S rRNA and ribosomal protein gene sequences seemed to
      adequately reflect the levels of chromosomal homology determined by DNA-DNA
      hybridization assays. On the basis of unique RFLP profiles, we identified new,
      previously unclassified group I phytoplasma strains, including the organisms that
      are associated with Ipomoea obscura witches'-broom [subgroup 16SrI-F(rr-rp)],
      maize bushy stunt [subgroup 16SrI-I(rr-rp)], and Mexican periwinkle virescence
      [subgroup 16SrI-J(rr-rp)], and new, previously unclassified group III phytoplasma
      strains, including the organism that is associated with pecan bunch [subgroup
      16SrIII-H(rr-rp)]. On the basis of the results of our analyses of 16S rRNA and
      ribosomal protein conserved gene sequences, we recognized 9 group I subgroups and
      eight group III subgroups. We propose that phytoplasma strains belonging to each
      group I and III subgroup should be distinguished taxonomically at a level
      equivalent to the subspecies level.

PMID- 8573524
TI  - Two coryneform bacteria isolated from the surface of French Gruyere and Beaufort
      cheeses are new species of the genus Brachybacterium: Brachybacterium
      alimentarium sp. nov. and Brachybacterium tyrofermentans sp. nov.
AB  - New species names, Brachybacterium alimentarium and Brachybacterium
      tyrofermentans, are proposed for two coryneform bacteria isolated from the
      surfaces of Gruyere and Beaufort cheeses. These two species are similar in their
      biochemical and chemotaxonomic characteristics but distinct from previously
      described bacteria. The most distinctive characteristics are the presence of meso
      diaminopimelic acid-containing peptidoglycan with a D-Glu-D-Asp interpeptide
      bridge and the presence of erythritol teichoic acids that contain
      diaminoglucuronic acid (an uncommon substituent). The menaquinone pattern of
      these organisms is unique among coryneform bacteria. DNA-DNA hybridization
      experiments revealed that the level of hybridization between the two organisms is
      15%, which indicates that they are distinct species. Despite the unique
      biochemical characteristics of these bacteria, a 16S rRNA sequence comparison
      revealed that they are unquestionably related to Brachybacterium faecium,
      Brachybacterium nesterenkovii, and Brachybacterium conglomeratum. DNA-DNA
      hybridization experiments performed with these three species, B. alimentarium,
      and B. tyrofermentans revealed that the levels of complementarity ranged from 11
      to 38%, values that are similar to the values obtained for Brachybacterium
      strains described previously. With the inclusion of B. alimentarium and B.
      tyrofermentans the genus Brachybacterium becomes somewhat heterogeneous with
      respect to chemotaxonomic characteristics.

PMID- 8573525
TI  - Agromyces mediolanus sp. nov., nom. rev., comb. nov., a species for
      "Corynebacterium mediolanum" Mamoli 1939 and for some aniline-assimilating
      bacteria which contain 2,4-diaminobutyric acid in the cell wall peptidoglycan.
AB  - In the course of identifying aniline-assimilating bacteria, researchers found
      some gram-positive strains that contain 2,4-diaminobutyric acid in their cell
      wall peptidoglycans and menaquinone 12 as the predominant menaquinone.
      "Corynebacterium mediolanum" and "Flavobacterium dehydrogenans" also are known to
      contain 2,4-diaminobutyric acid in their cell walls, as well as menaquinone 12,
      but the taxonomic position of these organisms has not been established
      previously. We found that the aniline-assimilating strains, together with "C.
      mediolanum" and "F. dehydrogenans," belong to a single species of the genus
      Agromyces, as determined by phenotypic characteristics, DNA-DNA relatedness data,
      and 16S ribosomal DNA sequence similarity data. The name Agromyces mediolanus sp.
      nov., nom. rev., comb. nov., is proposed for these organisms. The type strain of
      A. mediolanus is strain JCM 3346 (= ATCC 14004 = NCIMB 7206).

PMID- 8573526
TI  - Phylogenetic relationships of the filamentous sulfur bacterium Thiothrix ramosa
      based on 16S rRNA sequence analysis.
AB  - The phylogeny of Thiothrix ramosa based on 16S rRNA sequences was determined.
      This species is the first species in this genus that has been shown to be capable
      of autotrophic growth with reduced sulfur compounds as sole energy sources. T.
      ramosa forms a monophyletic clade with Thiothrix nivea, as determined by
      distance, parsimony, and maximum-likelihood methods. Both of these species
      clearly belong to the gamma subdivision of the Proteobacteria, where they are
      loosely associated with other sulfur-oxidizing chemoautotrophic organisms.

PMID- 8573527
TI  - Treatment strategies for patients with relapsed or refractory Hodgkin's disease.

PMID- 8573528
TI  - Is surgery necessary with multimodality treatment of oesophageal cancer.

PMID- 8573529
TI  - Endobronchial treatment modalities in thoracic oncology.

PMID- 8573530
TI  - Third International Symposium on recent advances in hematopoietic stem cell
      transplantation. Clinical progress, new technologies and gene therapy, March 16
      18, 1995, San Diego, CA.

PMID- 8573531
TI  - Screening for cancer, 1995: an update.

PMID- 8573532
TI  - The MINE regimen as intensive salvage chemotherapy for relapsed and refractory
      Hodgkin's disease.
AB  - BACKGROUND: Relapsed or refractory Hodgkin's disease (HD) patients were treated
      with an intensive salvage regimen (MINE) prior to high-dose therapy (HDT) with
      hematopoietic stem cell support. PATIENTS AND METHODS: One hundred HD patients
      who either failed to respond to a front-line chemotherapy regimen (induction
      failure, n = 41) or relapsed (untreated relapse, n = 54; resistant relapse, n =
      5) were treated with the MINE regimen. Each course of MINE comprised mitoguazone
      500 mg/m2 on days 1 and 5, ifosfamide 1500 mg/m2/d from day 1 to day 5,
      vinorelbine (Navelbine) 15 mg/m2 on days 1 and 5, and etoposide 150 mg/m2/d from
      day 1 to day 3. At least two courses were given at 4-week intervals. Then, 72
      patients received HDT followed by hematopoietic stem cell support. RESULTS: After
      MINE salvage, 34 patients achieved a complete response (CR) and 39 a partial
      response, yielding an overall response rate of 75%. Patients with untreated
      relapse had a 92.5% response rate and those with resistant relapse or induction
      failure a 53% response rate. A total of 58 patients reached a CR at the end of
      all treatments; 12 of them relapsed. Sixty-six patients were alive with a median
      follow-up of 26 months, including 46 patients in CR. The 2-year survival rate for
      the entire group was 59%. By univariate analysis, patients with an interval
      between their last treatment and salvage longer than 12 months, untreated
      relapse, or good performance status at salvage are shown to have longer
      survivals. The main toxic effects were neutropenia, thrombocytopenia, and
      infectious episodes. Three patients died of MINE-related complications and three
      after HDT. CONCLUSION: Given early in the course of progressive HD, the MINE
      regimen reduced tumor burden in a high proportion of patients with relapsed or
      refractory disease. Responding patients further intensified with HDT have a
      better outcome than those who have not responded to salvage treatment.

PMID- 8573533
TI  - Combined chemotherapy and radiotherapy, followed or not by surgery, in squamous
      cell carcinoma of the esophagus.
AB  - BACKGROUND: This study was designed to evaluate the feasibility of a neo-adjuvant
      combined chemo-radiotherapy in patients with localized squamous cell carcinoma of
      the esophagus. PATIENTS AND METHODS: Forty-two patients with squamous cell
      carcinoma of the esophagus, stages II and III (or stage I if considered to be
      poor candidates for immediate curative surgery), age less than 70 years and WHO
      performance status 0 to 2, were enrolled in a study of radiotherapy combined with
      chemotherapy, consisting of 2 (operated patients) or 3 (nonoperated patients)
      courses of cisplatin, vindesine, mitomycin-C or cisplatin, vinblastine. Surgery
      was routinely proposed to patients. RESULTS: Thirty-seven patients (88%) received
      full preoperative therapy. Of 30 patients responding to this preoperative
      therapy, 12 had a third cycle of treatment and 15 had esophagectomy. Three of the
      operated patients had no pathological evidence of residual tumour. Median
      survival of all 42 patients is 11 months and the 2-year survival rate is 29%.
      There is no difference in survival among responding operated or non-operated
      patients. Our group represents 95% of all eligible cases of squamous cell
      carcinoma of the esophagus occurring in Geneva during the study period.
      CONCLUSION: Our series gives a realistic view of the median survival of a
      population of patients eligible for neo-adjuvant therapy of esophagus cancer, and
      suggests that secondary surgery might not improve the patient survival.
      Furthermore, non-selected patients are at high risk for therapy-related death.

PMID- 8573534
TI  - Nodular type of lymphocyte predominant Hodgkin's disease. A clinical study of 50
      cases.
AB  - BACKGROUND: Lymphocyte predominant Hodgkin's disease (LP-HD), particularly that
      with a nodular pattern has been suggested to constitute a distinct disorder
      within the spectrum of Hodgkin's disease, this issue being based on clinical,
      morphological and immunological observations. Furthermore, the nodular LP-HD (N
      LP-HD) has been considered to differ from the diffuse subtype (D-LP-HD), although
      the data are conflicting. The question addressed in this study was whether the
      clinical course of N-LP-HD differs from that of the D-LP-HD as well as the other
      subtypes of Hodgkin's disease. PATIENTS AND METHODS: 90 cases diagnosed as LP-HD
      at St. Bartholomew's Hospital (SBH) were reviewed. The histopathological
      classification was based on the original Lukes and Butler criteria for classical
      N-LP-HD. Clinical data were retrieved from case notes and a computer database.
      Stage was determined by the Ann Arbor criteria. Survival and remission duration
      analyses were performed for the group of patients with N-LP-HD and compared with
      an histological control group of patients with the other subtypes of Hodgkin's
      disease and the cases of LP-HD that have been reclassified. RESULTS: 1. 50/90
      cases (56%) originally diagnosed as N-LP-HD qualified as N-LP-HD. No case with
      the diffuse subtype, could be identified. Twenty-three percent of the cases were
      reclassified as Mixed Cellularity and 11% as Nodular Sclerosis HD, whilst 10% as
      non-Hodgkin's lymphomas. 2. The majority of cases (78%) presented with early
      stage (I + II). Bone marrow and liver involvement were rare. 3. 92% of cases
      achieved complete remission. Recurrence developed in only 6/46 patients within 5
      12 years. A second complete remission was achieved in 5/6 (83%) cases. Further
      recurrences have not yet occurred. 4. The overall survival of the 50 cases with N
      LP-HD was 92% at 4 years and did not differ significantly from the 40 cases that
      have been reclassified. Remission duration however, was significantly better for
      the group of N-LP-HD being 81% at 12 years. 5. Second malignancies were common
      and developed in 6/50 cases (12%) with N-LP-HD within 10-15 years. These
      included: ALL (1 case), high grade B-NHL (2 cases), squamous cell carcinoma (1
      case), glioma (1 case), lung carcinoma (1 case). 6. 12/50 patients died within a
      period of follow-up, up to 21 years. 1/3 of the deaths was attributed to the
      development of second malignancy. CONCLUSIONS: The diffuse variant of LP-HD is
      rare, having not been seen at St. Bartholomew's Hospital during this time period.
      The 50 cases with N-LP-HD showed a favourable course with presentation at an
      early stage, good response to treatment, late recurrences and remission duration
      other than the other subtypes of HD. The latter could be attributable to the
      early stage at presentation of N-LP-HD, since the remission duration on a
      matching on stage analysis was superficially better in favour of N-LP-HD (p =
      0.06). The indolent course of the disease in combination with the risk of second
      malignancy cases raises the question whether histology should be taken into
      consideration in the development of new protocols for HD.

PMID- 8573535
TI  - Cyclin D1 protein expression in mantle cell lymphoma.
AB  - BACKGROUND: The t(11;14)(q13;q32) is a chromosomal abnormality usually associated
      with mantle cell (centrocytic) lymphomas, although it has occasionally been
      reported in other chronic lymphoproliferative disorders such as chronic
      lymphocytic leukemia, prolymphocytic leukemia, splenic lymphoma with villous
      lymphocytes, and multiple myeloma. This abnormality results in the translocation
      of the bcl-1 oncogene from chromosome 11 to the immunoglobulin heavy chain locus
      on chromosome 14. The bcl-1 oncogene is a member of the cyclin gene family, and
      high levels of cyclin D1 mRNA are consistently found in malignant B cell
      proliferations with t(11;14). PATIENTS AND METHODS: We examined cyclin D1 protein
      expression in 33 patients with low grade lymphoproliferative disorders and 2
      patients with reactive hyperplasias by Western blot analysis using a polyclonal
      antibody. RESULTS: 8/11 mantle cell lymphomas, 0/11 chronic lymphocytic
      leukemias, 0/4 hairy cell leukemias, 0/2 Sezary syndrome, 0/2 monocytoid B-cell
      lymphomas, 0/3 follicular lymphomas, and 0/2 reactive hyperplasias had
      overexpression of cyclin D1. Cytogenetic analysis was performed in four cases of
      mantle cell lymphoma; three of these cases had the t(11;14), one of which was
      hypotetraploid with two copies of t(11;14). Immunophenotypically, all cases of
      mantle cell lymphoma and chronic lymphocytic leukemia had coexpression of CD5 and
      CD20. CONCLUSION: Mantle cell lymphoma may be difficult to discriminate from
      chronic lymphocytic leukemia, a more indolent disease, on morphologic and
      immunophenotypic grounds. Our findings suggest that analysis of cyclin D1 protein
      expression may be helpful in differentiating mantle cell lymphomas from other low
      grade lymphoproliferative disorders.

PMID- 8573536
TI  - Central nervous system metastases in patients with ovarian carcinoma. A report of
      23 cases and a literature review.
AB  - BACKGROUND: Central nervous system (CNS) involvement by ovarian carcinoma is
      rare. PATIENTS AND METHODS: From September 1982 to September 1994, 23 patients
      with CNS metastases from ovarian carcinoma were observed in our institution.
      RESULTS: Their median age at the time of CNS metastasis diagnosis was 59 years,
      and the median interval between diagnosis of ovarian cancer and documentation of
      the metastasis was 35 months. The most common symptoms related to CNS involvement
      were motor weakness, headache, seizures, dizziness and visual disturbances. One
      patient had meningeal carcinomatosis; 22 had parenchymal lesions (18 cerebral and
      4 cerebellar). Nine patients had a single CNS lesion, and 13 had multiple
      metastatic sites. CNS was the only site of disease in 9 patients, while 8 had
      concomitant extraperitoneal dissemination. The median survival (MS) from
      diagnosis of cerebral metastases for the entire series was five months. Four
      patients were not treated (MS 3 months); 14 received radiotherapy (MS 5.5
      months), and five underwent surgical resection of solitary metastases followed by
      radiotherapy (MS 17 months). Number of CNS lesions, extent of the disease at the
      time of CNS metastasis and treatment were the only factors which significantly
      affected survival CONCLUSIONS: The prognosis of patients with CNS metastasis from
      ovarian carcinoma appears poor. However, early diagnosis followed by multimodal
      treatment may result in significant palliation and improve overall survival in a
      selected group of patients.

PMID- 8573537
TI  - Assessment of 'quality of life' using a daily diary card in a randomised trial of
      chemotherapy in small-cell lung cancer.
AB  - BACKGROUND: Quality of life (QOL) was assessed using a daily diary-card within a
      multicentre randomised trial of treatment of small-cell lung cancer. The trial
      compared a weekly dose-intensive regimen with a 3-weekly conventional treatment
      in good prognosis patients, that is patients with limited disease or extensive
      disease with a good performance status (ECOG 0or 1) and alkaline phosphatase of
      less than one and a half times the upper limit of normal. The trial which has
      been previously reported detected no difference in response or survival. PATIENTS
      AND METHODS: Daily diary cards (DDCs) were collected for up to eight months from
      the first day of chemotherapy in a cohort of 75 patients at one centre.
      Percentages of scores over a specified level were calculated for each of the
      eight diary card questions and comparisons were made between treatment arms.
      RESULTS: During the period of chemotherapy compliance in completing DDCs was
      72.5% in the weekly arm and 77.2% in the 3 weekly. Significantly worse scores
      were reported with weekly chemotherapy during this period for six of the eight
      parameters, namely: ;nausea, vomiting, happiness, appetite, general well-being
      and sleep. Recognised problems of QOL data collection, in particular, compliance,
      attrition and generalisability are highlighted by this study and are discussed in
      the paper. CONCLUSIONS: The QOL measurements indicate that 3 weekly chemotherapy
      is the preferred treatment. This study demonstrates that QOL measurements may be
      helpful in choosing between treatment alternatives where no difference in outcome
      is observed.

PMID- 8573538
TI  - The prognostic value of CEA, beta HCG, AFP, CA125, CA19-9 and C-erb B-2, beta HCG
      immunohistochemistry in advanced colorectal cancer.
AB  - BACKGROUND: Evaluation of the prognostic significance of a group of tumour
      markers and their ability to predict response to chemotherapy may allow better
      targeting of palliative treatment in advanced colorectal cancer. PATIENTS AND
      METHODS: Using a prospectively acquired database of 377 patients (pts) with
      advanced colorectal adenocarcinoma, the prognostic significance of serum CEA (342
      pts), beta HCG (203 pts), AFP (208 pts), CA125 (150 pts), CA-19-9 (76 pts) as
      well as C-erb B-2 (197 pts). Serum markers were taken prior to 5-FU based
      chemotherapy and immunohistochemistry was performed on diagnostic samples
      RESULTS: Tumour markers of poor prognostic significance in the univariate
      analysis were CEA > or = 5 micrograms/l (p = 0.006; median survival (MS 59 weeks
      vs 38 weeks) and CA125 > or = 35 U/ml (p = 0.01 MS 51 weeks vs. 30 weeks). Tumour
      markers elevated at greater than 10 times the normal value which correlated with
      a poor prognosis were CEA (p = 0.001; MS 47 weeks vs. 35 weeks), Serum beta HCG
      (p < 0.0001; MS 44 weeks vs. 7 weeks) and CA125 (p < 0.0001; MS 38 weeks vs. 15
      weeks). Poor performance status ( > 2) and poorly differentiated tumour histology
      were also correlated to poor survival. In the multivariate analysis, tumour
      markers of independent poor prognosis were CEA > or = 5 micrograms/l (Hazard
      Ratio (HR) 1.8; 95% Confidence Internal (CI) 2.8-1.2), CEA > or = 50 micrograms/l
      (HR 1.6; CI 2.1-1.2), CA125 > or = 35 U/ml (HR 1.5; CI 2.3-1.0), CA 125 > or =
      350 U/ml (HR 5.0; CI 9.6-2.6) and serum BHCG > or = 0 IU/l (HR 11.7; CI 30-4.5).
      Poor performance status (HR 6.7-5.0) and poorly differentiated histology (HR 2.8
      1.0) were the other important factors in the model. No pretreatment tumour marker
      correlated with response to chemotherapy. CONCLUSIONS: This is the largest
      prognostic study of each tumour marker in advanced disease and it clarifies
      previous conflicting reports. Serum AFP, CA19-9 and immunohistochemical stains
      beta HCG and C-erb B-2 have no prognostic significance. Serum CEA, beta HCG,
      CA125 in advanced colorectal cancer prior to chemotherapy do convey an
      independent poor prognosis which may reflect not just tumour burden but
      aggressive biology.

PMID- 8573539
TI  - Sensitivity and cellular response to different anticancer agents of a human
      ovarian cancer cell line expressing wild-type, mutated or no p53.
AB  - BACKGROUND: The cytotoxicity and gene expression induced by anticancer drugs with
      different mechanisms of action was tested in clones from a human ovarian cancer
      cell line expressing no p53, mutated p53 or wild type (wt) p53. MATERIALS AND
      METHODS: We used clones from SKOV3 cells transfected with a temperature-sensitive
      mutant p53 which expresses mutated p53 at 37 degrees C and a wild type-like p53
      at 32 degrees C. Cytotoxicity and expression of p53-related genes (WAF1 and
      GADD45) were tested after 24 hours of treatment with different drugs. RESULTS:
      All of the drugs were equally active in the different systems, independently of
      the presence of p53, with the exception of doxorubicin which was less cytotoxic
      in cells expressing a wtp53. An increase in the transcription of WAF1 and GADD45
      genes was found in cells expressing p53 and treated with the drugs. GADD45 and
      WAF1 expression was also found in cells not expressing p53 but treated with the
      drugs, suggesting that these genes can also be activated by DNA damage through a
      pathway independent of p53. A highly DNA-sequence-specific alkylator,
      tallimustine (FCE 24517), which causes a very small number of DNA lesions, does
      not increase the expression of these genes. Cyclin D1 gene expression was not
      changed after treatment with the drugs tested in cells both expressing and not
      expressing wtp53. CONCLUSIONS: Our data suggest that p53 expression does not play
      a role in increasing the susceptibility of cells not undergoing apoptosis after
      DNA damage, but that, at least in the case of doxorubicin, it can enhance the
      repair systems and reduce the cytotoxicity.

PMID- 8573540
TI  - Pharmacokinetics, metabolism, tissue and tumour distribution of the neuropeptide
      growth factor antagonist [Arg6, D-Trp7,9, NmePhe8]- substance P(6-11) in nude
      mice bearing the H69 small-cell lung cancer xenograft.
AB  - BACKGROUND: [Arg6, D-Trp7,9, NmePhe8]-Substance P (6-11) (codenamed antagonist G)
      represents the first board spectrum antagonist of a number of neuropeptides shown
      to act as growth factors in small-cell lung cancer (SCLC) and is shortly to enter
      clinical trials. DESIGN: Pharmacokinetics, metabolism, tissue disposition have
      been studied in mice (nu/nu) bearing the NCI-H69 human SCLC xenograft after
      systemic drug adminstration at an active dose (45 mg/kg i.p.). RESULTS: The
      peptide exhibited relatively long half life (28.9 min; clearance 45.6 ml/min/kg)
      and distributed widely (volume of distribution 1490 ml/kg). Marked accumulation
      of antagonist G (and its metabolites) was noted in the liver (AUC5278
      micrograms/g x min) and to a lesser extent the spleen (AUC 930 micrograms/g x
      min) but only low levels appeared to cross the blood brain barrier (AUC in brain,
      20 micrograms/g x min) or be taken up into the heart (AUC 101 micrograms/g x
      min). Tumour uptake was intermediate in value out of the 7 tissues studied (AUC
      195 micrograms/g x min). Metabolism was restricted almost exclusively to the C
      terminal of the peptide producing 4 major products: M1, deamidated antagonist G;
      M2, Harg-DTrp-NmePhe-DTrp-Leu-OH, both of which retain growth factor antagonist
      activity; M3, a combination of oxidised antagonist G [Met11(O)] and oxidised
      deamidated antagoinst G; and M4, a combination of H-Arg-DTrp-NmePhe-DTrp-OH and H
      DTrp-NmePhe-DTrp-Leu-OH. Extensive biotransformation to predominately M1 and M2
      occurred in most tissues including the tumour where the parent peptide accounted
      for only 48.5% of the total. CONCLUSION: Levels of antagonist G required to
      produce a small but significant effect on the growth of SCLC cell lines in vitro
      are in the region of 4-7 microM. Taking into account metabolites, a peak
      concentration of 4.1 microgram/g (4.3 microM) was achieved in the H69 xenograft.
      These studies reveal a favourable preclinical pharmacology profile for antagonist
      G and offer hope that anticancer activity may be achievable in man.

PMID- 8573541
TI  - Chylothorax in lymphoma: mechanisms and management.

PMID- 8573542
TI  - A phase II trial of mesna/ifosfamide, mitoxantrone and etoposide for refractory
      lymphomas.
AB  - BACKGROUND: We have previously reported that combination chemotherapy based on
      the drugs cytarabine/platinum is effective in recurring lymphomas. In this phase
      II study, we prospectively studied a combination regimen of mesna/ifosfamide,
      mitoxantrone and etoposide (MINE) in patients with recurring lymphoma who had
      already received cytarabine/platinum but did not respond to the treatment.
      PATIENTS AND METHODS: 48 patients received MINE at the following doses: mesna
      1.33 g/m2 i.v. daily x 3, and 500 mg p.o. daily 4 hours after each i.v. dose;
      ifosfamide 1.33 g/m2 i.v. daily, given concurrently with mesna, x 3 d;
      mitoxantrone 8 mg/m2 i.v. on day 1; and etoposide 65 mg/m2 i.v. daily x 3.
      Treatment cycles were 21-28 days apart, depending on patients' blood counts, with
      a maximum number of 6 cycles in responding patients. The histologic grade of the
      lymphomas according to the Working Formulation was low in 8 patients and
      intermediate in 40 patients. In the latter group, 12 were transformed from low
      grade. RESULTS: Overall, 48% of the patients responded, with 21% having a
      complete response (CR), and 27% having a partial response (PR). The median
      survival time was 9 months, and the median follow-up of survivors is 51 months at
      this writing. Median time to treatment failure was 12 months for patients with
      complete responses, and 5 months for patients with partial responses. The most
      serious complication was myelosuppression, with 2 deaths resulting from
      neutropenic infection. CONCLUSION: The MINE regimen induced responses in a
      moderate fraction of patients after their prior exposure to cytarabine/platinum
      salvage therapy, indicating there is no absolute cross resistance between these
      drug regimens.

PMID- 8573543
TI  - Phase II study of a short course of weekly high-dose cisplatin combined with long
      term oral etoposide in pleural mesothelioma.
AB  - BACKGROUND: In a previous phase II study with a dose-intensive weekly cisplatin
      schedule for six cycles, we observed a partial response in 5 of 14 patients with
      pleural mesothelioma. However, response duration was short (median 6 months).
      Since oral etoposide may theoretically be synergistic to cisplatin, we performed
      a phase II study with the combination of both drugs. PATIENTS AND METHODS: Twenty
      five chemo-naive patients with pleural mesothelioma were treated with cisplatin
      70 mg/m2 days 1-8-15 and days 29-36-43 in combination with oral etoposide 50 mg
      days 1-15 and days 29-43. Patients with stable disease, or better, continued
      treatment with oral etoposide 50 mg/m2/day days 1-21 every 28 days RESULTS All
      patients were evaluable for response and toxicity. Complete response was observed
      in one patient and partial responses in 5 patients (RR% 24%; 95% Cl: 10%-45%) for
      a median duration of 30 weeks. Twelve patients had stable disease. The response
      status never improved during maintenance treatment with oral etoposide. Most
      patients tolerated the regimen very well. Toxicity was manly haematologic with
      leukocytopenia causing treatment delays in 8 patients. Ototoxicity grade 1 or 2
      was observed in 8 patients, neurotoxicity grade 1 in 9 patients and
      nephrotoxicity grade 1 in 1 patient. CONCLUSION: Frequently administered
      cisplatin in combination with oral etoposide has a moderate but definite activity
      in pleural mesothelioma.

PMID- 8573544
TI  - Guillain Barre syndrome, a possible side effect of buffy coat transfusion and IFN
      alpha therapy in relapsed CML after bone marrow transplantation.

PMID- 8573545
TI  - Primary leiomyosarcoma of the fallopian tube.

PMID- 8573546
TI  - Lymphoma classification: R.E.A.L. or T.R.U.E. Revised European-American
      classification of lymphoid neoplasms. Taxonomy-related uncertainties are
      eliminated.

PMID- 8573547
TI  - Renin inhibition.
AB  - Modification of the renin-angiotensin-aldosterone system by renin inhibitors may
      be an alternative to angiotensin-converting enzyme inhibitors in the treatment of
      cardiovascular disease. The development of clinically useful renin inhibitors has
      been hampered by a variety of pharmacologic problems, most notably the poor oral
      bioavailability of these peptide-related compounds. Peptidomimetic renin
      inhibitors that have been stabilized to enzymatic degradation in conjunction with
      optimizing physical characteristics amenable to intestinal absorption offer the
      greatest promise to date. Studies in animal models demonstrate that renin
      inhibitors are capable of reducing both systolic and diastolic blood pressures
      without causing reflex tachycardia. The response appears to be sustained with
      chronic administration. The beneficial cardiovascular effects of these compounds
      have been confirmed in the few studies conducted in patients with hypertension
      and in those with congestive heart failure. Further development of renin
      inhibitors is warranted.

PMID- 8573548
TI  - Vascular selective calcium entry blockers in the treatment of cardiovascular
      disorders: focus on felodipine.
AB  - Calcium entry through L-type calcium channels is essential for contraction of
      both arterial smooth muscle and the myocardium, and is important in cardiac
      conduction. First-generation calcium entry blockers lack or have a modest degree
      of vascular selectivity and inhibit cardiac function at doses producing
      therapeutic arterial dilatation. Such agents may cause deterioration in patients
      with left ventricular dysfunction, and their combination with a beta-adrenergic
      blocker may adversely affect cardiac contractility and conduction. Development of
      newer agents has focused on obtaining a higher degree of vascular selectivity.
      Felodipine is a highly vascular selective calcium entry blocker, with a vascular
      selectivity ratio greater than 100, as shown experimentally. Isradipine and
      nicardipine are also vascularly selective calcium entry blockers. Hemodynamic
      studies in patients with hypertension, coronary artery disease, congestive heart
      failure, or in patients receiving beta-adrenergic blockade, show that felodipine
      can produce profound arteriolar dilatation without the negative effects of left
      ventricular systolic performance. Furthermore, felodipine alone or when added to
      a beta-adrenergic blocker does not interfere with cardiac conduction. The primary
      mechanism that accounts for the efficacy of dihydropyridine calcium entry
      blockers in hypertension and angina pectoris is arterial dilation, whereas
      nondihydropyridines may also derive part of their effect from inhibition of
      cardiac performance. As some of these patients, most commonly the elderly, have
      concomitant left ventricular dysfunction, it should be advantageous to avoid
      myocardial depression in the treatment of their primary disease. Preliminary
      studies in patients with heart failure indicate that felodipine and amlopidine
      may improve hemodynamics, reduce neurohormonal activation, and increase exercise
      tolerance, but final conclusions must await the randomized clinical trials now
      underway.

PMID- 8573549
TI  - Blockade of the human platelet GPIIb/IIIa receptor by a murine monoclonal
      antibody Fab fragment (7E3): potent dose-dependent inhibition of platelet
      function.
AB  - The platelet glycoprotein (GP) IIb/IIIa receptor can bind fibrinogen, von
      Willebrand factor, and other adhesive ligands; this binding is the final common
      pathway mediating platelet aggregation. The purpose of this study was to evaluate
      the safety and platelet inhibitory characteristics of the Fab fragment of the
      murine monoclonal anti-GPII/IIIa 7E3 antibody (m7E3 Fab) when administered
      intravenously as a single bolus dose, as a single and repeat bolus dose, and as a
      single bolus dose followed by continuous infusions of varying duration. Various
      dosage regimens of m7E3 Fab were studied in 74 patients with stable angina.
      Dosage regimens included single doses of m7E3 Fab from 0.1 to 0.3 mg/kg, a single
      dose of 0.20-0.30 mg/kg, and a repeat dose of 0.05 mg/kg, or a loading dose
      followed by a continuous infusion of m7E3 Fab for up to 36 hours. To assess the
      effect of m7E3 Fab on platelet function, quantitative blockade of GPIIb/IIIa
      receptors, inhibition of ex vivo platelet aggregation, and template bleeding time
      were measured in all patients. Dose-dependent inhibition of platelet function was
      evident in response to escalating bolus doses of m7E3 Fab, with maximum
      inhibition observed at 0.25-0.30 mg/kg body weight; at the 0.30 mg/kg dose, mean
      (+/- SE) GPIIb/IIIa receptor blockade was 81 +/- 3%, ex vivo platelet aggregation
      in response to 20 microM ADP was 14 +/- 6% of baseline, and the median bleeding
      time was > 20 minutes. Although platelet function gradually recovered following a
      single bolus injection, platelet inhibition could be sustained by continuous, low
      dose infusion of the antibody. Platelet inhibition occurred within minutes, but
      m7E3 Fab that did not bind to platelets cleared rapidly from circulation. Sixteen
      percent of the m7E3 Fab-injected subjects exhibited low titer, human anti-murine
      antibody responses. No significant bleeding or allergic reactions were observed
      in any patients. One of the 74 patients developed transient thrombocytopenia soon
      after receiving m7E3 Fab. These studies establish that m7E3 Fab can be
      administered safely at doses that cause profound inhibition of platelet function.

PMID- 8573550
TI  - Changes in serum lipoprotein(a) in hyperlipidemic subjects undergoing long-term
      treatment with lipid-lowering drugs.
AB  - Though the exact physiology and pathology of lipoprotein(a) [Lp(a)] remains
      unknown, it has been demonstrated that increased serum Lp(a) levels are
      correlated with an increased risk of atherosclerotic vascular disease. The
      effects of lipid-lowering drugs on Lp(a) levels is unclear because of
      inconsistencies between study designs. This study analyzes the effects of the
      commonly used lipid-lowering drugs pravastatin (PRAV), lovastatin (LOV), and
      cholestyramine (CHOL) on serum Lp(a) and other serum lipid levels in a parallel
      study design. Hyperlipidemic men (n = 32) were enrolled from three centers and
      treated for 48 weeks in a multicenter clinical trial using PRAV, LOV, CHOL, or a
      placebo (for the first 16 weeks only). Baseline serum low-density lipoproteins
      (LDL-C), high-density lipoproteins (HDL-C), and triglycerides were 199 +/- 38, 40
      +/- 9, and 160 +/- 70 mg/dl, respectively. At the end of 48 weeks, serum plasma
      LDL-C declined in patients randomized to PRAV, LOV, and CHOL, respectively, by
      31%, 29%, and 23% (all p < 0.001); HDL increased by 4%, 11%, and 11% (all p <
      0.001); and TG changed by -16%, -28%, and +43% (all p < 0.001). Subjects in PRAV
      and LOV changed Lp(a) by 9% and 3%, respectively. Although there was an initial
      Lp(a) decline in the first 8 weeks of CHOL therapy (p < 0.05, ANOVA), this
      returned to baseline after 48 weeks. In this parallel study design PRAV, LOV, and
      CHOL are effective LDL-lowering medications with minimal effects on plasma Lp(a).

PMID- 8573551
TI  - Pharmacodynamics and pharmacokinetics of clentiazem and diltiazem in closed-chest
      anesthetized dogs.
AB  - In the present study we investigated the relationship between pharmacodynamic and
      pharmacokinetic properties of the benzothiazepine-like calcium antagonists,
      clentiazem and diltiazem. Experiments were carried out in closed-chest
      anesthetized dogs, instrumented for hemodynamic recording and blood sampling.
      Clentiazem and diltiazem bolus injections (400 micrograms/kg) were administered
      intravenously, and subgroups of animals were sacrificed at 15, 30, 60, or 120
      minutes Clentiazem and diltiazem plasma and myocardial levels were determined by
      high performance liquid chromatography (HPLC). Clentiazem elicited a more marked
      reduction in mean arterial pressure (-17% for clentiazem vs. -12% for diltiazem),
      along with an attenuation of the expected positive reflex chronotropic response.
      Pharmacokinetic analysis revealed that clentiazem had a greater volume of
      distribution (33 +/- 16 l vs. 15 +/- 9 l for diltiazem), while the half-life of
      elimination (t1/2 beta) was similar (55 +/- 21 minutes vs. 59 +/- 23 minutes).
      The kinetic disposition profile of both drugs was analyzed through
      myocardial/plasma concentration ratios. In the distribution phase (0-15 minutes),
      this ratio was similar (26 +/- 2 for clentiazem vs. 18 +/- 5 diltiazem),
      suggesting that the myocardium was not a preferential site of distribution for
      either drugs. Data collected within the elimination phase indicate significant
      myocardial retention for clentiazem; at the end of the study period, the
      myocardial/plasma concentration ratio was twofold higher for clentiazem. The
      observed retention of clentiazem in the myocardium may be responsible for
      attenuation of the baroreflex. Clentiazem increased potency was confirmed by the
      fact that its hypotensive and cardioinhibitory effects were observed at lower
      plasma concentrations.

PMID- 8573552
TI  - Angiotensin II receptor antagonists in heart failure: rationale and design of the
      evaluation of losartan in the elderly (ELITE) trial.
AB  - Angiotensin-converting enzyme inhibitors (ACE-I) have been proven to be effective
      in reducing morbidity and mortality in patients with heart failure or post
      myocardial infarction left ventricular dysfunction. Despite evidence from several
      large-scale randomized trials, the use of ACE-I in patients with heart failure
      remains relatively low. In part, the failure to achieve more widespread use of
      ACE-I in patients with heart failure may be due to physician's perceptions of the
      side effects associated with ACE-I, such as angioedema, renal dysfunction, cough,
      and hypotension. Many of these side effects are thought to be due to ACE-I
      induced bradykinin accumulation. It is possible to inhibit the effect of
      angiotensin II without increasing bradykinin levels using an angiotensin II type
      I blocking agent such as losartan. How effective losartan is compared with an ACE
      I is uncertain, however. Some of the beneficial effects of ACE-I have been
      attributed to bradykinin accumulation, and therefore ACE-I might have an
      advantage compared with an angiotensin II type I receptor antagonist such as
      losartan. On the other hand, angiotensin II may be produced by non-ACE-I
      dependent mechanisms, which would suggest that an angiotensin II type I receptor
      blocking agent would be advantageous. To determine the relative safety and
      efficacy of an ACE-I, which results in bradykinin accumulation and inhibitors of
      angiotensin II, versus an angiotensin II type I receptor blocking agent, which
      does not result in bradykinin accumulation, we have begun the Evaluation of
      Losartan In The Elderly (ELITE) trial, which will compare the safety and efficacy
      of captopril and losartan in elderly patients with heart failure.

PMID- 8573553
TI  - Experimental rat model representing both acute and chronic heart failure related
      to autoimmune myocarditis.
AB  - The most important clinical manifestation of myocarditis is congestive heart
      failure. The precise mechanisms of heart failure during myocarditis have not been
      elucidated because no animal model that would permit in vivo study of
      hemodynamics in severe active myocarditis has been available. We monitored
      hemodynamics and left ventricular function in a rat model of experimental
      autoimmune myocarditis to determine if this model could be useful for the study
      of in vivo hemodynamics in severe active myocarditis. Lewis rats were immunized
      with human cardiac myosin suspended in complete Freund's adjuvant. Baseline
      hemodynamics were measured using an ultraminiature catheter pressure transducer
      via the right internal carotid artery, 4 weeks after immunization in one group of
      rats (acute phase) and 3 months after immunization in another group (chronic
      phase). Untreated rats served as the control group. Hemodynamic measurements were
      also obtained after infusion of dobutamine in the acute-phase and chronic-phase
      groups. The heart weight-to-body weight ratios were significantly higher in both
      the acute-phase group and the chronic-phase group compared with normal control
      rats. The baseline left ventricular systolic pressure was significantly lower in
      the chronic phase group than in the control group. Peak dP/dt and peak -dP/dt
      were significantly lower in both the acute-phase group and the chronic-phase
      group compared with the control group. Dobutamine significantly increased left
      ventricular systolic pressure, peak dP/dt, and peak -dP/dt in the chronic-phase
      group but caused only minor changes in hemodynamic variables in the acute-phase
      group. In vivo measurements of hemodynamic variables indicated the presence of
      left ventricular dysfunction in rats with experimental autoimmune myocarditis.
      This animal model may be useful for the study of both acute heart failure related
      to acute myocarditis and chronic heart failure due to diffuse myocardial
      fibrosis.

PMID- 8573554
TI  - Electrophysiological evaluation of the sodium-channel blocker carbamazepine in
      healthy human subjects.
AB  - Carbamazepine (CBZ) is a sodium-channel blocker used mainly for the treatment of
      epileptic seizures and neuralgias. It may impair the function of the cardiac
      conduction system in susceptible patients, but its electrophysiological effects
      have not been thoroughly assessed in the normal heart, which was the aim of the
      present study. Ten healthy volunteers, mean age 32 years, underwent two
      electrophysiological investigations at baseline and three at different dose
      levels of CBZ. The transesophageal atrial stimulation technique was used to
      evaluate sinus node function, refractoriness of the atrial myocardium,
      atrioventricular conduction, and ventricular depolarization and repolarization
      (as reflected by the QRS, JT, and QT intervals) at spontaneous rhythm and after
      atrial pacing. Atropine was administered to facilitate 1:1 conduction and
      assessment of rate-dependent effects. At the highest CBZ dose (800 mg/day), which
      gave plasma concentrations within the upper therapeutic range, the PQ interval
      was mildly prolonged (151 vs. 159 msec; p < 0.01). In addition, the shortening of
      the JT interval normally seen at higher pacing rates was counteracted by high
      dose CBZ, as demonstrated by a lower mean slope of the regression line after
      atropine and CBZ than after atropine alone (0.17 vs. 0.20; p < 0.05). No other
      effects were detected. At therapeutic levels CBZ had minimal effects on the
      healthy conduction system, supporting its safe use in the absence of cardiac
      disease.

PMID- 8573555
TI  - Rate-dependent anisotropic conduction property in the epicardial border zone of
      canine myocardial infarcts and its modification by moricizine.
AB  - We evaluated anisotropic conduction properties, different conduction velocities
      depending on fiber orientation, in normal and infarcted myocardium and the
      effects of moricizine on anisotropic conduction. Various cycle lengths of
      stimulation were applied to 15 mongrel dogs, and epicardial mapping was performed
      using a 96-channel mapping electrode. Moricizine was then administered to seven
      dogs and the same procedure was performed. Conduction velocities were calculated
      from these maps. Programmed electrical stimulations were performed before and
      after moricizine administration to induce ventricular arrhythmias. Before
      moricizine administration, a rate-dependent decrease in longitudinal conduction
      velocity was observed in the infarcted zone. Moricizine suppressed longitudinal
      conduction in the normal zone significantly at 300 msec pacing, but not at slower
      rates. Moricizine at a dose of 4 mg/kg, on the other hand, suppressed
      longitudinal conduction in the infarcted zone significantly at all pacing cycle
      lengths. The effect of moricizine on transverse conduction was inconsistent. In
      three dogs, sustained ventricular tachycardia (VT) was induced either before or
      after moricizine administration. The mean cycle length of sustained VT was
      prolonged from 202 msec to 291 msec after 4 mg/kg of moricizine. Thus, the
      changes in cycle length of ventricular tachycardia observed were most likely the
      result of slowing of conduction velocity, especially in the longitudinal
      direction, in the infarcted myocardium. We conclude that the electrophysiologic
      nature of the subacute ischemic model was modified by moricizine, leading to
      depression of the conduction velocity of longitudinal conduction and the
      inducibility of ventricular arrhythmias.

PMID- 8573556
TI  - Digoxin and increased mortality among patients recovering from acute myocardial
      infarction: importance of digoxin dose. The SPRINT Study Group.
AB  - Digoxin therapy has been suggested to increase mortality risk in survivors of
      acute myocardial infarction. Since digoxin is a drug with a narrow
      therapeutic/toxic ratio, we raised the hypothesis that the association between
      digoxin and post myocardial infarction mortality may have a dose-dependent
      relationship. The purpose of this study was to evaluate this hypothesis. We
      retrospectively analyzed data from 1731 survivors of acute myocardial infarction.
      At the time of hospital discharge, 175 patients (10%) were taking digoxin. The
      exact dosage of digoxin was ascertained in 153 (87%) patients. Patients were
      divided into two groups based on the weekly dosage of digoxin at hospital
      discharge: The first group included 41 patients who were treated with a low dose
      (< or = 1.5 mg per week, usually 0.125 mg daily). The second group included 112
      patients treated with a full dose (> 1.5 mg per week, usually 0.25 mg daily).
      Both groups were comparable with regard to mean age, gender, history of prior
      myocardial infarction, diabetes mellitus, hypertension, and prior angina. There
      were no significant differences in the incidence of in-hospital complications,
      such as heart failure, atrial fibrillation, ventricular tachycardia, ventricular
      fibrillation, and postinfarction angina. One year mortality was significantly
      higher among patients treated with a full dose [19 of 112 (17%)] than patients
      treated with a low dose of digoxin [1 of 41 (2%); p < 0.02] Multivariate analysis
      performed by the Cox proportional hazards model identified treatment with a full
      dose of digoxin as an independent determinant associated with increased death
      during the first year after myocardial infarction (hazard ratio 10.7; 95%
      confidence interval 1.4-80.5). Thus, mortality among myocardial infarction
      survivors treated with digoxin was related to a full-dose therapy. Patients
      treated with a low dose experienced a low mortality rate. Our findings raise
      concern that digoxin may exert a dose-dependent deleterious effect upon the
      survival of patients recovering from acute myocardial infarction.

PMID- 8573557
TI  - Effects of myelin or cell body brainstem lesions on 3-channel Lissajous'
      trajectories of fast and slow components of feline auditory brainstem evoked
      potentials.
AB  - Auditory brainstem evoked potentials (ABEP) were recorded from 16 awake cats
      using three orthogonal differential electrode pairs before and during a week
      after inducing neuronal lesions localized to the cochlear nucleus (CN) or the
      superior olivary complex (SOC), or myelin lesions localized to the fibers of the
      trapezoid body. ABEPs were digitally filtered to include only the slow
      ('pedestal') component, or only the faster first to fifth components, and three
      channel Lissajous' trajectories (3CLTs) of these fast and slow components of ABEP
      were obtained. Cell body lesions and myelin lesions induced effects on 3CLT
      measures of both fast and slow components of ABEP. The results suggest a primary
      contribution of cell body activity to the slow component, and a primary fiber
      tract contribution to the fast components. However, the results do not support
      exclusive generation of the pedestal by cell body and dendritic post-synaptic
      potentials and of the faster components by action potentials along fibers. The
      results are consistent with a set of generators for each of the slow and fast
      components of ABEP, consisting of both cell bodies and their output fibers, that
      are spatially distributed in the brainstem.

PMID- 8573558
TI  - ABR interpeak latencies in rats are shorter at low click intensities.
AB  - There are conflicting findings concerning whether auditory nerve-brainstem evoked
      response (ABR) interpeak latencies (e.g. brainstem transmission time - BTT) are
      constant in response to different stimulus intensities. In order to study the
      effects of click intensity on the BTT, and to try to determine the mechanism of
      such an effect, ABR was recorded from 10 adult white Sabra rats in response to
      different click intensities. The stimulus intensity was reduced from the highest
      intensity generated by the equipment until no responses could be obtained. Band
      reject (notched) noise was presented simultaneously with the clicks in order to
      restrict the region of basilar membrane activation. BTT decreased with decreasing
      click intensity and this was accompanied by a prolongation of the latency of wave
      I to a greater extent than that of wave IV. At high and intermediate intensities,
      wave I appeared as two split peaks. These effects were not abolished by the
      restricting notched noise. Possible mechanisms of these latency changes are
      considered.

PMID- 8573559
TI  - Auditory brainstem response in obstructive sleep apnea patients.
AB  - Auditory brainstem responses (ABR) were recorded in 79 patients diagnosed as
      suffering from obstructive sleep apnea (OSA). The patients were divided into
      three subgroups (mild, moderate and severe) according to the severity of the
      syndrome. A statistically significant prolongation was found in the latency
      values of waves I, III and V in all three subgroups, compared to a control group
      of 29 healthy subjects. The transmission time between waves I and III and I and V
      was found to be prolonged in the moderate and severe OSA subgroups, compared to
      the control group. However, from a clinical point of view only 10% (eight
      patients) of the OSA group showed a clinically significant prolongation in their
      ABR latency values compared to the norms (mean +/- 2SD) of the specific ABR
      recording system used in this study. In addition, 36 of the OSA group underwent
      uvulopalato-pharyngoplasty (UPPP). There were no statistically significant
      differences in the ABR recording preoperatively versus post-operatively.

PMID- 8573560
TI  - Lateralization and discrimination of dichotic clicks: evidence from patients with
      brainstem lesions and normal cohorts.
AB  - The ability to lateralize and discriminate dichotic clicks was tested in multiple
      sclerosis patients with normal audiograms and in normal cohorts. Lateral position
      spread over a greater range with interaural level differences than with
      interaural time differences, and was related to the two asymmetries by different
      functions. Measures of binaural acuity were inversely related to the slopes of
      the two functions. One group of patients performed normally with both types of
      interaural asymmetry, another group performed normally only with level
      differences; a third group of patients could not perform normally with either.

PMID- 8573561
TI  - Auditory event related potentials in simulated tinnitus.
AB  - It was previously demonstrated that noise induced tinnitus (NIT) patients have
      prolonged reaction times and event related potentials (ERPs) that are reduced in
      amplitude and prolonged in latency. This study considered whether these
      alterations occurred as a consequence of the competing auditory tinnitus
      sensation or as a result of a possible cognitive processing dysfunction in NIT
      patients. ERPs and reaction times (RTs) were recorded in response to a standard
      oddball auditory target detection paradigm, with and without simulated tinnitus.
      Tinnitus was simulated using a high tone narrow band noise presented at the
      forehead via a standard audiometric bone vibrator. The subjects consisted of 19
      males suffering from noise induced hearing loss without tinnitus. The latencies
      and amplitudes of the ERP components N1, P2, N2, and P3, as recorded along the
      midline scalp sites (Fz, Cz, and Pz) and bilateral temporal sites (C3 and C4),
      did not differ significantly when recorded with and without simulated tinnitus.
      Similarly, the associated reaction times did not differ significantly. These
      findings suggest that the ERP alterations previously reported to exist for NIT
      patients cannot be explained simply as a consequence of increased task difficulty
      and cognitive loading due to the tinnitus sound.

PMID- 8573562
TI  - Functional development of auditory sensitivity in the fetus and neonate.
AB  - The human fetus responds to sound stimuli while still in utero. The rat and cat
      begin to hear only after birth. Therefore neonatal rat and cat are used as models
      of the development of auditory sensitivity in the human fetus. The inner ear of
      rat responds to stimuli delivered directly to it (bone conduction) before the
      middle ear can conduct sounds to the inner ear. During this period, middle ear
      development involves mesenchyme resorption, ossicular hardening and opening of
      the external canal. The latter stages of inner ear development involve increased
      magnitude of the endocochlear potential which augments cochlear transduction and
      the active cochlear amplifier. These developmental stages are probably controlled
      by thyroid hormone which activates several genes leading to the synthesis of
      proteins and enzymes required for the structural and functional maturation of the
      ear. This likely includes the Na+,K(+)-ATPase of the stria vascularis which
      generates the endocochlear potential. The magnitude of the endocochlear potential
      is dependent on oxygen supply so that the human fetus in utero whose blood
      carries less oxygen than the newborn has a hypoxia-induced sensorineural hearing
      loss. Upon birth and transition from placental to pulmonary oxygenation, the
      oxygen content of blood is increased, the magnitude of the endocochlear potential
      is elevated and auditory sensitivity is enhanced.

PMID- 8573563
TI  - Spectral and kinetic studies on the activation of soluble guanylate cyclase by
      nitric oxide.
AB  - The soluble form of guanylate cyclase (sGC) is the only definitive receptor for
      the signaling agent nitric oxide (.NO). The enzyme is a heterodimer of homologous
      subunits in which each subunit binds 1 equiv of 5-coordinate high-spin heme. .NO
      increases the Vmax of sGC up to 400-fold and has previously been shown to bind to
      the heme to form a 5-coordinate complex. Using stopped-flow spectrophotometry, it
      is demonstrated that the binding of .NO to the heme of sGC is a complex process.
      .NO first binds to the heme to form a 6-coordinate nitrosyl complex, which then
      converts to a 5-coordinate nitrosyl complex through one of two ways. For 28 +/-
      4% of the heme, the 6-coordinate nitrosyl complex rapidly (approximately 20 s-1)
      converts to the 5-coordinate complex. For the remaining 72 +/- 4% of the heme,
      the conversion of the 6-coordinate nitrosyl complex to a 5-coordinate nitrosyl
      complex is slow (0.1-1.0 s-1) and is dependent upon the interaction of .NO with
      an unidentified non-heme site on the protein. The heme (200 nM) was completely
      converted to the 5-coordinate state with as little as 500 nM .NO, and the
      equilibrium dissociation constant of .NO for activating the enzyme was determined
      to be < or = 250 nM. Gel-filtration analysis indicates that the binding of .NO to
      the heme has no effect on the native molecular mass of the protein. Correlation
      of electronic absorption spectra with activity measurements indicates that the 5
      coordinate nitrosyl form of the enzyme is activated relative to the resting 5
      coordinate ferrous form of the enzyme.

PMID- 8573564
TI  - Functional immobilization of a DNA-binding protein at a membrane interface via
      histidine tag and synthetic chelator lipids.
AB  - The coupling of a DNA-binding protein to self-organized lipid monolayers is
      examined at the air-water interface by means of film balance techniques and
      epifluorescence microscopy. We used two recombinant species of the heat shock
      factor HSF24 which differ only in a carboxy-terminal histidine tag that interacts
      specifically with the nickel-chelating head group of a synthetic chelator lipid.
      As key function, HSF24 binds to DNA that contains heat-shock responsible promoter
      elements. In solution, DNA-protein complex formation is demonstrated for the wild
      type and fusion protein. Substantial questions of these studies are whether
      protein function is affected after adsorption to lipid layers and whether a
      specific docking via histidine tag to the chelator lipid leads to functional
      immobilization. Using lipid mixtures that allow a lateral organization of
      chelator lipids within the lipid film, specific binding and unspecific adsorption
      can be distinguished by pattern formation of DNA-protein complexes. At the lipid
      interface, functional DNA-protein complexes are only detected, when the histidine
      tagged protein was immobilized specifically to a chelator lipid containing
      monolayer. These results demonstrate that the immobilization of histidine-tagged
      biomolecules to membranes via chelator lipids is a promising approach to achieve
      a highly defined deposition of these molecules at an interface maintaining their
      function.

PMID- 8573565
TI  - Influence of GC and AT specific DNA minor groove binding drugs on intermolecular
      triplex formation in the human c-Ki-ras promoter.
AB  - We have used DNase I footprinting and gel shift assays to characterize the
      interaction of DNA binding drugs mithramycin, distamycin, and berenil with an
      intermolecular triplex formed by the human c-Ki-ras promoter. A purine-rich
      triplex-forming oligonucleotide (ODN) forms a stable intermolecular triple helix
      (triplex) with a homopurine (PR):homopyrimidine (PY) motif in the human c-Ki-ras
      promoter which contains a 22bp PR:PY region (-328 to -307). This triplex
      structure is comprised of 15 G.G:C triplets interspersed with 7 T.A:T triplets.
      Mithramycin binding sites in the human c-Ki-ras promoter encompass most of the
      triplex target site and three G-C-rich sequences downstream of this triplex
      forming region. Mithramycin binding within the c-Ki-ras promoter completely
      abrogates triplex formation. Furthermore, the addition of mithramycin to pre
      formed triplex by c-Ki-ras promoter displaces the major groove bound ODN. Five
      prominent distamycin binding sites are noted within the c-Ki-ras promoter
      including the triplex-forming site as well as A-T-rich regions upstream and
      downstream of the triplex site. Berenil does not bind within the triplex target
      sequence, and only one berenil binding sequence downstream of the triplex motif
      was present within the c-Ki-ras promoter fragment. Neither distamycin nor berenil
      prevents triplex formation, and, furthermore, the addition of either distamycin
      or berenil to the pre-formed triplex structure did not displace the major-groove
      bound third strand. This study demonstrates that GC-specific and AT-specific
      minor groove ligands differentially affect the intermolecular pur.pur:pyr
      triplex. A possible biological significance of mithramycin interaction with
      intramolecular triplex is discussed.

PMID- 8573566
TI  - The electrostatic contribution to the B to Z transition of DNA.
AB  - In this paper, the finite difference nonlinear Poisson-Boltzmann (NLPB) equation
      is used to calculate the electrostatic contribution to the B to Z transition of
      DNA using detailed molecular structures of each DNA form. The electrostatic
      transition free energy is described as a balance between the change in
      intramolecular Coulombic interactions and charge-dependent interactions between
      the DNA and the solvent. As in many prior studies, we find that the larger
      electrostatic repulsions among the more closely spaced Z-DNA phosphates
      destabilize this form compared to B-DNA in the absence of solvent. However, as a
      result of the more compact three-dimensional geometry of Z-DNA, both water and
      salt are found to strongly stabilize this conformation to the extent that the
      total electrostatic free energy favors the B to Z transition in aqueous solution.
      Water acts not only by screening the inter-phosphate repulsions but also by
      solvating both charged and polar groups on Z-DNA more favorably than B-DNA. In
      addition, Z-DNA is stabilized by a substantially higher concentration of nearby
      counterions than B-DNA. The relative stabilization of Z-DNA by salt increases
      with increasing bulk salt concentration, leading to the high-salt B to Z
      transition. We find that the salt dependence of the B to Z transition free energy
      calculated with the NLPB equation agrees reasonably well with experimental
      results. Since electrostatic interactions are found to favor the Z-form,
      nonelectrostatic forces must be responsible for the relative stability of B-DNA
      in solution. An analysis of these forces suggests that the conformational entropy
      may play an important role.

PMID- 8573567
TI  - Distal cavity fluctuations in myoglobin: protein motion and ligand diffusion.
AB  - Experimentally, distal mutations in myoglobin substantially affect the
      contribution of fast and slow phases to picosecond geminate recombination of NO
      following flash photolysis. Earlier simulations of ligand diffusion among distal
      pocket mutants showed greatly differing rates of collisions between the ligands
      and the heme iron, suggesting that distal residues affect recombination by
      controlling ligand access to the iron [Gibson, Q. H., Regan, R., Elber, R.,
      Olson, J. S., & Carver, T. (1992) J. Biol. Chem. 267, 22022-22034). In this work,
      molecular dynamics simulations of sperm whale myoglobin and mutations at
      positions 68 (E11) and 107 (G8) have been examined to investigate the structural
      mechanism that controls ligand diffusion and iron accessibility. Visualization of
      the distal ligand-accessible spaces shows a pattern of cavities (common to other
      hemoglobins and myoglobins) that fluctuate and interconnect due to protein
      motions. Access to the iron atom is highly sensitive to these fluctuations in the
      native structure, perhaps a reason for the strong conservation of distal
      residues. The positions of the helices surrounding the distal heme site were
      monitored to assess the involvement of more collective protein motions in ligand
      diffusion. Ligand migrations and collisions with the iron appear related to
      expansion of the distal protein matrix due to helix movements. The helices
      surrounding the distal site also make relative adjustments on the order of 0.5 A
      to accommodate the presence of a mobile diatomic ligand, suggesting a mechanism
      for communication between the heme site and the exterior of the protein.

PMID- 8573568
TI  - Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide.
AB  - Diphtheria toxin (DT), a 58 kDa protein secreted by lysogenic strains of
      Corynebacterium diphtheriae, causes the disease diphtheria in humans by gaining
      entry into the cytoplasm of cells and inhibiting protein synthesis. Specifically,
      the catalytic (C) domain of DT transfers the ADP-ribose group of NAD to
      elongation factor-2 (EF-2), rendering EF-2 inactive. In order to investigate how
      the C-domain of DT binds NAD and catalyzes the ADP-ribosylation of EF-2, the
      crystal structure of DT in complex with NAD has been determined to 2.3 A
      resolution. This is the first crystal structure of an ADP-ribosyltransferase (ADP
      RT) enzyme in complex with NAD and suggests the features of the ADP-RT fold which
      are important for NAD binding. The conformation of NAD in the complex and the
      proximity of the Glu148 carboxylate group of the C-domain to the scissile, N
      glycosidic bond of NAD suggest plausible modes of catalysis of the ADP
      ribosylation reaction. Residues 39-46 of the active-site loop of the C-domain
      become disordered upon NAD binding, suggesting a potential role for this loop in
      the recognition of the ADP-ribose acceptor substrate, EF-2. The negatively
      charged phosphates and two ribose hydroxyls of NAD are not in direct contact with
      any atoms of the C-domain. Instead, they form an exposed surface which appears to
      be presented for recognition by EF-2. Structural alignments of the DT-NAD complex
      with the structures of other members of the ADP-RT family suggest how NAD may
      bind to these other enzymes.

PMID- 8573569
TI  - Cooperativity in the binding of echinomycin to DNA fragments containing closely
      spaced CpG sites.
AB  - Quantitative footprinting has been used to investigate cooperative binding of the
      antitumor antibiotic echinomycin to DNA fragments containing closely spaced CpG
      steps. The sequences of the designed DNA fragments contained two pairs of strong
      echinomycin binding sites: a pair of ACGT sites together with an ACGT site and a
      TCGA site, either directly adjacent or separated by two or four A.T base pairs.
      The results demonstrate that the binding of echinomycin to the sequences ACGTACGT
      and TCGAACGT is highly cooperative. The extent of cooperativity depends on the
      nature of the sequences clamped by the antibiotic and diminishes as the distance
      between the binding sites is increased. Various methods of extracting the
      information necessary to establish cooperativity have been compared. Beyond the
      specific interest in echinomycin-DNA interaction, the present quantitative
      footprinting study provides a model that may be generally applicable for
      designing investigations into cooperativity in drug-DNA recognition.

PMID- 8573570
TI  - Mode of selectivity in cyclic AMP receptor protein-dependent promoters in
      Escherichia coli.
AB  - Escherichia coli cAMP receptor protein (CRP) controls more than 20 genes. There
      are significant differences in the promoter regions in these genes. Thus, an
      elucidation of the mechanism of CRP action requires knowledge about the mode of
      selectivity in these promoters. An earlier study [Heyduk, T., & Lee, J. C. (1990)
      Proc. Natl. Acad. Sci. U.S.A. 81, 1744-8] indicates that the CRP(cAMP)1 conformer
      exhibits the highest affinity for the lac PI site in the lac operon. It is
      conceivable that the CRP conformer that binds with the highest affinity to these
      other sites may not be CRP(cAMP)1. To investigate this possibility, the binding
      of CRP to nine CRP binding sites was studied as a function of cAMP concentration.
      The CRP binding sites employed in this investigation were chosen to represent the
      primary promoter sites from class I (lac site PI) and class II (sites PI of gal
      and crp) as well as secondary CRP binding sites (crp site PII and cat PII) to
      further understand the molecular mechanism of CRP in controlling the
      transcription of these bacterial genes. The affinity of CRP for three synthetic
      CRP binding sites was also examined to explore the contribution of the inverted
      repeat region and sequences surrounding the recognition motifs. The synthetic
      sequences are gallac which contains the lac recognition motifs in the background
      of gal, modified cat PII which contains an 8-base pair spacer between the
      recognition motifs rather than the 7-base pair sequence naturally found in cat
      PII, and a random sequence that has no known similarity to any CRP binding site
      found in nature. The apparent affinities of these sequences for CRP were
      quantitatively determined to be biphasic in their cAMP dependence. The CRP(cAMP)1
      conformer was found to have the highest affinity for all of the DNA sequences
      examined. No specific affinity was observed for these sequences with free CRP and
      CRP(cAMP)2. The affinity of CRP for DNA was sequence-dependent and increased in
      the following order: random < cat site PII, modified cat site PII, crp sites PI
      and PII < gal site PI < lac site PI < gallac. These results indicate that the
      entire CRP binding site sequence and its natural variability provide information
      to CRP. These promoter sites which appear to have different mechanisms at the
      molecular level are transcriptionally controlled by the same CRP conformer,
      CRP(cAMP)1. Thus, the regulation of transcription by CRP is more subtle than
      choosing different conformational forms of CRP. Using "physiological"
      concentrations of various components, a computer simulation study was conducted
      to illustrate the possible consequences of the thermodynamic parameters
      determined in this study. It is evident that the promoters of protein systems
      regulating the transport and metabolism of carbohydrates are responsive to low
      cAMP concentrations. However, the promoter for controlling the expression of CRP
      is highly regulated by the fluctuation of cAMP concentration.

PMID- 8573571
TI  - Pressure-induced perturbation of apomyoglobin structure: fluorescence studies on
      native and acidic compact forms.
AB  - The nature of the structural changes that apomyoglobin undergoes when subjected
      to hydrostatic pressure, ranging from atmospheric pressure to 2.4 kbar, has been
      investigated by steady-state fluorescence and frequency domain fluorometry. In
      particular, we have examined the intrinsic tryptophanyl emission and that of the
      extrinsic probe 1-anilino-8-naphthalenesulfonate (ANS) bound to apomyoglobin at
      neutral pH, as well as at strongly acidic high-salt conditions. Apomyoglobin at
      neutral pH undergoes a pressure-induced structural transition, which causes the
      disorganization of the heme binding region with a consequent ANS dissociation; a
      concomitant increase in solvent accessibility to the N-terminus of the
      macromolecule in which tryptophans are located is also observed. At 2.4 kbar, the
      tryptophanyl emission is not coincident with that of a fully solvent exposed
      residue, thus suggesting that the N-terminal region of the apomyoglobin molecule
      retains elements of organized structure. The spectroscopic properties of the
      structural state attained at 2.4 kbar and neutral pH are different from those of
      the acidic compact state. The acidic compact state of apomyoglobin undergoes a
      pressure-induced structural change that brings the tryptophanyl residues in
      contact with the solvent, but does not affect the ability to bind ANS.

PMID- 8573572
TI  - Accurate kinetic modeling of alkaline phosphatase in the Escherichia coli
      periplasm: implications for enzyme properties and substrate diffusion.
AB  - Alkaline phosphatase in the periplasm of Escherichia coli presents many of the
      complex factors that may influence enzymes in vivo. These include an environment
      that contains a high enzyme concentration, is densely populated with other
      macromolecules, and is separated from other compartments by a partial diffusion
      barrier. A previous study provided a partial description of this situation and
      developed a model that utilized kinetic behavior to estimate the permeability of
      the outer membrane [Martinez, M. B., et al., (1992) Biochemistry 31, 11500]. This
      study extends that description to provide a complete model for the enzyme at all
      substrate levels. Some of the parameters needed for complete modeling include the
      following: outer membrane permeability to the substrate and product, catalytic
      efficiency of the enzyme, number of enzymes per cell, and effects of the reaction
      product (an inhibitor) on the enzyme. The theoretical model fit the data quite
      well over a wide range of values for each of these parameters. The best fit of
      theory with experimental data required that the rate constant for product escape
      from the periplasm was 4-fold greater than that for substrate entry. This
      correlated with the relative sizes of the substrate and product. The excellent
      fit of theory and results suggested that alkaline phosphatase and its substrate
      were unaffected by the solution conditions in the periplasm. That is, the
      catalytic parameters (kcat and KM), determined for the enzyme in dilute solution,
      appeared to be unchanged by the conditions in the periplasm. The major factor
      that altered the kinetic behavior was the combined effect of the permeability
      barrier and the dense population of enzyme molecules in the periplasm. Given the
      large impact of these parameters on reaction properties, the excellent fit of
      theory and results was striking. Overall, this study demonstrated that enzyme
      action in the complex biological environment can be accurately modeled, if all
      factors that influence enzyme behavior are known.

PMID- 8573573
TI  - Interactions of intercalative and minor groove binding ligands with triplex
      poly(dA).[poly(dT)]2 and with duplex poly(dA).poly(dT) and poly[d(A-T)]2 studied
      by CD, LD, and normal absorption.
AB  - The binding of 9-aminoacridine and one bis-acridine compound to double helical
      poly(dA).poly-(dT) and poly[d(A-T)]2 and triple helical poly(dA).[poly(dT)]2 has
      been investigated using linear dichroism (LD) and circular dichroism (CD). A
      close examination of the negative reduced LD and the induced CD for the first pi-
      >pi* transition absorption region leads us to conclude that the acridine moiety
      of the 9-aminoacridine and bis-acridine molecule intercalates with both duplex
      and triplex DNA. Binding geometries of the acridine moieties in the examined
      polynucleotides are similar to those found for the ligands with DNA (Hansen et
      al. (1984) J. Chem. Soc., Chem. Commun., 509-511). It is also found that both 9
      aminoacridine and bis-acridine effectively enhance the thermal stability of the
      triplex DNA. The corresponding spectra for the complexes of the minor groove
      binders DAPI and Hoechst with poly-(dA).[poly(dT)]2 were studied for comparison.
      They both show a positive LD and a mixing ratio dependent positive CD in the
      ligand absorption region, similar to those of their duplex complexes. This
      indicates that these ligands bind in the grooves of the triplex, probably to the
      one corresponding to the minor groove of the template duplex.

PMID- 8573574
TI  - Glycine-15 in the bend between two alpha-helices can explain the thermostability
      of DNA binding protein HU from Bacillus stearothermophilus.
AB  - On the basis of sequence comparison of thermophilic and mesophilic DNA binding
      protein HUs, Bacillus stearothermophilus DNA binding protein HU (BstHU) seems to
      gain thermostability with a change in amino acid residues present on the
      molecular surface. To evaluate the contribution of exchange of each amino acid to
      the thermostability of BstHU, we constructed three mutants, BstHU-T13A (Thr13 to
      Ala), BstHU-G15E (Gly15 to Glu), and BstHU-T33L (Thr33 to Leu), in which the
      amino acids in BstHU were changed to the corresponding ones in Bacillus subtilis
      DNA binding protein HU (BsuHU). Stability of the mutant proteins was determined
      from thermal-denaturation curves. Replacement of Gly15 located in the turn region
      between alpha 1 and alpha 2 helices (HTH motif), with Glu (BstHU-G15E), resulted
      in a decrease in thermostability, and the Tm value was 54.0 degrees C compared to
      the Tm value of 63.9 degrees C for BstHU. The mutants, BstHU-T13A and BstHU-T33L,
      were, by contrast, slightly more stable (Tm values of 67.0 and 65.6 degrees C for
      BstHU-T13A and BstHU-T33L, respectively) than the wild type. We then generated
      the BsuHU mutant protein BsuHU-E15G, where Glu15 in BsuHU was in turn replaced by
      Gly, and we analyzed the thermostability. This substitution clearly enhanced the
      melting temperature by 11.8 degrees C (Tm value: 60.4 degrees C for BsuHU-E15G)
      compared to the value for BsuHU (Tm: 48.6 degrees C). Thus, Gly15 in the HTH
      motif of BstHU has an important role in the thermostability of BstHU.
      Characterization of the structure of the BstHU-G15E by 1H-NMR analysis showed
      that solvent accessibility of amide proton of Ala21 in the mutant was
      significantly increased compared with that of wild type, which means that the
      structure of the HTH motif in the N-terminal region in the mutant was changed to
      a more open conformation, thereby avoiding the interaction of Ala21 with either
      Ser17 by hydrogen bond or Ala11 by hydrophobic interaction.

PMID- 8573575
TI  - Exocyclic amine of the conserved G.U pair at the cleavage site of the Tetrahymena
      ribozyme contributes to 5'-splice site selection and transition state
      stabilization.
AB  - A phylogenetically conserved guanine.uracil (G.U) pair defines the 5'-exon/intron
      boundary of precursor RNAs containing group I introns. In this wobble base pair,
      the G forms two hydrogen bonds with U in a base pairing geometry shifted from
      that of a canonical Watson-Crick pair. On the basis of thermodynamic measurements
      of synthetic base pair analogs (inosine, diaminopurine riboside, guanosine, or
      adenosine paired with U, C, or isocytidine) in place of the G.U pair, we have
      previously reported that the N2 exocyclic amine of the G is important for docking
      the 5'-exon into the active site of the Tetrahymena ribozyme [Strobel, S. A., &
      Cech, T. R. (1995) Science 267, 675-679]. Here we describe kinetic
      characterization of ribozyme-substrate combinations containing the same series of
      analogs. By measuring the rate constants of 5'-exon miscleavage (cleavage at
      incorrect phosphates), we demonstrate that the 5'-exon/intron boundary is
      primarily defined by the exocyclic amine of the G. The amine makes its
      contribution (2.5 kcal.mol-1) in the context of all three wobble pairs tested but
      fails to make a significant contribution (< 0.8 kcal.mol-1) when presented in a
      Watson-Crick base pairing geometry. We also demonstrate that the exocyclic amine
      makes a modest contribution to chemical transition state stabilization (1.0
      kcal.mol-1 relative to an inosine-U pair). The majority of this transition state
      contribution (0.7 kcal.mol-1) is independent of that contributed by the 2'
      hydroxyl of the neighboring U. This argues against the model in which substantial
      transition state stabilization is derived from a water molecule bridging between
      the exocyclic amine of G and the 2'-hydroxyl of U. Instead it suggests that the
      tertiary interaction between the exocyclic amine and its hydrogen bonding partner
      in the active site is slightly improved during the chemical transition. We
      conclude that the exocyclic amine of G is the primary contributor to many
      characteristics of reactivity that have been ascribed to the conserved G.U pair,
      including stabilization of the chemical transition state and definition of the 5'
      exon/intron boundary.

PMID- 8573576
TI  - Proteins C1 and C2 of heterogeneous nuclear ribonucleoprotein complexes bind RNA
      in a highly cooperative fashion: support for their contiguous deposition on pre
      mRNA during transcription.
AB  - Proteins C1 and C2 together comprise about one-third the protein mass of
      mammalian core 40S heterogeneous nuclear ribonucleoprotein particles (40S hnRNP)
      and exist as heterotetramers of (C1)3C2. On the basis of nonequilibrium binding
      studies, it has been suggested that the C proteins specifically bind oligo(U)-
      and poly(U)-rich sequences, and preferentially associate with uridine-rich
      regions near the 3' termini of many introns. We describe here a more quantitative
      characterization of the equilibrium binding properties of native and recombinant
      C protein to homoribopolymers using fluorescence spectroscopy. Like C protein
      from HeLa cells, the recombinant proteins spontaneously oligomerize to form
      tetramers with the same hydrodynamic properties as native protein. Near
      stoichiometric binding titrations of the fluorescent homoribopolymer
      polyethenoadenosine (poly[r(epsilon A)]) with recombinant (C1)4 and (C2)4
      homotetramers along with competition binding assays with poly(A) and poly(C)
      indicate that the binding site size (n) is between 150 and 230 nucleotides. This
      site size range is in close agreement with that previously determined for native
      C protein through hydrodynamic and ultrastructural studies (approximately 230
      nucleotides). (C1)4 and (C2)4 bind poly(G) with intrinsic affinities (Ki) of
      10(9) M-1, which are a hundredfold higher than their affinities for poly(U). In
      opposition to reports that C protein does not bind poly(A) and poly(C), we find
      that the C proteins bind these substrates with moderate Ki, but with high
      cooperativity (omega). The overall affinity (K omega) for the binding of both
      proteins to poly(A) and poly(C) is 10-fold higher (> 10(8) but < 10(9) M-1) than
      their affinities for poly(U). The highly cooperative binding of C protein to
      these substrates provides a mechanistic basis for the distribution of C protein
      along the length of nucleic acid substrates.

PMID- 8573577
TI  - Lack of correlation between Sendai virus P/C mRNA structure and its utilization
      of two AUG start sites from alternate reading frames: implications for viral
      bicistronic mRNAs.
AB  - The polycistronic P/C mRNA of Sendai virus encodes five proteins (C', P, C, Y1,
      and Y2) each of which initiates from a distinct start site. Two major proteins, P
      and C, are expressed in approximately equimolar amounts from two consecutive AUGs
      in overlapping reading frames. To better understand the mechanism of expression
      of the C protein from a downstream AUG, site-directed mutants of the P/C mRNA
      were created and expressed in COS1 cells. The secondary structure of the mRNA was
      examined to determine whether the mRNA structure played any role in the synthesis
      of the C protein. Our results ruled out any significant involvement of the 5'
      UTR, sequence contexts, secondary structure, distance between the start sites,
      and sequences downstream to the C-AUG. However, they are consistent with the
      concept that the synthesis of the C protein is primarily dependent on the
      orientation of its reading frame, i.e., +1 in relation to the upstream P reading
      frame. The downstream reading frame was translated poorly when it occurred in +2
      orientation in relation to the upstream reading frame. Interestingly, all the
      known functional bicistronic mRNAs with overlapping reading frames from
      cytoplasmic RNA viruses have their downstream reading frame in +1 orientation
      relative to the upstream frame. We propose that the evolutionary conservation of
      the downstream reading frame in +1 orientation in these bicistronic mRNAs is
      important for its efficient translation.

PMID- 8573578
TI  - Thermodynamics of the membrane insertion process of the M13 procoat protein, a
      lipid bilayer traversing protein containing a leader sequence.
AB  - For the first time, the standard free energy change, delta Gzero, of a membrane
      inserting protein with a leader sequence has been determined experimentally,
      using M13 procoat protein as an example. The partition coefficient for the
      distribution of the procoat protein between the aqueous phase and the membrane
      phase of preformed lipid vesicles yielded a value of gamma = 6.5 x 10(5) M-1,
      corresponding to a delta Gzero of -10.4 kcal/mol, based on measurements of the
      fluorescence energy transfer between the intrinsic tryptophan of the protein and
      a suitably labeled lipid membrane of POPC. For comparison, the partition
      coefficient of the M13 coat protein between the aqueous and the POPC lipid
      bilayer phase was determined to be distinctly lower: gamma = 1 x 10(5) M-1 (delta
      Gzero = -9.3 kcal/mol). Proteinase K digestion experiments have been performed,
      showing that 20% of the procoat protein bound to lipid vesicles spontaneously
      integrate in a transbilayer form, whereas 80% remain inserted in the interfacial
      membrane region. By taking together these results, an upper limit for the free
      energy change of the transmembrane insertion of procoat protein was estimated to
      be -14.8 kcal/mol. In order to distinguish further the contribution arising from
      insertion of the procoat protein into the membrane interfacial region from that
      due to transmembrane insertion, the partition coefficient of the mutant procoat
      protein OM30R [which contains a positively charged amino acid in its mature
      hydrophobic segment (exchange of a Val to an Arg residue at position 30)] was
      determined, yielding gamma = 0.3 x 10(5) M-1 (delta Gzero = -8.6 kcal/mol).
      Previously reported in vivo experiments have shown that the OM30R mutant protein
      is not translocated across Escherichia coli membranes but only binds to the inner
      surface. The results presented here indicate that although the insertion of the
      procoat protein into the interfacial region of the lipid bilayer contributes the
      major part to delta Gzero, it is the final energy gain of the interaction of the
      hydrophobic portions of the folded pre-protein with the lipid chains which drives
      the transmembrane insertion of the M13 procoat protein. Neither the leader
      sequence nor the mature coat protein alone yields this free energy gain. For the
      different proteins investigated here, spontaneous membrane insertion occurs only
      for fluid lipid bilayers, but not for membranes in the crystalline lipid phase.
      Furthermore, by using lipid bilayers with negative membrane surface charges, it
      was shown that both procoat and coat proteins are electrostatically attracted to
      the surface of the lipid membrane, though only to a small extent, with apparent
      partition coefficients of the same order of magnitude as for the
      phosphatidylcholine lipid membrane.

PMID- 8573580
TI  - Structural dynamics in the plastocyanin-photosystem 1 electron-transfer complex
      as revealed by mutant studies.
AB  - A series of plastocyanin mutants have been constructed by site-directed
      mutagenesis and expressed in Escherichia coli to elucidate the interaction
      between plastocyanin and photosystem 1 in the photosynthetic electron-transfer
      chain. Leu-12 has been replaced with alanine, asparagine, glutamate, and lysine,
      while Tyr-83 has been exchanged for histidine, phenylalanine, and leucine. Phe
      35, Asp-42, and Gln-88 have been mutated to tyrosine, asparagine, and glutamate,
      respectively. The mutations that have been introduced do not seem to place any
      strain on the tertiary structure according to optical absorption and electron
      paramagnetic resonance (EPR) spectroscopic studies. However, there are changes in
      the reduction potential for the Leu-12 mutants that cannot be accounted for by
      electrostatic interactions alone. For some of the mutants, the pI shifts, in
      accordance with the changes in the number of titratable groups. Only the Leu-12
      mutants show any major change in their photosystem 1 kinetics, while the mutants
      in the acidic patch show minor changes, suggesting that both the hydrophobic and
      acidic patches make contact with photosystem 1 but that the electron transfer
      occurs at the hydrophobic interface, most probably via the His-87 residue. The
      kinetics are best described with a model in which a rate-limiting conformational
      change occurs in the plastocyanin-photosystem 1 complex [Bottin, H., & Mathis, P.
      (1985) Biochemistry 24, 6453-6460; Sigfridsson, K., Hansson, O., Karlsson, B.G.,
      Baltzer L., Nordling, M., & Lundberg, L. G. (1995) Biochim. Biophys. Acta 1228,
      28-36], where the changes observed are attributed to changes in the dynamics
      within the electron-transfer complex.

PMID- 8573579
TI  - Spinach chloroplast coupling factor CF1-alpha 3 beta 3 core complex: structure,
      stability, and catalytic properties.
AB  - A minimal chloroplast coupling factor CF1 core complex, containing only alpha and
      beta subunits, has been isolated from spinach thylakoids [Avital, S., & Gromet
      Elhanan, Z. (1991) J. Biol. Chem. 266, 7067-7072]. This CF1(alpha beta) exhibited
      a low MgATPase activity, which was stimulated but not inhibited by low
      concentrations of the species-specific CF1 effector tentoxin. As is reported
      here, the structure of CF1(alpha beta) could not be determined due to its
      instability. However, its pretreatment with high tentoxin concentrations resulted
      in a remarkable 50-fold stimulation of the MgATPase activity as well as
      stabilization of its hexameric structure, thus enabling the isolation of a more
      active CF1-alpha 3 beta 3 complex by size-exclusion chromatography. A detailed
      characterization of the MgATPase activity of this tentoxin-stabilized CF1-alpha 3
      beta 3 hexamer, as compared to the activity of a CF1 complex lacking the epsilon
      subunit, revealed similar apparent Km values and a similar stimulation by the
      presence of 100 microM tentoxin in the assay medium, but drastic differences in
      all other tested assays. Most pronounced were their different temperature
      profiles and different responses to all added inhibitors and stimulators of the
      CF1 MgATPase activity and to excess free Mg2+ ions. The specific properties of
      the stable CF1-alpha 3 beta 3 hexamer are identical to those earlier reported for
      its parent-unstable CF1(alpha beta). These results indicate that, although the
      CF1 gamma subunit is not required for the low CF1(alpha beta) ATPase activity nor
      for the higher activity of the tentoxin-stabilized CF1-alpha 3 beta 3, it plays a
      central role in obtaining the typical functional properties of the CF1-ATPase.
      Kinetic cooperativity could not be critically tested as yet with any F1-alpha 3
      beta 3. However, tentoxin, as azide, has been shown to inhibit multisite but not
      unisite catalysis. Therefore, the observation that CF1-alpha 3 beta 3 is only
      stimulated by tentoxin suggests that the required presence of CF1-gamma for
      obtaining inhibition by tentoxin reflects the role of this subunit in cooperative
      interactions between the catalytic sites.

PMID- 8573581
TI  - Circular dichroism spectroscopy of monoclonal antibodies that bind a superpotent
      guanidinium sweetener ligand.
AB  - Three monoclonal antibodies (mAb) with nanomolar affinity to the superpotent
      trisubstituted guanidinium sweetener ligand N-(p-cyanophenyl)-N'
      (diphenylmethyl)guanidineacetic acid were studied by circular dichroism (CD)
      spectroscopy. Two mAb, NC6.8 (IgG2b,kappa) and NC10.8 (IgG3, kappa) exhibited
      similar CD spectra, but mAb NC10.14 (IgG2b, lambda) had very different CD spectra
      in both far- and near-UV regions. Some of these differences may be due to effects
      of aromatic amino acid side chains, especially Trp and Tyr, located at the
      immunoglobulin intradomain surfaces. Heavy- and light-chain dissociation of
      reduced Fab fragments in 1 M acetic acid minimized these effects. Ligand binding
      changed the sign and amplitudes of the near-UV CD spectra of all three mAb.
      Calculation of the CD difference spectra (bound minus free) of stoichiometrically
      bound antibody-ligand complexes allowed us to visualize the net spectral changes.
      On the basis of the three-dimensional structures experimentally solved for NC6.8
      and theoretical models of NC10.8 and NC10.14, we suggest that the p-cyanophenyl
      moiety on the sweetener ligand acts as a molecular pointer in the CD spectra and
      identifies contact aromatic residues in the different antibody binding pockets.

PMID- 8573582
TI  - Selective inhibition of N-formylpeptide-induced neutrophil activation by
      carbamate-modified peptide analogues.
AB  - Stimulation of the leukocyte N-formylpeptide receptor (FPR) induces chemotaxis,
      cell adhesion, free radical release, and degranulation, responses associated with
      infection and inflammation. Under conditions where continuous activation of the
      receptor prevails, neutrophil-dependent tissue damage ensues. Antagonists of the
      FPR have potential for use as diagnostic and therapeutic agents. Hence, we have
      synthesized and evaluated a series of amino-terminal carbamate analogues of the
      peptide Met-Leu-Phe (MLF) in order to determine the structural requirements for
      imparting agonist or antagonist activity at the human neutrophil FPR. Peptides
      were evaluated in three in vitro assays: receptor binding, superoxide anion
      release, and cell adhesion. Unbranched carbamates (methoxycarbonyl,
      ethoxycarbonyl, and n-butyloxycarbonyl) resulted in agonist activity, whereas
      branched carbamates (iso-butyloxycarbonyl, tert-butyloxycarbonyl, and
      benzyloxycarbonyl) were antagonists. The peptide antagonists were more potent
      inhibitors of superoxide anion release than cell adhesion by 4-7-fold. When iso
      butyloxycarbonyl-MLF (i-Boc-MLF) was further modified at the carboxy terminus
      with Lys, antagonist potency was retained but without functional selectivity.
      Further C-terminal modification with the radionuclide linker
      diethylenetriaminepentaacetic acid did not alter the potency of i-Boc-MLFK. These
      results indicate that the switch from agonist to antagonist activity can be
      achieved by modifying the overall size and shape of the amino-terminal group;
      that modifications at both the amino and carboxy termini can alter the functional
      selectivity of the peptide; and that modifications can be tolerated at the
      carboxy terminus to allow for development of an antagonist for diagnostic
      applications.

PMID- 8573583
TI  - The immunosuppressive metabolite of leflunomide is a potent inhibitor of human
      dihydroorotate dehydrogenase.
AB  - The active metabolite of leflunomide. A771726, is a novel immunosuppressive
      compound that has been shown to be a powerful antiproliferative agent for
      mononuclear and T-cells. The molecular mechanism of action for this compound has
      not been clearly established. In vitro cellular and enzymatic assays, however,
      demonstrate that leflunomide is an inhibitor of several protein tyrosine kinases,
      with IC50 values between 30 and 100 microM. The in vivo properties of A771726 are
      reminiscent of another immunosuppressive agent, brequinar sodium, which has been
      shown to be a nonomolar inhibitor (Ki = 10-30 nM) of the enzyme dihydroorotate
      dehydrogenase (DHODase). On the basis, we have investigated the effects of
      leflunomide and A771726 on the activity of purified recombinant human DHODase. We
      find that A771726 is a potent inhibitor of DHODase (Ki = 179 +/- 19 nM), while
      the parent compound, leflunomide, had no inhibitory effect at concentrations as
      high as 1 microM. Studies of the dependence of inhibition on the concentrations
      of the substrates ubiquinone and dihydroorotate demonstrate that A771726 is a
      competitive inhibitor of the ubiquinone binding site and is noncompetitive with
      respect to dihydroorotate. The potency of A771726 as a DHODase inhibitor is thus
      100-100-fold greater than that reported for its inhibition of protein tyrosine
      kinases. These data suggest that an alternative explanation for the
      immunosuppressive efficacy of A771726 may be the potent inhibition of DHODase by
      this compound.

PMID- 8573584
TI  - Chemical reactivity and spectroscopy of the thiol ester-linked p-coumaric acid
      chromophore in the photoactive yellow protein from Ectothiorhodospira halophila.
AB  - We have recently identified p-coumaric acid as the chromophore of the photoactive
      yellow protein (PYP) from the purple sulfur bacterium Ectothiorhodospira
      halophila, a blue-light photoreceptor with rhodopsin-like photochemistry [Hoff,
      W. D., Dux, P., Hard, K., Nugteren-Roodzant, I. M., Crielaard, W., Boelens, R.,
      Kaptein, R., Van Beeumen, J., & Hellingwerf, K. J. (1994) Biochemistry 33, 13959
      13962]. Here we report on the chemistry of the linkage of this new photoactive
      cofactor to apoPYP: (i) Analysis of chromophore-peptide conjugates of PYP by high
      resolution mass spectrometry unambiguously shows that the p-coumaric acid
      molecule is bound to Cys 69 via a thiol ester bond. The PYP chromophore is the
      first cofactor known to be stably thiol ester-linked to its apoprotein. (ii) The
      chemical reactivity of this thiol ester bond with respect to dithiothreitol,
      performic acid, and high pH is similar to that of disulfide bridges. These
      treatments result in the cleavage of the thiol ester bond, concomitant with
      strong shifts in the UV/vis absorbance band of the chromophore. (iii) The
      spectral properties of the PYP chromophore under different conditions are related
      to the structural integrity of the protein, the presence of the thiol ester bond,
      and the ionization state of the phenolic proton of the chromophore. These results
      are important for the general problem of spectral tuning in photoreceptor
      proteins.

PMID- 8573585
TI  - Binding dynamics and electron transfer between plastocyanin and photosystem I.
AB  - The mechanism of the electron transfer from the soluble protein plastocyanin to
      the multiprotein complex of photosystem I from spinach has been studied in
      detail. The two kinetic components of P700+ reduction by plastocyanin after a
      laser flash, showing a constant half-life of 11 microseconds and a variable half
      life of the second-order reaction, respectively, are used to monitor the electron
      transfer from bound and soluble plastocyanin. The effect of increasing
      concentration of reduced plastocyanin on both of these kinetic components and the
      competition by oxidized plastocyanin is used to estimate the individual
      dissociation constants of the complex between the proteins in each of its
      oxidized and reduced state. The dissociation constant of oxidized plastocyanin is
      about six times larger than that of 7 microM found for reduced plastocyanin and
      purified PSI. Consistent with this result the midpoint redox potential of
      plastocyanin bound to photosystem I either in equilibrium with soluble
      plastocyanin or after cross-linking to photosystem I is found to be 50-60 mV
      higher than that of soluble plastocyanin. It is concluded that the driving force
      of the intracomplex electron transfer is decreased in favor of an optimized
      turnover of photosystem I. Double-flash excitation shows that oxidized
      plastocyanin has to leave the complex after the electron transfer before a new
      reduced plastocyanin molecule can bind to photosystem I. This release of oxidized
      plastocyanin with a half-life of about 60 microseconds limits the turnover of
      photosystem I. All data are consistently described by a model including the
      formation of a complex at a single binding site of photosystem I. Differences in
      the rate and binding constants are discussed with respect to the structure and
      the electrostatic and hydrophobic interactions stabilizing the complex as well as
      their modification by the membrane environment in situ.

PMID- 8573586
TI  - Role of portal region lysine residues in electrostatic interactions between heart
      fatty acid binding protein and phospholipid membranes.
AB  - The structure of heart fatty acid binding protein (HFABP) is a flattened beta
      barrel comprising 10 antiparallel beta-sheets capped by two alpha-helical
      segments. The helical cap region is hypothesized to behave as a portal "lid" for
      the entry and release of ligand from the binding pocket. The transfer of fatty
      acid from HFABP is thought to occur via effective collisional interactions with
      membranes, and these interactions are enhanced when transfer is to membranes of
      net negative charge, thus implying that specific basic residues on the surface of
      HFABP may govern the transfer process [Wootan, M. G., & Storch, J. (1994) J.
      Biol. Chem. 269, 10517-10523]. To directly examine the role of charged lysine
      residues on the HFABP surface in specific interactions with membranes, chemical
      modification and selective mutagenesis of HFABP were used. All surface lysine
      residues were neutralized by acetylation of recombinant HFABP with acetic
      anhydride. In addition, seven mutant HFABPs were generated that resulted in
      charge alterations in five distinct sites of HFABP. Modification of the protein
      did not significantly alter the structural or ligand binding properties of HFABP,
      as assessed by circular dichroism, fluorescence quantum yield, and ligand binding
      analyses. By using a resonance energy transfer assay, transfer of 2-(9
      anthroyloxy)palmitate (2AP) from acetylated HFABP to membranes was significantly
      slower than transfer from native HFABP. In addition, in distinct contrast to
      transfer from native protein, the 2AP transfer rate from acetylated HFABP was not
      increased to acceptor membranes of increased negative charge. Transfer of 2AP
      from HFABP mutants involving K22, located on alpha-helix I (alpha-I) of the
      helical cap region, was 3-fold slower than transfer from wild-type protein,
      whereas rates from a mutant involving the K59 residue, located on the beta 2-turn
      of the barrel near the helical cap, were 2-fold faster than those of wild type. A
      double mutant involving K22 and K59 resulted in transfer rates identical to those
      of wild type, indicating that at least two domains are involved in determining
      the overall rate of ligand transfer. In addition, 2AP transfer rates from HFABP
      mutated at position 22 were totally unaffected by the charge characteristics of
      acceptor membranes, in marked contrast to wild type and other members of the
      mutant series. Further, by introducing a positive charge to alpha-helix II (alpha
      II) of the helical cap region, 2AP transfer rates increased by 4-fold and
      properties of HFABP transfer began to approach those seen for AFABP, another
      member of the FABP family thought to transfer ligand via collisional interactions
      with membranes, which has a lysine residue in the alpha-II helix. These studies
      demonstrate that the helical cap region of HFABP may play an important role in
      governing ionic interactions between binding protein and membranes.

PMID- 8573587
TI  - Interactions of 2-methoxyestradiol, an endogenous mammalian metabolite, with
      unpolymerized tubulin and with tubulin polymers.
AB  - 2-Methoxyestradiol (2ME) is an endogenous mammalian catabolite of estradiol with
      antimitotic activity. Although it is a competitive inhibitor of the binding of
      colchicine to tubulin, it has unusual effects on glutamate-induced tubulin
      polymerization. Polymer that was little changed in morphology assembled at a
      reduced rate and was relatively cold stable. We have now examined interactions of
      [4-3H]-2ME with unpolymerized tubulin and polymer. The [3H]2ME binds avidly to
      tubulin even on ice, and it is readily displaced by other colchicine site drugs.
      An association rate constant on ice of 1.9 x 10(2) M-1s-1 was obtained. Scatchard
      analysis indicated a single class of binding site and an association equilibrium
      constant of 5.7 x 10(5) M-1. These values lead to a calculated dissociation rate
      constant of 3.3 x 10(-4) s-1. In glutamate-induced tubulin assembly, a reaction
      that requires GTP and leads to the formation of sheets of parallel
      protofilaments, increasing amounts of [3H]2ME were incorporated into polymer,
      reaching near-stoichiometry with tubulin at 100 microM 2ME. Equivalent binding of
      [3H]2ME occurred when the drug was added to preformed polymer, but binding of
      [3H]2ME to polymer was not readily inhibited by colchicine site drugs.
      Significant amounts of [3H]2ME were also incorporated into microtubule polymer
      formed with microtubule-associated proteins, glycerol, or 4
      morpholineethanesulfonate buffer, but the stoichiometry was substantially lower
      than that in the sheet polymer induced by either glutamate or 1,4
      piperazineethanesulfonate buffer. The structural differences between the
      microtubule and sheet polymers leading to these differences in apparent affinity
      for 2ME are unknown, but presumably interaction of the estrogen metabolite with
      cellular microtubules has functional significance related to the antimitotic
      properties of the compound.

PMID- 8573588
TI  - Membrane organization at low cholesterol concentrations: a study using 7
      nitrobenz-2-oxa-1,3-diazol-4-yl-labeled cholesterol.
AB  - Cholesterol is most often found distributed nonrandomly in the plane of the
      bilayer, giving rise to cholesterol-rich and -poor domains. Many of these domains
      are thought to be crucial for the maintenance of membrane structure and function.
      However, such well-characterized domains generally occur in the membranes that
      contain relatively large amounts of cholesterol. Cholesterol organization in
      membranes containing very low amounts of cholesterol has not been investigated
      extensively. Recent evidence from differential-scanning calorimetric studies
      suggest that cholesterol may not form uniform monodisperse solutions, as assumed
      earlier, in the membranes even at very low concentrations. Fluorescent
      cholesterol analogues, when chosen carefully, offer a powerful approach for
      studying the distribution and organization of cholesterol in membranes at low
      concentrations. In this paper, we have studied the organization of cholesterol in
      membranes at very low concentrations (up to 5 mol % of the total lipid) using a
      fluorescent cholesterol analogue (NBD-cholesterol) which is labeled with the 7
      nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group at the flexible acyl chain, without
      any alteration in the structural features necessary for proper membrane
      incorporation. Our results show that NBD-cholesterol exhibits local organization
      even at very low concentrations. This is consistent with the recently suggested
      model of cholesterol organization in membranes at low concentrations, involving
      the formation of transbilayer, tail-to-tail dimers [Harris, J.S., Epps, D. E.,
      Davio, S. R., & Kezdy, F.J. (1995) Biochemistry 34, 3851-3857]. The implications
      of such local cholesterol organization in membranes that have very low
      cholesterol content in vivo, such as the endoplasmic reticulum and the inner
      mitochondrial membrane, open up interesting possibilities.

PMID- 8573589
TI  - Structural studies of mutant glucocorticoid receptor transactivation domains
      establish a link between transactivation activity in vivo and alpha-helix-forming
      potential in vitro.
AB  - We have previously shown, using circular dichroism spectroscopy, that the tau 1
      core peptide has alpha-helix-forming potential in vitro [Dahlman-Wright et al.
      (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 1699-1703]. The tau 1 core peptide is a
      58-amino acid peptide, constituting the core of the transactivation activity of
      the tau 1 major transactivation domain of the human glucocorticoid receptor
      [Dahlman-Wright et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 1619-1623].
      Further structural studies of the peptide, using NMR spectroscopy, identified
      three segments with alpha-helical character. In this report we show that reduced
      protein expression or stability is not responsible for the reduced in vivo
      transactivation potential of tau 1 core peptides with proline substitutions in
      proposed alpha-helical regions. Rather, the reduced alpha-helix propensity of the
      corresponding purified peptides in vitro suggests that alpha-helices are involved
      in the molecular mechanism of glucocorticoid receptor mediated changes in gene
      activity.

PMID- 8573590
TI  - Ubiquitination-dependent proteolysis of O6-methylguanine-DNA methyltransferase in
      human and murine tumor cells following inactivation with O6-benzylguanine or 1,3
      bis(2-chloroethyl)-1-nitrosourea.
AB  - In this study, we investigated the role of ubiquitination in the disposition of
      the inactivated O6-methylguanine-DNA methyltransferase (MGMT) protein in human
      (HT-29 and CEM) and murine (ts85) tumor cells. Using a combination of
      immunoprecipitation and immunoblotting techniques with antibodies against
      ubiquitin and MGMT, and anti-ubiquitin immunoaffinity chromatography, the MGMT
      protein was found to coexist with small amounts of its ubiquitinated species in
      both human and mouse tumor cells, suggesting the presence of endogenous
      inactivated MGMT. Further, treatment of HT-29 and CEM cells with MGMT
      inactivating compounds, O6-benzylguanine (O6-BG, 20 microM) or 1,3
      bis(chloroethyl)-1-nitrosourea (BCNU, 100 microM), resulted in increased levels
      of ubiquitinated MGMT within 1.5-3 h of drug exposure. Kinetic studies in HT-29
      cells treated with O6-BG indicated a slow and gradual conversion of the
      inactivated MGMT to its polyubiquitinated forms over a course of 3-18 h, with a
      concomitant disappearance of the parent MGMT protein. We also characterized the
      previously reported O6-BG-induced degradation of MGMT in HT-29 cell extracts
      [Pegg et al. (1991) Carcinogenesis 12, 1679-1683] and showed the extracts to be
      active in conjugation of the MGMT protein with ubiquitin. The proteolysis of O6
      BG-inactivated MGMT in HT-29 cell extracts was energy-dependent and was markedly
      stimulated by ATP and Mg2+ ions. Using the ts85 temperature-sensitive mutant cell
      line, which expresses a thermolabile ubiquitin-activating enzyme, we observed a
      differential stability of the inactivated MGMT protein at permissive and
      nonpermissive temperatures. These results provide conclusive evidence that the
      MGMT protein, following its inactivation, is degraded via the ubiquitin
      proteolytic pathway.

PMID- 8573591
TI  - Dependence of flux size and efficiency of oxidative phosphorylation on external
      osmolarity in isolated rat liver mitochondria: role of adenine nucleotide
      carrier.
AB  - The aim of this work was a thermodynamic and kinetic study of the influence of
      varying external osmolarity on overall oxidative phosphorylations in isolated rat
      liver mitochondria. When external osmolarity is increased from 100 to 400 mosM by
      using a non-penetrant sugar: (i) matrix volume diminishes, (ii) state 3
      respiratory rate decreases when state 4 slightly varies, (iii) states 3 and 4
      protonmotive force and NAD(P)H level increase, whereas oxidative phosphorylation
      efficiency (ATP/O) decreases. Indeed, respiratory flux versus protonmotive force
      relationships depend on the osmolarity considered: the lower the external
      osmolarity, the higher the span of overall driving force necessary for the same
      respiratory rate. To further investigate the mechanism of the decrease in
      respiratory and ATP synthesis flux leading to a lowering in oxidative
      phosphorylation efficiency, we determined the adenine nucleotide carrier control
      coefficient on respiratory and ATP synthesis rates respectively. The main result
      is that the adenine nucleotide carrier control coefficient on respiratory rate
      decreases, and conversely that adenine nucleotide carrier control on ATP
      synthesis rate increases, from iso- to hyperosmolarity. Furthermore, whatever the
      osmolarity, when state 3 respiratory rate is titrated with carboxyatractyloside,
      the same relationship is observed between ATP/O ratio and respiratory flux. From
      many previous studies, it has been shown that an increase in external osmolarity
      and a consequent decrease in matrix volume inhibits almost all mitochondrial
      proton pumps (coupling site 1 and 2 of respiratory chain, ATPase) in different
      ways. In this work, we show that in phosphorylating mitochondria, the adenine
      nucleotide carrier plays a key role: its inhibition as the external osmolarity
      increases lowers the state 3 respiration close to state 4 level and consequently
      leads to a decrease in oxidative phosphorylation efficiency.

PMID- 8573592
TI  - Comparison of the inhibitory action of synthetic capsaicin analogues with various
      NADH-ubiquinone oxidoreductases.
AB  - Capsaicin is a new naturally occurring inhibitor of proton-pumping NADH
      ubiquinone oxidoreductase (NDH-1), that competitively acts against ubiquinone. A
      series of capsaicin analogues was synthesized to examine the structural factors
      required for the inhibitory action and to probe the structural property of the
      ubiquinone catalytic site of various NADH-ubiquinone reductases, including non
      proton-pumping enzyme (NDH-2), from bovine heart mitochondria, potato tuber
      (Solanum tuberosum, L) mitochondria and Escherichia coli (GR 19N) plasma
      membranes. Some synthetic capsaicins were fairly potent inhibitors of each of the
      three NDH-1 compared with the potent rotenone and piericidin A. Synthetic
      capsaicin analogues inhibited all three NDH-1 activities in a competitive manner
      against an exogenous quinone. The modification both of the substitution pattern
      and of the number of methoxy groups on the benzene ring, which may be
      superimposable on the quinone ring of ubiquinone, did not drastically affect the
      inhibitory potency. In addition, alteration of the position of dipolar amide bond
      unit in the molecule and chemical modifications of this unit did not change the
      inhibitory potency, particularly with bovine heart and potato tuber NDH-1. These
      results might be explained assuming that the ubiquinone catalytic site of NDH-1
      is spacious enough to accommodate a variety of structurally different capsaicin
      analogues in a dissimilar manner. Regarding the moiety corresponding to the alkyl
      side chain, a rigid diphenyl ether structure was more inhibitory than a flexible
      alkyl chain. Structure-activity studies and molecular orbital calculations
      suggested that a bent form is the active conformation of capsaicin analogues. On
      the other hand, poor correlations between the inhibitory potencies determined
      with the three NDH-1 suggested that the structural similarity of the ubiquinone
      catalytic sites of these enzymes is rather poor. The sensitivity to the
      inhibition by synthetic capsaicins remarkably differed between NDH-1 and NDH-2,
      supporting the notion that the sensitivity against capsaicin inhibition
      correlates well with the presence of an energy coupling site in the enzyme (Yagi,
      T. (1990) Arch. Biochem. Biophys. 281, 305-311). It is noteworthy that several
      synthetic capsaicins discriminated between NDH-1 and NDH-2 much better than
      natural capsaicin.

PMID- 8573593
TI  - Effects of chloride ion substitutes and chloride channel blockers on the
      transient outward current in rat ventricular myocytes.
AB  - The Cai(2+)-insensitive transient outward current, ilo was studied at 20-24
      degrees C in rat ventricular myocytes with the whole cell recording patch-clamp
      technique. The current was recorded before and after replacement of chloride by
      methanesulfonate or aspartate or in the absence and the presence of chloride
      channel blockers, SITS or 9-anthracene carboxylic acid. In control conditions (in
      the presence of external divalent cations, Ca2+ and Cd2+, Cd2+ being used to
      suppress Ca2+ current), ilo inactivation was composed of a fast and a slow
      component. When methanesulfonate was substituted for external Cl-, the peak
      current decreased to a variable extent, but the inactivation of the remaining
      current was still composed of a fast and a slow component. In contrast, the
      inactivation of the difference current was well fitted by a single exponential.
      The time to peak of the difference current was shorter than that of the current
      recorded either in the absence or the presence of methanesulfonate. Both
      activation- and steady-state inactivation-voltage curves were either unchanged (n
      = 4) or shifted by a few mV (5.5 mV, n = 14) towards positive potentials when
      methanesulfonate was substituted for Cl-. The current remaining in
      methanesulfonate reversed at potentials closed to EK. The difference current was
      composed of a peak and a steady-state component. The peak was suppressed by 4
      aminopyridine whereas the steady-state component was not. The peak was also
      suppressed when pipette solution contained Cs+ instead of K+ but was still
      present when the Hepes concentration in both external and pipette media was
      increased 5-fold (50 mM vs. 10 mM). When aspartate was substituted for Cl- or
      when 2 mM SITS was added to the external solution (in the absence of Ca2+ and
      Cd2+ because aspartate is known to chelate Ca2+ ions and possibly other divalent
      cations), ilo was reduced to a similar extent in the two cases and the difference
      current was composed of a peak (inactivation fitted by a single exponential) and
      a steady-state component. The SITS-sensitive transient current reversed at a
      potential close to ECl. When 5 mM 9-anthracene carboxylic acid was added to
      external solution (in the presence of Ca2+ and Cd2+), the peak of the difference
      current was similar to that observed when Cl- was substituted by
      methanesulfonate. The difference current resulting from the substitution of
      methanesulfonate for chloride was not changed when the pipette solution contained
      either 50 mM EGTA (instead of 5 mM) or 10 mM EGTA and 10 mM BAPTA. The nature of
      Cs(+)- and 4-aminopyridine-sensitive transient outward current suppressed by
      chloride ion substitutes or chloride channel blockers is discussed.

PMID- 8573594
TI  - Estimation of the H+/H- ratio of the reaction catalysed by the nicotinamide
      nucleotide transhydrogenase in chromatophores from over-expressing strains of
      Rhodospirillum rubrum and in liposomes inlaid with the purified bovine enzyme.
AB  - Two strains of Rhodospirillum rubrum were constructed in which, by a gene dosage
      effect, the transhydrogenase activity of isolated chromatophores was increased 7
      10-fold and 15-20-fold, respectively. The H+/H- ratio (the ratio of protons
      translocated per hydride ion equivalent transferred from NADPH to an NAD+
      analogue, acetyl pyridine adenine dinucleotide), determined by a spectroscopic
      technique, was approximately 1.0 for chromatophores from the over-expressing
      strains, but was only approximately 0.6 for wild-type chromatophores. Highly
      coupled proteoliposomes were prepared containing purified transhydrogenase from
      beef-heart mitochondria. Using the same technique, the H+/H- ratio was close to
      1.0 for these proteoliposomes. It is suggested that the mechanistic H+/H- ratio
      is indeed unity, but that a low ratio is obtained in wild-type chromatophores
      because of inhomogeneity in the vesicle population.

PMID- 8573595
TI  - Biochemical studies of the c-type cytochromes of the sulfate reducer
      Desulfovibrio africanus. Characterization of two tetraheme cytochromes c3 with
      different specificity.
AB  - Three c-type cytochromes were isolated and characterized from the sulfate reducer
      Desulfovibrio africanus. A basic tetraheme cytochrome c3 of molecular mass 16 kDa
      was previously described and we have extended its characterization. Two other c3
      type cytochromes, not previously observed, have also been characterized. These
      include an acidic tetraheme cytochrome c3 of molecular mass 15 kDa and an
      octaheme dimeric cytochrome c3 with a native size of 35 kDa. This is the first
      report of the presence of two distinct tetraheme cytochromes c3 in a
      Desulfovibrio species. The physico-chemical properties of the three cytochromes,
      including optical properties, iron content, cysteine and histidine content, N
      terminal amino sequence and redox properties, are characteristic of cytochrome c3
      family. The acidic tetraheme cytochrome c3 exhibited similar midpoint potential
      values for all four hemes (Em1 = -210 mV; Em2 = -240 mV; Em3 = -260 mV; Em4 = 
      270 mV), whereas in the basic tetraheme cytochrome c3 one heme had a much more
      positive potential than the others (Em1 = -90 mV; Em2 = -260 mV; Em3 = -280 mV;
      Em4 = -290 mV). The acidic tetraheme cytochrome c3 exhibited unique properties
      including amino-acid composition and poor reactivity towards hydrogenase.
      However, it is readily reduced by this enzyme in the presence of the basic
      cytochrome c3. The weak reactivity of the acidic tetraheme cytochrome c3 towards
      hydrogenase has been correlated with its low content of basic residues.

PMID- 8573596
TI  - Reconstitution of the F1-ATPase activity from purified alpha, beta, gamma and
      delta or epsilon subunits with glutathione S-transferase fused at their amino
      termini.
AB  - Systems for overexpression and purification of active alpha, beta and gamma
      subunits of Escherichia coli H(+)-ATPase were established. The alpha and beta
      subunits recovered as soluble form were purified by hydroxyapatite column
      chromatography. Since the gamma subunit was overexpressed as the insoluble form,
      this subunit was purified by polyacrylamide gel-electrophoresis containing sodium
      dodecyl sulfate. By subsequent denaturation of this subunit with guanidine
      hydrochloride and renaturation, the active gamma subunit for reconstitution of
      the F1-ATPase activity with the purified alpha and beta subunit was obtained. The
      delta and epsilon subunits which were fused to the carboxy terminus of
      glutathione S-transferase (GST) were overproduced and purified by affinity
      chromatography. These fused proteins (delta-GST and epsilon-GST) were incubated
      with the purified alpha, beta and gamma subunits and applied to affinity
      chromatography. The alpha beta gamma delta-GST and alpha beta gamma epsilon-GST
      complex were eluted specifically by addition of glutathione and exhibited high
      and low ATPase activity, respectively, with a subunit stoichiometry similar to
      that in the native F1-ATPase, indicating that active complexes could be
      reconstituted with the fused proteins. These results suggested that the amino
      terminal ends of the delta and epsilon subunits are not involved in formation of
      the active complex. The fused epsilon-GST bound the gamma subunit strongly, and
      the alpha subunit weakly. The delta-GST bound the gamma subunit significantly,
      and the alpha and beta subunits very weakly.

PMID- 8573597
TI  - Benefits of advanced gel electrophoresis data analysis methods.
AB  - Significantly more information can be obtained if sample mobilities are measured
      at several gel concentrations (%T) and evaluated on the basis of a mathematical
      physical model. This allows one to exploit differences in particle size, charge
      and shape, and results in the following advantages: (i) Charge and size isomers
      of proteins can be detected. It is possible to separate components of similar
      size, but different surface net charge density. (ii) Samples yielding patterns
      with no discernible peaks can be evaluated to produce size and charge
      distribution profiles, as shown for protein-conjugated meningitis vaccines.
      Particle distributions are calculated from 2-D Serwer-type gels. (iii) Different
      DNA conformations are recognized and reasonable size estimates are available for
      anomalously migrating DNA species (e.g., bent kinetoplast DNA) or DNA complexes
      (nucleosome core particles).

PMID- 8573598
TI  - Comparative 2D-electrophoretic mapping of human and rodent hepatic stress
      proteins as potential biomarkers.
AB  - Toxicologic studies in rodents demonstrate that two-dimensional polyacrylamide
      gel electrophoresis of proteins (2DE) is very useful in the detection and
      evaluation of chemical toxicity by providing information regarding cellular
      status at the molecular level. Identification of a set of specific biomarkers of
      exposure or effect, with a proclivity for both a particular rodent and human
      target tissue, is required for development of an electrophoretically based
      testing system. In this regard, stress proteins, such as the heat shock and
      glucose-regulated proteins (Hsp and Grp), are appropriate candidates. The present
      investigation was undertaken to identify these stress proteins on conventional
      two-dimensional electrophoretic gel patterns of human and rat liver homogenates.
      The following stress proteins were identified, their x, y coordinate positions
      mapped, and abundances determined, and these data statistically analyzed and
      compared: Hsp25, Hsp32, Hsp60, Hsc70, Hsp70, Hsp90, Grp75, Grp78, Grp94, protein
      disulfide isomerase (PDI), and ER-60. With the exception of Hsp25 and Hsp32, the
      stress proteins examined were constitutively expressed at detectable levels in
      both unstressed human and rat liver; in virtually identical patterns. Based on
      our results, the human hepatic 2DE stress protein pattern seems well-suited to
      toxicologic screening particularly in in vitro applications and via
      extrapolations from rodent exposures.

PMID- 8573599
TI  - The protein disease database of human body fluids: I. Rationale for the
      development of this database.
AB  - We are developing a relational database to facilitate quantitative and
      qualitative comparisons of proteins in human body fluids in normal and disease
      states. For decades researchers and clinicians have been studying proteins in
      body fluids such as serum, plasma, cerebrospinal fluid and urine. Currently, most
      clinicians evaluate only a few specific proteins in a body fluid such as plasma
      when they suspect that a patient has a disease. Now, however, high resolution two
      dimensional protein electrophoresis allows the simultaneous evaluation of 1,500
      to 3,000 proteins in complex solutions, such as the body fluids. This and other
      high resolution methods have encouraged us to collect the clinical data for the
      body fluid proteins into an easily accessed database. For this reason, it has
      been constructed on the Internet World Wide Web (WWW) under the title Protein
      Disease Database (PDD). In addition, this database will provide a linkage between
      the disease-associated protein alterations and images of the appropriate proteins
      on high-resolution electrophoretic gels of the body fluids. This effort requires
      the normalization of data to account for variations in methods of measurement.
      Initial efforts in the establishment of the PDD have been concentrated on
      alterations in the acute-phase proteins in individuals with acute and chronic
      diseases. Even at this early stage in the development of our database, it has
      proven to be useful as we have found that there appear to be several common acute
      phase protein alterations in the plasma and cerebrospinal fluid from patients
      with Alzheimer's disease, schizophrenia and major depression. Our goal is to
      provide access to the PDD so that systematic correlations and relationships
      between disease states can be examined and extended.

PMID- 8573600
TI  - The Protein Disease Database of human body fluids: II. Computer methods and data
      issues.
AB  - The Protein Disease Database (PDD) is a relational database of proteins and
      diseases. With this database it is possible to screen for quantitative protein
      abnormalities associated with disease states. These quantitative relationships
      use data drawn from the peer-reviewed biomedical literature. Assays may also
      include those observed in high-resolution electrophoretic gels that offer the
      potential to quantitate many proteins in a single test as well as data gathered
      by enzymatic or immunologic assays. We are using the Internet World Wide Web
      (WWW) and the Web browser paradigm as an access method for wide distribution and
      querying of the Protein Disease Database. The WWW hypertext transfer protocol and
      its Common Gateway Interface make it possible to build powerful graphical user
      interfaces that can support easy-to-use data retrieval using query specification
      forms or images. The details of these interactions are totally transparent to the
      users of these forms. Using a client-server SQL relational database, user query
      access, initial data entry and database maintenance are all performed over the
      Internet with a Web browser. We discuss the underlying design issues, mapping
      mechanisms and assumptions that we used in constructing the system, data entry,
      access to the database server, security, and synthesis of derived two-dimensional
      gel image maps and hypertext documents resulting from SQL database searches.

PMID- 8573601
TI  - Feasibility of electrophoresis of a subcellular-sized particle in polymer
      solutions, using automated horizontal gel apparatus.
AB  - Electrophoresis in polymer solutions of a fluorescently labeled polystyrene
      carboxylate particle of 46.5 nm radius was carried out in a horizontal gel
      electrophoresis apparatus with intermittent scanning of the migration path.
      Polymers of the order of 10(6) (dextran, polyvinylpyrrolidone, polyacrylamide and
      polyethyleneglycol) and 10(5) (hydroxyethylcellulose, polyethyleneglycol) M(r)
      were used. In each application, bands formed, became symmetric and narrowed with
      increasing polymer concentration. The decrease in dispersion coefficients, D',
      with polymer concentration was sharpest with the polymers of M(r) 10(6); but
      significant differences in the effectiveness of polymers within that group also
      exist which are not accounted for. Provided that the demonstrated feasibility of
      banding in concentrated polymer solutions will allow for separations similar to
      those achieved at low polymer concentrations in CZE, the method promises to
      overcome the inherent shortcomings of capillary electrophoresis in polymer
      solutions with regard to inaccessibility of bands for immunological and affinity
      detection as well as to preparative scale and preparative instrumental
      complexity.

PMID- 8573602
TI  - Molecular sieving by polymer solutions: dependence on particle and polymer size,
      independence of polymer entanglement.
AB  - The previous postulate of collision and displacement mechanisms of molecular
      sieving based on a biphasic plot of retardation coefficient vs particle radius
      ("R-plot") was extended and modified in four ways: i) A wider size range of
      particles and polymers confirmed the biphasic nature of the R-plot and, in
      addition, revealed a third mechanistic phase in the largest size range of
      particles and polymers which exhibits a positive slope in plots of retardation
      coefficient vs log (particle or polymer size), presumably denoting a collision
      mechanism. ii) Peaks of retardation in polyethyleneglycol (PEG) solutions were
      found with a particle M(r) of 10(7) independently of the M(r) of PEG, and with a
      PEG M(r) of 4 x 10(5) independently of particle M(r), showing that the
      retardation mechanism is not qualitatively a function of the particle/polymer
      size ratio as postulated previously, although quantitatively retardation is
      directly related to the size of particle and polymer. iii) Items i) and ii) were
      confirmed using band width in lieu of mobility measurement. iv) The entanglement
      threshold, c*, was found to decrease monotonically across the entire polymer size
      range in which the triphasic retardation takes place. Thus c* cannot be the sole
      cause for a non-monotonic change of retardation or normalized relative bandwidth
      with polymer size and particle size. Moreover, Ferguson plots across c* do not
      reflect it in any way.

PMID- 8573603
TI  - A chemiluminescence-based detection system for human DNA quantitation and
      restriction fragment length polymorphism (RFLP) analysis.
AB  - A protocol for the chemiluminescent detection of restriction fragment length
      polymorphism (RFLP) profiles with the sensitivity of radioisotope-based detection
      systems is presented. RFLP profiles for the loci D2S44, D17S79, D1S7, D4S139, and
      D5S110 were obtained from ten nanograms of HaeIII-digested K562 DNA and 50
      nanograms of human genomic DNA isolated from bloodstains. DNA is transferred to
      an amphoteric membrane using a neutral, high salt transfer procedure.
      Oligonucleotide probes directly conjugated to alkaline phosphatase are hybridized
      to the membranes, then the membranes are incubated with a substrate that emits
      light upon chemical cleavage by the alkaline phosphatase. Several variables were
      investigated to determine the optimum conditions for RFLP profile generation,
      among them transfer conditions, film selection, and exposure conditions. A
      chemiluminscent human DNA quantitation protocol, consistent with the RFLP
      detection protocol, is also presented.

PMID- 8573604
TI  - Human lymphocyte cDNA ordered library analyzed by 2D gel electrophoresis. 3.
      Analysis of individual clones.
AB  - We pursued the goal of obtaining global information on cDNA libraries from
      lymphocytes by combining data on the genes with data on the expressed proteins.
      Ordered libraries enabled us to establish the properties of the clones by direct
      retrieval of individual clones from the matrix (in our system a 24 x 16 x 12
      array). We have picked-upon inspection of radiofluorographs obtained from the
      pools of the library--39 clones and performed a 2D gel analysis on the cell free
      expressed clonal products and have established also their partial nucleotide
      sequences. Details on two such clones are reported; clone CEM1001 is a new gene,
      while clone CEM1002 is a gene for human elongation factor 1-beta.

PMID- 8573605
TI  - Hydrogen ion-dependent oncogenesis and parallel new avenues to cancer prevention
      and treatment using a H(+)-mediated unifying approach: pH-related and pH
      unrelated mechanisms.
AB  - A comprehensive examination of phenomena related to cancer is presented that is
      based on hydrogen ion dynamics, as viewed from the biological, biochemical, and
      biophysical perspective. A model is described that considers an array of cancer
      associated events from oncogenesis to carcinogenesis from this perspective. The
      basic ideas are viewed from various aspects, ranging from the cellular level to
      the clinical situation. The novel types of therapeutic and prophylactic agents
      that result from applying these concepts are elucidated. Considerable insight
      into this modern approach is seen from some of the mechanisms that characterize
      the phenomenon of spontaneous regression of cancer.

PMID- 8573606
TI  - Oncogenic activation of the ret protooncogene in thyroid cancer.
AB  - Recent studies have established that the ret protooncogene is involved in the
      development of thyroid tumors, including medullary and papillary thyroid
      carcinomas. Germ line mutations of the ret protooncogene were identified in
      multiple endocrine neoplasia (MEN) types 2A and 2B that share the clinical
      feature of medullary thyroid carcinoma and pheochromocytoma. MEN 2A mutations
      involved cysteine residues in the extracellular domain and induced disulfide
      linked homodimerization of the Ret protein on the cell surface, leading to
      activation of its intrinsic tyrosine kinase. On the other hand, a single point
      mutation in the tyrosine kinase domain was found in MEN 2B, as well as in 30 to
      40% of sporadic medullary carcinoma. This mutation also resulted in activation of
      Ret tyrosine kinase without the formation of its covalent homodimerization.
      Differences in the mechanisms of ret activation might account for the different
      phenotypes observed in MEN 2A and MEN 2B. In addition, somatic rearrangement of
      the ret protooncogene was frequently detected in papillary thyroid carcinoma,
      particularly from adult Europeans. A recent report demonstrated that the same
      rearrangement was observed in approximately 60% of papillary carcinomas of
      children from areas contaminated by the Chernobyl accident, suggesting that ret
      rearrangement was induced as a direct consequence of radiation exposure. In this
      review, I focus on the ret mutations detected in thyroid cancer and discuss the
      mechanisms of its oncogenic activation.

PMID- 8573607
TI  - Verruga peruana: an infectious endemic angiomatosis.
AB  - Microbial-related dysplastic and neoplastic angiomatous proliferative processes
      are seen with increased frequency, particularly in the acquired immunodeficiency
      syndrome (AIDS). The microbial-encoded or -induced mediators of angiopathogenesis
      in AIDS-associated Kaposi's sarcoma and bacillary angiomatosis are actively being
      sought. The present review addresses the historical, epidemiologic, clinical,
      etio- and histopathogenic aspects of the verruga peruana (VP). VP is a disease
      thus far endemic to high Andean valleys and characterized by dermal angioblastic
      proliferation in association with reactivation of latent Bartonella bacilliformis
      organisms. VP closely resembles AIDS-associated angiopathogenic manifestations at
      the clinical, histopathologic, and etiologic levels and therefore has been
      proposed as a model for the study of angiogenesis and endothelial cell dysplasia
      and neoplasia. Moreover, the recent epidemic outbreaks in endemic areas, the
      increased frequency of international travel to the region, the variable
      incubation period, and the possibility of not recognizing VP due to its rarity
      further underscore the relevance of studying this rare disorder and of including
      it in the differential diagnosis of angiomatous-proliferative disorders.

PMID- 8573608
TI  - T and Tn pancarcinoma markers: autoantigenic adhesion molecules in pathogenesis,
      prebiopsy carcinoma-detection, and long-term breast carcinoma immunotherapy.
AB  - Physical and chemical nature of the T and Tn pancarcinoma [CA] glycopeptide
      epitopes [EPs], which are immediate precursors of the blood group MN EPs, and
      their role in CA pathogenesis and in clinical disease are discussed. T/Tn are
      immuno-occluded in non-CA diseased and in healthy tissues. Well-differentiated
      CAs usually express a higher proportion of T than Tn EPs, while Tn predominates
      in poorly differentiated primary CAs. Measurement of density of T and Tn EP
      expression on primary breast CA permits disease prognostication. CA-T and -Tn are
      cell adhesion molecules involved not only in invasion but also in metastasis.
      Immunological methods readily detect in vivo autoimmune responses to CA-T and -Tn
      EPs in about 90% of all CA patients from incipience and throughout. Everyone has
      preexisting anti-T and anti-Tn antibodies [Abs] induced by the intestinal flora.
      T/anti-T immunoassays are highly efficient in detection of incipient and
      clinically overt CAs and, importantly, predicted CA in 77% of the patients,
      months to many years before their biopsy/X-ray turned positive; there were no
      false immune predictions of CA. Since 1974, we use human O MN red cell-derived
      T/Tn glycoprotein vaccine plus adjuvants successfully in safe, specific,
      effective, long-term, active immunotherapy against recurrence of advanced breast
      CA pTNM Stages IV, III, and II.

PMID- 8573609
TI  - Overregulation is an unnecessary hindrance to human gene therapy.

PMID- 8573610
TI  - Development and analysis of retroviral vectors expressing human factor VIII as a
      potential gene therapy for hemophilia A.
AB  - To develop a potential gene therapy strategy for the treatment of hemophilia A,
      we constructed several retroviral vectors expressing a B-domain-deleted factor
      VIII (FVIII) cDNA. We confirmed previous reports that when the FVIII cDNA is
      inserted into a retroviral vector, the vector mRNA is decreased resulting in
      significantly (100- to 1,000-fold) lower vector titers. In an attempt to overcome
      this inhibition we pursued two independent strategies. First, site-directed
      mutagenesis was employed to change the structure of a putative 1.2-kb FVIII RNA
      inhibitory sequence (INS). Second, the FVIII gene was transcribed from a
      retroviral vector containing a 5' intron. Results demonstrated that the intron
      increased FVIII expression up to 20-fold and viral titer up to 40-fold but
      conservative mutagenesis of the putative FVIII INS region failed to yield a
      significant increase in FVIII expression or titer. Using the improved FVIII
      splicing vector, we transduced a variety of cell types and were able to
      demonstrate relatively high FVIII expression (10-60 ng of FVIII/10(6) cells/24
      hr). These results underscore the usefulness of these transduced cell types for
      potential in vivo delivery of FVIII.

PMID- 8573611
TI  - Transduction of rIL-2 expanded CD4+ and CD8+ ovarian TIL-derived T cell lines
      with the G1Na (neor) replication-deficient retroviral vector.
AB  - We have expanded ovarian tumor-infiltrating lymphocytes (TIL) in low
      concentrations of recombinant interleukin-2 (rIL-2) to conduct intraperitoneal
      adoptive immunotherapy trials in patients with ovarian cancer. We have previously
      demonstrated that certain T cell lines and clones derived from ovarian TIL
      exhibit in vitro autologous tumor-specific cytotoxicity and/or cytokine
      production (interferon-gamma, tumor necrosis factor-alpha) preferentially in
      response to autologous tumor cells. Studies that utilize a marker gene introduced
      into the DNA of TIL can provide useful information on specific uptake or
      localization of TIL at tumor sites and on the survival of TIL in vivo. We have
      conducted a series of preclinical experiments in which we have successfully
      transfected TIL with G1Na, which encodes the gene for neomycin phosphotransferase
      (neoR). NeoR was detected in at least 10% of CD8+ cells (mean = 10.4%) and
      between 2.5 and 20% of CD4+ TIL (mean = 8.5%). Transduction of ovarian TIL with
      G1Na caused no substantial changes to the T cell phenotypes or in vitro
      cytotoxicities against ovarian and hematogenous tumor cell targets, or on the rIL
      2 requirements of TIL for growth and proliferation. In addition, the intact G1Na
      provirus in transduced TIL cells was rescuable by replication-competent
      retrovirus and was transferred into the genome of NIH-3T3 fibroblasts, which were
      rendered resistant to G418. An enhanced polymerase chain reaction (PCR) procedure
      utilizing detection by ethidium bromide staining was developed. The enhanced PCR
      detected 1 in 100,000 neoR-labeled cells. Furthermore, detection of the G1Na
      genome in transduced TIL by in situ hybridization with an RNA probe provided
      evidence for expression of the neoR gene in transduced TIL. Results obtained from
      these studies suggest that ovarian TIL-derived T cell lines transduced with the
      neoR gene post infection with the G1Na retroviral vector can be utilized to
      examine the in vivo trafficking pattern of ovarian TIL-derived T cell lines
      expanded in low concentrations of rIL-2 and their survival.

PMID- 8573612
TI  - FK506 immunosuppression to control the immune reactions triggered by first
      generation adenovirus-mediated gene transfer.
AB  - Despite good initial success in vivo, gene transfer using first-generation
      replication-defective adenovirus has been reported to lead to transient reporter
      gene expression and to trigger inflammatory reactions in various organs and
      animal models. To gain more knowledge on this phenomenon, immune reactions were
      investigated following in vivo transfection of adult immunocompetent mouse muscle
      using a delta E1/E3a adenoviral vector encoding a beta-galactosidase (beta-Gal)
      expression cassette. Cellular and humoral immune reactions, and rejection of beta
      Gal-positive muscle fibers, occurred within 3 weeks. The muscles showed massive
      infiltration by macrophages, natural killer cells, and CD8+ leukocytes. The mRNA
      levels of granzyme B and interferon-gamma were increased 6 days after vector
      injection, indicating that the infiltrating lymphocytes were activated.
      Antibodies were formed against the adenovirus group antigen and the beta-Gal gene
      product 2 weeks after construct injection. The immunosuppressant FK506, however,
      blocked the cellular infiltration and the humoral response and allowed strong,
      stable transgene expression over 1 month. These data emphasize the immune
      problems related to the use of delta E1/E3a adenoviruses as vectors for gene
      therapy, and they underline the potential of FK506 as an immunosuppressant
      adjunct treatment for adenovirus-mediated gene transfer.

PMID- 8573613
TI  - Purification of a type 5 recombinant adenovirus encoding human p53 by column
      chromatography.
AB  - We have investigated the use of column chromatography for the purification of
      ACN53, a recombinant adenovirus type 5 encoding the human p53 tumor suppressor
      protein. Anion exchange, size exclusion, hydrophobic interaction, and metal
      chelating resins were tested; each was found to have distinct advantages and
      disadvantages. Based on these data, a rapid method was devised for the
      purification of ACN53. The resultant product was characterized and compared to
      cesium chloride density-gradient purified virus by SDS-PAGE, Western blot
      analysis, absorbance spectrum, total particle-to-infectious particle ratio,
      expression of p53 gene product in Saos-2 cells, growth inhibition of Saos-2
      cells, and contamination by ATCC-293 host cell proteins. The results show that
      column chromatography offers an alternative to ultracentrifugation for the
      purification of recombinant adenoviruses for use in human gene therapy trials and
      other research applications.

PMID- 8573614
TI  - Prostate tissue specificity of the prostate-specific antigen promoter isolated
      from a patient with prostate cancer.
AB  - We have cloned and characterized a 620-bp fragment of DNA that flanks 5' of the
      prostate-specific antigen (PSA) gene from a prostate cancer patient. Using DNA
      transfection, the efficacy of this putative promoter in regulating gene
      expression was quantitated in several prostate and nonprostate tissue cell lines.
      Our results demonstrated that the 620-dp DNA fragment actively drives gene
      expression in LNCaP, a PSA-producing prostate tumor cell line. No promoter
      activity was detected in the non-PSA-producing prostate tumor lines, DU145 and PC
      3, nor in a renal (R11) or breast (MCF-7) cancer cell line. Furthermore, the
      promoter activity could be regulated in vitro by androgen stimulation.
      Dihydrotestosterone (DHT) concentrations between 3 and 30 nM induced the highest
      promoter activity in the transfected LNCaP cells, which parallels the expression
      profile of the androgen receptor in LNCaP cells. In addition, our PSA promoter
      exhibited competitive inhibition of the endogenous genomic PSA promoter in
      transfected LNCaP cells, suggesting that prostate cell-specific DNA-binding
      proteins are required to activate the PSA promoter. increased its potency four-
      to five-fold while retaining tissue specificity. Our data suggest that a strong
      tissue-specific negative regulatory element capable of overriding the nonspecific
      CMV promoter is present in the PSA promoter and confers its tissue specificity.
      The use of a highly specific promoter-driven gene vector will allow selective
      expression of therapeutic genes within PSA-producing prostate cancer cells,
      providing a unique strategy for prostate cancer gene therapy.

PMID- 8573615
TI  - A human melanoma cell line transduced with an interleukin-4 gene by a retroviral
      vector releases biologically active IL-4 and maintains the original tumor
      antigenic phenotype.
AB  - Experimental models of vaccination with tumor cells engineered to produce
      interleukin-4 (IL-4) have shown that the local release of this cytokine is
      associated with the development of antitumor immunity that may induce regression
      of established cancer. The aim of this study was to transduce a human melanoma
      cell line with the gene coding for human IL-4, and to analyze cytokine
      production, phenotypic characteristics, and antigen expression after
      transduction. A retroviral vector, constructed by inserting IL-4 cDNA into the
      LXSN vector, was used to infect the human melanoma cell line Me14932, known to
      express the MHC class I HLA-A2 and the melanoma-associated antigen Melan-A/MART
      1, recognized by HLA-A2-restricted T-cells. The confluence of all G418-resistant
      cells (Me14932/IL-4) was then analyzed for proviral integration and IL-4 mRNA
      expression. Substantially stable IL-4 release was detected by ELISA in the
      supernatant of transduced cells, ranging from 1.6 to 4.6 ng/ml per 10(5) cells
      per 24 hr; such a cytokine displayed a specific biologic activity, as revealed by
      the stimulation of blast cell proliferation and the inhibition of lymphokine
      activated killer cell (LAK) induction by IL-2. After 200 Gy irradiation, IL-4
      release remained detectable for 5 weeks, whereas cell proliferation ceased within
      7 days. Morphology and immunophenotypic characteristics of the parental cell line
      (expression of MHC classes I and II, ICAM-1, LFA 3, melanoma-associated antigens,
      etc.) were retained by the IL-4 gene-transduced melanoma as assayed by microscopy
      and immunofluorescence; likewise, susceptibility to lysis by LAK cells as well as
      a T-cell clone recognizing the Melan-A/MART-1 antigen did not change. These
      results, together with the lack of replication-competent retrovirus, suggest that
      the Me14932/IL-4 cell line displays suitable characteristics for its use in the
      treatment of HLA-matched melanoma patients.

PMID- 8573616
TI  - HIV-regulated diphtheria toxin A chain gene confers long-term protection against
      HIV type 1 infection in the human promonocytic cell line U937.
AB  - Gene therapy approaches have recently been investigated for the treatment of
      acquired immunodeficiency syndrome (AIDS), both in preclinical and clinical
      studies, because more traditional antiviral agents have proven to be of limited
      effectiveness. We have previously shown that long-term protection against both
      laboratory and clinical isolates of human immunodeficiency virus type 1 (HIV-1)
      was conferred by HIV-regulated diphtheria toxin A (DT-A) chain in a human T cell
      line. Because the monocyte/macrophage cell is an important reservoir for HIV-1 in
      infected individuals, we sought here to determine whether HIV-regulated DT-A
      would also be effective in the promonocytic cell line U937. We report here that
      long-term protection, conferred by HIV-regulated DT-A, was observed in U937
      cells, but that protection was dependent on the stock of HIV IIIB used for
      challenge. HIV production was measured by p24 assays, polymerase chain reaction
      (PCR) for HIV vif, gag, and reverse transcriptase (RT) sequences, and
      cocultivation with peripheral blood mononuclear cells (PBMCs). Complete
      protection was seen in DT-A-transduced cells with a stock of IIIB propagated on
      H9 cells and titered on peripheral blood mononuclear cells (PBMCs), while
      protection in these same cells with a second stock of IIIB, propagated and
      titered on H9 cells, was only partial and dose dependent.

PMID- 8573617
TI  - DNA-mediated immunization in mice induces a potent MHC class I-restricted
      cytotoxic T lymphocyte response to the hepatitis B envelope protein.
AB  - The particulate form of the major envelope or surface (S) protein of hepatitis B
      virus (HBV) can be taken up by antigen-presenting cells and processed for class I
      presentation as an exogenous protein. We have used several DNA plasmid vectors
      expressing the HBV envelope proteins to determine whether these sequences are
      able to induce cytotoxic T lymphocyte (CTL) responses in BALB/c mice after
      intramuscular DNA injection. A potent and specific induction was obtained, which
      can be detected ex vivo using either specific or nonspecific (interleukin-2)
      stimulation in cell culture, and the DNA-primed CTL responses are stronger than
      those obtained with protein injection with either stimulation protocol. The CTL
      response induced by DNA-based immunization is both canonical and highly specific
      as indicated by the nature of the epitope presented (amino acids 28-39), the
      class I allele used (Ld), and the T lymphocytes involved (CD8+). The CTL response
      is initiated between 3 and 6 days after DNA injection. By 6-12 days after a
      single DNA injection, ex vivo cytolytic activity is nearly maximal, and similar
      high levels of activity can still be detected 4 months after injection. The
      possibility is discussed that the unusual mode of delivery of the antigen to the
      immune system provided by in situ expression might allow HBV envelope antigen to
      be taken up and processed for class I presentation by in situ expression might
      allow HBV envelope antigen to be taken up and processed for class I presentation
      as an exogenous protein in addition to activating potentially the classical
      endogenous pathway.

PMID- 8573618
TI  - In vivo angiogenesis induced by recombinant adenovirus vectors coding either for
      secreted or nonsecreted forms of acidic fibroblast growth factor.
AB  - In vivo gene transfer of angiogenic growth factors represents a potential
      approach to the treatment of ischemic diseases. The present study examined the in
      vitro and in vivo effects of two replication-deficient recombinant adenovirus
      (Ad) vectors coding for human acidic fibroblast growth factor (aFGF1-154). One
      vector codes for the nonsecreted form of the peptide (AdCMV.aFGF1-154), and the
      other vector codes for a recombinant, secreted form (AdCMV.sp+aFGF1-154).
      AdCMV.NLS beta gal, an adenovirus vector coding for beta-galactosidase (beta
      Gal), was used as a control. Assessment of proliferation of starved human
      umbilical vein endothelial cells infected with AdCMV.aFGF1-154 and AdCMV.sp+aFGF1
      154 (20 pfu/cell) showed approximately 6- and 10-fold increase in cell number
      over control, respectively. Infection with AdCMV.sp+aFGF1-154 and with
      AdCMV.aFGF1-154 enhanced endothelial cell differentiation into capillary-like
      structures in vitro. However, this effect was significantly more pronounced with
      AdCMV.sp+aFGF1-154 than with AdCMV.aFGF1-154. Angiogenesis in vivo was assessed
      by injecting subcutaneously into mice 750 microliters of reconstituted basement
      membrane proteins (Matrigel) and the Ad vectors (2 x 10(8) pfu). After 14 days,
      there was histologic evidence of neovascularization in the animal's tissue
      surrounding the Matrigel plugs with AdCMV.aFGF1-154 and AdCMV.sp+aFGF1-154.
      Further, the hemoglobin content of the Matrigel plugs with AdCMV.aFGF1-154 and
      with AdCMV.sp+aFGF1-154 was, respectively, 2.3- and 2.6-fold higher than with
      AdCMV.NLS beta gal. Together, these observations support the concept that
      adenovirus vectors coding for various forms of acidic FGF1-154 may be used to
      induce angiogenesis in vivo and may provide a new therapeutic approach to
      ischemic diseases.

PMID- 8573619
TI  - Effect of herpes simplex virus thymidine kinase expression levels on ganciclovir
      mediated cytotoxicity and the "bystander effect".
AB  - Transfer of the herpes simplex virus type-1 thymidine kinase (HSV-tk) gene into
      tumor cells followed by ganciclovir (GCV) administration, will provide selective
      tumor cell killing. We studied the effect of herpes simplex virus thymidine
      kinase (HSV-tk) expression level on the HSV-tk/GCV-mediated "bystander effect."
      Clones of HSV-tk-transduced rat glioma cells (9L) were isolated that stably
      expressed with different levels of HSV-tk. All clones studied had similar
      sensitivity to ganciclovir with IC50 values ranging from 0.45 to 1.3 microM.
      Within certain enzyme level thresholds, in vitro evaluation of the bystander
      effect has shown that clones with higher level of HSV-tk expression exhibited a
      better bystander effect. Interestingly, the bystander effect was observed between
      different cell types. Both the transduction efficiency and bystander effect are
      essential factors for the success of the antitumor effect by the HSV-tk/prodrug
      GCV suicide gene system.

PMID- 8573620
TI  - Recombinant truncated dystrophin minigenes: construction, expression, and
      adenoviral delivery.
AB  - Duchenne muscular dystrophy (DMD) is a lethal genetic disorder for which there is
      currently no effective treatment. Although clinical application of adenoviral
      vector-mediated gene transfer has not been fully developed, it shows promise for
      the treatment of DMD. One significant problem posed by adenoviral vector-mediated
      gene transfer for DMD is that currently available adenoviral vectors cannot
      accommodate the entire 14-kb dystrophin cDNA. To address this problem, we
      selectively deleted regions of the murine dystrophin cDNA to produce truncated
      constructs. We created three constructs, each with an in-frame deletion of a
      segment (3.0, 4.4, and 5.7 kb) of the spectrin-like repeat region of dystrophin.
      As an additional modification, we removed the majority of the 3' untranslated
      region of the cDNA in expression vectors encoding some of these truncated
      constructs. Comparative quantitative expression studies after transfection into
      COS and C2C12 mouse muscle cells demonstrate variations in the level of
      expression with different deletions in the spectrin-like repeat region.
      Furthermore, deletion of the 3' untranslated region was tested for one
      recombinant construct and resulted in a reduction in the level of expression in
      both cell culture systems. Toward the ultimate goal of gene transfer therapy for
      DMD, we created an adenoviral vector from one of our truncated constructs. Using
      this vector, we demonstrated truncated dystrophin expression in vitro in primary
      mdx (dystrophin-deficient) muscle cells and in vivo in mdx mouse muscle. In vivo,
      recombinant dystrophin was properly localized to the muscle membrane.

PMID- 8573621
TI  - Modification of nasal epithelial potential differences of individuals with cystic
      fibrosis consequent to local administration of a normal CFTR cDNA adenovirus gene
      transfer vector.
AB  - Mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR)
      manifest on the nasal epithelial surface of individuals with cystic fibrosis (CF)
      by Na+ hyperabsorption and diminished beta-agonist-induced Cl- conductance,
      resulting in an abnormal bioelectric phenotype across the nasal epithelium. A
      clinical trial was conducted to determine if a replication-deficient, recombinant
      adenovirus vector containing a normal copy of the CFTR cDNA (AdCFTR) could, when
      administered to the nasal epithelium, correct the abnormal bioelectric phenotype.
      Nine individuals with CF received 2 x 10(5) to 2 x 10(8.5) plaque forming units
      of AdCFTR to the epithelium of one nostril. Measurements made included: baseline
      electrical potential difference (PD) between the surface of the nasal epithelium
      and the interstitial fluid, change in PD in response to amiloride, which inhibits
      apical Na+ channels, and change in PD in response to isoproterenol in a low Cl-
      solution, a measure of cAMP-regulated Cl- conductance. The functional integrity
      of the epithelium was evaluated by the PD response to ATP. Each individual served
      as their own control with measurements made in the nostril to be treated before
      AdCFTR administration, and in the contralateral untreated nostril. On the
      average, in the treated nostril over 2 weeks after the local administration of
      the adenovirus vector compared to measurements made in the same nostril before
      treatment, baseline PD decreased toward normal (-53.3 +/- 4.0 to -34.6 +/- 3.4, p
      = 0.01), response to amiloride decreased toward normal (36.9 +/- 4.7 to 19.7 +/-
      3.0, p = 0.02), and response to low Cl- and isoproterenol increased toward normal
      (-4.5 +/- 1.5 to -9.1 +/- 2.1, p = 0.05). There were no changes in response to
      ATP (-15.3 +/- 2.7 to -15.8 +/- 1.9, p = 0.39), suggesting that the epithelium
      remained functionally intact. Importantly, there were no significant changes in
      measurements made in the untreated nostril. While limited to the nasal
      epithelium, these data suggest an adenovirus vector can safely deliver sufficient
      CFTR cDNA function to improve the abnormal CF bioelectric phenotype.

PMID- 8573622
TI  - Gene therapy of Parkinson disease model rat by direct injection of plasmid DNA
      lipofectin complex.
AB  - Lipofectin-mediated gene transfer was used to introduce plasmid harboring the
      tyrosine hydroxylase (TH) gene into the striatum of rats with lesions of the
      nigrostriatal pathway. The rotational asymmetry of Parkinson disease model rat
      was reduced quickly and significantly, suggesting that plasmid-DNA-transfected
      brain cells can generate L-dopa locally in the striatum in quantities sufficient
      to compensate partially for the loss of intrinsic striatal dopaminergic input.
      Immunohistochemical staining and reverse transcription polymerase chain reaction
      (RT-PCR) also confirm that striatal cells can express exogenous TH gene. Such in
      vivo plasmid DNA transfer strategy may be useful in other neurologic disease
      therapy, especially acute brain insults.

PMID- 8573623
TI  - Making filmless radiology work.

PMID- 8573624
TI  - A semiautomatic three-dimensional segmentation method for disarticulation of bone
      structures on spiral computed tomography images.
AB  - The use of binary thresholding for segmenting bone structures on spiral computed
      tomography images is negatively influenced by partial volume effects (PVEs)
      induced by the image acquisition. PVE leads to mixed voxels, making the binary
      decision "bone" or "nonbone" a difficult one to take. As a result, two distinct
      bone structures that are close to each other will often appear to be connected by
      this method. A typical example consists of "acetabulum/femural head" pairs in the
      pelvic region. To separate them, a clinical user must interactively draw a
      disarticulation line. This procedure is time consuming (often interaction in 50
      slices is needed) and leads to unsmooth visualization of the disarticulated areas
      (by three-dimensional [3D] rendering techniques). We developed a semiautomatic
      cutting algorithm that leads to smooth disarticulated surfaces and considerably
      decreases the amount of user interaction. A sheet detection operator is applied
      to automatically separate bone structures. Detected sheets are used as
      disarticulation lines. Postprocessing ensures that sheets not relevant for the
      application do not influence the resulting image. Our approach is encapsulated in
      an interactive segmentation environment based on thresholding and 3D connected
      component labeling. Results are shown for pelvic region, wrist, and foot bone
      disarticulations.

PMID- 8573625
TI  - Quality assurance and quality control of an intensive care unit picture archiving
      and communication system.
AB  - Most radiology departments have established quality assurance (QA) and quality
      control (QC) programs for conventional film-based image management systems. At
      many institutions, digital image management systems, or picture archiving and
      communication systems (PACS), are replacing part or all of the film management
      system. In these situations, it is important to control the quality of the
      digital images that are produced. The observed frequency of eight types of image
      related errors occurring on an image viewing station located in a medical
      intensive care unit is reported. Images on the viewing station were checked for
      12 consecutive weeks. Film images available in the radiology reading room and
      digital images on the viewing station were compared with a list of completed
      examinations produced by the radiological information system. Overall, 1,082
      patient examinations were encountered. Seventy-six images (7.02% of all images)
      were observed with errors. In addition, four previously unencountered types of
      errors were observed in 11 images (1.01% of all images). The majority of the
      errors are attributed to interfaces either between information systems or between
      the PACS and the user. It is concluded that QA-QC procedures are necessary for
      PACS, and that good interfaces, both between information systems and between
      humans and computer systems, are essential for successful PACS implementations.

PMID- 8573626
TI  - Contrast, noise, and blur affect performance and appreciation of digital
      radiographs.
AB  - We have studied the effect of the simultaneous variation of contrast, noise, and
      blur on the perceived quality of digital radiograph images. Three images were
      processed with different levels of roentgen photon noise, different luminance
      (gray-level) ranges, and different amounts of Gaussian blur. Observers had to
      rate the quality of the images on a numerical scale. To study how the quality
      judgment is related to the visibility of small details (diagnostic quality), an
      artificial detail was added to each image. The detail could be in two possible
      locations. The visibility of this detail was measured in a two-alternative forced
      choice experiment. One of the conclusions is that the quality judgment was based
      mainly on blur, whereas the visibility of details was affected mostly by noise.

PMID- 8573627
TI  - Data clustering and other archive retrieval strategies for teleradiology and
      picture archiving and communication systems.
AB  - A key advantage in the conversion from film-based to digital radiology is the
      possibility of a long-term on line electronic archival of patient studies. The
      popular approach based on optical disk jukeboxes for the long-term archive and
      magnetic disk storage for data caching is not economically attractive because of
      the cost of both the jukebox and the medium. Strategies for extending the
      archival system design with a tape jukebox have been studied. The proposed
      strategy calls for the use of high-ratio lossy compression together with low-cost
      tape storage to make long-term on line archiving more affordable. An intelligent
      prefetching algorithm based on hospital information system and radiologic
      information system triggers, which in turn are augmented by manual case
      preparation, can effectively overcome the longer latency of ad hoc retrievals.
      This longer latency is caused by both system-level bottlenecks and the sequential
      access constraint of the tape drive. Strategies for image clustering and tape
      allocation by patient classification also enhance retrieval efficiency. This
      archival design using image compression, prefetching, and clustering could be
      implemented in many of the existing teleradiology and picture archiving and
      communication systems.

PMID- 8573628
TI  - Quantitative evaluation of low-cost frame-grabber boards for personal computers.
AB  - Nine moderately priced frame-grabber boards for both Macintosh (Apple Computers,
      Cupertino, CA) and IBM-compatible computers were evaluated using a Society of
      Motion Pictures and Television Engineers (SMPTE) pattern and a video signal
      generator for dynamic range, gray-scale reproducibility, and spatial integrity of
      the captured image. The degradation of the video information ranged from minor to
      severe. Some boards are of reasonable quality for applications in diagnostic
      imaging and education. However, price and quality are not necessarily directly
      related.

PMID- 8573629
TI  - Chemiluminescence in drug assay.
AB  - The phenomenon of chemiluminescence allows the development of simple analytical
      procedures using low cost instrumentation which can be easily controlled by
      computers. The sensitivity of the methods is excellent, and selectivity is
      improved by high-performance liquid chromatographic separation. A broad area of
      chemiluminometric applications is drug analysis, which is reviewed in this paper.

PMID- 8573630
TI  - A gas-chromatographic assay method for busulfan with sensitivity for test dose
      therapeutic monitoring.
AB  - A gas-chromatographic assay method was developed and validated for determination
      of busulfan in human plasma for test dose therapeutic drug monitoring. Busulfan
      and the internal standard (1,6-bis-(methanesulfonyloxy)hexane) were extracted
      from plasma samples and derivatized with 2,3,5,6-tetrafluorothiophenol prior to
      gas chromatographic determination. The 63Ni electron-capture detector provided a
      limit of quantitation of 0.0100 micrograms ml-1 busulfan in plasma with a linear
      response over the concentration range 0.0100-0.400 micrograms ml-1. Extraction
      and derivatization yields were 85.3%-91.0% and greater than 95%, respectively.
      Assay specificity for busulfan in the presence of potential metabolites was
      demonstrated. Potentially co-administered drugs gave no response under the sample
      preparation and chromatographic conditions described for quantification of
      busulfan. The applicability of this assay to the individualization of busulfan
      therapy based on a 2 mg test dose is discussed.

PMID- 8573631
TI  - A competitive enzyme linked immunosorbent assay for the determination of N
      acetyltransferase (NAT2) phenotypes.
AB  - The ratio of 5-acetylamino-6-amino-3-methyluracil (AAMU) to 1-methylxanthine (1X)
      in urine samples after caffeine ingestion can be used to indicate human N
      acetyltransferase (NAT2) phenotypes. In previous studies, this ratio has been
      determined by LC or capillary electrophoresis. The possibility that this ratio
      could be determined by competitive antigen enzyme linked immunosorbent assays
      (ELISAs) has been investigated. Polyclonal antibodies were raised in rabbits
      against synthetic derivatives of AAMU and 1X, and competitive antigen ELISAs were
      developed after isolation of the IgGs by ion-exchange chromatography. The
      competitive antigen ELISA correctly identified previously determined NAT2
      phenotypes and gave the expected distribution of slow and fast N-acetylators
      within a group of 48 individuals.

PMID- 8573632
TI  - The binding of 5-fluorouracil to native and modified human serum albumin: UV, CD,
      and 1H and 19F NMR investigation.
AB  - 5-Fluorouracil (FU) is an important and widely used antineoplastic drug that is
      carried in the serum by plasma proteins. Protein binding studies of this drug to
      human serum albumin (HSA) have been carried out by several spectroscopic
      techniques. Difference circular dichroism and UV studies provided information on
      the class of binding sites involved in the interaction. In particular,
      displacement experiments showed that FU has at least one secondary binding site
      in the coumarin binding area, but does not interact with the benzodiazepine
      binding area. Binding was also investigated by difference 1H NMR and by measuring
      the increase in the 19F NMR signal of FU when bound to HSA. Finally, evidence was
      obtained that chemical acetylation of Lys199 results in a decreased apparent
      binding affinity constant (nK) for FU. Such a modification is induced under
      physiological conditions by aspirin.

PMID- 8573633
TI  - Simultaneous determination of cefepime and L-arginine in injections by second
      derivative spectrophotometry.
AB  - A simple spectrophotometric assay for the determination of cefepime and L
      arginine in injections is described. Since zero-order spectra showed considerable
      overlap, second-derivative spectrophotometry was used to enhance the spectral
      details. A linear relationship between second-derivative amplitude and
      concentration of each compound was found. Beer's law was obeyed up to 50 and 22
      micrograms ml-1 of cefepime and arginine, respectively, in the second-derivative
      mode. Detection limits were 0.31 and 0.58 micrograms ml-1 for cefepime and
      arginine, respectively. The method, which is rapid, simple and does not require
      any separation step, has been successfully applied to the assay of commercial
      injections containing cefepime and arginine.

PMID- 8573634
TI  - Flow-injection extraction-spectrophotometric determination of bromhexine with
      orange IV.
AB  - An automatic flow-injection photometric method for the determination of
      bromhexine is proposed. The drug was determined by formation of an ion-pair with
      orange IV, extraction into 1,2-dichloroethane and measurement of the absorbance
      at 412 nm of the organic phase. A linear calibration graph was obtained at
      concentrations of 5 x 10(-6)-1.6 x 10(-4) M of bromhexine. Up to 40 samples h-1
      can be processed with an RSD of 0.32-0.88%. The method was applied to the
      determination of bromhexine in blood serum and a pharmaceutical preparation.

PMID- 8573635
TI  - Analysis of sulfamethazine in the presence of sulfamerazine or sulfadiazine by
      first-derivative photochemically induced fluorescence.
AB  - A first-derivative photochemically-induced fluorescence method is proposed for
      the determination of sulfamethazine (SMTZ) in the presence of sulfamerazine
      (SMRZ) or sulfadiazine (SDZ). Linear calibration plots were obtained for SMTZ in
      SMTZ-SMRZ or SMTZ-SDZ binary mixtures with correlation coefficients larger than
      0.999. For SMTZ the lower limits of detection were 7-13 ppb. Recoveries of 91
      114% were obtained in the analysis of SMTZ in pharmaceutical formulations.

PMID- 8573636
TI  - Flow-injection spectrofluorimetric determination of flufenamic and mefenamic acid
      in pharmaceuticals.
AB  - Two sensitive and rapid flow-injection (FI) spectrofluorimetric methods are
      proposed for the determination of flufenamic acid (FF) and mefenamic acid (MF),
      based on the formation of complexes of these compounds with A1(III) in an
      ethanolic medium. The calibration graphs resulting from the measurements of the
      fluorescence at lambda exc = 351 nm and lambda em = 440 nm, and lambdaexc = 355
      nm and lambda em = 454 nm for the complexes with FF and MF, respectively, are
      linear over the range 0.030-1.20 micrograms ml-1 for FF and 0.30-16.1 micrograms
      ml-1 for MF. The methods have been applied to the determination of these drugs in
      pharmaceutical preparations.

PMID- 8573637
TI  - Spectrofluorimetric determination of paracetamol in pharmaceuticals and
      biological fluids.
AB  - A spectrofluorimetric method for the determination of paracetamol is presented,
      based on the oxidation of the analyte to give the fluorophore 2,2'-dihydroxy-5,5'
      diacetyldiaminebiphenyl. Sodium hypochlorite was used as an oxidizing reagent and
      the optimum pH was found to be 10.0 (sodium carbonate-boric acid buffer
      solution). The linear concentration range of application was 0.1-100.0 micrograms
      ml-1 of paracetamol, the detection limit 0.01 micrograms ml-1 and the relative
      standard deviation 1.2%. The method has been satisfactorily applied to the
      determination of paracetamol in pharmaceutical formulations and biological
      fluids.

PMID- 8573638
TI  - Polarographic determination of prenalterol hydrochloride through treatment with
      nitrous acid.
AB  - A simple and sensitive polarographic method is described for the determination of
      prenalterol hydrochloride through treatment with nitrous acid. The different
      experimental parameters affecting the derivatization process, as well as the
      polarographic analysis were studied. The derivatization product was found to be
      reducible at the dropping mercury electrode over the whole pH range in Britton
      Robinson buffers. At pH 5, a well defined diffusion-controlled cathodic wave was
      produced. The limiting current vs. the concentration plot was linear over the
      range 0.015-0.15 mM in the direct current mode, with a minimum detectability of
      0.8 microM. The proposed method was applied successfully to the determination of
      prenalterol hydrochloride either in the pure form or in its dosage forms.

PMID- 8573639
TI  - Electrochemical oxidation of CBS-113 A, a new anti-inflammatory drug:
      applicability to liquid chromatography-electrochemical detection.
AB  - The electrochemical properties of a new non-steroidal anti-inflammatory drug (2
      hydroxy-4-methylphenyl-2-aminothiazole hydrochloride; CBS-113 A) have been
      studied using voltammetry in direct current and cyclic modes at glassy carbon
      disk electrodes. The results show an oxidative process with a diffusion
      controlled and a reversible mechanism; these data agree with those obtained in a
      reversed-phase high-performance liquid chromatography (HPLC) system coupled
      either with amperometric (single glassy carbon electrode) or coulometric
      detection (two porous graphite electrodes in series) set at potentials of +0.65 V
      (vs. Ag/AgCl) and +0.4 V (vs. Pd/H2), respectively. Similar electrochemical
      properties were found for 2-hydroxyphenyl-2-amino-5'-methylthiazole hydrochloride
      (RD-1546) which is a potential internal standard. An HPLC system coupled with a
      UV detector (lambda = 272 nm) and an amperometric detector (+0.65 V) showed a
      gain in sensitivity of about 10 using electrochemical detection (ED) for the
      determination of CBS-113 A in human plasma. Linearity range, precision and
      accuracy were calculated and showed the potential application of HPLC-ED to
      pharmacokinetic studies of CBS-113 A in plasma.

PMID- 8573640
TI  - Assessment of antipyrine kinetics from saliva or plasma: influence of age.
AB  - The purpose of this study was to investigate whether antipyrine estimation in
      saliva provides valid information on plasma antipyrine clearance (APCl) and can
      be useful as an index of changes in drug metabolism with age. Antipyrine kinetics
      was studied in 93 elderly (mean age 82 years) and 23 young (mean age 29 years)
      volunteers. Plasma antipyrine half-life (APt1/2) increased and plasma APCl
      declined with age. No significant difference between plasma- and saliva-derived
      parameters was found in either young or old subjects. However, the saliva/plasma
      ACCl ratio tended to increase with age. A highly significant correlation between
      saliva and plasma APCl or APt1/2 was found in young subjects. Values were less
      closely related in the elderly and the slope of the saliva/plasma APCl
      relationship was significantly different in both groups of subjects. Residual
      variance was higher in the regressions corresponding to the elderly. The findings
      in the study indicate that the relationship between saliva and plasma kinetics in
      young subjects becomes less reproducible with age.

PMID- 8573641
TI  - Determination of some non-steroid anti-inflammatory drugs by capillary
      isotachophoresis.
AB  - The isotachophoretic (ITP) behaviour and separation of the anti-inflammatory
      drugs kebuzone (KB), tribuzone (TB) and phenylbutazone (PB) was studied in the
      operational system of HCl/His (leading electrolyte, LE) and 4-nitrophenol
      (terminating electrolyte, TE). The effective mobilities were 19.4 x 10(-9) m2 V-1
      s-1 for KB, 18.1 x 10(-9) m2 V-1 s-1 for TB and 18.9 x 10(-9) m2 V-1 s-1 for PB
      when using an optimised system with 10 mM HCl + 40 mM His (pH 6.63) as LE and 10
      mM 4-nitrophenol as TE. The calibration graphs were rectilinear (r = 0.9982
      0.9996) in the range 20 to 600 mumol 1-1 of KB, TB or PB. The ITP method was used
      for determining the content of KB, TB or PB in mass-produced pharmaceuticals as
      tablets, coated tablets, injections, and ointments. The results of the ITP
      determination were in good agreement with those of standard pharmacopoeial
      methods.

PMID- 8573642
TI  - Study of the stability of tylosin A in aqueous solutions.
AB  - The decomposition of the 16-membered ring macrolide antibiotic tylosin A in
      aqueous buffers has been investigated in the pH range 2-13, by means of a liquid
      chromatographic assay with ultraviolet detection at 280 nm. In acidic medium,
      tylosin A is converted into tylosin B, while in neutral and alkaline medium,
      tylosin A aldol is formed together with a number of polar decomposition products
      of unknown identity. The decomposition kinetics have been studied as a function
      of the type and concentration of the buffer, ionic strength, pH and temperature.

PMID- 8573643
TI  - A liquid chromatographic method for the determination of promethazine enantiomers
      in human urine and serum using solid-phase extraction and fluorescence detection.
AB  - A LC method was developed for the concurrent assay of R(+) and S(-) promethazine
      from human urine and serum. The method involves the use of solid-phase extraction
      for sample clean-up. Chromatographic resolution of the enantiomers was performed
      under isocratic conditions using a mobile phase of hexane-1,2-dichlorethane
      absolute ethanol-trifluoroacetic acid (400:150:100:1, v/v/v/v) at a flow rate of
      1 ml min-1 on a brush-type column KK-CARNU. The enantiomers were detected by
      fluorescence using an excitation wavelength of 250 nm and a 280 nm emission
      cutoff filter. Chlorpromazine was used as the internal standard for urine
      analysis. Standard addition was used for promethazine analysis from serum. Drug
      to internal standard ratios were linear from 0.25 to 10 micrograms ml-1 in urine.
      Serum levels were linear from 2 to 10 ng ml-1.

PMID- 8573644
TI  - Comparison of reversed-phase liquid chromatography with colorimetry for analysis
      of phenolphthalein preparations.
AB  - The high-performance liquid chromatography (HPLC) method of the United States
      Pharmacopeia has been compared with the colorimetric method of the British
      Pharmacopoeia for the assay of phenolphthalein in various preparations. Results
      are presented for the linearity, sensitivity and reproducibility of the two
      methods. The HPLC method was considered to be more convenient for routine
      analysis of the preparations of phenolphthalein.

PMID- 8573645
TI  - High-performance liquid chromatographic determination of cis
      dichlorodiammineplatinum(II) in plasma ultrafiltrate.
AB  - A reproducible, simple and sensitive high-performance liquid chromatographic
      method was described for the quantitative analysis of cis
      diamminedichloroplatinum(II) (CDDP) in ultrafiltrate plasma in the presence of
      nickel chloride as internal standard. CDDP and the internal standard were
      chelated by exchange with diethyldithiocarbamate. After derivatization, the
      mixture was directly injected into the column. Chromatography was performed on an
      Ultrasphere column and the eluent measured spectrophotometrically at 260 nm for
      CDDP and at 250 nm for the internal standard. The peak area ratio of CDDP to the
      internal standard varied linearly with concentration over the range 0.05-10
      micrograms ml-1. Precision and reproducibility were both excellent and the limit
      of quantification was 0.03 micrograms ml-1 using only 0.5 ml of ultrafiltrate.
      The present method, without extraction, should be entirely automated. This assay
      may be suitable for therapeutic drug monitoring in patients receiving CDDP.

PMID- 8573646
TI  - Determination of pirenzepine in human plasma using liquid chromatography with
      tandem mass spectrometric detection.
AB  - A sensitive (LOQ = 1 ng ml-1) and specific method based on liquid chromatography
      with tandem mass spectrometric (MS/MS) detection has been developed and validated
      for the analysis of pirenzepine (I) in plasma. Sample preparation involved liquid
      liquid extraction of drug and internal standard (IS) from basified plasma. The
      organic extract was evaporated to dryness, and the residue was reconstituted in
      the mobile phase and then injected into the liquid chromatography/MS/MS system.
      Drug, IS, and endogenous impurities were separated using reverse-phase
      chromatography. A Sciex API III tandem mass spectrometer equipped with a heated
      nebulizer was operated in the positive ion mode. Multiple reaction monitoring
      using the parent-->daughter ion combinations of m/z 352-->113 and 629-->422 was
      used to quantify I and IS, respectively. The method was validated in the
      concentration range of 1-100 ng ml-1 plasma with adequate assay precision and
      accuracy, and was utilized to support human safety and tolerability study with I.

PMID- 8573647
TI  - A comparison of disc and cartridge solid-phase extraction for the LC
      determination of rifampin and 25-desacetylrifampin in human serum.

PMID- 8573648
TI  - Microscopic determination of drug solubility in plasma and calculation of
      injection rates with a plasma circulatory model to prevent precipitation on
      intravenous injection.

PMID- 8573649
TI  - Controlling the dynamical behavior of a circle map model of the human heart.
AB  - One-dimensional circle maps are good models for describing the nonlinear
      dynamical behavior of two interacting oscillators. They have been employed to
      characterize the interaction between a periodic external forcing stimulus and an
      in vitro preparation of chick embryonic cardiac cells. They have also been used
      to model some human cardiac arrythmias such as modulated ventricular parasystole.
      In this paper, we describe several techniques involving engineering feedback
      control theory applied to a circle map model of human heart parasystole. Through
      simulations of the mathematical model, we demonstrate that a desired target phase
      relationship between the normal sinus rhythm and an abnormal ectopic pacemaker
      can be achieved rapidly with low-level external stimulation applied to the
      system. Specifically, we elucidate the linear, self-tuning, and nonlinear
      feedback approaches to control. The nonlinear methods are the fastest and most
      accurate, yet the most complex and computationally expensive to implement of the
      three types. The linear approach is the easiest to implement but may not be
      accurate enough in real applications, and the self-tuning methods are a
      compromise between the other two. The latter was successful in tracking a variety
      of period-1, period-2, and period-3 target phase trajectories of the heart model.

PMID- 8573650
TI  - Extending the HKB model of coordinated movement to oscillators with different
      eigenfrequencies.
AB  - We study the dynamics of a system of coupled nonlinear oscillators that has been
      used to model coordinated human movement behavior. In contrast to earlier work we
      examine the case where the two component oscillators have different
      eigenfrequencies. Problems related to the decomposition of a time series (from an
      experiment) into amplitude and phase are discussed. We show that oscillations at
      multiples of the main frequency of the oscillator system may occur in the phase
      and amplitude due to the choice of a coordinate system and how these oscillations
      can be eliminated. We derive an explicit equation for the dynamics of the
      relative phase of the oscillator system in phase space that enables a direct
      comparison between theory and experiment.

PMID- 8573651
TI  - Synchronized oscillations in the visual cortex--a synergetic model.
AB  - We present an oscillator network model for the synchronization of oscillatory
      neuronal activity underlying visual processing. The single neuron is modeled by
      means of a limit cycle oscillator with an eigenfrequency corresponding to visual
      stimulation. The eigenfrequency may be time dependent. The mutual coupling
      strengths are unsymmetrical and activity dependent, and they scatter within the
      network. Synchronized clusters (groups) of neurons emerge in the network due to
      the visual stimulation. The different clusters correspond to different visual
      stimuli. There is no limitation of the number of stimuli. Distinct clusters do
      not perturb each other, although the coupling strength between all model neurons
      is of the same order of magnitude. Our analysis is not restricted to weak
      coupling strength. The scatter of the couplings causes shifts of the cluster
      frequencies. The model's behavior is compared with the experimental findings. The
      coupling mechanism is extended in order to model the influence of bicucullin upon
      the neural network. We additionally investigate repulsive couplings, which lead
      to constant phase differences between clusters of the same frequency. Finally, we
      consider the problem of selective attention from the viewpoint of our model.

PMID- 8573653
TI  - Determination of the precision of spike timing in the visual cortex of
      anaesthetised cats.
AB  - Neuronal cortical spike trains contain precisely replicating patterns whose
      presence cannot be accounted for by change production. A comparison of the number
      of triplets of spikes present two times with the number of doublets replicated
      three times in the same window duration gives a frequency-insensitive measure of
      this type of fine temporal organisation. By varying the tolerance with which such
      precisely replicating patterns are detected, one can evaluate the accuracy of
      spike timing in spike trains. In the sample of data here analysed, it was found
      that replicating patterns were best seen in the precision range 0.4-1.4 ms (a
      result evidently at variance with a simple 'integrate and fire' model of
      neurons). Surprisingly, the fine temporal structure of spike trains thus
      evidenced was stronger at relatively low firing rate discharges and was present
      in both the 'spontaneous' and 'evoked' responses.

PMID- 8573652
TI  - Coordination dynamics of trajectory formation.
AB  - The present study aims to understand the neurally based coordination dynamics
      (multistability, loss of stability, transitions, etc.) of trajectory formation in
      a simple task. Six subjects produced two spatial patterns of coordination in the
      xy plane by alternating the abduction-adduction and flexion-extension motions of
      their right index finger. Each pattern was characterized by a unique temporal
      ratio between the x and y directions of motion: (1) a figure zero, a 1:1 temporal
      pattern; and (2) a figure eight, a 2:1 temporal pattern. The patterns were
      produced rhythmically and movement frequency was scaled across ten frequency
      plateaus, with ten cycles of motion per step. As movement frequency increased,
      switching from a figure eight to a figure zero was observed at critical cycling
      frequencies. The switch from pattern (2) to pattern (1) was identified in the
      spatial trajectory and power spectra of x(t) and y(t). En route to the
      transition, enhancement of fluctuations was observed in the Fourier amplitudes of
      x(t) and y(t), specifically at f0 (the metronome frequency) and 2f0 (the first
      harmonic of f0). Interestingly, there was no difference in the spatial
      variability of the two patterns. Overall, the data demonstrate that spatial
      patterns of coordination can be characterized in terms of the temporal
      relationship between the spatial components of the trajectory itself. We discuss
      the experimental findings in relation to other end-point planning and multijoint
      control strategies, as well as the much more general problem of temporal
      synchronization in many interlimb and intralimb coordination tasks.

PMID- 8573654
TI  - Dynamics control of semantic processes in a hierarchical associative memory.
AB  - A neural mechanism for control of dynamics and function of associative processes
      in a hierarchical memory system is demonstrated. For the representation and
      processing of abstract knowledge, the semantic declarative memory system of the
      human brain is considered. The dynamics control mechanism is based on the
      influence of neuronal adaptation on the complexity of neural network dynamics.
      Different dynamical modes correspond to different levels of the ultrametric
      structure of the hierarchical memory being invoked during an associative process.
      The mechanism is deterministic but may also underlie free associative thought
      processes. The formulation of an abstract neural network model of hierarchical
      associative memory utilizes a recent approach to incorporate neuronal adaptation.
      It includes a generalized neuronal activation function recently derived by a
      Hodgkin-Huxley-type model. It is shown that the extent to which a hierarchically
      organized memory structure is searched is controlled by the neuronal
      adaptability, i.e. the strength of coupling between neuronal activity and
      excitability. In the brain, the concentration of various neuromodulators in turn
      can regulate the adaptability. An autonomously controlled sequence of
      bifurcations, from an initial exploratory to a final retrieval phase, of an
      associative process is shown to result from an activity-dependent release of
      neuromodulators. The dynamics control mechanism may be important in the context
      of various disorders of the brain and may also extend the range of applications
      of artificial neural networks.

PMID- 8573655
TI  - High-order behaviour in learning gate networks with lateral inhibition.
AB  - In this work we present a neural network model incorporating activity-dependent
      presynaptic facilitation with multidimensional inputs. The processing unit used
      is based on a slightly simplified version of the Learning Gate Model proposed by
      Ciaccia et al. (1992). The network topology integrates a well-known biological
      neural circuit with a lateral inhibition connection subnet. By means of
      simulation experiments, we show that the proposed networks exhibit basic and high
      order features of associative learning. In particular, overshadowing and blocking
      are reproduced in the presence of both noise-free and noisy inputs. The role of
      noise in the development of high-order learning capabilities is also discussed.

PMID- 8573656
TI  - Electro-geometrical coupling in non-uniform branching dendrites. Consequences for
      relative synaptic reflectiveness.
AB  - The relationships between somatofugal electronic voltage spread, somatopetal
      charge transfer and non-uniform geometry of the neuronal dendrites were studied
      on the basis of the linear cable theory. It is demonstrated that for the
      dendritic arborization of arbitrary geometry, the path distribution of the
      relative effectiveness of somatopetal synaptic charge transfer defined as in
      Barrett and Crill (1974) is identical to that of the somatofugal steady
      electronic voltage normalized to the voltage at the soma. The features of both
      distributions are determined by breaks in the voltage gradient (the slope of
      monotonic voltage decay) at the sites of local non-uniformity of the dendritic
      geometry, such as abrupt change in diameter and asymmetric branching. If the
      membrane- and cytoplasm-specific electrical parameters are assumed as uniform and
      the branch diameter as piece-wise uniform, then at any site of step change the
      square reciprocal ratio of the pre- and poststep diameters determines the ratio
      of the pre- and poststep electronic gradients. At branching points this ratio is
      modulated by partition of the core current between the daughter branches in
      proportion to their input conductances depending on global geometries of the
      daughter subtrees originating there. Thus, simply computed steady somatofugal
      voltages provide a physiologically meaningful estimation of the relative
      influence of synaptic inputs in different parts of the dendritic arborization on
      the output of the neuron.

PMID- 8573657
TI  - Third-order reverse correlation analysis of muscle spindle primary afferent fiber
      responses to random muscle stretch.
AB  - The response of primary muscle spindle afferent fibers to muscle stretch is
      nonlinear. Now spindle responses (trains of action potentials) to band-limited
      Gaussian white noise length perturbations of the gastrocnemius muscles (input
      signal) are described in cats. The input noise upper cutoff frequency was clearly
      above the frequency range of physiological length changes in cat hindleg muscles.
      The input-output relation was analyzed by means of peri-spike averages (PSAs),
      which could be shown to correspond to the kernels of Wiener's white noise
      approach to systems identification. The present approach (the reverse correlation
      analysis) was applied up to the third order. An experiment consisted of two
      recordings: one (the source recording) to determine PSAs and the other (the test
      recording) to provide an input signal for predicting responses. The predictions
      of different orders were compared with the actual neuronal response (the
      observation) of the test recording. Four different approximation procedures were
      developed to adapt prediction and observation and to determine weighting factors
      for the predictions of different orders. The approximations also yielded the
      value of the power density P of the input noise signal: at a variety of stimulus
      parameters, P from approximations had the same magnitude as P determined directly
      from the input signal amplitude spectrum. The prediction of a sequence of action
      potentials improved the higher the order of components. 37 of 42 action
      potentials of a test recording (the observation) could be confidently predicted
      from PSAs or kernels. Compared with the size of the linear first-order prediction
      curve, the relative sizes of the second and third-order prediction curves were:
      1.0:0.47:0.26.

PMID- 8573658
TI  - Lateralization in the frontal lobes: searching the right (and left) way.

PMID- 8573659
TI  - Evidence for heritability of biogenic amine levels in the cerebrospinal fluid of
      rhesus monkeys.
AB  - Susceptibility to several human psychopathological disorders is under partial
      genetic influence, and many of these disorders have biological correlates that
      may form part of the basis of this vulnerability. In humans, alterations in
      cerebrospinal fluid (CSF) metabolite levels of the amine transmitters
      norepinephrine, dopamine, and serotonin have been associated with several forms
      of psychopathology, and altered levels of these metabolites have been found in
      healthy probands with a familial history of such illnesses. We report evidence
      for heritability of CSF levels of biogenic amine measures in rhesus monkeys,
      Macaca mulatta. In a pilot study of 54 monkeys with known pedigrees, significant
      differences among sire families were found for CSF levels of norepinephrine (p =
      0.04), homovanillic acid (p = 0.02), and 5-hydroxyindoleacetic acid (p = 0.04).
      These data indicate that variation in bioaminergic measures is associated with
      pedigree, and that model systems incorporating both genetic and environmental
      factors can contribute to the understanding of the function of aminergic systems
      implicated in vulnerability to psychopathology.

PMID- 8573660
TI  - Benzodiazepines as antidepressants: does GABA play a role in depression?
AB  - Benzodiazepines, the most widely prescribed psychotropic drugs, are often used in
      patients with depressive disorders, either alone or in combination with standard
      antidepressants. This review evaluates the efficacy of benzodiazepines
      (alprazolam, diazepam, chlordiazepoxide) as established in acute-phase,
      randomized controlled trials (RCTs) in major depressive disorder. Metaanalyses
      using intent-to-treat, as well as adequate treatment exposure samples, revealed
      an overall efficacy of 47-63% and a drug-placebo difference of 0-27% for all
      benzodiazepines. Alprazolam, the best studied of the benzodiazepines, had a 27.1%
      (sd = 6.1%) greater response than placebo, which is comparable to standard
      antidepressants. Alprazolam, in particular, may be a useful treatment option for
      patients in whom standard antidepressant medications are contraindicated, poorly
      tolerated, or possibly ineffective. Alprazolam may have a more rapid onset of
      action for some patients. Benzodiazepines do not primarily affect biogenic amine
      uptake or metabolism, although they do augment gamma-amino butyric acid (GABA)
      activity. The antidepressant efficacy of benzodiazepines, which are GABAA
      receptor agonists, is consistent with the GABA theory of depression.

PMID- 8573661
TI  - Sertraline safety and efficacy in major depression: a double-blind fixed-dose
      comparison with placebo.
AB  - In a 6-week, randomized, double-blind, multicenter trial, sertraline 50 mg, 100
      mg, or 200 mg, or placebo, was administered once daily to 369 patients with DSM
      III-defined major depression. Efficacy variables included changes from baseline
      scores for total Hamilton Rating Scale for Depression (HAMD), HAMD Bech
      Depression Cluster, Clinical Global Impressions (CGI) Severity, CGI Improvement,
      and Profile of Mood States Depression/Dejection Factor. For the evaluable
      patients analysis, all sertraline groups showed significantly (p < 0.05 or
      better) greater improvements in all efficacy variables except one when compared
      with the placebo group. For the all-patients analysis, all efficacy variables in
      the 50 mg group were statistically significantly (p < 0.05) better than placebo.
      Side effects increased with increasing dosage but were usually mild and well
      tolerated. The results of this study show that sertraline 50 mg once daily is as
      effective as higher dosages for the treatment of major depression with fewer side
      effects and therapy discontinuations.

PMID- 8573662
TI  - Combination monoamine oxidase inhibitor and beta-blocker treatment of migraine,
      with anxiety and depression.
AB  - This paper presents the results of a study comparing the effectiveness of a beta
      adrenergic blocking agent, atenolol, a monoamine oxidase inhibitor (MAO-I),
      phenelzine, and the combination in treatment of 61 adults with migraine headache.
      The goals of the study are (1) to investigate the safety of concomitant treatment
      of migraine with beta-blockers and phenelzine, (2) to assess whether orthostatic
      hypertension and other side effects would be relieved, and (3) to compare the
      results of this open trial of phenelzine to those of a previous study using
      similar methods. Phenelzine was associated with a large decrease in the frequency
      and severity of migraine attacks. Anxiety and depression were also reduced by
      phenelzine both alone, and in combination with a beta-blocker. The results show
      that the combination of MAO-I's and beta-blockers can be administered safely, and
      can lead to the reduction in the side effects with either drug alone.

PMID- 8573663
TI  - Induction of cytokine synthesis and fever suppresses REM sleep and improves mood
      in patients with major depression.
AB  - Beneficial effects of inflammatory events on certain psychiatric disorders,
      including depression, were reported sporadically by ancient Greek physicians, but
      have been described also in our times by a few psychiatrists during the past
      decades. During febrile inflammatory events, mediators of the immune system such
      as interleukin-1 can be detected in the brain and may act on their respective
      receptors which have also been demonstrated in the brain. Since cytokines such as
      interleukin-1 have been shown in animal studies to exert sedative behavioral
      effects, to be somnogenic, and to induce slow-wave sleep (SWS), we performed a
      pilot study to evaluate scientifically the anecdotically reported beneficial
      effects of inflammatory states on depressive disorders. Mood and sleep parameters
      were monitored in seven drug-free, severely depressed patients before, during,
      and after the administration of a single dose of endotoxin. All patients
      responded with a short pulse of increased synthesis of the cytokines tumor
      necrosis factor, interleukin-1, and interleukin-6 and elevated body temperature
      for several hours. During the night following endotoxin administration, rapid eye
      movement (REM) sleep was significantly suppressed, while changes in slow wave
      sleep were not significant. During the next day, all patients were in a
      significantly improved mood; however a rebound of REM sleep was observed in the
      second night after endotoxin administration and mood worsened again during the
      next days, indicating an only transient beneficial effect of the treatment.

PMID- 8573664
TI  - P300 amplitude decrements in children from families of alcoholic female probands.
AB  - A total of 70 age- and gender-matched children and their relatives who were from
      families that were either at high or low risk for developing alcoholism were
      studied and the children evaluated using event-related potential paradigms from
      both the auditory and visual modalities. The high-risk children were ascertained
      through families at exceptionally high risk for female alcoholism (half of all
      female first- and second-degree relatives were alcoholic), while low-risk control
      families had been selected for absence of alcoholism in first- and second-degree
      relatives. Results indicate that reduced amplitude of P300 and greater negativity
      of N250 characterize children from high-risk families when evaluated with an
      auditory task. The visual task discriminated high- and low-risk groups for male
      children only, consistent with earlier findings for high-risk families
      ascertained through a male alcoholic. Further, daughters of alcoholic mothers
      (biological father nonalcoholic) display significantly lower P300 than matched
      controls, indicating that transmission of alcoholism risk may be possible from
      mother to daughter without the necessity of paternal alcoholism.

PMID- 8573665
TI  - Quantitative analysis of the inflammatory reaction surrounding sutures commonly
      used in operative procedures and the relation to postsurgical adhesion formation.
AB  - Inflammatory reaction as well as the extent of postsurgical adhesion formation
      are described as varying according to suture material or diameter used. Whether
      the inflammatory reaction influences the formation of adhesions or is a mere
      consequence of surgical trauma itself or of type and amount of foreign body
      material used has never been elucidated entirely. In this study a quantitative
      analysis of both variables was therefore performed, according to previously
      described techniques, and correlated within 120 peritoneal defects of a standard
      side wall-uterine horn adhesion model in the rat. Three different suture
      characteristics, material (Prolene, Vicryl, Catgut), diameter (USP gauges 3/0,
      5/0, 6/0) and knot configuration (2 = 2, S x S x S x S x S) were analysed for
      this purpose. Both the inflammatory reaction and the adhesion percentage showed
      significant differences within and in between suture characteristics, but no
      significant correlation between the two variables was found after statistical
      analysis. The conclusion is made that, when evaluated after 14 d, the extent of
      postsurgical adhesion formation is not related to the inflammatory reaction.

PMID- 8573666
TI  - Porosity in composite resins.
AB  - Porosity in the pastes of composite resins before and after polymerization has
      been measured. The influence of the diameter of the extrusion orifices and the
      spatulation of the chemically-activated pastes has been evaluated. Considering
      that thin layers of these materials are transparent, the investigation has been
      carried out mainly by analysis of approximately 300 microns or lower thickness
      layers, that are still transparent under the microscope. Generally, there was a
      significant dependence of the porosity on the orifice diameter. However, this
      rule showed some exceptions. As far as the chemically-activated pastes were
      concerned, in all examined cases the number of small size (10-40 microns)
      porosities increased after spatulation.

PMID- 8573667
TI  - Preparation and characterization of poly(epsilon-caprolactone) polymer blends for
      the delivery of proteins.
AB  - A series of ternary blend matrices, based on high- and low-molecular-weight
      poly(epsilon-caprolactone) (PCL) and a poly(ethylene oxide)-poly(propylene oxide)
      poly(ethylene oxide) block copolymer (Synperonic L61), has been developed for the
      delivery of proteins. The inclusion of Synperonic L61 served to enhance the water
      content of the matrix available for protein diffusion. Blends comprising high
      molecular-weight PCL (PCLH) and Synperonic L61 alone were found by scanning
      electron microscopy to be incompatible over a wide composition range. The
      addition of a low-molecular-weight PCL (PCLL) enhanced compatibility of the
      polymeric components. Analysis of the dynamic mechanical and thermal properties
      of these blends showed a significant shift in the glass transition temperature of
      the material (-38 to -55 degrees C), as the weight fraction of Synperonic L61
      increased to 30 wt%, indicative of limited miscibility of the components in the
      non-crystalline phase. All ternary blended matrices showed a higher degree of
      hydration relative to homogeneous PCLH. The maximum water content could be
      modified by adjusting the weight fraction of Synperonic L61 in the blend. The
      rate of release of a model protein, bovine serum albumin (BSA), from matrices
      containing Synperonic L61 was considerably higher than that from PCLH and
      PCLH/PCLL alone. Analysis of the release mechanisms of BSA from these matrices
      suggested that, whilst diffusion was the predominant mode of protein transport,
      the elution of Synperonic L61 from blended matrices during the dissolution caused
      a notable deviation from Fickian control.

PMID- 8573669
TI  - Azo polymeric hydrogels for colon targeted drug delivery.
AB  - Azo polymeric hydrogels were developed for colon specific targeting.
      Methacryloyloxy azobenzene was synthesized and hydrogels were prepared by
      copolymerizing with hydroxyethyl methacrylate. These hydrogels were characterized
      by various spectral techniques such as Fourier transform infrared spectroscopy,
      thermogravimetric analysis and scanning electron microscopy. Equilibrium swelling
      measurements of the hydrogels were carried out in distilled water and also in
      simulated gastric and intestinal fluids. The in vitro release studies of the
      incorporated 5-flurouracil were carried out in simulated gastric and intestinal
      fluids. The in vitro release profiles of the drug were also obtained in the
      presence of azoreductase in the culture of intestinal flora. The release was
      faster and almost followed a zero order pattern. This can be attributed to the
      cleavage of the azo crosslinks in the hydrogel by the azoreductase and the
      release of the entrapped drug at the site of targeting i.e., colon.

PMID- 8573668
TI  - In vitro contact phase activation with haemodialysis membranes: role of
      pharmaceutical agents.
AB  - Contact phase activation was investigated in vitro using flat sheet type of
      haemodialysis membranes, Cuprophan (Akzo, Faser, Germany) and AN69S (Hospal,
      France), and a negatively charged polyamide Ultipor NR 14225 membrane as a
      control. The investigation focussed on the determination of factor XII-like
      activity (FXIIA) as an indicator of contact phase activation in the supernatant
      phase and at the membrane surface after plasma-membrane contact using an
      incubation test cell. The findings were compared with the observations from a
      plasma-free system utilizing purified unactivated factor XII. The plasma FXIIA
      bound to the membrane surface was significantly different between the membranes,
      while the supernatant phase FXIIA exhibited no significant differences. In
      contrast, the plasma-free system exhibited significant differences in the
      supernatant FXIIA and membrane-bound FXIIA for all the materials used and the
      magnitude of the activity was significantly greater for negatively charged
      materials. This finding demonstrated the strong influence of the interaction of
      other plasma constituents on the membrane surface and as such the binding and
      subsequent activation of factor XII may be altered possibly due to competitive
      binding and steric hindrance. On the addition of anticoagulants such as heparin,
      low-molecular-weight heparin, citrate and hirudin, no significant differences
      were observed in plasma supernatant phase FXIIA. However, each anticoagulant
      appears to have a distinct influence on the magnitude of plasma membrane-bound
      FXIIA. On the addition of aprotinin (a kallikrein inhibitor), no significant
      differences were observed in the plasma supernatant FXIIA. In contrast, aprotinin
      appears to significantly reduce membrane-bound FXIIA on Cuprophan and polyamide
      NR, but significantly increase the magnitude of the membrane-bound FXIIA on
      AN69S.

PMID- 8573670
TI  - Controlled release of platelet-derived growth factor using ethylene vinyl acetate
      copolymer (EVAc) coated on stainless-steel wires.
AB  - Controlled delivery of bioactive molecules to modulate or control biological
      processes has a number of clinical applications. The present study reports a
      delivery system which was designed to deliver growth factors locally to a
      fracture site. Ethylene vinyl acetate copolymer (EVAc), bovine serum albumin
      (BSA) and platelet-derived growth factor (PDGF-BB) were combined and coated onto
      a stainless-steel Kirschner wire (K-wire). A K-wire can be used as an
      intramedullary nail in small animal fractures, such as the rat. PDGF-BB
      stimulates thymidine uptake in human bone cell cultures when released from the K
      wire delivery system. BSA release was modified by providing a final coating on
      the K-wire of 10% pure EVAc at the end of the fabrication. Electron microscopic
      examination of the surface of the rods revealed different surface pores on the K
      wires coated with pure EVAc. Differences in porosity and tortuosity may account,
      in part, for the different release kinetics observed.

PMID- 8573671
TI  - Osteoblast adherence and resorption activity of isolated osteoclasts on calcium
      sulphate hemihydrate.
AB  - The adherence of osteoblast-like cells and the resorption activity of isolated
      osteoclasts on calcium sulphate hemihydrate (CSH) was investigated. After a 24 h
      incubation period, alkaline phosphatase staining showed that rat osteoblast-like
      cells ROS 17/2.8 attached on CSH. Neutral red (NR) and tartrate-resistant acid
      phosphatase (TRAP) staining revealed that osteoclasts attached on CSH.
      Furthermore, osteoclasts formed lacunae as revealed by scanning electron
      microscopy. Although the lacunae formed by osteoclasts on CSH were diverse in
      shape and form, the most common type had approximately a circular outline, with a
      well-defined margin similar to those formed on dentine. Less commonly,
      excavations appeared as a discontinuous area of resorbed CSH with the presence of
      a circular zone around the non-resorbed area. Finally, by using 10(-9) M
      calcitonin, evidence was obtained that NR-positive cells were osteoclasts (58.3%
      and 57.66% decrease of NR-positive mouse and rat cells detected on CSH after 24 h
      incubation). However, no inhibition was obtained with 10(-11) M calcitonin. The
      overall number of NR-positive osteoclasts adherent on 256 mm2 CSH was 43 +/- 14
      and 42 +/- 3 for mice and rat, respectively. The overall number of TRAP-positive
      mouse osteoclasts was 67 +/- 12. Acetazolamide (10(-5) M), a carbonic anhydrase
      inhibitor, inhibited the number of adherent NR osteoclasts on CSH by 50.42% and
      41.6% for mouse and rat, respectively. These results indicate that osteoblasts
      attach on CSH and osteoclasts resorb CSH in vitro.

PMID- 8573672
TI  - Detection of alkaline and acid phosphatases around titanium implants: a light
      microscopical and histochemical study in rabbits.
AB  - Alkaline phosphatase (ALP) may play a very important role in the mineralization
      process of bone, while acid phosphatase (ACP) is implicated in bone resorption.
      The aim of the present study was a histochemical characterization of ALP and ACP
      at the bone-implant interface after the insertion of smooth screw-shaped threaded
      titanium implants in rabbit tibia. In the first 3 weeks it was possible to
      observe a very strong positivity in the cytoplasm of osteoblasts near the implant
      surface. These osteoblasts surrounded islands of soft tissue or trabeculated
      woven bone. In the first 4 weeks a large quantity of newly formed bone
      originating from the periosteal and endosteal surfaces was observed; a remodeling
      of the cortical bone was also present. A sharp decrease of the ALP activity was
      observed from the third week onwards, and at 2 months it was possible to observe
      that the ALP and ACP activities were similar, possibly in relation to the
      remodelling of bone. From 2 to 6 months there were no morphological differences
      in the microscopical appearance of the bone around the implants. The bone was
      mature, compact and the new bone had staining features similar to pre-existing
      bone.

PMID- 8573673
TI  - Adsorption of human salivary proteins to titanium powder. I. Adsorption of human
      salivary albumin.
AB  - Titanium (Ti) is among the most widely used implant materials in dentistry today.
      The success of Ti implants is associated with their interactions with the
      surrounding tissues and biological fluids. In the present study, the adsorption
      of salivary proteins to Ti and the effect of calcium (Ca) on this process were
      investigated. Untreated and Ca-treated Ti powders were suspended in human
      clarified whole saliva. After incubation, the supernatant fluid was collected for
      protein analysis. The powders were then washed and resuspended in EDTA to desorb
      proteins from Ti surfaces. Sodium dodecylsulphate polyacrylamide gel
      electrophoresis and Bradford protein assay were conducted to determine the
      concentration and type of proteins that adsorbed onto Ti surfaces. The presence
      of Ca ions enhanced the adsorption of salivary proteins to Ti. A 66 kDa protein,
      identified by immunoblotting as albumin, was found as the main adsorbed salivary
      protein. Adsorption of albumin to Ti pretreated with Ca was significantly greater
      than to native Ti. The Ca-dependent adsorption process was reversed by EDTA. The
      data suggest that salivary albumin is one of the main constituents of a salivary
      biofilm formed on Ti dental implants and its adsorption to Ti surfaces is Ca
      dependent. The presence of albumin on Ti dental implants may affect plaque
      accumulation on the implants and the biocompatibility of Ti implants.

PMID- 8573674
TI  - Titanium-induced enzyme activation on murine peritoneal macrophages in primary
      culture.
AB  - The biological performance of titanium (Ti) particles has been investigated in
      vitro on murine peritoneal macrophages in a primary culture system. The
      ultrastructural study revealed an unchanged morphology with respect to controls
      and the presence of numerous phagocytic vacuoles containing Ti particles as
      confirmed by X-ray microprobe analyses. The activities of beta-glucuronidase,
      acid phosphatase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase
      were determined. All of the enzymes were found to be activated after different
      exposure times to various Ti concentrations. These activations are qualified as
      the consequence of cell defence rather than a significant cytotoxic effect.
      Nevertheless, they indicate a possible inflammatory action of short duration.
      This investigation provides new arguments for the high biological performance of
      Ti.

PMID- 8573675
TI  - Bone changes after experimental osteotomies fixed with absorbable self-reinforced
      poly-L-lactide screws or metallic screws studied by plain radiographs,
      quantitative computed tomography and magnetic resonance imaging.
AB  - The healing of the distal femoral osteotomy fixed with self-reinforced poly-L
      lactide (SR-PLLA) or metallic screws in 16 rabbits was evaluated with plain
      radiographs, quantitative computed tomography and magnetic resonance imaging
      (MRI). At 36 weeks in the metallic fixation there was significantly more external
      callus than in the SR-PLLA fixation. On the metallic fixation side the cortical
      bone mineral density was significantly lower than on the non-operated side at 6
      weeks as well as at 36 weeks. This decrease was not found in the SR-PLLA
      fixation. On the MRI on T1-weighted images a dark zone (signal void), and on the
      T2-weighted images a bright zone (increased signal intensity), was seen
      surrounding the screws, indicating oedema. At 36 weeks these oedematous zones
      were significantly smaller in the SR-PLLA fixation group than in the metallic
      one. The results give indirect evidence towards a more rapid and better osteotomy
      healing with the more physiologically elastic SR-PLLA screws than with the
      metallic screws. Fixation with SR-PLLA screws may prevent stress-protection
      atrophy and weakening of the fixed bone usually caused by the rigid metallic
      fixation.

PMID- 8573676
TI  - An analysis of antigen-antibody binding kinetics for biosensor applications
      utilized as a model system: influence of non-specific binding.
AB  - The influence of non-specific binding on the specific binding of antigen in
      solution to antibody immobilized on a biosensor surface is presented for first-,
      one and a half-, second-, and other order reactions occurring under external
      diffusion-limited conditions. Both single-step and dual-step binding of antigen
      to antibody is considered. For a half-order reaction the value of the ratio of
      non-specific binding to specific binding (alpha) does not affect the rate of
      specific binding since a single curve represents the binding curve for alpha = 0
      to 0.5. An increase in the alpha value leads to a decrease in the rate of binding
      and in the amount of antigen bound specifically to the antibody on the surface
      for first-, one and a half-, and second-order reactions. Also, an increase in the
      reaction order increases the sensitivity of the specific binding to the alpha
      value. An increase in the antigen concentration in solution increases the amount
      and the rate of specific binding for first-, one and a half-, and second-order
      reactions. The introduction of non-specific binding leads to complexities in the
      specific binding of the antigen for the one and half- and second-order reactions
      as the antibody concentration on the surface is varied. When non-specific binding
      is present there is an optimum value of the antibody concentration on the surface
      that yields the maximum rate and amount of antigen specifically bound for one and
      a half- and second-order reactions. Though this optimum amount of antibody
      immobilized on the surface is the same for the one and a half- and second-order
      reactions, it is different for different alpha values. No such complexities are
      observed for first-order reactions. The inclusion of non-specific binding in the
      analysis provides a more realistic picture of the binding of the antigen in
      solution to the antibody immobilized on the surface. The figures that show the
      numerically calculated binding rates for different orders when non-specific
      binding is present, represent the most useful part of the analysis for readers
      who are interested in constructing biosensors, and should assist in the control
      and manipulation of these interactions at the surface. These curves can be used
      to interpret a far from ideal binding of antigen to an immobilized antibody
      surface or vice versa. More-or-less all of the analysis should also be applicable
      to analytical systems that would not be classified as biosensors (that is, immuno
      and receptor assays).

PMID- 8573677
TI  - Molecular dynamics of amphotericin B. II. Dimer in water.
AB  - Molecular dynamics simulations were performed for a dimer of the antifungal
      antibiotic, amphotericin B, in water. In the first step of the work three
      appropriately selected versions of the dimer structure were taken into
      consideration. In each version antibiotic molecules were placed antiparallel with
      polar and ionizable groups outside the hydrophobic core formed by polyene
      chromophores. During short dynamic simulations versions of the dimer structure
      were compared in respect of the energy of dimerization. The highest energy was
      observed for the structure in which polyene chromophores superimposed each other
      as much as possible and this version was subjected to the main simulation. The
      analysis of 66 snapshot geometries stored during 33 ps dynamic trajectory allowed
      us to draw three main conclusions: (i) the relative orientation of the amino
      sugar moiety and chromophore as well as conformation of the antibiotic macrolide
      ring were different in both molecules and could exhibit dynamic changes, (ii) the
      dimer structure exhibited intrinsic asymmetry which could be responsible for
      characteristic circular dichroism spectra of the aggregated form of the
      antibiotic, (iii) relatively high stability of the dimer structure resulted not
      only from hydrophobic interactions between chromophores but also from hydrogen
      bonds networks that were observed around polar terminals of antibiotic molecules.
      Implications of these features of the dimer structure for its susceptibility on
      the ionic state of carboxyl and/or amino groups are also discussed.

PMID- 8573678
TI  - A model for a bistable biochemical trigger of mitosis.
AB  - The activation of maturation promoting factor (MPF, cyclin B/Cdc2), which starts
      mitosis, is modeled as a bistable biochemical switch or trigger. A small, slow
      parameter change can cause an abrupt transition by a saddle-node bifurcation from
      a stable steady state of low activity to one of high activity. The switch is not
      reversed if the parameter change is reversed (hysteresis). The dynamical features
      necessary for this triggering action are the presence of two stable steady states
      (low-activity and high-activity), and one unstable steady state. The key
      biochemical kinetic features of the model are (1) mutual activation by MPF and
      Cdc25, which makes the activation of MPF effectively autocatalytic, and (2)
      binding of MPF by Suc1, which inhibits MPF autocatalysis and stabilizes the low
      activity steady state until the amount of MPF begins to approach or exceed
      stoichiometrically the amount of Suc1, then allows strong autocatalysis and full
      activation. The special virtues of bistable triggering, and the general types of
      biochemical mechanism which can produce it, are discussed.

PMID- 8573679
TI  - A comparison of the surface activity of the fungal hydrophobin SC3p with those of
      other proteins.
AB  - The fungal hydrophobin SC3p, a protein secreted by Schizophyllum commune, has
      become known to form SDS-insoluble layers and to change the physico-chemical
      properties of an interface. In this study, the surface activity of SC3p was
      studied by determining the interfacial tensions gamma iv and gamma sl during
      adsorption of SC3p at both the liquid-vapour and the solid-liquid interface
      utilizing the in situ technique axisymmetric drop-shape analysis by profile. To
      this end, protein solution droplets were put on the solid fluoroethylene
      propylene-Teflon. At the liquid-vapour interface, SC3p caused a large decrease of
      gamma iv from 72 to 43 mJ m-2 at the concentration of 0.1 mg ml-1. At the solid
      liquid interface, gamma sl was slightly decreased, whereas the contact angle
      theta increased, indicating an increase in hydrophobicity of FEP-Teflon, which is
      unique among the proteins studied so far. Earlier findings indicated a decrease
      in hydrophobicity of Teflon upon adsorption of SC3p, but this was after a washing
      and drying step. In order to reconcile these findings with those of the present
      study, adsorption of SC3p to hydrophobic surfaces is suggested to occur in
      bilayers. The second layer is supposed to be less strongly adsorbed than the
      first layer and can be easily removed by washing.

PMID- 8573680
TI  - Conformational changes of E. coli RNA polymerase during transcription initiation.
AB  - Escherichia coli RNA polymerase-promoter complex undergoes a multistep process to
      initiate transcription. We have employed fluorescence spectroscopic approaches to
      detect the conformational states of the enzyme during this multistep process. A
      fluorescence assay based on the measurement of fluorescence of free and promoter
      bound enzyme as a function of temperature within the range of 4 to 37 degrees C
      showed that, starting with initial 'closed complex', there are conformationally
      two distinct intermediate states of the polymerase till it attains the final form
      required for transcription initiation. The equilibrium from closed complex (RPc)
      to open complex (RPo) consists of at least the following two intermediate
      complexes: [formula: see text] Higher order structure of RNAP in each of these
      complexes was probed by means of measurement of accessibilities of the tryptophan
      fluorophores to the acrylamide. In the next part of the study, TbGTP, a
      fluorescent substrate, has been used to probe the state of active site in the
      enzyme for the complexes RPc, RPi1, RPi2 and RPo, respectively. From the
      comparison of changes in the parameters such as, fluorescence polarization
      anisotropy of TbGTP and its accessibility to the neutral quencher, acrylamide, in
      free and promoter-bound enzyme, we have further substantiated the first part of
      our results. Together these results suggest that formations of RPc and RPi1 do
      not involve radical conformational changes in the enzyme, while the enzyme
      undergoes major change in conformation in the steps RPil-->RPi2 and RPi2-->RPo.
      The strong tryptophan promoter cloned in plasmid pDR720 was chosen as a model
      promoter in these studies.

PMID- 8573681
TI  - Interactions of alpha-chymotrypsinogen A with alkylureas.
AB  - Solvation of alpha-chymotrypsinogen A (alpha-ctg A) in aqueous urea, methylurea,
      N,N'-dimethylurea and ethylurea was studied by density measurements. From the
      densities at constant molality and at constant chemical potential the
      preferential solvation parameters were determined. In urea and methylurea
      preferential solvation was observed, whereas in N,N'-dimethylurea and ethylurea
      at higher concentration water is preferentially bound. From preferential
      solvation data Gibbs free energy of transfer of alpha-ctg A from water to urea
      and alkylurea solutions were calculated. Since the enthalpies of transfer were
      determined previously, the entropies of transfer could also be obtained so that a
      complete thermodynamic description is available. An attempt is made to interpret
      the values of the thermodynamic quantities in terms of various interactions
      involved in solvation as well as to calculate the exchange constant by using the
      model of weak interactions. In solvation of alkylureas the hydrophobic nature of
      the alkyl groups is clearly reflected.

PMID- 8573682
TI  - Two-photon induced fluorescence of linear alkanes; a possible intrinsic lipid
      probe.
AB  - We measured the fluorescence emission spectra and intensity decays of the linear
      alkane tetradecane when excited at 300 nm by two-photon excitation. The
      unquenched lifetime of tetradecane in neat solution is near 4.4 ns. The emission
      of tetradecane centered at 210 nm is collisionally quenched by oxygen, n-propanol
      and water. These results suggest that aliphatic groups in non-polar environments
      can display good fluorescence, and that the aliphatic side chains of detergents
      and lipids may serve as an intrinsic fluorescent probe of micelles and bilayers.

PMID- 8573683
TI  - A population pharmacokinetic study of alminoprofen penetration into synovial
      fluid.
AB  - The pharmacokinetics of alminoprofen in plasma and synovial fluid (SF) at steady
      state (300 mg t.i.d.) was studied in 45 patients with knee effusion. Plasma and
      SF samples, one each per patient, were obtained. Six groups were made according
      to the time of sampling after ingestion of the 13th dose: 1 h (n = 7), 2 h (n =
      7), 4 h (n = 7), 6 h (n = 10), 8 h (n = 6), 12 h (n = 8). A three-compartment
      model was used to describe alminoprofen kinetics in plasma and SF, with two
      parameterizations, a 'classical' and a 'physiological' one. The non-linear mixed
      effect model approach was used to estimate the mean and variance of the
      pharmacokinetic parameters. The mean +/- SE of the estimates (coefficient of
      variation of interindividual variability as a percentage) were volume of
      distribution, 11.0 +/- 1.711 (12%); elimination rate constant, 0.236 +/- 0.025 h
      1 (18%); absorption rate constant 2.80 +/- 0.31 h-1 (464%), clearance of influx
      into SF, 0.29 +/- 0.14 mL min-1; clearance of efflux into plasma, 0.56 +/- 0.25
      mL min-1. These two clearances were not significantly different, which indicates
      that passive diffusion occurs in both directions. The mean +/- SD alminoprofen
      concentration versus time curve in plasma and SF at steady state was simulated
      and showed that the mean +/- SD maximal concentration in SF was 8.1 +/- 6.3 mg L
      1 and was obtained 4 h after dose administration.

PMID- 8573684
TI  - Pharmacokinetics of HI-6 and atropine in anaesthetized pigs after administration
      by a new autoinjector.
AB  - A newly developed autoinjector (Astra Tech, Sweden) containing 500 mg HI-6 and 2
      mg atropine sulphate was tested in anaesthetized normal pigs. The
      pharmacokinetics and pharmacodynamics of the drugs after administration by the
      autoinjector were compared with those after conventional needle and syringe
      delivery intramuscularly and intravenously. Cardiopulmonary parameters were
      monitored and serum concentrations of oxime, atropine, and acetylcholinesterase
      were determined in blood samples taken at intervals over a 6 h period
      postinjection. After injection in anaesthetized pigs, both HI-6 and atropine were
      absorbed rapidly and completely from the injection site. Therapeutic serum
      concentrations of HI-6, arbitrarily taken as 4 micrograms mL-1, were reached
      within 1 min of intravenous and autoinjector administration, and within 5 min of
      intramuscular injection. The concentrations remained above this level for 3-4 h.
      There were no significant changes in acetylcholinesterase activity, mean arterial
      blood pressure, or respiration frequency after injection of HI-6 and atropine
      sulphate. The heart rates increased significantly after administration of the two
      drugs (cardioacceleration defined as > or = 5% increase in heart rate),
      regardless of the technique employed. Our results show that HI-6 and atropine
      sulphate can be given intramuscularly by the new autoinjector with the same
      effectiveness and speed as when given intravenously. Irrespective of the
      injection technique, no overt signs of toxicity were observed at the drug
      concentrations used.

PMID- 8573685
TI  - Pharmaceutical and biological properties of doxorubicin encapsulated in liposomes
      (L-ADM): the effect of repeated administration on the systemic phagocytic
      activity and pharmacokinetics.
AB  - We investigated the biodistribution and antitumour activity of doxorubicin (ADM)
      encapsulated in liposomes (L-ADM) after two administrations in tumour bearing
      mice. The effect of the first administration on phagocytic activity was also
      examined. The biodistribution of L-ADM after the second dosing at an interval of
      4d was remarkably different from that after the first. The concentration of ADM
      in plasma and tumour after the second injection was higher, but that in the liver
      was lower than after the first administration. This decrease in distribution to
      the liver is thought to have contributed to the difference in the biodistribution
      characteristics of L-ADM. With regard to antitumour effect, the activity was
      similar between L-ADM and a solution of ADM (F-ADM). To investigate the effect of
      the first administration of L-ADM on biodistribution, systemic phagocytic
      activity was measured after the injection of F-ADM, L-ADM, or 'empty' liposomes
      not containing ADM. F-ADM and L-ADM (7.5 mg ADM/kg body weight) reduced
      phagocytic activity to approximately 50% and 30% of control, respectively. This
      finding suggests that entrapment of ADM in liposomes enhances both the
      distribution of the drug to the reticuloendothelial system (RES) and its
      suppressive effect on RES activity. These results indicate that the decrease in
      RES activity by L-ADM must be considered in estimation of the pharmacokinetics,
      antitumour activity, and toxicity of L-ADM in clinical use when given by repeat
      administration or used in combination with other antitumour agents.

PMID- 8573686
TI  - Pharmacokinetic parameters of antipyrine in dog after hepatectomy.
AB  - Pharmacokinetic studies with antipyrine were carried out on beagle dogs to
      determine the consequence of hepatectomy on hepatic drug metabolizing capacity,
      the rate of hepatic regeneration, and the possible beneficial effect of
      hepatocellular transplantation. The drug (250 mg) was administered by short IV
      infusion in three groups of dogs (first group, 65% hepatectomy; second group, 65%
      hepatectomy with hepatocyte transplantation; third group 80% hepatectomy).
      Pharmacokinetic parameters of antipyrine were evaluated before surgery and within
      10 d after surgery. Blood samples were taken at frequent intervals after drug
      administration and antipyrine was assayed in plasma by a specific HPLC method
      with UV detection. Before surgery, the mean elimination half-life was about 1.1 h
      and total clearance averaged 6 L h-1. In dogs with 65% hepatectomy, no
      statistical differences in pharmacokinetic parameters of antipyrine appeared
      before or after surgery. When 65% hepatectomy was associated with hepatocyte
      transplantation, a significant increase in elimination half-life and a
      significant decrease in total clearance were observed. The same statistical
      differences in the pharmacokinetic parameters were observed in the group with 80%
      hepatectomy. Transplantation of isolated hepatocytes into the spleen did not
      correct hepatocellular insufficiency. In this study, numerous laboratory tests
      were performed. A significant correlation was found between serum albumin,
      cholesterol, factor V, ALAT, total bilirubin, and ratio of amino acids and the
      pharmacokinetic parameters of antipyrine.

PMID- 8573687
TI  - Pharmacokinetics of terbinafine and of its five main metabolites in plasma and
      urine, following a single oral dose in healthy subjects.
AB  - The plasma pharmacokinetics, and the urinary excretion, of terbinafine and its
      five main metabolites have been investigated after a single oral dose
      administration of 125 mg to 16 healthy subjects. In plasma, the highest
      concentrations are observed for the two carboxybutyl metabolites, with a
      predominance for the carboxybutylterbinafine. For this metabolite, as compared to
      terbinafine, the Cmax and AUC are 2.4 and 13 times higher respectively. The
      demethylterbinafine presents a plasma profile close to that of terbinafine. The
      two hydroxy metabolites are only found as glucuronide and are of minor
      importance. The apparent terminal half-lives of terbinafine, demethylterbinafine,
      and the two carboxy metabolites appear to be similar (approximately 25 h). As
      compared to the plasma concentration of total radioactivity observed after a
      single oral administration of the same dose of 14C-terbinafine, the parent drug
      and these five metabolites, account for more than 80% of the total radioactivity
      in plasma over the 0-48 h interval following administration. In urine, the major
      metabolite is demethylcarboxybutylterbinafine, which amounted to about 10% of the
      administered dose. Terbinafine and demethylterbinafine are only excreted as trace
      amounts in urine. Carboxybutylterbinafine and the two hydroxy metabolites are
      excreted in the range of 0.5-2% either as glucuronides or free. Urinary excretion
      over the 0-48 h interval of terbinafine and of the five metabolites amounted to
      about 14% of the administered dose. This is far below the level of total
      radioactivity measured in urine over the same interval (approximately 57%), after
      administration of 14C-terbinafine. This shows in contrast to plasma, that
      numerous other metabolites are present in urine.

PMID- 8573688
TI  - The effect of aging on the pharmacokinetics of nalbuphine in rabbits.
AB  - For the purpose of selecting an animal model for the study of the aging effect on
      the pharmacokinetics of nalbuphine, the pharmacokinetic properties in young and
      in aged rabbits were reported. Thirty-one healthy New Zealand white rabbits
      ranging in ages (mean) from three months to 43 months (six three months old,
      group I; nine eight months old, group II; nine 18 months old, group III; and
      seven 43 months old, group IV) were included in the study. After intravenous
      bolus injection of nalbuphine (10 mg kg-1) to each rabbit, plasma samples were
      collected and analysed for nalbuphine by a high-performance liquid chromatography
      method. The plasma concentration-time data regarding nalbuphine were successfully
      fitted to a linear two-compartment open model. The elimination half-life of
      nalbuphine in rabbits increased significantly with age. Consequently, clearance
      decreased significantly with age. The parameter AUCO-affinity, which is derived
      from dose/clearance, increased significantly with age. The effect of aging on the
      pharmacokinetics of nalbuphine in rabbits is quite similar to that in humans.
      From the present study, it is concluded that rabbits may be suitable for the
      study of aging effects on the pharmacokinetics of nalbuphine.

PMID- 8573689
TI  - Protein binding of sotalol enantiomers in young and elderly human and rat serum
      using ultrafiltration.
AB  - The protein binding of sotalol (STL) enantiomers was evaluated using an
      ultrafiltration technique with serum from young (32 +/- 2 years, n = 5) and
      elderly (73 +/- 6 years, n = 5) male and female humans, and young (8 weeks, n =
      4) and elderly (60 weeks, n = 3) male Sprague-Dawley rats. Serum samples were
      collected and immediately frozen at -20 degrees C. Within 1 week, the serum
      samples were thawed at room temperature, and adjusted to pH 7.4 using 0.05 M
      phosphate buffer, pH 5.0. Aliquots were spiked with 250 ng mL-1 and 500 ng mL-1
      of each STL enantiomer, placed in ultrafiltration sets (Microsep, 30K molecular
      weight cut-off), capped, equilibrated to 37 degrees C, and centrifuged at 1850g
      for 1.5 h at 37 degrees C. Aliquots of ultrafiltrate and unspun serum were
      analysed for STL enantiomer concentration using a stereospecific HPLC assay. In
      all groups, bound fraction was less than 7% for both STL enantiomers. There were
      no significant differences in bound fraction between groups, or between
      enantiomers. Adsorption of STL enantiomers to the ultrafiltration device and
      membrane, evaporative loss of serum samples during centrifugation, and protein
      concentration in each ultrafiltrate sample were all negligible. It is concluded
      that the binding of STL in human and rat serum at therapeutic concentrations and
      physiological temperature and pH is negligible and non-stereoselective.

PMID- 8573690
TI  - Disposition kinetics of aditoprim in two monkeys in comparison to other mammalian
      species.

PMID- 8573691
TI  - Modeling insect olfactory neuron signaling by a network utilizing disinhibition.
AB  - A male moth locates a conspecific female by detecting her sexual-pheromone blend.
      This detection is carried out in the antennal lobe, the first stage of olfactory
      information processing, where local inhibitory neurons and projection (relay)
      neurons interact. Antennal-lobe neurons exhibit low-frequency (< 10 Hz)
      background activity and bursting (> 100 Hz) activity in response to pheromone
      stimulation. We describe this behavior by a realistic biophysical neuron model.
      The bursting behavior of the model is the result of both intrinsic cellular
      properties and network interaction. A slowly activating and inactivating calcium
      channel provides a depolarizing current for bursting and disinhibition is shown
      to be a feasible network mechanism for triggering this calcium channel. Small
      neural networks utilizing disinhibition are presented with local neurons
      intercalated between receptor and projection neurons. The firing behaviors of
      projection neurons in response to stimulation by the pheromone blend or its
      components are in accordance with experimental results. This network architecture
      offers an alternative view of olfactory processing from the classical
      architecture derived from vertebrate studies.

PMID- 8573692
TI  - Computer-aided analysis of potential transcription-factor binding sites in the
      rabbit beta-casein gene promoter.
AB  - Computer analysis of putative cis- and trans-regulatory sequences in the promoter
      region of the rabbit beta-casein gene is described. Nucleotide sequences up to
      2096 bp upstream of the initiation site were compared to known consensus
      sequences of both ubiquitous and specific transcription factor motifs as well as
      to those described as characteristic for milk protein genes. Our analysis
      demonstrated that 5 independent motifs described for milk protein gene promoters
      exist. Four of them--'Groenen structure', 'Yu-Lee' 1 and 6 sequence and 'Oka box
      A'--were found in the beta-casein gene promoter; surprisingly, no typical milk
      box was found. More than one hundred and fifty putative binding motifs were
      found, representing 56 various consensus sequences. These sequences are located
      both inside and outside structures typical of milk protein gene promoters and
      include sequences homologous to mammary gland specific, hormone specific and
      ubiquitous transcription factors. Our analysis suggests that milk protein gene
      promoters can bind many transcription factors and assure complex regulation by
      hormonal and tissue specific factors.

PMID- 8573693
TI  - General linear compartment model with zero input: I. Kinetic equations.
AB  - The derivation of kinetic equations is described for n-compartment linear models,
      in which the substance may be simultaneously introduced into one or more
      compartments at t = 0 and eliminated from any compartment. For a given zero
      input, general formulas are derived which describe the amount of tracer in any of
      the compartments as a function of time and the model parameters. New algorithms
      have been developed which allow the expression of the kinetic equations.

PMID- 8573694
TI  - General linear compartment model with zero input: II. The computerized derivation
      of the kinetic equations.
AB  - The final equations obtained in the first article of this series describing the
      concentrations of substances in any of the compartments of a model are here cast
      in an easily programmable form. A computer program with an easy input method and
      the ability to expand all of the coefficients in the kinetic equations in terms
      of the model parameters has been developed. The program has been written in the
      BASIC language.

PMID- 8573695
TI  - General linear compartment model with zero input: III. First passage residence
      time of enzyme systems.
AB  - In this paper, we present an alternative procedure to derive the residence times
      of enzyme and compartment systems. This procedure allows to express the residence
      time by a general, symbolic and simplified formula relating it directly with the
      rate constants. It is applicable to any enzyme reaction scheme which can be
      formulated as a set of first-order or pseudo-first order interconversions,
      without any other restriction. A computer program has been developed that greatly
      facilitates the task of the residence time derivations. The above analysis was
      extrapolated to any linear compartment model.

PMID- 8573696
TI  - A comparison of methods for self-adaptation in evolutionary algorithms.
AB  - Evolutionary algorithms, including evolutionary programming and evolution
      strategies, have often been applied to real-valued function optimization
      problems. These algorithms generally operate directly on the real values to be
      optimized, in contrast with genetic algorithms which usually operate on a
      separately coded transformation of the objective variables. Evolutionary
      algorithms often rely on a second-level optimization of strategy parameters,
      tunable variables that in part determine how each parent will generate offspring.
      Two alternative methods for performing this second-level optimization have been
      proposed and are compared across a series of function optimization tasks. The
      results appear to favor the approach offered originally in evolution strategies,
      although the applicability of the findings may be limited to the case where each
      parameter of a parent solution is perturbed independently of all others.

PMID- 8573697
TI  - Molecular neural network devices based on non-linear dynamic media: basic
      primitive information processing operations.
AB  - Basic primitive image-processing operations performed by molecular and
      biomolecular dynamic media functioning in the oscillating mode are discussed.
      These operations have rather high computational complexity and can be considered
      as simulations of human vision capabilities.

PMID- 8573698
TI  - The evolution of understanding: a genetic algorithm model of the evolution of
      communication.
AB  - Much animal communication takes place via symbolic codes, where each symbol's
      meaning is fixed by convention only and not by intrinsic meaning. It is unclear
      how understanding can arise among individuals utilizing such arbitrary codes, and
      specifically, whether evolution unaided by individual learning is sufficient to
      produce such understanding. Using a genetic algorithm implemented on a computer,
      I demonstrate that a significant though imperfect level of understanding can be
      achieved by organisms through evolution alone. The population as a whole settles
      on one particular scheme of coding/decoding information (there are no separate
      dialects). Several features of such evolving systems are explored and it is shown
      that the system as a whole is stable against perturbation along many different
      kinds of ecological parameters.

PMID- 8573699
TI  - Slower aging in women: a proposed evolutionary explanation.
AB  - Differential female longevity is so far unexplained in evolutionary terms. The
      theory of evolutionarily necessary aging which goes back to Wallace appears to be
      up to the task. In this theory, aging minimizes competition between forebear and
      offspring. The aging equation which is implicit contains the well-known empirical
      Gompertz law as a special case. Moreover, its parameters are automatically sex
      specific. It is shown that the slower aging of the female members of two species
      of mammals, humans and sperm whales, can be 'predicted' on the basis of this
      equation. A prediction of effective human monogamy under archaic conditions is
      obtained as a corollary. The analogous if opposite prediction for sperm whales
      (strong promiscuity) is empirically testable.

PMID- 8573700
TI  - Magnetic field effects on biomolecules, cells, and living organisms.
AB  - This article surveys three major areas of biomagnetic research: (a) the magneto
      orientation effect; (b) the role of the geomagnetic field in bird orientation and
      navigation; and (c) the biological effects of extremely low-frequency magnetic
      fields. The magneto-orientation effect is caused by diamagnetic anisotropy of
      highly ordered biological structures, such as visual photoreceptor and
      chloroplast membranes, in a homogeneous magnetic field of about 10 kG. While it
      is not possible to orient the individual constituent molecules with such a field
      because of thermal fluctuation, these ordered structures can be oriented as a
      whole by virtue of summing the anisotropy over a large number of mutually
      oriented molecules. While the magneto-orientation effect seems to require the use
      of unphysiologically strong magnetic fields, certain birds apparently have highly
      sensitive sensors to detect the geomagnetic field for the purpose of orientation
      and navigation. However, the advances in this latter field were made mainly in
      the behavioral studies; the magneto-sensors the the neural mechanisms remain
      elusive. A number of candidates of the sensors are evaluated. We suggest that
      pecten oculi, which is unique to avian eyes, should not be overlooked for its
      possible role as a magneto-sensor based on the magneto-orientation effect. Birds
      primarily use a static (DC) magnetic field for orientation, but recent
      investigations indicate that weak alternating (AC) magnetic fields with extremely
      low frequency (ELF) may have hazardous health effects. Such reports are often
      received with skepticism, because the effects usually involve magnetic energies
      that are less than the kT energy. However, some of the in vitro studies yield
      experimental results that are too significant to be ignored. Here, we propose an
      argument to explain why low-level magnetic fields can be detected without being
      overshadowed by thermal noises. Relevance of biomagnetic research to the
      development of biosensors and novel computational paradigms is also discussed.

PMID- 8573701
TI  - Chou-Fasman conformational amino acid parameters and the genetic code.
AB  - It was found that the distribution of Chou-Fasman P alpha conformational
      parameters within the genetic code (arranged into the one-step mutation ring) may
      be described by a quite simple trigonometric function of mutational angle. The
      mutational angle is defined as k pi/32, where k is a number of codons count from
      i under consideration to k. The principal eight-codon periodicity defines the P
      alpha-genetic code correspondence, but the other perioditicies seem also to
      modulate the principal function. The eight-codon periodicity finds the
      explanation in the regular changes of third bases of successive codons. These
      changes appear in the order; C,U,A,G,G,A,U,C, assigning eight maxima and eight
      minima of P alpha curve. The experimental P alpha values fit well the dependence
      found, except proline, the amino acid which breaks the regular eight-codon P
      alpha periodicity. The analysis of dependence obtained suggest that, in agreement
      with the hypothesis of Jukes (1973), arginine CGR and AGR codons could be in an
      earlier genetic code used for coding of ornithine.

PMID- 8573702
TI  - The treatment of visual neglect using feedback of eye movements: a pilot study.
AB  - Feedback of eye movements was evaluated as a treatment for visual neglect in
      right hemisphere stroke patients. Patients with visual neglect identified on the
      Behavioural Inattention Test (BIT) were randomly allocated to two groups. One
      group (n = 9) was treated for 2 h 40 min a week for 4 weeks, by wearing glasses
      which provided a reminder bleep if patients failed to move their eyes to the left
      in a 15 s interval. The control group (n = 9) received no treatment for their
      visual inattention. Comparison of the groups after 4 weeks treatment and a
      further 4 weeks follow-up showed no significant difference either in eye
      movements or on the BIT. However, there was a trend towards a difference between
      eye movements in the two groups at 8 weeks, suggesting treatment may have
      influenced eye movements without changing neglect.

PMID- 8573703
TI  - A geriatric day hospital in Hong Kong: an analysis of activities and costs.
AB  - A survey of the activities of a geriatric day hospital in Hong Kong was carried
      out. It revealed that alternative modalities of hospital-based treatment were
      impractical and difficult to organize. Most patients and their carers were
      satisfied with the day hospital service, and the main area for improvement was in
      transportation. Costs of day hospital treatment were also calculated, and were
      found to be cheaper than an equivalent period of in-patient rehabilitation or out
      patient therapy.

PMID- 8573704
TI  - The effect of body position on bioelectrical resistance in individuals with
      spinal cord injury.
AB  - The purpose of this study was to determine the effect of four different body
      positions on the resistance of the human body as assessed by Biodynamics Model
      310 Body Composition Analyzer in a healthy population (Group A, n = 69) and long
      term spinal cord injured (Group B, n = 13). Group A were tested in four body
      positions: supine, half-lying, standing and sitting in a wheelchair, while Group
      B were tested in supine and sitting positions. Testing order was randomized. A
      one-way repeated measures analysis of variance and a paired t-test demonstrated
      significant differences between position (p < 0.0001, Group A; p < 0.01, Group B
      respectively). In both groups, the greatest reduction in resistance was
      demonstrated for the sitting position. These differences were similar for both
      groups, as demonstrated by covariant analysis. Regression analysis demonstrated
      that supine resistance can be accurately predicted (R2 = 0.98) from assessments
      in a wheelchair. Such data transformations may be indicated where supine
      positioning is problematic or when wheelchair assessment procedures are more
      appropriate.

PMID- 8573705
TI  - Cardiovascular adjustments and perceived exertion during exercise on the BAPS
      board.
AB  - The Biomechanical Ankle Platform System (BAPS) is widely used in medical
      rehabilitation; however, the cardiovascular demand and subjective acceptability
      of the BAPS rehabilitation exercise are presently not documented. The purpose of
      this study was to evaluate the pattern and magnitude of the cardiovascular
      adjustments and rating of perceived exertion (RPE) during an acute bout of
      exercise on the wobble board. Twenty healthy (mean age 24.2 +/- 2.9 years old)
      subjects exercised for 10 min each on the BAPS board on two different occasions.
      One test was performed using the small hemisphere board while the other test was
      performed with the large hemisphere board. The subjects' heart rate (HR), blood
      pressure (BP), cutaneous blood flow (BF), skin temperature (ST) at the ankle
      joint, local and overall RPE responses were monitored at specific time periods.
      Micro-circulation, skin temperature and heart rate were monitored with the
      LaserFlo Blood Perfusion Monitor, the Physitherm thermocouple and the Cardiotach
      recorder, respectively. The subjects' rating of perceived effort during exercise
      was obtained with a 15-point category scale. The result showed significant
      perturbation of the cardiovascular system during the BAPS exercise. Similarly,
      both local and overall RPE increased as the duration of exercise increased. The
      BF and RPE during the large hemisphere exercise session were significantly higher
      than the small hemisphere session. The subjects' subjective report following the
      exercise suggests the need for caution in the use of the BAPS board exercise for
      frail patients and also patients with lower extremity joint pathologies.

PMID- 8573706
TI  - The long-term outcome of upper limb amputees treated at a rehabilitation centre
      in Sydney, Australia.
AB  - A follow-up study by questionnaire or interview has been made of the 27
      respondents of 41 upper limb amputees (66%) treated at the Royal South Sydney
      Hospital between 1981 and 1990. Prosthetic use of 8 h/day or more was 37% and
      occasional use was 18.5%. The prosthetic users were more likely to be distal
      amputees. The reason for the low level of prosthetic use is not known. The
      majority of non-users discarded prostheses after leaving their rehabilitation
      programme. Occupational changes were made by 72% of the amputees. The
      unemployment rate at follow-up was similar to the rest of the community, which is
      a better outcome than 25 years ago. Activities of daily living had been affected
      in all patients, but to a lesser extent in prosthetic users. Leisure pursuits
      were changed in 70% of patients, with these activities being more sedentary and
      indoor in nature. Of the 18 car drivers, 15 drove automatic cars with
      modifications. Phantom pain was experienced by 16 of the respondents (59%) and
      stump pain was experienced by seven. Only 26% used medication or alcohol for the
      pain. Pain did not affect prosthetic use or functional ability.

PMID- 8573707
TI  - Introduction of integrated care pathways for patients with multiple sclerosis in
      an inpatient neurorehabilitation setting.
AB  - Rehabilitation of progressive neurological disorders such as multiple sclerosis
      poses particular problems, and clear setting of goals and clinical audit are
      essential for effective management. Integrated care pathways (ICPs) offer a
      unique opportunity to document and audit the rehabilitation process. This
      preliminary study has shown that ICPs are useful in both assessing process and
      auditing goals. Their introduction has led to the identification of the key
      worker role within the neurorehabilitation unit (NRU), and has provided an
      opportunity to increase the participation of patients and carers in the
      rehabilitation process. Continuing refinement of the pathway is necessary, and
      its application to other neurological disorders such as cerebrovascular accident
      may be appropriate.

PMID- 8573708
TI  - Four case reports illustrating the contribution of intensive cognitive
      rehabilitation in patients neuropsychologically handicapped as a result of brain
      damage.
AB  - The authors describe the principles and functioning of a 7-week course of
      interdisciplinary treatment for small groups of patients with cognitive and
      behavioral difficulties resulting from brain damage. The programme is intended
      for patients with less severe physical disability. It outlines a programme of
      individual, practically oriented workshops and of more theoretical group sessions
      working on cognitive and communications handicaps. The work is based on
      conceptual explanations, coping strategies and training techniques. The
      neurological and neuropsychological consequences of four subjects accepted on
      such a programme are presented, as well as some of the principles of treatment
      used for these patients. The efficacy of such programmes is discussed, given the
      classical post-traumatic picture of brain-injured patients. The programme
      consists of 1 week of evaluation and 6 weeks of therapeutic sessions.

PMID- 8573709
TI  - The Functional Independence Measure: a comparative validity and reliability
      study.

PMID- 8573710
TI  - Third annual William L. McGuire Memorial Lecture. "Studies on the estrogen
      receptor in breast cancer"--20 years as a target for the treatment and prevention
      of cancer.
AB  - In 1973, McGuire and Chamness (In: O'Malley BW and Means AR (ed) Receptors for
      Reproductive Hormones, Plenum Press) summarized their work on the estrogen
      receptor in animal and human breast tumors, and in so doing described a target
      for therapeutic intervention. At that time there were no clinically useful
      antiestrogens, but the subsequent development of tamoxifen for breast cancer
      therapy has revolutionized the approach to treatment. Long-term adjuvant
      tamoxifen adjuvant therapy (i.e., greater than one year) has proven efficacy to
      enhance the survival of breast cancer patients. In addition, because there is an
      associated 40% decrease in contralateral breast cancer during adjuvant tamoxifen
      therapy and tamoxifen maintains bone density and reduces fatal myocardial
      infarction, clinical trials to test the worth of tamoxifen as a preventive for
      breast cancer in high risk women have started in the United States, United
      Kingdom, and Italy. Initial concerns that long-term tamoxifen causes endometrial
      cancer have been placed in perspective and analyzed by a review of the
      literature. Tamoxifen only doubles the normal risk of detecting endometrial
      cancer (i.e., to 2 per 1,000 tamoxifen-treated women per year), and 80% of these
      cases are early stage, good prognosis disease. Annual gynecological examinations
      and education are essential to provide reassurance for patients. The success of
      tamoxifen has encouraged the development of new antiestrogens to exploit the
      estrogen receptor as a therapeutic target. Droloxifene and TAT-59 mimic the
      metabolite 4-hydroxytamoxifen in having a high affinity for the estrogen receptor
      (Jordan et al, J Endocrinol 75:305, 1977). These drugs appear to have a
      pharmacological profile similar to tamoxifen. In contrast, the new pure
      antiestrogens have a distinct mechanism of action and will be valuable either as
      a first line therapy for advanced breast cancer or as a second line endocrine
      therapy after the failure of long-term adjuvant tamoxifen therapy. Finally, a new
      strategy is being developed to exploit the target site specific action of
      antiestrogens. Raloxifene, an antiestrogen with high affinity for the estrogen
      receptor but only weak estrogenicity for the uterus, prevents rat mammary
      tumorigenesis and maintains bone density. The drug is to be evaluated as a
      treatment for osteoporosis, but may also prevent the development of breast and
      endometrial cancer in a broad group of treated subjects. The identification of
      the estrogen receptor as a target for therapeutic opportunities has proved to be
      extremely beneficial for the control of breast cancer and has the added potential
      to control osteoporosis and coronary heart disease in women.

PMID- 8573711
TI  - Plasma changes in breast cancer patients during endocrine therapy--lipid
      measurements and nuclear magnetic resonance (NMR) spectroscopy.
AB  - Side-effects following long-term endocrine therapy might have clinical
      implications. The aim of this study was to study potential methods to detect
      effects on plasma induced by hormonal therapies. The composite methylene
      (chemical shift between 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) aliphatic peaks of
      the 1H magnetic resonance spectrum (500 MHz) were analysed in consecutive plasma
      samples of 23 cancer patients drawn before and during treatment with hormonally
      acting drugs. The aliphatic peaks were analyzed for line width at half-height and
      then averaged. In addition, 13C magnetic resonance spectroscopy (125 MHz)
      analyses were done in selected patients. The blood samples were analyzed for
      triglyceride, cholesterol, apolipoprotein A1 (apo A1), and apolipoprotein B (apo
      B) levels. The methylene line width increased significantly after 9 weeks of
      tamoxifen (41.4 vs. 37.6 Hz). A trend of differences was observed in the
      saturated part of the 13C magnetic resonance spectrum. A significant decrease in
      total cholesterol (mean decrease, 13%), increases in apo A1 (9%) and in the ratio
      of apo A1 to apo B (28%), but unchanged total triglycerides were found,
      indicating a decrease in LDL and increase in HDL lipoproteins in these patients
      following tamoxifen therapy. During dose escalation with the aromatase inhibitor
      exemestane, the methylene line width seemed to decrease (31.9 vs 38.8 Hz, at 12
      weeks and baseline, respectively). Significant decreases in total (13%) and HDL
      (32%) cholesterol, apo A1 (25%), and total triglyceride (16%) levels were found
      during the same interval. The apo A1/apo B ratio decreased by 25%. For patients
      on dexamethasone, the proton aliphatic line widths increased one day after the
      initiation of therapy. The changes in line shape observed during dexamethasone
      therapy indicated lower levels of triglyceride-rich relative to triglyceride-poor
      lipoproteins, consistent with results from the lipid analyses. In conclusion,
      nuclear magnetic resonance spectroscopy might have potential to detect effects on
      plasma induced by endocrine therapy. The lipid analyses in these patients were in
      support of the changes in lipid profile as evaluated by nuclear magnetic
      resonance spectroscopy.

PMID- 8573712
TI  - Tamoxifen elicits rapid transmembrane lipid signal responses in human breast
      cancer cells.
AB  - The antiestrogen tamoxifen competes with estrogen for receptor occupancy,
      although reports indicate that not all effects of tamoxifen are mediated via this
      specific interaction. In the present study we sought to determine whether
      tamoxifen can initiate transmembrane lipid signals. Lipid signaling is a
      prominent mode by which hormones, growth factors, and phorbol diesters transduce
      messages. Using the human mammary carcinoma cell line MDA-MB-231, phospholipid
      metabolism was analyzed in cells prelabeled with 3H-fatty acid. After short-term
      (10 min) exposure to tamoxifen (10 microM), cellular phosphatidic acid (PA)
      increased by approximately 50%. Dose-response kinetics for PA formation were
      obtained over a tamoxifen range of 2.5-20 microM. Treatment of MDA-MB-231 cells
      with phorbol diester (12-O-tetradecanoylphorbol-13-acetate, TPA) also elicited PA
      generation (60% above control). Interestingly, addition of tamoxifen, a purported
      protein kinase C inhibitor, to TPA-treated cells, caused further increase in PA
      (approximately 100% above control). PA, a second messenger lipid produced upon
      effector-receptor coupling, shares a prominent role in signal transduction events
      that govern cellular proliferation. It is therefore suggested that some actions
      of tamoxifen are mediated by promoting production of second messenger lipids that
      elicit transmembrane signal transduction cascades. This view is in line with
      ideas on non-estrogen receptor associated actions of tamoxifen by way of
      alternate binding sites.

PMID- 8573713
TI  - Human mammary carcinomas express homologues of rat metastasis-associated variants
      of CD44.
AB  - Splice variants of CD44 expressed in a metastasizing cell line derived from a rat
      pancreatic adenocarcinoma have been shown recently to confer metastatic potential
      onto non-metastasizing rat pancreatic carcinoma and sarcoma cell lines.
      Homologues of these variants have also been detected in a variety of human
      malignancies. Using antibodies raised against a bacterially expressed fusion
      protein containing variant CD44 sequences, we have explored the expression of
      variant CD44 glycoproteins on tumors of the female breast. The material examined
      included normal tissue, hyperplastic lesions, 103 primary invasive mammary
      carcinomas, 10 in situ carcinomas, 12 local recurrences and 18 lymph node
      metastases. Using a polyclonal serum directed against several variant CD44
      epitopes, normal mammary epithelia as well as ductal hyperplasias were negative
      for these splice variants, while the variant CD44 epitopes were detectable in all
      but six of the primary invasive carcinomas. From the reaction with various
      monoclonal antibodies and polyclonal sera specific for individual epitopes it is
      obvious that the tumors predominantly express CD44 variants encoded by exons v5
      to v7. Interestingly, all investigated lymph node metastases reacted positively
      with the variant-specific antibodies, in contrast to primary tumors which reacted
      in 54% to 86% of the cases, depending on the antibody used. Statistical analysis
      revealed a significant correlation between expression of variant exons v3/v4 and
      v6 and increased tumor grade (p = 0.001 and p < 0.05, respectively; Fisher's
      exact test). Exon v6 is carried by the variants which confer metastatic
      capability in the rat. These results indicate that the expression of the CD44
      variants is upregulated in mammary carcinomas and is closely linked to tumor
      anaplasia.

PMID- 8573714
TI  - Breast cancer and importance of zygosity determination in triplet sisters.
AB  - This study is the first to examine the genetic risk in a breast cancer-prone
      family wherein two of three triplet sisters and their mother manifested breast
      cancer. The unaffected triplet, the proband, was found to be monozygotic with her
      deceased sister through DNA testing of tumor blocks and dizygotic to her living
      affected sister. Genetic counseling implications are discussed.

PMID- 8573715
TI  - Expression of Cdx-2 in the mouse embryo and placenta: possible role in patterning
      of the extra-embryonic membranes.
AB  - Three mouse homologues of the Drosophila homeotic gene Caudal (Cad) have been
      described. They are currently designated Cdx-1, Cdx-2, and Cdx-4. Cdx-1 and 2 are
      both strongly expressed in the adult mid- and hindgut, while Cdx-1 and 4 have
      been shown to be activated in the embryonic primitive streak. Using a polyclonal
      antibody against a fusion protein containing the amino terminal 109 amino acids
      of murine Cdx-2, we here describe the topographical location of the gene product
      from early cleavage to 12.5 days of embryonic development. Cdx-2 expression
      begins at 3.5 days and is confined to the trophectoderm, being absent from the
      inner cell mass. Subsequently, staining is located in the extra-embryonic
      ectoderm adjacent to the epiblast, but sparing the more superficially placed
      polar, as well as the mural trophoblastic cells. Continuing expression in the
      fetal membranes involves the chorion, the allantoic bud, and, at even later
      stages, the spongiotrophoblast. From 8.5 days, Cdx-2 begins to be expressed in
      embryonic tissues, principally (unlike Cdx-1) in the posterior part of the gut
      from its earliest formation, as well as in the tail bud and in the caudal part of
      the neural tube. Cdx-2 is, therefore, transcribed well before any other membrane
      of the Cad homologue group and of the related Hox-C group; its expression in the
      extra-embryonic membranes and in the hindgut reflects the phylogenetic
      relationship between the cloaca and the chorio-allantois and suggests the
      possibility that homeobox genes may be involved in placental development and/or
      patterning.

PMID- 8573716
TI  - Coordinate expression of vascular endothelial growth factor receptor-1 (flt-1)
      and its ligand suggests a paracrine regulation of murine vascular development.
AB  - Vascular endothelial growth factor (VEGF) is a candidate regulator of blood
      vessel growth during embryonic development and in tumors. To evaluate the role of
      VEGF receptor-1/flt-1 (VEGFR1/flt-1) in the development of the vascular system,
      we have characterized the murine homolog of the human flt-1 gene and have
      analyzed its expression pattern during mouse embryogenesis. Receptor binding
      studies using transfected COS cells revealed that the murine flt-1 gene encodes a
      high affinity receptor for VEGF. The apparent Kd for VEGF binding, as determined
      by Scatchard analysis, was 114 pM, demonstrating that VEGFR1/flt-1 has a higher
      affinity to VEGF than VEGF receptor-2/flk-1 (VEGFR2/flk-1). By in situ
      hybridization, VEGFR1/flt-1 was detected in the yolk sac mesoderm already at the
      early stages of vascular development, while the receptor ligand was expressed in
      the entire endoderm of 7.5-day mouse embryos. A comparison with VEGFR2/flk-1
      showed that the two receptors shared a common expression domain in the yolk sac
      mesoderm, but were expressed at different sites in the ectoplacental cone. The
      differential expression of the two VEGF receptors persisted in the developing
      placenta, where VEGFR1/flt-1 mRNA was detected in the spongiotrophoblast layer,
      whereas VEGFR2/flk-1 transcripts were present in the labyrinthine layer which is
      the site of VEGF expression. In the embryo proper, VEGFR1/flt-1 mRNA was
      specifically localized in blood vessels and capillaries of the developing organs,
      closely resembling the pattern of VEGFR2/flk-1 transcript distribution. In the
      developing brain, the expression of VEGF receptors in the perineural capillary
      plexus and in capillary sprouts which have invaded the neuro-ectoderm correlated
      with endothelial cell proliferation and brain angiogenesis. The data are
      consistent with the hypothesis that VEGF and its receptors have an important
      function both in the differentiation of the endothelial lineage and in the
      neovascularization of developing organs, and act in a paracrine fashion.

PMID- 8573717
TI  - Expression patterns of laminin receptor splice variants alpha 6A beta 1 and alpha
      6B beta 1 suggest different roles in mouse development.
AB  - The alpha 6 beta 1 integrin is a receptor for laminins and is present from early
      stages of mouse embryogenesis. In the present study we determined the temporal
      and spatial expression of the two cytoplasmic splice variants of the alpha 6
      integrin subunit, alpha 6A and alpha 6B, in the early- and mid-gestation mouse
      postimplantation embryo using RT-PCR, in situ hybridization, and
      immunofluorescence. Our results show that alpha 6B is present in the embryo at
      all stages studied and is expressed before alpha 6A. alpha 6A expression begins
      in 8.5 day p.c. embryos and is initially exclusively localized to the developing
      heart. In 8.5 (and 9.5) day p.c. embryos alpha 6A mRNA and protein are present in
      a gradient in the myocardium of the heart tube from strongest expression in the
      sinus venosus and in the common atrial chamber to a weakening expression along
      the ventricle and bulbus cordis. In 10.5 day p.c. embryos this gradient is less
      evident and in 12.5 day p.c. embryos alpha 6A mRNA and protein are present in
      comparable amounts between atria and ventricles. Neither alpha 6A nor alpha 6B is
      present in endocardial cushion tissue. By day 12.5 p.c. alpha 6A expression is
      also present in the developing epidermis, dental primordia, lens, gonads, and in
      a few epithelia such as those of the digestive tract. alpha 6B expression is
      always much more widespread than alpha 6A expression. For example, only alpha 6B
      is present in the myotome of the somites of 9.5 day p.c. embryos, in the
      developing central and peripheral nervous systems, and in the nephrogenic system
      at all stages studied, except after the differentiation of the gonads when alpha
      6A is also present. Furthermore, alpha 6B is the only splice variant present on
      endothelial cells. We also examined the distribution of the beta 4 integrin
      subunit to determine whether the alpha 6 beta 4 integrin was present during these
      stages of development. Beta 4 protein was absent in early postimplantation stages
      but was present in the epidermis and digestive tract of 12.5 day p.c. embryos.
      These results show a differential distribution of alpha 6A and alpha 6B during
      mouse development and thus strongly suggest a different function of these splice
      variants during embryogenesis. Our results point to a possible role for the alpha
      6A beta 1 integrin in the development of the myocardium of the developing heart,
      but not in the migration of endocardial cushion cells, while alpha 6B beta 1
      could be important in the developing nephrogenic and nervous systems.

PMID- 8573718
TI  - Relationship between fibronectin expression during gastrulation and heart
      formation in the rat embryo.
AB  - By utilizing myosin immunostaining, we were able to identify early rat myocardium
      as a thin epithelial sheet and realized that its cohesive movement toward the
      midline leads to the straight heart tube formation. Localization study of
      fibronectin mRNA and protein was, therefore, carried out to investigate its
      tissue origin and possible roles in facilitating mesoderm migration and heart
      formation. Fibronectin mRNAs were first detected throughout the mesoderm during
      the early primitive streak stage, suggesting that the mesoderm is the source of
      fibronectin. By pre-head fold (pre-somite) and head fold (early somite) stages,
      the mesoderm became largely down-regulated for fibronectin mRNAs, while it was
      also at these stages when myosin-positive myocardium formed itself into the
      epithelium and was subsequently folding toward the midline. Thus, there appears
      to be little fibronectin synthesis during and directly relevant to early heart
      tube formation. Later, during the early straight heart tube stage (5 somite and
      older), endocardium became highly positive for fibronectin mRNAs, suggesting that
      the endocardium is the major source of fibronectin for the cardiac jelly. Based
      on the results, we present a map for the early mammalian heart in which the heart
      is a single crescentic band lying in front of the prechordal plate. We also
      suggest a process for heart tube formation based on the cohesive movement of the
      myocardial epithelium. During heart tube formation, fibronectin protein had been
      deposited previously by the mesoderm and was found uniformly in the ECM and not
      newly produced by any adjacent tissue. The data contradict the endodermal
      guidance of heart migration by fibronectin gradient and suggest, instead, a
      permissive role for the fibronectin substrate.

PMID- 8573719
TI  - Molecular analysis of smooth muscle development in the mouse.
AB  - Little is currently known regarding the ontogeny of smooth muscle tissues during
      normal mammalian development. The alpha-smooth muscle and gamma-smooth muscle
      isoactins have been shown to be excellent molecular markers of smooth muscle cell
      phenotype. This study characterizes both the temporal and spatial patterns of
      alpha-smooth muscle and gamma-smooth muscle isoactin expression in the developing
      mouse. In situ analysis was performed on serial sections of whole mouse embryos
      on embryonic day 9, 11, 13, 15, and 17 using alpha-smooth muscle and gamma-smooth
      muscle isoactin-specific riboprobes. Distinct temporal and spatial patterns of
      alpha-smooth muscle and gamma-smooth muscle isoactin gene expression were
      observed in the developing gastrointestinal tract, urogenital tract, respiratory
      tract, and vascular system. Independent expression of the alpha-smooth muscle
      isoactin was observed during the early stages of skeletal, cardiac, and smooth
      muscle myogenesis as well as in a novel subset of distinct organs including the
      postnatal component of the hindgut, allantois, and primitive placenta. The
      results of this study indicate that distinct cellular phenotypes are involved in
      smooth muscle myogenesis and suggest that organ-specific mechanisms might exist
      for the initiation of smooth muscle development in vivo. In addition, the pattern
      of independent alpha-smooth muscle isoactin expression observed in this study
      provides novel information regarding the early stages of hindgut and placental
      development, and suggests that a common functional phenotype may be associated
      with the early stages of skeletal, cardiac, and smooth muscle myogenesis.

PMID- 8573720
TI  - Enhanced expression of mouse c-ski accompanies terminal skeletal muscle
      differentiation in vivo and in vitro.
AB  - Overexpression of either v-ski, or the proto-oncogene, c-ski, in quail embryo
      fibroblasts induces the expression of myoD and myogenin, converting the cells to
      myoblasts capable of differentiating into skeletal myotubes. In transgenic mice,
      overexpression of ski also influences muscle development, but in this case it
      effects fully formed muscle, causing hypertrophy of fast skeletal muscle fibers.
      In attempts to determine whether endogenous mouse c-ski plays a role in either
      early muscle cell determination or late muscle cell differentiation, we analyzed
      mRNA expression during muscle development in mouse embryos and during in vitro
      terminal differentiation of skeletal myoblasts. To generate probes for these
      studies we cloned coding and 3' non-coding regions of mouse c-ski. In situ
      hybridization revealed low c-ski expression in somites, and only detected
      elevated levels of mRNA in skeletal muscle beginning at about 12.5 days of
      gestation. Northern analysis revealed a two-fold increase in c-ski mRNA during
      terminal differentiation of skeletal muscle cell lines in vitro. Our results
      suggest that c-ski plays a role in terminal differentiation of skeletal muscle
      cells not in the determination of cells to the myogenic lineage.

PMID- 8573721
TI  - Cell and matrix specialisations of rhombomere boundaries.
AB  - Hindbrain segments, rhombomeres, define distinct cellular and molecular domains
      which furnish the ground plan for important aspects of neural and cranial
      development. In this study, further evidence is presented that the interfaces
      between rhombomeres, rhombomere boundaries, contain both cells and extracellular
      matrix with specialised characteristics. Cells at rhombomere boundaries show
      temporally and spatially distinct expression patterns of developmentally
      important genes. Towards the end of the developmental period when rhombomeres are
      present, a fan-shaped array of cells at rhombomere boundaries, that constitute
      the ventricular ridge, shows decreased expression of two genes (Hoxb-1 and Krox
      20), which earlier in development were expressed in all cells of specific
      rhombomeres. In contrast, these boundary cells show increased expression of
      another gene, Pax-6, which earlier in development has a rhombomere-specific
      expression pattern. A specialised identity for boundary cells is further
      suggested by increased labelling with an anti-vimentin antibody at rhombomere
      boundaries, indicating that at least some boundary cells are radial glia or glial
      precursors. In addition to distinct cellular properties, the extracellular domain
      at rhombomere boundaries is also specialised. Chondroitin sulphate proteoglycan
      (CSPG) immunoreactivity is increased and, as revealed by immuno-electron
      microscopy, localised to extracellular spaces. CSPG is also enriched in
      boundaries regenerated after ablation, or boundaries generated ectopically by
      rhombomere transplantation. We propose that rhombomere boundaries form their
      characteristic morphology at the interface between groups of cells with differing
      molecular characteristics, representing different cell states. A specialised band
      of cells then develops at the interface. Both the boundary cells and extracellur
      matrix have characteristics which could be important in later events of neural
      development such as axon guidance and cell migration.

PMID- 8573722
TI  - Expression of M-twist during postimplantation development of the mouse.
AB  - The murine homologue of the Drosophila twist gene has been shown to be essential
      for head mesenchyme formation and to act as an inhibitor of muscle
      differentiation. This paper presents a detailed analysis of M-twist expression
      patterns from day 7 post coitum (p.c.) to day 18 p.c., indicating a more general
      function of the M-twist gene. At day 7 p.c., M-twist is expressed in the mesoderm
      outside the primitive streak. Later M-twist message is predominantly found in the
      somites, the head mesenchyme, the branchial arches, the limbs, and in the
      mesenchyme underneath the epidermis. Beginning at day 8 p.c., M-twist is mainly
      expressed in undifferentiated cells committed to muscle and cartilage
      development: this expression is consistent with a suggested role of M-twist in
      inhibiting overt muscle and cartilage differentiation. However, during
      organogenesis, M-twist is expressed in several areas of mesenchyme-epithelia
      interactions, suggesting additional tissue specific functions.

PMID- 8573723
TI  - Cooperative model of epithelial shaping and bending during avian neurulation:
      autonomous movements of the neural plate, autonomous movements of the epidermis,
      and interactions in the neural plate/epidermis transition zone.
AB  - Morphogenetic movements during neurulation cause a tissue to change shape within
      the plane of the epithelium (e.g., conversion of the oval neural plate into the
      narrow spinal plate and the wide brain plate), cause bending out of the plane of
      the epithelium (e.g., raise the neural folds and curl the neural plate into a
      tube), or contribute to both phenomena. In this study, pieces that contain neural
      plate alone, epidermis alone, or both tissues (with or without underlying
      tissues) are cut from chick embryos and allowed to develop for up to 24 hr.
      Examination of histological sections through such isolates allows analysis of the
      formation of neural folds. When the neural plate/epidermis transition zone is
      disrupted, neural folds do not form. Conversely, when the transition zone remains
      intact, neural folds form. Neural folds form even when most of the medial neural
      plate and lateral epidermis has been removed, leaving only the isolated
      transition zone. These data indicate that the transition zone is both necessary
      and sufficient for the formation of neural folds. The transition zone may play a
      number of roles in epithelial bending including organizing, focussing, and
      redirecting movements that are autonomous to the neural plate or epidermis. Time
      lapse video recording, and sequential photographs allowed the documentation of
      such movements. Neural plate isolates exhibit autonomous rostrocaudal lengthening
      and mediolateral narrowing. Isolated strips of epidermis exhibit autonomous
      movements which, unlike wound-healing movements, are unidirectional (medial), and
      region-specific (beginning and reaching their greatest extent in the cranial
      region). Isolated pieces of neural plate or epidermis remain flat instead of
      bending, providing further evidence that the transition zone is necessary for the
      formation of neural folds.

PMID- 8573724
TI  - Protein characterization and targeted disruption of Grg, a mouse gene related to
      the groucho transcript of the Drosophila Enhancer of split complex.
AB  - The Grg gene encodes a 197 amino acid protein homologous to the amino-terminal
      domain of the product of the groucho gene of the Drosophila Enhancer of split
      complex. Analysis with a polyclonal antisera specific for the Grg protein
      revealed that Grg is a 25 kd nuclear protein that can participate in specific
      protein-protein interactions. A null mutation of the Grg gene was constructed by
      gene targeting. Mice homozygous for this mutation completed embryogenesis and
      were born, but exhibited varying degrees of post-natal growth deficiency. No
      dosage-sensitive genetic interaction was detected between the Notch1 and Grg
      genes in mice heterozygous for a Notch1 mutant allele and homozygous for the Grg
      null mutation.

PMID- 8573725
TI  - Proceedings of the 4th International Symposium on Hypertension Associated with
      Diabetes Mellitus. A satellite symposium of the 15th International Diabetes
      Federation Congress. Otsu, Japan, November 4-5, 1994.

PMID- 8573726
TI  - Regulation of blood pressure by nitroxidergic nerve.
AB  - We discovered vasodilator innervation first in canine cerebral arteries, in which
      nitric oxide (NO) acts as a neurotransmitter; thus, the nerve is called
      nitroxidergic. Then, reciprocal innervation of noradrenergic and nitroxidergic
      nerves in canine peripheral arteries was determined; adrenergic nerve-mediated
      vasoconstriction is predominant over vasodilatation mediated by NO derived from
      the nerve. In anesthetized dogs, hypertension induced by NO synthase inhibitors
      is suppressed by hexamethonium. It is hypothesized that impairment of
      nitroxidergic nerve function by NO synthase inhibition is mainly involved in the
      genesis of hypertension.

PMID- 8573727
TI  - Endothelium-dependent relaxation in peripheral vasculature and kidney of non
      insulin-dependent diabetes mellitus.
AB  - Desmopressin (DDAVP), an AVP.V2-receptor agonist, evokes endothelium-dependent
      relaxation (EDR) due to nitric oxide (NO), EDR factor (EDRF) in the systemic
      vasculature, and glomerular afferent arterioles via AVP receptor(s). Glyceryl
      trinitrate (GTN) causes endothelium-independent (nonreceptor-mediated)
      vasodilation. We elucidated the possible involvement of EDRF in early non-insulin
      dependent diabetes mellitus (NIDDM) and glomerular hyperfiltration (GHF) by DDAVP
      and GTN infusions. Patients with advanced DM nephropathy (DM.Np) (n = 7) were
      also examined. DDAVP and GTN decreased the mean blood pressure in DM with GHF (DM
      + GHF) and without GHF (DM-GHF) greater than that in normal subjects (N), without
      any difference in the heart rate changes in any group. Plasma levels of cGMP, a
      cellular messenger of NO, were significantly increased by DDAVP and GTN with a
      similar increment in each group. DDAVP caused a significant increase in urinary
      cGMP excretion in each group with a similar increment in each group. However, it
      caused a transient increase in creatinine clearance only in DM + GHF although GTN
      did not, and an exaggerated excretion of urinary albumin in early NIDDM,
      especially in DM+GHF, without a change in beta 2-microglobulin excretion. In
      contrast, in DM.Np GTN caused a decrease in blood pressure and an increase in
      plasma cGMP levels, but DDAVP did not. In conclusion, in peripheral vasculature
      and kidney, an enhanced sensitivity of vascular smooth muscle to NO is present in
      early NIDDM. The exaggerated dilation of glomerular afferent arterioles by
      preferentially produced NO in in situ, which causes a rise in PGC, might be
      partly responsible for the glomerular hyperfiltration and subsequently the
      increase in the glomerular protein permeation of DM+GHF. However, in peripheral
      blood vessels of DM.Np EDR is impaired. Thus, EDR seems to change with the
      development of NIDDM.

PMID- 8573728
TI  - Integrated analysis of erythrocyte Na+/H+ antiport activity and left ventricular
      myocardial function in type I insulin-dependent diabetes mellitus.
AB  - Membrane NA+/H+ exchanger regulates cell pH, volume, and growth. Abnormal
      activities have been reported in essential hypertension and type I insulin
      dependent diabetes mellitus (IDDM). The aim of this study was to analyze the
      relationship between erythrocyte NA+/H+ antiport activity and myocardial
      anatomical and functional parameters in normotensive type I insulin-dependent
      diabetic patients. We evaluated 26 insulin-dependent diabetic patients (20 normo-
      and 6 microalbuminuric) and 17 age- and sex-matched healthy controls. Plasma and
      urine analytes as well as erythrocyte NA+/H+ antiport rate were measured. M-Mode-
      and 2D echocardiograms with Doppler analysis were performed in all subjects.
      Diabetic people, both normo- and microalbuminuric, had a Na+/H+ antiport activity
      significantly higher than control subjects (p < 0.01). All echocardiographic
      parameters relative to left ventricular volume, cardiac mass and systolic
      function overlapped in the study groups. Of Doppler indexes, evaluating the left
      ventricular diastolic filling, the late peak flow velocity (peak A) was
      significantly higher in diabetic patients (p < 0.01). E/A ratio was heightened in
      the control group compared to diabetics, as a whole as well separately considered
      (p < 0.01). Antiport significantly correlated with PWTh, STh, E/A, UAER, serum
      sodium, and gender (p < 0.0001). The linear and significant correlation found
      between Na+/H+ exchange and some cardiac indexes suggest the increased Na+/H+
      antiport activity as possible predictive risk factor for the development of
      diabetic cardiomyopathy.

PMID- 8573729
TI  - Prediabetic blood pressure and familial predisposition to renal disease in Pima
      Indians with non-insulin-dependent diabetes mellitus.
AB  - Renal disease is a frequent complication of non-insulin-dependent diabetes in the
      Pima Indians from the Gila River Indian Community in Arizona. This review
      describes the relationship between prediabetic blood pressure and the subsequent
      development of renal disease, and characterizes the familial aggregation of
      diabetic renal disease in this population.

PMID- 8573730
TI  - Effects of a calcium channel blocker, manidipine, on insulin sensitivity in
      essential hypertensives.
AB  - This study was designed to investigate the effects of the calcium channel blocker
      manidipine on insulin-dependent glucose uptake (insulin sensitivity) and insulin
      action to renal sodium handling and pressor systems in essential hypertensive
      (EHT). Seven EHT were hospitalized and a 2-h euglycemic hyperinsulinemic glucose
      clamp was performed in a fasting condition before and after 2 weeks
      administration of manidipine (20 mg/day). Insulin sensitivity was evaluated as M
      value calculated from the infusion rate of glucose. Manidipine administration
      decreased mean blood pressure and increased M-value significantly in EHT. Before
      the manidipine treatment, hyperinsulinemia during the clamp induced a decrease of
      urinary sodium excretion and increases of plasma norepinephrine and plasma renin
      activity in EHT. After manidipine treatment, however, hyperinsulinemia induced
      natriuresis and did not augment the pressor systems activity. Thus, the calcium
      channel blocker improved insulin resistance as assessed by glucose clamp
      technique in EHT. Suppression of augmented renal sodium reabsorption and pressor
      system activities of insulin may be connected with the hypotensive mechanisms and
      the natriuresis caused by calcium channel blockers.

PMID- 8573731
TI  - Effects of high-calorie diet on blood pressure and sodium retention in
      spontaneously hypertensive rats and normotensive Wistar-Kyoto rats.
AB  - Previous reports from our laboratory have documented that spontaneously
      hypertensive rats (SHR) have insulin resistance and that insulin resistance is
      enhanced by high-caloric diet (HCD) feeding. The aim of this study was to
      elucidate the effect of HCD on blood pressure and sodium retention in both SHR
      and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were divided into two
      groups. One group of rats was fed normal diet (ND). The other rats were fed HCD.
      After the 8-week feeding period, insulin suppression tests were performed. The
      animals were individually housed in metabolic cages for the last 2 days of the
      experiment. Food consumption was recorded for 24 h, and a 24-h urine was
      collected to calculate the sodium excretory ratio. In both strains, body weight
      was significantly increased by HCD feeding. Blood pressure was significantly
      elevated in SHR by HCD feeding, whereas that of WKY was not affected by HCD
      feeding. In both strains, steady-state plasma glucose (SSPG) during the insulin
      suppression test was higher in the HCD group than in the ND group. SSPG was
      consistently higher in SHR than in WKY treated with HCD. Urinary sodium excretion
      ratio was significantly decreased in SHR by HCD, and plasma potassium
      concentrations were significantly lower in SHR with HCD than in SHR with ND,
      whereas those of WKY were not affected by HCD feeding. SHR are more sensitive to
      the induction of insulin resistance than WKY, resulting in sodium retention and
      elevation of blood pressure.

PMID- 8573732
TI  - The characteristics of renal hemodynamics in diabetic spontaneously hypertensive
      rats in comparison with diabetic Wistar-Kyoto rats.
AB  - Diabetic Sprague-Dawley (SD) rats are known to exhibit renal hyperfiltration and
      hyperperfusion accompanied by renal hypertrophy. We examined whether such
      characteristics of renal hemodynamics in diabetic SD rats are also observed in
      diabetic spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. SHR
      and WKY rats were divided into four groups: D-S, diabetic SHR; N-S, nondiabetic
      SHR; D-W, diabetic WKY rats; and N-W, nondiabetic WKY rats. Streptozotocin (STZ),
      90 mg, was intraperitoneally injected to induce diabetes. Renal blood flow (RBF)
      and glomerular filtration rate (GFR) were measured by a clearance method with
      paraaminohypurate and insulin, respectively, 7-12 days after diabetes induction.
      In D-S and D-W, there was no increase in the kidney weight and RBF, in spite of
      significant increases in GFR and fasting blood sugar levels. These results
      indicate that, in both WKY and SHR, diabetes does not always produce renal
      hypertrophy and does not result in an increase in RBF.

PMID- 8573733
TI  - Hyperbetalipoproteinemia with small low-density lipoprotein, a characteristic
      disorder of lipoprotein in essential hypertension.
AB  - The purpose of the present study was to elucidate the characteristic lipoprotein
      disorder in essential hypertension. Twenty-six patients with essential
      hypertension (HT) but without diabetes mellitus or obesity and 24 healthy
      subjects (control) were recruited into this study. Lipoproteins of HT and
      controls were separated by ultracentrifugation to very-low-density lipoprotein
      (VLDL), intermediate density lipoprotein (IDL), low-density liproprotein (LDL),
      and (HDL) fractions. Cholesterol and triglycerides were determined with enzyme
      assay, and apoB were determined by highly sensitive latex agglutination (Kyowa
      hakko Co. LD). There was no difference in age (mean +/- SE; HT, 63 +/- 2 versus
      control, 60 +/- 2 years) or body-mass index (22.7 +/- 0.4 versus 21.7 +/- 0.5
      kg/m2) between HT and controls. Blood pressure in HT and controls was 158 +/-
      2/87 +/- 12 mm Hg and 123 +/- 3/72 +/- 2 mm Hg, respectively. Cholesterol did not
      change significantly in plasma (192.1 +/- 7.0 versus 176.4 +/- 4.2 mg/dL), VLDL
      (15.2 +/- 2.4 versus 11.8 +/- 1.7 mg/dL), IDL (14.8 +/- 2.4 versus 10.7 +/- 1.6
      mg/dL), LDL (93.7 +/- 4.6 versus 83.1 +/- 3.9 mg/dL), nor in HDL (51.9 +/- 2.7
      versus 58.1 +/- 3.2 mg/dL). Triglycerides (TG) increased in plasma (120.0 +/-
      10.0 versus 87.5 +/- 9.3 mg/dL, p < 0.05), although TG did not change in all
      subfractions. ApoB increased in plasma (105.5 +/- 5.1 versus 85.6 +/- 3.6 mg/dL,
      p < 0.01), IDL (9.0 +/- 1.3 versus 5.4 +/- 0.6 mg/dL, p < 0.05), and LDL (76.3 +/
      4.3 versus 59.4 +/- 3.7 mg/dL, p < 0.01) in HT compared with controls. The ratio
      of cholesterol to apoB in LDL decreased (1.27 +/- 0.06 versus 1.48 +/- 0.08, p <
      0.05). In essential HT, number of apoB containing lipoproteins (IDL, LDL)
      increased. Low ratio of cholesterol to apoB was noted in LDL, indicating the
      presence of small, dense LDL. As cholesterol in LDL was normal,
      hyperbetalipoproteinemia is also a characteristic disorder of essential HT.

PMID- 8573734
TI  - Insulin resistance in non-insulin-dependent diabetes mellitus is associated with
      microalbuminuria independently of ambulatory blood pressure.
AB  - Microalbuminuria in both insulin-dependent (IDDM) and non-insulin-dependent
      diabetes mellitus (NIDDM) is a marker for insulin resistance. Microalbuminuria is
      also associated with hypertension, itself an insulin-resistant state. Therefore,
      in order to examine the independent relationships of microalbuminuria with blood
      pressure and insulin resistance, we measured ambulatory blood pressure (Takeda TM
      2420), insulin resistance (modified Harano method), and urinary albumin excretion
      rate (overnight urine collection) in 36 subjects with NIDDM. Albumin excretion
      correlated with 24-h systolic blood pressure (r = 0.49, p = 0.003), and insulin
      sensitivity (r = -0.39, p = 0.007). Microalbuminuric subjects had reduced insulin
      sensitivity compared with normoalbuminuric subjects [Mean (SD) 2.95 (0.33) versus
      4.67 (0.56) ml.kg-1.min-1; p = 0.013]. In multivariate analysis including
      ambulatory blood pressure and insulin resistance, urinary albumin excretion was
      associated primarily with insulin resistance, with smaller contributions from
      glycated hemoglobin and male gender. These data suggest that microalbuminuria in
      NIDDM, although associated with hypertension, is also independently associated
      with insulin resistance.

PMID- 8573735
TI  - 24-h ambulatory blood pressure, daytime and nighttime urinary albumin and retinol
      binding protein excretion in type I diabetic patients.
AB  - We studied 24-h ambulatory blood pressure (SBP, DBP), actual glycemic control
      assessed from seven blood glucose measurements, 16-h daytime and 8-h nighttime
      urinary excretion of albumin (UAE) and retinol-binding protein (URBP) in 20
      normoalbuminuric (group A, nighttime UAE < 20 micrograms/min) and 20
      microalbuminuric and low-proteinuric type I diabetic patients (group B, nighttime
      UAE 20-500 micrograms/min) matched for age and diabetes duration. Glycemic
      control was similar in the two groups. Daytime and nighttime SBP and DBP were
      higher in group B compared to group A (p < 0.01). Nighttime decrease in SBP and
      DBP correlated with nighttime decrease in UAE in group B (p < 0.05, p < 0.001),
      but not in group A. There was no correlation between BP and actual glycemic
      control in either group. We found higher daytime and nighttime URBP in group B
      compared to group A (p < 0.05). We conclude that, in microalbuminuric and low
      proteinuric patients, daytime and nighttime BP was elevated but still in the
      normal or borderline range, and nighttime decrease in BP correlated with
      nighttime decrease in UAE but not with actual glycemic control. Increased URBP in
      these patients suggests slightly impaired proximal tubular function in early
      stages of diabetic nephropathy.

PMID- 8573736
TI  - 24-h blood pressure recordings in type I diabetic patients.
AB  - Ambulatory blood pressure (AMBP) is of particular interest in diabetes because of
      the close association between elevated BP and diabetic nephropathy and the
      attenuated night drop in some diabetic subgroups: (1) Normoalbuminuric patients:
      If standardized for type of day (work or day off), coefficient of variation (CV)
      for 24 h AMBP is 2%-3% and 5%-6% for night/day ratio. The male-female difference
      in AMBP seen in healthy subjects is reduced in diabetes. Smoking did not
      significantly affect AMBP. AMBP is increased in patents with high normal urinary
      albumin excretion (UAE). Night/day ratio of AMBP and night heart rate is higher
      in long than short term diabetic patients. This difference in night/day ratio is
      not significant if the slightly higher UAE in long-term patients is accounted
      for. (2) Microalbuminuric patients: Diastolic night/day ratio is increased
      compared with healthy controls, with the value for normoalbuminuric patients in
      between. A large overlap between groups is evident. Thus the prognostic value of
      a single abnormal night/day ratio is doubtful. If divided into dippers and
      nondippers, no difference in extracellular- or plasma volume is found, but
      nondippers have a lower plasma aldosterone and arginine vasopressin level,
      possibly to counteract volume expansion. (3) Patients with overt nephropathy: A
      marked increased in AMBP and a clear reduction of the nocturnal blood pressure
      fall is seen. In conclusion, AMBP (but not night/day ratio) is highly
      reproducible. The association between elevated AMBP, elevated night/day ratio,
      and pathological UAE is detectable even in normoalbuminuric patients. The
      prognostic importance of abnormal circadian variation of BP is unsettled.

PMID- 8573737
TI  - Protein kinase C in diabetic nephropathy.
AB  - Protein kinase C is activated in numerous tissues obtained from diabetic animals
      and in several cultured cell systems exposed to high media glucose in vitro
      including glomerular mesangial cells. Several activators of protein kinase C,
      such as high media glucose, angiotensin II, phorbol ester, low density
      lipoprotein, and the thromboxane analogue U-46619, increase TGF beta bioactivity
      or mRNA expression and increase the synthesis of extracellular matrix proteins by
      mesangial cells in culture. The studies described in the present report support
      the hypothesis that activation of protein kinase C by thromboxane, an eicosanoid
      whose production is known to be elevated in diabetes, increases TGF beta
      production by mesangial cells in culture. TGF beta then acts to increase
      extracellular matrix protein synthesis through a mechanism that does not require
      active protein kinase C. Thus, activation of protein kinase C in the glomerulus
      in diabetes could contribute to mesangial expansion by stimulating active TGF
      beta production.

PMID- 8573738
TI  - Abnormalities in protein kinase C and MAP kinase cascade in mesangial cells
      cultured under high glucose conditions.
AB  - In order to clarify the mechanism of mesangial cell dysfunction in diabetes, we
      examined the activities of protein kinase C (PKC) and mitogen-activated protein
      kinase (MAPK), important kinases in various cellular functions, and also
      evaluated the isoenzymes of PKC in mesangial cells cultured under high glucose
      conditions. Exposure of cells to high concentrations (27.8 mM) of glucose for 5
      days resulted in a significant elevation of PKC activities in the membrane
      fraction. MAPK was also activated in cells cultured under high glucose
      conditions. Of the PKC isoenzymes, the levels of PKC alpha and zeta were
      significantly increased in the membrane fraction after 5 days of exposure to high
      concentrations of glucose. These results indicate that the translocation of PKC
      alpha and zeta and the activation of MAPK under high glucose conditions might be
      underlying mechanisms of the functional disturbance of mesangial cells in
      diabetes.

PMID- 8573739
TI  - Cyclic nucleotides attenuate endothelin-1-induced activation of mitogen-activated
      protein kinase in cultured rat mesangial cells.
AB  - In order to clarify the mechanisms of interaction between endothelin-1 (ET-1) and
      cyclic AMP (cAMP) or cyclic GMP (cGMP), we examined the effects of cAMP or cGMP
      on ET-1-induced activation of mitogen-activated protein kinase (MAPK), one of the
      key enzymes in the signal transduction of ET-1, in cultured rat mesangial cells.
      ET-1 was able to activate both p42 and p44 MAP kinases in a dose-dependent
      manner. Cell permeable analogues of cAMP and cGMP, dibutylyl cAMP (BT2-cAMP) and
      8 bromo cGMP (8br-GMP), significantly inhibited ET-1-induced activation of MAPK.
      Atrial natriuretic peptide (ANP), which increased cellular cGMP, was able to
      inhibit ET-1-induced activation of MAPK in a dose-dependent manner, while c-ANP,
      an analogue specific to the clearance receptors of ANP, exerted no effect. These
      results indicate that cAMP and cGMP could modulate the action of ET-1 in
      mesangial cells at a step of the activation of MAPK.

PMID- 8573740
TI  - Extracellular matrix and its interactions in the diabetic kidney: a molecular
      biological approach.
AB  - Increased extracellular matrix (ECM) is the ultrastructural hallmark of diabetic
      microangiopathy. Its accumulation within the kidney is directly linked to the
      clinical manifestations of diabetic nephropathy, namely proteinuria and declining
      renal function. The pathogenesis of ECM changes in diabetes is not well
      understood, but is likely to involve interaction between cells, growth factors,
      structural proteins, and cell receptors for these molecules. Molecular biological
      techniques may offer the necessary tools for gaining insight into the
      pathogenetic processes that eventually lead to renal failure in diabetes.

PMID- 8573742
TI  - Upregulation of insulin-like growth factor receptor gene in experimental diabetic
      rat glomeruli.
AB  - Renal hypertrophy is a characteristic and early manifestation of diabetes in
      human and experimental animals. We examined the precise distribution of insulin
      like growth factor-I (IGF-I) receptor mRNA in the experimental diabetic rat
      kidney using a nonradioactive in situ hybridization technique. Expression of IGF
      I receptor mRNA was rarely seen in the glomeruli of control rats. IGF-I receptor
      mRNA was detected after induction of diabetes in glomerular mesangial, visceral
      epithelial, and parietal epithelial cells. The number of IGF-I receptor mRNA
      positive cells in a glomerulus increased significantly at 4 weeks as compared
      with the control rats. Overexpression of IGF-I receptor in glomerular cells may
      contribute to the glomerular hypertrophy in diabetic nephropathy.

PMID- 8573741
TI  - Role of protein kinase C and cyclic AMP/protein kinase A in high glucose
      stimulated transcriptional activation of collagen alpha 1 (IV) in glomerular
      mesangial cells.
AB  - The elevated mRNA levels encoding matrix components in glomeruli isolated from
      streptozotocin-induced diabetic rats provide evidence that stimulation of matrix
      synthesis is important in early phases of diabetic glomerulopathy. We and others
      have demonstrated that high glucose stimulates collagen mRNA levels in short-term
      mesangial cell culture. To test whether transcriptional activation is operative
      and to gain insights into the underlying mechanisms, we studied a murine
      mesangial cell line stably transfected with a minigene expressing luciferase
      driven by 5'-flanking and first-intron regions of the alpha 1(IV) gene. High
      glucose stimulated luciferase activity dose and time dependently, with optimal
      stimulation (two-fold) achieved after 48 h in 450 mg/dL glucose (G450) versus 100
      mg/dL (G100). We next tested the involvement of protein kinase C (PKC) because
      high glucose has been shown to stimulate de novo synthesis of diacylglycerol
      (DAG). Increasing PKC activity by treatment with a DAG analogue or active phorbol
      ester stimulated luciferase activity preferentially in G100; addition of the PKC
      inhibitors staurosporine or calphostin C markedly inhibited luciferase activity
      preferentially in G450. Thus high glucose promotes transcriptional activity of
      alpha 1(IV) gene through PKC activation. We also tested the involvement of
      protein kinase A (PKA). Intracellular cyclic AMP levels were increased two fold
      after 48 h in G450 versus G100, and addition of 8-Br-cAMP (0.1 mM) preferentially
      stimulated luciferase activity by almost three fold in G100 versus only 1.2-fold
      in G450. Hence, the signal-transduction mechanisms underlying the transcriptional
      activation of alpha 1(IV) gene in mesangial cells by high glucose are mediated by
      pathways involving the PKC system and possibly the cAMP/PKA system.

PMID- 8573743
TI  - Advanced glycation endproducts and diabetic nephropathy.
AB  - Diabetic nephropathy is currently the single largest cause of endstage renal
      disease (ESRD) in the United States and many European countries. The primary
      cause for the development of diabetic complications (including diabetic
      nephropathy) is persistent exposure to hyperglycemia, although genetic and other
      incompletely understood factors also play an important role. Although much
      consideration has been given to the pathogenesis and genetics of the disease
      itself, the mechanisms by which persistent exposure to hyperglycemia cause
      biochemical and metabolic alterations have been very sketchily understood.
      Recently, a growing body of evidence has linked the accumulation of the late
      products of glucose-protein interaction to a variety of chronic complications,
      including diabetic nephropathy. The formation of irreversible advanced
      glycosylation endproducts (AGEs) resulting from the spontaneous reaction between
      glucose and proteins occur most noticeably on long-lived structural proteins.
      Recent studies demonstrate that the pathogenesis of diabetic nephropathy is
      caused by the hyperglycemia-accelerated formation of AGEs. Also, reactive AGE
      peptides in the circulation are thought to play a role as a new version of so
      called middle molecule toxic substances. This evidence is opening a new window
      for our understanding of the pathogenesis of diabetic nephropathy.

PMID- 8573744
TI  - Localization of advanced glycation endproducts in the kidney of experimental
      diabetic rats.
AB  - Advanced glycation endproducts (AGE) have been proposed as a major mediator in
      the development of various diabetic complications. In order to evaluate the
      involvement of AGE in the development of diabetic nephropathy, we examined the
      localization of AGE in the kidney of the streptozotocin-induced diabetic rats
      immunohistochemically using a monoclonal antibody directed to AGE. In the
      diabetic rats, glomerular hypertrophy, thickening of the glomerular basement
      membrane, and expansion of mesangial matrix were observed. AGE was detected in
      expanded mesangial area and glomerular basement membrane in the kidneys of
      diabetic rats. The present results suggest that AGE may participate in the
      development of diabetic nephropathy.

PMID- 8573745
TI  - Angiotensin-converting enzyme (ACE) gene polymorphism in type II diabetic
      patients with increased albumin excretion rate.
AB  - Approximately one in three patients with diabetes is at risk of developing kidney
      disease, despite current methods of treatment. It has long been suspected that
      diabetic kidney disease has a genetic basis, but this has been difficult to
      prove. Polymorphisms of the angiotensin-converting enzyme (ACE) gene have been
      shown to be related to the occurrence of nephropathy in type I diabetic patients.
      This study showed that there was no association in the ACE genotype frequency and
      increased albumin excretion rate in type II diabetic patients.

PMID- 8573746
TI  - Genetic susceptibility to diabetic kidney disease: an update.
AB  - Various types of evidence supporting the hypothesis of genetic susceptibility to
      diabetic kidney disease (DKD) are reviewed. Three groups of studies were
      distinguished: (1) epidemiologic and family studies, (2) studies of phenotypic
      markers/predictors, and (3) studies of DNA markers. Although all of these studies
      point to the existence of susceptibility to DKD, further research is required.
      Particularly needed are studies that examine the mechanisms of interaction
      between genetic susceptibility to DKD and poor glycemic control, and studies to
      identify specific molecular mechanisms underlying this susceptibility.

PMID- 8573747
TI  - Phenotypic changes of the mesangium in diabetic nephropathy.
AB  - In diabetic nephropathy there is accumulation of matrix proteins. Overproduction
      of these matrix proteins considered to be due to the phenotypic change of
      mesangial cell. In order to detect the phenotypic change of the mesangial cell,
      renal biopsy specimens from patients with diabetic nephropathy were stained with
      antibodies against various types of collagens and contractile-associated protein,
      caldesmon. Type III collagen was not stained in the glomerulus and type VI
      collagen showed mesangial pattern from normal controls. In diabetes, mesangial
      staining of type III collagen and increases in type VI collagen were observed in
      the mesangium. Increased mesangial staining of caldesmon was noted in the
      glomerulus from diabetic nephropathy in contrast to only vessel staining from
      normal controls. These results indicate that phenotypic changes are noted in the
      mesangium in diabetes. Expression of contractile-associated protein such as
      caldesmon, would serve as a useful marker to predict glomerulosclerosis.

PMID- 8573748
TI  - The ultrastructural disruption of the glomerular basement membrane in diabetic
      nephropathy revealed by "tissue negative staining method".
AB  - To clarify the ultrastructural changes of the glomerular basement membrane (GBM)
      in diabetic nephropathy, the renal tissues of the patients with diabetic
      nephropathy were examined by electron microscopy using our newly devised "tissue
      negative staining method." A fine meshwork structure consisting of fibrils
      forming the small pores are observed in the normal human GBM. The diameter of
      these pores was slightly smaller than that of human albumin molecules. The GBM in
      patients with diabetic nephropathy showed irregular thickening. At higher
      magnification, cavities and tunnel structures, which were not seen in normal
      controls, were observed in the thickened GBM. As the diameters of the cavities
      and tunnels were far larger than the dimensions of albumin molecules, these
      enlarged structures are considered to allow serum protein molecules to pass
      through the GBM from the capillary lumen to the urinary space. The present
      results suggest that the cause of massive proteinuria in diabetic nephropathy is
      the disruption of the size barrier of the GBM.

PMID- 8573749
TI  - Ultrastructural study of glomerular basement membrane in diabetic rats by the
      quick-freezing and deep-etching method.
AB  - The three-dimensional ultrastructure of glomerular basement membrane (GBM) and
      mesangium in very early stage of streptozotocin-induced diabetic rat kidney was
      examined by the quick-freezing and deep-etching method. In control rats GBM was
      composed of three layers. Outer and inner layers consisted of files of fibrils
      that connected endothelial or epithelial cells perpendicularly with meshwork of a
      middle layer that also consisted of dense meshwork structure composed of fibrils.
      In diabetic rats, perpendicular fibrils of the inner layer were irregular and
      disrupted, and the layer was enlarged. The meshwork structure of the middle layer
      was irregularly enlarged, and matrix fibrils were disrupted. Early insulin
      treatment prevents these morphological changes. Furthermore, early administration
      of beraprost sodium, a PGI2 analogue, might have beneficial effects in preventing
      the progression of these changes.

PMID- 8573750
TI  - The effect of macrophage colony-stimulating factor (M-CSF) on the progression of
      lipid-induced nephrotoxicity in diabetic nephropathy.
AB  - In order to elucidate the role of macrophage in lipid-induced nephrotoxicity in
      diabetic nephropathy, we examined the effect of macrophage colony-stimulating
      factor (M-CSF) on the progression of renal lesions in hypercholesterolemic
      steptozotocin (STZ)-diabetic rats fed with high cholesterol chow.
      Hypercholesterolemia aggravated albuminuria in diabetic rats accompanied by
      infiltration of macrophages in glomeruli. Treatment with M-CSF suppressed
      simultaneously infiltration of glomerular macrophages and urinary albumin
      excretion in hypercholesterolemic diabetic rats. These results suggest that
      infiltration of glomerular macrophage has a primary role in lipid-induced
      nephrotoxicity in diabetic nephropathy, and M-CSF is involved in this process as
      a preventive factor.

PMID- 8573751
TI  - Vascular changes in the diabetic kidney: effects of ACE inhibition.
AB  - The effects of angiotensin-converting enzyme (ACE) inhibition with perindopril on
      renal vascular structure were studied in control and streptozotocin diabetic male
      Sprague-Dawley rats after 3 weeks. After kidneys were perfusion-fixed at systolic
      blood pressure, morphometric analysis of vascular structural changes in the media
      of the renal vasculature at the cortico-medullary junction was performed.
      Vascular hypertrophy was present in the diabetic vessels, as assessed by an
      increase in medial cross-sectional area for a given lumen size. This relative
      increase in medial area was prevented by perindopril treatment, consistent with
      an antitrophic effect on diabetic kidney vessels by ACE inhibition. The diabetic
      kidney had an increased proportion of small vessels less than 50 microns diameter
      at the cortico-medullary junction, perhaps representing diabetes induced
      angiogenesis. This subpopulation of vessels was reduced in number after
      perindopril treatment. Our data support a role for increased activity of
      angiotensin converting enzyme as a mechanism for vascular hypertrophy, which may
      be involved in the pathogenesis of diabetic vasculopathy and nephropathy.

PMID- 8573752
TI  - Acute effect of calcium blocker on renal hemodynamics in diabetic spontaneously
      hypertensive rat.
AB  - This study was done to examine the acute effect of a calcium channel blocker on
      renal hemodynamics in the diabetic spontaneously hypertensive rat (SHR).
      Streptozotocin was used to induce diabetes, and barnidipine (B) was used as a
      calcium blocker. Renal blood flow (RBF) and glomerular filtration rate (GFR) were
      measured by a clearance method with paraaminohypurate (PAH) and inulin,
      respectively. Rats were divided into two groups: nondiabetic SHR, N-SHR; diabetic
      SHR, DM-SHR. B increased RBF in N-SHR (7.44 +/- 1.99 versus 8.50 +/- 1.97
      mL/min/g.kw) while there was no change in DM-SHR. B reduced renovascular
      resistance (RVR) in DM-SHR and N-SHR. B increased GFR in N-SHR (1.15 +/- 0.24
      versus 1.34 +/- 0.25 mL/min/g.kw), in spite of no changes in DM-SHR. B did not
      modify filtration fraction (FF) in both groups. These results indicate (1) in
      SHR, B exerts beneficial effects on hypertensive renal damage by reducing mean
      arterial pressure (MAP), RVR, RBF, and GFR; (2) in diabetic SHR, B is less
      effective in restoring renal hyperfiltration in spite of reducing RVR.

PMID- 8573753
TI  - Current concepts of renal hemodynamics in diabetes.
AB  - Glomerular hyperfiltration has long been recognized in insulin-dependent
      diabetes, and has been more recently recognized in patients with non-insulin
      dependent diabetes mellitus as well. Experimentally, glomerular hyperfiltration
      has been shown to result from elevations in the glomerular capillary blood flow
      and the glomerular capillary hydraulic pressure (PGC). Of the hemodynamic
      determinants of hyperfiltration, it is glomerular hypertension that is most
      damaging to the glomerulus. Experimental and clinical studies have confirmed that
      antihypertensive agents that lower PGC more consistently slow the progression of
      injury than do those that fail to control glomerular hypertension. The
      pathogenesis of diabetic hyperfiltration is multifactoral. Many mediators have
      been proposed, including changes due to the altered metabolic milieu, and
      alterations in endogenous levels of such vasoactive mediators as atrial
      natriuretic peptide, endothelial-derived relaxing factor, angiotensin II,
      prostaglandins, thromboxanes, and kinins, among others. It has more recently been
      suggested that local renal tissue levels, rather than circulating levels, play
      the more profound role in hemodynamic regulation. For example, the renin
      angiotensin system (RAS) appears to be disproportionately active in the renal
      tissue, potentially explaining the renal vascular responsiveness to angiotensin
      converting enzyme inhibition despite absence of systemic RAS activation. Little
      is yet known of the mechanisms by which glomerular hypertension leads to injury.
      Innovative new in vitro systems have been developed to address this question.
      These studies postulate that glomerular hemodynamic factors (shear stress,
      pulsatile flow) modify the growth and activity of glomerular component cells,
      inducing the expression of cytokines and other mediators, which then stimulate
      matrix production and promote structural injury.

PMID- 8573754
TI  - Natural history of early diabetic nephropathy: what are the effects of
      therapeutic intervention? Melbourne Diabetic Nephropathy Study Group.
AB  - Several studies have shown that lowering of blood pressure slows the rate of
      progression of diabetic renal disease. Some placebo-controlled studies have also
      shown that angiotensin-converting enzyme (ACE) inhibitors decrease or stabilize
      albuminuria in incipient nephropathy and slow the rate of progression of advanced
      nephropathy. However, it is not yet clear if prolonged treatment with ACE
      inhibitors or with other agents exerts a specific renoprotective effect in
      incipient diabetic nephropathy. It is proposed that such an effect should be
      independent from changes in systemic blood pressure and should be characterized
      by amelioration of the rate of rise of albumin excretion rate (AER) and the rate
      of fall of glomerular filtration rate (GFR) and independence from changes in
      other parameters known to influence AER (glycemic control, protein intake, sodium
      intake). In addition, there should be evidence that the potentially reversible
      effects of therapeutic intervention on AER and GFR are translated to long-term
      changes in renal function and structure. This paper reviews the evidence on which
      the concept of renoprotection is based, with particular reference to choice of
      end points, heterogeneity of study groups, and complexities of the disease
      process, and relates this evidence to the natural history of nephropathy in type
      I and type II diabetes. Based on the above, an assessment is made of the
      comparative effects of ACE inhibitors and other antihypertensive agents on AER
      and GFR. It is suggested that longitudinal intra-individual analysis of both
      variables may be necessary in order to determine whether ACE inhibitors exert
      greater renoprotection than calcium channel blockers or other antihypertensive
      agents.

PMID- 8573755
TI  - Effects of intensification of antihypertensive care in diabetic nephropathy.
AB  - The overall quality of antihypertensive care in diabetic patients in Germany is
      poor. Only a minority of unselected hypertensive patients reach permanent
      normotensive blood pressure control. Previously, we have shown in a prospective
      randomized 3-year follow-up study in essential hypertension that implementation
      of a hypertension teaching and treatment program into routine care results in a
      significant improvement of blood pressure control. Subsequently, we have
      performed a prospective, controlled 5-year follow-up trial in hypertensive type I
      diabetic patients with nephropathy. One-half of a sequential sample of about 100
      hypertensive patients with overt nephropathy participated in the program based on
      blood pressure self-monitoring with the goal of normalization of blood pressure
      values below 140/90 mm Hg (intensified care, IC). The remaining patients followed
      routine antihypertensive therapy and formed the control group (routine care, RC).
      During 5 years of follow-up in IC group patients, blood pressure control was
      significantly improved. The occurrence of primary study end points (need for
      dialysis and death) was significantly lower in the IC group patients. In
      conclusion, in patients with diabetic nephropathy, participation in a
      hypertension teaching treatment program results in a long-term improvement of
      blood pressure control and a decrease in mortality and morbidity.

PMID- 8573756
TI  - Diabetic vascular hypertrophy and albuminuria: effect of angiotensin converting
      enzyme inhibition.
AB  - The role of angiotensin-converting enzyme (ACE) inhibition with ramipril on
      mesenteric vascular hypertrophy and urinary albumin excretion was explored in a
      normotensive model of experimental diabetes. Serial measurements of albuminuria
      were performed in Sprague-Dawley control, diabetic rats, and diabetic rats
      treated with ramipril. Over 24 weeks, urinary albumin excretion showed a
      continuous rise in the untreated diabetic rats. Ramipril prevented the increase
      in albuminuria over the whole study period. After 6 months, animals were perfused
      with glutaraldehyde and sacrificed for measurement of mesenteric vessel
      wall/lumen ratio and kidney weight. Diabetes was associated with increased
      mesenteric wall/lumen ratio and kidney weight. ACE inhibition, despite no effect
      on glycemic control, attenuated mesenteric vascular hypertrophy but did not
      decrease kidney weight. In addition to the well-described renoprotective effects
      of ACE inhibition in diabetes, this class of agents may have a favorable effect
      on diabetic vascular disease.

PMID- 8573757
TI  - Microalbuminuria cannot predict cardiovascular death in Japanese subjects with
      non-insulin-dependent diabetes mellitus.
AB  - In order to examine whether the existence of microalbuminuria can predict the
      development of overt proteinuria and cardiovascular death in Japanese subjects
      with non-insulin-dependent diabetes mellitus (NIDDM), we investigated 47 patients
      for a 10-year follow-up period. Patients were divided into two groups by the
      initial values of urinary albumin excretion rates. The percentage of patients who
      developed overt proteinuria during the follow-up period was significantly higher
      in patients who were initially classified as microalbuminuric group (63.6%) than
      in normoalbuminuric group (17.4%). During the follow-up period, one of the
      patients with normoalbuminuria had died of congestive heart failure, while four
      of those with microalbuminuria had died; one of stroke and three from
      noncardiovascular diseases. These results indicate that the existence of
      microalbuminuria had the predictive power for the development of overt
      proteinuria, but not for cardiovascular death in Japanese subjects with NIDDM.

PMID- 8573758
TI  - Effect of AVP.V1-receptor antagonist on urinary albumin excretion and renal
      hemodynamics in NIDDM nephropathy: role of AVP.V1-receptor.
AB  - We examined the effect of an orally effective, nonpeptide AVP.V1-receptor
      antagonist, OPC21268, on urinary albumin excretion and renal hemodynamics in non
      insulin dependent diabetes mellitus (NIDDM) patients (seven patients with
      microalbuminuria, four with overt nephropathy, and three with normoalbuminuria)
      and in three normal subjects. The oral administration of 100 mg of OPC21268,
      which is sufficient to suppress the vasoconstriction induced by exogenously
      infused AVP, caused a significant decrease in urinary albumin excretion only in
      NIDDM with microalbuminuria concomitantly with a slight decrease in filtration
      fraction and glomerular filtration rate (GFR). On the other hand, urinary beta 2
      microglobulin excretion did not change at all during the study. Neither change in
      systemic blood pressure, in heart rate, nor in plasma vasoactive substance levels
      (ANP, renin activity, aldosterone, and AVP) was observed in all four groups. In
      conclusion, in NIDDM patients with microalbuminuria, an increase in the
      sensitivity of contraction of glomerular efferent arterioles via an activation of
      AVP.V1-receptor(s) is at least present, and AVP.V1-receptor antagonist causes a
      decrease in urinary albumin excretion due partly to decrease the intraglomerular
      capillary pressure. This compound may be useful for the treatment of NIDDM
      microalbuminuria.

PMID- 8573759
TI  - The effect of PGI2 analogue on vascular endothelial function and platelet
      aggregation in patients with NIDDM.
AB  - The effect of the short-term administration of beraprost sodium, an analogue of
      prostaglandin I2 (PGI2), on the function of vascular endothelial cells and
      platelet in non-insulin-dependent diabetes mellitus (NIDDM) patients was
      investigated. Seven nonobese NIDDM patients with microalbuminuria were recruited
      for this study. They received a dose of 20 micrograms of beraprost sodium three
      times daily for 1 month. Before and after this treatment, various factors
      concerning functions of vascular endothelial cells and platelet were measured.
      Treatment with PGI2 analogue caused a decrease in basal levels of plasma
      lipoprotein (a) from 16.8 +/- 5.3 to 13.2 +/- 4.4 mg/dL (p < 0.05),
      immunoreactive-(i)endothelin from 2.4 +/- 0.3 to 1.6 +/- 0.2 pg/mL, and i
      thrombomudulin from 9.3 +/- 3.7 to 7.9 +/- 3.0 FU/L, respectively, and caused a
      significant increase in basal plasma i-tissue type plasminogen activator (tPA)
      from 5.3 +/- 0.7 to 8.3 +/- 1.5 ng/mL (p < 0.01). This treatment also increased
      maximum response of i-tPA induced by desmopressin infusion. Platelet aggregation
      due to ADP was inhibited in five of six patients after this treatment. In
      conclusion, treatment with PGI2 analogue caused a decrease in the presumed
      promoting factors of angiopathy such as lipoprotein (a) and endothelin and an
      increase in the protecting endothelial factor of angiopathy, tissue type
      plasminogen activator in patients with NIDDM. And immunoreactive thrombomodulin
      levels which reflect the vascular endothelial cell injury tended to decrease with
      the treatment. Therefore, it is suggested that this treatment preserves the
      vascular endothelial function in diabetes.

PMID- 8573761
TI  - Microalbuminuria in prediction and prevention of diabetic nephropathy in insulin
      dependent diabetes mellitus patients.

PMID- 8573760
TI  - Prostaglandins and diabetic nephropathy.
AB  - Abnormalities of renal prostaglandins (PGs) contribute to the pathogenesis of
      diabetic nephropathy through changes in renal hemodynamics. Our recent studies
      have demonstrated that urinary excretion ratio of 6-keto-PGF1 alpha (6KF) to TXB2
      is decreased in patients with non-insulin-dependent diabetes mellitus (NIDDM). In
      the present study, we evaluated the clinical effects of some drugs on renal PG
      metabolism and diabetic nephropathy. Ozagrel, a specific thromboxane synthetase
      inhibitor, reduced urinary TXB2 excretion, resulting in the improvement of the
      decreased urinary 6KF/TXB2 ratio in NIDDM patients. Urinary albumin excretion was
      decreased and creatinine clearance (Ccr) was increased during ozagrel
      administration. The similar beneficial effect was also found in the
      administration of cilostazol, a phosphodiesteraase inhibitor, whereas a stable
      analogue of PGI2, berprost sodium, reduced urinary albumin excretion in relation
      to the reduction of platelet aggregation rate. In conclusion, the drugs
      modulating renal and platelet PGs metabolism with direction to an increase in
      6KF/TXB2 ratio and an inhibition against platelet function might be beneficial
      for the treatment of diabetic nephropathy.

PMID- 8573762
TI  - SH2 and SH3 domains: potential targets for anti-cancer drug design.
AB  - Protein-tyrosine kinases interact with a diverse group of signaling molecules
      that share common structural elements known as Src homology 2 and 3 (SH2 and SH3)
      domains. SH2 domains bind with high affinity to peptide sequences within target
      proteins that contain phosphorylated tyrosine residues, but have no affinity for
      the unphosphorylated sequence. This property allows activated tyrosine kinases to
      initiate signal transduction by recruiting downstream effectors with SH2 domains.
      SH3 domains also mediate protein-protein interaction. Target sequences for SH3
      domains are rich in proline and hydrophobic amino acids, but do not require
      phosphorylation. SH2- and SH3-mediated protein-protein interactions are required
      for the transmission of proliferative signals initiated by tyrosine kinases
      (e.g., Ras activation or stimulation of phosphatidylinositol-3' kinase activity).
      Peptidomimetic ligands based on the sequence of target proteins for SH2 and SH3
      domains may represent new lead compounds for the therapy of proliferative
      diseases that are dependent upon constitutively activated tyrosine kinases (e.g.,
      BCR/ABL in chronic myelogenous and acute lymphocytic leukemias or HER-2/Neu in
      breast and ovarian cancer.

PMID- 8573763
TI  - The effect of C5a and U46619 on the isolated, perfused human placental lobule:
      development of a method for the online estimation of tissue fluid accumulation.
AB  - A method for the automatic and simultaneous determination of perfusion pressure
      and fluid accumulation in the isolated, perfused human placental lobule is
      described. We demonstrated that the inflammatory mediator, C5a, a C5a agonist
      analogue peptide, and the thromboxane mimetic U46619 caused increased fetal
      perfusion pressure and increased tissue weight when administered via the fetal
      arterial circulation. Occlusion of the fetal venous effluent tubing caused
      significantly greater increases in tissue weight than the pharmacological agents.
      Detectable increases in tissue weight occurred within 47 +/- 3 sec (n = 21)
      following pressure increases caused by the pharmacological agents. In each case,
      the increase in tissue weight was accompanied by an increased permeability of the
      materno-fetal barrier, shown by the transfer of Evans blue albumin from the fetal
      circulation to the maternal compartment.

PMID- 8573764
TI  - Simultaneous quantification of fluoxetine, norfluoxetine, and desipramine using
      gas chromatography with nitrogen-phosphorus detection.
AB  - The combination of fluoxetine (FLU) and desipramine (DMI) has been reported to be
      useful for the treatment of depression, and these drugs are also known to undergo
      a metabolic drug-drug interaction because of their effects on cytochrome P-450
      2D6. A procedure that separates these two drugs and norfluoxetine (NFLU), the N
      demethylated metabolite of FLU, and that allows simultaneous quantification of
      their levels would be of value and has been developed in our laboratories. The
      procedure involves an initial extraction into ethyl acetate after basification of
      the homogenate. The organic phase is retained and taken to dryness; the residue
      is reconstituted in water and acetylated with acetic anhydride under slightly
      basic conditions. Ethyl acetate is then used to extract the acetylated compounds
      from the aqueous medium. The organic layer is taken to dryness and the residue
      reconstituted in toluene. An aliquot of the solution in toluene is injected
      directly into a gas chromatograph equipped with a nitrogen-phosphorus detector, a
      fused silica capillary column, and an integrator/printer. Maprotiline is added to
      the initial homogenate and carried through the procedure as the internal
      standard. The assay is rapid and sensitive and has been applied successfully to
      liver and brain tissue taken from rats treated with FLU, DMI, or the combination.

PMID- 8573765
TI  - The effects of laboratory handling procedures on naloxone-precipitated withdrawal
      behavior in morphine-dependent rats.
AB  - Previous studies of opiate dependence in our laboratory have shown that opiate
      naive (control) animals can display behaviors normally ascribed to withdrawal
      following naloxone challenge. The possibility arises that in these control rats,
      the stress of the induction of dependence, pharmacological challenge, and
      behavioral testing may result in the release of endogenous opioids such that on
      naloxone administration withdrawal behaviors are elicited. In the present study,
      we have utilized two differing experimental protocols for the induction of
      morphine dependence in rats that would represent the extremes of normal
      laboratory handling procedures and have then assessed withdrawal behaviors
      following naloxone challenge. In control animals, the results show that the
      stressors alone are insufficient to allow for the precipitation of naloxone
      induced withdrawal. However, withdrawal behavior was generally greater in the
      opiate-dependent animals in the "high" rather than the "low" stress group,
      suggesting a summation of opiate effects. Similarly, a residual effect was noted
      in the control opiate-naive animals; naloxone rather than saline (control)
      challenged rats displayed a slightly higher incidence of withdrawal behavior.
      These results stress the importance of maintaining constant laboratory protocols,
      minimizing stressful procedures, and performing appropriate controls in assessing
      opiate dependence and withdrawal.

PMID- 8573766
TI  - Simultaneous measurement of intracellular calcium and tension in vascular smooth
      muscle: validation of the everted ring preparation.
AB  - This study details and validates a method that facilitates the eversion of
      vascular smooth muscle, a preparation employed in in vitro Ca2+ fluorometric
      assays. Vascular segments of porcine coronary artery, approximately 2 cm in
      length, were sutured to portions of polyethylene tubing inserted into the lumen
      of the vessel. After being secured and stabilized by the tubing, the vessel was
      easily everted while immersed in physiological buffer. Intracellular calcium
      concentrations ([Ca2+]i) and tension were measured simultaneously in everted
      rings denuded of the endothelium. In these preparations, increases in tension
      generated by KCl and prostaglandin F2 alpha (PGF2 alpha) were accompanied by
      increases in [Ca2+]i, as measured by fura-2 fluorescence. Isoproterenol (ISO) and
      sodium nitroprusside (SNP) elicited reductions in muscle tension as well as
      [Ca2+]i in both KCl- and PGF2 alpha-contracted rings. Comparison of the
      responsiveness of everted and uneverted coronary artery rings demonstrated that,
      while fura-2 fluorescence in uneverted rings was negligible, the magnitudes of
      contraction of both preparations to KCl or PGF2 alpha were similar. The relaxant
      responses to ISO and SNP were also similar in the everted and uneverted rings
      contracted with KCl or PGF2 alpha. The data suggest that the procedure employed
      in everting vascular segments maintains the integrity of the smooth muscle, thus
      making it a suitable model for the simultaneous measurement of [Ca2+]i and
      tension.

PMID- 8573767
TI  - An interactive computer program for determining areas bounded by drug
      concentration curves using lagrange interpolation.
AB  - The LAGRAN method of Rocci and Jusko for determining the area of plasma
      concentration curves has been implemented in a user-friendly form. Drug
      concentration versus time data may be entered using the keyboard or imported in
      the form of simple text files from spreadsheets or other software. The MSDOS
      program allows prompt graphic observation of the data. The effect of selecting
      different fitting modes for each segment of the curve may be viewed interactively
      using this graphic display. Pharmacokinetic parameters that are provided by the
      program include mean residence time, variance of the residence time, plasma
      clearance, and steady-state volume of distribution.

PMID- 8573768
TI  - Mathematical modeling of the osmotic fragility of rabbit red blood cells.
AB  - The osmotic fragility (OF) test is used to determine the extent of red blood cell
      hemolysis (RBCH) produced by osmotic stress. RBCH is dependent upon cell volume,
      surface area, and functional integrity of cell membranes. The variation of cell
      lysis with stress reflects underlying cell subpopulations and their membranes'
      cytoskeletal functionality. OF was determined on blood from New Zealand white
      rabbits. The dependence of RBCH on NaCl concentration ([NaCl]) was determined
      spectrophotometrically by measuring absorbance (Abs) from hemoglobin release at
      545 nm. Abs data were fitted to the equation Abs = p3 erfc(([NaCl]--p1)/p2) where
      p3 reflects maximum RBCH, p1 measures the [NaCl] at 50% RBCH, and p2 shows the
      dispersion in [NaCl] producing the RBCH. Parameter values for control blood were
      p1 = 0.4489 +/- 0.0016; p2 = 0.0486 +/- 0.0016; and p3 = 0.4366 +/- 0.0022.
      Addition of indomethacin (9.6 micrograms/mL) produced an increased fragility in
      the RBC's characterized by increased values of p1 and p2. Normalization of the
      data to p3 did not change the values of p1 or p2. Our equation satisfactorily
      describes the variation in RBCH as a function of [NaCl]. The parameters of the
      equation can be used to quantitatively characterize Abs/[NaCl] data and compare
      pharmacological, toxicological, and pathological effects on the OF of RBC's.

PMID- 8573769
TI  - Cell layer-specific expression of cyclic nucleotide phosphodiesterases in rat
      arteries: molecular cloning using isolated cell layers from paraformaldehyde
      fixed tissues.
AB  - We describe a method for the isolation of small quantities of large poly (A)+
      mRNA from blood vessels of the rat as well as from distinct cell layers of the
      rat aorta. The poly (A)+ mRNA isolated by this method is suitable for use in
      reverse transcription polymerase chain reaction (RT-PCR) amplification of low
      abundance messages. In this method, anesthetized rats are perfused with ice-cold
      phosphate-buffered paraformaldehyde to allow for the in situ fixation of many of
      the main arteries of the rat. Following the in situ fixation of the rat
      vasculature, selected blood vessels can be removed, cleaned, and poly (A)+ mRNA
      purified. In addition, the distinct cell layers of the paraformaldehyde-fixed
      aorta can be mechanically separated and poly (A)+ mRNA purified selectively from
      each. The application of this method to the study of enzymes involved in cyclic
      nucleotide-mediated cell-signaling is illustrated by the cloning of two cyclic
      AMP phosphodiesterases from rat arteries, and from the selective amplification of
      message for these enzymes from different cell layers isolated from the rat aorta.
      This method should be applicable to determine if selected mRNAs are present in
      selected blood vessels of the rat, or within distinct cell layers of particular
      large blood vessels.

PMID- 8573770
TI  - Functions of proteins secreted by oviduct epithelial cells.
AB  - Studies on embryonic development in vitro as well as observations in vivo,
      suggested that two aspects of oviduct physiology are important for early
      development. On one side has to be considered the oviduct "environment":
      temperature, pH, osmotic pressure, nutrients, oxygen tension, free radical
      scavengers, etc. On the other, the oviduct "active components": stimulatory
      and/or regulatory molecules, supposed to finely regulate the fertilisation
      process and the first differentiative steps. While the physical environment of
      the oviduct has been under investigation for some decades, studies on oviduct
      specific molecules and their functions have only been developed much more
      recently. The amount of information on this topic, however, has rapidly reached
      the size that demands a summary. In this review the descriptive literature on
      oviduct specific proteins will be examined as a basis for illustrating the
      possible functions of these molecules. In particular their role in fertilisation
      and early embryonic cleavages will be analysed in some details. Finally a section
      is devoted to the presence and physiological significance of growth factors in
      oviduct fluid.

PMID- 8573771
TI  - Morphological study of changes in the baboon oviductal epithelium during the
      menstrual cycle.
AB  - Oviductal epithelium of the baboon, Papio cynocephalus, was studied utilizing
      light, scanning, and transmission electron microscopy. Results of counts made of
      nonciliated, ciliated, and ciliogenic cells were analyzed statistically. The
      percentages of nonciliated cells of the fimbria and ampulla during the early
      proliferative and late secretory stages of the menstrual cycle were significantly
      greater than those during the mid-proliferative and late proliferative-early
      secretory stages, due to deciliation. This paper emphasizes previously unreported
      apical surface morphology as viewed by scanning and transmission electron
      microscopy. The microvillar pattern of the fimbrial secretory cells differs from
      that of the ampullar and isthmic cells in that the microvilli originate from
      thick apical protrusions and vary greatly in length and number as related to the
      cycle. A ridge demarcating the apical intercellular junction is composed of rows
      of microvilli during the early proliferative and late secretory stages. During
      the early proliferative and late secretory stages an increased degree of
      invagination of the basal and lateral plasma membranes occurs as the height and
      width of the cells decreases. The general numbers and distribution of the
      organelles of the various types of oviductal cells agree with that described for
      the ampulla and isthmus by Verhage et al. [(1990) Am. J. Anat., 187:81-90];
      however, fimbrial epithelium was not included in that study. Other cyclic
      ultrastructural changes not examined previously include variation in the number
      of lipid droplets and their location, and in the number and relationships of
      glycogen particles to other structures.

PMID- 8573772
TI  - Ultrastructure and histochemistry of acid mucus glycoproteins in the estrous
      mammal oviduct.
AB  - The mucous surfaces of the oviducts of mammals, especially humans, are dependent
      on estradiol. The mucus glycoproteins and glycocalyceal glycoproteins have,
      however, barely been studied. Biochemical analyses have focussed on the
      relatively low molecular weight glycoproteins likely to be found in more serous
      type granules of the ampulla and not on the very high MW glycoproteins typical of
      mucus and represented in the isthmus by morphological evidence of mucus
      secretion. Quantitatively, secretion from the ampulla is likely to predominate,
      because of its huge surface area compared with the isthmus. But functional
      closure of the isthmus under the influence of estradiol in the absence of
      progesterone means that it is the isthmus where luminal secretions accumulate-
      and where mucus glycoproteins will exert their most important effects on
      spermatozoa ascending the reproductive tract, and then on fertilized ova en route
      to the uterus. Further study of the extracellular, intraluminal, carbohydrate
      rich environment of the oviductal isthmus, especially in humans, is likely to
      prove rewarding. Sampling of these secretions is now feasible using transvaginal,
      transuterine fallopian tube catheters that are in clinical use.

PMID- 8573773
TI  - Co-culture of the early human embryo: factors affecting human blastocyst
      formation in vitro.
AB  - Co-culture systems have been designed to overcome the embryonic developmental
      arrest observed in vitro in conventional culture media. Oviduct and uterine
      epithelial cells can sustain embryonic development, as can trophoblastic tissue
      and transport epithelia of non-genital origin. Its benefits involve neither
      hormone dependency nor histo-specificity. Fibroblasts do not overcome the
      developmental arrest in most mammalian species, but whether they do in humans is
      still unsure. In all systems, the quality of the feeder cells and the co-culture
      medium are very important. Using the Vero cell line, 60% of human IVF embryos
      reach the blastocyst stage. The quality of the sperm seems to affect results. We
      have observed: For 10% of the patients with unexplained fertility, blastocyst
      stage is not attained; this probably involves a maternal (ovarian) problem. When
      at least one blastocyst is transferred, the pregnancy rate per transfer is 31%.
      The implantation rate in pregnant women is higher than after transfer at day 2.
      After repeated failures of transfer at early stages (2-6 cells), transfer at the
      blastocyst stage gives high pregnancy rates (40%). This indicates an in vitro
      selection. There is a strong paternal effect on blastocyst formation: poor
      quality sperm give lower rates of blastocyst. Co-culture helps to understand
      treatment failures related to male factors. Around 60% of the patients having
      spare embryos have had blastocysts frozen. Transfers of frozen-thawed blastocysts
      give a 20% pregnancy rate and an implantation rate per embryo of 11%. Co-culture
      is a new tool which has to be carefully evaluated in human IVF programs. It does
      not impair "a minima" embryo viability and it allows in vitro selection.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8573774
TI  - A human oviduct-specific glycoprotein: synthesis, secretion, and localization
      during the menstrual cycle.
AB  - The major objective of this study was to examine the hormonal regulation of a
      human oviduct-specific glycoprotein (huOGP) throughout the menstrual cycle and in
      all regions of the human oviduct. Regulation of synthesis and secretion was
      examined at both the protein (Western immunoblots and immunocytochemistry) and
      mRNA (Northern and slot blots) levels and correlated with changes in the
      morphological features of the oviductal epithelial cells throughout the cycle.
      Immunoblot analysis of oviductal fluid and explant culture media from all regions
      of the oviduct demonstrated that huOGP is primarily found during the follicular
      stage of the cycle and is not present in serum, follicular fluid, or uterine
      endometrium. Moreover, two-dimensional (2-D) immunoblots showed that all major
      isoelectric variants of huOGP observed on 2-D fluorographs are immunologically
      related. Light microscopic immunocytochemistry localized huOGP to oviductal
      secretory cells in both ampulla and isthmic regions, with the most intense
      immunoperoxidase staining seen in midcycle samples. Using an indirect immunogold
      technique at the electron microscopic level, huOGP was specifically localized to
      secretory granules of the ampullary and isthmic nonciliated epithelial cells. The
      ultrastructural characteristics of these secretory cells during the mid to late
      follicular phase of the cycle suggested elevated protein synthetic activity. In
      addition, mRNA expression for huOGP was elevated in all regions of the oviduct in
      midcycle specimens. Collectively, these data indicate that huOGP is a major
      tissue-specific, stage-specific secretory product of the human oviduct during the
      periovulatory stage of the cycle and support the hypothesis that huOGP synthesis
      and secretion may be regulated by fluctuations in the levels of estrogen and
      progesterone.

PMID- 8573775
TI  - Method for jet polishing two-phase materials.
AB  - A two-stage jet polishing technique is described which, utilising the effects of
      the characteristic current-voltage behaviour of electropolishing solutions, can
      produce excellent TEM foils of relatively coarse two-phase materials.

PMID- 8573776
TI  - Microwave oven heating enhances the ultrastructural detection of antigens in
      bioacryl-embedded tissue sections.

PMID- 8573777
TI  - Interpreting MHC class I expression and class I/class II reciprocity in the CNS:
      reconciling divergent findings.
AB  - MHC-restricted T cells are thought to contribute to clinical demyelination in MS
      and other circumstances. The step-by-step mechanisms involved and ways of
      controlling them are still being defined. Identification of the MHC+ cells in the
      CNS in situ has been controversial. This chapter reviews MHC expression in neural
      tissue, including normal, pathological, experimental, and developing tissue in
      situ and isolated cells in vitro. A basic pattern is defined, in which MHC
      expression is limited to nonneural cells and strongest class I and II expression
      are on different cell types. Variations from the basic pattern are reviewed. Ways
      of reconciling divergent findings are discussed, including the use of "mock
      tissue" to help choose between technical and biological bases for divergent
      findings, the potential contribution of internal antigen to the in situ staining
      patterns, and the possibility that class I upregulation is actively suppressed in
      situ. Functional implications of the observed patterns of MHC expression and ways
      of confirming the function of each MHC+ cell type in situ are described. It is
      suggested that modulating MHC expression in different cell types at different
      times or in different directions might be desirable.

PMID- 8573778
TI  - Dysmyelination in class I MHC transgenic mice.
AB  - Why is it that oligodendrocytes do not normally express major histocompatibility
      complex (MHC) molecules? To examine the effect of aberrant MHC expression in
      oligodendrocytes, transgenic mice have been produced which expressed the class I
      MHC gene, H-2Kb, under direction of the MBP promoter [Turnley et al. (1991b)
      Nature, 353:566-569; Yoshioka et al. (1991) Mol. Cell. Biol., 11:5479-5486]. A
      proportion of these mice exhibited a shivering phenotype, with tonic seizures and
      early death. Oligodendrocyte function and viability was shown to be affected,
      resulting in severe dysmyelination of the CNS. Is this phenomenon of cell damage
      due to aberrant expression of MHC molecules restricted to oligodendrocytes, and
      could other, non-MHC molecules, when aberrantly expressed, result in similar cell
      damage? This paper discusses these questions and examines possible mechanisms for
      the oligodendrocyte damage and hypomyelination observed in these transgenic mice.
      Finally, the implications of aberrant MHC expression in oligodendrocytes for
      demyelinating diseases such as multiple sclerosis are discussed.

PMID- 8573779
TI  - Reconstruction of the glia limitans by sub-arachnoid transplantation of astrocyte
      enriched cultures.
AB  - Lesions in CNS white matter involving loss of glial cells with concurrent
      destruction of the glia limitans lead to widespread remyelination of CNS axons by
      Schwann cells. Previous studies have demonstrated that this situation can be
      changed by transplanting cultured CNS glial cells into lesions early on in the
      repair process. In this study we have transplanted cultured astrocytes into the
      sub-arachnoid space above such a lesion in order to (1) influence the normal
      repair process by transplant-assisted reconstruction of the glia limitans, and
      (2) explore the potential of a minimally invasive route for introducing cells to
      white matter lesions. In some cases, it proved possible to influence normal
      repair by transplanting cells via the sub-arachnoid route, although the results
      were inconsistent. However, the experiment permitted observations to be made on
      the migration of transplanted astrocytes across the surface of and within the
      spinal cord.

PMID- 8573780
TI  - Progressive multifocal leukoencephalopathy: a review of the pathology and
      pathogenesis.
AB  - Progressive multifocal leukoencephalopathy is an important viral opportunistic
      infection of oligodendrocytes leading to direct demyelination. Virus is likely
      disseminated to the brain via the blood. However, the timing of that
      dissemination with relationship to clinical disease is unknown. Important clues
      about viral pathogenesis have been learned by applying molecular in situ
      techniques to diseased brain. The oligodendrocyte is the primary target for JC
      virus infection, and its death is the primary reason for demyelination. Bizarre
      astrocytes show limited viral DNA replication but are abortively infected.
      Although lymphoid organs can be infected by JC virus, there is no definitive
      evidence that lymphoid cells carry virus into the brain at the time of
      immunosuppression. JC virus may be reactivated from a latent state in both the
      brain and in non-central nervous system (CNS) organs at the time of
      immunosuppression, leading to clinical disease. Future sensitive in situ studies
      will likely resolve controversies about pathogenesis.

PMID- 8573781
TI  - Quantification of particle sizes with metal replication under standard freeze
      etching conditions: a gold ball standard for calibrating shadow widths was used
      to measure freeze-etched globular proteins.
AB  - The real size of platinum-carbon (Pt-C) replicated particles is not directly
      equivalent to either its metal-coated diameter or its shadow width. This paper
      describes two indirect methods, shadow widths and coated particle diameters, for
      determining a particle's actual size beneath a Pt-C replication film. Both
      produce equivalent measurements using the same standardized conditions: 2.3 nm Pt
      C films deposited at a 45 degree angle on an approximately -100 degrees C surface
      in a 10(-6) torr vacuum. For the first method, gold balls nucleated in a partial
      pressure of helium and deposited on flat indirect carbon films (root mean square
      roughness of 0.8 nm) on 400 mesh grids were used as test particles for
      calibrating shadow widths as a function of particle size. The gold ball test
      specimens were replicated, and a distribution of Pt-C shadow widths orthogonal to
      the Pt-C deposition direction was measured and averaged for gold balls 1.5 +/-
      0.25 nm, 2.0 +/- 0.25 nm, etc. The diameter of each gold ball was measured within
      the Pt-C film along with its shadow width because the Pt-C did not obscure or
      adhere well to the gold. The shadow width distributions for each gold size do not
      differ significantly from log normal. Two proteins, the lactose repressor and the
      mitochondrial ATPase, F1, were also used as replication test objects. Negative
      staining of both proteins was conducted to measure their average diameters. In
      the second method, a distribution of Pt-C-coated lac repressor diameters
      perpendicular to the shadow direction was measured. The Pt-C film thickness
      measured on the quartz crystal monitor was subtracted from the average metal
      coated protein diameter to obtain the lac repressor's diameter. The Pt-C-coated
      particle diameter distributions also did not differ significantly from log
      normal. While doing this work it was discovered that outgassing the Pt-C electron
      gun greatly affected Pt-C film granularity: 19 sec produced a high contrast,
      granular Pt-C film, whereas 120 sec yielded a low contrast, less granular Pt-C
      film. Both gold balls and protein particles were subjected in separate
      experiments to either 19 or 120 sec of outgassing of the Pt-C gun prior to Pt-C
      replication. Outgassing had a profound effect on the average size of the Pt-C
      shadow widths on both gold and protein particles. The Pt-C gun outgassing
      procedure also determined the smallest replicated particle that could be
      resolved. The frequency of some smaller gold ball sizes detected after
      replication was reduced disproportionately with 19 sec vs. 120 sec outgassing.
      However, Pt-C gun outgassing did not affect the average measured diameter of the
      Pt-C-coated protein particles. The "geometric assumption" that each metal-coated
      particle creates a shadow width the same size as the metal-coated particle
      diameter was tested using a globular protein. Pt-C replication of protein
      particles at a 45 degree and 20 degree angle could not confirm the geometric
      assumption because an average shadow width was always significantly larger than
      its average Pt-C-coated particle diameter. A model for how the large shadow
      widths are formed is presented. Gold balls were also replicated at a 45 degree
      angle with current high resolution conditions at a substrate temperature of -185
      degrees C, and the results of these replicas were compared to the results
      reported here at approximately -100 degrees C.

PMID- 8573782
TI  - Computer networked scanning electron microscope for teaching, research, and
      industry applications.
AB  - A laboratory designed for teaching the operation of a scanning electron
      microscope (SEM) has been developed. The laboratory makes use of a computer
      network to allow remote operation of the SEM. Movable teaching stations,
      consisting of a computer, TV monitor, and joystick control, enable students to
      view the image on the SEM screen, move the sample, control the basic operating
      parameters of the microscope, and acquire X-ray spectra. Images can also be
      stored on the computers for image analysis or incorporation into reports. The
      great advantage of the system is that it has been designed to be flexible enough
      to allow operation from any location that has access to the Internet. The system
      is relatively inexpensive and uses nonproprietary computer technology available
      at any computer store. While the laboratory has been designed for teaching, the
      concept of a multiuser SEM facility that is inexpensive and easy to install
      should have applications in both industrial and research settings.

PMID- 8573783
TI  - Freeze-fracture, deep-etch, and freeze-substitution studies of olfactory
      epithelia, with special emphasis on immunocytochemical variables.
AB  - Freeze-fracturing and deep-etching are a well-suited set of methods to study
      membrane and cytoplasmic features. Various approaches are available. Possible
      variables include tissue preparation, fracturing only or fracturing followed by
      etching, modes and materials of replication, and various ways of combining freeze
      fracturing and/or deep-etching with (immuno)cytochemistry. Freeze-substitution,
      in particular combined with embedding in methacrylate resins such as the
      Lowicryls, is becoming rather widely accepted for purposes of ultrastructural
      (immuno)cytochemistry. Most investigators active in this field agree that this
      combination yields superior results compared to (immuno)cytochemistry combined
      with more conventional means of thin section transmission electron microscopy.
      Yet relatively little information is available on the variations that can occur
      with different approaches of freeze-substitution immunocytochemistry. This review
      deals with some of the variations in freeze-fracturing, freeze-etching, and
      freeze-substitution as applied to olfactory epithelial structures and with the
      effectiveness of observations obtained by application of the above sets of
      methods in relating the special morphology of olfactory epithelial cellular
      structures with those obtained by other approaches. Indeed, the data obtained
      continue to provide an integral image in which that morphology can be related to
      the special biochemistry, cell and molecular biology, and electrophysiology of
      olfactory epithelial structures.

PMID- 8573784
TI  - Comparison of different drying procedures for scanning electron microscopy using
      human leukocytes.
AB  - Using human leukocytes as test specimens, three different drying procedures for
      scanning electron microscopy: critical-point drying (CPD), Peldri II, and
      tetramethylsilane (TMS), were compared. All three procedures produced identical
      surface morphology preservation. An equal amount of volume shrinkage was observed
      regardless of the dehydrants and drying techniques employed. Considering the
      simplicity, convenience, and time saved, air-drying with TMS is by far the best
      choice for preparing animal cells for scanning electron microscopy.

PMID- 8573785
TI  - The actin-related protein Act3p of Saccharomyces cerevisiae is located in the
      nucleus.
AB  - Actin-related proteins, a group of protein families that exhibit about 50%
      sequence identity among each other and to conventional actin, have been found in
      a variety of eukaryotic organisms. In the budding yeast Saccharomyces cerevisiae,
      genes for one conventional actin (ACT1) and for three actin-related proteins
      (ACT2, ACT3, and ACT5) are known. ACT3, which we recently discovered, is an
      essential gene coding for a polypeptide of 489 amino acids (Act3p), with a
      calculated molecular mass of 54.8 kDa. Besides its homology to conventional
      actin, Act3p possesses a domain exhibiting weak similarity to the chromosomal
      protein HMG-14 as well as a potential nuclear localization signal. An antiserum
      prepared against a specific segment of the ACT3 gene product recognizes a
      polypeptide band of approximately 55 kDa in yeast extract. Indirect
      immunofluorescence experiments with this antiserum revealed that Act3p is located
      in the nucleus. Nuclear staining was observed in all cells regardless of the
      stage of the cell cycle. Independently, immunoblotting experiments with
      subcellular fractions showed that Act3p is indeed highly enriched in the nuclear
      fraction. We suggest that Act3p is an essential constituent of yeast chromatin.

PMID- 8573786
TI  - Ionic milieu controls the compartment-specific activation of pro-opiomelanocortin
      processing in AtT-20 cells.
AB  - Newly synthesized prohormones and their processing enzymes transit through the
      same compartments before being packaged into regulated secretory granules.
      Despite this coordinated intracellular transport, prohormone processing does not
      occur until late in the secretory pathway. In the mouse pituitary AtT-20 cell
      line, conversion of pro-opiomelanocortin (POMC) to mature adrenocorticotropic
      hormone involves the prohormone convertase PC1. The mechanism by which this
      proteolytic processing is restricted to late secretory compartments is unknown;
      PC1 activity could be regulated by compartment-specific activators/inhibitors, or
      through changes in the ionic milieu that influence its activity. By arresting
      transport in a semi-intact cell system, we have addressed whether metabolically
      labeled POMC trapped in early secretory compartments can be induced to undergo
      conversion if the ionic milieu in these compartments is experimentally
      manipulated. Prolonged incubation of labeled POMC trapped in the endoplasmic
      reticulum or Golgi/trans-Golgi network did not result in processing, thereby
      supporting the theory that processing is normally a post-Golgi/trans-Golgi
      network event. However, acidification of these compartments allowed effective
      processing of POMC to the intermediate and mature forms. The observed processing
      increased sharply at a pH below 6.0 and required millimolar calcium, regardless
      of the compartment in which labeled POMC resided. These conditions also resulted
      in the coordinate conversion of PC1 from the 84/87 kDa into the 74-kDa and 66-kDa
      forms. We propose that POMC processing is predominantly restricted to acidifying
      secretory granules, and that a change in pH within these granules is both
      necessary and sufficient to activate POMC processing.

PMID- 8573787
TI  - Matrix metalloproteinases are expressed during ductal and alveolar mammary
      morphogenesis, and misregulation of stromelysin-1 in transgenic mice induces
      unscheduled alveolar development.
AB  - The matrix-degrading metalloproteinases stromelysin-1, stromelysin-3, and
      gelatinase A are expressed during ductal branching morphogenesis of the murine
      mammary gland. Stromelysin-1 expression in particular correlates with ductal
      elongation, and in situ hybridization and three-dimensional reconstruction
      studies revealed that stromelysin-1 mRNA was concentrated in stromal fibroblasts
      along the length of advancing ducts. Transgenic mice expressing an activated form
      of stromelysin-1 under the control of the MMTV promoter/enhancer exhibited
      inappropriate alveolar development in virgin females. Ultrastructural analysis
      demonstrated that the basement membrane underlying epithelial and myoepithelial
      cells was amorphous and discontinuous compared with the highly ordered basal
      lamina in control mammary glands. Transgenic mammary glands had at least a
      twofold increase in the number of cells/unit area and a 1.4-fold increase in the
      percent of cycling cells by 13 wk of age compared with nontransgenic littermates.
      In addition, transgenic glands expressed beta-casein mRNA, but not protein, and
      resembled the proliferative and differentiated state of an animal between 8 and
      10 days pregnant. An analysis of metalloproteinase expression in the glands of
      normal pregnant females demonstrated that the same matrix metalloproteinase
      family members, including stromelysin-1, were expressed in connective tissue
      cells surrounding epithelial clusters during the time of lobuloalveolar
      development. These results suggest that metalloproteinases may assist in
      remodeling ECM during normal ductal and alveolar branching morphogenesis, and
      that disruption of the basement membrane by an activated metalloproteinase can
      affect basic cellular processes of proliferation and differentiation.

PMID- 8573788
TI  - Beta 1 integrins signal lipid second messengers required during cell adhesion.
AB  - Clustering of integrin receptors during cell adhesion stimulates signal
      transduction across the cell membrane. Second messengers are generated,
      activating cytosolic proteins and causing cytoskeletal assembly and
      rearrangement. HeLa cell adhesion to a collagen substrate has been shown to
      initiate an arachidonic acid-mediated signaling pathway, leading to the
      activation of protein kinase C (PKC) and cell spreading. To determine the role of
      integrin receptors in triggering this signaling pathway, monoclonal antibodies to
      beta 1 integrins were used to either cluster integrins on the cell surface or to
      provide an integrin-dependent substrate for cell adhesion. Using this approach,
      we have defined a pathway required for cell spreading that can be initiated by
      the ligation of integrins and leads to the activation of PKC. Specifically, our
      results indicate that clustering beta 1 integrins results in the activation of
      phospholipase A2 leading to the production of arachidonic acid and the activation
      of PKC.

PMID- 8573789
TI  - The organization of the endoplasmic reticulum and the intermediate compartment in
      cultured rat hippocampal neurons.
AB  - The boundaries of the organelles of the biosynthetic endomembrane system are
      still controversial. In this paper we take advantage of the unique architectural
      organization of neurons to investigate the localization of a spectrum of
      compartment-specific markers with the goal of defining the location of the rough
      endoplasmic reticulum (ER), smooth ER, intermediate compartment, and the Golgi
      complex. Markers of the rough ER (signal sequence receptor), Golgi complex
      (mannosidase II), and the trans Golgi network (TGN38) were essentially restricted
      to the cell body and the initial segment of one of the cell's dendrites. In
      contrast the cytochemical reaction product for glucose 6 phosphate, a classical
      ER marker, in addition to staining ER structures in the cell body also reacted
      with smooth ER elements that extended into both axons and dendrites. These
      peripheral smooth ER elements also reacted at the immunofluorescence level for ER
      marker 3-hydroxy-3-methylglutaryl-coenzyme A reductase, as well as for calnexin
      and protein disulfide isomerase. We also analyzed the location of rab1, rab2,
      p58, the KDEL receptor, and beta-subunit of coatomer. These intermediate
      compartment markers were found predominantly in the cell body but also extended
      to the proximal parts of the dendrites. Collectively, our data argue that the ER
      of hippocampal neurons consists of functionally and spatially distinct and
      separated domains, and they stress the power of the hippocampal neuron system for
      investigations of the organization of the ER by light microscopy.

PMID- 8573790
TI  - Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and
      phosphorylates Drosophila Cdc2 in vitro.
AB  - Cdc2 kinase activity is required for triggering entry into mitosis in all known
      eukaryotes. Elaborate mechanisms have evolved for regulating Cdc2 activity so
      that mitosis occurs in a timely manner, when preparations for its execution are
      complete. In Schizosaccharomyces pombe, Wee1 and a related Mik1 kinase are Cdc2
      inhibitory kinases that are required for preventing premature activation of the
      mitotic program. To identify Cdc2-inhibitory kinases in Drosophila, we screened
      for cDNA clones that rescue S. pombe wee1- mik1- mutants from lethal mitotic
      catastrophe. One of the genes identified in this screen, Drosophila wee1 (Dwee1),
      encodes a new Wee1 homologue. Dwee1 kinase is closely related to human and
      Xenopus Wee1 homologues, and can inhibit Cdc2 activity by phosphorylating a
      critical tyrosine residue. Dwee1 mRNA is maternally provided to embryos, and is
      zygotically expressed during the postblastoderm divisions of embryogenesis.
      Expression remains high in the proliferating cells of the central nervous system
      well after cells in the rest of the embryo have ceased dividing. The loss of
      zygotically expressed Dwee1 does not lead to mitotic catastrophe during
      postblastoderm cycles 14 to 16. This result may indicate that maternally provided
      Dwee1 is sufficient for regulating Cdc2 during embryogenesis, or it may reflect
      the presence of a redundant Cdc2 inhibitory kinase, as in fission yeast.

PMID- 8573791
TI  - Convergence of integrin and growth factor receptor signaling pathways within the
      focal adhesion complex.
AB  - Extracellular matrix controls capillary endothelial cell sensitivity to soluble
      mitogens by binding integrin receptors and thereby activating a chemical
      signaling response that rapidly integrates with growth factor-induced signaling
      mechanisms. Here we report that in addition to integrins, growth factor receptors
      and multiple molecules that transduce signals conveyed by both types of receptors
      are immobilized on the cytoskeleton (CSK) and spatially integrated within the
      focal adhesion complex (FAC) at the site of integrin binding. FACs were rapidly
      induced in round cells and physically isolated from the remainder of the CSK
      after detergent-extraction using magnetic microbeads coated with fibronectin or a
      synthetic RGD-containing peptide. Immunofluorescence microscopy revealed that
      multiple signaling molecules (e.g., pp60c-src, pp125FAK, phosphatidylinositol-3
      kinase, phospholipase C-gamma, and Na+/H+ antiporter) involved in both integrin
      and growth factor receptor signaling pathways became associated with the CSK
      framework of the FAC within 15 min after binding to beads coated with integrin
      ligands. Recruitment of tyrosine kinases to the FAC was also accompanied by a
      local increase in tyrosine phosphorylation, as indicated by enhanced
      phosphotyrosine staining at the site of integrin binding. In contrast, neither
      recruitment of signaling molecules nor increased phosphotyrosine staining was
      observed when cells bound to beads coated with a control ligand (acetylated low
      density lipoprotein) that ligates transmembrane scavenger receptors, but does not
      induce FAC formation. Western blot analysis confirmed that FACs isolated using
      RGD-beads were enriched for pp60c-src, pp125FAK, phospholipase C-gamma, and the
      Na+/H+ antiporter when compared with intact CSK or basal cell surface
      preparations that retained lipid bilayer. Isolated FACs were also greatly
      enriched for the high affinity fibroblast growth factor receptor flg. Most
      importantly, isolated FACs continued to exhibit multiple chemical signaling
      activities in vitro, including protein tyrosine kinase activities (pp60c-src and
      pp125FAK) as well as the ability to undergo multiple sequential steps in the
      inositol lipid synthesis cascade. These data suggest that many of the chemical
      signaling events that are induced by integrins and growth factor receptors in
      capillary cells may effectively function in a "solid-state" on insoluble CSK
      scaffolds within the FAC and that the FAC may represent a major site for signal
      integration between these two regulatory pathways. Future investigations into the
      biochemical and biophysical basis of signal transduction may be facilitated by
      this method, which results in isolation of FACs that retain the CSK framework as
      well as multiple associated chemical signaling activities.

PMID- 8573792
TI  - Computer analysis of the binding reactions leading to a transmembrane receptor
      linked multiprotein complex involved in bacterial chemotaxis.
AB  - The chemotactic response of bacteria is mediated by complexes containing two
      molecules each of a transmembrane receptor and the intracellular signaling
      proteins CheA and CheW. Mutants in which one or the other of the proteins of this
      complex are absent, inactive, or expressed at elevated amounts show altered
      chemotactic behavior and the phenotypes are difficult to interpret for some
      overexpression mutants. We have examined the possibility that these unexpected
      phenotypes might arise from the binding steps that lead to active complex
      formation. A limited genetic algorithm was used to search for sets of binding
      reactions and associated binding constants expected to give mutant phenotypes in
      accord with experimental data. Different sets of binding equilibria and different
      assumptions about the activity of particular receptor complexes were tried.
      Computer analysis demonstrated that it is possible to obtain sets of binding
      equilibria consistent with the observed phenotypes and provided a simple
      explanation for these phenotypes in terms of the distribution of active and
      inactive complexes formed under various conditions. Optimization methods of this
      kind offer a unique way to analyze reactions taking place inside living cells
      based on behavioral data.

PMID- 8573793
TI  - Organelle-cytoskeletal interactions: actin mutations inhibit meiosis-dependent
      mitochondrial rearrangement in the budding yeast Saccharomyces cerevisiae.
AB  - During early stages of meiosis I, yeast mitochondria fuse to form a single
      continuous thread. Thereafter, portions of the mitochondrial thread are equally
      distributed to daughter cells. Using time-lapse fluorescence microscopy and a
      membrane potential sensing dye, mitochondria are resolved as small particles at
      the cell periphery in pre-meiotic, living yeast. These organelles display low
      levels of movement. During meiosis I, we observed a threefold increase in
      mitochondrial motility. Mitochondrial movements were linear, occurred at a
      maximum velocity of 25 +/- 6.7 nm/s, and resulted in organelle collision and
      fusion to form elongated tubular structures. Mitochondria do not co-localize with
      microtubules. Destabilization of microtubules by nocodazole treatment has no
      significant effect on the rate and extent of thread formation. In contrast, yeast
      bearing temperature-sensitive mutations in the actin-encoding ACT1 gene (act1-3
      and act1-133) exhibit abnormal mitochondrial aggregation, fragmentation, and
      enlargement as well as loss of mitochondrial motility. In act1-3 cells,
      mitochondrial defects and actin delocalization occur only at restrictive
      temperatures. The act1-133 mutation, which perturbs the myosin-binding site of
      actin without significantly affecting actin cytoskeletal structure in meiotic
      yeast, results in mitochondrial morphology and motility defects at restrictive
      and permissive temperatures. These studies support a role for the actin
      cytoskeleton in the control of mitochondrial position and movements in meiotic
      yeast.

PMID- 8573796
TI  - The forces that threaten the U.S. medical device industry.

PMID- 8573794
TI  - Cell cycle-dependent phosphorylation and microtubule binding of tau protein
      stably transfected into Chinese hamster ovary cells.
AB  - Tau protein, a neuronal microtubule-associated protein, is phosphorylated in situ
      and hyperphosphorylated when aggregated into the paired helical filaments of
      Alzheimer's disease. To study the phosphorylation of tau protein in vivo, we have
      stably transfected htau40, the largest human tau isoform, into Chinese hamster
      ovary cells. The distribution and phosphorylation of tau was monitored by gel
      shift, autoradiography, immunofluorescence, and immunoblotting, using the
      antibodies Tau-1, AT8, AT180, and PHF-1, which are sensitive to the
      phosphorylation of Ser202, Thr205, Thr231, Ser235, Ser396, and Ser404 and are
      used in the diagnosis of Alzheimer tau. In interphase cells, tau becomes
      phosphorylated to some extent, partly at these sites; most of the tau is
      associated with microtubules. In mitosis, the above Ser/Thr-Pro sites become
      almost completely phosphorylated, causing a pronounced shift in M(r) and an
      antibody reactivity similar to that of Alzheimer tau. Moreover, a substantial
      fraction of tau is found in the cytoplasm detached from microtubules.
      Autoradiographs of metabolically labeled Chinese hamster ovary cells in
      interphase and mitosis confirmed that tau protein is more highly phosphorylated
      during mitosis. The understanding of tau phosphorylation under physiological
      conditions might help elucidate possible mechanisms for the hyperphosphorylation
      in Alzheimer's disease.

PMID- 8573797
TI  - The effects of regulation, reimbursement, and product liability on U.S. medical
      technology innovation.

PMID- 8573795
TI  - RACH2, a novel human gene that complements a fission yeast cell cycle checkpoint
      mutation.
AB  - We have identified a novel human gene by virtue of its ability to complement the
      rad1-1 checkpoint mutant of Schizosaccharomyces pombe. This gene, called RACH2,
      rescues the temperature-sensitive lethality of a rad1-1 wee1-50 double mutant of
      S. pombe. Expression of RACH2 in S. pombe rad1-1 strains partially restores UV
      resistance to the rad1-1 mutant strain. Expression of RACH2 in a rad1-1 cdc25-22
      double mutant partially restores the dose-dependent delay in mitotic entry after
      irradiation that is lost in rad1-1 checkpoint-deficient mutants. Overexpression
      of RACH2 in human tissue culture cells induces apoptosis.

PMID- 8573798
TI  - Progress in the development of the ABIOMED total artificial heart.
AB  - The ABIOMED implantable total artificial hearts in the final phase of engineering
      development. The system has a compact electrohydraulically driven energy
      converter sandwiched between two blood pumps, an internal electronics pack, an
      internal battery, a transcutaneous energy transmission coil for power
      transmission, and external wearable electronics pack and battery. The current
      effort is to complete development of the system during 1996 in preparation for
      formal pre clinical testing of the device. In vivo studies with the current
      thoracic unit (ABH II) have achieved 108 days of survival verifying the thermal,
      physiologic, and hematologic compatibility of the system. The abdominal
      implantable electronics pack showed no thermal dissipation problem. System
      improvements include scaling down the size of the thoracic unit, and efficiency
      enhancement in the power and hybrid electronics. The new system (ABH III) retains
      the flow capacity of greater than 10 L/min. Size reduction results in an atrial
      to sternal dimension that would fit 98% and 75% of men and women, respectively.

PMID- 8573799
TI  - Development of an electrohydraulic total artificial heart at the National
      Cardiovascular Center, Osaka, Japan.
AB  - The authors have been developing an electrohydraulic total artificial heart with
      a basic concept placing the blood pumps and an electrohydraulic energy converter
      separately, in the thorax and the abdominal region, respectively, to minimize
      anatomic constraints. Major problems of the system were a high energy consumption
      of 56 W at 6 L/min output and an insufficient maximum output of 6.7 L/min. The
      energy converter was redesigned to overcome these problems. A three phase, 4 pole
      brushless DC motor, which has maximum efficiency of 79% at a motor rotation of
      2500 rpm with a load of 0.1 Nm, was developed for the new energy converter. Flow
      channel design of the regenerative oil pump was optimized, which resulted in
      increasing the maximum flow rate at one directional motor rotation from 18 to 29
      L/min. In vitro performance of the electrohydraulic total artificial heart was
      evaluated in a mock circulation with physiologic pressure conditions. Maximum
      output was increased to 10.7 L/min at a pump rate of 120 bpm and energy
      consumption of the motor at 6 L/min output was reduced to 18 W. Based upon these
      favorable results, the system is now being assembled for chronic animal
      implantation.

PMID- 8573801
TI  - A high capacity transcutaneous energy transmission system.
AB  - A transcutaneous energy transmission system is described that transmits up to 60
      W for use by a mechanical circulatory support system or other internal device. It
      contains an input power conditioning circuit that permits it to sustain the
      required output with input voltages ranging from 10 to 16 V. The transcutaneous
      energy transmission system demonstrated a best overall efficiency of 77% when
      connected to a resistive load and 74% when connected to a mechanical circulatory
      support system pumping up to 8.0 L/min to a mock circulation system. These
      figures included the losses in the conditioning circuit, which, when operated
      separately, had an efficiency of 94%. By tuning the resonant frequency of the
      primary, an output with only a 10% variation was achieved with coils separated by
      between 0 and 25 mm. A model of the inductively coupled resonant circuits was
      analyzed and a closed form solution obtained that verified the equations reported
      by Galbraith et al. Additional useful results obtained included an expression for
      the efficiency of the power transfer through the coupled circuits and the ratio
      of the current circulating in the primary and secondary coils. These results
      indicate that information useful for control of the output voltage of the
      secondary may be available in the primary circuit.

PMID- 8573800
TI  - A transcutaneous energy and information transfer system for implanted medical
      devices.
AB  - During the last four decades there has been a rapid increase in the development
      and usage of medical devices. Currently, there are more than 500,000 devices on
      the market and 25,000 new devices enter the market each year. Many medical
      devices are now designed to be implantable (pacemakers, defibrillators,
      circulatory assist devices, artificial hearts, cochlear implants, neuromuscular
      stimulators, biosensors, etc.). Almost all of the active devices (those that
      perform work) and many of the passive devices (those that do not perform work)
      require a source of power. In addition, these devices need to be monitored and
      controlled, which can be accomplished by utilizing remote communication methods.
      A transcutaneous energy transfer system combined with a remote communications
      system has been developed and evaluated in vitro and in vivo (bovine, porcine,
      and human cadaver experiments). The energy transfer system can deliver up to 60 W
      with power transfer efficiencies between 60 and 83%. An automatically tuned,
      resonant frequency tracking method is used to obtain optimum power transfer over
      a range of operating conditions. The remote communications system can transfer
      digital data bidirectionally through intact skin at rates up to 9600 baud. The
      system transmits information by frequency modulating an 890 nm infrared carrier
      signal. The system has demonstrated satisfactory performance during multicenter
      evaluation with ventricular assist and total artificial heart devices. Design
      improvements have been identified, which will be implemented to produce an
      optimized system for energy transfer to and remote communications with various
      implantable medical devices.

PMID- 8573802
TI  - Assessment of circulating blood volume in calves with a total artificial heart.
AB  - Measurement of the circulating blood volume (CBV) is essential to a proper
      understanding of the hemodynamic performance of total artificial hearts (TAHs).
      Recently, the authors employed CBV measurements using indocyanine green dye in
      calves with a TAH. The advantages of this method over previous methods using
      radionuclides include simplicity, low cost, and the capability of repeated and
      frequent measurements. Reproducibility of the measurements was demonstrated in
      three normal calves with a relative standard deviation of 3.9 +/- 2.4%. CBV was
      measured in eight calves with the Cleveland Clinic-Nimbus TAH and compared with
      that of seven calves that underwent mitral valve replacement. Small standard
      deviations in pre operative values in both TAH and mitral valve replacement
      groups demonstrated the precision of CBV measurements. Although there was no
      change in CBV in the mitral valve replacement group, CBV in the TAH group
      increased to more than twice the pre operative value after 2 weeks. Although the
      right atrial pressure increased similarly after TAH implantation, there was no
      correlation (r = 0.08) between the right atrial pressure and CBV, which suggested
      a possible inaccuracy in estimating CBV from the right atrial pressure. A
      negative correlation between the hematocrit value and CBV suggested that
      hemodilution might be one of the causes of anemia observed in our TAH animals.

PMID- 8573803
TI  - A comprehensive hematologic study in calves with total artificial hearts.
AB  - Thromboembolism and infection remain potential threats for long-term circulatory
      assist and replacement devices. The alteration of the hemostatic system and of
      blood cell functions caused by device implantation may predispose the recipient
      to these complications. Many sensitive coagulation assays and the technology of
      flow cytometry would be powerful tools for this investigation. The availability
      of such immunologic technologies for animal species other than humans has yet to
      be established. In a series of in vitro tests we found that the following assays,
      among others, are usable in calves: TAT, TxB2, platelet surface glycoprotein
      IIbIIIa, and membrane aminophospholipid. F1.2, D-dimer, beta TG, PF-4, and
      platelet surface expression of GMP-140 and receptors for fibronectin,
      thrombospondin, and vWF were not measurable. A sustained mild decrease in
      hematocrit levels in six calves with the Cleveland Clinic-Nimbus total artificial
      heart for 11-120 days was attributed to an increase in circulating blood volume,
      but not to red blood cell damage. Whole blood platelet aggregation was suppressed
      only for the first 3 post operative days, with decreased GPIIbIIIa expression.
      Polymorphonuclear phagocytosis, chemotaxis, and superoxide anion production were
      not altered. Device infection and thromboembolism occurred in one of 13 cases
      overall.

PMID- 8573804
TI  - Noninvasive diagnosis of mechanical failure of the implanted total artificial
      heart using neural network analysis of acoustic signals.
AB  - Acoustic signal measurement has been proposed as a noninvasive method of
      detecting mechanical failure of the implanted total artificial heart. However,
      differences in acoustic spectra obtained from undamaged and damaged devices may
      be difficult to distinguish using standard techniques, such as visual inspection
      or statistical analysis. A new technique, artificial neural network analysis,
      which has been used successfully on other problems of pattern recognition and
      classification, was applied to improve the detectability of the acoustic method.
      Acoustic signals were measured using two different devices in one damaged and one
      undamaged electrohydraulic total artificial heart, both in a mock circulation set
      up and in animal experiments where they were implanted in eight post mortem sheep
      and the acoustic signal measured using a microphone placed at the skin surface.
      Spectra of the acoustic waveforms were calculated by discrete Fourier
      transformation and 400 values (representing the log magnitude in each 2.5 Hz band
      of the spectrum between 0 and 1 kHz) and used as input to the neural network. A
      three layer backpropagation neural network containing 400 input nodes, 20
      intermediate nodes, and one output node was able to forms. The trained neural
      network then perfectly distinguished damaged waveforms from undamaged ones, with
      good separability. Because the neural network's output can take on a value
      between two extremes denoting damaged and undamaged states, it is possible to
      detect any progressive failure at relatively earlier stages. With multiple output
      node configuration, it could also classify the different types of damage using
      single acoustic signal waveforms.

PMID- 8573805
TI  - Left ventricular assist device options in pediatric patients.
AB  - Left ventricular assist devices can be successfully used in the pediatric
      population if currently available devices are used appropriately. To highlight
      their management strategies, the authors' experience with pediatric left
      ventricular assist devices is reviewed, with case studies documenting options for
      device use. A retrospective study was conducted for all patients supported at the
      authors' institutions. Nine pediatric patients received devices during this time,
      with ages ranging from 12 days to 15 years. There was considerable size
      differences in our patients, with weights ranging between 2.5 and 73 kg. Either
      the Abiomed BVS 5000 (Abiomed Cardiovascular, Inc, Danvers, MA) or the Biomedicus
      centrifugal pump (Bio-Medicus, Inc, Eden Prairie, MN) were used for all patients.
      Patients were supported for an average of 5 days (range 1-11 days). Eight
      patients were successfully weaned from the device, with four undergoing
      transplant. Four patients were discharged and are long-term survivors, and one is
      still recovering post transplant. Neurologic sequelae were the most common
      complications in these patients, with four patients having events. Pediatric
      ventricular assist devices are limited because of size considerations, although
      current devices can be successfully used for bridging to recovery or
      transplantation. New devices are needed to meet the flow and size characteristics
      for pediatric patients. Successful use of assist devices, as has been recognized
      in adults, is possible in pediatric patients if these requirements are met.

PMID- 8573807
TI  - Heat generation and hemolysis at the shaft seal in centrifugal blood pumps.
AB  - The heat and hemolysis around a shaft seal were investigated. Materials were
      original pumps (Nikkiso HMS-15:N-original, and 3M Delphin:D-original), vane
      removed pumps (Nvane(-), Dvane(-)), and a small chamber with a shaft coiled by
      nichrome wire (mock pump). The original pumps were driven at 500 mmHg and 5
      L/min, and vane-removed pumps were driven at the same rotation number. An
      electrical powers of 0, 0.5, 2, and 10 W was supplied to the mock pumps. In vitro
      hemolytic testing showed that hemolytic indices were 0.027 g/100 L in N-original,
      0.013 in Nvane(-), 0.061 in D-original, and 0.012 in Dvane(-). Measurement of
      heat with a thermally insulated water chamber showed total heat within the pump
      of 8.62 and 10.85 W, and heat at the shaft seal of 0.87 and 0.62 W in the Nikkiso
      and Delphin pumps, respectively. Hemolysis and heat generation of mock pumps
      remained low. The results indicate that the heat generated around the shaft seal
      was minimal. Hemolysis at the shaft-seal was considerable but not major. Local
      heat did not affect hemolysis. It was concluded that the shaft-seal affected
      hemolysis, not by local heat but friction itself.

PMID- 8573806
TI  - The role of the registered nurse-first assistant in the implantable left
      ventricular assist device program.
AB  - Successful support of patients using the implantable left ventricular assist
      device requires sustained and coordinated efforts by physicians and medical
      personnel. The authors describe the role of their registered nurse-first
      assistant (RNFA) as it has evolved through caring for 43 implantable pneumatic
      left ventricular assist device patients and 8 vented-electric left ventricular
      assist system patients during a 3 year period. Intraoperatively, the RNFA is
      responsible for pump assembly, including pre sealing all grafts and connecting
      areas of the pump using a combination of cryoprecipitate and thrombin. The RNFA
      assists with pump insertion during surgery. At device explantation, the RNFA
      dismantles the pump according to the FDA protocol for disassembly. Post
      operatively, the RNFA assesses and maintains patient hemodynamic stability and
      intervenes to manage hemodynamic and mechanical problems. Of the 51 patients, 13
      are still on support, 9 died before transplantation (17.6%), and post transplant
      survival is 96.0%. In conclusion, an active left ventricular assist device
      program requires skilled personnel to manage complex problems and contributes to
      a successful patient outcome.

PMID- 8573808
TI  - Normothermia has beneficial effects in cardiopulmonary bypass attenuating
      inflammatory reactions.
AB  - "Post perfusion syndrome" after cardiopulmonary bypass (CPB) has been known to be
      evoked by inflammatory reactions. To elucidate the effect of perfusate
      temperature during CPB on subsequent inflammatory reactions, serum levels of
      interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, IL-1 beta, and
      polymorphonuclear (PMN) elastase were measured before and after (0, 12 hours, and
      24 hours after) CPB in adult patients undergoing cardiac operations. Patients
      were divided into two groups: the normothermic CPB group (NOR, 34 degrees C
      perfusate temperature, n = 8) and hypothermic CPB group (HYP, 28 degrees C
      perfusate temperature, n = 8). In both groups, IL-6, IL-8, and PMN elastase
      levels were elevated during CPB, while the increase of tumor necrosis factor
      alpha and IL-1 beta was not detected. The increase in IL-8 and PMN elastase
      levels at 12 hours after CPB was significantly less in NOR than in HYP (IL-8; NOR
      versus HYP, 15.1 +/- 12.9 versus 62.5 +/- 30.6 pg/ml, p < 0.05, PMN elastase; 394
      +/- 200 versus 1085 +/- 523 micrograms/L, p < 0.05) while neither group showed
      any difference in IL-8 and PMN elastase at 24 hours after CPB. There was no
      difference in IL-6 between the two groups, and no significant increase in tumor
      necrosis factor-alpha and IL-1 beta levels were detected in either group after
      CPB. These results demonstrate that although CPB activated inflammatory reactions
      detected by IL-8 and PMN elastase activity, post operative persistence of these
      reactions were attenuated by warm CPB.

PMID- 8573810
TI  - Hepatic circulation during nonpulsatile cardiopulmonary bypass.
AB  - The arterial ketone body ratio, which reflects the hepatic mitochondrial redox
      potential (NAD+/NADH), decreases markedly during cardiopulmonary bypass (CPB).
      One of the reasons for arterial ketone body ratio reduction may be hepatic
      hypoperfusion during CPB. To evaluate the hepatic circulation under nonpulsatile
      CPB, the authors used color Doppler ultrasonography to measure the portal venous
      flow (PVF) in 24 adult patients before, during (aortic clamping and rewarming
      period), and after CPB. Nonpulsatile hypothermic CPB was performed at a flow rate
      of 2.4 L/min/m2. PVF was calculated from the product of mean flow velocity and
      cross-sectional area of the portal vein. PVF was maintained during CPB at 0.44 +/
      0.13 and at 0.54 +/- 0.18 L/min/m2. PVF (%) in relation to systemic blood flow
      was obtained by calculating PVF/CI or PVF/PI, where CI is the cardiac index and
      PI is the perfusion index. PVF (%) before, during, and after CPB was 18.3 +/-
      9.3, 18.5 +/- 5.5, and 17.4 +/- 6.7%, respectively. In conclusion, PVF was
      maintained during nonpulsatile CPB at a flow rate of 2.4 L/min/m2 and depended
      upon systemic blood flow.

PMID- 8573809
TI  - The role of leukocyte depletion in reducing injury to myocardium and lung during
      cardiopulmonary bypass.
AB  - Activated leukocytes and oxygen free radicals have been implicated in the
      pathogenesis of heart and lung injury after reperfusion and during
      cardiopulmonary bypass. This study was designed to determine whether leukocyte
      depletion prevents injury to the heart and lung during cardiopulmonary bypass.
      Twenty-eight open heart surgeries were performed in this study. In Group F,
      leukocyte depletion was performed with an LG-6 arterial line filter after aortic
      declamp (n = 14). Leukocyte depletion was not performed during cardiopulmonary
      bypass in Group C (n = 14). Thereafter, cardiac and lung function were assessed
      in the 24 hr after reperfusion. The total catecholamine dose used for 24 hr after
      reperfusion (r) was 61.9 +/- 13.4 in Group C and 43.9 +/- 19.2 in Group F (p <
      0.05). CK-MB at 3 and 6 hr after reperfusion was 65.9 +/- 13.5 and 64.8 +/- 15.8
      in Group C and 45 +/- 11.8 and 38 +/- 10.8 in Group F, respectively (p < 0.05).
      The pulmonary index after reperfusion at 3 and 6 hr was 1.7 +/- 0.5 and 1.3 +/-
      0.4 in Group C and 0.7 +/- 0.3 and 0.6 +/- 0.4 in Group F, respectively (p <
      0.05). There was significantly better preserved lung function in Group F. In
      conclusion, leukocyte depletion was significantly effective in preserving heart
      and lung function during cardiopulmonary bypass.

PMID- 8573811
TI  - Hypothermic blood substitution enables resuscitation after hemorrhagic shock and
      2 hours of cardiac arrest.
AB  - Uncontrollable hemorrhage accounts for a large proportion of total mortality in
      both civilian (31%) and military (47%) trauma victims. Hypothermia is a
      relatively safe method that could provide total body protection during
      hypovolemic shock and facilitate surgical intervention as a potentially life
      saving procedure. This study tested the hypothesis that profound hypothermia and
      complete blood replacement in an established canine model, would facilitate
      resuscitative therapy from exsanguinating hypovolemic shock. Adult dogs were
      prepared for extracorporeal bypass using closed-chest peripheral cannulation
      under general anesthesia. Controlled hypotensive, hemorrhagic shock (mean
      arterial blood pressure < 50 mmHg) was induced for 30 min at normal temperature
      followed by temporary resuscitation using crystalloid infusion for approximately
      10 min. Using our established procedure, the dogs were then cooled externally to
      27 degrees C before initiating blood substitution with Hypothermosol (Cryomedical
      Sciences, Inc. Rockville, MD) via the extracorporeal pump. The heart was arrested
      during further cooling to below 10 degrees C and Hypothermosol was recirculated
      for 2 hr, with (3 dogs) or without (5 dogs) 1 hr of circulatory arrest. During
      rewarming the animals were autotransfused, weaned from the pump, and allowed to
      recover. All dogs (n = 8) survived, all but one with complete neurologic
      recovery: blood chemistry samples examined immediately after the procedure showed
      significant differences (p < 0.05) in only a few parameters, including creatine
      kinase (CK-BB and CK-MB), compared with the previous group of control dogs. The
      consistent survival of dogs showing apparently normal neurologic, physiologic,
      and biochemical recovery supports the concept that profound hypothermia using a
      protective hypothermic blood substitute could provide time for therapeutic
      resuscitation of currently intractable trauma cases.

PMID- 8573812
TI  - A protamine filter for extracorporeal heparin removal. Development, testing,
      blood compatibility evaluation, and future direction.
AB  - The authors previously developed a filter device containing immobilized protamine
      (termed "protamine filter") that could be used to remove heparin during
      extracorporeal perfusion. In vivo studies involving dogs showed that the
      protamine filter removed more than 50% of heparin from the animals' blood circuit
      in less than 20 min. In addition, the use of the protamine filter did not elicit
      statistically significant protamine induced hemodynamic and thrombocytopenic
      responses. Biocompatibility of the protamine filter was also evaluated, with the
      focus on its effect on the coagulation cascade, the complement system, and the
      blood antithrombin III levels. Results showed that heparin adsorbed to the
      protamine coated surface retained 20% of its original activated partial
      thromboplastin time activity, rendering the coated surface antithrombotic.
      Activation of the coagulation system by the protamine coated membrane and the
      untreated cellulose membrane, as measured by the elevation of prothrombin
      fragment F1 + 2 levels, was statistically identical. The CH50 hemolytic assay
      showed that the protamine coated membrane produced a reduction of 1.2 +/- 0.8% of
      the total complement levels, as compared to 9.4 +/- 1.6% by the untreated
      membrane. In addition, the change in C3a des Arginine levels after 30 min of
      circulation was 1.5 +/- 0.2 mg/ml by the protamine filter, as compared to 2.1 +/-
      0.1 mg/ml by the untreated membrane. Unlike native heparin that would bind with
      antithrombin, heparin adsorbed on the protamine coated surface was devoid of such
      activity, and produced no depletion of circulating antithrombin. Because of the
      limited capacity of the protamine filter, the future system is envisioned to
      consist of two filters; while one filter is removing heparin the other will be
      regenerated. With a recently developed heparin sensor, it should be possible to
      design a sensor directed, biofeedback, two filter heparin removal system.

PMID- 8573813
TI  - A new porous tracheal prosthesis sealed with collagen sponge.
AB  - We have designed a new tracheal prosthesis to overcome problems with an earlier
      device, which included stenosis and exposure of its constituent mesh. A
      polypropylene mesh cylinder, reinforced with a polypropylene spiral, is sealed
      with collagen sponge made from porcine dermal collagen. Using this prosthesis, we
      performed cervical tracheal reconstructions on 11 dogs. Three dogs died within 3
      months of reconstruction. Their causes of death were anesthetic accident,
      diarrhea, and suffocation, respectively. Bronchoscopically, the inner surface of
      the prosthesis was almost covered with host tissue by 2 months. However, in one
      dog, a relatively large area of the mesh was exposed in the tracheal lumen at 6
      months; a smaller area was exposed in two other dogs. The appearance of the inner
      surface rapidly became lustrous, and central stenosis was not significant, even
      after 12 months. Histologically, an incomplete epithelial lining at 6 months was
      seen on the reconstructed surface and included ciliated columnar, cuboidal, and
      squamous epithelium. These observations have revealed that this prosthesis has
      high biocompatibility and the potential to overcome problems of stenosis of the
      prosthesis lumen. However, because ulceration persists with this prosthesis,
      additional improvement is needed to reduce the incidence of mesh exposure.

PMID- 8573814
TI  - Primary or established liver cells for a hybrid liver? Comparison of metabolic
      features.
AB  - It is currently in discussion whether or not established liver cell lines can be
      used for an extracorporeal liver assist device. Thus, metabolic features of
      primary hepatocytes, immortalized hepatocytes, and hepatoma cells were compared.
      The ability of these cells to process toxic blood of patients with hepatic
      failure was investigated by testing their viability in toxin enriched medium that
      was obtained by toxin separation from patients' blood via a molecular adsorbents
      recirculating system (MARS). In addition, glucose metabolism, urea synthesis,
      P450 dependent verapamil metabolism using high performance liquid chromatography,
      and interleukin-6 induced "acute phase" reaction by sulfodesoxysalicylic acid
      polyacrylamide gel electrophoresis detected changes of albumin synthesis were
      determined in primary hepatocytes and in established liver cells. The viability
      of hepatoma cells after contact with the toxic compounds coming from the
      patients' blood was significantly decreased in comparison to that of immortalized
      hepatocytes and primary hepatocytes. Immortalized hepatocytes and hepatoma cells
      showed a significantly higher consumption of glucose associated with a
      significantly higher lactate synthesis. A basic urea synthesis rate could be
      measured in immortalized hepatocytes and hepatoma cells, but it was significantly
      lower than that of primary cells. P450 with its subenzyme CYP2C was inducible
      only in primary hepatocytes and in immortalized cells, but in the latter the
      enzymatic activity was lower than that of primary cells. The incubation with
      acute phase mediators resulted in a decrease of albumin synthesis in primary
      hepatocytes and in hepatoma cells, but it increased the albumin synthesis in
      immortalized hepatocytes. Summarizing these data, partially beneficial effects
      can be assumed if established cells are used in an extracorporeal liver assist
      device. These might include synthesis of some compounds and basic metabolic
      activities, such as urea synthesis. However, established liver cells showed
      clearly altered metabolic characteristics. The sufficient removal of toxic
      compounds requires additional strategies for detoxification by primary
      hepatocytes in sufficient amounts.

PMID- 8573816
TI  - Obstructive uropathy in gynecologic malignancy. Detrimental effect of
      intraureteral stent placement and value of percutaneous nephrostomy.
AB  - Records of all patients with obstructive uropathy and gynecologic malignancy were
      reviewed to determine treatment, including indications for dialysis, and
      outcomes. Over 5 years (July, 1989-June, 1994), 41 patients were identified, 34
      of whom (83%) had renal failure or insufficiency with a serum creatinine
      concentration > or = 1.5 mg/dl. All of those with renal failure had
      hydronephrosis: bilateral in 28 of 34 patients (82%), and unilateral in the rest
      (18%). There was no consistent approach to management, which appeared unrelated
      to staging of cancer, and included unilateral nephrostomy alone (n = 6),
      bilateral nephrostomy (n = 11), intraureteral stent catheter placement alone (n =
      5), a combination of nephrostomy and intraureteral stent catheter placement (n =
      3), urinary diversion into an ileal conduit (n = 2), or no treatment (n = 7). Of
      seven patients who had stent catheter placement, urosepsis developed in six
      (86%), leading to death in three of seven (43%). Bilateral nephrostomy placement
      was clearly valuable in reversing renal failure (p = 0.002), and superior to
      unilateral nephrostomy (p = 0.125), intraureteral stent catheter placement alone
      (p = 0.75), or a combination of nephrostomy and intraureteral stent catheter
      placement (p = 1.0). Only 2 of 34 patients with renal failure (6%) were dialyzed.
      This experience indicates that: 1) intraureteral stent catheter placement
      predisposes to urosepsis and should be avoided; 2) bilateral nephrostomy
      placement allows significant improvement in renal function, and is superior to
      either unilateral nephrostomy placement or combination nephrostomy-stent catheter
      placement; and 3) dialysis is rarely applied to this population.

PMID- 8573815
TI  - Cryofiltration apheresis for treatment of cryoglobulinemia associated with
      hepatitis C.
AB  - Cryofiltration apheresis (CA) is a specific therapy for treatment of patients
      with cryoglobulinemia. We evaluated the safety and efficacy of CA in patients
      with mixed cryoglobulinemia associated with hepatitis C. As reported previously,
      the Cryoglobulin Filter comprises a membrane module inside a refrigeration unit
      on-line with a Spectra Apheresis System (COBE, Denver, CO). The efficacy of
      cryofiltration was measured by comparing the sieving coefficient of
      cryoprecipitable proteins (CPP) to that of albumin and comparing the systemic CPP
      concentration ratio post to pre treatment. Five patients were enrolled in this
      study, and a minimum of 10 procedures were performed for each patient. The risk
      for hepatitis C was multiple blood transfusions, intravenous drug abuse,
      immunosuppressive therapy, or renal transplantation. Four patients had Type II
      mixed cryoglobulinemia, and one patient had Type III. Four patients had chronic
      renal failure; one with liver cirrhosis received alpha interferon along with CA.
      One patient had no response to conventional plasma exchange and immunosuppressive
      therapy secondary to repeated infections and sepsis; CA was the only viable
      therapy for this patient. The maximum CPP concentration before therapy ranged
      from 1,440 to 7,440 micrograms/ml. The plasma CPP sieving coefficient at 1 L
      filtrate ranged from 0.25 to 0.74 (average +/- SE, 0.51 +/- 0.19; n = 39). The
      sieving coefficient for albumin was 1 (n = 50). The systemic CPP ratio post to
      pre treatment ranged from 0.28 to 0.83 (average +/- SE, 0.59 +/- 0.20; n = 37).
      No adverse effects specific to CA were observed. The CA was safe and effective
      and possibly the only choice of therapy in patients with cryoglobulinemic
      hepatitis C who have no response to plasma exchange and immunosuppressive
      therapy.

PMID- 8573817
TI  - Development and in vivo evaluation of an implantable left ventricular assist
      system with an impedance based monitoring and control system.
AB  - We have developed an implantable pneumatically driven diaphragm left ventricular
      assist system (LVAS) for small adults, and an electric impedance based monitoring
      and control system (Z system). In this Z system, measurement of electric
      impedance of the blood chamber is performed by charging an alternating current
      with a constant amplitude between two metal connectors without compromising anti
      thrombogenicity. Automatic calibration was performed periodically by measuring
      trough values of impedance in the blood chamber for several beats while the blood
      pump was in a full-fill state under preset driving conditions. For precise
      control of the fill-to-empty (F/E) drive, an automatic trigger level adjustment
      method was developed. This method is an automatic searching algorithm that
      identifies the volume change of the last ejection or filling by the Z system and
      settles the next trigger level to maintain a definite stroke volume. In chronic
      in vivo evaluation, this LVAS was used in 13 adult goats. The pump was installed
      between the LV apex and the descending aorta and was placed in the abdominal
      wall. Pump output ranged from 2.5 to 5.8 L/min, and the Z system provided good
      monitoring. The F/E drive was achieved satisfactorily by this Z system. The
      physical condition of the goats was excellent for as long as 19 weeks.
      Hematologic, hepatic, and renal functions were within the normal range, and no
      prominent thromboembolic symptoms were observed. A new mobile control drive unit
      with this Z system is being developed. We conclude that this LVAS with the Z
      system is promising for long-term use in a clinical setting.

PMID- 8573818
TI  - An intraventricular axial flow blood pump integrated with a bearing purge system.
AB  - The future development of implantable axial flow blood pumps must address two
      major issues: mechanically induced hemolysis and shaft seal reliability. The
      recent revisions to our miniature intraventricular axial flow left ventricular
      assist device (LVAD) were aimed particularly at addressing these concerns. To
      improve hemocompatibility, a new impeller has been designed according to the
      following criteria: 1) gradual pressure rise along the blade chord; 2) minimized
      local fluid acceleration to prevent cavitation; 3) minimum surface roughness; and
      4) radius edges. Subsequent in vitro hemolysis tests conducted with bovine and
      ovine blood have demonstrated very low hemolysis (normalized index of hemolysis =
      0.0051 +/- 0.0047 g/100 L) with this new impeller design. To address the need for
      a reliable seal, we have developed a purged seal system consisting of a miniature
      lip seal and ceramic pressure groove journal bearing that also acts as a purge
      pump. Several spiral grooves formed on the bearing surface provide viscous
      pumping of the purge fluid, generating more than 3,000 mmHg at 10,000 rpm. This
      purge flow flushes the lip seal and prevents blood backflow into the bearing. We
      have found this purge pump to offer several advantages because it is simple,
      compact, durable, does not require separate actuation, and offers a wide range of
      flow, depending upon the groove design. In vivo animal tests demonstrated the
      potential of the purged seal system.

PMID- 8573819
TI  - Five month survival in a calf supported with an intraventricular axial flow blood
      pump.
AB  - We are studying in vivo an intraventricular axial flow blood pump (Jarvik 2000)
      designed for long-term left ventricular support. The small (25 cc, 85 g)
      valveless pump has been placed intraventricularly in seven calves; pumps have
      functioned for as long as 5 months. In the four most recent long-term studies
      completed, calves have survived for 70, 120, 155, and 162 days (in that order);
      weight gain has averaged 0.56 kg/day. One study is ongoing at more than 30 days.
      Under resting physiologic conditions in the normal calf, the continuous flow pump
      produces flows of 5-6 L/min with a decreased arterial pulse contour. The device
      has caused no physiologic complications. Calves in the completed studies had mean
      free plasma hemoglobin levels of 11.4, 7.1, 6.5, and 4.3 mg/dl, respectively. We
      have modified the inflow structures of the device, and these results suggest that
      a thrombus free design with no pannus at or around the inlet of the pump can be
      achieved. Histopathologic analyses of the heart and kidneys in studies of as long
      as 5 months show no deleterious effects of this device. These studies demonstrate
      the feasibility of a small implanted intraventricular blood pump for long-term
      use. Future developments for permanent implantation will include implanted
      physiologic control systems, transcutaneous energy transmission systems, and
      implanted batteries.

PMID- 8573820
TI  - Development of an intravenous axial flow pump for temporary right heart assist.
AB  - In clinical settings, quick application systems with easy access for circulatory
      support are desired. For left heart assist, an intraarterial axial flow pump
      (Hemopump) has been developed and applied to clinical cases. However, no simple
      way has been proposed for right heart assist. We have developed an intravenous
      axial flow pump for temporary right heart assist and have reported its
      hemodynamic effect. In this study, in vivo evaluation of this system was
      performed. The pump system consists of an outflow cannula, an impeller that was
      newly developed for intravenous use, and a driving system for the Hemopump. A
      prototype pump demonstrated 3.2 L/min of maximal flow at a pressure differential
      against 40 mmHg at a pump speed of 28,000 rpm in mock circulation. Application to
      goats is as follows. A 14 mm low porosity graft was anastomosed to the infrarenal
      inferior vena cava (IVC). The pump system was inserted into the IVC through the
      graft and advanced to the right heart using balloon catheter guidance under
      fluoroscopy, and the tip of the cannula of the pump was positioned at the main
      pulmonary artery. In acute experiments, this system provided effective right
      heart assist under induced pulmonary stenosis and induced biventricular failure
      with left ventricular assist. Chronic animal experiments were performed for as
      long as 4 hr using adult goats weighing 51-54 kg. There were no difficulties in
      pump insertion. In one goat, the drive shaft was broken because of kinking of the
      shaft inside the body, caused by failure in securing the pump. Levels of platelet
      counts and plasma hemoglobin were acceptable, and there was no prominent damage
      to heart tissues. In conclusion, an intravenous axial flow pump introduced
      through a peripheral vein is practicable for temporary right heart assist.

PMID- 8573821
TI  - A mechanical auxiliary ventricle. Histologic responses to long-term, intermittent
      pumping in calves.
AB  - The mechanical auxiliary ventricle (MAV) is an avalvular, inseries left
      ventricular assist device (LVAD) comprised of a 60 cc Biomer blood pump implanted
      in the descending thoracic aorta, a percutaneous access device (PAD), and an
      external pneumatic drive. In four calves the MAV was implanted and activated
      intermittently for 192, 249, 423, and 785 days, respectively; no anticoagulants
      were administered. When the animals were killed, the implants were retrieved, and
      autopsies, including gross, light microscopic, scanning electron microscopy
      (SEM), and transmission electron microscopy (TEM) examinations, were performed.
      The MAV was securely attached to the aorta in every animal. A thin, even smooth,
      pseudoneointimal layer (PNI) contiguous with the aorta at the level of the suture
      line covered the MAV's blood-contacting surface. Areas of calcification beneath
      the PNI, expected in growing animals with implanted pumping devices, were noted.
      At autopsy there was no evidence of thrombosis or infection in the regions of the
      blood pump or the PAD. These findings confirm the calves' benign histologic
      response to the MAV, and together with the results of hematologic and
      biochemiccal studies, and bench tests of system components being reported
      elsewhere, indicate the system's readiness for limited clinical investigation in
      selected patients with chronic congestive failure.

PMID- 8573822
TI  - A magnetically suspended centrifugal pump. In vitro and in vivo assessment.
AB  - To overcome problems derived from the shaft within conventional centrifugal
      pumps, we have developed a new centrifugal pump, the magnetically suspended
      centrifugal pump (MSCP), which has no shaft and operates as a bearingless
      centrifugal pump. The impeller is suspended freely and centrally by magnetic
      force within the pump. Hemolysis tests were performed in comparison with the
      Biopump. Index of hemolysis and destruction of platelets were significantly lower
      in the MSCP than in the Biopump. Animal studies were designed to evaluate the
      durability and antithrombogenicity of the MSCP. Short-term animal studies were
      performed using two mongrel dogs. Left heart bypass was established with the
      MSCP. After 3 hr, the layer of thrombus adherent to the surface of the
      polycarbonate impeller impaired pumping efficiency. However, using the impeller
      coated with silicone, no thrombus was observed on the impeller after continuous
      pumping for 24 hr. In addition, long-term animal studies were performed using two
      sheep. Left heart bypass was established with the MSCP containing an impeller
      coated with silicone. In one sheep, the MSCP ran for 14 days without problems in
      pumping performance and showed no thrombus within the pump. In the other sheep,
      the MSCP ran for 15 days, and showed no thrombus on the impeller. During each
      experiment, plasma free hemoglobin levels were less than 15 mg/dl. The MSCP
      induced less hemolysis than did the Biopump, and the MSCP containing an impeller
      coated with silicone demonstrated the potential to run for 14 days without
      thrombus formation within the pump.

PMID- 8573823
TI  - Improvement in antithrombogenicity in a centrifugal pump with self wash-out
      structure for long-term use.
AB  - Antithrombogenicity in the initial (NCVC-1) centrifugal pump (CP) developed at
      our institute is provided by a central balancing hole in an impeller that
      promotes self wash-out blood flow (Sf) around the impeller. The current CP (NCVC
      2) was ameliorated to obtain better antithrombogenicity, where the balancing hole
      diameter was widened to improve Sf velocity (Vsf), and the edge of a thrust
      bearing (TB) was rounded to minimize flow separation. Effects of the
      modifications were assessed in in vitro and in vivo studies. The Vsf of the NCVC
      1 and the NCVC-2 evaluated by Doppler velocimeter were 12.8 and 22.1 cm/sec,
      respectively. Flow around the TB visualized by a light cutting method confirmed
      less flow stagnation in the NCVC-2. In vivo antithrombogenicity of the CPs was
      investigated in three goats. A pulsatile VAD (P-VAD) was installed
      paracorporeally between the left atrium and the aorta. After 3 weeks, the P-VAD
      was exchanged for the NCVC-2 and the NCVC-1 in sequence. Each CP was driven for 1
      week and disassembled. No anticoagulation was used, except for heparin injection
      at pump exchange. Thrombus at the TB was found in the two NCVC-1s, and two little
      thrombi were on the impeller of another NCVC-1, whereas a thrombus smaller than 1
      mm3 at the TB was noted in one NCVC-2. These results indicate that the NCVC-2 has
      better antithrombogenicity and Sf around the impeller and the TB.

PMID- 8573824
TI  - Dielectric spectrogram for instantaneous evaluation of ischemic injury of the
      liver.
AB  - Electrical properties of tissues sensitively reflect structural and physiologic
      changes. The authors examined the use of a dielectric spectrogram for
      instantaneous evaluation of ischemic injury of the liver. Wistar rats, which had
      enough collateral circulation for portal bypass with subcutaneous transposition
      of the spleen, were used. Four ischemic periods (15, 30, 60, and 120 min) were
      examined and followed by reflow. Permittivity and conductivity were measured at
      39 frequency points in the 20 Hz-1 MHz range using an LCR meter system. They were
      then expressed in a loss tangent (LT) plot to clear their behavior. The maximum
      LT value (max-LT) and the minimum LT value (min-LT) of the normal liver were 3.98
      +/- 0.28 and 2.98 +/- 0.22, and appeared in 15-20 kHz and 150-300 kHz,
      respectively. During the first 30 min after ischemia, max-LT decreased to 3.25 +/
      0.14 (p < 0.005) and its range shifted to 0.3-0.6 kHz, and min-LT decreased to
      1.35 +/- 0.06 (p < 0.001) without shifting of range. Max-LT then decreased
      gradually and min-LT began to increase. After reflow, max-LT increased and higher
      max-LT was observed in the longer ischemic cases. Max-LT at 1 hr after reflow
      correlated negatively with recovery rate of bile flow at that time (y = -0.238x +
      1.84, r2 = 0.82). Additionally, the difference between max-LT and min-LT at just
      before reflow (dif-LT) showed a significant correlation coefficient with recovery
      rate of bile flow at 1 hr after reflow (y = 2.22x -3.32, r2 = 0.92).

PMID- 8573825
TI  - In vitro characterization of a magnetically suspended continuous flow ventricular
      assist device.
AB  - A magnetically suspended continuous flow ventricular assist device using magnetic
      bearings was developed aiming at an implantable ventricular assist device. The
      main advantage of this device includes no mechanical wear and minimal chance of
      blood trauma such, as thrombosis and hemolysis, because there is no mechanical
      contact between the stationary and rotating parts. The total system consists of
      two subsystems: the centrifugal pump and the magnetic bearing. The centrifugal
      pump is comprised of a 4 vane logarithmic spiral radial flow impeller and a
      brushless DC motor with slotless stator, driven by the back emf commutation
      scheme. Two radial and one thrust magnetic bearing that dynamically controls the
      position of the rotor in a radial and axial direction, respectively, contains
      magnetic coils, the rotor's position sensors, and feedback electronic control
      system. The magnetic bearing system was able to successfully suspend a 365.5g
      rotating part in space and sustain it for up to 5000 rpm of rotation. Average
      force-current square factor of the magnetic bearing was measured as 0.48 and 0.44
      (kg-f/Amp2) for radial and thrust bearing, respectively. The integrated system
      demonstrated adequate performance in mock circulation tests by providing a 6
      L/min flow rate against 100 mmHg differential pressure at 2300 rpm. Based on
      these in vitro performance test results, long-term clinical application of the
      magnetically suspended continuous flow ventricular assist device is very
      promising after system optimization with a hybrid system using both active
      (electromagnet) and passive (permanent magnets) magnet bearings.

PMID- 8573826
TI  - Inhibition of bacterial adhesion and biofilm formation by a heparinized
      hydrophilic polymer.
AB  - The adhesion and growth of two pathogenic bacteria (Escherichia coli and
      Staphylococcus aureus) on the surface of a heparinized hydrophilic polymer were
      studied. Heparinized hydrophilic polymer is composed of poly(vinyl chloride)
      grafted with poly(ethylene glycol) monomethacrylate, diethylaminoethyl
      methacrylate, and ionically bound heparin. Poly(vinyl chloride) was used as a
      control. Plasma protein pre coated polymers were also prepared to evaluate the
      effect of proteins on bacterial adhesion. Polymer films were stored in bacterial
      suspensions under gentle shaking at 37 degrees C for 24 hr. The amount of
      adherent bacterial cells was measured by the bioluminescent assay of bacterial
      adenosine triphosphate. Their structure was observed by use of a scanning
      electron microscope. These evaluations demonstrated that a large amount of
      bacterial adhesion and biofilm formation was found on the surface of poly(vinyl
      chloride), whereas significant reductions in bacterial adhesion and no biofilm
      formation were observed on heparinized hydrophilic polymer. Bacterial adhesion
      onto plasma protein pre coat polymer films were also investigated, and it was
      clear that the bacterial adhesion on these surfaces was dependent upon the amount
      and species of absorbed proteins.

PMID- 8573827
TI  - In vivo and ex vivo evaluation of the antithrombogenicity of human thrombomodulin
      immobilized biomaterials.
AB  - Human thrombomodulin (hTM) is a newly described endothelial cell associated
      protein that functions as a potent natural anticoagulant by converting thrombin
      from a procoagulant protease to an anticoagulant. Focusing on the establishment
      of the practical evaluation of hTM immobilized materials, the activity of
      immobilized hTM was evaluated by in vivo and ex vivo blood contacting tests. As
      the basis for immobilization, regenerated cellulose films and hollow fibers were
      used. For the in vivo test, hTM immobilized cellular hollow fibers were implanted
      into dog blood vessels. Using hTM immobilized cellulose hollow fibers, a small
      scale dialyzer was assembled and its antithrombogenic activity was studied using
      human blood. As a result, it was revealed that the immobilized hTM still has co
      enzymatic activity for activation of Protein C and anticoagulant activity. The
      coagulation time of the human blood passed through the hTM immobilized small
      dialyzer was effectively prolonged. It is expected that hTM immobilized cellulose
      should be a useful antithrombogenic biomaterial.

PMID- 8573828
TI  - Newly designed hemostatic technology based on photocurable gelatin.
AB  - In this article, the authors present a novel photochemically driven hemostatic
      technology using photocurable gelatins partially derivatized with photoreactive
      xanthene dyes (fluorescein, eosin, and rose bengal) and a hydrophilic
      difunctional macromer. The developed hemostatic glue consisted of dye derivatized
      gelatin (20 wt%), poly(ethylene glycol) diacrylate (10 wt%), and ascorbid acid
      (0.3 wt%), all of which were dissolved in a saline solution. Irradiation of the
      hemostatic glue by visible light produced a swollen gel within a few tenths of a
      second due to dye sensitized photo-crosslinking and photograft polymerization. An
      increase in irradiation time resulted in an increased gel yield and reduced water
      swellability. A rat liver injured on laparotomy was coated with the hemostatic
      glue. Upon visible light irradiation through an optical fiber, the coated viscous
      solution was immediately converted to a swollen gel and, concomitantly,
      hemostasis was completed. Histologic examination showed that, at 7 days after
      surgery, little gelatin remained in the injured region, scarring with little
      necrosis occurred, and inflammatory cells infiltrated from the surrounding tissue
      and tissue regeneration proceeded well. During laparoscopic surgery, in situ
      gelation of the hemostatic glue on the liver surface was demonstrated using a
      specially designed fiberscope.

PMID- 8573829
TI  - Synthesis of aromatic polyimides with sulfone diamine moieties for a novel
      membrane oxygenator.
AB  - The authors have synthesized soluble aromatic polyimides derived from 2,2'
      bis(3,4-dicarboxyphenyl) hexafluoropropane dianhydride (6FDA) and 3,3'- or 4,4'
      diamino-diphenylsulfone (m-DDS or p-DDS) to develop a novel membrane oxygenator.
      Asymmetric gas exchange membranes for the oxygenator were prepared by a dry/wet
      phase inversion process. The resulting membrane structure consisted of an
      ultrathin, selective, and defect free skin layer supported by a porous
      substructure. The membranes exhibited extremely high gas flux and selectivity.
      CO2 flux through the polyimide membranes used in this study increased with a
      decrease in CO2 pressure and was in accordance with the dual mode transport
      described by a combination of the Henry and Langmuir modes. This indicates that
      CO2 is selectively removed from the membranes at low CO2 pressure as compared
      with presently available materials for membrane oxygenators, such as
      polydimethylsiloxane and polypropylene. The number of platelets adherent to the
      surface of the polyimide were significantly smaller than those on
      polydimethylsiloxane and polypropylene, and the deformation and aggregation of
      platelets on polyimide were not observed. These findings suggest that aromatic
      polyimides with sulfone diamine moieties are promising membrane materials for an
      oxygenator.

PMID- 8573830
TI  - Effect of shear stress on fibrinogen adsorption and its conformational change.
AB  - The composition and molecular organization of adsorbed protein films are strongly
      correlated with thrombogenesis on artificial surfaces. In particular, the
      antibody-detectable (that is, conformationally intact) bound fibrinogen, but not
      that the total amount of adsorbed fibrinogen, is correlated with platelet
      reactivity. In this work, the authors quantified the adsorbed plasma protein
      distribution inside the left ventricular assist device. They also evaluated the
      effect of wall shear stress on protein adsorption and conformational change of
      adsorbed fibrinogen. Conformational change of adsorbed fibrinogen was measured by
      exposing the fibrinogen preadsorbed polyurethane to three anti-fibrinogen
      monoclonal antibodies; the 134B-29 detectable alpha 566-580 domain of fibrinogen
      was increased with increasing concentration of adsorbed fibrinogen, whereas the
      other two fibrinogen domains were almost saturated when increasing the
      concentration of adsorbed fibrinogen. The adsorbed amounts of total fibrinogen
      and monoclonal antibody detectable fibrinogen was decreased with increasing shear
      rate. Results of in vivo plasma protein adsorption on polyurethane surfaces
      disclosed that the adsorbed amount of fibrinogen, as well as albumin and
      globulin, was also decreased with increasing shear rate. In conclusion, less
      protein was adsorbed in the higher shear region and the effect of shear level on
      fibrinogen adsorption and its conformational change was strongly dependent upon
      the surface characteristics of the biomaterials. The monoclonal antibody 134B-29
      against the 566-580 domain of fibrinogen was the most reactive with the
      fibrinogen adsorbed on polyurethane surfaces in this experiment.

PMID- 8573831
TI  - In vitro studies of immobilized heparin and sulfonated polyurethane using
      epifluorescent video microscopy.
AB  - In situ surface modification techniques to improve the blood compatibility of
      blood contacting surfaces of medical devices have been developed by the authors.
      The techniques include heparin immobilization and sulfonated polymer grafting
      onto a polyurethane (PU) surface by using either ozone oxidation or photo
      reaction. These modified PUs were evaluated using an epifluorescent video
      microscope combined with a parallel plate flow cell. The epifluorescent video
      microscope system measured the amount of platelet coverage on the PU surfaces
      using whole human blood containing mepacrine labeled platelets perfused at a wall
      shear rate of 100 sec-1 for 20 min. Platelet activation and complement activation
      were also measured. Both immobilized heparin and sulfonated PUs showed
      significantly lower levels of platelet adhesion than the control PU. The platelet
      activation levels of these modified PUs also correspond to the results of the
      platelet adhesion. As for complement activation, heparin the immobilized surface
      showed the least complement activation, while sulfonated PU and the control PU
      showed higher levels of complement activation. In situ surface modification
      techniques, which use either ozone oxidation or photo reaction, are useful in a
      variety of medical devices even of a complex design, such as membrane oxygenators
      or artificial hearts.

PMID- 8573832
TI  - Inhibition of surface-induced platelet activation by nitric oxide.
AB  - This study was undertaken to determine whether the nitric oxide/platelet cyclic
      guanosine monophosphate (NO/cGMP) pathway might be used to reduce platelet
      activation by artificial surfaces. Because serotonin release (SR) is a platelet
      activation indicator, rabbit platelets in their own plasma (PRP) were labeled
      with 3H-serotonin. Labeled PRP was incubated with glass beads for 5-10 min, at 37
      degrees C with gentle agitation, and SR was measured. PRP pretreatment with NO
      gas or nitroprusside + N-acetylcysteine inhibited SR 50%. Dose response studies
      indicate the existence of an optimal NO concentration above which its inhibitory
      effect is diminished. The guanylate cyclase inhibitor methylene blue attenuates
      the NO effect, implicating cGMP in NO mediated inhibition of surface induced
      platelet activation. Adult pigs were supported on a membrane oxygenator in an in
      vitro model of cardiopulmonary bypass (CPB). Introduction of NO gas into the
      oxygenator sweep gas at 500 ppm reduced platelet adherence to the oxygenator
      surfaces, increased circulating platelet counts, and decreased the rate of
      platelet aggregation (whole blood impedance platelet aggregometry) compared with
      the results of the control animals. Indications of NO toxicity were seen when the
      NO flow rate was increased to 1,000 ppm. These studies support the hypothesis
      that NO reduces platelet activation by artificial surfaces in clinical devices.

PMID- 8573833
TI  - mRNA expression induced by cell-substrate interaction. A two-dimensional tissue
      formation process.
AB  - This study aimed to develop a quantitative assay method of determining cellular
      events at the mRNA level during tissue formation. Quantitative assessment of
      mRNAs coding specific proteins (beta-actin, fibronectin, laminin) during tissue
      formation on tissue culture dishes was attained using a Northern blot technique
      with autoradiography. The amount of beta-actin mRNA, the expression of which is
      initiated shortly after adhesion, greatly increased with incubation time and
      reached maximal levels near the confluent state, followed by a reduced expression
      at a later stage of tissue formation. The time course of beta-actin mRNA
      expression, which reflects cytoskeletal organization, corresponded well to
      morphologic changes in adherent cells. Expression of mRNAs coding the
      extracellular matrix proteins, fibronectin and laminin, was initiated at the
      proliferation stage. After maximum expression levels were observed at the
      confluent stage, a gradual decrease in the expression of both mRNAs was seen
      after longer culture periods. Expression patterns of mRNAs coding cytoskeletal
      and extracellular matrix proteins greatly depended upon the type of artificial
      substrates. Thus, the dynamic changes in tissue formation were quantified to
      elucidate the significance of artificial substrates in tissue formation at the
      mRNA level.

PMID- 8573834
TI  - A micro carbon electrode for nitric oxide monitoring.
AB  - A nitric oxide (NO) probe, consisting of a micro carbon fiber working electrode,
      10 microns diameter, a platinum counter electrode, and a silver/silver chloride
      (Ag/AgCl) reference electrode, has been developed. The carbon fiber working
      electrode is covered with a Nafion cation exchange membrane. Using differential
      pulse voltammetry (DPV), we found the NO to N2O reduction current peak at
      approximately -1.35 V versus Ag/AgCl. This has been reported by others. The DPV
      current outputs are linearly related to dissolved NO concentrations [NO] in the 2
      10 microM range. Catecholamines were found not to interfere with the reduction
      signal. The Nafion membrane also prevents interference by NO2-, NO3-, and amino
      acids at normal physiologic pH (pH 7.4). The effects of O2 are accounted for
      through sampling and subtracting background currents from the peak current. To
      increase sensitivity and shorten response time, a method of integrated pulse
      amperometry (IPA) was used for the study. The IPA charge outputs (delta C) are
      linear to the dissolved [NO] in the 50-350 nM range. The carbon fiber electrode
      has the potential of being miniaturized to a smaller electrode, allowing
      detection of NO released from the subendothelial space.

PMID- 8573835
TI  - A microchip glucose sensor.
AB  - A major problem in development of a glucose sensor for use in an implantable
      artificial pancreas is the lack of reproducibility in signals from sensor to
      sensor. Each glucose sensor fabricated with currently used methods has a unique
      response to varying levels of glucose concentration and thus needs to be
      individually calibrated before use. We have adapted microchip manufacturing
      techniques for the fabrication of electrochemically based glucose sensors with
      standardized and reproducible function. Scanning electron microscopic study of
      the resulting electrode surfaces shows them to be smooth and featureless at all
      levels of magnification. X-ray diffraction analysis of the electrodes indicates
      preferential exposure of the [1,1,1] crystal interface. Cyclic voltammetry
      evaluation of initial sensor response to varying glucose concentrations shows
      excellent sensor to sensor reproducibility for all sensors made with the same
      underlayment. Sensors made with titanium underlayment appear to be more
      differentiated and thus more sensitive to variations in glucose concentration
      than are sensors with chromium underlayment. Although the initial response of
      microchip glucose sensors appears to be standardized and reproducible, additional
      development of an appropriate electrical insulation material is required before
      long-term study of signal stability is feasible.

PMID- 8573836
TI  - A nitric oxide sensor using reduction current.
AB  - Nitric oxide (NO) has a wide range of biologic activity. Methods commonly used
      for the detection of biologically derived NO are indirect and measure only the
      amount of NO released during an interval of time. An electrochemical method
      available is capable of being direct and continuous but is subject to
      interference. The recent explosion of scientific research into NO activity
      requires better methods of NO detection. This article reports a new NO
      electrochemical sensing method and sensor design. The tip of the sensor is
      covered with a hydrophobic membrane and contains an internal electrolyte.
      Platinum is used for the working and counter electrodes and silver/silver bromide
      (Ag/AgBr) for the reference electrode. The components of the internal electrolyte
      are potassium bromide and sulfuric acid. The NO that diffuses to the working
      electrode is first oxidized to NO+; the NO+ is reduced to NO; and the reduction
      current is determined. An integrated pulsed amperometric method is used to
      achieve the redox of NO and the measurement and integration of the reduction
      current. The results show that the NO sensor is sensitive and has a rapid
      response and less interference.

PMID- 8573837
TI  - Design and properties of photocurable electroconductive polymers for use in
      biosensors.
AB  - The authors report preparation of a new hydrophilic photocurable
      electroconductive polymer to be used as a matrix for an enzyme based biosensor.
      Polymers, prepared by radical terpolymerization, consisted of N,N
      dimethylacrylamide (DMAA) as the water soluble part, m-azidostyrene (AzSt) as the
      photochemically active center to entrap an enzyme and to fix it on an electrode,
      and vinylferrocene (VFe) as the charge transfer mediator between an enzyme and an
      electrode. Ultraviolet light (UV) irradiation to the terpolymer coated on a
      carbon electrode produced a water swellable cross-linked polymer that was
      chemically fixed on a carbon electrode. Cyclic voltammetry on a hydrogelated
      electrode in a phosphate buffered solution exhibited single oxidation/reduction
      reproducibly, indicating that the formed conducting hydrogel was stable. An
      increase in VFe content and a decrease in AzSt content of a terpolymer resulted
      in larger electrochemical responses on normal pulse voltammetry. When glucose
      oxidase was immobilized in a hydrogel, a dose dependent electrochemical response
      to glucose was observed.

PMID- 8573838
TI  - An analysis of the adequacy of preparation for end-stage renal disease care in
      Michigan. Michigan Renal Plan Task Force.
AB  - The Michigan Renal Plan Task Force has been charged with the development of a
      comprehensive plan to optimize the management of renal disease in Michigan. To
      assess the preparedness of new patients with end-stage renal disease (ESRD)
      patients in Michigan, surveys were sent to all outpatient ESRD facilities in the
      state concerning all new ESRD outpatients starting treatment during the first
      quarter of 1994. Responses were received from 69% of these facilities, covering
      439 patients; 73% of patients were admitted to the hospital at the initiation of
      dialysis, and 69% required a temporary dialysis catheter. The median time to
      first outpatient dialysis was 10 days. Hospital admittance and use of temporary
      catheters were associated with a lower serum albumin at 1 month of follow-up.
      Temporary dialysis catheter usage was highest (85%) in rural areas, and lowest
      (59%) in suburban centers. Fifty-four percent of patients had a 1 month serum
      albumin of < or = 3.5 g/dl. At 1 month, nearly 60% of patients had a plasma
      hemoglobin of < or = 10.0 g/dl. These results suggest that better patient
      preparation for ESRD is needed to reduce the need for hospital admittance, to
      reduce the use of temporary catheters with their associated risks, and to improve
      the nutritional and psychosocial rehabilitation of these patients.

PMID- 8573839
TI  - Resurgence of blood transfusion therapy in erythropoietin treated hemodialysis
      patients.
AB  - Anemia, a major component of the uremia syndrome before the introduction of
      recombinant human erythropoietin (EPO), was treated primarily with blood
      transfusions in patients with end-stage renal disease (ESRD). After multi-center
      trials of EPO in hemodialysis patients showed that blood transfusion requirements
      fell by > or = 50% in hemodialysis facilities using EPO, it was anticipated that
      blood transfusion therapy in hemodialysis patients would be eliminated in
      patients treated with EPO. The authors examined the annual rate of blood
      transfusions from 1983 to 1992 in hemodialysis patients admitted to an inner city
      municipal hospital. Hospital computer records were accessed to obtain a list of
      all patients admitted to the hospital who received a blood transfusion between
      1983 and 1992. From these data, lists of transfused hemodialysis patients were
      generated. The authors compared the mean annual blood transfusion rate per
      hospital patient in the pre EPO era (1983-1985) with the same rate during the
      time of EPO trial (1986-1988) and during the time of wide clinical availability
      of EPO (1989-1992). In addition, the authors examined individual hospital medical
      records of hemodialysis patients who received transfusions in 1986 and 1992. The
      mean annual blood transfusion rate was 38% (range, 36-39%) in the pre EPO era,
      19% (range, 16-24%) during the years of the EPO trial, and 23% (range, 21-24%)
      after EPO was widely used in 1989, comparing the latest rate with either of the
      two earlier times (p < 0.0001). Of all of the years tabulated, the blood
      transfusion rate was lowest in 1987, the second year of the EPO clinical trial,
      with only 94 (16%) of 592 hemodialyzed patients given a blood transfusion. The
      rate of blood transfusions remained low in 1988 (18%) but subsequently has
      increased. Using 1987 as a reference point, the rate of blood transfusion in
      hemodialysis patients increased in each of the subsequent years after 1988 (18%,
      p < 0.33); 1989 (23%, p < 0.001), 1990 (24%, p < 0.0001), 1991 (21%, p < 0.02),
      and 1992 (23%, p < 0.0001). The authors conclude that, despite the availability
      and broad use of EPO in uremia therapy since 1989, a significant proportion of
      hemodialysis patients receiving EPO treatment require blood transfusions for
      anemia.

PMID- 8573840
TI  - Development of cationically modified cellulose adsorbents for the removal of
      endotoxins.
AB  - The removal of endotoxins by extracorporeal adsorption processes seems the most
      promising therapeutic approach to Gram-negative sepsis and endotoxin shock.
      However, thus far adsorbents have failed to bind endotoxins efficiently or have
      shown adverse biocompatibility characteristics. To overcome these disadvantages,
      small particles of regenerated cellulose in the range of 1-8 microns in diameter
      were produced. Before use, the microspheres were cationically modified by
      substitution with polyethyleneimine (PEI) or diethylaminoethyl (DEAE) groups. A
      third kind of adsorbent was manufactured by (physically) coating the cellulose
      matrix with PEI. All three types of adsorbents exhibited a high adsorption
      capacity for endotoxins in human plasma, whereas activated charcoal and various
      anion exchange resins removed only small amounts of endotoxins under the same
      conditions. In addition, because the outer surface area is very large, adsorption
      takes place rapidly and diffusion becomes almost irrelevant. The adsorption
      process is primarily based on electrostatic interactions, which could be
      demonstrated by a significantly higher adsorption rate and binding capacity for
      lipid A-diphosphoryl, compared with lipid A-monophosphoryl. Use of these
      adsorbents in a newly developed plasma sorption system could be of great clinical
      interest because of the low production costs, the high adsorption efficiency, and
      the excellent biocompatibility data.

PMID- 8573841
TI  - Sleep apnea in end-stage renal disease patients on hemodialysis and continuous
      ambulatory peritoneal dialysis.
AB  - Fifteen unselected end-stage renal disease patients (nine hemodialysis [HD] and
      six continuous ambulatory peritoneal dialysis [CAPD]) were randomly selected from
      four Sydney metropolitan dialysis centers for sleep assessment by full
      polysomnography. Four of six CAPD patients and eight of nine HD patients were
      found to have clinically significant obstructive sleep apnea. An additional 21
      unselected patients (10 CAPD and 11 HD patients) were assessed using overnight
      home monitoring of nasal airflow and arterial oxygen saturation. Of these, 8 of
      the 11 HD and 7 of the 10 CAPD patients were found to have obstructive sleep
      apnea. These data confirm the high incidence of obstructive sleep apnea in the
      end-stage renal disease population at large. Screening for obstructive sleep
      apnea should become a routine part of the management of these patients.

PMID- 8573842
TI  - Lean body mass estimation by creatinine kinetics, bioimpedance, and dual energy x
      ray absorptiometry in patients on continuous ambulatory peritoneal dialysis.
AB  - Lean body mass (LBM), which is fat free body mass, can be used as an index of
      nutritional status. We evaluated three techniques for LBM estimation, including
      dual energy x-ray absorptiometry (DEXA), creatinine kinetics (CrKin), and
      bioimpedance (BI) in 10 patients on continuous ambulatory peritoneal dialysis
      (CAPD). Two different formulae were applied for BI LBM estimation, Segal (S) and
      Deurenberg (D). Mean values (+/- SEM) of LBM estimated were 48.2 +/- 3.6, 46.12
      +/- 2.87, 43.32 +/- 3.87, and 41.27 +/- 4.26 by DEXA, BI-S, BI-D, and CrKin,
      respectively. LBM by CrKin was significantly lower than that by DEXA and BI-S
      values. There was no statistically significant difference between DEXA and BI-S
      values. Statistically significant correlations were found between LBM values by
      all methods. Particularly strong correlations were found between DEXA versus BI-S
      (r = 0.976) and BI-S versus BI-D (r = 0.98). Because clinical assessment of
      hydration status is inaccurate, and both BI and DEXA measure excess extracellular
      water in LBM, falling muscle mass may be missed by these techniques. The CrKin
      technique for estimating LBM at normal body fluid volumes (dry weight) may be a
      better index of nutritional status in patients on CAPD because this may truly
      reflect the dry LBM and changes in muscle mass. Both DEXA and BI include excess
      body water in LBM and may mask malnutrition in the presence of subclinical or
      clinical overhydration, which is common in patients on peritoneal dialysis.

PMID- 8573843
TI  - A new approach to optimizing urea clearances in hemodialysis and continuous
      ambulatory peritoneal dialysis.
AB  - Recent studies suggest that the relationship of the net normalized protein
      catabolic rate (which is the normalized protein equivalent of nitrogen appearance
      [nPNA]) to the weekly clearance of urea normalized to total body water (Kt/V
      urea) in patients on continuous ambulatory peritoneal dialysis (CAPD) is
      curvilinear, rather than linear, as has been thought. The authors have reexamined
      the relationship of nPNA to weekly Kt/V urea in a CAPD population by cross
      sectional analysis to see if the curvilinear definition of the relationship is as
      good as or better than the usual linear description. They also examined this
      relationship in the hemodialysis populations at the Dialysis Clinics Inc. in
      Columbia, Missouri, and in the Renal Kidney Disease Program in Minneapolis,
      Minnesota. It seems obvious that there should be a plateau of nPNA in each
      therapy because extension of linear regressions would predict protein intakes of
      normal individuals exceeding 8 g/kg/body weight/day. The authors compared their
      findings to other published results. Intuitively and analytically, the
      curvilinear relationships seem likely. The authors observed that the nPNA plateau
      is achieved at lower Kt/V in patients on CAPD than in those on hemodialysis,
      which is compatible with the peak concentration hypothesis. Asymptotes for CAPD
      and hemodialysis are similar. Weekly Kt/V urea requirements to achieve nPNA
      values at 95% of the asymptote are greater than those usually delivered. However,
      such nearly complete elimination of uremic appetite suppression may not be
      practical or necessary for achieving acceptable nutritional status and long-term
      survival in most patients. Optimum therapy may be well above adequate therapy
      relative to minimizing appetite suppression by uremia.

PMID- 8573844
TI  - A prospective study of the effect of noncompliance on small solute removal in
      continuous ambulatory peritoneal dialysis. Preliminary report.
AB  - In nine patients on continuous ambulatory peritoneal dialysis (CAPD) who were in
      stable condition, the authors measured the effects of an extra daily exchange on
      small solute removals and clearances and the measured/predicted creatinine
      production (M/P). The goal was to evaluate the sensitivity of M/P to single
      exchange noncompliance. Daily collections of urine and dialysate were performed
      on the usual prescribed program and on the next day with an extra exchange of
      usual exchange volume. The average increase in drain volume of 26% was associated
      with an average increase in M/P of 6%. The maximum M/P increase was 15%; the
      percentage increase in M/P correlated inversely with renal creatinine clearance.
      Daily total urea clearance normalized to total body water by dialysis and renal
      function increased 12%. Extrapolating these findings suggests that an average
      patient with a baseline M/P near 1.0 and renal creatinine clearance of 5 ml/min
      would require more than 50% drain volume noncompliance to yield a M/P of 1.24 on
      the complaint day. A 50% noncompliance may not yield a M/P greater than 1.0 on
      the first compliant day if baseline M/P is less than 0.94. The authors suggest
      monitoring daily urine and dialysis creatinine output because M/P creatinine is
      relatively insensitive to noncompliance (particularly in patients with residual
      renal function) and because there are questions about the accuracy of predictions
      in patients with renal failure using formulae established in different
      populations. The authors recommend simply monitoring total daily creatinine
      output and establishing patients as their own controls. The authors provide a
      table for the interpretation of changes in creatinine output in conjunction with
      changes in other routinely monitored parameters.

PMID- 8573845
TI  - Mechanisms of red blood cell trauma in assisted circulation. Rheologic
      similarities of red blood cell transformations due to natural aging and
      mechanical stress.
AB  - Clinical experience with circulatory support devices has typically shown
      alteration of patient blood rheology exhibited through increasing blood viscosity
      and decreasing erythrocyte deformability. Our hemorheologic studies have
      additionally shown a remarkable increase in red blood cell (RBC) aggregation in
      the blood of artificial heart patients as compared to healthy donors. These
      hemorheologic changes may be caused by mechanical trauma to RBCs. The authors
      hypothesize that the mechanical trauma process, from a rheologic point of view,
      could be analogous to an "accelerated" RBC aging process. The hypothesis was
      examined through in vivo and in vitro experiments on RBCs, age-separated on the
      basis of density, specifically to identify the rheologic similarities between
      aged and mechanically traumatized RBCs. Older RBCs demonstrated an increased
      mechanical fragility, a decreased deformability, and a increased ability to
      aggregate as compared to younger RBCs. RBCs exposed to mechanical stress
      demonstrated similar alterations in the same rheologic parameters. Our
      experiments have also shown that mechanical stress decreases the negative surface
      charge of RBCs as is known to occur in aged RBCs. Similarities found between the
      processes of RBC mechanical trauma and senescence enhance our understanding of
      mechanisms of subhemolytic trauma incurred in assisted circulation. This may
      improve the design and evaluation of future heart assist devices through
      minimizing shear induced blood trauma.

PMID- 8573846
TI  - Acute phase responses of vasoactive hormones to non pulsatile systemic
      circulation.
AB  - Acute phase responses of vasoactive hormones to the rapid conversion of a
      systemic flow pattern from pulsatile or non pulsatile mode to the reverse were
      assessed in 20 goats weighing 45-69 kg. A total left heart bypass was instituted
      under general anesthesia, with pulsatile and non pulsatile pumps interposed in
      the circuit in parallel, and the systemic flow mode was rapidly and
      bidirectionally converted from the pulsatile mode or non pulsatile mode to the
      reverse. Vasoactive hormone levels and hemodynamics were evaluated before and
      after 5 min of conversion. No significant difference was observed between the
      modes either in blood flow or systemic vascular resistance, while the mean aortic
      pressure was significantly higher in the non pulsatile mode than the pulsatile
      mode (106.7 +/- 2.4 versus 99.9 +/- 3.5 mmHg). Among various vasoactive hormone
      levels evaluated, only norepinephrine showed a significant difference between the
      modes, where concentration in the non pulsatile mode was significantly higher
      than the pulsatile mode (391.0 +/- 60.7 versus 309.4 +/- 42.5 pg/ml). No
      correlation was found between the absolute values of mean aortic pressure and
      norepinephrine level, whereas a significant reciprocal correlation was detected
      between the magnitude of inter-mode differences in these two parameters. In
      conclusion, a non pulsatile systemic circulation does not exert significant
      influence on vasoactive hormone levels, except for slight increase in
      norepinephrine with a reciprocally correlated increase in mean aortic pressure.
      It is deduced that activity of the sympathetic nervous system represented by
      norepinephrine level is higher in the non pulsatile mode than the pulsatile mode,
      and the baroreceptor reflex functions in an acute phase after flow mode
      conversion.

PMID- 8573847
TI  - How does the sympathetic nervous system behave during non pulsatile circulation?
AB  - Non pulsatile circulation is commonly applied to clinical cardiopulmonary bypass
      or circulatory assist. However, influences of non pulsatile circulation on
      sympathetic nerve activity, which plays an important role in circulatory control,
      have not been elucidated. In this study the renal sympathetic nerve activity
      (RSNA) was recorded for the first time in goats, whose heart rate and size are
      similar to humans', and the difference during pulsatile and non pulsatile
      circulation was evaluated. Total left heart bypass was instituted in eight adult
      goats under general anesthesia. A pneumatic pulsatile pump and a centrifugal non
      pulsatile pump were incorporated in parallel so that pulsatile circulation and
      non pulsatile circulation could be instantly converted to the other. The pumping
      rate was set at 90/min regardless of the native heart rate during pulsatile
      circulation and the mean aortic pressure was maintained constant at the
      conversion of circulatory mode. The original signals of RSNA were integrated and
      defined as the mean RSNA. The mean RSNA and the mean aortic pressure were
      averaged every 30 sec and quantified during pulsatile circulation and non
      pulsatile circulation. The pulse synchronized burst of RSNA during pulsatile
      circulation immediately disappeared and the mean RSNA significantly increased up
      to 120% of pre depulsation level after changing the circulatory mode to non
      pulsatile circulation. Reverse conversion of circulatory mode from non pulsatile
      circulation to pulsatile circulation decreased the mean RSNA to 79%. The results
      suggest that vasotonus may be affected in its periodicity as well as its quantity
      by the loss of pulsation during the initial phase after depulsation.

PMID- 8573848
TI  - Circulatory assist techniques after cardiomyoplasty. Determinants for clinical
      outcome and later consequences.
AB  - Cardiomyoplasty, in spite of recent improvements, remains a high risk operation.
      The early postoperative period is sometimes very critical, even for patients
      selected from preoperative New York Heart Association functional class IV. During
      the surgical period, poor hemodynamics may be responsible for early death, as
      well as influence latissimus dorsi muscle long-term viability. Circulatory
      assist, including pharmacologic support with enoximone, intraaortic balloon
      counterpulsation (IABP), and ventricular assist devices (VAD), may be needed.
      From February, 1993 to September, 1994, 14 clinical dynamic cardiomyoplasty
      procedures were performed using the Medtronic (Minneapolis, MN) system at Hopital
      La Timone, Marseille, France. Eight patients suffered from early and severe
      postoperative heart failure. Enoximone was used in three patients and IABP in
      five patients. Two days after cardiomyoplasty, one of the IABP patients required
      an implantable left VAD (Thermocardio Systems, Woburn, MA) as a bridge to cardiac
      transplantation. Overall hospital mortality was 7%. The authors studied the
      preoperative clinical data and surgical techniques to find specific risk factors
      that could have influenced postoperative events. Another aim of this study was to
      evaluate long-term benefits in these particular patients. Results showed that
      cardiomyoplasty patients may require complex means to overcome postoperative
      hemodynamic failure, but without necessarily poor long-term results. This should
      be an important step in improving future patient selection.

PMID- 8573849
TI  - A single skeletal muscle powered ventricle that assists both systemic and
      pulmonary circulations.
AB  - Extraaortic counterpulsation using skeletal muscle powered ventricles (SMPVs) has
      been studied mainly for the purpose of assisting the systemic circulation. The
      purpose of this study was to investigate the possibility of assisting both the
      systemic and pulmonary circulations using a single SMPV. An SMPV that
      counterpulses the systemic circulation is placed beside the right atrium (RA) or
      the right ventricle (RV), the former after procedures such as a Fontan operation,
      and the latter in cases of biventricular failure. Because the SMPV dilates
      passively during cardiac systole, it is designed to press the RA or the RV
      directly from outside. This study is a preliminary report, and only the ability
      of a specially constructed SMPV to dilate was assessed. Using seven dogs with
      heart failure, the SMPV dilated with an internal pressure of 88 mmHg and 1.0 cm,
      while the volume inside increased by 10.8 ml. From these results, it is suggested
      that the SMPV has enough dilating power to press the RA or to assist the RV while
      counterpulsing the systemic circulation.

PMID- 8573850
TI  - Double chamber ventricular assist device with a roller screw linear actuator
      driven by left and right latissimus dorsi muscles.
AB  - A double chamber ventricular assist device (VAD) with a roller screw linear
      muscle actuator (RSLMA) driven by the left and right latissimus dorsi muscles was
      developed. The inflow port of each chamber was connected to form the compound
      inflow port, and the outflow ports were connected to form the compound outflow
      port. The advantages of this system include 1) the contraction of each muscle
      contributes to ejection from each ventricle into the common outflow port, thus
      doubling the net outflow; 2) through proper adjustment of muscle length, the
      preload to each muscle can be optimized to yield the maximum muscle force; 3)
      muscle can be stimulated at a lower rate to reduce fatigue and to optimize muscle
      performance; and 4) the compliance chamber needed in the implantable VAD system
      is not required with this system. In vitro evaluation in the mock loop with the
      human arm actuating the RSLMA revealed that the double chamber VAD can provide
      pump flows of 2-4 L/min against an afterload of 100 mmHg at a stimulation rate of
      35-50 beats per minute. The power requirement for each muscle ranged from 2.5 to
      3 W at a muscle stroke length of 4 cm. These results verify that the double
      chamber VAD with the RSLMA driven by the left and right latissimus dorsi muscles
      can meet the design requirements of a muscle driven VAD to assist the left heart.

PMID- 8573851
TI  - Mechanical advantage of skeletal muscle as a cardiac assist power source.
AB  - The insertion of unconditioned latissimus dorsi muscle at the humerus was
      reattached in anesthetized goats to the first stage piston of a two stage
      mechanical-to-hydraulic energy convertor for a skeletal muscle powered
      ventricular assist device. To study a range of forces, pistons of different cross
      sectional areas were evaluated during thoracodorsal nerve stimulation. Each
      energy convertor piston was coupled hydraulically to an actuator on a Thoratec
      VAD (Thoratec Laboratories, Berkeley, CA) in a mock circulatory loop. Maximum
      force (70.1 +/- 10.8 N) was greatest for the largest piston, and stroke length
      (4.0 +/- 0.7 cm) was greatest for the smallest piston. However, maximum stroke
      work (1.2 +/- 0.5 J) and muscle powered VAD ejected stroke volume (45 +/- 17 ml)
      were greatest for the middle size piston. These results are consistent with a
      biomechanical model of whole muscle contraction that predicts that there is an
      optimum force that produces maximum cycle work. Thus, with a two stage energy
      convertor, by changing the ratio of the cross sectional areas of the energy
      convertor and muscle powered VAD actuator pistons, the effective mechanical
      advantage for the muscle can be optimized to produce more work output and muscle
      powered VAD flow. Skeletal muscle powered devices using such an energy convertor
      could provide completely implantable circulatory support free from batteries and
      other power conditioning hardware required with electromechanical systems.

PMID- 8573852
TI  - Acute systolic and diastolic indices of left ventricular function after
      cardiomyoplasty in a chronic model of heart failure.
AB  - Recent experimental studies have suggested that the initial nonstimulated stage
      of dynamic cardiomyoplasty acutely impairs ventricular function. Those
      investigations were performed on normal hearts and primarily examined diastolic
      alterations as a result of the passive muscle wrap. The purpose of this study was
      to assess the acute systolic and diastolic effects of a nonstimulated muscle wrap
      in chronic heart failure induced by rapid ventricular pacing in canines. Pressure
      volume analysis of ventricular function based on conductance catheter volume and
      micromanometer pressure data was used. Each animal was studied before rapid
      pacing, before cardiomyoplasty, and immediately after wrap. By the end of the
      pacing period and before wrap, left ventricular dysfunction developed in all
      dogs, manifested by significant deterioration of both systolic and diastolic
      indices of ventricular function, as well as progressive increases in left
      ventricular volumes. However, no further deterioration with load insensitive
      indices of systolic or diastolic indicators of ventricular function was found as
      a result of the passive muscle wrap. These results suggest that the
      cardiomyoplasty procedure can be safely performed on failing hearts without
      prohibitive acute impairment of ventricular function.

PMID- 8573853
TI  - Is it possible to perform immediate cardiac assist using untrained latissimus
      dorsi muscle in a work-rest regimen?
AB  - The authors investigated what contractile force (CF) could be obtained from
      unconditioned latissimus dorsi muscle immediately after mobilization and for the
      2 week vascular period of recovery. Latissimus dorsi muscle mobilization was
      performed on seven adult (4 experimental and 3 control) sheep leaving only the
      pedicle and the peripheral muscle intact. Telectronics stimulators (Myostim 7220;
      Teletronics Pacing Systems, Inc, Englewood, CO) were implanted. Immediately after
      mobilization 11-35% of the initial CF was lost. A 30 min fatigue test was
      performed 1 hr after mobilization (20 g/kg preload, 10 V, 10 Hz, 15 BPM, 6
      impulses per burst) using a 1 min work-1 min rest regimen. Two sheep lost 2-12%
      of initial CF; two increased CF by 14-24%. At the end of the fatigue test, CF
      consisted of 74-89% of immobilized CF. Electrical stimulation training of the
      muscle was then initiated with the following regimen in the experimental animals
      only: 15 BPM, single impulses, 5 V, 10 Hz. Every day the muscle was exercised
      using a work-rest regimen to mimic cardiac assist, starting with 20 min on day 2,
      and increasing by 2 min per day until a total of 50 min was reached on day 16.
      All animals were retested for CF using a 42 min fatigue test on days 6, 11, and
      16. On day 6, there was no fatigue evident in the experimental group during the
      42 min test. CF after testing was 59-81% (mean 67%) of initial data. In the
      control group (animals with no electrical stimulation training protocol), CF
      decreased by 11% (from 64 to 53%). On day 11, there was no fatigue evident in the
      experimental group; CF in all animals increased by 2-8%. On day 16, there was
      also no fatigue evident in the experimental group; CF increased by 0-9%. An
      additional 20 min of continuous contraction (15 BPM) fatigue testing was
      performed on the muscle without rest between the tests. No fatigue was evident at
      the end of testing. Light microscopic analysis of latissimus dorsi muscle biopsy
      specimens taken on the days of testing showed no evidence of necrotic damage. Our
      investigations suggest that it may be possible to start muscle transformation
      immediately after mobilization and use the untrained latissimus dorsi muscle for
      cardiac assist immediately after surgery for short periods.

PMID- 8573854
TI  - Applicability of the latissimus dorsi muscle in situ as a biomechanical energy
      source.
AB  - The purpose of this study was to assess the applicability of the latissimus dorsi
      muscle in situ as an energy source for a circulatory assist device. A pneumatic
      chamber, devised by the authors, was inserted beneath the muscle and compressed
      by contractions of the muscle so that muscle contractile power was converted into
      pneumatic pressure. The optimal insertion position of the chamber beneath the
      latissimus dorsi muscle, and the influence of chamber size on generated pneumatic
      pressure, were investigated. The pneumatic chamber functioned better when it was
      placed in a proximal position (third intercostal space) than in a middle or
      distal position. Using a mock circuit, the performance of the pneumatic chamber
      as an energy source for a circulatory assist device was evaluated. The pneumatic
      chamber was able to generate power sufficient to drive a right ventricular assist
      device as far as stroke work was involved. When the pneumatic chamber was
      operated with a high afterload, it could even be an energy source for aortic
      counterpulsation.

PMID- 8573855
TI  - Force enhancement of skeletal muscle used for dynamic cardiomyoplasty and as a
      skeletal muscle ventricle.
AB  - Some patients with pre end-stage congestive heart disease do not receive a
      significant hemodynamic benefit from dynamic cardiomyoplasty because, during
      prolonged preoperative immobilization, their latissimus dorsi muscle (LDM)
      becomes extremely weak. It is the authors' hypothesis that the local
      administration of an anabolic steroid into an electrically stimulated LDM will
      produce a thicker and stronger muscle with significant resistance to fatigue. The
      electrical stimulation training protocol of sheep continued for 8 weeks. For
      localized anabolic steroid administration an osmotic pump was placed in a
      subcutaneous pocket and the catheter was introduced into the LDM. The contractile
      force of electrically stimulated and unstimulated control muscle was studied.
      Control data were calculated as 100% and all other data were corrected to
      control. After 4 weeks there was no decrease in contractile force. The change
      seen was from 88 to 100% with different preloads (10, 15, and 20 g/kg) and
      amplitudes of impulses (5 and 10 V). After 8 weeks, the LDM was more powerful
      than before electrical stimulation, with a change of 97-133%. Usually after 8
      weeks of electrical stimulation alone, contractile force decreases to 70-75%.
      During a fatigue test (30 min, 100 bursts per minute, 10-25 Hz, ripple frequency,
      10 V impulse amplitude) after 4 and 8 weeks of our protocol, the LDM lost only
      12% of its initial force, whereas control muscle lost 40%. Thus local anabolic
      steroid administration makes the LDM stronger and more useful for
      cardiomyoplasty.

PMID- 8573856
TI  - Nuclear scanning with technetium-99m-sestamibi to evaluate ischemia in muscle
      flaps for cardiomyoplasty.
AB  - Mobilization of the latissimus dorsi muscle from the chest wall for
      cardiomyoplasty interrupts part of its blood supply. The time required for
      adequate collaterals to develop from the thoracodorsal artery is unknown. In four
      dogs, the latissimus dorsi muscle was mobilized as for cardiomyoplasty and
      stimulating electrodes were implanted. The muscle was replaced on the chest wall
      over a sheet of Gore-Tex (W. L. Gore & Associates, Inc. Flagstaff, AZ) membrane
      to block growth of collateral vessels from the chest wall. The opposite
      latissimus dorsi muscle served as the control. After a delay of 2 weeks the
      latissimus dorsi was burst stimulated at a rate of 80 per min with two 100 msec
      bursts at 85 Hz and 25 Hz for 30 min. Technetium-99m-sestamibi scans were then
      done to detect ischemia. Serial studies were done during the next several weeks.
      Images at 4 weeks demonstrated maximum uptake in the mobilized muscle, which did
      not subsequently improve. The authors conclude that the mobilized latissimus
      dorsi muscle can be imaged with technetium-99m-sestamibi and evidence of ischemia
      resolves at 4 weeks. These findings suggest that collateral flow is adequate as
      early as 4 weeks after mobilization of the latissimus dorsi muscle for
      cardiomyoplasty.

PMID- 8573857
TI  - Prolonged total circulatory support using direct mechanical ventricular
      actuation.
AB  - Direct mechanical ventricular actuation (DMVA) is a unique, non blood contacting
      method for biventricular cardiac assist. Although DMVA has successfully provided
      cardiac assist for more than 7 days in humans, with long-term survival, its
      potential for long-term circulatory support has not been adequately investigated.
      DMVA has not been studied in the large ruminants commonly used to evaluate
      support devices. To develop a large animal experimental model of prolonged total
      circulatory support using DMVA, Suffolk sheep (n = 10) underwent sterile
      instrumentation for hemodynamic and chemistry monitoring. After baseline values
      were obtained, a left lateral thoracotomy and pericardotomy were performed. Upon
      electrical ventricular fibrillation (VF), DMVA was begun and the thoracotomy
      closed. Total circulatory support was continued until mean arterial pressure
      (MAP) persisted below 50% of the baseline value for more than 1 hr, with a goal
      of 7 days' support. Mean duration (plus or minus the standard deviation [SD]) of
      circulatory support was 65.9 +/- 56.8 hr (range, 10-168 hr). Pressors were not
      used during DMVA support. The subject supported for the maximal time (7 days) was
      defibrillated into sinus rhythm. No CK-MB fraction was greater than 1%,
      suggesting that DMVA, even with prolonged application during VF, does not result
      in myocardial injury. Blood urea nitrogen and creatinine levels indicate renal
      function was preserved. The model described represents the longest period any
      animal has been supported in VF using DMVA. This new model will be useful in
      determining what limitations, if any, exist to the prolonged use of DMVA for
      circulatory support.

PMID- 8573858
TI  - Left atrial or ventricular cannulation beyond 30 days for a Thoratec ventricular
      assist device.
AB  - The authors used Thoratec left ventricular assist devices (VADs) for more than 30
      days in eight patients. There were five left atrial (LA) (total, 513 days; range,
      33-202 days) and three left ventricular (LV) cannulations (total, 484 days;
      range, 44-247 days). The flow provided by LA cannulation was less than that
      provided by LV cannulation. However, serial measurements of hematologic, renal,
      and hepatic function were similar for patients with LA and those with LV
      cannulation throughout support. Plasma free hemoglobin and lactate dehydrogenase
      (LDH) levels were similar for LA and LV patients. The five LA patients had one
      transient ischemic attack, one reversible ischemic neurologic deficit, and one
      stroke. The LV patients had no neurologic events (p = 0.20; LA versus LV total
      neurologic events). One LA patient and one LV patient died during support. Three
      LA patients underwent transplant, and one LA patient recovered native cardiac
      function. Two LV patients underwent transplant. In certain situations (e.g.,
      recent anterior myocardial infarction; small left ventricular dimensions) LA
      cannulation may be advantageous. Neurologic events may be more common in LA
      patients, but in our small group this difference could be attributable to chance
      alone. LA or LV cannulation for a Thoratec VAD can provide adequate circulatory
      support for more than 30 days.

PMID- 8573859
TI  - Clinical experience with long-term use of the Toyobo left ventricular assist
      system.
AB  - The Toyobo-NCVC extracorporeal pneumatic left ventricular assist system (LVAS)
      was used in four patients with advanced dilated cardiomyopathy. The duration of
      support ranged from 46 to 390 days (mean, 206 days). In all patients, stable
      hemodynamics were achieved with 3.5-5.5 L/min flow rates. Two patients survived
      long term. One was transported to the United States by a chartered jet while on
      LVAS and successfully underwent heart transplantation after 119 days of support.
      The other is on LVAS and is doing well for 390 days. The remaining two patients
      died of multi-organ failure while their hemodynamics were quite stable under
      LVAS. In these two patients, severe hepatic failure had developed before LVAS
      implantation. Minor cerebral embolisms occurred in the two survivors, but neither
      of them experienced permanent neurologic deficits. In only the initial patient
      were major thrombi noted on the diaphragm of the pump; the thrombi required pump
      exchange four times during 119 days. In the patient supported for 390 days, a
      small tear in the diaphragm was observed after 209 days of support, and the pump
      was safely exchanged. It is suggested that the Toyobo LVAS can provide consistent
      and reliable performance for long-term use.

PMID- 8573860
TI  - Long-term circulatory support to promote recovery from profound heart failure.
AB  - In profound heart failure, ventricular assist systems (VAS) have been used to
      maintain the systemic circulation and promote recovery of the failing heart. The
      authors' data suggest that the heart may not recover sufficiently if the patient
      needs left ventricular assist beyond 10 days. Recently, the authors treated six
      patients who were supported by VAS more than 3 weeks and were weaned from VAS.
      Four of six patients were weaned from VAS and continue well, despite marginal
      cardiac function. In the other two patients, the natural heart did not sustain
      stable recovery, but their general conditions made them fit to be candidates for
      heart transplantation. Based on these data, long-term support should be
      considered to promote recovery of heart function with the use of VAS for profound
      heart failure.

PMID- 8573861
TI  - Long-term left ventricular assist device use before transplantation.
AB  - Between September 1992 and April 1995, 19 patients at the authors' institution
      received pneumatic, pulsatile left ventricular assist devices (LVADs) for
      bridging to cardiac transplantation. The mean (+/- SD) age of the patients was 51
      +/- 14 years (range, 19-64 years). Nine (47%) patients had end-stage idiopathic
      cardiomyopathy, five (26%) had ischemic cardiomyopathy, and five (26%) other
      recipients were in cardiogenic shock caused by acute myocardial infarction (AMI).
      Fifteen (79%) patients were supported with an intraaortic balloon pump or
      centrifugal LVAD at the time of LVAD insertion (duration, 5.5 +/- 4.1 days).
      Aprotinin was given to limit bleeding; heparin, followed by warfarin sodium, was
      used for anticoagulation. A vigorous exercise and nutrition protocol was
      followed. Cardiac index averaged 2.94 +/- 0.87 L/min/m2 immediately after the
      implantation procedure. No patient required placement of a right VAD. Average
      duration of LVAD support was 45 +/- 39 days (range, 3-153 days). Major
      complications included bleeding requiring reoperation (three patients);
      cerebrovascular accident (three patients); and severe dysrhythmias requiring
      direct current cardioversion (four patients). Fourteen (74%) patients underwent
      transplantation, with one patient still being mechanically supported. All of the
      patients receiving transplants were discharged from the hospital. Of the
      individuals who died while supported with the LVAD, 75% were patients with AMI.
      Timely application of LVADs as part of the interdisciplinary management of end
      stage heart disease has generated excellent results for transplant candidates.
      Right ventricular dysfunction has not necessitated right VAD placement in the
      authors' experience. Patients with AMI have a higher risk of death while being
      supported with the device than do more chronically ill recipients.

PMID- 8573862
TI  - Hospital charges for conventional therapy versus left ventricular assist system
      therapy in heart transplant patients.
AB  - An important goal of a left ventricular assist system (LVAS) is to provide long
      term, safe, cost-effective mechanical circulatory support. The Heartmate LVAS
      (Thermo Cardiosystems, Inc., Woburn, MA), used in recent clinical trials as a
      bridge to transplantation, has proven extremely reliable for long periods, and
      its use has improved the survival rates in patients who subsequently received a
      donor heart. Patients who have been implanted with an LVAS often have
      significantly improved physical status and can leave the intensive care unit
      (ICU) and be treated at less expense elsewhere in the hospital. In this
      preliminary report, the authors analyzed hospital charges for three groups of
      patients: heart transplant patients who received conventional medical therapy
      before transplantation (Group 1), transplant patients who received in-hospital
      LVAS therapy (Group 2), and one patient who awaited transplantation at home while
      undergoing LVAS support. Group 1 patients (n = 6) received intraaortic balloon
      pump (IABP) support and inotropic therapy in an ICU before transplantation. Group
      2 (n = 6) patients were receiving IABP support and inotropic therapy when the
      LVAS was implanted and eventually underwent heart transplantation. The length of
      hospital stay in Group 1 (51 days) was significantly shorter than in Group 2 (185
      days). Mean hospital charge in Group 1 was $5,150/day; in Group 2, $3,178/day.
      The patient living at home incurred an average medical expense of $27/day.
      Although LVAS supported patients remain in the hospital much longer than do
      medically treated patients, their average daily in-hospital charges are much
      less. If the LVAS could be used as an alternative to transplantation, it might
      offer not only a longer, better quality life, but also a potential cost savings
      to patients with end-stage heart failure.

PMID- 8573863
TI  - Protocol for releasing Novacor left ventricular assist system patients out-of
      hospital.
AB  - Between September 1984 and April 1995, the Novacor left ventricular assist system
      (LVAS) has provided more than 13,000 days of mechanical circulatory support to
      cardiac transplant candidates in the United States and Europe. The duration of
      support of these 312 patients has ranged between 1 and 370 days, with an average
      support of 40 days, including use of the console based system and the wearable
      system. Of this group, 21% have been supported for more than 60 days, with an
      average support of 118 days. We have seen that patients who have been supported
      for more than 30 days have recovered from the effects of LVAS implant surgery and
      have shown a potential for rehabilitation from morbid congestive heart failure.
      Few changes to the pump settings or the medical orders have been needed after the
      third postoperative week. The reliability of the LVAS and the degree to which
      patients can be rehabilitated suggest that restricting patients to a hospital
      environment is unnecessary. In addition, the increasing wait for a donor heart,
      the quality of life that can be achieved, and the high cost of inpatient care
      make it desirable to discharge patients from the hospital and allow them to await
      a donor heart in a more home-like setting.

PMID- 8573864
TI  - Estimation of left ventricular function in patients with a left ventricular
      assist device.
AB  - Patients with profound left ventricular (LV) dysfunction supported by a left
      ventricular assist device (LVAD) may have recovery of LV function, but current
      methods for assessing this are difficult or not readily available. A new method
      to estimate LV performance was tested in 6 patients on LVAD (age, 47 +/- 12
      years). Simultaneous measures of LV cross-sectional area (substitute for volume)
      using transesophageal echocardiographic automated border detection and femoral
      arterial pressure (substitute for LV ejection pressure) were recorded during
      brief periods on and off LVAD. During the LVAD off period, femoral arterial
      pressure and LV area signals were combined on-line to generate arterial pressure
      LV area loops. The slope of the linear regression line connecting the end
      systolic points generated during LV filling after LVAD off was used as an
      estimate of end systolic elastance denoted by Ees. The average Ees was 3.8 +/-
      3.1 mmHg/cm2. These values are significantly lower than those of 13 control
      patients (22.3 +/- 15.4 mmHg/cm2). This method of estimating Ees may be
      clinically useful in assessing LV recovery in patients on LVAD after extended
      support.

PMID- 8573865
TI  - End organ function with prolonged nonpulsatile circulatory support.
AB  - The hypothesis tested in these studies was that long-term circulatory support
      with a nonpulsatile device is safe and causes no end organ dysfunction. An
      inexpensive, small centrifugal pump with a 7 L/min capacity was implanted in 6
      sheep (15 acute implants have previously been reported). The inlet cannula was
      placed in the left atrium and the outlet graft anastomosed to the descending
      aorta. A percutaneous cable supplied DC power and heparinized saline (10 ml/hr)
      for lubrication. Outputs of pump flow, stator, animal core temperature, pump
      power consumption, and RPM were monitored throughout the course of each
      experiment. The sheep moved freely within a large pen using an overhead
      swivel/tether system that carried all input and output lines. Four sheep survived
      longer than 4 weeks, and the indices of end organ function were analyzed at 28
      days. No animal revealed any neurologic dysfunction. Hemoglobin was 9.075 +/-
      0.78 g/dl at 28 days, as opposed to 7.475 +/- 0.68 (p = 0.002) before surgery.
      The blood urea nitrogen was 9.250 +/- 4.57 versus 14 +/- 5.72 mg/dl (p = 0.041),
      creatinine was 0.775 +/- .10 versus 0.775 +/- 0.05 mg/dl (p > or = 0.999), total
      bilirubin was 0.425 +/- 0.2 versus 0.225 +/- 0.05 mg/dl (p = 0.092), serum
      glutamic oxaloacetic transaminase was 74.75 +/- 24 versus 106.25 +/- 15.84 IU/L
      (p = 0.015), serum glutamic pyruvic transaminase was 36 +/- 28.7 versus 28.3 +/-
      5.7 IU/L (p = 0.25), and total protein was 6.675 +/- 0.49 versus 5.47 +/- 0.15
      g/dl (p = 0.025). It is concluded that these animals adapted very well to
      pulseless circulatory support. The results of these studies support the concept
      of an inexpensive, implantable, centrifugal pump as a ventricular assist device.

PMID- 8573866
TI  - An atraumatic aspirator for use in autologous transfusion and cardiac bypass.
AB  - Surgical aspiration has long been seen as the weak link in surgical blood
      recovery. Aspiration causes a high degree of hemolysis that leads to high plasma
      hemoglobin levels and reduces the number of erythrocytes available for
      reinfusion. Aspiration also damages platelets, generates emboli, and increases
      bleeding time. The major source of the high hemolysis and the other blood damage
      that occurs during suction is the aspiration of air with the blood. To address
      this problem, a jet driven aspirator that immediately separates and removes air
      during suction was designed and tested. The aspirator suctions blood at a range
      of rates from 100 to at least 700 ml/min, separates and removes 80-100% of the
      aspirated air, operates at any orientation, and generates subatmospheric
      pressures on the order of only an inch of water. During in vitro hemolysis
      testing, the removal of air by the jet driven aspirator showed a significant
      reduction in hemolysis: plasma hemoglobin levels increased 19.4 mg/dl without air
      removal and only 1.8 mg/dl with air removal (p < 0.001). In comparative testing
      with a conventional vacuum operated suction tube, the jet driven aspirator showed
      significantly less hemolysis (p < 0.001) than did the conventional aspirator at
      comparable blood and air aspiration rates.

PMID- 8573867
TI  - Long-term cardiopulmonary support with a composite artificial heart-lung system.
AB  - A novel cardiopulmonary support (CPS) system as a long-term total substitute for
      the natural heart and lung was designed and evaluated. The CPS system is composed
      of a ventricular assist device (VAD) and a newly developed compact artificial
      lung (AL). The pneumatic VAD was originally developed in the authors' institute
      and has proven durable and antithrombogenic in over 120 clinical uses. The AL,
      with 1.2 m2 membrane surface area and 140 ml priming volume, consists of a
      special gas exchange membrane where not only are micropores blind-ended to
      prevent serum leakage, but the blood contacting surface is treated with heparin
      binding to ease systemic anticoagulation. Chronic animal experiments of total CPS
      were carried out in three goats weighing from 28 to 36 kg. Venoarterial bypass
      was instituted with the CPS system in which all venous blood was drawn from both
      the right atrium and ventricle and returned to the aorta. No systemic
      anticoagulation was conducted except for heparin added fluid infusion from
      pressure lines. One animal survived for 2 weeks without any device related
      problems until electively euthanized. Blood flow rate ranged between 3.2 to 4.5
      L/min, O2 transfer between 120 to 220 ml/min, and CO2 removal between 60 to 210
      ml/min. No substantial changes were found in platelet count or other coagulation
      factors. These results indicate that the system has the ability to be used for
      long-term CPS, such as a bridge to lung or heart-lung transplantation.

PMID- 8573869
TI  - Stragegies to reduce surface area requirements for carbon dioxide removal for an
      intravenacaval gas exchange device.
AB  - Experimental and clinical use of the intravascular oxygenator (IVOX), an
      intravenacaval gas exchange device, in acute respiratory failure yielded a CO2
      transfer of 40-70 ml/min (approximately 30% of adult CO2 production) at
      normocapnia. Although significant, this rate of CO2 removal is not clinically
      useful. To maximize CO2 transfer, given the same gas exchange properties and
      structure design of the IVOX, the authors analyzed the effects of permissive
      hypercapnia (stepwise increase in arterial blood pCO2 up to 100 mmHg) and active
      blood mixing (with an intraaortic balloon pump) on different sizes of IVOX (sizes
      7, 8, and 9 mm, surface area 0.21, 0.32, and 0.41 m2, respectively) using a
      previously established ex vivo circuit to model the human vena cava. The CO2 net
      transfer coefficient (KCO2) was averaged for all sizes and applied to extrapolate
      the surface area requirements under different pCO2 and with active blood mixing.
      Results showed that KCO2 increased in a linear relationship with blood flow.
      Increases in blood flow and blood pCO2 further increase CO2 removal and decrease
      surface area requirements. For blood flow at 4.0 L/min, the membrane surface area
      required for 150 ml/min CO2 removal at blood pCO2 of 40 mmHg is 1.76 m2, but can
      be decreased to 0.47 m2 at blood pCO2 of 80 mmHg, and further to 0.42 m2 with
      additional active blood mixing. A 0.42 m2 surface area is associated with an O2
      transfer of 80 ml/min without and 107 ml/min with active blood mixing. It is
      concluded that CO2 removal by IVOX alone is limited by insufficient surface area
      and the resistance in the blood-surface boundary layer. The combination of
      permissive hypercapnia, adequate blood flow, and active blood mixing can
      substantially improve CO2 removal and can therefore achieve clinically
      significant CO2 removal by intravenacaval gas exchange devices during severe
      respiratory failure.

PMID- 8573868
TI  - Evaluation of a new heparin bonding process in prolonged extracorporeal membrane
      oxygenation.
AB  - A novel heparin bonding method has been developed for in situ surface
      modification using ozone oxidation, and evaluated in vitro and in vivo during
      prolonged extracorporeal membrane oxygenation (ECMO) experiments. The ECMO system
      consisted of a Capiox hollow fiber membrane oxygenator (MO; Terumo Corp., Tokyo,
      Japan) with an integral heat exchanger, a Capiox centrifugal pump (CP), and an
      extracorporeal circuit. The blood contacting surfaces of the system were
      completely modified using the heparin bonding process, and evaluated in a chronic
      sheep model for extended period of time, ranging from 96 to 168 hr, under minimal
      systemic heparinization. The heparin bonded surface was able to maintain high
      levels of heparin bioactivity, and showed improved blood compatibility in in
      vitro epifluorescent video microscopy experiments by suppressing platelet
      adhesion/activation and complement activation. For the ECMO experiments,
      extracorporeal blood flow was maintained at 3 L/min and the activated clotting
      time was maintained at 150 sec. There was no significant change in the gas
      transfer capability or mean pressure drop across the MO over experimental times
      of up to 168 hr. Platelet count and other coagulation parameters remained stable
      within the physiologic range throughout the experiment. There were no detectable
      thrombi in the CP, tubing, or connectors in the test circuit. Local thrombus
      formation was noted in a stagnant area of the MO, although this did not interfere
      with its function or lead to any significant embolization. Based on these
      results, the heparin bonded ECMO system appears to be a safe and effective device
      for prolonged extracorporeal circulation under minimal systemic heparinization.

PMID- 8573870
TI  - A matched pairs analysis of venoarterial and venovenous extracorporeal life
      support in neonatal respiratory failure.
AB  - It has been suggested that venovenous (VV) extracorporeal life support (ECLS)
      confers a survival advantage over venoarterial (VA) ECLS. These results have been
      confounded by differences in patient populations. In this study, a matched pairs
      comparison of survival and complication rates in neonatal respiratory failure
      patients managed with VA or VV ECLS was performed. Retrospective matching of 643
      VA and VV patient pairs from the Extracorporeal Life Support Organization
      Registry was performed. Pairs were matched by same year, same diagnosis,
      gestational age +/- 1 week, birth weight +/- 0.3 kg, and oxygenation index +/- 5.
      Further matching for hemodynamic status was possible for 272 pairs and included
      pre ECLS CPR, use of epinephrine, and arterial pH +/- 0.1. Statistical
      significance was defined for outcome and selected complication rates using
      McNemar's chi-square analysis with correction for multiple comparisons. A
      survival advantage for VV was significant when matching for respiratory failure
      (83.8% VA versus 91.5% VV), but was not significant when matching for hemodynamic
      failure (90.4% VA versus 94.5% VV). In the latter match, hemolysis (10.7% VA
      versus 23.5% VV) and cannula kinking (0.4% VA versus 10.6% VV) were more common
      with VV ECLS. The incidence of intracranial hemorrhage did not significantly
      differ between groups (6.3% VA versus 7.4% VV). Survival is not significantly
      greater with VV ECLS when patients are matched for degree of respiratory and
      hemodynamic failure. Hemolysis and cannula kinking are more common with VV ECLS.
      There is no identified difference in the incidence of intracranial hemorrhage.

PMID- 8573871
TI  - Effects of timing on ventriculoarterial coupling and mechanical efficiency during
      intraaortic balloon pumping.
AB  - To evaluate the effects of deflation timing of an intraaortic balloon (IAB) on
      ventriculoarterial (VA) coupling and left ventricular (LV) mechanics, we assessed
      contractility: Emax (mmHg/ml); VA coupling: Ea/Ees; myocardial oxygen
      consumption: LV pressure-volume area (PVA); and energy efficiency: external work
      (EW)/PVA during IAB pumping, using four different timing intervals of IAB
      deflation in eight dogs weighing 19.8 +/- 3.8 kg. In the conventional timing
      group (G-conv), the IAB was deflated before LV systole. In the real time group (G
      1, 2, 3), the IAB was deflated during isovolumic contraction (ICP), and the group
      was subdivided into three groups based on time of deflation: G-1 at the onset of
      ICP, G-2 at the midpoint of ICP, and G-3 at the end of ICP. Percent changes in
      values with IAB compared to those without assist were calculated. Based on the
      results, IAB deflation during ICP reduces LV end-systolic pressure and
      significantly optimizes VA coupling and LV efficiency during IAB support,
      compared with conventional timing.

PMID- 8573872
TI  - A two stage axial flow pump. New approach to reduction of hemolysis.
AB  - From an engineering point of view, the suitable revolution number for high
      efficiency operation of an axial flow pump is known. A multistage axial flow pump
      is a useful tool for reducing revolution number with a high efficiency axial flow
      pump. A two stage (25) axial flow pump designed at a 5 L/min flow rate and a 100
      mmHg pressure head was evaluated in three kinds of in vitro hemolysis tests. Each
      stage design point of the 2s pump was tested at a 5 L/min flow rate and a 50 mmHg
      pressure head. Specific speed and revolution number of the 2S pump were 1400 rpm,
      m3/min, m, and 15500 rpm, respectively. In the first test the 2S pump was
      compared with two single stage axial flow pumps (1S-A and 1S-B100) designed by
      the same method. The specific speed of the 1A was the same as that of the 2S
      pump, which was driven at 26000 rpm. The impeller of the 1S-B100 was the same as
      that of the 2S pump, which was driven at a 22000 rpm RN and a 1100 specific
      speed. The 2S pump was separated into two single stage axial flow pumps and the
      effect of series operation on hemolysis was evaluated in the second test. In the
      third test the 2S pump was compared with the 1S-B100 by using diluted goat blood
      samples with three different hematocrit values. The results showed that the
      hemolysis index of the 2S pump, regarded as a total hemolysis index of both stage
      axial flow pumps, was less than those of the single stage axial flow pumps at all
      hematocrit values.

PMID- 8573873
TI  - A gait-powered autologous battery charging system for artificial organs.
AB  - The quality of life of patients relying on electrically powered artificial organs
      is currently restricted by the limited energy availability provided by portable
      batteries. As these patients become increasingly ambulatory, and are developing
      more active lifestyles, this limitation grows more apparent. Coincidentally,
      these patients may themselves be capable of generating electrical power as a
      consequence of their physical activity. Extraction of this latent autologous
      energy could, in turn, be used to augment charging of internal batteries--thus
      untethering the patient from external power for extended periods of time. In this
      study, the viability of deriving energy associated with natural human ambulation
      has been evaluated. The kinematic components of gait were evaluated to identify
      the largest useful forces and moments that may be harnessed as an energy source,
      while presenting minimal "perceived" work for the patient. It was found that the
      ground reaction forces associated with the heel strike and toe-off phases of the
      gait represent the greatest potential for usable energy. This study uses a
      piezoelectric array within the midsole of the shoe for the conversion of
      mechanical to electric energy. This power could then be easily coupled in tandem
      with existing transcutaneous transformers for augmenting or temporarily replacing
      external power sources.

PMID- 8573874
TI  - Comparison between pulsatile and nonpulsatile circulatory assist for the recovery
      of shock liver.
AB  - In patients with prior shock and liver injury, mechanical circulatory assist
      still has a high risk of hepatic failure. The purpose of this study was to
      evaluate the effect of mechanical circulation using pulsatile or nonpulsatile
      blood pumps on shock organs, particularly shock liver. In 14 dogs, a shock liver
      model was produced by clamping the descending aorta above the diaphragm. After 60
      minutes of ischemia, left atrial-femoral artery bypass (LHB) was started while
      the clamp remained in place. A pneumatic pulsatile pump (Toyobo; Tokyo, Japan)
      was used in seven dogs (Gr-PP) and a centrifugal pump (Biomedicus; Minneapolis,
      MN) in seven (Gr-NPP). In both groups the mean arterial pressure was maintained
      at 80 mmHg. The mean bypass flow was 96 +/- 14 ml/kg/min for Gr-PP, and 95 +/- 35
      ml/kg/min for Gr-NPP. In both groups the bile flow and arterial ketone body ratio
      decreased significantly after ischemia, and recovered to normal after 120 min of
      LHB. There was no significant difference between the two groups in this model.
      The other parameters (glutamic oxaloacetic transaminase [GOT], glutamic pyruvic
      transaminase, lactate dehydrogenase, mitochondrial GOT) were independent of the
      period of ischemia and reperfusion, and there was no difference between the two
      groups. In conclusion, these results suggest that nonpulsatile circulatory assist
      may not be disadvantageous for the circulatory support and recovery of liver
      function in the setting of shock liver.

PMID- 8573875
TI  - Development of a new endotoxin sensor with intermittent injection of limulus
      reagent for continuous monitoring of dialysate fluid.
AB  - This report describes a method of continuously, stably, and inexpensively
      measuring endotoxin (ET) concentrations in dialysate fluid using an ET sensor
      with intermittent injection of limulus reagent. An ET solution simulating
      dialysate fluid was sampled in a single tube at a flow rate of 260
      microliters/min and mixed with 30 microliters of limulus reagent intermittently
      injected into the tube. The absorbance of the solution was measured after the
      limulus reaction at 313 or 318 degrees K at 26 min. A good linear relationship (r
      = 0.98) between peak area of absorbance and ET concentration at ET concentrations
      ranging from 0 to 0.12 endotoxin unit (EU)/ml was obtained, using a
      spectrophotometer with a cell volume of 8 microliter. The baseline rose after the
      measurements were taken because the cell volume was so small that the cell was
      stuffed with gel. A good linear relationship (r = 1.00) at ET concentration of
      0.1-0.25 EU/ml was also obtained, and the baseline was unchanged after
      measurements, using a metal free spectrophotometer with a cell volume of 420
      microliters. In conclusion, to measure ET concentrations below 0.1 EU/ml, the
      cell volume of a metal free spectrophotometer should be minimal.

PMID- 8573876
TI  - Replacement of long segments of the esophagus with a collagen-silicone composite
      tube.
AB  - Artificial esophagi designed thus far can be classified into three types in terms
      of the materials used: natural, artificial, and composite. In conventional
      models, even when artificial esophagi were made of ideal materials with high
      tissue affinity, they remained in the tissue as a foreign body, and therefore
      were not free of the complications caused by implanted material. The authors have
      designed a new type of artificial esophagus composed of a Silicone tube covered
      with nonantigenic collagen. The novel feature of this artificial esophagus is
      that the prosthesis does not remain in the implanted site, but is replaced by
      regenerated host tissue. Using this artificial esophagus, the authors have
      already succeeded in replacing a 5 cm gap in the esophagus. In this study,
      replacement of longer portions of the esophagus was assessed in seven dogs using
      a 10 cm long artificial esophagus. Stenosis did not occur in five of the seven
      dogs and, consequently, these dogs survived by oral feeding alone for more than 6
      months without dry weight loss. The other two animals died of anesthetic
      accidents at the time of stent removal 6 weeks after surgery. In both cases, the
      internal surface of the neoesophagus was covered with a polylayer of squamous
      epithelium. Regenerated esophagi had normal esophageal glands and immature muscle
      tissue. It is therefore concluded that this new artificial esophagus is also
      applicable for replacement of long segments of esophagus.

PMID- 8573877
TI  - A new microporous polyurethane vascular graft prepared by an excimer laser
      ablation technique.
AB  - Three types of polyurethane (PU) based tubes (internal diameter, 2 mm; wall
      thickness, 100 microns) with micropores of well controlled size and arrangement
      were fabricated using an excimer laser (KrF) ablation technique. The pore size
      (100 microns) and the longitudinal pore-to-pore distance (200 microns) were
      constant, and the circumferential pore-to-pore intervals were 60 degrees (type
      1), 30 degrees (type 2), and 15 degrees (type 3). The surface of the fabricated
      tube was photochemically modified with photoreactive gelatin. Scanning electron
      microscopy showed that pore size and arrangement were precisely controlled as
      designed, and that a gelatinous layer thoroughly covered the luminal surface. The
      stiffness parameter (beta), inversely related to compliance, was determined from
      the change in external diameter against intraluminal pressure. An increase in the
      number of pores around the circumference decreased the beta value. The type 1
      tubes implanted preliminarily in rats for 4 weeks showed good patency (80%). The
      combination of excimer laser-directed microporing and photochemical surface
      processing techniques enabled the development of a novel compliant small caliber
      vascular graft, which is expected to show enhanced transmural tissue ingrowth in
      vivo.

PMID- 8573878
TI  - Assessment of reused catheters.
AB  - Demands for health care cost containment have prompted the assessment of
      recycling medical devices, including catheters. The investigation of catheter
      reuse for effectiveness and safety began at the University of Ottawa Heart
      Institute in early 1994. This report provides the preliminary results from this
      ongoing assessment on the feasibility of catheter reuse. Burst tests were
      conducted to detect changes in catheter mechanical integrity. Scanning electron
      microscopy (SEM) was performed to assess surface changes and protein deposition
      after use and the subsequent cleaning process. Results of burst testing showed no
      significant difference in burst patterns or burst pressures between single use
      and unused catheters. Surface differences were observed between used and unused
      catheters. SEM studies detected physical changes such as scratches, gouges, cuts,
      and deposits on the used catheters. Unused balloon surfaces appeared to be clean
      and uniform compared to used ones. Residue and cracking were identified on other
      used devices. In conclusion, the methods used can assess various effects of
      recycling. A blind study of large samples of used catheters is planned to
      establish statistically the level and variance of structural damage to catheters
      during typical use.

PMID- 8573879
TI  - Noninvasive follow-up of tissue encapsulation of foreign materials. Are magnetic
      resonance imaging and spectroscopy breakthroughs?
AB  - The development of sensitive and noninvasive magnetic resonance (MR) techniques
      for the long- and short-term evaluation of vascular prostheses requires detailed
      knowledge of the evolutionary trend of the MR properties of the perigraft tissue
      during the healing process. To characterize changes in water MR properties, the
      water proton relaxation times, T1 and T2, of the muscle in the vicinity of an
      implanted polyester material were measured as a function of implantation time. To
      provide better insight into interpretation of the MR results, we carried out
      histologic and peripheral blood cell activation studies and tissue water content
      measurements. The MR results illustrated the sensitivity of the relaxation times
      to changes in cellular response to the presence of an implant. The evolutionary
      trend of these MR parameters exhibited two distinct phases. The crossover from
      phase I to phase II occurred around 10 days postimplantation. This crossover is
      attributed to the transition in the inflammatory response from the acute phase to
      the chronic phase. During the acute phase, the very high initial T1 and T2s (the
      slower relaxing component of the transverse relaxation time) values decreased
      significantly and steadily. The value of T1 dropped by a factor of 2, whereas T2s
      went down by a factor of 6. During the same time, the diffusion parameter, beta,
      remained constant. However, during the chronic phase, the diffusion parameter
      increased sharply. By 30 days postimplantation, the value of beta had increased
      by a factor of 10. The relaxation times, on the other hand, increased steadily
      with implantation time. Because the current MR results provide an in vivo and
      noninvasive follow-up of the healing process around the polyester implant
      material, they will be of considerable value in the early detection of vascular
      graft complications by MR imaging.

PMID- 8573880
TI  - Effects of radiofrequency glow discharge and oligopeptides on the attachment of
      human endothelial cells to polyurethane.
AB  - Activation of the surface of small diameter polyurethane vascular grafts using
      radiofrequency glow discharge (RFGD) and covalent linkage of cell attachment
      oligopeptides may improve graft patency. The effects of RFGD treatment were
      investigated on a polyurethane-polydimethylsiloxane (PU-PDMS) copolymer
      (Cardiothane-51; Kontron Cardiovascular, Inc., Everett, MA) membrane fabricated
      using the spray, phase-inversion technique. RFGD using H2O vapor was used to
      functionalize the membrane surface, reacted with 1',1 carbonyldiimidazole and
      covalently bound with oligopeptides (RGDS, RGES). Membranes not subjected to
      RFGD, either unmodified or with adsorbed fibronectin (Fn), vitro-nectin (Vn),
      RGDS, RGDV, and RGES, were used as controls. RFGD treated membrane surfaces were
      evaluated using electron spectroscopy for chemical analysis, which demonstrated a
      qualitative increase in nitrogen and silicon compared to unmodified PU-PDMS.
      Indirect confirmation of surface hydroxylation was provided by metallization with
      palladium and nickel, demonstrating uniform metallization of RFGD treated PU-PDMS
      surfaces. Human umbilical vein endothelial cells (HUVEC) were seeded at a density
      of 10(4) cells/cm2 and cell attachment assessed at 3 hr, 24 hr, and 7 days.
      Untreated PU-PDMS and membrane with adsorbed oligopeptides demonstrated poor
      HUVEC attachment at all intervals. Adsorbed Fn and Vn had significantly better
      early cell attachment and growth (p < 0.01). RFGD improved initial attachment and
      growth over non-RFGD treated controls (p < 0.01) for RGDS bound membranes, which
      performed as well as Fn controls (N.S.). PU-PDMS membranes can be modified using
      RFGD to covalently link oligopeptides. RFGD treatment alone, or with covalent
      linkage of cell attachment oligopeptides, improves HUVEC attachment and growth in
      a static environment.

PMID- 8573881
TI  - In vivo tissue distribution of fibroblast growth factor-1 after intraarterial
      delivery.
AB  - The clinical applicability of fibroblast growth factor-1 (FGF-1) plus heparin
      delivery in optimizing the healing of both autogenous vein and synthetic vascular
      grafts has been suggested. The authors have reported enhanced endothelial cell
      proliferation, concurrent increased capillarization, and minimal intimal
      hyperplasia using suspensions of FGF-1 and heparin impregnated onto expanded
      polytetrafluoroethylene grafts. The current study characterizes the tissue
      distribution of 125I-FGF-1 delivered by continuous intraarterial infusion. 125I
      FGF-1 delivered by continuous intraarterial infusion. 125I-FGF-1 (1.1 ng) and
      heparin (28 U) were continuously infused into the thoracic aorta via the proximal
      end of the ligated left carotid artery for 24 hr in four New Zealand white
      rabbits using an Alzet (Alza Corp., Palo Alto, CA) osmotically activated pumping
      device. Rabbits were sacrificed after 24 hr, exsanguinated, and biopsies taken
      from the liver, kidneys, spleen, lungs, heart, thyroid gland, muscle, and fat.
      These samples were assayed for radioactivity and results expressed as cpm
      125I/gram of both wet and dry weight of tissue. 125I-FGF-1 uptake (cpm/g dry wt.)
      was greatest in the thyroid (551.1 +/- 131.4). This was 2.5-5.5 x greater (p < or
      = 0.01) than those organs with intermediate uptake (lungs, liver, kidneys,
      spleen, and heart). Lowest uptake was noted in the blood, muscle, and fat. A
      similar distribution pattern was found in wet weight comparisons. Total organ
      125I-FGF-1 content was greatest in the liver at 818.1 +/- 176.3 cpm (p < or =
      0.002) and intermediate in the lungs (204.7 +/- 38.5 cpm) and kidneys (191.2 +/-
      11.9 cpm). Although no FGF-1-induced toxicity has yet been reported, these
      results will allow for future tissue-specific toxicology studies before clinical
      trials.

PMID- 8573882
TI  - The performance of commercially available sealed Dacron vascular grafts in
      intraarterial thrombolytic therapy.
AB  - The purpose of this study was to assess whether two commercially available,
      sealed arterial prostheses would tolerate catheter directed, intraarterial
      thrombolytic therapy. Sealed vascular grafts were implanted in 12 mongrel dogs
      for 3, 4, and 6 week intervals as iliac artery interposition grafts. This allowed
      direct comparison of two types of sealed grafts in the same animal. The
      indications for graft failure consisted of clinically evident bleeding,
      transluminal extravasation, or anastomotic leakage of contrast medium documented
      by angiography. Thrombolytic therapy (urokinase) was delivered immediately
      proximal to the grafts in the distal aorta, thereby exposing the intraluminal
      surfaces to urokinase delivered directly from the catheter tip, as well as to the
      accumulated systemic levels of urokinase and urokinase activated plasmin. There
      was no evidence of postoperative bleeding or extravasation of contrast medium
      during any follow-up arteriogram in any animal. There was no discernible
      extravasation of contrast medium noted at the anastomotic sites. At the time of
      explantation, no graft demonstrated any evidence of subclinical extravasation,
      such as separation of the external capsule from the abluminal surface of the
      graft. It is concluded that it appears safe to use thrombolytic therapy in these
      grafts as early as 3 weeks postimplantation.

PMID- 8573883
TI  - Perfluorocarbons are effective oxygen carriers in cardiopulmonary bypass.
AB  - Intravascular perfluorochemical (PFC) emulsions together with a high oxygen (O2)
      tension may increase the delivery of dissolved O2 to useful levels. A severely
      anemic model of cardiopulmonary bypass (CPB) was used to test the hypothesis that
      a novel PFC emulsion (PFCE; Oxygent [Alliance Pharmaceutical Corp., San Diego,
      CA] 90% w/v perflubron) used at a high PO2 during bypass delivers sufficient O2
      to ameliorate hypoxic myocardial contractile dysfunction. Acutely anemic dogs (N
      = 42; hematocrit = 15.8 +/- 0.6% [mean +/- SEM] before CPB and 10.9 +/- 0.1%
      during CPB) were divided into four groups. Group 1 was a control (n = 12). As CPB
      was initiated, groups 2 (n = 10), 3 (n = 10), and 4 (n = 10) had 1.35 g PFC.kg-1,
      2.7 g PFC.kg-1, or 5.4 g PFC.kg-1 added via the venous return cannula. Pre-CPB
      and post-CPB cardiac function was measured by the first derivative of left
      ventricular pressure (dP/dtmax). The dP/dtmax on separation from CPB was: group
      1, 619 +/- 96; group 2, 738 +/- 56; group 3, 782 +/- 101; and group 4, 828 +/-
      100 (p < 0.05 groups 3 and 4 versus group 1). Mortality during the first hour
      after separation from CPB was higher in group 1 than in PFCE treated dogs;
      however, this trend did not attain statistical significance (p < 0.065). The PFC
      dose was higher in survivors than in nonsurvivors (2.6 +/- 0.4 g PFC.kg-1 versus
      1.2 +/- 0.5 g PFC.kg-1; p < 0.05). A PFCE used at a high PO2 provides sufficient
      physically dissolved O2 to relieve myocardial hypoxic injury in a severely anemic
      model of CPB. Current PFCEs are effective O2 carriers. This finding suggests that
      they can be used as a temporary erythrocyte substitute to diminish the need for
      allogeneic transfusions during cardiac operations.

PMID- 8573884
TI  - Evidence for the direct inhibition of endothelin-1 secretion by hemoglobin in
      human endothelial cells.
AB  - The actual hemoglobin (Hb) contribution to endothelin-1 (ET-1) production in
      human umbilical vein endothelial cells (EC) was investigated. Cells were
      incubated with 0.1 mmol or 0.3 mmol of bovine: 1) unmodified (U) ferrous-Hb; 2) U
      ferric-Hb; 3) U-ferryl-Hb; 4) polymerized low molecular weight (m.w.) Hb with
      chemically modified surface (< 400 kDa); and 5) glutaraldehyde polymerized, high
      m.w. Hb (< 1020 kDa). The incubation medium was tested at 6 and 24 hr for lactate
      dehydrogenase (index of cellular injury), and for ET-1 release by the cells.
      Before radioimmunoassay, the ET-1 was extracted from cell culture medium by a two
      step purification procedure: 1) ultrafiltration, and 2) column extraction with
      C18 cartridges. The data suggested that the oxidation status of Hb and its
      concentration play an important role in causing EC injury. The highest toxicity
      was observed when EC were incubated with 0.1 mmol of ferryl-Hb, and there was no
      toxicity with 0.3 mmol of ferric-Hb. These results indicate that the ferric-Hb
      and low m.w. polymerized Hb at a concentration of 0.1 mmol did not alter ET-1
      synthesis and produced a level similar to that of the control. However, it was
      found that ferryl-Hb and ferrous-Hb in a concentration of 0.1 mmol significantly
      reduced ET-1 release. All Hbs at a concentration of 0.3 mmol markedly inhibited
      the production of ET-1. The greatest decrease in ET-1 levels was produced by
      ferryl-Hb, and the lowest by ferric-Hb and low m.w. polymerized Hb. The Hb's
      inhibitory effect was more pronounced at 24 hr of incubation. It was also found
      that although Hb molecules showed a high degree of cross-reactivity with
      polyclonal anti ET-1 antibodies, the presence of different Hb solutions in the EC
      culture medium did not change the immunologic properties of ET-1 peptide. In
      conclusion, Hb inhibitory activity toward ET-1 production might be related to Hb
      mediated endothelial oxidative injury.

PMID- 8573885
TI  - Biodegradable ceramic-collagen composite implanted in rabbit tibiae.
AB  - To develop an artificial bone substitute that would be gradually degraded and
      replaced by the regenerating natural bone, a carbonate apatite type I
      atelocollagen (82/12 in v/v%) composite was designed. The carbonate apatite
      synthesized at 58 degrees C demonstrated a crystallinity similar to that of
      natural bone. Type I atelocollagen was purified from human umbilical cords.
      Carbonate apatite-atelocollagen composite rods (diameter 6 mm x height 10 mm)
      were irradiated by ultraviolet ray (wave length 254 nm) for 4 hr to increase the
      collagen fibrillar cross links. Rabbit tibiae were dissected to prepare an
      artificial total bone defect (length 10 mm). The composites and porous
      hydroxyapatite rods, sintered at 1200 degrees C, were implanted into the defects
      and the tibiae were fixed by external osseofixators. The implanted composites
      were gradually degraded in the lesions, and the regenerated bone totally replaced
      the defects within 6 weeks, while the hydroxyapatite rod implanted lesions were
      not replaced by bone. No specific histologic abnormalities appeared in either the
      hydroxyapatite or composite rod implanted lesions.

PMID- 8573886
TI  - Experimental study of nerve regeneration in a biodegradable tube made from
      collagen and polyglycolic acid.
AB  - The authors developed a novel bioabsorbable nerve conduit to induce nerve
      regeneration across long gaps. It is a composite tube made of polyglycolic acid
      mesh coated with collagen. Seven cats underwent 25 mm resection of the left
      sciatic nerve. The proximal and distal nerve stumps were inserted into the tube
      and fixed with sutures to bridge the 25 mm gap between them. Histologic
      examination 4 months after implantation of the tube showed regeneration of nerve
      tissue structure, including myelinated axons and Schwann cells, and somatosensory
      evoked potentials and electromyograms demonstrated functional recovery of the
      regenerated nerves. Horseradish peroxidase staining revealed restoration of
      anterograde and retrograde axonal transport. These results indicate that this
      polyglycolic acid-collagen composite tube is promising as a nerve conduit that
      provides adequate nerve regeneration.

PMID- 8573887
TI  - Clinical application of disposable heparin sensors. Blood heparin measurements
      during open heart surgery.
AB  - The authors previously reported the development of an ion selective electrode
      type heparin sensor consisting of a specially formulated polymer membrane doped
      with tridodecylmethylammonium chloride as the heparin complexing agent. They also
      demonstrated the feasibility of measuring blood heparin levels by protamine
      titration, using a disposable copper wire sensor coated with the heparin sensing
      membrane to probe the titration end point. In this article, the results of
      further titration studies conducted on 44 clinical whole blood specimens obtained
      from 8 patients undergoing open heart surgery were reviewed. Samples were taken
      from patients at four different stages during the bypass surgery: 1) before
      heparin administration; 2) immediately after heparin administration; 3) within 30
      min to 3 hr after heparin administration; and 4) within 30 min after protamine
      administration. Heparin anticoagulant activity in these samples was monitored by
      the activated clotting time assay, whereas heparin concentrations were measured
      by protamine titration using either the Hepcon HMS Titrator (Medtronic HemoTec
      Inc., Englewood, CO) or the coated wire heparin sensor to determine titration end
      points. Results indicate that heparin levels determined by the sensor method were
      in good agreement with those determined by the Hepcon HMS Titrator. When the
      heparin concentrations estimated by the two methods show significant discrepancy
      (> 1.0 unit/ml), the sensor method seems to provide more precise values, as
      verified by an additional chromogenic heparin assay. The overall time required to
      complete the titration process and heparin measurement with a pre made heparin
      sensor was less than 3 min. Clinically, the heparin sensor could be used as a
      safeguard to precisely monitor heparin levels during surgical procedures.
      Alternatively, the sensor could be used to assess the accurate protamine dose
      required for full heparin reversal.

PMID- 8573888
TI  - A new fiber optic probe for cellular visualization.
AB  - Thrombus formation within artificial organs has been shown, at least in part, to
      be caused by retarded or stagnant blood flow. The goal of this work was to
      develop a magnifying fiber optic probe capable of visualizing particle flow and
      cellular deposition in a physiologically relevant cellular suspension (blood).
      The probe has minimal cross sectional area to allow for access to confined areas
      and to minimize flow disturbance. The probe consists of a germanium oxide fiber
      optic bundle and a gradient index imaging lens. Fluorescent microspheres of 48
      microns, 7 microns, and 3 microns in diameter were imaged after deposition on to
      a cover slip. The flow (1.44 mm/sec) of 3 microns microspheres suspended in
      buffer alone and with red cell hematocrits of 10%, 25% and 45% were also
      visualized. To investigate the potential for this probe to detect ongoing
      thrombosis, fluorescently labeled human platelets were observed depositing on
      surfaces from a stagnant platelet rich buffer. These initial data suggest that
      this probe may offer a technique for the visualization of blood cell adhesion on
      the interior of artificial organs and the local quantification of flow in such
      devices.

PMID- 8573889
TI  - Conductance-echocardiography correlation during changes in left ventricular
      volume.
AB  - Conductance (COND) measurements of left ventricular volume, satisfactory under
      steady state conditions, may be altered by extraneous factors during complex
      experiments or cardiac surgery. A reference technique is needed to detect changes
      in the COND-left ventricular volume relationship. This technique should indicate
      when recalibration of COND is needed. Accordingly, we assessed the relationship
      between left ventricular COND and the area of left ventricular short-axis cross
      section (SACS) by two-dimensional echocardiography during vena caval occlusion.
      Thirteen anesthetized pigs underwent a median sternotomy and insertion of a COND
      catheter. Two-dimensional echocardiography and COND were displayed and recorded
      simultaneously on a digital video monitor. Data were analyzed at end-diastole
      during the filling phase after vena caval occlusion, because the quality of two
      dimensional echocardiography was better during recovery. Results demonstrated a
      linear relationship between left ventricular COND and SACS at end-diastole, with
      a positive slope. Correlation coefficients ranged from 0.88 to 1.0 and averaged
      0.96 +/- 0.01 (SE). The overall mean relationship was (SACS) = 0.40 (COND) - 17.
      It is concluded that SACS by two-dimensional echocardiography can be employed to
      confirm COND measurements of left ventricular end-diastolic volume during
      laboratory experiments or cardiac surgery. Stability of the SACS-COND
      relationship indicates that COND calibration is valid. Changes in the SACS-COND
      relationship would require recalibration of COND. Data markedly deviating from a
      linear SACS-COND relation reflect experimental error and should be discarded.

PMID- 8573890
TI  - Geometry and temperature dependence of conductance ventriculography.
AB  - The conductance catheter allows continuous monitoring of ventricular volume in
      vivo, but shape and temperature dependence have not been defined. Accordingly, an
      in vitro experiment was performed to assess the potential utility of conductance
      for volume measurement during hypothermia and in asymmetric chambers resembling
      the right ventricle. A 5 Fr conductance catheter was placed inside an ellipsoidal
      latex balloon, and known volumes of normal saline were infused, while conductance
      volumes were measured. The geometry of the right ventricle was then approximated
      by compressing the balloon in a mandrel constructed of two hemi-cylinders.
      Measurements were repeated in this geometry. Temperature was varied at volumes of
      90 ml and 120 ml in an ellipsoidal balloon, and conductance was measured.
      Conductance volumes were plotted versus known volumes and regression analysis was
      applied. Compared with the line of identity, there was no statistical difference
      between slopes of left ventricular geometry and RV geometry, but conductance was
      highly dependent upon temperature. This was reflected in rho, the resistivity of
      saline. Rho varied from 80 to 51 (omega-cm) while temperature varied from 8 to 38
      degrees C (p < 0.01). These observations suggest that conductance may be useful
      for measuring right as well as left ventricular volumes. During changes in blood
      temperature, multiple measurements of rho, in appropriately drawn blood samples,
      are necessary to maintain accuracy.

PMID- 8573891
TI  - Flow distributions in hollow fiber hemodialyzers using magnetic resonance Fourier
      velocity imaging.
AB  - Distribution of flow within the hollow fibers and the dialysate compartment of
      hemodialyzers is difficult to measure; previous work has suggested that flow
      distributions may be non uniform. Magnetic resonance Fourier velocity imaging was
      used to determine flow distributions within the hollow fibers and dialysate
      compartment of three commercial hemodialyzers (CA170, CT190, and F60A). Distilled
      water was pumped without pulsatility through the hollow fibers and the outflow
      was circulated in a countercurrent direction through the dialysate compartment.
      Steady state flow distributions were determined simultaneously in both directions
      using input flow rates of 300 and 600 ml/min. Flow distributions within the
      hollow fibers were relatively uniform in most hemodialyzer cross sections,
      approximately Gaussian, and similar for all hemodialyzers. Flow distributions in
      the dialysate compartment were non uniform and skewed to high flow rates. High
      flow in the dialysate compartment was largely outside the fiber bundle for the
      CA170 and CT190 hemodialyzers. Local regions containing both low flow within the
      hollow fibers and high flow in the dialysate compartment were observed for the
      F60A hemodialyzer, and these regions became more prominent at a flow rate of 600
      ml/min. The results of this study demonstrate that flow distributions within the
      hollow fibers and dialysate compartment of hemodialyzers can be simultaneously
      determined using magnetic resonance Fourier velocity imaging. It is concluded
      that the distribution of flow within the hollow fibers of hemodialyzers is
      relatively uniform but in the dialysate compartment it is not uniform and depends
      upon hemodialyzer design.

PMID- 8573892
TI  - Determination of fluid shifts during chronic hemodialysis using bioimpedance
      spectroscopy and an in-line hematocrit monitor.
AB  - Effective ultrafiltration in hemodialysis requires a plasma refilling rate (PRR)
      sufficient to support blood volume. Knowledge of PRR and compartment shifts helps
      in understanding intradialytic events and may improve fluid removal. Simultaneous
      measurements with in-line hematocrit and bioimpedance spectroscopy were done in
      eight patients (17 runs) and extended for 15-60 min beyond the end of
      hemodialysis to determine fluid shifts and evaluate the relationship between
      changes in blood volume, extracellular fluid volume, and PRR. Absolute blood
      volumes, plasma refilling rates, and interstitial fluid volumes were calculated.
      Significant correlations were noted between different compartment volumes and the
      change in weight and estimates of plasma refilling. Pooling all runs, the change
      in interstitial fluid volume from beginning to end of hemodialysis correlated
      with the change in weight (r = 0.63, p = 0.01). Changes in PRR tracked changes in
      interstitial fluid volume for patients with two or more runs. In conclusion, the
      combination of in-line hematocrit and bioimpedance spectroscopy allows the
      quantification of different compartment volumes and PRR. Interstitial fluid
      volume may be a major determinant of PRR. This information would permit the
      development of strategies to reduce intradialytic morbidity.

PMID- 8573893
TI  - Treatment of secondary hyperparathyroidism with low dose intermittent calcitriol
      in hemodialysis patients. Imaging and cost analysis.
AB  - Calcitriol therapy is effective in the treatment of secondary hyperparathyroidism
      both during intravenous and oral administration, but there are doubts about the
      length of therapy and the duration of results. There are conflicting reports
      about results in size and activity of enlarged glands studied by ultrasound and
      double-tracer-subtraction-scintigraphy (DTSS). In 12 patients, 1 microgram of
      calcitriol was administered three times a week, intravenously and orally in
      alternate modes, for 46 weeks (therapy period) and orally for 46 weeks (follow-up
      period). During therapy, parathyroid hormone levels decreased in all patients,
      and in eight decreased by about 50% and were maintained at low levels during
      follow-up in five patients. Nine enlarged glands were detected by ultrasonography
      at the start of the study, and four hotspots were detected by DTSS;
      ultrasonography and DTSS were repeated at the end of the therapy and at the end
      of the follow-up: ultrasonography did not yield any significant variation in
      size, while one hot spot disappeared on DTSS. Basing their judgment on the lower
      cost of oral rather than intravenous administration, and on the good results of
      oral therapy, the authors stress the advisability of taking into account clinical
      and financial considerations before choosing the route of administration.

PMID- 8573894
TI  - Once weekly intravenous calcitriol suppresses hyperparathyroidism in hemodialysis
      patients.
AB  - Although thrice weekly intravenous calcitriol therapy suppresses parathyroid
      hormone in end-stage renal disease patients, the efficacy of once weekly
      administration is not known. Sixty-three patients hemodialyzed for a mean
      duration of 44 +/- 4 months were treated with once weekly intravenous calcitriol
      at a mean dose of 2.8 +/- 1 microgram/week. Parathyroid hormone was significantly
      suppressed from a mean baseline level of 471 +/- 38 to 342 +/- 46 at 5 months and
      220 +/- 40 pg/ml at 7 months of therapy. Plasma calcium levels rose from 9.0 +/-
      0.1 to 9.4 +/- 0.1 and 9.9 +/- 0.2 mg/dl, respectively. Plasma phosphate level
      was unchanged. No untoward side effects were observed. The same mean dose of
      calcitriol achieved a comparable degree of parathyroid hormone suppression
      regardless of whether patients were on prior thrice weekly or no prior therapy.
      In patients who had been treated with thrice weekly bolus injections, switching
      to a once weekly bolus injection achieved a comparable suppression with a 36%
      reduction in the cumulative dose. Thus, once weekly intravenous bolus
      administration of calcitriol resulted in a rapid and marked suppression of
      parathyroid hormone, similar in adequacy to thrice weekly boluses but at a
      considerably lower cumulative weekly dose. Results were particularly impressive
      in patients recently starting dialysis, suggesting that once weekly
      administration is safe, cost effective, and should become standard therapy.

PMID- 8573895
TI  - Gastrointestinal complications after renal transplantation. 10 Year data from a
      North Indian Transplant Center.
AB  - Gastrointestinal complications are responsible for substantial morbidity and
      mortality among renal allograft recipients in developing countries. During a 10
      year period, 166 (62.6%) of 265 allograft recipients developed gastrointestinal
      complications. This figure reflects the high incidence of infectious
      complications, especially acute diarrheas. Also notable was the incidence of
      esophageal candidiasis (7.2%), ischemic colitis (2.6%), and gastrointestinal and
      peritoneal tuberculosis (3.0%). Almost one quarter of the complications developed
      in the first 6 months after transplantation. Mortality was the highest with acute
      ischemic colitis (100%), pancreatitis (60%), and upper gastrointestinal
      hemorrhage (40%). Improvements in standards of living and sanitary conditions,
      pre transplant evaluation and assessment of risk factors, prophylaxis with anti
      ulcer drugs, early diagnosis, and appropriate treatment are needed to decrease
      the frequency and severity of gastrointestinal complications in renal allograft
      recipients.

PMID- 8573896
TI  - Does cholestyramine interfere with cyclosporine absorption? A prospective study
      in renal transplant patients.
AB  - Increased cardiovascular deaths have been reported in long-term survivors after
      renal transplantation. In the primary and secondary coronary prevention trials,
      reduction of elevated cholesterol has been demonstrated to decrease the incidence
      of cardiovascular events. The authors previously reported that only 33% of renal
      transplant patients achieved the National Cholesterol Education Program Expert
      Panel target values of total and low density lipoprotein cholesterol with niacin
      > or = 2 g/day or lovastatin 40 mg/day. Indeed, combination therapy with the bile
      acid sequestrant, cholestyramine appears to be a logical choice. Hence, the
      pharmacokinetics of cyclosporine were studies before (baseline, on day 1) and
      after starting cholestyramine 4 g/day, given as a single dose at noon (study
      repeated on day 4) in six nondiabetic renal transplant patients. Included were 1
      woman and 5 men; their mean age (+/- SEM) was 45 +/- 6 years, and they were all >
      1 year post transplantation. These patients were receiving cyclosporine,
      azathioprine, and prednisone based maintenance immunosuppression. Compared to day
      1 (baseline period), the peak (644 +/- 142 ng/ml versus 625 +/- 168 ng/ml; ns)
      and trough (196 +/- 17 ng/ml versus 214 +/- 32 ng/ml; ns) cyclosporine levels and
      the time to peak (2 hr versus 2 hr) were not significantly different on day 4
      (post cholestyramine period) of the study. Furthermore, the area under the curve
      (3721 +/- 586 ng/hour/ml versus 4143 +/- 778 ng/hour/ml; ns) was not
      significantly different. Our data suggest that cholestyramine 4 g, given once a
      day at noon, did not interfere with the absorption of oral cyclosporine. Hence,
      combination therapy with cholestyramine appears to be a reasonable choice in
      renal transplant patients with resistant hypercholesterolemia.

PMID- 8573897
TI  - Increased soluble CD14 levels in patients on hemodialysis. Influence of dialysate
      endotoxin or incompatibility to dialyzer membranes?

PMID- 8573898
TI  - Bioincompatible membranes place patients with acute renal failure at increased
      risk of infection.
AB  - The mortality of critically ill patients with acute renal failure (ARF) requiring
      hemodialysis remains high (> 50%), even though major improvements in the
      management of this disorder have been made. Sepsis has been identified as a major
      cause of death in ARF. Experimental data have suggested that bioincompatible
      membranes aggravate uremia induced neutrophil dysfunction. In the following two
      combined prospective, randomized, clinical studies, the effects of the
      biocompatibility of dialysis membranes on the susceptibility to infection were
      compared in 72 surgical and medical patients with ARF. The group of patients
      treated with biocompatible polyacrylonitrile membranes had a significantly lower
      incidence of bacterial infections and a lower relative and absolute mortality
      rate due to sepsis, compared to patients treated with bioincompatible cuprophane
      membranes. These investigations identified bioincompatibility as a factor that
      adversely affects the prognosis of critically ill patients with ARF.

PMID- 8573899
TI  - The effect of dialyzer membrane and etiology of kidney disease on the
      preservation of residual renal function in chronic hemodialysis patients.
AB  - It is commonly believed that renal function rapidly decreases in the vast
      majority of chronic hemodialysis patients. Three hundred thirty-four patients
      starting chronic hemodialysis between 1/1/88 and 12/31/92 at six hemodialysis
      units were prospectively studied. Renal function was determined every 3 months by
      68 hr urine collection expressed as weekly fraction urea clearance (L/L total
      body water/wk). glomerular filtration rate was calculated from the mean of the
      urea and creatinine clearance. After 3 years, glomerular filtration rate exceeded
      4 ml/min in 14% of patients. For a thrice weekly dialysis schedule, it was
      assumed that a weekly fractional urea clearance of 3 L/L/wk is equal to a
      dialysis KT/V of 1 and patients need a minimum KT/V of 1.2 per treatment. After 3
      years of chronic hemodialysis therapy, residual renal function was found to
      provide 15% of the dialysis requirement in 19% of patients and 30% of the
      dialysis requirements in 9% of patients. The occasional patient maintains
      sufficient residual renal function to provide over 40% of the dialysis
      requirement for over 4 years. In a retrospective analysis, patients treated only
      with Cupraphan membrane had a more rapid loss of renal function compared to those
      never treated with Cupraphan (Besnberg Corp., Germany). The majority of patients
      with polycystic kidney disease maintained a glomerular filtration rate greater
      than 2 ml/min for 4 years or longer.

PMID- 8573900
TI  - Efficacy of different hepatitis B vaccination strategies in patients receiving
      hemodialysis.
AB  - Patients with end-stage renal disease have an impaired immune response to
      vaccination against Hepatitis B. The efficacy of different vaccines and vaccine
      schedules was studied in a group of patients receiving long-term hemodialysis.
      All patients received an initial 6 month course of intramuscular vaccine with
      either three doses of Recombivax (48 patients) or four doses of Engerix B (50
      patients). This was successful in 71% and 74% of patients, respectively. In 10
      patients unresponsive to 4 doses of Engerix B, a second course (2-4 doses) was
      successful in 5, thus increasing the overall success rate to 84%. Repetitive
      doses of vaccine intradermally were used as an alternative approach in eight
      patients who were unresponsive to intramuscular vaccination resulting in
      seroconversion in six. Finally, booster doses of intramuscular Engerix B have
      been used in 26 patients who lost their antibodies after successful vaccination.

PMID- 8573901
TI  - Overestimation of hemodialysis dose depends on dialysis efficiency by regional
      blood flow but not by conventional two pool urea kinetic analysis.
AB  - In 26 patients, a linear relationship between delta Kt/V (equilibrated minus
      single pool) and dialysis efficiency K/V was noted (r = -0.72). To determine if
      such a relationship would be supported by formal urea kinetic analysis, t, Kd,
      and V were randomly varied in 1,400 simulations using both
      intracellular/extracellular and regional blood flow 2 pool variable volume
      models. In the intracellular/extracellular model, delta Kt/V was best correlated
      with Kd/Kc (r = -0.96), where Kc is the intercompartmental clearance. Kc was not
      correlated with V, which translated into a lack of correlation between delta Kt/V
      and V, and a better correlation between delta Kt/V and Kd than between delta Kt/V
      and K/V. In the regional blood flow model delta Kt/V was best correlated with
      Kd/QL (r = -0.99), where QL is the perfusion of the low flow compartment. QL was
      correlated with V because QL is a function of cardiac output, which varies with
      surface area and therefore with V. In the regional blood flow model, delta Kt/V
      did correlate with V (r = 0.49), and better with K/V (r = -0.76) than with K (r =
      -0.47), similar to the results in patients. The slope of delta Kt/V on K/V
      depended upon fQL (the fractional perfusion of the low flow compartment) and on
      cardiac index. At an fQL of 0.15 and a cardiac index of 2.85, the theoretical
      slope was similar to that seen in observational data: delta Kt/V = -0.6 x K/V +
      0.03. The results show that the regional blood flow model predicts the observed
      relation between delta Kt/V and K/V, whereas the intracellular/extracellular
      model fails in this task unless one arbitrarily ties Kc to V.

PMID- 8573902
TI  - Longitudinal assessment of body composition in CAPD patients using bioelectric
      impedance analysis. A comparison with hemodialysis patients.
AB  - The utility of bioelectric impedance analysis was assessed for longitudinal
      evaluation of body composition in two groups of uremic patients, one on CAPD and
      one on hemodialysis treatment, with no clinical marks of hyperhydration or
      infection. Nineteen CAPD patients (11 men 8 women) and 21 HD patients (12 men 9
      women) were studied with bioelectric impedance analysis for a period of 12
      months; total body water, fat free mass, and fat mass were calculated from
      bioelectric impedance analysis data of resistance and reactance at time 0 and 12
      months later. No significant differences in body composition were found in the
      two groups at time 0 and 12 months later, with a similar trend for total body
      water, fat free mass, and fat mass. In CAPD, a significant increase in body
      weight was observed due mainly to a rise in fat mass, particularly evident in
      women with uremia. Bioelectric impedance analysis appears to be an instrument
      easily repeatable and reliable in CAPD and HD patients, reflecting at the same
      time body composition, the dialytic adequacy of a technique, and the patient's
      well being.

PMID- 8573903
TI  - A Corethane/polyester composite vascular prosthesis for vascular access.
      Comparison with expanded polytetrafluoroethylene grafts in a canine model.
AB  - An important need in hemodialysis is a self-sealing prosthesis for vascular
      access with at least equivalent patency and biostability to expanded
      polytetrafluoroethylene (ePTFE) alternatives. The authors have developed a
      Corethane/polyester composite (CPC) graft with an inner blood interfacing layer
      of spun Corethane fibers (10-15 microns diameter; pore size 30-60 microns)
      impregnated with a gelatin-heparin complex and an outer soft tissue interfacing
      warp-knitted polyester sheath. Twenty-six CPC grafts (6 mm internal diameter; 25
      30 cm length) and eight Gore-Tex ePTFE grafts (same dimensions) were implanted as
      femoral artery-to-vein shunts in dogs on low dose (162 mg/day) aspirin, and
      subjected to weekly dialysis needle punctures for up to 52 weeks. Patency was 73%
      (19/26 with 15 at 52 weeks) for the CPC grafts and 63% (5/8 at 52 weeks) for the
      ePTFE controls, with more favorable healing (e.g., less extensive mural thrombi)
      of the CPC grafts. The hemostasis time per needle pair after removal (3.1 min
      mean for CPC versus 21.2 min mean for ePTFE) and the blood loss in achieving
      hemostasis (5.7 g mean for CPC versus 47.9 g for ePTFE) documented the
      significant (p < 0.0001) performance advantages of the CPC prosthesis.

PMID- 8573904
TI  - Healing characteristics of hybrid and conventional polytetrafluoroethylene
      vascular grafts.
AB  - The concepts of porosity and healing in vascular grafts are interrelated. The
      initial phase of healing includes cellular infiltration into the prosthesis
      followed by tissue ingrowth from perigraft sources. This provides a framework for
      development of a pseudointima. The microstructure of conventional expanded
      polytetrafluoroethylene grafts with an average internodal distance of 20 microns
      or less results in hindered cellular penetration and tissue ingrowth. A new
      microstructure hybrid polytetrafluoroethylene graft is described that has a high
      porosity 60 microns average internodal distance on the adventitial surface
      combined with a fine pore 20 microns average internodal distance on the luminal
      surface. In addition, tapered through-pore channels provide a direct channel from
      the adventitia and lumen that allow biologic communication to occur where cells
      and tissue can penetrate and vaginate. Canine carotid and femoral implant studies
      were performed to elucidate healing effects of polytetrafluoroethylene graft
      structure on cellular penetration and tissue ingrowth. Enhanced cellularity and
      tissue ingrowth were observed in hybrid polytetrafluoroethylene implants compared
      to implants of conventional expanded polytetrafluoroethylene. Human explants also
      demonstrate enhanced initial cellular penetration and capillary formation in the
      hybrid polytetrafluoroethylene graft wall. It is postulated that hybrid
      polytetrafluoroethylene will result in improved clinical performance as a result
      of removal of the healing restrictions associated with random microstructure
      conventional expanded polytetrafluoroethylene vascular grafts.

PMID- 8573905
TI  - Novel method to measure access flow during hemodialysis by ultrasound velocity
      dilution technique.
AB  - This article presents the theory and bench validation of access flow measurement
      by ultrasound velocity dilution. Reversal of dialysis lines creates a zone of
      mixing in the vascular access, allowing the use of dilution technique for access
      flow measurement. The method of sound velocity dilution sensor calibration was
      analyzed. A single sensor system was investigated for blood circulation and
      isothermal injections. A dual sensor system was investigated with heated
      hypertonic saline circulation for both body temperature (isothermal) and room
      temperature (cold) injections. The accuracy of in vitro access flow measurement
      was studied on a two pump bench model, dialysis line flow was varied from 200 to
      400 ml/min, access flow was varied from 300 to 2500 ml/min. For the dual sensor
      system, dilution access measurements tracked a gravimetrically calibrated in-line
      flow sensor within 3.25 +/- 0.34% for isothermal injections, and within 5.81 +/-
      0.43% for cold injections. Measurements were repeatable within 3% independent of
      the temperature of the injected saline. For the single sensor system, results
      tracked the in-line flow sensor within 3.83 +/- 0.79%. These data show that
      access flow can be accurately measured by sound velocity dilution technique.

PMID- 8573906
TI  - Clinical measurement of blood flow in hemodialysis access fistulae and grafts by
      ultrasound dilution.
AB  - Blood flow is a fundamental property of the hemodialysis access device. Periodic
      monitoring of flow could be useful for detection of impending access failure and
      prevention of underdialysis, but simple measurements of access flow during
      hemodialysis are not currently available. Flow in peripheral arteriovenous
      fistulas and grafts was examined using an indicator dilution technique while the
      patient's blood lines were reversed. The indicator was a bolus of normal saline
      detected by an ultrasound flow sensor clamped onto the patient's blood line. The
      ultrasound sensor measured blood flow in the tubing using an established transit
      time method and simultaneously detected saline dilution of the blood from changes
      in the average cross sectional velocity of an ultrasound beam that illuminated
      the blood flowing through the tubing. Access flow was measured 110 times in 25
      patients, 16 with loop grafts and 9 with native fistulas. Measured access flow
      ranged from 125 to 2860 ml/min. The mean error of duplicate measurements within
      patients was 5.0 +/- 3.8%. To assess the adequacy of saline mixing with the
      blood, access flow was measured at three dialyzer blood flow rates. In paired
      studies, no significant difference was observed in access flow measured at two
      lower dialyzer blood flow rates when compared to flow measured at 350 ml/min. A
      comparison with access flow measured by a duplex color Doppler technique in seven
      patients gave a mean error of 9.2 +/- 7.2% in paired studies. These data show
      that blood flow in peripheral arteriovenous grafts and fistulas can be measured
      accurately during hemodialysis using ultrasound velocity dilution.

PMID- 8573907
TI  - Hemodialysis access recirculation measured by ultrasound dilution.
AB  - The most widely used clinical method for measuring recirculation in the access
      device is based on urea dilution. The three simultaneous blood samples required
      during hemodialysis interrupt the treatment, and results of chemical analysis are
      often delayed for several days. Alternatively, detecting recirculation by
      dilution of arterial blood caused by a bolus of normal saline injected into the
      venous blood line has several advantages. In this study, an ultrasound sensor
      clamped onto the arterial line entering the dialyzer was used to detect such
      dilution from a reduction in sound velocity observed in the saline diluted blood.
      Within the target range, the change in ultrasound velocity (ultrasound dilution)
      is linearly correlated with the dilution of whole blood by normal saline. The
      same sensor was also used to measure flow in the blood line using an established
      ultrasound transit-time method. During 34 hemodialyses in 28 patients, only 3
      patients had detectable recirculation measured by ultrasound dilution. To further
      evaluate the sensitivity of the new method the dialysis lines were reversed
      during hemodialysis in the 25 patients with no recirculation. After this, all had
      detectable recirculation ranging from 10 to 60%. The mean error of duplicate
      measurements was 3.9 +/- 2.8%. Recirculation by ultrasound dilution correlated
      closely with recirculation measured by urea dilution (r = 0.9156, p < 001). The
      data suggest that the ultrasound dilution method is both sensitive and accurate.
      Ease of use and immediate availability of results added to the clinical
      usefulness of this method for evaluating the integrity of the hemodialysis
      access.

PMID- 8573908
TI  - The effect of anterior chordal replacement on mitral valve function and stresses.
      A finite element study.
AB  - During the past 10 years chordal replacement with expanded
      polytetrafluoroethylene (ePTFE) suture has become an acceptable mitral valve
      repair technique. Unfortunately, its effect on the mechanical function of the
      valve is unclear. The purpose of this study was to test whether replacement of
      ruptured anterior leaflet chordae with ePTFE suture restores mitral valve
      function and stresses to normal ranges. To answer this question, the authors'
      existing finite element model of the mitral valve was modified to simulate six
      different valve conditions: 1) normal, 2) rupture of anterior chordae, 3)
      replacement using two 4-0 ePTFE sutures, 4) replacement using four 4-0 ePTFE
      sutures, 5) replacement using two 5-0 ePTFE sutures, and 6) replacement using
      four 5-0 ePTFE sutures. Physiologic pressures representing ventricular systole
      from the onset of isovolumic contraction to peak left ventricular pressure were
      applied to each model. It was found that after rupture, coaptation was impaired
      and stresses increased dramatically in chordae adjacent to the rupture site.
      Replacement with two ePTFE sutures restored proper coaptation and lowered
      stresses to near normal. Using four sutures also restored coaptation and lowered
      stresses even further. There was minimal difference between 4-0 and 5-0 suture.
      In conclusion, the replacement of ruptured anterior leaflet chordae with ePTFE
      suture restores both mitral valve function and stresses to normal ranges.

PMID- 8573909
TI  - Ventricular pressure slope and bileaflet mechanical heart valve closure.
AB  - The maximum left ventricular pressure slope (dP/dt) value has been used by
      several investigators as the criterion for studying mitral valve closure. In this
      article, the relationship between the ventricular pressure slope (dP/dt) and the
      leaflet closing behavior of bileaflet mechanical heart valves (BMV) is
      investigated. Two current BMVs, the St. Jude Medical 29 mm and CarboMedics 29 mm,
      installed in the mitral position of a mock circulatory pulsatile flow loop were
      used as the study model. Under simulated physiologic pressures and flow
      conditions, the experiment was conducted at 70, 90, and 120 beats/min with
      corresponding flow rates of 5.0, 6.0, and 7.5 liters/min, respectively. A laser
      sweeping technique was used to monitor the leaflet closing motion within the last
      3 degrees excursion at valve closure. A modified dual beam laser sweeping
      technique system was used to register the difference of leaflet/housing impact
      time between the two BMV closing leaflets in asynchronous closure. Common BMV
      asynchronous closures were found in both BMVs at all three heart rates tested.
      The second closing leaflet was found to always close at higher velocity than the
      first. Simultaneous measurements of the ventricular pressure (Pv) and the leaflet
      closing time showed that Pv exhibited three stage characteristics. In the first
      stage, Pv gradually increased as the ventricle was filled. A sudden rise of Pv
      occurred immediately after closing of the first leaflet. The maximum dp/dt
      occurred in the third stage after closure of both BMV leaflets. The BMV closing
      behavior and the corresponding Pv pattern were found to depend strongly upon
      valve type and heart rate. The time averaged ventricular pressure slope (dp/dt)
      values at 70, 90, and 120 beats/min were about 40, 70, and 150 mmHg/sec for the
      St. Jude Medical valve and 40, 105, and 205 for the CarboMedics valve during the
      first closing stage. The maximum dp/dt values were 2670, 4350, and 5000 mmHg/sec
      for the St. Jude Medical valve and 1210, 2530, and 3210 mmHg/sec for the
      CarboMedics valve at the three heart rates tested, respectively. The study showed
      that the left ventricular pressure patterns (dP/dt) at valve closure were the
      result of valve operation under given driving conditions. The dp/dtmax cannot be
      used as the criterion for studying BMV closure.

PMID- 8573910
TI  - Power of the fatigue resistant in situ latissimus dorsi muscle.
AB  - To evaluate the in situ latissimus dorsi muscle as an actuator for circulatory
      assistance, 1) muscle power was analyzed in animal experiments, and 2) muscle
      weight was measured in human cadavers. Three adult goats underwent 12 week
      preconditioning. The insertion of the latissimus dorsi muscle was then connected
      to a spring and a tension transducer in series. The stroke length was measured
      with a photosensor without power loss. With contraction of muscles under various
      loads, tension-length relationships at end contraction and end relaxation were
      obtained and the maximum area of a square drawn within both lines was assumed to
      be maximum external power. Good fatigue resistance and the highest maximum
      external power of 3.16 Watts/kg at 120 min was derived from preconditioned
      latissimus dorsi muscle in burst frequency of 50 Hz. Muscle weight in 42 human
      cadavers was negatively correlated with age (r = 0.56) and was expected to be
      221.6 g in patients aged 45 years. According to these data, the power of a human
      preconditioned latissimus dorsi muscle was estimated as 0.7 Watts. It was
      concluded the power of in situ preconditioned latissimus dorsi muscles was
      appropriate for right heart assistance or counterpulsation for left heart assist.

PMID- 8573911
TI  - An approach to reducing hemolysis in an axial-flow blood pump.
AB  - In an attempt to decrease hemolysis caused by an axial-flow blood pump, we
      studied whether specific speed (Ns) at a design point (determined by flow in
      m3/min, pump head in m, and pump speeds in rpm), should be kept within the
      existing engineering standard range (1000 < Ns < 2500) or whether pump speed
      should be reduced to a minimum (Ns < 1000). Four pumps (A: 14,000 rpm, B: 18,000
      rpm, C: 22,000 rpm, and D: 26,000 rpm), each with an impeller 11.8 mm in
      diameter, were designed to accommodate a flow rate of 5 L/min and a pressure head
      of 100 mmHg. At this design point, the Ns of each pump was calculated as A:758,
      B:974, C:1191, and D:1407. Pump performance was observed, and the total
      efficiency of each pump was calculated. The hemolysis index (HI) was calculated
      after simultaneous testing in duplicate of all four pumps using fresh goat blood
      (anticoagulated with citrate-dextrose solution) in a closed mock-loop circuit.
      Total efficiency of each pump was calculated as A:49%, B:50%, C:45%, and D:22%.
      In the first hemolytic test, HIs were measured as A:0.066, B:0.18, and C:0.13; a
      water seal failed in pump D. In the second test, HIs were B:0.077, C:0.0499, and
      D:0.12; a bearing failed in pump A. It is concluded that a lower level of
      hemolysis is associated with a pump speed in the minimum range at the design
      point, even though Ns is outside the standard range.

PMID- 8573912
TI  - Proinflammatory cytokine levels in patients undergoing cardiopulmonary bypass.
      Does lung reperfusion influence the release of cytokines?
AB  - Proinflammatory cytokines have been implicated in mediating tissue injury after
      cardiopulmonary bypass. Causative factors of inflammatory response after
      cardiopulmonary bypass include contact of the blood with the extracorporeal
      circuit and heart-lung reperfusion injury when discontinuing bypass. To evaluate
      proinflammatory cytokine release during cardiopulmonary bypass, plasma levels of
      interleukin-6, 8, and monocyte chemoattractant factor were measured in the radial
      artery (for systemic blood) and left atrium before and after cardiopulmonary
      bypass. A total of 13 patients were studied, with no deaths or complications. In
      both radial artery and left atrium, interleukin-6, 8, and monocyte
      chemoattractant factor rose significantly after cardiopulmonary bypass (p < 0.05
      versus before cardiopulmonary bypass). These changes may have been caused by
      removal of the aortic cross clamp and recommencement of artificial ventilation,
      which result in reperfusion of the pulmonary capillary beds. There were no
      differences in cytokine levels after cardiopulmonary bypass in the radial artery
      and left atrium. This result suggested that lung reperfusion injury after
      cardiopulmonary bypass may not be the major causative factor of the release of
      proinflammatory cytokines.

PMID- 8573913
TI  - Ideal anticoagulation for use with a left ventricular assist device.
AB  - To establish ideal anticoagulation therapy for use with a left ventricular assist
      device, a study was done administering various anticoagulants: heparin,
      argatroban, a prostacyclin analogue combined with a protease inhibitor, or a
      protease inhibitor alone. Cardiac asisting by LVAD without any anticoagulants
      results in marked activation of blood coagulation or fibrinolysis. Administration
      of argatroban, as well as heparin, produces a bleeding tendency. Administration
      of a protease inhibitor (nafamostat mesilate, FUT-175) as a sole anticoagulant
      induces activation of the blood coagulation system to some extent, but it is
      within acceptable limits. Combined administration of a prostacyclin analogue (PG)
      and FUT-175 is most effective in maintaining balanced blood coagulation and
      fibrinolysis.

PMID- 8573914
TI  - Hemostatic profiles of HeartMate ventricular assist device recipients.
AB  - Candidates for ventricular assist devices often have hepatic dysfunction and
      concomitant coagulation abnormalities. Factors II, V, VII, XI, plasminogen,
      fibrinopeptide A (FpA), and D-dimers were measured in 19 HeartMate
      (ThermoCardiosystems, Inc., Woburn, MA) patients before device implantation; at 6
      hr, 24 hr, and 2 weeks postimplantation; and before explantation. Ten patients
      had entry hepatic dysfunction (total bilirubin > 2 mg/dl; aspartate and alanine
      aminotransferases > 60 U/L); nine had normal hepatic function. All except one
      patient received perioperative aprotinin; all received only aspirin and
      dipyridamole after surgery. At preimplant, both patient groups had subnormal
      factor II, V, VII, XI, and plasminogen with elevated FpA and D-dimer. By 2 weeks
      postimplant, these factor levels had normalized, except for FpA and D-dimer
      levels, which suggest ongoing remodeling of fibrin deposits on the device
      surfaces. No statistically significant differences in the assayed hemostatic
      markers were observed between the two patient groups. Clinically, 15/19 (79%)
      patients survived to cardiac transplantation; 3/19 (16%) patients required
      reoperation for early bleeding. All three had low factor VII and XI; two of three
      also had hepatic dysfunction and subnormal levels of factor II and V. Most
      patients with entry hepatic dysfunction improve after device implantation; all
      four deaths were in patients with persistent hepatic dysfunction despite
      circulatory support.

PMID- 8573915
TI  - Danger of urokinase as an anticoagulant with left ventricular assist devices.
AB  - The sole administration of urokinase causes no initial prolongation of activated
      partial thromboplastin time (A-PTT), but thereafter produces serious progressive
      prolongation of A-PTT; it also causes a progressive, severe decrease in
      fibrinogen levels and alpha 2-plasmin inhibitor activity by depletion. The
      antithrombogenicity of urokinase is not caused by prevention of blood coagulation
      system activation by antithrombin effect, but by secondary fibrinolysis by
      plasmin. Consequently, the administration of urokinase as a sole anticoagulant
      results in activation of coagulation and fibrinolysis, and, as a result, induces
      disseminated intravascular coagulation. Therefore, it is concluded that
      administration of urokinase is an inadequate anticoagulation therapy unless it is
      combined with other antithrombin agents.

PMID- 8573916
TI  - Pathophysiologic role of contact activation in bleeding followed by
      thromboembolic complications after implantation of a ventricular assist device.
AB  - The time period after implantation of a ventricular assist device in patients
      with end-stage heart disease is complicated by hemorrhage in the early
      postoperative period and by thromboembolism in the later course. To investigate
      the pathophysiologic role of contact activation in 12 bridging patients (10
      patients with a paracorporeal Berlin Heart [Berlin Heart GmbH, Berlin, Germany],
      2 patients with an intracorporeal Novacor system [Novacor N100; Baxter, Oakland,
      CA]), hemostatic parameters were determined until heart transplantation or at
      least up to the 51st postoperative day. The following were observed: 1) In the
      early postoperative period, until day 15, levels of contact factors XI, XII, and
      prekallikrein were below normal, whereas levels of plasmin-a2-antiplasmin (PAP)
      complexes were elevated. Thrombin-antithrombin III (TAT) complexes, as well as
      platelet factor 4 and beta-thromboglobulin, significantly increased immediately
      after surgery. 2) In the later postoperative period, starting with the third
      postoperative week, an increase of factors XI, XII, and prekallikrein was
      observed. PAP and TAT complexes, as well as platelet factor 4 and beta
      thromboglobulin, remained elevated. It is concluded that, in the early
      postoperative period, hemostasis is influenced mainly by an activation of the
      intrinsic contact system dependent fibrinolytic system with consumption of
      contact factors and increased levels of PAP complexes, whereas later system
      dependent fibrinolysis becomes less important, leading to a shift of the balance
      toward coagulation, with sustained prothrombin and platelet activation. This is
      in accord with the observed clinical complications (e.g., early postoperative
      bleeding, and thromboembolic events later on).

PMID- 8573917
TI  - Abbreviated two sample, single pool, variable volume urea kinetic modeling.
AB  - A two-point model has been developed that uses actual predialysis (C0) and
      postdialysis (C1) blood urea nitrogen (BUN) values, and calculates the third
      value (C2) by forcing a solution for urea generation (Gurea) and urea volume of
      distribution (Vurea) that results in a predialysis BUN value a week later (C7)
      similar to C0. This two-point model was evaluated in 64 patients (mean age: 59 +/
      17 years) undergoing thrice weekly chronic hemodialysis, with mean predialysis
      (C0) and postdialysis (C1) midweek BUN values of 70 +/- 16 and 28 +/- 10 mg/dl,
      respectively. Compared to the standard three-point, single pool, variable volume
      standard, the two-point model accurately predicted Kt/V (1.08 +/- 0.22 versus
      1.08 +/- 0.23, respectively) and Vurea (48.1 +/- 14.1 versus 48.1 +/- 13.9 L,
      respectively). The model also approximated C2 concentrations within an 11% range
      (66 +/- 20 versus 69 +/- 16 mg/dl for modeled and actual, respectively; p =
      0.007) that allowed useful estimates of Gurea (6.64 +/- 1.87 versus 6.71 +/- 2.47
      g/min for model and actual, respectively) and normalized protein catabolic rate
      (0.94 +/- 0.19 versus 0.94 +/- 0.26 for modeled and actual, respectively; p =
      ns). It is concluded that the two-point model described may be used for
      calculation of Kt/V and normalized protein catabolic rate in the clinical setting
      when a third BUN value is not available.

PMID- 8573919
TI  - Correlation between urea reduction rates and serum albumin levels in patients on
      hemodialysis.
AB  - Monthly urea reduction rates and serum albumin levels were measured in 12
      dialysis patients during a year when standard hemodialysis was replaced by high
      efficiency hemodialysis without changing treatment duration. Initially, mean urea
      reduction rates were 57-58% and mean serum albumin levels were 3.6-3.7 g/dl.
      Introduction of high efficiency hemodialysis gradually increased mean urea
      reduction rates to 68-70% (an increase in dialysis delivery of 40%). There was a
      parallel increase in mean albumin levels by 0.5 g/dl to 4.1-4.2 g/dl two months
      after the rise in urea reduction rate. Increased insulin administration was
      necessary to compensate for probable increased caloric intake in diabetic
      patients. Hemodialysis patients achieve improvement in nutritional status after
      dialysis delivery is increased using high efficiency hemodialysis without
      decreasing treatment duration.

PMID- 8573918
TI  - Comparison of a modified urea kinetic model direct dialysis quantification and
      classic urea kinetic modeling.
AB  - In the classic urea kinetic model (UkM), the measurement of clearance (K) as a
      model input is onerous, and its result is higher than actual body clearance
      because of urea disequilibrium. Urea kinetics performed by direct dialysis
      quantification (DDQ), with an equilibrated post rebound sample, gives reliable
      results but is routinely impractical. The modified UKM (mUKM) method is based on
      the input of urea distribution volume (V), easily obtainable by several methods
      and more stable than clearance, and uses simple formulae derived from urea mass
      balance, avoiding iterative computation. Compared with DDQ, mUKM results are
      identical, provided that the V value obtained by DDQ is used as input. Compared
      with UKM, mUKM urea clearances are significantly lower (158.1 +/- 20.5 versus
      180.7 +/- 26.8 ml/min), as are urea nitrogen generation rates (5.85 +/- 2.0
      versus 6.41 +/- 2.14 mg/min), whereas V results are close (32,444 +/- 6301 versus
      32,141 +/- 5293 ml): consequently, mUKM Kt/V is significantly lower than UKM Kt/V
      (1.07 +/- 0.17 versus 1.22 +/- 0.18). This is because both mUKM and DDQ take
      account of post dialysis urea rebound. Therefore, if UKM formulae are used with
      the DDQ body clearance and the equilibrated post rebound blood urea nitrogen
      value as input data, their results strictly approximate the reference DDQ (V =
      32,457 +/- 6274; Kt/V = 1.07 +/- 0.17; G = 5.85 +/- 2.0), demonstrating the
      common mathematical basis of DDQ and UKM. Therefore, reliable results may be
      obtained by DDQ, by mUKM, and by "equilibrated" UKM; we suggest that the mUKM
      model, less cumbersome than DDQ, and more reliable than UKM because it avoids the
      clearance measurement and the need for iterative computation, could be useful for
      routine kinetics.

PMID- 8573920
TI  - Does interleukin-1 induce hair loss?
AB  - Cytokines play an important role in both physiology and pathophysiology of human
      skin, and the possibility that they coordinate the cyclical hair growth cannot be
      excluded. Several clinical and experimental data point towards interleukin-1
      which might be a crucial inducer of hair loss in various hair disease. An
      aberrant expression of interleukin-1 beta was detected in affected areas of the
      scalp in alopecia areata. On the other hand, interleukin-1 has been shown to be a
      potent inhibitor of human hair growth in vitro. Mice showing an overexpression of
      the interleukin-1 alpha gene develop patchy hair loss. Taking all of the
      presently available data together, we hypothesize that interleukin-1 is a crucial
      mediator inducing cessation of hair growth.

PMID- 8573921
TI  - The concept of the acid mantle of the skin: its relevance for the choice of skin
      cleansers.
AB  - Whereas soap has long been the only cleansing agent, a new generation of
      cleansers, the so-called synthetic detergents or syndets, has been developed
      during the last decades. They offer a wide variety of formulations and are
      therefore becoming more and more important for cleansing of diseased and healthy
      skin. Among the syndets, especially those with a pH of about 5.5 seem to be
      relevant. In contrast to alkaline soap, they do not interfere with the cutaneous
      microflora, whose composition is linked to the skin surface pH. As their
      irritancy potential might be even lower than that of soap, the benefit-to-risk
      ratio of syndets appears favorable.

PMID- 8573922
TI  - Involvement of basic fibroblast growth factor in fibroblast-stimulatory serum
      activity of a patient with systemic lupus erythematosus and multiple
      dermatofibromas.
AB  - BACKGROUND: Multiple dermatofibromas (DFs) are often associated with systemic
      lupus erythematosus (SLE). An increased number of mast cells is observed in the
      upper portion or over the lesion of DF. OBJECTIVE: To investigate the role of the
      serum of a patient with multiple DFs, we examined its growth effects on
      fibroblasts. METHOD: 3H-Thymidine incorporation was used to examine the effects
      of the serum of an SLE patient with multiple DFs on fibroblasts derived from DF
      and normal skin. RESULTS: The serum of the SLE patient with multiple DFs
      exhibited a stronger growth-stimulatory activity on normal and DF-derived
      fibroblasts in a dose-dependent manner, compared to that of SLE without DFs or
      normal sera. The growth effects were inhibited in 40% by antiplatelet-derived
      growth-factor antibody and almost completely inhibited by antibody against basic
      fibroblast growth factor. Cultured fibroblasts derived from the upper portion of
      the DF lesion, which included most of the numerous mast cells, demonstrated a
      higher level of 3H-thymidine uptake after stimulation of autologous serum
      compared to that from the mid and lower portions of DF. CONCLUSION: These results
      suggested the existence of various fibroblast growth factors derived from the
      mast cells in SLE patients with multiple DFs.

PMID- 8573923
TI  - Detection of action, inhibition and augmentation spectra in solar urticaria.
AB  - BACKGROUND: The action spectrum of solar urticaria varies among cases. In
      addition, light spectra outside the activating wavelengths can influence the
      wheal formation in selected patients. OBJECTIVE: To know the mechanisms of light
      energy, we examined the effect of wavelengths on the skin and the serum factor.
      METHODS: The patient's skin and serum were exposed to artificial light sources,
      in vivo and in vitro, respectively. RESULTS: The action spectrum ranged from UVA
      to visible light (approximately 480 nm). The exposure to longer wavelengths
      immediately after the exposure inhibited the development of urticaria.
      Conversely, the irradiation of longer wavelengths before exposure increased the
      wheal formation. Furthermore, UVB irradiation prior to the exposure of urticaria
      eliciting light also increased the urticarial reaction, while postirradiation of
      UVB had no effect. The patient developed an urticarial wheal at the site of
      injection of her own serum, which had been previously exposed to the action
      spectrum in vitro. Preirradiation increased the production of the
      photosensitizer, while postirradiation revealed no effect. Ultrafiltration
      techniques showed that the molecular weight of the photosensitizer is more than
      300 kD. CONCLUSION: We detected action, inhibition and augmentation spectra in a
      patient with a severe solar urticaria. Various wavelengths influence the wheal
      forming factor in complex interactions.

PMID- 8573924
TI  - Primary cutis verticis gyrata or pachydermia verticis gyrata: a peculiar scalp
      disorder of mentally retarded adult males.
AB  - BACKGROUND: Primary or idiopathic cutis verticis gyrata (CVG) is often associated
      with mental retardation or chronic schizophrenia. OBJECTIVE: The aim of the
      present study was to evaluate the prevalence of primary CVG and its histological
      aspects in a psychiatric adult population. METHODS: Eighty-three hospitalized
      psychiatric adult patients were examined for the primary form of CVG. Forty-nine
      (44 males and 5 females) out of them were schizophrenic, 16 (14 males and 2
      females) were mentally retarded and the remaining 18 were affected by different
      psychiatric disorders. RESULTS: Three males, 2 mentally retarded and 1
      schizophrenic, were found to be affected and the clinical diagnosis was confirmed
      histologically. CONCLUSION: The high prevalence of primary CVG in males with
      mental retardation might be explained by ethnic factors or by the use of an
      adequate diagnostic methodology, improved by shaving the scalp hair in patients
      suspected to be affected. The term pachydermia verticis gyrata is suggested for
      the primary CVG, which is the most common scalp disorder in such a population.

PMID- 8573925
TI  - Familial multiple cutaneous leiomyomas.
AB  - BACKGROUND: Leiomyomas are rare, benign tumors that originate from the arrector
      muscle of hair follicles (cutaneous leiomyoma, piloleiomyoma), the tunica dartos
      of the scrotum and the mammillary muscle of the nipple (genital leiomyoma), and
      the smooth muscle of blood vessels (angioleiomyoma). OBSERVATIONS: We describe 6
      members of a single family with mostly painful papulonodular cutaneous lesions on
      the limbs, trunk and face. Histological examination of sections stained with
      hematoxylin-eosin and Masson trichromic stain confirmed the diagnosis of
      leiomyoma. All affected women had also uterine myoma. CONCLUSION: Our
      observations support the concept that this entity is an autosomally inherited
      disorder.

PMID- 8573926
TI  - Tolerance to different toilet paper preparations: toxicological and
      allergological aspects.
AB  - BACKGROUND AND DESIGN: A controlled open trial was performed in 40 individuals
      suffering from chronic perianal eczema. Various toilet paper preparations
      representing the conventional type made of pure cellulose, the recycled and the
      moist type were investigated using the patch test as were allergens possibly
      related to toilet paper. In addition, a chronic use test and a repeated rubbing
      test were performed with a conventional and a recycled toilet paper preparation.
      RESULTS: A total of 20 patients could be evaluated in full. A variety of
      reactions were seen in the patch test, most of which were of the allergic type.
      Allergens included many different chemical entities, e.g. preservatives used in
      moist toilet paper such as Kathon CG and Euxyl K 400. In a volunteer allergic to
      Euxyl K 400, allergy to the moist toilet paper regularly used by him was
      established. After discontinuation of its application, perianal dermatitis
      disappeared. In the repeated rubbing test at the forearm, 10 volunteers showed a
      reaction with the recycled paper preparation while no such reaction was seen upon
      the application of the conventional type of toilet paper. The validity of these
      findings was corroborated by corresponding results in the use test. CONCLUSION:
      There is clearly a potential for allergic reactions to components of moist toilet
      paper and reactions to recycled toilet paper presumably irritant by nature. These
      irritant reactions are probably caused by the rough texture of current paper
      types and do not reflect the presence of potentially toxic ingredients such as
      metal salts.

PMID- 8573927
TI  - Retinoids and sebaceous gland activity.
AB  - BACKGROUND AND OBJECTIVE: The marked efficacy of isotretinoin in the treatment of
      acne is undoubtedly due to its potential to inhibit sebaceous gland activity. The
      question arises if the anti-acne effect of new oral retinoids can be predicted by
      using the currently available experimental models. METHODS: We reviewed the
      effects of various oral retinoids on sebum excretion in humans and their efficacy
      in acne. The human data were compared to the results obtained from in vitro and
      animal models. RESULTS: Oral retinoids such as etretinate, acitretin and the so
      called arotinoids were not able to inhibit the sebum production in humans and
      were ineffective against acne. In various animal models (i.e. sebum production in
      rats, flank organ size in hamsters, ear sebaceous gland size in hamster, most of
      these retinoids were shown to be effective. Furthermore, in addition to
      isotretinoin, some retinoids were able to suppress the proliferation of human
      sebocytes in vitro. CONCLUSIONS: The elucidation of the mechanism of action of
      isotretinoin on the sebocyte biology is critical for the search of more reliable
      models and for the discovery of new retinoids with anti-acne activity.

PMID- 8573928
TI  - The antifungal activity of a coal tar gel on Malassezia furfur in vitro.
AB  - OBJECTIVE: Seborrhoeic dermatitis is associated with Malassezia furfur, but the
      exact role of this lipophilic yeast is still unclear. The in vitro antifungal
      activity of a coal tar gel, the base of the gel and coal tar (Stantar) itself has
      been evaluated against 54 different M. furfur strains, isolated from patients
      suffering from dandruff, seborrhoeic dermatitis and pityriasis versicolor.
      METHODS: Minimum inhibitory concentrations (MICs) of the tested agents were
      measured by the agar dilution technique. RESULTS: The coal tar gel was found to
      be able to inhibit growth of 52 out of 54 investigated M. furfur isolates in
      vitro at MIC values between 625 and 10,000 micrograms/ml-corresponding to 3-5
      micrograms/ml coal tar. However, the gel base also appears to be a less potent
      inhibitor of in vitro growth of M. furfur. In addition, it could be demonstrated
      that coal tar alone has an antifungal potential on M. furfur in vitro. MIC values
      from 250 to 5,000 micrograms/ml for coal tar were found. Presumably, both coal
      tar as the active ingredient and the gel base contribute to the in vitro activity
      of the coal tar gel against M. furfur. CONCLUSIONS: It is suggested that the
      effect of coal tar gel ointment in dandruff and seborrhoeic dermatitis therapy in
      vivo may be at least partly due to an antifungal activity of the coal tar but
      also of the gel base.

PMID- 8573929
TI  - Ulcerated haemangioma successfully treated with interferon alfa-2b and topical
      granulocyte-macrophage colony-stimulating factor.
AB  - OBJECTIVE: We tested whether healing and regression could be promoted by
      granulocyte-macrophage colony-stimulating factor and interferon in a 6-month-old
      girl with an ulcerated haemangioma resistant to systemic steroid therapy.
      METHODS: Interferon alfa-2b (Introna, Schering-Plough) was given subcutaneously
      once daily at a dose of 3 million units/m2 for 5.5 months and rhGM-CSF
      (Molgramostim, Leucomax; Sandoz/Schering-Plough) 3.33 units was applied on the
      wound surfaces once and concomitantly with the initiation of interferon therapy.
      RESULTS: The ulcer healed completely within 1 month and the haemangioma almost
      totally regressed within 6 months. CONCLUSION: Local application of rhGM-CSF
      appears to be effective in promoting ulcer healing in an ulcerated haemangioma
      otherwise responding to interferon treatment.

PMID- 8573930
TI  - Multiple bursitis--a case with an unusual skin manifestation.
AB  - Bursitis is a periarticular rheumatism which occurs as a result of trauma,
      infection, metabolic disease or rheumatoid arthritis. The disease is usually
      manifested as a solitary lesion except in a few reported cases of multiple
      lesions. We describe here a case of bursitis in a 58-year-old woman with
      multifocal cystic lesions containing sterile bloody or yellowish fluid in the
      four extremities. Serological abnormalities were also noted, suggesting the
      presence of rheumatoid arthritis or another autoimmune connective tissue disease.

PMID- 8573931
TI  - Multiple squamous-cell carcinomas of the scalp and chronic myeloid leukemia.
AB  - A 67-year-old patient with chronic myeloid leukemia for 4 years rapidly developed
      multiple squamous-cell carcinomas on the scalp. We discuss the role of
      chemotherapy, chronic immunosuppression, chronic sun exposure and of possible
      genetic factors.

PMID- 8573932
TI  - X-linked dominant chondrodysplasia punctata (Happle syndrome) with uncommon
      symmetrical shortening of the tubular bones.
AB  - We describe the case of a 13-year-old girl suffering from chondrodysplasia
      punctata, associated with ichthyosis arranged along Blaschko's lines, follicular
      atrophoderma, cicatricial alopecia and coarse, lusterless hair. The patient also
      showed a congenital cataract of the right eye, dysplastic facial appearance and
      symmetrical shortening of the tubular bones. The pathogenetic concept of
      functional X-chromosome mosaicism is reviewed as well as the recent results
      obtained by molecular research that have failed, so far, to solve the problem of
      regional assignment of the underlying X-linked gene.

PMID- 8573933
TI  - Multiple malignant melanoma and squamous-cell carcinoma in a burn scar.
AB  - Malignant melanoma arising in a burn scar is very rare. Only 12 cases have been
      reported until now. We report a case of multiple malignant melanoma and squamous
      cell carcinoma arising in the same burn scar. Reported cases of malignant
      melanoma arising in burn scars are also reviewed. Results of immunohistochemical
      studies and HLA typing of our patient and a review of previous cases suggest the
      aggressive behavior of malignant melanoma in burn scars.

PMID- 8573934
TI  - Fusarium infection with unusual skin lesions in a patient with acute lymphocytic
      leukemia.
AB  - A 27-year-old woman with acute lymphocytic leukemia developed red painful skin
      lesions, asymmetrically distributed over the face and extremities. They gradually
      increased in size and number, and in the center of each lesion blisters appeared
      followed by central necrosis with surrounding erythema. In several lesions the
      central necrosis was covered with a white powder shown to be fungal mycelium.
      Cultures from skin lesions and blood showed a Fusarium species. The skin lesions
      are helpful in recognizing this deep fungal infection in an immunocompromised
      host.

PMID- 8573935
TI  - A case of angiocentric T-cell lymphoma presenting as lethal midline granuloma.
AB  - A case of angiocentric T-cell lymphoma with glabellar skin being the only
      affected site was reported. A 43-year-old woman had a several months' history of
      glabellar swelling followed by progressive and destructive ulceration of the
      region. Histopathology of the biopsied specimen showed panniculitis with atypical
      lymphocytes and degenerative vessels filled with atypical cells. Most of the
      infiltrated lymphocytes were positive for CD2, CD3, CD4 and CD5. Antibodies to
      Epstein-Barr virus were detected in the patient serum. Intensive chemotherapy
      using a protocol of the L17M regimen was partially effective for clinical
      manifestations. Angiocentric T-cell lymphoma presenting as lethal midline
      granuloma is a rare but distinct entity with an acute fatal course.

PMID- 8573936
TI  - Senile lip licking.

PMID- 8573937
TI  - Gianotti-Crosti syndrome in an adult after influenza virus vaccination.

PMID- 8573938
TI  - Confluent and reticulated papillomatosis: response to topical calcipotriol.

PMID- 8573939
TI  - Nail pigmentation due to roxithromycin.

PMID- 8573940
TI  - Olaquindox-induced persistent light reaction treated by Escherichia coli filtrate
      (Colibiogene)

PMID- 8573941
TI  - Topical photodynamic therapy in verrucae. A pilot study.
AB  - BACKGROUND: Topical photodynamic therapy (PDT) has shown good response rates in
      solar keratoses and superficial skin cancers. OBJECTIVE: To investigate the
      efficiency and tolerance of PDT in refractory verrucae vulgares. METHOD: In an
      open pilot study, 6 patients were treated with 5-aminolevulinic acid-PDT and
      followed up for 2 months. RESULT: One patient showed a complete response, the
      other 5 patients were treatment failures. CONCLUSION: Topical PDT is probably not
      efficient in treating verrucae vulgares.

PMID- 8573942
TI  - A simple quantitative culture of Malassezia spp. in HIV-positive persons.
AB  - BACKGROUND: Etiological role of Malassezia spp. remains controversial in certain
      skin diseases. OBJECTIVE: To adapt a 'tape method' for quantitative culture of
      Malassezia spp. METHOD: Samples for culture were taken from clinically normal
      forehead skin of HIV-positive and negative persons by stripping with a tape that
      was then placed on Leeming & Notman medium. The number of colonies was counted
      after 14 days. RESULTS: 74/78 (94.8%) cultures were positive, for a median count
      of 9 CFU/tape (range 0 to > 200). High skin density of Malassezia spp., defined
      as more than 100 CFU/tape, was found in 7/38 (18.4%) HIV-positive persons and was
      absent (0/40) in the HIV-negative group (p < 0.01). CONCLUSION: The method used
      is simple, unexpensive and reliable. High Malassezia spp. density was only found
      in HIV-positive patients.

PMID- 8573943
TI  - Lichen planus of the eyelids.
AB  - Ocular involvement of lichen planus (Lp) is a rare event. Only 10 cases with Lp
      of the eyelids have been reported in the literature. Ocular Lp may also affect
      mucosal surfaces of the eye and lead to cicatrizing conjunctivitis. Lp of the
      eyelids may appear as isolated lesions and in those cases diagnosis is very
      difficult. Lp should be considered in the differential diagnosis of all
      erythematous and papular eruptions of the eyelids together with lupus
      erythematosus, psoriasis vulgaris or contact dermatitis.

PMID- 8573944
TI  - Intraepidermal IgA pustulosis preceding a CD30+ anaplastic large T-cell lymphoma.
AB  - We report the case of a 62-year-old patient with an extracutaneous CD30+
      anaplastic large T-cell lymphoma which was preceded by intraepidermal IgA
      pustulosis (IEAP). The clinical picture was identical to Sneddon-Wilkinson
      disease and histologic examination showed subcorneal pustules with slight
      acantholysis. Direct immunofluorescence exclusively revealed IgAK deposits on the
      plasma membrane of suprabasal keratinocytes. Indirect immunofluorescence and
      immunoelectrophoresis showed no evidence of monoclonal IgA gammopathy. IEAP
      responded to dapsone treatment (100 mg/day). Two months after disappearance of
      active cutaneous lesions, the patient developed generalized lymphadenopathy due
      to CD30+ anaplastic T-cell lymphoma.

PMID- 8573945
TI  - Hypohidrotic ectodermal dysplasia with recurrent otitis and sebaceous gland
      hypertrophy of the face.
AB  - An isolated affected 19-year-old male with hypohidrotic ectodermal dysplasia
      (HED) had rare features of the syndrome such as recurrent otitis and multiple
      sebaceous gland papules of the face. Sebaceous gland hypertrophy is puzzling in
      the context of HED.

PMID- 8573947
TI  - The impact factor of Dermatology.

PMID- 8573946
TI  - Angiosarcoma of the scalp. A case with a particularly aggressive evolution.
AB  - A 80-year-old woman presented with a spontaneously bleeding wound on her scalp.
      The diagnosis of angiosarcoma was made based on histopathological examination of
      the second biopsy 1 month later. At that time, a large hematoma was present on
      the scalp and forehead with two bleeding erosions and numerous small blue-black
      nodules as well as a right cervical lymphadenopathy. The patient was treated by
      wide-field electron-beam radiotherapy, which showed no effect. The particularly
      aggressive evolution of this angiosarcoma led to death within less than 2 months.

PMID- 8573948
TI  - Amphotericin B infusion-related toxicity: comparison of two- and four-hour
      infusions.
AB  - OBJECTIVE: To investigate the influence of infusion duration on infusion-related
      adverse effects (IRAEs) associated with prophylactic or treatment regimens of
      amphotericin B in patients with leukemia/bone marrow transplant (BMT). DESIGN:
      Randomized, double-blind, 2-arm, complete crossover, prospective clinical trial.
      SETTING: A university-affiliated tertiary care teaching hospital. PARTICIPANTS:
      The study population consisted of 25 consecutive patients with leukemia/BMT who
      received 162 prophylactic regimen infusions and 169 treatment regimen infusions
      of amphotericin B via a central line. Prior to each infusion all patients
      received a parenteral IRAE prophylaxis regimen of diphenhydramine 25 mg and
      hydrocortisone 25 mg. No test doses or incremental amphotericin B doses were
      administered. Patients were monitored closely for IRAEs, which were documented by
      using a standardized data collection form. MAIN OUTCOME MEASURES: The incidence
      and nature of IRAEs during a 6-hour monitoring period following the initiation of
      each infusion was measured. Patients served as their own controls. IRAEs were
      compared according to infusion duration and therapeutic indication. RESULTS:
      Three hundred and thirty-one 2- and 4-hour amphotericin B infusions were
      administered. We found no difference between 2- and 4-hour infusions in the
      incidence and severity of IRAEs, including overall events (29% of 166 2-hour
      infusions vs. 25% of 165 4-hour infusions), chill scores (8% of 166 2-hour
      infusions vs. 7% of 165 4-hour infusions; highest score 7 vs. 6), nausea and
      vomiting (7% vs. 12%; highest score 4 in both groups), fever (3% vs. 2%), highest
      temperature increase (2.4 vs. 1.6 degrees C), systolic hypotension (6% vs. 2%),
      greatest decrease from baseline (40 vs. 62 mm Hg), diastolic hypotension (5% vs.
      3%), and greatest decrease (30 vs. 28 mm Hg) (p > 0.05). Overall, IRAEs were less
      common in prophylactic treatment regimens (35 events [22%] in 162 infusions) than
      in treatment regimens (55 events [32%] in 169 infusions) (p < 0.05). CONCLUSIONS:
      This study demonstrates that patients with leukemia/BMT without myocardial or
      renal dysfunction who receive hydrocortisone and diphenhydramine as
      premedications can tolerate 2-hour central line infusions of prophylactic or
      treatment regimens of amphotericin B as well as 4-hour infusions.

PMID- 8573949
TI  - Evaluation of the pharmacokinetic interaction between cimetidine or famotidine
      and cyclosporine in healthy men.
AB  - OBJECTIVE: To investigate the potential interaction between cimetidine or
      famotidine and cyclosporine in healthy men. DESIGN: All subjects received oral
      cyclosporine at baseline, after the first week of 1 histamine2 (H2)-blocker, and
      a third time after a 1-week washout plus 1 week of the second H2-blocker. Blood
      samples were collected just before each dose of cyclosporine and for up to 36
      hours afterward for pharmacokinetic analysis. SETTING: A college of pharmacy in a
      university teaching hospital. PARTICIPANTS: The study population consisted of 8
      healthy men at least 19 years of age. MAIN OUTCOME MEASURES: Cyclosporine
      concentrations in whole blood were measured using a polyclonal fluorescence
      polarization immunoassay. Cyclosporine pharmacokinetic parameters during each of
      the 3 treatment periods were compared. RESULTS: The average times to maximum
      cyclosporine concentrations were similar between baseline (3.2 h), cimetidine
      (2.9 h), and famotidine (3.6 h) dosing periods. There were no significant
      differences in area under the curve, half-life, or maximum concentration during
      the 3 dosing periods. CONCLUSIONS: Neither cimetidine or famotidine produced a
      significant change in the pharmacokinetics of single-dose oral cyclosporine in
      healthy men.

PMID- 8573950
TI  - Bioelectrical impedance analysis as an assessment of diuresis in congestive heart
      failure.
AB  - OBJECTIVE: To compare changes in bioimpedance parameters and calculated total
      body water (TBW) with conventional measurements used to assess the efficacy of
      diuretic therapy in the treatment of heart failure. SETTING: A Veterans Affairs
      tertiary care, teaching hospital. SUBJECTS: Twelve patients with New York Heart
      Association (NYHA) class III congestive heart failure (CHF). DESIGN: Prospective,
      consecutive sample, cohort, open label. INTERVENTIONS: Parenterally administered
      furosemide; clinically dictated, outcome-oriented, adjunctive therapy of CHF.
      OUTCOMES: Bioelectrical impedance analysis (BIA) parameters, measured volume of
      diuresis and changes in body weight, defined clinical endpoints (NYHA criteria).
      RESULTS: Three days of diuretic therapy with furosemide (oral and/or intravenous)
      for CHF was associated with a measured weight loss of 4.1 +/- 0.6 kg and
      statistically significant increases in resistance and reactance of 20.8% +/- 2.7%
      and 22.7% +/- 6.1%, respectively (p < 0.005). Calculated TBW using BIA parameters
      and standard equations decreased on average by 6.1 +/- 0.6 L or 11.2% +/- 1.1% (p
      < 0.001). A significant inverse correlation was observed between change in
      measured body weight and total body reactance (p = 0.02). CONCLUSIONS: Single
      frequency BIA appears to have limited clinical usefulness as a method of
      assessing diuretic therapy in the management of CHF. Its greatest usefulness
      appears to lie in the assessment of serial changes in individual patients and
      patient populations that are physiologically or metabolically homogeneous.
      Further studies are needed to establish the validity of BIA in patients with
      decompensated CHF.

PMID- 8573951
TI  - Difference between the measured and ordered dose of catecholamine infusions.
AB  - OBJECTIVE: To measure the actual concentrations of dopamine, dobutamine, and
      epinephrine in infusates prepared for patients, and to compare these
      concentrations with those of the dopamine HCl, dobutamine, and epinephrine HCl
      infusates that had been prescribed to evaluate drug preparation accuracy. DESIGN:
      Prospective, unblind study. SETTING: Pediatric intensive care unit in a tertiary
      care teaching hospital. PARTICIPANTS: All dopamine, dobutamine, and epinephrine
      infusions ordered for patients during the 2-month study period were eligible for
      inclusion in the study. MEASUREMENTS: Daily samples of dopamine, dobutamine, and
      epinephrine infusates that were prepared for 41 pediatric patients were obtained;
      the infusate catecholamine concentration was measured by HPLC and compared with
      the ordered concentration. The concentration than was multiplied by the rate of
      infusion to determine the catecholamine dose. MAIN RESULTS: There were
      significant differences between the measured doses of dopamine, dobutamine, and
      epinephrine and the dopamine HCl, dobutamine, and epinephrine HCl doses (p =
      0.0001, p = 0.039, and p = 0.0009, respectively) that had been ordered because of
      preparation inaccuracies. Failure to account for the HCl salt in the stock drug
      accounted for some, but not all, of the inaccuracy of the dopamine HCl and
      epinephrine HCl infusates. There was a wide interday variability in the measured
      catecholamine dosage in patients receiving the same dose for 3 days or more.
      CONCLUSIONS: There are daily fluctuations in the preparation of dopamine,
      dobutamine, and epinephrine infusates that could alter the amount of drug
      actually delivered to critically ill patients and potentially contribute to their
      hemodynamic instability.

PMID- 8573952
TI  - Acute myocardial infarction treatments in 58 Italian hospitals: a drug
      utilization survey.
AB  - OBJECTIVES: To provide an updated and comprehensive profile of therapeutic
      practice in the management of acute myocardial infarction (AMI) in a sample of
      Italian hospitals, and to test the possible role of a network of hospital
      pharmacists in providing drug utilization data. DESIGN: Prospective drug
      utilization survey. Participating pharmacists collected information on patients
      consecutively admitted to the hospital with a suspected AMI. The form reproduced
      those adopted in the Gruppo Italiano per lo Studio della Sopravvivenza
      nell'Infarto miocardico trials. SETTING: Fifty-eight general hospitals in Italy
      belonging to the National Health Service, 6 of which are teaching hospitals.
      Thirty-four hospitals recruited patients from a coronary care unit, 10 from
      intensive monitoring beds in cardiology wards, and 14 from an intensive care
      unit. PARTICIPANTS: The study population consisted of patients consecutively
      admitted with a suspected AMI from May 31 through July 5, 1993. MAIN OUTCOME
      MEASURES: The management of AMI in terms of the use of drugs and nonpharmacologic
      treatments is described. RESULTS: Of the 676 patients recruited for the study,
      47.8% received thrombolytic therapy; alteplase was the preferred agent (55.4% of
      treated patients). The use of thrombolytic therapy varied significantly according
      to different demographic and clinical parameters such as age, sex, delay from the
      onset of symptoms to admission, and Killip scale class. During the first day of
      hospitalization 63.9% of patients received aspirin, 83.3% received nitrates,
      24.8% received beta-blockers, and 77.1% received heparin therapy. CONCLUSIONS:
      Thrombolytic therapy was prescribed in a higher percentage of patients than is
      reported in the US, but lower than that reported in large trials. That a low
      percentage of patients who experienced a long delay between the onset of symptoms
      and admission as well as elderly patients received thrombolytic therapy reflects
      the lower expectations of clinicians for these subgroups of patients. A low
      proportion of patients received aspirin therapy. This study showed that in Italy
      an institutional network of hospital pharmacists could be interested observers of
      therapeutic practice, but further training is needed before high-quality data can
      be collected.

PMID- 8573953
TI  - Compatibility of ondansetron hydrochloride with meperidine hydrochloride for
      combined administration.
AB  - OBJECTIVE: To determine the physical compatibility and chemical stability of
      ondansetron hydrochloride 0.1 and 1 mg/mL with meperidine hydrochloride 4 mg/mL
      admixed in NaCl 0.9% injection USP. DESIGN: Triplicate test solutions of the
      drugs in NaCl 0.9% injection USP were prepared and stored at 4, 22, and 32
      degrees C. Samples were removed initially and at various time points over 31 days
      and were stored at -70 degrees C until they were analyzed. Physical compatibility
      was assessed by measuring solution turbidity with a color-correcting turbidimeter
      and particle content with a light-obscuration particle sizer/counter, as well as
      by visual assessment. Chemical stability of the drugs was determined using a
      stability-indicating HPLC analytic method. Duplicate determinations were
      performed on each sample to measure the concentration of each drug. RESULTS: All
      admixtures were found to exhibit no visual or subvisual changes of consequence in
      turbidity or particle content at all observation points. Further, little or no
      loss of any of the drugs occurred in any concentration throughout the study.
      CONCLUSIONS: The physical compatibility and chemical stability of ondansetron
      hydrochloride with meperidine hydrochloride under the conditions of this study
      have been established for 7 days at 32 degrees C and 31 days at 4 and 22 degrees
      C.

PMID- 8573954
TI  - Polyethylene glycol nephrotoxicity secondary to prolonged high-dose intravenous
      lorazepam.
AB  - OBJECTIVE: To report a patient with a probable acute tubular necrosis (ATN)
      induced by chronic exposure to polyethylene glycol (PEG)-400 via long-term,
      massive dosage of intravenous lorazepam. CASE SUMMARY: A 57-year-old man with a
      history of alcohol abuse was admitted to the intensive care unit for acute
      respiratory failure. Lorazepam therapy was initiated in anticipation of alcohol
      withdrawal. Dosages up to 18 mg/h were required to provide adequate sedation and
      optimize ventilation. On day 43, the patient developed oliguric ATN of unknown
      etiology. The cumulative intravenous lorazepam dose was 4089 mg, equivalent to
      approximately 220 mL of PEG-400. Blood urea nitrogen concentrations followed a
      pattern that paralleled lorazepam dosage increases and decreases. Protein and
      granular casts were evident in urinalyses performed on days 12 and 29. The
      patient eventually experienced complete recovery. DISCUSSION: ATN associated with
      intravenous PEG was last reported in 1959 in 6 of 32 patients receiving a
      cumulative PEG-300 dose of 120-200 mL over 3-5 days via an intravenous
      nitrofurantoin preparation. Two of the 6 patients died. Chronic administration of
      intravenous PEG to rabbits over a 5-week period has caused cloudy swelling of the
      renal tubular epithelium, increased blood urea concentrations, and death in some
      animals. CONCLUSIONS: ATN probably resulted from chronic PEG exposure via massive
      doses of lorazepam injection, possibly enhanced by concurrent administration of
      vancomycin.

PMID- 8573955
TI  - Vigabatrin-associated reversible acute psychosis in a child.
AB  - OBJECTIVE: To describe a child with vigabatrin-associated reversible acute
      psychosis and review the literature reports on this adverse effect. CASE SUMMARY:
      A 7-year-old boy with intractable epilepsy developed acute psychosis 3 days after
      initiating a rapid vigabatrin dosage escalation. All symptoms resolved within 48
      hours after vigabatrin therapy was withdrawn. Two months later, reinitiation of
      vigabatrin therapy using a slower dosage escalation was well-tolerated by the
      patient, and he currently is being treated with vigabatrin successfully.
      DISCUSSION: Although vigabatrin-associated psychosis is rare, a few cases have
      been reported in predisposed adult patients, especially in the early stages of
      treatment. The mechanism of this reaction remains unclear and its incidence is
      unknown. To our knowledge, there has been no previous report of this adverse
      effect in children. CONCLUSIONS: Caution must be taken in children with
      predisposing factors at the beginning of vigabatrin therapy.

PMID- 8573957
TI  - Pseudomonas aeruginosa as a cause of infectious diarrhea successfully treated
      with oral ciprofloxacin.
AB  - OBJECTIVE: To describe an immunocompromised patient (without AIDS) with
      nosocomial infectious diarrhea caused by Pseudomonas aeruginosa. Oral
      ciprofloxacin therapy proved to be effective. CASE SUMMARY: An 80-year-old woman
      with type II diabetes mellitus and hypertension developed progressive renal
      insufficiency, was hospitalized because of uremia, and underwent hemodialysis.
      When the patient developed hematochezia, Duke's C sigmoid colon cancer was
      detected and successfully resected. She received broad-spectrum antibiotics in
      the perioperative period. The patient then developed profuse diarrhea associated
      with abdominal cramping, a low-grade fever, prostration, and headache. The
      patient then started to received vancomycin 500 mg po qid empirically. Four days
      later, the diarrhea continued unabated, the Clostridium difficile titer was
      negative, and the vancomycin therapy was stopped. However, the stool culture was
      positive for heavy growth of P. aeruginosa sensitive to ciprofloxacin. The
      patient then began to receive ciprofloxacin 500 mg po bid. Within 3 days the
      diarrhea stopped. Oral ciprofloxacin therapy was continued for 10 days and the
      patient remained free of symptoms with formed stools thereafter. DISCUSSION:
      Diarrhea following the use of broad-spectrum antibiotics implicates
      pseudomembranous colitis as the cause. The patient did not respond to oral
      vancomycin therapy and had a negative stool assay for C. difficile toxin. This
      patient was believed to have Pseudomonas enteritis, which was confirmed by 2
      positive stool cultures. The administration of oral ciprofloxacin therapy stopped
      her diarrhea with a rapid resolution of symptoms. CONCLUSIONS: P. aeruginosa as a
      cause of infectious diarrhea is unusual. When it occurs, it usually represents a
      nosocomial infection in an immunocompromised host. This report illustrates that
      oral ciprofloxacin therapy is effective for Pseudomonas enteritis, with rapid
      resolution of symptoms.

PMID- 8573956
TI  - Opioid-induced muscle activity: implications for managing chronic pain.
AB  - OBJECTIVE: To increase awareness of opioid-induced involuntary muscle
      hyperactivity and to present management options. CASE SUMMARY: A ventilator
      dependent 71-year-old man presented with pain caused by metastatic lung cancer.
      Transdermal fentanyl therapy was titrated to 200 micrograms/h. Two days later a
      continuous morphine infusion was initiated because of frequent administration of
      oral morphine solution for breakthrough pain. The patient became progressively
      less responsive and began exhibiting involuntary muscle hyperactivity thought to
      represent breakthrough pain. Despite the inability to assess pain control
      effectively in this unresponsive patient, the morphine infusion rate was
      increased from 22 to 717 mg/h within 7 days. No change in muscle hyperactivity
      was observed. DISCUSSION: Over the last decade involuntary muscle hyperactivity
      has been documented as an adverse effect of chronic opioid therapy. The
      literature describing the incidence of this toxicity, possible risk factors for
      its development, and recommendations for its management are discussed.
      CONCLUSIONS: The occurrence of muscle hyperactivity in an unresponsive patient
      receiving chronic opioid therapy may represent opioid toxicity. Recommendations
      for managing opioid-induced muscle hyperactivity include reduction of the opioid
      dosage and/or administration of clonazepam therapy.

PMID- 8573958
TI  - Indapamide-induced severe hyponatremia and hypokalemia.
AB  - OBJECTIVE: To describe 2 patients with severe indapamide-induced hyponatremia and
      hypokalemia and to discuss the incidence and mechanisms of diuretic-induced
      hyponatremia and hypokalemia. CASE SUMMARY: Two women aged 60 and 62 years
      presented with severe hyponatremia (plasma sodium concentrations of 103-104
      mmol/L) and hypokalemia (plasma potassium concentrations of 1.6-2.2 mmol/L) 5-6
      weeks after they received indapamide 2.5 mg/d therapy for arterial hypertension.
      Central nervous system symptoms of hyponatremia were observed in both patients.
      One patient experienced severe postural hypotension, a plasma potassium
      concentration of 1.6 mmol/L, and electrocardiographic abnormalities consistent
      with hypokalemia. Hyponatremia was initially mistaken in this patient for the
      syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Both
      patients recovered completely after withdrawal of indapamide therapy and
      correction of the hyponatremia and hypokalemia. DISCUSSION: Previous studies of
      administration of indapamide 2.5 mg/d for 10-24 months in hypertensive patients
      showed a low incidence (0.6-1.2%) of hypokalemia severe enough to require
      withdrawal of drug therapy. Serum sodium concentrations were unaltered in these
      studies. All case reports, except 1, of indapamide-induced electrolyte
      disturbances described only hypokalemia. CONCLUSIONS: Indapamide can cause both
      severe hypokalemia and hyponatremia. The predominant clinical features can be a
      result of severe hyponatremia. The latter can have diverse clinical presentations
      and may be mistaken for SIADH. As with other diuretics, plasma sodium and
      potassium concentrations must be monitored during indapamide therapy, especially
      in patients at risk for hyponatremia and hypokalemia.

PMID- 8573959
TI  - Effect of vitamin C on plasma lipids.
AB  - OBJECTIVE: To review the effects of vitamin C (ascorbic acid) on plasma lipid
      concentrations, and to address the proposed mechanisms through which vitamin C
      may potentially alter lipid concentrations. DATA SOURCE: A MEDLINE search was
      performed to identify pertinent English-language literature including studies,
      abstracts, and review articles. Key search terms were vitamin C, ascorbic acid,
      lipoproteins, lipids, and atherosclerosis. STUDY SELECTION AND DATA EXTRACTION:
      Studies examining the relationships between vitamin C and plasma lipid
      concentrations including animal, observational, and clinical trials were
      selected. Because there were no large randomized, controlled clinical trials,
      data were extracted from all clinical trials, regardless of design. Review
      articles discussing the effects of vitamin C on plasma lipid concentrations and
      the atherosclerotic process also were included. Pertinent information, as judged
      by the authors, was extracted for discussion. DATA SYNTHESIS: Evidence suggests
      an inverse relationship between vitamin C intake and the development of
      atherosclerosis, although the effect has not yet been proven in clinical trials.
      It has been postulated that this effect might be mediated not only through the
      antioxidant properties of vitamin C, but also through a plasma lipid-modifying
      effect. Data from animal and observational trials suggest that high vitamin C
      concentrations may correlate negatively with concentrations of total cholesterol,
      triglycerides, and low-density lipoproteins and positively with high-density
      lipoproteins. Other studies, however, have not confirmed these findings.
      Similarly, results from clinical trials have been widely variable and
      inconclusive. CONCLUSIONS: Analysis of the literature suggests an association
      between vitamin C and plasma lipid concentrations and a potential role in slowing
      the development of atherosclerosis. Significant variations and inadequacies in
      trial design, however, prohibit definitive conclusions. On the basis of these
      preliminary data, it appears that there is justification for additional well
      designed trials to further evaluate the relationship between vitamin C and plasma
      lipid concentrations.

PMID- 8573960
TI  - Cigarette smoking and clinically significant drug interactions.
AB  - OBJECTIVE: To review clinically significant drug interactions associated with
      cigarette smoking. DATA SOURCES: Data from scientific literature were identified
      by using a MEDLINE search. Data were extracted, evaluated, and summarized for
      this review. STUDY SELECTION: Findings and experiences were selected from
      clinical, epidemiologic, and pharmacokinetic studies; review articles; case
      studies; abstracts; letters to the editor, and proceedings. DATA EXTRACTION: Data
      from human studies published in English were evaluated. Only interactions deemed
      clinically significant are included in this review. Conclusions derived from
      review articles on the subject of smoking and drug interactions also were used.
      DATA SYNTHESIS: Cigarette smoking can affect drug therapy via pharmacokinetic and
      pharmacodynamic mechanisms. Pharmacokinetic drug interactions are presented for
      theophylline, tacrine, insulin, flecainide, propoxyphene, propranolol, diazepam,
      and chlordiazepoxide. Pharmacodynamic interactions are described for
      antihypertensive and antianginal agents, antilipidemics, oral contraceptives, and
      histamine2-receptor antagonists. CONCLUSIONS: Cigarette smoking can reduce the
      efficacy of certain drugs or make drug therapy more unpredictable.
      Pharmacokinetic interactions may cause smokers to require a larger dosage of
      certain drugs through an increase in plasma clearance, a decrease in absorption,
      an induction of cytochrome P450 enzymes, or a combination of these factors.
      Pharmacodynamic interactions may increase the risk of adverse events in smokers
      with cardiovascular or peptic ulcer disease, and in women who smoke and use oral
      contraceptives. Healthcare professionals should pay special attention to patients
      with these profiles and should try to prevent cigarette smoking or encourage
      patients to discontinue this addictive habit.

PMID- 8573961
TI  - Rifabutin-associated uveitis.
AB  - OBJECTIVE: To review rifabutin-associated uveitis and discuss the mechanism and
      potential role of drug interactions with clarithromycin and fluconazole in
      contributing to this adverse event. DATA SOURCES: A MEDLINE search (1991 through
      September 1994) of English-language literature using the main MeSH headings
      "rifabutin" and "uveitis" and the subheadings "adverse effects" and "chemically
      induced." Relevant articles also were selected from references of identified
      articles. Abstracts from recent medical conferences of infectious diseases,
      pharmacology, and HIV were screened for additional data. STUDY SELECTION AND DATA
      EXTRACTION: All articles and abstracts reporting uveitis potentially related to
      rifabutin were considered for inclusion. Fifty-four cases were identified.
      Pertinent information from the case reports, as judged by the authors, was
      selected and synthesized for discussion. DATA SYNTHESIS: Rifabutin is being
      prescribed increasingly for the treatment and prophylaxis of Mycobacterium avium
      complex (MAC) infection in the HIV-infected population. Uveitis was initially
      thought to be a rare, dose-limited complication of rifabutin therapy. In an early
      dose-ranging tolerance study, uveitis was associated with daily doses of 1200 mg
      or more. Because this toxicity appeared to be dose-related, lower dosages (300
      600 mg/d) of rifabutin were selected for study in subsequent clinical trials.
      More recent reports noting the association of uveitis with these lower dosages of
      rifabutin have raised concerns about the prevalence of this adverse event. In the
      54 identified cases, patients presented with symptoms of unilateral or bilateral
      uveitis from 2 weeks to more than 7 months following initiation of rifabutin
      therapy. In all reported cases, patients were receiving concurrent therapy with
      clarithromycin and/or fluconazole, both of which have inhibitory effects on
      rifabutin metabolism. In most cases, uveitis resolved within 1-2 months following
      discontinuation of rifabutin with or without administration of topical
      corticosteroids. CONCLUSIONS: Rifabutin is prescribed frequently for the
      prophylaxis and treatment of MAC infection, especially in patients with HIV.
      Uveitis is a rare, dose-related toxicity of this therapy. The risk of rifabutin
      associated uveitis may be increased in patients receiving concurrent therapy with
      clarithromycin or fluconazole because of drug interactions. Patients receiving
      therapy with combinations of any of these agents should be warned about signs and
      symptoms of uveitis and be monitored closely for the development of rifabutin
      toxicity. If uveitis develops, rifabutin therapy should be discontinued promptly.

PMID- 8573962
TI  - Rho Chi Lecture Award. Is something broken that requires fixing?

PMID- 8573964
TI  - Cisapride for the treatment of chronic idiopathic constipation.
AB  - Cisapride appears to be useful as therapy for chronic constipation that is not
      associated with underlying organic abnormalities or pregnancy and that is
      refractory to other treatments, such as increased dietary fiber intake or bulk
      laxatives. Dosages of cisapride that have demonstrated efficacy in chronic
      constipation range from 5 mg po tid to 20 mg po bid. Treatment for 8-12 weeks may
      be necessary for an optimal effect to occur. Further studies are needed to
      evaluate the most effective dosage regimen for the treatment of constipation and
      to compare the efficacy and cost-efficiency of cisapride with those of
      conventional therapy. Until these studies are completed, cisapride should not be
      recommended routinely for patients with constipation. However, it may be a viable
      option for patients with chronic idiopathic constipation that is refractory to
      conventional therapy.

PMID- 8573963
TI  - Potential use of gabapentin and lamotrigine.
AB  - Based on the proposed neurotoxic etiology of ALS and possible actions of
      gabapentin and lamotrigine, there is some reason to hope for a beneficial
      response when using these agents in patients with ALS. However, because of the
      lack of evidence supporting this use, the cost of treatment, and the risk of
      adverse effects, there is no rationale for this use before larger, controlled
      clinical trials are completed.

PMID- 8573965
TI  - Potential treatment of amyotrophic lateral sclerosis with gabapentin: a
      hypothesis.
AB  - OBJECTIVE: To provide the biochemical rationale for the use of the new
      anticonvulsant agent gabapentin as a treatment for amyotrophic lateral sclerosis
      (ALS). BACKGROUND: ALS is a neuropathologic disorder of the central nervous
      system characterized by a progressive loss of upper and lower motor neurons.
      Although the etiopathology of ALS is incompletely known, it is hypothesized that
      glutamatergic neurotransmission is related to neuropathology. Glutamate is an
      excitatory amino acid neurotransmitter that is cytotoxic when overexpressed at
      synaptic terminals, probably through a calcium-related mechanism. The
      concentration of glutamate in cerebrospinal fluid is increased in patients with
      ALS. The increased extracellular concentrations of glutamate may be caused by a
      decreased capacity of glutamate transport in brain tissue and/or abnormal
      glutamate metabolism. Recent success with the glutamate release inhibitor
      riluzole in well-controlled clinical trials supports the excitotoxic mechanism of
      neuropathology in patients with ALS. POTENTIAL TREATMENT FOR ALS: Gabapentin has
      demonstrated neuroprotective properties in a model of chronic glutamate toxicity
      in vitro. Although the neuroprotective mechanism of action of gabapentin is
      currently unknown, it is hypothesized here that gabapentin decreases the rate of
      formation of glutamate derived from the branched-chain amino acids (BCAAs)
      leucine, isoleucine, and valine. The proposed decrease in formation of glutamate
      from BCAAs may decrease the pool of releasable glutamate and therefore compensate
      for diminished glutamate uptake capacity and/or abnormal glutamate metabolism in
      patients with ALS. CONCLUSIONS: Based on this rationale, it is proposed that
      gabapentin may provide a beneficial effect in the treatment of patients with ALS.

PMID- 8573966
TI  - Leukocytoclastic vasculitis and hemoptysis after treatment with aceclofenac.

PMID- 8573967
TI  - Compatibility of haloperidol and diphenhydramine in a hypodermic syringe.

PMID- 8573968
TI  - Pharmacoepidemiology graduate course.

PMID- 8573969
TI  - Comment: steroid treatment of mild chronic asthma.

PMID- 8573970
TI  - Comment: lamotrigine dosing.

PMID- 8573971
TI  - Coronary artery surgery.

PMID- 8573972
TI  - Imaging and echocardiography.

PMID- 8573973
TI  - Recent reports on long-term results of coronary artery bypass grafting.
AB  - The treatment of coronary artery disease in general and the results achieved with
      coronary artery bypass grafting in particular continue to be intensely studied.
      Long-term follow-up from ongoing studies and the studies of the role of
      percutaneous interventions continue to provide new information. The refinement of
      our understanding of long-term outcome in various subsets of patients,
      preoperative risk factors, technical modifications, and postoperative
      interventions will influence the selection of appropriate treatment for patients
      with coronary artery disease.

PMID- 8573974
TI  - Developments in surgical techniques for coronary revascularization.
AB  - The wider application of arterial conduits represents a current trend in
      myocardial revascularization. More complex and demanding surgical techniques are
      being developed as alternatives to traditional grafting procedures, in order to
      permit total arterial revascularization in patients with diffuse coronary artery
      disease. The rationale behind this strategy is the expected higher long-term
      patency rate of arterial conduits as compared with vein grafts. Avoidance of
      proximal anastomoses is another argument in favor of coronary revascularization
      with arterial grafts, particularly in patients with atherosclerotic changes in
      the ascending aorta. Although the reported operative results are good, total
      arterial revascularization in multivessel disease is a complex procedure, and
      serious perioperative complications are possible. In planning the
      revascularization strategy, therefore, the surgeon should take into account age,
      clinical condition, coexisting medical problems, coronary anatomy, and left
      ventricular function. The method of myocardial revascularization is an important
      aspect of the surgical procedure and plays a major role in the outcome of the
      operation in the presence of severe left ventricular dysfunction or when the
      operation requires prolonged ischemic times. To avoid the inevitable damaging
      effects of cardiopulmonary bypass and aortic cross-clamping, myocardial
      revascularization is carried out without extracorporeal circulation. This
      technique should be part of the armamentarium of the cardiac surgeon and should
      occasionally be considered in patients who have serious coexisting medical
      problems or severe left ventricular dysfunction.

PMID- 8573975
TI  - Vein graft failure.
AB  - Saphenous vein graft failure is one of the primary reasons for coronary artery
      bypass reoperation. The economic impact alone in this country is staggering in an
      era of intensive cost cutting. The fact that some vein grafts remain free of
      disease for years while the sibling vein develops extensive atherosclerosis
      remains an enigma. Saphenous vein valves have recently attracted interest.
      Repeated angiograms show that vein graft disease invariably is accentuated around
      valves. Studies show that the segment of saphenous vein distal to the valves have
      more accelerated and intense atherosclerosis. Early results of saphenous vein
      bypass grafting may be predicted with some degree of certainty by saphenous vein
      graft biopsy. Attention is now being turned to the hypercoagulable state as a
      cause of graft failure, as this has not been previously addressed. Research into
      pharmacologic agents for maintaining open grafts has had disappointing results
      and aspirin alone is still the single drug of choice to promote patency.
      Preparation of the graft continues to be important because there is direct
      evidence that surgical injury during preparation leads to neointimal thickening
      and vascular smooth muscle proliferation. Although there are some exciting new
      modalities for preventing graft disease, the difficulty in transposing animal
      data to humans and the uncertainty of the biologic similarities of in vitro and
      in vivo endothelial cell biochemistry makes any immediate solution unlikely.
      Therefore an even greater increase in the use of arterial grafts in the near
      future seems likely, even with their associated problems.

PMID- 8573977
TI  - New strategies for intraoperative myocardial protection.
AB  - In the past, most strategies for intraoperative myocardial protection were
      developed in models using nondiseased adult hearts from various animal species.
      In the clinical setting, however, myocardial status in cardiac patients may be
      quite different and there is a need to adapt our current protective strategies to
      the actual pathophysiological status of the heart. In the immature heart as well
      as in the senescent heart, current protective techniques have been shown to be
      deficient and further research is required. New insights have been gained into
      the pathophysiological processes underlying chronic ischemic left ventricular
      dysfunction in the "hibernating" myocardium. It has been shown that viability in
      these hearts is associated with subcellular alterations related to
      dedifferentiation of the myocytes. This finding explains the delayed recovery in
      function of these hearts after revascularization and the need for intraoperative
      protective strategies focusing on the prevention of stunning in the
      nonhibernating segments. Tepid continuous retrograde blood cardioplegia is
      suggested as the optimal technique. Unraveling the mechanisms of preconditioning
      in the heart and understanding endogenous myocardial protection may provide clues
      for novel cardioprotective techniques. Adenosine itself may be used as an adjunct
      to cardioplegia, and treatment with adenosine regulating agents or nucleoside
      transport inhibitors shows promising results. Like adenosine, other
      hyperpolarizing agents (potassium-channel openers) are suggested for arrest of
      the heart instead of the depolarizing agents commonly used in cardioplegia.
      Finally, the role of Na(+)-H+ exchange in the development of ischemic and
      postischemic injury has become more clear. By the use of a new selective Na(+)-H+
      exchange inhibitor, postischemic contracture can be dramatically reduced and
      contractility improved. This opens prospective approaches in emergency coronary
      bypass surgery for evolving myocardial infarction.

PMID- 8573976
TI  - Molecular biology of graft occlusion.
AB  - Whatever the method, the biologic price of restitution of arterial flow through
      or around an obstructed artery is injury to the arterial wall. The artery mounts
      a healing response that in 30% to 60% of procedures exceeds the need. The result
      is formation of a lumen-narrowing lesion composed of smooth muscle cells and
      extracellular matrix with varying amounts of atherosclerotic components. The
      primary player appears to be the smooth muscle cell. For four decades the
      standard model for studying these events has been catheter denudation of arterial
      endothelium in small animals. Molecular biology has provided an enormous amount
      of new information including growth factors, adhesion molecules, receptor binding
      sites, and molecules that up- or down-regulate or maintain a steady state of
      expression of numberless genes in the arterial wall. Predictably, means of
      inhibiting these molecular events have been found. That their clinical trials
      have been universally disappointing should not be surprising given that the
      animal in which the discoveries were made--the rat--is not normally susceptible
      to atherosclerosis and the histology of the rat artery only approximates that of
      the human. Nevertheless, reason for optimism exists because of our increasing
      understanding of the injury response. Recent developments include the use of
      blocking antisense oligonucleotides, blocking antibodies, gene transfer trials,
      and early investigations into the role of the immune system.

PMID- 8573978
TI  - Blood use in cardiac surgery and the limitations of hemodilution.
AB  - The use of blood and blood products in cardiac surgery has undergone marked
      changes over the past three decades. This revolution occurred primarily through
      the study and understanding of hemodilution. This review marks the changes in the
      practice of blood transfusion in cardiac surgery. We review the methods of blood
      conservation through preoperative screening and preparation, intraoperative drug
      therapy and modification of surgical techniques, and postoperative use of shed
      mediastinal blood. We also examine the physiologic effects and limitations of
      hemodilution in adult and pediatric cardiac surgery. Finally, we review the
      recent trends in the use of blood component therapy and the future of blood
      substitutes.

PMID- 8573979
TI  - Aprotinin in patients having coronary artery bypass graft surgery.
AB  - Any therapy must have a benefit and a risk. The benefit of aprotinin therapy in
      reducing bleeding is well known. Data presented over the past 12 months have
      confirmed this efficacy and the superiority and consistency of aprotinin therapy
      in direct comparison with other pharmacologic (desmopressin, tranexamic acid) and
      physical (administration of fresh platelet concentrate) interventions. The debate
      has now changed to focus on issues of the safety of this agent. In particular,
      concerns have been expressed as to the effect of this agent on renal function,
      thrombotic potential (and thus graft patency), and adverse reactions on a second
      exposure. Most recent reports show plasma creatinine concentrations are higher in
      treated than in nontreated patients on the 3rd or 4th postoperative day. The
      concentrations reached were not outside the clinical range, and there were no
      clinical sequelae of this biochemical abnormality. Focused studies have shown no
      effect of the use of aprotinin therapy on early graft patency or the incidence of
      thromboembolic complications. The reporting of hypersensitivity reactions
      following aprotinin administration suggests that the incidence is not different
      to other agents used in open heart surgery. Three reports of fatal or near-fatal
      cardiovascular collapse associated with the use of aprotinin followed the
      apparently inappropriate administration of the agent.

PMID- 8573980
TI  - The inflammatory response to cardiopulmonary bypass and its impact on
      postoperative myocardial function.
AB  - Cardiopulmonary bypass triggers a generalized inflammatory response that is
      largely mediated by activation of polymorphonuclear neutrophils, their adhesion
      to endothelial cells, and the subsequent release of cytotoxic products. It has
      been known for several years that the inflammatory response to extracorporeal
      circulation underlies the occasional development of postoperative organ--in
      particular, lung--dysfunction. It is now increasingly recognized that this
      response can adversely affect myocardial function as well. These harmful effects
      are exerted by a wide spectrum of compounds, regardless of whether they act as
      triggers (complement-derived anaphylatoxins), mediators (cytokines, adhesion
      molecules), or effectors (proteolytic enzymes, oxygen free radicals,
      leukotrienes) of the inflammatory cascade. These considerations suggest that
      future strategies of myocardial protection must not be limited to interventions
      targeted at the heart itself but should also encompass those designed to blunt
      the inflammatory response to cardiopulmonary bypass.

PMID- 8573981
TI  - Role of leukotrienes in coronary artery surgery.
AB  - In recent years there has been a heightened awareness of the importance of
      inflammatory processes in both coronary artery disease and cardiopulmonary
      bypass. Leukotrienes are a group of proinflammatory metabolites of arachidonic
      acid whose biologic effects have led to the postulation that they have a role in
      a broad number of functions and inflammatory disease processes. There is evidence
      to suggest a putative role of leukotrienes in coronary artery disease. In
      particular, the cysteinyl leukotrienes are potent vasoconstrictors of coronary
      arteries and can be generated by cell types known to be found in atherosclerotic
      arteries and that can participate in the process of atherosclerosis. In addition,
      leukotrienes are elevated in patients with cardiac ischemia, and following
      coronary artery bypass graft surgery, suggesting that the leukotrienes as well as
      other inflammatory mediators participate in the pathogenesis of cardiac ischemic
      syndromes. Understanding of the role of mediators involved in coronary heart
      disease and cardiopulmonary bypass could be of great value in managing these
      patients as well as developing new strategies for treatment.

PMID- 8573982
TI  - Recent progress in digital image formatting and current trends in computers:
      their role in digital image storage and telemedicine. Commentary.

PMID- 8573983
TI  - Recent advances in stress echocardiography.
AB  - Stress echocardiography has found acceptance as a routine technique for the
      diagnosis and evaluation of coronary artery disease. This review concentrates on
      recent advances in this technique. New approaches including contrast
      echocardiography, transesophageal stress echocardiography, and color-enhanced
      wall motion analysis may augment its feasibility and can be used to assist in the
      interpretation of these studies. The combination of dobutamine with atropine is
      safe, effective, and superior to the alternatives in patients who cannot
      exercise. However, in active patients, exercise appears to provide the optimal
      stress. Finally, recent studies have documented promising results regarding the
      efficacy of stress echocardiographic techniques for prognostic evaluation and the
      diagnosis of viable myocardium.

PMID- 8573984
TI  - Novel techniques of coronary artery imaging.
AB  - Intravascular ultrasound imaging and intracoronary Doppler flow mapping are two
      new techniques used to diagnose coronary artery disease. One provides detailed
      information about coronary morphology; the other assesses coronary function. By
      combining these two techniques, mechanisms of coronary syndromes that were
      previously unclear can be elucidated. The preliminary use of electron beam
      computed tomography in scanning of the coronary arteries has demonstrated the
      potential to identify severe coronary artery disease noninvasively. Coronary
      arteries can be imaged by intravenous injection of contrast material. Magnetic
      resonance imaging and positron-emission tomography are also used for the
      noninvasive visualization coronary arteries. Both techniques have been tested
      after interventions, which offers the potential to study myocardial function and
      perfusion.

PMID- 8573985
TI  - Recent progress in quantitative echocardiography.
AB  - Substantial progress has been made recently in quantitating a variety of
      functional or morphologic parameters with echocardiography. Doppler techniques
      for measuring regurgitant flow rate and regurgitant orifice area in mitral and
      tricuspid regurgitation have become well established, along with other Doppler
      measures of regurgitation severity, such as proximal jet width. Doppler
      measurement of diastolic flow propagation in the left ventricle is emerging as a
      promising, albeit fascinatingly complex way of looking at diastolic function.
      Doppler velocimetry has been extended to wall motion, yielding color maps of
      tissue, an entirely new tool for assessing myocardial function and its timing. In
      the field of two-dimensional data processing, automatic on-line boundary
      detection based on integrated ultrasound backscatter has been used for volume and
      cardiac output calculations. Finally, three-dimensional reconstruction of cross
      sectional images now has been well validated for in vivo measurements of heart
      cavity volumes and masses.

PMID- 8573986
TI  - Magnetic resonance imaging of the heart and its role in current cardiology.
AB  - Magnetic resonance imaging has been demonstrated to be useful in the assessment
      of aortic and pericardial disease, cardiac masses, and congenital heart disease.
      Recently, developments in rapid imaging, assessment of regional function,
      evaluation of intracardiac shunts and valvular regurgitation, and magnetic
      resonance coronary angiography have been achieved, indicating an increasing role
      for magnetic resonance techniques in clinical cardiology.

PMID- 8573987
TI  - New agents and new techniques in nuclear cardiology.
AB  - With the availability of new 99mTc perfusion tracers, nuclear cardiology imaging
      techniques can provide information on myocardial blood flow and left ventricular
      function from a single imaging session. Ejection fraction, regional wall motion,
      and changes in wall thickness can be measured and specificity can be improved by
      gating the images, without increasing the acquisition time. Similarly, the
      ability to use conventional gamma cameras to image important positron-emission
      tomography radiotracers, such as fluorodeoxyglucose, allow cost-effective and
      widespread applications of positron-emission tomography technology. Thus, new
      radiotracers and imaging techniques in nuclear cardiology provide incremental and
      cost-effective diagnostic information in the assessment of coronary artery
      disease.

PMID- 8573988
TI  - Potential role of thiazolidinediones in older diabetic patients.

PMID- 8573989
TI  - Pharmacological intervention in older patients with rheumatoid arthritis. Quality
      of life aspects.
AB  - Despite the rather pessimistic outlook regarding the long term effects of
      pharmacological treatment of patients with rheumatoid arthritis (RA), there is no
      doubt that drug interventions can affect quality of life (QOL). The disease has a
      significant impact upon physical, psychological and social function, and QOL
      optimisation should cover all these dimensions. Swelling of joints and pain are
      important manifestations in assessing RA since these may result in sleep
      disturbances as well as depressed mood. This might be particularly significant
      for older persons with RA. Outcome parameters of RA can be divided into short,
      intermediate and long term. The long term results are quite disappointing with
      regard to disability and premature death. However, more intermediate outcome
      measures related to QOL might improve after pharmacological interventions.
      Patient preferences and expectations with regard to the outcome of
      pharmacological interventions are important parameters to assess. When assessing
      older patients with RA with QOL instruments, it is recommended that
      questionnaires are fairly short and easy to complete. Adverse effects of
      pharmacological interventions are important factors to monitor in QOL assessment
      in older patients with reduced remaining life span.

PMID- 8573990
TI  - Diagnosis and treatment of dyspepsia in the elderly.
AB  - Although dyspeptic symptoms are very common, the vast majority of patients have
      modest symptoms and rarely seek medical advice. The major organic causes of
      dyspepsia are chronic peptic ulcer disease, gastro-oesophageal reflux disease and
      malignancy. Functional dyspepsia is very common. In the fit elderly patient,
      prompt investigation may be more appropriate than empirical treatment in view of
      the higher proportion of patients with organic disease and the likelihood of
      malignancy. The symptoms of peptic ulceration and gastro-oesophageal reflux
      disease are often atypical in the elderly population. Frail patients, especially
      those with multiple pathology, should be treated empirically in the first
      instance. Empirical treatment should be with histamine H2-receptor antagonists or
      prokinetic agents. Drug treatment is not always required in dyspepsia and should
      be avoided where possible, especially given the increased risk of drug
      interactions and poor compliance in the elderly. For those patients with
      documented non-malignant organic disease, the advent of the H2-receptor
      antagonists, proton pump inhibitors, prokinetic drugs and regimens which
      eradicate Helicobacter pylori means that treatment is almost always successful.

PMID- 8573992
TI  - Diclofenac/misoprostol. A review of its pharmacology and therapeutic efficacy in
      painful inflammatory conditions.
AB  - Diclofenac is a well established nonsteroidal anti-inflammatory drug (NSAID) used
      in the treatment of a variety of painful inflammatory conditions. Although
      generally well tolerated, diclofenac, like other NSAIDs, is associated with
      gastrointestinal adverse effects which infrequently can be serious and/or life
      threatening. Misoprostol, a prostaglandin E1 analogue, reduces the incidence of
      NSAID related ulcers, both gastric and duodenal. The lack of conclusive
      pharmacoeconomic data for misoprostol and the widespread use of NSAIDs makes
      routine administration of misoprostol difficult to justify for all NSAID users.
      However, it appears to be an economically warranted approach in the elderly, who
      are at particularly high risk for NSAID-related gastrointestinal complications.
      The fixed combination of diclofenac 50mg and misoprostol 200 micrograms
      administered 2 to 3 times daily for 4 to 12 weeks has shown equivalent
      therapeutic efficacy to diclofenac (alone or combined with placebo), piroxicam
      and naproxen, and was slightly more effective than ibuprofen in clinical studies
      in patients with a variety of painful inflammatory conditions. No significant
      differences in therapeutic efficacy were noted between elderly (aged > or = 65
      years) and younger patients in these studies. Gastrointestinal adverse events are
      common with diclofenac and misoprostol, administered alone or in combination.
      Diarrhoea (presumably attributable to the misoprostol component) appears to be
      more frequent in diclofenac/misoprostol recipients than in those receiving
      diclofenac alone or combined with placebo. However, diclofenac/misoprostol
      recipients had significantly fewer gastroduodenal ulcers at the end of treatment
      relative to patients receiving comparators in clinical trials. In addition, the
      types and incidences of adverse events are similar in elderly and younger
      patients. Routine ulcer prophylaxis with misoprostol in all NSAID users is not
      warranted from a pharmacoeconomic viewpoint. In common with other fixed
      combination products, dosage flexibility is somewhat compromised with
      diclofenac/misoprostol. However, once drug dosages are determined in the
      individual patient, the fixed combination of diclofenac and misoprostol offers
      the potential for increased patient convenience and possibly patient compliance,
      and lower drug acquisition costs than those of the individual drugs used
      together. Thus, it should be considered a useful treatment option in
      appropriately selected patients with a high risk for serious NSAID-related
      gastrointestinal complications who require NSAID therapy.

PMID- 8573994
TI  - Molecular role of sulfated glycoprotein-1 (SGP-1/prosaposin) in Sertoli cells.
AB  - Sulfated Glycoprotein-1 (SGP-1) is a major polypeptide secreted by rat Sertoli
      cells. Sequence analysis revealed a 70% sequence similarity with human prosaposin
      and a 80% similarity with mouse prosaposin. Both human and mouse prosaposin are
      65-70 kDa proteins cleaved in the lysosomes into four 10-15 kDa proteins
      designated saposins A, B, C and D. Lysosomal saposins function as enzymatic
      activators that promote the hydrolysis of certain glycolipids. SGP-1 (70 kDa) was
      first considered as being exclusively secreted to the extracellular space.
      However, recent immunocytochemical studies using an anti SGP-1 antibody
      demonstrated the presence of this protein in Sertoli cell lysosomes. In addition
      Sertoli cell lysosomes isolated by cellular fractionation were found to contain a
      65 kDa form of SGP-1 or lysosomal prosaposin, as well as, the 15 kDa saposins.
      Morphological and immunocytochemical evidences also indicated that both
      prosaposin and saposins may reach Sertoli cell phagosomes by lysosomal fusion.
      These phagosomes contain cytoplasmic residual bodies detached from spermatids
      during spermiation. Thus, prosaposin and their derived saposins must play a role
      in the hydrolysis of membrane glycolipids present in phagocytosed residual
      bodies. On the other hand, the function of the secreted form of SGP-1 is still
      unclear. However, SGP-1 was seen to interact with the plasma membrane of
      developing spermatids. Due to its capacity to bind certain types of gangliosides,
      SGP-1 appears to act as glycolipid transfer between Sertoli cells and the
      developing spermatids.

PMID- 8573995
TI  - The interchromatin granules.
AB  - In the present review, we report on the data obtained on the most prominent
      elements observed in the interchromatin spaces: the interchromatin granules
      (IGs). Special emphasis is placed on the recent contributions of
      immunocytochemical and in situ hybridization methods towards elucidating the
      composition and the behavior of these nuclear substructures during the cell
      cycle. The possible roles of IGs in the cell nucleus are also discussed.

PMID- 8573993
TI  - Celiprolol. An evaluation of its pharmacological properties and clinical efficacy
      in the management of hypertension and angina pectoris.
AB  - Celiprolol is a beta 1-selective adrenoceptor antagonist (beta-blocker) which
      acts as a weak agonist at beta 2-adrenoceptors. The drug demonstrates vasodilator
      properties and does not depress heart rate to the same extent as propranolol,
      atenolol or metoprolol. Celiprolol has shown equivalent antihypertensive efficacy
      to other beta-blockers, notably propranolol, atenolol, metoprolol and pindolol,
      in patients aged 18 to 75 years with mild to moderate essential hypertension. The
      drug has also shown similar antihypertensive efficacy to the angiotensin
      converting enzyme inhibitor enalapril and to combination diuretic therapy with
      hydrochlorothiazide and amiloride. Celiprolol was equally effective in adult
      patients of all ages, although no data are available for patients aged over 75
      years. Data from a small number of clinical trials indicate celiprolol to be as
      effective as both propranolol and atenolol in improving work capacity and
      reducing the frequency of anginal attacks in patients with stable effort angina.
      However, the drug has not yet been evaluated in postmyocardial infarction
      patients. Celiprolol offers advantages over other beta-blockers, including
      reduction of peripheral vascular resistance and maintenance of resting heart
      rate, cardiac output and renal perfusion. The drug is also associated with
      improvements in plasma lipid profiles and does not appear to adversely affect
      carbohydrate metabolism or lung function, although its use in patients with
      reversible obstructive pulmonary disease is not recommended. Celiprolol is
      therefore a highly cardioselective beta-blocker with ancillary characteristics
      which are potentially useful in patients with hypertension and angina complicated
      by other conditions commonly associated with advanced age. These include impaired
      glucose tolerance or diabetes mellitus, peripheral vascular disease and
      hyperlipidaemia. The drug may also be preferred to other beta-blockers in
      patients in whom a reduction in heart rate would be particularly undesirable.
      Further long term (> 12 months) clinical trials and pharmacoeconomic data are now
      required to confirm the clinical relevance of the pharmacodynamic advantages of
      celiprolol therapy.

PMID- 8573996
TI  - Experimental models for carcinogenesis in the house musk shrew, Suncus murinus,
      Insectivora.
AB  - Animal carcinogenicity studies have mainly been performed on rodents. From the
      phylogenetic point of view, animals closer to humans must be included in these
      studies. Insectivora are considered to be the most primitive placental mammals
      and much closer to the early primates than rodents. Among the insectivora, the
      house musk shrew (Suncus murinus, family Soracidae), has been bred under
      laboratory condition. This animal is small having a short life span, and a
      comparatively low incidence of spontaneous tumor provides a useful animal model
      for tumor induction studies. We have examined the carcinogenicity of several
      chemicals known to produce tumors in rodents and found shrews, in general, to be
      sensitive to these chemicals but often showed different targets compared to
      rodents, and some chemicals tested were demonstrated not to be carcinogenic. Here
      we describe the carcinogenic studies performed in our laboratory and review other
      works including the occurrence of spontaneous tumors in shrews. Shrew
      carcinogenesis may fill up the gap of knowledge existing between the rodents and
      human beings.

PMID- 8573991
TI  - ACE inhibitors. Differential use in elderly patients with hypertension.
AB  - High blood pressure (BP) in the elderly must not be ignored as a normal
      consequence of aging. The criteria for the diagnosis of hypertension and the
      necessity to treat it are the same in elderly and younger patients. The aim of
      treatment of elderly hypertensive patients is to decrease BP safely and to reduce
      risk factors associated with cerebrovascular, cardiovascular and renal morbidity
      and mortality. The treatment of elderly hypertensive patients should be adjusted
      according to the needs of the individual, based upon age, race, severity of
      hypertension, co-existing medical problems, other cardiovascular risk factors,
      target-organ damage, risk-benefit considerations and costs. In addition to the
      elevated BP, other cardiovascular risk factors include smoking, glucose
      intolerance, hyperinsulinaemia, dyslipidaemia, hypercreatininaemia, peripheral
      vascular disease, left ventricular hypertrophy, and microalbuminuria (or
      albuminuria). Thus, the choice of initial antihypertensive therapy in elderly
      hypertensive patients should be based not only on the expected response, but also
      on the effects of therapy on lipid, potassium, glucose and uric acid levels, and
      left ventricular anatomy and function. Co-existing medical conditions (such as
      asthma, diabetes mellitus, heart failure, renal failure, gout, coronary artery
      disease, hyperlipidaemia and peripheral vascular disease) are major determinants
      for the selection of antihypertensive medications. With previous therapies
      (diuretics, beta-blockers, etc.), good BP control in the elderly was associated
      with clear and statistically significant reductions in stroke-related morbidity
      and mortality, but the overall effects on cardiovascular and renal complications
      of hypertension was either more variable or less obvious. Angiotensin converting
      enzyme (ACE) inhibitors are not only efficacious antihypertensive agents in the
      elderly, but also appear promising in counteracting some of the cardiovascular
      and renal consequences of hypertension. They are well tolerated and have a
      relatively low incidence of adverse effects. ACE inhibitors possess ancillary
      characteristics that are potentially beneficial for many elderly patients,
      including reduction of left ventricular mass, lack of metabolic and lipid
      disturbances, no adverse CNS effects, no risk of induction of heart failure, and
      a low risk of orthostatic hypotension. Since ACE inhibitors may improve perfusion
      to the heart, kidney and brain, they are well worth considering for the treatment
      of elderly patients with hypertensive target organ damage, especially in patients
      with heart failure, and diabetic patients with early nephropathy.

PMID- 8573997
TI  - Morphological and histochemical changes in the liver and pancreas of gilthead,
      Sparus auratus L., induced by acute action of the anionic detergent, sodium
      dodecyl sulphate.
AB  - This paper reports the morphological and histochemical changes in the livers and
      pancreas of giltheads (Sparus auratus, L.) induced by acute action of the anionic
      detergent, sodium dodecyl sulphate (SDS). Sixty-five giltheads were exposed to
      SDS concentrations of 5, 8.5, 10 and 15 mg/l. The surface tension induced at each
      concentration was determined and the LC50 calculated. Morphological changes
      dependent on detergent concentrations and length of exposure were seen.
      Histochemical techniques showed alterations in carbohydrates and proteins, which
      may interfere with liver and pancreas function.

PMID- 8573998
TI  - Characteristics of MHC antigen expression and tumor-infiltrating mononuclear
      cells in renal cell adenomas and carcinomas.
AB  - We compared the expression of major histocompatibility complex (MHC; HLA class I
      and II) antigens and the presence of tumor-infiltrating mononuclear cells
      presenting S100 protein (S100), CD68 antigen, or CD45RO antigen in formalin
      fixed, paraffin-embedded tissue sections of 10 renal cell carcinomas and 9 renal
      cell adenomas using immunohistochemistry. The expression of beta 2-microglobulin
      (B2MG) as an HLA class I antigen in all 10 cases (100%) and that of HLA-DR/alpha
      as an HLA class II antigen in 7 of 10 cases (70%) of carcinoma was stronger than
      that in the adjacent proximal convoluted tubule, but was respectively not
      different to weaker in 8 of 9 cases and not different to markedly weaker in all
      cases of adenoma. Furthermore, there was comparatively dense infiltration by
      S100(+) antigen-presenting cells in the carcinomas, but almost none in the
      adenomas and generally dense infiltration by CD45RO(+) T cells and CD68(+)
      macrophages in the carcinomas, but little to none in the adenomas. We concluded
      that the generally enhanced expression of MHC antigens in carcinomas must be an
      immunophenotypic deviation from not only the adjacent proximal convoluted tubule
      but also adenomas, and that the predominant infiltration of antigen-presenting
      cells, T cells and macrophages in the carcinomas, but not in the adenomas,
      reflects the anti-cancer immune reaction.

PMID- 8573999
TI  - The density and distribution of follicular dendritic cells in rat popliteal lymph
      nodes: a decrease in their density and a change in their distribution after
      stimulation.
AB  - To determine whether follicular dendritic cells (FDCs) increase after
      stimulation, and also to confirm the widely accepted finding that the density of
      FDCs in the light zone is higher than that in the dark zone, we examined the
      density of FDCs in lymph follicles of rat popliteal lymph nodes. Rats aged five
      weeks were stimulated by injection of sheep erythrocytes, and then examined 10
      days later. Unstimulated rats were also examined. After embedding in paraffin,
      the removed lymph nodes were immunostained with anti-S-100 protein antibody as a
      marker of rat FDCs. The density of FDCs was determined by measuring the area of
      the lymph follicle and counting the number of S-100 protein-positive cells within
      it. The density of FDCs in the lymph follicles of stimulated rats was found to be
      significantly lower than in 5-week-old and unstimulated rats. The density of FDCs
      in the light zone was similar to that in the dark zone when germinal center
      bordering cells (GCBCs), distributed at the border between the dark zone and the
      adjacent corona, were counted as FDCs. We conclude that the density of FDCs in
      lymph follicles decreases after stimulation, and suggest that FDCs have no or
      only very slight proliferative activity under normal conditions. Investigators
      may need to consider GCBCs in order to understand how FDCs differentiate.

PMID- 8574000
TI  - Use of a fibroblastic matrix improves the results of mesothelial-cell seeding on
      vascular prostheses of polytetrafluoroethylene.
AB  - Mesothelial cells (MC) obtained from the human omentum are a good alternative to
      the use of endothelial cells (EC) as a covering for vascular prostheses of
      polytetrafluoroethylene (PTFE), given the antithrombogenic properties and good
      behavior in vitro of mesothelial cells. We studied the behaviour of mesothelial
      cells seeded on PTFE prostheses with an interposed fibroblastic matrix for
      seeding. The mesothelial cells were extracted from 30-40 g fragments of human
      omentum by enzymatic digestion with collagenase. The cells extracted were seeded
      onto small disks of PTFE to which a matrix composed of fibroblastic cells had
      been fixed with 5% glycerol after the fibroblasts reached convergence.
      Interposition of a fibroblastic matrix fixed with glycerol notably improved the
      adherence of the seeded mesothelial cells and the stability and durability of the
      cell layer formed on the prosthetic surface. The effectiveness of seeding
      mesothelial cells was confirmed by labelling the cells with 111In-oxine. This
      showed that once the cell layer had formed (24 h after seeding), the fibroblastic
      matrix favoured the maintenance of a stable layer of mesothelial cells 4 hours
      after uptake of the radioactive substance.

PMID- 8574001
TI  - A genetic model for undifferentiated cell tumor formation: similar tumors formed
      by different cell lines transformed by the E1A oncogene.
AB  - The activation of oncogenes and the mutation/deletion of suppressor genes may be
      involved in tumor heterogeneity. In an attempt to study tumor heterogeneity, we
      transformed cell lines from epithelial (PAM 212), mesenchymal (NIH-3T3), or
      melanocytic origin (L-BIOBR) with the wild type E1a oncogene. To make the cell
      lines tumorigenic, cells were infected with Harvey sarcoma virus carrying the v-H
      ras oncogene. The transformed cells were injected into nude mice and the tumors
      studied by optical and electron microscopy. The tumors formed by v-H-ras
      transformed cells consisted of epitheliod melanomas, spindle cells sarcomas and
      poorly-differentiated carcinomas, depending on the cell of origin. In contrast,
      the tumors obtained from cells also carrying the E1a oncogene showed a
      predominant small and undifferentiated cell pattern regardless of the cell of
      origin. We conclude that the E1a oncogene products induce a negative control of
      differentiation, independent of the cell type, and that tumors formed by cells
      carrying the E1a oncogene display an undifferentiated cell pattern.

PMID- 8574002
TI  - Morphological changes of myoepithelial cells of mouse lacrimal glands during
      postnatal development.
AB  - To reveal the correlation between myoepithelial cell configuration and size/shape
      of glandular endpieces (acini), we observed postnatal developmental changes of
      myoepithelial cells in the lacrimal glands of mice. Glandular and myoepithelial
      cells were examined in paraffin sections and in isolated acini. In newborns,
      rudiments of acini showed no clear lumina and glandular cells had few secretory
      granules. There were no myoepithelial cells with actin. At 3 days after birth,
      some rudiments showed lumina; however, secretory granules were not salient. Round
      cells in the periphery of the acini showed immunoreactivity for actin. In 1-week
      old mice, glandular cells were polarized: luminal cytoplasm contained some
      secretory granules, and nuclei were located basally. Most myoepithelial cells
      were flattened and sometimes projected thin processes in various directions. At 2
      weeks, the glandular cells increased their size and contained numerous secretory
      granules, and the myoepithelial cells were almost stellate. In 4-8 week-old mice,
      acini increased their size, and myoepithelial cells were very thin and processes
      were prolonged in length and increased in number. During postnatal development,
      their distribution of myoepithelial cells was more scarce, while the size of
      acini increased. This reciprocal relation of myoepithelial cell distribution and
      acinar size may indicate that the changes of myoepithelial cell configurations
      depend on the change of acinus size.

PMID- 8574004
TI  - An ultrastructural study of neuronal changes in dorsal root ganglia (DRG) of rats
      after chronic cisplatin administrations.
AB  - In humans, the main dose-limiting side-effect of cisplatin (CDDP) treatment is a
      peripheral sensory neuropathy secondary to dorsal root ganglion (DRG) neuron
      involvement. To investigate further for neuronal alterations responsible for CDDP
      neurotoxicity we undertook the present experimental ultrastructural study, based
      on observations of 3 different groups of rats (6 animals in each group). Group A
      rats were treated with 1 mg/kg weekly for 9 weeks; Group B with 2 mg/kg weekly
      for 9 weeks; and group C rats served as untreated controls. At the end of the
      experiment, rats were perfused with 3% glutaraldehyde and lumbar DRGs were
      prepared for electron microscopic observations. In CDDP-treated rats somatic,
      nuclear and, above all, nucleolar size was reduced. Ultrastructurally, the
      nucleolus was the most affected structure. Nucleolar alterations were quantified
      morphometrically. Less marked changes were seen in the nucleus and in the RER and
      Golgi apparatus of the cytoplasm. The number of lysosomes and lipofuscins was
      greatly increased in CDDP-treated rats. The ultrastructural alterations observed
      in CDDP rats suggest that CDDP may be neurotoxic due to a reduction in protein
      synthesis. This assumption would explain why cells such as neurons, which are non
      replicating, but which have a high rate of protein synthesis, may be the target
      of the neurotoxic action of CDDP. The lack of an efficient blood/nerve barrier in
      the DRG explains the involvement of this particular type of neuron.

PMID- 8574003
TI  - Characteristics of distribution of peptide-containing nerve fibres in the
      atrioventricular valves of the rat.
AB  - The distribution of vasoactive intestinal polypeptide-, neuropeptide Y-, and
      calcitonin gene-related peptide-immunoreactive nerve fibres was investigated in
      the atrioventricular valves of the rat. These nerve fibres were visualized by
      immunostaining of whole-mount preparations by the avidin-biotin-peroxidase
      complex method. Vasoactive intestinal polypeptide-immunoreactive nerve fibres
      were observed mainly in the anterior cusp of the mitral valve and, to a lesser
      extent, in the medial cusp of the tricuspid valve. Numerous neuropeptide Y
      immunoreactive nerve fibres were found covering all of the cusps. Both types of
      peptidergic nerve fibre formed dense networks that consisted of interlacing and
      anastomosing nerve fibres. Calcitonin gene-related peptide-immunoreactive nerve
      fibres were seen in every cusp, but did not form a fine network. These results
      provide detailed anatomical information for evaluation of the possible roles of
      each type of peptide-containing nerve fibre in the function of atrioventricular
      valves.

PMID- 8574005
TI  - Central projections from the goldfish pineal organ traced by HRP
      immunocytochemistry.
AB  - Pineal efferent projections have been traced in the brain of the goldfish
      (Carassius auratus) by administration of a concentrated solution of horseradish
      peroxidase onto the pineal organ. After different survival times, fish were
      sacrificed and the administered peroxidase was revealed by immunocytochemistry on
      paraffin sections using an anti-horseradish peroxidase antiserum. Immunoreactive
      fibres were seen in the anterior hypothalamus, habenula, dorsal thalamus, ventral
      thalamus, optic tectum, torus longitudinalis, area pretectalis, torus
      semicircularis and dorsal tegmentum. No immunoreactive cell bodies were
      visualized in the central nervous system, thus suggesting the absence of central
      pinealopetal innervation. Since all areas showing pineal labelled fibres are also
      known to receive retinal inputs, it can be suggested that an overlapping of
      information from retinal and extraretinal photoreceptors may be important to
      processes depending on photic stimulation such as entrainment of circadian
      rhythms or photoneuroendocrine responses.

PMID- 8574006
TI  - Scanning electron microscopy of capsaicin-pretreated trachea in the rat during
      postnatal development.
AB  - The morphological changes of the tracheal surface were studied in neonatally
      capsaicin-pretreated rats by scanning electron microscopy. One week after
      neonatal capsaicin treatment, a sparse number of ciliated cells were dispersed
      among the microvilli-covered goblet cells similar to those of the sham-operated
      rats. Potential ciliated cells (progenitor cells) possessed a few long cilia and
      many short cilia. The ciliated cells possessed cilia with a smooth surface and a
      blunt end similar to that of the sham-operated rats. Two weeks after neonatal
      capsaicin treatment, numerous ciliated cells frequently in clusters were located
      among large patches of microvilli-covered goblet cells similar to those of sham
      operated rats. Furthermore, the blunt ends of cilia and microvilli contained
      short star-shaped protrusions extending into the lumen of the trachea. One month
      after neonatal capsaicin treatment, the star-shaped protrusions became longer,
      and more irregular than those of sham-operated rats. The short cilia of the
      potential ciliated cells (progenitor cells) also became blunt and irregular in
      shape. The star-shaped protrusions of the microvilli of the goblet cells became
      larger and thicker than those observed at two weeks following capsaicin
      pretreatment. Two months after neonatal capsaicin treatment, the tracheal surface
      was lined with a much greater population of the ciliated cells than that at one
      month. A striking characteristic at this age was that globular mucin-containing
      secretory products were trapped within the cilia of the ciliated cells. The
      results of this study suggest that mucus secretion is probably blocked by the
      capsaicin-pretreatment. Furthermore, the star-shaped protrusions of cilia and
      microvilli may indicate that the mucociliary clearance mechanism is interfered
      with by the capsaicin-pretreatment.

PMID- 8574007
TI  - Ultrastructural study of a special type of ependymal cell at paraventricular
      level of the golden hamster third ventricle.
AB  - The present paper describes the presence of a special cell located in the
      ependymal wall at the level of the paraventricular nucleus. At this level,
      ultrastructural observation of these ependymal cells, unlike most other mammalian
      species, shows the presence of nucleolus-like bodies in their cytoplasm and
      occasionally basal processes. These processes appear perpendicular to the
      ependymal surface and end in contact with the basal membrane of hypothalamic
      capillaries. Mitochondria, endoplasmic reticulum and numerous filaments are
      present in the basal processes. Nucleolus-like bodies or nematosomes consist of
      round or ovoid unbound masses of granular appearing material of variable density
      located in the apical cytoplasm of the cells. Some of their ultrastructural
      characteristics are similar to other ependymal specialized cells which are
      classically termed tanycytes. These findings point out the possibility that those
      special cells may also be implicated in a ventricle-blood vessel communication.

PMID- 8574008
TI  - Effects of melatonin, testosterone and the two hormones administered in parallel
      on ventral prostate of the rat treated with stilbestrol in the first day of life.
AB  - Effects of melatonin, testosterone and the two hormones administered in parallel
      on ventral prostate were examined in the rats treated with estrogens in the first
      day of life. Thirty-nine-day long hormonal stimulation with melatonin,
      testosterone or the two hormones in parallel was started in rats aged 20, 28, 35
      or 45 days. A single dose of estrogens led to atrophy of ventral prostate when
      the animals reached maturity, which was associated with high LH levels and low
      testosterone levels in the serum. Melatonin accentuated estrogen-induced changes
      in prostate morphology of ventral prostate while initemporal administration of
      melatonin and testosterone led to a resultant effect of testosterone-induced
      stimulation and melatonin-induced inhibition.

PMID- 8574009
TI  - Age and experimental obstructive emphysema. A morphometrical study on the rat.
AB  - Age, as a risk factor in the development of experimental obstructive emphysema,
      is proposed as the hypothesis of this study. Ninety-two Wistar rats were
      organized into two age groups: adult (16 weeks) and middle-aged (56 weeks). Each
      age group was subdivided into three groups: a control group, consisting of
      unmanipulated animals; a "cannula" group consisting of animals into whose trachea
      a cannula was implanted; and a "valve" group, consisting of animals into whose
      trachea a valve had been implanted. The survival was one month. A
      histomorphometric study was performed on the lungs and the results were compared
      statistically. Throughout the experiment the amount of food consumed by each
      animal and the variations in weight were monitored. After sacrifice, the lungs
      were processed for light microscopy. Thirteen histomorphometric variables were
      quantified and subsequently systematized into three groups: those which
      quantified the size of the distal airspace ("area of the alveolar section",
      "alveolar chord" and "mean linear intercept"): those which quantified the tissue
      ("wall thickness", "tissue density", "internal perimeter of each alveolar
      section", "internal alveolar perimeter per field" and "alveolar section/section
      perimeter"); and those which quantified the elastic fibre ("elastic fibre area",
      "elastic fibre perimeter", "elastic fibre area/elastic fibre perimeter", "elastic
      fibre density" and "elastic fibre density per tissue density"). The results were
      compared statistically and the sensitivity, specificity and misclassification
      indices were calculated, as well as the attributable and relative risk. From the
      results, it was observed that, in general, the animals of the valve and cannula
      groups in both age groups displayed a decrease in food intake and a body weight
      loss. The middle-aged animals were the only group which displayed significant
      differences in all the morphometric variables except wall thickness, when the
      cannula and valve groups were compared with the control group. In both the
      cannula and valve groups, the values of the variables which quantified the distal
      airspace increased, while the values of the variables which quantified the lung
      tissue and the elastic fibre decreased. In the manipulated middle-aged group, the
      attributable risk of developing emphysema was 56.66% and the relative risk 5.55;
      in the group of manipulated adult animals, the attributable risk was 23.55% and
      the relative risk 1.66. The results of this study lead us to propose that the
      middle-aged rats with experimental airflow obstruction displayed a greater risk
      of developing emphysema than the adult rats which were subjected to the same
      procedure.

PMID- 8574010
TI  - The thyroid gland of Callithrix jacchus in organ culture.
AB  - Thyroid glands from 7 marmosets (Callithrix jacchus) of different age groups
      (newborn, 2 weeks, 2, 7, 8 and 11 months, and 8 years) were grown as organ
      culture according to Trowell at the medium/air interphase for 3 to 30 days. The
      morphology of thyroid tissue was well preserved until the end of the culture
      period. Necroses were only occasionally seen in connective tissue. In contrast to
      the in vivo situation, the number of lysosome-like inclusions changed
      considerably and cell-cell contacts became loose. After the addition of TSH the
      number of apical microvilli, apical granules and coated vesicles rose. The basal
      surface of follicle cells enlarged due to the formation of processes or ridges
      and invaginations. Mitosis could be observed. These findings show that, using the
      Trowell culture technique, thyroid tissue can be grown for up to 4 weeks without
      showing distinct changes in its morphology. Its responsiveness to the application
      of TSH is maintained in vitro. Hence, this technique is suitable also for long
      term endocrinological, pharmacological and toxicological investigations.

PMID- 8574011
TI  - Effects of progesterone on the ultrastructure of the golden hamster parathyroid
      gland.
AB  - The ultrastructure of the parathyroid glands in golden hamsters after
      administration of progesterone was investigated. In the parathyroid glands of the
      female hamsters after administration of progesterone, the mean serum calcium
      concentration was significantly higher when compared to that of the control
      hamsters. In the male experimental hamsters, the percentage area occupied by
      Golgi complexes and lipid droplets was significantly increased when compared to
      that of the control hamsters, respectively. In the female hamsters after
      administration of progesterone, the percentage area occupied by large vacuolar
      bodies was significantly decreased when compared to that of the control hamsters.
      In the male and female experimental hamsters, the mean number of secretory
      granules per 100 microns2 of cytoplasm showed a significant increase compared
      with that of the male and female control hamsters, respectively. These findings
      suggest that the secretory activity of the parathyroid glands may be stimulated
      in response to hypocalcemia induced by progesterone.

PMID- 8574012
TI  - Blood-retinal barrier breakdown in retinitis pigmentosa: light and electron
      microscopic immunolocalization.
AB  - Macular edema can contribute to visual loss in the retinitis pigmentosa (RP), but
      the sites and mechanism of blood-retinal barrier (BRB) breakdown leading to
      macular edema are not known. An understanding of the mechanisms involved could
      lead to the design of effective pharmacologic therapy to prevent or minimize
      macular edema in RP. To investigate this problem, immunohistochemical staining
      for albumin was performed on paraffin sections of 22 normal and 29 RP-affected
      eyes. Specimens were graded for extent of albumin extravasation in different
      regions of the retina, optic nerve head, ciliary body, and iris. Electron
      microscopic immunocytochemical staining for albumin was performed on an
      additional 6 normal and 9 RP-affected eyes. Two-thirds of the eyes from patients
      with RP and no other ocular disorders demonstrated extravascular albumin in the
      inner portion of the posterior retina. This was evident even in the absence of
      cystoid macular edema (CME), but eyes that had CME showed extensive BRB failure.
      In some cases, passage of albumin from the choroid to the retina was prevented
      even in the absence of the retinal pigment epithelium (RPE). Electron microscopic
      immunocytochemistry revealed that albumin permeated retinal vascular endothelial
      cells and RPE cells that showed degenerative changes in RP.

PMID- 8574013
TI  - Copper/zinc and manganese superoxide dismutase immunoreactivity in hepatic iron
      overload diseases.
AB  - Iron overload to the liver induces hepatic injury, eventually ending up with
      liver fibrosis or cirrhosis. Pathogenic mechanisms involved in liver damage are
      only partially known, but there is evidence for an important role of iron-induced
      reactive oxygen species. We have, therefore, analyzed the immunohistochemical
      reactivity for two major free radical scavengers, copper/zinc and manganese
      superoxide dismutase (Cu/Zn- and Mn-SOD's) in three situations of hepatic iron
      overload, and compared enzyme patterns with grades of iron deposition, grades of
      fibrosis, and levels of microphotometrically measured type IV collagen
      immunoreactivity. Cu/Zn- and Mn-SOD reactivity was detectable in hepatocytes with
      a heavy and a low iron burden, but Cu/Zn-SOD staining was more intense than that
      of Mn-SOD in the three groups analysed. There was trend for microphotometrically
      measured type IV collagen levels to increase with the amount of iron, and
      increased collagen IV was correlated with higher grades of Cu/Zn-SOD, but not of
      Mn-SOD, reactivity. The findings suggest that the two SOD's may be differentially
      expressed in states of hepatic iron overload, and that low expression of the
      inducible radical scavenger, Mn-SOD, may play a role in chronic iron toxicity.

PMID- 8574014
TI  - Contribution of the proximal and distal nerve stumps to peripheral nerve
      regeneration in silicone chambers.
AB  - The specific contribution of the proximal and distal nerve stumps across an 8 mm
      gap within silicone chamber regeneration models was studied. For this, proximal
      and distal (Group A), distal and distal (Group B) and proximal and proximal
      (Group C) nerve stumps were placed in opposite ends of silicone chambers. In all
      the groups, a tissue cable forms between the nerve stumps, demonstrating that,
      without distinction, proximal or distal stumps can stimulate the growth of other
      proximal or distal stumps. Furthermore, in Group B, the newly formed pseudo
      nerve, in the absence of regenerating axons, contains a number of Schwann cells
      significantly similar to Group A, which confirms that proliferation and migration
      of Schwann cells do not require axonal presence or contact. Likewise, the
      findings demonstrate that, with the exception of the axons, the distal stump
      contributes to the peripheral nerve regeneration in the same way as the proximal
      stump. Finally, when proximal stumps are placed in both the opposite ends of the
      silicone chamber, Schwann cells and regenerating axons grow into the chamber gap
      from both inserts, and myelination also proceeds from both ends to the centre of
      the chambers.

PMID- 8574015
TI  - Substance P: a neurotransmitter of amacrine and ganglion cells in the vertebrate
      retina.
AB  - A short history and summary of the occurrence of substance P in the vertebrate
      body is presented. Substance P is now generally accepted to be a neurotransmitter
      and can be visualized by immunocytochemistry to occur in various nerve cells in
      the CNS. In the retina, substance P-immunoreactivity (SP-IR) occurs in amacrine
      cell populations in all the species so far studied. In some vertebrates retinas
      SP is also apparent in one or more ganglion cell types. Anatomical investigations
      have revealed the morphology and connectivity of SP-IR amacrine cells: they
      branch in several strata of the inner plexiform layer receiving input from
      bipolar and amacrine cells and making synapses upon bipolar and ganglion cells.
      Most commonly SP-IR amacrines emit axon-like process that pass to both the outer
      plexiform layer and the ganglion cell and nerve fiber layers. These processes
      often end upon the retinal vasculature. SP-IR ganglion cells have been described
      in turtle, rabbit and human retinas. In turtle, intracellular dye injection has
      revealed the morphology of one type of SP-IR ganglion cell as being a large-field
      monostratified cell with a branches in the outer stratum of the inner plexiform
      layer. It may correspond to a "Dogiel cell" type. Intracellular investigation of
      SP-IR amacrine cells in turtle reveal their physiological responses to be ON-OFF
      in nature with some color-coding characteristics. In general SP acts as an
      excitatory neurotransmitter raising the spontaneous activity level of ganglion
      cell responses. The SP-IR ganglion cell is an OFF-center unit in the turtle
      retina and may be driven in the center of its receptive field by luminosity
      bipolar cells and in its surround by amacrine cells with color-opponent
      properties.

PMID- 8574016
TI  - Neurofibrillary pathology and aluminum in Alzheimer's disease.
AB  - Since the first reports of aluminum-induced neurofibrillary degeneration in
      experimental animals, extensive studies have been performed to clarify the role
      played by aluminum in the pathogenesis of Alzheimer's disease (AD). Additional
      evidence implicating aluminum in AD includes elevated levels of aluminum in the
      AD brain, epidemiological data linking aluminum exposure to AD, and interactions
      between aluminum and protein components in the pathological lesions of AD, i.e.,
      neurofibrillary tangles (NFTs) and senile plaques (SPs). As most of this evidence
      is circumstantial and some of it is not consistent in all reports, the role of
      aluminum in the pathogenesis of AD has remained controversial. However, the
      interaction of aluminum with altered forms of tau in the paired helical filaments
      (PHFs) of neurofibrillary lesions is highly likely to contribute to the formation
      of NFTs because (1) aluminum and abnormally phosphorylated tau (known as PHF tau)
      are colocalized in NFTs, and (2) aluminum is known to preferentially interact
      with such phosphorylated proteins. Recently, we demonstrated that aluminum binds
      selectively to PHF tau, induces PHF tau to aggregate, and retards the in vivo
      proteolysis of PHF tau. These data suggest that aluminum could serve as cofactor
      in the formation of NFTs by interacting with PHF tau. This review summarizes
      current understanding of how aluminum might contribute to the formation of
      neurofibrillary lesions from PHF tau in neurons of the AD brain.

PMID- 8574017
TI  - The glucose-6-phosphatase system in human development.
AB  - The classical role of glucose-6-phosphatase in liver and kidney is the production
      of glucose for release into blood. In liver, glucose-6-phosphatase catalyses the
      terminal step of glycogenolysis and gluconeogenesis. Abnormally low hepatic
      glucose-6-phosphatase activity is found in human genetic deficiencies i.e.
      glycogen storage disease type I and in cases of developmental delay, found
      predominantly in preterm infants. In contrast, abnormally high liver glucose-6
      phosphatase occurs in poorly controlled or untreated diabetes mellitus. Hepatic
      glucose-6-phosphatase is an integral endoplasmic reticulum (and nuclear membrane)
      protein and it is part of a multicomponent system. Its active site is situated
      inside the lumen of the endoplasmic reticulum and transport proteins are needed
      to allow its substrates glucose-6-phosphate (and pyrophosphate) and its products
      phosphate and glucose to cross the endoplasmic reticulum membrane. In addition, a
      calcium binding protein is also associated with the glucose-6-phosphatase enzyme.
      Immunohistochemical studies, in combination with image analysis, have shown that
      glucose-6-phosphatase is present in liver and kidney and also in specific cell
      types in a variety of human tissues, for example Leydig cells in the testis and
      some astrocytes in the brain. Where practicable, enzymatic analysis, direct
      transport assays and/or immunological detection of the endoplasmic reticulum
      glucose and phosphate transport proteins have been used to demonstrate the
      presence and activity of the whole glucose-6-phosphatase system. The distribution
      of the human glucose-6-phosphatase system changes dramatically during development
      with a different spatial and temporal pattern in each tissue. The most unexpected
      localization was in circulating, predominantly nucleated, embryonic and early
      fetal red blood cells.

PMID- 8574018
TI  - The pathological changes in peripheral organs of scrapie-infected animals.
AB  - Scrapie is an unconventional neurodegenerative disease in sheep and goats that
      has been known in Europe for over 260 Years. The scrapie agents affect the brain
      and are transmissible from animal to animal. Key features of scrapie infections
      are abnormal behavior and deficits in motor function. These clinical findings can
      be related to the damage found in the central nervous system. In some scrapie
      strain-host model systems there are other manifestations of disease that appear
      to be related to pathological changes found in the peripheral organs, especially
      in the endocrine organs such as pituitary, adrenal glands, the islet of
      Langerhans and ovary. In those model systems in which extensive histopathological
      changes have been seen in peripheral organs, the titers of scrapie infectivity
      and the levels of the scrapie specific protein, PrPSc, are relatively low in the
      affected organs. These data suggest but do not prove that changes in peripheral
      organs are secondary to the scrapie-induced neurodegeneration that is occurring
      in the brain. In some scrapie strain-host combinations, obesity and aberrant
      glucose metabolism are seen in the preclinical and clinical phases of the
      incubation period. There appear to be two pathways that lead to these particular
      clinical manifestations. In SJL mice infected by the ME7 or 22L strains of mouse
      adapted scrapie and in some scrapie-infected sheep, the mechanism is related to
      changes induced in the hypothalamic-pituitary-adrenal axis. The other pathway is
      exemplified by hamsters infected with two hamster-adapted scrapie strains, 139H
      and 22CH; it appears that lesions found in the hypothalamic-islets of Langerhans
      axis are critical. A number of reviews on the pathological changes in the central
      nervous system have been published and therefore, in this review article, we
      focus on the gross and histopathological changes in peripheral organs in several
      scrapie strain-host combinations. The changes induced in peripheral organs in a
      number of scrapie strain-host combinations expand the number of diseases in which
      the unconventional slow infections could serve as a model. Further work in this
      area could help us to understand the mechanisms and pathways of the pathological
      changes found in the peripheral organs of the scrapie-infected animals.

PMID- 8574019
TI  - Video assisted coronary bypass surgery.
AB  - An alternative way to revascularize coronary vessels is described, using arterial
      conduits without extracorporeal circulation. The heart is exposed via a small
      thoracotomy over the fifth left intercostal space. A thoracoscope is introduced
      into the thorax, to assist in the harvesting of the left internal mammary artery
      (LIMA). In selected patients with two or three vessel disease, the same procedure
      can be achieved on the right side, harvesting the right internal mammary artery
      to revascularize the right coronary artery. The gastroepiploic artery can be
      easily reached and used to revascularize the posterior descending artery, through
      a mini-subxiphoid median laparotomy. This technique was used to revascularize 30
      patients from April 1994 to June 1995. All received a LIMA graft to the left
      anterior descending artery, and two had a free radial artery graft from the LIMA,
      sequentially bypassing the diagonal and obtuse marginal branches. There was
      neither perioperative mortality nor morbidity myocardial infarction. Fifteen
      patients were restudied angiographically before discharge. Average hospital stay
      was 43 +/- 11 hours.

PMID- 8574020
TI  - Surgical management of instrumentation-induced coronary artery dissection.
AB  - The mechanism of instrument-induced coronary artery dissections (IICDs) is
      briefly presented. Depending on the coronary anatomy, three different situations
      that may occur are distinguished: (1) major coronary branches between the site of
      dissection and planned anastomosis; (2) no important collaterals at the same
      location; and (3) perforation of the coronary artery. Surgical methods applicable
      to each for the correction of these situations is presented.

PMID- 8574021
TI  - Advantages of delayed sternal closure in cardiac-compromised adult patients.
AB  - Severe hemodynamic dysfunction may follow closure of the median sternotomy in
      patients with myocardial edema, cardiac dilatation, postcardiotomy shock, or
      raised end-expiratory alveolar pressure. Open sternotomy and delayed sternal
      closure (DSC) is a well described adjunct in complicated cardiac operations,
      which is more widely applied in neonates. In this article we report our results
      in using open sternotomy in eight adult patients from January 1994 to February
      1995 (excluding patients who needed ventricular assistance devices [VADs]). Three
      patients died in hospital: 1 case of multiorgan failure; 1 cases of refractory
      low cardiac output syndrome; and 1 case of respiratory distress syndrome. Our
      experience confirms that DSC is an effective means of dealing with postoperative
      hemodynamic impairment. Furthermore, this technique may represent an intermediate
      step between intraaortic balloon counterpulsation and VADs and should be given a
      role in the prophylaxis of low postoperative cardiac output and multiorgan
      failure, particularly when contraindications to VAD exist.

PMID- 8574022
TI  - Poststernotomy mediastinitis treated by transposition of the greater omentum.
AB  - Due to its anatomical structure and physiological properties, omental tissue has
      proven to be beneficial when transposed to the thorax to treat severe mediastinal
      infections. Between April 1987 and July 1994, 17,005 open heart operations were
      performed at our institution. One hundred and forty patients who developed
      mediastinitis or serious wound infections postoperatively were treated by
      transposition of the greater omentum into the retrosternal space. These patients
      were compared with a control group of 100 patients operated in the same period,
      who did not develop infectious complications postoperatively. Significant
      differences were found in several risk factors, such as obesity, type, and
      duration of primary operation, ejection fraction < 30% (< 0.01), as well as the
      incidence of low cardiac output syndrome treated by insertion of an intra-aortic
      balloon pump (p < 0.05). However, no significant differences were observed in
      factors such as diabetes mellitus, emergency operation, reoperation, degree of
      postoperative bleeding, and duration of aortic cross-clamp time. The mortality of
      mediastinitis largely depended on the type of primary operation. It was 19.2% in
      patients who underwent coronary surgery, and 52.2% in patients who underwent
      transplantation (overall mortality 35.7%). Only in 2% of the patients did we find
      complications related to the creation of the omental pedicle and its
      translocation. Today, serious disturbances in sternal wound healing, especially
      involving mediastinitis, are rare complications in cardiac surgery. Nevertheless,
      they continue to be associated with high mortality and prolonged hospitalization.

PMID- 8574023
TI  - Nonischemic ventricular tachycardia: surgical or medical treatment?
AB  - Fifty-two consecutive patients with nonischemic ventricular tachycardia (VT) were
      seen between 1985 and 1991. Twenty-two patients underwent surgery, while in the
      remaining 30, the VT was well controlled on medication. In the surgical group,
      arrhythmogenic right ventricular dysplasia (ARVD) was the cause of VT in 12
      patients, cardiomyopathy (CM) in 6, posttetralogy of Fallot repair in 2,
      myocarditis in 1, and myocardial hamartoma in 1. The mean number of drugs tried
      and found ineffective was 5.5. There were three early deaths; 13 patients are
      symptom-free without taking any medication. In the medical group, the pathology
      associated with the VT was myocarditis in 2 patients, CM in 11, and ARVD in 2. In
      ten patients, VT appeared idiopathic, 1 was exercise-induced, 3 were
      catecholamine sensitive, and 1 presented with long QT syndrome. Beta blockers
      controlled the symptoms in 43% of the patients, amiodarone in 20%, and flecainide
      in 17%. The mortality was higher in the surgical group, but 95% of them are VT
      free, compared with those on medical treatment (55%) over the last 8 years'
      follow-up. In conclusion, the nonischemic VT is a serious condition. Medical
      therapy is usually effective, but if it fails, VT surgery should be considered.

PMID- 8574024
TI  - Chronic changes of end-systolic pressure-volume relationship after regional
      myocardial infarction.
AB  - The chronic changes of the end-systolic pressure-volume relationship (ESPVR)
      after regional myocardial infarction were evaluated in a sheep model. Pressure
      volume area (PVA) obtained from the pressure-volume diagram and left ventricular
      oxygen consumption (LVO2) were studied. The regional myocardial infarction was
      created by ligating distal branches of the left coronary artery. ESPVR was
      obtained using a conductance catheter during transient inferior vena cava
      occlusion. Measurements were performed at baseline (n = 13), 1 hour (n = 8), 3
      months (n = 9), and 6 months (n = 4) after infarction. Ees, the slope of the
      ESPVR did not change at 1 hour after infarction and remained the same at 3-month
      and 6-month measurements (baseline 2.26 +/- 1.24 mmHg/mL, 1 hour 2.71 +/- 1.06, 3
      months 3.46 +/- 1.51, 6 months 2.45 +/- 0.64, NS). Because of the ventricular
      dilatation, which was demonstrated as an increase in changes of end-systolic
      volume (Ves) correlating with the time course after infarction (y = -3.21 +
      0.12x, r = 0.454, p < 0.05), V0, the volume intercept of the ESPVR increased at 1
      hour after the infarction, and showed a tendency to increase at 3 months and 6
      months after the infarction (baseline -18.0 +/- 22.5 mL; 1 hour -0.9 +/- 11.6; 3
      months 5.4 +/- 10.9, 6 months 9.2 +/- 23.1, baseline vs 3 months p < 0.05,
      baseline vs 6 months p < 0.05). PVA and LVO2 were unchanged over time after
      infarction (PVA: baseline 2097 +/- 1526 mmHg/mL per 100 g-1; 1 hour 1771 +/- 699;
      3 months 2483 +/- 1086; 6 months 1,608 +/- 1,010, NS), (LVO2: baseline 40.6 +/-
      13.1 x 10(-3) mL/100 g-1 per beat-1; 1 hour 42.9 +/- 9.7; 3 months 35.0 +/- 8.6;
      6 months 31.2 +/- 18.1, NS). Chronic regional infarction in the sheep model did
      not affect Ees over 6 months, but significantly increased V0 after the increase
      in the acute phase. PVA and LVO2 were not affected by this regional infarction
      either acutely or over 6 months.

PMID- 8574026
TI  - Canine skeletal muscle ventricles: functional assessment using the pressure
      volume plane.
AB  - In five dogs, skeletal muscle ventricles (SMVs) were constructed from the
      latissimus dorsi muscle, and placed within the thoracic cavity. After a 3-week
      delay period, SMVs were electrically preconditioned with 2-Hz continuous
      stimulation for 6 weeks. At a second procedure, SMVs were connected to a mock
      circulation system, and performance was evaluated according to pressure-volume
      relationships at three different SMV contraction rates (33, 54, and 97 per min)
      and three stimulation protocols (25, 43, and 85 Hz) under varying loading
      conditions. Under appropriate conditions of afterload, the end-diastolic pressure
      volume relation of SMVs was comparable with that of the cardiac ventricles,
      although SMVs were less compliant. At higher burst stimulation frequencies, SMV
      compliance was increased. Compliance was not affected by varying the rate of SMV
      contraction. End-systolic elastance, a reflection of contractility, appeared to
      be constant for each SMV, in contrast to cardiac ventricles, and was not
      influenced by changes in burst stimulation frequency or contraction rate. In this
      study, SMVs were capable of a level of stroke work 180% of that of the native
      right ventricle (RV) at rest (0.397 +/- 0.047 x 10(6) ergs) and 37% of that of
      the left ventricle (LV) at rest (0.298 +/- 0.61 x 10(6) ergs), at 33 contractions
      per minute (CPM), 25-Hz burst frequency, and physiological preload, but this
      level could not be sustained at higher contraction rates. Nevertheless, power
      output (SMV stroke work x contraction rate) was maximal at 97 CPM. These findings
      demonstrate important function differences between pumping chambers constructed
      from conditioned skeletal muscle, and those composed of cardiac muscle, which
      must be considered when using skeletal muscle ventricles for cardiac support or
      replacement.

PMID- 8574027
TI  - Risk stratification in cardiac surgery: is it worthwhile?
AB  - Outcome analysis of many surgical procedures has become increasingly important to
      surgeons, institutions, and the public. Because there may be wide differences in
      case mix, outcomes must be evaluated in light of the patient's preoperative
      status. All relevant preoperative conditions must be identified and weighted, so
      that when risk factor scores are combined in some fashion, they will provide a
      single preoperative risk estimate for the individual patient, representing the
      likelihood of dying as a consequence of the operation. Comparing the mean risk
      adjusted score of a group of patients undergoing the same procedure with the
      observed mortality rate for the same group yields an index of the quality of
      care, provided all preoperative risk scores are calculated with reference to the
      same benchmark. We question the logic and wisdom of surgical outcome analysis
      because of the infinitely complex nature of biological and pathological
      processes, as well as the practical problems of reliable data collection. The
      assumption of true scientific accuracy may be illusory. Even though risk adjusted
      outcome analysis has merit in studying trends in therapy, it should be regarded
      with caution when used as a tool for evaluating quality of care. If publicized at
      all, the results should not be represented as "hard" scientific fact.

PMID- 8574025
TI  - Pretreatment of human myocardium with adenosine during open heart surgery.
AB  - BACKGROUND: Depressed myocardial performance after cardiac surgery can be
      contributed to ischemic reperfusion injury (IRI) incurred during and following
      the cardiopulmonary bypass (CPB). Myocardial preconditioning (PC) achieved by
      brief ischemia and subsequent reperfusion appears to be a clinically useful
      method of improved cardiac protection during surgery involving CPB by retarding
      IRI. Based on animal studies, activation of cardiac adenosine (ADO) receptors
      prior to the prolonged ischemic period appears to mimic this PC phenomenon. AIMS
      AND METHODS: We investigated whether the human myocardial PC can be mimicked with
      ADO in the setting of the coronary artery bypass graft (CABG). The specific
      proposed objective of this study was to determine whether ADO infusion just prior
      to starting the CPB can improve post-CPB myocardial hemodynamics. Patients
      undergoing elective CABG with poor ventricular function (ejection fraction
      approximately 30%), and with at least three-vessel disease were selected for this
      study (n = 7 ADO, and n = 7 control). RESULTS: Our results show that ADO infusion
      (250-350 micrograms/kg X 10 min) just prior to CPB resulted in an immediately
      improved postbypass cardiac index (CI) in the OR (CI increase of 41.5% +/- 11.1%
      for ADO vs 9.7% +/- 6.0% for control, p < 0.05). Forty hours postoperatively in
      the intensive care unit, ADO patients had improved CI (3.3 +/- 0.2 L/min per m2
      for ADO, vs 2.6 +/- 4 L/min per m2 for control, p < 0.05). ADO patients
      maintained lowered resting heart rate (90 +/- 6 for ADO, vs 108 +/- 4 for
      control, p < 0.05) 40 hours after surgery. ADO patients also released
      significantly less CPK during the first 24 hours of the postoperative period.
      CONCLUSION: Based on these measurements, ADO pretreated patients had improved
      ventricular performance postoperatively. It also appears that ADO pretreatment
      results in lowered postoperative myocardial energy demand and less myocellular
      injury during CPB. To our knowledge, this is the first study to demonstrate that
      human myocardium can be hemodynamically improved with ADO pretreatment, and may
      be protected against IRI incurred during and following the CPB. We believe that a
      cardiac surgeon may now have the unique opportunity to confer myocardial
      protection during and after a cardiac surgical procedure.

PMID- 8574028
TI  - Utilization of triple-lumen balloon catheter for occlusion of the ascending aorta
      during distal aortic arch surgery with hypothermic retrograde cerebral
      circulation technique through left thoracotomy.
AB  - A technique of using a triple-lumen balloon catheter for occlusion of the
      ascending aorta in patients with distal aortic arch aneurysm during open proximal
      anastomosis utilizing hypothermic retrograde cerebral circulation technique
      through left thoracotomy was described. The balloon greatly facilitated (1)
      occlusion of the ascending aorta without cross clamping, (2) delivery of
      cardioplegic solution, (3) suctioning blood pooled in the aortic arch, and (4)
      prevention of entrance of debris into the left ventricle or coronary arteries.

PMID- 8574029
TI  - Muscle tamponade to control venous bleeding around grafts to deeply
      intramyocardial coronary arteries.
AB  - Considerable difficulty may be encountered in controlling persistent venous
      bleeding from the cut myocardial edges when coronary grafts have to be
      constructed to a deeply intramyocardial portion of the left anterior descending
      coronary artery. We describe a safe, inexpensive, and highly effective method of
      dealing with this problem using muscle tamponade with a prepared segment of
      rectus abdominis muscle. The technique has been used with uniform success and
      without complication in more than 60 patients.

PMID- 8574030
TI  - Selection of MR images for automated segmentation.
AB  - MR images show a large range of contrast for various tissues in the body and are
      ideal for multispectral segmentation. Typically, only two MR images (dual-echo
      series) are used for segmentation; however, other images are often available. We
      evaluated MR images from 40 patients to determine the optimal type and number of
      images required for segmentation of tissues associated with brain tumors (normal
      brain, edema, necrosis, and active tumor). Pattern recognition methods indicated
      that three MR images from the same slice location were adequate for segmentation,
      as defined by feature selection and feature extraction measures based on training
      fields. This result was also confirmed by visually examining segmented images for
      all 40 patients. This work demonstrates that by using existing image/statistical
      analysis techniques (feature selection and feature extraction), one can
      systematically determine the optimal type and number of MR images for tissue
      segmentation.

PMID- 8574031
TI  - Flow patterns in the dilated ischemic left ventricle studied by MR imaging with
      velocity vector mapping.
AB  - Magnetic resonance velocity vector mapping was used to study flow patterns in
      dilated and healthy left ventricles. Eleven patients (age mean +/- SD, 57 +/- 12
      years) with dilated left ventricle resulting from coronary artery disease and 10
      healthy volunteers (age 50 +/- 9) were studied. Cine gradient echo images were
      acquired in the left ventricle vertical and horizontal long axes. Vertical and
      horizontal velocity components in the horizontal long axis plane of the left
      ventricle were encoded simultaneously. Maps of velocity components were then
      processed into multiple computer generated streaks whose orientation and length
      corresponded to velocity vectors. The following parameters (mean +/- SD) differed
      significantly between the two groups: The heart rate (patients 70 +/- 11
      beat/min. controls 57 +/- 8, P < .001), end-diastolic volume (patients 264 +/- 83
      ml, controls 143 +/- 25 ml, P < .001), ejection fraction (patients 31% +/- 7,
      controls 61% +/- 5, P < .001), diameter of the inflow stream (patients 1.7 +/-
      0.6 cm, controls 3.2 +/- 0.3 cm, P < .001). In normal subjects the predominant
      direction of diastolic flow through the mitral valve was toward the apex, with
      short-lived vortices curling back behind each mitral leaflet. The vortex beneath
      the anterior leaflet tended to be larger and more dominant. In patients with
      dilated left ventricle, the inflow was directed toward the free wall, giving rise
      to a well developed circular flow pattern turning back toward the septum and
      outflow tract and persisting through diastole. Magnetic resonance velocity vector
      mapping is an excellent method for studying left ventricular flow
      patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574033
TI  - Acute occlusive ischemia of the rat intestine: early detection by MR imaging with
      polylysine-Gd-DTPA enhancement.
AB  - The purpose of this study was to assess the potential role of MR imaging with
      polylysine-Gd-DTPA enhancement in the early detection of acute occlusive
      intestinal ischemia in a rat model. After devascularization of the distal ileum
      in 12 rats, T2-weighted fast spin-echo MR images were acquired, followed by T1
      weighted images before and after IV administration of 0.1 mmol/kg polylysine-Gd
      DTPA. The signal intensity of the ischemic intestine did not differ significantly
      from that of the normal intestine before the administration of the contrast
      material. No mucosal or submucosal edema or hemorrhage was found in the ischemic
      intestine at histologic examination. After the administration of polylysine-Gd
      DTPA, the ischemic intestine lacked enhancement and its signal intensity was
      significantly lower than that of the normal intestine. MR imaging with polylysine
      Gd-DTPA enhancement can detect acute occlusive ischemia of the rat intestine at
      an early stage.

PMID- 8574032
TI  - Gadolinium zeolite as an oral contrast agent for magnetic resonance imaging.
AB  - The purpose of this study was to evaluate efficacy and safety of a gadolinium
      (Gd) zeolite suspension as an oral MRI contrast agent. Serial dilutions of GADO
      LITE Oral Suspension 1,2-300 micrograms of Gd(III)/mL) were prepared. MRI (T1 and
      T2 weighted) of standards and dogs (precontrast and postcontrast) were performed.
      Toxicity and Gd absorption were also assessed. Subsequently, 30 normal male adult
      volunteers were divided into six groups of five subjects each. Gd zeolite po
      suspension was administered before and after MRI in volumes and concentrations
      ranging from 250 to 1500 mL; 6 to 60 micrograms of Gd+3/mL. The images were rated
      (efficacy score) by a blinded reader. Vital signs, blood chemistries and
      urinalysis were recorded. Gadolite Oral Suspension produced excellent enhancement
      of the dog gastrointestinal (GI) tract. No toxicity or absorption of Gd was
      observed in dogs receiving doses up to 4 times the anticipated human dose daily
      for 14 consecutive days. In clinical trials, Gd zeolite significantly improved
      the efficacy scores for all groups and all pulsing sequences (all P values <
      .05). Efficacy scores and signal intensities generally increased with
      concentration and volume. No Gd was detected in blood or urine specimens. No
      significant adverse events were reported. Gd zeolite is a promising contrast
      medium for enhancement of the GI tract in MRI.

PMID- 8574034
TI  - First-pass contrast-enhanced inversion recovery and driven equilibrium fast GRE
      imaging studies: detection of acute myocardial ischemia.
AB  - The purpose of this study was (1) to monitor the dynamic effects of T1-enhancing
      and magnetic susceptibility contrast material on normal canine myocardium using
      inversion recovery (IR)- and driven equilibrium (DE)-prepared fast gradient
      recalled echo (GRE) sequences and (2) to determine the relative value of T1
      enhancing and magnetic susceptibility contrast material in detecting regions of
      ischemia in the same animal. Normal dogs (n = 5) and dogs with acute occlusion of
      the left anterior descending (LAD) coronary artery (n = 11) were studied using a
      1.5-T MR imager. ECG-gated fast IR-prepared GRE images were acquired using
      TI/TR/TE of 700/7.0/2.9 msec and a flip angle of 7 degrees. Fast DE-prepared GRE
      images were obtained using a flip angle of 12 degrees and a DE delay/TR/TE of
      60/10.2/4.2 msec. Sequential images were acquired to monitor transit of 0.05
      mmol/kg gadodiamide injection and 0.2 and 0.4 mmol/kg sprodiamide injection. On
      slice-nonselective IR fast GRE images, gadodiamide caused significant enhancement
      of the normal myocardium and the left ventricular (LV) chamber blood. In dogs
      with LAD occlusion, the ischemic region was defined as an area of low signal
      intensity (SI). On DE-prepared GRE sequences, administration of sprodiamide
      resulted in a substantial decrease in signal from normal myocardium and LV
      chamber blood in normal dogs. In animals subjected to LAD occlusion, this
      contrast medium produced a transient decrease in SI from normal myocardium (P <
      .05) and no significant change in SI from ischemic myocardium.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8574035
TI  - MR-guided biopsy of the breast after lumpectomy and radiation therapy using two
      methods of immobilization in the lateral decubitus position.
AB  - We describe two methods of breast immobilization using the lateral decubitus
      position to increase patient comfort and access to the axillary tail for MR
      guided biopsy in the postsurgical or irradiated breast. The first method uses a
      compression device with good immobilization but poor patient tolerance. The
      second approach uses a thermoplastic mesh material to form a rigid exoskeleton
      around the breast: immobilization is adequate and patient acceptability is good.
      The latter method is preferred and requires formal evaluation in larger scale
      trials.

PMID- 8574036
TI  - Temporal phase unwrapping for CINE velocity imaging.
AB  - A simple algorithm named temporal phase unwrapping (TPU) is introduced to address
      the phase aliasing problem in time-dependent phase contrast (CINE-PC) velocity
      imaging. The method exploits the temporal continuity of velocity field and
      unwraps the phase along time. TPU only involves a one-dimensional (1D) temporal
      integration; therefore, many complications in 2D or 3D spatial phase unwrapping
      are avoided. Differential velocity maps (DVM) between adjacent movie frames are
      first calculated from the complex MR images. The DVMs have no phase aliasing as
      the differential velocities are much smaller than the absolute velocities.
      Aliasing-free velocity maps are obtained by integrating the DVMs along the time
      direction provided an aliasing-free reference velocity map (RVM) is found as a
      starting point of the integration. Typically, such RVMs are always available
      within the cardiac cycle, especially in diastole where the blood flow is the
      lowest. In vivo results from fully automated processing and detailed discussion
      on noise behavior are presented.

PMID- 8574037
TI  - A monoclonal antibody to alpha 4-integrin reverses the MR-detectable signs of
      experimental allergic encephalomyelitis in the guinea pig.
AB  - Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune
      disease of the CNS characterized by blood-brain barrier breakdown, cerebral edema
      formation, lymphocyte infiltration, and demyelination, and is used as an animal
      model of multiple sclerosis (MS). MR imaging is important for the diagnosis of MS
      and for the evaluation of potential new therapies. In this study, T2-weighted and
      T1-weighted contrast-enhanced MR imaging was used to evaluate the effectiveness
      of an antiadhesion therapy in EAE. Leukocyte-endothelial adhesion at the blood
      brain barrier is considered an essential step in the mediation of CNS leukocyte
      infiltration in EAE. AN100226m, a monoclonal antibody to alpha 4 integrin has
      been previously shown to reverse the clinical and histologic signs of EAE by
      blocking this interaction. In the present study, AN100226m treatment in acute EAE
      significantly decreased contrast enhancement of the CNS parenchyma indicating
      closure of the blood-brain barrier. The percentage of pixels due to leakage of
      contrast material in T1-weighted images decreased to < 4% in AN100226m-treated
      animals whereas it was increased to 15% in control animals (P < .05, Mann-Whitney
      rank sum test). A decrease in CNS abnormalities associated with cerebral edema
      and inflammation was also observed on T2-weighted images (P < .05, Mann-Whitney
      rank sum test). Thus, an antibody to alpha 4 integrin reversed the blood-brain
      barrier permeability changes characteristic of acute EAE. In addition, the
      further accumulation of inflammatory edema was prevented and preexisting edema
      was resolved.

PMID- 8574038
TI  - MR imaging in graft-dependent recurrent hyperparathyroidism after
      parathyroidectomy and autotransplantation.
AB  - The purpose of this study was to compare the value of MR imaging versus
      sonography in the detection of hyperfunctioning transplanted parathyroid tissue.
      After parathyroidectomy and autotransplantation of parathyroid tissue to the
      forearm, 14 patients were examined with sonography and MR imaging. Five of these
      patients had recurrent hyperparathyroidism. In three of these five, sonography
      found one echolucent nodule. MR imaging in all three patients detected, in
      addition to this nodule, other small nodules of hyperplastic parathyroid tissue,
      which were confirmed intraoperatively. In the other two patients, sonographic and
      MR imaging findings were negative. Further investigations showed that both
      patients had a fifth parathyroid gland. In the patients without recurrent
      hyperparathyroidism, sonography showed scar tissue only, whereas MR imaging found
      some tiny, contrast-enhancing structures in two patients, probably autograft
      material. MR imaging seems to be more sensitive than sonography in detecting
      hyperfunctioning autotransplanted parathyroid tissue.

PMID- 8574039
TI  - Clinical utility of a new contrast option from magnetization transfer contrast.
AB  - Two magnetization transfer (MT) contrast effects, a T2-like effect and the
      improved contrast observed when gadolinium is used with MT, are combined in a
      single sequence. Forty patients (22 males:18 females; mean age, 45 years (23-87))
      with suspected intracranial pathology underwent MRI on a 1.5 Tesla system. Of 46
      lesions; seven were ischemic, five infective, seven neoplastic, four hemorrhagic,
      four multiple sclerosis, seven human immunodeficiency virus (HIV)
      leukoencephalopathy, nine normal/miscellaneous, and three gliosis. A conventional
      spin-echo sequence (TR 900 TE 15) was used with on-resonance binomial MT pulses.
      The sequence was performed postgadolinium +/- MT. The signal intensity ratios +/-
      MT were: white matter, 0.62 +/- 0.03; gray matter, 0.75 +/- 0.04; ischemia,
      edema, and demyelination, 0.75 (0.57-0.86); and gadolinium/methemoglobin, 0.85
      (0.81-0.98). Areas which exhibited MT had T2-like contrast and those that did not
      maintained expected contrast for the given parameters. The result was a
      combination of T2-like contrast, gadolinium enhancement, and dark cerebrospinal
      fluid (CSF) providing both increased sensitivity to lesions which exhibited both
      contrast features and improved delineation of periventricular lesions.
      Furthermore, the differential signal between T2-like contrast of edema and
      gadolinium enhancement in neoplastic or infective lesions was maintained.

PMID- 8574040
TI  - Inflammatory pseudotumor of the liver: appearance on contrast enhanced helical CT
      and dynamic MR images.
AB  - The dynamic pre- and post-contrast MRI and helical CT imaging findings in a
      patient with inflammatory pseudotumor of the liver are described. On immediate
      post gadolinium spoiled gradient echo images multiple, ill defined, irregular,
      and intensely enhancing lesions were seen. Rapid washout of contrast was noted.
      Periportal involvement was also shown on T2-weighted fat suppressed images.
      Lesions showed greater conspicuity on MRI than CT. MRI findings in this rare
      entity led to performance of a diagnostic open surgical biopsy.

PMID- 8574041
TI  - The quantitative relation between T1-weighted and T2-weighted MRI of normal gray
      matter and iron concentration.
AB  - A retrospective analysis of 158 T1-weighted and T2-weighted MRI scans of normal
      brains at 0.5 and 1.5 Tesla was performed. Signal intensities in the frontal
      cortex, caudate nucleus, putamen, and globus pallidus were divided by those of
      frontal white matter; and these gray/white ratios were correlated with iron
      concentration, estimated from the anatomical region and age of the patient.
      Intraregional plots were also made of gray/white ratio versus age for the 1.5
      Tesla scans. The changes in both T1-weighted and T2-weighted ratios were
      consistent with the hypothesis that 1/T1 and 1/T2 vary linearly with iron
      concentration, and the corresponding coefficients, determined separately from the
      interregional and intraregional plots, were generally in agreement. Furthermore,
      the variability of the MRI ratios at 1.5 Tesla was consistent with expected iron
      variability except for the cortex, in which partial volume errors due to sulci
      and white matter caused increased variations. The MRI results agreed well with in
      vitro data on T1 and T2 in tissue specimens and with other MRI studies. When
      compared with T1 and T2 in ferritin solution, a significant "tissue relaxation
      enhancement" was found, attributable to slower diffusion and clustering of
      ferritin in tissue.

PMID- 8574042
TI  - Phased-array magnetic resonance imaging of the carotid artery bifurcation:
      preliminary results in healthy volunteers and a patient with atherosclerotic
      disease.
AB  - A high resolution MR imaging technique using a custom designed flexible phased
      array surface coil was developed to examine the wall of the carotid artery
      bifurcation in vivo. The phased-array consisted of two overlapping coils which
      increased the image signal-to-noise ratio at the depth of the carotid artery by
      approximately 70%, relative to a similarly sized single loop coil. The imaging
      protocol included a 2D T1-weighted (T1W) spin-echo scan and cardiac gated T2
      weighted and proton density-weighted (PDW) fast spin-echo (FSE) scans. Images
      were obtained of six healthy volunteers and of one patient with known
      atherosclerotic disease several days before carotid endarterectomy. On T1W and
      PDW images of the healthy volunteers, the carotid arterial wall appeared to be
      comprised of two concentric rings; a high signal inner ring and a lower signal
      outer ring. The MR images of the patient revealed a calcified carotid bifurcation
      plaque which was confirmed during surgery. The endarterectomy specimen was imaged
      in vitro with MR and then sectioned histologically for correlation with the
      patients in vivo images. Our preliminary findings indicate that a high resolution
      technique may provide a noninvasive technique to study atherosclerosis of the
      carotid bifurcation.

PMID- 8574043
TI  - Superparamagnetic iron oxide hepatic MR imaging: efficacy and safety using
      conventional and fast spin-echo pulse sequences.
AB  - The purpose of this study was to evaluate the technical efficacy and safety of iv
      ferumoxides (Feridex), a superparamagnetic iron oxide contrast agent for
      detection of hepatic lesions using conventional spin-echo and fast spin-echo MR
      images. Precontrast and postcontrast MR studies were performed on 25 patients
      with suspected focal hepatic lesions. Conventional T1- and T2-weighted MR images,
      as well as fast spin-echo and fat suppressed fast spin-echo MR images, were
      evaluated. Quantitative assessment of the contrast agent was performed obtaining
      region of interest measurements of the liver, spleen, and selected hepatic
      lesions. The pulse sequences were also evaluated subjectively for overall image
      quality and a subjective assessment of lesion detection. The use of a
      superparamagnetic iron oxide contrast agent led to a decrease in hepatic signal
      intensity on all pulse sequences. Lesion-to-liver contrast increased 41.1%,
      36.5%, and 32.0% on the conventional T2, fast spin-echo, and fat suppressed fast
      spin echo pulse sequences, respectively. Lesion-to-liver contrast decreased on
      the T1-weighted postcontrast pulse sequence by 23.8%. Despite improvement in
      lesion-to-liver contrast, radiologists subjectively preferred the precontrast
      sequences because of overall better image quality. At a dose of 10 mumol/kg,
      ferumoxides favorably impacts lesion-to-liver contrast, and may be useful in
      hepatic imaging, more with conventional T2-weighted spin-echo pulse sequences
      than with T2-weighted fast spin-echo pulse sequence.

PMID- 8574044
TI  - Comparison of ultrasound, CT, and MR imaging in the evaluation of candidates for
      TIPS.
AB  - To compare ultrasound (US), CT, and MRI in the evaluation of hepatic vascular
      anatomy, portal and splenic venous flow, and collateral pathways (varices and
      spontaneous shunts) in candidates for transjugular intrahepatic portosystemic
      shunting (TIPS), 17 patients with history of refractory variceal bleeding or
      intractable ascites underwent duplex US, contrast-enhanced CT, and MRI before
      TIPS. The appearance of portal and hepatic anatomy was graded from 1 (not
      visible) to 4 (excellent visualization) independently by four radiologists.
      Presence and direction of portal and splenic venous flow, and presence and
      location of varices and spontaneous portosystemic shunts were also assessed.
      Results and effects of interobserver variation were assessed for significance
      using Friedman's ANOVA and Wilcoxon's signed-rank test. MRI yielded higher scores
      than CT or US for hepatic veins (P < .0001) and inferior vena cava (P < .0001).
      MRI and CT scored better than US for portal vein branches (P = .012) and splenic
      vein (P = .0038). All tests demonstrated the main portal vein well, with no
      statistically significant difference. US and MRI were more sensitive than CT for
      detecting portal vein flow and direction (US 76%, CT 0%, MRI 82%). MRI was most
      sensitive for splenic vein flow and direction (US 41%, CT 0%, MRI 76%). CT and
      MRI were more sensitive than US in detecting varices (US 5%, CT 50%, MRI 58%) and
      spontaneous shunts (US 13%, CT 75%, MRI 75%). Interobserver variation did not
      influence results significantly P = .3691). MRI provides the most useful
      information and may be the preferred single imaging test prior to TIPS.

PMID- 8574046
TI  - Dynamic evaluation of exercising leg muscle in healthy subjects with echo planar
      MR imaging: work rate and total work determine rate of T2 change.
AB  - Echo planar MR imaging of the leg was performed in nine healthy volunteers to
      better understand the dynamic relationship between exercise and changes in muscle
      T2. Imaging and T2 calculation was performed before, during, and after ankle
      dorsiflexion exercises using a TR of 9 seconds and a TE of 60 msec. Performing 9
      second duty cycles, six of the subjects exercised for sets of 12 duty cycles,
      three with a graded series of weights and pulleys and three with an isometric
      orthotic device graded in varying percentages of maximum voluntary contraction.
      The other three volunteers performed duty cycles to fatigue. Gastrocnemius and
      soleus muscle T2 relaxation times were unchanged before, during, and after
      exercise. The tibialis anterior muscle showed an initial brief 1.7-6.2% decrease
      in T2 values after starting exercise, followed by a linear increase. Maximum T2
      values and percent changes were higher for higher work rates (P < .05), and the
      rate of T2 change increased in a linear fashion with increasing work rates. By
      using rapid serial MR imaging, we show that the rate of muscle T2 change bears a
      simple linear relationship to muscle work. This technique may be exploited in
      both diagnostic and rehabilitation procedures.

PMID- 8574045
TI  - Appearance of the normal pericardium on coronary MR angiograms.
AB  - We evaluated the appearance of the normal pericardium on breath-hold MR images
      used to visualize coronary arteries. A coronary MR angiogram was obtained in 23
      subjects (17 healthy volunteers and six patients with no known pericardial
      disease) using a breath-hold K-space segmented gradient-recalled echo sequence
      with fat suppression. Each coronary MR angiographic study included imaging planes
      equivalent to the following echocardiographic planes: four-chamber view, vertical
      two-chamber view, and two short-axis views (at base and mid ventricular level).
      The average pericardial thickness was 1.7 mm (range, 1.5-2.0 mm), and an average
      length of 60 mm (range, 20-110 mm) of pericardium was visualized. A significantly
      longer portion of the pericardium was seen in the vertical two-chamber view and
      the basal short-axis view than in the two other views (P < .001). Normal anatomic
      variations and overlapping structures and image artifacts can alter the
      appearance of the pericardium. Breath-hold MR imaging techniques used for
      coronary MR angiography allow routine, time-efficient evaluation of large
      portions of the pericardium.

PMID- 8574047
TI  - Unsupervised measurement of brain tumor volume on MR images.
AB  - We examined unsupervised methods of segmentation of MR images of the brain for
      measuring tumor volume in response to treatment. Two clustering methods were
      used: fuzzy c-means and a nonfuzzy clustering algorithm. Results were compared
      with volume segmentations by two supervised methods, k-nearest neighbors and
      region growing, and all results were compared with manual labelings. Results of
      individual segmentations are presented as well as comparisons on the application
      of the different methods with 10 data sets of patients with brain tumors.
      Unsupervised segmentation is preferred for measuring tumor volumes in response to
      treatment, as it eliminates operator dependency and may be adequate for
      delineation of the target volume in radiation therapy. Some obstacles need to be
      overcome, in particular regarding the detection of anatomically relevant tissue
      classes. This study shows that these improvements are possible.

PMID- 8574048
TI  - Imaging of ovarian cancer.
AB  - Cross sectional imaging continues to play an increasingly important role in
      ovarian cancer diagnosis, staging, and treatment follow-up. Screening for ovarian
      cancer remains a controversial subject. The combined use of clinical examination,
      CA-125, and endovaginal ultrasound (US) are being advocated for high risk
      patients but consensus recommendation for screening awaits further studies. In
      characterization of an ovarian neoplasm US is indisputedly the primary imaging
      approach. Only when US is inconclusive are further studies warranted. Magnetic
      resonance imaging (MRI) is generally preferred to computer tomography (CT). A
      prospective MRI-CT clinical trial has not been performed as yet. Preoperative
      staging by imaging is slowly gaining its acceptance. This is mostly due to the
      awareness of the difficulties and inaccuracy in surgical staging when unsuspected
      extensive disease is present. Furthermore, in known resectable ovarian cancer,
      primary chemotherapeutic cytoreduction may be a better treatment option. Accuracy
      of CT and MRI in staging ovarian cancer is similar, CT, however, is faster, more
      widely available, and less expensive; these are important attributes that are
      decisive in this time of health reimbursement constraints.

PMID- 8574049
TI  - Ex vivo evaluation of ferromagnetism, heating, and artifacts of breast tissue
      expanders exposed to a 1.5-T MR system.
AB  - Three breast tissue expanders were evaluated for compatibility with MR imaging
      (1.5 Tesla). The metallic components of the breast tissue expanders were shown to
      be nonferromagnetic, heating < or = .2 degrees C and the artifacts varied. These
      results indicate that MR procedures may be performed safely in patients with
      these implants; however, artifacts may obscure implant leaks or breast lesions if
      located near and metal portion of the breast tissue expanders.

PMID- 8574050
TI  - Feasibility of MR diffusion studies in the kidney.
AB  - Renal apparent diffusion coefficients (ADCs) were anisotropic within and
      significantly different between cortex and medulla using a relatively motion
      insensitive one-dimensional technique in 20 volunteers. ADC values ranged from
      1.79 +/- .39 to 2.95 +/- .58 (x 10(-3)mm2/sec), relatively high but similar to
      other reports. Further investigation may help clarify this data, and determine
      whether the findings result from diffusion properties (and/or radially oriented
      parenchymal architecture), or artifacts due to factors such as bulk motion.

PMID- 8574051
TI  - An index to predict outcome of surgery for reflux esophagitis based on the AFP
      classification.
AB  - Fifteen patients with reflux esophagitis were treated surgically from July 1990
      to April 1994. We evaluated these patients using the anatomic-functional
      pathologic (AFP) classification both prior to and following the operation. An
      objective index for surgical outcome was devised. By using the grades Ai, Fj, and
      Pk, the i2 + j2 + k2 score was determined. The scores ranged from 3 to 22 (mean
      9.1 +/- 5.4) prior to the operation. Postoperatively, 12 (80%) of 15 patients
      showed a complete recovery with a numerical score of 0, and their symptoms also
      disappeared. The scores of these 12 patients prior to the operation ranged
      between 3 and 11. However, the other 3 patients did not exhibit a complete
      recovery. Their scores prior to the operation ranged between 17 and 22, and the
      symptoms in 2 of these 3 patients persisted following the operation. These
      results suggest that surgical treatment for reflux esophagitis can be expected to
      be successful if the preoperative AFP score is less than 11.

PMID- 8574052
TI  - Quantitative assessment of anal canal sensation in patients undergoing low
      anterior resection for rectal cancer.
AB  - To determine the influence of anal canal sensation on anal function after low
      anterior resection (LAR) for rectal cancer, anal canal sensation was
      quantitatively evaluated before and after LAR by measuring anal mucosal
      electrosensitivity (AMES), and the relationship between AMES and postoperative
      and function was explored. Sensory thresholds 1, 2, and 3 cm from the anal margin
      were recorded in 21 patients who underwent LAR for rectal cancer (LAR-I) before,
      then 1 and 4 months after their operation. Another 14 patients who had been
      followed up for more than 1 year (LAR-II) after LAR and 21 control subjects were
      also studied. The median preoperative sensory thresholds in the LAR-I group were
      higher than those in the controls, though the differences were not significant.
      The sensory thresholds in the LAR-I group 4 months after LAR were lower than
      those preoperatively, but they did not significantly differ from those in the LAR
      II and control groups. Although the postoperative sensory thresholds did not
      correlate with postoperative anal function, the preoperative sensory thresholds
      were higher in patients who were experiencing episodes of fecal incontinence 4
      months after their operation. These results suggests that the preoperative
      measurement of AMES is useful for identifying patients who are likely to have a
      poor quality of continence after LAR.

PMID- 8574053
TI  - Analysis of the factors influencing the quality of life of patients with advanced
      or recurrent breast cancer.
AB  - To investigate the factors influencing the quality of life (QOL) of Japanese
      patients with advanced or recurrent breast cancer, a newly developed QOL
      questionnaire, "The QOL Questionnaire for Cancer Patients Treated with Anticancer
      Drugs" (QOL-ACD), was answered by 23 patients, and a multiple regression analysis
      was performed. The demographic and medical factors relating to the overall QOL
      score and to the four categories of the QOL-ACD, namely (1) activity, (2)
      physical condition, (3) psychological condition, and (4) social relationships,
      were analyzed. The results indicated that skin metastasis, a heavier body weight,
      and bone metastasis had a strong negative influence on the overall QOL scroe,
      whereas endocrine therapy, the existence of a primary lesion, and more extensive
      first surgery had a strong positive influence on it. With regard to the analysis
      of the four categories, endocrine therapy was found to be positively related to
      all four categories. The multiple correlation coefficient (R) between the
      estimated overall QOL score and the observed overall QOL score was about 0.77.
      The results of this analysis showed that endocrine therapy can improve the QOL of
      patients with advanced or recurrent breast cancer, and that the QOL-ACD
      questionnaire could prove extremely useful for predicting the QOL of individual
      patients and for aiding clinicians in deciding on the most appropriate type of
      therapy for each patient.

PMID- 8574054
TI  - Percutaneous left ventricular assist system using a modification of the Dennis
      method: initial clinical evaluation and results.
AB  - A percutaneous left ventricular assist system (PLVAS) using a modification of the
      Dennis method was developed and implemented in 8 patients. Transseptal
      cannulation was performed under biplane fluoroscopy and/or transesophageal
      echocardiogram without encountering any problems. All the patients were in a
      state of severe cardiogenic shock, caused by acute myocardial infarction in 5,
      cardiomyopathy in 2, and postcardiotomy in 1, and were on intraaortic balloon
      pump support and/or percutaneous cardiopulmonary support (PCPS), in the form of
      partial cardiopulmonary bypass. Three patients who developed concomitant right
      heart failure required additional PCPS. All the patients were supported at 3.0 to
      4.0 l/min for 76-284h for an average time of 159h. Three patients were
      successfully weaned from PLVAS and one of these patients, who had suffered an
      acute myocardial infarction, was discharged from hospital. The complications
      directly related to this system were minimal. Our observations led to the
      conclusion that PLVAS using our modification of the Dennis method is a simple,
      easy, and safe means of maintaining adequate systemic circulation in severely ill
      patients. As PLVAS is particularly effective for patients in cardiogenic shock
      following acute myocardial infarction, we believe that it will be applied
      routinely by many cardiac surgeons and cardiologists in the future.

PMID- 8574056
TI  - The influence of surgical insults on restenosis after transluminal balloon
      angioplasty.
AB  - The influences of atherogenic response on restenosis after transluminal balloon
      angioplasty and the anastomosis of arterial reconstruction were investigated.
      Iliac transluminal balloon angioplasty was performed on 81 consecutive patients
      at 86 sites, between January, 1987 and December, 1992. A balloon angioplasty
      alone was performed in 58 patients at 60 sites, while distal revascularization
      was performed in 23 patients on 26 limbs, in association with the angioplasty. An
      improvement in the inflow of the distal grafts was achieved in 22 of these 23
      patients in 26 limbs. The combined distal revascularization included 21
      femoropopliteal bypasses, 3 femorofemoral bypasses, and 2 thromboendarterectomies
      at the profunda femoris arteries. A reduction in the luminal diameter after the
      balloon angioplasty was determined by means of follow-up arteriograms which
      showed no obvious progression of the restenosis at the angioplasty sites even
      when neointimal hyperplasia had developed at the anastomosis of the arterial
      reconstruction. The accumulative graft patency rate of the combined distal
      revascularization did not differ significantly from that of femoropopliteal
      reconstructions alone during the same study period. This study demonstrated that
      concomitant surgical insults do not have a detrimental effect on restenoses at
      angioplasty sites.

PMID- 8574055
TI  - Benefits of arterial reconstruction in claudication.
AB  - We conducted a midterm follow-up of 150 claudicants who underwent surgical
      reconstruction by assessing cumulative patency, survival, and palliation (graft
      patency in live patients) rates. Eighty-nine claudicants (group I) underwent
      direct (in situ) proximal revascularization, 33 (group II) had indirect (ex situ)
      proximal revascularization, while 28 (group III) had distal revascularization.
      The secondary patency rates at 3 years were 97.5% in group I, 97.0% in group II,
      and 75.0% in group III, respectively. Only one patient with limb graft thrombosis
      required below-knee amputation. There were 3 perioperative deaths (2 in group I
      and 1 in group II). The survival rates at 3 years were 86.0% in group I, 69.5% in
      group II, and 95.8% in group III, respectively. The palliation rates at 3 years
      were 84.8% in group I, 70.0% in group II, and 77.9% in group III, respectively.
      These findings indicate the midterm benefits of supra- and infrainguinal arterial
      reconstructions, and also suggest that the preoperative assessment of risks in
      individual patients, the selection of the appropriate operative procedure and
      graft material, and intensive postoperative follow-up and management of any
      associated disease are all important aspects in the treatment of claudicants.

PMID- 8574057
TI  - Biodegradation of glutaraldehyde-tanned human umbilical vein grafts.
AB  - A retrospective analysis of the long-term behavior of 111 glutaraldehyde-tanned
      human umbilical vein (HUV) grafts implanted between September 1977 and December
      1993 was conducted. A total of 81 patients, with a mean age of 68.7 years,
      received the grafts and were followed up for between 1 and 131 months. The 5-year
      primary cumulative patency rate for above-knee femoropopliteal bypass was 83.1%,
      whereas that of other bypasses was 60.9%. An aneurysm of the graft was defined as
      a physically apparent localized dilatation, with diffuse ectasia being excluded.
      There were 11 aneurysms found in 9 grafts, 2 of which arose at the factory-made
      suture lines. The accumulated incidence of aneurysms had reached 21.9% by the 6th
      year. One aneurysm compressed the graft and resulted in limb-threatening ischemia
      and another resulted in frank rupture. Moreover, reinforcement of the mesh could
      not prevent aneurysm development, the repair of which is mandatory due to the
      risk of rupture and acute thrombosis. The HUV grafts showed an acceptable patency
      rate in the above-knee location, but the incidence of aneurysm formation after 5
      years was abnormally high. Thus, both the risks and benefits of HUV grafts must
      be taken into account when considering their clinical application.

PMID- 8574058
TI  - The role of glucagon in the gastric hyperdynamic circulation of cirrhotic portal
      hypertensive rats.
AB  - The role of glucagon as a mediator of gastric hyperdynamic circulation, induced
      by carbon tetrachloride (CCl4), was assessed in cirrhotic rats. A selective
      elimination of pancreatic glucagon from the circulation was achieved by the
      intravenous infusion of a glucagon antiserum. Gastric blood flow was measured by
      laser-Doppler flowmetry. The glucagon antiserum had no effect on the blood flow
      in the stomach in control rats, while in cirrhotic portal hypertensive rats, the
      glucagon antiserum significantly reduced gastric blood flow (30%). The glucagon
      antiserum did not completely exclude the gastric hyperdynamic state in the
      cirrhotic rats. It would thus appear that glucagon contributes to a portion of
      the gastric hyperdynamic circulation associated with cirrhotic portal
      hypertension.

PMID- 8574059
TI  - An analysis of the possible factors contributing to the delayed return of gastric
      emptying after gastrojejunostomy.
AB  - The possible factors contributing to delayed-return gastric emptying (DRGE) after
      gastrojejunostomy were analyzed through a review of 955 consecutive patients who
      had undergone gastric surgery for the first time, which revealed 23 patients who
      had experienced DRGE. Of 7 consecutive patients who had undergone a reoperation
      for postsurgical gastroparesis syndrome, 3 were found to have experienced
      persistent DRGE. The chi-squared and/or Student's t-tests showed the significant
      factors to be (a) an age over 60, and (b) a history or nonresection gastric
      bypass, Roux-en-Y reconstruction, or reoperation for the preexistence of
      postoperative gastroparesis, with P values of less than 0.05. There was a higher
      incidence of DRGE in patients who had received a vagotomy, and there were
      increasing nutritional indices when patients were recovered from DRGE; however,
      vagotomy and malnutrition could not be considered independent variables. In
      conclusion, the incidence of DRGE was significant in patients aged over 60 who
      had undergone gastrojejunostomy, with nongastric resection, Roux-en-Y
      reconstruction, or reoperation for gastroparesis. In the event of DRGE, a longer
      period of supportive treatment is required to avoid unnecessary second surgery as
      most patients recover spontaneously, whereas a high incidence of persistent DRGE
      may occur following early reoperation.

PMID- 8574060
TI  - Formation of a fatal arterioportal fistula following needle liver biopsy in a
      child with a living-related liver transplant: report of a case.
AB  - A 2 1/2-year-old girl underwent a living-related liver transplantation for
      biliary atresia, following which four percutaneous liver biopsies were performed
      uneventfully during her hospital stay for the evaluation of recurrent rejection.
      Her condition improved without any complications, and she was discharged from
      hospital in a stable condition on postoperative day (POD) 51. However, 3 months
      later she was readmitted with marked ascites and a moderate elevation of her
      liver function tests. A color Doppler ultrasound (US) confirmed hepatofugal
      portal blood flow, and selective celiac arteriography demonstrated an
      intrahepatic arterioportal (A-P) fistula. An attempt to embolize the fistula
      failed and a surgical approach was attempted without success. The patient died
      from irreversible liver failure on POD 152. A review of the previous histologic
      analyses revealed that arterial components were present in the fourth biopsy
      specimen; for this reason it was hypothesized that this procedure may have led to
      the development of the A-P fistula.

PMID- 8574061
TI  - Sudden hemorrhage of the breast caused by breast cancer without skin invasion:
      report of a case.
AB  - A rare case of sudden hemorrhage caused by breast cancer is herein presented. A
      65-year-old woman was admitted to our hospital because of bleeding from her left
      breast. On physical examination, a continuous hemorrhage accompanied by an open
      cavity formation was observed in her left breast. She had no history of breast
      trauma. Her bleeding profile studies and liver function were both normal. In
      addition, no anticoagulation medication had been administered. The histological
      findings of the cavity wall indicated invasive ductal carcinoma without skin
      invasion. After carrying out chemotherapy, a standard radical mastectomy was
      performed.

PMID- 8574062
TI  - Colonic actinomycosis: report of a case and review of the literature.
AB  - Abdominal actinomycosis is a rare entity which presents some difficulty in
      establishing a correct preoperative diagnosis. We report herein the case of a 41
      year-old woman who developed abdominal actinomycosis involving the left colon and
      the surrounding retroperitoneum. The patient, who had an intrauterine
      contraceptive device (IUCD) in situ, presented with left flank pain and the signs
      and symptoms of an intraabdominal mass, which was initially diagnosed as a
      neoplasm originating from the left colon or the retroperitoneal space. Thus, a
      left colectomy was performed, but the histopathological pathological diagnosis
      revealed abdominal actinomycosis. We evaluated the diagnosis and treatment of
      this disease in light of the knowledge acquired from the available literature on
      this rare entity.

PMID- 8574063
TI  - Increases in pulmonary artery pressure and cardiac output due to the inhibition
      of nitric oxide synthesis during operative stress.
AB  - Pulmonary artery pressure (PAP), cardiac output (CO), and urinary nitrate, a
      stable endproduct of nitric oxide (NO), were measured pre- and postoperatively in
      eight patients who underwent esophagectomy for squamous cell carcinoma of the
      thoracic esophagus. A significant elevation of PAP and CO on the day of operation
      (POD 0) was accompanied by a low concentration of urinary nitrate. A reduction in
      PAP and CO, and an increase in nitrate to the preoperative levels, were found on
      PODs 2 and 3, respectively, but urinary nitrate decreased again after POD 3.
      Consequently, the changes in PAP and CO were closely correlated with the nitrate
      concentration. These results suggest that operative stress inhibited NO synthesis
      with a transitory induction of endogenous NO synthesis postoperatively.

PMID- 8574064
TI  - Laparoscopic repair of an abdominal hernia using an expanded
      polytetrafluoroethylene patch secured by a four-corner tacking technique.
AB  - An improved technique for performing laparoscopic repair of an abdominal hernia
      is described herein. To ensure a successful repair, it is most important that
      adequate tension of the expanded-polytetrafluoroethylene (e-PTFE) patch be
      achieved, and that the defect be completely covered and securely stapled. Our
      technique involves tacking the four corners of the patch to the abdominal wall
      with a 2-0 nylon suture using a straight needle, then stapling it to the anterior
      abdominal wall over the defect with a laparoscopic stapler. We believe that this
      technique is a safe and reliable method which will prove useful for laparoscopic
      surgery.

PMID- 8574065
TI  - Is median thoracic artery a target organ artery for estradiol and progesterone? A
      comparison with uterine artery.
AB  - PURPOSE: The aim of this study was to show the parallel evolution of the
      pulsatility index of the uterine artery and the one of the median thoracic
      artery. STUDY DESIGN: The study involved seven volunteer women, below 38,
      suffering from premature ovarian failure, who received E2 and progesterone
      replacement therapy. Plasma levels of E2, progesterone, follicle stimulating
      hormone and luteinizing hormone were measured and PI were studied and compared
      before treatment and on Days 13, 27 and 41. RESULTS: Before treatment, a high
      resistance vascular for both arteries is uniformly found. The curves show with
      the increasing of the E2 plasma levels, a decrease in the PI of UA and MTA with a
      fall at Day 13. We compared the mean values in MTA and UA PI. No statistical
      difference between the three mean values in PI obtained at Day -1, Day 13 and Day
      41 was demonstrated. CONCLUSION: The results suggest that median thoracic artery
      is a target organ artery. Such as the UA, the MTA vascular resistance is
      according to the variations of plasma levels of E2. In consideration of it
      rectilinear and superficial type, this led us to study this artery when we use
      different sorts of replacement therapy, and particularly in the oocyte donation
      program.

PMID- 8574066
TI  - The influence of supraphysiologic estradiol levels on human nidation.
AB  - OBJECTIVE: Exogenous estradiol (E2) has a well-recognized interceptive action
      when administered shortly after ovulation. The influence of extremely elevated
      levels of endogenous E2 on human oocyte fertilization and implantation are
      unclear. The purpose of this study was to evaluate a potential antinidatory role
      of extremely high endogenous E2 concentrations on implantation and pregnancy
      during in vitro fertilization-embryo transfer (IVF-ET). METHODS: Twenty-five
      patients receiving human menopausal gonadotropins (hMG) following midluteal GnRHa
      administration for IVF-ET, in which the maximal E2 concentration was > 5000 pg/ml
      (range 5358-16,344 pg/ml) were studied. Cycle parameters including oocyte and
      embryo characteristics, fertilization, cleavage, and implantation rates as well
      as pregnancy outcomes were compared to those of 25 patients treated
      contemporaneously whose treatment cycles had peak E2 values < 3500 pg/ml.
      Patients groups were matched for age, infertility diagnoses, duration of
      infertility and stimulation protocol. RESULTS: Cycles characterized by very high
      endogenous E2 levels resulted in significantly more oocytes per retrieval (21.4
      +/- 1.7 versus 8.4 +/- 0.6; P < 0.0001), fewer postmature oocytes (1.6% +/- 1.0%
      versus 14% +/- 5.0%; P < 0.03), and a decreased fertilization rate (63% +/- 4.0%
      versus 73% +/- 3.0%; P < 0.04) compared to control cycles. There were no
      differences in the overall mean morphologic grade or cleavage rates between
      groups. However, high E2 cycles were associated with a significantly increased
      implantation rate (14% +/- 4.0% versus 8.0% +/- 4.0%; P < 0.01) and pregnancy
      rate per embryo transfer (62% +/- 16% versus 36% +/- 16%; P < 0.01) compared to
      controls. The incidence of spontaneous abortion did not differ between groups.
      CONCLUSIONS; Extremely high endogenous E2 levels do not appear to adversely
      affect implantation or overall cycle pregnancy rates in IVF-ET cycles. However,
      impaired fertilization rates in such cycles support a potential adverse effect on
      oocyte quality.

PMID- 8574067
TI  - Color-Doppler velocimetry of uterine arteries in pregnant and nonpregnant
      patients during multiovulation induction for IVF.
AB  - OBJECTIVES: To evaluate uterine artery resistance during multiovulation induction
      in relation to the implantation rate in patients attending in vitro fertilization
      (IVF) cycles. PATIENTS: Multiovulation induction for IVF was monitored by daily
      determination of the pulsatility index (PI) of the uterine arteries, obtained by
      a transvaginal probe (6.5 MHz) implemented with color-flow imaging. Doppler data
      were obtained from 5 days before hCG administration to the day of follicular
      aspiration. One IVF cycle was monitored in 70 patients. In 17 patients, 41 IVF
      cycles were monitored until a successful attempt occurred. RESULTS: In the 70
      patients studied during one IVF attempt, the PI of the uterine arteries
      significantly varied (P < 0.001) in the different phases of the cycle. In the 24
      patients who conceived, a significantly lower PI (P < 0.03) was found throughout
      the cycle. This result was mainly due to a highly significant difference of PI
      values observed the day after hCG administration (P < 0.005). In the 17 patients
      who conceived after 1 to 4 negative in vitro fertilizations, no significant
      difference in PI was observed in the uterine artery resistance in cycles in which
      implantation was or was not successful. CONCLUSIONS: Uterine artery resistance
      varies significantly during phases of the induction therapy. Uterine artery
      resistance is lower throughout the course of multiovulation induction in patients
      with higher pregnancy rates. The PI on the day after hCG administration was the
      best index of pregnancy rate. Low uterine artery resistance was present even in
      negative attempts in patients who eventually achieved a successful implantation.
      PI values < or = 3 can be considered a favorable prognostic factor for future IVF
      cycles.

PMID- 8574068
TI  - In vitro fertilization: a cost-effective alternative for infertile couples?
AB  - OBJECTIVE: To evaluate the cost of in vitro fertilization by calculating the cost
      of a live birth using this technology and determine cost variation according to
      the clinical characteristics of a particular population. DESIGN: Retrospective
      review of infertile couples who presented for their first IVF cycle in 1993. A
      fraction of the total population was assigned to three groups A, B, and C with
      high, intermediate and low probability of pregnancy respectively and their
      reproductive performance was evaluated until September 1994 or a maximum of three
      IVF cycles have been completed. SETTING: The in vitro fertilization program at
      the Brigham and Women's Hospital, Boston. PATIENTS: 182 couples who presented for
      their first IVF cycle in 1993. MAIN OUTCOME MEASURE: The cost of a successful
      pregnancy using IVF in the three groups and in the general population was
      calculated by dividing the average cost of an IVF cycle by the fraction of the
      cycles resulting in a successful pregnancy. RESULTS: The cost of a successful
      pregnancy in group A, B and C ranged from $22,857 to $42,666 after 1 cycle and
      from $26,800 to $74,666 after 3 IVF cycles. The average cost for the 182 patients
      was $29,120 after 1 cycle and $31,590 after a maximum of 3 IVF cycles.
      CONCLUSION: The cost of a successful pregnancy: (1) was comparable to other
      options available to an infertile couple such as adoption and tubal surgery, (2)
      was 50% to 70% cheaper in the group with a highest probability of pregnancy when
      compared to the group with the lowest probability of pregnancy, and (3) did not
      vary significantly after 1 or 3 IVF cycles in most groups.

PMID- 8574070
TI  - Mini-swim-up: a new technique of sperm preparation for intracytoplasmic sperm
      injection.
AB  - PURPOSE: The male factor is nowadays one of the major problems in the treatment
      of infertility. New methods of assisted fertilization such as the
      intracytoplasmic sperm injection (ICSI) show better fertilization and pregnancy
      rates than classical IVF. METHOD: In this study, we present a new technique of
      sperm preparation: the "mini-swim-up." CONCLUSION: This technique, used in
      conjunction with the ICSI procedure, improves pregnancy and fertility rates in
      cases of severe oligoasthenoteratozoospermia.

PMID- 8574069
TI  - Fluorescent in situ hybridization analysis of chromosomally normal gametes and
      abnormal arrested embryos.
AB  - OBJECTIVE: The purpose of the present study was to investigate if the arrested
      embryos from a couple with several previously failed IVF treatments were
      chromosomally normal. Probes for chromosomes X, Y and 18 were used. RESULTS: A
      couple had undergone 7 in vitro fertilization treatments over a 2 1/2-year period
      without achieving a pregnancy. In each cycle, where fertilization was obtained,
      the development of the embryos was arrested. Fluorescent in situ hybridization
      probes for chromosomes X and Y (and 18) was carried out on gametes and on embryos
      in 2 separate cycles. Sperm and oocytes were normally haploid X0 or Y0. The
      nuclei of the blastomeres were fragmented and mosaic for X or Y, or monosomic X0,
      despite the fact that 2 pronuclei had been assessed on day 1 following
      intracytoplasmic sperm injection. CONCLUSION: Chromosomally normal gametes can
      result in abnormal embryos manifested by arrested development and unexplained
      infertility.

PMID- 8574071
TI  - Evaluating the accuracy of different sperm counting chambers by performing strict
      counts of photographed beads.
AB  - PURPOSE: To suggest a method for evaluating the accuracy of different kinds of
      sperm counting chambers by eliminating errors concerned with human skills or
      semen properties. In this method, various concentrations were prepared from
      stocks of commercially available latex beads (Accu-beads, Hamilton-Thorn
      Research, Beverly, MA). Samples from identical preparations were loaded into
      different types of chambers, namely, hemocytometer (Neubauer, improved double,
      Superior Ltd, Germany), Makler (Sefi Medical Instruments, Haifa, Israel) and
      Horwell (Horwell Ltd, London, UK). Beads were counted by both direct microscopic
      observations and by strict scanning of their photographed images. RESULTS: In all
      cases, counts by direct observation were about 5% higher than strict counts of
      the same photographed beads. Counting photographed beads showed high
      reproducibility (average CV of 5.1%) between samples in the two wells of the
      hemocytometer. Counts of photographed beads, sampled from identical stocks, were
      on average slightly lower in the Makler chamber (20.7 x 10(6)/ml) and much higher
      in the Horwell chamber (47.4 x 10(6)/ml) than counts in the hemocytometer (21.5 x
      10(6)/ml). Samples from three different batches of Accubeads revealed slight
      variation in counts between the batches and an average concentration of 11% above
      the number indicated on the commercial product. CONCLUSIONS; A technique that
      combined loading latex beads from identical stock into various chambers, proper
      covering of the tested samples and strict counting of photographed beads provided
      precise and reproducible results. By eliminating most errors related to human
      skills and semen properties, this method is suitable for evaluating the accuracy
      of counting chambers.

PMID- 8574072
TI  - Inhibition of bacterial growth in vitro by human ejaculate seminal plasma
      fraction 1 and its possible practical use in male infertility phenomenon.
AB  - PURPOSE: The in vitro bacteriostatic effect on bacteria by a fraction of human
      ejaculate (HuSePl-Fr1) was studied. METHOD: As bacterial indicators, Pseudomonas
      aeruginosa (Pa), total coliforms (Tc), fecal coliforms (Fc), Escherichia coli
      (Ec), and Staphylococcus aureus (Sa) were used. These bacterial strains are known
      as agents that cause urinary and sexually transmitted infections (STI). RESULTS:
      Preliminary results suggest that HuSePl-Fr1 has a significant in vitro
      bacteriostatic effect on Pa and Sa at 42 degrees C. In addition, Pa was inhibited
      at 37 degrees C after 48 hr incubation. The remaining bacterial indicators were
      not affected. CONCLUSION: The results indicate a possible protective role of
      HuSePl-Fr1 in treatment of infertile men due to genital infections.

PMID- 8574074
TI  - Immobilized and hypo-osmotic swollen spermatozoa on intracytoplasmic sperm
      injection.

PMID- 8574073
TI  - Effect of the dam strain on the spontaneous incidence of cleft lip and palate and
      intrauterine growth of CL/Fr mouse fetuses.
AB  - PURPOSE: The effects of dam strain on the spontaneous incidence of the cleft lip
      and palate (CLP) and the intrauterine growth of transferred CLP-susceptible CL/Fr
      embryos were examined with an embryo transfer technique. The CL/Fr strain of
      embryos at the early blastocyst stage was transferred to the same dam strain and
      also to the CLP-resistant C57BL dam strain. A laparotomy was done on the 18th
      gestational day at which time the number of fetuses, the resorption sites and the
      fetus weight were recorded. Each fetus was checked for the presence of CLP. Five
      criteria to assess the reproduction and fertility as well as the fetus weight
      were then compared between both dam strains. RESULTS: The dam pregnancy rate and
      the fetus survival rate in the CL/Fr dam strain were both significantly lower
      than those in the C57BL dam strain. The resorption rate in the CL/Fr dam strain
      was significantly higher than that in the C57BL dam strain. The spontaneous
      incidence rate of CLP in the CL/Fr dam strain was also significantly higher than
      that in the C57BL dam strain. The fetus weight of the CL/Fr fetuses developed in
      the CL/Fr dam strain was significantly lighter than that of the CL/Fr fetuses
      developed in the C57BL dam strain. CONCLUSION: The results indicated that the CLP
      susceptible CL/Fr dam strain provided a less favorable uterine environment for
      the implantation, survival and intrauterine growth of the transferred CL/Fr
      embryos and also caused a higher spontaneous incidence rate of CLP. Thus, it can
      be concluded that the effect of the dam strain appears to play an important role
      on the spontaneous incidence of CLP and the intrauterine growth of the CL/Fr
      strain embryos transferred to both CL/Fr and C57BL dam strains.

PMID- 8574075
TI  - In vitro fertilization failure associated with sperm contamination by
      Trichosporon beigelii.

PMID- 8574076
TI  - Comparison of endocrinological and clinical profiles and outcome of IVF cycles in
      patients with one ovary and two ovaries.

PMID- 8574077
TI  - Two-step diagnosis of bilateral ectopic pregnancy after in vitro fertilization.

PMID- 8574078
TI  - Laser ablation of the mouse zona pellucida for blastomere biopsy.

PMID- 8574079
TI  - Loving care in the ambulance service.
AB  - The ambulance service should offer good care signified by humane and individual
      treatment of the patients, based on love to our fellow man. The aim of this study
      was to find out how loving care was practised in one ambulance service. The
      method for the study was the critical incident technique. Twelve paramedics, the
      majority of whom are qualified nurses, took part in the study; they were asked to
      describe, in writing, critical incidents in which they had acted with loving
      care. The paramedics' writings disclosed their ability to do their job with
      loving care, bearing on their cognizance, solicitude and empathy. On the whole,
      subject cognizance, the ability to judge and treat based upon the monitored
      symptoms of the patients, was apparent. In the main, subject solicitude loving
      care was shown through humbleness, consideration, closeness and being in rapport,
      and generally subject empathy, the paramedic's empathic capacity and his
      knowledge about man's behaviour in a crisis, became evident. From a clinical
      standpoint the study shows the importance of the paramedics possessing
      professional skill. As a contribution to science the study adds to continued
      research based upon descriptions made by other groups of personnel about the
      phenomenon to be studied; namely, loving care.

PMID- 8574080
TI  - Informed refusal and patient autonomy: using reflection to examine how nursing
      knowledge and theory affect attitudes.
AB  - Reflection is a medium increasingly being used in nursing to explore critical
      incidents, promote learning and integrate theory and practice. In this paper
      reflection is used to explore the influences of different types of nursing
      knowledge and theory upon reactions to informed refusal of treatment and the
      concept of patient autonomy. The paper contains consideration of the care of a
      Jehovah's Witness and her family who refused a badly-needed blood transfusion.

PMID- 8574081
TI  - Brain death: the family in crisis.
AB  - Brain death has created a new class of dead people that does not conform to
      society's expectations of normal death and dying. Brain death also causes intense
      emotions and great stress for the family and friends of the person concerned.
      Nurses play a major role in helping the family through this distressing time by
      maintaining high standards of nursing care. Major components of this care include
      effective communication and caring that supports the family. While these families
      have a variety of special needs, it is the nurses' constant bedside presence that
      provides many opportunities to have a positive influence on family members'
      ability to cope with the tragedy and begin the healing process.

PMID- 8574082
TI  - Nursing management of congestive heart failure. Part 2.

PMID- 8574083
TI  - Post-intensive care interviews: implications for future practice.
AB  - The measurement of outcome from intensive care, including the long-term
      physiological and psychological effects of disease and intensive therapy has
      tended to receive scanty attention. Little consideration has been given to the
      implications this may have for the patients, relatives and for future practice.
      Patients were interviewed in their own homes after 6 months of recovery, to allow
      freedom of expression and comfort within their own environment (territory). This
      study demonstrates that data generated by face-to-face interviews can be of
      immense importance to intensivists in assessing the effectiveness of services and
      promoting changes in clinical practice. It also shows a need for a long-term
      follow-up service encompassing community and hospital.

PMID- 8574084
TI  - Reducing relocation stress after discharge from the intensive therapy unit.
AB  - Moving from the intensive therapy unit (ITU) to the ward environment can be a
      very stressful experience for patients. Nursing interventions can help to reduce
      the stress associated with this experience and help each patient to cope with it.
      The factors which cause relocation stress are discussed along with a strategy
      employed clinically to reduce or prevent this problem in patients after discharge
      from an ITU.

PMID- 8574085
TI  - Oxygen free radicals: in search of a unifying theory of disease.
AB  - The purpose of this paper is to examine the subject of oxygen free radicals and
      the damage they do in the human body, providing understanding of the basic
      principles involved, while at the same time highlighting areas of debate relevant
      to nurses working in critical care areas. Links to various areas of disease are
      explored, including coronary artery disease, cancer and reperfusion injuries.
      Ageing is also discussed. The role of antioxidant therapy is examined, as is the
      need for further research of the subject in general.

PMID- 8574086
TI  - 'Take me away from all this' ... can reminiscence be therapeutic in an intensive
      care unit?
AB  - 'Stuart had been with us in the ICU for 4 weeks; weaning attempts from his
      artificial ventilation were difficult, leaving him frightened, exhausted and
      despondent. Depression, hopelessness and apathy were beginning to take a hold on
      him ... until one day something changed everything. A way had been found to help
      him escape, temporarily, from his intensive care situation. Three days later
      Stuart was breathing spontaneously and was being prepared for discharge from the
      ICU.' In this paper potential benefits of reminiscence sessions with patients in
      a critical care unit are discussed. Background and context are reviewed, leading
      to some suggestions for practice.

PMID- 8574087
TI  - A pressure sore risk calculator for intensive care patients: 'the Sunderland
      experience'.
AB  - Pressure sore risk calculators have been identified as a useful tool in the
      preventative management of pressure sore development. Cubbin & Jackson (1991)
      believed that none of the many existing calculators were appropriate for the
      critically ill patients in intensive therapy units and adjusted an existing
      calculator to meet the needs of their patients. The Sunderland experience is a
      detailed account of a study which included a trial of Cubbin & Jackson's
      calculator, a critical analysis of the assessment criteria, and trial of a
      modified risk calculator. As accurate identification of at-risk patients
      increased the economic problem of supply/demand of specialised beds to reduce the
      risk of pressure sores raised many issues throughout the department. The study
      also included introduction of a wound management protocol and an efficient
      documentation system which has improved communication and continuity of care.

PMID- 8574088
TI  - Auditing quality of nursing care.
AB  - Nurses working in intensive therapy units (ITU) may perceive that they provide a
      good quality of nursing care to patients and relatives in the ITU. But how can
      this be assessed, to enable nurses to have an indication of the actual quality of
      nursing care? This article examines quality and audit within nursing, and then
      examines one of the commercially produced tools that can be utilised to give an
      indication of the nursing care provided within the ITU. The results of a part
      pilot study are imparted and then further discussed. ITU nurses need to be aware
      that if they do not commence auditing their nursing care then someone with no
      specialist knowledge may dictate to them what to do to audit their care.

PMID- 8574089
TI  - Fentanyl transdermal (durogesic, Janssen).
AB  - Fentanyl is a potent opioid analgesic with a characteristically brief duration of
      action. Its formulation in a transdermal patch provides a novel method of
      delivering continuous analgesia for patients with prolonged or chronic pain.

PMID- 8574090
TI  - Mucosal surface ferricyanide reductase activity in mouse duodenum.
AB  - Mouse duodenum possesses mucosal surface ferricyanide reductase activity. The
      reducing activity, determined in vitro by measuring ferrocyanide production from
      ferricyanide, was found to be greater in duodenal fragments when compared with
      ileal fragments. Experiments with right-side out tied-off duodenal sacs show that
      reduction occurs mainly on the mucosal side and indicates that the reducing
      activity is associated with the brush border membrane. Experiments using mice
      with increased levels of iron absorption (hypoxic, iron-deficient) showed
      corresponding increases in reducing activity. The increase was present in
      duodenal but not ileal fragments. Inhibitor studies showed no effect of several
      compounds which inhibit other, more characterized, transplasma membrane
      reductases. In particular, doxorubicin (10 microM) and quinacrine (1mM) were
      without effect on duodenal mucosal transplasma membrane reducing activity.
      Depolarization of the membrane potential with high medium K+ inhibited reducing
      activity. N-ethyl malemide (1 mM) was a potent inhibitor, but iodoacetate was
      found to be less inhibitory. Comparison with inhibitory effects on glyceraldehyde
      3-phosphate dehydrogenase (GAPDH) demonstrated that the effect of N-ethyl
      malemide on reducing activity was not secondary to GAPDH. Collectively these
      results indicate that mouse duodenum possesses mucosal surface transplasma
      membrane ferricyanide reductase activity and that the activity is correlated with
      the process of intestinal iron absorption. Furthermore, the reducing activity
      appears to be distinct from other reported transplasma membrane reductases.

PMID- 8574091
TI  - Cation-dependent uptake of zinc in human fibroblasts.
AB  - The influence of K+ and Ca2+ on Zn2+ transport into cultured human fibroblasts
      was investigated. Zn2+ uptake was markedly reduced in the presence of both
      valinomycin and nigericin (electrogenic and electroneutral K+ ionophores,
      respectively), and by reduction in the transmembrane K+ gradient produced by
      replacement of extracellular K+ with Na+, suggesting that Zn2+ may be driven by a
      Zn2+/K+ counter-transport system. To test the counter-transport hypothesis, we
      used 86Rb as an analog of K+ for efflux studies. The rate of Rb+ efflux was 3760
      times that of Zn2+ uptake, thus the component of K+ involved in the Zn2+ counter
      transport system was only a small proportion of the total K+ efflux. In
      investigating the effect of Ca2+ on Zn2+ uptake, we identified two components:
      (1) a basal Zn2+ uptake pathway, independent of hormonal or growth factors which
      does not require extracellular Ca2+ and (2) a Ca(2+)-dependent mechanism. The
      absence of Ca2+ decreased Zn2+ uptake, while increasing extracellular Ca2+
      stimulated Zn2+ uptake. The effect was mediated by Ca2+ influx as the ionophores
      A23187 and ionomycin also stimulated Zn2+ uptake. We could not ascribe the Ca2+
      effect to known Ca2+ influx pathways. We conclude that Zn2+ uptake occurs by a
      K(+)-dependent process, possibly by Zn2+/K+ counter-transport and that a
      component of this is also Ca(2+)-dependent.

PMID- 8574092
TI  - Copper-glutathione complexes under physiological conditions: structures in
      solution different from the solid state coordination.
AB  - The physiologically important copper complexes of oxidized glutathione have been
      examined by electron spin resonance (ESR) spectroscopy in aqueous solution at
      neutral pH. Low temperature measurements show that the Cu(II) binding site in
      oxidized glutathione has the same ligand arrangement as in copper complexes of S
      methylglutathione, glutamine, glutamate and glycine. The site is composed of the
      amino nitrogens and the carboxyl oxygens of two gamma-glutamyl residues; there is
      no interaction with amide nitrogens, the sulphur bond or the glycyl carboxyl
      groups. At high metal to ligand ratios a binuclear species exists, in which each
      Cu(II) binds only to one gamma-glutamyl residue. The previously reported
      forbidden transition detected at g = 4 is due to non-specific aggregation and not
      to spin coupling of intramolecular sites. Liquid solution ESR spectra show the
      Cu(II)-glutathione complex has a lower mobility than the corresponding Cu(II)-S
      methylglutathione species. From the degree of spectral anisotropy the complex
      with glutathione is calculated to exist as a dimer. These results demonstrate
      that the physiologically relevant complex between copper and oxidized glutathione
      in solution is completely different from the known solid state structure
      determined by crystallography.

PMID- 8574093
TI  - The application of laser microprobe mass analysis to the study of biological
      material.
AB  - Laser microprobe mass analysis (LAMMA) is an investigational method which is a
      powerful tool for the identification and quantitation of various elements present
      in small volumes of tissue. LAMMA is highly sensitive and capable of rapidly
      detecting concentrations of 1-3 p.p.m. of most metallic elements, in precisely
      localized cellular compartments. In order to further assess its value, cultured
      skin fibroblasts and biopsy tissues from human subjects and experimental animals
      were probed by LAMMA, and the results were correlated with ultrastructural
      findings. Biopsy samples were obtained from patients suffering from Gaucher
      disease, and from patients and animals with pathologic iron or copper metabolism.
      No significant abnormalities were detected in the cultured fibroblasts from
      patients with Gaucher disease, in contrast to the iron content of tissue biopsy
      Gaucher cells, which was markedly increased, apparently as a consequence of
      erythrophagocytosis. Particularly intense iron-related peaks were found in liver
      cytosiderosis due to neonatal or genetic haemochromatosis, thalassaemia major and
      in animal models of iron overload. An additional finding was the presence of
      aluminium accumulation in siderosomes of different cells. In liver biopsy samples
      from human Wilson's disease and from rats with an inherited disorder causing
      copper toxicosis, copper-containing compounds were identified and localized, and
      their relative concentration was estimated by LAMMA. The present study showed
      that LAMMA is a valuable technique for the localization and estimation of
      relative abundance of trace elements in various tissues containing excessive
      amounts of metals.

PMID- 8574095
TI  - Characterization of a novel Spirillum-like bacterium that degrades ferrioxamine
      type siderophores.
AB  - A novel Gram-negative Spirillum-like bacterium (ASP-1) was isolated from lake
      water by enrichment culture on desferrioxamine B as sole source of carbon and
      energy. ASP-1 was able to degrade the siderophores desferrioxamine B and E. The
      property of siderophore degradation was inducible in the presence of
      desferrioxamine B. The ferric complexes, however, were not measurably degraded
      but served as an iron source. Degradation of desferrioxamines in culture was
      followed by measuring the residual ferrioxamines colorimetrically at 430 nm after
      addition of iron. Degradation in cell-free assays was followed quantitatively by
      HPLC on a reversed-phase column measuring the time-dependent disappearance of the
      desferrioxamines B and E. Cell-free assays also revealed that degradation of the
      cyclic desferrioxamine E was rapid and complete, whereas degradation of the
      linear desferrioxamine B yielded two intermediate iron-binding metabolites of
      shorter chain length. Preparative isolation by HPLC and mass spectrometric
      analysis of the metabolites revealed masses at 361 and 419 a.m.u., respectively,
      suggesting a splitting at the two amide bonds. ASP-1 is a nitrogen fixing
      Spirillum bacterium which could also use ammonium and glucose or several organic
      acids as a carbon source but grew poorly with amino acids. Physiological
      comparisons with Aquaspirillum and Azospirillum failed to assign ASP-1 to any of
      the presently known Spirillum species. Based on 16S rDNA sequence analysis the
      strain could be placed within the radiation of the Azospirillum/Rhodocista group.
      The closest relative was Azospirillum irakense, showing 98.8% similarity.

PMID- 8574096
TI  - Electron paramagnetic resonance studies and effects of vanadium in Saccharomyces
      cerevisiae.
AB  - Vanadium uptake by whole cells and isolated cell walls of the yeast Saccharomyces
      cerevisiae was studied. When orthovanadate was added to wild-type S. cerevisiae
      cells growing in rich medium, growth was inhibited as a function of the VO4(3-)
      concentration and the growth was completely arrested at a concentration of 20 mM
      of VO4(3-) in YEPD. Electron paramagnetic resonance (EPR) spectroscopy was used
      to obtain structural and dynamic information about the cell-associated
      paramagnetic vanadyl ion. The presence of EPR signals indicated that vanadate was
      reduced by whole cells to the vanadyl ion. On the contrary, no EPR signals were
      detected after interaction of vanadate with isolated cell walls. A 'mobile' and
      an 'immobile' species associated in cells with small chelates and with
      macromolecular sites, respectively, were identified. The value of rational
      correlation time tau r indicated the relative motional freedom at the
      macromolecular site. A strongly 'immobilized' vanadyl species bound to polar
      sites mainly through coulombic attractions was detected after interaction of VO2+
      ions with isolated cell walls.

PMID- 8574094
TI  - Divalent cation binding to ceruloplasmin.
AB  - Binding of calcium to human and sheep ceruloplasmin was investigated by metal
      substitution with manganese and competitive displacement of bound manganese by
      calcium monitored by electron paramagnetic resonance spectroscopy. The Kd for
      calcium was found to be 1.4 mM. Magnesium also bound to ceruloplasmin, with Kd =
      0.3 and 0.7 mM for the human and sheep protein, respectively. The thermal
      stability of ceruloplasmin, as studied by differential scanning calorimetry, was
      affected by calcium but not by magnesium. A considerable increase of the Tm
      value, from 73.8 to 83.1 degrees C, was observed for sheep ceruloplasmin in the
      presence of calcium. The Tm value of the human protein was only slightly altered
      by calcium (from 85.1 to 87 degrees C). The interaction of ceruloplasmin with the
      chromatographic material used for its isolation, Sepharose 4B derivatized with
      chloroethylamine, was weakened by calcium. This allowed us to set up a novel
      purification scheme that made it possible to efficiently isolate ceruloplasmin
      and prothrombin from plasma with the same single-step chromatography.

PMID- 8574098
TI  - Has the patient's charter improved A&E services?

PMID- 8574097
TI  - 'Free' iron, as detected by electron paramagnetic resonance spectroscopy,
      increases unequally in different tissues during dietary iron overload in the rat.
AB  - 'Free' iron concentration, as determined by electron paramagnetic resonance (EPR)
      spectroscopy, and lipid peroxidation (LPO), as determined by thiobarbituric acid
      test, were assessed in the lung, heart, liver, spleen, brain and kidney of rats
      subjected to experimental iron overload. Two tests, Desferal- and NO-available
      iron, were used to measure 'free' iron and gave comparable results. The most
      pronounced accumulation of 'free' iron was observed in liver, kidney and spleen.
      Differences between control and iron loaded animals increased during the initial
      90 days of treatment. Between 90 and 180 days 'free' iron concentration reached a
      steady state level, or even decreased, as in the case of liver. Lipid
      peroxidation level, measured in the organs of both treated and matched controls,
      did not give any significant difference during the initial 90 days of treatment.
      A significant augmentation was observed in liver, kidney, spleen and heart at 180
      days. The results of the present research show that, under conditions of moderate
      siderosis, the occurrence of LPO is partially related to the level of 'free'
      iron.

PMID- 8574099
TI  - Why do nurses agree to take on doctors' roles?

PMID- 8574100
TI  - The training of nurse surgical assistants.
AB  - This article discusses the development and training of nurse surgical assistants
      within the Royal Berkshire and Battle Hospitals NHS Trust. The training used the
      National Vocational Qualification (NVQ) framework to facilitate application for
      accreditation of prior knowledge in any future NVQ award.

PMID- 8574101
TI  - Transfer anxiety in patients with myocardial infarction.
AB  - When patients are transferred from a coronary care unit to a general ward they
      often experience transfer anxiety. A structured pre-transfer teaching programme
      is suggested as a tool which may improve patient care.

PMID- 8574102
TI  - Caring for the 'new' family in palliative care.
AB  - A knowledge of societal changes within the family and bereavement theories
      increases the nurse's understanding of the loved ones' needs in palliative care.
      The encouragement of self-awareness and reflective practice facilitates staff to
      support the new family or patient's partner effectively.

PMID- 8574103
TI  - The value of mental health nursing.

PMID- 8574105
TI  - Development and application of social learning theory.
AB  - This article traces the development of social learning theory over the last 30
      years, relating the developments to clinical nursing practice. Particular
      attention is focused on the contribution of Albert Bandura, the American
      psychologist, and his work on modelling.

PMID- 8574104
TI  - Dissemination and application of mental health nursing research.
AB  - Various government reports recognize that research is not informing practice.
      This article discusses the reasons for this and what organizations and
      individuals can do about it.

PMID- 8574106
TI  - Interaction analysis: a therapeutic tool.

PMID- 8574107
TI  - Self-empowerment in health promotion: a realistic target?
AB  - There have been many calls for nurses to adopt a self-empowerment model for
      health promotion practice rather than continuing to work from the medical model.
      Continuing with our series on health promotion, this article examines features of
      the self-empowerment approach and questions whether its goals are achievable.

PMID- 8574108
TI  - Has The Scope of Professional Practice failed in its original aim?

PMID- 8574109
TI  - Impact of The Patient's Charter on A&E departments: 1.
AB  - In the first of a two-part series presenting the results of a national survey of
      senior nurses in accident and emergency (A&E) departments, developments in the
      delivery of nursing care are examined within the context of the major
      organizational changes within the NHS since 1990; in particular, the requirements
      of meeting The Patient's Charter (Department of Health, 1991, 1995a) standards
      are discussed. The second article in this series will examine the developing role
      of the nurse practitioner in A&E departments.

PMID- 8574110
TI  - Physicians can reduce the incidence of domestic violence.

PMID- 8574111
TI  - Family violence: practical recommendations for physicians and the medical
      community.

PMID- 8574112
TI  - Women's experiences with battering: a conceptualization from qualitative
      research.

PMID- 8574113
TI  - Project SAFE: domestic violence education for practicing physicians.

PMID- 8574114
TI  - WomanKind: an innovative model of health care response to domestic abuse.

PMID- 8574115
TI  - Domestic violence and the politics of a statewide community.

PMID- 8574116
TI  - Florida physician and nurse education and practice related to domestic violence.

PMID- 8574117
TI  - Mandatory reporting of domestic violence by health care providers: a misguided
      approach.

PMID- 8574118
TI  - The influence of abuse on pregnancy intention.

PMID- 8574120
TI  - An update on the Jacobs Institute of Women's Health.

PMID- 8574119
TI  - The primary health care provider's role in sexual assault prevention.

PMID- 8574121
TI  - CO2 retention during hyperbaric exercise while breathing 40/60 nitrox.
AB  - We evaluated CO2 retention in 24 Navy construction divers breathing air at 1 atm
      abs (101.3 kPa) and 40% O2 (40/60) nitrox at 4 atm abs (Po2 of 162.1 kPa) inside
      a pressure chamber. The divers sat immersed to the sternal notch and exercised
      against pneumatically loaded pedals at a Vo2 of approximately 1.3 liter/min. The
      mean end-tidal CO2 tension (PET(CO2)2) at 1 atm abs (45.7 +/- 5.0 SD torr) was
      significantly higher than that of non-divers and diving trainees (40 +/- 5.0) but
      did not increase significantly at depth (47.1 +/- 6.3). The ranking of CO2
      retention was not maintained at depth. Unpredictable upward and downward shifts
      of up to 10 torr occurred in some divers. The PET(CO2) of six of the divers at
      pressure was greater than 50 torr, which based on animal studies markedly
      increases the risk of central nervous system oxygen toxicity. We translated their
      values into individual depth limits with 40/60 nitrox: three with 50 < PET(CO2) <
      55 torr were forbidden to dive beyond 25 m and three with values > 55 torr were
      restricted to 20 m. We propose that whenever possible, PET(CO2) during exercise
      at pressure be measured in potential nitrox users and that the above PO2 limits
      be enforced on moderate and extreme CO2 retainers, respectively.

PMID- 8574122
TI  - Effects of venous gas microemboli on pulmonary gas transfer function.
AB  - Dynamic lung volumes and flows, slope of phase III of the single breath oxygen
      test (delta-N2), closing volume (CV), and transfer factor for carbon monoxide
      (TICO) were measured before and 1 h after an air dive in a hyperbaric chamber to
      a pressure of 0.49 MPa for 40 min. Six divers had a bottom time of 20 min and a
      rate of decompression of 50 kPa x min-1, and six divers had a bottom time of 24
      min and a rate of decompression of 100 kPa x min-1. Decompression stops were 5
      min at 0.16 MPa and 10 min at 0.13 MPa for both groups. As control exposure they
      were breathing O2 at atmospheric pressure for 40 min. The dive and control
      exposure were done on different days within 1 wk, in random order. Doppler
      ultrasound monitoring for venous gas microemboli (VGM) was done during the first
      hour after the dive. VGM were detectable in all six divers with the fast
      decompression rate and in one subject with the slow rate (P < 0.01). In the
      subjects having VGM there was a significant reduction in TICO of -5.9 +/- 4.4%
      compared with -0.5 +/- 3.4% after the control exposure (P = 0.034). In the five
      subjects without detectable VGM, the changes in TICO were -2.8 +/- 3.7% and 0.2
      +/- 3.8%, respectively. There were no significant changes in dynamic lung volumes
      and flows, CV, or delta-N2. A reduction in TICO may reflect effects of VGM after
      dives in which the effect of O2 exposure is negligible.

PMID- 8574123
TI  - Effect of SF6-O2 (80/20) breathing on air bubbles in rat tissues.
AB  - We studied the effect of SF6-O2 breathing on air bubbles injected into skeletal
      muscle, rat-tail tendon, the anterior chamber of the eye, and spinal white
      matter. Decompression-induced nitrogen bubbles in adipose tissue were studied
      during breathing of SF6-O2 (80/20). The results of SF6-O2 breathing are compared
      with previous experiments using heliox (80/20) as the breathing medium. Bubbles
      studied in skeletal muscle, eye chamber, and spinal white matter were found to
      behave in a two-phased manner during SF6-O2 (80/20) breathing. All bubbles would
      initially decrease rapidly in size for a period of 10-80 min (depending on the
      tissue). Subsequently, the bubbles stabilized and decreased in size with a
      shrinking rate near zero. In spinal white matter, very small bubbles decreased
      size with a shrinking rate near zero. In spinal white matter, very small bubbles
      could disappear before development of the slow phase. All bubbles in tendon
      shrank at a rather constant rate during SF6-O2 (80/20) breathing until they
      disappeared. During SF6-O2 (80/20) breathing, all bubbles in adipose tissue
      shrank and disappeared at least as fast as during heliox (80/20) breathing. Just
      before disappearance of the bubbles the shrinking rate slowed. Comparison of the
      effects of SF6-O2 (80/20) and heliox (80/20) breathing suggests that
      countercurrent gas exchange is at work in some tissues.

PMID- 8574124
TI  - Ascent rate, post-dive exercise, and decompression sickness in the rat.
AB  - The effects of ascent rate and post-dive exercise on the incidence of
      decompression sickness (DCS) were investigated in six groups of 20 rats exposed
      for 2 h at a pressure equivalent to 240 feet of sea water (fsw; 735 kPa). Ascent
      rates were 30, 45, and 60 fsw/min (92, 138, 184 kPa/min), and the rats either
      rested after the exposure or exercised by walking for 30 min on a treadmill at
      1.6 m/min. Post-dive signs included respiratory distress, difficulty walking,
      paralysis, and death. DCS was scored as non-fatal at 30-min post-dive or fatal at
      any time. Analysis by ordinal logistic regression indicated more DCS with post
      dive exercise (P = 0.0112) and at 45 (P = 0.0011) and 60 fsw/min (P = 0.0001)
      compared to 30 fsw/min. Survival analysis suggested earlier death at 60 fsw/min
      compared to 30 fsw/min (P = 0.0006). Similar effects have been reported for the
      less severe DCS that occurs in humans.

PMID- 8574125
TI  - Inhibition of nitric oxide synthase on brain oxygenation in anesthetized rats
      exposed to hyperbaric oxygen.
AB  - Nitric oxide (NO) production is involved in the development of oxygen toxicity of
      the central nervous system (CNS) since inhibition of nitric oxide synthase (NOS)
      significantly protects animals from hyperbaric oxygen (HBO)-mediated convulsions.
      One potential mechanism for this protection is that NOS inhibition decreases
      cerebral O2 delivery thereby limiting the PO2 of brain tissues during hyperoxia.
      To investigate this hypothesis, anesthetized rats were exposed to 7, 100, and 7%
      O2 under 3 atm abs for 15-min periods. Cortical blood flow (CBF) and O2 tension
      were measured with a laser-Doppler flowprobe and an O2 electrode, respectively,
      with and without pretreatment with the NOS doppler, N omega-nitro-L-arginine
      methyl ester (L-NAME). We found that HBO exposure significantly increased the
      brain O2 tension whereas changes in CBF were not significant. Compared with
      control rats, L-NAME administration did not change either brain O2 tension or CBF
      during the period of the experiment. We conclude that the effects of L-NAME on
      cortical oxygenation and CBF during HBO exposure in rats do not seem to provide a
      physiologic explanation for protection from CNS O2 toxicity by the drug.

PMID- 8574126
TI  - Hyperbaric oxygen as an adjunctive treatment for delayed radiation injury of the
      chest wall: a retrospective review of twenty-three cases.
AB  - Since 1979, 23 cases of radiation-induced chest wall necrosis have been treated
      in the Hyperbaric Medicine Departments of Southwest Texas Methodist Hospital and
      the Nix Hospital, San Antonio, Texas. Eight cases involved soft tissue only. Six
      of eight (75%) patients with soft tissue involvement healed without requiring
      surgical debridement, although four patients (50%) did have flaps or grafts.
      Fifteen patients had bony and soft tissue necrosis. Eight of these patients (53%)
      resolved with adjunctive hyperbaric oxygen (HBO), but all required aggressive
      surgical debridement including skeletal resection. Four (27%) had reconstructive
      flaps as well. Six patients (40%) with bony necrosis who had either no or
      incomplete debridement failed to heal. Three patients (13%)(two soft tissue and
      one bony) were found to have residual tumor during HBO and were discontinued from
      treatment. HBO is an effective adjunctive therapy for soft tissue chest-wall,
      radiation-induced necrosis, but must be coupled with appropriate debridement to
      include surgical removal of all necrotic bone to ensure a successful outcome of
      bony plus soft tissue necrosis.

PMID- 8574127
TI  - Skin allograft rejection and hyperbaric oxygen treatment in immune
      histoincompatible mice.
AB  - The effect of hyperbaric oxygen (HBO) as an immunosuppressive agent was evaluated
      by using a highly immunogenic skin allograft mouse model. Immune
      histoincompatible female C57BL/6 and BALB/c mice (N = 30) were randomly assigned
      to three groups receiving no treatment (control group), low dose HBO treatment
      (two treatments once a week), and intermediate HBO treatment (two treatments 3
      times/wk) 1 wk before and 2 wk after transplantation of a 1.5 x 2 cm full
      thickness skin allograft from the back. Rejection was observed a Day 7 and was
      completed 14 days after surgery in controls. Low dose and intermediate HBO
      treatment delayed skin allograft rejection, which was histologically confirmed.

PMID- 8574128
TI  - Neuropsychologic and cardiovascular effects of clemastine fumarate under
      pressure.
AB  - Allergic rhinitis and mild respiratory infections have been widely accepted as
      temporary contraindications for fitness to dive. Nonetheless, several sport and
      professional divers use antihistamines to ease ear, nose, and throat (ENT)
      problems, especially for opening tubal ostium. Some divers know they are unfit to
      dive, but for a variety of reasons (e.g., money or short holiday) they try to
      clear their ears. Thus, the use of antihistaminic drugs (like clemastine
      fumarate) is common during diving. This double-blind, crossover study indicates
      that this special antihistamine does not increase the sedative effects of
      nitrogen narcosis, nor does it increase the level of cardiac arrhythmias. Liberal
      use of antihistamines while diving cannot be recommended because of possible
      complications connected with different preparations and the temporary limitations
      they impose on the diver.

PMID- 8574129
TI  - Hyperbaric oxygen and the reflex sympathetic dystrophy syndrome: a case report.
AB  - A patient suffering from acute smoke inhalation also had a long medical history
      that included reflex sympathetic dystrophy syndrome of the left foot and ankle.
      The entire foot and ankle were tender and cool to palpation; range of motion was
      severely reduced. She was referred for hyperbaric oxygen therapy, and 15 min into
      the the first treatment (46 min at 60 fsw) she reported a lessening of the pain
      in her foot; moreover, the foot was less cyanotic and warmer to the touch.
      Subsequent treatments continued to improve her conditions and for longer periods
      of time.

PMID- 8574130
TI  - Dam-like methylation in legionellae.
AB  - The chromosomal DNA of a variety of legionellae, including clinical,
      environmental, and plasmid-containing strains, was examined for evidence of Dam
      like methylation. It was found that Dam-like methylation was present in all the
      strains examined regardless of their origin or plasmid content.

PMID- 8574131
TI  - Identification and discrimination of oral asaccharolytic Eubacterium spp. by
      pyrolysis mass spectrometry and artificial neural networks.
AB  - Curie-point pyrolysis mass spectra were obtained from 29 oral asaccharolytic
      Eubacterium strains and 6 abscess isolates previously identified as
      Peptostreptococcus heliotrinreducens. Pyrolysis mass spectrometry (PyMS) with
      cluster analysis was able to clarify the taxonomic position of this group of
      organisms. Artificial neural networks (ANNS) were then trained by supervised
      learning (with the back-propagation algorithm) to recognize the strains from
      their pyrolysis mass spectra; all Eubacterium strains were correctly identified,
      and the abscess isolates were identified as un-named Eubacterium taxon C2 and
      were distinct from the type strain of P. heliotrinreducens. These results
      demonstrate that the combination of PyMS and ANNs provides a rapid and accurate
      identification technique.

PMID- 8574132
TI  - Enterococcus seriolicida is a junior synonym of Lactococcus garvieae, a causative
      agent of septicemia and meningoencephalitis in fish.
AB  - The reference strains of Enterococcus seriolicida (ATCC 49156T) (T = type strain)
      and of Lactococcus garvieae (ATCC 43921T) and 30 field strains of Gram-positive
      cocci isolated from diseased rainbow trout in Italy were found to be
      phenotypically (API 20 STREPT and API 50 CH) and genetically (DNA-DNA
      hybridization) similar. The high DNA-DNA homologies (70-100%) and the low delta
      Tme (less than 1.1 degrees C) among these strains showed that Enterococcus
      seriolicida and Lactococcus garvieae are synonyms, describing a single bacterial
      species. E. seriolicida strains should be classified as L. garvieae, which must
      be considered as a major pathogen of freshwater and salt water fish with a world
      wide distribution.

PMID- 8574133
TI  - Ribosomal protein S1 (RpsA) of Buchnera aphidicola, the endosymbiont of aphids:
      characterization of the gene and detection of the product.
AB  - Buchnera aphidicola is a prokaryotic endosymbiont found in specialized cells of
      the aphid Schizaphis graminum. Many of the previously cloned B. aphidicola genes
      are preceded by a poor ribosome-binding site. Ribosomal protein S1 (RpsA) allows
      the translation of messenger RNAs that lack or have a poor ribosome binding site.
      We have cloned and sequenced a 4.5-kilobase (kb) B. aphidicola DNA fragment
      containing four open reading frames corresponding to aroA-rpsA-himD-tpiA. The
      deduced amino acid sequence of B. aphidicola RpsA was 75% identical to that of
      the Escherichia coli protein. The major difference was in the number of basic
      amino acids, which were present in higher numbers in B. aphidicola RpsA.
      Antiserum to E. coli RpsA was prepared and used to detect B. aphidicola RpsA in
      cell-free extracts of aphids. During the first 12 days of aphid growth there is a
      slight decrease in the amount of RpsA per unit of aphid weight. The three
      additional genes found on the 4.5-kb DNA fragment encoded for proteins involved
      in aromatic amino acid biosynthesis (aroA), DNA bending (himD), and carbohydrate
      metabolism (tpiA). The presence of these genes in B. aphidicola is additional
      evidence of its similarity to free-living bacteria.

PMID- 8574134
TI  - DNA-binding activities in Streptococcus gordonii: identification of a receptor
      nickase and a histonelike protein.
AB  - Extraction of Streptococcus gordonii cells with the mild chaotropic agent, LiCl,
      drastically decreased DNA transforming ability, had little effect on viability,
      and released both DNA nicking and binding activities. Both activities were Mg2+
      and Ca2+ independent and were not competence specific. Southwestern blot analysis
      of the extract identified putative surface proteins of 56 kDa and 68 kDa in
      strain Challis and Wicky, respectively. Extracts also contained a 10-kDa DNA
      binding protein, designated HSgo, that belongs to the eubacterial histonelike
      class of proteins.

PMID- 8574135
TI  - Message from the director of the RCMI program.

PMID- 8574136
TI  - Special issue on AIDS.

PMID- 8574137
TI  - Synthesis and anti-HIV activity of steroidal prodrugs of 3'-azido-3'
      deoxythymidine (AZT).
AB  - A total of seven steroidal prodrugs of AZT were synthesized and tested in vitro
      for their anti-HIV activity. Three of them were steroidal carboxylic esters
      prepared from steroidal 17 beta-carboxylic acids and AZT. The remaining four were
      alkyl steroidal phospho-triesters of AZT. These prodrugs were synthesized using
      known procedures. Preliminary results of in vitro anti-HIV activity screening
      showed that all of these prodrugs were active against HIV. While carboxylic
      esters showed comparable anti-HIV activity to that of AZT, phosphotriesters were
      less active than AZT. The therapeutic indices of all these prodrugs are
      comparable to that of AZT.

PMID- 8574138
TI  - Zidovudine as an immunomodulatory agent.
AB  - In view of the increase of HIV infection in women, and of transplacental
      infectivity, 3'-azido-3'-deoxythymidine (zidovudine) is being explored to control
      infection in offspring. Zidovudine toxicity in humans and experimental animals is
      well documented. However, information on immunotoxicity in pregnant females and
      their offspring is lacking. We exposed pregnant female mice to zidovudine to
      provide data, and perhaps baseline evaluation, on zidovudine immunotoxicity in
      primiparous females and their progeny. In pregnant mice exposed to zidovudine
      (0.2 mg/ml) in drinking water, enhancement of the mixed lymphocyte response (MLR)
      occurs; suppression is not seen until the 7th month. Profound, persistent
      suppression is seen in their progeny first detected at one week of age.
      Suppression in virgin females occurs 1 month after treatment, which persists
      through the seventh month. The antibody forming cell response is enhanced in
      primiparous females and their offspring, but is not affected in virgin females.
      After weekly alternation of oral treatment with two 0.5 ml intravenous injections
      at 0.2 mg/ml, MLR suppression occurs after 1 month in primiparous females, while
      in their progeny and in virgins enhancement is seen first; in progeny suppression
      is observed at 3 months. Thus, zidovudine is immunosuppressive for T-cell
      mediated immunity and the kind of modulation is a function of treatment regimen.

PMID- 8574139
TI  - Uptake and distribution of 2',3'-dideoxyinosine and its derivatives in a human
      monocytoid cell line.
AB  - The dideoxynucleoside analogue 2',3'-dideoxyinosine (ddI) has been used in the
      clinic as an alternative drug to zidovudine (AZT) in the treatment of patients
      with the acquired immunodeficiency syndrome (AIDS). However, it shows significant
      and variable toxicity in patients. It is known that various dideoxynucleoside
      analogues can cause the termination of the DNA chain following incorporation of
      the corresponding triphosphate metabolite by the polymerases. In the case of ddI,
      the presumed active metabolite is 2',3'-dideoxyadenosine 5'-triphosphate (ddATP).
      In order to understand the molecular basis for the toxicity of ddI, we evaluated
      the relationship between the intracellular formation of ddATP, its incorporation
      into cellular DNA and the effects on the growth of U937 cells, a human monocytoid
      cell line. Dideoxyinosine was not significantly toxic to U937 cells at
      concentrations as high as 500 microM in a 72 hrs. growth inhibition assay. The
      results of the uptake of 3HddI in this cell line showed a proportional increase
      in total metabolites with increasing concentrations of the drug (1-20 microM)
      after a 24 hrs. exposure. Incubation with 10 microM 3HddI resulted in the
      formation of low levels of ddATP within a period of 2 hrs. A significant amount
      of ddI-derived radioactivity was found in both DNA and RNA after exposure to 10
      microM 3HddI for 24 to 72 hrs. However, no evidence of incorporation of ddATP
      into the cellular DNA fraction was obtained in these experimental conditions.
      Therefore, the lack of significant toxicity of ddI to U937 cells can be
      explained, at least in part, by its inability to incorporate ddATP into its
      cellular DNA at the doses studied.

PMID- 8574140
TI  - A new flow cytometric method for quantitative assessment of lymphocyte mitogenic
      potentials.
AB  - A new flow cytometric method was developed to quantitatively assess lymphocyte
      proliferation simultaneously for different subsets. The cells were stained with a
      fluorescent dye, PKH-26 and were stimulated with mitogens. The fluorescence
      intensities (FL2) of proliferating cells were measured by flow cytometry; and
      each subset was identified by the use of a monoclonal antibody (Mab)-fluorescein
      isothiocyanate (FITC) (FL1). FL2 histograms were then analyzed by the cell
      proliferation model based on the ModFit software (Verity). This new method
      revealed information which could not be obtained by conventional mitogen assays.
      For example, the CD4+ and the CD4- T-subsets responded to phytohemagglutinin
      (PHA) quite differently from each other and it was indicated that activation of
      one population could significantly alter the response of the other. In addition,
      even within a subset, all activated cells did not proliferate uniformly. Some
      cells divided only once while others underwent further cellular division during
      the same time period. The method is, therefore, invaluable for studying the
      nature and the extent of interactions between different cellular subsets within a
      culture.

PMID- 8574141
TI  - Anti-CD4 cytotoxic T lymphocyte (CTL) activity in HIV+ patients: flow cytometric
      analysis.
AB  - A new cell proliferation analysis by flow cytometry was applied to the mitogen
      induced cultures of peripheral blood mononuclear cells (PBMC) from either normal,
      healthy donors or those individuals who are infected by human immunodeficiency
      virus, type 1 (HIV-1). While phytohemagglutinin (PHA) stimulation of normal PBMC
      (nPBMC) yielded propagation of both CD4 (nCD4) and CD8 (nCD8) T cell subsets,
      similar activation of PBMC from certain HIV-1-infected individuals (HIV-PBMC)
      produced active proliferation of CD8 (HIV-CD8) cells but varying degrees of CD4
      (HIV-CD4) cell destruction. However, no measurable viral p24 antigen was produced
      extracellularly. On the other hand, when the purified HIV-CD4 cells were
      similarly activated, no such cell death was noted and high titer p24 was detected
      in the culture supernatants. Addition of exogenous IL-2 to either HIV-PBMC or HIV
      CD4 cultures, did not alter either CD4 cell death or HIV-1 p24 production.
      Isolated HIV-CD8 killed not only HIV-CD4 but also nCD4, when co-cultured and less
      proliferative fractions of CD4 cell population was the more preferred targets of
      the HIV-CD8 CTL activity. The presence of anti-CD4 CTL activity was closely
      associated with high CD8, but not with CD4 counts, of the HIV+ patients.

PMID- 8574143
TI  - Calmodulin inhibitors and calcium channel blockers influence dideoxycytidine
      renal excretion.
AB  - Renal handling of 2',3'-dideoxycytidine (ddC), a new anti-HIV dideoxynucleoside
      which undergoes renal and non-renal clearance, was determined in CF-1 male mice.
      Since calmodulin inhibitors (CIs) and calcium channel blockers (CCBs) have been
      shown to influence the flux of pyrimidine nucleosides across mammalian membranes
      and since the plasma concentration (and hence the efficacy) of therapeutic
      nucleosides is usually affected by the rate of renal elimination, we decided to
      determine the impact of the CIs loperamide (LOP) and trifluoperazine (TFP) as
      well as the CCB verapamil (VER) on the renal excretion of ddC. The ratio of ddC
      clearance to inulin clearance suggests that ddC undergoes secretion into renal
      tubules. Pre-exposure of mice to the calmodulin inhibitors loperamide (LOP) and
      trifluoperazine (TFP) resulted in a decrease in ddC renal secretion while pre
      treatment with the calcium channel blocker verapamil increased ddC secretion.

PMID- 8574142
TI  - Molecular phylogeny and dissemination of human T-cell lymphotropic virus type I
      viewed within the context of primate evolution and human migration.
AB  - A renewed interest in the emergence and evolution of the primate T-cell
      lymphotropic viruses has followed the discovery of genetically distinct variants
      of human T-cell lymphotropic virus type I (HTLV-I) in Melanesia and Australia.
      Phylogenetic trees based on selected regions of the gag, pol, env and pX genes of
      HTLV-I from widely separated geographic regions and of simian T-cell lymphotropic
      virus type I (STLV-I) from African and Asian catarrhines, constructed using the
      neighbor-joining and maximum parsimony methods, indicated that the Australo
      Melanesian and cosmopolitan strains of HTLV-I have evolved along separate
      geographically dependent lineages, with African STLV-I strains clustering with
      cosmopolitan HTLV-I strains and Asian STLV-I strains diverging from the common
      ancestral virus before the Australo-Melanesian HTLV-I strains. When viewed within
      the context of non-human primate evolution and human occupation of Australia and
      Melanesia, the rate of molecular change of HTLV-I and STLV-I is approximately 2.5
      6.8 x 10(-7) substitutions per site per year. Overall, the sequence and
      phylogenetic analyses are in accord with interspecies virus transmission among
      non-human primates, as well as between non-human primates and humans, with
      independent evolution of HTLV-I in Southeast Asia and in Africa, and with
      dissemination of HTLV-I by forced or voluntary movements of human populations.
      The immunosuppressive and T-cell activation properties of HTLV-I places at added
      risk these Australian Aboriginal and Melanesian populations, some of which are in
      imminent threat of infection with human immunodeficiency virus type 1.

PMID- 8574144
TI  - Prevalence of enteric parasitic infection among HIV-infected attendees of an
      inner city AIDS clinic.
AB  - One hundred individuals confirmed to be infected with the human immunodeficiency
      virus (HIV), volunteered to participate in a pilot study comparing clinical
      status and enteric parasite burden with race, age, CD4 levels, risk factors and
      sexual practice. The prevalence of enteric parasites was 55 (55%) for Giardia
      lamblia, 6 (6%) for Cryptosporidium, 10 (10%) for Isospora belli and 3 (3%) for
      Entamoeba histolytica. There was no associations between demographic variables
      and the presence of parasites. The presence of giardia was significantly
      associated with anal-penile sex (P = .017), with an odds ratio of 2.9. A logistic
      regression model was used to explain the presence of any parasite by a number of
      sexual practices. The only practice found to be significant was anal-penile sex,
      which substantially increased the likelihood of the presence of the parasites. In
      this regression, 38.5% of pairs were concordant and 12.2% were discordant. These
      findings differed from surveys conducted in similar populations. The significance
      of this will be discussed in the context of medical service provision to this and
      similar populations.

PMID- 8574145
TI  - Suppressed proliferative response and interleukin-2 production in hispanic HIV+
      and AIDS T-cell subsets.
AB  - We find that interleukin-2 (IL-2) production is severely depressed (80-90%) in
      AIDS T-cells (CD4+ or CD8+) stimulated with anti-CD3 or Con A together with
      phorbol ester (PMA) or anti-CD28 coactivation. Likewise, the proliferative
      response of CD4+ T-cells was suppressed, from a mean of 24.6% (HIV+) to 59.1%
      (AIDS) for PMA with activators OKT3 (anti-CD3), Con A, enterotoxin B or pokeweed
      mitogen, and 20.2% (HIV+) to 77.8% (AIDS) with anti-CD28 co-activation. Similar
      degrees of suppression were found with the CD8+ T-cells except for a much greater
      suppression at the HIV+ stage with anti-CD28 (57.7%), approximately 2.5 times
      higher than for PMA coactivation. However, when proliferation was induced by the
      two coactivators combined (PMA plus anti-CD28), much less suppression was
      observed: 8.5% (HIV+) to 19.0% (AIDS) for CD4+ cells and 8.2% to 26.5%,
      respectively, for CD8+ cells. The data suggest that during HIV infection the CD28
      pathway becomes most defective, but can be bypassed to some extent by the less
      impaired PMA pathway. The IL-2 (+PMA) signal in HIV+ and AIDS cells was also
      significantly less suppressed suggesting that the disregulation in HIV infection
      is more prominent prior to the IL-2 stage of the mitogenic pathway. It is
      remarkable that the CD4+ and CD8+ T-cells at both the HIV+ and AIDS stages
      generally show the same degree of suppression with all the various activators and
      coactivators used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574146
TI  - N-acetylcysteine (NAC) enhances interleukin-2 but suppresses interleukin-4
      secretion from normal and HIV+ CD4+ T-cells.
AB  - We find that purified CD4+ T cells from 30 HIV+ individuals have a suppressed
      Interleukin-4 (IL-4) production compared to normal controls regardless of
      activator (anti-CD3 or Con A) or co-activator [phorbol ester (PMA or anti-CD28)],
      generally by 2-4 fold. In every case, the cells producing IL-4 respond more
      strongly to anti-CD28 co-activation than to PMA, ie, 1150 pg/ml compared to 2070
      pg/ml for controls and 398 pg/ml compared to 1250 pg/ml for HIV+ cells,
      respectively. In contrast, anti-CD3 with PMA gives a more vigorous IL-2 response
      than with anti-CD28, ie, 37.3 ng/ml compared to 12.3 ng/ml for controls and 28.5
      ng/ml versus 15.1 ng/ml for HIV+ cells, respectively. These data are not
      compatible with the TH1/TH2 switch hypothesis since IL-4 production is decreased,
      not increased for CD4+ HIV+ T-cells and while IL-2 production is decreased with
      PMA, it is not decreased significantly with anti-CD28. Interestingly, 5 mM N
      acetylcysteine (NAC) acts as an immunoenhancer; mitogenesis was enhanced 2 fold
      or more in general for control and HIV+ CD4+ T-cells and IL-2 production was
      enhanced 2-3 fold for anti-CD3 (with PMA or anti-CD28) for both controls and HIV+
      CD4+ cells. However, NAC suppressed IL-4 production induced by anti-CD3 and anti
      CD28 in both control and HIV+ CD4+ T cells. In the other cases, it produced in
      general no significant change.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574148
TI  - HIV/AIDS in Costa Rica: epidemiological and sociological features, 1993.
AB  - Acquired immunodeficiency syndrome (AIDS) was first detected in Costa Rica in
      1983. For four years most known cases were in hemophiliac men. Thereafter, AIDS
      in homosexual and bisexual men predominated. By December 31 of 1993, 563 persons
      had been diagnosed with the syndrome, 71% of them homosexual and bisexual men,
      10% heterosexual men and women, 6% hemophiliacs, 2% intravenous drug abusers
      (IVDA's), 2% women and men who had blood transfusions, 1.4% infants born to HIV
      infected mothers and 7% unknown. The epidemics in homosexual/bisexual men and in
      heterosexual women and men are rising; cases in infants and in persons who
      received blood or coagulation factors, are stagnant. The steady increase in AIDS
      among women is linked to exposure to bisexual partners. The moderate nature of
      the national epidemic reflects, in part, the low incidence of IVDA, the universal
      screening of blood donors for antibodies to the human immunodeficiency virus
      (HIV) since 1985, and the prompt banning of unsafe coagulation factors. The
      projection of AIDS for the year 2000 is 2,304 cases (606 accumulated incidence
      per million inhabitants). A national educational campaign, radio and television
      programs and other preventive actions, apparently did not influence the rate of
      receptive anal intercourse without condom (about 80%) during 9 years of the
      epidemic. Persons with HIV/AIDS often are deprived of social and medical benefits
      or are subjected to harassment and exploitation by the health sector. More
      efficient prevention must target children, adolescents and adults in reproductive
      age, to promote safer lifestyles, through education and counseling effected
      through primary health care.

PMID- 8574147
TI  - Properties of virus-like particles produced by SIV-chronically infected human
      cell clones.
AB  - SIVsm chronically infected cultures were obtained after infection of CEMX174
      cells with either SIVsmH3 or SIVsmE660. These phenotypically CD4 cells, formed
      syncytia but only when cocultivated with CD4+ cells. Single cell clones were
      derived from these cultures and examined for the production of virus-specific
      proteins. The majority of the clones expressed SIV p27 antigen and low levels of
      virus reverse transcriptase activity. Western blot analysis, performed with
      either monoclonal or polyclonal sera, showed that a chronically infected clone
      (B7) produced particles which contained envelope (gp135 and gp43), gag precursors
      and gag proteins (p27, p16 and p8). However, these particles (SIVsmB7) lacked
      detectable levels of vpx and of integrase, and contained several fusion proteins
      which expressed viral protease antigens. This defective virus failed to infect
      established CD4+ cell lines, as well as primary cultures of macrophages and of
      peripheral blood lymphocytes, obtained both from humans and from rhesus macaques.
      Lack of infection correlated with lack of viral DNA detection by PCR
      amplification of genomic DNA extracted from these cell cultures. In addition,
      SIVsmB7 virus lacked infectivity in vivo. Rhesus macaques inoculated with high
      concentrations of SIVsmB7 showed no viremia and their PBMC were PCR negative.
      Thus, B7 cells produced stable, non-infectious virus mutants, which contained env
      and gag proteins, but lacked detectable amounts of vpx and of enzymes required
      for virus replication. Due to the high constitutive expression of this virus-like
      particle, we are now testing this preparation as a vaccine.

PMID- 8574149
TI  - Changes in serum antioxidant concentrations during infection with caprine
      lentivirus.
AB  - We are currently using caprine arthritis encephalitis virus (CAEV) infection in
      goats as a model to understand changes in some clinical parameters and host
      response to infection with human immunodeficiency virus (HIV). The objective of
      this study was to measure changes in serum antioxidant activities in various age
      groups of goats infected with CAEV. Serum from CAEV-infected goats had
      significantly higher catalase activity (105.47 +/- 5.96 kU/l) than serum from
      healthy control goats (79.92 +/- 17.06 kU/l). Moreover, serum catalase activity
      increased with increase in the time after infection with CAEV. No change was
      observed in total superoxide dismutase (SOD) or glutathione peroxidase activity
      although CuZn SOD levels were elevated in infected goats. There was a positive
      correlation between serum catalase activity and hydrogen peroxide (H2O2)
      scavenging activity (r = 0.70, p < 0.05). In order to investigate cell membrane
      integrity, we determined lactate dehydrogenase (LDH) activity in infected goats.
      Although there was a transient increase in LDH no correlation was observed
      between increased serum catalase activity and LDH activity (r = 0.16, p > 0.05).
      We have earlier observed decreased oxyradical production in CAEV infected goats.
      This observed increase in serum catalase, a scavenger of endogenous free radicals
      such as H2O2 may be partly responsible for the observed decrease in oxygen
      radicals found in vivo.

PMID- 8574150
TI  - A mutant approach and molecular strategy to study fungal cell walls.
AB  - The current study describes recombinant plasmids which complement the
      hypersusceptibility to killing bleomycin of blm1-1 mutant cells of Saccharomyces
      cerevisiae, and a strategy developed and used to recover active clones from a
      stable yeast genomic library. The resistance of a spontaneous revertant isolated
      from the original blm1-1 mutant strain and of mutant cells transformed with each
      of several recombinant plasmids which complemented the recessive blm1-1 mutation
      was comparable to the resistance of the parental (non-mutant) strain from which
      the original blm1-1 mutant was derived. The strategy for cloning S. cerevisiae
      DNA was based on complementation and in situ hybridization. This strategy
      employed 32P-labelled 6.6-kb BamHI and 3.8-kb BamHI-ClaI probes from a cloned DNA
      fragment to recover clones which either fully or partially complemented the
      hypersensitivity of mutant cells to killing by bleomycin. This method
      considerably reduced the time and effort required to recover biologically active
      clones from a genomic library.

PMID- 8574152
TI  - Synthesis, activity and toxicity of novel macrocyclic ligands against HIV-1 in
      Jurkat and CEM-SS cell lines.
AB  - We have developed versatile synthetic routes that afford metal-free macrocycles
      containing different functionalities in their framework. Novel oxaziridine and
      amide containing macrocycles were synthesized, and the metal complexes of the
      latter were also prepared. A series of theophilline and thymidine side-arm
      containing podands as well as macrocycles were obtained employing the same
      methodology. The primary anti-viral tests of these synthetic compounds for anti
      HIV-1 activity was carried out using the XTT-based cytopathicity assay (CEM-SS
      cells) with AZT as positive control. It was found that the nature of the
      macrocyclic headgroups affected the anti-HIV-1 activity. Heteroatom containing
      macrocyclic headgroups displayed activity in the micromolar range. Metal
      complexation did not enhance the activity and side-arm substitution resulted in
      inactive compounds. Cell viability determined in both Jurkat and CEM-SS cells was
      strongly dependent on the structure of the macrocyclic framework. The oxaziridine
      moieties in the macrocycle were highly toxic to CEM-SS and less toxic to Jurkat
      cell lines, while amide containing macrocycles were toxic to neither.

PMID- 8574151
TI  - Distribution of linear antigenic epitopes on GP120 encoded in sibling clones of
      novel New York HIV-1 subtype B isolates.
AB  - We have initiated studies to characterize the predominant subtypes of HIV-1 which
      account for infections in a defined cohort of intravenous (IV) drug addicts. A
      region of ENV encoding the C2 to the V5 regions was amplified from the leukocytes
      of two subjects currently enrolled in a methadone maintenance program at the
      Addiction Research and Treatment Corporation (ARTC), in Brooklyn, New York. This
      region of the viral genome encodes the principal neutralizing determinant (PND)
      located in the V3 loop, the immunogenic CD4-binding site, and six other linear
      antigenic epitopes in the envelope glycoprotein, gp120. Phylogenetic tree
      analysis of the nucleotide sequences showed that the sibling clones RT1.4,
      RT1.15, RT1.17, RT1.21 and RT3.6, RT3.10, RT3.11, RT3.12 and RT3.15 derived from
      the isolates, RT1 and RT3, respectively, cluster with "group B" viruses at 99%
      confidence level. Marked intra-patient and inter-patient sequence variation was
      apparent in the V3 loop. The divergence included the presence of a previously
      unreported hexapeptide GPWGTF at the cap of the loop in the clones from RT1. The
      North American consensus hexapeptide, GPGRAF, was identified in the cap of the
      loop from the clones of RT3. Four of the five sibling clones from RT3 were
      closely related whereas the other clone, RT3.15, displayed five amino acid
      mutations downstream of the V3 cap. To assess the effect of sequence variation on
      the distribution of linear antigenic epitopes, complementary computer software
      programs, were used to analyze the gp120 residues. Eight analogous antigenic
      epitopes were identified in the clones from both isolates despite the marked
      divergence in the primary sequences.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574153
TI  - Changes in viral expression and cytokine profile induced by a polyantigenic
      immunomodulator in HIV-infected peripheral blood mononuclear cells.
AB  - This is the first time, to our knowledge, that evidence is presented showing that
      a polyantigenic immunomodulator (PAI), acting as a biological response modifier,
      can either induce or suppress HIV expression depending on the viral load of
      infected PBMC. PAI consists of a mixture of inactivated bacteria with influenza
      virus vaccine. PBMC from HIV-infected patients (asymptomatic, age 22-36,
      symptomatic, age 30-59 and pediatric, < 2 years old) were co-cultured with PHA
      stimulated PBMC from uninfected individuals in medium containing IL-2 and PAI.
      Parallel co-cultures were carried out in a PAI-free medium. Cultures were fed
      with PHA-stimulated PBMC from uninfected donors on a weekly basis. HIV-p24 ag and
      cytokine profiles (IL-1 beta, IL-2, IL-4, IFN-gamma and TNF-alpha) were
      determined on supernatants on day 14. Peripheral blood samples from each patient
      were evaluated at the beginning of the experiment as to total CD3, total CD19,
      CD3/CD4, CD3/CD8, CD16/CD56, CD8/HLA-DR and CD8/CD38 markers through flow
      cytometry. PAI was able to induce viral expression (up to 11,881 pg/ml of p24
      antigen) in cultures showing a low (less than 16 pg/ml) or no viral titer. In
      contrast, in those cultures with high viral titer (10(2)-10(5) pg/ml), a
      substantial reduction on the titer was observed upon exposure to PAI. PAI was
      able to induce the production of IFN-gamma and TNF-alpha while that of IL-4 and
      IL-1 beta was reduced. The predominant cell type detected in the blood samples of
      the studied subjects were CD8+, CD8+/CD38+ or CD8+/HLA-DR+.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8574154
TI  - Frequent presence of latent Epstein-Barr virus infection in peripheral T cell
      lymphomas. A review.
AB  - Two-hundred and four cases of peripheral T cell lymphoma (PTCL) occurring in
      Europeans without any sign of HIV-infection were investigated for their
      association with an Epstein-Barr virus (EBV) infection. Polymerase chain reaction
      (PCR) was applied for EBV-DNA detection, in situ hybridisation (ISH) for the
      cellular localization of EBV-encoded small nuclear RNA (EBER) and immediate early
      gene expression (BHLF) and immunohistology (IH) for the detection of EBV-encoded
      latent membrane protein 1 (LMP1) and EBV nuclear antigen 2 (EBNA2) expression.
      PCR and EBER-ISH produced congruent results in almost all cases with amplifiable
      DNA, leading to the finding of an overall frequency of EBV presence in 87/204
      (42.6%) of the PTCL cases. Through EBER-ISH, the virus was identified to be
      exclusively present in small and blastic bystander lymphocytes in 29 cases,
      whilst an additional infection of neoplastic T cells was observed in the
      remaining 58 EBV-positive cases. The entity presenting with the most frequent EBV
      infection of tumour cells was that of angioimmunoblastic type PTCL, whilst the
      primary cutaneous PTCLs only seldom harbored the virus. Forty-eight of the EBV
      positive TCLs showed an infection of a small proportion (1-20%) of the tumour
      cell population, whilst another ten cases, belonging to the pleomorphic TCL
      (PMTCL) group, displayed an infection of several to almost all neoplastic T cells
      (20-100%). Additional lytic EBV-infected cells could be detected in four cases by
      BHLF-ISH. LMP1 expression was present in a small proportion of the neoplastic T
      cells in 24 of the 58 cases with tumour cell infection, whilst an EBNA2
      expression was detectable only in one case. Some non-malignant EBV-infected B
      immunoblasts and Hodgkin/Reed Sternberg-like cells also expressed LMP1 in several
      cases. Our data imply a role of EBV in the pathogenesis of only a few PMTCL cases
      with predominant tumour cell infection, whilst the pathogenic significance of an
      EBV infection in the other PTCLs remains unclear due to the usually partial
      infection of the neoplastic cell component.

PMID- 8574155
TI  - Evaluation of cell death in EBV-transformed lymphocytes using agarose gel
      electrophoresis, light microscopy and electron microscopy. II. Induction of non
      classic apoptosis ("para-apoptosis") by tritiated thymidine.
AB  - There is an extensive literature dating back to the late 1950's, on the damaging
      biological effects of radiolabeling DNA in vivo. Nonetheless, tritiated thymidine
      has often been used to label DNA in studies of programmed cell death (apoptosis).
      In the present study, we have investigated the effects of incorporation of
      tritiated thymidine into the DNA of an Epstein-Barr virus-transformed cell line
      (NC-37) in the absence of any other apoptosis-inducing agent. Cells were
      incubated in media containing 1-20 microCi/ml [methyl-3H]-thymidine ([3H]-TdR).
      At each concentration of tritiated thymidine used, cell proliferation ceased
      within 12 hours of incubation. The mode of cell death caused by tritiated
      thymidine incorporation was evaluated using DNA degradation patterns and cellular
      morphology. DNA degradation, in the absence of a "ladder" pattern, was shown by
      agarose gel electrophoresis. Electron microscopy was used as the "gold standard"
      to evaluate the specific morphologic type of cell death that accompanied the DNA
      degradation. Although some of the features of apoptosis were present, the cells
      lacked the early margination of the chromatin within an intact nucleus and
      surface blebbing leading to apoptotic body formation, two characteristic
      morphological features of apoptosis. We, therefore, coined the term "para
      apoptosis" to be more precise about the morphologic type of cell death. The
      percent of para-apoptotic cells was quantitated by light microscopy using whole
      mount preparations (cytospins). The morphologic criteria of chromatin
      condensation, nuclear fragmentation, increase in cell density and cytoplasmic
      vacuolization were used for the evaluation of para-apoptosis by light microscopy
      of cytospin preparations. In the absence of tritiated thymidine, < 2% of the
      cells became apoptotic/para-apoptotic after 43 hours of incubation. However, at
      all concentrations of tritiated thymidine used in the incubation medium (1-20
      microCi/ml), the number of para-apoptotic cells increased. In addition, we
      detected perturbations in the timing of the cell cycle of the surviving cells and
      an increase in the number of micronuclei after only one division cycle. The
      induction of para-apoptosis and micronuclei formation represent two distinct
      modes of cell death caused by tritiated thymidine incorporation. These studies
      emphasize the necessity for morphological examination in characterizing the
      induction of cell death in a new experimental system.

PMID- 8574156
TI  - In vivo radiosensitizing effects of recombinant interleukin 6 on radiation
      resistant BCL-1 B-lineage leukemia cells in a murine syngeneic bone marrow
      transplant model system.
AB  - The ability of total body irradiation (TBI) to eradicate clonogenic leukemia
      cells from B-lineage acute lymphoblastic leukemia patients prior to bone marrow
      transplantation (BMT) is greatly hampered by their inherent or acquired radiation
      resistance. The radiorefractory nature of these cells is believed to contribute
      to the high relapse rate subsequent to TBI and BMT in patients with B-lineage
      acute lymphoblastic leukemia (ALL). A method by which clonogenic leukemia cells
      could be radiosensitized in vivo could be clinically beneficial. In the present
      study, we used a highly radiation resistant subclone of the murine B-lineage
      leukemia cell line BCL-1 in a syngeneic BMT model to investigate if any of the B
      cell stimulatory cytokines interleukin 2, interleukin 4, interleukin 5, or
      interleukin 6 could have radiosensitizing effects. All untreated BALB/c mice (N =
      33) inoculated with 1 x 10(6) BCL-1 cells died of disseminated leukemia within 24
      days with a median survival of 13.3 days. TBI (700 cGy = LD100/30 for BALB/c
      mice) followed by syngeneic BMT (N = 70) extended the median survival to 23.6
      days (P < 0.001 by log-rank test). A single intraperitoneal bolus injection of
      100 ng, 500 ng, or 2500 ng recombinant murine interleukin 6(rmIL-6) 2-4 hours
      before TBI extended the median survival to 32.5 days, 31.0 days, and 30.5 days,
      respectively (P < 0.01 by log-rank test for all dose groups). The improved
      survival was not due to any direct anti-leukemic activity of rmIL-6 and all
      control BALB/c mice (N = 15) that received the same doses of rmIL-6 but did not
      undergo TBI and BMT died of BCL-1 leukemia within 28 days with a median survival
      of 13.6 days. In contrast to rmIL-6, recombinant murine interleukin 5 (rmIL-5)
      had minimal radiosensitizing effects.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574158
TI  - The role of alpha-interferon in essential thrombocythaemia, polycythaemia vera
      and myelofibrosis with myeloid metaplasia (MMM): a concise update.
AB  - Treatment of essential thrombocythaemia (ET), polycythaemia vera (PV), and
      myelofibrosis with myeloid metaplasia (MMM) patients is frequently a difficult
      issue. To date, there is no generally accepted treatment for these diseases which
      can reduce the risk of thromboembolism and/or haemorrhagic events, avoid any
      increase in the frequency of secondary myelofibrosis and terminal blast
      transformation and decrease the reticulin content in the bone marrow of MMM
      patients. The most frequently used myelosuppressive agent is hydroxyurea (HU),
      but widespread application has failed to demonstrate that is not leukaemogenic.
      In patients with MMM, conflicting results have been obtained following alpha-IFN
      treatment. Haematological responses have been seen in 50% of the patients.
      Usually the patients showing good responses had a hyperproliferative type of
      disease. In only one case was a reduction of reticulin content of the bone marrow
      observed. Thus, these findings do not indicate alpha-IFN as a first-line therapy.
      On the other hand, the results of several reports in ET and PV patients have
      shown a reduction in the abnormal proliferation of megakaryocytes and erythroid
      elements, following alpha-IFN treatment. A reduction in spleen size has also
      frequently been seen. Together with the improvement of haematological parameters,
      clinical symptoms have also responded positively. Long term control of these
      diseases can be obtained with a well-tolerated low dose of alpha-IFN. However, PV
      and ET are not usually characterized by cytogenetic abnormalities, making it very
      difficult to demonstrate the disappearance of clonal haemopoiesis following alpha
      IFN therapy, even if this does occasionally occur, as evident from the two
      cytogenetic convertions described in the literature. As compared to
      myelosuppressive drugs or phlebotomy, alpha-IFN thus represents an attractive new
      treatment, able to exert a fundamental influence on these diseases, presumably
      without any untoward leukaemogenic or gonadotoxic activity.

PMID- 8574157
TI  - Sporadic activation of Epstein-Barr virus in thyroid lymphoma.
AB  - The causal role of Epstein-Barr virus (EBV) in the development of B-cell
      lymphoma, especially in immunocompromised individuals, has been suggested. The
      purpose of the present study was to evaluate an association of EBV with thyroid
      lymphoma (TL) and chronic lymphocytic thyroiditis (CLTH) which is known to play
      an important role in the development of TL. Thirty cases with TL and 28 with CLTH
      were studied for presence or absence of EBV genome in the lesions using the
      polymerase chain reaction (PCR) and the in situ hybridization method. EBV genomes
      were detected by PCR in one and two cases with CLTH and TL, respectively.
      Subtyping of EBV genome was possible in one TL case showing B-type in EBNA-2
      coding region. In situ hybridization revealed positive signals in the nucleus of
      lymphoma cells, which also expressed latent membrane protein-1. The present
      findings indicate that activation of EBV in TL is not common.

PMID- 8574159
TI  - Analysis of MDR1 and MDR3 multidrug resistance gene expression and amplification
      in consecutive samples in patients with acute leukaemias.
AB  - White blood cells from a total of 19 patients diagnosed as having acute
      lymphoblastic (ALL) or acute myeloid (AML) leukaemia were analysed (36 samples)
      for amplification and expression of the mdr1 and mdr3 genes. Nine of the patients
      had samples analysed at presentation and at subsequent stages of the disease (24
      samples, including 4 at second relapse). Patients received standard MRC UK Trial
      remission-induction treatment protocols appropriate to disease and age. No
      amplification of either the mdr1 or mdr3 gene was found in any of the samples,
      and neither were mdr3 transcripts detected by dot-blot analysis using gene
      specific probes. Transcripts of the mdr1 gene were found in only 2 ALL samples
      (of 10). However, mdr1 transcripts were detected in all AML patients and there
      was a significant increase in the transcript levels in these patients who went on
      to first and second relapse, compared with levels measured at presentation (P <
      0.001). The results support the hypothesis that P-glycoprotein-mediated drug
      resistance may be a significant factor in tumour cell resistance to chemotherapy
      at relapse following initial induction-remission therapy for acute myeloid
      leukemia.

PMID- 8574161
TI  - Defect of stromal microenvironment in long term bone marrow cultures of patients
      with acute and chronic myelogenous leukemias.
AB  - Inhibition of normal hemopoiesis is a regular finding in acute (AML) and chronic
      (CML) myelogenous leukemias and functional abnormalities of the hemopoietic
      microenvironment may be involved in this regard. In order to evaluate this
      possibility we studied the formation of adherent stromal cell layers (ASCL) in
      long term bone marrow cultures (LTBMC) of 7 patients with CML and 7 patients with
      AML and examined the ability of these ASCLs to support hemopoiesis after
      irradiation and a second inoculation of bone marrow cells. The formation of ASCLs
      was significantly impaired in CML and AML. These CML patients and 3 AML patients
      did not form typical ASCLs and the cellularity of these layers was greatly
      reduced. Colony forming unit granulocyte-macrophage (CFU-GM) production from bone
      marrow cells seeded on normal irradiated ASCLs peaked at week 3 and then
      gradually decreased by week 8. In CML and AML cocultures CFU-GM numbers decreased
      rapidly to zero by weeks 4-6 and did not differ significantly from the control
      cultures which did not contain preestablished ASCLs beginning from week 3. It is
      suggested that there may be a functional microenvironmental defect in CML and AML
      that may play a role in the pathogenesis of inhibition of normal hemopoiesis in
      these diseases.

PMID- 8574160
TI  - A controlled trial of tranexamic acid therapy for the reduction of bleeding
      during treatment of acute myeloid leukemia.
AB  - In order to determine the efficacy of the antifibrinolytic agent tranexamic acid
      (TA) in reducing bleeding and platelet transfusions during the treatment of acute
      myeloid leukemia (AML), we conducted a randomized placebo-controlled double-blind
      study. Patients with AML undergoing induction or postremission consolidation
      chemotherapy were randomized into TA or placebo groups. Patients were not given
      platelet transfusions prophylactically but only when bleeding occurred. The
      severity of any bleeding event was scored. Thirty eight patients were randomized
      during induction. There were no significant differences between the two groups in
      the number of bleeding events and their severity or in the number of platelet
      transfusions given. Eighteen patients were studied during consolidation. In
      contrast, to the induction period, during consolidation there was a significantly
      less severe bleeding tendency in the TA group resulting in a lower platelet
      transfusion requirement [3.7 +/- 4.1 vs. 9.3 +/- 3.3 platelet units (p < .05)].
      TA was well tolerated and no side effects were seen and no specific
      thromboembolic events were noticed. We conclude that giving TA during the
      thrombocytopenic period of AML patients undergoing consolidation chemotherapy is
      beneficial and safely reduces platelet transfusions.

PMID- 8574162
TI  - Successful treatment of accelerated and blastic phase of chronic myeloid leukemia
      with high-dose interferon alpha and hydroxyurea: a novel approach.
AB  - Six patients with either acceleration or blast crisis of transformed chronic
      myeloid leukemia (CML) were treated with high-dose interferon alpha in
      combination with hydroxyurea. All patients responded to the treatment by reversal
      to stable chronic phase. Two of these patients responded repeatedly during their
      course of disease. Median time for return to chronic phase was 4 weeks. Adverse
      side-effects such as nausea, vomiting, hairloss, fever, prolonged cytopenia were
      not observed.

PMID- 8574163
TI  - VAD-cyclosporine therapy for VAD-resistant multiple myeloma.
AB  - Few effective treatments are available for patients with multiple myeloma that is
      resistant to vincristine-doxorubicin by continuous infusion with high dose
      dexamethasone (VAD). In order to modulate p-glycoprotein, the multidrug
      resistance gene product, we administered a VAD-cyclosporine combination to
      patients with confirmed resistance to VAD. Twenty-five patients with multiple
      myeloma resistant to VAD received cyclosporine 4 mg/kg infused over 2 hours
      followed by a continuous infusion of 10 mg/kg/24 hrs for a total of 108 hours.
      VAD was given concurrently as a continuous infusion of vincristine 0.3 mg and
      doxorubicin 9 mg/m2 daily for 4 days with oral dexamethasone 20 mg/m2/day for 4
      days beginning on days 1, 9 and 17. Clinical response and toxicity were
      correlated with MDR expression in plasma cells and the effects of cyclosporine on
      liver function. Six of 25 patients responded (24%; 95% CI 9-45%) with a median
      remission time of 7 months. Clinical response did not correlate with either the
      measured or the calculated MDR expression in plasma cells. Responses occurred
      more frequently in patients who developed high cyclosporine blood levels and
      paralytic ileus. The occasional benefit from VAD-cyclosporine for resistant
      multiple myeloma appeared to be due to a higher bioeffective dose of VAD rather
      than successful modulation of MDR.

PMID- 8574164
TI  - p53 mutations, c-myc and bcl-2 rearrangements in human non-Hodgkin's lymphoma
      cell lines.
AB  - Fourteen Non-Hodgkin's lymphoma cell lines were generated and assessed for the
      presence of structural p53, c-myc and bcl-2 gene changes. Single or multiple
      changes were observed in 11 of the lines. Alterations of the p53 gene were most
      frequent and documented for 10 lines by immunoprecipitation using the antibodies
      PAb 240 and PAb 1801, sequencing studies and Southern blot analysis. A detailed
      study was performed in one of the cell lines (OCI-Ly 4) for which material of the
      original tumor sample was available. Two point mutations identified by sequencing
      cDNA derived from the cell line were also present in the original tumor specimen.
      In contrast, DNA prepared from fibroblasts of the same patient did not show the
      mutations. Six of the 14 lines demonstrated c-myc rearrangements, while bcl-2
      changes were observed in 4. The presence of c-myc was associated with shorter
      survival of this group of patients with aggressive disease. None of the other
      changes present as single or composite alterations were correlated with clinical
      outcome measures.

PMID- 8574165
TI  - Early development of acute myelogenous leukemia following kidney transplantation:
      possible role of multiple serum cytokines.
AB  - We report a patient who at the time of kidney transplantation for polycystic
      kidney disease was found to have an enlarged inguinal lymph node which later
      demonstrated evidence of extra medullary granulopoiesis. During the first two
      weeks following kidney transplantation, a striking leukemoid pattern developed
      and 2 months after transplant the patient was diagnosed with acute myelogenous
      leukemia (AML). Retrospective analysis of peripheral blood cytokines over this
      time revealed elevated levels of GMCSF and gamma IFN at the time of peak
      peripheral blood WBC with subsequent peaks in IL-4, IL-6 and IL-2 as the
      peripheral blood WBC fell. A rise in levels of TNF alpha also preceded the
      peripheral blood WBC rise (although these concentrations were at or below those
      following uncomplicated kidney transplants). The clinical course of AML in this
      patient was marked by relentless relapse despite chemotherapy. The possibility of
      cytokine facilitated tumor growth is discussed.

PMID- 8574166
TI  - Fatal bone marrow necrosis following fludarabine administration in a patient with
      indolent lymphoma.
AB  - We report the first known case of fulminant bone marrow necrosis (BMN) occurring
      after infusion of fludarabine monophosphate in a patient with recurrent low-grade
      non-Hodgkin's lymphoma (NHL). Extensive BMN is characterized by the development
      of fever, bony pain, a leukoerythroblastic peripheral blood film, variable
      degrees of pancytopenia and elevations in lactate dehydrogenase and alkaline
      phosphatase. The diagnosis of BMN is rarely entertained ante-mortem. Although the
      precise role chemotherapy may have played in triggering fatal BMN remains
      speculative, we alert clinicians to be aware of this entity as more patients with
      indolent lymphomas and leukemias are treated with this and other potent
      nucleoside analogs.

PMID- 8574167
TI  - t(15;17) hypergranular acute promyelocytic leukemia (M3) developing into a t(3;6)
      M3 without t(15;17) at relapse.
AB  - This report describes a case of acute promyelocytic leukemia (APL) M3. At
      diagnosis, the specific t(15;17) translocation was observed. After chemotherapy
      including retinoic acid, a complete remission was achieved and the karyotype
      became normal. At relapse of the M3 leukemia, the t(15;17) clone was no longer
      observed but a t(3;6) translocation was then detected. Several hypotheses for
      this unusual cytogenetic course of APL are discussed.

PMID- 8574168
TI  - Impaired activation of phospholipase D in polycythaemia vera-implications for the
      pathogenesis of the disease?
AB  - A series of studies have demonstrated a stimulus-specific defect in PMN oxidative
      metabolism after stimulation with surface receptor dependent stimuli such as
      fMLP, leukotriene B4 and platelet activating factor (PAF), whereas the response
      to phorbol myristate acetate was normal. Having discovered this defect, studies
      of the stimulus response coupling for oxidative responses were performed showing
      a normal interaction of fMLP with it's receptor, as well as an intact activation
      of phospholipase C, as measured by the generation of 1,4,5-inositoltrisphosphate,
      and the subsequent rise of intracellular calcium. In contrast, the formation of
      diacylglycerol and phosphatidylethanol was decreased in PV PMN, denoting an
      impaired activation of phospholipase D (PLD). It was shown by flow cytometry
      analyses that the hampered oxidative response was present both in single PMN and
      monocytes. Moreover, platelets from PV patients, whose PMN exhibit a lower
      oxidative response to PAF, also have a diminished aggregatory response to PAF.
      Thus three different cell lineages in PV have been revealed to respond abnormally
      to surface receptor dependent stimuli, indicating that the proposed impairment of
      PLD might be relevant for changes in the malignant stem cell clone. Since
      phosphatidic acid, produced as a result of PLD activation, may be implicated in
      the regulation of several oncogenes, perturbations of the PLD system could
      theoretically be important for the development of PV.

PMID- 8574169
TI  - Transplantation-related complications predicted by cytokine gene expression in
      the mixed lymphocyte culture in allogeneic bone marrow transplants.
AB  - In this study, we have investigated cytokine (IL-1 beta, IL-2, IL-5, IL-6, IFN
      gamma, TNF-alpha) and T cell surface molecule (IL-2 receptor, CD28, CTLA-4) gene
      expression in two way mixed lymphocyte cultures (MLC) enhanced by concanavalin A
      (ConA) to assess whether this is a useful predictive method for severe graft
      versus-host disease (GVHD) and graft failure in allogeneic bone marrow
      transplantation (allo BMT) patients. Our present study revealed increased mRNA
      expression of IL-2, IL-5 and IFN-gamma using this assay in patients with delayed
      engraftment followed by graft failure and patients who developed grade III acute
      GVHD. Elevated IL-2 and IFN-gamma levels in MLC medium were also observed in
      these patients. Concerning T cell surface molecule gene expression in our
      modified MLC, IL-2 receptor gene expression was not altered so much in allo BMT
      patients, however, CD28 and CTLA-4 gene expression were elevated in patients with
      graft failure and severe acute GVHD. The elevated expression of cytokines (IL-2,
      IL-5 and IFN-gamma) and T cell surface molecules (CD28 and CTLA-4) mRNA in our
      modified MLC, in patients who developed severe lethal transplantation-related
      complications may suggest an important role for these molecules in inducing a
      strong alloresponse. Therefore, the detection of increased gene expression of
      those molecules, in our modified MLC system, appeared to be useful for predicting
      transplantation-related complications in allo BMT patients. In addition, this
      modified MLC assay may also be useful for the selection of the most compatible
      related and unrelated donors.

PMID- 8574170
TI  - Inhibition of GM-CSF production by recombinant human interleukin-4: negative
      regulator of hematopoiesis.
AB  - Interleukin-4 (IL-4), also known as B-cell stimulatory factor-1 (BSF-1), was
      initially identified as a T-cell product that mediates anti-IgM-induced DNA
      synthesis in B-lymphocytes. Various aspects of this highly pleiotropic cytokine
      have been described, including those on hematopoietic progenitor cells. However,
      the role of IL-4 in the hematopoietic system has been given different
      interpretations. Normal human hematopoietic progenitor cells do not proliferate
      under control of the autocrine system and cytokines are needed for proliferation
      and differentiation. However, IL-4 in itself does not support proliferation of
      these cells and if this is the case, the effects of IL-4 on hematopoietic
      progenitor cells still need to be investigated from the point of view of
      synergism with other cytokines as well as the control of accessory cells in the
      production of cytokines. We describe here some properties of IL-4 in association
      with cytokine production, with special emphasis on granulocyte-macrophage colony
      stimulating factor (GM-CSF) production.

PMID- 8574171
TI  - Apoptosis overview emphasizing the role of oxidative stress, DNA damage and
      signal-transduction pathways.
AB  - Apoptosis (programmed cell death) is a central protective response to excess
      oxidative damage (especially DNA damage), and is also essential to embryogenesis,
      morphogenesis and normal immune function. An understanding of the cellular events
      leading to apoptosis is important for the design of new chemotherapeutic agents
      directed against the types of leukemias and lymphomas that are resistant to
      currently used chemotherapeutic protocols. We present here a review of the
      characteristic features of apoptosis, the cell types and situations in which it
      occurs, the types of oxidative stress that induce apoptosis, the signal
      transduction pathways that either induce or prevent apoptosis, the biologic
      significance of apoptosis, the role of apoptosis in cancer, and an evaluation of
      the methodologies used to identify apoptotic cells. Two accompanying articles,
      demonstrating classic apoptosis and non-classic apoptosis in the same Epstein
      Barr virus-transformed lymphoid cell line, are used to illustrate the value of
      employing multiple criteria to determine the type of cell death occurring in a
      given experimental system. Aspects of apoptosis and programmed cell death that
      are not covered in this review include histochemistry, details of cell deletion
      processes in the sculpting of tissues and organs in embryogenesis and
      morphogenesis, and the specific pathways leading to apoptosis in specific cell
      types. The readers should refer to the excellent books and reviews on the
      morphology, biochemistry and molecular biology of apoptosis already published on
      these topics. Emphasis is placed, in this review, on a proposed common pathway of
      apoptosis that may be relevant to all cell types.

PMID- 8574172
TI  - Evaluation of cell death in EBV-transformed lymphocytes using agarose gel
      electrophoresis, light microscopy and electron microscopy. I. Induction of
      classic apoptosis by the bile salt, sodium deoxycholate.
AB  - In this study, we examined the effect of different concentrations of sodium
      deoxycholate (NaDOC), a secondary bile salt, on an Epstein-Barr virus transformed
      human lymphoid cell line (NC-37). We found that NaDOC induces classic apoptosis
      in a dose-dependent manner at 0.1-0.4 mM doses, and necrosis at much higher
      concentrations (0.8-3.1 mM). This is the first demonstration that a bile salt can
      induce apoptosis in any cell type. The mode of cell death was determined using
      morphologic methods (light and electron microscopy) as the gold standard.
      Standard agarose gel electrophoretic techniques were applied to identify the
      "ladder" of DNA fragments that have been associated with apoptosis in certain
      cell types. Although DNA fragmentation was observed during the apoptotic death of
      NC-37 cells, we were not able to identify a "ladder" pattern of fragmentation.
      Two other types of cells, however, that previously have been reported to display
      a characteristic "ladder" pattern of DNA fragmentation, glucocorticoid-treated
      WEHI7.2 cells and isolated human neutrophils, did display the "ladder" pattern.
      This study emphasizes the need to examine morphology when identifying the mode of
      cell death induced by a new agent.

PMID- 8574173
TI  - The role of the neurohormone melatonin as a buffer against macromolecular
      oxidative damage.
AB  - This paper summarizes the recent findings which show that the neural hormone
      melatonin is a free radical scavenger and general antioxidant. When compared with
      other antioxidants melatonin seems to have greater efficacy in protecting against
      cellular oxidative stress. These findings illustrate that melatonin preserves
      macromolecules including DNA, protein and lipid from oxidative damage following
      the administration of the chemical carcinogen, safrole, after exposure to
      ionizing radiation, following glutathione depletion, and after administration of
      the free radical generating herbicide, paraquat. In vitro evidence shows that
      melatonin is a potent scavenger of the highly toxic hydroxyl radical and in vitro
      evidence suggests that melatonin is an important and powerful antioxidant.
      Considering its high lipophilicity and its non-toxic nature as well as its
      ability to readily cross the blood-brain barrier, the neurohormone melatonin may
      prove to be an effective and important molecule in the antioxidative defense
      system, especially in the central nervous system. Besides the ease with which
      melatonin enters the brain, neurons seem to accumulate readily this hormone.

PMID- 8574174
TI  - Profile of prostaglandin levels in the rat hippocampus in pilocarpine model of
      epilepsy.
AB  - Pilocarpine (PILO) administered to rats acutely induces status epilepticus (acute
      period), which is followed by a transient seizure-free period (silent period),
      and finally by a chronic phase of spontaneous recurrent seizures (chronic period,
      SRS) that lasts for the rest of animal's life. Hippocampal neurochemical changes
      following PILO administration include alteration in monoamines and amino acids
      content during all phases of this epilepsy model. The present work was delineated
      to study the content of prostaglandins (PG) levels in hippocampus during the
      three phases of this model. The levels of PG E2, PG F2 alpha and PG D2 were
      measured by radioimmunoassay 1 h after PILO, 5 h after PILO, during the silent
      period, and interictally into the chronic period. The results show, in
      hippocampus of rats, increase of PG F2 alpha and PG D2 during status epilepticus,
      increase of PG D2 during the silent period and increase of PG E2 and PG D2 during
      the chronic phase, when compared with control group. These changes match
      previously reported alteration in monoamines and amino acid levels, showing that
      altered neurotransmission is accompanied by changes in second messengers and
      enzyme activity related to PG production during all phases of the epilepsy model.

PMID- 8574175
TI  - The imbalance of brain large-chain aminoacid availability in amyotrophic lateral
      sclerosis patients treated with high doses of branched-chain aminoacids.
AB  - Following the report of an increased mortality among patients with amyotrophic
      lateral sclerosis given high daily doses of branched-chain aminoacids, we
      assessed the plasma concentrations of large neutral aminoacids and glutamic acid
      and the large neutral aminoacid brain influx in 24 amyotrophic lateral sclerosis
      patients receiving placebo or branched-chain aminoacids (L-leucine 12 g, L
      isoleucine 6 g, L-valine 6 g daily), in 15 untreated amyotrophic lateral
      sclerosis patients and in 15 healthy volunteers. The branched-chain aminoacid
      plasma concentrations increased three- to six-fold in the treated group compared
      to the patients receiving placebo or no treatment and to the healthy controls.
      Plasma glutamic acid concentrations in healthy volunteers were 51.59 +/- 7.53
      nmol/ml while in the amyotrophic lateral sclerosis patients receiving no
      treatment, placebo or branched-chain aminoacids were 92.33 +/- 12.15 nmol/ml,
      91.21 +/- 15.86 nmol/ml and 95.08 +/- 17.96 nmol/ml respectively. The glutamic
      acid concentration was significantly higher (P < 0.01) in amyotrophic lateral
      sclerosis patients than in healthy individuals. Plasma phenylalanine and tyrosine
      were lower in the amyotrophic lateral sclerosis patients than in healthy
      controls, regardless of treatment, whereas tryptophan levels were not
      significantly different. The branched-chain aminoacid brain influx of the treated
      group was 110-140% of that measured in the patients receiving placebo and in the
      healthy controls. The aromatic aminoacid brain influx was lower in the treated
      group than in the placebo group or healthy controls. An impairment of brain large
      neutral aminoacid availability might possible contribute to enhancing the
      progression of symptoms in patients with amyotrophic lateral sclerosis.

PMID- 8574176
TI  - Signal transmission in the photosensitive pineal organ of the rainbow trout:
      modulation of ganglion cell activity by intrinsic dopamine.
AB  - The photosensitive pineal organ of the rainbow trout (Oncorhynchus mykiss)
      transduces photic information into nycthemeral neuronal signals. To investigate
      origin, cellular localization, and functional significance of pineal
      catecholamines, we performed HPLC-analysis of catecholamines and tyrosine
      hydroxylase (TH) activity, as well as immunocytochemical and electrophysiological
      studies. In biochemical and immunocytochemical investigations, pineal cells were
      found to contain endogenous TH. Using HPLC-analysis, the presence of a
      catecholamine precursor (L-dopa), catecholamines (dopamine, norepinephrine,
      epinephrine), and a metabolite (DOPAC) was demonstrated. The release of L-dopa,
      dopamine and DOPAC from isolated pineal organs was shown by superfusion
      experiments. Extracellular recordings were used to monitor the action of
      dopaminergic drugs on electrical activity of ganglion cells. Dopamine increased
      the discharge activity of action potentials, whereas dopamine receptor
      antagonists resulted in a reduction of ganglion cell activity. Our data provide
      evidence for establishing dopamine as an intrinsic neurotransmitter or
      neuromodulator in the photosensitive pineal organ of the rainbow trout.

PMID- 8574177
TI  - Diminution of preprosomatostatin-mRNA in cerebral cortex of the aged rat.
AB  - The aim of the present study was to examine the effect of normal aging on
      somatostatin neurotransmission. Somatostatin gene expression was analysed in
      several regions of the cerebral cortex and hippocampus in 3, 7 and 21 month-old
      Sprague-Dawley rats using quantitative in situ hybridization with a 48mer
      oligodeoxynucleotide antisense probe. Furthermore the distribution of 125I-Tyr11
      somatostatin receptor binding sites was studied using quantitative receptor
      autoradiography. The results demonstrated a significant reduction of
      preprosomatostatin-mRNA in the frontal cortex of the aged (21 month) group
      compared with the young (3 month) and the middle-aged (7 month) groups. The
      receptor binding densities of the aged (21 month) group tended to be lower,
      compared to the other groups although no significant region-specific changes were
      evident. These results indicate neurochemical changes in somatostatin-containing
      neurons in the frontal cortex during aging.

PMID- 8574178
TI  - Influence of lipid peroxidation on [3H]ketanserin binding to 5-HT2 prefrontal
      cortex receptors.
AB  - The influence of lipid peroxidation on 5-HT2 receptor binding was examined in
      prefrontal cortex membranes from sheep brain. Lipid peroxidation was induced with
      ascorbic acid and ferrous sulphate and measured by the thiobarbituric acid
      method. In lipid-peroxidized membranes, [3H]ketanserin specific binding was
      inhibited. The Bmax values decreased by 80%, from 50.1 +/- 3.5 fmol/mg protein in
      control membranes to 10.1 +/- 2.0 fmol/mg protein in peroxidized membranes,
      indicating a decrease in the number of 5-HT2 binding sites. However, the KD
      values for the [3H]ketanserin specific binding did not significantly change. In
      order to further characterize [3H]ketanserin binding, the inhibition potency
      (IC50 values) of antagonists or agonists of serotonin and dopamine receptors for
      [3H]ketanserin specific binding was determined. In control membranes, the order
      of inhibition potency of the drugs tested was the following: ketanserin (
      log[IC50]=8.56 +/- 0.70] > ritanserin (-log [IC50]=8.13 +/- 0.30)>methysergide (
      log[IC50]= 7.42 +/- 0.50)> spiperone (-log[IC50]=7.23 +/- 0.18 > serotonin (-log
      [IC50] = 6.99 +/- 0.65)> haloperidol (-log[IC50]= 6.95 +/- 0.65) > dopamine (-log
      [IC50] = 5.82 +/- 0.76). After membrane lipid peroxidation, the IC50 value for
      ritanserin was significantly increased, suggesting a decreased capacity for
      displacing [3H]ketanserin specific binding. Other antagonists of 5-HT2 receptors
      showed apparent increases in IC50 values upon peroxidation, whereas spiperone was
      shown to be the most potent drug (-log[IC50]= 7.19 +/- 1.06) in inhibiting
      [3H]ketanserin specific binding. A decrease in polyunsaturated fatty acids,
      namely docosahexaenoic acid (22:6) was also observed in peroxidized membranes.
      These results indicate a modulating role of the surrounding lipids and of the
      physical properties of the membranes on the binding activity of 5-HT2 receptors
      upon the lipid peroxidation process, which can be involved in the tissue
      impairment that occurs during the aging process and in post-ischemic situations.

PMID- 8574179
TI  - Localization of dopamine D1-receptors in vertebrate retinae.
AB  - We used the fluorescent labelled dopamine D1-receptor antagonist Bodipy-SCH 23390
      for the cellular localization of D1-ligand binding sites in the retinae of
      different vertebrates (teleosts, Xenopus, turtle, rat and rabbit). Competition
      experiments with unfixed cryosections of fish retina were performed to
      characterize the binding conditions of Bodipy-labelled SCH 23390. Tissue bound
      [3H]SCH 23390 was displaceable with increased amounts of bodipy-SCH 23390. The
      pharmacological specificity of the D1 fluorescent antagonist was determined by
      competition experiments with an excess of unlabelled SCH 23390. This treatment
      significantly reduced the level of fluorescence of the retina confirming the
      specificity of the binding. We observed a homogeneously distributed fluorescence
      signal in both plexiform layers in unfixed cryosections of fish, frog, turtle,
      rat and rabbit. Similar staining intensities of both plexiform layers were found
      in frog, turtle, rat and rabbit retina. In teleosts, the label of the outer
      plexiform layer was markedly more intense. Non-specific label was associated with
      photoreceptor outer and inner segments. The specific labelling of both plexiform
      layers indicates a mismatch of dopamine releasing and D1-binding sites, and
      suggests a possible extrasynaptic localization of the D1-receptor. The
      physiological significance of the observed distribution of D1-ligand binding
      sites is discussed with respect to the role of dopamine in controlling
      adaptational processes in the retina.

PMID- 8574180
TI  - Immunocytochemical demonstration of taurine in the retina and pineal organ of the
      pigeon.
AB  - Taurine-like immunoreactivity (TLI) is found in the pigeon retina at high levels
      within cones, in select cells of the inner nuclear layer and in sublaminae of the
      inner plexiform layer. At the ultrastructural level a high density of immuno-gold
      particles in visualized in the ellipsoid, but not in the paraboloid area of the
      inner segment. It is present in perikarya and the presynaptic endings of cones,
      but not in postsynaptic cell processes. The immuno-gold particles are not
      associated directly with the synaptic vesicles. In the pineal organ TLI was
      confined to the so-called dark pinealocytes which are surrounded by only family
      stained light pinealocytes. Clusters of protein A-gold particles are located in
      the ergastoplasm between polyribosomes adjacent to fibrous proteins and in chains
      along filamentous structures. Granules, vesicles and membrane whorls, which
      originate from modified cilia remain unlabeled. The results are discussed on the
      basis of previous findings; a direct or indirect functional relationship of
      taurine to ATP-dependent processes is suggested.

PMID- 8574181
TI  - Does histamine stimulate cyclic AMP formation in the avian pineal gland via a
      novel (non-H1, non-H2, non-H3) histamine receptor subtype.
AB  - The effects of histamine (HA) and selective HA H1-, H2 and H3-receptor agonists
      on cyclic AMP formation were investigated in intact chick and duck pineal glands
      HA potently stimulated the pineal cycle AMP formation. The effect of HA was
      mimicked fully by N alpha-methylated histamines, and partially by several
      histaminergic drugs: 2-thiazolylethylamine (H1) amthamine (H2) and R alpha-methyl
      histamine (H3). Dimaprit, another selective H2-agonist showed marginal activity.
      Forskolin highly potentiated the action of HA, and only weakly affected the
      effects of 2-thiazolylethylamine and amthamine. In the chick pineal, the
      stimulatory effects of HA and the tested histaminergic drugs were not blocked by
      mepyramine and thioperamide (H1- and H3-blockers, respectively), but they were
      antagonized by H2-receptor selective compounds ranitidine and aminopotentidine,
      which, however, acted in a noncompetitive manner. Another H2-selective blocker
      zolantidine antagonized the HA effect only when used at very high (30-100 microM)
      concentrations. In the duck pineal, the stimulatory effect of HA on cyclic AMP
      production was unaffected by mepyramine (H1), thioperamide (H3), and ranitidine
      (H2), and only partially inhibited by the H2-blocker aminopotentidine.
      Electrophysiological experiments revealed that HA is capable of evoking inward
      currents in most of the tested cells acutely isolated from chick pineal gland.
      The present findings further indicate that the pharmacological profile of the
      avian pineal HA receptor, whose stimulation leads to activation of cyclic AMP
      production, is different from any known HA receptor type (H1, H2, H3), and
      suggest the existence of either an avian-specific HA receptor, or a novel HA
      receptor subtype. Electrophysiological data suggest that the pineal HA receptor
      may be somehow linked to activation of an ionic channel.

PMID- 8574182
TI  - Effects of phosphodiesterase inhibitors and forskolin on cyclic GMP-activated
      channels in intact isolated cells of the chick pineal gland.
AB  - Application of the phosphodiesterase inhibitors isobutylmethylxanthine (100
      microM) caused activation of a low-conductance cationic channels in intact acute
      isolated chick pineal cells. This effect required continued contact between the
      cytoplasmic face of the patch membrane and the cytoplasm. The biophysical
      properties of the channels were identical to those of cyclic GMP-activated
      channels described previously on excised patches. Application of 40 microM
      forskolin did not cause activation of the low-conductance channels. A second
      population of spontaneously active large-conductance cationic channels was
      observed in some patches. Gating of large-conductance channels was not affected
      by phosphodiesterase inhibitors of forskolin. These results support the theory
      that phototransduction cascades similar to those of the vertebrate retina are
      also present in chick pineal cells.

PMID- 8574183
TI  - Dopamine-dependent cyclic AMP generating system in chick retina and its relation
      to melatonin biosynthesis.
AB  - Stimulation of a D4-like dopamine (DA) receptors inhibits a cAMP-dependent
      increase in serotonin N-acetyltransferase activity and melatonin biosynthesis in
      the chick retina. In order to gain more insight into the molecular mechanisms
      underlying this suppressive action of DA, the effects of selective stimulation of
      the D2-family of DA receptors (including the D4-subtype) on cAMP formation were
      examined in chick retina using two experimental approaches: measurements of
      adenylyl cyclase activity in retinal homogenates, and cAMP accumulation in eye
      cup preparation prelabeled with [3H]adenine. The DA-sensitive adenylyl cyclase
      system is well expressed in chick retina. DA increased both basal and forskolin
      stimulated adenylyl cyclase activity. This effect of DA was antagonized by SCH
      23390 (a blocker of D1-family of DA receptors) and not affected by sulpiride (a
      D20-family blocker). Incubation of retinal homogenates with quinpirole (a
      predominant agonist of D3/D4 DA receptor subtypes) did not produce any major
      changes in adenylyl cyclase activity. On the other hand, activation of D4-like DA
      receptor subtype by quinpirole decreased forskolin-stimulated cAMP formation in
      intact chick retina maintained in "eye-cup" preparations. It is suggested that D4
      like DA receptors regulating melatonin biosynthesis in chick retina may be
      indirectly linked to the cAMP generating system.

PMID- 8574185
TI  - Construction of subtractive cDNA library using magnetic beads and PCR.

PMID- 8574184
TI  - In situ PCR: protocols and applications.
AB  - Many groups have now published data based on the in situ detection of PCR
      amplified DNA and cDNA. As with standard in situ hybridization or PCR, variables
      that can affect in situ PCR results include type of fixative and time of
      fixation, protease digestion, and the composition of the amplifying solution and
      oligoprobe cocktail. Investigators new to the field of in situ PCR should first
      try direct incorporation of the reporter molecule into paraffin-embedded tissue
      sections. Although nonspecific DNA synthesis is generated under these conditions,
      one can develop the confidence of synthesizing DNA inside the nucleus and
      appreciate the importance of protease digestion time to successful RT in situ
      PCR. It is an arguable statement that the in situ detection of PCR-amplified DNA
      and cDNA will have a very strong impact on many diverse fields, such as
      oncogenesis, embryology, RNA trafficking, and detection of viral diseases, as it
      already has on our understanding of the pathogenesis of HIV-1 infection.

PMID- 8574186
TI  - The one-tube quantitative HIV-1 RNA NASBA: precision, accuracy, and application.

PMID- 8574187
TI  - Advances in PCR-based detection of mycoplasmas contaminating cell cultures.

PMID- 8574189
TI  - Background-minimized cassette mutagenesis by PCR using cassette-specific
      selection markers: a useful general approach for studying structure-function
      relationships of multisubstrate enzymes.
AB  - An efficient protocol, termed background-minimized cassette mutagenesis (BMCM) by
      PCR, has been developed for multiple mutagenesis of DNA. This method uses
      suitable extension primers for incorporating various mutation(s) and is not
      limited by either the nature of the mutation or the size and spatial location of
      mutational loci. Minimization of the wild type background clone and mutant
      selection at very high frequency were easily achieved through a two-step process.
      First, a deletion of a unique restriction site within the cassette was introduced
      through additional silent mutation(s). Then, the recombinant clones were digested
      with the corresponding enzyme followed by transformation when selective
      linearization of wild-type clone led to its near total removal leaving the mutant
      clones as the only practicable transformants. Because it is generally possible to
      design several such cassette-specific unique background minimization markers for
      any gene, for multiple mutagenesis involving distally located portions of the
      gene the present protocol is superior to other currently available methods. The
      efficiency of BMCM-PCR has been demonstrated here by using the multisubstrate
      enzyme 5-enolpyruvyl-shikimate-3-phosphate synthase (EPSPs) of Bacillus subtilis
      as a model system. Three different sets of cassettes of varying sizes were
      generated to encompass the three putative active/binding regions in the
      beginning, middle, and the end of the gene encoding EPSPs. Very high efficiency
      of mutation incorporation and selection were obtained in all cases. Furthermore,
      by taking advantage of the unique cassette-specific background elimination
      markers, it was possible to generate a nested set of double and/or triple
      mutants. The mutant enzymes were overexpressed in Escherichia coli and purified
      to near homogeneity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574188
TI  - Catch-linker + PCR labeling: a simple method to generate fluorescence in situ
      hybridization probes from yeast artificial chromosomes.
AB  - A simple and efficient method to generate hapten-labeled DNA fragments from a
      trace amount of YAC DNA isolated by PFGE is described. After agarase digestion of
      the gel slice containing the resolved YAC recombinant, the purified DNA is
      digested with Sau3Al and a compatible CL oligonucleotide duplex ligated on. A
      probe is generated by PCR amplification using a primer complementary to the CL
      with a single biotin moiety incorporated at the 5' end. When used as a FISH
      probe, this material yields mapping results superior to Alu-PCR or whole YAC
      labeling methods and allows sensitive detection of chimerism.

PMID- 8574190
TI  - An evaluation of competitor type and size for use in the determination of mRNA by
      competitive PCR.
AB  - The technique of competitive PCR for measuring mRNA is used widely. Several
      variations of the method have been reported. We have evaluated some of the
      commonly used competitor types as part of our study into expression of the
      androgen receptor (AR). These included mutant, intron, deletion construct, and
      nonhomologous competitors, which were assessed with an emphasis on their ability
      to amplify the target with the same efficiency, as well as their capacity to form
      heteroduplexes with it. The effect of competitor size on amplification efficiency
      was also investigated. We found that the use of a common primer set did not
      guarantee equal amplification efficiencies among DNAs sharing the same primer
      sequences. For the competitors evaluated in this study, sequence length was the
      major determinant of amplification efficiency. The longest competitors were
      amplified with the least efficiency. Differences in amplification efficiencies
      were corrected for by standardizing the competitor against the target.
      Constructing competitors of different sizes to the target may not eliminate
      heteroduplex formation when they share common sequence with the target as with
      the intron and deletion type competitors. Such heteroduplexes may interfere with
      the analysis if they cannot be resolved from both the target and competitor. Use
      of a mutant competitor constructed by the conversion of one enzyme restriction
      site to another produced determinations that were independent of both
      heteroduplex formation and cycle number. A method is described for generating a
      mutant competitor with a single PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574191
TI  - Metastable single-strand DNA conformational polymorphism analysis results in
      enhanced polymorphism detection.
AB  - Single-strand DNA conformational polymorphism (SSCP) makes use of sequence
      dependent folding of single-stranded DNA (ssDNA), which alters the
      electrophoretic mobility of the fragments, to detect sequence differences between
      closely related molecules. In this study ssDNAs were purified by depletion of the
      complementary strand and PCR reactants on magnetic M-280-strepavidin beads. It
      was found that SSCP profiles created by purified ssDNAs differ from the profiles
      created by more usual SSCP methods. Under some conditions, SSCP profiles using
      whole PCR reaction products may result from the interaction between residual PCR
      primers and ssDNAs. We observed that the ratio of conformers revealed by band
      position and band intensity may vary between the assay techniques and
      misinterpretation of sequence variants may result. Another observation of this
      study was the formation of metastable conformational isomers with bead-purified
      ssDNAs by eliminating the thermal treatment used in conventional SSCP methods.
      The metastable SSCP (mSSCP) represents a novel and sensitive system for detection
      of sequence variation between closely related DNAs. The technique used here for
      the preparation of the purified ssDNAs is potentially useful for automated PCR
      SSCP analysis using capillary electrophoresis or other methods.

PMID- 8574192
TI  - Quantitative detection of reverse transcriptase-PCR products by means of a novel
      and sensitive DNA stain.
AB  - We constructed a plasmid for the in vitro synthesis of a competitor RNA for use
      as an internal exogenous control during reverse transcriptase--PCR (RT-PCR)
      detection of epidermal growth factor receptor (EGFR) expression. The competitor
      RNA harbors a 32-base deletion compared with wild-type EGFR mRNA and generates a
      PCR product that is easily distinguished from the wild-type PCR product by
      agarose gel electrophoresis. We encountered the problem of heteroduplex formation
      during later stages of PCR, which could be solved by decreasing the PCR cycle
      number. This was accompanied by a significant loss of sensitivity. Sensitivity
      could be restored by using a novel and extremely sensitive DNA stain (SYBR Green
      I) instead of ethidium bromide.

PMID- 8574194
TI  - Identification of the species origin of highly processed meat products by
      mitochondrial DNA sequences.

PMID- 8574193
TI  - PCR with deoxyinosine-containing primers using DNA polymerases with proofreading
      activity.

PMID- 8574195
TI  - Cellular interactions during heart morphogenesis in the Drosophila embryo.
AB  - The formation of the dorsal vessel or heart in a Drosophila melanogaster embryo
      can be divided into three main steps: i) the determination step allows
      individualization of heart precursor cells from the dorsal mesoderm. They are
      arranged in clusters of seven to nine cells, located in each of the eleven
      segments of the trunk. Preliminary observations suggest that the gene Notch could
      participate in the choice of fate that the cardioblasts and the pericardial cells
      will adopt within the cardiogenic region. In the same line, a new gene, whose
      expression, as revealed by a P-lacZ insertion, is initiated at gastrulation in
      the developing mesoderm and becomes restricted within the mesoderm to the
      myogenic lineages, could participate in the determination of the cardioblasts
      identity; ii) once the cardioblasts have separated from the dorsal mesoderm, they
      reorganize to form an epithelial monolayer. The gene coding for the alpha-subunit
      of the transduction protein Go, which is expressed in the cardioblasts shortly
      before this step, could be involved in this process. Indeed, mutants in the Go
      alpha gene are affected in the formation of the cardiac endothelium; and iii) the
      last step consists of the migration of the cardiac epithelium towards the dorsal
      midline of the embryo to form the dorsal vessel by apposition of the two layers
      of cardioblasts. We show that an extracellular matrix component is specifically
      expressed at the surface of the dorsal vessel and could participate in the
      interaction between the dorsalmost ectodermal cells and the heart during this
      migration step.

PMID- 8574196
TI  - Analysis of the role of basic-helix-loop-helix transcription factors in the
      development of neural lineages in the mouse.
AB  - The development of neural lineages is a complex process which is being actively
      investigated in both vertebrate and invertebrate models. A detailed genetic
      analysis of sensory organ development in Drosophila has revealed the contribution
      of numerous genes which function to progressively to specify the fate of neural
      precursor cells. Many of these genes have mammalian homologs which are also
      expressed in the developing nervous system, among which two families of genes
      encoding transcription factors of the helix-loop-helix class. The two mouse Mash
      genes are homologs of the Drosophila achaete-scute genes, which are positive
      regulators of neural precursor development. The five mouse HES genes are homologs
      of the Drosophila hairy and Enhancer of split genes, which act as negative
      regulators in this process. We have generated a null mutation in the mouse Mash1
      gene by homologous recombination in embryonic stem cells. Animals homozygous for
      this mutation die at birth, and show severe losses in olfactory and autonomic
      neurons. In both lineages, the mutation appears to affect the development of
      neuronal precursors. We have also started a genetic analysis of the mouse HES
      genes to study their function during neurogenesis and the possibility that they
      regulate the activity of Mash1 and other positive regulators.

PMID- 8574197
TI  - Regulation of the P25 gene transcription in the silk gland of Bombyx.
AB  - The gene encoding the silk protein P25 is specifically transcribed in the
      posterior silkgland of Bombyx during larval intermoults and is repressed during
      moults. By performing in vitro DNA-protein interactions, at least five putative
      regulatory elements were localized in the 5' flanking region of the gene. The
      most proximal element, close to the TATA box, interacts with SGFB, a silkgland
      specific factor which could be involved in the tissue-specific expression of the
      gene. A more upstream sequence is recognized by an ubiquitous factor, BMFA, which
      exhibits cyclical modifications in relation to the moulting cycle and could thus
      be involved in the temporal control of the gene during the development. A
      construct containing a reporter gene fused to 1450 bp of P25 5' flanking
      sequences was integrated into the Drosophila genome and shown to be specifically
      expressed in the larval salivary gland, the organ homologous to the silkgland.
      Recurrent deletions of this construct showed that the proximal 254 bp contain all
      the sequences required for this specific expression. Similar foreign constructs
      introduced in the silkgland in vivo by a particle delivery system were
      specifically transcribed in the posterior silkgland but remained silent in the
      middle silkgland as the endogenous genes. This methodology will be used to assay
      the function of the defined cis-acting elements in the spatial regulation of
      expression of P25.

PMID- 8574199
TI  - Simulation of the effects of loudness recruitment on the intelligibility of
      speech in noise.
AB  - This experiment simulated the threshold elevation and loudness recruitment
      associated with three different types of hearing loss: moderate flat (condition
      R2), severe flat (condition R3), and moderate-to-severe sloping (condition RX).
      This was done to allow an examination of the effects of these factors on the
      intelligibility of speech, in isolation from other factors that are normally
      associated with cochlear hearing loss, such as reduced frequency selectivity. The
      speech was presented at a fixed input level of 65 dB SPL, against a background of
      a noise whose spectrum was shaped to match the long-term average spectrum of the
      speech. The level of the background noise varied from 65 to 74 dB SPL. The
      simulation was performed by splitting the input signal into 13 frequency bands,
      and processing the envelope in each band so as to create loudness sensations in a
      normal ear that would resemble those produced in an impaired ear with
      recruitment. The bands were then recombined. All tests were performed using
      subjects with normal hearing. The simulation of hearing loss produced decrements
      in performance. The speech in condition R3 was inaudible. For conditions R2 and
      RX, the speech-to-noise ratios had to be up to 6 dB higher than in the control
      condition (R1, unprocessed stimuli) to achieve similar levels of performance.
      When linear amplification according to the NAL prescription was applied before
      the simulation, performance improved markedly for conditions R2 and RX, and did
      not differ significantly from that for R1. For condition R3, performance with
      simulated NAL amplification remained below that for condition R1; the decrement
      in performance was equivalent to about a 1 dB change in speech-to-noise ratio.
      The results of the present experiment show much smaller decrements in performance
      than those of an earlier experiment using a single talker as the interfering
      sound (Moore and Glasberg, 1993). It appears that loudness recruitment and
      threshold elevation have larger effects for a fluctuating background sound than
      for a steady background sound, and linear amplification is more effective in the
      latter case.

PMID- 8574198
TI  - Invasive tumors induce c-ets1 transcription factor expression in adjacent stroma.
AB  - The stroma reaction plays a central role in tumor growth, invasion and
      metastasis. Tumor growth is dependent on angiogenesis and requires the vascular
      supply provided by new capillary blood vessels of the stroma. The expression of
      the gene encoding the transcription factor c-ets1 is localized within fibroblasts
      and endothelial cells of the stromal compartment. This expression correlates with
      the accumulation of transcripts for potential target genes such as collagenase I
      and stromelysin I in stromal fibroblasts surrounding malignant cells in invasive
      tumors. We suggest that c-Ets1 protein might regulate the transcription of the
      genes coding for matrix-degrading proteases necessary for both angiogenesis and
      tumor invasion.

PMID- 8574200
TI  - Acoustic reflex measures at high probe frequency: a phasor diagram approach.
AB  - Acoustic reflex measures at high probe frequencies (above 660 Hz) have not been
      extensively reported in the published literature. Studies of the acoustic reflex
      at low probe frequencies conflict as to the effect of the reflex on resistance,
      although all researchers agree that the reflex increases the amount of negative
      reactance (stiffness). These differences may reflect methodological differences
      across studies. Lutman and his associates (Lutman and Martin 1979; Lutman et al.,
      1984) have used phasor diagrams to provide evidence for the effect of the reflex
      being on reactance, with constant resistance for low probe frequencies (220 and
      660 Hz). The present study incorporated the use of this method in order to
      investigate the effect of the reflex at a 1000 Hz probe frequency in 30 normal
      ears. Phasor diagrams of probe tip susceptance and conductance values obtained
      for three stimuli at a 1000 Hz probe frequency were analysed qualitatively.
      Eighty-two out of a total of 90 phasor diagrams obtained were matched to the
      constant-resistance stiffness-change model, suggesting that similar effects of
      the reflex are seen at low and high probe frequencies in most cases. This was
      noted to be the case for ears that were either stiffness-dominated or at their
      natural frequency at the 1000 Hz probe. However, the effect of the reflex on mass
      dominated systems was less clear and needs further clarification.

PMID- 8574201
TI  - An optimal filtering technique to reduce the influence of low-frequency noise on
      click-evoked otoacoustic emissions.
AB  - There is a need for methods capable of increasing the detectability of transient
      evoked otoacoustic emissions (TEOAE). Detection of an emission is based commonly
      on either visual inspection and cross-correlation between replicate recordings or
      cross-spectral analysis. Performance of these methods is obviously influenced by
      the residual noise level. Residual noise is often of low frequency and can be
      reduced by digital off-line filtering. For this purpose, an optimal high-pass
      filtering technique is proposed. Cross-correlation between replicates of TEOAEs
      was used to determine the cut-off frequency that maximizes the signal-to-noise
      (S/N) ratio. This is shown in a series of responses characterized by various S/N
      ratios. Data have been scored both visually and with quantitative methods before
      and after the use of high-pass filtering. The capability to detect the signal was
      increased with only a marginal decrease in the total power of the emissions.

PMID- 8574202
TI  - Selecting the gain for radio microphone (FM) systems: theoretical considerations
      and practical limitations.
AB  - This paper provides theoretical estimates of the signal-to-noise (S/N) ratio
      advantage that can be gained from a radio microphone (FM) system used with an
      environmental (EV) microphone, compared with the S/N ratio delivered by a
      conventional hearing aid alone. These estimates show that the S/N advantage
      gained is a function of the speaker/listener distance and the FM/EV gain
      difference, the greater the distance and the closer the FM gain is to the EV
      gain, the greater the S/N advantage. The implications for choice of FM and EV
      gain when fitting FM systems are discussed. The two goals of equating the FM and
      EV outputs and maximizing the S/N ratio are mutually incompatible. It is
      concluded that the FM gain should be set to be 10dB less than the EV gain unless
      the situation can be closely monitored, in which case the FM gain should be set
      as high as possible consistent with loudness tolerance and acceptable levels of
      distortion.

PMID- 8574203
TI  - Choosing talkers for the BKB/A Speechreading Test: a procedure with observations
      on talker age and gender.
AB  - A procedure is described for choosing talkers for the BKB/A (BKB/Australian
      version) Speechreading Test. The main aims were: to select several talkers from a
      pool of potential talkers, to avoid adventitiously choosing a markedly atypical
      single talker; to assess speechreading as a general skill rather than as talker
      specific; and to select talkers who were acceptable to speechreaders, relatively
      easy to speechread, and comparable in their speechreadability. Because of the
      number of variables involved and the demanding nature of the task for
      speechreaders, a three-stage selection procedure was adopted. In the resulting
      BKB/A 21-sentence list Speechreading Test, four of the 16 sentences in a list are
      each spoken by four talkers, chosen as follows. In Stage 1, 16 talkers (four of
      each age/gender set: older men, older women, younger men, younger women) were
      selected from an original pool of 40 (10 of each set), via rankings made by eight
      hearing-impaired judges with speechreading experience. In Stage 2, the final four
      talkers (one of each set) were selected from the 16 via the speechreading scores
      of further hearing-impaired subjects with speechreading experience. In Stage 3,
      the order of talker appearance within lists (in random order versus over blocks
      of four consecutive sentences) was determined. This three-stage approach to
      talker selection identified differences between talker candidates within sets,
      except for younger men, and suggested that, overall, younger women were the
      easiest to speechread. The discussion addresses the merits and disadvantages of
      this approach to talker selection, and suggests some reasons for the documented
      differences in speechreadability among talkers of different age and gender.

PMID- 8574204
TI  - Audiometer calibration: applying the earphone to the coupler.
AB  - A mechanism for applying an audiometric earphone to a coupler or artificial ear
      is described. The method ensures that the earphone is applied with the correct
      alignment and coupling force.

PMID- 8574205
TI  - National Advisory Committee on Immunization (NACI). Supplementary statement on
      Typhim VI polysaccharide capsular vaccine.

PMID- 8574206
TI  - National Advisory Committee on Immunization (NACI). Anaphylaxis: statement on
      initial management in non-hospital settings.

PMID- 8574207
TI  - Canadian recommendations for the prevention and treatment of malaria among
      international travellers. Committee to Advise on Tropical Medicine and Travel
      (CATMAT).

PMID- 8574208
TI  - Quality of life: an overview of the concept and measures.
AB  - This paper summarizes the concepts and measures of quality of life. Although
      numerous attempts have been made to conceptualize and operationalize quality of
      life, there has been no universally accepted standard for the study design, data
      collection and data analysis of studies that use quality of life as an outcome
      measure. Quality of life has been defined either as a measure of happiness and
      satisfaction with life, or goal achievement, or social utility. However, most
      studies conceptualize and measure quality of life as a composite that consists of
      several domains. There are two approaches to the measurement of quality of life,
      namely, the psychometric approach and the utility approach. A quality of life
      measure can be either generic or disease-specific. High reliability and validity
      are important criteria for a credible quality of life instrument. Published
      clinical studies which use quality of life as an outcome measure have to be
      assessed on the basis of the appropriateness of the study design, the validity of
      study results and the applicability of the quality of life measure to the
      specific patient group.

PMID- 8574209
TI  - The best of times, the worst of times. The global challenge of antimicrobial
      resistance.
AB  - The development of resistance to antimicrobial agents by many bacterial pathogens
      has compromised traditional therapeutic regimens, making treatment of infections
      more difficult and frequently more expensive. Three factors have contributed to
      the development and spread of resistance: mutations in common genes that extend
      their spectrum of resistance, transfer of resistance genes among diverse
      microorganisms and increases in selective pressures in and outside of the
      hospital environment that enhance the development of resistant organisms. Some
      new resistance mechanisms are difficult to detect in the laboratory. Thus,
      resistant microorganisms may go unnoticed until they are widely disseminated in a
      hospital. The challenge for pharmacists, microbiologists and physicians is not
      only to contain the spread of existing resistant organisms, but also to prevent
      the emergence of new resistant pathogens by encouraging the rational and prudent
      use of antimicrobial agents.

PMID- 8574210
TI  - Potential drug--drug interactions in 5,125 mostly elderly out-patients in
      Gothenburg, Sweden.
AB  - Of 5,125 mostly elderly out-patients, average age 78.2 years, 1,594 (31%) had at
      least one interacting drug combination according to the Swedish National
      Formulary. On average, each patient with drug-drug interactions (DDIs) had 1.6
      DDIs. There was no difference in the sex or age between those having DDIs and
      those without. However, patients with one or more DDIs used a significantly
      larger number of drugs than those without DDIs, on average 8.1 versus 5.2. This
      significant difference was independent of age and sex. When classified for
      clinical significance according to the handbook "Drug Interactions and Updates"
      by Hansten and Horn, 155 (3%) patients had interactions of 'major clinical
      significance'. The most common were interactions between beta-adrenergic blockers
      and antidiabetics, followed by potassium-sparing diuretics and potassium, and
      carbamazepine and dextropropoxyphene. The methodology allows us to screen
      routinely for DDIs and to plan further studies with emphasis on clinical outcome.

PMID- 8574211
TI  - Change in prescribing patterns of general practitioners in Italy before and after
      the Reform Drug Act. A case study of changes in the city of Turin.
AB  - As of 1 January 1994, the introduction of a new classification of the drugs to be
      reimbursed by the National Health Service was approved by the Italian parliament
      in order to limit expenditure on pharmaceutical agents. This has set off a
      'cultural revolution', unprecedented in Italy. The criteria that inspired the
      expert group charged with attributing drugs to different classes (Class A:
      essential, free of charge drugs; Class B: drugs to be paid for 50% by the
      patient; Class C: drugs to be paid entirely by the patient) were principally
      scientific rather than merely economic or administrative. Expectedly, the
      creation of Class C (drugs not reimbursed by the National Health Service on
      account of their insufficiently proven clinical effectiveness, or their
      unfavourable cost/benefit ratio with respect to therapeutically equivalent
      agents) has provoked remarkable changes in general practitioners' prescription
      options, particularly given the fact that many of these drugs were among the most
      prescribed in Italy. A database including the prescriptions of about 940 general
      practitioners, dispensed through the 280 community pharmacies of the city of
      Turin, has been analysed for a comparative sample of time periods in 1993 and
      1994, in order to quantify the changes that occurred and to qualify them with
      respect to more relevant therapeutic groups and sentinel drugs.

PMID- 8574212
TI  - Improving the quality of antimicrobial drug use can result in cost containment.
AB  - Antibiotic policies are implemented to optimize patient care, to limit
      antimicrobial resistance and to reduce costs. Before improving the use of
      antimicrobial drugs by monitoring, it is of primary importance to conduct a
      general utilization review to document problem areas within the hospital and to
      evaluate quality and costs. Subsequently, limited targets for an intervention can
      be defined. For the evaluation of quality, established criteria can be used to
      classify prescriptions into categories of appropriate use. Several classification
      systems are described in the literature. We have developed a classification
      method which allows evaluation of each relevant parameter associated with
      antimicrobial drug use and global (true) cost calculation. Data are processed in
      a computer program for Apple or Windows. Surgical prophylaxis is a target of
      choice to analyse at a hospital pharmacy level. Important cost savings can be
      obtained by implementing well-accepted standards of good antimicrobial
      prophylaxis.

PMID- 8574213
TI  - Adverse reaction to streptokinase with multiple systemic manifestations.
AB  - We report the case of a 47-year-old woman with a history of mitral valve
      replacement with a mechanical prosthesis who was admitted to the hospital with a
      3-month history of progressive exertional dyspnoea and was diagnosed as suffering
      from prosthetic valve thrombosis. Two consecutive courses of streptokinase were
      given as an intravenous infusion over 90 min at a dose of 1,500,000 IU each.
      Twenty minutes after the start of the second infusion (3 h and 20 min after the
      first one) she developed chills, fever, tachycardia and hypotension: symptomatic
      treatment was given and the infusion was completed. Two days later jaundice and
      choluria appeared with laboratory findings of hepatic cytolysis and cholestasis
      and renal insufficiency. The results of extensive microbiological and
      immunological investigations were not revealing. All the laboratory values
      spontaneously returned to baseline levels over the next 4 weeks. These
      abnormalities were attributed to an allergic reaction to streptokinase, although
      the exact pathogenic mechanisms involved are not known. We believe that further
      studies to elucidate the mechanism involved in the production of these effects
      are warranted in view of their potential clinical severity.

PMID- 8574214
TI  - Cost-evaluation model for clinical trials in a hospital pharmacy service.
AB  - A cost-evaluation model was applied to clinical trial protocols to estimate their
      cost for the hospital pharmacy service. The steps taken in the drug management of
      clinical research were identified. Fixed costs (common to all clinical trials)
      and variable costs (peculiar to each clinical trial) were determined for each
      step. The number of patients, the number of operations, the planned services
      (receptions, storage, drug dispensing), the timing and difficulty of the study
      (randomization) were included in the variable costs. The economic assessment of
      these items was based on the costs of the materials and means used, the cost of
      staff time and finally the cost of drug storage during the clinical trial. This
      model was applied to 24 clinical trials carried out in the University Clinic of
      Navarra. 83% of all pharmacy costs of a clinical trial were variable. Drug
      dispensing, stock management and return drugs account for 94% of the time
      expended. The approximate cost of the pharmacy providing investigational services
      was $1,766 per trial or $174 per patient. Drug storage costs were not an
      important source of expenditure among the variable costs (7.4%). The best way to
      determine the cost of a trial is to calculate the number of operations.

PMID- 8574215
TI  - A comparative study of the desquamation of urothelial cells during gestation and
      in adults mice following moderate stress or endotoxin treatment.
AB  - The present paper deals with the comparative EM study of the detachment of mouse
      urinary bladder epithelial cells under various physiological conditions, namely,
      during gestation and in adult mice following induction by endotoxin or by
      exposure to moderate stress. It has been shown that desquamation during gestation
      involves two distinct modes, shedding of single cells and formation of apoptotic
      bodies. Moderate stress in adult female mice induced by constant illumination for
      72 or 96 hours, results in desquamation of superficial and intermediate cells.
      Application of LPS is followed by desquamation of single cells and whole sheets
      of cells. Cell detachment involves interruption of tight junctions between
      neighbouring cells and formation of numerous cup shaped vesicles, multivesicular
      bodies and vacuoles at the base of desquamating cells. LPS induces desquamation
      entails delivery of lysosomal enzymes extracellulary into the intercellular
      space. In the areas of sloughing the bladder epithelium lack permeability
      barrier. Desquamated cells in the bladder lumen are mostly alive. These results
      clearly demonstrate the existence of specific adhesion mechanisms of detachment
      and desquamation of uroepithelial cells.

PMID- 8574216
TI  - Retinoic acid induces changes in Xenopus embryo glycolipid pattern.
AB  - Retinoic acid (RA), known for its important role in cellular differentiation, may
      cause a modification of glycolipid distribution characterized by a shift from
      globoserie towards latto- and ganglio-series. In the present paper, we have
      investigated the modifications of the lipidic pattern after exogenous RA
      treatment of Xenopus embryos. We have noticed a decrease in neutral glycolipids
      with a parallel increase in gangliosides; the content of sulfatides does not seem
      to be modified. Beside the shift toward ganglio-serie, we have also observed a
      redistribution inside this class of lipids. In particular, following RA
      treatment, the relative distribution of GD1b and GT1b increases while that of GM3
      decreases.

PMID- 8574217
TI  - Tyrphostin induces non-apoptotic programmed cell death in colon tumor cells.
AB  - The programmed cell death inducing effect of the EGF receptor tyrosine kinase
      inhibitor alpha-cyano-3,4-dihydroxycinnamthioamide (AG213) was investigated in
      vitro on HT-29 human colon tumor. AG213 at concentrations between 45 to 450
      microM blocks the proliferation of HT-29 cells. Morphological findings suggest
      that the selective tyrosine kinase inhibitor AG213 induces Clarke III type (non
      lysosomal vesiculate cytoplasmic) programmed cell death; unlike ATP analog non
      selective tyrosine kinase inhibitors like Genistein which were found to induce
      apoptosis. Cycloheximide and Actinomycin-D reduced the effect of AG213 pointing
      to the fact that protein and RNA synthesis are also needed for this form of cell
      death. Acid phosphatase activity was found in the Golgi and in the newly formed
      intracytoplasmic vacuoles 3 hours after AG213 treatment which disappeared by 6
      hours. The induction of Clarke III cell death by tyrosine kinase inhibitors may
      open a new modality to selective killing of tumor cells.

PMID- 8574218
TI  - Alkaline phosphatase distribution in the plasma membrane of uterine epithelial
      cells is markedly altered during early pregnancy in the rat.
AB  - Ultrastructural and light microscopic cytochemical methods were used to study the
      distribution and changes in distribution of alkaline phosphatase in the apical
      plasma membrane of rat uterine epithelial cells during different stages of early
      pregnancy up to the time of attachment of the blastocyst. Reaction product
      generated by alkaline phosphatase (AP) was located along the apical plasma
      membrane at each stage investigated. However, a very different organization of
      reaction product was observed depending on the time during early pregnancy with a
      continuous pattern appearing all along the microvilli on day 1. This pattern was
      subsequently converted into a clumped and highly 'patchy' appearance around the
      time of blastocyst attachment by day 6 of pregnancy. This change in pattern and
      distribution was only seen on the luminal epithelial cells with glandular
      epithelial cells and blood vessels displaying an unchanging distribution.

PMID- 8574219
TI  - Cell death of human multinucleated giant macrophages induced by conditioned
      medium obtained from rat liver cells.

PMID- 8574220
TI  - Reduction of extracellular superoxide dismutase activity by decapeptide derived
      from FGF-receptor.
AB  - Several synthetic decapeptides containing an HAV tripeptide motif were tested for
      their ability to modulate the enzymatic activity of rat extracellular SOD, an
      enzyme which also contains an HAV motif. Out of nine decapeptides that were
      tested, only a FGF-receptor derived peptide was active as a negative modulator of
      enzyme activity. These results strengthen the thesis that HAV motifs are not only
      involved in homophilic interactions and suggest that soluble FGF-receptor
      molecules might moderate the activity of extracellular SOD.

PMID- 8574221
TI  - International Symposium on Cell Proliferation. Innsbruck, Austria, November 30
      December 1, 1995. Abstracts.

PMID- 8574222
TI  - [Old misfortunes and new plagues: the fate of the infection specialist].

PMID- 8574223
TI  - [Morphometrics of the small intestine in children with diarrhea due to classical
      enteropathogenic Escherichia coli and to environmental asymptomatic enteropathy].
AB  - The enteric EPEC infection may cause different degrees of abnormalities in the
      small bowel villi. Morphological changes in the small intestine have been
      described in asymptomatic children who live in unfavourable environmental
      conditions. Enteric EPEC infections frequently occur in children living in such
      conditions and may worsen the already existing lesions. OBJECTIVES--1) To
      evaluate the morphological changes of the morphometry and compare them to the
      intestinal mucosa of children bearing Asymptomatic Environmental Enteropathy
      (AEE). 2) To compare the number of intra-epithelial lymphocytes (IEL) found in
      acute and/or persistent diarrhea by EPEC to those ones found in the other two
      groups. MATERIAL AND METHODS--Thirty (30) specimens of small intestinal mucosa
      obtained from children having acute and/or persistent diarrhea by EPEC were
      analysed and then compared to the specimens of the small intestinal biopsy of
      sixteen (16) patients bearing AEE. The following measurements were performed:
      RESULTS-- [table: see text] CONCLUSIONS--The villous changes were more remarkable
      in EPEC infection but the crypt hypertrophy was significantly higher in patients
      with AEE. This fact is probably due to repeated damages caused by the
      environmental problems. The use of linear morphometry has been a relevant
      technique which allows to evaluate the possible small intestinal morphological
      changes more accurately than the subjective criteria. In this way, the
      application of this technique enables the comparative approach of determined
      values under statistical bases.

PMID- 8574224
TI  - [Clinical and surgical importance of anatomosurgical segments and subsegments of
      the organs of the human body].
AB  - OBJECTIVE: To emphasize the ubiquity of the anatomicosurgical segments and
      subsegments and to underscore their clinical and surgical importance, based upon
      recent advances in morphology, physiology, pathology, internal medicine and
      surgery. PURPOSE: To update basic knowledge of the structure and its application
      in modern medicine and surgery, for more conservative approach to treat diseases
      of organs in most systems of the body. METHOD: Comparative study of the anatomico
      surgical segments and subsegments already described. RESULTS: The data show that
      the concept of anatomicrosurgical segmentation is applicable to practically all
      organs. CONCLUSION: The segmentation of the structures of the body from the
      anatomical and surgical standpoints is another general principle of construction
      of the human body and of other mammals as well as in vertebrates. Such a new
      approach to evaluate the vascular and ductal components of each organ opens
      broader horizons to the treatment of diseases.

PMID- 8574225
TI  - [Survival of dialyzed diabetic patients].
AB  - OBJECTIVE: Diabetes is a cause of end-stage renal failure of increasing
      importance. Our aim was to evaluate the survival of diabetic and non-diabetic
      patients on dialysis treatment. MATERIAL AND METHODS: Two hundred and ninety-five
      patients on dialysis program in a tertiary referral center of the Sao Paulo city,
      from 1992-94, were studied. Seventy-one patients were diabetics (17 type I and 54
      type II) and 224 had other diagnoses of renal disease. Data were prospectively
      collected using standard questionnaires and also retrospectively for patients who
      started treatment between 1992 and June 1993. Survival analysis was done using
      the product-limit method. RESULTS: Diabetic patients had a greater mean age and a
      higher proportion on peritoneal dialysis than non-diabetics. After one year,
      survival rates were 67% and 86% for diabetics and non-diabetics (p < 0.0001). The
      difference in survival rates increased with the duration of treatment. This
      difference was observed both in young (< or = 50 years) and in elderly patients,
      although it has been noted earlier in the former. Survival of diabetics remained
      significantly reduced adjusting for the age of the patients. CONCLUSIONS:
      Diabetic patients on dialysis have lower survival rates than non-diabetics,
      independently of their greater mean age. Special attention should be given to
      these patients, both in relation to pre-dialysis comorbidity and during dialysis
      treatment, to improve their survival experience.

PMID- 8574226
TI  - [Comparison of the determination of cyclosporin-A in blood samples collected on
      filter paper and by the ordinary technique].
AB  - Monitoring cyclosporin-A (CsA) blood levels is of utmost importance for the
      rational use of this drug. Although many centers perform transplants, in Brazil
      there are few laboratories able to measure CsA blood levels. Therefore making
      blood samples reach the laboratory emerged as a problem. Collection of blood on
      filter paper has been a technique used for a long time in special cases. PURPOSE-
      To confirm the usefulness of measuring CsA blood levels in blood samples
      collected on filter paper and in the usual way. METHOD--We studied twenty renal
      cadaver kidney recipients who were receiving CsA, azathioprine and prednisone.
      Ninety five blood samples were collected and divided into two aliquots. One of
      them was sent routinely to one laboratory to perform whole blood CsA
      measurements. From the other aliquot, 20 microliters were pipetted on filter
      paper. When dried they were mailed to the other laboratory, where, after elution,
      CsA was measured. In both cases radioimmunoassay with polyclonal antibody was
      used. RESULTS--Linear correlation between both measurements revealed r = 0.81
      with no statistical difference. CONCLUSION--The technique showed to be useful in
      clinical practice. In countries with continental size, as Brazil, it may be very
      helpful.

PMID- 8574227
TI  - [Histopathological changes in the small intestine after hypothermic preservation
      with University of Wisconsin and Euro-Collins solutions. Experimental study].
AB  - PURPOSE: The objective of this study is to compare small bowel histopathologic
      alterations under hypothermic preservation with University of Wisconsin (UW) and
      Euro-Collins (EC) solutions. METHODS: In 40 Wistar rats (250-300g) the small
      bowel was microsurgically withdrawn and randomly treated with UW solution or EC
      solution. Periodic intestinal biopsies were taken from the proximal jejunum and
      distal ileum each 8 hours after small bowel withdrawing (time 0) until 48 hours.
      The histopathologic alterations were semiquantitatively classified in 4 degrees
      of severity and the obtained results were analysed statistically by appropriated
      tests (p < 0.05). RESULTS: There was a significant increase of the small bowel
      ischaemic lesions over the time for both experimental groups. The lesions
      frequency and severity were significantly more increased in the EC group than in
      the UW group, for jejunal segments at 8 hours, in jejunal and ileal segments at
      24 and in jejunal and ileal segments at 48 hours. CONCLUSION: The UW solution did
      not avoid the development of small bowel ischaemic lesions but, with time, it
      protected better jejunal and ileal segments, decreasing frequency and severity of
      histopathological alterations, when compared to EC solution.

PMID- 8574228
TI  - [Chlamydia trachomatis infection and risk factors in pregnant women].
AB  - INTRODUCTION: In order to assess the frequency of Chlamydia trachomatis infection
      in pregnancy in Sao Paulo (Brazil), a group of 122 successive pregnant women (80
      adults and 42 adolescents) attending the pre-natal care clinic of the Department
      of Obstetrics were studied. MATERIAL AND METHODS: The exam consisted of an
      epidemiological survey, a complete obstetrical clinical examination and the
      assessment of the presence of C. trachomatis in the vagina by ELISA
      (Chlamydiazyme). RESULTS: A total of 11 women (9%) were positive, being 8 (10%)
      of them adults and 3 (7%) adolescents. CONCLUSION: In Sao Paulo the age of the
      patient as well as the marital status, the number of sexual partners, the
      existence of other sexually transmitted diseases, the presence of cervicitis or
      the occurrence of abortions could not be considered as risk factors for the
      presence of the Chlamydia trachomatis.

PMID- 8574229
TI  - [Serial ultrasonography of the endometrium and endocervix during the normal
      menstrual cycle in women].
AB  - Articles on ultrasound of the human endometrium are in the majority of the cases
      based on studies of patients who have infertility and are taking drugs to induce
      ovulation. Such investigations do not include histological study of the
      endometrium and have focused on the ovulatory period. There is controversy in the
      interpretation of the images. PURPOSE--To evaluate the sonographic appearance of
      the endometrium during the normal menstrual cycle. METHODS--We studied 15
      multiparous women with normal cycles, and who were not under drugs for ovulation
      induction, had neither IUD, nor were having oral hormonal contraceptives. They
      were seen on the first, seventh, fourteenth, and twentieth-first days of the
      menstrual cycle. The sonographic aspects were compared with the histological
      findings. RESULTS--We could see the images of the endometrium on the first day of
      the cycle in 66.66% of the patients. On the other visits we could study properly
      its features very well in all the patients. The endometrial image thickness
      increased in a linear pattern and the hypoechogenic halo was seen in 93.33% of
      the patients on the twentieth-first day of the menstrual cycle. CONCLUSION--The
      cyclic changes of the endometrium were shown with the sonography. The cyclic
      changes of the endocervix were evaluated too with the sonogram although they are
      not as remarkable as the endometrial ones.

PMID- 8574230
TI  - [Assessment of iron status in individuals with heterozygotic beta-thalassemia].
AB  - Idiopathic haemochromatosis and thalassemia are the most frequent genetic
      disorders associated to iron overload. In major and intermedia thalassemia
      patients, the iron overload is a well defined situation; however in minor
      thalassemia, frequently an asymptomatic disease, there is no agreement about the
      situation of iron storage. The best index for evaluation of the iron state is
      serum ferritin, because there is a correlation between its value and iron hepatic
      concentration. PURPOSE--Iron state was studied in a homogenous group of
      Brazilians with beta-thalassemia trait and the correlation between iron state and
      anemia severity was verified. METHODS--35 adult subjects with beta-thalassemia
      trait and 35 normal subjects (20 women and 15 men, aged between 20 to 54
      years/group) were studied for serum iron, TIBC, serum ferritin and hemoglobin.
      RESULTS--The results demonstrated that in the male group of beta-thalassemia
      trait subjects the mean value of serum ferritin was 253.69ng/mL and in the male
      control group it was 107.79ng/mL (U calc < U crit). There was no statistic
      difference between any studied variable in female groups. There was no
      correlation between the iron state and the hemoglobin levels in beta-thalassemia
      trait subjects. CONCLUSION--The possibility of iron overload in males with beta
      thalassemia trait and the necessity to follow-up those subjects with high levels
      of serum ferritin is suggested.

PMID- 8574231
TI  - [Colchicine in chronic liver disease of alcoholic etiology. Double-blind,
      randomized study of its effects on blood levels of plasma proteins and clinical
      course in patients].
AB  - Patients with alcoholic chronic liver disease when treated with colchicine during
      a 12 month-period improved significantly the plasmatic levels of albumin and
      prothrombin when compared with a similar group of patients who took placebo. No
      differences in the mortality rate and in number of patients admitted at the
      hospital could be detected among those groups during this period. PURPOSE: To
      evaluate the clinical outcome and the plasmatic levels of albumin, pre-albumin,
      prothrombin and transferrin in patients presenting alcoholic chronic liver
      disease taking colchicine or placebo, during a 12-month period. METHODS: In a
      double-blind, randomized, controlled trial, 41 patients with alcoholic chronic
      liver disease were assigned to either placebo (20 patients) or a colchicine (21
      patients) treatment group, assessing their clinical course (mortality rate and
      hospital admission) and plasmatic protein levels during a 12-month period.
      Albumin, pre-albumin and transferrin plasmatic levels were assessed through a
      immunodiffusion radial method and prothrombin time and activity was assessed by a
      one stage Quick modified method. RESULTS: At the end of the trial, only 7.3% of
      the patients were lost during follow-up. No statistical differences could be
      found in mortality and number of patients admitted at the hospital among placebo
      and colchicine groups. Comparatively to the placebo group, a significant increase
      in the mean of percentage variation was found in patients of the colchicine group
      for serum albumin levels (17.9% colchicine x 3.6% placebo, p < 0.05) and for
      prothrombin activity (19.2% colchicine x 2.1% placebo, p < 0.05). A similar
      pattern of response was found in pre-albumin serum levels, but such differences
      were not statistically different. No differences were found in serum transferrin
      levels among both groups. CONCLUSION: These results suggest that colchicine
      intake has a positive effect on plasmatic protein levels in patients with
      alcoholic chronic liver disease.

PMID- 8574232
TI  - [Complications of allogeneic microsurgical transplantation of a limb (composite
      tissue), in rats].
AB  - PURPOSE: To analyze the composite tissue vascularized allotransplantation post
      operative complications and to identify factors associated with agents toxicity.
      METHOD: The study was done across a strong histocompatibility barrier using 39
      Brown-Norway rats as donors and 78 Fischer 344 as hindlimb allotransplantation
      recipients treated with cyclosporine and RS-61443. RESULTS: 1 (1/78: 1.28%) was
      eliminated owing to thrombosis; 2 (2/78: 2.56%) owing to enteritis; 1 (1/78:
      1.28%) owing to autophagia and 8 (8/78: 10.42%) died owing to undiscovered cause.
      CONCLUSION: Among 78 (78/78: 100%) rat limb vascularized allotransplantations, 12
      (15.5%) rats died or were eliminated because of acute postoperative complications
      that were not related to rejection, to immunosuppressive toxicity or to
      opportunistic infection.

PMID- 8574233
TI  - [Abdominal liposarcomas].
AB  - Abdominal liposarcomas are a rare group of tumors and their principles of
      treatment are based in accumulated experiences of retrospective series. PURPOSE-
      To report seven cases of abdominal liposarcomas and to discuss the main
      diagnostic and therapeutic aspects of these tumors nowadays. METHODS--Seven
      patients operated for abdominal liposarcomas were in the Surgical
      Gastroenterology Discipline of Escola Paulista de Medicina (UFESP) during 30
      months. The major clinic, ultrasonographic, tomographic, surgical and
      histopathological features were collected in each case. RESULTS--Authors call
      attention to the unusualness of these tumors, their propensity (while primary) to
      grow in their own place, without invading the tissues around or metastasizing,
      and when they are recurrent to their more aggressive malignity. They consider
      that computerized tomography is the most useful diagnostic procedure and they
      discard the need of percutaneous biopsy (guided or not) in the preoperative
      period. They emphasize the fundamental role of radical excision surgery in these
      tumors treatment and also emphasize the importance of the resection with proper
      margins, even if an associated resection of visceral organs is necessary. They
      consider that now radiotherapy and chemotherapy are not very effective methods to
      the adjuvant treatment of these tumors. CONCLUSION--It is important an accurate
      follow-up of the operated patients in order to indicate, when necessary,
      repetitive resection surgeries, even if they are palliative (citoredution
      surgeries), with the purpose of improving the expectation of life.

PMID- 8574234
TI  - [Analysis of clinical parameters of elderly inpatients in an internal medicine
      ward].
AB  - A number of Brazilian studies have been done on elderly in-patients in a General
      Hospital but only one studied them in a Internal Medicine Ward. PURPOSE--To
      analyse morbidity and mortality comparing age and sex in the elderly in-patients
      in a General Hospital Internal Medicine Infirmary. METHODS--We analysed 163
      elderly patients (101 females, 62 males) who represent 42.3% of the total number
      of in-patients for 100 consecutive days; 84.1% whites and an average age of 71.4
      +/- 8.3 years. RESULTS--(p < 0.05): (1) Among elderly females--there was a high
      rate of heart failure as cause of hospitalization. (2) Among elderly males-
      stroke was the main cause of hospitalization. (3) Among 60-69 year old patients-
      diabetes mellitus was the main cause of hospitalization. (4) > or = 70--stroke
      was found to be the most frequent cause of hospitalization and high frequency of
      level F and G on the Katz Scale. Circulatory diseases were the cause for 42.3% of
      hospitalization. Dehydration was the main complication during hospitalization
      (46.0%). There were 38 deaths (23.3% of the patients), 50.1% were caused by
      respiratory diseases. CONCLUSION--The elderly are an important group of in
      patients in a General Hospital Internal Medicine Ward.

PMID- 8574235
TI  - [Use and causes of discontinuation of eye surgical interventions at a university
      ambulatory surgery center].
AB  - OBJECTIVE: To study the efficiency of an ambulatory surgery center located at a
      university public hospital we studied the number of surgical interventions
      performed and suspensions and their causes. METHODS: We collected data on the
      number of surgical interventions performed, suspension and causes of suspension
      from January to December of 1992 of the ambulatory surgery center of the Clinical
      Hospital of University of Campinas, UNICAMP, in Sao Paulo. A comparison of
      performance of the Ophthalmology Department and the other medical specialties
      were made. RESULTS: Of the 6,574 surgical interventions booked 4,938 (75.11%)
      were performed and 1,636 (24.88%) suspended. Of the 4,938 surgical interventions
      2,514 (51%) were performed by the Ophthalmology Department and 2,423 (49%) by
      other 11 medical specialties. The main causes of suspension of eye operations
      were unfavorable clinical condition (46.38%), absence of the patient (32.71%) and
      administrative problems (8.44%). CONCLUSION AND SUGGESTIONS: The Ophthalmology
      Department has 40% of the space available at the facility and did 51% of the
      interventions. A better control and planning of the surgical operations may
      increase the number of interventions and performance of the ambulatory surgery
      center. It is important for the optimization of the available resources to
      introduce a periodic control of surgical interventions done, suspension and their
      causes.

PMID- 8574236
TI  - [Intraoperative evaluation of endometrial carcinoma staging].
AB  - The new International Federation of Gynecology and Obstetrics (FIGO) staging
      system for endometrial cancer is based on intraoperative examination of
      hysterectomy specimens not submitted to radiation. PURPOSE--This system aims to
      recognize the risk factors for intrabdominal lymph node metastases not detected
      by the earlier staging system, permitting to select the patients who must be
      submitted to lymphadenectomy. The major risks for metastases are: poorly
      differentiated neoplasms (grade 3), deep myometrial invasion (more than half of
      the thickness of the myometrium) and certain more aggressive histological types.
      METHODS--Intraoperative examination takes about 30 minutes. The uterus is
      laterally opened and several complete transversal cuts are made in order to
      choose the suspected deeper myometrial or cervical invasion areas for
      histological frozen examination. The findings were compared with the permanent
      slides. RESULTS--Good correlations between frozen and permanent sections were
      obtained, with an accuracy of about 90%. CONCLUSION--This new FIGO staging is
      under evaluation. The comparative results show a higher degree of confidence on
      the method performance. The complementary radiotherapic treatment is indicated
      according to the disease stage.

PMID- 8574237
TI  - [Neuroleptic malignant syndrome].

PMID- 8574238
TI  - [Hairy cell leukemia: review of the literature].

PMID- 8574239
TI  - [Spontaneous pneumothorax and breast cancer].
AB  - BACKGROUND: Spontaneous pneumothorax with concomitant neoplastic diseases is
      unusual. Lung cancer and osteogenic sarcoma with pulmonary metastasis are the
      neoplasms that most frequently accompany the spontaneous pneumothorax. This
      article's purposes are to relate the occurrence of spontaneous pneumothorax
      associated with breast neoplasms and to discuss the main etiopathogenic factors
      involved in the process. MATERIAL AND METHODS: The authors report a case of a 43
      year-old black woman carrier of a left breast ductal carcinoma with bilateral
      pulmonary metastasis. Spontaneous pneumothorax appeared during multidrug
      chemotherapy, so it cannot be related to other causes. CONCLUSIONS: Even though
      breast neoplasms cause lung metastases in about 60% of the cases, the coexistence
      of spontaneous pneumothorax and breast carcinoma is very rare. There was no
      report of this topic in the medical literature review during the last five years.
      The authors believe and discuss the multiple pneumothorax etiopathogenic factors
      related to this case.

PMID- 8574240
TI  - [Pseudothrombophlebitis syndrome in Reiter's syndrome].
AB  - Although the pseudothrombophlebitis syndrome has been studied for a long time it
      still presents some difficulties to be diagnosed and we can not distinguish it
      from real thrombophlebitis only by clinical methods. The author presents a
      Reiter's syndrome patient with recurrent Baker's cyst rupture that develops into
      pseudothrombophlebitis and discusses some aspects related to this diagnosis and
      treatment. He calls the attention to this diagnosis mainly in those patients
      presenting clinical signs of thromboplebitis of the inferior member and knee
      arthropathy.

PMID- 8574241
TI  - [Infection caused by Mycobacterium tuberculosis with primary resistance to
      multiple drugs: a case report of a patient with AIDS].
AB  - Primary multidrug-resistant Mycobacterium tuberculosis is an important problem in
      the United States. There is no report in formal literature of this pathogen in
      Brazilian patients. CASE REPORT--We report a case of ganglionar tuberculosis
      diagnosed by acid-fast smears in a male, HIV positive patient. Mode of
      acquisition of HIV was not determined. Treatment was started, and isoniazid,
      rifampicin and pyrazinamide were prescribed. The patient and his family reported
      strict adherence to therapy, but no improvement was observed. After 75 days, the
      patient was admitted in our hospital because of clinical worsening. Clinical
      features were the presence of large submandibular and axillar lymph nodes,
      respiratory insufficiency and complains of abdominal pain. He died six days after
      admission. Culture obtained from the ganglionar aspirate disclosed M.
      tuberculosis susceptible to ethambutol, but resistant to isoniazid, rifampicin,
      pyrazinamide, ethionamide and streptomycin. DISCUSSION--Although this was a case
      of extrapulmonary tuberculosis, there is a concern about multidrug-resistant
      tuberculosis, that has been poorly evaluated in Brazil. Since high lethality and
      intrahospital transmission have been reported, we discuss the need of performing
      culture and antibiogram in suspected cases, and the prevention of the spread of
      M. tuberculosis to patients and health-care workers through the strict adherence
      to the isolation practices.

PMID- 8574242
TI  - Vaccination of mice against Taenia taeniaeformis using antigen fractions
      partitioned with Triton X-114.
AB  - Taenia taeniaeformis oncosphere and metacestode antigens were fractioned using
      Triton X-114 into insoluble, aqueous and detergent rich fractions. These
      fractions were analysed in SDS-PAGE and immunoblots and used in vaccination
      trials against infection with T. taeniaeformis in mice. Qualitative differences
      were apparent in the spectrum of antigens partitioning into the different
      detergent phases but host-prospective antigens were present in all three
      fractions. The presence of individual antigenic components in the phases did not
      correlate with the degree of protection afforded by these fractions in the
      vaccination trials. Host protective immunogenicity of T. taeniaeformis oncosphere
      and metacestode extracts may be due to multiple protective antigens which
      partition into the different Triton X-114 fractions.

PMID- 8574243
TI  - EU experimental study on wild boar trichinellosis.
AB  - From January 1994 onwards the Council Directive 92/45 EEC concerning the
      examination of wild game meat for trichinellosis is valid. Laboratory methods
      required are identical to those used for the examination of pork. In an
      international experiment the suitability of these methods to control wild boar
      meat was tested. Required meat parts of experimentally with T. spiralis infected
      wild boars were shipped to seven laboratories in Europe under code. It was
      concluded that trichinoscopy and pool sample digestion methods meant for pork
      examination could equally well be used for control of wild boar meat. The so
      called Trichomatic method required a few adaptations. Moreover it was
      demonstrated that extra washing procedures were required to prevent cross
      contamination between samples with Trichomatic equipment.

PMID- 8574244
TI  - The mycobacterial component of complete Freund's adjuvant induces expulsion of
      the intestinal nematode Trichinella spiralis in mice.
AB  - Expulsion of T. spiralis adult worms was accelerated in high-responder NIH mice
      vaccinated previously with complete Freund's adjuvant (CFA) emulsified in PBS,
      whereas the expulsion of this parasite from low-responder C57 BL/10 mice was
      unaffected. Incomplete Freund's adjuvant (IFA) did not induce protection and it
      was concluded that the mycobacterial component, present in CFA but absent from
      IFA, was responsible for inducing these non-specific protective effects. CFA did
      not induce T. spiralis-specific B- or T-cell responses, but high levels of IFN
      gamma from Con A-stimulated mesenteric lymph node cells of CFA-vaccinated NIH
      mice were detected. Such cytokine release was not produced by cells from the C57
      BL/10 strain. It is therefore proposed that IFN gamma production is related to
      the mode of adjuvanticity and non-specific protective effects of CFA in this
      system.

PMID- 8574245
TI  - Prevalence of Mansonella perstans in western Uganda and its detection using the
      QBC-fluorescence method.
AB  - The prevalence of the apathogenic filaria Mansonella perstans was studied in four
      parishes in western Uganda as part of an onchocerciasis control programme to
      avoid futile treatment. Blood samples from 1543 persons aged over 14 years from
      19 villages were examined for the presence of microfilariae using a modified
      Knott method. The prevalence of microfilaraemic persons ranged between the
      parishes from 39% (95% CI 35.9-42.0%) to 81% (95% CI 76.2-84.8%). With exception
      of single microfilariae of Onchocerca volvulus no other filaria species was
      detected. Onchocerciasis mass treatment campaigns did not reduce the prevalence
      of M. perstans infection, since 6-12 months after treatment with a single dose of
      150 micrograms/kg ivermectin the prevalence in 124 persons was about the same as
      before treatment. The QBC-fluorescence technique was employed for the detection
      of microfilariae in samples from outpatients of the government hospital in Fort
      Portal: in 16% of 120 children and 24% of 369 adults microfilariae of M. perstans
      were detected.

PMID- 8574246
TI  - Use of an ivermectin bolus against gastrointestinal nematode and lungworm
      infections in first-year grazing calves.
AB  - Two groups of first-year grazing cattle each were either left untreated as
      controls (group 1) or treated with an ivermectin bolus at turnout (group 2).
      Whereas group 1 suffered from dictyocaulosis, the bolus treated calves remained
      healthy. Shedding of lungworm larvae was completed prevented and gastrointestinal
      nematode egg output effectively reduced. During the 154 day grazing season the
      ivermectin bolus provided a season-long protection against parasitic
      gastroenteritis and bronchitis.

PMID- 8574247
TI  - The use of short-term cultures of Pneumocystis for drug testing.
AB  - A method for short-term drug testing for Pneumocystis is described. Up to now
      there was no successful cultivation method without feederlayers. Parasites for
      inocula were obtained from nude rats, kept under conventional conditions.
      Pneumocystis separation was done by two centrifugation steps from lung
      homogenates. Cultivation in a modified Tegoshi medium resulted in preservation of
      parasites for five days, however there was no growth of P. carinii.
      Quantification was done microscopically by counting trophozoites in triplicate
      cultures. The percentage of cysts with intracystic bodies did not exceed 2% of
      parasites. Tests with pentamidine isethionate as a reference drug demonstrated
      the suitability of this system for drug evaluation.

PMID- 8574248
TI  - The Mongolian gazelle (Procapra gutturosa, Bovidae) as an intermediate host of
      three Sarcocystis species in Mongolia.
AB  - The sarcocysts of three Sarcocystis species (Sporozoa: Coccidia: Sarcocystidae)
      found in the Mongolian gazelle are described using light and transmission
      electron microscopy. The host-parasite interface and the ultrastructure of the
      cyst wall are represented for the first time in the macrocysts of Sarcocystis
      mongolica Machul'skii, 1947, localised in connective tissue cells. The cyst wall
      is attributed to type 1 of the classification by Dubey et al. (1989). Two other
      species are described for the first time from Procapra gutturosa in Mongolia: S.
      sp. with hair-like villar protrusions (type 7) and S. danzani n. sp. with villar
      protrusions possessing a structure hitherto unknown, characterised by a hollow.

PMID- 8574249
TI  - Ecological relations among first-stage larvae of four species of
      Protostrongylidae (Nematoda) within their ovine host.
AB  - Competitive relations between protostrongylid nematodes parasitic in the ovine
      lung, using competition coefficients and asymptotic densities showed that two
      relatively scarce species (Neostrongylus linearis and Protostrongylus rufescens)
      exert strong competitive actions on the two most abundant species (Cystocaulus
      ocreatus and Muellerius capillaris). P. rufescens could lead to the disappearance
      of the more abundant species, if other compensatory factors did not exist in
      their life cycle.

PMID- 8574250
TI  - Acanthocheilonema viteae: transplacental transmission of microfilariae from
      mother to offspring.

PMID- 8574251
TI  - Strategic effects of early season treatments with Moxidectin on
      trichostrongylosis in young calves.
AB  - This study was conducted to evaluate the effects of strategic early season
      treatments with Moxidectin on trichostrongyles in first-season grazing heifer
      calves on a permanent pasture. Three groups of Black-Pied Friesian heifer calves
      were turned out in early May on a permanent pasture naturally infected with
      trichostrongyle larvae. Two of these groups were treated with Moxidectin at
      turnout or at turnout and again 8 weeks later, while one group served as
      untreated controls. For the first three weeks of the experiment all animals
      grazed together in one flock on one pasture. Subsequently, the pasture was
      divided into three comparable plots, which from then and until housing in mid
      October were grazed by each calf group. The results showed that the treatments
      significantly suppressed faecal egg excretion in the early part of the season,
      leading to reduced herbage infectivity and parasitism over the rest of the
      season. Results from faecal egg counts determined at genus level revealed that
      the persistent activity of Moxidectin appeared to be longer against Ostertagia
      spp. than against Cooperia spp. Two Moxidectin treatments, given at turnout and
      on week 8, protected the calves to a higher degree than a single Moxidectin
      treatment given at turnout. However, there was also a significant effect of only
      one Moxidectin treatment which possibly could be explained by a low overwintered
      larval population and a drought period in the early summer.

PMID- 8574252
TI  - Balance of coagulation activity with fibrinolysis during use of oral
      contraceptives in women with insulin-dependent diabetes mellitus.
AB  - In healthy nondiabetic women, oral contraceptives (OCs) affect hemostatic
      function. In diabetic women, there is concern that they may also increase the
      risk of diabetic vascular complications. This study was designed to examine the
      balance between coagulation activity and fibrinolytic activity--an indirect
      measure of endothelial cell function--in women with insulin-dependent diabetes
      mellitus (IDDM) during long-term use of OCs. The study group included 11 young
      women with uncomplicated IDDM who were prescribed ethinyl estradiol 30 micrograms
      and gestodene 75 micrograms. Twelve other diabetic women not taking OCs
      constituted the control group. Hemostatic function was evaluated at entry and
      after 1,3,6, and 12 months. In women taking OCs, plasma levels of factor VII(c)
      increased, while fibrinogen levels did not change. Inhibition of coagulation was
      affected by increased levels of protein C, although plasma levels of antithrombin
      III and protein S remained stable. The antigen concentrations of tissue-type
      plasminogen activator and plasminogen activator levels themselves were unchanged.
      There was a proportionate increase in the concentrations of thrombin-antithrombin
      III complexes and D-dimer. None of the hemostatic variables changed significantly
      in the control group. We conclude that the balance between coagulation activity
      and fibrnolysis does not change during use of this OC. Our findings suggest that
      low-dose OCs induce a procoagulatory state that is compensated for by enhanced
      fibrinolytic activity.

PMID- 8574253
TI  - European Society of Contraception oral contraceptives survey update: birth
      control methods in "Europe of the 12".
AB  - The European Society of Contraception developed a survey to examine birth control
      methods in the 12 countries++ of the European Community. Responses to those
      questions relating to prescribing++ practices of oral contraceptives (OCs) are
      presented herein. The survey was sent to 400 physicians. One hundred two
      responded, most from France, Belgium, and the United Kingdom. The responses
      revealed that the most popular OCs are modern combined formulations containing
      low doses of ethinyl estradiol and progestogens such as norgestimate,
      desogestrel, gestodene, and levonorgestrel. More than half of physicians
      prescribe a particular formulation because of its tolerability and 20% because of
      its hormonal content. More than 90% prescribe OCs to healthy, nonsmoking women
      over 40. However, three fourths will not prescribe OCs to smokers over 35. Half
      of physicians recommend mammography for their older OC patients. Half also
      recommend cholesterol screening, but 8% only for women over 30. Most physicians
      are no longer reluctant to prescribe OCs to their diabetic patients: 61%
      prescribe OCs for women with non-insulin-dependent diabetes, 56% for those with
      insulin-dependent diabetes, and 85% for those with a history of gestational
      diabetes. Despite recent studies showing no relation between past OC use and
      cardiovascular disease, 42% of physicians said that their greatest OC-related
      health concern is cardiovascular disease. One third cited noncompliance as their
      greatest concern. These results reveal inhomogeneous prescribing practices for
      OCs among European physicians. ?Over-screening?--not prescribing the pill because
      of perceived (but not necessarily real) health risks--may be depriving many women
      of the contraceptive and noncontraceptive benefits of OCs. Complete and accurate
      information--as promoted by the European Society of Contraception--is one way to
      combat such overscreening.

PMID- 8574254
TI  - Adolescent pregnancy in Europe.
AB  - The International Federation of Pediatric and Adolescent Gynecology surveyed
      physicians from 11 European countries to ascertain the countries' adolescent
      pregnancy and abortion rates. Pregnancy rates tended to remain stable or decrease
      through the 1980s, with some notable exceptions. Germany, Federal Republic
      exhibited the highest adolescent pregnancy rates; the rate increased from 16% to
      21% among 16- to 18-year-olds from 1985 to 1987, and then decreased to 13% by
      1989. The United Kingdom had the second highest rate of adolescent pregnancy,
      although in the 16- to 18-year-old group, the rate decreased from 9.1% in 1985 to
      8.6% by 1989. The Netherlands and Denmark had the lowest adolescent pregnancy
      rates, with a cumulative total of 0.9% in both countries for adolescents under
      age 18 years in 1985 and 1987; data for 1989 were not available at the time of
      the survey. Abortion rates among adolescents--expressed as a percentage of the
      total number of abortions performed in each country--increased in most countries
      during the 1980s. By 1989, Hungary and Finland had the highest abortion rates,
      11% and 9.5%, respectively. Belgium had the lowest rate; only 1% of abortions
      performed were in women aged 18 years and younger. Most of the countries included
      in this survey require parental consent for termination of pregnancy. Although
      the medical complications of pregnancy and birth in adolescents can be minimized
      with good management and follow-up, the social and psychological implications
      continue to take a toll. Sex-education programs are one means of reducing the
      rate of adolescent pregnancy. For adolescents who do become pregnant, however,
      psychological and social support must be provided in addition to medical care.

PMID- 8574255
TI  - Termination of early pregnancy (up to 63 days of amenorrhea) with mifepristone
      and increasing doses of misoprostol [corrected].
AB  - The efficacy and tolerability of mifepristone in combination with misoprostol for
      termination of early pregnancy (up to 49 days of amenorrhea) are established. We
      studied the efficacy and tolerability of this combination therapy for termination
      of pregnancy in women up to 63 days of amenorrhea. We also examined the effect of
      an additional dose of misoprostol in cases of nonexpulsion within 3 hours after
      the first dose. The multicenter trial included 1,108 women, mean age 27.9 +/- 6.2
      years. The mean duration of pregnancy was 51.7 +/- 9.2 days. On day 1, the women
      received an oral dose of mifepristone, 600 mg. On day 3, they received an oral
      dose of misoprostol, 400 micrograms, and were monitored for up to 3 hours. If
      they did not expel the conceptus within 3 hours, an additional dose of 200
      micrograms of misoprostol was given and they were monitored for 2 more hours.
      From days 10 to 18, the women were followed up with clinical examination, human
      chorionic gonadotropin measurement, or ultrasound examination. Overall, the
      procedure was successful in 92.9% of women. Efficacy decreased with the duration
      of pregnancy, especially after 56 days of amenorrhea. Up to 42 days of
      amenorrhea, the success rate was 97.6%; between days 42 and 49, 94.8%; between
      days 50 and 56, 93.4%; between days 57 and 63, 86.8%; and after day 63, 83.3%.
      The most common side effects were moderate uterine cramps (80.5%) and
      gastrointestinal (GI) symptoms (34.9%), especially vomiting (18.3%) and diarrhea
      (10.5%). GI symptoms were generally mild. A second dose of misoprostol was given
      to 61.6% of the women. In a subgroup analysis, we assessed the efficacy of 600 mg
      of mifepristone plus 400 or 600 micrograms of misoprostol (one or two doses) in
      women with up to 49 days of amenorrhea and compared it with the efficacy in women
      who received mifepristone plus only 400 micrograms (one dose) of misoprostol in a
      previous study. The overall rate of success (termination of pregnancy) was 95.5%
      in the current study compared with 95.4% in the previous study. The additional
      dose of misoprostol did not significantly increase the overall rate of success,
      but did increase the rate of termination within the monitoring period (69.7%
      versus 64.9% (and within 72 hours after administration of mifepristone (92.7%
      versus 90.4%). We have confirmed that the combination of mifepristone and
      misoprostol was effective, safe, and well tolerated for termination of
      pregnancies at 49 or fewer days of amenorrhea. The efficacy decreased slightly
      between 49 and 56 days, and then decreased significantly between 56 and 63 days.
      For maximal safety and tolerability, we recommend this method only for women with
      49 or fewer days of amenorrhea. A second dose of misoprostol did not improve
      overall efficacy, but did increase the rate of early termination.

PMID- 8574256
TI  - Comparative evaluation of the androgenicity of four low-dose, fixed-combination
      oral contraceptives.
AB  - Changes in endogenous androgen metabolism were compared in healthy women taking
      one of four low-dose modern oral contraceptives (OCs). One hundred women were
      randomized to (1) 35 micrograms ethinyl estradiol (EE) + 250 micrograms
      norgestimate (Cilest); (2) 20 micrograms EE + 150 micrograms desogestrel
      (Mercilon); (3) 30 micrograms EE + 150 micrograms desogestrel (Marvelon); or (4)
      30 micrograms EE + 75 micrograms gestodene (Femodene). During the luteal phase of
      the pretreatment cycle, body weight and blood pressure were recorded, and plasma
      levels of the following variables were recorded: sex-hormone-binding globulin
      (SHBG), cortisol-binding globulin (CBG), testosterone, free testosterone,
      dihydrotestosterone, androstenedione, dihydroepiandrosterone sulfate (DHEAS), and
      hydroxyprogesterone. The free androgen index was also calculated. These variables
      were remeasured during the third week of OC intake and during the fourth and
      sixth cycles. There were no statistically significant differences in androgenic
      variables among the four OCs. The DHEAS concentration decreased less with the 20
      micrograms EE + desogestrel formulation compared with either 30 micrograms EE +
      desogesterel or norgestimate-containing formulations (20% vs. 45%).
      Concentrations of SHBG and CBG increased significantly in all four groups
      (average 263 +/- 119% and 94 +/- 26%, respectively); CBG increased less in women
      taking 20 micrograms EE + desogestrel (about 75%) than in the other formulations
      (about 100%). The four modern, low-dose OCs tested had similar impacts on
      endogenous androgen metabolism, yielding significant decreases in testosterone,
      dihydrotestosterone, androstenedione, and DHEAS. All of these formulations may be
      beneficial in women with androgen-related syndromes such as acne and hirsutism.
      Large studies are under way to establish which of the third-generation OCs is the
      least androgenic. In vitro studies suggest that norgestimate has the least
      androgenic profile.

PMID- 8574257
TI  - Metabolic profile of six oral contraceptives containing norgestimate, gestodene,
      and desogestrel.
AB  - The alterations in lipid metabolism that occur with the use of oral
      contraceptives (OCs) have aroused considerable concern that OCs might increase
      the risk of premature atherosclerosis. However, most studies examining the role
      of OCs in atherogenesis were performed using earlier-generation preparations
      employing larger doses of sex hormones than present formulation. Therefore, we
      undertook a comparative and standardized determination of the effects on lipid
      metabolism of six modern, low-dose OCs. This open, randomized, comparative study
      included patients recruited at 21 study centers throughout Europe. Four hundred
      sixty-six women, aged 18-38 years, participated. They were randomly assigned to
      the following OC formulations:(1) norgestimate 250 micrograms + ethinyl estradiol
      (EE) 35 micrograms (Cilest); (2) norgestimate 180/215/250 micrograms + EE 35
      micrograms (Tricilest); (3) desogestrel 150 micrograms + EE 20 micrograms =
      (Marvelon); (4) desogestrel 150 micrograms + EE 30 micrograms (Mercilon); (5)
      gestodene 75 micrograms + EE 30 micrograms (Femovan); and (6) gestodene 50/70/100
      micrograms + EE 30/40/30 micrograms (Trifemovan). There were three parallel
      studies with six parallel patient groups. Fasting blood samples were drawn at
      baseline (between days 24 and 28) and on days 18-22 of cycle 6, and cycle 12.
      Sample were analyzed for total cholesterol,high-density lipoprotein (HDL)
      cholesterol, HDL2 cholesterol, low-density lipoprotein (LDL) cholesterol,
      triglycerides, apolipoprotein (apo)A1, and apoB at one central laboratory. Two
      hundred eighty-two women completed all 12 cycles and were included in the final
      evaluation. As expected, triglyceride and total cholesterol concentrations
      increased in all study groups but to lesser levels with the formulations
      containing gestodene. All OCs, except the monophasic gestodene preparation,
      slightly but significantly increased HDL. The HDL2 subfraction did ot change
      significantly except in the group using the monophasic gestodene preparation; in
      this group, the HDL2 subfraction slightly but significantly decreased. The LDL
      concentration increased slightly with the monophasic and triphasic norgestimate
      preparations and with desogestrel + 20 micrograms EE. The LDL/HDL ratio did not
      change significantly except with the use of the triphasic norgestimate
      preparation, in which case it decreased slightly. ApoA1 and apoB levels increased
      only slightly with all formulations. Importantly, while all of the OCs tested
      altered lipid levels to some extent, after 12 cycles there were no statistically
      significant differences in lipid effects among OC preparations. Modern, combined
      OCs that contain norgestimate, desogestrel, or gestodene all have some impact on
      lipid levels. However, it would appear likely that they do not contribute to
      atherogenesis in healthy women.

PMID- 8574258
TI  - Support committee for equipment acquisition decisions.

PMID- 8574259
TI  - Third-party and OEM battery performances.

PMID- 8574260
TI  - Health reform and technology--what does it mean for us?
AB  - John Abele, Founder Chairman of Boston Scientific Corporation, spoke at AAMI's
      30th Annual Meeting on 22 May in Anaheim, CA. His speech was part of AAMI's
      plenary session, "The Impact of a Reformed Health System on New Technology."
      After his speech, Abele joined three of AAMI's experts in a roundtable discussion
      on the topics he raised. See the BI&T Forum page 479 for their discussion. As a
      business entrepreneur and scientist, Abele is well versed in the topic of health
      reform and scientific advancements. He began his career with a degree in physics
      and philosophy, then moved into the health care field because of his fascination
      with medical devices and technologies. He has spent years working as an engineer,
      a salesperson, a general manager, and a partner in a research and development
      company. He was a cofounder of AAMI in 1965. Boston Scientific's roots trace back
      to 1969, when Abele joined with Itzhak Bentov to build a company around a
      steerable catheter. The associated technology became a platform for many types of
      tools that could be used as alternatives to surgery in most organs of the body.
      Today, with over 5,000 employees, 4,000 products, and a worldwide presence, the
      original objective of developing products and procedures that reduce risk,
      trauma, cost, and time still applies. Abele is the author of many papers and book
      chapters, and he has lectured extensively on the technology of various medical
      devices and technical, social, economic, and political trends affecting health
      care. His major interests are science education and the process by which new
      technology is invented, developed, and introduced to society. The following
      article is based on Abele's presentation.

PMID- 8574261
TI  - The impact of a reformed health system on new technology. Interview by Bill
      Short.

PMID- 8574262
TI  - The elements of a complete product evaluation.

PMID- 8574263
TI  - Providing fluoroscopy in the CCL during electrical power interruptions.

PMID- 8574264
TI  - Electrostatic discharge interference in the clinical environment. Brief cold
      snaps or humidification disruptions can cause ESD problems.

PMID- 8574265
TI  - A microtensiometer for the analysis of bioadhesive microspheres.
AB  - Bioadhesive polymer microspheres are potential vehicles for the delivery of
      bioactive agents to mucosal tissues. Bioadhesive delivery devices could improve
      drug absorption, enhance bioavailability, and increase patient compliance by
      minimizing dosing regimens. Identification of bioadhesive materials is the first
      phase in developing bioadhesive drug delivery systems. Additionally,
      quantification and analysis of the bioadhesive event are essential to successful
      development of a new generation of adhesive delivery systems. A unique,
      microbalance-based instrument was developed to analyze bioadhesive forces between
      polymer microspheres and mucosal tissue segments. A contact angle analyzer, with
      a custom-made physiologic tissue chamber, was linked to a computer via the serial
      port. Software was used to modify the microbalance operation to behave as a
      microtensiometer with a sensitivity of 0.1 microN. After mounting a microsphere
      and tissue segment in the balance and adjusting the experimental settings, the
      instrument performs a tensile experiment and automatically determines the
      following parameters: compressive deformation, peak compressive load, compressive
      work, yield point, deformation to yield, returned work, peak tensile load,
      deformation to peak tensile load, fracture strength, deformation to failure, and
      tensile work. Using this device the authors identified several bioadhesive
      materials ideally suited for orally-delivered, controlled-release systems. GI
      transit studies in rats showed strong correlation between increased GI-residence
      time and strong bioadhesive interactions.

PMID- 8574266
TI  - The relative safety of gamma-ray, autoclave, and ethylene oxide gas sterilization
      of thermosetting polyurethane.
AB  - Sterilization of polyurethane (PU) produces 4,4'-methylenedianiline (MDA), a
      known carcinogen, and various other compounds. The relationships of the
      components of PU to the formation of these compounds by sterilization were
      studied. Specimens of PU fabricated from different combinations of isocyanates
      and polyols were obtained from dialyzers. The molecular weight of the particular
      polyol was found to influence the production of MDA by sterilization.
      Sterilization also produced many unidentified compounds. MDA production was not
      always associated with the production of the other compounds. Compared with gamma
      ray irradiation and ethylene oxide gas (EOG) sterilization, autoclave
      sterilization eluted more hydrophilic compounds. This phenomenon was significant
      for PUs produced from smaller-molecular-weight polyols. The combination of
      autoclave sterilization and a PU produced from a larger-molecular-weight polyol
      is recommended to minimize the production of potentially toxic compounds. Of the
      techniques studied, EOG sterilization produced the least amounts of MDA and the
      other compounds, but the residue of EOG is itself problematic. The risk posed by
      the amounts of MDA extracted was not significant, but the biological safety of
      the other compounds remains to be determined.

PMID- 8574267
TI  - American registered nurse medical device education: a comparison of simple and
      complex devices.
AB  - Registered nurses (N = 106) working at a 500-bed tertiary care center in a medium
      sized midwestern city on units with high levels of usage of both indwelling
      urethral (Foley) catheters and intravenous infusion pumps were surveyed to
      compare how and what they had learned about the simple compared with the complex
      devices they used in direct patient care, and the consequences of simple vs
      complex device use for both patients and staff nurses. The participants were
      significantly more likely to have learned to use the indwelling urethral catheter
      in nursing school than they were to have learned how to use an intravenous
      infusion pump in nursing school. Staff nurses differed significantly on most (12
      of 17) items about what they had learned and were more likely to have learned
      about various features of the indwelling urethral catheter than about the
      infusion pump. The participants were significantly more likely to feel stressed
      when using an intravenous infusion pump than when using an indwelling urethral
      catheter, but were significantly more likely to have used an indwelling urethral
      catheter that caused a patient harm than an intravenous infusion pump that caused
      a patient harm.

PMID- 8574268
TI  - Human obesity does not segregate with the chromosomal regions of Prader-Willi,
      Bardet-Biedl, Cohen, Borjeson or Wilson-Turner syndromes.
AB  - Prader-Willi, Bardet-Biedl, Cohen, Borjeson and Wilson-Turner syndromes are
      genetic disorders characterized by obesity and other diverse abnormalities. These
      disorders have been mapped to their respective chromosomal regions, and we
      hypothesize that each region contains a gene or genes important in the regulation
      of body weight. We tested this hypothesis by genotyping sibling pairs (n = 207;
      17 markers) from 44 families who were segregating an extreme obesity phenotype
      but were otherwise clinically normal. The number of alleles shared between
      siblings from these chromosomal regions did not correlate with similarity in body
      mass index (kg/m2). If genes in these regions contribute to non-syndromal
      obesity, the prevalence is low and the corresponding alleles are rare.

PMID- 8574270
TI  - Blood pressure, insulin secretion and resistance in nonhypertensive and
      hypertensive obese female subjects.
AB  - OBJECTIVE: To study the relationships between blood pressure, insulin secretion
      and insulin resistance in obese female subjects. DESIGN: Evaluation of insulin
      secretion and resistance respectively by blood C-peptide determination and
      glucose clamp technique in nonhypertensive and hypertensive obese female
      subjects. SETTING: Outpatient clinic of University Hospital. SUBJECTS: 12 female
      obese subjects, six of whom were nonhypertensive, and six hypertensive; and nine
      nonobese nonhypertensive subjects as control. MEASUREMENTS: Baseline and during
      OGTT blood C-peptide as insulin secretion index; M, MCR and M/I ratio evaluated
      by euglycemic hyperinsulinemic clamp as expression of insulin resistance.
      RESULTS: No difference is shown in C-peptide levels, between the two groups of
      obese subjects; the M, MCR and M/I values are significantly lower in hypertensive
      obese vs nonhypertensive obese subjects and controls (P < 0.001). Considering all
      the subjects, the same parameters are significantly inversely correlated with
      mean blood pressure values (P < 0.001). CONCLUSION: In the groups of considered
      obese subjects, homogeneous for age, sex, body weight excess, fat distribution
      and glucose tolerance, blood pressure values are directly related to insulin
      resistance but not to insulin secretion.

PMID- 8574269
TI  - Response of plasma ASP to a prolonged fast.
AB  - OBJECTIVE: To determine the changes in the plasma level of acylation stimulating
      protein (ASP) during a one month total fast in female subjects with marked
      obesity. DESIGN: Patients with marked obesity underwent a month total fast,
      before, during (2 weeks), and at the end of which, a variety of relevant
      metabolic parameters were measured. SETTING: A metabolic unit of a teaching
      hospital. SUBJECTS: 10 women with marked obesity were studied and the results
      compared with those in 16 age-matched controls. MAIN OUTCOME MEASURES: Plasma
      ASP, lipoprotein lipids, apoB, free fatty acid, and ketone levels. RESULTS: At
      baseline, fasting levels of ASP in the obese group were double that in control
      subjects (116 +/- 26 vs 53 +/- 30 nM P < 0.001). During the fast, ASP levels
      dropped progressively and were within the normal range at the end of the study
      (63 +/- 16 vs 53 +/- 30 nM pNS). In addition, there was a strong correlation
      between the plasma ASP at baseline before beginning the fast and the 4 week drop
      in ASP. That is, those subjects who had the highest starting ASP also had the
      largest 4 week drop in ASP (r2 = 0.644, P < 0.005). Of interest, as plasma ASP
      levels dropped, plasma free fatty acid and ketone levels rose and when all
      timepoints were considered, there was a significant inverse relation between
      plasma ASP and plasma free fatty acid (r2 = 0.295, P < 0.0002). CONCLUSIONS: The
      pattern of responses during the fast is that of increasing mobilization of fatty
      acids from adipose tissue coincident with decreased activity of the pathway
      responsible for the storage of adipocyte triglyceride mass. The data are
      consistent, therefore, with the role proposed for ASP as a major determinant of
      the rate of triglyceride synthesis in human adipocytes and thus a potentially
      important factor in the pathophysiology of obesity.

PMID- 8574271
TI  - Oral anabolic steroid treatment, but not parenteral androgen treatment, decreases
      abdominal fat in obese, older men.
AB  - OBJECTIVE: To compare the effects of testosterone enanthate (TE), anabolic
      steroid (AS) or placebo (PL) on regional fat distribution and health risk factors
      in obese middle-aged men undergoing weight loss by dietary means. DESIGN:
      Randomized, double-blind, placebo-controlled clinical trial, carried out for 9
      months with primary assessments at 3 month intervals. Due to adverse blood lipid
      changes, the AS group was switched from oral oxandrolone (ASOX) to parenteral
      nandrolone decaoate (ASND) after the 3 month assessment point. SUBJECTS: Thirty
      healthy, obese men, aged 40-60 years, with serum testosterone (T) levels in the
      low-normal range (2-5 ng/mL). MAIN OUTCOME MEASURES: Abdominal fat distribution
      and thigh muscle volume by CT scan, body composition by dual energy X-ray
      absorptiometry (DEXA), insulin sensitivity by the Minimal Model method, blood
      lipids, blood chemistry, blood pressure, thyroid hormones and urological
      parameters. RESULTS: After 3 months, there was a significantly greater decrease
      in subcutaneous (SQ) abdominal fat in the ASOX group compared to the TE and PL
      groups although body weight changes did not differ by treatment group. There was
      also a tendency for the ASOX group to exhibit greater losses in visceral fat, and
      the absolute level of visceral fat in this group was significantly lower at 3
      months than in the TE and PL groups. There were significant main effects of
      treatment at 3 months on serum T and free T (increased in the TE group and
      decreased in the ASOX group) and on thyroid hormone parameters (T4 and T3 resin
      uptake significantly decreased in the ASOX group compared with the other two
      groups). There was a significant decrease in HDL-C, and increase in LDL-C in the
      ASOX group, which led to their being switched to the parenteral nandrolone
      decanoate (ASND) after 3 months. ASND had opposite effects on visceral fat from
      ASOX, producing a significant increase from 3 to 9 months while continuing to
      decrease SQ abdominal fat. ASND treatment also decreased thigh muscle area, while
      ASOX treatment increased high muscle. ASND reversed the effects of ASOX on
      lipoproteins and thyroid hormones. The previously reported effect of T to
      decrease visceral fat was not observed, in fact, visceral fat in the TE group
      increased slightly from 3 to 9 months, although SQ fat continued to decrease.
      Neither TE nor AS treatment resulted in any change in urologic parameters.
      CONCLUSIONS: Oral oxandrolone decreased SQ abdominal fat more than TE or weight
      loss alone and also tended to produce favorable changes in visceral fat. TE and
      ASND injections given every 2 weeks had similar effects to weight loss alone on
      regional body fat. Most of the beneficial effects observed on metabolic and
      cardiovascular risk factors were due to weight loss per se. These results suggest
      that SQ and visceral abdominal fat can be independently modulated by androgens
      and that at least some anabolic steroids are capable of influencing abdominal
      fat.

PMID- 8574272
TI  - Effects on metabolic rate and fuel selection of a selective beta-3 agonist (ICI
      D7114) in healthy lean men.
AB  - METHOD: ICI D7114 is a selective beta-3 agonist which in some animals increases
      metabolic rate, promotes weight loss and improves glucose tolerance. To
      investigate its potential usefulness in humans, 16 healthy young men (mean age
      28.9 +/- 8.0 years; body mass index 22.5 +/- 1.6 kg/m2) were given ICI D7114 (150
      mg/day, 2.08 +/- 0.24 mg/kg body weight) or placebo for 14 days in a double-blind
      randomised parallel group trial. Energy expenditure (EE) and substrate oxidation
      were assessed by continuous whole-body indirect calorimetry on Day 0 (before
      dosing), on day 1 (acute effect) and on Day 14 (chronic effect). RESULTS:
      Analysis of covariance indicated no significant effects on EE 4 h post-dose (Day
      1, +2.4%, NS; Day 14, +1.0%, NS). There was no chronic effect on either the
      lowest 1 h of sleeping EE (+2.2%, NS) or 24 h EE (+0.7%, NS). There was a
      marginally significant chronic stimulation of basal metabolic rate (+3.6%, P =
      0.042). ICI D7114 had no significant influence on protein, fat or carbohydrate
      oxidation. Tolerability and safety data showed that there were no increases in
      resting heart rate or blood pressure; no change in plasma potassium or reports of
      tremor; no haematological or biochemical abnormalities and no adverse events.
      CONCLUSION: We conclude that over 14 days ICI D7114 at a dose level of 150 mg/day
      has no biologically significant effect on EE in healthy, lean men.

PMID- 8574273
TI  - Relation of waist-hip ratio to glucose tolerance, blood pressure, and serum
      lipids in middle-aged Japanese males.
AB  - OBJECTIVE: To investigate whether waist-hip ratio (WHR) influences glucose
      tolerance, blood pressure, and serum lipids independently of body mass index
      (BMI). DESIGN: Cross-sectional study. SUBJECTS: 2,228 male self-defense officials
      aged 49-55 years in Japan. MEASUREMENTS: BMI, WHR, serum lipids, systolic and
      diastolic blood pressure, and glucose tolerance status according to World Health
      Organization (WHO) criteria. RESULTS: Adjustment was made for smoking, alcohol
      use, physical activity, and inter-hospital variation in statistical analysis.
      Adjusted odds ratios of non-insulin-dependent diabetes mellitus (NIDDM) were
      progressively increased with increasing levels of WHR, but not BMI. Both BMI and
      WHR were independently positively associated with impaired glucose tolerance to
      almost the same degree. Adjusted means of blood pressure, total cholesterol, and
      triglycerides were almost linearly increased with increasing levels of both BMI
      and WHR, and high-density lipoprotein cholesterol was progressively decreased.
      Although the associations of BMI and WHR with blood pressure and serum lipids
      attenuated after mutual adjustment for each, BMI was less influenced by WHR than
      vice versa, except for triglycerides. CONCLUSION: WHR is an important contributor
      not only to NIDDM but also to impaired glucose tolerance, blood pressure, and
      serum lipids, although the associations of WHR with blood pressure and serum
      lipids were generally weaker than those of BMI, except for triglycerides.

PMID- 8574274
TI  - Issues relating to normalization of body fat content in men and women.
AB  - OBJECTIVE: Body mass index (BMI), % body fat, and the fat:lean ratio are ratios
      frequently used as obesity indices. Ratios are based on an assumption that the
      regression between the numerator (e.g. fat mass) and the denominator (e.g. body
      mass) has a zero-intercept. As shown in the companion paper, non-zero intercepts
      cause several problems when ratios are used to adjust data and analysis of
      covariance (ANCOVA) is frequently the preferred statistical tool. The purpose of
      this paper is to examine whether BMI, % body fat and the fat:lean ratio meet the
      necessary criteria for suitable obesity indices using gender comparisons as an
      example. RESULTS: In 720 healthy men and women, BMI was higher in men (24.9 +/-
      3.3 vs 23.4 +/- 3.2 kg/m2, P < 0.001), but fat mass, % fat and the fat:lean ratio
      were higher in women (14.8 +/- 8.4 vs 19.1 +/- 8.1 kg fat; 18.6 +/- 8.7 vs 29.9
      +/- 9.7% body fat; 0.24 +/- 0.14 vs 0.46 +/- 0.20 for the fat:lean ratio; P <
      0.001). Body mass (BM) was correlated with height2 in men (r = 0.40) and women (r
      = 0.36) with equivalent regression slopes (17.1 +/- 1.9 vs 15.6 +/- 2.3 kg per m2
      in women), but the intercepts were different from zero (24.1 kg in men, 20.7 kg
      in women). When BM was adjusted for height2 using ANCOVA, men remained
      significantly heavier than women (74.4 +/- 11.0 vs 68.8 +/- 11.6 kg; P < 0.001).
      Fat mass (FM) was significantly correlated with BM in males (r = 0.64) and
      females (r = 0.78) but the regression slopes were different (0.49 +/- 0.03 vs
      0.71 +/- 0.03 kg of fat per kg body mass in females; P < 0.05) and the intercepts
      were different from zero (-23.2 +/- 2.2 kg in males; -24.8 +/- 2.1 kg in
      females). FM adjusted for BM was significantly higher in women (11.7 vs 25.6 kg).
      FM was inversely correlated with fat free mass (FFM) in males (r = -0.17) and
      females (r = -0.20), with similar regression slopes (-0.16 +/- 0.05 vs -0.26 +/-
      0.08 kg of FM per kg of FFM in women) and the intercepts were significantly
      different from zero (24.8 +/- 3.0 kg in males; 30.7 +/- 3.6 kg in females). When
      FM was adjusted for FFM, there was no significant difference between men (16.3
      kg) and women (17.0 kg). CONCLUSIONS: It is concluded that: (a) the presence of
      significant intercepts does not support the use of ratios as obesity indices and
      regression based models should be considered; and, (b) the direction and
      magnitude of the difference in obesity index between men and women changes with
      different normalization approaches.

PMID- 8574275
TI  - Statistical considerations regarding the use of ratios to adjust data.
AB  - OBJECTIVE: The use of ratios to adjust data (i.e. 'index' variables) is common in
      obesity and related research. The rationale for the use of ratios often seems to
      be the desire to control or eliminate the influence of the variable in the
      denominator. The purpose of this paper is to gain a greater appreciation of the
      statistical assumptions underlying ratios and their impact on data
      interpretation. RESULTS: We demonstrate the limitations of the indiscriminant use
      of ratios to adjust data. Specifically, we show that: (1) given linearity, a zero
      intercept between the numerator and denominator are necessary and sufficient
      conditions for a ratio to remove the confounding effects of the denominator; (2)
      seemingly minor departures from a zero intercept can have major consequences on
      the ratio's ability to control for the denominator; (3) the ratio of two normally
      distributed variables cannot be normally distributed, and this may violate the
      assumptions of subsequent parametric statistical analyses; (4) the use of ratios
      affects the error distribution of the data which may also violate the assumptions
      of subsequent parametric statistical analyses; (5) the use of ratios cannot
      easily take nonlinear effects between the numerator and denominator into account;
      (6) the use of ratios can introduce spurious correlations among the ratios and
      other variables; (7) the use of ratios can create interpretive difficulties. We
      also clarify that the mean of ratios is not necessarily equivalent to the ratio
      of the means of the numerator and denominator. Finally, we present and discuss
      formulae for the reliability of ratios and residuals. CONCLUSION: Because of the
      above issues, we question the indiscriminant use of ratios and advocate that
      investigators consider regression-based approaches as alternatives.

PMID- 8574276
TI  - A randomised placebo-controlled clinical trial of an acupressure device for
      weight loss.
AB  - OBJECTIVE: To provide a randomized placebo-controlled trial to determine the
      efficacy of an auricular acupressure device. DESIGN: Subjects were randomly
      assigned to either treatment or placebo. The treatment group received the
      acupressure device and were instructed to use the device in their dominant ear.
      The placebo group received an acupressure device for their wrist. Participants
      were followed for 12 weeks. SETTING: Outpatient core of the New York Obesity
      Research Center. SUBJECTS: 96 obese adult volunteers, 80 females and 16 males,
      between 19 and 70 years of age. MEASUREMENTS: Weight, body fat, and blood
      pressure measured every two weeks. RESULTS: All subjects combined lost, on
      average, 0.96 kg. There was no significant difference between the two groups on
      weight loss (mean wt loss = 1.28 [s.d. = 2.74] kg for treatment and 0.63 [s.d. =
      3.26] kg for placebo) regardless of whether all subjects were examined or only
      the most compliant subjects were examined. Similarly, there were no significant
      differences between the two groups regarding fat loss or blood pressure
      reduction. CONCLUSION: The acupressure device appears to be a safe device (did
      not cause any harmful side effects). However, it did not promote significantly
      greater weight or fat loss, or declines in blood pressure than placebo.

PMID- 8574277
TI  - Collagen metabolism in obesity: the effect of weight loss.
AB  - OBJECTIVE: To investigate the impact of obesity, fat distribution and weight loss
      on collagen turnover using serum concentrations of the carboxyterminal propeptide
      of type I procollagen (S-PICP) and the aminoterminal propeptide of type III pro
      collagen (S-PIIINP) as markers for collagen turnover. DESIGN: Blood samples were
      obtained once at baseline, and after 8 and 16 weeks of dietary treatment (5.0
      MJ/day diet). SETTING: Outpatient clinic of Hvidovre University Hospital. MAIN
      OUTCOME MEASURES: S-PICP, S-PIIINP, fat distribution and weight loss. RESULTS: S
      PIIINP was associated with body weight (r = 0.37; P = 0.004), height (r = 0.27; P
      = 0.04), waist circumference (r = 0.35; P = 0.007), as well as with WHR (r =
      0.33; P = 0.01) and was inversely correlated to age (r = -0.40; P = 0.002).
      Compared with randomly selected controls from a large pool of healthy volunteers,
      the obese patients had elevated S-PIIINP values before as well as during weight
      loss, whereas S-PICP levels were within the normal range and did not correlate
      with any anthropometric measures. The average weight loss after 16 weeks dietary
      treatment was 8.1 kg (s.d. = 0.8). S-PIIINP decreased during the 16 weeks of
      energy restriction (P < 0.05) and changes in S-PIIINP was correlated to body
      weight loss (r = 0.32; P < 0.05) and to changes in waist circumference (r = 0.34;
      P < 0.05) as well as changes in WHR (r = 0.30; P < 0.05). CONCLUSION: S-PIIINP is
      elevated in obesity and associated with body fat distribution, suggesting an
      increased turnover of type III collagen related to obesity in general and to
      abdominal obesity in particular. S-PIIINP levels decreases during weight loss in
      obese subjects, whereas S-PICP levels seems un-related to obesity and weight
      loss.

PMID- 8574278
TI  - Comparison of the adipoconversion of preadipocytes derived from lean and obese
      Zucker rats in serum-free cultures.
AB  - OBJECTIVE: Serum-free cultures of preadipocytes derived from lean and obese
      Zucker rats were established to compare their adipoconversion in strictly
      controlled culture conditions. DESIGN: Preadipocytes were isolated from the
      epididymal adipose tissue of 4- and/or 8-week-old homozygous lean (Fa/Fa) and
      obese (fa/fa) Zucker rats and cultured in serum-free medium containing insulin,
      transferrin and triidothyronine. MEASUREMENTS: Adipoconversion of lean- and obese
      derived preadipocytes was assessed by morphological observations as well as
      determination of glycerol-3-phosphate dehydrogenase (GPDH) and lipoprotein lipase
      (LPL) activities. RESULTS: In serum-free culture conditions, no significant
      difference was found between lean- and obese-derived cells obtained from 4-week
      old rats. In both groups, an extensive differentiation took place and lipid
      accumulation as well as GPDH activity were similar. By contrast, a differential
      adipoconversion was observed with cells derived from older rats: obese-derived
      cells differentiated poorly, as assessed by the reduced lipid accumulation and
      low GPDH activity. Positive oil red O staining and detection of LPL mRNA and
      activity in obese-derived cultures indicated the preadipose nature of these
      cells. Replacement of insulin by insulin-like growth factor 1 as well as addition
      of glucocorticoids into the serum-free medium did not reduce the difference of
      adipoconversion levels observed between lean and obese cells. CONCLUSION: Taken
      together, these results suggest that the differences in adipoconversion observed
      between preadipocytes derived from lean and obese adult Zucker rats result from
      differences in their stage of commitment to differentiation. The similar
      adipoconversion displayed by preadipocytes derived from younger rats suggests
      that presence of the fa gene does not affect fat storage capacity under serum
      free conditions.

PMID- 8574279
TI  - Daily energy expenditure in free-living conditions in obese and non-obese
      children: comparison of doubly labelled water (2H2(18)O) method and heart-rate
      monitoring.
AB  - OBJECTIVE: To compare the heart-rate monitoring with the doubly labelled water
      (2H2(18)O) method to estimate total daily energy expenditure in obese and non
      obese children. DESIGN: Cross sectional study of obese and normal weight
      children. SUBJECTS: 13 prepubertal children: six obese (4M, 2F, 9.1 +/- 1.5
      years, 47.3 +/- 9.7 kg) and seven non-obese (3M, 4F, 9.3 +/- 0.6 years, 31.8 +/-
      3.2 kg). MEASUREMENTS: Total daily energy expenditure was assessed by means of
      the doubly labelled water method (TEEDLW) and of heart-rate monitoring (TEEHR).
      RESULTS: TEEHR was significantly (P < 0.05) higher than TEEDLW in obese children
      (9.47 +/- 0.84 MJ/d vs 8.99 +/- 0.63 MJ/d) whereas it was not different in non
      obese children (8.43 +/- 2.02 MJ/d vs 8.42 +/- 2.30 MJ/d, P = NS). The difference
      of TEE assessed by HR monitoring in the obese group averaged 6.2 +/- 4.7%. At the
      individual level, the degree of agreement (difference between TEEHR and TEEDLW +/
      2s.d.) was low both in obese (-0.36, 1.32 MJ/d) and in non-obese children (
      1.30, 1.34 MJ/d). At the group level, the agreement between the two methods was
      good in nonobese children (95% c.i. for the bias:-0.59, 0.63 MJ/d) but not in
      obese children (0.04, 0.92 MJ/d). Duration of sleep and energy expenditure during
      resting and physical activity were not significantly different in the two groups.
      Patterns of heart-rate (or derived energy expenditure) during the day-time were
      similar in obese and non-obese children. CONCLUSION: The HR monitoring technique
      provides an estimation of TEE close to that assessed by the DLW method in non
      obese prepubertal children. In comparison with DLW, the HR monitoring method
      yields a greater TEE value in obese children.

PMID- 8574281
TI  - Ventilation and obesity.

PMID- 8574280
TI  - Contribution of beta 3-adrenoceptor activation to ephedrine-induced thermogenesis
      in humans.
AB  - OBJECTIVE: To investigate the contribution of beta 3-adrenoceptor activation to
      sympathetic stimulation of thermogenesis in humans using a sympathomimetic
      (ephedrine) in combination with a non-selective beta-adrenoceptor antagonist
      (nadolol). DESIGN: Three doses (2.5, 5 and 10 mg) of nadolol were used to
      estimate what fraction of the thermogenic response to ephedrine (30 mg) remained
      after inhibition of beta 1- and beta 2-adrenoceptor mediated responses. SUBJECTS:
      Nine healthy, young male volunteers at rest after an overnight fast.
      MEASUREMENTS: Energy expenditure, respiratory quotient, heart rate, blood
      pressure and plasma potassium, glucose, lactate, glycerol, NEFA and triglycerides
      were measured before, and for 3 h after treatment with placebo, ephedrine and
      ephedrine plus three doses of nadolol. RESULTS: Ephedrine produced significant
      increases in energy expenditure (thermogenesis), heart rate, systolic blood
      pressure and plasma glucose; the other parameters measured did not change
      significantly. Nadolol caused significant inhibition of all responses, but 43% of
      the thermogenic response to ephedrine remained after the 2.5 mg dose of nadolol,
      whereas the same dose completely inhibited the heart rate and plasma glucose
      responses. CONCLUSION: All three beta-adrenoceptor subtypes (beta 1, beta 2 and
      beta 3) may be involved in ephedrine-induced thermogenesis, but the resistance to
      complete inhibition by the non-selective antagonist nadolol indicates that at
      least 40% of the response is mediated by an atypical receptor, which is presumed
      to be the beta 3-adrenoceptor.

PMID- 8574282
TI  - TSH receptor and LH receptor, 1995.

PMID- 8574283
TI  - Molecular Endocrinology of the oxytocin receptor.

PMID- 8574284
TI  - Molecular studies on thyrotropin (TSH) receptor and anti-TSH receptor antibodies.
AB  - Cloning of TSHR gene and some subsequent studies using the gene were described.
      Enormous numbers of studies have been performed since the cloning of TSHR gene.
      Recent molecular studies on TSH receptor and TSHRAb gave various impacts on
      thyroidology and are resolving past problems. We mainly focused on regulation,
      processing and glycosylation, TSH- and TSHRAb binding sites, T cell epitopes, and
      signal transduction of TSHR. Furthermore, we isolated and characterized TSHRAb
      genes using lymphocytes producing monoclonal TSHRAb obtained from patients with
      Graves' disease and primary hypothyroidism. Thus, both antigen and antibody genes
      are cloned. Combined use of these genes will help to investigate the interactions
      between TSHR and TSHRAb, and may be expected to contribute to the understanding
      of molecular mechanisms underlying the pathogenesis of autoimmune thyroid disease
      as well as the physiology of the thyroid gland.

PMID- 8574285
TI  - Differences in down-regulation of glucocorticoid receptor mRNA by cortisol,
      prednisolone and dexamethasone in HeLa cells.
AB  - Glucocorticoids regulate the levels of their cognate receptors in a number of
      target tissues and in many different cell lines. We have compared the effect of
      three glucocorticoids, cortisol and its synthetic derivatives, prednisolone an
      dexamethasone, on the levels of glucocorticoid receptor (GR) mRNA in HeLa cells.
      Clinically, the synthetic derivatives are more active in hormonal action and have
      a longer half-life than cortisol. In the present study, the amounts of GR mRNA in
      HeLa cells were examined by Northern blot hybridization after treatment with
      cortisol, prednisolone or dexamethasone. These glucocorticoids decreased GR mRNA
      levels differently. After 24 h treatment with 1 x 10(-5) M cortisol, GR mRNA
      levels were only marginally suppressed (90% of the control), while prednisolone
      and dexamethasone suppressed GR mRNA levels to 67 and 57%, respectively. These
      differences may relate to the biological activities of these glucocorticoids. In
      time course studies, GR mRNA levels of the cells treated with cortisol and
      prednisolone decreased to the minimum levels within 4 h and then recovered
      gradually, while those treated with dexamethasone reached the minimum level at 8
      h and remained suppressed for more than 24 h. These differences may relate to the
      biological half-lives of these glucocorticoids.

PMID- 8574286
TI  - A case of deoxycorticosterone-producing adrenal adenoma.
AB  - A 29-year-old woman with deoxycorticosterone (DOC)-producing adrenocortical
      adenoma had hypertension and hypokalemia but without Cushingoid features. Plasma
      renin activity and the aldosterone concentration were low, while the DOC
      concentration was high (6.10-10.3 ng/ml; normal range 0.03-0.33). Plasma
      cortisol, androgens, and estrogens as well as urinary 17-OHCS and 17-KS were
      within normal limits. Furosemide administration and two hours upright posture
      resulted in a 3-fold increase in plasma DOC, but the administration of ACTH,
      dexamethasone, or angiotensin III had no effect on plasma DOC. Following
      resection of a right adrenal tumor weighing 70 g, the hypertension and
      hypokalemia disappeared. DOC content in the tumor was high. On light microscopic
      examination, the tumor was encapsulated, composed of cells with clear cytoplasm
      and large nuclei and there were extensive areas of fibrosis and infiltration of
      lymphocytes. According to Weiss's criteria, the tumor was considered to be an
      adrenocortical adenoma. Immunohistochemically, P450scc, 3 beta HSD, P450C21 and
      P45011 beta were positive with heterogeneity of intra-tumoral expression. No
      immunoreactivity for P45017 alpha in this adenoma was detected. This is different
      from a previous report in which a relatively small number of cells in DOC
      secreting adrenocortical carcinoma were positive for P45017 alpha.

PMID- 8574287
TI  - Premature termination mutation (772Glu-->stop) in the hormone-binding domain of
      the androgen receptor in a patient with the receptor-negative form of complete
      androgen insensitivity syndrome.
AB  - We have characterized the androgen receptor in a Japanese infant with complete
      androgen insensitivity syndrome (or androgen resistance), and have investigated
      the molecular basis. Androgen binding was undetectable in cultured genital skin
      fibroblasts from this patient by whole-cell androgen receptor binding assay.
      Sequence analysis of the entire coding region of the androgen receptor gene from
      this patient revealed a single nucleotide substitution (G-->T) at nucleotide
      position 2676 in exon E (or 5), resulting in conversion of glutamine codon (GAG)
      to amber stop codon (TAG) at amino acid position 772 within the hormone-binding
      domain of the androgen receptor. This premature termination mutation (or nonsense
      mutation), introducing a truncated androgen receptor that lacks most of its
      androgen binding capacity, is though to cause the receptor-negative form of
      complete androgen insensitivity syndrome in this patient.

PMID- 8574288
TI  - Increased expression of a regenerating (reg) gene protein in neonatal rat
      pancreas treated with streptozotocin.
AB  - We examined the expression of reg protein in neonatal rat pancreas treated with
      streptozotocin (STZ) by means of the immunohistochemical technique and northern
      blotting. Seven days after STZ injection, the plasma glucose levels in STZ
      treated neonatal rats were significantly higher than those in control rats.
      Scattered distribution of reg protein in pancreatic islet cells was clearly
      observed in STZ-treated rats, but not in control rats. On the other hand, reg
      proteins was positively stained in the exocrine cells in both groups of rats.
      Northern blot analyses revealed that the expression of insulin mRNA markedly
      decreased in STZ-treated rat pancreas, but a significant increase in reg mRNA
      expression was recognized in the STZ-treated rat pancreas compared with that of
      control rats. Rats treated with STZ during the neonatal period have been used as
      a model of non-insulin-dependent diabetes mellitus (NIDDM) and beta cell
      regeneration. Thus, the increased reg gene expression in neonatal STZ-treated rat
      pancreas was therefore described for the first time, and thus would be a useful
      model for studying the relationship between NIDDM and beta cell regeneration or
      reg gene protein.

PMID- 8574289
TI  - A rare case of primary pulmonary choriocarcinoma in a male: immunohistochemical
      detection for human chorionic gonadotropin, epidermal growth factor (EGF) and EGF
      receptor.
AB  - a rare case of primary choriocarcinoma of the lung in a male is described with
      immunohistochemistry for human chorionic gonadotropin (hCG), epidermal growth
      factor (EGF) and EGF-receptor. The extragonadal trophoblastic origin of this
      pulmonary carcinoma was definitely confirmed by an autopsy examination, and hCG
      production and hCG-positive staining of the tumor cells. Furthermore, the tumor
      cells clearly expressed EGF and its receptor which play an important role in the
      proliferation and differentiation of normal and neoplastic trophoblasts of the
      uterus. Our present case suggests that EGF may act in an autocrine manner in the
      tumor cells of primary pulmonary choriocarcinoma.

PMID- 8574290
TI  - Long-term effects of thyroid hormone on lymphocyte subsets in spleens and
      thymuses of mice.
AB  - We examined the effects of the long-term administration to mice of thyroid
      hormone or propylthiouracil (PTU) on lymphocyte subsets in spleens, and thymuses
      to clarify whether hyperthyroxinemia itself causes the changes in lymphocyte
      subsets, such as the marked increase in CD5+ B cells and decrease in natural
      killer (NK) cells, observed in hyperthyroid Graves' disease. Both the number and
      proportion of splenic NK (Thy-1+ asialo GM1+) cells were increased in
      hyperthyroxinemic mice treated with thyroxine (T4) for both short and long terms
      (8 and 32 weeks, respectively), those of splenic and thymic T (CD5+ sIgM-) cells
      and CD5-B cells were increased only in hypothyroxinemic mice treated with PTU for
      32 weeks, compared with those in euthyroid mice. These data indicate that 1) long
      term hyperthyroxinemia increases splenic and thymic T cells and splenic NK cells,
      but not CD5+ B cells, in mice, 2) long-term hypothyroxinemia induced by PTU
      treatment increases splenic B cells and CD5- B cells, and 3) hyperthyroxinemia
      itself does not cause the changes in CD5+ B cells and NK cells, which are
      observed in hyperthyroid Graves' disease, in mice.

PMID- 8574291
TI  - Effect of alpha 2-adrenergic agonist clonidine on plasma growth hormone and
      insulin-like growth factor-I concentrations in barrows.
AB  - The effects of infusion of clonidine, an alpha2-adrenergic agonist, on plasma
      insulin-like growth factor-I (IGF-I) concentrations were investigated with a
      single growth hormone (GH) injection in pigs. Four barrows were subjected to four
      treatments: saline infusion with a vehicle injection, clonidine infusion (0.5
      nmol/kg/min for 8 h) with a vehicle injection, saline infusion with a bovine GH
      (bGH: 100 micrograms/kg) injection, and clonidine infusion with a bGH injection.
      Infusion was started 1 h before the injection. Plasma IGF-I, bGH, porcine GH
      (pGH), insulin, glucose, non-esterified fatty acid (NEFA), and blood urea
      nitrogen (BUN) concentrations were measured. Plasma IGF-I concentrations during
      saline infusion increased after a bGH injection (P < 0.05). However, the IGF-I
      concentrations during clonidine infusion did not increase after the bGH
      injection. Plasma endogenous GH (pGH) was not increased during clonidine
      infusion. The plasma glucose concentration was noticeably increased during
      clonidine infusion and moderately increased after the GH injection. Despite the
      extreme increase in plasma glucose during clonidine infusion, plasma insulin did
      not change. Neither plasma NEFA nor BUN was changed by these treatments. These
      results demonstrate that the alpha 2-adrenergic agonist clonidine altered the
      action of GH to increase the plasma IGF-I concentrations.

PMID- 8574292
TI  - 17 alpha-Hydroxyprogesterone suppresses neovascularization induced by HPLC
      purified ovarian hyaluronic acid-like glycosaminoglycan in mice.
AB  - HPLC-purified glycosaminoglycans (hpGAG) prepared from extracts of non-luteal
      mouse (JcL:ICR strain) ovaries were assayed for neovascularization by implanting
      Elvax films, containing test samples, on the lateral wall of the sheath of m.
      rectus abdominis in adult female mice of the same strain. Neovascularization
      occurred in a dose-dependent manner, and was characterized by capillary outgrowth
      extending into the tissue surrounding the implant. The single major peak of
      purified GAG on a column of TSK gel DEAE got out of order after treatment with
      streptococcal hyaluronidase or nitrous acid. The activity of this fraction was
      also greatly reduced when treated with streptococcal hyaluronidase or nitrous
      acid. When hpGAG was embedded in the implant with 17 alpha-hydroxyprogesterone at
      a dose of 20 micrograms/film, neovascularization induced by means of hpGAGs was
      suppressed. Progesterone at a dose of 50 micrograms/film did not suppress the
      neovascularization induced by ovarian hpGAG. These findings suggest that 17 alpha
      hydroxyprogesterone suppresses the angiogenic activity of hyaluronic acid-like
      hpGAG in the ovary.

PMID- 8574293
TI  - Acute spontaneous hemorrhagic degeneration of the thyroid nodule with subacute
      thyroiditis-like symptoms and laboratory findings.
AB  - Seventeen consecutive patients (3 men and 14 women, aged 14-75 years) with a
      hemorrhagic degeneration of the thyroid nodule, which was confirmed by both
      ultrasonography and either reddish or brown fluid evacuated by fine-needle
      aspiration, were classified as either acute type with an episode of abrupt
      painful swelling of the thyroid (n = 4), or chronic type in which a painless
      thyroid nodule was incidentally found (n = 13). One of the four acute type
      patients demonstrated subacute thyroiditis-like symptoms and laboratory findings
      including transient painful thyrotoxicosis associated with high serum levels of
      thyroid hormones and thyroglobulin (Tg), a suppressed serum TSH level, a low
      thyroidal radioactive iodine uptake (RAIU), and accelerated erythrocyte
      sedimentation rate (ESR). In the other three acute type patients the serum level
      of Tg increased markedly, the serum thyroid hormones level increased in one, the
      thyroidal RAIU was low in two, and the ESR was accelerated in one. In the
      thirteen chronic type patients, the serum levels of the thyroid hormones and the
      thyroidal RAIU were within the normal range, and few inflammatory signs were
      observed. These findings suggest that acute hemorrhagic degeneration of the
      thyroid nodule may thus cause transient subacute thyroiditis-like symptoms and
      laboratory findings.

PMID- 8574294
TI  - Effect of lithium on serum calcium level and parathyroid function in manic
      depressive patients.
AB  - The purpose of this study is to find out whether hypercalcemia and
      hyperparathyroidism are rare or not in manic-depressive patients taking lithium
      carbonate. The subjects were 13 patients receiving lithium and 19 healthy
      subjects not receiving it as normal controls. Serum ionized calcium (Ca++), serum
      parathyroid hormone (PTH), urinary calcium and cyclic AMP(cAMP) were measured.
      Cervical ultrasonographic examination was also performed. The mean serum Ca++
      level in the lithium administered group was significantly higher than that in the
      control group (P < 0.02). There was no significant difference between the serum
      PTH levels in the two groups. The mean urinary calcium level in the lithium
      administered group was below the normal range, but the mean urinary of cAMP level
      was within the normal range. Although a parathyroid cyst was found in one lithium
      administered patient on ultrasonographic examination, no swelling of the
      parathyroid gland was observed in the other patients in the lithium administered
      group or in any of the control subjects. In the present study, no distinct
      hyperparathyroidism was found in the patients in the lithium administered group.
      Lithium administration affects calcium metabolism in manic-depressive patients
      and hypercalcemia seems to be one of the complications needing attention at the
      time of lithium administration.

PMID- 8574295
TI  - A hyperthyroid patient with Graves' disease who was strongly resistant to
      methimazole: investigation on possible mechanisms of the resistance.
AB  - We treated a patient who was hyperthyroid due to Graves' disease and strongly
      resistant to methimazole (MMI): in spite of good compliance, she needed 150 mg of
      MMI daily to control her hyperthyroidism. To elucidate the reasons of resistance
      to MMI, her serum and intrathyroidal MMI concentrations were determined by high
      pressure liquid chromatography (HPLC). After taking a 30 mg dose of MMI, she had
      a similar serum MMI concentration-time curve to that of a normal subject: drug
      malabsorption and rapid drug metabolism were not evident when studied after
      surgical treatment. After her serum containing MMI was incubated with Protein G,
      the MMI concentration of the fraction not bound to Protein G did not change
      significantly from that of untreated serum: the possibility of anti-MMI IgG
      antibody production was considered unlikely. Furthermore, the intrathyroidal
      concentration of MMI in a surgically obtained tissue specimen was 3 micrograms/g
      wet tissue and appeared to be comparable with those of other Graves' tissues
      reported. Considering that the patient had been taking 150 mg per day of MMI by
      the time of thyroidectomy, her intrathyroidal MMI concentration was relatively
      low, suggesting possible impairment of intrathyroidal MMI accumulation. The
      possibilities of impaired intrathyroidal actions and the severity of
      hyperthyroidism, especially high T3 levels, also remained as possible causes. In
      conclusion, here was a severely hyperthyroid patient who was poorly responsive to
      conventional doses of MMI, and impairment of thyroid uptake of MMI or of pathways
      after uptake were considered as possible mechanisms.

PMID- 8574296
TI  - Effects of ethanol treatment on Leydig cellular NADPH-generating enzymes and
      lipid profiles.
AB  - Effects of ethanol treatment on Leydig cell NADPH-generating enzymes and lipid
      profiles were studied. Ethanol treatment (3.0 g/kg b.wt.) twice daily as a 25%
      (v/v) aqueous solution given to adult Wistar rats reduced the body weight, testis
      weight and relative weights of the seminal vesicles and ventral prostate. Serum
      LH and testosterone were also decreased. Similarly, the NADPH-generating enzymes
      such as G-6-PDH, 6-PGDH, NADP-ICDH were reduced, but malic enzyme was unaltered.
      Leydig cell total lipid was decreased: neutral lipids such as esterified
      cholesterol and triacyl glycerol were decreased but free cholesterol and diacyl
      glycerol were increased. The reduction in total phospholipid was contributed to
      by fractions such as phosphatidyl inositol, phosphatidyl serine, phosphatidyl
      choline and phosphatidyl ethanolamine. Withdrawal of ethanol treatment for 30
      days restored these to the normal level. The present findings suggest that the
      ethanol treatment impairs Leydig cellular NADPH generation which may be one of
      the biochemical mechanisms mediating the direct and indirect effects of ethanol
      resulting in hypoandrogenization.

PMID- 8574297
TI  - The prevalence of thyroid dysfunction among elderly subjects in an endemic goiter
      area of Central Anatolia.
AB  - The prevalence of thyroid dysfunction in the elderly is reported to be markedly
      high, at least in some Western countries in which iodine intake is sufficient or
      increased because of recent supplementation of iodine for public health. We
      therefore wished to investigate the prevalence of thyroid dysfunction among
      elderly people in an endemic goiter area. The study included 198 subjects over
      the age of 55 years. It was carried out in two towns 20-30 km, south of Kayseri,
      Central Anatolia. Questioning on medical history, physical examination and
      grading of thyroid gland size were performed. Serum TSH was measured by a
      sensitive immunoradiometric assay. Serum free thyroid hormones and thyroid
      autoantibodies were measured in the subjects with TSH concentrations below 0.4 mu
      IU/ml or above 4.5 mu IU/ml on the initial screen. Drinking water was also
      analysed for iodine content. Twenty-five (12.6%) subjects had either elevated
      (6.5%) or suppressed (6.1%) serum TSH levels. No patient had clinical
      hypothyroidism (high TSH and low free thyroxine and free triiodothyronine). Three
      (1.5%) subjects had clinical hyperthyroidism (low TSH and high free thyroxine and
      free triiodothyronine). Only one subject was positive for antimicrosomal and
      antithyroglobulin antibodies. The prevalence of goiter was 25.8%. The iodine
      level in drinking water was found to be 3 micrograms/L. In conclusion, we believe
      that the prevalence of thyroid dysfunction in the elderly may depend on the
      iodine status in the environment. We think that hyperthyroidism due to
      multinodular goiter is more important than hypothyroidism for elderly people
      living in an endemic goiter area, probably due to the low frequency of autoimmune
      thyroid disorders.

PMID- 8574298
TI  - The interactive effects of VIP, PHI, GHRH, and SRIF on the release of growth
      hormone from cultured adenohypophysial cells in cattle.
AB  - The effects of hypothalamic peptides [vasoactive intestinal peptide (VIP),
      peptide histidine isoleucine (PHI), growth hormone (GH)-releasing hormone (GHRH)
      and somatostatin (SRIF) on GH release from cultured bovine adenohypophysial cells
      were studied. The cells were incubated for 2 h with the peptides after
      preincubation for 3.5 days. At doses from 10(-9) to 10(-7)M VIP, the amount of GH
      released was significantly greater than in the controls (P < 0.05 to P < 0.001).
      PHI (10(-10 to 10(-7)M did not alter the bovine GH concentration in the media.
      Incubation with the media containing 10(-7)M GHRH, 10(-7)M VIP, and combined
      treatment with the VIP plus GHRH increased GH by 186, 40 and 182%, respectively
      (P < 0.001). Furthermore, although VIP-induced GH release was significantly
      decreased by SRIF compared with the treatment with VIP alone (P<0.001), the VIP
      significantly blunted the inhibitory effect of the SRIF on GH release by 24% when
      compared with that of the SRIF plus GHRH without the VIP (P < 0.05). GH release
      in combined treatments with VIP, GHRH and SRIF was significantly less than that
      of the VIP plus GHRH (P < 0.001), but it was significant 29% increase compared
      with the SRIF plus GHRH (P < 0.05). The combined effects of the VIP (10(-7)M)
      with GHRH (10(-7), 10(-8) and 10(-10)M significantly induced GH release compared
      with the controls (P < 0.001), but no additive effect was not observed when
      compared with the GHRH alone. The results indicate that VIP, but not PHI, acts
      directly on cultured adenohypophysial cells to induce GH release in cattle.

PMID- 8574299
TI  - c-Kit proto-oncogene is more likely to lose expression in differentiated thyroid
      carcinoma than three thyroid-specific genes: thyroid peroxidase, thyroglobulin,
      and thyroid stimulating hormone receptor.
AB  - Although c-kit proto-oncogene product is known to be weakly expressed on normal
      thyrocytes, its function is unclear. In order to investigate the significance of
      thyroid c-kit, c-kit gene expression in 37 various thyroid tissues was analyzed
      by comparing c-kit gene expression with the mRNA expression of three thyroid
      specific genes: thyroid peroxidase, thyroglobulin, and thyroid stimulating
      hormone receptor, c-kit mRNA was hardly detected by the usual northern blot
      method in 2 of 7 follicular carcinomas, 11 of 12 papillary carcinomas, and a
      medullary carcinoma. On the other hand, a high level of c-kit mRNA expression was
      found in all 17 benign thyroid tissues (4 normal thyroid tissues, 4 Graves'
      disease, 2 adenomatous goiters, and 7 follicular adenomas). This study found that
      c-kit proto-oncogene is more likely to lose expression in differentiated thyroid
      carcinoma than any thyroid-specific gene. Decreased c-kit gene expression may
      serve as an indicator for the de-differentiation of thyrocytes.

PMID- 8574300
TI  - Influence of body position on breathing and its implications for the evaluation
      and treatment of speech and voice disorders.
AB  - This paper examines how breathing differs in the upright and supine body
      positions. Passive and active forces and associated chest wall motions are
      described for resting tidal breathing and speech breathing performed in the two
      positions. Clinical implications are offered regarding evaluation and treatment
      of breathing behavior in clients with speech and voice disorders.

PMID- 8574301
TI  - Frequency and risk factors for voice problems in teachers of singing and control
      subjects.
AB  - Using a questionnaire format, 125 teachers of singing and 49 control subjects
      indicated whether they had a current or past voice problem, and provided
      information about their demographic characteristics, voice use patterns, and
      medication use. The results revealed similar rates of current voice problems
      reported by the two subject groups. However, teachers of singing were
      considerably more likely to report ever having had a voice problem than controls
      (64 vs. 33%). Risk factors were similar for the two groups. Dehydrating
      medications and a report of a past voice problem both increased the likelihood of
      perceiving a current problem, by a factor of three and five, respectively.
      Females were twice as likely to report a past voice problem as males, and younger
      subjects were slightly more likely to report a past problem as compared with
      older subjects. The implications of the findings are discussed from a theoretical
      as well as pragmatic perspective.

PMID- 8574302
TI  - Differences in phonetogram features between male and female subjects with and
      without vocal training.
AB  - Singing not only requires good voluntary control over phonation and a musical
      ear, it also demands certain capacities of the voice source. These capacities
      include a desirable range of sound intensity and frequency, which can be measured
      and represented in a phonetogram. The influence of specific factors on voice
      capacities may be ascertained by the analysis of phonetograms. To determine the
      influence of the factors gender and voice training, phonetograms of 224 subjects,
      subdivided accordingly into four groups, were analyzed in two different ways. One
      is based on the rescaling of phonetograms, whereas the other derives analytic
      variables from the features' shape, area, and dynamic range. Analysis showed
      that, regarding gender, male subjects are able to produce softer phonations,
      whereas female subjects produced louder phonations at specific parts of their
      comparable frequency ranges. Trained subjects have a larger enclosed area of the
      phonetogram, which is primarily based on extended soft voice capabilities in both
      genders and the significantly larger frequency range in trained female subjects.
      The shape analysis, performed with Fourier Descriptors, revealed differences for
      the factors gender and training.

PMID- 8574303
TI  - Comparisons of jitter, shimmer, and signal-to-noise ratio from directly digitized
      versus taped voice samples.
AB  - The purpose of this study was to compare jitter, shimmer, and signal-to-noise
      ratio (SNR) measures obtained from tape-recorded samples with the same measures
      made on directly digitized voice samples, with use of the CSpeech acoustic
      analysis program. Subjects included 30 young women who phonated the vowel /a/ at
      a comfortable pitch and loudness level. Voice samples were simultaneously
      recorded and digitized, and the resulting perturbation measures for the two
      conditions were compared. Results indicated that there were small but
      statistically significant differences between percent jitter, percent shimmer,
      and SNR calculated from taped samples compared with the same measures calculated
      from directly digitized samples. It was concluded that direct digitization for
      clinical measures of vocal perturbation was most desirable, but that taped
      samples could be used, if necessary, with some caution.

PMID- 8574304
TI  - Comparison of fundamental frequency and perturbation measurements among three
      analysis systems.
AB  - The need for standardization of procedures in approaches to voice measurement has
      been recently emphasized. The purpose of this study was to determine the extent
      to which the acoustic perturbation measurements from three different analysis
      systems agree when standardized recording and analysis procedures are used. High
      quality acoustic voice recordings from 20 patients were analyzed. The results
      showed that, although fundamental frequency measurements were in strong agreement
      among the three systems tested, frequency and amplitude perturbation measurements
      were not in agreement. The underlying approaches to perturbation measurement
      appeared to be sufficiently different to produce different results. An argument
      is made for a standardized set of acoustic signals representing normal,
      dysphonic, and synthesized voices with known characteristics to facilitate
      testing of new acoustic analysis systems and confirm measurement accuracy and
      sensitivity.

PMID- 8574305
TI  - Reliability of pitch discrimination of vowel and piano tones.
AB  - This study evaluated the reliability of pitch judgments as a basic step toward
      increasing interrater and intrarater reliability of multidimensional perceptual
      judgments of the speaking voice. Forty-five undergraduate university students
      studying speech/language pathology made piano-to-piano tone pitch matches and
      vowel-to-piano pitch matches using a computer software program. The mean
      percentage correct of piano-to-piano tone matches was 91.3% and of vowel-to-piano
      matches was 75.6%. Subjects who scored 100% correct were significantly faster at
      the pitch matching task. Further research of perceptual judgments of pitch and
      its contribution to multidimensional rating tasks is warranted.

PMID- 8574306
TI  - Fundamental frequency and tracheal pressure during three types of vocalizations
      elicited from anesthetized dogs.
AB  - Electrical stimulation of the midbrain was used to elicit a variety of
      vocalizations from six anesthetized dogs. This study was conducted to investigate
      the ranges of and relationships between fundamental frequency of the
      vocalizations (F0) and tracheal pressure (Pt) produced during the vocalizations.
      The vocalizations were described according to type (growl, howl, and whine); F0
      and Pt, as well as patterns of laryngeal muscle activity, were examined for each
      vocalization type. Natural-sounding growl and howl vocalizations were elicited
      from five dogs; three dogs also produced whines. With few exceptions, F0 was
      categorically different for the three vocalization types (low for growls, average
      for howls, very high for whines). Pt values overlapped for the three vocalization
      types, although, on average, howls were produced with greater Pt than growls.
      Patterns and degrees of laryngeal muscle activity varied across and within
      vocalization types, but general findings were consistent with the presumed
      function of most of the muscles. Laryngeal muscle activity may help explain some
      of the variability in the acoustic and aerodynamic data.

PMID- 8574307
TI  - Speech task effects on acoustic and aerodynamic measures of women with vocal
      nodules.
AB  - Vowel prolongation is often used to evaluate disordered voice production. In
      light of previous findings showing that co-articulation has significant influence
      on laryngeal function measures, the practice of using prolonged vowels to
      represent a speech sample is questioned. To test whether disordered and normal
      voice during vowel production is generalizable to connected speech, three
      speaking tasks were investigated: sustained vowel prolongation, syllable
      repetition and reading. Statistical differences were found between these tasks
      for certain amplitude and time based laryngeal function measures for adult women
      with disordered and normal voice. However, for the specific measures which were
      statistically different, the actual numerical and perceptual differences may be
      quite small. From a clinical assessment standpoint, the choice of the speech task
      may not make an apparent difference in the objective evaluation of disordered
      voice.

PMID- 8574308
TI  - Effects of practice with and without knowledge of results on jitter and shimmer
      levels in normally speaking women.
AB  - The effects of practice on jitter and shimmer were assessed in two groups of
      normally speaking women. Subjects in both groups sustained trials of /a/ as
      steadily as possible during a baseline session, two practice sessions, and a
      transfer session. Subjects in one group received visual and verbal feedback
      during the practice sessions. Subjects in the other group received no feedback.
      Shimmer means remained essentially stable over the four sessions for both groups,
      and no differences were apparent between the groups. Jitter values were
      significantly different between sessions for both groups, and between the two
      groups for the practice sessions. These results are consistent with findings from
      manual performance and retention tasks. The present findings also support a
      recently developed neurologic model of jitter.

PMID- 8574309
TI  - The effects of intraoral pressure change on F0 regulation--preliminary study for
      the evaluation of vocal fold stiffness.
AB  - This study was intended to evaluate the stiffness of the vocal folds
      noninvasively. As a first step, the relationship between vocal fundamental
      frequency (F0) and intraoral pressure (P0) was investigated. F0 was recorded
      during production of forced P0 changes in three men and four women while they
      uttered sustained vowels. The pressure changes were applied by closing a valve
      mounted on a mouthpiece. Changes in F0 as a function of changes in P0 (dF0/dP0)
      were then measured. The values of dF0/dP0 varied with F0 in a manner inherent to
      each subject. The relationship between dF0/dP0 and F0 was found to have a
      potential benefit for the evaluation of stiffness at a specific length of vocal
      fold.

PMID- 8574310
TI  - Measures of vocal function during changes in vocal effort level.
AB  - The purpose of this article is to present the results of a controlled study of
      the day-to-day variabilities of three acoustic parameters (jitter, shimmer, and
      normalized noise energy), and two electroglottographic parameters (contact
      quotient and contact quotient perturbation) for vowels produced at three vocal
      efforts (low, normal, high). Data were obtained with use of a sophisticated
      bilinear interpolation pitch detection method. A repeated measures design
      required subjects to produce the vowels /ae/ and /a/ five times a day over 3 days
      at each vocal effort level. The jitter, shimmer, and normalized noise energy
      values from acoustic measures and contact quotient and contact quotient
      perturbation values varied significantly among the three vocal effort levels. The
      clinical implication of this finding is that vocal effort must be controlled in
      order to obtain consistent clinical measures. Furthermore, day-to-day variability
      must be taken into account if representative measures are to be obtained for
      clinical use.

PMID- 8574311
TI  - "Compensatory falsetto": effects on vocal quality.
AB  - The term "compensatory falsetto", for the purpose of this investigation, refers
      to the development of an abnormally high-pitched voice in the presence of
      laryngeal pathology where more socially acceptable lower pitched voice production
      is possible. The purpose of this investigation was to compare laryngeal
      compensations and their effects on objective measures of vocal function during
      production of compensatory falsetto voice. Eighteen patients with abnormally high
      pitched voice in the presence of underlying laryngeal pathology were evaluated in
      the Department of Otolaryngology at the University of Miami School of Medicine
      from January, 1988 through December, 1992 and were diagnosed with "compensatory
      falsetto". Vocal fold paralysis (n = 11) was the most common laryngeal pathology.
      Vibratory characteristics were evaluated through videostrobolaryngoscopic
      examination. Acoustic and aerodynamic parameters assessed included fundamental
      frequency, jitter rate, harmonic-to-noise ratio, glottal air flow, and maximum
      phonation time. Production of a higher-pitched voice appeared to improve glottic
      closure and decrease the amount of air loss during phonation. A corresponding
      increase in maximum phonation time and improvement in acoustic characteristics of
      jitter and harmonic-to-noise ratio was also observed.

PMID- 8574312
TI  - Effects of chronic ozone (O3) exposure on vocal-fold mucosa in bonnet monkeys.
AB  - Effects of ambient ozone (O3) on the respiratory tract have been frequently
      reported. However, little is known regarding possible effects of chronic exposure
      to O3 on the larynx or on vocal-fold mucosa. In this study, six bonnet monkeys
      were exposed to 1 ppm O3 8 h per day, 5 days per week, for 3 months. Three of the
      monkeys' larynges were examined 4 h after exposure, and three were examined 9
      months after exposure. Tissues were subjected to histological staining and
      morphometric quantification. Results revealed increased thickness of epithelial
      and connective tissue components of vocal-fold mucosa in the 4-h group and
      connective tissue changes that persisted in mucosa examined 9 months after
      exposure. Additional changes indicative of hyperplasia and disorganization of
      epithelial and connective tissue, as well as disruption of glands and vessels,
      were also noted in tissues examined at both postexposure intervals. Implications
      of the data for the larynx and voice quality in humans exposed to similar
      environmental toxins are discussed.

PMID- 8574313
TI  - Sociodemographic variables of a German sample of patients with contact granuloma.
AB  - We report 28 German patients with contact granuloma (27 male, 1 female). Their
      mean age was 52 years (ranging from 35 to 70). Thirty-two percent were retired.
      The occupations of the others represented a wide range of different jobs. The
      majority of the sample had a middle educational level. Most patients lived with
      their family or with a partner. According to self-assessments, 68% had average
      daily strain on their speaking voice. All patients were nonsmokers. The patients
      felt themselves more disturbed by somatic troubles as the general population.
      Heartburn was felt by nearly half of the patients. A little more than half of the
      patients suffered from globus sensation. Thus, it is not possible at present to
      explain the laryngeal contact granuloma by sociodemographic data, vocal stress,
      or special somatic complaints in this sample. Therefore a multifactorial etiology
      should be supposed.

PMID- 8574314
TI  - Intensive voice treatment in Parkinson disease: laryngostroboscopic findings.
AB  - As part of ongoing research to investigate and document the efficacy of intensive
      voice therapy to improve functional communication in patients with idiopathic
      Parkinson disease, 45 patients were enrolled in a controlled, randomized,
      prospective study. Pre- to posttreatment comparisons are presented here on 22 of
      those patients who underwent laryngeal imaging examination. Of the 22 patients,
      13 patients received intensive therapy aimed at increasing vocal and respiratory
      effort (VR), whereas nine received intensive therapy aimed at increasing
      respiratory effort (R) only. All patients had a pretreatment evaluation that
      included two (but sometimes only one) voice recordings and an otolaryngologic
      examination with laryngostroboscopy. At the completion of 4 weeks of therapy (16
      sessions), two voice recordings were made, and laryngostroboscopy was again
      performed. The pre- and posttherapy videolaryngostroboscopy tapes were then
      randomized and rated by four judges. Raters' findings were then compared with
      vocal intensity measured before and after therapy. The VR therapy group showed
      improvements on laryngostroboscopic variables: less glottal incompetence and no
      significant change in supraglottal hyperfunction after therapy. No differences
      were observed in the R-only group. The mean intensity increase in the VR therapy
      group was 12.5 dB, compared with a decrease of 1.9 dB in the R-only group. These
      findings suggest that in patients with Parkinson disease, intensive therapy
      focusing on phonatory effort improves adduction of the vocal folds as assessed by
      laryngostroboscopy. Differences in laryngeal function in these patients observed
      with fiberoptic laryngoscopy and rigid telescopic laryngoscopy are discussed.

PMID- 8574315
TI  - Combined-modality treatment of adductor spasmodic dysphonia with botulinum toxin
      and voice therapy.
AB  - A combined-modality treatment program consisting of botulinum toxin injection
      (Botox) and voice therapy was used to treat 17 subjects diagnosed with adductor
      spasmodic dysphonia (ADD SD). Ten subjects with ADD SD served as the control and
      were given Botox only. Voice therapy after Botox injection was directed toward
      reducing the hyperfunctional vocal behaviors, primarily glottal overpressure at
      voice onset and anterior-posterior squeezing. The results indicated that subjects
      who underwent combined-modality treatment maintained significantly higher mean
      airflow rates for significantly longer periods. Moreover, there was a carryover
      effect in these patients when they received Botox only. Adductor spasmodic
      dysphonia is treated most effectively when intrinsic laryngeal muscle spasms are
      reduced or eliminated by Botox injection and extrinsic hyperfunctional vocal
      behaviors are treated with voice therapy.

PMID- 8574316
TI  - A comparison of type I thyroplasty and arytenoid adduction.
AB  - Glottal incompetence is a common laryngeal disorder causing impaired swallowing
      and phonation. The resultant voice has been characterized as weak and breathy
      with a restricted pitch range. Currently, medialization thyroplasty and arytenoid
      adduction are two of the surgical treatments for patients with glottal
      incompetence. However, few studies have evaluated the changes in objective
      measures of speech with type I thyroplasty and arytenoid adduction. In this
      study, 59 patients with glottal incompetence underwent either type I thyroplasty
      or arytenoid adduction. Acoustic (jitter, shimmer, and harmonics-to-noise ratio)
      and aerodynamic (airflow, subglottic pressure, and glottal resistance) measures
      were obtained both pre- and postoperatively. No significant differences were
      found among acoustic or aerodynamic measures for operation type. However, a
      significant pre/postsurgery effect was observed for translaryngeal airflow. In
      addition, no significant differences were found among the measures for patients
      with traditional compared with nontraditional operative indications. Patients who
      developed glottal insufficiency due to previous laryngeal surgery (e.g., vocal
      fold stripping) demonstrated no statistically significant improvement in acoustic
      or aerodynamic measures following thyroplasty or arytenoid adduction.

PMID- 8574317
TI  - Environmental factors influencing the levels of indoor allergens.

PMID- 8574318
TI  - Allergen levels causing sensitisation, bronchial hyperreactivity and asthma.

PMID- 8574319
TI  - Role of the immune system in allergic children.

PMID- 8574320
TI  - Development of childhood eczema and its classification.

PMID- 8574321
TI  - Development of lower respiratory symptoms.

PMID- 8574322
TI  - Strategies for indoor allergen elimination.

PMID- 8574323
TI  - Allergen exposure and development of atopic diseases: progress and challenges.

PMID- 8574324
TI  - Immunochemical and molecular methods for defining and measuring indoor allergens:
      in dust and air.

PMID- 8574325
TI  - Direct observation of microcirculation of the basal region of rat gastric mucosa.
AB  - We modified and improved techniques for the intravital microscopic observation of
      the rat gastric microcirculation. The stomach of anesthetized rats was cut along
      the greater curvature, and the posterior wall of the glandular stomach was fixed
      in a chamber with the serosal side up and perfused with warmed Tyrode's solution.
      A portion of the muscularis externa was resected with the serosa to make an
      observation window. Vascular casts were studied histologically after the
      injection of Monastral blue B gelatin solution. Vascular casts revealed that most
      of the microvasculature observed in the window was not located in the submucosa,
      but in the basal part of the mucosa. Microscopic observation showed that the
      basal mucosal arterioles branched to form the mucosal capillaries, and the
      collecting venules from the mucosal surface were seen in cross-sections to drain
      into the venules located in the basal mucosa, without penetrating the muscularis
      mucosae. Topical application of acetylcholine (0.03-10 microM) to the window
      dilated the arterioles, and topical application of epinephrine (0.03-3 microM)
      constricted them dose-dependently without affecting the collecting venules and
      the venules. This method made possible the direct observation of the
      microvasculature in the basal mucosa of the stomach, in which common microvessel
      characteristics were shown.

PMID- 8574326
TI  - Oxidative stress in gastric mucosal injury: role of platelet-activating factor
      activated granulocytes.
AB  - Temporal and spatial changes due to oxidative stress in the rat gastric mucosa
      were visualized and quantified during the process of mucosal hemorrhagic change.
      The fluorescence associated with dichlorofluorescein (DCF), a hydroperoxide
      sensitive fluorochrome, increased 30 min after repeated electrical stimuli to the
      gastric artery. The increase in the fluorescence was enhanced in the area between
      two adjacent collecting venules. The content of platelet-activating factor (PAF),
      the activity of myeloperoxidase (MPO) in the gastric mucosa, the area of mucosal
      lesions, and the luminol-dependent chemiluminescence activity in zymosan-treated
      blood samples, obtained from the gastric vein, were measured and found to
      increase significantly 30 min after the stimuli. The intravenous injection of CV
      6209, a PAF antagonist, 5 min prior to the stimuli significantly inhibited the
      DCF activation, the increases in PAF level and MPO activity, the mucosal
      hemorrhagic change, and the elevation in chemiluminescence activity. In addition,
      continuous infusion of superoxide dismutase also inhibited all these changes,
      except for chemiluminescence activity. These results suggest that oxygen radicals
      derived from PAF-activated granulocytes induce oxidative stress, and that
      oxidative changes are actually implicated in the pathogenesis of gastric mucosal
      injury.

PMID- 8574327
TI  - Induction and intracellular localization of a 72-kDa heat shock protein in rat
      gastric mucosa after water-immersion stress.
AB  - We investigated the expression and changes in the intracellular localization of a
      72-kDa heat shock protein (HSP72) in rat gastric pyloric and fundic mucosa before
      and after water-immersion stress. Severe mucosal damage was found in the fundic
      mucosal area of the stomach after this stress. However, no mucosal lesion
      developed in the pyloric mucosal area. HSP72 in both the soluble and insoluble
      fractions of the pyloric and the fundic mucosal areas was significantly increased
      after water-immersion stress, peaking 6h after the initiation of the stress. The
      increase in HSP72 was more significant in the pyloric mucosal area than in the
      fundic mucosal area under both normal and stress conditions. The increase of
      HSP72 in the pyloric mucosal cells occurred prior to the formation of the mucosal
      lesions, whereas the increase of HSP72 in the fundic mucosal cells was observed
      after ulcer formation. An immunohistochemical study showed that HSP72 was
      constitutively expressed in the cytoplasm of the gastric mucosal cells, and that
      the intranuclear induction of HSP72 was remarkably intense in the pyloric mucosal
      cells, especially in the proliferative zone, compared with the fundic mucosal
      cells. Our results may suggest that HSP72 has an important cytoprotective
      function in gastric mucosal cells and that there is a "biophysical" difference
      between pyloric and the fundic mucosal cells.

PMID- 8574328
TI  - L-arginine and endogenous nitric oxide protect the gastric mucosa from endothelin
      1-induced gastric ulcers in rats.
AB  - We have reported that endothelin-1 induces gastric ulcer characterized by a
      potent long-lasting vasoconstriction of the regional microvasculature. Nitric
      oxide synthesized from L-arginine has been shown to regulated gastric mucosal
      blood flow, and inhibition of its synthesis has been shown to delay the healing
      of gastric ulcers. We examined the effect of exogenous L-arginine and the
      inhibition of nitric oxide synthesis on the development of endothelin-1-induced
      gastric ulcers. In rats anesthetized with urethane, a continuous intravenous
      infusion of L- or D-arginine (10 mg.kg-1.min-1) was followed, 15 min later, by a
      submucosal injection of endothelin-1 (200 pmol/kg) in the anterior wall of the
      gastric body. In another group, rats were intravenously pretreated with N omega
      nitro-L-arginine-methyl ester (1-10 mg/kg), a nitric oxide synthesis inhibitor,
      and then injected with endothelin-1 (40 pmol/kg). Twenty-four h later, L
      arginine, but not D-arginine, had significantly reduced the extent and the
      severity of the endothelin-1-induced ulcer (mucosal wall damage, 18.11 +/- 4.79%
      and 88.14 +/- 7.06%, respectively; mean +/- SD, P < 0.001), and the nitric oxide
      synthesis inhibitor (10 mg/kg) had increased the endothelin-1-induced mucosal
      damage (ulcer length, 3.8 +/- 1.2 mm and 1.1 +/- 0.2 mm, respectively, P < 0.01).
      Continuous gastric mucosal blood flow measurements showed that L-arginine
      antagonized the endothelin-1-induced vasoconstriction. L-arginine protected the
      gastric mucosa from the ulcerogenic action of endothelin-1 and antagonized its
      vasoconstrictive action. The inhibition of endogenous nitric oxide potentiated
      the ulcerogenic effect of endothelin-1 on rat gastric mucosa.

PMID- 8574329
TI  - Significantly lower prevalence of Helicobacter pylori in uremic patients than in
      patients with normal renal function.
AB  - The objective of the study was to evaluate the prevalence of Helicobacter pylori
      in patients with different degrees of renal function. Two hundred and twenty
      consecutive patients requiring gastroscopy for upper intestinal symptoms were
      enrolled in the study: group I (normal renal function, n = 127), group II
      (chronic renal failure, creatinine clearance > 5 < 90 ml/min, n = 59), and group
      III (hemodialysis therapy, n = 34). On endoscopy, biopsy specimens were taken for
      analysis of H. pylori infection by urease test and histology. The prevalence of
      H. pylori in patients with renal dysfunction proved to be significantly lower
      than that in patients with normal renal function (22.6% vs 37%, P < 0.05). The
      incidence of ulcer disease in patients with normal renal function was higher than
      that in uremic patients (14.2% vs 10.8%, not significant). These findings
      indicate that uremic patients seem to be partly protected against H. pylori
      infection.

PMID- 8574330
TI  - Alpha-fetoprotein-producing gastric carcinoma: biological properties of a
      cultured cell line.
AB  - We describe a gastric carcinoma cell line that has been maintained in vitro for
      more than 10 years and retains the capacity to produce a large amount of alpha
      fetoprotein. This cell line was isolated from a metastatic lymph node of a 63
      year-old male patient with advanced gastric carcinoma (T2N3P0H0M0) who showed
      high serum levels of alpha-fetoprotein. The primary tumor was moderately
      differentiated tubular adenocarcinoma and the lymph node was poorly
      differentiated adenocarcinoma without any particular pattern. The cultured cells
      grew as densely packed islet-like colonies with small polygonal cells. Electron
      microscopy revealed cells abundant in cytoplasmic organelles, with some cellular
      attachments being tight with junctional complexes and some being loose across
      intercellular spaces. The free cell surface had microvilli. The population
      doubling-time was 152 h at passage 58. Chromosomal analysis revealed the modal
      number to be 77, with numerous karyotype abnormalities. The tumorigenicity of the
      cultured cells in athymic nude mice was positive only when they were
      subcutaneously transplanted beneath a plastic plate, but when the cells were
      transplanted subcutaneously or administered by intrasplenic injection in intact
      or weakly irradiated nude mice, no tumorigenicity was shown. The cell line
      produced tumor-associated antigens, such as alpha-fetoprotein, carcinoembryonic
      antigen, and tissue polypeptide antigen. This cell line may be useful for
      comparative studies of different types of gastric carcinoma and alpha
      fetoproteins of different origins.

PMID- 8574331
TI  - Effects of intraduodenal administration of a low dose of cholecystokinin (CCK)
      antagonist (CR-1505) on plasma CCK concentration, intestinal CCK content, and
      levels of CCK mRNA.
AB  - The effects of the intraduodenal administration of a low dose of CR-1505 for 3-7
      days on the gene expression of cholecystokinin (CCK), plasma CCK concentration,
      and CCK content in the intestinal mucosa were examined in rats. The simultaneous
      changes of protein and enzyme content in the pancreas were also determined. CR
      1505 was infused continuously into the duodenum at a dose of 3 mg/kg per day,
      calculated to correspond to a dose of 150-200 mg/day in humans. Seven days after
      the administration of CR-1505, a liquid meal (4.5 kcal/3 ml) was introduced into
      the stomach and changes in the intestinal CCK content and plasma CCK
      concentration were examined. The level of CCK mRNA in the intestine was
      significantly higher in rats treated with CR-1505 than in control rats. The
      plasma CCK concentration, the CCK content of the intestinal mucosa, and the
      composition of pancreatic enzymes did not significantly differ in rats treated
      with CR-1505 and the untreated controls. In control rats, the administration of
      the liquid meal increased the plasma CCK concentration and significantly
      decreased the intestinal CCK content in water extracts, but did not affect the
      amount extracts in acid whereas the ingestion of the meal did not cause any
      significant changes in rats treated with CR-1505. These findings indicate that a
      low dose of CR-1505 stimulates the gene expression of CCK without enhancing CCK
      release or exerting an effect on the pancreas.

PMID- 8574332
TI  - A comparison of two prostaglandin analogues (enprostil vs misoprostol) in the
      treatment of acute duodenal ulcer disease.
AB  - We conducted a clinical trial to compare the efficacy and safety profile of two
      prostaglandin analogues, enprostil (35 micrograms twice daily) and misoprostol
      (200 micrograms four times daily) in the treatment of acute duodenal ulcers in
      214 patients. The two agents healed approximately 80% and in excess of 90% of
      duodenal ulcers after 4 and 6 weeks' therapy, respectively. There was a
      significantly lower ulcer healing rate in both treatment groups in smokers
      compared with non-smokers (P < 0.05). However, daytime and nighttime ulcer pain
      relief was achieved in fewer than 50% of patients by either agent. Diarrhea,
      which occurred in more than 40% of patients, was the predominant side effect, and
      occurred mainly during the first 2 weeks of therapy with either agent.
      Nevertheless, this side effect was mild and self-limiting in the majority of
      patients. Both agents were found to be safe and well tolerated by the majority of
      patients. We conclude that these prostaglandin analogues are safe and effective
      duodenal ulcer healing agents. Furthermore, there was very little difference
      between enprostil and misoprostol. The limiting factors, however, for their
      routine use as ulcer healing agents are their low efficacy with regard to ulcer
      pain relief and the high incidence of diarrhea.

PMID- 8574333
TI  - Bone metastasis from colorectal cancer in autopsy cases.
AB  - The incidence of bone metastasis from colorectal cancer is reported to be 10.7%
      in autopsy cases. However, the characteristics of the primary cancers, as well as
      the patterns of bone metastasis, remain unclear. We analyzed the clinical and
      autopsy records of 118 patients with primary colorectal cancer treated either
      surgically or conservatively and eventually autopsied between 1970 and 1987 at
      Toranomon Hospital in Tokyo. Bone metastasis was detected in 23.7% (28/118). The
      average age of patients with bone metastasis was lower than that in patients
      without bone metastasis (P < 0.02). Cancers to the rectum and cecum were
      accompanied by bone metastasis more frequently than cancers of other portions of
      the colon. Signet-ring cell carcinoma showed a high incidence of bone metastasis
      (P = 0.041). Bone metastasis from colorectal cancer was associated with liver or
      lung metastases (P < 0.0001). These results indicated that bone metastasis from
      colorectal cancer is not as infrequent as previously described.

PMID- 8574334
TI  - Changes in free radical-metabolizing enzymes and lipid peroxides in the liver of
      Long-Evans with cinnamon-like coat color rats.
AB  - We report changes in free radical-metabolizing enzymes and the increased
      generation of lipid peroxides associated with extreme metal accumulation in the
      liver of the Long-Evans with cinnamon-like coat color (LEC) rat, a new mutant
      strain displaying hereditary hepatitis and subsequent hepatocellular carcinoma.
      The activity of free radical-metabolizing enzymes and lipid peroxides, and the
      concentration of metal in the liver were determined sequentially after birth. Mn
      superoxide dismutase activity significantly increased immediately after the onset
      of hepatitis in LEC rats, whereas no remarkable change was observed in control
      rats. Cu, Zn-superoxide dismutase activity in LEC rats was similar to that in
      control rats. Glutathione reductase activity increased, while glutathione
      peroxidase activity was lower in LEC rats than in control rats throughout the
      observation periods. Lipid peroxides, estimated by thiobarbituric acid reaction,
      also increased 4- to 5-fold immediately after the onset of hepatitis in LEC rats.
      Copper concentration was 30- to 50-fold higher in the liver of LEC rats than in
      control rats, and the iron content also increased significantly before and after
      the onset of hepatitis. These findings suggested that an oxidant injury generated
      by toxic metals could be one of the factors responsible for hepatocellular damage
      in this unique hereditary hepatitis.

PMID- 8574335
TI  - Changes in immunoreactive insulin, C-peptide immunoreactivity, and immunoreactive
      glucagon in acute viral hepatitis.
AB  - Insulin and glucagon are thought to play important roles as hepatotrophic factors
      in acute viral hepatitis (AVH); however, few reports have investigated the
      responses and relationships of each of these hormones to liver damage in detail.
      We studied insulin and glucagon responses during the acute and recovery phases of
      AVH. We performed a glucose tolerance test (GTT) and an insulin sensitivity test
      (IST) in each phase in 11 patients with AVH. In 8 additional patients in the
      acute phase (total n = 19), were compared immunoreactive insulin (IRI) and C
      peptide immunoreactivity (CPR) levels with transaminase levels. In the acute
      phase, IRI concentrations were normal from fasting to 60 min, despite an
      increased CPR level. In the recovery phase, IRI and CPR levels increased
      significantly. Immunoreactive glucagon levels in both phases did not differ
      significantly from those in controls. During the IST, the insulin sensitivity
      index in both phases was significantly lower than that in the controls. Fasting
      IRI and sigma IRI showed significant negative correlations with transaminase
      levels. We found enhanced insulin secretion and a decrease in plasma insulin in
      the acute phase of AVH. The discrepancy between IRI and CPR responses in the
      acute phase suggests an increase in the degradation or consumption of insulin in
      the liver.

PMID- 8574336
TI  - Characteristics and prognosis of primary liver cancer in young patients in China.
AB  - To investigate the clinicopathologic characteristics of primary liver cancer
      (PLC) in young adults, 77 patients aged 35 or younger were compared with 603
      patients older than 35 years during the same period. In the young patients, PLC
      showed: (1) a low incidence detected at mass survey (young 15.6% vs older 28.7%,
      P < 0.05); (2) a low level of history of hepatitis (young 36.8% vs older 66.3%, P
      < 0.01); (3) a high incidence of positivity for hepatitis B surface antigen
      (HBsAg) (young 79.2% vs older 67.6%, P < 0.05); (4) a relatively low incidence of
      associated cirrhosis (young 64.9% vs older 90.7%, P < 0.01); (5) larger tumor
      size (PLC > 5 cm; young 87.0% vs older 73.0%, P < 0.01); and (6) a more advanced
      stage of the disease according to the TNM classification (stage III; young 29.9%
      vs older 18.2%, P < 0.05). It is suggested that hepatitis B virus (HBV) may play
      an important role in the development of PLC without associated liver cirrhosis in
      young patients. Close periodic surveillance of young adults who are positive for
      HBsAg is important to detect PLC at an early stage.

PMID- 8574337
TI  - Nitric oxide modulates pancreatic edema formation in rat caerulein-induced
      pancreatitis.
AB  - This study was designed to investigate the role of nitric oxide (NO) in the
      formation of pancreatic edema in caerulein-induced pancreatitis in rats.
      Pancreatitis was produced by two intraperitoneal injections of caerulein, and
      plasma amylase concentration, pancreatic edema index (pancreatic wet weight/body
      weight), and Evans blue extravasation (as a measure of vascular permeability)
      were evaluated 5 h after the first injection. Four doses (1, 2.5, 5, and 10
      mg/kg) of NG-nitro-L-arginine (L-NNA), an NO synthase inhibitor, were
      subcutaneously administered at -0.5, 0.5, 1.5, 2.5, and 3.5 h after the first
      injection of caerulein. L-NNA significantly lowered the edema index, the wet/dry
      weight ratio of the pancreas, and Evans blue extravasation in the rats with
      pancreatitis. The maximal effect was obtained by L-NNA at a dose of 2.5 mg/kg;
      this inhibited the increase in pancreatic edema formation from the control value
      by 60%-70%. Intraperitoneal injections (20 mg/kg, five times) of L-arginine, a
      substrate for NO production, partly reversed the L-NNA-induced inhibition of
      pancreatic edema formation, but D-arginine, an enantiomer of L-arginine, did not
      show any effect. Plasma amylase concentrations were not significantly affected by
      any dose of L-NNA, nor were they affected by L- or D-arginine. These findings
      strongly suggest that endogenous NO plays an important role in the formation of
      pancreatic edema in caerulein-induced pancreatitis in rats, probably by
      increasing vascular permeability and protein extravasation.

PMID- 8574338
TI  - Measurement of serum PSP/reg-protein concentration in various diseases with a
      newly developed enzyme-linked immunosorbent assay.
AB  - An enzyme-linked immunosorbent assay, based on two monoclonal antibodies (Hreg1-1
      and Hreg101-1) specific for pancreatic stone protein (PSP)/reg-protein, was
      developed to determine the concentration of this protein in serum from
      individuals with various diseases. The serum concentration of PSP/reg-protein was
      significantly higher in patients with various pancreatic diseases than in normal
      controls, and was also significantly higher in patients with acute pancreatitis
      or chronic relapsing pancreatitis than in patients with chronic pancreatitis.
      Furthermore, the serum PSP/reg-protein concentration was also significantly
      increased in liver cirrhosis, choledocholithiasis, and various cancers of the
      digestive system, and was extremely high in all patients tested with chronic
      renal failure. A significant correlation was apparent between the serum
      concentration of PSP/reg-protein and elastase-I in 68 patients with chronic
      pancreatitis or pancreatic cancer. Whereas only 7 of these patients showed a
      normal serum PSP/reg-protein concentration and a significantly increased elastase
      I concentration, 15 of these patients showed a significantly increased serum
      PSP/reg-protein concentration and a normal serum elastase-I concentration. These
      results indicate that the serum PSP/reg-protein concentration may reflect
      pancreatic damage, especially in acute pancreatitis, and may be a sensitive a
      marker for such damage as elastase-1, although false positivity was apparent in
      renal failure and in some patients with hepatic dysfunction or digestive system
      malignancies.

PMID- 8574339
TI  - Accumulation of 7 alpha-hydroxycholesterol in liver tissue of patients with
      cholesterol gallstones.
AB  - Patients with cholesterol gallstones have a reduced pool of bile acids. This
      study was undertaken to clarify the mechanism by which bile acid biosynthesis
      does not increase to supranormal levels to cause a reexpansion of the pool. We
      investigated the first two steps of the bile acid biosynthesis pathway by
      assaying the activities of cholesterol 7 alpha-hydroxylase, the rate-limiting
      enzyme in this pathway, and 3 beta-hydroxy-delta 5-C27-steroid
      dehydrogenase/isomerase, and by measuring the concentrations of 7 alpha
      hydroxycholesterol and 7 alpha-hydroxy-4-cholesten-3-one in liver specimens from
      ten patients with cholesterol gallstones and ten gallstone-free controls. In the
      patients with gallstones, cholesterol 7 alpha-hydroxylase activity, 3 beta
      hydroxy-delta 5-C27-steroid dehydrogenase/isomerase activity, and hepatic 7 alpha
      hydroxy-4-cholesten-3-one concentration did not significantly different from
      levels in controls, but hepatic 7 alpha-hydroxycholesterol concentration was more
      than twofold that of controls (12.9 +/- 2.6 vs 5.3 +/- 1.2 nmol/g liver, P <
      0.01). The concentration of 7 alpha-hydroxycholesterol positively correlated with
      the ratio of cholesterol 7 alpha-hydroxylase activity to 3 beta-hydroxy-delta 5
      C27-steroid dehydrogenase/isomerase activity (r = 0.93; P < 0.005) in the
      gallstone-free controls. In contrast, this correlation disappeared in the
      patients with gallstones. These results suggest a derangement of the normal 7
      alpha-hydroxycholesterol metabolism in the patients with gallstones. The reason
      for the accumulation of 7 alpha-hydroxycholesterol remains unclear; however, it
      is possible that, in patients with cholesterol gallstone, the accumulated 7 alpha
      hydroxycholesterol causes inappropriate suppression of cholesterol 7 alpha
      hydroxylase activity by product inhibition.

PMID- 8574340
TI  - Primary tubular adenocarcinoma arising in the duodenal limb of reconstructed
      gastroduodenostomy for signet-ring cell carcinoma of the stomach.
AB  - Adenocarcinoma of the small intestine is uncommon. Due to this paucity and the
      lack of specificity of symptoms, patients are usually seen late in the course of
      their illness, when curative therapy, mainly represented by extensive surgical
      resection, is unlikely. The authors report a case of primary well-differentiated
      tubular adenocarcinoma (T4N0M0) arising in the duodenal limb of a reconstructed
      Billroth I gastroduodenostomy, 9 years after a distal gastrectomy for signet-ring
      cell carcinoma of the stomach (T4N0M0). Evidence for excluding the possibility of
      a recurrence of the primary gastric cancer was based on the different histologic
      pattern, the long disease-free interval, and other features of the second
      neoplasm. Relatively early diagnosis of the neoplasm, followed by curative
      surgical therapy was made possible by the early onset of the obstructive symptoms
      and the favorable anatomical location of the tumor.

PMID- 8574341
TI  - Castleman's disease of the abdomen and pelvis: report of three cases and a review
      of the literature.
AB  - Three cases of Castleman's disease (CD) of the abdomen and pelvis are reported.
      Tumoral lesions were located in the lymph nodes of the head of the pancreas, the
      gastropancreatic fold, and around the left iliac artery. Histologically, all the
      tumoral lesions demonstrated the hyalinevascular type of CD. This unusual
      presentation made CD difficult to diagnose preoperatively, since these lesions
      more closely resembled malignant tumors on computed tomography and angiography.
      We discuss the problems of diagnosing and classifying CD, together with a review
      of the literature.

PMID- 8574342
TI  - Three cases of primary biliary cirrhosis associated with bronchial asthma.
AB  - The association of primary biliary cirrhosis (PBC) and bronchial asthma was
      observed in three patients. All of these patients were female (53, 54, and 41
      years old, respectively), and were positive for antimitochondrial antibodies. The
      patients fulfilled the diagnostic criteria of both PBC and bronchial asthma.
      Bronchial asthma preceded PBC in two patients, and the reverse order was seen in
      the other. Patient the clinical symptoms were mainly due to the bronchial asthma.
      Two patients had asymptomatic PBC and the third patient complained of pruritus.
      The liver histology showed mild to moderate eosinophilic infiltration in addition
      to the ductal and hepatic parenchymal changes characteristic of PBC. A survey of
      266 cases of PBC referred to us disclosed that, in 6 of these, the PBC was
      associated with bronchial asthma, while no association with bronchial asthma was
      the material of found in 166 patients with viral hepatitis in our liver biopsy
      files. The 3 present cases we experienced suggest that bronchial asthma may be
      included in the list of extrahepatic diseases associated with PBC. The
      significance of this association is unclear and may merit further study. Steroid
      therapy, which is known to cause adverse effects in PBC, was employed for
      bronchial asthma in these 3 patients. Another therapeutic approach will have to
      be considered in patients with bronchial asthma associated with PBC.

PMID- 8574343
TI  - Late onset hepatic failure due to hepatitis B virus with mutations in the pre
      core region.
AB  - A 60-year-old man complained of severe general fatigue on October 11, 1992.
      Pertinent laboratory findings were: aspantate aminotransferase (AST) 1920 IU,
      alanine aminotransferase (ALT) 2050 IU, and total bilirubin (T. Bil) 124
      micromol/l (normal range, 0-17 micromol/l). Virological assay revealed that
      hepatitis B surface antigen (HBsAg), anti-hepatitis B e (HBe), anti-HBc, and
      immunoglobulin M (IgM) anti-HBc were positive, and anti-HBs, HBeAg, and anti
      delta antibody were negative. A diagnosis of acute hepatitis due to hepatitis B
      virus was made. Despite a decrease in transaminase, jaundice worsened and
      prothrombin time was prolonged. On the 60th day of hospitalization, massive
      ascites developed, but the patient's consciousness was not impaired. Although,
      albumin and diuretics were given, the ascites further increased. Paracentesis of
      2000 ml of ascitic fluid was performed twice a week. On the 120th day of
      hospitalization, the patient passed black stools and he exhibited renal failure 3
      weeks later. Although severe jaundice persisted, he was still alert. On the 150th
      day of hospitalization, massive gastrointestinal bleeding occurred, due to
      hemorrhagic gastritis. Despite receiving intensive care, the patient died.
      Determination of the HBV DNA sequence revealed two point mutations in the pre
      core region; these have not been reported elsewhere.

PMID- 8574344
TI  - Intrahepatic sarcomatous cholangiocarcinoma.
AB  - A 77-year-old man, diagnosed with a liver tumor, was referred to our hospital.
      Abdominal ultrasonography demonstrated a low echoic mass in the liver S2 region,
      and abdominal CT confirmed the presence of a round low-density mass 7 cm in
      diameter. Enhanced angio-computed tomography (CT) showed a ring-like form with a
      pale periphery. In the delayed phase of angio-CT, the inside of the mass was
      enhanced, showing septal stricture. Abdominal magnetic resonance imaging (MRI)
      revealed a heterogenous low intensity area in T1-weighted images, with a clear
      high intensity border becoming apparent in T2-weighted images. Stretching of the
      hepatic artery was evident on the arterial phase of angiography, while an
      avascular area was apparent in the lateral segment of the liver in the portal
      phase. Lateral segmentectomy was performed. The size of the tumor was 6 x 6 x 5
      cm. On macroscopic cross section, it was white and clearly demarcated from the
      surrounding tissue. Microscopic observation of H&E-stained specimens did not show
      any glandular formation. The tumor consisted of an irregular fascicular
      arrangement of spindle-shaped and round cells with poor intercellular adhesion.
      While there was no region containing differentiated epithelial components, silver
      impregnation staining revealed structures resembling regenerating bile ducts. The
      tumor cells were positive for wide-keratin, and for vimentin staining. Tumor
      cells were carcinoembryonic antigen (CEA)-positive and alpha-feto protein (AFP)
      negative. From the above findings, the tumor was judged to have originated from
      epithelium rather than from mesenchymal elements. The final diagnosis was
      intrahepatic cholangiocarcinoma with secondary sarcomatous transformation, rather
      than hepatocellular carcinoma.

PMID- 8574345
TI  - Changes in gene expression of cholecystokinin-A receptor after induction of
      pancreatitis by pancreatic duct occlusion in rats.
AB  - Serial changes in the levels of cholecystokinin (CCK)-A receptor mRNA in the
      pancreas after pancreatic duct occlusion were examined in rats. CCK-A receptor
      mRNA level was determined by Northern blot analysis with a rat CCK-A-receptor
      cDNA probe. The level of CCK-A receptor mRNA first decreased, reaching the lowest
      level 7 days after occlusion, and then began to increase. On day 14, it had
      completely recovered to the control level and it remained at that level until 28
      days after occlusion.

PMID- 8574346
TI  - The origin of the oxidative burst in plants.
AB  - A large number of publications recently have drawn strong analogies between the
      production of active oxygen species in plant cells and the "oxidative burst" of
      the phagocyte, even to the point of constructing elaborate models involving
      receptor mediated G-protein activation of a plasmalemma NADPH oxidase in plant
      cells. However there are potentially other active oxygen species generating
      systems at the plant cell surface. The present work examines these alternatives
      with particular emphasis on the rapid production of active oxygen species, in
      common with a number of other systems, by suspension-cultured cells of French
      bean on exposure to an elicitor preparation from the fungal pathogen
      Colletotrichum lindemuthianum. The cells show a rapid increase in oxygen uptake
      which is followed shortly afterwards by the appearance of a burst of these active
      oxygen species, as measured by a luminescence assay, which is probably all
      accounted for by hydrogen peroxide. An essential factor in this production of
      H2O2 appears to be transient alkalinization of the apoplast where the pH rises to
      7.0-7.2. Dissipation of this pH change with a number of treatments, including
      ionophores and strong buffers, substantially inhibits the oxidative burst. Little
      evidence was found for enhanced activation of a membrane-bound NADPH oxidase.
      However the production of H2O2 under alkaline conditions can be modelled in vitro
      with a number of peroxidases, one of which, an M(r) 46,000 wall-bound cationic
      peroxidase, is able to sustain H2O2 production at neutral pH unlike the other
      peroxidases which only show low levels of this reaction under such conditions and
      have pH optima at values greater than 8.0. On the basis of such comparative pH
      profiles between the cells and the purified peroxidase and further inhibition
      studies a direct production of H2O2 from the wall peroxidase in French bean cells
      is proposed. These experiments may mimic some of the responses to plant
      pathogens, particularly the hypersensitive response, which is an important
      feature of resistance. A cell wall peroxidase-origin for the oxidative burst is
      clearly different from a model consisting of receptor activation of a plasmalemma
      localised NADPH oxidase generating superoxide. An alternative simple and rapid
      mechanism thus exists for the generation of H2O2 which does not require such
      multiple proteinaceous components.

PMID- 8574347
TI  - Batch-to-batch variation of Chelex-100 confounds metal-catalysed oxidation.
      Leaching of inhibitory compounds from a batch of Chelex-100 and their removal by
      a pre-washing procedure.
AB  - Removal of adventitious redox-active metals from buffers by treatment with Chelex
      resin is a widely used procedure in free radical research. Use of a new batch of
      Chelex-100 resin in our laboratory coincided with a sudden inability to oxidise
      low-density lipoprotein with copper. We found that copper-mediated oxidation of
      ascorbate in water treated with the same batch of Chelex was inhibited when
      compared with untreated water and water treated with a different batch of the
      resin. Washing the Chelex removed the inhibitory effect suggesting that material
      was leaching from the resin. The washing procedure for Chelex-100 described is
      simple and can be scaled up. Oxidation of ascorbate with low concentrations of
      copper can be used to test the quality of batches of the resin.

PMID- 8574348
TI  - Nitration of tyrosine by hydrogen peroxide and nitrite.
AB  - Peroxynitrite anion is a powerful oxidant which can initiate nitration and
      hydroxylation of aromatic rings. Peroxynitrite can be formed in several ways,
      e.g. from the reaction of nitric oxide with superoxide or from hydrogen peroxide
      and nitrite at acidic pH. We investigated pH dependent nitration and
      hydroxylation resulting from the reaction of hydrogen peroxide and nitrite to
      determine if this reaction proceeds at pH values which are known to occur in
      vivo. Nitration and hydroxylation products of tyrosine and salicyclic acid were
      separated with an HPLC column and measured using ultraviolet and electrochemical
      detectors. These studies revealed that this reaction favored hydroxylation
      between pH 2 and pH 4, while nitration was predominant between pH 5 and pH 6.
      Peroxynitrite is presumed to be an intermediate in this reaction as the
      hydroxylation and nitration profiles of authentic peroxynitrite showed similar pH
      dependence. These findings indicate that hydrogen peroxide and nitrite interact
      at hydrogen ion concentrations present under some physiologic conditions. This
      interaction can initiate nitration and hydroxylation of aromatic molecules such
      as tyrosine residues and may thereby contribute to the biochemical and toxic
      effects of the molecules.

PMID- 8574349
TI  - Depletion of alpha-tocopherol in human atherosclerotic lesions.
AB  - Estimations of alpha-tocopherol content were made on a series of human necropsy
      samples of normal arterial wall and of atherosclerotic lesions. The results were
      compared with stage of lesion, shown by histology, and with the amounts of
      cholesterol and hydroxycholesterols in the same lesions. The ratio of alpha
      tocopherol to cholesterol levels varied widely in normal arterial wall but was
      consistently low in lesions, especially in lesions rich in macrophage foam cells.
      The results suggested that significant accumulation of hydroxycholesterols, found
      almost exclusively in lesions, only occurred when alpha-tocopherol levels were
      low in relation to the cholesterol content. This suggests that oxidative activity
      in the lesion may lead to significant oxidation of constituents of low-density
      lipoprotein only after alpha-tocopherol has been depleted.

PMID- 8574351
TI  - Linear and non linear competition plots in the deoxyribose assay for
      determination of rate constants for reaction of nonsteroidal antiinflammatory
      drugs with hydroxyl radicals.
AB  - Performing the deoxyribose (DR) assay for determination of the rate constants for
      reaction of non steroidal antiinflammatory drugs with hydroxyl radicals led to
      some unusual competition plots. The molecules from the arylpropionic family of
      drugs: ibuprofen, flurbiprofen, ketoprofen and naproxen produced the linear
      relationship. However, acemetacin, diclofenac Na, flufenamic acid, indometacin,
      indometacin, niflumic acid, tolmetin Na and sulindac presented non linear
      competition plots manifesting at relatively low drug concentrations. This effect
      was corrected by increasing DR concentrations from 2.8 mM to 15 mM. The
      modification did not affect rate constants values for those derivatives which
      already presented a linear plot at 2.8 mM, but allowed to calculate rate
      constants for other compounds. It is suggested that the experimental conditions
      have to be adapted particularly for those derivatives with a relatively high rate
      constant for reaction with the radical species. The oxicam derivatives (tenoxicam
      and piroxicam) presented another kind of deviation that revealed a prooxidant
      effect in this system: non linear plots were also observed at relatively low drug
      concentrations, but in the opposite direction than for the other molecules. This
      last effect was independent of DR concentration but could be corrected by
      increasing ascorbate concentration in the system.

PMID- 8574350
TI  - EPR studies on the effects of complexation of heme by hemopexin upon its
      reactions with organic peroxides.
AB  - Hemopexin, a heme-binding serum glycoprotein, is thought to play an important
      role in the prevention of oxidative damage that may be catalysed by free heme.
      Through the use of EPR techniques, the generation of free radicals from organic
      hydroperoxides by heme and heme-hemopexin complexes, and the concomitant
      formation of high oxidation-state iron species has been studied; these species
      are implicated as causative agents in processes such as cardiovascular disease
      and carcinogenesis. From the rates of production of these species from both n
      alkyl and branched hydroperoxides, it has been inferred that the dramatic
      reduction in the yield of oxidising species generated by heme upon its
      complexation with hemopexin arises from steric hindrance of the access of
      hydroperoxide to the bound heme.

PMID- 8574352
TI  - The susceptibility of low density lipoprotein to chemical oxidation is closely
      related to proneness to biological modification.
AB  - U937 is a monocytic cell line dependent on low density lipoprotein (LDL) receptor
      mediated uptake of cholesterol for proliferation. However, exposure of U937 cells
      to LDL also results in an oxidative modification of LDL. We report here that the
      oxidative modification of LDL by U937 cells results in inhibition of growth and
      cell death. This finding suggests that analysis of U937 cell growth in presence
      of LDL may be used to determine the susceptibility of LDL to biological oxidative
      modification. There was an inverse association between the effect of LDL on U937
      cell growth and the rate of degradation of U937 cell-modified LDL in mouse
      peritoneal macrophages (r = -0.82, p < 0.05) suggesting a coupling between
      proneness of LDL to develop cytotoxicity and affinity for scavenger receptors. In
      a group of young post-infarction patients (n = 18) the susceptibility of LDL to
      chemical oxidation as determined by analysis of the lag phase for formation of
      conjugated diens in presence of copper ions was compared with the biological
      modification of LDL as assessed by analysis of U937 cell growth in presence of
      LDL. The results demonstrated a close relation between the estimates of chemical
      oxidation and biological modification (r = 0.86, p < 0.005) suggesting that LDL,
      which is prone to become oxidised by copper also is more prone to become modified
      by cells in vivo.

PMID- 8574353
TI  - Free radical generation at the solid/liquid interface in iron containing
      minerals.
AB  - The potential for free radical release has been measured by means of the spin
      trapping technique on three kinds of iron containing particulate: two asbestos
      fibers (chrysotile and crocidolite); an iron-exchanged zeolite and two iron
      oxides (magnetite and haematite). DMPO (5,5'-dimethyl-1-pirroline-N-oxide), used
      as spin trap in aqueous suspensions of the solids, reveals the presence of the
      hydroxyl and carboxylate radicals giving rise respectively to the two adducts
      [DMPO-OH] and [DMPO-CO2], each characterized by a well-defined EPR spectrum. Two
      target molecules have been considered: the formate ion to evidence potential for
      hydrogen abstraction in any biological compartment and hydrogen peroxide, always
      present in the phagosome during phagocytosis. The kinetics of decomposition of
      hydrogen peroxide has also been measured on all solids. Ferrozine and
      desferrioxamine, specific chelators of Fe(II) and Fe(III) respectively, have been
      used to remove selectively iron ions. Iron is implicated in free radical release
      but the amount of iron at the surface is unrelated to the amount of radicals
      formed. Only few surface ions in a particular redox and coordination state are
      active. Three different kinds of sites have been evidenced: one acting as H
      abstracter, the other as a heterogeneous catalyst for hydroxyl radical release,
      the third one related to catalysis of hydrogen peroxide disproportionation. In
      both mechanisms of free radical release, the Fe-exchanged zeolite mimics the
      behaviour of asbestos whereas the two oxides are mostly inert. Conversely
      magnetite turns out to be an excellent catalyst for hydrogen peroxide
      disproportionation while haematite is inactive also in this reaction. The results
      agree with the implication of a radicalic mechanism in the in vitro DNA damage
      and in the in vivo toxicity of asbestos.

PMID- 8574354
TI  - The protective effects of eugenol on carbon tetrachloride induced hepatotoxicity
      in rats.
AB  - Our earlier studies in vitro have shown that eugenol inhibits liver microsomal
      monooxygenase activities and carbon tetrachloride (CCl4)-induced lipid
      peroxidation (Free Rad. Res. 20, 253-266, 1994). The objective of the present
      investigation was to study the in vivo protective effect of eugenol against CCl4
      toxicity. Eugenol (5 or 25 mg/kg body wt) given orally for 3 consecutive days did
      not alter the levels of serum glutamic oxalacetic transaminase (SGOT), microsomal
      enzymes such as cytochrome P450 reductase, glucose-6-phosphatase (G-6-Pase)
      xenobiotic-metabolizing enzymes (aminopyrine-N-demethylase, N
      nitrosodimethylamine-demethylase and ethoxyresorufin-O-deethylase) and liver
      histology. Doses of eugenol (5 or 25 mg/kg) administered intragastrically to each
      rat on three consecutive days i.e. 48 hr, 24 hr and 30 min before a single oral
      dose of CCl4 (2.5 ml/kg body wt) prevented the rise in SGOT level without
      appreciable improvement in morphological changes in liver. Eugenol pretreatment
      also did not influence the decrease in microsomal cytochrome P450 content, G-6
      Pase and xenobiotic-metabolizing enzymes brought about by CCl4. Since eugenol is
      metabolized and cleared rapidly from the body, the dose schedule was modified in
      another experiment. Eugenol (0.2, 1.0, 5.0 or 25 mg/kg) when given thrice orally
      i.e. prior to (-1 hr) along with (0 hr) and after (+3 hr) the i.p. administration
      of CCl4 (0.4 ml/kg) prevented significantly the rise in SGOT activity as well as
      liver necrosis. The protective effect was more evident at 1 mg and 5 mg eugenol
      doses. However, the decrease in microsomal G-6-Pase activity by CCl4 treatment
      was not prevented by eugenol suggesting that the damage to endoplasmic reticulum
      is not protected. The protective effect of eugenol against CCl4 induced
      hepatotoxicity is more evident when it is given concurrently or soon after rather
      than much before CCl4 treatment.

PMID- 8574355
TI  - The Optic Neuritis Treatment Trial. Putting the results in perspective. The Optic
      Neuritis Study Group.

PMID- 8574356
TI  - Relative pupillary sparing third nerve palsies. To arteriogram or not?
AB  - Ten consecutive patients with acute relative pupillary sparing third nerve
      palsies were enrolled in a prospective study to determine the prevalence of
      intracranial aneurysm. All patients were imaged with either cerebral angiography
      or magnetic resonance angiography. None of the patients demonstrated an
      intracranial aneurysm. The prevalence of aneurysm in patients with relative
      pupillary sparing third nerve palsies may be low enough to preclude the use of
      routine angiography in this condition.

PMID- 8574357
TI  - The treatment of superior oblique myokymia utilizing the Harada-Ito procedure.
AB  - A woman with superior oblique myokymia (SOM) was cured of her condition by
      performing a Harada-Ito procedure. This procedure involves transposing the
      anterior portion of the superior oblique tendon, which is responsible for
      cyclorotation, nasally to create an effective weakening of the anterior portion
      of the tendon instead of temporal displacement utilized for superior oblique
      paresis. We measured the patient's eye movements before and after surgery, using
      the magnetic search coil technique, and confirmed that (1) the SOM was abolished
      and (2) vertical eye movements, including saccades, were unaffected.

PMID- 8574358
TI  - Intermittent esotropia associated with rippling muscle disease.
AB  - PURPOSE: We report a rare myopathy known as rippling muscle disease, with the
      unique feature of extraocular muscle involvement, presenting as a variable
      esotropia. METHODS: Chart review with a review of the literature. RESULTS:
      Neurologic and neuro-ophthalmic examinations as well as electromyography and
      muscle biopsy confirm that this case closely resembles those described in the
      literature with the additional feature of a variable esotropia. CONCLUSION:
      Rippling muscle disease may be associated with intermittent esotropia. The
      pathophysiology of this disorder is unknown, but the intermittent esotropia is
      likely related to "rippling" of the medial recti.

PMID- 8574360
TI  - Magnetic resonance imaging of the brain in nonarteritic ischemic optic
      neuropathy.
AB  - We wished to determine whether the number of central nervous system (CNS) white
      matter lesions on magnetic resonance imaging (MRI) is increased in patients with
      nonarteritic ischemic optic neuropathy (NAION). T2-Weighted axial images of the
      brain in 13 patients with acute NAION and 16 age-matched controls were used to
      tabulate the number of subcortical and periventricular white matter lesions.
      Groups were compared by t test for means, the Wilcoxon-Mann-Whitney rank-sum
      test, and chi-square test for proportions with at least one lesion. The mean
      number of CNS white matter ischemic lesions in the NAION group was 4.0 (range 0
      20) as compared to 1.4 (range 0-7) in the control group. The difference in these
      samples suggested a significant increase in NAION (p = 0.069, rank-sum test). The
      proportions of patients with at least one lesion were not significantly different
      (53.8% NAION vs. 56.3% controls). The data suggest an increased number of CNS
      white matter lesions in patients with NAION.

PMID- 8574359
TI  - Angiocentric T-cell lymphoma presenting with multiple cranial nerve palsies and
      retrobulbar optic neuropathy.
AB  - Angiocentric T-cell lymphoma (lymphomatoid granulomatosis) may present with
      prominent central nervous system (CNS) findings with variable radiographic
      features. We describe a patient who presented with multiple cranial nerve palsies
      involving the left optic nerve, left facial nerve, left ocular motor nerves, and
      bilateral acoustic nerves. Enhancement of the right temporal meninges and a
      cavernous sinus mass were noted on magnetic resonance (MR) scan. A right temporal
      craniectomy and meningeal biopsy were performed. Meningeal biopsy revealed
      atypical angiocentric granulomatous lymphoid infiltrates without associated
      necrosis, giant cells, or granuloma formation. Morphologic and T-cell, receptor
      gene rearrangement findings were diagnostic of an angiocentric T-cell lymphoma.
      Retrobulbar optic neuropathy and multiple cranial nerve palsies may be the
      presenting features of angiocentric T-cell lymphoma. The neurologic and unique
      radiographic changes in our case expand the previously reported findings in CNS
      angiocentric T-cell lymphoma.

PMID- 8574361
TI  - Optic nerve compression from a basal encephalocele.
AB  - A woman developed headaches, transient visual obscurations, anosmia, and
      decreased visual acuity. Ocular examination showed bilateral pulsatile proptosis
      and disc edema with choroidal folds. Standardized ophthalmic echography showed
      absence of bony orbital roofs, prominent dural pulsations, direct apposition of
      brain parenchyma and orbital tissues, and echographic signs suggesting bilateral
      optic nerve compression. CT and MRI showed a large defect in the floor of the
      anterior cranial fossa. The cribriform plate, both orbital roofs, and sphenoid
      bones were displaced by a large basal encephalocele. Clinical improvement
      followed reconstruction of the anterior cranial fossa and decompression of both
      optic nerves.

PMID- 8574362
TI  - Acetylcholine receptor antibodies in patients with Graves' ophthalmopathy.
AB  - OBJECTIVES: To determine the frequency and clinical correlates of acetylcholine
      receptor (AChR) antibody seropositivity in patients with Graves' ophthalmopathy.
      MATERIALS AND METHODS: Fifty consecutive new patients with Graves' ophthalmopathy
      diagnosed in an outpatient neuro-ophthalmology practice underwent determination
      of AChR-binding antibodies. Clinical and biochemical thyroid variables were
      compared between seropositive and seronegative patients. Clinical variables
      included age, sex, thyroid disorder, and duration and course of illness.
      Biochemical variables included thyroid hormone levels and thyroid antibodies.
      Seropositive patients were followed clinically to identify signs of myasthenia
      gravis. RESULTS: Four of 50 (8%) patients had definitely elevated levels of AChR
      binding antibodies. No obvious differences existed between the seropositive and
      seronegative groups in regards to age, sex, underlying thyroid disorder,
      biochemical thyroid state, presence of thyroid antibodies, or duration and course
      of their disease. None of the four seropositive patients developed signs of
      myasthenia gravis during the median follow-up period of 4.5 years. CONCLUSION:
      AChR-binding antibody seropositivity occurs in a small proportion of patients
      with Graves' ophthalmopathy but, by itself, does not necessarily identify an
      individual with concurrent myasthenia gravis or an individual at risk to develop
      myasthenia gravis.

PMID- 8574364
TI  - Bilateral disc edema in an adolescent girl.

PMID- 8574363
TI  - Optic neuropathy, headache, and diplopia with MRI suggestive of cerebral
      arteritis in relapsing polychondritis.
AB  - The pathogenesis of central nervous system disease in relapsing polychondritis
      (RPC) is unknown but may be related to cerebral arteritis. Previous reports have
      described clinical and histopathologic evidence of cerebral vasculitis in RPC;
      however, a neuroimaging correlate has not been reported. We present a 36-year-old
      man with neuro-ophthalmic features of RPC whose magnetic resonance imaging
      revealed multifocal gray- and white-matter high intensities. This pattern is
      consistent with cerebral arteritis as described in other systemic vasculitides.

PMID- 8574365
TI  - Intracranial hypertension and the syndrome of acquired hyperopia with choroidal
      folds.
AB  - An idiopathic syndrome of acquired hyperopia with choroidal folds has been
      characterized. Orbital imaging correlates of this syndrome include flattening of
      the posterior globe and distention of the perioptic subarachnoid space. The
      mechanism responsible for the clinical and radiographic findings of this syndrome
      is undefined. Two patients with unusual presentations of papilledema are reported
      whose clinical and radiographic findings were otherwise identical to those
      described in the idiopathic syndrome of acquired hyperopia with choroidal folds.
      One patient had unilateral disc edema and bilateral choroidal folds. The other
      patient had bilateral choroidal folds observed 2 years before he developed
      papilledema in both eyes. Both patients had intracranial hypertension, idiopathic
      in the first, and related to severe chronic obstructive pulmonary disease and cor
      pulmonale in the second. A third patient is also described who had typical
      clinical and orbital imaging findings of idiopathic unilateral acquired hyperopia
      with choroidal folds. He was also found to have mild intracranial hypertension.
      Intracranial hypertension can cause acquired hyperopia and choroidal folds and
      may be the underlying mechanism in some patients with what appears to be
      idiopathic acquired hyperopia with choroidal folds.

PMID- 8574366
TI  - Vasculature and morphometry of the optic canal and intracanalicular optic nerve.
AB  - OBJECTIVES: To study the bony structure of the optic canal and the vasculature of
      the intracanalicular optic nerve in human cadavers. MATERIALS AND METHODS: Gross
      and microscopic examinations were performed in 25 optic canals from 13 cadavers
      to study the pattern of vascular supply of the intracanalicular optic nerve.
      Neoprene latex was injected through the most proximal part of the ophthalmic
      artery in seven optic canals. The intracanalicular branches from the ophthalmic
      artery were carefully identified and quantified. Quantitative measurements of the
      canal length, canal thickness, canal transverse area, optic nerve transverse
      area, and subdural space were done for the other 18 canals by means of
      semiautomated morphometric analysis system. Each canal was divided into anterior,
      middle, and posterior parts for better visualization and measurement. RESULTS:
      The ophthalmic artery gives off three branches that supply the intracanalicular
      optic nerve: medial collateral branch, lateral collateral branch, and ventral
      branch. Each branch pierces the dura and then supplies the nerve through the pia
      mater. The middle medial wall was the thinnest bony part of the canal (0.31 +/-
      0.06 mm). The optic canal, optic nerve, and subdural space transverse area varied
      at different transection levels. The narrowest space was in the middle part of
      the optic canal. The mean subdural cross-sectional space was only 1.84 mm2. This,
      multiplied by the average canal length (11.79 mm), can be considered the
      potential space for hemorrhage, optic nerve edema, or hematoma. CONCLUSIONS: The
      vasculature within the bony canal is extremely delicate. Due to the limitation of
      this space, even a tiny amount of blood or swelling of the nerve (21.69 mm3) may
      cause optic nerve compression. It appears that these vessels could easily be
      disrupted in closed head injury by a shearing or concussive force, leading to
      ischemic infarction of the optic nerve. Since the narrowest portion of the canal
      is in the middle portion, it is the middle part of the optic canal that is most
      critical in doing an optic canal decompression.

PMID- 8574367
TI  - Ocular motor systems. Part 2: Nuclear and supranuclear systems.

PMID- 8574368
TI  - Common foot problems. 1967.

PMID- 8574369
TI  - Sonographic evaluation of interdigital neuromas.
AB  - Fifty surgical patients with symptoms suggestive of Morton's neuroma underwent
      preoperative ultrasound examination of the forefoot using a 7.5 MHz transducer.
      Fifty-five neuromas were excised. Of these, one neuroma had a ganglion associated
      with it and five neuromas were recurrent. Four feet had adjacent neuromas.
      Ultrasound accurately predicted the presence, location and size of the neuromas
      in 98% of the cases. There were no false positives. In all cases in which a
      neuroma was predicted by ultrasound, it was confirmed grossly at the time of
      surgery and later by histological exams. We conclude that ultrasound is an
      accurate technique in the diagnosis of interdigital neuromas.

PMID- 8574370
TI  - Clawtoe deformity following vascularized fibula graft.
AB  - The free vascularized fibula graft has been an increasingly useful tool in
      orthopaedic surgery. In addition to its many applications, the reported low donor
      site morbidity has helped make this a popular treatment modality. Isolated flexor
      hallucis longus flexion contracture has been reported in the literature; however,
      multiple ipsilateral clawtoe deformity has not been reported. We describe two
      cases of multiple clawtoe deformity following ipsilateral harvest of a free
      vascularized fibula graft.

PMID- 8574371
TI  - Efficacy of first-time steroid injection for painful heel syndrome.
AB  - The purpose of this study was to evaluate the results of a single injection of
      corticosteroids in patients with painful heel syndrome. Twenty-seven heels in 24
      patients were injected with a combination of 1 ml of lidocaine and 1 ml of
      betamethasone (6 mg). These patients had never previously received an injection
      to their heels and had continued symptoms of pain after a trial of other
      nonoperative treatment modalities. After the injection, patients were seen and
      surveyed periodically for a period of 5 months to 8 months. The amount of pain
      relief that they obtained, the length of time this lasted, and the amount of heel
      pain present at the final follow-up were recorded. Based on the results of our
      study, we believe that a steroid injection is a reasonable adjunct in the
      treatment of painful heel syndrome, but that it is unlikely to provide permanent
      pain relief.

PMID- 8574372
TI  - Gout as a source of sesamoid pain.
AB  - Isolated gout of a great toe sesamoid has not been described previously. We
      present a case of gout of the medial sesamoid in a young athlete. Because a
      diagnosis is often elusive in patients with sesamoid pain, it is possible that
      other cases of gout of a hallucal sesamoid have gone unrecognized. Consideration
      of this diagnosis might lead to curative medical therapy precluding the need for
      surgical intervention.

PMID- 8574373
TI  - Giant cell tumor of bone in the foot and ankle.
AB  - Giant cell tumor of bone has been shown to behave more aggressively when located
      in the wrist and hand. Although nearly 4% of giant cell tumors arise in the foot
      and ankle, biological features specific to this location have not been
      identified. In our experience with more than 300 cases of giant cell tumor, 12
      arose in the foot and ankle and were followed for more than 2 years. These
      included nine females and three males ranging in age from 15 to 52 years (mean
      age, 29.5 years). All patients presented with pain of 5.0 months' mean duration
      and 9 of 12 tumors demonstrated aggressive radiographic features, including bone
      erosion and destruction; five had either invasion of a joint or a soft tissue
      mass present. Unlike the hand, where metacarpal and phalangeal lesions are
      common, no tumors arose in the forefoot and nine of the tumors were present in
      the ankle region. Four patients were treated with resection (no recurrence), two
      with curettage and cement packing (one recurrence), and six with curettage and
      autologous bone graft (two recurrences), which resulted in an overall recurrence
      rate of 25%. None of the recurrent tumors have returned after additional
      treatment, which consisted of curettage and cement packing in two cases and
      resection in one case. Five tumors (four primary, one recurrent) were treated
      with local resection and reconstruction with no major complications and with no
      amputations performed. Thus, giant cell tumors of the foot and ankle can be
      treated with local procedures, which result in recurrence rates similar to those
      found in more common locations.

PMID- 8574374
TI  - Influence of malalignment of feet on the plantar pressure pattern in running.
AB  - When overuse injuries of the lower limbs are diagnosed in athletes, the
      architecture and function of the foot should be examined. Foot structure was
      evaluated in 10 male and 14 female athletes. Based on this examination, the
      subjects were classified into three groups: pes planus, pes cavus, and pes
      rectus. While running, the plantar pressure pattern of these athletes was
      assessed with pressure-measuring insoles. Using these measurements, peak
      pressures and impulses were calculated for different foot anatomical locations.
      The plantar heel load was distributed significantly (P < 0.05) more toward the
      anterior part of the calcaneus in the pes planus group compared with the normal
      group. The relative load under the midfoot region was significantly (P < 0.05)
      lower in the pes cavus group compared with the other foot types. The relative
      load of the forefoot was significantly (P < 0.05) higher in the pes cavus group
      and lower in the pes planus group. Both feet of an athlete showed a similar
      plantar pressure pattern. Three successive steps were comparable in terms of
      impulses, but the peak pressures varied significantly from step to step. The
      local impulse and peak pressure values obtained in barefoot running differed
      significantly from the values obtained in running with sport shoes.

PMID- 8574375
TI  - Influence of arthrodeses on kinematics of the axially loaded ankle complex during
      dorsiflexion/plantarflexion.
AB  - The purpose of this study was to quantify the effect of selective arthrodesis
      (stabilization) of the ankle, subtalar, and talonavicular joints on the
      rotational movement of the tibia and the calcaneus occurring with
      dorsiflexion/plantarflexion. Six cadaver foot-leg specimens were investigated
      using an unconstrained testing apparatus. Simulated ankle joint arthrodesis
      caused a large increase in tibial rotation and calcaneal eversion-inversion.
      Subtalar and talonavicular stabilization did not cause as large a rotation.

PMID- 8574376
TI  - The long accessory flexor muscle: an anatomical study.
AB  - A total of 136 lower limbs from 68 human cadavers were dissected to determine the
      incidence of the long accessory flexor muscle and its origins and insertions. The
      muscle was present in 11 of 136 lower extremities (8%) and 9 of 68 cadavers
      (13%). Five long accessory flexor muscles originated from the tibia and fascia of
      the deep posterior compartment and six began on the fibula. All of the tendons
      were deep to the laciniate ligament and coursed within the tarsal tunnel. All
      five of the tendons originating from the tibia inserted on the quadratus plantae,
      with two of the tendons having an additional insertion on the flexor digitorum
      longus. Three of the tendons with fibular origin inserted on the quadratus
      plantae and three inserted on the flexor digitorum longus. The importance of the
      long accessory flexor muscle relates as a cause or association with tarsal
      tunnel.

PMID- 8574377
TI  - Comparative evaluation of bone suture anchor to bone tunnel fixation of tibialis
      anterior tendon in cadaveric cuboid bone: a biomechanical investigation.
AB  - A multiphase biomechanical study was performed using human tibialis anterior
      tendons and cuboid bones, comparing the fixation of the tendon to the bone using
      bone anchors and bone tunnels. Twenty-six specimens were tested for ultimate load
      to failure comparing Mitek Superanchor fixation with no. 1 and no. 5 braided
      polyethelyne suture to bone tunnel fixation. Mitek Superanchor with no. 5 suture
      failed at 223 N, compared with Mitek Superanchor with no. 1 suture at 134 N and
      bone tunnel at 143 N (P = 0.033). Mitek with no. 1 suture versus bone tunnel was
      not significantly different. The Mitek with no. 5 suture failed at the
      tendon/suture interface (75%), the Mitek with no. 1 suture failed at the
      suture/anchor interface (56%), and bone tunnel fixation failed most commonly by
      fracture of the tunnel (76%). This study is the first biomechanical analysis of
      the pullout strengths of bone tunnels or suture anchors in the cuboid bone. We
      have shown that the suture anchor has a pullout strength comparable or superior
      to a conventional bone tunnel in an in vitro situation. We believe it is a viable
      alternative to fixation of the tibialis anterior tendon to the cuboid when there
      is insufficient tendon length or failure of the bone tunnel.

PMID- 8574378
TI  - Accessory calcaneus: a case report and literature review.
AB  - A case of bilateral accessory calcanii is presented in which the accessory
      ossicle articulated with the talus and calcaneus at the lateral aspect of the
      posterior facet of the subtalar joint, causing premature subtalar degenerative
      changes in a 19-year-old man. Although rare and usually asymptomatic, accessory
      ossicles around the foot may need surgical excision if painful or if sufficient
      size is obtained to cause deformity and/or limitations in range of motion.

PMID- 8574379
TI  - Accessory soleus presenting as a posterior ankle mass: a case report and
      literature review.
AB  - The accessory soleus muscle is a rare anatomic variant that may present as a mass
      in the posterior-medial aspect of the ankle in young adults. The presence of such
      a mass may result in pain and difficulty with running. We present a case of
      accessory soleus muscle in a 21-year-old soldier and review the literature. We
      present the first magnetic resonance imaging studies in the American literature,
      to our knowledge, of this unusual anomaly.

PMID- 8574380
TI  - Monitoring recovery following syndesmosis sprain: a case report.
AB  - A sprain to the tibial-fibular syndesmosis often results in prolonged
      rehabilitation or surgical intervention before recovery occurs. This paper
      documents gait recovery both before and after surgery for a syndesmosis sprain.
      Ground reaction force (GRF) data were available before injury and before surgery.
      Data were also collected every 3 days from 4 days to 4 months after syndesmosis
      screw removal (8 weeks after surgery). Weightbearing during the stance phase of
      gait did not approach normal values until approximately 4 months after
      syndesmosis screw removal. The push-off phase of gait also was slow to recover.
      When it was possible for the subject to use one or two crutches, differences in
      GRF were evident, such that walking with one crutch demonstrated increased force
      production at the ground. Bracing the ankle with a semirigid brace increased GRF,
      whereas a boot-type lace-up brace resulted in decreased GRF. In this case report
      of a combined ankle and syndesmosis sprain, results suggest the weightbearing and
      push-off force were seriously compromised. Decreasing the number of walking
      assistive devices and wearing a semirigid ankle brace increased the amount of
      weightbearing through the affected leg and may have merit in encouraging muscle
      function.

PMID- 8574381
TI  - A method to facilitate translation of the chevron osteotomy.

PMID- 8574382
TI  - Therapeutic footwear for neuropathic ulcers.
AB  - Current literature on the treatment of patients with neuropathic ulcers generally
      does not fully consider pedorthic treatment. To evaluate pedorthic treatment of
      patients with neuropathic ulcers, an ongoing treatment and tracking program was
      developed. This program consisted of regularly scheduled visits, footwear
      inspections, and orthosis replacement, repair, or adjustment. Our intent is not
      to suggest that therapeutic footwear be used as a primary treatment to close foot
      ulcers, but to highlight the place of education, proper shoes, and orthosis in
      the healing process.

PMID- 8574383
TI  - 7th International Symposium on High Performance Capillary Electrophoresis.
      Wurzburg, Germany, 29 January-2 February 1995. Proceedings.

PMID- 8574384
TI  - Analysis of protein fractions by micropreparative capillary isoelectric focusing
      and matrix-assisted laser desorption time-of-flight mass spectrometry.
AB  - In this study, the use of capillary isoelectric focusing (cIEF) as a
      micropreparative tool for protein analysis by matrix-assisted laser desorption
      time-of-flight mass spectrometry (MALDI-TOF-MS) is demonstrated. A newly
      designed, automated, collection interface equipped with a fiber-optic UV detector
      and a sheath flow connection was employed for collection of protein fractions.
      Multiple fractions were collected during a single cIEF run and further analyzed
      by MALDI-TOF-MS for mass assignment. The feasibility of the method was tested
      with a mixture of model proteins with different isoelectric points and molecular
      masses, and with variants of human hemoglobins differing in pI, but with
      negligible difference in M(r). Some practical considerations of the collection
      procedure and subsequent TOF analysis are presented.

PMID- 8574385
TI  - Capillary zone electrophoresis at subzero temperatures. I. Separation of the cis
      and trans conformers of small peptides.
AB  - The cis-trans conformers of two dipeptides, Phe-Pro and Leu-Pro, and two opioid
      heptapeptides containing one or two proline residues were separated by capillary
      zone electrophoresis (CZE) in borate buffer at low temperatures down to -17
      degrees C. At temperatures near ambient, the relaxation time of the cis-trans
      isomerization is on the time-scale of minutes for the dipeptides and thus
      commensurate with the migration times in CZE under usual operating conditions.
      The conformers of both dipeptides could be separated with baseline resolution
      below 10 degrees C in neat aqueous 100 mM sodium borate (pH 8.4). The conformer
      peaks on the electropherograms were identified by using authentic samples of the
      cis and trans forms of Phe-Pro and Leu-Pro that were obtained by reversed-phase
      HPLC at 0 degree C, validated by NMR spectroscopy and stored in liquid nitrogen.
      The interplay of the electrophoretic migration and on-column isomerization
      reaction in CZE of Phe-Pro under various conditions was analyzed in the light of
      the Damkohler number (Da). The results showed that besides employing low
      temperature increasing the voltage and/or decreasing the capillary length also
      reduce the magnitude of Da to bring about the separation of interconverting
      species. In this work the use of low temperature in this work was preferred due
      to the experimental simplicity. The separation of cis-trans conformers of two
      opioid heptapeptides was carried out by CZE at subzero temperatures with aqueous
      sodium borate containing 23% (v/v) glycerol at pH* 11.3 as measured with a glass
      electrode. The two conformers of Tyr-Pro-Phe-Asp-Val-Val-Gly-NH2 were baseline
      separated at -12 degrees C and the four conformers of Tyr-Pro-Phe-Gly-Tyr-Pro-Ser
      NH2 due to the presence of two peptidyl-proline bonds in the molecule, were also
      resolved at -12 degrees C. From the electrophoretic mobilities, the hydrodynamic
      radii of the cis-trans conformers of the dipeptides Phe-Pro and Leu-Pro were
      estimated. In both cases, the trans isomers had 1.3 times greater Stokes radii
      than the cis conformers. This agrees with the observed migration order and
      molecular modeling results. The hydrodynamic radii of the Phe-Pro conformers were
      smaller than those of the Leu-Pro isomers despite the lower molecular mass of the
      latter. The results demonstrate that CZE is suitable for measuring certain
      molecular properties and suggest that the methods introduced here are applicable
      to the study of other systems of interconverting conformers.

PMID- 8574386
TI  - Analysis by capillary electrophoresis-laser-induced fluorescence detection of
      oligosaccharides produced from enzyme reactions.
AB  - Six structurally similar, fluorescently labeled oligosaccharides were baseline
      resolved by capillary electrophoresis (CE); laser induced fluorescence (LIF)
      detection gave detection limits of 50 molecules for the oligosaccharides. A
      simple design of the LIF detector that incorporates the advantages of high
      sensitivity, stability and ease of operation is described. The system was used to
      monitor enzyme products formed during the incubation of yeast cells with alpha-D
      Glc(1-->2)alpha-D-Glc(1-->3)alpha-D-glc-O(CH2)8CONHCH2CH2NHCO -
      tetramethylrhodamine. This fluorescent trisaccharide is enzymatically hydrolyzed
      to fluorescent disaccharide, monosaccharide and the free linker arm that is used
      to conjugate the saccharides with the fluorophore tetramethylrhodamine.

PMID- 8574387
TI  - Separation of 8-aminonaphthalene-1,3,6-trisulfonic acid-labelled neutral and
      sialylated N-linked complex oligosaccharides by capillary electrophoresis.
AB  - Complex oligosaccharides, both neutral and sialylated, were derivatized with 8
      aminonaphthalene-1,3,6-trisulfonic acid (ANTS) and separated by capillary
      electrophoresis. The derivatization reaction was carried out in a total reaction
      volume of 2 microliters. The separated peaks were detected by laser-induced
      fluorescence detection using the 325-nm line of a He-Cd laser. Concentration and
      mass detection limits of 5 x 10(-8) M and 500 amol, respectively, could be
      achieved. The limiting step for higher sensitivity is not the detector
      performance, however, but the chemistry with a derivatization limit of 2.5 x 10(
      6) M. Two labelling protocols were established, one with overnight reaction at 40
      degrees C and the other with a 2.5-h derivatization time at 80 degrees C. Neutral
      oligosaccharides could be labelled with either protocol. However, sialylated
      oligosaccharides hydrolysed when labeled at 80 degrees C. Low nanomole to
      picomole amounts of oligomannose-type and complex-type oligosaccharide mixtures
      were derivatized and separated in less than 8 min with excellent resolution using
      a phosphate background electrolyte at pH 2.5. The linear relationship between the
      electrophoretic mobility and the charge-to-mass ratios of the ANTS conjugates was
      used for peak assignment. Further, the influence of the three-dimensional
      structure of the complex oligosaccharides on their migration behaviour is
      discussed. The suitability of the ANTS derivatization and the subsequent
      separation for the analysis of complex oligosaccharide patterns is demonstrated
      with oligosaccharide libraries derived from ovalbumin and bovine fetuin. For peak
      assignment the patterns are compared with those of the oligomannose and the
      complex-type oligosaccharide mixtures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574388
TI  - Capillary zone electrophoresis of organic acids in serum of critically ill
      children.
AB  - Capillary zone electrophoresis with indirect UV detection was found to be
      suitable for the determination of organic acids in serum. Serum can be analysed
      directly without any deproteination in a capillary coated with linear
      polyacrylamide. With 10 mM epsilon-aminocaproic acid-10 mM mandelic acid (pH 3.8)
      as the operational electrolyte, anions such as pyruvate, phosphate, citrate,
      malate, acetoacetate and lactate can be determined in 12 min. In quantitative
      analysis, the calibration line for lactate is linear over the range 0-10 mM. The
      detection limit for citrate was 8 microM. The effect of the chloride
      concentration on the migration times of minor peaks is discussed. The potential
      of the method was demonstrated by analysing sera from several critically ill
      children.

PMID- 8574389
TI  - Capillary electrophoretic methods for a clear identification of selenoamino acids
      in complex matrices such as human milk.
AB  - Selenoamino acids from size-exclusionchromatographic fractions of human milk were
      identified and determined by capillary electrophoresis (CE). For this purpose,
      different CE methods were developed to separate these selenoamino acids from
      other molecules with similar molecular masses. Methods were introduced for the
      clear identification of the analytes. These methods were designed to allow the
      identification of selenoamino acids in spite of the presence of many molecules
      with similar mobilities. Further, they overcome identification problems caused by
      shifts of migration times (due to different ionic compositions) compared with
      standard solutions.

PMID- 8574390
TI  - Inhibition of dipeptidyl peptidase IV (DP IV) by anti-DP IV antibodies and non
      substrate X-X-Pro- oligopeptides ascertained by capillary electrophoresis.
AB  - Dipeptidyl peptidase IV (DP IV)-catalyzed hydrolysis of the NH2-X-Pro-containing
      N-terminal dodecapeptide of IL-2 was studied using free zone capillary
      electrophoresis as an alternative peptidase assay. In contrast to the
      conventional DP IV substrate glycyl-prolyl-p-nitroanilide (Gly-Pro-pNA), the
      hydrolysis of this peptide by DP IV was found to be significantly inhibited by
      anti-DP IV antibodies. Inhibition of DP IV was also observed with a number of non
      substrate oligopeptides containing an N-terminal X-X-Pro- structure, including
      the HIV Tat protein. For Met-IL-2(1-6), we determined a competitive inhibition
      with an inhibition constant of ca. 100 microM.

PMID- 8574391
TI  - Studies of complexes between proteases, substrates and the protease inhibitor
      alpha 2-macroglobulin using capillary electrophoresis with laser-induced
      fluorescence detection.
AB  - Capillary zone electrophoresis (CZE) with laser-induced fluorescence (LIF)
      detection is shown to constitute a unique technique for the investigation of the
      interaction between proteases, protease inhibitors and substrates. Under
      optimized analysis conditions, the formation of a complex between FITC-labelled
      proteases such as trypsin, plasmin, alpha-chymotrypsin and the (unlabelled)
      protease inhibitor alpha 2-macroglobulin was studied. This is not possible with
      UV detection, since under such conditions the complex cannot be distinguished
      from the unreacted protease inhibitor. Low ratios of FITC bonded to the proteases
      further complex formation, while high ratios often prevent the reaction. Complex
      formation shows a strong dependence on the incubation conditions (pH, salt
      concentration, temperature, incubation time). Once formed, however, the complexes
      are stable under CZE conditions (e.g., a pH of the electrophoresis buffer of
      10.5) for at least 30 min. Treatment with sodium dodecyl sulfate (5 min at 90
      degrees C or 30 min at 75 degrees C) does not destroy the complexes, whereas
      treatment with mercaptoethanol (reduction of disulfide bonds) eliminates the peak
      from the electropherogram. Both findings argue for the formation of a covalent
      bond between the protease and the inhibitor during complex formation. Since the
      reaction of the proteases with alpha 2-macroglobulin does not involve the binding
      site of the former, a residual proteolytic activity is still observed in the
      ensuing complex. The extent of the inhibition of the remaining trypsin activity
      in a trypsin--alpha 2-macroglobulin complex was established to depend on the
      molecular mass of the second trypsin inhibitor.

PMID- 8574392
TI  - Evaluation of an optically active crown ether for the chiral separation of di-
      and tripeptides.
AB  - The direct optical resolution of a number of di- and tripeptides was achieved by
      capillary zone electrophoresis using an enantioselective crown ether as buffer
      additive. The protonated primary amines form inclusion complexes with the crown
      ether. Chiral resolution is based on different stability constants of the
      diastereomeric complexes thereby changing the electrophoretic mobilities of the
      enantiomers. Enantioselectivity is strongly affected by the distance between the
      amine functionality and the chiral carbon atom. This effect was studied using di-
      and tripeptides especially synthesized for this purpose. In general, baseline
      resolution was obtained for those peptides with the amine group located as far as
      four bonds from the stereogenic center. Additionally, tripeptides possessing two
      chiral centers were separated to investigate the potential of the chiral selector
      for the analysis of complex analytes with related structures. Experimental
      factors such as crown ether concentration, buffer pH and temperature also show a
      strong influence on the resolution. These factors can be successfully employed
      for method optimization.

PMID- 8574393
TI  - Determination of alpha-difluoromethylornithine in blood by microdialysis sampling
      and capillary electrophoresis with UV detection.
AB  - A procedure is described for the analysis of alpha-difluoromethylornithine
      (DFMO), an anti-cancer agent, in plasma microdialysis (MD) samples. DFMO has been
      shown to be effective alone or in combination with other agents in the treatment
      of several cancers. Precolumn derivatization of DFMO with naphthalene-2,3
      dicarboxaldehyde-cyanide (NDA-CN) in pH 10.0 borate buffer results in the rapid
      formation of a stable mono-derivatized product (N-substituted 1
      cyanobenz[f]isoindole, CBI), which is UV active. An analytical method has been
      developed to separate CBI-DFMO from NDA-CN derivatization products of 20 standard
      amino acids using capillary electrophoresis (CE). This method is then employed
      for the determination of DFMO in plasma microdialysis samples. Separation of DFMO
      from other components in the dialysate was achieved within 20 min. The response
      for DFMO in Ringer's solution was linear over the range of 1.2 x 10(-6) to 1.6 x
      10(-4) M after derivatization. The detection limit of DFMO in the plasma
      dialysate is 5 microM using UV detection at 254 nm. This method has been proven
      to have adequate sensitivity for quantitation of DFMO in i.v. microdialysate
      samples and has been successfully applied to monitoring the pharmacokinetics of
      DFMO by CE-UV.

PMID- 8574394
TI  - Capillary zone electrophoretic resolution of recombinant human bone morphogenetic
      protein 2 glycoforms. An investigation into the separation mechanisms for an
      exquisite separation.
AB  - Recombinant human bone morphogenetic protein 2 (rhBMP-2) is a disulfide-linked
      homodimeric glycoprotein (M(r) = 30,000) which induces bone formation in vivo in
      several animal model systems. In this paper, we report the separation of a
      homogeneous rhBMP-2 sample into nine peaks by capillary zone electrophoresis
      (CZE), using a simple, pH 2.5, phosphate buffer containing no additives. The nine
      peaks have been identified to be glycoforms of rhBMP-2 [designated as (rhBMP-2)2
      (GlcNAc)4(ManZ), where Z varies from 10 to 18]. The difference between any
      adjacent pair of peaks is only one mannose residue (M(r) = 162). The ability of
      CZE to resolve rhBMP-2 glycoforms having the same charge and differing only 0.5%
      in molecular mass, without resorting to chemical complexation, is both unexpected
      and intriguing. Possible mechanisms explaining how the additional mannose can
      affect the mobility of rhBMP-2 glycoforms were explored. Zeta potentials of
      various glycoforms were calculated from their mobilities and interpreted in light
      of diffuse double layer parameters. Our results suggest that CZE employing a low
      pH buffer, where proteins are highly charged, may be uniquely suitable for
      complex protein glycoform analysis.

PMID- 8574395
TI  - Gene cassettes: a new class of mobile element.

PMID- 8574396
TI  - Mycobacterium smegmatis DNA gyrase: cloning and overexpression in Escherichia
      coli.
AB  - The cloning and characterization of DNA gyrase genes from Mycobacterium smegmatis
      is described. The DNA sequence of 5119 bp encoding both gyrB and gyrA genes was
      determined. The gene gyrB precedes gyrA with a short intergenic region of 29
      nucleotides. The proteins encoded, GyrB and GyrA, exhibit 45-80% identity to
      gyrase polypeptides from other bacteria. The genes were further engineered for
      overexpression in Escherichia coli. Both genes were individually cloned into a
      phage T7 expression system and overexpressed. The expressed GyrB and GyrA
      proteins had molecular masses of 75 and 95 kDa, respectively, in agreement with
      that calculated from the ORFs. The extracts from the overexpressing clones were
      fractionated to enrich the subunits and assayed for enzyme activity. While the
      individual extracts showed no detectable activity, the combined extract exhibited
      a strong DNA supercoiling activity. This activity was ATP-dependent and
      novobiocin-sensitive. The identity of the genes was also confirmed by
      complementation analysis.

PMID- 8574397
TI  - Role of the viaB locus in synthesis, transport and expression of Salmonella typhi
      Vi antigen.
AB  - The Vi antigen is a capsular polysaccharide expressed by Salmonella typhi, the
      agent of human typhoid fever. Expression of this antigen is controlled by the
      viaA and viaB chromosomal loci. The viaB locus is composed of 11 genes designated
      tviA-tviE (typhi Vi), vexA-vexE (Vi antigen export) and ORF11. We constructed S.
      typhi Ty2 strains carrying non-polar mutations in ten genes located at the viaB
      locus and examined the individual contribution of each gene to Vi phenotype.
      Phenotypes of the mutants and complementation experiments suggested that
      synthesis of Vi antigen monomer was catalysed by the TviB and TviC polypeptides.
      Subsequent polymerization of the polysaccharide might be catalysed by the TviE
      protein, but required functional TviD product. Proteins encoded by vexA, vexB and
      vexC directed transport of the polymer to the bacterial cell surface. Anchoring
      of the Vi antigen at the bacterial cell surface was dependent of the VexE
      protein. The TviA protein was not essential for Vi polymer synthesis. However,
      disruption of the tviA gene on S. typhi Ty2 chromosome strongly decreased
      expression of Vi antigen. This defect was fully complemented by providing tviA in
      trans on a recombinant plasmid. By using lacZ transcriptional fusions, it was
      shown that the TviA product positively regulated co-transcription of the tviA and
      tviB genes from a promoter located upstream of tviA. Moreover, we showed that a
      tviAB-lacZ fusion was not expressed in a viaA (rcsB) mutant of S. typhi.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8574398
TI  - The cyanobacterium Synechococcus sp. strain PCC 7942 contains a second alkaline
      phosphatase encoded by phoV.
AB  - A gene (phoV) encoding an alkaline phosphatase from Synechococcus sp. strain PCC
      7942 was isolated by screening a plasmid gene bank for expression of alkaline
      phosphatase activity in Escherichia coli JM103. Two independent clones carrying
      the same alkaline-phosphatase-encoding gene were isolated. One of these clones
      (pKW1) was further analysed and the nucleotide sequence of a contiguous 3234 bp
      DNA fragment was determined. Two complete open reading frames (ORF1 and phoV) and
      an incomplete ORF3 were identified reading in the same direction. The deduced
      phoV gene product showed 34% identity to the alkaline phosphatase PhoA from
      Zymomonas mobilis, and the N-terminal part of the putative ORF3 protein exhibited
      57% identity to a protein of unknown function from Frankia sp. Insertional
      inactivation of the Synechococcus PCC 7942 phoV gene failed, indicating an
      essential role for either the phoV or the ORF3 gene product. PhoV consists of 550
      amino acid residues, resulting in a molecular mass of 61.3 kDa. To overexpress
      the Synechococcus PCC 7942 phoV gene in E. coli, plasmid pKW1 was transformed
      into a phoA mutant of E. coli (CC118). In E. coli strain CC118(pKW1) PhoV was
      expressed constitutively with high rates of activity, and was shown to be
      membrane associated in the periplasmic space. After partial purification of the
      recombinant PhoV, it was shown that, like other alkaline phosphatases, the
      Synechococcus PhoV had a broad pH optimum in the alkaline region and a broad
      substrate specificity for phosphomonoesters, required Zn2+ for activity, and was
      inhibited by phosphate. In contrast to several other alkaline phosphatases, PhoV
      was inhibited by Mn2+. Due to the lack of a Synechococcus PCC 7942 phoV mutant
      strain, the function of PhoV remains uncertain. However, the present results show
      that Synechococcus PCC 7942 has a second, probably phosphate-irrepressible,
      alkaline phosphatase (PhoV, 61.3 kDa) in addition to the phosphate-repressible
      enzyme (PhoA, 145 kDa) already described.

PMID- 8574399
TI  - Two genes encoding the beta-galactosidase of Lactobacillus sake.
AB  - The beta-galactosidase of Lactobacillus sake DSM 20017 is encoded by two genes
      located on its chromosome. These genes designated lacL and lacM were cloned in
      Escherichia coli NM 554 on an 8.65 kbp HindIII fragment inserted in vector
      pRB473. Deletion analysis of the originally cloned fragment revealed that both
      genes are required for the formation of a functional beta-galactosidase. lacL and
      lacM are transcribed as a single transcript of approximately 2.9 kbp starting 34
      bp upstream of the translational start codon. The proteins derived from lacL and
      lacM share only 18-59% homology with other beta-galactosidases. The genes
      encoding the beta-galactosidase are scattered with multiple direct and inverted
      repeats of 9-12 bp. However, comparison with the plasmid-encoded Leuconostoc
      lactis beta-galactosidase revealed equal distribution of conserved amino acid
      residues and suggests that the genes have a common origin. Specific deletions or
      insertions resulting from the presence of the repeats were not observed. The L.
      sake beta-galactosidase was phenotypically expressed in E. coli NM 554 and
      Lactobacillus curvatus LTH 1432. Its two genes can be used to replace antibiotic
      reporter genes to develop food-grade vectors and alpha-complementation systems
      for self-cloning in meat lactobacilli.

PMID- 8574401
TI  - Multiple cysteine proteinases of the pathogenic protozoon Tritrichomonas foetus:
      identification of seven diverse and differentially expressed genes.
AB  - The cattle protozoan parasite Tritrichomonas foetus has multiple forms of
      cysteine proteinases. To investigate their diversity, PCR and reverse
      transcriptase PCR were used to isolate genomic DNA and cDNA fragments,
      respectively, encoding different cysteine proteinases. Seven genes have been
      identified, TFCP3-6 from amplification of genomic DNA and TFCP7-9 from
      amplification of cDNA. Comparison of the predicted amino acid sequences indicates
      that the T. foetus enzymes are cathepsin-L-like rather than cathepsin-B-like in
      structure. However, there is considerable diversity among the proteinases. TFCP7
      and TFCP8 are most similar to one another (78% identity), while TFCP3 and TFCP9
      are the least closely related (30% identity). All but one of the genes are single
      copy, the exception being TFCP3, which was present in multiple copies in one of
      the three isolates examined. Single transcripts were detected for each of the
      seven genes. TFCP8 was expressed at the highest levels, while transcripts for
      TFCP4 were only just detectable. In T. foetus F2, the strain from which the
      genomic DNA and mRNA were isolated, transcripts of the five other genes were
      present at intermediate levels. When two other isolates were compared with F2,
      differences in the expression of individual genes were apparent, with either one
      or two of them not expressed. In spite of these differences the major cysteine
      proteinases detected in the three isolates using substrate-SDS-PAGE appeared
      identical. The data show that the multiplicity of cysteine proteinases in T.
      foetus is due, in part at least, to the presence of multiple genes and that some
      of the genes encode cysteine proteinases which are not among the high-activity
      enzymes detected previously.

PMID- 8574400
TI  - An X-prolyl dipeptidyl aminopeptidase (pepX) gene from Lactobacillus helveticus.
AB  - The X-prolyl dipeptidyl aminopeptidase gene (pepX) of an industrially used
      Lactobacillus helveticus strain has been detected by nucleic acid hybridization,
      cloned, characterized and sequenced. One ORF of 2379 bp with coding capacity for
      a 90.6 kDa protein (PepX) was found. The ORF was preceded by a typical
      prokaryotic promoter region. An inverted repeat structure with delta G of -84.1
      kJ mol-1 was found downstream of the coding region. The deduced amino acid
      sequence of the 90.6 kDa protein showed 49.3, 49.4 and 77.7% homology with the
      PepX proteins from Lactococcus lactis subsp. lactis, Lc. lactis subsp. cremoris
      and Lactobacillus delbrueckii subsp. lactis, respectively. Northern blotting
      revealed a 2.6 kb transcript and one transcription start site was identified via
      primer extension analysis using an A.L.F. sequencer. In a bioreactor study, the
      expression of pepX in Lb. helveticus was studied as a function of growth.
      Transcription of pepX was typical of exponential growth phase expression. The
      pepX gene has been cloned into pKK223-3 and expressed at a high level in
      Escherichia coli JM105. PepX was purified to homogeneity by ion-exchange and
      hydrophobic interaction chromatography. Optimum PepX activity was observed at pH
      6.5 and 45 degrees C. According to gel filtration analysis, PepX is a dimer of
      165 kDa. The enzyme was inactivated by heavy metal ions such as Cu2+, Cd2+ and
      Zn2+. EDTA and 1,10-phenanthroline did not decrease PepX activity significantly.
      It was completely inhibited by p-hydroxymercuribenzoate and reactivated by adding
      DTT, and strongly inhibited by PMSF. PepX is thus a metal-independent serine
      peptidase having functional sulfhydryl groups at or near the active site.

PMID- 8574402
TI  - Capnocytophaga gingivalis aminopeptidase: a potential virulence factor.
AB  - The production and properties of an aminopeptidase from Capnocytophaga gingivalis
      were studied. C. gingivalis was grown in continuous culture over a range of
      dilution rates and the cell-bound and extracellular levels of aminopeptidase and
      trypsin-like protease (TLPase) measured. At high growth rates (0.6 mu rel) TLPase
      specific activity was low and found exclusively as cell-bound activity; at low
      growth rates (0.0375 mu rel), specific activity was high and 26% was found as
      extracellular activity. In contrast, aminopeptidase specific activity was highest
      at 0.3 mu rel and the ratio of cell-bound to extracellular activity was
      relatively constant at all growth rates. Only about 5% of the total activity was
      extracellular. The aminopeptidase, which has a wide specificity towards
      artificial substrates, was purified to homogeneity, as judged by SDS-PAGE, from
      the supernatant fluid of cells grown in continuous culture in a
      tryptone/glucose/thiamine medium. The enzyme has a molecular mass of 61 kDa, a pl
      of 6.3, a pH optimum close to 7.5 and showed a requirement for magnesium or
      calcium ions. The N-terminal sequence of the first 10 amino acids (Asp-Val-Asn
      Met-Leu-Trp-Tyr-Val-x-Arg...) showed no similarity to any published sequence.
      This enzyme in its cell-bound or extracellular form may be important in the
      nutrition and pathogenesis of C. gingivalis in the human oral cavity.

PMID- 8574403
TI  - The physiology of erythromycin biosynthesis in cyclic fed batch culture.
AB  - Antibiotic production in Saccharopolyspora erythraea was significantly enhanced
      in cyclic fed batch culture (c.f.b.c) compared to batch culture, whereas
      chemostat culture resulted in reduced production. C.f.b.c. allowed the specific
      growth rate to be varied, with time, according to an asymptotically decreasing
      trajectory without the necessity for nutrient exhaustion. It was, therefore,
      possible to increase productivity by increasing the growth-limiting substrate
      concentration. It was necessary to apply the c.f.b.c. regime to early-exponential
      phase cultures in order to obtain a stable, nutrient-limited, c.f.b.c. The
      antibiotic production rate during any c.f.b.c. cycle was dependent on the
      relationship between the specific growth rate at the time and the growth rate at
      the start of the cycle.

PMID- 8574404
TI  - Acetyl-CoA carboxylase activity in Helicobacter pylori and the requirement of
      increased CO2 for growth.
AB  - A biotinylated acetyl-CoA carboxylase from the microaerophilic bacterium
      Helicobacter pylori was partially purified and characterized. The approximate
      molecular mass of the native enzyme was estimated at 235 kDa by native PAGE. A
      single band corresponding to approximately 24 kDa was detected by SDS-PAGE,
      suggesting that the native enzyme is a multi-protein complex. The protein was
      isolated from the soluble fraction of the cell. Catalytic activity was acetyl-CoA
      dependent and inhibited by avidin but unaffected by avidin pretreated with excess
      biotin. The end-product of the reaction was identified as malonyl-CoA and the
      reaction was shown to be reversible by NMR spectroscopy. The activity of the
      enzyme was 0.29 mumol min-1 (mg protein)-1. The Vmax for bicarbonate was
      calculated at 0.73 mumol min-1 (mg protein)-1, and the affinity of the enzyme for
      this substrate was relatively low, with an apparent Km of 16.6 mM. These data
      provide the first evidence of a possible physiological role for the requirement
      of high levels of CO2 for growth in vitro of this bacterium.

PMID- 8574405
TI  - Starvation yields a drastic decrease in outer-membrane permeability to a
      periplasmic foreign protein in Myxococcus xanthus.
AB  - A recombinant Myxococcus xanthus strain was constructed that constitutively
      produces two proteins from Escherichia coli, the cytoplasmic beta-galactosidase
      and the periplasmic pH 2.5 acid phosphatase (AppA protein). We have previously
      shown that during vegetative growth, AppA protein is partly accumulated in the
      periplasm of M. xanthus and partly released into the medium. We demonstrate here
      that during starvation-induced development, release of periplasmic AppA protein
      to the medium did not occur over a period of 20 h. This was coincident with, but
      not caused by, the arrest of the synthesis of the foreign proteins. We have shown
      that this lack of secretion could be attributed to starvation per se and did not
      depend on the ability of the cells to undergo development. Our findings suggest
      that protein secretion which occurs during the first hours of starvation-induced
      development might therefore take place via a different route from that which
      occurs in vegetative cells.

PMID- 8574406
TI  - Adaptive response of Schizosaccharomyces pombe to hydrogen peroxide and
      menadione.
AB  - The response of Schizosaccharomyces pombe to oxidative stresses has been
      examined. On challenging Schiz. pombe for 60 min at early exponential phase with
      either 40 mM H2O2 or 6 mM menadione (MD), a superoxide-generating agent, less
      than 10% of the cells survived. Pretreating Schiz. pombe cells with 0.2 mM H2O2
      or 0.2 mM MD for 1 h significantly increased survival of these lethal doses of
      each oxidant, indicating the existence of an adaptive response to oxidative
      stress. Furthermore, cells pretreated with a low dose of MD became resistant to a
      lethal dose of H2O2. However, cells pretreated with H2O2 became only partially
      resistant to a lethal dose of MD. Adaptation was accompanied by the induction of
      several oxidative defence enzymes. The presence of 0.2 mM H2O2 induced catalase
      by 2.8-fold and peroxidase by 2.0-fold The presence of 0.2 mM MD induced catalase
      by 2.0-fold, glucose-6-phosphate dehydrogenase by 1.9-fold, glutathione reductase
      by 2.7-fold, peroxidase by 3.0-fold, and superoxide dismutase (SOD) by 2.1-fold.
      The higher induction of these defence enzymes by MD may explain why MD-pretreated
      cells were better adapted to lethal doses of oxidants than H2O2-pretreated ones.
      All these enzymes except SOD and peroxidase increased more than 5.0-fold as cells
      proceeded into stationary phase. The GSH/GSSG ratio also increased by 60%. These
      changes accord with the observation that stationary phase cells survive oxidant
      treatment better than cells in vegetative growth.

PMID- 8574407
TI  - The tellurite-resistance determinants tehAtehB and klaAklaBtelB have different
      biochemical requirements.
AB  - The tehAtehB operon from the Escherichia coli chromosome (32.3 min) mediates
      resistance to potassium tellurite (K2TeO3) when expressed on a multicopy plasmid
      such as pUC8 (pTWT100). An MIC of 128 micrograms ml-1 is observed when tehAtehB
      is expressed in a wild-type host and grown on rich media. In this study, the
      tehAtehB determinant was transformed into mutants deficient in electron transport
      processes and/or thiol redox coupling within E. coli. These mutants included ubi,
      nad, cys, nar, trx, grx, gsh and sod. MICs of tehAtehB transformed into these
      mutants ranged from 1-16 micrograms K2TeO3 ml-1 compared to 0.03-2 micrograms ml
      1 for strains transformed with a control plasmid. The tellurite-resistance
      determinant locus kilA cloned from the IncP alpha plasmid RK2Ter (pDT1558) was
      also investigated in these strains. This tellurite-resistance determinant showed
      little or no dependency on the host genotype. The ability of tehAtehB to mediate
      resistance in wild-type hosts is limited to rich medium. Rich medium may provide
      a key unidentified cofactor required by TehATehB that is not provided under
      minimal conditions. Again, the ability of the kilA determinant to mediate
      tellurite resistance was independent of medium conditions. These data suggest
      that either a reducing environment or electron-reducing equivalents are required
      for tehAtehB to mediate high levels of resistance to potassium tellurite.
      Therefore, the two resistance determinants studied here possess two very
      different biochemical mechanisms of resistance. Our data also suggest a mechanism
      for endogenous resistance to tellurite which involves nitrate reductase,
      superoxide dismutase, and thiol redox processes.

PMID- 8574408
TI  - The GTP-binding protein G alpha s is present in dormant spores and expressed
      differentially during spore germination of the fungus Phycomyces blakesleeanus.
AB  - A DNA sequence homologous to a G alpha s DNA probe, and the corresponding G alpha
      s protein (stimulatory alpha-subunit of GTP-binding protein) were detected in
      Phycomyces blakesleeanus. The protein was demonstrated in membrane fractions of
      dormant spores of this fungus using three different experimental approaches.
      Photoaffinity-labelling experiments with [alpha-32P]GTP of the membrane fraction
      revealed two bands, of 56 and 32 kDa. The 56 kDa GTP-binding protein was detected
      by this method in all the stages of early development and growth investigated.
      Also, a spore protein of 56 kDa was ADP-ribosylated by cholera toxin, and a 56
      kDa protein was detected by Western blotting with a specific antibody against
      mammalian G alpha s. These results indicate that G alpha s (56 kDa) is present in
      dormant spores of P. blakesleeanus. Using the ADP-ribosylation and Western
      blotting assays, G alpha s was detected during all stages of spore germination
      before the hyphae became highly branched, but it was not detected in the branched
      hyphae that formed 18 h after the initiation of spore germination. Therefore, G
      alpha s is expressed differentially during Phycomyces development.

PMID- 8574409
TI  - Phase and electron microscopic observations of osmotically induced wrinkling and
      the role of endocytotic vesicles in the plasmolysis of the Gram-negative cell
      wall.
AB  - When a Gram-negative bacterium is challenged with a sufficient concentration of a
      non-penetrating solute such as sucrose, water is sucked out of the cell.
      Plasmolysis spaces may form if the cell's cytoplasmic membrane (CM) separates
      from the murein wall (M) and the outer membrane (OM). However, we suggest that
      first wrinkling of the wall envelope, forced by dehydration of the cytoplasm,
      occurs. The cryofixation, freeze-substitution electron microscope studies used
      here are much too slow to study the kinetics of shrinkage, wrinkling and
      plasmolysis. However, they are consistent with faster phase microscope studies
      and previous stopflow experiments. For the electron microscopy studies reported
      here, only sucrose was used as the osmotic agent and under conditions that do not
      cause extreme plasmolysis. Plasmolysis spaces were associated with the formation
      of small membrane-bound vesicles in the nearby cytoplasm. Such vesicles formed by
      osmotic challenge are called 'endocytotic' in plant cell systems. They had been
      recorded in earlier plasmolysis studies in bacteria, but not interpreted as a
      concomitant part of plasmolysis space formation in certain locations of the cell.
      We suggest that the endocytotic vesicles form because the phospholipid membranes
      are capable of very little contraction so extra membrane must be disposed of when
      plasmolysis spaces form. In the case of plasmolysis spaces forming at poles and
      constriction sites, for geometric reasons the surface area of the CM may be
      conserved without disposition of excess membrane. We suggest that it is this
      biophysical property of lipid membranes that leads to the frequent formation of
      plasmolysis spaces at a pole and at the site of future division. We also observed
      a novel structure, this is seen only under mild osmotic up-shock, and consists of
      very thin, straight, uniform and long plasmolysis spaces which were called
      'lamellar spaces'; these commonly formed inside the sidewalls and were usually
      associated with the formation of endocytotic vesicles. Since lipoprotein links
      the M to the OM layers and thus could affect plasmolysis, we examined both wild
      type and deficient strains. Some effects were observed, but they were minimal.
      The volume of the periplasmic space of growing unshocked cells was determined to
      be about 7%.

PMID- 8574410
TI  - Enterochelin acquisition in Campylobacter coli: characterization of components of
      a binding-protein-dependent transport system.
AB  - Siderophore-mediated iron uptake systems play a central role in the pathogenesis
      of infection for many bacterial pathogens. Campylobacter species are not thought
      to produce siderophores, yet they are able to utilize both ferrichrome and
      enterochelin as sources of iron. Part of an operon named ceuBCDE, encoding
      components of a periplasmic binding-protein-dependent transport (PBT) system for
      the uptake of a ferric siderophore from Campylobacter coli, was cloned directly
      into Escherichia coli using a plasmid rescue technique. Phenotypic and genetic
      analyses of this system showed it to comprise two hydrophobic integral membrane
      proteins, CeuB (35.5 kDa) and CeuC (34.8 kDa), which may form the cytoplasmic
      membrane permease, an ATP-binding protein, CeuD (28.8 kDa), and a periplasmic
      substrate-binding protein, CeuE (34.5 kDa). In vivo labelling studies using
      [3H]palmitate demonstrated that CeuE, the periplasmic binding protein, is
      expressed as a lipoprotein in C. coli, which is unusual for a Gram-negative PBT
      system. Mutants of C. coli, defective in components of the transport mechanism,
      were severely impaired in the ability to utilize enterochelin as an iron source
      suggesting that this siderophore is a substrate for the transport system. This is
      the first molecular characterization of a PBT system in Campylobacter species.

PMID- 8574411
TI  - A Bordetella pertussis fepA homologue required for utilization of exogenous
      ferric enterobactin.
AB  - The bfeA (Bordetella ferric enterobactin) receptor gene was cloned from a
      Bordetella pertussis chromosomal library by using a screen in Escherichia coli to
      detect iron-repressed genes encoding exported proteins translationally fused to
      the E. coli phoA gene. The bfeA gene encoded a protein with a molecular mass of
      approximately 80 kDa and about 50% amino acid sequence identity to both the fepA-
      and pfeA-encoded enterobactin receptors of E. coli and Pseudomonas aeruginosa,
      respectively. Enterobactin prepared from iron-starved E. coli cultures supported
      growth of B. pertussis and Bordetella bronchiseptica in the presence of the iron
      chelator ethylenediamine-di-(o-hydroxyphenylacetic acid) (EDDA). Expression of
      the bfeA gene was induced by low iron availability, and iron-regulated expression
      appeared to be dependent upon the presence of the sequence contained within 370
      bp upstream of the bfeA structural gene. An internal fragment of the bfeA
      structural gene and flanking regions were shown by Southern analysis to be highly
      conserved among Bordetella species. Insertional inactivation of bfeA in both B.
      pertussis and B. bronchiseptica greatly impaired their ability to grow in the
      presence of enterobactin and EDDA. These findings suggest that enterobactin
      produced by other respiratory flora could aid in the colonization of the
      respiratory tract by Bordetella species.

PMID- 8574412
TI  - Major membrane proteins and lipoproteins as highly variable immunogenic surface
      components and strain-specific antigenic markers of Mycoplasma arthritidis.
AB  - Surface antigenic variation was investigated in Mycoplasma arthritidis, an agent
      that produces chronic arthritis in rats which shares several features with many
      mycoplasma-induced diseases and thus defines a well-characterized model system.
      Hyperimmune rabbit antisera (anti-ISR1, anti-PG6, anti-H606 and anti-158p10) to
      whole M. arthritidis organisms were used as immunological probes in Western
      immunoblots of four M. arthritidis prototype strains (ISR1, PG6, H606 and D263)
      and five rat-passaged substrains (ISR1p1, ISR1p7, ISR1p8, 158p10 and D263p1).
      Several prominent antigens were identified that varied in expression. By Triton X
      114 phase fractionation and treatment of whole cells with trypsin and
      carboxypeptidase Y, these strain-variant antigens were shown to be integral
      membrane proteins with C-termini and portions of the polypeptide chains oriented
      outside the membrane. Western blot immunoscreening of a large number of randomly
      selected clonal isolates and well-established clonal lineages from stock cultures
      of M. arthritidis ISR1p7, 158p10, PG6 and H606 revealed an expanded repertoire of
      variant membrane proteins whose expression was subject to independent, reversible
      phase variation. Colony immunoblots of these clonal populations with a
      hyperimmune rabbit antiserum to a gel-purified variant membrane protein (P36)
      showed that this phase switching occurred at a high frequency (10(-4) to 10(-2)
      per generation). Detailed immunological and biochemical characterization of the
      phase-variant membrane proteins demonstrated that they are: (i) antigenically
      related or distinct; (ii) apparently specific to particular strain populations;
      (iii) proteins or lipoproteins; (iv) major immunogens of M. arthritidis,
      recognized by serum antibodies from convalescent rat; and (v) able to undergo
      variation in expression during in vivo passage. Thus, M. arthritidis possesses a
      complex system capable of creating large repertoires of cell surface phenotypes
      which may affect the multiple interactions of this organism with its host and
      dictate its potential as a successful infectious agent and pathogen.

PMID- 8574413
TI  - Insertion element IS1296 in Mycoplasma mycoides subsp. mycoides small colony
      identifies a European clonal line distinct from African and Australian strains.
AB  - Strains of Mycoplasma mycoides subsp. mycoides small colony (SC) type, the agent
      of contagious bovine pleuropneumonia (CBPP), were analysed with respect to the
      polymorphism of distribution of a newly discovered insertion element, IS1296, on
      the chromosome. Analysis of 64 strains isolated from Europe, Africa and
      Australia, including four vaccine strains and the type strain PG1, revealed ten
      different IS patterns, forming two main clusters. The European strains originated
      from outbreaks of CBPP in different countries, and from various other sources
      such as semen and preputial washings from cattle, lungs from goats and buffalo,
      and milk from sheep. They showed identical IS1296 patterns, except one strain
      which had an additional IS1296 element, but the pattern belonged to the same
      cluster. This shows that the strains from Europe form a clonal lineage. The
      strains originating from different geographical parts of the African continent
      and from Australia showed four closely related IS1296 patterns which belong to a
      separate cluster. This indicates that strains from Africa and Australia form a
      clonal lineage different from that of the European strains, suggesting that the
      sporadic cases of CBPP that have re-emerged in Europe almost 15 years after the
      last declared endemic case in 1967 arose from an established reservoir within
      Europe rather than being the result of repeated importation from Africa and
      Australia. While most strains from Africa and Australia had the same IS1296
      pattern, all vaccine strains could be distinguished by an individual pattern. The
      type strain PG1 also had a particular IS1296 pattern which belongs to the cluster
      of the strains from Africa and Australia. The molecular definition of clonality
      of M. mycoides subsp. mycoides SC strains with IS1296 represents a rapid and
      reproducible method for subtyping and differentiation of vaccine strains. It
      permits at the present time the definition of two main clonal lines, one
      including the strains from the European continent and a second with strains from
      Africa and Australia.

PMID- 8574414
TI  - tRNA intergenic spacers reveal polymorphisms diagnostic for Xanthomonas
      albilineans.
AB  - A PCR-based detection system was developed for Xanthomonas albilineans, a
      pathogen of sugarcane, and other related xanthomonads, using the conserved
      sequence of two adjacent tRNA genes and the variable length and sequence of the
      spacer region between them. An appropriate region was identified as follows: tRNA
      genes with the same anticodon from a wide variety of bacteria were aligned and
      the most frequent base at each position was chosen to derive primers that would
      anneal to the gene in either orientation. Pairs of such primers were screened
      against various Xanthomonas species and members of related genera using PCR at
      low to moderate annealing stringency. A subset of these pairs of tRNA consensus
      primers gave one or more PCR products which generally displayed interspecific
      length variability. The primer pair 5'-3' tRNA(ala) and 3'-5' tRNA(ile) showed
      interspecific length polymorphisms between X. albilineans and all other
      Xanthomonas species examined. These PCR products were cloned and sequenced from
      four isolates of X. albilineans and four isolates from different pathovars of X.
      campestris, and the spacer length variation confirmed. Specific tRNA gene primers
      were derived from the tRNA gene sequences. These primers yielded a PCR product of
      a characteristic length within most Xanthomonas species and pathovars tested.
      When a primer that projected from tRNA(ala) into the 3' end of the variable
      intergenic spacer was used with a tRNA(ile)-specific primer, PCR was a very
      sensitive diagnostic test for X. albilineans-infected sugarcane and gave no
      product or only a faint product with other species of bacteria. The specificity
      of this PCR-based detection system was further enhanced by a nested PCR reaction
      that took advantage of the fact that the tRNA(ala)-tRNA(ile) region was found to
      be embedded in a 16S rRNA-23S rRNA gene spacer. By amplifying the region between
      the 16S rRNA gene and tRNA(ile) or between the tRNA(ala) and the 23S rRNA gene,
      the subsequent nested PCR product was shown to be X. albilineans-specific.

PMID- 8574416
TI  - A mother and three daughters with congenital dislocation of the hip and a
      characteristic facial appearance: a new syndrome?
AB  - We describe a mother and her three daughters who all have bilateral congenital
      dislocation of the hip. The mother has had no other medical problems and is on
      the 90th centile for height. Her three daughters resemble each other strongly
      with facial characteristics which include hypertelorism, epicanthic folds,
      puffiness around the eyes, a flat mid-face and a carp-shaped mouth. All three
      daughters are on the 3rd centile for height, with their head circumference on a
      higher centile and all had an ASD. Other features include congenital dislocation
      of one knee (one), congenital inguinal hernia (one) and vesico-ureteric reflux
      (one). They also have clinodactyly and hyperextensible finger joints, both
      features also seen in their father, whose height is on the 3rd centile and who
      had bilateral congenital inguinal herniae. Collagen studies of skin and ligament
      were normal. This family does not appear to fit with any of the recognized
      congenital dislocation syndromes and we suggest that they may represent a
      previously undescribed syndrome.

PMID- 8574415
TI  - Determination of a 17,484 bp nucleotide sequence around the 39 degrees region of
      the Bacillus subtilis chromosome and similarity analysis of the products of
      putative ORFs.
AB  - We have determined a 17,484 bp nucleotide sequence around the 39 degrees region,
      located about 480 kb downstream from the zero position of the Bacillus subtilis
      chromosome physical map. Among the 17 putative ORFs identified, orf1 and orf2
      seem to correspond to mtlA and mtlB, encoding mannitol-specific
      phosphotransferase enzyme II and mannitol-1-phosphate dehydrogenase,
      respectively. orf4 seems to be another signal peptidase I gene (sipS) of B.
      subtilis. The putative products of six ORFs were similar to known proteins in
      data banks, namely a hypothetical 29.7 kDa protein of Escherichia coli (Orf7), a
      lactam utilization protein (Orf8), the urea amidolyase of yeast (Orf12), the IcIR
      regulatory protein for aceAB of Salmonella typhimurium (Orf13), penicillin
      binding protein 2 (Orf16) and aryl-alcohol dehydrogenase (Orf17). The amino acid
      sequence of Orf3 showed 34% identity with that of LeuC of B. subtilis, though
      they seem to be functionally different. The remaining seven ORFs did not show
      similarity to any known proteins.

PMID- 8574418
TI  - A new X-linked mental retardation syndrome.
AB  - There are now more than 70 X-linked mental retardation syndromes associated with
      physical findings documented in McKusick's "Mendelian Inheritance in Man". We
      describe a boy and his maternal uncle who appear to have a previously unreported
      X-linked mental retardation syndrome, consisting of moderate mental retardation,
      coarse facial features, epilepsy and slowly progressive joint contractures.

PMID- 8574417
TI  - Three mildly retarded siblings with congenital cataracts, sensorineural deafness,
      hypogonadism, hypertrichosis and short stature: a new syndrome?
AB  - We report three male siblings with mild mental retardation, congenital cataract,
      sensorineural deafness, hypogonadism, hypertrichosis and short stature. This
      combination has not been previously reported and we suggest this is a new
      syndrome. Although X-linked recessive inheritance cannot be fully excluded, we
      favour autosomal recessive inheritance because of parental consanguinity.

PMID- 8574419
TI  - Family studies in chromosome 22q11 deletion: further demonstration of phenotypic
      heterogeneity.
AB  - We describe three unrelated, Scottish infants with the velocardiofacial/DiGeorge
      syndrome, all of whom have deletions of chromosome 22q11. Two of the infants had
      inherited the deletion from their mothers; the third infant's mother had clinical
      features although a deletion was not demonstrable in her. One infant had
      craniosynostosis associated with broad thumbs which may be a separate familial
      trait; however, at least one other 22q11 deleted individual with craniosynostosis
      is known and it is possible that craniosynostosis is a rare feature of this
      deletion syndrome. The second infant is the third reported case with isolated
      hypoparathyroidism and dysmorphic features associated with the 22q11 deletion.
      The variable clinical phenotype of these families with 22q11 deletion is
      discussed and compared with other reported families.

PMID- 8574420
TI  - Absent iris stroma, narrow body build and small facial bones: a new association
      or variant of SHORT syndrome?
AB  - We report four patients from two unrelated families with strikingly similar
      facial appearance, short stature, narrow body build and, in two of the patients,
      abnormalities of the iris stroma. The birth of an affected offspring suggests
      that this syndrome is likely to have autosomal dominant inheritance. The facial
      appearance and some of the features resemble the SHORT syndrome, the name being
      an acronym for Short stature, Hyperextensible joints, Ocular depression, Rieger
      anomaly and abnormalities of the Teeth. The relationship of the syndrome to the
      SHORT syndrome is discussed.

PMID- 8574422
TI  - Nevo syndrome.
AB  - We describe a male patient born to consanguineous parents with a syndrome of tall
      stature at birth, hypotonia, wrist drop and long spindle shaped fingers. The
      clinical features are identical to those previously described in three cases from
      a single family by Nevo et al. (1974: J Med Genet 11: 158-165). Autosomal
      recessive inheritance is supported by consanguinity in our case. Follow-up at age
      3 years demonstrated significant improvement of hypotonia and motor function, and
      normal cognitive ability.

PMID- 8574421
TI  - Morning Glory fundus anomaly, coloboma of the optic nerve, porencephaly and
      hydronephrosis in a newborn infant: MCPH entity.
AB  - The association of Morning Glory anomaly with intracranial pathology has been
      rarely described and seems to be a distinct one. A 41-week full-term infant
      presenting with Morning Glory anomaly and multiple major and minor anomalies with
      a normal karyotype is described. Right Parieto-occipital porencephaly with mild
      hydrocephaly of lateral ventricle, right brain atrophy and enlarged thalami were
      observed by repeated ultrasound, computed tomography and magnetic resonance
      imaging examinations. Fundoscopy, visual evoked response and electroretinography
      revealed bilateral colobomas of the optic nerve, bilateral Morning Glory optic
      disc anomaly, severe exotropia and medial recti paralysis. Non-obstructive, non
      refluxing left hydronephrosis and left hydroureter were diagnosed by renal
      investigations. To the best of our knowledge the association of the described
      malformations has never been previously reported. The clinical and nosological
      significance of this new entity is discussed.

PMID- 8574423
TI  - A four generation hidrotic ectodermal dysplasia family: an allelic variant of
      Clouston syndrome?
AB  - A four generation Scottish family with hidrotic ectodermal dysplasia affecting
      predominantly teeth, skin and hair is described. Hypo- or oligodontia of the
      secondary dentition by late adolescence was characteristic and two individuals
      had multiple natal teeth. Flexural acanthosis nigricans during childhood and
      early adolescence is a feature in some of the women. All affected individuals
      produced sweat, but heat tolerance was variable. Hypoplasia of the pilosebaceous
      units was found on light microscopy in one subject. Scalp hair was thin and slow
      growing (but adult females described much improved quality during pregnancy) and
      body hair was scanty. Scanning electron microscopy of hair samples showed
      abnormal cuticular appearances consistent with a primary defect affecting keratin
      structure. The nails were normal. Relative macrocephaly due to hyperostosis of
      the cranial vault was variably present. Short stature (5-10th centile) present in
      some cases is possibly a separate familial trait. The family demonstrates
      overlapping features with Clouston syndrome. In Clouston syndrome, however,
      alopecia can be severe, palmarplantar hyperkeratosis is usually present, and
      hypo/oligodontia is not a prominent feature.

PMID- 8574424
TI  - Sporadic trichodental dysplasia with microcephaly and mental retardation.
AB  - Trichodental syndrome is a rare autosomal dominant ectodermal dysplasia. Hair and
      dental anomalies have been found in different combinations in most affected
      persons in three families. The features of trichodental syndrome were observed in
      a young female in which sparse, fine, lustreless and slow growing hairs were
      associated with bigeminismus of inferior lateral incisors. Ultrastructural hair
      analysis showed consistent variation in contour of the shaft and reduced to
      absent cuticular scale. Distinguishing features in this patient were microcephaly
      and mild mental retardation.

PMID- 8574425
TI  - Oculoauriculofrontonasal syndrome: report of another case and review of
      differential diagnosis.
AB  - We report a male with features of frontonasal dysplasia, but also with ocular and
      auricular defects. This child most likely has oculoauriculofrontonasal syndrome,
      an autosomal recessive syndrome first described in 1981. We also review the
      literature on this syndrome, and discuss differential diagnosis.

PMID- 8574426
TI  - Multiple lateral meningoceles, distinctive facies and skeletal anomalies: a new
      case of Lehman syndrome.
AB  - We describe a 19-year-old boy who presented with facial dysmorphism, multiple
      lateral meningoceles, skeletal abnormalities and normal intelligence.
      Neurofibromatosis and Marfan syndrome were excluded. Electron microscopy of the
      skin showed non-specific abnormalities suggesting a connective tissue disorder.
      The features of this boy closely resemble those in a mother and daughter with
      Lehman syndrome.

PMID- 8574427
TI  - Fryns syndrome: two further cases without lateral diaphragmatic defects.
AB  - We report on two unrelated infants with Fryns syndrome but without lateral
      diaphragmatic defects. In case 1, a female stillborn, pertinent findings included
      a coarse facies, cleft palate, short neck with a broad pterygium, heart defect,
      lung hypoplasia, omphalocele, urogenital malformations, anal atresia, and distal
      digital hypoplasia. Case 2 showed a coarse facies with cleft lip and palate, para
      oesophageal hernia with herniation of the stomach into the thoracic cavity,
      malrotation of the intestine, hydronephrosis, and anal atresia. At age 14 months
      she was developmentally severely retarded. These observations represent the 11th
      and 12th reports of probable Fryns syndrome without lateral diaphragmatic defect.

PMID- 8574428
TI  - Transverse limb deficiency, facial clefting and hypoxic renal damage: an
      association with treatment of maternal hypertension?
AB  - Transverse limb defects are reported in a fetus and an infant born to mothers on
      treatment for hypertension. One pregnancy resulted in an intrauterine death at 20
      weeks, and in addition to the limb defects, there was bilateral cleft lip and
      palate and renal hypoxic damage. It is proposed that the drugs caused maternal
      hypotension which led to reduced uteroplacental blood flow, fetal hypotension and
      hypoxia and that the anomalies seen in the two babies are a consequence of these
      events.

PMID- 8574429
TI  - Double trisomies.

PMID- 8574430
TI  - Interleukin-4 and soluble CD23 serum levels in asthmatic atopic children.
AB  - IL-4 is an essential mediator of IgE synthesis; it also upregulates the
      expression of the low affinity receptor for IgE (CD23) and its release in soluble
      form (sCD23). The involvement of IL-4 and sCD23 on the IgE synthesis control has
      been observed in experimental studies. IL-4 and sCD23 serum levels in asthmatic
      atopic children were determined in order to investigate a possible correlation
      between these factors and IgE levels. IL-4, total sCD23 and Dermatophagoides
      pteronyssinus specific IgE were determined in the serum of 19 asthmatic atopic
      children (aged 7 to 14) and in 13 age-matched controls. Since sCD23 may present
      an age-dependent variation, sCD23 and IL-4 serum levels were evaluated in 20
      "wheezy babies." IL-4 serum levels were significantly higher in patients as
      compared to controls, whereas there was no significant difference between them
      concerning sCD23 levels. sCD23 levels were, however, significantly higher among
      "wheezy babies" as compared to atopic and nonatopic children. There was no
      correlation between IL-4 and sCD23 serum levels, nor between any of these factors
      and IgE levels in all groups. In conclusion, the enhanced IL-4 levels suggest
      that atopic patients have a preferential activation of Th2 subset. CD23
      expression is markedly influenced by age.

PMID- 8574431
TI  - Interleukin 2-dependent immunoregulatory function in hemodialysis patients with
      chronic hepatitis C.
AB  - To investigate the state of activation of T lymphocytes in hemodialysis patients
      with chronic hepatitis C, serum levels of soluble interleukin-2 receptors (sIL
      2R), interleukin-2 (IL-2) and expression of interleukin-2 receptors (IL-2R) on
      peripheral T lymphocytes were measured in 30 hemodialysis patients with chronic
      hepatitis C, 14 hemodialysis patients without hepatitis, 30 patients with chronic
      hepatitis C and 41 normal subjects. A significant increase in sIL-2R levels was
      noted in all patients with chronic hepatitis compared to normal controls. This
      increase was even more significant in hemodialysis patients, while a less
      significant increase was also found in hemodialysis patients without hepatitis C
      viral infection. Expression of IL-2R on T lymphocytes was increased only in
      hemodialysis patients with chronic hepatitis. All patients had low levels of
      serum IL-2. These findings show that a T-cell activation involving the IL-2
      system is present in chronic hepatitis C and that this activation is more
      prominent in hemodialysis patients, probably due to additional extrahepatic
      factors.

PMID- 8574432
TI  - Effect of hyposensitization for tree pollinosis on associated apple allergy.
AB  - Twenty patients suffering from birch pollen allergy received two or three courses
      of immunotherapy in successive years. In 9 patients, the fruit allergy improved;
      4 patients reported no improvement. In 3 patients, the fruit allergy developed
      after beginning the immunotherapy. At the end of the 3 years, 16 of these
      patients were allergic to fruit, 13 of them to apple. After each preseasonal
      course of immunotherapy with tree pollen extract, a temporal and parallel
      increase in the titers of IgE antibodies to birch pollen allergens and apple
      allergens were observed. In contrast, only the titers of birch pollen allergen
      specific IgG and IgG4 increased, whereas apple allergen specific IgG and IgG4 did
      not, or only very slightly. In Western blot studies, IgG4 antibodies bound to
      more components of apple extract than birch pollen extract. On the average, IgG4
      antibodies recognize more components of apple and birch pollen extracts than do
      IgE antibodies. In histamine release studies, the sensitivity of washed
      leukocytes to birch pollen extract decreased significantly during the observation
      time. However, the difference between apple extract-induced histamine release
      before and after immunotherapy was not significant. None of the immunological
      parameters investigated here correlate well with severity or prognosis of the
      fruit (apple) allergy. The clinical improvement of pollinosis was associated with
      a rise in birch pollen specific IgG4 antibody titers and a decrease of allergen
      induced histamine liberation. Beside improvement of the fruit allergy in 56% of
      the cases, the courses of apple specific IgE and IgG4 antibody titers seem to
      indicate a slight sensitization against apple allergens.

PMID- 8574434
TI  - The value of C1 esterase inhibitor in patients with aspirin-sensitive urticaria.
AB  - The aim of the study was to evaluate the concentration and activity of C1
      esterase inhibitor (C1 INH) in patients with aspirin-sensitive urticaria. C1 INH
      deficiency is the basis of hereditary angioneurotic edema. The study was
      performed on 32 subjects with aspirin-sensitive urticaria. The value of C1 INH in
      examined patients was the same as in the control group. There seems to be no
      coexistence of aspirin-sensitive urticaria and C1 esterase inhibitor deficiency.

PMID- 8574433
TI  - Cutaneous immediate and late phase reactions to schistosomin in schistosomiasis
      patients.
AB  - Cutaneous immediate and late phase reactions (LPR) to schistosomin were studied
      in 29 patients with schistosomiasis mansoni. In 12 of these patients, the
      determination of total and specific serum IgE by immunoenzymatic method against
      schistosome antigen was carried out using serum samples obtained on the same day
      as the cutaneous tests. Skin biopsies were taken from 4 typical LPRs. Immediate
      reactions occurred in all except one and LPRs in 12 (41.3%). Patients with
      positive cutaneous reactions had highe levels of specific serum IgE against
      schistosome antigen. Histopathological studies showed a moderate exudate
      consisting mainly of neutrophils (60%) and eosinophils (40%). LPRs in
      schistosomiasis have the same characteristics reported in the medical literature
      in relation to time of appearance, morphology and histopathology. The
      immunopathogenic role played by LPRs in the patients remains to be clarified.

PMID- 8574435
TI  - Hypersensitivity reactions to drugs: correlation between clinical probability
      score and laboratory diagnostic procedures.
AB  - The in vitro diagnosis of allergic drug reactions have not made significant
      progress in recent years. Specific stimulation of lymphocytes from allergic
      patients represents an approach to demonstrating sensitization to the implicated
      drug. So far, skin tests and RAST can only be applied to a limited number of
      situations. The purpose of this study was to standardize the clinical criteria in
      order to establish a clinical probability score for each drug. Independently, the
      various laboratory procedures mentioned were compared with the established
      clinical probability score for each drug. The results showed that, for the few
      common drugs studied, the correlation between the clinical probability score and
      the results of the in vitro lymphocyte transformation test was significant. A
      significant correlation between the clinical probability score and the skin tests
      was only shown for penicillin and its derivatives.

PMID- 8574436
TI  - Passive cutaneous anaphylaxis in diabetic rats.
AB  - The effect of diabetic condition on heterologous passive cutaneous anaphylaxis
      (PCA) reaction was studied. In alloxan diabetic rats, PCA reaction was inhibited
      by 68.2% of control values. The skin hyposensitivity in diabetic rats could not
      be attributed to a lower quantity of skin mast cells; it is suggested that
      alterations in the endothelial cells of the microcirculatory blood vessels
      decrease permeability to biologically active mast cell factors.

PMID- 8574437
TI  - Action of nedocromil sodium in exercise-induced asthma in adolescents.
AB  - In view of the high incidence of exercise-induced asthma (EIA) in asthmatic
      adolescents and adults, the aim of the present study was to examine the
      preventive effect of nedocromil sodium administered prior to an exercise
      provocation test. The study involved 30 adolescents with EIA, aged between 14 and
      19 years, who attended gymnastics classes at the Children's Hospital and Aerobics
      School. Baseline spirometry, six-minute treadmill running and spirometry for 7-15
      minutes post-exercise were performed. During the same week and under identical
      temperature and humidity conditions, the same test was carried out with 4 mg
      nedocromil sodium (two inhalations) administered 30 minutes before exercise.
      Original post-exercise FEV1 values were compared with the findings after
      administration of nedocromil sodium. Seventeen subjects (56%) were totally
      protected (< 5% decrease in FEV1) and 13 subjects (44%) were partially protected
      (< 10% decrease in FEV1). EIA persisted in the fifteen subjects who received
      placebo pretreatment. Nedocromil sodium, administered 30 minutes prior to
      exercise, was effective, providing an opportunity to enhance the quality of life
      of the asthmatic patient troubled by exercise-induced symptoms.

PMID- 8574438
TI  - Reliability of histamine release test in dust mite allergy: influence of the
      degree of sensitization.
AB  - The histamine release test has been proven to be a very useful method for in
      vitro diagnosis of IgE-mediated allergy to inhalant and food allergens, as well
      as for the immunotherapy follow-up of the allergic patient. The aim of the
      present study was to assess the influence of the degree of sensitization in
      allergic patients sensitive to Dermatophagoides pteronyssinus on their dose
      response curves in histamine release tests. To achieve this aim, we studied 109
      D. pteronyssinus allergic patients and 25 healthy control subjects.
      Intracutaneous skin test, D. pteronyssinus-specific and total IgE quantitations,
      and histamine release tests were carried out in all the patients. In the case of
      the histamine release test, five D. pteronyssinus extract concentrations were
      used (2822.5, 282.25, 28.22, 2.82 and 0.28 UBE/ml), and two patterns of histamine
      release in sensitive patients were found: one with maximal histamine release at
      the highest antigen concentration (group I) and the other with maximal release
      attained at lower concentrations (group II). A sensitization score was designed,
      after the results from specific IgE and intracutaneous skin tests. There were
      significant differences (p < 0.05) in antigen-specific and total IgE levels, and
      in papule diameters and sensitization scores, between the control group and
      groups I and II. Both groups showed significantly higher (p < 0.05) histamine
      releases than the control group in response to anti-IgE antibodies. When
      stimulating the cells with anti-IgE antibodies, histamine release in group II was
      higher than in group I, although this difference was not significant. Finally,
      the best correlation between sensitization score and antigen-specific histamine
      release was found at the 2.82 UBE/ml concentration (r = 0.84, p < 0.001).

PMID- 8574439
TI  - Successful desensitization of a child with desferrioxamine hypersensitivity.
AB  - Desferrioxamine is produced by a type of actinomycetes. It reacts with trivalent
      iron ions and forms a hydrosoluble complex called ferrioxamine B. This complex is
      able to remove iron from ferrous protein, but not from hemoglobin. This feature
      permits its use for the treatment of chronic iron accumulation such as that which
      occurs in thalassemia. Only two cases of successful desensitization to
      desferrioxamine hypersensitivity have been previously described. This paper
      describes a case of desensitization in a six-year-old girl with desferrioxamine
      hypersensitivity. She suffered from Cooley's disease and had received blood
      transfusions since the age of three months. From the age of four years, the
      patient was treated with desferrioxamine, which was interrupted after the
      occurrence of urticaria-angioedema. Skin and patch tests an in vitro lymphocyte
      transformation test were negative, indicating a pseudoallergic reaction. The
      desensitization treatment lasted twenty-one days and, afterwards, the patient was
      able to tolerate desferrioxamine therapy at the dose previously administered (400
      mg/day, subcutaneously).

PMID- 8574440
TI  - Outgroup heteroduplex analysis using temperature gradient gel electrophoresis:
      high resolution, large scale, screening of DNA variation in the mitochondrial
      control region.
AB  - The ability of DNA screening techniques such as Temperature Gradient Gel
      Electrophoresis (TGGE) and Heteroduplex Analysis to provide resolution
      approaching that provided by DNA sequencing for a fraction of the time, effort
      and expense point to them as the logical successor to allozyme electrophoresis
      for population genetics. Here we present a novel alternative to the standard
      TGGE/Heteroduplex Analysis protocol - Outgroup Heteroduplex Analysis (OHA). We
      assess this technique's sensitivity in comparison to previous screening
      approaches using a known hierarchy of sequence differences. Our data show that
      Outgroup Heteroduplex Analysis has greatly increased sensitivity for screening
      DNA variants from that of TGGE used alone and is easily applicable to large
      numbers of samples. Using this technique we can consistently detect differences
      of as small as one base change in a 433-base-pair fragment of Control Region
      mitochondrial DNA from Melomys cervinipes (an Australian rodent). The approach
      should easily be extendable to nuclear loci and is not necessarily dependent on
      the use of a denaturing gradient. When combined with a targeted sequencing
      effort, OHA provides a sensitive and simple means of obtaining allele/haplotype
      frequencies and their phylogenies for population and phylogeographic studies in
      molecular ecology.

PMID- 8574441
TI  - PCR amplification of intergenic spacers in the ribosomal DNA of Drosophila
      melanogaster reveals high levels of turnover in length and copy-number of spacers
      in geographically separated populations.
AB  - A recently described PCR-based method for the analysis of intergenic spacer (IGS)
      length variation in the ribosomal (r) DNA of Drosophila melanogaster was used to
      analyse the distribution of IGS length variants in the rDNA of a number of
      recently collected D. melanogaster populations. One group of populations, from
      Europe and North Africa, was shown to have low intrapopulation IGS length
      variation following maintenance of massed populations in the laboratory for an
      extended period. However, a greater degree of IGS profile variability was
      detected at a number of levels in the majority of laboratory-maintained isofemale
      lines from two of these populations plus a second group of populations which were
      collected more recently from the eastern coast of Australia; all of which were
      immediately divided into isofemale lines following collection. Interestingly, PCR
      analysis of pooled DNA extracts from 30 individuals of either sex showed almost
      identical PCR profiles from each of the Australian populations. These preliminary
      results are discussed with regard to the possible combinations of forces (natural
      selection, neutral drift and genomic molecular drive) on the patterns of IGS
      length variation.

PMID- 8574442
TI  - Mitochondrial DNA variation, population structure, and evolution of mountain
      sheep in the south-western United States and Mexico.
AB  - In the south-western United States and Mexico, mountain sheep were found to have
      low levels of mtDNA sequence divergence among haplotypes and low overall
      nucleotide diversity. Potential causes for this low diversity are discussed.
      Significant differences in mtDNA haplotype distributions over short distances and
      high values of NST on a local scale appear to be a result of the tendency of
      female mountain sheep to disperse less frequently and over shorter distances than
      males. A lack of concordance between mtDNA haplotype distributions and assumed
      subspecies boundaries suggest that some taxonomic labels need to be revised.

PMID- 8574443
TI  - Mitochondrial DNA products among RAPD profiles are frequent and strongly
      differentiated between races of Douglas-fir.
AB  - Racial differentiation and genetic variability were studied between and within
      the coastal, north interior, and south interior races of Douglas-fir using RAPD
      and allozyme markers. Nearly half of all RAPD bands scored (13: 45%) were found
      to be amplified from mitochondrial DNA. They exhibited maternal inheritance among
      hybrids and backcrosses between the races, and were much more highly
      differentiated (GST = 0.62 for haplotype frequencies) than were allozymes (GST =
      0.26). No evidence of hybridization or introgression was detected where the
      coastal and interior races come into proximity in central Oregon.

PMID- 8574444
TI  - Molecular structure of the Frankia spp. nifD-K intergenic spacer and design of
      Frankia genus compatible primer.
AB  - The nifD-K intergenic spacer (IGS) of ArI3 and ACoN24d were found to have a
      length 265 and 199 nucleotides, respectively. They are markedly less conserved
      than the two neighbouring genes and have, in some instances, a repeated structure
      reminiscent of an insertion event. The repeated sequence and the IGSs have no
      detectable homology with sequences in DNA databanks. The IGS has a stem-loop
      structure with a low folding energy, lower than that between nifH and nifD. No
      convincing alignment of IGS sequences could be obtained among Frankia strains.
      Only between ACoN24d and ArI3, which belong to the same genomic species, was the
      alignment good enough to permit detection of a doubly repeated structure. No
      promoter could be detected in the IGSs. The putative nifK open reading frame
      (ORF) in Frankia strain ArI3 has a length of 1587 nucleotides, starting with a
      GTG codon, preceded by a ribosome binding site of a structure similar to that of
      nifH (GGAGGN7). The codon usage was similar to that of previously sequenced
      Frankia genes with a strong bias toward G- and C-ending codons except in the case
      of glycine where GGT is frequent. Alignment of the three Frankia nifK sequences
      (EUN1f; ArI3 and ACoN24d) with those of other nitrogen-fixing bacteria permitted
      detection of a sequence conserved among the three Frankia strains but absent in
      the other sequences. A primer targeted to that region in combination with FGPD807
      85 amplified the nifD-KIGS sequences of all Frankia strains (except the non
      nitrogen-fixing Frankia strains CN3 and AgB1-9) and yet failed to amplify DNA of
      all other nitrogen-fixing bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574445
TI  - Resolving genetic relationships with microsatellite markers: a parentage testing
      system for the swallow Hirundo rustica.
AB  - Eight polymorphic microsatellite markers from the swallow were isolated and
      characterized. Extraordinary variability was revealed at the HrU6 locus with 45
      different alleles scored among 46 unrelated individuals. The probability that the
      same genotype combination would occur in two random and unrelated individuals at
      six selected loci was as low as 1.3 x 10(-8) and the combined exclusion
      probability was 0.9996. Stable Mendelian inheritance was observed in about 1000
      meioses. No significant linkage was revealed and for almost all combinations of
      marker-pairs, linkage closer than 5 cM could be excluded. At two loci, null
      (nonamplifying) alleles were encountered. Thirteen (30%) extra-pair offspring
      were identified in 5 (56%) broods when applying the marker set on a nearly
      complete swallow colony. We were able to identify a single male from the other
      families in the colony as the most likely father for nine of the 13 extra-pair
      offspring.

PMID- 8574446
TI  - Use of the PCR and fluorescent probes to recover SSU rRNA gene sequences from
      single cells of the ciliate protozoon Spathidium.
AB  - A two-stage heminested PCR approach was developed to amplify small subunit (SSU)
      rDNA sequences, via two overlapping fragments, from single cells of microbial
      eucaryotes. The method was evaluated using the ciliate protozoon Spathidium when
      PCR products were obtained from nine of 10 cells tested. Southern blotting
      demonstrated that all fragments contained the same sequence in a region of SSU
      rDNA which is normally highly variable between species. A fluorescent
      oligonucleotide probe was used to demonstrate that this sequence also occurred in
      fixed cells of Spathidium. Fixatives containing mercuric salts preserved cell
      shape and allowed probe binding with little background autofluorescence. The
      Spathidium sequence is closely related to that from the haptorid Homalozoon
      vermiculare.

PMID- 8574447
TI  - Multiple paternity in the red-eyed treefrog Agalychnis callidryas (Cope).
AB  - DNA fingerprinting of tadpoles from two different 'one female-two male' matings
      of the red-eyed treefrog, Agalychnis callidryas, revealed multiple paternity of
      offspring. Offspring were assigned paternity based on bands shared with the
      putative father, but not shared between putative fathers or with the mother.
      Paternity was split approximately 44/56% and 36/64% in two matings. These results
      do not support a hypothesis of sperm priority in access to unfertilized eggs by
      primary males. Multiple paternity may be commonplace in species of anurans with
      matings by multiple males.

PMID- 8574448
TI  - PCR-based identification of wheat genomes.
AB  - We describe a PCR system that distinguishes the A, B and D genomes in wheat DNA
      extracts. PCRs were directed at the 'non-transcribed spacer' regions of the rDNA
      loci. The spacers within the D genome locus have a 71-bp insertion that is absent
      from the corresponding A and B loci. PCR product sizes therefore enable D- and D+
      genomes to be distinguished. The A and B genomes can be differentiated by PCR
      with an internal primer which does not anneal to A genome sequences. This work is
      relevant to the ancient ecology of wheat, as it is often difficult to determine
      ploidy level from morphological examination of archaeobotanical remains.

PMID- 8574449
TI  - The molecular basis and evolutionary history of a microsatellite null allele in
      bears.

PMID- 8574450
TI  - Highly variable microsatellites in isolated colonies of the rock-wallaby
      (Petrogale assimilis).

PMID- 8574451
TI  - Primers for amplification and determination of mitochondrial control-region
      sequences in oscine passerines.

PMID- 8574452
TI  - Clinical importance of determining the presence of myocardial viability.

PMID- 8574453
TI  - Assessment of myocardial viability by dobutamine echocardiography.

PMID- 8574454
TI  - Clinical aspects of myocardial stunning.

PMID- 8574455
TI  - Assessment of myocardial viability by ultrasonic tissue characterization.
AB  - In conclusion, myocardial tissue characterization with quantitative ultrasonic
      indices descriptive of the physical state of the tissue is a promising approach
      to complement conventional echocardiography in the evaluation of patients with
      coronary artery disease. In particular, differentiation among hibernating,
      stunned and scarred myocardium may be possible on the basis of the experience
      accumulated thus far.

PMID- 8574456
TI  - Perfusion imaging with contract echocardiography: assessment of the no-reflow
      phenomenon.

PMID- 8574457
TI  - Clinical assessment of regional function: strengths and limitations.

PMID- 8574458
TI  - NIDDM as unfavorable factor to the postinfarctual ventricular function in the
      elderly: echocardiography study.
AB  - BACKGROUND: Aging and diabetes mellitus have been recognized as strong predictors
      of heart failure in patients with acute myocardial infarction. The aim of this
      study was to assess, by echocardiography, the influence of aging and non-insulin
      dependent diabetes mellitus on the changes of left ventricular parietal kinesis
      in patients with acute myocardial infarction over the 6 months after
      hospitalization. METHODS: The study population consisted of 82 patients (42 male,
      40 female) aged 70 years, consecutively admitted to coronary care unit with acute
      myocardial infarction from January 1991 to May 1993. They were divided into two
      groups: group 1 comprised 36 patients with non-insulin-dependent diabetes
      mellitus, aged 78.8 +/- 6.02 years, 17 men and 19 women; group 2 comprised 46
      patients without diabetes aged 78.7 +/- 6.9 years, 25 men and 21 women.
      Echocardiography was performed at admission to the unit (T0), at discharge (T1),
      and after 6 months of follow-up (T2). The echocardiographic wall motion score
      index was calculated by considering the number of akinetic and dyskinetic left
      ventricular wall segments. Fatal and non-fatal incidents of heart failure were
      also considered and a multivariate analysis was applied to identify the clinical
      and instrumental parameters that were independent predictors of wall motion score
      index changes and heart failure events. RESULTS: At T1 the two groups were
      comparable in localization of acute myocardial infarction, previous myocardial
      infarction, creatinine kinase serum peak, ECG score and wall motion score index.
      A statistically significant reduction in akinesia (P < 0.001) was observed in
      group 2 at T1 and T2, but was not seen in group 1. At T2 the difference in wall
      motion score index between the groups became significant (P < 0.05). The
      occurrence of heart failure was significantly higher in group 1 than in group 2
      either during hospitalization (P < 0.03) or during follow-up (P < 0.004). The
      multivariate analysis identified non-insulin-dependent diabetes mellitus as an
      independent predictor of lacking recovery in LV kinesis (P < 0.01) and of heart
      failure development (P < 0.001). CONCLUSION: In elderly patients with non-insulin
      dependent diabetes mellitus lack of recovery in wall motion score index after
      acute myocardial infarction seems to be an important factor, with a higher heart
      failure prevalence adversely affecting the in-hospital and long-term outcome. Non
      insulin-dependent diabetes mellitus appears to be an important factor related to
      this unfavorable outcome.

PMID- 8574459
TI  - Coronary flow and left ventricular diastolic function in aortic regurgitation.
AB  - BACKGROUND: An abnormal coronary perfusion pressure is probably the major
      determinant of altered myocardial perfusion in aortic regurgitation; ventricular
      hypertrophy and diastolic function may also be involved. This study was
      undertaken to investigate the respective roles of these two variables. METHODS:
      Using multiplane transesophageal echocardiography, we evaluated the coronary
      Doppler flow velocity in the proximal left anterior descending coronary artery in
      15 patients with aortic regurgitation before and immediately after valve
      replacement. The ratios of diastolic:systolic velocity integral and early:late
      diastolic velocity integral were correlated against coronary perfusion pressure,
      pulmonary wedge pressure and Doppler echocardiographic indices of left
      ventricular diastolic function. Patients were compared with 10 subjects without
      valvular diseases. RESULTS: Aortic regurgitation was associated with a reduction
      of the coronary diastolic:systolic velocity integral ratio and increment in the
      early:late diastolic velocity integral ratio. The latter correlated positively
      with early:late diastolic ratio of mitral flow velocity, pulmonary wedge pressure
      and left ventricular mass index. Soon after valve replacement, a decrease in
      pulmonary wedge pressure and a rise in coronary perfusion pressure were seen.
      Both the echo-Doppler parameters related to diastolic function and the
      systodiastolic distribution of coronary flow returned to normal. This indicates
      that diastolic dysfunction rather than left ventricular mass may be related to a
      disordered myocardial perfusion. CONCLUSIONS: In aortic regurgitation, a
      relationship exists between diastolic ventricular function and coronary flow
      phasic distribution. Valve replacement improves the former and normalizes the
      latter. Echo-Doppler parameters of diastolic dysfunction identify patients with
      worse coronary perfusion and might represent an additional criterion in the
      preoperative evaluation of patients with aortic regurgitation.

PMID- 8574460
TI  - Can the risk for acute cardiac events in acute coronary syndrome be indicated by
      platelet membrane activation marker P-selectin?
AB  - BACKGROUND: P-selectin, an adhesion molecule of the selectin family, is expressed
      on the surface of activated thrombocytes by thrombin. The aim of the present
      study was to assess the predictive value of P-selectin (estimated by flow
      cytometric assay) for acute cardiac events in acute coronary syndrome. METHODS:
      The study consisted of 48 patients with acute coronary syndrome and 30 healthy
      control subjects. After immediate fixation with 1% paraformaldehyde, 50
      microliters of this aliquot was incubated with phycoerythrin-CD62-related
      antigen, and then measured by flow cytometry. The short-term clinical course of
      the patients was compared with their P-selectin values. RESULTS: The average P
      selectin values in the 30 healthy volunteers was 0.11 +/- 0.20% (range, 0.0
      0.5%). Significant differences were observed between acute cardiac events in
      patients with unstable angina and high P-selectin values and those with normal P
      selectin values (chi 2 = 4.3; P < 0.05). Moreover, the angina patients who
      experienced acute cardiac events had significantly elevated P-selectin values
      (2.1 +/- 2.3%) compared with patients who did not experience acute cardiac events
      (0.3 +/- 0.4%, P < 0.05). The P-selectin values were elevated in seven out of 24
      patients who suffered acute myocardial infarction. Seven of the 14 patients with
      acute coronary syndromes and high P-selectin values required urgent percutaneous
      transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting
      (CABG), or both, otherwise they developed extension of the infarction. However,
      only five of the 34 patients with normal P-selectin values required urgent PTCA
      or CABG. Significant differences were observed in acute cardiac events between
      the high P-selectin and normal P-selectin groups (chi 2 = 4.8, P < 0.05).
      CONCLUSION: High P-selectin values indicate activation of platelets and the risk
      of acute cardiac events in patients with acute coronary syndrome.

PMID- 8574461
TI  - A closed-chest porcine model of coronary dissection and thrombosis.
AB  - BACKGROUND: Coronary dissection and thrombosis are important as
      pathophysiological mechanisms in acute coronary syndromes and as consequences of
      various interventional procedures. The present study was designed to develop and
      characterize a simple percutaneous method to produce coronary dissection and
      thrombosis in the pig. METHODS: The porous balloon (Wolinski type) was slightly
      oversized (balloon-to-artery ratio, 1.21 +/- 0.08) and placed in the left
      anterior descending artery in 12 domestic pigs using standard percutaneous
      techniques. The balloon was inflated using a pressure-activated syringe at 5 atm
      to deliver 1 ml of either saline or a small amount of bovine thrombin (500 units)
      in saline. The balloon was withdrawn, serial angiograms recorded, and ECG and
      aortic pressure were monitored throughout. At coronary occlusion or at 30 min,
      the hearts were removed and fixed for histological analysis. RESULTS: Seven pigs
      received thrombin and five received saline. On microscopic examination the
      internal elastic lamina was disrupted in all arteries in both groups. Subintimal
      and medial dissection was noted in 80% of arterial cross sections in the saline
      group, and 86% in the thrombin group. Partial occlusion of the coronary artery
      with thrombus was seen in 20% of samples in the saline group and in 43% of the
      thrombin group. Thrombus with complete occlusion of the coronary artery was
      observed in 86% of thrombin-treated vessels but in none of the arteries that
      received saline. Complete occlusion was observed at 28 +/- 9 min by angiography.
      CONCLUSIONS: Percutaneous delivery of a small amount of thrombin through a
      slightly oversized porous balloon catheter produces coronary dissection and
      thrombosis in a more reproducible and timely fashion than previously described
      methods. This model may be useful for testing interventional and pharmacologic
      treatment strategies.

PMID- 8574462
TI  - A coronary porcine organ culture system for studies of postangioplasty cell
      proliferation.
AB  - BACKGROUND: Restenosis after angioplasty is generally considered to be caused
      mainly by an increased proliferation of smooth muscle cells, but recently this
      theory has been questioned. METHODS: Fresh hearts of 25 pigs were obtained and
      the left anterior descending coronary arteries carefully prepared, cut into
      segments and treated with a 3 mm standard balloon catheter for 60 s with 3, 6, 9
      and 12 bar. Immediately after angioplasty the specimens were cultured in a
      mixture of WM/F-12, supplemented with 15% fetal calf serum. RESULTS: After
      staining with a modified Verhoeff-van Gieson technique, intimal wall thickening
      was analysed with a computerized morphometric system. After 14 days in culture,
      angioplasty with 6, 9 and 12 bar resulted in a significant (P < 0.05) increase of
      neointimal thickening. After 21 days, a significant increase of neointimal
      thickening was seen after ballooning with 3, 9 or 12 bar (P < 0.05). After 28
      days angioplasty with 3 or 6 bar showed a dose-dependent increase of neointima,
      which was not further increased after ballooning with 9 or 12 bar. Significance
      was reached after ballooning with 6, 9 and 12 bar (P < 0.05). Smooth muscle cells
      were identified with a monoclonal antibody against smooth muscle alpha-actin.
      Endothelial cells were identified using an anti-human von Willebrand factor. To
      determine the number of cells undergoing DNA synthesis, bromodeoxyuridine, a
      thymidine analogue, was added to the culture media 18 h before fixation. It was
      detected with a monoclonal antibody, with a biotinylated horse-anti-mouse
      antibody as secondary antibody. After 4 and 7 days in culture bromodeoxyuridine
      positive cells were observed, indicating an early proliferative response after
      angioplasty. CONCLUSIONS: The coronary organ culture model offers opportunities
      for investigations of complex cellular events that are considered important in
      the development of restenosis. The data reported emphasize the importance of an
      early proliferative response of smooth muscle cells after coronary angioplasty,
      resulting in a significant neointimal thickening.

PMID- 8574463
TI  - Heart rate increase and maximal heart rate during exercise as predictors of
      cardiovascular mortality: a 16-year follow-up study of 1960 healthy men.
AB  - BACKGROUND: Resting heart rate is directly associated and maximal exercise
      induced heart rate inversely associated with cardiovascular mortality, and
      therefore their difference might contain prognostic information from both
      variables. The comparative long-term prognostic values of maximal exercise
      induced heart rate and of the difference between it and resting heart rate were
      studied in apparently healthy middle-aged men. METHODS: Resting heart rate and
      maximal exercise-induced heart rate were measured, and their difference
      calculated, in 1960 apparently healthy men aged 40-59 years, and mortality was
      recorded over a period of 16 years. Conventional coronary risk factors were
      assessed at baseline. RESULTS: Both the difference between the two heart rates
      and the maximal exercise-induced heart rate were strongly, independently and
      inversely associated with cardiovascular mortality after adjustment for age,
      smoking, systolic blood pressure, lung function, glucose tolerance, serum
      cholesterol level, serum triglycerides level, physical fitness and exercise ECG
      findings. The adjusted relative risk of cardiovascular death in heart-rate
      difference quartiles 3 and 4 compared with that in quartile 1 (the lowest heart
      rate difference quartile) was 0.54 (95% confidence interval 0.33-0.86; P =
      0.009). The corresponding value for maximal exercise-induced heart rate was 0.56
      (95% confidence interval 0.34-0.89; P = 0.018). Within the lowest heart-rate
      difference quartile, but not within the lowest maximal exercise-induced heart
      rate quartile, a further, strong, negative gradient in cardiovascular mortality
      was observed. In the high working capacity range, low heart-rate difference but
      not low maximal exercise-induced heart rate predicted very high cardiovascular
      disease mortality. Heart-rate difference and maximal exercise-induced heart rate
      were also inversely associated with non-cardiovascular disease mortality.
      CONCLUSIONS: Both heart-rate difference and maximal exercise-induced heart rate
      were strong, graded, long-term predictors of cardiovascular mortality among
      apparently healthy middle-aged men, independent of age, physical fitness and
      conventional coronary risk factors. However, low heart-rate difference was a
      better predictor than low maximal exercise-induced heart rate for recognizing
      individuals who were at particularly high risk of dying prematurely from
      cardiovascular diseases.

PMID- 8574464
TI  - Bibliography of the current world literature.

PMID- 8574465
TI  - A phase II trial of continuous-infusion recombinant interleukin-2 in patients
      with advanced renal cell carcinoma: a Southwest Oncology Group study.
AB  - A multicenter, phase II trial of continuous-infusion interleukin 2 (IL-2) was
      done in the Southwest Oncology Group to evaluate the efficacy and safety of this
      treatment in a broad-based population of patients with metastatic renal-cell
      carcinoma. Forty-seven patients from 11 different institutions were entered in
      this study, with 43 eligible. Two technically ineligible patients who received
      treatment and for whom records are available are included in the data analysis.
      Thus, there are 45 analyzable patients. Of these patients, performance status was
      0 in 58% and 1 in 42%. Thirty-one patients had a prior nephrectomy, and 12
      patients had received prior therapy. IL-2 was initially given at a dose of 4.5 x
      10(6) Roche U/m2/day, 4 days a week, for 4 weeks in a row, followed by a 3-week
      rest period. Because of the difficulty in obtaining reimbursement for the
      hospitalization required on the days of IL-2 administration, after 10 patients
      had been entered, the treatment regimen was changed to 6 x 10(6) Roche U/m2/day
      for 4 days as an inpatient, followed by 2 weeks of potential outpatient treatment
      at a dose of 3 x 10(6) Roche U/m2/day for 4 days each week. This was followed by
      a 2-week rest period. Within the 45 analyzable patients, there were 0 complete
      responses and 6 partial responses, for a response rate of 13% (95% confidence
      interval 5.1-27%). Responses occurred in lung metastases, nodal disease, and in
      one patient with bone metastases and the primary kidney tumor. Response durations
      were 1 month, 1 month, 14+ months, 19 months, 26+ months, and 27 months. Of 12
      patients with a nephrectomy and only lung metastases, 4 showed partial responses.
      Medial survival for all analyzable patients is 15 months (95% confidence interval
      8-20 months). Toxicity was significant, with nausea and vomiting, diarrhea, fever
      and chills, dermatologic changes, and fatigue the most frequent. There were 18
      instances of grade 4 toxicity, with the most common grade 4 toxicity,
      respiratory, found in 8 patients. There were two early deaths of probable heart
      related causes while receiving treatment. A continuous-infusion IL-2 regimen that
      allows some potential outpatient treatment shows effectiveness and toxicity
      similar to that in other multicenter IL-2 infusion trials and high-dose
      intravenous bolus regimens.

PMID- 8574466
TI  - Phase I trial of sequential cyclophosphamide, cyclosporin A, and interferon-alpha
      in patients with cancer: attempt to induce autologous graft-versus-host reaction
      to elicit an antitumor response.
AB  - Previous reports of autologous bone marrow transplant (auto-BMT) have
      demonstrated that myeloablative therapy followed by cyclosporin A (CsA), with and
      without interferon (IFN), can generate autoreactive cytotoxic T lymphocytes (auto
      CTL) with potential therapeutic benefit. This is the first report of an attempt
      to generate auto-CTL using CsA and IFN after a non-myeloablative regimen.
      Cyclophosphamide (CTX) 1,200 mg/m2 i.v. day 1 was followed by CsA and IFN-alpha
      days 2-28, administered in a sequential three-step Phase I dose-escalation
      scheme. Patients were evaluated twice weekly for clinical evidence of graft
      versus-host (GVH) reaction. Peripheral blood mononuclear cells (PBMCs) were
      obtained before treatment, at time of clinical GVH reaction, and days 21 and 28,
      and analyzed for auto-CTL, natural killer (NK) cell, and lymphokine-activated
      killer (LAK) cell activity. Patients also underwent punch skin biopsy at the time
      of clinical GVH reaction or day 21 to identify histologic evidence of GVH.
      Fourteen patients completed therapy and were evaluable for immunologic studies
      and anti-tumor response. No increase in auto-CTL, NK cell, or LAK cell activity
      was seen. Clinical or histologic evidence of GVH reaction did not occur. We
      conclude that this myelosuppressive dose of CTX combined with CsA and IFN is
      unable to generate clinical or immunologic evidence of an auto-GVH reaction.
      Further efforts are warranted to evaluate other therapeutic attempts to generate
      auto-CTL with anti-tumor activity based on preliminary results of clinical
      benefit in auto-BMT.

PMID- 8574467
TI  - Severe reversible global and regional ventricular dysfunction associated with
      high-dose interleukin-2 immunotherapy.
AB  - Cardiac toxicity and hemodynamic alterations are frequently associated with high
      dose interleukin-2 (IL-2) immunotherapy in cancer patients. Serious cardiac
      events including myocardial infarction, ischemia, and noninfectious myocarditis
      have been observed. We document two cases of unusually severe but reversible
      cardiac abnormalities related to IL-2 therapy: one patient with a profound form
      of global myocardial hypocontractility and a second patient with regional
      aneurysmal and dyskinetic changes of the left ventricle. These cases exhibit
      unique features not previously described in IL-2-treated patients. The possible
      pathophysiologic mechanisms underlying these global and regional forms of
      cardiomyopathy, including the production of secondary-messenger molecules such as
      nitric oxide and myocardial stunning, are discussed. Both patients remain disease
      free of their cancer (> 3 years since completing therapy), are without residual
      cardiac dysfunction or recurrent related symptoms, and have not experienced any
      additional cardiac events. The report demonstrates the complexity of the cardiac
      toxicities associated with IL-2-based immunotherapy and recognizes a need for
      treating physicians to be familiar with their management.

PMID- 8574468
TI  - Cerebral vasculitis after interleukin-2 therapy for renal cell carcinoma.
AB  - We report one patient with paralysis of the right upper extremity, bilateral
      cerebellar syndrome, and cognitive changes after treatment with interleukin-2 for
      metastatic renal cell carcinoma. Focal neurologic disturbances were associated
      with multiple images of cerebral infarcts but also with extraneurologic signs and
      autoantibodies. We suggest that this is a case of cerebral vasculitis with an
      autoimmune mechanism triggered by interleukin-2 therapy.

PMID- 8574469
TI  - The use of Epstein-Barr virus-transformed B lymphocyte cell lines in a peptide
      reconstitution assay: identification of CEA-related HLA-A*0301-restricted
      potential cytotoxic T-lymphocyte epitopes.
AB  - In the development of cytotoxic T lymphocyte (CTL)-mediated immunotherapy, the
      identification of CTL epitopes is of crucial importance. Binding of a peptide to
      major histocompatibility complex (MHC) class I molecules is one of the
      prerequisites for its function as a CTL epitope. We describe the technique,
      validation, and application of a simple cellular assay, intended for the
      screening of peptides for binding, that can be applied to any human leukocyte
      antigen (HLA) allele. Reconstitution of peptides in MHC class I molecules after
      elution by acid treatment was previously shown to be possible in specially
      engineered cell lines expressing only one type of MHC class I, and was applied
      for the HLA-A*0201 allele. We now report the optimal conditions for application
      of this type of binding assay to the HLA-A*0301 allele. The adaptations that were
      necessary to make the technique operational for HLA-A*0301 are shown in detail.
      These consisted of lowering the pH during acid treatment to 2.9 and lengthening
      the duration of elution to 90 s. Furthermore, immediate aspiration of eluted
      peptides appeared to be essential for this allele. We found also that the use of
      Epstein-Barr virus (EBV)-transformed B cell lines (B-LCL) yields results similar
      to those of the use of cell lines expressing only one specific MHC class I
      allele. Homozygosity for the desired HLA allele improves the sensitivity of the
      assay, but heterozygous cells can also be employed. Finally, we applied this
      technique to a search for HLA-A*0301 binding peptides derived from
      carcinoembryonic antigen (CEA). Of a set of 34 CEA-specific peptides that fit
      with a specified HLA-A*0301-binding motif, we identified a set of six peptides
      with high binding affinity to this allele. These peptides can be regarded as
      potential CTL epitopes.

PMID- 8574470
TI  - Dendritic cells as carriers for a cytotoxic T-lymphocyte epitope-based peptide
      vaccine in protection against a human papillomavirus type 16-induced tumor.
AB  - Previously we have demonstrated that two doses of a cytotoxic T lymphocyte (CTL)
      epitope-based peptide vaccine of human papillomavirus type 16 (HPV 16) E7 aa 49
      57 elicit protection against outgrowth of HPV 16-transformed tumor cells (C3
      cells) in B6 mice. Incomplete Freund's adjuvant (IFA), as a carrier, was used to
      induce this response. To avoid side effects caused by the use of external
      adjuvants, we have now investigated the effectiveness of highly purified spleen
      dendritic cells (DC) that efficiently induce primary peptide-specific CTL
      responses in vitro, as physiological carriers for the HPV 16 E7(49-57) peptide
      based vaccine. This is the first report demonstrating that mice immunized once
      i.v. with syngeneic spleen DCs pulsed with the HPV 16 E7(49-57) peptide in vitro
      were protected against the outgrowth of C3 tumor cells. In comparison, a single
      injection of the HPV 16 E7(49-57) peptide in IFA s.c. also resulted in effective
      induction of tumor-specific immunity in vivo. In both immunization protocols,
      protective tumor-specific immunity was mediated by CTL that recognized HPV 16
      E7(49-57) peptide-pulsed target cells, as well as C3 cells in vitro. Peptide
      affinity of the CTL induced by both protocols was similar. Thus under the
      conditions tested, a single injection of spleen DCs pulsed with a CTL epitope
      based peptide in vitro elicited tumor-antigen-specific CTL in vivo, which
      protected mice against a subsequent tumor inoculation. This result indicates that
      spleen DCs pulsed with a CTL epitope can effectively serve as a tumor-specific
      vaccine.

PMID- 8574471
TI  - Preclinical evaluation in nonhuman primates of an anti-idiotypic antibody that
      mimicks the carcinoembryonic antigen.
AB  - We have developed and characterized a murine monoclonal antiidiotype (Id)
      antibody (Ab2), designated 3H1 (IgG1-k) that mimics human carcinoembryonic
      antigen (CEA). 3H1 was raised against an anti-CEA monoclonal antibody (mAb) 8019
      (Ab1) that recognizes a distinct and specific epitope of the 180,000 MW CEA. 3H1
      induced specific anti-CEA immune responses in mice and rabbits. In this
      preclinical study, cynomolgus monkeys (Macaca fascicularis) were immunized with
      aluminum hydroxide-precipitated 3H1 and tested for the induction of anti-CEA
      antibodies. Monkeys were injected with 2 mg of 3H1, intracutaneously, four times
      biweekly. All monkeys developed specific anti-anti-Id (Ab3) responses that were
      capable of inhibiting binding of the immunizing 3H1 (Ab2) to 8019 (Ab1) and vice
      versa. Furthermore, immune sera from monkeys contained Ab3 (Abl') antibody that
      bound to CEA-positive colon carcinoma cell lines but not to CEA-negative MOLT-4
      or melanoma cell lines. Also, the Ab3 reacted with purified CEA and competed with
      Ab1 (8019) for binding to CEA positive LS174-T cells, suggesting that Ab1 and Ab3
      may bind to the same epitope. In addition, affinity-purified Ab3 from monkey sera
      immunoprecipitated the same 180,000 MW CEA as Ab1 8019 and showed an identical
      pattern as the Ab1 on colon carcinoma specimens by immunoperoxidase staining. The
      induction of anti-tumor antibodies in monkeys did not cause any apparent side
      effects. These data suggest that internal image anti-Id can induce tumor-specific
      humoral immune responses in nonhuman primates and can serve as potential network
      antigen for triggering active anti-CEA antibodies in colorectal cancer patients.

PMID- 8574472
TI  - [Health promotion, a primary aim in nursing].

PMID- 8574473
TI  - [Naomi Feil enchants us with "validation". Interview by Elisabeth von Samson and
      Claudia Bokeloh].

PMID- 8574474
TI  - [Federal Hospital Conference in Bonn. The legislation for nursing personnel must
      remain].

PMID- 8574475
TI  - [Finding ways to be more effective].

PMID- 8574476
TI  - [Continuing education as a hygiene specialist].

PMID- 8574477
TI  - [The clown's office hours in the hospital. Soul doctor with a red nose and a
      floppy hat].

PMID- 8574478
TI  - [Stoma care; more than just changing the pouch].

PMID- 8574479
TI  - [Rehabilitation after head injuries. Mostly young people are involved].

PMID- 8574480
TI  - [The problematic right to death with dignity. 2. Problem cases with assisted
      dying].

PMID- 8574481
TI  - [Dying in the hospital. II. Our own feelings about dying and death].

PMID- 8574482
TI  - [From discussion to counseling to supervision. We have to learn to listen].

PMID- 8574483
TI  - [Outline for continuing education in psychiatric nursing].

PMID- 8574484
TI  - [Care of osteoporosis has to pay attention to nutrition].

PMID- 8574485
TI  - [Academization of nursing. The need for academically trained nurses is
      increasing].

PMID- 8574486
TI  - [Report on experiences from the other side. Anxieties of a nurse as patient].

PMID- 8574487
TI  - [Systematic food distribution saves 11 minutes daily].

PMID- 8574488
TI  - Developments in hepatitis epidemiology: hepatitis C virus.

PMID- 8574489
TI  - Splanchnic blood flow and multiple organ failure.

PMID- 8574490
TI  - Home nebuliser-compressors.
AB  - Home nebuliser therapy requires sensible supervision to ensure that the nebuliser
      and the compressor are well matched and that both are in good condition. It can
      then be acceptable and helpful to appropriately selected patients.

PMID- 8574491
TI  - Drug-resistant tuberculosis: mechanisms and management.
AB  - Infection with Mycobacterium tuberculosis remains a major global health problem
      and the recent outbreaks of multidrug resistant (MDR) tuberculosis have been a
      major cause for concern. An accurate picture of the extent of this problem is not
      possible because only a limited number of countries have reliable surveillance
      programmes. However, the experience in the USA reinforces the need for strict
      adherence to standard public health measures and good clinical practices to
      minimise the impact of MDR tuberculosis in the human immunodeficiency virus era.

PMID- 8574493
TI  - Transabdominal cervical cerclage.
AB  - Cervical cerclage is a procedure carried out to increase the fetal salvage rate
      in women with a history of previous miscarriages. This article discusses the
      merits of transabdominal cerclage as opposed to the more usual procedure of
      transvaginal cervical cerclage.

PMID- 8574492
TI  - Practical management of treatment-resistant affective disorders.
AB  - The Geoffrey Knight National Unit was set up in 1970 exclusively for
      psychosurgery. In recent years it has become increasingly concerned with the
      development of medication regimens that might avoid the need for surgery. This
      has offered a unique pharmacotherapeutic opportunity because all the referrals
      have severe, persistent and treatment-resistant disorders. The scheme of high
      dose and combined medication devised is presented and discussed.

PMID- 8574494
TI  - Anaesthetic dilemma: half a spinal is better than none.

PMID- 8574495
TI  - Clinical pharmacology and classification of antiarrhythmic drugs.
AB  - Despite major contemporary strides in the treatment of cardiac arrhythmia, the
      bedrock for many patients management is still rooted in chronic drug therapy. In
      the last 10 years considerable changes in patterns of drug use has affected every
      aspect of these agents down to the basic level of drug classification and
      assessment of their clinical pharmacology. This review looks at the systems of
      antiarrhythmic drug classification currently used and the rationale for adopting
      newer approaches.

PMID- 8574496
TI  - Elderly people who fall: identifying and managing the causes.
AB  - Falls are not a mundane and inevitable consequence of ageing, but are a serious
      threat to the health and the independence of many older people. There is now very
      good evidence that the risk of falls can be significantly lowered by careful
      clinical evaluation and institution of a physical retraining programme.

PMID- 8574497
TI  - Drug removal in continuous haemofiltration and haemodialysis.
AB  - Although both continuous haemofiltration and continuous haemodialysis are
      techniques routinely employed in the management of critically ill patients,
      deciding on a drug dosing regimen is often difficult. This article highlights the
      factors influencing drug removal by both processes, the difficulties associated
      with the interpretation of research in this area and offers a number of
      approaches which can be used when selecting a dosing regimen for a patient
      receiving one of these therapies.

PMID- 8574498
TI  - Acinic cell carcinoma of the parotid in a child presenting as a pre-auricular
      cyst.

PMID- 8574499
TI  - The use of Healthcare Resource Groups in managing clinical resources.
AB  - Healthcare Resource Groups are a way of aggregating together patient treatment
      episodes that are similar in their resource consumption. They can be derived from
      existing minimum dataset information. In England, they are being used to provide
      costs for contract pricing and can also be used to provide comparisons of the
      efficiency of use of hospital beds. This article describes their development and
      construction and discusses the potential use and further development.

PMID- 8574500
TI  - ECCO-8: mapping the future in oncology.

PMID- 8574501
TI  - Adaptive control of drug dosage regimens using maximum a posteriori probability
      Bayesian fitting.
AB  - Optimal drug therapy can only be achieved if a drug is given in the right dosage
      regimen. Therefore the dosage regimen needs to be optimized, using the available
      information of the drug, the patient, and his disease. The optimization of drug
      therapy comprises two major steps: First, the clinician should define explicit
      therapeutic goals for each patient individually. Second, a strategy to achieve
      these goals with the greatest possible precision should be chosen. An overview of
      the optimization of drug therapy is presented, with special reference to maximum
      a posteriori probability (MAP) Bayesian fitting. Drug dosage optimization
      requires 1. measurement of a performance index related to the therapeutic goal,
      generally one or more plasma concentration measurements, 2. population
      pharmacokinetic parameters, including mean values, standard deviations,
      covariances and information on the statistical distribution, and 3. reliable
      software for adaptive control strategy and optimal dosage regimen calculation.
      The benefit of optimal drug therapy by adaptive control using MAP Bayesian
      fitting has been proven, resulting in improved patient outcome by improved
      efficacy of therapy and a reduction of adverse reactions, and in reduced costs,
      mainly due to a reduction of hospitalization. Newer strategies might replace the
      MAP Bayesian fitting procedure, if their advantage has been demonstrated
      convincingly, and if reliable and user-friendly software is available.

PMID- 8574502
TI  - Aminoglycoside pharmacokinetics and -dynamics: a nonlinear approach.
AB  - A model which correctly describes the pharmacokinetic-pharmacodynamic
      relationship is necessary to perform a rational pharmacotherapy. This model could
      predict the effects under variable conditions. The prediction will provide a
      basis for adapting therapy to individuals. A nonlinear model should be most
      appropriate for describing drug effects. A new model, containing nonlinear
      pharmacokinetics and pharmacodynamics, is presented to describe effects of
      aminoglycosides on bacterial growth and accumulation in kidney tissue.

PMID- 8574503
TI  - Duration of opioid antagonism by nalmefene and naloxone in the dog. A
      nonparametric pharmacodynamic comparison based on generalized cross-validated
      spline estimation.
AB  - The opioid antagonist nalmefene was compared in its pharmacodynamic properties to
      the structurally similar antagonist naloxone in a 2 x 2 cross-over study with 8
      dogs. Opioid-induced respiratory depression was produced for ca. 7 hours with a
      constant rate intravenous infusion of 30 micrograms/kg/hr fentanyl and quantified
      using noninvasive transcutaneous pCO2 recordings. Upon reaching a pseudo-steady
      state of respiratory depression at 2 hours post fentanyl infusion initiation, the
      animals then received either nalmefene (12 micrograms/kg/hr) or naloxone (48
      micrograms/kg/hr) for 30 minutes. The pharmacodynamic pCO2 responses produced by
      the combined agonist/antagonist regimen were fitted with a cubic spline function
      using a generalized cross-validation technique. Various quantities that describe
      the onset, duration and relative potency of each antagonist were determined
      directly from the estimated response curves in a model-independent, nonparametric
      way. The 2 antagonists were compared in terms of these quantities using a
      statistical model that considers carry-over effects typically arising from a
      possible development of tolerance. The results indicate that nalmefene: 1. is
      approximately 4-fold more potent than naloxone, 2. has an onset of reversal as
      rapid as naloxone, and 3. has a significantly longer (2-fold) pharmacodynamic
      duration of action than does naloxone. The mean time required for the agonist to
      regain 30% or 50% of its effect present at the start of the antagonist infusion
      was 66 and 112 minutes and 37 and 55 minutes for nalmefene and naloxone,
      respectively. Early, effective pharmacodynamic screening of new drug compounds is
      a valuable way of accelerating the drug discovery process and reducing escalating
      drug development costs. This study exemplifies a novel, endpoint oriented
      pharmacodynamic comparison procedure that can be done expeditiously before
      starting the time consuming development and validation of a drug level assay, and
      before engaging in considerably more involved integrated PK/PD studies.

PMID- 8574504
TI  - Unifying concept of pharmacokinetics derived from drug distribution and
      elimination in renal failure.
AB  - We are in the process of establishing a pharmacokinetic database for drug dosage
      adjustment to impaired renal function. To meet these demands, the system needs a
      unifying pharmacokinetic concept. Drug clearance is the common parameter that
      allows for intersecting the different pharmacokinetic approaches. In addition,
      two parameters are essentially needed for the concept, either the area-derived
      volume and the dominant elimination half-life or the moment-derived volume and
      the mean residence time. For drugs where the area-derived volume decreases with
      renal impairment, it can be shown that compartment-derived parameters are
      explicitly convertible into moment-derived parameters and vice versa.

PMID- 8574505
TI  - Pharmacokinetic-pharmacodynamic and metabolite modeling with TopFit.
AB  - Two examples illustrating the ease of use and powerful data fitting and
      simulation techniques provided by the validated program TopFit 2.0 for the PC are
      presented. In the first, kinetics of parent compound and metabolite for (+) and (
      ) enantiomers of a racemic compound X were determined during a Phase III clinical
      study. Four data sets were fitted simultaneously for each patient. The model
      could be defined by the user without programming differential equations. The fit
      results indicated enantiomer specific kinetics for the metabolite but not for
      parent compound. In the second example, a model with nonlinear elimination and an
      Emax-effect function was used to simultaneously fit data from six doses of
      compound Y in a Phase I study. The fitted parameters predicted the feasibility of
      a twice-daily dose regimen despite a very short plasma half-life of the compound.
      In conclusion, TopFit provides rapid and cost-effective support in analysis and
      design of clinical trials.

PMID- 8574506
TI  - Analysis of errors due to assigned model constants in pharmacokinetic
      calculations based on functional optimization.
AB  - Mathematical models in pharmacokinetic studies frequently include, in addition to
      model parameters that are estimated from experimental data, model constants that
      are directly measured or derived from standardized, anthropometric formulae.
      Although these assigned constants are usually considered as error-free,
      uncertainties in their values affect the estimation precision of the remaining
      model parameters as well as the reliability of other derived quantities such as
      predictions of drug concentration levels or prescriptions of drug dosage. The
      present paper addresses the problem of quantifying the effects of errors in
      assigned model constants on the outcome of pharmacokinetic calculations. The
      error analysis is performed starting from the general assumption that the
      optimization of some objective function, such as encountered in parameter
      estimation, is involved. The proposed approach is based on the linearization of
      theoretical conditions that must be satisfied by the optimal solution of the
      problems. It requires quite complex mathematical calculations which can be
      however performed automatically by specific software based on symbolic computer
      algebra. Examples of applications are reported showing the usefulness of this
      kind of error analysis, in particular for detecting potentially critical error
      sources in the modeling of physiological systems and for suggesting improvements
      to experimental protocols for increasing the confidence in diagnostic and
      therapeutic decisions.

PMID- 8574507
TI  - NONMEM analysis in determining the tri-exponential disposition of cefotaxime: a
      method of evaluating serum and urinary phase I data.
AB  - The time above the minimum inhibitory concentration (MIC) is an important
      surrogate parameter for the efficacy of cephalosporines. In clinical practice
      cefotaxime (CTX) is usually administered every 8 h or 12 h. Unfortunately the
      limit of quantification (LOQ) of the available assay is not low enough to detect
      CTX concentrations in serum later than 6 h after a 2 g i.v. dose. Consequently
      the time above MIC has to be estimated by extrapolation of the available serum
      data. Due to the concentrating properties of the kidney, concentrations in urine
      following a 2 g dose however remain above the LOQ for up to 16 h. It is therefore
      possible to follow the pharmacokinetics of CTX in urine within a 12 h dosing
      interval. Due to the linear pharmacokinetics of CTX, serum concentrations, and
      accordingly the time above MIC, can be estimated by using the measured urinary
      excretion and the calculated renal clearance. The pharmacokinetics of cefotaxime
      were studied in 12 healthy subjects who received a single 2 g i.v. dose
      administered as a short infusion. Blood and fractional urine were collected up to
      24 h after dosing. For the characterization of the true terminal half-life only
      sparse and unbalanced serum and urinary data was available. In such situations,
      the population approach is the method of choice for estimating the kinetic
      parameters. The combined analysis of serum and urinary data using NONMEM shows
      the superiority of a tri-exponential compared to a bi-exponential
      pharmacokinetics model. As a result, the predicted serum trough levels of
      cefotaxime following twice daily dosing are about 30-fold higher than those
      extrapolated from the bi-exponential model. Consequently, the concentrations of
      CTX- and its metabolite desacetyl-CTX--are above the MIC of many therapeutically
      relevant pathogens for a longer period of time than previously assumed. In
      conclusion, a twice daily dosing regimen for cefotaxime is adequate for a number
      of clinically relevant pathogens. This is supported by the positive outcome in
      previous clinical trials following this dosing regimen.

PMID- 8574508
TI  - Computation of the initial distribution of a drug by repetitive convolution with
      a circulatory transport function.
AB  - Hereby we present a widely applicable computational method for the description of
      recirculation and distribution phenomena occurring immediately after intravenous
      injection of a substance. The intravascular concentration-time course, r, is
      described as r = c0 + g * r, where the asterisk denotes the convolution
      operation, c0 is the concentration-time course during the first passage of the
      substance at an arterial measuring site and g is the transport function of the
      body. If the body transport function is known, then the arterial concentration
      time course of a substance can be predicted for different amounts, injection
      times and elimination rates. The site of interest can be chosen arbitrarily, i.e.
      the concentration-time course in the arterial circulation supplying any organ can
      be described. This might be of special interest for the optimal design of
      intravenous injections of contrast media, where initial concentrations at the
      region of interest determine the success of the diagnostic procedure.

PMID- 8574509
TI  - Postprandial bile-duct kinetics under the influence of 4-methylumbelliferone
      (hymecromone).
AB  - The physiological correlate of biliary colic is a rapid increase in pressure in
      the presence of biliary obstruction. The relaxing action of hymecromone on the
      biliary tract provides a pharmacotherapeutic approach. As the symptoms usually
      occur postprandially we used ultrasonography to examine whether hymecromone was
      able to reverse the contraction of the common bile duct (CBD) after ingestion of
      a standardized test meal. The study was designed as prospective, double-blind
      randomized crossover study versus placebo in 20 healthy volunteers. The width of
      the CBD was measured ultrasonographically in the fasting subjects and at 1, 3, 5,
      10, 15 and 20 minutes after ingestion of a test meal. Then the subjects were
      given either 400 mg of hymecromone or placebo and the measurement series was
      repeated. After ingestion of the test meal the width of the CBD decreased by a
      maximum of 20% after 15 minutes. While there was only a slight increase in the
      width of the CBD after subsequent administration of placebo, a maximum increase
      of 36% was measured 10 minutes after administration of hymecromone. The
      postprandial contraction of the CBD can be reversed within a short time by i.v.
      administration of hymecromone.

PMID- 8574510
TI  - Pharmacokinetics, safety and tolerability of the orally administered receptor
      antagonist of cysteinyl-leukotrienes BAY x 7195 in single-dose escalation
      studies.
AB  - BAY x 7195 is a novel receptor antagonist of cysteinyl-leukotrienes currently
      under development for the treatment of asthma. It is effective in antagonizing
      the leukotriene-D4 induced bronchoconstriction in healthy volunteers following
      oral administration. The pharmacokinetics, safety and tolerability of the drug
      were investigated in six partially placebo-controlled studies in healthy
      volunteers with single oral administration of a 50, 100, 250, 500 and 1000 mg
      dose as a tablet. The drug was well tolerated. The only remarkable adverse event
      was diarrhea in one volunteer receiving the highest dose of 1000 mg. There were
      no additional clinically relevant changes in any safety parameter including
      laboratory values. Concentrations of BAY x 7195 were determined in plasma and
      urine by high performance liquid chromatography with fluorescence detection and
      plasma-concentrations were further evaluated by compartmental and non
      compartmental methods. The concentration vs time profiles of the drug were
      biphasic with a dominant t1/2 of 0.5-2 h and a terminal t1/2 of 5-10 h.
      Pharmacokinetics were linear in the investigated range of doses. In spite of
      substantial inter-subject variability intra-individual variability in AUC and
      Cmax was reasonable. In general, the concentration vs time profiles could be
      described with a 2-compartment body model. However, in some cases the occurrence
      of second and third concentration maxima necessitated the use of a multiple
      segment absorption model to accomplish a good fit to the data. Enterohepatic
      recirculation following glucuronidation of the drug is the likely reason for the
      multiple peaks. Urinary excretion of BAY x 7195 and its glucuronide metabolite
      was negligible the amount excreted into urine from 0 to 48 h being < 0.1% of the
      dose. The low renal clearance of BAY x 7195 (< or = 0.07 ml/min) is suggestive of
      significant reabsorption in the renal tubuli taking into account that the
      expected renal clearance for a drug with 99.5% protein binding is about 0.6
      ml/min.

PMID- 8574511
TI  - A new route, jet-injection for anesthetic induction in children: I. Midazolam
      dose-range finding studies.
AB  - In order to assure rapid anesthetic induction in children and to prevent the
      psychological and physical trauma associated with restraint during mask induction
      or intramuscular injection, we evaluated the utility of a jet-injector and the
      effectiveness of midazolam for anesthetic co-induction in a dose-range finding
      study. Forty children (age: 1-6 yrs), whose parents gave a valid consent approved
      by the Institutional Review Board (IRB) and who underwent minor surgery, were
      randomized into four equal groups: A. midazolam 100 micrograms/kg by jet
      injection (JI); B. midazolam 150 micrograms/kg JI; C. midazolam 200 micrograms/kg
      JI; D. midazolam 80 micrograms/kg i.m by conventional syringe-needle. As a drying
      agent, atropine 20 micrograms/kg JI or i.m. was also added to the midazolam
      solution. The onset and full sedative effect of midazolam, the scoring of
      sedation and emotional state, the ease of placement of the intravenous catheter,
      the speed of recovery by Aldrete-scores and the time for safe discharge were
      evaluated. No demographic differences were observed among the four groups with
      similar mean duration of surgery and anesthesia. The mean sedation score was
      reduced in Group C the most, less in the B, A and D groups. The onset of sedation
      ranged from 3-5 min in groups A, B or C as compared to 5-9 min in D. Ideal
      conditions for the start of i.v. catheter were best achieved in group C (8:8) and
      B (8:10) in contrast to groups A (2:10) and D (0:10). Whereas no i.v. start was
      difficult in B and C, 6:10 were difficult in D and A. None of the children in the
      three JI groups (A, B and C) experienced unpleasant recall or pain from the
      injection during the whole procedure. Response to verbal stimuli recovered in 3
      min after the end of anesthesia and the children were discharged 8-9 minutes
      afterward. None of the children needed a longer than 15-minute interval to reach
      an Aldrete score of 10. No differences among the groups were observed as to the
      time of recovery or discharge. This new route of midazolam administration with
      the jet-injector allows pain-free and stress-free induction of anaesthesia after
      rapid placement of an intravenous catheter and prevents the transmission of
      infections.

PMID- 8574512
TI  - Prepilin-like molecules in type 4 pilus biogenesis: minor subunits, chaperones or
      mediators of organelle translocation?

PMID- 8574513
TI  - The scope for virulence management: a comment on Ewald's view on the evolution of
      virulence.

PMID- 8574514
TI  - Animal models of protective immunity in tuberculosis to evaluate candidate
      vaccines.
AB  - While the etiology of tuberculosis is well understood, the nature of the
      protective immune response to the causative mycobacteria has remained a mystery.
      There is an urgent need to define protective immunity critically, and to develop
      alternative animal models to evaluate the efficacy of new-generation vaccines
      against tuberculosis in a cost-effective way.

PMID- 8574515
TI  - Role of viruses in the loss of tolerance to self-antigens and in autoimmune
      diseases.
AB  - The breaking of tolerance to self-antigens, involving the activation of self
      reactive lymphocytes, is a critical event leading to autoimmune disease. The
      precise mechanisms by which this occurs are unknown, but among other etiological
      factors, viruses have been implicated. Recent results with animal models of
      insulin-dependent diabetes provide insight into how viruses induce autoimmune
      disease.

PMID- 8574516
TI  - Porphyromonas gingivalis: a proteinase/gene accounting audit.
AB  - Analysis of the available data on the Porphyromonas gingivalis proteinase system
      suggests that at most three different genes encode arginine-X- and lysine-X
      specific cysteine proteinases. These are synthesized as polyproteins containing a
      prepropeptide, a catalytic domain and a hemagglutinin domain. Post-translational
      processing of each precursor is responsible for the variety of proteinase forms
      that are seen.

PMID- 8574517
TI  - Early events in infection of lymphoid tissue by a lentivirus, maedi-visna.
AB  - All members of the lentivirus family infect cells of the monocyte-macrophage
      lineage, although this may be obscured during infection in vivo by the effect of
      the virus on other cells, such as CD4+ lymphocytes. Macrophages are the major
      cell type infected by the ruminant lentivirus maedi-visna, making it a valuable
      model for studying the pathogenesis of lentiviruses in these cells.

PMID- 8574518
TI  - Potential for erythromycin resistance in porcine Campylobacter species.

PMID- 8574519
TI  - In vitro models of the blood-brain barrier to study bacterial meningitis.
AB  - In vitro models of the blood-brain barrier involving culturing cerebral
      microvascular endothelial cells may provide information critical to understanding
      diseases of the central nervous system, such as bacterial meningitis, that would
      be difficult to obtain from clinical studies or from in vivo models. These models
      may also identify targets for therapeutic intervention.

PMID- 8574520
TI  - Hepatitis C virus quasispecies populations during chronic hepatitis C infection.
AB  - Hepatitis C virus populations in infected individuals consist of quasispecies
      with diverse mutations. These quasispecies have different biological properties,
      and the analysis of these variants has led to new interpretations of viral
      persistence, carcinogenesis and resistance to interferon therapy.

PMID- 8574521
TI  - Mechanism for antigen detection on deplasticized epoxy sections.
AB  - The purpose of this investigation was to explain why deplasticizing of epoxy
      sections gives higher immunogold labeling than non-deplasticizing. The methods
      used were the following: (1) Comparison of the ratio of immunogold labeling of
      deplasticized and non-deplasticized sections with gold particles of different
      sizes and comparison of this ratio with respect to sections of different
      thickness, (2) the tilt method (Brorson et al., 1994). Human kidney tissue with
      amyloid A depositions, human fibrin, and human pituitary tissue were embedded,
      sections were deplasticized on grids, treated with anti-Aa, anti-fibrinogen or
      anti-ACTH (ACTH = adrenocorticotropic hormone), and reembedded on grids.
      Indications of significant antibody penetration were found only at the periphery
      of structures (ACTH-vesicles). This penetration was about 30 nm. The ratios of
      immunogold labeling of deplasticized and non-deplasticized sections were
      approximately 2, 5 and 1 for amyloid, fibrin and ACTH, respectively, and were
      independent of the gold particle size. No significant differences of gold
      labeling were found between thicker and thinner deplasticized epoxy sections
      regardless the gold particle size. No significant differences of gold labeling
      between deplasticized epoxy sections and LR-White sections were found on interior
      areas of ACTH-vesicles or amyloid A plaques. The increased labeling of
      deplasticized epoxy sections compared to normal epoxy sections seemed to be
      mainly a surface phenomenon. The practical significance of this observation is
      that deplasticizing of epoxy sections may be a better method for localizing
      antigens at the periphery of structures than the use of other resin embedding
      media. Deplasticizing of epoxy sections may be a method of choice in a
      pathological laboratory to detect antigens in routinely embedded tissues.

PMID- 8574522
TI  - A scanning tunnelling microscopic study of site-specifically immobilized
      immunoglobulin G on gold.
AB  - A convenient and efficient method for the site-specific incorporation of foreign
      cysteine residues at the C-termini of immunoglobulin G (IgG) using
      carboxypeptidase-Y-catalyzed transpeptidation is explored as a means of ensuring
      oriented immobilization of IgG on gold. A scanning tunnelling microscopic study
      of the immobilization of the modified IgG molecules on gold surfaces is reported.
      The results show not only that some globular features are observed to form
      striking surface patterns with a geometric size close to that of the fragments of
      IgG but also that the conformation of the bound IgG molecules appears more stable
      when adsorbed on gold. The effect of the immobilization method on these
      topographic features is discussed.

PMID- 8574523
TI  - The nuclear status of human sperm cells.
AB  - In the last decade, and in particular since the development of in vitro
      fertilization techniques, the nuclear status of human sperm cells has shown to be
      a key parameter in the assessment of male fertility. The shape and condensed
      state of the mature sperm nucleus are determined by structural and functional
      events that occur during spermiogenesis. This paper reviews essential findings on
      re-organization of the nucleus during sperm differentiation and maturation, and
      reports recent data on the architecture, biochemical composition and stability of
      the nucleus in human ejaculated spermatozoa. Different methods used to evaluate
      nuclear maturity in relation to male fertility are critically appraised.

PMID- 8574524
TI  - Scanning probe microscopy in microbiology.
AB  - Scanning probe microscopy (SPM) is emerging as an important alternative to
      electron microscopy as a technique for analyzing submicron details on biological
      surfaces. Microbiological specimens such as viruses, bacteriophages, and ordered
      bacterial surface layers and membranes have played an important role in the
      development of scanning tunnelling microscopy (STM) and atomic force microscopy
      (AFM) in cellular and molecular biology. Early STM studies involving metal-coated
      bacteriophage T4 polyheads, Methanospirillum hungatei, and Deinococcus
      radiodurans HPI layer clearly demonstrated that resolution was comparable to TEM
      on similarly prepared specimens and only limited by metal graininess. However,
      except for thin films or layers, novel biological information has been difficult
      to obtain since imaging native surfaces of such biomaterials as proteins or
      nucleic acids by STM proved to be unreliable. With the development of atomic
      force microscopes, which allow imaging of similar native structures, SPM
      applications have widened to include straightforward surface structure analysis,
      analysis of surface elastic and inelastic properties, bonding force measurements
      between molecules, and micro-manipulations of such individual molecules as DNA.
      AFM images have progressed from relatively crude representations of specimen
      topography to nanometer scale representations of native hydrated surfaces. It
      appears from the study of microbiological specimens that direct visualization of
      dynamic molecular events or processes may soon become a reality.

PMID- 8574525
TI  - Reporting standards and statistics for evaluating intervention.

PMID- 8574526
TI  - Cytokine therapy for arterial restenosis: inhibition of neointimal hyperplasia by
      gamma-interferon.
AB  - Inhibition of neointimal hyperplasia by gamma-interferon (gIFN) treatment was
      evaluated. Four groups of Sprague-Dawley rats (n = 72) weighing 500 g underwent
      endothelial injury of the carotid artery using the previously described Fogarty
      catheter technique. Group I (controls, n = 8) received one phosphate-buffered
      saline (PBS) injection 24h before injury and every 24h thereafter for a total of
      eight injections. Groups II (n = 8) and III (n = 8) received daily injections of
      200,000 units of gIFN according to the same schedule except that group III did
      not receive the preoperative dose. Animals were killed on postoperative day 14.
      Histologic sections were analyzed morphometrically and immunohistochemically.
      Both gIFN groups had a statistically significant 50% reduction of the cross
      sectional area of the neointimal hyperplasia compared with that of the controls
      (P < 0.01). Cell replication analysis of smooth muscle cells in the media and
      neointima revealed no statistically significant difference between controls and
      gIFN-treated groups. Group IV consisted of 48 rats that were treated with either
      PBS or gIFN on a schedule similar to that of groups I and II. Animals were killed
      at frequent time intervals during the first 7 days after injury. Their arteries
      were analyzed histologically and immunohistochemically. The results confirm
      previous findings that gIFN reduces the development of neointimal hyperplasia
      following arterial injury. The results also indicate that smooth muscle cells
      restore their proliferative activity by 7 days after discontinuation of gIFN
      treatment. It is proposed that efficacy of gIFN can be enhanced by lengthening
      the period of treatment.

PMID- 8574527
TI  - Differential mechanisms of failure of autogenous and non-autogenous bypass
      conduits: an assessment following successful graft thrombolysis.
AB  - The advent of graft thrombolysis has provided an objective means for evaluating
      the etiology of graft occlusion. Over a 10-year period, intra-arterial urokinase
      (102 cases) or streptokinase (seven cases) was used in 109 infrainguinal conduits
      (30 autogenous and 79 non-autogenous) that failed 30 days or more after
      implantation. Thrombolysis was not achieved in 19 additional graft occlusions;
      these cases were excluded from study because of an inability to define the
      mechanism of failure. Non-invasive laboratory data were available within 6 months
      of graft occlusion in 82 (75%) of the cases, with Doppler segmental studies in 80
      cases (73%) and duplex ultrasonography studies in 39 cases (36%). Pre-failure non
      invasive laboratory abnormalities were detected more frequently in autogenous
      grafts (21 of 24 patients, 88%), while non-autogenous grafts usually occluded
      without prior hemodynamic change (11 of 58 patients had abnormalities, 19%) (P <
      0.001). Thrombolysis uncovered anatomic defects responsible for thrombosis in 27
      (90%) of 30 autogenous grafts compared with only 32 (41%) of non-autogenous
      conduits (P < 0.001). The most common lesions underlying autogenous graft failure
      comprised stenoses within the body of the graft (11 cases, 37%), while the most
      common lesions in failed non-autogenous grafts appeared to be stenoses at an
      anastomosis (21 cases, 27%). Thus, the mechanisms underlying the late failure of
      autogenous and non-autogenous grafts differ markedly; autogenous grafts most
      commonly fail as a result of the gradual development of lesions intrinsic to the
      graft, while non-autogenous grafts fail precipitously, presumably as a result of
      some non-anatomic mechanism.

PMID- 8574528
TI  - Long QT syndrome: an indication for cervicothoracic sympathectomy.
AB  - Beta-blockade represents the primary treatment modality in patients with long QT
      syndrome, but left cervicothoracic sympathectomy (LCS) has been employed in
      refractory cases and in cases with malignant arrhythmias. LCS was performed in
      ten patients (six male, four female) with long QT syndrome, ranging in age from 1
      month to 40 years (median 15 years). Familial long QT syndrome was present in
      seven patients (70%). The mean(s.e.m.) (range) preoperative corrected QT interval
      (QTc) was 0.52(0.01) (0.46-0.60)s. The mean(s.e.m.) duration of symptoms was
      4.4(1.1) years with a mean(s.e.m.) of 4.1(0.9) syncopal episodes and 1.2(0.2)
      cardiac arrests per patient. LCS was carried out for refractory symptoms on beta
      blockers in nine cases; a single patient was unable to tolerate beta-blockers and
      LCS represented the primary treatment modality. A left supraclavicular approach
      was utilized in each patient, resecting a portion of the stellate and all of the
      T2 and T3 ganglia. The median(range) length of hospitalization following
      operation was 2(2-6) days. There were no unexpected complications of operation,
      although nine (90%) of the patients developed Horner's syndrome. The QTc
      decreased a mean(s.e.m.) of 0.03(0.01)s following operation (P < 0.01). The
      frequency of symptomatic episodes decreased from a mean(s.e.m.) of 7.1(3.1)/year
      before LCS to 0.1(0.1) after operation (P < 0.001). Patients have been followed
      for a mean of 1.3(0.3) years, and all but one patient remains symptom-free; the
      youngest patient died suddenly 10 months after surgery. These results suggest
      that LCS is associated with significant clinical benefits in patients with long
      QT syndrome and the procedure should be considered when symptoms are refractory
      and malignant, or when contraindications to beta-blockers are present.

PMID- 8574529
TI  - Composite porosity of expanded polytetrafluoroethylene vascular prosthesis.
AB  - Polytetrafluoroethylene (PTFE) prostheses were modified to produce two types of
      composite porosity PTFE grafts: type I--inner 60 microns/outer 20 microns and
      type II--inner 20 microns/outer 60 microns. These composite porosity PTFE designs
      were investigated for bleed through, graft healing and patency and compared with
      high porosity PTFE (60 microns) and standard PTFE (20 microns) grafts. The grafts
      were implanted into the carotid and femoral arteries of dogs and retrieved after
      4, 12 and 18 weeks. Both composite porosity grafts showed significantly less
      bleed through than standard and high porosity grafts after reperfusion. In
      composite grafts, the 60-microns layer allowed fibrovascular tissue and
      histiocyte ingrowth from perigraft tissue, but the 20-microns layer did not.
      Neointima formation occurred earlier and endothelialization was more extensive in
      high porosity grafts, but seroma formation occurred in 25% of cases. In type I
      composite porosity grafts, smooth muscle cells of neointima migrated into the
      pores of the graft, providing a firmly anchored intima. Type II composite
      porosity grafts allowed better ingrowth of fibrovascular tissue at the outer
      layer from the perigraft tissue; however, endothelialization was not completed.
      Composite porosity grafts should be considered for evaluation in specific
      clinical situations.

PMID- 8574530
TI  - Recurrent varicose veins following high ligation of long saphenous vein: a duplex
      ultrasound study.
AB  - Duplex scanning was used to study recurrent varicose veins in 244 limbs with
      previous high ligation of the long saphenous vein. The recurrent varicose veins
      were classified into two types according to the presence or absence of a residual
      long saphenous vein. Varicose veins with a residual long saphenous vein (type I)
      occurred in 168 limbs (68.9%). A residual long saphenous vein with an incompetent
      saphenofemoral junction was present in 125 limbs and one without any residual
      saphenofemoral junction in 43 limbs. Besides the presence of an incompetent long
      saphenous vein in this group, an incompetent short saphenous vein was detected in
      26 limbs, incompetent perforating vein(s) in 45 limbs and incompetent deep veins
      in 26 limbs. Varicose veins without a residual long saphenous vein (type II)
      occurred in 76 limbs (31.1%). An incompetent short saphenous vein was
      demonstrated in 44 limbs, incompetent perforating vein(s) in 18 limbs and
      incompetent deep veins in 32 limbs. Of the total 244 limbs with recurrent
      varicose veins, long saphenous vein incompetence was involved in 168 (68.9%),
      short saphenous vein incompetence in 70 (28.7%), perforating vein incompetence in
      63 (25.8%) and deep venous incompetence in 58 (23.8%). Although saphenofemoral
      junction incompetence was found to be the main source of recurrence, a segment of
      incompetent residual long saphenous vein, an incompetent short saphenous vein,
      perforating vein and deep venous system incompetence are other common sources of
      recurrence. A precise assessment to identify underlying venous incompetence is
      important for the management of recurrent varicose veins.

PMID- 8574531
TI  - Dosage and timing of Photofrin for photodynamic therapy of intimal hyperplasia.
AB  - Photodynamic therapy has been recommended as a method of preventing intimal
      hyperplasia. The purpose of this study was to determine the dose and timing of
      Photofrin porfimer sodium needed to achieve a 3:1 or higher ratio between injured
      and control arteries after balloon endothelial injury. New Zealand White rabbits
      were anesthetized and their right femoral artery surgically exposed. A 4Fr
      Fogarty balloon catheter was passed retrograde into the lower abdominal aorta,
      inflated and pulled distally into the external iliac artery six times. All
      rabbits received heparin 100 IU/kg. Arteriotomies were closed and the animals
      recovered. Rabbits (n = 5 per group) were given intravenous Photofrin at a dose
      and time according to the following scheme: group I, 5.0 mg/kg immediately after
      balloon injury; group II, 2.5 mg/kg immediately after injury; group III, 5.0
      mg/kg after 1 week; group IV, 5.0 mg/kg after 2 weeks; or group V, 2.5 mg/kg
      after 2 weeks. Animals were killed 24h after drug administration and the
      aortoiliac segments removed for spectrophotofluorometric determination of
      Photofrin levels from injured and control segments. Mean(s.d.) ratios of injured:
      control arteries for groups I to V were 4.8 (2.6), 2.8 (1.2), 3.0 (1.0), 1.4
      (0.3) and 1.0 (0.0) respectively. This ratio was significantly higher for group I
      rabbits compared with groups IV and V (P < 0.01, ANOVA). Fluorescence and light
      microscopy showed that Photofrin was localized primarily in the tunica media, and
      that the drug must be administered before significant intimal hyperplasia
      occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574532
TI  - Primary aortoesophageal fistula caused by an atherosclerotic thoracoabdominal
      aortic aneurysm: a case report and review of the literature.
AB  - A 55-year-old woman suffered an episode of massive hematemesis caused by an
      aortoesophageal fistula from an atherosclerotic thoracoabdominal aortic aneurysm.
      In situ grafting of the thoracic portion of the aneurysm was followed by sepsis
      and a sinus tract between the mid-esophagus and the aortic prosthesis. Graft
      removal, aortic closure, esophageal closure and axillobifemoral bypass allowed
      clearing of the sepsis and recovery. Severe hypertension followed aortic closure
      and extra-anatomic bypass and resulted in the eventual death of the patient 16
      months later from dissection of the ascending aorta with pericardial tamponade.
      There are very few treated cases of aortoesophageal fistulas caused by
      atherosclerotic aneurysms reported in the literature. Furthermore, there are no
      reported cases where the aorta was closed at the level of the subclavian artery
      with extra-anatomic bypass to restore blood flow to the lower half of the body.

PMID- 8574533
TI  - Surgical management of concurrent, coeliac and bilateral iliac artery aneurysms.
AB  - A 76-year-old man was admitted with bilateral common iliac artery aneurysms found
      incidentally on computed tomography. Transfemoral digital subtraction
      arteriography demonstrated atherosclerotic plaques in the aorta with bilateral
      common iliac artery aneurysms and a coeliac axis aneurysm. The coeliac artery
      aneurysm was resected and an aortobifemoral bypass performed with reimplantation
      of the inferior mesenteric artery into the prosthesis. The patient was well when
      discharged 2 weeks after operation. The incidence, natural history and management
      of coeliac axis and iliac artery aneurysms are reviewed.

PMID- 8574534
TI  - Popliteal vein aneurysm.
AB  - The successful management of a popliteal vein aneurysm in a 25-year-old Saudi man
      is described. An extensive review of the English literature revealed another 11
      similar cases.

PMID- 8574535
TI  - Tracheoinnominate artery fistula following tracheostomy.
AB  - Tracheoinnominate artery fistula is a relatively rare but highly lethal
      complication occurring in patients with long-standing tracheostomies. Early
      evaluation of this problem and prompt aggressive therapy are necessary. When
      massive haemorrhage begins, immediate arterial compression, control of the airway
      and subsequent treatment of the injured artery may be lifesaving. Immediate
      surgical exploration through a median sternotomy is necessary to control the
      proximal and distal innominate artery. After the damaged artery has been excised,
      vascular reconstruction can be performed to preserve the connection between the
      proximal and distal ends of the innominate artery. A pedicled pericardial patch
      was successfully used for the tracheal reconstruction.

PMID- 8574536
TI  - Descending thoracic aorta aneurysmectomy: left-left centrifugal pump versus
      simple clamping technique.
AB  - Forty-six patients who had had an elective repair of a descending thoracic aortic
      aneurysm were reviewed, in order to investigate the efficacy of support by a
      centrifugal pump on distal organ perfusion and spinal cord protection during
      cross-clamping of the thoracic aorta. Two concurrent groups were analysed: 36
      patients (78%) were supported by left atriofemoral arterial bypass with a
      centrifugal pump and 10 (22%) had no distal circulatory support. No patient was
      fully heparinized. The demographic data and preoperative characteristics of the
      groups, including location and type of aneurysm, were similar. The mean(s.d.)
      duration of cross-clamping was 37.8 (16) min in the centrifugal pump group and
      42.3(21) min in the simple clamping group. Preoperative haemodynamic and
      laboratory data were similar in both groups. During cross-clamping, parameters of
      pH and blood urea varied but were better in the centrifugal pump group; changes
      from pre-intervention to early aortic cross-clamping time were not significant
      (pH, P < 0.0006; bases, P < 0.0003). Differences in creatinine values were caused
      mainly by the change from pre-intervention to the first postoperative day (P <
      0.03); this continued throughout the hospital stay. The cerebrospinal fluid
      pressure measurement indicated a significant difference in time change (P <
      0.0001) and mean level over time (P < 0.0002): levels were significantly lower in
      the centrifugal pump group throughout aortic cross-clamping. Three patients in
      the simple clamping group and none in the centrifugal pump group (P < 0.02)
      required cerebrospinal fluid drainage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574537
TI  - Normothermic versus hypothermic perfusion during primary coronary artery bypass
      grafting.
AB  - Normothermic versus hypothermic cardiopulmonary bypass was evaluated in 1442
      consecutive patients undergoing primary coronary artery bypass grafting (CABG).
      Group 1 (n = 545) were operated on in moderate systemic hypothermia (rectal
      temperature 28 degrees C) and group 2 (n = 897) in normothermia (rectal
      temperature 37 degrees C). Both groups had cold cardioplegic arrest (10 degrees
      C) and local cooling of the heart with slush. Anaesthesia and operative
      techniques were identical in both groups. The mean age was 60 years; group 2
      contained significantly more patients aged > 65 years (P < 0.05) and had more
      frequent emergency operations (P < 0.001) than group 1. Other preoperative
      patient characteristics were similar between groups. Aortic cross-clamping time
      was similar in both groups but cardiopulmonary bypass time was significantly
      longer in group 1 than in group 2 (97.9(28.8) versus 76.6(26.0) min, P < 0.001).
      Perioperative mortality rate was 3.3% in group 1 and 2.6% in group 2. The
      incidence of myocardial infarction was significantly higher in group 1 than in
      group 2 (2.0% versus 0.7%) Perioperative low cardiac output needing inotropic
      support was similar in both groups, but group 1 patients required more intra
      aortic balloon insertions (4.6% versus 2.2%, P < 0.05). Lower incidence of
      postoperative ventricular arrhythmias, shorter intubation time and less transient
      renal failures were significant in group 2 compared with those in group 1 (P <
      0.001), while re-exploration of bleeding, wound infections, pulmonary,
      neurological and gastrointestinal complications did not differ. Blood transfusion
      was less in group 2 (1.2(1.1) units, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574538
TI  - Arterial grafts for coronary artery surgery.
AB  - Fifty specimens of left internal mammary artery, right gastroepiploic artery and
      right inferior epigastric artery were examined for length, diameter and frequency
      of atherosclerotic changes. Mean usable length was 132.4 mm for internal mammary
      arteries, 127.9 mm for gastroepiploic arteries and 128.4 mm for inferior
      epigastric arteries. One gastroepiploic artery was occluded. Histological
      examination revealed atherosclerotic plaques in seven internal mammary arteries
      (14%), 12 gastroepiploic arteries (24%) and 14 inferior epigastric arteries
      (28%). These findings emphasize the superiority of the inferior epigastric artery
      as the graft of choice for coronary artery bypass grafting. Gastroepiploic artery
      and inferior epigastric artery should only be used as additional grafts if 'all
      arterial-grafting' is intended.

PMID- 8574539
TI  - Valve replacement for acute left heart endocarditis.
AB  - Between January 1982 and June 1993, 66 patients (48 men and 18 women of mean
      (range) age 50 (21-77) years) underwent valve replacement for acute infective
      endocarditis. There were 45 aortic valve and 17 mitral valve infections. Four
      patients had bivalvular involvement. Fifty-three patients suffered from native
      valve endocarditis, with underlying valvular lesions documented for 31 patients.
      Staphylococci and Streptococci spp. were responsible for 68% of infection, and
      20% of blood and valve cultures were negative. Refractory congestive heart
      failure was the leading surgical indication in 86% of patients. The mean follow
      up period was 44 months. The perioperative mortality rate was 6%. Actuarial
      survival rates were 88.5% at 1 year and 83% at 3 years. No early recurrence of
      infection was noted. Six patients (9%) needed reoperation. Satisfactory results
      confirm that early surgical management should be considered in patients with
      complicated infective endocarditis.

PMID- 8574540
TI  - Risk factors for early and late mortality in surgical treatment of coronary
      artery disease.
AB  - A total of 1025 patients who had coronary bypass surgery at the Surgical
      Department A, Rikshospitalet, Oslo, between 1982 and 1986, were analysed for
      factors associated with early mortality and long-term survival. The cumulative
      follow-up time accounted for 6553 patient-years; the median follow-up was 6.45
      years and ranged from the day of admission to 10 years. In total, 31 patients
      (3%) died within 30 days of surgery. Some 30 possible risk factors were analysed.
      Univariate analysis followed by a multivariate analysis defined six independent
      risk factors for early mortality. These were lack of sinus rhythm, previous heart
      surgery, mitral regurgitation, left main stem stenosis, unstable angina, and an
      elevated left ventricular end-diastolic pressure. Estimation of attributable risk
      showed that these factors could identify all patients who died early. Independent
      risk factors for late death were: lack of sinus rhythm, resection of a left
      ventricular aneurysm, left main stem stenosis, New York Heart Association (NYHA)
      class IV on admission, an elevated end-diastolic pressure, and prolonged cross
      clamping time. The attributable risk analysis showed that independent risk
      factors for total mortality explained only about half of the patients who died.
      This appeared to be because of the competing effect of non-cardiac mortality.
      Results of the study show that risk factors for early mortality are good
      indicators for the outcome of coronary artery bypass surgery, identifying all
      deaths, whereas long-term mortality cannot be predicted. Stratification of
      independent risk factors allows a better comparison of mortality in different
      centres, and also better quality control of bypass surgery.

PMID- 8574541
TI  - Epicardial electric shock ablation of the left lateral accessory pathway.
AB  - Fifty patients with drug-resistant, recurrent tachyarrhythmias causing Wolff
      Parkinson-White syndrome underwent surgery between 1990 and 1992. All recognized
      surgical methods for accessory pathway destruction were performed. Epicardial
      electric shock ablation was first used as a method of surgically destroying an
      accessory atrioventricular pathway in 1983. This technique avoids the need for
      cardioplegia and hypothermia during operation. The procedure is based on the
      application of a series of two to five electrical shocks (50-150 J) to the region
      of the atrioventricular groove where the accessory pathway has been previously
      located. Some 32 patients with a left free wall accessory pathway underwent this
      operation. Cardioplegia and hypothermia were not required in 22 patients with an
      accessory pathway located in the left lateral position. In the second group
      comprising ten patients with a left lateral accessory pathway, four were
      diagnosed as having a second pathway and four had concomitant heart pathology
      such as coronary artery disease -- one had an atrial septal defect and another
      had a ventricular septal defect. Accessory pathway ablation was carried out in
      these ten patients using epicardial electric shock under normothermic
      cardiopulmonary bypass. Concomitant heart pathology was corrected at the second
      stage of the operation under cardiopulmonary bypass with cardioplegia and
      hypothermia. Postoperative electrophysiological studies confirmed that the
      accessory pathway had been destroyed in all patients. The only side effects of
      epicardial electric shock application were transient ST elevation < 1 mm in four
      patients, transient atrioventricular bloc in two and moderate sinus tachycardia
      in three.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574542
TI  - Superior vena cava stenosis after orthotopic heart transplantation: complication
      of an alternative surgical technique.
AB  - Superior vena cava stenosis presented as a postoperative complication of
      orthotopic heart transplantation in a patient in whom a new surgical technique
      was used. This alternative technique consists of total excision of the
      recipient's atria, with donor heart implantation performed using bicaval and
      pulmonary venous anastomoses. This rare complication required surgical repair 1
      month after transplantation. The patient remains well on long-term follow-up. The
      pathogenesis, surgical management and modifications of the alternative technique
      to prevent this potentially serious complication are discussed.

PMID- 8574543
TI  - Papaverine injures the endothelium of the internal mammary artery.
AB  - Intraluminal injection of papaverine may be employed to dilate the internal
      mammary artery for use as a coronary artery bypass graft. The biochemical and
      morphological consequences of exposing the endothelium of the internal mammary
      artery to papaverine have been investigated. Biochemical injury was assessed by
      measuring changes in basal and vortex-stimulated prostaglandin I2 production, and
      morphological damage by scanning electron microscopy. Segments of internal
      mammary artery from 10 patients were placed in one of three solutions; papaverine
      (1.5 mg/ml of normal saline), normal saline acidified to the pH of the papaverine
      solution, and normal saline alone. Basal production of prostaglandin I2 was
      similar in the three groups but vortex-stimulated production was significantly
      lower in segments stored in papaverine (18.3 pg/mg) and acidified saline (19.1
      pg/mg) compared with that of saline alone (43.6 pg/mg). No consistent
      morphological difference was found by scanning electron microscopy. It was
      concluded that the low pH of the papaverine solution injured the endothelium of
      the internal mammary artery.

PMID- 8574544
TI  - Intracardiac pheochromocytoma with dual coronary blood supply: case report and
      literature review.
AB  - An intracardiac pheochromocytoma is extremely rare. This patient first presented
      postpartum at age 28 with clinical signs, symptoms and biochemical evidence
      suspicious for the diagnosis of pheochromocytoma. Multiple radiologic studies and
      laparotomy failed to confirm the diagnosis. Some 20 years later the patient
      presented with complaints of chest pain, palpitations, and flushing. Cardiac
      catheterization demonstrated a 'tumor blush' superior to the left atrium with a
      blood supply derived from the coronary arteries. Open-heart surgery was performed
      and the tumor successfully removed.

PMID- 8574545
TI  - Congenital aneurysm of the sinus of Valsalva dissecting into the interventricular
      septum.
AB  - The case of a 57-year-old man with a congenital aneurysm of the right sinus of
      Valsalva dissecting into the interventricular septum is presented. The patient
      had a previous heart block and aortic insufficiency. The diagnosis was made by
      echocardiography and cardiac catheterization. Open-heart surgery was performed,
      closing the entrance of the aneurysm and replacing the aortic valve. The patient
      survived surgery and is in New York Heart Association functional class II 3 years
      after surgical repair. Other cases of this uncommon congenital heart disease are
      reviewed.

PMID- 8574546
TI  - Easy and inexpensive diffusion tests for detecting the assimilation of aromatic
      compounds by yeast-like fungi. Part II. Assimilation of aromatic acids.
AB  - Since our assimilation diffusion tests were successful for dihydroxyphenols, the
      same procedure was used for development of assimilation of benzoic, salicylic and
      phenylacetic acids by selected yeast-like fungi. The acids were found to be well
      oxidized. Positive results may be obtained after 1-2 days of incubation.
      Consumption of the substances studied was very low, about 0.8 mg for one test.
      The diffusion tests were proposed to choose highly active strains from culture
      collections.

PMID- 8574547
TI  - Activities of cytochrome P450-dependent monooxygenases and antioxidant enzymes in
      different organs of Norway rats (Rattus norvegicus) inhabiting reference and
      contaminated sites.
AB  - Wild Norway rats (Rattus norvegicus) were collected from a site contaminated by a
      range of polycyclic aromatic hydrocarbons (PAHs), mineral oils,
      polychlorobiphenyls (PCBs) and heavy metals. Activities of cytochrome P450
      monooxygenases (ethoxy-, pentoxy- and benzoxy-resorufin O-dealkylases, and 4
      nitrophenol hydroxylase) were measured in microsomal fractions from liver and
      lung. Antioxidant enzyme activities (superoxide dismutase, catalase, selenium
      dependent and non-selenium-dependent glutathione peroxidases) were also measured
      in cytosolic fractions from lung and liver, and in erythrocytes. The levels of
      activities were compared with those found in control laboratory rats and in wild
      Norway rats reared in a terrarium. Results show that rats living in a polluted
      environment have monooxygenase activities higher than that of control animals in
      both liver and lung. Some modifications of antioxidant enzyme activities were
      also found in these animals.

PMID- 8574548
TI  - Determination of the aerobic biodegradability of polymeric material in a
      laboratory controlled composting test.
AB  - A laboratory method is presented for investigating the biodegradation of an
      organic test material in an aerobic composting system based on the evolution of
      carbon dioxide. In addition to carbon conversion, biodegradation can also be
      monitored through weight loss and physical disintegration. The test method is
      different from other biodegradation tests, especially aquatic tests, because of
      the elevated temperature representative for real composting conditions and also
      because of enhanced fungal degradation activities. A ring test was run using
      paper and poly-beta-hydroxybutyrate/valerate as test materials and cellulose
      powder as a reference material. The test results and the experience gained by the
      participants showed that the method is suitable and practicable. Experience with
      real technical-scale composting facilities confirms that the method provides test
      results of high predictive value. The test is designed to become a European
      Standard in connection with determining the compostability of packagings and
      packaging materials.

PMID- 8574549
TI  - Metabolism of the herbicide chlortoluron by human cytochrome P450 3A4.
AB  - Studies were carried out to investigate the metabolism of herbicide chlortoluron
      in the microsomal fractions and whole cells of Saccharomyces cerevisiae
      expressing human cytochrome P450 3A4. Both whole cells and microsomal fractions
      of yeast expressing human cytochrome P450 3A4 exhibited a typical dithionite
      reduced, CO-difference absorbance spectrum with maximum absorbance at 448 nm.
      Chlortoluron produced a type I binding spectrum with cytochrome P450 3A4 with a
      Ks value of 200 microM. Chlortoluron was metabolised into four metabolites;
      hydroxylated-N-monodemethylated, hydroxylated ring methylated, N-didemethylated
      and N-monodemethylated products. Chlortoluron metabolism was absolutely dependent
      on NADPH and no metabolism was observed in control transformants.

PMID- 8574550
TI  - Generator column determination of aqueous solubilities for non-ortho and mono
      ortho substituted polychlorinated biphenyls.
AB  - Aqueous solubilities of four non-ortho and eight mono-ortho substituted PCBs were
      determined using a generator-column technique followed by subsequent off-line
      GC/ECD analysis of the aqueous solutions. The method is based on pumping water
      through a column containing glass beads coated with the congener being studied
      and has been used to measure solubilities at room temperature. The method
      circumvents many of the experimental difficulties encountered with the
      traditional shake-flask system. Aqueous solubility of 3,3',4,4'
      tetrachlorobiphenyl determined by this procedure is compared with data obtained
      from the shake-flask method and the computational method. The precision of
      replicate measurements is better than +/- 6.5%. Aqueous solubilities determined
      for 12 congeners ranged from 6.07 x 10(-11) to 4.47 x 10(-9) mol/L and generally
      decreased with molecular weight and increased with degree of ortho-chlorine
      substitution within a molecular-weight class.

PMID- 8574551
TI  - A perspective on the role of surgery in chronic obstructive lung disease.
AB  - As can be judged by reading the description of these operations, much has been
      done throughout the twentieth century to try to improve the quality of life of
      emphysema patients. At the time of their description, all procedures were based
      on what appeared to be clear understanding of the pathogenesis of the disease,
      and all were championed by leading surgeons, mostly in Europe and in the United
      States. Early results were always encouraging, but the severity of emphysema and
      the wrong understanding of the problem were the limiting factors for sustained
      good results. In addition, clinical and functional results of surgery were
      difficult to assess because all reported series were small and inconsistent, and
      because no controlled trial was ever done to compare the results of standard
      medical therapy with that of surgery. It is also clear that the general failures
      of surgery to predictably improve dyspnea in emphysematous patients relates to
      the nonavailability of an experimental model in which physiologic parameters of
      success could be evaluated.

PMID- 8574552
TI  - Overview of the pathology of emphysema in humans.
AB  - In summary, emphysema in smokers should not be considered a single entity with
      predictable clinical and functional abnormalities. Decreases in flow are the
      ultimate abnormalities seen in COPD with emphysema; however, the pathophysiology
      of the flow alterations are vastly different in CLE and PLE. Based on the present
      understanding of emphysema, it could be predicted that the short-term results of
      pneumonectomy might produce some improvement in flows in CLE but not in PLE. Any
      improvement, however, may be short-lived, because the new mechanical conditions
      resulting from the removal of emphysematous lung would destroy the remaining lung
      at an accelerated rate, thus returning to the prior emphysematous state.

PMID- 8574553
TI  - Pathophysiology of chronic obstructive pulmonary disease.
AB  - Emphysema with bullae is a common feature of patients with chronic obstructive
      pulmonary disease. Central to the pathophysiology of emphysema is the presence of
      airflow obstruction and lung and chest hyperinflation. Because of the increased
      ventilatory demand and the need to maintain gas exchange, patients with emphysema
      increase their work of breathing. This article reviews the adaptive and
      maladaptive consequences of these changes. A rationale is given as to the
      possible mechanism by which surgery aimed at resecting hyperinflated portions of
      the lungs may be effective.

PMID- 8574554
TI  - Evaluation of the emphysematous patient.
AB  - Most of the patients with emphysema complain of dyspnea and become limited in
      their activities during the course of the disease. Dyspnea is probably due to the
      change in the configuration of the thorax which is secondary to hyperinflation.
      The investigation should include the radiologic quantification of the structural
      abnormalities of the lungs and the functional consequences of these changes. When
      volume reduction of the lung is considered, the effects of hyperinflation on the
      mechanic of breathing and the ventilatory response to exercise has to be
      investigated rigorously.

PMID- 8574555
TI  - Quality of life and predictions of survival in patients with advanced emphysema.
AB  - Although many factors have been shown to relate to survival in patients with
      emphysema and COPD, age and baseline post-bronchodilator FEV1 are the best
      predictors of mortality. It is important to note that mortality in patients
      presenting with a baseline FEV1 of 50% or greater is only slightly greater than
      in a group of healthy smokers. Moreover, the wide variability in survival in
      patients with severe airflow obstruction should cause clinicians to be cautious
      when attempting to estimate and discuss prognosis with patients.

PMID- 8574556
TI  - Medical management of emphysema.
AB  - In summary, this article attempted to provide a framework for the elaboration of
      a stepcare medical management plan for patients with COPD. An algorithm
      describing this approach is presented in Figure 1. Inhaled ipratropium bromide
      and beta 2-agonist are both effective bronchodilators and may be sufficient in
      mild disease. For patients with persisting limitation in daily activities,
      various combinations of beta 2-agonist, ipratropium bromide, and theophylline may
      be used to potentiate the efficacy of the treatment. If this proves insufficient,
      a trial of oral corticosteroids can then be instituted. Only those individuals
      with a reduction in airflow obstruction after this therapy are candidates to
      receive either low-dose oral or low-dose inhaled corticosteroids in order to
      maintain the improvement. Inhaled corticosteroids are of no clinical benefit to
      patients with advanced COPD unresponsive to oral corticosteroids. Arterial blood
      gas should be analyzed in patients with a FEV1 less than 50% of predicted value
      and oxygen therapy prescribed according to the prescription guidelines. Pulmonary
      rehabilitation is indicated in patients with reduced functional status, despite
      adequate drug treatment.

PMID- 8574558
TI  - Classification of cystic and bullous lung disease.
AB  - Cystic and bullous diseases of the lung are of special interest, referring to a
      wide variety of pathologic conditions. A thorough knowledge of these conditions
      and associated pathophysiology is necessary in planning the best type of
      treatment.

PMID- 8574557
TI  - Experimental emphysema.
AB  - This animal model of emphysema exhibits the same abnormalities in respiratory
      mechanics as those seen in human emphysema. The histologic and radiographic
      findings also closely resemble changes of panacinar disease. Moreover, the
      progressive hypoxemia preceding hypercarbia also parallels the clinical course
      seen in human disease. Drawbacks of this model include the long time period
      required to develop significant changes and the cost of maintaining the animals
      for such a time period. Large cystic areas were not noted in our animals and one
      would have to turn to another model to address the problem of giant bullous
      emphysema. There is no ideal animal model of pulmonary emphysema, and the
      usefulness of an experimental model should be judged on how well it answers the
      specific questions. Significant information has been obtained using various
      animal models of emphysema in lung transplantation, diaphragmatic function,
      pulmonary hemodynamics, and in several other areas. The dog appears to be a
      suitable model for thoracic surgical research on emphysema.

PMID- 8574559
TI  - Indications for surgery and patient work-up for bullectomy.
AB  - Bullectomy can be associated with significant improvement in dyspnea as long as
      patients are appropriately selected. This selection process begins with clinical
      history and determination of the size and location of the bulla. If a patient has
      a smaller bulla, which is less than 30% of the volume of the hemithorax, the
      dyspnea is unlikely to be related to the bulla and its excision is probably not
      indicated. Laros et al determined that for successful bullectomy, the bulla must
      occupy at least 50% of the hemithorax and show definite displacement of adjacent
      lung tissue. In addition, there must be no vanishing lung syndrome nor chronic
      purulent bronchitis. Wesley et al added that there should be radiologic evidence
      of compressed lung tissue that can be re-expanded by removal of the bulla, and
      that there should be evidence of regional imbalance with poor perfusion on the
      side of the bulla and relatively good perfusion on the contralateral side.

PMID- 8574560
TI  - Operative technique of bullectomy.
AB  - The exact indications and long-term results of surgical bullectomy are still not
      completely clear. Patients with large-sized, compressive bullae with a normal or
      near-normal underlying lung parenchyma may benefit from surgical bullectomy (when
      carefully performed) because it relieves symptoms of dyspnea and improves
      exercise tolerance. By contrast, the value of surgical bullectomy in patients
      with diffuse, noncompressive bullous disease is less satisfactory and clear,
      although bilateral pneumectomy (volume reduction) has been proposed recently as
      an alternative to lung transplantation.

PMID- 8574561
TI  - Videothoracoscopic operations for bullous lung disease.
AB  - Recurrent primary spontaneous pneumothoraces can be treated easily by
      videothoracoscopic techniques. Although long-term follow-up is still lacking,
      VATS apical blebectomy and apical pleurectomy give excellent short-term results
      with recurrence rates below 1%. Because the technique is less invasive than open
      thoracotomy, it is also advantageous for the treatment of patients with
      pneumothoraces secondary to emphysema. Thoracoscopic treatment of diffuse
      emphysema remains investigational.

PMID- 8574562
TI  - Results of bullectomy.
AB  - Bullous emphysema patients with severe dyspnea or repeated pneumothorax who
      demonstrate compression or crowding of relatively normal underlying lung can
      benefit significantly from surgical intervention. As much of the normal lung
      should be preserved as possible by excision only of the bullae. Buttressing of
      the stapled bases of the bullae may minimize postoperative air leak, allowing
      even simultaneous bilateral operation. Further experience and follow-up of the
      thoracoscopic approach to bullectomy may establish it as the approach of choice
      rather than thoracotomy.

PMID- 8574563
TI  - The surgical treatment of emphysema. The Brompton approach.
AB  - The vast majority of patients suffering with emphysema cannot be helped by
      surgery. A fortunate minority, consisting of specific subsets of patients, can
      benefit, but to do so the surgeon must have a flexible approach and select the
      optimal procedure for each patient. There is no one operation that is ideal in
      all circumstances. A major exploratory thoracotomy remains the approach of choice
      in specific situations (1) when dealing with the rare patient who has a
      congenital air cyst in the context of otherwise normal lungs. Local excision
      usually is possible but lobectomy may be necessary; (2) when dealing with an
      infected bulla in which the situation can only be ascertained at operation, where
      adhesions may cause difficulty and drainage may prove inappropriate, and lung
      resection is necessitated; and (3) when operating for a pneumothorax in which the
      situation can only be assessed at operation, and control of air leak is mandatory
      by ligation, bullectomy, or intracavitary drainage. The future role of video
      assisted operations in this context must await the longer follow-up of larger
      series. In the elective management of patients with emphysema, those with a
      dominant bulla we continue to treat by intracavitary drainage. The Brompton
      technique offers a simple, safe, and effective therapeutic option in carefully
      selected patients. We believe the advantages to be threefold. Firstly, the use of
      CT scanning, important in patient selection, allows one to plan the incision so
      that a minithoracotomy can be performed, reducing the morbidity and mortality
      formerly associated with thoracotomy in patients with poor respiratory reserve.
      Secondly, the approach obviates the need to resect adjacent lung tissue, which in
      a generalized and progressive disease may be physiologically of disproportionate
      importance. Finally, pleurodesis allows any future recurrent bullae to be
      intubated and drained percutaneously under local anesthetic with minimal risk of
      pneumothorax. In those patients who have generalized emphysema without
      significant bullae, the role of volume-reduction surgery is being investigated.
      We await longer-term follow-up but fear that with wider application this major
      operation will accumulate significant mortality. Transplantation remains an
      option that must be limited to the youngest patients and those who are close to
      the terminal phase of their illness.

PMID- 8574564
TI  - Surgery for complications of chronic obstructive lung disease.
AB  - Chronic obstructive lung disease (COLD) is a clinical entity characterized by
      chronic airway obstruction that includes pulmonary emphysema and chronic
      bronchitis with airway obstruction. Although most complications are treated
      medically, there are a few cases in which medical treatment is not effective and
      surgical treatment is necessary. Most complications of COLD requiring surgical
      treatment are those associated with bullous emphysema, such as pneumothorax, lung
      carcinoma associated with bulla, and infection of bulla. In this article, the
      indications, practical aspects, and problems and risks of surgical treatment for
      complications of COLD are discussed.

PMID- 8574565
TI  - Lung-volume reduction surgery for severe emphysema.
AB  - The lung-volume reduction procedure is a palliative one, designed to relieve
      dyspnea, and improve the patient's ability to carry out routine activities of
      daily living without significant limitations. The rationale for this procedure
      and its development are discussed. In addition, patient selection, operative
      technique, postoperative care, results, and complications are considered.
      Ultimately, the value of lung-volume reduction surgery will be determined by the
      balance between the magnitude and duration of benefit achieved on the one hand
      versus the morbidity and mortality produced on the other.

PMID- 8574567
TI  - Lung transplantation for emphysema.
AB  - Lung transplantation is an established treatment option for patients with
      emphysema due to chronic obstructive pulmonary disease or alpha 1-antitrypsin
      deficiency. Operative mortality is low in experienced centers and functional
      results are acceptable. Morbidity associated with triple drug immunosuppression
      is significant. Constant annual death rates due to obliterative bronchiolitis and
      other complications result in a 50% 5-year survival; therefore, lung
      transplantation should only be offered to those ideal candidates who have no
      other treatment option.

PMID- 8574566
TI  - Unilateral thoracoscopic laser pneumoplasty of diffuse bullous emphysema.
AB  - The technical details of thoracoscopic laser pneumoplasty (TLP) by means of a
      contact neodymium:yttrium-aluminum-garnet (Nd:YAG) laser is described.
      Retrospective analysis of 769 unilateral TLPs indicated that the operative risk
      is acceptable (6% 3-months mortality rate), and significant subjective and
      objective improvement was achieved. Recurrent bullous emphysema is discussed. TLP
      is an effective treatment of advanced emphysema.

PMID- 8574568
TI  - Anesthesia for patients undergoing surgery for emphysema.
AB  - Whatever the technique used may be, the anesthesia for emphysematous patients is
      always a delicate one. With more and more anesthesiologists dedicated to the use
      of anesthesia for pulmonary surgery and who are applying the principles described
      in this article, many emphysematous patients, sometimes severely ill who
      otherwise would not be a candidate for usual anesthesia, may now profit from
      surgery for emphysema owing to the use of safe and efficacious anesthesia.

PMID- 8574569
TI  - Cancer predisposition. Ataxia-telangiectasia at the crossroads.
AB  - ATM, the gene product mutated in the cancer susceptibility syndrome ataxia
      telangiectasia, is related to proteins involved in DNA repair and cell-cycle
      control, perhaps explaining how ATM prevents carcinogenesis.

PMID- 8574570
TI  - Cell division. Bud-site selection is only skin deep.
AB  - Yeast cells that divide by budding place new buds in predetermined locations.
      Recent studies of the subcellular localization of the Bud3 protein help to
      explain how this occurs.

PMID- 8574571
TI  - Dyslexia. Reading between the laminae.
AB  - Reading is one of the most complex tasks in which vision is involved. Our
      understanding of the visual system is contributing to the analysis of dyslexia, a
      reading disorder which may reflect abnormal visual processes.

PMID- 8574572
TI  - Autoimmunity. The Fas track.

PMID- 8574573
TI  - Thermosensation. Some like it hot.
AB  - The ability of organisms to respond to fluctuating temperatures is ubiquitous but
      poorly understood. Recent studies of nematodes reveal specific sensory neurons
      and interneurons that mediate thermotaxis.

PMID- 8574574
TI  - Calcium signalling. Cracking ICRAC in the eye.
AB  - Capacitative Ca(2+) entry produces the very rapid light response in Drosophila
      photoreceptors; studies using this amenable system may help unravel the machinery
      and mechanisms that underlie this Ca(2+)-entry pathway.

PMID- 8574575
TI  - Huntington's disease. Their loss is our gain?
AB  - 'Knockout' mice have been developed that lack the Huntington's disease gene, in
      an effort to gain insight into the disorder and into the pathophysiological
      effects of tri-nucleotide repeat expansion.

PMID- 8574576
TI  - Chromatin. Nucleosome assembly during DNA replication.

PMID- 8574577
TI  - Neural development. Spinning skin into neurons.
AB  - Basic helix--loop--helix proteins are transcriptional regulations with important
      roles in myogenesis and neurogenesis. One such protein, NeuroD, has an impressive
      ability to promote ectopic neuronal differentiation in xenopus.

PMID- 8574578
TI  - Protein structure. Why have six-fold symmetry?
AB  - Why do proteins proteins that encircle DNA have six-fold symmetry? One important
      factor may be the economy in protein mass with which DNA can be encircled by six
      globular subunits arranged in a ring.

PMID- 8574579
TI  - Cell regulation. Innocent bystanders or chosen collaborators?
AB  - Cyclins and cyclin-dependent kinases turn out to hve diverse functions, not all
      directly concerned with the cell cycle; do they provide a link between cell-cycle
      control and other cellular processes?

PMID- 8574580
TI  - Ion channels. A physiological function for polyamines?

PMID- 8574581
TI  - Pattern formation. Gurken meets torpedo for the first time.
AB  - Intercellular communication between oocyte and follicle cells, mediated by the
      gurken-torpedo/DER signalling pathway, has a crucial role in determining both
      anterior-posterior and dorsal-ventral polarity in Drosophila.

PMID- 8574582
TI  - Molecular inactivation. Spatially and temporally defined molecular knockouts.
AB  - Most monoclonal antibodies do not functionally inactivate the antigen they
      recognize. This limitation can be overcome by localized chromophore-assisted
      laser inactivation (CALI) of specific antibody-linked proteins.

PMID- 8574583
TI  - S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting
      the transition of replication origins to a pre-replicative state.
AB  - BACKGROUND: DNA replication and mitosis are triggered by activation of kinase
      complexes, each made up of a cyclin and a cyclin-dependent kinase (Cdk). It had
      seemed possible that the association of Cdks with different classes of cyclins
      specifies whether S phase (replication) or M phase (mitosis) will occur. The
      recent finding that individual B-type cyclins (encoded by the genes CLB1-CLB6)
      can have functions in both processes in the budding yeast Saccharomyces
      cerevisiae casts doubt on this notion. RESULTS: S. cerevisiae strains lacking
      C1b1-C1b4 undergo DNA replication once but fail to enter mitosis. We have
      isolated mutations in two genes, SIM1 and SIM2 (SIM2 is identical to SEC72),
      which allow such cells to undergo an extra round of DNA replication without
      mitosis. The Clb5 kinase, which promotes S phase, remains active during the G2
      phase arrest of cells of the parental strain, but its activity declines rapidly
      in sim mutants. Increased expression of the CLB5 gene prevents re-replication.
      Thus, a cyclin B-kinase that promotes DNA replication in G1-phase cells can
      prevent re-replication in G2-phase cells. Inactivation of C1b kinases by
      expression of the specific C1b-Cdk1 inhibitor p40SIC1 is sufficient to induce a
      prereplicative state at origins of replication in cells blocked in G2/M phase by
      nocodazole. Re-activation of C1b-Cdk1 kinases induces a second round of DNA
      replication. CONCLUSIONS: We propose that S-phase-promoting cyclin B--Cdk
      complexes prevent re-replication during S, G2 and M phases by inhibiting the
      transition of replication origins to a pre-replicative state. This model can
      explain both why origins 'fire' only once per S phase and why S phase is
      dependent on completion of the preceding M phase.

PMID- 8574585
TI  - Chemoattractant-controlled accumulation of coronin at the leading edge of
      Dictyostelium cells monitored using a green fluorescent protein-coronin fusion
      protein.
AB  - BACKGROUND: The highly motile cells of Dictyostelium discoideum rapidly remodel
      their actin filament system when they change their direction of locomotion either
      spontaneously or in response to chemoattractant. Coronin is a cytoplasmic actin
      associated protein that accumulates at the coritcal sites of moving cells and
      contributes to the dynamics of the actin system. It is a member of the WD-repeat
      family of proteins and is known to interact with actin-myosin complexes. In
      coronin null mutants, cell locomotion is slowed down and cytokinesis is impaired.
      RESULTS: We have visualized the redistribution of coronin by fluorescence imaging
      of motile cells that have been transfected with an expression plasmid containing
      the coding sequence of coronin fused to the sequence encoding the green
      fluorescent protein (GFP). This coronin-GFP fusion protein (GFP). This coronin
      GFP fusion protein transiently accumulates in the front regions of growth-phase
      cells, reflecting the changing positions of leading edges and the competition
      between them. During the aggregation stage, local accumulation of coronin-GFP is
      biased by chemotactic orientation of the cells in gradients of cAMP. The
      impairment of cell motility in coronin null mutants shows that coronin has an
      important function at the front region of the cells. The mutant cells are
      distinguished by the formation of extended particle-free zones at their front
      regions, from where pseudopods often break out as blebs. Cytochalasin A reduces
      the size of these zones, indicating that actin filaments prevent entry of the
      particles. CONCLUSIONS: These data demonstrate that coronin is reversibly
      recruited from the cytoplasm and is incorporated into the actin network of a
      nascent leading edge, where it participates in the reorganization of the
      cytoskeleton. Monitoring the dynamics of protein assembly using GFP fusion
      proteins and fluorescence microscopy promises to be a generally applicable method
      for studying the dynamics of cytoskeletal proteins in moving and dividing cells.

PMID- 8574584
TI  - The nuclear envelope prevents reinitiation of replication by regulating the
      binding of MCM3 to chromatin in Xenopus egg extracts.
AB  - BACKGROUND: A complex of MCM proteins is implicated in ensuring that DNA
      replicates only once in each cell cycle, by 'replication licensing'. The nuclear
      membrane is also implicated in replication licensing, but the relationship
      between the MCM proteins and the nuclear membrane is unclear. Here, we
      investigate the relationship between XMCM3 (a component of the Xenopus MCM
      complex), nuclear envelope permeability and the initiation of DNA replication
      once per cell cycle. RESULTS: Our results show that the nuclear envelope does not
      prevent the entry of XMCM3 into the nucleus, but that it does prevent the binding
      of XMCM3 to chromatin. We have also identified another component of the Xenopus
      MCM complex as a homologue of the Schizosaccharomyces pombe protein Cdc21. XMCM3
      does not preferentially co-localize with sites of DNA replication. Instead, it is
      almost uniformly distributed on chromatin and is suddenly lost during
      replication. XMCM3 crosses intact nuclear membranes of G2-phase HeLa cells but
      cannot then bind to chromatin. Permeabilization of the nuclear envelope allows
      the binding of XMCM3 to G2-phase chromatin. We have therefore resolved
      replication licensing into two stages. The first requires the entry of a
      cytosolic 'loading factor' that is excluded by the nuclear membrane;
      subsequently, MCM3 can bind to chromatin in the presence or absence of a nuclear
      membrane, but only if the loading factor has gained access in the absence of the
      membrane. CONCLUSIONS: The Xenopus MCM complex contains homologues of yeast MCM2,
      MCM3, MCM5 and Cdc21 proteins. XMCM3 is displaced from chromatin during
      replication. The nuclear envelope allows entry of XMCM3 into the nucleus, but
      regulates its binding to chromatin; binding requires a loading factor which
      cannot cross the nuclear envelope. Based on these results we present a two-stage
      model for replication licensing.

PMID- 8574586
TI  - The retinal pigmented epithelium is required for development and maintenance of
      the mouse neural retina.
AB  - BACKGROUND: During development of the vertebrate eye, there is a series of
      reciprocal cellular interactions that determine the fate of the eye components.
      Although evidence from organ culture suggests that the retinal pigmented
      epithelium (RPE) organizes the laminar structure of the differentiated neural
      retina, no role has been identified for the RPE in early eye development, nor has
      the later function of RPE been demonstrated in vivo. RESULTS: To investigate the
      role of RPE cells in eye development, we generated transgenic mice that carry the
      attenuated diphtheria toxin-A gene; this transgene was driven by the promoter of
      the gene encoding the tyrosinase-related protein-1, which is specifically
      expressed in pigment cells. Depending on the expression level of the transgene,
      the retinal epithelium was ablated before or after its differentiation into a
      pigmented cell layer. We show that an early ablation (embryonic day E10-11)
      resulted in disorganization of the retinal layer, immediate arrest of eye growth
      and subsequent eye resorption. A later ablation (E11.5-12.5) allowed the eye to
      be maintained during embryogenesis, but the laminar structure of the retina
      became disrupted by the end of gestation, the vitreous failed to accumulate the
      adults were anophthalmic or severely microphthalmic. In some microphthalmic eyes,
      a number of RPE cells escaped ablation and formed patches of pigmented cells; the
      laminar structure of the retina was maintained immediately adjacent to such
      pigmented areas but disrupted elsewhere. In both cases--early or late ablation of
      the RPE--the retina appears to be the primary affected tissue. CONCLUSIONS: We
      conclude that presence of the RPE is required for the normal development of the
      eye in vivo. Its presence early in development is necessary for the correct
      morphogenesis of the neural retina. After the neural retina has started to
      differentiate, the RPE is still necessary, either directly or indirectly, to
      maintain the organization of the retinal lamina.

PMID- 8574587
TI  - The GTP-binding protein Rac does not couple PI 3-kinase to insulin-stimulated
      glucose transport in adipocytes.
AB  - BACKGROUND: In insulin-sensitive cells, such as adipocytes and skeletal muscle,
      the activation of phosphoinositide 3-kinase (PI 3-kinase) is thought to be
      critical in allowing insulin to stimulate both the uptake of glucose and the
      translocation of a specialized glucose transporter, GLUT4, to the plasma
      membrane. However, the downstream mediators that couple PI 3-kinase to GLUT4
      translocation are still not known. Recent studies have shown that the GTP-binding
      protein Rac mediates some of the biological effects of PI 3-kinase, and these
      findings have led to the suggestion that Rac may be a common mediator for a
      variety of responses mediated by PI 3-kinase. To determine whether Rac couples PI
      3-kinase to glucose uptake in adipocytes, we produced 3T3-L1 cells expressing
      either a constitutively active Rac1 (V12 Rac1, containing a valine residue at
      position 12) or a dominant-inhibitory Rac1 (N17 Rac1, containing an asparagine
      residue at position 17). RESULTS: The stable expression of both V12 Rac1 and N17
      Rac1 led to observable phenotypes in 3T3-L1 cells; expression of V12 Rac1
      resulted in constitutive formation of lamellipodia and constitutive activation of
      the cJun-N-terminal kinase (JNK), whereas expression of N17 Rac1 inhibited the
      insulin-stimulated formation of lamellipodia. However, neither basal glucose
      uptake nor insulin-stimulated glucose uptake was affected by the expression of
      either mutant Rac protein. In addition, expression of V12 Rac1 did not reverse
      the inhibition of insulin-stimulated glucose uptake caused by the PI 3-kinase
      inhibitor wortmannin. CONCLUSIONS: These findings provide direct evidence that PI
      3-kinase does not use Rac to couple the insulin receptor to glucose uptake in
      adipocytes. Furthermore, the finding that Rac does not mediate glucose uptake in
      response to insulin is consistent with the idea that PI 3-kinase couples to a
      variety of different effector molecules in cells, and suggests that some of the
      specificity in the biological responses elicited by PI 3-kinase may be mediated
      by the activation of different effector molecules.

PMID- 8574589
TI  - Suicide substrates reveal properties of the homology-dependent steps during
      integrative recombination of bacteriophage lambda.
AB  - BACKGROUND: A fundamental feature of bacteriophage lambda site-specific
      recombination is the strict requirement for a region of sequence identity between
      recombining DNA duplexes. It has been difficult to understand how the
      recombination machinery identifies and responds to nonhomologies as subtle as a
      single base-pair substitution, because the reaction intermediates are transient
      and there are likely to be several different homology-dependent steps. In order
      to understand better how the recombination machinery compares parental sequences,
      we have used the recently developed 'suicide substances'--DNA containing 5'
      bridging phosphorothioate linkages--to monitor the timing of homology-sensing
      relative to the strand cleavage reactions. RESULTS: The cleavage reactions for
      the two different strands of attB, the bacterial recombination locus for lambda
      integration, show very different degrees of dependence on homology with the
      partner locus, attP. Strand cleavage at the B binding site for Int recombinase is
      insensitive to homology. In contrast, cleavage at the B' binding site strongly
      depends on homology in the three base pairs adjacent to the B site. Strand
      cleavage at the B site is apparently required for the readout of this homology
      but, surprisingly, joining of the cleaved B site to a partner is not.
      CONCLUSIONS: Our finding that cleavage at the B site is insensitive to homology
      shows that effective synapsis between partners does not depend on sequence
      matching. Cleavage at the B' site provides the earliest positive signal for a
      homology-dependent switch in the lambda recombination machinery. Because this
      switch can occur in the absence of strand joining, the results argue against
      models that invoke strand ligation as the critical element of homology-sensing.
      Alternative mechanisms are presented that involve varieties of non-covalent
      strand swapping. A synthesis of the present results and other recent experiments
      highlights the importance of the disannealing of complementary strands and their
      reannealing to new partners, a process traditionally described as branch
      migration. The reversibility of branch migration and its bias away from
      mismatched combinations are proposed to be the major mechanisms of homology
      sensing during lambda integration.

PMID- 8574588
TI  - Rapid induction of a novel costimulatory activity on B cells by CD40 ligand.
AB  - BACKGROUND: T cells and B cells communicate by direct cell--cell interaction that
      is crucial to the functioning of the immune system. It is well established that
      the interaction between B-cell-expressed CD40 and T-cell-expressed CD40 ligand
      (CD40L) is critical for T-cell-dependent antibody responses, but the role of this
      interaction in T-cell responses is less clear. In this study, we have used mice
      with targeted mutations in the genes encoding CD40L or CD28 to investigate how
      the CD40-CD40L interaction induces on B cells a costimulatory activity that acts
      in addition to antigen to trigger T-cell growth. RESULTS: We show that T cells
      from Cd40L-deficient mice induce a substantially reduced costimulatory activity
      on B cells compared to wild-type T cells, particularly at early time points.
      Surprisingly, T cells, from CD40L-deficient mice induce similar levels of B7-1
      and B7-2 as do wild-type T cells. We further show that the CD40L-mediated
      induction of costimulatory activity precedes the induction of B7-1, B7-2 and the
      heat-stable antigen (HSA). CD4 T cells isolated from the CD28-deficient mice can
      receive costimulatory activity from CD40L-induced B cells, demonstrating that the
      induced molecules can costimulate T cells by a CD28-independent mechanism. We
      have generated a novel monoclonal antibody that inhibits the CD40L-induced
      costimulatory activity. Expression of the epitope detected by this monoclonal
      antibody correlates with the induction of the costimulatory activity, and the
      molecule recognized by the monoclonal antibody is a single chain of around 85
      kDa, distinct from B7-1, B7-2, ICAM-1, ICAM-2, ICAM-3, HSA CD5, integrin and 4
      1BB ligand. CONCLUSIONS: Our results demonstrate that CD40L is both necessary and
      sufficient for rapid, T-cell-mediated induction of costimulatory activity on B
      cells. This costimulatory activity is distinct from B7-1 and B7-2, and is
      independent of CD28.

PMID- 8574590
TI  - The role of medullary ischemia in acute renal failure.
AB  - The introduction of new techniques for the determination of renal parenchymal
      oxygenation and intrarenal microcirculation has elucidated some important aspects
      in the pathophysiology of acute renal failure (ARF). Data accumulated over the
      last decade with these techniques, together with improved morphologic evaluation
      of the kidney, indicate that medullary damage may play a pivotal role in various
      forms of acute and chronic renal hypoxic and toxic insults. The outer medulla
      functions normally under hypoxic conditions, as a result of limited regional
      oxygen supply and high oxygen consumption for urinary concentration. Outer
      medullary oxygenation is critically balanced by mechanisms designed to adjust
      oxygen demand and supply, and their insufficiency may lead to ARF with hypoxic
      medullary damage. In this article, we outline our current concept of the
      physiologic control of medullary oxygenation and review the clinical conditions
      that predispose to hypoxic medullary damage, including rhabdomyolysis,
      hypercalcemia, or the exposure to endotoxin, nonsteroidal anti-inflammatory
      drugs, radiologic contrast agents, cyclosporine, FK506, and amphothericin. We
      shall indicate a possible role for medullary oxygen insufficiency in clinical
      conditions known to predispose to ARF, such as preexisting renal disease,
      diabetes mellitus, hypertension, atherosclerosis, effective volume depletion,
      urinary obstruction, or aging, and suggest potential strategies to preserve
      medullary oxygenation and integrity.

PMID- 8574591
TI  - Sepsis or ischemia in experimental acute renal failure: what have we learned?
AB  - Acute renal failure (ARF) has been studied in experimental settings for many
      years and has led to many insights into the cell biology of renal injury. The
      development of more clinically relevant models of renal injury combining
      endotoxemia, hypoperfusion, and nephrotoxins has led to a new appreciation of the
      role of the immune system in the pathogenesis of ARF. Endotoxin produces profound
      declines in renal blood flow even when systemic pressures are preserved, and this
      effect appears to be mediated by systemically and locally generated vasoactive
      factors including cytokines, platelet-activating factor, endothelin, and
      adenosine. Activated neutrophils (PMN) contribute to injury through the
      generation of cytokines, production of oxidants, or interactions with renal
      endothelium. Specific inhibition of immune activation at various steps has been
      shown to ameliorate the course of experimental endotoxic and ischemic ARF.
      Inhibition of PMN adhesion to endothelial cells by monoclonal antibodies to
      binding proteins, and blockade of thromboxane or interleukin action with specific
      inhibitors have all been shown to improve renal outcome in experimental ARF.
      These studies demonstrate that immunologically activated mediators are important
      in the pathogenesis of ARF in sepsis. Strategies to reduce the levels or to block
      the binding of specific cytokines may hold promise for the treatment of ARF in
      the critically ill.

PMID- 8574592
TI  - Nitric oxide in the regulation of renal blood flow.
AB  - Nitric oxide (NO.) is a simple molecule, synthesized from the amino acid L
      arginine by a family of enzymes, NO. synthase (NOS). The L-arginine-NO. pathway
      plays a dominant role in the control of renal function under various physiologic
      and pathologic conditions. NO. is continuously released by the endothelium, and
      controls the tone of the glomerular afferent arteriole by modulating myogenic
      response and the action of various vasoconstrictors. On the other hand, NO.
      produced by the macula densa controls glomerular hemodynamics indirectly through
      tubuloglomerular feedback and renin release. It appears that NO. is also involved
      in medullary circulation and tubular function and, therefore, pressure
      natriuresis. Thus, the L-arginine-NO. pathway seems to play an important role in
      sodium hemostasis. Under certain pathologic conditions, NOS may be induced in the
      endothelial, vascular smooth muscle, mesangial, and tubular epithelial cells, and
      in macrophages, producing a large amount of NO., which may contribute to
      progression of renal disease. In acute renal failure, endogenous NO. seems to
      have a protective role against renal damage, as the inhibition of NOS aggravates
      renal dysfunction and histology. Although dietary L-arginine supplementation has
      been shown to protect against progression of renal damage, clarification of the
      exact role of NO. and the mechanism of L-arginine's beneficial effects must await
      further investigation. Finally, the recent development of targeting specific NOS
      isoforms or tissue may help clarify the role of the L-arginine-NO pathway in
      various physiologic and pathologic conditions, leading to the development of new
      therapeutic modalities.

PMID- 8574593
TI  - Natriuretic peptides and acute renal failure.
AB  - The characterization of a complex cerebrocardio-renal axis responsible for fluid
      and electrolyte homeostasis, with the isolation and identification of natriuretic
      peptides, has provided a potential therapeutic window into a condition associated
      with high morbidity and mortality in the ICU--acute renal failure (ARF). The
      potent natriuretic, diuretic, and renovascular actions of this family of peptides
      directly challenge the pathologic aberration in intrarenal hemodynamic and
      tubular function characterized by this condition. Unfortunately, human studies
      have not shown atrial natriuretic peptide to be the panacea as animal studies
      originally suggested. However, studies were clouded by the impact of
      polypharmacy, multisystem pathology, the timing of intervention, and the lack of
      any clear dose-response relationship for these peptides. Nonetheless, hormonal
      manipulation of physiologic aberration remains a potential therapeutic reality
      with ongoing isolation and understanding of new peptides, such as urodilatin,
      which may yet impact upon the treatment and outcome of ARF in the near future.

PMID- 8574594
TI  - Molecular and cell biology of acute renal failure: new therapeutic strategies.
AB  - Acute renal failure (ARF) commonly occurs in critically ill patients. Despite
      improved dialysis techniques and recent advances in intensive care medicine,
      mortality from this condition remains unacceptably high. Increased understanding
      of the factors that mediate cellular injury, such as adenosine triphosphate
      depletion, intracellular calcium accumulation, and generation of reactive
      oxygenation species, as well as those that mediate recovery, such as locally
      produced and systemically released growth factors, provide fresh insights that
      can be used to develop new strategies to limit renal damage after acute insults
      and speed the repair process. Exogenous administration of growth factors, adenine
      nucleotides, and thyroxine, each of which can facilitate recovery of experimental
      ARF, in addition to factors yet to be identified, is a potentially exciting new
      therapeutic strategy to improve survival of patients with this condition.

PMID- 8574595
TI  - Vasoactive drugs and the importance of renal perfusion pressure.
AB  - Despite the often multifactorial nature of renal insults in critically ill
      patients, inadequate renal blood flow (RBF) is common and frequently causes a
      reduction in the glomerular filtration rate (GFR). Renal autoregulation acts to
      maintain both the RBF and GFR constant across a broad range of renal perfusion
      pressure (RPP) levels; however, the lower limit of this range (approximately 80
      mm Hg for RBF, and 10-15 mm Hg higher for GFR) is often above the RPP achieved in
      critically ill patients. Furthermore, renal autoregulation is often lost,
      resulting in a linear pressure-flow relationship in the "at-risk" kidney.
      Consequently, maintenance of an adequate RPP level is needed to optimize RBF.
      While this may require the use of vasopressor catecholamines with their attendant
      risk of renal vasoconstriction and a reduction in RBF, both laboratory studies
      and clinical data suggest that such reactions rarely occur with intravenous
      infusions of these drugs, and that RBF and renal function usually improve when
      RPP is augmented during shock. Preliminary data, using nitric oxide (NO.)
      synthase inhibitors to augment blood pressure, showed a detrimental effect on
      renal perfusion, perhaps due to the central role of NO. in the normal
      vasoregulation of the kidney. Dopaminergic agonists have been commonly used as
      renal vasodilators; however, their actions are complex and include a proximal
      tubular diuretic effect, renal vasodilation, and systemic hemodynamic effects.
      Their specific action to increase RBF and GFR has not been demonstrated in
      clinically relevant studies and no prospective randomized study has shown a
      reduction in the incidence of renal impairment or acute renal failure.

PMID- 8574596
TI  - The histopathology of acute renal failure.
AB  - The morphologic and immunohistologic features in acute renal failure (ARF) are
      discussed in this article. The focus is on tubular epithelial cell injury, the
      central pathologic finding in the majority of cases of ARF. Tubular damage may be
      due to sublethal or lethal cell injury. Cell necrosis, including classic
      coagulative necrosis and apoptosis, manifestations of sublethal injury, and
      tubular cell exfoliation are described in detail. Pathologic findings in native
      kidneys are described.

PMID- 8574597
TI  - The immune system in uremia and during its treatment.
AB  - Infectious complications are frequent and often lethal in patients with uremia.
      Serious alterations in neutrophil function, e.g., phagocytosis, mononuclear cell
      activation, cytokine production, complement activation, T-cell function, and
      adhesion molecule expression, have been documented in uremic patients. Uremia per
      se is a cause of some of these derangements, but much evidence now exists that
      blood-membrane interaction during dialysis is responsible for many of these
      abnormalities. This is particularly true when bio-incompatible cellulose-based
      membranes are used. In many of these patients, newly described granulocyte
      inhibitory proteins (GIP) can be demonstrated. These two proteins, GIP I and II
      (28 kD and 9.5 kD, respectively, in molecular weight), block effective bacterial
      killing, chemotaxis, and oxygen metabolism. It appears that GIP I is a member of
      the lightchain family, and GIP II is the advanced glycosilation end product of
      beta 2-microglobulin. Another inhibitory protein, degranulation inhibitory
      protein (DIP), has been isolated. This protein is 14 kD in molecular weight, and
      is identical to the angioplastic factor angiogenin. DIP levels are significantly
      elevated in patients undergoing dialysis. Much still needs to be learned about
      the interactions of these inhibitory proteins with other soluble inflammatory
      mediators and, in particular, cytokines. It is clear, however, that profound
      derangements in immune function take place during uremia and dialytic therapy.
      Such derangements are likely to play an important role in determining the rate of
      recovery of renal function and the patient's ability to respond to septic
      insults. Further insights into the pathogenesis of uremic-dialytic immune
      dysfunction are already yielding improved patient management and decreased
      infection rates.

PMID- 8574598
TI  - Biocompatible intermittent hemodialysis.
AB  - Since intermittent hemodialysis was first used systemically during the Korean
      war, the mortality of acute renal failure (ARF) in critically ill patients has
      remained high ( > or 50%). The lack of improvement may be a result of better
      resuscitation techniques and intensive care management that allow more severely
      ill patients to survive long enough to develop ARF. The concept that those
      patients with ARF die with, but not of, renal failure was challenged recently by
      the results of three prospective randomized trials. Each tested the hypothesis
      that the course of ARF and the fate of critically ill patients may be affected
      adversely by bioincompatibility reactions due to the dialysis membrane used
      (activation of complement and neutrophils). Schiffl and colleagues were the first
      to publish a full report on the results of their investigation comparing
      bioincompatible cuprophane (CUP) and biocompatible acrylonitrile AN 69 (Hospal,
      Lyon, France) membranes in 52 patients with ARF following cardiovascular surgery.
      The AN 69 group had a lower death rate (38% vs. 65%, p = 0.052), a lower
      proportion of patients dying from Gram-negative sepsis (40% vs. 71%, p = 0.0162),
      and an improved recovery of renal function. A similar trial comparing the use of
      CUP with biocompatible polymethyl-methacrylate (PMMA) was performed in 72
      patients with medical categories of ARF. Again, the use of a biocompatible
      membrane resulted in an improved survival rate (57% vs. 37%, p = 0.11) and better
      recovery of renal function (62% vs. 37%, p = 0.04). Of the 20 patients in each
      group who initially had nonoliguric ARF, the survival rates were 80% with PMMA
      and 40% with CUP (p = 0.01). The preliminary results of another multicenter study
      including 121 patients dialyzed with either bioincompatible cellulosic membranes
      or PMMA or polysulfone membranes seem to confirm these findings. The management
      of critically ill patients is sophisticated and expensive. The use of
      biocompatible membranes adds little to the overall costs and appears to be
      justified.

PMID- 8574599
TI  - Azotemia control by extracorporeal therapy in patients with acute renal failure.
AB  - The mortality rate for patients with acute renal failure (ARF) requiring renal
      replacement therapy remains unacceptably high. The cause of death in these
      patients has been thought to relate primarily to the nature of the condition that
      precipitated renal failure. However, recent investigations challenge that notion
      and suggest that the characteristics of the renal replacement procedure itself
      may influence outcome. The major considerations for the clinician prescribing
      renal replacement therapy to the patient with ARF are the therapy mode, the type
      of membrane used, and the dose of delivered therapy. The first two considerations
      have been discussed extensively in the medical literature and are reviewed
      elsewhere in this issue. However, the determination of the amount of delivered
      therapy, although standard practice in patients with end-stage renal disease, has
      not been assessed routinely in patients with ARF. Furthermore, the influence on
      patient outcome of the level of azotemia control achieved by the delivered
      therapy is unknown. The purpose of this review is to provide some insight into
      quantifying the amount of renal replacement therapy delivered to patients with
      ARF treated with either continuous or intermittent therapies. The expected level
      of azotemia control that can be achieved with each of these therapies is
      discussed. We suggest that quantification of the amount of delivered therapy and
      the level of azotemia control are important variables to be obtained and
      evaluated in future investigations seeking to understand the high mortality rate
      of patients with ARF.

PMID- 8574600
TI  - The nutritional management of acute renal failure in the intensive care unit.
AB  - The nutritional support of patients with acute renal failure (ARF) in the ICU has
      undergone major changes. Nutritional therapy in these patients should not depend
      on the impairment of renal function but on the severity of multiple organ failure
      (MOF). There are no differences in general rules for the nutrition of the
      critically ill with or without ARF. Because ARF, per se, does not affect energy
      expenditure, energy requirements in these patients are the same as in other MOF
      patients. Thirty to 35 kcal/kg/day should be administered as carbohydrate and
      lipid solutions, and the serum concentration of glucose and triglycerides
      controlled. In contrast to patients with chronic renal failure, in ARF patients
      nitrogen administration of approximately 1.5 to 1.7 g amino acids/kg/day is
      necessary to diminish protein catabolism. No clinical data exist about the best
      composition of the administered amino acids, but a mixture of essential and
      nonessential amino acids seems sensible; the exclusive administration of
      essential amino acids is obsolete. New dialysis techniques such as continuous
      renal replacement therapy offer the opportunity to adapt nutrition to each
      individual patient's needs. Using these techniques, there is no reason to reduce
      nutrition because of fluid restriction, as is often necessary in intermittent
      hemodialysis.

PMID- 8574601
TI  - Achievements and new directions in continuous renal replacement therapies.
AB  - The evolution of renal replacement therapy has permitted the treatment of
      critically ill patients with acute renal failure. In intensive care settings,
      continuous renal replacement therapies have been shown to be better tolerated and
      clinically useful. Continuous hemofiltration is now performed with blood pumps
      and double-lumen venous catheters, thus avoiding the complications found in
      previous arteriovenous treatments. The use of countercurrent dialysate flow has
      overcome problems related to low treatment efficiency. High clearances can now be
      obtained during continuous hemodialysis or hemodiafiltration, and adequate blood
      purification can be achieved even in severely catabolic patients. New replacement
      solutions allow for a more effective correction of acidosis and electrolyte
      imbalances. Finally, newly designed machines permit continuous therapies while
      minimizing staff workload. Continuous therapies are today moving toward newer
      indications and applications. The ability to remove proinflammatory substances by
      filtration and/or adsorption has opened a series of potential indications. The
      concept that renal support and protection take place during hemofiltration
      suggests that very early use of this technique is desirable, even before the
      onset of oliguria or azotemia.

PMID- 8574602
TI  - The management of renal failure in patients at risk of cerebral edema/hypoxia.
AB  - Intermittent modes of renal replacement therapy have been shown to cause an
      increase in intracranial pressure in susceptible patients, including those with
      acute liver failure and cerebral edema from trauma or post neurosurgery. Such
      changes are due to the combination of adverse effects on cerebral oxygen delivery
      and/or cerebral perfusion pressure and the generation of an osmotic gradient
      between plasma and cerebral tissues. With continuous renal replacement therapy
      (CRRT) these cardiovascular and cerebrovascular changes are generally much
      reduced. Patients with hepatic failure and those postneurosurgery are at risk of
      fatal intracranial hemorrhage. A drawback of CRRT is the need for anticoagulation
      of the extracorporeal circuit. Epoprostenol appears to confer a reduced risk of
      hemorrhage without reducing circuit lifespan in these patients compared with the
      effects of standard and fractionated heparins. Lactate metabolism is often
      impaired in patients with severe liver failure and the use of lactate-buffered
      hemofiltration replacement dialysis fluids, even at the reduced rates used in
      CRRT, may result in hyperlactatemia and failure to correct acid-base deficits;
      therefore, "lactate-free" fluids are to be preferred. The introduction of CRRT in
      the management of patients with acute renal failure complicated by cerebral edema
      has been associated with greater patient stability and improved outcome.

PMID- 8574603
TI  - Continuous hemofiltration for the failing heart.
AB  - The effect of hemofiltration (HF) was studied in three different groups of
      patients with severe heart failure refractory to inotropic support. Group I
      consisted of 72 patients who were treated preoperatively with HF. In 1,350
      patients (group II) undergoing several kinds of open heart surgery, HF was
      performed during cardiopulmonary bypass. In a third group (520 patients), HF was
      used postcardiotomy cardiogenic shock. Hemodynamic, metabolic, and PO2
      measurements were obtained before, during, and after continuous HF. During 2 to
      24 hrs of continuous HF, an increase in mean arterial pressure left ventricular
      stroke work index, and total peripheral resistance, as well as a decrease in left
      atrial pressure, were seen in groups II and III. In group I, all hemodynamic
      variables improved significantly; afterload and preload decreased, reversing
      cardiac dysfunction and restoring renal function. Continuous HF eliminates
      cardiopulmonary toxic metabolites (partly responsible for multiorgan dysfunction)
      from the plasma of patients with severe cardiac failure. The preliminary results
      indicate that the early use of HF offers an effective treatment which prolongs
      life in acute and severe congestive heart failure.

PMID- 8574604
TI  - Continuous hemofiltration as blood purification in sepsis.
AB  - Continuous hemofiltration was first described as a new form of renal replacement
      for critically ill patients in the late 1970s. Since then, it has undergone
      remarkable technical and conceptual modifications and has become a widely used
      form of dialytic therapy in the ICU. More recent insights into the pathogenesis
      of sepsis and the role of soluble molecules in the mediation of organ injury
      during septic shock have led to a resurgence of the concept of blood purification
      during life-threatening infection. Recent studies have confirmed that cytokine
      extraction occurs in vivo in humans during continuous hemofiltration and that
      other smaller, potentially noxious molecules such as platelet-activating factor,
      complement factors C5a and C3a, and thromboxane are also removed from the
      circulation of septic patients or animals. Experimental studies have shown that
      continuous hemofiltration has beneficial hemodynamic effects in septic animals
      and that such effects may correlate with the intensity of ultrafiltration.
      Cardiac function also appears to improve and myocardial depressant factors are
      removed from the circulation. Continuous hemofiltration offers some promise as an
      adjunctive form of treatment in severe sepsis.

PMID- 8574605
TI  - Continuous hemofiltration: nursing perspectives in critical care.
AB  - Daily hemofiltration circuit management in Australian ICUs is a nursing activity
      predominantly utilizing venovenous access and a BMM 10-1 (Gambro, Lund, Sweden)
      blood pump. The design of the hemofiltration circuit should enable the easy
      addition of replacement fluids, the administration of anticoagulant drugs, and
      the collection of ultrafiltrate (UF). The ability to measure circuit pressures
      both before and after the filter may assist in the understanding of circuit
      dynamics and the prediction of filter dysfunction. Ultrafiltration (vol/hr) can
      be maximized using readily available intravenous pumps; however, the limitations
      of this (i.e., volume accuracy) need to be considered. The day-to-day nursing
      management of patients undergoing continuous venovenous hemofiltration (CVVH)
      requires continuous assessment and monitoring to prevent complications associated
      with fluid/electrolyte imbalance, blood and heat loss, infection, poor UF
      production, and foreign substance reaction. We have found that the nursing staff,
      therefore, requires a variety of educational strategies to gain expertise and,
      thus, provide a high standard of nursing management for this therapy. Quality
      assurance is also a necessary adjunct to the safe and efficient use of CVVH.

PMID- 8574606
TI  - Drug administration in critically ill patients with acute renal failure.
AB  - Patients with acute renal failure are commonly treated by continuous renal
      replacement therapies. To understand drug disposition in multiple organ failure
      patients, the pharmacokinetics of 18 drugs were evaluated in 243 patients.
      Continuous hemofiltration served as a model for constant elimination rates. In
      addition, the elimination of drugs was investigated during extracorporeal lung
      support. The dosage of 11 of 15 drugs had to be reduced as a result of these
      kinetic studies. Wide variability in volumes of distribution, clearances, and the
      extrarenal fractions of elimination were detected. There was a close correlation
      of the latter with Acute Physiology and Chronic Health Evaluation II scores of
      illness severity. A new algorithm was developed for primary estimates of drug
      dosage during hemofiltration and other organ support systems. Two in vitro
      studies confirmed the clinical results on drug sieving and provided important
      information on adsorption to membranes. A clinical validation study of the
      algorithm improved drug dosage. A simplified therapeutic drug monitoring approach
      is given.

PMID- 8574607
TI  - Acute renal replacement in the intensive care unit: now and tomorrow.
AB  - Although acute renal failure (ARF) requiring dialysis affects only approximately
      4% to 7% of patients admitted to the ICU, such individuals tend to be the sickest
      and most challenging patients in the ICU. The presence of ARF dramatically
      complicates their care and mandates the use of extracorporeal renal replacement
      therapy (RRT). The use of such therapy, with its technical and physiological
      demands, further complicates treatment. Not surprisingly, therefore, several
      controversies surround the management of these patients: the techniques of RRT,
      the indications and timing for their application, the intensity of their use, the
      selection of suitable patients, the nature of appropriate monitoring and
      physiologic targets for their application, the type of specialist best suited for
      the daily management of such patients, the cost-effectiveness of RRT, and the
      expansion of its use to treat patients without ARF. In many ways, the response to
      these controversies has diverged between Europe, Australia, and New Zealand on
      the one hand, and the United States on the other. In this article, we illustrate
      these sometimes quite different philosophies by presenting two perspectives (from
      Australia and the United States) on a number of important issues pertaining to
      RRT.

PMID- 8574608
TI  - The facts about methotrexate in rheumatoid arthritis.

PMID- 8574609
TI  - HLA-B27 and spondylarthropathies: the plot thickens.

PMID- 8574610
TI  - Pancytopenia and severe cytopenia induced by low-dose methotrexate. Eight case
      reports and a review of one hundred cases from the literature (with twenty-four
      deaths)
AB  - Severe adverse effects of low-dose methotrexate (less than 20 mg per week) are
      believed to be rare. We report eight cases of severe tricytopenia or pancytopenia
      seen in two medical departments of the same hospital in patients receiving low
      dose methotrexate. Three patients had been under methotrexate for less than one
      month. Of the six patients with joint disease, five had rheumatoid arthritis and
      one psoriatic arthritis. A review of the literature found 92 previously reported
      cases of severe tricytopenia or pancytopenia induced by low-dose methotrexate. Of
      the total of 100 cases, 24 were fatal and 25 occurred within one month of
      treatment initiation. Potential risk factors were identifiable retrospectively in
      at least 50% of cases but were not all predictable or present at treatment
      initiation. In 30% of cases, no explanation for the hematologic complication was
      found, and in an additional 20% missing data precluded definite conclusions. The
      role of the risk factors incriminated in the literature is discussed. Although
      infrequent, cytopenia is a severe complication of methotrexate therapy that
      warrants a number of precautions, including periodic creatinine clearance and
      serum albumin determinations. Furthermore, the weekly dosing schedule should be
      printed on methotrexate boxes.

PMID- 8574611
TI  - The HLA B27 antigen-spondylarthropathy association. Impact on clinical
      expression.
AB  - To determine the impact of the HLA B27 antigen on the expression of
      spondylarthropathies, we conducted a retrospective cross-sectional study of the
      116 spondylarthropathy patients whose HLA B27 phenotype was determined during a
      stay in the Morvan Hospital rheumatology department, Brest, France, between
      January 1, 1986, and December 31, 1994. Age at disease onset was younger in the
      HLA B27-positive patients (31.5 +/- 14 years versus 40 +/- 15 years; p = 0.008),
      who were more likely to have buttock pain (odds ratio, 4.84; p < 0.001) and
      roentgenographic evidence of sacroiliitis (odds ratio, 5.34; p < 0.001) and less
      likely to have psoriasis (odds ratio, 0.15; p < 0.0001), as compared with their
      HLA B27-negative counterparts. Peripheral arthritis occurred in similar
      proportions of patients with and without the HLA B27 antigen. Presence of HLA B27
      was of little value for the diagnosis of spondylarthropathy in patients with
      inflammatory joint disease involving peripheral joints (sensitivity 50%,
      specificity 92%, positive predictive value 53%, negative predictive value 91%).
      Higher mean values of the erythrocyte sedimentation rate (40.3 versus 30.6 mm/h;
      p < 0.05) and serum C-reactive protein level (29.8 versus 16.8 mg/L, p < 0.005)
      were seen in patients with the HLA B27 antigen. Our data from patients with any
      form of spondylarthropathy show that the HLA B27 antigen is associated with
      earlier-onset disease, involvement of the sacroiliac joints and more severe
      inflammation.

PMID- 8574612
TI  - Tubular excretion of phosphate in Paget's disease of bone. Effect of pamidronate.
AB  - Two recent reports of phosphate diabetes in pagetic patients prompted us to
      evaluate urinary phosphate and its variations under pamidronate therapy in
      Paget's disease of bone. We also investigated whether Paget's disease is
      associated with phosphate diabetes. Urinary phosphate excretion was determined in
      75 pagetic patients with a mean age of 72 years. None of the patients had
      received treatment during the six months preceding the evaluation. The 30
      patients with clinical, laboratory test, and/or roentgenographic evidence of
      active Paget's disease were given intravenous pamidronate in a dosage of 60 or
      120 mg. The control group was composed of thirty-seven age- and sex-matched
      subjects selected among patients admitted for degenerative bone or joint
      diseases. Phosphate and calcium levels were determined in blood and urine on two
      consecutive days in both cases and controls. The same assays were repeated six
      months after pamidronate therapy in the 30 patients with active Paget's disease.
      Phosphate diabetes was defined as a phosphate clearance above 20 ml/mn, a rate
      for tubular reabsorption of phosphate above 80%, and a ratio of the maximal rate
      for tubular reabsorption of phosphorus over the glomerular filtration rate
      (TmP04/GFR) below 0.80 mmol/l. As compared with controls, untreated cases had a
      nonsignificant increase in phosphate clearance (16.78 +/- 10.40 ml/mn versus
      14.81 +/- 7.20 ml/mn), a significant decrease in tubular reabsorption of
      phosphate (83.41 +/- 5.57% versus 86.70 +/- 5.30%; p < 0.05), and a
      nonsignificant decrease in the TmP04/GFR ratio (0.93 +/- 0.14 mmol/l versus 0.98
      +/- 0.15 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574614
TI  - Impact of using stored cells for immunofluorescence detection of antiperinuclear
      factor on sensitivity of the method for the diagnosis of rheumatoid arthritis.
AB  - Antiperinuclear factor is as sensitive as (0.75 to 0.80) and more specific than
      (0.94 to 0.97) rheumatoid factor for the diagnosis of rheumatoid arthritis.
      Although three groups found similar performance characteristics using the assay
      technique described by Youinou, lower sensitivities have also been reported. To
      clarify these discrepancies, we investigated each parameter of the assay,
      including storage time of the oral mucosa cells used as the substrate. Even when
      the slides were frozen, titers fell by one dilution within the first week and by
      two dilutions within two weeks after sampling. This decline seemed related to
      storage rather than to freezing: slides kept at 4 degrees C yielded an apparent
      three-dilution fall in titers after one week and were unevaluable after longer
      storage times. Successive freeze-thaw cycles did not influence results when the
      assay was done on the day the cells were sampled and fixed. Titers in sera stored
      at -25 degrees C remained unchanged or decreased by no more than one dilution
      during the first 18 months but declined thereafter. These data emphasize the need
      for performing the assay on the same day or, at the latest, on the day after
      fixation of the slides. That this precaution was taken should be specified in the
      "Methods" section of articles on antiperinuclear factor detection.

PMID- 8574613
TI  - Osteitis condensans of the clavicle: does fibrocartilage play a role? A report of
      two cases with spontaneous clinical and roentgenographic resolution.
AB  - Two cases of osteitis condensans of the medial clavicle with an unusual course
      toward spontaneous resolution of clinical and roentgenographic manifestations are
      reported. The relevant literature is reviewed. A pathogenic hypothesis for
      condensing osteitis of the clavicle, ilium, and pubis is suggested. At all these
      sites, the sclerosis occurs in bone overlaid by fibrocartilage. In contrast,
      joint aspects spared by the sclerosis are covered with hyaline cartilage. We
      report data documenting this fact at the sternoclavicular joint.

PMID- 8574615
TI  - The history of rheumatoid factor.
AB  - The events that led to identification of rheumatoid factor are narrated, and the
      respective contributions of the researchers who worked to achieve this goal are
      clarified. Changes that have occurred over time in concepts concerning the
      clinical significance and pathophysiologic role of rheumatoid factor are briefly
      summarized.

PMID- 8574616
TI  - Autoimmunity. Insights provided by the SCID mouse model.
AB  - CB17 SCID mice have severe combined immunodeficiency as a result of a mutation on
      chromosome 16 responsible for deficient activity of an enzyme involved in DNA
      repair. Because VDJ rearrangement does not occur, the humoral and cellular immune
      systems fail to mature. SCID mice do not reject human cells. They have been used
      to study the development of human tumors, human hematopoiesis and humoral
      responses in antibody-dependent organ-specific autoimmune diseases and in
      systemic lupus erythematosus. Studies involving grafting of synovial membrane
      under the renal capsule or in the subcutaneous tissue of SCID mice have provided
      information on the cells involved in the pathogenesis of rheumatoid arthritis.
      SCID mice have also been used to study adhesion molecules that play a role in the
      recruitment of lymphocytes in rheumatoid synovial tissue. The SCID mouse model
      provides new means of investigating immunologic treatments for rheumatoid
      arthritis.

PMID- 8574617
TI  - Sciatica as the first manifestation of synovial sarcoma. Contribution of magnetic
      resonance imaging to the diagnosis.
AB  - A 38-year-old man presented with paralyzing sciatica as the first manifestation
      of synovial sarcoma of his right leg. Although neurologic symptoms sometimes
      occur as manifestations of synovial sarcoma, they are exceptionally inaugural.
      Magnetic resonance imaging is a valuable tool in patients with synovial tumors,
      both for establishing the diagnosis and for evaluating the extent of the lesion.

PMID- 8574618
TI  - Osteomalacia as a presenting manifestation of Sjogren's syndrome.
AB  - Osteomalacia is still common in Morocco, where the leading causes are nutritional
      deficiencies followed by intestinal diseases. Osteomalacia rarely occurs as the
      first manifestation of a renal tubule disorder due to a connective tissue disease
      such as Sjogren's syndrome. The case of a 40-year-old woman who presented with a
      five-year history of generalized bone pain, severe weight loss and a waddling
      gait is reported. She had low levels of serum phosphate (0.74 mmol/L), serum
      calcium (1.97 mmol/L), and urinary calcium (1.22 mmol/24 h). Serum alkaline
      phosphatase was 210 IU/L. Roentgenograms showed Looser's zones (right femoral
      neck, sixth and seventh right ribs). There was bilateral parotid gland
      enlargement, dryness of the mouth, nose and eyes, and bilateral punctate
      keratitis. A lip biopsy showed changes corresponding to stage II of the Chisholm
      and Mason classification. Tests for rheumatoid factor (latex and Waaler-Rose) and
      antinuclear factor were negative. The alkaline reserve was 18 mmol/L, serum
      potassium was 3.5 mmol/L, serum chloride was 112 mmol/L and urinary pH was 6.5. A
      renal biopsy showed tubulointerstitial lesions, lymphoplasmocytic infiltrates and
      interstitial sclerosis with patchy tubular atrophy. The patient was given
      bicarbonates, high-dose vitamin D followed by 1-alpha-hydroxycholecalciferol (0.3
      microgram/d), and calcium (1 g/d). Follow-up was 42 months at the time of this
      writing. The role of tubular disorders in the genesis of osteomalacia is
      discussed, and the renal manifestations of Sjogren's syndrome are reviewed.

PMID- 8574619
TI  - No evidence of lumbar osteopenia in young adults with recent onset of reflex
      sympathetic dystrophy syndrome of the limbs. A single-energy computed tomography
      study (preliminary results)

PMID- 8574620
TI  - Intraneural myxoid cyst of the common peroneal nerve. A rare cause of sciatic
      paralysis.

PMID- 8574621
TI  - Acute ischemia of an upper limb as the first manifestation of hydroxyapatite
      crystal deposition disease.

PMID- 8574622
TI  - Butterfly vertebra: look for Alagille's syndrome.

PMID- 8574623
TI  - The quest for the ideal therapy for giant cell arteritis.

PMID- 8574624
TI  - Autoantibodies to cytokines in inflammatory joint disorders.

PMID- 8574625
TI  - Should we define osteoporosis based on bone mineral density criteria?

PMID- 8574626
TI  - A study of ovarian function in rheumatoid arthritis.
AB  - Ovarian function was evaluated prospectively in 16 female rheumatoid arthritis
      patients in the childbearing age. None of the patients was using oral
      contraceptives. The control group included 31 women with tubal sterility. Serum
      levels of estrone, 17 beta-estradiol and progesterone were assayed and used to
      determine an estrogen index and a luteal index. An ovulatory score was calculated
      as the sum of the estrogen and luteal indices. Estrogen levels were lower in the
      rheumatoid arthritis group than in the control group, but the difference was not
      significant. No statistically significant difference was found for progesterone
      levels, suggesting that luteal function was normal in the rheumatoid arthritis
      patients. The rheumatoid arthritis group had a significantly lower mean ovulatory
      score reflecting a decreased likelihood of ovulation as compared with the control
      group (p < 0.01). This abnormality may explain why fertility is reduced in women
      with rheumatoid arthritis.

PMID- 8574627
TI  - Arthrography and computed arthrotomography study of seventy patients with primary
      glenohumeral osteoarthritis.
AB  - Seventy patients with primary glenohumeral osteoarthritis underwent
      roentgenographic and computed tomography studies. Glenohumeral joint space loss
      and a normal acromiohumeral space were the roentgenographic inclusion criteria.
      Women made up 61% of the sample. The dominant shoulder was affected in 95% of
      cases and both shoulders in 41%. Mean age at first evaluation was 65 years.
      Arthrography showed a tear confined to the supraspinatus tendon in 16 cases
      (23%); no patients had tears involving more than one tendon. Computed tomography
      demonstrated glenoid retroversion (mean 16 degrees) but was unable to
      differentiate primary glenoid dysplasia from wear due to osteoarthritis.
      Posterior subluxation of the humeral head was found in 28 cases (40%) but was not
      consistently correlated with the presence of glenoid retroversion.

PMID- 8574628
TI  - Predictors of the need for total hip replacement in patients with osteoarthritis
      of the hip.
AB  - RATIONALE: the natural history and risk factors for hip osteoarthritis are still
      unknown. OBJECTIVE: to identify factors predicting a need for total hip
      replacement at some time during the course of hip osteoarthritis. PATIENTS AND
      METHODS: outpatients evaluated between 1981 and 1986 for hip osteoarthritis were
      studied retrospectively. The date of diagnosis and the characteristics of the
      patients and hip disease at diagnosis were recorded. The risk of eventual total
      hip replacement was estimated using the Kaplan-Meier method. Uni- and
      multivariate Cox proportional hazard models were used to determine the value of
      each variable for predicting total hip replacement. RESULTS: we included 149
      patients (50 males). The risk of total hip replacement was estimated at 36 +/- 4%
      five years after diagnosis. Factors with significant effects in the multivariate
      analysis were age older than 54 years at diagnosis (relative risk 3.15), body
      mass index greater than 27 (relative risk 2.97), and severe radiological joint
      space narrowing at diagnosis (relative risk 2.26). CONCLUSION: this study
      confirmed the often severe course of hip osteoarthritis and identified several
      factors possibly associated with rapid progression.

PMID- 8574629
TI  - Current prevalence of Paget's disease of bone in a region of France (Anjou).
AB  - To study the prevalence of Paget's disease in a region of France (Anjou) we
      conducted a two-part study. 1) One hundred randomly selected medical records of
      Paget's disease patients managed in a rheumatology department were studied to
      determine the rates of occurrence of pagetic lesions at each skeletal site.
      Availability of a radionuclide bone scan done before treatment initiation and of
      radiographs of hyperactive areas was required for inclusion into the study. In
      91% of patients, pagetic lesions were visible on the lumbar spine-pelvis-femoral
      head film. 2) We looked for pagetic lesions on intravenous urograms done in 600
      urology department patients (to minimize recruitment bias). The 307 males and 293
      females had a mean age of 65.4 +/- 8.7 years (range 50-91). Films classified by
      the evaluator as showing definite or doubtful pagetic lesions were read by five
      other evaluators in a blind manner. Among the 11 patients (seven males and four
      females) found to have Paget's disease, only one was younger than 65 years.
      Prevalence was higher in males (2.50 +/- 0.79% than in females (1.50 +/- 0.5%).
      These prevalences are lower than those reported in the United Kingdom.

PMID- 8574630
TI  - Prevalence and biological consequences of vitamin D deficiency in elderly
      institutionalized subjects.
AB  - The prevalence of vitamin D deficiency was evaluated in a population of elderly
      institutionalized subjects in seven long-term geriatric care facilities in France
      (Amiens, Francheville, Ivry, Lille, Montpellier, Oissel and Villejuif). Residents
      whose functional capability was relatively good were entered into the study.
      There were 126 patients (99 females and 27 males) with a mean age +/- SD of 84 +/
      6.6 years. All subjects had been institutionalized for over six months and were
      capable of walking at least as far as the dining room. None had received vitamin
      D or other compounds known to affect the metabolism of phosphorus and calcium
      within six months before the study. Vitamin D status was evaluated by determining
      serum 25 hydroxyvitamin D (25 OH D) levels using a radiocompetition assay after
      extraction and chromatographic separation. Mean serum 25 OH D was 3.17 +/- 2.52
      ng/ml (median 2.5). Eighty-five per cent of subjects had serum 25 OH D values of
      less than 5 ng/ml and 98% had values under 10 ng/ml, which is the cutoff usually
      taken to define vitamin D deficiency. Mean serum levels of intact parathyroid
      hormone were increased approximately two-fold as compared with values in healthy
      adults (70 +/- 39 pg/ml versus 33 +/- 12 pg/ml). Biochemical markers for bone
      formation (alkaline phosphatase, osteocalcin) and bone resorption (TRAP,
      hydroxyproline, pyridinoline) were all increased, with mean values 1.4-fold to
      3.4-fold those seen in healthy adults. Serum 25 OH D levels were negatively
      correlated with serum intact parathyroid hormone levels (r = 0.41; p < 0.0001).
      Serum intact parathyroid hormone levels were positively correlated with alkaline
      phosphatase activity (r = 0.30; p < 0.001) and serum osteocalcin levels (r =
      0.36; p < 0.0001) and negatively correlated with corrected serum calcium levels
      (r = -0.20; p < 0.02). Conclusion. Our data demonstrate that severe vitamin D
      deficiency is present in virtually all elderly institutionalized subjects and is
      accompanied with secondary hyperparathyroidism responsible for increases in
      markers of bone remodeling. Routine vitamin D supplementation is warranted in
      elderly institutionalized subjects.

PMID- 8574631
TI  - Insufficiency fractures of the sacrum in elderly subjects.
AB  - Elderly patients who develop insufficiency fractures of the sacrum usually have
      generalized bone loss and/or lesions of the pelvic bones (due to radiation
      therapy or previous fractures). The sacral fracture occurs either spontaneously
      or after a trivial traumatic episode. We compared patients admitted for sacral
      fractures (n = 12) or vertebral crush fractures (n = 56) in an effort to identify
      risk factors for sacral fractures. We conducted a retrospective review of the
      medical records of the 12 patients older than 70 years who were admitted to the
      rheumatology department of the Morvan Hospital between January 1, 1985 and
      December 31, 1994 for evaluation of a sacral fracture. The onset of symptoms was
      abrupt in 11 patients and occurred after an unremarkable fall in three. Patients
      admitted for sacral fractures were significantly more likely to have a positive
      history for a fracture, femoral surgery, or pelvic radiation therapy than
      patients admitted for vertebral fractures (58% versus 9%, p = 0.0005). In
      contrast, levels of calcium, phosphorus, 25-OH vitamin D and 1,25(OH)2 vitamin D
      were comparable in the two groups after exclusion of those patients with
      endocrine disorders or a history of calcium and vitamin D supplementation. In
      conclusion, populations of elderly patients with sacral fractures and crush
      fractures are comparable and the occurrence of a sacral fracture is dependent on
      the presence of pelvic and/or femoral osseous abnormalities.

PMID- 8574632
TI  - Charles Bouchard.

PMID- 8574633
TI  - Superantigens in autoimmune disease.
AB  - The recent identification of superantigens (of retroviral origin in mice and
      bacterial origin in humans) has given rise to several hypotheses linking
      superantigens to autoimmune responses. The most compelling argument in support of
      such a link is restricted V beta gene usage by lymphocytes in rheumatoid joint
      fluid and Sjogren's syndrome salivary tissue. However, a substantial body of
      evidence from mouse models militates against a link between the presence of self
      superantigen-reactive T-cells and the development of autoimmune disease.
      Nevertheless, superantigens are powerful instruments for investigating tolerance.

PMID- 8574634
TI  - Isokinetic strength testing for evaluating the efficacy of intravenous immune
      globulin therapy for inclusion body myositis.
AB  - Inclusion body myositis is a disease of striated skeletal muscle of unclear
      etiopathogenesis. Its diagnosis is difficult. Corticosteroids and
      immunosuppressants are of limited efficacy. Positive responses to intravenous
      immune globulins have recently been reported in a few patients. We used a CYBEX
      6000 isokinetic dynamometer to evaluate the efficacy of intravenous immune
      globulin therapy in a patient with inclusion body myositis. Measurements were
      done at the flexors and extensors of the knee, at baseline and four and eight
      months after treatment initiation. A course of intravenous immune globulins (2 g
      per course) was given every month for five months then every two months.
      Isokinetic muscle strength measured at an angular speed of 180 degrees/second
      increased by more than 41% at both knees. As compared with muscle imaging studies
      (computed tomography, X-ray absorptiometry, ultrasonography, magnetic resonance
      imaging), isokinetic strength testing has the advantage of providing data on
      functional improvements under treatment.

PMID- 8574635
TI  - Acute calcific periarthritis of the fingers.
AB  - Two cases of acute calcific periarthritis of the fingers are described and some
      controversial clinical aspects of the syndrome discussed.

PMID- 8574636
TI  - Selective IgA deficiency in seronegative enthesopathy and arthropathy syndrome.

PMID- 8574637
TI  - Epilepsy and Paget's disease.

PMID- 8574638
TI  - Therapeutic efficacy of bromocriptine in psoriatic arthritis (two case-reports)

PMID- 8574639
TI  - High definition microfocal radiography and quantitation of radiographic features.

PMID- 8574640
TI  - Direct in vivo comparison of two mechanisms releasing dopamine in the rat
      striatum.
AB  - A push-pull cannula supplied with artificial CSF was implanted in the striatum of
      anaesthetized rats, and the basal extracellular DA and DOPAC was assayed in the
      superfusates using HPLC and electrochemical detection. Simultaneously, a carbon
      fibre electrode was implanted in close proximity of the cannula and the evoked DA
      release was detected by differential pulse amperometry during stimulation of the
      DA axons. Local treatments with cadmium (100 microM) blocked the evoked DA
      release (-90%), but substantially increased the basal extracellular DA (+125%).
      The effects of glutamate agonists NMDA (1 mM) and kainate (0.1 mM), known to
      increase basal extracellular DA were confirmed (+150% and +60% respectively). It
      was, however, simultaneously observed that the evoked DA release was inhibited (
      80% and -50%, respectively). Amphetamine (1 microM) released DA (+150%) and
      produced also an increase (+100%) of the evoked DA release. These results,
      apparently conflicting, show that the two mechanisms releasing dopamine (firing
      dependent and not) can be directly and simultaneously observed. These two
      releasing processes appear to be not strictly antagonist. They are also
      differently and independently modulated by calcium and by local influences such
      those conveyed by glutamate.

PMID- 8574641
TI  - Release of serotonin induced by 3,4-methylenedioxymethamphetamine (MDMA) and
      other substituted amphetamines in cultured fetal raphe neurons: further evidence
      for calcium-independent mechanisms of release.
AB  - The substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA), 3,4
      methylenedioxyamphetamine (MDA), p-chloro-amphetamine (PCA) and fenfluramine
      (FEN) all exert their effects by releasing serotonin (5-HT) from presynaptic
      nerve terminals. In the current study, we examined the ability of these agents to
      induce the release of 5-HT in culture fetal raphe neurons. The data indicate that
      the rank order of release potencies for these agents was (+/
      )PCA>(+)MDMA=(+)MDA=(+/-)FEN. Studies examining the role fo calcium in 5-HT
      release demonstrate that preventing calcium influx with L- and N-type calcium
      channel blockers inhibits potassium-stimulated release of -3H-5-HT but has no
      effect on release induced by the substituted amphetamines. Furthermore, omitting
      calcium from the extracellular media or depleting the vesicular pool of
      neurotransmitter with continual potassium stimulation did not affect the release
      of -3H-5-HT induced by these compounds. Administration of fluoxetine prior to the
      substituted amphetamines significantly attenuated the releasing effects of these
      agents, while producing no effect on potassium-stimulated release. These results
      are consistent with the notion that the amphetamines induce release of
      cytoplasmic 5-HT via the plasma membrane transporter.

PMID- 8574642
TI  - Stimulation of the nucleus raphe obscurus produces marked serotonin release into
      the dorsal medulla of fed but not fasted rats--glutamatergic dependence.
AB  - Serotonin interacts with TRH at the dorsal vagal complex (DVC) to augment gastric
      functional parameters. To ascertain physiologic relevance, patterns of stimulated
      release at the terminal field were characterized. Stimulation of the nucleus
      raphe obscurus (nRO) by kainic acid (423 pmol/10 nol) produced marked release of
      serotonin into dorsal medullary dialysates containing the DVC in freely fed, but
      no 24-h fasted rats. Probe infusion of kynurenic acid (1 mM), but not acute
      bilateral cervical vagotomy attenuated nRO-stimulated serotonin release in fed
      animals. The results suggest that the fed state facilitates serotonin release
      into the dorsal medulla by a mechanism mediated by activation of excitatory amino
      acid receptors in the dorsal medulla. Enhanced serotonergic neurotransmission at
      the DVC may comprise a heretofore unrecognized component of the integrated vago
      vagal response to a meal.

PMID- 8574643
TI  - Neurokinin-3 receptors modulate dopamine cell function and alter the effects of 6
      hydroxydopamine.
AB  - Neurokinin-3 receptor expression within rat midbrain dopamine neurons was
      demonstrated using a combination of in situ hybridization and receptor
      autoradiographic techniques. Continuous intranigral infusion of the neurokinin-3
      receptor agonist senktide selectively increased striatal dopamine metabolism over
      a period of several days, followed by apparent development of tolerance. In
      contrast, in animals with moderate unilateral 6-hydroxydopamine-induced lesions
      of nigrostriatal dopamine cells, intranigral senktide infusion increased dopamine
      turnover in the surviving dopamine neurons and reduced functional dopamine
      asymmetry (reflected by spontaneous rotations) over the 2-week period tested.
      Thus nigral neurokinin receptors can modulate normal dopamine cell activity and
      may provide a therapeutic target in the treatment of Parkinson's disease.

PMID- 8574644
TI  - The fate of human glial cells following transplantation in normal rodents and
      rodent models of neurodegenerative disease.
AB  - Investigations on xenografting in the brain have previously focused on the
      anatomical and functional integration of the transplanted neurons. More recently,
      astrocytes are being implicated as having complex functions following
      transplantation, and are being investigated to determine their role(s) in
      transplantation. The present study was undertaken to investigate the migration of
      human astrocytes following transplantation of thalamic, striatal, and
      mesencephalic tissue into the rodent striatum. Human donor fetuses (9-16 weeks in
      gestation) obtained through elective and spontaneous abortions were utilized in
      this study. Following transplantation, donor astrocytes were labeled with an
      antiserum directed against human glial fibrillary acidic protein. Our results
      demonstrate that astrocytic elements from all three tissue types are capable of
      incorporating into the host brain, and have a tendency to follow white matter
      tracts (such as the corpus callosum, internal capsule, and fiber bundles in the
      striatum). Human astrocytes, originating from the striatum and thalamus exhibited
      extensive migration, while migration was more limited in animals with ventral
      mesencephalon transplants. Ventral mesencephalon transplanted animal demonstrated
      positive astrocytes within the transplant, with processes (very few cell bodies)
      extending into white matter of adjacent host striatum. Astrocytes demonstrating
      immature morphology were observed with all transplant types, but were most
      prevalent in the striatal transplanted animals. The extent of astrocyte migration
      and the morphologies observed in this study reflect regional differences of the
      developing human brain. These results confirm and extend previous investigations
      on glial cell migration following transplantation in the brain.

PMID- 8574645
TI  - NADPH-diaphorase activity and Fos expression in brain nuclei following
      nitroglycerin administration.
AB  - Organic nitrates are considered nitric oxide donors in that they have been shown
      to form nitric oxide in vitro and in vivo. Nitroglycerin is an organic nitrate
      which possesses peculiar activities mediated, to some extent, by the central
      nervous system via the noradrenergic system. Previous reports have shown that
      systemic nitroglycerin is able to induce Fos expression in brain nuclei which are
      known to contain nitric oxide synthesizing enzyme. Neuronal NADPH-diaphorase has
      been shown to be a nitric oxide synthase. Thus, in this study we used NADPH
      diaphorase histochemistry to evaluate the distribution of Fos-immunoreactive
      cells within neurons which contain nitric oxide synthase. The data showed co
      localization of Fos with NADPH-diaphorase activity in numerous neurons of the
      paraventricular and supraoptic nuclei of the hypothalamus. In the brainstem, a
      few neurons were doubly labeled for Fos and NADPH-diaphorase activity, but NADPH
      diaphorase positive fibers and Fos-immunoreactive neurons were consistently co
      distributed in the locus coeruleus, parabrachial nucleus, nucleus tractus
      solitarius and spinal trigeminal nucleus caudalis. These findings demonstrate
      that nitroglycerin administration activates a selective group of neurons which
      are a source of nitric oxide or which are in close proximity with neuronal
      processes containing nitric oxide synthase, and suggest that the nitric oxide
      synthase synthesizing pathway may be involved at various levels in the central
      effect of nitroglycerin.

PMID- 8574646
TI  - The molecular switch hypothesis fails to explain the inconsistent effects of the
      metabotropic glutamate receptor antagonist MCPG on long-term potentiation.
AB  - In the CA1 region of the hippocampus, the induction of long-term potentiation
      (LTP) appears to be controlled by a switch-like biochemical process that is
      persistently activated following metabotropic glutamate receptor (mGLUR)
      activation. However, the mGLUR antagonist (RS)-alpha-methyl-4
      carboxyphenylglycine (MCPG) does not consistently block the induction of LTP,
      perhaps because the experimental conditions used by some investigators
      inadvertently activate this 'molecular switch', thereby fulfilling the
      requirement for mGLUR activation and rendering LTP insensitive to the effects of
      mGLUR antagonists. In mouse hippocampal slices we observed that MCPG does not
      block LTP induced by high-frequency stimulation, Moreover, stimulation protocols
      designed to deactivate an inadvertently activated molecular switch had no effect
      on the inability of MCPG to block LTP. MCPG (through a switch-independent
      mechanism) did inhibit the induction of LTP by a weak induction protocol. Our
      results thus suggest that MCPT-sensitive mGLURs are not required for the
      induction of LTP and that a mLGUR-activated 'molecular switch' does not explain
      the inconsistent effects of MCPG on LTP. Instead, MCPG-sensitive mGLURs may have
      a modulatory role in the induction of LTP that is most evident when LTP is
      induced by near threshold patterns of synaptic stimulation.

PMID- 8574647
TI  - Biological half-lives of zinc and manganese in rat brain.
AB  - The brains of rats injected intravenously with 65ZnCl2 or 54MnCl2 were subjected
      to high-resolution autoradiography. The distribution of 65Zn and 54Mn in each
      brain region gradually decreased from 6 days to 42 days for 65Zn and from 15 days
      to 60 days for 54Mn after the injection. The biological half-lives of Zn in each
      region studied were in the range of 16-43 days; the longest was observed in the
      amygdaloid nuclei. The regions where the long biological half-life was observed
      were consistent with the ones with the high density of Zn-containing neuron
      terminals reported previously. The biological half-lives of Mn in each region
      were 51-74 days; the longest were those in the hypothalamic nuclei and thalamus.

PMID- 8574648
TI  - Permeability of the blood-brain barrier to the neurotensin8-13 analog NT1.
AB  - Neurotensin (NT) has been suggested to be a neuropeptide with therapeutic
      potential. We used multiple-time regression analysis to measure the
      unidirectional influx constant (Ki) of a tritiated analog of NT8-13, NT1, with
      improved metabolic stability. The Ki of [3H]NT1 across the blood-brain barrier
      (BBB) was 5.12(10(-4)) ml/g-min and was decreased 66% by unlabeled NT1 system.
      The amount of NT1 crossing the BBB, 0.087% of the injected dose per gram of
      brain, is consistent with its exerting central effects after peripheral
      administration. The stable [3H]NT1 crossed the BBB in intact form as assessed by
      HPLC and completely crossed the endothelial cells that comprise the BBB as
      assessed by the capillary depletion method. The presence of a transport system
      could be important for the development of NT analogs.

PMID- 8574649
TI  - Domoic acid-induced neuronal degeneration in the primate forebrain revealed by
      degeneration specific histochemistry.
AB  - Domoic acid is a potent excitotoxin produced by diatoms which is subsequently
      passed along the marine food chain. Its chemical structure and toxicological
      properties are similar to kainic acid. Like kainic acid, exposure results in
      extensive hippocampal degeneration. The effect of domoic acid on other primate
      brain structures, however, is less resolved. In an attempt to clarify this issue,
      the present study applied a degeneration specific histochemical technique (de
      Olmos' cupric-silver method) to reveal degeneration within the brains of domoic
      acid-dosed cynomolgus monkeys. Degenerating neuronal cell bodies and terminals
      were found not only within the hippocampus, but also within a number of other
      'limbic' structures including the entorhinal cortex, the subiculum, the piriform
      cortex, the lateral septum, and the dorsal lateral nucleus of the thalamus.
      Although the hippocampus is a component of the original limbic circuit of Papez,
      other components such as the mammillary bodies, the anterior nucleus of the
      thalamus and the cingulate cortex contained no degeneration, while a number of
      more recently documented efferent targets of the hippocampal formation revealed
      extensive degeneration. The pattern of degeneration generally correlated with
      those regions containing high densities of kainate receptors.

PMID- 8574650
TI  - Cholinotoxic effects of beta-amyloid (1-42) peptide on cortical projections of
      the rat nucleus basalis magnocellularis.
AB  - Beta-amyloid(1-42) peptide (betaAP) was injected into the right nucleus basalis
      magnocellularis (nbm) of rats. After a 14-day survival time, the
      acetylcholinesterase and choline acetyltransferase activities and the number of
      muscarinic receptors were found biochemically to be significantly reduced in the
      ipsilateral frontal cortices. Confirmation of these data with silver staining
      also revealed degeneration of the projective fibers of the nbm to the frontal
      cortex. These results demonstrate the cholinotoxicity of betaAP in an in vivo
      animal model.

PMID- 8574651
TI  - Trigeminal inputs to reticulospinal neurones in lampreys are mediated by
      excitatory and inhibitory amino acids.
AB  - Reticulospinal (RS) neurones integrate sensory inputs from several modalities to
      generate appropriate motor commands for maintaining body orientation and
      initiation of locomotion in lampreys. As in other vertebrates, trigeminal
      afferents convey sensory inputs from the head region. The in vitro
      brainstem/spinal cord preparation of the lamprey was used for characterizing
      trigeminal inputs to RS neurones as well as the transmitter systems involved. The
      trigeminal nerve on each side was electrically stimulated and synaptic responses,
      which consisted of mixed excitation and inhibition, were recorded intracellularly
      in the middle and posterior rhombencephalic reticular nuclei. The EPSPs were
      mediated by activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA)/kainate receptors. An increase in the late phase of the excitatory
      response occurred when Mg2+ ions were removed from the Ringer's solution. This
      effect was antagonized by 2-amino-5-phosphonopentanoate (2-AP5) or reversed by
      restoring Mg2+ ions to the perfusate suggesting the activation of N-methyl-D
      aspartate (NMDA) receptors. IPSPs were mediated by glycine. These findings are
      similar to those reported for other types of sensory inputs conveyed to RS
      neurones, where excitatory and inhibitory amino acid transmission is also
      involved.

PMID- 8574652
TI  - Mineralization of the globus pallidus following excitotoxic lesions of the basal
      forebrain.
AB  - The excitotoxin N-methyl aspartic acid was injected into the rat nucleus basalis
      to destroy basal forebrain cholinergic (BFC) neurons. In long-term survival
      experiments (up to 11 months post-lesion), conspicuous mineralized deposits were
      found in the globus pallidus and to a lesser extent in the thalamus. Deposits
      stained in a manner consistent with a composition of calcium and iron. Typically,
      deposits were absent from the center of the injection site, where BFC cell loss
      was most severe, but were present within the ventral and lateral globus pallidus
      where there was substantial sparing of BFC neurons. The similarity of this
      pathology to basal ganglia calcification and its relationship to Alzheimer's
      Disease and Down's syndrome is discussed.

PMID- 8574653
TI  - Block of P-type Ca2+ channels in freshly dissociated rat cerebellar Purkinje
      neurons by diltiazem and verapamil.
AB  - We investigated the effects of organic Ca2+ channel blockers, diltiazem and
      verapamil, on the high voltage-activated P-type Ca2+ channels in freshly isolated
      rat Purkinje neurons. Both diltiazem and verapamil blocked P-type Ca2+ channel
      current without any change in the current-voltage relation. The block was
      concentration-dependent. In the presence of these agents, the inactivation curve
      was shifted to hyperpolarizing potentials. The characteristics of block of P-type
      Ca2+ channels by diltiazem and verapamil are similar to that of L-type Ca2+
      channels. These results indicate that both benzothiazepine and phenylalkylamine
      react with P-type Ca2+ channels and suggest that some structural features common
      to which operate in both L-type and P-type Ca2+ channels may be involved in drug
      binding to these channels.

PMID- 8574654
TI  - Responses of neurons in the caudal intralaminar thalamic complex of the rat to
      stimulation of the uterus, vagina, cervix, colon and skin.
AB  - This study examined responses of 35 neurons in the caudal intralaminar (IL)
      thalamic nuclei in 12 adult female virgin rats to mechanical stimulation of the
      skin (brush, pressure, pinch) and to 4 different visceral stimuli (noxious
      distension of the uterine horns and vaginal canal; gentle distension of the colon
      and probing the cervix). As in male rats and other species, many IL neurons
      (24/35) responded to frankly noxious somatic stimuli applied to several bodily
      regions. Some of these (16/24) also responded to one or more of the visceral
      stimuli (mainly the noxious ones), while 4/35 responded only to a visceral
      stimulus. Thus, unlike neurons in lateral thalamus studied under identical
      conditions, IL neurons appear to be signalling information primarily when intense
      somatic and visceral stimuli are frankly above the noxious threshold.

PMID- 8574655
TI  - Chronic arthritis increases tyrosine hydroxylase mRNA levels in the pontine
      noradrenergic cell groups.
AB  - In situ hybridization was used to examine the change of tyrosine hydroxylase(TH)
      mRNA levels in the pontine noradrenergic cell groups of chronic monoarthritic
      rats induced by adjuvant inoculation. The number of TH mRNA-expressing neurons
      and grains per labeled neuron in the A5,A6 and A7 cell groups on the ipsilateral
      and contralateral sides significantly increased 2 weeks after adjuvant
      inoculation into the left tibio-tarsal joint, compared to controls. These results
      suggest that noradrenalin in the pontine region may play a role in modulating
      chronic nociceptive stimuli.

PMID- 8574656
TI  - Tianeptine treatment induces regionally specific changes in monoamines.
AB  - Tianeptine is an atypical tricyclic antidepressant that facilitates serotonin (5
      HT) reuptake. Tianeptine (10 mg/kg) or saline was administered intraperitoneally
      to male rats daily for 4 days. Monoamine levels were measured in micropunches of
      discrete brain nuclei that are implicated in mood and cognition. In addition, the
      rates of 5-HT and norepinephrine (NE) accumulation were determined by the
      pargyline method. Few changes were noted in the 5-HT system. 5-HT levels were
      increased by short-term tianeptine in the CA3 region of hippocampus, and 5
      hydroxyindoleacetic acid (5-HIAA) was increased in the ventromedial nucleus of
      hypothalamus, while 5-HT turnover was decreased in preoptic area (POA). In
      addition, short-term tianeptine treatment increased NE levels in POA, parietal
      sensory cortex (SCTX) and dorsal raphe (DR), and decreased NE in dentate gyrus.
      NE turnover was also decreased in DR, SCTX and parietal motor cortex. These data
      suggest that the short-term neural and behavioral actions of tianeptine may be
      attributable, in part, to alterations of the norepinephrine system.

PMID- 8574658
TI  - The neurosteroid 3 alpha, 5 apha-THP has antiseizure and possible neuroprotective
      effects in an animal model of epilepsy.
AB  - Some anticonvulsant drugs may suppress seizures by enhancing activity of
      GABAergic systems. Progesterone (P)'s anti-convulsant and neuroprotective effects
      may be due to the steroid's actions on GABAA-benzodiazepine receptor complexes
      (GBRs) rather than intracellular progestin receptors (PRs), as many P metabolites
      have a greater effect in vitro on benzodiazepine binding and Cl-flux than P, but
      poor affinity for PRs. If P's actions are due to metabolism to a progestin more
      potent at GBRs, then systemic administration of one of those P metabolites should
      also prevent CNS damage. To test this hypothesis male rats were implanted with a
      bipolar electrode, aimed above the perforant pathway. Experimental animals
      received the 5 alpha-reduced P metabolite most effective at GBRs, 5 alpha-pregnan
      3 alpha-ol-20-one (3 alpha,5 alpha-THP) 2.5 mg/kg s.c., 3 h prior to perforant
      pathway stimulation, while control animals received sesame oil vehicle. The
      duration of chewing and drooling and the incidence of wet dog shakes, partial and
      full seizures were reduced during perforant pathway stimulation in animals pre
      treated with 3 alpha,5 alpha-THP compared to vehicle. Two weeks later, animals
      pre-treated with 3 alpha,5 alpha-THP had shorter latencies and distances to find
      a hidden platform in a Morris Water maze task. 3 alpha,5 alpha-THP pre-treatment
      also reduced damage to CA1 and CA3 layers of the hippocampus and preserved the
      number of neurons in the hilar region. These data indicate that the neurosteroid
      metabolite of P, 3 alpha,5 alpha-THP, can have anticonvulsant and may have
      neuroprotective effects in an animal model of epilepsy. Further, these data
      suggest that the mechanism of P's protective and anticonvulsant effects may be
      via GBRs rather than PRs.

PMID- 8574657
TI  - Activation of protein kinase C does not participate in disruption of the blood
      brain barrier to albumin during acute hypertension.
AB  - The blood-brain barrier minimizes the entry of macromolecules into brain tissue.
      During acute increases in arterial blood pressure, disruption of the blood-brain
      barrier occurs primarily in cerebral venules and veins. Mechanisms by which
      increases in cerebral venous pressure produce disruption of the blood-brain
      barrier during acute hypertension are not clear. The goal of this study was to
      determine the role of activation of protein kinase C in disruption of the blood
      brain barrier during acute hypertension. We examined the microcirculation of the
      cerebrum in vivo. Permeability of the blood-brain barrier was quantitated by the
      formation of venular leaky sites and clearance of fluorescent-labeled albumin
      (FITC-albumin) before and during phenylephrine-induced acute hypertension. In
      addition, we examined changes in pial arteriolar and pial venular pressure before
      and during phenylephrine-induced acute hypertension. We compared responses of the
      blood-brain barrier to acute hypertension in control (untreated) rats and in rats
      treated with inhibitors of protein kinase C; calphostin C (0.1 microM) or
      sphingosine (1.0 microM). Under control conditions, no venular leaky sites were
      visible and clearance of FITC-albumin was minimal in all groups. Phenylephrine
      infusion increased systemic arterial, pial arteriolar and pial venular pressures,
      and increased the formation of venular leaky sites and clearance of FITC-albumin
      by a similar magnitude in all groups. The findings of the present study suggest
      that inhibition of protein kinase C does not significantly alter the formation of
      venular leaky sites and/or clearance of FITC-albumin during acute hypertension.
      Thus, disruption of the blood-brain barrier during acute hypertension does not
      appear to be influenced by activation of protein kinase C.

PMID- 8574659
TI  - Heterogeneous distribution of neurons containing calbindin D-28k and/or
      parvalbumin in the rat red nucleus.
AB  - The cellular localization of calbindin D-28k (CB) and parvalbumin (PV) in the red
      nucleus of the rat was studied by means of double-immunohistochemical techniques
      applied to single sections. Neurons displaying immunoreactivity for either CB or
      PV were found throughout the rostrocaudal extent of the red nucleus, but PV
      neurons predominate in the rostral two-thirds and CB neurons in the caudal two
      thirds of the nucleus. Likewise, there was a clear but not absolute segregation
      of the two types of neurons along the dorsoventral axis; PV and CB neurons were
      largely confined to the dorsolateral and ventromedial sectors of the nucleus,
      respectively. Most CB neurons were large (> 30 microns), whereas large and medium
      sized (15-30 microns) PV neurons were equally abundant. Additionally, some large
      and medium-sized neurons displaying immunoreactivity for both PV and CB were
      encountered in the ventromedial sector of the red nucleus. The present study
      reveals that, in contrast to previous beliefs, the red nucleus is composed of a
      neuronal population that is chemically highly heterogeneous.

PMID- 8574660
TI  - Ionic mechanisms underlying burst firing in pyramidal neurons: intracellular
      study in rat sensorimotor cortex.
AB  - In in vitro slices prepared from rat sensorimotor cortex, intracellular
      recordings were obtained from 107 layer V pyramidal neurons, subsequently
      injected with biocytin for morphological reconstruction. Of the 107 neurons, 59
      (55.1%) were identified as adapting (45) or non-adapting (13) regular spiking
      neurons (RS), and 48 (44.9%) as intrinsically bursting (IB) neurons discharging
      with an initial cluster of action potentials, which tended to recur rhythmically
      in a subset of 19 cells. The block of IAR by extracellular Cs+ did not affect
      burst generation, but enhanced the tendency to reburst in IB neurons. A similar
      effect was induced by other procedures affecting K(+)-dependent post-burst
      hyperpolarization. In IB neurons Ca2+ spikes had a longer decay time than in RS
      neurons, however selective blockers of both low and high threshold Ca2+
      conductances failed to impair bursting activity. On the contrary, the perfusion
      of the slices with 0.5-1 microM TTX suppressed bursting behaviour in a critical
      time interval preceding the complete block of Na(+)-dependent action potentials.
      It is concluded that the persistent Na+ current INAP is the most important
      intrinsic factor for the typical firing properties of IB neurons, while Ca2+ and
      K+ conductances appear to contribute towards shaping bursts and controlling their
      recurrence rate. The morphology, connectivity and physiological properties of
      adapting and non-adapting RS neurons are particularly suited to the processing of
      respectively phasic and tonic inputs, whereas the properties of IB neurons are
      consistent with their suggested role in cortical rhythmogenesis and in the
      pathophysiological synchronized activities underlying epileptogenesis.

PMID- 8574661
TI  - Nitric oxide induces c-fos gene expression via cyclic AMP response element
      binding protein (CREB) phosphorylation in rat retinal pigment epithelium.
AB  - We have examined whether nitric oxide (NO) induces the expression of c-fos proto
      oncogene and the phosphorylation of cyclic AMP response element binding protein
      (CREB) in the rat retina. NO donor sodium nitroprusside (SNP) was injected into
      the vitreal cavity of the eye, and the retina and retinal pigment epithelium
      (RPE) was analysed by in situ hybridization using single-stranded RNA probes for
      c-fos transcripts and by immunocytochemistry using an anti-phospho Ser-133
      antibody 20 min after the injection of SNP, phosphorylated-CREB immunoreactivity
      was found in RPE cells and weakly in some cells of the INL. Forty-five min after
      the SNP injection, the expression of c-fos mRNA was detected in the RPE. These
      results suggested that NO induced the c-fos expression via the phosphorylation of
      CREB in RPE cells, as it has been demonstrated in PC12 cells that the
      transcription of c-fos gene was activated by the CREB phosphorylation.

PMID- 8574662
TI  - Effect of inflammatory agents on electrical resistance across the blood-brain
      barrier in pial microvessels of anaesthetized rats.
AB  - The effect of histamine, bradykinin and serotonin on blood-brain barrier
      permeability was investigated using in situ measurement of transendothelial
      electrical resistance in pial microvessels of anaesthetized rats. Mean resistance
      of vessels superfused with artificial cerebrospinal fluid was 1800 omega cm2,
      indicating a tight barrier with extremely low ion permeability. In paired
      experiments from continuous measurements in single vessels, addition of 10(-3) M
      serotonin to the solution bathing the brain had no marked effect on resistance;
      whereas both histamine and bradykinin, applied at a concentration of 10(-4) M,
      caused a rapid and reversible decrease in resistance. Mean resistance was 408 and
      505 omega cm2 in 10(-4) M histamine and bradykinin, respectively, and
      approximately 50% of vessels had a resistance less than 250 omega cm2, compared
      to 12% in controls, indicating a leaky blood-brain barrier that is not capable of
      normal brain ion homeostasis. Histamine and bradykinin had similar dose-response
      relations, and a maximal effect was observed between 20 and 50 microM. Thus,
      histamine and bradykinin act at the abluminal (brain-facing) membranes of the
      cerebral endothelium to mediate blood-brain barrier opening. These results
      support a role for histamine and bradykinin in brain oedema formation.

PMID- 8574664
TI  - Imaging the dorsal hippocampus: light reflectance relationships to
      electroencephalographic patterns during sleep.
AB  - We assessed the correspondence of 660 nm light reflectance changes from the
      dorsal hippocampus with slow wave electroencephalographic (EEG) activity during
      quiet sleep (QS) and rapid eye movement (REM) sleep in four cats. An optic probe,
      attached to a charge-coupled-device (CCD) video camera, was placed on the dorsal
      hippocampal surface to collect reflectance images simultaneously with EEG, which
      was measured by macroelectrodes placed around the probe circumference. Spectral
      estimates of EEG and light reflectance amplitude indicated that reflectance
      changes occurred in a similar frequency range as EEG changes. Dividing the image
      into 10 subregions revealed that reflectance changes at the rhythmical slow wave
      activity band (RSA, 4-6 Hz) persisted in localized regions during QS and REM
      sleep, but regional changes showed considerable wave-by-wave independence between
      areas and from slow wave electrical activity. Peak frequencies for reflectance
      changes corresponded to fast RSA frequencies observed in the EEG. Optical changes
      most likely derive from fast-acting physical phenomena, rather than from
      alterations in blood perfusion, and provide increased spatial resolution over
      that offered by electrical measurements.

PMID- 8574663
TI  - Dynamic analysis of ethanol effects on NMDA-evoked dopamine overflow in rat
      striatum.
AB  - This study was undertaken to dynamically examine the effects of ethanol on the
      striatal dopaminergic transmission, in terms of N-methyl-D-aspartate (NMDA)
      evoked dopamine release and dopamine uptake. In the striatum of urethane
      anesthetized Sprague-Dawley rats, extracellular dopamine was measured using in
      vivo electrochemical detection coupled with a nafion-coated carbon fiber working
      electrode. Micro-ejection of NMDA evoked a transient dopamine release from the
      dopamine-containing nerve terminals in striatum. Local application of ethanol by
      pressure ejection did not elicit significant changes in spontaneous dopamine
      release. However, with ethanol pretreatment, the time course of NMDA-induced
      dopamine release was markedly prolonged while the magnitude and the rate of
      clearance were significantly reduced. These effects were compared to those of
      nomifensine, a dopamine uptake blocker. Nominfensine pretreatment was found to
      augment the time course of NMDA-evoked dopamine release analogous to those by
      ethanol pretreatment. Furthermore, pretreatment with ethanol did not increase the
      time course parameters of dopamine signals if dopamine releases were induced by
      co-application of NMDA and nominfensine. These data suggest that in addition to
      the attenuation of NMDA-evoked dopamine release, ethanol inhibits dopamine uptake
      in a similar fashion to that observed with nomifensine in situ in the striatum.
      Indeed, ethanol altered the uptake of exogenous dopamine from the extracellular
      space of striatal cortex. The time course of dopamine signals was prolonged and
      the rate of clearance was reduced after ethanol treatment. Taken together, our
      data demonstrate that ethanol simultaneously inhibits NMDA-evoked dopamine
      release and dopamine uptake in the striatum, suggesting the importance of the
      interplay between release and uptake in ethanol effects on striatal dopaminergic
      transmission.

PMID- 8574665
TI  - The effect of post-asphyxial reoxygenation with 21% vs. 100% oxygen on Na+,K(+)
      ATPase activity in striatum of newborn piglets.
AB  - To compare the effect of 21% vs. 100% oxygen during post-asphyxial reoxygenation
      on brain cell membrane function in the striatum, 20 anesthetized, ventilated
      newborn piglets were studied: group 1 (normoxia, n = 5), group 2 (asphyxia, no
      reoxygenation, n = 5), group 3 (asphyxia followed by reoxygenation with 21% O2, n
      = 5), and group 4 (asphyxia followed by reoxygenation with 100% O2, n = 5).
      Asphyxia was induced by a stepwise reduction in FiO2 at 20 min intervals from 21%
      to 14%, 11%, and 8%. Following a total 60 min of asphyxia, piglets in groups 3
      and 4 were recovered for 2 h with either 21% or 100% O2. Na+,K(+)-ATPase activity
      (mumol Pi/mg protein/h) in striatal cell membranes was 31 +/- 1, 22 +/- 2, 32 +/-
      2 and 26 +/- 1 in groups 1, 2, 3 and 4, respectively. Na+,K(+)-ATPase activities
      in groups 2 and 4 were significantly lower than in groups 1 and 3 (p < 0.01).
      Piglets recovered post-asphyxia for 2 h with 21% O2 had restoration of Na+,K(+)
      ATPase activity to baseline levels, while those treated with 100% O2 during
      recovery had persistent Na+,K(+)-ATPase inhibition of 16%. This could result from
      increased free radical production during reoxygenation with 100% O2 which could
      contribute to post-asphyxial cellular injury in the striatum.

PMID- 8574666
TI  - 192IgG-saporin-induced immunotoxic lesions of cholinergic basal forebrain system
      differentially affect glutamatergic and GABAergic markers in cortical rat brain
      regions.
AB  - To study the effect of reduced cortical cholinergic activity on GABAergic and
      glutamatergic mechanisms in cholinoceptive cortical target regions a novel
      cholinergic immunotoxin (conjugate of the monoclonal antibody 192IgG against the
      low-affinity nerve growth factor receptor with the cytotoxic protein saporin) was
      applied, which specifically and selectively destroys cholinergic cells in rat
      basal forebrain nuclei. To correlate the responses to cholinergic immunolesion in
      cholinoceptive cortical target regions with cholinergic hypoactivity,
      quantitative receptor autoradiography to measure NMDA, AMPA and kainate glutamate
      receptor subtypes, GABAA and benzodiazepine receptors as well as choline uptake
      sites, and histochemistry to estimate acetylcholinesterase activity were
      performed in adjacent brain sections. One week after a single intraventricular
      injection of 4 micrograms of 192IgG-saporin, NMDA receptor binding was markedly
      reduced in cortical regions displaying a reduced activity of acetylcholinesterase
      and high-affinity choline uptake sites as a consequence of cholinergic lesion,
      whereas AMPA and kainate binding sites were significantly increased in these
      regions. Muscimol binding to GABAA receptors was increased in the caudal portions
      of frontal and parietal cortices as well as occipital and temporal cortex as
      compared to the corresponding brain regions from vehicle-injected control rats.
      Binding levels of benzodiazepine receptors were not affected by the lesion in any
      of the cortical regions studied. The differential changes in glutamate and GABA
      receptor subtypes following cholinergic immunolesion might be regarded as the
      consequence of a cortical reorganization compensating for the reduced cholinergic
      presynaptic input. The data further suggest that presynaptic cortical cholinergic
      deficits might affect both glutamatergic and GABAergic functions with different
      intensity and different directions.

PMID- 8574667
TI  - Lesions of the medial prefrontal cortex and sexual behavior in the male rat.
AB  - Lesions of the cerebral cortex near the midline in the frontal region appearing
      to destroy most of the cingulate cortex and adjacent prefrontal areas had
      profound effects on male rat sexual behavior. At the first postoperative tests,
      one week after the lesion, the mount and intromission latencies were extremely
      long (> 60 min). They continued elevated at every fortnightly test until
      postlesion week 13, when they were no longer different from controls. However,
      the proportion of animals that intromitted or ejaculated was reduced at this
      time. The lesion had a slight effect on the number of intromissions and on the
      intromission ratio, but did not reliably modify other parameters of sexual
      behavior in those males that copulated after operation. These data suggest that
      the medial prefrontal cortex is important for the initiation of sexual behaviour
      but less so for its execution. It is proposed that the elaboration and/or
      interpretation of environmental stimuli are rendered deficient by the lesion.
      Consequently, sexual behavior is activated only with difficulty. This coincides
      with the arousal hypothesis proposed by Beach [8]. There appears to exist a
      spontaneous recovery of the mechanisms responsible for the activation of sex
      behavior because the lesioned group was not different from the sham or intact
      groups 13 weeks postlesion. Remaining cortical tissue or other brain structures
      may compensate for the initial deficiencies. However, the lesion's effect on
      intromission behavior did not diminish with time. This could suggest that
      possible motor deficiencies produced by the lesion are irreversible.

PMID- 8574668
TI  - Central nervous stimulants facilitate sexual behavior in male rats with medial
      prefrontal cortex lesions.
AB  - Male rats with lesions of the cerebral cortex near the midline in the frontal
      region destroying most of the cingulate cortex and producing some damage to
      adjacent frontal areas have very long mount and intromission latencies. Otherwise
      their sexual behavior is essentially normal. The dopamine releasers amfonelic
      acid, 0.5 mg/kg, and amphetamine, 1 mg/kg, reduced the mount and intromission
      latencies in males with such lesions. Caffeine, 30 mg/kg, had similar effects.
      None of the drugs modified sexual behavior in intact males. It has been suggested
      that medial prefrontal lesions reduce the animal's reactivity to environmental
      stimuli, and hence renders the activation of sexual behavior difficult. Present
      results show that stimulant drugs are capable of compensating for this reduced
      reactivity. The possible mechanisms behind this effect are discussed. The lesion
      had also a small but consistent effect on the intromission ratio, suggesting some
      motor impairment. The effect on intromission ratio was not reduced by the drugs,
      suggesting that the lesion's motor consequences are mediated by mechanisms
      different from those controlling behavioral reactivity. The noradrenaline
      precursor dl-threo-dihydroxyphenylserine, 10 mg/kg, in combination with
      carbidopa, 50 mg/kg, increased mount and intromission latencies in both intact
      and lesioned males. Thus, activation of noradrenergic neurotransmission had
      effects opposite to those found after activation of dopaminergic transmission.
      Noradrenergic stimulation cannot, therefore, be important for the effects of
      amphetamine or amfonelic acid.

PMID- 8574669
TI  - Quantitative analysis of factors influencing neuronal necrosis induced by MK-801
      in the rat posterior cingulate/retrosplenial cortex.
AB  - A single dose of the non-competitive NMDA receptor antagonist MK-801 (dizocilpine
      maleate) induces neuronal necrosis in the posterior cingulate/retrosplenial
      (PC/RS) cortex of adult rats. The present studies further characterized this
      effect and evaluated several variables that affect its expression. Male and
      female rats of two strains (Sprague-Dawley and Fischer 344) and two ages (70 and
      127 days) were given a single subcutaneous injection of vehicle (water) or MK-801
      (0.5, 1.0 or 5.0 mg/kg). A simple behavioral response (recumbency) and number of
      necrotic neurons in the PC/RS cortex were evaluated. MK-801 induced dose
      dependent recumbency which was more severe and of longer duration in females of
      either strain or age. In addition, female rats (regardless of strain, dose, or
      age) consistently had significantly more necrotic PC/RS neurons than male rats.
      In a second study, a high dose of MK-801 was given intraperitoneally (10 mg/kg)
      to male and female Sprague-Dawley rats (90-120 days of age). Necrotic neuron
      counts were determined at 5 separate rostrocaudal levels of the PC/RS cortex. At
      levels where neuronal necrosis occurred, the magnitude of the effect was
      significantly greater in females than males and the number of necrotic neurons
      increased along a rostral to caudal gradient. Our findings indicate that (1) MK
      801 dose dependently induces recumbency and necrosis of PC/RS cortical neurons in
      both Sprague-Dawley and Fischer 344 rats, (2) female rats of either strain are
      more sensitive than their male counterparts, and (3) the extent of necrosis of
      PC/RS cortical neurons increases along a rostral to caudal gradient.

PMID- 8574670
TI  - Inhibitory effects of electrical stimulation of thalamic nucleus submedius area
      on the rat tail flick reflex.
AB  - This study in lightly anesthetized rats found that unilateral electrical
      stimulation delivered to the ventral part of the thalamic nucleus submedius (Sm),
      the thalamic reuniens nucleus (Re) and the hypothalamic dorsal area (DA) markedly
      depressed the TF reflex, and this inhibitory effect increased following
      increasing stimulation intensity. Stimulation in the dorsal part of Sm did not
      produce any or only slight depression of the TF reflex. Furthermore, an
      ipsilateral electrolytic lesion of the ventrolateral orbital cortex (VLO)
      eliminated the unilateral Sm-evoked inhibition, but not the inhibition elicited
      by Re and DA and contralateral Sm stimulation. Finally, after bilateral
      electrolytic lesions of the ventrolateral periaqueductal gray (PAG) the DA and Re
      and contralateral Sm-evoked inhibitions were also eliminated. The results suggest
      that the Sm plays an important role in modulation of nociceptive inputs, and this
      role of Sm is mediated by the VLO and leads to activation of the PAG descending
      inhibitory system and depression of the nociceptive inputs at the spinal cord
      level.

PMID- 8574671
TI  - Immunohistochemical determination of rat spinal cord substance P, and
      antinociceptive effect during development of thiamine deficiency.
AB  - During 30 days of thiamine deficiency (TD) feeding, the rat antinociceptive
      effect (pain threshold) to noxious heat stimulation was significantly increased
      in proportion to the decrease substance P (SP) fluorescent intensity in the
      spinal cord. Only a single injection of thiamine HCl (0.5 mg/kg, s.c.) on the
      early treatment day during TD feeding effectively reversed the analgesic effect
      to the pair-fed control level. Whereas this reversal effect by thiamine treatment
      was not found if this treatment was done on the relatively late day. However,
      either treatment day, except muricide, complete disappearance of various animal
      behaviours induced by TD was found. These results indicate that, after certain
      degree of TD development, TD-induced behavioral effects might be reversible, but
      the afferent nerve fibers might be irreversibly damaged, probably by the similar
      mechanism as found for an excitotoxin(s) mediated injury in the certain brain
      region(s). The results also suggest a possibility that SP and an excitotoxin,
      glutamate, in the dorsal part of the spinal cord greatly contribute to the pain
      transmission induced by noxious heat stimulation.

PMID- 8574672
TI  - Brain 2-deoxyglucose levels related to maternal behavior-inducing stimuli in the
      rat.
AB  - Levels of [14C]2-deoxyglucose (2-DG), measured autoradiographically, in the
      medial preoptic area (MPOA), were higher during natural parturition with
      concurrent maternal behavior than in non-pregnant non-maternal controls, whereas
      levels in the vomeronasal system were lower in virgin rats made maternal by
      cohabitation with young than in control and parturient rats. Previous studies
      have shown that lesions of MPOA disrupt maternal behavior, whereas lesions of
      vomeronasal structures stimulate it, and that an increase in 2-DG levels is
      indicative of an increase in firing activity in neuron terminals. Consequently,
      the present findings suggest that maternal behavior can be induced by: (a) an
      increase in parturition-generated sensory stimulatory input to the MPOA in
      response to mechanostimulation of the birth canal, and (b) a separate
      chemosensory vomeronasal pathway whose activity is reduced cohabitation with
      young, thereby disinhibiting maternal behavior.

PMID- 8574673
TI  - Local preoptic/anterior hypothalamic warming alters spontaneous and evoked
      neuronal activity in the magno-cellular basal forebrain.
AB  - Local warming of the medial preoptic/anterior hypothalamus (POAH) promotes sleep,
      enhances EEG slow-wave activity during sleep, and suppresses arousal-related
      discharge in neurons of the midbrain reticular formation (MRF) and the posterior
      lateral hypothalamic area (PLHa). Another important site of sleep and arousal
      regulation, and a potential site of POAH thermal modulation, is the magnocellular
      basal forebrain (BF). We examined the ability of local POAH warming during
      wakefulness to influence the spontaneous and evoked discharge of neurons recorded
      in the BF of unanesthetized, unrestrained cats. Seventy of 174 BF neurons
      responded to 60-90 s periods of POAH warming with either increases or decreases
      in discharge rate. Forty-one of the 70 responsive cells displayed suppression of
      waking discharge during warming. Discharge rate in these cells declined by an
      average of 26.04 +/- 2.76%/degrees C of POAH temperature increase. The majority
      of warming-suppressed BF cells (73%) displayed higher rates of discharge during
      periods of wakefulness compared to periods of sleep. Twenty-nine of 70 responsive
      cells responded to POAH warming with an average increase in discharge rate of
      43.81 +/- 6.26%/degrees C. A majority of these neurons (62%) exhibited higher
      spontaneous discharge rates during sleep compared to waking. Orthodromic
      excitatory responses were evoked in 29 BF cells by electrical stimulation of the
      MRF or PLHa. Thirteen of 29 cells displayed a waking-related discharge pattern,
      and responded to POAH warming with a significant suppression of evoked
      excitation. For a group of 15 behavioral state-indifferent cells (i.e., cells
      displaying no modulation of spontaneous discharge rate across the sleep-waking
      cycle), POAH warming had no effect on evoked excitatory responses. These results
      support the hypothesis that thermosensitive neurons of the POAH exert control of
      sleep-waking state, in part, via modulation of arousal- and sleep-regulating cell
      types within the magnocellular BF.

PMID- 8574674
TI  - Effect of extracellular K+ on the intracellular free Ca2+ concentration in leech
      glial cells and Retzius neurones.
AB  - The effects of extracellular K+ on the intracellular free Ca2+ concentration
      ([Ca2+]i) of neuropile glial cells and Retzius neurones in intact segmental
      ganglia of the leech Hirudo medicinalis were investigated by using
      iontophoretically injected fura-2. In both cell types, an elevation of the
      extracellular K+ concentration ([K+]o) caused an increase in [Ca2+]i, which was
      blocked by Co2+, Ni2+ and menthol, whereas nicardipine, flunarizine, omega
      conotoxin GVIA and omega-agatoxin IVA were ineffective. In Ca(2+)-free solution,
      the K(+)-induced [Ca2+]i increase was largely suppressed in neuropile glial cells
      and completely abolished in Retzius neurones. The results indicate that the K(+)
      induced [Ca2+]i increase was mainly due to Ca2+ influx through voltage-dependent
      Ca2+ channels. The Ca2+ channels of the two cell types were activated at
      different membrane potentials but at the same [K+]o. In both cell types, the
      recovery from a K(+)-induced [Ca2+]i increase was unaltered in Na(+)-free
      solution, indicating that active Ca2+ transport across the plasma membrane is
      mediated by Na(+)-independent mechanisms.

PMID- 8574675
TI  - Involvement of class A calcium channels in the KCl induced Ca2+ influx in
      hippocampal synaptosomes.
AB  - Using Ca2+ channel toxins, we determined the types of voltage-sensitive calcium
      channels activated by two levels of KCl depolarization in hippocampal
      synaptosomes. The increase in the intracellular Ca2+ concentration ([Ca2+]i)
      induced by 30 mM KCl was equally sensitive to either omega-agatoxin IVA (omega
      Aga IVA) or to omega-conotoxin MVIIC (omega-CgTx MVIIC), and the inhibition
      produced by these two peptides was not additive. The present results indicate
      that omega-Aga IVA and omega-CgTx MVIIC do not distinguish between two different
      VSCC in hippocampal synaptosomes and that they both inhibit a channel with the
      alpha 1A subunit which is present in the rat hippocampus.

PMID- 8574676
TI  - Transsynaptic localization of pharyngeal premotor neurons in rat.
AB  - We determined the anatomy and connectivity of the brainstem circuit controlling
      the buccopharyngeal phase of swallowing, using pseudorabies virus to identify
      linked circuits of neurons. Pharyngeal vagal afferents terminate on premotor
      neurons in the interstitial and intermediate subnuclei of the nucleus of the
      solitary tract, which in turn, innervate pharyngeal motoneurons in the
      semicompact subnucleus of the nucleus ambiguus. This circuit is separate and
      distinct from the esophageal swallowing circuit.

PMID- 8574677
TI  - Caffeine attenuates CNS oxygen toxicity in rats.
AB  - We tested the effect of caffeine, on hyperoxia-induced seizures. Thirty-seven
      rats with chronic cortical electrodes were injected i.p. with caffeine (1.25,
      2.5, and 10 mg/kg) or vehicle before exposure to 0.5 MPa oxygen and 17 rats to
      oxygen with 5% CO2 at 0.5 MPa. EEG monitoring and spectral analysis of EEG
      activity were carried out. Caffeine significantly prolonged the latent period to
      the onset of seizures (P < 0.05 in ANOVA), in a dose-related manner. Our results
      suggest that caffeine may be used in low doses for protection against hyperoxia
      induced seizures.

PMID- 8574678
TI  - Dipsogenic effect of pituitary adenylate cyclase activating polypeptide (PACAP38)
      injected into the lateral hypothalamus.
AB  - PACAP38 bilaterally injected in the vicinity of the perifornical lateral
      hypothalamus (pfLH) induced drinking behavior in rats. The animals (n = 12) drank
      19.7 +/- 4.1 ml of water during the hour following PACAP38 microinjections (1
      nmol/0.5 microliter). In the same rat sulpiride microinjections (45 nmol/0.5
      microliter) had relatively mild effects (7.8 +/- 1.4 ml/h). The dipsogenic
      effects of sulpiride and PACAP38 were well correlated suggesting that both
      substances trigger drinking behavior activating the same hypothalamic mechanisms.
      Neither sulpiride nor PACAP38 promoted drinking when injected just 1.3 mm behind
      the effective zone. This negative result is an evidence of the neuroanatomical
      specificity of the dipsogenic effects of both substances. These preliminary
      results suggest that PACAP38 in the pfLH could be a neuropeptide regulating
      drinking behavior and perhaps body fluid volume and osmolarity and arterial blood
      pressure.

PMID- 8574679
TI  - Effects of inhibitory amino acids on the frequency components in sympathetic
      nerve discharge.
AB  - The effects of the GABA antagonist picrotoxin and the glycine antagonist
      strychnine on the frequency components in sympathetic inferior cardiac nerve
      activity were observed. Picrotoxin (0.03-1.0 mg/kg) increased power in the 10-Hz
      component of sympathetic activity and produced a dramatic shift in the rhythm to
      higher frequencies. Only small changes were noted in the 2- to 6-Hz component.
      Strychnine produced a small generalized increase in power in both frequency bands
      in sympathetic activity. These data suggest that GABA may play an important role
      in the generation and maintenance of the 10-Hz rhythm in sympathetic activity
      while glycine likely inhibits activity at a site of convergence of the two
      rhythms in sympathetic activity.

PMID- 8574680
TI  - Morphological abnormalities in the hippocampus of the weaver mutant mouse.
AB  - The lamination of the hippocampus in the homozygous B6CBA weaver mouse (wv/wv)
      was compared with that in normal B6CBA littermates (+/+) and C57BL/6J mice using
      Nissl and Timm's staining. In Nissl-stained preparations, the normal littermates
      exhibit a compact, regular arrangement of pyramidal cells in area CA3 of the
      hippocampus. In contrast, in homozygous weaver mutant mice, the pyramidal cell
      layer of area CA3 frequently appears to be thicker than normal with an apparent
      increase of neuropil, as evidenced by the presence of cell-free spaces within the
      layer. Also, small ectopic clusters of pyramidal cells and sometimes the
      subdivision of the pyramidal cell layer into 2 or 3 layers were found throughout
      the dorsoventral extent of the hippocampus. In Timm's stained preparations of the
      normal mouse hippocampus, two clearly separated bundles of axons were seen
      emerging from the hilus: one bundle running above the pyramidal cell layer of
      area CA3 (i.e., the suprapyramidal mossy fiber layer, SPMFL), and the second
      bundle running below the pyramidal cell layer (i.e., the infrapyramidal mossy
      fiber layer, IPMFL). In contrast, in some homozygous weaver mice, the origin of
      the mossy fiber bundles is clearly different from normal; specifically, mossy
      fibers emerge in a diffuse fashion from the area between suprapyramidal and
      infrapyramidal mossy fiber layers. In other weaver mice, short, discontinuous
      bundles diverge from the infrapyramidal mossy fiber layer and invade the
      thickened pyramidal cell layer. In addition, ectopic pyramidal cells are situated
      below the IPMFL in area CA3. The morphological changes observed in hippocampus of
      weaver mutants are likely to be secondary to a more basic genetic defect.

PMID- 8574681
TI  - Evidence for oxidative stress in Pick disease and corticobasal degeneration.
AB  - Oxidative stress is increasingly implicated in a number of neurodegenerative
      disorders characterized by abnormal filament accumulation in affected neurons,
      including Alzheimer disease, Parkinson disease, and amyotrophic lateral
      sclerosis. To further evaluate the role of oxidative stress in the
      neurodegenerative process and the accumulation of abnormal filaments, we examined
      the pathologic lesions in Pick disease and of corticobasal degeneration with
      immunocytochemistry by using antisera to heme oxygenase-1 (HO-1) - a putative
      marker of oxidative injury. Immunoreactivity to HO-1 was demonstrated in
      ballooned neurons, Pick bodies, neuropil threads, and glial inclusions (the
      latter two in a case of corticobasal degeneration). By immunoelectron microscopy,
      HO-1 immunolabelling of Pick bodies was closely associated with the abnormal
      filaments comprising the inclusion. Apparently unaffected neurons in all cases
      showed only background levels of HO-1 immunoreactivity. These data suggest that
      oxidative stress is important in the formation of the lesions characteristic of
      Pick disease and corticobasal degeneration. Moreover, taken together with our
      previous demonstration that HO-1 immunoreactivity is associated with the
      neurofibrillary pathology of Alzheimer disease, progressive supranuclear palsy,
      and subacute sclerosing panencephalitis, it appears that oxidative stress
      specifically targets the cytoskeleton in a variety of neurodegenerative disorders
      characterized by abnormal filament accumulation.

PMID- 8574682
TI  - Ultrastructural localization and translocation of nitric oxide synthase in the
      endothelium of the human cerebral artery.
AB  - An electron microscopic immunocytochemical study was undertaken to clarify
      ultrastructural localization and translocation of nitric oxide synthase (NOS) in
      endothelial cells (EC) of the human cerebral and superficial temporal arteries
      (STA) employing antibody against endothelial NOS (EC-NOS). NOS immunoreactivity
      was found in all EC examined, in association with the plasma membrane and
      cytoplasmic organelles such as endoplasmic reticulum, Weibel-Palade body and
      subplasmalemmal vesicles, and in the cytoplasm devoid of organelles and
      extracellular regions, irrespective of arteries. The immunoreactivity in
      subplasmalemmal vesicles was, however, demonstrated only in human cerebral
      arteries. In the human STA exposed to bradykinin which induces EC-NOS
      phosphorylation, the gold particles significantly increased in the cytosol and
      decreased in the areas associated with cytoplasmic organelles; however, the
      number of particles did not change significantly in the plasma membrane. The
      results implicate that NOS may be translocated from the area associated with
      cytoplasmic organelles to cytosol following EC exposure to bradykinin.

PMID- 8574683
TI  - Human hydroxyindole-O-methyltransferase in pineal gland, retina and Y79
      retinoblastoma cells.
AB  - Hydroxyindole-O-methyltransferase (HIOMT, EC 2.1.1.4) was studied in extracts of
      human pineal gland, retina and Y79 retinoblastoma cells. HIOMT enzyme activity
      and immunoreactive protein (approximately 42 kDa) were undetectable in the human
      retina; very low levels of HIOMT mRNA were detected using a highly sensitive RT
      PCR/Southern blot method, as has been reported. Analysis of extracts of Y79 cells
      indicated that HIOMT enzyme activity, immunoreactivity (approximately 42 kDa) and
      mRNA (approximately 1.3 kb) were detectable at approximately 1/5-1/40 the levels
      found in the pineal gland. This unambiguously establishes that the HIOMT gene is
      expressed in Y79 cells. Kinetic analysis of Y79- and pineal-derived HIOMT
      indicates that the enzyme is generally similar in both tissues; one difference,
      however, is that substrate inhibition by N-acetylserotonin is greater with the
      Y79-derived enzyme. These studies show that Y79 cells represent a valid model to
      study the regulation of human HIOMT protein and mRNA; the differences detected
      may reflect the existence of tissue-specific regulatory mechanisms or
      differential patterns of expression of HIOMT isoforms.

PMID- 8574684
TI  - S-100 beta has a neuronal localisation in the rat hindbrain revealed by an
      antigen retrieval method.
AB  - The localisation of S-100 in mammalian CNS neurons has been under debate for more
      than two decades. We address the question with two polyclonal and two new
      monoclonal antibodies. The specificity and the distribution in rat brain is based
      on an antigen retrieval method. We present evidence that aldehyde fixatives mask
      S-100 beta in neurons, and that the immunoreactivity is retrieved after
      trypsinisation. Neuronal S-100 beta is also detected in unfixed and ethanol fixed
      sections. The neuronal immunoreactivity is partly solubilised from unfixed tissue
      sections with 2.5 mM EDTA and is completely extracted with 2.5 mM EDTA and 1%
      Triton X-100. Most of the glial S-100 beta is washed out from unfixed tissue
      sections with saline. S-100 beta has distinct distribution in neurons of the
      hindbrain, i.e., the brainstem and cerebellum, but is not observed in the
      forebrain. One of the monoclonal antibodies immunostained neither neurons nor
      glia when it had been absorbed with S-100 crosslinked to nitrocellulose
      membranes. The distribution of neuronal S-100 beta differed from that of other
      neuronal calcium binding proteins, such as calbindin and parvalbumin. It was
      confined mainly to cholinergic neurons of the hindbrain. The presence of S-100
      beta in distinct neuronal populations may indicate neurotrophic effects of S-100
      beta. The notion is supported by the capability of S-100 to cause neurite
      outgrowth in vitro.

PMID- 8574685
TI  - Extracellular concentrations of serotonin in the dorsal hippocampus after acute
      and chronic treatment with citalopram.
AB  - Citalopram, 1 and 10 mg/kg i.p., that in a previous study using identical
      treatment and dialysis conditions had little or no effect on dialysate serotonin
      (5-HT) in the frontal cortex, dose-dependently raised the extracellular
      concentrations of 5-HT in the dorsal hippocampus, by 70% and 205% respectively at
      the peak. In animals given 10 mg/kg citalopram twice daily for 14 days,
      intraperitoneal doses of 1 and 10 mg/kg or infusion of 10(-8) - 10(-6) M through
      the hippocampal probe raised dialysate 5-HT in the dorsal hippocampus similarly
      in animals treated chronically with citalopram or saline. A dose of 100
      micrograms/kg 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), an agonist at 5
      HT1A receptors, reduced hippocampal extracellular 5-HT concentrations to the same
      extent in rats repeatedly given saline or citalopram. Half this dose had no such
      effect in either group. The effect of citalopram and the sensitivity of
      autoreceptors controlling 5-HT release in the dorsal hippocampus were unaffected
      by a chronic treatment known to facilitate the drug's effect on dialysate 5-HT
      and to reduce the sensitivity of 5-HT1A receptors controlling 5-HT release in the
      frontal cortex. The effects of acute and chronic treatment with citalopram on
      dialysate 5-HT in the rat brain thus appear to differ in at least two brain
      regions: the frontal cortex and the dorsal hippocampus.

PMID- 8574686
TI  - Muscarinic receptor agonist-induced increases in cytosolic Ca2+ concentrations in
      chick ciliary ganglion cells.
AB  - We used fura-2 microfluorometry to examine the mechanism underlying the
      muscarinic receptor agonist-induced increase in the cytosolic Ca2+ concentration
      ([Ca]in) in acutely isolated chick ciliary ganglion neurons. The order of
      potencies of muscarinic agonists in increasing [Ca]in was: oxotremorine M >
      muscarine > methacholine > oxotremorine > bethanechol. The muscarine-induced
      increase in [Ca]in persisted after treatment with thapsigargin, which blocked
      caffeine- and muscarinic agonist-induced Ca2+ release. The muscarine-sensitive
      [Ca]in increase was inhibited by both L- and N-type Ca2+ channel blockers but
      potentiated by an L-type Ca2+ channel agonist. Muscarine was effective in
      increasing [Ca]in in the presence of a desensitizing concentration of nicotine,
      and simultaneous addition of maximal doses of muscarine and nicotine caused an
      additive increase in [Ca]in. On the other hand, nicotine-, ATP-, and high K(+)
      induced increase in [Ca]in was markedly potentiated during continuous stimulation
      with muscarine. These results suggest that muscarinic receptor stimulation
      increases Ca2+ influx passing through voltage-dependent Ca2+ channels. However,
      the muscarine-induced Mn2+ influx was observed in only some muscarine-sensitive
      cells, suggesting that muscarine-induced depolarization is too weak to overcome
      the inhibitory effect of Mn2+ on Ca2+ channels.

PMID- 8574687
TI  - A confocal approach to the morphofunctional characterization of the transient
      tyrosine hydroxylase system in the rat suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus (SCN) of the neonatal rat is transiently innervated
      by tyrosine hydroxylase (TH) fibers of unknown origin and whose catecholaminergic
      nature is rather doubtful. In order to characterize this system
      morphofunctionally, immunocytochemical double labelling and confocal laser
      scanning microscopy analysis were employed on cryostat brain sections of 10-day
      old rats. Simultaneous stainings for neuropeptide Y (NPY) and tyrosine
      hydroxylase (TH) immunoreactivity showed that they are not colocalized, neither
      in the SCN fibers nor in the intergeniculate leaflet (IGL) neurons, site of
      origin of the NPY projection to the SCN. Therefore, the possibility that SCN
      transient TH fiber system originates from the IGL could be excluded. Double
      labelling for TH and aromatic L-aminoacid decarboxylase (AADC) demonstrated that
      transient SCN TH immunoreactive (IR) fibers are AADC negative, thus supporting
      the hypothesis of their non-catecholaminergic nature. Moreover two new group of
      cells which are TH positive and AADC negative were found: one in the SCN and the
      other in the periventricular hypothalamic nucleus (PHN). The presence of
      somatostatin (SRIF) and TH in PHN neurons and SCN fibers suggested their possible
      colocalization, but double immunolabellings gave negative results. Simultaneous
      immunocytochemical staining for vasoactive intestinal polypeptide (VIP) and TH
      showed that TH fibers may interact with ventrolateral SCN VIP neurons. This
      result suggests a possible involvement of TH fibers in regulating VIP cells
      activity in the entrainment of circadian rhythms.

PMID- 8574688
TI  - The effect of aging on efferent nerve fibers regeneration in mice.
AB  - This study evaluates the influence of aging on nerve regeneration and
      reinnervation of target organs in mice aged 2, 6, 9, 12, 18 and 24 months. In
      animals of each age group the sciatic nerve was subjected to crush, section or
      section and suture. Reinnervation of plantar muscles and sweat glands (SG) was
      evaluated over three months after operation by functional methods. Reappearance
      of SG secretion and motor responses occurred slightly earlier in young than older
      mice. The degree of motor and sudomotor reinnervation, with respect to
      preoperative control values, was also significantly higher in young than old
      animals. The differences were more pronounced after 12 months of age. The degree
      of recovery progressively decreased with the severity of the lesion, differences
      being more marked in older mice. Neurorraphy improved recovery, comparatively
      more in older than in young mice. These results indicate that, after injuries of
      peripheral nerves, axonal regeneration and reinnervation are maintained
      throughout life, but tend to be more delayed and slightly less effective with
      aging.

PMID- 8574689
TI  - Alterations in L-type calcium channels in the brain and spinal cord of acutely
      treated and morphine-tolerant mice.
AB  - Opiate tolerance has been associated with changes in neuronal intracellular
      calcium levels. In vivo studies have indicated the involvement of dihydropyridine
      (DHP)-sensitive ('L-type') voltage-gated calcium channels in the morphine
      tolerant state. In this study, we assessed how the morphine-tolerant state would
      affect the antinociception produced by intrathecal administration of two agents
      (Bay K 8644 and thapsigargin) that increase intracellular calcium. Morphine
      tolerant mice displayed a 7-fold greater ED50 for Bay K 8644 antinociception than
      placebo-treated animals; no difference was found in the dose-response curve for
      thapsigargin. To further explore the role of the L-type channel in morphine
      tolerance development, we performed radiolabeled nitrendipine binding studies in
      the spinal cord and brain regions associated with pain modulation from acutely
      treated, tolerant, and control mice. Our treatment protocol produced a 4-fold
      shift in the ED50 for s.c. morphine antinociception, as determined by the tail
      flick procedure. Binding site number and affinity were determined using Scatchard
      analysis for the following timepoints: 20 min and 60 min after s.c. injection of
      morphine or vehicle, as well as after 4 days of chronic administration, and after
      naloxone-precipitated withdrawal. Although some changes were observed in the
      affinity of nitrendipine for its receptor, a significant change in these measures
      was found only following naloxone administration, which produced increases in
      Bmax in both placebo- and morphine-treated mice.

PMID- 8574690
TI  - Region-specific alterations of calbindin-D28k immunoreactivity in the rat
      hippocampus following adrenalectomy and corticosterone treatment.
AB  - The aim of this study was (i) to compare the immunocytochemical distribution of
      the calcium-binding protein calbindin-D28k (CB) in the hippocampus of rats with
      the pattern of neurodegeneration following adrenalectomy (ADX) using silver
      impregnation, and (ii) to investigate the CB-immunoreactivity in the hippocampus
      following 3 weeks corticosterone treatment. 24 h following ADX no degenerative
      changes, nor alterations in CB-immunoreactivity were found in the hippocampus.
      Both 3 and 21 days following ADX neurodegeneration in the dentate gyrus could be
      observed which was accompanied with a loss of CB-immunoreactive (CB-ir) cells in
      that parts of the dentate gyrus suffering neuronal degeneration. Additionally we
      observed a marked loss of CB-ir in the CA1 area both 3 and 21 days following ADX.
      Three weeks daily corticosterone treatment (10 mg/day) induced a marked increase
      of CB-ir exclusively in the CA1 pyramidal cell layer. We conclude that (i) there
      is a close relationship between the loss of CB-immunoreactive cells in the DG and
      the neuronal degeneration in the dentate gyrus following ADX, and (ii)
      corticosterone appears to be involved in the regulation of calbindin-D28k in the
      CA1 pyramidal cell layer.

PMID- 8574692
TI  - Carbohydrates and glycoconjugates.

PMID- 8574691
TI  - Dual regulation by mu, delta and kappa opioid receptor agonists of K+ conductance
      of DRG neurons and neuroblastoma X DRG neuron hybrid F11 cells.
AB  - The effects of the mu opioid receptor agonists, morphine and Tyr-D-Ala-Gly-N
      methyl-Phe-Gly-ol (DAGO), the delta opioid receptor agonist, Tyr-D-Pen-Gly-Phe-D
      penicillamine (DPDPE) and the kappa-opioid receptor agonist, dynorphin A-(1-13)
      on the whole-cell K+ currents (IK) of cultured mouse DRG neurons and
      neuroblastoma X DRG neuron hybrid F11 cells were studied. These opioid ligands
      all elicited dual effects. Low concentrations (< nM) usually elicited a transient
      increase in IK (within 1 min), followed by a sustained decrease in IK. In
      contrast, microM concentrations rapidly elicited a sustained increase in IK.
      After brief treatment with cholera toxin subunit B (CTX-B), the usual sustained
      decrease in IK evoked by < nM opioid agonists no longer occurred. Low
      concentrations then elicited only a sustained increase in IK. On the other hand,
      after chronic treatment with pertussis toxin (PTX), the usual microM opioid
      induced increases in IK no longer occurred and more than half of the cells
      responded with a sustained decrease of IK to microM as well as nM opioids. The
      results suggest that mu, delta and kappa opioid receptors are each coupled to K+
      channels through CTX-B- and PTX-sensitive transduction systems. Both systems have
      similar threshold concentrations to opioids. Activation of the CTX-B-sensitive
      opioid receptor/transduction system resulted in a decrease in K+ conductance of
      the cell which is generally associated with an increase in neuronal excitability.
      Activation of the other system resulted in an increase in K+ conductance which
      will, in general, decrease neuronal excitability. The net change in the IK
      depends upon which effect predominates. The dominance at different opioid
      concentrations may depend on the relative efficacies of the coupling of these two
      systems to K+ channels.

PMID- 8574693
TI  - Three-dimensional structures of oligosaccharides.
AB  - Oligosaccharides represent a particularly challenging class of molecules for
      conformational analysis. Recent advances in experimental and theoretical methods
      have begun to yield further insight into their conformational behavior; however,
      general rules governing their conformational preferences have not yet emerged. X
      ray and NMR techniques may provide vital insights into protein-bound
      oligosaccharide conformations, but these do not necessarily represent highly
      populated solution conformations. Moreover, an oligosaccharide's inherent
      flexibility and lack of strong intermolecular interactions places extreme demands
      on theoretical methods.

PMID- 8574694
TI  - Neoglycoconjugates and their applications in glycobiology.
AB  - Within the past two years new developments in neoglycoconjugate formation have
      increased the accessibility and usefulness of these probes for the analyses of
      glycan structure and function. This article reviews several simple chemical and
      enzymatic methods for tagging oligosaccharides with chromophores, biotin,
      peptides, proteins and lipids, and describes some representative applications of
      these neoglycoconjugates.

PMID- 8574695
TI  - Glycosylation inhibitors in biology and medicine.
AB  - Glycosidase inhibitors are moving increasingly out of the laboratory and into the
      clinic as potential agents for the treatment of diseases including diabetes, AIDS
      and cancer. These compounds, originally isolated from natural sources and
      utilized for unraveling the glycosylation pathways involved in post-translational
      modification of glycoproteins, have multiple effects that are only now being
      fully appreciated. In addition to their ability to inhibit processing
      exoglycosidases, lysosomal glycosidases and the intestinal disaccharidases
      involved in carbohydrate digestion, these compounds appear to have additional
      activities, including immunomodulatory properties and inhibition of glycolipid
      synthesis, which continue to expand their range of potential uses.

PMID- 8574696
TI  - Increasing diversity of animal lectin structures.
AB  - The number of animal proteins known to recognize carbohydrates and the number of
      their biological roles continue to increase. Comparisons of primary structures
      show that some of the newly described lectins are akin to previously investigated
      lectins, whereas others represent new structural groups. Progress has been made
      in understanding structure-function relationships for several lectins in both the
      old and the new categories.

PMID- 8574697
TI  - X-ray crystal structures of animal lectins.
AB  - Several important advances in the structure determination of animal lectins were
      made in the past year. The X-ray crystal structures of trimeric fragments of the
      human and rat mannose-binding proteins have defined for the first time the three
      dimensional subunit organization of a multimeric C-type lectin. In addition, the
      structure of a galectin-biantennary oligosaccharide complex has provided a model
      for what might be biochemically relevant cross-linking interactions. Finally, in
      a novel variation on lectin cross-linking, independent carbohydrate-binding sites
      on basic fibroblast growth factor have been found to recognize opposing faces of
      a synthetic heparin/heparan sulphate fragment, leading to growth-factor
      polymerization.

PMID- 8574698
TI  - Microbial recognition of target-cell glycoconjugates.
AB  - Attachment of microbial protein to host cell-surface carbohydrate is considered
      essential for successful infection. Information of conceptual interest, including
      crystal structures of protein-saccharide complexes and convincing models of
      target membrane penetration, continues to emerge for viruses and bacterial
      toxins. Other important data relate to therapeutic receptor blockade, through the
      use of saccharide analogs or vaccines directed against the microbial adhesin.

PMID- 8574699
TI  - Epitaxial growth of protein crystals from two-dimensional crystals on lipid
      layers.
AB  - Two-dimensional crystals of proteins formed on lipid layers effectively nucleate
      the epitaxial growth of three-dimensional protein crystals. Crystals suitable for
      X-ray crystallography can be grown in this way more rapidly, and using
      substantially lower concentrations of protein and precipitants, than when using
      conventional methods.

PMID- 8574700
TI  - Crystallization and structure determination of RNA.
AB  - Progress in the synthesis, purification and crystallization of RNA has resulted
      in the determination of several X-ray crystal structures of RNA molecules over
      the past few years. Methods proven and under development will lead to future
      structure determinations and shed light on the structural basis for RNA's many
      functions.

PMID- 8574701
TI  - Ab initio phase determination and phase extension using non-crystallographic
      symmetry.
AB  - Non-crystallographic symmetry (NCS) can be used to improve, extend or find ab
      initio phases to be associated with a set of observed structure amplitudes,
      resulting in an interpretable electron-density map. The simplest application is
      merely to improve the accuracy of the phases by cyclically averaging the electron
      density, Fourier back-transformation of the modified map, and recomputing a new
      map with the newly found phases. The first sophistication of this procedure is to
      phase extend, in successive small steps, the currently available phase
      information to higher resolution, where only observed amplitudes were previously
      available. A further sophistication is to initiate the phase extension from very
      low resolution where a simple geometric model, or an electron microscope image,
      would be consistent with the chosen resolution. A number of recent examples of
      virus structure determination exist where such ab initio phasing was successful.
      The ultimate ab initio phase determination would be to extend phases given only
      an estimate of the F(000) term.

PMID- 8574702
TI  - Freeze trapping of reaction intermediates.
AB  - Structural intermediates in a biological reaction may be monitored by rapid
      spectroscopic or somewhat slower structural techniques. Intermediates may evolve
      in real time (no trapping), be stabilized by chemical manipulation of the
      reactants, the macromolecule or the solvent (chemical trapping), or be stabilized
      by lowering the temperature (freeze trapping). The last is beginning to be
      coupled with X-ray diffraction, electron cryomicroscopy and solid-state NMR
      approaches to characterize the trapped intermediates. Care in conducting such
      experiments, together with an awareness of possible artefacts, is essential if
      reliable structural results are to be obtained.

PMID- 8574703
TI  - Automated analysis of nuclear magnetic resonance assignments for proteins.
AB  - Recent developments in protein NMR technology provide spectral data that are
      highly amendable to analysis by computer software systems. Automated methods of
      analysis use constraint satisfaction, pseudoenergy minimization, directed search,
      neural net, simulated annealing, and/or genetic algorithms to establish
      sequential links and sequence-specific assignments. The most advanced systems
      provide automated analysis of complete backbone and extensive side-chain
      resonance assignments for proteins of 50-150 amino acids.

PMID- 8574704
TI  - Field gradient techniques in NMR spectroscopy.
AB  - In recent years NMR spectroscopy has emerged as a powerful technique for studying
      the structure and dynamics of biomolecules in solution. The development of
      shielded pulsed-field gradient coils for high-resolution NMR spectroscopy has led
      to significant improvements in a large number of experiments which are used to
      provide such information. Experiments enhanced with pulsed-field gradients have
      fewer artifacts, suffer far less from problems of solvent suppression and have
      reduced phase cycles relative to their non-gradient counterparts. The whole array
      of NMR experiments available for macromolecular structure determination is likely
      to benefit substantially from the incorporation of gradient pulses.

PMID- 8574705
TI  - Calorimetry of proteins and nucleic acids.
AB  - The availability of sensitive calorimetric instrumentation has led to a
      considerable increase in thermodynamic studies of proteins, nucleic acids, and
      their interactions. This article reviews some of the recent contributions of
      calorimetry to characterizing the thermodynamic origins of protein and nucleic
      acid stability and conformational preferences, as well as the interactions of
      proteins with each other, with small molecules, and with nucleic acids.

PMID- 8574706
TI  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS).
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been
      responsible for solving many problems in structural biology. Mass analysis is now
      used routinely to confirm proper expression and processing of proteins, and to
      locate and identify post-translational modifications. Innovative advances in
      instrumentation have led to higher mass resolution and mass accuracy. New sample
      preparation methods are likewise yielding higher sensitivity plus greater
      tolerance for buffer components that have in the past suppressed signals at
      higher concentrations. Advancements in the technique have also led to new or
      improved applications in many areas, including peptide sequencing and the
      identification of proteins by database searching with peptide masses. Instruments
      with lower cost, smaller size, and higher performance are making mass
      measurements available to an increasing number of laboratories. MALDI-MS is
      poised to continue to improve in performance and in its usefulness for current
      and new applications.

PMID- 8574708
TI  - Carbohydrates and glycoconjugates.

PMID- 8574707
TI  - Surface plasmon resonance and its use in biomolecular interaction analysis (BIA).
AB  - Since the advent of surface plasmon resonance (SPR)-based interaction analysis
      techniques in 1990 the field has grown rapidly. So far, more than 220
      publications and hundreds of laboratories have reported useful applications for
      this label-free real-time binding approach. Milestones passed during the past
      year include the direct detection of low molecular mass (200 Da) binding events
      and applications in several new fields as disparate as chaperonins, cellular
      adhesion, molecular biology, transcription and small-molecule screening.

PMID- 8574709
TI  - Biophysical methods.

PMID- 8574710
TI  - Endoscopic intubation of oesophagogastric malignancy.

PMID- 8574711
TI  - Combination of ranitidine and cisapride in the treatment of reflux oesophagitis.
AB  - OBJECTIVE: To compare the efficacy of treatment for 8 or 12 weeks with a
      combination of 150 mg ranitidine twice daily plus 20 mg cisapride twice daily
      with ranitidine 150 mg twice daily alone in patients with moderate-to-severe
      reflux oesophagitis. DESIGN: A double-blind, randomized, parallel-group clinical
      trial. SETTING: Forty-two out-patient centres in the UK, Germany, Ireland,
      Denmark and South Africa. PATIENTS: A total of 344 symptomatic patients with
      endoscopically confirmed reflux oesophagitis (Hetzel grade 3 or 4) were randomly
      assigned to receive the study medication. INTERVENTIONS: Patients underwent a
      follow-up endoscopy after 8 weeks' treatment. Healing was defined as Hetzel grade
      0 or 1 upon endoscopy. Patients with unhealed oesophagitis continued their
      allocated treatment regimen for a further 4 weeks before undergoing a repeat
      endoscopy. MAIN OUTCOME MEASURES: The primary efficacy analysis was based on a
      comparison of 12-week cumulative healing rates between the two groups. RESULTS: A
      statistically significant difference (P = 0.015) in the cumulative healing rate
      was observed between patients given ranitidine plus cisapride (82%) and those
      given ranitidine alone (71%). Oesophagitis in patients who received the
      combination was twice as likely to heal as that in patients who received
      ranitidine alone. CONCLUSION: A combination of 150 mg ranitidine twice daily and
      20 mg cisapride twice daily is a safe and effective treatment for moderate-to
      severe reflux oesophagitis and offers increased efficacy over ranitidine alone.

PMID- 8574712
TI  - Preventive effects of recombinant human epidermal growth factor on the
      oesophageal epithelium in pigs subjected to sclerotherapy.
AB  - OBJECTIVE: To investigate the role of epidermal growth factor (EGF), a small
      (relative molecular mass 6000) polypeptide with mitogenic properties in the
      protection of gastrointestinal mucosal integrity. DESIGN: A prospective,
      randomized and blinded study. METHODS: Twenty-four minipigs with surgically
      induced portal hypertension underwent four consecutive weekly sessions of
      oesophageal sclerotherapy with 5 ml 1% polidocanol and were concomitantly treated
      with either a placebo or human recombinant EGF administered subcutaneously.
      Mucosal damage was evaluated on a weekly basis by endoscopic estimation of the
      size of the ulcerated area and by post-mortem morphometry. The EGF-induced
      morphological changes in the oesophageal epithelium were also evaluated
      histologically. RESULTS: In sclerosed and non-sclerosed parts of the oesophagus
      EGF significantly increased the thickness of the oesophageal epithelium (P <
      0.03), but failed to reduce significantly the degree of oesophageal damage
      associated with sclerotherapy (P = 0.11). CONCLUSIONS: Systemic EGF treatment
      induces proliferation of the oesophageal mucosa, and EGF may therefore have the
      potential to reduce sclerotherapy-induced oesophageal damage.

PMID- 8574713
TI  - Non-ulcer dyspepsia in the long-term perspective.
AB  - OBJECTIVE: To study the natural history of non-ulcer dyspepsia. DESIGN:
      Retrospective study on consecutive cases of non-ulcer dyspepsia diagnosed in 1980
      and 1981. The long-term course was ascertained from medical records and from
      answers to a questionnaire completed by the patients at 10-year follow-up.
      SETTING: Out-patients at the endoscopy unit of a county hospital. PATIENTS: The
      diagnosis was based on typical symptoms of dyspepsia, a normal index endoscopy
      and a lack of evidence of organic disease related to the symptoms during the
      subsequent 12-month period. Two hundred and seventy-one patients were entered
      into the study. Of the 195 who received a questionnaire at 10-year follow-up, 165
      (85%) responded. RESULTS: The median age at inclusion was 51 years (25-75
      percentiles 38-65 years), and 130 men and 141 women were included in the study.
      The cumulative death rate after 10 years was 18%, a value no greater than that in
      the general population: 8% had died of cardiovascular disease, 1.5% of
      gastrointestinal cancer and 3% of other malignancies. One patient had died of a
      perforated gastric ulcer. At 10-year follow-up, a further three patients had
      developed peptic ulcers (expected number 4.2), 64% had experienced dyspeptic
      symptoms during the preceding 12 months and 41% had been taking analgesics during
      the previous week. Of the symptoms listed by the patients, 30% were typical of
      irritable bowel syndrome. CONCLUSION: Non-organic dyspepsia seems to be a chronic
      disease in most patients. The course is benign and unrelated to peptic ulcer
      disease.

PMID- 8574714
TI  - Efficacy and optimum dose of omeprazole in a new 1-week triple therapy regimen to
      eradicate Helicobacter pylori.
AB  - OBJECTIVE: To assess the efficacy of a 1-week course of omeprazole,
      clarithromycin and tinidazole for the eradication of Helicobacter pylori and the
      optimum dose of omeprazole required. DESIGN: The study was divided into two
      sequential phases. The first phase was an open, two-centre study. The second
      phase was a single-blind, single-centre study. METHODS: Patients found to be
      infected with H. pylori at endoscopy were enrolled in the study. In phase 1,
      patients were prescribed 20 mg omeprazole, 250 mg clarithromycin and 500 mg
      tinidazole twice daily for 1 week. In phase 2, all patients were prescribed 250
      mg clarithromycin and 500 mg tinidazole twice daily for 1 week. In addition,
      patients were randomly assigned to receive 20 mg omeprazole twice daily (group
      A), 20 mg omeprazole daily (group B) or no omeprazole (group C). Eradication was
      assessed in all patients by 13C-urea breath testing 4 weeks after the completion
      of therapy. RESULTS: In phase 1, H. pylori eradication was achieved in 132 (88%)
      of 150 evaluable patients. In phase 2, eradication was achieved in 44 (88%) of 50
      individuals in group A, 47 (88.7%) of 53 in group B and 30 (63.8%) of 47 in group
      C. In the omeprazole groups, 22 patients harboured metronidazole-resistant
      strains of H. pylori and all were cured by the omeprazole regimen. One patient
      harboured a strain of H. pylori that was resistant to clarithromycin alone but
      which was successfully eradicated. Treatment failed in two out of three patients
      harbouring H. pylori strains resistant to both clarithromycin and tinidazole.
      CONCLUSION: One week of omeprazole, clarithromycin and tinidazole is effective in
      eradicating H. pylori. There is no advantage in increasing the dose of omeprazole
      from once to twice daily. This regimen is effective in patients with 5
      nitroimidazole-resistant strains of H. pylori.

PMID- 8574715
TI  - Antibiotic prophylaxis for ERCP: a randomized clinical trial comparing
      ciprofloxacin and cefuroxime in 200 patients at high risk of cholangitis.
AB  - OBJECTIVE: To compare the efficacy and safety of oral ciprofloxacin and
      intravenous cefuroxime in patients at high risk of cholangitis after endoscopic
      retrograde cholangiopancreatography (ERCP). DESIGN: Prospective, randomized
      study. SETTING: A primary and tertiary referral centre. PATIENTS: A series of 232
      consecutive patients who either had radiological evidence of biliary obstruction
      or were aged over 70 years were randomly assigned to receive either oral
      ciprofloxacin or intravenous cefuroxime before and after ERCP. Two-hundred and
      nine patients finished the study, with 23 being excluded because of withdrawal of
      consent or incomplete ERCP. INTERVENTIONS: Patients underwent ERCP: blood samples
      were taken for culture, full blood count and biochemistry before and after the
      procedure. Clinical follow-up was carried out 7 and 42 days after ERCP. MAIN
      OUTCOME MEASURES: Clinical, bacteriological or biochemical evidence of
      cholangitis, septicaemia or adverse drug reactions, and the cost of both
      protocols. RESULTS: Follow-up was recorded in all 209 patients who completed the
      study. By 42 days after ERCP, three patients had died (cholangiocancer,
      pancreatic cancer and renal failure). Cholangitis was diagnosed in one patient
      from each of the two trial groups. Blood cultures from the patient on
      ciprofloxacin gave negative results, but a post-ERCP blood sample from the
      patient on cefuroxime grew Pseudomonas aeruginosa, which was sensitive to
      ciprofloxacin. There were no serious side-effects in either study group, but two
      patients assigned to ciprofloxacin became too nauseous to take the medication.
      The cost of the cefuroxime protocol was l7.56 pounds per patient, compared with
      4.76 pounds per patient for the ciprofloxacin protocol. CONCLUSION: A pre- and
      post-ERCP oral ciprofloxacin regime is safe and provides effective prophylaxis
      against ERCP-induced cholangitis and septicaemia in high-risk patients. It is
      also more economical than a regime of intravenous cefuroxime and does not require
      nursing staff with training in intravenous techniques.

PMID- 8574716
TI  - Alpha-1-antichymotrypsin is an effective inhibitor of pancreatitis-induced lung
      injury.
AB  - BACKGROUND: Pancreatitis-induced adult respiratory distress syndrome (ARDS) may
      result from an imbalance between leucocyte proteases, produced by infiltrating
      neutrophils, and endogenous protease inhibitors. OBJECTIVE: The aim of this study
      was to evaluate the role of recombinant alpha-1-antichymotrypsin (rACT P3-P3'),
      an endogenous serine protease inhibitor, in ameliorating lung injury associated
      with pancreatitis. DESIGN: Sprague-Dawley rats were randomly divided into control
      (saline infusion) and pancreatitis groups, which were treated immediately with
      saline or rACT P3-P3' (50 mg/kg body weight). METHODS: Myeloperoxidase (MPO) was
      employed as a monitor of neutrophil traffic in the lung, and wet-dry lung weights
      as a measure of pulmonary endothelial permeability. Lungs were also evaluated
      histologically. RESULTS: Caerulein (5 micrograms/kg body weight/h) induced
      pancreatitis in all animals, with an increase in serum amylase from 1851 +/- 208
      IU (control) to 5198 +/- 924 IU (pancreatitis), P < 0.05. Pancreatitis caused a
      significant increase in MPO activity (7.8 +/- 1.1 units compared with 2.08 +/-
      0.5 units in controls, P < 0.001) and wet-dry lung weight ratios (12.8 +/- 3.3
      compared with 3.2 +/- 0.1 in controls, P < 0.001), indicating significant
      pulmonary neutrophil influx and microvascular leakage, respectively. These
      increases in MPO activity and wet-dry ratios were decreased in the pancreatitis
      group treated with rACT P3-P3' (MPO 4.68 +/- 0.7 units, wet-dry ratio 4.2 +/-
      0.5, P < 0.05 compared with the untreated pancreatitis group). CONCLUSION: These
      data support the hypothesis that deficient endogenous protease inhibition may be
      responsible for the neutrophil-mediated lung injury observed in pancreatitis and
      suggest that there may be a therapeutic role for recombinant protease inhibitors
      such as alpha-1 antichymotrypsin.

PMID- 8574717
TI  - Disease-related worries and concerns: a study on out-patients with inflammatory
      bowel disease.
AB  - OBJECTIVE: To investigate the relationship between inflammatory bowel disease
      (IBD) patients' disease-related worries and concerns and their disease-related
      data, sociodemographic variables and perceived information level with respect to
      IBD. STUDY DESIGN: Prospective evaluation of disease-related concerns. SETTING:
      Out-patient IBD clinic of a university hospital. STUDY POPULATION: The study
      included 105 patients with IBD (72 with Crohn's disease and 33 with ulcerative
      colitis). MEASUREMENTS: Worries and concerns were measured using the standardized
      25-item rating form of IBD patient concerns; actual disease activity was assessed
      by physicians using the Crohn's disease and clinical activity indices.
      Sociodemographic and other disease-related data were collected using a structured
      questionnaire. Patients' perceived information level was measured using a visual
      analogue scale. RESULTS: The issues of greatest concern to our patients were, in
      descending order of importance, having an ostomy bag (mean score +/- SD 63.6 +/-
      38), the effects of medication (53.1 +/- 34), having surgery (51.6 +/- 36), the
      uncertain nature of the disease (46.5 +/- 32) and energy level (41.5 +/- 34).
      Patients with ulcerative colitis scored higher with respect to concern about loss
      of bowel control (P < 0.03). Disease-related worries and concerns correlated
      poorly with disease-related data (actual disease activity, severity of the course
      of IBD, diagnosis, disease duration or location, medication) but showed a
      significant negative correlation with patients' perceived information level about
      IBD (t = 0.2, P < 0.004). Lower information-level scores were associated with
      greater concerns. CONCLUSION: We conclude that the patients' information level
      about IBD and disease-related concerns have to be considered in clinical
      practice. Better information about IBD and psychosomatic counselling for patients
      who show high levels of concern may improve their quality of life and clinical
      care.

PMID- 8574718
TI  - Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease: do they
      recognize different subsets of a heterogeneous disease?
AB  - OBJECTIVE: To evaluate the prevalence of anti-neutrophil cytoplasmic antibodies
      in a series of patients with inflammatory bowel disease, the discriminatory value
      of these antibodies in differentiating between ulcerative colitis and Crohn's
      disease, their antigen specificity and their correlation with epidemiological and
      clinical variables. METHODS: Serum anti-neutrophil cytoplasmic antibodies were
      evaluated by indirect immunofluorescence and immunoblotting using neutrophils
      isolated from peripheral blood and by enzyme-linked immunosorbent assays (ELISAs)
      using proteinase 3 and myeloperoxidase as antigens. RESULTS: Anti-neutrophil
      cytoplasmic antibodies were detected by immunofluorescence in 43 (39.8%) of 108
      patients with ulcerative colitis, in 11 (11.9%) of 92 patients with Crohn's
      disease (P < 0.001) and 5 (6.8%) of 73 control patients. The predominant pattern
      was perinuclear staining around neutrophil nuclei (44 of 59, 75%); a homogeneous
      cytoplasmic staining was present in 15 (25%) of 59 sera, mainly among Crohn's
      disease and control patients. The ELISAs gave no positive results. Recognition of
      proteins of relative molecular masses 27,000 and 49,000 at immunoblotting was
      common to ulcerative colitis, Crohn's disease and control sera. The proteins of
      relative molecular masses 32,000 and 106,000 were recognized exclusively by 11%
      of anti-neutrophil-positive ulcerative colitis sera. No significant correlation
      was found between the presence of anti-neutrophil cytoplasmic antibodies and the
      demographic and clinical characteristics of the patients. CONCLUSION: Anti
      neutrophil cytoplasmic antibodies are detectable in a large proportion of
      patients with ulcerative colitis, but their prevalence in a limited proportion of
      patients with Crohn's disease reduces their discriminatory capability. The
      persistence of anti-neutrophil cytoplasmic antibodies after total colectomy and
      the absence of a correlation between the activity of the disease and the presence
      or titre of these antibodies support the hypothesis that anti-neutrophil
      cytoplasmic antibodies are not simply an epiphenomenon of colonic inflammation.

PMID- 8574719
TI  - Arachidonic acid metabolism and intracellular calcium concentration in
      inflammatory bowel disease.
AB  - OBJECTIVE: To study the alteration of prostaglandin E2 (PGE2) and leukotriene B4
      (LTB4) synthesis and intracellular Ca2+ concentration in chronic inflammatory
      bowel disease, and to ascertain the effect of anti-inflammatory drugs and other
      mediators on eicosanoid synthesis and Ca2+ concentration. METHODS: Biopsies taken
      from the descending colon were isolated biochemically. The suspension of isolated
      mucosal cells was incubated for 15 min in the presence and absence of arachidonic
      acid and the Ca2+ ionophore A23187. PGE2 and LTB4 concentrations in the
      incubation medium were measured by radioimmunoassay, and the intracellular Ca2+
      concentration was determined using fura-2. We studied 107 subjects. In addition,
      the effects of bradykinin, endothelin, cyclosporin A and PGE2 on intracellular
      Ca2+ concentration were determined in 25 individuals. RESULTS: Untreated patients
      with active inflammatory bowel disease showed a significant increase in LTB4
      synthesis compared with healthy controls. However, in patients receiving
      steroids, sulphasalazine or 5-aminosalicylic acid, both LTB4 and PGE2 synthesis
      were markedly decreased. When arachidonic acid was added to the cell suspension,
      it significantly stimulated LTB4 synthesis, especially in patients with active
      disease. Patients with active Crohn's disease or ulcerative colitis had
      moderately higher Ca2+ levels than healthy controls. However, there was a
      significant decrease in intracellular Ca2+ concentration in patients with
      quiescent disease who were receiving maintenance therapy. CONCLUSION: We suggest
      that increased LTB4 synthesis and elevated intracellular Ca2+ concentrations
      contribute to the pathophysiology of inflammatory bowel disease. Drugs effective
      in the treatment of these diseases may exert their pharmacological action by
      normalizing these pathological findings.

PMID- 8574720
TI  - Treatment of travellers' diarrhoea: zaldaride compared with loperamide and
      placebo.
AB  - OBJECTIVE: To compare zaldaride maleate, a calmodulin inhibitor with
      gastrointestinal antisecretory properties, with loperamide and a placebo in the
      treatment of travellers' diarrhoea. DESIGN: Randomized, double-blind, double
      dummy study. SETTING: Study clinic staffed by European residents on Nile cruise
      ships. PATIENTS: Tourists (n = 436) who acquired travellers' diarrhoea during the
      Nile cruise. INTERVENTIONS: (1) Zaldaride 20 mg four times daily, (2) zaldaride 2
      x 20 mg as initial loading dose followed by three doses of 20 mg on the first day
      and four doses of 20 mg on the second day, (3) loperamide 2 x 2 mg loading dose
      following by a flexible dosage of 2 mg after each unformed stool (maximum of 16
      mg daily), (4) placebo. MAIN OUTCOME MEASURES: Number of unformed stools, rate of
      improvement of patients with diarrhoea, rate of relief from diarrhoea. RESULTS:
      Among the 331 compliant and fully evaluated patients, the zaldaride with loading
      dose group showed no significant differences in cure rates from the loperamide
      group. For most parameters, zaldaride without a loading dose and the placebo
      resulted in significantly lower cure rates. CONCLUSIONS: A zaldaride regimen
      including a loading dose was shown to be well tolerated and as effective as
      loperamide.

PMID- 8574721
TI  - The effect of barium sulphate on small bowel motility in man.
AB  - OBJECTIVE: To investigate the effect of barium sulphate on small bowel motor
      activity. METHODS: Nine healthy male volunteers underwent two separate,
      ambulatory 24 h manometry studies. Jejunal motor activity was recorded during
      fasting and after ingestion of 300 ml volumes of barium, water or a glucose
      solution (1380 kJ). Recordings were analysed visually for recurrence of phase III
      of the migrating motor complex, and a validated computer program was used to
      calculate the incidence and amplitude of contractions. RESULTS: Phase III
      reappeared 71 +/- 10 min after ingestion of barium sulphate. This interval was
      not significantly different after the intake of water (60 +/- 8 min) or in the
      fasted state (88 +/- 21 min), but it was significantly shorter than after
      ingestion of a glucose solution (136 +/- 17 min). The mean incidence of
      contractions after ingestion of barium was 3.0 +/- 0.5/min. This was
      significantly higher than that observed after water (1.9 +/- 0.4/min) and also
      significantly higher than during fasting (1.5 +/- 0.3/min), but not significantly
      different from the incidence of contractions after ingestion of a glucose
      solution (2.2 +/- 0.4/min). The mean amplitude of contractions after ingestion of
      barium was 24.2 +/- 1.4 mmHg. This was significantly higher than the amplitude of
      contractions during fasting (19.5 +/- 1.0 mmHg), but not significantly different
      from that after water intake (23.7 +/- 1.3 mmHg) or after ingestion of a glucose
      solution (21.4 +/- 1.3 mmHg). CONCLUSION: Small bowel motor activity after
      ingestion of barium sulphate differs distinctly both from the interdigestive and
      from the postprandial motor pattern. Barium suspensions do not interrupt the
      migrating motor complex with a typical 'fed' pattern, but contractions are more
      frequent after ingestion of barium than after the intake of water and are both
      more frequent and of greater force than the contractions observed during the
      fasted state.

PMID- 8574722
TI  - Effects of graded glutamine intake on liver protein metabolism following partial
      hepatectomy.
AB  - OBJECTIVE: To elucidate whether glutamine can influence the rate of regeneration
      and protein metabolism in regenerating liver. DESIGN: Liver regeneration rate,
      protein content and synthesis were measured in rats 7 days after a liver
      resection or sham operation. After the operation, the rats were fed three
      elementary isonitrogenous diets, one without and two including different levels
      of glutamine. METHODS: Fifty-six rats were randomly assigned to either sham
      operation or liver resection. After the operation, they received an
      isonitrogenous, isocaloric elementary diet with a glutamine content of 0, 2 or
      4%. The resected part of the liver was weighed and analysed for DNA and protein
      content. Seven days later, hepatic protein synthesis was measured by the flooding
      method using L-[3H]-phenylalanine, and the liver was analysed for DNA, RNA and
      protein content. RESULTS: The regeneration rate was higher in the group receiving
      2% glutamine but not in the group receiving 4% glutamine than in the 0% group.
      Total protein content was increased in regenerating liver in the 2 and 4%
      glutamine groups compared with the 0% group. Protein synthesis was higher 7 days
      after liver resection than in sham-operated rats. In the 2% group there was a
      tendency towards increased protein synthesis compared with the 0% group.
      CONCLUSION: A diet with normal glutamine content improved liver regeneration
      rate, total protein content and protein synthesis in regenerating liver, but an
      excess of glutamine did not enhance this effect.

PMID- 8574723
TI  - Systemic vascular resistance during high-volume plasmapheresis in patients with
      fulminant hepatic failure: relationship with oxygen consumption.
AB  - BACKGROUND: In patients with fulminant hepatic failure, systemic vascular
      resistance and blood pressure are often reduced. OBJECTIVE: To determine whether
      systemic vascular resistance increases during high-volume plasmapheresis, which
      is assumed to eliminate endogenous vasodilatory substances from the bloodstream.
      DESIGN: A prospective study. PATIENTS AND METHODS: Ten patients [median age 48
      (range 21-53) years] were admitted for liver transplantation. Systemic
      haemodynamic variables were determined using a catheter in a radial artery and a
      thermodilution catheter placed in a pulmonary artery. Ten (range 8-15) litres of
      fresh frozen plasma were exchanged, while body temperature [37.6 (range 36.6
      38.4) degrees C], blood partial pressure of carbon dioxide [3.75 (range 3.30
      4.50) kPa] and peak inspiratory ventilatory pressure [24 (range 20-26) mmHg] were
      kept constant. RESULTS: Mean arterial pressure increased from 74 (range 61-110)
      to 96 (range 68-103) mmHg and cardiac index decreased from 5.2 (range 3.6-7.5) to
      4.2 (range 3.4-6.6) l/min/m2. The systemic vascular resistance index increased
      from 662 (range 430-1270) to 1060 (range 621-1520) dyn s/cm5/m2. In contrast, the
      pulmonary vascular resistance index [42 (range 20-110) dyn s/cm5/m2) remained
      constant. As cardiac index decreased, oxygen delivery decreased from 939 (range
      680-1496) to 745 (range 601-1189) ml/min/m2 with no effect on oxygen consumption
      [171 (87-231) ml/min/m2], as the arteriovenous oxygen extraction ratio increased
      from 17 (range 9-22) to 25 (range 8-31)% (P < 0.02). CONCLUSION: In patients with
      fulminant hepatic failure, cardiac output, systemic vascular resistance and
      arterial blood pressure improved during high-volume plasmapheresis.

PMID- 8574724
TI  - Effects of propranolol compared with clonidine on portal haemodynamics: a double
      blind cross-over study using duplex-Doppler ultrasonography.
AB  - BACKGROUND: Patients with liver cirrhosis and large oesophageal varices run a
      high risk of digestive haemorrhage due to the rupture of oesophageal varices, an
      event associated with a high mortality. At present, the only treatment for the
      prevention of first bleeding from oesophageal varices on which there is general
      agreement is drug-based. In order to tailor drug treatment to the requirements of
      individual patients more precisely, an ever-increasing number of drugs is being
      investigated. DESIGN: Double-blind cross-over study. METHODS: Sixteen cirrhotic
      patients with large oesophageal varices were studied by means of duplex-Doppler
      ultrasonography to determine variations in portal haemodynamics after oral
      administration of 0.150 mg clonidine and to compare these with the variations
      observed after oral administration of 40 mg propranolol. RESULTS: Propranolol
      caused a significant reduction in maximum portal flow velocity (P < 0.001),
      whereas clonidine failed to cause any such variation (P = 0.194). Considering as
      responders those patients who exhibited at least a 10% decrease in maximum portal
      flow velocity, 11 patients responded to propranolol; of these, three also
      responded to clonidine. No patient responded only to clonidine. CONCLUSION: The
      absence of any effects on the parameters of portal haemodynamics would appear to
      deny clonidine any significant role in preventing first bleeding resulting from
      the rupture of oesophageal varices.

PMID- 8574725
TI  - Genome detection in liver and peripheral blood mononuclear cells: predictor
      factors of sustained response in patients with chronic hepatitis C.
AB  - BACKGROUND: In chronic hepatitis C, relapses of liver disease occur in as many as
      50% of patients responding to interferon (IFN) therapy. Although the presence of
      serum hepatitis C virus (HCV) RNA at the end of therapy predicts a relapse, its
      absence is not a reliable indicator of cure. In this study we have determined
      whether responders to IFN (normalization of liver chemistry and clearance of
      serum HCV-RNA) harbour HCV-RNA in the liver and peripheral blood mononuclear
      cells (PBMCs), and whether finding the genome at these sites has prognostic
      significance. METHODS: After the conclusion of therapy, we tested for HCV-RNA in
      the liver of all the patients (anti-HCV-positive): 16 complete responders with
      normalization of liver chemistry and clearance of serum HCV-RNA and five non
      responders. In 13 of the 16 complete responders we also tested for HCV-RNA in
      PBMCs. Patients were followed up for 9 months. RESULTS: Liver HCV-RNA was
      detected in each of the five non-responders and in four of the 16 complete
      responders (25%). The viral genome was detected in the PBMCs of six complete
      responders (46%). During follow-up a relapse of hepatitis C occurred in the 10
      complete responders with liver or PBMC HCV-RNA but in only one (16%) of the six
      complete responders without HCV-RNA in liver or PBMCs. CONCLUSION: Reliable
      information on the prognosis of chronic hepatitis C responders can only be
      obtained by testing for HCV-RNA in serum, liver and PBMCs at the end of therapy.
      Patients with HCV-RNA at any of these sites stand a high risk of disease relapse.
      The risk is low but not abolished in patients without detectable HCV-RNA.

PMID- 8574726
TI  - Hepatic granulomatosis in a patient with Graves' disease.
AB  - We report a case of granulomatous hepatitis in a patient with hyperthyroidism
      resulting from Graves' disease. A 30-year-old man presented with massive weight
      loss, jaundice, tachyarrhythmia and goitre. Liver function tests showed mild
      cytolysis and cholestasis and massive hyperbilirubinaemia. The echogram of liver
      and bile ducts was normal and no infection was found. A liver biopsy revealed a
      mixed cytolytic and cholestatic hepatitis with intralobular epithelioid
      granulomas. No specific cause was identified, and sarcoidosis and primary biliary
      cirrhosis were ruled out. The outcome was favourable with antithyroid therapy and
      short-term glucocorticoid therapy, and the patient was totally free of symptoms
      after 2 years. To our knowledge, this is the first case of granulomatous
      hepatitis to be reported in association with Graves' disease. The clinical
      evolution of the liver disease paralleled the evolution of hyperthyroidism.

PMID- 8574727
TI  - Proceedings of the 7th International Symposium on Helicobacter pylori and its
      Diseases. Tokyo, Japan, 18-19 April 1994.

PMID- 8574729
TI  - Helicobacter pylori infection and chronological extension of atrophic gastritis.
AB  - OBJECTIVES: To determine the relationship between Helicobacter pylori infection
      and chronological extension of atrophic gastritis. PATIENTS AND METHODS: We
      studied 137 non-ulcer patients. The extent of atrophic gastritis was assessed
      endoscopically and scored on a scale of 1-6 (endoscopic score) using the atrophic
      pattern system. H. pylori infection was assessed by enzyme-linked immunosorbent
      assay with serum anti-H. pylori immunoglobulin G. The correlation between patient
      age and endoscopic score was determined for H. pylori-positive and -negative
      patients. RESULTS: A positive correlation between age and extent of atrophic
      gastritis was found in both H. pylori-positive and -negative patients. In groups
      of patients aged 20-29 and 30-39 years, those with H. pylori had more extensive
      atrophic gastritis than those without H. pylori. CONCLUSIONS: Chronological
      extension of atrophic gastritis was found in patients with and without H. pylori
      infection.

PMID- 8574728
TI  - Vaccine strategies for prevention of Helicobacter pylori infection.
AB  - OBJECTIVE: To examine the level and duration of the humoral immune response to
      Helicobacter felis following oral immunization or infection. DESIGN AND METHODS:
      Germ-free mice were orally immunized with sonicated H. felis plus cholera toxin
      five times over 6 weeks. One week after immunization was completed, immunized and
      control non-immunized mice received an oral challenge of live H. felis organisms.
      The animals were killed at 3-week intervals and serum, gastric washings,
      intestinal washings and gastric biopsies were obtained. H. felis infection was
      confirmed by a positive urease test or culture of the gastric biopsy. Serum
      gastric and intestinal antibody titers were determined by enzyme-linked
      immunosorbent assay. CONCLUSION: Infection and immunization against H. felis
      produces a specific humoral response. The humoral response in infection alone is
      significantly smaller than that of immunized animals until 6 weeks after
      infection. The humoral response following oral immunization persists for at least
      18 weeks without further stimulation. The presence of an H. felis-specific
      antibody immune response before infection may be needed to protect animals from
      acute Helicobacter infection.

PMID- 8574730
TI  - Helicobacter pylori, gastric cancer and gastric epithelial kinetics: a review.
AB  - AIM: To review the evidence that Helicobacter pylori promotes gastric
      carcinogenesis, with particular reference to gastric epithelial proliferation.
      MATERIALS AND METHODS: Gastric epithelial kinetics were reviewed and a series of
      studies of gastric mucosal proliferation in H. pylori-associated gastritis were
      performed in the intact and postsurgical stomach. In vitro bromodeoxyuridine
      labelling was performed on endoscopic antral biopsies from subjects with a normal
      gastric mucosa, with H. pylori-negative gastritis and with H. pylori-positive
      gastritis. The effect of eradication therapy was assessed. Corpus biopsies from
      the intact stomach were also examined and compared to body-type biopsies from the
      postsurgical stomach. RESULTS: Cell proliferation was increased in patients with
      H. pylori-positive gastritis and returned to normal levels following eradication
      therapy. The presence of H. pylori in the postsurgical stomach had a synergistic
      effect on gastric epithelial proliferation. CONCLUSIONS: H. pylori may promote
      gastric carcinogenesis by increasing epithelial proliferation. H. pylori and bile
      appear to have a synergistic effect on gastric cell proliferation.

PMID- 8574731
TI  - Helicobacter pylori as a promoter of intestinal metaplasia and gastric cancer: an
      alluring hypothesis in search of evidence.
AB  - OBJECTIVES: To examine the current evidence supporting a role for Helicobacter
      pylori in the genesis of intestinal metaplasia and to offer suggestions for the
      design of studies that could be carried out to elucidate the pathogenesis of
      gastric cancer. METHOD: Literature review. CONCLUSIONS: The epidemiologic
      relationship between H. pylori and gastric cancer is widely accepted; however,
      the sequence of events leading to the development of carcinoma is unknown. A
      currently accepted model is that chronic active gastritis progresses to atrophic
      gastritis with intestinal metaplasia, dysplasia and eventually neoplasia. The
      relationship between H. pylori and intestinal metaplasia remains unclear, as
      several studies have yielded conflicting results.

PMID- 8574732
TI  - Evaluation of a new bismuth-free triple therapy in nude mice and humans.
AB  - OBJECTIVES: To evaluate the efficacy of a new triple therapy (amoxycillin,
      metronidazole, plaunotol) in eradicating Helicobacter pylori in a nude mouse
      model and in humans. MATERIALS AND METHODS: In an animal study we used 215 nude
      mice infected with H. pylori to assess the ability of single, dual and triple
      therapy to eradicate H. pylori from the mouse stomach. The number of H. pylori in
      the mouse stomach and extent of the gastritis was assessed from 1 to 4 weeks
      after treatment. In a human study, we enrolled 78 H. pylori-positive patients
      with recurrent peptic ulcer diseases, 29 of whom were given triple therapy
      (amoxycillin and metronidazole for 1 week and plaunotol for 4 weeks). Patients in
      the control group (n = 49) were given a histamine H2-receptor antagonist. All
      patients were assessed 5 and 11 months after completion of therapy. RESULTS: In
      the mouse model, both the number of H. pylori and the gastritis score were
      significantly lower in the triple therapy group than in any other treatment group
      assessed 1-4 weeks after completion of therapy. In the human study, the triple
      therapy eradicated H. pylori from the stomachs of 25 out of 29 patients (86%),
      compared to the control group in which none of the 49 patients were free of H.
      pylori in the stomach 11 months after completion of therapy. There were no
      reported side effects with this triple therapy. None of the H. pylori-eradicated
      patients showed a recurrence of peptic ulcer disease; three of the four patients
      whose H. pylori was not eradicated by triple therapy showed a peptic ulcer
      recurrence within the study period, whereas 16 out of 49 patients in the control
      group had a peptic ulcer recurrence. CONCLUSIONS: This new triple therapy was
      effective in the eradication H. pylori, had very few side effects and greatly
      reduced the rate of recurrent peptic ulcers.

PMID- 8574733
TI  - Peptic ulcer recurrence after Helicobacter pylori eradication: a 5-year follow-up
      study.
AB  - OBJECTIVE: To investigate whether eradication of Helicobacter pylori prevents
      peptic ulcer recurrence in the long term. PATIENTS AND METHODS: We treated 81
      patients with endoscopically proven H. pylori-related peptic ulcers (39 with
      gastric ulcers and 42 with duodenal ulcers) with either amoxycillin or
      clarithromycin in combination with a proton-pump inhibitor or a histamine H2
      receptor antagonist. The patients were followed for a recurrence of peptic ulcers
      for at least 5 years. Recurrence was assessed by endoscopy and the status of H.
      pylori was evaluated by culture, a rapid urease test and a histological
      examination. RESULTS: After 5 years of follow-up, the rate of recurrence of H.
      pylori-related duodenal ulcers decreased significantly (P < 0.0001) in the H.
      pylori-eradicated patients compared with non-eradicated patients. However, in the
      gastric ulcer group, there was no significant reduction in the recurrence rate.
      CONCLUSIONS: Our findings suggest that eradication of H. pylori significantly
      reduces the rate of duodenal ulcer relapse and that this relapse is associated
      with the presence of H. pylori. Therefore, H. pylori eradication may be
      considered a definitive cure for duodenal ulcers.

PMID- 8574734
TI  - Omeprazole-based antimicrobial therapies: results in 198 Helicobacter pylori
      positive patients.
AB  - AIM: To compare the efficacies of omeprazole-based antimicrobial therapies in
      Helicobacter pylori-positive patients. PATIENTS AND METHODS: We report the
      results of seven therapeutic trials combining omeprazole, clarithromycin,
      amoxycillin, colloidal bismuth subcitrate and tinidazole in 198 patients (peptic
      ulcer disease/non-ulcerative dyspepsia, 137/61) to eradicate H. pylori infection.
      The diagnosis of infection was performed by Sydney system biopsies, compliance
      was checked after a pill count at the end of the treatment and eradication was
      assessed at least 4 weeks after the end of the treatment either by the Sydney
      system for peptic ulcer disease or the urease breath test for non-ulcerative
      dyspepsia. RESULTS: When results were analysed on a protocol basis, the only
      significant difference in eradication (P = 0.006) was found between the total
      population of patients treated with amoxycillin-based combinations (27
      eradications out of 48 patients) and those given a treatment that included
      clarithromycin (84 eradications out of 108). Forty-two patients (21%) dropped out
      either because of side effects (10 among patients taking clarithromycin and two
      taking amoxycillin) or because they were lost to follow-up (27 patients). Out of
      64 patients with active ulcers, 43 (67%) were both H. pylori-negative and ulcer
      free 4-8 weeks after the end of therapy, 12 out of 64 (19%) were ulcer-free but
      remained H. pylori-positive and nine out of 64 (14%) were H. pylori-positive and
      had active ulceration.

PMID- 8574735
TI  - Combination therapy with mucosal protective agent for the eradication of
      Helicobacter pylori.
AB  - OBJECTIVE: To investigate the effect of plaunotol in combination with proton-pump
      inhibitors on Helicobacter pylori eradication in patients with gastric ulcer.
      PATIENTS AND METHODS: We studied 65 H. pylori-positive gastric ulcer patients.
      They were randomly assigned to five treatment groups: omeprazole (group I, n =
      8), lansoprazole (group II, n = 13), lansoprazole+plaunotol (group III, n = 12),
      lansoprazole+clarithromycin (group IV, n = 16) and
      lansoprazole+plaunotol+clarithromycin (group V, n = 16). Ulcer status was
      diagnosed by endoscopy and H. pylori status by culture, histology, a urease test
      and a urea breath test at baseline, and after 8 and 12 weeks. The clearance and
      eradication rates were compared in each group. RESULTS: The healing rates in
      groups I-V were 100, 92, 100, 100 and 100%, respectively; clearance rates were 0,
      23, 42, 50 and 75%, respectively; and eradication rates were 0, 0, 8, 38 and 69%,
      respectively. CONCLUSION: Combination therapy with plaunotol is efficacious for
      the eradication of H. pylori in gastric ulcer patients.

PMID- 8574736
TI  - Rationale for the choice of antibiotics for the eradication of Helicobacter
      pylori.
AB  - AIM: To review data on the efficacy of antibiotics currently available for the
      eradication of Helicobacter pylori. RESULTS: The main problem with current
      therapy is the resistance of H. pylori to the compounds used, with the exception
      of amoxycillin and tetracyclines. Primary resistance to metronidazole reaches 80
      90% in tropical countries and may reach 50% in some European countries. Primary
      resistance to macrolides does occur but at a much lower level, although
      apparently linked to the level of consumption of these drugs in a given country.
      Resistance may also be acquired during monotherapy with antibiotics. Most of the
      antimicrobial agents, except bismuth salts, have a systemic effect. Nevertheless,
      their activity is dependent on the pH of the stomach because H. pylori lives in
      the mucus. Compounds that may achieve high mucosal concentrations, such as
      macrolides, are effective when the stomach pH is raised. The growth of H. pylori
      as sessile organisms may impair antibiotic efficacy. CONCLUSIONS: The best
      eradication rate is achieved when two antimicrobial agents are used in
      combination with an antisecretory compound. Amoxycillin+clarithromycin with a
      proton-pump inhibitor is therefore recommended.

PMID- 8574737
TI  - Clarithromycin for treatment of Helicobacter pylori infections.
AB  - BACKGROUND: A better appreciation of the causal relationship between Helicobacter
      pylori infection and peptic ulcer disease and the benefit conferred by curing
      this infection has led to the recommendation that all patients with duodenal
      ulcer disease receive anti-H. pylori treatment. Multi-drug regimens, including
      bismuth, metronidazole and tetracycline or amoxycillin with an antisecretory
      agent, are successful in > 90% of treated patients but the emergence of
      metronidazole-resistant H. pylori has begun to limit their effectiveness. DESIGN:
      The search for the optimal anti-H. pylori treatment has focused on simplifying
      the regimen (to decrease adverse drug-related events and increase patient
      compliance), while retaining the excellent clinical results of the traditional
      multi-drug regimens. This article reviews the data concerning clarithromycin for
      treatment of H. pylori infections. RESULTS: Numerous evaluations have shown that
      clarithromycin has desirable attributes for anti-H. pylori treatment:
      clarithromycin is resistant to gastric acid, penetrates in high concentrations
      into gastric tissue and mucus, shows excellent antimicrobial activity against H.
      pylori, results in a high cure rate when used in two- and three-drug
      combinations, is associated with a low incidence of acquired H. pylori resistance
      and is well tolerated. Successful clarithromycin therapies include
      clarithromycin+omeprazole, clarithromycin+amoxycillin, or
      clarithromycin+omeprazole+tinidazole or metronidazole, and clarithromycin triple
      therapy. CONCLUSION: Clarithromycin may become an integral component of anti-H.
      pylori therapy.

PMID- 8574738
TI  - The influence of Helicobacter pylori infection on the progression of gastric
      mucosal atrophy and occurrence of gastric cancer.
AB  - AIM: To study the effects of Helicobacter pylori infection on the progression of
      gastric mucosal atrophy and the development of gastric cancer. PATIENTS AND
      METHODS: We investigated the extension of the atrophic area as assessed on the
      basis of the Kimura-Takemoto atrophic patterns and the development of gastric
      cancer in a selected sample of 64 patients who were endoscopically followed up
      for more than 3 years, and who showed H. pylori infection by culture at the start
      of the investigation and at some stages during the follow-up. RESULTS: No
      progression of atrophy was observed in 14 patients who were H. pylori-negative at
      the beginning of the follow-up, whereas various degrees of expansion of the
      atrophic area were found in 22% of 50 positive cases. Well differentiated mucosal
      cancer was diagnosed in four patients during the follow-up. These patients
      displayed moderate to severe atrophy. At the beginning of the follow-up, 50% of
      patients were H. pylori culture-positive, but all patients had H. pylori
      antibodies in their blood. CONCLUSIONS: The results support the view that H.
      pylori infection influences the development of atrophic gastritis and is related
      to the pathogenesis of gastric cancer.

PMID- 8574739
TI  - Dual therapy with lansoprazole and clarithromycin for eradication of Helicobacter
      pylori.
AB  - AIM: To evaluate the eradication of Helicobacter pylori by therapy with a
      combination of 60 mg lansoprazole and 800 mg clarithromycin. PATIENTS AND
      METHODS: In an open therapeutic trial, 30 H. pylori-positive patients with active
      ulcer disease took 30 mg lansoprazole twice a day and 400 mg clarithromycin twice
      a day for the first 2 weeks, followed by 30 mg lansoprazole once a day for 4-6
      weeks. Endoscopy was performed both before and at the end of therapy, and 4 weeks
      after the end of the therapy. H. pylori was detected by using a combination of
      smear, culture and tissue sections. RESULTS: Complete pain relief occurred within
      3 days in all patients and all ulcers were healed by the end of the therapy. The
      H. pylori clearance rate was 83.3% and the eradication rate was 73.3%. A minor
      side effect (metallic taste) was reported by only one patient (3.3%).
      CONCLUSIONS: Therapy with a combination of 60 mg lansoprazole and 800 mg
      clarithromycin is efficacious in the eradication of H. pylori and has the
      advantage of a low incidence of side effects and quick pain relief for patients
      with active ulcers.

PMID- 8574740
TI  - Effect of Helicobacter pylori eradication on the healing and recurrence of peptic
      ulcer: combination therapy with low-dose omeprazole and clarithromycin.
AB  - AIM: To investigate the effect of eradication of Helicobacter pylori using
      combination therapy with low-dose omeprazole and clarithromycin on the healing
      and recurrence of peptide ulcers. PATIENTS AND METHODS: We studied 60 patients
      with active duodenal ulcers and 60 with gastric ulcers who were H. pylori
      positive by the rapid urease test and a histological examination of antral biopsy
      specimens. The eradication method used was a combination of omeprazole (20 mg a
      day) and clarithromycin (400 mg twice a day). The patients were followed up for
      24 months after the end of the treatment. H. pylori infection and the ulcer stage
      were investigated by endoscopy every 6 months. We assessed the relationship
      between H. pylori infection, ulcer healing to a white scar and ulcer recurrence
      after combination therapy. RESULTS: H. pylori was eradicated in 23 out of 120
      patients (22%), with suppression in 101 out of 120 patients (84%). The rate of
      ulcer healing to a white scar 6 months after treatment was significantly higher
      and the ulcer recurrence rate within 2 years after treatment was significantly
      lower in patients with H. pylori suppression or eradication than in those
      continuously positive for the organism. CONCLUSIONS: These results suggest that
      not only the eradication but also the suppression of H. pylori may improve ulcer
      healing and reduce the rate of relapse.

PMID- 8574741
TI  - Relationship between Helicobacter pylori infection, atrophic gastritis and
      gastric carcinoma in a Japanese population.
AB  - AIM: To evaluate the possible relationship between Helicobacter pylori infection
      and gastric carcinoma, and its precursor lesion, intestinal metaplasia, in a
      Japanese population. SUBJECTS AND METHODS: H. pylori infection was identified by
      the presence of anti-H. pylori immunoglobulin (Ig)G. The frequency of H. pylori
      infection was compared in 109 patients with gastric carcinoma, the same number of
      patients with atrophic gastritis and asymptomatic controls matched for age, sex
      and place of birth. To study the relation between H. pylori and intestinal
      metaplasia, sera and gastric antral and corpus mucosal biopsies were obtained
      from 58 asymptomatic controls, 92 patients with chronic gastritis and 80 patients
      with peptic ulcer. RESULTS: The presence of IgG antibody to H. pylori was
      significantly more frequent in those with gastric carcinoma than in asymptomatic
      controls (87.2 versus 74.3%; odds ratio 2.4; 95% confidence interval 1.2-4.8).
      The positive rates of H. pylori IgG antibody were 80.7% in patients with atrophic
      gastritis. Mean serum gastrin and pepsinogen II levels in H. pylori-positive
      patients were higher than those in H. pylori-negative patients. Serum gastrin and
      pepsinogen I levels were significantly higher in controls than gastric carcinoma
      patients (P < 0.01 and P < 0.05, respectively). Serum pepsinogen I:II ratios were
      significantly lower in controls than in gastric carcinoma patients (P < 0.01).
      Intestinal metaplasia was strongly associated with H. pylori infection, and was
      only found in patients with IgG antibodies to H. pylori. CONCLUSIONS: These
      results suggest that H. pylori infection is associated with the development of
      gastric cancer by providing a suitable environment for carcinogenesis of the
      gastric mucosa, such as gastric atrophy and intestinal metaplasia.

PMID- 8574742
TI  - Immunogenetic analysis of the human leukocyte antigen DQA1 locus in patients with
      duodenal ulcer or chronic atrophic gastritis harbouring Helicobacter pylori.
AB  - AIM: To examine the human leukocyte antigen (HLA)-DQA1 locus in patients
      harbouring Helicobacter pylori with chronic atrophic gastritis or duodenal ulcer
      as part of an investigation into immunogenetic differences in the host. SUBJECTS
      AND METHODS: We examined 116 patients harbouring H. pylori (55 patients with
      chronic atrophic gastritis, 61 with duodenal ulcers) and 28 H. pylori-negative
      healthy controls for HLA-DQA1 genotypes. H. pylori infection was determined by
      culturing biopsy samples from the gastric body and antrum and by enzyme-linked
      immunosorbent assay. HLA-DQA1 typing was carried out by the polymerase chain
      reaction-restriction fragment length polymorphism method. RESULTS: The allele
      frequency of DQA1*0102 was significantly higher in H. pylori-negative controls
      (0.250) than in H. pylori-positive duodenal ulcer patients (0.090). In contrast,
      the allele frequency of DQA1*0301 was significantly lower in H. pylori-negative
      controls (0.214) than in H. pylori-positive duodenal ulcer patients (0.418).
      CONCLUSION: These results suggest that there are genetic differences in the HLA
      DQA1 locus between H. pylori-positive duodenal ulcer patients and H. pylori
      negative healthy controls.

PMID- 8574743
TI  - Detection and identification of cagA of Helicobacter pylori by polymerase chain
      reaction.
AB  - AIM: To investigate cagA, which is linked to vacuolating cytotoxin activity of
      Helicobacter pylori, using molecular techniques. MATERIALS AND METHODS: A
      polymerase chain reaction method was used to detect cagA from clinical isolates
      of H. pylori. H. pylori strain diversity was examined by DNA restriction fragment
      length polymorphism (RFLP) patterns with cagA as a probe. RESULTS: The detection
      rate of the cagA products was significantly higher in strains from gastric ulcer
      patients than in those of chronic gastritis patients (78.9 versus 56.0%; P <
      0.05), and RFLP patterns were different between gastric ulcer and gastric cancer
      strains. CONCLUSIONS: A polymerase chain reaction method established for the
      detection of cagA proved to be rapid and useful. Analysis of cagA may therefore
      be a useful genetic technique for the study of strain diversity.

PMID- 8574744
TI  - Effect of ammonia on cell-cycle progression of human gastric cancer cells.
AB  - AIM: Ammonia is a cytotoxic factor of Helicobacter pylori that is involved in
      gastric mucosal injury. This study was designed to show whether ammonia has an
      effect on the cell-cycle progression in human gastric cells in vitro. MATERIALS
      AND METHODS: We studied the effects of ammonia and ammonium chloride on cell
      growth and cell-cycle progression of the human gastric cancer cell line HGC-27.
      We cultured HGC-27 cells and counted viable cells by trypan blue dye exclusion 24
      h after the addition of various concentrations of ammonia or ammonium chloride.
      DNA contents of nuclei were analysed by flow-cytometry. RESULTS: Ammonia and
      ammonium chloride inhibited the proliferation of HGC-27 cells dose-dependently.
      Flow-cytometric analysis showed S-phase accumulation of HGC-27 cells treated with
      ammonia and ammonium chloride at cytostatic doses. CONCLUSIONS: These results
      suggest that ammonia and ammonium chloride inhibit the growth of gastric cells in
      S phase. This mechanism may make a significant contribution to the pathogenesis
      of Helicobacter pylori-associated gastric mucosal atrophy.

PMID- 8574745
TI  - Differences in urease activity in live Helicobacter pylori cultured from patients
      with gastroduodenal diseases.
AB  - AIM: To develop a reliable method for measuring urease activity in live bacteria,
      and to determine whether there are any differences in urease activity among the
      Helicobacter pylori strains involved in gastroduodenal disease. DESIGN: The
      stability of the method was examined in the first phase of the study, and in a
      second phase the mean urease activity in clinical isolates from different groups
      of patients was compared. MATERIALS AND METHODS: To assess the stability and
      reliability of the method, we assessed the relationship between bacterial
      proliferation and urease activity, the relationship between the number of
      bacteria and the optical density, and differences in urease activity among
      bacterial generations. Ten of the 3-day-old colonies in the third generation were
      suspended in phosphate-buffered saline, and urease activity was measured as 10(5)
      colony-forming units/ml bacteria. RESULTS: The assay system appeared to be
      effective, because the urease activity of live bacteria in the logarithmic growth
      period was constant, the number of bacteria and the optical density showed a
      linear correlation on a bilogarithmic graph and there was no significant
      difference in urease activity over three generations. With this method, urease
      activity varied from 0.192 to 80.42 mIU/10(5) colony-forming units of
      bacteria/ml. There was no significant difference in the mean urease activity of
      live bacteria from controls, gastric ulcer patients and duodenal ulcer patients.
      However, the mean urease activity in bacteria from cancer patients was
      significantly higher than that of controls or duodenal ulcer patients.
      CONCLUSIONS: H. pylori strains derived from cancer patients, which have
      relatively high levels of urease activity, might easily colonize the stomach and
      lead to much mucosal damage during the long course of H. pylori infection.

PMID- 8574746
TI  - Adherence of Helicobacter pylori to cultured human gastric carcinoma cells.
AB  - AIM: To examine the binding activity of Helicobacter pylori to cultured gastric
      epithelial cells using flow cytometry. MATERIALS AND METHODS: We evaluated the
      adherence of 15 H. pylori strains to cultured gastric cancer (MKN45) cells by
      flow cytometric analysis. Other bacterial strains were also analysed for their
      adherence to MKN45 cells. In addition, we examined the effect of fetuin on the
      adherence of H. pylori to MKN45 cells. RESULTS: H. pylori strains adhered to
      MKN45 cells at rates of between 49 and 93.7%, with a mean of 75.3%. In contrast,
      the rates of Escherichia coli, Shigella flexneri, Vibrio cholerae and Yersinia
      enterocolitica adherence to MKN45 cells were 69.1, 5.9, 11.7 and 33.1%,
      respectively. Fetuin had no inhibitory effect on the adherence of H. pylori to
      MKN45 cells in the flow cytometric analysis. CONCLUSIONS: A flow cytometric
      analysis using MKN45 cells proved to be an objective and sensitive method for
      evaluating the adherence of H. pylori, showing close adherence between this
      organism and gastric epithelial cells.

PMID- 8574747
TI  - Influence of Helicobacter pylori infection and the effects of its eradication on
      gastric emptying in non-ulcerative dyspepsia.
AB  - AIM: The aim of the present study was to clarify the effects of Helicobacter
      pylori infection and its eradication on gastric emptying. SUBJECTS AND METHODS:
      Out of a total of 52 patients with non-ulcerative dyspepsia, 34 H.pylori-positive
      patients were enrolled. Antimicrobial drugs for the eradication of H. pylori were
      administered to 19 out of the 34 H. pylori-positive patients. Gastric emptying
      was evaluated according to the acetaminophen method. Inflammatory changes and
      intracellular periodic acid-Schiff-positive substances in the antral mucosa were
      examined in biopsy specimens. RESULTS: Although gastric emptying was
      significantly prolonged in the patients with non-ulcerative dyspepsia compared
      with the control group (P < 0.01), there was no difference in gastric emptying
      between H. pylori-positive and -negative patients, with all patients showing
      significantly less gastric emptying than the control group. The H. pylori
      eradication rate was 58% (11 out of 19) and gastric emptying improved
      significantly in seven patients whose infection was eradicated and whose
      dyspeptic symptoms disappeared. The ammonia concentration in gastric juice,
      inflammatory changes in the gastric mucosa and the index of periodic acid-Schiff
      positive substances improved significantly when H. pylori was successfully
      eradicated compared with patients in whom eradication was unsuccessful. As gut
      hormones may affect gastroduodenal motility associated with H. pylori infection,
      we also studied the levels of serum gastrin and cholecystokinin. In the patients
      whose infection was eradicated, serum gastrin decreased significantly, but the
      cholecystokinin level did not change significantly, although there was a non
      significant trend for cholecystokinin to increase. CONCLUSIONS: These results
      suggest that delayed gastric emptying is partly associated with H. pylori
      infection and that the infection may contribute to the development of non
      ulcerative dyspepsia.

PMID- 8574748
TI  - The role of CXC chemokines as regulators of angiogenesis.
AB  - The regulation of angiogenesis is fundamental to a variety of physiological and
      pathological processes. Although a number of factors have been identified that
      induce neovascularization, it is becoming increasingly apparent that endogenous
      angiostatic factors may play an important role in the regulation of angiogenesis
      during wound repair, chronic inflammation, and growth of solid tumors. In this
      review, we demonstrate that the CXC chemokine family of cytokines display
      disparate angiogenic activity depending upon the presence or absence of the ELR
      motif, a structural amino acid motif previously found to be important in receptor
      ligand binding on neutrophils. CXC chemokines containing the ELR motif are potent
      angiogenic factors, inducing both in vitro endothelial chemotaxis and in vivo
      corneal neovascularization. In contrast, the CXC chemokines that lack the ELR
      motif, PF4, IP-10, and MIG, not only fail to induce significant in vitro
      endothelial cell chemotaxis or in vivo corneal neovascularization, but are found
      to be potent angiostatic factors in the presence of CXC chemokines containing the
      ELR motif. These findings suggest that the CXC chemokine family can display
      disparate angiogenic activity that depends upon the presence or absence of the
      ELR motif. Furthermore, these studies support the notion that the net biological
      balance in the magnitude of expression of angiogenic and angiostatic CXC
      chemokines at either the site of wound repair or during tumorigenesis may be
      important in the regulation of net angiogenesis.

PMID- 8574749
TI  - In vivo modulation of human neutrophil function by pentoxifylline in patients
      with septic syndrome.
AB  - The influence of pentoxifylline on human polymorphonuclear granulocyte (PMN)
      respiratory burst activity (RBA) was studied in 23 patients fulfilling the
      established criteria of sepsis and in 10 healthy donors. Pentoxifylline (PTX) was
      administered (5 mg/kg) by intravenous infusion in 13 septic patients over a
      period of 180 min. The control group consisted of 10 patients with septic
      syndrome who received an infusion of physiological saline. For determination of
      RBA, 10 mL of blood was drawn at respective time intervals before, during, and
      after treatment with PTX or a placebo. RBA measurements were performed using a
      chemiluminescence assay after stimulation of PMN with formyl-methionyl-leucyl
      phenylalanine (FMLP), phorbol-myristate-acetate, and opsonized zymosan,
      respectively. RBA measurements of each patient were performed in replicate
      samples. CL was measured for 1 h at respective time intervals (1, 3, 5, 8, 10, 15
      min etc). RBA of PMN of septic patients was compared with RBA of PMN of healthy
      donors and patients receiving PTX were compared with controls. Our results
      demonstrate that PMN of patients with sepsis had an increased oxidative response
      compared with healthy donors. We found that PTX administered intravenously was
      able to reduce this reactivity. RBA was significantly decreased during PTX
      infusion when PMN were stimulated with FMLP and phorbol-myristate-acetate,
      compared with the control group. No significant decrease was observed when PMN
      were stimulated with opsonized zymosan. These data suggest that PTX may be a
      valuable drug in septic state.

PMID- 8574750
TI  - Amelioration of endotoxin-induced acute lung injury in pigs by HWA 138 and A 80
      2715: new analogs of pentoxifylline.
AB  - We have evaluated the potential therapeutic effects of the xanthine derivatives
      HWA 138 (1-(5 hydroxy-5-methylhexyl)-3-methylxanthine) and A 80,2715 (1-(5
      hydroxy-5-methylhexyl)-3-methyl-7-propylxanthine) on acute lung injury in
      endotoxemic pigs when administered following the septic insult. Salmonella
      abortus equi endotoxin (LPS) was given as a continuous intravenous infusion of 2
      micrograms/kg/h over a period of 8 h. 1 h after the start of the LPS infusion the
      animals received a bolus injection followed by continuous infusion of A 80,2715
      (3 mg/kg + 1.5 mg/kg/h; n = 6), HWA 138 (3 mg/kg + 1.5 mg/kg/h; n = 6), or saline
      (LPS control; n = 6). Treatment with A 80,2715 or HWA 138 inhibited the LPS
      induced increases in the pulmonary artery pressure (p < .05; ANOVA) and in lung
      wet/dry weight ratio (p < .05), and ameliorated the LPS-induced deterioration in
      lung mechanics (decreased lung dynamic compliance (p < .05); increased peak
      airway pressure (p < .05)). Xanthine treatment, however, failed to significantly
      improve arterial PO2 and did not affect peripheral leukopenia. The results of
      this study suggest a potential therapeutic role for HWA 138 and A 80,2715 in
      attenuating endotoxin-induced acute lung injury.

PMID- 8574751
TI  - Elevated IL-8 production by trauma patients' monocytes is associated with
      elevated secretion of TNF alpha.
AB  - IL-8 is a recently described chemokine that increases polymorphonuclear
      neutrophil infiltration and has been implicated in inflammatory pathology. This
      study assesses monocyte (M phi) interleukin-8 (IL-8) levels in severe trauma
      patients (injury severity score > 16) who have elevated levels of M phi cell
      associated tumor necrosis factor alpha (TNF alpha), a major marker for systemic
      inflammatory response syndrome after injury. We demonstrate elevated (p = .0007)
      levels of M phi IL-8 only in those trauma patients who also have increased (p =
      .0001) M phi-secreted TNF alpha whereas the patients having normal M phi-secreted
      TNF alpha levels have normal or even decreased M phi IL-8 production. There is no
      association between M phi IL-8 production and cell-associated TNF alpha levels. M
      phi induction by Fc gamma RI cross-linking, a common induction pathway in trauma
      patients' M phi that increases the production of both cell-associated and
      secreted TNF alpha, can also increase (p = .0022) M phi IL-8 levels. Therefore,
      post-trauma elevation of M phi IL-8 levels may be associated with increased
      secreted TNF alpha resulting from, at least in part, Fc gamma RI cross-linking
      stimulation in vivo.

PMID- 8574752
TI  - Platelet participation in liver injury from gram-negative bacterial
      lipopolysaccharide in the rat.
AB  - Intravenous administration of lipopolysaccharide (LPS) to rats results in
      multifocal, primarily midzonal hepatic necrosis. The hepatic injury is associated
      with inflammation and is dependent on neutrophils and the coagulation system.
      After LPS injection into rats, plasma fibrinogen concentration and numbers of
      blood platelets and leukocytes decrease. Results of our studies, using
      immunocytochemistry for the detection of neutrophils and 111indium-labeling to
      identify platelets, indicate that both neutrophils and platelets accumulate
      within the liver early after administration of LPS to rats. The accumulation of
      platelets in the liver before the onset of injury suggested that platelets
      contribute to the manifestation of LPS-induced hepatotoxicity. To test this
      hypothesis, the number of circulating blood platelets was decreased by the
      administration of an anti-rat platelet serum (APS) before LPS administration. The
      consequent thrombocytopenia by APS administration was associated with an
      attenuation of both LPS-induced liver injury and the activation of the
      coagulation system. However, the APS treatment did not prevent the hepatic
      neutrophil accumulation. These results suggest that platelets contribute to the
      pathogenesis of liver injury after LPS administration, perhaps through their
      integral role in coagulation and/or interaction with neutrophils, but they do not
      appear to contribute to hepatic neutrophil accumulation.

PMID- 8574753
TI  - A natural glycoprotein inhibitor (NIF) of CD11b/CD18 reduces leukocyte adhesion
      in the liver after hemorrhagic shock.
AB  - This study was designed to assess the effect of neutrophil inhibitory factor
      (NIF), a novel specific inhibitor of CD11b/CD18 on hepatic leukocyte trafficking
      by intravital microscopy 5 h after hemorrhagic shock. Anesthetized rats were
      instrumented for invasive hemodynamical monitoring. Hemorrhagic shock was induced
      for 60 min by withdrawal of arterial blood (mean arterial blood pressure = 40
      mmHg). Rats were adequately resuscitated for 5 h to achieve a mean arterial blood
      pressure > 100 mmHg and were randomly assigned to blinded treatment with NIF or
      placebo control protein administered as a single intravenous bolus (10 mg/kg) at
      the time of resuscitation. Intrahepatic leukocyte adhesion was evaluated by in
      vivo fluorescence microscopy. There were no significant differences observed in
      hemodynamic parameters between the shock groups throughout the study, however,
      NIF significantly reduced firm leukocyte adhesion in liver sinusoids. The results
      suggest that NIF may be beneficial in the attenuation of the pathological shock
      induced leukocyte adhesion.

PMID- 8574754
TI  - The gut: a cytokine-generating organ in systemic inflammation?
AB  - The aim of this study was to test the hypothesis that the gut is capable of
      becoming a cytokine-generating organ following either a lethal or nonlethal
      inflammatory insult. Adult male rats were given an intraperitoneal challenge with
      saline, or with a nonlethal (.1 mg/g) or LD50 (.5 mg/g) dose of zymosan.
      Mesenteric lymph nodes, efferent mesenteric lymph, liver, spleen, and blood
      (portal and systemic) were obtained at 2, 4, 6, 8, or 10 h post challenge.
      Organs, lymph, and blood were tested for bacterial translocation (BT); blood and
      lymph were assayed for tumor necrosis factor (TNF) and IL-6. After .1 mg/g
      zymosan, BT was limited to the mesenteric lymph node complex only; .5 mg/g
      zymosan promoted BT to blood, mesenteric lymph, and organs (p < .05 vs. control
      or .1 mg/g zymosan). The magnitude of portal bacteremia was greater than systemic
      bacteremia (p < .003). Serum TNF peaked at 2 h (p < .05 vs. control), and serum
      IL-6 peaked at 4-6 h (p < .05 vs. control) post zymosan challenge. Portal and
      systemic bioactivity was similar for either cytokine, and serum bioactivity did
      not correlate with zymosan dose. TNF bioactivity was increased in the mesenteric
      lymph at 2 h post challenge with .5 mg/g zymosan only (p < .05 vs. control or .1
      mg/g zymosan). IL-6 bioactivity was increased in the mesenteric lymph at 4
      through 10 h post zymosan challenge (p < .05 vs. control), but was similar with
      either dosage of zymosan. In conclusion, the gut may be capable of producing
      cytokines in response to an inflammatory stimulus, even in the absence of portal
      or systemic spread of bacteria. The magnitude of the cytokine response does not
      correlate with the magnitude of bacterial translocation.

PMID- 8574755
TI  - Alterations in alveolar macrophage tumor necrosis factor (TNF) response following
      hemorrhagic shock.
AB  - The purpose of this study was to determine if hemorrhagic shock alters the
      alveolar macrophage (M phi) tumor necrosis factor (TNF) response to
      lipopolysaccharide (LPS) stimulation. New Zealand White rabbits underwent
      hemorrhage and resuscitation. At 1, 2, 3, 5, and 7 days post-shock, both M phis
      and peripheral whole blood monocytes were incubated in vitro with saline or
      Escherichia coli LPS. The supernatants were assayed for TNF activity using the
      L929 bioassay. Alveolar M phis from hemorrhaged animals showed reduced TNF
      activity during the first 5 days post-hemorrhage. Maximal depression of TNF
      activity was observed on days 3 and 5 post-hemorrhage (p < .05). In comparison,
      peripheral whole blood monocytes showed an increased TNF response on post-shock
      days 2 and 3. These results suggest that hemorrhagic shock and resuscitation
      differentially affect TNF response in alveolar and peripheral blood M phi
      populations.

PMID- 8574756
TI  - Exposure of the lateral enterocyte membrane by dissociation of calcium-dependent
      junctional complex augments endocytosis of enteric bacteria.
AB  - Intestinal bacterial translocation is facilitated in a variety of clinical
      conditions involving increased intestinal permeability, such as shock and trauma.
      Because there is both in vivo and in vitro evidence that enteric bacteria can be
      internalized by intestinal epithelial cells, experiments were designed to test
      the effect of increased intestinal permeability on enterocyte endocytosis of
      enteric bacteria. Mature, confluent cultures of HT-29 enterocytes were placed in
      a calcium-free solution for 1 h. Enterocyte viability was not noticeably altered,
      but transepithelial electrical resistance was significantly decreased (indicating
      a decrease in epithelial junctional integrity), and the enterocytes were pulled
      apart. Electron microscopic observations revealed enteric bacteria preferentially
      adherent on the exposed enterocyte lateral surface, and the numbers of viable
      enteric bacteria (Listeria monocytogenes, Salmonella typhimurium, Proteus
      mirabilis, Escherichia coli, and Enterococcus faecalis) internalized by these
      enterocytes were significantly increased. Restoration of calcium restored
      confluency to enterocyte cultures, and bacterial internalization reverted to
      control levels. Thus, calcium-dependent junctional integrity might play a role in
      augmenting bacterial translocation in clinical conditions associated with
      increased intestinal permeability.

PMID- 8574757
TI  - Effect of phenytoin on smoke inhalation injury in sheep.
AB  - To determine whether the anti-inflammatory effects of phenytoin might reduce
      cardiopulmonary dysfunction we studied the effects of phenytoin treatment on
      acute lung injury induced by smoke inhalation. Twenty-one chronically
      instrumented sheep were observed for 24 h after smoke inhalation injury.
      Myocardial contractility was evaluated by left ventricular end-systolic pressure
      diameter relationship (LVESPDR) with a pair of ultrasonic transducers and strain
      gauge transducer. In the control group (n = 6), uninjured sheep were given a
      bolus of phenytoin (12.5 mg/kg). Smoke-insufflated sheep were divided into
      nontreatment (n = 7) and phenytoin (n = 8) groups. Phenytoin alone had no effects
      in uninjured sheep except an early rise in heart rate and LVESPDR. In the group
      given smoke without treatment, there was a significant increase in pulmonary
      artery pressure and pulmonary vascular resistance index and a decrease in cardiac
      index. Pulmonary vascular changes were attenuated by treatment with phenytoin.
      Pulmonary transvascular fluid flux was evaluated by using a lung lymph fistula.
      LVESPDR fell in the smoke group but not in the group given phenytoin. There was a
      marked increase in lung lymph flow with smoke inhalation but this phenomenon was
      not affected by phenytoin treatment. In conclusion, phenytoin treatment reduced
      early hemodynamic depression.

PMID- 8574758
TI  - Effect of recombinant human granulocyte colony-stimulating factor on hemodynamic
      and cytokine response in a porcine model of Pseudomonas sepsis.
AB  - To investigate the effect of recombinant human granulocyte colony-stimulating
      factor (rhG-CSF) on sepsis, chronically catheterized conscious pigs were
      challenged with Pseudomonas aeruginosa (8 x 10(7) colony-forming units kg-1 h-1)
      for 84 h (Group A, n = 8). Group B (n = 7) also received rhG-CSF at 5 micrograms
      kg-1 d-1, the first dose being given 30 min before starting bacterial infusion.
      Two of the animals in Group A died from pulmonary failure, whereas all those
      treated with rh-GCSF survived. Fever, severe pulmonary hypertension and systemic
      hypotension--the latter accompanied at first by a transient hypodynamic, and
      later a hyperdynamic response--were observed in all of the animals. In Group B,
      however, the rise in temperature, mean pulmonary arterial pressure (at a later
      stage of the observation), plasma levels of tumor necrosis factor, and endotoxin
      were significantly less than in Group A. In the rhG-CSF-treated pigs, an initial
      leukopenia completely recovered within 24 h (p < .05 vs. Group A). These data
      suggest that rhG-CSF might be beneficial in the treatment of sepsis.

PMID- 8574759
TI  - Polymorphonuclear leukocytes: their role as central cellular elements in shock
      pathogenesis.

PMID- 8574760
TI  - Interpretation of diagnostic implications of fluorescence parameters for
      atherosclerosis in fibrous, calcified and normal arteries.
AB  - Fluorescence spectroscopy presents great interest for the diagnosis of
      atherosclerosis. Nevertheless there are some difficulties in the interpretation
      of diagnostic information. This could be overcome by precise methods of
      extraction of the diagnostic parameters and convenient statistical analysis,
      which are the subject of this work. Fluorescence excitation-emission matrices
      from different categories of coronary arteries were developed and used to derive
      the optimum excitation wavelength on the one hand and to assign the spectra to
      specific chromophores on the other hand. Simple dimensionless functions (Fi) were
      formed by the ratio of the intensities at selected wavelength and the logistic
      model was used for statistical analysis. Decision surfaces were drawn and it was
      estimated that the probability of correct classification is 88%. The algorithm
      correctly diagnoses 97% of healthy from diseased samples and 80% of fibrous from
      calcified coronary arteries.

PMID- 8574761
TI  - The role of thermal feedback in electrosurgical tissue heating.
AB  - Thermal dependence of tissue resistivity was incorporated into a compartmental
      tissue model that predicted the interaction between power delivery from
      electrosurgical units (ESUs) and tissue heating. Simulations showed that as
      tissue resistance declines with heating, a positive feedback loop from tissue to
      generator is created that can promote alternate site burning. This study
      describes how the thermal behaviour of tissue resistance influences the output of
      microprocessor-controlled thermal generators, especially when used in the
      monopolar mode.

PMID- 8574762
TI  - Measurement of tear electrolyte concentration and turnover rate using a flexible
      conductimetric sensor.
AB  - Tear fluid conductivity was measured by a non-invasive method. A flexible 3 mm
      wide conductimetric sensor was placed inside the human subjects temporal lower
      cul-de-sac (similar to Schirmer test strip), and used to evaluate electrolyte
      concentration and turnover rate in tear for normal, healthy subjects aged between
      30 to 85 years in a normal, light indoor environment. The tear electrolyte
      concentration was calculated from tear conductivity to give a mean value of 297
      mEq/l (S.D. 30 mEq/l; n = 29) which was consistently with previously reported
      values. Tear turnover rate was calculated by a single exponential equation of
      tear conductivity change, following the application to the eye-drops of 40.0
      milligrams sodium chloride solution. The mean turnover rate was 44.2% per minute
      (S.D. = 13.3% per minute; n = 30), being in agreement with previously reported
      values.

PMID- 8574763
TI  - A generic environment for linear and nonlinear ECG processing.
AB  - Every aspect of cardiac function such as contractibility, depolarization and
      repolarization of cardiac cells, firing rate of pacemaker cells, is under a
      complex neurohumoral regulation. Especially the autonomic neuron system through
      the interplay of its two opposing components, sympathetic and parasympathetic
      (vagal), is controlling cardiac function on a beat to beat basis. Moreover, the
      interaction of sympathetic and parasympathetic systems is a non-linear function,
      with sympathetic tone modulating the response of vagal activation. It has been
      shown that the power of frequency components and especially the ratio of low to
      high frequency power spectra of heart rate variability are reliable indicators of
      sympathovagal balance (A. Malliani et al. 1991. Cardiovascular Neural regulation
      explored in the frequency domain. Circulation, 84 (2) 482-484. The most known
      algorithms of linear and non-linear signal processing have been applied to the
      ECG data recorded from healthy and high risk individuals. These methods together
      with the study and analysis of QRS frequency spectrum will lead to very useful
      conclusions with diagnostic and prognostic information. In this paper we will
      briefly describe the mathematical aspect of these algorithms presenting their
      results for normal and pathological ECG signals.

PMID- 8574765
TI  - Medicine in virtual environments.
AB  - Virtual Environments allow a human to interact with a (computer) system in such a
      way that a high level of presence in a computer-synthesised world is experienced.
      In principle, all human senses are involved with the interaction. Many
      applications may benefit from this type of human-machine interfacing, however,
      few have emerged so far for medicine. In this paper we elaborate on some
      realistic potential applications of Virtual Environment technology in the field
      of medicine. These applications can be found in education/training, therapy,
      surgery, rehabilitation, diagnosis, telemedicine and biomechanics. The value to
      be added to these applications by VE technology lies in the fact that patient
      data or patient models may be moderated to the physician in a more intuitive and
      natural manner. Despite these potentials, the short-term feasibility of these
      applications can be put into question for various reasons. Firstly, the current
      generation of display devices have a resolution that may show to be too low to
      achieve a sufficiently high degree of realism for medical applications. Secondly,
      there are no commercially-available actuators for tactile and force feedback
      which the physician desperately need for the simulation of the contact with the
      (virtual) patient. Thirdly, the enormous computing power required for these
      applications (still) needs a considerable investment. With these limitations in
      mind, we believe that we are at the cradle of a whole new generation of VE
      applications in medicine.

PMID- 8574764
TI  - Multicenter German reference data base for peripheral quantitative computer
      tomography.
AB  - The wide spread use of bone densitometers in Germany and other European countries
      has required the establishment of a validated reference population data base. A
      semianthropomorphic forearm cross-calibration phantom (EFP), developed during a
      concerted research action of the European Union's programme in Biomedical
      Engineering (COMAC-BME), was used to cross-calibrate the peripheral quantitative
      computer tomography (pQCT) devices at four German centers participating in the
      multicenter study. In total, 723 women and 208 men were included in the normal
      data base. No significant regional differences were found between the data of the
      different centers. In addition to the manufacturers calibration standard, proper
      calibration of the pQCT devices could be monitored during collection of the
      normal female and male data base. As a merit of the COMAC-BME study the
      measurements obtained with all pQCT devices thus ensured an uniform reference
      data base for distal radius measurements in Germany.

PMID- 8574766
TI  - Interpretation of multimodal medical images using connectionist and variational
      methods.
AB  - Our medical objective is to match multimodal 3D medical images into a coherent
      model of the patient, from which diagnosis can be assessed and therapeutics
      guided. 3D image segmentation is absolutely necessary to reach this objective. We
      investigate two complementary approaches for segmenting 3D medical images. First
      we present some definitions, basic properties and recent theoretical results
      about formal neural networks, and show that these results can be applied to brain
      tumour segmentation. A variational approach (called the 'snake spline' method) is
      then detailed. We finally show how segmented 3D images can be used for multimodal
      image matching.

PMID- 8574767
TI  - Is ovarian adrenergic innervation essential to gonadal function in adult rats?
AB  - We studied the relative importance of ovarian innervation during different phases
      of female rat sexual development, 30, 40, 45 and 60-day-old. Chemical
      sympathectomy was promoted by long term postnatal treatment with guanethidine
      (GD), an adrenergic neuron blocking agent. The sympathectomized rats exhibited
      delayed puberty and alterations in estrous cycle. Reduced circulating E2, LH and
      Prl levels at 30 days of age were observed, besides decreased steroidal secretory
      responsiveness to gonadotropins in vitro. On the other hand, normal pituitary
      secretory responsiveness to LHRH in vivo and plasma gonadotropin concentrations
      were observed in 60-day-old rats. These data reinforce the view that ovarian
      sympathetic innervation contributes to the regulation of the prepubertal
      development of the ovarian functions.

PMID- 8574768
TI  - Input-output dependence reveals the components of GABAergic modulation in rat
      hippocampal CA3 in vivo.
AB  - Field population spikes, orthodromically elicited (PS2), upon commissural
      stimulation, in the hippocampal CA3 region of the anaesthetized rat, were
      determined at stimulation intensities (Istim) varying from 0.25 to 6 mA. A sharp,
      stimulation-dependent increase in the PS2 amplitude was observed with increasing
      Istim up to 0.5 mA, followed by an exponential decrease in PS2 at higher Istim,
      reaching a steady value with Istim above 3 mA. Intravenous (iv) infusion of
      bicuculline (BIC) increased the PS2, when elicited by Istim between 0.25 and 6
      mA, though the stimulus-response (S-R) curve consistently presented a local
      minimum in between 0.5 to 1 mA. Baclofen (10 and 30 mg/kg iv) dose-dependently
      reduced PS2 at the lowest Istim (0.25 mA), both in control and in BIC-treated
      animals. At higher stimulation intensities, however, baclofen (30 mg/kg iv)
      increased PS2, while barely affecting the population spike in BIC-treated
      animals. The input-output dependence of this CA3 response appeared able to
      provide a convenient in vivo model revealing the components of GABAergic
      modulation.

PMID- 8574769
TI  - The short-term effect of dietary fats on the brain fatty acid composition in
      rats.
AB  - The effects of dietary fats on brain fatty acid composition were studied in
      weanling rats. Three groups of rats were fed for six days a basal diet
      supplemented with a 10% (w/w) of fat as coconut, olive or sunflower oil. There
      were no differences in the saturated and monounsaturated fatty acid content among
      the different groups. The more abundant polyunsaturated fatty acids were
      arachidonic (20:4 n-6) and docosahexaenoic (22:6 n-3) acids. No effect of the
      diet on their amount in brain membranes has been found. We can conclude that the
      brain does not modify its fatty acid composition after a short-time
      administration of these lipids.

PMID- 8574770
TI  - Divalent cation-activated ecto-ATPase activity of rat glomerular mesangial cells.
AB  - Evidence is presented of a Mg2+ and Ca(2+)-activated ATPase at the surface of
      cultured rat glomerular mesangial cells. Substrate specificity was very low when
      different nucleoside-5'-triphosphates were examined. The apparent Km values were
      0.46 and 0.32 mM for Mg(2+)-ATPase and Ca(2+)-ATPase, respectively. Inhibition
      studies have revealed that this enzyme is different from the (Na+ + K+)-ATPase
      and from the divalent cation activated mitochondrial ATPases. Culture in the
      serum-free medium markedly decreased ecto-ATPase activity. Con A treatment
      reduced at 50 micrograms/ml by 15% the Ca(2+)-ATPase activity. Endocytosis of
      serum-treated zymosan (STZ) did not significantly affect ecto-ATPase activity. In
      contrast, endocytosis of STZ by macrophages was accompanied by a biphasic
      response, an increase in Mg(2+)-ATPase and Ca(2+)-ATPase activities after
      ingestion of smaller amounts of STZ and a marked decrease after loading doses of
      STZ.

PMID- 8574771
TI  - Effect of pH upon Ca(2+)-ATPase activity of rat pancreatic islets: its possible
      contribution to the inhibitory effect of different insulin secretagogues.
AB  - This work was undertaken in an attempt to elucidate the possible mechanism by
      which insulin secretagogues produce a fast and transient drop in the Ca(2+)
      ATPase activity of the pancreatic islet membrane. For this purpose, the enzyme
      activity was measured in either homogenates or partially purified membranes of
      islets previously incubated under different experimental conditions. Ca(2+)
      ATPase activity measured in homogenates of islets preincubated with 8 mM glucose
      decreased significantly compared to control islets incubated with 2.8 mM glucose.
      The inhibition was also observed when the enzyme activity was measured in
      homogenates of islets preincubated with 2.8 mM glucose plus 20 mM propionic acid
      as well as with glucose 2.8 mM in a buffer equilibrated with a gas mixture of O2
      and either 12% or 30% CO2. Ca(2+)-ATPase activity decreased significantly in
      partially purified islet membranes preincubated for 3 min with glucose (2 and 8
      mM), 15 mM KCl and 2 mM tolbutamide. These substances did not affect the Ca(2+)
      ATPase activity when added directly to the enzyme assay medium. The enzyme
      activity also decreased when measured in membranes preincubated at pH 6.5. The
      addition of 1 mM ATP to the preincubation medium protected the Ca(2+)-ATPase
      activity from the inhibition induced by glucose, KCl and tolbutamide as well as
      from the one produced by acidic pH in the medium. On account of these results, we
      suggest that insulin secretagogues, as well as either acidification of B-cell
      cytosol or islet membrane incubation medium, produce changes at the islet
      membrane level which promote a decrease in the Ca(2+)-ATPase activity. A shift of
      the E1-E2 equilibrium of the phosphoenzyme towards E1 may account for such
      decreased activity. Changes in Ca(2+)-ATPase activity could either favour the
      decrease or the increase in the cytosolic concentration of Ca2+ in B-cells.
      Therefore, negative and positive modulation of its activity might allow Ca(2+)
      ATPase to play a role in the switch-on and -off mechanism for intracellular Ca2+
      signal regulation of B-cell secretion of insulin.

PMID- 8574772
TI  - Decrease of body temperature in armadillos experimentally covered by soil.
AB  - The armadillo Chaetophractus villosus does not stop breathing when experimentally
      covered with soil. Under that condition, there is a gradual but considerable drop
      in deep rectal temperature (TB): after 90 minutes, mean +/- SD = 1.7 +/- 0.4
      degrees C (n = 8). As soon as the soil is removed and the animal breathes open
      air, TB gradually increases.

PMID- 8574773
TI  - [Parathyroid hormone related peptide (PTHrP) and bone metabolism].
AB  - The discovery of PTHrP was the result of research on the mechanisms by which some
      cancers cause hypercalcemia (humoral hypercalcemia of malignancy) without
      necessarily metastasizing to bone. PTHrP is also present in various normal adult
      and fetal tissues. Its concentration is normally very low (picomolar) in blood,
      but it is more abundant in milk (nanomolar concentration). PTHrP seems able to
      exert autocrine/paracrine as well as endocrine effects on bone metabolism. A
      major role for PTHrP in regulation of fetal bone metabolism has been demonstrated
      in mice. Homologous recombination has been used in these rodents to remove the
      major coding exon from one copy of the mouse PTHrP gene in embryonic stem cells.
      Subsequently generated chimeric mice transmit the mutant PTHrP allele through the
      germline. Homozygous mutants died immediately after birth and had a multitude of
      skeletal abnormalities. So PTHrP seems necessary to embryonic development of the
      skeleton. PTHrP (1-34), like PTH (1-34) fragments, might be responsible for both
      bone resorption and formation. Although the effects of the carboxyl-terminal
      fragments are still controversial, PTHrP (107-111) fragment seems able to inhibit
      osteoclast activity. PTHrP (1-34), whose 8 of the first 13 amino-acids are
      identical with those in PTH (1-34), acts through the same receptor as PTH on
      osteoblasts and renal cells membrane. The PTHrP/PTH receptor sequence is now well
      established. PTHrP-receptor coupling is mediated by cyclic AMP and/or inositols
      phosphate. The consequent activation of protein kinase A and intracellular
      calcium or protein kinase C, respectively, locally induces growth factors or
      cytokines secretion, responsible for the observed effects. The role of PTHrP
      appears important during pregnancy and lactation, when it stimulates fetal bone
      growth by increasing calcium transport from the dam to its fetus and maternal
      bone resorption allowing calcium supply for milk production, respectively. Such a
      role would be particularly important in domestic ruminants, which are often
      simultaneously pregnant and lactating. The role of PTHrP during aging (especially
      in post-menopausal women in which bone loss may induce osteoporosis) remains
      unknown and might be of peculiar interest since PTHrP (1-34) and (107-111) are
      able to restore bone loss induced by ovariectomy in rats.

PMID- 8574774
TI  - Intestinal alkaline phosphatase can transphosphorylate thiamin to thiamin
      monophosphate during intestinal transport in the rat.
AB  - Intestinal alkaline phosphatase (IAP) purified from calf intestine and IAP
      present in the brush border membrane of rat small intestine effectively
      transphosphorylated thiamin (T) to thiamin monophosphate (TMP) using Na2-beta
      glycerophosphate or Na2-creatine phosphate as phosphate donors at pH 8.5. TMP
      production in the brush border membrane was very small and corresponded to 0.001
      0.01 percent of the total inorganic phosphate simultaneously released by the
      enzyme activity. This reaction, however, could account for TMP formation
      independently from that much more important due to the hydrolysis of thiamin
      pyrophosphate during T intestinal absorption.

PMID- 8574775
TI  - Inhibition of microsomal chemiluminescence by cytosolic fractions containing
      fatty acid binding protein.
AB  - Studies were carried out to determine the relationship between Fe(++)-ascorbate
      initiated chemiluminescence and lipid peroxidation in rat liver, lung, kidney and
      brain microsomes. In order to follow the time course of membrane lipid
      peroxidation, we measured simultaneously physical and biochemical changes. Thus
      we determined the fatty acid composition of microsomal membranes from those
      tissues after peroxidation with and without ascorbic acid. Fractionation of
      cytosolic proteins with ammonium sulfate 70% saturation yielded a soluble
      fraction (enriched in fatty acid binding protein) that inhibited ascorbate-Fe++
      dependent lipid peroxidation. The inhibitory effect was concentration dependent
      and was not abolished by heating of the soluble fraction during 5 min at 100
      degrees C. Preparations from kidney, lung, heart and brain showed similar effect
      on lipid peroxidation of liver microsomal membranes. It is especulated that
      retinyl esters bound to fatty acid binding protein may act as antioxidants
      against lipid peroxidation.

PMID- 8574777
TI  - Bradycardia in armadillos experimentally covered with soil.
AB  - Chaetophractus villosus is able to maintain efficient respiratory movements when
      its nostrils are experimentally covered with soil. Under these conditions, a
      progressive bradycardia develops. It would depend on hypothermia and asphyxia.

PMID- 8574776
TI  - Beneficial effects of oxfenicine on the hypoxic rat atria.
AB  - During hypoxia the isolated rat atria released lactate into the bathing medium
      and underwent a rise of resting tension and a decline of the peak developed
      tension and pacemaker frequency. The atria from 24 h fasted rats, which oxidize
      faster their endogenous triacylglycerol pool, showed greater functional
      disturbances during hypoxia and a smaller recovery after reoxygenation than those
      from fed rats. Oxfenicine, which is a selective inhibitor of carnitine
      palmitoyltransferase I, attenuated the rise of resting tension and improved the
      post-hypoxic recovery of peak tension in the atria from fasted rats. The decline
      of the pacemaker frequency as well as the lactate output were not altered by the
      inhibitor. Present data show that oxfenicine ameliorated some of the hypoxic
      functional disturbances. Inasmuch lactate output did not change and these effects
      manifested only in the atria predisposed to the utilization of endogenous lipids,
      it may be inferred that oxfenicine preserved the atrial functions through the
      inhibition of fatty acid oxidation.

PMID- 8574778
TI  - Effects of atrial natriuretic factor on norepinephrine release evoked by
      angiotensins II and III in the rat adrenal medulla.
AB  - Atrial natriuretic factor (ANF) effects on neuronal norepinephrine (NE) release
      evoked by angiotensin II (ANG II) or angiotensin III (ANG III) were studied in
      the rat adrenal medulla. ANF 10 nM diminished the increase of NE release induced
      by ANG II (1 microM), ANG III (1 microM) or 100 mM KCl. When 10 nM ANF was added
      to the medium containing KCl plus ANG II or KCl plus ANG III, the reduction of 3H
      NE output by ANF was greater than when the atrial factor was added to the medium
      containing only ANG II or ANG III. Since both ANG II and ANG III have a
      physiological role on catecholamine metabolism, these peptides could modulate the
      adrenal medulla functions. ANG II and ANG III enhance NE release and decrease NE
      uptake in the rat adrenal medulla. Present results show that ANF is a
      physiological antagonist of both ANG II and ANG III, in the process of NE
      secretion. The interaction between ANF and the renin-angiotensin system could
      contribute to the regulation of the adrenal medulla catecholamines pathway and
      sympathetic activity.

PMID- 8574779
TI  - Electrophysiological and iontophoretic aspects of the habenular influence on
      hippocampal neurones.
AB  - In previous experimental studies, carried out on cats, we demonstrated that
      electrical stimulation of lateral habenula (LH) at 0.5-3.0 Hz or 5-20 Hz had a
      double effect (low frequency-excitation; high frequency-inhibition) on the
      spontaneous firing rate of single hippocampal neurones. Our results, in agreement
      with similar case studies, allowed us to hypothesise that in the habenular
      modulation of the hippocampus the raphe nucleus is probably involved. In fact,
      all the effects of LH stimulation were antagonised by the iontophoretic
      intrahippocampal application of methysergide. In the present series of
      experiments, performed on rats, it was possible to demonstrate that LH
      stimulation at 1-10 Hz causes an excitation of a progressively major number of
      hippocampal neurones depending upon the increase of frequency stimulation. The
      absence of habenulo-induced effects after a iontophoretic application of
      methysergide on single hippocampal units suggests the involvement of the raphe
      nucleus. Furthermore, in consideration of recent anatomical evidences
      demonstrating an excitatory projection between LH and raphe nucleus, intraraphal
      N-methyl-D-aspartate (NMDA) application, performed through a Hamilton
      microsyringe, induces an inhibitory effect. All the results suggest that in the
      raphe context it is possible to hypothesise the presence of an intrinsic
      interneurone, directly activated by the excitatory projection arising from the
      LH; this interneurone is likely inhibitory on the serotonergic raphe-hippocampus
      efferent neurone. This functional organization is responsible for the effect of
      LH stimulation at different frequencies as well as for the effects of intraraphal
      NMDA application.

PMID- 8574780
TI  - A test to approach maximal lactate steady-state in 12-year old boys and girls.
AB  - The purpose of this study was to measure the running velocity corresponding to
      the individual maximal lactate steady-state of a group of 12-year old boys and
      girls on a treadmill. This running velocity (v MLST) was compared with the
      maximal aerobic running velocity (v a max) at which maximal oxygen uptake (VO2
      max) occurs. Thirteen pupils of the same school whose puberal maturation
      corresponded to the end of stage 2 and the beginning of stage 3 of Tanner: 6 boys
      (12.2 years old +/- 0.5, 38.4 +/- 2 kg, 150 +/- 4.8 cm: group 1) and 7 girls
      (12.3 years old +/- 0.5, 37.6 +/- 6 kg, 151.4 +/- 5.6 cm: group 2) carried out
      two tests at one week interval. The first test was a maximal incremental test for
      the determination of VO2 max with Douglas's bag method and v a max. The purpose
      of the second test was the determination of maximal lactate steadystate velocity
      (v MLST) With two stages of ten minutes at 60 +/- 5% and 74 +/- 4.5% v a max
      separated by 40 minutes of complete rest (Billat, 1992); VO2max and v a max were
      significantly different, equal to 49.4 +/- 7 ml.min-1.kg-1, 40.4 +/- 4.7 ml.min
      1.kg-1 and 12.6 +/- 0.2 km.h-1, 11.2 +/- 1.2 km.h-1 for group 1 and 2
      respectively (P < 0.05). Moreover, maximal lactate steady state velocity (v MLST)
      was respectively equal to 64.8 +/- 12.5% and 64.6% +/- 12.5% VO2 max
      respectively, representing 67.8 +/- 6.2% and 68.8% +/- 8.3% v a max and was not
      significantly different for group 1 and 2. In conclusion, this study shows that
      maximal lactate steady-state velocity is not significantly different between
      young boys and girls of 12 years old, when expressed in fraction of VO2 max or v
      a max. However, VO2 max and v a max were significantly higher in boys: +27.2 and
      +11.6% higher respectively.

PMID- 8574782
TI  - [Lateral efferent system and evoked auditory potentials. Response in tinnitus].
AB  - The effects of ipsi- or contralateral masking have been studied in 45 normal
      hearing subjects and in 49 tinnitus patients. With normal subjects, ipsilateral
      masking during auditory stimulation involves--in opposition to contralateral
      masking which does not alter any latencies--a significant lengthening of all the
      latencies in the brainstem, except that of the first wave (right and left), and a
      significant decreasing of the amplitudes of the waves I L and R. It was important
      to know whether the lengthening of the latencies in the brainstem--which we
      suppose to be due to the stimulation of the lateral efferent system--was not in
      fact due to a preferential stimulation of the auditory cells from the basis of
      the cochlea. Yet experiments have shown that continuous masking of 40 dB at 750
      Hz or 4000 Hz added to stimulation, involved no significant modification of the
      latencies in normal subjects. Therefore the lengthening of the latencies obtained
      with white noise masking, belonged to an other sphere. The second problem
      concerned the responses of tinnitus patients. Ipsilateral masking in white noises
      does not alter any latencies in the patients' brainstem. They seem to have lost
      the possibility of reacting to any additional noise coming from the outside. As
      we have already noticed, their latencies before masking were different from those
      of normal subjects. With masking the patients, latencies remained unchanged
      whereas the latencies of normal subjects lengthened and caught up the patients.
      To conclude, we suppose the lateral efferent system can be explored by the
      adjunction of white noise masking, ipsilateral to the stimulation. The expected
      response is a lengthening of interpeak I-V latency, without any modification of
      the latency of the first wave. Tinnitus patients generally do not have that type
      of response to white noise masking. Their lateral efferent system may not be
      operating.

PMID- 8574781
TI  - Modulatory mechanism of ACTH on insulin secretion: effect on cytosolic Ca2+,
      membrane potential and Ca(2+-ATPase activity.
AB  - The aim of this work was to get some insight into the mechanism by which ACTH
      produces its enhancing effect on glucose-induced insulin secretion. For this
      purpose we have determined: a) the release of insulin by isolated rat islets
      incubated with 3.3 or 16.6 mM glucose with or without the addition of 500 pg/ml
      ACTH, together with the changes induced by ACTH on b) cytosolic [Ca2+] of
      isolated B cells, c) islet plasma membrane Ca(2+)-ATPase activity and d) changes
      in membrane potential of single mouse islets. ACTH significantly enhanced the
      release of insulin elicited by either 3.3 or 16.6 mM glucose. This hormone
      concentration also induced a significant increase in the cytosolic [Ca2+] in
      isolated B cells. ACTH did not produce B cell membrane depolarization.
      Conversely, ACTH produced a significant decrease in islet plasma membrane Ca(2+)
      ATPase activity. These results suggest that ACTH in concentrations similar to
      those attained by the endogenous peptide at the islet interstitium exerts its
      positive modulation on glucose-induced secretion of insulin, at least partly
      through its increasing effect on cytosolic [Ca2+] of B cells. The latter might be
      the consequence of the decreasing effect of ACTH on Ca(2+)-ATPase activity rather
      than to stimulation of voltage-dependent Ca(2+)-channels.

PMID- 8574783
TI  - Effect of felodipine on systemic hemodynamics of spontaneous mild-hypertensive
      aged rats.
AB  - The aim of the present study was to examine the effects of felodipine, a
      dihydropyridinic calcium ions channels blocker, on mean arterial blood pressure
      (MAP), cardiac output (CO), peripheral resistances (TPR) and blood flow
      distribution in spontaneously mildly hypertensive female Wistar 30-34 months old
      rats. Under pentobarbital anesthesia, CO and regional organ blood flow were
      measured by the radioactive microspheres method, before and 30 min after
      administration of felodipine 0.5 mumol/kg b. w. by gastric gavage. They were
      compared to the corresponding values in normotensive rats of the same strain and
      age. Fifteen (from twenty five) rats were hypertensive with a MAP averaging 139
      +/- 2 mm Hg. CO and TPR were slightly higher in these hypertensive rats. Cerebral
      blood flow (CBF) was lower, though the difference did not reach significant
      values. MAP significantly decreased after felodipine with no significant changes
      in CO and TPR in hypertensive as well as in normotensive animals. Renal blood
      flow (RBF) was similar before and after felodipine which significantly decreased
      renal vascular resistance in both groups. Felodipine administration did not
      induce significant changes in CBF but a significant increase in portal venous
      inflow (PVI) in hypertensive rats only. In conclusion, in old female rats with
      mild spontaneously hypertension, acute felodipine oral administration reduced
      arterial blood pressure without diminishing CBF.

PMID- 8574784
TI  - Foreign anion substitution for chloride in neonatal human red cells. Effect on
      cellular volume.
AB  - The effect of replacement of chloride by thiocyanate has been investigated in
      neonatal human red cells. On incubating these cells in isotonic SCN- medium, a
      rapid cellular swelling was observed, which was not evident in Cl- media.
      Incubation in hypertonic SCN- medium showed a rapid osmotic shrinkage followed by
      reswelling back to the initial volume. This regulatory volume increase was
      completed in a shorter time than in Cl- medium. Whole water accumulated by the
      cells in both experimental conditions can be accounted for by net Na+ uptake
      (twofold augmentation with respect to initial value). Amiloride inhibits
      specifically both cellular swelling and the Na+ content increase in these
      experimental conditions. Similar experiments in neonatal red cells incubated in
      NO3- media, as well as in adult red cells placed in NO3- or SCN- media, did not
      exhibit the same response. The findings suggest that the response of neonatal red
      cells in a SCN- containing media was mediated by activation of a Na+/H+ antiport
      mechanism.

PMID- 8574785
TI  - Redistribution of portal venous but not hepatic arterial flow is induced by
      hepatic nerve stimulation in the perfused rat liver.
AB  - The effects of hepatic nerve stimulation, norepinephrine and 6-hydroxydopamine (6
      OHDA) on hepatic hemodynamics were investigated in rat livers perfused in situ
      via both the portal vein and hepatic artery. Nerve stimulation caused a
      significant fall in total liver blood flow and an increase in portal and arterial
      pressures. Norepinephrine and 6-OHDA in addition to causing a fall in flow caused
      significant pressure increases in the bed perfused (arterial or portal). Under
      basal conditions, the inter- and intra-lobar distribution of microspheres (113Sn-
      or 57Co-labelled) introduced via the portal vein or via the hepatic artery was
      homogeneous in all 6 liver lobes. During nerve stimulation, homogeneity of
      interlobular microsphere distribution was maintained. However, the intralobar
      distribution of microspheres introduced via the portal vein displayed a
      significant redistribution from the periphery to the core of each of the four
      largest lobes studied (p < 0.05). In contrast, when microspheres were introduced
      via the hepatic artery, there was no universal redistribution of microspheres
      with only one lobe demonstrating a significant decrease in flow to the periphery
      (p > 0.05). Infusion of norepinephrine (10(-8) M) or 6-OHDA (1 mg.kg-1 body
      weight) via either the hepatic artery or the portal vein was without effect on
      the intrahepatic distribution of the microspheres. We conclude from our results
      that during hepatic nerve stimulation there is a significant redistribution of
      portal venous but not hepatic arterial flow from the periphery to the core of the
      liver lobe. The persistence of hepatic arterial flow during nerve stimulation may
      represent a protective mechanism by which the periphery of the liver, especially
      the bile ducts, remains perfused during a reduction in total liver blood flow.

PMID- 8574786
TI  - Ephemerally expressed wild-type and mutant steroid hormone receptors are equally
      able to influence expression of transient or resident templates.
AB  - We have tested transiently expressed mutant and chimeric glucocorticoid receptors
      (GR) for their ability to influence transcription of either a co-transfected or a
      stably integrated reporter gene. To the latter purpose we have generated a cell
      line harbouring 2 chromosomally anchored copies of the well-characterized mouse
      mammary tumor virus (MMTV) promoter/enhancer region fused to the bacterial beta
      galactosidase gene (LacZ). We were particularly interested in verifying whether
      some earlier characterized dominant negative GR mutants would still act the same
      way on chromosomal targets. We show that trans-regulation (activation/
      repression) of the chromosomally anchored reporter is qualitatively and
      quantitatively indistinguishable from trans-regulation obtained with transient co
      transfection. In parallel, we also tested ephemerally expressed wild-type
      progesterone receptor (PR) and androgen receptor (AR) for their capacity of
      acting on either transient or resident MMTV reporter templates. Also in this case
      we show that activation of chromosomally anchored or transiently co-transfected
      reporter by both these steroid hormone receptors is qualitatively and
      quantitatively indistinguishable. These results outline that newly expressed
      trans-effectors may exert their specific function independently of the precise
      structural organization of their responsive genes.

PMID- 8574787
TI  - wingless and DWnt4, 2 Drosophila Wnt genes, have related expression, regulation
      and function during the embryonic development.
AB  - The multigenic Wnt family encode secreted signalling molecules with important
      regulatory functions in various developmental processes. This paper reports an
      analysis of the relationships, in terms of structure, expression and function,
      that exist between the Drosophila genes wingless, the orthologue of the mammalian
      Wnt1 proto-oncogene, and DWnt4, a new member of the Wnt family. The 2 genes are
      physically clustered, are transcribed in overlapping embryonic territories under
      the control of the same regulatory molecules. Co-expression and co-regulation
      suggest first, that the close physical linkage results from the sharing of cis
      control elements and second, that the 2 Wnt signals cooperate in developmental
      patterning events. Antisense RNA experiments revealed that signalling by DWnt4 is
      essential for cells from the anterior compartment of each parasegment to adopt a
      denticled fate. We propose that wingless and DWnt4 achieve opposite, but
      complementary functions in intrasegmental cell patterning of the embryonic
      ectoderm.

PMID- 8574788
TI  - Ovarian production of IL6 and its potential inhibitory effect on progesterone
      secretion in Cynomolgus fascicularis.
AB  - We explored the potential relevance of interleukin-6 (IL6) to ovarian function in
      cynomolgus monkey females which were treated to induce multiple follicular
      growth. Present work gave evidences that IL6 was produced in the ovulatory
      follicle after hCG administration by using anti-IL6 monoclonal antibody and
      immunohistochemical techniques. IL6 was produced by granulosa cells in cultures.
      However, this production was not stimulated by adding to cultures FSH or Bt2cAMP,
      known to induce IL6 production in various cell types. IL6 was shown to antagonize
      luteinizing FSH effects. Inhibitory IL6 effect was probably mediated at a site
      distal to cAMP generation since it had no effect on progesterone production
      induced by dibutyryl cAMP treatment. The presence of IL6 in the ovulatory
      follicle show that inflammatory cytokines may play a role at ovulation. On the
      other hand, its inhibitory effect on progesterone production by granulosa cells
      could not likely affect the process of luteinization which is controlled by
      LH/hCG.

PMID- 8574789
TI  - Fusion of the LAZ3/BCL6 and BOB1/OBF1 genes by t(3; 11) (q27; q23) chromosomal
      translocation.
AB  - The LAZ3/BCL6 gene on chromosome 3q27 is recurrently disrupted in B-cell non
      Hodgkin's lymphomas by translocations involving immunoglobulin genes or other
      chromosome regions. We have studied the t(3; 11) (q27; q23) translocation,
      present in a B-cell leukemia cell line (Karpas 231). As a consequence of this
      translocation, a LAZ3 chimeric transcript was created by fusion, 5' to the LAZ3
      exon 2, with a transcribed sequence identical to BOB1/OBF1, a B cell-specific
      coactivator of octamer-binding transcription factors, recently described.
      Nucleotidic sequence of a nearly full-length cDNA of the BOB1/OBF1 gene revealed
      particular features in the 3' untranslated region of the gene, including
      pyrimidine-rich sequence repeats, an Alu motif, and a polymorphic [CCTT]
      tetranucleotide microsatellite. Two A to G transition mutations were also
      detected in the coding region of one allele of a lymphoma B-cell line, Raji,
      leading to 2 amino-acid changes in the C-terminal region. Due to its cell
      specificity and role as a coactivating transcription factor, chromosomal
      translocation and/or perhaps point mutation of BOB1/OBF1 may contribute to B cell
      tumorigenesis.

PMID- 8574790
TI  - Activity of the rat lactase gene promoter in transfected human colon cancer
      cells.
AB  - The promoter activity of the upstream region of the rat small intestinal lactase
      phlorizin hydrolase gene has been analysed by transfection in the human colon
      cancer cell line Caco-2. A 0.9 kb mRNA, corresponding to the CAT reporter gene,
      was synthesized from the transcription start site of the LPH gene. The rate of
      expression, determined by semi-quantitative RT-PCR, was very low, and depended on
      the length of the promoter fragment in front of the reporter gene. By
      immunocytology, we found that the low level of expression resulted from the low
      number of cells (about 1%) in which CAT was produced. The endogenous lactase was
      present in 10-20% of the cells in culture, and evidence is provided that most
      cells that expressed CAT did not co-express the endogenous lactase. We conclude
      from this study that the rat small intestinal LPH gene promoter is active in the
      human Caco-2 colon cancer cells. Hence Caco-2 cells constitute an in vitro model
      to analyse the basic molecular mechanisms involved in the gene transcription of
      intestinal digestive enzymes. Yet, the mosaic expression of the endogenous
      lactase and of the reporter gene under the control of the rat LPH gene promoter,
      suggests that Caco-2 cells may present specific regulatory mechanisms of
      expression of small intestinal enzymes, possibly in relation to their tumourous
      origin.

PMID- 8574791
TI  - Use of annexin V-ferrofluid to enumerate erythrocytes damaged in various
      pathologies or during storage in vitro.
AB  - Recombinant human annexin V was bound covalently to 9 nm maghemite (gamma Fe2O3)
      nanoparticles, yielding annexin-ferrofluid (AnxFF), and used to separate annexin
      bound red blood cells (RBC) in a magnetic field and estimate their percentage in
      various bloods. Annexin binding in normal human RBC increased proportionately
      with storage from 8% on day 2 to 42% on day 100. Enhanced AnxFF binding was
      associated with various pathologies. Thus, normal blood contained 10.7 +/- 5.9%
      AnxFF binding RBC; bloods with normal sedimentation rates (albeit with some
      disease necessitating analysis) contained 23.5 +/- 6.2%; those with high
      sedimentation rates contained 51.5 +/- 12.3%; sickle cell anaemia patients' blood
      contained 50.0 +/- 9.3%, and bloods from patients with other pathologies
      (deforming rheumatic disease, cancer necessitating chemotherapy, etc.) contained
      58.6 +/- 7.6% AnxFF binding RBC. Enhanced Ca+2-dependent annexin binding reflects
      a loss of the asymmetric distribution of anionic phospholipids in plasma
      membranes which may constitute a signal for the destruction of the modified cells
      by the reticuloendothelial system. Once these preliminary results are confirmed,
      the determination of the fraction of AnxFF bound erythrocytes, following their
      magnetic separation, could prove a simple and rapid quality test for example in
      the context of blood transfusion.

PMID- 8574792
TI  - Cancer: the translation of advances in basic science to human therapy. 22-27 July
      1995. La fondation des Treilles, Tourtour France.

PMID- 8574793
TI  - Sexuality: a cultural diversity issue.

PMID- 8574795
TI  - Nursing databases. Interview by Marie Manthey.

PMID- 8574794
TI  - Memoir from a new American.

PMID- 8574797
TI  - Toward a more diverse profession.

PMID- 8574796
TI  - Values for a new millennium.

PMID- 8574798
TI  - How one collaboration opened doors to diversity.

PMID- 8574799
TI  - Problems with the healthcare system as experienced by people of color.

PMID- 8574800
TI  - Cultural diversity in care: the cultural assessment.

PMID- 8574801
TI  - Mentoring and the cultural perspective.

PMID- 8574802
TI  - Indium-111 octreotide in Graves' disease and in the evaluation of active
      exophthalmos.
AB  - Thyroid Associated Ophthalmopathy (TAO) is an autoimmune disorder generally
      associated with Graves' disease (GD). The aim of our study was to evaluate the
      uptake of indium-111 Octreotide (111In-OCT), a somatostatin (SS) analogue able to
      bind specific SS receptors, at the level of the thyroid and orbits in patients
      with TAO. Seven patients with exophthalmos were investigated: six had GD while
      one was affected with a non small cell lung cancer (NSCLC). One patient with GD
      had undergone total thyroidectomy (TT) for a thyroid cancer. At the time of the
      study two patients were hyperthyroid, four were euthyroid and one was
      hypothyroid. 111 MBq of 111In-OCT were i.v. injected and two 30-minute scans were
      performed at 4 and 24 hours; 5 minute planar images were also obtained at 25, 60
      and 120 minutes. A 180 degrees SPECT was carried out 5 hours after the injection
      in one patient. A qualitative analysis was performed, comparing these images with
      those obtained in 7 control patients without thyroid illness or exophthalmos.
      Moreover, in the TAO patients thyroid, orbit and brain counts were evaluated in
      comparison with background (BK) and blood activity (BA), measured at the level of
      the venous longitudinal sinus. In GD intense thyroid uptake was demonstrated
      independently of the functional state, with highest ratio compared to BK seen at
      24 hours. Low uptake in the patient with NSCLC, no activity in the patient with
      GD that underwent TT, and slight or absent thyroid uptake in the controls were
      observed. Intense uptake was seen in the orbits of the patient who clinically had
      the most severe ophthalmopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574803
TI  - Usefulness of 99mTc-MIBI stress myocardial SPECT bull's-eye quantification in
      coronary artery disease.
AB  - 99mTc-methoxy-isobutyl isonitrile (MIBI) myocardial SPECT quantification
      performed using a Bull's-eye polar map, was evaluated and compared with visual
      analysis in 120 patients with proven or suspected CAD. The study series comprised
      106 men and 14 women, age 37-75 years (mean 51 +/- 6), 68 of whom had had a prior
      myocardial infarction. Coronary angiography was taken as the gold standard: one
      vessel disease was present in 24 patients, two-vessel disease in 39, and three
      vessel disease in 44, whereas no significant stenosis was documented in 13 cases.
      Forty age-matched subjects (26 men, 14 women), with less than a 5% chance of
      having CAD, were enrolled to establish the normal database for males and females.
      ROC analysis was used to calculate the optimal thresholds for the definition of
      the disease extension in each vascular territory of the Bull's-eye polar map: 10%
      for LAD, 8% for LCX, and 20% for RCA territory. The sensitivity/specificity ratio
      of the scintigraphy was: 75/82% with the visual and 78/74% with the quantitative
      analysis for LAD; 60/90% with visual and 72/64% with visual and 70/62% with
      quantitative analysis for RCA territory. The sensitivity/specificity ratios for
      the CAD diagnosis were similar with the visual and the Bull's-eye analysis in
      92/61% and 93/61% respectively. Bull's-eye analysis agreed with visual analysis
      in 296/360 vessels. Two and three-vessel disease were most frequently observed
      using the Bull's-eye approach.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574804
TI  - Follicular thyroid carcinoma and mediastinal goiter in a case of situs inversus
      viscerum.
AB  - A 55-year-old woman with total situs inversus viscerum was subjected to total
      thyroidectomy for a well-differentiated follicular thyroid carcinoma. After
      surgery the patient remained euthyroid for two months and serum TSH did not rise.
      A whole body scan with iodine-131 (131I) showed mediastinal uptake. A chest
      computed tomography visualized a sequestered substernal goiter. Upon the
      patient's refusal to undergo surgery, she was treated with 150 mCi of 131I. A
      further dose of 100 mCi of 131I was administered six months later. Ten years
      after treatment, the patient is still alive and disease-free.

PMID- 8574805
TI  - Diffuse bone marrow uptake [123I]MIBG in neuroblastoma: an "MIBG super scan" case
      report.
AB  - We present the case of a 3-year-old child with neuroblastoma metastatic to the
      bone marrow. [123I]MIBG total body scintigraphy revealed a diffuse pattern of
      intense fixation throughout the skeleton. This was analogous to the "super scan"
      described with 99mTc-MDP bone scintigraphy when extensive metastatic or metabolic
      bone disease is present. Essentially, a high bone-to-soft tissue ratio was found
      without uptake in the liver, kidney and bladder, owing to a "steal" mechanism
      caused by the avid bone metastases.

PMID- 8574806
TI  - Differences between accumulation of 99mTc-MIBI and 201Tl-thallous chloride in
      tumour cells: role of P-glycoprotein.
AB  - Both 99mTc-MIBI and 201Tl have been used for tumour imaging. It has recently been
      reported that 99mTc-MIBI is a substrate for P-glycoprotein (Pgp), a membrane pump
      which mediates multidrug resistance. We have evaluated the role of Pgp in the
      cellular accumulation of 201Tl by using sensitive and resistant strains of
      Chinese hamster ovary (CHO) fibroblasts (AuxB1 and CHRC5, respectively) grown in
      suspension culture. 201Tl accumulation was the same in sensitive and resistant
      cells, whereas 99mTc-MIBI accumulation was much lower in resistant cells than in
      sensitive ones. Down-modulation of Pgp with 100 microM verapamil did not alter
      cellular accumulation of 201Tl while it significantly increased 99mTc-MIBI
      accumulation in both types of cell. Similarly, 10 microM verapamil did not affect
      the rate of washout of 201Tl from preloaded cells, while 99mTc-MIBI washout was
      greatly reduced in the presence of verapamil. These results suggest that 201Tl
      will accumulate in both sensitive and resistant tumour cells, whereas 99mTc-MIBI
      will be extruded from resistant cells and therefore may be less useful for tumour
      detection when the tumour cells express high Pgp levels.

PMID- 8574807
TI  - pI-dependent isolation of antibody isoforms by semipreparative isoelectric
      focusing.
AB  - A procedure based on isoelectric point (pI) was developed to separate
      immunoreactive antibody isoforms. A polyclonal IgG, rabbit anti-human serum
      albumin (R-HSA), was subjected to free-flow isoelectrophoresis using a
      semipreparative isoelectric focusing apparatus that fractionates proteins by pI.
      Twenty fractions were collected and their pH, protein content, and
      immunoreactivity determined. The development of a pH gradient and separation of
      proteins took place within 3 hours with about 93% protein recovery. The protein
      concentration of the individual fractions varied. Isoelectric focusing of
      fractions in agarose slab gels confirmed the clear separation of antibody
      isoforms. Enzyme-linked immunosorbent assay demonstrated significantly higher
      immunoreactivity (P < or = 0.03) of the majority of the antibody isoform
      fractions compared with native R-HSA IgG. The procedure is capable of isolating
      immunoreactive antibody isoform fractions from immunologically irrelevant and low
      affinity antibodies.

PMID- 8574808
TI  - The stimulatory effect on human erythrocyte rubidium-86 uptake by anti-cardiac
      glycoside antibodies.
AB  - Considerable, but as yet still controversial evidence indicates the presence, in
      mammalian tissues of endogenous digitalis-like factors (EDLFs) which inhibit cell
      membrane Na+, K(+)-adenosine triphosphatase (Na+, K(+)-ATPase) and which may
      cross-react with anti-digitalis antibodies. The aim of this study was to evaluate
      the effect of antibodies against cardiac glycosides on Na+, K(+)-ATPase in human
      erythrocytes. For this purpose, we measured the effect of antibodies against two
      different cardiac glycosides (anti-ouabain rabbit antiserum and anti-digoxin Fab
      fragments) on the activity of the Na+, K(+)-ATPase, as measured by erythrocyte
      rubidium-86 (86Rb) uptake, in subjects who had never come into contact with
      exogenous cardiac glycosides, and compared these results with the effect of two
      control rabbit sera: a normal serum and an antiserum to a non-related antigen.
      Anti-ouabain rabbit antiserum and anti-digoxin Fab fragments induced a
      significantly greater percentage change in 86Rb uptake in the erythrocytes than
      the two control sera (ANOVA followed by multiple comparison by the Games-Howell
      test). The average percentage change was +11.8 +/- 16.3% (n = 19) (mean +/- SD)
      for anti-ouabain antiserum +10.8 +/- 15.6% (n = 23) for anti-digoxin Fab
      fragments, -1.68 +/- 11.2% (n = 11) for anti-rhGM-CSF antiserum, and -5.8 +/-
      11.7 (n = 10) for normal control serum. In a subgroup of ten subjects in whom the
      3 antisera were tested simultaneously, the stimulation of erythrocyte 86Rb uptake
      induced by the two antidigitalis antibodies correlated significantly (r = 0.906,
      p = 0.001, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574809
TI  - Evaluation of the response to chemotherapy in patients affected with small cell
      lung cancer using discriminant analysis: a preliminary report.
AB  - This report represents an attempt to combine the serum levels of more tumor
      markers together to evaluate the response to chemotherapy in 26 patients affected
      with small cell lung cancer (SCLC), by means of discriminant analysis. A pilot
      prospective study was performed on 26 subjects affected with inoperable SCLC (18
      extensive diseases, and 8 limited diseases) and treated with chemotherapy
      (etoposide plus cisplatin regimen). Serum levels of a panel of tumor markers:
      Carcinoembryonic antigen (CEA), Tissue Polypeptide Antigen (TPA), Neuron Specific
      Enolase (NSE) and CYFRA -21.1 were determined before starting chemotherapy and at
      the restaging time (after 3 months). To optimize the classification power of
      these markers, a discriminant analysis was done, which permitted generating two
      classification functions, based on Tissue Polypeptide Antigen and Neuron Specific
      Enolase levels able to correctly classify 25 out of 26 subjects (8 progressions
      and 18 non progressions). The results obtained, furtherly confirm that tumor
      markers are useful to evaluate the chemotherapy response and indicate a possible
      approach to obtain the maximum usefulness of the serum marker levels.

PMID- 8574810
TI  - A new 99mTc labelling method for leucocytes: in vitro and in vivo comparison with
      99mTc-HMPAO.
AB  - A new method for the labelling of mixed leucocytes with 99mTc-tropolone was
      optimized and compared with a 99mTc-HMPAO leucocyte labelling procedure in vitro
      and in vivo. In the present study, leucocytes obtained from patients suffering
      from Crohn's disease, were isolated and labelled with 99mTc-HMPAO or labelled
      according the new 99mTc-tropolone procedure using 9.8 mM tropolone, 1 microM
      stannous chloride and 0.8 mM potassium borohydride (KBH4) at pH 5.5-6. Labelling
      efficiency with 99mTc-tropolone yielded 92 +/- 3%, which is higher compared to
      the 99mTc-HMPAO labelling procedure (64 +/- 13%) using 10(8) of leucocytes. In
      vitro stability and viability of both the tropolone and the HMPAO labelled cells
      was investigated. The viability test of the 99mTc-labelled leucocytes was
      performed in autologous plasma at 37 degrees C and compared with unlabelled
      leucocytes. After 18 hours of incubation a significant (P < 0.05) higher
      stability was observed for 99mTc-tropolone labelled leucocytes (84 +/- 5%)
      compared with that of 99mTc-HMPAO labelled leucocytes (73 +/- 5%). The viability
      of the 99mTc-labelled leucocytes observed for both labelling procedures was
      similar to unlabelled leucocytes. In vivo experiments were performed in mice.
      99mTc-tropolone or 99mTc-HMPAO labelled murine mixed leucocytes were injected in
      mice, with a Staphylococcus aureus ATCC 25923 thigh infection. Analysis of
      scintigraphic images yielded a faster clearance of the 99mTc-tropolone labelled
      leucocytes. This was most likely due to a significant (P < 0.02) higher liver
      uptake at 4 hours after administration of the 99mTc-tropolone labelled leucocytes
      (19%) in comparison with 99mTc-HMPAO labelled cells (9%). Faster and significant
      (P < 0.02) higher accumulation of the 99mTc-tropolone labelled leucocytes was
      observed at the site of infection compared with 99mTc-HMPAO labelled leucocytes
      at all time-intervals after the administration of the 99mTc-labelled leucocytes.
      The new 99mTc-tropolone leucocyte labelling procedure, offers an attractive low
      cost agent for research purposes.

PMID- 8574811
TI  - Effective radiation dose to the patient and to the general population from
      nuclear medicine procedures: variations in the last twenty-year period.
AB  - We have evaluated how changes in nuclear medicine (NM) techniques over the last
      twenty-year period have modified radiation exposure to the patient and
      population. For this purpose, we estimated the variations in the mean effective
      dose to the patient, and both the collective and the per capita effective dose to
      the population of the province of Varese, derived from radioisotope examinations
      carried out in the four NM Centers of this province in the years 1972, 1981, and
      1991. Dosimetric calculations were based on ICRP Publication 53 for most of the
      radiopharmaceuticals used, and tissue weighting factors were based on ICRP
      Publication 60. The total number of NM exams carried out was 19,744 in 1972,
      31,973 in 1981, and 23,623 in 1991. Between 1972 and 1991 there has been a
      substantial decrease in the effective irradiation to the patient and to the
      general population (mean effective dose to the patient: from 21.2 to 6 mSv; per
      capita mean effective dose: from 0.58 to 0.18 mSv), and in the per capita
      equivalent dose to some target organs, such as the thyroid (9.6-->1.5 mSv) and
      liver (0.51-->0.07 mSv). At the same time, there has been a significant increase
      in the per capita equivalent dose to the bladder (0.05-->0.48 mSv), skeleton
      (0.08-->0.36 mSv), and testes (0.02-->0.15 mSv), and a less marked increase to
      the ovaries (0.03-->0.06 mSv). The per capita equivalent dose to red marrow (0.13
      ->0.1 mSv) and to the large intestine (0.1-->0.12 mSv) did not change
      significantly.

PMID- 8574812
TI  - Comparison of concentration-time profiles of levobunolol and timolol in anterior
      and posterior ocular tissues of albino rabbits.
AB  - The potential effects of anti-glaucoma drugs, such as levobunolol and timolol, on
      blood flow in the posterior segment of the eye are of great interest in terms of
      changes in optic nerve head perfusion and prevention of visual field loss. These
      effects are related to the rate and extent of their absorption into the site of
      action. In this study, the concentrations of timolol and levobunolol in the
      aqueous humor, iris-ciliary body, vitreous humor, choroid-retina, and optic nerve
      were compared following instillation of a single drop of 0.5% ophthalmic
      solutions into albino rabbit eyes. Tissue drug and metabolite concentrations were
      measured by liquid chromatography-mass spectrometry. Dihydrobunolol (DHB) is an
      equipotent metabolite of levobunolol. In the anterior segment of the eye,
      levobunolol plus DHB concentrations were higher than timolol concentrations in
      aqueous humor and were comparable to those of timolol in iris-ciliary body.
      However, in the choroid-retina and optic nerve, timolol concentrations were
      greater than those of levobunolol plus DHB. Overall, the study demonstrates
      comparable concentrations of levobunolol and timolol in the anterior section of
      the eye. The low availability of levobunolol in the posterior segment as compared
      to timolol may be a key advantage for levobunolol in producing less adverse
      effect on blood flow in the choroid-retina and optic nerve.

PMID- 8574813
TI  - Establishment of a rabbit short-term dry eye model.
AB  - The dry eye syndrome is a chronic disease which can become a serious threat to
      useful vision. However, there is only a limited understanding regarding effective
      treatment or prevention of this disease. Establishing an effective mode of
      treatment requires the use of a satisfactory animal dry eye model. Ideally, such
      a model should rapidly determine the effectiveness of agents that inhibit the
      damaging effects of this syndrome. This paper presents a short-term dry eye model
      using rabbits, which combines mechanical prevention of blinking and methylene
      blue staining. This model is not intended to be a precise representation of the
      dry eye syndrome, since this disorder has recently become recognized to involve a
      primary pathological process of the corneal and conjunctival epithelium. However,
      by using this model, clinical signs of dry eye can be observed after a few hours
      in the form of acute desiccation. Corneal damage can easily be evaluated both
      qualitatively by methylene blue staining scores, and quantitatively by chronic
      assay. Visually observed corneal epithelial thinning was confirmed by scanning
      electron microscopy (SEM) to be due to loss of epithelial integrity. Using a 3%
      chondroitin sulfate solution, an already proven effective agent for dry eye, this
      model effectively demonstrated an 80% inhibition in the development of methylene
      blue positive lesion after a period of only 2 hours. This short term dry eye
      model is valuable in primarily screening the efficacy of potential therapeutic
      agents in the prevention and treatment of dry eye.

PMID- 8574814
TI  - Cyclosporine in collagen particles: corneal penetration and suppression of
      allograft rejection.
AB  - The purpose of this study was to determine the pharmacokinetics of cyclosporine
      in the cornea and aqueous humor following topical application in collagen
      particles and to determine the capacity of cyclosporine in collagen particles to
      suppress corneal allograft rejection. Cyclosporine was prepared for topical
      application in three vehicles: collagen particles suspended in methylcellulose,
      collagen shields, and corn oil. Rabbit eyes were treated with a single
      application of one formulation. Corneas, aqueous humor samples, and blood samples
      were collected at 2, 4, 8, 12, and 24 hours. Peak concentrations of drug were
      reached between 2 and 4 hours in the cornea and between 4 and 8 hours in the
      aqueous humor. No drug was found in the blood. Collagen particles and shields
      produced significantly higher concentrations of cyclosporine in the aqueous humor
      and cornea, compared with corn oil drops, at virtually all time points. In the
      second part of the study, rabbits with vascularized corneas underwent corneal
      transplantation and were treated with one of the formulations beginning either at
      the time of transplantation (prophylactically) or at the first sign of an
      allograft immune reaction (delayed treatment). Cyclosporine delivered in collagen
      particles was effective in preventing primary corneal allograft rejection in
      nearly all of the grafts (96%) treated prophylactically, and in 67% of the grafts
      treated when signs of the first stage (grade 1) of immune graft reaction were
      observed. Grafts treated with cyclosporine in collagen shields showed similar
      survival rates (87% and 64%, respectively), whereas only 40% of the grafts
      treated prophylactically and only one (18%) receiving delayed treatment with the
      corn oil preparation survived. These results demonstrate the efficacy of collagen
      particles for delivery of hydrophobic drugs to the ocular surface and the
      potential for preventing corneal graft rejection with topically applied
      cyclosporine in a collagen-particle vehicle.

PMID- 8574815
TI  - Pharmacodynamics of subconjunctival gentamicin after experimental cataract
      operations and traumatic lacerations.
AB  - We addressed the concern whether retinal toxicity could occur with
      subconjunctival gentamicin injections after cataract operations or traumatic
      corneoscleral lacerations. The lacerations were created along the superior limbus
      of rabbit eyes and the lenses removed. We sutured the right eyes to mimic a
      cataract operation and the left eyes remained unsutured to mimic a traumatic
      corneoscleral laceration. Vitreous humor samples were obtained at 1, 2, 4, 8 and
      12 hours after the subconjunctival injection, but in no case did vitreal
      concentration approach retinotoxic levels (> 133 micrograms/ml).

PMID- 8574816
TI  - Inhibition of polyol formation in rat lens by verapamil.
AB  - Accumulation of sorbitol and xylitol in rat lenses incubated in medium-199 with
      and without verapamil has been studied. This antihypertensive drug, known to
      attenuate hypertension by its calcium channel blocking effect, is also known to
      inhibit cataract formation in diabetes. The present studies have demonstrated
      that verapamil's effect against cataract could also be partially related to its
      aldose reductase inhibitory activity, in addition to the Ca++ channel blocking
      activity. The accumulation of sorbitol in the lenses incubated with high glucose
      in the presence of 400 microM verapamil was only 2.3 mmoles/Kg wet weight against
      11.3 mmoles/Kg in its absence. The level of xylitol attained in the presence of
      10 mM xylose was 25.7 +/- 2.4 mmoles/Kg. It decreased to 4.8 +/- 1.2 mmoles/Kg in
      presence of 400 microM verapamil. Hence, verapamil is significantly effective in
      inhibiting lens aldose reductase dependent polyol synthesis, an action
      simultaneous with its effect on calcium penetration.

PMID- 8574817
TI  - Glucocorticoid-induced cataract of developing chick embryo as a screening model
      for anticataract agents.
AB  - In order to develop an effective screening model for anticataract agents, we
      examined the age dependence of cataract induction by glucocorticoid in developing
      chick embryos. Hydrocortisone sodium succinate (0.25 mumol) was administered to
      chick embryos on day 15 (15-day-old) and cataract formation was examined 48 hr
      later. Administration earlier than on day 13 or later than on day 15 was a little
      or ineffective. These results indicate that the formation of glucocorticoid
      induced cataract in developing chick embryos depends on developing stages. The
      embryos treated with hydrocortisone sodium succinate on day 15 decreased GSH
      amount in the lens, approximately 50% of the control in 48hr. However, the
      embryos treated at other ages, in which cataract was not induced, showed little
      or no decrease of GSH. The cataract formation in chick embryos appeared to depend
      on structure of steroid and was due to biological activities of glucocorticoids.
      Since cataract is easily produced in a reproducible manner with high incidence by
      glucocorticoid, our chick embryo model will be a valuable model system for
      screening anticataract agents.

PMID- 8574818
TI  - Peroxide damage to rat lens in vitro: protective effect of dehydroascorbate.
AB  - The possible protective effect of dehydroascorbate against peroxide damage to rat
      lens under in vitro organ culture has been studied by measuring the levels of
      ATP, GSH and the uptakes of rubidium and alpha-aminoisobutyric acid. All these
      parameters were adversely affected by the presence of 0.5 mM hydrogen peroxide in
      the culture medium. Dehydroascorbate (1 mM) protected the lens against such
      effects. The protective effect is tentatively attributable to the utilization of
      peroxide in peroxidative decarboxylation of the dehydroascorbate, in a manner
      similar to that of other alpha-ketoacids.

PMID- 8574819
TI  - L-type voltage-dependent Ca2+ and ATP-sensitive K+ channels are not involved in
      the regulation of bovine ciliary muscle contractility.
AB  - We compared the effects of L-type voltage-dependent Ca2+ and ATP-sensitive K+
      channels modulators on contractility in isolated bovine ciliary muscle with those
      in rabbit aortae. Nifedipine (0.1 and 1 microM), a dihydropyridine Ca2+ channel
      blocker, did not relax bovine ciliary muscle precontracted with 100 mM KCl.
      Nondihydropyridine Ca2+ channel blockers, semotiadil fumarate (SD-3211, 1 microM)
      diltiazem (10 microM) and verapamil (1 microM), did not affect contractility, but
      at higher concentrations, they all had a relaxant effect. Bay K 8644, a L-type
      voltage-dependent Ca2+ channel activator, even at 1 microM, did not contract
      ciliary muscle partially depolarized with 10 mM KCl, whereas at 0.01 and 0.1
      microM it contracted partially depolarized rabbit aortae. Furthermore, diazoxide
      (100 microM), an ATP-sensitive K+ channel opener, had a relaxant effect on aortae
      precontracted with 25 mM KCl, but not on ciliary muscle. This relaxation was
      inhibited by glibenclamide (10 microM), an ATP-sensitive K+ channel blocker,
      indicating that diazoxide relaxes rabbit aortae by activating ATP-sensitive K+
      channels. These results suggest that L-type voltage-dependent Ca2+ and ATP
      sensitive K+ channels play a minor role in the regulation of bovine ciliary
      muscle contractility.

PMID- 8574820
TI  - Delivery of systemic regular insulin via the ocular route in cats.
AB  - Regular porcine insulin was administered as eye drops to eighty healthy,
      euglycemic cats. Insulin was applied alone and in combination with four different
      permeation enhancers. Serum glucose and insulin were monitored for four hours
      following the eye drops. Significant changes in both serum glucose and insulin
      occurred when the insulin was administered with 0.5% saponin, 0.5% Brij-78, 1% BL
      9 and 2% BL-9. Insulin delivered alone and in the presence of Brij-99 did not
      significantly alter glucose and insulin concentrations. While effective as an
      absorption enhancer, 0.5% saponin caused transient ocular irritation in all the
      test subjects. Brij-99 was also irritating to some of the cats. Solutions
      containing Brij-78 and BL-9 were well tolerated. This study demonstrated that
      short-acting insulin is systemically absorbed in cats via the ocular route when
      applied with certain emulsants.

PMID- 8574821
TI  - Systemic toxicology and laser safety of laser targeted angiography with heat
      sensitive liposomes.
AB  - Angiography is currently limited by its lack of local and tissue specificity. The
      dye rapidly fills both the retinal and choroidal vessels and leaks out of the
      vessels thus hampering visualization of small vascular beds such as occult
      choroidal neovascularization. We have developed a method of laser targeted
      delivery based on encapsulating the dye in heat sensitive liposomes,
      administering the liposomes intravenously and causing them to release their
      content by noninvasively warming the target tissue with a laser pulse delivered
      through the pupil. The local release yields a bright fluorescent bolus which
      selectively highlights retinal or choroidal vessels. A preliminary investigation
      of the potential side effects of the method is presented. In rats the systemic
      toxicity of carboxyfluorescein-entrapped liposomes was compared with that of the
      free dye. No significant difference was found between the two. Non-human primates
      exposed to repeated laser targeted angiography were monitored over time and no
      significant side effects were observed. The safety of the laser exposures was
      assessed by conventional fluorescein angiography and histopathology. Choroidal
      laser targeted angiography was achieved without damage. Retinal laser targeted
      angiography was accompanied by mild and local damage in an area remote from the
      fovea. The study indicates that laser targeted choroidal angiography can be
      performed safely and holds promise for diseases such as age related macular
      degeneration with occult choroidal neovascularization. Further improvements are
      needed to ensure that no side effects accompany retinal laser targeted
      angiography.

PMID- 8574822
TI  - Laboratory tests for detection of human immunodeficiency virus type 1 infection.

PMID- 8574823
TI  - Extracellular matrix proteins, regulators of T-cell functions in healthy and
      diseased individuals.

PMID- 8574824
TI  - Nucleocapsid protein N of Lelystad virus: expression by recombinant baculovirus,
      immunological properties, and suitability for detection of serum antibodies.
AB  - The ORF7 gene, encoding the nucleocapsid protein N of Lelystad virus (LV), was
      inserted downstream of the P10 promoter into Autographa californica nuclear
      polyhedrosis virus (baculovirus). The resulting recombinant baculovirus,
      designated bac-ORF7, expressed a 15-kDa protein in insect cells. This protein was
      similar in size to the N protein expressed by LV in CL2621 cells when it was
      analyzed on sodium dodecyl sulfate-polyacrylamide gels. The N protein expressed
      by bac-ORF7 was immunoprecipitated with anti-ORF7 was immunoprecipitated with
      anti-ORF7 peptide serum, porcine convalescent-phase anti-LV serum, and N protein
      specific monoclonal antibodies, indicating that this N protein had retained its
      native antigenic structure. The recombinant N protein was immunogenic in pigs,
      and the porcine antibodies raised against this protein recognized LV in an
      immunoperoxidase monolayer assay. However, pigs vaccinated twice with
      approximately 20 micrograms of N protein were not protected against a challenge
      with 10(5) 50% tissue culture infective doses of LV. Experimental and field sera
      directed against various European and North American isolates reacted with the N
      protein expressed by bac-ORF7 in a blocking enzyme-linked immunosorbent assay.
      Therefore, the recombinant N protein may be useful for developing diagnostic
      assays for the detection of serum antibodies directed against different isolates
      of LV.

PMID- 8574825
TI  - Nucleotide sequence analysis and seroreactivities of the 65K heat shock protein
      from Mycobacterium paratuberculosis.
AB  - Mycobacterium paratuberculosis is the causative agent of Johne's disease, a
      chronic enteritis in ruminants. It has also been implicated as a possible cause
      of Crohn's disease, an inflammatory bowel disease of unknown etiology. The
      mycobacterial 65K heat shock proteins (hsp-65K) are among the most extensively
      studied mycobacterial proteins, and their immunogenic characteristics have been
      suggested to be the basis for autoimmunization in chronic inflammatory diseases.
      In this context, we isolated and sequenced the hsp-65K-encoding gene from our M.
      paratuberculosis PTB65K genomic library. A high degree of identity was found
      between the open reading frame (ORF) of the PTB65K gene and those of
      Mycobacterium tuberculosis (89.6%), Mycobacterium leprae (86.6%), and
      Mycobacterium avium 18 (98.8%). The amino acid sequence alignment of the PTB65K
      protein with the hsp-65K homologs revealed that the M. tuberculosis and M. leprae
      proteins each differed by 36 amino acid residues and that the M. avium 18 protein
      differed by 8 residues. We also investigated the humoral immune responses of
      animals with Johne's disease and patients with Crohn's disease against the
      recombinant PTB65K antigen. Immunoblot analysis showed that sera from only 3 of
      10 clinically ill and 5 of 25 subclinically ill cows reacted with PTB65K. In
      addition, sera from two of two sheep and one of two goats with clinical symptoms
      of Johne's disease also reacted with PTB65K; 0 samples from 10 normal cows
      reacted. In humans, sera from 7 of 13 patients with Crohn's disease, 3 of 4 with
      tuberculosis, 5 of 6 with leprosy, 5 of 12 with non-inflammatory bowel disease,
      and 0 of 4 with ulcerative colitis reacted with the recombinant PTB65K antigen.
      These results indicate that this PTB65K heat shock protein is uninformative when
      used for serodiagnosis of Johne's disease in animals. However, in humans, the
      high intensity of antibody reactions of some sera from Crohn's disease patients
      compared with that from noninflammatory bowel disease patients showed a positive
      correlation with mycobacterial diseases.

PMID- 8574827
TI  - Effects of pretreatment with SDZ MRL 953, a novel immunostimulatory lipid A
      analog, on endotoxin-induced acute lung injury in guinea pigs.
AB  - SDZ MRL 953 (SDZ), a novel immunostimulatory lipid A analog, has been reported to
      have immunopharmacological activities similar to those of lipopolysaccharide
      (LPS) but to have little of the toxicity of LPS. We investigated the effects of
      pretreatment with SDZ on Escherichia coli endotoxin-induced acute lung injury in
      guinea pigs. Four experimental groups consisted of saline control (n = 16), SDZ (
      12 h) plus LPS (2 mg/kg of SDZ per kg of body weight injected intravenously 12 h
      before intravenous injection of 2 mg of LPS per kg; n = 15), SDZ (-10 min) plus
      LPS (SDZ injected 10 min before LPS injection; n = 10), and LPS alone (n = 16).
      The animals were sacrificed, and lung tissue was sampled 4 h after LPS or saline
      infusion. Lung injury was assessed by measuring the wet weight-to-dry weight
      ratio and the level of 125I-labeled albumin accumulation in bronchoalveolar
      lavage fluid relative to that in plasma. In the SDZ (-12 h) plus LPS group, these
      two parameters of acute lung injury were decreased compared with those in the LPS
      alone group. However, they were not decreased in the SDZ (-10 min) plus LPS
      group. We conclude that SDZ attenuates endotoxin-induced acute lung injury when
      it is administered 12 h before LPS injection. The attenuating effects of SDZ are
      speculated to be due to down regulation of the response to endotoxin rather than
      to receptor blocking.

PMID- 8574826
TI  - Cloning of porcine cytokine-specific cDNAs and detection of porcine tumor
      necrosis factor alpha, interleukin 6 (IL-6), and IL-1 beta gene expression by
      reverse transcription PCR and chemiluminescence hybridization.
AB  - A reverse transcription PCR assay with porcine cytokine-specific primers was
      developed to clone cDNA fragments and generate cDNA probes that were specific for
      porcine tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and IL-1
      beta. The specificities of the cDNA PCR products were confirmed by sequence
      analysis on the basis of known porcine cytokine gene sequences. The reverse
      transcription PCR assay was also used to study cytokine mRNA expression in
      lipopolysaccharide (LPS)-stimulated and control unstimulated porcine alveolar
      macrophages. The cDNA products were analyzed in ethidium bromide-stained agarose
      gels, and the transcription level of each cytokine was determined relative to the
      endogenous glyceraldehyde-3-phosphate dehydrogenase (GAPDH) RNA level of each
      cytokine by measuring the intensity of the chemiluminescence hybridization
      signals by densitometric scanning. Various levels of cytokine mRNAs were detected
      in both LPS-stimulated and control unstimulated cells. Thus, TNF-alpha mRNA
      levels were enhanced in the cell cultures stimulated for 6 h with LPS compared
      with those in control cell cultures. No differences in TNF-alpha transcription
      levels between LPS-stimulated and control cells were observed after incubation
      for 24 or 55 h. Enhancements of IL-6 and IL-1 beta mRNA levels were also observed
      in the cultures stimulated with LPS for 6 and 24 h compared with the cytokine
      mRNA levels in control cell cultures. The presence of cytokine mRNA transcripts
      in the LPS-stimulated macrophage cultures correlated with the detection of these
      soluble cytokines by the bioassays. In contrast, no soluble cytokine was detected
      in control macrophage culture supernatants in the presence of cytokine mRNA
      transcripts.

PMID- 8574829
TI  - Comparison of the vibriocidal antibody response in cholera due to Vibrio cholerae
      O139 Bengal with the response in cholera due to Vibrio cholerae O1.
AB  - Vibrio cholerae serogroup O139, now considered to be the second organism capable
      of causing epidemic severe dehydrating cholera, contains a capsular
      polysaccharide which makes it difficult for it to be used in the conventional
      vibriocidal antibody assay optimized for V. cholerae O1. After modification of
      the procedure, which involved the use of specific bacterial strains, a lower
      bacterial inoculum, and increased amounts of complement, the vibriocidal antibody
      responses to V. cholerae O139 were measured in acute- and convalescent-phase sera
      from 33 V. cholerae O139-infected and 18 V. cholerae O1-infected patients and in
      single serum samples from 20 healthy control subjects. The responses in these
      individuals to V. cholerae O1 strains were also determined. Significant
      elevations in the homologous antibody response were found only in the
      convalescent-phase sera from both groups of patients with cholera. These findings
      may explain the basis for the lack of heterologous protection between the two
      serogroups of V. cholerae. Healthy controls had higher background levels of
      vibriocidal antibody to V. cholerae O1 than to V. cholerae O139.

PMID- 8574828
TI  - Detection of human immunodeficiency virus type 1-specific memory cytotoxic T
      lymphocytes in freshly donated and frozen-thawed peripheral blood mononuclear
      cells.
AB  - Loss of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T
      lymphocyte (CTLm) responses is associated with disease progression in HIV-1
      infection. In this study, nonspecific stimulation of peripheral blood mononuclear
      cells (PBMC) from HIV-1-infected homosexual men with anti-CD3 monoclonal antibody
      (MAb) was compared with antigen-specific stimulation with inactivated, autologous
      B lymphoblastoid cells (B-LCL) infected with a vaccinia virus vector encoding HIV
      1 IIIb Gag, Pol, and Env (VV-GPE) for activation of HIV-1-specific CTLm responses
      in a bulk lysis assay and by precursor frequency analysis. The results show that
      VV-GPE-infected B-LCL stimulated on average 10-fold greater anti-HIV-1 CTLm
      activity, as detected in the bulk lysis assay, and 55-fold-greater CTLm precursor
      frequencies specific for the three HIV-1 structural proteins than did stimulation
      with anti-CD3 MAb. This effect was noted with both freshly donated and frozen
      thawed PBMC. The lysis was mediated by CD8+ T cells and was restricted by the
      major histocompatibility class I complex. These data indicate that antigen
      specific stimulation with VV-GPE-infected B-LCL is a highly efficient method for
      detection of anti-HIV-1 CTLm responses that is applicable to noncurrent
      prospective studies with frozen PBMC.

PMID- 8574831
TI  - Intracellular location of Bartonella henselae cocultivated with Vero cells and
      used for an indirect fluorescent-antibody test.
AB  - Bartonella henselae, the major causative agent of cat scratch disease, was
      cocultivated with Vero cells on chamber slides and visualized by indirect
      immunofluorescence by using a patient serum containing specific antibodies.
      Confocal microscopy localized the granular B. henselae-specific fluorescence
      mainly around the nuclei of Vero cells. By transmission electron microscopy,
      these granules were identified as clusters of multiple intracellular organisms.
      Fixed slides with the monolayers of Vero cells with intracellular B. henselae
      were used for an indirect fluorescent-antibody test to investigate the
      seroprevalence of specific immunoglobulin G in 100 serum samples from blood
      donors. Seventy-four serum samples were negative; 19, 3, and 4 were positive at
      dilutions of 1:64, 1:128, and 1:256, respectively. In our population, a serum
      titer of 1:256 or greater should stimulate further investigations. Moreover,
      elucidation of the mechanism by which B. henselae enters the cells may help to
      understand the pathogenesis of cat scratch disease.

PMID- 8574830
TI  - Effect of xanthine derivates and dexamethasone on Streptococcus pneumoniae
      stimulated production of tumor necrosis factor alpha, interleukin-1 beta (IL-1
      beta), and IL-10 by human leukocytes.
AB  - The present study concerns the release of the proinflammatory cytokines
      interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha and of the anti
      inflammatory cytokine IL-10 by human leukocytes in whole blood during stimulation
      with Streptococcus pneumoniae and the effects of various xanthine derivates,
      i.e., pentoxifylline (PTX), caffeine, and theofylline, and of dexamethasone
      (DXM). All three xanthine derivates and DXM inhibited the release of tumor
      necrosis factor alpha, PTX being the most effective. PTX, theofylline, and DXM
      inhibited the release of IL-1 beta, but caffeine did not affect IL-1 beta
      release. The release of IL-10 was significantly reduced by PTX at 24 h and by
      caffeine at 48 h, but DXM increased the release of this cytokine. In sum, the
      results of this study demonstrate that DXM inhibits only the release of
      proinflammatory cytokines but not of the anti-inflammatory cytokine IL-10 by
      human leukocytes, while PTX is the most potent inhibitor of both proinflammatory
      and anti-inflammatory cytokines.

PMID- 8574832
TI  - Characteristics of viral protein expression by Epstein-Barr virus-infected B
      cells in peripheral blood of patients with infectious mononucleosis.
AB  - The frequency of Epstein-Barr virus (EBV) antigen-positive B cells in the
      peripheral blood of patients with infectious mononucleosis compared with that for
      latently EBV-infected individuals was examined by immunocytochemistry. B cells
      positive for Epstein-Barr nuclear antigen (EBNA) 1, EBNA2, and latent membrane
      protein were frequently found in all peripheral B lymphocyte preparations from 25
      patients suffering for 3 to 28 days from infectious mononucleosis by using
      monoclonal antibodies and the alkaline phosphatase anti-alkaline technique. There
      was a significant decrease in the number of positive B cells during the course of
      disease. EBNA1-positive B cells were detected in 0.01 to 2.5% of total B cells
      (median, 0.8%), EBNA2-positive B cells were detected in 0.01 to 4.5% of total B
      cells (median, 0.9%), and latent membrane protein-positive B cells were detected
      in 0.01 to 1.8% of total B cells (median, 0.5%), depending on the duration of
      clinical signs. In contrast, we did not find any EBNA1- or EBNA2-positive B cells
      in 2 x 10(6) peripheral blood B lymphocytes of 10 latently EBV-infected
      individuals, whereas aliquots of the same cell preparations were EBV DNA positive
      by a PCR assay. Therefore, it appears to be possible to detect infectious
      mononucleosis by immunocytochemical determination of latent EBV products, which
      might be of relevance for the diagnosis of EBV reactivations in immunosuppressed
      patients.

PMID- 8574833
TI  - Serum antibody to lipopolysaccharide antigens of Shigella species among U.S.
      military personnel deployed to Saudi Arabia and Kuwait during Operations Desert
      Shield and Desert Storm.
AB  - During Operations Desert Shield and Desert Storm, U.S. troops were at high risk
      of diarrheal disease due to Shigella spp., particularly Shigella sonnei. In order
      to better understand the serologic response to Shigella infection, 830 male U.S.
      combat troops were evaluated before and after the deployment to Saudi Arabia and
      Kuwait for immunoglobulin A (IgA) and IgG anti-Shigella lipopolysaccharide (LPS)
      (antibody to S. sonnei form I and Shigella flexneri serotypes 1a, 2a, and 3a) in
      serum. Just before deployment, 10.3% of the subjects were seropositive for IgA
      and 18.3% were positive for IgG anti-Shigella LPS. IgA and IgG anti-LPS antibody
      levels in serum prior to deployment were significantly associated with nonwhite
      race and ethnicity, birth outside the United States, and antibody to hepatitis A
      virus and Helicobacter pylori. During the deployment, which lasted for a mean of
      131 days, 60% of the subjects reported at least one episode of diarrhea and 15%
      reported an episode of diarrhea with feverishness; also, 5.5% of the subjects
      exhibited IgA seroconversion to Shigella LPS and 14.0% exhibited IgG
      seroconversion. A significant association between the development of diarrheal
      symptoms and either positive predeployment anti-LPS antibody or seroconversion
      was not found. These data indicate that in this population of U.S. Desert Storm
      troops who were at high risk of Shigella infection, there was no apparent
      relation between IgA or IgG anti-Shigella LPS in serum and diarrheal disease.

PMID- 8574834
TI  - Nasopharyngeal antibodies to pneumococcal pneumolysin in children with acute
      otitis media.
AB  - Pneumolysin, an intracellular protein toxin of all clinically relevant
      pneumococcal serotypes, is released in vivo during the autolysis of pneumococci
      and is believed to pave the way for intact pneumococci to invade and cause
      disease. Therefore, antibodies to pneumolysin should prevent its destructive
      function. We measured antibodies to pneumococcal pneumolysin in acute- and
      convalescent-phase nasopharyngeal aspirate samples of 120 children (median age,
      2.5 years) with acute otitis media by enzyme immunoassay. Nasopharyngeal
      immunoglobulin M (IgM) and IgG class antibodies to pneumolysin were rarely
      detectable, whereas IgA class antibody was detected often, occurred independently
      of serum IgA antibody in serum, and correlated with the presence of the secretory
      component in pneumococcal antibody, indicating local production of IgA
      antibodies. Nasopharyngeal IgA antibody to pneumolysin was detected in 93% of the
      children already in the acute phase of otitis. Twenty percent of the children
      developed at least a threefold rise in the pneumolysin-specific IgA antibody
      concentration by the convalescent phase of otitis, with the youngest at 6 months
      of age, regardless of the pneumococcal findings in the nasopharynx or middle ear
      fluid. We suggest that nasopharyngeal IgA antibody to pneumolysin can be produced
      early in life by pneumococcal colonization.

PMID- 8574835
TI  - Recombinant vaccinia viruses expressing hepatitis A virus structural
      polypeptides: detection of an anti-VP0 response in convalescent-phase sera.
AB  - We have generated a number of recombinant vaccinia viruses which expressed the
      hepatitis A virus (HAV) structural polypeptides VP1, VP2, VP3, and VP4, either
      alone or in combination. The relevant sequences encoding these polypeptides were
      amplified from cloned cDNA by PCR and then cloned into the insertion vector
      pGS62. The presence of the HAV structural polypeptide-encoding sequences in the
      recombinant viruses was confirmed by Southern blot analysis, whilst their
      transcription and translation were demonstrated by Northern (RNA) blot analysis
      and immunodetection, respectively. Immunoprecipitation studies using these
      constructs have detected the presence of an anti-VP0 response in human
      convalescent sera following HAV infection. The significance of this finding and
      the usefulness of these constructs in studying cell-mediated immunity during
      recovery from HAV infection are discussed.

PMID- 8574836
TI  - Dysregulated production of interleukin-10 (IL-10) and IL-12 by peripheral blood
      lymphocytes from human immunodeficiency virus-infected individuals is associated
      with altered proliferative responses to recall antigens.
AB  - The loss of immune function following infection with human immunodeficiency virus
      (HIV) may result from altered production of immunoregulatory cytokines such as
      interleukin-10 (IL-10) and IL-12. In this study, we analyzed IL-10 and IL-12
      production by mitogen-stimulated peripheral blood mononuclear cells (PBMC) from
      HIV+ individuals and correlated their levels with proliferative responses to the
      recall antigens HIV p25 and influenza virus. We report two distinct groups of
      HIV+ patients. One group produced small amounts of IL-10, had PBMC that
      proliferated in response to recall antigens, and demonstrated enhanced recall
      antigen-induced proliferation upon addition of anti-IL-10 antibodies and/or IL
      12. Conversely, the second group produced high levels of IL-10, had PBMC that
      failed to proliferate to recall antigens, and did not demonstrate enhanced
      proliferation upon addition of anti-IL-10 antibodies and/or IL-12. Mitogen
      stimulated PBMC from both groups produced significantly lower levels of IL-12
      than did those from HIV- controls. Analysis of the source of the IL-10-producing
      cell subset in PBMC demonstrated that in HIV+ individuals, IL-10 is produced by
      monocytes, while in HIV- controls, it is produced by both T cells and monocytes.
      Taken together, our results suggest that monocytes from HIV+ individuals secrete
      decreased amounts of IL-12, a Th1-type cytokine, which may lead to the
      development of Th2-type responses characterized by high IL-10 secretion and
      immune dysfunction.

PMID- 8574837
TI  - Characterization of preparations enriched for Streptococcus mutans fimbriae:
      salivary immunoglobulin A antibodies in caries-free and caries-active subjects.
AB  - The ability of bacteria to adhere to salivary pellicle-coated enamel tooth
      surfaces is a critical step in oral bacterial colonization. Oral bacteria adhere
      to receptors of host origin in salivary pellicle. Streptococcus mutans has been
      identified as the major etiological agent of human dental caries and composes a
      significant proportion of the oral streptococci in carious lesions. Bacterial
      fimbriae are small (100 to 300 nm) hairlike appendages emanating from the cell
      surface. Preparations enriched for S. mutans fimbriae were isolated by a shearing
      technique and alternating high- and low-speed centrifugations. A representative
      fimbrial preparation had two distinct double bands comprising four proteins of
      approximately 100 to 200 kDa and one faint band at 40 kDa on reducing sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis/immunoblots and had
      demonstrable glucosyltransferase activity. Rabbit antisera raised against the
      preparation specifically stained the fuzzy coat of S. mutans, demonstrating short
      fimbria-like structures protruding 100 to 200 nm from the cell surface. Controls
      without antifimbria antibody did not exhibit this staining. There were
      significantly higher (P < or = 0.05) levels of salivary immunoglobulin A, but not
      serum immunoglobulin G, antibodies to the enriched S. mutans fimbria preparation
      by enzyme-linked immunosorbent assay from caries-free subjects than from caries
      active subjects. The results suggest that S. mutans fimbriae may be an important
      adherence factor to which caries-free subjects mount a protective salivary immune
      response.

PMID- 8574838
TI  - Selective increases in antibody isotypes and immunoglobulin G subclass responses
      to secreted antigens in tuberculosis patients and healthy household contacts of
      the patients.
AB  - Mycobacterium tuberculosis-specific antibodies (immunoglobulin M [IgM], IgE, IgG,
      and IgG subclasses) were determined in 164 tuberculosis patients (pulmonary
      involvement, n = 135; lymph node involvement, n = 29), 59 healthy household
      contacts (HC), and 51 healthy endemic donors (EC) by a quantitative enzyme-linked
      immunosorbent assay for reactivity with culture filtrate. Among the isotypes,
      significant differences between tuberculosis patient groups with either pulmonary
      or lymph node involvement and healthy control groups (HC and EC) were detected
      only for IgG (P < 0.001) and IgG1 (P < 0.001) antibodies. Pulmonary patients also
      showed a significant difference with IgM (P < 0.01) and IgE (P < 0.05)
      antibodies. HC showed elevation of only IgM antibodies compared with EC,
      indicating that IgM antibodies may be an indicator of recent infection with M.
      tuberculosis. These results suggest that the switching of IgM antibody response
      to IgG1 is a critical event in disease progression. Polyclonal IgG1, IgG3, and
      IgE antibodies also showed significant elevation (P < 0.05) in patients compared
      with EC. A strong correlation (rho = 0.254; P < 0.003) was observed between M.
      tuberculosis-specific IgG1 and polyclonal IgG1 in patients, suggesting that
      activations of antigen-specific and polyclonal antibodies are related events. No
      correlation was found between IgG1 antibodies and purified protein derivative
      skin test results. Since IgG1 antibody responses to culture filtrate are present
      only after disease establishment, IgG1 responses could provide a useful
      diagnostic marker of disease.

PMID- 8574839
TI  - Molecular analysis of highly enriched populations of T-cell-depleted monocytes.
AB  - CD4+ T lymphocytes and monocytes/macrophages are important components of the
      immune system. Blood monocytes are usually targeted for studies of the human
      macrophage lineage cells because of their accessibility through blood sampling.
      Most separation techniques currently available to obtain human monocytes either
      require large volumes of blood or do not yield a monocyte fraction sufficiently
      depleted of other cell types. We have developed a simple strategy to isolate a
      highly enriched population of monocytes from small volumes (< 6 ml) of peripheral
      blood by using an anti-CD14 monoclonal antibody and magnetic microspheres. Yields
      of monocytes ranged from 75 to 80% of CD14+ cells in peripheral blood. CD4+ T
      cells were subsequently selected from the monocyte-depleted peripheral blood by
      using an anti-CD4 monoclonal antibody and immunomagnetic beads. The effectiveness
      of immunomagnetic selection to yield a monocyte population highly depleted of T
      cells was analyzed by using a sensitive molecular strategy based on PCR
      amplification and detection of T-cell receptor (TCR) gene rearrangements. The
      relative frequency of rearranged TCRs within the monocyte population was compared
      with the frequency of rearranged TCRs within the CD4+ T-cell fraction from the
      same individual. Molecular analysis indicated that a viable monocyte population
      which contains fewer than 2% residual T lymphocytes can be consistently selected
      from small aliquots of blood.

PMID- 8574840
TI  - Expression of recombinant feline tumor necrosis factor is toxic to Escherichia
      coli.
AB  - The tumor necrosis factor (TNF) genes from cats, horses, and pigs have all been
      cloned into the pFLAG-1 fusion protein expression vector (International
      Biotechnologies, Inc., Kodak, New Haven, Conn.). Growth curves for Escherichia
      coli containing the pFLAG-1 vector alone and the pFLAG-1 vector containing the
      TNF gene from each species were determined by visible light spectrophotometry (at
      600 nm). Porcine TNF, equine TNF, and feline TNF cultures had slower doubling
      rates than cultures containing the pFLAG-1 vector alone. Cultures of cells
      transformed with feline TNF reached peak densities at 3 to 4 h and then decreased
      to near initial densities prior to the recovery of growth. The induction of
      expression with isopropyl-beta-D-thiogalactopyranoside (IPTG) arrested the growth
      of fresh feline TNF cultures for 6 h, which was followed by complete recovery.
      This inhibition occurred in two strains of E. coli (LL308 and JM101). Induced
      feline TNF cultures expressed the TNF-FLAG fusion protein for the first 6.5 h.
      Uninduced cultures expressed low levels of fusion protein. The feline TNF-pFLAG-1
      vector was purified from cells expressing fusion protein and from cells with
      recovered growth curves. Sequencing the vector demonstrated the complete feline
      TNF gene and tac promoter in cells expressing the fusion protein and a deletional
      mutation of the tac promoter site in recovered cells. In contrast to equine and
      porcine TNF, the expression of recombinant feline TNF is toxic to E. coli.
      Alterations in protein folding and the prevention of secretion of the feline
      protein may explain the toxic effect.

PMID- 8574841
TI  - Identification of outer membrane proteins as target antigens of Pseudomonas
      aeruginosa Homma serotype M.
AB  - Pseudomonas aeruginosa is routinely serotyped in Japan by using the Homma scheme.
      The serotypes (O serotypes) are based on the chemical structure of the O
      polysaccharide portion of the lipopolysaccharide (LPS). However, the nature of
      the Homma serotype M antigen has remained obscure because strains classified as
      serotype M usually have the rough phenotype. I characterized the target antigen
      of serotype M. The results of Western blotting (immunoblotting) showed that
      commercially available typing monoclonal antibody (MAb) against serotype M
      specifically bound to outer membrane protein (Opr) G and that typing rabbit
      antiserum specific for serotype M mainly contained antibodies against Oprs F and
      H2. These Oprs were distributed among all P. aeruginosa strains tested, including
      the serotype standard, serotype M and nontypeable strains, and a series of LPS
      core-defective mutants derived from strain PAC1. However, the rough mutants
      derived from strain PAC1 agglutinated with the anti-serotype M antibodies,
      whereas the smooth strains did not. LPS preparations from serotype M strains
      possessed few or no polysaccharide chains. These strains had higher levels of
      binding activity with anti-serotype M MAb, as well as with anti-lipid A MAb,
      which specifically bound to the cell surface of the rough-natured gram-negative
      bacterial strains with high activity. The anti-serotype M antiserum also
      contained rough-LPS-specific antibodies, but the epitope was distributed among
      only a few strains. The results suggested that the Oprs acted as the serotype M
      antigen and that LPS did not. In conclusion, the rough strains agglutinated with
      anti-Opr antibodies and were distinguished as serotype M from the smooth strains
      of other serotypes, because the antibodies were accessible to the cell surface
      lacking O polysaccharides. I supposed that Homma serotype M is an index of the
      rough nature of P. aeruginosa strains rather than one of the O serotypes.

PMID- 8574842
TI  - Quantitative analysis of phagocytosis and killing of Cryptococcus neoformans by
      human peripheral blood mononuclear cells by flow cytometry.
AB  - Monocytes may represent an important defense mechanism in disseminated
      cryptococcosis. We have developed a flow cytometric method to study the
      interaction of Cryptococcus neoformans with monocytes. For phagocytosis, C.
      neoformans was labelled with fluorescein isothiocynate (FITC). Monocytes were
      identified on the flow cytometer by labelling with anti-CD14-R-phycoerythrin.
      Discrimination between attached cells (association) and internalized cells
      (uptake) was made by quenching FITC-labelled C. neoformans with trypan blue. Only
      internalized cells kept their FITC fluorescence after quenching. For comparison
      under the microscope, specific staining of the cell wall of C. neoformans with
      Uvitex was used. Internalized C. neoformans cells were not stained, as Uvitex was
      occluded from phagocytes. To assay killing, C. neoformans was labelled with 0.2
      mM 2'-7(1)-bis(2-carboxyethyl)-5-carboxyfluorescein acetoxymethylester. After
      phagocytosis of labelled cells by monocytes, blood cells were lysed with 25 mM
      deoxycholate. Viable yeast cells retained the fluorescence, but nonviable cells
      lost it. Quantitative counts of viable cells on Sabouraud dextrose agar were
      performed for comparison. The change in the relative fluorescence of green within
      the monocyte region was used to quantitate association, uptake, and killing of C.
      neoformans by monocytes on the flow cytometer. The flow cytometry methods showed
      that 18% +/- 2%, 35% +/- 14%, 50% +/- 11%, 51% +/- 6% of monocytes had become
      associated with C. neoformans after 0, 30, 60, and 120 min, respectively. After 2
      h of phagocytosis time, 30% of C. neoformans-associated monocytes had taken up
      the cells, and killing rates of 23% +/- 17%, 22% +/- 9%, and 40% +/- 13% were
      obtained with effector-to-target cell ratios of 1:1, 10:1, and 50:1,
      respectively. Results with the flow cytometry methods compared favorably with
      those by the conventional methods used, but the flow cytometry methods are
      simpler, rapid, more reproducible, and objective.

PMID- 8574843
TI  - A family cluster of an immune escape variant of hepatitis B virus infecting a
      mother and her two fully immunized children.
AB  - A hepatitis B virus (HBV) immune escape variant which results from a substitution
      of glycine by arginine at position 145 (arginine-145) in the immunodominant
      neutralization epitope of the S protein was found to infect one child in a
      seroepidemiologic survey of 1,812 vaccinated children. The child's mother and a
      younger brother were also infected by the same HBV variant, despite a greater
      than accepted level of protective antibody (anti-HBV surface antigen) in both the
      index child (30 mIU/ml) and the brother (> 20,000 mIU/ml). Our findings suggest
      the perinatal or horizontal transmission of the arginine-145 HBV variant from
      mother to child, but the ability of this variant to propagate among the
      vaccinated children remains unknown.

PMID- 8574844
TI  - Correlation of lactoferrin with neutrophilic inflammation in body fluids.
AB  - We have reported that lactoferrin, a 77-kDa iron-binding glycoprotein found in
      secondary neutrophil granules, provides a useful marker of fecal leukocytes in
      fecal specimens from patients with inflammatory diarrhea (R. L. Guerrant, V.
      Araujo, E. Soares, K. Kotloff, A. A. M. Lima, W. H. Cooper, and A. G. Lee, J.
      Clin. Microbiol. 30:1238-1242, 1992). In order to determine the usefulness of
      this marker of neutrophilic inflammation in different body fluids, we examined
      blood, gingival swabs, sputum, and saliva using antilactoferrin antibodies
      (lactoferrin latex agglutination [LFLA]). LFLA titers in whole blood samples were
      < or = 1:4 in all eight samples from patients with neutropenia (absolute
      neutrophil count [ANC] = < 150 polymorphonuclear cells [PMNs] per microliter), <
      or = 1:8 in samples from 13 individuals with moderate leukocyte counts (ANC = 150
      to 8,000), and 1:8 to 1:32 in samples from six patients with neutrophilia (ANC >
      8,000). While the overlap precludes a useful role in the identification of
      neutropenia, these data confirm that lactoferrin titers of > 1:100 indeed
      indicate inflammation in fluid specimens. On quantitative elution of lactoferrin
      from gingival swabs, all 7 patients with dental plaque had titers of 1:200 to
      1:400; 9 of 12 patients with clinical gingivitis had LFLA titers of 1:200 to
      1:1,600, while all 7 individuals with healthy gums and teeth and 4 edentulous
      patients had LFLA titers of < or = 1:100. Eight purulent sputum samples had
      titers of > or = 1:400 (7 were 1:1,600) while 11 normal saliva samples showed
      titers of < or = 1:100. Lactoferrin titers in sputum, gingival swabs, and whole
      blood correlate with the presence of neutrophils or inflammation in these
      specimens and may offer a convenient rapid test for inflammatory processes.

PMID- 8574845
TI  - Alterations in peripheral blood mononuclear cell cytokine production in response
      to phytohemagglutinin in multiple sclerosis patients.
AB  - Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central
      nervous system (CNS). The disease is characterized by inflammatory lesions in the
      white matter of the CNS, consisting of a specific immune response to the myelin
      sheath. We investigated peripheral blood mononuclear cell (PBMC) cytokine
      production by enzyme-linked immunosorbent assays of 21 MS patients and 19 age
      matched normal controls in response to the T-cell mitogen phytohemagglutinin
      (PHA). Peripheral blood mononuclear cells were cultured in medium alone or in
      medium with 5 micrograms of PHA per ml for 48 h, and culture supernatants were
      collected for analysis. Cytokines selected for study were interleukin-10 (IL-10),
      gamma interferon (IFN-gamma), IL-2, and IL-4. All cytokine activities described
      were expressed as concentrations per 500,000 cells. We found that 48% (10 of 21)
      of the MS patients produced small but detectable levels of IL-10 in medium alone,
      compared with 26% (5 of 18) of the controls. We found that the MS patients
      produced significantly higher quantities of IL-10 protein than the controls in
      response to PHA (mean supernatant concentrations of IL-10 for patients and
      controls, 421 and 204 pg/ml, respectively [P < 0.05]). No significant differences
      were detected in the production of IL-2, IFN-gamma, and IL-4 between patients and
      controls in response to PHA, although patients appeared to display a trend toward
      decreased production of IFN-gamma.

PMID- 8574846
TI  - Comparison of PCR-generated fragments of the mce gene from Mycobacterium
      tuberculosis, M. avium, M. intracellulare, and M. scrofulaceum.
AB  - Nineteen strains representing 13 species of mycobacteria were tested for the
      ability to serve as PCR templates for the production of a 293-bp fragment of the
      mycobacterial mce gene. The mce gene is a virulence factor recently sequenced
      from Mycobacterium tuberculosis. PCR products were obtained for only the species
      of the Mycobacterium tuberculosis complex (MTC) and the Mycobacterium avium-M.
      intracellulare-M. scrofulaceum complex. The fragment was sequenced from M.
      tuberculosis (one strain), M. avium (three strains), M. intracellulare (two
      strains), and M. scrofulaceum (two strains). Sequence comparisons suggest that
      the fragments from each of the species are regions that code for a similar
      product. One of the M. scrofulaceum strains yielded a sequence whose most
      probable reading frame was truncated by an amber stop codon caused by a single
      nuclei acid difference from the other sequences. The amino acid sequences from
      the non-MTC sequences cluster together, displaying fewer differences from each
      other than from the M. tuberculosis sequence and the truncated M. scrofulaceum
      sequence. Principal component analysis of the distance matrix displays the
      clustering of the M. avium and M. intracellulare sequences into single-species
      clusters. It is concluded that at least one open reading frame of the mce gene is
      found, although it is discernibly different, in pathogenic mycobacteria other
      than the MTC.

PMID- 8574847
TI  - Mouse Eotaxin expression parallels eosinophil accumulation during lung allergic
      inflammation but it is not restricted to a Th2-type response.
AB  - A model of lung eosinophilia based on the repeated exposure of mice to
      aerosolized OVA has been used to identify C-C chemokine genes expressed at stages
      of massive eosinophil infiltration. We describe the identification and cloning of
      a cDNA that encodes a mouse C-C chemokine with 68% amino acid identity to guinea
      pig Eotaxin. The recombinant protein encoded by this gene displays potent and
      specific chemotactic activity for eosinophils, both in vivo and in vitro. Its
      mRNA levels parallel the kinetics of eosinophil accumulation in the lung during
      the experimentally induced eosinophilia and it is mainly produced by type I
      alveolar epithelial cells. The mRNA expression of mouse Eotaxin is not restricted
      to Th2 T cells in vitro and is independent of the development of a Th2-type
      response during N. brasiliensis infection, in vivo.

PMID- 8574848
TI  - IL-5-deficient mice have a developmental defect in CD5+ B-1 cells and lack
      eosinophilia but have normal antibody and cytotoxic T cell responses.
AB  - Mice deficient in interleukin-5 (IL-5-/- mice) were generated by gene targeting
      in embryonal stem cells. Contrary to previous studies, no obligatory role for IL
      5 was demonstrated in the regulation of conventional B (B-2) cells, in normal T
      cell-dependent antibody responses or in cytotoxic T cell development. However,
      CD5+ B cells (B-1 cells) in the peritoneal cavity were reduced by 50%-80% in 2
      week-old IL-5-/- mice, returning to normal by 6-8 weeks of age. The IL-5-/- mice
      did not develop blood and tissue eosinophilia when infected with the helminth
      Mesocestoides corti, but basal levels of eosinophils with normal morphology were
      produced in the absence of IL-5. IL-5 deficiency did not affect the worm burden
      of infected mice, indicating that increased eosinophils do not play a significant
      role in the host defence in this parasite model.

PMID- 8574849
TI  - Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes.
AB  - It is widely believed that viral clearance is mediated principally by the
      destruction of infected cells by CTLs. In this report, we use a transgenic mouse
      model of HBV replication to demonstrate that this assumption may not be true for
      all viruses. We find that adoptively transferred virus-specific CTLs can abolish
      HBV gene expression and replication in the liver without killing the hepatocytes.
      This antiviral function is mediated by IFN gamma and TNF alpha secreted by the
      CTL or by the antigen-nonspecific macrophages and T cells that they activate
      following antigen recognition. These cytokines activate two independent virocidal
      pathways: the first pathway eliminates HBV nucleocapsid particles and their cargo
      of replicating viral genomes, while the second pathway destabilizes the viral
      RNA. Intracellular viral inactivation mechanisms such as these could greatly
      amplify the protective effects of the immune response, while failure of such
      mechanisms could lead to viral persistence or to the death of the host.

PMID- 8574850
TI  - T cell receptor delta gene rearrangement and T early alpha (TEA) expression in
      immature alpha beta lineage thymocytes: implications for alpha beta/gamma delta
      lineage commitment.
AB  - Mature T cells comprise two mutually exclusive lineages expressing heterodimeric
      alpha beta or gamma delta antigen receptors. During development, beta, gamma, and
      delta genes rearrange before alpha, and mature gamma delta cells arise in the
      thymus prior to alpha beta cells. The mechanism underlying commitment of immature
      T cells to the alpha beta or gamma delta lineage is controversial. Since the
      delta locus is located within the alpha locus, rearrangement of alpha genes leads
      to deletion of delta. We have examined the rearrangement status of the delta
      locus immediately prior to alpha rearrangement. We find that many thymic
      precursors of alpha beta cells undergo VDJ delta rearrangements. Furthermore, the
      same cells frequently coexpress sterile T early alpha (TEA) transcripts
      originating 3' of C delta and 5' of the most upstream J alpha, thus implying that
      individual alpha beta lineage cells undergo sequential VDJ delta and VJ alpha
      rearrangements. Finally, VDJ delta rearrangements in immature alpha beta cells
      appear to be random, supporting models in which alpha beta lineage commitment is
      determined independently of the rearrangement status at the TCR delta locus.

PMID- 8574851
TI  - Single-cell PCR analysis of TCR repertoires selected by antigen in vivo: a high
      magnitude CD8 response is comprised of very few clones.
AB  - Taking advantage of a potent MHC class I-restricted response that allows the
      identification of antigen-selected CD8 T cells directly ex vivo, we characterized
      the antigen-specific T cell repertoires that develop in individual mice by single
      cell PCR analysis. Each of the immune mice displayed distinct yet structurally
      similar TCR repertoires. The overall repertoire size was estimated to be in the
      range of 15-20 for most mice. No major differences were observed between primary
      and secondary responses. Moreover, for a hyperimmunized mouse the antigen
      specific TCR repertoire expressed 8 months after the initial immunization was
      very similar to that found at the peak of the primary response. Our results
      demonstrate that a high magnitude immune response may be composed of very few
      clones, and that at least in the system analyzed, the memory response largely
      reflects the repertoire selected by the peak of the primary response.

PMID- 8574852
TI  - Somatic hypermutation of immunoglobulin genes is linked to transcription
      initiation.
AB  - To identify DNA sequences that target the somatic hypermutation process, the
      immunoglobulin gene promoter located upstream of the variable (V) region was
      duplicated upstream of the constant (C) region of a kappa transgene. Normally,
      kappa genes are somatically mutated only in the VJ region, but not in the C
      region. In B cell hybridomas from mice with this kappa transgene (P5'C), both the
      VJ region and the C region, but not the region between them, were mutated at
      similar frequencies, suggesting that the mutation mechanism is related to
      transcription. The downstream promoter was not occluded by transcripts from the
      upstream promoter. In fact, the levels of transcripts originating from the two
      promoters were similar, supporting a mutation model based on initiation of
      transcripts. Several "hot-spots" of somatic mutation were noted, further
      demonstrating that this transgene has the hallmarks of somatic mutation of
      endogenous immunoglobulin genes. A model linking somatic mutation to
      transcription-coupled DNA repair is proposed.

PMID- 8574853
TI  - The role of Ly49A and 5E6(Ly49C) molecules in hybrid resistance mediated by
      murine natural killer cells against normal T cell blasts.
AB  - We address the mechanism of hybrid resistance (HR) in vitro using NK effector
      cells and target lymphoblasts from H-2b, H-2d, and H-2b/d mice. The 5E6 (Ly49C)+
      subset of F1 NK cells lyse BALB/c (H-2d) but not B6 (H-2b) targets unless either
      anti-5E6 or anti-H-2Kb MAbs are present. H-2Dd transgenic B6 (D8) targets are not
      susceptible to F1 Ly49A+ effectors. Furthermore, 5E6+ Ly49A+ F1 effectors lyse B6
      and BALB/c targets only in the presence of anti-5E6 and anti-Ly49A MAbs,
      respectively. Thus, recognition of H-2Kb by 5E6 and H-2Dd by Ly49A transduce
      independent inhibitory signals. Moreover, anti-5E6 MAbs enable 5E6+ BALB/c NK
      cells to lyse (BALB/c x B6)F1 targets. These data support the "missing self" and
      not the "hemopoietic histocompatibility antigen" hypothesis for HR. In addition,
      5E6+ NK cells from BALB/c and BALB.B, but not B6 or (BALB/c x B6)F1, mice receive
      negative signals from both H-2d and Kb class I antigens. Thus, allelic
      differences in 5E6 (C57BL versus BALB) may regulate recognition events by NK
      cells.

PMID- 8574855
TI  - Association between HLA-DM and HLA-DR in vivo.
AB  - The exchange of HLA class II-associated invariant chain peptides (CLIP) for
      cognate peptide is catalyzed by HLA-DM under acidic conditions in vitro by an
      unknown mechanism. Here, we show an association between HLA-DM and HLA-DR in vivo
      by coprecipitation of the two heterodimers. The association is favored at low pH
      and in the nonionic detergent digitonin. Most DM-DR complexes are isolated from
      dense subcellular fractions. Recovery of HLA-DM by the conformation-dependent DR3
      monoclonal antibody 16.23 suggests an association with HLA-DR heterodimers beyond
      the stage at which CLIP is released. The additional N-linked glycan on mutant DR3
      molecules isolated from the 10.24.6 cell line, which interferes with DM-enhanced
      CLIP release from DR3 in vitro, also affects the DM-DR interaction.

PMID- 8574854
TI  - Recruitment of tyrosine phosphatase HCP by the killer cell inhibitor receptor.
AB  - Cytolysis of target cells by natural killer (NK) cells and by some cytotoxic T
      cells occurs unless prevented by inhibitory receptors that recognize MHC class I
      on target cells. Human NK cells express a p58 inhibitory receptor specific for
      HLA-C. We report association of the tyrosine phosphatase HCP with the p58
      receptor in NK cells. HCP association was dependent on tyrosine phosphorylation
      of p58. Phosphotyrosyl peptides corresponding to the p58 tail bound and activated
      HCP in vitro. Furthermore, introduction of an inactive mutant HCP into an NK cell
      line prevented the p58-mediated inhibition of target cell lysis. These data imply
      that the inhibitory function of p58 is dependent on its tyrosine phosphorylation
      and on recruitment and activation of HCP.

PMID- 8574856
TI  - Circulation of hematopoietic progenitors in the mouse embryo.
AB  - We used a sensitive in vitro culture system to follow, in embryonic blood, the
      number and state of commitment of B cell precursors along ontogeny. We describe a
      wave of circulating multipotent progenitors, first detectable at day 10 of
      gestation, and reaching a maximum in absolute numbers at day 12. They are
      undetectable by day 14 of gestation, when committed B cell precursors can be
      detected in fetal liver. Embryonic marrow contains B cell progenitors by day 15.
      We propose that fetal liver, thymus, and bone marrow are colonized by the same
      wave of multipotent hematopoietic cells and define embryonic blood at day 11 of
      gestation as an important source of multipotent hematopoietic cells, virtually
      deprived of committed and mature contaminants.

PMID- 8574857
TI  - Effect of supplementation of milk fat with peanut oil on blood lipids and
      lipoproteins in infants.
AB  - Three different groups of infants were fed with different formulae based on milk
      fat. Group I received cow's milk fat formulae with 20% butter fat whereas groups
      II and III received a formulae which was supplemented with 50 and 33% of peanut
      oil supplementation in 20% milk fat respectively. Anthropometric measurements,
      cholesterol, triglyceride, lipoproteins and plasma fatty acids were followed up
      to a period of 6 months. The results indicated that cow's milk-fed infants had
      higher cholesterol levels (P < 0.01) than the other two groups. No significant
      differences with respect to high-density lipoproteins (HDLs) were found, whereas
      low-density lipoproteins (LDLs) and very low-density lipoproteins (VLDls (VLDls)
      were found to be increasing up to a period of 6 months. No significant
      differences were observed with respect to saturated fatty acids and oleic acid
      (18:1) levels whereas linoleic acid (18:2) clearly showed a proportional
      relationship between the intake and plasma levels, indicating a positive
      correlation. Arachidonic acid (20:4) did not, however, show a proprotionate
      relationship with respect to linoleic acid (18:2) intake. The triene/tetraene,
      oleic/linoleic, linoleic/arachidonic and total n6 fatty acids were all normal
      indicating normal activity of desaturase and elongase enzymes for the optimal
      utilisation of linoleic acid. Thus, the present study suggests that a vegetable
      oil such as peanut oil could be used in milk fat to improve the essential fatty
      acid (EFA) status of infants.

PMID- 8574858
TI  - Irradiated versus fumigated spices in sausage.
AB  - The efficacy of gamma radiation and ethylene oxide fumigation as decontaminating
      treatments for spices used in sausages was compared. Microbial loads of sausages
      containing irradiated, fumigated or non-treated spices were examined over three
      intervals of time. No significant differences between microbial loads of Mexican
      sausages containing irradiated spices (10 kGy) verses ethylene oxide-treated
      spices were found. Mexican sausages containing treated spices had significantly
      lower yeast, mould and spore counts than control sausages. After 8 weeks of
      storage, only the microbial loads of control sausages suggested spoilage. No
      discernable differences in treatment efficacy were noted with respect to yeast,
      mould and spore counts in Italian sausages.

PMID- 8574859
TI  - Satiety effects of spinach in mixed meals: comparison with other vegetables.
AB  - The effects of vegetables in mixed meals on satiety were evaluated by varying the
      dose (portions 150 and 250 g containing 4.3 and 7.2 g of dietary fibre,
      respectively) and structure (cut and minced) of microwaved spinach. A control
      meal without spinach and the test meals with spinach were balanced regarding
      energy (2000 kJ) and digestible carbohydrates (59 g, 51 E%) and with protein and
      fat as far as possible similar. The meals were served in the morning, after an
      overnight fast, to ten healthy male volunteers. Satiety was registered and blood
      glucose as well as plasma insulin and C-peptide were analysed at regular
      intervals until 3.5 h postprandially. The largest spinach portions augmented
      satiety and reduced the postprandial glucose response. The total satiety scores
      seemed to be correlated positively to both the dietary fibre and the water
      content in the vegetable. Differences in structure had no influence on satiety
      scores.

PMID- 8574860
TI  - A quantitative model for prediction of iron bioavailability from Indian meals: an
      experimental study.
AB  - The major goal of the study was to explore the possibility of developing an
      updated model that integrates the effect of various enhancers and inhibitors for
      predicting the potential availability of iron from typical Indian vegetarian
      meals. The interaction effects of four constituents namely ascorbic acid, citric
      acid, tannic acid and calcium phosphate was studied using a standard cereal meal
      (STD meal) providing 3 mg non-heme iron/250 ml homogenate. Based on the data, a
      regression equation was evolved which was tested for its predictive power as
      applied to a set of 10 typical Indian meals. Regression analysis of the data
      revealed that both ascorbate and citrate emerged as equally strong enhancers
      while tannate and calcium phosphate demonstrated strong inhibitory effect on iron
      availability in the STD meal. Further, when the prediction equation, generated on
      the basis of the interaction effect data was applied to the typical Indian meals,
      it showed a high correlation coefficient (r = 0.76) between the analysed values
      for iron availability vs the values computed using the enhancer and inhibitor
      contents of the meals. Comparison with the only other model available in the
      literature namely that of Monsen & Balintfy (1982) revealed that the present
      model was far better in predicting iron availability from cereal based Indian
      meals (r = 0.76) than Monsen's model (r = 0.19). The findings of the present
      study substantiated the hypothesis that a regression model, evolved from a cereal
      meal, by integrating the effect of enhancers as well as inhibitors, rather than
      only enhancers, provides a more precise estimate of iron availability from
      typical Indian meals. A limitation of the model however, was that phytate could
      not be incorporated into the equation.

PMID- 8574861
TI  - Selenium content of convenience and fast foods in Ayrshire, Scotland.
AB  - Selenium concentrations were determined via hydride generation atomic absorption
      spectrometry in more than 100 convenience and fast foods including 34 vegetarian
      dishes. The foods were purchased mainly in Ayrshire, Scotland but some came from
      other parts of the UK. The results indicate a considerable amount of selenium in
      certain mushrooms, spinach, fish, offals and chicken-based products. The selenium
      content of beef- and pork-based products was generally somewhat lower.
      Vegetarians having a sufficient intake of mushrooms (in particular button and
      closed cap mushrooms) and spinach do not seem to be at risk of selenium
      deficiency provided of course that the selenium in mushrooms, in particular, is
      bioavailable.

PMID- 8574862
TI  - Feeding of lactic acid-fermented high nutrient density weaning formula in
      paediatric settings in Ghana and Nigeria: acceptance by mother and infant and
      performance during recovery from acute diarrhoea.
AB  - A period of acute diarrhoea in infants is often associated with anorexia and
      weight loss. Catch-up growth is, therefore, necessary and this depends very much
      on the type of food, in terms of nutrient density, protein quality and
      digestibility, given to the child. Fermented (F) and non-fermented (NF) maize
      soybean porridges of increased nutrient density were formulated and compared with
      traditionally fermented maize-only porridge (P) for acceptability using mothers
      in peri-urban Ghana as well as urban Nigeria as subjects. Subsequently, infants
      hospitalised in paediatric wards for acute diarrhoea, from the same communities
      in both countries, were assigned randomly to one or other of the three porridges.
      Infant subjects in all cases fell within the ages of 6-15 months. Complementary
      to regular breast-feeding, infants could consume as much porridge as they wanted
      and their total daily consumption was interpreted as an indication of acceptance.
      Although mothers in both the environments of Ghana and Nigeria rated P as more
      acceptable than F and NF, no significant difference was recorded in the
      quantitative intake by infants of the three formula groups. By adding enzyme-rich
      cereal malt flour (at the 1-5% level by weight) as a viscosity-thinning agent to
      F and NF porridges, it was possible to feed these porridges to infants at total
      solids concentration levels of 20-25% (wet basis) which is approximately double
      the solid matter content of the P porridge. Consequently, the daily nutrient
      intake by infants consuming F and NF porridges was considerably higher compared
      to the P porridge group. It is concluded that the concept of high nutrient
      density weaning foods is a feasible vehicle for an improvement of nutrient supply
      to infants.

PMID- 8574863
TI  - Effect of deep-fat frying on fat oxidation in soybean oil.
AB  - The frying performance and stability of pure soybean oil (PSBO), soybean oil
      blended with palm kernel olein and PSBO with an antioxidant mixture of butylated
      hydroxytoluene (BHT), butylated hydroxyanisole (BHA), propyl gallate and citric
      acid were compared. The oils were subjected to intermittent frying (up to 15
      fryings, without any 'topping up') of potato slices, at 180 degrees C for a
      period of and 337 min. Analytical determinations on the oils included the
      peroxide value (PV), iodine value (IV), free fatty acid (FFA) value,
      saponification value (SV) and the refractive index (RI). Changes in the product
      at the sensory level were also assessed. Results showed that (1) fat oxidation
      hence, reduction of unsaturated fatty acids, as indicated by changes in the IV,
      was non-significant in the treated oils, (2) hydrolysis of fats, as shown by
      changes in the FFA value from the first to last frying, was lowest in the blended
      oil but highest in PSBO, (3) the same trend as above was observed for PV, an
      indicator of fat oxidation and rancidity, (4) changes in SV were non-significant
      in the treated soya oils while PSBO with the antioxidant showed the least change
      in RI, (5) treated oils exhibited no visual increase in viscosity or turbidity
      and (6) PSBO with the antioxidant had the lightest colour at the end of the
      frying period. Taste panellists were unable to discriminate between products
      fried in the treated oils and in PSBO. Sensory assessment showed an improved
      quality of the chips fried in the blend. Chips fried in PSBO scored the lowest
      ratings. Thus, the overall results showed an improved behaviour and quality of
      the treated oils in terms of themal stability during frying.

PMID- 8574864
TI  - Is breast cancer avoidable? Could dietary changes help?
AB  - In the US, the life time odds of developing breast cancer has reached one in
      eight, with an incidence rate of 85 per 100,000 world population. The rate is
      half or less in women in some Mediterranean countries. At the extreme are rural
      African women whose rate is approximately 5-10 per 100,000. In African, compared
      with White women, protective factors include (1) reproductive behaviour, namely,
      slower growth before and after puberty, later age at menarche, high teenage
      pregnancy, high parity and long periods of lactation and amenorrhoea and (2) a
      diet of relatively low energy intake and of low-fat and high-fibre contents. In
      the Mediterranean setting, major dietary protective factors include a relatively
      low intake of saturated fat and high intakes of monounsaturated fat and of
      vegetables and fruit. Among White women, a reversion to protective reproductive
      behaviour is out of the question. Only in respect of diet, could significant
      avoiding action be taken. Adoption of an African type diet is wholly
      impracticable. Moreover, even conformation to a former Mediterranean diet, which
      is already changing, would be difficult, requiring reorientation of fat
      composition and large rises in intakes of vegetable and fruit. However, with
      resolution, were such changes made, at least by the very vulnerable, they would
      help, additionally, to protect against other diet-related cancers, especially
      colon cancer and against coronary heart disease.

PMID- 8574865
TI  - Autobiographical experience and word meaning.
AB  - The role of current personal experience in understanding of word meaning was
      investigated in a patient, WM, who suffers from semantic dementia. The study was
      prompted by the observation that WM, despite being severely impaired on formal
      tests of word comprehension and naming, retained a range of vocabulary pertaining
      to her daily life. If autobiographical experience has a general facilitatory
      effect, then this should affect which concepts are retained and which lost, but
      not influence the quality of that conceptual knowledge. Conversely, if personal
      autobiography has a direct role in investing concepts with meaning, then WM's
      understanding of nominal terms that she uses spontaneously in conversation ought
      not to be normal, but should be constrained by the autobiographical context in
      which she uses those terms. WM could define nouns and noun phrases drawn from her
      conversational vocabulary, but her definitions had a markedly autobiographical
      quality. Moreover, WM was extremely impaired in her ability to define new noun
      phrases, constructed by combining words from her conversational vocabulary (e.g.
      "dog licence", constructed from "driving licence" and "dog"; "oil field"
      constructed from "oil" and "field"). It was concluded that WM does not have
      normal conceptual understanding of nouns and noun phrases that she uses
      appropriately in conversation. Her understanding is narrow and autobiographically
      constrained. The findings, which suggest an interactive relationship between
      autobiographical and semantic memory, have implications for understanding of the
      progressive breakdown of semantic knowledge.

PMID- 8574867
TI  - Refractory semantics in global aphasia: on semantic organisation and the access
      storage distinction in neuropsychology.
AB  - A single case study is reported of a global aphasic patient, JM, with impaired
      access to semantic information which was particularly severe for the class of
      proper names. JM's ability to perform matching tasks with printed words and
      pictures to auditory words deteriorated when items were repeated, especially when
      the response-stimulus interval was short. Performance was also inconsistent
      across items. The effect of repeated testing on items generalised to other,
      previously untested members of the same category. Despite this, JM was able to
      access general semantic information about stimuli from the affected categories
      (e.g. to categorise boys' and girls' names), and showed good ability to access an
      input lexicon concerning these stimuli. There was also a close relationship
      between the categories affected when he was tested with pictures and printed
      words. We propose that JM's deficit can be attributed to his semantic system
      entering an abnormal refractory state once semantic access for a particular item
      has been achieved, and with this stage being isolated from the procedures
      providing access to stored lexical knowledge. Furthermore, the representations
      affected seem common to pictures and printed words. We discuss the implications
      of the results for understanding the nature of semantic representations in
      general and for proper names in particular, and for the distinction between
      access and storage deficits in neuropsychology.

PMID- 8574866
TI  - Neuroanatomical correlates of category-specific semantic disorders: a critical
      survey.
AB  - Previous studies of category-specific semantic disturbances have focused their
      attention on the intrinsic cognitive structure of these disorders. The present
      survey aims to evaluate the relationships between disrupted semantic category and
      localisation of the underlying brain damage, in order to establish whether the
      injured brain areas house just those neurophysiological mechanisms that should
      have critically contributed to the acquisition of the disrupted semantic
      categories. We took into account in our review two double dissociations
      concerning respectively: (1) the impairment of a specific linguistic category--we
      contrast those disorders selectively affecting verbs (action names) with those
      selectively affecting nouns (object names); (2) the impairment of a specific
      conceptual/semantic domain--we contrast disorders selectively affecting living
      beings with those preferentially affecting man-made artefacts. The hypothesis
      that different categories of knowledge may be closely intertwined with different
      sources of sensory-motor information, was substantially confirmed. The lesion
      preferentially encroached on the left frontal lobe when the category "verbs" was
      selectively affected; it involved the left temporal lobe and the posterior
      association areas when the category "nouns" was preferentially disrupted; it
      involved bilateral temporo-limbic structures and inferior temporal lobes when the
      category "living beings" was selectively disrupted; it usually encroached on the
      left fronto-parietal areas when man-made artefacts and body parts were
      preferentially affected. These data support the hypothesis that: (a) action
      schemata may critically contribute to the development of the semantic
      representation of verbs, (b) mechanisms of sensory integration may play an
      important role in establishing the semantic representation of nouns; (c) high
      level visual processing and multi-modal sensory convergency may critically
      contribute to organising the semantic representation of living beings; (d) motor
      kinaesthetic integration may play a leading role in developing the semantic
      representation of man-made artefacts.

PMID- 8574868
TI  - Towards a unitary account of access dysphasia: a single case study.
AB  - We report the case of a patient, H.E.C., with a profound verbal comprehension
      impairment. His comprehension impairment involved both common names (animal and
      inanimate items) and proper names. Within the proper name category, his
      comprehension of country and famous peoples' names was better than his
      comprehension of common forenames. By using matching to sample techniques,
      H.E.C.'s impairment was found to be affected by presentation rate and by semantic
      relatedness, but not by word frequency. An analysis of his responses showed
      marked inconsistency and serial position effects (i.e. a decrement of performance
      on subsequent presentations of the same items). H.E.C.'s comprehension deficit
      was interpreted in terms of an "access" impairment within the word-meaning
      system. A unitary account of this impairment in terms of a deficit that delays
      the return, following activation, of the set of representations underlying a
      word, to a "ready state" is proposed.

PMID- 8574869
TI  - The compositionality of lexical semantic representations: clues from semantic
      errors in object naming.
AB  - We present evidence that semantic errors in object naming can arise not only from
      impairment to the semantic system but also from damage to input and output
      processes. Although each of these levels of disruption can result in similar
      types of semantic errors in object naming, they have different types of
      consequences for performance on other lexical tasks, such as comprehension and
      naming to definition. We show that the analysis of the co-occurrence of semantic
      errors in naming with different patterns of performance in other lexical
      processing tasks can be used to localise the source of semantic errors in the
      naming process. Finally, we argue that the similarity of semantic errors in
      object naming, resulting from damage to different components of the naming
      processes by which they are activated by visual input, as well as the processes
      by which they activate output representations.

PMID- 8574870
TI  - Investigating semantic memory impairments: the contribution of semantic priming.
AB  - The semantic priming task is a valuable tool in the investigation of semantic
      memory impairments in patients with acquired disorders of language. This is
      because priming performance reflects automatic or implicit access to semantic
      information, unlike most other tests of semantic knowledge, which rely on
      explicit, voluntary access. Priming results are important for two main reasons:
      First, normal priming results may be observed in patients who perform poorly on
      other semantic memory tests, enabling us to distinguish between loss of, or
      damage to, information in semantic memory, and voluntary access to that
      information. Second, we can investigate the detailed pattern of loss and
      preservation of different types of semantic information, by charting the priming
      effects for different kinds of words, and different kinds of semantic relations
      between primes and targets. We discuss the use of the priming task in this
      context, and address some of the theoretical and methodological criticisms that
      have been raised in connection with use of the priming task to address these
      issues. We then describe two recent studies in which we have employed semantic
      priming tasks, along with other more traditional methods, to investigate specific
      questions about the semantic memory deficits of three patients.

PMID- 8574871
TI  - Probing sensory and associative semantics for animals and objects in normal
      subjects.
AB  - Neuropsychological studies of patients with "category-specific" semantic memory
      disorders have fuelled a debate concerning the organisation of knowledge. In
      particular it has been suggested that the reported double dissociation between
      knowledge of animals and living things on the one hand, and objects on the other,
      reflects a more fundamental division of semantic representation into functional
      associative and sensory-visual domains. The present study attempted to
      investigate whether there were systematic differences along these dimensions in
      normal subjects using a sentence-verification technique. It was found that
      response times were significantly longer for verification of statements
      concerning the sensory attributes of objects than for statements about their
      associative attributes. In the case of animals, there were no differences in
      response latency to associative or sensory statements. In the light of this
      previously unreported fractionation within verbal semantics, the possible
      consequences for models of semantic memory are discussed.

PMID- 8574872
TI  - Naming without knowing and appearance without associations: evidence for
      constructive processes in semantic memory?
AB  - This study describes a patient (SE) with temporal lobe injury resulting from
      Herpes Simplex Encephalitis, who displayed a previously unreported impairment in
      which his knowledge of associative and functional attributes of animals was
      disproportionately impaired by comparison with his knowledge of their sensory
      attributes (including their visual properties and characteristic sounds). His
      knowledge of man-made objects was preserved. A striking aspect of the present
      case was that the patient remained able to name many animals from their pictures,
      despite making gross errors in generating associative information about these
      same animals. This suggests that a semantic representation incorporating stored
      sensory knowledge may be sufficient for naming (at least for biological
      categories) and associative information may be unnecessary. Semantic knowledge
      may normally incorporate more information than is necessary for identification.
      SE's errors were found to be confabulatory and reconstructive in nature and it is
      argued that this aspect of his performance challenges passive conceptions of
      semantic memory couched in terms of a catalogue of stored representations. It is
      proposed that the patient's disorder affects a dynamic, constructive, and
      inferential component of his knowledge base, and that this component is sensitive
      to semantic category.

PMID- 8574873
TI  - Selective impairments of object knowledge in a case of acquired cortical
      blindness.
AB  - A patient (N.B.) is described, who displays distinct deficits of object knowledge
      related to knowledge type (Functional/Associative vs Visual) and also to
      knowledge category (Animate vs Inanimate). The patient was first given an orally
      presented forced-choice test devised to assess orthogonal combinations of
      knowledge type and knowledge category. In the production of this test it was
      found that normals took longer to respond to Visual questions than to
      Functional/Associative questions; therefore, sets of questions were compiled that
      were matched for both accuracy and latency. There were two main findings
      concerning N.B.'s semantic memory. First, with careful matching of difficulty
      level, the patient showed selective preservation of Functional/Associative
      knowledge of Animate objects compared with Visual knowledge of Animate objects
      and also compared with Functional/Associative knowledge of Inanimate objects.
      Second, there was a qualitative difference in patterns of knowledge retrieval for
      Visual compared with Functional/Associative knowledge. Retrieval of Visual
      knowledge, both Animate and Inanimate, was inconsistent and, in a word-pair
      recall test, a high degree of connection of a Visual property to an object did
      not promote paired-associate learning. In contrast, retrieval of
      Functional/Associative knowledge (both Animate and Inanimate) was consistent and
      paired-associate learning was influenced by connection strength. This study
      provides strong evidence to support the validity of both "knowledge type" and
      "category" based accounts of the organisation of semantic memory.

PMID- 8574874
TI  - Charting the progression in semantic dementia: implications for the organisation
      of semantic memory.
AB  - A patient, JL, with the syndrome of semantic dementia was assessed longitudinally
      over a two-year period. The data presented here address the controversy
      concerning the hierarchical organisation of semantic memory. On a range of
      category fluency tests, when first tested JL was just within the normal range on
      the broadest categories of animals and household items, but was virtually unable
      to produce any instances of specific categories such as breeds of dog or musical
      instruments. Longitudinal fluency data for the animal category demonstrate that
      while JL continued to produce the most prototypical responses (cat, dog, horse),
      other animal labels dropped out early from his vocabulary. On the picture-sorting
      tests from our semantic memory test battery, JL's discrimination between living
      things and man-made objects was preserved for a substantial time in conjunction
      with a marked decline in his sorting ability for more specific categories,
      particularly features or attributes (e.g. size, foreign-ness, or ferocity of
      animals). An analysis of naming responses to the 260 Snodgrass and Vanderwart
      pictures on four occasions suggests a progressive loss of the features of
      semantic representations that enable discrimination between specific category
      instances. There was a progressive decline in circumlocutory and category co
      ordinate responses with a rise in broad superordinate and cross-category errors.
      The latter are of particular theoretical interest; on session I, all cross
      category errors respected the living/man-made distinction, but by session IV
      almost half of such errors failed to respect this distinction. The emergence of
      category prototypes was another notable feature, particularly in the living
      domain: at one stage, land (or four-legged) animals were all named either cat,
      dog, or horse. By contrast, within the man-made domain, items were frequently
      described in terms of their broad use or function, until eventually no defining
      features were produced. These findings are discussed in the context of competing
      theories of semantic organisation.

PMID- 8574875
TI  - Objects and properties: a study of the breakdown of semantic memory.
AB  - This paper reports a study of the breakdown of semantic memory in the case of a
      subject with semantic dementia. The first experiment shows that the subject
      failed to comprehend words of low familiarity and word frequency, even though the
      spoken word forms were recognised as familiar. Experiments 2 and 3 showed (a)
      that the recall of word meanings in definition tasks did not vary with the
      generality of the word meaning (e.g. category, basic level, or subordinate
      property) but varied instead with the concept familiarity and frequency of the
      name; (b) that the ability to verify properties of basic-level objects was not
      affected by the ability to comprehend the property name, but depended instead on
      the degree of knowledge demonstrated for the object name in definition tasks; (c)
      that properties were frequently verified correctly when the object had been
      defined only to the superordinate level. It is argued that the results do not
      support the widely held view that, in general, specific information is lost first
      when semantic memory breaks down. The selective failure to recall specific
      information for some word meanings is discussed with reference to two theoretical
      accounts.

PMID- 8574876
TI  - Preservation of categorical knowledge in Alzheimer's disease: a computational
      account.
AB  - The distinction between knowledge of specific exemplars and knowledge of their
      general categories is central to much theorising on the nature of semantic
      memory. The dissociation between exemplar and category knowledge observed in
      Alzheimer's Disease (AD) would appear to support this distinction, and to suggest
      that different neural systems are involved in the representation of exemplar and
      category knowledge. We review the evidence for preserved category knowledge in
      the semantic memory impairment of AD, and propose an alternative interpretation,
      according to which category and exemplar knowledge are both represented in the
      same distributed neural substrate. The relative preservation of category
      knowledge is a consequence of the greater frequency, and hence greater
      robustness, of the representation of attributes shared by all or most members of
      a category, compared to exemplar-unique attributes. We test and confirm the
      computational adequacy of this hypothesis in two computer simulations.

PMID- 8574877
TI  - An interactive activation approach to object processing: effects of structural
      similarity, name frequency, and task in normality and pathology.
AB  - We present a computational model of the processes involved in retrieving stored
      semantic and name information from objects, using a simple interactive activation
      and competition architecture. We simulate evidence showing a cross-over in normal
      reaction times to make semantic classification and identification responses to
      objects from categories with either structurally similar or structurally
      dissimilar exemplars, and that identification times to objects from these two
      different classes correlate differentially with measures of the structural
      similarity of objects within the category and the frequency of the object's name.
      Structural similarity exerts a negative effect on object decision as well as
      naming, though this effect is larger on naming. Also, on naming, structural
      similarity interacts with the effects of name frequency, captured in the model by
      varying the weight on connections from semantic to name units; frequency effects
      are larger with structurally dissimilar items. In addition, (1) the range of
      potential errors for objects from these two classes, when responses are elicited
      before activation reached a stable state, differ--a wider range of errors occur
      to objects from categories with structurally similar exemplars; and (2) simulated
      lesions to different locations within the model produce selective impairments to
      identification but not to semantic classification responses to objects from
      categories with structurally similar exemplars. We discuss the results in
      relation to data on visual object processing in both normality and pathology.

PMID- 8574878
TI  - Cell adhesion molecules 1: immunoglobulin superfamily.

PMID- 8574879
TI  - Retinopathy of prematurity: perspective for the nineties.
AB  - In any discussion of the eye problems of the premature retinopathy of prematurity
      is today the major problem. Four areas where progress is needed suggest
      themselves. Further work needs to be done on the International Classification of
      Retinopathy of Prematurity (ICROP), particularly with regard to Zone 2 disease
      where 75% of the disease is concentrated. Treatment of Zone 1 disease is the next
      important area in terms of its outcome and the critical question of whether to
      use cryotherapy or laser. The third area which needs open discussion is the
      problem of screening prematures in excess of 1250 g birth weight and 32 weeks
      gestational age. In the United States, this constitutes hundreds of thousands of
      infants and is well beyond the capabilities of the ophthalmic community
      interested and knowledgeable in the techniques of examining these premature eyes.
      Finally, the other important area is the striking difference between the infant
      of today and the infant of the previous 'epidemic' of the forties and fifties.

PMID- 8574880
TI  - Update on strabismus and amblyopia.
AB  - This review analyzes progress in the field of infantile strabismus and amblyopia.
      Only works which are of clinical interest have been reviewed. A brief survey is
      provided also of subjects matter of international debate, as surgery for
      accommodative esotropia, the prism adaptation test and the use of sectors for
      amblyopia treatment. Mention is made of new developments in the field which are
      not yet applicable to clinical practice. Finally, progress in the approach
      towards ocular nystagmus is considered as well.

PMID- 8574881
TI  - Screening for ocular dysfunction in children: approaching a common program.
AB  - According to the general principles of screening, detection of visual impairment
      in children is worthwhile, since the condition is a serious health problem,
      reliable diagnostic tests are available and effective treatment is possible in
      most instances of ocular and visual dysfunction. However, an evaluation of the
      screening procedures has not been properly done and the cost-benefit of screening
      has not been studied. The aim of the present study is to perform a systematic
      analysis of the screening programs for detection of visual dysfunction. In the
      screening two parts can be separated, one that concerns the more serious ocular
      and visual conditions which have to be discovered by general survey methods very
      early in life, and one that involves detection of less serious conditions, mainly
      amblyopia, which can be diagnosed by testing for monocular reduction of visual
      acuity at about 3-4 years of age. The performance characteristics of the
      screening programs used in Sweden and Canada were evaluated and found to be very
      favourable. Based on the analysis and the evaluation, recommendations are made on
      programs for vision screening in children that could be applied more widely. The
      program could involve all or parts of the following: 1) A careful inspection of
      the eyes in the neonatal period and preferably also examination of the red reflex
      with the ophthalmoscope. 2) Children at high risk for ocular and visual disorder,
      i.e. those born prematurely before 32 weeks of age, or with genetic disease,
      hearing deficit and/or neurological and mental disorder, should be examined at
      the proper age by an ophthalmologist. 3) All staff at pediatric departments and
      child health care centers should be familiar with the visual development of the
      normal baby and should be alerted to the various symptoms and signs which first
      warn parents that there may be a visual defect. An inspection of the eyes to
      detect squint should be part of all pediatric examinations. 4) A screening test
      of monocular visual acuity in 4 year-old children can be reliably performed by
      non-ophthalmic personnel after proper training. The screening test should be
      repeated by school nurses during the first grade of school, and at regular
      intervals during the school years. 5) The children that screen positively should
      be seen by ophthalmologists, and in some cases by orthoptists, without undue
      delay for diagnosis and treatment.

PMID- 8574882
TI  - Ocular anomalies: embryological implications.

PMID- 8574884
TI  - Localization of D-amino acid oxidase mRNA in the mouse kidney and the effect of
      testosterone treatment.
AB  - D-Amino acid oxidase (DAO), which catalyzes oxidative deamination of D-amino
      acids, is known to be highly expressed in the kidney. This study was designed to
      examine the localization of DAO mRNA in the mouse kidney using in situ
      hybridization histochemistry (ISH). For comparison, ISH for mRNA of ornithine
      decarboxylase (ODC), which is also highly expressed in the mouse kidney, was
      simultaneously performed. Adult, male mice which received 1 mg of testosterone
      propionate or vehicle injection, were sacrificed 14 h after injection and their
      kidneys were removed and processed for ISH. Hybridization signals for both mRNAs
      were exclusively located over the epithelial cells of the proximal tubule in the
      vehicle-treated animals. Signals for the DAO mRNA were observed at nearly the
      same hybridization intensity throughout the proximal tubule, whereas
      hybridization signals for the ODC mRNA were observed exclusively in the pars
      convoluta. Following testosterone treatment, ODC mRNA in the pars convoluta was
      expressed with a stronger intensity than that in the vehicle-injected animals.
      ODC mRNA was also expressed in the pars recta with a weaker intensity than in the
      pars convoluta. On the other hand, DAO mRNA expression was little affected by
      testosterone treatment. These results indicate that, although both genes are
      possibly expressed in the same cells, the expression of these genes is regulated
      by different mechanisms.

PMID- 8574883
TI  - Immunohistological localization of regulatory peptides in the midgut of the
      female mosquito Aedes aegypti.
AB  - The midgut of the female mosquito Aedes aegypti was studied immunohistologically
      with antisera to various regulatory peptides. Endocrine cells immunoreactive with
      antisera to perisulfakinin, RFamide, bovine pancreatic polypeptide, urotensin 1,
      locustatachykinin 2 and allatostatins A1 and B2 were found in the midgut.
      Perisulfakinin, RFamide and bovine pancreatic polypeptide all react with the
      same, about 500 endocrine cells, which were evenly distributed throughout the
      posterior midgut, with the exception of its most frontal and caudal regions. In
      addition, these antisera recognized three to five neurons in each ingluvial
      ganglion and their axons, which ran longitudinally over the anterior midgut, as
      well as axons innervating the pyloric sphincter. The latter axons appear to be
      derived from neurons located in the abdominal ganglia. Antisera to two different
      allatostatins recognized about 70 endocrine cells in the most caudal area of the
      posterior midgut and axons in the anterior midgut whose cell bodies were probably
      located in either the brain or the frontal ganglion. Antiserum to
      locustatachykinin 2 recognized endocrine cells present in the anterior midgut and
      the most frontal part of the posterior midgut, as well as about 50 cells in the
      most caudal region of the posterior midgut. Urotensin 1 immunoreactivity was
      found in endocrine cells in the same region as the perisulfakinin-immunoreactive
      cells, but no urotensin-immunoreactive axons were found in the midgut. Double
      labeling experiments showed that the urotensin and perisulfakinin
      immunoreactivities were located in different cells. Such experiments also showed
      that the locustatachykinin and allatostatin immunoreactivities in the most caudal
      area of the posterior midgut were present in different cells. No immunoreactivity
      was found in the mosquito midgut when using antisera to corazonin, allatropin or
      leucokinin IV. Since these peptides have either been isolated from, or can
      reasonably be expected to be present in mosquitoes, it was concluded that these
      peptides are not present in the mosquito midgut.

PMID- 8574885
TI  - Hamster pulmonary endocrine cells with neural cell adhesion molecule (NCAM)
      immunostaining.
AB  - Pulmonary endocrine cells of Syrian golden hamster were stained for neural cell
      adhesion molecule (NCAM) with indirect fluorescent immunostaining and observed
      with a confocal laser scanning microscope equipped with an argon laser. Sections
      100 microns thick of hamster lung fixed with phosphate-buffered 4%
      paraformaldehyde were prepared. The sections were incubated with rat monoclonal
      antibody against NCAM, followed by fluorescence-labeled antibody against rat
      immunoglobulin. Some were doubly immunostained for NCAM and one of the following
      endocrine markers: neuron-specific enolase, calcitonin gene-related peptide and
      serotonin. Expression of NCAM in the hamster airway epithelium was seen in cell
      nests resembling neuroepithelial bodies (NEBs). NCAM immunostaining was positive
      at the lateral cell borders between the cells composing the nest, but negative at
      the border with the adjacent, presumably non-endocrine cells. Double
      immunostaining confirmed that the grouped cells with NCAM immunoreactivity were
      of an endocrine nature, but that single endocrine cells did not show NCAM
      immunoreactivity. An electron microscopic study with NCAM immunostaining
      confirmed the light microscopic study. These suggest that NCAM expression could
      be important for the morphogenesis of NEBs. A confocal laser microscope was used
      to make three-dimensional images of NEBs after NCAM immunostaining and the
      spatial interaction between NEBs and the surrounding microenvironment was
      studied.

PMID- 8574886
TI  - Detection of mammosomatotroph cells and identification of the coexistence of
      growth hormone and prolactin within the same secretory granules in these cells
      using confocal laser scanning microscopy.
AB  - This study was designed to examine whether mammosomatotroph cells (MS cells) can
      be easily detected using confocal laser scanning microscopy (CLSM) and whether
      the coexistence of growth hormone (GH) and prolactin (PRL) within the same
      secretory granule can be identified in the MS cell using CLSM. Conventional epoxy
      resin-embedded tissues of mixed GH- and PRL-secreting human pituitary adenomas
      were used for this double-labelling immunofluorescent study by CLSM. A semithin
      section of the tissue after plastic removal and bleaching was
      immunohistochemically double-stained with primary antibodies against GH and PRL,
      followed by secondary antibodies conjugated with Rhodamine (GH) and FITC (PRL).
      MS cells simultaneously showing fluorescence of both Rhodamine and FITC were
      easily detected by CLSM at lower magnification. At higher magnification, the
      coexistence of Rhodamine and FITC on the same secretory granule was identified by
      using a superimposed display. This finding was confirmed by immunoelectron
      microscopy. The CLSM technique may be useful for the study of MS cells.

PMID- 8574887
TI  - Proteoglycans associated with the ciliary zonule of the rat eye: a histochemical
      and immunocytochemical study.
AB  - The structural organization of integral and associated components of the ciliary
      zonule is still not fully understood. The present study is to localize and
      characterize the proteoglycans associated with the ciliary zonule of the rat eye
      by Cuprolinic blue (CB) staining and immunocytochemistry. After CB staining, the
      proteoglycans appeared as electron dense elongated rodlets and were localized
      with the zonular fibers. They were seen lying on the periphery of the zonular
      fibers or along the length of the individual fibrils. Most of the CB rodlets had
      a size of 60-170 nm long (average 130 nm) and 25 nm wide. Smaller CB rodlets
      measuring 25-60 nm long (average 45 nm) and 12 nm wide were sometimes found
      associated with the individual zonular fibrils. The CB rodlets were removed after
      chondroitinase ABC or chondroitinase AC treatment, but were resistant to
      heparitinase, nitrous acid, keratanase or Streptomyces hyaluronidase digestions.
      The ciliary zonule was also immunostained with three monoclonal antibodies: 2-B-6
      specific for chondroitin 4-sulfate, 3-B-3 for chondroitin 6-sulfate and 1-B-5 for
      unsulfated chondroitin, using indirect immunoperoxidase or immuno-colloidal gold
      methods. The zonular fibers were immunoperoxidase stained and immunogold labeled
      by 2-B-6, but were not reactive to 3-B-3 and 1-B-5. The results demonstrate that
      chondroitin sulfate proteoglycan is associated with the ciliary zonule of the rat
      eye.

PMID- 8574888
TI  - Immunocytochemical distribution of E-cadherin in normal and injured lung tissue
      of the rat.
AB  - Affinity purified rabbit anti-mouse E-cadherin antibodies, reacting with diverse
      rat epithelia, were used to characterize epithelial changes in a radiation
      induced fibrosis model of rat lung by immunoblotting techniques, immunoperoxidase
      and immunofluorescence microscopy. Immunostaining of normal rat lung tissues
      revealed a predominant staining of type II pneumocytes. Immunoelectron microscopy
      confirmed the immunohistochemical data of normal lung tissue obtained at the
      light microscopic level. In severely injured rat lung, we found enhanced
      immunoreactivity for E-cadherin at the surface of type I alveolar epithelial
      cells. The results suggest that E-cadherin is an adhesion molecule that is
      modulated after pathological alteration of the alveolar epithelium and that the
      antiserum may be useful for the characterization of normal and diseased rat
      epithelia.

PMID- 8574889
TI  - Cell-cycle-dependent gene expression studied by two-colour fluorescent detection
      of a mRNA and histone mRNA.
AB  - We investigated whether a probe specific for histone H3 mRNA could be used as a
      marker to study cell-cycle dependency of gene expression by double-fluorescent
      RNA in situ hybridization (FISH). First, we showed that all S-phase cells in cell
      cultures having incorporated BrdU revealed histone H3 mRNA expression by RNA
      FISH, indicating that histone H3 expression is a reliable marker for S-phase
      cells. Second, we analysed whether the expression of human cytomegalovirus
      immediate early genes in rat 9G cells, which are known to be induced in an S
      phase dependent way by cycloheximide, correlated with the expression of histone
      H3 mRNA. Double-hybridization experiments with a digoxigenin-labelled probe for
      IE mRNA and a fluoresceinated probe for histone H3 mRNA revealed that cells
      expressing IE mRNA also expressed histone H3 mRNA. Third, we examined the cell
      cycle dependency of luciferase gene expression in X1 cells. Luciferase mRNA is
      heterogeneously expressed in X1 cell cultures, but cells expressing luciferase
      did not necessarily express histone H3 mRNA. This indicates that luciferase gene
      expression in X1 cells is not induced during S-phase. The results of our study
      show that histone H3 mRNA expression can be successfully used as a marker to
      establish cell-cycle dependency of gene expression by double-RNA FISH.

PMID- 8574891
TI  - The use of the digital cell image analysis of Feulgen-stained nuclei to detect
      apoptosis.
AB  - Cell death is an essential event in the functioning of multicellular organisms.
      It plays a role opposite to that of mitosis in the regulation of cell
      populations. In the present work, we describe an original methodology which
      permits the easy detection and count of apoptotic cells in a given tissue. This
      methodology is based on the digital cell image analysis of Feulgen-stained
      nuclei, which also permits the calculation of the proliferation index, i.e. the
      percentage of cells in the S phase of the cell cycle. This percentage of cells in
      the S phase is strongly related to the mitotic index. Our methodology, which
      involves the multivariate analysis of 14 morphonuclear parameters computed by
      means of the digitized cell image analysis of Feulgen-stained nuclei, was applied
      here to a well-known biological apoptosis model, namely glucocorticoid-treated
      rat thymocytes. The parameters that permitted the detection of apoptotic cells
      were the integrated optical density, a parameter that describes the nuclear DNA
      content, and the run length percentage and long run length parameters which are
      related to the pattern of chromatin condensation. This determination can be
      carried out on a relatively small number of cells.

PMID- 8574890
TI  - Immunohistochemical evidence for loss of ICAM-1 by alveolar epithelial cells in
      pulmonary fibrosis.
AB  - ICAM-1 is an intercellular adhesion molecule of the immunoglobulin supergene
      family involved in adherence of leukocytes to the endothelium and in leukocytic
      accumulation in pulmonary injury. In the current study, the antigen retrieval
      technique was used to detect ICAM-1 immunohistochemically in paraffin sections of
      lungs from human, mouse and rat as well as in bleomycin- or radiation-induced
      fibrotic lungs from rat and human. In normal lung tissue, the expression of ICAM
      1 on alveolar type I epithelial cells is stronger than on alveolar macrophages
      and on endothelial cells. Preembedding immunoelectron microscopy of normal rat,
      mouse and human lung samples revealed selective ICAM-1 expression on the surface
      of type I alveolar epithelial cells and, to a lesser extent, on the pulmonary
      capillary endothelium and on alveolar macrophages. In fibrotic specimens, both
      focal lack and strengthening of immunostaining on the surface of type I cells was
      found. Alveolar macrophages were found focally lacking ICAM-1 immunoreactivity.
      In some cases, rat type II pneumocytes exhibited positive immunoreactions for
      ICAM-1. Immunoelectron microscopy with preembedded rat lungs (bleomycin-exposed
      cases) confirmed the altered ICAM-1 distribution at the alveolar epithelial
      surface. In the alveolar fluid of fibrotic rat lungs, in contrast to that from
      untreated controls, soluble ICAM-1 was detected by western blot analysis.

PMID- 8574892
TI  - High molecular weight DNA from nucleated erythrocytes for use in pulsed-field gel
      electrophoresis (PFGE).
AB  - Nucleated erythrocytes of lower vertebrates provide a source of genomic DNA that
      can be used in pulsed-field gel electrophoresis (PFGE) studies. Difficulties
      reported in the preparation of chicken erythrocyte DNA for analysis by PFGE
      suggest that the presence of hemoglobin iron may result in iron-mediated DNA
      degradation. We report here modifications to the procedures established for
      isolation of high molecular weight DNA from mammalian cells. By increasing the
      volume of buffers and extending the incubation periods to allow for the removal
      of hemoglobin iron, we have successfully prepared channel catfish erythrocyte DNA
      suitable for analysis by PFGE.

PMID- 8574893
TI  - Use of 'long' polymerase chain reaction and magnetic beads for extraction of
      chromosome-specific cDNAs.
AB  - The detection of expressed sequences of genomic DNA is an important aspect of the
      human genome project. A technique is described where 'long' polymerase chain
      reaction (LPCR), which allows for extended large fragment production of > 10-20
      kb, is used with Alu primers to generate a biotinylated template for cDNA
      hybridization. Streptavidin-coated magnetic beads are used to extract the long
      PCR templates and bound cDNAs, which are recovered by standard PCR. This method
      allows the isolation of cDNAs from virtually any human DNA source and should be
      valuable in expression mapping, positional cloning and gene isolation.

PMID- 8574894
TI  - A sensitive method of testing for transgenic mice using polymerase chain reaction
      southern hybridization.
AB  - The polymerase chain reaction (PCR)-based method for identification of small
      numbers (lower than one copy per diploid cell) of transgenes in transgenic mice
      is described. This method is also advantageous in terms of overcoming occasional
      poor PCR conditions.

PMID- 8574895
TI  - Electroporation-mediated transfection of mammalian cells with crude plasmid DNA
      preparations.
AB  - We designed a simple and reproducible electroporation-mediated transfection
      procedure with which to screen mammalian expression vector-constructed cDNA
      libraries. Using a specific chamber composed of five parallel electrodes, the
      recipient cells can be electroporated separately with 40 plasmid DNA preparations
      in a single experiment. Over 300 crude plasmids prepared from E. coli (DH-5)
      carrying a pcD2neo-vector-derived cDNA library were tested. The efficiency of
      stable transfection by electroporation with crude plasmid DNA preparations was 10
      times higher than with the CsCl-purified plasmid DNA. When the crude plasmids
      were digested with RNase, the efficiency of stable transfection markedly
      decreased, indicating that the contaminating bacterial RNA in the crude plasmid
      preparations has a strong carrier effect during the electroporation. Even when
      salmon sperm DNA or genomic DNA from the recipient cells was used as the carrier
      of the purified plasmid, the efficiency was not higher than that using the crude
      preparations. This procedure is useful not only for screening a number of cDNAs
      but also for routinely introducing biologically active foreign genes into
      cultured mammalian cells.

PMID- 8574896
TI  - T-vector cloning and high performance PCR with SuperTth from Thermus
      thermophilus.
AB  - The SuperTth DNA polymerase from Thermus thermophilus exhibits template
      independent terminal transferase (extendase) activity. This enzyme is proposed as
      a cheap alternative for both high performance PCR as well as quick T-vector
      cloning of amplicons, including reverse transcription and cDNA cloning.

PMID- 8574897
TI  - Characterization of a human chromosome 22 enriched bacterial artificial
      chromosome sublibrary.
AB  - Selection of chromosomal sublibraries from total human genomic libraries is
      critical for chromosome-based physical mapping approaches. We have previously
      reported a method of screening total human genomic library using flow sorted
      chromosomal DNA as a hybridization probe and selection of a human chromosome 22
      enriched sublibrary from a total human bacterial artificial chromosome (BAC)
      library (Nucleic Acids Res 1995; 23: 1838-39). We describe here further details
      of the method of construction as well as characterization of the chromosome 22
      enriched sublibrary thus constructed. Nearly 40% of the BAC clones that have been
      mapped by fluorescence in situ hybridization (FISH) analysis were localized to
      chromosome 22. By screening the sublibrary using chromosome 22-specific
      hybridization probes, we estimated that the sublibrary represents at least 2.5 x
      coverage of chromosome 22. This is in good agreement with the results from FISH
      mapping experiments. FISH map data also indicate that chromosome 22-specific BACs
      in the sublibrary represent all the subregions of chromosome 22.

PMID- 8574898
TI  - Construction and utility of a human chromosome 22-specific Fosmid library.
AB  - We have previously demonstrated the capability of the Fosmid vector based on
      Escherichia coli F-factor replicon to stably propagate cosmid-sized human genomic
      DNA fragments. Using the Fosmid vector, we have constructed and arrayed a 10 x
      human chromosome 22-specific library, partly by picking human positive clones
      from a total Fosmid library constructed using DNA from human-hamster hybrid cell
      line containing human chromosome 22, and partly by using flow-sorted chromosomal
      DNA. The clones and physical contig maps of the clones in the library will serve
      as a valuable resource for detailed analysis of the chromosome by providing
      reliable materials for high resolution mapping and sequencing. In order to
      efficiently build physical maps for the chromosomal regions of interest spanning
      several hundred kilobases to a megabase, it is necessary to rapidly identify
      subsets of the Fosmid clones from the library that cover such regions. In this
      report, we describe a method of using random amplification products derived from
      YAC clones to rapidly identify a subset of Fosmid clones that cover a specific
      genomic subregion.

PMID- 8574899
TI  - Endogenous endonuclease hypersensitive sites in Schizosaccharomyces pombe
      chromosomes.
AB  - A novel method was used to characterize the long range susceptibility of
      Schizosaccharomyces pombe chromosomal DNA to endogenous endonuclease cleavage.
      Analyses of pulsed field gel experiments revealed two periodicities in the
      distribution of endogenous endonuclease hypersensitive sites. Endonuclease
      cleavage sites occurred, roughly at 30-509 kilobase pairs (kb) intervals under
      physiological conditions (25 mM KCl). At higher salt concentrations (250 mM KCl
      or 0.2 M and 0.9 M NaCl), endonuclease hypersensitive sites occurred at 200-300
      kb intervals. Endonuclease hypersensitive sites in different chromosomal regions
      were monitored during different stages of the cell cycle. DNA sequencing around
      the endonuclease hypersensitive sites revealed the presence of clusters of A+T
      rich motifs, autonomously replicating sequences (ARSs) in sequences (a
      characteristic of the scaffold-associated regions (SARs) and the presence of a
      CTG trinucleotide at most sites.

PMID- 8574900
TI  - A C. elegans mutant screen based on antibody or histochemical staining.
AB  - A method has been developed for isolating mutations in Caenorhabditis elegans
      that alter antibody or histochemical staining patterns. The basis for this method
      is a new procedure for making C. elegans permeable that does not kill the eggs
      contained within the uterus of gravid adult hermaphrodites. A mutagenized
      population of gravid hermaphrodites is made permeable and then stained with
      either an antibody or a histochemical stain. Animals that stain aberrantly are
      picked to individual petri plates and the eggs within the uterus of the stained
      mother hatch and establish a new genetic line. Antibody and histochemical stains
      are especially useful phenotypes because the staining pattern will usually
      directly reflect the gene expression pattern of the gene that codes for the
      antigen or enzyme. This method was used to isolate mutants that alter the
      expression of a mec-7lacZ fusion gene. Transgenic animals that contained the mec
      7lacZ gene integrated into chromosome I were treated with the mutagen
      ethylmethanesulfonate, allowed to self-fertilize for two generations and then
      stained with X-gal or antibodies against beta-galactosidase. Gravid animals that
      stained abnormally were picked to fresh petri plates and their offspring were
      used to establish new mutant lines.

PMID- 8574901
TI  - Biosynthetic pathways of glycerol accumulation under salt stress in Aspergillus
      nidulans.
AB  - A culture of Aspergillus nidulans (FGSC 359) was gradually adapted for growth in
      media containing up to 2 M NaCl or was exposed to a salt shock with 2 M NaCl. The
      intracellular glycerol level increased by about 7.9-fold in salt-adapted and 2.4
      fold in salt-shocked cultures when compared to the unadapted culture. The
      biosynthetic pathway involved in the accumulation of glycerol was investigated
      under long-term salt adaptation and short-term salt shock. Glycerol-3-phosphate
      dehydrogenase (EC 1.1.1.8) was induced 1.4-fold in salt-shocked but not in salt
      adapted cultures. An alternate enzymatic pathway involving glycerol dehydrogenase
      (NADP(+)-dependent) utilizing dihydroxyacetone (DHA) and/or DL-glyceraldehyde (DL
      GAD) was induced by NaCl. DHA-dependent glycerol dehydrogenase activity was
      induced about 6.3-fold in salt-adapted and 1.35-fold in salt-shocked cultures,
      while DL-GAD-dependent activity was induced about 6.1-fold in salt-adapted and
      1.2-fold in salt-shocked cultures. However, the level of glycerol dehydrogenase
      activity with DL-GAD as substrate was 7% of the DHA-dependent activity. We
      conclude that a salt-inducible NADP(+)-dependent glycerol dehydrogenase activity
      electrophoretically indistinguishable from previously described glycerol
      dehydrogenase I results in glycerol accumulation in salt-stressed A. nidulans.

PMID- 8574902
TI  - Involvement of Candida albicans cell wall proteins in the adherence of
      blastospores to human buccal epithelial cells.
AB  - The adherence of Candida albicans to epithelial cells is one of the first steps
      in the development of candidiasis and therefore could constitute an interesting
      target for the prevention of infection. A yeast cell wall extract was prepared by
      using a C. albicans isolate (IVP 1453) highly adherent to buccal epithelial cells
      (BECs). This cell wall extract was separated by concanavalin A-affinity
      chromatography into two fractions referred to as Fr1 (proteic fraction) and Fr2
      (mannoproteic fraction). The adhesion activity was mostly associated with the
      proteic fraction. This fraction was therefore retained and further fractionated
      by ion-exchange chromatography into two other fractions, referred to as Fr1a and
      Fr1b. The adhesion activity was mostly associated with the Fr1b fraction (56.4%
      adherence inhibition); it was not specific to the C. albicans isolate used during
      the cell wall extract preparation. The Fr1b fraction contained four major
      proteins with molecular masses of 30, 38, 47, and 54 kDa. Among these four
      proteins, those with molecular masses of 38 and 54 kDa could be involved in
      adherence mechanisms of C. albicans to human BECs.

PMID- 8574903
TI  - Extraction and characterization of the insecticidal toxin hirsutellin A produced
      by Hirsutella thompsonii var. thompsonii.
AB  - Hirsutellin A (HtA) produced by Hirsutella thompsonii var. thompsonii (strain JAB
      04) was extracted and purified using a combination of ion-exchange, gel
      permeation, and immunoaffinity chromatography. The identity of the purified HtA
      was confirmed by amino acid analysis and N-terminal sequencing. Monoclonal
      antibodies prepared against HtA were capable of detecting 25-50 ng of HtA by
      direct sandwich ELISA. In addition, utilizing Western blot methods, the
      antibodies were shown to be specific to HtA. The production of HtA was monitored
      during submerged fermentation. The peak level of exocellular HtA (13-14
      micrograms/ml) was during the late exponential growth phase (39-45 h), determined
      by utilizing a combination of densitometric analysis of the 16.3-kDa bands on SDS
      PAGE gels and ELISA. HtA production was directly correlated with mycelial growth.
      Twenty-one-hour culture filtrates were highly toxic to larvae of the greater wax
      moth. Pure HtA at a final concentration of 40 pmol was highly toxic to Galleria
      mellonella larvae.

PMID- 8574904
TI  - Superoxide dismutase: a differentiation protein expressed in Uromyces germlings
      during early appressorium development.
AB  - Germlings of the bean rust fungus Uromyces appendiculatus detect penetration
      sites on the surface of the host leaf by thigmosensing topographical features.
      Within 2-4 min after the apex of a urediospore germ tube encounters the cuticular
      lip of a stomate, the germling ceases polarized growth and begins to swell over
      the aperture. The mechanism by which the cells detect topographical signals is
      not understood; however, previous experiments indicated that the initiation
      process does not involve de novo gene expression. In order to detect
      posttranslational modifications, the protein profiles of induced and noninduced
      germlings were compared at the earliest stages of appressorium formation, and a
      21-kDa differentiation protein was identified by a shift in isoelectric point.
      The N-terminal amino acid sequence exhibited homology with superoxide dismutase
      (SOD), and antibodies to a synthetic peptide fragment of the respective sequence
      recognized cooper/zinc isozymes of SOD in electroblots of native gels.
      Electroelution of the active enzyme bands and separation by SDS-PAGE indicated
      that the 21-kDa protein is a component of a tetrameric 85-kDa SOD.

PMID- 8574905
TI  - A unique repeated DNA sequence in the cyclosporin-producing strain of
      Tolypocladium inflatum (ATCC 34921).
AB  - Recombinant lambda clones containing repeated DNA sequences were isolated from
      the cyclosporin A-producing fungus Tolypocladium inflatum (ATCC 34921) by
      differential hybridization with total fungal DNA and rDNA probes. From this
      survey 1% of the lambda clones appeared to contain repeated sequences. Subsequent
      analysis led to the identification of a dispersed repetitive DNA element. It was
      named CPA element (cyclosporin production associated) and appears to be strain
      specific, since it is absent from other related strains or fungi. Hybridization
      with chromosomal restriction fragments indicates an equal distribution of the CPA
      element in the genome. The copy number was estimated to be between 20 and 30 per
      haploid genome. Sequence analysis of a 0.9-kb XhoI fragment from three copies of
      the CPA element revealed strong conservation of this sequence among all copies. A
      200-bp region exhibits similarities to a repeated sequence from Zea
      diploperennis. The use of this DNA sequence as a molecular marker for
      identification of this cyclosporin-producing strain ATCC 34921 is discussed as is
      the relevance of repeated DNA sequences for rearrangements of fungal karyotypes.

PMID- 8574907
TI  - A suppressor mutation which suppresses adenylyl cyclase mutations in Neurospora
      crassa.
AB  - A spontaneous suppressor mutant, hah, which suppressed the colonial growth of
      adenylyl cyclase mutants (cr-1) was isolated. The morphology of cr-1 hah was
      filamentous, but slightly different from that of wild type on solid medium. The
      hah strain formed many high aerial hyphae, but did not form any conidia. The
      expression levels of an adenylyl cyclase gene, nac, in both hah and cr-1 hah were
      much higher than those in wild type or in cr-1. The level of cAMP in cr-1 was
      very low but returned to close to the wild-type level in the cr-1 hah suppressed
      strain, whereas that in the strain carrying hah alone was similar to or a little
      higher than that in wild type. The hah gene was located 13.3 map units from in1
      on the right arm of the linkage group V. The hah mutation was recessive and
      allele specificity of hah for the suppression of cr-1 mutations was weak.

PMID- 8574906
TI  - Osmotic effects on the polyamine pathway of Neurospora crassa.
AB  - In bacteria, mammals, and certain plants, the induction of the polyamine
      synthetic enzyme, ornithine decarboxylase (ODC), and the accumulation of its
      product, putrescine, follows osmotic manipulations of cells. In at least some of
      these cases, this response is indispensable for survival. We wished to determine
      whether the polyamine pathway of Neurospora crassa was regulated in response to
      hyper- or hypoosmotic conditions. Unlike ODC of most other classes of organisms,
      the N. crassa enzyme and the accumulation of putrescine appears to be relatively
      indifferent to these conditions, either during sudden transitions or in steady
      state. We conclude that other mechanisms of osmotic adjustment or tolerance have
      evolved in N. crassa and perhaps other fungi that obviate the need for putrescine
      accumulation.

PMID- 8574908
TI  - Recovery of gastrointestinal motility from post-operative ileus in dogs: effects
      of Leu13-motilin (KW-5139) and prostaglandin F2 alpha.
AB  - Cyclical motor activity of the gastrointestinal tract, normally occurring during
      the interdigestive period in several mammals, is disrupted in the post-operative
      ileus. We determined the recovery from the disappearance of cyclical motor
      activity, from the stomach to the colon, in dogs after laparotomy with the force
      transducers. Moreover, we examined the effects of Leu13-motilin (KW-5139) and
      prostaglandin F2 alpha (PGF2 alpha), administered in the early post-operative
      period, on the gastrointestinal motility. Following laparotomy, the cyclical
      motor activity reappeared firstly in the ileum and the colon, then in the jejunum
      and the duodenum, and finally in the stomach. The reappearance time of the phase
      III contractions in the stomach was 105.8 +/- 10.6 h (n = 4). In the early post
      operative period, KW-5139 (0.5 microgram kg-1, i.v.) induced phase-III-like
      contractions, whereas PGF2 alpha (50 micrograms kg-1, i.v.) induced
      simultaneously occurring contractions over the whole gastrointestine. The
      treatment with KW-5139 (0.5 microgram kg-1, i.v.) four times (twice daily on the
      first and the second post-operative day) significantly (P < 0.05) shortened the
      time required to recover the phase III contractions in the stomach (64.2 +/- 2.2
      h, n = 4), whereas that with PGF2 alpha (50 micrograms kg-1, i.v.) four times did
      not (111.3 +/- 17.2 h, n = 4). The present results indicate that, after
      laparotomy, the cyclical motor activity recovers faster in the distal intestine
      than in the proximal intestine and the stomach, and that KW-5139, but not PGF2
      alpha, shortens the reappearance time of the phase III activity in the stomach.

PMID- 8574909
TI  - Effects of absorption rate, flow rate and fluid load on colonic motor activity in
      dogs.
AB  - We investigated the relationship between absorption rate, flow rate, fluid load
      and colonic motor activity in an in vivo isolated colonic loop model. Motor
      activity was recorded by implanted strain gauge transducers. Two electrolyte
      solutions were perfused at 0.4 and 1.6 mL min-1 through the open colonic loop
      (distal end open) or infused into the closed loop (distal end closed). The first
      solution resembled ileostomy fluid (ES1) and the second solution was an iso
      osmolar mannitol solution (ES2). The absorption rate for H2O measured by 14C PEG
      concentrations of ES2, 0.2 +/- 0.03 mL min-1, was significantly less than that of
      ES1, 0.6 +/- 0.06 mL min-1. Infusion of ES1 under open loop conditions served as
      control. Motor activity was analysed for area under contractions and expressed as
      motor index ratio in comparison to the control. None of the solutions altered
      motor activity when perfused at the two rates through the open loop. Under closed
      loop conditions, the infusion of either solution at 0.4 mL min-1 had no
      significant effect on colonic motor activity. Infusion of ES1 or ES2 at 1.6 mL
      min-1 into the closed loop, however, increased the motor index ratio 2.5-fold and
      3.6-fold, respectively (P < 0.01). The proximal half of the colon was less
      affected than the distal half during infusion of ES1 but not during infusion of
      ES2. We conclude that flow rate and absorption rate do not influence colonic
      motor activity as long as the fluids can leave the colon. When the distal end is
      closed, inflow, resulting in fluid accumulation and distension, leads to
      stimulation of colonic motor activity.

PMID- 8574910
TI  - Functional role and histological demonstration of nitric-oxide-mediated
      inhibitory nerves in dog sphincter of Oddi.
AB  - Nitric oxide (NO) plays an important physiological role in regulating
      gastrointestinal motility. Involvement of endogenous NO was evaluated in the
      response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog
      sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10(
      5) M) and K+ (10 mM) produced only a relaxation in the sphincter muscle strips
      contracted with substance P, which was not potentiated by atropine. The TES
      induced relaxation was abolished by tetrodotoxin (3 x 10(-7) M) and
      oxyhaemoglobin (1.6 x 10(-5) M), but not affected by atropine (10(-7) M),
      propranolol (10(-7) M), phentolamine (10(-7) M), indomethacin (10(-6) M),
      cholecystokinin (CCK, 10(-8) M) and vasoactive intestinal polypeptide (VIP, 10(
      8) M). The relaxation was also abolished by treatment with NG-nitro-L-arginine (L
      NA, 10(-5) M), an NO synthase inhibitor. Nicotine produced a transient
      relaxation, which was abolished by tetrodotoxin, hexamethonium (10(-5) M) and L
      NA, but not affected by atropine and NG-nitro-D-arginine (D-NA, 10(-5) M). The
      addition of K+ elicited a transient relaxation, which was abolished by
      tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L
      arginine (10(-3) M). The presence of neurons containing nicotinamide adenine
      dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the
      sphincter of Oddi. These findings may indicate that TES, nicotine and K+ liberate
      NO from NANC inhibitory nerve which is involved in the relaxation of the dog
      sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic
      nerves under the experimental conditions used.

PMID- 8574911
TI  - Effect of casein and casein hydrolysate on small bowel motility and D-xylose
      absorption in dogs.
AB  - Food administration is followed by the appearance of a small intestinal pattern
      of irregular contractions. Studies on the relationship between intestinal motor
      activity, transit and absorption have yielded contradictory results. Since
      previous studies have shown that casein and casein hydrolysate led to a decrease
      of small intestinal motor activity and transit, the aim was to evaluate the
      effect of these nutrients on small intestinal motility and D-Xylose absorption.
      Studies were performed in five dogs with a duodenal fistula; motility was
      recorded by means of six infused catheters and external transducers. Three test
      solutions with the same osmolality, lactulose, casein and casein hydrolysate,
      were continuously infused through the duodenal cannula. D-Xylose was injected in
      the duodenum and plasma levels determined at regular intervals. Absorption of D
      Xylose was greatest during the administration of casein hydrolysate, the lowest
      levels were seen with lactulose and intermediate levels were obtained with
      casein. The effect of casein hydrolysate on small intestinal motility was
      characterized by a decrease in the frequency of contractions. Propulsive
      contractions were decreased after the infusion of both casein and casein
      hydrolysate. Lactulose infusion was followed by the greatest motor activity of
      both frequency and propulsive contractions. These results suggest that the motor
      patterns observed with casein and casein hydrolysate lead to increased intestinal
      absorption of D-Xylose.

PMID- 8574912
TI  - Influence of age, gender, hormonal status and smoking habits on colonic transit
      time.
AB  - The factors that influence colonic transit time in healthy humans are not yet
      clearly defined. The aim of this study was therefore to determine (a) if there
      are differences in colonic transit time between men and women and (b) if age,
      female hormonal status or smoking habits are associated with alterations in these
      parameters. Colonic transit time was measured in 164 asymptomatic subjects (80
      males, 84 females) by a radio-opaque marker technique with one single plain
      abdominal X-ray. Colonic transit time was significantly shorter in men than in
      women (30 +/- 2 vs. 42 +/- 3 h, P < 0.05). Colonic transit time in non-smoking
      males was significantly shorter compared with smoking males (26 +/- 2 vs. 40 +/-
      5 h, P < 0.05). In females only height and menstrual cycle influenced colonic
      transit times. We conclude that gender and smoking habits should be considered
      when studying colonic transit time in health and disease.

PMID- 8574913
TI  - Oesophageal motility in adult coeliac disease.
AB  - Coeliac sprue is a relatively frequent disease with protean clinical
      manifestations. Recent studies suggest that gastrointestinal motor abnormalities
      may explain some symptoms complained of by such patients. We investigated whether
      coeliac patients have oesophageal motor abnormalities from both a clinical and a
      physiological point of view. Thirty-six consecutive adult sprue subjects (14
      during the florid phase and 22 on gluten-free diet) were studied. A clinical
      questionnaire on gastrointestinal symptoms (with emphasis on those of oesophageal
      origin) was administered. Moreover, 18 patients (13 on free and five on gluten
      free diet) gave their consent for oesophageal manometry and eight subjects for pH
      metry also. Oesophageal clinical symptoms were compared with those of 144 age-
      and sex-matched controls from a general population sample, and manometry with
      that of 34 healthy volunteers. Of coeliac patients 50% complained of dysphagia (P
      < 0.001 vs. controls) and 14% noncardiac chest pain (P = NS vs. controls).
      Manometric examination showed motor abnormalities in 67% of the subjects
      examined, consisting of nutcracker oesophagus, hypotonic lower oesophageal
      sphincter associated with simultaneous contractions, and frequent repetitive (> 3
      peaks) contractions. These abnormalities were equally distributed among free and
      gluten-free diet patients. pH-metry showed only one pathological reflux out of
      eight subjects studied. We conclude that patients with coeliac sprue may display
      abnormal oesophageal motility. This confirms previous studies suggesting that
      gastrointestinal motor abnormalities should probably be added to the clinical
      spectrum of the disease.

PMID- 8574914
TI  - Attention deficit hyperactivity disorder: the scope of the problem.
AB  - Throughout the recent past, the evolution of ADHD as a disability label or
      category has been driven primarily by the development of a series of diagnostic
      manuals by a professional organization (i.e., American Psychiatric Association).
      The result has been a diagnostic category consisting of behaviors that form a
      practical construct of the disability. The evolution of the label and its
      behavioral construct was driven more by the needs of professional manuals than by
      theoretical considerations or empirical research. With the development of
      theoretical models and additional empirical research, however, we appear to be
      gaining a better understanding of the nature of ADHD. New symptom categories have
      more educational and communicative significance, and, importantly, these
      categories appear to have more explanatory value than did previous categories.
      Further investigation of these emerging symptom categories should advance our
      understanding of ADHD and how it can be managed more effectively. As clinicians,
      however, whether we focus on primary symptom categories for clinical/educational
      purposes or emerging symptom categories for their explanatory power, we need to
      continue to gain a better understanding of ADHD and its impact on our students.
      This article has provided a description of the evolution of the ADHD label and
      noted some of the directions that current research appears to be leading. In
      doing so, we hope that we have provided practicing speech-language pathologists
      with a better understanding of the history and scope of this problem.

PMID- 8574915
TI  - Social considerations in the labeling of students as attention deficit
      hyperactivity disordered.

PMID- 8574916
TI  - The responsibilities of speech-language pathologists toward children with ADHD.
AB  - The speech-language pathologist has the skills needed to be an active participant
      in both the diagnostic and intervention phases of the treatment of children with
      ADHD. Many of the behaviors that define ADHD are directly linked to
      communication. Westby and Cutler (1994) assert that "the strong association
      between language disorders and ADHD suggests the possibility of a common
      antecedent to both disorders, perhaps a temperamental or neurological
      characteristic linked to deficits in behavioral regulation" (p. 61). Although the
      speech-language pathologist may not have the security of standardized test scores
      to support his or her diagnosis, behaviors that cannot be tested (e.g.,
      pragmatics and social interactions) may be keys to a child's classroom
      difficulties. As discussed, many of the criteria found in the DSM-IV diagnostic
      criteria for ADHD are characteristics of pragmatic skills. Supported by Barkley's
      (1993) new theory of ADHD which is based on poor response inhibition or inability
      to delay responses, the speech-language pathologist can be an important resource
      to both the teacher and parents by helping them understand the behaviors
      exhibited by an ADHD child. The impulsivity that is so disruptive in the
      classroom is directly linked to the inability to delay responses. It is agreed
      that continued research into the behavioral characteristics associated with ADHD
      as well as their long-term implications for learning is needed. ADHD is a
      multifaceted developmental disorder. There is no known cure for ADHD, and we are
      dependent on early diagnosis and ongoing intervention to reduce its lifelong
      effects. Effective treatment must be multi-modal and involve the coordination of
      a professional team as well as the child's family. It is vital that we help
      children with ADHD develop positive self-esteem, effective social skills, and
      good pragmatic language skills that will eventually have a positive impact on
      their functioning in all aspects of their interactions with their environment. If
      this is accomplished, the effects of ADHD will be minimized. The speech-language
      pathologist needs to take a leadership role in this process.

PMID- 8574917
TI  - ADHD and co-morbidities in infants, toddlers, and preschoolers at risk.

PMID- 8574918
TI  - The metaphysics of ADHD a unifying case scenario.

PMID- 8574919
TI  - Bile formation and hepatic plasma membrane composition in guinea-pigs and rats.
AB  - We compared bile formation, and biliary and liver plasma membrane composition in
      guinea-pigs and rats in an attempt to explain the observation that the bile flow
      rate and the bile acid independent fraction of bile flow (BAIF) in guinea-pigs is
      about five to seven times higher than in rats. Analysis of electrolytes in bile
      showed that bicarbonate was significantly [acid] higher in guinea-pigs while Cl-,
      phosphate and Ca2+ were markedly lower than in rats. High bile independent
      secretion in guinea-pigs was associated with a significantly lower concentration
      of total bile acid, phospholipid and cholesterol than in rats. Bile acid
      distribution studies showed that glycine conjugated chenodeoxycholate and
      ketolithocholate were the main bile acids in guinea-pigs, while taurine
      conjugated cholate and muricholate were the predominant bile acids in rats. Total
      fatty acid analysis of bile indicated that in rats the major fatty acids were
      palmitic acid (C16:0) and linoleic acid (C18:2, n-6). In guinea-pigs, the
      contribution of these fatty acids was lower than in rats and compensated with a
      significantly higher percentage of oleic acid (C18:1, n-9). Concentrations of
      anionic polypeptide fraction (APF), an acidic calcium binding apoprotein closely
      associated with biliary phospholipid and cholesterol secretion was also
      significantly lower in guinea-pigs. Canalicular plasma membrane analysis showed
      that as compared with rats, specific activities of Na+,K+ ATPase, and cholesterol
      and phospholipid content were markedly lower in guinea-pigs.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8574920
TI  - Analysis of zeins' ER retention in Xenopus oocytes.
AB  - Zeins, maize storage proteins, are retained in the endoplasmic reticulum (ER)
      during the intracellular protein targeting process. Hydrophobic interaction has
      been postulated as the driving force of zeins' aggregation and retention in the
      ER. Recently, a class of zein (the 27K zein) has been proposed to facilitate
      zeins' ER retention by anchoring to the ER membrane. This study investigated the
      significance of the two proposed mechanisms toward zeins' ER retention using
      Xenopus oocyte. Following injection of the total or 27K zein mRNA, zein's
      movement within the ER was analyzed based upon the extent of diffusion to the non
      injected oocyte half. This study indicates that the total zeins freely move
      within the lumen of the ER, thus, suggesting that the intermolecular aggregation,
      leading to insolubility and exclusion from the ER lumenal fluid, may not be
      essential for zeins' ER retention. This study also suggests that the 27K zein may
      not facilitate zeins' ER retention by virtue of an anchor to the ER membrane
      based on its free movement in the ER. Free movement of the total and 27K zeins,
      under conditions where zein aggregates should form, necessitates a reevaluation
      of the mechanisms responsible for zein polypeptides' ER retention and protein
      body formation.

PMID- 8574921
TI  - Polymorphic forms of the epithelial mucin, PAS-I (MUC1), in milk of Holstein cows
      (Bos taurus).
AB  - The polymorphic epithelial mucin, PAS-I (also known as MUC1), in individual milk
      samples from 119 Holstein cows was resolved into bands on SDS-gels. Mobility
      indices established for these bands provided evidence of four and possibly five
      polymorphic forms. Sialic acid, a major component of the oligosaccharide portion
      of PAS-I, was removed from the mucin by treatment of milk samples with
      neurominidase. This reduced the mobility of the mucin bands but did not alter
      their mobility relationships within a sample or among samples. Consideration of
      evidence from this and other studies indicates that the four or five polymorphic
      forms correspond to alleles, which are inherited, one each from sire and dam, and
      co-dominantly expressed. It appears that the Holstein population may carry
      several more alleles for PAS-I than do Ayrshire, Jersey or Brown Swiss cattle. In
      addition to these breed differences, some remarkable molecular differences have
      been noted between MUC1 (PAS-I) of human and mouse suggesting that research
      regarding molecular evolution of this mucin could provide another approach to
      understanding relationships among species.

PMID- 8574922
TI  - Primary sequence, tissue specificity and expression of the Na+,K(+)-ATPase alpha
      1 subunit in the European eel (Anguilla anguilla).
AB  - The entire cDNA nucleotide sequence of the Na+,K(+)-ATPase alpha 1 isoform was
      cloned from the gills of the European eel (Anguilla anguilla) by a PCR based
      method. The amino acid sequence translated from the sequence shared 89.4 and
      85.6% homology respectively with previously published Na+,K(+)-ATPase alpha
      subunit sequences from elasmobranch (Torpedo californica) and teleost (Catostomus
      commersoni) fish. The size of Na+,K(+)-ATPase alpha 1 mRNA transcripts in eel
      tissues was demonstrated to be 3.5 kb, except in the ovary where a 3.7 kb
      transcript existed. Na+,K(+)-ATPase alpha 1 mRNA was present at some level in all
      tissues investigated with the exception of cardiac and skeletal muscle where no
      Na+,K(+)-ATPase alpha 1 mRNA was detectable. The level of branchial Na+,K(+)
      ATPase alpha 1 mRNA increased after the adaptation of freshwater eels to normal
      or double concentration seawater.

PMID- 8574923
TI  - Purification and characterization of a multicatalytic proteinase from Atlantic
      salmon (Salmo salar) muscle.
AB  - A high molecular mass alkaline proteinase was purified by DEAE-Sepharose and Mono
      Q chromatography. The mol. wt was estimated to be about 600,000. Under denaturing
      conditions, the enzyme dissociated into a cluster of subunits with mol. wt
      ranging from 25,000 to 30,000. The isoelectric point of the enzyme was about pH
      7.3. The proteinase was able to hydrolyse N-terminal-blocked 4-methyl-7
      coumarylamide substrates for either trypsin- or chymotrypsin-like activity. It
      was also able to hydrolyse haemoglobin and myosin at temperatures of about 60
      degrees C. The activities responded to pH and some chemicals in different ways.
      The trypsin-like activity was clearly inhibited by several serine protease
      inhibitors. These results suggest that the enzyme is multicatalytic, having at
      least two different active sites.

PMID- 8574925
TI  - Restriction endonuclease analysis of mitochondrial DNA of three farm animal
      species: cattle, sheep and goat.
AB  - Five restriction endonucleases (HindIII, BgIII, EcoRI, EcoRV and BamHI) were
      employed to analyse mitochondrial DNA of cattle, sheep and goat. The results
      showed completely different restriction patterns of mtDNA among the three bovid
      species. A total of 11, 16, and 17 restriction fragments in cattle, sheep and
      goat respectively, were detected by the five restriction endonucleases. Average
      total sizes of mtDNA of cattle, sheep and goat were found to be 16.49 +/- 0.18,
      16.30 +/- 0.25 and 16.44 +/- 0.08 kb, respectively. The mtDNA cleavage patterns
      were identical for all seven individuals belonging to two cattle breeds and for
      10 individuals from one sheep breed.

PMID- 8574924
TI  - Cloning of a urochordate cDNA featuring mammalian short consensus repeats (SCR)
      of complement-control protein superfamily.
AB  - Mammalian tumor necrosis factor (TNF)-alpha degenerate polymerase chain reaction
      (PCR) primers were used to amplify a probe from Botryllus schlosseri (colonial
      ascidian) allogeneic rejection-cDNA library. A PCR product (269 bp) was cloned
      and sequenced encoding an open reading frame (ORF) of 89 amino acids (aa). This
      clone, which revealed no similarity to TNF-alpha, but a substantial similarity to
      mammalian proteins featuring short consensus repeats (SCRs) of the complement
      control superfamily, was used to probe the rejection-cDNA library. Two partial
      cDNA clones were isolated and sequenced (Bs.1, 846 bp; Bs.2, 712 bp). The longest
      ORF in clone Bs.1 (which lacks the 5' end of the cDNA) predicts a protein of 251
      aa, which differs from Bs.2 at six nucleotides and four aa. We compare the aa
      similarity (up to 50.5%) of Bs.1 with the SCR-region of mammalian complement
      factor H, apolipoprotein H, selectins, and complement receptors type 1 and type
      2. A somatomedin B-like domain at the C-terminus of Bs.1 deduced protein was also
      recorded. We propose that this mosaic and polymorphic botryllid sequence,
      featuring mammalian-like SCRs, might be an ancestral molecule in the evolution of
      the chordate's complement-control protein superfamily.

PMID- 8574926
TI  - Changes in various plasma lipid components, glucose, and insulin in Spermophilus
      lateralis during hibernation.
AB  - This study evaluated fat mobilization as related to gluconeogenesis in two age
      groups of hibernating golden-mantled ground squirrels (Spermophilus lateralis).
      Our experimental group consisted of a total of 16 male and 15 female squirrels.
      Plasma samples were collected from selected animals being killed weekly from
      January to March, and the concentration of triglycerides, glycerol (GY), free
      fatty acids (FFA), total cholesterol, lipase activity, glucose, and insulin, were
      determined by biochemical assays and radioimmunoassay. Our results showed a mean
      FFA/GY ratio of five, which was higher than the predicted value of three,
      suggesting a significant depletion of GY and an enhanced rate of gluconeogenesis
      via GY to maintain glucose homeostasis in the hibernating animals. The factor of
      age did not significantly affect plasma lipid components. However, in the male
      group, plasma glucose levels were significantly higher for adults than for
      juveniles. Overall, females had significantly higher plasma glucose levels than
      males (150 +/- 11 vs. 110 +/- 8 mg%, P < 0.05). In the adult group, a gender
      influence was also seen on plasma insulin levels, with females' being higher than
      males' (66 +/- 13 vs. 25 +/- 3 microIU/ml, P < 0.01). We suggest that during
      hibernation, female squirrels may have a higher rate of lipolysis and
      gluconeogenesis along with a lower glucose utilization than their male
      counterparts. Additionally, adult females may exhibit a higher peripheral insulin
      resistance during hibernation than adult males, a possibility which merits
      further study.

PMID- 8574927
TI  - Age and sex dependence of the effects of an aqueous extract of Physalis alkekengi
      fruits on rat hepatic glucose 6-P dehydrogenase activity.
AB  - Intraperitoneal injections of an aqueous extract of winter cherry fruits
      (Physalis alkekengi) to new-born, weanling and adult female rats and to weanling
      and adult male rats had no effect on body weight, liver weight and liver cytosol
      protein content. The specific activities of hepatic glucose 6-P dehydrogenase (an
      estrogen induced protein) in rats of different age and sex groups in terms of
      mU/mg protein were: treated new-born females, 15.9 +/- 0.5; control, 29.1 +/-
      0.6; treated weanling females, 14.9 +/- 0.3; control, 24.8 +/- 0.7; treated adult
      females, 25.7 +/- 0.5; control, 26.1 +/- 0.5; treated weanling males, 7.9 +/-
      0.2; control, 7.9 +/- 0.1; treated adult males, 9.6 +/- 0.4; and control, 9.7 +/-
      0.3. Treatment of new-born and weanling female rats with the extract resulted in
      40-45% reduction in hepatic G6PD activity. However, treatment of adult females,
      and weanling and adult males produced no significant change in the activity of
      this enzyme. The data are discussed both in terms of the increase in the capacity
      of rodent liver to metabolize steroidal compounds with age and the presence of
      low levels of circulating estradiol necessary for enzyme induction in male rats.

PMID- 8574928
TI  - [In vitro antibacterial activity of meropenem, a new carbapenem: European data].
AB  - Meropenem is a new DHP-I stable carbapenem with a very promising microbiological,
      pharmacokinetic and clinical profile. The antibacterial activity of this new
      agent has been assessed in vitro against 8741 aerobic and 854 anaerobic strains
      reflecting current incidence and epidemiology in Italy, France, Germany, Spain,
      Switzerland and United Kingdom. Comparator agents were imipenem, ceftriaxone,
      vancomycin, ciprofloxacin gentamicin and amikacin. The results of this study show
      that meropenem has a spectrum of antibacterial activity which embraces the vast
      majority of clinically significant Gram-positive and Gram-negative aerobes and
      anaerobes. This is due in part to excellent stability to chromosomal or plasmid
      mediated beta-lactamases including those which hydrolyse current cephalosporins.
      Data from the Italian study identified meropenem as the most potent agent against
      all Enterobacteriaceae, with the exception of Proteus species with were most
      susceptible to ciprofloxacin. Moreover, meropenem was 10 times more active than
      the other drugs against Haemophilus and Neisseria and was active against all the
      anaerobic strains. Conversely, staphylococci and enterococci were more
      susceptible to imipenem. Overall, these European data showed that meropenem was
      the most powerful drug against Enterobacteriaceae and it also was the most
      effective drug tested against the Italian and French Pseudomonas aeruginosa
      strains. Meropenem was less effective than imipenem or vancomycin against
      Enterococcus stains but had similar activity to imipen against anaerobes. Based
      on this microbiological profile, the use of meropenem is appropriate in the
      empirical treatment of serious infections, including those caused by multiple
      pathogens.

PMID- 8574929
TI  - [Preclinical evaluation of meropenem, a new parenteral carbapenem].
AB  - Meropenem is a new carbapenem antibiotic that is stable to human renal
      dehydropeptidase-I (DHP-I) and exhibits potent bactericidal activity against
      almost all clinically significant aerobic and anaerobic bacteria. Activity is
      achieved through rapid entry into bacteria, resisting hydrolysis by all serine
      based beta-lactamases, both of chromosomal or plasmid origin, and high affinity
      for vital penicillin binding proteins. The antibacterial spectrum of meropenem
      has been investigated extensively in a world-wide programme of studies. The
      results from all of these studies are consistent and identify in vitro
      differences between meropenem and imipenem. Both agents demonstrate high activity
      against Gram-positive aerobes with meropenem slightly less active than imipenem
      but significantly more potent than imipenem against Haemophilus influenza, all
      Enterobacteriaceae and 2-4 fold more active against Pseudomonas aeruginosa and
      most other pseudomonas. The spectrum of carbapenems is superior to that of all
      other beta-lactams. This is achieved, in part, by stability to the chromosomal
      beta-lactamases which hydrolyse ceftazidime, cefotaxime and ceftriaxone and
      against which newer agents like cefpirome and cefepime are not fully stable.
      Meropenem is also stable to the new plasmid-mediated enzymes which are
      responsible for significant elevation of MIC's of all cephalosporins and
      penicillins. When tested against P. Aeruginosa which have become resistant to
      imipenem therapy, these strains remained susceptible to meropenem. The activity
      of meropenem against anaerobes is at least as potent as metronidazole and
      clindamycin. These impressive in vitro data have been the basis for an extensive
      clinical evaluation programme in many indications including infections caused by
      single or multiple pathogens.

PMID- 8574930
TI  - Ultrasound and dual X-ray absorptiometry densitometry in women with hip fracture.
AB  - To assess the usefulness of the measurement of the os calcis by ultrasound, a
      method that probably reflects bone quality as well as density, we have studied 54
      women with hip fracture of the proximal femur and a control group. Ultrasound
      evaluation of the os calcis [broadband ultrasound attenuation (BUA), speed of the
      sound (SOS), and a combined index ("stiffness")], and bone mineral density (BMD)
      determination over the proximal femur by dual X-ray absorptiometry (DXA) were
      performed. Weight, BMD, and ultrasound values in the hip fracture patients were
      significantly lower than controls (P < 0.001). The Z-scores for BUA and stiffness
      were not different than that for femoral neck, Ward's triangle or trochanteric
      BMD (between -1.7 and -1.5). The odds ratios determined by receiver-operating
      characteristics (ROC) analysis were greater at the femoral neck (25.1) and BUA
      (24.4). Intermediate values were found at stiffness (16.9), Ward's triangle
      (12.8), and trochanter (11.1), and lower values were obtained at SOS (4.2). In
      turn, patients with trochanteric hip fractures had a significantly lower femoral
      neck and Ward's triangle BMD, stiffness, and BUA than patients with cervical hip
      fractures. Comparing a subgroup of 30 women with hip fractures without vertebral
      fractures with an age-matched group of 87 women with osteoporotic vertebral
      fractures, both groups were of similar weight and BMD but all ultrasound values
      were significantly lower in the hip fractures compared with vertebral fracture
      patients (P < 0.05 - P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574931
TI  - Influence of degenerative joint disease on spinal bone mineral measurements in
      postmenopausal women.
AB  - We assessed the impact of various forms of spinal degenerative joint disease
      (DJD) on bone mineral density (BMD) measured by quantitative computed tomography
      (QCT) and dual X-ray absorptiometry (DXA) in a group of postmenopausal women.
      Lateral (T4-L4) and AP (L1-L4) spinal radiographs were reviewed for fracture and
      DJD in 209 women (mean age 62.6 +/- 6.7). The severity of DJD findings was graded
      as 0, 1, or 2 on the lumbar films, except for vertebral osteophytes which were
      graded from 0 to 3. Vertebral fractures were defined semiquantitatively as
      approximately 20% reduction in anterior, middle, or posterior vertebral height.
      BMD was measured in all subjects by QCT and DXA, including posteroanterior DXA
      (PA-DXA), lateral DXA (L-DXA) and midlateral DXA (mL-DXA). When BMD was measured
      by QCT and mL-DXA in the 168 women without fractures, no significant differences
      were found between women with and those without DJD. However, BMD by PA-DXA was
      significantly higher in women with DJD changes, particularly when osteophytes
      were present at the vertebral bodies or facet joints. BMD by L-DXA was less
      affected by DJD. For this measurement a significant increase in BMD was only
      noted in subjects with vertebral osteophytes. Multivariate analysis of variance
      (MANOVA) showed that BMD by QCT and mL-DXA was not affected by DJD. In contrast,
      for all women, BMD by PA- and L-DXA was affected more by DJD than by fracture
      status. Chi-square testing demonstrated no significant relationships between
      vertebral fractures and any of the DJD changes. We conclude that QCT and mL-DXA
      are superior to PA-DXA and L-DXA in detecting bone loss in patients with DJD.
      Thus, for these patients, BMD assessment by QCT or mL-DXA may be advisable.

PMID- 8574932
TI  - Acute biochemical variations induced by two different calcium salts in healthy
      perimenopausal women.
AB  - Despite the potential utility of calcium supplementation and the availability of
      many calcium supplements in the market, there are few data concerning the
      absorbability of different calcium salts in different conditions. We have
      compared the acute metabolic responses following oral administration of calcium
      citrate (CC) or calcium gluconolactate and carbonate (CGC) given to 20 healthy
      perimenopausal women (aged 48-55 years). Ten women received two effervescent
      tablets of CC (each containing 500 mg of calcium) and 10 women received two
      effervescent tablets of CGC (each containing 500 mg of calcium). Before and on an
      hourly basis for 6 hours, serum total and ionized calcium, phosphate, and
      immunoreactive parathyroid hormone (iPTH) were measured. Urinary calcium and
      creatinine were also measured. Both calcium salts induced significant increase in
      serum total and ionized calcium and in urinary calcium excretion; they also
      significantly reduced circulating levels of iPTH. The analysis of ionized calcium
      and iPTH response curves to CC and CGC administration revealed a significantly
      greater bioavailability of CC compared with CGC. Our data suggest that CC could
      be prefered to CGC for its characteristics of absorbability and bioavailability.

PMID- 8574934
TI  - Growth plate pathology in feline mucopolysaccharidosis VI.
AB  - The mucopolysaccharidoses (MPS) are a family of lysosomal storage diseases that
      result from the accumulation of partially catabolized glycosaminoglycans (GAGs)
      within lysosomes. A characteristic of most affected individuals is radiographic
      evidence of symmetrical epiphyseal dysplasia, with short stature and degenerative
      joint disease. Although there is evidence of epiphyseal dysfunction, little is
      known of the changes that occur at the morphological level. The growth plate of
      the femoral head was studied by light and electron microscopy in five cats with
      MPS VI (Maroteaux-Lamy syndrome, arylsulfatase B deficiency) and 12 normal cats.
      Compared with the normals, the MPS VI cat growth plates exhibited poorly
      organized proliferative zones, an almost total loss of column formation in the
      hypertrophic zone, an uneven chondro-osseous junction, a disorganized calcifying
      cartilage zone, and abnormal or reduced numbers of osteoclasts. By electron
      microscopy, the cytoplasm of affected cat chondrocytes was filled with membrane
      bound vacuoles. Together these findings indicate that the MPS diseases cause
      major changes in growth plate structure and function.

PMID- 8574933
TI  - Morphological alterations in dental and periodontal tissues in murine
      mucopolysaccharidosis type VII.
AB  - Mucopolysaccharidoses (MPSs) in humans are frequently associated with tooth and
      periodontal aberrations. Although the cause is known, namely, enzyme deficiency,
      the pathophysiology of these alterations is not well defined. A murine MPS VII
      (beta-glucuronidase deficiency) model has earlier been identified with
      morphological, genetic, and biochemical characteristics that closely mimic those
      of human MPS VII. The present investigation describes the histopathological
      alterations in dental and periodontal tissues from such mutant mice. Homozygous
      animals were identified by external phenotypical features and as being beta
      glucuronidase deficient by a fluorometric assay of liver samples. In the incisor
      and the periodontium, abnormalities were evident in both cells and the
      extracellular matrices. Mesenchyme-derived cells were more aberrant than
      epithelial cells. Moreover, undifferentiated cells appeared unaffected, whereas
      actively synthesizing and resorbing cells were distended by virtually empty or
      granular material-containing vacuoles, the content presumably being
      glycosaminoglycans. The cells most affected were those in which macromolecular
      turnover is normally the highest, namely, odontoblasts, postsecretory
      ameloblasts, and periodontal ligament fibroblasts. Extracellularly, predentin
      displayed abnormal collagen fibrils, whereas mineralization defects occurred in
      both dentin and enamel. This murine model of MPS VII provides a good tool for
      understanding the pathophysiology of this disease in bone, periodontium, and
      teeth.

PMID- 8574935
TI  - Bone mineral density in feline mucopolysaccharidosis VI measured using dual
      energy X-ray absorptiometry.
AB  - Dual-energy X-ray absorptiometry (DXA) was used to determine the in vivo bone
      mineral density (BMD) and bone mineral content (BMC) of lumbar vertebrae in six
      cats affected with the inherited lysosomal storage disease mucopolysaccharidosis
      VI (MPS VI). DXA was also performed on MPS cats that had a bone marrow transplant
      (BMT) and total body irradiation (TBI) (MPS + BMT; n = 7), normal cats that had a
      bone marrow transplant, and TBI (control + BMT; n = 8) and normal cats (control;
      n = 14). Following euthanasia, one of the lumbar vertebrae that had been scanned
      (L5) was harvested and bone volume (BV/TV%) was determined by histomorphometry.
      The in vivo BMD and BMD measurements were compared with the BV/TV%. There was a
      greater BMD and BMC in the MPS + BMT cats compared with the MPS cats but the
      difference was not statistically significant. However, there was a greater BV/TV%
      in the MPS + BMT cats compared with the MPS cats and the difference was
      significant (P = 0.0152). Correlation between the noninvasive in vivo DXA
      measurements of BMD and BMC and the BV/TV% was significant (r2 = 0.767, P <
      0.0001; r2 = 0.504, P < 0.0001). Noninvasive in vivo DXA was a rapid and precise
      method for measuring the lumbar BMD and BMC in cats and it correlated well with
      histomorphometric determination of bone mass. Further, the response of inherited
      storage diseases such as MPS VI to therapy, such as BMT, could be monitored in a
      longitudinal fashion using DXA.

PMID- 8574936
TI  - Expression of parathyroid hormone-related protein in rat articular cartilage.
AB  - Expression and localization of parathyroid hormone-related protein (PTHrP) in rat
      articular cartilage during fetal and postnatal periods were investigated by
      immunohistochemistry and in situ hybridization. PHTrP displayed distinct
      distribution and intensity of staining at different ages. In fetal (18-day-old)
      and young (3-week-old) rats, articular chondrocytes expressed abundant PTHrP
      throughout the entire thickness of cartilage. In contrast, in 60-week-old rats,
      PTHrP was expressed in a few articular chondrocytes of superficial and middle
      layers. Regulation of PTHrP and PTH/PTHrP receptor mRNA was also studied in
      cultured rat articular chondrocytes. Northern blot analysis revealed that both
      transforming growth factor-beta (TGF-beta), an important stimulator for
      chondrocyte proliferation and differentiation, and 10% fetal bovine serum (FBS)
      stimulated the expression of PTHrP mRNA with down-regulation of its receptor
      mRNA. In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA) down-regulated the
      expression of receptor without changes of PTHrP mRNA level. These results suggest
      that the changes in abundance and localization of PTHrP and its receptor may be
      directly involved in the cell growth and differentiation of articular cartilage.

PMID- 8574937
TI  - Correlation of bone mineral density and femoral neck hardness in bovine and human
      samples.
AB  - Bone mineral density (BMD) is a predictor of fracture risk. The purpose of this
      study was to determine whether a correlation exists between femoral neck BMD and
      an indicator of mechanical bone strength in human and bovine samples. Human
      proximal femurs were obtained from seven men and two women undergoing total hip
      arthroplasty (THA), mean age 60.3 years. Preoperative BMD measurements of the
      femoral neck were obtained (Lunar DPX). A 3 cm2 area of interest on each excised
      femoral neck corresponding to the preoperative BMD measurement site was carefully
      marked and BMD was remeasured postoperatively. Ten excised bovine femoral necks
      were also measured for BMD. A bicortical core, each cortex 2.8 cm2 in area,
      containing the center of the area of interest was removed from the human and
      bovine femoral necks, cut into multiple 7-mm thick, multiple cross-sectional
      discs, and measured for hardness by indent depth (Rockwell International Hardness
      Tester, Wilson Mechanical Instruments, New York, NY). In vivo human femoral neck
      BMD measurements correlated with in vitro BMD measurements (r = 0.99). BMD
      measurements of human femoral necks were significantly lower than BMD
      measurements of bovine femoral necks (P < 0.05). Inverse relationships were found
      between in vivo and in vitro human BMD measurements and indent depth (r = -0.58
      and -0.59, respectively). Bovine BMD measurements and indent depth were also
      inversely related (r = -0.64).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574938
TI  - An age-related decrease in the concentration of insulin-like growth factor
      binding protein-5 in human cortical bone.
AB  - The skeletal contents of insulin-like growth factor-2 (IGF-II), insulin-like
      growth factor binding protein-5 (IGFBP-5), and insulin-like growth factor binding
      protein-3 (IGFBP-3) were determined in duplicate samples of human femoral
      cortical bone obtained from 64 subjects (44 males and 20 females) between the
      ages of 20 and 64 years. The results of these quantitative measurements revealed
      an age-related decrease in the femoral cortical content of IGFBP-5 (r = -0.272, P
      = 0.031) in the total population. Although the femoral cortical content of IGF-II
      did not show a similar decrease with age, it could be correlated to the femoral
      cortical content of IGFBP-5 (r = 0.442, P < 0.001). In contrast, the femoral
      cortical content of IGFBP-3 did not decrease with age and could not be correlated
      to the femoral cortical contents of either IGFBP-5 or IGF-II. Comparisons of
      these results with previous measurements of insulin-like growth factor-1 (IGF-I)
      and transforming growth factor-beta (TGF-beta), in extracts of the same bones,
      showed significant cross-correlations between the femoral cortical contents of
      each of these growth factors and the femoral cortical contents of IGFBP-5 (r =
      0.625 for IGF-I versus IGFBP-5, r = 0.554 for TGF-beta versus IGFBP-5, P < 0.001
      for each) but not IGFBP-3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574939
TI  - Immunohistochemical identification of proteoglycan form of macrophage colony
      stimulating factor on bone surface.
AB  - Several studies using op/op mice have shown that macrophage colony-stimulating
      factor (M-CSF) was necessary for osteoclast formation in vivo. Previously we
      reported that osteoblastic cells produced two molecular forms of M-CSF; one is an
      85-kDa M-CSF, and the other is a proteoglycan form of M-CSF (PG-M-CSF) which has
      a binding affinity for bone-derived collagens and is extractable from human bone.
      In this study, we performed immunostaining of human bone using a newly
      established anti-PG-M-CSF antibody, and showed positive staining PG-M-CSF,
      probably produced by bone lining cells, on the bone surface. This observation
      suggests that the bone surface is suitable for osteoclast formation because of
      the presence of PG-M-CSF.

PMID- 8574940
TI  - Zinc decrease and bone metabolism in the femoral-metaphyseal tissues of rats with
      skeletal unloading.
AB  - Whether the decrease of zinc content in the femoral-metaphyseal tissues of rats
      with skeletal unloading is involved in the alteration of bone metabolism was
      investigated. Skeletal unloading was designed using the model of hindlimb
      suspension in rats. Animals were fed for 4 days with the unloading. The
      metaphyseal zinc content were significantly decreased by the unloading. Zinc
      accumulation in the metaphyseal tissues by a single oral administration of zinc
      sulfate (20 mg Zn/100 g body weight) was partially depressed by the unloading,
      although serum zinc concentration was higher than that in normal rats, suggesting
      an impaired movement of zinc from serum into bone tissues by the unloading.
      Skeletal unloading caused a significant decrease of alkaline phosphatase activity
      and deoxyribonucleic acid (DNA) content in the metaphyseal tissues. These
      decreases were completely restored by addition of zinc sulfate (10(-4) M) or beta
      alanyl-L-histidinato zinc (AHZ; 10(-5) M) in a culture medium with the
      metaphyseal tissues in vitro. The effects of zinc compounds were abolished by the
      presence of cycloheximide (10(-8) M), suggesting that the zinc effect is based on
      a newly synthesized protein. Dipicolinate (10(-4) and 10(-5) M), a potent zinc
      chelating agent, caused an appreciable decrease of zinc content and alkaline
      phosphatase activity in the metaphyseal tissues. This decrease was restored by
      zinc supplement. The present results suggest that the skeletal unloading-induced
      decrease of zinc content in the femoral-metaphyseal tissues plays a role in the
      deterioration of bone metabolism in the unloaded rats.

PMID- 8574941
TI  - Ineffectiveness of calcitonin on a local-disuse osteoporosis in the sheep: a
      histomorphometric study.
AB  - Local immobilization is a good model for studying disuse-induced bone loss and to
      appreciate the effects of drugs, especially preventive action of antiresorptive
      therapy. In fact, increased osteoclastic activity is the main point of such a
      bone loss. The effect of salmon calcitonin was investigated on immobilization
      induced osteoporosis in the sheep. Twenty-four nonovariectomized, adult, female,
      Welsh mountain sheep were submitted, by an external fixator procedure, to hock
      joint immobilization from the tibia to the the metatarsus for 12 weeks. The sheep
      were randomized into two groups receiving either an injection of placebo or
      salmon calcitonin (100 IU) three times per week, for 12 weeks. Histomorphometric
      analysis was performed on pre- and posttherapeutic transiliac bone biopsies, and
      on immobilized (left) and nonimmobilized calcanei removed after sacrifice.
      Results showed a 29% significant decrease of cancellous bone volume in the
      placebo group due to a significant reduced trabecular thickness when we compared
      immobilized versus nonimmobilized calcaneus. This structural adaptation appeared
      to be the consequence of an overall increased bone turnover. In the calcitonin
      group, same changes were observed, with a 23% reduction of bone mass in the
      immobilized calcaneus. By comparing calcitonin with placebo groups in both left
      and right calcanei, no difference was found. On the other hand, a significant
      increase of mineralization parameters in the iliac crest was only observed in the
      calcitonin group. In conclusion, salmon calcitonin, at a dose of 100 IU/day three
      times a week, was ineffective in preventing local disuse osteoporosis in this
      sheep model.

PMID- 8574943
TI  - Extracellular processing of dentin matrix protein in the mineralizing odontoblast
      culture.
AB  - Odontoblasts that we prepared from bovine incisors produced a dentin-specific
      protein, phosphophoryn, and accumulated it in mineralized nodules. The time
      course of mineralization was detected by measuring osteocalcin and mineral in the
      nodules. The sequence of developmental expression of proteins in this
      mineralizing dentin cell culture is very similar to that in bone cells,
      suggesting a common mechanism for matrix mineralization in bone and dentin.
      Casein kinase II, which phosphorylates bone phosphoproteins and dentin
      phosphorylates bone phosphoproteins and dentin phosphophoryn, also emerges
      coinciding with the initiation of mineralization. Furthermore, we have detected
      extracellular phosphorylation by casein kinase II of a dentin protein of M(r)
      60,000, which we recovered from the phosphophoryn fraction in CaCl2 precipitate.

PMID- 8574942
TI  - Effects of deferoximine on chondrocyte alkaline phosphatase activity: proxidant
      role of deferoximine in thalassemia.
AB  - The homozygous form of beta-thalassemia, the most common single gene disorder, is
      treated by red cell transfusion therapy. Following transfusion, the chelator,
      deferoximine, is administered to patients to remove excess iron. However, when
      this drug is given to young children, metaphyseal dysplasia and abnormalities of
      linear growth are frequently observed. To explore the notion that deferoximine
      interferes with endochondral growth by chelating zinc, we examined the effect of
      the drug on chondrocytes maintained in long-term culture. We found that
      deferoximine caused a dose-dependent inhibition of a wide range of functions
      including cell proliferation, protein synthesis (and possibly under-hydroxylation
      of type X collagen), and mineral deposition. Directly relevant to the
      mineralization process was the observation that the drug dramatically lowered the
      activity of alkaline phosphatase, a zinc-requiring enzyme. To test the hypothesis
      that enzyme inhibition was due to chelation of zinc by deferoximine, the cell
      culture medium was supplemented with excess zinc. However, this treatment did not
      overcome the deferoximine-dependent change in enzyme activity. We next examined
      the possibility that deferoximine, in the presence of ascorbate, could form a
      free radical system that would serve to inactivate the enzyme. Using alkaline
      phosphatase extracted from chick cartilage, we noted that the activity of the
      phosphatase was markedly reduced in the presence of deferoximine and ascorbate.
      These effects were consistant with the notion that deferoximine and ascorbate can
      act as a prooxidant couple. This conclusion was confirmed when we measured the
      oxidative activities of the system using nitrobule tetrazolium and cytochrome c.
      Indeed, we noted that deferoximine markedly activates the autocatalytic oxidation
      of ascorbate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8574945
TI  - Let's talk about dying.

PMID- 8574944
TI  - Inhibitory effects of 9-cis and all-trans retinoic acid on 1,25(OH)2 vitamin D3
      induced bone resorption.
AB  - The effects of retinoic acid (RA), and calcitriol are mediated by specific
      nuclear receptors (RARs and VDR, respectively). Induction of RAR and VDR
      responsive elements in target genes requires a cofactor, the retinoid-X-receptor
      (RXR), with its ligand 9-cis RA. We have previously demonstrated the expression
      of RARs and RXRs in osteoblasts, and herein investigated the effects of the
      retinoids all-trans RA and 9-cis RA alone and combined with calcitriol on bone
      resorption in vitro, measured by 45Ca-release from prelabeled neonatal mouse
      calvarial bones. All-trans RA and 9-cis RA were powerful stimulators of bone
      resorption and essentially equipotent. At threshold concentrations (1 nM) both 9
      cis RA and at-RA markedly inhibited the resorption induced by calcitriol (1 pM).
      The findings are compatible with a physiological role for retinoids in bone
      metabolism.

PMID- 8574946
TI  - Leptin and nerve growth factor regulate adipose tissue.

PMID- 8574947
TI  - The real Kaposi's sarcoma.

PMID- 8574950
TI  - AIDS physicians find support in the trenches.

PMID- 8574949
TI  - Thalidomide neuropathy.

PMID- 8574948
TI  - . . . and surreal antisense?

PMID- 8574951
TI  - Human gene therapy--an immature genie, but certainly out of the bottle.

PMID- 8574952
TI  - The clinical significance of an autoimmune response against glutamic acid
      decarboxylase.
AB  - Glutamic acid decarboxylase is attracting much interest because of its putative
      involvement in two clinical disorders: stiffman syndrome and insulin-dependent
      diabetes. Here we discuss the clinical significance of an autoimmune response
      against GAD and consider how such information may help identify the disease
      mechanisms of these disorders.

PMID- 8574953
TI  - A "complement-ary" AIDS vaccine.
AB  - The human immunodeficiency virus uses the human complement system to its
      advantage. Is it possible to turn the tables with a vaccine?

PMID- 8574954
TI  - Are we any closer to genetic testing for common malignancies?

PMID- 8574955
TI  - Of telomeres and tumors.
AB  - The enzyme, telomerase, may be switched on in tumor cells. Inhibitors of this
      enzyme might constitute a new class of anti-cancer drugs.

PMID- 8574956
TI  - New detachable coils for treating cerebral aneurysms.

PMID- 8574957
TI  - Preemptive therapy for genetic disease.

PMID- 8574958
TI  - Liver transplants contribute to their own success.

PMID- 8574959
TI  - A lesson from the HIV patient: the immune response is still the bane (or promise)
      of gene therapy.

PMID- 8574960
TI  - Tumor angiogenesis and tissue factor.

PMID- 8574961
TI  - Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer
      patients.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant
      disorder characterized by the early onset of colorectal cancer and linked to
      germline defects in at least four mismatch repair genes. Although much has been
      learned about the molecular pathogenesis of this disease, questions related to
      effective presymptomatic diagnosis are largely unanswered because of its genetic
      complexity. In this study, we evaluated tumors from 74 HNPCC kindreds for genomic
      instability characteristic of a mismatch repair deficiency and found such
      instability in 92% of the kindreds. The entire coding regions of the five known
      human mismatch repair genes were evaluated in 48 kindreds with instability, and
      mutations were identified in 70%. This study demonstrates that a combination of
      techniques can be used to genetically diagnose tumor susceptibility in the
      majority of HNPCC kindreds and lays the foundation for genetic testing of this
      relatively common disease.

PMID- 8574962
TI  - The role of interleukin-15 in T-cell migration and activation in rheumatoid
      arthritis.
AB  - Interleukin 15 (IL-15) is a novel cytokine with interleukin-2-like activity. It
      is also a potent T-lymphocyte chemoattractant. Rheumatoid arthritis (RA) is a
      chronic inflammatory disease characterized by the presence of activated T
      lymphocytes, macrophages and synoviocytes in the synovial membrane. The
      mechanisms of T-cell activation in RA are currently unclear. We report the
      presence of high concentrations of IL-15 in rheumatoid arthritis (RA) synovial
      fluid and have demonstrated its expression in the synovial membrane lining layer
      by immunohistochemistry. RA synovial fluids were found to contain chemotactic
      activity, which was attributable in part to the presence of IL-15. Moreover, in a
      murine model, injection of recombinant IL-15 was found to induce a local tissue
      inflammatory infiltrate consisting predominantly of T lymphocytes. Synovial fluid
      T lymphocytes proliferate in response to IL-15, demonstrating that continued
      responsiveness to IL-15 is a feature of T cells after entry into the synovial
      compartment. These data suggest that IL-15 can recruit and activate T lymphocytes
      in the synovial membrane, thereby contributing to RA pathogenesis.

PMID- 8574964
TI  - Evidence that hematopoiesis may be a stochastic process in vivo.
AB  - To study the behavior of hematopoietic stem cells in vivo, hematopoiesis was
      simulated by assuming that all stem cell decisions (that is, replication,
      apoptosis, initiation of a differentiation/maturation program) were determined by
      chance. Predicted outcomes from simulated experiments were compared with data
      obtained in autologous marrow transplantation studies of glucose 6-phosphate
      dehydrogenase (G6PD) heterozygous female Safari cats. With this approach, we
      prove that stochastic differentiation can result in the wide spectrum of discrete
      outcomes observed in vivo, and that clonal dominance can occur by chance. As the
      analyses also suggest that the frequency of feline hematopoietic stem cells is
      only 6 per 10(7) nucleated marrow cells, and that sem cells do not replicate on
      average more frequently than once every three weeks, these large-animal data
      challenge clinical strategies for marrow transplantation and gene therapy.

PMID- 8574963
TI  - Selective depletion of myelin-reactive T cells with the anti-OX-40 antibody
      ameliorates autoimmune encephalomyelitis.
AB  - The OX-40 protein was selectively upregulated on encephalitogenic myelin basic
      protein (MBP)-specific T cells at the site of inflammation during the onset of
      experimental autoimmune encephalomyelitis (EAE). An OX-40 immunotoxin was used to
      target and eliminate MBP-specific T cells within the central nervous system
      without affecting peripheral T cells. When injected in vivo, the OX-40
      immunotoxin bound exclusively to myelin-reactive T cells isolated from the CNS,
      which resulted in amelioration of EAE. Expression of the human OX-40 antigen was
      also found in peripheral blood of patients with acute graft-versus-host disease
      and the synovia of patients with rheumatoid arthritis during active disease. The
      unique expression of the OX-40 molecule may provide a novel therapeutic strategy
      for eliminating autoreactive CD4+T cells that does not require prior knowledge of
      the pathogenic autoantigen.

PMID- 8574965
TI  - Presence of hematopoietic stem cells in the adult liver.
AB  - Recently, cases have been reported in which a mixed chimeric state of blood cells
      is established after liver transplantation. Because the established chimerism may
      have aided in the induction of donor-specific tolerance, the mechanism
      responsible for this chimerism is of clinical importance. To establish this, we
      examined cells in adult mouse liver and identified the presence of c-kit+ Sca-1+
      Lin(lo/-) cells. These cells were capable of forming in vivo as well as in vitro
      colonies. Furthermore, the cells could reconstitute bone marrow of lethally
      irradiated recipient mice for at least 12 months. These data obtained from the
      mouse study strongly suggest that hematopoietic stem cells residing in the donor
      liver are responsible for mixed chimerism and maintenance of tolerance after
      liver transplantation.

PMID- 8574966
TI  - Novel fibrillar structure confers adhesive property to malaria-infected
      erythrocytes.
AB  - Infections with the malaria parasite Plasmodium falciparum are characterized by
      sequestration of erythrocytes infected by mature forms of the parasite.
      Sequestration seems critical for the survival of the parasite, but may lead to
      excessive binding in the microvasculature and death of the human host. We report
      here that a novel electrondense fibrillar structure, containing immunoglobulins M
      or M and G, is found at the surface of infected erythrocytes that adhere to host
      cells. In cases of cerebral malaria, fibrillar strands are also seen in the
      microvasculature at autopsy. Our findings may explain the adhesive mechanism by
      which malaria-infected erythrocytes cause the vascular obstruction seen in
      complicated malaria infections.

PMID- 8574967
TI  - In situ detection of tissue factor in vascular endothelial cells: correlation
      with the malignant phenotype of human breast disease.
AB  - Expression of tissue factor (TF) in the endothelium has been observed only rarely
      in human disease and has been thought to be elaborated on the surface of vascular
      endothelial cells (VECs) in vitro as an artifact of tissue culture. Using
      monoclonal antibodies and a novel probe for functional TF, we have localized TF
      to the VECs (and tumor cells) within the tumors of seven patients with invasive
      breast cancer but not in the VECs (or tumor cells) of benign tumors from ten
      patients with fibrocystic disease of the breast. The potent procoagulant TF was
      shown to be a marker of the initiation of angiogenesis in human breast cancer.
      Further evidence that the TF was the demonstration of a similar distribution of
      cross-linked fibrin only in the VECs of the malignant tumors. We interpret these
      data as further support for the concept that tumor cells can activate nearby VECs
      and regulate blood vessel growth in vivo. Large clinical pathologic studies will
      be necessary to determine whether TF is a useful marker for the "switch" to the
      angiogenic phenotype" in human breast disease and/or correlates with the
      thromboembolic complications of breast cancer.

PMID- 8574968
TI  - T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes
      in HIV-infected patients.
AB  - The introduction and expression of genes in somatic cells is an innovative
      therapy for correcting genetic deficiency diseases and augmenting immune
      function. A potential obstacle to gene therapy is the elimination of such gene
      modified cells by an immune response to novel protein products of the introduced
      genes. We are conducting an immunotherapy trial in which individuals seropositive
      for human immunodeficiency virus (HIV) receive CD8+ HIV-specific cytotoxic T
      cells modified by retroviral transduction to express a gene permitting positive
      and negative selection. However, five of six subjects developed cytotoxic T
      lymphocyte responses specific for the novel protein and eliminated the transduced
      cytotoxic T cells. The rejection of genetically modified cells by these
      immunocompromised hosts suggests that strategies to render gene-modified cells
      less susceptible to host immune surveillance will be required for successful gene
      therapy of immunocompetent hosts.

PMID- 8574969
TI  - Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and
      localization to intracellular membranes in mammalian cells.
AB  - Mutations in two recently identified genes appear to cause the majority of early
      onset familial Alzheimer's disease (FAD). These two novel genes, presenilin 1
      (PS1) and presenilin 2 (PS2) are members of an evolutionarily conserved gene
      family. The normal biological role(s) of the presenilins and the mechanism(s) by
      which the FAD-associated mutations exert their effect remain unknown. Employing
      in situ hybridization, we demonstrate that the expression patterns of PS1 and PS2
      in the brain are extremely similar to each other and that messages for both are
      primarily detectable in neuronal populations. Immunochemical analyses indicate
      that PS1 and PS2 are similar in size and localized to similar intracellular
      compartments (endoplasmic reticulum and Golgi complex). FAD-associated mutations
      in PS1 and PS2 do not significantly modify either their migration patterns on SDS
      polyacrylamide gel electrophoresis or their overall subcellular localization,
      although subtle differences in perinuclear staining were noted for mutant PS1.

PMID- 8574970
TI  - Bovine beta-lactoglobulin modified by 3-hydroxyphthalic anhydride blocks the CD4
      cell receptor for HIV.
AB  - Sexual transmission is the most frequent (86%) route of adult HIV-1 transmission
      worldwide. In the absence of a prophylactic anti-HIV vaccine, other methods of
      preventing infection should be implemented. Virucidal spermicides have been
      considered for this purpose, but their application is contraindicated by adverse
      effects. Anti-HIV drugs or virus-neutralizing monoclonal antibodies are
      expensive, suggesting that their wide use in topical chemoprophylaxis is
      unlikely. This emphasizes the importance of developing other methods for
      preventing HIV transmission. The target cells for sexual and mucosal HIV
      transmission include T lymphocytes, monocytes/macrophages and dendritic cells.
      Therefore, compounds blocking HIV-CD4 binding are expected to inhibit virus
      transmission. In exploring the possibility that chemical modification of food
      proteins might lead to compounds with anti-HIV-1 activity, we found that bovine
      beta-lactoglobulin (beta-LG) modified by 3-hydroxyphthalic anhydride (3HP-beta
      LG) (1) blocked at nanomolar concentrations the binding to CD4 of human (HIV) and
      simian (SIV) immunodeficiency virus surface glycoproteins and monoclonal
      antibodies specific for the HIV binding site on CD4 and (2) inhibited infection
      by HIV-1, including primary virus isolates, by HIV-2 and by SIV. The inexpensive
      and widely available source (whey) for production of 3HP-beta-LG suggests its
      potential application (nonparenteral) for diminishing the frequency of HIV
      transmission.

PMID- 8574971
TI  - Detection of dental decay and its extent using a.c. impedance spectroscopy.
AB  - Dental caries (decay), the most prevalent of diseases, represents a health
      problem of immense proportions. It principally affects posterior (back) teeth on
      occlusal (biting) and approximal (adjacent contacting) surfaces. Caries starts as
      a subsurface demineralization of enamel, may progress to the underlying dentine
      and, eventually, to cavitation of the surface. Accurate diagnosis before
      cavitation would permit targeted preventive treatment, thereby significantly
      improving dental health and reducing the need for expensive drilling and filling.
      Inaccessibility of caries initiation sites and recent changes in lesion
      morphology contribute to the relatively poor accuracy of conventional diagnostic
      methods. Among alternative techniques, measurements of electrical resistance have
      shown the most promise. Here we describe a new experimental technique that
      demonstrates an outstanding 100% correlation between a.c. impedance measurements
      of whole teeth and the actual extent of approximal caries in vitro. Only
      relatively minor modifications should be required to transfer the technique to in
      vivo applications.

PMID- 8574972
TI  - Retinoic acid normalizes the increased gene transcription rate of TGF-alpha and
      EGFR in head and neck cancer cell lines.
AB  - Retinoic acid (RA) has been shown to be effective in eradicating premalignant
      lesions and preventing second primary malignancies in patients cured of squamous
      cell carcinoma of the head and neck (SCCHN) in clinical trials. The basis for
      this effect is unclear. We have previously demonstrated that messenger RNA from
      tumor growth factor-alpha (TGF-alpha) and its receptor, the epidermal growth
      factor (EGFR), is unregulated in tumors and histologically normal mucosal samples
      from patients with SCCHN compared with control normal mucosa from patients
      without cancer, implicating this ligand-receptor pair in an autocrine growth
      pathway early in the molecular pathogenesis of this disease. In this report, we
      examined the hypothesis that the action of RA on the mucosa of the upper
      aerodigestive tract is mediated via downregulation of steady-state TGF-alpha
      and/or EGFR mRNA levels. Following exposure to all-trans-RA, a series of SCCHN
      cell lines demonstrated a 35.4% reduction in TGF-alpha mRNA expression (P =
      0.022) and 58.5% reduction in EGFR mRNA (P = 0.0027). Nuclear run-on analysis
      indicated that the RA-mediated reduction of TGF-alpha and EGFR steady-state mRNA
      levels was a result of decreased gene transcription. These results suggest that
      the clinical effects of RA in SCCHN patients may be due to a downmodulation of
      TGF-alpha and EGFR mRNA production.

PMID- 8574973
TI  - Energy transfer primers: a new fluorescence labeling paradigm for DNA sequencing
      and analysis.

PMID- 8574974
TI  - Cornea and external disease.

PMID- 8574975
TI  - Apoptosis and oncosis in ocular disease.

PMID- 8574976
TI  - Effect of retinoic acid on expression of transforming growth factor-beta by
      retinal pigment epithelial cells in culture.
AB  - OBJECTIVE: To study the effect of retinoic acid on the expression of transforming
      growth factor-beta (TGF-beta) by human retinal pigment epithelial (RPE) cells in
      culture. MAIN OUTCOME MEASURES: Expression of TGF-beta 1 by RPE cells after 24
      hours in culture at the messenger RNA level (Northern analysis) and the protein
      level (enzyme-linked immunosorbent assay [ELISA]). RESULTS: On the basis of cell
      morphology, growth characteristics and the results of immunohistochemical
      studies, we concluded that the cells used in these experiments were RPE in
      origin. Immunohistochemical studies confirmed TGF-beta 1 expression by the RPE
      cells in culture. Densitometry showed that retinoic acid reduced the level of TGF
      beta 1 mRNA expression by 41% compared with control samples. ELISA showed that
      retinoic acid inhibited TGF-beta expression when compared with the baseline level
      of TGF-beta in media from RPE cells in culture. CONCLUSIONS: These findings may
      have implications for the pharmacotherapy of proliferative vitreoretinopathy.

PMID- 8574977
TI  - Metastasis to the optic nerve: clinicopathological correlations.
AB  - OBJECTIVE: To describe the clinical, radiologic and histopathological features of
      two cases of carcinoma metastatic to the optic nerve with different pathways of
      spread. DESIGN: Chart review. SETTING: Oncology clinic in Montreal. PATIENTS: One
      patient previously treated for breast carcinoma and one patient previously
      treated for small-cell carcinoma of the lung. RESULTS: The patient with breast
      carcinoma was found to have an elevated mass involving her right optic nerve
      head. This finding was confirmed by B-scan ultrasonography. The other patient
      initially presented with left retinal metastasis and subsequently manifested
      massive secondary involvement of the ipsilateral optic nerve, documented by
      computed tomography. Both patients were initially treated with radiotherapy to
      the eye and orbit, but postmortem histopathological study showed that this
      treatment had little effect on the tumour. CONCLUSIONS: The histopathological
      observations suggest that if radiotherapy is to be used in the treatment of
      metastasis to the optic nerve, the dosage of radiation should be higher than that
      recommended for the treatment of choroidal metastasis.

PMID- 8574978
TI  - Actinic keratosis and dysplasia of the conjunctiva: a clinicopathological study
      of 45 cases.
AB  - OBJECTIVE: To characterize precancerous conjunctival intraepithelial tumours on
      file at the Armed Forces Institute of Pathology (AFIP). DESIGN: Chart review.
      SETTING: Registry of Ophthalmic Pathology of the AFIP. NUMBERS: Forty-five
      patients with intraepithelial neoplastic lesions of the conjunctiva followed for
      at least 2 years. MAIN OUTCOME MEASURES: Extent; papillomatous pattern; degree of
      parakeratosis, hyperkeratosis and atypia; and amount of solar elastosis. RESULTS:
      Based on their histologic appearance, 24 cases were classified as actinic
      keratosis and 21 cases as dysplasia. Clinically, lesions classified as actinic
      keratosis tended to be focal and leukoplakic, whereas those classified as
      dysplasia tended to be diffuse and gelatinous. Two of the lesions classified as
      actinic keratosis recurred, compared with 13 of the lesions classified as
      dysplasia. In one patient with dysplasia locally invasive squamous cell carcinoma
      developed after numerous recurrences, requiring orbital exenteration. The degree
      of atypia was not correlated with recurrence in either group. CONCLUSIONS: Most
      intraepithelial neoplastic lesions of the conjunctiva can be readily diagnosed by
      the ophthalmic pathologist as either actinic keratosis or dysplasia.

PMID- 8574979
TI  - Peribulbar injection of bupivacaine for the control of pain and nausea in
      vitreoretinal surgery.

PMID- 8574980
TI  - Pupil mnemonics.

PMID- 8574981
TI  - Retinal and choroidal embolization following soft-tissue maxillary injection of
      corticosteroids.

PMID- 8574982
TI  - Sebaceous carcinoma of the eyelid in an immunocompromised patient with Muir-Torre
      syndrome.

PMID- 8574983
TI  - Reversible loss of vision due to posterior ischemic optic neuropathy.

PMID- 8574984
TI  - Psychiatry--meeting the challenges: I am worried, I am encouraged.

PMID- 8574985
TI  - Is a diagnosis-based classification system appropriate for funding psychiatric
      care in Alberta?
AB  - OBJECTIVE: This study evaluated the appropriateness of the Refined Group Number
      (RGN) classification system for funding psychiatric discharges in Alberta.
      METHOD: Multiple regression was used to calculate the amount of variation
      explained (R2) in length of stay by RGNs for psychiatric discharges. The
      distribution of short-stay cases (less than 5 days) was also reviewed. RESULTS:
      The R2 value was higher than those from American studies (0.284 versus less than
      0.10) for psychiatric discharges. The length of stay distribution by RGN
      indicated that the mean was not representative of typical cases. Short-stay cases
      made up the majority of cases from rural hospitals and had a negative impact on
      the average length of stay. CONCLUSIONS: The RGN methodology performed better
      than diagnosis-based classification systems in the United States. However, there
      were significant weaknesses in the classification system which suggest that a
      funding system using the RGN grouper would result in inequitable funding for
      psychiatric discharges.

PMID- 8574986
TI  - The psychopathology of incarcerated self-mutilators.
AB  - OBJECTIVE: To investigate the symptomatology of severe psychopathology reported
      by male incarcerated self-multilators. METHOD: Comparisons were made with a
      nonmutilating incarcerated group and a nonincarcerated, nonmutilator group.
      RESULTS: A distinctive pattern of symptomatology emerged. Self-mutilators
      evidenced a wide range of elevated scores on general measures of
      psychological/psychiatric symptoms, particularly depression and hostility.
      Aspects of hostility that distinguished self-mutilators for other groups included
      the urge to act out hostile feelings, critical feelings towards others, paranoid
      feelings of hostility and guilt. Self-mutilators demonstrated substantial
      problems with substance abuse, particularly alcohol. CONCLUSION: A pattern of
      passive-aggressive, schizoid and avoidant personality styles distinguished self
      mutilators from other groups.

PMID- 8574987
TI  - The five-factor model of personality in borderline and nonborderline personality
      disorders.
AB  - OBJECTIVE: The purpose of this study was to examine to what extent the phenomena
      associated with a diagnosis of borderline personality disorder (BPD) can be
      described by the five-factor model of personality. METHOD: The sample consisted
      of female patients with BPD (n = 29) and a control group with a mixture of
      nonborderline personality disorders (n = 30). All subjects were given the NEO-PI
      R. RESULTS: Borderline patients differed from community norms on all five
      factors, and were particularly high on Neuroticism, and particularly low on
      Agreeableness. The scores on the five factors did not differ significantly
      between the 2 clinical groups. Two facets of the conscientiousness scale
      (competence and deliberation) were significantly lower in the BPD group.
      CONCLUSIONS: Dimensional profiles only partially account for the clinical
      symptomatology seen in formally diagnosed cases of BPD.

PMID- 8574988
TI  - Small area variation in the utilization of mental health services: implications
      for health planning and allocation of resources.
AB  - OBJECTIVE: To determine the variables associated with utilization of mental
      health services and to develop a planning model to predict service utilization
      that incorporates these factors. METHOD: A regression analysis of service
      utilization and demographic characteristics was used to assess the relative
      importance of alternative service, supply of psychiatrists and demographics in
      explaining variations of services use. A model using socioeconomic factors was
      applied to the population to predict need. RESULTS: The percentage of divorced
      males was the only factor significantly and positively correlated with the
      utilization of hospital inpatient and provincial psychiatric beds. Predicted need
      exceeds utilization in 7 out of 10 areas for all services. CONCLUSIONS: Small
      area variations in inpatient psychiatric utilization is correlated with community
      characteristics, not supply of psychiatrists or utilization of alternative
      services. A model has been developed using census data to allocate resources
      according to need.

PMID- 8574989
TI  - Treatment of acute bipolar depression: a review of the literature.
AB  - OBJECTIVE: Our goal was to ascertain the efficacy of various antidepressant
      treatments for acute bipolar depression. METHOD: English articles that reported
      on the efficacy of antidepressant treatments in bipolar depression were located
      by computerized Medline and manual search. These studies were systematically
      reviewed and response rates for each treatment were computed. RESULTS: The
      available data suggest that mood stabilizers, MAOIs, cyclic antidepressants, and
      ECT are all effective in treating bipolar depression. All antidepressant
      treatments with the exception of mood stabilizers have been reported to induce a
      manic/hypomanic switch. CONCLUSIONS: It is recommended that mood stabilizers may
      be the first step of treatment, followed by the addition of an antidepressant,
      especially a cyclic antidepressant. The specific symptoms profile of individual
      patients, such as anergic or psychotic features, may indicate more specific
      treatment options. ECT is an important measure for those who are pharmacotherapy
      resistant or psychotic.

PMID- 8574990
TI  - Management of suspected neuroleptic malignant syndrome.
AB  - OBJECTIVE: Neuroleptic Malignant Syndrome (NMS) is a rare but potentially lethal
      form of drug-induced hyperthermia. The objective of this paper is to provide data
      regarding early and suspected cases as well as offer guidelines for managing this
      condition. Knowledge of suspected cases will lead to early recognition and prompt
      management of this condition in the future. METHOD: To address the gap in
      knowledge, we present 2 case reports of patients with early NMS-like symptoms.
      The case reports are followed by a brief review of the literature on differential
      diagnoses, risk factors, early signs and treatment data. CONCLUSIONS: The most
      rational approach to treating NMS entails a hierarchy of interventions determined
      by the severity and progression of symptoms.

PMID- 8574991
TI  - [Markers of depression regarding DSM and popular diagnosis: an analysis of
      concordance in Quebec patients].
AB  - OBJECTIVE: To query the universality of affective disorder markers, particularly
      the level of consistency between DSM diagnostic criteria and the criteria
      implicit in popular diagnoses. METHOD: Utilization of data from the Sante Quebec
      (1987) survey to compare depression markers reported by respondents who
      identified themselves or were identified by a member of their household as
      "suffering from depression" and markers underlying DSM-III diagnostic criteria.
      RESULTS: A popular diagnosis of depression is implicitly different from a
      psychiatric diagnosis considering an interdiagnosis similarity of 9.5%.
      CONCLUSION: It is therefore important to become more knowledgeable about the
      markers underlying diagnosis of affective disorders.

PMID- 8574992
TI  - Effect of risperidone on polydipsia and hyponatremia in schizophrenia.

PMID- 8574993
TI  - Depression associated with isotretinoin therapy.

PMID- 8574994
TI  - Treatment of late-onset agoraphobia secondary to depression.

PMID- 8574995
TI  - The disempowerment of psychiatrists.

PMID- 8574996
TI  - Intracellular signalling through protein kinases in the heart.
AB  - Protein kinases play important roles in intracellular signalling pathways in
      probably all cells. In the heart, they are involved in the regulation of ion
      handling, contractility, fuel metabolism and growth. In this review, we discuss
      the consequences of activation of protein kinases known to be expressed in the
      heart. We concentrate principally on the following: cyclic AMP-dependent protein
      kinase, protein kinase C, mitogen-activated protein kinase, Ca2+/calmodulin
      dependent protein kinases and pyruvate dehydrogenase kinase.

PMID- 8574997
TI  - Free radicals and intracellular events associated with cerebrovascular spasm.

PMID- 8574999
TI  - Angiotensin II signal transduction and the mitogen-activated protein kinase
      pathway.
AB  - In this review, the angiotensin-II-mediated signal transduction pathways involved
      in vascular smooth muscle cell growth are discussed. Classical pathways involving
      phospholipase C and protein kinase C, as well as the mitogen-activated protein
      kinase pathway, are common signal transduction pathways activated by a variety of
      growth factors to stimulate cell growth. Besides its vasoconstrictor activity,
      angiotensin II stimulates hypertrophy of vascular smooth muscle cells and is
      involved in neointimal proliferation following balloon angioplasty. Understanding
      angiotensin-II-stimulated signaling events, as well as the crosstalk among
      signaling pathways, may form the basis for the development of new therapies for
      hypertension and restenosis.

PMID- 8574998
TI  - Regulation of ribosomal DNA transcription during neonatal cardiomyocyte
      hypertrophy.
AB  - In summary, the increased capacity for protein synthesis that is a constant
      feature in all forms of cardiac hypertrophy is largely mediated by accelerated
      ribosome biogenesis. Experiments with neonatal cardiomyocytes in culture indicate
      that the activity of the rDNA transcription factor, UBF, may contribute to the
      regulation of rDNA transcription during the hypertrophic growth process. The
      observations of parallel responses in three different models of neonatal
      cardiomyocyte hypertrophy suggest that further studies on the regulation of UBF
      should lead to a clearer understanding of the pathways that lead to hypertrophy.
      Possible alterations in the activities and/or amounts of other factors associated
      with rDNA transcription including SL-1, TFIC and the polymerase I enzyme itself,
      may also contribute to the regulation of cardiomyocyte growth; however, this
      remains to be demonstrated.

PMID- 8575000
TI  - Phospholipase-A2-dependent signalling in the heart.

PMID- 8575001
TI  - The role of tyrosine phosphorylation in angiotensin II-mediated intracellular
      signalling.

PMID- 8575002
TI  - Molecular signalling mechanisms controlling growth and function of cardiac
      fibroblasts.
AB  - Cardiac fibroblasts appear to be important in producing and maintaining the
      extracellular matrix (ECM) of the heart. The abnormal proliferation of cardiac
      fibroblasts and deposition of the ECM protein, collagen, associated with
      hypertension and myocardial infarction, may adversely affect the performance of
      the heart. Several groups of factors affect collagen gene expression and/or
      growth of cardiac fibroblasts. Angiotensin II, aldosterone and endothelins play a
      central role in the remodeling of the ECM in hypertension, and decrease
      collagenase activity and/or increase collagen synthesis in cultured cells.
      Regulatory peptides that are generally elevated at sites of injury, such as TGF
      beta 1 and PDGF, increase collagen synthesis and/or stimulate mitogenesis.
      Mechanical stretch enhances collagen expression and cell proliferation, responses
      which could in part be due to integrin activation. Cytokines may stimulate or
      inhibit cell growth, the latter through prostaglandin formation. Angiotensin II
      is a principal determinant in vivo of cardiac fibroplasia and synthesis of the
      ECM proteins, collagen and fibronectin. Cardiac fibroblasts possess G-protein
      coupled AT1 receptors for angiotensin II that couple to activation of multiple
      signalling pathways, including: phospholipase C-beta, with the subsequent release
      of Ca2+ from intracellular stores and activation of protein kinase C, mitogen
      activated protein kinases, tyrosine kinases, phospholipase D, phosphatidic acid
      formation, and the STAT family of transcription factors. Cardiac fibroblasts
      respond to angiotensin II with hyperplastic/hypertrophic growth, and increased
      expression of collagen, fibronectin, and integrins. The mechanisms by which the
      AT1 receptor activates multiple signalling pathways are not known, although the
      receptor might interact at some level with both integrins and cytokine receptors.
      Different signalling pathways of the AT1 receptor may subserve different cellular
      responses, such as mitogenesis, ECM synthesis, or an inflammatory/stress
      response. Crosstalk among the signalling pathways of the AT1 receptor, and those
      of G-protein, cytokine, and growth-factor receptors, may determine the ultimate
      response of the cell.

PMID- 8575003
TI  - Signalling mechanisms in the regulation of vascular cell migration.
AB  - The migration of arterial vascular smooth muscle cells (VSMC) is thought to play
      a central role in atherogenesis and restenosis. The migration of several other
      cell types, including monocytes, T-lymphocytes and endothelial cells is also
      involved in the development of the mature atherosclerotic lesion. Several defined
      growth factors, cytokines and extracellular matrix components which are released
      at the sites of lesions have been implicated in the regulation of migration of
      VSMC and other lesion-associated cells. Platelet-derived growth factor BB
      homodimer of PDGF (PDGF-BB) is strongly implicated in neo-intima formation in
      vivo and is the most potent known chemoattractant for VSMC in vitro. Dynamic
      interactions between cell surface adhesive receptors (integrins) for ECM
      components, organisation of the actin cytoskeleton and the turnover of focal
      adhesions are all key processes in cell locomotion and migration. The signal
      transduction pathways which mediate the chemotactic effects of PDGF-BB and other
      migration factors on VSMC are unknown, but several classes of cellular components
      are implicated including components associated with focal adhesions, small GTP
      binding proteins of the rho family, and certain substrates of the PDGF beta
      receptor. Tyrosine phosphorylation of the novel focal adhesion-associated protein
      tyrosine kinase, p125 focal adhesion kinase (p125FAK), is regulated by integrins
      and by several factors which alter actin cytoskeletal organisation. Recent
      findings suggest that tyrosine phosphorylation of p125FAK and other focal
      adhesion-associated proteins may be implicated in the chemotactic response of
      VSMC to PDGF-BB. The migratory response to PDGF-BB may be dependent on both
      ligand isoform bio-availability and on receptor-isotype expression as well as on
      down-stream signalling events. Ultimately, cell migration in vivo will be
      determined by a complex array of diverse extracellular molecules organised in
      intercellular paracrine/autocrine networks as well as multiple interacting
      intracellular signal transduction pathways.

PMID- 8575004
TI  - Cell cycle control mechanisms and their role in cardiac growth.

PMID- 8575005
TI  - Signal transduction mechanisms controlling cardiac contractility and their
      alterations in chronic heart failure.

PMID- 8575006
TI  - Mitogen-responsive nuclear factors that mediate growth control signals in
      vascular myocytes.

PMID- 8575007
TI  - Nitric oxide signaling in ischemic heart.
AB  - OBJECTIVE: Several recent studies have implicated a role of endogenous nitric
      oxide (NO) in the pathophysiology of myocardial ischemic/reperfusion injury.
      However, the mechanism by which NO exerts its beneficial/detrimental effects
      remains unknown. This study examined the intracellular signaling of NO by
      studying the role of the NO-cGMP signaling pathway on the phospho-diesteratic
      breakdown and turnover of phosphoinositides during myocardial ischemia and
      reperfusion. METHODS: Isolated working rat hearts were made ischemic for 30 min
      followed by 30 min of reperfusion. A separate group of hearts were pre-perfused
      with 3 mM L-arginine for 10 min prior to ischemia. The release of NO was
      monitored using an on-line amperometric sensor. The aortic flow and developed
      pressure were examined to determine the effects of L-arginine on
      ischemic/reperfusion injury. For signal transduction experiments, sarcolemmal
      membranes were radiolabeled by perfusing the isolated hearts with [3H]myoinositol
      and [14C]arachidonic acid. Hearts were then perfused for 10 min in the presence
      or absence of L-arginine via the Langendorff mode. Ischemia was induced for 30
      min followed by 30 min of reperfusion. Experiments were terminated before L
      arginine and after L-arginine treatment, after ischemia, and during reperfusion.
      Biopsies were processed to determine the isotopic incorporation into various
      phosphoinositols as well as phosphatidic acid and diacylglycerol. cGMP was
      assayed by radioimmunoassay and SOD content was determined by enzymatic analysis.
      RESULTS: The release of NO was diminished following ischemia and reperfusion and
      was augmented by L-arginine. L-Arginine reduced ischemic/reperfusion injury as
      evidenced by the enhanced myocardial functional recovery. cGMP, which remained
      unaffected by ischemia and reperfusion, was stimulated significantly after L
      arginine treatment. The cGMP level persisted up to 10 min of reperfusion and then
      dropped slightly. Reperfusion of ischemic myocardium resulted in significant
      accumulation of radiolabeled inositol phosphate, inositol bisphosphate, and
      inositol triphosphate. Isotopic incorporation of [3H]inositol into
      phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol
      4,5-bisphosphate was increased significantly during reperfusion. Reperfusion of
      the ischemic heart prelabeled with [14C]-arachidonic acid resulted in modest
      increases in [14C]diacylglycerol and [14C]phosphatidic acid. Pretreatment of the
      heart with L-arginine significantly reversed this enhanced phosphodiesteratic
      breakdown during ischemia and early reperfusion. However, at the end of the
      reperfusion the inhibitory effect of L-arginine on the phosphodiesterases seems
      to be reduced. In L-arginine-treated hearts, SOD activity was progressively
      decreased with the duration of reperfusion time. CONCLUSIONS: The results suggest
      for the first time that NO plays a significant role in transmembrane signaling in
      the ischemic myocardium. The signaling seems to be transmitted via cGMP and
      opposes the effects of phosphodiesterases by inhibiting the ischemia/reperfusion
      induced phosphodiesteratic breakdown. This signaling effect appears to be reduced
      as reperfusion progresses. These results, when viewed in the light of free
      radical chemistry of NO, suggest that such on- and off-signaling of NO may be
      linked to its interaction with the superoxide radical generated during the
      reperfusion of ischemic myocardium.

PMID- 8575008
TI  - Alterations in G-protein-regulated transmembrane signalling induced in murine
      myocardium by coxsackievirus B3 infection.
AB  - OBJECTIVE: Cardiomyopathy is usually associated with marked alterations in
      myocardial transmembrane signalling. Although acute viral myocarditis may result
      in chronic cardiomyopathy in some cases, the possible consequences of viral
      infection on function of the myocardial signal-transducing complex have not been
      explored. Therefore, the present study was designed to investigate the G-protein
      regulated adenylyl cyclase signalling system in murine myocardium during
      myocarditis induced by coxsackievirus B3 (CVB3) infection. METHODS: We examined
      the functional characteristics of adenylyl cyclase as well as the function and
      distribution of beta-adrenoceptors, m-cholinoceptors and G-proteins in myocardial
      plasma membranes isolated from the hearts of mice with acute (7 days pi) or late
      phase (21 days pi) myocarditis and the obtained results were compared with the
      corresponding data determined in age-matched controls. RESULTS: While the basal
      adenylyl cyclase activity was not significantly altered, the ability of
      forskolin, sodium fluoride and GTP gamma S to activate adenylyl cyclase was
      lowered by about 20% in samples from virus-infected animals. The level of Gs
      alpha in myocardial plasma membranes as well as the functional activity of Gs
      alpha was not affected by viral infection, but the Gi alpha content was increased
      by about 20%. The total number of beta-adrenoceptors in myocardial plasma
      membranes increased by about 12-15% due to higher content of the beta 2
      adrenoceptor subtype. Although the agonist-binding parameters of beta
      adrenoceptors were not significantly altered, the ability of these receptors to
      mediate stimulation of adenylate cyclase was markedly diminished (by 56-80%). The
      total number of m-cholinoceptors in samples derived from virus-infected mice
      increased considerably (by 29-59%) and a significant proportion of the receptors
      shifted to a higher affinity status, but their ability to transduce agonist
      signals was impaired. CONCLUSIONS: These data are the first to demonstrate that
      several different sites of the myocardial G-protein-regulated adenylyl cyclase
      signalling complex are significantly altered in acute as well as in late phase of
      CVB3-induced myocarditis.

PMID- 8575009
TI  - Myocardial Gi alpha-protein levels in patients with hypertensive cardiac
      hypertrophy, ischemic heart disease and cardiogenic shock.
AB  - OBJECTIVE: Increased inhibitory G-protein alpha-subunits (Gi alpha) have been
      reported to be related to adenylyl cyclase desensitization in the failing human
      heart. In order to investigate whether this cellular alteration occurs already at
      the stage of hypertensive cardiac hypertrophy or in catecholamine-refractory
      cardiogenic shock, Gi alpha levels were studied in myocardial samples from
      patients with hypertensive cardiac hypertrophy, coronary heart disease without
      heart failure and from patients with cardiogenic shock on high-dose catecholamine
      therapy as well as from patients without evidence of heart disease. METHODS: Gi
      alpha was quantified with pertussis-toxin-catalyzed 32P-ADP-ribosylation and with
      a radioimmunoassay in myocardial samples from patients within 16 h of death. The
      radioimmunoassay was constructed with recombinant G-protein alpha-subunits (rGi
      alpha 1) from transformed E. coli harbouring the full-length cDNA of Gi alpha 1,
      iodinated peptide 125I-KENLKDCGLF and immunoprecipitating antiserum (MB 1) raised
      against the synthetic peptide (KENLKDCGLF) in rabbits. RESULTS: Pertussis toxin
      substrates and immunochemical Gi alpha remained stable up to 80 h following
      storage at room temperature in myocardium obtained during cardiac
      transplantation. Gs alpha, adenylyl cyclase, beta-adrenoceptors and inhibitory
      receptors were not stable and could not be determined. Increases in myocardial Gi
      alpha of 65-82% of both pertussis toxin substrates and immunologically quantified
      Gi alpha were observed in hypertensive cardiac hypertrophy. Catecholamine therapy
      in patients who died of catecholamine-refractory shock increased myocardial Gi
      alpha by 225% compared to myocardium from patients with coronary heart disease
      without heart failure and without catecholamine therapy or compared to control
      myocardium. CONCLUSION: These findings provide evidence than an increase in
      myocardial Gi alpha-proteins could be of relevance in pathological conditions
      other than chronic heart failure. Since an increase in Gi alpha levels already
      occurs in hypertensive cardiac hypertrophy, it could play a role in contributing
      to the development of contractile dysfunction and heart failure in later stages
      of the syndrome. Finally, an increase in Gi alpha could be one mechanism
      contributing to catecholamine refractoriness in shock. This could provide a
      target for pharmacological treatment in this condition.

PMID- 8575010
TI  - Lazaroids and deferoxamine attenuate the intracellular effects of oxyhaemoglobin
      in vascular smooth muscle.
AB  - OBJECTIVES: While it is probable that the cerebrovascular spasm which occurs
      after subarachnoid haemorrhage results from the action of haemoglobin, the
      mechanism of that process remains unclear. These studies were thus designed to
      test the hypothesis that the action of oxyhaemoglobin results from the iron
      catalyzed formation of free radicals and subsequent lipid peroxidation resulting
      in intracellular changes in the second messengers for contraction. METHODS:
      Levels of intracellular calcium and of inositol (1,4,5)-trisphosphate were
      measured in cultured vascular smooth muscle cells derived from primate cerebral
      arteries. Contractility of rings of canine cerebral vessels were examined in
      vitro using standard pharmacological techniques. Vessels in spasm were obtained
      from the "two haemorrhage" canine model and the presence of vasospasm was
      confirmed angiographically. In each case, the effects of oxyhaemoglobin and
      sometimes of free radicals generated from iron salts were examined in the
      presence and in the absence of free-radical scavenging agents or the iron
      chelating agent, deferoxamine. RESULTS: Oxyhaemoglobin produces a slowly
      developing sustained contraction of arterial rings which is accompanied by a
      sustained elevation of intracellular calcium. It also produces a transient but
      significant elevation of inositol (1,4,5)-trisphosphate, but this is not
      correlated with the development of sustained constriction. Deferoxamine and the
      lazaroid compounds U-74389G and U-83836E were effective in preventing the effects
      of oxyhaemoglobin and free radicals in the models tested, although in vessels in
      spasm, all effects were smaller. CONCLUSIONS: The present study provides results
      which are consistent with the hypothesis that the actions of haemoglobin on
      vascular smooth muscle are mediated by the formation of free radicals which
      subsequently affect intracellular calcium concentrations. This also implies that
      agents which impair free radical production or other processes leading to iron
      catalyzed lipid peroxidation, are of potential value in cerebrovascular spasm.

PMID- 8575011
TI  - Precise sequence assignment of replication origin in the control region of chick
      mitochondrial DNA relative to 5' and 3' D-loop ends, secondary structure, DNA
      synthesis, and protein binding.
AB  - The data reported identify for the first time the sequence of an avian
      mitochondrial heavy-strand replication origin, OH, located only about 12
      nucleotides (nt) downstream from the conserved sequence block CSB-1, as well as
      the sequence of premature synthesis arrest of the 781 (+/-1) nt D-loop strand,
      only 6-7 nt downstream from a TAS-like (termination-associated) element. Both
      sites are associated with putative cruciform secondary structures. A major
      sequence-specific DNA-binding/cleavage site of a potential regulatory protein,
      the approximately 36-kDa aMDP1 (shown previously to stimulate mtDNA synthesis),
      is located about 90 nt upstream of OH. Correlated in vivo analysis of avian
      genome-length mtDNA replication provides missing evidence on the functional
      equivalence of D-loop origin with nascent initiation, and on the direction,
      asymmetry and temporal aspects of a full round of replication. The importance of
      the results to understanding the regulation of linked replication/transcription
      and the unusual sequence evolution of avian mtDNA is

PMID- 8575012
TI  - Multi-copy nuclear pseudogenes of mitochondrial DNA reveal recent acute genetic
      changes in the human genome.
AB  - Four nuclear pseudogenes homologous to the 10031-10195-bp region of the human
      mitochondrial genome were detected by constant denaturant capillary
      electrophoresis. Among them, one pseudogene is present as at least five copies in
      each cell, in accordance with our previous observations of multi-copy
      mitochondrial DNA pseudogenes. The presence of multiple identical copies of
      pseudogenes suggests that the human genome underwent a series of genetic changes,
      including gene amplifications, very recently in evolutionary history, i.e.,
      within the last 390000 years.

PMID- 8575013
TI  - Creation of an initiation codon by RNA editing in the coxI transcript from tomato
      mitochondria.
AB  - Nucleotide-sequence analysis showed that the gene for cytochrome oxidase subunit
      I (coxI) from tomato mitochondrial DNA has an ACG codon at a conserved position
      corresponding to an ATG initiation codon in other higher-plant coxI genes. cDNA
      sequence analysis of the coxI transcripts showed that 15 positions in the genomic
      DNA were converted from C to U in the transcripts by RNA editing. One of the
      editing events is observed at the indicated ACG codon, producing an ATG
      initiation codon. The nucleotide sequences of 37 cDNA clones showed that the
      initiation codon was created in 32 out of the 37 clones, while nucleotide
      positions 254 and 11 were edited in 37 and 34 of the 37 clones examined,
      respectively, suggesting that creation of the initiation codon is a post
      transcriptional event. The BamHI site at nucleotide position 757-762 within the
      coxI genomic DNA was altered in all 97 cDNA clones examined, demonstrating that
      RNA editing at this site in the transcripts is very common. RNA editing takes
      place to a lesser extent at the initiation codon, compared with editing at
      internal position 254. This indicates that editing is either a random process or
      that it involves a mechanism favoring less RNA editing in the initiation codon
      than in internal sites.

PMID- 8575014
TI  - The genes encoding subunit 3 of NADH dehydrogenase and ribosomal protein S12 are
      co-transcribed and edited in Pinus sylvestris (L.) mitochondria.
AB  - The nucleotide sequence of the region encoding NADH dehydrogenase subunit 3 and
      ribosomal protein S12 from Pinus sylvestris (L.) mitochondrial DNA (mtDNA) has
      been determined. A sequence comparison of this region with six individual cDNA
      clones prepared by RT-PCR revealed 35 C-to-T differences, showing the occurrence
      of RNA editing. All but one of these alterations in mRNA sequence change codon
      identities to specify amino acid better conserved in evolution. Most of these
      modifications take place within the nad3 gene changing 20% of the amino-acid
      sequence, which is much more than in angiosperms. Of six cDNA clones
      investigated, four clones of nad3 were differentially edited, but the editing of
      the rps12 sequences was identical. As in angiosperms, the two genes are separated
      by a short sequence of 52 bp, which is not edited. Two transcripts of about 0.9
      kb and 1.2 kb, each encoding both proteins, have been detected by Northern
      hybridisation. The hybridisation of nad3 and rps12 probes with pine mtDNA
      digested with different restriction enzymes indicates that both genes are present
      in a single copy in pine mtDNA. The analysis of PCR amplification products with
      gene-specific primers shows a conserved order of these genes in a wide range of
      gymnosperms.

PMID- 8575015
TI  - Isolation and characterization of Pioneer1, a novel Chlamydomonas transposable
      element.
AB  - During the course of this study a novel family of Chlamydomonas mobile elements
      has been identified in natural isolate strain 224. The first member of this class
      to be characterized, a 2.8-kb element named Pioneer1, was trapped in an intron of
      the nitrate reductase structural gene, NIT1. This element has been cloned and
      completely sequenced and found to be unusual in structure. Pioneer elements are
      present in a very low-copy number of three per genome in strain 224. The copy
      number increased by one upon transposition of Pioneer1. Hybridization of Pioneer1
      to a variety of Chlamydomonas strains confirmed that this element differed from
      previously described Chlamydomonas transposons. It also indicated that related
      elements are present in low-copy number in natural isolate strains 356 and S1D2,
      but not in the most commonly used laboratory strains 137c and 21 gr. For these
      reasons, members of the Pioneer family might prove useful as insertional
      mutagens.

PMID- 8575016
TI  - Isolation of a Chlamydomonas reinhardtii telomere by functional complementation
      in yeast.
AB  - We attempted to determine whether Chlamydomonas reinhardtii telomeres, which do
      not form G-quartet structures readily in vitro, are able to nucleate telomere
      addition in Saccharomyces cerevisiae. Restricted C. reinhardtii genomic DNA was
      ligated to a linear S. cerevisiae vector lacking a telomere. A C. reinhardtii
      telomere ligated to this unprotected end allowed vector replication as a linear
      DNA molecule in S. cerevisiae. DNA sequencing revealed common [T4AG3]n and
      variant T6AG3 and T5AG3 C. reinhardtii telomere repeats capped by S. cerevisiae
      telomere repeat units. The recognition of a C. reinhardtii telomere by the
      telomere maintenance machinery of S. cerevisiae is consistent with a common theme
      for telomere structure in organisms with divergent telomere repeats.

PMID- 8575017
TI  - A two-reporter gene system for the analysis of bi-directional transcription from
      the divergent MAL6T-MAL6S promoter in Saccharomyces cerevisiae.
AB  - Many sets of genes in Saccharomyces cerevisiae are divergently transcribed, but
      at present there are no vectors generally available for the simultaneous analysis
      of divergent transcription from these promoters. In the present study MEL1 and
      lacZ were used to construct a vector capable of measuring the divergent
      expression initiated by the MAL6T-MAL6S bi-directional promoter. Our observations
      demonstrate that the expression of both reporter genes was regulated in a similar
      fashion to the native MAL6T and MAL6S genes, and that induction was dependent
      upon the presence of a functional MALR activator gene. The results confirmed that
      the MAL6T-MAL6S promoter was co-ordinately regulated, repressed by glucose,
      induced by maltose, and that basal expression was more active in the MAL6S
      direction than in the MAL6T direction.

PMID- 8575018
TI  - Two novel genes involved in the sexual development of Schizosaccharomyces pombe.
AB  - We isolated two sterile mutants of Schizosaccharomyces pombe. One of them was
      mapped close to ste13 (8 cM). Since it turned out to be allelic with the hitherto
      unmapped ral2, its linkage with ste13 localizes ral2 on the right arm of
      chromosome II. The other mutant defines a novel class-I ste gene, ste15, closely
      linked to ste7 (4 cM) on chromosome I. ste15 is conjugation-specific and acts
      upstream of pat1 and ras1. During its genetic analysis, a phenotypic suppression
      of ste12-N9 was observed which was caused by mutations in the unlinked gene ssw1.

PMID- 8575019
TI  - Localization of lipase genes on Candida rugosa chromosomes.
AB  - In the yeast Candida rugosa the lipase isozymes are encoded by a family of genes,
      five of which have been cloned and sequenced in our laboratory. In this paper we
      report on the identification and preliminary characterization of two new related
      sequences, thus extending this multigene family to seven members. The total DNA
      content of Candida cells was estimated by laser flow-cytometry at about 20 Mb.
      Eight chromosomes with sizes ranging between 100 kb and 2.1 Mb, as determined by
      comparison with S. cerevisiae chromosomal bands, were resolved by pulsed-field
      gel electrophoresis. The lipase-encoding genes were localized on chromosome I,
      therefore suggesting that they have originated through multiple duplication
      events of an ancestral gene.

PMID- 8575020
TI  - Inactivation of a single-2A phosphoprotein phosphatase is lethal in Neurospora
      crassa.
AB  - A PCR approach, employing the use of degenerate oligonucleotide mixtures, was
      used to isolate pph-1, a type-2A protein phosphatase (catalytic subunit)-encoding
      gene, from Neurospora crassa. The isolated single copy gene is 1327 nucleotides
      in length, contains four putative introns and encodes a 310 amino-acid
      polypeptide. pph-1 is located between pdx-1 and col-4 on the right arm of
      N.crassa linkage group IV. pph-1 transcript levels are highest during the first
      hours of conidial germination. Failure to obtain viable progeny in which pph-1
      had been inactivated via the repeat-induced point (RIP) mutation process, and
      evidence that nuclei harboring a disrupted pph-1 gene could only be maintained in
      a heterokaryon, indicated that a functional pph-1 gene is essential for fungal
      growth. This is the first report providing evidence that inactivation of a single
      type-2A protein phosphatase gene results in a lethal phenotype in fungi.

PMID- 8575021
TI  - Cloning and expression of an Aspergillus kawachii endo-1,4-beta-xylanase gene in
      Saccharomyces cerevisiae.
AB  - First-strand cDNA was prepared from mRNA isolated from Aspergillus kawachii
      IFO4308 and the beta-xylanase gene (xynC) amplified by using the polymerase chain
      reaction (PCR) technique. This gene was inserted between the yeast
      phosphoglycerate kinase (PGK1) gene promoter (PGK1p) and terminator (PGK1T)
      sequences. The PGK1p-xynC-PGK1T construct (designated XYN3) was cloned into a
      multicopy episomal plasmid and the XYN3 gene was expressed in Saccharomyces
      cerevisiae. Functional beta-xylanase (Xyn3) was produced and secreted by the
      recombinant yeast. Xyn3 was stable between 30 and 50 degrees C, and the optimum
      temperature and pH were shown to be at 60 degrees C and lower than pH 3,
      respectively. An autoselective furl::LEU2 XYN3 recombinant strain was developed
      that allowed beta-xylanase production at a level of 300 nkat/ml in a non
      selective complex medium.

PMID- 8575022
TI  - Integrative and replicative transformation of Penicillium canescens with a
      heterologous nitrate-reductase gene.
AB  - A wild isolate of Penicillium canescens was subjected to mutagenesis, and 150
      chlorate-resistant mutants were isolated and classified in respect of their
      ability to utilize various nitrogen sources. Strains supposedly deficient in
      nitrate reductase have been transformed with the nitrate-reductase gene from
      Aspergillus niger. Transformation probably occurred by non-homologous integration
      of the transforming vector into the chromosome. Co-transformation with the AMA 1
      replicating element from A. nidulans enhanced transformation frequency up to 2000
      fold, and was shown to result in autonomous maintenance of replicating
      concatenates, one of which was re-isolated by transformation of E. coli.

PMID- 8575024
TI  - Isolation, characterization and chromosomal mapping of an actin gene from the
      primitive red alga Cyanidioschyzon merolae.
AB  - Based on the results of cytological studies, it has been assumed that
      Cyanidioschyzon merolae does not contain actin genes. However, Southern
      hybridization of C. merolae cell-nuclear DNA with a yeast actin-gene probe has
      been suggested the presence of an actin gene in the C. merolae genome. In the
      present study, an actin gene was isolated from a C. merolae genomic library using
      a yeast actin-gene probe. The C. merolae actin gene has no intron. The predicted
      actin is composed of 377 amino acids and has an estimated molecular mass of 42
      003 Da. Southern hybridization indicated that the C. merolae genome contains only
      one actin gene. This gene is transcribed at a size of 2.4 kb. When Southern
      hybridization was performed with C. merolae chromosomes separated by pulsed-field
      gel electrophoresis, a band appeared on unseparated chromosomes XI and XII. A
      phylogenetic tree based on known eucaryote actin-gene sequences revealed that C.
      merolae diverged after the division of Protozoa, but before the division of
      Fungi, Animalia and Chlorophyta.

PMID- 8575023
TI  - Primary structure and expression pattern of the 33-kDa chitinase gene from the
      mycoparasitic fungus Trichoderma harzianum.
AB  - A gene (chit33) from the mycoparasitic fungus Trichoderma harzianum, coding for a
      chitinase of 33 kDa, has been isolated and characterized. Partial amino-acid
      sequences from the purified 33-kDa chitinase were obtained. The amino-terminal
      peptide sequence was employed to design an oligonucleotide probe and was used as
      a primer to isolate a 1.2-kb cDNA. The cDNA codes for a protein of 321 amino
      acids, which includes a putative signal peptide of 19 amino acids. All
      microsequenced peptides found in this sequence, indicate that this cDNA codes for
      the 33-kDa chitinase. A high homology (approximately 43% identity) was found with
      fungal and plant chitinases, including yeast chitinases. However enzyme
      characteristics suggest a nutritional (saprophytic or mycoparasitic), rather than
      a morphogenetic, role for this chitinase. The chit33 gene appears as a single
      copy in the T. harzianum genome, is strongly suppressed by glucose, and de
      repressed under starvation conditions as well as in the presence of autoclaved
      mycelia and/or fungal cell walls. The 33-kDa chitinase seems to be very stable
      except under starvation conditions. The independent regulation of each of the
      chitinases in T. harzianum indicates different specific roles.

PMID- 8575025
TI  - Phylogeny of Alternaria fungi known to produce host-specific toxins on the basis
      of variation in internal transcribed spacers of ribosomal DNA.
AB  - The internal transcribed spacer regions (ITS1 and ITS2) of ribosomal DNA from
      Alternaria species, including seven fungi known to produce host-specific toxins,
      were analyzed by polymerase chain reaction-amplification and direct sequencing.
      Phylogenetic analysis of the sequence data by the Neighbor-joining method showed
      that the seven toxin-producing fungi belong to a monophyletic group together with
      A. alternata. In contract, A. dianthi, A. panax, A. dauci, A. bataticola, A.
      porri, A. sesami and A. solani, species that can be morphologically distinguished
      from A. alternata, could be clearly separated from A. alternata by phylogenetic
      of the ITS variation. These results suggest that Alternaria pathogens which
      produce host-specific toxins are pathogenic variants within a single variable
      species, A. alternata.

PMID- 8575026
TI  - New alleles of mgm1: a gene encoding a protein with a GTP-binding domain related
      to dynamin.
AB  - Three previously described genes that affect baker's yeast (Saccharomyces
      cerevisiae) mitochondrial DNA (mtDNA) or mitochondrial RNA, tpm2-1, mna1-1, and
      mgm-1-1, are shown to be alleles of the same gene. This report demonstrates that
      tpm2-1 does not affect recombination of mtDNA. Therefore, there is no evidence
      that this dynamin-like protein is involved in movement of mtDNA within a cell.

PMID- 8575027
TI  - Studies on the minor constituents of the Caribbean gorgonian octocoral Briareum
      asbestinum Pallas. Isolation and structure determination of the eunicellin-based
      diterpenoids briarellins E--I.
AB  - Five new eunicellin-type diterpenoids, briarellins E--I, along with several known
      diterpenoids of the asbestinane, briarane and eunicellane classes, were isolated
      from the Caribbean gorgonian octocoral Briareum asbestinum collected in Puerto
      Rico. The structures of these compounds were established on the basis of
      spectroscopic evidence.

PMID- 8575028
TI  - Medicinal foodstuffs. I. Hypoglycemic constituents from a garnish foodstuff
      "taranome," the young shoot of Aralia elata SEEM.: elatosides G, H, I, J, and K.
AB  - Five new saponins named elatosides G, H, I, J, and K were isolated from a garnish
      foodstuff "Taranome," the young shoot of Aralia elata SEEM., together with
      hederagenin-3-O-glucuronopyranoside and elatoside C. Their chemical structures
      were elucidated on the basis of chemical and physicochemical evidence. Elatosides
      G, H, and I were found to exhibit potent hypoglycemic activity in the oral
      glucose tolerance test in rats.

PMID- 8575029
TI  - Synthesis and structure-activity relationships of gelatinase inhibitors derived
      from matlystatins.
AB  - To investigate a series of new inhibitors of gelatinases based on matlystatin B
      (1b), extensive structure-activity relationship studies were performed. The new
      derivatives were evaluated in vitro for the ability to inhibit gelatinases. The
      inhibitory activities against thermolysin were also assayed to test the
      compounds' selectivity. Among the compounds modified at the P'3 moiety, the N
      methylamide derivative 5 g was virtually twice as effective on gelatinase B as
      the parent compound 1b (5g, IC50 = 0.27 microM vs. 1b, IC50 = 0.57 microM). Other
      derivatives, including 1) esters 7a and 7b having the ester portions P'2 and P'3,
      2) the cyclic amino acids, L-proline or L-pipecolinic acid (13a and 13b) bearing
      P'2, and 3) compounds 29a and 29b representing an attachment of the pentyl side
      chain at C3' (P'1 side chain) instead of C2', all showed decreased potencies. The
      key discovery was the observation that the introduction of a nonyl group at the
      P'1 position yielded a compound (31f, IC50 = 0.0012 microM) with high inhibitory
      activity against gelatinases and high selectivity over thermolysin. This result
      suggested that the S'1 subsites of the gelatinases have a locally deep
      hydrophobic structure, since on the basis of the optimum inhibitory activity in
      the alkyl series, the nonyl group seems to fit best into this hydrophobic pocket.
      Thus 31f exhibited a 475-fold more potent inhibitory activity than 1b towards
      gelatinase B.

PMID- 8575030
TI  - Preparation and biological activity of 24-epi-26,26,26,27,27,27-hexafluoro- 1
      alpha,25-dihydroxyvitamin D2.
AB  - A new fluorinated analog of vitamin D2, 24-epi-26,26,26,27,27,27-hexafluoro- 1
      alpha,25-dihydroxyvitamin D2, was efficiently synthesized starting from (R)-4
      isopropyl-3-propionyl-2- oxazolidinone with high stereochemical control. In all
      four physiological test systems, the fluorinate vitamin D2 analog was found to be
      slightly less active than 1 alpha,25-dihydroxyvitamin D3.

PMID- 8575031
TI  - Generation of polyclonal catalytic antibodies against cocaine using transition
      state analogs of cocaine conjugated to diphtheria toxoid.
AB  - Six novel transition state analogs (TSAs) of cocaine (10-14 and 17) and one non
      cocaine, p-aminophenylphosphonyl ester of cyclohexanol (19), were synthesized and
      characterized by 1H- and 13C-NMR and FAB-MS. (1R)-ecgonine methyl ester or
      cyclohexanol were subjected to phenylphosphonylation in the presence of
      dicyclohexyl carbodiimde (DCC) and 4-N,N-dimethyl aminopyridine (4-DMAP). TSA-IV
      (10), however, was synthesized from norcocaine which was protected with
      dibromoethane to yield 4 before acid hydrolysis, esterification and
      phenylphosphonylation were carried out. TSA-III (11) TSA-I (12) and (19), using
      various length spacer arms, were coupled with the immunogenic protein, diphtheria
      toxoid (DT). The TSAs coupled with DT were used to immunize mice and after
      appropriate boosts their sera were tested for the presence and titer of anti-TSA
      polyclonal antibodies using ELISA. Preliminary results show that the mice
      immunized with these TSAs produced high titers of polyclonal catalytic
      antibodies, except for (19), with the ability to hydrolyze the substrate 125I-4'
      iodococaine in an in vitro assay, even in the presence of noncatalytic anti-TSA
      antibodies.

PMID- 8575032
TI  - Development of potent serotonin-3 (5-HT3) receptor antagonists. II. Structrue
      activity relationships of N-(1-benzyl-4-methylhexahydro-1H-1,4- diazepin-6
      yl)carboxamides.
AB  - Our studies on 4-amino-5-chloro-2-ethoxybenzamides led to the discovery that the
      N-(1,4-dimethylhexahydro-1H-1,4-diazepin-6-yl)benzamide 9 and the 1-benzyl-4
      methylhexahydro-1H-1,4-diazepine analogue 10 are potent serotonin-3 (5-HT3)
      receptor antagonists. Structure-activity relationship (SAR) studies on the
      influence of the aromatic nucleus of 9 and 10 upon inhibition of the von Bezold
      Jarisch reflex in rats are described. Heteroaromatic rings such as pyrrole,
      thiophene, furan, pyridine, pyridazine, 1,2-benzisoxazole, indole, quinoline, and
      isoquinoline rings showed weak 5-HT3 receptor antagonistic activity. Within this
      series, use of the 1H-indazole ring as an aromatic moiety led to a substantial
      increase of the activity; the 1H-indazolylcarboxamides 54, 57, 97, and 102 showed
      potent 5-HT3 receptor antagonistic activity. The optimal compound identified via
      extensive SAR studies was N-(1-benzyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-1H
      indaz ole-3- carboxamide (54), whose effect was superior to that of the
      corresponding benzamide 10 and essentially equipotent to those of ondanbsetron
      (1) and granisetron (4).

PMID- 8575033
TI  - Synthesis of carboxymethylpullulan-peptide-doxorubicin conjugates and their
      properties.
AB  - The amino group of doxorubicin (DXR) was found to be bound to the carboxyl group
      of carboxymethylpullulan (CMPul) either directly or through tetrapeptide spacers,
      including Gly-Gly-Phe-Gly, Gly-Phe-Gly-Gly and Gly-Gly-Gly-Gly. These conjugates
      had DXR contents of 6.1-7.1%, with the degree of substitution of carboxymethyl
      groups being 0.6 per sugar moiety. These conjugates associate in phosphate
      buffered saline (PBS) (pH 7.4), forming micelles with hydrophobic DXR inside and
      hydrophilic CMPul on the outside. The amounts of DXR released from the conjugates
      in the presence of rat liver lysosomal enzymes were determined by HPLC. The rate
      of the drug release differed among the conjugates tested. CMPul-DXR conjugate
      bound through Gly-Gly-Phe-Gly released 35% of its DXR over 24 h. On the other
      hand, CMPul-DXR conjugate without spacer released no free DXR. The antitumor
      effect of each conjugate in rats bearing Walker 256 was studied by monitoring the
      tumor weights after a single intravenous injection. Compared with DXR, CMPul-DXR
      conjugates bound through Gly-Gly-Phe-Gly and Gly-Phe-Gly-Gly spacers
      significantly suppressed the tumor growth, while CMPul-DXR conjugate bound
      through Gly-Gly-Gly-Gly showed less antitumor effect than DXR. CMPul-DXR
      conjugate bound through Gly-Gly-Gly-Gly showed less antitumor effect than DXR.
      CMPul-DXR conjugate without spacer showed no in vivo antitumor effect even at a
      dose equivalent to as much as 20 mg/kg of DXR.

PMID- 8575034
TI  - In vitro dissolution tests corresponding to the in vivo dissolution of
      clarithromycin tablets in the stomach and intestine.
AB  - The correlation between in vivo and in vitro dissolution of clarithromycin (CAM)
      tablets was examined. In vivo dissolution rate constants in the stomach and the
      intestine were obtained from analysis of the urinary excretion data of CAM
      following oral administration to humans in the fasting or postprandial state
      using a pharmacokinetic model including gastrointestinal transit. In the present
      study, the flow-through cell method with moderate agitation was used, as the in
      vitro dissolution test related to the in vivo dissolution rate constants. Both
      the effects of pH of the dissolution medium and the volumetric solvent flow rate
      on the dissolution rate in the flow-through cell method were examined. The pH of
      the dissolution medium and the flow rate were related to the in vitro dissolution
      rate. Therefore, the conditions of the flow-through cell method in correlation
      with the in vivo dissolution rates in the stomach and intestine were determined
      by controlling the flow rate at pH 3.0 and 6.8 dissolution medium. The urinary
      excretion of CAM, simulated by substituting the in vitro dissolution rate
      constants into the equation, were consistent with the in vivo data. The in vitro
      tests corresponding to the in vivo dissolution in the stomach and intestine
      following a single oral administration in the fasting or postprandial state for a
      CAM tablet were established.

PMID- 8575035
TI  - Study of the interaction between xylazine and bovine serum albumin by
      fluorescence quenching measurements.
AB  - The binding of xylazine to bovine werum albumin (BSA) was studied by fluoresence
      quenching, as a function of temperature. The experimental data could be fitted to
      both the Stern-Volmer equation and the Stern-Volmer equation modified by Lehrer.
      The temperature dependence of the Stern-Volmer constant, Ksv suggests that the
      mechanism of the quenching process is mainly dynamic in origin. The thermodynamic
      parameters were estimated based on such temperature dependence. The positive
      values found for the enthalpy and entropy changes seem to indicate that the
      hydrophobic contribution is the predominant intermolecular force stabilizing the
      xylazine-BSA complex. Fluorescence quenching was also used to calculate the
      binding constants by the Scatchard procedure. The values of these constants are
      of the same order of magnitude as the Stern-Volmer constants. These results,
      together with the spectral changes in the fluorescence emission spectra of BSA
      induced by xylazine, suggest that the interaction may take place in subdomains
      IIA and IIIA since these subdomains have been proposed to bind drugs and other
      hydrophobic materials.

PMID- 8575036
TI  - Studies on antiulcer agents. III. Plausible mechanism of antisecretory action of
      ethyl 2[(1H-benzimadazol-2-yl)sulfinylmethyl]-4-dimethylamino- 5
      pyrimidinecarboxylate, an H+/K(+)-ATPase inhibitor, based on its reaction with
      thiols.
AB  - To explore the mechanism of the gastric antisecretion activity of ethyl 2-[(1H
      benzimidazol-2-yl)sulfinylmethyl]- 4-dimethylamino-5-pyrimidinecarboxylate (5), a
      potential H+/K(+)-ATPase inhibitor, in the acid compartment of parietal cells,
      its reaction with some alkylthiols in the presence of hydrochloric acid was
      investigated. Upon treatment with 2-mercaptoethanol under acidic conditions, 5
      gave a characteristic 1:2 adduct, ethyl 4-[2-(2-hydroxyethyldithio)- 1-(2
      hydroxyethylthio)ethylidenamino]pyrimido[1,2-a]benzimid azole-3- carboxylate (6),
      instead of providing a disulfide of type 3, 2-(2
      alkyldithiomethylpyridino)benzimidazolide, the product predicted to be formed
      according to the reaction mechanism of common H+/K(+)-ATPase inhibitors, such as
      omeprazole or lansoprazole, with mercaptans. With a large excess of 2
      mercaptoethanol, 5 provided 2-(2-hydroxyethylthio)-1H-benzimidazole (8) and ethyl
      4-dimethylamino-2-(2-hydroxyethyldithio)-5-pyrimidinecarboxylat e (9) as well as
      6. The transformation mechanisms and their implications are discussed.

PMID- 8575037
TI  - Synthetic nucleosides and nucleotides. XXXV. Synthesis and biological evaluations
      of 5-fluoropyrimidine nucleosides and nucleotides of 3-deoxy-beta-D-ribofuranose
      and related compounds.
AB  - 1-O-Acetyl-2,5-di-O-p-chlorobenzoyl-3-deoxy-D-ribofuranose (1), derived from the
      antibiotic cordycepin was coupled with trimethylsilylated derivatives (2a-c) of
      N4-propionylcytosine, N4-p-toluoyl-5-fluorocytosine and 5-fluorouracil in the
      presence of trimethylsilyl trifluoromethanesulfonate (TMS-triflate) to give fully
      acylated nucleosides (3a-b and 3d, respectively). Selective removal of the N4
      propionyl group of 3a by treatment with hydrazine hydrate gave 2',5'-di-O-p
      chlorobenzoyl-3'-deoxycytidine (4). Deamination of 4 with sodium nitrite in
      trifluoroacetic acid afforded 2',5'-di-O-p-chlorobenzoyluridine (3c) in good
      yield. Compounds 3a-d were saponified to give free 3'-deoxycytidine (5a), 5
      fluoro-3'-deoxycytidine (5b), 3'-deoxyuridine (5c), and 5-fluoro-3'-deoxyuridine
      (5d), respectively. These 3'-deoxyribonucleosides (5a-d) were then converted to
      corresponding 5'-monophosphate and further phosphorylated to the 5'-triphosphates
      by the phosphoroimidazolidate method. The nucleosides (5a-d) were examined for
      growth-inhibitory effects on mouse leukemic L5178Y cells, and their IC50 values
      (microgram/ml) were 1.8, 33, 6.5, and 18, respectively. On the other hand, the
      antiviral activities of these compounds on a rhabdovirus, infectious
      hematopoietic necrosis virus (IHNV), were moderate (IC50 = 100-500 micrograms/ml
      in CHSE-214 cells). The 5'-triphosphates showed remarkable inhibitory effects on
      DNA polymerase beta and DNA polymerase alpha-primase purified from testes of the
      cherry salmon, Oncorhynchus masou, but not on common DNA polymerase alpha from
      same source.

PMID- 8575038
TI  - Quantitative relation between surface active properties and antibiotic activity
      of 1-alkyl-3-alkylthiomethylimidazolium chlorides.
AB  - The critical micelle concentration (CMC) values were determined by surface
      tensiometry, and the hydrophobicity index (HI) was calculated. The quantitative
      relation between the minimum inhibitory concentration (MIC) and the CMC, and the
      HI was calculated.

PMID- 8575040
TI  - Preparation of characteristic diagram for refolding of lysozyme.
AB  - The characteristic diagram for refolding of denatured reduced lysozyme was
      prepared in terms of recovered activity by employing urea and LiCl concentrations
      as two axes of rectangular coordinates. The diagram obtained will serve as a new
      tool not only for the optimum design of refolding media but also for the study of
      the refolding mechanism.

PMID- 8575039
TI  - Studies on antiulcer agents. IV. Antiulcer effects of 2-benzylthio5,6,7,8
      tetrahydro-4(3H)-quinazolinones and related compounds.
AB  - With a view to finding more effective antiulcer agents, a series of 2-benzylthio
      5,6,7,8-tetrahydro-4(3H)-quinazolinones and related compounds were synthesized
      and evaluated in a histamine-stimulated gastric secretion model. The sodium salt
      of the 2-(dimethylamino)benzylthio derivative (8) showed gastric mucosal
      protection and gastric antisecretion activities, and was also effective against
      experimental gastric and duodenal ulcers induced by some ulcerogenic agents.
      Based on a comparison of the antiulcer properties of 8 with those of the lead
      compounds (1 and 2) and cimetidine, it appears that, for improvement of antiulcer
      activity, the reduction of gastric acidity is a more important factor than the
      reduction of gastric volume output or gastric total acid output.

PMID- 8575041
TI  - The absolute structures of new 1 beta-hydroxysacculatane-type diterpenoids with
      piscicidal activity from the liverwort Pellia endiviifolia.

PMID- 8575042
TI  - Camelliatannin D, a new inhibitor of bone resorption, from Camellia japonica.
AB  - Camelliatannin D (1), a new complex tannin which inhibits Ca release from mouse
      calvaria, was isolated from the leaves and fruits of Camellia japonica L.
      (Theaceae). This tannin is the first example of complex tannin composed of a
      dimeric hydrolyzable tannin and a flavan-3-ol.

PMID- 8575043
TI  - [Studies on the transcription regulation by upstream sequence of human heat shock
      protein 90 beta gene].
AB  - Using a pair of synthetic oligonucleotide as primers, human peripheral lymphocyte
      lambda GEM-11 genomic DNA library as template, a fragment spanning -1102/+68bp of
      human heat shock protein 90 beta gene was amplified by polymerase chain reaction
      (PCR) and cloned into pGEM-4Z vector. The cloned fragment was truncated and
      ligated to an eukaryotic expression vector containing luciferase as a reporter
      gene. These subclones were transfected into Jurkat cells and the cellular
      luciferase activity and mRNA level were measured under either heat shock or PHA
      activation. Our results suggest that: (1) 5' flanking sequences of hsp90 beta
      mediates a relatively higher basal level expression via promotor region; (2)
      under heat shock, presence of the fragment surprisingly reduced luciferase
      activity, a heat shock induced negative regulatory element was restricted to 
      554/-171bp; and (3) PHA activation requires distal 5' sequence.

PMID- 8575044
TI  - [Construction and expression of the gene CD4V1V2-PE40, coding for a molecular
      targeted protein against AIDS].
AB  - We here replaced the cell-binding domain in Pseudomonas exotoxin A (PE) with HIV
      binding portion of CD4V1V2 molecule and constructed a chimeric gene CD4V1V2-PE40,
      which can be expressed in E. coli. The hybrid protein displays targeting toxicity
      toward cells infected by HIV and thus represents a promising novel therapeutic
      agent for the treatment of AIDS.

PMID- 8575045
TI  - [Anisodamine (654-2) improves impaired cognitive function induced by experimental
      brain damage].
AB  - Surgery of brain injury was established in rats with medial frontal cortex lesion
      or acute cerebral ischemia and reperfusion. Learning and memory deficits were
      induced. These rats can be served as the animal model of dementia.
      Intraperitoneal injection of 654-2 (30 mg/kg per day) started from the day of
      surgery until a total of 10 shots were given. We first reported that 654-2
      improved the deficits of learning and memory in avoidance response of rats after
      the two types of brain damage. Further more, the results showed that 654-2
      enhanced SOD activity and inhibited the elevation of superoxides (MDA) in
      forebrain of cortex-lesioned rats. results suggest that 654-2 probably has the
      effect of protection of the brain cell against the injury of free radicals.

PMID- 8575046
TI  - [Vasoactive intestinal polypeptide prevents injury of pulmonary vascular
      permeability due to xanthine with xanthine oxidase].
AB  - Hyperpermeability is the crux of pathogenesis of sudden lung edema in many
      pulmonary disorders, especially in acute lung injury and acute respiratory
      distress syndrome (ARDS). Using our modified method for assessment of pulmonary
      vascular permeability, we observed the effects of xanthine with xanthine oxidase
      (X-XO) perfused in rat pulmonary artery and the protection of vasoactive
      intestinal polypeptide (VIP) against the injury of pulmonary vascular
      permeability. After addition of xanthine oxidase in the perfusate reservoir
      containing xanthine, 125I-albumin leak index (125I-ALI) was remarkably increased
      while peak airway pressure (Paw) showed no significant increase, and perfusion
      pressure of pulmonary artery (Ppa) and lung wet/dry weight ratio (W/D) were only
      slightly increased. Xanthine plus xanthine oxidase also increased thromboxane B2
      (TX B2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in the perfusate.
      Treatment with VIP obviously reduced or totally prevented all signs of injury.
      Simultaneously, VIP also diminished or abolished the associated generation of
      arachidonate products. The results indicated that VIP has potent protective
      activity against injury of pulmonary vascular permeability and may be a
      physiological modulator of inflammatory damage to vascular endothelium associated
      with toxic oxygen metabolites.

PMID- 8575047
TI  - [Quantitative study of a SEM image processing system on the absorptive
      mesothelium of the diaphragmatic peritoneum].
AB  - SEM and a medical image processing system attached to SEM were used to study the
      peritoneal mesothelium on mice diaphragm. The absorptive mesothelium was first
      reported owing to its function and morphology. The absorptivity of diaphragmatic
      peritoneum was surveyed by the measurement of the area of the absorptive
      mesothelium. The arrangement of the absorptive mesothelium on diaphragmatic
      peritoneum was block-like with abnormal distribution, and the maximum and minimum
      areas of the block were 1153 microns 2 and 66 microns 2. But the absorptive
      mesothelium on left and right half diaphragm were normally distributed. The
      average areas of the absorptive mesothelium on all diaphragm, left half diaphragm
      and right half diaphragm were 432.6 microns 2, 270.5 microns 2 and 512.0 microns
      2 respectively. The distributive law of the absorptive mesothelium was costal
      portion > sternum portion > vertebral column portion. The average absorptivity of
      all diaphragmatic peritoneum was 29.2%, but that of left and right half
      diaphragmatic peritoneum were 17.4% and 32.9% respectively.

PMID- 8575048
TI  - [The role of substance P in immunosuppression induced by Tripterygium wilfordii].
AB  - The effects of T II (extracted from Tripterygium wilfordii) and substance P (SP)
      on imunoregulation were investigated. It has been shown that Tripterygium
      wilfordii is an immunosuppresive. In order to assess the immunosuppression
      elicited by T II was mediated by SP in spinal dorsal horn, Wistar rats were
      injected intrathecally with capsaicin (CAP) to deplete SP in spinal dorsal horn
      prior to T II given orally. The level of interleukin 2 (IL-2) produced by splenic
      lymphocytes of rats and the contents of SP in some brain areas and spinal cord in
      mice were assayed after T II treatment. Our findings were as follows: 1. The
      level of IL-2 was decreased significantly after T II treatment only. However the
      level of IL-2 was increased markedly after CAP was given intrathecally. Moreover,
      CAP administration also enhanced the level of IL-2 even in immunosuppression
      group induced by T II treatment. 2. SP contents in spinal cord, hypothalamus and
      brain stem of mice were increased dramatically during immunosuppression produced
      by T II. The results suggested that SP in spinal dorsal horn was involved in
      regulation of cellular immunity, the suppressive effect of T II on cellular
      immunity might be mediated by SP in spinal dorsal horn.

PMID- 8575049
TI  - [Interleukin-2 gene cloning and expression in S. cerevisiae].
AB  - Mature human Interleukin-2 gene was amplified from IL-2 cDNA by PCR methods. The
      PCR product was cloned into pUC12 plasmid at Sma I site, then precisely
      engineered into an intermidiate vector pSK43SB which were digested with Hind III,
      mung bean nuclease, and Sal I. Added BamH I linker to Cla I site of pSK43SB-IL2
      to produce one more BamH I site, then digested pSK43DB-IL2 with restriction
      enzyme BamH I, the BamH I fragment with an alpha-factor leading sequence, IL2
      gene and cycl terminater were produced. It was then cloned into a typical high
      efficiency episomal expression vector YEpHc8. Human IL-2 protein was purified
      from supernatant secreted by yeast transformants of YEpHc8-IL2 leading by alpha
      factor promoter with IL-2 right translational reading frame and accurate cleavage
      site. High level expression of IL-2 with highly activity has been purified. A
      sugar specific silver staining method and 3H sugar labelling experiment has shown
      the detection of carbohydrate component.

PMID- 8575050
TI  - [Proto-oncogene point mutation of c-Ha-ras in bronchogenic carcinoma].
AB  - 11 bronchogenic carcinoma and 8 corresponding paracarcinoma specimens were
      detected for activating point mutation in codon 12 of c-Ha-ras gene by Southern
      blotting hybridization technique. The c-Ha-ras gene was found to be activated by
      point mutation in codon 12 in 8 of bronchogenic carcinoma and 1 of paracarcinoma
      tissues. The mutative and unmutative hybrid band was both discovered in 2 of
      paracarcinoma tissues. Analysis of clinical and pathological features, we
      conclude that: (1) The point mutation of c-Ha-ras gene codon 12 is found in 77.8%
      bronchogenic carcinoma among Chinese; (2) At least in part cases, mutation of c
      Ha-ras gene codon 12 is not the "initiation" event, but may be a early-stage
      event in the pathogenesis; (3) No apparent association between the c-Ha-ras gene
      codon 12 mutation and pathological types, disease stages and history of smoking
      is present.

PMID- 8575051
TI  - [Intra- and extra-cranial arterial lesions in TIA patients].
AB  - Ninety-six patients with transient ischemia attacks were examined by transcranial
      Doppler (TCD), carotid color-coded ultrasonic imagine, brain computed tomographic
      scan (CT), compared with digital subtract angiography (DSA), MRI and MRA were
      done in some cases. The abnormality of CT and MRI was 30.2% and 74.1%,
      respectively. The most common findings were lacunar infarction or cerebral
      atrophy. Sixty-two cases fulfilled the TCD criteria of definitive arterial
      stenosis (64.5%) and three cases of arteriovenous malformation, among whom 27
      patients (43.5%) carried out the examination of DSA. There was an excellent
      coincidence between the DSA and TCD findings, although DSA showed more vessels
      involved in some patients. Of the 96 cases, the intracranial arterial stenosis or
      occlusion was in 48.5% and the extracranial in 17.8%. The younger patients (age <
      60 years) were subject to involvement of unilateral intracranial artery, but the
      older had predominantly the bilateral intracranial arterial and extracranial
      carotid or subclavian arterial lesions.

PMID- 8575052
TI  - [Risk factors for Guillain-Barre syndrome in northern China: a case-control
      study].
AB  - We conducted a case-control study in northern China to estimate possible risk
      factors for Guillain-Barre Syndrome (GBS). Forty patients were consecutively seen
      at the PUMC hospital and the Second Hospital of Hebei Medical College between
      July and September 1991. The diagnosis was established following the NINCDS
      criteria for GBS. Among 36 patients with measurements of motor evoked potentials,
      34 had evidences of demyelination. Eighty controls chosen from spouses or
      siblings, and neighbors or work/school mates, were matched by sex and age (+/- 3
      years). Using the Mantel-Haenszel estimate of the odds ratio, cold rain,
      overloaded activities, a history of diarrhea, common cold, and exposure to
      organophosphorus one month before onset, significantly increased, at least six
      fold, the risk for development of GBS. Cases and controls did not differ in the
      number of previous vaccinations. We suggest that a single antigent is less likely
      of etiological importance in GBS.

PMID- 8575053
TI  - [Comparison among several 99mTc antibody-labeling methods].

PMID- 8575054
TI  - [Clinical research of muscular relaxation induced by alcuronium and pancuronium].
AB  - The clinical experiment was designed for observing effect of muscular relaxation
      induced by alcuronium and pancuronium. 40 patients were randomly divided into
      alcuronium group (A) and Pancuronium group (P). A group and P group were
      redivided into A1,A2 groups and P1,P2 groups according to differences of the
      initial doses of muscle relaxants. The results of neuromuscular monitoring
      indicate that onset time and main-tenance time of 0.3 mg/kg alcuronium were
      respectively 2.4 min and 63 min; 0.1 mg/kg pancuronium were 2.7 min and 70 min.
      The initial doses mentioned above are suitable to intubation of anesthesia and
      meet surgical need for muscular relaxation. The changes of MAP,HR,blood kalium
      and natrium were not evident in statistical significance before and after
      administration of relaxants.

PMID- 8575055
TI  - [Clinical study of sperm intro-fallopian transfer].
AB  - To explore the new technique of assistant pregnancy, we transferred sperm into
      fallopian tubes by laparoscopy Via an operation named sperm intra-fallopian
      transfer (SIFT). Twenty-nine infertile women (eighteen patients in natural
      menstrual cycle group, the others in the group of stimulated ovulation cycle) had
      their fallicle development with B ultrasonic scanning monitored. Patients were
      examined by laparoscopy before ovulation, then prepared sperm was transferred
      into fallopian tubes. Amony twenty-nine patients who had SIFT, three were
      pregnant in the operation month. The rate of pregnancy in operation month was 10.
      3%, The rate of pregnancy during six months after SIFT was 31.0% (9 cases). Amony
      fifteen patients with "real" unexplained infertility, the rate of pregnancy
      during six months after SIFT was 46.7%. This preliminary result, showed that on
      the basis of skilled technique of laparoscopy, SIFT is a new, simple, safe,
      economic and effective method in treating infertility.

PMID- 8575056
TI  - [Karyotype analysis of Candida species by PFGE and its use in classicification].
AB  - Electrophoretic karyotype in 7 medically important Candida species was analyzed
      by pulsed-field gel electrophoresis. The chromosomal DNAs of the Candida species
      were separated into 4-10 bamds ranging in size from 0.5-2.8 Mb. These patterns
      were species-specific, so the electrophoretic karyotype can be used as a genotype
      basis for classification and identification of Candida species.

PMID- 8575057
TI  - [Clinical observation of oral cefuroxime axetil for treating acute gonorrhoea].
AB  - The effectiveness of a single oral dose of Zinnat (cefuroxime axitil) in treating
      acute gonorrhoea was assessed in 12 men and 2 women who received 1.0 g. the cure
      rate was 85.7% (12/14). No adverse effect was found. Zinnat was effective,
      convenient, well tolerated and valuable drug in treatment of acute gonorrhoea.

PMID- 8575058
TI  - [Two case of androgen-secreting ovary tumor].
AB  - Two cases of androgen-secreting ovary tumor were reported. patients' chief
      complaints were menoxemia and hirsutism; clitorism was found by physical
      examination. Their serum testosterone (T) were high (10.2-6.7nmol/L) and could
      not be suppressed to normal range by middle-dose dexamethasone inhibiting test.
      ACTH stimulating test could not stimulate the high serum T to raise futher, but
      HCG stimulating test could increase serum T to higher level. Pelvic examination,
      type B ultrasonic and CT scan confirmed a mass on one of the ovaries. Sertoli
      Leydig cell tumor and gynandroblastoma were proved respectively by pathology.
      After removing the tumor, their serum T were returned to normal level.

PMID- 8575059
TI  - Transforming growth factor-beta signal transduction.

PMID- 8575060
TI  - Targeting of transgene expression to the vascular endothelium of mice by
      homologous recombination at the thrombomodulin locus.
AB  - We describe a straightforward gene-targeting technique to achieve uniform,
      stable, and genetically invariant expression of a transgene in the vascular
      endothelium of mice. To demonstrate the feasibility of this approach, the
      reporter gene bacterial beta-galactosidase was inserted via homologous
      recombination into the intronless thrombomodulin locus of murine embryonic stem
      cells. In this fashion, the lacZ gene is placed under the regulatory control of
      the endogenous thrombomodulin promoter. The expression of the transgene in adult
      mice recapitulated the widespread, stable, and high-level expression of the
      thrombomodulin gene in vascular endothelium. These data indicate that targeting
      of cDNAs into the thrombomodulin locus serves as a viable strategy to express
      transgenes in endothelial cells. Analysis of reporter gene expression revealed a
      heterogeneous pattern of thrombomodulin gene activity in the endothelium of the
      aorta and its tributaries. We also show that embryonic stem cells with a targeted
      thrombomodulin locus contribute in a mosaic fashion to the vascular endothelium
      of chimeric mice. This method for generating animals with a functionally
      heterogeneous cardiovascular system should provide an experimental technique for
      studying how localized genetic abnormalities in endothelial cell function lead to
      the development of vascular diseases.

PMID- 8575061
TI  - SM22 alpha, a marker of adult smooth muscle, is expressed in multiple myogenic
      lineages during embryogenesis.
AB  - SM22 alpha is a calponin-related protein that is expressed specifically in adult
      smooth muscle. To begin to define the mechanisms that regulate the establishment
      of the smooth muscle lineage, we analyzed the expression pattern of the SM22
      alpha gene during mouse embryogenesis. In situ hybridization demonstrated that
      SM22 alpha transcripts were first expressed in vascular smooth muscle cells at
      about embryonic day (E) 9.5 and thereafter continued to be expressed in all
      smooth muscle cells into adulthood. In contrast to its smooth muscle specificity
      in adult tissues, SM22 alpha was expressed transiently in the heart between E8.0
      and E12.5 and in skeletal muscle cells in the myotomal compartment of the somites
      between E9.5 and E12.5. The expression of SM22 alpha in smooth muscle cells, as
      well as early cardiac and skeletal muscle cells, suggests that there may be
      commonalities between the regulatory programs that direct muscle-specific gene
      expression in these three myogenic cell types.

PMID- 8575062
TI  - Myocyte enhancer binding factor-2 expression and activity in vascular smooth
      muscle cells. Association with the activated phenotype.
AB  - Proliferation and phenotypic modulation of smooth muscle cells (SMCs) are major
      components of the vessel's response to injury in experimental models of
      restenosis. Some of the growth factors involved in restenosis have been
      identified, but to date little is known about the transcription factors that
      ultimately regulate this process. We examined the expression of the four members
      of the myocyte enhancer binding factor-2 (MEF2) family of transcription factors
      in cultured rat aortic SMCs (RASMCs) and a rat model of restenosis because of
      their known importance in regulating the differentiated phenotype of skeletal and
      cardiac muscle. In skeletal and cardiac muscle, the MEF2s are believed to be
      important for activating the expression of contractile protein and other muscle
      specific genes. Therefore, we anticipated that the MEF2s would be expressed at
      high levels in medial SMCs that are producing contractile proteins and that they
      would be downregulated along with the contractile protein genes in neointimal
      SMCs. On the contrary, we observe that MEF2A, MEF2B, and MEF2D mRNAs are
      upregulated in the neointima, with the highest levels in the layer of cells
      nearest to the lumen, whereas MEF2C mRNA levels do not appreciably increase.
      Moreover, few cells in the media are making MEF2 proteins detectable by
      immunohistochemistry, whereas large numbers of neointimal cells are positive for
      all four MEF2s. These data suggest that the MEF2s are involved in the activated
      smooth muscle phenotype and not in the maintenance of contractile protein gene
      expression.

PMID- 8575063
TI  - Establishment of the mesodermal cell line QCE-6. A model system for cardiac cell
      differentiation.
AB  - The QCE-6 cell line was derived from precardiac mesoderm of the Japanese quail.
      As previously reported, these cells are able to differentiate into two distinct
      cardiac cell types with myocardial or endocardial endothelial cell properties.
      This present communication describes in detail the derivation of this cell line
      and further characterizes the nontreated and induced myocardial and endothelial
      phenotypes of these cells. The QCE-6 cells exhibit an epithelial morphology, as
      well as the pattern of protein expression, that is characteristic of precardiac
      mesoderm. Treatment with retinoic acid, basic fibroblast growth factor (bFGF),
      transforming growth factor (TGF)-beta 2, and TGF-beta 3 induces these cells to
      differentiate and produce mixed cultures of epithelial and mesenchymal cells. The
      epithelial cells express myosin, desmin, and cardiac troponin I in a punctate
      pattern throughout the cytoplasm. These sarcomeric proteins become organized in a
      premyofibrillar pattern when TGF-beta 1, platelet-derived growth factor (PDGF)
      BB, and insulin-like growth factor (IGF) II are added in combination along with
      retinoic acid, bFGF, TGF-beta 2, and TGF-beta 3. Also, these treatments induce
      Na+,K(+)-ATPase expression. When the QCE-6 cells are cultured on collagen type I,
      the mesenchymal cells that are promoted by retinoic acid, bFGF, TGF-beta 2, and
      TGF-beta 3 will invade the gel. These mesenchymal cells are positive for QH1 and
      JB3, which are both markers for presumptive endocardial cells within the early
      cardiogenic mesoderm. The addition of both PDGF-BB and IGF II to QCE-6 cell
      cultures will inhibit the ability of retinoic acid, bFGF, TGF-beta 2, and TGF
      beta 3 to induce both the mesenchymal morphology and QH1 and JB3 expression.
      Collectively, these results suggest that the proces of cardiac cell
      differentiation is regulated by multiple signals and that early cardiogenic
      mesoderm contains a bipotential stem cell that can give rise to both the
      myocardial and endocardial lineages. More important, since the QCE-6 cells are
      representative of early cardiogenic cells, this cell line offers a unique model
      system to study cardiac cell differentiation.

PMID- 8575064
TI  - Frequency-dependent activation of a constitutive nitric oxide synthase and
      regulation of contractile function in adult rat ventricular myocytes.
AB  - Cardiac myocytes have recently been shown to express a constitutive Ca(2+)
      sensitive isoform of NO synthase (NOS3), although the mechanism(s) responsible
      for activation of NOS3 and its physiological function remain to be determined.
      Since the activity of NOS3 is known to be regulated in part by the intracellular
      Ca2+ activity ([Ca2+]i) in endothelial cells, we determined whether increasing
      myocyte [Ca2+]i by uniform electric field pacing was accompanied by an increase
      in NOS3 activity, detected as nitrite accumulation in the medium. A higher
      [Ca2+]i with increasing pacing frequencies was shown to be accompanied by a time
      dependent accumulation of nitrite in medium that bathed adult rat ventricular
      myocytes stimulated at 3 Hz. Nitrite release by paced cells was significantly
      attenuated by treatment with either the NO synthase inhibitor nitro-L-arginine (L
      NA, 1 mmol/L) or the intracellular Ca2+ chelator BAPTA-AM (20 mumol/L). Paced
      myocytes also exhibited a frequency- and time-dependent increase in intracellular
      cGMP content that could be inhibited significantly by either L-NA or the soluble
      guanylate cyclase inhibitor LY83583 (5 mumol/L). To determine whether the
      increase in NOS3 activity with pacing affected contractile function, myocytes
      were sequentially paced at frequencies from 0.5 to 3 Hz. Methylene blue, L-NA,
      and LY83583 all increased the amplitude of shortening of myocytes paced at 3 Hz.
      Furthermore, a significantly greater positive inotropic response to high
      extracellular Ca2+ (3 mmol/L) was demonstrated by myocytes pretreated with L-NA
      compared with control cells. These data indicate that myocyte NOS3 activity is
      regulated in part by [Ca2+]i, whether induced by changes in pacing frequency or
      [Ca2+]o, and depresses myocyte contractile responsiveness to higher stimulation
      frequencies.

PMID- 8575065
TI  - Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle
      cells.
AB  - Augmentation of nitric oxide (NO) production in vivo decreases lesions in a
      variety of models of arterial injury, and inhibition of NO synthase exacerbates
      experimental intimal lesions. Both vascular smooth muscle cell (VSMC)
      proliferation and migration contribute to lesion formation. Although NO inhibits
      VSMC proliferation, its effects on VSMC migration are unknown. To test the
      hypothesis that NO inhibits VSMC migration independent of inhibition of
      proliferation, we examined migration of rat aortic VSMCs after wounding of a
      confluent culture in the presence of chemical donors of NO. Hydroxyurea was used
      to eliminate any confounding effect of NO on proliferation. Three NO donors,
      diethylamine NONOate, spermine NONOate, and S-nitrosoglutathione, exhibited
      concentration-dependent inhibition of both number of migrating VSMCs and maximal
      distance migrated. Inhibition of migration was also seen with 8-Br-cGMP,
      suggesting that activation of guanylate cyclase may play a role in mediating the
      antimigratory effects of NO. Migration resumed after removal of NO donors, as
      evidenced by an increase in distance migrated. Measurement of VSMC protein
      synthesis and mitochondrial respiration indicated that inhibition of migration by
      NO donors was not due to metabolic cytostasis. These findings indicate that NO
      reversibly inhibits VSMC migration independent of proliferation or cytotoxicity,
      a novel mechanism by which both endogenous and pharmacological NO may alter
      vascular pathology.

PMID- 8575066
TI  - Intestinal absorption of sodium and nitric oxide-dependent vasodilation interact
      to dominate resting vascular resistance.
AB  - The villi of the small intestine maintain a hypertonic interstitium at all times,
      and the submucosal glands constantly secrete ions and accompanying water into the
      lumen. Generation of the 400- to 600-mOsm interstitial fluid in the villus and
      secretion by glands may require a large expenditure of energy and, consequently,
      have major effects on intestinal vascular regulation to supply oxygen and
      nutrients. Blood flow and oxygen consumption were measured in the ileum of
      anesthetized rats during natural resting conditions with physiological sodium
      chloride in the bathing fluid and during isosmotic replacement of sodium chloride
      with mannitol. Microvascular pressures and blood flow were used to determine the
      changes in resistance of the major arterioles and the terminal vasculature. When
      mannitol replaced sodium chloride in contact with the villi, intestinal blood
      flow decreased to 58.6 +/- 2.8% of control, and oxygen consumption was 54.2 +/-
      3.4% of control. Resistance of the major arterioles increased 101.7 +/- 9.9%, and
      that of the terminal vasculature increased 40.4 +/- 6.2%. The increased
      resistance appeared to be caused by suppression of a nitric oxide mechanism.
      Local application of 10(-4) mol/L NG-nitro-L-arginine methyl ester caused about
      the same reduction in flow and increases in regional vascular resistance as
      during replacement of sodium but did not alter the oxygen consumption. These data
      indicate that about half of the intestinal metabolic rate during natural resting
      conditions is devoted to sodium secretion/absorption. Large resistance vessels
      are dilated to maintain a high blood flow through release of nitric oxide. We
      propose that dilation of the terminal vasculature in the metabolically active
      tissues increased flow velocity sufficiently in the major resistance vessels to
      cause a flow-mediated release of nitric oxide.

PMID- 8575067
TI  - Distribution and physiological roles of ATP-sensitive K+ channels in the
      vertebrobasilar system of the rabbit.
AB  - The effect of an opener (levcromakalim) and a blocker (glibenclamide) of ATP
      sensitive K+ (KATP) channels was investigated in the vertebrobasilar system of
      the rabbit. Arterial tension and membrane potential were measured by the
      isometric tension recording method and the microelectrode technique,
      respectively. Glibenclamide (10(-6) mol/L) depolarized the membrane and
      potentiated the contraction to histamine in vertebral arteries. The sensitivity
      to the relaxant effects of levcromakalim was in the following descending order:
      vertebral > proximal basilar > distal basilar > superior cerebellar arteries.
      Vertebral arteries were approximately 50 times more sensitive to levcromakalim
      than were superior cerebellar arteries. The relaxation to levcromakalim was
      abolished by glibenclamide (10(-6) mol/L). Glibenclamide attenuated
      vasorelaxation to adenosine in proximal arteries (vertebral and proximal basilar)
      but not in superior cerebellar arteries. Levcromakalim (7 x 10(-8) mol/L) and
      adenosine (10(-5) mol/L) induced glibenclamide-sensitive membrane
      hyperpolarization in vertebral arteries but not in distal basilar arteries. These
      results suggest that KATP channels contribute to the determination of resting
      membrane potential and resting tone in vertebral arteries. Furthermore, there is
      a marked heterogeneity in the sensitivity to an opener of KATP channels, and the
      heterogeneity has a functional link to the mechanism underlying vasorelaxation to
      adenosine in the vertebrobasilar system of the rabbit.

PMID- 8575068
TI  - Multiple domains contribute to the distinct inactivation properties of human
      heart and skeletal muscle Na+ channels.
AB  - Voltage-gated Na+ channels are essential for the normal electrical excitability
      of neuronal and striated muscle membranes. Distinct isoforms of the Na+ channel
      alpha-subunit have been identified by molecular cloning, and their functional
      attributes have been defined by heterologous expression coupled with
      electrophysiological recording. Two closely related Na+ channel alpha-subunit
      isoforms, hH1 (human heart) and hSkM1 (human skeletal muscle), exhibit
      differences in their inactivation properties and in their response to the
      coexpressed beta 1-subunit. To localize regions that contribute to inactivation
      and to beta 1-subunit response, we have exploited these functional differences by
      studying chimeric channels composed of segments from both hH1 and hSkM1. Chimeras
      in which one or more of the cytoplasmic interdomain regions (ID1-2, ID2-3, and
      ID3-4) were exchanged between hH1 and hSkM1 exhibit inactivation properties
      identical with the background channel isoform, suggesting that these regions are
      not sufficient to cause gating differences. In contrast, inactivation properties
      of chimeras composed of approximately equal halves of the two channel isoforms
      were intermediate between hH1 and hSkM1. Furthermore, the response to the
      coexpressed beta 1-subunit was dependent on structures located in the carboxy
      terminal half of the alpha-subunit, although domains D3, D4, and the carboxy
      terminal are not singularly responsible for this effect. These data indicate that
      inactivation differences between hH1 and hSkM1 are determined by multiple alpha
      subunit domains.

PMID- 8575069
TI  - Interaction of cytotoxic T lymphocytes and guinea pig ventricular myocytes.
      Pharmacological modulation by blocking K+ currents in cytotoxic T lymphocytes.
AB  - Infiltrating cytotoxic T lymphocytes (CTLs) are important immune effectors that
      damage the myocardium during heart transplant rejection as well as in
      cardiomyopathy and Chagas' heart disease. We have previously shown that in an in
      vitro model of murine-derived peritoneal exudate CTL (PEL)-guinea pig ventricular
      myocyte interaction, PEL induced in conjugated myocytes reduction of resting
      membrane potential and action potential (AP) amplitude, shortening of AP
      duration, delayed afterdepolarizations (DADs), and myocyte contracture and
      destruction. Since these findings indicated that cytotoxicity was largely caused
      by [Ca2+]i overload, in the present study we tested the hypothesis that blocking
      the L-type Ca2+ current (ICa,L) in the myocyte will eliminate the trigger for
      Ca2+ release from intracellular stores and will reduce [Ca2+]i overload and
      subsequent myocyte deterioration. CoCl2 (3 mmol/L) prevented PEL-induced AP
      changes, induction of DADs, and myocyte destruction. Since verapamil (2 mumol/L)
      was ineffective, indicating that the CoCl2 protection was not due to block of
      ICa,L, we tested whether the different action of these Ca2+ channel blockers was
      due to their differential effect on the PEL's K+ current (IK), previously shown
      to participate in lymphocyte activation and cytotoxicity. In agreement with their
      protective efficacy, CoCl2 but not verapamil blocked IK in PELs, suggesting that
      this is the mechanism for the protection provided by CoCl2. To support this
      notion, we tested the effect of the scorpion-derived peptide margatoxin (10
      nmol/L), a specific K+ channel blocker in lymphocytes, on PEL-myocyte interaction
      and on PEL's IK; margatoxin prevented PEL-induced cytotoxicity and also blocked
      IK in PEL. Based on these findings, an alternative modality for attenuating CTL
      induced lymphocytotoxicity is proposed.

PMID- 8575070
TI  - Ionic mechanism of action potential prolongation in ventricular myocytes from
      dogs with pacing-induced heart failure.
AB  - Membrane current abnormalities have been described in human heart failure. To
      determine whether similar current changes are observed in a large animal model of
      heart failure, we studied dogs with pacing-induced cardiomyopathy. Myocytes
      isolated from the midmyocardium of 13 dogs with heart failure induced by 3 to 4
      weeks of rapid ventricular pacing and from 16 nonpaced control dogs did not
      differ in cell surface area or resting membrane potential. Nevertheless, action
      potential duration (APD) was significantly prolonged in myocytes isolated from
      failing ventricles (APD at 90% repolarization, 1097 +/- 73 milliseconds [failing
      hearts, n = 30] versus 842 +/- 56 milliseconds [control hearts, n = 25]; P <
      .05), and the prominent repolarizing notch in phase 1 was dramatically
      attenuated. Basal L-type Ca2+ current and whole-cell Na+ current did not differ
      in cells from failing and from control hearts, but significant differences in K+
      currents were observed. The density of the inward rectifier K+ current (IKl) was
      reduced in cells from failing hearts at test potentials below -90 mV (at -150 mV,
      -19.1 +/- 2.2 pA/pF [failing hearts, n = 18] versus -32.2 +/- 5.1 pA/pF [control
      hearts, n = 15]; P < .05). The small outward current component of IKl was also
      reduced in cells from failing hearts (at -60 mV, 1.7 +/- 0.2 pA/pF [failing
      hearts] versus 2.5 +/- 0.2 pA/pF [control hearts]; P < .05). The peak of the
      Ca(2+)-independent transient outward current (Ito) was dramatically reduced in
      myocytes isolated from failing hearts compared with nonfailing control hearts (at
      +80 mV, 7.0 +/- 0.9 pA/pF [failing hearts, n = 20] versus 20.4 +/- 3.2 pA/pF
      [control hearts, n = 15]; P < .001), while the steady state component was
      unchanged. There were no significant differences in Ito kinetics or single
      channel conductance. A reduction in the number of functional Ito channels was
      demonstrated by nonstationary fluctuation analysis (0.4 +/- 0.03 channels per
      square micrometer [failing hearts, n = 5] versus 1.2 +/- 0.1 channels per square
      micrometer [control hearts, n = 3]; P < .001). Pharmacological reduction of Ito
      by 4-aminopyridine in control myocytes decreased the notch amplitude and
      prolonged the APD. Current clamp-release experiments in which current was
      injected for 8 milliseconds to reproduce the notch sufficed to shorten the APD
      significantly in cells from failing hearts. These data support the hypothesis
      that downregulation of Ito in pacing-induced heart failure is at least partially
      responsible for the action potential prolongation. Because the repolarization
      abnormalities mimic those in cells isolated from failing human ventricular
      myocardium, canine pacing-induced cardiomyopathy may provide insights into the
      development of repolarization abnormalities and the mechanisms of sudden death in
      patients with heart failure.

PMID- 8575071
TI  - Angiotensin II decreases a resting K+ conductance in rat bulbospinal neurons of
      the C1 area.
AB  - In the rostral ventrolateral medulla (RVLM), angiotensin II (Ang II) receptors
      are concentrated in the region that contains neurons innervating sympathetic
      preganglionic neurons. We sought to determine whether these bulbospinal cells are
      sensitive to Ang II. Retrogradely labeled bulbospinal RVLM neurons (N = 125) were
      recorded in thin slices from neonatal rats. Most (33 of 46) histologically
      recovered bulbospinal neurons were C1 cells (immunoreactive for tyrosine
      hydroxylase [TH-ir] or phenylethanolamine N-methyltransferase [PNMT-ir]).
      Bulbospinal RVLM neurons were spontaneously active (2.7 +/- 0.2 spikes per
      second, n = 69) with 'resting' potential of -54 +/- 0.4 mV (n = 77) and input
      resistance of 879 +/- 53 M omega (n = 47). Ang II (0.3 to 1 mumol/L) increased
      the spontaneous firing rate of most bulbospinal neurons (+250%, 28 of 39). In
      current-clamp mode, Ang II (1 mumol/L) produced depolarization (+6.8 +/- 0.6 mV,
      n = 59 neurons) and increased input resistance (+21 +/- 2%, n = 36 neurons). In
      voltage-clamp mode, Ang II elicited an inward current (9.7 +/- 0.9 pA; holding
      potential, -40 to -55 mV; n = 25 neurons) that reversed polarity at the K+
      equilibrium potential (n = 8 neurons) and was barium sensitive (n = 4 neurons).
      Ang II-evoked conductance change was voltage independent (-40 to -140 mV, n = 8
      neurons). The effects of Ang II were blocked by losartan (9 of 9 neurons) but
      persisted in low Ca2+/high Mg2+ (7 of 7 neurons). Ang II-sensitive cells were
      inhibited by alpha 2-adrenergic receptor agonists (12 of 15 neurons). Ang II
      excited 91% (30 of 33) of TH-ir or PNMT-ir cells but 23% (3 of 13) of non-TH-ir
      neurons. In conclusion, RVLM bulbospinal cells express Ang II type-1 receptors
      whose activation leads to a reduction in resting K+ conductance.

PMID- 8575072
TI  - In vivo survival and function of transplanted rat cardiomyocytes.
AB  - Recent studies have demonstrated the feasibility of transplanting fetal mouse
      cardiomyocytes into the hearts of adult syngeneic mice. However, the function of
      the transplanted cardiomyocytes and their capacity to survive in fibrous
      connective tissue were not assessed. In the present study, we evaluated the
      viability and contractility of transplanted fetal and neonatal rat cardiomyocytes
      in the connective tissue of the adult rat hindlimb. Purified fetal or neonatal
      rat cardiomyocytes were cultured. These cells contained sarcomeres, formed
      junctions composed of desmosomes and fascia adherens, and contracted regularly
      and spontaneously. A fetal or neonatal cardiomyocyte suspension was injected into
      the subcutaneous tissue of adult rat hindlimbs. Cyclosporin A (5 mg/kg) was
      administered subcutaneously daily for the 3-month duration of the study, at which
      time the animals were killed. The transplanted cardiomyocytes formed 'tissue' in
      vivo that increased in size for the first 2 weeks and remained the same size at
      the third week. The tissue derived from the transplanted fetal cardiomyocytes
      contracted spontaneously at a rate of 73 +/- 12 bpm, and that from the neonatal
      cardiomyocytes contracted at a rate of 43 +/- 21 bpm. The electrocardiogram was
      similar to that seen in myocardium with an idioventricular rhythm.
      Histologically, the tissue appeared to be cardiac muscle with sarcomeres.
      Angiogenesis occurred in the cardiomyocyte graft. In summary, a cell suspension
      of cultured fetal and neonatal rat cardiomyocytes transplanted into the adult rat
      hindlimb formed contractile cardiac tissue in the subcutaneous connective tissue.

PMID- 8575074
TI  - Endothelin-1 and angiotensin II receptors in cells from rat hypertrophied heart.
      Receptor regulation and intracellular Ca2+ modulation.
AB  - This study investigates the cellular localization and regulation of endothelin-1
      (ET-1) and angiotensin II (Ang II) receptors and the effects of ET-1 and Ang II
      on [Ca2+]i in cardiac hypertrophy due to volume overload in the rat. Radioligand
      binding assays and [Ca2+]i measurements by fura 2 methodology were performed on
      isolated ventricular cardiomyocytes and fibroblasts from the heart of rats with a
      4-week aortocaval shunt. In the hypertrophied myocardium, ET-1 and Ang II
      concentrations were unchanged in ventricles. Ventricular ET-1 receptors had a
      cell-specific distribution: > 90% of ET receptors in cardiomyocytes are of the
      ETA subtype, whereas fibroblasts had a nearly equal proportion of the ETA and ETB
      subtypes. ET-1 receptor densities, affinities, and ET-1-induced [Ca2+]i were not
      significantly different from control in both ventricular cell types from
      hypertrophied myocardium. Ang II specific binding was very low on isolated
      ventricular cardiomyocytes, suggesting few receptors in control conditions.
      However, [Ca2+]i responses induced by Ang II at concentrations > 10(-8) mol/L
      were detectable and were significantly higher in hypertrophied cardiomyocytes.
      Ang II receptor density (exclusively AT1) on fibroblasts was significantly
      reduced (42,970 +/- 3330 versus 73,870 +/- 7940 sites per cell for control cells,
      P < .01), but AT1 receptor affinity was unchanged after volume overload. The
      maximum increase in [Ca2+]i evoked by 10(-6) to 10(-4) mol/L Ang II was
      significantly lower in fibroblasts from overloaded hearts. In conclusion, ET-1
      receptor proportion is cell specific, with cardiomyocytes possessing
      predominantly the ETA subtype and fibroblasts possessing both ETA and ETB
      receptors. Plasma and cardiac ET-1 concentrations and ET-1 receptor regulation on
      both ventricular cell types are not altered in cardiac volume overload,
      suggesting that cardiac ET-1 may not play a significant role in this model.
      Cardiac hypertrophy induced a significant downregulation of AT1 receptors on
      fibroblasts, whereas total binding and [Ca2+]i sensitivity to Ang II were
      significantly enhanced in hypertrophied cardiomyocytes. This suggests that
      cardiac Ang II may be involved in the pathophysiology of the cardiac hypertrophy
      of volume overload.

PMID- 8575073
TI  - DNA synthesis in adult feline ventricular myocytes. Comparison of hypoxic and
      normoxic states.
AB  - Adult mammalian ventricular myocytes are terminally differentiated cells, and the
      prevailing perception has been that DNA synthesis and repair are not active. We
      tested the hypothesis that there is potential for DNA synthesis and repair by
      studying the ability of whole-cell extracts from adult myocytes to incorporate
      [alpha-32P]dCTP into damaged plasmids. Left ventricular myocytes were isolated
      from adult cat hearts by collagenase dissociation. Cells were maintained in room
      air (control extract, CE) or made ischemic (IE) with N2 displacement of O2 and
      extracted for total protein. The nicked form of the plasmid was produced by
      exposure to an Fe3+/ascorbic acid free radical generating system. Both IE and CE
      degraded the supercoiled form of the plasmid and incorporated [alpha-32P]dCTP
      into the nicked (32P/DNA mass; CE = 2.2, IE = 3.0) and linear forms (32P/DNA
      mass; CE = 28.7, IE = 25.2). Exposure of plasmids to UV light did not inhibit
      incorporation of label. Inhibition studies with the cell extracts suggested a
      participation of polymerase delta in myocyte DNA repair/synthesis. Myocyte
      extract was as active as extract from rapidly growing COS cells at incorporating
      labeled nucleotides into plasmid DNA. The ability of intact myocytes to
      incorporate [alpha-32P]dCTP into endogenous DNA was measured in isolated cells
      made permeable with saponin. Studies were done in room air or N2. Permeable cells
      incorporated [alpha-32P]dCTP into nuclear DNA, but maximal specific activity of
      DNA was observed at 15 minutes with ischemia and at 60 minutes with room air
      control cells (ischemia, 1.34 +/- 0.5, 0.86 +/- 0.33, 0.60 +/- 0.04; air, 1.0,
      1.28 +/- 0.20, 1.87 +/- 0.38, at 15, 30, and 60 minutes, respectively). These
      data indicate that mammalian adult ventricular myocytes can actively repair
      and/or synthesize both exogenous and endogenous DNA. A DNA synthetic response to
      cellular damage may have important pathological and clinical implications.

PMID- 8575075
TI  - EJ-Ras inhibits phospholipase C gamma 1 but not actin polymerization induced by
      platelet-derived growth factor-BB via phosphatidylinositol 3-kinase.
AB  - Transformation of fibroblast-like cells (NIH 3T3) by a constitutively activated
      GTP-bound isoform of p21ras (EJ-Ras) produces morphogenic changes characterized
      by decreased attachment to the substratum, with retraction and rounding of the
      cell body. Transformed fibroblasts lose their "stressed" conformation and adopt a
      "relaxed" morphology. The specific molecular mechanisms responsible for these
      changes remain uncharacterized. We found that EJ-Ras transformation of NIH 3T3
      cells decreased the cellular content of polymerized actin, particularly at the
      expense of actin stress fibers, but induced the accumulation of actin filaments
      in peripheral ruffling membranes. Polymerization of actin could be induced in EJ
      Ras-transformed cells by exposure to platelet-derived growth factor (PDGF)-BB to
      an extent similar to that observed in wild-type NIH 3T3 cells. In EJ-Ras cells,
      actin polymerization was independent of phospholipase C gamma 1 (PLC gamma 1)
      activity, because inositol tris-phosphate (IP3) production observed in control
      NIH 3T3 cells in response to PDGF-BB was absent. Although PDGF-BB did stimulate
      tyrosine phosphorylation of PLC gamma 1, the phospholipase was strongly inhibited
      by an inhibitory factor present in the cytoplasm of EJ-Ras-transformed cells. In
      addition, cytoplasmic extracts of EJ-Ras, but not of control cells, inhibited
      phosphatidylinositol 4,5-diphosphate (PIP2) hydrolysis catalyzed by a recombinant
      PLC gamma 1 in vitro. Although PIP2 hydrolysis could not contribute to the
      reorganization of the actin cytoskeleton induced by PDGF-BB in EJ-Ras-transformed
      cells, phosphatidylinositol 3-kinase (PI3-K) was necessary for actin
      polymerization. Wortmannin, a specific PI3-K inhibitor, not only blocked actin
      polymerization in both control and EJ-Ras-transformed cells but actually led to
      rapid actin depolymerization when these cells were exposed to PDGF-BB. Thus, in
      EJ-Ras-transformed cells, cell morphogenic changes in response to PDGF-BB rely
      importantly on PI3-K and can occur in the complete absence of IP3 production
      despite tyrosine phosphorylation of PLC gamma 1.

PMID- 8575076
TI  - Expression of endothelin-1, endothelin-3, endothelin-converting enzyme-1, and
      endothelin-A and endothelin-B receptor mRNA after angioplasty-induced neointimal
      formation in the rat.
AB  - Endothelins (ETs) are potent vasoconstrictors known to play a role in tissue
      remodeling after vascular wall injury. The molecular mechanisms for the
      expression and functions of ETs and their receptors after carotid artery
      angioplasty are not fully understood. Using quantitative reverse transcription
      and polymerase chain reaction, the present study demonstrates the temporal mRNA
      expression of ET-converting enzyme-1 (ECE-1), preproET-1, preproET-3, and both
      ETA and ETB receptors after rat carotid artery balloon angioplasty. A significant
      increase in ECE-1 mRNA was observed at 6 hours (1.8-fold increase over control, P
      < .01) and 24 hours (1.7-fold increase, P < .01) in carotid arteries after
      angioplasty. In contrast, a significant increase in preproET-1 mRNA levels was
      not observed until 3 days (1.9-fold increase, P < .05) and 7 days (2.1-fold
      increase, P < .05). A similarly delayed increase in preproET-3 mRNA was observed
      at 7 days (2.8-fold increase, P < .05) and 14 days (2.6-fold increase, P < .05)
      after angioplasty. A parallel but marked increase in ETA and ETB receptor mRNAs
      compared with preproET-1 and -3 messages was observed after angioplasty. The
      levels of ETA receptor mRNA were elevated 29.3-fold (P < .001) and 24.3-fold (P <
      .01) at 3 and 7 days, respectively, after angioplasty. The increase in ETB
      receptor mRNA occurred slightly earlier than the increase in ETA receptor mRNA,
      showing 15.1-fold increase at 1 day (P < .001) and 11.3-fold increase at 3 days
      (P < .01) after angioplasty. Immunohistochemical studies using anti-ET antibodies
      demonstrated a corresponding increase in ET immunoactivity, which was distributed
      mainly in the neointimal cells 14 days after angioplasty. The increases in ECE-1,
      ET-1, and ET-3 and their receptor expression after balloon angioplasty suggest
      that these proteins play an active role in the pathogenesis of neointimal
      formation.

PMID- 8575077
TI  - Locally produced tumor necrosis factor-alpha mediates interleukin-2-induced lung
      injury.
AB  - Interleukin (IL)-2-induced microvascular lung injury is an experimental paradigm
      commonly used to investigate the pathogenesis of the adult respiratory distress
      syndrome. Since tumor necrosis factor-alpha (TNF-alpha) is known to induce such
      an injury in vivo and since TNF-alpha is involved in other models of lung injury,
      we postulated that it might also mediate pulmonary toxicity after IL-2
      administration. The present study tested this hypothesis by evaluating the effect
      of TNF-alpha inhibition on IL-2-induced lung injury in the rat. Recombinant human
      IL-2 (10(6) U IV per rat, n = 6) elevated lung water, myeloperoxidase activity,
      and protein accumulation in bronchoalveolar lavage fluid and induced tissue
      hypoxia. Also, IL-2 enhanced lung tissue TNF-alpha mRNA and peptide (1543 +/- 496
      pg/g lung wet weight) localized to alveolar macrophages by in situ hybridization.
      In marked contrast, IL-2 failed to affect serum TNF-alpha, which remained at
      undetectable levels. Pretreatment with anti-TNF-alpha monoclonal antibody (25
      mg/kg IV, n = 7) or the TNF-alpha synthesis inhibitor rolipram (200 micrograms/kg
      IV, n = 7) attenuated lung injury and reverted tissue hypoxia. Furthermore, TNF
      alpha inhibition prevented the upregulation of lung tissue IL-1 beta, IL-6,
      cytokine-induced neutrophil chemoattractant, and E-selectin (ELAM-1) but not
      intercellular adhesion molecule-1 mRNAs in response to IL-2. These data imply
      that locally produced TNF-alpha mediates IL-2-induced lung inflammation and
      tissue injury and point to the potential utilization of TNF-alpha inhibitors in
      treating the pulmonary toxicity of IL-2 immunotherapy.

PMID- 8575078
TI  - Chronic inhalation of nitric oxide inhibits neointimal formation after balloon
      induced arterial injury.
AB  - Systemic and local intravascular NO administration inhibits neointimal formation
      after vascular injury in animal models. NO appears to attenuate smooth muscle
      proliferation both directly and indirectly by preventing the release of growth
      factors. Inhalation of low concentrations of NO dilates pulmonary vascular smooth
      muscle but does not cause systemic vasodilatation. Recently, NO inhalation was
      found to inhibit platelet function in vivo. We studied the effects of NO
      inhalation on neointimal formation after balloon-induced injury of the adult rat
      carotid artery. Beginning 60 minutes before carotid injury, rats breathed either
      air with 0 or 80 ppm NO for 14 days. Rats were killed, carotid arteries were
      fixed and paraffin-embedded, and neointimal formation was measured by analyzing
      the ratio of intimal to medial areas (I/M ratio) in carotid artery cross
      sections. Intimal hyperplasia was evident in both groups of animals, but I/M
      ratios were 43% less in animals breathing 80 ppm NO for 2 weeks than in animals
      breathing air alone (0.78 +/- 0.12 and 1.37 +/- 0.11 [mean +/- SE], respectively;
      P < .02). Similarly, 1 week after carotid injury, neointimal formation was less
      in rats breathing 80 ppm NO than in rats breathing air alone (I/M ratio, 0.39 +/-
      0.11 versus 0.76 +/- 0.06; P < .02). Breathing 20 ppm NO for 2 weeks or 80 ppm NO
      for 1 week followed by air alone for 1 week did not attenuate neointimal
      formation measured at 14 days. In anesthetized rats breathing 80 ppm NO or air
      alone for 1 hour, neither systemic blood pressure nor bleeding time differed.
      These observations demonstrate that inhaling 80 ppm NO inhibits neointimal
      formation after balloon-induced carotid artery injury in rats. NO inhalation may
      represent a safe and novel method of preventing restenosis after percutaneous
      angioplasty.

PMID- 8575079
TI  - Identification of rab12 as a secretory granule-associated small GTP-binding
      protein in atrial myocytes.
AB  - A subfamily of small GTP-binding proteins, rab, has been shown to be involved in
      regulation of vesicular traffic in eukaryotic cells. The goal of this study was
      to identify the rab proteins associated with atrial secretory granules. A
      [32P]GTP-overlay assay showed the presence of multiple small GTP-binding proteins
      on the atrial granules. By biochemical analysis, we have demonstrated that one of
      the small GTP-binding proteins associated with the atrial granules is a rab12
      protein (rab12p), one of the rab proteins that are most closely related to a Sec4
      protein of yeast. Association of rab12p with the atrial granules was confirmed by
      immunogold electron microscopy. Immunoprecipitation followed by immunoblot
      analysis with anti-rab12 antibody showed that in addition to atria, rab12p was
      expressed in multiple other organs and cell lines. These results suggest that
      rab12p may function in vesicular traffic in multiple diverse types of cells.

PMID- 8575080
TI  - The topographic distribution of the efferents from neocortical neurons is not
      only dependent upon where in the neocortex the cells develop. A transplantation
      study within one single neocortical region.
AB  - It has been proposed that the distribution of efferents developed by neocortical
      neurons depends upon where in the neocortex the cells develop, not where they
      were generated. However, the capacity of diverse isocortical areas to
      differentiate connectional characteristics belonging to other isocortical areas
      has recently been questioned in several experiments using heterotopic
      transplantation paradigms. The present study was designed to determine whether
      the principle of multipotentiality is still valid within one single isocortical
      region. Mediolateral bands of embryonic (E16) frontal neocortex were dissected
      out and grafted into the left frontal cortex of neonate hosts according to either
      correct or inverted mediolateral orientation. Five to six months after grafting,
      a retrograde tracer was injected into the dorsomedial or ventrolateral left
      neostriatum of the host. The mediolateral distribution of the cell labeling
      within the transplant was then compared to that of an equivalent frontal cortical
      area (ECA) in control cases. The results indicate that strips of embryonic
      frontal neocortex transplanted according to a correct mediolateral orientation
      are able to develop a projection towards the host striatum whose mediolateral
      topographical distribution is not significantly different from that arising from
      the frontal neocortex of control animals. The percentages of transplant cells
      labeled in the medial or lateral division of the grafts were not significantly
      different from those found medially or laterally in the ECA in control cases.
      Following inversion of the mediolateral orientation of the grafts at the time of
      transplantation, the percentages of cells labeled in the medial or lateral
      division of the grafts were nearly equal whatever the site of tracer deposit
      within the host neostriatum. These results indicate that even within one single
      neocortical region the principle of areal interchangeability is not entirely
      validated and that the development of neocortical efferents is not only guided by
      extrinsic factors.

PMID- 8575081
TI  - High potassium promotes differentiation of retinal neurons but does not favor rod
      differentiation.
AB  - Neural retinal cells of newborn rats were cultured under dissociated culture
      conditions. Differentiation of several types of retinal cells was confirmed by
      immunohistochemical detection of type-specific neural phenotypes. We used Thy-1.1
      antigen as a ganglion cell marker, HPC-1 or GABA as an amacrine cell marker and
      rhodopsin as a rod cell marker. With a high concentration of potassium (38 mM),
      expression of the respective neural phenotypes were differentially affected. High
      K+ increased the number of Thy-1.1 positive cells 6 to 8 fold, and drastically
      promoted their neurite extension. The same culture conditions, however, reduced
      considerably the number of rhodopsin positive cells, possibly due to the unique
      membrane properties of photoreceptors. A high K+ concentration also promoted
      differentiation of HPC-1 positive and GABA positive cells, but to a lesser extent
      than the Thy-1.1 positive cells. Several possibilities were examined to
      understand the effect of a high K+ concentration on retinal neural cells. The
      total cell number in cultures with a high K+ concentration was approximately half
      of that in control cultures at day 3 and slightly smaller at day 11, suggesting
      that high K+ did not have a positive general effect on the proliferation or
      survival of retinal cells. Naturally occurring neuronal death (apoptosis) is a
      well-known phenomenon during retinal development. A histochemical method for
      detecting DNA fragmentation, a step preceding apoptosis, showed that high K+ had
      no preventive effect. BrdU (bromodeoxyuridine) immunohistochemistry showed that
      high K+ did not seem to enhance proliferation of neural precursor cells. These
      results indicate that a high K+ concentration promotes the expression of neuronal
      phenotypes but is not a favorable condition for rod differentiation. Since a high
      K+ concentration is considered to induce depolarization of nerve cells, the
      present results suggest an anterograde influence from surrounding neuronal cells,
      through chronic depolarization by elevated K+, is essential for the
      differentiation and maturation of retinal cells.

PMID- 8575082
TI  - Ontogeny of arginine vasopressin-like immunoreactivity in the Brazilian opossum
      brain.
AB  - The neuropeptide arginine vasopressin is involved in many centrally mediated
      functions and brain development. In this study, we have examined the ontogeny of
      arginine vasopressin-like immunoreactivity (AVP-IR) in the Brazilian opossum
      (Monodelphis domestica) brain to further understand the involvement of AVP in the
      forming central nervous system. Monodelphis is a small pouchless marsupial and
      its pups are born in an extremely immature state before neurogenesis is
      completed. In the adult brain, cell bodies containing AVP-IR were found in
      several nuclear groups and areas, and immunoreactive fibers were found to be
      widely distributed throughout the brain. The distribution of AVP-IR in the adult
      opossum brain generally resembled that reported for other species including the
      rat, however, some differences in localization of immunoreactive cells were
      observed. In the developing opossum brain, AVP-IR was first seen in the
      mesencephalon and diencephalon between embryonic days 12 and 13. Subsequently, a
      distinct group of AVP immunoreactive cells was present in the forming supraoptic
      nucleus on day 1 of postnatal life (1 PN) and at 3 PN in the paraventricular
      nucleus. Between 1 and 3 PN, a few cells transiently expressed AVP-IR in the
      forming thalamus and tegmental area. At these ages a few immunoreactive fibers
      were also detected in the forming cerebellum. These fibers were not seen at later
      ages in these areas. By 5 PN, an increased expression of AVP-IR was seen in the
      forming supraoptic and paraventricular hypothalamic nuclei, median eminence, and
      posterior pituitary. At 7 PN, immunoreactive cells and fibers were seen in
      several forebrain areas. The distribution pattern of AVP-IR became adult-like by
      60 PN. A sex difference in the amount of AVP-IR in the lateral septum was also
      observed in the opossum brain at 60 PN. This difference persisted in the adult
      brain. Due to the early presence of AVP-IR in the Monodelphis brain before
      neurogenesis and morphogenesis is completed, we suggest that AVP may be involved
      in morphogenesis of the central nervous system. In addition, AVP may have a
      significant physiological function in regard to homeostasis before the forebrain
      contributes to these control mechanisms. Further studies, including physiological
      and developmental manipulations, will define the significance of the early
      presence of AVP during the differentiation and maturation of the central nervous
      system in Monodelphis.

PMID- 8575083
TI  - Early postnatal changes of the dopaminergic mesencephalic neurons in the weaver
      mutant mouse.
AB  - In adult weaver (wv) mutant mice up to 70% of the mesostriatal dopaminergic
      neurons are lost and major alterations of the dopaminergic dendrites of the
      substantia nigra have been described. We sought to determine the time of onset of
      these alterations. Cell counts of the main dopaminergic (DA) mesencephalic cell
      groups (A8, A9, A10), as labeled with tyrosine hydroxylase immunocytochemistry
      were done in wild-type and homozygous wv/wv pups. No loss of the DA neurons, was
      detectable at postnatal day 7 (P7), while reductions in substantia nigra (and
      retrorubral area) amounted to 35% at P14 and 47% by P21. On the other hand, the
      severe reduction of dopaminergic dendrites, particularly of their distal
      compartments was already visible from P3 on. During the first postnatal week,
      this was associated to abnormal clustering of the dopaminergic neurons. These
      early neuritic alterations were present, though to a milder degree, in
      heterozygous (wv/+) mice.

PMID- 8575084
TI  - Postnatal development of the calcium-dependency of glutamate release from rat
      cortical synaptosomes: comparison with 5-hydroxytryptamine release.
AB  - The ontogeny of the Ca(2+)-dependency of the depolarisation-induced release of
      preloaded [3H]glutamate and [3H]5-hydroxytryptamine [5-HT] from rat cortical
      synaptosomes was examined. 5-HT release was found to be exclusively Ca(2+)
      dependent at all ages studied. In contrast, glutamate release only showed a
      significant Ca(2+)-dependent component from postnatal day 10 [PND 10] onwards.
      This correlated with the ontogeny of the glutamate accumulating activity of
      synaptic vesicles, a finding consistent with vesicles being the site of Ca(2+)
      dependent release. The effectiveness of K(+)-depolarisation in inducing the
      Ca(2+)-dependent release of both transmitters increased during the early neonatal
      period, reaching near adult levels at PND20 for 5-HT and PND30 for glutamate.

PMID- 8575085
TI  - Neonatal caffeine exposure alters seizure susceptibility in rats in an age
      related manner.
AB  - Early developmental exposure to caffeine in rats results in decreased
      susceptibility to certain chemically-induced seizures in the adult. To determine
      whether this effect first appears in adulthood or is present during preceding
      developmental stages, we exposed neonatal rats to caffeine and determined seizure
      thresholds in animals 28, 42 and 70-90 days of age. Rats were unhandled or
      received either vehicle (water) or caffeine (15-20 mg/kg/day) by gavage (0.05
      ml/10 g) over postnatal days 2-6. At 28, 42, or 70-90 days of age, rats were
      infused intravenously with picrotoxin (PIC), bicuculline (BIC), pentylenetetrazol
      (PTZ), caffeine (CAFF), strychnine (STR), or kainic acid (KA). Seizure thresholds
      for each compound were analyzed as a function of neonatal treatment, sex, and
      age. At 28 days, neonatally caffeine-exposed rats had a higher seizure threshold
      only for PTZ (P < 0.03). At 42 days, neonatally caffeine-exposed rats had higher
      seizure thresholds for PIC (P < 0.0007) and PTZ (P < 0.0001) than did controls.
      These results at 28 and 42 days are compared with previously reported data that
      demonstrated that in adulthood, rats neonatally exposed to caffeine have higher
      thresholds for seizure induction with CAFF, PTZ, and KA. Thus, early
      developmental exposure to caffeine results in decreases in seizure susceptibility
      that are agent specific and may result in a delay in the decrease in seizure
      threshold that occurs for many agents between late juvenile ages and adulthood.

PMID- 8575086
TI  - The regulation of acetylated microtubules during outgrowth from cultured neurons
      of the snail, Helisoma.
AB  - Axonal stumps of cultured Helisoma trivolvis neurons express abundant acetylated
      microtubules, as a subset of total microtubules. Label completely disappears from
      the axonal remnants within approximately 1 day, and reappears in newly extended
      neurites over the course of the next 3-4 days, first in the proximal neurite as
      short, isolated segments. Acetylated microtubules occur in the neuritic shaft,
      but never in growth cones or membranous veils. Thus, acetylated microtubules are
      very labile to the signals generated by axotomy, and their proximodistal re
      expression occurs at well separated sites within the neurite as it matures.

PMID- 8575087
TI  - Developmental changes of NADPH-diaphorase neurons in the forebrain of neonatal
      and adult cat.
AB  - We examined morphological changes of neurons stained for NADPH-diaphorase (a
      marker for nitric oxide synthase, NOS) in maturing cat brains. In the newborn and
      2-week-old kittens reactive neurons were dispersed throughout the cortical
      layers, in the white matter and in subcortical structures, with dense staining in
      some thalamic nuclei. In the adult, the density of reactive neurons was
      considerably decreased in the cortex and the white matter. In the thalamus, only
      some nuclei retained a faint labeling. Morphological changes also occurred at the
      cellular level. In the neonate, stained cells had prominent, thick processes with
      numerous beads and varicosities. In the adult, the processes were longer and
      thinner, with smaller varicosities. These observations provide further evidence
      that NOS may play a role during development.

PMID- 8575089
TI  - Screening of interleukins for survival-promoting effects on cultured
      mesencephalic dopaminergic neurons from embryonic rat brain.
AB  - In order to evaluate the neurotrophic potential that interleukins may have for
      nigrostriatal dopaminergic neurons, we have applied the interleukins 1 alpha, 1
      beta, and 2 through 12 to cultures of E14 rat midbrain floor cells enriched for
      dopaminergic neurons. IL-6 and -7 were the only interleukins that modestly (130%,
      as compared to controls, 100%) promoted survival of dopaminergic neurons
      visualized by their immunoreactivity for tyrosine hydroxylase over an 8-day
      culture period. The effect was not mediated by astroglial cells. We conclude that
      most interleukins per se may not act as neurotrophic factors for dopaminergic
      neurons, although several of them occur in the embryonic and adult CNS.

PMID- 8575088
TI  - Topographical regulation of cone and rod opsin genes: parallel, position
      dependent levels of transcription.
AB  - RNase protection assays were used to follow rhodopsin and red cone opsin mRNA
      levels during bovine fetal development as a function of retinal position.
      Following induction, an equivalent radial gradient of rod and cone opsin mRNA is
      present in the fetal retina. This gradient is maintained in the adult retina even
      though no corresponding gradient in rod or cone cell density is present. Since
      the mRNA expression gradient does not progress radially, position dependent
      levels of photoreceptor-specific transcription is suggested.

PMID- 8575090
TI  - Homologous conditioned medium enhances expression of TRH in hypothalamic neurons
      in primary culture.
AB  - Primary cultures of hypothalamic cells maintained in the presence of serum were
      either kept with homologous conditioned medium (CM) (i.e. only half of the medium
      was removed at each medium change) or without (total medium change). In cultures
      with homologous CM, TRH levels were increased. The effects of CMs from various
      intervals of the primary culture were tested. The strongest increases of TRH
      levels were obtained with CM from cultures enriched with hypothalamic glia.

PMID- 8575091
TI  - Developmental role of fatty acid-binding proteins in mouse brain.
AB  - While the functions of the cytoplasmic fatty acid-binding proteins (FABPs) are
      not well defined, one possibility in neural tissue is in establishing and
      maintaining the high levels of polyunsaturated fatty acids in membrane lipids
      characteristic of this tissue and thought essential for normal function. We
      investigated the reactivity of a protein in developing mouse brain to antiserum
      prepared against rat heart (H)-FABP. By immunoblot analysis, levels of H-FABP in
      brain were nearly undetectable until fetal day 17-19, after which levels
      increased until at least postnatal day 14. Levels of H-FABP were lower in the
      adult mouse brain, suggesting a function for the protein during differentiation
      of neural tissue. In immunohistochemical studies with postnatal day 14 mouse
      brain, the most intensely stained area was the choroid plexus. H-FABP also
      localized to regions of the somatosensory cortex and to the spinal trigeminal
      nucleus. In addition, H-FABP was present in the thalamus, entorhinal and piriform
      cortex, and throughout the pontine and medullary nuclei. Tracts related to the
      auditory system, including ventral cochlear nucleus and lateral lemniscus, also
      were H-FABP-positive. In cerebellum, the molecular layer was heavily labeled in
      cells and processes; in the granule cell layer, there was punctate staining
      suggestive of mossy fiber terminals. Small cells adjacent to Purkinje cells were
      intensely stained, while the Purkinje cells were negative. We conclude that H
      FABP in brain participates in neurite formation and synapse maturation, and may
      be related to the similar pattern of expression of GABA related markers.

PMID- 8575092
TI  - Characterization of microtubule-associated protein phosphoisoforms present in
      isolated growth cones.
AB  - The presence of microtubule-associated proteins (MAPs) in growth cones has been
      analyzed by isolation of these structures and characterization of their proteins
      by immunofluorescence studies. Two major MAPs, MAP1B and tau, were present in
      growth cones of cerebellum neurons isolated from 5-day-old rats. Both MAPs could
      be modified by proline-dependent protein kinases (PDPK) with opposite effects.
      PDPK-modified MAP1B isoforms are present at the growth cones whereas PDPK
      modified tau isoforms are absent. This result suggests a different role for each
      phosphoMAP. To look for a possible PDPK involved in the modification of MAP1B at
      the growth cone, the localization of MAP and cdc2 kinases was studied. Our
      results indicate that the distribution in neuronal cells of MAP kinase is
      compatible with a possible role of this protein in modifying MAP1B.

PMID- 8575093
TI  - Ciliary neurotrophic factor promotes the terminal differentiation of v-myc
      immortalized sympathoadrenal progenitor cells in vivo.
AB  - Survival and differentiation of a sympathoadrenal progenitor cell line (termed
      MAH), transduced with a v-myc oncogene, was studied subsequent to transplantation
      in the peripheral and central nervous system of adult rats. In the brain, MAH
      cell survival depended on the secretion of ciliary neurotrophic factor (CNTF) by
      co-grafts of genetically modified glioma cells. No trophic factor supplement was
      required for development of the MAH cells in the peripheral nerve environment.
      Transplanted progenitor cells withdrew from the cell cycle within 48 h and
      differentiated into a prominent population of large sympathetic-like neurons. The
      neurons expressed the alpha subunit of the CNTF receptor and appropriate spatial
      distributions of cytoskeletal proteins and catecholamine related enzymes. The
      results identify a role for CNTF in the development of the sympathoadrenal cell
      lineage and support the concept of immortalized progenitor cells as alternatives
      to primary cells for cell replacement strategies in the nervous system.

PMID- 8575094
TI  - Effect of kainic acid-induced status epilepticus on inositol-trisphosphate and
      seizure-induced brain damage in mature and immature animals.
AB  - We investigated the role of excitatory amino acids in the activation of the
      phosphoinositide pathway during kainic acid-induced seizures in mature and
      immature animals. Kainic acid caused more severe seizures in the immature
      animals, but no hippocampal damage or induction of phosphoinositide hydrolysis.
      In mature animals, seizures were mild but severe hippocampal damage was seen and
      was associated with a marked and sustained release of inositol-trisphosphate,
      suggesting a role of this pathway and intracellular calcium stores in seizure
      induced brain damage.

PMID- 8575095
TI  - Synaptophysin and GAP-43 proteins in efferent fibers of the inner ear during
      postnatal development.
AB  - A rearrangement of afferent and efferent fibers occurs in the postnatal
      development of the inner ear. Growth and synaptogenesis was explored during this
      critical period by immunohistochemically monitoring the expression of GAP-43 and
      synaptophysin. Both proteins were colocalized in efferent fibers beyond postnatal
      day 3 (pn3). Two distinct synaptophysin- and GAP-43-positive fibers innervated
      different parts of inner hair cells in the first and second postnatal weeks,
      respectively. GAP-43-positive efferents projecting to outer hair cells
      upregulated synaptophysin with base to apex gradient between postnatal day 5 and
      postnatal day 14. In efferents projecting to outer hair cells GAP-43 was
      downregulated about 6 days beyond synaptogenesis. In efferents projecting to
      inner hair cells, however, GAP-43 remained upregulated even beyond pn18,
      indicating continuous synapse replacement of this fiber type. Both proteins thus
      improved as excellent markers for growth and synaptogenesis of distinct postnatal
      efferent fibers.

PMID- 8575096
TI  - Differentiation of photoreceptors, glia, and neurons in the retina of the cichlid
      fish Aequidens pulcher; an immunocytochemical study.
AB  - Light-microscopic immunocytochemistry was carried out to investigate the
      developmental dynamics of several neurochemical markers in the retina of blue
      acara (Aequidens pulcher). As a rule, double-label experiments were performed in
      order to determine the absolute and relative timing of the appearance of these
      markers. The diameter of eye-ball (from 0.6 to 1.2 mm) and the body length (from
      4.6 to 9.4 mm) enlarged in parallel during the observation period of 2 to 9 days
      after spawning (day 2-9); hatching took place usually on day 2. Immunoreactive
      proliferating cell nuclear antigen (ir-PCNA) was present in all neuroblasts (the
      embryonic homogeneous cell stage; day 1.0-2.0), but was lost progressively in a
      center-to-periphery and apparent proximal-to-distal sequence as the cells and
      layers differentiated. In late larvae and juveniles, ir-PCNA was confined to a
      ring of dividing neuroblasts at the retinal margin and to a population of
      scattered rod precursors in the outer nuclear layer. Immunoreactive structures of
      representative antigens progressively appeared after ir-PCNA had decayed. Around
      hatching, at the synaptic separation stage (day 2.0-2.5), luteinizing hormone
      releasing hormone-ir centrifugal fibers, visinin-ir cones, glial fibrillary
      acidic protein-ir structures and gamma-aminobutyric acid-ir cell bodies appeared,
      which were followed by the emergence of rhodopsin-ir rods and tyrosine
      hydroxylase-ir interplexiform cells (on day 2.5-3.0) and serotonin-, neuropeptide
      Y- and substance P-ir amacrine cells (on day 3.0-4.0). The results indicate that
      photoreceptor cells, and especially rods start to differentiate at an earlier
      stage of retinogenesis than has previously been proposed. In addition, an
      extraretinal tissue in the brain identified as the prospective pineal organ was
      found to be visinin- and rhodopsin-immunoreactive on day 1.5-2.0 before these
      photoreceptor-specific antigens became positive in the retina.

PMID- 8575097
TI  - Specific patterns of cortical dysfunction in dementia and Parkinson's disease
      demonstrated by the acceleration spectrum entropy of the EEG.
AB  - Acceleration spectrum entropy (ASE) was used to quantify EEG desynchronization,
      which is related to cortical activation. We investigated the ASE in control and
      patient groups with dementia (AD) and Parkinson's disease (PD). Both patient
      groups had significantly lower ASE scores corresponding with less
      desynchronization in all cortical regions. In the AD group, the ASE was
      significantly lower in the parietal region. ASE was found to be a sensitive and
      specific measure for differentiating patient groups with AD and PD from controls
      and from each other.

PMID- 8575098
TI  - Atypical EEG findings in subacute sclerosing panencephalitis.
AB  - A total of 72 EEGs from 57 patients with SSPE were studied. The EEG studies in
      SSPE revealed periodic high amplitude complexes in all except one. Besides
      periodic complexes, we found several atypical EEG findings including frontal
      rhythmic delta activity in intervals between periodic complexes,
      electrodecremental periods following EEG complexes, diffuse sharp waves and sharp
      and-slow-wave complexes over frontal regions, and focal abnormalities, such as
      sharp wave and sharp and slow wave foci, which have been rarely reported
      previously. We also described a new finding characterized by high amplitude
      generalized rhythmic sharp wave activity following periodic complexes in one
      patient.

PMID- 8575099
TI  - Qualitative and quantitative abnormalities of breath counting during brief
      generalized 3 Hz spike and slow wave 'subclinical' discharges.
AB  - We aimed to validate the technique of breath counting during overbreathing in
      revealing ictal impairment of cognition during brief generalized 3 Hz spike and
      slow wave discharges. A retrospective study of 66 patients with video
      electroencephalographic documentation of typical absence seizures revealed 8
      patients in whom there was no clinical suspicion of absences but who had brief
      (less than 4 seconds) generalized 3 Hz spike-wave discharges. The only clinical
      manifestations of the absences were abnormalities in breath counting during
      overbreathing. These consisted of slowing of speech, delay in counting,
      repetition of numbers and counting out of sequence combined with delay.
      Abnormalities were more likely to occur during longer discharges. Detection of
      these abnormalities led to important changes in the classification of the
      patients' epilepsies and in the recommendations for treatment. The technique of
      breath counting during overbreathing is a simple practical and reliable method
      for detecting even mild cognitive impairment during 3 Hz spike-wave discharges.

PMID- 8575100
TI  - Abnormal auditory P300 topography in attention deficit disorder predicts poor
      response to pemoline.
AB  - P300 is a cognitive evoked potential that evaluates attention and information
      processing. This study uses auditory and visual P300 topography to develop a
      classification of attention deficit disorder (ADD), and to find predictors of
      treatment response to the stimulant pemoline. Forty-five ADD children ages 6 to
      15 were administered auditory and visual P300 using 31 scalp electrodes. They
      were compared with 39 normals. Patients were treated with pemoline, and good and
      poor responders compared. There were no P300 differences between normals and ADD
      patients. Good and poor responders to pemoline were clinically identical. Poor
      pemoline responders had smaller right fronto-central auditory P300 amplitudes
      than good responders. The ratio of right fronto-central to parietal auditory P300
      amplitude, had a sensitivity of 0.70 and specificity of 0.76, as a test for good
      pemoline response. A ratio greater than 0.5 predicted good response to pemoline,
      while a ratio less than 0.5 predicted poor response. Treatment with pemoline
      produced no P300 changes. We conclude that P300 topography classifies ADD into
      group 1 with normal P300 topography and good response to pemoline, and group 2
      with small right fronto-central auditory P300 amplitudes and poor response to
      pemoline.

PMID- 8575101
TI  - Effect of frontal and temporal seizure foci on P50 auditory evoked potentials.
AB  - Event-related potentials have been occasionally investigated in epilepsy. We
      recorded P50 auditory evoked potentials in 25 patients with complex partial
      seizures of frontal and temporal lobe origin. P50 was significantly reduced in
      amplitude and prolonged in latency in temporal lobe seizure patients as compared
      to controls. Patients with complex partial seizures originating in the frontal
      lobes did not differ from controls in P50 amplitude. P50 attenuation differences
      may be related to interictal behavioral or cognitive changes, but could also
      reflect medication effects. Event-related potentials may be helpful in
      differentiating frontal and temporal seizure foci.

PMID- 8575102
TI  - Somatosensory evoked potential elicited by acupoint's stimulus.
AB  - Based on the observation that repeated acupoint stimulation elicits evoked
      potentials whose latency varies as a result of the stimulus intensity we assessed
      the evoked potential elicited by stimulus of three acupoints (Hegu, Shenmen and
      Houxi), comparing the results to the potentials produced by median nerve stimulus
      and nonacupunctural point. Fourteen healthy individuals were studied, and no
      modifications related to the Hegu and Shenmen point potentials increased with the
      amount of stimuli, until it reached a plateau at around 400 stimuli. It did not
      vary for Houxi and the nonacupunctural point. We conclude that the somesthesic
      afference from acupunctural points must involve control circuits that are
      quantitatively different for each point.

PMID- 8575103
TI  - Pain mechanisms and management: an update.
AB  - 1. Recent findings have further helped to elucidate the mechanisms involved in
      the transmission and modulation of pain. It is now known that pain, inflammation
      and nervous system damage results in a number of changes in peripheral nerves,
      spinal cord and supraspinal structures. These changes themselves may be
      responsible for the development and maintenance of chronic pain syndromes. 2. In
      response to these findings, new agents and techniques have been applied in the
      clinical setting and new approaches have been developed to use existing agents
      more effectively. This review presents some of the findings from recent studies
      and the implications they have for the management of pain.

PMID- 8575104
TI  - Cardiovascular actions of insulin: are they important in long-term blood pressure
      regulation?
AB  - 1. In recent years, there has been considerable interest in the possibility that
      insulin may have important cardiovascular as well as metabolic actions. Perhaps
      the best documented cardiovascular effect of insulin is to cause peripheral
      vasodilation, especially in skeletal muscle. Hyperinsulinaemia also stimulates
      sympathetic activity and causes antinatriuresis, but these effects may be linked,
      at least in part, to the metabolic actions of insulin that elicit peripheral
      vasodilation and a tendency toward hypotension. Normal, fasting levels of insulin
      appear to have very little influence on peripheral vascular resistance,
      sympathetic activity or renal sodium excretion. 2. Decreased sensitivity of the
      peripheral tissues to the metabolic effects of insulin and compensatory
      hyperinsulinaemia have been postulated to play key roles in the pathophysiology
      of diseases such as hypertension and atherosclerosis. Although impaired insulin
      action (insulin resistance) and hyperinsulinaemia often accompany essential
      hypertension, especially when associated with obesity, there is currently little
      direct evidence for a cause and effect relationship between insulin resistance,
      hyperinsulinaemia and increased arterial pressure. Chronic increases in plasma
      insulin levels in dogs and humans have not been shown to cause hypertension,
      although hyperinsulinaemia raises blood pressure in rats. 3. Further research is
      needed to determine whether there are pathophysiological conditions or genetic
      factors that may predispose humans to a hypertensive effect of hyperinsulinaemia
      and/or insulin resistance.

PMID- 8575105
TI  - Renal sympathetic and heart rate baroreflex function in conscious and isoflurane
      anaesthetized normotensive and chronically hypertensive rabbits.
AB  - 1. Baroreflex control of heart rate (HR) has been studied in normotensive (NT)
      and hypertensive (HT) awake and anaesthetized animals and man, but baroreflex
      control of sympathetic nerve activity has not been well studied. We investigated
      baroreflex control of HR and renal sympathetic nerve activity (RSNA) over a wide
      range of arterial pressure (AP) in conscious and isoflurane (ISO) anaesthetized
      NT and HT rabbits. 2. Animals were instrumented to record AP, HR and RSNA.
      Hypertension was accomplished by renal encapsulation. AP-HR and AP-RSNA
      baroreflex function curves were obtained while awake and after 1.0, 1.5, 2.0 and
      2.5% ISO. All baroreflex curves were fit to sigmoid or exponential functions. 3.
      In conscious rabbits, HT for 3-5 weeks, AP was significantly higher (75.6 +/- 0.8
      vs 102.3 +/- 8.9 mmHg); HR significantly lower (218.0 +/- 5.5 vs 189.5 +/- 5.5
      beats/min); and RSNA not different than NT rabbits (14.9 +/- 2.2 vs 9.9 +/- 3.2%
      max RSNA). 4. ISO shifted AP-HR and AP-RSNA baroreflex curves to the left in NT
      and HT animals, and significantly attenuated baroreflex range and slope. At low
      ISO concentrations, baroreflex compensation for decreases in AP is limited to
      small increases in HR and sympathetic nerve activity. At higher ISO
      concentrations, baroreflex responses to decreases in AP are lost. RSNA responses
      to increases in AP are preserved with increasing ISO concentrations while HR
      responses are progressively attenuated. The sole effect of chronic hypertension
      was to shift the AP-HR and AP-RSNA barocurves to the right along the pressure
      axis in both conscious and ISO anaesthetized animals with no additional change in
      range or slope. 5. At this stage of hypertension development, ISO anaesthesia
      affects baroreflex function equally in normotensive and hypertensive rabbits.

PMID- 8575106
TI  - omega-Conotoxin GVIA and prazosin, but not felodipine, cause postural hypotension
      in rabbits.
AB  - 1. The aim was to compare the effect of N-type calcium channel blockade by omega
      conotoxin GVIA (omega-CTX) with alpha 1-adrenoceptor or L-type calcium channel
      blockade on postural adaptation in conscious rabbits. 2. Orthostatic responses
      were assessed by rapidly tilting the rabbits through 90 degrees for 1 min. Tilts
      were performed before, 30 and 60 min after i.v. bolus administration of vehicle
      (propylene glycol 0.17 mL/kg; n = 8), prazosin (0.5 mg/kg; n = 8), felodipine (30
      micrograms/kg; n = 8) or omega-CTX (3 & 7 micrograms/kg; n = 9). 3. Prazosin,
      felodipine or omega-CTX caused significant falls in mean arterial pressure (MAP)
      with corresponding increases in heart rate (HR). Vehicle administration had no
      effect on MAP but caused a small fall in HR. 4. Before drug or vehicle
      administration, a small rise in MAP and HR occurred in response to tilt in all
      rabbits. In the vehicle treatment group, similar responses were observed to tilt
      at 30 and 60 min. Postural hypotension was observed in the prazosin treatment
      group, but not following administration of felodipine. Tilts 30 and 60 min after
      omega-CTX (3 micrograms/kg) caused an increase in HR but no change in MAP,
      different to the small pressor response observed following vehicle
      administration. However, following administration of omega-CTX 7 micrograms/kg
      (total dose, 10 micrograms/kg), significant falls in MAP with tachycardia were
      observed in response to tilt. 5. In conclusion, orthostatic hypotension was
      observed following acute alpha 1-adrenoceptor or N-type calcium channel blockade
      in the conscious rabbit. These findings are compatible with the expectation that
      agents which are directly sympatholytic interfere with postural adaptation. In
      contrast, L-type calcium channel antagonism with felodipine did not elicit
      postural hypotension.

PMID- 8575107
TI  - Force and intracellular Ca2+ during NANC-mediated relaxation of rat anococcygeus
      muscle and the effects of cyclopiazonic acid.
AB  - 1. Simultaneous recordings of tension and [Ca2+]i during NANC-mediated relaxation
      were made in the rat anococcygeus muscle under various conditions. 2. In muscles
      precontracted with guanethidine, nitrergic stimulations at 2 Hz produced a rapid
      decrease in both the tension and [Ca2+]i. 3. The nitric oxide synthase inhibitor,
      NG-nitro-L-Arginine (NOLA, 100 mumol/L) completely abolished the decreases in the
      [Ca2+]i and force response of the NANC-mediated relaxation. 4. Noradrenergic
      mediated contractions elicited by electrical field stimulation were potentiated
      by the addition of NOLA. In the absence of NOLA, the motor responses were larger
      in magnitude at 10 Hz stimulation than at 2 Hz. After NOLA, both the force
      response and the associated rise in [Ca2+]i were substantially increased in
      comparison to the control stimulations. Proportionately the potentiation of the 2
      Hz response was of a far greater magnitude than that of the 10 Hz response. 5.
      The guanylate cyclase inhibitor methylene blue (10 mumol/L), partially inhibited
      the force and [Ca2+]i response of the NANC relaxation. 6. Following exposure of
      the muscles to the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, cyclopiazonic
      acid, (10 mumol/L) the responses to NANC stimulation were inhibited. The
      attenuated relaxation response displayed a bi-phasic timecourse and the Ca2+
      change in comparison to that of the control was markedly smaller. In some cases,
      a relaxation was observed with no detectable change in the [Ca2+]i. 7. The
      results suggest that part of the relaxation response observed with NANC-mediated
      relaxation in the rat anococcygeus is dependent on Ca2+ sequestration into the
      sarcoplasmic reticulum. However, other Ca2+ lowering mechanisms and possible Ca2+
      independent mechanisms may also contribute to the NANC relaxation response.

PMID- 8575108
TI  - Electrophysiological properties of the rat middle cerebral artery at different
      levels of passive wall tension.
AB  - 1. Simultaneous measurements of intracellular membrane potential and myogenic
      tone of proximal segments of the rat middle cerebral artery, mounted in a small
      vessel myograph, were made at two levels of passive wall tension. 2. At low
      levels of passive tension (less than 0.25 mN/mm) vessels had a resting membrane
      potential of approximately -65 mV. Addition of KCl (5-60 mmol/L), BaCl2 (0.01-3
      mmol/L) or tetraethylammonium (TEA; 0.1-3 mmol/L) resulted in a concentration
      dependent depolarization, to approximately -40 mV, generally associated with a
      contractile response. After the application of high levels of passive tension (to
      approximately 2 mN/mm maximum) the resting membrane potential of the smooth
      muscle cells was -40 to -45 mV. This more positive membrane potential was
      generally associated with an increase in myogenic tone of the vessel. Under these
      conditions, addition of 5-20 mmol/L KCl resulted in a strong hyperpolarization of
      the cell along with a concomitant decrease in myogenic tone of the artery. The
      hyperpolarization and vasorelaxation induced by KCl (5-20 mmol/L) were blocked by
      BaCl2 (0.5-1 mmol/L). 3. While the addition of ryanodine (10 mumol/L) to vessels
      under low tension had no effect, when added to a vessel under high tension, this
      agent caused a rhythmic oscillation in membrane potential. This oscillation was
      augmented by BaCl2 (1 mmol/L) and inhibited by nifedipine (10 nmol/L) and 4
      aminopyridine (1 mmol/L). 4. This study suggests that the electrophysiological
      and mechanical properties of the isolated rat middle cerebral artery depend on
      the passive resting conditions under which the vessel is studied. The
      depolarization of membrane potential observed with increased passive tension
      appears to result from the closure of an inward rectifying K+ channel. These
      results indicate that the inward rectifying K+ channel plays an important role in
      regulating vascular reactivity due to its functional dependence on the mechanical
      status of the blood vessel.

PMID- 8575109
TI  - Impact of cyclo-oxygenase blockade on juxtamedullary microvascular responses to
      angiotensin II in rat kidney.
AB  - 1. Experiments were designed to evaluate the hypothesis that cyclo-oxygenase
      products modulate the influence of angiotensin II (AII) on the renal
      juxtamedullary microvasculature of enalaprilat-treated rats. 2. The in vitro
      blood-perfused juxtamedullary nephron technique was utilized to provide access to
      afferent arterioles, efferent arterioles and descending vasa recta located in the
      outer stripe of the outer medulla. 3. Baseline afferent arteriolar diameter was
      20.8 +/- 1.9 microns in kidneys subjected to cyclo-oxygenase blockade (1 mumol/L
      piroxicam), a value significantly lower than that observed in untreated kidneys
      (26.1 +/- 1.0 microns). Baseline diameters of efferent arterioles and outer
      medullary descending vasa recta did not differ between untreated and piroxicam
      treated groups. 4. Topical application of 1 nmol/L AII reduced blood flow through
      outer medullary descending vasa recta by 22 +/- 6% in untreated kidneys and by 24
      +/- 7% in piroxicam-treated kidneys. 5. In untreated kidneys, AII (0.01-100
      nmol/L) produced concentration-dependent afferent and efferent arteriolar
      constrictor responses of similar magnitudes. Neither afferent nor efferent
      arteriolar AII responsiveness was significantly altered in piroxicam-treated
      kidneys, although afferent responses exceeded efferent responses at AII
      concentrations > or = 10 nmol/L. 6. We conclude that endogenous cyclo-oxygenase
      products exert a vasodilator influence on juxtamedullary afferent arterioles
      under baseline conditions. Although cyclo-oxygenase inhibition had little effect
      on juxtamedullary microvascular responses to AII, the response to high AII
      concentrations may be modulated by cyclo-oxygenase products in a manner which
      delicately alters the relative influence of the peptide on pre- vs postglomerular
      resistances.

PMID- 8575111
TI  - Response to orthostatic stress predicts office-daytime blood pressure difference,
      but not nocturnal blood pressure fall in mild essential hypertensives: results of
      the harvest trial.
AB  - 1. The aim of the present study was to evaluate whether postural blood pressure
      (BP) change could predict office-day-time BP disparity and the nocturnal BP fall
      in young, mild essential hypertensives. We investigated 411 males aged between 18
      and 45 years with never treated borderline to mild hypertension. BP was measured
      three times after a 5 min rest in the supine position and thereafter three times
      after 2 min of standing. The mean of six BP measurements obtained during two
      visits in the lying position was defined as office BP. 2. Twenty-four hour
      ambulatory BP monitoring was performed with either the A&D TM-2420 model 7 or the
      ICR Spacelabs 90207. BP values were averaged for day- and night-time periods. The
      nocturnal BP fall was defined as the difference between the average day- and
      night-time BP. 3. The standing-lying difference was significantly inversely
      correlated with the office-daytime difference for both systolic blood pressure
      (SBP) (r = -0.34, P < 0.001) and diastolic blood pressure (DBP) (r = -0.24, P <
      0.001). These correlations did not change when the obese subjects (body mass
      index > 30 kg/m2) were excluded from the analysis. No significant correlation
      between standing-lying difference and nocturnal BP fall was found. 4. Our results
      indicate that white coat hypertension assessed as the office-daytime BP disparity
      is partially related (in a negative fashion) to the BP reaction to standing. The
      postural BP change does not predict nocturnal BP fall in young, mild essential
      hypertensives.

PMID- 8575110
TI  - Effects of dietary fibre on dimethylhydrazine-induced changes in prostanoid
      concentrations in rat colonic mucosa.
AB  - 1. This study was designed to elucidate the effects of guar gum, a dietary fibre,
      on changes in prostanoid contents induced by 1,2-dimethylhydrazine, a
      carcinogenic agent, in rat colonic mucosa. 2. Prostanoid contents were determined
      using high performance liquid chromatography; five prostanoids, namely 6-keto
      prostaglandin F1 alpha, prostaglandin F2 alpha, prostaglandin E2, prostaglandin
      D2 and thromboxane B2, were detected. 3. Four subcutaneous injections of
      dimethylhydrazine, 60 mg/kg every 6 days, increased the mucosal concentrations of
      prostaglandin E2 and thromboxane B2 by approximately 50%. Other prostanoids did
      not change significantly throughout the experiments. 4. In rats treated with
      dimethylhydrazine and a fibre diet a significant increase in thromboxane B2
      content was not observed, although a significant increase in prostaglandin E2
      content was observed. These effects were observed in rats fed with fibre diet
      over 20 days but not observed in rats fed with fibre diet over 10 days. 5. From
      these results and the report that aspirin use at low doses is effective in the
      reduction of the risk of fatal colonic cancer, inhibiting thromboxane B2
      synthesis by fibre diet might be involved in the protective effect against the
      occurrence of colonic cancer.

PMID- 8575112
TI  - Accelerated endothelial regeneration and intimal hyperplasia following a repeated
      denudation of rabbit carotid arteries: morphological and immunohistochemical
      studies.
AB  - 1. We compared endothelial regeneration and intimal thickening after endothelial
      denudation between normal and sclerotic carotid arteries (CA). Endothelial
      denudation of the right CA of rabbits formed intimal thickening covered with
      regenerated endothelial cells (EC) in 6 weeks, which was considered as the
      sclerosis model. Both CA were then denuded. Morphological and immunohistochemical
      studies using antibodies for proliferating cell nuclear antigen (PCNA), von
      Willebrand factor and macrophages were performed. 2. Regeneration of EC were
      observed 24 h after denudation on both CA, but completed earlier in the double
      denuded right CA. The density of EC in both CA increased after regeneration and
      gradually decreased afterwards. 3. After a single denudation on the left CA, PCNA
      positive cells clearly appeared in 24 h, markedly increased in 72 h both in the
      intima and media, then greatly decreased in 4 and 6 weeks. 4. After a double
      denudation of the right CA, enhancement of the intimal hyperplasia was observed.
      PCNA-positive cells markedly increased in 1 week and remained significantly
      increased in 6 weeks both in the intima and the media. 5. We concluded from these
      results that the repeated endothelial denudation caused more sustained
      proliferation of smooth muscle cells which led to an enhancement of the intimal
      hyperplasia.

PMID- 8575113
TI  - Effects of endothelin-1 on the contractility of cardiomyocytes from the
      spontaneously hypertensive rat.
AB  - 1. Disturbances in cardiovascular responsiveness to endogenous endothelin-1 (ET
      1) may play a significant role in the pathogenesis of essential hypertension. In
      this study the inotropic responses of cardiomyocytes derived from normotensive
      Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) strains to ET-1 (10(
      11)-10(-8) mol/L) were characterized. Isotonic contraction cycles of ventricular
      cardiomyocytes isolated from age-matched (11 week) WKY and SHR rats were recorded
      using a rapid digital imaging technique and evaluated by computation of a range
      of normalized parameters. 2. The maximum effect of ET-1, eliciting a 60-70%
      increase in myocyte shortening after 3 min, was observed at 10(-9) mol/L in both
      strains, and was associated with elevations in the rate of shortening and
      lengthening, abbreviated latency, contractile cycle prolongation and delayed time
      to peak shortening. 3. No evidence for a significant strain dependent difference
      in the relative responsiveness to ET-1 was detected. This finding indicates that
      altered sensitivity to ET-1 is unlikely to be a major factor underlying the
      development of hypertension in this model. 4. The distinct nature of the
      alterations in contractile parameters produced by ET-1 compared with angiotensin
      II (AII) suggests that the prevailing cellular mechanisms of action of these
      peptides are different and that ET-1 is not a paracrine or autocrine inotropic
      intermediate for AII.

PMID- 8575114
TI  - Effects of a selective endothelin A-receptor antagonist, BQ-123, in salt-loaded
      stroke-prone spontaneously hypertensive rats.
AB  - 1. We examined the effects of a selective endothelin A (ETA)-receptor antagonist,
      BQ-123, on the development of hypertension and organ damage in stroke-prone
      spontaneously hypertensive rats (SHRSP) given 1% NaCl for 6 weeks. 2. BQ-123 at
      doses of 0.7, 2.1 and 7.1 mg/day was continuously administered for 6 weeks to 8
      week old salt-loaded SHRSP, who were given water containing 1% NaCl for the
      following 6 weeks, via a subcutaneous osmotic minipump. 3. Development of high
      blood pressure was accelerated in salt-loaded SHRSP compared with that in non
      salt-loaded SHRSP. After 6 weeks of salt-loading, incidence of cerebral
      infarction, renal sclerosis and renal fibrosis were greater in salt-loaded than
      non-salt-loaded SHRSP. 4. BQ-123 attenuated the age-related rise in blood
      pressure in a dose-dependent manner. The effect coincided with reduction in the
      incidence of cerebral infarction and prevention of renal sclerosis and fibrosis.
      Kidney function was improved as observed by an increase in glomerular filtration
      rate and decreases in urinary protein excretion, blood urea nitrogen and
      fractional sodium excretion. Furthermore, BQ-123 prevented increases in the heart
      weight/bodyweight ratio and aortic wall thickness in salt-loaded SHRSP. 5. These
      results suggest that endogenous endothelin-1 (ET-1) and ETA-receptors may be, at
      least in part, involved in the pathogenesis of hypertension and organ damage in
      salt-loaded SHRSP.

PMID- 8575115
TI  - Uraemia is necessary for erythropoietin-induced hypertension in rats.
AB  - 1. There is no experimental proof that renal insufficiency is a necessary
      condition for hypertension during erythropoietin treatment. 2. The present study
      compares the effect of 3 weeks treatment with r-hu EPO (50 i.u./kg) on systolic
      blood pressure (SBP), haematocrit and plasma cGMP in an animal model of chronic
      renal failure (remnant kidney model excision) and sham-operated rats. 3. Sub
      total nephrectomy induced a significant fall in haematocrit and a significant
      increase in plasma creatinine levels. Treatment with r-hu EPO resulted in a
      significant haematocrit increase in uraemic as well as in non-uraemic rats.
      Despite this effect, r-hu EPO treatment had no effect on SBP in sham-operated
      rats. On the contrary, this treatment caused significant SBP elevation in uraemic
      rats; in these rats, SBP increase did not correlate with haematocrit increase. 4.
      Plasma cGMP concentrations were significantly higher in uraemic compared to sham
      operated rats and were not modified by r-hu EPO treatment. 5. This study provides
      evidence that renal insufficiency in rats is a prerequisite for the development
      of hypertension during erythropoietin treatment.

PMID- 8575116
TI  - Human buccal epithelial cells as a potential biochemical predictor of essential
      hypertension: identification of key cellular processes.
AB  - 1. Human cheek cell Na+/H+ antiporter activity (measured as the rate of proton
      dependent 22Na+ uptake) was determined in seven normotensive (NT) and four
      hypertensive (HT) subjects following preincubation of cheek cells with a low
      molecular weight fraction isolated from NT saliva together with the ionophore,
      nigericin. 2. Cheek cells preincubated in this manner exhibited greater Na+/H+
      antiporter activity with the mean values being 4.2 nmol Na+.mg protein.5 min for
      the NT group and 1.7 for the HT group. 3. It is possible that stimulation of Na+
      transport is due to cellular accumulation of K+ ions during preincubation which,
      in the presence of the K+/H+ selective ionophore, nigericin, can cause cellular
      reacidification promoting further 22Na+ uptake via the Na+/H+ antiporter.

PMID- 8575117
TI  - 24 hour ambulatory blood pressure profiles in the acute phase of stroke.
AB  - 1. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was used to
      evaluate the blood pressure (BP) changes in acute stroke. 2. Stroke was
      categorized according to the probable underlying vascular mechanism into lacunar
      infarction (L), thrombotic infarction (T) and intracerebral haemorrhage (ICH). A
      total of 37 stroke patients were studied (T = 21, L = 9, ICH = 7). Control
      patients (n = 15) were acute medical admissions not severely ill or in
      significant pain. ABPM was performed on day 1 and day 7 following admission. 3.
      Day 1 mean +/- s.d. 24 h systolic BP (SBP) were L (159 +/- 15.8), ICH (151 +/-
      33.4), T (147 +/- 15.2) and controls (134 +/- 17.8). Day 7 mean 24 h SBP were L
      (138 +/- 9.8), ICH (143 +/- 26.9), T (138 +/- 19) and controls (134 +/- 14.8). In
      each stroke group BP fell to levels similar to control on day 7, while control
      mean SBP remained unchanged between days 1 and 7. The highest day 1 BP and the
      greatest subsequent fall on day 7 occurred for lacunar infarction. Diastolic BP
      showed similar changes to SBP. 4. The acute stress of hospitalization does not
      appear to explain elevated BP in acute stroke. Lacunar infarction appears to be
      particularly associated with temporary BP elevation.

PMID- 8575118
TI  - Effect of dose on trough peak ratio of antihypertensive drugs in elderly
      hypertensive males.
AB  - 1. The study was undertaken in male patients aged 61-73 years with essential
      hypertension. 2. The patients had previously had their blood pressure controlled
      with the drug studied. 3. A randomized crossover study compared the effect of
      different drug doses on peak (3 h) and trough (24 h) blood pressure compared to
      placebo. 4. All drug doses used lowered blood pressure at peak response and the
      responses with different doses of angiotensin converting enzyme inhibitors were
      similar. The peak response to felodipine had some dose dependency. 5. Trough
      blood pressure was not different from placebo with enalapril, 5 and 10 mg,
      perindopril, 2 mg, felodipine, 2.5 mg but was different with enalapril, 20 and 40
      mg, perindopril, 4 and 8 mg and felodipine, 5 and 10 mg. 6. Trough peak ratio was
      dose dependent, with the greatest dependency seen with enalapril which has the
      shortest half-life. 7. When low doses of enalapril (5 or 10 mg), perindopril (2
      mg) or felodipine ER (2.5 mg) are used it is important to check blood pressure
      prior to the next dose to ensure that control is achieved and maintained.

PMID- 8575119
TI  - Progression of chronic renal disease in humans is associated with the deposition
      of basement membrane components and decorin in the interstitial extracellular
      matrix.
AB  - The degree of impairment of renal function in patients with chronic renal failure
      correlates closely with the extent of fibrosis in the tubulointerstitium, i.e. of
      interstitial extracellular matrix (ECM) accumulation. The composition of this
      pathological extracellular matrix and the relation between the ECM composition on
      the one hand and the severity of histological changes and renal function on the
      other has not been investigated. This prompted us to perform the present study.
      The severity of histological abnormalities and the composition of the
      interstitial ECM were assessed using a semiquantitative scoring technique in 57
      biopsies from patients with kidney disease of diverse etiology and variable
      degrees of renal failure and were contrasted with the results of 9 control
      biopsies. Tissue sections were stained with an indirect immunoperoxidase
      technique using antibodies against collagen I, III, IV, V, VI, laminin,
      fibronectin, decorin and heparansulphate proteoglycan core protein (HSPG).
      Collagen IV, laminin and HSPG were virtually absent from the interstitium in
      controls. These components were more widely distributed in patients and the
      extent of their deposition correlated with the severity of interstitial
      histological abnormalities. In patients with severe interstitial damage the
      deposition became diffuse. Collagen type I and III were already diffusely
      distributed in the interstitium of controls and did not increase significantly as
      interstitial damage became more severe. However, the extent of collagen III
      staining in patients was significantly higher than in controls. Decorin staining
      showed a patchy distribution both in patients and controls. The overall
      distribution was significantly increased in patients. The extent of the
      deposition of both collagen V and VI was significantly increased in patients when
      compared with controls. Only the distribution of collagen V correlated with the
      severity of histological abnormalities. Our findings suggest that an increased
      interstitial deposition of extracellular matrix substances which are generally
      regarded as basement membrane components contributes more to the development of
      interstitial fibrosis and renal failure than the deposition of the fiber forming
      interstitial collagens type I and III, which are prominent in controls and in
      patients irrespective of the severity of histological abnormalities. Decorin
      staining was significantly enhanced in patients and was found to be the best
      predictor both of the severity of interstitial fibrosis and of renal failure.
      This could mean that decorin is important in human renal pathology. Collagen V
      and VI staining was significantly increased in patients when compared with
      controls. To our knowledge this is the first study in which this is demonstrated.

PMID- 8575120
TI  - Reproducibility of the WHO classification of glomerulonephritis.
AB  - The inter-observer variation of the WHO classification of glomerulonephritis (GN)
      was studied using Kappa statistics. One hundred renal biopsies were selected with
      almost equal representation of the following types of GN: minimal change
      nephropathy, membranous GN, focal proliferative GN, diffuse mesangial
      proliferative GN, endocapillary GN, membranoproliferative GN, and crescentic GN.
      Slides stained with silver-methenamine and PAS-hematoxylin were circulated among
      the members of the panel, who made their diagnoses without knowing those of the
      other participants and without knowledge of the clinical conditions. There was a
      very good overall diagnostic agreement of 0.67 with a Kappa value of 0.61,
      figures which compete very well with other diagnostic systems analysed with Kappa
      statistics. Analysing the single types of GN, we found that the highest Kappa
      values were obtained for crescentic GN (0.81), endocapillary GN (0.79) and
      membranous GN (0.74) and the lowest Kappa values for membranoproliferative GN
      (0.40) and diffuse mesangial proliferative GN (0.44). Basically, the
      international classification of GN is founded upon light microscopy. Our results
      demonstrate that this system works generally well. The diagnostic reproducibility
      of the types with less satisfactory Kappa values can be expected to be improved
      by including immunopathology and electron microscopy.

PMID- 8575121
TI  - Renal response to prostaglandin E1 infusion in polycystic kidney disease versus
      non-polycystic renal disease.
AB  - The effect of prostaglandin E1 (PGE1) on renal function was examined in 8
      patients with autosomal dominant polycystic kidney disease (ADPKD) and 8 subjects
      with non-polycystic chronic renal disease (CRD). Intravenous PGE1 infusion (50
      micrograms/hr, for 2 hrs) resulted in a significant fall in creatinine clearance
      in ADPKD, but not in CRD. Although PGE1 had no effect on urinary sodium excretion
      and osmolar clearance in both groups, it increased significantly free water
      clearance in CRD, but not in ADPKD. Nephrogenic cyclic AMP during PGE1
      administration did not differ significantly from their respective baseline level
      in two groups. In these groups, although nephrogenic cyclic AMP correlated poorly
      with urine volume, osmolar clearance, and free water clearance, it demonstrated a
      significant negative correlation with creatinine clearance. Renal volume in ADPKD
      cases had no relation with the parameters of renal function examined during PGE1
      infusion. These data demonstrate the different responses of polycystic kidneys to
      PGE1 compared with non-polycystic kidneys.

PMID- 8575122
TI  - Ultrasonographic evaluation of the carpal tunnel syndrome in hemodialysis
      patients.
AB  - The carpal tunnel syndrome (CTS) is the most frequent clinical symptom of
      dialysis-related amyloidosis. We examined CTS by ultrasound imaging and
      correlation between CTS and bone amyloidosis was sought. One hundred and forty
      two wrists of 71 hemodialysis (HD) patients and 28 of 14 normal volunteers (group
      1) were studied. Patients on HD were divided into 4 groups based on HD duration:
      Group 2, less than 5 years; group 3, 5-10 years; group 4, 10-15 years; and group
      5, more than 15 years. The frequency of CTS increased gradually with HD duration:
      0% in group 2, 35.3% in group 3, 36.4% in group 4 and 74.1% in group 5. The
      thickness of the palmar radiocarpal ligament (PRL), corresponding to the
      posterior wall of the carpal tunnel was significantly greater in groups 4 (p <
      0.05), and 5 (p < 0.05) than in group 1 (2.25 +/- 1.30 and 3.11 +/- 1.02 in group
      4 and 5 vs 1.15 +/- 0.34 mm in group 1); and the width of the carpal tunnel (CT)
      was significantly larger in group 5 than in group 1 (6.92 +/- 1.78 in group 5 vs
      5.53 +/- 1.48 mm in group 1, p < 0.05). Wrists operated on for CTS had
      significantly increased PRL and CT compared to the control group and patients
      without CTS. Patients with CTS had wider PRL than the control and HD patients
      without CTS. Cystic radiolucent lesions (CRL) of carpal bones characteristic of
      bone amyloidosis were noted in 15 of 71 HD patients. The thickness of PRL and
      width of CT in HD patients with CRL exceeded those in patients without CRL. These
      data indicated that ultrasonographic findings of wrists were closely correlated
      with the degree of CTS and CRL. The usefulness of ultrasonographic evaluation of
      PRL thickness and CT width in the evaluation of dialysis-related amyloidosis
      should be evaluated.

PMID- 8575123
TI  - The efficacy of iron dextran for the treatment of iron deficiency in hemodialysis
      patients.
AB  - We prospectively evaluated the efficacy of intravenous iron dextran for the
      replacement of iron stores in iron deficient hemodialysis patients. Twenty-eight
      patients with serum ferritin < 100 ng/ml were treated with 100 mg intravenous
      iron dextran for ten consecutive hemodialysis treatments. Therapy was considered
      successful if the serum ferritin remained > 100 ng/ml for 4 months after
      treatment. Mean hematocrit increased from 29.1 +/- 0.9% at baseline to 33.6 +/-
      1.8% at ten weeks (p < 0.05). The mean erythropoietin dose decreased from 94.1 +/
      5.3 U/kg body weight per treatment at baseline to 82.6 +/- 4.4 U/kg body weight
      per treatment at 10 weeks (p < 0.05). The mean serum ferritin at baseline was
      38.3 +/- 5.5 ng/ml, at 2 weeks 135.9 +/- 19.7 ng/ml, at 6 weeks 114.1 +/- 22.4
      ng/ml, and 86.6 +/- 17.7 ng/ml at 10 weeks. The number of patients at the
      therapeutic target (serum ferritin > 100 ng/ml) was 13 of 28 at 2 weeks after
      therapy, 9 of 28 at 6 weeks, and 8 of 28 at 10 weeks. The initial serum ferritin
      was the variable most predictive of successful therapy. None of 15 patients with
      baseline serum ferritin less than 28 ng/ml had a serum ferritin > 100 ng/ml at 4
      months, compared with 8 of 13 (61%) with initial ferritins > or = 28 ng/ml.
      Baseline hematocrit and transferrin saturation were not predictive of therapeutic
      success. In summary, this regimen for administration of intravenous iron dextran
      resulted in improved erythropoiesis, however, at study completion iron stores
      remained inadequate in the majority of patients. Baseline serum ferritin < 28
      ng/ml was highly predictive of patients who failed to reach the therapeutic
      target.

PMID- 8575124
TI  - Re-establishment of erythropoietin responsiveness in end-stage renal failure
      following renal transplantation.
AB  - Re-establishment of erythropoietin (EPO) secretion following renal
      transplantation is poorly understood. The development of sensitive EPO
      radioimmunoassay has enabled further study of this phenomenon. Forty-one adult
      patients were studied during the first 16 weeks following renal transplantation.
      Twenty six received cyclosporin monotherapy and 15 also received prednisolone and
      azathioprine. Serum creatinine, haemoglobin (Hb), ferritin and EPO were assayed
      pre-operatively, daily for 1 week, weekly for 1 month, and fortnightly to 16
      weeks. An expected EPO value, for any Hb level, was derived by linear regression
      analysis in 144 patients with iron deficiency anemia. An observed to expected
      ratio (O/E) was calculated, a value of 1.0 implying appropriate responsiveness.
      Hb increased from 8.6 +/- 2.0 (SD) to 12.3 +/- 2.1 g/dl (p < 0.001) over 16
      weeks, an increase unaffected by ferritin status. Mean EPO concentration
      increased during the first week with a peak at day 4 (22.1 +/- 13.3 to 44.6 +/-
      40.0 mu/ml, p < 0.05), a change apparent only in patients with immediate graft
      function (24 cases). There was no correlation between EPO and Hb pre-operatively;
      however a significant inverse relationship was established by week 16 (r = 
      0.404, p < 0.02). The median O/E ratio (0.22) at baseline increased progressively
      to 1.0 at 16 weeks (p < 0.001); ratios were significantly greater in the
      immediate versus delayed function group throughout (p < 0.05). In the former
      group an O/E ratio of 1.0 was reached at 10 weeks when mean serum creatinine was
      142 +/- 48 mumol/l. Patients with poor ongoing renal function (9 cases, serum
      creatinine > 250 mumol/l at 16 weeks) had impaired Hb recovery (10.1 +/- 1.6 vs
      12.7 +/- 2.0 g/dl at 16 weeks, p < 0.05). EPO values were not different in those
      patients but median O/E ratios were significantly depressed (p < 0.05)
      throughout, the maximum O/E ratio being 0.75. Recovery of renal function is
      accompanied by a beneficial Hb response driven by EPO synthesis in the
      transplant. The O/E ratio provides a useful index to assess EPO responsiveness.
      Appropriate secretion was achieved during the first 4 months and optimized by
      immediate and satisfactory graft function.

PMID- 8575125
TI  - Dialysate CA125 in stable CAPD patients: no relation with transport parameters.
AB  - We investigated dialysate CA125 concentrations (dCA125) and its possible relation
      to transport parameters in 67 stable CAPD patients. dCA125 can be regarded as a
      reflection of mesothelial cell mass or mesothelial cell turn-over. In every
      patient a standard peritoneal permeability analysis (SPA) was done. dCA125 was
      determined in the effluent of all SPA's. The examinations were done during a 4 h
      dwell with glucose 1.36%. In 29 tests dextran 70(milligrams) was added for fluid
      kinetics. dCA125 was positively related to age (p = 0.03) and negatively to the
      duration of CAPD (p = 0.0003). No correlation existed with peritonitis incidence
      (p = 0.21). Also, no relationship was present with the mass transfer area
      coefficient of creatinine, or with net ultrafiltration. The intrinsic
      permeability to macromolecules, expressed as the restriction coefficient (rc) was
      also not related to dCA125 (p = 0.14). Data on fluid kinetics showed that neither
      transcapillary ultrafiltration rate, effective lymphatic absorption rate, the
      change in intraperitoneal volume (delta IPV) nor glucose absorption were related
      to dCA125. A subgroup of patients (n = 20) had low CA125 values (< 11 U/ml). They
      were treated with CAPD for a longer period of time (23 vs 16 months, p = 0.02),
      and had a higher rc (2.59 vs 2.23, p < 0.0001). The relationship between low
      dCA125 and duration of CAPD can possibly be explained by vanishing of the
      mesothelial layer, as has been reported in patients on long-term CAPD. The higher
      rc of the low dCA125 group is probably also related to duration of CAPD, and not
      directly to the mesothelial cell mass, as the mesothelium is no osmotic barrier
      and because no pathophysiological mechanism can explain the relationship between
      a low mesothelial cell mass and a low permeability to macromolecules. It can be
      concluded that mesothelial cell mass is negatively related to the duration of
      CAPD treatment, but mesothelial cells are unlikely to play an important role in
      transport kinetics.

PMID- 8575126
TI  - Differences in calcium kinetic pattern between CAPD and HD patients.
AB  - To assess the effect of different dialysis modalities on calcium turnover, we
      studied 57 patients on maintenance hemodialysis treatment (HD) and 38 patients on
      continuous ambulatory peritoneal dialysis (CAPD) with tracer kinetic studies
      using two calcium isotopes (45Ca by mouth and 47Ca intravenously). The two groups
      were comparable in age, sex and prevalence of diabetes. The groups did not differ
      in their serum concentrations of intact parathyroid hormone (iPTH), calcium,
      inorganic phosphate and 1,25-dihydroxyvitamin D. 25-hydroxy-vitamin D and
      alkaline phosphatase were found to be significantly higher in HD patients.
      Despite these similarities, CAPD patients showed a significantly lower calcium
      kinetic response as measured by calcium retention and plasma calcium efflux than
      HD patients. Mean calcium retention was 39.5% in HD patients compared to 31.2% in
      the CAPD group (p < 0.05). Plasma calcium efflux was significantly lower in the
      CAPD group (2.7 vs 3.2 respectively; p < 0.01). iPTH correlated with calcium
      retention and plasma calcium efflux in HD patients (r = 0.69 and r = 0.67
      respectively). In CAPD patients, the correlation coefficient between iPTH and
      calcium retention was markedly lower (r = 0.54), whereas no correlation was found
      between iPTH and plasma calcium efflux (r = 0.08). In addition, the slope of the
      correlation curve were higher in HD patients (p < 0.01 and p < 0.001,
      respectively), indicating a better response of this patient group to the action
      of parathyroid hormone. Our data are in accordance with recently published
      results showing that the dialysis modality has a major impact on bone turnover
      and on the progression of uremic bone disease. It has been shown that CAPD is an
      independent risk factor for the development of the adynamic form of renal bone
      disease. This finding may be explained by the lower response of calcium turnover
      to the action of PTH as shown here with tracer kinetic studies.

PMID- 8575127
TI  - Unusual presentations of anti-glomerular basement membrane antibody mediated
      disease are associated with delayed diagnosis and poor outcome.
AB  - Anti-glomerular basement membrane antibody mediated disease (anti-GBM disease) is
      an uncommon cause of renal failure. Presentation is usually dramatic, with renal
      failure and alveolar hemorrhage leading to an early diagnosis. In contrast, we
      here describe 3 cases which presented with atypical features, and where diagnosis
      was delayed due to the presence of other factors which were initially felt
      sufficient to explain the clinical status. No patient recovered renal function,
      and one died from sepsis. We also present data on 15 patients presenting to Guy's
      Hospital over the past 10 years with anti-GBM disease and creatinine > 500
      mumol/l. The median delay from presentation to diagnosis was 7 days, range 1-81
      days. Two patients died, and only one recovered renal function. We speculate that
      earlier referral and renal biopsy might have improved outcome in these patients,
      and recommend a policy of early biopsy in all cases of acute renal failure with
      atypical feature, delay in recovery, or where a clearcut cause is not
      established.

PMID- 8575128
TI  - A case report of mixed P- and C-ANCA positive patients with pauci-immune
      crescentic glomerulonephritis.
AB  - We describe 2 patients with pauci-immune crescentic glomerulonephritis and
      elevated titers of perinuclear and cytoplasmic anti-neutrophil cytoplasmic
      antibody (P-ANCA and C-ANCA) which were associated with both 29 and 59 kD bands
      on Western blots. The presence of C-ANCA corresponds with a clinical and/or
      histological diagnosis of Wegener's granulomatosis, but although both patients
      suffered from pulmonary complications there was no clinical nor histological
      evidence of granulomatosis. Transbronchial lung biopsy showed only interstitial
      pneumonia and old hemorrhage. Therefore, the patients' conditions were
      interpreted as microscopic polyarteritis nodosa or hitherto undefined vasculitis
      associated with ANCA.

PMID- 8575129
TI  - Reversible renal failure due to the antiphospholipid antibody syndrome, pre
      eclampsia and renal thrombotic microangiopathy.
AB  - A 27-year-old Caucasian female, with a past history of recurrent spontaneous
      abortions, was admitted with pre-eclampsia at 26 weeks' gestation during her
      sixth pregnancy. She was previously known to have antiphospholipid antibodies
      since her fifth abortion, but had no clinical or serological evidence of systemic
      lupus erythematosus. A small-for-dates infant was delivered by emergency
      Caesarean section at 27 weeks for poor placental blood flow and fetal distress.
      She was transferred to the renal unit on the sixth post partum day with pulmonary
      edema, hypertension, disseminated intravascular coagulation and acute renal
      failure. Renal biopsy showed lesions compatible with thrombotic microangiopathy
      with diffuse glomerular necrosis. She was plasma exchanged and remained dialysis
      dependent for 7 months. Antiphospholipid antibodies were present in high titres
      and were the presumed cause of her acute renal failure. The patient now has
      stable renal function with a creatinine clearance of 30 ml/min for over two
      years. The late recovery of renal function is unique in the above circumstances.

PMID- 8575131
TI  - Ketorolac-induced acute renal failure and hyperkalemia.

PMID- 8575130
TI  - Percutaneous renal biopsy: a single center experience with automated spring
      loaded "gun" type device.

PMID- 8575132
TI  - A case of membranous glomerulonephritis with elevated serum level of CA-125.

PMID- 8575133
TI  - Cytidine deaminase--a new differential tool distinguishing elderly onset
      rheumatoid arthritis from polymyalgia rheumatica?

PMID- 8575134
TI  - Prospective analysis of C1 dissociation and complement activation in patients
      with systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the results of complement analysis for assessment of
      disease activity and severity, and prediction of flares in systemic lupus
      erythematosus (SLE). METHODS: Patients with mild extra-renal flares, severe extra
      renal flares or flares of lupus glomerulonephritis were followed for eight
      months, with investigations being performed every second month. Findings in
      initial samples four months before the flares were compared with findings in a
      control group with stable disease. C-reactive protein, and circulating C1q, C4
      and C3 were determined together with two types of complexes containing C1
      inhibitor (C1 INH), C1 INH-C1r-C1s and C1 INH-C1r-C1s-C1 INH, and the C3
      breakdown product C3d. RESULTS: Enhanced formation of C1 INH-C1r-C1s appeared to
      be a marker of low specificity and was mainly seen in patients with extra-renal
      disease. Concentrations of C1 INH-C1r-C1s-C1 INH, C3d, C1q and C3 clearly varied
      according to disease activity in patients with severe disease. Interestingly,
      high C1 INH-C1r-C1s-C1 INH values were found four months before the flares in all
      but one patient with lupus glomerulonephritis. Assessment of the relative
      predictivity for a subsequent flare indicated low C1q to be the most reliable
      marker, the predictivity of the complexes being: low C1q > high C1 INH-C1r-C1s-C1
      INH > low C3 > high C3d > low C4. CONCLUSION: The importance of C1q and C1
      related events in SLE may be underestimated. In addition, our results demonstrate
      the relevance of serial complement analysis for the assessment of disease
      activity and severity.

PMID- 8575135
TI  - Phospholipids and glycosphingolipids in cultured skin fibroblasts from patients
      with progressive systemic sclerosis (scleroderma).
AB  - OBJECTIVE: A comparative investigation of glycosphingolipids and phospholipids of
      cultured skin fibroblasts from healthy donors and patients with progressive
      systemic sclerosis (SSc) was performed. METHODS: Culture techniques, qualitative
      and quantitative lipid analyses, determination of neuraminidase activity, and
      immunofluorescence microscopy were used. RESULTS: The quantitative content of
      individual phospholipids in the fibroblasts of SSc patients (PF) was equally
      elevated, on the average 2.8 times in comparison with the fibroblasts of healthy
      donors (DF). The total content of neutral glycosphingolipids was slightly
      elevated only because of a 1.5-fold increase of monoglucosylceramide in PF. A
      decrease in the amount of the gangliosides GM3 and GM1 and the absence of the
      disialogangliosides in PF in comparison with DF, were demonstrated.
      Immunofluorescent assay also showed a decrease of ganglioside epitopes on the
      cellular surface of PF in comparison with DF. The GM3-neuraminidase activity of
      PF homogenates was increased two-fold in comparison to normal values.
      CONCLUSIONS: These results are discussed in connection with abnormalities in
      membrane receptor functions, alterations in the cell phenotype and AMP-cyclase
      system activity, as well as hyperproduction of extracellular matrix proteins by
      PF.

PMID- 8575136
TI  - Comparison of cyclosporin A and methotrexate in the treatment of psoriatic
      arthritis: a one-year prospective study.
AB  - OBJECTIVE: To compare the effectiveness and toxicity of cyclosporin A (CsA) vs
      low-dose methotrexate (MTX) over a period of one year in the treatment of
      psoriatic arthritis (PsA) with peripheral involvement. METHODS: Thirty-five
      patients with PsA were enrolled in a prospective, controlled, randomized trial.
      CsA was initially given in doses of 3 mg/kg/day to a maximum permitted dose of 5
      mg/kg/day; MTX was given in oral doses of 2.5 mg every 12 hours for 3 consecutive
      doses each week up to a maximum dose of 15 mg/weekly. Clinical and laboratory
      evaluations were performed at entry and monthly thereafter. RESULTS: After 6 and
      12 months the number of painful joints, the number of swollen joints, the Ritchie
      index, the duration of morning stiffness, grip strength, CRP, the patient's and
      the physician's assessment of PsA activity, as well as the PASI, were
      significantly improved in both treatment groups. ESR values were significantly
      reduced only in the MTX group (p < 0.01), which also showed a significantly
      increase of liver enzymes. The changes in the main clinical and laboratory
      parameters during the course of CsA or MTX treatment were not significantly
      different except for the AST and ALT levels (p < 0.05). After one year of therapy
      CsA and MTX were withdrawn in 41.2% and 27.8% of the patients respectively, but
      these differences were not statistically significant. CONCLUSION: Our one-year
      prospective trial shows that low-dose CsA and MTX are both effective in the
      treatment of PsA, but the differences in the tolerability of these drugs must be
      considered at the start of therapy.

PMID- 8575137
TI  - The effects of interleukin-1 receptor antagonist on oxidant-induced arthritis in
      mice.
AB  - OBJECTIVE: The anti-arthritic reactivity of the IL-1 receptor antagonist IL-1ra
      was tested in male DBA/1xB10A(4R) mice suffering from potassium peroxochromate
      induced arthritis. METHODS: Inflammatory arthritis was induced in male
      DBA/1xB10A(4R) mice by the intraplantar application of potassium peroxochromate
      and was quantified by the determination of the arthritis index, whole blood
      chemiluminescence, serum sulfhydryls and nitric oxides. Culture supernatants of
      the fibroblasts were assayed spectrophotometrically for collagenase release.
      RESULTS: Overt arthritic symptoms, as measured by the arthritis index, were
      significantly inhibited after two intraperitoneal injections of 2 mg/kg IL-1ra.
      The phorbol-ester-stimulated chemiluminescent response of monocytes and
      polymorphonuclear leukocytes in whole murine blood, which increased 5-fold during
      the development of arthritis, was normalized to the level of healthy controls.
      The oxidation of serum sulfhydryls was inhibited by 25%, and the serum levels of
      nitric oxides was depressed by 40%. In vitro the IL-1-dependent induction of
      collagenase of rabbit synovial fibroblasts was completely suppressed in the
      presence of 0.4 mg/ml IL-1ra. CONCLUSION: IL-1ra may prove useful to control the
      consequences of enhanced free radical production in inflammatory rheumatic
      diseases.

PMID- 8575138
TI  - Gliadin immune reactivity in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether patients with rheumatoid arthritis (RA) have
      immunological or clinical evidence of gluten hypersensitivity. METHODS:
      Antigliadin antibodies (AGA) and antireticulin antibodies (ARA) were determined
      in two groups of RA patients and in a control group of patients with
      spondylarthropathies. In the first group of 42 patients with recent-onset RA, AGA
      and ARA were studied longitudinally during a one-year follow up period. In the
      second group of 36 patients with advanced RA and various abdominal symptoms
      examined by upper gastrointestinal endoscopy, AGA and ARA were determined cross
      sectionally. RESULTS: Increased AGA (IgA or IgG) levels were found in 37% (29/78)
      of all RA patients compared to 12% (3/25) of controls. ARA positivity (IgG) was
      found in 4% (3/78) of RA patients and in none of the controls. AGA positivity was
      increased in patients with early RA compared to patients with advanced disease
      (48% vs. 25%) but the difference was not statistically significant. However, no
      true gluten hypersensitivity with positive AGA and ARA together with villous
      atrophy was observed. CONCLUSION: Despite the increased AGA positivity found
      distinctively in patients with recent-onset RA, none of the RA patients showed
      clear evidence of coeliac disease. AGA positivity in early RA may indicate a role
      of the gut immune system in the initiation of RA.

PMID- 8575139
TI  - CD4+ T-lymphocytopenia without HIV infection: increased prevalence among patients
      with primary Sjogren's syndrome.
AB  - OBJECTIVE: Primary Sjogren's syndrome (1 degree SS) is an autoimmune disease,
      usually accompanied by manifest immune hyperactivity. In some cases the disease
      converts to malignant neoplasia. On the other hand, there are clinical
      similarities to HIV infection. Since the rare phenomenon of persistent depletion
      of CD4+ T-lymphocytes in peripheral blood without HIV infection was recently
      defined as idiopathic CD4+ T-lymphocytopenia (ICL), we have used the ICL criteria
      to investigate the prevalence of this phenomenon among 1 degree SS patients.
      METHODS: During the period 1988-94, 115 caucasian patients (10 males), mean age
      57.8 (range 19-82) years, with 1 degree SS were prospectively studied. Lymphocyte
      subsets were investigated by means of monoclonal antibodies and flow cytometry.
      For the detection of HIV and HTLV antibodies, we used an enzyme immunoassay (for
      HIV-1 and HIV-2), Western blot techniques (HIV-1, HIV-2, HTLV-I and HTLV-II), and
      the polymerase chain reaction procedure (HIV-1, HTLV-I and HTLV-II). HIV antigens
      were tested for with the HIV-1 p-24 Ag test. RESULTS: Six patients with 1 degree
      SS fulfilled the criteria for ICL. While the clinical condition of 5 of those six
      patients remained stable, one patient developed malignant lymphoma three years
      after her disease was classified as a case of ICL. The prevalence of ICL among
      our 115 patients with 1 degree SS was 5.2%, which is significantly higher than
      the rates reported for any other patient or population group. We have estimated
      the relative risk of ICL in 1 degree SS patients to vary from 3.4 to 6,000 (P
      values of 0.0001-0.025). CONCLUSION: We suggest that subjects with ICL should be
      carefully examined for 1 degree SS and, if its presence is confirmed, that they
      should be followed with regard to the possible complications of this disease,
      including the development of malignant lymphoma.

PMID- 8575140
TI  - Short-term effect of cold provocation on single-breath carbon monoxide diffusing
      capacity in subjects with and without Raynaud's phenomenon.
AB  - The lung diffusing capacity for carbon monoxide was determined by the single
      breath method (DLCOsb) before, during, and after immersion of the left hand in
      cold water in four groups of subjects: (i) normal individuals; (ii) subjects with
      idiopathic Raynaud's disease; (iii) patients with progressive systemic sclerosis
      without associated Raynaud's phenomenon; and (iv) patients with connective tissue
      disease associated with Raynaud's phenomenon. Our results showed significant
      differences in the evolution of DLCOsb after cold stimulation between the groups.
      Control subjects (group one) showed a transient but significant reduction in
      DLCOsb at the end of two minutes of cold stimulation, normalizing ten minutes
      later. Subjects with primary Raynaud's phenomenon (group two) showed on the
      contrary a transient but significant rise in DLCOsb after 2 minutes, while
      subjects with an isolated connective tissue disease without Raynaud's phenomenon
      (group three) showed a significant decrease in DLCOsb at both observation times.
      Patients with Raynaud's phenomenon associated with a connective tissue disease
      (group four) showed a delayed decrease in DLCOsb ten minutes after cold
      stimulation. This latter result appeared as an addition to the effects of cold
      stimulation observed in groups two and three.

PMID- 8575141
TI  - Neutrophil functions, spondylarthropathies and HLA-B27: a study of 43 patients.
AB  - OBJECTIVES: Several hypotheses have been proposed regarding the role of HLA-B27
      antigen in the pathogenesis of the spondylarthropathies. METHODS: We studied some
      neutrophil functions in vivo in patients affected by ankylosing spondylitis or by
      reactive arthritis, with or without HLA-B27, and in healthy control subjects. In
      vivo neutrophil migration was investigated by Senn's skin window technique. An
      adhesion assay was also conducted and superoxide production was measured in
      circulating and migrating neutrophils after different stimuli. RESULTS:
      Neutrophil migration in vivo was higher in the HLA-B27 positive patients than in
      the controls, while no difference was found between the HLA-B27 negative patients
      and controls. Our data showed an increased response to formyl-methionyl-leucyl
      phenylalanine by circulating neutrophils in the patients with ankylosing
      spondylitis, both HLA-B27 positive and negative, in comparison with all the other
      subjects. CONCLUSIONS: Our results revive the question of the role of HLA-B27 in
      the regulation of neutrophil migration; the reported in vivo priming of
      circulating neutrophils seems to be related to ankylosing spondylitis rather than
      to HLA-B27.

PMID- 8575142
TI  - Interleukin-10 in rheumatoid arthritis.
AB  - We studied interleukin-10 (IL-10) levels in the blood and synovial fluid (SF) of
      15 patients with RA and in the blood of 15 healthy donors (HD). RA IL-10 levels
      were significantly higher in SF than in blood (p = 0.001) and did not correlate
      with the disease activity nor with the therapy. RA patients showed significantly
      reduced blood IL-10 levels compared to the HD (p = 0.002), suggesting that IL-10
      synthesis is depressed in RA. Since IL-10 has anti-inflammatory properties,
      reducing pro-inflammatory cytokine release by monocytes and down-modulating T
      cell function, its defect in RA may play a role in perpetuating RA synovitis.

PMID- 8575143
TI  - Baker's cyst in rheumatoid arthritis: an ultrasonographic study with a high
      resolution technique.
AB  - OBJECTIVE: To determine the prevalence of popliteal cyst (Baker's cyst) in
      rheumatoid arthritis (RA), through the use of a very sensitive and non-invasive
      method, high resolution ultrasonography. The present is the first such report in
      the literature. METHODS: Ninety-nine unselected consecutive patients with RA,
      after undergoing routine clinical and laboratory evaluation, had knee radiographs
      and ultrasound examinations of both knees, the popliteal fossae and calves, using
      an Ultramark 9ATL apparatus with a 3 MHz curved array and 10 MHz linear array
      heads and color doppler ability. RESULTS: A Baker's cyst was detected in 47
      patients (47.5%) and in a total of 67 out of the 198 knees (33.8%). Four of the
      67 cysts were ruptured. Only 29 of the 67 cysts (43.3%) had been diagnosed
      clinically. A statistically significant correlation was found between the
      presence of a Baker's cyst and clinical and radiologic involvement of the knee by
      rheumatoid arthritis (p < 0.025, and p < 0.05 respectively). There was a highly
      significant correlation between the presence of a cyst and ultrasonographically
      demonstrated joint effusion (p < 0.001). CONCLUSION: Baker's cyst is very common
      in RA but it may escape clinical detection. High resolution ultrasound scanning
      of the area is a simple, highly sensitive and non-invasive technique able to
      overcome this problem. Therefore, it should be more widely employed by clinicians
      in the diagnosis of popliteal cysts, which may sometimes be accompanied by
      significant morbidity.

PMID- 8575144
TI  - HLA frequencies in HLA-B27 negative patients with reactive arthritis.
AB  - The purpose of the present work was to find out whether there is an HLA type
      common to the patients who, in spite of being B27 negative, have developed
      reactive arthritis (ReA). We compared the HLA-antigens of 25 HLA-B27 negative ReA
      patients to those of healthy control persons. No statistically significant
      differences were observed in the HLA-A, B, C, DR and DQ antigen frequencies
      between the patients and the control group. The frequency of DR4 was slightly
      lower in the patients than in the controls, although this difference was not
      statistically significant. On the other hand, 18/25 (72%) of the B27-negative ReA
      patients experienced a chronic or prolonged course of the disease. These findings
      indicate that DR4 does not contribute to the chronicity of ReA in the same way
      that it is known to do in rheumatoid arthritis (RA) or Lyme arthritis. They do
      not support the hypothesis that some other HLA-antigen, in addition to HLA-B27,
      could have a predisposing or protective effect in ReA.

PMID- 8575145
TI  - Cytidine deaminase may be a useful marker in differentiating elderly onset
      rheumatoid arthritis from polymyalgia rheumatica/giant cell arteritis.
AB  - OBJECTIVE: PMR/GCA is a relatively common inflammatory disease in the elderly
      population. Clinical differentiation from a polymyalgic onset of RA in the
      elderly can be difficult. We have examined in a preliminary study the hypothesis
      that serum cytidine deaminase (CD) may be valuable in the differential diagnosis
      of these disorders. METHODS: CD was assayed by a spectrophotometric method in 20
      patients with active PMR/GCA, both before and after treatment with prednisolone,
      and was compared with serum CD levels in 20 patients with active RA. RESULTS: CD
      levels were within the normal range (< 10 units/ml) in 36 of the 40 samples from
      patients with PMR/GCA: The mean CD in pre-treatment samples was 8.64 units/ml (SD
      7.09), and after treatment 7.20 units/ml (SD 3.53). The mean serum CD in the RA
      patients was 21.33 units/ml (SD 8.94), significantly higher than in PMR/GCA (p <
      0.0001). CONCLUSION: Serum CD levels were significantly different when proven PMR
      was compared with established, long-standing RA. Therefore, serum CD could be a
      useful diagnostic marker for differentiating PMR/GCA from active RA in older
      patients.

PMID- 8575146
TI  - Systemic lupus erythematosus relapse with lupus cystitis.
AB  - A 45-year-old woman who had been diagnosed as having systemic lupus erythematosus
      (SLE) at the age of 28 years and who had been in remission developed severe
      urinary frequency, watery diarrhea, vomiting and weight loss. She also developed
      acute renal failure and her serological examination was consistent with active
      SLE. She had a markedly decreased urinary bladder capacity of 20 ml with
      hydroureteronephrosis. Histopathological study of her urinary bladder biopsy
      specimen showed mucosal edema, infiltration by lymphocytes and granulocytes, and
      deposition of IgA in the epithelium and submucosal region. We diagnosed this as a
      case of lupus cystitis. The patient's symptoms were alleviated by bilateral
      nephrostomy and corticosteroid therapy. In the present episode the patient showed
      none of the usual symptoms of SLE. This case and others reported in the
      literature show that lupus cystitis presents with specific signs and symptoms and
      therefore, this syndrome may represent a specific clinical manifestation of SLE.

PMID- 8575147
TI  - Asymptomatic pericarditis in Adamantiadis-Behcet's disease.
AB  - Pericardial involvement in Adamantiadis-Behcet's disease (ABD) is uncommon. A 14
      year-old boy presented with fever of unknown origin, as the initial and only
      manifestation of his disease. Other features were leukopenia, abdominal
      lymphadenopathy and asymptomatic pericarditis, which is a very rare finding of
      the disease. A review of pericarditis is presented.

PMID- 8575148
TI  - Transient osteoporosis of the hip: successful response to deflazacort.
AB  - Transient osteoporosis of the hip (TOH) is an uncommon condition with a poorly
      defined aetiology. Despite its benign prognosis, its long clinical course causes
      a prolonged period of functional disability in middle-aged patients. We describe
      two patients with TOH who showed a rapid response to deflazacort, a bone-sparing
      corticoid. Deflazacort may become a useful tool to shorten the otherwise lengthy
      recovery period of TOH.

PMID- 8575149
TI  - Paleopathology, its character and contribution to understanding and
      distinguishing among rheumatologic diseases: perspectives on rheumatoid arthritis
      and spondyloarthropathy.

PMID- 8575150
TI  - Primary hypergammaglobulinemic purpura associated with IgG2 deficiency. A case
      report.
AB  - Hypergammaglobulinemic purpura is a rare disease in children. We report a case of
      a 12 year-old girl with a history of frequent infections. We found the presence
      of IgG2 deficiency despite polyclonal hypergammaglobulinemia. An IgG subclass
      determination should be obtained in every child with polyclonal
      hypergammaglobulinemia and features of immunodeficiency.

PMID- 8575151
TI  - Immune complexes from sera of patients with juvenile rheumatoid arthritis reveal
      novel 40 and 60 kd bands.
AB  - OBJECTIVE: Immune complexes (IC) have been detected in the majority of sera of
      patients with juvenile rheumatoid arthritis (JRA). Our aim was to determine the
      possible constituents of these IC. METHODS: One hundred and four sera from
      patients with JRA were separated on a Sepharose 4B column to which were bound
      F(ab')2 fragments of goat anti-human IgM antibody to separate IgM-containing IC.
      The column was sequentially eluted with 1 M ammonia and 0.1 M glycine-HCl buffer,
      pH 3. The eluted material was treated with sodium dodecyl sulfate (SDS) and
      simultaneously reduced with 2-mercaptoethanol. Individual components were then
      separated by SDS-gradient polyaclylamide gel electrophoresis and were transferred
      to nitrocellulose by Western blotting. The nitrocellulose strips were overlaid
      with the patient's own serum and developed with specific antiserum to human IgM
      and IgG. RESULTS: Four bands were noted in the majority of JRA patients,
      including a band in the 70-80 kD area to the IgM heavy chain and in the 50 kD
      area to the IgG heavy chain. Additional bands specific for JRA patients' sera
      were noted in the 40 kD and 60 kD areas. Overall, 61 of 104 sera demonstrated all
      four bands; 78 showed the 40 kD band and 73 the 60 kD band. CONCLUSION: These IC
      were previously shown to contain IgM rheumatoid factor (RF), IgG-RF, and IgG in
      addition to the 40 and/or 60 kD constituents present in the isolates. Preliminary
      studies on these constituents suggest the possibility of the 60 kD band being the
      human 60 kD mitochondrial heat shock protein. Further investigations of these
      immune complex components may aid in the understanding of the pathophysiology of
      JRA.

PMID- 8575152
TI  - Brown-Sequard syndrome as a presenting symptom of cervical myelopathy in a
      rheumatoid arthritis patient.

PMID- 8575153
TI  - Ehlers Danlos syndrome: report on an unclassifiable case.

PMID- 8575154
TI  - Prolonged elevation of antinuclear antibodies in a patient with atrial myxoma
      after tumor extirpation.

PMID- 8575155
TI  - Rheumatoid arthritis exacerbation by G-CSF treatment for bucillamine-induced
      agranulocytosis.

PMID- 8575156
TI  - Unilateral osteoarthritis and neurological deficit.

PMID- 8575157
TI  - Evaluation of two disease activity indices of systemic lupus erythematosus in
      pediatric patients.

PMID- 8575158
TI  - Computer simulations of human lung structures for medical applications.
AB  - Knowledge of the structure of the human lung has salient health effects
      applications. The clinical issues encompass: (1) aerosol therapy, the targeted
      delivery of inhaled particles to enhance the efficacies of pharmacologic drugs;
      and (2) nuclear medicine, where planar gamma camera imaging, Single Photon
      Emission Computer Tomography (SPECT) and Positron Emission Tomography (PET)
      assess the distribution patterns of radiolabeled diagnostic particles and gases.
      If the resolution of such images could be enhanced, medical regimens would
      greatly benefit. Therefore, the focused objective of our work was to develop 3-D
      mathematical descriptions of the complex airway networks within the lung. A
      Silicon Graphics workstation was used to depict the daedal structures. The
      computer-generated color illustrations presented herein are intended to
      complement medical investigation. They will assist the clinician by serving as
      templates for the lung and, thereby, providing a real basis for the analysis of
      relatively abstract images. The illustrations identify individual airways and
      could be of great importance to physicians in the treatment of airway diseases
      occurring at well defined locations (e.g. bronchogenic carcinomas). To
      demonstrate that computers can be actively integrated into medical research and
      practice we have addressed SPECT images of a subject. Computer templates will aid
      future clinical investigators in two major ways: (1) the interpretation of a
      planar gamma camera, SPECT and PET images; and (2) the design of drug testing
      protocols using inhalation exposures. Considering their usefulness for
      demonstration, the lung simulations have the potential of playing a substantive
      role in education.

PMID- 8575159
TI  - Effect of sampling frequencies and averaging resolution on medical parameters of
      auditory brainstem responses.
AB  - The amplitude ratio and latency between peaks of the auditory brainstem response
      are widely used as medical parameters of response in the clinical assessment.
      Several methodological factors affect the medical parameters. The sampling
      frequency, the resolution of the averager and filtering of the signal are
      important factors. Typically the signal is highly over-sampled in the recording
      phase. The resolution of the averager should be as good as possible to ensure
      adequacy of the amplitude parameter. The latency parameter is more tolerant to
      the reduction of the sampling frequency, and the signal can be decimated down to
      10 kHz to reduce computational complexity.

PMID- 8575160
TI  - Patterns of attractor dimensions of sleep EEG.
AB  - Low dimensional chaos is a property of many physiological oscillatory systems
      including the brain. Time series of sleep EEG records have been analyzed in the
      framework of recent developments in nonlinear dynamics. One of the
      characteristics of a chaotic time series is its attractor dimension. The running
      attractor dimension of a chaotic time series may reflect changes in states more
      accurately than manually scored records. In the present study the attractor
      dimensions of consecutive EEG segments of five sleep records were analyzed. The
      block of the EEG segment (window) was shifted by various lengths along the entire
      sleep data of each subject thus producing a running attractor dimension curve for
      each record. The attractor dimension values for different sleep stages were
      significantly different. The pattern of the running attractor dimension closely
      matched the scored hypnograms in these five sleep records.

PMID- 8575161
TI  - A system for automated procedure documentation.
AB  - Quantitative information regarding competency in performing procedures is
      invaluable in attesting to a house officer's abilities when assessments need to
      be made. Thus, the means by which procedures, proficiency, and experience can be
      recorded and organized in an automated fashion need not be any further away than
      the nearest micro-computer. The procedure documenting system (PDS) automates the
      documenting of procedures and quantitative information pertaining to these
      procedures, and shortens the time demanded of the house officer to document
      procedures from a mean of 5.5 to 1.9 min. This paper is a description of the work
      done to automate the recording of procedures performed by housestaff at a
      teaching hospital and the acceptance by housestaff. This computer program takes
      the specific information and places it into a specialized database so that house
      officers can have detailed documentation attesting to their proficiency in
      various procedures. In addition, the program director can access the database to
      document the quantity of procedures to which an individual house officer has
      attained competence.

PMID- 8575162
TI  - Exact power calculations when the dependent variable is a single proportion and
      the number of events is small.
AB  - This paper presents methods for calculating the exact power to reject the null
      hypothesis that an observed event rate is significantly lower than a clinically
      relevant alternative event rate or that the confidence interval is less than a
      specified range when the hypothesis will be tested using exact binomial
      confidence intervals. SAS programs that perform the calculations are presented
      and the results are compared with power calculations using the normal
      approximation. The method can be extended to studies involving paired comparisons
      but, in that case, it does not appear to provide a significant advantage over
      normal approximation methods.

PMID- 8575163
TI  - Pituitary response to thyrotropin, corticotropin, and gonadotropin-releasing
      hormones in lactating cows treated with sometribove for a fourth consecutive
      lactation.
AB  - The effect of chronic treatment with recombinant methionyl bovine somatotropin
      (USAN, sometribove) on anterior pituitary secretions and its target organs was
      investigated in six control and six sometribove-treated British Friesian cows.
      Cows averaged 112 and 119 d postpartum in their fourth lactation of treatment
      and, except for one control, had active corpora lutea. During each lactation,
      treated cows received sometribove injections (500 mg) every 2 wk (injection
      cycle) starting 60 +/- 3 d postpartum. On Day 9 of one injection cycle, blood was
      sampled for 390 min, starting 30 min before an intravenous injection of
      thyrotropin (TRH, 0.33 microgram/kg), corticotropin (100 microgram), and
      gonadotropin (GnRH, 200 micrograms)-releasing hormones. Baseline somatotropin
      (bST) and adrenocorticotropin (ACTH) were higher in sometribove-treated cows vs.
      controls (3.27 vs. 1.03 ng/ml and 35.24 vs. 19.28 pg/ml, respectively). Baseline
      total thyroxine, free thyroxine, triiodothyronine, prolactin, follicle
      stimulating and luteinizing hormones, estradiol, and progesterone (P4) were
      similar across treatments. Circulating cortisol levels did not differ between
      control and sometribove cows, indicating a reduced adrenal ACTH responsiveness in
      the latter. Releasing factors induced similar changes across treatments in
      hormones studied with the following exceptions: a bST spike was seen in control
      cows only, cortisol response to ACTH was reduced in treated cows, and a
      significantly higher P4 concentration was detected in the plasma of sometribove
      treated cows, suggesting increased ovarian responsiveness to GnRH-stimulated P4
      output. The study demonstrated reduced bST response to TRH, consistent with
      physiologic feedback mechanisms, whereas the release profiles of the other
      pituitary hormones were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8575164
TI  - The insulin-like growth factor-II/mannose-6-phosphate receptor is present in
      fetal bovine tissues throughout gestation.
AB  - The insulin-like growth factor-II (IGF-II) and the IGF-II/mannose-6-phosphate
      (M6P) receptor are thought to play an important role in fetal growth and
      development. We have studied the expression of the IGF-II/M6P receptor in fetal
      bovine tissues from 5 through 36 weeks' gestation. Tissues from bovine fetuses
      were extracted in buffer containing 2% Triton-X-100 and 2% sodium dodecyl sulfate
      (SDS). Aliquots of the protein extracts were analyzed by SDS polyacrylamide gel
      electrophoresis and the protein bands were transferred onto nitrocellulose.
      Immunoblotting was performed with anti-bovine IGF-II/M6P receptor antiserum. In a
      subset of experiments, ligand blotting was carried out with radiolabeled IGF-II
      and subsequent autoradiography. IGF-II/M6P receptors were expressed in all
      tissues examined, with the highest amount of receptor being present in fetal lung
      and liver. Low amounts of receptors were measured in fetal brain. The amount of
      receptor was developmentally regulated throughout fetal life. The developmental
      regulation of receptor expression varied among the different tissues. In
      conclusion, the IGF-II/M6P receptor is present in all fetal bovine tissues
      examined. The presence of the IGF-II/M6P receptor seems to be developmentally
      regulated during bovine fetal life. We hypothesize that this receptor exerts
      important biologic effects during fetal growth and tissue and organ development.

PMID- 8575165
TI  - Effect of bovine somatotropin and food deprivation on beta-adrenergic and A1
      adenosine receptor binding in adipose tissue of lactating cows.
AB  - Lactating Holstein cows were used to assess the effect of bovine somatotropin
      (bST; n = 8) and fasting (FAST; n = 4) on ligand binding to beta-adrenergic (BAR)
      and Type-1 adenosine (A1R) receptors in adipose tissue. Cows received exogenous
      bST (sometribove; 40 mg/d) or no hormone (control) for 4 d in a single-reversal
      design with a 7-d interval between treatment periods. Subcutaneous adipose tissue
      biopsies were taken on day 4 of each treatment. Eight d after the bST regimen, 4
      cows were fasted for 3 d and adipose biopsies were taken. Ligand binding was
      quantified with a postnuclear, total adipose tissue membrane preparation (100,000
      x g pellet). Binding to BAR and A1R was assessed with the antagonists
      [125I]iodocyanopindolol (ICP) and [3H]8-cyclopentyl-1,3-dipropylxanthine (DCPCX),
      respectively. The binding affinity (Kd) of BAR for ICP was not affected by bST
      but was enhanced by FAST; maximal binding (Bmax) was increased with bST treatment
      (P < 0.06) and reduced by FAST (61%, P < 0.01). Kd values for DCPCX binding to
      A1R were not changed by bST or FAST. bST did not affect Bmax for A1R; however,
      FAST reduced the Bmax by 38%. Data highlight the differential regulation of BAR
      and A1R by bST and FAST.

PMID- 8575166
TI  - Ontogeny of a specific high-affinity binding site for ovine placental lactogen in
      fetal and postnatal liver.
AB  - Ovine placental lactogen (oPL) exerts actions in sheep and rodent fetal tissues
      that growth hormone (GH) does not. However, in postnatal tissues, both oPL and GH
      possess these activities. Although a high-affinity binding site for oPL in ovine
      fetal liver has been reported, some investigators believe this to be the GH
      receptor. It was our objective to discriminate between oPL and GH binding to
      fetal liver microsomes using competitive saturation analyses. Microsomal
      membranes from fetal liver (Days 60, 90, 105, 120, and 135 of gestation) and
      postnatal liver (1 wk of age) were incubated with increasing amounts of [125I]oPL
      in the absence or presence of a 100-fold molar excess of unlabeled oPL. Saturable
      binding of [125I]oPL was observed with fetal liver and postnatal liver
      microsomes. The Kd of the oPL-binding site in fetal liver was 122.1 +/- 8.2 pM
      (mean +/- standard error), and receptor concentrations remained relatively
      constant (9.8 +/- 1.1 fmol/mg of membrane protein) across gestation. The highest
      concentration of oPL binding was detected in 1-wk postnatal liver microsomes
      (53.0 fmol/mg of membrane protein). Saturation analyses using [125I]GH and [125I]
      prolactin (PRL) were also conducted with fetal liver membrane preparations.
      Although specific binding for these two radiolabeled ligands was observed in
      control tissues, no specific binding was observed in fetal liver. These data are
      in agreement with earlier reports that a high-affinity binding site for oPL
      exists in fetal tissues. The fact that saturable binding could not be
      demonstrated for either GH or PRL with fetal liver microsomes contradicts recent
      suggestions that oPL is binding the GH receptor.

PMID- 8575167
TI  - Calcium involvement in luteinizing hormone-releasing hormone release from the
      bovine infundibulum.
AB  - Bovine infundibular (stalk median eminence) explants were incubated in vitro to
      test the hypothesis that calcium (Ca) is involved in the release of luteinizing
      hormone-releasing hormone (LHRH) from LHRH neuron terminals in cattle. Right and
      left infundibular halves from individual heifers and/or steers were randomly
      assigned to either control or treated (EGTA [a Ca chelator] or verapamil [an L
      type Ca channel antagonist]) groups. Each half was incubated in 600 microliters
      of Krebs-Ringer bicarbonate medium (KRB) in the presence or absence of a
      treatment agent for 180 min. At 30-min intervals, 500-microliters samples were
      removed from each incubated and replaced with fresh media. Spontaneous (basal)
      and depolarization-induced (60 mM potassium) LHRH release was evaluated by
      radioimmunoassay of the LHRH content in the media incubated from 91 to 120 and
      121 to 150 min of culture, respectively. The effect of treatment on
      depolarization-induced LHRH release was analyzed by comparing the differences
      between spontaneous and depolarization-induced LHRH release in control and
      treated groups. Spontaneous LHRH release was not different between control and
      1.25 mM EGTA- or 100 microM verapamil-treated halves from steers. In contrast,
      steer infundibular halves incubated with EGTA (replacing Ca in KRB and chelating
      any Ca in the media) released less LHRH during depolarization than did control
      halves. In addition, verapamil-treated (to block Ca uptake by the terminal)
      infundibular halves from steers or heifers released less LHRH in response to
      depolarization than did control halves.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8575168
TI  - Urinary excretion of glucocorticoids in the diagnosis of hyperadrenocorticism in
      cats.
AB  - In dogs and humans, the measurement of urinary corticoid excretion has become a
      standard screening test for the diagnosis of hyperadrenocorticism. Mainly because
      the urinary excretion of cortisol was considered to be very low in cats, its
      measurement was not used in the diagnosis of hyperadrenocorticism in this
      species. We therefore studied the urinary excretion of [3H]cortisol and measured
      the corticoid/creatinine (C/C) ratio in healthy cats and in cats with
      hyperadrenocorticism in order to evaluate the applicability of this measurement
      in the diagnosis of feline hyperadrenocorticism. The median urinary excretion of
      intravenously administered [3H]cortisol was 1.85% (measured as excreted 3H;
      range, 1.56 to 1.99; n = 4). High-performance liquid chromatography analysis
      showed a small peak of cortisol and a large peak consisting primarily of
      conjugates of cortisol and/or its metabolites. The 2.5 and 97.5 percentiles of
      the urinary C/C ratio in healthy cats were 2 x 10(-6) to 36 x 10(-6) (n = 42).
      The C/C ratio was significantly higher in six cats with pituitary-dependent
      hyperadrenocorticism (median, 122 x 10(-6); range 51 x 10(-6) to 272 x 10(-6)).
      The administration of a high dose of dexamethasone (0.1 mg/kg thrice daily per
      os) led to marked suppression of the C/C ratio in healthy cats (median
      suppression of the average of the C/C ratio of the first two consecutive days was
      92%; range, 74 to 96%; n = 12), as well as in five cats with pituitary-dependent
      hyperadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8575169
TI  - Microdialysis measurement of intracerebral somatostatin in the goat.
AB  - A microdialysis sampling technique for the intracerebral measurement of
      somatostatin (SS) in extracellular fluid was examined in the goat. The
      microdialysis probe (70-mm shaft, 0.5 mm outer diameter) contained at its tip a 4
      mm length of copolymer dialysis membrane (20 kDa cut-off). Artificial
      cerebrospinal fluid (artificial CSF) was pumped through the probe tip at a rate
      of 4 microliters/min with a batter-driven syringe pump, and effluent fractions of
      dialysate (120 microliters) were collected every 30 min. An in vitro recovery
      test showed that changes in the SS concentration in dialysate were highly
      correlated (r = 0.95, P < 0.01) with those in the external medium, and the
      relative recovery averaged 2.0%. As a validation for in vivo microdialysis,
      trails were conducted with conscious behaving goats wherein the inflow dialysate
      was changed transiently from artificial CSF with low potassium (2.5 mM) to a
      solution of 300 mM KCl. Potassium-induced depolarization around the probe tip
      located in the preoptic area and in the hypothalamus induced an increase in SS
      concentrations in dialysate at each location. In the most remarkable response,
      the concentrations of SS were increased 6-fold and 11-fold in the first and
      second 30-min fractions, respectively, compared with prepotassium concentrations.
      These results suggest that intracerebral SS levels in extracellular fluid could
      be estimated from conscious behaving goats by the use of our intracerebral
      microdialysis system.

PMID- 8575170
TI  - Eye banking 1995: danger and opportunity.

PMID- 8575171
TI  - Transplantation of corneal tissue from donors with diseases of the central
      nervous system.
AB  - A great deal of controversy and concern exists over potential transmission of
      central nervous system diseases by corneal transplant. The purpose of this study
      was to evaluate the available data relative to this question, pertaining
      especially to transmission of infectious dementia. From these data, determination
      of conveyance risks are possible, and rational policies for donor inclusion
      criteria can be constructed. Retrospective analysis of available published data
      regarding transmission of infectious dementias was performed. Risk of disease
      transmission was calculated from population data. Of the various forms of
      dementia, only rabies, hepatitis B, and Creutzfeldt-Jakob disease (CJD) have been
      transmitted by corneal transplantation. Transmission of the first two viruses is
      preventable by serologic testing. Prevention of CJD transmission relies on
      clinical history. Despite the possibility of transmission and the lack of
      available testing, slow virus disease (CJD) has been transmitted only once. That
      this case represents an extremely rare event is supported by a lack of successful
      transmission via corneal transplant in monkeys; lower levels of infectious agent
      in cornea than in brain; lack of successful transmission of similar human
      dementias, including Alzheimer's disease to primates; the apparent requirement
      for homozygosity at codon 129 of chromosome 20 for transmission; lack of
      transmission in 5-10% of CJD cases even after brain inoculation; and low
      numerical risk of transmission based on population data. Only 0.5-4 CJD infected
      donors per year would be expected. Current Eye Bank Association of America
      criteria for donor exclusion based on suspicious history are adequate to protect
      against accidental conveyance of transmissible dementia.

PMID- 8575172
TI  - Morphologic assessment of corneal endothelium by specular microscopy in
      evaluation of donor corneas for transplantation.
AB  - Our purpose was to evaluate the role of specular microscopy in the assessment of
      donor corneas for transplantation. We conducted retrospective analysis of
      specular microscopic evaluations of 1,000 consecutive donor corneas processed at
      Mayo Clinic Eye Bank from 1986 to 1993. Thirty-four of the 1,000 corneas were
      excluded from transplantation use on the basis of specular microscopic
      examination. Twenty-four corneas were excluded because of the presence of dark
      spots on the endothelium that did not clear with time. Large endothelial cells
      were found in six corneas on inspection, with a mean cell density of 1,160
      cell/mm2 (795-1,597 cells/mm2). The remaining four excluded corneas showed
      evidence of endothelial trauma. Of 966 corneas not excluded, 520 (mean cell
      density 2,632 cells/mm2, range 1,621-4,590 cells/mm2) were transplanted at the
      Mayo Clinic, and the rest were distributed for transplantation elsewhere, when
      possible. Six of the corneas transplanted at the Mayo Clinic (1.2%) failed
      primarily. There ware no significant differences in the preoperative
      characteristics of the donor corneas between the donor failures and the clear
      grafts. Specular microscopic examination excluded 3.4% of donor corneas on the
      basis of unsatisfactory endothelium. Despite examination of the endothelium, six
      of 520 transplanted corneas (1.2%) suffered primary graft failure. Morphologic
      assessment of donor corneal endothelium by specular microscopy probably lessens,
      but does not eliminate, the risk of primary donor failure.

PMID- 8575173
TI  - The impact on tissue utilization of screening donor corneas by specular
      microscopy at the University of Texas Southwestern Medical Center.
AB  - To determine how frequently specular microscopy results affect the outcome of eye
      bank judgments on the transplantability of donor corneas, 1,011 consecutive donor
      records from a 3-year period at the Transplant Services Center of the University
      of Texas Southwestern Medical Center at Dallas were analyzed. Specular microscopy
      cell counts from each decade of donor age were determined, and it was found that
      there were no cell counts < 2,000 mm2 for any donor age < 40. Above age 40, the
      percentage of cell counts < 2,000 per mm2 rose from 3.9% for donors in their
      forties of 6% for donors in their seventies. For donors between 40 and 69 years,
      specular microscopy was used to rule out unacceptable tissue in an additional
      3.3% of a prescreened pool of corneas evaluated by current Eye Bank Association
      of America standards. While corneas from donors over age 69 were initially
      presumed to be unacceptable for transplant at this eye bank, routine specular
      microscopic examination helped to clear for transplant of 31 corneas from donors
      of this age group.

PMID- 8575174
TI  - Benefits of specular microscopy in evaluating eye donors aged 66 and older.
AB  - In the United States of America and worldwide, supplies of quality donor corneas
      continue to lag behind the demand. Some of what appears to be a shortage in the
      U.S.A. is really due to the custom of many surgeons to use only tissue from
      younger donors, thus creating an unnecessary waiting list. In reality, we do have
      a sizable pool of good donors in the older age group. With improved evaluation
      techniques, it is possible to identify these donors and to add their tissue to
      the supply of available corneas. This study shows that large numbers of corneas
      from donors over the age of 65 can be used successfully to restore vision.
      Specular microscopy provides valuable quantitative data to the surgeon, who
      ultimately makes the decision about the suitability of the donor tissue. For an
      eye bank, specular microscopy makes it easier to place older tissue, resulting in
      shorter waiting lists.

PMID- 8575175
TI  - Tissue utilization at the Minnesota Lions' Eye Bank.
AB  - The purpose of this study was to examine the utilization of corneas procured by
      the Minnesota Lions' Eye Bank to determine why corneas were excluded from
      transplantation and to identify methods to safely increase the number of tissues
      made available for transplantation. We performed a retrospective review of the
      eye bank charts of 2,382 corneas evaluated by the Minnesota Lions' Eye Bank
      between December 1, 1992 and November 30, 1993. During that time 748 corneas
      (31%) were made available for transplantation; 1,597 (67%) were directed toward
      research or training. Thirty-seven corneas (1.5%) were disposed of for safety
      reasons. Six hundred and sixty of the corneas which were excluded from
      transplantation (40%) were excluded for a donor aged over 75 years. Three hundred
      and ninety-one corneas (24%) were rejected because of a contraindication in the
      donor's past ocular or medical history. Another 395 corneas (24%) were excluded
      for poor tissue quality. The most common reason for exclusion of tissue based on
      tissue quality was abnormalities seen on specular microscopic examination (200
      corneas). Of interest, only 14 corneas were rejected for low endothelial cell
      counts. This review of our tissue evaluation process has led us to reevaluate and
      change our policy regarding exclusion of corneas for epithelial defects and arcus
      senilis. These data suggest that further evaluation of the abnormalities seen on
      specular microscopic examination and their validity as exclusion criteria should
      be undertaken. Other areas for further evaluation are how to improve the
      timeliness of tissue procurement and whether excluding all tissues over age 75
      years and all postsurgical eyes is valid.

PMID- 8575176
TI  - An eye banking program for selecting donor corneas for surgical distribution.
AB  - Since fewer donated corneas have become available for surgery, we sought to chart
      the reasons to exclude them for surgical use over time. Those excluded from
      surgical use (1991-1994) were plotted using an algorithm based on the reasons for
      exclusion. Four general categories (universal contraindications [UC],
      national/local medical criteria [NLMC], serology, and morphology) yielded 13
      possible areas. UC and NLMC exclusions for 1993-1994 were higher compared with
      1991 and 1992 (p < 0.001). The proportion of corneas excluded for serological
      reasons decreased (p < 0.001) from 1991 to 1994. Exclusions due to morphology
      remained the same for all 4 years (p = NS). NLMC eliminate older donors but also
      exclude younger donors before the tissue reaches the eye bank (p > 0.001). Three
      of four of the youngest tissues ( < 30 years) are used for surgery, whereas one
      of five of the oldest ( > 70 years) is used. A quality control algorithm provides
      a heuristic and logical paradigm for noting changes from year to year. Heightened
      regulation has counteracted many gains in corneal donation fostered by favorable
      laws.

PMID- 8575177
TI  - Changing indications for penetrating keratoplasty, 1989-1993.
AB  - The purpose of this study was to identify new trends in the changing indications
      for penetrating keratoplasty. We retrospectively reviewed the clinical and
      pathologic diagnoses of 1,104 corneal buttons that had been submitted to the
      Estelle Doheny Eye Pathology Laboratory, Los Angeles, during the 5-year period
      1989-1993. The leading indications, in order of decreasing frequency, were
      pseudophakic corneal edema (24.8%), regrafts (21.3%), scarring with or without
      chronic inflammation (11.1%), keratoconus (7.1%), aphakic corneal edema (6.4%),
      and ulcerative conditions (5.8%). The incidence of pseudophakic corneal edema
      remained stable over the study period and was actually surpassed by regraft in
      the last year of the study. Although pseudophakic corneal edema remains the
      predominant indication for penetrating keratoplasty, our findings suggest that
      its occurrence rate has begun to level off.

PMID- 8575178
TI  - Video specular microscopic screening of donor corneas.

PMID- 8575179
TI  - Screening imperfections.

PMID- 8575180
TI  - Late microbial keratitis after corneal transplantation.
AB  - Infectious keratitis after penetrating keratoplasty can be devastating to the
      survival of the graft and its visual outcome. From November 1989 to October 1994,
      we treated 41 episodes of late microbial keratitis among 354 consecutive
      penetrating keratoplasty patients and reviewed their medical records
      retrospectively. The time interval between the corneal transplantation and the
      onset of graft infection was averaged 10.4 +/- 10.9 months (range: 1-52 months).
      The precipitating factors of keratitis included epithelial defect (49%), suture
      related problems (41%), use of contact lenses (17%), trichiasis (17%), dry eye
      (12%), and lid abnormalities (10%). Gram-positive cocci and gram-negative bacilli
      were associated with 51 and 40%, respectively, of the infectious keratitis, with
      Streptococcus being the most common species. Despite fortified antibiotic
      treatments, major complications such as graft failure and wound dehiscence could
      result. The overall result was that clarity was retained in only 43% of our
      grafts. We conclude that to prevent infectious keratitis there is a need to
      implement appropriate preventive measures as well as close monitoring of the
      graft after operation.

PMID- 8575181
TI  - OptiSol corneal storage medium and transmission of Treponema pallidum.
AB  - This study was conducted to provide experimental information on the probability
      of syphilis transmission resulting from corneal transplantation. To determine the
      effects of commonly employed corneal storage conditions on the survival and
      infectivity of Treponema pallidum, T. pallidum subsp. pallidum (Nichols) was
      inoculated into OptiSol storage medium or a T. pallidum survival medium at a
      concentration of 10(6)/ml and incubated in cornea viewing chambers for 24 h at 4
      degrees C. When inoculated intradermally into rabbits (0.1 ml per site), none of
      the 10 sites developed lesions from suspensions incubated in OptiSol in the
      presence or absence of 100 microgram/ml gentamicin; T. pallidum incubated in the
      survival medium yielded lesions at one of 10 sites, whereas freshly extracted
      organisms produced lesions at all 10 sites. In another set of experiments, the
      infectivity of corneal tissue from rabbits inoculated intratesticularly with 2 x
      10(7) T. pallidum 10 days earlier was determined. Corneas from five T. pallidum
      infected rabbits were excised, extracted, and tested for infectivity either
      immediately after removal or after 24-h storage in OptiSol. Recipient rabbits
      developed lesions at five of 50 intradermal sites when the corneas were neither
      stored in OptiSol nor rinsed before extraction. Corneas from 10 donor rabbits
      that were rinsed with phosphate-buffered saline to remove blood and aqueous humor
      before extraction did not yield lesions at any of 200 sites in the recipient
      animals. The results of this study indicate that retention of T. pallidum
      infectivity is poor under typical corneal storage conditions and that rabbit
      corneal tissue contains few, if any, infectious T. pallidum organisms under the
      experimental conditions employed.

PMID- 8575182
TI  - Traumatic wound dehiscence after penetrating keratoplasty.
AB  - Eighteen eyes with wound dehiscence after penetrating keratoplasty were studied.
      Keratoplasty was performed for corneal scarring (n = 8), dystrophies (n = 6),
      graft failure (n = 2), and corneal edema (n = 2). The mean duration between
      keratoplasty and wound dehiscence was 6.54 months. All eyes underwent wound
      repair with or without iris excision, lensectomy, and vitrectomy. Grafts remained
      clear in eight eyes. Five eyes developed phthisis bulbi. Visual acuity was better
      than 20/200 in seven eyes. There was no site (quadrant) specificity for
      dehiscence. Trivial trauma resulted in dehiscence in 10 of the 18 eyes. The major
      determinants of visual outcome were the force of trauma and status of the
      posterior segment. Dehiscence of the graft-host junction in all cases reflects
      its persistent weakness after surgery.

PMID- 8575183
TI  - Corneal neovascularization after penetrating keratoplasty.
AB  - The purpose of this study was to delineate the patient and surgical factors that
      contribute to the development of corneal neovascularization (CNV) after
      penetrating keratoplasty (PK). Thirty-six eyes of 36 patients with no antecedent
      CNV were enrolled in the study. Grafts were sutured to the host with 16 10-0
      nylon sutures with the knots buried alternately in either the host or donor
      corneal stroma. Multiple perioperative factors were recorded for each patient,
      and at each postoperative visit systematic corneal drawings were used to follow
      the development of neovascularization. The stroma adjacent to each suture of each
      graft was given a neovascularization score based on the extent of vessel growth
      toward the wound interface. Univariate and multivariate analyses were performed,
      including generalized estimating equations logistic regression where each eye is
      considered a cluster of observations. Thirty-four patients without preoperative
      CNV or inflammation were followed prospectively for 6-9 (mean, 7) months after
      PK. Fourteen eyes (41%) developed some degree of CNV. Indication for
      keratoplasty, age, gender, phakic status, and size of donor button were not risk
      factors for CNV development. The most significant risk factor identified for any
      degree of CNV was placement of the suture knot in the host stroma (p = 0.00007),
      with the overall relative risk of CNV associated with these knots over 2 (95%
      confidence interval, 1.1-4.2). Furthermore, the mean recipient size in eyes with
      postoperative CNV was larger than eyes that did not develop neovascularization (p
      = 0.015), and active blepharitis was associated with a fivefold increase in the
      risk of developing CNV to the wound edge (p = 0.008). Embedding suture knots in
      the host stroma, active blepharitis, and a large recipient bed are significantly
      associated with postkeratoplasty CNV.

PMID- 8575184
TI  - Penetrating keratoplasty in atopic keratoconjunctivitis.
AB  - Penetrating keratoplasty (PK) may be required for visual rehabilitation or
      tectonic purposes in patients with severe keratopathy due to atopic
      keratoconjunctivitis (AKC). The outcome of PK is often poor in such patients
      because of adnexal and ocular surface abnormalities. We studied nine AKC patients
      requiring PK and evaluated the visual outcome and prognostic factors in 11 eyes.
      The mean follow-up was 87.2 months (range, 30-180 months). Preoperatively all
      patients had visual acuity of hand motion to 20/200. Eighteen grafts were
      performed. Final visual acuity was 20/40 or better in 46% of the eyes. Ten eyes
      retained clear grafts and improved an average of 4.5 Snellen acuity lines.

PMID- 8575185
TI  - Long-term refraction and keratometry after penetrating keratoplasty for
      keratoconus.
AB  - We looked for continued corneal ectasia after penetrating keratoplasty (PK) for
      keratoconus by measuring long-term changes in keratometry and refraction after
      final suture removal. The records of 587 patients who had had PK for keratoconus
      and who had attended a single center over a 7-year period were examined. For 184
      eyes keratometry or refraction data were available from the first operated eye
      from the 6-month interval after final suture removal, and, in these patients,
      these readings were repeated as they continued to be seen for review. The changes
      in mean keratometry, spherical equivalent, and cylinder over the period of follow
      up were then calculated, and these data were assessed by regression analysis. We
      found no significant change with time in the amount of cylinder when measured by
      either refraction or keratometry. There was a trend (p = 0.075) toward an
      increase in the mean keratometry with time, suggesting a gradual flattening of
      the cornea, and there was a clinically small, but statistically significant (p <
      0.001), time-dependent increase in the residual myopia in the years after final
      suture removal. In conclusion, we found a wide range in the individual values for
      changes in keratometry or refraction in the years after suture removal following
      PK for keratoconus but no evidence overall to suggest continued corneal ectasia
      or a recurrence of keratoconus in these grafts.

PMID- 8575186
TI  - Iris ischaemia following penetrating keratoplasty for keratoconus (Urrets-Zavalia
      syndrome)
AB  - A fixed and dilated pupil is an uncommon postoperative complication after
      penetrating keratoplasty (PK) for keratoconus. Although the clinical features
      have been well described, the precise aetiology is uncertain. We performed
      anterior segment fluorescein angiography in the early postoperative period on
      three patients who developed fixed, dilated pupils after apparently uncomplicated
      surgery. All of the eyes had severe iris ischaemia. A possible role for a
      postoperative rise in intraocular pressure in the aetiology of this syndrome is
      discussed.

PMID- 8575187
TI  - Persistent epithelial defect following penetrating keratoplasty: an adverse
      effect of diclofenac eyedrops.
AB  - Association between the use of diclofenac sodium (DfNa) eyedrops and the
      development of a postkeratoplasty persistent epithelial defect (PED) of the
      cornea were studied. In 100 consecutive patients undergoing penetrating
      keratoplasty who had no limbal or conjunctival epithelial abnormalities, 12
      (12.0%) developed PED (persistence of epithelial defect for > 8 days after
      keratoplasty) postoperatively. The use of DfNa eyedrops correlated significantly
      with the development of PED (p = 0.0001, chi-square test). DfNa eyedrops were
      used in 19 eyes postoperatively, eight of which (42.1%) showed signs of PED. The
      type of preservation media, preservation time, indications for keratoplasty, or
      the surgical procedures performed did not correlate with the development of PED.
      These results indicate that DfNa eyedrops are toxic to the corneal epithelium
      postkeratoplasty. The eyedrops should be used with great care in patients with
      disorders of the corneal epithelium.

PMID- 8575188
TI  - Cytomegalovirus keratitis after penetrating keratoplasty.
AB  - We report the development of cytomegalovirus (CMV) keratitis in the penetrating
      keratoplasty of a 59-year-old human immunodeficiency virus-negative woman after
      uncomplicated corneal transplantation. Immunosuppression with topical
      cyclosporine A 2% in corn oil and topical prednisolone acetate 1% suspension was
      used postoperatively. The 15-month postoperative course was complicated by
      multiple episodes of endothelial rejection, medically controlled elevated
      intraocular pressure, polymicrobial bacterial (coagulase-negative staphlococcus
      and alpha-hemolytic streptococcus) keratitis, and endothelial plaque formation
      with associated hypopyon and epithelial defect. The graft failed and penetrating
      keratoplasty was repeated. Cytomegalovirus infection of superficial keratocytes
      in a region of scarring was identified in histological sections stained with
      hematoxylin and eosin and confirmed using mouse monoclonal anti-cytomegalovirus
      antibodies. Excision of the diseased corneal button with no additional treatment
      appears to have been curative. Low-grade keratitis was the only manifestation of
      the CMV infection, and it has not recurred 6 months postoperatively.

PMID- 8575189
TI  - Structures of protein complexes by multidimensional heteronuclear magnetic
      resonance spectroscopy.
AB  - With the advent of multidimensional heteronuclear-edited and -filtered NMR
      experiments, the field of three-dimensional structure determination by NMR has
      again increased in scope, making it possible to move the technology beyond the
      approximately 10 kDa limit inherent to conventional two-dimensional NMR to
      systems up to potentially 35 to 40 kDa. This article outlines the basic
      strategies for solving three-dimensional structures of larger systems, in
      particular, protein complexes and multimeric proteins using three- and four
      dimensional NMR spectroscopy, summarizes the key experiments, and illustrates the
      power of these methods using several examples of protein-DNA, protein-peptide
      complexes, and oligomeric proteins from the authors' laboratories.

PMID- 8575191
TI  - The CD4 molecule. Roles in T lymphocytes and in HIV disease. Introduction.

PMID- 8575190
TI  - Enzymatic degradation of glycosaminoglycans.
AB  - Glycosaminoglycans (GAGs) play an intricate role in the extracellular matrix
      (ECM), not only as soluble components and polyelectrolytes, but also by specific
      interactions with growth factors and other transient components of the ECM.
      Modifications of GAG chains, such as isomerization, sulfation, and acetylation,
      generate the chemical specificity of GAGs. GAGs can be depolymerized
      enzymatically either by eliminative cleavage with lyases (EC 4.2.2.-) or by
      hydrolytic cleavage with hydrolases (EC 3.2.1.-). Often, these enzymes are
      specific for residues in the polysaccharide chain with certain modifications. As
      such, the enzymes can serve as tools for studying the physiological effect of
      residue modifications and as models at the molecular level of protein-GAG
      recognition. This review examines the structure of the substrates, the properties
      of enzymatic degradation, and the enzyme substrate-interactions at a molecular
      level. The primary structure of several GAGs is organized macroscopically by
      segregation into alternating blocks of specific sulfation patterns and
      microscopically by formation of oligosaccharide sequences with specific binding
      functions. Among GAGs, considerable dermatan sulfate, heparin and heparan sulfate
      show conformational flexibility in solution. They elicit sequence-specific
      interactions with enzymes that degrade them, as well as with other proteins,
      however, the effect of conformational flexibility on protein-GAG interactions is
      not clear. Recent findings have established empirical rules of substrate
      specificity and elucidated molecular mechanisms of enzyme-substrate interactions
      for enzymes that degrade GAGs. Here we propose that local formation of
      polysaccharide secondary structure is determined by the immediate sequence
      environment within the GAG polymer, and that this secondary structure, in turn,
      governs the binding and catalytic interactions between proteins and GAGs.

PMID- 8575192
TI  - The structure of CD4.

PMID- 8575193
TI  - Endocytic and exocytic regulation of CD4 expression and function.

PMID- 8575194
TI  - The receptor for HIV: dissection of CD4 and studies on putative accessory
      factors.

PMID- 8575195
TI  - The role of CD4 in HIV envelope-mediated pathogenesis.
AB  - There is now compelling evidence that env-CD4 interactions are central to several
      complex pathogenic mechanisms in HIV-1 infection. In addition to mediating virus
      attachment to CD4+ cells, the high affinity interaction of env protein with CD4
      is also important in initiating both syncytium formation and syncytium
      independent cytopathic effects. In addition, shed gp120 can bind to CD4 on
      noninfected cells and interfere with the function of these cells while at the
      same time rendering the cells susceptible to destruction by ADCC, by CD4+ CTLs or
      by programmed cell death induced by cross-linking of CD4 with gp120 and anti
      gp120 followed by cellular activation. Although all of these mechanisms have been
      demonstrated to operate in vitro, it remains unclear how important each mechanism
      is in vivo. Nevertheless, the central role of env-CD4 interactions in all of
      these pathogenic mechanisms highlights the importance of developing effective low
      molecular weight inhibitors of this reaction.

PMID- 8575196
TI  - The structural basis of CD4-MHC class II interactions: coreceptor contributions
      to T cell receptor antigen recognition and oligomerization-dependent signal
      transduction.

PMID- 8575197
TI  - CD4 and signal transduction.
AB  - The CD4 molecule plays an important role in the development of CD4+T lymphocytes
      and it also acts as a coreceptor to enhance responses mediated via the TCR. It is
      now established that CD4 functions both as an adhesion molecule favoring the T
      cell: APC interaction and as a signaling molecule. The coreceptor function
      mediated via CD4 depends on its association with Lck, a src-family tyrosine
      kinase. Lck, while interacting via its unique NH2-terminal domain with CD4, also
      interacts via its SH2 and SH3 domains with other intracellular signaling
      proteins. Although the Lck association with CD4 is essential for CD4 coreceptor
      activity, the tyrosine kinase activity of CD4-associated Lck appears to be
      dispensable for CD4 function. Given the necessity of Lck kinase activity for T
      lymphocyte development and for mature T cell functions, perhaps Lck may function
      at different stages during T cell activation and at some stages the kinase
      activity of Lck may not be necessary. This raises an intriguing possibility that
      CD4-associated Lck may function more as an adapter protein than a kinase and may
      help to recruit other signaling proteins into the TCR/CD3 complex. However,
      determination of the precise role of Lck in CD4 coreceptor activity and the
      domains of Lck that are necessary for CD4-dependent and CD4-independent functions
      awaits further experiments.

PMID- 8575198
TI  - Signal transduction by the lymphocyte-specific tyrosine protein kinase p56lck.

PMID- 8575199
TI  - The regulation and function of the CD4 coreceptor during T lymphocyte
      development.
AB  - The data reviewed in this chapter suggest that the primary developmental function
      of the CD4 and CD8 coreceptors is to improve the efficacy by which a thymocyte
      recognizes peptide/MHC. During positive selection, DP thymocytes down-regulate
      expression of either CD4 or CD8 in response to signals that originate from the
      TCR/coreceptor complex. Experiments with transgenic and MHC-null mice have shown
      that coreceptor down-regulation and lineage commitment can occur stochastically
      in a manner that is independent of TCR specificity for MHC. Nevertheless, the
      positive selection of a given thymocyte is contingent on sustained expression of
      the coreceptor that is appropriate for the MHC specificity of its TCR. In most
      cases, loss of the required coreceptor blocks developmental progression and
      results in thymocyte apoptosis. CD4 expression is controlled by both positive and
      negative regulatory sequences embedded in the CD4 gene and it is likely that
      similar sequences regulate the CD8 gene. The down-regulation of coreceptor
      expression is coupled to a functional commitment which ensures that mature CD4+ T
      cells have a helper phenotype and CD8+ T cells have a cytotoxic phenotype. The
      molecular basis for this coupling and the identity of the switching mechanism
      which governs coreceptor regulation remain to be determined.

PMID- 8575200
TI  - Human prion diseases and neurodegeneration.

PMID- 8575201
TI  - Transgenetics and neuropathology of prion diseases.

PMID- 8575202
TI  - Evidence for two prions in yeast: [URE3] and [PSI].

PMID- 8575203
TI  - Fatal familial insomnia and familial Creutzfeldt-Jakob disease: a tale of two
      diseases with the same genetic mutation.

PMID- 8575204
TI  - Human prion disease and human prion protein disease.

PMID- 8575205
TI  - Prion strains.

PMID- 8575206
TI  - Structures of prion proteins and conformational models for prion diseases.

PMID- 8575207
TI  - The folding intermediate concept of prion protein formation and conformational
      links to infectivity.

PMID- 8575208
TI  - Cell biology of the prion protein.

PMID- 8575209
TI  - Transgenetics and gene targeting in studies of prion diseases.

PMID- 8575210
TI  - Introduction to the E2F family: protein structure and gene regulation.
AB  - E2F is a heterodimer composed of two partners, such as E2F1 and DP1. Although
      E2F1 can bind DNA as a homodimer and increase promoter activity, optimal DNA
      binding and transcriptional activity occurs in the heterodimeric form. A model
      (Fig. 3) for the involvement of E2F activity in cell growth control that
      incorporates viral oncoproteins, positive regulators of cell growth (cyclins) and
      negative regulators of cell growth (tumor suppressor proteins) can now be
      advanced. Each aspect of this model is addressed in subsequent chapters of this
      book. It is likely that binding of growth-suppressing proteins, such as Rb, can
      inhibit the transactivation potential of E2F1, either by blocking the interaction
      of E2F1 with a separate component of the transcription complex or by bringing a
      repressor domain to the transcription complex (Flemington et al. 1993; Helin et
      al. 1993; Weintraub et al. 1992; Zamanian and La Thangue 1993; Zhu et al. 1993).
      Phosphorylation or sequestration of Rb by viral oncoproteins can free E2F. The
      influence of viral oncoproteins on E2F activity and the regulation of the
      different E2F complexes is the focus of the contributions by Cobrinik and by
      Cress and Nevens. The interaction of the free E2F induces a bend in the DNA that
      may also play a role in transactivation, perhaps by bringing proteins (such as an
      Sp1 or CCAAT family member) separated by distance on the promoter DNA into
      contact (Huber et al. 1994). Because E2F target genes encode proteins critical
      for cell growth, deregulation of E2F activity can have severe consequences, such
      as apoptosis or uncontrolled proliferation. The effect of altered expression of
      E2F activity on the cell cycle and on tumorigenicity is the focus of the
      contribution by Adams and Kaelin. Finally, a comparison of E2F to the genetically
      well-characterized factors that regulate G1/S phase transcription in yeast is the
      subject of the chapter by Breeden. This volume concludes with Farnham's summary
      of the rapid gains in knowledge concerning the E2F gene family that have been
      made in the past several years and provides a series of questions and lines of
      investigation that will be the focus of future studies.

PMID- 8575211
TI  - Conclusions and future directions.

PMID- 8575212
TI  - Regulatory interactions among E2Fs and cell cycle control proteins.

PMID- 8575213
TI  - Use of the E2F transcription factor by DNA tumor virus regulatory proteins.

PMID- 8575214
TI  - The cellular effects of E2F overexpression.
AB  - The product of the retinoblastoma tumor-suppressor gene (RB) is a ubiquitously
      expressed, 105-kDa nuclear phosphoprotein (pRB). The pRB protein negatively
      regulates the cellular G1/S phase transition, and it is at this point in the cell
      cycle that it is thought to play its role as a tumor suppressor. The growth
      inhibitory effects of pRB are exerted, at least in part, through the E2F family
      of transcription factors. This chapter reviews the insights into the mechanism of
      action of the E2F family members that have been obtained through overexpression
      studies. Studies in RB-/- SAOS-2 cells have provided evidence in support of the
      hypothesis that the E2F family members are negatively regulated by pRB and the
      related protein p130. In particular, the results obtained are consistent with the
      earlier biochemical data which suggested that E2F1 is regulated primarily by pRB,
      and E2F4 by p130. Results relating to p107 are also discussed. Consistent with
      the proposed role of pRB and E2F1 as coregulators of entry into S phase,
      experiments have demonstrated that overexpression of E2F1 is sufficient to
      override the cell cycle arrests caused by serum deprivation of fibroblasts or
      transforming growth factor-beta (TGF-beta) treatment of mink lung epithelial
      cells. However, at least in the case of the serum deprivation induced arrest, the
      ultimate result of E2F1 overexpression is death by p53-dependent apoptosis. In
      light of this and other data, a model is discussed as to how functional
      inactivation of pRB and p53 might cooperate to promote tumorigenesis. A number of
      studies have demonstrated the oncogenic potential of E2F family members, at least
      under certain conditions. This is, again, in keeping with the notion that these
      proteins play a critical role in controlling proliferation.

PMID- 8575215
TI  - Start-specific transcription in yeast.

PMID- 8575216
TI  - Allergic reactions to nonrubber products by testing with rubber mixes. Part II:
      The mercapto mix.

PMID- 8575217
TI  - Pityriasis rosea.

PMID- 8575218
TI  - Tungiasis.

PMID- 8575219
TI  - Neonatal scabies.
AB  - Between 1981 and 1991, eleven infants (ranging in age from 2 to 9 months) were
      hospitalized in our department for evaluation of microscopically verified scabies
      infestations. Six presented signs of Norwegian scabies. All of the latter infants
      had been treated (prior to the scabies infestation) for long periods with topical
      steroids, in most cases for lesions suggestive of atopic dermatitis. We believe
      that the occurrence of the Norwegian form in these newborns was due to localized
      steroid-induced suppression of the normal immune response.

PMID- 8575220
TI  - Image analysis of nail fold capillaries in patients with Raynaud's phenomenon.
AB  - Videograph images of nail fold capillaries in patients with Raynaud's phenomenon
      were analyzed, and capillary patterns were defined using standardized canonical
      discriminant analysis. Of sixty-eight patients with Raynaud's phenomenon, forty
      nine (72 percent) showed a systemic sclerosis pattern and nineteen (28 percent)
      showed a normal pattern. The systemic sclerosis type capillary pattern
      significantly correlated not only with secondary Raynaud's syndrome but also with
      sclerodactyly, telangiectasia, and antinuclear antibody. This study confirms the
      value of nail fold capillary microscopy as a noninvasive technique for the
      examination of the cutaneous microcirculation in vivo. We should continue to
      evaluate the patients with Raynaud's phenomenon who showed systemic sclerosis
      pattern abnormality to determine if these patients would show a progression to
      systemic sclerosis or not.

PMID- 8575221
TI  - Lipoid proteinosis: clinical, histologic, and ultrastructural investigations.
AB  - The case of a 12-year-old boy with lipoid proteinosis is reported. Physical
      examination revealed long-standing varicella-like scars and areas of
      hyperpigmentation on the face and upper limbs with no evidence of
      photosensitivity, hoarseness, small papules along the free margins of eyelids,
      tongue firmness with short frenulum, and widespread papular lesions of the oral
      cavity. Histologic and ultrastructural examination revealed the characteristic
      skin changes: pink, hyaline-like, strongly periodic acid-Schiff-positive material
      in the dermis, surrounding blood vessels, and sweat glands; thin (30 to 35 nm)
      collagen fibrils interspersed in abundant amorphous material; blood vessels
      surrounded by thickened, multilayered basement membranes, in which layers of
      typical, homogeneous basement membrane material were alternating with
      electronlucent areas filled by various amounts of thin, cross-striated fibrils,
      arranged perpendicularly. These findings are of great interest since they show a
      complex relationship between type IV and type III-like collagen components.

PMID- 8575222
TI  - Bullous pemphigoid: persistent lesions of eczematous/urticarial erythemas.
AB  - Two patients with bullous pemphigoid presented with pruritic eczematous or
      urticarial eruptions on the trunk. These nonbullous lesions had persisted
      throughout the course of disease with no blistering lesions for more than two
      years in each patient.

PMID- 8575223
TI  - Treatment of recalcitrant warts using the pulsed dye laser.
AB  - Recalcitrant warts are a common therapeutic problem. We used the 585 nm pulsed
      dye laser to treat flat, common, plantar/palmar, and periungual warts that had
      failed to respond to keratolytic or destructive therapy. Flat warts were most
      responsive, but all wart types had a significant response to this benign
      treatment modality.

PMID- 8575224
TI  - Mal de Meleda.
AB  - A case of mal de Meleda originating in Chile is reported. The patient had no
      history of consanguinity and cases could not be detected in four generations of
      the patient's family. The palmoplantar keratoderma was progrediens and
      transgrediens, with distant hyperkeratotic plaques of the knees and elbows. The
      nails, hair, and teeth were normal.

PMID- 8575225
TI  - Unusual abdominal location of a dermal cylindroma.
AB  - Cylindromas are rare benign adenexal tumors that classically arise on the head
      and neck, thus earning the name of turban tumor. They are usually benign, but may
      be multiple and recurrent. A 78-year-old woman noted an abdominal cylindroma, an
      unusual presentation of this rare cutaneous tumor. The clinical presentation,
      histologic characteristics, and variations of the dermal cylindroma are reviewed.

PMID- 8575226
TI  - Control and research on schistosomiasis in China.

PMID- 8575227
TI  - Current treatment of vitiligo in China.

PMID- 8575228
TI  - The mechanism of clinical effectiveness of human fetal liver cell transfusion.

PMID- 8575229
TI  - Effects of antisense epidermal growth factor and its receptor retroviral
      expression vectors on cell growth of human pancreatic carcinoma cell line.
AB  - A 150 bp epidermal growth factor (EGF) cDNA fragment and a 1024 bp epidermal
      growth factor receptor (EGFR) cDNA fragment were inserted into 5.05 kb pBabe-puro
      retroviral vectors between BamH I and EcoR I sites in 3'-5' and/or 5'-3'
      orientation. The vectors were ligated with EGF and EGFR fragments by T-4 Ligase.
      The recombinant retroviral vectors were then packaged with packaging cell line
      PA317 through calcium phosphate mediated transfection. The viral supernatant of
      transfected PA317 cell lines were used to infect the human pancreatic carcinoma
      cell line PC-7. The resultant transformant cell lines: PC-7/AS-EGF, PC-7/S-EGFR,
      PC-7/AS-EGFR and PC-7/pBabe were tested for their endogenous EGF and EGFR mRNA
      expressions, cell growth rate, 3H-TdR incorporation rate, soft agar colony
      formation and tumorigenicity in nude mice. The results showed that there were
      noticeable inhibitions of cell growth, 3H-TdR incorporation rate, soft agar
      colony formation and tumorigenicity in nude mice in PC-7/AS-EGF and PC-7/AS-EGFR
      transformant cell lines. The endogenous EGF mRNA expression was blocked in PC
      7/AS-EGF cell line and the endogenous EGFR mRNA was significantly down-regulated
      in PC-7/AS-EGFR cell line.

PMID- 8575230
TI  - Duck hepatitis B virus model for screening of antiviral agents from medicinal
      herbs.
AB  - The effects of the extracts of 20 Chinese medicinal herbs and an antiviral drug
      foscarnet on duck hepatitis B virus (DHBV) endogenous DNA polymerase (DNAp)
      activity were compared. The extracts of P. urinaria showed a dose-dependent
      inhibition on DHBV DNAp. And those of other herbs showed little inhibition
      effect. Primary duck hepatocyte (PDH) cultures were used for evaluating effects
      of the extract of P. urinaria, foscarnet and acyclovir (ACV) on DHBV, and all the
      drugs or the extracts showed inhibition of DHBV DNA replication. Furthermore, in
      vivo trials were carried out. Peking ducks infected with LJ-76 strain of DHBV
      were treated with the extract of P. urinaria or ACV and compared with placebo
      treated control ducks. The treatment results in the loss or reduction of
      circulating viral DHBV DNA and DHBsAg.

PMID- 8575231
TI  - Effect of partial pressure on solubility of isoflurane in blood.
AB  - The effect of partial pressure of isoflurane on its solubility in blood of
      different haematocrit was determined at different isoflurane partial pressures,
      using a syringe--flask method and gas chromatography with blood from one donor.
      The solubility of isoflurane decreased with increasing blood haematocrit (39.5%,
      51.9% and 61.9%) and isoflurane partial pressure from 1 MAC to 4 MAC. The
      solubility in 50% and 60% haematocrit blood at 2, 3 and 4 MAC was significantly
      different from the solubility in normal blood at 1 MAC (P < 0.05). We conclude
      that the solution of isoflurane in blood (especially in high haematocrit blood)
      does not obey Henry's law.

PMID- 8575233
TI  - Radiofrequency catheter ablation of ventricular tachycardia in 26 patients.
AB  - Electrophysiology study and radiofrequency catheter ablation (RFCA) were
      performed in 26 patients with refractory sustained ventricular tachycardia (VT).
      After induction of VT, 12-lead electrocardiogram (ECG) was recorded and QRS
      morphology and axis of induced VT were studied to identify the origin of VT. The
      precise site of VT origin were localized by pace mapping and activation mapping
      carefully. RF energy was delivered through a big-tip deflectable electrode
      catheter when the earliest site of endocardial activation and a high-frequency
      and low-amplitude potential of Purkinje fiber, preceding surface QRS by more than
      25 ms, were identified and/or a pace map was obtained showing identical QRS
      complexes in at least 11 of 12 ECG leads. VTs were ablated successfully in 24 of
      26 patients (success rate was 92%). For successful ablation, it is essential that
      the pace map QRS morphology in 12 leads should be identical with that in
      spontaneous or induced VT as far as possible in performing pace mapping. Pace
      mapping is safe, simple and has no unfavourable effect hemodynamics although it
      takes longer time. Activation mapping takes shorter time and has a high success
      rate. QRS configuration in spontaneous VT can help to localize the site of VT
      origin. Deliberate mapping at the site suggested to bo the origin of VT by
      surface ECG can shorten the duration of mapping and increase the success rate of
      RFCA. RFCA of VT in patients without structural heart disease is effective, safe,
      and has a high success rate, so it may be considered as an early therapy for
      these patients.

PMID- 8575232
TI  - Quantitation of P53 protein expression in gastrointestinal smooth muscle tumors.
      Clinicopathological correlation and prognostic significance.
AB  - Quantitative analysis of P53 protein expression was performed on paraffin
      embedded tissues from 55 smooth muscle tumors of the gastrointestinal tract,
      using immunofluorescence and flow cytometry. No positive expression was found in
      normal smooth muscle tissues of the gastrointestinal tract. Over-expression of
      P53 gene was found in a significantly higher proportion in leiomyosarcomas (90%)
      and potentially malignant smooth muscle tumors (75%) as compared to leiomyomas
      (14%) (P < 0.005). The quantitation of P53 expression was found to be
      progressively enhanced in the sequence from leiomyoma through potentially
      malignant smooth muscle tumor to leiomyosarcoma (P < 0.005). It was markedly over
      expressed when the mitotic counts ranged from one to more than one per 10 high
      power fields (P < 0.005) or the mild cytologic atypia was found (P < 0.005). The
      five-year survival rate was significantly higher in patients with low-expression
      of P53 than in those with over-expression of P53 (P < 0.005). It was suggested
      that P53 over-expression might be associated with the transformation of leiomyoma
      into leiomyosarcoma and could be used as an objective parameter in distinguishing
      the malignant from the benign and predicting the prognosis of patients with
      smooth muscle tumors of the gastrointestinal tract.

PMID- 8575234
TI  - Effect of perindopril and metoprolol on left ventricular hypertrophy and
      performance in essential hypertension.
AB  - The effects of perindopril and metoprolol on left ventricular hypertrophy (LVH)
      and function were studied in 47 essential hypertensive patients with LVH.
      Previous antihypertensive drugs were discontinued for at least 2 weeks, after
      which patients were randomly divided into 2 groups. 25 subjects were treated with
      perindopril 4 to 8 mg once daily in the morning (Group A) and 22 subjects with
      metoprolol 25 to 62.5 mg twice daily (Group B). The subjects were evaluated
      before and after 4 and 8 weeks of treatment by use of echocardiography. Before
      treatment LV mass indexes (LVMI) of two groups were respectively 143.2 +/- 21.3
      g/m2 and 140.6 +/- 23.7 g/m2 (P > 0.05). In Group A, reduction of LVMI occurred
      after 4 weeks of treatment, and more pronounced after 8 weeks (from 143.2 +/-
      21.3 g/m2 to 126.6 +/- 15.3 g/m2, P < 0.001), whereas reduction of LVMI occurred
      only after 8 weeks in Group B (from 140.6 +/- 23.7 g/m2 to 133.4 +/- 13.2 g/m2, P
      < 0.001). In addition, there was a significant (P < 0.05) difference in LVMI
      between the two groups after 8 weeks. LV systolic function remained unchanged,
      whereas E/A increased significantly (P < 0.001) in two groups after 8 weeks. In
      conclusion, antihypertensive treatment with perindopril and metoprolol induced a
      significant regression of LVH associated with improvement in LV diastolic
      performance. Perindopril, compared with metoprolol, was more effective in
      reversing LVH.

PMID- 8575235
TI  - Effect of antihydatid drugs on carbohydrate metabolism of metacestode of
      echinococcus granulosus.
AB  - A biochemical some enzymes of glycolysis and a partial reversed tricarboxylic
      acid cycle together with hydrolytic enzymes in the cyst wall of Echinococcus
      granulosus was carried out. Lactate dehydrogenase (LDH), pyruvate kinase (PK),
      phosphoenolpyruvate carboxykinase (PEPCK), and adenosine triphosphatase (ATPase)
      showed their high level of activity, suggesting that the proliferation of E.
      granulosus cyst wall is an energy-dependent process and the major pathways for
      glucose metabolism is glycolysis. Treatment of E. granulosus-infected mice with
      mebendazole and albendazole resulted in marked inhibition of PK, PEPCK and ATPase
      of E. granulosus cyst wall, whereas praziquantel had no effect, indicating that
      PK, PEPCK, and ATPase might be chemotherapeutic targets and the differences in
      the inhibitory effects might account for the efficacy of the three antihydatid
      drugs.

PMID- 8575237
TI  - Radiologic manifestations of osteopetrosis.
AB  - The clinical radiologic manifestations of 8 patients with osteopetrosis (4 males
      and 4 females) are analyzed. Six of the cases are benign. The pathologic basis
      for the radiologic manifestations is discussed, and a classification is
      suggested. "Broom-like" metaphyses, metaphyses containing three or four dense
      layers of bone, and ossification of soft tissues around joints were found and
      differential diagnosis was made.

PMID- 8575236
TI  - Multimodality therapy including surgical resection for limited small cell lung
      cancer.
AB  - From 1975 through 1990, 199 patients with limited small cell lung cancer (LSCLC)
      were subjected to multimodality treatment including surgical resection combined
      with chemotherapy or chemoradiotherapy in our department. The median
      postoperative survival time of the 199 patients was 39 months, and the 5-year
      survival rate was 26%, which was decreased with increase of tumor-stage. In
      comparison of the survival time of patients in Stage I and those in Stage IIIa,
      there was a significant difference (P < 0.01). There were no significant
      differences in survival rate of 3 and 5 years between the patients receiving
      chemotherapy prior to or after surgical resection. The improvement in survival
      was documented by surgical resection combined with chemotherapy or
      chemoradiotherapy for LSCLC. The effect of multimodality treatment is correlated
      with tumor P-TNM staging, the involvement of lymph node, especially that of the
      mediastinal lymph node, is a negative factor influencing the prognosis. Surgical
      resection is an initial management, followed by chemotherapy or chemoradiotherapy
      may be indicated in LSCLC patients of Stage I, Stage II and some Stage IIIa as
      the cancer can be resected completely.

PMID- 8575238
TI  - Ischemia and reperfusion reduce the endogenous basic fibroblast growth factor (bF
      GF) in rat skeletal muscles.
AB  - Polyclonal antibodies directed against human recombinant basic fibroblast growth
      factor (bFGF) were used in immunohistochemical studies to localize this growth
      factor in normal and wounded rat skeletal muscles. bFGF immunoreactivity was
      found mainly in the extracellular matrix, primarily in the endomysium, including
      the heparin-containing basal lamina and also in the capillary basal membrane of
      both normal and wounded muscles, however the signal intensity was much stronger
      in normal muscles. After 4-hour ischemia, about 40% of skeletal muscle fibers
      lost their bFGF immunoreactivity. Muscles which experienced 4-hour ischemia and
      24 reperfusion had only a weaker bFGF immunoreactivity. The pathological results
      supported the concept of destroyed cell connection and fiber necrosis in ischemia
      and reperfused muscles. The mechanisms involved in this reduced concentration of
      bFGF in wounded muscles included oxygen radical activation, inflammatory response
      and reduced secretion of endogenous bFGF. These results were only partially
      compatible with the established mitogenic role of this protein and suggested that
      a reduction of endogenous FGF may partly contribute to a delay in wound healing.

PMID- 8575239
TI  - Suppurative knee arthritis following acute osteomyelitis of the femur detected by
      magnetic resonance.

PMID- 8575240
TI  - The destruction of bone by neutrophils.

PMID- 8575241
TI  - Post-stroke antihypertensive treatment study. A preliminary result.
AB  - Post-stroke Antihypertensive Treatment Study (PATS) was a randomized, double
      blind and placebo-controlled trial, which aimed at determining whether
      antihypertensive treatment could reduce the risk of fatal and nonfatal stroke
      incidence in patients with a history of stroke or transient ischemic attack
      (TIA). 5,665 patients were randomized by a sealed envelope system. Systolic blood
      pressure (SBP) ranged from 80 to 280 mm Hg and diastolic (DBP) from 50 to 150
      mmHg. The average SBP was 154 mmHg and average DBP 93 mmHg. The mean age was 60
      years. Among the patients, women accounted for 28%. In 71% the latest stroke was
      ischemic. Average follow-up approximated to 2 years. The three-year average SBP
      was 149 mmHg for the placebo group and 144 mmHg for the indapamide treatment
      group, and the three-year DBP was 89 mmHg and 87 mmHg respectively. The three
      year first incidence of fatal and nonfatal stroke was 12.3 per 100 patients
      placebo treatment and 9.4 per 100 with indapamide. The relative risk by
      proportional hazards regression analysis was 0.71 (P = 0.0009). For deaths from
      all causes, the relative risk was 0.91. (P > 0.05). The findings of this trial
      indicate that in patients with a history of stroke or TIA, blood pressure
      reduction of 5/2 mmHg with 2.5 mg indapamide reduced the first incidence of fatal
      and nonfatal stroke by 29%, with three-year absolute benefit of 29 events per
      1000 participants.

PMID- 8575242
TI  - Chromosome 'painting' in plants - a feasible technique?
AB  - It is shown that chromosome painting is as yet not possible for plants with very
      complex genomes, neither intra- nor interspecific. The reasons are inefficient
      blocking of dispersed repetitive sequences and insufficient signal intensity of
      short unique sequences. Future perspective are indicated.

PMID- 8575243
TI  - Cell cycle related behavior of a chromosomal scaffold protein in MDCK epithelial
      cells.
AB  - Because the mechanisms that govern mitosis are a key to the understanding of cell
      growth, the proteins associated with chromosomes specifically during this phase
      have received thorough attention. In the present work we report an Mr58000
      protein in MDCK epithelial cells, recognized by a monoclonal antibody (LFM-1)
      that decorates chromosomes during M-phase. Cell fractionation methods followed by
      immunoblotting and immunofluorescence showed that this protein is associated with
      the nuclear fraction. Biochemical extraction procedures on isolated metaphase
      chromosomes from nocodazole-synchronized cells indicated that the Mr58000 protein
      behaves as a chromosomal scaffold protein, that is, it remains in the pellets
      after high salt (2M NaCl) or 3'-5' diiodosalicylic acid treatments, even in DNAse
      pre-digested samples. In addition, confocal microscopy of those chromosomes
      revealed the LFM-1 epitopes distributed on the external surface and the axis of
      chromatids. Parallel analysis of interphase nuclei revealed LFM-1 epitopes inside
      G1-, but excluded from G2-phase nuclei. These results were independently
      confirmed on nuclei sorted by flow cytometry and in cell populations synchronized
      by release of G1-/S-phase hydroxyurea arrest. The Mr58000 and a minor Mr38000
      protein (which was enriched only in mitotic chromosomes of synchronized cells)
      were analyzed by Edman degradation. They shared the sequence at the amino
      terminal end but failed to show total homology with known proteins. These results
      suggest that LFM-1 antigens fit some of the predictions of the licensing factor
      model, and may have a role in cell cycle dependent events.

PMID- 8575245
TI  - Chromosomal distribution of the hamster intracisternal A-particle (IAP)
      retrotransposons.
AB  - The retrotransposon-like elements of the intracisternal A-particle (IAP)
      sequences occur in about 900 copies per haploid hamster cell genome. By applying
      the fluorescent in situ hybridization (FISH) technique and four different, cloned
      segments of the IAP element as hybridization probes, these elements were found to
      be distributed in specific patterns over many of the 44 hamster chromosomes. The
      hybridization patterns were very similar regardless of whether all four probes or
      only the IAPI probe carrying the long terminal repeat (LTR) region were used. The
      IAP elements were found most abundantly, though not exclusively, on the short
      arms of at least 12 of the autosomes. Of the sex chromosomes, the shorter Y
      chromosome was stained on both arms, and the X chromosome on one arm by the IAP
      probes. Primary Syrian hamster cells, the established Syrian hamster cell line
      BHK21, and the adenovirus type 12 (Ad12)-transformed BHK21 cell line T637 yielded
      very similar results. In Chinese hamster ovary (CHO) or 3T3 mouse cells, signals
      could not be elicited by FISH using the Syrian hamster IAP probes. On Southern
      blots, the DNAs from these cell lines hybridized very weakly, if at all, to the
      IAP sequences. Thus, IAP sequences were retroposed after Syrian hamster and mouse
      or Syrian and Chinese hamsters had diverged in evolution.

PMID- 8575244
TI  - Introduction of a DNA methyltransferase into Drosophila to probe chromatin
      structure in vivo.
AB  - The dam DNA methyltransferase gene from Escherichia coli was introduced into
      Drosophila in order to probe chromatin structure in vivo. Expression of the gene
      caused no visible defects or developmental delay even at high levels of active
      methylase. About half of each target site was found to be methylated in vivo,
      apparently reflecting a general property of chromatin packaged in nucleosomes.
      Although site-specific differences were detected, most euchromatic and
      heterochromatic sites showed comparable degrees of methylation, at least at high
      methylase levels. Methylase accessibility of a lacZ reporter gene subject to
      position-effect variegation throughout development was only slightly reduced,
      consistent with studies of chromatin accessibility in vitro. Silencing of lacZ
      during development differed from silencing of an adjacent white eye pigment
      reporter gene in the adult, as though chromatin structure can undergo dynamic
      alterations during development.

PMID- 8575246
TI  - On the origin of lateral asymmetry.
AB  - Lateral asymmetry refers to unequal fluorescent intensity between adjacent
      regions of sister chromatids. It has been observed in the centromeric regions of
      mitotic chromosomes of mouse or human origin when cells are grown in 5-bromo-2'
      deoxyuridine (BrdU) for a single round of DNA synthesis. The chromosome
      orientation fluorescence in situ hybridization (CO-FISH) technique was used with
      pseudodiploid mouse cells to show that the regions of asymmetrical brightness
      coincide with major satellite repetitive DNA, and that the more heavily BrdU
      substituted chromatid is the one that fluoresces less brightly. These
      observations support a 20 year old hypothesis on the origin of lateral asymmetry.
      Other observations suggest that differential loss of DNA from the heavily
      substituted chromatid also contributes to lateral asymmetry.

PMID- 8575247
TI  - Comparative karyology and evolution of the Amazonian Callithrix (Platyrrhini,
      Primates).
AB  - Chromosomal studies in three species of Amazonian Callithrix (2n=44) and data in
      the literature show that this group is karyomonotypic. Moreover, it is
      characterized by the presence of abundant heterochromatic regions, unlike the
      situation in congeneric forms of Callithrix of the Atlantic coast with 2n=46, and
      by the presence of a highly repetitive, exclusive DNA component, with a basic
      repeat motif of 1528bp. Karyotypic comparisons with other Callitrichids and an
      outgroup species showed that Callitrichids are karyologically conserved and
      explained several rearrangements that had presumably occurred during their
      phyletic radiation. Analyses of karyologic data enabled the construction of two
      alternative phylogenetic topologies. The lack of derived homoeologies, common to
      all members of the genus Callithrix grouped at present, and the fact that
      Amazonian species were more similar to Cebuella pygmaea (2n=44) than to their
      congeneric forms with 2n=46 suggested that species at present included in the
      Amazonian Callithrix should be grouped with C. pygmaea.

PMID- 8575248
TI  - A monoclonal antibody against DNA topoisomerase II labels the axial granules of
      Pleurodeles lampbrush chromosomes.
AB  - By immunizing Balb/c mice with oocyte nuclei of Pleurodeles waltl we obtained a
      monoclonal antibody, mAb 4A6, that labels distinct globular domains of the
      lampbrush chromosomal axes of Pleurodeles. These domains are found at
      corresponding sites of homologous chromosomes, often at telomeric and putative
      centromeric regions, and appear to be devoid of DNA. Because of these
      characteristic features it is most likely that the mAb 4A6-positive domains
      correspond to the central part of the "axial granules" of urodelan lampbrush
      chromosomes. In immunoblotting analyses mAb 4A6 reacts with a nuclear antigen of
      approximately Mr 180000 and a structurally nonrelated cytoplasmic protein of Mr
      98000, which was not characterized any further. Comparative immunofluorescence
      and immunoblotting studies with mAb 4A6 and an antiserum against DNA
      topoisomerase II (topo II) as well as immunodepletion experiments demonstrated
      that the nuclear 4A6 antigen is topo II. Our results indicate that topo II is not
      a constituent of a continuous, loop-anchoring scaffold in lampbrush chromosomes
      of Pleurodeles but, rather, is restricted to the axial granules.

PMID- 8575250
TI  - Localization of DNA in the condensed interphase chromosomes of Euglena.
AB  - The localization of DNA in the condensed interphase chromosomes of Euglena was
      determined by immunoelectron microscopy. Deposits of gold particles that
      coincided with the localization of DNA followed threads that corresponded to the
      chromatin fibers. The threads were 55-80nm in diameter and were assumed to be
      supersolenoids. The localization of gold deposits on chromosomes that had been
      sectioned in various directions suggested that the chromatin fibers coiled around
      the surface of chromosomes, with a wide central axial region of the chromosomes
      remaining free of DNA. These findings are discussed in relation to current models
      of chromosomal structure.

PMID- 8575249
TI  - The MAN antigens are non-lamin constituents of the nuclear lamina in vertebrate
      cells.
AB  - The characterization of the human antiserum designated MAN has led to the
      identification of a subset of non-lamin proteins that are exclusively located at
      the nuclear periphery in all vertebrate cell types examined, from human to fish.
      Immunoreactive protein species were shown to comprise three major polypeptides of
      Mr 78000, 58000 and 40000. These antigens co-partitioned with the nuclear lamina
      during in situ isolation of nuclear matrices from lamin A/C-positive and 
      negative mammalian cells. Using double immunofluorescence, the spatial
      relationship of MAN antigens to type-A and type-B lamins was further examined
      throughout the cell cycle of lamin A/C-positive mammalian cells. In interphase
      HeLa and 3T3 cells, MAN antigens colocalized with both types of lamins at the
      periphery of the nucleus, but were absent from intranuclear foci of lamin B. As
      HeLa cells proceeded into mitosis, MAN antigens were seen to segregate from
      lamins A/C and coredistribute with lamin B. Lamins A/C disassembled during late
      prophase/early prometaphase and reassociated with chromatin in
      telophase/cytokinesis. In contrast, MAN antigens and lamin B dispersed late
      during prometaphase and reassembled on chromosomes in anaphase. Altogether, our
      data suggest that MAN antigens may play key functions in the maintenance of the
      structural integrity of the nuclear compartment in vertebrate cells.

PMID- 8575252
TI  - The Molecular Biology and Pathology of Elastic Tissues. Symposium proceedings.
      Nairobi, Kenya, 1-3 November 1994.

PMID- 8575251
TI  - A male-specific nuclease-resistant chromatin fraction in the mealybug Planococcus
      lilacinus.
AB  - In mealybugs, chromatin condensation is related to both genomic imprinting and
      sex determination. The paternal chromosomal complement is condensed and
      genetically inactive in sons but not in daughters. During a study of chromatin
      organization in Planococcus lilacinus, digestion with micrococcal nuclease showed
      that 3% to 5% of the male genome is resistant to the enzyme. This Nuclease
      Resistant Chromatin (NRC) apparently has a nucleosomal organization. Southern
      hybridization of genomic DNA suggests that NRC sequences are present in both
      sexes and occur throughout the genome. Cloned NRC DNA is A+T-rich with stretches
      of adenines similar to those present in mouse alpha-satellite sequences. NRC DNA
      also contains sequence motifs that are typically associated with the nuclear
      matrix. Salt-fractionation experiments showed that NRC sequences are matrix
      associated. These observations are discussed in relation to the unusual
      cytological features of mealybug chromosomes, including the possible existence of
      multiple centres of inactivation.

PMID- 8575253
TI  - Catalytic properties and structural components of lysyl oxidase.
AB  - Key aspects of the biosynthesis and catalytic specificity of lysyl oxidase (LO)
      have been explored. Oxidation of peptidyl lysine in synthetic oligopeptides is
      markedly sensitive to the presence of vicinal dicarboxylic ami/no acid residues.
      Optimal activity is obtained with the -Glu-Lys- sequence within a polyglycine 11
      mer, whereas the -Lys-Glu- sequence is much less efficiently oxidized. The -Asp
      Glu-Lys- sequence is a very poor substrate, although this sequence is oxidized in
      type I collagen fibrils. These results are considered in the light of a model
      requiring collagen to be assembled as fibrils prior to oxidation by LO. An in
      vitro system for the expression of catalytically active LO has been devised.
      Deletion or inclusion of the cDNA coding for the propeptide region in the
      expressed construct results in apparently identical, catalytically active enzyme
      products, indicating the lack of essentiality of this region for active enzyme
      production. These effects are considered with respect to the conservation of the
      amino acid sequence of LO produced by different species.

PMID- 8575254
TI  - The structure and function of fibrillin.
AB  - Fibrillin is a very large molecule whose primary structure is now known from the
      cloning and sequencing of 10 kb of cDNA. Immunohistochemical results suggest that
      one of the functions of fibrillin molecules is to contribute to the structure of
      the microfibril. The importance of fibrillin as a structural macromolecule has
      been demonstrated by the identification of the gene for fibrillin (FBN1) as the
      disease-causing gene in Marfan's syndrome. While it is clear that fibrillin
      contributes to the structure of the microfibril, it is not known whether
      fibrillin molecules self-assemble or whether fibrillin interacts with other
      molecules in order to form microfibrils. In order to investigate whether
      particular domains of fibrillin are important to the assembly of the microfibril
      and to specify domains that participate in interactions with other proteins, we
      have produced recombinant fibrillin 1 peptides in human cells and used them in
      studies described here. Additionally, new information regarding the 5' end of
      FBN1 has been obtained from studies investigating promoter activity, and
      potential proteolytic cleavage sites have been identified in the N- and C
      terminal domains.

PMID- 8575255
TI  - Elastin gene mutations in transgenic mice.
AB  - We have constructed several rat tropoelastin minigene recombinants encoding the
      complete sequence of rat tropoelastin, two isoforms of rat tropoelastin and a
      truncated tropoelastin lacking the domains encoded by exons 19-31 of the rat
      gene. Coding and non-coding domains in all these recombinants were placed under
      the transcriptional control of 3 kb of the promoter domain of the rat
      tropoelastin gene. These minigenes were used to prepare a total of 28 separate
      founder lines of transgenic mice. A species-specific reverse-transcriptase
      polymerase chain reaction (RT-PCR) assay was established to demonstrate the
      synthesis of rat and mouse tropoelastin mRNA in several tissues obtained from
      both neonatal and adult transgenic mice. Thermolytic digestion of insoluble
      elastin isolated from several neonatal mouse tissues revealed the presence of rat
      tropoelastin peptides in progeny from all those founder mice in which detectable
      levels of rat tropoelastin mRNA were noted. Phenotypic and histopathological
      assessment of transgenic and non-transgenic animals revealed the development of
      two diverse elastic tissue disorders. The progeny of two separate founder lines
      overexpressing the rat tropoelastin isoform lacking exon 33, developed an
      emphysematous phenotype in early adulthood. In contrast, transgenic mice, in
      which expression of the truncated rat tropoelastin minigene lacking exons 19-31
      had been observed, died of a ruptured ascending aortic aneurysm. Tropoelastin
      gene mutations, therefore, will result in heritable disorders of elastic tissue.
      Moreover, different mutations in the tropoelastin gene will be responsible for
      very different abnormalities in elastic tissue function.

PMID- 8575256
TI  - Elastic fibre assembly: macromolecular interactions.
AB  - To investigate the mechanisms behind elastic fibre assembly, we studied the
      molecular interactions between elastin and microfibrillar components using solid
      phase binding assays. Fibrillin 1, purified from tissue using reductive-saline
      extraction, showed no binding to microfibril-associated glycoprotein (MAGP) or
      tropoelastin. MAGP, however, was found to bind specifically to tropoelastin in a
      divalent-cation independent manner. Antibody inhibition studies indicated that
      the C-terminus of tropoelastin defined the interactive site with MAGP. MAGP and
      fibrillin were also substrates for transglutaminase, which may provide an
      important mechanism for stabilizing microfibrillar structure. In other studies we
      found that a major cross-linking region in elastin is formed through the
      association of domains encoded by exons 10, 19 and 25 of tropoelastin and that
      the three chains are joined together by one desmosine and two lysinonorleucine
      cross-links.

PMID- 8575257
TI  - The 67 kDa spliced variant of beta-galactosidase serves as a reusable protective
      chaperone for tropoelastin.
AB  - Numerous cell types express the 67 kDa galactolectin related to the alternatively
      spliced variant of beta-galactosidase. This 67 kDa protein, while present on cell
      surfaces, mediates cell contacts with elastin, laminin and collagen type IV. In
      elastin-producing tissues, the 67 kDa protein also co-localizes with
      intracellular tropoelastin and mature elastic fibres. We have established that
      this elastin binding protein (EBP) serves as a molecular chaperone for
      tropoelastin. The EBP binds this highly hydrophobic and unglycosylated ligand
      intracellularly, protecting it from intracellular self aggregation and premature
      proteolytic degradation, and mediates its orderly assembly upon the
      microfibrillar scaffold. While some of this protein is incorporated as a
      permanent component of elastic fibres, most of the EBP, after extracellular
      dissociation from its ligand, recycles back to the intracellular endosomal
      compartment and re-associates with the newly synthesized tropoelastin. We suggest
      that recycling of this reusable shuttle protein is imperative for the effective
      extracellular deposition of insoluble elastin.

PMID- 8575258
TI  - Elastin in lung development and disease.
AB  - Elastic fibres are present in lung structures including alveoli, alveolar ducts,
      airways, vasculature and pleura. The rate of lung elastin synthesis is greatest
      during fetal and neonatal development, and is minimal in the healthy adult. We
      have determined that glucocorticoids up-regulate fetal lung tropoelastin
      expression while concomitantly accelerating terminal airspace maturation. Because
      there is minimal turnover of elastin in healthy adult lung, the elastin
      incorporated into the lung early in development supports lung function for the
      normal lifespan. However, in the adult lung, in pathological circumstances such
      as emphysema or pulmonary fibrosis there may be reactivation of elastin
      expression. We have found in silica-induced pulmonary fibrosis that expression of
      tropoelastin is primarily increased in the walls and the septal tips of the
      alveolus, with modest increases in other compartments which normally express
      tropoelastin during development. This finding suggests that the mesenchymal cell
      of the alveolar wall increases tropoelastin expression during fibrotic disorders.
      In emphysema and fibrosis, elastin is present in abnormal-appearing, probably non
      functional, elastic fibres, suggesting that the adult lung cannot recapitulate
      the elastic fibre assembly mechanisms operative during normal lung growth.

PMID- 8575259
TI  - Elastin and mechanoreceptor mechanisms with special reference to the mammalian
      carotid sinus.
AB  - Light microscopic studies reveal that the carotid baroreceptor region in mammals,
      located at the origin of the internal carotid artery, has a preponderantly
      elastic structure and a thick tunica adventitia. Electron microscopy discloses
      the presence of sensory nerve endings within the parts of the tunica adventitia
      adjoining the preponderantly elastic zone of the internal carotid artery. Bundles
      of collagen fibres in the tunica adventitia form convolutions or whorls around
      the nerve terminals and often terminate on the surface of the elastic fibres or
      into the basement membranes of the neuronal profiles. It is concluded that the
      large content of elastic tissue in the tunica media of the baroreceptor region
      renders the vessel wall highly distensible to intraluminal pressure changes, and
      thereby facilitates transmission of the stimulus intensity to sensory nerve
      terminals. However, a change in the geometrical configuration of the bundles of
      collagen under the influence of elastic fibres may provide a better insight into
      the mechanisms of distortion of the baroreceptors related to and/or in contact
      with collagen fibres. In support of this is the demonstration of contact sites
      between collagen and elastic fibres.

PMID- 8575261
TI  - Elastin in systemic and pulmonary hypertension.
AB  - Increased elastin production and accumulation is a rapid and sensitive response
      to elevated vascular wall stress in both systemic and pulmonary hypertension.
      While initially protecting the vessel wall, these structural changes may in the
      longer term result in reinforcement of the hypertensive state and contribute to
      the persistence of the pathology of hypertension. Rapid responses apparently
      uncorrelated with increased elastin mRNA, at least in the case of systemic
      vessels, suggest novel mechanisms perhaps including increased efficiency of
      message translation or matrix accumulation of the protein. Investigations using
      in vitro organ and cell culture models have indicated a role for phospholipases
      and protein kinases, including protein kinase C, in stretch-induced elastin
      synthesis. In addition, tyrosine phosphorylation of membrane/sub
      membrane/cytoskeletal sensors, including focal adhesion kinase and members of the
      lipocortin family, have been shown to be important in this transduction
      mechanism. Because its turnover is normally very slow, additional vascular
      elastin accumulated during hypertensive episodes, together with its consequences
      for the physical properties of the vessel wall, may persist long after blood
      pressure is restored to normal levels. Thus, recent interest has been drawn to
      the possibility of achieving regression of accumulated matrix elastin by
      promoting turnover of this protein through activation of endogenous vascular
      elastase and collagenase activities.

PMID- 8575260
TI  - Skin elastic fibres: regulation of human elastin promoter activity in transgenic
      mice.
AB  - Elastic fibres form an extracellular network which provides elasticity and
      resilience to tissues such as the skin. To study the regulation of human elastin
      gene expression, we have developed a line of transgenic mice which harbour 5.2 kb
      of human elastin gene promoter region in their genome. This promoter is linked to
      the chloramphenicol acetyltransferase (CAT) reporter gene which allows
      determination of the expression of human elastin promoter in different tissues.
      The highest CAT activity was found in the lungs and aorta, tissues rich in
      elastin, while lower levels were detected in a variety of other tissues,
      including skin. Assay of CAT activity in the lungs of fetal and newborn animals
      revealed high activity which progressively declined during the postnatal period
      up to six months. Thus, there was evidence of tissue-specific and developmentally
      regulated expression of the human elastin promoter activity in these mice. These
      animals were then used to examine the expression of the elastin gene by a variety
      of factors which have previously shown to alter elastin gene expression, as
      determined at the mRNA or protein levels. First, injection of transforming growth
      factor beta 1 (100 ng) subcutaneously into the transgenic animals resulted in a
      time-dependent elevation of the promoter activity up to 10-fold after a single
      injection. Secondly, enhancement of the human elastin promoter activity by
      interleukin 1 beta injected subcutaneously resulted in an approximately 10-fold
      elevation of the CAT activity. Finally, subcutaneous injection of these animals
      with triamcinolone acetonide or dexamethasone, two glucocorticosteroids in
      clinical use, resulted in marked enhancement of human elastin promoter activity.
      Similar changes were noted in fibroblast cultures established from the transgenic
      animals. These data indicate that the 5.2 kb upstream segment of the human
      elastin gene contains cis-elements which allow tissue-specific and
      developmentally regulated expression of the human elastin promoter. Furthermore,
      this segment of the gene contains responsive elements to a variety of cytokines
      and pharmacological agents. Collectively, these data indicate that elastin gene
      expression in the skin in vivo can be regulated at the transcriptional level.

PMID- 8575262
TI  - Elastin in blood vessels.
AB  - Elastin fibres give blood vessels important rheological properties, such as the
      postsystolic elastic recoil. The age-dependent increase of Ca2+ and lipid
      content, and elastolytic degradation of the fibres progressively impairs their
      function and produces circulating elastin peptides. Their interaction with the
      elastin receptor on smooth muscle cells induces not only increased cell-elastin
      fibre adhesion and endothelium-dependent vasorelaxation but also the release of
      lytic enzymes and oxygen free radicals from monocytes penetrating the vascular
      wall during atherogenesis. The age-dependent 'uncoupling' of the receptor has
      been shown to be involved in the loss of Ca2+ homeostatic mechanisms and the
      progressive calcification of the vessel wall.

PMID- 8575264
TI  - Ultrastructure of elastin.
AB  - Almost all structural studies on elastin have been done in higher vertebrates, in
      which it is organized as an extracellular network of branched fibres which vary
      from fractions f microns to several microns in diameter. By conventional electron
      microscopy, elastin appears amorphous. By both freeze-fracture and negative
      staining on cryosections, it can be resolved as beaded filaments 5 nm in diameter
      forming a 3D meshwork that, upon stretching, becomes oriented in the direction of
      the force applied. This filamentous aggregation of elastin molecules is confirmed
      in vitro by the observation that its soluble precursor, tropoelastin, shows a
      strong tendency to associate into short 5 nm-thick filaments that, with time,
      become longer and aggregate into bundles of various dimensions. If chemically
      fixed and embedded, these aggregates appear amorphous and identical to natural
      elastin fibres. The tendency of tropoelastin to aggregate into 4-5 nm-thick
      beaded filaments, which then associate into 12 nm-thick filaments forming a 3D
      network, has been observed by atomic force microscopy for recombinant human
      tropoelastin. Therefore, the amorphous structure of elastin seems to be a
      technical artefact. Apart from elastin-associated microfibrils, which are always
      present at the periphery of growing elastic fibres and probably have a role more
      complex than being a scaffold for tropoelastin aggregation in vivo, the elastic
      fibres seem to be composed of several matrix constituents, which are different in
      different organs and change with age and in pathological conditions. This is
      demonstrated by immunocytochemical studies on ultrathin sections.

PMID- 8575263
TI  - Elastase in the prevention of arterial aging and the treatment of
      atherosclerosis.
AB  - Arterial aging is defined as the age-related structural and functional changes in
      arteries from the precapillary to the aortic level. These include atheromatous
      changes. Such changes can be estimated in medium-sized or larger arteries by
      clinical diagnostic studies, including B-mode echography of the carotid artery
      (thickening of the intima, plaque formation and increase in luminal diameter) and
      abdominal aorta (plaque formation and increase in luminal diameter). Doppler
      echography (pulse wave velocity; PWV) and autopsy studies. These changes include
      distension of the lumen, increased arterial wall thickness (which may be
      associated with atherosclerotic plaques) and decreased extensibility of the
      arterial wall. Since 1981, an anti-atherosclerotic drug containing porcine
      pancreatic elastase 1 (PPE1) has been used for the prevention of arterial aging
      and the treatment of atherosclerosis in elderly patients in Japan. So far, the
      age-related increase in PWV has been found to be lower in those who take PPE1
      than in controls. The atherosclerotic index of the carotid artery has also been
      found to be lower in subjects receiving PPE1 treatment than in control subjects.
      The pharmacological basis of PPE1 therapy, although paradoxical to the consensus
      opinion of the pathogenic role of elastase in western countries, is discussed
      with reference to data gathered in Japan. The pathomechanism of arterial aging
      and atherosclerosis, with special reference to elastin, is reviewed along with
      the presentation of some of our data.

PMID- 8575265
TI  - Interaction of tumour cells with elastin and the metastatic phenotype.
AB  - It is now well established that the interaction of tumour cells with elastin is
      important during invasion and metastasis. This is due to the fact that the
      elastin receptor complex is widely expressed by tumour cells and is overexpressed
      in highly metastatic variants. There is evidence that the elastin receptor
      complex is associated with a signal system involving G proteins, phospholipase C,
      the phosphoinositol cycle and protein kinase C. Therefore, activation of the
      elastin receptor system results in activation of protein kinase C-dependent
      cellular processes such as enzyme secretion and migration. Accordingly, soluble
      elastin can be used in vivo to interfere with tumour cell dissemination into
      elastin-rich tissues such as lung, skin or blood vessels. The importance of
      elastin-tumour cell interactions is emphasized by the observation that the 67 kDa
      receptor for laminin may well be identical to the 67 kDa elastin receptor of the
      elastin receptor complex. Interference with the function of this receptor system
      by the use of both laminin peptides and elastin ligands may provide the basis for
      a novel and more powerful antimetastatic intervention.

PMID- 8575266
TI  - A role for neutrophil elastase in solar elastosis.
AB  - Hairless (SKH-1) mice were mated with beige (C57BL/bb) mice to produce a hairless
      mouse deficient in neutrophil elastase (hhbb). These mice were exposed to 0.09 J
      UVB radiation for 5 months to see if neutrophil elastase was an important factor
      in the development of solar elastosis. Analysis of peritoneal neutrophils
      confirmed that the hhbb mouse was deficient in elastase, retaining only 10% of
      the activity of the normal littermates (hhHb). Skin myeloperoxidase activity was
      equally elevated in all the mice receiving UVB indicating a similar influx of
      inflammatory cells. The absolute breaking strength of the skin in both the hhBb
      and hhbb mice was not altered by UVB treatment over the 5 month exposure period.
      Elastin quantitated biochemically as desmosine, or visualized histologically, was
      increased following UVB exposure in the normal mice. In the elastase-deficient
      mice, however, the elastin fibres appeared to be unaffected by exposure to UVB
      radiation at this level. The results suggest that neutrophil elastase is an
      important mediator in the development of solar elastosis resulting from continued
      exposure to UVB.

PMID- 8575267
TI  - Molecular biophysics of elastin structure, function and pathology.
AB  - Owing to the presence of the recurring sequence XPGX' (where X and X' are
      hydrophobic residues), the molecular structure of the sequences between cross
      links in elastin is viewed primarily as a series of beta-turns which become
      helically ordered by hydrophobic folding into beta-spirals, which in turn
      assemble hydrophobically into twisted filaments. Both hydrophobic folding and
      assembly occur when the temperature is raised above Tt, the onset of an inverse
      temperature transition. Using poly[fv(VPGVG),fx(VPGXG)] (where fv and fx are mole
      fractions with fv + fx = 1 and X is now any of the naturally occurring amino acid
      residues), plots of fx versus Tt result in a new hydrophobicity scale based
      directly on the hydrophobic folding and assembly processes of interest. With the
      reference values chosen at fx = 1, the most hydrophobic residues of elastin, Tyr
      (Y) and Phe (F), have low values of Tt, -55 and -30 degrees C, respectively, and
      the most hydrophilic residues, Glu (E-), Asp (D-) and Lys (K+), have high values
      of 250, 170 and 120 degrees C, respectively. Raising the average value of Tt for
      a chain or chain segment from below to above physiological temperature drives
      hydrophobic unfolding and disassembly; lowering Tt does the reverse. This delta
      Tt mechanism has been used reversibly to interconvert many energy forms and is
      used here to explain initiating events of elastogenesis, pulmonary emphysema,
      solar elastosis and the paucity of elastic fibres in scar tissue. In general,
      oxidation and/or photolysis convert(s) hydrophobic residues into polar residues
      with the consequences of irreversibly raising Tt to above 37 degrees C,
      hydrophobic unfolding and disassembly (fibre swelling), and greater
      susceptibility to proteolysis.

PMID- 8575268
TI  - Structure of the elastin gene.
AB  - The isolation and characterization of cDNAs encompassing the full length of
      chicken, cow, rat and human elastin mRNA have led to the elucidation of the
      primary structure of the respective tropoelastins. Large segments of the sequence
      are conserved but there are also considerable variations which range in extent
      from relatively small alterations, such as conservative amino acid substitutions,
      to variation in the length of hydrophobic segments and largescale deletions and
      insertions. In general, smaller differences are found among mammalian
      tropoelastins and greater ones between chicken and mammalian tropoelastins.
      Although only a single elastin gene is found per haploid genome, the primary
      transcript is subject to considerable alternative splicing, resulting in multiple
      tropoelastin isoforms. Functionally distinct hydrophobic and cross-link domains
      of the protein are encoded in separate exons which alternate in the gene. The
      introns of the human gene are rich in Alu repetitive sequences, which may be the
      site of recombinational events, and there are also several dinucleotide repeats,
      which may exhibit polymorphism and, therefore, be effective genetic markers. The
      5' flanking region is G+C rich and contains potential binding sites for numerous
      modulating factors, but no TATA box or functional CAAT box. The basic promoter is
      contained within a 136 bp segment and transcription is initiated at multiple
      sites. These findings suggest that the regulation of elastin gene expression is
      complex and takes place at several levels.

PMID- 8575269
TI  - Regulation of elastin synthesis in pathological states.
AB  - Elastin is rapidly deposited during late gestation in resilient tissues such as
      the arteries, lungs and skin owing to increased concentration of its mRNA.
      Pathological states can arise from congenital insufficiency or disorganization of
      elastin (cutis laxa). Other elastin deficiencies may be due to excess elastolysis
      or gene dosage effects. In the former, high turnover rates can be assessed by
      measurements of elastin degradation products in urine. Excess elastin
      accumulation by skin fibroblasts is characteristic of genetic diseases such as
      Buschke-Ollendorff syndrome, Hutchinson-Gilford progeria and keloid. Elastin
      expression is modulated by peptide growth factors, steroid hormones and phorbol
      esters, among which transforming growth factor beta (TGF-beta) is an especially
      potent up-regulator, acting largely through stabilization of mRNA. Recent
      evidence indicates cutis laxa fibroblasts that express little or no elastin have
      normal transcriptional activity but abnormal rates of elastin mRNA degradation.
      This defect is substantially reversed by TGF-beta through mRNA stabilization.
      Current studies explore the hypothesis that stability determinants lie within the
      3' untranslated region of elastin mRNA. Post-transcriptional control of elastin
      expression appears to be a major regulatory mechanism.

PMID- 8575270
TI  - Densities of Ixodes ricinus ticks (Acari: Ixodidae) on moorland vegetation
      communities in the UK.
AB  - Unfed (questing) Ixodes ricinus ticks were collected by blanket dragging on a
      monthly basis from heather-dominated, Vaccinium-dominated and bracken-dominated
      vegetation communities from two different biogeographical regions of the UK (the
      Quantock Hills in Somerset, south west England and the North York Moors, north
      east England) throughout the spring and summer months of 1991 and 1992. Eighteen
      sites were monitored across the two regions and a total of 1920 blanket drags
      were carried out. Vaccinium sites showed high tick densities at all life stages,
      as did bracken sites. Significantly lower numbers of larval and nymphal ticks per
      drag were collected on heather sites than were collected on either Vaccinium
      (bilberry/whortleberry) or bracken sites, while similar numbers of adult ticks
      per drag were collected from each of the three vegetation communities. There was
      no significant difference between the mean numbers of any tick life stage
      collected on the Quantock Hills and those collected on the North York Moors on
      these vegetation communities or between the mean numbers of any tick life stage
      collected in 1991 and those collected in 1992 on these vegetation communities.

PMID- 8575271
TI  - Borrelia burgdorferi sensu lato in female cement plug of Ixodes persulcatus ticks
      (Acari, Ixodidae).
AB  - Borrelia burgdorferi sensu lato was detected in one out of five cement plugs of
      female Ixodes persulcatus ticks. The spirochetes were found by dark field
      microscopy as early as 18 h after attachment of the ticks to the skin of a white
      mouse. The relevance of this finding is discussed in relation to the epidemiology
      of Lyme borreliosis.

PMID- 8575272
TI  - A case of abnormal size in eggs and larvae of the Taiga tick, Ixodes persulcatus
      (Acari: Ixodidae).
AB  - Egg batches laid by females of Ixodes persulcatus (maintained under a photoperiod
      of L:D 20:4 before feeding) contained eggs of two sizes: numerous normal eggs of
      0.578 x 0.421 mm and some giant eggs of 0.776 x 0.515 mm. Giant eggs were 32-34%
      greater in length and 22-24% greater in width than normal eggs. Females
      maintained under a short-day photoperiod (L:D 12:12) laid only normal eggs (0.588
      x 0.417 mm). There were no differences between these eggs in viability and
      developmental time, but larvae hatched from giant eggs were larger (length of
      body 23-28% greater and of gnathosoma 12-15% greater) than larvae from normal
      eggs. This dimorphism of eggs and larvae was not sex determined, but may be a
      maternal photoperiodic effect.

PMID- 8575273
TI  - A comparison of Ixodes rubicundus (Acari: Ixodidae) infestations on Friesian and
      Bonsmara cattle in South Africa.
AB  - This study was conducted to compare the relative resistance of crossbred Bos
      indicus X B. taurus Bonsmara and B. taurus Friesian cattle to Ixodes rubicundus
      (Karoo paralysis tick) infestations. During periods of peak abundance of the
      ticks, Friesian oxen harboured almost twice or more than twice as many ticks as
      either Bonsmara oxen or cows. During periods of low tick abundance tick burdens
      on both cattle breeds were closely similar. It is envisaged that cattle can play
      an important role in an integrated control strategy against the Karoo paralysis
      tick.

PMID- 8575274
TI  - The efficiency of patch sampling for determination of relative tick burdens in
      comparison with total tick counts.
AB  - Quantitative data on host tick burdens are fundamental for the initiation of
      control strategies and effective management of wildlife populations, but the
      methods of live sampling employed for domestic animals are unsuitable for
      sampling wild animals. Despite advances in the use of destructive methods (the
      scrub and digestion techniques) to obtain measures of the total tick burden on
      wildlife, these methods are too involved for many field workers, who often need
      only measures of relative tick burden. Recently, patch sampling methods have been
      introduced whereby only certain predilection sites are sampled, the presumption
      being that the number of ticks collected gives an indication of the relative
      degree of infestation. We examined the validity of patch sampling as a measure of
      relative tick burden by comparing adult ticks collected from the ears, head,
      neck, foreleg and perianal region of impala (Aepyceros melampus) with total tick
      burdens of the same animals derived from the digestion technique. Adult ticks
      from patch sampling were positively and significantly correlated with total
      adults and total ticks (larvae, nymphs, and adults) on impala, with ticks patch
      sampled from the neck showing the highest correlation with the total tick burden.
      Comparison of relative tick loads from patch sampling with absolute tick loads
      from digestion for three classes of impala (females, bachelor males and
      territorial males) gave qualitatively similar results. We conclude that, when
      measures of relative tick load are sufficient and destructive sampling is not
      feasible, patch sampling can provide reliable information on relative tick
      burdens that are positively correlated with the total tick burden.

PMID- 8575275
TI  - Academic cytopathology: a specialty in transition.

PMID- 8575276
TI  - Unusual small bone metastases from epithelial malignancies: diagnosis by fine
      needle aspiration cytology with histologic confirmation.
AB  - Although epithelial malignancies can have bone metastases, involvement of small
      bones is exceedingly rare, representing either first manifestation of an occult
      carcinoma or late disseminated disease. Small bone metastases may mimic primary
      skeletal diseases leading to misdiagnosis and delayed treatment. We report three
      cases of metastatic epithelial malignancies diagnosed by computed tomography (CT)
      guided fine-needle aspiration (FNA) biopsy in two patients with lytic calcaneal
      lesions and a patellar lesion in a third patient; all with histologic
      confirmation. Case 1, a 63-year-old female, presented with heel pain. FNA and
      tissue biopsy of the calcaneus revealed a clear cell malignancy consistent with a
      renal primary. Follow-up abdominal CT scan revealed a renal lesion consistent
      with renal cell carcinoma. Case 2, a 37-yr-old male with squamous cell carcinoma
      of the esophagus, presented with foot pain. FNA and tissue biopsy of the
      calcaneous revealed metastatic squamous cell carcinoma. Case 3, a 52-yr-old male
      with a history of squamous cell carcinoma of floor of mouth, presented with knee
      pain and swelling. FNA and tissue biopsy of the patella revealed metastastic
      squamous cell carcinoma. To the best of our knowledge, this is the first complete
      FNA cytology report with histologic confirmation of unusual small bone metastases
      of the feet and patella from epithelial malignancies and shows the value of FNA
      cytology in establishing a correct diagnosis, and excluding primary skeletal
      diseases.

PMID- 8575277
TI  - Lobular carcinoma of the breast: cytological features supporting the diagnosis of
      lobular cancer.
AB  - Lobular carcinomas have a distinct natural history with a better response to
      endocrine therapy and a higher incidence of local recurrence and are more often
      bilateral. The cytological diagnosis of lobular carcinoma permits a
      discriminating therapeutic approach with pre-operative Tamoxifen, more generous
      resection margins, and assessment of the contralateral breast. The cytological
      features of lobular cancer however are not well defined and the low cell yield
      from such neoplasms can result in a high false negative rate. To determine
      whether we could improve the pre-operative diagnosis, we reviewed the cytological
      features of 112 lobular carcinomas. They had small uniform sized nuclei with
      irregular outlines and inconspicuous nucleoli. The degree of dissociation was
      similar to duct carcinomas and the incidence of inadequate aspirates was no
      higher. We found no features that confidently diagnosed lobular cancer or its sub
      types. However, using a combination of features, typing of lobular cancer on
      aspirated material is possible and should be attempted.

PMID- 8575278
TI  - Atypical endocervical glandular cells: accuracy of cytologic diagnosis.
AB  - Atypical cells thought to be of endocervical glandular origin often cause
      diagnostic uncertainty in cervicovaginal smears. For this reason consecutive
      cases of endocervical glandular atypia diagnosed in smears were correlated with
      subsequent biopsy diagnoses and then retrospectively reviewed. Smears were
      originally diagnosed as "mild glandular atypia, probably reactive" or "severe
      glandular atypia, suggestive of adenocarcinoma in situ" (AIS). Biopsy follow-up
      was obtained on 34 of 58 patients diagnosed with severe endocervical glandular
      atypia. Nine patients (26%) had AIS, three with concomitant high-grade squamous
      intraepithelial lesions (HSIL) and tow with invasive adenocarcinoma. Eighteen
      patients (53%) had HSIL only. Seven had benign changes. Of 152 patients diagnosed
      with mild glandular atypia, biopsy follow-up was obtained on 40. One patient had
      AIS; 14 (35%) had HSIL; one had low-grade SIL (LSIL); and 24 (60%) had benign
      changes. Blinded review of these smears yielded results similar to those in the
      biopsy follow-up, that is, the prediction of AIS on smears included most cases of
      AIS, some invasive adenocarcinomas, a significant number of HSIL, cases and a few
      benign lesions. A review diagnosis of "reactive glandular cells" proved to be
      HSIL in 31% of cases and AIS in one case. We conclude that patients with a
      diagnosis of severe glandular atypia in smears may prove to have AIS or invasive
      adenocarcinoma, but often have HSIL without concomitant AIS. In addition,
      although "reactive" glandular atypia in smears usually reflects a benign
      condition, a significant minority of such patients prove to have HSIL.

PMID- 8575279
TI  - Metastases to the thyroid gland: diagnosis by aspiration cytology.
AB  - The purpose of this study was to document the incidence, nature and source of
      neoplasms metastatic to the thyroid gland, which were diagnosed by fine needle
      aspiration (FNA) cytology. In the seven year period from 1986 to 1992, 21 cases
      were identified with metastatic malignancies in FNA specimens from the thyroid.
      This represented 7.5% of neoplastic thyroid lesions aspirated in this unit. All
      patients presented clinically with thyromegaly or discrete nodules. Only five
      patients were known to have malignancies of other sites prior to FNA. The
      majority of metastatic nodules were bronchogenic in origin (nine). The
      gastrointestinal tract (five) and melanomas (two) were the next most frequent
      sources in the series. Single cases arose in the prostate, larynx, kidney (all
      carcinomas), and uterus (a leiomyosarcoma). One patient had a thyroid deposit of
      acute myeloblastic leukemia. This large study demonstrated that tumors of many
      histological types may involve the thyroid gland, and furthermore, may masquerade
      as primary thyroid malignancies. Recognition of an alien cell type not only
      prevents inappropriate thyroid surgery, but may also direct the search for the
      unsuspected or unknown primary. Metastases to the thyroid gland occur more
      frequently than is generally appreciated. FNA is the procedure of choice for
      evaluation of thyroid nodules in general, and thyroid metastases in particular.

PMID- 8575280
TI  - Cytology, flow cytometry, image analysis, and interphase cytogenetics by
      fluorescence in situ hybridization in the diagnosis of transitional cell
      carcinoma in bladder washes: a comparative study.
AB  - The diagnosis of transitional cell carcinoma (TCC) in bladder washes is a
      diagnostic challenge to cytology. This study assessed the role of flow cytometry
      (FCM), image analysis (IA), and interphase cytogenetics by fluorescence in situ
      hybridization (FISH) as adjuncts in the cytodiagnosis of TCC in bladder washes.
      Forty separate samples of bladder washes were prospectively evaluated by
      conventional cytology (CY), FCM, IA, and FISH, and the results were compared with
      the subsequent surgical biopsy specimens which revealed 26 TCC (3 GR I, 6 GR II,
      17 GR III) and 14 benign lesions. Using histology as the "gold standard" and
      following the previously published criteria for detection of TCC by CY, FCM, IA,
      and FISH, the concordance rates between histology and CY, FCM, IA, and FISH were
      75, 74, 89, and 83%, respectively. CY, FCM, IA, FISH, and histology were
      concordant in 54% of the cases. The sensitivity of CY, FCM, IA, and FISH were 61,
      72, 91, and 73%, respectively, while the specificity were 100, 80, 83, and 100%,
      respectively. The combined sensitivity of all the parameters was 96%.
      Interestingly, the false positive cases by FCM and IA showed cystitis. We
      conclude that IA has the highest sensitivity in detecting TCC in bladder washes
      followed by FISH, FCM, and CY, while CY and FISH have the highest specificity.
      This study indicates that FCM, IA, and FISH are useful adjuncts to cytology in
      the diagnosis of TCC in bladder washes. The finding of DNA-aneuploidy in cystitis
      warrants further investigation.

PMID- 8575281
TI  - Detached single cilia: another potential pseudomicrobe seen in bronchoalveolar
      lavage specimens.
AB  - High magnification examination of Romanovsky-stained bronchoalveolar lavage (BAL)
      material may be needed, if one is to confidently exclude small organisms such as
      toxoplasmosis, histoplasmosis, and the negative images of mycobacteria.
      Pseudomicrobes have been described, and detailed criteria must be carefully
      applied, if incorrect diagnoses are to be avoided. We recently noted numerous
      free-lying, uniform, eosinophilic, straight or slightly curved bacilliform
      structures in such a specimen. These were seen on Diff-Quik-stained material, but
      were extremely pale on Papanicolaou-stained slides. Comparison with the cilia of
      contaminating bronchial cells showed these pseudomicrobes to have similar length,
      diameter, and tinctorial properties. Electron microscopy of the sedimented cell
      pellet showed isolated, detached single cilia (DSC) far removed from any
      bronchial cells. Twenty BAL's from 13 males and seven females (median age = 48.5)
      undergoing infection surveillance were then retrospectively reviewed. DSC were
      present in 16 specimens (80%), but were rare in three of these. Although present
      in cases with prominent bronchial cell contamination (n = 6 cases), DSC were also
      encountered when ciliated cells were rare (n = 13), or absent (n = 1).
      Familiarity with these distinctive structures should make it unlikely that they
      will be mistaken for infectious organisms.

PMID- 8575282
TI  - Role of fine-needle biopsy in the diagnosis of hydatid cyst.
AB  - The cytopathologic findings in 17 patients with hydatid cyst are reported. All
      patients but one were referred for evaluation of a tumor mass. In 13 patients the
      aspirated material was diagnostic of hydatid cyst. In four patients only
      acellular laminated membranes were present in the aspirate and a presumptive
      cytopathologic diagnosis of hydatid cyst was made. Subsequent histologic studies
      confirmed the diagnosis of hydatidosis in all patients. No complications were
      encountered. Fine-needle biopsy appears a safe diagnostic approach in the
      evaluation of suspected hydatid disease. The presence of acellular laminated
      membranes confirm the diagnosis of hydatid cyst.

PMID- 8575283
TI  - Solid and cystic papillary neoplasm of the pancreas: a clinico-cytopathologic and
      immunocytochemical study of five new cases diagnosed by fine-needle aspiration
      cytology and a review of the literature.
AB  - We report here on five new cases of solid and cystic papillary neoplasm (SCPN) of
      the pancreas diagnosed by fine-needle aspiration cytology (FNAC). All cytologic
      samples were obtained by ultrasonography, and the smears were conventionally
      fixed and stained. Special histochemical and immunocytochemical stains were also
      performed in some samples. Cytology revealed in all but one case numerous
      pseudopapillary structures composed of fibrovascular stalks lined with one or
      more layers of bland-appearing, uniform tumor cells. The tumor cells had round-to
      oval euchromatic nuclei with frequently folded smooth contours and one or two
      small nucleoli. Their cytoplasm often contained eosinophilic, PAS-positive, and
      diastase-resistant inclusions. Foamy cells, psammoma bodies, blood, and cellular
      debris were found in the background. The criteria for the differential diagnosis
      versus other pancreatic lesions are discussed in some detail, as is the role of
      immunocytochemistry (ICC). In the literature, only 28 cases of cytologically
      investigated SCPN have been reported to the best of our knowledge. The most
      helpful criteria for the conclusive identification of SCPN by FNAC include the
      pseudopapillary arrangement with bland-appearing tumor cells, and, especially,
      the finding of acidophilic, PAS-positive, and diastase-resistant cytoplasmic
      granules.

PMID- 8575284
TI  - Fine-needle aspiration cytology of superficial angiomyxoma (myxoid perifollicular
      fibroma): report of a case.
AB  - A case of superficial angiomyxoma arising in the areola of a 49-yr-old woman is
      presented, including both fine-needle aspiration cytology (FNAC) and histological
      study. The aspirate yielded a rich myxoid background with isolated fusiform
      cells, showing oval, monomorphic nuclei with minimal atypia. Sometimes these
      cells were arranged in small fragments without any specific pattern. The absence
      of mitotic figures, atypia, or cutaneous and breast epithelium suggested a benign
      myxoid stromal neoplasm. The final diagnosis was established on the excised mass
      by histopathologic study. The report of this entity in FNAC and the differential
      diagnosis with other myxoid lesions are discussed, and the feasibility of its
      cytological diagnosis by FNAC, helped by appropriate clinical information.

PMID- 8575285
TI  - Fine-needle aspiration cytology of ductal adenoma: report of a case associated
      with a mucocele-like lesion.
AB  - Ductal adenoma (DA) is an uncommon breast lesion that can histologically and
      clinically mimic carcinoma. We performed a fine-needle aspiration (FNA) of a DA.
      Cytologically, the lesion had features overlapping with those of mucinous
      carcinoma (MC), mucocele-like lesion, lactating adenoma (LA), and in retrospect
      with intraductal papilloma (IP). The smears were highly cellular and contained
      numerous monolayered sheets of ductal cells with prominent punched-out, small
      vacuoles distending the cytoplasm. The nuclei were mostly round to oval and had
      bland chromatin. Occasionally cells with enlarged nuclei and conspicuous nucleoli
      were present. The background showed large mucin pools, scattered single cells
      with mild nuclear atypia, some with apocrine metaplasia, rare stripped nuclei,
      and a fibrovascular stromal component. Calcifications were also present. We
      compare our cytologic findings with those of the lesions considered in the
      differential diagnosis. Due to its rare incidence and unusual features. DA may
      represent a diagnostic pitfall on FNA. Increased awareness of its cytologic
      appearance may help prevent a misdiagnosis.

PMID- 8575286
TI  - Peritoneal implantation of meningeal melanosis via ventriculoperitoneal shunt: a
      case report and review of the literature.
AB  - Systemic spread of primary intracranial neoplasms is rare and may be due to
      ventriculoperitoneal shunt (VPS). The most common tumors to metastasize via VPS
      are germinoma of the pineal gland and medulloblastoma. We report a case of 16-yr
      old girl with central nervous system malignant melanosis who developed subsequent
      peritoneal implants via VPS. To the best of our knowledge, this patient
      represents the third reported case of meningeal melanosis or melanoma which
      metastasized to the peritoneal cavity via VPS. The VPS should be considered as
      possible mode of systemic spread in patients with primary cranial malignancy.

PMID- 8575287
TI  - Typing and grading breast carcinoma on fine-needle aspiration: is this clinically
      useful information?
AB  - The ability of fine-needle aspiration (FNA) to diagnose breast cancer is beyond
      question. The established role of cytopathology is to maintain a low benign to
      malignant biopsy ratio by reducing the number of benign lesions excised. Both
      typing and grading of breast cancers on FNA have received attention in the
      cytology literature but how this knowledge can influence management has not been
      fully explored. Recently we described a method for the cytological grading of
      breast cancer that compares well with the established Bloom and Richardson
      grades. In this paper we present our experience of 1,387 breast cancer FNAs
      reported by us with histological verification. We show that cytologically typing
      and grading breast cancers are valid exercises that can predict the true nature
      of the neoplasm. This information may assist in the clinical approach to the
      malignant breast.

PMID- 8575288
TI  - Cytospins--an alternative method for fine-needle aspiration cytology of the
      breast: a study of 148 cases.
AB  - The aim of this study was to evaluate the cytospin technique as an alternative
      method to prepare fine-needle aspiration (FNA) specimens of the breast. To do so,
      the cytology of 148 breast FNAs that had been prepared by the cytospin technique
      and that had histologic correlation, was reviewed. All the cases that were
      diagnosed as malignant by cytology were proved malignant after surgical excision,
      and there were no false-positive results. All but two cases diagnosed as benign
      by cytology proved to be benign on excision. The two false-negative cases were
      missed due to sampling error. The cytological features seen on cytospins were
      similar to those seen on conventional direct smears. The major advantage of this
      method is that no aspirate is unsatisfactory due to unskilled direct smear
      technique. This, along with its good correlation with histology, proves that the
      cytospin method is an effective alternative to conventional direct smears for
      breast FNA.

PMID- 8575289
TI  - Quality control-quality assurance in diagnostic cytopathology: what's the
      difference...?

PMID- 8575290
TI  - Fine-needle aspiration of pilomatrixoma.

PMID- 8575291
TI  - Steps for residency training in cytology.

PMID- 8575292
TI  - Trying to drain the "ASCUS" swamp.

PMID- 8575293
TI  - Longitudinal organization of the anterior neural plate and neural tube.
AB  - Over the last century, several morphological models of forebrain organization
      have been proposed that hypothesize alternative topological solutions for the
      relationships of the histogenic primordia. Central to all of these models are
      their definitions of the longitudinal axis and the longitudinal organization of
      the neural plate and neural tube. To understand the longitudinal organization of
      the anterior brain, we have sought to identify molecular properties that are
      continuous along the entire longitudinal axis of the embryonic CNS. In this
      essay, we describe studies of the expression of several genes in the mouse
      between 7.5 (presomite stage) and 10.5 days post coitum (dpc) that provide
      evidence for the trajectory of the anterior-posterior axis and the longitudinal
      organization of the anterior CNS. Specifically, we report that the expression of
      noggin, sonic hedgehog and Nkx-2.2 define longitudinal columns of cells that are
      present along the entire CNS axis. Within the forebrain, the expression of these
      genes, as well as that of Nkx-2.1 and BF-1, are in distinct longitudinal regions
      in the neural plate and tube. We demonstrate that the earliest longitudinal axon
      pathways of the forebrain are spatially correlated with the longitudinal domain
      defined by Nkx-2.2. Finally, expression of the former genes, and Otx-1 and Emx-2,
      suggests that the cephalic neural plate is organized into molecularly distinct
      domains delimited by longitudinal and transverse borders; these results provide a
      foundation for defining the mechanisms that pattern the neural plate.

PMID- 8575294
TI  - A role for En-2 and other murine homologues of Drosophila segment polarity genes
      in regulating positional information in the developing cerebellum.
AB  - To gain insight into the molecular genetic basis of cerebellar patterning, the
      expression patterns of many vertebrate homologues of Drosophila segment polarity
      genes were examined during normal and abnormal cerebellar development, including
      members of the En, Wnt, Pax, Gli and Dvl gene families. Five of these genes were
      found to show transient, spatially restricted patterns of expression. Strikingly,
      expression of En-2, En-1, Wnt-7B and Pax-2 defined eleven similar sagittal
      domains at 17.5 dpc, reminiscent of the transient sagittal domains of expression
      of Purkinje cell markers which have been implicated in cerebellar afferent
      patterning. Postnatally, transient anterior/posterior differences in expression
      were observed for En-2, En-1, Gli and Wnt-7B dividing the cerebellum into
      anterior and posterior regions. The expression patterns of these genes were
      altered in cerebella of En-2 homozygous mutant mice, which show a cerebellar
      foliation patterning defect. Strikingly, four of the Wnt-7B expression domains
      that are adjacent to the En-2 domains are lost in En-2 mutant embryonic
      cerebella. These studies provide the first evidence of a potential network of
      regulatory genes that establish spatial cues in the developing cerebellum by
      dividing it into a grid of positional information required for patterning
      foliation and afferents. Taken together with previous gene expression studies,
      our data suggests that eleven sagittal domains and at least two
      anterior/posterior compartments are the basic elements of spatial information in
      the cerebellum.

PMID- 8575295
TI  - The role of yan in mediating the choice between cell division and
      differentiation.
AB  - An allele of the yan locus was isolated as an enhancer of the Ellipse mutation of
      the Drosophila epidermal growth factor receptor (Egfr) gene. This yan allele is
      an embryonic lethal and also fails to complement the lethality of anterior open
      (aop) mutations. Phenotypic and complementation analysis revealed that aop is
      allelic to yan and genetically the lethal alleles act as null mutations for the
      yan gene. Analysis of the lethal alleles in the embryo and in mitotic clones
      showed that loss of yan function causes cells to overproliferate in the dorsal
      neuroectoderm of the embryo and in the developing eye disc. Our studies suggest
      that the role of yan is defined by the developmental context of the cells in
      which it functions. An important role of this gene is in allowing a cell to
      choose between cell division and differentiation. The relationship of the Egfr
      and Notch pathways to this developmental role of yan is discussed.

PMID- 8575296
TI  - Expression of a truncated FGF receptor results in defective lens development in
      transgenic mice.
AB  - Members of the fibroblast growth factor (FGF) family are thought to initiate
      biological responses through the activation of cell surface receptors which must
      dimerize to transmit an intracellular signal. Mammalian lens epithelial cells
      respond to exogenous extracellular FGF, either in tissue culture or in transgenic
      mice, by initiating fiber cell differentiation. The role of FGF signalling in
      normal lens development was evaluated by lens-specific synthesis of a kinase
      deficient FGF receptor type I (FGFR1) in transgenic mice. This truncated FGF
      receptor is thought to act as a dominant negative protein by heterodimerization
      with endogenous FGF receptors. The presence of transgenic mRNA in the lens was
      confirmed by in situ hybridization and by polymerase chain reaction amplification
      of reverse transcribed lens RNA (RT-PCR). The presence of transgenic protein was
      determined by Western blotting with antibodies to an extracellular domain of
      FGFR1. Three of four transgenic families expressing the truncated FGF receptor
      exhibited lens defects ranging from cataracts to severe microphthalmia. While the
      microphthalmic lenses displayed a normal pattern of differentiation-specific
      crystallin expression, the lens epithelial cells were reduced in number and the
      lens fiber cells displayed characteristics consistent with the induction of
      apoptosis. Our results support the view that FGF receptor signalling plays an
      essential role in normal lens biology.

PMID- 8575297
TI  - Differential regulation of AP-1 and novel TRE-specific DNA-binding complexes
      during differentiation of oligodendrocyte-type-2-astrocyte (O-2A) progenitor
      cells.
AB  - AP-1 is an ubiquitous transcription factor which is composed of the Jun and Fos
      proto-oncogene proteins and is thought to play a role in both cell proliferation
      and differentiation. We have used an immortal, bipotential oligodendrocyte-type-2
      astrocyte progenitor cell line (O-2A/c-myc) which can differentiate into
      oligodendrocytes or type-2 astrocytes in vitro, to investigate whether AP-1 DNA
      binding activity fluctuates during glial cell differentiation. Unexpectedly, DNA
      mobility shift assays using a TRE-containing oligonucleotide derived from the
      promoter of the glial-specific gene, glial fibrillary acidic protein (GFAP/AP-1),
      revealed that O-2A/c-myc progenitor cells were devoid of conventional AP-1 DNA
      binding complexes. O-2A/c-myc cells did however contain several novel GFAP/AP-1
      specific DNA-binding complexes, which we have termed APprog. APprog complexes
      recognise the TRE consensus motif present in the GFAP/AP-1 oligonucleotide
      together with adjacent 3' sequences but do not contain c-Jun or any other known
      Jun-related proteins. When O-2A/c-myc cells underwent terminal differentiation
      APprog complexes were lost and conventional AP-1 DNA-binding activity became
      evident, particularly in astrocytes. These changes appear to be closely linked to
      the differentiation process since they did not occur in a derivative of the O
      2A/c-myc cell line that contains an activated v-ras oncogene and which fails to
      differentiate under appropriate culture conditions. The inverse regulation of
      conventional AP-1 and APprog complexes within the O-2A lineage suggests that
      these factors may play a role in the regulation of glial cell differentiation or
      glial cell-specific gene expression.

PMID- 8575298
TI  - Specific modulation of ectodermal cell fates in Xenopus embryos by glycogen
      synthase kinase.
AB  - Shaggy is a downstream component of the wingless and Notch signaling pathways
      which operate during Drosophila development. To address the role of glycogen
      synthase kinase 3 beta (GSK3 beta), a mammalian homologue of Shaggy, in
      vertebrate embryogenesis, it was overexpressed in Xenopus embryos. Microinjection
      of rat GSK3 beta mRNA into animal ventral blastomeres of 8-cell-stage embryos
      triggered development of ectopic cement glands with an adjacent anterior neural
      tissue as evidenced by in situ hybridization with Xotx2, a fore/midbrain marker,
      and NCAM, a pan-neural marker. In contrast, animal dorsal injection of the same
      dose of GSK3 beta mRNA caused eye deficiencies, whereas vegetal injections had no
      pronounced effects on normal development. Using several mutated forms of rat GSK3
      beta, we demonstrate that the observed phenotypes are dose-dependent and tightly
      correlate with GSK3 beta enzymatic activity. Lineage tracing experiments showed
      that the effects of GSK3 beta are cell autonomous and that ectopic cement glands
      and eye deficiencies arose directly from cells containing GSK3 beta mRNA.
      Molecular marker analysis of ectodermal explants overexpressing GSK3 beta has
      revealed activation of Xotx2 and of cement gland marker XAG-1, but expression of
      NCAM and XIF-3 was not detected. Phenotypic effects of mRNA encoding a Xenopus
      homologue of GSK3 beta were identical to those of rat GSK3 beta mRNA. We
      hypothesize that GSK3 beta mediates the initial steps of neural tissue
      specification and modulates anteroposterior ectodermal patterning via activation
      of Otx2 transcription. Our observations implicate GSK3 beta in signaling pathways
      operating during neural tissue development and during specification of anterior
      ectodermal cell fates.

PMID- 8575299
TI  - Evolution of neuroblast identity: seven-up and prospero expression reveal
      homologous and divergent neuroblast fates in Drosophila and Schistocerca.
AB  - In the Drosophila CNS, early neuroblast formation and fate are controlled by the
      pair-rule class of segmentation genes. The distantly related Schistocerca
      (grasshopper) embryo has a similar arrangement of neuroblasts, despite lack of
      known pair-rule gene function. Does divergent pair-rule gene function lead to
      different neuroblast identities, or can different patterning mechanisms produce
      homologous neuroblasts? We use four molecular markers to compare Drosophila and
      Schistocerca neuroblast identity: seven-up, prospero, engrailed, and fushi
      tarazu/Dax. In both insects some early-forming neuroblasts share key features of
      neuroblast identity (position, time of formation, and temporally accurate gene
      expression); thus, different patterning mechanisms can generate similar
      neuroblast fates. In contrast, several later-forming neuroblasts show species
      specific differences in position and/or gene expression; these neuroblast
      identities seem to have diverged, suggesting that evolution of the insect central
      nervous system can occur through changes in embryonic neuroblast identity.

PMID- 8575300
TI  - Mouse embryos lacking RXR alpha are resistant to retinoic-acid-induced limb
      defects.
AB  - Embryonic exposure to the vitamin A metabolite retinoic acid (RA) causes
      malformations in numerous developing tissues, including the limbs, which serves
      as a model system of retinoic acid action. RA treatment of wild-type mouse
      embryos results in digit truncations and long bone reductions. These effects are
      mediated by products of the retinoic acid and retinoid X receptor genes (RARs and
      RXRs), members of the nuclear receptor family of ligand-dependent transcription
      factors. Mouse embryos homozygous for a mutation in the RXR alpha gene appear
      normal in limb development, although such embryos are phenotypically affected in
      other tissues. We now describe resistance to limb malformations normally induced
      by teratogenic RA exposure in the RXR alpha-/- background. RA treatments that
      cause limb defects in 100% of wild-type embryos fail to elicit malformations in
      RXR alpha homozygotes, implicating RXR alpha as a component in the teratogenic
      process in the limbs. Heterozygous embryos are intermediate in sensitivity to RA,
      suggesting the importance of RXR alpha gene dosage in limb teratogenesis.
      Expression of the RA-inducible gene RAR beta 2 was equivalent between wild-type
      and homozygous embryos after RA treatment. RA treatment also did not distinguish
      between wild-type and RXR alpha -/- embryos in the spatial expression of sonic
      hedgehog (Shh) and hoxd-12, two other genes implicated in limb development.
      However, the quantitative level of hoxd-12 expression was elevated in RXR alpha 
      /- embryos. These observations indicate that transcriptional processes which are
      inappropriately regulated in the mouse limb by exogenous RA require RXR alpha for
      their execution, and that specific teratogenic processes, as well as specific
      normal developmental processes under vitamin A control, occur through individual
      members of the RXR and RAR families.

PMID- 8575301
TI  - Expression of truncated Sek-1 receptor tyrosine kinase disrupts the segmental
      restriction of gene expression in the Xenopus and zebrafish hindbrain.
AB  - During development of the vertebrate hindbrain regulatory gene expression is
      confined to precise segmental domains. Studies of cell lineage and gene
      expression suggest that establishment of these domains may involve a dynamic
      regulation of cell identity and restriction of cell movement between segments. We
      have taken a dominant negative approach to interfere with the function of Sek-1,
      a member of the Eph-related receptor tyrosine kinase family expressed in
      rhombomeres r3 and r5. In Xenopus and zebrafish embryos expressing truncated Sek
      1, lacking kinase sequences, expression of r3/r5 markers occurs in adjacent even
      numbered rhombomeres, in domains contiguous with r3 or r5. This disruption is
      rescued by full-length Sek-1, indicating a requirement for the kinase domain in
      the segmental restriction of gene expression. These data suggest that Sek-1,
      perhaps with other Eph-related receptors, is required for interactions that
      regulate the segmental identity or movement of cells.

PMID- 8575302
TI  - The gene virilizer is required for female-specific splicing controlled by Sxl,
      the master gene for sexual development in Drosophila.
AB  - The gene virilizer (vir) is needed for dosage compensation and sex determination
      in females and for an unknown vital function in both sexes. In genetic mosaics,
      XX somatic cells mutant for vir differentiate male structures. One allele, vir2f,
      is lethal for XX, but not for XY animals. This female-specific lethality can be
      rescued by constitutive expression of Sxl or by mutations in msl (male-specific
      lethal) genes. Rescued animals develop as strongly masculinized intersexes or
      pseudomales. They have male-specifically spliced mRNA of tra, and when rescued by
      msl, also of Sxl. Our data indicate that vir is a positive regulator of female
      specific splicing of Sxl and of tra pre-mRNA.

PMID- 8575303
TI  - Evolutionary conservation of a cell fate specification gene: the Hydra achaete
      scute homolog has proneural activity in Drosophila.
AB  - Members of the Achaete-scute family of basic helix-loop-helix transcription
      factors are involved in cell fate specification in vertebrates and invertebrates.
      We have isolated and characterized a cnidarian achaete-scute homolog, CnASH, from
      Hydra vulgaris, a representative of an evolutionarily ancient branch of
      metazoans. There is a single achaete-scute gene in Hydra, and the bHLH domain of
      the predicted gene product shares a high degree of amino acid sequence similarity
      with those of vertebrate and Drosophila Achaete-scute proteins. In Hydra, CnASH
      is expressed in a subset of the interstitial cells as well as differentiation
      intermediates of the nematocyte pathways. In vitro translated CnASH protein can
      form heterodimers with the Drosophila bHLH protein Daughterless, and these dimers
      bind to consensus Achaete-scute DNA binding sites in a sequence-specific manner.
      Ectopic expression of CnASH in wild-type late third instar Drosophila larvae and
      early pupae leads to the formation of ectopic sensory organs, mimicking the
      effect of ectopic expression of the endogenous achaete-scute genes. Expression of
      CnASH in flies that are achaete and scute double mutants gives partial rescue of
      the mutant phenotype, comparable to the degree of rescue obtained by ectopic
      expression of the Drosophila genes. These results indicate that the achaete-scute
      type of bHLH genes for cell fate specification, as well as their mode of action,
      arose early and have been conserved during metazoan evolution.

PMID- 8575304
TI  - The porcupine gene is required for wingless autoregulation in Drosophila.
AB  - The Drosophila segment polarity gene wingless (wg) is required in the regulation
      of engrailed (en) expression and the determination of cell fates in neighboring
      cells. This paracrine wg activity also regulates transcription of wg itself,
      through a positive feedback loop including en activity. In addition, wg has a
      second, more direct autoregulatory requirement that is distinct from the en
      dependent feedback loop. Four gene products, encoded by armadillo (arm),
      dishevelled (dsh), porcupine (porc) and zeste-white 3 (zw3), have been previously
      implicated as components of wg paracrine signaling. Here we have used three
      different assays to assess the requirements of these genes in the more direct wg
      autoregulatory pathway. While the activities of dsh, zw3 and arm appear to be
      specific to the paracrine feedback pathway, the more direct autoregulatory
      pathway requires porc.

PMID- 8575305
TI  - Six3, a murine homologue of the sine oculis gene, demarcates the most anterior
      border of the developing neural plate and is expressed during eye development.
AB  - The Drosophila sine oculis homeobox-containing gene is known to play an essential
      role in controlling the initial events of pattern formation in the eye disc and
      is also required for the development of other parts of the fly visual system
      including the optic lobes. In this paper, we report the isolation of a sequence
      related gene referred to as Six3. Based on its amino acid sequence, this gene can
      be included in the new Six/sine oculis subclass of homeobox genes. Early on, Six3
      expression is restricted to the anterior neural plate including areas that later
      will give rise to ectodermal and neural derivatives. Later, once the longitudinal
      axis of the brain bends, Six3 mRNA is also found in structures derived from the
      anterior neural plate: ectoderm of nasal cavity, olfactory placode and Rathke's
      pouch, and also the ventral forebrain including the region of the optic recess,
      hypothalamus and optic vesicles. Based on this expression pattern, we conclude
      that Six3 is one of the most anterior homeobox gene reported to date. The high
      sequence similarity of Six3 with the Drosophila sine oculis, and its expression
      during eye development, suggests that this gene is the likely murine homologue.
      This finding supports the idea that mammals and insects share control genes such
      as eyeless/Pax6 (Halder, G., Callaerts, P. and Gehring, W. J. (1995) Science 267,
      1788-1792), and also possibly other members of the regulatory cascade required
      for eye morphogenesis. In Small eye (Pax6) mouse mutants Six3 expression is not
      affected. Finally, based on the chromosomal localization and the expression
      pattern of the mouse Six3 gene, the human Six3 cognate could be a good candidate
      to be at least one of the genes affected in patients with holoprosencephaly type
      2 due to an interstitial deletion of 2p21-p22. This region shares a homology with
      the distal region of mouse chromosome 17 where Six3 has been mapped.

PMID- 8575306
TI  - Pax-2 controls multiple steps of urogenital development.
AB  - Urogenital system development in mammals requires the coordinated differentiation
      of two distinct tissues, the ductal epithelium and the nephrogenic mesenchyme,
      both derived from the intermediate mesoderm of the early embryo. The former give
      rise to the genital tracts, ureters and kidney collecting duct system, whereas
      mesenchymal components undergo epithelial transformation to form nephrons in both
      the mesonephric (embryonic) and metanephric (definitive) kidney. Pax-2 is a
      transcriptional regulator of the paired-box family and is widely expressed during
      the development of both ductal and mesenchymal components of the urogenital
      system. We report here that Pax-2 homozygous mutant newborn mice lack kidneys,
      ureters and genital tracts. We attribute these defects to dysgenesis of both
      ductal and mesenchymal components of the developing urogenital system. The
      Wolffian and Mullerian ducts, precursors of male and female genital tracts,
      respectively, develop only partially and degenerate during embryogenesis. The
      ureters, inducers of the metanephros are absent and therefore kidney development
      does not take place. Mesenchyme of the nephrogenic cord fails to undergo
      epithelial transformation and is not able to form tubules in the mesonephros. In
      addition, we show that the expression of specific markers for each of these
      components is de-regulated in Pax-2 mutants. These data show that Pax-2 is
      required for multiple steps during the differentiation of intermediate mesoderm.
      In addition, Pax-2 mouse mutants provide an animal model for human hereditary
      kidney diseases.

PMID- 8575307
TI  - Differential effects of combined trk receptor mutations on dorsal root ganglion
      and inner ear sensory neurons.
AB  - We have generated double mutant mice deficient in pairs of two different Trk
      receptors and have analysed the effects on survival and differentiation of dorsal
      root ganglion (DRG), inner ear cochlear and vestibular sensory neurons. In most
      combinations of mutant trk alleles, the defects observed in double compared to
      single mutant mice were additive. However, double homozygous trkA-/-;trkB-/- DRG
      and trkB-/-;trkC-/- vestibular neurons showed the same degree of survival as
      single trkA-/- and trkB-/- mice, respectively, suggesting that those neurons
      required both Trk signaling pathways for survival. In situ hybridisation analysis
      of DRG neurons of double mutant mice revealed differential expression of
      excitatory neuropeptides. Whereas calcitonin-gene-related peptide expression
      correlated with the trkA phenotype, substance P expression was detected in all
      combinations of double mutant mice. In the inner ear, TrkB- and TrkC-dependent
      neurons were shown to at least partially depend on each other for survival, most
      likely indirectly due to abnormal development of their common targets. This
      effect was not observed in DRGs, where neurons depending on different Trk
      receptors generally innervate different targets.

PMID- 8575308
TI  - Lineage restriction of the myogenic conversion factor myf-5 in the brain.
AB  - myf-5 is one of four transcription factors belonging to the MyoD family that play
      key roles in skeletal muscle determination and differentiation. We have shown
      earlier by gene targeting nlacZ into the murine myf-5 locus that myf-5 expression
      in the developing mouse embryo is closely associated with the restriction of
      precursor muscle cells to the myogenic lineage. We now identify unexpected
      expression of this myogenic factor in subdomains of the brain. myf-5 expression
      begins to be detected at embryonic day 8 (E8) in the mesencephalon and coincides
      with the appearance of the first differentiated neurons; expression in the
      secondary prosencephalon initiates at E10 and is confined to the ventral domain
      of prosomere p4, later becoming restricted to the posterior hypothalamus. This
      expression is observed throughout embryogenesis. No other member of the MyoD
      family is detected in these regions, consistent with the lack of myogenic
      conversion. Furthermore, embryonic stem cells expressing the myf-5/nlacZ allele
      yield both skeletal muscle and neuronal cells when differentiated in vitro. These
      observations raise questions about the role of myf-5 in neurogenesis as well as
      myogenesis, and introduce a new lineage marker for the developing brain.

PMID- 8575309
TI  - Role of the morphogenetic furrow in establishing polarity in the Drosophila eye.
AB  - The Drosophila retina is a crystalline array of 800 ommatidia whose organization
      and assembly suggest polarization of the retinal epithelium along anteroposterior
      and dorsoventral axes. The retina develops by a stepwise process following the
      posterior-to-anterior progression of the morphogenetic furrow across the eye
      disc. Ectopic expression of hedgehog or local removal of patched function
      generates ectopic furrows that can progress in any direction across the disc
      leaving in their wake differentiating fields of ectopic ommatidia. We have
      studied the effect of these ectopic furrows on the polarity of ommatidial
      assembly and rotation. We find that the anteroposterior asymmetry of ommatidial
      assembly parallels the progression of ectopic furrows, regardless of their
      direction. In addition, ommatidia developing behind ectopic furrows rotate
      coordinately, forming equators in various regions of the disc. Interestingly, the
      expression of a marker normally restricted to the equator is induced in ectopic
      ommatidial fields. Ectopic equators are stable as they persist to adulthood,
      where they can coexist with the normal equator. Our results suggest that ectopic
      furrows can impart polarity to the disc epithelium, regarding the direction of
      both assembly and rotation of ommatidia. We propose that these processes are
      polarized as a consequence of furrow propagation, while more global determinants
      of dorsoventral and anteroposterior polarity may act less directly by determining
      the site of furrow initiation.

PMID- 8575311
TI  - Regulative response of the cranial neural tube after neural fold ablation:
      spatiotemporal nature of neural crest regeneration and up-regulation of Slug.
AB  - After unilateral ablation of the avian cranial neural folds, the remaining
      neuroepithelial cells are able to replace the missing neural crest population
      (Scherson et al., 1993). Here, we characterize the cellular and molecular nature
      of this regulative response by defining: (1) the time and location of neural
      crest cell production by the neuroepithelium; (2) rostrocaudal axial differences
      in the regulative response; and (3) the onset of expression of Slug, a
      transcription factor present in premigratory and migrating neural crest cells.
      Using DiI and HNK-1 antibody labeling techniques, we find that neural crest
      regeneration occurs only after apposition of the remaining neuroepithelium with
      the epidermis, suggesting that the developmental mechanism underlying
      regeneration of the neural crest may recapitulate initial generation of the
      neural crest. The regulative response occurs maximally at the 3-5 somite stage,
      and slowly declines thereafter. Surprisingly, there are profound regional
      differences in the regenerative ability. Whereas a robust regulation occurs in
      the caudal midbrain/hindbrain, the caudal forebrain/rostral midbrain regenerates
      neural crest to a much lesser extent. After neural fold removal in the hindbrain,
      regenerated neural crest cells migrate in a segmental pattern analogous to that
      seen in unablated embryos; a decrease in regulative response appears to occur
      with increasing depth of the ablation. Up-regulation of Slug appears to be an
      early response after ablation, with Slug transcripts detectable proximal to the
      ablated region 5-8 hours after surgery and prior to emergence of neural crest
      cells. Both bilateral and unilateral ablations yield substantial numbers of
      neural crest cells, though the former recover less rapidly and have greater
      deficits in neural crest-derived structures than the latter. These experiments
      demonstrate that the regulative ability of the cranial neuroepithelium to form
      neural crest depends on the time, location and extent of neural fold ablation.

PMID- 8575310
TI  - Dishevelled is a component of the frizzled signaling pathway in Drosophila.
AB  - The tissue polarity genes in Drosophila are required to coordinate cell polarity
      within the plane of the epidermis. Evidence to date suggests that these genes may
      encode components of a novel signal transduction pathway. Three of the genes,
      frizzled (fz), dishevelled (dsh), and prickle (pk) share a similar tissue
      polarity phenotype, suggesting that they function together in a single process.
      dsh is also known to function as a mediator of wingless (wg) signaling in a
      variety of developmental patterning processes in the fly. In this study, we make
      use of a fz transgene and a hypomorphic fz allele as genetic tools in an attempt
      to order these genes in a genetic hierarchy. Our results argue that dsh encodes a
      dosage sensitive component required for fz function and that it likely acts
      downstream of fz in the generation of tissue polarity. Our findings suggest that
      dsh may have a general role in signal transduction, perhaps as a component of a
      receptor complex.

PMID- 8575313
TI  - Spatial regulation of Drosophila snake protease activity in the generation of
      dorsal-ventral polarity.
AB  - Positional information along the dorsal-ventral axis of the Drosophila embryo is
      acquired through a signal transduction pathway which employs a extracellular
      protease cascade. The sequential activation of serine protease zymogens results
      in the ventrally localized production of a ligand in the perivitelline space of
      the embryo. Snake is one of several serine proteases which function in generating
      the ventralizing signal. Here, we investigate the biochemical properties of Snake
      in vivo and in vitro using recombinant forms of the protease. Wild-type Snake
      zymogen completely rescues embryos from snake null females when microinjected
      into the perivitelline space. Biochemical evidence for a covalently associated
      two-chain form of the activated protease is presented. The contribution of the
      activation peptide region to zymogen activation was addressed using site-directed
      mutagenesis. The phenotypic rescue properties of an autoactivated form of Snake
      reveal that the covalently associated proenzyme polypeptide chain suppresses a
      dominant effect associated with the activated catalytic chain alone. Recombinant
      active catalytic chain was produced and found to be short lived as a recombinant
      protein. These results suggest a model in which the proenzyme polypeptide both
      stabilizes and targets the Snake catalytic chain to a ventrally localized
      activation complex within the perivitelline space.

PMID- 8575312
TI  - Motoneuron fate specification revealed by patterned LIM homeobox gene expression
      in embryonic zebrafish.
AB  - In zebrafish, individual primary motoneurons can be uniquely identified by their
      characteristic cell body positions and axonal projection patterns. The fate of
      individual primary motoneurons remains plastic until just prior to axogenesis
      when they become committed to particular identities. We find that distinct
      primary motoneurons express particular combinations of LIM homeobox genes.
      Expression precedes axogenesis as well as commitment, suggesting that LIM
      homeobox genes may contribute to the specification of motoneuronal fates. By
      transplanting them to new spinal cord positions, we demonstrate that primary
      motoneurons can initiate a new program of LIM homeobox gene expression, as well
      as the morphological features appropriate for the new position. We conclude that
      the patterned distribution of different primary motoneuronal types within the
      zebrafish spinal cord follows the patterned expression of LIM homeobox genes, and
      that this reflects a highly resolved system of positional information controlling
      gene transcription.

PMID- 8575314
TI  - Cooperative interactions between extracellular matrix, integrins and parathyroid
      hormone-related peptide regulate parietal endoderm differentiation in mouse
      embryos.
AB  - The outgrowth of parietal endoderm (PE) cells from precursor endodermal cells is
      one of the first differentiation events that occur in mouse embryos. We have
      analyzed the molecular determinants of this process by placing isolated inner
      cell masses (ICMs) on defined extracellular matrix substrata in microdrop
      cultures. Differentiation and outgrowth of PE required a fibronectin substratum.
      Laminin supported the adhesion and outgrowth of visceral endoderm (VE) and
      actively suppressed the differentiation of PE in mixtures of fibronectin and
      laminin. Collagen type IV, gelatin, vitronectin or entactin supported little or
      no endodermal outgrowth. Trophectoderm (TE) cells have been implied to be
      important in PE induction in vivo. We found that recombination of ICMs in culture
      with TE cells, or with medium conditioned by TE cells, greatly increased the
      differentiation of PE. TE cells stimulated PE outgrowth on substrata other than
      fibronectin. One cytokine secreted by trophoblast and endodermal cells,
      parathyroid hormone-related peptide (PTHrP), was critical for outgrowth on any
      substratum. A function-perturbing antibody to PTHrP reduced the number of PE
      cells, whereas the addition of PTHrP increased that number. Furthermore, addition
      of PTHrP changed the substratum requirements for outgrowth, making laminin,
      vitronectin and low concentrations of fibronectin permissive for PE outgrowth.
      Immunostaining with anti-integrin antibodies showed that fully differentiated PE
      cells outgrowing on fibronectin expressed alpha 5, alpha 6 and alpha v beta 3
      integrins. However, analysis of outgrowths in the presence of function-perturbing
      antibodies to alpha 5, alpha 6 and alpha v beta 3 integrins showed that these
      integrins directed PE outgrowth only on fibronectin, laminin and vitronectin
      substrata, respectively. We have shown that there is a cooperative interplay of
      extracellular matrix, integrins and PTHrP that modulates PE outgrowth.

PMID- 8575315
TI  - headcase, an imaginal specific gene required for adult morphogenesis in
      Drosophila melanogaster.
AB  - The majority of adult organs of a holometabolic insect like Drosophila
      melanogaster are derived from specific imaginal cells. These cells differ from
      their larval equivalents in many important cellular characteristics, ranging from
      the nature of the cell cycle to the timing and pattern of cellular
      differentiation. Here we describe the cellular, molecular and genetic
      characterization of a gene, headcase (hdc), which is required for imaginal cell
      development. hdc is the first gene to be described which is specifically
      expressed in all imaginal cells; this has allowed us to identify many imaginal
      primordia in the embryo and larval development. The Hdc protein is an extremely
      basic (pI 9.6) cytoplasmic protein with no obvious sequence similarities or
      conserved motifs. Interestingly, the spatial-temporal pattern of hdc expression
      prefigures imaginal cell re-entry into the mitotic cell cycle and persists until
      the final cell divisions. hdc null alleles have been isolated and found to cause
      pupal lethality, with dead pharate adults exhibiting defects in the
      differentiation of many adult tissues, most notably in head development. Ectopic
      expression of hdc, provided by a hdc-minigene, rescues the pupal lethality.
      Imaginal disc morphology in null mutants appears normal, therefore loss of hdc
      expression does not affect imaginal cell growth, but instead interferes with the
      ability of the imaginal primordia to differentiate properly during pupal
      development, suggesting that hdc may be involved in hormonal responsiveness
      during metamorphosis.

PMID- 8575316
TI  - patched overexpression alters wing disc size and pattern: transcriptional and
      post-transcriptional effects on hedgehog targets.
AB  - The membrane protein, Patched, plays a critical role in patterning embryonic and
      imaginal tissues in Drosophila. patched constitutively inactivates the
      transcription of target genes such as wingless, decapentaplegic, and patched
      itself. The secreted protein, Hedgehog, induces transcription of target genes by
      opposing the Patched signaling pathway. Using the Gal4 UAS system we have
      overexpressed patched in wing imaginal discs and found that high Patched levels,
      expressed in either normal or ectopic patterns, result in loss of wing vein
      patterning in both compartments centering at the anterior/posterior border. In
      addition, patched inhibits the formation of the mechanosensory neurons, the
      campaniform sensilla, in the wing blade. The patched wing vein phenotype is
      modulated by mutations in hedgehog and cubitus interruptus (ci). Patched
      overexpression inhibits transcription of patched and decapentaplegic and post
      transcriptionally decreases the amount of Ci protein at the anterior/posterior
      boundary. In hedgehogMrt wing discs, which express ectopic hedgehog, Ci levels
      are correspondingly elevated, suggesting that hedgehog relieves patched
      repression of Ci accumulation. Protein kinase A also regulates Ci; protein kinase
      A mutant clones in the anterior compartment have increased levels of Ci protein.
      Thus patched influences wing disc patterning by decreasing Ci protein levels and
      inactivating hedgehog target genes in the anterior compartment.

PMID- 8575317
TI  - The expression of the Athb-8 homeobox gene is restricted to provascular cells in
      Arabidopsis thaliana.
AB  - We have characterized an Arabidopsis homeobox gene coding for a putative DNA
      binding protein that represents an early marker for vascular development. The
      full-length cDNA encodes a protein of 833 amino acids that we have designated
      Athb-8; it contains the conserved DNA binding domain that characterizes the HD
      Zip family of transcription factors. RNA analysis showed that the Athb-8 gene is
      expressed during the vegetative and the reproductive phases of plant growth. A
      higher steady-state level of the Athb-8 mRNA was found in flowering stem and
      root. In situ mRNA analysis of Arabidopsis plants demonstrated that Athb-8
      expression is restricted to the procambial cells of embryo and developing organs.
      Moreover, Athb-8-GUS expression was found in single parenchyma cells which are
      differentiating into tracheary elements in wounded tobacco transgenic plants.
      Finally, we showed that the auxin, indole-3-acetic acid, which is involved in
      vascular development and differentiation, modulates the expression of the gene.
      Taken together, these results suggest that Athb-8 might be a regulator of
      vascular development in Arabidopsis thaliana.

PMID- 8575318
TI  - Anterior-posterior subdivision and the diversification of the mesoderm in
      Drosophila.
AB  - We have used a novel cell marker, in which the twist promoter directs the
      synthesis of the cell surface protein CD2 (twi-CD2) to examine the development of
      the mesoderm in the Drosophila embryo after gastrulation and to locate the
      progenitor cell populations for different mesodermal derivatives. We find that
      the early mesoderm in each segment is divided into a more anterior region with
      relatively low levels of twist and twi-CD2 expression and a more posterior region
      where twist and twi-CD2 expression are high. This subdivision coincides with
      regional assignments of cells to form different progenitors: dorsal anterior
      cells invaginate to form an internal layer from which the visceral mesoderm is
      derived. Ventral anterior cells form progenitors of mesodermal glial cells.
      Dorsal posterior cells form heart. Ventral and dorsal posterior cells form
      somatic muscles. We conclude that the metamerically repeated anterior-posterior
      subdivision of the mesoderm is an essential element in laying out the pattern of
      mesodermal progenitor cells and in distinguishing between an internal cell layer
      which will give rise to the progenitors of visceral muscles and an external layer
      which will generate the somatic muscles and the heart.

PMID- 8575319
TI  - Temporal and spatial regulation of H19 imprinting in normal and uniparental mouse
      embryos.
AB  - The mouse H19 gene is imprinted so that the paternal copy is both methylated and
      repressed during fetal development. However, the CpG-rich promoter region
      encompassing the transcription start is not methylated in sperm; this region must
      therefore become methylated postzygotically. We first examined the timing of DNA
      methylation of this region and the corresponding expression of H19. Both parental
      copies are initially undermethylated in blastocysts and the paternal copy then
      becomes fully methylated in the embryo around implantation; this methylation is
      more protracted in the extraembryonic lineages, especially in the trophoblast. By
      contrast to the lineage-dependent methylation, we observed exclusive expression
      of the maternal copy in preimplantation embryos and in all the lineages of early
      postimplantation embryos although variability may exist in cultured embryos. This
      indicates that methylation of the CpG-rich promoter is not a prerequisite for the
      paternal repression. We then examined whether methylation and expression occurs
      appropriately in the absence of a maternal or a paternal genome. Both H19 copies
      in androgenetic embryos are fully methylated while they are unmethylated in
      parthenogenetic embryos. This correlates with the lack of expression in
      androgenetic embryos but expression in parthenogenetic embryos. However, the
      androgenetic trophoblast was exceptional as it shows reduced methylation and
      expresses H19. These results suggest that promoter methylation is not the primary
      inactivation mechanism but is a stabilizing factor. Differential methylation in
      the more upstream region, which is established in the gametes, is a likely
      candidate for the gametic signal and may directly control H19 activity.

PMID- 8575320
TI  - Induction of avian cardiac myogenesis by anterior endoderm.
AB  - An experimental system was devised to study the mechanisms by which cells become
      committed to the cardiac myocyte lineage during avian development. Chick tissues
      from outside the fate map of the heart (in the posterior primitive streak (PPS)
      of a Hamburger & Hamilton stage 4 embryo) were combined with potential inducing
      tissues from quail embryos and cultured in vitro. Species-specific RT-PCR was
      employed to detect the appearance of the cardiac muscle markers chick Nkx-2.5
      (cNkx-2.5), cardiac troponin C and ventricular myosin heavy chain in the chick
      responder tissues. Using this procedure, we found that stage 4-5 anterior lateral
      (AL) endoderm and anterior central (AC) mesendoderm, but not AL mesoderm or
      posterior lateral mesendoderm, induced cells of the PPS to differentiate as
      cardiac myocytes. Induction of cardiogenesis was accompanied by a marked decrease
      in the expression of rho-globin, implying that PPS cells were being induced by
      anterior endoderm to become cardiac myocytes instead of blood-forming tissue.
      These results suggest that anterior endoderm contains signaling molecules that
      can induce cardiac myocyte specification of early primitive streak cells. One of
      the cardiac muscle markers induced by anterior endoderm, cNkx-2.5, is here
      described for the first time. cNkx-2.5 is a chick homeobox-containing gene that
      shares extensive sequence similarity with the Drosophila gene tinman, which is
      required for Drosophila heart formation. The mesodermal component of cNkx-2.5
      expression from stage 5 onward, as determined by in situ hybridization, is
      strikingly in accord with the fate map of the avian heart. By the time the
      myocardium and endocardium form distinct layers, cNkx-2.5 is found only in the
      myocardium. cNkx-2.5 thus appears to be the earliest described marker of avian
      mesoderm fated to give rise to cardiac muscle.

PMID- 8575321
TI  - Serrate signals through Notch to establish a Wingless-dependent organizer at the
      dorsal/ventral compartment boundary of the Drosophila wing.
AB  - Growth and patterning of the Drosophila wing is controlled by organizing centers
      located at the anterior-posterior and dorsal-ventral compartment boundaries.
      Interaction between cells in adjacent compartments establish the organizer. We
      report here that Serrate and Notch mediate the interaction between dorsal and
      ventral cells to direct localized expression of Wingless at the D/V boundary.
      Serrate serves as a spatially localized ligand which directs Wg expression
      through activation of Notch. Ligand independent activation of Notch is sufficient
      to direct Wg expression, which in turn mediates the organizing activity of the
      D/V boundary.

PMID- 8575322
TI  - Conserved and divergent expression aspects of the Drosophila segmentation gene
      hunchback in the short germ band embryo of the flour beetle Tribolium.
AB  - The segmentation gene hunchback (hb) plays a central role in determining the
      anterior-posterior pattern in the Drosophila embryo. We have cloned the homologue
      of hb from the flour beetle Tribolium and show that, on the basis of its
      expression pattern, most of its functions seem to be conserved between these two
      species. Like Drosophila, Tribolium has a maternal hb expression that appears to
      be under translational control by a factor at the posterior pole of the embryo.
      The maternal expression is followed by a zygotic expression in the region of the
      developing head and thoracic segments. During germ band extension, a posterior
      expression domain appears that is likely to be homologous to the posterior
      blastoderm expression of hb in Drosophila. These observations suggest that hb may
      have the same functions in early Drosophila and Tribolium development, despite
      the different types of embryogenesis in these two species (long versus short germ
      development). One differing aspect of hb expression in Tribolium concerns a
      structure that is not present in Drosophila, namely the serosa. An hb expression
      domain at the anterior pole precisely demarcates the border between the
      extraembryonic serosa and the embryonic field in the Tribolium embryo at an early
      stage, and hb protein remains expressed in the serosa cells until the end of
      embryogenesis.

PMID- 8575323
TI  - The limb deformity mutation disrupts the SHH/FGF-4 feedback loop and regulation
      of 5' HoxD genes during limb pattern formation.
AB  - Mutations in the murine limb deformity (ld) gene disrupt differentiation of the
      Apical Ectodermal Ridge (AER) and patterning of distal limb structures. However,
      initial outgrowth of the limb bud is not affected, suggesting that early and late
      functions of the AER are uncoupled. Similarly, activation of the 5' members of
      the HoxD gene cluster (Hoxd-11 to Hoxd-13) is not affected in ld mutant posterior
      limb bud mesenchyme, but the subsequent anteriorization of 5' HoxD domains is
      delayed by about 12 hours and is associated with reduced levels of polarising
      activity. These results indicate that the ld gene products act upstream of 5'
      HoxD genes during patterning of the autopod. Expression of the signalling
      molecule Sonic hedgehog (Shh) in the posterior limb bud mesenchyme is initiated
      normally, but ceases prematurely indicating a defect in maintenance of Shh by the
      ld mutant AER. Furthermore, no Fgf-4 transcripts are detected in the ld mutant
      AER, whereas Fgf-8 transcripts remain expressed. However, Shh expression can be
      rescued by heterospecific grafting of ld mutant posterior mesenchyme under a wild
      type chicken AER. These studies show that the AER defect in ld homozygous limb
      buds causes disruption of the FGF-4/SHH feedback loop and support the proposed
      essential role for FGF-4 in maintaining Shh expression during limb pattern
      formation.

PMID- 8575324
TI  - Ommatidial polarity in the Drosophila eye is determined by the direction of
      furrow progression and local interactions.
AB  - The adult eye of Drosophila is a highly ordered structure. It is composed of
      about 800 ommatidia, each displaying precise polarity. The ommatidia are arranged
      about an axis of mirror image symmetry, the equator, which lies along the
      dorsoventral midline of the eye. We use hedgehog pathway mutants to induce
      ectopic morphogenetic furrows and use these as a tool to investigate the
      establishment of ommatidial polarity. Our results show that ommatidial clusters
      are self-organising units whose polarity in one axis is determined by the
      direction of furrow progression, and which can independently define the position
      of an equator without reference to the global coordinates of the eye disc.

PMID- 8575325
TI  - Cell-autonomous shift from axial to paraxial mesodermal development in zebrafish
      floating head mutants.
AB  - Zebrafish floating head mutant embryos lack notochord and develop somitic muscle
      in its place. This may result from incorrect specification of the notochord
      domain at gastrulation, or from respecification of notochord progenitors to form
      muscle. In genetic mosaics, floating head acts cell autonomously. Transplanted
      wild-type cells differentiate into notochord in mutant hosts; however, cells from
      floating head mutant donors produce muscle rather than notochord in wild-type
      hosts. Consistent with respecification, markers of axial mesoderm are initially
      expressed in floating head mutant gastrulas, but expression does not persist.
      Axial cells also inappropriately express markers of paraxial mesoderm. Thus,
      single cells in the mutant midline transiently co-express genes that are normally
      specific to either axial or paraxial mesoderm. Since floating head mutants
      produce some floor plate in the ventral neural tube, midline mesoderm may also
      retain early signaling capabilities. Our results suggest that wild-type floating
      head provides an essential step in maintaining, rather than initiating,
      development of notochord-forming axial mesoderm.

PMID- 8575326
TI  - Periaxin expression in myelinating Schwann cells: modulation by axon-glial
      interactions and polarized localization during development.
AB  - Periaxin is a newly described protein that is expressed exclusively by
      myelinating Schwann cells. In developing nerves, periaxin is first detected as
      Schwann cells ensheathe axons, prior to the appearance of the proteins that
      characterize the myelin sheath. Periaxin is initially concentrated in the
      adaxonal membrane (apposing the axon) but, during development, as myelin sheaths
      mature, periaxin becomes predominately localized at the abaxonal Schwann cell
      membrane (apposing the basal lamina). In permanently axotomized adult nerves,
      periaxin is lost from the abaxonal and adaxonal membranes, becomes associated
      with degenerating myelin sheaths and is phagocytosed by macrophages. In crushed
      nerves, in which axons regenerate and are remyelinated, periaxin is first
      detected in the adoxonal membrane as Schwann cells ensheathe regenerating axons,
      but again prior to the appearance of other myelin proteins. Periaxin mRNA and
      protein levels change in parallel with those of other myelin-related genes after
      permanent axotomy and crush. These data demonstrate that periaxin is expressed by
      myelinating Schwann cells in a dynamic, developmentally regulated manner. The
      shift in localization of periaxin in the Schwann cell after completion of the
      spiralization phase of myelination suggests that periaxin participates in
      membrane-protein interactions that are required to stabilize the mature myelin
      sheath.

PMID- 8575327
TI  - Interchangeability of Caenorhabditis elegans DSL proteins and intrinsic
      signalling activity of their extracellular domains in vivo.
AB  - Ligands of the Delta/Serrate/lag-2 (DSL) family and their receptors, members of
      the lin-12/Notch family, mediate cell-cell interactions that specify cell fate in
      invertebrates and vertebrates. In C. elegans, two DSL genes, lag-2 and apx-1,
      influence different cell fate decisions during development. Here we show that APX
      1 can fully substitute for LAG-2 when expressed under the control of lag-2
      regulatory sequences. In addition, we demonstrate that truncated forms lacking
      the transmembrane and intracellular domains of both LAG-2 and APX-1 can also
      substitute for endogenous lag-2 activity. Moreover, we provide evidence that
      these truncated forms are secreted and able to activate LIN-12 and GLP-1
      ectopically. Finally, we show that expression of a secreted DSL domain alone may
      enhance endogenous LAG-2 signalling. Our data suggest ways that activated forms
      of DSL ligands in other systems may be created.

PMID- 8575328
TI  - Conservation of Brachyury (T) genes in amphioxus and vertebrates: developmental
      and evolutionary implications.
AB  - Homologues of the murine Brachyury (T) gene have been cloned from several
      vertebrates, and are implicated in mesoderm formation and in differentiation of
      the notochord. In contrast, the roles of the ascidian Brachyury gene may be
      restricted to presumptive notochord. To understand the evolution of Brachyury
      genes and their developmental roles, we have searched for homologues in
      amphioxus, representing the third chordate subphylum and the probable closest
      relative of the vertebrates. We report the isolation of two amphioxus cDNA clones
      with clear homology to Brachyury genes, and demonstrate that these derive from
      separate loci resultant from a recent gene duplication. This finding represents
      an exception to the emerging consensus of an archetypal prevertebrate genome in
      amphioxus. The spatial and temporal distribution of Brachyury transcripts during
      amphioxus development is remarkably similar to vertebrate Brachyury, in
      presumptive mesoderm, posterior mesoderm and the notochord. Gene expression
      extends throughout the anteroposterior axis of the notochord, despite the most
      rostral regions being a more recent specialization; it also persists into larval
      stages, despite differentiation into contractile tissue. We propose that roles of
      Brachyury in notochord differentiation are more ancient than roles in mesoderm
      formation, and that the latter are shared by cephalochordates and all
      vertebrates.

PMID- 8575329
TI  - Anti-dorsalizing morphogenetic protein is a novel TGF-beta homolog expressed in
      the Spemann organizer.
AB  - We have identified a novel growth factor in Xenopus, which is most closely
      related to human Bone Morphogenetic Protein-3. Its expression peaks during
      gastrulation, most prominently in the Spemann organizer, and persists in the
      posterior neural floor plate and prechordal plate during neurulation. Injection
      of the corresponding mRNA into dorsal blastomeres results in dose-dependent
      suppression of dorsal and anterior structures, even in the presence of lithium
      chloride. Overexpression of the gene downregulates the dorsalizing factors
      noggin, goosecoid and follistatin, as well as the dorsal markers NCAM, muscle
      actin and MyoD; conversely, ventral markers are induced. We therefore designate
      this gene product Anti-Dorsalizing Morphogenetic Protein (ADMP). Though
      development of dorsoanterior structures is suppressed when exogenous ADMP is
      injected, the gene is induced by lithium chloride treatment or activin, both of
      which are known to produce the opposite effect. Thus, the expression of ADMP
      resembles that of several dorsalizing signals, but its product exerts dorsal
      suppressing activity. This suggests that ADMP may moderate organizer-associated
      dorsalizing influences. These findings are also consistent with the recently
      advanced proposal of dorsally expressed inhibitory activin-like signals.

PMID- 8575330
TI  - Segmental patterning of heart precursors in Drosophila.
AB  - The mesoderm of Drosophila embryos is segmented; for instance there are
      segmentally arranged clusters of cells (some of which are heart precursors) that
      express even-skipped. Expression of even-skipped depends on Wingless, a secreted
      molecule. In principle, Wingless could act directly in the mesoderm or it could
      induce the pattern after crossing from ectoderm to mesoderm. Using mosaic
      embryos, we show that Wingless produced in the mesoderm is sufficient for even
      skipped expression. This proves that induction is not essential. However,
      induction can occur: when patches of wingless mutant mesoderm are overlaid by
      wild-type ectoderm, they do express even-skipped. We therefore believe that
      Wingless from both the ectoderm and mesoderm may contribute to patterning the
      mesoderm. Using the UAS/Gal4 system, we made embryos in which the Wingless
      protein is uniformly expressed. This is sufficient to rescue the repeated
      clusters of even-skipped expressing cells, although they are enlarged. We
      conclude that the mesoderm is segmented in some way not dependent on the
      distribution of Wingless, suggesting a more permissive and less instructive role
      for the protein in this instance.

PMID- 8575331
TI  - Overexpression of a membrane protein, neuropilin, in chimeric mice causes
      anomalies in the cardiovascular system, nervous system and limbs.
AB  - Neuropilin is a type 1 membrane protein, which is highly conserved among Xenopus
      frog, chicken and mouse. The extracellular part of the neuropilin protein is
      composed of three unique domains, each of which is thought to be involved in
      molecular and/or cellular interactions. In mice, neuropilin is expressed in the
      cardiovascular system, nervous system and limbs at particular developmental
      stages. To clarify the roles of neuropilin in morphogenesis in vivo, we generated
      mouse embryonic stem (ES) cell clones that constitutively expressed exogenous
      neuropilin, then produced chimeras using these ES cell clones. The chimeras
      overexpressed neuropilin and were embryonic lethal. The chimeric embryos
      exhibited several morphological abnormalities; excess capillaries and blood
      vessels, dilation of blood vessels, malformed hearts, ectopic sprouting and
      defasciculation of nerve fibers, and extra digits. All of these abnormalities
      occurred in the organs in which neuropilin is expressed in normal development.
      The variety of abnormalities occurring in these chimeric embryos suggested
      diverse functions of neuropilin in embryonic morphogenesis, which may be ascribed
      to multiple interaction domains identified in the molecule. Correct
      spatiotemporal expression of neuropilin seems to be essential for normal
      development of the cardiovascular system, nervous system and limbs.

PMID- 8575332
TI  - Drosophila short gastrulation induces an ectopic axis in Xenopus: evidence for
      conserved mechanisms of dorsal-ventral patterning.
AB  - The Spemann organizer has long been recognized as a major source of patterning
      signals during the gastrula stage of amphibian embryogenesis. More recent
      evidence has suggested that the ventral side of the embryo also plays an
      important role in dorsal-ventral patterning during gastrulation through the
      action of signaling factors such as BMP-4. Bmp-4 is closely related to the
      Drosophila decapentaplegic (dpp) gene, and like Bmp-4, dpp is excluded from the
      neurogenic region. Recently we showed that Bmp-4 functions in an analogous role
      to that of dpp in Drosophila, suggesting that the mechanism of dorsal-ventral
      patterning in Xenopus and Drosophila embryos may be conserved. To further test
      this hypothesis, RNA of the Drosophila short gastrulation (sog) gene was injected
      into Xenopus embryos, since sog has been shown genetically to be an antagonist of
      dpp function. Overexpression of sog RNA in Xenopus dorsalizes the embryo by
      expanding neurogenic and dorsal paraxial tissue. When ectopically expressed on
      the ventral side of the embryo, sog induces a partial secondary axis. In
      addition, sog partially rescues embryos ventralized by ultraviolet irradiation.
      Since sog induces many similar changes in gene expression to that caused by
      truncated BMP receptors, we suggest that sog functions in part by opposing BMP-4
      signaling. The recent identification of a possible Xenopus sog homolog, chordin,
      in conjunction with these results supports the hypothesis that dorsal-ventral
      patterning mechanisms are conserved between these two species.

PMID- 8575333
TI  - Gene expression, polarising activity and skeletal patterning in reaggregated hind
      limb mesenchyme.
AB  - The developing chick limb has two major signalling centres; the apical ectodermal
      ridge maintains expression of several important genes and outgrowth of the limb,
      and the polarising region specifies the pattern of skeletal elements along the
      anteroposterior axis. We have used reaggregated leg grafts (mesenchyme
      dissociated into single cells, placed in an ectodermal jacket and grafted to a
      host) to study patterning in a system where the developmental axes are severely
      disrupted. Reaggregates from different regions of leg mesenchyme developed
      correspondingly different digits, giving a system in which skeletal phenotype
      could be compared with the expression of genes thought to be important in
      patterning. We found that posterior third and whole leg reaggregates gave rise to
      different digits, yet expressed the same combination of HoxD, Bmp-2 and shh genes
      throughout their development. Anterior thirds initially only express the 3' end
      of the HoxD cluster but activate the more 5' members of the cluster sequentially
      over a period of 48 hours, a period during which Bmp-2 is activated but no shh or
      Fgf-4 expression could be detected. Our results suggest that there are two
      independent mechanisms for activating the HoxD complex, one polarising region
      dependent and one independent, and that shh expression may not be necessary to
      maintain outgrowth and patterning once a ridge has been established.

PMID- 8575334
TI  - Regulation of Hoxc-8 during mouse embryonic development: identification and
      characterization of critical elements involved in early neural tube expression.
AB  - We have characterized cis-acting elements that direct the early phase of Hoxc-8
      expression using reporter gene analysis in transgenic mice. By deletion we show
      that a 135 bp DNA fragment, located approximately 3 kb upstream of the coding
      region of Hoxc-8, is capable of directing posterior neural tube expression. This
      early neural tube (ENT) enhancer consists of four separate elements, designated
      A, B, C and D, whose nucleotide sequences are similar to binding sites of known
      transcription factors. Nucleotide substitutions suggest that element A is an
      essential component of the ENT enhancer. However element A by itself is incapable
      of directing neural tube expression. This element requires interactions at any
      two of the other three elements, B, C or D. Thus, the components of the ENT
      enhancer direct neural tube expression in an interdependent manner. We propose
      that Hoxc-8 is activated in the neural tube by combinatorial interactions among
      several proteins acting within a small region. Our transgenic analyses provide a
      means to identify transcription factors that regulate Hoxc-8 expression during
      embryogenesis.

PMID- 8575335
TI  - Caudalization of neural fate by tissue recombination and bFGF.
AB  - In order to study anteroposterior neural patterning in Xenopus embryos, we have
      developed a novel assay using explants and tissue recombinants of early neural
      plate. We show, by using region-specific neural markers and lineage tracing, that
      posterior axial tissue induces midbrain and hindbrain fates from prospective
      forebrain. The growth factor bFGF mimics the effect of the posterior dorsal
      explant in that it (i) induces forebrain to express hindbrain markers, (ii)
      induces prospective hindbrain explants to make spinal cord, but not forebrain and
      midbrain, and (iii) induces posterior neural fate in ectodermal explants
      neuralized by the dominant negative activin receptor and follistatin without
      mesoderm induction. The competence of forebrain explants to respond to both
      posterior axial explants and bFGF is lost by neural groove stages. These findings
      demonstrate that posterior neural fate can be derived from anterior neural
      tissue, and identify a novel activity for the growth factor bFGF in neural
      patterning. Our observations suggest that full anteroposterior neural patterning
      may be achieved by caudalization of prospective anterior neural fate in the
      vertebrate embryo.

PMID- 8575336
TI  - Rhodopsin plays an essential structural role in Drosophila photoreceptor
      development.
AB  - Null mutations of the Drosophila Rh1 rhodopsin gene, ninaE, result in
      developmental defects in the photosensitive membranes, the rhabdomeres, of
      compound eye photoreceptors R1-R6. In normal flies, Rh1 expression begins at
      about 78% of pupal life. At approximately 90% of pupal life, a specialized
      catacomb-like membrane architecture develops at the base of normal rhabdomeres.
      In ninaE null mutants, these catacombs do not form and developing rhabdomere
      membrane involutes into the cell as curtains of apposed plasma membrane. A
      filamentous cytoskeletal complex that includes F-actin and the unconventional
      myosin, NINAC, decorates the cytoplasmic surface of these curtains.

PMID- 8575337
TI  - Early even-skipped stripes act as morphogenetic gradients at the single cell
      level to establish engrailed expression.
AB  - even-skipped (eve) has been proposed to set up parasegment borders at the
      anterior edge of each of its seven stripes by providing a sharp expression
      boundary, where engrailed is activated on one side and wingless on the other. By
      expressing bell-shaped early eve stripes without the sharp boundary provided by
      narrow, late stripes, we find that the early gradient is sufficient for
      generating stable parasegment borders. Based on several lines of evidence, we
      propose that the anterior portion of each early stripe has morphogenic activity,
      repressing different target genes at different concentrations. These distinct
      repression thresholds serve to both limit and subdivide a narrow zone of paired
      expression. Within this zone, single cell rows express either engrailed, where
      runt and sloppy-paired are repressed, or wingless, where they are not. While the
      early eve gradient is sufficient to establish parasegmental borders without
      refined, late expression, late eve expression has a role in augmenting this
      boundary to provide for strong, continuous stripes or engrailed expression. In
      addition, we show that the early eve gradient is sufficient, at its posterior
      edge, for subdividing the ftz domain into engrailed expressing and non-expressing
      cells.

PMID- 8575338
TI  - FGF suppresses apoptosis and induces differentiation of fibre cells in the mouse
      lens.
AB  - To determine whether fibroblast growth factor (FGF) has a role in lens
      development, we have generated transgenic mice expressing a dominant-negative
      form of the murine FGF receptor-1 (FGFRDN) in the lens. Using the fibre cell
      specific alpha A-crystallin promoter to express the FGFRDN, we have asked whether
      FGF is required for fibre cell differentiation. The transgenic mice display
      diminished differentiation of fibre cells as indicated by their reduced
      elongation. In addition, transgenic lenses have an unusual refractile anomaly
      that morphological and biochemical data show results from the apoptosis of fibre
      cells in the central region of the lens. These results show that lens fibre cells
      are dependent on FGF for their survival and differentiation, and demonstrate that
      growth factor deprivation in vivo can lead to apoptosis.

PMID- 8575339
TI  - Metabolic trafficking between neurons and astrocytes: the glutamate/glutamine
      cycle revisited.
AB  - Use of 13C-labeled precursors for the neuroactive amino acids glutamate and GABA
      as well as [U-13C]glutamate and glutamine combined with NMR spectroscopy has
      allowed detailed studies to be performed on cultured neurons and astrocytes
      yielding new information about synthesis and metabolism of these amino acids at
      the cellular level. Thus, it has become clear that astrocytes metabolize
      glutamate extensively through the tricarboxylic acid (TCA) cycle in a rather
      complex manner enabling the cells to generate lactate from malate. It has been
      shown that astrocytes can supply neurons not only with glutamine but also with
      TCA cycle constituents, lactate and alanine. Hence, an extended version of the
      glutamate/glutamine cycle is presented. Moreover, it has been demonstrated that
      citrate synthesized in astrocytes and released into the extracellular space can
      modify neuronal activity by regulating the Zn2+ concentration and thereby
      modulate N-methyl-D-aspartate receptor-mediated depolarization.

PMID- 8575340
TI  - Postnatal development of the complexes of the electron transport chain in
      synaptic mitochondria from rat brain.
AB  - The postnatal development of the complexes of the electron transport chain in
      mitochondria isolated from rat brain synaptosomes was investigated. Synaptosomal
      brain mitochondria were isolated from rats aged 10-60 days, and the activities of
      mitochondrial complex I, complex II-III, complex IV and complex V were measured.
      There was a significant increase in the activity of II-III from day 10 to day 15
      and complex IV from day 10 to day 21, thereafter the activities of complexes I
      III and IV did not change significantly. The activity of complex I did not change
      significantly during the period 10-60 days post partum. In synaptic mitochondria,
      complex V activity was higher than in non-synaptic mitochondria, whereas the
      activity of complex I was lower than in non-synaptic mitochondria. These data
      show that the complexes of the respiratory chain within synaptic mitochondria
      have activities different from those of non-synaptic mitochondria and may have
      major implications for the relative susceptibility of mitochondria in different
      brain cell types to neurotoxins such as MPP+, hypoxic/ischaemic damage and
      oxidative stress.

PMID- 8575341
TI  - Dendritic alterations of cortical pyramidal neurons in postnatally lead-exposed
      kittens: a Golgi-Cox study.
AB  - Cortical pyramidal cell development was studied in postnatally lead-exposed
      kittens by light microscopic and Golgi staining methods. The most evident finding
      was an elevation of spine density on the distal apical dendritic branches of lead
      treated kittens. Also, the branching pattern of the apical dendrites in lead
      treated animals was different from control, but there was no overall change in
      total branch number of the dendritic arbor. Pyramidal cell height and cortical
      thickness were unaffected. No evidence of vascular damage or other pathologies
      were found in hematoxylin and eosin-stained sections. The results are discussed
      with reference to dendritic spine development and function and to other reports
      of hyperspiny dendrites. Evidence of hyperspiny dendrites in the present study
      indicates this represents a useful protocol for investigating dendritic spine
      development and differentiation.

PMID- 8575342
TI  - Communicating hydrocephalus in dogs with congenital ciliary dysfunction.
AB  - Magnetic resonance imaging (MRI) and radionuclide ventriculography were performed
      in 5 dogs with congenital ciliary dysfunction (CDD) and 3 normal dogs.
      Ventricular and brain dimensions and volumes, and CSF flow rates were measured or
      calculated from the MR images and radionuclide clearance. All CCD dogs had
      hydrocephalus based on previously published criteria of a percent vertical brain
      dimension (PVBD) greater than 14%. The PVBD was significantly larger (p = 0.001)
      in the dogs with CCD (mean +/- SD) 33.00 +/- 5.42% than in normal dogs (11.07 +/-
      0.61%. The ventricular volume was significantly larger (p = 0.021) in CCD dogs
      10,841 +/- 4,127 mm3 compared to the volume measured in normal dogs 3,069 +/-
      1,167 mm3. The CSF flow rate was not significantly different p = 0.876) between
      CCD dogs (253.00 +/- 147.25 mm3/h) and normal dogs (267.667 +/- 47.61 mm3/h).
      This suggests that the ventricular dilation in CCD dogs is not due to impedance
      of CSF flow from the ventricular system by dysfunctional ependymal cilia.

PMID- 8575343
TI  - Maturation of kitten ventral medullary surface activity during pressor
      challenges.
AB  - We used large-array optical recording procedures to examine maturation of
      regional neural activity within the ventral medullary surface (VMS) of
      anesthetized kittens during pharmacologically induced blood pressure elevation.
      Under sodium pentobarbital anesthesia, the VMS was exposed in 10, 20 and 30- to
      45-day-old kittens and in adult cats. Arterial pressure, costal diaphragmatic
      EMG, and ECG were continuously monitored. An imaging camera, composed of a charge
      coupled device and a coherent bundle of optic fibers, was positioned over the
      VMS. Light at 660 nm illuminated the neural tissue, and was collected by the
      probe. Resulting light-scatter images were acquired at 2-second intervals during
      a baseline period, and following intravenous administration of phenylephrine at
      10, 20 and 40 micrograms/kg. Sixty to seventy-five images within each epoch were
      averaged, and subtracted from baseline. Regional differences within the image
      were determined by ANOVA procedures (alpha = 0.05). Phenylephrine elicited dose
      dependent elevations of blood pressure accompanied by decreased diaphragmatic EMG
      activity which were less profound in younger animals. With maturation,
      responsiveness of respiratory patterning to the pressor response increased. In
      contrast to adult cats, 10-day kittens increased VMS neural activity in a dose
      dependent fashion with pressor stimulation. A progressive transition to adult
      response patterns was observed with increasing postnatal age, and was established
      in over half of the kittens by 30-45 days. We conclude that phenylephrine-induced
      baroreceptor stimulation elicits divergent VMS activity responses in developing
      and mature animals. Such a developmental pattern may reflect immature function of
      central and/or peripheral baroreflexes.

PMID- 8575344
TI  - Distribution of somatostatin receptor subtype 1 mRNA in the developing cerebral
      hemispheres of the rat.
AB  - Somatostatin (SST) is one of the major peptide transmitters in the mammalian
      central nervous system and also seems to exert specific functions during brain
      development. In contrast to ligand binding experiments, by which two
      pharmacologically different binding sites were characterized, molecular cloning
      techniques have led to the identification of at least five different receptor
      subtypes (SSTR1-5), which according to RNA blot analyses seem to be
      differentially distributed and regulated in the developing brain. In order to
      provide more precise data on the distribution of SSTR1 during ontogenesis, we
      have performed an in situ hybridization analysis, using a 35S-labelled RNA probe,
      in the developing rat cortex between embryonic day (E)12 and adulthood. Within
      the cortical plate, expression of SSTR1 gene was first detected in parallel with
      the establishment of the deep laminae V/VI at E16, thereby following the
      characteristic morphogenetic gradients of cortical plate construction. Thus, with
      the subsequent addition of cells along the radial dimension, e.g. the deposition
      of the supragranular neurons beyond E18, the hybridization signal spreads as an
      uniform homogenous band through the entire cortical plate, whereby silver grains
      reach their peak density around birth. Similar developmental gradients were
      observed along the lateromedial and frontooccipital dimension, whereby SSTR1
      transcripts were detected near the frontal pole and the lateral cortical areas
      roughly 2 days before they appeared in the occipital and medial cortical anlage,
      respectively. From the initially homogenous distribution, two distinct SSTR1 mRNA
      positive bands coextensive with laminae V/VI and II/III, respectively, and
      sparing lamina IV evolved during the first postnatal week, the grain density of
      which decreased during further postnatal development. Within the hippocampal
      formation, SSTR1 transcripts were initially observed at E18 in the subicular
      complex, and after birth also extending into the neighboring CA1 region. During
      the 1st and 2nd postnatal week, silver grains were observed over the pyramidal
      cell layer of CA2 and CA3 and as a faint supragranular band in the dentate gyrus.
      Similar to the isocortex, grain density decreased thereafter. Hypothetically, the
      pronounced temporospatial regulation of SSTR1 gene expression during brain
      development can be correlated with (1) the establishment and eventual reduction
      of transient cortical SSTergic neuron populations described for late pregnancy
      and early postnatal development and (2) a receptor subtype exchange during
      maturation as evidenced by the late (from postnatal day 7 onward) appearance of
      e.g. SSTR3.

PMID- 8575346
TI  - Programmed cell death enhances uniformity in rat cerebral hemispheres.
AB  - Programmed cell death (apoptosis) in rat cerebral hemispheres (CH) reportedly
      occurs around postnatal day 7 and kills 15-75% of all cells whose continuing
      presence would be of disadvantage for the organism: neurons erroneously
      connected, or supranumerary neurons that do not find targets and are not
      protected by neurotrophins. In the present paper we report that apoptosis (or a
      concomitant phenomenon) reduces also variability (coefficient of variation, CV)
      of CH parameters: weight, DNA content and protein content (presented here as a
      percent of the mean of each of these parameters). Postapoptotic brains have
      significantly lower CV of these parameters than the preapoptotic brains.
      Presumably, this trend toward uniformity offers selective advantages (for rat)
      and established itself during evolution. The mechanisms and the control of this
      phenomenon are at present largely unknown.

PMID- 8575345
TI  - The expression of myristoylated alanine-rich C-kinase substrate in
      oligodendrocytes is developmentally regulated.
AB  - Myristoylated alanine-rich C-kinase substrate (MARCKS), a major substrate of
      activated protein kinase C (PKC), is thought to be involved in PKC-mediated
      signal transduction events. In the present study, we have examined the expression
      of MARCKS in primary cultures of rat glial cells. Western blot analysis of
      different glial cell types (i.e., astrocytes, oligodendrocytes and microglia)
      revealed a relatively high level of MARCKS protein in oligodendrocytes. MARCKS
      protein and MARCKS mRNA levels in oligodendrocytes increased with time in
      culture, indicating a developmental regulation in MARCKS gene expression in
      differentiating oligodendrocytes. Immunocytochemical examination of developing
      oligodendrocytes indicated a strong labeling of MARCKS distributed both in the
      cell body and in the lacy network of processes. These findings, in concert with
      our previous observations on the role of PKC in oligodendrogenesis, strongly
      implicate a PKC-signaling system in oligodendrocyte development.

PMID- 8575347
TI  - Reproduction and caffeine consumption--a literature review.
AB  - Caffeine containing drinks are commonly consumed by pregnant women, but
      definitive studies concerning safety to the fetus are still awaited. This
      literature review highlights the methodological problems in mounting appropriate
      studies and assessing those publications that are available. Currently there is
      little to implicate caffeine consumption with congenital malformations or preterm
      delivery, but there may be associations with subfertility, miscarriage and
      intrauterine growth retardation. Definitive prospective studies are required.

PMID- 8575348
TI  - Volumetric analysis of the normal infant brain and in intrauterine growth
      retardation.
AB  - Twenty-eight infants with postmenstrual ages (PMA) in the range of 32-80 weeks
      were investigated. Twenty were newborn; among these the observed birth weight
      divided by the expected weight ranged from 0.31 to 1.1. Axial magnetic resonance
      images were recorded with a triple spin-echo sequence and the volumes were
      determined by encircling each structure of interest on every slice. Segmentation
      into grey matter, white matter and CSF was done by semi-automatic discriminant
      analysis. Growth charts for the cerebrum, cerebellum, corpora striata, thalami,
      ventricles, and grey and white matter are provided for infants with appropriate
      birth weight. The striatal (P = 0.02) and thalamic (P < 0.001) percentage of the
      hemispheric volume decreased with age, whereas the ratio of grey matter to white
      matter (G/W-ratio) increased (P = 0.01). In the neonatal patients, brain volumes
      were independently associated with both PMA and the degree of growth retardation.
      It was calculated that the hemispheric volume was reduced by from 16% to 23% if
      the total bodyweight was reduced by 40%. The G/W-ratio was found to be
      independently associated with the PMA (P < 0.05) and the degree of IUGR (P < 0.1)
      suggesting that fetal growth retardation reduces grey matter volume more than
      white matter.

PMID- 8575349
TI  - Maternal serum Schwangerschafts protein-1 (SP1) and fetal chromosomal
      abnormalities at 10-13 weeks' gestation.
AB  - Maternal serum SP1 concentration was measured at 10-13 weeks' gestation in
      samples from 87 pregnancies with fetal chromosomal abnormalities (trisomy 21 n =
      45; trisomy 18 n = 19; trisomy 13 n = 8; Turner syndrome n = 7; 47,XXX or 47,XXY
      n = 4; triploidy n = 4), and in samples from 348 matched controls. In the control
      group, SP1 increased significantly with fetal crown-rump length (r = 0.20, P <
      0.0001) and there was no significant association with fetal nuchal translucency
      thickness (r = 0.03). Similarly, in the group with fetal chromosomal
      abnormalities, SP1 increased significantly with crown-rump length (r = 0.31, P <
      0.01) and there was no significant association with nuchal translucency thickness
      (r = -0.08). In the groups with fetal trisomy 18 and trisomy 13, the median SP1
      (0.76 MoM and 0.57 MoM, respectively) was significantly lower than in the
      controls (z = 2.64 and z = 3.27, respectively); in 21% and 25% of the cases,
      values were below the 5th centile. In the group with trisomy 21 and other
      chromosomal abnormalities the median SP1 (0.96 MoM and 0.93 MoM, respectively)
      was not significantly different from controls (z = 1.17 and z = 0.67,
      respectively). Measurement of SP1 concentration at 10-13 weeks' gestation is not
      likely to be useful in the prediction of fetal chromosomal abnormalities.

PMID- 8575350
TI  - Muscle power, sitting unsupported and trunk rotation in pre-term infants.
AB  - Discrepancies between active and passive muscle power are often seen in pre-term
      infants over the first year. Generally of a transient nature, they are most
      obvious in the extensor muscles of the trunk where there is a high active muscle
      power relative to the passive component. While high active muscle power may not
      be a sign of cerebral palsy, it is our contention that it will impair functions
      such as unsupported sitting and the ability to rotate in this position. In this
      study, 20 full-term and 37 healthy pre-term infants were assessed at the
      (corrected) ages of 39 and 52 weeks for muscle power in the trunk, sitting
      unsupported and rotation around the body axis while seated. At the age of 39
      weeks, all full-term infants could sit without support. In contrast half of the
      pre-term infants could not sit without support and the majority of them could not
      rotate the trunk in this position. At 52 weeks the majority of pre-term infants
      could sit without support, despite having higher active muscle power in the
      trunk. However this deviant muscle power prevented rotatory movements of the
      trunk during sitting. The origin of this deviance may reside in the positioning
      to which pre-term infants are subjected after birth and thus postural management
      should be directed towards avoidance of extensor positions.

PMID- 8575351
TI  - The composition of individual molecular species of plasma phosphatidylcholine in
      human pregnancy.
AB  - The molecular species composition of plasma phosphatidylcholine (PC) was measured
      in sequential blood samples from 13 pregnant women from 16 weeks of gestation to
      delivery at term. The increased total plasma PC concentration at term was due
      solely to increased concentrations of individual species containing palmitate
      (16:0) rather than stearate (18:0) at the sn-1 position. The specific increase of
      PC16:0/22:6 concentration in mid-gestation suggests that adaptations to maternal
      hepatic PC metabolism may provide a mechanism to ensure adequate supply of 22:6(n
      3) to the fetus. While cord plasma PC was comparable to liver PC composition from
      three stillborn term infants, the compositions of these tissues differed from
      maternal plasma PC, which contained significantly more PC16:0/18:2 and
      PC18:0/18:2. These results suggest that, although fetal acquisition of
      polyunsaturated fatty acids (PUFA) is dependent on the maternal lipid supply, the
      detailed composition of fetal plasma PC may be regulated largely by intrinsic
      fetal mechanisms such as placental and liver PC metabolism. Similarly, the
      specific alterations to maternal plasma PC composition in pregnancy, which we
      postulate are associated with the supply of PUFA to the fetus, were substantially
      independent of variations in maternal dietary lipid nutrition.

PMID- 8575352
TI  - Changes of erythrocyte ouabain maximum binding after birth in neonates--in
      relation to erythrocyte sodium and potassium concentrations.
AB  - Erythrocyte ouabain maximum binding (Vmax level) represents the number of
      molecules of Na-K ATPase on the erythrocyte membrane. Erythrocyte Vmax levels and
      sodium potassium concentrations were studied in 38 mature and 57 premature
      infants, including 40 very low birth weight infants, 41 children and 16 adults,
      in order to clarify the development of erythrocyte Na-K ATPase related to mineral
      balance and thermogenesis. Vmax levels were the highest (22.9 +/- 8.9 nmol/l
      cells) for premature infants; correlated negatively with gestational age (r = 
      0.77, P < 0.01). Vmax levels correlated positively with the ratio of erythrocyte
      potassium to sodium concentration (IC-K/Na) at < 20 nmol/l cells of Vmax levels
      (r = 0.72, P < 0.01), but not at > or = 20 nmol/l cells (r = 0.23). Vmax levels
      in very low birth weight infants, especially < 28 weeks postconception, decreased
      gradually with postnatal days. Ln(Vmax) levels correlated negatively with
      postconceptional age (r = -0.75, P < 0.01). Under 28 weeks postconception, Vmax
      levels were high, but not correlated with IC-K/Na. It is probable that individual
      Na-K ATPase molecules may be less active, and the large numbers of Na-K ATPase
      molecules may compensate for the individual lower activity.

PMID- 8575353
TI  - Relaxin levels in amniotic fluid, extraembryonic coelomic fluid and maternal
      serum in early human pregnancy.
AB  - Separately identified samples of amniotic fluid and extraembryonic coelomic fluid
      together with maternal serum were collected from 22 women between 8 and 11 weeks
      of pregnancy and analysed for relaxin by immunoassay. Relaxin levels in maternal
      serum (median 1085 pg/ml; range 390-1259 pg/ml) were substantially higher than
      those in extraembryonic coelomic fluid (median 57.5 pg/ml; range 17-145 pg/ml; P
      < 0.0001; Mann-Whitney U-test). In turn, the levels of relaxin in coelomic fluid
      were higher than those in amniotic fluid (median 10 pg/ml; range 10-37 pg/ml; P <
      0.0001; Mann-Whitney U-test). A linear correlation was found between relaxin
      levels in maternal serum and coelomic fluid (r = 0.68; P = 0.001) but there was
      no relation between levels in the other fluid compartments.

PMID- 8575354
TI  - Human myotatic reflex development of the lower extremities.
AB  - Lower extremity (LE) myotatic reflexes were tested by percussion (taps) to the
      patellar and Achilles tendons. Surface electromyographic recordings were obtained
      from 5 LE muscles during tendon taps. Results indicated that LE myotatic reflexes
      underwent considerable change during early human development. The changes were
      non-linear and highly variable. Reflex irradiation (the presence of reflex
      responses in muscles other than the one being directly stimulated by a tendon
      tap) was present in the newborn but to a lesser extent than was in evidence later
      on during the first year of life. The percentage of time reflex irradiation was
      detected in heteronymous muscle groups appeared to achieve maximal levels during
      the first year and then progressively decline. The decline in reflex irradiation
      was most dramatic between the first and second years of life. Irradiated
      responses were still recorded from 2 year-old children but with less frequency
      than in children less than 1 year of age. With the exception of responses in
      muscles that were direct antagonists to the stimulated muscle, irradiation was
      not observed in children 3-5 years of age.

PMID- 8575355
TI  - What causes the excess left-handedness in twins?

PMID- 8575356
TI  - Modeling response of species to microcontaminants: comparative ecotoxicology by
      (sub)lethal body burdens as a function of species size and partition ratio of
      chemicals.
AB  - A model was designed and calibrated with accumulation data to calculate the
      internal concentrations of microcontaminants in organisms as a function of a few
      constants and variables. The main factors are the exposure time, the external
      exposure concentration, the partition ratio of the compound, and the size of the
      taxon concerned. The model was applied to calculate the lethal and sublethal body
      burdens of several priority compounds and some major taxa. Estimations were
      generally confirmed at the order of magnitude level by measured residues and
      applied doses if available. According to the estimations, most priority compounds
      chosen were critical for most taxa above internal concentrations of 0.1 mmol.kg-1
      wet wt. Trichloromethane, 1,2,4-trichlorobenzene, and hexachlorobenzene were
      lethal above this level only, whereas other organic microcontaminants affected at
      least some taxa at lower body burdens. The log(Kow) of the organic compounds
      ranged from 2.0 to 7.0. Keeping in mind that bioconcentration and -magnification
      ratios for metals may be quite variable, the lowest critical residues estimated
      were just below the value of 0.1 mmol.kg-1 wet wt. Here, external concentrations
      encountered in natural habitats seem to be a promising tool for predictive
      comparative ecotoxicology. The critical body burdens for plants and invertebrates
      may have been overestimated due to uncertainty about the parameters. Among the
      different taxa, however, the fish families chosen (Salmonidae and Cyprinidae)
      seem to be most sensitive to most compounds. Internal response concentrations of
      the herbicide atrazine were the lowest in micro- and macrophytes, whereas
      parathion affected invertebrates at low levels. The database that provided the
      external response concentrations was also consulted to estimate so-called
      extrapolation or safety factors. On average, long-term no effect concentrations
      in water are estimated to be about 10-30 times below short-term median lethal
      levels. In general, short-term versus long-term, lethal versus sublethal, and
      median versus no response concentration ratios each contributed factors of about
      2-3 to this overall ratio. The model for internal concentrations indicated that
      the ratio between the short-term and the long-term LC50 will be high for large
      species and high octanol-water partition ratios.

PMID- 8575357
TI  - A histochemical study of the biological effects of sodium dodecyl sulfate on the
      intestine of the gilthead seabream, Sparus aurata L.
AB  - This paper reports the morphological and histochemical changes caused by acute
      action of the detergent sodium dodecyl sulfate (SDS) on the intestine of the
      gilthead (Sparus aurata L.). Sixty-five giltheads were exposed to SDS
      concentrations of 5, 8.5, 10, and 15 mg/liter. Surface tensions were determined
      and the LC50 values calculated. The effects of SDS on the intestine were more
      pronounced in those specimens exposed to higher concentrations and for longer
      periods. Three causes of death were determined: (i) decrease in surface tension,
      (ii) destruction of tissue, and (iii) alteration of biomacromolecules. Both (ii)
      and (iii) were determined by histochemical techniques.

PMID- 8575358
TI  - Toxicity evaluations of wastewaters in Austria with conventional and cost
      effective bioassays.
AB  - The acute toxicity of 42 samples of different types of domestic and industrial
      discharges was assessed with a battery of tests comprising the standard Daphnia
      magna bioassay and three cost-effective new microbiotests (cyst-based Toxkits):
      the Rotoxkit F with the freshwater rotifer Brachionus calyciflorus and the
      Streptoxkit F and Thamnotoxkit F tests with the freshwater fairy shrimps
      Streptocephalus proboscideus and Thamnocephalus platyurus, respectively. Chemical
      analyses were performed for conventional water quality parameters such as
      chemical oxygen demand (COD), biological oxygen demand (BOD5), NO2, NH3, NH4+,
      O2, and pH. Toxicity of the samples, expressed as German regulatory G-values, was
      found to vary between 1 and 128. The results of these toxicity tests indicate
      that the Toxkit bioassays were as sensitive as the D. magna acute test. The
      crustacean T. platyurus was in 75% of the toxic samples more sensitive than D.
      magna. Relationships between the chemical composition and the toxicity of the
      discharges could be established in some cases, but not in others, which confirms
      the difficulties of extrapolating toxic hazards of complex wastes from (mostly
      restricted) chemical analyses. This study demonstrates the potential of cost
      effective bioassays (such as, e.g., cyst-based Toxkits) as attractive
      alternatives to (expensive) conventional bioassays for routine monitoring of
      effluents and wastes.

PMID- 8575359
TI  - Polarography as a tool in peptide and protein analysis: studies on metal
      chelating substances induced by cadmium in the algae Pheodactylum tricornutum and
      the graminae Agrostis capillaris.
AB  - Methods to determine characteristics and quantities of metal-binding substances
      are needed in order to identify phytochemical systems for use in agriculture and
      waste treatment. A metal-binding polypeptide (phytochelatin) was prepared by
      liquid chromatography from the algae Pheodactylum tricornutum and roots of the
      graminae Agrostis capillaris after exposure to cadmium. Polarographic
      (voltammetric) analysis indicated binding of cadmium by the polypeptide at
      different stabilities. No catalytic hydrogen peak at -1.7 V appeared in the
      polarogram of plant and algae metal-binding substance, but did appear in the
      polarogram of the metal-chelating protein metallothionein. In all polarograms,
      two significant peaks were detected. One at approximately -520 mV probably
      represents the reduction of single cadmium-sulfur bonds, and one at -930 mV the
      reduction of cadmium-thiolate complexes. A dose-response relationship between
      cadmium concentration and peak current at -930 mV was observed after exposure of
      roots of Agrostis at 5 and 10 microM.

PMID- 8575360
TI  - Acute toxicological effects in rats treated with a mixture of commercially
      formulated products containing methyl parathion and permethrin.
AB  - The study examined the interactions between a commercial formulation of methyl
      parathion (CF-MP) and a commercially formulated product of permethrin (CF-PMT) in
      male rats. The acute toxicity (LD50 values) and brain cholinesterase activity
      were investigated as toxicological endpoints. Results indicated that CF-MP
      modified the acute toxicity of CF-PMT. When animals were treated with a mixture,
      the addition of 380 mg/kg of CF-MP reduced the LD50 of CF-PMT by only 9.0%;
      however, when rats received CF-MP at 464 mg/kg, the LD50 of CF-PMT was reduced by
      37% (P < 0.001). Also, CF-PMT decreased the CF-MP-induced inhibition of
      cholinesterase activity by 50% (P < 0.05). It was interesting to observe that
      xylene, which is the most abundant component in the vehicle of both formulations,
      had no effect on the CF-MP-induced inhibition of the cholinesterase activity.
      There was no relation between lethality and the inhibition of the brain
      cholinesterase activity in rats treated with mixtures containing CF-MP+CF-PMT or
      with either commercially formulated product alone. Considering the increased
      toxicity observed in rats treated with CF-PMT+CF-MP, it would be advisable to
      investigate further the interactions between both pesticides.

PMID- 8575361
TI  - Microplate technique for screening and assessing cytotoxicity of xenobiotics with
      Tetrahymena pyriformis.
AB  - The microplate technique (MT) is developed and compared to the usual flask
      technique (FT) of Tetrahymena pyriformis GL cultures for assessing toxic effects
      of organic and inorganic substances on this ciliated protozoa model. Applied to
      the IC50 determination of 29 xenobiotics, the MT demonstrated good correlation
      with the FT (Y = 0.991X + 0.012, r = 0.94, P < 0.0001). The MT is rapid, easy-to
      handle, inexpensive, and statistically reliable and, so, may be helpful for
      screening investigations of water-soluble xenobiotics.

PMID- 8575362
TI  - Elevated copper levels during larval development cause altered locomotor behavior
      in the adult carabid beetle Pterostichus cupreus L. (Coleoptera: Carbidae).
AB  - It is generally believed that copper causes changes in carabid communities
      indirectly by reducing food availability, because these animals are frequently
      found to have only slightly elevated metal contents even close to pollution
      sources. Using computer-centered video tracking, the locomotor behavior of adult
      Pterostichus cupreus carabid beetles was quantified after being raised on copper
      contaminated food and soil during larval development. Copper was found to have an
      acute toxic effect measured in larval mortality, to cause a slight increase in
      the developmental period of males, but not to effect the emergence weights of
      adults of either sex. This toxic effect on the larvae was preserved through
      pupation to the surviving adults, which were normal in size and appearance, but
      displayed a dramatically depressed locomotor behavior. Copper analysis of these
      adults revealed that copper levels were either the same as or only slightly
      elevated in comparison with controls. The findings suggest that the altered
      locomotor behavior is associated with copper-induced internal structural damage
      during larval development and therefore expresses a prolonged or permanent
      effect. Such changes in locomotor behavior are likely to reduce the fitness of
      the animal under field conditions.

PMID- 8575363
TI  - Selenium assimilation and differential response to elevated sulfate and chloride
      salt concentrations in two saltgrass ecotypes.
AB  - A comparative study of selenium (Se) assimilation under the influence of sulfate
      and chloride salt salinity was conducted on two saltgrass ecotypes. The inland
      saltgrass grows successfully on the soil contaminated with elevated Se
      concentrations at Kesterson, Merced County, California. The coastal saltgrass
      colonizes a tidal salt marsh in Bodega Bay on the coast of California. The
      saltgrass samples were grown in sand culture and irrigated with quarter
      concentration of modified Hoagland solution supplemented with different
      concentrations of Se with or without sulfate or chloride salt. The Bodega Bay
      plants exhibited greater tolerance to both the sulfate and chloride salinity than
      the Kesterson plants. The plants of both ecotypes accumulated about 90% of their
      total tissue Se in the nonprotein fraction. When sulfate was present in the
      irrigation solution, the Kesterson plants assimilated significantly less Se in
      its protein and nonprotein fractions than in the Bodega Bay plants. Under Se
      treatment, chlorosis symptoms were found on the leaves of the Bodega Bay plants,
      but not on the leaves of the Kesterson plants. The above results demonstrate that
      the two saltgrasses are distinct ecotypes in respect to their salinity tolerance
      and the ability of mitigation of selenium assimilation in the presence of
      sulfate.

PMID- 8575364
TI  - Forest occurrence of Trichoderma species: emphasis on potential organochlorine
      (Xenobiotic) degradation.
AB  - Fungi of the genus Trichoderma are recognized as "keystone or controller"
      organisms in forest soils due to their involvement in decomposition and nutrient
      cycling and their regulation of associated mycoflora. Recent evidence has
      identified additional potential importance in the decomposition of xenobiotics.
      Both T. harzianum and T. viride have been shown capable of organochlorine
      degradation in vitro. During the 1990 growing season soil immersion tubes were
      employed to sample Trichoderma species growing in the forest floors of the
      Hubbard Brook Experimental Forest and of near-by Mount Moosilauke in New
      Hampshire. At Hubbard Brook, sample sites included a mature forest (100 years
      old) and a regenerating forest (5 years old). On Mount Moosilauke, sample sites
      included haplorthod and cryofolist soil types and low, medium, and high
      elevation. T. harzianum was isolated from both sites in relatively high amount.
      T. viride was also present at both sites but in relatively low amount. T.
      polysporum was consistently isolated at all elevations but in relatively low
      amount. The abundance of T. harzianum decreased with increasing elevation, while
      the abundance of T. viride increased with increasing elevation. The evidence
      presented is consistent with other studies stressing the high spatial variability
      of members of this genus. Causes of this variability are presumed to be numerous
      and involve abiotic and biotic forces. Persistence of organochlorine contaminants
      in northern forest soils may be influenced by the abundance of fungal degraders
      such as T. harzianum and viride.

PMID- 8575365
TI  - Effects of azinphos-methyl on the reproductive success of the bluegill sunfish,
      Lepomis macrochirus, in littoral enclosures.
AB  - Adult bluegills were exposed to a single application of azinphosmethyl in 12
      littoral enclosures in a northern Minnesota pond. Responses measured were adult
      behavior and spawning, embryo hatchability, larval survival until swim-up, young
      of-year (Y-O-Y) growth, and total biomass. Four enclosures each were treated at
      1.0 and 4.0 micrograms/liter and four remained untreated. The half-life of
      azinphos-methyl was 2.3 and 2.4 days at each of the two treatment levels,
      respectively. Quantifiable residues remained in the water for 8 days.
      Concentrations of 4.0 or 1.0 microgram/liter did not cause any significant long
      term (63 day) effects on bluegill reproduction, embryo hatchability, larval
      survival, growth, or biomass. Although important bluegill prey such as copepod
      nauplii and cladocerans were significantly or greatly reduced by Day 7 following
      treatment, they recovered to levels equal to or greater than some of the control
      enclosures by Day 35. The apparent lack of significant long-term effects on
      reproductive success can be partially explained by the relatively short half-life
      of azinphos-methyl in littoral enclosures.

PMID- 8575366
TI  - Increased polycyclic aromatic hydrocarbon toxicity following their
      photomodification in natural sunlight: impacts on the duckweed Lemna gibba L. G
      3.
AB  - The authors previously demonstrated that simulated solar radiation (SSR), with a
      fluence rate of only 40 mumol m-2 sec-1, increased polycyclic aromatic
      hydrocarbon (PAH) toxicity to the duckweed Lemna gibba and that PAHs
      photomodified in SSR (generally oxygenation of the ring system) are more toxic
      than the parent compounds (Huang et al., Environ. Toxicol. Chem., 1993, 12, 1067
      1077). It is not known, however, to what extent toxicity of PAHs can increase due
      to photomodification. Thus, natural sunlight, which has a high fluence rate
      (approximately 2000 mumol m-2 sec-1), was used to photomodify anthracene,
      benzo[a]pyrene, fluoranthene, phenanthrene, and pyrene. Toxicity was based on
      growth inhibition of L. gibba, measured as the rate of production of new leaves
      over an 8-day period. Initially, the toxicity of the PAHs applied in intact form
      was probed, with the compounds demonstrating greater toxicity in sunlight than in
      SSR. Next the PAHs were photomodified in sunlight prior to incubation with the
      plants. The half-lives of the PAHs in sunlight ranged from 12 min to 30 hr.
      Although most of the products of PAH photomodification are not yet identified,
      the degree that PAH toxicity increased following photomodification in sunlight
      could still be probed. The mixtures of photomodified chemicals that were derived
      from each PAH in sunlight were applied of L. gibba and growth inhibition under
      100 mumol m-2 sec-1 of SSR was determined. The LC50s for the PAH photoproducts
      generated in sunlight were an order of magnitude lower than the LC50s for the
      PAHs applied in intact form.

PMID- 8575367
TI  - Use of the bioluminescent bacterium Vibrio harveyi to detect biohazardous
      chemicals in soil and water extractions with and without acid.
AB  - An investigation was undertaken using the bioluminescence-reduction bioassay of
      Vibrio harveyi to study the toxicity of 31 chemicals in a soil and water
      extraction that was treated with and without hydrochloric acid. Soil had the
      chemical added and was washed with 0.2 N HC1 and afterward this acid-treated soil
      containing the chemical was evaluated. Each chemical was tested independently.
      Endpoints determined were either an estimated effective concentration at 50 or
      20%, which was based on bacterial-luminescence remaining after treatment. This
      investigation suggests that metals are more effectively bound in treatments
      without acid than those with acid, while no difference in toxicity was observed
      for organics. In comparison to a previous study of toxicity using these chemicals
      in water, soil was effective in reducing toxicity as determined by this assay.
      However, each chemical appears to have its own unique toxicity characteristic
      when evaluated under different conditions.

PMID- 8575368
TI  - Transendoscopic electrocautery-induced gastric ulcers as a model for gastric
      healing studies in ponies.
AB  - The ponies were apparently healthy and 6-20 months of age. In Study 1, gastric
      lesions were created by transendoscopic electrocautery in the non-glandular
      gastric mucosa, adjacent to the margo plicatus in 9 ponies which were then
      treated with water, 12 mg cimetidine HCl/kg bwt or 18 mg cimetidine HCl/kg bwt
      per os every 12 h for 35 days. In Study 2, gastric lesions were similarly induced
      in 9 ponies in the non-glandular mucosa and also in the glandular mucosa just
      below the non-glandular lesion on the greater curvature of the stomach. The
      ponies were treated with water, 8 mg cimetidine/kg bwt or 16 mg cimetidine/kg bwt
      per os every 8 h for 21 days. In both studies gastric lesion healing was
      monitored twice weekly by video gastroscopy. There was no apparent difference in
      healing times between the water and cimetidine treatment groups in either study.
      These results indicate that uniform gastric ulcers can be created by
      transendoscopic electrocautery in the non-glandular mucosa of ponies and that
      these ulcers heal at a predictable rate which should be useful in studying
      compounds that might accelerate healing of gastric mucosal lesions. However,
      cimetidine was not effective in accelerating the rate of healing under the
      conditions of this study.

PMID- 8575369
TI  - Serological and microbiological findings on 3 farms with equine leptospiral
      abortions.
AB  - Blood and urine samples from horses on 3 central Kentucky horse farms with prior
      histories of leptospiral abortions were analysed. Blood samples were obtained
      from all available horses on each farm and tested for antibodies to 6 leptospira
      serovars. Urine samples were collected from non-gravid mares with serum antibody
      titres > or = 1:800 and examined for leptospires by dark-field microscopy,
      fluorescent antibody testing and culture. Adult horses had the greatest
      serological evidence of exposure to leptospira, followed by yearlings, then
      foals. Of horses with anti-leptospiral antibodies, 76.3% reacted against serovar
      bratislava, 49.1% against icterohaemorrhagiae, 20.1% against grippotyphosa, 16.3%
      against pomona genotype kennewicki, 15.9% against hardjo and 1.0% against
      canicola. These findings confirmed that horses in central Kentucky are exposed to
      multiple leptospira serovars. The seroprevalence of antibodies to the 6 selected
      serovars was consistent among the 3 selected farms. There was no direct
      correlation between the serovar that was the cause of abortion in the previous
      season and prevalence of positive titres to that serovar in horses tested on the
      farms in the following year. Furthermore, there was no evidence of long-term
      urinary shedding of leptospira by horses with high leptospira antibody titres.

PMID- 8575370
TI  - Scintigraphic measurement of uterine clearance in normal mares and mares with
      recurrent endometritis.
AB  - The percentage of Technetium 99m-albumin colloid (99mTc-microAA), a radiocolloid,
      cleared from the uterine lumen within 4 h of intrauterine infusion, was measured
      in 15 mares during 2 consecutive cycles, on Day 3 of oestrus and 48 h after
      ovulation. Four nulliparous (Group 1) and 4 multiparous (Group 2) mares were
      classified as resistant and the remaining 7 multiparous mares were classified as
      susceptible (Group 3) to endometritis. Mares in Groups 1 and 2 cleared more 99mTc
      microAA from their uteri than did mares in Group 3 during oestrus (P < 0.01) and
      48 h after ovulation (P < 0.001). In the Group 1 + 2 mares, > 50% of the colloid
      was cleared in 7 and none in the remaining mare, apparently related to lack of
      cervical relaxation. Mean percentage of 99mTc-microAA cleared by Group 3 mares
      was negligible (< 5%), but some 99mTc-microAA was cleared by 3 of the 7 mares
      during 4 of the 6 studies conducted. Clearance of radiocolloid infused into the
      uterus of 3 reproductively normal mares during dioestrus was negligible. 99mTc
      microAA infused into the uterus did not adversely affect endometrial integrity as
      determined by endometrial biopsy. Mares tolerated the procedures well. We
      conclude that scintigraphy can be used to detect impaired mechanical clearance of
      the uterus: reproductively normal mares clear > 50% 99mTc-microAA within 2 h of
      infusion whereas those susceptible to endometritis or mares with poor cervical
      dilatation may exhibit delayed uterine clearance.

PMID- 8575371
TI  - Evaluation of pulse oximetry in horses surgically treated for colic.
AB  - All 43 horses anaesthetised for colic surgery were premedicated with xylazine or
      diazepam. Anaesthesia was induced with guaifenesin and ketamine, horses were
      placed in dorsal recumbency and anaesthesia was maintained with isoflurane in
      oxygen and mechanical ventilation. Haemoglobin saturation readings (SpO2) were
      taken with a pulse oximeter and compared with computed haemoglobin saturation
      (SaO2) from arterial blood samples. Readings were taken over a range of SaO2 of
      78-100%, mean arterial blood pressure ranged from 24 to 108 mmHg and PaO2 ranged
      from 53 to 490 mmHg. Analysis of 107 readings showed that SpO2 values predicted
      SaO2 but time, blood pressure and individual horse did not. Correlation
      coefficients between SpO2 and SaO2 were 0.85 for all values and 0.88 for values
      at 30 min. Values for bias and precision were calculated for all SpO2 values and
      for readings separated into 3 saturation groups: normal, low normal, and
      abnormal. The pulse oximeter tended to underestimate SaO2 at all times, and was
      less precise as the saturation decreased.

PMID- 8575372
TI  - Plasma lactate response to submaximal and maximal exercise tests with training,
      and its relationship to performance and muscle characteristics in standardbred
      trotters.
AB  - Seven young Standardbred trotters, born, raised and trained at the same camp,
      performed submaximal and maximal work tests on a track. The submaximal test
      consisted of four 1,000 m runs at the trot, with increasing speed at each run.
      Each horse performed this test when 24, 26, 29 and 40 months old. The maximal
      test consisted of trotting 1,600 m and was performed at 24 and 29 months of age.
      Blood samples for plasma lactate analyses were obtained after each run, during
      the submaximal test and after the maximal test. Muscle biopsy samples were
      obtained at 24 and 29 months of age. The results showed marked individual
      differences in lactate response to submaximal effort. Early training only
      appeared to influence plasma lactate response in some horses. After 40 months of
      age the lactate response to the final submaximal test was significantly lower
      (7.2 mmol/l) than at 29 months (14.5 mmol/l). A negative correlation was found
      between lactate concentration after all runs in the submaximal test, and the
      horses speed over 1,600 m. No correlations were found between lactate
      concentration after the maximal test and the horses' speed. The activity of
      citrate synthase, a marker for muscle oxidative capacity, increased from 24 to 29
      months of age. The proportion of Type IIB fibres decreased, whereas that of Type
      I fibres increased. It is concluded that lactate response to a submaximal work
      test on a track can be an important tool for evaluating performance capacity of
      an individual horse.

PMID- 8575373
TI  - Investigation of association between alpha-1 proteinase inhibitor haplotype and
      endometritis in the thoroughbred mare.
AB  - Failure to inhibit proteinases can lead to excessive tissue damage. The
      possibility that the severity of endometritis in Thoroughbred mares correlates
      with the haplotypes of plasma alpha 1-proteinase inhibitor (alpha 1-PI) expressed
      was investigated in two groups of mares. In mares with pyometritis before
      treatment, the frequency of the N haplotype, which is already high in the
      Thoroughbred population, was significantly increased when compared with that in a
      large published population. In mares with acute endometritis which persisted
      after treatment followed by sexual rest, the absence of S and T haplotypes was
      significant, suggesting that, when present, they may have a protective function.

PMID- 8575374
TI  - Evaluation of partial arytenoidectomy as a treatment for equine laryngeal
      hemiplegia.
AB  - The efficacy of partial arytenoidectomy was assessed in 6 Standardbred horses,
      with surgically induced laryngeal hemiplegia, at rest (Period A) and during
      exercise at speeds corresponding to maximum heart rate (Period C) and 75% of
      maximum heart rate (Period B). Peak expiratory and inspiratory airflow rate (PEF
      and PIF), and expiratory and inspiratory transupper airway pressure (PUE and PUI)
      were measured and expiratory and inspiratory impedance (ZE and ZI) were
      calculated. Simultaneously, tidal breathing flow-volume loops (TBFVL) were
      acquired using a respiratory function computer. Indices derived from TBFVL
      included airflow rates at 50 and 25% of tidal volume (EF50, IF50, EF25, and IF25)
      and the ratios of expiratory to inspiratory flows. Measurements were made before
      left recurrent laryngeal neurectomy (baseline), 2 weeks after left recurrent
      laryngeal neurectomy (LRLN) and 16 weeks after left partial arytenoidectomy
      coupled with bilateral ventriculectomy (ARYT). After LRLN, during exercise
      Periods B and C, Z1 and the ratio of EF50/IF50 significantly increased and PIF,
      IF50 and IF25 significantly decreased from baseline values. At 16 weeks after
      ARYT, Z1 returned to baseline values during Periods B and C. Although PIF, IF50,
      IF25, PEF/PIF, and EF50/IF50 returned to baseline values during Period B, these
      indices remained significantly different from baseline measurements during Period
      C. After ARYT, TBFVL shapes from horses during Period C approached that seen at
      the baseline evaluation. Partial arytenoidectomy improved upper airway function
      in exercising horses with surgically induced left laryngeal hemiplegia, although
      qualitative and quantitative evaluation of TBFVLs suggested that some flow
      limitation remains at near maximal airflow rates. These results indicate that,
      although the procedure does not completely restore the upper airway to normal,
      partial arytenoidectomy is a viable treatment option for failed laryngoplasty and
      arytenoid chondropathy in the horse.

PMID- 8575375
TI  - Studies on the transport in vitro of lysine, histidine, arginine and ammonia
      across the mucosa of the equine colon.
AB  - Discs of stripped mucosa from the proximal ventral colon were prepared
      immediately after slaughter of 8 Shetland cross-breed ponies. The mucosae were
      fixed in incubation chambers and used in incubation experiments to study the
      transmucosal fluxes of the amino acids lysine, histidine and arginine (150 min)
      and of ammonia (90 min). When the amino acid concentrations in the mucosal
      solution were in the physiological range (2.8-3.0 mmol/l) no transport to the
      serosal side of the tissue was found. When the concentrations were raised 10
      fold, less than 2% of the mucosal amino acid pool was recovered in the serosal
      solution. Ammonia was transported across the mucosa at significant rates although
      only 63% of the ammonia that disappeared from the mucosal solution was found in
      the serosal solution. The findings show that the equine proximal colon is
      virtually impermeable to luminal free amino acids whereas ammonia is transported
      at rates equal to, or higher than those observed with rumen mucosa from sheep.

PMID- 8575376
TI  - Immunoreactive insulin-like growth factor I and insulin in blood plasma and milk
      of mares and in blood plasma of foals.
AB  - Concentration of (total) globulin was relatively stable in blood plasma of mares,
      but rapidly decreased in colostrum to very low levels within 2 days after
      parturition. In foals, after intake of the first colostrum, globulin increased
      within 1 day in blood plasma, but remained at lower concentrations than those
      measured in mare plasma. Concentrations of immunoreactive insulin (iI) were high
      during the first 2 months of lactation in blood plasma of mares and then
      decreased, were high in first colostrum and then decreased drastically, and
      remained at low concentrations up to weaning in blood of foals. In mares,
      concentration of immunoreactive insulin-like growth factor I (iIGF-I) in plasma
      increased during late pregnancy, peaked 2 days after parturition, and then
      gradually declined until weaning. iIGF-I was highest in first colostrum and then
      dramatically decreased within the first 2 days of lactation. In foals, iIGF-I
      gradually increased over the first 2 months of life. IGF-I in the horse appears
      to be bound to proteins of similar molecular weight as in cattle. The study
      demonstrates different patterns of changes in plasma iIGF-I and iI concentrations
      in mares and their foals, whereas iI, iIGF-I and globulin changes in colostrum
      and milk occurred in parallel. Furthermore, plasma iI and iIGF-I behaved
      differently, while colostrum iI and iIGF-I behaved similarly, in mares compared
      with dairy cows.

PMID- 8575377
TI  - The prevalence of latent Equid herpesviruses in the tissues of 40 abattoir
      horses.
AB  - Equid herpesviruses 1 or 4 (EHV-1 or -4) were isolated by cocultivation from 60%
      of 40 horses examined at slaughter. The lymph nodes draining the respiratory
      tract were the most common source of virus. EHV-1 or EHV-4 was never isolated
      from the trigeminal ganglia (SLG). The polymerase chain reaction (PCR) detected
      virus in 87.5% of bronchial lymph nodes and a similar level in the trigeminal
      ganglia that were examined. By both assays approximately one third of the
      positive animals harboured both viruses. Equid herpesvirus 2 (EHV-2) was isolated
      from all but one of the horses and from > 75% of the lymph nodes draining the
      respiratory tract; alpha viruses were isolated only in the presence of EHV-2. The
      results indicate that latent EHV-1 and EHV-4 are widespread in the equine
      population and that the primary site of latency is the lymph nodes of the
      respiratory tract.

PMID- 8575378
TI  - Geographical variation of seropositivity to Ehrlichia risticii (equine monocytic
      ehrlichiosis) of horses in New York state.
AB  - A total of 2,579 serum samples from horses in New York state during 1985-1986
      were examined for seropositivity to Ehrlichia risticii using the indirect
      fluorescent antibody technique. Cluster analysis statistical technique was used
      to group counties according to their estimated EME-disease rate (seropositive
      proportion of sampled horses). Counties were clustered into 4 groups of different
      EME-disease rates, representing high (86% seropositive), medium (66%
      seropositive), medium-low (47% seropositive) and low (6% seropositive) risk
      regions. The logistic regression statistical technique was used to examine
      whether the geographic variation of E. risticii seropositivity is due to other
      EME-risk factors. Risk factors known to be associated with EME (age, breed, sex,
      month of sample submission) have not contributed to the apparent geographical
      variation of the disease in New York state. This lack of an association between
      equine host factors or temporal factors with the geographical variation of EME
      suggests that conditions necessary for establishment of EME endemic foci involves
      other factors. The county equine population density and presence of a major
      equine racetrack were not associated with the geographical variation of the
      disease in New York state. The high risk regions for EME were located
      predominately along river valleys, but an explanation of why EME activity varies
      geographically remains speculative.

PMID- 8575380
TI  - Progression and association with lameness and racing performance of radiographic
      changes in the proximal sesamoid bones of young standardbred trotters.
AB  - Radiographic examination of the metacarpo- and metatarsophalangeal joints was
      performed on 753 Standardbred trotters (6-21 months of age): 21 showed obvious
      changes in 26 proximal sesamoid bones on lateromedial projection. The
      radiographic changes were divided into 6 different types: (1) irregular abaxial
      margin (8 horses); (2) enlargement of the sesamoid bone (6 horses); (3)
      'fracture' or separate centre of ossification of the apex (4 horses); (4)
      vertical, non-articular fracture of the plantar part of the sesamoid bone (1
      horse); (5) a small bony fragment located in a defect in the apical part of the
      bone (2 horses); and (6) multiple areas of decreased radiodensity (1 horse). Each
      horse displayed only one type of radiographic change except for one which
      possessed those of types 3 and 5. Follow-up radiographic examination of 21 of the
      26 affected proximal sesamoid bones at approximately 6-month intervals revealed a
      reduction in the changes in 13 bones and an unaltered condition in 8. Lameness
      examination was performed on 16 of the 21 horses at 3 years of age and 14 (87.5%)
      were observed to be lame, but detected lameness did not seem to be referrable to
      the sesamoid changes. Earnings after the racing season as 3- and 4-year-old
      horses showed no differences (P > 0.05) between horses with radiographic changes
      in the proximal sesamoid bones and those without such changes.

PMID- 8575379
TI  - Identification of 2 stallion sperm-specific proteins and their autoantibody
      response.
AB  - In this study, 2 stallions were immunised with their own spermatozoa to ascertain
      whether an antisperm autoantibody response could be mounted. The results
      demonstrated that the stallion can recognise and respond to sperm autoantigens by
      producing circulating antisperm antibodies, primarily of the IgG class. Such
      autoantibodies appeared 2-4 weeks after inoculation and persisted for 6-20 weeks.
      Immunochemical characterisation by western blot identified two major sperm
      autoantigens, with molecular weights of 70 kD and 62 kD. Control pony stallions
      immunised with adjuvants alone failed to exhibit such antibodies. IgA antisperm
      antibodies were measurable in seminal plasma of both stallions. We suggest that,
      as in other species, autoimmunity to spermatozoa may play a role in idiopathic
      subfertility in stallions.

PMID- 8575381
TI  - An ultrastructural study of intranuclear bodies in granular epithelial cells of
      the equine small intestine.

PMID- 8575383
TI  - Congenital choanal restriction in 3 horses.

PMID- 8575382
TI  - Preliminary studies of recombinant bovine granulocyte-colony stimulating factor
      on haematological values in normal neonatal foals.

PMID- 8575384
TI  - Ventral glottic stenosis in 3 horses.

PMID- 8575385
TI  - Bilateral keratoconjunctivitis sicca in a horse.

PMID- 8575386
TI  - How important are leptospiral infections as a cause of equine disease?

PMID- 8575387
TI  - Proteolysis and antiproteolysis--a delicate balance.

PMID- 8575388
TI  - Laryngeal surgery--the way ahead.

PMID- 8575389
TI  - Fracture of the wing of the ilium, adjacent to the sacroiliac joint, in
      thoroughbred racehorses.
AB  - During a two year period, sagittal fractures of the wing of the ilium were
      diagnosed in 10 Thoroughbred horses. All were spontaneous fractures sustained
      during normal exercise in training and racing, with no history of inciting
      trauma. When ultrasound scans of the surface of the pelvis were performed, the
      fracture was clearly visible as a discontinuity of the sacral wing of the ilium.
      In 3 horses, an irregular contour suggestive of periosteal callus was seen in the
      vicinity of the acute fracture. All horses examined by gamma scintigraphy had a
      focal increase in uptake of isotope just lateral to the tuber sacrale. Nine of
      the horses were treated conservatively by rest. The other horse had bilateral
      fractures and was subjected to euthanasia at the time of the injury. Six horses
      returned to full training, and 2 subsequently won, without recurrence of
      lameness.

PMID- 8575390
TI  - Differential scanning calorimetry (DSC): protein structure probe useful for the
      study of damaged tendons.

PMID- 8575391
TI  - Anecdotes and clinical trials: the story of clenbuterol.

PMID- 8575392
TI  - The Equine Virology Research Foundation--a view from abroad.

PMID- 8575393
TI  - Joint structure, biochemistry and biochemical disequilibrium in synovitis and
      equine joint disease.

PMID- 8575394
TI  - Oxytocin enhances clearance of radiocolloid from the uterine lumen of
      reproductively normal mares and mares susceptible to endometritis.
AB  - The effects of oxytocin on the percentage of technetium 99m albumin colloid
      (99mTc-microAA), cleared from the uterine lumen was measured in 13 mares.
      Scintigraphy was performed during 4 consecutive oestrous cycles, on Day 3 of
      oestrus during Cycles one and 3 and 48 h after ovulation during Cycles 2 and 4.
      Oxytocin (20 iu) was given i.v. after the initial scintigraphy image during
      Cycles 3 and 4. Seven multiparous mares (Group 1) were classified as
      'susceptible' and 6 mares (2 nulliparous and 4 multiparous; Group 2) were
      classified as 'resistant' to endometritis. All mares cleared > 90% of 99mTc
      microAA within 30 min of oxytocin injection. When no drug was given, Group 1
      mares cleared negligible amounts of radiocolloid (< 5%) and Group 2 mares cleared
      50-80%. No mares showed signs of colic after oxytocin administration. It is
      concluded that oxytocin enhances uterine clearance of radiocolloid and may be
      useful for treating mares exhibiting impaired uterine clearance.

PMID- 8575395
TI  - Endoscopic anatomy and map of the equine bronchial tree.
AB  - To develop a bronchoscopic map of the equine respiratory tree, the major airways
      of the lungs of 6 healthy Thoroughbred horses were systematically explored with a
      flexible fibreoptic endoscope through a tracheostomy while the horses were
      sedated in stocks. With the carina as the reference point, measurements were made
      of distances to the branches of the major airways using markers on the shaft of
      the endoscope. All branches were explored until the narrowing of their diameters
      prevented further advancement of the endoscope. Positions of origins of branches
      from the parent bronchus were recorded in relation to a 12 h clock. Branching
      patterns of the right and left lungs were similar. Seventeen branches of the
      principal and caudal lobar bronchi of the left lung, and 18 branches of the
      principal and caudal lobar bronchi of the right lung were identified. Mean
      explorable distances from the carina to the ends of the right and left caudal
      lobar bronchi were 34.0 +/- 3.5 (sd) and 34.5 +/- 3.0 cm, respectively.
      Generally, smaller horses had shorter explorable bronchial lengths. Branching
      patterns of the parent bronchi were fairly consistent among horses, particularly
      the branches closest to the carina. After endoscopy and euthanasia, the lungs
      were removed, and dried with pressurised air flowing through them for 7-10 days.
      Attempts to explore the airways of the dried lungs endoscopically were relatively
      unsuccessful, because airways were much smaller in the dried lungs, and many of
      the branches were distorted when compared with their antemortem appearances.
      However, having a dried lung specimen as a reference during the bronchoscopic
      procedure was useful for maintaining orientation in the lungs. Radiographs were
      used to estimate the location of the origin and destination of each airway branch
      in relation to the nearest intercostal space. This makes the airway map useful
      when lesions identified radiographically are to be lavaged.

PMID- 8575396
TI  - Differential scanning calorimetric studies of superficial digital flexor tendon
      degeneration in the horse.
AB  - Differential scanning calorimetry (DSC) of equine superficial digital flexor
      tendons revealed the presence of a small exothermic peak at 23 degrees C of
      unknown origin, and a large endothermic peak at 70 degrees C due to denaturation
      of cross-linked collagen fibres. In the central degenerated core of damaged
      tendons the denaturation temperature remained at 70 degrees C but the enthalpy
      decreased in relation to the extent of degeneration of the tendon. We suggest
      that this reduction in enthalpy is due to depolymerisation and denaturation of
      the collagen fibres. This contention is supported by the observed increased
      activity of the degradative enzyme cathepsin B secreted by the fibroblasts. DSC
      analysis of cultured porcine tendon fibroblasts revealed a multicomponent
      endotherm, denaturation beginning at 46 degrees C, a temperature capable of being
      achieved within the tendon during intensive exercise. DSC clearly has
      considerable potential in complementing morphological and biochemical studies to
      determine the aetiology and progress of equine tendon degeneration.

PMID- 8575397
TI  - An investigation of the proteoglycan metabolism of mature equine articular
      cartilage and its regulation by interleukin-1.
AB  - The effect of human recombinant interleukin-1 beta (rhIL-1 beta) on proteoglycan
      metabolism was investigated in cultures of full thickness explants of articular
      cartilage from horses 3-21 years of age. Proteoglycan synthesis was inhibited at
      all ages but no alteration in the hydrodynamic size or electrophoretic
      heterogeneity was observed in proteoglycan isolated from rhIL-1 beta stimulated
      cartilage. The sulphation pattern of the newly synthesised proteoglycan molecules
      was, however, significantly affected by the presence of the peptide regulatory
      factor. Interleukin-1 had no effect on the rate of turnover of newly synthesised
      or endogenous proteoglycans in mature equine articular cartilage and did not
      influence the structure of proteoglycan fragments released into the culture
      medium. These observations suggest that IL-1, released into synovial fluid during
      inflammation, may modify the proteoglycan composition of normal equine cartilage
      not by stimulating catabolic enzymes capable of degrading the resident
      proteoglycans but by promoting the deposition of a reduced number of newly
      synthesised proteoglycan molecules of abnormal composition.

PMID- 8575399
TI  - Haematological, bone marrow and clinical chemical changes in neonatal foals given
      canine recombinant granulocyte-colony stimulating factor.
AB  - Five Thoroughbred and Quarter Horse cross foals were given 20 micrograms canine
      recombinant granulocyte-colony stimulating factor (rcG-CSF) per kg bwt
      intramuscularly (i.m.) on the day of birth and 10 micrograms rcG-CSF/kg for 13
      additional days. During this time and for an additional 21 days haematology, bone
      marrow and clinical chemical analyses were performed. After one day of rcG-CSF
      administration leucocyte and neutrophil counts increased from 9.16 x 10(9)/l to
      23.44 x 10(9)/l and from 6.45 x 10(9)/l to 19.61 x 10(9)/l, respectively. The
      counts continued to increase for the next 3-4 days and then there was a slight
      decrease. A second increase followed and the leucocyte and neutrophil counts
      increased to 52.84 x 10(9)/l and 45.16 x 10(9)/l on the day after the last rcG
      CSF administration (Day 15). The counts decreased rapidly immediately after the
      administration of rcG-CSF was stopped and then at a slower rate. The cell counts
      were still higher than in the controls at the end of the study period (Day 35).
      Bone marrow cellularity increased from 10-25% before rcG-CSF was given to 60-80%
      after 5 days. The increase in cellularity was due to increased myeloid activity
      because the myeloid to erythroid ratio increased from 2.7 to 8.8. Serum chemistry
      changes were minimal although foals given rcG-CSF at various times had lower
      glucose concentrations and increased alkaline phosphatase and gamma glutamyl
      transferase activities.

PMID- 8575398
TI  - The structure, innervation and location of arteriovenous anastomoses in the
      equine foot.
AB  - In the foot of the horse, arteriovenous anastomoses (AVAs) of epithelioid type
      occurred in the dermis of the coronary band, in the coronary and terminal
      papillae, in neurovascular bundles and at the entrance to and along the length of
      the dermal laminae. A particular feature of the epithelioid segment of AVAs in
      the horse, compared with that of other species, was the height and surface
      complexity of many of the endothelial cells. They extended into the lumen,
      forming undercut and tunnel-like areas which correlated with the characteristic
      surface marking of AVAs observed in vascular casts. The number of cell
      organelles, including the concentration of vesicles in the luminal cytoplasm,
      suggested cells with a high metabolic activity. The luminal surface possessed
      numerous microvilli and long cytoplasmic cell processes which appeared to
      surround material in the lumen. The innervation of AVAs was more dense than that
      of the arteries and consisted of adrenergic and peptidergic nerves. Noradrenaline
      and neuropeptide Y-containing nerves were identified as the vasoconstrictor
      components of the nerve supply and occurred along arteries and formed dense
      plexuses around AVAs. Calcitonin gene-related peptide, substance P and vasoactive
      intestinal polypeptide are vasodilators and were present in single nerve fibres
      which accompanied arteries and AVAs along the length of the dermal laminae. In
      this study the distribution, density and innervation of AVAs in the equine foot
      are correlated with their proposed role in the development of acute laminitis.
      The release of vasoactive peptides from diseased organs remote from the foot may
      induce inappropriate prolonged dilatation of AVAs and thus contribute to the
      laminar ischaemia of acute laminitis.

PMID- 8575400
TI  - Skeletal muscle characteristics in red blood cell normovolaemic and hypervolaemic
      standardbred racehorses.
AB  - Muscle biopsy specimens from the middle gluteal muscle were studied in 16 red
      blood cell hypervolaemic (Group HV) and 19 normovolaemic (Group NV) Standardbred
      racehorses. All horses were stallions, 4-8 years old and having similar mean
      racing performance values, as described by an individual selection index value.
      All horses raced regularly but those in Group HV did not perform as expected and
      were therefore referred to the clinics for exercise tolerance testing. Muscle
      biopsy specimens were analysed for fibre type distribution (Type I, IIA and IIB),
      fibre area and relative fibre area. In addition, oxidative capacity of the fibres
      was evaluated by staining for nicotinamide adenine dinucleotide (NADH)
      tetrazolium reductase, and the activities of citrate synthase, 3-OH-acyl CoA
      dehydrogenase and lactate dehydrogenase were analysed in whole-muscle samples.
      With the exception of a higher percentage of Type IIB fibres in Group HV having a
      high oxidative capacity as evaluated by the NADH stain, no significant difference
      were found in fibre composition, fibre area or enzyme activity between the Groups
      HV and NV.

PMID- 8575401
TI  - An examination of the occurrence of surgical wound infection following equine
      orthopaedic surgery (1981-1990).
AB  - Post operative surgical wound infection rates were determined 452 cases of equine
      orthopaedic surgery performed at the Western College of Veterinary Medicine,
      Saskatoon, Saskatchewan, between January 1, 1981 and December 31, 1990. Only
      surgical procedures classified as clean or clean-contaminated by the National
      Research Council were included in this study. The overall post operative
      infection rate was 10.0% (45 of 452). Clean surgeries (n = 433) had an 8.1%
      infection rate while clean-contaminated surgeries (n = 19) had a 52.6% infection
      rate. Information collected from the medical records was used in univariate and
      multivariate logistic regression models to evaluate significant determinates of
      post operative infection. Significant determinates of post operative infection
      were: surgical classification, orthopaedic involvement, duration of surgery,
      administration of preoperative antibiotics and gender. Clean-contaminated
      surgeries had an increased risk of infection compared to clean surgeries (odds
      ratio (OR) = 24.3), procedures involving long bones had an increased risk of
      infection compared to procedures involving articular surfaces (OR = 5.1),
      surgeries lasting 90 minutes or longer had an increased risk of infection
      compared to those less than 90 minutes (OR = 3.6), administration of preoperative
      antibiotics was associated with an increased risk of infection (OR = 4.6) and
      female patients were 2.6 times more likely to develop post operative infection
      than male patients.

PMID- 8575402
TI  - Causes of death in racehorses over a 2 year period.
AB  - Necropsies were performed on 496 horses that had a fatal injury or illness at a
      California racetrack during the period February 20th 1990 to March 1st 1992. The
      primary cause of death was categorised by breed, activity at time of injury or
      illness and organ system affected. Most of the submissions were Thoroughbred
      horses (432) and Quarter Horses (46). Most of the injuries occurred while racing
      (42%) and in training sessions (39%); with fewer non-exercise (12%) and accident
      (7%) related injuries or illnesses. Musculoskeletal injuries accounted for 83% of
      the Thoroughbred and 80% of the Quarter Horse submissions. The Thoroughbred
      horses incurred 306 fractures with 263 in the limbs and 90% of those in the
      forelimbs. The proximal sesamoid bone(s), third metacarpal bone and humerus were
      the most common bones fractured in Thoroughbred horses and Quarter Horses. Other
      major causes of death included respiratory, digestive and multi-organ system
      disorders.

PMID- 8575404
TI  - Density of myenteric plexuses and neurons in the large and transverse colon of
      one-day-old foals.

PMID- 8575403
TI  - Clinical efficacy and safety of clenbuterol HCl when administered to effect in
      horses with chronic obstructive pulmonary disease (COPD).
AB  - A field study of 239 horses was conducted to determine the efficacy and safety of
      clenbuterol HCl, a beta 2-adrenergic bronchodilator, when administered
      incrementally to effect in the treatment of chronic obstructive pulmonary disease
      (COPD). The severity of COPD (heaves) and response to treatment was determined by
      clinical evaluation; an overall 'heaveiness rating' (OHR) was assigned at each
      observation. The horses were treated orally b.i.d. with clenbuterol (as
      Ventipulmin Syrup), beginning with the lowest dosage of 0.8 micrograms/kg. On day
      10 of treatment at the effective dose (0.8, 1.6, 2.4 or 3.2 micrograms/kg),
      treatment was either withdrawn (Schedule A) or continued for an additional 20
      days (Schedule B). Horses on Schedule A demonstrated a significant improvement in
      the mean OHR on treatment Day 10 compared to the baseline overall heaveiness
      rating (BOHR) and a significant increase in the mean OHR (relapse) after the drug
      was withdrawn. Schedule B horses showed significant improvement (compared to
      BOHR) on treatment Days 10, 20 and 30. Incremental dosing with clenbuterol
      provided clinical improvement in 75% of the horses with a lower 95% confidence
      limit of 71%. Twenty-five percent were nonresponders. A greater percentage of the
      more severely affected horses required the 3.2 micrograms/kg dosage or were
      nonresponders compared to horses with a lower BOHR. Side effects of sweating,
      muscle tremor, and nervousness were of low intensity (mild to moderate) and
      frequency (< 7% of all observations) due to the regimen of incremental dosing to
      effect.

PMID- 8575405
TI  - Renal sodium excretion and edematous disorders.
AB  - Body sodium and water homeostasis is regulated by multifactorial renal and
      extrarenal systems. Following a description of these systems, four common edema
      states are reviewed, with special emphasis on the pathophysiologic mechanisms
      leading to sodium and water retention.

PMID- 8575406
TI  - Natriuretic hormones.
AB  - Natriuretic peptides act as endocrine and paracrine hormones to regulate
      extracellular fluid volume and blood pressure at all levels of the circulation.
      Atrial and brain natriuretic peptides, circulating hormones secreted in response
      to increased stretch within the cardiac atrium and ventricle, respectively,
      induce comparable natriuresis, vasodepression, and inhibition of aldosterone via
      the guanylate-cyclase receptor, NPR-A. C-type natriuretic peptide acts via a
      different guanylate-cyclase receptor, NPR-B, to affect vascular cell growth and
      remodeling. Possible complex interactions among all three natriuretic peptides
      are reviewed. Although the importance of natriuretic peptides is still being
      assessed, data from animal studies strongly support an important role fore these
      hormones in cardiovascular homeostasis.

PMID- 8575407
TI  - Secondary aldosteronism.
AB  - Conditions of secondary aldosteronism are common in clinical medicine, occurring
      in normotensive and hypertensive settings. In some conditions such as edema
      disorders, this represents a partially beneficial response to restore volume and
      Na at the expense of hypokalemia. In RVH and malignant hypertension, the
      aldosteronism may be beneficial, but most evidence shows a detrimental impact. In
      both situations, aldosterone does not compensate fully for Na degradation and
      facilitates K loss. In pregnancy, aldosterone's effects is more successful for
      volume conservation, and the action on K is almost completely overridden by other
      K-sparing factors. Chronic renal failure seems to best benefit from
      hyperaldosteronism, but the response is limited because aldosterone must act on
      extrarenal targets. In iatrogenic causes of secondary aldosteronism, the effects
      of aldosterone are mostly detrimental. The overall conclusion supports the
      hypothesis that aldosterone functions best in physiologic situations, but in
      pathophysiologic settings it does not perfectly compensate for the basic defect.
      This implies that in these complex conditions, successful therapy should address
      the disorder in aldosterone and also the other underlying pathophysiologic
      mechanisms.

PMID- 8575408
TI  - Idiopathic edema. Pathogenesis, clinical features, and treatment.
AB  - Idiopathic edema is usually orthostatic. It is most evident in the feet or
      abdomen after prolonged standing or sitting and in the fingers and eyelids after
      recumbency overnight. It occurs almost exclusively in post-pubertal women and is
      associated with discomfort in the areas of fluid accumulation (including symptoms
      of the carpal tunnel syndrome, nonarticular rheumatism, and headaches, sometimes
      with pseudotumor cerebri), and weight gain with excessive increments from morning
      to evening. The pathogenesis, diagnosis, and treatment of idiopathic edema are
      discussed.

PMID- 8575409
TI  - Diabetes insipidus.
AB  - Diabetes insipidus, characterized by the excretion of copious volumes of
      unconcentrated urine, results from a deficiency in the action of the antidiuretic
      hormone arginine vasopressin and can be caused by any of four fundamentally
      different defects, including impaired secretion (neurohypophyseal diabetes
      insipidus), impaired renal response (nephrogenic diabetes insipidus), excessive
      fluid intake (primary polydipsia), or increased metabolism of the hormone
      (gestational diabetes insipidus). Differentiation between their causes,
      pathophysiology, and treatment methods is essential for effective management and
      is best achieved by a combination of hormonal, clinical, and neuroradiologic
      observations. Understanding of the genetic forms has advanced greatly and may
      soon lead to improved methods of prevention, diagnosis, and treatment.

PMID- 8575410
TI  - Potassium homeostasis and hyperkalemic syndromes.
AB  - Acute hyperkalemia can be a life-threatening consequence of a variety of
      pathologic, pharmacologic, and iatrogenic disorders. Recognition and prompt
      therapy often reverse the electrophysiologic complications within minutes.
      Therefore, physicians must have a thorough understanding of potassium
      homeostasis. The causes of hyperkalemia, intracellular-to-extracellular shifts of
      potassium, excess exogenous potassium loads, and pseudohyperkalemia are
      discussed.

PMID- 8575411
TI  - Primary aldosteronism.
AB  - The mineralocorticoid-excess state caused by primary aldosteronism usually causes
      hypokalemia and moderate to sever hypotension. A directed approach to the patient
      with suspected primary aldosteronism is essential. Appropriate use of biochemical
      and diagnostic imaging studies can identify the etiology of the primary
      aldosteronism in an efficient and noninvasive way in most cases. Precision in
      defining the etiology of the mineralocorticoid-excess state logically leads to
      therapeutic strategies that usually cure or improve the hypertensive state.

PMID- 8575412
TI  - Apparent mineralocorticoid excess.
AB  - Apparent mineralocorticoid excess is a congenital syndrome of sodium retention
      and hypertension with suppressed renin and aldosterone and normal cortisol
      levels. Patients with the syndrome have, however, highly abnormal levels of
      urinary cortisol to cortisone metabolites, indicating a reduced or absent
      activity of 11 beta-hydroxysteroid dehydrogenase 2, the enzyme responsible for
      conversion of cortisol to receptor-inactive cortisone. Very recently, the gene
      for 11 beta-hydroxysteroid dehydrogenase 2 was cloned, and mutations leading to
      absent or markedly reduced enzyme activity were found in 10 or 11 patients to
      date.

PMID- 8575413
TI  - Disorders of magnesium metabolism.
AB  - Magnesium depletion is more common than previously thought. It seems to be
      especially prevalent in patients with diabetes mellitus. It is usually caused by
      losses from the kidney or gastrointestinal tract. A patient with magnesium
      depletion may present with neuromuscular symptoms, hypokalemia, hypocalcemia, or
      cardiovascular complication. Physicians should maintain a high index of suspicion
      for magnesium depletion in patients at high risk and should implement therapy
      early.

PMID- 8575414
TI  - Dietary factors and blood pressure regulation.
AB  - This article reviews the potential effects of dietary constituents and
      manipulations on blood pressure. Dietary approaches with documented efficacy are
      discussed, as are the effects of other nutritional factors, which, after study,
      demonstrate no proven change on blood pressure. The effects of dietary ions
      (micronutrients) and of individual dietary macronutrients also are reviewed. The
      article concludes by examining the evidence for effects of weight loss, alcohol
      restriction, and vegetarian diets and offers for future research.

PMID- 8575415
TI  - Analysis of in vivo mutation induced by N-ethyl-N-nitrosourea in the hprt gene of
      rat lymphocytes.
AB  - The rat lymphocyte hprt assay measures in vivo mutagenicity by quantifying the
      frequency of 6-thioguanine-resistant (TGr) spleen lymphocytes cultured in vitro.
      In this study we have examined the types of mutations induced in the hprt gene of
      TGr lymphocyte clones from female Fischer 344 rats exposed to 100 mg/kg N-ethyl-N
      nitrosourea (ENU). Hprt exons 3 and 8 were amplified from DNA extracted from each
      of 249 clones, and the resulting products were screened for mutant:wild-type
      heteroduplex formation by denaturing gradient gel electrophoresis. The analysis
      revealed 59 clones with mutations in exon 3, and 20 clones with mutations in exon
      8. DNA sequence analysis of the heteroduplexes identified 84 mutations: all of
      the mutations were base pair substitutions, and 88% were mutations of A:T base
      pairs. At least 82% were induced independently. These results suggest that the
      mutations found in TGr rat lymphocytes from ENU-treated rats were due mainly to
      ethylthymidine adducts. In addition, a comparison of these results with
      previously reported in vivo ENU mutational profiles indicates that the types of
      mutation detected by heteroduplex screening of rat hprt exons 3 and 8 are
      representative of mutation in the entire protein coding sequence.

PMID- 8575416
TI  - Mutation spectra in salmonella of chlorinated, chloraminated, or ozonated
      drinking water extracts: comparison to MX.
AB  - Drinking water samples were prepared in a pilot-scale treatment plant by
      chlorination (Cl2), chloramination (NH2Cl), ozonation (O3), or O3 followed by Cl2
      or NH2Cl; and the nonvolatile acidic organics of the raw and treated waters were
      extracted by XAD/ethyl acetate and evaluated for mutagenicity in Salmonella (
      S9). The extracts were 2-8 times more mutagenic in TA100 than in TA98, and the
      mutagenic potencies of the water extracts ranked similarly in both strains: Cl2 >
      O3 + Cl2 > NH2Cl > O3 + NH2Cl > O3 > raw. 3-Chloro-4-(dichloromethyl)-5-hydroxy
      2(5H)-furanone (MX), which was estimated to account for approximately 20% of the
      mutagenic activity of the extracts, was shown to be the most potent compound
      tested thus far in a prophage-induction assay in Escherichia coli and a forward
      mutation assay in Salmonella TM677. The mutations in approximately 2,000
      revertants of TA98 and TA100 induced by MX and the water extracts were analyzed
      by colony probe hybridization and polymerase chain reaction/DNA sequence
      analysis. The water extracts and MX produced similar mutation spectra, which
      consisted in TA100 of predominantly of GC-->TA transversions in the second
      position of the CCC (or GGG) target of the hisG46 allele. This spectrum resembles
      that produced by large aromatic compounds and is distinct from that produced by
      alkylating agents and the semivolatile drinking water mutagen dichloroacetic
      acid. In TA98, MX and those water extracts resulting from the introduction of the
      chlorine atom produced 50-70% hotspot 2-base deletions and 30-50% complex
      frameshifts (frameshifts with an adjacent base substitution--mostly GC-->TA
      transversions as found in TA100). No other compound or mixture is known to induce
      such high frequencies of complex frameshifts. These results suggest that MX and
      "MX-like" compounds (possibly halogenated aromatics, such as halogenated
      polycyclic aromatic hydrocarbons) account for much of the mutagenic activity and
      specificity of the nonvolatile organics in drinking water and that these
      halogenated organics are especially capable of promoting misincorporation by the
      DNA replication complex. This study provides further evidence that the mutation
      spectrum of a complex mixture reflects the dominance of one or a few classes of
      chemical mutagens within the mixture.

PMID- 8575417
TI  - Methylglyoxal induces hprt mutation and DNA adducts in human T-lymphocytes in
      vitro.
AB  - Methylglyoxal (MG) is a mutagen present in several foodstuffs, including coffee.
      We have used the 32P-postlabelling method to measure MG-deoxyguanosine adduct
      levels, and the T-cell cloning technique, to study the frequency of hprt
      (hypoxanthine-guanine phosphoribosyl transferase) mutant cells after treatment of
      human lymphocytes with MG in vitro. The mutant induction by single (18 hr) high
      dose (1.0-1.5 mM) treatment was comparable to that induced by repeated (3 x 48
      hr) low-dose (0.1-0.4 mM) treatment. The latter also correlated with the adduct
      levels measured in the same experiment. The relative cell survival measured by
      direct cloning after the final treatment agreed well with the growth curves
      monitored during the expression phase. Our results show that MG is capable of
      inducing hprt mutations as well as DNA adducts in human lymphocytes at doses with
      low cytotoxicity. However, significant adduct formation (two- to threefold) could
      be obtained only after the first exposure in cells subjected to a repeated
      treatment protocol, and the induced mutant frequency was low (two- to fourfold
      over background). Thus, MG seems to be a comparatively weak mutagen in this
      system.

PMID- 8575418
TI  - Indications for a threshold of chemically-induced aneuploidy in vitro in human
      lymphocytes.
AB  - The possible existence of a threshold for compounds inducing chromosomal loss was
      investigated for four known aneugens (colchicine, COL; carbendazim, MBC;
      mebendazole, MEB; nocodazole, NOC) and two clastogens (methyl methanesulfonate,
      MMS; mitomycin C, MMC) using the micronucleus (MN) test in human lymphocytes. The
      presence of a whole chromosome in the MN was studied by fluorescent in situ
      hybridization (FISH) using a synthetic pancentromeric oligonucleotide probe. FISH
      was applied on two different MN preparations: cytokinesis-blocked MN (MNCB)
      assay, and MN sorted by flow cytometry. At subtoxic concentrations analyzed by
      MNCB and FISH, COL, MEB, MBC, and NOC induced a concentration-dependent increase
      in centromere-positive MN (MNCen+). MMC seemed to induce an increase in both
      types of MN (MNCen- and MNCen+), while MMS induced only MNCen-. On the sorted
      micronuclei (in a wide range of low to subtoxic concentrations), the
      concentration-effect profile for MNCen+, with the four aneugens tested, showed a
      statistically nonsignificant increase over a range of concentrations, followed by
      a second range of high concentrations with a statistically significant increase.
      To analyze the existence of a threshold, a piecewise linear regression was
      applied to the data. The first concentration that showed a statistically
      significant increase in MNCen+ was chosen as a breakpoint (0.037 microM for COL,
      2.62 microM for MBC, 0.27 microM for MEB, and 0.066 microM for NOC). The
      statistical correlation between observed and predicted values showed a high
      correlation (r = 0.99), indicating a clear threshold for aneuploidy induction.
      However, for MMS the concentration-effect profile for MNCen+ showed a continuous
      concentration-dependent decrease with no threshold. With the two cytotoxicity
      assays used (Bio-Rad and MTT), no significant reduction was detected either in
      the protein content or in mitochondrial succinate dehydrogenase activity with all
      chemicals tested for MN induction. Therefore, our data suggest that the observed
      thresholds were not due to indirect toxic effects but to real aneugenic effects.

PMID- 8575419
TI  - An investigation of the DNA-damaging ability of benzene and its metabolites in
      human lymphocytes, using the comet assay.
AB  - Benzene and five of its known metabolites--muconic acid, hydroquinone, catechol,
      p-benzoquinone, and benzentriol--were examined for DNA damage in human
      lymphocytes using the alkaline Comet assay, and conditions were optimised to
      determine responses. Metabolic activation (S-9 mix) was included in the assay for
      varying times to try to enhance effects. In addition, the effects of catalase
      were investigated as it is known to be present in S-9 mix reducing oxidative
      damage, and some benzene metabolites are known to react through oxygen radical
      mechanisms. Effects were also examined in cycling cells to determine whether they
      were more sensitive to damage then noncycling cells. Comets were measured either
      by eye or by image analysis. Data have been presented according to length of
      treatments. When Comets were measured by eye after treatment with hydrogen
      peroxide (H2O2), the positive control, and each compound for 0.5 hr, only H2O2
      and benzenetriol induced pronounced DNA damage without metabolic activation. The
      effect of catechol was moderate compared with that of benzenetriol. There was a
      very weak effect of benzene in the absence of rat liver S-9 mix. In the presence
      of S-9 mix, benzene was not activated. The effect of benzenetriol was greatly
      reduced by the external metabolising system, but p-benzoquinone became activated
      to some extent. Catalase abolished the effect of benzenetriol, suggesting that
      H2O2 formed during autoxidation may be responsible for the DNA-damaging ability
      of this metabolite. The presence of catalase in S-9 mix may explain the
      detoxification of benzenetriol and the failure to detect consistent benzene
      responses. Mitogen-stimulated cycling cells were less sensitive to H2O2 and
      benzenetriol than unstimulated G0 lymphocytes. When comets were measured by image
      analysis, a 0.5-hr treatment with H2O2 and benzenetriol and catechol confirmed
      results analysed by eye, with S-9 mix greatly reducing responses. When treatments
      were increased to 1 hr in the presence and absence of S-9 mix, benzene at a 5
      fold increased dose produced a significant positive response but not at the lower
      dose. When treatment times were increased to 2 and 4 hr, doses were also
      increased, and muconic acid, hydroquinone, catechol, and benzoquinone in the
      presence of S-9 mix showed positive time and dose-related responses, and at the
      highest dose of benzoquinone the morphology of the nucleus was affected. Effects
      tended to become more pronounced at high doses and after longer exposures,
      although this was not always consistent from experiment to experiment. In
      conclusion, benzene and all metabolites investigated gave positive responses.
      Where altered responses were observed, they were significantly different from the
      corresponding controls.

PMID- 8575420
TI  - Induction of micronuclei in human sperm-hamster egg hybrids at the two-cell stage
      after in vitro gamma-irradiation of human spermatozoa.
AB  - The efficiency of the micronucleus test to assess radiation-induced chromosomal
      damage in human spermatozoa has been investigated. Micronuclei were scored in
      human sperm-hamster egg hybrids at the two-cell stage, after exposure of human
      spermatozoa to in vitro gamma-rays at doses of 0.00, 0.10, 0.25, 0.50, 1.00,
      2.00, and 4.00 Gy. The relationship between the yield of micronuclei per two-cell
      stage as well as the percentage of two-cell stages with micronuclei and the
      different doses of irradiation were fitted to linear equations. To evaluate
      whether scoring micronuclei is useful for the quantification of chromosomal
      damage occurring in human spermatozoa, induced micronuclei at the different doses
      of sperm irradiation were compared to the induction of breaks and fragments in
      sperm-derived chromosomes. After interspecific fertilization of zona-free hamster
      oocytes by irradiated spermatozoa, a total of 699 fertilized eggs at the two-cell
      stage and a total of 387 sperm-derived complements were analyzed. The incidence
      of fertilized eggs with micronuclei at the two-cell stage coincided well with the
      incidence of sperm-derived chromosome breaks and fragments (e.g., 8.9% vs. 6.7%
      in the 0.25 Gy group and 52.8% vs. 58.6% in the 4.00 Gy group). A similar
      correlation was found between the number of micronuclei per two-cell stage and
      the number of breaks and fragments per sperm complement (0.09 vs. 0.07 in the
      0.25 Gy group and 0.71 vs. 0.81 in the 4.00 Gy group). The results show that this
      test system can be used for the quantification of spontaneous or induced
      chromosomal damage in human spermatozoa.

PMID- 8575422
TI  - Enhancement of SCE frequency by alpha-naphthoflavone in cultured lymphocytes in
      relation to environmental factors.
AB  - One hundred and nine healthy subjects living in an urban area of Tuscany were
      monitored using sister chromatid exchange (SCE) analysis on lymphocytes cultured
      in standard or alpha-naphthoflavone (ANF)-supplemented medium in order to collect
      the most complete data possible for those constitutional and environmental
      factors with which genotoxic risk can be associated. ANF genotoxicity depends on
      its metabolic activation by cellular P-450 monooxygenase systems whose activity
      can be modulated by exposure to carcinogenic but nongenotoxic xenobiotics.
      Lymphocytes grown in standard conditions showed a significant increase of SCE
      frequency associated with smoking habits and age. Although the addition of ANF
      caused an upward shift of SCE frequency in all subjects, smokers, coffee
      drinkers, and blue-collar workers showed a significantly higher SCE level; this
      suggests that potential risk factors rising from a modified cell metabolism are
      present in these categories. These results indicate that in vitro ANF treatment
      of lymphocytes could be a useful tool in the detection of environmental exposure
      to those classes of chemicals involved in metabolic activation of promutagens.

PMID- 8575421
TI  - Sister chromatid exchange in human lymphocytes induced by propoxur following
      plant activation by Vicia faba.
AB  - Because the carbamate insecticide propoxur induced sister chromatid exchanges
      (SCE) in Vicia faba but was ineffective in producing SCE in lymphocytes in
      culture, it was hardly suspected that plant metabolism was involved. Experiments
      were conducted in which metabolic activation was afforded by Vicia faba roots,
      and SCE in human lymphocytes in vitro was used to assess cytogenetic damage.
      Several concentrations of propoxur (250, 500, 1,000, 1,500, and 2,000 ppm) were
      applied for 4 hr to the roots of Vicia faba. Extracts prepared from these
      treatments were added to the lymphocyte cultures and a significant increase of
      SCE frequencies with a concentration-response relationship could be detected. The
      lymphocyte proliferation kinetics and the proliferation rate index (PRI) were not
      affected (except in the highest concentration, of 2,000 ppm). This general
      behavior was in agreement with the presence of an enzymatic system (S10 fraction)
      in Vicia roots capable of metabolizing or activating the propoxur. With 2,000
      ppm, cell necrosis was produced in Vicia; therefore, this extract did not induce
      SCE in lymphocytes. However, lymphocyte proliferation kinetics were delayed and
      PRI was significantly decreased. Ethanol, a promutagen activated by this plant,
      was applied directly to the lymphocyte cultures as a positive control, and the
      response was negative. On the other hand, the extracts of roots treated with
      ethanol increased the SCE to more than twice that of the negative control, but
      the lymphocyte proliferation kinetics and PRI were not affected.

PMID- 8575423
TI  - Genotoxicity of the natural cercaricides "sucupira" oil and eremanthine in
      mammalian cells in vitro and in vivo.
AB  - "Sucupira" oil and the lactone eremanthine, extracted from Pterodon pubescens and
      Eremanthus elaeagnus, respectively, are known for their cercaricidal action in
      experimental animals. Because of their biological effect, they have the potential
      to be used for the prophylaxis of schistosomiasis caused by Schistosoma mansoni.
      To test the clastogenicity of these agents, "sucupira" oil, either pure or
      diluted in corn oil, was tested in vivo on Wistar rat bone marrow cells following
      dermal application. Metaphase analysis showed that the compound did not induce a
      significant increase in the frequencies of chromosomal aberrations. When
      eremanthine was tested on BALB/c mice following gavage at doses of 100, 200, and
      300 mg/kg bw, it did not induce structural or numerical chromosomal aberrations.
      In the in vitro treatment of human lymphocyte cultures, eremanthine also did not
      cause any increase in chromosomal aberrations or sister chromatid exchanges at
      the following concentrations in culture medium: 1.25, 2.50, and 5.00
      micrograms/ml. From these results, under our experimental conditions, neither
      "sucupira" oil nor eremanthine showed clastogenic effects on mammalian cells in
      vivo or in vitro.

PMID- 8575424
TI  - Alkaline single cell gel (comet) assay and genotoxicity monitoring using
      bullheads and carp.
AB  - Monitoring genotoxicity of the environment using endemic organisms as sentinels
      requires the development of sensitive assays. Toward this end, we explored the
      feasibility of applying the alkaline single cell gel (SCG) or "comet" assay. This
      approach involves detection, under alkaline conditions, of cell DNA fragments
      which, on electrophoresis, migrate from the nuclear core, resulting in a "comet
      with tail" formation. Tail length has been correlated with level of genotoxicant
      exposure in a number of organisms. The fish used in this study were benthic
      feeding bullheads (Ameiurus nebulosus) and carp (Cyprinus carpio). On
      electrophoresis of erythrocyte DNA under alkaline conditions, we found a linear
      increase in the tail length/core width ratio over a broad range of
      cyclophosphamide doses. Freshly caught bullheads from seven different sites
      showed a wide range of DNA damage. Bullheads from Big Creek (western Lake Erie),
      Hamilton Harbour (western Lake Ontario), and the Detroit River gave ratios of
      3.81 to 4.65. Based on polycyclic aromatic hydrocarbon (PAH) and polychlorinated
      biphenyl (PCB) levels, the sediment at these three sites is considered to be
      heavily polluted. Bullheads from southern Lake Huron, which is relatively clean,
      and from a fish hatchery in Brockport, New York, gave ratios between 1.30 and
      1.40. Bullheads from Big Creek, maintained in the laboratory for 3 months, gave
      ratios which approached those seen in hatchery-bred fish. Results for carp were
      similar. Carp from Big Creek gave ratios of about 4.50, while carp from Lake
      Huron and laboratory-maintained carp gave values of 1.23 and 1.36, respectively.
      The results of the SCG procedure in bullheads and carp indicate that this assay
      is extremely sensitive and should be useful in detecting DNA damage caused by
      environmental contaminants.

PMID- 8575425
TI  - DNA-binding surface of RecA protein photochemical cross-linking of the first DNA
      binding site on RecA filament.
AB  - The first DNA-binding site (site I) of RecA protein on the filament has been
      mapped. RecA protein was covalently cross-linked with a 55-base synthetic single
      stranded DNA which was a good substrate for the RecA-mediated strand exchange
      reaction. The cross-linking sites of protein were determined in the regions
      spanning RecA residues 64-68, 89-106, 178-183, 199-216 and 257-280. The cross
      linking in the residues 64-68, 89-106, 199-216 and 257-280 would be due to the
      cross-linking of Tyr65, Tyr103, disordered loop 2, and Tyr264, respectively.
      These regions form a DNA-binding surface centered around the beta-sheet spanning
      residues 243-257. In the P6(1) crystal filament, the DNA-binding surface is near
      the RecA-RecA interface but are not in the filament axis. The data implicate a
      mechanism whereby the DNA binding surface would be led into the filament axis by
      a conformational change from inactive filament as the P6(1) structure to active
      filament as the RecA-DNA-ATP complex.

PMID- 8575426
TI  - Synthesis and characterization of a homogeneous chemical conjugate between basic
      fibroblast growth factor and saporin.
AB  - Basic fibroblast growth factor (FGF-2) and saporin were chemically conjugated
      using the crosslinker, N-succinimidyl-3(2-pyridyldithio)-propionate. When
      purified, the conjugate was found to be heterogeneous as analyzed by SDS/PAGE,
      size-exclusion HPLC and reverse-phase HPLC. Therefore, we sought to synthesize a
      molecule that would be homogeneous and thus easier to characterize and evaluate
      its efficacy and toxicity for pharmaceutical drug development. A homogeneous
      chemical conjugate was successfully synthesized by using a mutant FGF-2 with
      Cys96 replaced by Ser ([S96]FGF-2) and a recombinant saporin mutant containing a
      single Cys at the -1 position (C-SAP). The latter was expressed in Escherichia
      coli and isolated to 99% purity by expanded-bed adsorption chromatography
      followed by cation-exchange chromatography. The cysteine in C-SAP was activated
      by Ellman's reagent and then reacted with the only available cysteine (position
      78) in [S96]FGF-2 to produce the homogeneous conjugate, designated as FGF2-C-SAP.
      The purified FGF2-C-SAP was more than 98% pure as judged by HPLC. In vitro
      biological assays indicated that FGF2-C-SAP was a potent inhibitor of protein
      synthesis in a cell-free system and was cytotoxic to FGF-receptor-bearing cells.

PMID- 8575427
TI  - Activated alpha 2-macroglobulin promotes mitogenesis in rat vascular smooth
      muscle cells by a mechanism that is independent of growth-factor-carrier
      activity.
AB  - Vascular smooth muscle cell (vSMC) proliferation is important in atherosclerosis.
      We previously demonstrated that methylamine-activated alpha 2-macroglobulin
      (alpha 2M) and transforming growth factor beta 1 (TGF-beta 1) cause a synergistic
      proliferative response in quiescent rat aortic vSMCs [Stouffer, G. A., La-Marre,
      J., Gonias, S. L. & Owens, G. K. (1993) J. Biol. Chem. 268, 18,340-18,344]. The
      first goal of this study was to determine whether the synergy is due to the
      ability of alpha 2M-methylamine (alpha 2M-MeNH2) to bind TGF-beta 1 and target
      the growth factor to vSMCs that express the alpha 2M receptor. Receptor
      recognized alpha 2M derivatives without TGF-beta 1-binding activity, including
      ternary alpha 2M-trypsin, an 18-kDa proteolytic fragment of the alpha 2M subunit,
      and the corresponding recombinant receptor-binding fragment (rRBF) increased vSMC
      [3H]thymidine incorporation and cell number in a manner similar to alpha 2M
      MeNH2. In combination with TGF-beta 1, each alpha 2M derivative caused a
      synergistic vSMC proliferative response. vSMCs responded comparably when treated
      with alpha 2M-MeNH2 and TGF-beta 1 simultaneously or in sequence. Furthermore,
      alpha 2M-MeNH2-TGF-beta 1 complexes increased [3H]thymidine incorporation no more
      than alpha 2M-MeNH2 alone. These results indicate that TGF-beta 1 binding to
      alpha 2M is not responsible for the synergistic mitogenic activity. Additional
      studies were undertaken to determine whether activated alpha 2M independently
      induces a signal-transduction response in vSMCs. alpha 2M-MeNH2 and rRBF caused a
      rapid, transient increase in vSMC inositol 1,4,5-trisphosphate. This response was
      pertussis-toxin insensitive. Receptor-associated protein (RAP; 170 nmol/L)
      inhibited 91-95% of the specific binding of 125I-alpha 2M-MeNH2 and 125I-rRBF to
      vSMC; however, RAP did not affect the inositol 1,4,5-trisphosphate response or
      the mitogenic response. These studies suggest that vSMCs express a receptor,
      other than low-density-lipoprotein-receptor-related protein, that transduces a
      signal in response to activated alpha 2M. This receptor may mediate the mitogenic
      activity of alpha 2M in vSMC culture.

PMID- 8575428
TI  - Identification of spinach farnesyl protein transferase. Dithiothreitol as an
      acceptor in vitro.
AB  - Spinach seedlings were found to contain farnesyl protein transferase. The enzyme
      is activated by Zn2+, but not by Mg2+. The pH optimum is approximately 7.0 and
      maximal activity is obtained at 40-45 degrees C. The apparent Km for the farnesyl
      diphosphate substrate is 7 microM. Western blotting of soluble proteins with an
      antiserum raised against mammalian farnesyl protein transferase demonstrated a
      specific cross-reactivity with the spinach enzyme. The antiserum preferentially
      recognises the beta-subunit of the heterodimeric farnesyl protein transferase,
      and the corresponding spinach polypeptide has a molecular mass of 42 kDa on
      SDS/PAGE. The enzyme can employ dithiothreitol as an acceptor for the farnesyl
      moiety and catalyses the formation of a thioether linkage between these
      substrates. On the basis of this discovery, a new method was developed utilising
      the hydrophobicity of the reaction product, and its interaction with
      poly(propylene). During in vivo labelling, the plants took up dithiothreitol,
      which inhibited the incorporation of [3H]mevalonate metabolites into proteins,
      indicating that dithiothreitol might be isoprenylated in vivo as well as in
      vitro. However, isoprenylation of some proteins remains unaffected by
      dithiothreitol suggesting the existence of different isoprenylation mechanisms.
      Thus, it is demonstrated that plants possess farnesyl protein transferase, which
      resembles its mammalian and yeast homologues.

PMID- 8575429
TI  - Osmo-expression and fast two-step purification of Escherichia coli translation
      termination factor RF-3.
AB  - The gene for the translation termination factor RF-3 in Escherichia coli has
      recently been cloned and sequenced. Only small amounts of the protein have been
      purified until now, not sufficient for detailed investigation of the structure
      and function of this factor. For such studies, we have developed an
      overexpression system and a purification procedure suitable for large quantities
      of RF-3. The gene prfC was cloned into the osmo-inducible plasmid pOSEX3 and
      subsequently transformed into the E. coli strain MKH13. The expression of prfC in
      this plasmid, which is under the control of the osmotic pressure in the growth
      medium, leads to a level of RF-3 more than 100-times higher than that in wild
      type cells. Using a new two-step FPLC protein purification procedure consisting
      of ion-exchange chromatography on Q-Sepharose FF and S-Sepharose HP, we obtain
      220 mg pure RF-3 from 10 g overproducing cells, corresponding to 55 mg RF-3/l
      medium. The identity of the purified protein was confirmed by matrix-assisted
      laser desorption/ionisation mass spectrometry of tryptolytic fragments and by N
      terminal amino acid sequencing. The activity of the purified factor was tested in
      vitro by measuring the stimulation of RF-2 dependent formylmethionine release
      from a ribosomal termination complex and the binding capacity of GTP and GDP. All
      assays showed that the purified RF-3 was highly active with a specific activity
      of approximately 2000 units/mg.

PMID- 8575430
TI  - Comparison of the allatostatin neuropeptide precursors in the distantly related
      cockroaches Periplaneta americana and Diploptera punctata.
AB  - Allatostatins are a family of insect neuropeptides that inhibit juvenile hormone
      biosynthesis by the corpora allata. We have characterized cDNA and genomic DNA
      sequences that specify a preproallatostatin precursor in the oviparous cockroach
      Periplaneta americana. Comparison of this precursor with that previously
      described [Donly, B. C., Ding, Q., Tobe, S. S. & Bendena, W. G. (1993) Proc. Natl
      Acad. Sci. USA 90, 8807-8811] for the viviparous cockroach Diploptera punctata
      revealed several common features. First, the precursors are remarkably similar in
      size and the organization of the peptides within the precursor is conserved. The
      separation of the peptides into groups by acidic domains within the precursor has
      been maintained. The P. americana precursor contains 14 allatostatin-like
      peptides that contain the core C-terminal sequence (Tyr/Phe)-Xaa-Phe-Gly
      (Leu/Ile)-NH2, as compared to the D. punctata precursor, which contains 13. Five
      of the peptides are perfectly conserved between the two species. The remainder,
      with one exception, contain amino acid substitutions in the N-terminal address
      portion of the peptide. Several features of expression are also similar between
      these two species. In both, a single copy gene specifies a large allatostatin
      transcript of 5.0 kb in P. americana and 9.2 kb in D. punctata. In P. americana,
      allatostatin transcripts appear to be produced by numerous cells in different
      regions of the brain.

PMID- 8575431
TI  - Solution conformation of the Pseudomonas syringae pv. syringae phytotoxic
      lipodepsipeptide syringopeptin 25-A. Two-dimensional NMR, distance geometry and
      molecular dynamics.
AB  - Syringopeptin 25-A is a phytotoxic amphiphilic lipodepsipeptide containing 25
      amino acid residues, produced by some isolates of the plant pathogenic bacterium
      Pseudomonas syringae pv. syringae. Previous papers have reported its covalent
      structure and some of its biological properties. Attention has now been directed
      to define its conformation in solution, a structural feature regarded as
      important for understanding its possible role in the bacterial colonization of
      host plants, and its toxic action on the plant cell. Here we report the
      stereochemistry of its amino acid components, the complete interpretation of the
      two-dimensional NMR spectra and NOE data, and finally the structure obtained by
      computer simulations applying distance geometry and molecular dynamics
      procedures. The conformation of syringopeptin 25-A in aqueous solution includes
      three different structural regions interrupted by rigid 2,3-dehydro-2
      aminobutyric acid residues: a loop from residue 2 to 6, a helicoidal zone from 8
      to 15, and the lactone ring from 18 to 25. The three-dimensional structure of the
      lactone moiety is very similar to that of two previously studied bioactive
      lipodepsinonapeptides. Preliminary circular dichroism evidence of conformational
      variations in solution of trifluoroethanol, which stimulates a membrane-like
      environment, are also reported.

PMID- 8575432
TI  - Monoclonal antibodies specific for natural human neutrophil gelatinase B used for
      affinity purification, quantitation by two-site ELISA and inhibition of enzymatic
      activity.
AB  - Human gelatinase B was produced from peripheral blood neutrophils and purified by
      affinity chromatography on gelatin sepharose. This material was used as an
      antigen to prepare mouse monoclonal antibodies (mAb). The resulting hybridomas
      were selected on the basis of binding to biotinylated antigen and by a sandwich
      ELISA using gelatinase-B-specific polyclonal rabbit antiserum and pure natural
      antigen. Five of these mAb were selected for further characterization. They all
      displayed variable epitope specificity, binding capacity and inhibitory activity.
      Whereas mAb REGA-2D9 and REGA-3G12 showed the strongest binding to biotinylated
      gelatinase B and natural gelatinase B, respectively, mAb REGA-2F9 did not bind
      biotinylated antigen. None of the mAb displayed cross-reactivity to gelatinase A
      in a direct ELISA. The mAb REGA-1G8 was found to cross-react with human serum
      albumin. The binding capacity of the other four mAb with leukocyte gelatinase B
      was compared and a sensitive sandwich ELISA was developed with the antibodies
      REGA-3G12 and REGA-2D9 (detection limit 0.5 ng/ml). The mAb REGA-3G12 was unique
      in that it inhibited catalysis by gelatinase B. This was shown by assaying the
      degradation of nasal septum type II gelatin in the presence and absence of each
      of the five mAb. Furthermore, mAb REGA-3G12 inhibited the degradation of
      biotinylated gelatin in a microtiterplate solution assay. In addition to the
      potential use of the inhibitory mAb REGA-3G12 in the treatment of diseases with
      excessive gelatinase B production, several of the described mAb are useful as
      diagnostic probes to detect gelatinase B in body fluids and tissue samples of
      patients with multiple sclerosis, rheumatoid arthritis and cancer.

PMID- 8575434
TI  - Amino acid residues 721-729 are required for full factor VIII activity.
AB  - Recombinant two-chain factor VIII, from which the B domain had been deleted, was
      expressed in Chinese hamster ovary cells. In addition to the major product, three
      minor factor VIII forms were isolated. The A2 domains generated by thrombin
      cleavage showed different electrophoretic mobilities. Peptide mapping of the A2
      domains showed that two of the factor VIII forms had the expected C-terminus of
      the heavy chain at Arg740 [FVIII-(1-740)] and that the other factor VIII forms
      had C-termini at Tyr729 [FVIII-(1-729)] or Glu720 [FVIII-(1-720)]. The major
      FVIII-(1-740) form, FVIII-(1-729), and FVIII-(1-720) contained sulfated tyrosine
      residues at Tyr718, Tyr719 and Tyr723. The minor FVIII-(1-740) form was shown to
      lack sulfation at these positions. The specific clotting activity was
      approximately 1 x 10(4) U/mg for FVIII-(1-740) (both forms) and FVIII-(1-729),
      but twofold lower for FVIII-(1-720). A time study of thrombin activation showed
      that FVIII-(1-720) was activated slower than FVIII-(1-740), FVIII-(1-729) and
      plasma-derived factor VIII. Partially sulfated FVIII-(1-740) was activated at the
      same rate as the fully sulfated FVIII-(1-740). The equilibrium dissociation
      constant for binding of factor VIII to inactivated immobilized thrombin was the
      same for all factor VIII forms, showing that the slower activation of FVIII-(1
      720) was not due to a lower affinity for the anion-binding exosite in thrombin.

PMID- 8575435
TI  - Effect of inhibitors on the coordination geometries of cadmium at the metal sites
      in angiotensin-I-converting enzyme.
AB  - Perturbed angular correlation of gamma-rays (PAC) spectroscopy has been used to
      investigate the angiotensin-I-converting enzyme (ACE) of rabbit lung. By
      substituting the zinc ions in ACE with excited 111mCd2+ ions, analysis of PAC
      spectra gave directly the percentage of cadmium ions bound to ACE. The result of
      the analysis was a dissociation constant of about 1 microM for the cadmium-ACE
      complex, and a stoichiometry of two moles cadmium/mole enzyme. Cadmium binding is
      thus about two orders of magnitude weaker than zinc binding to ACE but two orders
      of magnitude stronger than cobalt binding. PAC spectra monitor the nuclear
      quadrupole interaction (NQI) for 111mCd. The NQI for ACE exhibits very low
      frequencies in the PAC spectra with a rather large spectral broadening. In the
      presence of the inhibitor ramiprilat, the frequencies increase but the spectral
      broadening is about the same as for ACE without inhibitor. When the inhibitor
      captopril is added, very high frequencies are obtained consistent with sulfur
      binding, but now with a narrower distribution of NQI's. A simple molecular
      orbital analysis of the obtained NQI's has been performed, using a coordination
      sphere of two His, one Glu residue and a solvent ligand, equivalent to the zinc
      ligands in thermolysin and carboxypeptidase. The calculated spectral parameters
      could be modelled with the measured parameters if the solvent ligand is H2O in
      free ACE, carboxylate from ramiprilat in the ACE-ramiprilat complex and a
      mercapto group in the ACE-captopril complex. The coordination geometry for
      cadmium carboxypeptidase obtained by X-ray diffraction gives a calculated set of
      NQI parameters consistent with the measured parameters for cadmium in the
      captopril-ACE complex using a mercapto group as the solvent ligand. However, for
      ACE and its complex with ramiprilat, a significant distortion of the cadmium
      geometry for carboxypeptidase A had to be adopted in order to calculate NQI's
      close to the experimental values.

PMID- 8575433
TI  - Kinetic studies of a soluble alpha beta complex of nitrate reductase A from
      Escherichia coli. Use of various alpha beta mutants with altered beta subunits.
AB  - A soluble alpha beta complex of nitrate reductase can be obtained from a strain
      of Escherichia coli that lacks the narI gene and expresses only the alpha and
      beta subunits. The beta subunit contains four Fe-S centres and the alpha subunit
      contains the molybdenum cofactor, which is the site at which nitrate is reduced.
      Despite the lack of the gamma subunit of the complete enzyme, this complex can
      still catalyse the reduction of nitrate with artificial electron donors such as
      benzyl viologen, so that it is suitable for studying the transfer of electrons
      between these two types of redox centre. To examine whether the electrons from
      reduced benzyl viologen are initially delivered to the Fe-S centres, or directly
      to the molybdenum cofactor, or both, we have studied the steady-state kinetics
      and the binding of benzyl viologen to the alpha beta complex and mutants alpha
      beta* with altered beta subunits. Reduction of the enzyme by reduced benzyl
      viologen in the absence of nitrate showed that all four Fe-S centres and the
      molybdenum cofactor could be reduced. Two classes of site with different
      equilibrium constants could be distinguished. The kinetic results suggest that
      benzyl viologen supplies its electrons directly to the molybdenum cofactor, at a
      rate showing a hyperbolic dependence on the square of the concentration of the
      electron donor. A reaction mechanism is proposed for the reduction of nitrate
      catalysed by the alpha beta complex of nitrate reductase with artificial electron
      donors.

PMID- 8575436
TI  - Isolation and structural characterization of N-acetyl- and N-glycolylneuraminic
      acid-containing GalNAc-GD1a isomers, IV4GalNAcIV3Neu5AcII3Neu5GcGgOse4Cer and
      IV4GalNAcIV3Neu5GcII3Neu5AcGgOse4Cer, from bovine brain.
AB  - A ganglioside preparation containing two structurally related minor gangliosides
      (Gg 1 + 2) was isolated from bovine brain ganglioside mixture and characterized.
      Treatment of 50 g ganglioside mixture with Clostridium perfrigens sialidase,
      followed by chromatography on DEAE-Sepharose and silica gel columns, yielded 20
      mg Gg 1 + 2. By chemical analyses, 1H- and 13C-NMR spectroscopy, enzymic
      hydrolyses using human beta-hexosaminidase A and clostridial sialidase, and TLC
      overlay with the conjugated cholera toxin B subunit, the two novel gangliosides
      Gg 1 and Gg 2 were identified to be: Gg 1, GalNAc-GD1a(Neu5Ac/Neu5Gc), beta
      GalNAc-(1-4)-[alpha-Neu5Ac-(2-3)]-beta- Gal-(1-3)-beta-GalNAc-(1-4)-[alpha-Neu5Gc
      (2-3)]-beta-Gal-(1-4)-be ta- Glc-(1-1)-Cer; Gg 2, GalNAc-GD1a(Neu5Gc/Neu5Ac),
      beta-GalNAc-(1-4)-[alpha-Neu5Gc-(2-3)]- beta-Gal-(1-3)-beta-GalNAc-(1-4)-[alpha
      Neu5Ac-(2-3)]-beta-Gal-(1- 4)-beta- Glc-(1-1)-Cer. These two gangliosides contain
      the identical pentasaccharide backbone except that the substitution of the two
      sialic acids, Neu5Ac and Neu5Gc, are in the reversed position of the external and
      the internal Gal residues. Our analyses showed that the content of Gg 1 and Gg 2
      were approximately 0.12% and 0.08%, respectively, of the total brain ganglioside
      mixture.

PMID- 8575437
TI  - Phylogenetic conservation of 4-aminobutyric acid (GABA) transporter isoforms.
      Cloning and pharmacological characterization of a GABA/beta-alanine transporter
      from Torpedo.
AB  - A family of structurally related, Na+/Cl(-)-dependent plasma-membrane
      transporters catalyze the uptake of several neurotransmitters, osmolytes and
      other metabolites into cells. Four different members of this transporter family
      have been cloned from mammalian sources which all transport 4-aminobutyric acid
      (GABA) but differ in their pharmacological profiles and in their tissue
      distribution. We report on the cloning, sequencing and functional expression of a
      transporter for GABA and beta-alanine from the electric lobe of Torpedo.
      According to similarity of amino acid sequence (77% identity), pharmacological
      properties, and tissue distribution (nervous-system-specific), it appears to be
      the counterpart of the beta-alanine-sensitive GABA transporter, GAT-B/GAT-3/GAT4,
      previously cloned from rat and mouse. The identification of another GABA
      transporter isoform from Torpedo (after the recent characterization of a Torpedo
      GAT-1 transporter) indicates that GABA-transporter isoforms are phylogenetically
      ancient and arose before the divergence of vertebrates. Sequence comparison
      between isofunctional transporters from evolutionarily distant species aids in
      the identification of amino acid residues that are critical for functional
      specificity. The expression of transporters for GABA and beta-alanine raises
      questions regarding the unidentified physiological role of these amino acids in
      Torpedo electric lobe.

PMID- 8575438
TI  - Modulation of the platelet-derived-growth-factor-induced calcium signal by
      extracellular/intracellular pH in Syrian hamster embryo cells. Implications for
      the role of calcium in mitogenic signalling.
AB  - Studies have been performed to understand the interactions and the role which
      intracellular calcium and intracellular pH have in mediating mitogen-stimulated
      cellular proliferation. Stimulation of Syrian hamster embryo (SHE) cells with the
      mitogen platelet-derived growth factor A/B (PDGF) results in intracellular
      acidification and capacitative calcium entry involving the intracellular release
      of calcium via the inositol trisphosphate gamma receptor calcium channel,
      followed by an extracellular influx of calcium through a dihydropyridine
      sensitive plasma membrane calcium channel. Chronic extracellular/intracellular
      acidification results in the inactivation of both these calcium channels due to
      slowly reversible protein alterations. Paradoxically, transient intracellular
      acidification, like that following PDGF stimulation, could not stimulate the
      activation of either calcium channel. In addition, even though intracellular
      calcium fluxes by themselves could intiate intracellular acidification, loss of
      the PDGF-induced calcium signal did not result in the loss of the PDGF-induced
      transient intracellular acidification. Importantly with regard to the role
      intracellular calcium and pH have in mediating the mitogenic signal leading to
      cellular proliferation, chronic extracellular/intracellular acidification, which
      leads to a complete loss of the PDGF-induced calcium signal, did not result in
      the loss of PDGF-induced mitogenesis. These results indicate that the PDGF
      induced calcium signal is not essential for PDGF-stimulated mitogenesis in Syrian
      hamster embryo cells. In contrast, blocking the PDGF-induced transient
      intracellular acidification completely blocks PDGF-induced mitogenesis,
      indicating that the mitogen-induced transient intracellular acidification, unlike
      the intracellular calcium ion signal, is indispensible for cellular proliferation
      in Syrian hamster embryo cells.

PMID- 8575439
TI  - Expression and characterization of the reverse transcriptase enzyme from type 1
      human immunodeficiency virus using different baculoviral vector systems.
AB  - To produce the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase
      (RT) in amounts required to study its structure and function, the p66 enzyme
      subunit was expressed using two different baculovirus vectors in Sf158 insect
      host cells. Both vectors permitted an efficient HIV-1 RT expression. The
      resulting products were purified up to 90% homogeneity, characterized, and
      investigated for their susceptibility to digestion with various proteases. The
      recombinant baculoviral RT obtained with the pAc373 expression vector was
      purified as a p66/p60 heterodimer. The recombinant His-RT was expressed with the
      pBlueBacHis vector. Thereby, the protein was tagged with an N-terminal
      hexahistidine peptide and it was purified as a p70/p70 homodimer. The two enzymes
      differed in their specific activity, kinetic properties, and in vitro activation
      by viral and non-viral proteases. The recombinant His-RT exhibited a lower
      specific activity than the recombinant RT. The latter yielded enzyme activities
      as high as an Escherichia coli-expressed RT. Removal of the hexahistidine tag
      from the recombinant His-RT by digestion with enterokinase resulted in a complete
      loss of enzyme activity. Thus, the hexahistidine tag might be an intrinsic part
      of the active recombinant His-RT.

PMID- 8575440
TI  - Mouse preproendothelin-1 gene. cDNA cloning, sequence analysis and determination
      of sites of expression during embryonic development.
AB  - Endothelin-1 (ET-1) is a peptide implicated in a wide variety of functions
      involving vascular and non-vascular systems. We have cloned the cDNA encoding the
      mouse prepro-endothelin-1 (PPET-1) and determined its nucleotide sequence. The
      putative PPET-1 peptide processing sites are all conserved and the deduced 21
      amino-acid mature ET-1 peptide is identical to that of the rat, human, bovine,
      porcine and rabbit. Using the cloned cDNA as a probe for in situ hybridization,
      we detected PPET-1 mRNA in different tissues at different stages of mouse
      embryonic development. Embryos at a stage as early as 9.5 days postcoitum (E9.5)
      have very strong expression in the branchial epithelium, optic vesicle and the
      endothelial cells of large blood vessels, including the dorsal aorta and aortic
      arches. While the expression level in the branchial epithelium was decreasing
      towards the later stage of embryogenesis, the expression in the endothelial cells
      increased with age. At E10.5, PPET-1 mRNA was also detected in the otic vesicle
      as well as in the developing gut epithelium. At later stage of development, the
      expression of PPET-1 was primarily found in the vascular endothelial cells,
      cochlea, eye and the gut, with the highest level of PPET-1 mRNA in the
      endothelial cells of the lung. These data will be useful for analyzing the
      function of ET-1 in these organs.

PMID- 8575441
TI  - Protein p53 modulates transcription from a promoter containing its binding site
      in a concentration-dependent manner.
AB  - Tumor suppressor protein p53 binds to DNA in a sequence-specific manner and
      activates transcription from promoters near its binding site. It is also known to
      repress promoters lacking the p53-binding site. In this study, we demonstrate
      that p53 can act as a transcriptional activator or repressor in vivo using the
      same reporter with the DNA-binding site CON and these effects depend on the
      amount of p53 expressed. Both in Saos2 and Cos7 cells, lower concentrations of
      p53 lead to activation and higher concentrations lead to repression of the model
      promoter containing the consensus p53-binding site CON. The N-terminal part of
      p53 is necessary for the transcriptional activation. It is not needed, however,
      for the repression of the same promoter, indicating that different domains of p53
      are involved in activation and repression.

PMID- 8575442
TI  - NMR studies and restrained-molecular-dynamics calculations of a long A+T-rich
      stretch in DNA. Effects of phosphate charge and solvent approximations.
AB  - The nonamer duplex d(GCAAAAACG).d(CGTTTTTGC) was studied by 1H-NMR at 500 MHz.
      With the exception of the H5' and H5" sugar protons, all protons were assigned by
      two-dimensional NMR experiments [NOE spectroscopy (NOESY), double-quantum
      filtered J-correlated spectroscopy (DQF-COSY) and total correlation spectroscopy
      (TOCSY)]. The exchange kinetics of the imino protons of the Watson-Crick base
      pairing were studied at 15 degrees C by measuring inversion-recovery rates under
      conditions of extensive ammonia base catalysis. Extrapolation to infinite base
      concentration gave anomalous long lifetimes for the A-tract in accordance with
      previous results [Leroy, J.-L., Charettier, E., Kochoyan, M. & Gueron, M. (1988)
      Biochemistry 27, 8894-8898]. On average, 11 NOESY distance constraints/nucleotide
      were evaluated using the complete relaxation matrix approach. Deoxyribose
      coupling constants were obtained from simulations of the DQF-COSY cross-peaks,
      assuming a rapid two-state equilibrium between a C2'-endo and C3'-endo conformer.
      The sugars were found to be predominantly in the C2'-endo conformation. The NMR
      derived distance and torsion constraints were implemented into three different
      restrained-molecular-dynamics (rMD) protocols, two in vacuo, with different
      charges on the phosphate group and the third with the solvent explicitly
      included. All protocols displayed good convergence from different starting
      structures. The structures derived from the three protocols satisfied
      experimental restraints equally well and had similar final energies. Although the
      overall pattern of sequence dependence of helical parameters shows some
      resemblance in all structures, we find that the absolute amplitudes of the
      parameters are largely dependent on the rMD protocols, particularly the twist
      parameters. The minor groove distance P(n + 2)-P(m + 2) varies from 0.7 nm to 1.2
      nm in the three protocols. Still the NOESY-derived anomalously short distances
      AH2(n)-H1'(m + 1) and AH2(n)-H1'(n + 1), n and m denote complementary residues,
      which are assumed to be indicative of a compressed minor groove, are kept in all
      calculated structures.

PMID- 8575443
TI  - Identification of mRNAs that show modulated expression during colon carcinoma
      cell differentiation.
AB  - To investigate the working hypotheses that stem cells or their early descendants
      are prime targets for neoplastic transformation, and that the degree to which a
      neoplasm retains the immature phenotype is an important determinant of tumor
      aggressiveness, we have identified several mRNAs that are downregulated during
      the in vitro differentiation of HT29-D4 colon carcinoma cells. These genes
      include heat-shock cognate protein Hsc70, adenylosuccinate lyase,
      B23/nucleophosmin, alpha-tubulin, and a novel gene designated DS-1. The DS-1 mRNA
      has a length of approximately 0.9 kb and is downregulated 4.7-fold upon
      differentiation. From the DS-1 cDNA, a protein of 206 amino acids with a
      molecular mass of 24 kDa and an isoelectric point of 10.9 can be deduced. An
      antiserum directed against a synthetic peptide detected a minor band of the
      expected size in Western blots, as well as a major band of lower size that may
      represent a processed form of the protein.

PMID- 8575444
TI  - Effects of poliovirus 2A(pro) on vaccinia virus gene expression.
AB  - The effects of transient expression of poliovirus 2A(pro) on p220 cleavage in COS
      cells have been analyzed. When 2A(pro) was cloned in plasmid pTM1 and transiently
      expressed in COS cells, efficient cleavage of p220 occurred after infection of
      these cells with a recombinant vaccinia virus bearing phage T7 RNA polymerase.
      High numbers of COS cells were transfected with pTM1-2A, as judged by p220
      cleavage, thereby allowing an analysis of the effects of poliovirus 2A(pro) on
      vaccinia virus gene expression. A 40-50% cleavage of p220 by transfected
      poliovirus 2A(pro) was observed ten hours post infection and cleavage was almost
      complete (80-90%) 20-25 hours post infection with vaccinia virus. Profound
      inhibition of vaccinia virus protein synthesis was detectable ten hours post
      infection and was maximal 20-25 hours post infection. This inhibition resulted
      from neither a blockade of transcription of vaccinia virus nor a lack of
      translatability of the mRNAs present in cells that synthesize poliovirus 2A(pro).
      Addition of ara-C inhibited the replication of vaccinia virus and allowed the
      continued synthesis of cellular proteins. Under these conditions, 2A(pro) is
      expressed and blocks cellular translation. Finally, p220 cleavage by 2A(pro) did
      not inhibit the translation of a mRNA encoding poliovirus protein 2C, as directed
      by the 5' leader sequences of encephalomiocarditis virus. Therefore, these
      findings show a correlation between p220 cleavage and inhibition of translation
      from newly made mRNAs. Our results are discussed in the light of present
      knowledge of p220 function, and new approaches are considered that might provide
      further insights into the function(s) of initiation factor eIF-4F.

PMID- 8575445
TI  - Synthesis and characterization of a monomeric mutant Cu/Zn superoxide dismutase
      with partially reconstituted enzymic activity.
AB  - A monomeric analog of human Cu/Zn superoxide dismutase (F50E/G51E SOD),
      previously characterized and found to have reduced enzymic activity, was here
      further modified by replacing Glu133 with Gln. This substitution does not
      dramatically affect the coordination geometry at the active site, but enhances
      enzymic activity, and also increases the affinity for anions at the active site.
      This behavior parallels earlier published results in which this point mutation
      was made in the dimeric wild-type enzyme. The analog described here has afforded
      for the first time a monomeric superoxide dismutase with substantial activity.
      This point mutation does not significantly influence the protein structure but
      interactions with anions, including superoxide, are altered with respect to the
      monomeric form. The present monomeric Glu133Gln mutant has partially restored
      enzymic activity. The diminished activity of the monomeric analogs is discussed
      in the light of possible minor structural changes and some of their
      characteristics are compared with those of naturally occurring mutants associated
      with various neurological diseases.

PMID- 8575446
TI  - The interaction between lipoamide dehydrogenase and the peripheral-component
      binding domain from the Azotobacter vinelandii pyruvate dehydrogenase complex.
AB  - The sensitivity of lipoamide dehydrogenase (dihydrolipoamide:NAD+ oxidoreductase
      E3) from Azotobacter vinelandii to inhibition by NADH requires measurement of the
      activity in the initial phase of the reaction. Stopped-flow turnover experiments
      show that kcat is 830 s-1 compared with 420 s-1 found in standard steady-state
      experiments. Mutations at the si-side of the flavin prosthetic group that cause
      severe inhibition by NADH were studied. Tyr16 was replaced by phenylalanine and
      serine, which causes the loss of two intersubunit H-bonds. [F16]E3 shows only
      5.7% of wild-type activity in the standard assay procedure, but analyzed by
      stopped-flow the activity is 70% of the wild-type enzyme. The NADH-->Cl2Ind
      (dichloroindophenol) activity was normal or slightly increased. The inhibition by
      NADH is competitive with respect to NAD+, Ki = 50 microM. Spectral analysis show
      that electrons readily pass over from the disulfide to the FAD, indicating an
      increase in the redox potential of the flavin. It is concluded that subunit
      interaction plays an important role in the protection of the enzyme against over
      reduction by decreasing the redox potential of the flavin. The interaction of
      wild-type or mutant enzymes with the core component of the pyruvate (E2p) or
      oxoglutarate (E2o) dehydrogenase multienzyme complex relieves the inhibition to a
      large extent. In the mutant enzymes, the mechanism of inhibition changes from
      competitive to the mixed-type inhibition observed for the wild-type enzyme. The
      stabilizing effect of E2 on [F16]E3 was used as an assay to analyze the
      stoichiometry of interaction of E3 with E2p as well as E2o. 1 mol E2p monomer was
      sufficient to saturate 1 mol E3 dimer with a Kd of about 1 nM. Similarly, 1 mol
      E2o saturated the E3 dimer with a Kd of 30 nM. From these experiments it is
      concluded that the E3-binding domain of E2 interacts with the subunit interface
      of E3 near the dyad axis, thus preventing sterically the interaction with a
      second molecule of the binding domain. This mode of interaction, which causes
      asymmetry in the complex, explains the stabilization against over-reduction by
      tightening the subunit interaction. Subgene cloning of the E2p component of the
      pyruvate dehydrogenase complex is described in order to obtain a complex between
      the lipoamide dehydrogenase component (E3) and the binding domain of E2p. A
      unique restriction site in the DNA encoding the flexible linker between the third
      lipoyl domain and the binding domain combined with timed digestion with
      exonuclease Bal31 was used to create a set of deletion mutants in the N-terminal
      region of the binding-catalytic didomain, fused to six N-terminal amino acids
      from beta-galactosidase. The expressed proteins, selected for E2p activity, were
      analyzed for binding of E3 and E1p. The shortest fusion protein containing a
      functional binding domain was expressed and purified. [F16]E3 was combined with
      this fusion protein in a stoichiometric ratio and the resulting complex was
      subjected to limited proteolysis to remove the catalytic domain. The resulting
      [F16]E3-binding domain preparation was purified to homogeneity.

PMID- 8575447
TI  - Characterization of a life-cycle-stage-regulated membrane protein tyrosine
      phosphatase in Trypanosoma brucei.
AB  - We report the first characterization of plasma-membrane-bound tyrosine
      phosphatase activity in the haemoprotozoan. Trypanosoma brucei. Several enzymic
      properties of the membrane fraction were identical to other protein tyrosine
      phosphatases (PTPases), such as (a) insensitivity to inhibitors of other protein
      phosphatases, including tetramisole, sodium tartrate and okadaic acid, (b)
      inhibition by sodium vanadate, and (c) activation by spermidine. Additionally, T.
      brucei PTPase activity presented two novel features, an acidic pH optimum at pH
      4.0-5.0 and a very low Km value (2.5 nM) for the specific synthetic substrate,
      Tyr(P)Raytide. Higher Km values of 170 nM for Tyr(P)-RCML (RCML, reduced,
      carboxamidomethylated and maleylated lysozyme) and of 3 mM for the non-specific
      inorganic substrate p-nitrophenyl phosphate, suggested that the PTPase activity
      of T. brucei was substrate specific. Reconstitution experiments on bloodstream
      stage membrane proteins revealed that three polypeptides of 148, 115 and 72 kDa
      contained vanadate-inhibitable PTPase activity. Modulator assays revealed that
      the 72-kDa protein was responsible for the observed spermidine stimulation, but
      indicated that the modulator profile of the 148-kDa protein was most similar to
      the whole membrane fraction. Furthermore, the PTPase activity of T. brucei was
      life-cycle-stage regulated. Neither the whole membrane fraction nor the
      reconstituted proteins of the procyclic insect stage dephosphorylated tyrosine
      residues.

PMID- 8575448
TI  - The affinity and specificity of Ca(2+)-binding sites of cytochrome-c peroxidase
      from Paracoccus denitrificans.
AB  - The binding of Ca2+ to the dihaem cytochrome-c peroxidase from Paracoccus
      denitrificans was analysed by following perturbations in the visible and 1H-NMR
      spectra of both haem groups. The enzyme contains at least two types of Ca(2+)
      binding site. Site I is occupied in the isolated enzyme, binds Ca2+ with a redox
      state-independent Kd of 1.2 microM and accommodates neither Mg2+ nor Mn2+. Site
      II is unoccupied in dilute solutions of the isolated oxidised enzyme and binds
      Ca2+ cooperatively with a Kd of 0.52 mM. In the mixed valence form, the binding
      affinity increases to resemble that of site I. The cooperativity was shown by 
      Ca2+ binding to site II, the titration of haem methyl 1H-NMR resonances, and a
      half-of-sites effect observed for modification of an essential histidine with
      diethylpyrocarbonate. These are all consistent with site II being situated at the
      interface between two monomers of a dimeric enzyme. Thus the equilibrium of
      binding to site II is a reflection of the equilibrium for dimerisation and
      conditions which shift that equilibrium towards the dimer, such as increased
      ionic strength or high protein concentration, also increase Ca2+ affinity.
      Binding of Ca2+ to site II is required for formation of the active high spin
      state at the peroxidatic haem.

PMID- 8575449
TI  - Analysis of the structural organization and thermal stability of two
      spermadhesins. Calorimetric, circular dichroic and Fourier-transform infrared
      spectroscopic studies.
AB  - The CUB domain is a widespread 110-amino-acid module found in functionally
      diverse, often developmentally regulated proteins, for which an antiparallel beta
      barrel topology similar to that in immunoglobulin V domains has been predicted.
      Spermadhesins have been proposed as a subgroup of this protein family built up by
      a single CUB domain architecture. To test the proposed structural model, we have
      analyzed the structural organization of two members of the spermadhesin protein
      family, porcine seminal plasma proteins I/II (PSP-I/PSP-II) heterodimer and
      bovine acidic seminal fluid protein (aSFP) homodimer, using differential scanning
      calorimetry, far-ultraviolet circular dichroism and Fourier-transform infrared
      spectroscopy. Thermal unfolding of PSP-I/PSP-II and aSFP were irreversible and
      followed a one-step process with transition temperatures (Tm) of 60.5 degrees C
      and 78.6 degrees C, respectively. The calorimetric enthalpy changes (delta Hcat)
      of thermal denaturation were 439 kJ/mol for PSP-I/PSP-II and 660 kJ/mol for aSFP
      dimer. Analysis of the calorimetric curves of PSP-I/PSP-II showed that the entire
      dimer constituted the cooperative unfolding unit. Fourier-transform infrared
      spectroscopy and deconvolution of circular dichroic spectra using a convex
      constraint analysis indicated that beta-structure and turns are the major
      structural element of both PSP-I/PSP-II (53% of beta-sheet, 21% of turns) and
      aSFP (44% of beta-sheet, 36% of turns), and that the porcine and the bovine
      proteins contain little, if any, alpha-helical structure. Taken together, our
      results indicate that the porcine and the bovine spermadhesin molecules are
      probably all-beta-structure proteins, and would support a beta-barrel topology
      like that predicted for the CUB domain. Other beta-structure folds, such as the
      Greek-key pattern characteristic of many carbohydrate-binding protein domains
      cannot be eliminated. Finally, the same combination of biophysical techniques was
      used to characterize the residual secondary structure of thermally denatured
      forms of PSP-I/PSP-II and aSFP, and to emphasize the aggregation tendency of
      these forms.

PMID- 8575450
TI  - Recognition of tRNAPhe by phenylalanyl-tRNA synthetase of Thermus thermophilus.
AB  - The tRNA(Phe) nucleotides required for recognition by phenylalanyl-tRNA
      synthetase of Thermus thermophilus have been determined using Escherichia coli
      tRNA(Phe) transcripts with various mutations. The anticodon nucleotides are shown
      to be the most important recognition elements. The discriminator nucleotide, A73,
      involved in the recognition set of yeast, E. coli and human phenylalanyl-tRNA
      synthetases contributes only slightly to tRNA(Phe) recognition by Th.
      thermophilus phenylalanyl-tRNA synthetase. Nucleotide 20 and some tertiary
      nucleotides, including the conserved G19.C56 base pair, are proposed to
      participate in stabilization of the precise tRNA conformation required for
      efficient aminoacylation. The role of the 3'-CCA terminus, common to all tRNAs,
      in the specific interaction of tRNA with phenylalanyl-tRNA synthetase is
      discussed.

PMID- 8575451
TI  - Isolation and characterisation of a recombinant, precursor form of lysosomal acid
      alpha-glucosidase.
AB  - Glycogenosis type II (GSD II, Pompe disease) is an autosomal recessive lysosomal
      storage disease that results from a deficiency of acid alpha-glucosidase (GAA).
      Patients with this disorder are unable to break down lysosomal glycogen, which
      consequently accumulates in the lysosome. To evaluate enzyme replacement therapy
      for GSD II patients, we have expressed human GAA cDNA in Chinese hamster ovary-K1
      cells utilising a vector that places the cDNA under the transcriptional control
      of the human polypeptide chain elongation factor 1 alpha gene promoter. A clonal
      cell line that secreted precursor recombinant GAA at approximately 18 mg.l-1.day
      1 was identified. The precursor recombinant GAA was purified to homogeneity, had
      a molecular mass of 110 kDa as measured by SDS/PAGE, and was shown to have pH
      optima and kinetic parameters similar to those of GAA purified from human
      tissues. The partial N-terminal amino acid sequence of recombinant GAA conformed
      to that derived from the nucleotide sequence of the cloned cDNA. The recombinant
      enzyme was taken up by cultured fibroblasts and skeletal muscle cells from GSD II
      patients, and was shown to correct the storage phenotype. Endocytosed GAA was
      localised to the lysosome and showed evidence of intracellular processing to a
      more mature form. Activity levels increased up to twice the normal value and
      uptake was prevented if cells were cultured in the presence of mannose 6
      phosphate.

PMID- 8575452
TI  - The tungsten formylmethanofuran dehydrogenase from Methanobacterium
      thermoautotrophicum contains sequence motifs characteristic for enzymes
      containing molybdopterin dinucleotide.
AB  - Formylmethanofuran dehydrogenases are molybdenum or tungsten iron-sulfur proteins
      containing a pterin dinucleotide cofactor. We report here on the primary
      structures of the four subunits FwdABCD of the tungsten enzyme from
      Methanobacterium thermoautotrophicum which were determined by cloning and
      sequencing the encoding genes fwdABCD. FwdB was found to contain sequence motifs
      characteristic for molybdopterin-dinucleotide-containing enzymes indicating that
      this subunit harbors the active site. FwdA, FwdC and FwdD showed no significant
      sequence similarity to proteins in the data bases. Northern blot analysis
      revealed that the four fwd genes form a transcription unit together with three
      additional genes designated fwdE, fwdF and fwdG. A 17.8-kDa protein and an 8.6
      kDa protein, both containing two [4Fe-4S] cluster binding motifs, were deduced
      from fwdE and fwdG. The open reading frame fwdF encodes a 38.6-kDa protein
      containing eight binding motifs for [4Fe-4S] clusters suggesting the gene product
      to be a novel polyferredoxin. All seven fwd genes were expressed in Escherichia
      coli yielding proteins of the expected size. The fwd operon was found to be
      located in a region of the M. thermoautotrophicum genome encoding molybdenum
      enzymes and proteins involved in molybdopterin biosynthesis.

PMID- 8575453
TI  - Benzoyl-coenzyme A reductase (dearomatizing), a key enzyme of anaerobic aromatic
      metabolism. ATP dependence of the reaction, purification and some properties of
      the enzyme from Thauera aromatica strain K172.
AB  - Anoxic metabolism of many aromatic compounds proceeds via the common intermediate
      benzoyl-CoA. Benzoyl-CoA is dearomatized by benzoyl-CoA reductase (dearomatizing)
      in a two-electron reduction step, possibly yielding cyclohex-1,5-diene-1-carboxyl
      CoA. This process has to overcome a high activation energy and is considered a
      biological Birch reduction. The central, aromatic-ring-reducing enzyme was
      investigated for the first time in the denitrifying bacterium Thauera aromatica
      strain K172. A spectrophotometric assay was developed which was strictly
      dependent on MgATP, both with cell extract and with purified enzyme. The oxygen
      sensitive new enzyme was purified 35-fold with 20% yield under anaerobic
      conditions in the presence of 0.25 mM dithionite. It had a native molecular mass
      of approximately 170 kDa and consisted of four subunits a,b,c,d of 48, 45, 38 and
      32 kDa. The oligomer composition of the protein most likely is abcd. The
      ultraviolet/visible spectrum of the protein as isolated, but without dithionite,
      was characteristic for an iron-sulfur protein with an absorption maximum at 279
      nm and a broad shoulder at 390 nm. The estimated molar absorption coefficient at
      390 nm was 35,000 M-1 cm-1. Reduction of the enzyme by dithionite resulted in a
      decrease of absorbance at 390 nm, and the colour turned from greenish-brown to
      red-brown. The enzyme contained 10.8 +/- 1.5 mol Fe and 10.5 +/- 1.5 mol acid
      labile sulfur/mol. Besides zinc (0.5 mol/mol protein) no other metals nor
      selenium could be detected in significant amounts. The enzyme preparation
      contained a flavin or flavin-like compound; the estimated content was 0.3 mol/mol
      enzyme. The enzyme reaction required MgATP and a strong reductant such as
      Ti(III). The reaction catalyzed is: benzoyl-CoA + 2 Ti(III) + n ATP-->non
      aromatic acyl-CoA + 2 Ti(IV) + n ADP + n Pi. The estimated number n of ATP
      molecules hydrolyzed/two electrons transferred in benzoyl-CoA reduction is 2-4.
      In the absence of benzoyl-CoA the enzyme exhibited oxygen-sensitive ATPase
      activity. The enzyme was specific for Mg(2+)-ATP, other nucleoside triphosphates
      being inactive (< 1%). Mg2+ could be substituted to some extent by Mn2+, Fe2+ and
      less efficiently by Co2+. Benzoate was not reduced, whereas some fluoro, hydroxy,
      amino and methyl analogues of the activated benzoic acid were reduced, albeit at
      much lower rate; the products remain to be identified. The specific activity with
      reduced methyl viologen as the electron donor was 0.55 mumol min-1 mg-1
      corresponding to a catalytic number of 1.6 s-1. The apparent Km values under the
      assay conditions (0.5 mM for both reduced and oxidized methyl viologen) of
      benzoyl-CoA and ATP were 15 microM and 0.6 mM, respectively. The enzyme was
      inactivated by ethylene, bipyridyl and, in higher concentrations, by acetylene.
      Benzoyl-CoA reductase also catalyzed the ATP-dependent two-electron reduction of
      hydroxylamine (Km 0.15 mM) and azide. Some of the properties of the enzyme are
      reminiscent of those of nitrogenase which similarly overcomes the high activation
      energy for dinitrogen reduction by coupling electron transfer to the hydrolysis
      of ATP.

PMID- 8575454
TI  - A conserved histidine residue of Escherichia coli outer-membrane phospholipase A
      is important for activity.
AB  - Escherichia coli outer-membrane phospholipase A (OMPLA) is thought to be a member
      of the class of serine hydrolases, having a classical Asp-His-Ser catalytic triad
      [Horrevoets, A. J. G., Verheij, H. M. & de Haas, G. H. (1991) Eur. J. Biochem.
      198, 247-253]. To identify the histidine residue that is important for catalytic
      activity, the four histidine residues in E. coli OMPLA that are conserved in
      other enterobacterial OMPLA enzymes were replaced by cysteine residues using PCR
      directed, site-specific mutagenesis. The resulting mutant proteins were all well
      expressed and displayed heat modifiability, indicating that they were properly
      folded. Enzyme assays showed that only the His142Cys mutant protein was lacking
      enzymatic activity. In addition, a His142Gly mutant protein appeared to be
      inactive. These results show that His142 is important for the enzymatic activity
      of OMPLA.

PMID- 8575455
TI  - Structure of glycopeptides isolated from bovine milk component PP3.
AB  - The heat-stable acid-soluble phosphoglycoprotein component PP3 was isolated from
      the bovine milk proteose peptone fraction by concanavalin A affinity
      chromatography. Glycopeptides were released by pronase digestion of the milk
      component PP3 and were subsequently separated by high-pH anion-exchange
      chromatography on CarboPac PA-1. The primary structures of the glycan and peptide
      moieties of eight N-glycopeptides have been established by combining methylation
      analysis, mass spectrometry, 400-MHz 1H-NMR spectroscopy, and peptide sequence
      analysis. All the analyzed fractions contained biantennary N-acetyllactosamine
      type carbohydrate chains, some of them with a GalNAc(beta 1-4)GlcNAc or a
      NeuAc(alpha 2-6)GalNAc(beta 1-4)GlcNAc group. This particular sequence did or did
      not replace the Gal(beta 1-4)GlcNAc group usually found in most N-linked glycans.
      Moreover, the sialylated Gal and GalNAc residues were only found on the Man(alpha
      1-3) antenna.

PMID- 8575456
TI  - Lipid interaction of the 37-kDa and 58-kDa fragments of the Helicobacter pylori
      cytotoxin.
AB  - Helicobacter pylori cytotoxin vacA (95 kDa) causes a vacuolar degeneration of
      epithelial cells. There is evidence that this protein toxin acts inside cells,
      and hence has to cross a cell membrane. This cytotoxin is frequently obtained as
      two fragments of 58 kDa (p58) and 37 kDa (p37) and it is available only in minute
      amounts. Here, its membrane interaction was studied with the two fragments,
      produced in Escherichia coli. Light scattering and energy transfer experiments
      show that p37 and p58 cause aggregation and fusion of small unilamellar lipid
      vesicles; only a reversible aggregation is induced at neutral pH, whereas at acid
      pH fusion also takes place. p58, but not p37, causes potassium efflux from
      liposomes and this occurs only at acid pH. Hydrophobic photolabelling with
      photoactivatable phosphatidylcholines inserted into liposomes shows that both
      fragments are labelled at neutral pH. The amount of labelling of the two
      fragments is much higher at acid pH, consistent with a further penetration into
      the hydrophobic core of the lipid bilayer. Tryptophan fluorescence measurements
      indicate that the two fragments undergo a pH-driven conformational change. These
      data are consistent with cytotoxin entry in the cell cytosol via an intracellular
      acidic compartment.

PMID- 8575457
TI  - Translation initiation and assembly of peripherin in cultured cells.
AB  - The peripherin gene has three potential ATG translation initiation sites at
      positions 38, 56, and 290. The second ATG has been proposed to be the initiation
      codon used for translation of the protein, but there is no experimental evidence
      for this conjecture. We have isolated a full-length peripherin cDNA (designated
      as p61-11) from a rat brain cDNA library. Upon sequencing, we found that this
      cDNA contains a point mutation at the second potential translation initiation
      codon, which changes this ATG to ACG. When expressed in SW13 cl.2 vim- cells, a
      cell line without any detectable cytoplasmic intermediate filaments, the protein
      product of p61-11 cannot form a filamentous network and the major product is 45
      kDa in size, which is most likely initiated from the third ATG. The protein
      product from the first ATG (57 kDa in size) of p61-11 is also detected albeit in
      smaller amounts. We introduced a frame-shift mutation upstream of the third ATG
      in p61-11 to create p61-11FS and showed that the third ATG is able to initiate
      translation efficiently even in the presence of the first ATG, and the 45 kDa
      protein leads to a diffuse nonfilamentous staining pattern in vim- cells
      confirming that the first ATG may not be the preferred translation initiation
      codon, since it cannot suppress a downstream ATG. We increased the translation
      efficiency from the first ATG of p61-11 by mutating the three nucleotides
      preceding this first ATG and thereby placing it in a better Kozak consensus
      sequence for translation initiation. The resulting 57 kDa protein is able to form
      a filamentous network in vim- cells. We corrected the mutation in the original
      p61-11 by polymerase chain reaction and generated two peripherin constructs:
      perM1M2 (which contains all three translation initiation codons) and per delta
      1M2 (the first ATG is deleted, but the other two are present). When transfected,
      their protein products, about 57 kDa in size, form filamentous networks in the
      absence of other cytoplasmic intermediate filaments. Since there is no 45 kDa
      protein detected for these latter two constructs, it is reasonable to conclude
      that in the presence of the second ATG, little or no translation is initiated
      from the third ATG. Taken together, these results strongly suggest that the
      second ATG is the preferred translation initiation codon for the peripherin gene.

PMID- 8575458
TI  - Golgi staining by two fluorescent ceramide analogues in cultured fibroblasts
      requires metabolism.
AB  - A fluorescent derivative of ceramide, N-(6-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)
      aminohexanoyl)-D-erythr o-sphingosine (C6-NBD-Cer), has been shown to label the
      Golgi apparatus of cultured cells (Lipsky, N. G., R. E. Pagano, Science 228, 745
      747 (1985)). There is no unequivocal explanation for this Golgi labeling which is
      important in view of photolabeling of Golgi proteins which might be involved in
      metabolism, sorting and transport of (glyco)sphingolipids. To gain more insight
      into the mode of accumulation of this fluorescent ceramide analogue in the Golgi
      apparatus, we have synthesized two novel derivatives of C6-NBD-Cer, namely its 1
      O-methyl and 3-O-methyl ether, and studied their uptake by and metabolism as well
      as intracellular distribution in cultured fibroblasts. Like C6-NBD-Cer both of
      these methyl ethers were able to diffuse across the plasma membrane at 7 degrees
      C and to label intracellular membranes. Within the first 30 min no conspicuous
      labeling of the Golgi apparatus was to be seen suggesting that all three ceramide
      analogues have no distinct affinity to this organelle. However, C6-NBD-Cer as
      well as the 3-O-methyl-C6-NBD-Cer slowly gave rise to labeling of Golgi membranes
      when the temperatures was maintained at 7 degrees C. With this increasing Golgi
      labeling a concomitant formation of C6-NBD-glucosylceramide and C6-NBD
      sphingomyelin as well as 3-O-methyl-C6-NBD-sphingomyelin was observed. This
      demonstrates that the observed Golgi labeling is due to the formation of the
      respective fluorescent metabolites rather than to the fluorescent ceramide
      analogues themselves. This idea is consistent with our finding that when 1-O
      methyl-C6-NBD-Cer was used neither formation of metabolites nor labeling of Golgi
      membranes could be observed even if the temperature was raised to 37 degrees C.

PMID- 8575459
TI  - Antisense p53 provokes changes in HeLa cell growth and morphology.
AB  - Human cervical carcinoma HeLa cells, containing the wild-type p53 protein, were
      stably transfected with a p53 antisense encoding plasmid. Differences in the p53
      content in extracts from the p53 antisense transfected HeLa clones compared to
      the parental HeLa cells were demonstrated by protein binding to the p53 consensus
      oligonucleotide and in transactivation assays. Striking morphological alterations
      were observed in several HeLa clones stably transfected with the p53 antisense
      encoding plasmid. Giant multinucleated cells appeared several passages after
      transfection in four p53 antisense transfected HeLa clones derived from three
      independent transfection experiments, and were not observed in parental HeLa
      cells, or in p53 sense or vector-transfected HeLa clones. A strong growth
      inhibitory effect was observed for the HeLa clones stably transfected with p53
      antisense encoding plasmid. Reconstitution experiments with HeLa cells treated
      with a short p53 antisense oligonucleotide gave similar results: growth
      inhibition and giant cells. These giant multinucleated cells were negative for
      [3H]thymidine incorporation and displayed dispersed nuclear staining for
      proliferating cell nuclear antigen, indicating the absence of DNA replication.

PMID- 8575460
TI  - Two conserved serines in the nuclear localization signal flanking region are
      involved in the nuclear targeting of human lamin A.
AB  - The nuclear lamins are karyophilic proteins located at the nucleoplasmic surface
      of the inner nuclear membrane. We have constructed mutants immediately N-terminal
      to the nuclear localization signal of human lamin A to identify sites regulating
      the nuclear transport of the protein. Using an in vitro transport assay, we
      determined the short-term kinetics of nucleocytoplasmic transport of wild type
      and mutant proteins. The double mutation of two putative protein kinase C sites
      (serine 403/404-->alanine) reduced the rate of nuclear import for the mutant
      protein. Inhibition of phosphorylation in wild type lamin A by the specific
      protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7)
      and staurosporine or treatment with acid or alkaline phosphatase decreased the
      nuclear import of the protein. We suggest that transport of human lamin A into
      the nucleus is regulated by phosphorylations of protein kinase C sites in the
      sequence N-terminal to the nuclear localization signal.

PMID- 8575461
TI  - Pericentriolar targeting of GDP-dissociation inhibitor isoform 2.
AB  - Cellular mechanisms for regulating membrane movements appear to involve small
      GTPases of the Rab subfamily. Binding of GDP-bound Rab proteins to donor
      membranes and their release from target membranes appear to be regulated by GDP
      dissociation inhibitor (GDI) protein isoforms. Previous work showed strikingly
      higher levels of GDI-2 than GDI-1 fractionate with total membranes of cultured
      cells and are visualized in the perinuclear region in 3T3-L1 adipocytes. Here we
      report that GDI-2-containing structural elements are concentrated predominantly
      in the pericentriolar area in interphase CHO-T cells and differentiated 3T3-L1
      adipocytes based on colocalization of GDI-2 and the centrosomal marker
      pericentrin. This finding is documented by both immunofluorescence and
      immunoelectron microscopy. Expressed c-Myc-tagged GDI-2 in transfected COS-7
      cells targets to the same region. During mitotic resolution of the centrosome
      into two identifiable foci in CHO-T cells, GDI-2 containing structures remain
      intact and also resolve into two regions surrounding the centrosome. Dissociation
      of pericentriolar GDI-2 from the Golgi markers beta-COP and lectin receptors was
      apparent upon brefeldin A treatment of 3T3-L1 adipocytes or CHO-T cells. The
      integrity of pericentriolar GDI-2-binding elements was not disrupted by either
      brief Triton X-100 extraction or microtubule cytoskeletal disassembly, achieved
      with nocodazole. These data demonstrate the presence of highly ordered, detergent
      resistant GDI-2-specific structural elements around the centrosome and indicate
      functional differences for the GDI-1 and GDI-2 protein isoforms. The results
      suggest the presence of selective GDI-2 acceptors in this region and a possible
      role of pericentriolar GDI-2 in membrane recycling.

PMID- 8575462
TI  - Neurothelin: amino acid sequence, cell surface dynamics and actin colocalization.
AB  - Neurothelin is a cell surface protein of chicken endothelial cells at the blood
      brain barrier and also of pigment epithelial cells forming the blood-eye barrier.
      Peptide sequencing of affinity-purified neurothelin revealed that it is likely to
      be identical with the protein called HT7. It belongs to the immunoglobulin
      superfamily having two extracellular C2-type domains, a membrane spanning region
      and a cytoplasmic tail. During development neurothelin cell surface localization
      changed on pigment epithelial cells. In early embryogenesis neurothelin was found
      preferentially at lateral sites of neighboring epithelial cells, but after
      hatching, predominantly on basal cell surfaces and on apical microvilli of
      epithelial cells that contact retinal photoreceptors. Disruption of cell-cell
      contacts induced a rapid change of neurothelin distribution on the cell surface
      in vitro as could be shown by confocal laser microscopy. Disintegration of
      microfilaments by cytochalasin D hampered this specific cell surface
      rearrangement of neurothelin, whereas depolymerization of microtubules by
      demecolcine had no effect. In double-labeling experiments neurothelin and F-actin
      were colocalized. The data suggest that the polarized cell surface distribution
      of neurothelin is influenced intracellularly by F-actin and extracellularly by
      cell-cell interactions.

PMID- 8575463
TI  - Phagocytic processing of the macrophage endoparasite, Mycobacterium avium, in
      comparison to phagosomes which contain Bacillus subtilis or latex beads.
AB  - The intraphagosomal survival strategy of pathogenic mycobacteria was studied in
      bone marrow-derived mouse macrophages. These bacteria survive inside phagosomes
      by interfering in an unknown manner with phagosome processing which normally
      would lead to digestion of the phagocytic particle in phagolysosomes. Here,
      phagosome processing was compared for different phagocytic particles: live
      Mycobacterium avium, degradable Bacillus subtilis, or indigestible latex beads.
      We show detailed electron microscopic morphological observations which
      characterize various phases of interaction between endocytic organelles and
      phagosomes. We measured fusion of phagosomes with early endosomes or with
      lysosomes by using newly internalized endocytic contents (horseradish peroxidase,
      HRP) and membrane marker (plasma membrane glycoconjugates labeled with
      [3H]galactose via exoglycosylation). Morphometric analysis of these observations
      showed that the nature of the phagocytic particle affects phagosome processing:
      As long as particles remain undigested, maturation of phagosomes is prevented and
      they remain fusogenic towards early endosomes; concurrent to particle digestion,
      phagosome processing proceeds towards transfer of phagocytic contents to
      phagolysosomes which display kinetic and compositional characteristics of
      lysosomes. As an intact phagocytic particle, M. avium remains in non-matured
      phagosomes which fuse with early endosomes, but not with lysosomes. Fusion with
      early endosomes is reduced, thereby indicating the stage where this endoparasite
      exerts its effect.

PMID- 8575464
TI  - The formation of compound granules from different types of secretory organelles
      in human platelets (dense granules and alpha-granules). A cryofixation/
      substitution study using serial sections.
AB  - The secretory pathway of dense granule contents in cryofixed and cryosubstituted
      human platelets was investigated by electron microscopy of serial sections. The
      spherical dense granules in resting platelets were separated by cytoplasm. No
      contact between these granules and the plasmalemma or the membranes of alpha
      granules or other membranes could be observed. Stimulated platelets (thrombin,
      0.1-0.5 IU/ml for 20-30 sec) contained dense granules with long protrusions.
      Tight contacts between the membranes of these granules with the plasmalemma and
      with membranes of alpha-granules were detected (apposition). Fusion events took
      place at these sites. After fusion of the dense granules with the plasmalemma the
      organelles were swollen and contained remnants of their dense matrix. After
      fusion between dense and alpha-granules compound granules were formed which
      included remnants of matrices from both types of organelles. It is concluded that
      the secretory pathway is similar for both types of organelles.

PMID- 8575465
TI  - Localization of proteasomal antigens during different phases of the cell cycle in
      HeLa cells.
AB  - We localized two different proteasome-associated epitopes with the use of two
      specific monoclonal antibodies, MCP21 and anti-p25, in interphase and mitotic
      HeLa cells cultured in vitro. We provide evidence for an association of those
      antigens with the spindle poles in metaphase and with the midbody region in
      anaphase and telophase. Triton-nonextractable structures are also labeled in
      interphase. Moreover, the labeling pattern of interphase cells obtained with the
      monoclonal antibodies MCP21 and anti-p25 differs considerably, and in the case of
      MCP21 displays clear cell cycle-specific changes: nuclear labeling is absent or
      very weak in G1 and S phases of the cell cycle, whereas it is strong in G2 phase.
      This might reflect the existence of different subpopulations of proteasomes in
      the cell.

PMID- 8575466
TI  - Differential response of resident proteins and cycling proteins of the Golgi to
      brefeldin A.

PMID- 8575467
TI  - The murine replication protein P1 is differentially expressed during
      spermatogenesis.

PMID- 8575468
TI  - Oncology and nuclear medicine: a developing collaboration.

PMID- 8575469
TI  - Correlation of the findings of thallium-201 chloride scans with those of other
      imaging modalities and histology following therapy in patients with bone and soft
      tissue sarcomas.
AB  - We performed a retrospective [corrected] study to evaluate the imaging potential
      of thallium-201 as compared with other imaging modalities in differentiating
      residual/recurrent tumors from post-therapy changes in patients with
      musculoskeletal sarcomas. 201Tl scans, magnetic resonance imaging (17), X-ray
      computed tomography (6) or contrast angiography (6) studies in 29 patients
      previously treated for musculoskeletal sarcomas were correlated with either
      histopathologic findings (26 patients) or 2-year clinical follow-up (three
      patients). All imaging studies were acquired within 2 weeks. Ratios of 201Tl
      tumor uptake to the contralateral (28 patients) or adjacent region of interest
      were calculated. When qualitative interpretation was in doubt, only those cases
      with a ratio of 1.5 or more were considered suggestive of recurrent of residual
      viable tumor tissue. Residual or recurrent tumor tissue was verified in 21
      patients by biopsy. All had true-positive 201Tl scans while the other imaging
      modalities were true-positive in 20 and equivocal in one. In eight patients,
      there was no evidence of viable tumor tissue as proven by biopsy in five and long
      term clinical follow-up in three. 201Tl scan was false-positive (ratio 1.5) in
      one patient and true-negative in seven while the other imaging modalities had
      four false-positives. The average 201Tl ratios were 2.8+/-1.1 in the true
      positive cases and 1.3+/-0.3 in the true-negative cases. The percentage
      sensitivities, specificities, and accuracy for 201Tl were 100%, 87.5%, and 96.5%
      versus 95%, 50%, and 82.7% respectively for other imaging modalities. These
      results indicate that 201Tl scintigraphy is more accurate than other imaging
      modalities in differentiating residual/recurrent musculoskeletal sarcomas from
      post-therapy changes.

PMID- 8575470
TI  - The impact of dynamic lymphoscintigraphy and gamma probe guidance on sentinel
      node biopsy in melanoma.
AB  - In cutaneous melanoma, biopsy of the first tumour-draining lymph node (sentinel
      node, SN) may replace routine elective lymph node dissection (ELND). Even in
      experienced hands the original technique using vital dyes fails to localise the
      SN in 20% of cases. In this study we investigated whether the procedure benefits
      from lymphoscintigraphy and the use of a gamma probe. In 41 patients technetium
      99m-colloidal albumin was injected intracutaneously around the scar of the
      excised tumour. This was followed by dynamic and late static imaging. The first
      focal accumulation was assumed to be the SN. In all patients at least one SN was
      found, in 95% within the first 20 min. By showing multiple or ramifying lymphatic
      channels, dynamic lymphoscintigraphy differentiated between spill and multiple
      SNs. In all cases the initial focus retained the highest fraction of
      radioactivity for at least 18 h. The gamma probe was especially useful in the
      axilla and neck, where it accurately showed the optimal incision site and
      facilitated the search for deep-seated nodes. Gamma probe-localised SNs were dye
      positive in 93% of cases. The SN contained metastases in 20% of the patients.
      Only in these patients was ELND performed, which revealed that the SN had been
      the only metastatic node in four of eight cases. We conclude that dynamic
      lymphoscintigraphy is essential for SN localisation, that tracer kinetics allow
      flexible timing of surgery, and that the surgical procedure benefits from use of
      the gamma probe.

PMID- 8575471
TI  - Continuous intraoperative external monitoring of perfusate leak using iodine-131
      human serum albumin during isolated perfusion of the liver and limbs.
AB  - Regional isolated perfusion using tumor necrosis factor (TNF) shows significant
      promise for treatment of cancer which is limited to limbs or organs. The high
      toxicity of TNF requires very sensitive real time monitoring of leakage in order
      to avoid serious patient complications. Human serum albumin labeled with iodine
      131 is used with an externally mounted and collimated NaI(Tl) detector to track
      the leakage of blood from the isolated perfusion blood circuit into the general
      systemic vascular space. Blood activity levels measured using the monitor
      demonstrated a very good correlation with blood serum samples taken concurrently
      with external monitoring. External monitoring can reduce the risks of perfusion
      leakage intraoperatively with the precision necessary to safely perform isolated
      perfusion using TNF.

PMID- 8575472
TI  - Specific targeting of infectious foci with radioiodinated human recombinant
      interleukin-1 in an experimental model.
AB  - In the present study, radioiodinated human recombinant interleukin-1 (IL-1) was
      investigated for its potential to image infectious foci in vivo in an animal
      model of infection. Twenty-four hours after induction of a Staphylococcus aureus
      abscess in the left calf muscle, mice were i.v. injected with both iodine-125
      labelled IL-1 and iodine-131 labelled myoglobin, a size-matched control agent.
      The animals were killed for tissue biodistribution studies at 2, 6, 12, 24 and 48
      h p.i. Gamma camera images were obtained at 6, 24 and 48 h after injecting mice
      with 123I-IL-1. Radioiodinated IL-1 rapidly cleared from the body; after 12 h the
      abscess was the organ with the highest activity. The absolute abscess uptake of
      125I-IL-1 remained high compared to 131I-myoglobin, resulting in significantly
      higher abscess-to-muscle ratios of 125I-IL-1 compared to 131I-myoglobin. The
      ratios of 125I-IL-1 reached the ultimate value of 44.4+/-10.8 at 48 h p.i.,
      whereas the ratios of 131I-myoglobin did not exceed 5.9+/-0.7. Gamma camera
      imaging revealed clearly visible abscesses. In conclusion, our results
      demonstrate specific retention of radioiodinated IL-1 in the abscess, presumably
      by interaction of IL-1 with its receptor on the inflammatory cells. The high
      target-to-background ratios that were obtained over the course of time indicate
      that the IL-1 receptor may be a valuable target for the imaging of infectious
      foci.

PMID- 8575473
TI  - Impairment of the exercise-induced increase in muscle perfusion in McArdle's
      disease.
AB  - In McArdle's disease (myophosphorylase deficiency) exercise intolerance is
      generally attributed to a lack of glycogenolysis, which decreases energy
      production during exercise. Magnetic resonance imaging data have recently
      suggested an impairment of the increase in muscle perfusion during exercise in
      these patients. We have tested this hypothesis by direct measurement of local
      muscle perfusion increase. Increase in muscle perfusion was assessed by positron
      emission tomography with oxygen-15 labelled water in five patients with McArdle's
      disease and five age- and sex-matched healthy volunteers. Radioactivity was
      measured in both forearms before and after exercise of the right forearm. The
      exercise intensity was biochemically assessed by in vivo phosphorus-31 magnetic
      resonance spectroscopy. The estimated increase in muscle perfusion with exercise
      was 5.7+/-5.5-fold in the patients (range 1.5-12.8) and 22.3+/-12.0-fold in the
      healthy subjects (range 10.1-37) (P=0.022). The results show a significant
      impairment of increase in muscle perfusion with exercise in McArdle's disease.
      Thus patients may suffer not only from a direct lack of glycogenolysis but also
      from indirectly impaired vasodilation.

PMID- 8575474
TI  - Comparison of mean cerebral transit time and single-photon emission tomography
      for estimation of stroke outcome.
AB  - Mean cerebral transit time (MCTT) scanning is a possible alternative to cerebral
      single-photon emission tomography (SPET) for early assessment of cerebral
      perfusion after acute ischaemic stroke. Although MCTT is rapid, inexpensive and
      does not require sophisticated equipment, the relationship between MCTT and
      functional outcome is unknown. This study aimed to compare the effectiveness of
      SPET and MCTT in the prediction of functional outcome. Sixty-three patients
      undergoing cerebral computed tomography (CT), technetium-99m MCTT, and technetium
      99m-labelled hexamethylpropylene amine oxime SPET soon after acute ischaemic
      stroke had outcome assessed after 3 months. Cerebral CT, SPET and MCTT scans were
      interpreted without reference to the clinical data; a single independent observer
      assessed outcome using the Barthel Index. The 3-month Barthel score in survivors
      was significantly correlated with volume of lesion on SPET (Spearman's r=-0.425,
      P<0.005) and with the ratio of mean affected hemisphere transit times to mean
      unaffected hemisphere transit times (Spearmen's r=-0.356, P <0.01), but not with
      CT lesion volume (Spearman's r = -0.175, P >0.1). Stepwise logistic regression
      identified volume of lesion on SPET as the only significant predictor of good
      functional outcome (Barthel score>70). The overall predictive accuracy was 73%.
      It is concluded that MCTT, although significantly correlated with functional
      outcome, failed to predict good functional recovery in individual stroke
      survivors. Since SPET provides more detailed localisation of perfusion deficits,
      and since SPET lesion volume can be used to predict functional outcome, SPET
      remains preferable to MCTT when perfusion imaging is required.

PMID- 8575475
TI  - Changes in cerebral blood flow induced by balloon test occlusion of the internal
      carotid artery under hypotension.
AB  - Balloon test occlusion (BTO) of the internal carotid artery (ICA) combined with
      cerebral blood flow (CBF) study has proved to be a sensitive test for prediction
      of the outcome of permanent vessel occlusion. In this study, we evaluated the
      acute changes in regional CBF during BTO under hypotension in order to examine
      the possible risk of cerebral ischaemia after surgical treatment. Eleven patients
      in whom surgical carotid sacrifice was planned underwent BTO combined with CBF
      studies using technetium-99m hexamethyl-propylene amine oxime single-photon
      emission tomography under hypotension by decreasing the systemic blood pressure
      by about 50 mm Hg using a ganglion blocking agent. All patients showed a mild to
      severe decrease in CBF in the ipsilateral ICA territory relative to the
      contralateral side. A decrease in CBF of greater than 20% was observed in nine
      patients (82%), and two of them showed a decrease exceeding 40%. However, no
      ischaemic symptoms were demonstrated during scanning with hypotensive BTO. Our
      results suggest that in many patients with negative normotensive BTO, a
      considerable reduction in CBF would occur during hypotension. This procedure may
      predict a possible risk of hypotensive accident during and/or after surgery.

PMID- 8575476
TI  - Brain single-photon emission tomography with technetium-99m hexamethylpropylene
      amine oxime in adolescents with initial-stage schizophrenia.
AB  - The objective of this study was to search for regional cerebral blood flow (rCBF)
      abnormalities in adolescents with initial-stage schizophrenia by means of brain
      single-photon emission tomography (SPET) using technetium-99m hexamethylpropylene
      amine oxime (HMPAO). SPET studies were performed on a homogeneous sample of 15
      carefully selected adolescents with a recent diagnosis of schizophrenia, and
      without previous electroconvulsive or antipsychotic drug treatment. Computed
      tomography (CT) and electro-encephalographic (EEG) studies were performed in all
      patients. Qualitative and semiquantitative analysis of 99mTc-HMPAO SPET studies
      showed an impaired rCBF in 12 patients (80%). The most common pattern was a
      decreased uptake of 99mTc-HMPAO in the frontal lobes, usually in the left
      hemisphere. Conventional and quantitative EEG was positive in 12 (80%) and 15
      (100%) patients, respectively. CT findings were positive in two patients (13%).
      There was a high level of concordance between SPET and EEG results and between
      SPET and clinical features (P>0.05). This study suggests that previously
      untreated patients in the first stages of schizophrenia present functional
      abnormalities that are revealed by brain SPET.

PMID- 8575477
TI  - Technetium-99m mercaptoacetyltriglycine clearance: reference values for infants
      and children.
AB  - Six hundred and thirty-nine clearance studies performed in children aged 7 days
      to 19 years utilizing technetium-99m mercaptoacetyltriglycine (MAG 3) were
      retrospectively analysed. Standardized conditions for the investigation included:
      parenteral hydration (60 ml/hxm2 body surface) in addition to normal oral fluid
      intake, weight-related dose of 99mTc-MAG 3 (1 MBq/kg body weight, minimum 15 MBq)
      and calculation of clearance according to Bubeck et al. Of the 513 children, 169
      included in this analysis could be classified as "normal" with regard to their
      renal function. Normal kidney function was judged by the following criteria:
      normal GFR for age, normal tubular function (absence of proteinuria and
      glucosuria), normal renal parenchyma (on ultrasonography, MAG 3 scan and
      intravenous pyelography), absence of significant obstruction and gross reflux
      (>grade I), no single kidney and no difference in split renal function >20%.
      Results showed increasing MAG 3 clearance values for infants during the first
      months of life, reaching the normal range for older children and adults between 7
      and 12 months.

PMID- 8575478
TI  - Delayed gastric emptying and Helicobacter pylori infection in patients with
      chronic renal failure.
AB  - Forty patients with chronic renal failure (CRF) were enrolled in this study.
      Twelve of the 40 patients had upper gastrointestinal symptoms or signs (GI Sx).
      Twenty of the 40 patients had been receiving regular haemodialysis (HD) for at
      least 1 year prior to the study. Radionuclide-labelled solid meals were used to
      calculate gastric emptying times (GETs). The carbon-14 urea breath test (14C4
      UBT) was used to diagnose Helicobacter pylori (HP) infection. Among the 40
      patients, 35 (88%) had an abnormal GET and 22 (55%) had a positive 14C-UBT for HP
      infection. There were no statistically significant differences in the incidence
      of abnormal GET among patients with HP infection and patients without HP
      infection. There were also no significant differences in the incidence of HP
      infection among patients with abnormal and normal GETs. In addition, the
      incidences of abnormal GET in patients with and without upper GI Sx were 83% and
      89% respectively. The incidences of HP infection in patients with and without
      upper GI Sx were 58% and 54%, respectively. The incidences of abnormal GET in HD
      and non-HD patients were 95% and 80%, respectively. The incidences of HP
      infection in HD and non-HD patients were 45% and 65%, respectively. The
      differences in the incidences of abnormal GET and HP infection among HD and non
      HD patients, as well as among patients with and without upper GI Sx, were not
      statistically significant.

PMID- 8575479
TI  - Assessment of acute myocardial necrosis after cardiopulmonary resuscitation and
      cardioversion by means of combined thallium-201/technetium-99m pyrophosphate
      tomography.
AB  - Diagnosis of acute myocardial necrosis by means of conventional
      electrocardiographic criteria or the release of cardiac enzymes is often
      difficult or even impossible in patients with out-of-hospital cardiac arrest due
      to ventricular fibrillation with subsequent cardiopulmonary resuscitation
      including several DC countershocks. Simultaneous thallium-201/technetium-99m
      pyrophosphate (PYP) tomography was prospectively applied to 57 patients without
      typical clinical or electrocardiographic signs of acute myocardial infarction
      within 48 h after successful resuscitation from out-of-hospital cardiac arrest.
      Scintigraphic evidence of acute necrosis was present in 23/57 patients (40%).
      Increased 99mTc-PYP uptake in the pericardial tissue was found in 24 patients
      (42%). Maximal creatine kinase (CK) concentration was increased in 50/57 patients
      (88%). CK-MB activity averaged 68+/-52 U/l in patients with positive and 17+/-13
      U/l in patients with negative tomograms (P<0.0005), demonstrating the validity of
      201Tl/99mTc-PYP tomography. It may be concluded that simultaneous 201Tl/99mTc-PYP
      tomography is a valuable tool for evaluation of myocardial necrosis after
      cardiopulmonary resuscitation including DC countershock. Acute myocardial
      necrosis, as indicated by scintigraphy, represents a potential trigger for the
      occurrence of ventricular fibrillation. Therefore, 201Tl/99mTc-PYP tomography can
      be recommended in order to guide further diagnostic and therapeutic interventions
      in patients after cardiopulmonary resuscitation in whom the underlying cause of
      the occurrence of ventricular fibrillation is obscure.

PMID- 8575480
TI  - Radionuclide angiography and magnetic resonance imaging: complementary non
      invasive methods in the diagnosis of constrictive pericarditis.
AB  - Constrictive pericarditis presents with a suggestive clinical picture, and its
      diagnosis is based on a haemodynamic pattern revealing impaired ventricular
      filling. In this study of 15 patients with pure isolated constrictive
      pericarditis, we attempted to evaluate the diagnostic value of two non-invasive
      methods not usually employed in this indication: radionuclide angiography (RNA)
      and magnetic resonance imaging (MRI). Whilst RNA permits analysis of the
      functional pattern of the global and segmental left ventricular filling
      impairment, MRI allows measurement of the thickness of the pericardium. RNA
      revealed increased early diastolic filling as evidenced by a shorter one-third
      filling time (TF1/3; P<0.0001 with respect to a normal population), a higher peak
      filling rate (PFR; P<0.01) and its early occurrence (P<0.001), increased one
      third and mid diastolic filling fractions (P<0.01), and the ratio of the PFR over
      the peak ejection rate (P<0.01). During late diastole, the atrial filling
      fraction decreased (NS). The patients with constrictive pericarditis also showed
      a decrease in the physiological filling asynchrony, as assessed by segmental
      evaluations. Seven patients underwent MRI. The pericardium was thickened in all
      the patients, varying from 6 to 14 mm (normal: 2.5+/-0.7 mm), without any systolo
      diastolic variation. Pericardial thickening appeared as a dark low-intensity
      signal band, demonstrating the fibrocalcific nature of the pericardial contents.
      Sagittal and coronal cross-sections were particularly well-suited to show the non
      uniformity of the pericardial thickening. These results indicate that RNA and MRI
      are complementary non-invasive methods, and can provide the functional and
      anatomical information required for the diagnosis of constrictive pericarditis.

PMID- 8575481
TI  - Regional myocardial blood flow, glucose utilization and contractile function
      before and after revascularization and ultrastructural findings in patients with
      chronic coronary artery disease.
AB  - In patients with chronic coronary artery disease, follow-up measurements of
      myocardial blood flow, metabolism and function were correlated with histology. In
      41 patients with chronic coronary artery disease and a severely stenosed left
      anterior descending coronary artery, a positron emission tomographic (PET)
      flow/metabolism study and nuclear angiography were performed immediately before
      and 3 months after bypass surgery. Biopsies were taken from the left ventricular
      anterior wall at the time of surgery. Control biopsies were taken from donor
      hearts for cardiac transplantation and from hearts of patients with a defect of
      the atrial septum. A significant improvement of flow (P<0.01) and regional
      contractile function (P<0.01) was observed in the mismatch group. Glucose
      utilization was significantly lower (P<0.001) as compared to preoperative values.
      The group with preserved flow and the PET match group revealed no significant
      changes in flow, metabolism or function. Control biopsies revealed significantly
      less myolytic cells as compared to biopsies taken from both match and mismatch
      groups (P<0.01) and less fibrosis as compared to biopsies taken from the match
      group (P<0.01). Postoperatively, linear relationships were found between flow and
      both % fibrosis (r = 0.71, P<0.001) and regional anterior ejection fraction (r =
      0.7, P<0.001). Only mismatch areas revealed significant recovery of both flow and
      function after revascularization with a disappearance of enhanced glucose uptake.
      The better linear correlation between flow and % fibrosis after surgery as
      compared to preoperatively was probably due to improvement of flow values in the
      mismatch group.

PMID- 8575482
TI  - Assessment of myocardial perfusion and viability with technetium-99m
      methoxyisobutylisonitrile and thallium-201 rest redistribution in chronic
      coronary artery disease.
AB  - We compare thallium-201 rest redistribution and fluorine-18 fluorodeoxyglucose
      ([18F]FDG) for the assessment of myocardial viability within technetium-99m
      methoxyisobutylisonitrile (MIBI) perfusion defects in 27 patients with chronic
      stable coronary artery disease. The following studies were performed: (1) stress
      99mTc-MIBI, (2) rest 99mTc-MIBI, (3) 201Tl rest-redistribution single-photon
      emission tomography, (4) [18F]FDG positron emission tomography. The left
      ventricle was devided into 11 segments on matched tomographic images. The segment
      with the highest activity at stress was taken as the reference (activity=100%).
      Perfusion defects at 99mTc-MIBI rest were classified as severe (activity<50%),
      moderate (activity 50%-60%) or mild (activity 60%-85%). Uptakes of [18F]FDG and
      rest-redistributed 201Tl were recognized as significant if they exceeded 50% of
      that in the reference segment. Among the 33 segments with severe 99mTc-MIBI rest
      perfusion defects, 21 had significant [18F]FDG and 10 significant rest
      redistributed 201Tl uptake. As regards the 37 segments with moderate defects,
      [18F]FDG was present in 29 and 201Tl in 31, while of the 134 segments with mild
      defects, 128 showed [18F]FDG uptake, and 131, 201Tl uptake. In conclusion, there
      is an inverse relationship between the severity of 99mTc-MIBI perfusion defects
      and the uptake of rest-redistributed 201Tl and [18F]FDG. Both tracers are
      adequate markers of viability in mild and moderate defects; in severe defects
      201Tl might underestimate the presence of viability as assessed by [18F]FDG.

PMID- 8575483
TI  - An elastic computerized brain atlas for the analysis of clinical PET/SPET data.
AB  - An elastic computerized brain atlas was developed for the analysis of positron
      emission tomography/single-photon emission tomography (PET/SPET) data. It
      consists of a set of digital anatomical contours and a template of regions of
      interest, schematically describing the brain, derived from a currently used
      anatomical/functional brain atlas. A warping algorithm, matching equivalent
      contours, was implemented to elastically fit the atlas to individual brain
      images. The elastic computerized brain atlas was applied to representative
      magnetic resonance imaging (MRI)-PET/SPET studies, MRI providing the anatomical
      information used by the matching procedure. The atlas is suited for clinical use
      in a nuclear medicine environment.

PMID- 8575484
TI  - Gastrointestinal activity following bone marrow scintigraphy with technetium-99m
      nanocolloid in patients with multiple myeloma.
AB  - Unexpected abdominal activity was registered later than 1 h post injection in
      technetium-99m bone marrow scintigrams of 13 multiple myeloma patients and of
      five controls. The activity was considered to be localised in the gastro
      intestinal tract. It is attributed to accumulation of degradation products of the
      used nanocolloid tracer. Corresponding results are known in patients with
      inflammatory bowel disease when scintigraphy is performed with other
      radiopharmaceuticals.

PMID- 8575485
TI  - Pharmacokinetics of an indium-labeled IgG monoclonal antibody over a prolonged
      period.
AB  - This study was directed toward determining the pharmacokinetic fate of an IgG2a
      monoclonal antibody (MoAb). The 96.5 anti-melanoma MoAb was labeled with indium
      111 and indium-114m and administered to BALB/c mice. The mice receiving 111In
      MoAb were sacrificed at 4 and 72 h, while those receiving 114mIn 96.5 MoAb (50
      day physical half-life) were sacrificed at 4 h and 3, 15, and 30 days. Multiple
      tissues were counted against a standard of the injectate and the data expressed
      as percent injected dose per organ and percent total dose excreted in the urine
      and feces. The 111In- and 114mIn-labeled MoAbs had nearly identical distribution
      through 72 h. Over the 30-day period 25% of the 114mIn label was excreted in the
      urine and 50% eliminated in the feces. All of the tissues studied showed a
      decrease in 114mIn in the 30-day period. We conclude that the metabolic products
      of indium-labeled MoAbs, the indium itself, or a combination of both are
      eliminated from the tissues over a period of several weeks and do not accumulate
      to a significant extent in any single site.

PMID- 8575486
TI  - Efficient one-step direct labelling of recombinant antibodies with technetium
      99m.
AB  - High-affinity bacterially expressed antibody fragments can nowadays be cloned
      from established hybridomas or, more conveniently, isolated directly from
      antibody libraries displayed on filamentous phage. Such antibodies can be tagged
      with C-terminal peptide tags containing one cysteine residue, which represents a
      convenient functionalisation site for a number of applications, including
      technetium-99m labelling. Here we describe a simple one-step method for 99mTc
      labelling of cysteine-tagged recombinant antibodies with more than 50%
      radionuclide incorporation. The labelled antibodies displayed full retention of
      immuoreactivity and good stability.

PMID- 8575487
TI  - Clinical utility of technetium-99m methoxisobutylisonitrile imaging in
      differentiated thyroid carcinoma: comparison with thallium-201 and iodine-131 Na
      scintigraphy, and serum thyroglobulin quantitation.
AB  - Recently, technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) has been used to
      image thyroid carcinoma. A prospective study was performed to compare the
      efficacy of 99mTc-MIBI to thallium-201 (201Tl) scintigraphy in patients with
      differentiated thyroid carcinoma. The clinical utility of all radionuclide
      imaging modalities, i.e., 99mTc-MIBI, 201Tl, and iodine-131 Na (131I-Na), as well
      as serum thyroglobulin estimation, was evaluated. Thirty-four post-thyroidectomy
      patients (age range: 26-76 years) underwent 45 studies. Histopathologies studied
      included fourteen papillary, eight papillary-follicular, ten follicular, one
      Hurthle cell, and one medullary carcinoma of the thyroid. Following optimal
      stimulation of endogenous thyroid stimulating hormone (i.e, TSH 50 mU/ml), the
      patients underwent 201Tl and 99mTc-MIBI scintigraphy. Concomitant 131I-Na
      scintigraphy was performed and serum thyroglobulin levels were measured. Sixteen
      scan sets were performed prior to 131I-Na ablation therapy. Twenty-nine scan sets
      were performed following 131I-Na ablation therapy. The presence or absence of
      thyroid cancer was established by clinical, biochemical, radiologic, and/or
      biopsy findings. There was no significant difference in sensitivity and
      specificity of 201Tl scintigraphy versus 99mTc-MIBI scintigraphy in pre- and
      postablation studies. 131I-Na scintigraphy with determination of thyroglobulin
      level was sufficient in preablation studies. Among postablation patients, the
      addition of 99mTc-MIBI or 201Tl offered a higher diagnostic yield. Between the
      201Tl and 99mTc-MIBI studies, there was a concordance of 69% in preablation and
      97% among postablation patients (P=0.027). It is concluded that 99mTc-MIBI is a
      suitable alternative to 201Tl scintigraphy in thyroid carcinoma, especially
      following thyroidectomy and 131I-Na therapy. 131I-Na scintigraphy with serum
      thyroglobulin is adequate in both pre- and postablation patients. Among the post
      131I-Na ablation patients, 99mTc-MIBI or 201Tl is extremely valuable for tumor
      localization, especially when the 131I-Na whole-body scan is negative. The
      combination of 99mTc-MIBI or 201Tl scintigraphy with 131I-Na and serum
      thyroglobulin offers the highest diagnostic yield.

PMID- 8575489
TI  - FDG PET imaging of paragangliomas of the neck: comparison with MIBG SPET.
AB  - Two patients with cervical paragangliomas underwent positron emission tomography
      (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG). There was marked tumor uptake
      and retention of FDG. Adjacent salivary gland accumulation of FDG was minimal,
      though quite prominent with meta-iodobenzylguanidine. FDG PET offers another
      potentially useful approach to functional imaging of these uncommon tumors,
      independent of the presence of specific amine uptake mechanisms or cell surface
      receptors required by other scintigraphic techniques.

PMID- 8575490
TI  - The use of technetium-99m hexamethylpropylene amine oxime labelled granulocytes
      with single-photon emission tomography imaging in the detection and follow-up of
      recurrence of infective endocarditis complicating transvenous endocardial
      pacemaker.
AB  - In this case report we present a patient with a recurrence of subacute bacterial
      infectious endocarditis (IE) complicating a transvenous endocardial pacemaker.
      Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelled
      granulocytes were used for diagnosis and follow-up under medical treatment only,
      since surgical removal of the pacemaker lead was ruled out because of the general
      condition of the patient. Single-photon emission tomography (SPET) imaging
      displayed the active lesion previously suspected on echography. At the end of
      antibiotic therapy, SPET indicated a favourable disease outcome whereas
      echocardiographic abnormalities remained nearly unchanged. The medical treatment
      had eradicated the IE, and the patient did well for more than 1 year thereafter.

PMID- 8575488
TI  - New agents for scintigraphy in rheumatoid arthritis.
AB  - Radiopharmaceuticals have been used as investigative tools for the detection and
      treatment of arthritis activity in rheumatoid arthritis (RA) since the 1950s.
      Against the background of the pathophysiology of RA, the current status of joint
      scintigraphy and possible future developments are reviewed. Both non-specific
      (radiolabelled leucocytes and technetium-99m labelled human immunoglobulin) and
      specific targeting radiopharmaceuticals (including radiolabelled antibodies) are
      considered. The use of radiopharmaceuticals in the detection of arthritis
      activity has the advantages of allowing direct imaging of joints by means of
      whole-body scintigraphy and of joints that are difficult to assess clinically or
      radiographically. Promising results have been obtained with radiolabelled anti
      CD4 and anti-E-selectin antibodies and with somatostatin receptor imaging, but
      more data are available regarding 99mTc-IgG scintigraphy, which differentiates
      between the various degrees of arthritis activity and thus facilitates the choice
      of antirheumatic drug. Newer promising approaches to the imaging of RA include
      the use of radiolabelled J001 and cytokines, though studies on these are limited
      at present.

PMID- 8575491
TI  - Administration of potassium perchlorate to improve the quality of gated blood
      pool imaging.

PMID- 8575492
TI  - The role of adjuvant treatment in low-stage germ cell testicular tumors.
AB  - OBJECTIVE: To find out up-to-date indications to adjuvant therapy in low-stage
      germ cell tumors (GCT) of the testis. METHODS: The authors reviewed the material
      of the National Cancer Institute in Milan and the major international papers on
      adjuvant therapies of GCT of the testis. RESULTS: Moderate dose irradiation of
      retroperitoneal nodes remains the standard therapy of stage I seminoma;
      mediastinal irradiation has been abandoned in stage II seminoma. Nerve-sparing
      retroperitoneal lymph node dissection and surveillance remain standard therapies
      for nonseminomatous stage I tumors; 2 adjuvant courses of cisplatin-based
      chemotherapy are under investigation in high-risk patients. Postoperative
      adjuvant chemotherapy is mandatory only in bulky pathological stage II non
      seminoma, but it is advisable also in patients who cannot be carefully followed.
      CONCLUSION: The cure rates of GCT of the testis can approach 100% in low stages
      and similar results can be achieved with different treatment modalities, but the
      maximum results can be obtained in specialized centers only.

PMID- 8575493
TI  - The final analysis of the EORTC Genito-Urinary Tract Cancer Co-Operative Group
      phase III clinical trial (protocol 30805) comparing orchidectomy, orchidectomy
      plus cyproterone acetate and low dose stilboestrol in the management of
      metastatic carcinoma of the prostate.
AB  - This report is the final analysis of an EORTC Genito-Urinary Group Phase III
      trial (Protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone
      acetate 50 mg 3 times a day and stilboestrol 1 mg daily in the management of
      metastatic carcinoma of the prostate. Three hundred and twenty-eight eligible
      patients admitted into the study have been followed up for a median period of 4
      years. There was no difference in time to metastatic progression and overall
      survival between the treatment arms. The cardiovascular toxicity of stilboestrol
      1 mg daily has resulted in more cardiovascular deaths as compared with the
      orchidectomy treatment arm. The outcome for individual patients has been
      determined by on-study prognostic factors, especially the performance status,
      rather than the treatment given.

PMID- 8575494
TI  - Adjuvant treatment with a vitamin A analogue (etretinate) after transurethral
      resection of superficial bladder tumors. Final analysis of a prospective,
      randomized multicenter trial in Switzerland.
AB  - Vitamin A and its derivatives, the retinoids, have antiproliferative effects and
      may induce cellular differentiation. Etretinate, a synthetic retinoid, has a more
      favorable therapeutic index experimentally than all-trans-retinoic acid or 13-cis
      retinoic acid. Ninety patients with superficial papillary bladder tumors stages
      Ta and T1 entered a prospective randomized double-blind multicenter trial in
      Switzerland. Seventy-nine of the patients were eligible and received either 25 mg
      of etretinate or a placebo orally each day. The early withdrawal of a
      significantly greater number of patients in the placebo group for treatment
      failure during the first year of the study resulted in a secondary positive
      selection in this group. High-risk patients were removed and low-risk patients
      remained. In those patients who had tumor recurrences after randomization, the
      time to first recurrence was similar in both groups with 13.5 and 13.6 months in
      the placebo and etretinate groups, respectively. However, the mean interval to
      subsequent tumor recurrence was significantly longer in the etretinate group. The
      mean interval between recurrences in these subgroups was 12.7 months in the
      placebo arm and 20.3 months in the etretinate arm (p = 0.006). Consequently, the
      number of transurethral resections per patient-year was also reduced
      significantly in the etretinate group (p < 0.001). In patients with more than one
      transurethral resection of papillary tumors before randomization, the annual
      transurethral resection rate in the two treatment groups dropped from 1.7 to 1.3
      in the 30 patients in the placebo group (NS, p = 0.1) and from 2.1 to 0.95 in the
      25 patients in the etretinate group (p < 0.001). The side effects of etretinate
      (cheilitis, dryness of mucous membranes and skin) were acceptable to most
      patients. The relationship of the 3 myocardial infarcts observed in the
      etretinate group to the retinoid is not clear. Despite their significant effect
      on the recurrence rate of superficial papillary bladder tumors, retinoids should
      only be used in well-controlled prospective trials until more is known about
      their dosage-toxicity profiles.

PMID- 8575495
TI  - Comparison of two doses of interferon-alpha-2b in intravesical prophylaxis of
      superficial bladder tumors. Portuguese Genito-Urinary Group.
AB  - The purpose of the study was to compare two doses of interferon-alpha 2b (60 and
      100 million units, MU) and to define the recurrence rate per year, tumor rate per
      year and the toxicity for both treatment arms. 127 patients were admitted to the
      study and randomized between the two treatments: 64 patients in the 60-MU regimen
      (28 single primary, 8 multiple primary, 28 recurrent), and 63 patients (22 single
      primary, 10 multiple primary, 31 recurrent) in the 100-MU regimen. Of the 64
      patients receiving 60 MU, 26 patients had recurrences (33 recurrences with a
      follow-up of 2,478 months). Of the 63 patients receiving 100 MU, 21 patients had
      recurrences (26 recurrences with a follow-up of 2,329 months). The recurrence
      rate per year for 60 MU is 0.13 and 0.11 for 100 MU and the tumor rate per year
      is 0.34 and 0.36, respectively. In conclusion the quality of life of the patients
      is very good with no side effects, and, using Fisher's exact test for statistical
      comparison, there was no difference in the recurrence rate per year and the tumor
      rate per year between the 2 groups.

PMID- 8575496
TI  - Local immunotherapy of superficial bladder cancer by intravesical instillation of
      recombinant interleukin-2.
AB  - Local immunotherapy of superficial bladder cancer by endovesical administration
      of recombinant interleukin-2 (rIL-2) was investigated in a phase I-II study.
      Twenty-five patients with Ta-T1, N0, M0, G1-G2 transitional cell carcinoma of the
      bladder received an induction course of rIL-2 (10 daily instillations) with the
      tumor in place using an interpatient dose escalation scheme from 3 to 18 x 10(6)
      IU/day. Seven to fourteen days after the end of the induction course, the
      objective clinical response was evaluated and transurethral resection of the
      bladder tumor was carried out. Four maintenance courses (10 daily instillations)
      were started 1 month after surgery and carried out every 4 months at a dose of 6
      x 10(6) IU/day in all patients. Follow-up visits were scheduled bimonthly during
      treatment and then every 6 months. No evidence of laboratory, local or systemic
      toxicity was observed even at the highest rIL-2 dosages. Induction of a local
      inflammatory response could be demonstrated at the tumor site after intravesical
      rIL-2 treatment. The significant reduction in tumor diameters observed in some
      patients may be interpreted as a sign of the biological activity of this rIL-2
      regimen. Further exploratory work is required to evaluate the clinical efficacy
      of this immunotherapeutic approach.

PMID- 8575497
TI  - Proscar: five-year experience.
AB  - We assessed the long-term safety and efficacy of finasteride, an orally active 5
      alpha-reductase inhibitor, in 2 previously reported groups of patients with
      symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by
      magnetic resonance imaging, and the maximum urinary flow rate was assessed
      noninvasively. Symptoms were scored utilizing a patient self-administered symptom
      score questionnaire. Total symptom scores ranged from 0 (or asymptomatic) to 35
      (severely symptomatic). After an initial double-blind period, the patients in
      study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg
      finasteride for an additional 4 years, whereas patients in study 2 were treated
      with 5 mg finasteride for the entire 5 years. A total of 190 patients were
      randomized in the double-blind studies, 156 entered year 1 of the open extension
      and 70 patients completed 5 years of finasteride therapy. In both studies
      prostate volume was reduced from baseline by 30%, dihydrotestosterone was reduced
      by 72%, and the maximum urinary flow rate improved by approximately 1.5 ml/s.
      Prostate-specific antigen was decreased by approximately 50%. Finasteride was
      well tolerated; approximately 10% of patients reported sexual adverse experiences
      during the 5-year study period, which were considered drug related by the
      investigators. The incidence in reporting sexual adverse experiences did not
      increase with the increased duration of treatment: findings consistent with
      previous reports. In summary treatment of BPH with finasteride for 5 years
      inhibits the progression of the disease with an excellent safety profile and
      represents a low-risk medical option for the treatment of symptomatic BPH.

PMID- 8575498
TI  - Surgical management of renal cell cancer with extension into the vena cava:
      usefulness of intra-operative sonography.
AB  - Intracaval tumour extension represents a significant surgical problem in patients
      with renal cell carcinoma. Although pre-operative imaging techniques provide
      sufficient visualization for the planning of the majority of operative
      procedures, intra-operative ultrasound is nonetheless beneficial in some cases.
      In 3 patients, the procedure has given an accurate evaluation of the extent of
      the tumour thrombus. It has allowed safe placement of instruments which had
      lessened the risk of thrombus dislodgement. Intra-operative sonography is simple
      to perform and can be considered a valuable new adjunct in the evaluation and
      management of renal cell carcinoma with intracaval tumour extension. New
      technological advances may eventually improve the quality of intra-operative
      imaging.

PMID- 8575499
TI  - Penile sympathic skin response in erectile dysfunction.
AB  - Penile sympathic skin response (PSSR) was measured in 20 normal patients and in
      46 patients with erectile dysfunction (ED). PSSR could be registered in 80% of
      normal patients. The latencies were 1,100-1,600 ms. In patients with ED,
      latencies were 1,240-3,640 ms. A reproducible normal latency of PSSR (< 1,600 ms)
      indicates a normal sympathic innervation of the penis. Long latencies (> 1,800
      ms) indicate neuropathy of unmyelinated nerval fibers. The loss of a reproducible
      answer however allows no exact diagnostic information. PSSR is a useful
      diagnostic test for detecting neuropathy of unmyelinated nerval fibers as a
      possible cause of ED.

PMID- 8575500
TI  - Minimal invasive therapy of prostatic abscess by transrectal ultrasound-guided
      perineal drainage.
AB  - Prostatic abscess is a rare but severe disease. Conventional therapy is
      transurethral resection of the prostatic abscess. Since the advent of transrectal
      ultrasound (TRUS) a minimal-invasive treatment of prostatic abscess by TRUS
      guided perineal drainage under local anesthesia is available. We report on our
      experience in 6 patients with prostatic abscess. TRUS is a simple, rapid, easily
      accessible, and accurate method for diagnosis, therapy and follow-up of a
      prostatic abscess. TRUS-guided perineal drainage of a prostatic abscess is an
      effective, minimal-invasive and cost-effective treatment without adverse side
      effects.

PMID- 8575501
TI  - Prolonged bladder distension: experience in the treatment of detrusor
      overactivity and interstitial cystitis.
AB  - Prolonged bladder distension continues to be recommended for the treatment of
      detrusor instability and other bladder conditions. We have reviewed our
      experience of the technique. A total of 45 patients have undergone 50 procedures.
      Only 1 of 29 patients with detrusor instability had sustained improvement. 6 of 7
      patients with interstitial cystitis noted improvement, sustained in 3. All the
      other patients noted some improvement. There was a 20% complication rate. 33
      (75%) of the living patients returned questionnaires with 27% feeling that the
      operation was worthwhile. We feel that prolonged distension of the bladder is
      unhelpful in the treatment of patients with detrusor instability. Its place in
      the management of patients with interstitial cystitis and irritative symptoms
      remains controversial. The place of simple bladder distension should be
      considered.

PMID- 8575502
TI  - Videoendoscopic cutaneous ureterostomy for palliative urinary diversion in
      advanced pelvic cancer.
AB  - Since January 1993, 9 patients with bilateral ureteral obstruction due to
      advanced pelvic cancers underwent videoendosurgical cutaneous ureterostomy. Five
      patients had prostate cancer, 3 had uterine cancer and only 1 bladder cancer. In
      5 cases a bilateral laparoscopic transperitoneal procedure was performed. In 4
      cases a retroperitoneal laparoscopic technique was adopted and only in 1 out of
      these 4 cases the procedure was done bilaterally. All the procedures were done
      under general anesthesia. The procedure was accomplished in all the cases without
      any intraoperative complication; the operative time ranged between 35 and 130
      min. Postoperative pain was rather insignificant and did not require additional
      medication. Postdiversion hospital stay ranged from 3 to 11 days according to the
      general condition of the patients. The mean follow-up is 10.8 months. In
      conclusion, retroperitoneal laparoscopic cutaneous ureterostomy seems to be a
      reasonable alternative to percutaneous nephrostomy in case of bilateral ureteral
      obstruction due to advanced prostate or uterine cancer, provided that the
      clinical condition of the patient allows general anesthesia.

PMID- 8575503
TI  - Urinary interleukin-1 alpha levels are increased by intravesical instillation
      with keyhole limpet hemocyanin in patients with superficial transitional cell
      carcinoma of the bladder.
AB  - Intravesical instillation of keyhole limpet hemocyanin (KLH) is a possible
      treatment for decreasing tumor recurrence after transurethral resection (TUR) in
      patients with superficial transitional cell carcinoma of the bladder (stages pTa
      pT1, grades 1-3). Our study confirms the theory that instillation of KLH
      stimulates production of cytokines, resulting in their secretion in urine.
      Interleukin-1 (IL-1) stimulates the immune cascade through a domino effect and is
      produced mainly by activated macrophages. The instillation program was started 5
      7 days after TUR of primary superficial cell carcinoma. 20 mg KLH in 20 ml of
      0.9% NaCl was instilled into the bladder each week for 6 consecutive weeks and
      then monthly for 1 year. When KLH is instilled into the bladder, IL-1 alpha is
      secreted in the urine. A specific enzyme-linked immunosorbent assay (ELISA) was
      used for analysis. The ELISA for IL-1 alpha was established in our laboratory and
      showed a detection limit of 5 pg/ml. This IL-1 alpha ELISA deviation amounts to 3
      7% within a series of measurements, and 5-15% from series to series. In the
      therapy group the IL-1 alpha secretion ranged from 0 to 30,905 pg/24 h and in the
      control group from 0 (collection period) to 2,472 pg/4 h. IL-1 alpha production
      increased significantly after KLH instillation in bladder cancer patients;
      however, the level varied considerably from patient to patient. Maximum
      production was achieved within a period of 4-8 h, decreasing within 24 h. There
      was a striking difference between the amount of IL-1 alpha produced over the 24
      hour period in the control group and that of the KLH group. 8 of 14 patients
      (57%) who responded to KLH therapy had higher urine IL-1 alpha levels after 6
      weeks of KLH treatment than those who failed to respond within 12 months, but the
      levels were not of statistical significance. The secretion of IL-1 alpha in urine
      is the biological response of the bladder to the antigen stimulus of KLH. No IL-2
      was detected in the urine samples. It remains to be determined whether no IL-2
      cytokine was present, or whether the amount was smaller than the minimal
      detection limit required for the ELISA.

PMID- 8575504
TI  - Intravesical application of oxybutynine: mode of action in controlling detrusor
      hyperreflexia. Preliminary results.
AB  - Topical oxybutynine (Oxy) has been used successfully in neurogenic bladder
      patients who remained wet on oral anticholinergics or could not tolerate oral
      medication. However, little is known about the pharmacokinetics of intravesical
      Oxy. The aim of this study was to evaluate the resorption rate of intravesically
      given Oxy in the bladder in comparison with oral intake, and to find out which
      pharmacological properties of the drug are responsible for its effect when given
      intravesically. Our results indicate that peak plasma levels of intravesical Oxy
      appear later, are lower and stay longer compared to oral intake. Cystometries
      before, 20 min and 2 h after intravesical application of Oxy indicate that the
      main effect of intravesical Oxy on the detrusor is systemic due to its
      resorption. Our findings confirm the clinical experience that intravesical Oxy is
      well tolerated, very efficacious and better than oral medication.

PMID- 8575505
TI  - Mixed adenocarcinoma and neuroendocrine carcinoma arising in the urachus. A case
      report and review of the literature.
AB  - Primary urachal carcinomas are very rare urological malignancies. In the present
      article we report an unusual case of a small cell carcinoma with neurendocrine
      features and adenocarcinoma arising in the urachus, and review the literature.
      The results of the immunohistochemical studies are presented.

PMID- 8575506
TI  - Concerning the article by Terasaki T, Watanabe H, et al. Eur Urol 1995;27:280
      285. Magnetic resonance angiography in prostatodynia.

PMID- 8575507
TI  - Spatial memory deficits following stimulation of hippocampal 5-HT1B receptors in
      the rat.
AB  - In this study we examined a possible contribution of serotonin (5
      hydroxytryptamine, 5-HT) to spatial memory performance in the rat. Rats were
      trained to run in a radial maze in a manner that involved two kinds of memory
      function, i.e. working memory and reference memory. They received
      intrahippocampal microinjections of a 5-HT1A [8-hydroxy-2-(di-n
      propylamino)tetralin or 8-OH-DPAT], or a 5-HT1B [3-(1,2,5,6-tetrahydropyrid-4
      yl)pyrrolo[3,2-b]pyrid-5-one or CP-93,129] receptor agonist, and a muscarinic
      receptor antagonist (scopolamine). 8-OH-DPAT (5 micrograms/microliters), like
      injections of saline, induced no change in performance levels. In contrast, rats
      suffered an impairment in both reference and working memory following injection
      of scopolamine (10 micrograms/microliters). CP-93,129 induced a higher frequency
      of reference memory errors than of working memory errors at the intermediate (10
      micrograms/microliters) and higher doses (16 micrograms/microliters). Thus, the
      stimulation of 5-HT1B receptors in the CA1 field of the dorsal hippocampus
      impairs the performance of rats in a spatial learning task.

PMID- 8575508
TI  - Lack of selectivity for ventricular and ischaemic tissue limits the
      antiarrhythmic actions of lidocaine, quinidine and flecainide against ischaemia
      induced arrhythmias.
AB  - The antiarrhythmic effectiveness, electrocardiographic and haemodynamic
      properties of three representative class I antiarrhythmics have been investigated
      in anaesthetized rats. Quinidine, lidocaine and flecainide were chosen as
      representatives of class Ia, Ib and Ic, respectively. Lidocaine showed the
      greatest frequency and 'ischaemia' dependency and a high dose provided complete
      protection against ischaemic arrhythmias induced by coronary artery occlusion.
      Flecainide showed the least frequency and ischaemia dependency and the least
      antiarrhythmic effectiveness. Quinidine was only slightly more effective than
      flecainide. The three drugs were approximately equi-potent in lowering blood
      pressure which limited the maximum dose that could be tested. The highest dose of
      lidocaine also caused convulsions in conscious animals. Thus, while lidocaine had
      selectivity for ischaemic tissue, and for high frequencies, the central nervous
      system and cardiovascular toxicity limited its usefulness against ischaemia
      induced arrhythmias. Quinidine and flecainide's lack of selectivity for
      ischaemia, and/or high frequencies, probably accounted for their limited
      antiarrhythmic actions against ischaemia-induced arrhythmias. This study
      emphasizes that class I drugs can only provide useful protection against
      ischaemia-induced arrhythmias if they have marked cardiac selectivity as well as
      selectivity for ischaemic cardiac tissue.

PMID- 8575509
TI  - Effect of alpha 2-adrenergic drugs dexmedetomidine and atipamezole on
      extracellular amino acid levels in vivo.
AB  - alpha 2-Adrenoceptors are known to be involved in a variety of physiological
      functions and pathological conditions, including epilepsy and the extent of
      excitotoxin-induced cell death. In this study we evaluated whether selective
      alpha 2-adrenergic drugs can modulate the release of neurotransmitter amino
      acids. The effect of the alpha 2-adrenoceptor agonist dexmedetomidine (5
      micrograms/kg, s.c.) and the alpha 2-adrenoceptor antagonist atipamezole (0.1
      mg/kg and 1 mg/kg, s.c.) on the release of extracellular glutamate, aspartate and
      gamma-aminobutyric acid (GABA) was studied with microdialysis in the hippocampus
      of freely moving rats under basal and K(+)-evoked conditions. Atipamezole (1
      mg/kg) decreased K(+)-evoked glutamate efflux by 30% compared to the control
      group (P < 0.05) but did not affect significantly the effluxes of aspartate and
      GABA. Dexmedetomidine and the lower dose of atipamezole (0.1 mg/kg) did not
      significantly alter the evoked overflow of amino acids. The results suggest that
      alpha 2-adrenergic drugs have only modest effects on the K(+)-stimulated overflow
      of extracellular neurotransmitter amino acids in rat hippocampus.

PMID- 8575510
TI  - Heterogeneous endothelin receptors mediate relaxation and contraction in the
      guinea-pig ileum.
AB  - IRL1620, a specific endothelin ETB receptor agonist, induced relaxation followed
      by contraction in the guinea-pig ileum, as did endothelin-1. Both components of
      the response were concentration-dependent in the range studied. Repeated
      administration of IRL1620 induced tachyphylaxis only of the contractile
      component, whereas endothelin-1 desensitized both components. BQ-123 (cyclo[D-Trp
      D-Asp-Pro-D-Val-Leu]), a specific endothelin ETA receptor antagonist, did not
      inhibit the relaxation induced by either agonist, although it did inhibit the
      contraction induced by endothelin-1, but not by IRL1620. PD145065 (Ac-(D-Bhg-Leu
      Asp-Ile-Ile-Trp) (D-Bhg = 5H-dibenzyl[a,d]cycloheptene-10,11-dihydroglycine)), a
      combined endothelin ETA/endothelin ETB receptor antagonist, inhibited the
      contractile effects of both endothelin-1 and IRL1620 and also inhibited the
      relaxation induced by IRL1620. Apamin, a Ca(2+)-activated K+ channel blocker,
      inhibited only the endothelin-1-induced relaxation. Our studies suggest that two
      endothelin ETB receptor subtypes mediate relaxation in the guinea-pig ileum: one
      is less sensitive to PD145065 but apamin-inhibitable, and the other is more
      sensitive to PD145065 but not apamin-inhibitable. Our results also suggest that
      both endothelin ETA and endothelin ETB receptor subtypes mediate contraction in
      the ileum.

PMID- 8575511
TI  - Effects of a selective alpha 2-adrenoceptor antagonist, atipamezole, on
      hypothalamic histamine and noradrenaline release in vivo.
AB  - In vivo microdialysis was used to study the effects of a potent and selective
      alpha 2-adrenoceptor antagonist, atipamezole, on histamine and noradrenaline
      release from the medial hypothalamus in anesthetized rats. Local perfusion with
      atipamezole via the microdialysis probe increased histamine release significantly
      and dose-dependently. However, the effect of systemic administration of
      atipamezole (1 mg/kg) was opposite: it significantly decreased histamine release.
      Local and systemic administration of atipamezole produced an approx. 2-fold
      increase in noradrenaline release. To study the modulatory effect of
      noradrenergic neurons on histamine release, noradrenaline synthesis was inhibited
      with alpha-methyl-p-tyrosine. In the microdialysis experiment, rats that received
      alpha-methyl-p-tyrosine exhibited no decrease, but rather a slight increase in
      histamine release in response to systemic atipamezole administration. These
      results show clearly that atipamezole enhances noradrenaline release in vivo from
      rat hypothalamus and its effects on histamine release are dependent on the route
      of drug administration.

PMID- 8575512
TI  - Action of dexmedetomidine on rat locus coeruleus neurones: intracellular
      recording in vitro.
AB  - The action of dexmedetomidine on rat locus coeruleus neurones was examined using
      intracellular recordings from the in vitro brain slice preparation.
      Concentrations of dexmedetomidine from 1 to 1000 nM were tested. At 30 nM,
      dexmedetomidine produced complete inhibition of firing of all neurones tested (n
      = 21); this was associated with a 13 mV hyperpolarization (range 2.2-29.7 mV, n =
      21) and a 27% reduction in input resistance (range 11.1-46.2%, n = 17). The
      dexmedetomidine responses reached a plateau phase between 100 and 1000 nM. Based
      on single-cell recordings, the hyperpolarizing potency of dexmedetomidine was
      found to be 6 times greater than that of clonidine (n = 10). The reversal
      potential for the dexmedetomidine-induced hyperpolarization was -106.9 +/- 1.7 mV
      (n = 9), a value similar to the K+ equilibrium potential; hyperpolarization was
      blocked by both CsCl and BaCl2. The effect of dexmedetomidine was antagonized by
      yohimbine, with a dissociation equilibrium constant of 30 nM. In contrast,
      prazosin, the alpha 1-, alpha 2B- and alpha 2C-adrenoceptor subtype-preferring
      ligand, did not inhibit the dexmedetomidine effect. Our results also show that
      low concentrations of oxymetazoline (10-300 nM), an alpha 2A-adrenoceptor subtype
      selective drug, cause profound inhibition of neuronal activity in the locus
      coeruleus. These data therefore suggest that dexmedetomidine binds to alpha 2A
      adrenoceptors on the cell membrane of neurones of the locus coeruleus and that
      this leads to opening of the inwardly rectifying K+ channels, resulting in the
      observed hyperpolarization of the membrane.

PMID- 8575513
TI  - Inhibition of non-adrenergic non-cholinergic relaxations by nitric oxide donors.
AB  - The effects of pretreatment with the nitric oxide (NO)-releasing substances 3
      morpholino-sydnoninime (SIN-1) and nitroglycerin were investigated on relaxations
      induced by non-adrenergic non-cholinergic (NANC) nerve stimulation, authentic NO
      and vasoactive intestinal polypeptide (VIP) in the rat gastric fundus. Short
      periods of electrical stimulation (0.5-16 Hz, 1 ms, pulse trains of 10 s) induced
      frequency-dependent transient relaxations, previously shown to be mainly mediated
      by NO. Both SIN-1 (10-100 microM) and nitroglycerin (0.5 mM) pretreatment
      significantly reduced these electrically induced responses to a similar extent as
      the inhibitor of the NO biosynthesis L-nitroarginine (30-300 microM). Prolonged
      periods of electrical stimulation (16 Hz, 1 ms, pulse trains of 180 s) induced a
      sustained relaxation, previously shown to be mediated by NO and VIP. L
      Nitroarginine (30-300 microM) or pretreatment with SIN-1 (100 microM) or
      nitroglycerin (0.5 mM) did not affect the amplitude of this relaxation but slowed
      down its onset. Authentic NO (0.01-10 microM) and VIP (0.01-10 nM) induced
      respectively transient and sustained concentration-dependent relaxations. SIN-1
      or nitroglycerin pretreatment had no effect on the concentration-response curves
      to NO and VIP. These results indicate that prolonged exposure to NO donors
      inhibits electrically induced nerve-mediated NANC relaxations without affecting
      the postjunctional response to NO and VIP. As similar results are obtained with
      NO biosynthesis inhibitors, our results illustrate a prejunctional inhibitory
      effect of NO on the NANC nerves of the rat gastric fundus and suggest the
      presence of an autoregulatory mechanism for the nitrergic innervation.

PMID- 8575514
TI  - The effects of formoterol, a long-acting beta 2-adrenoceptor agonist, on
      mucociliary activity.
AB  - The effect on mucociliary function of formoterol, a beta 2-adrenoceptor agonist
      bronchodilator with a prolonged duration of action (as compared with salbutamol
      or terbutaline), was investigated both in vitro and in vivo with a photoelectric
      technique. Formoterol, and its (R,R)-enantiomer, increased ciliary beat frequency
      in vitro in guinea pig trachea preparations (peak increase 17.2 +/- 2.0% at a
      concentration of 10(-7) M) and in vivo in the rabbit maxillary sinus (peak
      increase 23.0 +/- 4.0% at a dosage of 1 nmol/kg). Formoterol was approximately
      100 times more potent than terbutaline in vitro, as judged from the dose-response
      curve. The main difference between their effect in vivo was the 2-fold longer
      duration of the mucociliary acceleration after formoterol at 1 nmol/kg than after
      terbutaline at the equi-effective dosage of 10 nmol/kg terbutaline (20 vs. 10
      min, respectively). The findings indicate formoterol to be a powerful, long
      acting ciliostimulant, a property which may be of clinical advantage in the
      treatment of airway disease.

PMID- 8575515
TI  - Effects of marine 2-polyprenyl-1,4-hydroquinones on phospholipase A2 activity and
      some inflammatory responses.
AB  - Three 2-polyprenyl-1,4-hydroquinone derivatives (2-heptaprenyl-1,4-hydroquinone:
      IS1, 2-octaprenyl-1,4-hydroquinone: IS2 and 2-[24-hydroxy]-octaprenyl-1,4
      hydroquinone: IS3) isolated from the Mediterranean sponge Ircinia spinosula, were
      evaluated for effects on phospholipase A2 activity of different origin (Naja naja
      venom, human recombinant synovial fluid and bee venom), as well as on human
      neutrophil function and mouse ear oedema induced by 12-O-tetradecanoylphorbol 13
      acetate (TPA). IS1 interacted minimally with these responses. In contrast, IS2
      and IS3 inhibited human recombinant synovial phospholipase A2 in a concentration
      dependent manner, with minor effects on the rest of the enzymes. Both compounds
      slightly affected superoxide generation and degranulation in human neutrophils,
      whereas they decreased thromboxane B2 and leukotriene B4 synthesis and release in
      a mixed suspension of human platelets and neutrophils stimulated by ionophore
      A23187, with IC50 values in the microM range. IS3 was the most effective
      inhibitor of the synthesis of thromboxane B2 by human platelet microsomes and of
      leukotriene B4 by high speed supernatants from human neutrophils. IS2 and IS3
      showed topical anti-inflammatory activity against the TPA-induced ear
      inflammation in mice, with similar effects on oedema and a higher inhibition of
      IS3 on leukocyte migration, estimated as myeloperoxidase activity in supernatants
      of ear homogenates. Some structure-activity relationships were established since
      differences in the prenylated chain attached to the hydroquinone moiety result in
      important modifications of these inflammatory responses.

PMID- 8575516
TI  - Differentiation of in vivo effects of AMPA and NMDA receptor ligands using drug
      discrimination methods and convulsant/anticonvulsant activity.
AB  - The discriminative stimulus properties of the AMPA ((RS)-2-amino-3-(3-hydroxy-5
      methylisoxazol-4-yl)propionic acid) receptor agonist ATPA ((RS)-2-amino-3-(3
      hydroxy-5-tert-butylisoxazol-4-yl)propionic acid) and NMDA (N-methyl-D-aspartic
      acid) in rats have been characterized. It is suggested that the cues are mediated
      by separate mechanisms in the central nervous system. The ATPA cue is not
      mimicked by NMDA or an NMDA receptor agonist, and is inhibited by the AMPA
      receptor antagonist (R)-APPA ((R)-2-amino-3-(3-hydroxy-5-phenylisoxazol-4
      yl)propionic acid) but not the AMPA receptor antagonist ATOA ((RS)-2-amino-3-(3
      carboxymethoxy-5-tert-butylisoxazol-4-yl)propio nic acid) or the NMDA receptor
      antagonist CPP ((RS)-3-(2-carboxypiperazin-4-yl)propyl)phosphonic acid). The ATPA
      cue is not mimicked by AMPA which is believed not to penetrate the blood-brain
      barrier. In contrast, ATPA does not generalize to the NMDA cue, which is mimicked
      by some NMDA receptor agonists (tetrazol-5-yl-glycine and AMAA ((RS)-2-amino-2-(3
      hydroxy-5-methylisoxazol-4-yl)acetic acid)) and is inhibited by the NMDA receptor
      antagonist CPP. Highly potent convulsant activity was demonstrated in mice with
      all AMPA and NMDA receptor agonists after intracerebroventricular (i.c.v.)
      injection, whereas weaker or no effects were found after subcutaneous (s.c.) or
      intravenous injection. Only (RS)-tetrazol-5-yl-glycine had a potent effect after
      s.c. administration. I.c.v. ATOA and CPP inhibited convulsions induced by i.c.v.
      injection of AMPA or NMDA, while (R)-APPA was ineffective. These results indicate
      that there are differences in the structure-activity relations in the drug
      discrimination and convulsant/anticonvulsant models, even when effects after
      i.c.v. and s.c. injection are taken into consideration. The convulsion models are
      rapid tests which can give an indication of central nervous system penetration,
      but are less pharmacologically specific with respect to differentiation between
      AMPA and NMDA ligands where cue models demonstrate clear differences in effects
      of ligands with selectivity for receptor subtypes.

PMID- 8575517
TI  - Evidence against the involvement of the nucleus tractus solitarii in the
      sympatholytic effect of 8-hydroxy-2-(di-n-propylamino)tetralin in the cat.
AB  - In different animal species, microinjections of the 5-HT1A receptor agonist 8
      hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the nucleus tractus
      solitarii failed to alter arterial blood pressure and sympathetic nerve activity;
      however, the cardiovascular effects (hypotension, bradycardia, reduction in
      sympathetic nerve activity) of intravenous administration of 8-OH-DPAT were
      significantly reduced after blockade of the nucleus tractus solitarii by kainic
      acid as well as after blockade of the lateral tegmental field by kainic acid. The
      aim of the present study was to clarify these conflicting results. In the
      anesthetized cat, inhibition of neurotransmission in the nucleus tractus
      solitarii by bilateral microinjections of either muscimol (1 nmol in 50 nl) or
      kynurenic acid (2.5 nmol in 50 nl) suppressed the baroreceptor reflex and
      abolished the synchronism between the renal sympathetic bursts; however, these
      procedures did not alter the dose-related hypotension, bradycardia and sympatho
      inhibition elicited by cumulative doses of 8-OH-DPAT (1-30 micrograms/kg i.v.).
      Moreover complete electrolytic destruction of the nucleus tractus solitarii,
      assessed by a complete loss of the baroreceptor reflex and the cardiac-related
      bursts of the sympathetic nerves, failed to alter the inhibitory effects of i.v.
      8-OH-DPAT. Bilateral microinjections of muscimol into the lateral tegmental field
      induced a decrease of mean arterial blood pressure, heart rate and renal nerve
      activity (by respectively -35 +/- 13 mm Hg, -30 +/- 16 beats/min and -53 +/- 14%)
      and greatly reduced the effects of subsequent i.v. administration of 8-OH-DPAT.
      The present data indicate that the nucleus tractus solitarii does not play a
      dominant role in the central action of 8-OH-DPAT whereas they confirm our
      previous results showing that the lateral tegmental field is involved in this
      action and in the mecanisms regulating sympathetic tone. The results also suggest
      that kainic acid lesions are not restricted to the region in which the neurotoxic
      agent is injected.

PMID- 8575518
TI  - Potentiation of phencyclidine-induced dopamine release in the rat striatum by the
      blockade of dopamine D2 receptor.
AB  - Local perfusion with phencyclidine (PCP) increased extracellular dopamine levels
      in the rat striatum in a dose-dependent manner, as measured by in vivo
      microdialysis. While pretreatment with SCH 23390, a selective dopamine D1
      receptor antagonist, had no significant effect on PCP-induced increases in
      extracellular dopamine levels, pretreatment with YM-09151-2 (cis-N-(1- benzyl-2
      methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylamin obenzamide), a selective
      dopamine D2 receptor antagonist, markedly potentiated the effect of PCP. These
      results suggest that the blockade of dopamine D2 presynaptic autoreceptors
      strongly potentiates the PCP-induced dopamine release in the striatum.

PMID- 8575519
TI  - Imidazoline compounds inhibit KATP channels in guinea pig ventricular myocytes.
AB  - Phentolamine and related imidazolines inhibit KATP channel activity in the
      pancreatic beta cell. In the present study, the effects of several imidazoline
      based compounds were examined upon KATP channel activity in guinea pig
      ventricular myocytes. Phentolamine produced a potent inhibition of KATP channel
      activity when examined in either excised inside-out patches or in the whole-cell
      configuration. This effect was unrelated to phentolamine's ability to antagonise
      alpha-adrenoceptors since the nonselective alpha-adrenoceptor antagonists,
      benextramine and phenoxybenzamine, failed to affect channel activity.
      Furthermore, the alpha-adrenoceptor agonist clonidine together with several
      related imidazolines inhibited channel activity. This suggests that imidazoline
      compounds modulate KATP channel activity in guinea pig ventricular myocytes and
      this may have clinical implications for the use of such agents as hypoglycemic
      drugs.

PMID- 8575520
TI  - Evidence for a 5-HT1D receptor-mediated hypothermic effect of the alpha 1
      adrenoceptor agonist, SDZ NVI-085, in guinea-pigs.
AB  - The alpha 1-adrenoceptor agonist, SDZ NVI-085 ((-)-(4aR,10aR)-3,4,4a,5,10,10a
      hexahydro-6-methoxy-4- methyl-9-(methylthio)-2H-naphth[2,3-b]-1,4-oxazine.HCl; 1
      mg/kg i.p.), decreased body temperature of guinea-pigs. Two 5-HT1D receptor
      antagonists, GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl
      4'-(5-methyl- 1,2,4-oxadiazol-3yl)[1,1-biphenyl]-4-carboxamide) and PAPP (p
      aminophenylethyl-m-trifluoromethylphenyl piperazine; both compounds at 1 mg/kg
      i.p., -30 min) blocked this response, whilst the alpha 1-adrenoceptor blocker
      prazosin (1 mg/kg i.p.) and the 5-HT1A receptor antagonist, SDZ 216-525 (methyl 4
      (-[4-(1,1m3-trioxo-2H-1,2-benzoisothiazol-2-yl)butyl ]-1-piperazinyl)1H- indole-2
      carboxylate; 1 mg/kg i.p.) were inactive. Another alpha 1-adrenoceptor agonist,
      St 587 (2-(2-chloro-5-trifluoromethylphenylimino)-imidazoline; 1 mg/kg i.p.) did
      not alter body temperature. SDZ NVI-085-induced hypothermia in guinea-pigs is
      probably mediated by 5-HT1D receptors.

PMID- 8575521
TI  - Intermittent cocaine exposure causes delayed and long-lasting sensitization of
      cocaine-induced ACTH secretion in rats.
AB  - In view of the possible role of the hypothalamus-pituitary-adrenal axis in the
      long-term effects of drugs of abuse, we studied the response of the hypothalamus
      pituitary-adrenal axis to cocaine challenges 3 and 14 days after cocaine
      withdrawal. Three days after intermittent cocaine exposure, the cocaine-induced
      increase of plasma adrenocorticotropic hormone (ACTH) is unchanged, whereas after
      14 days the ACTH response is enhanced 2-fold. The cocaine-induced increase of
      plasma corticosterone is enhanced approximately 1.5-fold both 3 and 14 days after
      cocaine withdrawal. Apparently, prior cocaine treatment causes a delayed
      sensitization of cocaine-induced ACTH secretion and long-lasting corticosterone
      hyper-responsiveness. We propose that the long-lasting changes in the
      hypothalamus-pituitary-adrenal axis may facilitate drug-induced long-term
      behavioral sensitization.

PMID- 8575524
TI  - Modulation of AMPA/kainate receptors by cyclothiazide increases cytoplasmic free
      Ca2+ and 45Ca2+ uptake in brain neurons.
AB  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-induced Ca2+
      responses, and their modulation by cyclothiazide, were investigated in two
      functional assays of Ca2+ channel activity. AMPA produced a marked increase in
      cytoplasmic free Ca2+ levels ([Ca2+]i) in single cortical neurons, whereas no
      such effects of AMPA could be observed in intact cerebellar granule neurons. In
      monolayer cultures of cortical cells, cyclothiazide caused a pronounced
      enhancement of AMPA-induced stimulation of 45Ca2+ uptake, whereas similar studies
      in cerebellar granule neurons revealed only a weak potentiation of AMPA-induced
      45Ca2+ uptake. Higher concentrations of cyclothiazide alone produced [Ca2+]i
      oscillations as well as an increase of basal 45Ca2+ uptake in cortical neurons,
      whereas no such effects were obtained in cerebellar granule neurons. Our data
      indicate that AMPA receptors located on cortical and cerebellar granule neurons,
      respectively, may differ in their permeability to Ca2+ and that this difference
      is markedly potentiated following the application of cyclothiazide.

PMID- 8575522
TI  - Identification of 2-amino-2-methyl-4-phosphonobutanoic acid as an antagonist at
      the mGlu4a receptor.
AB  - 2-Amino-2-methyl-4-phosphonobutanoic acid (MAP4) was tested for interactions with
      the mGlu4a receptor which when expressed in baby hamster kidney (BHK570) cells
      couples to inhibition of forskolin-stimulated cAMP production. MAP4 had no
      agonist activity at this receptor and caused a concentration-dependent inhibition
      of the reduction in forskolin-stimulated cyclic AMP formation elicited by L-2
      amino-4-phosphonobutanoic acid (L-AP4). Inhibition by MAP4 was consistent with a
      competitive mechanism of action (Schild slope = 1.2) with a Ki of 190 microM.
      MAP4 is the first antagonist identified for the mGlu4a receptor.

PMID- 8575523
TI  - Feedforward control of agonist-induced Ca2+ signalling by protein kinase C in
      airway smooth muscle cells.
AB  - In isolated bovine tracheal smooth muscle cells, the potent and specific protein
      kinase C inhibitor GF 109203X caused an inhibition of methacholine-and histamine
      induced Ca2+ mobilization and influx, indicating for the first time that protein
      kinase C activation induced by contractile agonists exerts a positive feedforward
      control of Ca2+ signalling by these agonists.

PMID- 8575525
TI  - Modulation of Ca(2+)-activated K+ channel activity by tyrosine kinase inhibitors
      in vascular smooth muscle cell.
AB  - The effects of the tyrosine kinase inhibitors genistein, lavendustin A, and
      tyrphostin A25 on Ca(2+)-activated K+ channel activities in freshly isolated
      single vascular smooth muscle cells from the rat tail artery were studied by
      patch clamp recording technique. Genistein (5-50 microM) and lavendustin A (10
      microM) increased whole-cell Ca(2+)-activated K+ channel currents. Increase in
      single channel activities by genistein and lavendustin A was also observed in
      excised inside-out patches. Diadzein (15 microM), an inactive analogue of
      genistein, did not alter channel activities. Tyrphostin A25 (10 nM), which had no
      significant effect on whole-cell currents in concentrations up to 50 microM,
      increased the open probability of the channels by 841% in inside-out patches. No
      potentiation of whole-cell and single channel activities by genistein was
      observed when ATP was omitted from the intracellular solutions. These
      observations suggest that tyrosine kinase modulates Ca(2+)-activated K+ channel
      activities in vascular smooth muscle cells.

PMID- 8575526
TI  - Stereoselective inhibition of muscarinic receptor subtypes by the eight
      stereoisomers related to rociverine.
AB  - The chemical structure corresponding to 1-hydroxy[1,1'-bicyclohexyl]-2-carboxylic
      acid 2-(diethylamino)-1-methylethyl ester has the classical profile of ester-type
      antimuscarinic drugs. The presence of three chiral carbons leads to eight
      stereoisomers and the substitutions on the cyclohexyl ring generate cis-isomers
      (1, named rociverine) and trans-isomers (2). The aim of this study was to
      determine the binding pattern of the eight stereoisomers and two derived
      compounds, (1S,2S)-1-hydroxy[1,1'-bicyclohexyl]-2-carboxylic acid 2
      (dimethylamino)-1-ethyl ester (3) (1S,2S)-1-hydroxy[1,1'-bicyclohexyl]-2
      carboxylic acid (S)-2-(diethylamino)-1-methylethyl ester methyl iodide (4), at
      the five cloned muscarinic receptors stably expressed in chinese hamster ovary
      cells, in order to define how stereochemical modifications could affect the
      affinity. Our data showed that cis-stereoisomers exhibited higher variations in
      affinity than trans-stereoisomers. Among the cis-stereoisomers, those with the
      (1R,2R) configuration showed considerably higher affinities (up to 240-fold) than
      those with the (1S,2S) configuration. The (1S,2S) configuration was important for
      binding selectivity; this was confirmed also by the use of the two additional
      compounds.

PMID- 8575528
TI  - Specific accumulation of inositol 1,4,5-trisphosphate in rabbit basilar artery in
      response to noradrenaline but not 5-hydroxytryptamine.
AB  - This study examined the ability of 5-hydroxytryptamine and noradrenaline to
      stimulate inositol 1,4,5-trisphosphate (IP3) mass accumulation in segments of the
      rabbit basilar artery. 5-Hydroxytryptamine (5-HT, 100 microM) failed to stimulate
      any significant accumulation of IP3 during the 5 min period following its
      application. In the presence of prazosin, 5-HT (300 microM) caused a rapid,
      transient decrease in IP3 accumulation which was significant after 5 s but had
      increased to pre-stimulation levels within 15 s. In contrast, noradrenaline (10
      microM) stimulated a rapid, transient accumulation of IP3 which was significant
      after 5 s but had declined to basal levels after 60 s. In basilar artery segments
      bathed in Krebs solution containing 25.7 mM K+ (normal concentration 5.7 mM), the
      basal IP3 concentration was significantly elevated. The IP3 accumulation
      stimulated by either 5-HT or raised K+ was not reduced by the presence of the
      alpha 1-adrenoceptor antagonist, prazosin (0.1 microM). In the presence of raised
      K+, 5-hydroxytryptamine caused a rapid, transient inhibition of the K(+)-induced
      IP3 accumulation, which was maximal after 5 s but had increased to pre
      stimulation levels within 30 s in the continued presence of 5-hydroxytryptamine.
      Noradrenaline did not affect the IP3 accumulation induced by raised extracellular
      [K+]. These results provide further evidence that IP3 is not involved in 5
      hydroxytryptamine-induced smooth muscle contraction in the rabbit basilar artery,
      but support a role for this second messenger in the contraction induced in
      response to noradrenaline.

PMID- 8575527
TI  - Protection by lazaroids of the erythrocyte (Ca2+, Mg2+)-ATPase against iron
      induced inhibition.
AB  - The calmodulin-stimulated (Ca2+, Mg2+)-ATPase (calmodulin-ATPase) of the
      erythrocyte membrane is susceptible to oxidative stress induced by heme and non
      heme iron. There is a time-and concentration-dependent inhibition of the
      calmodulin-ATPase activity when the erythrocyte membranes are treated with either
      iron or hemin. In the present study, the calmodulin-ATPase has been used as a
      model system to evaluate the protective effects of a vitamin E analog (U83836E)
      and two 21-aminosteroids (U74500A and U74389G) against calmodulin-ATPase
      inhibition induced by iron and hemin. The drugs, lazaroids from Upjohn, can
      significantly protect the enzyme against iron-induced inhibition and also causes
      a decrease in the formation of thiobarbituric acid reactive species, with an IC50
      of 0.4 microM for the drug U83836E and 4 microM for the drug U74500A. The 21
      aminosteroid U74389G does not restore iron-inhibited calmodulin-ATPase activity
      under similar conditions. At higher concentrations (> 100 microM) all three drugs
      inhibit the calmodulin-ATPase activity. None of the drugs tested can restore
      hemin-inhibited calmodulin-ATPase activity.

PMID- 8575529
TI  - Characterisation of inositol 1,4,5-trisphosphate binding sites in rabbit aortic
      smooth muscle.
AB  - The present study investigated the characteristics of D-myo-inositol 1,4,5
      trisphosphate (Ins(1,4,5)P3) binding sites in crude membrane preparations of
      rabbit aortic smooth muscle. A particular aim was to demonstrate if increases in
      cytoplasmic cyclic guanosine 3':5' monophosphate (cGMP), which mediates the
      effect of nitrovasodilators, may cause smooth muscle relaxation in part by the
      displacement of Ins(1,4,5)P3 binding. Negligible Ins(1,4,5)P3 binding was
      observed at pH < 7, while maximum binding occurred over the pH range 8-9.
      Saturation analysis of isotopic dilution binding data revealed an apparently
      homogenous population of Ins(1,4,5)P3 binding sites with a KD of 4.02 +/- 0.53 nM
      and a Bmax of 27.7 +/- 4.6 fmol/mg protein. Heparin, an Ins(1,4,5)P3 receptor
      antagonist, inhibited binding with an IC50 of 11.43 +/- 2.81 micrograms/ml. The
      ability of other polyphosphate compounds to inhibit Ins(1,4,5)P3 binding in this
      preparation was also examined. D-myo-Inositol 1,3,4,5-tetrakisphosphate
      (Ins(1,3,4,5)P4), adenosine 5'-triphosphate (ATP) and guanosine 5'-triphosphate
      (GTP) inhibited Ins(1,4,5)P3 binding, although each was significantly less potent
      that Ins(1,4,5)P3. In contrast, cyclic guanosine 3':5' monophosphate (cGMP) did
      not significantly alter Ins(1,4,5)P3 binding in rabbit aortic smooth muscle. This
      observation suggests that competitive inhibition of Ins(1,4,5)P3 receptor binding
      is not an important consideration in cGMP-mediated vascular smooth muscle cell
      relaxation.

PMID- 8575530
TI  - Molecular pharmacology of LR-B/081, a new non-peptide angiotensin AT1 receptor
      antagonist.
AB  - This report describes the molecular pharmacological properties of LR-B/081
      (methyl 2-[[4-butyl-2-methyl-6-oxo-5-[[2'-(1H-tetrazol-5- yl) [1,1'-biphenyl]-4
      yl]methyl]-1 (6H)-pyrimidinyl]methyl]- 3-thiophenecarboxilate), a novel non
      peptide angiotensin II receptor antagonist. This compound potently displaced
      [3H]angiotensin II from angiotensin AT1 (Ki = 1.4 nM, rat adrenal cortex), but
      not from angiotensin AT2 (Ki > 1 microM, bovine cerebellar cortex) receptors and
      did not show affinity for other receptor systems (Ki > 10 microM). In saturation
      studies, LR-B/081 both increased KD and decreased Bmax values in a dose-dependent
      fashion. The rate of dissociation of [3H]angiotenin II from angiotensin AT1
      receptors was not affected by the presence of 1 microM LR-B/081 and the
      association rate of [3H]angiotensin II was not decreased by the presence of 1 or
      30 nM LR-B/081, indicating that the Bmax reduction was not due to an allosteric
      interaction or to a delay in reaching the steady-state conditions. These data
      underline the complexity of the antagonistic nature of LR-B/081, presenting
      features of both competitive and noncompetitive antagonism.

PMID- 8575531
TI  - The 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide interacts with the
      dopamine transporter in rat brain synaptosomes.
AB  - The ability of the 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide to bind to
      the dopamine transporter and inhibit [3H]dopamine uptake was investigated in rat
      brain synaptosomes from the nucleus accumbens and caudate putamen. Competitive
      displacement experiments showed that 1-(m-chlorophenyl)-biguanide inhibited the
      binding of [3H]GBR-12935 in a biphasic manner (IC50 values of 0.4 and 2.0 microM
      [high affinity] and 34.8 and 52.7 microM [low affinity] for caudate putamen and
      nucleus accumbens, respectively), and the high affinity binding site differed
      between brain regions. Serotonin was ineffective at competing for [3H]GBR-12935
      binding, while the selective 5-HT3 receptor antagonist ICS 205-930 exhibited an
      IC50 > 100 microM. The maximum density of [3H]GBR-12935 binding sites was more
      than two-fold greater in the caudate putamen than in the nucleus accumbens (6.9
      vs. 2.7 pmol/mg protein), and KD values were similar (4.7 and 4.2 nM). 1-(m
      chlorophenyl)-biguanide was able to inhibit [3H]dopamine uptake into synaptosomes
      of both brain regions, however it was significantly more potent in the caudate
      putamen (IC50: 5.1 vs. 6.5 microM). The results demonstrate that some of the
      reported dopamine releasing effects of 1-(m-chlorophenyl)-biguanide may be due in
      part to activity at the dopamine transporter, and further suggest a possible
      difference in dopamine uptake parameters between the caudate putamen and nucleus
      accumbens.

PMID- 8575532
TI  - Rolipram increases cyclic GMP content in L-arginine-treated cultured bovine
      aortic endothelial cells.
AB  - Cultured bovine aortic endothelial cells only contain two cyclic nucleotide
      phosphodiesterases isoforms: PDE II (cyclic GMP stimulated) and PDE IV (rolipram
      sensitive). The effects of cilostamide or rolipram alone or together, on cyclic
      AMP and cyclic GMP levels, were measured in indomethacin-treated endothelial
      cells alone or in the presence of nitric oxide (NO) modulators. In all
      conditions, cyclic AMP levels were potently increased (8-13-fold) only when PDE
      II and PDE IV inhibitors were given together. Cyclic GMP levels were not modified
      by these PDE inhibitors in control and NG-nitro-L-arginine-methyl ester-treated
      cells. But surprisingly, in L-arginine-treated cells, cyclic GMP content was
      increased by 42% by rolipram alone, and combination of rolipram with cilostamide
      resulted in a further increase in cyclic GMP content (to 153% compared to control
      cells). These results suggest that in presence of the NO synthase substrate (L
      arginine), an increase in cyclic AMP level may upregulate the L
      arginine/NO/cyclic GMP pathway.

PMID- 8575533
TI  - Rolipram inhibition of phosphodiesterase-4 activation.
AB  - Rolipram inhibited U937 cell phosphodiesterase-4 in either the presence or
      absence of saturating (100 micrograms/ml) phosphatidic acid in an apparently
      phospholipid-independent manner, exhibiting similar kinetics (Ki values = 0.41
      and 0.59 microM, respectively). At low concentrations (10 and 100 nM), however,
      rolipram caused a rightward shift of the phosphatidic acid concentration-response
      curve for phosphodiesterase-4 activation, suppressing activation by up to 70%.
      Maximum inhibition of phosphodiesterase-4 activation occurred at phosphatidic
      acid concentrations of 5-40 micrograms/ml. The results suggest that rolipram is
      capable of inhibiting phosphodiesterase-4 by both phospholipid-dependent and
      phospholipid-independent mechanisms.

PMID- 8575534
TI  - Cholecystokinin and gastrin are not equally sensitive to GTP gamma S at CCKB
      receptors: importance of the sulphated tyrosine.
AB  - We have shown that gastrin and cholecystokinin octapeptide (CCK-8) are
      differently coupled to G protein (GTP-binding protein) through type B
      cholecystokinin receptors in guinea-pig brain membranes and Jurkat cells. Indeed,
      the gastrin-13 binding affinity is strongly reduced by stable guanyl nucleotides,
      whereas CCK-8 binding is only slightly affected. In order to determine the
      structural requirements regulating such coupling, we have synthesized several
      gastrin and cholecystokinin fragments (sulphated or unsulphated) elongated at the
      N-terminus of the common C-terminal tetrapeptide. We investigated their
      interaction with CCKB receptors in guinea pig brain membranes and Jurkat cells
      and their involvement in the G protein coupling. Their apparent binding
      affinities to CCKB receptors were measured by inhibition of [125I]Bolton Hunter
      CCK-8 (3-[125I]iodo-4-hydroxyphenyl)propionyl-CCK-8) binding in the presence or
      absence of GTP gamma S (guanosine 5'-O-(3-thio)triphosphate) or aluminum
      tetrafluoride (AlF4-). Activation of the G proteins by GTP gamma S or AlF4- led
      to a decrease in binding affinity for the gastrin related peptides, the common
      CCK-gastrin C-terminal forms, the cholecystokinin hexapeptide and the unsulphated
      cholecystokinin heptapeptide. Sulphated CCK-7, CCK-8, and cionin apparent binding
      affinities were not affected. These finding indicated that the sulphated tyrosine
      in position 7 in CCK (as counted from the C-terminus), provides the
      cholecystokinin selectivity for the CCKB receptor compared to gastrin. The
      results are discussed with the aim to better clarify the physiological relevance
      of gastrin and cholecystokinin toward CCKB receptors and their related
      intracellular events.

PMID- 8575535
TI  - Aldosterone inhibits nitric oxide synthesis in rat vascular smooth muscle cells
      induced by interleukin-1 beta.
AB  - We investigated the effects of aldosterone on nitric oxide (NO) synthesis in
      vascular smooth muscle cells. We measured the production of nitrite, a stable
      metabolite of NO, and the expression of inducible NO synthase mRNA and protein in
      cultured rat vascular smooth muscle cells. Incubation of the cultures with
      interleukin-1 beta (10 ng/ml) for 24 h caused a significant increase in nitrite
      generation. The interleukin-1 beta-induced nitrite production by vascular smooth
      muscle cells was significantly inhibited by aldosterone in a dose (10(-9)
      approximately 10(-6) M)-dependent manner. Incubation with interleukin-1 beta for
      12 approximately 24 h caused inducible NO synthase mRNA expression in vascular
      smooth muscle cells, whereas aldosterone had a suppressive effect on its
      expression. Aldosterone also decreased interleukin-1 beta-induced NO synthase
      protein accumulation. These results indicate that aldosterone inhibits NO
      synthesis under interleukin-1 beta-stimulated conditions in vascular smooth
      muscle cells.

PMID- 8575536
TI  - Two human alpha 2-adrenoceptor subtypes alpha 2A-C10 and alpha 2B-C2 expressed in
      Sf9 cells couple to transduction pathway resulting in opposite effects on cAMP
      production.
AB  - The baculovirus expression vector system utilizing the strong polyhedrin gene
      promoter of the Autographa californica nuclear polyhedrosis virus (AcNPV) was
      used for high level expression of the two alpha 2-adrenoceptor subtypes alpha 2A
      C10 and alpha 2B-C2 in Spodoptera frugiperda (Sf-9) insect cells. For rapid
      screening of recombinant viruses the luciferase gene was expressed under the
      early ETL-promoter (early transcript large) in the same plasmid. Both receptor
      subtypes showed the same rank order of binding affinity for four agonists tested:
      dexmedetomidine > l-medetomidine = clonidine > noradrenaline. For the alpha 2A
      C10 subtype, these agonists inhibited forskolin stimulated cAMP production
      through pertussis toxin sensitive G-proteins. In contrast, for the alpha 2B-C2
      subtype the agonists stimulated both basal and forskolin stimulated cAMP
      production.

PMID- 8575538
TI  - Functional effects of the 5-HT1D receptor antagonist GR 127,935 at human 5-HT1D
      alpha, 5-HT1D beta, 5-HT1A and opossum 5-HT1B receptors.
AB  - The functional activity and selectivity of the novel 5-HT1D receptor antagonist
      GR 127,935 (2'-methyl-4'(5-methyl-1,2,4 oxadiazol-3-yl)-biphenyl-4-carboxylic
      acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide) was investigated at
      cloned human 5-HT1A, 5-HT1D alpha, 5-HT1D beta and opossum kidney (OK) 5-HT1B
      receptor sites. 5-HT1 receptor-mediated activity was studied by measuring the
      inhibition of forskolin-induced cAMP formation in cell lines expressing these
      receptors (Bmax (fmol/mg protein): human epitheloid carcinoma HeLa/5-HT1A: 1285,
      OK/5-HT1B: 52, Chinese hamster ovary CHO-K1/5-HT1D alpha: 181 and CHO-K1/5-HT1D
      beta: 685). GR 127,935 did not show 5-HT1D beta receptor-mediated agonist
      activity in permanently transfected CHO-K1 cells, whereas at submicromolar and
      higher concentrations intrinsic agonist activity was observed in HeLa/5-HT1A,OK/5
      HT1B and CHO-K1/5-HT1D alpha cells. GR 127,935 showed potent (KB value: 1.3 nM)
      and silent antagonism at CHO-K1/5-HT1D beta receptor sites. The antagonist
      activity of 1 microM of GR 127,935 at CHO-K1/5-HT1D alpha and OK/5-HT1B receptor
      sites was only partial and less pronounced. This contrasts with the silent
      antagonism of methiothepin at the 5-HT1D alpha (KB value = 11.8 nM), 5-HT1D beta
      (KB value = 6.9 nM) and 5-HT1B (KB value = 49.3 nM) receptor subtypes. GR
      127,935, when tested at 10 microM, was found to be a weak and partial antagonist
      of HeLa/5-HT1A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8575537
TI  - Binding of distamycin and chromomycin to human immunodeficiency type 1 virus DNA:
      a non-radioactive automated footprinting study.
AB  - Sequence-selectivity of DNA-binding drugs was recently reported in a number of
      studies employing footprinting and gel retardation approaches. In this paper we
      studied sequence-selectivity of the binding of chromomycin and distamycin to DNA
      by performing DNase I footprinting and analysis of the cleaved fragments by the
      Pharmacia ALF DNA Sequencing System. As a model system we employed the long
      terminal repeat of the human immunodeficiency type 1 virus. The main conclusion
      of our experiments is that automated analysis of DNase I footprinting is a fast
      and reliable technique to study drugs-DNA interactions. The results obtained
      suggest that distamycin and chromomycin differentially interact with the long
      terminal repeat of the human immunodeficiency type 1 virus; this differential
      binding depends upon the DNA sequences recognized. The data presented are
      consistent with a preferential binding of distamycin to DNA sequences of the
      binding sites of nuclear factor kappa B and transcription factor IID. By
      contrast, distamycin exhibits only weak binding to DNA sequences recognized by
      the promoter-specific transcription factor Sp1. Unlike distamycin, chromomycin
      preferentially interacts with the binding sites of the promoter-specific
      transcription factor Sp1.

PMID- 8575539
TI  - Fine structure of the parotid gland in tree shrew (Tupaia glis).
AB  - The parotid glands of Tupaia glis were examined by light and transmission
      electron microscopy. The acinar cells were seromucous in nature, and contained
      many acidophilic granules with strong affinity for periodic acid-Schiff (PAS) and
      weak affinity for alcian blue (AB). These granules consisted of a fine granular
      matrix of moderate density in which a denser corpuscles or semilunar materials
      were present. Intercalated duct cells had a few fine vesicles, vacuoles and very
      few dense granules in the apical region. In occasional epithelial cells,
      acidophilic, PAS-positive and AB-negative bodies with moderate density were
      observed in the supranuclear region. The striated ducts consisted of columnar
      light and dark cells containing round or small ovoid granules of moderate density
      and did not show the granular duct as seen in the parotid glands of kobe mole and
      tenrec which are placed in the order insectivora.

PMID- 8575540
TI  - Gene transfer into circulating primordial germ cells of quail embryos.
AB  - During early stages in avian embryogenesis primordial germ cells (PGCs) show a
      unique migration pathway toward the gonadal anlage through the circulation. In
      the present study, liposomes consisting of plasmid DNA (pMiwZ; containing lacZ as
      a reporter) and Lipofectin were injected into the marginal veins of quail embryos
      during the stages PGCs were circulating in the blood vessels. The lacZ expression
      was then histochemically detected in the gonads at later embryonic stages,
      indicating the expression of the injected DNA in PGCs.

PMID- 8575541
TI  - Dermal histology of hairless rat derived from Wistar strain.
AB  - The dermal histology of 9-week-old hairless rats derived from Wistar rats was
      investigated and compared with that of age-matched Wistar rats. Skin samples were
      taken from 4 portions: the head, dorsal and ventral skin, and foot pad. The
      epidermis of the 3 portions other than the foot pad was thicker in hairless rats
      than in Wistar rats. The hair canals of hairless rats contained lamellar
      cornified tissues instead of hair, and some of the hair follicles deep in the
      dermis exhibited cyst formation. S-100-immunoreactive cells were detected in the
      basal layer of epidermis and their number in hairless rats was greater than that
      in Wistar rats. Ultrastructurally, electron-lucent cells, i.e. Langerhans cells,
      which contained Birbeck granules and/or cored tubules, were observed more
      frequently in the epidermis of hairless rats than in that of Wistar rats. Some
      cells in one hairless rat, which had similar characteristics to Langerhans cells
      without Birbeck granules, contained confronting cisternae.

PMID- 8575542
TI  - Comparison of adrenocortical zonation in C57BL/6J and DDD mice.
AB  - Adrenal weights and adrenocortical zonation were compared in two inbred mouse
      strains, C57BL/6J and DDD, which are different in both origin and genetic
      background. Clear strain and sex differences were observed in the adrenal weight
      and the morphology of the zona fasciculata, z. reticularis and X zone. DDD
      adrenals were larger than C57BL/6J ones regardless of sex. The z. fasciculata was
      thicker in female than male DDD mice. The z. reticularis of DDD males developed
      nodules at 70 days of age, followed by an increase in size with age, while that
      of C57BL/6J males did not. Parous females experiencing pregnancy, gestation and
      lactation also developed similar nodules, but virgins did not. The X zone
      degeneration occurred earlier in males than in females. This zone disappeared
      before 5 weeks of age in males but gradually decreased in thickness with age in
      DDD virgins. The female X zone was thicker and degenerated with vacuolation in
      DDD, while it was thinner and degenerated without vacuolation in C57BL/6J. Such
      clear strain differences in the inner cortices, z. reticularis and X zone,
      suggested that their morphology might be regulated primarily by genetics and
      modified by endocrinology.

PMID- 8575543
TI  - Dorsal skin reactions to sunlight and artificial ultraviolet light in hairless
      descendants of Mexican hairless dogs.
AB  - Dorsal skin reactions to irradiation with two different types of ultraviolet (UV)
      light sources (sunlight and artificial UV light) were investigated in hairless
      descendants of Mexican hairless dogs. The total energy dose of solar UV exposure
      and artificial UV irradiation was 90 kJ/m2 and 40 kJ/m2, respectively.
      Histological examinations were done up to 7 days after UV irradiation (7 DAI). At
      1 DAI, the solar UV-exposed skin did not show marked changes, while artificial UV
      irradiated skin exhibited a visible erythematous reaction and prominent
      histological alterations such as epidermal thickening, appearance of sunburn
      cells and deformation elastic fibers. At 4 DAI of solar UV-exposure, the skin
      color became moderately dark and noticeable pigmentation developed in the
      epidermis. In contrast, at 4 DAI of artificial UV irradiation, there still
      remained moderate degeneration in the epidermis and dermis, and delayed tanning
      was weak. At 7 DAI of solar exposure, delayed suntan reactions became more
      prominent. Histologically, there were heavy pigmentation of melanin granules
      mainly in the stratum basale. On the other hand, artificial UV irradiated skin
      showed less pigmentation. Thus, solar exposure provoked remarkable pigmentation
      while artificial UV irradiation brought about severe sunburn reactions in the
      dorsal skin of hairless dogs.

PMID- 8575544
TI  - Chromosomal localization of a strain-specific p53-related sequence in rat (Rattus
      norvegicus).
AB  - Strain-specific restriction fragments hybridizing to human p53 gene cDNA, which
      was detected in only particular strains of inbred rat were revealed by Southern
      blot hybridization of DNAs of various inbred rat strains. Chromosomal location of
      the strain-specific fragments was determined on rat chromosome 1 between Kal and
      Pkc loci by linkage analysis using microsatellite marker loci. The fragments were
      concluded to be a novel p53-related sequence which is present in particular rat
      strains and absent from the remaining strains.

PMID- 8575545
TI  - Effects of age at first-pairing on the reproductive performance of Mongolian
      gerbils (Meriones unguiculatus).
AB  - Effects of age at first-pairing on the reproductive performance of the gerbil
      were studied throughout the reproductive life. Six groups of 7-30 female gerbils
      were paired monogamously with males at different ages. Out of 101 pairs in 6
      groups, 79 (78.2%) produced 1 or more litters. The mean litter size at birth and
      mean weaning rate of 846 litters were 4.4 (totally 3,733 pups) and 67.4% (2,517
      pups), respectively. Reproduction was compared in the 6 age groups. The littering
      rate (No. of females with litters/No. of female paired) was significantly lower
      in two groups in which mature females were paired with age-matched males (Group
      4) or the oldest females with younger, sexually mature males (Group 6). The
      interval from pairing to the first litter was shortest in two groups in which
      mature females were paired with one month older, sexually mature males (Groups 3
      and 5). Although the oldest pairs (Group 6) produced about 7 litters, the pairs
      from the other 5 groups produced about 10 or more litters throughout their
      reproductive life. The weaning rate was significantly higher in Group 6 (the
      oldest pairs) than in the younger groups. The effects of parity on reproduction
      were estimated from the data for the 61 pairs which produced more than 8 litters
      in the 6 groups. The number of pups at birth and the weaning rate were decreased
      in last 20-30% of the total parity in all 6 groups, although the age at the last
      litter in all groups was significantly different. The data suggest that any
      decline in reproduction may be due to not age but parity in the Mongolian gerbil.

PMID- 8575546
TI  - Testicular spermatid and epididymal sperm head counts as an indicator for
      reproductive toxicity in rats.
AB  - The testes of rats were exposed to a single soft x-ray irradiation at levels of
      10, 25 and 63 Gy. Testicular and cauda epididymal weights and their sperm counts
      were decreased at 7 weeks after the irradiation. Histologically, there was an
      evidence of interrupted spermatogenesis dose-dependently. Animal mating trails,
      in which irradiated males were mated with untreated females revealed a slight
      increase in early stage of postimplantation loss at as low as 10 Gy. There were
      increases in preimplantation and early stage of postimplantation losses in the
      group of irradiated at 25 Gy. Infertility occurred in irradiated males at 63 Gy.
      The effects of irradiation were more severe on the sperm count parameters than on
      reproductive organ weights, histological examination and reproductive status. The
      testicular spermatid and epididymal sperm head counts are considered to be useful
      indicators to detect quantitatively the adverse effects on spermatogenesis.

PMID- 8575547
TI  - Deoxyribonuclease II (DNase II) activity is regulated systemically by a single
      locus in mice.
AB  - A survey of inbred strains of mice revealed genetic variation in DNase II
      activity in the spleen, liver, kidney, lung, heart, coagulating gland and
      preputial gland. Since DNase II activities in these tissues were closely
      correlated to each other, systemic regulation of the enzyme was suggested. The
      inheritance of quantitative variation in the DNase II activity was studied in a
      test cross using the spleen DNase II activity level as an indicator of progeny
      phenotypes. The results showed that the strain difference in DNase II activity
      was controlled by a single autosomal locus. The locus for the mouse DNase II
      activity level, designated as Dnl2al, had at least two alleles. The allele
      Dnl2ala determines high DNase II activity and occurs in C57BL/6 and C3H/He
      strains. The other allele Dnl2alb determines low enzyme activity and occurs in
      BALB/c and DBA/2 strains.

PMID- 8575548
TI  - Globule leukocytes in transitional cell hyperplasia and carcinomas of aged mice.
AB  - Globule leukocytes (GLs) infiltrating in transitional cell hyperplasia and
      carcinomas of aged BDF1 mice were pathologically examined. The intracytoplasmic
      granules of globule leukocytes showed a variety of reactivity to histochemical
      staining for polysaccharides and were ultrastructurally composed of homogeneous
      electron dense material, occasionally containing crystaloids or vesicles. The GL
      infiltrating in tumor tissue is extremely rare.

PMID- 8575549
TI  - Detection of cilia-associated respiratory bacillus in experimentally and
      naturally infected mice and rats by the polymerase chain reaction.
AB  - Cilia-associated respiratory (CAR) bacillus was detected by means of the reverse
      transcription (RT)-polymerase chain reaction (PCR), and the results were compared
      with those of indirect immunofluorescence test (IFAT) for the detection of the
      organism. In the experimental infections, 15 mice were in contact with mice
      previously inoculated with CAR bacillus. Three mice each were tested at days 3,
      5, 7, 12 and 20 postexposure. On day 3 postexposure, CAR bacillus was detected in
      oral swab samples from all 3 mice by RT-PCR, but was not detected in any sampling
      sites from the mice by IFAT. Total numbers of positive samples from nasal, oral
      and tracheal swabs obtained through the test were 6/15, 14/15 and 8/15,
      respectively, by RT-PCR, and 2/15, 6/15 and 3/15, respectively by IFAT. For the
      detection of CAR bacillus in samples from 52 rats, 34 serum antibody negative
      rats by enzyme-linked immunosorbent assay were also negative by RT-PCR and IFAT
      except for one sample from the oral cavity, and all serum antibody positive rats
      were positive for the organism by RT-PCR but it could not be detected in five of
      them by IFAT. By means of RT-PCR, no differences in the positive rates depending
      on sampling sites were observed except in one rat. The RT-PCR was found to be a
      specific, highly sensitive and reliable procedure for detecting CAR bacillus in
      mice and rats. The oral cavity was the most suitable site for the diagnosis of
      the early stage of this infection by RT-PCR.

PMID- 8575551
TI  - Case report on situs inversus totalis in two Sprague-Dawley rats.
AB  - We macro- and microscopically examined two cases of congenital visceral
      transposition (situs inversus totalis) in SD rats. We also investigated the
      possibility of situs inversus in association with immotile-cilia syndrome. The
      rats had grown normally with no clinical signs of disease. Although all organs
      including the vascular system were located opposite to the normal position and
      displayed a mirror image on macroscopic observation, no abnormality was found in
      any of the organs on microscopic examination. Electron-microscopic observation
      revealed in neither animal any structural abnormalities of the cilia and
      flagella, which are one of the diagnostic characterizations of immotile-cilia
      syndrome. Congenital transposition of the viscera is rare and there are few
      reports examining complications with situs inversus in rats. This report will be
      helpful in accumulating information on this condition.

PMID- 8575550
TI  - Peritoneal mast cell hyperplasia in rats after IgE antibody-antigen interaction.
AB  - Peritoneal mast cell hyperplasia was investigated in rats after evoking IgE
      antibody-antigen reaction. Rats were immunized with antigen and then passively
      sensitized with monoclonal IgE antibody before antigen challenge. A significant
      increase in the number of peritoneal mast cells was observed 3 weeks after the
      antigen challenge in the peritoneal cavity, although the histamine content of the
      mast cells was decreased significantly. In rats without prior immunization, these
      changes were not observed. Stimulation with compound 48/80 or calcium ionophore
      A23187 did not affect the number of mast cells. This model may prove to be a
      useful tool for studying the mechanisms of mast cell hyperplasia and recruitment
      of mast cell precursors in vivo.

PMID- 8575552
TI  - A new spontaneous allele at the pink-eyed dilution (p) locus discovered in Mus
      musculus castaneus.
AB  - Mutant mice characterized by a cream coat and pink eyes were spontaneously
      discovered among the descendants of Indonesian wild mice (Mus musculus
      castaneus). This mutant phenotype was controlled by a single autosomal recessive
      gene that was allelic to the pink-eyed dilution (p) gene. The mutant mouse
      phenotypically resembled the original p mouse which was the first mutant
      identified at this locus. Nevertheless, these two alleles differed in origin, a
      previous report suggesting that the original p allele was derived from Japanese
      wild mice (M. m. molossinus). Thus the symbol pcas (pink-eyed castaneus) was
      proposed for the present mutation allele.

PMID- 8575554
TI  - Ethical principles and guidelines for experiments on animals. Swiss Academy of
      Medical Sciences. Swiss Academy of Sciences.

PMID- 8575553
TI  - Ultrastructure of the dorsal skins of hairless descendants derived from Mexican
      hairless dogs.
AB  - Ultrastructural characteristics of the dorsal skin of hairless descendants
      derived from Mexican hairless dogs (3-month-, 1-year- and 5-year-old) were
      investigated and compared with those of age-matched beagles. Except that beagles
      had no melanocytes in epidermis, there was no essential difference in
      ultrastructural characteristics of epidermis between hairless dogs and beagles.
      In the Stratum basale of epidermis of hairless dogs, a small number of
      melanocytes and a few Langerhans cell (LC)-like cells were observed among
      keratinocytes. Melanocytes contained many melanosomes and a few premelanosomes.
      LC-like cells were characterized by electron-lucent cytoplasm and lobulated
      nucleus and lacked melanin granules, tonofilaments and desmosomal attachments.
      Unlike LC in humans and rodents, these LC-like cells did not contain Birbeck
      granules. Although age-related ultrastructural changes of dorsal skin were
      generally not clear both in hairless dogs and in beagles, cells containing
      melanin granules were not infrequently observed among dermal collagen bundles in
      5-year-old hairless dogs.

PMID- 8575555
TI  - Induction of neovascularization in vivo by glycerol.
AB  - Glycerol, injected into a site between the femoral vessels of the rat, induced
      neovascularization, both from the preexisting microcirculation and from the side
      of the femoral vein facing the artery-vein interstitium where the glycerol was
      administered. The use of glycerol together with a known angiogenic substance
      (PGE2) did not modify the neocapillary density (NCD) obtained with glycerol
      alone. In contrast, the lower level of NCD achieved with an acylglycerol
      (triacetylglycerol) was increased when the latter was associated with PGE2.
      Values reached were similar to, but never higher than, those for glycerol alone,
      or combined with PGE2. The results suggest that glycerol and some substances
      containing glycerol, amongst which 1-butyrylglycerol has been previously
      considered, may stimulate angiogenesis by a direct or indirect mechanism of
      action.

PMID- 8575556
TI  - Excess bioavailability of zinc may cause obesity in humans.
AB  - The body weight or body weight/height ratio exhibits a positive linear
      correlation to hair zinc (Zn) concentration which is more strongly positive in
      men than in women. The obese of both sexes possess higher Zn concentrations in
      their hair than those with normal body weight/height. The degree of obesity
      increases with the increase in the hair Zn concentration.

PMID- 8575557
TI  - Renal effects of a high unsaturated fat diet in renal artery stenosis in rats.
AB  - The renal effects of an unsaturated fat (UNSAT) diet in mild to moderate two
      kidney, one-clip (2K1C) renovascular hypertension were evaluated. An UNSAT diet
      (37% by energy) prevented the development of hypertension compared to 2K1C rats
      fed a high saturated fat (SAT) (37% by energy) and a normal fat (CONTROL) (11% by
      energy) diet. Urinary sodium and fractional sodium excretion increased in 2K1C
      rats as compared to SHAM operated controls, regardless of the diet received. In
      the early weeks of the experiment (weeks 2-4 post-surgery to induce
      hypertension), an enhanced natriuresis occurred in the 2K1C UNSAT as compared to
      the 2K1C CONTROL and SAT diet groups. This resulted from an increase in the
      glomerular filtration rate (GFR in mls.min-1) as measured using the single
      injection [51Cr] EDTA method (2K1C UNSAT; 1.99 +/- 0.18 versus 2K1C SAT; 1.27 +/-
      0.09, p < 0.02; and versus SHAM CONTROL; 1.45 x 0.01; p < 0.02). The increased
      GFR was not associated with alterations in effective renal plasma flow (ERPF) as
      measured using the single-injection [125I] Na hippurate method. No differences in
      sodium excretion; GFR; ERPF or renal blood flow (microsphere technique) were
      noted between the 2K1C UNSAT and SAT diet groups at weeks 6-8 post-surgery,
      despite a continued antihypertensive effect of the UNSAT diet. Hence, the
      antihypertensive effect of an unsaturated fat diet in 2K1C renovascular
      hypertension in rats is associated with transient glomerular changes leading to
      an enhanced natriuresis.

PMID- 8575559
TI  - Leukocyte trafficking in response to magnetic resonance imaging.
AB  - There were significant increases in total T cells and in T helper cells in blood
      samples collected immediately following magnetic resonance imaging (MRI)
      examinations of brains of male volunteers and patients. Percentages of total
      lymphocytes and suppressor/cytotoxic T cells decreased in these same samples.
      There were no significant changes in any leukocyte subpopulations in males
      undergoing lumbar MRI and females undergoing brain MRI. Thus, it is unlikely that
      stress from the procedure is the explanation for these changes. Our results show
      that MRI has specific effects on a brain system(s) that controls lymphocyte
      subpopulations.

PMID- 8575558
TI  - The history of cyclosporin A (Sandimmune) revisited: another point of view.
AB  - The immunosuppressant cyclosporin A (Sandimmune) has become the first line
      treatment for preventing rejection of transplanted organs and for certain
      autoimmune diseases. The discovery of that drug and its preclinical development
      are described, and it is shown that most earlier accounts of the history of this
      compound are, in important respects, incorrect and misleading.

PMID- 8575560
TI  - Evidence for suppression of immune function by insulin-like growth factor-1 in
      dwarf rats in vivo.
AB  - These studies were undertaken to investigate the effects of increasing or
      decreasing IGF-1 levels on aspects of immune function in rats. Female dwarf rats
      were treated with recombinant human IGF-1 or with a potent sheep anti-IGF-serum.
      Body weight, thymus weight and spleen weight increased with IGF-1 treatment (p <
      0.001), while there was no effect of anti-IGF-1 treatment when compared with the
      appropriate normal sheep serum (NSS) treated controls. IGF-1 treatment
      significantly decreased WBC and RBC counts, but increased the ratio of CD4+:CD8+
      T-cells. Anti-IGF-1 serum had no effect on these parameters compared with NSS.
      However anti-IGF-1 was associated with increased T-cell numbers, decreased
      natural killer cells, and enhancement of the animals' ability to produce specific
      IgG in response to injection of keyhole limpet haemocyanin (KLH). These results
      indicate that IGF-1 may suppress immune function although increasing the size of
      immune organs such as spleen.

PMID- 8575561
TI  - Involvement of H1 receptors in the central antinociceptive effect of histamine:
      pharmacological dissection by electrophysiological analysis.
AB  - Intracerebroventricular (i.c.v.) administration of histamine (HA, 0.025-0.1
      microM/rat) to arthritic rats induces a dose-related inhibition of the neuronal
      thalamic firing evoked by peripheral noxious stimuli. To characterize the type(s)
      of HA receptors involved in this depressing activity of the amine we used
      electrophysiological techniques to examine the effects of i.c.v. administration
      of H1 and H2 agonists and antagonists on the spontaneous and evoked nociceptive
      firing of the thalamic neurons in rats rendered arthritic by Freund's adjuvant.
      The H1 agonist 2-pyridylethylamine (0.4-1.0 microM/rat, i.c.v.) displayed a dose
      dependent antinociceptive effect very similar to that of HA, while the H2 agonist
      dimaprit (0.05-0.2 microM/rat, i.c.v.) did not modify thalamic firing. Neither
      mepyramine (H1 antagonist, 0.1 microM/rat, i.c.v.) nor zolantidine (H2
      antagonist, 0.01 microM/rat, i.c.v.) modified the evoked firing of rat thalamic
      neurons. When administered before HA (0.1 microM/rat, i.c.v.) mepyramine but not
      zolantidine was able to inhibit the antinociceptive effect of HA. On the basis of
      the present electrophysiological results, we suggest that a specific interaction
      of histamine with H1 receptors may be important for its antinociceptive effect on
      afferent peripheral inputs to the thalamus.

PMID- 8575562
TI  - Influence of repeated prazosin administration on cardiovascular responses in rats
      and rabbits.
AB  - Prazosin was injected i.v. at a dose of 50 micrograms/kg every 2 h for 8 h in
      conscious rats. Its hypotensive action significantly declined. A similar effect
      was also observed in rabbits pretreated with prazosin (40 micrograms/kg, i.v.)
      every 1 h for 4 h. In prazosin-treated rabbits, the total peripheral resistance
      became less responsive to phentolamine stimulation. Repeated prazosin
      administration abolished its ability to block receptors in a model of anococcygue
      muscle contraction after noradrenaline (NA) stimulation. The alpha-adrenoceptors
      in anococcygue muscle exhibited lower pD2 to NA and lower pA2 to prazosin in
      prazosin-treated rats. The results demonstrate that repeated prazosin
      administration reduces the effectiveness of alpha-adrenoceptors blockers.

PMID- 8575563
TI  - Tumor necrosis factor-alpha inhibits collagen synthesis in human and rat
      granulation tissue fibroblasts.
AB  - The purpose of the study was to examine the effects of tumor necrosis factor
      alpha (TNF-alpha) on collagen gene expression in rat and human granulation tissue
      fibroblast cultures. The cells were exposed to 0.1, 1, 10, or 100 ng/ml of TNF
      alpha, and the rate of collagen synthesis was measured as synthesis of protein
      bound 3H-hydroxy-proline. Total cellular RNA was isolated from fibroblasts, and
      measurements of specific cellular RNAs from fibroblasts were performed by
      Northern blot hybridizations using 32P-labeled cDNA probes. In cultures of rat
      granulation tissue fibroblasts TNF-alpha decreased 3H-hydroxyproline production
      to about 75% of that in controls and it also decreased pro alpha 1(I) and pro
      alpha 1(III) collagen mRNA levels, maximally to 33% and 23% of the control
      levels, respectively. In cultures of human granulation tissue fibroblasts a
      similar inhibiting effect in the production of collagen was seen. TNF-alpha
      decreased the production of 3H-hydroxyproline to 56% of the control value with a
      dose of 100 ng/ml also having an inhibiting effect on pro alpha 1(I) collagen
      mRNA levels of up to 43% of the control level. However, no effect was seen on pro
      alpha 1(III) collagen mRNA levels.

PMID- 8575564
TI  - Acylfulvenes, a new class of potent antitumor agents.
AB  - Acylfulvene, derived from the sesquiterpene illudin S by treatment with acid
      (reverse Prins reaction), is far less reactive to thiols than illudin S. However,
      it is reduced readily to an aromatic product, in the same way as illudin S. This
      may explain its greatly improved therapeutic index compared to that of the parent
      compound.

PMID- 8575566
TI  - Advances in research and control of tuberculosis.

PMID- 8575565
TI  - Synthesis and cannabinoid receptor binding activity of conjugated triene
      anandamide, a novel eicosanoid.
AB  - A polyenoic fatty-acid isomerase (PFI) from a red marine alga was used to convert
      anandamide (5Z,8Z,11Z,14Z-eicosatetraenoyl-N-ethan olamide) to the 5Z,7E,9E,14Z
      eicosatetraenoyl-N-ethanol amide isomer. This novel eicosanoid, termed conjugated
      triene anandamide (CTA), was assessed for its ability to bind to the cannabinoid
      receptor in rat brain membrane preparations. CTA is a high affinity
      cannabimimetic substance whose novel structure provides new insight into
      structure-activity relationships of cannabinoid receptor ligands. These
      experiments illustrate the utility of enzymes isolated from marine organisms in
      the development of pharmacological probes.

PMID- 8575567
TI  - More on the noninvasive diagnosis of pulmonary hypertension: Doppler
      echocardiography revisited.

PMID- 8575568
TI  - Effect of erythromycin on Haemophilus influenzae endotoxin-induced release of IL
      6, IL-8 and sICAM-1 by cultured human bronchial epithelial cells.
AB  - Although several studies have demonstrated that low-dose, long-term erythromycin
      treatment is effective in the management of patients with chronic lower
      respiratory tract infections, such as chronic bronchitis, bronchiolitis and
      bronchiectasis, the mechanisms underlying the action of erythromycin are not
      clear. We have cultured human bronchial epithelial cells (HBEC) as explant
      cultures from surgical tissue, and have investigated the effect of erythromycin
      on H. influenzae endotoxin (HIE)-induced release of inflammatory mediators in
      these cultures. Confluent epithelial cell cultures were incubated with 100
      micrograms.mL-1 HIE +/- 0.1-10 micrograms.mL-1 erythromycin and were investigated
      for interleukin-6 (IL-6), interleukin-8 (IL-8) and soluble intercellular adhesion
      molecule-1 (sICAM-1) released into the culture medium after 24 h. HIE
      significantly increased the release of IL-6 from 3.9 +/- 1.5 pg.micrograms-1
      cellular protein (in control untreated cultures) to 12.1 +/- 1.5 pg.micrograms-1
      cellular protein, and IL-8 from 83.7 +/- 8.2 pg.micrograms-1 cellular protein (in
      control cultures) to 225.7 +/- 44.8 pg.micrograms-1 cellular protein. Similarly,
      HIE led to a significantly greater release of sICAM-1 from 0.04 +/- 0.01
      ng.microgram-1 cellular protein, in control cultures, to 3.8 +/- 0.9 ng.microgram
      1 cellular protein. Incubation of the epithelial cultures in the presence of 0.1
      10 micrograms.mL-1 erythromycin significantly blocked the HIE-induced release of
      IL-6, IL-8, and sICAM-1, at all concentrations of erythromycin investigated.
      Erythromycin also attenuated neutrophil chemotaxis and adhesion to human
      endothelial cells, mediated by incubation with conditioned medium obtained from
      HIE-exposed epithelial cell cultures, in vitro. These results suggest that H.
      influenzae-induced release of inflammatory mediators from airway epithelial cells
      could contribute to chronic airway inflammation, and that this effect may be
      modulated by treatment with erythromycin.

PMID- 8575569
TI  - Localization of neutral endopeptidase (NEP) mRNA in human bronchi.
AB  - Neutral endopeptidase (NEP) may regulate peptide-induced inflammation in the
      respiratory tract. It is of interest to determine which respiratory resident
      cells express NEP. Trachea and bronchi from seven nonsmoking, nonasthmatic
      subjects were examined. NEP messenger ribonucleic acid (mRNA) was characterized
      by Northern blot hybridization of cultured human tracheobronchial epithelial and
      smooth muscle cells, and reverse transcriptase-polymerase chain reaction (RT-PCR)
      in trachea and bronchi. In situ hybridization with biotin- and 35S-labelled
      antisense complementary ribonucleic acid (cRNA) probes was used to determine the
      distribution of NEP mRNA in human bronchial mucosa. NEP-immunoreactive material
      was detected using MEK10 murine monoclonal antibodies and the immunogold method
      with silver enhancement. NEP mRNA was 4.5 kb in size in the cultured human smooth
      muscle and epithelial cells by Northern blot analysis. No evidence was found by
      RT-PCR for truncated, alternatively spliced NEP mRNAs, such as del exon 16 or del
      exons 5-18 in human bronchus. NEP mRNA was detected by in situ hybridization in
      epithelial cells, submucosal glands, bronchial smooth muscle and endothelium. NEP
      immunoreactive material was identified in the epithelium, submucosal glands,
      bronchial smooth muscle, and endothelium, demonstrating an excellent correlation
      between the distribution of NEP mRNA and the cell surface protein. NEP mRNA and
      immunoreactive material were excluded from epithelial goblet cell and submucosal
      gland mucous cell vacuoles. We conclude that the various sites of NEP protein and
      mRNA expression correlate with the locations of peptide receptors and NEP enzyme
      function, and are consistent with the hypothesis that NEP may regulate peptide
      induced inflammation in human bronchi.

PMID- 8575570
TI  - Blood eosinophil leukotriene C4 production in asthma of different severities.
AB  - In asthma, activation and recruitment of eosinophils to the bronchial mucosa
      amplifies many cellular functions. The blood eosinophil count and the number of
      hypodense eosinophils increase with asthma severity. Eosinophils produce numerous
      proinflammatory mediators in response to a variety of agonists, notably the
      peptido-leukotriene (LT) C4, a potent bronchoconstrictor. In this study, we have
      evaluated blood eosinophil LTC4 release and its modulation by cytokines in normal
      individuals and in subjects with asthma of various severities: mild (beta 2
      agonist on demand); moderate (inhaled steroids on a regular basis); and severe
      (inhaled and oral steroids on a regular basis). Eosinophils were isolated using a
      modified Percoll gradient technique, which recovers both hypodense and normodense
      eosinophils in a global cell population. Eosinophils released detectable amounts
      of LTC4 only in the presence of the stimulus (calcium ionophore A23187, 2
      microM). The ionophore-induced LTC4 release was greater in moderate asthmatics
      (mean +/- SEM 5.7 +/- 1.3 pg x 10(3)/250,000 eosinophils) than in normal
      individuals (1.6 +/- 0.4 pg x 10(3)/250,000 eosinophils), mild asthmatics (1.8 +/
      0.3 pg x 10(3)/250,000 eosinophils) and severe asthmatics (2.0 +/- 0.3 pg x
      10(3)/250,000 eosinophils). Granulocyte/macrophage colony-stimulating factor (GM
      CSF) and interleukin-5 (IL-5) amplified the ionophore-induced LTC4 release in the
      four groups from 1.9 to 2.6 and 1.9 to 2.8 fold, respectively. Interleukin-3 (IL
      3) did not increase LTC4 production except by the eosinophils of the severe
      asthmatics whose ionophore-induced LTC4 production was enhanced by 1.9 fold.
      These data demonstrate that the asthmatic bronchial inflammatory process may
      modify blood eosinophil LTC4 release and its modulation by cytokines according to
      asthma severity and treatment.

PMID- 8575571
TI  - FK506 and cyclosporin A inhibit granulocyte/macrophage colony-stimulating factor
      production by mononuclear cells in asthma.
AB  - Bronchial asthma is associated with eosinophilic inflammation and expression of T
      cell-derived cytokines, which influence eosinophilic function. FK506, a newly
      established immunosuppressive agent, may have potential as a therapeutic
      instrument for asthma because of its suppressive effect on T-cell activation. To
      assess this, we compared the inhibitory effects of FK506 and cyclosporin A on
      production of granulocyte/macrophage colony-stimulating factor and interleukin-5
      by interleukin-2- or Dermatophagoides farinae-stimulated mononuclear cells from
      patients with asthma, and their contribution to proliferation and survival of
      eosinophils in vitro. FK506 inhibited granulocyte/macrophage colony-stimulating
      factor production by stimulated mononuclear cells from asthma patients at lower
      concentrations than cyclosporin A. Both drugs inhibited eosinophil proliferation
      and survival activity from mononuclear cells at comparable concentrations.
      Interleukin-5 production by stimulated mononuclear cells was also inhibited both
      by FK506 and cyclosporin A. We conclude that both FK506 and cyclosporin A have
      potential for therapy of bronchial asthma.

PMID- 8575572
TI  - In vivo study of indomethacin in bronchiectasis: effect on neutrophil function
      and lung secretion.
AB  - Bronchiectasis is associated with sputum containing high levels of the
      proteolytic enzyme elastase, which is thought to be involved in the pathogenesis
      of the disease. Agents which inhibit neutrophil function and interfere with
      neutrophil elastase release may have a beneficial effect on the development and
      progression of such diseases. We have studied the effects of the nonsteroidal
      anti-inflammatory agent indomethacin on neutrophil function in nine patients with
      clinically stable bronchiectasis. All patients remained clinically stable during
      the study. We observed a significant reduction in peripheral neutrophil
      chemotaxis to 10 nmol.L-1 N-formyl-methionyl-leucyl-phenylalanine (FMLP) from a
      mean of 19.86 (SEM 1.35) to 8.46 (0.68) cells.field-1 after 4 weeks of therapy.
      There was also a significant reduction in fibronectin degradation both by resting
      and FMLP-stimulated neutrophils, from a mean of 1.90 (0.19) micrograms x 3 x
      10(5) cells at the start of therapy to 0.87 (0.08) micrograms after 4 weeks, and
      from 3.17 (0.35) micrograms to 1.48 (0.05) micrograms, respectively. There was no
      effect on spontaneous or stimulated superoxide anion generation by neutrophils.
      Despite the marked changes in peripheral neutrophil function, no adverse effect
      was observed on viable bacterial load in the bronchial secretions. In addition,
      there was no difference in sputum albumin, elastase or myeloperoxidase levels,
      and only minor changes in the chemotactic activity of the sputum. These results
      suggest that nonsteroidal anti-inflammatory agents have a major effect on
      peripheral neutrophil function but do not appear to have an adverse effect on
      bacterial colonization of the airways.

PMID- 8575573
TI  - Effect of regular inhaled beclomethasone on exercise and methacholine airway
      responses in school children with recurrent wheeze.
AB  - The role of airway inflammation in the pathogenesis of asthma in childhood is
      uncertain. In the present study, 27 atopic and nonatopic children aged 7-9 yrs
      who had > or = 5 episodes of wheeze and symptoms of exercise-induced asthma (EIA)
      in the previous 12 months, performed a methacholine challenge and exercise test
      on separate days at monthly intervals. The subjects had not received oral or
      inhaled corticosteroids for 12 months prior to the study. The dose-response
      relationship to inhaled methacholine was expressed as the cumulative dose
      provoking a 20% decrease in forced expiratory volume in one second (PD20). Forced
      expiratory volume in one second (FEV1) and peak expiratory flow (PEF) were
      measured prior to the exercise test and at 0, 3, 5, 10, 15 and 20 min following
      maximal exercise. Following the first methacholine challenge and exercise test,
      the children were randomized in a double-blind manner to receive inhaled
      beclomethasone dipropionate (BDP) 200 micrograms b.i.d. or a placebo b.i.d. from
      a Diskhaler for 3 months. All children were asymptomatic at the time of testing,
      and there was no significant change in the baseline FEV1 of any subject prior to
      either challenge throughout the study period. When compared to placebo, the
      bronchial responsiveness to exercise and methacholine was significantly
      attenuated in the children who had received inhaled BDP for at least 1 month.
      There was no relationship between the bronchial responsiveness to methacholine
      and exercise. There was no significant difference in the bronchial responsiveness
      to either stimulus in the atopic and nonatopic children. The results of this
      study suggest that immunoglobulin E (IgE)- and non-IgE-mediated airway
      inflammation are important in exercise- and methacholine-induced
      bronchoconstriction in children with recurrent wheeze, although it is probable
      that different mechanisms are responsible.

PMID- 8575575
TI  - Prostanoids and cough response to capsaicin in asthma and chronic bronchitis.
AB  - Cyclooxygenase products are released by chronic airway inflammation. Our working
      hypothesis for the present study was that prostanoids augment airway cough
      sensitivity. The effects of a cyclooxygenase inhibitor, indomethacin (100 mg.day
      1 for 4 days), and a thromboxane synthesis inhibitor, OKY-046 (400 mg.day-1 for 4
      days), on cough response to inhaled capsaicin were examined in eight patients
      with asthma, 10 patients with chronic bronchitis, and 10 normal subjects.
      Capsaicin cough threshold, the lowest concentration of capsaicin eliciting five
      or more coughs, was measured as an index of airway cough sensitivity. In
      asthmatics, the cough thresholds with indomethacin treatment (15.7 (GSEM 1.38)
      microM) and OKY-046 (10.2 (GSEM 1.20) microM) were significantly greater than the
      value with placebo (6.05 (GSEM 1.25) microM). In patients with chronic
      bronchitis, the cough threshold was significantly greater with indomethacin (5.94
      (GSEM 1.50) microM) than with placebo (3.41 (GSEM 1.33) microM and OKY-046 2.97
      (GSEM 1.43) microM). In normal subjects, the capsaicin cough threshold was not
      altered by indomethacin or OKY-046 treatment. These results support our
      hypothesis and suggest that thromboxane A2 may be one of the cyclooxygenase
      products augmenting airway cough sensitivity in asthma, but not in chronic
      bronchitis.

PMID- 8575574
TI  - Salmeterol xinafoate in asthmatic patients under consideration for maintenance
      oral corticosteroid therapy. UK Study Group.
AB  - In severe chronic asthma, long-term oral steroids may be necessary to control
      symptoms. In patients in whom such treatment was under consideration, the
      efficacy and safety of salmeterol xinafoate 100 micrograms b.i.d. was
      investigated in a randomized, double-blind, placebo-controlled parallel-group,
      multicentre study. One hundred and nineteen chronic symptomatic asthmatics were
      randomized to receive either salmeterol, 100 micrograms b.i.d. (n = 55; baseline
      % predicted morning peak expiratory flow (PEF) 59%; forced expiratory volume in
      one second (FEV1) 66%) or placebo (n = 64; baseline % predicted morning PEF 63%;
      FEV1 66%) both via the Diskhaler. Morning and evening PEF and asthma symptoms
      were recorded in daily record booklets by the patient over a 12 week period. A
      significant improvement in morning PEF was achieved after 1 month in the
      salmeterol treated group; this persisted throughout the treatment period
      (estimated treatment difference 22 L.min-1). There was a significant increase in
      the proportion of symptom-free nights experienced by the salmeterol treated group
      (33 (SD 32) %) compared with placebo (13 (26) %), and a significant decrease in
      daily use of relief medication (mean decrease 5.1 (4.7) doses per day with
      salmeterol, 2.5 (4.0) doses with placebo). Both treatments were well-tolerated,
      with no evidence of any difference in the side-effects associated with beta 2
      agonists. In conclusion, the addition of salmeterol (100 micrograms daily) to the
      existing treatment of chronic asthmatics under consideration for maintenance oral
      corticosteroid therapy is well-tolerated, improves lung function and provides
      additional symptom control.

PMID- 8575576
TI  - Tiotropium bromide, a new long-acting antimuscarinic bronchodilator: a
      pharmacodynamic study in patients with chronic obstructive pulmonary disease
      (COPD). Dutch Study Group.
AB  - The objective of the present study was to investigate the dose-dependent
      bronchodilator efficacy and duration of action of the newly developed
      antimuscarinic agent tiotropium bromide in patients with chronic obstructive
      pulmonary disease (COPD). In a randomized, double-blind, placebo-controlled,
      crossover design, patients inhaled single doses of 10-80 micrograms tiotropium
      bromide and placebo, formulated in lactose powder capsules. The washout period
      between test doses was 72 h. Thirty five patients were enrolled in the trial (32
      males and 3 females; mean age 64 yrs). Baseline forced expiratory volume in one
      second (FEV1) (mean 1.34 L) was less than 65% of predicted and was < 70% of
      forced vital capacity (FVC). All subjects had a smoking history of more than 10
      pack-years. The mean reversibility of FEV1 after inhalation of 40 micrograms
      ipratropium bromide was 28%. Pulmonary function testing was performed before and
      at regular time intervals for up to 32 h after test drug administration. Compared
      to placebo, tiotropium bromide produced significant improvements in FEV1, FVC,
      peak expiratory flow rate (PEFR) and forced mid-expiratory flow (FEF25-75%). The
      bronchodilator response was almost immediate; peak improvement in FEV1 was
      reached 1-4 h after test drug inhalation, and the duration of action extended to
      32 h after the 20, 40 and 80 micrograms doses. A clear dose-response relationship
      was seen for peak FEV1 and for the average FEV1 over differing time periods
      during the 32 h observation period, 80 micrograms of test drug being superior to
      the 10 micrograms dose. Peak improvement in FEV1 ranged 19-26% of test-day
      baseline for tiotropium bromide doses compared to 16% for placebo. The large
      improvement for placebo is probably due to carry-over effect which was
      significant. After excluding carry-over effect, the peak response to placebo
      decreased to 11%, whilst for tiotropium bromide doses it ranged 20-25%; standard
      error for mean difference was about 4%. There was no evidence of systemic
      anticholinergic effects. In this population of patients with COPD, tiotropium
      bromide was found to be a safe and long-acting bronchodilator, demonstrating a
      clear dose-response relationship following single dose administration.

PMID- 8575578
TI  - Occupational asthma in aluminium potroom workers related to pre-employment
      eosinophil count.
AB  - Occupational asthma still occurs in aluminium potroom workers despite pre
      employment medical selection. The purpose of our study was to identify workers
      with an increased risk of developing "potroom asthma". A nested, case-control
      study was carried out in two Dutch aluminium producing plants. Pre-employment
      data of 364 potroom workers (182 cases and 182 controls) were analyzed. Cases
      were workers unable to work because of work-related respiratory disease, meeting
      the criteria for potroom asthma. The selected controls were matched for age, year
      of starting employment and working conditions. Pre-employment eosinophil count
      was significantly related to the occurrence of potroom asthma, even though the
      mean number of the eosinophils in cases was within the normal range (< 275
      cells.mm-3; 0.28 cells x 10(9).L-1). Hence, 39 of the 45 individuals with blood
      eosinophil counts in the upper range of normal (> 220 cells.mm-3; 0.22 cells x
      10(9).L-1) developed potroom asthma with time. We conclude that workers without
      respiratory symptoms, with normal lung function and normal bronchial
      responsiveness before employment developed potroom asthma. Fluoride exposure,
      combined with an elevated eosinophil count, might induce an immunological or
      cytotoxic process.

PMID- 8575577
TI  - Allergic sensitization is associated with increased bronchial responsiveness: a
      prospective study of allergy to laboratory animals.
AB  - The purpose of this prospective study was to investigate the extent of change in
      bronchial responsiveness and the prognostic value of methacholine provocation in
      early sensitization to laboratory animals. Thirty eight laboratory technicians
      were studied during training (before first exposure) and after having been
      exposed to laboratory animals for a median 18 (range 5-33) months. On both
      occasions they were subjected to spirometry, bronchial methacholine challenge,
      skin-prick tests and blood sampling, and responded to questionnaires. Nine (24%)
      developed laboratory animal allergy (LAA), defined as animal work-related
      symptoms (n = 8), or specific immunoglobulin E (IgE) (n = 7) or both. In the LAA
      group, bronchial responsiveness was normal before employment, but had increased
      significantly at follow-up compared to technicians who had not developed LAA. Six
      of the nine LAA subjects had a more than threefold increase in bronchial
      responsiveness, and three of these reported chest symptoms. Spirometric values
      were not different between the groups prior to exposure or at follow-up, and had
      no prognostic value. However, a pre-employment level of total IgE > 100 kU.L-1
      predicted the development of LAA (relative risk 2.8). Thus, early LAA was
      associated with increased bronchial responsiveness in most subjects. In contrast
      to total IgE, the level of pre-employment bronchial responsiveness or lung
      function did not influence the magnitude of change in responsiveness, nor predict
      sensitization.

PMID- 8575579
TI  - Pressure-volume analysis of the lung with an exponential and linear-exponential
      model in asthma and COPD. Dutch CNSLD Study Group.
AB  - The prevalence of abnormalities in lung elasticity in patients with asthma or
      chronic obstructive pulmonary disease (COPD) is still unclear. This might be due
      to uncertainties concerning the method of analysis of quasistatic deflation lung
      pressure-volume curves. Pressure-volume curves were obtained in 99 patients with
      moderately severe asthma or COPD. These patients were a subgroup from a Dutch
      multicentre trial; the entire group was selected on the basis of a moderately
      lowered % predicted forced expiratory volume in one second (FEV1), and a
      provocative concentration of histamine producing a 20% decrease in FEV1 (PC20) <
      8 mg.mL-1 obtained with the 2 min tidal breathing technique. The curves were
      fitted with an exponential (E) model and an exponential model which took the
      linear appearance in the mid vital capacity range into account (linear
      exponential (LE)). The linear-exponential model showed a markedly better fit
      ability, yielding additional parameters, such as the compliance at functional
      residual capacity (FRC) level as slope of the linear part (b), and the volume at
      which the linear part changed into the exponential part of the curve (transition
      volume (Vtr)). Vtr (mean value Vtr/total lung capacity (TLC) = 0.79 (SD 0.07))
      showed a close positive linear correlation with obstruction and hyperinflation
      variables, which might be due to airway closure, already starting at elevated
      lung volumes. The exponential shape factor K was closely correlated with b and
      mean values (K = 1.32 (SD 0.05) kPa-1; b = 2.96 (SD 1.16) L,kPa-1) and the
      relationship with age was comparable with data reported in healthy individuals.
      The shape factor of the linear-exponential fit showed no correlation with any
      elasticity related variable. Neither the elastic recoil at 90% TLC, as obtained
      from the linear-exponential fit, nor its relationship with age were significantly
      different from healthy individuals. We conclude that, for a more accurate
      description of the lung pressure-volume curve, a linear-exponential fit is
      preferable to an exponential model. However, the physiological relevance of the
      shape parameter (KLE) is still unclear. These results indicate that patients with
      moderately severe asthma or COPD had, on average, no appreciable loss of elastic
      lung recoil as compared with healthy individuals.

PMID- 8575580
TI  - The effect of lung volume on transdiaphragmatic pressure.
AB  - Diaphragm strength can be assessed by measurement of transdiaphragmatic pressure
      (Pdi) in response to stimulation of the phrenic nerves. The length-tension
      relationship of the diaphragm can be studied by measuring twitch Pdi over the
      range of lung volume. Previous studies of the relationship between lung volume
      and diaphragm strength have used the technique of electrical stimulation of the
      phrenic nerves. In these studies, the phenomenon of twitch potentiation has not
      been taken into account. It has previously been shown that prior contraction of
      the diaphragm can greatly enhance the twitch response, thus affecting the
      measurements. The aim of this study was to investigate the relationship between
      unpotentiated twitch Pdi and lung volume for volumes ranging from residual volume
      (RV) to total lung capacity (TLC) in normal subjects. Great care was taken to
      avoid muscle potentiation. For this purpose, we stimulated the phrenic nerves
      with a magnetic stimulator. In addition, we used positive pressure to inflate the
      lungs to high lung volumes. The impact of twitch potentiation on the length
      tension relationship was investigated by subjects making maximum inspiratory
      efforts prior to phrenic nerve stimulation. The unpotentiated twitch Pdi
      decreased in a linear fashion with increasing lung volume over the full range of
      vital capacity by 0.54 kPa.L-1. Potentiation increased twitch Pdi by 40% at FRC
      and the effect was similar, in absolute terms, at all lung volumes. In relative
      terms, the effect of potentiation became greater as lung volume increased, and
      more than doubled twitch Pdi at TLC. With increasing lung volume, there is a
      linear fall in unpotentiated twitch Pdi with a slope that is less steep, over the
      same range of absolute lung volume, than previously reported. When assessing
      diaphragm strength by the twitch technique, it is essential to control for lung
      volume and equally important to control for twitch potentiation.

PMID- 8575581
TI  - Electrically-activated dilator muscles reduce pharyngeal resistance in
      anaesthetized dogs with upper airway obstruction.
AB  - There is current controversy as to whether electrical stimulation of upper airway
      musculature can be used us a beneficial treatment modality in patients with
      obstructive sleep apnoea syndrome. Increased upper airway (UAW) muscle activity
      decreases UAW resistance (Ruaw) in isolated UAW of dogs. In the present study, we
      evaluated the effect of UAW muscle contraction on UAW patency in anaesthetized
      dogs in vivo breathing spontaneously through partially and completely obstructed
      UAW. Airflow and supraglottic pressure were measured to obtain Ruaw. Ruaw could
      be regulated by inhalation of a rubber balloon implanted transcutaneously in the
      pharyngeal submucosa to produce partial or complete obstruction. Wire electrodes
      were implanted bilaterally into the genioglossus (GG), geniohyoid (GH),
      sternothyroid (ST), and sternohyoid (SH) muscles for electrical stimulation (ES),
      and into the alae nasi for electromyographic (EMG) recording. Three levels of
      electrical stimulation were delivered to each muscle before and during partial or
      complete UAW obstruction. Genioglossus and geniohyoid stimulation both resulted
      in a significant reduction in Ruaw, which was most pronounced during partial
      obstruction, reducing Ruaw from 54 +/- 11 to 14 +/- 3 and from 74 +/- 12 to 31 +/
      5 cmH2O.L-1.s, respectively. At low voltage, stimulation of the genioglossus was
      more effective than stimulation of the geniohyoid in reducing Ruaw. Furthermore,
      electrical stimulation of the genioglossus but not of the geniohyoid released
      total obstruction. In contrast, electrical stimulation of the sternohyoid and
      sternothyroid produced no significant change in Ruaw. These findings demonstrate
      that selective UAW dilatory muscle contraction in spontaneously breathing
      anaesthetized dogs reduces Ruaw in the presence of UAW obstruction and releases
      UAW occlusion, with the genioglossus being the most effective muscle. This
      favours further attempts to investigate the benefits of electrical stimulation of
      selected upper airway muscles in the treatment of obstructive sleep apnoea
      syndrome.

PMID- 8575582
TI  - Risk factors for the development of Haemophilus influenzae pneumonia in
      hospitalized adults.
AB  - Potential risk factors for developing Haemophilus influenzae nosocomial pneumonia
      have not been sufficiently studied. We wanted to investigate the incidence and
      risk factors for the development of Haemophilus influenzae pneumonia in the
      hospital by means of a multivariate analysis. A total of 468 cases of nosocomial
      pneumonia were observed during the study period, 317 (68%) of which were
      aetiologically diagnosed by means of highly reliable methods, and H. influenzae
      was isolated in 57 of them. Fifty of the 57 episodes of H. influenzae pneumonia
      occurred in mechanically-ventilated patients. Underlying diseases were: medical
      in 12 cases, surgical in 15 cases, and traumatological in 22. Variables
      associated with Haemophilus influenzae nosocomial pneumonia in intubated patients
      after the univariate analysis were: "period between admission and pneumonia 2-7
      days" and "no previous antibiotics". A multivariate analysis demonstrated that
      the variables "no previous antibiotics" and "coma on admission" were risk factors
      for H. influenzae pneumonia. In nonintubated patients, no risk factors were found
      for H. influenzae pneumonia compared with other nosocomial pneumonia. We conclude
      that H. influenzae was involved in 57 out of 317 (18%) of nosocomial pneumonia
      registered in our institution, and the majority of patients (50 out of 57) were
      mechanically-ventilated. In this particular subgroup, coma of the patient on
      admission to hospital and absence of antibiotic treatment prior to developing
      pneumonia constitute two definite risk factors for developing H. influenzae
      nosocomial pneumonia.

PMID- 8575584
TI  - Cost-analysis of four diagnostic strategies for Pneumocystis carinii pneumonia in
      HIV-infected subjects.
AB  - The aim of this study was to analyse the cost-effectiveness ratio of four
      diagnostic strategies for Pneumocystis carinii pneumonia (PCP) in patients
      infected with human immunodeficiency virus (HIV). Two hundred and ten HIV
      infected patients with suspected PCP underwent induced-sputum (IS) followed, if
      negative, by bronchoalveolar lavage (BAL); 85 of these patients were able to
      undergo an exercise test (ET), prior to induced sputum and BAL. The following
      strategies were analysed: BAL strategy (BAL whenever PCP is suspected); IS
      strategy (induced sputum followed by BAL if negative); exercise test (ET)
      strategy, (ET followed by BAL if the results are abnormal); and the ES (exercise
      sputum) strategy (i.e. BAL only after abnormal ET and negative IS). The cost of
      each strategy was calculated by taking into account only direct costs; the
      conditions in which two given strategies would be cost-equivalent were also
      evaluated. The prevalence of PCP in this population was 31%; IS had 100%
      specificity and 71% sensitivity, whilst ET had 100% sensitivity and 77%
      specificity. The costs of BAL, IS, ET and ES strategies were 210,000, 191,940,
      140,700 and 112,700 FF, respectively. The ES strategy is, thus, most suitable for
      our unit. The most economic strategy depends not only on the cost and
      characteristics of the procedures, but also on the prevalence of PCP in the test
      population. In conclusion, we developed a model for use by diagnostic centres in
      choosing the most suitable strategy, on the basis of the local prevalence of PCP.

PMID- 8575583
TI  - Clinical characteristics and outcome of Pneumocystis carinii pneumonia in HIV
      infected and otherwise immunosuppressed patients.
AB  - The factors contributing to unequal mortality rates following Pneumocystis
      carinii pneumonia (PCP) in different groups at risk are poorly understood. We
      therefore compared the first episodes of PCP without prophylaxis in human
      immunodeficiency virus infected (HIV) and otherwise immunosuppressed patients in
      this retrospective study. A total of 58 HIV-infected and 16 otherwise
      immunosuppressed patients were analysed. The comparison included epidemiological,
      clinical, laboratory, radiological and microbiological data, as well as therapy
      and clinical course. A prognostic analysis was performed using a logistic
      regression model. The mortality was significantly different in the two groups
      (HIV group 17 versus non-HIV group 50%). Renal transplant patients had a higher
      survival rate as compared to malignancy or collagen vascular disease as
      underlying diseases at risk. Acute respiratory failure was more common in the non
      HIV group. Variables found to be significantly associated with lethal outcome in
      univariate analysis were alveolar to arterial pressures difference for oxygen
      (P(A-a),O2), haemoglobin, platelet count, total protein, serum albumin, and gamma
      globulins in the HIV-group, and serum albumin in the non-HIV group. In the
      multivariate analysis of the HIV group, platelet count and gamma-globulins
      remained independent prognostic factors. In conclusion, in the HIV-group,
      mortality is closely related to the severeness of PCP as well as to the
      severeness of the acquired immune deficiency syndrome (AIDS) disease. In the non
      HIV group, malignancy and collagen vascular disease as underlying conditions at
      risk account for the high mortality rate. Its severeness was mainly reflected by
      serum albumin, which represented the only variable found to be significantly
      associated with death in both groups.

PMID- 8575585
TI  - Predictive value of serum III procollagen for diagnosis of pulmonary involvement
      in patients with scleroderma.
AB  - High resolution computed tomography (HRCT) was recently demonstrated to be as
      good as open lung biopsy for the diagnosis of pulmonary involvement in patients
      with scleroderma. Nevertheless, in view of its price and related irradiation,
      HRCT cannot be recommended as a screening test. Serum III procollagen (sPIIINP)
      is an aminopropeptide of type III collagen, which is released during conversion
      into collagen by specific proteases. Increased levels of sPIIINP have been
      observed in patients with scleroderma. The aim of the present study was to assess
      the relationship between sPIIINP measurement and pulmonary involvement defined
      according to HRCT and pulmonary function tests (PFT) with single-breath carbon
      monoxide transfer capacity (TL,CO) in 28 patients suffering from scleroderma.
      Patients were divided into two groups for analysis, Group A comprising 16
      patients without pulmonary scleroderma and Group B comprising 12 patients with
      pulmonary scleroderma. All patients had stable cutaneous disease and normal renal
      and hepatic function. The level of sPIIINP was determined by radioimmunoassay
      (RIA-gnost P-III-P, Prod. Nr. ODMT; Behring, Marburg, Germany). Mean +/- SD
      sPIIINP level in Group A was 0.85 +/- 0.21 U.mL-1. Individual values ranged 0.6
      1.3 U.mL-1. Mean +/- SD sPIIINP value was 1.30 +/- 0.40 U.mL-1 in Group B and
      individual values ranged 0.7-1.9 U.mL-1. The difference in mean sPIIINP level
      between Group A and Group B was significant. Using a cut-off at 1.1 U.mL-1,
      sensitivity of sPIIINP was 0.66, specificity 0.94, positive predictive value
      0.89, negative predictive value 0.79, false positive rate 0.06, and false
      negative rate 0.33. The value of sPIIINP correlated with HRCT score but not with
      PFT. This study confirms the relationship between sPIIINP and scleroderma with
      interstitial lung disease. We suggest that sPIIINP could be measured in patients
      with scleroderma to screen those patients requiring HRCT. Further studies are
      necessary to determine the value of sPIIINP in terms of prognosis and follow-up
      of patients under treatment.

PMID- 8575586
TI  - Blood cell redistribution in the lung after administration of recombinant human
      granulocyte-macrophage colony-stimulating factor.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF), in addition to being a
      haematopoietic growth factor, has been shown to stimulate in vitro the production
      of interleukins 1, 6 and 8 (IL-1, IL-6 and IL-8), tumour necrosis factor-alpha
      (TNF-alpha) and GM-CSF by polymorphonuclear cells (PMNs), alveolar macrophages
      (AMs), fibroblasts and endothelial cells of the lung, and the growth and
      differentiation of resident alveolar macrophages. The aim of this study was to
      establish whether recombinant GM-CSF (rhGM-CSF), administered subcutaneously at a
      dose of 5 micrograms.kg-1 for 3 days in five patients with unresectable non-small
      cell lung cancer before starting chemotherapy, induces an increase in the
      alveolar cell count, and whether these cellular lung variations may be related to
      increases in the above-mentioned cytokines. In the bronchoalveolar lavage fluid
      (BALF) total cell count, polymorphonuclear cells, neutrophils, and alveolar
      macrophages increased significantly in comparison with the baseline, and the
      extent of variation of the BAL cell count was considerably greater than that of
      the circulating leucocytes. The mean levels of all the cytokines increased, but a
      significant difference with respect to the basal condition was observed only for
      IL-6 and IL-8. After rhGM-CSF treatment, significant correlations were found
      between neutrophil counts and the levels of IL-6 and IL-8. In conclusion, rhGM
      CSF administration induces a cellular expansion in the lung, and the neutrophil
      increase appears to be related to increased levels of IL-8.

PMID- 8575587
TI  - Manifestations and consequences of obstructive sleep apnoea.
AB  - Over the last two decades the diagnostic tools used in sleep medicine have
      developed enormously, making it possible to study the interaction of sleep
      related breathing disorders (SRBD) with cardiovascular function and the autonomic
      nervous system, as well as the effects of SRBD on a variety of physiological
      processes during wakefulness. Different modes of nasal ventilation are now
      available, allowing all forms of SRBD to be treated. If early diagnosis and
      treatment are provided, the acute and long-term sequelae of SRBD can be
      prevented. In addition to the care and treatment of patients with severe
      obstructive sleep apnoea syndrome (OSAS), future patient management will need to
      focus on patients with milder forms of obstructive sleep apnoea (OSA). In
      particular, the consequences of SRBD on cardiac arrhythmias, arterial
      hypertension and hypersomnolence are discussed, considering epidemiological,
      clinical, diagnostic and therapeutic aspects. Some economical issues arising from
      SRBD are also discussed, and the authors conclude that a Europewide programme for
      early detection, treatment and prevention of SRBD is required. This could make a
      large contribution to the reduction of cardiovascular morbidity and mortality and
      also reduce the incidence of "human error catastrophes" due to hypersomnolence.

PMID- 8575588
TI  - Physical examination of the adult patient with respiratory diseases: inspection
      and palpation.
AB  - Inspection of the thorax identifies the breathing position adopted by the
      patient, the shape of the thorax, the dynamics of respiration (breathing pattern,
      symmetry of expansion, mechanics and synchrony of rib cage and abdominal
      movements). Inspection of the neck adds useful information, particularly with
      respect to the dynamics of breathing. Palpation ascertains the signs suggested by
      inspection with respect to the mechanics of breathing. It also assesses the state
      of the pleura and pulmonary parenchyma by studying the tactile fremitus. It
      integrates extrarespiratory signs, such as enlarged lymph nodes or breast
      abnormalities. Extrathoracic respiratory signs should also be systematically
      looked for, including cyanosis, finger deformation, pulsus paradoxus, and pursed
      lips breathing. Interobserver agreement about respiratory signs has repeatedly
      been studied, and generally found to be low, as are clinical-functional
      correlations. However, some data on chronic obstructive pulmonary disease (COPD),
      asthma or pulmonary embolism are available. From the description of some signs
      and the current knowledge about their operative values, it appears that much
      clinical research remains necessary to better define the precise diagnostic value
      of a given sign. The impact of training on diagnostic performance also has to be
      defined. Both of these aspects should allow clinicians to optimize the way in
      which they use their hands and eyes to conduct respiratory diagnosis, as well as
      the way they teach respiratory symptomatology.

PMID- 8575589
TI  - Inhalation of antibiotics in cystic fibrosis.
AB  - Aerosol administration of antipseudomonal antibiotics is commonly used in cystic
      fibrosis. However, its contribution to the improvement of lung function,
      infection and quality of life is not well-established. All articles published
      from 1965 until the present time concerning the inhalation of antibiotics in
      cystic fibrosis were collected by computerized literature search and analysed.
      Effective aerosol delivery is compromised by nebulizers with limited capacity to
      produce particles in the respirable range. Twelve studies concerning maintenance
      treatment were published. Four uncontrolled studies evaluating antibiotic aerosol
      maintenance treatment in stable patients indicated a beneficial effect in terms
      of reducing the number of hospital admissions. Eight placebo-controlled studies
      were found; six of these showed a significant improvement of lung function in the
      treatment group. Four studies showed a reduction of the number of hospital
      admissions. In some studies, there was a considerable negative effect of the
      nebulized placebo solution on the outcome, probably due to the improper choice of
      its osmolarity. Studies with antibiotic aerosols as adjunct to intravenous
      therapy in cystic fibrosis patients with an acute exacerbation showed no
      enhancement of the clinical effects of the intravenous antibiotic by the aerosol;
      sputum colony counts, however, were lower. Toxicity studies carried out so far
      have shown no renal or ototoxicity; however, long-term toxicity studies still
      have to be performed using higher dosages. Introduction or selection of resistant
      bacteria is relatively rare, but remains a matter of concern. Aerosol maintenance
      treatment with an appropriate antibiotic in high enough dosage can be recommended
      for patients with cystic fibrosis chronically infected with P. aeruginosa, and
      may improve lung function and reduce the number of hospital admissions due to an
      acute exacerbation.

PMID- 8575590
TI  - Statement on self-monitoring of peak expiratory flows in the investigation of
      occupational asthma. Subcommittee on Occupational Allergy of the European Academy
      of Allergology and Clinical Immunology. American Academy of Allergy and Clinical
      Immunology. European Respiratory Society. American College of Allergy, Asthma and
      Immunology.

PMID- 8575591
TI  - Spontaneous haemopneumothorax: a surgical emergency.
AB  - We describe two cases of spontaneous haemopneumothorax treated successfully at
      emergency thoracotomy. We emphasize the importance of torn apical vascular
      adhesions as a source of intrathoracic haemorrhage in these two cases.

PMID- 8575592
TI  - Idiopathic lobular panniculitis with specific pleural involvement.
AB  - A 19 year old man presented with fever and left pleural effusion. Biopsy of a
      subcutaneous nodule and bone marrow led to the diagnosis of idiopathic lobular
      panniculitis (Weber-Christian disease). Thoracoscopically guided biopsy of the
      visceral pleura also revealed panniculitis change in the pleural adipose tissue.

PMID- 8575593
TI  - Epithelioid haemangioendothelioma of the lung: clinical and pathological
      pitfalls.
AB  - In 1973, a 10 year old boy presented with numerous bilateral lung nodules,
      diagnosed as histiocytosis X by open lung biopsy. The patient was treated with
      prednisone until 1984. In 1993, he developed severe pain in the neck. A biopsy of
      the spine revealed the same tumour morphology as was seen in the lung in 1973.
      Immunohistological examination of the former and present biopsy led to the
      definitive diagnosis of epithelioid haemangioendothelioma of the lung with
      metastases to spine and liver. Epithelioid haemangioendothelioma of the lung is a
      rare soft tissue tumour of vascular origin, readily mistaken for carcinoma or, as
      in this case, histiocytosis. The tumour has an intermediate malignant potential.
      Although metastases of epithelioid haemangioendothelioma of the lung are well
      known, metastatic spread to bones, as in our case, has not previously been
      mentioned in the literature.

PMID- 8575594
TI  - Pulmonary fibrosis and sea-blue histiocyte infiltration in a patient with primary
      myelofibrosis.
AB  - The authors present the case of a 73 year old man with primary myelofibrosis,
      pulmonary fibrosis, and acquired sea-blue histiocytosis, who died of respiratory
      failure. Pathology of the lungs revealed infiltration by sea-blue histiocytes,
      and fibrosis in the alveolar septa, and clumps of these cells filling the
      alveolar spaces. Megakaryocytes were also occasionally observed in the alveolar
      capillaries.

PMID- 8575595
TI  - Expiratory flow limitation during tidal breathing.

PMID- 8575596
TI  - Flow-limitation and upper airways.

PMID- 8575597
TI  - Rapid chest compression and flow limitation.

PMID- 8575598
TI  - Research of the exploitation of human resources in blind prevention and primary
      eye care.
AB  - PURPOSE: This research studied how to establish a relatively advanced blindness
      prevention and eye care cause in economically underdeveloped countryside.
      METHODS: Ophthalmic vocational schools and professional lectures were held to
      train "practical type" primary eye care workers for the countryside. Further
      study in high-level (above provincial) hospitals was taken to train blindness
      prevention & eye care backbones and leaders. RESULTS: In 1986, the ratio of the
      number of the eye care workers of all levels to the number of the whole
      population in the prefecture was 1:26,000. In 1992, it rose to 1:17,000. An eye
      care network of 222 stations had been established in the countryside. Ten in the
      13 county hospitals had a seperated ophthalmology department, in which 3 were
      awarded "National advanced blindness prevention County". Twenty one hospitals
      were appointed as the Unit of Surgical Vision-Rehabilitation of Cataract.
      Blindness prevention and eye care covered 1,000,000 population (eye care
      available within 5 kilometers), 23.5% of the whole population. CONCLUSIONS: In a
      demographically large but economically underdeveloped countryside area, the key
      to wide-range blindness prevention and eye care is to exploit human resources
      effectively. We should train "Practical type" primary eye care workers, and have
      a number of department leaders who are authoritive, influential in this field and
      ready to sacrifice to this cause.

PMID- 8575599
TI  - Characteristics of an established retinoblastoma cell line HXO-Rb44.
AB  - PURPOSE: To study the retinoblastoma cell culture and to establish a new
      retinoblastoma cell line. METHODS: 22 retinoblastomas were cultured by using the
      method of single cell suspension. Characteristics of the cultured cells were
      studied in the following programs: tumor cell morphology in vitro, electron
      microscopic, growth curve, cloning in soft agar, immunohistochemistry, karyotype
      and tumorigenicity. RESULTS: 22 retinoblastomas were cultured successfully in
      vitro, only a continued cell line HXO-Rb44 was established (more than 3 years).
      The characteristics of this cell line are that it grew as a suspension of round
      cell in graps like clusters in vitro, its population doubling time was 44 hours,
      and it could be cloned in soft agar. Histopathologic and ultrastructured pictures
      showed the characteristics of Rb. HXO-Rb44 cell was positive to NSE and negative
      to GFAP in immunohistochemical staining. A subcutaneous injection of HXO-Rb44
      cells produced a retinoblastoma in BALB/C athumic nude mice. CONCLUSIONS: HXO
      Rb44 has the characteristics of retinoblastoma and is a new retinoblastoma cell
      line. It is a useful material for study this tumor both in basic and clinical
      fields.

PMID- 8575600
TI  - A study of immunoactivity of retinal S-antigen in retinoblastoma.
AB  - PURPOSES: To study retinal S-antigen expression in human retinoblastoma and
      assess if there is a correlation between S-antigen immunoactivity and degree of
      retinoblastoma cell differentiations. METHODS: Ten cases of Chinese
      retinoblastoma parafin-embedded tissues were applied for this study. A strain of
      monoclonal antibody,MabA9C6, which defines an epitope in S-antigen retained in
      fixed-tissue sections, was used to study S-antigen expression in 10 cases of
      retinoblastomas. S-antigen was localized by the biotinavidin indirect
      immunoperoxidase technique and purified MabA9C6 ascites fluid was used with 1:100
      dilution. The whole procedure could be finished within a few hours. RESULTS: The
      S-antigen immunoactivity was observed in different patterns: the "normal"
      photoreceptor elements incorporated in 3 cases of growing tumors; 3 of 4
      Fleurettes and E-W rosettes; and scattered tumor cells in 50% of the cases.
      CONCLUSIONS: The result suggests that the expression of S-antigen in
      retinoblastoma may be used to assess the degree of tumor differentiation as
      another tumor marker in retinoblastoma.

PMID- 8575601
TI  - Modified vitreous surgery for subretinal neovascularization and hemorrhage.
AB  - PURPOSE: To modify vitreous surgery for subretinal neovascularization (SRNV) and
      to determine the effects of this operation. METHODS: Six patients with SRNV were
      performed with this operation. The methods of examination before and after
      operation included: testing the best-corrected visual acuity before operation and
      1, 3 or 6 months after operation; 30 degrees and macular 10 degrees Humphrey
      visual field examination; FFA examination preoperatively and 1, 3 or 6 months
      postoperatively. Modified surgery procedure is: a preventive buckling; pars plana
      vitrectomy; peeling the vitreous cortical; no intraocular diathermy; small
      retinotomy; subretinal surgery; air-fluid exchange. RESULTS: SRNV was taken off
      in 4 cases. Subretinal hemorrhage was washed in 2 cases. After 4 to 7 months
      follow-up, the visual acuity was improved in 4 cases, unchanged in 2 cases. The
      visual field was improved in 4 cases, unchanged in 1 case, decraesed in 1 case.
      The complications included macular hole due to surgery in 1 case and subretinal
      hemorrage in 1 case. CONCLUSION: The surgery criteria were: 1) massive subretinal
      hemorrhage; 2) some patients of SRNV included: FFA evidence they showed the
      membrane is beneath fovea, the best V. A is 20/100 or lower, and can't be treated
      by laser and the patient consent. This modified subretinal operation is safe, and
      effective for massive hemorrhage and some SRNVS.

PMID- 8575602
TI  - Repetitive, low-dose tissue plasminogen activator for clearance of experimental
      vitreous hemorrhage.
AB  - PURPOSE: To investigate the effectiveness of repetitive, low-dose tPA for
      clearance of experimental vitreous hemorrhage. METHODS: The model vitreous
      hemorrhage was produced by intravitreal injection of 0.05ml of autologous
      citrated whole blood in 14 rabbits (28 eyes). One week after the creation of
      vitreous hemorrhage, the eyes were randomly separated into 3 groups. Groups 1 and
      2 received two injections of 5 or 25 micrograms of tPA, respectively, with one
      injection in a 7-day interval. Group 3 received two injections of PS in the same
      way. RESULTS: The clearance of vitreous hemorrhage in tPA-treated groups was
      significantly faster than that in the control group (P < 0.05, or P < 0.01).
      However, there was no statistically significant difference between the two tPA
      treated groups. Not any retinal toxicity was detected by ERG, light microscopy,
      and transmission electron microscopy examinations. CONCLUSIONS: Repetitive
      injections of low-dose tPA were effective in the treatment of experimental
      vitreous hemorrhage. Whether it is effective on the clearance of vitreous
      hemorrhage in human eyes needs further investigation.

PMID- 8575603
TI  - Proliferative inhibition of rabbit lens epithelial cell--preliminary
      investigation for prevention of after cataract.
AB  - PURPOSE: To study the ability of Homoharringtonine (Hh), 5-Fluorouracil (5-Fu),
      and Adriamycin (ADM) on inhibiting the proliferation of rabbit lens epithelium.
      METHODS: Whole rabbit lenses were removed from freshly enucleated eyes under
      sterile condition. The rabbit lens epithelia (RLE) were isolated and cultured:
      (1) The passage RLE were placed in 24-well tissue culture plates and incubated
      for 48 hours, then exposed to different concentrations of Hh, 5-Fu, and ADM for
      24 and 72 hours; (2) The passage RLE and Hh (0.084 microgram/ml), 5-Fu (0.058
      microgram/ml), ADM (0.45ng/ml) were placed and cultured for 24 hours; (3) The
      morphological changes of RLE exposed to different concentrations of Hh, 5-Fu and
      ADM were studied under light microscope. RESULTS: The ID50 of Hh, 5-Fu and ADM
      exposed to RLE for 24 hours were 0.84 microgram/ml, 0.58 microgram/ml and
      4.50ng/ml, respectively, and those for 72 hours were 0.49 microgram/ml, 0.33
      microgram/ml and 3.85ng/ml. The attachment rate of RLE after being cultured for
      24 hours with Hh, 5-Fu and ADM were respectively 83.6%, 89.1% and 87.3%. The
      morphological changes of RLE demonstrated that obvious changes in the cell
      membrane and cytoplasm were found even in lower concentration, but changes in the
      nuclei could only be found in higher concentration of these drugs. CONCLUSION: Hh
      can not only inhibit the proliferation of RLE but also reduce the number of
      attached cells. It is suggested that Hh may be more useful for the prevention of
      after cataract than 5-Fu and ADM.

PMID- 8575604
TI  - The relation of the location of haptics of posterior chamber intraocular lenses
      and peripheral anterior synechia.
AB  - PURPOSE: To investigate the occurrence, outcome and influencial factors of the
      peripheral anterior synechia (PAS) following implantation of posterior chamber
      intraocular lenses for finding a way to reduce the PAS. SUBJECTS: 40 eyes of 38
      senile cataract patients with normal chamber angle and intraocular pressure (IOP)
      preoperatively were examined. METHODS: Extracapsular cataract extraction was
      performed under microscope with insertion of a posterior chamber lens implant
      vaulted anteriorly by 10 degrees. Gonioscopy and slit-lamp examination and
      photography of the operated eyes were performed 3 to 6 months postoperatively.
      RESULTS: PAS were found in 20 (50%) of the 40 eyes. Among the 20 eyes with PAS
      the locations of 23 haptics in 17 eyes corresponded with those of the PAS. PAS
      were seen more frequently with vertically sulcus-fixated haptics than with the
      horizontally capsular-fixated haptics, showing a significant difference (P <
      0.05). 88% of the eyes with PAS had pupillary deformation, but their visual
      acuities and IOP were not affected. CONCLUSIONS: PAS is more likely to occur with
      vertically sulcus-fixated IOL. Rotating the capsular-fixated haptics to the
      horizontal position may reduce the incidence of PAS. Gonioscopy should be a
      routine follow-up examination.

PMID- 8575605
TI  - Effect of Chinese medicines on the subretinal fluid absorption after operation
      for retinal detachment.
AB  - PURPOSE: To determine the effects of traditional Chinese medicines on subretinal
      fluid absorption after Operation for retinal detachment. METHODS: Among 100 eyes
      with operations for retinal detachment without drainage of fluid, there were 50
      eyes in traditional Chinese medicine treatment group and 50 eyes in the control
      group, and there were no significant difference between the two groups in age,
      myopia and retinal detachment area. We observed the time for the absorption of
      subretinal fluid and visual acuity improvement after the operations for retinal
      detachment. RESULTS: The result showed that the average time for the absorption
      of subretinal fluid was 14.5 days in the traditional Chinese medicine treatment
      group, 21.7 days in the control group and the visual acuity was better in the
      former than in the latter. CONCLUSIONS: The traditional Chinese medicine
      treatment could increase the absorption of subretinal fluid, the mechanisms of
      which may be that Chinese medicines regulated and improved the general blood
      circulation and local eye blood circulation and the function of blood-retinal
      barrier so that they increase the outward osmotic suction forces of the pigment
      epithelium.

PMID- 8575606
TI  - Preservation and observation of anterior ciliary vessels in rectus muscles during
      strabismus surgery.
AB  - PURPOSE: To observe the form and number of the anterior ciliary vessels (ACV) in
      rectus muscles. To train technician in preservation and observation of ACV, so
      preservation can be done in cases with a risk of anterior segment ischemia (ASI).
      METHODS: Curved foreign knife, iris hook, plastic rubber band and standard
      operating loupes (3x.) or microscope were used in the surgery on 34 cases of
      comitant strabismus and 18 cases of paralytic strabismus. RESULTS: The ACVs per
      muscle in medial, lateral, superior, inferior rectus were 3.08, 3.26, 3.50 and
      3.50 respectively in 89 muscles of 52 surgical strabismus cases. All ACVs in 16
      rectus muscles and 90 out of 220 ACVs in 73 rectus muscles were too small or too
      short to be dissected. The success rate of ACV preservation was 91.5% (119/130).
      105 out of 130 vessels were saved using loupe magnification and 14 pit pf 130
      vessels were saved under operating microscope. CONCLUSIONS: The number of ACV in
      rectus muscles are more than 2 in our observation cases. The ACV preservation has
      the clinical value of allowing us to perform muscle surgery on three or more
      rectus muscles simultaneously and get final surgical results more earlier after
      ACV in each muscle are dissected and preserved otherwise staged surgery are
      needed. The each strabismus surgeon must know this technique.

PMID- 8575608
TI  - Epidemiological survey of primary angle-closure glaucoma in Doumen.
AB  - PURPOSE: To determine the prevalence of primary angle-closure glaucoma (PACG) in
      Doumen Countty, Guangdong province. METHODS: Four villages from eight districts
      in doumen were selected by stratified, cluster and random sampling. Of a total of
      1055 people aged 45 years or over, 932 (88.62%) were examined. The examination
      and diagnostic criterion were similar to those of shunyi survey. RESULTS: The
      prevalence of PACG in subjects over 45 year of eye is 0.64%, in those over 50
      years of age is 0.85% in Doumen, which is significantly lower than the
      corresponding figure of 1.99% in shunyi (P < 0.05). CONCLUSION: This study
      identifies the prevalence of PACG in Doumen is lower than in Shunyi.

PMID- 8575607
TI  - The analysis of disparity evoked potentials by a new form of static random-dot
      stereograms.
AB  - PURPOSE: A new form of static random-dot stereograms free of monocular clues was
      designed as stimulus to elicit disparity evoked potentials. METHODS: Disparity
      evoked potentials were recorded in 40 stereo-normal subjects. The stimulator was
      a white-black static random-dot stereograms generated by a computer and had no
      monocular clues. Every subject was tested in disparity stimulus, zero disparity
      stimulus, monocular stimulus and wearing prism condition. RESULTS: A
      characteristic wide positive wave at about 250 ms was consistently recorded in
      disparity stimulus, which may be regarded as evidence of the presence of
      stereopsis. In contrast, recordings for zero disparity stimulus, monocular
      vision, stimulus and wearing prism condition all demonstrated a markedly
      difference from recording for disparity stimulus.

PMID- 8575609
TI  - Clinical analysis of steroid glaucoma.
AB  - PURPOSE: The authors accumulated 15 cases (26 eyes) of steroid glaucoma due to
      topical administration of dexamethasone or prednisolone. METHODS: From 1970 to
      1990, 26 eyes in 15 cases were observed (bilateral 11 cases, unilateral 4 cases)
      including 12 right eyes and 14 left eyes. 10 cases were male and 5 cases female
      with age ranging from 14 to 52 years averaging 28 years. 25 eyes had the
      manifestation of chronic open angle glaucoma in the clinical course, and 1 eye
      simulated an acute glaucoma attack. RESULTS: All patients had taken antiglaucoma
      medication before coming to our hospital, but the IOP was over 6.7 kPa in 9 eyes.
      The C/D ratio was equal to or over 0.6 in 9 cases (16 eyes), and the values were
      inconsistent between both eyes in 55% of the patients. Treatment for glaucoma was
      immediate discontinuation of the steroids with antiglaucoma medication if
      necessary. Three eyes received filtering operations and 2 eyes had the removal of
      subconjunctival residual steroid. Normal IOP was restored in months up to a year.
      CONCLUSION: Dexamethasone or prednisolone were the easiest to induce steroid
      glaucoma when the patients had long-term use of steroid eyedrops.

PMID- 8575610
TI  - The modality of huoxue-huayu in treatment of retinal vein occlusion.
AB  - BACKGROUND: There were some reports in China about Huoxue-Huayu therapy on
      retinal vein occlusion (RVO), but prospective and systematic studies are very
      few. The curative effect and mechanism of this therapy on RVO have not been
      reported previously. METHODS: 80 patients with RVO were randomly divided into 2
      groups, Fundus III (group A) and urokinase group (group B). Group A was treated
      by Fundus III oral liquid (a composite herbal recipe for Huoxue-Huayu or
      invigoration of blood circulation and reduction of blood stasis) 10ml/time P.O.
      t.i.d. The treatment course was 1 mouth. Group B was treated by urokinase. The
      urokinase that produced in China was used 10,000 u + 5% glucose 500ml/day i.v.
      drip for 5 days in a course, the rest 5 days going on another course. The total
      treatment courses lasted 1 month, too. RESULTS: The visual acuity in group A was
      remarkably improved while that in group B did not change. The extravasated
      retinal blood was evidently absorbed in 92.7% of the cases in group A and in
      66.7% of those in group B. The difference was significant. Fundus III also
      improved the retinal circulation, decreased the whole blood viscosity and
      fibrinogen and reduced leakage of the retinal capillaries. The total effective
      rates were 83.7% in group A and 53.7% in group B with significant statistical
      difference between the 2 groups (P < 0.01). CONCLUSION: Fundus III may alleviate
      retinal edema and necroses, improve the recovering of visual acuity, the retinal
      microcirculation, the rate of absorbing of retinal haemorrhage and treat RVO, and
      the curative effect is better than urokinase.

PMID- 8575611
TI  - Tear malate dehydrogenase, lactate dehydrogenase and their isoenzymes in normal
      Chinese subjects and patients of ocular surface disorders.
AB  - PURPOSE: To determine levels of malate dehydrogenase (MDH), lactate dehydrogenase
      (LDH) and their isoenzymes in tears of normal Chinese subjects and patients with
      ocular surface disorders. METHODS: The age range of normal subjects was 10-88,
      with 136 male and 128 female subjects. 123 patients suffered from ocular surface
      disorders. Tears were collected from lower fornix on Xinghua filter disc (0.1mm
      thick, 5mm in diameter). The values of tear MDH and LDH were determined by
      MONARCH-2000 Analyzer (U. S. A.). Their isoenzymes were separated by acetate
      cellulose electrophoresis and were determined by Model CDS-200 light
      densitometer. RESULTS: The normal values of tear LDH and MDH were 45.51 + 23.00
      81.35 + 37.84 umol.s-1/L and 11.00 + 5.33-19.50 + 9.17 umol.s-1/L respectively,
      disregarding sex or eye distriction (P > 0.05). The values of tear LDH and MDH in
      the group aged 10-19 were significantly lower than in another groups (P < 0.05).
      95% normal ranges of tear MDH aged below 19 and above 20 were 3.63-19.90 umol.s
      1/L and 4.20-36.64 umol s-1/L. 95% normal ranges of tear LDH aged below 19 and
      above 20 were 17.69-82.93 umol.s-1/L and 21.47-150.41 umol.s-1/L. The MDH
      isoenzymes comprised MDHs and MDHm, the former accounting for 80.0-89.1%. The LDH
      isoenzymes comprised 5 varieties, of which the ratio H/M of subunit H to subunit
      M was 0.196 + 0.02. Levels of tear LDH,MDH and their isoenzymes in different
      diseases were various. CONCLUSIONS: Tear LDH/MDH ratio reflected sensitively the
      metabolism of corneae and conjunctival epithelium. The changes in LDH isoenzymes
      were helpful to the differential diagnosis of external eye diseases, and the
      increase of MDHm reflected sensitively the degree of injury to the corneal
      epithelium.

PMID- 8575612
TI  - A model for the formation of ring mitochondria in retinal pigment epithelium.
AB  - PURPOSE: To investigate the mechanism and sequence of formation of ring-shaped
      mitochondria in retinal pigment epithelial cells of a chick model of gyrate
      atrophy. METHODS: Electron microscopic analysis of the ultrastructure of retinal
      pigment epithelial (RPE) mitochondria was carried out in chicks injected
      intravitreally with formoguanamine regularly (every 4 days) over the first 2
      weeks or 4 weeks post-hatching. Formoguanamine is a triazine drug which induces
      hyperornithinemic symptoms in the chick eye similar to those seen in human gyrate
      atrophy. RESULTS: A large population of irregularly shaped mitochondria was
      observed in the RPE of both peripheral and central retina. They showed extensive
      morphological changes. At 2 wk, the mitochondria appeared enlarged and abnormal
      in shape with vacuolisation, partial loss of their double membrane and reduced
      mitochondrial cristae. By 4 wk, the mitochondria had assumed a rounder, almost
      circular profile, many with central holes, so-called ring mitochondria.
      CONCLUSION: The appearance of ring-shaped mitochondria has been previously
      ascribed to the section of cupshaped three-dimensional structures. We present
      evidence that ring-shaped mitochondrial profiles arise through at least two
      different mechanisms of membrane breakdown and intraorganelle vacuolisation. The
      nature of the three dimensional structures of these abnormal mitochondria is re
      examined.

PMID- 8575613
TI  - Ontogeny of basal and regulated proopiomelanocortin-derived peptide secretion
      from fetal and neonatal pituitary intermediate lobe cells: melanotrophs exhibit
      transient glucocorticoid responses during development.
AB  - Proopiomelanocortin (POMC)-producing cells comprise nearly 100% of the adult rat
      intermediate lobe (IL) hormone-producing cells. Secretion by these cells in the
      adult is primarily under negative regulation by dopamine. Although the POMC
      derived peptide alpha-MSH has been detected in plasma of fetal rats, the
      secretory capability of fetal melanotrophs has not yet been examined directly.
      Here we have used the reverse hemolytic plaque assay to assess, at the single
      cell level, basal and regulated release by melanotrophs from fetal and early
      postnatal ages. Basal secretion was detected at the earliest age examined
      [Embryonic Day 17.5 (e17.5)], but CRH (10(-8) M) stimulated secretion was not
      observed until e19.5. As development proceeded, CRH increased both individual
      plaque sizes and the percentage of melanotrophs stimulated to secrete. An
      unexpected, transient inhibition of CRH stimulated release from melanotrophs by
      dexamethasone (DEX, 10(-6) M) was observed from e19.5-p2 (postnatal Day 2). By
      p3, however, DEX no longer inhibited melanotroph secretion while inhibition of
      CRH-stimulated release from p3 corticotrophs was readily detected. The dopamine
      agonist ergocryptine (ERG, 10(-6) M) inhibited basal secretion from melanotrophs,
      but not corticotrophs, at all ages examined. Taken together, these results
      indicate that melanotrophs undergo a maturation process in which they are
      initially nonresponsive to CRH, next possess functional CRH and steroid
      receptors, and finally, undergo functional uncoupling of steroid receptors which
      characterizes the adult IL. The loss of steroid-mediated inhibition of stimulated
      secretion parallels the arrival of catecholaminergic input into the IL. In
      contrast, the early response of melanotrophs to dopaminergic agonists, which can
      be detected 1 week prior to arrival of catecholaminergic fibers into the
      neurointermediate lobe, appears to be an intrinsic feature of these cells that is
      never present in corticotrophs.

PMID- 8575614
TI  - Expression of the ubiquitin-conjugating DNA repair enzymes HHR6A and B suggests a
      role in spermatogenesis and chromatin modification.
AB  - RAD6, a member of the expanding family of ubiquitin-conjugating (E2) enzymes,
      functions in the so-called "N-rule" protein breakdown pathway of Saccharomyces
      cerevisiae. In vitro, the protein can attach one or multiple ubiquitin (Ub)
      moieties to histones H2A and B and trigger their E3-dependent degradation. Rad6
      mutants display a remarkably pleiotropic phenotype, implicating the protein in
      DNA damage-induced mutagenesis, postreplication repair, repression of
      retrotransposition, and sporulation. RAD6 transcription is strongly induced upon
      UV exposure and in meiosis, suggesting that it is part of a damage-induced
      response pathway and that it is involved in meiotic recombination. It is
      postulated that the protein exerts its functions by modulating chromatin
      structure. Previously, we have cloned two human homologs of this gene (designated
      HHR6A and HHR6B) and demonstrated that they partially complement the yeast
      defect. Here we present a detailed characterisation of their expression at the
      transcript and protein levels. Both HHR6 proteins, resolved by 2-dimensional
      immunoblot analysis, are expressed in all mammalian tissues and cell types
      examined, indicating that both genes are functional and constitutively expressed.
      Although the proteins are highly conserved, the UV induction present in yeast is
      not preserved, pointing to important differences in damage response between yeast
      and mammals. Absence of alterations in HHR6 transcripts or protein upon heat
      shock and during the cell cycle suggests that the proteins are not involved in
      stress response or cell cycle regulation. Elevated levels of HHR6 transcripts and
      proteins were found in testis. Enhanced HHR6 expression did not coincide with
      meiotic recombination but with the replacement of histones by transition
      proteins. Immunohistochemistry demonstrated that the HHR6 proteins are located in
      the nucleus, consistent with a functional link with chromatin. Electron
      microscopy combined with immunogold labeling revealed a preferential localisation
      of HHR6 in euchromatin areas, suggesting that the protein is associated with
      transcriptionally active regions. Our findings support the idea that both HHR6
      genes have overlapping, constitutive functions related to chromatin conformation
      and that they have a specific role in spermatogenesis, involving Ub-mediated
      histone degradation.

PMID- 8575615
TI  - First blood vessels in the avian neural tube are formed by a combination of
      dorsal angioblast immigration and ventral sprouting of endothelial cells.
AB  - We studied the early pattern of neural tube (NT) vascularization in quail embryos
      and chick-quail chimeras. Angioblasts appeared first in the dorsal third at
      Hamburger and Hamilton (HH) stage 19 as single, migrating cells. Their
      distribution did not correspond to a segmental pattern. After this initial dorsal
      immigration, endothelial sprouts invaded the NT on either side of the floor plate
      (HH stage 21). These cells remained continuous with their arterial vascular
      sources, connected to the venous perineural vascular plexus at HH-stage 22, and
      formed the first perfused vessels of the NT at HH-stage 23. The same pattern of
      angiotrophic vascularization was observed in a craniocaudal sequence starting
      caudal to the rhombencephalic NT. Extremely long filopodia were observed on
      sprouting cells, extending toward the central canal and the mantle layer. The
      exclusively extraneuroectodermal origin of angioblastic cells was demonstrated
      with chick-quail chimeras. Following replacement of quail NT by chick NT graft,
      angioblast and sprout distribution in chimeras was the same as in controls. We
      conclude that the NT receives its first blood vessels by a combination of two
      different processes, dorsal immigration of isolated migrating angioblastic cells
      and ventral sprouting of endothelial cells, which derive from perfused vessels.
      The dorsal invasive angioblasts contribute to the developing intraneural vascular
      plexus after having traversed the neural tube. The initial distribution of blood
      vessels within the neuroepithelium corresponds to intrinsic random motility of
      angioblastic cells; a more regular pattern is seen later. The floor plate
      apparently prohibits connections between sprouts in both NT sides, whereas in the
      dorsal NT, such a separating effect on the migrating angioblasts does not exist.

PMID- 8575616
TI  - The sequence of regulatory events controlling the expression of the gamma D
      crystallin gene during fibroblast growth factor-mediated rat lens fiber cell
      differentiation.
AB  - The transcriptional activation of tissue-specific genes during terminal
      differentiation must be preceded by the priming of the chromatin and the
      appearance of the required transacting factors. We have timed these events for
      the transcriptional activation of the rat gamma D-crystallin gene, a lens fiber
      cell-specific gene that encodes a structural lens protein, during the (basic
      fibroblast growth factor (bFGF)-induced) in vitro differentiation of rat lens
      fiber cells. In vitro, in the presence of bFGF only, the endogenous gamma D mRNA
      accumulates between Day 10 and Day 15. When insulin is added as well, the
      differentiation process is accelerated and gamma D mRNA starts to accumulate at
      Day 8. Demethylation of the gamma D promoter region, as assessed by measuring the
      methylation state of the ThaI site at -16, occurs much sooner, within 1 day. By
      genomic footprinting, the first protein interaction with the promoter region was
      visible at Day 8; full occupancy of the promoter region could be detected only at
      Day 12. The genomic footprint identified four putative regulatory regions: -141/
      131, -88/-71, -55/-45, and -15/-4. Site-directed mutagenesis of the G residues at
      -55 and -46 resulted in a three- to fivefold decrease in promoter activity of
      transfected gamma D/CAT reporter genes and also abolished interaction with
      nuclear extract factor(s). A G-->T mutation at -43 had no effect. The -55/-45
      footprint thus derives from a proximal activator. The -88/-71 footprint
      identifies a silencer of the gamma D promoter in late fiber cell differentiation,
      as a tetramer of the -85/-67 sequence silenced a tk/CAT construct when
      transfected into fiber cells at a late stage, but not at an early stage, of in
      vitro differentiation. To time the appearance of regulatory factors, the activity
      of a -73/+45 gamma D/CAT (containing the activator region) and of a -1100/+45
      gamma D/CAT construct was measured during fiber cell differentiation. The -73/+45
      construct was active between Day 5 and Day 14, with a maximum at Day 12. The
      additional sequence information present in the -1100/+45 construct constrained
      gamma D promoter activity to between Day 8 and Day 13, with a maximum at Day 10.
      We conclude that the phased appearance of transacting factors during lens fiber
      cell differentiation controls the timing of first the activation and then the
      shutdown of the gamma D-crystallin gene promoter.

PMID- 8575617
TI  - Dispersion patterns of clonally related cells during development of the
      hypothalamus.
AB  - To identify patterns of cell generation and migration during early development of
      the hypothalamus, clones were marked with a library of retroviral vectors. The
      majority of clones analyzed at Embryonic Days 8-10 were simple radial columns. A
      small number of clones had one of three unusual patterns of dispersion. One
      unusual clone type was bilaterally symmetric across the ventral forebrain.
      Another was composed of four or more columns of cells arranged in a line along
      the ventricular surface, and a third was composed of cells that appeared to
      disperse from the typical radial columns in a plane parallel to the ventricular
      surface. The appearance of the rare clones suggests that there are different
      mechanisms of clonal dispersion during early development of the ventral forebrain
      that could play a role in patterning the hypothalamus.

PMID- 8575618
TI  - Overexpression of an Agouti cDNA in the skin of transgenic mice recapitulates
      dominant coat color phenotypes of spontaneous mutants.
AB  - The classical mouse fancy Agouti gene is responsible for the wild-type coat color
      where hairs are banded black and yellow. The Agouti gene encodes a 131-amino-acid
      secreted protein product that regulates phaeomelanin synthesis by melanocytes in
      mice. Mice with a dominant mutation at this locus, Ay, develop a yellow coat
      color, obesity, and diabetes, as the result of a deletion that results in ectopic
      overexpression of the Agouti gene mRNA in all tissues examined. Obesity and
      diabetes in Ay mutant mice could be caused by circulation of the protein, or
      localized action in specific tissues as a paracrine factor acting in cell-cell
      communication. To test these two possibilities, the Agouti cDNA was overexpressed
      in the skin of transgenic mice using either the Tyrosinase-Related Protein-1 or
      the keratin-14 (K14) promoter, the latter with and without an intron. The K14
      promoter directed high constitutive levels of expression of Agouti mRNA in the
      skin, and several lines of transgenic mice exhibited coat colors resembling
      dominant Agouti allele phenotypes. Two highly expressing K14-Agouti transgenic
      lines, with light-yellow pelage, were analyzed for obesity and hyperglycemia. The
      transgenic mice were not significantly different from the controls (P > 0.05),
      indicating that the Agouti product does not act as an endocrine factor. RNase
      protection assays revealed a correlation between the levels of dorsal and ventral
      skin expression with pigmentation/phaeomelanin phenotypes. Co-injection
      experiments with the Agouti transgenes and other transgenes demonstrated co
      integration of the two constructs at the same chromosomal site in approximately
      95% of F1 progeny, allowing transgene inheritance to be visibly detected.

PMID- 8575619
TI  - Effects of the transcription inhibitor actinomycin D on postzygotic development
      of Tetrahymena thermophila conjugants.
AB  - During Tetrahymena thermophila conjugation, new somatic macronuclei develop from
      a common zygotic nucleus derived from meiotic products of the germline, and the
      old parental somatic nucleus is destroyed. The transcription inhibitor
      actinomycin D disrupts many events of postzygotic conjugation (cycloheximide
      causes indistinguishable effects). Early treatment causes a block of all
      postzygotic development, suggesting a transcription requirement for conjugants to
      pass a checkpoint, allowing entry into postzygotic development. Thereafter, pair
      separation, resorption of the old macronucleus, and elimination of one of the new
      micronuclei are blocked if actinomycin D is added at least 1.5 hr before each of
      these events normally occurs. Treatment just before DNA rearrangements in the
      developing macronuclei (anlagen) causes aberrant anlage DNA loss, suggesting that
      this DNA loss may be caused by inhibition of gene expression involved in genome
      rearrangements. DNA loss, and correlated lethality, appear to require previous
      gene expression, since actinomycin D added earlier causes cells to arrest in
      development without anlage DNA loss, and these conjugants can (at some frequency)
      complete conjugation and make viable progeny once actinomycin D is removed. The
      old macronucleus already had been inactivated before most actinomycin D
      treatments were initiated, indicating that the various induced defects we
      observed are the result of inhibition of postzygotic gene expression, presumably
      in anlagen. The defects induced by actinomycin D are similar to defects
      previously observed in conjugants harboring nullisomic germline deficiencies but
      proficient old macronuclei.

PMID- 8575620
TI  - The distribution of collapsin-1 mRNA in the developing chick nervous system.
AB  - Collapsin-1 is a secreted glycoprotein that inhibits the extension of specific
      growth cones in vitro. It has been hypothesized to serve as a repulsive guidance
      cue for extending growth cones in vivo. Here we report the distribution of
      collapsin-1 message as demonstrated by in situ hybridization using digoxigenin
      labeled RNA probes in wholemounts and tissue sections. In the early chick brain
      collapsin-1 is expressed in specific regions of the retina, the olfactory bulb,
      and the diencephalon. In the hindbrain collapsin-1 is first expressed in
      rhombomere 5 and later in bilaterally symmetric rostrocaudal stripes. Collapsin-1
      is expressed in high levels in the ventral horn of the spinal cord and in
      ventricular stripes that extend rostrally to the hindbrain. In the periphery,
      collapsin-1 is expressed in the dermamyotome and in ectoderm and epidermis. Based
      on collapsin's expression patterns we tested axons extending from explants of
      ventral spinal cord and olfactory bulb for sensitivity to collapsin and show that
      the former are sensitive to collapsin whereas the latter are not. The
      distribution of collapsin mRNA is consistent with it playing a role in the
      organization of sensory axonal projections within the spinal cord and skin.

PMID- 8575621
TI  - Developmental roles for chromatin and chromosomal structure.
AB  - Chromosomal architecture is emerging as a key controlling influence in the
      developmental regulation of gene expression. Recent genetic experiments using
      Caenorhabditis elegans, Drosophila melanogaster, and the mouse have provided
      clear evidence for the functional differentiation of chromosomal structures
      during development. Chromosomes are visualized as highly specialized entities,
      within which the activity of particular domains is largely determined by defined
      structural proteins. At a more local level, the mechanisms regulating gene
      transcription during early embryogenesis in Xenopus and the mouse have been found
      to be dependent on the biochemical composition of individual nucleosomes. Thus,
      variation in the type and modification of chromosomal and chromatin structural
      proteins provides a dominant means of controlling the transcriptional activity of
      individual genes, individual chromosomal domains, and of entire chromosomes.

PMID- 8575622
TI  - Developmental and tissue-specific regulation of the murine cardiac actin gene in
      vivo depends on distinct skeletal and cardiac muscle-specific enhancer elements
      in addition to the proximal promoter.
AB  - Cardiac actin is an early marker of cardiac and skeletal muscle lineages in the
      mouse. After birth, the gene is down-regulated in skeletal muscle. High-level
      expression of the murine cardiac actin gene in skeletal myotubes in vitro
      involves distal (-7.8/-7.0 kb) and proximal (-5.4/-3.5 kb) enhancer sequences as
      well as the proximal promoter (-0.7/+0.1 kb). Transgenic mice carrying an nlacZ
      reporter gene under the control of different fragments of the upstream region of
      the cardiac actin gene were generated. This analysis led to the conclusions that
      (1) the proximal promoter is a weak but tissue specific element in vivo, (2)
      consistent high-level expression in skeletal muscle depends on the presence of at
      least one of the enhancers, (3) expression in adult cardiac muscle requires a
      cardiac enhancer located in the (-5.4/-0.7 kb) region, and (4) a construct
      containing these three elements gives a strong specific expression of the
      transgene in the heart throughout the life of the animal and in embryonic
      skeletal muscle. All transgenes tested reproduce the down-regulation observed in
      adult skeletal muscle for the cardiac actin gene. Nonuniform expression of these
      transgenes in the heart may mark cardiomyocytes derived from different cardiac
      progenitors.

PMID- 8575623
TI  - Proneural and neurogenic genes control specification and Morphogenesis of
      stomatogastric nerve cell precursors in Drosophila.
AB  - The stomatogastric nervous system (SNS) of the Drosophila embryo develops from a
      placode which appears in the stomodeam epithelium. Most cells of this placode
      invaginate as three pouches (the iSNSPs) into the interior of the embryo. After
      separating from the stomodeum, the SNS pouches transiently form epithelial
      vesicles and eventually dissociate into solid clusters of cells which migrate on
      the foregut epithelium and differentiate into the neurons of the SNS. Prior and
      during iSNSP invagination, two small subpopulations of SNSPs (dSNSPs and tSNSPs)
      delaminate as individual cells from the SNS placode (Hartenstein et al., 1994).
      The results presented in this paper show that the neurogenic and proneural genes
      are expressed and required during all phases of SNS development to control the
      number, pattern, and structural characteristics of the SNSP subpopulations.
      First, loss-of-function mutations of the proneural and gain-of-function mutations
      of the neurogenic genes result in the absence or reduction of delaminating SNSPs;
      loss of function of neurogenic genes leads to the overproduction of d/tSNSPs and
      a loss of iSNSPs. Second, both proneural and neurogenic genes are involved in the
      invagination and dissociation of iSNSPs. Reduction of neurogenic gene function
      leads to a premature dissociation of iSNSPs; gain of neurogenic gene function
      blocks invagination and dissociation of these cells. Since all iSNSPs form a
      homogenous population with regard to their differentiative fate as SNS neurons,
      these results indicate that lateral inhibition is not a necessary aspect of the
      developmental process controlled by neurogenic and proneural gene function.

PMID- 8575624
TI  - Cell autonomous expression of perlecan and plasticity of cell shape in embryonic
      muscle of Caenorhabditis elegans.
AB  - Perlecan, a component of the extracellular matrix (ECM), is essential for
      myofilament formation and muscle attachment in Caenorhabditis elegans. We show
      here that perlecan is a product of muscle and that it behaves in a cell
      autonomous fashion. That is, perlecan expressed in an individual muscle cell does
      not spread beyond the borders of the ECM underlying that cell. Using a polyclonal
      antibody that recognizes all isoforms of perlecan, we demonstrate that this
      protein first appears extracellularly at the comma stage (approx. 350 min) of
      development. We also show that during morphogenesis muscle cells have a
      heretofore undescribed plasticity of shape. This ability to regulate cell shape
      allows cells within a muscle quadrant to compensate for missing cells and to form
      a functional quadrant. A dramatic example of this morphological flexibility can
      be observed in animals in which the D blastomere has been removed by laser
      ablation. Such animals, lacking 20 of the 81 embryonic body wall muscle cells,
      can survive to become viable adult animals indistinguishable from wildtype
      animals. This demonstrates that the assembly of an embryo via a stereotypic
      lineage does not preclude a more general regulation during morphogenesis. It
      appears that embryos are flexible enough to immediately compensate for drastic
      alterations in tissue composition, a feature of development that may be of
      general importance during evolution.

PMID- 8575625
TI  - orthodenticle is required for photoreceptor cell development in the Drosophila
      eye.
AB  - Drosophila photoreceptor cells (R cells) develop from the eye imaginal during the
      third instar larval stage and acquire their adult morphology during pupation. We
      show that orthodenticle (otd), a homeobox gene, is required for R-cell
      morphogenesis during pupation. otdUV-insensitive (otduvi) is a hypomorphic allele
      of otd that only affects R-cell development. The R-cell rhabdomeres are
      disorganized in otduvi, and there is a disruption of proximal-distal development
      in the eye. The otd genomic structure was determined and resulted in the
      identification of a deletion in the third intron of otduvi. Sequences
      encompassing this deletion are able to direct expression of the lacZ reporter
      gene at all stages of the developing visual system, including the photosensitive
      cells of Bolwig's organ, the ocelli, and the adult eye. The third intron enhancer
      is the primary regulatory element controlling otd in the R cells and is not under
      the control of the glass gene.

PMID- 8575626
TI  - Hensen's node from vitamin A-deficient quail embryo induces chick limb bud
      duplication and retains its normal asymmetric expression of Sonic hedgehog (Shh).
AB  - Both Hensen's node, the organizer center in chick embryo, and exogenous retinoic
      acid are known to induce limb duplication when grafted or applied to the host
      chick limb bud. Retinoic acid is known to be present in the node and has been
      proposed as the putative morphogen for chick limb development. Here, we report
      that Hensen's node from vitamin A-deficient quail embryo induces limb duplication
      in the host chick embryo similar to that induced by the node from vitamin A
      sufficient control embryos. We also demonstrate that the expression of Sonic
      hedgehog (Shh), recently shown to be the mediator of polarizing activity in the
      chick limb bud, is not affected by the endogenous vitamin A status of the embryo.
      Furthermore, whole-mount in situ hybridization revealed asymmetry of Shh
      expression in the Hensen's node of both vitamin A-sufficient and -deficient quail
      embryos. Retinoids were not detectable in the eggs from which vitamin A-deficient
      embryos were obtained. Extracts from normal embryos induced a level of expression
      of reporter gene equivalent to the presence of 3.4 pg of active retinoids per
      embryo, while those from vitamin A-deficient embryos induced a baseline level of
      reporter gene expression similar to that of the controls. Our studies suggest
      that endogenous retinoic acid is not involved in Shh expression nor in regulating
      its asymmetry during normal early avian embryogenesis and support the current
      view that endogenous retinoic acid may not be a direct morphogen for limb bud
      duplication.

PMID- 8575627
TI  - Progressive spatial restriction of Sek-1 and Krox-20 gene expression during
      hindbrain segmentation.
AB  - After segmentation of the vertebrate hindbrain, expression of the zinc-finger
      gene Krox-20 and the receptor tyrosine kinase gene Sek-1 is precisely restricted
      to rhombomeres (r) 3 and 5. This precise segmental expression is likely to
      reflect a critical requirement for these rhombomeres to acquire a distinct and
      homogeneous identity and raises the question as to how this relates to the
      intermingling and restriction of cell movement during segmentation. We have
      analysed Krox-20 and Sek-1 expression in the mouse and chick hindbrain at single
      cell resolution using whole-mount in situ hybridisation and immunocytochemistry.
      We find that, in the mouse, the presumptive r3 and r5 expression domains each
      arise as narrow stripes that then broaden, suggestive of a recruitment of cells
      to an r3/r5 identity and/or a segmental regulation of cell proliferation. In
      addition, we find that expression of these genes initially occurs in fuzzy
      domains, and that these are progressively restricted to segmental domains,
      although occasional "violating" cells are observed even after segmentation. We
      propose that the establishment and maintenance of these segmental domains may
      involve both a dynamic regulation of r3/r5 identity and the restriction of cell
      movement across rhombomere boundaries.

PMID- 8575628
TI  - Formation and maturation of the calcium release apparatus in developing and adult
      avian myocardium.
AB  - Muscle fibers release large amounts of calcium from an internal compartment, the
      sarcoplasmic reticulum (SR), during activation. Two proteins are involved in this
      process and its control: plasma membrane calcium channels, or dihydropyridine
      receptors (DHPRs), and SR calcium release channels, or ryanodine receptors
      (RyRs). The two proteins form part of a structural complex, perhaps unique to
      muscle cells, which allows an interaction between plasma membrane and SR,
      resulting in calcium release from the latter. The surface-SR interaction is a
      step in the coupling between electrical events in the plasma membrane and
      contraction (excitation-contraction coupling). The structural complexes have been
      called calcium release units. One key to further understanding the control of
      calcium homeostasis in muscle is knowledge of how DHPRs and RyRs assemble into
      calcium release units. We have studied the development of avian myocardium, using
      immunocytochemistry to locate DHPRs and RyRs and electron microscopy to follow
      the formation of calcium release units containing feet (RyRs) and large membrane
      particles (presumably DHPRs). We find that the initial step is a docking of SR
      vesicles to the plasma membrane, followed by the appearance of feet in the
      junctional gap between SR and plasma membrane. Feet aggregate in ordered arrays,
      and the arrays increase in size until they fill the entire junctional gap.
      Clustering of membrane particles, presumably DHPRs, is apparently coupled to
      clustering of feet, since the two junction components assemble within patches of
      membrane of approximately equal size and containing an approximately constant
      ratio of particles to feet. Thus, despite the fact that no evidence exists for a
      direct interaction between DHPRs and RyRs in cardiac muscle, some mechanism
      exists to ensure that the two molecules are clustered in proximity to each other
      and in the appropriate proportion.

PMID- 8575629
TI  - Skeletal myogenesis: the preferred pathway of chick embryo epiblast cells in
      vitro.
AB  - The epiblast layer of the chick embryo gives rise to all embryonic tissues. In
      vitro analyses were carried out to determine whether epiblast cells could form
      skeletal muscle prior to entry into the primitive streak. Epiblasts were
      separated from the mesoderm, hypoblast, and primitive streak, dissociated to
      produce a single cell suspension, and plated at high density. Myogenesis began on
      the first day in culture, and by the fifth day most cells had differentiated into
      skeletal muscle. Some cells differentiated without replicating. MyoD messenger
      RNA was present in epiblast tissue and translated in practically all cells in
      culture. Cells from regions of the epiblast which do not form muscle later in the
      embryo did so in vitro. Epiblasts cultured for 2 days as an intact epithelium, or
      in the presence of the mesoderm and hypoblast, did not undergo myogenesis. These
      findings demonstrate that myogenic potential is wide-spread within the primitive
      streak stage epiblast, and that muscle differentiation, which occurs relatively
      autonomously in culture, can be prevented by cell and tissue interactions.

PMID- 8575630
TI  - Unmasking mRNA in clam oocytes: role of phosphorylation of a 3' UTR masking
      element-binding protein at fertilization.
AB  - During meiotic maturation or after fertilization of invertebrate and vertebrate
      oocytes, many of the quiescent stored mRNAs are recruited into polysomes. In the
      clam, Spisula solidissima, such masked messages include the abundant mRNAs
      encoding cyclin A and the small subunit of ribonucleotide reductase. We have
      previously shown that mRNA-specific unmasking of these two messages can be
      achieved in vitro, in oocyte cell-free extracts, by the addition of antisense
      RNAs corresponding to a fairly short (130-140 nucleotides) segment in their
      cognate 3' untranslated regions. We postulated that the antisense RNAs prevented
      the binding of a masking repressor protein (Standart et al., 1990). Here we
      report UV-crosslinking and gel retardation studies which show that the masking
      portions of the translationally regulated mRNAs bind an oocyte protein of 82 kDa
      (p82), which is phosphorylated after fertilization. This modification was
      accompanied by altered RNP complex formation in gel retardation assays. These
      changes presumably reflect the activation of translation of the masked mRNAs. The
      role of p82 phosphorylation in maternal mRNA unmasking was assessed in a novel in
      vitro activation system developed from clam oocytes, based upon the natural rise
      in pH which accompanies fertilization. Concomitant with mRNA unmasking, several
      kinases, including cdc2 and MAP kinases were activated in this system, as was p82
      phosphorylation. Inhibitors of serine/threonine kinases, including 6-DMAP,
      staurosporine, and H7 inhibited p82 phosphorylation, whereas inhibitors of
      tyrosine kinases, protein kinase C, cAMP-dependent protein kinase, and p70s6k did
      not prevent this modification. A specific inhibitor of cdc2 kinase, p27Kip1,
      prevented p82 phosphorylation and translational activation, strongly suggesting
      that p82 modification is required for unmasking.

PMID- 8575631
TI  - Expression of the actin gene family in embryos of the sea urchin Lytechinus
      pictus.
AB  - The genome of the sea urchin Lytechinus pictus includes genes encoding four
      cytoskeletal actins LpC1-4 and the muscle actin LpM. Gene-specific probes
      corresponding to 3' noncoding termini have been used to characterize their
      patterns of expression by in situ hybridization. The gene encoding LpC1 actin,
      which is most similar in sequence to the Strongylocentrotus purpuratus CyI actin,
      has a complex developmental profile of expression. LpC1 transcripts become
      prominent in the archenteron and secondary mesenchyme cells of embryos, as well
      as in adult testis and ovary. The LpC2 actin gene is predominantly expressed in
      aboral ectoderm of embryos, similarly to the pattern of expression of its closest
      relatives in S. purpuratus, the SpCyIIIa and SpCyIIIb actin genes. The LpC3 actin
      gene is expressed at low levels in secondary mesenchyme cells. The LpC4 actin
      gene is expressed in a subset of primary mesenchyme cells which may be actively
      engaged in skeletogenesis. Transcripts of the LpM gene accumulate in esophageal
      muscle cells beginning during gastrulation before overt differentiation. Each of
      the L. pictus actin genes has a distinct pattern of expression, none of which is
      identical to that of any S. purpuratus actin gene. These results indicate that
      the regulation of expression of members of the actin gene family, even those
      likely to have common ancestors, has diverged as these sea urchin species
      diverged.

PMID- 8575632
TI  - Digit induction by Hensen's node and notochord involves the expression of shh but
      not RAR-beta 2.
AB  - It is well established that Hensen's nodes can induce the formation of
      supernumerary digits after grafting into the anterior margin of the developing
      limb bud. The recent finding that distinct mesodermal cell populations are
      segregated within the node has made it possible to isolate different prospective
      cell types in an attempt to correlate digit-inducing ability with cell fate. We
      find that the prospective notochord cells contained within Hensen's node are able
      to induce supernumerary digits, whereas presumptive somite cells cannot. This
      early difference in inducing ability persists into later stages of development:
      epithelial somites are unable to induce while notochord from all lengths of the
      neuraxis continues to induce. Using probes to retinoic acid receptor-beta 2 and
      sonic hedgehog (shh) we find no evidence to support the idea that inducing
      tissues generate extra digits by releasing retinoic acid into adjacent limb
      tissue but find that the inducing ability of a tissue correlates with its
      expression of shh.

PMID- 8575633
TI  - Low-affinity NGF-receptor and E-N-CAM expression define two types of olfactory
      nerve ensheathing cells that share a common lineage.
AB  - Previously, we have shown that the O4 antibody can be used to define and purify
      olfactory nerve ensheathing cells (ONECs) from the rat olfactory bulb by
      fluorescence-activated cell sorting. In this study, using a larger panel of
      neural markers, we demonstrate that this apparently homogeneous population of
      ONECs possess a heterogeneous antigenic profile both in vivo and in vitro. The
      antigenic profile of the sorted cells initially correlated with their antigenic
      profile in vivo, although expression of some of the markers was either lost or
      gained during time in culture. These changes were influenced by the culture
      conditions, with a greater loss of "typical" ONEC markers in serum-containing
      medium. In serum-free medium, which maintains the cells in a phenotype that
      closely resembles their in vivo counterparts, we were able to reclassify the
      ONECs into two cell types based on morphology and antigenic phenotype by using
      antibodies to polysialic acid (correlating with the embryonic form of N-CAM
      expression) and the low-affinity nerve growth factor receptor. A detailed
      immunocytochemical study of the developing olfactory system showed that these two
      cell types could also be detected along the entire length of the olfactory nerve
      and the outer layer of the olfactory bulb from Embryonic Day 14 to adulthood,
      suggesting they were not an in vitro artefact. To address the relationship
      between the two cell types we constructed a clonal ONEC cell line by retroviral
      infection with the temperature-sensitive mutant gene of the large T antigen. This
      clonal cell line contained cells that expressed antigenic phenotypes of both
      classes of ONECs, suggesting that both cell types are related and share a common
      lineage.

PMID- 8575634
TI  - Early elements in gastropod neurogenesis.
AB  - The first elements of the nervous system of pond snails appear in the very early
      veliger stage of development at much earlier times than any previously described
      neurons. The first three cells are reactive to antibodies raised against both the
      neuropeptide FMRFamide and tubulin and their somata are located posteriorly
      within the embryo, not in anterior regions, as would be consistent with current
      concepts of gastropod neurogenesis. Furthermore, the extensive, anteriorly
      directed fibers from these cells appear to form a scaffold upon which the central
      ganglia and interconnecting pathways later develop. These findings challenge
      current thoughts on the origins of early embryonic neurons and on possible
      inductive cues and mechanisms of axonal navigation important in the development
      of the molluscan nervous system.

PMID- 8575635
TI  - Analysis of Wnt/Engrailed signaling in Xenopus embryos using biolistics.
AB  - We adapted the Biolistics Particle Delivery System for the introduction of DNA
      into Xenopus embryos, allowing us to modulate the expression of different genes
      at specific time points during development. In the present study we applied the
      Biolistics method to the study of the wnt-engrailed signaling cascade in the
      developing Xenopus embryo. We show that ectopic expression of Xwnt-1 and Xwnt-5C
      is sufficient to activate specifically XEn-1 and not XEn-2.

PMID- 8575636
TI  - Differential distribution of cAMP receptors cAR2 and cAR3 during Dictyostelium
      development.
AB  - Signal transduction via a family of cAMP receptor subtypes (cARs) is critical for
      proper development in the cellular slime mold Dictyostelium. Genes encoding four
      related subtypes have been cloned and their expression, based on RNA
      accumulation, has been previously reported. Here we report the differential
      spatial and temporal distribution of cAR2 and cAR3 proteins, based on indirect
      double immunofluorescence. Cells were transformed with a carB::lacZ construct,
      and an antibody against beta-galactosidase was used to visualize cAR2 expression.
      Simultaneously, a cAR3-specific antibody was used to identify cAR3-expressing
      cells. Results indicate that by the time of tip formation (12-14 hr) both
      receptors are expressed and distribute in a virtually nonoverlapping pattern,
      with cAR2 being expressed on anterior, prestalk cells and cAR3 present in the
      rest of the organism. Differential distribution of these two receptor subtypes
      may result in distinct cAMP signaling mechanisms in the two major regions of the
      organism.

PMID- 8575637
TI  - Left-right asymmetric localization of flectin in the extracellular matrix during
      heart looping.
AB  - The early embryo is initially bilaterally symmetrical. One of the first distinct
      indications of asymmetry in the embryo occurs during heart looping. The midline
      tubular heart begins to bend to the right to form a C-shaped structure around 30
      hr of development in the avian model. A molecular basis for heart asymmetry and
      direction of looping is not known, although factors inherent to the myocardium
      are believed to underlie looping. A left-right asymmetric localization of a
      specific molecule in the bilateral heart forming regions has not been reported
      previously. One molecule that we are calling flectin (flectere, in L., to bend or
      to loop) shows a bilateral asymmetric localization early in the heart forming
      mesoderm and continues to be expressed asymmetrically in a highly organized
      manner in the cardiac jelly during heart looping. This large extracellular matrix
      molecule has been identified using a monoclonal antibody F-22 (Mieziewska et al.,
      1994a,b). Flectin shows a discrete spatiotemporal pattern of extracellular matrix
      expression during avian heart development. An asymmetric expression of flectin is
      observed during heart development at stage 7+/8- (approximately at 24 hr of
      development around the 3-somite stage). It is predominantly expressed in the left
      precardiac mesoderm at this developmental period. Between stages 12 and 14,
      flectin continues to be asymmetrically expressed in the myocardium and is
      localized at high levels on the basal side of the myocardium and within the
      cardiac jelly extending to the endocardial cell surfaces. In the same plane of
      the looping part of the heart it is differentially organized within the cardiac
      jelly on the convex side and in the outer loop areas. A reduced expression is
      apparent anteriorly and posteriorly along the tubular heart. The initial
      asymmetry of localization is maintained throughout the tubular heart. At stage 22
      (Embryonic Day 3.5), intensity of immunolocalization of flectin is significantly
      decreased, with left-right asymmetry becoming less discernible or absent. It
      again is expressed in Day 10 embryonic hearts. Flectin expression appears to be
      modulated by retinoids. In vitamin A-deficient quail embryonic hearts that do not
      loop (Dersch and Zile, 1993; Twal et al., 1995), flectin protein expression is
      decreased and disorganized, as are other extracellular matrix components
      comprising the cardiac jelly.

PMID- 8575638
TI  - Neurons and ecdysteroids promote the proliferation of myogenic cells cultured
      from the developing adult legs of Manduca sexta.
AB  - During metamorphosis in the hawkmoth Manduca sexta, larval leg motoneurons
      survive the degeneration of their target muscles to innervate new muscles that
      form during the development of the adult legs. Observation of muscle development
      in vivo suggest that there are close interactions between motor terminals and the
      muscle precursor cells at the earliest stages of muscle formation and surgical
      denervation compromises further development of adult muscles. Here we describe a
      nerve/muscle coculture system that allows further exploration of this critical
      developmental interaction. Muscle precursor cells derived from the developing
      thoracic legs of early pupae and cultured in the presence of neurons assumed a
      spindle-like morphology and fused to form multinucleate contractile myotubes.
      Contractile fibers did not form in cultures of muscle precursor cells alone. In
      the presence of neurons the rate of bromodeoxyuridine (BrdU) incorporation into
      myonuclei was significantly enhanced, suggesting that neurons promote the
      proliferation of myogenic cells. This effect was not unique to thoracic leg
      motoneurons of the early pupal stage, in that larval thoracic neurons as well as
      neurons from the pupal brain or abdominal ganglia were also effective at
      enhancing BrdU incorporation and the formation of contractile muscle fibers.
      Medium conditioned by neurons was ineffective at promoting BrdU incorporation,
      and in cocultures BrdU incorporation was enhanced only in regions of physical
      overlap between neurons and muscle precursor cells, suggesting that a very close
      range interaction was involved. Tetrodotoxin-sensitive neuronal activity was not
      required for the effect on muscle development, but fixed neurons were
      ineffective. The insect steroid hormone 20-hydroxyecdysone enhanced BrdU
      incorporation into the nuclei of myogenic cells in both the presence and the
      absence of neurons. The results suggest that both neurons and ecdysteroids play
      an important regulatory role in adult muscle development, at least in part by
      enhancing the proliferation of myogenic cells.

PMID- 8575639
TI  - The developmentally restricted pattern of expression in the male germ line of a
      murine cyclin A, cyclin A2, suggests roles in both mitotic and meiotic cell
      cycles.
AB  - We have isolated cDNAs encoding a murine cyclin A, designated cyclinA2, and have
      examined its in vivo expression at the level of both mRNA and protein, with
      particular focus on the male germ line. Cyclin A2 is expressed in embryos and in
      a variety of adult tissues, including the testis. In the testis, however, a
      striking cellular specificity of expression was observed. At both the DNA and
      protein levels, the predominant sites of cyclin A2 expression were in the germ
      line stem cells, the spermatogonia, and in highest levels in preleptotene
      spermatocytes, cells in which premeiotic DNA synthesis occurs. The concurrent
      localization of cyclin A2 mRNA and protein further suggested that cyclin A2 is
      regulated at the level of transcription in these cells. The observed cellular
      specificity of cyclin A2 expression is consistent with its function during
      mitosis in the stem cell stage of this lineage, while the restricted meiotic
      stage localization suggests function in G1/S or S but not in the meiotic
      divisions per se.

PMID- 8575641
TI  - Ontogeny of basal and regulated secretion from POMC cells of the developing
      anterior lobe of the rat pituitary gland.
AB  - Proopiomelanocortin (POMC)-producing cells are present in both the anterior (AL)
      and intermediate (IL) lobes of the adult rat pituitary. Both cell types are
      derived from a single embryonic rudiment, Rathke's pouch, and synthesize the same
      hormone precursor, POMC, but differ in the pattern of precursor processing and
      regulation of peptide secretion. Here we have used the reverse hemolytic plaque
      assay to determine the ontogeny of basal and regulated secretion by AL POMC
      cells. Basal secretion of beta-endorphin was first observed at Embryonic Day 13.5
      (e13.5), the age when POMC-derived peptides were first detected
      immunocytochemically. Peptide secretion stimulated by corticotropin releasing
      hormone (CRH; 10(-8) M) was first detected at e15.5. The CRH-stimulated secretion
      involved two different components: (1) an increase in the amount of hormone
      secreted per cell (increase in plaque size) as well as (2) an increase in the
      number of plaque-producing cells. The greatest stimulation by CRH was observed at
      e16.5, a time when AL POMC mRNA levels increase significantly and when CRH
      neurons are first detected immunocytochemically in the hypothalamus. CRH
      stimulated secretion, but not basal release, was inhibited by preincubation with
      dexamethasone (DEX; 10(-6) M) as early as e15.5, while the dopamine agonist
      ergocryptine (ERG; 10(-6) M) did not alter basal or CRH-stimulated release at any
      age studied. These results demonstrate that AL POMC cells are capable of hormone
      secretion as early as POMC peptides are first detected immunocytochemically and
      that these cells respond in an adult-like manner to physiological regulators soon
      after their initial appearance. Moreover, these responses remain unaltered during
      the early postnatal stress-nonresponsive period, suggesting that deficits at this
      time must lie at a level other than the corticotroph. Taken together, these
      results show that AL POMC cells possess functional regulatory receptor systems
      prior to maturation of the hypothalamic-hypophyseal portal system.

PMID- 8575640
TI  - Initial organization of neurons and tracts in the embryonic mouse fore- and
      midbrain.
AB  - We investigated the potential role of rostral-caudal and dorsal-ventral
      subdivisions of the early rostral brain by relating these subdivisions to the
      early patterning of neuron cell bodies and their axon projections. The earliest
      neurons were mapped using the lipophilic axon tracers diI and diO on embryos
      fixed on embryonic days 9.5-10.5 (E9.5-E10.5); neuromeric boundaries were marked
      by diO. The tracts were small in number, were organized orthogonally (2 dorsal
      ventral and 4 rostral-caudal), and originated from groups of cell bodies which we
      term "sources." Two parallel longitudinal axon systems, one dorsal (the tract of
      the postoptic commissure and the mesencephalic tract of the trigeminal nerve) and
      one ventral (the mammillotegmental tract and the medial longitudinal fasciculus),
      projected caudally from the prosencephalon into the rhombencephalon. We argue
      that the dorsal longitudinal pathway marked the boundary between the alar and
      basal plates along the entire neuraxis. The dorsal-ventral axons coursed
      circumferentially and either crossed the midline (forming the posterior and
      ventral tegmental commissures) or turned caudally without crossing the midline.
      The dorsal-ventral axons were not generally restricted to the interneuromeric
      boundaries, as others have suggested. Earlier, all neighboring neurons projected
      their axons together; later, nearby neurons projected into different pathways.
      Some tracts originated in single neuromeres, while other tracts had origins in
      two or more neuromeres. The dorsal longitudinal axons altered course at several
      of the borders, but the ventral longitudinal axons did not. In summary, the early
      subdivisions appeared to influence some, but not all, aspects of tract formation.

PMID- 8575642
TI  - Spatial, temporal and hormonal regulation of programmed muscle cell death during
      metamorphosis of the frog Xenopus laevis.
AB  - No examination to date has been made of apoptosis during vertebrate muscle
      development. The authors recently reported programmed muscle cell death to be
      important in tail degeneration as well as in the larval-to-adult conversion of
      the dorsal body muscles of Xenopus laevis during metamorphosis [30]. In the
      present study, we examined programmed cell death (PCD) of the dorsal body and
      tail muscle morphologically and biochemically, with special attention to whether
      apoptotic processes, such as chromatin fragmentation and apoptotic body-formation
      actually occur, and whether triiodothyronine (T3) induces such processes. Light
      microscopic observation indicated muscle fibers break down into short fragments
      (sarcolytes or muscle apoptotic bodies) during the metamorphic climax, not only
      in tail but also in larval-type fibers of dorsal body muscles. Apoptotic bodies
      first appeared near the base of the tail in early climax (stage 59) when the T3
      level is quite high, and thereafter expanded in an anterior direction in the
      dorsal body and posteriorly in the tail. The ratio of apoptotic area to total
      muscle area became maximum (10%-30% in dorsal body muscles and 50% in the tail)
      at the climax (stages 63-64). During these stages, genomic DNA fragmented into
      oligonucleosome-sized units (200 bp, 400 bp, 600 bp ...) in both body and tail
      muscles. To confirm whether this chromatin fragmentation is associated with
      apoptotic bodies, in situ DNA nick end labeling (TUNEL) was applied to sections
      of the dorsal body and tail muscles. Labeled muscle nuclei could be found only in
      muscle apoptotic bodies but not in intact muscle fibers, indicating DNA
      fragmentation was associated with cell fragmentation during metamorphosis. It
      thus follows that morphological (apoptotic body formation) and biochemical
      (fragmentation of chromatin) processes occurring during PCD of dorsal body and
      tail muscles are identical. To determine whether T3 regulates programmed muscle
      cell death, the effects of T3 on DNA ladder formation were examined in tails
      cultured in vitro. The oligonucleosomal DNA ladder was found to form only in
      tails incubated with T3, thus showing T3 to induce programmed muscle cell death
      without interaction with other endocrine organs during metamorphosis.

PMID- 8575643
TI  - Regulated expression of a novel laminin beta subunit during the development of
      the chick embryo.
AB  - In order to define specific laminin variants implicated in organogenesis, we have
      undertaken a systematic search to detect and characterize novel laminin subunits,
      the expression of which is both developmentally regulated and tissue-specific.
      cDNA prepared from embryonic chick tissues was amplified by the polymerase chain
      reaction (PCR) with degenerate primers based on conserved sequences in domains V
      and VI of members of the laminin beta subunit family. Restriction mapping,
      cloning and sequencing of PCR products demonstrated a novel cDNA, the derived
      protein sequence of which displayed greatest homology with laminin beta subunits.
      However, the degree of amino acid divergence, comparison of sequence motifs and
      pattern of expression indicates that the cloned cDNA does not code for the avian
      orthologue of a previously characterized laminin beta subunit. Northern blot
      analysis showed that the expression of the 6-kb mRNA coding for the novel subunit
      was restricted to the skin. The mRNA was not detectable before day 5 of chick
      embryonic development, after which in situ hybridization showed expression only
      in surface ectoderm cells and subsequently in the epidermis. The developmentally
      regulated ectodermal expression of the novel beta subunit, prior to condensation
      of mesenchymal cells to form the dermis, is consistent with a specific role for
      this laminin isoform in the development and maintenance of the skin.

PMID- 8575644
TI  - Expression of syndecan-1 changes during the differentiation of visceral and
      parietal endoderm from murine F9 teratocarcinoma cells.
AB  - F9 teratocarcinoma stem cells treated with retinoic acid differentiate in
      suspension into embryoid bodies with an outer layer of visceral endoderm
      surrounding a core of largely undifferentiated cells. The visceral endoderm
      containing embryoid bodies, when plated onto an extracellular matrix coating,
      give rise to parietal endoderm outgrowth. These in vitro cell cultures mimic both
      geometrically and biochemically the differentiation of visceral and parietal
      endoderm in the early mouse embryo and, thus, were used as a model system for the
      study of molecular and cellular mechanisms underlying the differentiation of the
      extraembryonic endoderm lineages. We have investigated the expression of syndecan
      1, an integral membrane proteoglycan that binds to multiple components of the
      extracellular matrix and basic FGF, during visceral endoderm differentiation and
      parietal endoderm outgrowth. Syndecan-1 immunostaining is detected on all cell
      surfaces in the undifferentiated embryoid bodies and in the differentiating
      embryoid bodies prior to the formation of the visceral endoderm. Following the
      differentiation of visceral endoderm, syndecan-1 localizes predominantly to the
      basal surface of this epithelial layer, while syndecan-1 staining in the core of
      differentiated embryoid bodies is faint. Quantitation of cell associated syndecan
      1 indicates that syndecan-1 is down-regulated during embryoid body
      differentiation. However, northern analysis shows that the amounts of steady
      state syndecan-1 mRNA are the same in undifferentiated versus differentiated
      embryoid bodies, suggesting post-transcriptional regulation of syndecan-1
      expression in the differentiating embryoid body. Analysis of syndecan-1
      distribution in the outgrowth culture by immunofluorescence demonstrates that
      syndecan-1 is absent from the cell surface of parietal endoderm. However, a
      substantial amount of syndecan-1 is detected inside parietal endoderm cells.
      While all three cell types release syndecan-1 ectodomain into the culture medium,
      the parietal endoderm outgrowth releases more syndecan-1 ectodomain than the
      differentiated embryoid body. These data suggest that the post-transcriptional
      control and post-translational shedding of syndecan-1 from the cell surface are
      developmentally regulated during the differentiation of visceral to parietal
      endoderm and the migration of parietal endoderm.

PMID- 8575645
TI  - Parvalbumin expression during developmental differentiation of the rat ovary.
AB  - Parvalbumin (PV) is a high-affinity Ca(2+)-binding protein which is expressed in
      a limited number of vertebrates tissues and restricted to a few distinct cell
      types. It has been shown by biochemical methods to be present in the adult rat
      ovary, but cellular localizations or developmental appearance have not been
      described until now. This study describes the presence of PV and its transcripts,
      analyzed by immunohistochemistry and in situ hybridization, respectively, during
      the postnatal development of the rat ovary: 13 developmental stages between day 1
      and day 83 were examined. In ovaries 1-16 days old, neither PV mRNA nor PV was
      observed in any caaaaaaaaaaaaaay. By contrast, starting from day 18 postpartum,
      both PV mRNA and PV were detected in low amounts, simultaneously with the onset
      of differentiation of secondary intestitial gland cells in the ovarian
      interfollicular stroma. PV and its transcripts were primarily detected in
      conspicuous patches of interstitial gland tissue and in the differentiated thecal
      cells around the large follicles, and PV appeared to be fully expressed 33 days
      after birth. The parallel time courses of PV mRNA and PV accumulation during
      developmental differentiation, and the appearance of a steroid-producing cellular
      phenotype as well as the strict cellular colocalization of these two features,
      strongly suggest involvement of PV in the steroid metabolism of these cells, as
      earlier proposed for the Leydig cells of the testis. According to this
      hypothesis, we also show that suppression of gonadotrophic hormone production by
      hypophysectomy of adult rats totally suppresses PV production in parallel with
      the disappearance of the morphological features typical of steroid-producing
      cells in the remaining interstitial tissue of the ovary.

PMID- 8575646
TI  - Inhibitors of ADP-ribosylation suppress phenotypic modulation and proliferation
      of smooth muscle cells cultured from rat aorta.
AB  - The effects of hexamethylenebisacetamide (HMBA), an inhibitor of poly-ADP
      ribosylation, and meta-iodobenzylguanidine (MIBG), an inhibitor of mono-ADP
      ribosylation, on the phenotypic properties and proliferation of cultured rat
      aortic smooth muscle cells were studied using a combination of structural and
      chemical methods. The results show that HMBA and MIBG both slowed down the
      transition of the cells from a contractile to a synthetic phenotype in primary
      culture. While the control cells rapidly lost most of their myofilaments and
      built up an extensive endoplasmic reticulum and Golgi complex, a conspicuous
      fraction of the drug-treated cells retained a characteristic smooth muscle
      morphology for at least 6 days. Moreover, most of the treated cells remained
      positive for smooth muscle alpha-actin and desmin throughout this period. In
      contrast, the drugs lacked distinct effects on cell morphology and cytoskeletal
      organization in secondary cultures. Nevertheless, they strongly inhibited serum
      stimulated cell growth both in primary and secondary cultures. The ability of
      serum-starved cells to synthesize DNA after exposure to platelet-derived growth
      factor or serum was also restrained. Notably, the drugs could be added several
      hours after the mitogens without loss of effect, suggesting that they did not
      prevent the entrance into but rather the progression through the cell cycle.
      Accordingly, the expression of early response genes like c-fos, c-jun and c-myc
      was not blocked by the drugs. On the other hand, HMBA reduced the expression of
      transcripts for smooth muscle alpha-actin, type IV collagenase, collagen type I,
      and osteopontin both in primary and secondary cultures. Weaker and more variable
      effects were obtained with MIBG. Taken together, the findings support the notion
      that poly- and mono-ADP-ribosylation of proteins are involved in the control of
      smooth muscle cell differentiation and growth.

PMID- 8575647
TI  - Desmin expressing nonhematopoietic liver cells during rat liver development: an
      immunohistochemical and morphometric study.
AB  - The expression and cellular distribution of desmin, alpha-smooth muscle actin (A
      SMA) and cytokeratin no. 8 (CK-8) and no. 18 (CK-18) in normal adult, neonatal
      and fetal rat liver were examined immunohistochemically on cryostat sections. At
      days 14 and 15 of gestation, nonhematopoietic cells in embryonic liver were
      strongly desmin-positive, and some of the cells, mainly located in the periphery,
      were also stained with anti-A-SMA. Desmin immunoreactivity gradually decreased
      from day 16 of gestation. A close association of desmin-positive cell processes
      with hematopoietic cells was observed during fetal and early neonatal
      development. From day 16 of gestation the pre-hepatocytes became desmin-negative,
      remained CK-8 and CK-18 positive. Desmin-expressing cells were numerous in the
      liver from the embryonic period to the neonatal age. However, their absolute
      number per unit area, as well as their number relative to hepatocytes, decreased
      with age. We suggest that desmin-positive cells in embryonic liver may act as
      stromal cells in the hepatic hematopoietic microenvironment and support
      hepatocyte development.

PMID- 8575648
TI  - Heterogeneity in the progeny of single human muscle satellite cells.
AB  - We examined whether freshly isolated (native) human muscle satellite cells
      (HMSC), as well as their proliferating clonal progenies, were heterogeneous. We
      studied the expression of the cytoskeletal proteins, desmin (DSM), alpha
      sarcomeric and alpha-smooth muscle actins (alpha-SR actin, alpha-SM actin), three
      markers that may be expressed prior to the fusion process. We found that native
      HMSC constituted a homogeneous population of cells expressing desmin and giving
      rise to similar clones in vitro. The clonal progeny of HMSC was heterogeneous,
      including several subpopulations of myoblasts with different cytoskeletal
      phenotypes, commitment states and fusion abilities. A major subpopulation that
      expressed both alpha-sarcomeric actin and desmin during the proliferative stage
      corresponded to a "predifferentiated" population of myoblasts, committed to
      fusion. Another subpopulation, expressing exclusively desmin, and phenotypically
      similar to native HMSC, failed to fuse under fusion-promoting conditions and
      could represent a new generation of HMSC born in culture.

PMID- 8575649
TI  - Receptor-mediated endocytosis of insulin in lower vertebrates: internalization
      and intracellular processing of 125I-insulin in isolated hepatocytes of lamprey
      and frog.
AB  - The binding of 125I-insulin to cellular insulin receptors and the internalization
      of insulin-receptor complexes have been studied in isolated hepatocytes of frog
      and lamprey. Two classes of binding sites (Kd 10(-9) and 10(-8) M) were found in
      cells of both species. The molecular weight of the insulin receptor alpha-subunit
      was 130 kDa in both species. Internalization of bound 125I-insulin in both
      species was found in the temperature range 0 to 20 degrees. Cells "loaded" with
      125I-insulin were used to estimate the fate of the internalized ligand. Release
      of internalized ligand from frog cells increased at temperatures ranging from 0
      to 20 degrees. At 0 degrees the degraded 125I-insulin was 5%, at 5 degrees 7%,
      and at 20 degrees 17% of total radioactivity accumulated in the medium. In
      lamprey hepatocytes there was neither radioactivity accumulation in the
      incubation medium nor release from cells at all temperatures studied. The
      intracellular degradation of internalized 125I-insulin in frog hepatocytes was
      much lower than that in lamprey cells. In frog hepatocytes the specific binding
      of 125I-insulin was increased twofold in the presence of the lysosomal inhibitor
      chloroquine. In contrast no increase was found in lamprey hepatocytes. In
      conclusion, the processing pathways of internalized insulin in the cells of
      ectothermal and endothermal vertebrates are generally similar but in ectothermal
      animals all events take place at lower temperatures and at lower rates. The
      peculiarities of insulin processing in lamprey hepatocytes most likely result
      from the transformation of hepatocytes during the nonfeeding prespawning period.

PMID- 8575650
TI  - Insulin receptor downregulation in isolated hepatocytes of river lamprey
      (Lampetra fluviatilis).
AB  - Insulin receptor downregulation in the isolated hepatocytes of lamprey (Lampetra
      fluviatilis) was studied at the ambient temperature for this species.
      Preincubation of hepatocytes with 10(-9)-10(-8) M unlabeled insulin decreased
      insulin binding capacity to 43, 37, and 34% at 4, 15, and 25 degrees,
      respectively. Preincubation of hepatocytes in the presence of 10(-10) M unlabeled
      insulin had no effect on the 125I-insulin binding. The maximal decrease in the
      125I-insulin binding was reached after 10 min of preincubation and was then
      maintained at a constant level for 2 hr. Competitive binding assays demonstrated
      that preincubation with unlabeled insulin resulted in a 45% decline in the number
      of binding sites. In rat adipocytes and frog hepatocytes used for the comparison,
      preincubation with insulin caused a 65% decrease in cell-surface receptors, while
      intracellular (internalized receptors) increased proportionally. In contrast, in
      the lamprey hepatocytes both cell-surface and intracellular receptors decreased.
      We conclude that insulin receptors of the lamprey hepatocytes could be down
      regulated at the ambient temperature for the species and at the physiological
      concentrations of insulin (10(-9)-10(-8) M).

PMID- 8575651
TI  - Gonadal in vitro androstenedione metabolism and changes in some plasma and
      gonadal steroid hormones during sex inversion of the protandrous sea bass, Lates
      calcarifer.
AB  - Steroidogenesis in the gonad of the protandrous sea bass, Lates calcarifer, was
      examined in vitro in spermiating testis, previtellogenic ovary, and transitional
      gonads. Gonadal tissues were incubated with tritiated androstenedione.
      Metabolites were analyzed by thin-layer chromatography, high-performance liquid
      chromatography, microchemical reactions, and crystallization to constant specific
      activity. 17 beta-Hydroxysteroid dehydrogenase, 5 beta-reductase, and 3 alpha
      hydroxysteroid dehydrogenase activities were found in all of the sex types. On
      the other hand, 11 beta-hydroxysteroid dehydrogenase and 11 beta-hydroxylase
      activities were found only when testicular tissue was present, i.e., in testis
      and early transitional gonad. A low aromatase activity leading to estrone
      synthesis was detected in the previtellogenic ovary. In late transitional gonads,
      a major metabolite (metabolite X) was suggestively identified as a 3-ester of 17
      beta-estradiol according to its chemical and immunological characteristics.
      Levels of 17 beta-estradiol (E2), the metabolite X, testosterone (T), and 11
      ketotestosterone (11KT) were also measured by radioimmunoassay in plasma, before
      (January and February) and during (March and April) the sex inversion process.
      Plasma E2 was virtually undetectable (means below 25 pg/ml), although higher
      levels of metabolite X were found in transitional fish (485 +/- 432 pg/ml in
      March). Throughout this period, plasma levels of T and 11KT and the
      androgens/estrogens ratio were significantly higher in males than in transitional
      fish, where these levels decreased during the sex inversion period. The level of
      in vitro synthesis of metabolite X was high in transitional gonads, but their
      concentrations were very low (0.07 +/- 0.09 ng of equivalent E2/g in transitional
      gonads against 0.22 +/- 0.37 ng of equivalent E2/g in testes and 2.16 +/- 2.7 ng
      of equivalent E2/g in ovaries).

PMID- 8575652
TI  - The relative effectiveness of androstenedione, testosterone, and estrone,
      precursors to estradiol, in sex reversal in the red-eared slider (Trachemys
      scripta), a turtle with temperature-dependent sex determination.
AB  - In many turtles the temperature during the middle of incubation determines the
      gonadal sex of the hatchling. Sex steroid hormones have been implicated in
      temperature-dependent sex determination in the red-eared slider turtle, Trachemys
      scripta; androgen is involved in male sex determination and estradiol in female
      sex determination. Administration of exogenous estradiol and its agonists to eggs
      incubating at a male-producing temperature can overcome the effect of temperature
      and result in all-female offspring. Exogenous testosterone will also result in
      some female hatchlings if administered to eggs incubated at a male-producing
      temperature, an effect due to the aromatization of testosterone to estradiol.
      This study demonstrates that in the red-eared slider, androstenedione, the
      precursor to both testosterone and estradiol, has a similar effect. In addition,
      both testosterone and androstenedione synergize with incubation temperature to
      exert a greater effect at intermediate incubation temperatures that normally
      produce mixed sex ratios, indicating that as with estradiol, androstenedione and
      testosterone are involved in the final common pathway of sex determination in
      this species. At the single dosage administered, estrone and estradiol produced
      all females at a male-producing incubation temperature.

PMID- 8575653
TI  - Sulfated 17,20 beta-dihydroxy-4-pregnen-3-one functions as a potent and specific
      olfactory stimulant with pheromonal actions in the goldfish.
AB  - This study demonstrates that in addition to using the maturational steroid
      hormone 17,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) as a potent sex
      pheromone, the goldfish uses its sulfated metabolite 17,20 beta-dihydroxy-4
      pregnen-3-one 20-sulfate (17,20 beta-P-20S). As measured by electro-olfactogram
      recording (EOG), the goldfish olfactory epithelium is extremely sensitive to both
      free and sulfated 17,20 beta-P (detection thresholds of approximately 10(-12) and
      10(-11) M) but not to glucuronidated or phosphated 17,20 beta-P. Furthermore,
      both structure-activity and cross-adaptation studies using EOG indicated that
      17,20 beta-P-20S and 17,20 beta-P are detected by different olfactory receptor
      sites, suggesting that these cues function as a distinguishable mixture. Finally,
      although the pheromonal activity of 17,20 beta-P-20S appears to be slightly less
      than that of 17,20 beta-P, it too stimulates gonadotropin release and sperm
      production in male goldfish. The precise function of 17,20 beta-P-20S remains
      somewhat enigmatic, however, because it does not appear to enhance the actions of
      17,20 beta-P and is released by a different mechanism. In any case, our findings
      clearly establish that a fish olfactory system can detect particular conjugated
      steroidal compounds in a highly specific manner and that naturally released
      conjugated steroids can function as components of a pheromonal mixture.

PMID- 8575654
TI  - Immunohistochemical identification and morphometric study of ACTH cells of mink
      (Mustela vison) during growth and different stages of sexual activity in the
      adult.
AB  - The morphological characteristics and changes in the cellular area and volume
      density of ACTH cells have been examined in the mink from the first half of the
      suckling period to adulthood and in the adult mink at different stages of the
      sexual cycle. ACTH cells were identified immunohistochemically (avidin-biotin
      complex) and applied over semithin sections. Unlike in suckling and prepubertal
      mink, there was a clear topographic relation between adenohypophysial follicles
      and ACTH cells in pubertal and adult animals. The ACTH cells presented a
      morphological pleomorphism, appearing from oval or round to stellate or angular.
      The morphometric study demonstrated that the cellular area and volume density of
      ACTH cells varied during growth and in adult mink there were sexual variations.
      Gonadal steroids may influence ACTH cells especially in females, in which there
      were variations before and after puberty. The heterogeneity in size, shape,
      secretion, and storage parameters of the ACTH cells could explain the presence,
      in some of the groups studied, of an increased or decreased cellular area, while
      the volume density remained unchanged.

PMID- 8575655
TI  - Intraduodenal fat and amino acids activate gallbladder motility in the rainbow
      trout, Oncorhynchus mykiss.
AB  - The effects on gall bladder motility of intraduodenal injections of fat (cod
      liver oil) and amino acids were investigated in rainbow trout, Onchorhynchus
      mykiss, in vivo. Fat (1 ml/kg, 15 min) increased basic tonus of the gallbladder
      by 79% and frequency of contractions by 53%; both effects were antagonized by
      pretreatment with atropine (1.2 mg/kg). The amino acid mixture similarly
      increased tonus and frequency of contractions of the gallbladder smooth muscle by
      63 and 109%, respectively. The effects were mimicked by intraarterial infusion of
      cholecystokinin (100 pmol-1 nmol/kg-hr). It is concluded that the presence of oil
      and amino acids in the duodenum stimulates rainbow trout gallbladder motility and
      tension, possibly by a release of cholecystokinin, and that the effect of oil, as
      for cholecystokinin, involves a cholinergic pathway.

PMID- 8575656
TI  - Effect of acute captivity stress on plasma concentrations of corticosterone and
      sex steroids in female whistling frogs, Litoria ewingi.
AB  - Plasma concentrations of corticosterone and sex steroids were examined in
      vitellogenic frogs (litoria ewingi) at 0, 0.5, 3, and 24 hr after capture from
      the wild. Plasma corticosterone concentrations were undetectable (< 1.8 ng/ml) in
      all frogs at capture and rose significantly as time in captivity increased (P <
      0.05). Plasma concentrations of estradiol (1001 +/- 13 pg/ml) and testosterone
      (4.0 +/- 0.7 ng/ml) did not change after capture (P > 0.05). Plasma progesterone
      concentration varied slightly after capture (P = 0.046) but this was of doubtful
      significance. Concentrations of corticosterone did not significantly correlate
      with estradiol, testosterone, or progesterone concentrations during 0-24 hr after
      capture. These results and previous studies indicate considerable variation among
      the sex steroid responses of female amphibians to capture. We suggest that the
      stage of vitellogenesis may modulate the amphibian response to captivity stress.

PMID- 8575657
TI  - The role of the renin-angiotensin system in the control of blood pressure and
      drinking in the European eel, Anguilla anguilla.
AB  - The role of the renin-angiotensin system (RAS) in the control of blood pressure
      and drinking was investigated in fresh water (FW)- and seawater (SW)-adapted
      eels, Anguilla anguilla, by comparing the effects of pharmacological manipulation
      through the use of papaverine (stimulator) and captopril (inhibitor) on the
      endogenous system. In SW eels basal blood pressure levels were lower (23.3 +/-
      0.8 mm Hg) with correspondingly higher basal drinking rates (0.51 +/- 0.07
      ml/kg/hr) and plasma AII concentrations (32.89 +/- 4.19 fmol/ml) compared to FW
      eels (33.8 +/- 1.3 mm Hg, 0.06 +/- 0.02 ml/kg/hr, 9.72 +/- 0.60 fmol/ml,
      respectively). In FW eels papaverine caused immediate hypotension with full
      recovery, decrease in plasma osmolality, and increase in drinking rate and plasma
      AII concentration, but in SW eels, hypotension with full recovery and an increase
      in plasma osmolality, drinking rate, and plasma AII concentration occurred. In FW
      eels captopril had no effect on the parameters measured, but in SW eels it caused
      a sustained decrease in blood pressure and a decline in the basal drinking rate
      and plasma AII concentration. Papaverine was also administered 15 min after
      captopril. In FW eels this manipulation caused hypotension only after the
      papaverine injection, followed by a partial recovery. Osmolality was unaffected,
      the previously observed papaverine-induced dipsogenic response was blocked, and
      the rise in plasma AII concentrations was smaller than with papaverine only. In
      SW eels there was an immediate hypotension after captopril administration with
      full recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8575658
TI  - Effect of various vitamin D metabolites on serum calcium and inorganic phosphate
      in the freshwater snake Natrix piscator.
AB  - Vitamin D3 (650 pmol and 6.50 nmol/100 g body wt), 25-hydroxyvitamin D (650 pmol
      and 6.50 nmol/100 g body wt), and 1,25-dihydroxyvitamin D (65 pmol and 650
      pmol/100 g body wt) were administered daily to the freshwater snake Natrix
      piscator for 15 days. Both serum calcium and inorganic phosphate levels were
      increased significantly in all of the treated groups. This is the first report of
      hypercalcemia and hyperphosphatemia in reptiles induced by 25-hydroxyvitamin D
      and 1,25-dihydroxyvitamin D.

PMID- 8575659
TI  - Steroid-induced sex determination at incubation temperatures producing mixed sex
      ratios in a turtle with TSD.
AB  - Previous studies have shown that exogenous steroid hormones can affect sex
      determination in reptiles with temperature-dependent sex determination (TSD).
      These studies have also suggested that the sensitivity of TSD to exogenous
      steroids may vary with incubation temperature. The majority of these studies,
      however, have utilized incubation temperatures producing all males or all females
      in the control groups, rather than temperatures which produced mixed sex ratios
      in control groups. The goals of the current study were to examine the effects of
      steroids on sex determination in a turtle (Trachemys scripta) at temperatures
      which produced mixed sex ratios in the control groups. Collectively, the results
      of single-treatment experiments indicate that at incubation temperatures
      producing mixed sex ratios in control groups, (1) estradiol-17 beta, tamoxifen,
      norethindrone, and testosterone all showed a similar "type" of effect (i.e.,
      feminizing) as in previous studies utilizing male-producing temperatures, (2) sex
      determination has significantly increased sensitivity to estradiol-17 beta in
      comparison to its effect at temperatures producing all males, and (3) sex
      determination is sensitive to the masculinizing effects of dihydrotestosterone
      (DHT) (in previous studies utilizing female-producing temperature DHT did not
      affect sex determination). Last, a set of double-treatment experiments was
      performed in which eggs received both estradiol-17 beta and DHT treatments. No
      significant increases in the production of males were detected. Significant
      increases in the production of females were detected, but only in the groups
      receiving the highest dosage of estradiol-17 beta (1.0 micrograms).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8575660
TI  - Atrial natriuretic peptide gene expression within invertebrate hearts.
AB  - The present investigation was designed to (1) determine if atrial natriuretic
      factor gene expression occurs within invertebrates as well as within vertebrates;
      (2) determine whether the product of this gene expression is the 126-amino-acid
      atrial natriuretic factor prohormone or some other molecular species; and (3)
      evaluate within the same invertebrates if the products of atrial natriuretic
      factor gene expression are released into their circulation. Utilizing a very
      sensitive RNase protection assay it was found that atrial natriuretic peptide
      gene expression occurs within the heart of the oyster, Crassostrea virginica, and
      within the heart of the blue crab, Callinectes sapidus, but was expressed
      sevenfold less than in a vertebrate heart (i.e., rat, Rattus norvegiucs). High
      performance gel-permeation chromatography followed by N-terminal and C-terminal
      atrial natriuretic factor prohormone radioimmunoassays indicated that the
      molecular species synthesized within the oyster and blue crab hearts was the
      atrial natriuretic factor prohormone. The product(s) of this atrial natriuretic
      factor gene expression (i.e., atrial natriuretic peptides) was found to be
      released into the circulation, i.e., hemolymph, of both the oyster and the blue
      crab.

PMID- 8575661
TI  - D-aspartate in the male and female reproductive system of Octopus vulgaris lam.
AB  - Free D-aspartate (D-Asp) has been previously found in the nervous system of
      Octopus vulgaris (Mollusca: Cepalopoda) and has recently also been found in many
      endocrine tissues of the rat. The present study examined whether this enantiomer
      also occurs in the reproductive system and the brain of the octopus. In this
      mollusk, D-aspartate was present in both the male and the female reproductive
      systems. In males, it was found at high concentrations in the prostate, vas
      deferens, Needham's sac, and testis. In females, a high concentration was found
      in the oviduct, accessory nidamental gland, and ovary. The concentration varied
      between 0.4 and 2.9 mumol/g wet tissue, which corresponds to a percentage of D
      Asp/total D+L-Asp between 7 and 33%. No appreciable quantities of D-Asp were
      found in the digestive, excretory, circulatory, and muscular systems, indicating
      that in the octopus this enantiomer may play a role in both the nervous and the
      reproductive systems.

PMID- 8575662
TI  - Photoperiod regulation of plasma growth hormone levels during parr-smolt
      transformation of Atlantic salmon: implications for hypoosmoregulatory ability
      and growth.
AB  - The influence of photoperiod on plasma growth hormone (GH) levels during parr
      smolt transformation was studied in Atlantic salmon, using a specific salmon GH
      radioimmunoassay; in addition, the impact of endogenous changes in GH levels on
      hypoosmoregulatory ability and growth was assessed using seawater challenge tests
      and measurements of growth rates. Groups of fish were kept on simulated natural
      photoperiod or continuous light, and subgroups were subjected to reciprocal
      transfers between these two light regimes at different times. For Atlantic salmon
      on simulated natural photoperiod, GH levels increased during the parr-smolt
      transformation, from 0.6 ng ml-1 in January-March to 6.6 ng ml-1 in June, while
      the corresponding change in fish on continuous light was from 0.4 to 1.0 ng ml-1.
      The study demonstrates that photoperiod is a major zeitgeber for the increased GH
      levels during the parr-smolt transformation of Atlantic salmon. The data further
      support the view that exposure to continuous light into fall and winter causes a
      "free running" of an endogenous rhythm governing smolting and a subsequent phase
      delay of the parr-smolt transformation-related increase in plasma GH levels. A
      strong positive nonlinear correlation was found between specific growth rate and
      GH levels, with growth rate increasing rapidly with increasing GH levels up to 2
      3 ng ml-1 at which point near-maximal growth rate is reached, revealing that
      relatively small increases in GH levels may be of great importance for an
      increased specific growth rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8575663
TI  - Neuroendocrine control of osmotic regulation in the freshwater shrimp
      Macrobrachium olfersii (Wiegmann) (Crustacea, decapoda): free amino acid
      concentrations in the hemolymph.
AB  - The participation of neuroendocrine factors present within the central nervous
      system in the regulation of hemolymph free amino acid (FAA) concentrations was
      examined in the freshwater shrimp Macrobrachium olfersii. Test shrimps were
      injected intramuscularly with homogenates prepared from the eyestalks (ES),
      ventral nerve cord (VNC), supraesophageal (SEG), or thoracic ganglia (TG) of
      donor shrimps previously exposed for 6 hr to a high-salinity medium (HSM, 21%
      salinity). After injection of the homogenate, the shrimps were maintained for up
      to 6 hr in either freshwater (FW) or HSM. Hemolymph was sampled by cardiac
      puncture and prepared for reverse phase HPLC, derivatizing the FAA with
      phenylisothiocyanate. An FAA profile was determined and the [FAA]:[Cl-] ratios
      for the four FAA present in highest concentration (Gly, Arg, Ala, and Pro for ES
      and VNC experiments; Glu, Leu, Ala, and Val for SEG and TG experiments) were
      obtained. Nonparametric analyses revealed specific, notable effects resulting
      from homogenate injection, e.g., ES homogenate increased [Pro]/[Cl-] ratios in FW
      exposed shrimps; SEG homogenate increased [Glu]/[Cl-] and [Val]/[Cl-] ratios in
      HSM-exposed shrimps; and TG homogenate increased [FAA]/[Cl-] ratios for Glu, Leu,
      Ala, and Val in HSM-exposed shrimps. Total FAA concentrations decreased after
      exposure of the shrimps to HSM but were increased by the injection of ES
      homogenate in FW-exposed shrimps and by TG homogenate in HSM-exposed shrimps. The
      total [FAA]/[Cl-] ratio was also increased by TG homogenate in HSM-exposed
      animals. There were no clear effects on [Cl-] alone.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8575664
TI  - Photoperiodic effects on steroid negative feedback in female prairie voles
      (Microtus ochrogaster).
AB  - Breeding in prairie voles is mainly restricted to the autumn and winter of most
      years. The organization of estrus in female prairie voles is unusual because
      behavioral estrus is induced by chemosensory stimuli from the urine of adult
      conspecific males. Isolated females exhibit undetectable levels of estradiol and
      never display estrous behavior, yet exposure to male urine causes a cascade of
      endocrine changes that evoke estrogen secretion from the ovaries and estrous
      behavior within 24 hr. In the prairie vole, the extreme dependence of estrus on
      chemosensory stimuli raises the possibility that their ovaries may be less
      prominent in the regulation of gonadotropin secretion than in species with more
      endogenously organized estrous cycles. The present study examined the
      contribution of the ovaries in luteinizing hormone (LH) regulation in prairie
      voles. Females were maintained for 9 weeks in either long (LD 16:8) or short (LD
      8:16) photoperiodic conditions, a blood sample was obtained, and then animals
      were either ovariectomized or received a sham procedure. Another blood sample was
      obtained a week later and assayed for serum LH. Blood serum LH levels were
      significantly reduced in short-day voles, compared to long-day animals. After
      ovariectomy both long-day and short-day voles exhibited equivalent elevations in
      LH levels. This study provides evidence that photoperiod is measured in female
      voles and the ovaries appear to produce sufficient steroids to suppress LH
      release.

PMID- 8575665
TI  - Characterization of insulin, glucagon, and somatostatin from the river lamprey,
      Lampetra fluviatilis.
AB  - Insulin has been isolated from an extract of the pancreas of an Agnathan, the
      river lamprey Lampetra fluviatilis. The primary structure of the peptide (A
      chain: GIVEQ CCHRK CSIYD MENYC N; B-chain: SALTG AGGTH LCGSH LVEAL YVVCG DRGFF
      YTPSK T) is the same as that of insulin from the sea lamprey Petromyzon marinus.
      In contrast, Lampetra glucagon (HAQGS FTSDY SKYLD SKQAK DFVIW LMNT), isolated
      from an extract of intestine, is structurally more similar to human glucagon
      (five amino acid substitutions) than to Petromyzon glucagon (six substitutions).
      Similarly, the primary structure of somatostatin (AAAAP GAAGG AQLPL GNRER KAGCK
      NFFWK TFSSC), isolated from Lampetra pancreas, contains eight amino acid
      substitutions and an additional residue compared with Petromyzon somatostatin.
      Somatostatin, isolated from Lampetra brain, has an identical structure to
      mammalian somatostatin-14 (AGCKN FFWKT FTSC), indicative of the same tissue
      specific expression of different somatostatin genes that was previously observed
      in Petromyzon. In contrast to the reduced binding affinity of other fish
      insulins, lamprey insulin was equipotent with porcine insulin in inhibiting the
      binding of [3-[125I]iodotyrosine-A14] human insulin to the human insulin
      receptor.

PMID- 8575666
TI  - Rates of change of genetic parameters of body weight in selected mouse lines.
AB  - A method based on the animal model is described which allows the estimation of
      continuous changes in variance components over time using restricted maximum
      likelihood (REML). The method was applied to the analysis of a selection
      experiment in which a foundation population formed from a cross between two
      inbred strains of mice (C57BL/6J and DBA/2J) was divergently selected for 6 week
      body weight over 20 generations. The analysis suggested that there was an
      increase in phenotypic variance of about 50% in the low selected lines over the
      course of the experiment which was attributed to increases in the environmental
      and additive variance components. Variance changes in the High selected lines
      were generally smaller than in the Low lines, although there was an estimated 20%
      increase in the environmental variance. Simple models to explain these effects
      involving dominance, linkage and epistasis were explored. Testing which of these
      was responsible for the variance changes noted in this experiment (if any) is
      difficult, although the epistasis and dominance models require less stringent
      conditions than the linkage model, and the dominance model is supported by
      evidence of heterosis in the F1.

PMID- 8575667
TI  - Behavioural changes as a correlated response to selection.
AB  - Lines of mice have been selected for up to 50 generations on the following
      traits: high body weight, low body weight, high fat content or low fat content.
      The lines selected for high or low body weight differ by a factor of 2.5 and
      those selected for high or low fat content differ by a factor of five, both
      traits measured in 10 week old males. A set of behavioural traits was measured to
      ascertain whether this selection had caused correlated responses in behaviour:
      studies included feeding behaviour, open field behaviour, ultrasound calling
      rates of pups, and the response to the introduction of a novel physical object.
      Alterations in behavioural patterns which were expected a priori were observed
      but there appeared to be no changes in behaviour associated with any one
      selection criterion. Estimates of the genetic correlations between selected and
      behavioural traits were, with one exception, generally less than 0.1 in magnitude
      and not significantly different from zero (the exception was food intake in lines
      selected on body weight). Assuming that mice are accurate models for commercial
      species, then these results have important implications for animal welfare: they
      demonstrate that large scale behavioural changes do not arise as an inevitable
      consequence of intense long-term selection on traits of economic importance in
      commercial species.

PMID- 8575668
TI  - Pattern and frequency of nocodazole induced meiotic nondisjunction in oocytes of
      mice carrying the 'tobacco mouse' metacentric Rb(16.17)7Bnr.
AB  - Oocytes from (C3H/HeH x 101/H)F1 and Rb(16.17)7Bnr homozygous females were
      exposed to a range of doses of nocodazole in vitro. The spindle poison caused a
      dose dependent increase in metaphase I (MI) arrest and hyperploidy. A
      concentration of 0.03 microgram/ml was found to induce a maximum hyperploid
      frequency of 3.1% and 11.6% respectively without a high level of MI arrest.
      Between 0.03 and 0.05 microgram/ml MI arrest increased substantially and reached
      a frequency of approximately 90%. In a further experiment oocytes from Rb7
      homozygous, heterozygous and 3H1 females were exposed to 0.03 microgram/ml
      nocodazole 4, 6 or 8 h after the onset of maturation. The phase at which the
      spindle was inhibited resulted in a specific pattern of nondisjunction which in
      turn was dependent on whether the female carried an Rb metacentric. 3H1 oocytes
      gave a normally distributed pattern of increase in aneuploid frequency (over the
      spontaneous value) centering around a 6 h application. This was thought to be due
      to the interaction of chromosomes with the microtubules of the spindle during
      attachment and/or alignment. In contrast both Rb homozygotes and heterozygotes
      gave the same biphasic response, with a high frequency of aneuploidy in the
      oocytes when nocodazole was applied 4 and 8 h after the onset of maturation. In
      Rb homozygotes we demonstrated that the Rb bivalent underwent nondisjunction more
      frequently than the average acrocentric, when nocodazole was administered
      early.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8575669
TI  - Low rates of proviral integration in SWR/J-RF/J hybrid mice.
AB  - A high frequency of proviral acquisition has previously been reported in the
      offspring of SWR/J-RF/J hybrid mice. In the present study, it was investigated
      whether this proviral acquisition would be useful for large-scale insertional
      mutagenesis studies. A population of SWR/J-RF/J hybrid mice with a predominantly
      SWR/J background was created. Lines of mice with such a background and partially
      congenic for two active proviruses from the RF/J strain were generated (the
      insert lines). Control lines were derived from mice which had no proviral loci
      but had an otherwise similar genetic background. DNA samples of mice in the
      insert lines were screened for the appearance of new proviral loci by Southern
      hybridization. The rate of proviral acquisition, calculated from the observed
      number of new proviral loci was 0.023 new proviruses per mouse. This rate is
      lower than found in previous studies and too low for large-scale insertional
      mutagenesis studies. A sensitivity experiment indicated that there was adequate
      detection of new proviral loci. The number of segregating proviruses was
      consistent with the number of newly acquired proviruses actually detected. Two
      additional crosses between mice in the insert lines and SWR/J mice were
      performed. The rate of proviral acquisition was greatly increased when SWR/J
      females were initially mated to insert mice, but remained unchanged when SWR/J
      males were used. This suggested that mice in the insert lines had acquired a
      maternally transmitted factor, which was suppressing viral expression and thus
      reducing the rate of proviral acquisition.

PMID- 8575670
TI  - Marker assisted selection for genetic improvement of animal populations when a
      single QTL is marked.
AB  - A Monte Carlo simulation study to evaluate the benefits of marker assisted
      selection (MAS) in small populations with one marked bi-allelic quantitative
      trait locus (QTL) is described. In the base generation, linkage phase equilibrium
      between the markers, QTL and polygenes was assumed and frequencies of 0.5 for the
      two QTL alleles were used. Six discrete generations of selection for a single
      character measured on both sexes followed. An additive genetic model was used
      with the QTL positioned midway between two highly polymorphic markers. Schemes
      were simulated with a distance of 10 cM between the QTL and either of the two
      markers and with the QTL explaining 1/8 of the total genetic variance in the base
      generation. Values of 0.5, 0.25 or 0.1 were assumed for the heritability. Eight
      males and 16, 32 or 64 females were selected each generation with each dam
      producing four sons and four daughters as candidates for the next generation.
      Animals were evaluated with a conventional BLUP animal model or with a model
      using marker information. MAS resulted in substantially higher QTL responses (4
      54%), especially with low heritabilities, than conventional BLUP but lower
      polygenic responses (up to 4%) so that the overall effect on the total genetic
      response, although in the majority of cases favourable, was relatively small.
      With QTLs of larger size (explaining 25% of the genetic variance) comparable
      results were found. When the distance between the QTL and the markers was reduced
      to 2 cM, genetic responses were increased very slightly with a heritability of
      0.5 whereas with a heritability of 0.1 responses were increased by up to 10%,
      compared with conventional BLUP. Results emphasize that MAS should be most useful
      for lowly heritable traits and that once QTLs for such traits have been
      identified the search for closely linked polymorphic markers should be
      intensified.

PMID- 8575671
TI  - Population structure, fitness surfaces, and linkage in the shifting balance
      process.
AB  - Wright first introduced the idea that random genetic drift and classical mass
      action selection might combine in such a way as to allow populations to find the
      highest peak in complicated adaptive surfaces. His theory assumes large but
      structured populations, in which mating is spatially local. If gene flow is
      sufficiently low, and the subpopulations (demes) are small enough, they will be
      subject to genetic drift. Distant demes drift independently, allowing many
      independent searches of the adaptive surface to take place. A deme that has
      shifted to a higher peak can, by emigration, cause the rest of the demes to shift
      to the higher peak. The probability of this shift depends on the migration rate.
      Previous studies have concluded that very little migration is necessary to effect
      the shift in adaptive peaks that characterizes the last phase of Wright's
      Shifting Balance Process (SBP). Here we present the results of a computer study
      that investigates the roles of dispersal distance, the degree of epistasis in the
      fitness surface, and recombination on the shifting balance process. In
      particular, we measure their effect on the population's mean fitness. We show
      that over a range of dispersal distances the advantage of the SBP is a
      monotonically increasing function of the amount of epistasis. Our results show
      that the extent of dispersal that results in the greatest effect of the SBP in
      increasing mean fitness depends on the extent of epistasis. Finally, for low
      levels of epistasis, higher recombination performs better, while for intermediate
      levels, lower recombination results in a greater advantage of the SBP.

PMID- 8575672
TI  - Two independent cis-acting elements regulate the sex- and tissue-specific
      expression of yp3 in Drosophila melanogaster.
AB  - In Drosophila, the three yolk protein (yp) genes are transcribed in a sex-,
      tissue- and developmentally specific manner, providing an ideal system in which
      to investigate the factors involved in their regulation. The yolk proteins are
      synthesized in the fat body of adult females, and in the ovarian follicle cells
      surrounding the developing oocyte during stages 8-10 of oogenesis. We report here
      an analysis of the yolk protein 3 (yp3) gene and its flanking sequences by means
      of P-element mediated germ-line transformation and demonstrate that a 747 bp
      promoter region is sufficient to direct sex-specific expression in the female fat
      body and both the temporal- and cell-type-specificity of expression during
      oogenesis. Two elements that independently govern yp3 transcription in these
      tissues have been separated and no other sequences in the upstream, downstream or
      coding regions have been identified that are autonomously involved in yp3
      expression.

PMID- 8575673
TI  - [Use of CO2 laser in the treatment of condylomata acuminata of the anogenital
      region in pregnant women].
AB  - The first results of treatment of condylomata acuminata of anogenital region in
      11 pregnant women were presented. The analysis were made in Department of
      Reproduction, Institute of Gynecology and Obstetrics, Academy of Medicine,
      Poznan. All patients were treated between 28 and 35 week of pregnancy. After
      first laser-therapy the healing achieved in 9 women. The second lasertherapy was
      required in 2 patients. It was done after 3 weeks. Complete destruction of
      pathological changes was obtained. All women had vaginal delivery and no
      complications (connected with HPV infection) in their newborns were found. The
      authors said that CO2-lasertherapy under colposcopic control is a reliable method
      for treatment of condylomata acuminata in pregnant women.

PMID- 8575674
TI  - [Uterine myomectomy in the treatment of infertility].
AB  - Modern operative methods of myomectomy in women treated because of sterility are
      shown, with pointing these methods in which possibilities of post-operative
      adhesions and loss of blood are decreased. Also laparoscopic methods with use of
      laser are shown.

PMID- 8575675
TI  - [A quantitative analysis of uterine contraction during labor].

PMID- 8575676
TI  - [Prophylaxis of puerperal infections using the Gyno-Pevaryl 150 preparation].
AB  - The authors estimated the biocenosis of vagina in women before delivery. The
      examination were made upon 50 women between 28 and 40 week of pregnancy and on
      the third day after delivery; comparing the results of estimation the purity of
      vagina and bacterial inoculations in two groups of pregnant women:-control group
      (without G-P 150 treatment) and in group with G-P 150 application. The authors
      proved the entire disappearance of mycotic infection (candida albicans) in women
      treated with G-P 150. The also stated that potential pathogenic bacterial flora
      during puerperium occurs much more rarely.

PMID- 8575677
TI  - [Concentration of lipids and lipoproteins in serum of pregnant women with primary
      hypertension].
AB  - The tests have been conducted on 44 women in 3rd trimester of pregnancy. 30 of
      them were the women with a normal course of pregnancy, and 14 were the ones with
      the primary hypertension. The blood serum has been tested for the concentration
      of triglycerides, phospholipids, total cholesterol, HDL and LDL- cholesterol,
      alpha, beta and pre-beta lipoprotein fractions. The results have been calculated
      statistically. It has been found that the increase in the concentration of
      triglycerides (p < 0.001), and the beta lipoprotein fraction (p < 0.004) was
      essentially higher in the women with the primary hypertension in 3rd trimester of
      complicated pregnancy in comparison to those values observed in the healthy
      pregnant women. At the same time a lower concentration of alpha lipoproteins (p <
      0.02) has been observed in the group of the pregnant with the primary
      hypertension. Differences between the concentration of other parameters have not
      obtained statistical significance.

PMID- 8575678
TI  - [Concentration of lipids and lipoproteins in serum of women with pregnancy
      induced hypertension].
AB  - The tests have been carried out on 64 women in 3rd trimester of pregnancy. 30 of
      them were the women with a normal course of pregnancy, and 34 were the ones with
      hypertension induced pregnancy (PIH). Their blood serum has been tested for the
      concentration of TG, phospholipids, total cholesterol, HDL- and LDL-cholesterol,
      alpha, beta and pre-beta lipoprotein fractions. The results have been calculated
      statistically. It has been found that the increase in the concentration of TG (p
      < 0.001), phospholipids (p < 0.02), total cholesterol (p < 0.01), the beta
      lipoprotein fraction (p < 0.001) was essentially higher in the women with PIH, in
      3rd trimester of pregnancy, in comparison to those values observed in the healthy
      pregnant women. At the same time a lower concentration of alpha lipoproteins (p <
      0.01) has been observed in the group of the pregnant with pregnancy induced
      hypertension.

PMID- 8575679
TI  - [Evaluation of a seven year period of managing pregnancies complicated by
      diabetes mellitus].
AB  - The authors have evaluated seven years' period of the intensive care of pregnant
      women suffering from diabetes mellitus. In the analysed period 175 patients
      suffering from diabetes gave birth to babies, and that was 0.69% of all the
      labours. The most frequent type of diabetes was gestational diabetes mellitus
      (53.7%), and diabetes of B type (23.5). Diabetes of G-1 type occurred in as many
      as 44% of the examined women. In the tested group of women the indication to
      conducting a cesarean section occurred in 16.6% of cases. It was found that the
      babies born by the mothers suffering from diabetes had in their early neonatal
      period the following biochemical disorders: hypoglycemia--37.7%,
      hyperbilirubinemia--17.4%, anemia--8.7% and hypocalcemia--5.8% of cases.
      Monitoring of pregnancy, the time and the way of its termination should be
      selected individually for each women suffering from diabetes mellitus.

PMID- 8575680
TI  - [Changes in levels of chorionic gonadotrophin (hCG) and its subunit alpha and
      beta in pregnancy complicated by diabetes (GDM)].
AB  - The aim of the study was estimation of endocrinological function of placenta in
      pregnancy complicated by GDM. The study were performed on a group 13 women with
      GDM and 14 women in normal pregnancy. All women with GDM were treat by diet and
      intensive insulinotherapy with self monitoring levels of glucose. In women with
      GDM level of fructosamine and HbAlc were significant higher but in normal range.
      In 28 and 36 week of pregnancy were determined levels of hCG, alpha hCG, beta
      hCG, in serum. Level of hCG in control group and in women with GDM were
      respectively 97.29 U/ml vs. 29.29 U/ml, p < 0.01 in 28 week of pregnancy and
      77.23 U/ml vs. 37.93 U/ml, p < 0.05 in 36 week. Level of alpha hCG was lower and
      beta hCG was higher in group with GDM.

PMID- 8575681
TI  - [Evaluation of the usefulness and reference values for the amniotic fluid index
      in normal pregnancy between 30 and 42 weeks of gestation].
AB  - The four-quadrant sum of amniotic fluid pockets (amniotic fluid index) was
      studied prospectively in 130 normal pregnancies from 30 to 42 weeks. Statistical
      investigation were used to establish the mean, 95% confidence intervals and
      standard deviations for the AFI at each week of gestation. The AFI value
      decreased since 30 week, especially between 33 and 34 week and after 41 week. The
      AFI value < or = 5 represents oligohydramnios, the AFI value > or = 20
      constitutes polyhydramnios.

PMID- 8575682
TI  - [Hemostatic disturbances in women with unexplained fetal loss].
AB  - 106 women was screened for a lupus anticoagulant. Activated partial
      thromboplastin time, tissue thromboplastin inhibition test and euglobulin lysis
      time was performed. Ten of 61 women (16%) with spontaneous multiple abortions,
      foetal death, intrauterine growth retardation (IUGR) and gestosis had one or two
      pathological results of tests while no one of the 41 women which had no pregnancy
      complication. Significance of difference between this two groups was verified by
      Fischer exact test (P less than 0.05).

PMID- 8575683
TI  - [Contemporary views on estrogen replacement therapy. II. Hormonal therapy in
      women with imminent ischemic heart disease].
AB  - The frequence of ischemic heart disease occurring increases 2-3 fold in
      postmenopausal period. It is a result of serum lipid profile changes.
      Estrogenotherapy restores correct lipid relations and protect coronary vessels in
      this way, preventing stenocardia and cardiac infarcts. Divergent opinions coexist
      with including progestogens to estrogen replacement therapy. However a view that
      well selected doses and kind of hormone effectively enhance serum HDL level,
      begins to prevail.

PMID- 8575684
TI  - [Prognostic value of vaginal ultrasound with color Doppler in differentiating the
      malignancy of ovarian tumors].
AB  - The authors presented results of research on pathological vascularization in
      ovarian tumors by Doppler's method. 60 records of blood flow were analysed to
      estimate: pulsation index (PI) and resistance index (RI). Among benign ovarian
      tumors (26 cases) PI was 1.82 +/- 0.93 and RI 0.93 +/- 0.36. On the contrary, for
      malignant neoplasms (11 cases) the blood flow was low resistance PI: 0.89 +/-
      0.38 and RI: 0.44 +/- 0.19.

PMID- 8575685
TI  - Relationship of endometrial thickness and echo patterns on pregnancy rates in
      patients with luteal phase defects.
AB  - The objective of this prospective comparative study was to investigate the
      relationship of sonographic measurements of the endometrium at the time of peak
      follicular maturation to conception outcome in patients treated for luteal phase
      defects (as determined by out-of-phase endometrial biopsies). Treatments for
      luteal phase defects included progesterone supplementation with or without
      follicle-maturing drugs, depending on whether the patient attained a follicle of
      at least 18 mm and a serum estradiol of > 200 pg/ml. No differences in pregnancy
      rates were found by the thickness of endometrium (< 10 vs. > or = 10 mm) or echo
      pattern in any of the treatment modalities. Thus, contrary to findings in
      stimulated cycles for in vitro fertilization, endometrial thickness at the time
      of peak follicular maturation is not predictive of outcome in patients treated
      for luteal phase defects in natural cycles.

PMID- 8575686
TI  - Clinical, hormonal and sonographic predictors of successful RU-486-induced
      abortions.
AB  - To evaluate which method, clinical, hormonal or sonographic, can be used as the
      best predictor of successful RU-486-induced abortions, 20 healthy women with
      fetal cardiac activity, between 6 and 9 weeks from the last menstrual period and
      desiring abortion, were studied. Fourteen women (70%) successfully aborted, and 6
      (30%) failed to abort within 7 days following therapy. A small hematoma, seen as
      a localized detachment of the gestational sac, was observed in the decidua
      capsularis in women who aborted successfully. A significant decrease in plasma
      levels of estradiol and progesterone (p < 0.04) and significantly increased
      cortisol levels (p < 0.001) in the plasma of the 14 patients who aborted were
      noted by the 7th day following treatment. No significant changes were observed in
      the 6 nonaborting patients. In conclusion, the differences in the early
      sonographic findings may be helpful in the early prediction of successful RU-486
      administration.

PMID- 8575687
TI  - Relationship of endometrial thickness and sonographic echo pattern to
      endometriosis in non-in vitro fertilization cycles.
AB  - The objective of this study was to investigate the effect of endometriosis on the
      proliferation of the endometrium as determined by sonographic measurements of
      endometrial thickness and echo pattern at peak follicular maturation. A
      prospective study of 60 infertility patients was conducted in which the
      endometrium was evaluated sonographically, both before and after laparoscopy.
      Prior to laparoscopy, the mean endometrial thickness was 10.5 +/- 1.9 mm in the
      group without endometriosis (n = 20) and 11.7 +/- 2.8 mm in the group with
      endometriosis (n = 40) (p > 0.05). Following the laparoscopy, there was no change
      in the mean thickness within each group. The incidence of an unfavorable echo
      pattern was negligible in both groups. Endometriosis does not cause a reduction
      in endometrial thickness, nor does it appear to influence the development of an
      unfavorable echo pattern at time of peak follicular maturation.

PMID- 8575688
TI  - Comparison of efficacy of high-dose pure follicle-stimulating hormone versus
      human menopausal gonadotropins for in vitro fertilization.
AB  - The advent of recombinant DNA technology will soon produce for the market a
      product that has pure follicle-stimulating hormone (pFSH) but no luteinizing
      hormone. A prospective randomized study was performed to see if pFSH (Metrodin)
      was able to stimulate the same in vitro fertilization parameters as human
      menopausal gonadotropin when preceded by gonadotropin suppression by leuprolide
      acetate. The results showed similar parameters between the two drugs, i.e.,
      number of oocytes, number of embryos, endometrial thickness at time of human
      chorionic gonadotropin, fertilization rates and pregnancy rates in a protocol
      purposely designed to stimulate as many follicles as safely as possible because
      of a shared oocyte and successful cryopreservation program.

PMID- 8575689
TI  - Epidermal growth factor and transforming growth factor-beta in uterine fibroids
      and myometrium.
AB  - Fibroids (leiomyomata) are the commonest tumours in women, but their aetiology is
      unknown. Epidermal growth factor (EGF) and transforming growth factor-beta (TGF
      beta) may be important factors involved in fibroid growth. We examined the mRNA
      expression of these two growth factors in fibroids and corresponding myometrium
      from 20 women who underwent hysterectomy because of fibroids. We also examined
      these factors in samples of fibroids from 9 women who underwent myomectomy after
      pretreatment with luteinizing hormone-releasing hormone agonists. We found that
      both factors were expressed in the three types of tissue examined. We also found
      that there was no difference in the relative abundance of either of the two
      growth factors between the tissues studied. Despite the lack of difference, we
      postulate that EGF and TGF beta may be important in fibroid growth because of a
      possible interaction between the two factors in this tissue.

PMID- 8575690
TI  - Clinical effects of preoperative oestradiol treatment before vaginal repair
      operation. A double-blind, randomized trial.
AB  - The objective of the study was to assess the effects of low-dose vaginal
      treatment with oestradiol before vaginal operation. In a double-blind randomized
      study including 43 postmenopausal women scheduled for vaginal repair operation
      for genital descensus, it was found that 7 patients suffered from concomitant
      urinary stress incontinence. Vagifem (25 micrograms oestradiol) or placebo was
      administered as vaginal pessaries daily, 3 weeks prior to surgery and the
      clinical effects evaluated. One month postoperatively the prevalence of
      bacteriuria (> 100,000 CFU/ml urine) was significantly lower when using
      oestradiol than in the placebo group. At follow-up 3 years later 40 women (93%)
      answered the questionnaires. None received hormone replacement therapy. Nineteen
      percent in the preoperative oestradiol group and 11% in the preoperative placebo
      group had had more than two episodes of cystitis treated with antibiotics. This
      difference is not statistically significant (p > 0.05). Recurrent cystitis was
      not correlated to bacteriuria postoperatively. Seventy-nine percent of the women
      with genital prolapse but only 29% of the women with concomitant urinary stress
      incontinence were cured (p < 0.05). Neither preoperative oestradiol treatment nor
      body weight had any influence on relapse. Preoperative low-dose vaginal
      oestradiol treatment may reduce the incidence of bacteriuria in the immediate
      postoperative period but no long-lasting effects on recurrent cystitis or relapse
      were seen. Longer-lasting hormone replacement therapy may be necessary to achieve
      lasting effects.

PMID- 8575691
TI  - Influence of menopause on the cell kinetics of normal, hyperplastic, and
      malignant endometrium.
AB  - We investigated whether menopause influences the cell kinetics of normal,
      hyperplastic, and malignant endometrium. As a preliminary step, immunochemical
      staining for proliferation cell nuclear antigen (PCNA) and flow cytometric
      analysis were performed in 25 endometrial specimens. A weak but significant
      correlation between the percentage of PCNA-positive cells and the proliferation
      index indicated that flow cytometric analysis was useful for cell kinetics study.
      Then cell kinetics were analyzed in a total of 198 endometrial specimens by flow
      cytometry. Subjects were classified as premenopausal and postmenopausal. The
      proliferation index and DNA ploidy pattern for each type of endometrium were
      examined in these two groups. The proliferation indices of normal endometrium and
      G1 endometrial cancer were significantly lower in postmenopausal women. The
      aneuploid pattern was detected only in postmenopausal women with endometrial
      cancer. The current results showed that menopause influences the cell kinetics of
      normal endometrium and G1 endometrial cancer.

PMID- 8575692
TI  - Natural killer cell activity in patients with invasive cervical carcinoma:
      importance of a longitudinal evaluation in follow-up.
AB  - OBJECTIVE: To analyze longitudinally the basal natural killer cell activity in
      patients with invasive cervical carcinoma, the natural cytotoxicity was related
      to the most important known prognostic factors, and evaluated with respect to the
      clinical outcome of cervical disease. MATERIALS AND METHODS: Forty-six patients
      with histologically proven invasive cervical carcinoma treated and followed at
      the Institute of Gynecology and Obstetrics, Ancona University, Salesi Hospital,
      were consecutively recruited from 1989 to 1992 and included into the study. For
      immunologic investigation, natural killer cell activity and peripheral blood T
      lymphocyte subsets were tested before primary treatment and during the follow-up
      period, every 6 months. Natural killer activity was determined by target cell
      retention of the fluorescent dye carboxyfluorescein diacetate; the K 562 cell
      line was used as target cells. RESULTS: A significant inverse relationship was
      observed between natural killer activity and disease stage (p = 0.001); patients
      with stage IV disease had the lowest level of natural cytotoxicity. The reduction
      of natural cytotoxicity was not accompanied by any alteration of lymphocyte
      distribution. The longitudinal analysis showed an increase of natural killer
      activity after surgical removal of the tumor, persisting during the follow-up,
      but all the 9 patients who recurred showed, at the time of disease recurrence, a
      significant decrease of their natural cytotoxic potential. CONCLUSION: Natural
      killer cell activity seems to be a functional index of immune status,
      significantly related to the stage and the clinical outcome of disease.

PMID- 8575693
TI  - Falsely elevated steroidal assay levels related to heterophile antibodies against
      various animal species.
AB  - Two cases of falsely elevated serum estradiol and 1 case of spuriously elevated
      serum progesterone performed on an automated immunoassay instrument are
      described. Further testing of same specimens indicated the presence of
      heterophilic antibodies against rabbit IgG and sheep IgG, respectively.

PMID- 8575694
TI  - Adult extrarenal Wilms' tumor. A case report.
AB  - Wilms' tumor or nephroblastoma is a malignant tumor of childhood and there are
      less than 200 cases in adults reported in the literature. An extrarenal location
      is also a rare situation for these tumors. A 48-year-old patient, referred to our
      gynecology department because of an abdominal mass, was operated on with a
      preoperative diagnosis of a possible ovarian tumor. The diagnosis of an
      extrarenal Wilms' tumor (ERWT) was made pathologically. Since it is a very rare
      entity, ERWT of adult origin is presented and the related literature is reviewed.

PMID- 8575695
TI  - The controversial role of cAMP on amnionic prostaglandin release: effect of
      adenylate cyclase inhibition.
AB  - The suggested role of cAMP in the regulation of amnionic prostaglandin release
      was investigated using two adenylate cyclase inhibitors, MDL 12330A and SQ 22536.
      These substances exhibited a dose-dependent inhibitory effect on both amnionic
      enzyme and cAMP levels, but they did not influence prostaglandin E (PGE) release.
      In addition forskolin and IBMX (3-isobutyl-1-methylxanthine), two drugs known to
      increase cAMP levels, did not affect PGE output, while dibutyryl cyclic cAMP
      showed a dose-dependent inhibitory effect. On the basis of our data, the
      suggested role of amnionic adenylate cyclase in triggering prostaglandin release
      is not confirmed, and the pathway of phospholipase A2 activation at the onset of
      labor remains to be elucidated.

PMID- 8575696
TI  - Flow velocity waveforms of the uterine artery in pregnancy: transvaginal versus
      transabdominal approach.
AB  - Our objective was to compare recordings of flow velocity waveforms from the
      uterine artery via the transvaginal and transabdominal approach in normal human
      pregnancies. In a cross-sectional study from 16 to 40 weeks' gestation, 88
      healthy pregnant women underwent a continuous-wave Doppler examination of their
      uterine arteries by both the transvaginal and the transabdominal approach.
      Measurements were recorded for both uterine arteries and averaged. Values
      recorded transabdominally were significantly lower than those obtained
      transvaginally in all patients < or = 27 weeks' gestation. From 28 weeks to term,
      transabdominal values remained lower, but the difference was smaller and
      insignificant, and noted only as a trend. Transvaginal velocimetry of the uterine
      artery produces significantly higher systolic:diastolic ratios than that of
      transabdominal recordings until 27 weeks' gestation. Thereafter, trophoblastic
      invasion of the uteroplacental circulation is maximal, and the difference between
      the values are minimal and insignificant. However, a pattern of lower resistance
      in the transabdominal approach remains consistent until term.

PMID- 8575697
TI  - A new formula for prenatal ultrasonographic weight estimation in extremely
      preterm fetuses.
AB  - A new formula for the prenatal estimation of the weight of extremely preterm
      fetuses was derived using ultrasound measurements and birth weights of 73
      premature infants delivered before 30 completed weeks of pregnancy and weighing
      between 400 and 1,680 g at birth. The actual birth weight lay within +/- 15% of
      the estimated weight calculated with this formula in 92% of the cases.
      Preliminary testing of the reliability of the formula was performed on a further
      test group of 19 nonselected cases. The formula developed in this study offers a
      reliable and simple method of prenatal estimation of fetal weight between 23 and
      30 weeks of gestation.

PMID- 8575698
TI  - Preinduction prostaglandin E2 gel prior to induction of labor in women with a
      previous cesarean section.
AB  - The objective of the study was to evaluate the efficacy and safety of
      preinduction cervical ripening with 0.5 mg of intracervical prostaglandin E2
      (PGE2) gel in women with a previous cesarean section. A retrospective cohort
      study design was used to compare 117 women with one previous cesarean section
      (VBACS) with 354 nulliparas. Both groups received preinduction cervical ripening
      treatment with intracervical PGE2 gel. Student's t and chi 2 tests were used to
      evaluate group differences. Mantel-Haenszel summary risk ratios and 95%
      confidence intervals were examined in order to assess the relative risk of
      cesarian section delivery after adjusting for potential confounders. The mean
      numbers of PGE2 gel applications were 2.4 and 2.5 for VBACS and controls,
      respectively (p < 0.05). Thirty-nine percent of VBACS entered labor spontaneously
      as compared with 33% of nulliparas. Mean duration of ruptured membranes (8.2 vs.
      12.1 h) and length of labor (20.1 vs. 28.5 h) were reduced among VBACS as
      compared with controls (p < 0.05). Overall, VBACS had a higher cesarean section
      rate as compared with controls (49.6 vs. 31.9%; adjusted relative risk = 1.6, 95%
      confidence interval 1.2-2.1). There were no differences in the occurrence of
      maternal and fetal morbidity. Overall, the efficacy and safety of 0.5 mg PGE2 gel
      administered for preinduction cervical ripening in VBACS is comparable to that
      observed in nulliparas.

PMID- 8575699
TI  - Invasive prenatal procedures: is 'backup' tissue sampling indicated?
AB  - Prenatal karyotyping was performed on 136 patients because of one or more
      abnormalities detected on ultrasound. A total of 188 specimens was obtained which
      included fetal blood, amniotic fluid and chorionic villus. In 52 patients a
      second or 'backup' sample was obtained and in 100% cytogenetic analysis was
      successful. In contrast, failure to obtain a result occurred in 4 (4.7%) of the
      remaining 84 patients where a second sample was not obtained. In the event of
      primary sample failure, backup sampling not only improves the karyotype yield,
      but obviates the need for a second pass procedure with its attendant risks.

PMID- 8575700
TI  - Stable engraftment of human female genital mucous membrane xenografts on SCID
      mice.
AB  - We developed a model in which full-thickness human genital mucous membranes
      (fallopian tubes, endometrium) were heterotopically xenografted into the skin of
      severe combined immunodeficient (SCID) mice. The transplanted tissue retained its
      human phenotype for at least 4 weeks including the glandular epithelium, the
      lamina propria, and main parts of the grafted vessels. By using an occlusive
      chamber filled with covering phosphate-buffered saline we created a system that
      protected the moist human epithelial surface. This system will allow the study of
      the interaction of test substances, or of invasive, pathogenic microorganisms,
      with epithelial cells and other cellular components of the human genital mucosa
      under in vivo conditions.

PMID- 8575701
TI  - [Sexual abstinence of thrombosis? Comment on the controversy regarding the "pill
      of the 3rd generation"].

PMID- 8575702
TI  - [The alcoholic patient in general practice. From initial contact to implementing
      therapy].
AB  - General practitioners play an important role in the treatment of alcoholism. It
      is their task to come in contact with patients to assess the severity of their
      alcohol-related problems and to encourage them to stop drinking. As a rule,
      detoxification can be completed in less than two weeks. Slight withdrawal
      symptoms do not require drug treatment. However, alcoholics with heavy long-term
      continuous drinking need in-patient withdrawal treatment. After detoxification,
      out-patient treatment conditions are sufficient for highly motivated patients
      living under stable social conditions. In German facilities, short-term therapies
      of 4-6 weeks are adapted to the less disabled, long-term therapies of 2-6 months
      to physically and mentally more disabled patients. In Germany, in-patient
      treatment in specialized clinics is paid for under the pension insurance scheme.
      The results of alcoholism treatment are better than generally expected. Four
      years after treatment in specialized units, up to 61% of patients are abstinent.

PMID- 8575703
TI  - [Role of the family physician in treatment of alcoholic patients].
AB  - In Western countries alcohol is a socially accepted drug and its use is on the
      increase. Accordingly, the number of alcoholics is also increasing. An important
      task of the general practitioner is first to recognize that a patient has a
      drinking problem, and then to help him/her to acknowledge and come to terms with
      the situation. Additionally he must motivate the patients to accept the need for
      suitable treatment and initiate it. Prevention of alcoholism, however, is not a
      matter of the medical profession alone, but is first and foremost a problem of
      our society. For a remedial approach to be effective, interdisciplinary
      cooperation between internists, psychologists, psychiatrists and social workers
      is a must, and here the general practitioner has a coordinating function to
      fulfill.

PMID- 8575704
TI  - [Alcohol drinking--problems in assessing the public economic impact].
AB  - Alcohol consumption is usually regarded as sizeable economic burden to society.
      Here it is argued that only the external costs of alcohol consumption represent
      the true costs to society. The methodological and empirical difficulties
      encountered in assessing these costs may explain the inadequacy of most of the
      empirical studies available. Therefore, at the moment a valid assessment of the
      economic burden of alcohol consumption in Germany is not feasible. Anyhow, such
      an assessment seems to be of questionable value because the actual situation is
      compared with a hypothetical non-alcohol situation. Therefore, economists should
      focus on cost-benefit-analysis of real-world policy options.

PMID- 8575705
TI  - [Dermatomycoses. 15: Isolation and differentiation of the main pathogenic skin
      fungi--fungal cultures].

PMID- 8575707
TI  - [Becoming aware of unaware body sensations. Psychotherapy series, 12: Functional
      relaxation].

PMID- 8575708
TI  - [World Health Report shows children as the sad losers. Almost 10 million AIDS
      orphans can be expected].

PMID- 8575706
TI  - [Acetylsalicylic acid as free radical scavenger. An argument for increased
      dosages in acute and preventive therapy of vascular diseases].

PMID- 8575709
TI  - [p53--a key gene for cancer development. Its central significance discloses
      itself to researchers step by step].

PMID- 8575710
TI  - [Constipation and intestinal flora--stimulation instead of irritation].

PMID- 8575711
TI  - [Synovectomy of the knee joint in rheumatoid arthritis. Follow-up studies].
AB  - A total of 156 synovectomies were performed to treat recurrent swelling of the
      knee joints in 148 patients with rheumatic diseases. The late results observed in
      112 patients (72%) re-examined after an average follow-up period of 6.2 years are
      discussed. The subjective and objective findings in patients undergoing early
      surgery proved to be superior to those seen after late synovectomy. Also in
      comparison with a group of patients submitted to synoviorthosis, surgical
      synovectomy, in particular when carried out at an early stage, showed more
      favorable results. For this reason, should conservative treatment fail, and
      recurrent swelling of the knee joints persist, early surgical intervention ist
      recommended.

PMID- 8575712
TI  - [Alcoholism as a social problem. The alcoholic patient in a permissive societies-
      possibilities for prevention].
AB  - While the permissive attitude of our society promotes the use of alcohol in a
      wide variety of ways, alcohol addiction is a social stigma. Addictive alcohol
      abuse often arises from an acquired habit of drinking to reduce conflict and
      tension. A social history may reveal the patient's weaknesses and his resources.
      It has been shown that alcoholics have inadequate capabilities (resources) for
      dealing with stressful situations. With respect to the prevention of alcohol
      misuse in our society, a new health awareness might help reduce an individual's
      "alcohol risk".

PMID- 8575713
TI  - [Dermatomycoses. 16: Topical therapy of skin and mucous membrane mycoses].

PMID- 8575714
TI  - [Regulation of antro-duodenal motility. Neural reflux mechanisms and action of
      neurotransmitters and neuropeptides].

PMID- 8575715
TI  - [6 weeks as a physician in a poverty shelter. Report of experiences in Cali,
      Columbia].

PMID- 8575716
TI  - [With interferon and zidovudine against therapy refractory T-cell leukemias].

PMID- 8575717
TI  - [Patchy changes in white matter in cranial computerized and magnetic resonance
      tomography--significance for (differential) diagnosis of dementia of the
      Alzheimer type and vascular dementia].
AB  - With the advancement of technical progress, especially with respect to magnetic
      resonance imaging, patchy cerebral white matter lesions (WML) are being found
      with increasing frequency. The (differential) diagnosis between the two main
      dementias of old age, (senile) dementia of the Alzheimer type ([S]DAT) and
      vascular dementia (VD) is made more frequently in favour of the latter, since the
      detection of WML leads to support a vascular origin for dementia. The present
      article reviews the literature concerning X-ray computed tomography (CT) and
      magnetic resonance imaging (MRI) in these disorders. For comparison purposes some
      methodological problems must be taken into account including different scoring
      systems for WML severity, differences in imaging techniques and in the criteria
      for the selection of patients and controls. A great number of studies
      demonstrates a strong association of frequency and severity of WML with
      increasing age and presence of cerebrovascular risk factors such arterial
      hypertension. Some studies revealed an association with neuropsychiatric deficits
      including gait disorders, urinary incontinence, affective lability and reduced
      attention and information processing speed. In CT studies, about 30% of patients
      with (S)DAT had WML but 36-88% in MR studies. However, only few studies
      controlled for the presence of cerebrovascular risk factors. More recent studies 
      with improved techniques - revealed a higher frequency of (slight or moderate)
      WML in the (S)DAT group compared to controls. The prevalence of WML in VD
      patients was 75-97% in CT studies and about 100% in MR studies. Therefore,
      without the presence of WML, the diagnosis of VD is currently in doubt. A number
      of in vivo investigations proved consistently - and with different methods - that
      cerebral blood flow was reduced in WML regions. As shown in some studies the
      neuropathologic correlates of WML have in common that the relative tissue water
      content is increased: This includes inflammation, gliosis, complete and
      incomplete infarctions, dilation of the perivascular (Virchow-Robin) spaces with
      myelin atrophy. Thus the finding of WML in watershed areas can be understood.
      Three case reports serve to illustrate the problems pointed out. In conclusion,
      the occurrence of WML is an unspecific finding which is observed in up to 50% of
      the elderly. Diagnostic classification as "vascular lesions" or signs of
      "vascular encephalopathy" or VD based on CT or MRI alone, should not be made.

PMID- 8575718
TI  - [Humoral aspects of sleep deprivation].
AB  - The effects of an antidepressant sleep deprivation on humoral systems and
      neurotransmitter systems are reviewed (cortisol, endorphins, thyroidea, growth
      hormone, prolactin, catecholamines, sexual hormones, melatonin, serotonin). The
      main results are: Depressed patients have a physiological response similar to
      controls with some differences between responders and nonresponders (responders
      are more similar to controls). TSH is more activated in responders than in
      nonresponders. The dopamine system is more activated in responders than in
      nonresponders and less activated in responders before sleep deprivation. The
      glucocorticoid-axis in more activated in responders after sleep deprivation. In
      conclusion, patients who profit from sleep deprivation can activate systems
      correlated with arousal or stress.

PMID- 8575719
TI  - [Panic disorder and agoraphobia: what is effective?].
AB  - The present survey of controlled studies on the treatment of panic disorder and
      agoraphobia (PDA) reveals that treatment with tricyclic antidepressants (e.g.,
      imipramine and clomipramine), benzodiazepines (e.g., alprazolam), serotonin
      reuptake inhibitors (e.g., fluvoxamine) and the monoamine oxidase inhibitor
      phenelzine has been proven effective. Among psychological therapies, cognitive
      therapy and exposure therapy in agoraphobia have been shown to be effective.
      There is an insufficient number of comparisons between pharmacological and
      psychological treatments. From the existing studies it can be assumed that none
      of these treatment modalities is superior to the other. The few existing follow
      up studies do not suffice to prove a longer lasting effect for the psychological
      therapies, compared with drug therapies. Because of the low number of
      investigations, it cannot be clearly stated whether it is useful or harmful do
      treat patients with psychopharmacological drugs during psychological therapy. It
      is more likely that this combination is advantageous.

PMID- 8575720
TI  - Effect of troglitazone, a new oral antidiabetic agent, on fructose-induced
      insulin resistance.
AB  - Troglitazone, a newly developed oral antidiabetic agent, improves hyperglycemia,
      and has been reported to improve insulin resistance and to decrease hepatic
      glucose production in diabetic animals. However, the exact mechanism of
      Troglitazone on the improvement of insulin resistance is not known. Chronic
      administration of fructose to normal rats leads to hyperglycemia, and
      hyperinsulinemia; it induces insulin resistance. To reveal the mechanism of
      Troglitazone, we studied the effect of Troglitazone on serum glucose and insulin
      in the fructose-induced, insulin-resistant rats. Male Sprague-Dawley (SD) rats
      were fed either on standard chow or one containing fructose. Troglitazone was
      administrated as a food admixture (150 mg/kg/day) for 8 weeks. The rats were fed
      on (1) standard chow, (2) standard chow and Troglitazone, (3) fructose-enriched
      chow, or (4) fructose-enriched chow and Troglitazone. Blood samples were obtained
      every two weeks, and the levels of serum glucose and insulin were measured.
      Fructose-enriched chow increased serum glucose and insulin levels and insulin-to
      glucose ratios. Troglitazone improved the fructose-induced increases in serum
      glucose, insulin levels, and insulin/glucose ratios. In conclusion, Troglitazone
      improved the fructose-induced insulin resistance.

PMID- 8575722
TI  - The human insulin-like growth factor-II promoter P1 is not restricted to liver:
      evidence for expression of P1 in other tissues and for a homologous promoter in
      baboon liver.
AB  - The human insulin-like growth factor (IGF)-II gene (IGF2) contains 4 different
      promoters (P1-P4), three of which (P2-P4) are homologous to the 3 promoters found
      in murine IGF-II genes. IGF-II is abundantly expressed in adult humans and
      primates, but IGF2 is only expressed in brain in adult rat and mouse. Previously,
      promoter P1 had been found exclusively in human adult liver but not in other
      human tissues or in rat or mouse liver. Although mouse liver does not express a
      homologue of human P1 mRNA, 5' "pseudo-exons" which are homologues of human exons
      2 and 3 have been identified in murine IGF2. Based on the published DNA sequences
      of human exon 2 and the homologous murine pseudo-exon psi 1, we designed a 5'
      oligonucleotide common to both human and murine IGF2 and a 3'-oligonucleotide
      primer from coding exon 7. We amplified specific cDNA from human and baboon
      livers, but no specific band was seen in rat or mouse liver. Chain-termination
      DNA sequencing confirmed that the P1 mRNA sequence from baboon liver shares 90%
      homology with human P1 mRNA in the 5' noncoding region (exons 2 and 3). Mature
      baboon IGF-II peptide is identical to human IGF-II, but there are 7 amino acid
      differences in the E region of the IGF-II prohormone. In humans, IGF-II mRNA
      transcripts containing P1 were also found in human myometrium and myomas. Our
      results demonstrate that the P1 promoter of the IGF-II gene is present in human
      and baboon adult liver, although it is absent from murine liver. In humans,
      promoter P1 is also utilized in tissues other than adult liver. We speculate that
      promoter P1 may be an important factor in persistent IGF-II synthesis.

PMID- 8575721
TI  - Effects of glucose and an aldose reductase inhibitor on albumin permeation
      through a layer of cultured bovine vascular endothelial cells.
AB  - The effects of high glucose concentrations on the selective permeability of a
      layer of cultured bovine vascular endothelial cells (ECs) were investigated. ECs
      were derived from the intima of the thoracic aorta and permeability to
      nonglycated albumin, glycated albumin, and fluorescein dextrans (FDs) of
      molecular mass to albumin was measured. ECs were cultured on a filter coated with
      type I collagen and preincubated in the presence of various glucose
      concentrations for 96 h. Human serum albumin was glycated by incubation with
      glucose in vitro. Nonglycated and glycated albumin were separated by affinity
      column chromatography. The permeation rates of nonglycated and glycated albumin
      as well as those of neutral and anionic FD through the EC layer were increased by
      preincubation of cells with high glucose concentrations (22.2 and 44.4 mmol/l).
      The permeation rate of glycated albumin was significantly less than that of
      nonglycated albumin at all glucose concentrations tested, whereas the permeation
      rate of anionic FD was significantly lower than that of neutral FD only at a
      physiological glucose concentration (5.6 mmol/l). The aldose reductase inhibitor
      ponalrestat partially inhibited the high glucose-induced increase in trans
      endothelial permeation of albumin (both nonglycated and glycated), but had no
      effect on the increased permeation of FD. These results indicate that high
      glucose concentrations enhance trans-endothelial permeability to albumin and FD
      and may disturb the barrier function of vascular ECs. Furthermore, metabolism of
      glucose via the polyol pathway may contribute to abnormalities in trans
      endothelial permeability.

PMID- 8575723
TI  - Iodine metabolism in response to goitrogen induced altered thyroid status under
      conditions of moderate and high intake of iodine.
AB  - Metabolic experiments in rats were undertaken to relate excretory pattern of
      iodine and thiocyanate, with thyroid weight and the circulating levels of
      thyroxine, in response to moderate and high intake of iodine and under conditions
      of goitrogen induced altered thyroid status. On a moderate intake of iodine (by
      depriving diet of KI) 25 mg of thiocyanate or substitution of 1/3rd proportion of
      casein based diet with dry cabbage, could significantly reduce plasma thyroxine
      level by 60 days. Neither body weight nor the weights of liver, kidney, heart or
      spleen were affected due to exposure to goitrogens. A significant increase in
      thyroid weight as well as higher excretion of iodine and thiocyanate were evident
      in goitrogen-fed rats. Presence of high amounts of KI, to a certain extent,
      offered protection from adverse effects of the goitrogens. Semi quantitative
      assessment of thyroid, indicated hypofunctioning of thyroid with follicular
      hyperplasia in thiocyanate fed rats. These alterations were of moderate degree in
      response to cabbage feeding. These results emphasize that, moderate intake of
      iodine, adequate to meet iodine requirement, may not ensure normal functioning of
      thyroid in the presence of goitrogens.

PMID- 8575724
TI  - Effect of 1,10-phenanthroline on DNA binding by 1,25-(OH)2 vitamin D receptor.
AB  - The effect of the chelator 1,10-phenanthroline on the DNA-binding of 1,25
      dihydroxyvitamin D receptor was demonstrated. Increasing concentrations of the
      chelator, up to 3 mM, decreased receptor binding to DNA-cellulose. This effect
      was specific for the chelating function because the nonchelating analog, 1,7
      phenanthroline, did not inhibit DNA-cellulose binding of the receptor. The
      cations Cd2+ and Zn2+ were able to block chelator-mediated inhibition. These
      cations were unable to reverse the inhibition unless 1,10-phenanthroline was
      removed by dialysis.

PMID- 8575725
TI  - 1,25-Dihydroxyvitamin D synthesis in rat liver microsomes.
AB  - Previous studies from our laboratory have shown 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] production by rat liver homogenates and a low affinity of the
      hepatic enzyme for 25-hydroxyvitamin D3. Because the liver microsomal vitamin D
      25-hydroxylase is the main source of systemic 25(OH)D3, we examined the
      subcellular location and the kinetics of liver 1,25(OH)2D3 production. Unlike the
      renal 1 alpha-hydroxylase activity which was assayed simultaneously, 1,25(OH)2D3
      synthesis was undetectable in rat liver mitochondria, whereas in microsomes,
      1,25(OH)2D3 production followed typical Michaelis Menten kinetics with a Km for
      25(OH)D3 of 13.4 microM and a Vmax of 109.8 pg/min per mg protein accounting for
      most of the 1,25(OH)2D3 synthesized by rat liver cytosol free homogenates. Thus,
      microsomes are the site for 1,25(OH)2D3 synthesis in the rat liver. This
      microsomal compartmentalization of the two major steps in the activation of
      vitamin D to 1,25(OH)2D3 suggests a role for the liver as an autocrine/paracrine
      organ for 1,25(OH)2D3.

PMID- 8575726
TI  - The role of thymosin F5 on anemia in hypercholesterolemic rabbits.
AB  - New Zealand White rabbits were made hypercholesterolemic by feeding a high
      cholesterol diet (20 g/kg diet) for 3 months. Plasma cholesterol concentrations
      were monitored as a function of time. At the end of 3 months, the plasma lipid
      levels, the whole blood, erythrocyte and haemoglobin-bound 2,3-DPG levels and
      leucocyte counts increased, whereas erythrocyte counts, hematocrit and
      haemoglobin levels decreased significantly in hypercholesterolemic rabbits. At
      the end of 3 months, the rabbits in the experimental group were divided into two
      groups. The first group was fed a standard diet for 21 days. The second group
      received 0.5 mg/kg thymosin F5 injection i.p. every other day for 21 days. After
      this period, the plasma lipid levels, the whole blood, erythrocyte and
      haemoglobin-bound 2,3-DPG levels, erythrocyte and leucocyte counts, hematocrit
      and haemoglobin levels were measured. Rabbits fed diets supplemented with
      thymosin F5 had markedly lower plasma lipid levels, erythrocyte counts,
      hematocrit and haemoglobin levels and enhanced leucocyte counts, but did not have
      significantly less whole blood, erythrocyte and haemoglobin-bound 2,3-DPG levels.
      We conclude that thymosin F5 has lipid-lowering effects in hypercholesterolemic
      rabbits. The data further suggest that effects of thymosin F5 on haematological
      parameters are due to the cholesterol decrease and not to the direct regulatory
      mechanism.

PMID- 8575728
TI  - Calcitonin gene-related peptide during exercise and training.

PMID- 8575727
TI  - Metabolic abnormalities following heart transplantation in patients with
      idiopathic cardiomyopathy.
AB  - The purpose of this study was to evaluate the risk factors for coronary artery
      disease associated with initiation of immunosuppressive therapy in patients with
      a pre-heart transplant diagnosis of idiopathic cardiomyopathy. This study was
      performed in 15 consecutive patients, mean +/- SEM age of 39 +/- 2 years, with a
      pre-operative diagnosis of idiopathic cardiomyopathy, who underwent cardiac
      transplantation at the Tri-Services General Hospital, Taipei, Taiwan, from July
      1992 to June 1993. All patients were treated with cyclosporine, azathioprine and
      prednisolone, and the following measurements were performed prior to hospital
      discharge (mean +/- SEM) 36 +/- 3 days after successful transplantation: 1)
      fasting plasma lipid and lipoprotein concentrations; 2) plasma glucose and
      insulin concentrations in response to a 75 g oral glucose challenge; and 3)
      steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response
      to a continuous infusion of somatostatin, insulin, and glucose. Since the SSPI
      concentrations are similar in all individuals, the SSPG concentrations provide an
      estimate of the ability of insulin to stimulate glucose disposal. Only six of the
      patients had a normal oral glucose tolerance test and the following diagnoses
      were found in the remaining nine patients: not diagnised (n = 3), impaired
      glucose tolerance (n = 4), and non-insulin-dependent diabetes (n = 2). Plasma
      lipid and lipoprotein concentrations were also frequently abnormal in the heart
      transplant patients; eight of the 15 patients had a plasma cholesterol > 5
      mmol/l, nine had a high density lipoprotein (HDL)-cholesterol concentration < 1
      mmol/l, and nine had a ratio of total to HDL-cholesterol > 5.0. Finally, the SSPG
      concentration was greater than 11.0 mmol/l in eight of the 15 patients, a value
      rarely exceeded in healthy volunteers. In conclusion, significant metabolic
      abnormalities were present at discharge in patients who had undergone successful
      cardiac transplantation for idiopathic cardiomyopathy. These metabolic
      abnormalities were probably caused by the use of immunosuppressive drugs. Given
      the magnitude of these changes, it would seem prudent to initiate therapeutic
      programs in patients with cardiac transplants that are not simply aimed at
      preventing rejection, but also address the metabolic abnormalities associated
      with the immunosuppressive agents used to prolong allograft survival.

PMID- 8575729
TI  - Assessment of cell proliferation in normal and pathological bone marrow biopsies:
      a study using double sequential immunophenotyping on paraffin sections.
AB  - The proliferative activity of the haematopoietic and plasma cells in bone marrow
      was evaluated under normal and neoplastic conditions, by means of a sequential
      double immunostaining technique, using monoclonal antibody MIB-1 recognizing the
      cell proliferation-associated nuclear antigen Ki-67, and antibodies against
      glycophorin-C, myeloperoxidase, factor VIII-related antigen, and immunoglobulin
      light chains. Fifty-eight B5 fixed, paraffin-embedded bone marrow biopsies were
      analysed, including 11 normal controls. 10 cases of myelodysplasia, 14 cases of
      chronic myeloproliferative disorder, eight cases of acute non-lymphoid leukaemia,
      and 15 cases of myeloma. In normal marrows, the highest proliferative activity
      was noticed in the erythroid cells (75% to 95%; mean 90%), in comparison with
      myeloid precursors (15% to 80%; mean 38%), and megakaryocytes (10% to 20%; mean
      14%): no Ki-67 positive plasma cells were found. In all investigated
      haematological disorders, the expression of MIB-1 by erythroid cells was similar
      to that observed in controls. Similarly, the percentage of MIB-1 + myeloid
      precursors in chronic myeloproliferative disorders and myelodysplasia largely
      overlapped the values observed in normals, and comparable values were also found
      in the blast cells from acute non-lymphoid leukaemia type M1 and M2. These
      findings suggest that the evaluation of either erythroid or myeloid proliferative
      activity is of little value in the differential diagnosis between these
      myeloproliferative disorders. By contrast, the obvious increase of Ki-67
      expression of megakaryocytes in chronic myeloproliferative disorders, with
      labelling also of micro-megakaryocytes, might sustain the diagnosis in
      controversial cases. Since cases of mature myeloma showed less than 2% of Ki-67
      positive cells, evaluation of proliferative activity is of no value in the
      differential diagnosis with reactive plasmacytosis. The sequential double
      immunophenotyping for Ki-67 antigen and for haematopoietic cell lineage
      associated markers can be applied in a consistent manner to routine bone marrow
      biopsies to evaluate proliferating cells in normal and neoplastic conditions.

PMID- 8575731
TI  - Comparison of ploidy analysis by flow cytometry and image analysis in
      hydatidiform mole and non-molar abortion.
AB  - Determination of DNA ploidy is useful in the diagnosis and classification of
      hydatidiform mole. Most reports of ploidy analysis in molar tissue have used DNA
      flow cytometry. Although image analysis cytometry offers theoretical advantages
      over flow cytometry, there have been few reports of ploidy analysis by image
      analysis in hydatidiform mole. We selected 47 cases and measured DNA ploidy by
      flow cytometry and image analysis cytometry in complete hydatidiform mole,
      partial hydatidiform mole and non-molar abortion. The two cytometry modalities
      were compared using kappa statistics. There was reasonable overall agreement
      between the two modalities (kappa = 0.69) and when ploidy was stratified into
      diploid/polyploid and triploid categories there was near perfect agreement (kappa
      = 0.93). Aneuploid cell populations, which were not evident on flow cytometry,
      were identified by image analysis in a significant proportion of complete and
      partial hydatidiform moles and in a small number of non-molar abortions. Flow
      cytometry and image analysis cytometry yield comparable ploidy information,
      useful in the diagnosis and classification of hydatidiform mole. Image analysis
      cytometry offers greater sensitivity in the detection of small non-diploid cell
      populations but the significance of this latter finding is uncertain.

PMID- 8575730
TI  - Antibodies to cytokeratins bind to epitopes in human uterine smooth muscle cells
      in normal and pathological pregnancies.
AB  - Cytokeratin antibodies have been widely used for the identification of
      trophoblast cells in the placental bed, following their invasion from the
      developing conceptus. Their identification centres upon the expression of
      cytokeratin in epithelial cells, from which trophoblast cells are derived. Our
      recent observations indicate that this strict relationship may be more complex
      than was thought. Cryostat and paraffin sections of human decidua and myometrium,
      taken from the placental bed and the uterotomy cut, were examined
      immunocytochemically for cytokeratins using ten antibody clones selected to
      identify different cytokeratin proteins and antigenic epitopes. Biopsy specimens
      were obtained from normal and pathological pregnancies (pre-eclampsia, fetal
      retardation, amnioninfection, hysterorrhexis, placenta praevia) at the time of
      caesarean section (26-41 weeks of pregnancy). Antibodies against nine clones, CAM
      5.2, MNF 116, AE1/AE3, CK5, KS-B17.2, CY-90, M20, E3, and 34 beta E12 identified,
      as expected, syncytial giant cells and mononuclear trophoblasts within the
      placental bed and glandular epithelial cells throughout the uterus. In addition,
      they stained numerous fusiform cells that were classified by established criteria
      to represent smooth muscle cells, both within blood vessels and myometrium. No
      staining differences were observed between normal and pathological disorders.
      These results indicate that cytokeratin antibodies CAM 5.2, MNF 116 and AE1/AE3,
      and other antibodies targeting proteins 8 and 18, cross-react with epitopes
      expressed in cells other than giant trophoblastic cells and mononuclear
      trophoblasts in the uterus and, thus, caution has to be used when such antibodies
      are used for the diagnostic characterization of tissues related to the placental
      bed.

PMID- 8575732
TI  - Calcium oxalate crystal deposition in epithelioid histiocytes of granulomatous
      lymphadenitis: analysis by light and electronmicroscopy.
AB  - In this study of 55 cases of granulomatous lymphadenitis of various aetiologies,
      both haematoxylin and eosin stained and unstained sections were examined by light
      and polarizing light microscopy for crystals within epithelioid histiocytes. This
      investigation was prompted by a case of granulomatous lymphadenitis in which the
      identification of ovoid birefringent structures within epithelioid histiocytes
      led to an initial false suggestion of foreign body reaction. Identical single,
      small, ovoid or biconvex, intensely birefringent crystals, invisible by ordinary
      light microscopy, were found within the cytoplasm of mononuclear epithelioid
      histiocytes in 37 cases. There was only minor crystal loss with routine H & E
      staining. The sections were also examined by scanning electronmicroscopy in
      secondary and backscattered electron imaging modes and 27 cases were found to
      contain biconvex crystals which were shown on X-ray energy dispersive
      spectroscopic microanalysis to be consistent with calcium oxalate. There was a
      good quantitative correlation between light and scanning electron microscopy.
      Tissue from the index case was also examined by transmission electronmicroscopy,
      and electron dense crystals were identified. We confirm the previous findings of
      ovoid oxalate crystals in a variety of granulomatous conditions including
      Mycobacterial infection, sarcoidosis and Crohn's disease. Ovoid crystals of
      calcium oxalate, a common finding in granulomatous lymphadenitis, appear to be
      endogenously derived, and should be more widely recognized in order to avoid
      misdiagnosis of foreign body reaction.

PMID- 8575733
TI  - Histological study of oxalosis in the eye and adnexa of AIDS patients.
AB  - Review of a series of 98 eyes removed at autopsy from 86 AIDS patients identified
      12 cases (14%) showing varying degrees of microscopic calcium oxalate deposition.
      The oxalate crystals were birefringent using polarisation microscopy and were
      stained histochemically by the silver nitrate-rubeanic acid method (Yasue), a
      stain considered to be specific for calcium oxalate. In two cases, the deposition
      was extensive and involved the surface of the ciliary processes, ciliary body and
      pars plana of the retina, the retinal and optic nerve blood vessel wall, a few
      retinal pigment cells, and the anterior inner sclera. A lesser degree of
      intraocular involvement was observed in the remaining 10 cases. In all but two
      eyes, where a peripheral active area of cytomegalovirus retinitis was present, no
      other significant microscopical abnormality was found. Clinically, these patients
      were asymptomatic. At autopsy, oxalate deposits were found in the kidney and/or
      thyroid in seven of the patients.

PMID- 8575734
TI  - Arterial lesions associated with medial disorganization and fibrosis in
      endomyocardial biopsies from human cardiac allografts.
AB  - We describe distinctive arterial lesions in endomyocardial biopsies from patients
      with human cardiac allografts. The lesions affected principally the media of
      small arteries and consisted of misorientation of smooth muscle cells and
      fibrosis. This remodelling was most prevalent in the subadventitial zone, but
      sometimes extended to involve the full thickness of the media. In the most
      extreme cases medial smooth muscle cells ran parallel to the long axis of the
      vessel and were segregated into small bundles and single cells separated by
      collagen which merged with the adventitial fibrosis. The intima was always
      normal. Abnormal arteries were present in 16% of 603 consecutive biopsies from 44
      patients, and 39% of lesions occurred in 16% of patients. No lesions were found
      in endomyocardial biopsies from 25 non-transplanted patients, nor in mucosal
      biopsies from both transplanted and non-transplanted patients, confirming that
      the appearances were not due to biopsy artefact. There was early arterial
      remodelling in biopsies within two weeks of transplantation and none of the
      stages resembled vascular rejection. Fifty per cent of biopsies from some
      patients contained arterial lesions, suggesting that in susceptible patients they
      are common.

PMID- 8575735
TI  - Recurrent thymoma: evidence for histological progression.
AB  - The clinicopathological features of nine cases of recurrent thymomas have been
      studied. At presentation, all cases were histologically classified as thymomas
      with cortical differentiation, including predominantly cortical thymoma, cortical
      thymoma and well-differentiated thymic carcinoma. In five cases the morphological
      features of the recurrence(s) were suggestive of a histological progression of
      the tumour from predominantly cortical thymoma to cortical thymoma and/or well
      differentiated thymic carcinoma, usually associated with a more advanced clinical
      stage, the latter indicating a clinical progression. These findings suggest that
      all types of thymoma with cortical differentiation are histologically and
      histogenetically related neoplasms, associated with a more aggressive clinical
      behaviour and a significant risk of recurrence. The overall outcome of patients
      with recurrent thymoma in this series was poor, since six patients (66.6%) died
      due to the disease, 2-14 years after the first diagnosis. The clinical
      implication of our findings is that thymomas with cortical differentiation always
      need careful follow-up, even in those cases which are not obviously invasive at
      onset.

PMID- 8575736
TI  - DNA flow cytometric and immunohistochemical analysis of proliferative activity in
      spindle cell haemangioendothelioma.
AB  - Although spindle cell haemangioendothelioma was initially described as a low
      grade angiosarcoma, recent reports have suggested that it is a reactive or benign
      vascular proliferation. In order to assess the proliferative activity in spindle
      cell haemangioendothelioma, 12 cases, one of which was associated with Maffucci's
      syndrome, were immunohistochemically analysed with antibodies against
      proliferating cell nuclear antigen (PCNA), Ki-67 and p53. DNA flow cytometry was
      performed on six of the 12 cases. Seven of the 12 patients had multiple nodules
      or papules. Although two cases recurred once and twice, respectively, after
      surgery, there was no evidence of metastasis. Immunohistochemically, the
      percentages of PCNA, Ki-67 and p53 positive tumour cells ranged from 0.1% to 6.4%
      (mean 3.3%), 0.1% to 14.9% (3.5%) and 0.1% to 2.8% (1.1%), respectively,
      indicating a low proliferative activity and a low p53 expression in this tumour.
      All seven lesions from the six cases examined flow cytometrically were DNA
      diploid with proliferative indices (S + G2/M-phase fractions) ranging from 4.9%
      to 19.5% (mean, 10.9%). These findings are compatible with a bland-looking
      histological picture and an indolent clinical course of spindle cell
      haemangioendothelioma.

PMID- 8575737
TI  - Rheumatic Aschoff nodules revisited: an immunohistological reappraisal of the
      cellular component.
AB  - Rheumatic fever is still the leading cause of acquired heart disease in children
      and young adults in developing countries. Recent reports have documented a rising
      incidence of rheumatic fever in both the USA and Europe. The disease is
      characterized by specific lesions in the heart muscle and valves called Aschoff
      nodules. The Aschoff nodule has been neglected in the last few decades as most of
      the studies were conducted in the 1960s on autopsy tissues. This study examines
      Aschoff nodules using heart valve material obtained at valve surgery with updated
      commercially available immunohistochemical antibodies to determine the phenotypic
      characteristics of the cells involved in the formation of these lesions. Fifteen
      cases of rheumatic valvulitis, as indicated by the presence of Aschoff nodules,
      were examined. The Anitschkow and Aschoff cells stained prominently with
      macrophage markers. Three stages of nodules with Aschoff and Anitschkow cells
      were identified: stage 1, central fibrinoid necrosis without lymphocytes, stage 2
      with occasional T lymphocytes (< 10) and stage 3 with lymphoid aggregates
      containing both T- and B-lymphocytes (with occasional admixed macrophages). We
      propose that the stage 1 lesion is the earliest granulomatous stage with the
      lymphoid aggregates being a later stage in the development of Aschoff nodules.
      The Aschoff and Anitschkow cells demonstrated mitotic activity and stained with
      antibodies to the proliferation cell nuclear antigen (PCNA) suggesting that the
      multinucleated giant cells may be formed, at least partially, by nuclear division
      rather than fusion.

PMID- 8575738
TI  - Strumal carcinoid of the ovary associated with hyperinsulinaemic hypoglycaemia
      and cutaneous melanosis.
AB  - Using immunohistochemical techniques ovarian carcinoid tumours can be shown to
      contain a wide variety of neuro-hormonal peptides but clinical effects, apart
      from the carcinoid syndrome, are very rare. Non-islet cell tumours with
      documented hyperinsulinaemic hypoglycaemia are also rare. This is the first
      recorded case of an ovarian strumal carcinoid associated with hyperinsulinaemic
      hypoglycaemia. Concurrent skin hyperpigmentation is believed to have resulted
      from the effects of tumour derived alpha-melanocyte stimulating hormone or an
      antigenically similar, biologically active peptide.

PMID- 8575739
TI  - Association between the apoptotic index and established prognostic parameters in
      endometrial adenocarcinoma.
AB  - The aim of this study was to determine if the apoptotic index can be readily
      determined for endometrial carcinoma in hysterectomy specimens and to establish
      if any association exists between the apoptotic index and tumour grade and stage.
      The apoptotic index, defined as the percentage of morphologically identified
      apoptotic cells and apoptotic bodies in 3000 tumour cells, was calculated for 15
      adenocarcinomas of the endometrium. An association between apoptotic index and
      tumour grade and stage was sought. Two grade 3 adenocarcinomas of endometrium had
      a higher apoptotic index (5.15% to 6.43%) than 13 grade 1 and 2 lesions (1.18% to
      3.8%) and formed a distinct group in this series. No association between
      apoptotic index and tumour stage was demonstrable. Apoptotic index can be readily
      estimated in routine hysterectomy specimens for endometrial adenocarcinoma. A
      high apoptotic index shows an association with features normally correlated with
      a poor clinical outcome although its value as an independent prognostic index has
      yet to be established.

PMID- 8575740
TI  - Choriocarcinoma in situ: a case at an early gestational stage.
AB  - A case of choriocarcinoma in situ arising in an 11 week gestational placenta is
      reported. Histologically, a localized nodule, measuring 5 mm, of neoplastic
      trophoblastic proliferation appeared to arise directly from normal stem villi and
      projected into the intervillous space. The tumour was composed of biphasic
      cytotrophoblast and syncytiotrophoblast. No fetal elements were observed. The
      patient had a normal full-term spontaneous vaginal delivery 22 months after
      curettage and was free of disease without therapy at 32 months. This tumour
      provides evidence for an origin of choriocarcinoma from villous trophoblast. Our
      report illustrates the need to perform thorough microscopic examination of the
      products of conception, especially in the absence of a fetus or fetal parts.

PMID- 8575741
TI  - Multicentric intranodal myofibroblastoma in an infant.

PMID- 8575742
TI  - Multicystic mesothelioma of the spermatic cord.

PMID- 8575743
TI  - Solitary lymphangioma of the lung.

PMID- 8575744
TI  - Carcinosarcoma of lung associated with asbestosis.

PMID- 8575745
TI  - Human nicotinamide N-methyltransferase gene: molecular cloning, structural
      characterization and chromosomal localization.
AB  - Genomic DNA clones for nicotinamide N-methyltransferase (NNMT), an enzyme that
      catalyzes drug and xenobiotic metabolism, were isolated from a human chromosome
      11-specific DNA library. Study of one of those clones, when combined with PCR
      based experiments performed with human genomic DNA, made it possible to determine
      the structure of the human NNMT gene. The gene was approximately 16.5 kb in
      length and consisted of 3 exons and 2 introns. Transcription initiation for the
      NNMT gene occurred 105-109 nucleotides 5'-upstream from the cDNA translation
      initiation codon on the basis of the results of both primer extension and 5'
      rapid amplification of cDNA ends. NNMT mapped to chromosome band 11q23.1 by
      fluorescence in situ hybridization.

PMID- 8575746
TI  - The human myosin light chain kinase (MLCK) from hippocampus: cloning, sequencing,
      expression, and localization to 3qcen-q21.
AB  - Myosin light chain kinase (MLCK), a key enzyme in muscle contraction, has been
      shown by immunohistology to be present in neurons and glia. We describe here the
      cloning of the cDNA for human MLCK from hippocampus, encoding a protein sequence
      95% similar to smooth muscle MLCKs but less than 60% similar to skeletal muscle
      MLCKs. The cDNA clone detected two RNA transcripts in human frontal and
      entorhinal cortex, in hippocampus, and in jejunum, one corresponding to MLCK and
      the other probably to telokin, the carboxy-terminal 154 codons of MLCK expressed
      as an independent protein in smooth muscle. Levels of expression were lower in
      brain compared to smooth muscle. We show that within the protein sequence, a
      motif of 28 or 24 residues is repeated five times, the second repeat ending with
      the putative methionine start codon. These repeats overlap with a second
      previously reported module of 12 residues repeated five times in the human
      sequence. In addition, the acidic C-terminus of all MLCKs from both brain and
      smooth muscle resembles the C-terminus of tubulins. The chromosomal localization
      of the gene for human MLCK is shown to be at 3qcen-q21, as determined by PCR and
      Southern blotting using two somatic cell hybrid panels.

PMID- 8575747
TI  - Parsimonious estimation of sex-specific map distances by stepwise maximum
      likelihood regression.
AB  - In human genetic maps, differences between female (xf) and male (xm) map
      distances may be characterized by the ratio, R = xf/xm, or the relative
      difference, Q = (xf - xm)/(xf + xm) = (R - 1)/(R + 1). For a map of genetic
      markers spread along a chromosome, Q(d) may be viewed as a graph of Q versus the
      midpoints, d, of the map intervals. To estimate male and female map distances for
      each interval, a novel method is proposed to evaluate the most parsimonious trend
      of Q(d) along the chromosome, where Q(d) is expressed as a polynomial in d.
      Stepwise maximum likelihood polynomial regression of Q is described. The
      procedure has been implemented in a FORTRAN program package, TREND, and is
      applied to data on chromosome 18.

PMID- 8575748
TI  - Isolation of the mouse homologue of BRCA1 and genetic mapping to mouse chromosome
      11.
AB  - The BRCA1 gene is in large part responsible for hereditary human breast and
      ovarian cancer. Here we report the isolation of the murine Brca1 homologue cDNA
      clones. In addition, we identified genomic P1 clones that contain most, if not
      all, of the mouse Brca1 locus. DNA sequence analysis revealed that the mouse and
      human coding regions are 75% identical at the nucleotide level while the
      predicted amino acid identity is only 58%. A DNA sequence variant in the Brca1
      locus was identified and used to map this gene on a (Mus m. musculus Czech II x
      C57BL/KsJ)F1 x C57BL/KsJ intersubspecific backcross to distal mouse chromosome
      11. The mapping of this gene to a region highly syntenic with human chromosome
      17, coupled with Southern and Northern analyses, confirms that we isolated the
      murine Brca1 homologue rather than a related RING finger gene. The isolation of
      the mouse Brca1 homologue will facilitate the creation of mouse models for
      germline BRCA1 defects.

PMID- 8575749
TI  - Mucopolysaccharidosis type VI in rats: isolation of cDNAs encoding arylsulfatase
      B, chromosomal localization of the gene, and identification of the mutation.
AB  - Mucopolysaccharidosis (MPS) type VI, the lysosomal storage disorder caused by the
      deficiency of arylsulfatase B (ARSB) activity, occurs in humans, cats, and rats.
      To characterize the molecular lesion(s) causing MPS VI in rats, cDNAs encoding
      rat ARSB were isolated from a rat liver cDNA library. The nucleotide and deduced
      amino acid sequences of rat ARSB had approximately 80 and 85% identity with the
      human ARSB sequences, respectively. The chromosomal location of the rat ARSB gene
      was determined by PCR analysis of rat-mouse somatic cell hybrid panel. The ARSB
      gene was assigned to rat chromosome 2, where the locus for the MPS VI phenotype
      in rats has been localized by linkage analysis. To identify the mutation(s)
      within the ARSB gene causing MPS VI in rats, the ARSB sequence were amplified
      from affected animals and completely sequenced. Notably, a homoallelic one-base
      insertion at nucleotide 507 (507insC) was identified, resulting in a frame shift
      mutation and premature termination at codon 258. The presence of the insertion
      completely correlated with the occurrence of the MPS VI phenotype among 66
      members of the MPR rat colony. Thus, we conclude that 507insC is the causative
      mutation in these animals and that the MPS VI rats are an authentic model of
      human MPS VI.

PMID- 8575750
TI  - Complete structural organization of the human alpha 1 (V) collagen gene (COL5A1):
      divergence from the conserved organization of other characterized fibrillar
      collagen genes.
AB  - Genes that encode the vertebrate fibrillar collagen types I-III have previously
      been shown to share a highly conserved intron/exon organization, thought to
      reflect common ancestry and evolutionary pressures at the protein level. We
      report here the complete intron/exon organization of COL5A1, the human gene that
      encodes the alpha 1 chain of fibrillar collagen type V. The structure of COL5A1
      is shown to be considerably diverged from the conserved structure of the genes
      for fibrillar collagen types I-III. COL5A1 has 66 exons, which is greater than
      the number of exons found in the genes for collagen types I-III. The increased
      number of exons is partly due to the increased size of the pro-alpha 1(V) N
      propeptide, relative to the sizes of the N-propeptides of the types I-III
      procollagen molecules. In addition, however, the increased number of exons is due
      to differences in the intron/exon organization of the triple-helix coding region
      of COL5A1 compared to the organization of the triple-helix coding regions of the
      genes for collagen types I-III. Of particular interest is the increase of 54 bp
      exons in this region of COL5A1, strongly supporting the proposal that the triple
      helix coding regions of fibrillar collagen genes evolved from duplication of a 54
      bp primordial genetic element. Moreover, comparison of the structure of COL5A1 to
      the highly conserved structure of the genes of collagen types I-III provides
      insights into the probable structure of the ancestral gene that gave rise to what
      appears to be two classes of vertebrate fibrillar collagen genes.

PMID- 8575751
TI  - Cloning and characterization of CLCN5, the human kidney chloride channel gene
      implicated in Dent disease (an X-linked hereditary nephrolithiasis).
AB  - Dent disease, an X-linked familial renal tubular disorder, is a form of Fanconi
      syndrome associated with proteinuria, hypercalciuria, nephrocalcinosis, kidney
      stones, and eventual renal failure. We have previously used positional cloning to
      identify the 3' part of a novel kidney-specific gene (initially termed hClC-K2,
      but now referred to as CLCN5), which is deleted in patients from one pedigree
      segregating Dent disease. Mutations that disrupt this gene have been identified
      in other patients with this disorder. Here we describe the isolation and
      characterization of the complete open reading frame of the human CLCN5 gene,
      which is predicted to encode a protein of 746 amino acids, with significant
      homology to all known members of the ClC family of voltage-gated chloride
      channels. CLCN5 belongs to a distinct branch of this family, which also includes
      the recently identified genes CLCN3 and CLCN4. We have shown that the coding
      region of CLCN5 is organized into 12 exons, spanning 25-30 kb of genomic DNA, and
      have determined the sequence of each exon-intron boundary. The elucidation of the
      coding sequence and exon-intron organization of CLCN5 will both expedite the
      evaluation of structure/function relationships of these ion channels and
      facilitate the screening of other patients with renal tubular dysfunction for
      mutations at this locus.

PMID- 8575752
TI  - Determination and regional assignment of grouped sets of microclones in
      chromosome 1pter-p35.
AB  - In an approach to mapping physically the most distal 30 Mb of human chromosome
      1p, region-specific clone libraries were generated by microdissection and
      microcloning. PFGE blot hybridization of single or low-copy microclones against
      rare-cutter digests of genomic DNA revealed physical linkage for groups of
      markers. Supplementary PFGE analysis of 31 1p36-p35-specific probes for
      genetically mapped loci established a total of 15 grouped sets, consisting of
      altogether 69 markers. Twelve of the grouped sets were located in 1pter-p36.12,
      as revealed by microcell hybrid mapping; the remaining three were localized
      proximal to 1p36.12. Regional assignment and ordering of most grouped sets was
      achieved either by evaluating the included genetic markers or by fluorescence in
      situ hybridization of representative probes. The genomic extent of individual
      grouped sets encompassed between 1100 and 2100 kb, covering a total of
      approximately 22 Mb of the distal chromosome 1p region. One particular grouped
      set was shown to contain seven polymorphic marker loci that were previously
      suggested to be distributed across the entire 1pter-p35 region. The increase in
      the number of hybridization marker probes in 1p36 and their physical mapping is
      expected to facilitate positional cloning experiments in this region; in
      particular, the construction of clone contigs may be greatly facilitated.

PMID- 8575753
TI  - Isolation of murine telomere-proximal sequences by affinity capture and PCR.
AB  - We describe a method of selectively enriching for murine telomere-proximal
      sequences using affinity capture followed by PCR amplification. The telomeric
      fragments were selected from NotI-digested and lambda exonuclease-resected mouse
      genomic DNA by annealing to a biotinylated riboprobe containing multiple copies
      of the telomere repeat (TTAGGG)n. The resultant DNA-RNA hybrids were selectively
      retained on a matrix with covalently bound avidin. The captured DNA was then
      specifically released by ribonuclease action, and PCR amplification was performed
      using mouse repeat primers. The PCR products were cloned and used to screen a
      mouse genomic cosmid library, and the resultant cosmid clones were analyzed by
      fluorescence in situ hybridization. Ten of 70 clones analyzed gave telomere
      proximal hybridization signals, indicating an at least 500-fold enrichment for
      telomere-proximal sequences.

PMID- 8575754
TI  - Molecular cloning, expression pattern, and chromosomal localization of human
      CDKN2D/INK4d, an inhibitor of cyclin D-dependent kinases.
AB  - Progression through the G1 phase of the cell cycle is dependent on the activity
      of holoenzymes formed between D-type cyclins and their catalytic partners, the
      cyclin-dependent kinases cdk4 and cdk6. p16INK4a, p15INK4b, and p18INK4c, a group
      of structurally related proteins, function as specific inhibitors of the cyclin D
      dependent kinases and are likely to play physiologic roles as specific regulators
      of these kinases in vivo. A new member of the INK4 gene family, murine INK4d, has
      recently been identified. Here we report the isolation of human INK4d (gene
      symbol CDKN2D), which is 86% identical at the amino acid level to the murine
      clone and approximately 44% identical to each of the other human INK4 family
      members. The INK4d gene is ubiquitously expressed as a single 1.4-kb mRNA with
      the highest levels detected in thymus, spleen, peripheral blood leukocytes, fetal
      liver, brain, and testes. The abundance of INK4d mRNA oscillates in a cell-cycle
      dependent manner with expression lowest at mid G1 and maximal during S phase.
      Using a P1-phage genomic clone of INK4d for fluorescence in situ hybridization
      analysis, the location of this gene was mapped to chromosome 19p13. No
      rearrangements or deletions of the INK4d gene were observed in Southern blot
      analysis of selected cases of pediatric acute lymphoblastic leukemia (ALL)
      containing a variant (1;19)(q23;p13) translocation that lacks rearrangement of
      either E2A or PBX1, or in ALL cases containing homozygous or hemizygous deletions
      of the related genes, INK4a and INK4b.

PMID- 8575755
TI  - Cloning, expression, and chromosomal localization of a novel cadherin-related
      protein, protocadherin-3.
AB  - To study the diversity of the protocadherin family, the cDNA clones for a novel
      protocadherin were isolated by screening rat brain cDNA libraries with a cDNA
      fragment obtained by PCR, and some of the properties were then characterized. The
      overall structure of the protein defined by the clone is similar to that of
      previously identified protocadherins; however, the cytoplasmic domain is distinct
      from those of previously cloned protocadherins or any other protein sequences in
      the data bank. We named this protocad herin-3 (Pcdh3) since this is the third
      protocadherin of which the entire coding sequence has been determined. Most of
      the deduced amino acid sequences of other cDNA clones obtained by the screening
      show high homology with but are distinct from that of Pcdh3, indicating that most
      of these sequences correspond to homologous but different protocadherins. These
      results demonstrate that Pcdh3 and the protocadherins defined by these clones
      constitute a protocadherin subfamily. Chromosome mapping indicates that mouse
      Pcdh3 is located in a specific region of mouse chromosome 18, close to the
      location of previously cloned protocadherins, suggesting that various
      protocadherins form a cluster in this region. In situ hybridization results
      showed that Pcdh3 and its related proteins were expressed at various areas in
      brain. The expressed Pcdh3 protein from the cDNA in mouse L cells was about 100
      kDa in molecular weight and was localized at cell-cell contact sites. In contrast
      to the classical cadherins, however, the expressed Pcdh3 was sensitive to trypsin
      even in the presence of Ca2+, and the transfectants did not show strong Ca(2+)
      dependent cell aggregation activity. These results indicate the structural and
      possibly functional diversity of the protocadherin family and suggest a
      distinctive biological role for Pcdh3.

PMID- 8575756
TI  - Two-dimensional DNA typing of human pedigrees: spot pattern characterization and
      segregation.
AB  - By two-dimensional (2-D) genome typing, i.e., electrophoretic separation of
      restriction enzyme-digested genomic DNA on the basis of both size and sequence in
      denaturing gradient gels followed by hybridization analysis, several hundred
      alleles (spots) can be analyzed in parallel, using a micro- or minisatellite core
      probe. We studied the segregation of 213 and 214 spots detected by microsatellite
      core probe (CAC)n and minisatellite core probe 33.6, respectively, in two three
      generation human pedigrees. Reproducibility of the spot patterns was such that
      particular spot variants could be scored in both pedigrees. Between 73 and 74% of
      the spots scored were variant and were transmitted in a Mendelian manner. Very
      little cosegregation among the 2-D spots themselves was observed, suggesting a
      random distribution over the genome. Several pairs of spots that appeared to
      contain both alleles from single loci were identified. The few spots detected by
      both probes (overlapping spots) showed different segregation patterns, indicating
      that each probe detects independent sets of genetically informative loci. These
      results provide a firm basis for using 2-D DNA typing to identify disease loci
      and for constructing a 2-D spot genetic linkage map of the human genome.

PMID- 8575757
TI  - Physical linkage of the human growth hormone gene cluster and the skeletal muscle
      sodium channel alpha-subunit gene (SCN4A) on chromosome 17.
AB  - The human growth hormone (GH) locus, a cluster of five genes, spans 47 kb on
      chromosome 17q22-q24. The skeletal muscle sodium channel alpha-subunit locus
      (SCN4A), a 32.5-kb gene, has previously been mapped to 17q23.1-q25.3. We
      demonstrate that both the GH gene cluster and the SCN4A gene colocalize to a
      single 525-kb yeast artificial chromosome (YAC) containing DNA derived from human
      chromosome 17. Restriction maps of two cosmids encompassing the 5' terminus of
      the GH locus and including up to 40 kb of 5'-flanking sequences demonstrate a
      perfect 20-kb overlap with previously published maps of the SCN4A gene. A 720-bp
      DNA segment, encompassing sequences 32.3 to 31.6 kb 5' to GH, was sequenced and
      found to be identical to exon 14 of SCN4A. These data demonstrate that the SCN4A
      gene and the entire GH gene cluster are contained within 100 kb on chromosome 17
      and are separated by only 21.5 kb. Remarkably, this physical linkage between GH
      and SCN4A also reveals that multiple elements critical to tissue-specific
      transcriptional activation of the GH gene lie within the SCN4A gene.

PMID- 8575758
TI  - Index, comprehensive microsatellite, and unified linkage maps of human chromosome
      14 with cytogenetic tie points and a telomere microsatellite marker.
AB  - Three sets of linkage maps (index, comprehensive microsatellite, and unified)
      have been constructed for human chromosome 14 based on genotypes from the CEPH
      reference pedigrees. The index maps consist of 18 microsatellite markers, with
      heterozygosities of at least 68% and intermarker spacing no greater than 11 cM.
      The sex-average comprehensive microsatellite map is 125 cM in length and includes
      115 markers with 54 loci uniquely placed with odds for marker order of at least
      1000:1. The sex-average index map length is 121 cM, and the female- and male
      specific maps are 143 and 101 cM, respectively. A unified map was also
      constructed from 147 loci (162 marker systems), which includes 32 RFLP markers in
      addition to the 115 microsatellites. The sex-average length of the unified map is
      128 cM with 69 loci uniquely placed. Our maps are anchored by a microsatellite
      telomere marker sCAW1 (D14S826), developed from a telomere YAC clone TYAC196,
      which extends the linkage map to the physical terminus of the long arm of
      chromosome 14. Furthermore, we have also physically mapped seven of the loci by
      fluorescence in situ hybridization of cosmid clones or Alu-PCR products amplified
      from YACs containing the marker sequences. Together with previously established
      cytogenetic map designations for other loci, our maps display links between
      genetic markers for 10 of 13 cytogenetic bands of chromosome 14 at the 550 genome
      band resolution.

PMID- 8575759
TI  - A 6-Mb yeast artificial chromosome contig and long-range physical map
      encompassing the region on chromosome 12q15 frequently rearranged in a variety of
      benign solid tumors.
AB  - Cytogenetic analysis of a variety of benign solid tumors, among which uterine
      leiomyoma, lipoma, pleomorphic salivary gland adenoma, and pulmonary chondroid
      hamartoma, has indicated that these tumors often display chromosome breakpoints
      in region q13-q15 of chromosome 12. In previous studies, we have reported that
      these breakpoints map between locus D12S8 and the CHOP gene, the latter of which
      has been shown to be consistently rearranged in myxoid liposarcomas with
      t(12;16)(q13;p11). Here, we report directional chromosome walking studies
      starting from D12S8 and resulting in the construction of a YAC contig of about 6
      Mb. This YAC contig, whose orientation on chromosome 12 was determined by double
      color fluorescence in situ hybridization (FISH) analysis, has at least double
      coverage and consists of 75 overlapping YAC clones, all isolated from CEPH YAC
      libraries. Their insert sizes were estimated by contour-clamped homogeneous
      electric field (CHEF) gel electrophoresis. Chromosomal localization and chimerism
      of the YACs were investigated by FISH analysis. Chimerism of YAC clones was
      independently determined by restriction mapping. On the basis of YAC end-derived
      DNA markers and sequence-tagged sites (STSs), with an average spacing of
      approximately 70 kb, as well as restriction enzyme analysis, a long-range
      physical map was established for the 6-Mb DNA region of chromosome 12 covered by
      the YAC contig. Within the YAC contig, the relative positions of various known
      genes, an expressed sequence-tagged site, and a number of CEPH/Genethon
      polymorphic markers were determined. The latter data allow full integration of
      our mapping data with those obtained by CEPH/Genethon as well as those reported
      at the Second International Workshop on Human Chromosome 12 Mapping. Finally,
      this YAC contig constitutes the basis for the contstruction of a transcriptional
      map of this region and is likely to facilitate identification of genes involved
      in the formation of various benign solid tumor types.

PMID- 8575760
TI  - Conservation of position and sequence of a novel, widely expressed gene
      containing the major human alpha-globin regulatory element.
AB  - We have determined the cDNA and genomic structure of a gene (-14 gene) that lies
      adjacent to the human alpha-globin cluster. Although it is expressed in a wide
      range of cell lines and tissues, a previously described erythroid-specific
      regulatory element that controls expression of the alpha-globin genes lies within
      intron 5 of this gene. Analysis of the -14 gene promoter shows that it is GC rich
      and associated with a constitutively expressed DNase 1 hypersensitive site;
      unlike the alpha-globin promoter, it does not contain a TATA or CCAAT box. These
      and other differences in promoter structure may explain why the erythroid
      regulatory element interacts specifically with the alpha-globin promoters and not
      the -14 gene promoter, which lies between the alpha promoters and their
      regulatory element. Interspecies comparisons demonstrate that the sequence and
      location of the -14 gene adjacent to the alpha cluster have been maintained since
      the bird/mammal divergence, 270 million years ago.

PMID- 8575762
TI  - The human protoporphyrinogen oxidase gene (PPOX): organization and location to
      chromosome 1.
AB  - We determined the structure of the human protoporphyrinogen oxidase (PPOX) gene
      after isolation and characterization of lambda phage clones mapping discrete
      regions of the cDNA. Southern blotting of human genomic DNA showed that there is
      a single copy of the PPOX gene, and fluorescence in situ hybridization to
      metaphase chromosomes mapped the gene to region 1q22. The gene has 13 exons and
      about 8 kb. The exon/intron boundary sequences conform to consensus acceptor
      (GTn) and donor (nAG) sequences, and exons in the gene appear to encode
      functional protein domains. Primer extension analysis revealed two major
      transcriptional initiation sites in a region with sequence motifs characteristic
      of a promoter. The promoter region contains multiple Sp1 elements, CCAAT boxes,
      and potential GATA-1 binding sites. Mapping of the 5' end PPOX mRNA by polymerase
      chain reaction indicated that there are the same transcripts in erythroid and
      nonerythroid cells.

PMID- 8575761
TI  - A new human gene located in the PKD1 region of chromosome 16 is a functional
      homologue to ERV1 of yeast.
AB  - A new human gene has been identified on chromosome 16 in the interval containing
      the locus for polycystic kidney disease (PKD1) by analysis of a genomic cosmid
      clone and cDNAs. The gene contains at least one intron and is actively
      transcribed in tissues from kidney and brain. The putative gene product is
      predicted to be homologous to the yeast scERV1 protein by virtue of the high
      degree of identity (42%) over the entire length of the polypeptides. In former
      studies the yeast scERV1 gene was found to be essential for oxidative
      phosphorylation, the maintenance of mitochondrial genomes, and the cell-division
      cycle. In this study a yeast expression vector with a chimeric reading frame
      coding for the first 21 amino acids of the yeast protein and the terminal 100
      amino acid residues of the human factor was transformed into yeast mutants with
      two different defects for scERV1. The chimeric human gene product was able to
      complement the yeast mutants and restored near normal viability. This identifies
      the human gene as a structural and functional homologue of the scERV1 gene.

PMID- 8575764
TI  - Assignment of the beta B1 crystallin gene (CRYBB1) to human chromosome 22 and
      mouse chromosome 5.
AB  - By using primers complementary to the rat beta B1 crystallin gene sequence, we
      amplified exons 5 and 6 of the orthologous human gene (CRYBB1). The amplified
      human segments displayed greater than 88% sequence homology to the corresponding
      rat and bovine sequences. CRYBB1 was assigned to the group 5 region in 22q11.2
      q12.1 by hybridizing the exon 6 PCR product to somatic cell hybrids containing
      defined portions of human chromosome 22. The exon 5 and exon 6 PCR products of
      CRYBB1 were used to localize, by interspecific backcross mapping, the mouse gene
      (Crybb1) to the central portion of chromosome 5. Three other beta crystallin
      genes (beta B2(-1), beta B3, and beta A4) have previously been mapped to the same
      regions in human and mouse. We demonstrate that the beta B1 and beta A4
      crystallin genes are very closely linked in the two species. These assignments
      complete the mapping and identification of the human and mouse homologues of the
      major beta crystallins genes that are expressed in the bovine lens.

PMID- 8575763
TI  - Regional chromosomal assignments for four members of the MADS domain
      transcription enhancer factor 2 (MEF2) gene family to human chromosomes 15q26,
      19p12, 5q14, and 1q12-q23.
AB  - The MEF2 genes belong to the MADS box family of transcription factors and encode
      proteins that bind as homo- and heterodimers to a consensus CTA(T/A)4TAG/A
      sequence, which is present in the regulatory regions of numerous muscle-specific
      and growth-inducible genes. Sequence analysis of human MEF2 cDNA clones suggests
      that they arose from alternatively spliced transcripts of four different genes,
      termed MEF2A-D. We have mapped the MEF2 genes to human chromosomal regions by
      identifying unique sequences in the MEF2 cDNA clones and using these sequences as
      PCR primers on the DNA of human-rodent hybrid clone panels that are informative
      for different regions of the human genome. PCR primers were also used to identify
      individual YAC clones for two of the genes, MEF2A and MEF2C, and a PCR product
      was used to identify cosmid clones for MEF2B. Genetic and physical mapping
      information available from genome databases on markers contained within YAC and
      cosmid clones provided independent assignments for those genes. Inter-Alu PCR
      painting probes of YAC clones were used as probes for high-resolution chromosomal
      regional assignment by fluorescence in situ hybridization. The localization of
      MEF2A to chromosome 15q26, MEF2B to 19p12, MEF2C to 5q14, and MEF2D to 1q12-q23
      verifies the existence of at least four distinct loci for members of this gene
      family.

PMID- 8575765
TI  - A curly-tail modifier locus, mct1, on mouse chromosome 17.
AB  - The major gene for neural tube defects, ct, in the curly-tail (CT) mouse strain
      was mapped previously to mouse chromosome 4 by combining linkage data from
      several backcrosses. The penetrance of the neural tube trait, already incomplete
      in the CT strain, was further reduced in several of these backcrosses, suggesting
      the existence of recessive modifiers or strain-specific susceptibility alleles.
      Here we describe the mapping of a curly-tail modifier locus, mct1, to chromosome
      17 in moderate and low penetrance crosses of CT with BALB/cByJ and Mus spretus.
      No effect of mct1 was seen in a higher penetrance cross with the BXD-8/Ty strain,
      confirming that ct is the major gene in the model. Homozygosity at both ct and
      mct1 loci was sufficient to account for all of the affected individuals in the
      BALB/cByJ cross and most of the affected individuals in the M. spretus cross and
      was the preferred model overall. No evidence was found for epistatic interaction
      between ct and mct1.

PMID- 8575766
TI  - The melanoma antigen gene (MAGE) family is clustered in the chromosomal band
      Xq28.
AB  - The melanoma antigen gene (MAGE) family comprises 12 known genes, of which 6 are
      expressed in tumors. In the course of a systematic analysis of transcripts in
      Xq28, we have identified cDNAs related to different MAGE genes. Analysis of cell
      hybrids, ordered YACs, and cosmids showed that all MAGE genes are located in Xq28
      and are clustered in three main intervals within 3.5 Mb. The six genes expressed
      in tumors are contained in the two intervals closest to the telomere and are
      highly homologous to each other. Analysis of different species suggests that
      human MAGE sequences are conserved in primates, but less well conserved in other
      vertebrate species.

PMID- 8575767
TI  - Human glucose phosphate isomerase: exon mapping and gene structure.
AB  - The structure of the gene for human glucose phosphate isomerase (GPI) has been
      determined. Three GPI clones were isolated from a human genomic library by using
      a full-length GPI cDNA probe and were characterized. Oligonucleotides based on
      the known cDNA sequence were used as primers in amplification and sequence
      analyses. This led to the identification of the exon-intron junctions. By this
      approach, 18 exons and 17 introns have been identified. The exons range in size
      from 44 to 431 nucleotides. The intronic sequences surrounding the exons provide
      useful information for the identification of mutations that give rise to human
      GPI deficiency associated with chronic hemolytic anemia.

PMID- 8575768
TI  - Cloning and characterization of the mouse glucokinase gene locus and
      identification of distal liver-specific DNase I hypersensitive sites.
AB  - We cloned and characterized an 83-kb fragment of mouse genomic DNA containing the
      entire glucokinase (GK) gene. The 11 exons of the gene span a total distance of
      49 kb, with exons 1 beta and 1L being separated by 35 kb. A total of 25,266 bp of
      DNA sequence information was determined: from approximately -9.2 to approximately
      +15 kb (24,195 bp), relative to the hepatocyte transcription start site, and from
      -335 to +736 bp (1071 bp), relative to the transcription start site in beta
      cells. These sequences revealed that mouse GK is > 94% identical to rat and human
      GK. Mouse hepatic GK mRNA is regulated by fasting and refeeding, as also occurs
      in the rat. Alignment of the upstream and downstream promoter regions of the
      mouse, rat, and human genes revealed several evolutionarily conserved regions
      that may contribute to transcriptional regulation. However, fusion gene studies
      in transgenic mice indicate that the conserved regions near the transcription
      start site in hepatocytes are themselves not sufficient for position-independent
      expression in liver. Analysis of the chromatin structure of a 48-kb region of the
      mouse gene using DNase I revealed eight liver-specific hypersensitive sites whose
      locations ranged from 0.1 to 36 kb upstream of the liver transcription start
      site. The availability of a single, contiguous DNA fragment containing the entire
      mouse GK gene should allow further studies of cell-specific expression of GK to
      be performed.

PMID- 8575769
TI  - Partial structure of the mouse glucokinase gene.
AB  - A complementary DNA for glucokinase (GK) was cloned from mouse liver total RNA by
      a combination of the polymerase chain reaction (PCR) and mouse liver cDNA library
      screening. Liver- and beta-cell-specific exons 1 were isolated by PCR using mouse
      and rat genomic DNAs. These clones were then used to screen a mouse genomic
      library; three genomic clones were isolated and characterized. The mouse GK gene
      spans over 20 kb, containing 11 exons including a liver- or beta-cell-specific
      exon 1, which encodes a tissue-specific 15-aa peptide at the N-terminus of the
      protein. Both types of GK contain 465 amino acid residues. The predicted amino
      acid sequence of mouse beta-cell-specific GK showed 98 and 96% identity to the
      rat and human enzymes, respectively; the corresponding values are 98 and 95%,
      respectively, for the liver-specific GK. Several transcription factor-binding
      consensus sequences are identified in the 5' flanking region of the mouse GK
      gene.

PMID- 8575770
TI  - Cloning and gene mapping of the mouse homologue of the CBFA2T1 gene associated
      with human acute myeloid leukemia.
AB  - The human CBFA2T1 (also known as MTG8) gene, on chromosome 8, has been identified
      through its involvement in the t(8;21) chromosomal translocation, frequently
      found in acute myeloid leukemia. We report here the isolation and
      characterization of the mouse homologue of the CBFA2T1 gene, Cbfa2t1h. Nucleotide
      sequence analysis of Cbfa2t1h cDNA clones revealed an open reading frame encoding
      a protein of 577 amino acids with an extremely high degree of amino acid identity
      (99.3%) to the human protein. The nucleotide sequence is also highly conserved
      between mouse and human in the 5'- and 3'-untranslated regions (87.0, 92.0, and
      93.7% identities for 5'-untranslated, coding, 3'-untranslated regions,
      respectively). The 3'-untranslated region of Cbfa2t1h contains a (CA)n
      dinucleotide repeat, and the polymerase chain reaction amplification of the (CA)n
      repeat region revealed fragment length polymorphism among mouse strains. Using
      this polymorphism, we have mapped Cbfa2t1h to mouse chromosome 4 close to the
      centromere using SMXA recombinant inbred strains and 106 intersubspecific
      backcross progenies of the (DBA/2 x Mae) x Mae cross. The chromosomal location
      was also confirmed by fluorescence in situ hybridization.

PMID- 8575771
TI  - Frequency and polymorphism of simple sequence repeats in a contiguous 685-kb DNA
      sequence containing the human T-cell receptor beta-chain gene complex.
AB  - The human T-cell receptor beta-chain (TCRB) gene complex spans 575 kb in
      chromosome region 7q35 and has been the subject of a large-scale DNA sequencing
      effort. A contiguous 685-kb DNA sequence from this region was searched by
      computer analysis for the occurrence of simple sequence repeats (microsatellites)
      with core sequence lengths of 2-5 nucleotides. Twenty-nine such microsatellites
      of repeat number n > or = 9 were found, with the majority being dinucleotide
      repeats. By PCR analysis, 19 were found to be polymorphic in repeat number, thus
      averaging one per 36 kb. These polymorphic di-, tri-, and tetranucleotide repeats
      had between 3 and 15 differently sized alleles each. The potential usefulness of
      these TCRB microsatellites for detecting disease susceptibility alleles was
      examined by measuring the linkage disequilibrium between these markers and
      flanking biallelic mutations. All but 4 microsatellites (79%) demonstrated
      significant linkage disequilibrium (P < 0.0001). This present study highlights
      the utility and potential outcomes of large-scale DNA sequencing for the
      identification of polymorphic simple sequence repeats.

PMID- 8575772
TI  - Physical mapping of the human ELA1 gene between D12S361 and D12S347 on chromosome
      12q13.
AB  - ELA1, the pancreatic elastase 1 gene, is conserved in mammalian genomes. ELA1 was
      previously mapped to chromosome 12 using a panel of mouse-human somatic cell
      hybrids. We now report the physical and cytogenetic localization of the ELA1
      gene. On the physical map, ELA1 is adjacent to the polymorphic marker AFMa283yg1
      and between D12S361 and D12S347. Using fluorescence in situ hybridization, we
      determined that ELA1 maps to 12q13.

PMID- 8575773
TI  - Locations of the ets subfamily members net, elk1, and sap1 (ELK3, ELK1, and ELK4)
      on three homologous regions of the mouse and human genomes.
AB  - Net, Elk1, and Sap1 are related members of the Ets oncoprotein family. We show by
      in situ hybridization on banded chromosomes with specific cDNA probes that their
      map positions on mouse and human chromosomes (respectively) are net, 10C-D1 and
      12q22-q23 (now called ELK3), sap1, 1E3-G and 1q32 (ELK4), and elk1, XA1-A3 and
      Xp11.2-p11.1 (ELK1), as well as a second locus 14q32 (ELK2) unique to the human
      genome. The results for the mouse net, sap1, and elk1 and human ELK3 genes are
      new. The human elk1 mapping confirms a previous study. The human ELK4
      localization agrees with data published during the preparation of the manuscript.
      Human ELK3 colocalizes with sap2, and we confirm that they are identical. These
      results firmly establish for the first time that Net, Elk1, and Sap1 are distinct
      gene products with different chromosomal localizations in both the mouse and the
      human genomes. Net, Elk1, and Sap1 are conserved and map to homologous regions of
      the mouse and human chromosomes.

PMID- 8575774
TI  - Human gastric inhibitory polypeptide receptor: cloning of the gene (GIPR) and
      cDNA.
AB  - Gastric inhibitory polypeptide (GIP), which is released from the gastrointestinal
      tract, stimulates insulin secretion from pancreatic beta cells and plays a
      crucial role in the regulation of insulin secretion during the postprandial
      phase. We have isolated the human gene (GIPR) and cDNA encoding the GIP receptor
      by a combination of the conventional screening and polymerase chain reaction
      procedures. Human GIP receptor cDNA encodes a protein of 466 amino acids that is
      81.5 and 81.2% identical to the previously cloned hamster and rat GIP receptor,
      respectively. Hydropathic analysis shows the presence of a signal peptide and
      seven potential transmembrane domains, a feature characteristic of the
      VIP/glucagon/secretin receptor family of G protein-coupled receptors. The human
      GIPR gene is about 13.8 kb long, consists of 14 exons, and carries 17 Alu
      repeats.

PMID- 8575775
TI  - Cloning and characterization of the neural isoforms of human dystonin.
AB  - Dystonia musculorum (dt) is a hereditary neurodegenerative disease in mice that
      leads to a sensory ataxia. We have identified and cloned a gene encoded at the dt
      locus. The product of the dt gene, dystonin, is a neural isoform of a
      hemidesmosomal protein bullous pemphigoid antigen 1 (bpag1). To investigate the
      potential role of dystonin in human neuropathies, we have cloned the neural
      specific 5' exons of the human DT gene that together with the previously cloned
      BPAG1 sequences comprise human dystonin. The mouse and human dystonin genes
      demonstrate the same spectrum of alternatively spliced products, and the amino
      acid sequences of the neural-specific exons in the mouse and human genes are over
      96% identical.

PMID- 8575776
TI  - Genetic linkage mapping of the dehydroepiandrosterone sulfotransferase (STD) gene
      on the chromosome 19q13.3 region.
AB  - In the human liver and adrenal, there is a single hydroxysteroid
      sulfotransferase, which catalyzes the transformation of dehydroepiandrosterone to
      dehydroepiandrosterone sulfate, the most abundantly circulating steroid in
      humans, and also catalyzes the sulfation of a series of other 3 beta
      hydroxysteroids as well as cholesterol. Dehydroepiandrosterone sulfate serves as
      precursor for the formation of active androgens and estrogens in several
      peripheral tissues, indicating that hydroxysteroid sulfotransferase plays a
      pivotal role in controlling the hormonal action of sex steroids by regulating
      their bioavailability. We recently elucidated the structure of the gene encoding
      hydroxysteroid sulfotransferase (STD), also designated dehydroepiandrosterone
      sulfotransferase, which spans 17 kb and contains six exons. The STD gene was
      preliminarily assigned to chromosome 19 by polymerase chain reaction (PCR)
      amplification of DNA from a panel of human/rodent somatic cell hybrids. To locate
      the STD gene, the novel biallelic polymorphism found in intron 2 was genotyped in
      eight CEPH reference families by direct sequencing of PCR products. Two-point
      linkage analysis was first performed between the latter polymorphism and
      chromosome 19 markers from Genethon and NIH/CEPH. The closest linkage was
      observed with D19S412 (Zmax = 9.23; theta max 0.038) and HRC (Zmax = 5.95; theta
      max 0.036), located on the 19q13.3 region. A framework map including six Genethon
      markers flanking the polymorphic STD gene was created by multipoint linkage
      analysis. Thereafter, a high-resolution genetic map of the region was
      constructed, yielding to the following order: qter-D19S414-D19S224-D19S420
      D19S217-(APOC2++ +-D19S412)- (STD-HRC)-KLK-D19S22-D19S180-PRKCG-D19S418 -tel.

PMID- 8575777
TI  - Epithelial sodium channel genes Scnn1b and Scnn1g are closely linked on distal
      mouse chromosome 7.
AB  - The chromosomal localizations of Scnn1b and Scnn1g, genes corresponding to the
      beta- and gamma-subunits, respectively, of an epithelial non-voltage-gated
      amiloride-sensitive sodium channel, were determined by analyses of two sets of
      multilocus crosses using probes generated by polymerase chain reaction and a
      mouse kidney cortical collecting tubule cell line (M1). Scnn1b and Scnn1g were
      determined to be closely linked on distal mouse chromosome 7, showing no
      recombination with Zp2, whereas the gene for the alpha-subunit, Scnn1a, was
      confirmed to map to distal mouse chromosome 6.

PMID- 8575778
TI  - Characterization of a YAC contig spanning the pseudoautosomal region.
AB  - Due to its unique biology of partial sex linkage and high recombination rates,
      the pseudoautosomal region (PAR1) on both X and Y chromosomes has attracted
      considerable interest. In addition, an extremely high level of YAC instability
      has been observed in this region. We have derived 82 YAC clones from six
      different YAC libraries mapping to this 2.6-Mb region. Of these a subset of 22
      YACs was analyzed in detail. YAC contigs were assembled using 67 pseudoautosomal
      probes, of which 64 were unambiguously ordered. All markers are well distributed
      over the entire region, including the middle part of the region, which has
      previously been found difficult to contig. Two gaps of less than 50 kb within the
      genomic locus of CSF2RA and around XE7 remain, which could not be covered with
      YACs, cosmids, or phages. This YAC contig anchored on the physical map of PAR1
      represents one of the best characterized large regions of the human genome with a
      map completion greater than 90% at 100-kb resolution and has permitted the
      accurate localization of all known genes within this region.

PMID- 8575779
TI  - Chromosomal location of murine protein tyrosine phosphatase (Ptprj and Ptpre)
      genes.
AB  - It is now widely accepted that protein tyrosine phosphatases (PTPases) play
      important or even critical roles in cell growth, differentiation, and
      development. Our recent experiments suggested that specific PTPases, PTP beta 2
      and PTP epsilon, are involved in the early molecular events for in vitro
      differentiation of mouse erythroleukemia (MEL) as well as embryonic carcinoma
      (F9) cells. Using mouse cDNA for PTP beta 2 and PTP epsilon, which we have cloned
      recently, we attempted to locate the genes to mouse chromosomes. Interspecific
      backcross analysis indicated that the gene for PTP beta 2, Ptprj, is located in
      the middle region of chromosome 2, and the gene for PTP epsilon, Ptpre, was
      mapped in the vicinity of the imprinted regions in the distal part of chromosome
      7. Possible biological roles of these PTPases are discussed.

PMID- 8575780
TI  - Expression analysis, genomic structure, and mapping to 7q31 of the human sperm
      adhesion molecule gene SPAM1.
AB  - During the course of systematic sequence tag analysis of clones isolated from an
      adult testis cDNA library, clones 296 and 576 were found to detect 71-74%
      sequence identity to the guinea pig sperm surface protein PH-20. This surface
      protein is involved in sperm-egg adhesion in the guinea pig. Nucleotide sequence
      for 1919 bp of human DNA from a series of overlapping cDNA clones isolated from a
      testis cDNA library confirmed the sequence identity within a 1527-bp open reading
      frame to be 71-74% to the guinea pig gene and the similarity to be 60% for the
      predicted protein of 509 amino acids. Southern blot analysis of human genomic DNA
      and DNA from somatic cell hybrids indicates that the gene (SPAM1) is unique and
      does not form part of a larger family and that it maps to chromosome 7.
      Fluorescence in situ hybridization with yeast artificial chromosome (YAC) clones
      isolated from the CEPH megaYAC library has refined this localization to 7q31. PCR
      analysis of genomic DNA and YAC clone DNA has shown that the 1919 bp of the gene
      that has been cloned covers approximately 11 kb of genomic DNA and is encoded by
      at least 4 exons. Northern analysis of poly(A)+ mRNA from a range of 16 human
      tissues has demonstrated that expression of the gene as a single 2.4-kb
      transcript is strictly limited to the testis.

PMID- 8575781
TI  - Head to tail organization of the human COL6A1 and COL6A2 genes by fiber-FISH.
AB  - Two type VI collagen genes, COL6A1 and COL6A2, both map to 21q22.3, but the
      order, distance, and organization of these two genes relative to one another were
      not known. Recently developed high-resolution fluorescence in situ hybridization
      (FISH) techniques have great potential to facilitate the construction of fine
      resolution maps of telomeric regions where gene density is high. Here we have
      determined the distance separating the COL6A1 and COL6A2 genes (150 kb), the size
      of the COL6A1 gene (29 kb); and the 5'-3' orientation of these genes (5' COL6A1
      3'-5' COL6A2 3') using fiber-FISH.

PMID- 8575782
TI  - Structure and chromosomal localization of the GPI-anchor synthesis gene PIGF and
      its pseudogene psi PIGF.
AB  - Posttranslational modification by the GPI glycolipid anchor is essential for the
      surface expression of many membrane proteins. Defect of GPI biosynthesis due to
      somatic mutation in the hematopoietic stem cell is the basis for an acquired
      genetic disease, paroxysmal nocturnal hemoglobinuria (PNH). Previously, an X
      linked gene PIGA (phosphatidylinositol glycan class A), which participates in the
      first step of the biosynthesis, was shown to be mutated in abnormal cells from
      all 60 patients with PNH. The cDNA of another GPI synthesis gene PIGF was
      previously cloned, but it is not involved in pathogenesis of PNH. In the present
      study, we have analyzed PIGF genomic clones. The PIGF gene contained six exons
      spanning about 40 kb and was located to the short arm of chromosome 2 at 2p16
      p21. The frequency of mutations on both alleles of PIGF should be much lower than
      that of mutation in the X-linked PIGA, accounting for a lack of involvement of
      PIGF in PNH. We also identified the processed pseudogene of PIGF (psi PIGF) and
      mapped it to 5q35.

PMID- 8575783
TI  - Assignment of human G-protein-coupled inward rectifier K+ channel homolog GIRK3
      gene to chromosome 1q21-q23.

PMID- 8575784
TI  - Assignment of human myocyte-specific enhancer binding factor 2C (hMEF2C) to human
      chromosome 5q14 and evidence that MEF2C is evolutionarily conserved.

PMID- 8575785
TI  - The human FGF9 gene maps to chromosomal region 13q11-q12.

PMID- 8575786
TI  - Mapping of the Sca1 and pcd genes on mouse chromosome 13 provides evidence that
      they are different genes.

PMID- 8575787
TI  - Chromosomal localization of the mitochondrial phosphate carrier gene PHC to
      12q23.

PMID- 8575788
TI  - Genetic mapping of a gene encoding an atypical protein kinase C, protein kinase C
      lambda, to the proximal region of mouse chromosome 3.

PMID- 8575789
TI  - Localization of the gene encoding the secretin receptor, SCTR, on human
      chromosome 2q14.1 by fluorescence in situ hybridization and chromosome
      morphometry.

PMID- 8575791
TI  - Inhibition of staphylococcal enterotoxin-driven lymphocyte proliferation by anti
      MHC class II monoclonal antibody.
AB  - Staphylococcal enterotoxins (SE) bind to major histocompatibility complex (MHC)
      class II molecules and the V beta region of T cell receptors (TCR) and
      subsequently induces T cell proliferation. This mitogenicity is the basis of
      pathological effects seen in food poisoning and toxic shock syndrome. Toxin
      specific monoclonal antibodies have previously been shown to be effective in
      blocking toxin stimulated T cell responses. In this study, a monoclonal antibody,
      52BL1, was found to be a potent inhibitor of SEA-, SEB-, SEC1-, SED-, and SEE
      induced lymphocyte proliferation assays, which indicates that a single anti-HLA
      (human leukocyte antigen) class II antibody is effective in blocking the
      biological effects of these toxins. These results demonstrate the possibility of
      using anti-HLA class II antibodies in a clinical setting as an antagonist to
      staphylococcal enterotoxinmediated pathogenesis.

PMID- 8575790
TI  - Studies on natural ST2 gene products in the human leukemic cell line UT-7 using
      monoclonal antihuman ST2 antibodies.
AB  - Eight species of murine monoclonal antibodies against human ST2 protein, which is
      highly similar in protein sequence to the interleukin 1 receptor, were produced.
      The fusion was carried out between the murine myeloma cell line PAI and murine
      lymph node or spleen cells from mice immunized with the recombinant ST2 protein
      produced in Escherichia coli. Characterization of these monoclonal antibodies by
      immunoblot analysis revealed that they all reacted with recombinant, N
      glycosylated ST2 protein that was secreted from COS7 cells transiently
      transfected with a mammalian expression vector carrying ST2 cDNA. The recombinant
      N-glycosylated ST2 protein could be immunoprecipitated by 5 out of 6 species of
      the IgG class monoclonal antibodies. Furthermore, these antibodies were also able
      to detect, by immunofluorescence, the membrane-bound chimeric molecule possessing
      an extracellular portion of human ST2 and a transmembrane and cytoplasmic portion
      of murine receptor type ST2L expressed on COS7 cells, indicating that these
      monoclonal antibodies were useful for detecting the natural membrane-bound ST2 in
      human cells. Combining immunoprecipitation and immunofluorescence with the aid of
      these monoclonal antibodies, together with the reverse transcriptase-polymerase
      chain reaction method, the human leukemic cell line UT-7 was demonstrated to
      express human ST2 mRNA and protein. The identification of the ST2 gene product in
      UT-7 cells may help investigators elucidate the function of the human ST2 gene.

PMID- 8575792
TI  - Epitopic analysis and quantification of bovine myoglobin with monoclonal
      antibodies.
AB  - Seven rat monoclonal antibodies (MAb) for bovine myoglobin were produced. Five
      antibodies reacted with surface-absorbed myoglobin whereas the two remainders
      reacted only in a sandwich type ELISA. The ability of different antibodies to
      bind simultaneously to myoglobin was examined by competition and additivity
      experiments and three noncompeting epitope regions were found. A two-site enzyme
      immunoassay was developed and allowed quantification of 30 ng/ml bovine
      myoglobin. These antibodies should be valuable tools in comparative studies for
      immunological reactivity of mammalian myoglobins and for myoglobin measurement in
      serum and urine of myopathic animals.

PMID- 8575793
TI  - Cloning and expression of a single-chain antibody fragment specific for a
      monomorphic determinant of class I molecules of the human major
      histocompatibility complex.
AB  - B9.12.1 is a monoclonal antibody specific for a monomorphic determinant of human
      MHC class I molecules. It is currently used for cell typing and is useful for
      targeting infection of human cells by murine ecotropic retroviruses. We have
      cloned and expressed it in the form of a single-chain variable fragment (ScFv)
      that recognizes the same epitope as the parental antibody. Through genetic
      engineering, this ScFv may be used for developing new cell-typing probes and new
      retroviral targeting approaches.

PMID- 8575794
TI  - Isolation and characterization of a monoclonal antibody binding to the
      extracellular domain of the flk-2 tyrosine kinase receptor.
AB  - The flk-2 tyrosine kinase receptor is expressed on hematopoietic stem cells and
      on acute leukemias (AML and ALL). We have isolated a rat monoclonal antibody
      (71E1) that binds to this receptor with a relative affinity of 5 nM. The antibody
      immunoprecipitates both murine and human forms of flk-2 and can block receptor
      activation by its cognate ligand. In addition, 71E1 inhibits the in vitro
      proliferation of the murine leukemic cell line, M1, that expresses high levels of
      flk-2. These results suggest that 71E1 may have utility as both a reagent for
      elucidating the biological role of flk-2 in hematopoiesis and as an
      immunotherapeutic in the treatment of acute leukemias.

PMID- 8575796
TI  - Isolation and characterization of neutralizing monoclonal antibodies to human
      vascular endothelial growth factor/vascular permeability factor121 (VEGF/VPF121).
AB  - We have established monoclonal antibodies (MAbs) against human vascular
      endothelial growth factor/vascular permeability factor121 (VEGF/VPF121). Two
      (MV101 and MV303) of the 28 MAbs neutralized the mitogenic activity of
      VEGF/VPF121 on human umbilical vein endothelial cells (HUVEC) in a dose-dependent
      manner. Both of the MAbs reacted to VEGF/VPF121 and also VEGF/VPF165 with
      somewhat different binding properties in a sandwich-type enzyme-linked
      immunosorbent assay (ELSIA). The binding of MV101 and MV303 to VEGF/VPF121 was
      competitive, but MV415, another anti-VEGF/VPF121 MAb without neutralizing
      activity, did not complete with either of the antibodies. MV101 and MV303
      specifically recognized the native form of VEGF/VPF121 and VEGF/VPF165 in Western
      blotting. They did not react with VEGF/VPF when the antigens were fractionated
      under reducing conditions. These observations suggested that MV101 and MV303
      might recognize the epitopes closely located on the configuration of VEGF/VPF121
      molecule and the epitopes recognized by MV101 and MV303 may play an important
      role in the VEGF/VPF-receptor signal transduction. These MAbs significantly
      suppressed the growth of a human hepatoma, PLC/PRF/5, in vivo.

PMID- 8575797
TI  - Membrane-associated and cytosolic species-specific antigens of Mycoplasma bovis
      recognized by monoclonal antibodies.
AB  - Mycoplasma bovis is a causative agent of bovine mastitis, arthritis, and
      pneumonia. Six monoclonal antibodies (MAbs) against M. bovis were prepared and
      used to characterize specific antigens of the mycoplasma. Reactivity of the MAbs
      to six M. bovis strains was tested by IFA, ELISA, and immunoblotting. The
      specificity of these MAbs was tested by the same methods against 8 other species
      of bovine mycoplasmas and 1 mycoplasma species of sheep and goats (Mycoplasma
      agalactiae) that is highly cross-reactive with M. bovis. Three of the MAbs were
      used on Western blots of trypsin-treated whole organisms to determine if the
      antigens were exposed on the surface of M. bovis By isotyping, MAbs were
      identified as kappa chain IgG1 (3 MAbs), and IgM (3MAbs). The MAbs reacted with
      all six M. bovis strains in IFA, ELISA, and Western blots. Four of the antigens
      recognized were highly specific for M. bovis in ELISA, and 3 were cross-reactive
      with M. agalactiae or other bovine mycoplasmas in Western blots. One MAb reacted
      with multiple bands with all M. bovis strains, indicating recognition of a size
      variant antigen. The size-variant antigen and one of the M. bovis-specific
      antigens were recognized as surface proteins. A large M. bovis-specific antigen
      was a conserved cytosolic protein. The M. bovis antigens discovered may be used
      for specific detection of the organism or measurement of antibody responses,
      particularly if used in tests with nondenatured alkali-treated antigen, such as
      ELISA.

PMID- 8575798
TI  - Production of a monoclonal antibody to an antigen present on both trophoblasts
      and leukocytes.
AB  - In the present study, we report the establishment of a monoclonal antibody (Mab)
      designated F10 that recognized an antigen commonly shared by human trophoblasts
      and leucocytes. F10 MAb was obtained using cell membrane components from a
      trophoblast cell line HT as immunogen. Based on immunochemical studies, the F10
      reactive antigen (F10-Ag) could be located on both villous and nonvillous
      trophoblasts from early and term placental tissues and on all trophoblastic cell
      lines. In addition, flow cytometry revealed that most ( > 95%) peripheral blood
      lymphocytes, monocytes, as well as polymorphonuclear leukocytes (PMN) were
      positively stained with F10 MAb. Immunoblotting with F10 MAb identified two
      protein bands with apparent molecular mass of 62 and 56 kDa. Furthermore, the
      antigens were glycoproteins and were glycosylated via the O-linkage. Scatchard
      plot analyses of the binding data between 125I-labeled MAb F10 IgG and HT cells
      revealed a single class of F10 binding sites with an apparent dissociation
      constant (Kd) of 10.54 +/- 2.03 pM and maximum binding-site (Bmax) value of 2.1
      +/- 0.11 x 10(6) sites per cell. We suggest that F10 may be useful for the
      identification of a novel epitope that is commonly shared by all trophoblasts and
      leukocytes and such an epitope may be potentially active in maternal-fetal
      interactions.

PMID- 8575795
TI  - Generation, characterization, and in vivo studies of humanized anticarcinoma
      antibody CC49.
AB  - Monoclonal antibody (MAb) CC49 reacts with tumor-associated glycoprotein (TAG)
      72, a human pancarcinoma antigen. In clinical trials, radiolabeled CC49 has shown
      excellent tumor localization; however, many of the patients receiving MAb CC49
      develop a human antimouse antibody response. In an attempt to prevent this
      antiimmunoglobulin response, we have developed a humanized CC49 (HuCC49) by
      grafting the MAb CC49 hypervariable regions onto the variable light (VL) and
      variable heavy (VH) frameworks of the human MAbs LEN and 21/28' CL, respectively,
      while retaining those murine framework residues that may be required for the
      integrity of the antigen combining-site structure. The HuCC49 MAb was compared
      with native murine CC49 (nCC49) and chimeric CC49 (cCC49), using a variety of
      assays. SDS-PAGE analysis under nonreducing conditions showed that the HuCC49 MAb
      has virtually identical mobility to that of cCC49. Under reducing conditions, the
      HuCC49 yielded two bands of approximately 25-28 and approximately 50-55 kDa,
      characteristic of heavy and light immunoglobulin chains. In competition
      radioimmunoassays, HuCC49 completely inhibited the binding of 125I-labeled nCC49
      to TAG-72, although 23- to 30-fold more HuCC49 was required to achieve a level of
      competition similar to those of cCC49 and nCC49. The relative affinity of HuCC49
      was 2- to 3-fold less than those of the cCC49 and nCC49 MAbs, respectively. The
      plasma clearance in mice of HuCC49 was virtually identical to that of cCC49.
      Biodistribution studies demonstrated equivalent tumor-targeting of HuCC49 and
      cCC49 to human colon carcinoma xenografts. These studies thus suggest that HuCC49
      and genetically modified molecules, such as sFv and domain-deleted
      immunoglobulins developed by using the HuCC49 variable region as a cassette, may
      be potentially useful in both diagnostic and therapeutic clinical trials in
      patients with TAG-72-positive tumors.

PMID- 8575799
TI  - Cell cluster formation during up-scaling of a human-mouse heterohybridoma
      producing a polyspecific human IgM antibody.
AB  - Up- and downstream processing of human monoclonal IgM is known to bring about
      problems with respect to clone stability and quantity of antibodies produced. A
      human B cell hybridoma producing a natural polyreactive IgM antibody (CB03) was
      adapted to growth in serum-free medium and scaled-up using a hollow fiber
      bioreactor system. The process of fermentation has been carried out continuously
      over a period of 4 months. In comparison to stationary culture conditions in the
      presence of 10% fetal calf serum, antibody concentrations in hollow fiber
      bioreactor supernatants were found to be significantly increased.
      Semicontinuously harvested supernatants contained up to 400 mg/liter
      immunoreactive IgM antibody. During the last weeks of fermentation, a markedly
      reduced number of viable cells was observed, whereas antibody production seemed
      to remain stable. Furthermore, we detected formation of cell clusters in the
      fermentor system. These clusters carried IgM on the surface and secreted
      immunoreactive IgM antibodies. Clusters were found to represent fusions of
      hybridoma cells using electron microscopy. Cluster formation was accompanied by
      decreased glucose consumption and lactate accumulation and was not seen during
      growth of other human hybridomas. We discuss these results in the content of the
      polyreactive binding properties of this particular antibody.

PMID- 8575800
TI  - Diagnostic relevance of silver stained nucleolar organizer region (AgNORs) in
      benign and malignant breast lesions.
AB  - The present study is planned to assess the diagnostic relevance of silver stained
      nucleolar organizer regions (NORs) in discriminating benign from malignant
      lesions of the breast and to ascertain the interobserver variability in the
      enumeration of AgNOR counts. Forty four specimens of benign and malignant breast
      tissues were studied and mean number of silver stained nucleolar organizer
      regions (MNORA) have been counted in paraffin sections. Malignant lesions have a
      higher number of MNORA than benign lesions. These results also showed correlation
      between the AgNOR counts and size of the tumor, axillary lymph node status and
      age of the patient. Our results also indicate a close agreement between the two
      observers with limits of agreement. However, AgNOR counts are of little
      diagnostic importance since a broad zone of overlap exists between benign and
      malignant breast diseases despite significant higher mean counts in malignant
      lesions. AgNOR sequence could perhaps be of use to differentiate those two
      histological indistinguishable lesions. The tumor size and axillary lymph node
      involvement suggested to its prognostic significance also. Interobserver
      agreement further suggests the utility of AgNOR counts as diagnostic or
      prognostic discriminants in breast malignancies.

PMID- 8575801
TI  - Effect of hematoporphyrin derivative and light on sulfhydryl groups in brain
      tumour cells.
AB  - Effect of hematoporphyrin derivative (HpD) and light on sulfhydryl (SH) groups in
      brain tumor cells was studied. Sulfhydryl groups were measured by 5,5'-dithiobis
      (2-nitrobenzoic acid) (DTNB) and a fluorescent probe 3,4-maleimidylphenyl-4
      methyl-7-diethylaminocoumarin (CPM). Incubation of cells with HpD in dark
      resulted in the loss of DTNB as well as CPM reactive SH groups. After 2 hr of
      incubation DTNB reactive SH groups showed a negligible change while a continuous
      decrease was observed in CPM reactive SH groups. Cells treated with HpD showed a
      further degradation of SH groups upon light irradiation. A comparison of
      cytotoxicity and SH groups under identical conditions showed that blockage of SH
      groups by HpD binding is not leathal to the cells where as photoinduced cell
      death was observed on photodegradation of SH groups.

PMID- 8575802
TI  - Changes in epididymal structure and function of albino rat treated with
      Azadirachta indica leaves.
AB  - The histological and biochemical changes in the caput and cauda epididymis of
      albino rat treated with 20, 40 and 60 mg dry powder of the leaves of A. indica
      per day for 24 days are reported. In the treated rats, the height of the
      epithelium and the diameter of the nucleus in both the regions were reduced. The
      lumen of the caput was packed with lymphocytes. Biochemically, a decrease in the
      protein content and acid phosphatase activity and an increase in the alkaline
      phosphatase and lactate dehydrogenase activities were observed in both the
      regions. The effect was dose dependent. Further, serum testosterone concentration
      in the higher dose treated animals decreased significantly. The results suggest a
      possible antiandrogenic property of the leaves of A. indica.

PMID- 8575803
TI  - Effects of bleomycin and Staphylococcus protein-A on lungs of mice.
AB  - Fibrosis of organs and tissues are major causes of morbidity and mortality in
      human. The currently available pharmacologically based treatments are
      unsatisfactory. As an experimental animal model antitumor antibiotic drug
      bleomycin (BLM) is widely used to produce lung fibrosis. The present study has
      been undertaken to investigate the possible role of a potent immunomodulator
      Staphylococcus protein-A (SpA) in the modulation of lung lesions caused by
      treatment of BLM. In mice BLM, 0.5 mg in 200 microliters of normal saline and
      SpA, 6 micrograms in 200 microliters of normal saline was administered singly or
      in combination twice a week for 4 weeks. The fibrotic lesions in the lungs were
      observed after 4 weeks of BLM treatment. After 4 weeks treatment of SpA, the
      hyperreactive changes in bronchi and bronchioles were observed. In the co
      treatment group of BLM and SpA, the effects observed were in the form of enhanced
      lesions in the lung parenchyma. Moreover, the pleural lesions were also observed
      in co-treatment group (BLM + SpA). Opposite to the assumption, SpA being a potent
      immunomodulator was not able to reduce the lung lesions produced by BLM.

PMID- 8575804
TI  - Influence of dietary protein on DDT-induced immune responsiveness in rats.
AB  - The influence of protein deficiency was evaluated on immune responsiveness after
      subchronic DDT exposure in albino rats. Rats were given 20%, 12% and 3% protein
      diets and exposed to DDT (20, 50 or 100 ppm) for 4 weeks. DDT (50 and 100 ppm)
      induced humoral and cellular immune suppression only in rats fed on 3% protein
      diet. There was (a) an increase in the albumin/globulin ratio, (b) suppression in
      IgM and IgG levels, and (c) attenuation in the tetanus toxoid-induced antibody
      responses. Further, in rats immunized with tetanus toxoid, the leucocyte and
      macrophage migration inhibition were also attenuated. Moreover, these animals
      maintained on 3% protein diet showed depression in humoral and cellular immune
      responses to antigen in a dose-dependent pattern after exposure to DDT at dose
      levels which were not immunosuppressive for rats on 12% or 20% protein diet.
      These results suggest that dietary protein content may predispose to the
      immunotoxic effects of DDT exposure, and also be a crucial determinant in DDT
      detoxification.

PMID- 8575805
TI  - Development of biosensor for glucose estimation by ion sensitive field effect
      technique.
AB  - In order to provide a better understanding of the Ion Sensitive Field Effect
      Devices (ISFED) as a biosensor, the C-V characteristics and the change in the
      flat band voltage of Electrolyte-Insulator-Semiconductor (Electrolyte-SiO2-Si) in
      response to pH are examined. The response of silicon oxynitride as an insulator
      to pH in EIS has better response compared to that of SiO2. The application of C-V
      characteristics of EIS as a biosensor for glucose estimation, is investigated.
      For this purpose glucose oxidase is immobilized on the surface. The change in the
      capacitance of this system (biased at constant voltage) to different
      concentrations of glucose is measured. The output response of differential
      capacitance shows a linear response to the variation of glucose concentration,
      thus providing a technique which could be used as a biosensor.

PMID- 8575806
TI  - Effects of S-allyl cysteine sulfoxide isolated from Allium sativum Linn and
      gugulipid on some enzymes and fecal excretions of bile acids and sterols in
      cholesterol fed rats.
AB  - S-allyl cysteine sulfoxide, isolated from garlic, A. sativum, is more or less as
      active as gugulipid in controlling hypercholestermia, obesity and derangement of
      enzyme activities in cholesterol diet fed rats. The beneficial effects of the
      drugs are partly due to their inhibitory effects on transaminases, alkaline
      phosphatase, lipogenic enzymes and HMG CoA reductase and partly due to their
      stimulatory effects on plasma lecithin-cholesterol acyl transferase lipolytic
      enzymes and fecal excretion of sterols and bile acids.

PMID- 8575807
TI  - Effect of orally administered betel leaf (Piper betle Linn.) on digestive enzymes
      of pancreas and intestinal mucosa and on bile production in rats.
AB  - The influence of two varieties of betel leaf (Piper betle Linn.) namely, the
      pungent Mysore and non-pungent Ambadi, was examined on digestive enzymes of
      pancreas and intestinal mucosa and on bile secretion in experimental rats. The
      betel leaves were administered orally at two doses which were either comparable
      to human consumption level or 5 times this. The results indicated that while
      these betel leaves do not influence bile secretion and composition, they have a
      significant stimulatory influence on pancreatic lipase activity. Besides, the
      Ambadi variety of betel leaf has a positive stimulatory influence on intestinal
      digestive enzymes, especially lipase, amylase and disaccharidases. A slight
      lowering in the activity of these intestinal enzymes was seen when Mysore variety
      of betel leaf was administered, and this variety also had a negative effect on
      pancreatic amylase. Further, both the betel leaf varieties have shown decreasing
      influence on pancreatic trypsin and chymotrypsin activities.

PMID- 8575808
TI  - Response of gravid Phlebotmus papatasi females to an oviposition
      attractant/stimulant associated with conspecific eggs.
AB  - Oviposition response of gravid P. papatasi females to conspecific eggs was
      studied in laboratory colonized sandflies. It was observed that significantly
      higher number of eggs were laid in the vicinity of conspecific eggs. However, a
      certain minimum number of eggs were required to be placed on the substratum to
      influence the rate of oviposition. The fecundity of females (mean = 56.5 +/- 4.9
      eggs) exposed to conspecific eggs was significantly higher (P < 0.05) than that
      of blank control group. Perhaps, the chemical substances/pheromone of egg origin
      stimulated the oviposition rate. In an attempt to isolate the active ingredient,
      solvent washing of the conspecific eggs were tested. No increase in the rate of
      oviposition was noticed when the test site was treated with distilled water
      extract, whereas, significantly larger number of eggs were laid at the site
      treated with di-ethyl ether extract. This indicated that the oviposition
      attractant associated with the eggs dissolved in the organic solvent, but not in
      water. The possible application of this attractant for wild sandflies in nature
      and for regulating the site of oviposition on the substratum in the laboratory
      colonized sandflies needs to be explored.

PMID- 8575809
TI  - Subcellular distribution of oxygen free radical scavenging enzymes in goat ovary.
AB  - Oxygen free radical scavenging enzymes superoxide dismutase (SOD), peroxidase
      (POD) and catalase were heterogeneously distributed in goat ovary. Activities of
      SOD and catalase were predominantly located in cytosolic fractions compared to
      mitochondrial and microsomal fractions. Most of the peroxidase activity was
      observed in microsomal fractions with little activity in cytosolic and
      mitochondrial fractions. Higher activities of all these enzymes were in luteal
      phase as compared to follicular phase. Most of the activities of these enzymes in
      luteal phase were restricted to luteal cells while in follicular phase these were
      mainly present in the follicles of the ovary.

PMID- 8575810
TI  - Alteration in alkaline phosphatase activity of duodenal tissue following
      vestibulo-cerebellar modulation.
AB  - Effect of electrolytic lesion in vestibulo-cerebellar area of male Wistar rats
      was investigated on duodenal alkaline phosphatase (AP) activity.
      Histomorphological observations of brain indicated, that extensive lesion
      restricted to the wide area of nodule including ventral uvula, resulted in
      significant fall of AP activity at the mucosal brush border within 20 days. A
      comparative behavioural study in experimental and control groups by openfield
      test indicated that, sympathoexcitation resulting from vestibulo-cerebellar
      lesion may contribute to significant alteration of AP activity in duodenum of
      rats.

PMID- 8575811
TI  - Insulin-mimetic effect of (-) epicatechin on osmotic fragility of human
      erythrocytes.
AB  - (-) Epicatechin, a benzopyran extracted from the bark of Pterocarpus marsupium,
      is reported to have insulin like activity. The present work is undertaken to
      study the effect of insulin on erythrocyte osmotic fragility (OF) and then to
      evaluate the insulin-like role of (-) epicatechin on human erythrocytes. Insulin
      exerts a protective effect on erythrocyte OF and shows a dose response which is
      similar to other typical insulin effects i.e. a maximum at 0.1 nM and a lower
      effect at higher and lower concentration. (-) Epicatechin (1 mM) also shows
      protective effect, similar to insulin, on the OF. Ouabain (1 mM) has completely
      abolished the insulin effect on OF, and failed to have any effect on the action
      of (-) epicatechin, showing that (-) epicatechin and insulin act by a different
      mechanism of action while eliciting their protective effects on red cell OF.

PMID- 8575812
TI  - Modulation of humoral immune response by tannery effluent in Oreochromis
      mossambicus (Peters).
AB  - Fish were treated with various sublethal concentrations of tannery effluent. A
      concentration-dependent suppression of both primary and secondary antibody
      responses to bovine serum albumin (BSA) was observed after primary or secondary
      immunization. The fish were able to compensate the effluent-induced suppression
      of antibody response when the antigen (BSA) was administered along with an oil
      adjuvant.

PMID- 8575813
TI  - Pulmonary phospholipid changes induced by butylated hydroxy toluene, an
      antioxidant, in rats.
AB  - Butylated hydroxy toluene (BHT), 800 mg/kg body weight, dissolved in corn oil and
      administered (ip) in a single injection to male rats, damaged the lung as
      indicated by an increase in lavage ACE, protein and LDH and caused a significant
      increase in phospholipid, particularly, phosphatidyl choline (PC) in lung lavage
      and extracellular surfactant. The plasma lecithin cholesterol acyl transferase
      (LCAT) activity was inhibited leading to an increase in serum phospholipids and
      phosphatidyl choline. The results indicate that BHT-induced lung phospholipidosis
      may be attributed to an increase in surfactant phospholipids and/or due to the
      leakage of plasma phospholipids through damaged capillary membrane.

PMID- 8575814
TI  - Effect of D-400, a herbomineral preparation on lipid profile, glycated
      haemoglobin and glucose tolerance in streptozotocin induced diabetes in rats.
AB  - This study was undertaken to investigate D-400, a herbomineral formulation in
      streptozotocin induced diabetes in rats. Glycated haemoglobin, lipid profile and
      glucose tolerance test were studied. D-400 has an established hypoglycaemic
      effect in alloxan induced diabetes in rats as well as in non-insulin dependent
      diabetes mellitus patients. D-400 treated group showed lower glycated
      haemoglobin, triglycerides and higher HDL levels. The hyperglycaemic response was
      blunted after administration of oral glucose in the same group.

PMID- 8575815
TI  - Physical map of the HLA-A/HLA-F subregion and identification of two new coding
      sequences.
AB  - As part of an effort to characterize the hemochromatosis gene, we selected three
      non-chimeric yeast artificial chromosomes (YACs) overlapping with the YAC B30
      previously described and forming an 800 kilobase contig covering the HLA-A/HLA-F
      region. The precise physical map of these YACs and of the corresponding genomic
      region were established. Nine concentrated sites of CpG cutter elements,
      potentially HTF islands, were mapped. In addition, several probes have been
      generated as tools for mapping and examining transcripts produced in the region.
      This allowed for the characterization and localization of two new coding
      sequences, provisionally named HCG (for hemochromatosis candidate gene) and
      numbered VIII and IX.

PMID- 8575816
TI  - Stem-loop potential in MHC genes: a new way of evaluating positive Darwinian
      selection?
AB  - The domains of polymorphic major histocompatibility complex (MHC) proteins which
      interact with peptides and T-cell receptors are considered to have been under
      positive evolutionary selection pressure. Evidence for this is a high ratio of
      non-synonymous to synonymous mutations in the corresponding genomic domains. By
      this criterion snake venom phospholipase A2 genes have also been under positive
      selection pressure. Recent studies of the latter genes indicate that positive
      selection has overridden an evolutionary pressure on base order which normally
      promotes the potential to extrude single-strand stem-loops from supercoiled
      duplex DNA ( fold pressure ). This has resulted in base order-dependent stem-loop
      potential being shifted to introns, which are highly conserved between species.
      It is now shown that, like snake venom phospholipase A2 genes, the domains of
      polymorphic MHC genes which appear to have responded to positive selection
      pressure have decreased base order-dependent stem-loop potential. The
      evolutionary pressure to generate stem-loop potential (believed to be important
      for recombination) has been overridden less in exons under negative purifying
      selection than in exons under positive Darwinian selection. Thus, base order
      dependent stem-loop potential shows promise as an independent indicator of
      positive selection.

PMID- 8575817
TI  - Molecular cloning and sequencing of interleukin 6 cDNA fragments from the harbor
      seal (Phoca vitulina), killer whale (Orcinus orca), and Southern sea otter
      (Enhydra lutris nereis).
AB  - Using polymerase chain reaction, interleukin-6 (IL-6) cDNA fragments from harbor
      seal (Phoca vitulina), killer whale (Orcinus orca), and Southern sea otter
      (Enhydra lutris nereis) were cloned and sequenced. For all three species, a
      continuous open reading frame encoding 203 residues for harbor seal, 199 residues
      for killer whale, and 201 residues for sea otter with stop codons located at
      analogous positions were identified. These fragments correspond to nucleotides 71
      - 753 of the human IL-6 transcript and represent 96% of the complete coding
      nucleotides. Comparison of these marine mammal sequences with other published
      mammalian IL-6 cDNA demonstrated that both harbor seal and sea otter IL-6 had
      most similarity to that of other terrestrial carnivores (Mustelidae and Canidae),
      while killer whale had highest identity with ruminants (Bovidae and Ovidae).
      Among the three marine mammal species characterized, as well as cDNA sequences
      from nine other species, 40 invariant amino acids, including a number of residues
      situated at the putative gp80 and gp130 receptor binding sites, were identified.
      The presence of invariant amino acids within the receptor-binding portion of IL-6
      for twelve different species suggests these positions are essential for
      biological activity of IL-6 and, moreover, likely account for the cross
      reactivity among different mammalian IL-6-like activities in mouse bioassays. An
      additional significant finding was the presence of several variant residues only
      within the mouse putative IL-6 receptor binding region, which may account for
      observations of restricted cross-reactivity of mouse IL-6-like activity in human
      bioassays. Together, these findings provide insights into the evolution of the
      mammalian IL-6 gene and additional valuable information regarding amino acid
      residues essential for the biological activity of mammalian IL-6.

PMID- 8575818
TI  - The human T-cell receptor gamma variable pseudogene V10 is a distinctive marker
      of human speciation.
AB  - The V10 variable gene of the human T-cell receptor gamma locus (TCRG-V10), the
      only member of the subgroup III, has a structural defect which inhibits the
      splicing of the leader intron. We show that there is a single point mutation in
      the V10 leader donor splice site responsible for this situation and that this
      mutation is found in the different populations tested, indicating that V10
      corresponds to a pseudogene in humans. We restored the splice site by mutagenesis
      and obtained correct splicing in vitro. Analysis of the V10 germline gene in
      different primates reveals functional splice sites in the closest human apes, the
      chimpanzee and the gorilla. The splice competence of TCRG-V10 in higher primates
      was addressed in peripheral blood lymphocytes from chimpanzee by specific cDNA
      amplification, and correct splicing of the TCRG-V10 leader intron was found as
      well as a majority of in frame rearrangements involving only the TCRG-J1 or J2
      segments. These results suggest that V10(+)gamma /delta T cells may represent an
      important subset in the non-human higher primates, contrary to the situation
      observed in the human.

PMID- 8575820
TI  - Two genes controlling acute phase responses by the antitumor polysacch aride,
      lentinan.
AB  - Lentinan, a beta-1,6;1,3-glucan, is tumor-specific for transplantable mouse solid
      type tumors and it also stimulates the production of acute phase proteins (APPs).
      The APP response to lentinan is of the delayed type (DT-APR) and differs from
      that to lipopolysaccharide, which is acute. We found that the responses were
      genetically controlled in mice and that low responsiveness is dominant (Maeda et
      al. 1991). Using 123 segregants of crosses between SWR/J (a high responder) and
      Mus spretus (a low responder), we analyzed the linkage between DT-APR
      responsiveness and the DNA polymerase chain reaction-simple sequence length
      polymorphism (PCR-SSLP) phenotype using 80 chromosome-specific microsatellite
      markers. We identified two loci (ltn1.1 and ltn1.2) responsible for DT-APR.
      ltn1.1 is closely linked to D3Mit11 on chromosome 3 and ltn1.2 to D11Nds9 on
      chromosome 11 (P <0.001). The linkage analysis also suggested that ltn1.2 is the
      major determinant for DT-APR. Correlation between lentinan-specific IL-6 mRNA
      expression (the late expression) controlled recessively and DT-APR induction
      suggests that the ltn1 loci control some process(es) of IL-6 expression in the
      regulation step before NF-IL6.

PMID- 8575819
TI  - Genomic organization of a mouse MHC class II region including the H2-M and Lmp2
      loci.
AB  - The region encompassing the Ma, Mb1, Mb2, and Lmp2 genes of the mouse class II
      major histocompatibility complex (MHC) was sequenced. Since this region contains
      clusters of genes required for efficient class I and class II antigen
      presentation, it was interesting to search for putative additional genes in the
      21 kilobase gap between the Mb1 and Lmp2 genes. Computer predictions of coding
      regions and CpG islands, exon trapping experiments, and cross-species comparison
      with the corresponding human sequence indicate that no additional functional gene
      is present in that stretch. However, computer analysis revealed the possible
      existence of an alternative 3' exon for Mb1. Except for the fact that the mouse
      MHC contains two Mb genes, the genomic organization of the H2-M loci was found to
      be almost identical to the organization of the human HLA-DM genes. The promoter
      regions of the Ma and Mb genes also resemble classical class II promoters,
      containing typical S, X, and Y boxes. Like the human genes, the three H2-M genes
      displayed very limited polymorphism when we compared the cDNA sequences from six
      haplotypes. Finally, comparison of DMB with Mb1 and Mb2, both at the genomic
      level and in their coding regions, suggests that the Mb gene was recently
      duplicated, probably only in certain rodents.

PMID- 8575821
TI  - Chromosomal mapping of the second human CD8B gene locus.

PMID- 8575822
TI  - The CG-1 gene, a member of the kinectin and ES/130 family, maps to human
      chromosome band 14q22.

PMID- 8575823
TI  - Nucleotide sequence of a human MHC class I MICB cDNA.

PMID- 8575824
TI  - Cloning and partial characterization of the mouse B7-1 promoter.

PMID- 8575825
TI  - Peptide motifs from three cattle MHC (BoLA) class I antigens.

PMID- 8575826
TI  - A new HLA-DRB1(*)13 allele (DRB1(*)1318) with a short DRB1(*)08 sequence.

PMID- 8575827
TI  - Nucleotide sequence of a new HLA-DRB1(*)11 allele (DRB1(*)1124).

PMID- 8575828
TI  - A new HLA-B35 (B*3516) allele found in a Mexican of Nahua (Aztec) descent.

PMID- 8575829
TI  - Alternatively spliced forms of the human myeloid Fc alpha receptor (CD89) in
      neutrophils.

PMID- 8575830
TI  - Sequencing of a new HLA-DR14 allele (DRB1(*)1422).

PMID- 8575831
TI  - Complete sequence of the complement C4 gene from the HLA-A1, B8, C4AQ0, C4B1, DR3
      haplotype.

PMID- 8575832
TI  - Sequence of two cattle MHC class I cDNAs associated with BoLA A10 specificity.

PMID- 8575834
TI  - Retrovirus-induced lymphoproliferative disease in mice undergoing graft-versus
      host reaction.
AB  - The effect of graft-versus-host reaction on the course of concommitant retrovirus
      induced lymphoproliferative disease was investigated. The graft-versus-host
      reaction was elicited by a single i.v. injection of 1.2 x 10(8) parental spleen
      cells into adult F1 mice. Lymphoproliferative disease was induced by a single
      transfusion of 0.2 ml of whole blood from donors with fully developed disease,
      induced by infection with retrovirus LP-BM5 MuLV. Graft-versus-host reaction and
      the lymphoproliferative disease each separately produced similar syndrome
      consisting of splenomegaly, lymphadenopathy, leukopenia, neutrophilia, reduced in
      vitro proliferation of spleen cells and suppression of in vivo immune
      responsiveness. The above symptoms were usually less pronounced during graft
      versus-host reaction. Ongoing graft-versus-host reaction neither aggravated nor
      accelerated the course of the virus-induced lymphoproliferative disease in
      genetically susceptible F1 hybrids. Likewise, an ongoing graft-versus-host
      reaction in genetically resistant F1 hybrids did not alter their susceptibility
      to the retrovirus infection. The apparent lack of the effect of graft-versus-host
      reaction -dependent immunosuppression on the severity and the course of the
      concommitant retrovirus-induced lymphoproliferative disease suggests pathogenic
      differences between the murine syndrome and human AIDS for which the murine
      disease is considered by some to be an animal model.

PMID- 8575835
TI  - CD8+ T cell subsets in aging.
AB  - Infections are major cause of illness and death amongst elderly people.
      Peripheral blood CD8+ T lymphocytes -which play a crucial role in host defence
      against viral infections-. are divided in subsets based upon the expression of
      several cell and activation markers. Since in senescence changes in peripheral
      blood CD8+ T lymphocyte compartment have been described, studies were performed
      to determine whether in aging there are variations in the peripheral blood
      CD8+CD38+, CD8+CD57+, CD8+HLA-DR+, CD8+CD45RA+ and CD8+CD45RO+ cell subset. A
      decrease in the CD8+CD45RA+ lymphocytes was observed, indicating that variations
      in the CD8+ compartment can take place with ageing.

PMID- 8575833
TI  - Characterization of an inhibitory seric factor from tuberculosis anergic patients
      that acts on non-adherent PPD reactive cells.
AB  - Non-adherent cells from PPD+ tuberculosis patients (TBP PPD+) and from healthy
      individuals treated with whole tuberculosis anergic immune sera or with its
      protein A-Sepharose IgG fraction, or with sera fraction separated by PPD
      Sepharose chromatography, were submitted to immunofluorescence assays. Anti-human
      IgG or IgM FITC-conjugate were used to reveal the assays, and results were
      expressed by a fluorescence percentage or fluorescence index. The presence of IgG
      over the surface of PPD+ non-adherent cells was detected. High fluorescence
      percentages were observed only in those PPD+ cells treated with whole anergic
      serum or with its IgG fraction. Positive fluorescence index values were obtained
      only in those PPD+ cells treated with anergic serum, meanwhile fluorescence index
      was always negative when non-bound fractions from PPD-Sepharose were used.
      Results suggest that non-adherent population are the cell targets for the serum
      inhibitory factor, which previously has been detected to inhibit antigen response
      in PPD reactive cells and, point out the specific behavior of this factor, since
      it was eliminate by PPD-Sepharose chromatography. The IgG nature of the factor
      was demonstrated by SDS-PAGE and immunoelectrophoresis.

PMID- 8575836
TI  - Monocyte-mediated regulation of antigen-driven IFN gamma production by T cells.
      The role of endogenously produced TNF.
AB  - The question was asked whether tumour necrosis factor alpha (TNF) is involved in
      regulation of interferon gamma (IFN gamma) production by T cells. Monocytes were
      exposed to exogenous TNF or to TNF synthesis inhibitors (pentoxifylline, PTX and
      adriamycin, ADR) and then used as antigen (PPD) presenting cells for autologous T
      cells. The ability of T lymphocytes to release IFN gamma was assessed after 3
      days of culture. Preincubation of monocytes with rTNF enhanced their ability to
      induce IFN gamma production while TNF synthesis inhibitors decreased it. Anti-TNF
      and anti-TNF-R2 monoclonal antibodies (mAbs) inhibited monocyte ability to
      present PPD for IFN gamma production which suggested that endogenously produced
      TNF by monocytes had to be released and acted on TNF-R2 on the monocyte surface.
      The enhancing effect of exogenous TNF was also abrogated by anti-TNF-R2 mAb.
      Pretreatment of monocytes with rTNF enhanced, while pretreatment with PTX
      decreased, PPD-induced IL-6 production. An increased production of IL-4 was found
      in cultures of PTX-treated, PPD-pulsed monocytes with T cells. This may indicate
      that in the relative absence of monocyte costimulatory signal(s), probably IL-6,
      Th2 cells are stimulated. These results indicate that TNF is involved in control
      of monocyte-mediated regulation of cytokine production by T cells.

PMID- 8575837
TI  - Characterization of an anti-CD44 single-chain FV antibody that stimulates natural
      killer cell activity and induces TNF alpha release.
AB  - We report the functional characterization of a single-chain Fv (scFv) constructed
      from an anti-CD44 mAb (S5) that abrogates marrow rejection in a mismatched canine
      donor transplant model. The variable light chain (VL) and variable heavy chain
      (VH) domains of the parent anti-CD44 antibody were cloned and exact match PCR
      primers designed that spliced the mature variable domains together through a 15
      amino acid [Gly4Ser]3 linker-encoding sequence. This gene was put under the
      control of a T7 promoter and expressed in Escherichia coli in insoluble inclusion
      bodies. The scFv was refolded in a cystine/cysteine redox buffer and purified to
      homogeneity using anion exchange chromatography. The concentration-dependent
      binding isotherm of the S5 scFv was determined using both direct binding and
      competitive inhibition flow cytometry assays. S5 scFv effectively blocked FITC
      conjugated MAb S5 binding to canine peripheral blood mononuclear cells (PBMC),
      possessing a mean EC50 (15 nM) equivalent to Fab' fragments of parental S5 (14.7
      nM) and approximately two-fold higher than Mab S5 (6 nM). It also binds directly
      to canine PBMC and possesses a mean EC50 similar to that of the Fab' fragments
      (1.01 nM vs 1.03 nM). The recombinant S5 scFv also retains the potent biological
      activity of the parent Mab, stimulating the activation of natural killer (NK)
      cell activity and the release of tumor necrosis factor alpha (TNF alpha) in
      canine PBMC. Like the parent antibody, scFv crossreacted with human CD44 as
      examined by direct binding to human PBMC in the flow cytometry assay as well as
      direct binding to human CD44 immunoglobulin fusion protein in an enzyme-linked
      immunosorbent assay (ELISA). It was also able to induce TNF alpha release in
      human PBMC. These results support previous work suggesting that monovalent
      binding is sufficient to generate the in vitro biological activity of S5 (1). The
      scFv S5 antibody will thus serve as a useful model for elucidating the mechanism
      of antibody abrogated marrow rejection and may serve as a human therapeutic
      agent.

PMID- 8575838
TI  - Abrogation of the allelic exclusion in a T cell receptor beta chain gene
      transgenic mouse strain.
AB  - The expression of endogenous T cell receptor (TcR) beta chains in a TcR beta
      chain gene transgenic mouse (TGM) strain was examined. Unlike many other TGM
      strains reported, a considerable proportion of T cells from the thymus and spleen
      as well as organ cultured fetal thymus from our TGM express endogenous TCR beta
      chains on their surface. Compatible with this was the elucidation of VDJ
      rearrangement of endogenous beta chain genes by PCR. Three color flow cytometric
      analysis of thymus cell subpopulations revealed that the expression levels of
      both endogenous and transgenic TcR beta genes are regulated in a maturational
      stage specific manner. Splenic T cells contained a several fold higher percentage
      of endogenous TcR beta positive cells than thymus cells, suggesting a role of TcR
      on T cell peripherization. V beta 6 positive cells were deleted in the TGM
      carrying minor lymphocyte stimulating (Mls)-la antigen, indicating that the
      endogenous TcR beta is functional in terms of transmitting a signal for clonal
      deletion.

PMID- 8575839
TI  - V gamma (I) expression in human intestinal lymphocytes is restricted.
AB  - The majority of human intestinal intraepithelial lymphocytes (HIELS) express
      CD8+, and the T cell Receptor (TCR) alpha beta. A minority of HIELS utilize TCR
      gamma delta chains. V delta 1 is established as the TCR-delta expressed by most
      TCR gamma delta HIELS. Since V delta 1 is the dominant intestinal TCR and V gamma
      (I) family is preferentially used in forming a heterodimer, this study was
      conducted to characterize individual V gamma (I) utilization in HIELS. Intestinal
      lymphocytes were isolated from four samples of colonic epithelium obtained from
      patients undergoing colon resection or endoscopy. RNA was isolated and cDNA
      synthesized. PCR amplification was performed with consensus J gamma and V gamma
      primers in these regions. PCR products were cloned and sequenced. All samples had
      V gamma 4 transcripts, a majority V gamma 3 whereas V gamma 2 and V gamma 8 were
      less frequent. No V gamma 2 transcripts had any predicted TCR protein products.
      Similarly, very few potentially productive V gamma 3 transcripts were found. In
      contrast, almost all V gamma 4 transcripts were found to be in-frame and the only
      V gamma 8 transcript was in-frame. The CDR3 region of the gamma transcripts were
      small compared to published intestinal TCR delta recombinations. All CDR3 regions
      contained at least one charged amino acid. The limited number of functional
      transcripts adds evidence to the oligoclonality of intestinal TCRs expressing the
      TCR V gamma (I) family. The short CDR3 regions support the concept of limited
      antigen recognition by this lymphocyte population.

PMID- 8575840
TI  - Mycobacterium tuberculosis antigen, interleukin 2 and interleukin 2 inhibitor in
      patients with rheumatoid arthritis.
AB  - IL-2 production by the phytohemaglutinin (PHA)-stimulated mononuclear cells (MNC)
      of peripheral blood (PB) and synovial fluid (SF) from patients with rheumatoid
      arthritis (RA), other arthritic diseases (OAD) and age-matched normal controls
      were studied, and the activity of IL-2 inhibitor in sera of studied subject was
      examined. The significant decreased IL-2 production by PB MNC from the patients
      with RA (p < 0.05) and OAD (p < 0.05) were observed when compared with normal
      controls, and no statistical difference was found although IL-2 levels in RA PB
      were lower than in OAD PB. However, significant statistical difference (p < 0.01)
      was found when the IL-2 production by RA SF was compared with OAD SF. Serum IL-2
      inhibitory factor was examined by IL-2-dependent mouse helper T cell line (HT-2).
      Significantly higher inhibitory activity was found in RA patients (p = 0.001)
      compared to OAD and normal control patients. Mycobacterium tuberculosis (MT)
      antigen was also examined from patients with RA and OAD, and 55.5% of SF from RA
      patients were positive for MT antigens and none was detected in OAD by a highly
      specific and sensitive double-antibody sandwich ELISA. However, no correlation
      between MT antigens, IL-2 levels and IL-2 inhibitory activities were found in
      patients with RA. Our results and other indicate that rheumatoid SF MNC, IL-2
      inhibitor and MT antigen may play important roles in the pathogenesis of RA.

PMID- 8575841
TI  - Effect of CD80 and CD86 on T cell cytokine production.
AB  - Conjugation of the T cell receptor (TCR) with antigen/MHC proteins must be
      accompanied by conjugation of T cell counterreceptors (CD28 or CTLA-4) with
      costimulatory molecules CD80 or CD86 (B7-1 or B7-2) on antigen presenting cells
      (APC) to avert T cell anergy, and to provide essential signals for T cell
      activation and cytokine production. However, T cells and APC express changing
      patterns of counterreceptors and costimulatory molecules during the immune
      response. To determine the involvement of CD80 and CD86 in costimulation of T
      cell cytokine production, T cells were incubated with peritoneal exudate
      macrophages, which express CD80 and CD86, and stimulated in vitro for 48 or 72
      hrs with anti-CD3 in the presence or absence of blocking antibody to CD80 or
      CD86. Alternatively, enriched anti-CD3 stimulated T cells were costimulated with
      antibody to CD28 and CTLA-4. Production of T cell IL-2, IL-4, and IL-5 was
      depressed in the presence of anti-CD86 but not anti-CD80. Production of IFN-gamma
      was significantly blocked by either anti-CD80 and anti-CD86. Anti-CD28 was a
      potent costimulator of IFN-gamma and IL-2 production, but a less potent
      costimulator of IL-4 and IL-5 production. The data suggest that T cell
      counterreceptors and APC costimulatory molecules act with varying efficacies at
      stimulating production of T cell cytokines.

PMID- 8575842
TI  - Interferon gamma potentiates human coronavirus OC43 infection of neuronal cells
      by modulation of HLA class I expression.
AB  - HCN-1A, a human cerebral cortical neuron cell line, was examined for its
      susceptibility to human coronaviruses. The 229e strain replicated efficiently,
      but the OC43 strain did not replicate well, if at all. Treatment of the cells
      with interferon gamma at 20U/ml for 48 hr markedly increased the susceptibility
      of the cells to infection with OC43 virus as shown by a 100-fold increase in
      secretion of infectious virus over a four day period as compared to untreated
      controls. The increased susceptibility was shown to be due to membrane expression
      of HLA class I by receptor-blockade with a monoclonal antibody specific for HLA
      molecules.

PMID- 8575843
TI  - Altered in vitro handling of Mycobacterium avium complex by monocytes and serum
      from HIV(+) patients.
AB  - In patients with acquired immunodeficiency syndrome (AIDS), mycobacterial
      diseases are leading opportunistic infections. The reasons for the peculiar
      propensity for disseminated infection with Mycobacterium avium complex (MAC)
      remain unclear. We have previously examined, in detail, the ability of monocytes
      from healthy donors to take up and kill MAC under both nonopsonic and opsonic
      conditions. We have now evaluated the in vitro ability of peripheral blood
      monocytes from HIV(+) patients to take up and kill MAC organisms, and have
      discovered a reduced ability under both nonopsonic and opsonic conditions. This
      reduction is due to: 1) apparent defect(s) in the phagocytes themselves, and 2)
      substance(s) in the HIV(+) serum which actively suppresses phagocyte activity.

PMID- 8575844
TI  - The effect of human cord blood on SJL/J mice after chemoablation and irradiation
      and its possible clinical significance.
AB  - There is evidence from the existing published literature that human umbilical
      cord blood, when used for purposes of bone marrow transplantation, does not
      necessarily have to be HLA matched in order to be efficacious. These reports
      include experimental observations on the ability of human umbilical cord blood to
      rescue lethally irradiated mice and clinical observations from China wherein HLA
      mismatched umbilical cord blood has been engrafted successfully in children with
      malignant disease. The study reported herein describes an experimental
      immunocompetent murine model to determine if human umbilical cord blood can be
      used to improve survival after chemoablation and irradiation. The animals
      received chemoablation followed by irradiation, and irradiation alone. The
      presence of human DNA in these mice following injection of human umbilical cord
      blood cells was determined, and the immunological status of the animals was
      evaluated. Animals receiving human umbilical cord blood cells after chemoablation
      and irradiation had a better mean survival at day 50 than animals receiving
      syngeneic marrow. Human DNA could be found in various organs, particularly the
      lung, spleen and liver of the mice for the first 30 days. Thereafter, human DNA
      became more difficult to detect but trace amounts of human DNA could be found up
      to one year later. The results of mixed lymphocyte reactions and phenotype
      analyses for murine T cell markers performed after injection of HUCB cells both
      indicated endogenous repopulation, and relatively intact immune systems in these
      mice. Since human umbilical cord blood allowed mice to survive the lethal effects
      of chemoablation plus irradiation, or irradiation alone, with reconstitution of
      the animals' own, relatively intact, immune systems, it would appear that HLA
      mismatched human umbilical cord blood could potentially be used as an adjuvant
      treatment for patients with advanced malignancies or other diseases for which
      hematopoietic reconstitution is indicated.

PMID- 8575845
TI  - Cancer mortality in relatives of women with breast cancer: the OPCS Study. Office
      of Population Censuses and Surveys.
AB  - Mortality from cancer and other causes in male and female first-degree relatives
      of women with breast cancer diagnosed before age 60 has been examined in a large
      population-based cohort study, providing estimates of familial risks free from
      ascertainment or recall bias. Relatives of 3,295 patients with breast cancer
      diagnosed in the UK between 1954 and 1981 were identified through a register of
      households established in 1939. The 11,678 first-degree relatives thus identified
      were followed up through national records until the end of 1992. Over this period
      5,421 deaths (including 1,527 cancer deaths) occurred in these relatives.
      Mortality from breast cancer was significantly raised in first-degree relatives
      (SMR 187, 248 deaths), and there was also significant excess mortality from
      cancers of the larynx (SMR 177, 17 deaths), endometrium (SMR 166, 29 deaths) and
      unspecified neoplasms (SMR 153, 70 deaths). The SMR for ovarian cancer was 130,
      based on 58 deaths (p = 0.06). There was no marked excess for other sites or for
      non-neoplastic causes of death, but there was a significant deficit in mortality
      from cervical cancer (SMR 63, 18 deaths). The SMR for breast cancer increased
      significantly with decreasing age of the relative. After allowing for age,
      sisters of cases had a slightly (though non-significantly) higher risk than
      mothers (ratio of SMRs 1.22). These results, together with penetrance estimates
      from linked families, suggest that approximately one woman in 800 carries BRCAI,
      the susceptibility gene on chromosome 17q, and that this gene causes about 1% of
      all breast cancers.

PMID- 8575846
TI  - Cancer mortality in relatives of women with ovarian cancer: the OPCS Study.
      Office of Population Censuses and Surveys.
AB  - Mortality from cancer and other causes in first-degree relatives of women with
      ovarian cancer diagnosed before age 60 has been examined in a large population
      based cohort study in England and Wales. Relatives of 1,188 ovarian-cancer cases
      diagnosed between 1954 and 1981 were identified through a register of households
      established in 1939. Some 4,111 first-degree relatives living in the same
      household and having the same surname as the index case were followed up through
      national records until the end of 1992. Over this period, 1,950 deaths (including
      574 cancer deaths) occurred in the relatives. Mortality rates within the cohort
      were compared with age-, sex- and period-adjusted mortality rates for England and
      Wales. Mortality from ovarian cancer in first-degree relatives was significantly
      raised (SMR 223, 95% CI 155-310) although the excess was smaller than that found
      in case-control studies. The SMR increased with decreasing age of the relative,
      though not with decreasing age of the index case. After allowing for age, sisters
      of cases had higher ovarian-cancer mortality than mothers (sister:mother SMR
      ratio 1.89, p = 0.06). The SMR was greater in individuals having 2 first-degree
      relatives with ovarian cancer (4 deaths versus 0.17 expected, SMR 242). Relatives
      of ovarian cancer cases also had significantly increased mortality from cancers
      of the stomach (SMR 146, 69 deaths) and rectum (SMR 150, 33 deaths), and
      increased mortality from colon cancer, breast cancer and pancreatic cancer which
      failed to reach statistical significance. Individuals having a relative with
      colorectal cancer and a relative with ovarian cancer showed a high mortality from
      both cancers (11 colorectal-cancer deaths versus 1.23 expected, 4 ovarian-cancer
      deaths versus 0.66 expected.

PMID- 8575847
TI  - Sialyl Tn antigen is an independent predictor of outcome in patients with gastric
      cancer.
AB  - The prognostic value of the immunohistochemical expression of Sialyl Tn antigen
      (STn) was evaluated in 242 patients with gastric carcinoma. Formalin-fixed,
      paraffin-embedded specimens of gastric adenocarcinomas were stained with the
      monoclonal antibody C1282, produced by immunization with ovine submaxillary mucin
      (OSM). Positive immunoreactivity for STn was observed in 149 (62%) patients. The
      expression of STn did not correlate with stage of disease (TNM), tumour location,
      presence of lymph-node or distant metastases, histological type, age or gender.
      STn immunoreactivity correlated strongly with overall survival in univariate
      analysis. The median survival in the STn-positive group was 21 months, in
      comparison to 38 months in the STn-negative group. The difference in survival
      between STn-negative and STn-positive tumours was significant in patients with
      stage-I cancer, but not in patients with stage-II -III or -IV disease. STn
      immunoreactivity emerged as an independent prognostic factor in Cox multivariate
      analysis. It is concluded that the immunohistochemical expression of STn is a
      good marker in the prediction of survival in patients with stage-I gastric
      carcinoma.

PMID- 8575848
TI  - Loss of chromosome 11 and 11 p/q imbalances in bladder cancer detected by
      fluorescence in situ hybridization.
AB  - To identify chromosomal imbalances in non-diploid transitional-cell carcinoma
      (TCC) of the bladder we performed double-target in situ hybridization (FISH),
      using the centromeric probe for chromosome 11 together with 2 cosmid probes
      located on the 11p and 11q arm in the proximity of the telomere. The FISH
      protocol was optimized to ensure a highly efficient and reproducible
      detectability of all 3 targets. As a consequence, it was possible to calculate
      ratios between the number of spots obtained with cosmid and centromere probes.
      Furthermore, the number of chromosomes 11 present was compared with the DNA index
      and the chromosome ploidy as obtained with other chromosome centromere probes. In
      this study we found that: (i) in 54 diploid TCCs a monosomy for chromosome 11 was
      detected in only one case; (ii) chromosome 11 was completely lost in 9 of 16 non
      diploid TCCs; (iii) in 8 of these 16 non-diploid tumors an imbalance was observed
      between the 11p and 11q arm, in 4 of these cases a complete loss of chromosome 11
      being observed in addition; (iv) the copy number counted for 11q was always
      identical to the 11 centromere number, except in one case, indicating a loss of
      11p in the cases with imbalances. In total, 13 of 16 non-diploid TCCs (81%)
      showed either a loss of a complete chromosome 11, of (part of) the 11p arm, or
      both. Therefore we concluded that during tetra- or aneuploidization in TCCs,
      (part of) chromosome 11 is lost. In addition, our results indicate that under
      representation of chromosome 11p occurs in the majority of the tumor cells,
      supporting the idea that loss of these sequences is an important step in the
      development of TCC.

PMID- 8575849
TI  - Tobacco and diet as determinants of survival in male laryngeal cancer patients.
AB  - In a series of 213 incident cases of laryngeal cancer, interviewed 10 years ago
      in the framework of a population-based case-control study, survival has been
      evaluated in relation to tobacco, alcohol consumption and dietary habits. The
      occurrence of other primaries and stage at diagnosis were taken into account as
      possible confounding factors. Heavy tobacco smoking appeared to worsen the
      prognosis in a dose-dependent manner. No effect was apparent for alcohol. The
      consumption of vegetables, citrus fruit, olive oil and orange juice was
      associated with a better prognosis; an opposite association was found for butter
      and milk. A tentative differentiation between dietary patterns showed a 36%
      advantage in survival for those whose dietary habits corresponded to the
      "Mediterranean diet". Our results support the hypothesis that diet may interfere
      with the mechanisms of cancer progression, and suggest that dietary intervention
      could be a means of improving survival in laryngeal cancer patients.

PMID- 8575850
TI  - DNA adducts in urothelial cells: relationship with biomarkers of exposure to
      arylamines and polycyclic aromatic hydrocarbons from tobacco smoke.
AB  - Markers of exposure to polycyclic aromatic hydrocarbons (urinary 1-hydroxypyrene
      glucuronide) and aromatic amines (4-aminobiphenyl-hemoglobin adducts), as well as
      urinary mutagenicity, were measured in 47 healthy smokers and 50 nonsmokers. DNA
      adducts were determined by P32-postlabeling in the exfoliated bladder cells of 39
      healthy subjects. Both 1-hydroxypyrene-glucuronide (1-OHPG) and 4-aminobiphenyl
      adducts (4-ABP-Hb) were associated with smoking habits, but only 4-ABP-Hb adducts
      were associated with consumption of black, air-cured tobacco. The levels of 2 DNA
      adducts (numbers 2 and 4) in urothelial cells were clearly associated with 4-ABP
      Hb adducts, in all subjects and in smokers. Levels of one of these DNA adducts
      (number 2) were also associated with 1-hydroxypyrene-glucuronide in urines, but
      in smokers the association was not statistically significant. Overall, these
      observations constitute further evidence of a role of arylamines in tobacco
      induced bladder cancer.

PMID- 8575851
TI  - Determinants of plasma anti-oxidant vitamin levels in a population at high risk
      for stomach cancer.
AB  - Our objective was to identify the determinants of plasma levels of anti-oxidant
      vitamins which have been linked with decreased risk of cancer and other chronic
      diseases. Correlation analyses were performed between baseline plasma levels of
      ascorbic acid, alpha- and beta-carotenes, cryptoxanthin, lycopene and alpha- and
      gamma-tocopherols and baseline information on dietary and other demographic and
      life-style factors among 1,364 subjects 35-69 years of age, who are participants
      in a chemoprevention trial on pre-cancerous lesions of the stomach in Venezuela.
      Males had lower levels of ascorbic acid, alpha- and beta-carotene and
      cryptoxanthin and higher levels of alpha-tocopherol than females. This finding
      was confirmed in non-smokers and non-drinkers. In females, but not in males, age
      was positively associated with levels of ascorbic acid, cryptoxanthin, alpha- and
      beta-carotene and gamma-tocopherol. Male tobacco users had lower plasma levels of
      ascorbic acid, alpha- and beta-carotene and cryptoxanthin than nonusers, and
      regular alcohol drinkers had a decreased plasma levels of beta-carotene compared
      with non-drinkers. Female tobacco users had lower levels of ascorbic acid and
      cryptoxanthin than non-users, and regular alcohol drinkers had lower levels of
      ascorbic acid and lycopene than non-drinkers. Frequencies of consumption of fresh
      fruits, fruit juice, raw vegetables and plantains showed weak positive
      associations with plasma levels of several vitamins studied in both sexes. Sex,
      age in females, tobacco and alcohol use and dietary consumption affected plasma
      anti-oxidant vitamin levels in this population significantly. These factors may
      influence the effect of anti-oxidant treatment in intervention trials.

PMID- 8575852
TI  - Abundance and subcellular localisation of cyclin D3 in human tumours.
AB  - The D-type cyclins are positive regulators of the G1 phase of the mammalian cell
      cycle. Cyclins D1 or D2 are over-expressed in several types of cancer, transform
      rodent cells in culture and therefore harbor hallmarks of cellular proto
      oncogenes. In contrast, no data on expression of cyclin D3 in tissues and tumours
      are presently available. We have raised monoclonal antibodies (MAbs) specific for
      cyclin D3 and examined abundance and subcellular localisation of this G1 cyclin
      in a series of human cultured cell types and in 180 primary tumours of diverse
      histogenesis. Cyclin D3 localised predominantly in nuclei of normal and tumour
      cells both in culture and in situ, and a pronounced cell-to-cell variation of its
      abundance was reminiscent of cyclins D1 and D2. Immunohistochemical analysis of
      tumour and corresponding normal tissues showed strong aberrant accumulation of
      cyclin D3 in a subset (about 10%) of breast carcinomas, whereas only weak-to
      moderate expression was found in colorectal, head and neck and uterine
      carcinomas, melanomas and soft tissue sarcomas. The specificity of the
      immunohistochemical data was confirmed by immunoblotting analysis of tissue and
      tumour lysates. Our results indicate that over-abundance of cyclin D3 is
      considerably less frequent than that of cyclin D1, yet we identify subsets of
      breast tumours, and potentially lymphomas, as candidate tumour types with
      elevated cyclin D3 expression.

PMID- 8575853
TI  - Meat, fat and risk of breast cancer: a case-control study from Uruguay.
AB  - To examine whether meat intake modifies breast-cancer risk, a case-control study
      was conducted in Uruguay. Dietary patterns were assessed in detail (for cases,
      before diagnosis or symptoms occurred) using a food frequency questionnaire
      involving 64 food items, which allowed total energy intake to be calculated.
      Nutrient residuals were calculated through regression analysis. After adjustment
      for potential confounders (which included family history of breast cancer,
      menopausal status, body-mass index, total energy and total alcohol intake), an
      increased risk associated with consumption of total meat intake, red meat intake,
      total fat and saturated fat intake was observed. The strongest effect was
      observed for red meat intake (OR 4.2, 95% CL 2.3-7.7) for consumption in the
      upper quartile, after controlling for protein and fat intake. This suggests an
      independent effect for meat. Since experimental studies have shown a strong
      effect of heterocyclic amines in rat mammary carcinogenesis, further studies
      should be performed in human epidemiology, perhaps using biomarkers of
      heterocyclic amine exposure.

PMID- 8575854
TI  - Transforming growth factor-beta-mediated autocrine growth regulation of gliomas
      as detected with phosphorothioate antisense oligonucleotides.
AB  - Transforming growth factors-beta 1 and -beta 2 (TGF-beta 1 and -beta 2) are
      important growth-regulatory proteins for astroglial neoplasms. We analyzed their
      role in tumor-cell proliferation in 12 glioma cell lines, employing
      phosphorothioate antisense oligodeoxynucleotides (S-ODNs, 14 mer), specifically
      targeted against the coding sequences of TGF-beta 1-mRNA and TGF-beta 2-mRNA. TGF
      beta 1-S-ODNs inhibited cell proliferation in 5 of 12 gliomas, whereas TGF-beta 2
      S-ODNs reduced the cell proliferation in all glioma cell lines, compared to
      nonsense-S-ODN-treated and S-ODN-untreated cells as controls. The efficacy and
      specificity of antisense effects was validated by Northern-blot analysis and
      determination of protein concentrations in culture supernatants (ELISA).
      Exogenous hrTGF-beta 1 either stimulated or inhibited the cell lines, whereas
      pnTGF-beta 2 stimulated the proliferation of most glioma cells. Blocking the
      extracellular pathway of TGF-beta by neutralizing antibodies only slightly
      inhibited those cell lines, which were markedly stimulated by TGF-betas. As the
      effects of TGF-beta 2-S-ODNs were much stronger than those of TGF-beta
      neutralizing antibodies, we postulate that the endogenously produced TGF-beta 2
      control glioma-cell proliferation, in part by an intracellular loop.

PMID- 8575855
TI  - Malignant transformation of HPV 16-immortalized human endocervical cells by
      cigarette smoke condensate and characterization of multistage carcinogenesis.
AB  - A number of epidemiological studies indicate that cigarette smokers are at
      increased risk of developing cervical cancer. However, convincing biological
      evidence is lacking. This report examines the biological and cellular role of
      human papillomavirus (HPV) type 16 and cigarette smoke in multistage cervical
      carcinogenesis. Two lines of HPV 16-immortalized human endocervical cells (HEN-16
      and HEN-16-2) generated from primary cells (HEN) were treated with cigarette
      smoke condensate (CSC). CSC-treated, but not untreated, HEN-16 and HEN-16-2
      formed tumors that were invasive squamous cell carcinomas in nude mice. The
      tumors were used to initiate 2 tumor lines of cells (HEN-16T and HEN-16-2T,
      respectively). Cells of both tumor lines, compared with HEN, HEN-16 and HEN-16-2,
      featured: (a) tumorigenicity, (b) distinct morphologies in monolayer and
      organotypic (raft) cultures, (c) faster growth in serum plus high calcium levels
      after immortalization and after transformation, (d) higher saturation density and
      (e) anchorage-independent growth. Our results provide unique direct in vitro
      evidence that cigarette smoke causes cancer in HPV-containing cervices.

PMID- 8575856
TI  - Resistance to retinoic acid and altered cytokeratin expression of human
      papillomavirus type 16-immortalized endocervical cells after tumorigenesis.
AB  - Human papillomaviruses (HPVs) and cigarette smoking are epidemiologically
      associated with cervical cancer. We recently found that HEN-16 and HEN-16-2 HPV
      type 16-immortalized endocervical cells form tumors after treatment with
      cigarette smoke condensate and derived 2 tumor cell line cultures, HEN-16T and
      HEN-16-2T, respectively. Here, we examine the molecular pathologic effect of
      tumorigenesis. HEN-16T and HEN-16-2T exhibit unchanged status and expression of
      integrated HPV 16 DNA. However, the expression of the cytokeratin CK7 and CK13
      endocervical cell markers is more homogeneous in monolayer and organotypic raft
      cultures after tumorigenesis. For the effect of retinoic acid on monolayers for
      growth inhibition, HEN-16T were significantly less sensitive than the normal and
      immortalized non-tumorigenic cells. HEN-16-2T were completely resistant.
      Moreover, the rafts from both tumorigenic cell line cultures were resistant to
      retinoic acid and continued to display thick rafts and homogeneous severe
      dysplasia/carcinoma in situ. In contrast, the non-malignant HEN-16 and HEN-16-2
      rafts were thinner, and treatment with retinoic acid blocked the formation of
      severe dysplasia, reconstructing an epithelium resembling that of the normal
      endocervix. Our results support the significance of non-viral factors in the
      mechanism by which cigarette smoking induces tumorigenesis in the late stages of
      HPV-initiated progression to cervical cancer. Importantly, our data indicate that
      the sensitivity to retinoic acid of the HPV-containing endocervical cells is lost
      following tumorigenesis in vitro and possibly in women.

PMID- 8575857
TI  - SDZ 281-977: a modified partial structure of lavendustin A that exerts potent and
      selective antiproliferative activities in vitro and in vivo.
AB  - The chemical derivatization of biologically active microbial metabolites
      continues to be a promising approach to the identification of new drugs. We
      recently synthesized the novel antiproliferative compound SDZ 281-977, 5-[2-(2,5
      dimethoxy-phenyl)ethyl]-2-hydroxy-benzoic acid methylester, a derivative of the
      EGF receptor tyrosine kinase inhibitor lavendustin A. Here we report on our
      studies of the anticancer efficacy and the mode of action of SDZ 281-977. The
      growth of both the human pancreatic tumor cells MIA PaCa-2 and the human vulvar
      carcinoma cells A431 was inhibited in the low micromolar range. Tumors from these
      cells were induced in nude mice and were shown to respond to orally or
      intravenously administered SDZ 281-977. In contrast, no antitumor effect was
      detected in rats bearing dimethylbenzanthracene-induced mammary tumors. Studies
      in mice indicated that SDZ 281-977 was neither immunosuppressive nor
      hematosuppressive at doses effectively inhibiting tumor growth. Surprisingly, the
      mode of action of SDZ 281-977 apparently does not involve inhibition of EGF
      receptor tryosine kinase, because, in contrast to lavendustin A, SDZ 281-977
      failed to inhibit this enzyme in a cell-free assay. The mechanism of the
      antiproliferative effect can be explained on a cellular level by the ability of
      the compound to arrest cells in mitosis. SDZ 281-977 is thus the first example of
      an antimitotic agent derived from the potent tyrosine kinase inhibitor
      lavendustin A. The therapeutic potential of SDZ 281-977 is enhanced by the fact
      that it is not subject to multidrug resistance, because tumor cells expressing
      the multidrug resistance phenotype were as sensitive to SDZ 281-977 as their
      nonresistant counterparts. In conclusion, SDZ 281-977 represents a novel
      lavendustin A derivative with potent antiproliferative properties in vitro and in
      vivo that may be explained on the basis of its antimitotic effects. SDZ 281-977
      may be a candidate drug for the treatment of selected cancers, including those
      expressing the multidrug resistance phenotype.

PMID- 8575858
TI  - Timing of cancer chemotherapy based on circadian variations in tumor tissue blood
      flow.
AB  - Blood flows of normal tissues (subcutis, liver, kidney cortex, bone marrow) and
      tumor tissues (SLC) were measured during a daytime period (3-9 HALO) and a
      nighttime period (15-21 HALO) by the hydrogen clearance technique. Rats were
      subjected to an artificial light-dark cycle with light from 7 A.M. to 7 P.M. In
      all normal tissues, there were no significant differences between average tissue
      blood flows in 2 different time zones, while tumor tissue blood flow increased
      significantly in the nighttime. Based on this functional characteristic of tumor
      microcirculation, anti-tumor effects were compared between a group in which ADM
      was administered at 4 HALO and a group in which it was administered at 16 HALO.
      The therapeutic effect of ADM on rats administered at 16 HALO was significantly
      greater, particularly in large tumors, than that on rats administered at 4 HALO.
      The main reason for this therapeutic improvement may be due to the selective
      increase in delivery of anti-cancer drugs to tumor tissues brought about by a
      circadian increase in tumor tissue blood flow.

PMID- 8575859
TI  - Sequential emergence of MRP- and MDR1-gene over-expression as well as MDR1-gene
      translocation in homoharringtonine-selected K562 human leukemia cell lines.
AB  - To investigate the mechanism of resistance to an antineoplastic natural product
      homoharringtonine (HHT) in leukemic cells, we have established 5 sub-lines of
      human myeloid leukemia K562 cells, designated as K-H30, K-H100, K-H200, K-H300
      and K-H400, which showed progressive resistance to different concentrations of
      HHT. These sub-lines were cross-resistant to daunorubicin, vincristine, etoposide
      and mitoxantrone, but not to melphalan. Immunofluorescence with monoclonal anti
      Pgp antibody MRK16 and Northern-blot analysis demonstrated that resistance to HHT
      is related to the sequential emergence of MRP- and MDR1-gene over-expression. In
      the low-level-resistant K-H30 sub-line, the MDR1 gene was not over-expressed, but
      the MRP gene was over-expressed 2.1-fold. In the intermediate-level-resistant K
      H100 and K-H200 sublines, both the MRP and the MDR1 genes were over-expressed.
      However, in the high-level-resistant K-H300 and K-H400 sublines, MDR1-gene over
      expression predominated (20- and 21-fold respectively). On the other hand, GST pi
      gene expression was decreased in all 5 sub-lines. Southern-blot analysis revealed
      no MRP-gene amplification in any of the 5 sub-lines, whereas the MDR1 gene was
      amplified in the high-level-resistant K-H300 and K-H400 sub-lines. The most
      interesting observation is a homogeneously staining region (HSR) found in
      chromosome 2 of the K-H300 and K-H400 sub-lines. Chromosome painting and in situ
      hybridization demonstrated that this HSR was translocated from chromosome 7 and
      consisted of the amplified MDR1 gene, suggesting that there is a relationship
      between MDR1-gene, translocation and MDR1-gene amplification.

PMID- 8575860
TI  - Characterization of p53 gene mutations in esophageal squamous cell carcinoma cell
      lines: increased frequency and different spectrum of mutations from primary
      tumors.
AB  - We screened 29 human esophageal squamous cell carcinoma (ESC) cell lines for
      mutations of the p53 gene through all coding exons and exon-intron junctions.
      Mutations were found in 22 cell lines (76%), consisting of 20 single-base
      substitutions, 2 small deletions and 1 single-base insertion. Out of 20 single
      base substitution, 5 were located at the exon-intron junctions and mRNAs with
      abnormal splicing were detected by RT-PCR in 4 of them. A G:C to T:A
      transversion, which occurred rather frequently in resected tumors of ESC, was
      observed in only 1 cell line, and, instead, frequent transitions at CpG sites
      were detected. We also examined 65 fresh tumor materials, from all of which we
      tried to establish cell lines, and detected mutations in 26 samples (40%).
      Compared with the results in these fresh tumor materials, the mutation incidence
      in cell lines was significantly high and the mutation spectrum was also
      different. From these 65 tumors, 10 cell lines were established, including 3 cell
      lines from 26 tumors with p53 mutations and 7 cell lines from 39 without
      mutations, which indicates that there was no significant correlation between the
      status of the p53 gene in each fresh tumor and its establishment as a cell line.
      In 7 cell lines established from mutation-free tumors, newly acquired mutations
      were detected in 5, which suggests that mutations might occur during the process
      of establishing cell lines.

PMID- 8575861
TI  - Pulmonary metastases neutralization and tumor rejection by in vivo administration
      of beta glucan and bispecific antibody.
AB  - Bispecific antibody (BsAb) with specificity for tumor cell surface antigen and
      the CD3 molecule on T cells can redirect activated T cells to lyse tumor cells.
      Since the ex vivo expansion and activation of T cells is impractical and
      ineffective for treating established tumors, we tested whether the immune
      stimulant beta glucan could in situ-activate T cells, which could secondarily be
      retargeted with BsAbs to lyse tumor cells. To test for tumor neutralization,
      C3H/HeN mice were injected i.v. with Cl-62 melanoma cells and immediately treated
      with i.p. beta glucan and/or anti-CD3 (500A2) x anti-p97 (96.5) F(ab')2 BsAb i.v.
      Pulmonary metastases were counted 14 days later. To test for tumor rejection and
      survival in a solid tumor model, mice were injected s.c. and i.p. with Cl-62
      cells and 7 days later administered beta glucan i.p. and/or F(ab')2 BsAb i.v. In
      the neutralization model, there was a significant reduction in the number of
      metastases in the beta glucan + BsAb group, as compared with controls, and with
      beta glucan alone. In the established tumor model, beta glucan + BsAb reduced the
      incidence of s.c. tumors as compared with control, with BsAb alone and with beta
      glucan alone. It also prolonged survival of tumor-bearing mice compared with
      control, BsAb alone and beta glucan alone. We conclude that T cells can be
      activated in vivo by beta glucan and retargeted with F(ab')2 BsAb.

PMID- 8575862
TI  - Immunochemical identification of novel high-molecular-weight protein isoforms of
      the adenomatous polyposis coli (APC) gene.
AB  - Mapping analyses of monoclonal antibodies (MAbs) directed against the amino
      terminus of the adenomatous polyposis coli (APC) gene product revealed that
      epitopes recognized by the MAbs FE9, CF11 and AC4 constitute different peptide
      sequences encoded by the APC exons 1, 2 and 3, respectively. The protein pattern
      detected with these specificity-defined immunoreagents, however, differed
      depending on the particular antibody used on Western blots of cellular urea
      extracts. APC exon 15-positive "classic" p300apc polypeptide chains were
      identified by the MAb FE9, MAb CF11 and the C-terminus-specific MAb IE1, but only
      weak signals were obtained with the AC4 MAb, which defines an exon 3-encoded
      epitope. In contrast with this immunoreactivity, 2 novel high m.w. products of
      approx. 150/160 and 200 kDa were exclusively recognized by the AC4 MAb, which was
      shown to bind to the APC exon 3-encoded peptide sequence SRESTGYL. A molecular
      form of some 400 kDa was identified to represent a disulfide-bound oligomer of
      the p150/160apc molecules. The novel APC-related molecules did not contain exon 1
      and exon 15-encoded epitopes, as confirmed with the help of the FE9 and IE1
      MAbs, respectively. This observation was corroborated by the fact that these
      novel proteins were not truncated in a collection of familial adenomatous
      polyposis patients with stop mutations in exon 15. We conclude, that APC MAb AC4
      reactive p150/160 and p200 polypeptide chains represent novel genuine products of
      the APC gene devoid of exon 1- and exon 15-encoded protein interaction domains.

PMID- 8575863
TI  - Effect of combination of suboptimal concentrations of P-glycoprotein blockers on
      the proliferation of MDR1 gene expressing cells.
AB  - Pharmacologically active in vivo doses of P-glycoprotein (Pgp) blockers,
      specifically verapamil, Cremophor EL and PSC833 cause toxicity in addition to
      that from the concomitantly used cancer chemotherapeutic drugs. It was shown
      before that these blockers cause different types of toxicities in vivo. We found
      that these 3 chemically distinct Pgp blockers exert different biophysical effects
      on the membranes of L1210 MDR cells. They also affect the general metabolism of
      these cells differently, but all block affinity labeling of Pgp. We could also
      show that the combination of suboptimal doses of these blockers can restore the
      uptake of the Pgp substrate rhodamine 123 into L1210MDR, 3T3MDR and KB-VI cells
      and can reduce the survival rate of these cells when treated in combination with
      daunorubicin. Our results suggest that the combination of suboptimal doses of
      these Pgp blockers may be advantageous in clinical practice.

PMID- 8575864
TI  - The evolution of FDA policy on silicone breast implants: a case study of
      politics, bureaucracy, and business in the process of decision-making.
AB  - The central issue facing federal regulation of breast implants is that while such
      devices are not functionally necessary or needed for survival, the side effects
      may be harmful and have not been proven unharmful. The Medical Device Amendments
      of 1976 appear to require such evidence prior to the FDA permitting the
      unrestricted marketing of these devices. However, only recently have such
      requirements been imposed by the FDA. The author examines the FDA's decision
      making process, particularly as applied to silicone breast implants, and the
      factors that appears to have affected such decisions. In pursuing this study, the
      activities of a number of interest-group actors, as well as congressional
      responses and the role of federal bureaucratic actors, were examined. In 1992,
      the FDA established a regulatory protocol that effectively withdrew most silicone
      breast implants from the market for the purpose of breast augmentation and allows
      for the monitoring of the impact of new implants on women's health. This increase
      concern for determining the safety of breast implants is due to a number of
      factors, which are examined in this article.

PMID- 8575865
TI  - Well-healed: inside lobbying for health care reform, Part II. Center for Public
      Integrity.
AB  - The Center for Public Integrity conducted a year-long investigation of the
      decision-making processes of the U.S. government during its work on health care
      reform. The results suggest that health care reform has become the most heavily
      lobbied legislative initiative in recent U.S. history. In 1993 and 1994, hundreds
      of special interests spent over $100 million to influence the outcome of this
      public policy issue. In Part II, the authors describe some of these special
      interests, including the insurance industry, both the largest companies and those
      that make up the Health Insurance Association of America; doctors, hospitals, and
      other health care providers; the pharmaceutical industry; businesses of all
      sizes; and the tobacco industry.

PMID- 8575866
TI  - Playing chicken with people: the occupational safety and health consequences of
      throughput uber alles.
AB  - The political-economic and legal analysis of regulation in this article argues
      that the speed of work on disassembly lines in poultry processing plants, the
      fastest growing factory employment in the United States, is de facto regulated
      not by the Occupational Safety and Health Administration, the agency charged with
      protecting workers, but, perversely, by the U.S. Department of Agriculture. In
      arrogating to itself the power to set line speeds in connection with its
      inspection of processed carcasses, the Department of Agriculture has one-sidedly
      promoted chicken oligopolies' interests by accommodating their drive to produce
      as much product as quickly and cheaply as possible (throughput uber alles) and
      especially without regard to the incidence of repetitive stress disorders
      associated with high-speed machine-paced manual production. In contrast, the
      Occupational Safety and Health Administration has failed either to assert its
      statutory authority over this vital determinant of workers' well-being or to
      persuade any administrative or judicial tribunal that it possesses such
      authority. Consequently, the article concludes, the health and safety of 200,000
      low-paid and largely unorganized, female, and non-white workers continue to be
      held hostage to the self-valorization needs of capital and the state's cheap food
      policy.

PMID- 8575867
TI  - The origin and development of the asbestos Threshold Limit Value: scientific
      indifference and corporate influence.
AB  - Several recent articles have critiqued the process employed by the American
      Conference of Governmental Industrial Hygienists in determining Threshold Limit
      Values. Criticisms have included inadequate data collection, inadequate research,
      excessive corporate influence, and slow response to informational changes. In
      this article, the authors address the historical development of the American
      Conference of Governmental Industrial Hygienists' asbestos exposure guideline.
      They demonstrate that the proposed guideline was known to be inadequate when it
      was first proposed, was severely criticized between 1946 and 1968, but
      nonetheless was promulgated annually and remained unchanged 1971.

PMID- 8575868
TI  - The World Bank, pensions, and income (in)security in the global south.
AB  - The authors describe and analyze recent reductions and reorganizations of public
      pension programs in Latin America, as well as trends in pensions in the global
      South more broadly. They consider the role of the World Bank in the current
      pension "reform" process and situate the Bank's policies in the context of
      privatization, reduction of social budgets, and other aspects of structural
      adjustment. Chilean pension changes are analyzed in particular, showing that even
      by the Bank's criteria, the reforms have not been successful. The authors then
      discuss pension changes in China, where the World Bank is also deeply involved.
      The article concludes with the consideration of a number of arguments about
      pensions and support mechanisms in later life--including family support and means
      tested welfarism--and argues in favor of global policy approaches, such as
      globally funded pensions and full access by older persons to productive and
      remunerated labor.

PMID- 8575870
TI  - ICN task force concerned about HIV/AIDS work risks.

PMID- 8575869
TI  - Health and social policies in the new South Africa.
AB  - South Africa's first democratic government is today confronted with the challenge
      of recasting apartheid social and health policies, transforming a moribund
      bureaucracy's mode of governance, and restructuring a variety of public and
      private institutions, including the national Department of Health. In the attempt
      to redress racial, gender, and class inequities, enormous barriers confront
      health policy analysts and planners, progressive politicians, and activists
      within civil society who work in the field of health. This article sets the broad
      social policy context for the emerging strategies, documents some of the
      continuing inequities in the health sector, and recounts some recent experiences
      in one of the nine provinces (KwaZulu-Natal). to illustrate the difficulties and
      potentials that change of this magnitude presents under the prevailing conditions
      of neoliberal politics and economics.

PMID- 8575871
TI  - Combating Ebola: model of international collaboration.

PMID- 8575872
TI  - Long-term HIV survivors in the spotlight.

PMID- 8575873
TI  - Cultural differences in Canadian-Chinese nursing.
AB  - The Schools of Nursing of Tianjin Medical College and the University of Ottawa
      have been partners in a Canadian-Chinese linkage project funded by the Canadian
      International Development Agency (CIDA) and the Chinese Government since 1989, at
      teh instigation of Canadian faculty member Nancy Johnson who saw the need for
      academic support for the Chinese nursing community.

PMID- 8575874
TI  - Nursing's values from a Confucian perspective.
AB  - Confucius' sayings-derived from his 450 recorded brief conversations and
      observations-colourfully expound such basic virtues as a child's duty toward
      his/her parents, love between brothers, devotion to family tradition, reliability
      in friendships, loyalty to superiors and justice to all men. How five major
      values of Confucian beliefs fit into nursing practices are elaborated below.

PMID- 8575875
TI  - Building nursing leaders in Latin America.
AB  - For over 40 years the W.K. Kellogg Foundation of the US has helped strengthen
      nursing in Latin America through its support of projects to meet the profession's
      educational needs.

PMID- 8575876
TI  - International regulation today.
AB  - How much, what kind and who should control professional regulation and the
      questions being debated in many countries. To understand the nature, implications
      and impact of the regulatory processes used in their country, nurses must assist
      in: 1) developing the regulatory controls that affect professional education,
      practice and research; and 2) ensuring that nursing is a major player in the
      administrative and monitoring processes used to control nursing.

PMID- 8575877
TI  - How to prevent burnout.
AB  - Burnout is a major problem affecting health professionals, particularly those
      caring for chronic, incurable and dying patients. Interestingly, some of the
      factors that help individuals to recover from burnout are the same ones that help
      prevent burnout: new work situations that provide autonomy, organizational
      support and interesting work.

PMID- 8575878
TI  - The nuclear matrix: a structural milieu for genomic function.
AB  - While significant progress has been made in elucidating molecular properties of
      specific genes and their regulation, our understanding of how the whole genome is
      coordinated has lagged behind. To understand how the genome functions as a
      coordinated whole, we must understand how the nucleus is put together and
      functions as a whole. An important step in that direction occurred with the
      isolation and characterization of the nuclear matrix. Aside from the plethora of
      functional properties associated with these isolated nuclear structures, they
      have enabled the first direct examination and molecular cloning of specific
      nuclear matrix proteins. The isolated nuclear matrix can be used for providing an
      in vitro model for understanding nuclear matrix organization in whole cells.
      Recent development of high-resolution and three-dimensional approaches for
      visualizing domains of genomic organization and function in situ has provided
      corroborative evidence for the nuclear matrix as the site of organization for
      replication, transcription, and post-transcriptional processing. As more is
      learned about these in situ functional sites, appropriate experiments could be
      designed to test molecular mechanisms with the in vitro nuclear matrix systems.
      This is illustrated in this chapter by the studies of nuclear matrix-associated
      DNA replication which have evolved from biochemical studies of in vitro nuclear
      matrix systems toward three-dimensional computer image analysis of replication
      sites for individual genes.

PMID- 8575879
TI  - The structural basis of nuclear function.
AB  - Most models for transcription and replication involve polymerases that track
      along the template. We review here experiments that suggest an alternative in
      which polymerization occurs as the template slides past a polymerase fixed to a
      large structure in the eukaryotic nucleus--a "factory" attached to a
      nucleoskeleton. This means that higher-order structure dictates how and when DNA
      is replicated or transcribed.

PMID- 8575880
TI  - Nuclear domains and the nuclear matrix.
AB  - This overview describes the spatial distribution of several enzymatic machineries
      and functions in the interphase nucleus. Three general observations can be made.
      First, many components of the different nuclear machineries are distributed in
      the nucleus in a characteristic way for each component. They are often found
      concentrated in specific domains. Second, nuclear machineries for the synthesis
      and processing of RNA and DNA are associated with an insoluble nuclear structure,
      called nuclear matrix. Evidently, handling of DNA and RNA is done by immobilized
      enzyme systems. Finally, the nucleus seems to be divided in two major
      compartments. One is occupied by compact chromosomes, the other compartment is
      the space between the chromosomes. In the latter, transcription takes place at
      the surface of chromosomal domains and it houses the splicing machinery. The
      relevance of nuclear organization for efficient gene expression is discussed.

PMID- 8575881
TI  - The nuclear matrix and the regulation of chromatin organization and function.
AB  - Nuclear DNA is organized into loop domains, with the base of the loop being bound
      to the nuclear matrix. Loops with transcriptionally active and/or potentially
      active genes have a DNase I-sensitive chromatin structure, while repressed
      chromatin loops have a condensed configuration that is essentially invisible to
      the transcription machinery. Core histone acetylation and torsional stress appear
      to be responsible for the generation and/or maintenance of the open potentially
      active chromatin loops. The transcriptionally active region of the loop makes
      several dynamic attachments with the nuclear matrix and is associated with core
      histones that are dynamically acetylated. Histone acetyltransferase and
      deacetylase, which catalyze this rapid acetylation and deacetylation, are bound
      to the nuclear matrix. Several transcription factors are components of the
      nuclear matrix. Histone acetyltransferase, deacetylase, and transcription factors
      may contribute to the dynamic attachment of the active chromatin domains with the
      nuclear matrix at sites of ongoing transcription.

PMID- 8575882
TI  - Contributions of nuclear architecture to transcriptional control.
AB  - Three parameters of nuclear structure contribute to transcriptional control. The
      linear representation of promoter elements provides competency for physiological
      responsiveness within the contexts of development as well as cycle- and phenotype
      dependent regulation. Chromatin structure and nucleosome organization reduce
      distances between independent regulatory elements providing a basis for
      integrating components of transcriptional control. The nuclear matrix supports
      gene expression by imposing physical constraints on chromatin related to three
      dimensional genomic organization. In addition, the nuclear matrix facilitates
      gene localization as well as the concentration and targeting of transcription
      factors. Several lines of evidence are presented that are consistent with
      involvement of multiple levels of nuclear architecture in cell growth and tissue
      specific gene expression during differentiation. Growth factor and steroid
      hormone responsive modifications in chromatin structure, nucleosome organization,
      and the nuclear matrix that influence transcription of the cell cycle-regulated
      histone gene and the bone tissue-specific osteocalcin gene during progressive
      expression of the osteoblast phenotype are considered.

PMID- 8575883
TI  - Chromatin domains and prediction of MAR sequences.
AB  - Polynuceosomes are constrained into loops or domains and are insulated from the
      effects of chromatin structure and torsional strain from flanking domains by the
      cross-complexation of matrix-attached regions (MARs) and matrix proteins. MARs or
      SARs have an average size of 500 bp, are spaced about every 30 kb, and are
      control elements maintaining independent realms of gene activity. A fraction of
      MARs may cohabit with core origin replication (ORIs) and another fraction might
      cohabit with transcriptional enhancers. DNA replication, transcription, repair,
      splicing, and recombination seem to take place on the nuclear matrix. Classical
      AT-rich MARs have been proposed to anchor the core enhancers and core origins
      complexed with low abundancy transcription factors to the nuclear matrix via the
      cooperative binding to MARs of abundant classical matrix proteins (topoisomerase
      II, histone H1, lamins, SP120, ARBP, SATB1); this creates a unique nuclear
      microenvironment rich in regulatory proteins able to sustain transcription,
      replication, repair, and recombination. Theoretical searches and experimental
      data strongly support a model of activation of MARs and ORIs by transcription
      factors. A set of 21 characteristics are deduced or proposed for MAR/ORI
      sequences including their enrichment in inverted repeats, AT tracts, DNA
      unwinding elements, replication initiator protein sites, homooligonucleotide
      repeats (i.e., AAA, TTT, CCC), curved DNA, DNase I-hypersensitive sites,
      nucleosome-free stretches, polypurine stretches, and motifs with a potential for
      left-handed and triplex structures. We are establishing Banks of ORI and MAR
      sequences and have undertaken a large project of sequencing a large number of
      MARs in an effort to determine classes of DNA sequences in these regulatory
      elements and to understand their role at the origins of replication and
      transcriptional enhancers.

PMID- 8575884
TI  - Scaffold/matrix-attached regions: structural properties creating
      transcriptionally active loci.
AB  - The expression characteristics of the human interferon-beta gene, as part of a
      long stretch of genomic DNA, led to the discovery of the putative domain
      bordering elements. The chromatin structure of these elements and their
      surroundings was determined during the process of gene activation and correlated
      with their postulated functions. It is shown that these "scaffold-attached
      regions" (S/MAR elements) have some characteristics in common with and others
      distinct from enhancers with which they cooperate in various ways. Our model of
      S/MAR function will focus on their properties of mediating topological changes
      within the respective domain.

PMID- 8575886
TI  - The nuclear matrix and virus function.
AB  - Replication of the small DNA tumor virus, simian virus 40 (SV40), is largely
      dependent on host cell functions, because SV40, in addition to virion proteins,
      codes only for a few regulatory proteins, the most important one being the SV40
      large tumor antigen (T-antigen). This renders SV40 an excellent tool for studying
      complex cellular and viral processes. In this review we summarize and discuss
      data providing evidence for virtually all major viral processes during the life
      cycle of SV40 from viral DNA replication to virion formation, being performed at
      or within structural systems of the nucleus, in particular the chromatin and the
      nuclear matrix. These data further support the concept that viral replication in
      the nucleus is structurally organized and demonstrate that viruses are excellent
      tools for analyzing the underlying cellular processes. The analysis of viral
      replication at nuclear structures might also provide a means for specifically
      interfering with viral processes without interfering with the corresponding
      cellular functions.

PMID- 8575885
TI  - Origins of replication and the nuclear matrix: the DHFR domain as a paradigm.
AB  - The eukaryotic genome appears to be organized in a loopwise fashion by periodic
      attachment to the nuclear matrix. The proposal that a chromatin loop corresponds
      to a functional domain has stirred interest in the properties of the DNA
      sequences at the bases of these loops, the matrix-attached regions (MARs).
      Evidence has been presented suggesting that certain MARs act as boundary elements
      isolating domains from their chromosomal context. MARs have also been found in
      the vicinity of promoters and enhancers and they could act by displacing these
      cis-regulatory elements into the proper nuclear subcompartment. Attachment to the
      matrix might also play a role in DNA replication. A large body of evidence
      indicates that replication occurs on the nuclear matrix. This implies that any
      DNA sequence will be attached to the matrix at a certain time during the cell
      cycle. This transient mode of attachment contrasts with the proposed permanent
      attachment of origins of DNA replication with the nuclear matrix. While some data
      exist that support this suggestion, the current lack of understanding of the
      mammalian replication origin precludes definitive conclusions regarding the role
      of MARs in the initiation process.

PMID- 8575887
TI  - The nuclear matrix as a site of anticancer drug action.
AB  - Many nuclear functions, including the organization of the chromatin within the
      nucleus, depend upon the presence of a nuclear matrix. Nuclear matrix proteins
      are involved in the formation of chromatin loops, control of DNA supercoiling,
      and regulation and coordination of transcriptional and replicational activities
      within individual loops. Various structural and functional components of the
      nuclear matrix represent potential targets for anticancer agents. Alkylating
      agents and ionizing radiation interact preferentially with nuclear matrix
      proteins and matrix-associated DNA. Other chemotherapeutic agents, such as
      fludarabine phosphate and topoisomerase II-active drugs, interact specifically
      with matrix-associated enzymes, such as DNA primase and the DNA topoisomerase II
      alpha isozyme. The interactions of these agents at the level of the nuclear
      matrix may compromise multiple nuclear functions and be relevant to their
      antitumor activities.

PMID- 8575888
TI  - The architectural organization of nuclear metabolism.
AB  - Nucleic acid metabolism is structurally organized in the nucleus. DNA replication
      and transcription have been localized to particular nuclear domains. Additional
      domains have been identified by their morphology or by their composition; for
      example, by their high concentration of factors involved in RNA splicing. The
      domain organization of the nucleus is maintained by the nuclear matrix, a
      nonchromatin nuclear scaffolding that holds most nuclear RNA and organizes
      chromatin into loops. The nuclear matrix is built on a network of highly branched
      core filaments that have an average diameter of 10 nm. Many of the intermediates
      and the regulatory and catalytic factors of nucleic acid metabolism are retained
      in nuclear matrix preparations, suggesting that nucleic acid synthesis and
      processing are structure-bound processes in cells. Tissue-specific and malignancy
      induced variations in nuclear structure and metabolism may result from altered
      matrix architecture and composition.

PMID- 8575889
TI  - Multifunctional proteins in Tetrahymena: 14-nm filament protein/citrate synthase
      and translation elongation factor-1 alpha.
AB  - One gene encoding a protein has been shown to have two entirely different
      functions. Such a phenomenon, which has been called "gene sharing," was first
      known in crystallins. We found two multifunctional proteins in the ciliated
      protozoan Tetrahymena: 14-nm filament protein and protein translation elongation
      factor 1-alpha (EF-1 alpha). The 14-nm filament protein has dual functions as a
      citrate synthase in mitochondria and as a cytoskeletal protein in cytoplasm. In
      cytoplasm, the 14-nm filament protein was involved in oral morphogenesis and in
      pronuclear behavior during conjugation. The observation that Tetrahymena
      intramitochondrial filamentous inclusions contain the 14-nm filament protein and
      that the citrate synthase activity of the 14-nm filament protein is decreased by
      polymerization and increased by depolymerization, suggests a possible modulating
      mechanism of citrate synthase activity by monomer-polymer conversion in
      mitochondria in situ. The EF-1 alpha functions as an F-actin-bundling protein and
      a 14-nm filament-associated protein as well as an elongation factor in protein
      synthesis. The F-actin-bundling activity of EF-1 alpha was regulated by Ca2+ and
      calmodulin. Here we review the properties and functions of two multifunctional
      proteins in Tetrahymena.

PMID- 8575890
TI  - Developmental failure in preimplantation human conceptuses.
AB  - The majority of human conceptuses fertilized normally in vitro fail to establish
      a pregnancy following their replacement in utero. However, since conceptuses are
      usually transferred after only one or two cell divisions, their developmental
      outcome is not known. It has been found that a significant number of human
      oocytes which can be fertilized carry chromosomal abnormalities, even in the
      absence of ovarian stimulation. After fertilization, preimplantation-stage
      conceptuses developing in vitro display a high incidence of cellular
      abnormalities. Similar disruptions of cellular organization have also been noted
      in conceptuses fertilized in vivo. Thus, developmental abnormalities and the
      demise of the conceptus prior to the stage of implantation may stem from the poor
      quality of the oocyte. The conditions encountered in vitro have also been
      proposed to cause or contribute to the early demise of human conceptuses.

PMID- 8575891
TI  - G-protein-coupled receptors in insect cells.
AB  - The main classes of transmembrane signaling receptor proteins are well conserved
      during evolution and are encountered in vertebrates as well as in invertebrates.
      All members of the G-protein-coupled receptor superfamily share a number of basic
      structural and functional characteristics. In both insects and mammals, this
      receptor class is involved in the perception and transduction of many important
      extracellular signals, including a great deal of paracrine, endocrine, and
      neuronal messengers and visual, olfactory and gustatory stimuli. Therefore, most
      of the receptor subclasses appear to have originated several hundred million
      years ago, before the divergence of the major animal Phyla took place.
      Nevertheless, many insect-specific molecular interactions are encountered and
      these could become interesting tools for future applications, e.g., in insect
      pest control. Insect cell lines are well suited for large-scale expression and
      characterization of cloned receptor genes. Furthermore, novel methods for the
      production of stably transformed insect cells may form a major breakthrough for
      insect signal transduction research.

PMID- 8575892
TI  - Microtubules and microtubule motors: mechanisms of regulation.
AB  - Microtubule-based motility is precisely regulated, and the targets of regulation
      may be the motor proteins, the microtubules, or both components of this
      intricately controlled system. Regulation of microtubule behavior can be mediated
      by cell cycle-dependent changes in centrosomal microtubule nucleating ability and
      by cell-specific, microtubule-associated proteins (MAPs). Changes in microtubule
      organization and dynamics have been correlated with changes in phosphorylation.
      Regulation of motor proteins may be required both to initiate movement and to
      dictate its direction. Axonemal and cytoplasmic dyneins as well as kinesin can be
      phosphorylated and this modification may affect the motor activities of these
      enzymes or their ability to interact with organelles. A more complete
      understanding of how motors can be modulated by phosphorylation, either of the
      motor proteins or of other associated substrates, will be necessary in order to
      understand how bidirectional transport is regulated.

PMID- 8575893
TI  - Some characteristics of neoplastic cell transformation in transgenic mice.
AB  - The role of the expression of different cellular genes and viral oncogenes in
      malignant cell transformation is discussed. We pay special attention to the role
      of the genes for growth factors and their receptors and homeobox genes in
      oncogenesis. Based on both the literature and our own data, specific features of
      tumors developed in transgenic mice are discussed. All of these data are used to
      analyze current theories of multistep oncogenesis and the stochastic component in
      this process. We suggest that all known evidence about the mechanisms of
      oncogenesis be used in studying the problem at various structural and functional
      levels in an organism. The chapter shows that transgenic mice are a most suitable
      model for studying various aspects of malignant transformation from the molecular
      to the organismal and populational levels.

PMID- 8575894
TI  - Integration of intermediate filaments into cellular organelles.
AB  - The intermediate filaments represent core components of the cytoskeleton and are
      known to interact with several membranous organelles. Classic examples of this
      are the attachment of keratin filaments to the desmosomes and the association of
      the lamin filament meshwork with the inner nuclear membrane. At this point, the
      molecular mechanisms by which the filaments link to membranes are not clearly
      understood. However, since a substantial body of information has been amassed,
      the time is now ripe for comparing notes and formulating working hypotheses. With
      this objective in mind, we review here pioneering studies on this subject,
      together with work that has appeared more recently in the literature.

PMID- 8575895
TI  - Urinary tract infection in women.

PMID- 8575896
TI  - Nocturnal enuresis. A parental nightmare.

PMID- 8575898
TI  - The role of stroke units.

PMID- 8575897
TI  - Erectile dysfunction.

PMID- 8575900
TI  - Ends and means of life: the Supreme Court and withdrawal of nutrition and
      hydration.

PMID- 8575899
TI  - Incontinence in the older woman.

PMID- 8575901
TI  - Childhood immunisation uptake in the Republic of Ireland.

PMID- 8575902
TI  - Medical education, Maastricht and the future.
AB  - Undergraduate medical education is in need of revision: the curriculum is
      overloaded, teaching methods do not equip students for a career of learning, and
      the examination system should be redirected to help students learn more
      effectively rather than act as a barrier to progress. New medical schools such as
      the University of Limburg at Maastricht have pioneered an exciting and innovative
      system of medical education which offer a vision of some of the changes we may
      expect in the future. There is a quiet revolution in medical education which,
      although led by educationalists, is driven by changes in hospital practice and
      economic necessity.

PMID- 8575903
TI  - Facial fractures in Gaelic football and hurling.
AB  - A one year, retrospective, epidemiological study of all facial fractures,
      sustained whilst playing the GAA sports of football and hurling, treated in the
      Cork Regional Hospital was undertaken. The results have been analysed and
      compared to a similar study performed in this unit in 1975. Of 332 patients
      treated for facial fractures, 110 (33%) were injured whilst playing sport and 47%
      of these occurred when playing Gaelic football or hurling (52 injuries in all).
      Eighty per cent of Gaelic football and hurling patients required operative
      treatment. All surgery was performed under general anaesthetic. The numbers of
      hurling fractures have more than halved since 1975-76. This coincides with an
      increase in the numbers hurling, an increase in the use of protective headgear
      and vastly improved coaching. This study demonstrates that improved safety can be
      achieved without diluting sporting enjoyment.

PMID- 8575904
TI  - Notification of meningococcal disease and Haemophilus influenzae meningitis: a
      requirement for public health action.
AB  - ------------------------------------------------------------------------ --------
      --------------------------------------------------------------- -----------------
      ------------------------------------------------------ --------------------------
      meningitis was ascertained for the years 1987-1991. Laboratory record review
      identified positive blood culture and cerebro-spinal fluid isolates for 4 Dublin
      hospitals serving the paediatric population of the Eastern Health Board.
      Infectious disease registers, inspected for evidence of notification, revealed
      than only 44% of culture positive cases had been notified. The notification rate
      for Haemophilus meningitis (33%) was significantly lower than that for
      meningococcal disease (53%). All laboratory identified cases should have been
      notified. Public health assessment is required for each condition as rifampicin
      prophylaxis can prevent secondary cases in close contacts of both diseases.
      Improved notification is essential, not just to comply with the law but more
      importantly, for better management of these diseases.

PMID- 8575906
TI  - Childhood penetrating eye injuries.
AB  - We reviewed 41 children with penetrating eye injuries from birth to 15 years of
      age between August 1982 to May 1990. Male to female ratio was 3.56:1. Thirteen
      (33%) cases resulted in monocular blindness. The distribution of penetrating
      injuries was based on the site of perforation: corneal, corneoscleral and scleral
      groups. The commonest cause of injury was child related from a thrown object
      (42%) and hazardous toys (21%).

PMID- 8575905
TI  - General practitioner views of a new specialist Department of Medicine for the
      Elderly.
AB  - The reactions of General Practitioners (GPs) in an area served by a new
      Department of Medicine for the Elderly (Geriatric Medicine) are described. 89% of
      GPs thought the new service had brought significant benefits to their patients,
      The department operated an over 80 admission policy for acute medical admissions.
      After two years in operation 59% of doctors felt this should be lowered with 4%
      suggesting it should be raised. Rehabilitation and respite admissions were other
      features of the new service that had approval ratings of over 70% by the doctors
      surveyed. It is suggested that a Department of Medicine for the Elderly with a
      policy of rapid assessment and high turnover is appreciated by GPs. While local
      circumstances will often dictate policy it is suggested that an age-related
      admission procedure will minimise difficulty for patient and referring
      practitioner alike.

PMID- 8575907
TI  - Keeping up to date--a challenge for teaching practices.

PMID- 8575908
TI  - Benign neonatal sleep myoclonus.
AB  - Benign neonatal sleep myoclonus is a disorder characterised by abnormal episodic
      jerky movements, which occur exclusively during sleep. When the history is
      suggestive of the diagnosis, and physical examination and basic investigations
      are normal, a confident diagnosis can usually be reached, and other potentially
      more serious neonatal seizure disorders excluded. This allows the doctor to
      reassure the parents as to the prognosis--the condition resolves spontaneously
      within the first year, most often within the first three months, with no
      sequelae. We describe four patients who presented to one unit with this
      condition.

PMID- 8575909
TI  - Routine management of the woman on HRT.

PMID- 8575910
TI  - Supreme Court decision in respect of a ward of court.

PMID- 8575911
TI  - Metastatic bone disease: role of bisphosphonates.

PMID- 8575912
TI  - Secondary prevention in coronary heart disease. Fact: lowering cholesterol saves
      lives.

PMID- 8575913
TI  - Medical options in the treatment of generalised seizures in adults.

PMID- 8575915
TI  - The new anti-epileptic drugs.

PMID- 8575914
TI  - Epilepsy in children.

PMID- 8575916
TI  - Management of hepatitis B.

PMID- 8575917
TI  - Mucocutaneous herpes simplex infections.

PMID- 8575918
TI  - Atopic eczema.

PMID- 8575919
TI  - Childhood immunisation uptake in the Republic of Ireland.

PMID- 8575923
TI  - SOFT Issues in asthma management.
AB  - OBJECTIVES: To ascertain if A/E SHOs checked inhaler technique in asthmatic
      patients and the frequency of patient education. DESIGN: Postal questionnaire
      survey. SUBJECTS A/E SHOs in Northern Ireland and in the Republic of Ireland from
      January-June 1994. RESULTS: 92 questionnaires were analysed from 25 (71%)
      hospitals. 61 (66%) SHOs did not check inhaler technique. The main reason given
      was pressure of work 38 (62%). 32 (33%) and 41 (44%) SHOs had never been shown
      how to use a turbohaler or a spinhaler respectively. 49 (54%) do not advise
      regarding the dangers of passive smoking. 29 (32%) do not inform patients of
      their PEFR. A/E SHOs are often unfamiliar with inhalers and the majority do not
      routinely check inhaler technique in asthmatic patients. Many aspects of
      asthmatic patient education are So Often Forgotten Today in the A/E department.

PMID- 8575921
TI  - Gastrointestinal motility testing--a personal perspective.
AB  - The role of motility tests in the evaluation of some common disorders in which
      motility has been assumed to play a role is reviewed. Three separate areas, non
      cardiac chest pain, constipation and the irritable bowel syndrome are discussed.
      In each area, considerable difficulty in the clinical definition of these
      disorders persists and presents a major obstacle to the evaluation of diagnostic
      tests. With regard to non-cardiac chest pain, it is apparent that gastro
      oesophageal reflux and sensory/perception abnormalities, rather than dysmotility,
      are the predominant factors, and investigations should take account of this.
      While studies of colonic and small intestinal motility have demonstrated various
      abnormal patterns in patients described as suffering from the irritable bowel
      syndrome, the specificity of any of these motor 'abnormalities' remains
      uncertain, and manometry cannot be recommended as a diagnostic tool in this
      context. Considerable advances have been made in our understanding of gut motor
      physiology and in our ability to accurately record motor function in man, the
      basic pathophysiology of many 'functional' gut syndromes remains unclear, and the
      role of dysmotility, in particular, poorly defined.

PMID- 8575925
TI  - Addiction and temporary certification. A proposed change to legislation and it's
      possible implication for clinical practice.
AB  - The Mental Treatment Act (1945) is currently undergoing review to enable Ireland
      to meet it's international obligations. The Green Paper on Mental Health (1992)
      makes a number of suggestions regarding this. One such is the deletion of
      Addiction as sufficient grounds for involuntary admission to a psychiatric
      hospital or unit. This study looked at the possible impact such a proposal might
      have on the doctor's clinical choice in the management of addiction. The
      casenotes and temporary certificates of 191 involuntary admissions to St.
      Brendan's Hospital were examined. 9 cases (4.7%) were admitted for the direct
      effect of addiction, i.e., intoxication or uncomplicated withdrawal. The
      conclusion of this study is that the deletion of the addiction criterion from
      future mental health legislation would, in itself, have little impact on the
      number of committals. This is because the majority of those with evidence of
      Substance Abuse have a concurrent disorder that would be covered by the remaining
      criteria.

PMID- 8575924
TI  - A review of patients on methadone maintenance.
AB  - This study involves a review of 178 patients on a strictly monitored methadone
      maintenance programme. All patients had a minimum of 9 years of intravenous drug
      misuse. 35.7% were HIV positive, 55.7% males and 29% females had previous prison
      sentences. On average patients had undergone 3.26 out-patient and 0.9 in-patient
      detoxification. 46.1% had attempted rehabilitation in the past. Out of 25,470
      urine samples obtained while on the programme, 10.8% were positive for opiates,
      19.2% for benzodiazepines, 32.5% for cannabis, 4.92% for alcohol and 2.27% for
      amphetamines. Long history of misuse, multiple custodial sentences, previous
      unsuccessful rehabilitation and positive HIV status were associated with
      acceptance for maintenance. Frequency of urinalysis, and results triggering dose
      change can effectively reduce illicit drug use.

PMID- 8575920
TI  - Simple closure and follow up H2 receptor antagonists for perforated peptic ulcer-
      immediate survival and symptomatic outcome.
AB  - There is controversy over the optimum treatment of perforated peptic ulcer. Non
      operative management is associated with a high incidence of subsequent operation
      while immediate definitive surgery is associated with a high initial peri
      operative mortality. We have a policy of simple closure and follow up H2-receptor
      antagonists. This study reviews 100 consecutive patients to identify immediate
      survival and subsequent symptomatic results of this surgical policy. The mean age
      was 49 years with 24 patients over 70 years. Sixteen were taking H2-receptor
      antagonists and 20 taking non-steroidal anti-inflammatory drugs on admission.
      Simple closure was performed in 94 and six had definitive surgery as their first
      procedure. The 30 day mortality was 6% (1% for < 70 yrs n = 76, 20% for > 70 yrs
      n = 24). Complete follow up was achieved in 90%, (range 2-80 months). Seventy
      four percent were asymptomatic, 13% intermittently symptomatic and 7% had
      continuous symptoms. Only five patients (6%) required subsequent definitive
      surgery. The policy of simple closure and follow up H2 receptor antagonists for
      perforated peptic ulcer is safe and effective in the long term.

PMID- 8575922
TI  - What do Dublin GPs expect from a psychiatric referral?
AB  - The advent of community psychiatry has tended to blur the interface between
      primary and secondary psychiatric care. We used a postal questionnaire to
      investigate each new referral from general practice to the public outpatient
      clinics of three West Dublin Psychiatric Sectors. 70 referrals, from 35 general
      practitioners, over a four month period in 1991 were analysed, regarding reason
      for referral and prior management in general practice. On average patients had
      seen their GP six times over a period of ten months. Mixed anxiety/depression was
      the most common diagnosis (23%). Medication had been prescribed for 61% of
      patients and 67% had counselling before referral. Common reasons for referral
      were: Access to therapies not available directly to the GP (30%); Failure of
      treatment (20%); To share the burden of chronic care (14%). In only 13% of
      referrals did the GP wish the psychiatrist to take over care. We conclude that
      the GPs surveyed undertake extensive pre-referral management of patients with
      psychological illness. They have well defined expectations of referral and are
      keen to follow up patients themselves. Future plans for community psychiatric
      services should take account of this pattern of care.

PMID- 8575927
TI  - Letter to the Editor

PMID- 8575926
TI  - Rectal examination in hospital patients.
AB  - Rectal examination should be part of the initial examination of the patient
      especially those who are over the age of 50 and/or those with gastro intestinal
      and genito-urinary symptoms. We assessed the rate of rectal examinations carried
      out on acute general medical and surgical admissions over the age of 50 years.

PMID- 8575928
TI  - Current bibliography of the history of science and its cultural influences. 1995.

PMID- 8575929
TI  - A quantitative analysis of modifier mutations which occur in mutation
      accumulation lines in Drosophila melanogaster.
AB  - Seven enzyme activities were measured in Drosophila melanogaster lines in which
      spontaneous mutations had accumulated over about 300 generations under the
      minimum pressure of natural selection. These enzymes included alcohol
      dehydrogenase (ADH), alpha-glycerol-3-phosphate dehydrogenase (alpha GPDH),
      malate dehydrogenase (MDH), isocitrate dehydrogenase (IDH), glucose-6-phosphate
      dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD) and alpha-amylase
      (AMY). A significant genetic variance was observed for some enzyme activities.
      The mutations which alter the enzyme activities are called modifier mutations.
      The magnitudes of the genetic variance in modifier mutations differed greatly
      among enzymes but were often similar between two series of mutation accumulation
      lines (AW and JH). This may therefore indicate that the number of modifiers is
      specific for each enzyme system. The modifier mutation rate is suggested to be
      one of the clues for assessing the maintenance mechanism of protein polymorphism
      in natural populations.

PMID- 8575930
TI  - The genetic basis of murine and human sex determination: a review.
AB  - Determination of mammalian sex depends on the presence or absence of a functional
      testis. Testes are determined by the activity of the testis determining factor
      encoded by the sex determining gene, Y (SRY) located on the Y chromosome.
      Considerable evidence suggests that the SRY gene is the only gene on the Y
      chromosome that is both necessary and sufficient to initiate testis
      determination. Other steps in the mammalian sex determining pathway are unknown,
      although recent advances have shown that mutations in X chromosome and autosomal
      loci are also associated with sex reversal, suggesting the presence of at least
      one other sex determining gene. Duplications of sequences on the short arm of the
      human X chromosome, including the DAX-1 (DSS-AHC critical region on the X
      chromosome, gene 1) gene, are occasionally associated with XY male-to-female sex
      reversal. In addition, mutations in the SRY-related gene SOX9 (SRY-related box)
      are associated with a failure of human testicular determination. Furthermore, the
      occurrence of inherited sex reversed conditions in both mice and men indicate the
      presence of at least one other sex determining gene. Breeding the Y chromosome
      from certain Mus musculus domesticus strains into the laboratory mouse strain
      C57BL/6J results in XY male-to-female sex reversal. This suggests both allelic
      variation of the Sry gene and the presence of autosomal sex determining genes. In
      humans, familial cases of SRY-negative XX males occur. Analysis of the
      transmission of the trait indicates the segregation of an autosomal or X-linked
      recessive mutation. The mutation may be in a gene whose wild-type function is to
      inhibit male sex determination. SRY may trigger male sex determination by
      repressing or functionally antagonizing the product of this gene.

PMID- 8575931
TI  - Naturally-occurring Wolbachia infection in Drosophila simulans that does not
      cause cytoplasmic incompatibility.
AB  - Microbes of the genus Wolbachia are transmitted by their hosts via the maternal
      parent and are responsible for cytoplasmic incompatibility among insect
      populations. This phenomenon can result in Wolbachia spreading through natural
      populations as previously demonstrated in Drosophila simulans. Here we describe
      another Wolbachia infection in D. simulans that does not cause cytoplasmic
      incompatibility. This is a property of the Wolbachia rather than the nuclear
      background. The infection occurs at a low frequency in natural populations from
      eastern Australia. The infection shows perfect maternal transmission in the field
      and does not cause any detectable deleterious effects on its host. These findings
      suggest that the Wolbachia infection behaves like a neutral variant in
      populations. The infection may represent an evolutionary outcome of interactions
      between Wolbachia infections and their hosts.

PMID- 8575932
TI  - Larval foraging behaviour and competition in Drosophila melanogaster.
AB  - Populations of Drosophila melanogaster derived by bidirectional selection for
      high (HA) and low (LA) aggregated oviposition behaviour differ significantly in
      the duration of the larval period and adult size because of differences in the
      developmental profiles for feeding rate over successive phases of larval growth.
      Feeding rates of HA larvae are significantly lower than those of LA larvae during
      the flexible period of growth which precedes attainment of critical mass for
      pupation. Consequently the HA larvae have a slower mean rate of development. In
      the fixed postcritical period of development the feeding rates of HA larvae are
      significantly higher than those of LA larvae. This causes a greater postcritical
      growth increment and larger adult flies. HA and LA larvae respond adaptively by
      changing the expression of components of their foraging behaviour depending on
      whether they are in or out of food. LA larvae exhibit a more flexible pattern of
      response and are also more successful competitors when food resources are
      limiting.

PMID- 8575933
TI  - Equilocality and heterogeneity of constitutive heterochromatin: in situ
      localization of two families of highly repetitive DNA in Dociostaurus genei
      (Orthoptera).
AB  - The chromosome complement of the grasshopper Dociostaurus genei is characterized
      by the presence of constitutive heterochromatin (C-bands) located in the
      centromeric regions of all the chromosomes and in the distal regions of some
      autosomes in the form of supernumerary segments. A sequence analysis was carried
      out to obtain information about the molecular characteristics of both
      heterochromatic regions. Two families of tandemly repetitive DNA (DgT2 and DgA3)
      from D. genei were cloned and characterized. Data obtained from in situ
      hybridization indicate that these families are located solely in the regions of
      constitutive heterochromatin. The DgT2 clone is representative of a family of
      sequences which mainly forms the centromeric C-bands in each chromosome of the
      complement. The DgA3 family is the major component of the distal C-bands
      (supernumerary segments) present in most of the autosomal pairs. These results
      show the existence in D. genei of two different families of repetitive DNA
      restricted to different chromosomal domains. We discuss these results in the
      light of the possible role of chromosomal disposition in the maintenance of the
      differences between heterochromatic DNA from different chromosomal regions and
      the homogenization of DNA sequences from equilocal chromosomal domains.

PMID- 8575934
TI  - Variation in sex-, stage- and tissue-specific expression of the amylase genes in
      Drosophila ananassae.
AB  - Expression of the amylase multigene family of Drosophila ananassae was
      investigated in third-instar larvae and adults. A developmental differentiation
      was found between the Amy1-2 and Amy3-4 gene clusters, the former being
      preferentially expressed in larvae, the latter in adults. During adult life, we
      observed a decrease in Amy1-2 expression in males of certain strans. We have
      raised some arguments for the existence of trans-active regulators, acting as
      repressors of Amy1-2 in adults. The putative repressors might exhibit a
      geographical polymorphism, with a fixed active form in Pacific regions and a
      polymorphic pattern in Africa, thus increasing the diversity observed in adult
      amylase phenotypes. A clear differentiation between the two gene clusters was
      also found in tissue-specific activity along the third-instar larval midgut. In
      the anterior midgut, only Amy1-2 is active, while both gene groups are expressed
      in the posterior midgut, with an additional subzonation within it.

PMID- 8575935
TI  - The histochemistry of NOS.

PMID- 8575936
TI  - Nitric oxide in physiology and pathology.
AB  - Nitric oxide (NO) can exert a multitude of biological actions. NO, formed from L
      arginine by a calcium-dependent enzyme (NO synthase) plays a key physiological
      role in regulating vascular tone and integrity. NO, formed by a constitutive
      neuronal isoform of NO synthase, likewise plays an important neuromodulator role.
      By contrast, high levels of NO can be generated following induction of a calcium
      independent isoform of NO synthase. This excessive production of NO can provoke
      hypotension such as that observed in septic shock, and can exert cytotoxic
      actions leading to tissue injury and inflammation. Selective inhibitors of this
      inducible isoform thus have therapeutic potential in a number of disease states.

PMID- 8575937
TI  - Nitric oxide synthase isozymes antibodies.
AB  - Three isozymes of nitric oxide synthase (NOS) have been identified, cDNAs
      isolated and sequenced, and antibodies produced against each isozyme. Isozyme I
      (found primarily in central and peripheral neuronal cells), II (in cytokine
      induced cells), and III (in endothelial cells) show less than 58% identity in the
      deduced amino acid sequences from humans. Many investigators have produced
      isozyme-specific antibodies and used these antibodies to locate these proteins in
      various cells and tissues. NOS-I is constitutively expressed, and the enzymatic
      activity is regulated by Ca2+ and calmodulin. The anti-NOS-I antibodies have
      allowed investigators to characterize non-adrenergic non-cholinergic neurons as
      nitrergic neurons, revealed NOS-I immunoreactivity in neurons and macula densa
      cells of the kidney and pancreatic islet cells, human skeletal muscle, and to
      demonstrate that various structures within the brain and spinal cord contain NOS
      I. NOS-II is not regulated by Ca2+ and has been implicated in the pathophysiology
      of sepsis and autoimmune diseases. The anti-NOS-II antibodies have localized this
      isoform to infiltrating macrophages in pancreatic islets of diabetic rats,
      infiltrating macrophages and myocytes of a transplant heart model in rats,
      various cell types in bacterially and endotoxin-treated rats, alveolar
      macrophages in areas of inflammation in humans, and vascular smooth muscle cells
      of human atherosclerotic aneurysm. Isoform III is similar to NOS-I in that it is
      constitutively expressed and regulated by Ca2+ and calmodulin. Anti-NOS-III
      antibodies have found that this isoform is relatively specific for endothelial
      cells.

PMID- 8575938
TI  - Studies on the localization and expression of nitric oxide synthase using
      histochemical techniques.
AB  - This review provides an update on the variety of histochemical techniques
      available for the cellular localization and expression of nitric oxide synthase
      in formalin-fixed tissue sections. The techniques of immunohistochemistry and
      NADPH-diaphorase histochemistry are discussed and the suitability of various
      types of probes and reporters which are useful for in situ detection of nitric
      oxide synthase mRNA expression are assessed. Figures are also included which
      illustrate the techniques described and protocols for in situ hybridization and
      NADPH-diaphorase histochemistry.

PMID- 8575940
TI  - Nitric oxide synthase in invertebrates.
AB  - The gas nitric oxide is now recognized as an important signalling molecule that
      is synthesized from L-arginine by the enzyme nitric oxide synthase. This enzyme
      can be localized by different methods, including immunocytochemistry and the
      histochemical reaction for NADPH diaphorase. It has been demonstrated in various
      vertebrate cells and tissues, and recently several studies dealing with the
      production of nitric oxide in invertebrates have been published. Diploblastic
      animals, flatworms and nematodes seem to lack NADPH diaphorase activity but it
      has been found in the rest of the phyla studied. The most frequently reported
      sites for the production of nitric oxide are the central and peripheral nervous
      systems and, in primitive molluscs, the muscle cells. In insects, it has also
      been described in the Malpighian tubules. The roles of nitric oxide in
      invertebrates are closely related to the physiological actions described in
      vertebrates, namely, neurotransmission, defence, and salt and water balance. The
      recent cloning of the first nitric oxide synthase from an invertebrate source
      could open interesting avenues for further studies.

PMID- 8575939
TI  - Histochemical methods for detecting nitric oxide synthase.
AB  - The three isoforms of nitric oxide synthase (NOS), neuronal (nNOS), endothelial
      (eNOS), and inducible (iNOS), can be visualized in cells and tissues by NADPH
      diaphorase (NADPH-d) histochemistry, immunocytochemistry and in situ
      hybridization. Histochemical demonstration of NADPH-d shows the formazan final
      reaction product as a solid blue deposit. The ultrastructural localization of
      NADPH-d in the rat hippocampus showed an electron-dense deposit on membranes
      predominantly of the endoplasmic reticulum. The immunohistochemical demonstration
      of nNOS, using the nickel enhancement technique, shows positive reaction product
      over the dendrites and the soma of the nerve cell in the rat brain.
      Ultrastructural localization of nNOS in whole mount preparations of myenteric
      plexus and circular smooth muscle from guinea-pig ileum shows that NOS
      immunoreactivity was patchily distributed in myenteric neurones and was not
      specifically associated with any intracellular organelles or with plasma
      membranes. In situ hybridization, using radio-labelled probes, was used to study
      nNOS mRNA in lumbar dorsal root ganglia after peripheral transection of the
      sciatic nerve in rats. Labelling of the NOS mRNA-positive neurones is observed as
      a series of dense granules over the entire cell. NADPH-d histochemistry,
      immunocytochemistry and in situ hybridization each have a significant role to
      play in the localization of NOS. NADPH-d detects an enzyme associated with the
      NOS molecule, immunocytochemistry detects the NOS molecule, and in situ
      hybridization detects mRNA for NOS. Therefore, if each of these techniques is
      applied in carefully controlled experiments, consideration of the accumulated
      data should be valuable in revealing insights into the biology of NOS.

PMID- 8575941
TI  - Inducible nitric oxide synthase in inflammation.
AB  - Inflammation, the reaction of vascularized tissue to local injury, not only
      limits the effects of injury; it may also be the underlying pathological process
      which initiates or sustains disease. In this paper, the evidence is reviewed for
      a role for nitric oxide (NO) as a chemical indicator of inflammation and
      inflammatory diseases.

PMID- 8575943
TI  - Neuronal nitric oxide synthase immunoreactivity in the respiratory tract of the
      frog, Rana temporaria.
AB  - Physiological and histochemical studies have recently supported the notion that
      nitric oxide (NO) is the transduction signal responsible for the non-adrenergic,
      non-cholinergic relaxation of the vasculature as well as the airways of the
      mammalian lung. We report the presence of immunoreactivity to NO synthase (NOS)
      in nerve cell bodies and nerve fibres in the neural plexus of the buccal cavity
      and lungs of the frog, Rana temporaria, using the indirect immunocytochemical
      technique of avidin-biotin and the NADPH-diaphorase technique. The neural ganglia
      located next to the muscle layer and within the connective tissue of the buccal
      cavity were partially immunoreactive for NOS. In the lungs, NOS immunoreactivity
      occurred in nerve cell bodies, as well as in both myelinated and unmyelinated
      nerve fibres. Fine nerve fibres immunoreactive to NOS were observed within the
      muscle fibre bundles and next to the respiratory epithelium. Both the presence of
      NOS immunoreactivity and the positive histochemical reaction for NADPH-diaphorase
      in the neural plexus of amphibian respiratory tract suggests a broad evolutionary
      role for NO as a peripheral neurotransmitter.

PMID- 8575945
TI  - Cigarette smoking still smolders after all these years.

PMID- 8575944
TI  - Nitric oxide synthase-containing neurons in rat parasympathetic, sympathetic and
      sensory ganglia: a comparative study.
AB  - In rats, the distribution of nerve structures staining for NADPH-diaphorase, and
      showing immunoreactivities for nitric oxide synthase (NOS), tyrosine hydroxylase
      and various neuropeptides was studied in sensory ganglia (dorsal root, nodose and
      trigeminal ganglia), in sympathetic ganglia (superior cervical, stellate, coeliac
      superior and inferior mesenteric ganglia), parasympathetic ganglia
      (sphenopalatine, submandibular, sublingual and otic ganglia), and in the mixed
      parasympathetic/sympathetic ganglia (major pelvic ganglia). The coincidence of
      neuronal cell bodies with strong NOS-immunoreactivity and strong NADPH diaphorase
      reactivity was almost total. The relative proportions of NOS-immunoreactive nerve
      cell bodies were largest in parasympathetic ganglia and major pelvic ganglia
      followed by sensory ganglia. In sympathetic ganglia no NOS-immunoreactive
      neuronal cell bodies could be detected. In parasympathetic and major pelvic
      ganglia, there was a very significant neuronal co-localization of
      immunoreactivities for NOS and vasoactive intestinal polypeptide (VIP). This was
      almost total in major pelvic ganglia, in which NOS-/VIP-immunoreactive nerve cell
      bodies were separate from sympathetic (tyrosine hydroxylase-/neuropeptide Y
      immunoreactive), suggesting that NOS-/VIP-immuno-reactive neurons might also be
      parasympathetic.

PMID- 8575946
TI  - Checklist enables rapid screening for major psychiatric disorders.

PMID- 8575942
TI  - Histochemistry of nitric oxide synthase in the nervous system.
AB  - Nitric oxide synthase, which generates the physiological messenger molecule
      nitric oxide, and its associated NADPH diaphorase (NADPHd) activity are
      distributed throughout selective neuronal populations of the central and
      peripheral nervous system. Considerable evidence has been accumulated to indicate
      that NADPHd activity labels cells lacking neuronal nitric oxide synthase, i.e.,
      the specificity of the reaction has to be considered for the reliable detection
      of the enzyme in neuronal but also non-neuronal tissue. In the present review,
      critical aspects of nitric oxide synthase visualization in neurones, using its
      NADPHd activity, are discussed. Furthermore, the organization of the central and
      peripheral nitric oxide synthase-containing neuronal systems is described. Nitric
      oxide synthase is present in local cortical and striatal neurones, hypothalamic
      magnocellular neurones, mesopontine cholinergic neurones, cerebellar
      interneurones, preganglionic sympathetic and parasympathetic neurones, neurones
      in parasympathetic autonomic and enteric ganglia and primary viscero-afferent
      neurones. Finally, injury-related alterations in nitric oxide synthase activity
      are briefly outlined. In this respect, the histochemistry of nitric oxide
      synthase may represent a valuable marker for neurochemical, if not structural,
      alterations observed in neural diseases, regeneration and transplantation.

PMID- 8575947
TI  - A mnemonic approach to the evaluation of chest x-ray films.

PMID- 8575949
TI  - Cigarette availability to minors.
AB  - Each year, more than 1 million children and adolescents begin smoking, and an
      average of 24% of high school students report smoking, despite existing laws that
      prohibit the sale of tobacco to minors. In this study, the authors observed an 11
      year-old boy attempt to purchase cigarettes at 57 retail establishments in
      western Pennsylvania to determine if the existing laws do, indeed, limit
      children's access to buy cigarettes. This study took place between August 15,
      1993, and October 2, 1993. The establishments included convenience stores, gas
      stations, liquor distributors, and restaurants. One of the researchers entered
      each establishment to look for the posting of the state law prohibiting the sale
      of cigarettes to minors after their underage subject had requested cigarettes
      from the salesclerks. The researcher also inquired of the salesclerks if they
      were aware of the state law. In 30 of the 57 attempts (53%), the 11-year-old
      student would have been able to purchase cigarettes. Of these attempts, 53% would
      have sold them on his first request, while 47% would have sold them to him if he
      indicated that the cigarettes were for his dad. Only 3 of the 57 establishments
      (5.2%) posted the law, and 54 of the 57 clerks (95%) were aware of the cigarette
      law.

PMID- 8575948
TI  - Smoking cessation: a clinical study of the transdermal nicotine patch.
AB  - Although cigarette smoking is a declining trend in the United States, the amount
      of cigarettes consumed by the American public is the same today as in 1964. The
      role of cigarette smoking in many disease processes is publicly well known, and
      smoking cessation has been proved to reduce risk for some diseases, but the
      various methods of cessation are often met with a high rate of treatment failure
      or relapse. In this study, the short-term efficacy of nicotine-replacement
      therapy by way of the transdermal patch system was evaluated in 110 patients in a
      family practice setting. Patches were tapered from 21 mg of nicotine to 14 mg to
      7 mg, each for 30 days. Subjects wore one patch for every 24 hours and were
      instructed not to smoke. Telephone follow-up was used at 2 to 3 weeks to check
      smoking status and inquire for side effects, and further follow-up of those who
      had completed the 3-month program was initiated 6 months after the program began.
      Nineteen patients never filled the prescription, and six were lost to follow-up.
      Of the 85 who finished the program, 35% were still not smoking at 6 months after
      the study began. The other 65% had relapsed. Side effects were mild and were
      mainly related to skin irritation at the patch site and abnormal dreams.
      Combinations of this cessation method with physician counseling and other
      behavioral methods should improve the success rate of this encouraging treatment.

PMID- 8575951
TI  - Impact of antitrust laws on physician networking and rural communities.
AB  - After reviewing the history of antitrust legislation and established zones of
      safety for providers and the application of antitrust laws to the healthcare
      industry in two earlier installments, the authors explore the consequences of the
      vigorous application of antitrust laws to physician networking, with an emphasis
      on rural communities. They review common exemptions to antitrust laws that
      maintain the uneven distribution of power in the evolving healthcare market.
      Acknowledging the tenuous ground that providers hold in the struggle for control
      of the healthcare industry, the authors argue for greater consideration of the
      unique circumstances and barriers that tend to prohibit the formation of strong,
      physician-sponsored, integrated healthcare networks. The authors have tested the
      climate for relief from the antitrust enforcement agencies in Washington, DC, and
      have found no easing of antitrust legislation forthcoming. However, following the
      resolution of several antitrust cases in recent months, barriers to physician-led
      organizations appear to be lessening. The authors close with a review of several
      strategies to minimize the risk of antitrust challenges.

PMID- 8575950
TI  - Osteopathic postdoctoral training institution: the osteopathic 'road map' to
      graduate medical education viability.

PMID- 8575952
TI  - Twenty-year experience with the Mentor bladder pacemaker.
AB  - Twenty years after placement of a Mentor bladder pacemaker, a 38-year-old woman
      with spina bifida cystica still has controlled detrusor contraction and complete
      bladder emptying. The varied treatment modalities for this difficult group of
      patients has included electronic bladder stimulation. Although no longer commonly
      used, electronic bladder stimulation has shown long-term efficiency in this
      patient.

PMID- 8575953
TI  - Food safety requires vision and vigilance. Emerging disease in young turkeys
      causes heavy mortality.

PMID- 8575954
TI  - AAEP acupuncture lecture gets point across.

PMID- 8575955
TI  - Comments on loop colostomy in horses.

PMID- 8575956
TI  - Knowledge of fish anatomy important.

PMID- 8575958
TI  - System for reporting adverse reactions.

PMID- 8575957
TI  - Questions about pathogen reduction.

PMID- 8575959
TI  - We need a less expensive way to produce effective veterinarians.

PMID- 8575960
TI  - What is your diagnosis? Suspected caudal esophageal mass in a dog.

PMID- 8575961
TI  - ECG of the month.

PMID- 8575963
TI  - Developing direction for your practice.
AB  - As the leader in your practice, you can help shape the direction of your
      business. Analyze your situation and decide where change is needed. The first
      step is to develop a clear vision that can create excitement in yourself and your
      employees. A staff meeting is a good forum for sharing your vision. The second
      step is to develop a mission statement so that you and your clients, employees,
      suppliers, and community know where you are headed. The third step is to adopt a
      business strategy (or combination of business strategies) that you are
      comfortable with. The final step is to define specific goals that allow you to
      adapt to changes in your professional environment. To quote the great
      philosopher, the Cheshire cat from Alice in Wonderland, "if you don't know where
      you are going, any road will take you there."

PMID- 8575962
TI  - Laryngeal obstruction secondary to brodifacoum toxicosis in a dog.

PMID- 8575965
TI  - The United States Pharmacopeia Veterinary Practitioners' Reporting Program.

PMID- 8575964
TI  - Due process and the rights of a veterinarian in an administrative hearing.

PMID- 8575966
TI  - Evaluation of a hypertonic sodium chloride/dextran solution for treatment of
      traumatic shock in dogs.
AB  - OBJECTIVE: To compare the efficacy of 7% NaCl solution (hypertonic saline) in 6%
      dextran 70 solution (HSD) with that of lactated Ringer's solution (LRS) for
      treatment of dogs in traumatic shock. DESIGN: Prospective, randomized, clinical
      study. ANIMALS: 16 traumatized adult dogs with clinical signs of shock.
      PROCEDURE: Physical, hemodynamic, blood gas, and clinical chemistry measurements
      were performed prior to treatment. Initial treatment consisted of HSD (n = 8) or
      LRS (n = 8) administered as a bolus (5 ml/kg of body weight, IV) over a 3-minute
      period, followed by administration of additional LRS and other treatments to
      restore hemodynamic and physical criteria to within reference limits.
      Measurements were repeated for 3 hours after initial treatment. The volumes of
      LRS and HSD administered were recorded hourly. Degree of injury was scored by
      using a trauma severity index. RESULTS: Dogs responded similarly to the
      treatments, and all but 3 dogs survived to be discharged. The amount of fluid
      administered to dogs in the HSD group over the final 2 hours of the study was
      significantly less than that administered to the dogs in the LRS group. Serum
      sodium concentration and osmolality of the dogs in the HSD group were not
      significantly greater than those values in the LRS group. Bradyarrhythmias were
      observed in 2 dogs in the HSD group. CLINICAL IMPLICATIONS: Hypertonic sodium
      chloride/dextran solution is safe and effective for resuscitating dogs in
      traumatic shock. Seven percent NaCl in 6% dextran 70 may reduce the need for
      isotonic fluids in the hours after initial resuscitation.

PMID- 8575967
TI  - Use of orally administered succimer (meso-2,3-dimercaptosuccinic acid) for
      treatment of lead poisoning in dogs.
AB  - OBJECTIVE: To determine whether succimer (meso-2,3-dimercaptosuccinic acid) would
      be effective in reducing blood lead concentration in dogs with naturally acquired
      lead poisoning and whether treated dogs would develop clinically important
      adverse effects. DESIGN: Prospective case series. ANIMALS: 13 dogs with moderate
      to-high blood lead concentrations (39 to 120 micrograms/dl) and clinical signs of
      lead poisoning. PROCEDURE: Dogs were treated with succimer (10 mg/kg of body
      weight, PO, q 8 h) for 10 days. Blood and urine samples were analyzed for lead
      concentration before, during, and after treatment with succimer. RESULTS: Mean
      blood lead concentrations on days 0, 3, 7, and 20 were 70.6, 32.7, 16.8, and 27.6
      micrograms/dl, respectively. Mean blood lead concentrations decreased 53.6, 76.2,
      and 60.9% from pretreatment value on days 3, 7, and 20, respectively. Mean urine
      lead concentrations on days 0, 3, 7, and 20 were 70.0, 485.4, 254.3, and 28.3
      micrograms/dl, respectively. CLINICAL IMPLICATIONS: In dogs with naturally
      acquired lead poisoning, succimer administered orally for 10 days effectively
      reduced blood lead concentrations and eliminated clinical signs of lead
      poisoning.

PMID- 8575968
TI  - Effect of dietary protein content on behavior in dogs.
AB  - OBJECTIVE: To determine the effect that feeding diets containing a low (17%),
      medium (25%), or high (32%) protein content would have on behavior in dogs.
      DESIGN: Prospective, controlled study. ANIMALS: 12 dogs with dominance
      aggression, 12 dogs with hyperactivity, 12 dogs with territorial aggression, and
      14 control dogs without behavioral problems. PROCEDURE: Dogs were fed each of the
      diets for a 2-week period, and owners were instructed to score their dogs'
      behavior on a daily basis. RESULTS: Behavior of the dogs with dominance
      aggression, dogs with hyperactivity, and control dogs was unchanged by the
      dietary manipulations. Territorial aggression was significantly reduced when dogs
      were fed the low- or medium-protein diet, compared with territorial aggression
      when fed the high-protein diet. Post hoc analysis indicated that this effect was
      attributable to a marked reduction in aggression in a subset of the group (n = 7)
      in which territorial aggression was a result of fear. CLINICAL IMPLICATIONS:
      Results of this study suggest that a reduction in dietary protein content is not
      generally useful in the treatment of behavior problems in dogs, but may be
      appropriate in dogs with territorial aggression that is a result of fear.

PMID- 8575969
TI  - Surgical treatment of tracheal collapse in dogs: 90 cases (1983-1993).
AB  - OBJECTIVE: To determine factors associated with long-term outcome in dogs with
      tracheal collapse treated with extraluminal polypropylene C-shaped stents.
      DESIGN: Retrospective case series. ANIMALS: 90 dogs. PROCEDURE: Medical records
      of dogs with surgically treated tracheal collapse were reviewed. Follow-up was
      obtained either by recheck at the veterinary teaching hospital only (n = 10) or
      by telephone interviews with referring veterinarians and owners (n = 35),
      referring veterinarians alone (n = 23), or owners alone (n = 16). The chi 2 test
      was used to determine which factors were associated with long-term outcome.
      RESULTS: 11 breeds were represented. Yorkshire Terriers, Poodles, and Pomeranians
      were most common. Median age at the time of surgery was 6.8 years. Median weight
      was 2.9 kg. Severity of collapse ranged from grade II to grade IV. Dogs < 6 years
      old had more severe collapse than did dogs > or = 6 years old. Dogs > or = years
      old had more postoperative complications and a poorer longterm outcome than did
      dogs < 6 years old. 17 dogs required permanent tracheostomy, 10 within 24 hours
      after surgery. CLINICAL IMPLICATIONS: Surgical placement of extraluminal
      polypropylene C-shaped stents was an effective method of attenuating clinical
      signs of tracheal collapse. Dogs < 6 years old had more severe tracheal collapse
      but did better after surgery than did dogs > or = 6 years old.

PMID- 8575970
TI  - Radiographic findings in cats with intranasal neoplasia or chronic rhinitis: 29
      cases (1982-1988).
AB  - OBJECTIVE: To compare radiographic findings and determine useful criteria to
      differentiate between intranasal neoplasia and chronic rhinitis in cats. DESIGN:
      Retrospective study. ANIMALS: Cats with chronic nasal disease caused by neoplasia
      (n = 18) or by chronic rhinitis (n = 11). PROCEDURE: Radiographs were reviewed by
      3 radiologists, followed by group review. Diagnosis was determined by intranasal
      biopsy or necropsy, and specimens were reviewed by a pathologist to confirm cause
      and histologic diagnosis. RESULTS: Lymphosarcoma was the most common (n = 5) of
      the 6 histopathologic types in the neoplasia group. Cats in the neoplasia and
      chronic rhinitis groups had a high prevalence of aggressive radiographic lesions.
      Prevalence of a facial mass in cats with neoplasia (8/18) versus in those with
      chronic rhinitis (4/11) and of deviation (9/18 vs 6/11, respectively) or lysis
      (12/18 vs 7/11) of the nasal septum was similar. However, significantly (P =
      0.02) more cats with neoplasia than with chronic rhinitis (13/16 vs 3/7,
      respectively) had unilateral turbinate destruction/lysis. Additionally,
      unilateral lateral bone erosion and loss of teeth associated with adjacent
      intranasal disease were more prevalent in cats with neoplasia (7/8 and 5/18,
      respectively) than in cats with chronic rhinitis (1/3 and 0/11, respectively).
      CLINICAL IMPLICATIONS: Features that may assist in radiographic diagnosis of
      neoplasia include the appearance of unilateral aggressive lesions, such as lysis
      of lateral bones, nasal turbinate destruction, and loss of teeth. Bilaterally
      symmetric lesions are more suggestive of chronic rhinitis than of neoplasia.

PMID- 8575971
TI  - Stability of porcine reproductive and respiratory syndrome virus in the presence
      of fomites commonly found on farms.
AB  - OBJECTIVE: To determine the survival of porcine reproductive and respiratory
      syndrome virus (PRRSV) on nonliving substances (fomites) at 25 to 27 C. DESIGN:
      Prospective controlled study. SAMPLE POPULATION: 3 solid, 6 porous, and 7 liquid
      fomites. PROCEDURE: The fomites were contaminated with known concentrations of
      PRRSV. Samples for virus isolation were obtained on day 0 through day 11, assayed
      in cell cultures, and stained with fluorescent antibody conjugate. RESULTS: The
      virus was recovered only on day-0 samples of alfalfa, wood shavings, straw,
      plastic, boot rubber, and stainless steel. Virus was isolated from city water
      through day 11, from well water through day 9, and from 2 buffer solutions for 4
      and 6 days. The virus was isolated only on day 0 from swine saliva, urine, and
      fecal slurry. CLINICAL IMPLICATIONS: Results indicated that PRRSV is a fairly
      labile virus, but because of its duration of viability in water, contamination of
      drinking water and lagoons by PRRSV-shedding swine would serve as sources of
      virus to infect susceptible swine.

PMID- 8575972
TI  - Effects of perinatal vaccination on humoral and cellular immune responses in cows
      and young calves.
AB  - OBJECTIVE: To examine the effects of perinatal vaccination on cellular and
      humoral responses in cows and on passive transfer of antibodies and cells to
      calves, and to assess the role of maternal antibodies in vaccination responses of
      neonatal calves. DESIGN: Prospective randomized control trial. ANIMALS: 52 beef
      cows and their calves. PROCEDURES: Assigned cows were vaccinated twice during the
      last month of gestation. Assigned calves were vaccinated at day 10 after birth.
      Antibody concentrations and cellular responses to bovine respiratory syncytial
      virus (BRSV) and bovine herpesvirus type 1 (BHV-1) were measured in blood and
      colostrum of cows and in blood of calves. Calves were assessed for passive
      transfer of lymphocytes. RESULTS: At parturition, serum antibody concentrations
      to BRSV as well as BHV-1- and BRSV-specific blastogenic responses were
      significantly higher in vaccinated cows. After birth, calves from vaccinated cows
      had significantly higher concentrations of BRSV-specific serum antibodies, but
      not BHV-1 specific antibodies. Calves did not develop delayed-type
      hypersensitivity responses to BRSV. At weaning, lymphocytes from neonatally
      vaccinated calves had significantly higher values for virus-specific
      proliferation than did lymphocytes from unvaccinated calves; however, significant
      differences were not detected between groups after vaccination at weaning.
      CLINICAL IMPLICATIONS: Administration of modified-live viral vaccines can boost
      systemic humoral and cellular responses to BRSV and BHV-1 in cows. Neonatal
      calves can be immunologically primed by vaccination with modified-live virus
      vaccines. Virus-specific memory cells persist in most calves until weaning.

PMID- 8575973
TI  - Evaluation of an agar gel immunodiffusion test kit for detection of antibodies to
      Mycobacterium paratuberculosis in sheep.
AB  - OBJECTIVE: To determine whether a commercially available agar gel immunodiffusion
      test approved for detecting antibodies to Mycobacterium paratuberculosis in
      cattle could be used for sheep. DESIGN: Experimental trial. SAMPLE POPULATION:
      Serum samples from 27 sheep confirmed to have paratuberculosis by means of acid
      fast staining of smears of ileal mucosa, histologic examination of tissues, or
      bacteriologic culture; 7 sheep with clinical signs of paratuberculosis; and 55
      sheep from 5 uninfected flocks. PROCEDURE: Serum samples were tested concurrently
      with the commercially available test and with a previously validated agar gel
      immunodiffusion test. Multiple samples collected from 13 infected sheep over a
      period of 6 years were also tested so that each test's ability to detect onset of
      seropositivity could be compared. RESULTS: For both tests, results for samples
      from all 55 uninfected sheep were negative, results for samples from 32 of the 34
      sheep with paratuberculosis were positive, and results for the remaining 2 sheep
      with paratuberculosis were negative. Results of both tests were in agreement for
      50 of 54 samples obtained from 13 infected sheep over time. The 4 samples for
      which results of the 2 tests disagreed were the fourth, eighth, and ninth of 10
      samples from 1 sheep and the first of 6 samples from a second sheep. For all 4
      samples, the commercially available assay yielded a weak-positive result, but the
      previously described test yielded a negative result. CLINICAL IMPLICATIONS: The
      commercially available agar gel immunodiffusion test approved for use in cattle
      may be useful in the differential diagnosis of paratuberculosis in sheep.

PMID- 8575974
TI  - Use of antimicrobial-impregnated polymethyl methacrylate beads for treatment of
      chronic, refractory septic arthritis and osteomyelitis of the digit in a bull.
AB  - A 6-year-old 895-kg Angus bull was evaluated for a 6-month history of left hind
      limb lameness that was refractory to antimicrobial treatment. On physical
      examination, there was soft-tissue swelling associated with the lateral digit.
      Radiography revealed septic arthritis of the distal interphalangeal joint and
      osteomyelitis of the distal and middle phalanges. Treatment included debridement
      and lavage. Bacteriologic culture of debrided tissues yielded aerobic and
      anaerobic organisms. Antimicrobials were administered parenterally and locally in
      the form of antimicrobial-impregnated polymethyl methacrylate beads. The limb
      also was placed in a cast to promote ankylosis. The bull recovered, and the digit
      was salvaged.

PMID- 8575975
TI  - Immobilization of guanacos by use of tiletamine/zolazepam.
AB  - Adult male guanacos were immobilized by use of tiletamine/zolazepam. The
      effective dosage (mean +/- SD) was 5.0 +/- 1.1 mg/kg of body weight. Mean time
      from injection to immobilization was 7.3 minutes. Usually, immobilization was of
      sufficient duration (mean, 61 minutes) to allow guanacos to be weighed, measured,
      and to have ear tags inserted and blood samples collected. Adverse effects
      included twitching and rigidity of muscles, salivation, chewing movements,
      retching, vocalization, and stumbling during the recovery phase. All guanacos
      recovered without apparent complications.

PMID- 8575976
TI  - Specialized gene expression in the epididymis.

PMID- 8575977
TI  - Enhancement of sperm function for treatment of male infertility.

PMID- 8575978
TI  - NCAM mediates adhesion between gonocytes and Sertoli cells in cocultures from
      testes of neonatal rats.
AB  - During neonatal development of the rat testis, gonocytes resume mitosis and
      display renewed motility to migrate toward the basal lamina, two events that
      occur in vitro when these cells are cocultured with Sertoli cells. However,
      although substantial evidence suggests that development of gonocytes depends on
      Sertoli cells, little is known of how these cell types interact beyond our
      previous observations that they communicate via gap junctions and adhere avidly
      to each other. In the present study, we utilized several approaches to examine
      the mechanism by which gonocytes adhere to Sertoli cells in vitro. First, we
      characterized this attachment in general by (1) determining its susceptibility to
      brief trypsinization in decreasing concentrations of Ca2+, (2) assessing the
      ability of gonocytes to adhere to Sertoli cells at reduced temperature, and (3)
      examining the effect of phospholipase C treatment on the number of gonocytes
      attached to a Sertoli cell monolayer. Because the findings suggested that a non
      cadherin mechanism is involved, we used immunofluorescence to identify the
      presence of neural cell adhesion molecule (NCAM) at virtually all gonocyte
      Sertoli cell (and Sertoli cell-Sertoli cell) boundaries and found that incubation
      of cocultures in the continuous presence of NCAM antibodies caused release of
      essentially all gonocytes (but not Sertoli cells) from the monolayer. We also
      found, in (3) above, that gonocyte-Sertoli cell adhesion was very susceptible to
      phospholipase C in cocultures isolated from newborns and maintained in vitro for
      2 hours or 1 day but not in cultures maintained for 3 days. Moreover, cells
      isolated from pups 5 days old were as resistant to enzyme treatment at 2 hours
      postplating as were cultures from newborns after 3 days in vitro. Thus, the way
      in which gonocytes adhere to Sertoli cells appears to change during the immediate
      postnatal period, as reflected by the observed change in phopholipase
      sensitivity, perhaps indicating production of a phospholipase C-resistant NCAM
      isoform by several days after birth. These data constitute new information on the
      way in which postnatal gonocytes adhere to Sertoli cells and provide a basis for
      future work in our ongoing exploration of germ cell development in the neonatal
      rat testis.

PMID- 8575979
TI  - The distribution of connexin 43 is associated with the germ cell differentiation
      and with the modulation of the Sertoli cell junctional barrier in continual
      (guinea pig) and seasonal breeders' (mink) testes.
AB  - To test whether the gap junction protein connexin 43 (Cx43) is associated with
      germ cell differentiation and with the Sertoli cell junctional blood barrier, we
      recorded the temporal changes in its distribution before birth, through the
      neonatal period, puberty, and adulthood in guinea pig, and throughout the annual
      seasonal reproductive cycle in the mink. We used the immunoperoxidase labeling
      technique on Bouin's perfused-fixed testes and with site-specific polyclonal
      affinity-purified antibodies against Cx43. Cx43 was localized between Leydig
      cells in fetal guinea pig testis. In this species, after birth, the appearance of
      Cx43 concurred with the onset of spermatogenesis. In the seminiferous epithelium,
      the distribution of Cx43 coincided with the gap junctions of the Sertoli cell
      junctional blood barrier. In guinea pig and mink, the distribution of the protein
      in the tubules changed in accordance with the germ cell differentiation in a
      stage-dependent manner and with the modulation, i.e., the assembly and
      disassembly of the junctional barrier accompanying the translocation of
      spermatocytes into the lumenal compartment. In the mink, the reaction product
      persisted during testicular regression but showed a similar distribution from one
      tubule to the next. In this paper, we documented the existence of a temporal
      correlation between the appearance of the gap junction protein Cx43 and both the
      germ cell differentiation and the modulation in the junctional barrier between
      Sertoli cells. The paper also discusses the possibility that cell-to-cell
      communications, generally attributed to gap junctions, may help changes in the
      barrier to take place in coordination with spermatogenesis.

PMID- 8575980
TI  - Deformation of the rat Sertoli cell by oral administration of carbendazim (methyl
      2-benzimidazole carbamate).
AB  - Carbendazim (methyl 2-benzimidazole carbamate; MBC) has been reported to disrupt
      the microtubules of Sertoli cells in the rat, suggesting that the cells exposed
      to carbendazim would fail to maintain their shape due to the loss of their
      cytoskeleton. The present study was performed to determine whether exposure to
      carbendazim induced Sertoli cell deformation. For this purpose, changes in the
      shape and position of Sertoli cell nuclei, that appear to be associated with
      changes in the shape of the cells themselves, were observed in stage VI-VII
      seminiferous tubules of rat testis at 3 hours following treatment. Light
      microscopy and computer-aided three-dimensional reconstruction were also
      performed to survey the outline of the body. In the controls, parallel-positioned
      nuclei (nuclei with their longer axis parallel to the basement membrane),
      perpendicular-positioned nuclei (nuclei with their longer axis perpendicular to
      the basement membrane), and round-shaped nuclei (nuclei showing a round or
      regular triangular profile) accounted for approximately 52%, 35%, and 13% of the
      total, respectively. In Sertoli cells showing carbendazim-induced sloughing of
      germ cells, however, parallel-positioned nuclei accounted for 21% and the round
      shaped nuclei for 51% of the total. Approximately 69% of perpendicular-positioned
      nuclei were located in the basal part of the cells in the controls, compared with
      95% in tubules showing carbendazim-induced sloughing. These changes in individual
      parameters were significantly different (alpha < 0.05). Light microscopy and
      computer-aided reconstruction indicated that the body region of Sertoli cells in
      the control testis was columnar in shape, whereas that of Sertoli cells that
      showed sloughing was conical. These findings suggest that Sertoli cell cytoplasm,
      following carbendazim-induced sloughing, moves toward the base of the cellular
      axis.

PMID- 8575981
TI  - Testicular capillary permeability: the movement of luteinizing hormone from the
      vascular to the interstitial compartment.
AB  - It has previously been shown in several species that pulses of luteinizing
      hormone (LH) in peripheral serum are followed within 10-20 minutes by pulses of
      testosterone. Whether or not LH pulses directly stimulate Leydig cells to produce
      the testosterone pulses would depend on the vascular permeability of LH within
      that physiologically relevant time. In the present experiments, the capillary
      permeability of the testicular microvasculature was characterized in adult rats,
      and the relative permeability to LH was determined. Adult male rats were prepared
      for in vivo micropuncture and testes were infused with 3H-water, 14C-urea, 14C
      polyethylene glycol (PEG), and 3H-dextran directly into the testicular surface
      artery. Testicular interstitial fluid (TIF) and testicular venous plasma were
      collected at 5 minutes, 10 minutes, and 15 minutes after initiation of isotope
      infusion. Data were recorded as isotope concentration in TIF as a proportion of
      the isotope concentration in testicular venous plasma collected at the same time
      period. 3H-water movement into the TIF from blood was rapid reaching 50% of serum
      values within 15 minutes. 14C-PEG and 3H-dextran were largely excluded from the
      TIF, typically not exceeding 5-10% of serum concentrations. In subsequent
      experiments, 125I-LH was infused using the same protocol. 125I-LH concentrations
      in TIF were 3.6 +/- 2.0% of plasma concentrations 10 minutes after initiation of
      infusion. Preceding the 125I-LH infusion experiments with 5-day hypophysectomy or
      with LH pulses delivered either 10 minutes or 4 hours prior to the initiation of
      infusion did not alter the capillary permeability of 125I-LH. These data
      demonstrate the restricted availability of LH to the TIF. This implies that
      Leydig cells are not exposed to LH pulses through the TIF and raises the question
      whether LH pulses directly stimulate testosterone pulses.

PMID- 8575982
TI  - Low levels of nitric oxide promote human sperm capacitation in vitro.
AB  - The influence of nitric oxide on human sperm hyperactivation and capacitation, as
      well as its mechanism of action and its possible origin from spermatozoa were
      studied. Percoll-washed spermatozoa from healthy volunteers were incubated in
      Ham's F-10 medium supplemented or not with the nitric oxide-releasing agents,
      diethylamine-NONOate or spermine-NONOate, in combination or not with superoxide
      dismutase or catalase (scavengers for the superoxide anion and for hydrogen
      peroxide, respectively), or with sodium nitrate, sodium nitrite, or preincubated
      NONOates. Sperm hyperactivation, capacitation, and nitric oxide synthase activity
      were determined. High concentrations (0.3 to 1 mM) of NONOates reduced sperm
      motility. However, a lower concentration (0.1 mM) of the two NONOates had no
      effect on the percentage of sperm motility or of hyperactivation but resulted in
      a significant increase in sperm capacitation (24% +/- 4%) when compared to that
      of control spermatozoa (Ham's F-10 alone, 12% +/- 2%). Nitric oxide released by
      the NONOates appeared responsible for this effect because sodium nitrate or
      nitrite or preincubated NONOates (to exhaust the formation of nitric oxide) had
      no influence on sperm capacitation. Catalase, but not superoxide dismutase,
      abolished the capacitating action of the NONOates. No nitric oxide synthase
      activity was detected in spermatozoa, whether they were in their basal state or
      already capacitated. Furthermore, the nitric oxide synthetase inhibitor L-NG
      nitroarginine methyl ester did not block sperm capacitation induced by fetal cord
      serum ultrafiltrate. It is therefore concluded that, although spermatozoa do not
      possess detectable nitric oxide synthase activity, low levels of nitric oxide
      induce human sperm capacitation, and this action likely involves hydrogen
      peroxide.

PMID- 8575983
TI  - Sperm immobilizing activity of a synthetic bioactive peptide 20-44 of 37-kDa
      cationic antimicrobial protein (CAP37) of human neutrophils.
AB  - We have previously reported that human sperm coincubated with human peripheral
      blood neutrophils in the presence of complement (C)-fixing antisperm antibody
      (ASA)-positive sera are rapidly internalized and degraded within the neutrophil
      phagolysosome. However, the mechanism by which motile sperm are processed within
      the phagolysosome is unknown. Various spermicidal/antimicrobial proteins
      contained in azurophilic granules that can be secreted into the phagolysosome may
      play a role in sperm disposal. In this study, we examined the expression of a 37
      kDa cationic antimicrobial protein (CAP37) during sperm phagocytosis and the
      effect of its synthetic bioactive fragment, Peptide 20-44 (P20-44), on sperm
      motility, acrosomal integrity, and mitochondrial functionality. CAP37 expression
      by neutrophils undergoing ASA- and C-dependent sperm phagocytosis was increased
      as measured by flow cytometry. Exposure of motile sperm to a cationic P20-44, the
      bioactive antimicrobial fragment of CAP37, resulted in the loss of sperm motility
      without disruption of the acrosomal membrane. The sperm immobilizing activity
      (SIA) of P20-44 was modulated by the length of incubation, the concentration of
      the peptide, and the pH of the assay medium. SIA induced by P20-44 was partially
      reversible and was unaffected by the presence of anionic heparin or seminal
      plasma. Similar to the antimicrobial activity of P20-44, the SIA was also
      dependent on the presence of a disulfide bond between cysteine residues at
      positions 26 and 42 and was inhibited by Lipid A. However, the mechanism of
      action of P20-44 on sperm is not totally dependent on the molecule's cationicity,
      because five other cationic antimicrobial peptides had no detectable effect on
      sperm viability. Thus, the mechanism of action of P20-44 on human sperm is
      different from its cationic antibactericidal effect. These findings established
      that motile human sperm are sensitive to CAP37 or its synthetic bioactive peptide
      and suggested that this protein could play a role in neutrophil-mediated immune
      destruction of sperm in the female genital tract. P20-44 of CAP37 may be useful
      in investigating the regulation of human sperm motility and to construct "hybrid
      peptides" with enhanced potency as a component of vaginal contraceptive that
      could doubly be effective by killing infectious agents and inhibiting sperm
      transport.

PMID- 8575984
TI  - Selenium supplementation enhances the element concentration in blood and seminal
      fluid but does not change the spermatozoal quality characteristics in subfertile
      men.
AB  - The objective of this study was to evaluate the effect of selenium (Se)
      supplementation on Se concentration and glutathione peroxidase (GSH-Px) activity
      in blood components and seminal fluid and on spermatozoal quality characteristics
      in subfertile men. Thirty-three men were supplemented for 12 weeks with 200
      micrograms Se/day in the form of yeast-rich Se (group I, n = 16) or sodium
      selenite (group II, n = 17). Blood samples and sperm were collected at the start
      of the study and after 2, 4, 8, and 12 weeks following Se supplementation. Se
      concentration in whole blood and plasma and GSH-Px activity in red cells and
      plasma increased significantly during the study, but in the group supplemented
      with yeast-Se the effect was more pronounced. Se concentration in seminal fluid
      also increased in both groups, but the effect of yeast-Se was markedly higher
      than that of selenite. In both groups statistically significant correlations were
      found between Se concentration in plasma and seminal fluid. GSH-Px activity in
      seminal fluid in the yeast-Se group increased significantly and reached a plateau
      after 2 weeks, whereas in the selenite group the activity did not change
      throughout the whole study period. Weak correlations between Se concentrations
      and GSH-Px activities in seminal fluid were seen, but only in the yeast-Se group
      were the relations statistically significant. The subjects in both groups showed
      no response in sperm count, motility, and morphology. In conclusion, we can
      ascertain that the supplementation of subfertile men with yeast-rich Se showed a
      more pronounced effect on Se concentrations and GSH-Px activities in blood
      components and seminal fluid than selenite did. Se supplementation did not
      improve the spermatozoal quality characteristics of sperm count, motility and,
      morphology.

PMID- 8575985
TI  - Glycosidic specificity of fucosyltransferases present in rat epididymal
      spermatozoa.
AB  - We have recently demonstrated multiple fucosyltransferase (FT) activity in rat
      spermatogenic cells. To complement these findings, here we identify and partially
      characterize the glycosidic linkage specificity of FTs present in spermatozoa
      from caput and cauda epididymides. Analysis of the acceptor substrate specificity
      of the FTs by thin-layer chromatography indicated that both caput and cauda sperm
      expressed alpha(1-2)-, alpha(1-3)-, alpha(1-4)-FTs as demonstrated by fucose
      incorporation into phenyl-beta-D-galactoside, 2'-fucosyllactose, and lacto-N
      fucopentaose-I, respectively. Spermatozoa from the cauda epididymidis exhibited
      significant decreases in the levels of alpha(1-2)-, alpha(1-3)-, alpha(1-4)-FTs,
      and of total soluble FTs in comparison to spermatozoa from the caput
      epididymidis. The relative ratio of alpha(1-3)-FT to total FT activity appeared
      to be significantly higher than those of alpha(1-2)- or alpha(1-4)-FTs, in
      spermatozoa both from caput and cauda epididymides. Using different types of low
      molecular weight acceptors and the selective inhibition of the FT by N-
      ethylmaleimide, we have demonstrated that at least alpha(1-2)-FT is different
      from alpha(1-3)- or alpha(1-4)-FTs. Kinetic studies also showed that alpha(1-2)
      FT is different from alpha(1-3)- or alpha(1-4)-FTs as demonstrated by apparent Km
      and Vmax values. Moreover, alpha(1-3)- and alpha(1-4)-FT activities in cauda
      sperm were found to be highly sensitive to Mn2+ but showed differential responses
      to divalent cations. In contrast, both alpha(1-3)- and alpha(1-4)-FTs seemed to
      be relatively less sensitive to Mg2+. Thus, these results not only demonstrate
      the presence of multiple FTs in rat epididymal sperm but also differentiate
      individual FTs with regard to their kinetic properties and sensitivity to both
      inhibitor and divalent cations.

PMID- 8575986
TI  - The effect of noise trauma following training exposures in the mouse.
AB  - The effect of moderate level acoustic stimulation, or 'training', on a subsequent
      high intensity noise exposure was studied in CBA/Ca mice. Eight groups of mice
      were exposed to a variety of training paradigms as well as different intensity
      traumatic exposures. We sought a combination which would result in the maximum
      protective effect from acoustic trauma as measured by the auditory brainstem
      responses. Using a narrow band noise centered at 4.5 kHz, we investigated the
      effects of a 10-day 'interval' training regimen, allowing a rest period between
      successive training exposures, as well as several continuous training exposures.
      These training paradigms were followed by a 24 h traumatic noise exposure (also
      centered at 4.5 kHz) at one of three intensities, 107, 110, or 117 dB SPL which
      induce a temporary, a moderate, or a severe permanent threshold shift,
      respectively. In none of these trained groups was a protective effect
      demonstrated at any time up to one month following a subsequent traumatic noise
      exposure. Several groups demonstrated higher compound threshold shifts after the
      traumatic noise exposure compared to controls. After a recovery period of 4 weeks
      nearly all trained groups demonstrated a tendency toward higher permanent
      threshold shifts than the control, untrained, animals. While no protective effect
      was demonstrated, examination of the threshold shifts following the training
      periods and after the traumatic noise exposures raised interesting questions for
      future investigation regarding the inherent resistance to noise induced threshold
      shifts in the mouse.

PMID- 8575987
TI  - Cytological changes related to maturation of the organ of Corti and opening of
      Corti's tunnel.
AB  - Maturation of the organ of Corti in the gerbil was analyzed between 2 and 16 days
      after birth (DAB) by electron microscopy and immunostaining for beta-tubulin. At
      2 DAB, the organ of Corti consisted of stratified epithelium bearing immature
      sensory hair cells (HCs) and supporting cells. Maturation of OHCs and Deiters
      cells progressed in a medial-to-lateral direction and cytoskeletal development in
      inner pillar cells preceded that in outer pillar cells at the single location
      studied along the frequency-place map. Pillar cell differentiation progressed
      through a unique stage characterized by the appearance and stratification of
      structural features apparently concerned with opening of Corti's tunnel and
      subsequently showed other structural changes related to maturity toward the adult
      form. Development of the microtubule cytoskeleton occurred first in the cell's
      apex and proceeded basally. Ruffling of a middle region of the cell surface by
      microvilli appeared to promote separation between inner and outer pillar cells
      and initiate tunnel opening at 4 DAB. Proliferation of distended cisternae of
      granular reticulum evidenced proteinaceous secretion by these cells between 4 and
      8 DAB. Subsequent tunnel expansion at about 14 DAB coincided with appearance in
      outer pillar cells of tubulocisternal endoplasmic reticulum and associated Golgi
      complexes that are thought to mediate fluid and ion secretion. Sixteen days
      postnatally after disappearance of granular and tubulocisternal reticula and
      Golgi complexes and at the time of clearing of tunnel fluid, lysosomes
      interpreted as mediating catabolism of endocytosed protein congregated beneath
      the apical and apicolateral plasmalemmae of inner pillar cells. As with pillar
      cells, development of the microtubule system in Deiters cells proceeded from the
      cell's apex to base. Following differentiation of their microtubule system by 8
      DAB, Deiters cells showed expansion of Golgi cisternae between 10 and 15 DAB and
      development of tubulocisternal endoplasmic reticulum at 15 DAB. Hair cells
      possessed abundant, distinctively large mitochondria from 4 to 10 DAB. The
      subsurface cisternae matured earlier in medial as opposed to lateral outer hair
      cells. Vesicles budding from underlying cisternae appeared associated with
      development of subsurface cisternae and at 16 DAB were still observed in third
      row but not in more mature first row HCs.

PMID- 8575988
TI  - Reduction in excitability of the auditory nerve following electrical stimulation
      at high stimulus rates.
AB  - While recent studies have suggested that electrical stimulation of the auditory
      nerve at high stimulus rates (e.g., 1000 pulses/s) may lead to an improved
      detection of the fine temporal components in speech among cochlear implant
      patients, neurophysiological studies have indicated that such stimulation could
      place metabolic stress on the auditory nerve, which may lead to neural
      degeneration. To examine this issue we recorded the electrically evoked auditory
      brainstem response (EABR) of guinea pigs following acute bipolar intracochlear
      electrical stimulation using charge-balanced biphasic current pulses at stimulus
      rates varying from 100 to 1000 pulses/s and stimulus intensities ranging from
      0.16 to 1.0 microC/phase. Charge density was held constant (approximately 75
      microC cm-2 geom/phase) in those experiments. To monitor the recovery in
      excitability of the auditory nerve following this acute stimulation. EABR
      thresholds, wave I and III amplitudes and their latencies were determined for
      periods of up to 12 h following the acute stimulation. Higher stimulus rates and,
      to a lesser extent, higher intensities led to greater decrements in the post
      stimulus EABR amplitude and prolonged the recovery period. While continuous
      stimulation at 100 pulses/s induced no decrement in the EABR, stimulation at 200
      and 400 pulses/s produced an increasingly significant post-stimulus reduction of
      the EABR amplitude, which showed only partial recovery during the monitoring
      period. No EABR response could be evoked immediately following stimulation at
      1000 pulses/s, using a probe intensity 16-19 dB below the stimulus intensity.
      However, partial EABR recovery was observed for wave III following stimulation at
      the lowest stimulus intensity (0.16 microC/phase). These stimulus-induced
      reductions in the EABR amplitude were also reflected in increased thresholds and
      latencies. Providing stimulus rate and intensity were held constant, stimulation
      at different charge densities (37.7, 75.5 and 150.7 microC cm-2 geom/phase) had
      no influence on the post-stimulus EABR recovery. Significantly, the introduction
      of a 50% duty cycle into the stimulus pulse train resulted in a more rapid and
      complete post-stimulus recovery of the EABR compared to continuous stimulation.
      These data suggest that stimulus rate is a major contributor to the observed
      reduction in excitability of the electrically stimulated auditory nerve. This
      reduction may be a result of an activity-induced depletion of neural energy
      resources required to maintain homeostasis. The present findings have
      implications for the design of safe speech-processing strategies for use in
      multichannel cochlear implants.

PMID- 8575989
TI  - Development of the VIIIth nerve compound action potential evoked by low-intensity
      tone pips in the Mongolian gerbil.
AB  - Maturation of the cochlea and afferent auditory units is reflected by changes in
      VIIIth nerve compound action potential (CAP) parameters. We studied auditory
      nerve CAPs evoked by low-intensity stimuli in Mongolian gerbils (Meriones
      unguiculatus) ranging in age from 22 to 92 days after birth. The gerbil CAP
      development is characterized by marked changes in latency, threshold, and
      amplitude during the first few weeks of life. CAP latency and CAP threshold reach
      adult-like values at about 1 month of age. In contrast, the CAP amplitude
      continues to grow in size even after 2 months. This dichotomy suggests that the
      development of afferent auditory nerve function in the gerbil is preceded by
      maturation of the mechanical processes of the middle ear and cochlea.

PMID- 8575990
TI  - Genetics of age-related hearing loss in mice. II. Strain differences and effects
      of caloric restriction on cochlear pathology and evoked response thresholds.
AB  - The effects of genotype and diet on age-related hearing loss were evaluated using
      auditory brainstem response (ABR) thresholds and post-mortem cochlear
      histopathology in 5 inbred mouse strains, CBA/H-T6J (CH), DBA/2J (D2), C57BL/6J
      (B6), BALB/cByJ (BY) and WB/ReJ (WB), and their 10 F1 hybrid strains. The mice
      had been maintained since weaning on either a high-energy (HE) control diet or
      low-energy (LE) calorically restricted diet. ABR thresholds were obtained when
      the mice were 23 months old; the mice were allowed to age until they died from
      natural causes prior to obtaining the histological material. The severity of post
      mortem cochlear pathology in mice maintained with the HE diet supports our
      earlier genetic model which postulated that B6, BY, and WB strains each possessed
      a different recessive allele causing age-related hearing loss, D2 mice possessed
      all 3 genes, and CH mice possessed none. The histopathology indicates that the
      genes act at the cochlear level. Dietary restriction resulted in increased
      longevity in a number of strains, but age-related changes in cochlear pathology
      were not ameliorated in any of these; indeed, in some strains long-lived LE mice
      exhibited severe cochlear degeneration. In strains for which longevity was not
      extended by caloric restriction, only B6 mice exhibited an ameliorative effect of
      the LE diet on cochlear pathology. ABRs in 23-month-olds indicated a slowing of
      age-related hearing loss in LE mice of 3 F1 hybrid strains.

PMID- 8575991
TI  - Base-to-apex gradient of cell proliferation in the chick cochlea following
      kanamycin-induced hair cell loss.
AB  - In order to elucidate the mechanisms that drive cell proliferation in the avian
      cochlea, we investigated the spatio-temporal relationship between hair cell
      degeneration and cell proliferation after aminoglycoside ototoxicity. Neonatal
      chicks were given a daily intramuscular injection of kanamycin (KM) at 400 mg/kg
      per day for 10 consecutive days. At various times during or after KM
      administration, proliferating cells were labeled over a period of 2 days with
      bromodeoxyuridine (BrdU) and visualized with peroxidase immunohistochemistry.
      Changes in the location of the hair cell lesion during the KM treatment were
      monitored by phalloidin immunofluorescence or scanning electron microscopy. Hair
      cell loss began at the base of the cochlea 6 days after the start of KM
      injections, whereas cell proliferation was first observed in the basal region
      between days 6 and 8 of the KM treatment. This indicates that the latency between
      cell loss and cell proliferation is less than 48 h. The region of cell
      proliferation shifted from the base toward the apex of the cochlea over a period
      of 6-8 days, but cell proliferation in a specific region of the cochlea only
      occurred for 2-4 days. The latency as well as the total duration of cell
      proliferation after KM ototoxicity was virtually equivalent to that observed
      after acoustic trauma (Hashino and Salvi, 1993), suggesting that similar cellular
      events are involved in triggering cell proliferation after mechanical destruction
      and metabolic destruction of avian hair cells. The spatio-temporal gradient of
      cell proliferation followed the pattern of hair cell loss, suggesting that some
      aspect of hair cell degeneration provides trigger signals for cell proliferation.

PMID- 8575992
TI  - Structural and ultrastructural aspects of isolated immature cochlear outer hair
      cells maintained in short-term culture.
AB  - Immature outer hair cells (OHCs), isolated from developing rat cochlea without
      using proteolytic enzymes, were maintained in short-term culture in a clot of
      coagulated plasma. Cell viability was assessed by a laser scanning image
      cytometer, using double-fluorescent labeling. Light and transmission electron
      microscopy was used to study the morphology of isolated cells. Ten to 60 healthy
      OHCs were obtained from one cochlea, either as single isolated cells or clusters
      containing 2-10 cells from the same row. Although dead cells were observed only 1
      h after dissociation, there were still viable cells after 6 h. Isolated OHCs were
      not perfectly cylindrical, due to the immaturity of their cortical structures.
      One hour after dissociation the ultrastructural organization of the isolated
      cells was generally well preserved, but this was followed by dilatation of the
      Golgi apparatus and endoplasmic reticulum. Specific changes in isolated OHCs were
      also observed at the subsurface cisternae and cuticular plate. Although
      degenerating OHCs generally showed a classic pattern of necrosis, certain
      morphological features reminiscent of apoptosis were also observed. This study
      emphasises the difficulty involved in investigating isolated immature OHCs in
      vitro and provides a basis for future research into the physiological
      requirements of isolated immature OHCs.

PMID- 8575993
TI  - Hearing loss and cochlear abnormalities in the congenital hypothyroid (hyt/hyt)
      mouse.
AB  - The congenital hypothyroid (hyt/hyt) mouse has been described as having a
      homozygous recessive mutation of a single locus on chromosome 12 which results in
      significant endocrine hypofunction and retarded growth. Although a distinct
      correlation between inherited hypothyroidism and hearing loss in humans exists,
      there has been no previous evaluation of the auditory system in these mutant
      mice. We determined hearing thresholds by auditory-evoked brainstem response
      testing and noted a 40-45 dB elevation in the hyt/hyt mouse compared to
      littermate heterozygote (hyt/+) animals and normal progenitor controls BALB/cByJ
      (+/+). Conventional light microscopy was used to examine the general anatomy of
      the cochlea in these animals, and the surface structure of the organ of Corti was
      further evaluated with scanning electron microscopy. Heterozygote and normal
      control mice had no significant abnormalities of the cochlea, however the hyt/hyt
      mice displayed consistent morphologic abnormalities of the stereocilia on both
      inner and outer hair cell systems. The surrounding and supporting cells were
      identified in the cochleas of the hypothyroid mouse and control animals and
      showed no significant histologic abnormalities. The auditory, histologic, and
      ultrastructural characterization of this model provides a foundation for
      evaluating the effects of true inherited hypothyroidism on auditory pathway
      development.

PMID- 8575994
TI  - Sensorineural hearing loss alters recovery from short-term adaptation in the
      C57BL/6 mouse.
AB  - Several strains of laboratory mouse (Mus musculus) have a pattern of hearing loss
      which resembles that found in humans. The C57BL/6 strain of mouse has a genetic
      defect that results in degeneration of the organ of Corti, originating in the
      basal, high-frequency region and then proceeding apically over time. The end
      result is a severe-to-profound sensorineural hearing loss (SNHL) by 14 months of
      age. In contrast, auditory function of the CBA strain remains normal through its
      early life span then slowly declines later in life, much like that typified by
      human presbycusis. The purpose of the present study was to compare ABR (peak 5)
      forward masking recovery functions in young, normal-hearing CBA and C57BL/6 mice
      to hearing-impaired C57BL/6 mice. ABR audiograms were obtained prior to
      collecting the tone-on-tone forward masking data. Masking was defined as a 50%
      reduction in the P5 component of the ABR, elicited and masked by 12 kHz tone
      bursts, using masker/probe time delays from 0 to 100 ms. Time constants were
      computed from an exponential model fit to the recovery functions (masker level
      vs. time delay). In hearing-impaired animals there was a significant increase in
      recovery from short-term adaptation as measured by the time constants, as well as
      a significant latency shift in the P5 component. The effects of SNHL on the
      recovery of the P5 component from short-term adaptation was comparable to that
      reported behaviorally for human hearing-impaired listeners and physiologically
      from the inferior colliculus (IC) of chinchillas suffering permanent threshold
      shifts.

PMID- 8575996
TI  - Amiloride-sensitive Na+ channel-like immunoreactivity in the luminal membrane of
      some non-sensory epithelia of the inner ear.
AB  - Some non-sensory epithelia of the inner ear were examined for the localization of
      immunoreactivity to polyclonal antibodies raised against amiloride-sensitive Na+
      channels from the bovine kidney. The pre-embedding immunogold technique was used
      for this purpose. Labelings were found on the membrane of the endolymphatic
      surface of strial marginal cells, epithelial cells of spiral prominence and
      Reissner's membrane, and ampullar dark cells. In contrast, no labeling was found
      on the luminal membrane of mesothelial cells of Reissner's membrane, the cells
      lining the supra-strial perilymphatic space, transitional cells and ampullar
      ceiling cells. Since the antibodies used may also label non-selective cation
      channels and non-functional sodium channel precursors as suggested by others, it
      was not possible to determine the labelings are solely due to amiloride-sensitive
      Na+ channels. However, the observed result was consistent with the previous
      studies that amiloride blocks ion transport in strial marginal cells and the
      semicircular canal. It is therefore likely that the observed labeling includes
      amiloride-sensitive Na+ channels. These labeled ion channels in a variety of
      epithelial cells lining the endolymphatic space could be important in the inner
      ear fluid regulation.

PMID- 8575995
TI  - Sound localization in chinchillas. II. Front/back and vertical localization.
AB  - The ability of chinchillas to make front/back and vertical locus discriminations
      was examined behaviorally using a conditioned avoidance procedure. Their minimum
      audible angle for localizing single broadband noise bursts was 36 degrees for
      front/back localization and 23 degrees for vertical localization. Sound
      localization tests using filtered noise demonstrated that the signal must contain
      high frequencies in order for chinchillas to make front/back and vertical locus
      judgements and that frequencies in their highest audible octave (i.e., above 16
      kHz) contribute to localization. These results support the view that a major
      selective advantage of high-frequency hearing in mammalian evolution was its
      utility for monaural as well as binaural sound localization.

PMID- 8575997
TI  - Non-invasive assessment of otolith formation during development of the Japanese
      red-bellied newt, Cynops pyrrhogaster.
AB  - Pre-mated adult female newts and embryos have been flown on the International
      Microgravity Laboratory-2 (IML-2) Space Shuttle flight in 1994 (Wiederhold et
      al., 1992b). With the specimens available from this flight, the calcification of
      otoliths, ulna, radius and backbone of the flown larvae and adult newts were
      analyzed. The experiments presented here studied the development of the otoliths
      on the ground. Otoliths of living newts, from embryo to adult, were observed in
      situ with the application of a new X-ray and bio-imaging analyzer system. For the
      establishment of this method, newts at different developmental stages were used.
      An imaging plate temporarily stores the X-ray energy pattern at the bio-imaging
      analyzer. A latent image on the imaging plate was transformed into a digital time
      series signal with an image reader. Acquired digital information was computed
      with the image processor. The processed information was recorded on film with an
      image recorder, in order to visualize it on an enlargement computed radiograph.
      To analyze development of the otoliths, photo-stimulated luminescence level was
      detected by an image analyzer, using transmitted X-ray photons. A single clump of
      otoconia could first be seen at stage 33. Stage-36 embryos first have
      distinguishable otoliths, with the utricle in front and saccule behind. Our
      results show that this X-ray method detects the otoliths equally as well as
      sectioning. In the newt, the mandibular/maxillary bone formed before the spine.
      It is suspected that for the newt embryo, living in water, feeding becomes
      necessary prior to support of the body.

PMID- 8575998
TI  - Noise exposure alters the response of outer hair cells to ATP.
AB  - The outer hair cells (OHCs) are one target of noise-induced effects. To date
      there are few studies which examine changes in the function of OHCs induced by
      noise exposure. There is increasing evidence that ATP may be a neuromodulator
      acting on OHCs. Therefore, we examined the possibility that the response to ATP
      may be altered by low-level noise exposure. ATP was tested on cation currents
      recorded from outer hair cells (OHCs) isolated from chronic noise-exposed guinea
      pigs and compared to currents recorded from normal control animals. The whole
      cell variant of the patch-clamp technique was used. The incidence of response to
      100 microM ATP was decreased in OHCs from noise-exposed animals as compared to
      controls when normal internal and external solutions were employed. When K+ was
      substituted by N-methyl-glucamine (NMG+) in the pipette solution, there were
      significant differences in the magnitudes of ATP-evoked currents between cells
      from noise-exposed and control animals. This was observed in both normal and 20
      mM Ba2+ external solutions. In addition, the response to ATP exhibited a
      dependency on OHC length. In short OHCs (< 65 microns) from noise-exposed animals
      the magnitude of the response to ATP was significantly reduced. By contrast, the
      response in long OHCs (> 65 microns) from noise-exposed animals was increased.
      Results suggest that low-level noise exposure induces changes in OHCs which
      affect the response of the cell to ATP.

PMID- 8575999
TI  - Comparative entry of carboplatin and sucrose in endolymph in the rat cochlea.
AB  - The permeability of the perilymphatic-endolymphatic interface for carboplatin was
      determined after lateral cerebral ventricle infusion of radioactive carboplatin
      (cis-diamine[1,1-cyclobutane-1-14C-dicarboxylate]platinum) to rats. [14C]sucrose,
      a similar weight molecule was used for comparison of the kinetics in the inner
      ear fluids. 14C-radioactivity was measured in perilymph and endolymph. The rate
      of elimination of the tracers from perilymph was equivalent indicating no
      difference in transport across the blood-perilymph barrier. The transport from
      perilymph to endolymph was very restricted for both substances. The present study
      indicates that the ototoxic effect of carboplatin cannot be explained by a
      specific endolymphatic transport mechanism.

PMID- 8576001
TI  - Dihydropyridines and verapamil inhibit voltage-dependent K+ current in isolated
      outer hair cells of the guinea pig.
AB  - Dihydropyridines and verapamil are widely used as blockers of voltage-dependent
      Ca++ channels. In this work we show that these compounds can have a direct
      blocking action on a class of voltage-activated potassium channels. Voltage
      dependent whole-cell currents were recorded from isolated guinea-pig outer hair
      cells (OHCs) under conditions such that the free Ca++ concentration in both the
      internal and external solutions was minimized. A substantial Ca(++)-independent
      K+ current was revealed by this procedure. Both conventional K+ and Ca++ channel
      ligands inhibited this current. The order of potency (in terms of the half
      inhibitory concentrations (IC50) of channel inhibitors) was: nimodipine (6
      microM) > Bay K 8644 (8 microM) > verapamil (11 microM) > 4-aminopyridine (22
      microM) > nifedipine (32 microM) > quinine (49 microM) > TEA (10236 microM).
      Except for verapamil, these channel ligands reduced the size of the K+ currents
      without much alteration of the time course of the currents. In contrast,
      verapamil caused a more than 10-fold increase in the apparent inactivation rate
      of the K+ currents without significantly altering the activation of the currents.
      The observation that relatively low concentrations of calcium channel ligands can
      directly inhibit potassium currents in isolated OHCs indicates that caution
      should be taken when these pharmacological agents are used as tools for studying
      cochlear hair cell physiology.

PMID- 8576000
TI  - Tetraethylammonium effects on cochlear potentials in the guinea pig.
AB  - Voltage-dependent K+ channels in the basolateral membrane of hair cells in guinea
      pig cochlea might contribute to the non-linear current-voltage relationships in
      these hair cells and, thereby, to generation of the extracellular summating
      potential (SP). To evaluate the role of K+ channels in the generation of the SP
      the perilymphatic perfusion technique was used to introduce the K(+)-channel
      blocker tetraethylammonium (TEA) into the cochlea. Sound-evoked cochlear
      potentials were measured subsequently. Without blocking nerve activity TEA
      induced reversible shifts of the SP in the negative direction, irrespective of
      whether we recorded from scala vestibuli or scala tympani. Shifts in the negative
      direction were probably due to TEA acting directly on the afferent fibres, since
      removal of nerve activity by the potent Na(+)-channel blocker tetrodotoxin (TTX)
      prevented TEA from shifting the SP in the negative direction. Once nerve activity
      had been removed by TTX, administration of TEA caused a small decrease in the
      magnitude of the SP, both in scala vestibuli and in scala tympani, irrespective
      of its polarity. The decrease was significant for the highest test frequencies
      only (8-12 kHz), and completely reversible. The rapidly activated K+ channel in
      the inner hair cell (IHC) is probably blocked by TEA and this blocking might be
      responsible for the small decrease in magnitude of the SP. The asymmetric
      contribution from this K+ channel to the IHC's current-voltage relationship seems
      to be only partly responsible for the generation of the SP, since blocking of
      this K+ channel with TEA caused relatively small decreases in the amplitude of
      the SP. TEA did not affect the endocochlear potential.

PMID- 8576002
TI  - Diet is a risk factor in cisplatin ototoxicity.
AB  - This study demonstrates that cisplatin ototoxicity depends on dietary factors and
      correlates with decreased levels of cochlear glutathione and serum albumin. After
      12 days of injections, cisplatin (1 mg/kg body weight, s.c.) caused a small
      hearing loss in guinea pigs fed a regular, full-protein diet (9 +/- 6 dB at 8 kHz
      and 10 +/- 9 dB at 18 kHz) but a significantly higher hearing loss in animals on
      a low-protein diet (23 +/- 17 dB at 8 kHz and 32 +/- 23 dB at 18 kHz). Animals on
      the low-protein diet gained significantly less weight than those on the regular
      diet, and cisplatin treatment lowered the weight gain in both groups. The low
      protein diet also significantly reduced cochlear glutathione levels from 180 +/-
      50 to 90 +/- 21 nmol/mg protein and serum albumin from 2.32 +/- 0.04 to 1.75 +/-
      0.06 g/dl. Cisplatin treatment tended to decrease glutathione and serum albumin
      in animals on a full-protein diet but not on the low-protein diet. Renal function
      was assessed by measuring blood urea nitrogen (BUN) and serum creatinine. While
      BUN and creatinine values indicated some cisplatin-induced nephrotoxicity, there
      was no correlation with the severity of ototoxicity. Furthermore, serum platinum
      levels did not differ between animals on either diet, ruling out a potential
      influence of altered pharmacokinetics on ototoxicity. These results suggest that
      the metabolic state of the animal is a risk factor for cisplatin ototoxicity.

PMID- 8576003
TI  - The relationship between sound transfer functions and hearing levels.
AB  - The effects of individuals differences in sound transfer function (STF) from free
      sound field to the tympanic membrane on hearing levels was studied in the right
      and left ears of 55 young male and 45 young female subjects. Furthermore, canal
      volumes and lengths have been recorded. STFs were measured in 1/3-octave bands
      using a miniature microphone and an attached probe. STF measurements were
      performed in the 0.5-16 kHz frequency range. Audiograms were registered with
      linear frequency sweep from 0.25 to 8 kHz. Transfer function spectra and
      magnitudes as well as ear canal dimensions were compared to hearing levels. There
      was a significant relationship between the dimensions of the ear canal and
      hearing levels. Large, compared to small, ear canal volumes resulted in a shift
      of STFs towards lower frequencies. STF spectra and magnitudes had a significant
      effect on hearing levels. Subject with low-frequency-dominated STFs have higher
      hearing thresholds than subjects with lower magnitude STFs.

PMID- 8576004
TI  - Auditory phenotyping of heterozygous sound-responsive (+/dn) and deafness (dn/dn)
      mice.
AB  - Accurate phenotyping of offspring from backcross matings between F1 heterozygous
      sound-responsive and deafness mice is an important step for the identification of
      the deafness (dn) gene (Keats et al., 1995). Here, we report the results of
      auditory phenotyping of backcross offspring who are either sound-responsive or
      deaf by recording the Preyer reflex elicited by hand clap, auditory brainstem
      responses (ABRs), and 2f1-f2 distortion product otoacoustic emissions (DPOEs).
      Our results show that the Preyer reflex observation alone is inadequate for
      auditory phenotyping; a more precise test such as a click-evoked ABR recording is
      needed for auditory phenotyping. DPOE recording results in identification of
      sound-responsive or deaf mice as accurately as the click-evoked ABR testing. In
      addition, because the DPOE amplitude function is in good agreement with the ABR
      threshold in frequency sensitivity and specificity for stimulus frequencies
      between 1 and 16 kHz, the DPOE recording can be considered as an alternate test
      for auditory phenotyping.

PMID- 8576005
TI  - Postnatal development of the projection from the medial superior olive to the
      inferior colliculus in the rat.
AB  - Normal projection development from the medial superior olive (MSO) to the
      inferior colliculus (IC) was examined by injecting Fluoro-Gold (FG), a retrograde
      tracer, into the IC unilaterally at postnatal days 0 (P0), P3, P7 and maturity.
      The rats were killed 1 day after FG injection. At all ages, labeled neurons in
      the MSO appeared on the ipsilateral side only, as in adult controls. The total
      number of MSO neurons counted in Nissl-stained sections was constant throughout
      the postnatal periods. The labeled frequency index of MSO neurons was increased
      stepwise (from 35% to 90%) with increasing postnatal stages (from P0 to
      adulthood), suggesting differential growth of early- and late-developing axons.

PMID- 8576006
TI  - Anatomical plasticity in the medial superior olive following ablation of the
      inferior colliculus in neonatal and adult rats.
AB  - We evaluated the consequences of unilateral ablation of the inferior colliculus
      (IC) upon the ascending projection from the medial superior olive (MSO) to the
      IC. Ablation of the IC was performed in rats aged between postnatal day 1 (P1)
      and maturity. All the rats were given injections of Fluoro-Gold (FG) into the
      ipsilateral IC at birth (P0) (before the ipsilateral IC was ablated in any case)
      so that growth of early-developing axons to the ipsilateral IC could be examined
      for any labeled neurons in the ipsilateral MSO. Upon reaching adulthood, the rats
      received injections of Fluoro-Ruby (FR) into the contralateral (intact) IC so
      that aberrant crossed projections to the intact IC could be examined for any
      labeled neurons in the ipsilateral MSO. These rats were killed 2 days after FR
      injections. The number of surviving cells in the ipsilateral MSO were counted in
      Nissl-stained sections for quantitative analysis of retrograde degeneration. The
      results show that: (1) the total number of neurons was reduced to 64-34% in the
      ipsilateral MSO as a result of IC ablation; (2) cell reduction by retrograde
      degeneration followed a U-shaped curve with a maximal effect in rats operated at
      P7 (reduced to 34%); (3) adult ablation of the IC led to retrograde degeneration
      that was less severe than that in late neonatal (P7) ablation; (4) an aberrant
      projection from the MSO to the contralateral IC occurred in rats operated at P1
      and P3 but not in rats operated at P7 or maturity. Thus, our findings suggest
      that growth of late-developing axons is a major factor in the plasticity of this
      system of projection.

PMID- 8576007
TI  - Detection and quantification of endolymphatic hydrops in the guinea pig cochlea
      by magnetic resonance microscopy.
AB  - Three-dimensional magnetic resonance microscopy (MRM) was used to study normal
      and hydropic cochleae of the guinea pig. With this technique consecutive serial
      slices representing the entire volume of isolated, fixed cochleae were obtained.
      The voxels (volume elements) making up the contiguous slices were isotropic (25
      microns 3) and in each slice the boundaries of scala media, including the
      position of Reissner's membrane, were clearly delineated. Three-dimensional
      reconstructions of the endolymphatic and perilymphatic scale were generated.
      Custom software was developed to quantify cross-sectional area (CSA) of all
      scalae. In the normal cochlea all 3 scalae, including scala media, showed a
      gradual decrease in CSA from base to apex. Marked differences existed between our
      findings and previously reported cochlear dimensions, especially for the
      perilymphatic scalae in the basal turn. In hydropic cochleae the scala media was
      enlarged to a varying extent in different turns and marked changes in the degree
      of distension of Reissner's membrane occurred along the cochlea. MRM and
      subsequent computer analysis of the isotropic data provide excellent methods for
      imaging and quantifying the fluid spaces of normal and hydropic cochleae.

PMID- 8576008
TI  - Anatomical and physiological measures of auditory system in mice with peripheral
      myelin deficiency.
AB  - Animal models with genetic abnormalities have been increasingly used in auditory
      research. Both TrJ mice and Po-DT-A mice are animals with peripheral myelin
      deficiency. In TrJ mice, the defect is due to a mutated PMP-22 gene. In Po-DT-A
      mice, the defect is produced by a transgene using the rat Po promotor to direct
      the expression of gene encoding for the bacterial diphtherial toxin A chain (DT
      A). This study evaluates the auditory system both physiologically and
      histologically in these two strains of mice. Histological examination revealed
      that there was myelin deficiency of the auditory nerve fibers, accompanied by a
      loss of dendrites and a loss of spiral ganglion cell bodies in both strains of
      mice. In general, histological deficits in TrJ mice were greater than those in Po
      DT-A mice. There was a strong correlation between the degree of myelin deficiency
      and the survival of spiral ganglion neurons. ABR measurements exhibited
      differences in threshold, latency and slope of the ABR growth function between
      myelin-deficient mice and their respective controls. These results suggest that
      the integrity of the myelin in the auditory nerve is important both for neural
      survival and for normal electrophysiological function of spiral ganglion neurons.

PMID- 8576010
TI  - Decisions in a gray world.

PMID- 8576009
TI  - Electrically evoked auditory brainstem response in peripherally myelin-deficient
      mice.
AB  - The integrity of the myelin sheath is important for normal electrophysiological
      function and survival of neurons that make up the auditory nerve. It is
      hypothesized that myelin deficiency of the auditory nerve may change the
      electrophysiologic characteristics of the auditory system, especially the
      temporal properties. In this study, the electrically evoked auditory brainstem
      response (EABR) was systematically evaluated in TrJ and Po-DT-A mice. Both of
      these mice have a deficit of their peripheral myelin. Correlation between the
      EABR and degree of myelin deficiency was also evaluated. The EABR in both strains
      of poorly myelinated mice exhibited prolonged latency, decreased amplitude,
      elevated threshold of wave I evoked by short-duration stimuli (20
      microseconds/phase). A 2-pulse stimulation paradigm was used to evaluate
      refractory properties. Myelin-deficient mice exhibited slower recovery from the
      refractory state than controls. Long-duration stimuli (4 ms/phase) were used to
      assess integration properties. Myelin-deficient mice demonstrated prolonged wave
      I latency and more gradual latency changes with current level. Myelin thickness
      showed a strong correlation with EABR threshold for short-duration stimulation (r
      = -0.784), maximum wave I latency (r = -0.778) and the time constant of the wave
      I latency-current level function (r = -0.736) for long-duration stimulation and
      normalized wave I recovery functions (r = -0.718). These findings suggest that
      EABR measurement may be a promising tool to assess the electrically stimulated
      properties of auditory neurons, particularly related to the status of myelin
      sheath.

PMID- 8576011
TI  - Paying respect: care of elderly parents by Chinese and Filipino American women.
AB  - Chinese and Filipino American women's caregiving for their elderly parents was
      explored. Patterns of care, sources of stress, and resources and strategies used
      in coping with the stress and providing care were investigated using a grounded
      theory methodology. Patterns of care included "paying respect" by "caring for"
      and "providing for" elderly parents. Sources of stress were caregiving demands,
      interpersonal relationships, conflict between traditional cultural expectations
      and what the caregivers could provide, and issues of control. Resources
      identified were primarily personal, familial, and cultural. Strategies used to
      cope with the stress included optimism, trust in religion, setting limits, and
      taking charge. The phenomenon of respect for elders described in this study is
      consistent with that described by Stern et al. (1980, 1985). The satisfaction
      gained from paying respect contributed to the women's ability to integrate the
      caregiving role with other roles, congruent with Meleis's theory of role
      integration.

PMID- 8576012
TI  - Counteracting abuse and breaking free: the process of leaving revealed through
      women's voices.
AB  - In a feminist, grounded-theory study, we interviewed rural survivors of abusive
      relationships to discover a substantive theory to explain the process of leaving.
      The central process for survivors was reclaiming self. In this article, we
      discuss the initial stages of reclaiming self: counteracting abuse and breaking
      free. Our findings reveal that the abused women were not passive victims. From
      the beginning, they counteracted abuse by relinquishing parts of self, minimizing
      abuse, and fortifying their defenses. The work of counteracting abuse prepared
      the survivor for testing the exits in the process of breaking free. These
      findings support the view of abused women as survivors and clearly demonstrate
      the societal infrastructure required to support women's efforts to counteract
      abuse until they have acquired the strength and resources to leave. In addition,
      questions are raised about the roles of lay and professional helpers in
      facilitating and inhibiting the process of reclaiming self.

PMID- 8576013
TI  - Older women in Latin America: the health and socioeconomic situation of this
      important subgroup.
AB  - The social and health consequences of aging, for women in Latin America, have
      been largely unexplored. This research reports the results of a review and
      secondary analysis of existing published and unpublished data. The analytical
      framework cross-classifies the data into three categories of age: midlife (40
      59), young old (60-74), and old old (75+), and three categories of country type:
      highly rural, mixed, and highly urban. Findings revealed a group at severe
      disadvantage educationally, economically and, by virtue of their longevity,
      likely to end up widowed and suffering the physical effects of premature aging.
      Older women also bear the major burden for economic survival and emotional
      vitality of the family. The strategies they develop to respond to these
      necessities are innovative and often involve creation of new family forms based
      on cooperation among women. These deserve greater study as potential models for
      interventions to take advantage of the long-neglected ingenuity represented by
      this group.

PMID- 8576014
TI  - Attitudes toward menopause among Mexican American women.
AB  - An exploratory study was conducted to determine Mexican American women's
      attitudes toward menopause and the relationships between these attitudes and
      socioeconomic status, level of acculturation, menopausal status, symptoms, self
      esteem, and social support. The sample included 130 Mexican American women who
      ranged in age from 28 to 75 years. Attitudes did not differ by socioeconomic
      status, menopausal status, or number and severity of symptoms. More positive
      attitudes were reported by less acculturated women and women with higher self
      esteem. Menopause was perceived as a potentially disturbing transition, and
      irritability and depressive mood were expected. Findings support the need for
      more accessible information to decrease uncertainty and avert negative
      expectations.

PMID- 8576015
TI  - The impact of marital status and quality on family functioning in maternal
      chronic illness.
AB  - Married individuals tend to enjoy greater health and well-being than nonmarried.
      However, investigators disagree about whether this is related to the quality of
      the marriage or to participation in the socially accepted role of marriage. In
      the present study, we examined the roles of marital quality and marital status as
      predictors of the family's adjustment processes in the context of maternal
      chronic illness. We found that the family functioning of single women and
      unhappily married women was similar and that happily married women enjoyed higher
      levels of family functioning and family coping. Unhappily married women reported
      more illness demands, particularly on their time and energy, than did happily
      married or single women. We suggest it is the quality of the marital interaction,
      and not the role benefits of marriage, that facilitates family adjustment under
      conditions of maternal chronic illness.

PMID- 8576016
TI  - Use of a mobile health van by a vulnerable population: homeless sheltered women.
AB  - Little is known about the health status of homeless women. In this study, we
      examined the health problems of and services provided to sheltered, homeless,
      Midwestern women who used a mobile health van. Our objectives were to document
      these women's ages, self-reported past medical histories, self-reported histories
      of addictions and hospitalizations, presenting concerns, diagnoses, and visit
      patterns. To this end, we performed a retrospective review of the 689 records of
      408 women who had sought care during a 3-year period. The data were divided into
      three groups, representing women ages 15-25 (n = 111), 26-40 (n = 211), and 41-70
      (n = 86). In all three age groups, respiratory disorders were most frequently
      treated. Preventive health maintenance concerns were also major concerns of all
      age groups. Recommendations for improving the quality, continuity, and follow-up
      of care are offered.

PMID- 8576018
TI  - Understanding intimacy as experienced by breastfeeding women.
AB  - The woman who is breastfeeding her infant may experience intimacy in a variety of
      ways. The author explores some of those ways, starting with identity and the
      woman's intimacy with herself and proceeding to the woman's intimate interaction
      with her infant, partner, family, or significant friends. The characteristics
      associated with intimacy, such as reciprocity, mutual joy, harmony, concern for
      other, trust, and closeness, have all been described as part of successful
      breastfeeding experiences. Researchers have acknowledged the influence of
      emotional support on breastfeeding but have failed to recognize the dynamics of
      intimacy as other than physical or sexual. The popular concepts of intimacy as
      sexual and the breast as sexual derive from a male perspective, one that
      restrains and shapes women's attitudes toward breastfeeding. Research on this
      topic is required if professionals hope to help women and their partners to
      understand the psychosocial dynamics of breastfeeding.

PMID- 8576017
TI  - Use and effectiveness of psychological self-care strategies for interstitial
      cystitis.
AB  - We explore two questions. First, What psychological self-care strategies do women
      use to manage interstitial cystitis (IC), and how effective are they? Second, How
      do self-reported cognitive-behavioral and stress reduction activities compare
      with the coping options hypothesized by Draucker (1991) to be available to women
      diagnosed with IC? One hundred thirty-eight women with IC rated the use and
      effectiveness of 53 psychological self-care strategies as well as levels of
      uncertainty related to the illness. Findings indicated that the women used a wide
      variety of psychological self-care strategies, including information seeking,
      self-validation, rejection of pathologizing psychological explanations, and
      downward comparison to provide perspective. Even after diagnosis, most of the
      women experienced considerable uncertainty regarding changing symptoms and
      ability to predict and plan. Use and effectiveness of most psychological
      strategies appeared to be more strongly related to being involved in a support
      group, than to current status of the illness.

PMID- 8576019
TI  - Arterial embolization of post-partum hemorrhage.
AB  - The case of a 24-year-old patient with severe post-partum hemorrhage resistant to
      medical therapy is reported. Active bleeding was documented on CT and confirmed
      by angiography. Selective embolization of the cervico-uterine artery promptly
      stopped the bleeding. Selective embolization is recommended as the treatment of
      choice for intractable post-partum hemorrhage.

PMID- 8576020
TI  - Embolisation of bleeding pelvic lesions from benign origin--long-term results.
AB  - Long-term outcome and survival after emergency embolisation of life-threatening
      bleeding caused by non-malignant small pelvic lesions were analysed and related
      to the techniques and embolisation materials used. Emergency transcatheter
      embolisation was performed in 11 patients, heavily bleeding from uterine
      arteriovenous malformations (4 patients), pelvic fractures (4 patients), Endoxan
      induced cystitis (1 patient), haemorrhoids (1 patient) and polyposis recti (1
      patient) using GAW-coils. Ethibloc and Gelfoam strips as embolisation materials,
      alone or in combination. Follow-up was obtained up to 7.5 years with analysis of
      survival. Only in one patient, with terminal hepatic insufficiency and severe
      disturbance of coagulation, recurrent bleeding occurred 1 month after
      embolisation. Two other patients died during follow-up for other reasons (cardiac
      insufficiency at 17 months, ileus at 52 months). Complications in relation to the
      embolisation therapy did not occur. In conclusion, percutaneous transcatheter
      embolisation is a safe and effective procedure in severe hemorrhage resulting
      from non-malignant lesions of the pelvis.

PMID- 8576021
TI  - [Giant and bilateral renal angiomyolipomas].
AB  - We describe the very pathognomonic CT aspects of giant renal angiomyolipomas
      fortuitously demonstrated in a young male with typical neurological and
      dermatological patterns of tuberous sclerosis. Angiomyolipomas are rare but 20 to
      50% are associated with multiple sclerosis. The advent of CT has made the
      diagnosis much accurate and avoids unnecessary surgery especially for a single
      mass. The presence of fat intermixed with areas of other tissue density is very
      specific and practically excludes the diagnosis of renal carcinoma. Along with
      MRI, CT is a method of choice to delineate the sometimes very invading tumor. The
      symptoms of tuberous sclerosis are shortly reminded; the clinical presentation
      and complications of angiomyolipomas are briefly described.

PMID- 8576022
TI  - MR imaging of a diverticulum in a female urethra.
AB  - The case of a 44-year-old woman with urethral diverticulum is described. The
      lesion was initially detected by ultrasonography. MRI proved to be very sensitive
      in localising and delineating the urethral diverticulum and could differentiate
      it from lesions arising from the vagina or bladder.

PMID- 8576023
TI  - Transvaginal duplex ultrasound in oncological gynecology.
AB  - In the evaluation of the female pelvis, sonography in general complements the
      physical examination of the patient. The goal is to differentiate normal features
      from pathophysiological lesions, inflammatory processes and tumoral masses, the
      latter ones either being benign or malignant. Transvaginal sonography is now
      generally considered as a more specific and more advanced diagnostic procedure
      than abdominal sonography. The ability to assess flow to and within the pelvic
      organs and masses using Doppler, expands the contribution of transvaginal
      ultrasound to the patho-physiologic parameters. The growth of new vessels or the
      development of existing ones forms a common thread throughout many areas of
      reproductive pathophysiology. Duplex transvaginal ultrasound will allow us to
      document some events in these areas. Since unrestricted tumor growth is dependent
      upon angiogenesis, transvaginal duplex ultrasound has thus been proposed to
      enhance the ultrasound specificity for gynecological cancer. However, similar
      processes of angiogenesis and thus Doppler features, can be observed during
      normal physiological events. To avoid confusion, morphological and Doppler
      features have to be carefully combined. This paper will emphasize on the relative
      contributions of each of them and the possible pitfalls.

PMID- 8576024
TI  - Computer tomography and magnetic resonance imaging in the evaluation of bladder
      cancer.
AB  - Bladder cancer is the most common of the malignant urothelial tumours accounting
      for 6% of all male cancers, and CT and MRI are both firmly established as
      valuable methods of staging. Although MRI has important advantages compared with
      CT, the results of studies carried out in the 1980's comparing both techniques
      for staging showed a similar accuracy range (64-92% for CT and 72-96% for MRI).
      However, during recent years, advances in technology in MRI and the use of
      intravenous contrast medium have improved results, particularly in the evaluation
      of early lesions. The advantage and limitations of both techniques will be
      discussed in relation to staging of primary tumour and lymph nodes. Imaging is
      also important for the reassessment of patients following treatment to monitor
      therapeutic response and to identify recurrence. MRI may be superior to CT for
      the distinction of fibrosis and oedema from tumour following radiotherapy, but
      both techniques appear to be equally accurate in the evaluation of
      chemotherapeutic response in advanced invasive disease.

PMID- 8576025
TI  - [The significance of focal hypoechoic lesions in the peripheral zone of the
      prostate].
AB  - Hypoechoic lesions in the peripheral zone of the prostate gland are one of the
      commonest abnormalities at transrectal ultrasonography (TRUS). 90% of all
      carcinomas originating in the peripheral zone present as a hypoechoic lesion.
      Hypoechogenicity though is not specific, as many benign lesions are also
      hypoechoic. In this retrospective study, based on TRUS alone 57% of the
      hypoechoic lesions showed carcinoma in the biopsy core (43% of the biopsy cores
      were benign). The number of positive biopsies increased up to 75% when the
      hypoechoic lesion was palpable at digital rectal examination. 5.2% of the
      hypoechoic cancers would have been missed when non-palpable lesions would not
      have had a biopsy. When the hypoechoic lesion was associated with increased serum
      concentration of prostate specific antigen (PSA > 4 ng/ml) 74% of the biopsies
      were positive. 20% to 25% of all hypoechoic cancers would not have had a biopsy.
      The positive predictive value was 85% when the hypoechoic lesion was palpable at
      digital rectal examination and the PSA-concentration was > 4 ng/ml (and 90% when
      volume-adjusted PSA-parameter would have been applied).

PMID- 8576026
TI  - [Radioscopy and radiography of the thorax. Birth and maturation of an ever
      current technique].
AB  - There are three milestones in the history of thoracic radiology. Thoracic
      radiology started in 1897 when Williams developed thoracic fluoroscopy and
      introduced the basic concepts of roentgenologic interpretation. At the same time,
      the first chest films were performed allowing decisive improvement in the
      diagnosis of many chest diseases. Continuous technical improvement is responsible
      for the fact that, even today, the conventional chest film remains a highly
      accurate and frequently used imaging modality. A third milestone was the
      development of digital radiography and its use in the chest. Computerised
      tomography changed thoracic imaging dramatically; in a first step mainly as a
      tool to visualise soft tissue abnormalities and, later on, also as a modality to
      study lung disease. The recent development of the digital chest radiograph has
      again added new perspectives to the approach and diagnosis of chest disease.

PMID- 8576027
TI  - Computed tomography, magnetic resonance imaging, and digital radiography.
AB  - There are three milestones in the history of thoracic radiology. Thoracic
      radiology started in 1897 when Williams developed thoracic fluoroscopy and
      introduced the basic concepts of roentgenologic interpretation. At the same time,
      the first chest films were performed allowing decisive improvement in the
      diagnosis of many chest diseases. Continuous technical improvement is responsible
      for the fact that, even today, the conventional chest film remains a highly
      accurate and frequently used imaging modality. A third milestone was the
      development of digital radiography and its use in the chest. Computerised
      tomography changed thoracic imaging dramatically; in a first step mainly as a
      tool to visualise soft tissue abnormalities and, later on, also as a modality to
      study lung disease. The recent development of the digital chest radiograph has
      again added new perspectives to the approach and diagnosis of chest disease.

PMID- 8576028
TI  - A short history of non-vascular interventional radiology.
AB  - Interventional Radiology can be defined as minimally invasive closed percutaneous
      procedures for diagnosis or treatment and guided by imaging techniques. Parallel
      to the development of Interventional vascularRadiology, non vascular techniques
      have evolved. Margulis coined the term "Interventional Radiology" describing
      percutaneous extraction of residual gallstones. Fluoroscopy guided biopsy of the
      lung and mediastinum were described in the thorax by Nordenstrom. Percutaneous
      approach to the bile ducts was clinically applied by Wiechel, Lunderquist and
      Wallace. T-Tube extraction of residual gallstones was popularized by Burhenne.
      Cross sectional imaging, Ultrasonography and Computed Tomography offered the
      indispensable anatomical precision allowing a percutaneous approach to the deeply
      located structures in an axial plane. Haaga and Alfidi described percutaneous
      tissue sampling and drainage procedures guided by CT. Holm developed Ultrasound
      guided drainage and Otto initiated the perforated transducer. Percutaneous
      drainage of fluid collections rapidly became a standard. Plastic stents were
      inserted percutaneously in the bile ducts by Pereiras. Percutaneous neurolysis of
      the coeliac plexus was described by Hegedus Direct injection of ethanol and laser
      ablation of liver tumors, diskectomy and tubal recanalization are other more
      recently developed procedures.

PMID- 8576029
TI  - From archives to picture archiving and communications systems.
AB  - Keeping organised and consistent film archives is a well-known problem in the
      radiological world. With the introduction of digital modalities (CT, MR,...) the
      idea of archiving the image data in a non common way was born. The aim is to keep
      the information in digital form from acquisition to destination, e.g. archives,
      viewing station, teleradiology, a task that was not as easy as some people
      believed, due to bare technical possibilities and to the lack of standards
      concerning medical image data. These reasons made it not so common to integrate
      components of different origins into a digital Picture Archiving and
      Communication environment. How should we attempt to integrate the analogue
      examinations? It is ridiculous to exclude the conventional XR-examination that
      accounts for more than 70% of the total production. We believe that there will be
      a migration to light-stimulable phosphor plates, but these are not yet user
      friendly and certainly not cost effective. We have similar problems of immature
      technology as we had for the digital modalities. In a first attempt the bridge
      can be crossed, between the two worlds by means of converters (laser scanner, CCD
      camera). PACS will become a reality in the future as almost all examinations will
      be digitalized. We are now in a transition period with its inconveniences, but we
      will gain a lot soon. The migration from piles of films through a computer
      assisted radiological archiving system to a full digital environment is sketched
      in a historical survey.

PMID- 8576030
TI  - The evolution of radioprotection.
AB  - In comparison with the first half of this century the frequency of X-ray induced
      lesions diminished spectacularly both in patients and in radiologists in the
      second half; this was due to more and more rigorous radioprotection. The present
      measures of radioprotection may be divided into two groups according to their
      appliance to the patient or the operator. Prevention of irradiation of an unknown
      pregnancy is the responsibility of the clinician (application of the 10 days
      rule) but equally of the radiologist (warning poster in the radiological
      department, query of possible pregnancy). The sensitivity of the imaging material
      has been raised by adaptation of film, intensifying screens, grids and the use of
      image intensifier with TV-chain and photofluorography. The quantity of X-rays to
      the patient may be directly lowered by reducing the time and dose of fluoroscopy,
      the number of radiographs, by using a diaphragm, by covering some organs with
      lead shields and by choosing different examination modalities. Dose reduction to
      the patient may also be achieved by modifications of the quality of the X-ray
      beam (filter, KV/MA) and by proper indication of the examination. Patient's dose
      can be calculated by phantom simulation and by chromosomal blood study. The
      operator is never allowed to put his unprotected hand in the X-ray beam. The
      amount of scattering radiation to the operator will be lowered by several of the
      above mentioned measures reducing the patient's dose and by choosing the most
      favourable direction of the axis X-ray tube-image intensifier. Direct protection
      of the operator is achieved by lead-glass screens, lead flaps around the patient,
      lead gloves, apron and glasses and by raising the distance between the operator
      and the X-ray tube. Early detection of unusual radiation is possible by
      systematic dosimetry.

PMID- 8576031
TI  - Diagnostic radiology better images--lower dose compromise or correlation? A
      European strategy with historical overview.
AB  - Quality Criteria for diagnostic radiographic images include the definition of
      necessary image details, performance of the imaging system and appropriate choice
      of radiographic parameters. Actions have established a framework for the
      optimisation of these three groups of Quality Criteria. Their evolution, practice
      and efficacy will be demonstrated for conventional and digital radiology. The
      link between the Quality Criteria and exposure of the patient and staff will be
      discussed. The historical follow up of these aspects will appreciate the efforts
      done all over Europe since the twenties and will reveal the potential for
      continuously optimising diagnostic radiology in many respects: in day-to-day
      practice, new technical design and radiological concepts.

PMID- 8576032
TI  - Ribose catabolism of Escherichia coli: characterization of the rpiB gene encoding
      ribose phosphate isomerase B and of the rpiR gene, which is involved in
      regulation of rpiB expression.
AB  - Escherichia coli strains defective in the rpiA gene, encoding ribose phosphate
      isomerase A, are ribose auxotrophs, despite the presence of the wild-type rpiB
      gene, which encodes ribose phosphate isomerase B. Ribose prototrophs of an rpiA
      genetic background were isolated by two different approaches. Firstly,
      spontaneous ribose-independent mutants were isolated. The locus for this lesion,
      rpiR, was mapped to 93 min on the linkage map, and the gene order zje::Tn10-rpiR
      mel-zjd::Tn10-psd-purA was established. Secondly, ribose prototrophs resulted
      from the cloning of the rpiB gene on a multicopy plasmid. The rpiB gene resided
      on a 4.6-kbp HindIII-EcoRV DNA fragment from phage lambda 10H5 (642) of the
      Kohara gene library and mapped at 92.85 min. Consistent with this map position,
      the cloned DNA fragment contained two divergent open reading frames of 149 and
      296 codons, encoding ribose phosphate isomerase B (molecular mass, 16,063 Da) and
      a negative regulator of rpiB gene expression, RpiR (molecular mass, 32,341 Da),
      respectively. The 5' ends of rpiB- and rpiR-specified transcripts were located by
      primer extension analysis. No significant amino acid sequence similarity was
      found between ribose phosphate isomerases A and B, but ribose phosphate isomerase
      B exhibited high-level similarity to both LacA and LacB subunits of the galactose
      6-phosphate isomerases of several gram-positive bacteria. Analyses of strains
      containing rpiA, rpiB, or rpiA rpiB mutations revealed that both enzymes were
      equally efficient in catalyzing the isomerization step in either direction and
      that the construction of rpiA rpiB double mutants was a necessity to fully
      prevent this reaction.

PMID- 8576033
TI  - Coordinate genetic regulation of glycogen catabolism and biosynthesis in
      Escherichia coli via the CsrA gene product.
AB  - The carbon storage regulator gene, csrA, encodes a factor which negatively
      modulates the expression of the glycogen biosynthetic gene glgC by enhancing the
      decay of its mRNA (M. Y. Liu, H. Yang, and T. Romeo, J. Bacteriol. 177:2663-2672,
      1995). When endogenous glycogen levels in isogenic csrA+ and csrA::kanR strains
      were quantified during the growth curve, both the rate of glycogen accumulation
      during late exponential or early stationary phase and its subsequent rate of
      degradation were found to be greatly accelerated by the csrA::kanR mutation. The
      expression of the biosynthetic genes glgA (glycogen synthase) and glgS was
      observed to be negatively modulated via csrA. Thus, csrA is now known to control
      all of the known glycogen biosynthetic genes (glg), which are located in three
      different operons. Similarly, the expression of the degradative enzyme glycogen
      phosphorylase, which is encoded by glgY, was found to be negatively regulated via
      csrA in vivo. The in vitro transcription-translation of glgY was also
      specifically inhibited by the purified CsrA gene product. These results
      demonstrate that localization of glycogen biosynthetic and degradative genes
      within the Escherichia coli glgCAY operon facilitates their coordinate genetic
      regulation, as previously hypothesized (T. Romeo, A. Kumar, and J. Preiss, Gene
      70:363-376, 1988). The csrA gene did not affect glycogen debranching enzyme,
      which is now shown to be encoded by the gene glgX.

PMID- 8576034
TI  - Membrane-associated methane monooxygenase from Methylococcus capsulatus (Bath).
AB  - An active preparation of the membrane-associated methane monooxygenase (pMMO)
      from Methylococcus capsulatus Bath was isolated by ion-exchange and hydrophobic
      interaction chromatography using dodecyl beta-D-maltoside as the detergent. The
      active preparation consisted of three major polypeptides with molecular masses of
      47,000, 27,000, and 25,000 Da. Two of the three polypeptides (those with
      molecular masses of 47,000 and 27,000 Da) were identified as the polypeptides
      induced when cells expressing the soluble MMO are switched to culture medium in
      which the pMMO is expressed. The 27,000-Da polypeptide was identified as the
      acetylene-binding protein. The active enzyme complex contained 2.5 iron atoms and
      14.5 copper atoms per 99,000 Da. The electron paramagnetic resonance spectrum of
      the enzyme showed evidence for a type 2 copper center (g perpendicular = 2.057, g
      parallel = 2.24, and magnitude of A parallel = 172 G), a weak high-spin iron
      signal (g = 6.0), and a broad low-field (g = 12.5) signal. Treatment of the pMMO
      with nitric oxide produced the ferrous-nitric oxide derivative observed in the
      membrane fraction of cells expressing the pMMO. When duroquinol was used as a
      reductant, the specific activity of the purified enzyme was 11.1 nmol of
      propylene oxidized.min-1.mg of protein-1, which accounted for approximately 30%
      of the cell-free propylene oxidation activity. The activity was stimulated by
      ferric and cupric metal ions in addition to the cytochrome b-specific inhibitors
      myxothiazol and 2-heptyl-4-hydroxyquinoline-N-oxide.

PMID- 8576035
TI  - Isolation and expression of the Rhodobacter sphaeroides gene (pgsA) encoding
      phosphatidylglycerophosphate synthase.
AB  - The Rhodobacter sphaeroides pgsA gene (pgsARs), encoding
      phosphatidylglycerophosphate synthase (PgsARs), was cloned, sequenced, and
      expressed in both R. sphaeroides and Escherichia coli. As in E. coli, pgsARs is
      located immediately downstream of the uvrC gene. Comparison of the deduced amino
      acid sequences revealed 41% identity and 69% similarity to the pgsA gene of E.
      coli, with similar homology to the products of the putative pgsA genes of several
      other bacteria. Comparison of the amino acid sequences of a number of enzymes
      involved in CDP-diacylglycerol-dependent phosphatidyltransfer identified a highly
      conserved region also found in PgsARs. The pgsARs gene carried on multicopy
      plasmids was expressed in R. sphaeroides under the direction of its own promoter,
      the R. sphaeroides rrnB promoter, and the E. coli lac promoter, and this resulted
      in significant overproduction of PgsARs activity. Expression of PgsARs activity
      in E. coli occurred only with the E. coli lac promoter. PgsARs could functionally
      replace the E. coli enzyme in both a point mutant and a null mutant of E. coli
      pgsA. Overexpression of PgsARs in either E. coli or R. sphaeroides did not have
      dramatic effects on the phospholipid composition of the cells, suggesting
      regulation of the activity of this enzyme in both organisms.

PMID- 8576036
TI  - Molecular analysis of the amy gene locus of Thermoanaerobacterium
      thermosulfurigenes EM1 encoding starch-degrading enzymes and a binding protein
      dependent maltose transport system.
AB  - A gene of Thermoanaerobacterium thermosulfurigenes EM1 encoding a protein with
      similarity to the maltose-binding protein of Escherichia coli was cloned and
      sequenced. It was located in the amy gene region of the chromosome downstream of
      the pullulanase-encoding amyB gene and upstream of amyDC, encoding membrane
      components of an ABC transport system, and the alpha-amylase gene amyA. The gene
      was designated amyE. Analysis of mRNA by Northern (RNA) blotting revealed that
      expression of the amy gene region is repressed during growth on glucose. Maximum
      levels of mRNA were detected with maltose as a substrate. An operon which was
      transcribed in the order amyBEDC was identified. However, an additional
      transcription start point was found in front of amyE. The amyA gene represented a
      monocistronic operon. Putative -35 and -10 promoter sites were deduced from the
      three transcription start sites of the amy gene region, and possible regulatory
      regions mediating induction by maltose and catabolite repression by glucose were
      identified by sequence analysis and comparison. The biochemical characterization
      of maltose uptake in T. thermosulfurigenes EM1 revealed two transport systems
      with Km values of 7 microM (high affinity) and 400 microM (low affinity). We
      conclude that the high-affinity system, which is specific for maltose and
      maltotriose, is a binding-protein-dependent transporter encoded by amyEDC. The
      gene for the putative ATP-binding protein has not yet been identified, and in
      contrast to similar systems in other bacteria, it is not located in the immediate
      vicinity of the chromosome.

PMID- 8576037
TI  - Galactofuranose biosynthesis in Escherichia coli K-12: identification and cloning
      of UDP-galactopyranose mutase.
AB  - We have cloned two open reading frames (orf6 and orf8) from the Escherichia coli
      K-12 rfb region. The genes were expressed in E. coli under control of the T7lac
      promoter, producing large quantities of recombinant protein, most of which
      accumulated in insoluble inclusion bodies. Sufficient soluble protein was
      obtained, however, for use in a radiometric assay designed to detect UDP
      galactopyranose mutase activity (the conversion of UDP-galactopyranose to UDP
      galactofuranose). The assay is based upon high-pressure liquid chromatography
      separation of sugar phosphates released from both forms of UDP-galactose by
      phosphodiesterase treatment. The crude orf6 gene product converted UDP-[alpha-D-U
      14C]-galactopyranose to a product which upon phosphodiesterase treatment gave a
      compound with a retention time identical to that of synthetic alpha
      galactofuranose-1-phosphate. No mutase activity was detected in extracts from
      cells lacking the orf6 expression plasmid or from orf8-expressing cells. The orf6
      gene product was purified by anion-exchange chromatography and hydrophobic
      interaction chromatography. Both the crude extract and the purified protein
      converted 6 to 9% of the UDP-galactopyranose to the furanose form. The enzyme was
      also shown to catalyze the reverse reaction; in this case an approximately 86%
      furanose-to-pyranose conversion was observed. These observations strongly suggest
      that orf6 encodes UDP-galactopyranose mutase (EC 5.4.99.9), and we propose that
      the gene be designated glf accordingly. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of purified UDP-galactopyranose mutase revealed one major band,
      and analysis by electrospray mass spectrometry indicated a single major species
      with a molecular weight of 42,960 +/- 8, in accordance with that calculated for
      the Glf protein. N-terminal sequencing revealed that the first 15 amino acids of
      the recombinant protein corresponded to those expected from the published
      sequence. UV-visible spectra of purified recombinant enzyme indicated that the
      protein contains a flavin cofactor, which we have identified as flavin adenine
      dinucleotide.

PMID- 8576038
TI  - Distinct roles of the N-terminal and C-terminal precursor domains in the
      biogenesis of the Bordetella pertussis filamentous hemagglutinin.
AB  - The 220-kDa Bordetella pertussis filamentous hemagglutinin (FHA) is the major
      exported protein found in culture supernatants. The structural gene of FHA has a
      coding potential for a 367-kDa protein, and the mature form constitutes the N
      terminal 60% of the 367-kDa precursor. The C-terminal domain of the precursor was
      found to be important for the high-level secretion of full-length FHA but not of
      truncated analogs (80 kDa or less). The secretion of full-length and truncated
      FHA polypeptides requires the presence of the approximately 100-amino-acid N
      terminal domain and the outer membrane protein FhaC, homologous to the N-terminal
      domains of the Serratia marcescens and Proteus mirabilis hemolysins and their
      accessory proteins, respectively. By analogy to these hemolysins, it is likely
      that the N-terminal domain of the FHA precursor interacts, directly or
      indirectly, with the accessory protein during FHA biogenesis. However,
      immunogenicity and antigenicity studies suggest that the N-terminal domain of FHA
      is masked by its C-terminal domain and therefore should not be available for its
      interactions with FhaC. These observations suggest a model in which the C
      terminal domain of the FHA precursor may play a role as an intramolecular
      chaperone to prevent premature folding of the protein. Both heparin binding and
      hemagglutination are expressed by the N-terminal half of FHA, indicating that
      this domain contains important functional regions of the molecule.

PMID- 8576039
TI  - Expression and localization of HrpA1, a protein of Xanthomonas campestris pv.
      vesicatoria essential for pathogenicity and induction ofthe hypersensitive
      reaction.
AB  - The hrp cluster of the pepper and tomato pathogen Xanthomonas campestris pv.
      vesicatoria is required for both pathogenicity on susceptible host plants and
      induction of the hypersensitive reaction on resistant plants. The hrpA locus is
      located at the left end of the 25-kb hrp region and encodes a single 64-kDa Hrp
      protein, HrpA1, which belongs to the PulD superfamily of proteins involved in
      type II and type III protein secretion. In this study, we developed a defined
      medium without any plant-derived molecules that induces expression of hrpA in
      vitro. The hrpA transcription start site was mapped in the coding region of the
      hrpB8 gene, which is the last gene of the hrpB operon. The inducible hrpA
      promoter shows no homology to known promoter elements or other hrp loci of X.
      campestris pv. vesicatoria. hrpA expression was shown to be independent of the
      hrp regulatory gene hrpX. The amino acid sequence of the HrpA1 protein is
      predicted to contain an N-terminal signal sequence and no further transmembrane
      domains and to be rich in beta-sheet stretches. Expression of HrpA1 in
      Escherichia coli cells causes induction of the psp operon like some of its
      counterparts, suggesting some commonality of function and that HrpA1 forms
      multimers. The protein product of hrpA1 was identified by using a specific
      polyclonal antibody. Cell fractionation studies demonstrated that the HrpA1
      protein is localized in the outer membrane of X. campestris pv. vesicatoria.
      HrpA1 is the first component of the Hrp secretion system whose localization has
      been determined in the original organism.

PMID- 8576040
TI  - Characterization of Brucella abortus and Brucella melitensis native haptens as
      outer membrane O-type polysaccharides independent from the smooth
      lipopolysaccharide.
AB  - Brucella native haptens (NHs) extracted with hot water from smooth (S)-type B.
      abortus and B. melitensis were purified to high levels of serological activity
      and compared with the polysaccharide obtained by acid hydrolysis (PS) of the S
      lipopolysaccharide (S-LPS). By 13C nuclear magnetic resonance analysis, NHs
      showed the spectrum of a homopolymer of alpha-1,2- or alpha-1,2- plus alpha-1,3
      linked 4-formamido-4,6-dideoxy-D-mannose (N-formylperosamine) previously reported
      for the LPS O chain. However, while PS contained up to 0.6% 3-deoxy-D-manno-2
      octulosonate, this LPS-core marker was absent from NH. High performance liquid
      chromatography and thin-layer chromatography showed heterogeneity in NH purified
      from whole cells but not in PS. By immunoprecipitation, polysaccharides
      indistinguishable from NH were demonstrated in extracts obtained with phenol
      water, saline at 60 degrees C, and ether-water treatments, and none of these
      treatments caused S-LPS hydrolysis detectable with antibodies to the O chain and
      lipid A. Two lines of evidence showed that NH was in the cell surface. First, NH
      became biotinylated when B. abortus live cells were labelled with biotin
      hydrazide, and the examination of cell fractions and electron microscopy sections
      with streptavidin-peroxidase and streptavidin-coloidal gold, respectively, showed
      that labelling was extrinsic. Moreover, whereas only traces of NH were found in
      cytosols, the amount of NH was enriched in cell envelopes and in the outer
      membrane blebs spontaneously released by brucellae during growth. Interactions
      between NH and S-LPS were observed in crude cell extracts, and such interactions
      could be reconstituted by using purified NH and LPS. The results demonstrate that
      NH is not a hydrolytic product of S-LPS and suggest a model in which LPS
      independent O-type polysaccharides (NH) are intertwined with the O chain in the
      outer membrane of S-type brucellae.

PMID- 8576042
TI  - hrcA, the first gene of the Bacillus subtilis dnaK operon encodes a negative
      regulator of class I heat shock genes.
AB  - Whereas in Escherichia coli only one heat shock regulon is transiently induced by
      mild heat stress, for Bacillus subtilis three classes of heat shock genes
      regulated by different mechanisms have been described. Regulation of class I heat
      shock genes (dnaK and groE operons) involves an inverted repeat (CIRCE element)
      which most probably serves as an operator for a repressor. Here, we report on the
      analyses of an hrcA null mutant (delta hrcA), in which hrcA, the first gene of
      the dnaK operon, was deleted from the B. subtilis chromosome. This strain was
      perfectly viable at low and high temperatures. Transcriptional analysis of the
      deletion mutant revealed a high level of constitutive expression of both the dnaK
      and groE operons even at a low temperature. A further increase in the amount of
      groE transcript was observed after temperature upshift, suggesting a second
      induction mechanism for this operon. Overproduction of HrcA protein from a second
      copy of hrcA derived from a plasmid (phrcA+) in B. subtilis wild-type and delta
      hrcA strains prevented heat shock induction of the dnaK and groE operons at the
      level of transcription almost completely and strongly reduced the amounts of mRNA
      at a low temperature as well. Whereas the wild-type strain needed 4 h to resume
      growth after temperature upshift, the delta hrcA strain stopped growth only for
      about 1 h. Overproduction of HrcA protein prior to a heat shock almost completely
      prevented growth at a high temperature. These data clearly demonstrate that the
      hrcA product serves as a negative regulator of class I heat shock genes.

PMID- 8576041
TI  - Genetic analysis of the interaction between Vibrio cholerae transcription
      activator ToxR and toxT promoter DNA.
AB  - Expression of many virulence genes in Vibrio cholerae is under the control of the
      ToxT protein. These include genes whose products are required for the biogenesis
      of the toxin-coregulated pilus, accessory colonization factor, and cholera toxin.
      ToxT is a member of the AraC family of transcriptional activators and is part of
      the ToxR regulatory cascade. ToxR is a transmembrane DNA-binding protein that is
      required for transcription of toxT and also can directly activate transcription
      of the cholera toxin operon (ctxAB). The sequences upstream of ctxAB and toxT to
      which ToxR binds show no obvious similarity, which implies that ToxR may be
      recognizing a degenerate sequence or, alternatively, a common structural motif
      within both binding sites. Data presented in this report demonstrate that
      nucleotides within the upstream half-site of an inverted repeat element in the
      toxT promoter are critical for ToxR-regulated activation of transcription in V.
      cholerae. In addition, gene fusion and DNA-binding studies with mutant ToxR
      proteins indicate that residues of ToxR required for binding to the ctx promoter
      are also required for binding to the toxT promoter. These data suggest that ToxR
      is not recognizing an inverted repeat sequence per se in the activation of toxT
      but, rather, some motif composed in part of sequences within the upstream half
      site of the inverted repeat and that ToxR recognizes similar motifs within the
      ctxAB and toxT promoters.

PMID- 8576043
TI  - Effect of microaerophilic cell growth conditions on expression of the aerobic
      (cyoABCDE and cydAB) and anaerobic (narGHJI, frdABCD, and dmsABC) respiratory
      pathway genes in Escherichia coli.
AB  - Escherichia coli varies the synthesis of many of its respiratory enzymes in
      response to oxygen availability. These enzymes include cytochrome o oxidase
      (cyoABCDE) and cytochrome d oxidase (cydAB), used during aerobic cell growth, and
      a fumarate reductase (frdABCD), dimethyl sulfoxide/trimethylamine oxide reductase
      (dmsABC), and nitrate reductase (narGHJI), used during anaerobic respiratory
      conditions. To determine how different levels of oxygen affect the expression of
      each operon, strains containing cyo-lacZ, cyd-lacZ, frdA-lacZ, dmsA-lacZ, and
      narG-lacZ fusions were grown in continuous culture at various degrees of air
      saturation. The basal-level expression of the anaerobic respiratory genes,
      frdABCD, dmsABC, and narGHJI, occurred when the air saturation of the medium was
      above 20%; as the saturation was reduced to below 10% (ca. 2% oxygen), the
      expression rapidly increased and reached a maximal level at 0% air. In contrast,
      cyoABCDE gene expression was lowest under anaerobic conditions while cyd-lacZ
      expression was about 40% of its maximum level. When the oxygen level was raised
      into the microaerophilic range (ca. 7% air saturation) cyd-lacZ expression was
      maximal while cyo-lacZ expression was elevated by about fivefold. As the air
      level was raised to above 20% saturation, cyd-lacZ expression fell to a basal
      level while cyo-lacZ expression was increased to its maximum level. The role of
      the Fnr and ArcA regulatory proteins in this microaerophilic control of
      respiratory gene expression was documented: whereas Fnr function as an
      aerobic/anaerobic switch in the range of 0 to 10% air saturation, ArcA exerted
      its control in the 10 to 20% range. These two transcriptional regulators
      coordinate the hierarchial control of respiratory pathway gene expression in E.
      coli to ensure the optimal use of oxygen in the cell environment.

PMID- 8576044
TI  - Three functions of bacteriophage P1 involved in cell lysis.
AB  - Amber and deletion mutants were used to assign functions in cell lysis to three
      late genes of bacteriophage P1. Two of these genes, lydA and lydB of the dar
      operon, are 330 and 444 bp in length, respectively, with the stop codon of lydA
      overlapping the start codon of lydB. The third, gene 17, is 558 bp in length and
      is located in an otherwise uncharacterized operon. A search with the predicted
      amino acid sequence of LydA for secondary motifs revealed a holin protein-like
      structure. Comparison of the deduced amino acid sequence of gene 17 with
      sequences of proteins in the SwissProt database revealed homologies with the
      proteins of the T4 lysozyme family. The sequence of lydB is novel and exhibited
      no known extended homology. To study the effect of gp17, LydA, and LydB in vivo,
      their genes were cloned in a single operon under the control of the inducible T7
      promoter, resulting in plasmid pAW1440. A second plasmid, pAW1442, is identical
      to pAW1440 but has lydB deleted. Induction of the T7 promoter resulted in a rapid
      lysis of cells harboring pAW1442. In contrast, cells harboring pAW1440 revealed
      only a small decrease in optical density at 600 nm compared with cells harboring
      vector alone. The rapid lysis phenotype in the absence of active LydB suggests
      that this novel protein might be an antagonist of the holin LydA.

PMID- 8576045
TI  - Physical map of the genome of Vibrio cholerae 569B and localization of genetic
      markers.
AB  - A combined physical and genetic map of the genome of the classical O1
      hypertoxinogenic strain 569B of Vibrio cholerae has been constructed. The enzymes
      NotI, SfiI and CeuI generated DNA fragments of suitable size distribution that
      could be resolved by pulsed-field gel electrophoresis. The digests produced 37,
      22, and 7 fragments, respectively. The CeuI maps of the genomes of strains 569B
      and O395, constructed by partial restriction digestion, were identical, and the
      data are consistent with the concept of circular chromosomes. The genome size of
      each of the strains was estimated to be about 3.2 Mb. The NotI and SfiI digestion
      profiles of the genomic DNAs of strains 569B and O395 exhibited distinct
      restriction fragment length polymorphism. The linkages between the 37 NotI
      fragments of the genome of strain 569B were determined by combining three
      approaches: isolation of linking clones, analysis of partial digestion fragments,
      and identification of NotI fragments in isolated CeuI and SfiI fragments. To
      align linked fragments precisely, NotI-digested genomic DNA was end labeled and
      separated in the same gel with the NotI-digested DNA to be probed with linking
      clones. This also allowed the identification of smaller restriction fragments
      that are not visible in ethidium bromide-stained gels. The presence of repetitive
      DNA sequences in the V. cholerae 569B genome has been demonstrated. Twenty cloned
      homologous and heterologous genes and seven rrn operons have been positioned on
      the physical map. The two copies of the Ctx genetic element in the genome of
      strain 569B are located about 1,000 kb apart.

PMID- 8576046
TI  - Effect of the surface composition of motile Escherichia coli and motile
      Salmonella species on the direction of galvanotaxis.
AB  - We have reported that motile Escherichia coli K-12 placed in an electric field
      swims toward the anode but that motile Salmonella typhimurium strains swim toward
      the cathode, a phenomenon called galvanotaxis (J. Adler and W. Shi, Cold Spring
      Harbor Symp. Quant. Biol. 53:23-25, 1988). In the present study, we isolated
      mutants with an altered direction of galvanotaxis. By further analyses of these
      mutants and by examination of E. coli and Salmonella strains with altered cell
      surface structure, we have now established a correlation between the direction of
      galvanotaxis and the surface structure of the cell: motile rough bacteria (that
      is, those without O polysaccharide; for example, E. coli K-12 and S. typhimurium
      mutants of classes galE and rfa) swam toward the anode, whereas motile smooth
      bacteria (that is, those with O polysaccharide; for example, wild-type S.
      typhimurium LT2) swam toward the cathode. However, smooth bacteria with acidic
      polysaccharide capsules (K1 in E. coli and Vi in Salmonella typhi) swam toward
      the anode. Measurements of passive electrophoretic mobility of strains
      representative of each set were made. We propose that the different directions of
      galvanotaxis of rough (or capsulate) bacteria and of smooth bacteria are
      explicable if the negative electrophoretic mobility of flagellar filaments is
      less than that of rough bodies but greater than that of smooth bodies.

PMID- 8576047
TI  - Further genetic analysis of the activation function of the TyrR regulatory
      protein of Escherichia coli.
AB  - Previous reports (J. Cui and R. L. Somerville, J. Bacteriol. 175:1777-1784, 1993;
      J. Yang, H. Camakaris, and A. J. Pittard, J. Bacteriol. 175:6372-6375, 1993) have
      identified a number of amino acids in the N-terminal domain of the TyrR protein
      which are critical for activation of gene expression but which play no role in
      TyrR-mediated repression. These amino acids were clustered in a single region
      involving positions 2, 3, 5, 7, 9, 10, and 16. Using random and site-directed
      mutagenesis, we have identified an additional eight key amino acids whose
      substitution results in significant or total loss of activator function. All of
      these are located in the N-terminal domain of TyrR. Alanine scanning at these
      eight new positions and at five of the previously identified positions for which
      alanine substitutions had not been obtained has identified three amino acids
      whose side chains are critical for activation, namely, D-9, R-10, and D-103.
      Glycine at position 37 is also of critical importance. Alanine substitutions at
      four other positions (C-7, E-16, D-19, and V-93) caused partial but significant
      loss of activation, indicating that the side chains of these amino acids also
      play a contributing role in the activation process.

PMID- 8576049
TI  - Analysis of the Pseudomonas aeruginosa elastase (lasB) regulatory region.
AB  - The enzyme elastase is an important virulence factor of the opportunistic human
      pathogen Pseudomonas aeruginosa. Previous studies have shown that expression of
      the P. aeruginosa elastase gene (lasB) requires both an activator protein, LasR,
      and an N-acylhomoserine lactone compound termed Pseudomonas autoinducer (PAI). In
      this study, we analyzed the lasB promoter region to learn more about lasB
      activation by LasR and PAI. We report that the lasB transcriptional start is
      located 141 nucleotides upstream from the lasB translational start. It was also
      discovered that the lasB promoter region contains two putative operator sequences
      (OP1 and OP2) that are similar to each other and the Vibrio fischeri lux
      operator. OP1 is located directly upstream from, and may overlap with, the lasB
      promoter region, and OP2 is centered 102 nucleotides upstream from the lasB
      transcriptional start site. To study the effects of these putative operators and
      other sequences upstream from the lasB transcriptional start site on lasB
      activation, a series of transcriptional lasBp-lacZ gene fusions was constructed.
      Data from these fusions indicate that both putative operators are involved in
      LasR- and PAI-mediated lasB activation, with OP1 being more important than OP2.

PMID- 8576048
TI  - Identification of a site in the phosphocarrier protein, HPr, which influences its
      interactions with sugar permeases of the bacterial phosphotransferase system:
      kinetic analyses employing site-specific mutants.
AB  - The permeases of the Escherichia coli phosphoenolpyruvate:sugar
      phosphotransferase system (PTS), the sugar-specific enzymes II, are energized by
      sequential phosphoryl transfer from phosphoenolpyruvate to (i) enzyme I, (ii) the
      phosphocarrier protein HPr, (iii) the enzyme IIA domains of the permeases, and
      (iv) the enzyme IIBC domains of the permeases which transport and phosphorylate
      their sugar substrates. A number of site-specific mutants of HPr were examined by
      using kinetic approaches. Most of the mutations exerted minimal effects on the
      kinetic parameters characterizing reactions involving phosphoryl transfer from
      phospho-HPr to various sugars. However, when the well-conserved aspartyl 69
      residue in HPr was changed to a glutamyl residue, the affinities for phospho-HPr
      of the enzymes II specific for mannitol, N-acetylglucosamine, and beta-glucosides
      decreased markedly without changing the maximal reaction rates. The same mutation
      reduced the spontaneous rate of phosphohistidyl HPr hydrolysis but did not appear
      to alter the rate of phosphoryl transfer from phospho-enzyme I to HPr. When the
      adjacent glutamyl residue 70 in HPr was changed to a lysyl residue, the Vmax
      values of the reactions catalyzed by the enzymes II were reduced, but the Km
      values remained unaltered. Changing this residue to alanine exerted little
      effect. Site-specific alterations in the C terminus of the beta-glucoside enzyme
      II which reduced the maximal reaction rate of phosphoryl transfer about 20-fold
      did not alter the relative kinetic parameters because of the aforementioned
      mutations in HPr. Published three-dimensional structural analyses of HPr and the
      complex of HPr with the glucose-specific enzyme IIA (IIAGlc) (homologous to the
      beta-glucoside and N-acetylglucosamine enzyme IIA domains) have revealed that
      residues 69 and 70 in HPr are distant from the active phosphorylation site and
      the IIAGlc binding interface in HPr. The results reported therefore suggest that
      residues D-69 and E-70 in HPr play important roles in controlling conformational
      aspects of HPr that influence (i) autophosphohydrolysis, (ii) the interaction of
      this protein with the sugar permeases of the bacterial phosphotransferase system,
      and (iii) catalysis of phosphoryl transfer to the IIA domains in these permeases.

PMID- 8576050
TI  - Suppression of ftsH mutant phenotypes by overproduction of molecular chaperones.
AB  - Decreased intracellular levels of FtsH, a membrane-bound ATPase, led to
      retardation of growth and protein export, as well as to an abnormal translocation
      of alkaline phosphatase that had been attached to a cytoplasmic domain of a
      multispanning membrane protein, SecY. The last phenotype is designated Std (stop
      transfer defective). In this study, we examined the effects of overproduction of
      some molecular chaperones on the phenotypes of ftsH mutants. The growth
      retardation was partially suppressed by overproduction of GroEL/GroES
      (Hsp60/Hsp10) or HtpG (Hsp90), although these chaperones could not totally
      substitute for FtsH. Overproduction of HtpG specifically alleviated the Std
      phenotype, while that of GroEL/GroES alleviated the protein export defect of ftsH
      mutants. These results suggest that FtsH functions can be somehow compensated for
      when the cellular concentrations of some molecular chaperones increase.

PMID- 8576051
TI  - Characterization of degQ and degS, Escherichia coli genes encoding homologs of
      the DegP protease.
AB  - The degQ and degS genes of Escherichia coli encode proteins of 455 and 355
      residues, respectively, which are homologs of the DegP protease. The purified
      DegQ protein has the properties of a serine endoprotease and is processed by the
      removal of a 27-residue amino-terminal signal sequence. A plasmid expressing degQ
      rescues the temperature-sensitive phenotype of a strain bearing the degP41
      deletion, implying that DegQ, like DegP, functions as a periplasmic protease in
      vivo. Deletions in the degQ gene cause no obvious growth defect, while those in
      the degS gene result in a small-colony phenotype. The latter phenotype is rescued
      by a plasmid expressing the degS gene but not by plasmids expressing the degQ or
      degP genes. This result and the inability of a plasmid expressing degS to rescue
      the temperature-sensitive degP41 phenotype indicate that the DegS protein is
      functionally different from the DegQ and DegP proteins.

PMID- 8576053
TI  - CWH41 encodes a novel endoplasmic reticulum membrane N-glycoprotein involved in
      beta 1,6-glucan assembly.
AB  - CWH41 encodes a novel type II integral membrane N-glycoprotein located in the
      endoplasmic reticulum. Disruption of the CWH41 gene leads to a K1 killer toxin
      resistant phenotype and a 50% reduction in the cell wall beta 1,6-glucan level.
      CWH41 also displays strong genetic interactions with KRE1 and KRE6, two genes
      known to be involved in the beta 1,6-glucan biosynthetic pathway. The cwh41 delta
      kre6 delta double mutant is nonviable; and the cwh41 delta kre1 delta double
      mutation results in strong synergistic defects, with a severely slow-growth
      phenotype, a 75% reduction in beta 1,6-glucan level, and the secretion of a cell
      wall glucomannoprotein, Cwp1p. These results provide strong genetic evidence
      indicating that Cwh41p plays a functional role, possibly as a new synthetic
      component, in the assembly of cell wall beta 1,6-glucan.

PMID- 8576052
TI  - Multicopy suppressors of prc mutant Escherichia coli include two HtrA (DegP)
      protease homologs (HhoAB), DksA, and a truncated R1pA.
AB  - We have isolated three multicopy suppressors of the conditional lethal phenotype
      of a prc (tsp) null strain of Escherichia coli. One of these suppressors included
      two novel putative protease genes in tandem that map to 3400 kb or 72.5
      centisomes on the chromosome. We propose the names hhoA and hhoB, for htrA
      homolog, to denote that these genes encode proteins that are 58 and 35%
      identical, respectively, to the HtrA (DegP) serine protease and 36% identical to
      each other. The HhoA and HhoB proteins are predicted to be 455 and 355 amino
      acids, respectively, in length. The mature HhoA protein is periplasmic in
      location, and amino-terminal sequencing shows that it arises following cleavage
      of a 27-amino-acid signal peptide. Searches of the protein and DNA databases
      reveal a rapidly growing family of homologous genes in a variety of other
      bacteria, including several which are required for virulence in their host.
      Deletion of the hhoAB genes shows that they are not required for viability at
      high temperatures like the homologous htrA but grow more slowly than wild-type
      strains. A second multicopy prc suppressor is the dksA (dnaK suppressor) gene,
      which is also a multicopy suppressor of defects in the heat shock genes dnaK,
      dnaJ, and grpE. The dksA gene was independently isolated as a multicopy
      suppressor of a mukB mutation, which is required for chromosomal partitioning. A
      third dosage-dependent prc suppressor includes a truncated rare lipoprotein A
      (rlpA) gene.

PMID- 8576054
TI  - Adherence, accumulation, and cell division of a natural adherent bacterial
      population.
AB  - Developing dental bacterial plaques formed in vivo on enamel surfaces were
      examined in specimens from 18 adult volunteers during the first day of plaque
      formation. An intraoral model placing enamel pieces onto teeth was used to study
      bacterial plaque populations developing naturally to various cell densities per
      square millimeter of surface area of the enamel (W. F. Liljemark, C. G.
      Bloomquist, C. L. Bandt, B. L. Philstrom, J. E. Hinrichs, and L. F. Wolff, Oral
      Microbiol. Immunol. 8:5-15, 1993). Radiolabeled nucleoside incorporation was used
      to measure DNA synthesis concurrent with the taking of standard viable cell
      counts of the plaque samples. Results showed that in vivo plaque formation began
      with the rapid adherence of bacteria until ca. 12 to 32% of the enamel's salivary
      pellicle was saturated (ca. 2.5 x 10(5) to 6.3 x 10(5) cells per mm2). The
      pioneer adherent species were predominantly those of the "sanguis streptococci."
      At the above-noted density, the bacteria present on the salivary pellicle
      incorporated low levels of radiolabeled nucleoside per viable cell. As bacterial
      numbers reached densities between 8.0 x 10(5) and 2.0 x 10(6) cells per mm2,
      there was a small increase in the incorporation of radiolabeled nucleosides per
      cell. At 2.5 x 10(6) to 4.0 x 10(6) cells per mm2 of enamel surface, there was a
      marked increase in the incorporation of radiolabeled nucleosides per cell which
      appeared to be cell-density dependent. The predominant species group in
      developing dental plaque films during density-dependent growth was the sanguis
      streptococci; however, most other species present showed similar patterns of
      increased DNA synthesis as the density noted above approached 2.5 x 10(6) to 4.0
      x 10(6) cells per mm2.

PMID- 8576055
TI  - Identification of a membrane protein involved in activation of the KinB pathway
      to sporulation in Bacillus subtilis.
AB  - The initiation of sporulation in Bacillus subtilis is dependent on the
      phosphorylation of the Spo0A transcription factor mediated by the phosphorelay
      and by two major kinases, KinA and KinB. Temporal expression of these kinases was
      analyzed, and an assessment of their respective contributions to the production
      of Spo0A-P was undertaken. The results show that KinB is expressed and activated
      prior to KinA; i.e., the two kinases are solicited sequentially in the
      sporulation process and are thought to be activated by different signaling
      pathways. A strategy was developed to isolate mutations specifically affecting
      the KinB pathway, using the newly improved mini-Tn10 delivery vector pIC333.
      Several mutants were obtained, one of which carried a transposon in a gene coding
      for a small integral membrane protein, named KbaA. Inactivation of the kbaA gene
      appeared to affect KinB activity but not transcription of kinB. A Spo+ suppressor
      (kinB45) of the kbaA null mutation was isolated in the promoter region of kinB.
      An eightfold increase of kinB expression levels over wild-type levels was
      observed in the kinB45 mutant. Thus, overexpression of the kinB-kapB operon was
      sufficient to overcome the sporulation defect caused by inactivation of kbaA in a
      KinA- strain. Transcription of kinB was found to be repressed by SinR, while the
      kinB45 mutant was no longer sensitive to SinR regulation. Implications of these
      observations on the transcriptional regulation of kinB and the role of KbaA in
      KinB activation are discussed.

PMID- 8576056
TI  - Metabolic effects of inhibitors of two enzymes of the branched-chain amino acid
      pathway in Salmonella typhimurium.
AB  - The metabolic effects of inhibitors of two enzymes in the pathway for
      biosynthesis of branched-chain amino acids were examined in Salmonella
      typhimurium mutant strain TV105, expressing a single isozyme of acetohydroxy acid
      synthase (AHAS), AHAS isozyme II. One inhibitor was the sulfonylurea herbicide
      sulfometuron methyl (SMM), which inhibits this isozyme and AHAS of other
      organisms, and the other was N-isopropyl oxalylhydroxamate (IpOHA), which
      inhibits ketol-acid reductoisomerase (KARI). The effects of the inhibitors on
      growth, levels of several enzymes of the pathway, and levels of intermediates of
      the pathway were measured. The intracellular concentration of the AHAS substrate
      2-ketobutyrate increased on addition of SMM, but a lack of correlation between
      increased ketobutyrate and growth inhibition suggests that the former is not the
      immediate cause of the latter. The levels of the keto acid precursor of valine,
      but not of the precursor of isoleucine, were drastically decreased by SMM, and
      valine, but not isoleucine, partially overcame SMM inhibition. This apparent
      stronger effect of SMM on the flux into the valine arm, as opposed to the
      isoleucine arm, of the branched-chain amino acid pathway is explained by the
      kinetics of the AHAS reaction, as well as by the different roles of pyruvate,
      ketobutyrate, and the valine precursor in metabolism. The organization of the
      pathway thus potentiates the inhibitory effect of SMM. IpOHA has strong initial
      effects at lower concentrations than does SMM and leads to increases both in the
      acetohydroxy acid substrates of KARI and, surprisingly, in ketobutyrate. Valine
      completely protected strain TV105 from IpOHA at the MIC. A number of explanations
      for this effect can be ruled out, so that some unknown arrangement of the enzymes
      involved must be suggested. IpOHA led to initial cessation of growth, with
      partial recovery after a time whose duration increased with the inhibitor
      concentration. The recovery is apparently due to induction of new KARI synthesis,
      as well as disappearance of IpOHA from the medium.

PMID- 8576057
TI  - Expression of the Bacillus subtilis sacB gene confers sucrose sensitivity on
      mycobacteria.
AB  - Expression in mycobacteria of the structural gene sacB, which encodes the
      Bacillus subtilis levansucrase, was investigated. sacB expression is lethal to
      Mycobacterium smegmatis and Mycobacterium bovis BCG in the presence of 10%
      sucrose. sacB could thus be used as a counterselectable marker in mycobacteria.

PMID- 8576058
TI  - Interactions of the CelS binding ligand with various receptor domains of the
      Clostridium thermocellum cellulosomal scaffolding protein, CipA.
AB  - The Clostridium thermocellum cellulosomal scaffolding protein, CipA, acts as an
      anchor on the cellulose surface for the various catalytic subunits of the
      cellulosome, a large extracellular cellulase complex. CipA contains nine repeated
      domains that serve as receptors for the cellulosomal catalytic subunits, each of
      which carries a conserved, duplicated ligand sequence (DS). Four representative
      CipA receptor domains with sequence dissimilarity were cloned and expressed in
      Escherichia coli. The interaction of these cloned receptor domains with the
      duplicated ligand sequence of CelS (expressed as a thioredoxin fusion protein,
      TRX-DSCelS), was studied by nondenaturing polyacrylamide gel electrophoresis. TRX
      DSCelS formed a stable complex with each of the four receptor domains, indicating
      that CelS, the most abundant cellulosomal catalytic subunit, binds nonselectively
      to all of the CipA receptors. Conversely, the duplicated sequence of CipA (in the
      form of TRX-DSCipA), which is homologous to that of CelS, did not bind to any of
      the receptors under the experimental conditions.

PMID- 8576059
TI  - Osmotic shock induction of capsule synthesis in Escherichia coli K-12.
AB  - The genes (cps) involved in the synthesis of the colanic acid capsular
      polysaccharide in Escherichia coli K-12 are transcriptionally regulated by
      numerous proteins. Two of these, RcsB and RcsC, share homology with two-component
      regulatory elements that respond to environmental stimuli. Osmotic shock by
      sucrose or NaCl transiently increased transcription of a cpsB::lacZ fusion. RcsC
      and RcsB were essential for osmotic induction of colanic acid synthesis. In
      contrast to observations in some other osmotically regulated systems, addition of
      glycine betaine enhanced the osmotic induction of cps::lacZ by both sucrose and
      NaCl but had no effect alone.

PMID- 8576060
TI  - VirE1 protein mediates export of the single-stranded DNA-binding protein VirE2
      from Agrobacterium tumefaciens into plant cells.
AB  - Agrobacterium tumefaciens transfers single-stranded DNAs (T strands) into plant
      cells. VirE1 and VirE2, which is a single-stranded DNA binding protein, are
      important for tumorigenesis. We show that T strands and VirE2 can enter plant
      cells independently and that export of VirE2, but not of T strands, depends on
      VirE1.

PMID- 8576062
TI  - Cloning and heterologous expression of the entire set of structural genes for
      nikkomycin synthesis from Streptomyces tendae Tu901 in Streptomyces lividans.
AB  - A genomic library from Streptomyces tendae raised in shuttle cosmid vector pKC505
      was screened with a previously isolated 8-kb DNA fragment containing the orfP1
      gene, which is involved in nikkomycin biosynthesis. The entire set of structural
      genes for nikkomycin synthesis was heterologously expressed in S. lividans TK23
      by introducing recombinant cosmids p24/32 and p9/43-2, carrying inserts of about
      31 and 27 kb, respectively, overlapping by 15 kb. S. lividans transformants
      synthesized nikkomycins X, Z, I, and J, which were identified by high-pressure
      liquid chromatography analyses of culture filtrates.

PMID- 8576061
TI  - Assembly-defective OmpC mutants of Escherichia coli K-12.
AB  - Novel ompC(Dex) alleles were utilized to isolate mutants defective in OmpC
      biogenesis. These ompC(Dex) alleles also conferred sensitivity to sodium dodecyl
      sulfate (SDS), which permitted the isolation of SDS-resistant and OmpC-specific
      phage-resistant mutants that remained Dex+. Many mutants acquired resistance
      against these lethal agents by lowering the OmpC level present in the outer
      membrane. In the majority of these mutants, a defect in the assembly (metastable
      to stable trimer formation) was responsible for lowering OmpC levels. The
      assembly defects in various mutant OmpC proteins were caused by single-amino-acid
      substitutions involving the G-39, G-42, G-223, G-224, Q-240, G-251, and G-282
      residues of the mature protein. This assembly defect was correctable by an
      assembly suppressor allele, asmA3. In addition, we investigated one novel OmpC
      mutant in which an assembly defect was caused by a disulfide bond formation
      between two nonnative cysteine residues. The assembly defect was fully corrected
      in a genetic background in which the cell's ability to form disulfide bonds was
      compromised. The assembly defect of the two-cysteine OmpC protein was also mended
      by asmA3, whose suppressive effect was not achieved by preventing disulfide bond
      formation in the mutant OmpC protein.

PMID- 8576063
TI  - The periplasmic TorT protein is required for trimethylamine N-oxide reductase
      gene induction in Escherichia coli.
AB  - Expression of the Escherichia coli torCAD operon, which encodes the
      trimethylamine N-oxide reductase system, is regulated by the presence of
      trimethylamine N-oxide through the action of the TorR response regulator. We have
      identified an additional gene, torT, located just downstream from the torR gene,
      which is necessary for torCAD structural operon expression. Insertion within the
      torT gene dramatically reduced the expression of a torA'-'lacZ fusion, while
      presence of the gene in trans restored the wild-type phenotype. Overproduction of
      TorR in a torT strain resulted in partial constitutive expression of the torA'
      'lacZ fusion, suggesting that TorR acts downstream from TorT. The torT gene codes
      for a 35.7-kDa periplasmic protein which presents some homology with the
      periplasmic ribose-binding protein of E. coli. We discuss the possible role of
      TorT as an inducer-binding protein involved in signal transduction of the tor
      regulatory pathway.

PMID- 8576064
TI  - Pyrroloquinoline quinone, a chemotactic attractant for Escherichia coli.
AB  - Escherichia coli is attracted by pyrroloquinoline quinone (PQQ), and chemotaxis
      toward glucose is enhanced by the presence of PQQ. A ptsI mutant showed no
      chemotactic response to either glucose or PQQ alone but did show a chemotactic
      response to a mixture of glucose and PQQ. A strain lacking the methylated
      chemotaxis receptor protein Tar showed no response to PQQ.

PMID- 8576066
TI  - Random and directed mutagenesis to elucidate the functional importance of helix
      II and F-989 in the C-terminal secretion signal of Escherichia coli hemolysin.
AB  - The HlyA secretion signal sequence of approximately 46 residues is predicted to
      contain helix I and an amphipathic helix II separated by a short loop including
      the conserved Phe residue, F-989. All nine substitutions of Phe-989 drastically
      reduce secretion of HlyA. Directed mutagenesis identified a functional hot spot,
      EISK, in helix II. However, genetic analysis did not provide strong support for a
      functional helix II; rather, the results emphasized that individual residues, for
      example, E-978 and F-989, are essential irrespective of a specific secondary
      structure.

PMID- 8576065
TI  - Analysis of the Erwinia chrysanthemi ferrichrysobactin receptor gene: resemblance
      to the Escherichia coli fepA-fes bidirectional promoter region and homology with
      hydroxamate receptors.
AB  - The fct cbsCEBA operon from the Erwinia chrysanthemi 3937 chrysobactin-dependent
      iron assimilation system codes for transport and biosynthetic functions. The
      sequence of the fct outer membrane receptor gene was determined. The fct promoter
      region displays a strong resemblance to the Escherichia coli bidirectional
      intercistronic region controlling the expression of the fepA-entD and fes-entF
      operons. An apparent Fur-binding site was shown to confer iron regulation on an
      fct::lac fusion expressed on a low-copy-number plasmid in a Fur-proficient E.
      coli strain. The fct gene consists of an open reading frame encoding a 735-amino
      acid polypeptide with a signal sequence of 38 residues. The Fct protein has 36%
      sequence homology with the E. coli ferrichrome receptor FhuA and the Yersinia
      enterocolitica ferrioxamine receptor FoxA. On the basis of secondary-structure
      predictions and these homologies, we propose a two-dimensional folding model for
      Fct.

PMID- 8576067
TI  - The glucose effect and regulation of alpha-amylase synthesis in the
      hyperthermophilic archaeon Sulfolobus solfataricus.
AB  - An alpha-amylase was purified from culture supernatants of Sulfolobus
      solfataricus 98/2 during growth on starch as the sole carbon and energy source.
      The enzyme is a homodimer with a subunit mass of 120 kDa. It catalyzes the
      hydrolysis of starch, dextrin, and alpha-cyclodextrin with similar efficiencies.
      Addition of exogenous glucose represses production of alpha-amylase,
      demonstrating that a classical glucose effect is operative in this organism.
      Synthesis of [35S]-alpha-amylase protein is also subject to the glucose effect.
      alpha-Amylase is constitutively produced at low levels but can be induced further
      by starch addition. The absolute levels of alpha-amylase detected in culture
      supernatants varied greatly with the type of sole carbon source used to support
      growth. Aspartate was identified as the most repressing sole carbon source for
      alpha-amylase production, while glutamate was the most derepressing. The pattern
      of regulation of alpha-amylase production seen in this organism indicates that a
      catabolite repression-like system is present in a member of the archaea.

PMID- 8576068
TI  - Genetic evidence for an activator required for induction of colicin-like
      bacteriocin 28b production in Serratia marcescens by DNA-damaging agents.
AB  - Bacteriocin 28b production is induced by mitomycin in wild-type Serratia
      marcescens 2170 but not in Escherichia coli harboring the bacteriocin 28b
      structural gene (bss). Studies with a bss-lacZ transcriptional fusion showed that
      mitomycin increased the level of bss gene transcription in S. marcescens but not
      in the E. coli background. A S. marcescens Tn5 insertion mutant was obtained (S.
      marcescens 2170 reg::Tn5) whose bacteriocin 28b production and bss gene
      transcription were not increased by mitomycin treatment. Cloning and DNA
      sequencing of the mutated region showed that the Tn5 insertion was flanked by an
      SOS box sequence and three genes that are probably cotranscribed (regA, regB, and
      regC). These three genes had homology to phage holins, phage lysozymes, and the
      Ogr transcriptional activator of P2 and related bacteriophages, respectively.
      Recombinant plasmid containing this wild-type DNA region complemented the
      reg::Tn5 regulatory mutant. A transcriptional fusion between a 157-bp DNA
      fragment, containing the apparent SOS box upstream of the regA gene, and the cat
      gene showed increased chloramphenicol acetyltransferase activity upon mitomycin
      treatment. Upstream of the bss gene, a sequence similar to the consensus sequence
      proposed to bind Ogr protein was found, but no sequence similar to an SOS box was
      detected. Our results suggest that transcriptional induction of bacteriocin 28b
      upon mitomycin treatment is mediated by the regC gene whose own transcription
      would be LexA dependent.

PMID- 8576069
TI  - Mutational analysis of the input domain of the VirA protein of Agrobacterium
      tumefaciens.
AB  - The transmembrane sensor protein VirA activates VirG in response to high levels
      of acetosyringone (AS). In order to respond to low levels of AS, VirA requires
      the periplasmic sugar-binding protein ChvE and monosaccharides released from
      plant wound sites. To better understand how VirA senses these inducers, the C58
      virA gene was randomly mutagenized, and 14 mutants defective in vir gene
      induction and containing mutations which mapped to the input domain of VirA were
      isolated. Six mutants had single missense mutatiions in three widely separated
      areas of the periplasmic domain. Eight mutants had mutations in or near an
      amphipathic helix, TM1, or TM2. Four of the mutations in the periplasmic domain,
      when introduced into the corresponding A6 virA sequence, caused a specific defect
      in the vir gene response to glucose. This suggests that most of the periplasmic
      domain is required for the interaction with, or response to, ChvE. Three of the
      mutations from outside the periplasmic domain, one from each transmembrane domain
      and one from the amphiphathic helix, were made in A6 virA. These mutants were
      defective in the vir gene response to AS. These mutations did not affect the
      stability or topology of VirA or prevent dimerization; therefore, they may
      interfere with detection of AS or transmission of the signals to the kinase
      domain. Characterization of C58 chvE mutants revealed that, unlike A6 VirA, C58
      VirA requires ChvE for activation of the vir genes.

PMID- 8576070
TI  - Modulation of luminescence operon expression by N-octanoyl-L-homoserine lactone
      in ainS mutants of Vibrio fischeri.
AB  - Population density-dependent expression of luminescence in Vibrio fischeri is
      controlled by the autoinducer N-3-oxohexanoyl-L-homoserine lactone (autoinducer 1
      [AI-1]), which via LuxR activates transcription of the lux operon (luxICDABEG,
      encoding the putative autoinducer synthase [LuxI] and the luminescence enzymes).
      We recently identified a novel V. fischeri locus, ainS, necessary for the
      synthesis of a second autoinducer, N-octanoyl-L-homoserine lactone (AI-2), which
      via LuxR can activate lux operon transcription in the absence of AI-1. To define
      the regulatory role of AI-2, a luxI ainS double mutant was constructed; in
      contrast to the parental strain and a luxI mutant, the luxI ainS mutant exhibited
      no induction of luminescence and produced no detectable luminescence autoinducer,
      demonstrating that V. fischeri makes no luminescence autoinducers other than
      those whose synthesis is directed by luxI and ainS. A mutant defective only in
      ainS exhibited accelerated luminescence induction compared with that of the
      parental strain, indicating that AI-2 functions in V. fischeri to delay
      luminescence induction. Consistent with that observation, the exogenous addition
      of AI-2 inhibited induction in a dose-dependent manner in V. fischeri and
      Escherichia coli carrying the lux genes. AI-2 did not mediate luxR negative
      autoregulation, alone or in the presence of AI-1, and inhibited luminescence
      induction in E. coli regardless of whether luxR was under the control of its
      native promoter or a foreign one. Increasing amounts of AI-1 overcame the
      inhibitory effect of AI-2, and equal activation of luminescence required 25- to
      45-fold-more AI-2 than AI-1. We conclude that AI-2 inhibits lux operon
      transcription. The data are consistent with a model in which AI-2 competitively
      inhibits the association of AI-1 with LuxR, forming a complex with LuxR which has
      a markedly lower lux operon-inducing specific activity than that of AI-1-LuxR. AI
      2 apparently functions in V. fischeri to suppress or delay induction at low and
      intermediate population densities.

PMID- 8576071
TI  - Suppression of a signaling defect during Myxococcus xanthus development.
AB  - The csgA gene encodes an extracellular protein that is essential for cell-cell
      communication (C-signaling) during fruiting body development of Myxococcus
      xanthus. Two transposon insertions in the socABC operon, soc-560 and socC559,
      restore development to csgA null mutants. Mixing soc-560 csgA cells or socC559
      csgA cells with csgA cells at a ratio of 1:1 stimulated the development of csgA
      cells, suggesting that soc mutations allow cells to produce the C-signal or a
      similar molecule via a csgA-independent mechanism. The socABC operon contains the
      following three genes: socA, a member of the short-chain alcohol dehydrogenase
      gene family; socB, a gene encoding a putative membrane anchoring protein; and
      socC, a negative autoregulator of socABC operon expression. Both suppressor
      mutations inactivate socC, leading to a 30- to 100-fold increase in socA
      transcription; socA expression in suppressor strains is at least 100-fold higher
      than csgA expression during all stages of development. The amino acid sequence of
      SocA has 28% identity and 51% similarity with that of CsgA. We suggest that CsgA
      suppression is due to overproduction of SocA, which can substitute for CsgA.
      These results raise the possibility that a cell surface dehydrogenase plays a
      role in C-signaling.

PMID- 8576074
TI  - Sequence-specific and hydrolytic scission of DNA and RNA by lanthanide complex
      oligoDNA hybrids.
AB  - Totally synthetic and sequence-specific nucleases and ribonucleases, which
      hydrolyze DNAs and RNAs selectively at target sites, have been prepared.
      Lanthanide ions, which efficiently hydrolyze the phosphodiester linkages in
      nucleic acids, are attached to the 5'-end of synthetic DNA oligomers (sequence
      recognizing sites) by use of an iminodiacetate ligand. Under physiological
      conditions, the hybrids selectively hydrolyze substrate DNA or RNA at the 3'-side
      of the sequence which is complementary with the DNA oligomers in the hybrids. The
      cerium(IV) ion is the most active as to DNA scission, whereas the europium(III),
      thulium(III), and lutetium(III) ions are the most effective for RNA scission. All
      the scissions proceed totally via hydrolysis of the phosphodiester linkages, in
      the same way as the scissions by natural nucleases and ribonucleases do. The
      artificial enzymes, which show far greater sequence-specificities than natural
      ones, exhibit high potential for application to molecular biology, biotechnology,
      and therapy.

PMID- 8576076
TI  - Crystallization and preliminary X-ray studies of isocitrate dehydrogenase from
      Thermus thermophilus HB8.
AB  - Isocitrate dehydrogenase from the thermophilic bacterium, Thermus thermophilus
      HB8, was crystallized by the vapor diffusion hanging drop method with
      polyethylene glycol 6000 as the precipitant. Pillar-like crystals of about 0.6 x
      0.6 x 0.3 mm3 were obtained. Analysis of a series of oscillation photographs
      indicated that the orthorhombic crystals belonged to the I222 or I2(1)2(1)2(1)
      space group with unit cell dimensions of a = 100.1 A, b = 150.4 A, and c = 87.4
      A. Intensity data were collected up to 2.5 A resolution.

PMID- 8576075
TI  - Biogenesis of novel quinone coenzymes.
AB  - Recently, two novel quinonoid coenzymes, 2,4,5-trihydroxyphenylalanine quinone
      (topa quinone; TPQ) and tryptophan tryptophylquinone (TTQ), were identified in
      copper-containing amine oxidase and methylamine dehydrogenase, respectively.
      Unlike the formerly known quinonoid coenzyme, pyrroloquinoline quinone (PQQ),
      which is non-covalently bound to several prokaryotic dehydrogenases and produced
      through its own biosynthetic pathway, each of TPQ and TTQ is bound covalently to
      the polypeptide chain as an integral amino acid residue and encoded by a codon
      for a normal (unmodified) amino acid in the gene. Thus, these coenzymes must be
      generated through post-translational modification of the precursor amino acid;
      for TPQ, oxidation of a specific tyrosine occurring in the consensus Asn-Tyr
      Asp/Glu sequence, and for TTQ, oxidation of a specific tryptophan and cross
      linking with another tryptophan separated by 50 residues in the same polypeptide
      chain. We recently demonstrated that, using the inactive precursor forms of
      bacterial copper amine oxidases, TPQ is generated through self-processing of the
      protein with the participation of the bound copper ions. On the other hand, the
      absence of a prosthetic metal ion in methylamine dehydrogenase as well as its
      existence in the periplasm renders TTQ biogenesis more complicated, likely
      requiring an external enzymatic system(s).

PMID- 8576072
TI  - Control of hemA expression in Rhodobacter sphaeroides 2.4.1: regulation through
      alterations in the cellular redox state.
AB  - Rhodobacter sphaeroides 2.4.1 has the ability to synthesize a variety of
      tetrapyrroles, reflecting the metabolic versatility of this organism and making
      it capable of aerobic, anaerobic, photosynthetic, and diazotrophic growth. The
      hemA and hemT genes encode isozymes that catalyze the formation of 5
      aminolevulinic acid, the first step in the biosynthesis of all tetrapyrroles
      present in R. sphaeroides 2.4.1. As part of our studies of the regulation and
      expression of these genes, we developed a genetic selection that uses transposon
      mutagenesis to identify loci affecting the aerobic expression of the hemA gene.
      In developing this selection, we found that sequences constituting an open
      reading frame immediately upstream of hemA positively affect hemA transcription.
      Using a transposon-based selection for increased hemA expression in the absence
      of the upstream open reading frame, we isolated three independent mutants. We
      have determined that the transposon insertions in these strains map to three
      different loci located on chromosome 1. One of the transposition sites mapped in
      the vicinity of the recently identified R. sphaeroides 2.4.1 homolog of the
      anaerobic regulatory gene fnr. By marker rescue and DNA sequence analysis, we
      found that the transposition site was located between the first two genes of the
      cco operon in R. sphaeroides 2.4.1, which encodes a cytochrome c terminal
      oxidase. Examination of the phenotype of the mutant strain revealed that, in
      addition to increased aerobic expression of hemA, the transposition event also
      conferred an oxygen-insensitive development of the photosynthetic membranes. We
      propose that the insertion of the transposon in cells grown in the presence of
      high oxygen levels has led to the generation of a cellular redox state resembling
      either reduced oxygen or anaerobiosis, thereby resulting in increased expression
      of hemA, as well as the accumulation of spectral complex formation. Several
      models are presented to explain these findings.

PMID- 8576073
TI  - The 18-kilodalton Chlamydia trachomatis histone H1-like protein (Hc1) contains a
      potential N-terminal dimerization site and a C-terminal nucleic acid-binding
      domain.
AB  - The Chlamydia trachomatis histone H1-like protein (Hc1) is a DNA-binding protein
      specific for the metabolically inactive chlamydial developmental form, the
      elementary body. Hc1 induces DNA condensation in Escherichia coli and is a strong
      inhibitor of transcription and translation. These effects may, in part, be due to
      Hc1-mediated alterations of DNA topology. To locate putative functional domains
      within Hc1, polypeptides Hc1(2-57) and Hc1(53-125), corresponding to the N- and C
      terminal parts of Hc1, respectively, were generated. By chemical cross-linking
      with ethylene glycol-bis (succinic acid N-hydroxysuccinimide ester), purified
      recombinant Hc1 was found to form dimers. The dimerization site was located in
      the N-terminal part of Hc1 (Hc1(2-57)). Moreover, circular dichroism measurements
      indicated an overall alpha-helical structure of this region. By using limited
      proteolysis, Southwestern blotting, and gel retardation assays, Hc1(53-125) was
      shown to contain a domain capable of binding both DNA and RNA. Under the same
      conditions, Hc1(2-57) had no nucleic acid-binding activity. Electron microscopy
      of Hc1-DNA and Hc1(53-125)-DNA complexes revealed differences suggesting that the
      N-terminal part of Hc1 may affect the DNA-binding properties of Hc1.

PMID- 8576077
TI  - Revised sequence of ribonuclease U2 in the substrate-binding region.

PMID- 8576078
TI  - Different localization of tau protein kinase I/glycogen synthase kinase-3 beta
      from glycogen synthase kinase-3 alpha in cerebellum mitochondria.
AB  - We examined the subcellular distribution of two glycogen synthase kinase-3 (GSK
      3) isoforms in rat cerebellum. Results from immunoelectron microscopy and
      subcellular fractionation revealed that one isoform, tau protein kinase I/GSK-3
      beta (TPKI/GSK-3 beta), was present in mitochondria, but GSK-3 alpha was not.
      Although the two GSK-3 isoforms seem to have similar properties, the difference
      of subcellular localization observed here suggests that TPKI/GSK-3 beta fulfills
      some specific function in mitochondria.

PMID- 8576079
TI  - Characterization of epitopes in native and unfolded cobrotoxin: evidence of an
      immunodominant C-terminal region related to the production of precipitating and
      non-precipitating antibodies against cobrotoxin.
AB  - Rabbits hyperimmunized with cobrotoxin from Taiwan cobra venom produced non
      precipitating as well as precipitating antibodies. Both antibody preparations
      exhibited higher affinity for native cobrotoxin than for reduced and S
      carboxymethylated (RCM) cobrotoxin. This indicated that the epitope structures in
      cobrotoxin are mostly conformation-dependent. In order to identify the
      conformational epitopes, native cobrotoxin was hydrolyzed with acid protease A,
      and 12 peptides were obtained on HPLC. Three peptide fragments, AP-10, AP-11, and
      AP-12, showed pronounced antigenicities toward precipitating as well as non
      precipitating antibodies. AP-10, AP-11, and AP-12 contained a common segment in
      the C-terminal region of cobrotoxin, residues 43 to 62, with intact disulfide
      linkages. Complete removal of the C-terminal antibodies from antisera and
      precipitating antibodies on a C-terminal segment-Sepharose affinity column
      resulted in the loss of their precipitability with cobrotoxin, whilst restoration
      of precipitability was observed on the addition of the C-terminal antibodies to
      the C-terminal antibody-depleted antisera and precipitating antibodies. Studies
      on the antigenic structures of RCM-cobrotoxin revealed that RCM-cobrotoxin
      contains an immunodominant epitope at positions 22-38. The N-terminal and C
      terminal regions of RCM-cobrotoxin encompass other epitopes which exhibit low
      reactivities toward anti-RCM-cobrotoxin antibodies. However, no precipitated
      antigen-antibody complexes were observed with the mixture of anti-RCM-cobrotoxin
      antibodies and RCM-cobrotoxin. These results suggest that the inherently
      different immunogenicities with different segments might affect the
      precipitabilities of the resulting antibodies, and that the notable
      immunogenecity of the C-terminal region is related to the production of
      precipitating and non-precipitating antibodies against cobrotoxin.

PMID- 8576080
TI  - The significance of membrane lipids in exocytosis: control of liposome-evoked
      amylase release from secretory granules isolated from the rat parotid gland.
AB  - We investigated the significance of the plasma membrane lipid composition in
      exocytosis in an in vitro interaction system using an intact secretory granular
      fraction (SG) isolated from the rat parotid gland. When various liposomes (as a
      model of plasma membranes) were added to this assay system, rapid and transient
      amylase release from the SG was evoked and increased by Ca2+ in a concentration
      dependent manner. The extent depended upon not only the amount of liposomes but
      also their lipid composition. The addition of 1,2-diacylglycerol and phosphatidic
      acid to egg yolk phosphatidylcholine-liposomes remarkably facilitated the
      release. On the other hand, that of various free fatty acids had different
      effects depending upon their molecular species. Furthermore, a fluorescence de
      quenching study demonstrated that membrane fusion actually occurred in this
      interaction system, and appeared to correlate with the amylase release. These
      results suggest that the transient alteration of the membrane lipid composition
      upon cell activation is a modulator of the exocytotic membrane interaction.

PMID- 8576082
TI  - Secondary structure of holo- and apo-aminoacylase from prediction, circular
      dichroism, and FT-Raman spectroscopy.
AB  - The secondary structures of native (Holo-) and Zn(2+)-free (Apo-) aminoacylase
      were examined by circular dichroism (CD) and Fourier transform Raman (FT-Raman)
      spectroscopic techniques and prediction methods. Quantitative analysis of the
      conformationally sensitive amide I band indicates that Holo- and Apo-enzyme
      contain 19.3 and 17.2% helical structure, respectively. Far-UV CD spectra of Holo
      and Apo-enzyme show that they contain 20.1 and 17.6% alpha-helix, respectively.
      Secondary structure prediction of aminoacylase indicates that it contains
      approximately 20.9% alpha-helical structure including 10 alpha-helix segments.
      The results show that after removal of Zn2+ in aminoacylase, the extent of
      ordered structure was decreased markedly. The conformation at or near the active
      site of aminoacylase may contain more ordered structure and the presence of Zn2+
      may help to maintain the catalytically active conformation at the active site.

PMID- 8576081
TI  - Receptor-mediated interaction of the low-density lipoprotein complex with dextran
      sulfate: potential as a multi-biological coupler.
AB  - We have investigated the receptor-mediated binding and uptake of low-density
      lipoprotein (LDL) and its insoluble complex with dextran sulfate to determine the
      contribution of positively charged sites in LDL to receptor-mediated
      interactions. Rabbit plasma LDL derivatized with FITC retained its sedimentation
      ability with dextran sulfate, as well as intact LDL, and binding of fluorescent
      LDL and its complex to liver cells was assayed by flow cytometry. Flow cytometry
      revealed that the binding of complex LDL with dextran sulfate, as well as that of
      pure LDL, increased on rat liver parenchymal cells treated with estrogen, which
      enhanced the expression of LDL receptors, and decreased on Hep G2 and Chang Liver
      cells treated with a monoclonal antibody against LDL receptors. The binding of
      pure LDL and complex LDL to hepatocytes was depressed by pretreatment with
      unlabeled LDL in a similar manner, but not with asialoglycoprotein, a ligand of
      asialoglycoprotein receptors on liver cells. Furthermore, we carried out a stable
      primary culture of rat hepatocytes, and then pure LDL and complex LDL were
      applied to the cultured hepatocytes. Hepatic-differentiated functions such as
      albumin and bile acid secretion decreased on the uptake of pure LDL and complex
      LDL in a similar manner. Consequently, comparative studies using pure LDL and
      complex LDL allowed us to determine that the complex formation with dextran
      sulfate had no influence on the receptor-mediated binding or uptake of LDL, and
      that LDL possessed binding domains for LDL receptors and sulfonic carbohydrates,
      containing positively charged amino acids.

PMID- 8576083
TI  - Effects of replacement of Lys25 with Gln on the conformation of ribonuclease T1:
      sequence-specific 1H NMR resonance assignments of Gln25 ribonuclease T1 by two
      dimensional NMR spectroscopy.
AB  - Two isozymes of ribonuclease (RNase) T1 exist in nature, i.e. Gln25 RNase T1 and
      Lys25 RNase T1. Gln25 RNase T1 is less stable than Lys25 RNase T1, although the
      enzymatic activity is not distinguishable between these two isozymes. To
      elucidate the effects of the replacement of Lys25 with Gln on the conformation
      and microenvironments of RNase T1 in detail, two-dimensional NMR spectra were
      measured, sequence-specific 1H NMR resonance assignments of Gln25 RNase T1 were
      performed, and then the determined parameters and microenvironments of Gln25
      RNase T1 were compared with those of Lys25 isozyme [Hoffmann, E. and Ruterjans,
      H. (1988) Eur. J. Biochem. 177, 539-560]. The main chain protons were assigned
      for 101 out of the total of 104 amino acid residues. Secondary structure elements
      were identified from analysis of characteristic NOE patterns, interstrand NOE
      connectivities, and hydrogen-deuterium exchange rates of main chain amide
      protons. The results indicated that Gln25 RNase T1 contains a single alpha-helix
      and seven beta-strands. The secondary structure of Gln25 RNase T1 is, thus,
      essentially the same as that of Lys25 RNase T1. On the other hand, comparison of
      the conformation-dependent shifts of Gln25 RNase T1 with these of Lys25 RNase T1
      showed that the replacement of Lys25 with Gln has significant effects on the C
      terminal part of the alpha-helix region and the base-binding site. These results
      may indicate that the base-binding site is relatively flexible in the RNase T1
      molecule. Among the residues of the C-terminal part of the alpha-helix region,
      the protons of Asp29 were most affected in terms of their chemical shifts, which
      may indicate that the side chain carboxylate anion of Asp29 is the counterpart of
      the electrostatic interaction of Lys25 in Lys25 RNase T1. The Gln25 of Gln25
      RNase T1 may have little or no interaction with Asp29, and this may be the reason
      why Gln25 RNase T1 is less stable than the Lys25 isozyme.

PMID- 8576084
TI  - Structure of the mouse basigin gene, a unique member of the immunoglobulin
      superfamily.
AB  - Basigin is a membrane glycoprotein belonging to the immunoglobulin superfamily.
      The mouse basigin gene was isolated from a genomic DNA library of the BALB/c
      mouse, and the structure of the gene and its flanking region (11.8 kb) was
      completely determined. The mouse basigin gene consists of seven exons and six
      introns spanning 7.5 kb. The distance between the first and second exons is 5.1
      kb. The first immunoglobulin-like domain of the basigin molecule is encoded by
      the second and third exons, and the second immunoglobulin-like domain by the
      fourth and fifth exons. The fifth exon encodes not only the C proximal portion of
      the second immunoglobulin-like domain, but also the transmembrane domain and a
      small portion of the cytoplasmic domain. Thus, the organization of the basigin
      gene is unique. The 5' upstream sequence of the basigin gene contains no TATA box
      or CAAT box, but has a CpG-rich island. The BALB/c genomic sequence of all seven
      exons is consistent with the cDNA sequences of the 129/SV and Swiss mice except
      several minor substitutions in the 3'-terminal sequence of the 3'-noncoding
      region. No protein polymorphism has so far been found in basigin of different
      mouse strains.

PMID- 8576085
TI  - Isolation and characterization of the promoter region of the rat DNA
      topoisomerase II alpha gene.
AB  - A genomic DNA clone containing the 5'-end of the rat topo II alpha gene was
      isolated and the intron/exon structure of a 4.0 kb region encompassing the
      translation initiation site was determined. Multiple transcription initiation
      sites were found at positions -128, -110, and -100 bp upstream of the ATG codon.
      A minimal promoter region extending from -192 to the translation initiation codon
      was identified on transient expression analysis. This region lacks a TATA motif,
      is moderately GC-rich and contains a high number of CpG dinucleotides, which is
      characteristic of a housekeeping gene promoter. The fragment extending to
      position -242 exhibited maximal promoter activity. Putative regulatory elements
      were delineated within and immediately upstream of the minimal promoter region.
      On gel retardation and DNase I footprint analyses, two regions, between positions
      -195 to -159 which interact with protein factor(s) were identified. The minimal
      promoter region of the rat topo II alpha gene showed high sequence homology with
      that of human topo II alpha. In a 250 bp region upstream of the translation
      initiation site, the sequence identity was about 70%. The basic structure of the
      regulatory region of the rat topo II alpha gene was found to be similar to that
      of the human counterpart.

PMID- 8576086
TI  - Regulation of BPAG2 (180 kDa) gene expression in spontaneously transformed murine
      keratinocytes: tissue distribution, modulation during cell adhesion, and up
      regulation by ascorbic acid.
AB  - Messenger RNA for BPAG2, a hemidesmosomal type XVII collagen, was detected
      specifically in cultured keratinocytes, not in melanocytes or dermal fibroblasts,
      and was localized preferentially in the skin and cornea, not in aorta, lung,
      kidney, or liver. Modulation of BPAG2 mRNA expression during keratinocyte
      adhesion and growth in culture was studied. BPAG2 mRNA level in the spreading
      phase was greater than that in cell attaching and proliferating phases. Ascorbic
      acid stimulated the BPAG2 mRNA level to 2 times the control in a dose- and
      exposure time-dependent manner. These results suggest that BPAG2 is expressed at
      a maximum level in the cell spreading phase and is up-regulated by ascorbic acid.

PMID- 8576087
TI  - The primary structure of pepstatin-insensitive carboxyl proteinase produced by
      Pseudomonas sp. No. 101.
AB  - A unique carboxyl proteinase [EC 3.4.23.33] from Pseudomonas sp. No. 101 is the
      first example of a prokaryotic enzyme which is insensitive to the classical
      inhibitor, pepstatin. The primary structure of the proteinase was determined by
      conventional methods. Pseudomonas carboxyl proteinase consists of 370 amino acid
      residues with one disulfide bond. This enzyme has no homologous sequence with any
      other known carboxyl proteinase, including carboxyl proteinase B from Scytalidium
      lignicolum, which is a pepstatin-insensitive carboxyl proteinase. In addition,
      Pseudomonas carboxyl proteinase lacks the Asp*-Thr-Gly, Glu*-Thr-Gly, and Asp*
      Thr-Ser-Gly (*indicates the catalytic residue) sequences which are known as the
      motif sequences around a pair of catalytic residues in carboxyl proteinases
      reported so far. The results strongly indicate that Pseudomonas carboxyl
      proteinase is a new type of carboxyl proteinase.

PMID- 8576088
TI  - Ligand-induced changes in the conformation of 3-isopropylmalate dehydrogenase
      from Thermus thermophilus.
AB  - The structures of 3-isopropylmalate dehydrogenase (IPMDH) from Thermus
      thermophilus in complexes with its substrate, cofactor, and a cofactor analog
      were investigated by X-ray diffraction in a crystalline state and by small-angle
      X-ray scattering (SAXS) in solution. The structures at 2.8 A resolution of the
      complexes with the substrate, 3-isopropylmalate (IPM), and with an analog of NAD,
      ADP-ribose, were both very close to the structure of the free enzyme, which
      adopts an open conformation. However, the binding of a ligand induced a small
      conformational change near the binding site. This result contrasts with results
      for NADP(+)-bound and isocitrate-bound isocitrate dehydrogenase (ICDH) from
      Escherichia coli, which adopts a closed conformation. The SAXS analysis in
      solution clearly showed that IPMDH without a ligand adopts two distinct
      intermediate conformations, between the open and closed states, upon binding of
      NADH and IPM respectively, and adopts a fully closed conformation when in a
      ternary complex with NADH and IPM together.

PMID- 8576089
TI  - Avidin fusion protein as a tool to generate a stable translocation intermediate
      spanning the mitochondrial membranes.
AB  - We have designed a fusion gene encoding a chimeric mitochondrial precursor
      protein (avidin fusion protein) that consists of the mitochondrial presequence
      followed by mouse dihydrofolate reductase, a spacer segment, and streptavidin.
      The avidin fusion protein synthesized in vitro formed a tetramer at the avidin
      moiety on incubation with biotin during or after the translation reaction. The
      avidin fusion protein purified from the Escherichia coli overexpresser cells also
      formed the tetramer on dilution from 6M urea into buffer containing biotin. In in
      vitro import experiments with isolated yeast mitochondria, the tetramer of the
      avidin fusion protein became stuck across both mitochondrial membranes, with its
      N-terminal dihydrofolate reductase moiety in the matrix and its C-terminal avidin
      moiety exposed on the mitochondrial surface. Accumulation of the translocation
      intermediate of the fusion protein inhibited the import of a mitochondrial
      precursor protein, and allowed us to estimate the number of mitochondrial import
      sites.

PMID- 8576092
TI  - Complete covalent structure of porcine liver acylamino acid-releasing enzyme and
      identification of its active site serine residue.
AB  - The complete covalent structure of porcine liver acylamino acid-releasing enzyme
      (AARE) [EC3.4.19.1], which catalyzes the hydrolysis of an N-terminally acylated
      peptide to release an N-acylamino acid, has been established. On basis of the
      amino acid sequence deduced from the cDNA sequence of porcine liver AARE [Mitta,
      M. et al. (1989) J. Biochem. 106, 548-555], sequence determination has been
      achieved by automated Edman degradation of peptides generated by chemical or
      enzymatic cleavages of the reduced and S-carboxymethylated protein. Ion-spray
      mass spectrometry was also successfully used to confirm the amino acid sequences
      of the peptides determined above and to elucidate both the N-terminal blocking
      group and the status of half-cystine residues of this protein. The protein
      consists of 732 amino acid residues, and the N-terminal methionine residue is
      blocked by an acetyl group. All of 18 half-cystine residues of this protein were
      proved to exist as cysteine residues. A serine residue reactive with diisopropyl
      fluorophosphate (DFP) was also identified as Ser587 by preparation of the AARE
      labeled with tritiated DFP followed by isolation and sequence analysis of a
      radioactive peptide obtained from its endoproteinase Asp-N digest.

PMID- 8576090
TI  - Effects of anion transport inhibitors on hemolysis of human erythrocytes under
      hydrostatic pressure.
AB  - Effects of anion transport inhibitors on hemolysis of human erythrocytes at 200
      mPa were examined. The degree of hemolysis was decreased by treating intact cells
      with 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS), 4,4'-dinitrostilbene
      2,2'-disulfonate and pyridoxal 5'-phosphate (PLP) had little effect on the
      hemolysis. In contrast, the degree of hypotonic hemolysis increased upon
      treatment with anion transport, inhibitors. From the relationship between the
      hemolysis at 200 mPa and anion transport, it was found that high-pressure-induced
      hemolysis was suppressed by the covalent binding of anion transport inhibitors to
      band 3. This idea was supported by the finding that the hemolysis at 200 mPa of
      trypsin-treated erythrocytes was suppressed by DIDS. Furthermore, the spectrin
      content in vesicles which are released from erythrocyte ghost by dimyristoyl
      phosphatidylcholine decreased upon DIDS labeling of band 3, but did not change
      upon PLP labeling. These results suggest that the interaction of the cytoplasmic
      domain of band 3 with spectrin, perhaps via ankyrin, is tightened by the covalent
      binding of bulky ligands to the exofacial domain of band 3.

PMID- 8576091
TI  - Distribution and characterization of immunoreactive adrenomedullin in porcine
      tissue, and isolation of adrenomedullin [26-52] and adrenomedullin [34-52] from
      porcine duodenum.
AB  - Using a sensitive radioimmunoassay which recognizes the carboxy-terminal region
      of porcine adrenomedullin, the distribution of immunoreactive adrenomedullin was
      widely distributed in porcine tissue, and its concentration was highest in
      adrenal medulla (126 +/- 32 fmol/mg wet tissue; mean +/- SD). Relatively high
      concentrations of immunoreactive adrenomedullin were found in the right atrium,
      lung, duodenum, and pituitary gland. The molecular form of immunoreactive
      adrenomedullin in all porcine tissues was found to be almost wholly porcine
      adrenomedullin itself by analysis with reverse-phase high-performance liquid
      chromatography coupled with radioimmunoassay. Minor molecular forms of
      immunoreactive adrenomedullin were found in the porcine duodenum. These were
      isolated and identified as adrenomedullin [26-52] and adrenomedullin [34-52].

PMID- 8576093
TI  - Temporally distinctive changes of alternative splicing patterns during myogenic
      differentiation of C2C12 cells.
AB  - It is well known that skeletal muscle differentiation is accompanied by the
      appearance of many muscle-specific components and that some of these components
      are generated through muscle-specific alternative splicing. It is not clear,
      however, in what manner, including timing, the system that regulates the muscle
      specific splicing reactions is constructed during the process of myogenic
      differentiation. We simultaneously examined the changes in several splicing
      patterns for the neural cell adhesion molecule (NCAM), beta-tropomyosin, and M
      type pyruvate kinase genes during myogenic differentiation of cultured myoblasts
      using the reverse transcription-polymerase chain reaction method. The NCAM
      glycosylphosphatidylinositol anchor form increased in preference to the
      transmembrane form immediately after the induction of differentiation, while the
      selection of NCAM MSD1 (muscle-specific domain 1) exons started and abruptly
      increased at about the time when cell-fusion appeared. M2-type pyruvate kinase
      was gradually substituted for the M1-type molecule. Skeletal muscle-type beta
      tropomyosin was predominantly selected even in myoblasts in the growth medium. As
      a result, each transcript of these genes independently showed a temporally
      distinctive pattern of change in isoform selecting during the myogenic
      differentiation of C2C12 cells. These observations suggest that some independent
      regulation of alternative splicing reactions should occur during myogenic
      differentiation.

PMID- 8576094
TI  - Purification of low-molecular-weight GTP-binding proteins structurally related to
      MTG33, a mitochondrial GTP-binding protein of Ehrlich ascites tumor cells.
AB  - We purified a mitochondrial GTP-binding protein, MTG33, from a particulate
      fraction of Ehrlich ascites tumor cells [Takeda, S., Sagara, Y., Kita, K.,
      Natori, S., and Sekimizu, K. (1993) J. Biochem. 114, 684-690]. In the present
      work, three GTP-binding proteins, p23A, p23B, and p26, were purified from the
      same material. The Kd values of p23A, p23B, and p26 for GTP were 19, 6.8, and 4.0
      nM, respectively. Binding of [alpha-32P]GTP to these proteins was inhibited by
      GTP and GDP, but not appreciably by other nucleotides such as ATP, CTP, UTP, and
      GMP. p23A, p23B, and p26 hydrolyzed GTP to GDP as well as MTG33 did. Peptide
      mapping analyses revealed that these GTP-binding proteins share common primary
      structures with MTG33. The defined properties of the three proteins suggest
      structural and functional relations to MTG33, which is localized in mitochondria.

PMID- 8576095
TI  - Purification and reaction mechanism of arylsulfate sulfotransferase from
      Haemophilus K-12, a mouse intestinal bacterium.
AB  - A novel type of sulfotransferase, arylsulfate sulfotransferase [EC 2.8.2.22], was
      purified to homogeneity from Haemophilus K-12, a mouse intestinal bacterium. The
      purified enzyme (M(r) 290,000) is composed of four subunits (M(r) 70,000). The
      best donor substrate was 4-methylumbelliferyl sulfate, followed by beta-naphthyl
      sulfate, p-nitrophenyl sulfate (PNS), and alpha-naphthyl sulfate. The best
      acceptor substrate was alpha-naphthol, followed by phenol and resorcinol. The
      apparent Km for PNS using phenol as an acceptor and that for phenol and
      resorcinol. The apparent Km for PNS using phenol as an acceptor and that for
      phenol using PNS as a donor substrate were determined to be 0.095 and 0.71 mM,
      respectively. One of the reaction products, p-nitrophenol inhibited the enzyme
      noncompetitively with respect to PNS, but competitively with respect to alpha
      naphthol. The Ki values of PNP for PNS and alpha-naphthol were 0.89 and 0.12 mM,
      respectively. The other reaction product, alpha-naphthyl sulfate, inhibited the
      enzyme competitively with respect to PNS, but non-competitively with respect to
      alpha-naphthol. The Ki values of alpha-naphthyl sulfate for PNS and for alpha
      naphthol were 2.72 and 1.7 mM. These results suggest that the sulfate transfer
      reaction proceeds according to a ping pong bi bi mechanism.

PMID- 8576096
TI  - Transfection of human melanoma cells with type I interleukin-1 (IL-1) receptor
      cDNA rendered them IL-1-responsive and revealed the importance of ODC activity
      down-regulation in IL-1-induced growth inhibition.
AB  - A human type I IL-1 receptor expression plasmid has been constructed and used to
      transfect human melanoma cells (A375-5), which have been shown to be unresponsive
      to the antiproliferative effect of IL-1. Five stable transfectant cell lines have
      been established, of which three are sensitive and the other two resistant to the
      anti-proliferative effect of IL-1. All the transfectant cell lines, but not
      progenitor A375-5 cells, expressed functional type I IL-1 receptors and could
      produce IL-6 in response to IL-1, suggesting that the unresponsiveness of A375-5
      melanoma cells is exactly due to an IL-1 receptor deficiency. The three IL-1
      sensitive stable transfectant cell lines expressed much more type I IL-1 receptor
      than the IL-1-sensitive A375-6 cells, thus they are expected to be useful for
      investigating the signal transduction pathway of IL-1-induced growth inhibition
      in melanoma cells. The two resistant cell lines produced comparable amounts of IL
      6 in response to IL-1, as sensitive cell lines did, indicating that IL-6
      induction does not play a major role in IL-1-induced growth inhibition in these
      melanoma cells. The possibility of an IL-6 receptor and/or IL-6 receptor
      signaling deficiency was ruled out as the IL-1-sensitive and -resistant
      transfectants responded similarly to a high dose of exogenous human recombinant
      IL-6. Examination of the ornithine decarboxylase (ODC) activity of recombinant
      human IL-1 alpha treated cells showed that all the sensitive but none of the
      resistant cell lines could down-regulate their ODC activity. These results
      suggest that IL-1-induced ODC activity down-regulation is an important step in
      the signal transduction pathway of IL-1-induced growth inhibition of melanoma
      cells.

PMID- 8576097
TI  - Purification and properties of 3-hydroxyacyl coenzyme A dehydrogenase-binding
      protein from rat liver mitochondria.
AB  - Mitochondria isolated from rat liver were freeze-thawed and washed with 0.1 M
      potassium phosphate, pH 7.4. Most of the 3-hydroxyacyl coenzyme A (CoA)
      dehydrogenase activities were removed and this mitochondrial membrane fraction
      could bind exogenous 3-hydroxyacyl-CoA dehydrogenase. 3-Hydroxyacyl-CoA
      dehydrogenase-binding protein was extracted from the washed membrane fraction
      with a buffer containing 2% Triton X-100 and 2% sodium taurodeoxycholate. The
      binding protein was purified by Ultrogel AcA 34 gel chromatography, calcium
      phosphate gel-cellulose chromatography and 3-hydroxyacyl-CoA dehydrogenase
      affinity chromatography. The molecular mass of the purified binding protein was
      estimated to be 140 kDa by gel filtration and its subunit molecular mass was
      determined as 60 kDa by SDS-PAGE suggesting that the protein is a homodimer. The
      binding protein and 3-hydroxyacyl-CoA dehydrogenase formed a complex at low ionic
      strength and the stoichiometry revealed that 1 mol of the binding protein bound 2
      mol of 3-hydroxyacyl-CoA dehydrogenase. Purified 3-hydroxyacyl-CoA dehydrogenase
      binding protein interacted with 3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl
      CoA thiolase but did not bind other mitochondrial beta-oxidation enzymes. The pH
      optimum of the binding activity was from pH 6 to 7 and the binding activity was
      diminished by increasing the concentration of salt in the medium.

PMID- 8576098
TI  - Separation of protein factors that correct the defects in the seven
      complementation groups of xeroderma pigmentosum cells.
AB  - We fractionated HeLa cell extracts by gel filtration and then micro-injected them
      into cells derived from the seven complementation groups (A-G) of xeroderma
      pigmentosum (XP). Distinct fractions that corrected the unscheduled DNA synthesis
      (UDS) of the complementation group XP cells were identified. The apparent
      molecular weights corresponding to complementation groups A, B, C, D, E, F, and G
      were estimated to be 80, 600, 600, 240, 100, 240, and 280 kDa, respectively.
      These factors were stable in the respective cell lines, the shortest half life
      being 16 h for the XP-A and XP-G complementing factors. The fraction (80 kDa)
      that corrected the UDS in XP-A cells also complemented the defect of the XP-A
      cell extract in the incision of DNA containing a pyrimidine dimer in a cell-free
      system. The separated fractions will be useful for understanding the molecular
      nature of these factors and for assigning complementation groups of cells derived
      from suspected XP patients.

PMID- 8576099
TI  - Vl-linker-Vh orientation-dependent expression of single chain Fv-containing an
      engineered disulfide-stabilized bond in the framework regions.
AB  - Single chain Fv fragments (scFv) derived from an antibody, MAb 174H.64 (Tru
      ScintRSQ kit, Biomira), were constructed in both orientations, i.e. Vh-linker-Vl
      and Vl-linker-Vh, but only the latter form could be expressed and secreted in the
      recombinant Pichia pastoris system. The secreted scFv protein showed specific
      anti-idiotype binding activity. Additionally, the molecular graphic modeling has
      been used to identify a possible site for the introduction of an interchain
      disulfide bond in the framework region of Fv. These Cys-modifications of the
      sites were done using a method of PCR-mediated mutagenesis. The engineered
      protein (disulfide-stabilized Fv: dsFv) was expressed and tested for its binding
      activity. It was found that dsFv was as active as the corresponding scFv and more
      stable as determined by competitive radioimmunoassay.

PMID- 8576100
TI  - Permeability change of liposomal membrane induced by interleukin-1 alpha.
AB  - Interleukin-1 (IL-1) is produced and released by various cells, including
      activated macrophages, and plays important roles in inflammation as well as
      immune responses. Since the precursor of IL-1 has no signal peptide, the
      mechanism of IL-1 release has been an enigma. To investigate the possibility of
      direct interaction of IL-1 with the lipid bilayer, the interleukin-1 alpha (IL-1
      alpha)- or beta (IL-1 beta)-induced permeability change of the liposomal membrane
      was determined. IL-1 alpha, but not IL-1 beta, caused an increase in the
      permeability of liposomes composed of phosphatidylserine (PS), at neutral and
      acidic pHs, as demonstrated by measuring the efflux of calcein. On the other
      hand, liposomes composed of phosphatidylcholine (PC) showed no increase in
      permeability when incubated with IL-1 alpha, suggesting the importance of acidic
      phospholipids in the interaction of IL-1 alpha with the membrane. Furthermore,
      permeability of liposomal membrane was markedly increased by IL-1 alpha in the
      presence of 1 microM calcium ions, although a permeability change was observed
      even in the absence of calcium ions. IL-1 alpha also induced the efflux of
      fluorescent dextran (average M(r) of 39,600), raising the possibility of
      translocation of IL-1 alpha through the cell membrane.

PMID- 8576101
TI  - Cloning of an alternative form of plakoglobin (gamma-catenin) lacking the fourth
      armadillo repeat.
AB  - Plakoglobin is a member of a protein family with a repeating amino acid motif
      called the armadillo repeat, and is a cytoplasmic protein found in both adherens
      junctions and desmosomes. Little is known about its function, but it has been
      shown to form distinct complexes with cadherins or desmosomal cadherins. Also,
      plakoglobin has been shown to form a complex with APC, a tumor suppressor gene
      product. We have isolated a cDNA clone encoding plakoglobin by means of the
      polymerase chain reaction (PCR) from a human transitional carcinoma cell line.
      The cDNA has the same nucleotide sequence as the previously published one [Franke
      et al. (1989) Proc. Natl. Acad. Sci. USA 86, 4027-4031], except that it has a
      deletion of 120 bp. The deleted sequence encodes the fourth armadillo repeat.
      Southern blot analysis of genomic DNA revealed that there is a single copy of the
      plakoglobin gene per haploid genome. Cloning and sequencing of a genomic DNA
      fragment containing the 120-bp deletion and the surrounding sequences revealed
      that these sequences are encoded by a single exon sequence. PCR amplification of
      the genomic DNA fragment of the corresponding region excluded the possible
      presence of the 120-bp deletion in the gene. Therefore the variant form is most
      likely derived through alternative splicing of precursor RNA transcripts in an
      exon sequence.

PMID- 8576102
TI  - Template-dependent polypeptide synthesis in a factor- and energy-free translation
      system promoted by pyridine.
AB  - We demonstrate here that a high concentration (40-70%) of pyridine, an aromatic
      tertiary amine catalyst, is able to promote translation on ribosomes without the
      presence of soluble protein factors or chemical energy sources. Compared with
      Monro's fragment reaction [Methods Enzymol. 20, 472-481 (1971)] which reflects
      only the peptidyltransferase step, this novel translation system can produce
      polypeptides with chain lengths of at least several tens of residues depending on
      the template RNA. In the presence of 60% pyridine, poly(U) and poly(UC) promoted
      incorporation of the respective amino acids, phenylalanine and serine-leucine,
      twofold, whereas poly(A) promoted the incorporation of lysine by only 25%. The
      degrees of polymerization of phenylalanine and lysine were up to the decamer and
      around 40mer, respectively. In poly(UC)-dependent oligo(serine-leucine)
      synthesis, oligopeptides with a serine and leucine alternate sequence were the
      main products. This novel pyridine system evidently differs from the non
      enzymatic translation system reported by Gavrilova and Spirin [FEBS Lett. 17, 324
      326 (1971)]; the former system displays partial resistance toward
      deproteinization reagents such as SDS and proteinase K, whereas the latter system
      is completely sensitive.

PMID- 8576103
TI  - Factor- and energy-free peptide synthesis promoted by aromatic tertiary amines
      including nucleic acid-related compounds.
AB  - We have already reported a novel, in vitro translation system, promoted by
      pyridine instead of the usual protein factors and energy sources, which consists
      of only salt-washed ribosomes from Escherichia coli, aminoacyl-tRNA, a template
      RNA, Na+ and Mg2+ cations, and 40-60% pyridine [Nitta et al. (1994) J. Biochem.
      115, 803-807 and the accompanying paper]. Here we show that in this system,
      pyridine can be replaced not only by pyridine derivatives but also by nucleobases
      or nucleosides, demonstrating that any compound harboring an aromatic tertiary
      amine within the molecule possesses such promoting activity. These compounds may
      serve to assist the peptide bond formation catalyzed by peptidyltransferase
      within ribosomes. The finding that nucleobases and nucleosides can play such a
      role in this reaction implies the possibility that these compounds were directly
      involved in the premordial translation system.

PMID- 8576105
TI  - Structural organization of transcription termination factor Rho.

PMID- 8576104
TI  - Substrate specificity of rabbit liver metalloendopeptidase and its new
      fluorogenic peptide substrates.
AB  - A metalloendopeptidase (MEP) isolated from rabbit liver microsomes with substrate
      specificity for peptides containing Arg at the P1 and P4 positions has recently
      proved to be identical to soluble angiotensin-binding protein present in the
      cytosol. Here we describe the peptide-degrading specificity of MEP, determined
      using various bioactive peptides and novel fluorogenic substrates for the enzyme.
      MEP degraded oligopeptides, including bradykinin, alpha-neoendorphin, bovine
      adrenal medulla dodecapeptide, substance P, bombesin, neurotensin, and alpha
      endorphin, but not polypeptides such as reduced lysozyme and histone H4, hence,
      MEP probably belongs to the family of endo-oligopeptidases. It cleaved most
      preferentially at the -Phe-Ser- bond of bradykinin (kcat/Km = 2.8 x 10(4) M-1.S
      1) but did not cleave high molecular weight and low molecular weight kininogens,
      the precursors of bradykinin. MEP did not cleave angiotensin I, dynorphin A 1-13,
      somatostatin, and luteinizing hormone-releasing hormone, some of which are good
      substrates for metalloendopeptidase-24.15, metalloendopeptidase-24.16, N-arginine
      dibasic convertase, and yeast endopeptidase-24.15 related peptidase. An active
      site-directed inhibitor of metalloendopeptidase-24.15, N-[1-(R,S)-carboxyl-3
      phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate also had no effects on the amidolytic
      activity of MEP. Based on the cleavage sites of bioactive peptides and processing
      sites of vitamin K-dependent proproteins, intramolecularly quenched fluorogenic
      peptide substrates were newly synthesized. Among the thirteen substrates used,
      the most reactive was 2-aminobenzoyl-Ala-Arg-Val-Arg-Arg-Ala- Asn-Ser-2,4
      dinitroanilinoethylamide (kcat/Km = 9.3 x 10(5) M-1.S-1). An angiotensin
      antagonist, [Sar1, Ala8]-angiotensin II, inhibited hydrolysis of the substrate by
      MEP in a competitive manner (Kl = 7.6 microM). MEP cleaved oligopeptides even on
      the carboxyl side of proline residue and these peptides are resistant to
      hydrolysis by the cytosol-derived proteasome, therefore MEP may participate in
      the catabolism of oligopeptides in the cytosol, together with other endo
      oligopeptidases.

PMID- 8576106
TI  - Dual roles of sphingolipids in signaling of the escape from and onset of
      apoptosis in a mouse cytotoxic T-cell line, CTLL-2.
AB  - In our previous study, the sphingosine-like immunosuppressant, ISP-1, was found
      to suppress the proliferation of an interleukin-2-dependent cytotoxic T cell
      line, CTLL-2, through the inhibition of serine palmitoyltransferase, which
      catalyzes the committed step of sphingolipid biosynthesis. Analysis of the effect
      of ISP-1 by flow cytometry revealed that the ISP-1-dependent decrease in cell
      number was not due to inhibition of the cell cycle progression of CTLL-2 cells
      but to the induction of apoptosis of the cells. The ISP-1-induced apoptosis was
      inhibited by the addition of sphingosine (2 microM), suggesting that this ISP-1
      induced apoptosis is triggered by the decrease in the intracellular levels of
      sphingolipids caused by the inhibition of serine palmitoyltransferase. However,
      another interleukin-2-dependent cell line, F7, which was derived from a mouse pro
      B cell line, did not show ISP-1-dependent apoptosis, indicating that the effect
      of ISP-1 may be specific for a certain type of T cell lineage such as CTLL-2. On
      the other hand, a high dose of sphingosine (5 microM) by itself induced the
      apoptosis of CTLL-2 cells. This sphingosine-dependent apoptosis was also observed
      with F7 cells. These results provide evidence that the intracellular levels of
      sphingolipids play an important role in the signaling of the escape from and
      onset of apoptosis of CTLL-2 cells.

PMID- 8576107
TI  - Activation of brain B-Raf protein kinase by Rap1B small GTP-binding protein.
AB  - Rap1 small GTP-binding protein has the same amino acid sequence at its effector
      domain as that of Ras. Rap1 has been shown to antagonize the Ras functions, such
      as the Ras-induced transformation of NIH 3T3 cells and the Ras-induced activation
      of the c-Raf-1 protein kinase-dependent mitogen-activated protein (MAP) kinase
      cascade in Rat-1 cells, whereas we have shown that Rap1 as well as Ras stimulates
      DNA synthesis in Swiss 3T3 cells. We have established a cell-free assay system in
      which Ras activates bovine brain B-Raf protein kinase. Here we have used this
      assay system and examined the effect of Rap1 on the B-Raf activity to
      phosphorylate recombinant MAP kinase kinase (MEK). Recombinant Rap1B stimulated
      the activity of B-Raf, which was partially purified from bovine brain and
      immunoprecipitated by an anti-B-Raf antibody. The GTP-bound form was active, but
      the GDP-bound form was inactive. The fully post-translationally lipid-modified
      form was active, but the unmodified form was nearly inactive. The maximum B-Raf
      activity stimulated by Rap1B was nearly the same as that stimulated by Ki-Ras.
      Rap1B enhanced the Ki-Ras-stimulated B-Raf activity in an additive manner. These
      results indicate that not only Ras but also Rap1 is involved in the activation of
      the B-Raf-dependent MAP kinase cascade.

PMID- 8576108
TI  - Distinct Ca(2+)-dependent properties of the first and second C2-domains of
      synaptotagmin I.
AB  - Synaptotagmin 1 (SytI) is a synaptic vesicle protein that binds Ca2+ and is
      essential for fast, Ca(2+)-dependent neurotransmitter release in the hippocampus,
      suggesting that it serves as a Ca2+ sensor for exocytosis. Although SytI has two
      cytoplasmic C2-domains, only the first C2-domain was shown to exhibit Ca2+
      regulation; it binds phospholipids and syntaxin in a Ca(2+)-dependent manner. By
      contrast, the second C2-domain is inactive in these assays and only binds
      putative interacting molecules in a Ca(2+)-independent manner. We have now
      discovered in a yeast two-hybrid screen for SytI-interacting molecules that the
      C2-domains of SytI interact with themselves. Using immobilized recombinant C2
      domains from SytI and SytII, we found that only the second but not the first C2
      domains of these synaptotagmins are capable of affinity-purifying native rat
      brain SytI and that this binding is Ca(2+)-dependent, suggesting that only the
      second C2-domain is capable of a Ca(2+)-triggered self-association. A relatively
      high Ca2+ concentration (> 100 microM) is required for binding in the presence of
      Mg2+; Sr2+ and Ba2+ but not Mg2+ can substitute for Ca2+. Our data suggest that
      the second C2-domain of SytI is also a Ca(2+)-regulated domain similar to the
      first C2-domain but with distinct binding activities.

PMID- 8576109
TI  - G(o)-protein alpha-subunits activate mitogen-activated protein kinase via a novel
      protein kinase C-dependent mechanism.
AB  - Mitogen-activated protein kinase (MAPK) is activated in response to both receptor
      tyrosine kinases and G-protein-coupled receptors. Recently, Gi-coupled receptors,
      such as the alpha 2A adrenergic receptor, were shown to mediate Ras-dependent
      MAPK activation via a pathway requiring G-protein beta gamma subunits (G beta
      gamma) and many of the same intermediates involved in receptor tyrosine kinase
      signaling. In contrast, Gq-coupled receptors, such as the M1 muscarinic
      acetylcholine receptor (M1AChR), activate MAPK via a pathway that is Ras
      independent but requires the activity of protein kinase C (PKC). Here we show
      that, in Chinese hamster ovary cells, the M1AChR and platelet-activating factor
      receptor (PAFR) mediate MAPK activation via the alpha-subunit of the G(o)
      protein. G(o)-mediated MAPK activation was sensitive to treatment with pertussis
      toxin but insensitive to inhibition by a G beta gamma-sequestering peptide (beta
      ARK1ct). M1AChR and PAFR catalyzed G(o) alpha-subunit GTP exchange, and MAPK
      activation could be partially rescued by a pertussis toxin-insensitive mutant of
      G(o) alpha but not by similar mutants of Gi. G(o)-mediated MAPK activation was
      insensitive to inhibition by a dominant negative mutant of Ras (N17Ras) but was
      completely blocked by cellular depletion of PKC. Thus, M1AChR and PAFR, which
      have previously been shown to couple to Gq, are also coupled to G(o) to activate
      a novel PKC-dependent mitogenic signaling pathway.

PMID- 8576110
TI  - Association of a 85-kDa serine kinase with activated fibroblast growth factor
      receptor-4.
AB  - Fibroblast growth factors (FGFs) transduce a variety of biological signals via
      four distinct tyrosine kinase receptors. We have characterized the
      phosphorylation of FGF receptor 4 (FGFR-4) and its association with a putative
      substrate, p85, using transfected L6 myoblast and NIH3T3 fibroblast cell lines.
      FGFR-4 was phosphorylated in vivo and in vitro mainly on serine and threonine
      residues in several peptides and to a lower degree on tyrosine residues. When
      analyzed further by in-gel kinase assay, immunoprecipitates of ligand-activated
      FGFR-4 contained a serine autophosphorylated polypeptide doublet of 85 kDa.
      Analysis of the major autophosphorylation site Y754F mutant of FGFR-4 showed that
      binding of p85 and its serine phosphorylation were independent of receptor
      autophosphorylation at this site. Okadaic acid treatment increased the basal
      autophosphorylation activity of p85 but decreased FGFR-4 tyrosine
      phosphorylation. In contrast, orthovanadate treatment increased the tyrosine
      phosphorylation of FGFR-4. These data show that a serine kinase is associated
      with activated FGFR-4 and suggest a role for serine phosphorylation in FGFR-4
      function.

PMID- 8576112
TI  - pp60v-src phosphorylates and activates low molecular weight phosphotyrosine
      protein phosphatase.
AB  - Low M(r) phosphotyrosine-protein phosphatase belongs to the non-receptor
      cytosolic phosphotyrosine-protein phosphatase subfamily. It has been demonstrated
      that this enzyme dephosphorylates receptor tyrosine kinases, namely the epidermal
      growth factor receptor in vitro and the platelet-derived growth factor receptor
      in vivo. Low M(r) phosphotyrosine-protein phosphatase is constitutively tyrosine
      phosphorylated in NIH/3T3 cells transformed by pp60v-src. The same tyrosine
      kinase, previously immunoprecipitated, phosphorylates this enzyme in vitro as
      well. Phosphorylation is enhanced using phosphatase inhibitors and phenylarsine
      oxide-inactivated phosphatase, consistently with the existence of an auto
      dephosphorylation process. Intermolecular dephosphorylation is demonstrated
      adding the active enzyme in a solution containing the inactivated and previously
      phosphorylated one. This tyrosine phosphorylation correlates with an increase in
      catalytic activity. Our results provide evidence of a physiological mechanism of
      low M(r) phosphotyrosine-protein phosphatase activity regulation.

PMID- 8576111
TI  - Identification of a physical interaction between calcineurin and nuclear factor
      of activated T cells (NFATp).
AB  - In T lymphocytes, the calcium/calmodulin-dependent serine/threonine phosphatase,
      calcineurin, plays a pivotal role in transducing membrane-associated signals to
      the nucleus. One of the putative targets of calcineurin is the pre-existing,
      cytosolic component of the nuclear factor of activated T cells (NFATp; also
      referred to as NFAT1), which is one of several transcription factors required for
      the expression of interleukin 2. Inhibition of calcineurin by the
      immunosuppressive drugs cyclosporin A and FK506 prevents dephosphorylation of
      NFATp and its translocation to the nucleus. However, a physical interaction
      between calcineurin and NFATp has not been demonstrated. Here we demonstrate the
      binding of NFATp from lysates of T cells to immobilized calcineurin. Stimulation
      of T cells with calcium ionophore induced a shift in the molecular weight of
      NFATp that is due to its dephosphorylation. This dephosphorylation was inhibited
      by treatment of T cells with cyclosporin A or FK506 prior to stimulation. Of
      note, both the phosphorylated and the dephosphorylated form of NFATp bound to
      calcineurin. Furthermore, the binding of both forms of NFATp to calcineurin was
      inhibited by pretreatment of calcineurin with a complex of FK506 and its ligand
      FKBP12. Taken together these data strongly suggest a direct interaction of
      calcineurin with NFATp and that this interaction does not depend upon the
      phosphorylation sites of NFATp affected by activation.

PMID- 8576113
TI  - A novel cysteine protease inhibitor of the egg of chum salmon, containing a
      cysteine-rich thyroglobulin-like motif.
AB  - ECI, one of three isoforms of cysteine protease inhibitor found in chum salmon
      eggs was purified to homogeneity, and its complete amino acid sequence was
      determined. The primary structure of ECI did not resemble those of other cysteine
      protease inhibitors of the cystatin superfamily but did resemble that of a
      cysteine-rich motif found as a repetitive structural element in thyroglobulin and
      several other proteins. The function of the cysteine-rich motif is not yet
      hypothesis. Two cysteine motif proteins, thyroglobulin and entactin, were tested
      for papain inhibitory activity and found to have none.

PMID- 8576115
TI  - Demonstration of a direct interaction between p56lck and the cytoplasmic domain
      of CD45 in vitro.
AB  - p56lck is a potential in vivo substrate for the tyrosine-specific phosphatase,
      CD45. In this study, recombinant purified p56lck was found to specifically
      associate with recombinant CD45 cytoplasmic domain protein, but not to the
      cytoplasmic domain of another related tyrosine phosphatase, receptor protein
      tyrosine phosphatase alpha. Under equilibrium binding conditions, the binding was
      saturable and occurred at a 1:1 molar stoichiometry. A fusion protein containing
      only the amino-terminal region of p56lck (residues 34-150) also bound to
      recombinant CD45, and further analysis of this region indicated that glutathione
      S-transferase fusion proteins of the unique amino-terminal region and the SH2
      domain, but not the SH3 domain of p56lck, bound to recombinant CD45. The SH2
      domain protein bound with a higher affinity than the amino-terminal region, but
      both were able to compete for the binding of p56lck to CD45, and when added
      together worked synergistically to compete for p56lck binding. The SH2 domain
      interaction with CD45 was specific as glutathione S-transferase-SH2 fusion
      proteins from p85 alpha subunit of phosphatidylinositol 3-kinase and SHC did not
      bind to CD45. In addition, this interaction occurred in the absence of any
      detectable tyrosine phosphorylation on CD45, suggesting a nonconventional SH2
      domain interaction.

PMID- 8576114
TI  - Effects of assembly and mutations outside the active site on the functional pH
      dependence of Escherichia coli aspartate transcarbamylase.
AB  - Electrostatics are central to the function and regulation of Escherichia coli
      aspartate transcarbamylase, and modeling has suggested that long range
      electrostatic effects are likely to be important (Glackin, M. P., McCarthy, M.
      P., Mallikarachchi, D., Matthew, J. B., and Allewell, N. M. (1989) Proteins
      Struct. Funct. Genet. 5, 66-77; Oberoi, H., Trikha, J., Yuan, X., and Allewell,
      N. M. (1995) Proteins Struct. Funct. Genet., in press). To investigate this
      possibility from an experimental standpoint, we have examined the effects both of
      assembly and of removing ionizable and polar side chains outside the active site
      (Glu-50, Tyr-165, and Tyr-240) on the pH dependence of the kinetic parameters of
      aspartate transcarbamylase. The holoenzyme (c6r6) assembles from three regulatory
      dimers (r2) and two catalytically active trimers (c3). pH dependences of the
      enzyme kinetic parameters suggest that the mechanisms of productive binding of L
      Asp to the binary complexes of the catalytic subunit (c3) and holoenzyme (c6r6)
      with carbamyl phosphate are different. In contrast, the Michaelis complex appears
      similar for both c3 and c6r6, except for pK shifts of approximately 1 pH unit.
      Results also indicate that the catalytic mechanism of the holoenzyme does not
      involve reverse protonation, as has recently been proposed for the catalytic
      trimer (Turnbull, J. L., Waldrop, G. L., and Schachman, H. K. (1992) Biochemistry
      31, 6562-6569). The tyrosines at positions 165 and 240 are part of a cluster of
      interactions that links the catalytic subunits in the T state (the cluc4
      interface) and which is disrupted in the T --> R transition. The effects of
      mutating the two Tyr residues are quite different: Y240F has higher than wild
      type activity and affinity over the entire pH range, while Y165F has activity and
      affinity an order of magnitude lower than wild-type. Removal of the regulatory
      subunits from Y165F increases activity and affinity and restores the pH
      dependence of the wild-type catalytic subunit. Like Y165F, E50A has low activity
      and affinity over the entire pH range. Linkage analysis indicates that there is
      long range energetic coupling among the active site, the ear subunit interfaces,
      and residue Y165. The substantial quantitative difference between Y165F and
      Y240F, both of which are at the c1:c4 interface about 14-16 A from the closest
      active site, demonstrates specific path dependence, as opposed to general
      distance dependence, of interactions between this interface and the active site.

PMID- 8576116
TI  - Identification of contact sites in the actin-thymosin beta 4 complex by distance
      dependent thiol cross-linking.
AB  - Binding sites of actin and thymosin beta 4 were investigated using a set of
      bifunctional thiol-specific reagents, which allowed the insertion of cross
      linkers of defined lengths between cysteine residues of the complexed proteins.
      After the cross-linkers were attached to actin specifically at either Cys10,
      Cys374, or the sulfur atom of the ATP analog adenosine 5'-O-(thiotriphosphate)
      (ATP gamma S), the actin derivatives were reacted with synthetic thymosin beta 4
      analogs containing a cysteine at one of the positions 6, 17, 28, 34, and 40.
      Immediate cross-linking as followed by UV spectroscopy was found for Cys374 of
      actin and Cys6 of thymosin beta 4, indicating that the N terminus of thymosin
      beta 4 is in close proximity (< or = 9.2 A) to the C terminus of actin. In
      contrast, only insignificant reactivity was measured for all thymosin beta 4
      analogs when the cross-linkers were anchored at Cys10 of actin. A second contact
      site was identified by cross-linking of Cys17 and Cys28 in thymosin beta 4 with
      the ATP gamma S derivative bound to actin, indicating that the hexamotif of
      thymosin beta 4 (positions 17-22) is in close proximity (< or = 9.2 A) to the
      nucleotide. The importance of the amino acids 17 and 28 in thymosin beta 4 for
      the interaction with actin was emphasized by the finding that thymosin analogs
      containing cysteine in these positions exhibited strongly reduced abilities to
      inhibit actin polymerization.

PMID- 8576117
TI  - Functional analysis of aquaporin-1 deficient red cells. The Colton-null
      phenotype.
AB  - The aquaporin-1 (AQP1) water transport protein contains a polymorphism
      corresponding to the Colton red blood cell antigens. To define the fraction of
      membrane water permeability mediated by AQP1, red cells were obtained from human
      kindreds with the rare Colton-null phenotype. Homozygosity or heterozygosity for
      deletion of exon I in AQP1 correlated with total or partial deficiency of AQP1
      protein. Homozygote red cell morphology appeared normal, but clinical laboratory
      studies revealed slightly reduced red cell life span in vivo; deformability
      studies revealed a slight reduction in membrane surface area. Diffusional water
      permeability (Pd) was measured under isotonic conditions by pulsed field gradient
      NMR. Osmotic water permeability (Pf) was measured by change in light scattering
      after rapid exposure of red cells to increased extracellular osmolality. AQP1
      contributes approximately 64% (Pd = 1.5 x 10(-3) cm/s) of the total diffusional
      water permeability pathway, and lipid permeation apparently comprises
      approximately 23%. In contrast, AQP1 contributes > 85% (Pf = 19 x 10(-3) cm/s) of
      the total osmotic water permeability pathway, and lipid permeation apparently
      comprises only approximately 10%. The ratio of AQP1-mediated Pf to Pd predicts
      the length of the aqueous pore to be 36 A.

PMID- 8576118
TI  - Folding-related dimerization of human cystatin C.
AB  - With the aim to improve our understanding of the structural basis for protein
      self-association and aggregation, in particular in relationship to protein
      refolding and amyloid formation, folding-related processes for human cystatin C
      have been studied. Using NMR spectroscopy together with chromatographic and
      electrophoretic methods, a self-association process resulting in dimer formation
      for protein samples treated with denaturing agents as well as for samples
      subjected to low pH or high temperature conditions could be studied with amino
      acid resolution. In all three cases, the dimerization involves properly folded
      molecules and proceeds via the reactive site of the inhibitor, which leads to
      complete loss of its biological activity. This dimerization process has potential
      relevance for amyloid formation by the brain hemorrhage-causing Leu58-Gln variant
      of cystatin C. The results also indicate that cystatin C dimerization and
      inactivation may occur in acidified compartments in vivo, which could be relevant
      for the physiological regulation of cysteine proteinase activity.

PMID- 8576119
TI  - Influence of Mg2+ on the structure and function of Rab5.
AB  - Mg2+ inhibits GDP release from Rab5WT but not from Rab5S34N, a mutant lacking
      Ser34 critical for Mg2+ coordination in the nucleotide binding pocket. Thus,
      inhibition of GDP release is apparently exerted via coordination of Mg2+ between
      Rab5 and GDP. Mg2+ also induces conformational changes in Rab5WT, demonstrated by
      increased tryptophan fluorescence intensity and a red shift in lambda max for the
      GDP-bound protein. Mg(2+)-induced fluorescence changes are not observed for
      Rab5S34N. The correlation between Mg2+ effects on nucleotide exchange and the
      fluorescence properties of Rab5 suggests that a conformation promoted through
      Mg2+ coordination with Ser34 also contributes to inhibition of GDP release. The
      role of structural changes in GDP release was investigated using C- and N
      terminal truncation mutants. Similar to Rab5WT, Mg2+ inhibits GDP release and
      alters the fluorescence of Rab5(1-198) but only partially inhibits release from
      Rab5(23-198) and fails to induce changes in the latter's fluorescence properties.
      Since Rab5(23-198) maintains Ser34 necessary for Mg2+ coordination, the lack of
      Mg(2+)-induced fluorescence changes suggests a requirement for the N-terminal
      domain to promote a conformation blocking GDP release. A model for mechanisms of
      interaction between Ras-like proteins and their exchange factors is proposed.

PMID- 8576120
TI  - Oxidation of low density lipoproteins greatly enhances their association with
      lipoprotein lipase anchored to endothelial cell matrix.
AB  - Native and oxidized low density lipoprotein retention within arterial wall
      endothelial cell matrix (ECM) is an early event in the pathogenesis of
      atherosclerosis. Previously we showed lipoprotein lipase (LPL) addition to ECM
      enhanced the retention of apoB-containing lipoproteins. In the present studies we
      examined whether the oxidation of low density lipoprotein (LDL) increases its
      retention by LPL-containing ECM. Except where noted, 125I-labeled moderately
      oxidized LDL (ModOxLDL) was prepared by long term storage of 125I-LDL. Without
      LPL, 125I-ModOxLDL matrix binding was low and nonsaturable. LPL preanchored to
      ECM resulted in 125I-ModOxLDL binding that was saturable and 20-fold greater than
      in the absence of LPL, with an association constant equal to 2.6 nM. Copper
      oxidized LDL (Cu-OxLDL) was able to compete with 125I-ModOxLDL, whereas a 60-fold
      native LDL excess had no effect. Reconstituted apolipoprotein B from Cu-OxLDL
      also reduced 125I-ModOxLDL to LPL, whereas liposomes derived from the lipid
      extract of Cu-OxLDL had no effect on binding. These data suggest that the
      increased binding of oxidized LDL to LPL-ECM may be due to the exposure of novel
      apoB binding sites and not an oxidized lipid moiety. 125I-ModOxLDL binding was
      also not affected by either preincubation with a 300-fold molar excess of apoE
      poor HDL or an 340-fold molar excess of Cu-Ox-HDL. In contrast, a 4-fold apoE
      rich HDL excess (based on protein) totally inhibited 125I-ModOxLDL matrix
      retention. Positively charged peptides of polyarginine mimicked the effect of
      apoE-rich HDL in reducing the 125I-ModOxLDL retention; however, polylysine had no
      effect. We postulate that the oxidation of LDL may be a mechanism that enhances
      LDL retention by the ECM-bound LPL and that the protective effects of apoE
      containing HDL may in part be due to its ability to block the retention of
      oxidized LDL in vivo.

PMID- 8576121
TI  - Calmodulin binds to the basolateral targeting signal of the polymeric
      immunoglobulin receptor.
AB  - We have identified a major calmodulin (CaM)-binding protein in rat liver
      endosomes using 125I-CaM overlays from two-dimensional protein blots.
      Immunostaining of blots demonstrates that this protein is the polymeric
      immunoglobulin receptor (pIgR). We further investigated the interaction between
      pIgR and CaM using Madin-Darby canine kidney cells stably expressing cloned wild
      type and mutant pIgR. We found that detergent-solubilized pIgR binds to CaM
      agarose in a Ca(2+)-dependent fashion, and binding is inhibited by the addition
      of excess free CaM or the CaM antagonist W-13 (N-(4-aminobutyl)-5-chloro-2
      naphthalenesulfonamide), suggesting that pIgR binding to CaM is specific.
      Furthermore, pIgR is the most prominent 35S-labeled CaM-binding protein in the
      detergent phase of Triton X-114-solubilized, metabolically labeled pIgR
      expressing Madin-Darby canine kidney cells. CaM can be chemically cross-linked to
      both solubilized and membrane-associated pIgR, suggesting that binding can occur
      while the pIgR is in intact membranes. The CaM binding site is located in the
      membrane-proximal 17-amino acid segment of the pIgR cytoplasmic tail. This region
      of pIgR constitutes an autonomous basolateral targeting signal. However, binding
      of CaM to various pIgR mutants suggests that CaM binding is not necessary for
      basolateral targeting. We suggest that CaM may be involved in regulation of pIgR
      transcytosis and/or signaling by pIgR.

PMID- 8576122
TI  - Differential effects of a Rab6 mutant on secretory versus amyloidogenic
      processing of Alzheimer's beta-amyloid precursor protein.
AB  - The Ras-related GTP-binding protein, Rab6, is localized in late Golgi
      compartments where it mediates intra-Golgi vesicular trafficking. Herein we
      report that coexpression of Alzheimer's beta-amyloid precursor protein (beta
      APP751) with a dominant-negative Rab6 mutant (Rab6N126I) in human embryonal
      kidney 293 cells causes an increase in secretion of the soluble amino-terminal
      exodomain (s-APP alpha) derived from non-amyloidogenic processing of beta-APP751
      by alpha-secretase. The effect was specific to Rab6N126I, since the corresponding
      mutation in Rab8 (i.e. Rab8N121I), which has been implicated in protein transport
      to the plasma membrane, caused a modest reduction in s-APP alpha secretion. While
      Rab6N126I stimulated secretion of APP alpha, the accumulation of amyloid beta
      peptide (A beta) in the medium was either moderately reduced or unaffected.
      Similar differential effects of Rab6N126I on secretion of s-APP alpha versus A
      beta were observed in cell cultures that were overproducing A beta after
      transfection with a plasmid encoding Swedish variant of beta APP751. Moreover,
      assays of medium from the latter cultures revealed a marked increase in secretion
      of s-APP alpha relative to s-APP beta (the immediate product derived from
      cleavage of beta APP by beta-secretase). The results indicate that vesicular
      transport events controlled by Rab6 occur at or near a critical juncture in the
      trans-Golgi network where beta APP is sorted into either the constitutive alpha
      secretase pathway or the amyloidogenic beta-secretase pathway.

PMID- 8576124
TI  - Inhibition of catechol O-methyltransferase-catalyzed O-methylation of 2- and 4
      hydroxyestradiol by quercetin. Possible role in estradiol-induced tumorigenesis.
AB  - Catecholestrogens have been postulated to mediate the induction of kidney tumors
      by estradiol in male Syrian hamsters. In this study, we examined the mechanism of
      inhibition by quercetin of the catechol O-methyltransferase-catalyzed O
      methylation of catecholestrogens as a basis for the previously reported
      enhancement of estradiol-induced tumorigenesis by this flavonoid. In hamsters
      treated with 50 micrograms of [6,7-3H]estradiol, quercetin increased
      concentrations of 2- and 4-hydroxyestradiol in kidney by 80 and 59%,
      respectively. In animals treated with two 10-mg estradiol implants, quercetin
      also decreased by 63-65% the urinary excretion of 2- and 4-hydroxyestradiol
      monomethyl ethers. Taken together, these results demonstrate the in vivo
      inhibition of the O-methylation of catecholestrogens by quercetin. S-Adenosyl-L
      homocysteine, produced by the methylation of catecholestrogens, noncompetitively
      inhibited the O-methylation of 2- and 4-hydroxyestradiol by hamster kidney
      cytosolic catechol O-methyltransferase (IC50 approximately 10-14 microM). Due to
      the rapid O-methylation of quercetin itself, quercetin decreased renal
      concentrations of S-adenosyl-L-methionine by approximately 25% in control or
      estradiol-treated hamsters and increased concentrations of S-adenosyl-L
      homocysteine by 5-15 nmol/g of wet tissue, which was estimated to cause a 30-70%
      inhibition of the enzymatic O-methylation of catecholestrogens. Quercetin or
      fisetin (a structural analog) inhibited the O-methylation of 2- and 4
      hydroxyestradiol by a competitive plus noncompetitive mechanism (IC50
      approximately 2-5 microM). These results suggest that the in vivo O-methylation
      of catecholestrogens is inhibited more by S-adenosyl-L-homocysteine than by
      quercetin. The accumulation of 2- and 4-hydroxyestradiol during co-administration
      of estradiol and quercetin may enhance metabolic redox cycling of
      catecholestrogens and thus estradiol-induced kidney tumorigenesis.

PMID- 8576123
TI  - Transcriptional regulation of the yeast DnaJ homologue SIS1.
AB  - The Saccharomyces cerevisiae SIS1 gene encodes an essential heat shock protein
      with similarity to the Escherichia coli DnaJ protein. In sis 1-85 and sis1-86
      mutants, the sis1 RNA is induced to high levels at room temperature and without
      heat shock. The presence of wild type SIS1 in the sis1-85 mutant represses the
      overexpression of SIS1-85 protein. Furthermore, overexpression of wild type SIS1
      reduces the beta-galactosidase activity expressed from a SIS1:lacZ fusion. These
      results suggest that SIS1 negatively regulates its own expression. The
      autoregulation of SIS1 transcription is mediated through a 39-base pair cis
      element containing the SIS1 heat shock element plus additional flanking sequences
      on one side. Although SIS1 transcription is constitutive, it is transiently
      induced upon heat shock. In addition, SIS1 transcription is regulated by SSA (a
      class of HSP70 proteins) function. The elevated transcription of SIS1 in ssa1
      ssa2 mutants is mediated solely through the SIS1 heat shock element. Therefore,
      the SIS1 autoregulatory element is different from the SSA-responsive element,
      suggesting that the mechanism involved in autoregulation of SIS1 is distinct from
      regulation of SIS1 by SSA proteins.

PMID- 8576125
TI  - Activation of the integrin alpha v beta 3 involves a discrete cation-binding site
      that regulates conformation.
AB  - "Activation" of integrins is involved in the dramatic transition of leukocytes
      and platelets from suspension to adhesion. The integrin alpha v beta 3 is not
      known to take part in this sort of transition, even though it shares its beta
      subunit with alpha IIb beta 3, the activable integrin on platelets. In the
      context of a constitutively adhered cell, changes in activation state may be more
      subtle in their effects, but nonetheless important in regulating cell behavior.
      We hypothesized that alpha v beta 3 can undergo conformational changes analogous
      to those associated with alpha IIb beta 3 activation. Accordingly, we examined
      alpha v beta 3 on the surface of M21 cells (a human melanoma cell line) and found
      that, like alpha IIb beta 3, it can undergo conformational changes upon binding
      of a ligand analog and can be activated for ligand binding and migration by a
      monoclonal antibody directed against beta 3. Modulation of the binding of this
      activating antibody, AP5, ligand binding, and antibody-mediated activation all
      are associated with a discrete cation-binding site shared in both alpha IIb beta
      3 and alpha v beta 3. Based on a measured Ki, this site has an apparent Kd for
      calcium of approximately 20 microM. At physiological levels of calcium, about 40%
      of the total alpha v beta 3 on a cell's surface is in a conformation detected by
      AP5. The data suggest a model for both alpha v beta 3 and alpha IIb beta 3
      function in which the molecule can exist in either of (at least) two
      conformational states, one stabilized either by AP5 or ligand binding, refractory
      to calcium binding, and enhanced for ligand recognition, the other stabilized by
      calcium binding and refractory to AP5 and ligand binding. Functional analysis
      suggests that AP5 activates alpha v beta 3 by preventing occupation of this
      calcium site, and that the activated form of alpha v beta 3 differs functionally
      from the basal form. The active form is more conducive to migration and the basal
      to tight adhesion.

PMID- 8576127
TI  - Conformational changes in the fibronectin binding MSCRAMMs are induced by ligand
      binding.
AB  - Bacterial adherence to host tissue involves specific microbial surface adhesins
      of which a subfamily termed microbial surface components recognizing adhesive
      matrix molecules (MSCRAMMs) specifically recognize extracellular matrix
      components. We now report on the biophysical characterization of recombinant
      fibronectin binding MSCRAMMs originating from several different species of Gram
      positive bacteria. The far-UV CD spectra (190-250 nm) of recombinant forms of the
      ligand binding domain of the MSCRAMMs, in a phosphate-buffered saline solution at
      neutral pH, were characteristic of a protein containing little or no regular
      secondary structure. The intrinsic viscosity of this domain was found to be the
      same in the presence or absence of 6 M guanidine hydrochloride, indicating that
      the native and denatured conformations are indistinguishable. On addition of
      fibronectin NH2 terminus as ligand to the recombinant adhesin there is a large
      change in the resulting far-UV CD difference spectra. At a 4.9 M excess of the
      NH2 terminus the difference spectra shifted to what was predominately a beta
      sheet conformation, as judged by comparison with model far-UV CD spectra. The
      fibronectin NH2-terminal domain undergoes a minute but reproducible blue-shift of
      its intrinsic tryptophan fluorescence on addition of rFNBD-A, which contains no
      tryptophan residues. Since this result indicates that there is no large change in
      the environment of the tryptophan residues of the NH2 terminus on binding, the
      large shift in secondary structure observed by CD analysis is attributed to
      induction of a predominately beta-sheet secondary structure in the adhesin on
      binding to fibronectin NH2 terminus.

PMID- 8576126
TI  - A monoclonal antibody enhances ligand binding of fibronectin MSCRAMM (adhesin)
      from Streptococcus dysgalactiae.
AB  - A monoclonal antibody 3A10, generated from a mouse immunized with the
      Streptococcus dysgalactiae fibronectin (Fn) binding protein FnbA, was isolated,
      and its effect on ligand binding by the antigen was examined. The epitope for
      3A10 was localized to a previously unidentified Fn binding motif (designated An)
      just N-terminal of the repeat domain which represents the primary ligand binding
      site on FnbA. Fn binding to Au was enhanced by 3A10 rather than inhibited. This
      effect was demonstrated in two different assays. First, in the presence of 3A10
      the Au-containing proteins and synthetic peptide more effectively competed with
      bacterial cells for binding to Fn. Second, 3A10 dramatically increased the
      binding of biotin-labeled forms of the Au-containing proteins to Fn immobilized
      on a blotting membrane. Pure 3A10 IgG did not recognize the antigen by itself,
      and Fn was required for the immunological interaction between the antibody and
      the epitope. This induction effect of Fn was shown in both Western blot and
      enzyme-linked immunosorbent assay in which immobilized Au-containing molecules
      were probed with 3A10 in the presence of varying concentrations of Fn.
      Specificity analyses of 3A10 revealed that the monoclonal also recognized a
      ligand binding motif in a Streptococcus pyogenes Fn binding MSCRAMM but not the
      corresponding motifs in two related adhesins from Staphylococcus aureus and S.
      dysgalactiae. Furthermore, 3A10 stimulated Fn binding by S. pyogenes cells. These
      results together with subsequent biophysical studies presented in the
      accompanying paper (House-Pomepeo, K., Xu, Y., Joh, D., Speziale, P., and Hook,
      M. (1996) J. Biol. Chem. 271, 1379-1384) indicate that the ligand binding sites
      of Fn binding MSCRAMMs have little or no secondary structure. However, on binding
      to Fn, they appear to undergo a structural rearrangement resulting in a defined
      structure rich in beta sheet and expressing a ligand-induced binding site for
      antibodies such as 3A10.

PMID- 8576128
TI  - Sp1 mediates glucose activation of the acetyl-CoA carboxylase promoter.
AB  - Acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in the biosynthesis of
      fatty acids, is induced in the presence of high glucose levels. The ACC gene
      contains two promoters: promoter I (PI) expression is inducible under lipogenic
      conditions, while promoter II (PII) expression, even though constitutively
      expressed in all tissues, is also controlled under various physiological
      conditions. Examination of the expression pattern of a series of deletion
      constructs of PII showed that the region from -340 to -249 was essential for ACC
      induction. In addition, by electrophoretic mobility shift assays, supershift
      assays, and DNase I footprinting studies, we have detected the binding of the
      transcription factor Sp1 at the two GC-rich sequences located within the -340 to 
      249 region of promoter II. Mutations at the GC-rich sequences prevented binding
      of Sp1, and the induction of the PII promoter was no longer observed.
      Cotransfection studies, in Drosophila Schneider SL2 cells, with the Sp1
      expression vector and PII-CAT constructs, have further confirmed the activation
      of promoter II by Sp1. In addition, we have identified Sp3, another member of the
      Sp1 family of transcription factors, as a second factor that can bind to the
      glucose response elements of PII.

PMID- 8576129
TI  - Calmodulin binds to specific sequences in the cytoplasmic domain of C-CAM and
      down-regulates C-CAM self-association.
AB  - C-CAM is a cell adhesion molecule belonging to the immunoglobulin supergene
      family and is known to mediate calcium-independent homophilic cell-cell binding.
      Two major isoforms, C-CAM1 and C-CAM2, which differ in their cytoplasmic domains,
      have been identified. Previous investigations have demonstrated that both
      cytoplasmic domains can bind calmodulin in a calcium-dependent reaction. In this
      investigation, peptides corresponding to the cytoplasmic domains of C-CAM were
      synthesized on cellulose membranes and used to map the binding sites for 125I
      labeled calmodulin. Both C-CAM1 and C-CAM2 had one strong calmodulin-binding site
      in the membrane-proximal region. Those binding regions were conserved in C-CAM
      from rat, mouse, and man. In addition, C-CAM1 from rat and mouse contained a
      weaker binding site in the distal region of the cytoplasmic domain. Biosensor
      experiments were performed to determine rate and equilibrium constants of the C
      CAM/calmodulin interaction. An association rate constants of 3.3 x 10(5) M-1 s-1
      and two dissociation rate constants of 2.2 x 10(-2) and 3.1 x 10(-5) s-1 were
      determined. These correspond to equilibrium dissociation constants of 6.7 x 10(
      8) and 9.4 x 10(-11) M, respectively. In dot-blot binding experiments, it was
      found that binding of calmodulin causes a down-regulation of the homophilic self
      association of C-CAM. This suggests that calmodulin can regulate the functional
      activity of C-CAM.

PMID- 8576130
TI  - Evidence that transmembrane segment 2 of the lactose permease is part of a
      conformationally sensitive interface between the two halves of the protein.
AB  - A conserved motif, GXXX(D/E)(R/K)XG(R/K)(R/K), is found in a large group of
      evolutionarily related membrane proteins involved in the transport of small
      molecules across the membrane. This motif is located within the cytoplasmic side
      of transmembrane domain 2 (TM-2) and extends through the hydrophilic loop that
      connects transmembrane domains 2 and 3. The motif is repeated again in the second
      half of the protein. In a previous study concerning the loop 2/3 motif (Jessen
      Marshall, A. E., Paul, N. J., and Brooker, R. J. (1995) J. Biol. Chem. 270, 16251
      16257), it was shown that the conserved aspartate at the fifth position in the
      motif is critical for transport activity since a variety of site-directed
      mutations were found to greatly diminish the rate of transport. In the current
      study, two of these mutations, in which the conserved aspartate was changed to
      threonine or serine, were used as parental strains to isolate second site
      suppressor mutations that restore transport function. A total of 10 different
      second site mutations were identified among a screen of 19 independent mutants.
      One of the suppressors was found within loop 1/2 in which Thr-45 was changed to
      arginine. Since the conserved aspartate and position 45 are at opposite ends of
      TM-2, these results suggest that the role of the conserved aspartate residue in
      loop 2/3 is to influence the topology of TM-2. Surprisingly, the majority of
      suppressor mutations were found in the second half of the permease. All of these
      are expected to alter helix topology in either of two ways. Some of the mutations
      involved residues within transmembrane segments 7 and 11 that produced
      substantial changes in side chain volume: TM-7 (Cys-234-->Trp or Phe, Gln-241-
      >Leu, and Phe-247-->Val) and TM-11 (Ser-366-->Phe). Alternatively, other
      mutations were highly disruptive substitutions at the ends of transmembrane
      segments or within hydrophilic loops (Gly-257-->Asp, Val-367-->Glu, Ala-369-
      >Pro, and a 5-codon insertion into loop 11/12). It is hypothesized that the
      effects of these suppressor mutations are to alter the helical topologies in the
      second half of the protein to facilitate a better interaction with the first
      half. Overall, these results are consistent with a transport model in which TM-2
      acts as an important interface between the two halves of the lactose permease.
      According to our tertiary model, this interaction occurs between TM-2 and TM-11.

PMID- 8576131
TI  - Immunochemical characterization and transacting properties of upstream
      stimulatory factor isoforms.
AB  - The ubiquitous upstream stimulatory factor (USF) transcription factors encoded by
      two distinct genes (USF1 and USF2) exist under the form of various dimers able to
      bind E-boxes. We report the molecular cloning and functional characterization of
      USF2 isoforms, corresponding to a 44-kDa subunit, USF2a, and a new 38-kDa
      subunit, USF2b, generated by differential splicing. Using specific anti-USF
      antibodies, we define the different binding complexes in various nuclear
      extracts. In vivo, the USF1/USF2a heterodimer represents over 66% of the USF
      binding activity whereas the USF1 and USF2a homodimers represent less than 10%,
      which strongly suggests an in vivo preferential association in heterodimers. In
      particular, an USF1/USF2b heterodimer accounted for almost 15% of the USF species
      in some cells. The preferential heterodimerization of USF subunits was reproduced
      ex vivo, while the in vitro association of cotranslated subunits, or recombinant
      USF proteins, appeared to be random. In transiently transfected HeLa or hepatoma
      cells, USF2a and USF1 homodimers transactivated a minimal promoter with similar
      efficiency, whereas USF2b, which lacks an internal 67-amino acid domain, was a
      poor transactivator. Additionally, USF2b was an efficient as USF1 and USF2a
      homodimers in transactivating the liver-specific pyruvate kinase gene promoter.

PMID- 8576132
TI  - Novel regulation of keratin gene expression by thyroid hormone and retinoid
      receptors.
AB  - Expression of keratin proteins, markers of epidermal differentiation and
      pathology, is uniquely regulated by the nuclear receptors for retinoic acid (RAR)
      and thyroid hormone (T3R) and their ligands: it is constitutively activated by
      unliganded T3R, but it is suppressed by ligand-occupied T3R or RAR. This
      regulation was studied using gel mobility shift assays with purified receptors
      and transient transfection assays with vectors expressing various receptor
      mutants. Regulation of keratin gene expression by RAR and T3R occurs through
      direct binding of these receptors to receptor response elements of the keratin
      gene promoters. The DNA binding "C" domain of these receptors is essential for
      both ligand-dependent and -independent regulation. However, the NH2-terminal
      "A/B" domain of T3R is not required for either mode of regulation of keratin gene
      expression. Furthermore, v-ErbA, an oncogenic derivative of cT3R, also activates
      keratin gene expression. In contrast to the previously described mechanism of
      gene regulation by T3R, heterodimerization with the retinoid X receptor is not
      essential for activation of keratin gene expression by unliganded T3R. These
      findings indicate that the mechanism of regulation of keratin genes by RAR and
      T3R differs significantly from the mechanisms described for other genes modulated
      by these receptors.

PMID- 8576133
TI  - Reverse phosphotransfer from OmpR to EnvZ in a kinase-/phosphatase+ mutant of
      EnvZ (EnvZ.N347D), a bifunctional signal transducer of Escherichia coli.
AB  - EnvZ of Escherichia coli is a transmembrane histidine kinase belonging to the
      family of two-component signal transducing systems prevalent in prokaryotes and
      recently discovered in eukaryotes. In response to changes in medium osmolarity
      EnvZ regulates the level of phosphorylated OmpR, its conjugate response
      regulating transcription factor for ompF and ompC genes. EnvZ has dual opposing
      enzymatic activities; OmpR-phosphorylase (kinase) and phospho-OmpR
      dephosphorylase (phosphatase). The osmotic signal is proposed to regulate the
      ratio of the kinase to the phosphatase activities of EnvZ to modulate the level
      of OmpR phosphorylation. In this work we used a COOH-terminal fragment of a
      previously identified kinase-/phosphatase+ EnvZ mutant (EnvZ-N347D) to
      demonstrate that the phosphoryl group on phospho-OmpR is transferred back to EnvZ
      to the same histidine residue (His243) that is utilized for the autokinase
      reaction by the wild type protein. Phospho-EnvZ-N347D thus formed could also
      transfer its phosphoryl group back to OmpR. The phosphotransfer reaction from
      phospho-OmpR to EnvZ.N347D was inhibited by ADP while Mg2+ ions stimulated the
      dephosphorylation reaction, resulting in release of inorganic phosphate. These
      results indicate that the energy levels of phosphoryl groups on OmpR and EnvZ are
      very similar and that the phosphatase reaction in the EnvZ.N347D mutant involves
      a reversal of the phosphotransfer reaction from EnvZ to OmpR using the identical
      His243 residue.

PMID- 8576134
TI  - Irreversible binding of cis-(+)-3-methylfentanyl isothiocyanate to the delta
      opioid receptor and determination of its binding domain.
AB  - Binding of cis-(+)-3-methylfentanyl isothiocyanate (SUPERFIT) to cloned opioid
      receptors stably expressed in Chinese hamster ovary cells was characterized.
      SUPERFIT inhibited [3H]diprenorphine binding with much higher affinity for the
      delta than the mu or kappa receptor. Pretreatment with SUPERFIT followed by
      extensive washing reduced delta binding with an IC50 value of 7.1 nM, yet it did
      not affect mu and kappa binding up to 0.1 microns. The reduction in delta binding
      by SUPERFIT pretreatment was due to a decrease in Bmax with no change in Kd.
      These results indicate that SUPERFIT is a highly selective delta irreversible
      ligand. We then determined the region in the delta receptor that confered binding
      selectivity for SUPERFIT by examining its binding to six mu/delta chimeric
      receptors. SUPERFIT bound to delta, mu/delta 1 (amino acids mu 1-94/delta 76
      372), delta/mu 3 (delta 1-134/mu 154-398), and delta/mu 4 (delta 1-187/mu 207
      398) receptors with high affinity but to mu, delta/mu 1 (delta 1-75/mu 95-398),
      mu/delta 3 (mu 1-153/delta 135-372), and mu/delta 4 (mu 1-206/delta 188-372)
      receptors with low affinity. Pretreatment with SUPERFIT potently inhibited
      [3H]diprenorphine binding to delta, mu/delta 1, delta/mu 3, and delta/mu 4 but
      affected binding to mu, delta/mu 1, mu/delta 3, and mu/delta 4 only at much
      higher concentrations. Thus, the segment from the beginning of the first
      intracellular loop to the middle of the third transmembrane helix of the delta
      receptor is important for selective binding of SUPERFIT.

PMID- 8576135
TI  - Monovalent cation activation and kinetic mechanism of inosine 5'-monophosphate
      dehydrogenase.
AB  - Human type II inosine 5'-monophosphate dehydrogenase has been purified to
      homogeneity from an Escherichia coli strain that express large quantities of the
      enzyme from the cloned gene. Steady state kinetic studies have been used to
      characterize the activation by monovalent cations, including Li+, Na+, K+, Rb+,
      Cs+, Tl+, NH4+, and N(CH3)4+. The enzyme has less than 1% of the maximal activity
      in the absence of an added monovalent cation, such as K+, Na+, Rb+, Tl+, or NH4+.
      The enzyme is activated by K+ and Tl+ at lower concentrations than those of other
      monovalent cations. Li+ and N(CH3)4+ do not activate the enzyme, nor do they
      inhibit the K(+)-activated enzyme, implying that ionic radius is important in
      binding selectivity. The Km values for both substrates and Vmax differ with
      different monovalent cations. Initial velocity and product inhibition kinetic
      data are consistent with an ordered steady state mechanism in which the enzyme
      binds K+ first, TMP second, and then NAD; the product NADH is released before
      xanthosine 5'-monophosphate. Substrate and product binding experiments support
      this mechanism and show the presence of one substrate binding site per subunit.
      Several rate constants were obtained from a computer simulation of the complete
      steady state rate equation.

PMID- 8576136
TI  - Identification of chitinase as the immunodominant filarial antigen recognized by
      sera of vaccinated rodents.
AB  - Acanthocheilonema viteae is a parasitic nematode of rodents. We identified the
      chitinase of A. viteae infective stage larvae (L3) as the main target of the
      humoral immune response of jirds, which were protected against challenge
      infection after vaccination with irradiation attenuated L3. The cDNA of the L3
      chitinase has been sequenced, and the deduced amino acid sequence shows
      significant homologies to chitinases of Brugia malayi microfilariae, insects,
      yeast, bacteria, and Streptomyces sp. The protein has been characterized by
      monoclonal antibodies and substrate activity gels. The chitinase of L3 may
      contribute to degrading the nematode cuticle during molting and thus represents a
      target of protective immune responses in a phase where the parasite is highly
      vulnerable. In addition, it has been shown that a similar enzyme exists in
      uterine microfilariae, which probably has a role in casting the egg shell.

PMID- 8576137
TI  - Differential effects of Moloney murine leukemia virus reverse transcriptase
      mutations on RNase H activity in Mg2+ and Mn2+.
AB  - We have previously described the in vitro and in vivo characterization of a panel
      of mutations affecting the RNase H domain of Moloney murine leukemia virus
      reverse transcriptase (Blain, S. W., and Goff, S.P. (1993) J. Biol. Chem. 268,
      23585-23592; Blain, S. W., and Goff, S. P. (1995) J. Virol. 69, 4440-4452). We
      were intrigued by a discrepancy between in vitro and in vivo RNase H results for
      two of the mutants. While delta C and delta 5E appeared to have nearly wild-type
      RNase H activity in vitro, they were unable to degrade their genomic RNA in vivo
      and thus were effectively RNase H null mutants in this context. In this present
      report, we describe the differential effects of these mutations on RNase H
      activity in vitro in the presence of Mg2+ versus Mn2+: mutants delta C and delta
      5E were active in the presence of the less biologically relevant Mn2+ and not in
      the presence of Mg2+. We also describe three mutants with only partial activity
      in Mg2+. The presence of the different cations can also affect DNA polymerization
      and processivity of an RNase H-deficient mutant.

PMID- 8576139
TI  - Conformational studies of glycopeptides by energy transfer. Introduction of
      fluorophore at specific branches of biantennary glycopeptides.
AB  - Biantennary glycopeptides from bovine fibrinogen were fluorescence labeled at
      each branch specifically for conformational studies by fluorescence energy
      transfer. Glycopeptides (by Pronase digestion) were separated by anion-exchange
      chromatography based on the degree of sialylation. The major monosialyl
      biantennary glycopeptides (see below) were used as substrates for galactose
      oxidase and periodate oxidation. [Formula: See Text] Galactose oxidase was used
      to oxidize the terminal Gal6' located on the Man alpha(1-6)Man branch. The
      oxidized glycopeptides (containing 6-oxo-galactose) were modified with 2
      (dansylamido)ethylamine by reductive amination. The N terminus of the peptide
      portion was then modified with naphthylacetic acid. Alternatively, the peptide
      portion of the monosialylated glycopeptide was first modified with naphthylacetic
      acid and the sialic acid located on the Man alpha(1-3)Man branch was oxidized
      with periodate under controlled conditions. The oxidized glycopeptides (oxo
      sialic acid) were coupled with 2-(dansylamido)ethylamine by reductive amination.
      These doubly fluorescence-labeled glycopeptides were used for conformational
      studies of biantennary glycopeptides by energy transfer (see the accompanying
      article (Wu, P., Lee, K. B., Lee, Y. C., and Brand, L. (1996) J. Biol. Chem. 271,
      1470-1474). Furthermore, the unmodified branch of the fluorescent labeled
      glycopeptides were digested stepwise with exoglycosidases. Resonance energy
      transfer experiments were done with each of the resulting derivatives to
      determine the effects of removing sugars at each stage of peeling on any
      conformational change on the resulting branch antennae.

PMID- 8576138
TI  - Endogenous reactive oxygen intermediates activate tyrosine kinases in human
      neutrophils.
AB  - In response to invading microorganisms, neutrophils produce large amounts of
      superoxide and other reactive oxygen intermediates (ROI) by assembly and
      activation of a multicomponent enzyme complex, the NADPH oxidase. While
      fulfilling a microbicidal role, ROI have also been postulated to serve as
      signaling molecules, because activation of the NADPH oxidase was found to be
      associated with increased tyrosine phosphorylation (Fialkow, L., Chan, C. K.,
      Grinstein, S., and Downey, G.P. (1993) J. Biol. Chem. 268, 17131-17137). The
      mechanism whereby ROI induces phosphotyrosine accumulation was investigated using
      electroporated neutrophils stimulated with guanosine 5'-O-3-thiotriphosphate in
      order to bypass membrane receptors. In vitro immune complex assays and
      immunoblotting were used to identify five tyrosine kinases present in human
      neutrophils. Of these, p56/59hck, p72syk, and p77btk were activated during
      production of ROI. Interestingly, the in vitro autophosphorylation activities of
      p53/56lyn and p59fgr were found to decline with ROI production. The mode of
      regulation of p56/59hck was explored in detail. Oxidizing agents were unable to
      activate p56/59hck in vitro and, once activated in situ, reducing agents failed
      to inactivate it, suggesting that the effects of ROI are indirect. Tyrosine
      phosphorylation of p56/59hck paralleled its activation, and dephosphorylation in
      vitro reversed the stimulation. We therefore conclude that tyrosine
      phosphorylation is central to the regulation of p56/59hck and likely also of
      p72syk, which is similarly phosphorylated upon activation of the oxidase. Because
      ROI have been shown to reduce the activity of tyrosine phosphatases, we suggest
      that this inhibition allows constitutively active kinases to
      auto/transphosphorylate on stimulatory tyrosine residues, leading to an increase
      in their catalytic activity. Enhanced phosphotyrosine accumulation would then
      result from the combined effects of increased phosphorylation with decreased
      dephosphorylation.

PMID- 8576140
TI  - Solution conformations of a biantennary glycopeptide and a series of its
      exoglycosidase products from sequential trimming of sugar residues.
AB  - Linkages between sugar residues in branched oligosaccharides exhibit various
      degrees of flexibility. This flexibility, together with other forces, determines
      the overall solution conformation of oligosaccharides. We used the method of time
      resolved resonance energy transfer to study the solution conformations of a
      biantennary glycopeptide and its partially trimmed products by exoglycosidases.
      The N-terminal of the glycopeptide was labeled with 2-naphthyl acetic acid as a
      fluorescent donor. Either terminal sugar residue, Gal6', on the branch bearing 6
      linked Man (antenna 6'), or Neu5Ac on the branch bearing 3-linked Man (antenna 6)
      was labeled with 5-dimethylaminophthalene-1-sulfonyl as an acceptor. The distance
      and distance distributions between the terminals were measured. In the intact
      biantennary glycopeptide, the donor-acceptor distance distribution of antenna 6'
      is bimodal with a majority of the population in the extended conformation and
      that of antenna 6 in one very broad population. The Neu5Ac on antenna 6 is
      oriented toward the N-terminal at low temperature and adopts a more extended form
      at high temperature. The removal of individual sugar residues along one of the
      two antenna in the biantennary oligosaccharide has a small effect on the distance
      distribution of the remaining antenna for both antennae 6 and 6'. Together with
      previous studies of the triantennary glycopeptides (Rice, K. G., Wu, P. G.,
      Brand, L., and Lee, Y.C. (1993) Biochemistry 32, 7264-7270), our results suggest
      that both steric hindrance and inter-residue hydrogen bonding are very important
      in the folding pattern in oligosaccharide structures.

PMID- 8576141
TI  - Conversion of chlorophyll b to chlorophyll a via 7-hydroxymethyl chlorophyll.
AB  - Chlorophyll b is synthesized from chlorophyll a by the oxidation of the methyl
      group on the ring B of the tetrapyrrole ring to the formyl group. Previously, we
      reported that chlorophyllide b could be converted to chlorophyll a in isolated
      cucumber etioplasts indicating the conversion of chlorophyll b to chlorophyll a.
      To identify the intermediate molecule, we used barley etioplasts instead of
      cucumber. Chlorophyll a and an additional pigment were found after incubation of
      chlorophyllide b with isolated barley etioplasts. The pigment has the same
      retention time and absorption spectrum as 7-hydroxymethyl chlorophyll, which has
      the hydroxymethyl group on ring B instead of the formyl group of chlorophyll b.
      Authentic 7-hydroxymethyl chlorophyll was prepared by reduction of chlorophyll b
      by NaBH4. Chlorophyll a accumulated during the incubation of 7-hydroxymethyl
      chlorophyllide with etioplasts. These findings indicate that chlorophyll b is
      converted to chlorophyll a via 7-hydroxymethyl chlorophyll. Chlorophyll b and 7
      hydroxymethyl chlorophyll accumulated within a short period of incubation of
      chlorophyllide b with etioplasts. However, chlorophyll a accumulated with a
      concomitant decrease of chlorophyll b and 7-hydroxymethyl chlorophyll. These
      observations also suggest that chlorophyll b is converted to 7-hydroxymethyl
      chlorophyll and then to chlorophyll a. Both steps required ATP.

PMID- 8576142
TI  - Sialylated oligosaccharide-specific plant lectin from Japanese elderberry
      (Sambucus sieboldiana) bark tissue has a homologous structure to type II ribosome
      inactivating proteins, ricin and abrin. cDNA cloning and molecular modeling
      study.
AB  - Bark lectins from the elderberry species belonging to the genus Sambucus have a
      unique carbohydrate binding specificity for sialylated glycoconjugates containing
      NeuAc(alpha 2-6)Gal/GalNAc sequence. To elucidate the structure of the elderberry
      lectin, a cDNA library was constructed from the mRNA isolated from the bark
      tissue of Japanese elderberry (Sambucus sieboldiana) with lambda gt11 phage and
      screened with anti-S. sieboldiana agglutinin (SSA) antibody. The nucleotide
      sequence of a cDNA clone encoding full-length SSA (LecSSA1) showed the presence
      of an open reading frame with 1902 base pairs, which corresponded to 570 amino
      acid residues. This open reading frame encoded a signal peptide and a linker
      region (19 amino acid residues) between the two subunits of SSA, the hydrophobic
      (A-chain) and hydrophilic (B-chain) subunits. This indicates that SSA is
      synthesized as a preproprotein and post-translationally cleaved into two mature
      subunits. Homology searching as well as molecular modeling studies unexpectedly
      revealed that each subunit of SSA has a highly homologous structure to the
      galactose-specific lectin subunit and ribosome-inactivating subunit of plant
      toxic proteins such as ricin and abrin, indicating a close evolutionary
      relationship between these carbohydrate-binding proteins.

PMID- 8576143
TI  - Translational regulation of chloroplast genes. Proteins binding to the 5'
      untranslated regions of chloroplast mRNAs in Chlamydomonas reinhardtii.
AB  - We have examined the effects of illumination, carbon source, and levels of
      chloroplast protein synthesis on trans-acting proteins that bind to the leaders
      of five representative chloroplast mRNAs. The accumulation of these five
      chloroplast mRNAs and the proteins they encode were measured in cells grown under
      identical conditions. Extracts from all cell types examined contain a minimum set
      of six chloroplast 5'-untranslated region (UTR)-binding proteins (81, 62, 56, 47,
      38, and 15 kDa). Fractionation results suggest that multiple forms of the 81-, 62
      , and 47-kDa proteins may exist. A 36-kDa protein was found in all cells except
      those deficient in chloroplast protein synthesis. Binding of the 81-, 47-, and 38
      kDa proteins to the rps12 leader is effectively competed by the atpB or rbcL 5'
      UTRs, indicating that the same proteins bind to all three leaders. In contrast,
      these three proteins do not bind to the nuclear-encoded alpha-1 tubulin leader,
      which bound novel proteins of 110, 70, and 43 kDa. Cis-acting sequences within
      the 5'-UTRs of two chloroplast mRNAs (rps7 and atpB) have been identified which
      are protected from digestion by RNase T1 by extracts enriched for the 81-, 47-,
      and 38-kDa proteins.

PMID- 8576144
TI  - The metal ion-induced cooperative binding of HIV-1 integrase to DNA exhibits a
      marked preference for Mn(II) rather than Mg(II).
AB  - In this investigation, we examine the interaction between the human
      immunodeficiency virus type I integrase and oligonucleotides that reflect the
      sequences of the extreme termini of the viral long terminal repeats (LTRs). The
      results of gel filtration and a detailed binding density analysis indicate that
      the integrase binds to the LTR as a high-order oligomer at a density equivalent
      to 10 +/- 0.8 integrase monomers per 21-base pair LTR. The corresponding binding
      isotherm displays a Hill coefficient of 2, suggesting that the binding mechanism
      involves the cooperative interaction between two oligomers. This interaction is
      quite stable, exhibiting a prolonged half-life (t1/2 approximately 13 h) in the
      presence of Mn2+ cations. Complexes were less stable when formed with Mg2+ (t1/2
      approximately 1 h). The role of Mn2+ appears to be in the induction of the
      protein-protein interactions that stabilize the bound complexes. In terms of the
      3'-end processing of the LTR, similar catalytic rates (kcat approximately 0.06
      min-1) were obtained for the stable complex in the presence of either cation.
      Hence, the apparent preference observed for Mn2+ in standard in vitro integration
      assays can be attributed entirely to the augmentation in the DNA binding affinity
      of the integrase.

PMID- 8576145
TI  - Polar residues in the transmembrane domains of the type 1 angiotensin II receptor
      are required for binding and coupling. Reconstitution of the binding site by co
      expression of two deficient mutants.
AB  - Type 1 angiotensin receptors (AT1) are G-protein coupled receptors, mediating the
      physiological actions of the vasoactive peptide angiotensin II. In this study,
      the roles of 7 amino acids of the rat AT1A receptor in ligand binding and
      signaling were investigated by performing functional assays of individual
      receptor mutants expressed in COS and Chinese hamster ovary cells. Substitutions
      of polar residues in the third transmembrane domain with Ala indicate that
      Ser105, Ser107, and Ser109 are not essential for maintenance of the angiotensin
      II binding site. Replacement of Asn111 or Ser115 does not alter the binding
      affinity for peptidic analogs, but modifies the ability of the receptor to
      interact with AT1 (DuP753)- or AT2 (CGP42112A)-specific ligands. These 2 residues
      are probably involved in determining the binding specificity for these analogs.
      The absence of G-protein coupling to the Ser115 mutant suggests that this
      residue, in addition to previously identified residues, Asp74 and Tyr292,
      participates in the receptor activation mechanism. Finally, Lys102 (third helix)
      and Lys199 (fifth helix) mutants do not bind angiotensin II or different analogs.
      Co-expression of these two deficient receptors permitted the restoration of a
      normal binding site. This effect was not due to homologous recombination of the
      cDNAs but to protein trans-complementation.

PMID- 8576146
TI  - Aggregation of the Fc epsilon RI in mast cells induces the synthesis of Fos
      interacting protein and increases its DNA binding-activity: the dependence on
      protein kinase C-beta.
AB  - The ability of c-Fos to dimerize with various proteins creates transcription
      complexes which can exert their regulatory function on a variety of genes. One of
      the transcription factors that binds to c-Fos is the newly discovered Fos
      interacting protein (FIP). In this report we present evidence for the regulation
      of the synthesis of FIP by a physiological stimulus. We found that the
      aggregation of the mast cell high affinity receptor for IgE (Fc epsilon RI)
      induced the synthesis of FIP and increased its DNA binding activity. Moreover,
      down-regulation of the isoenzyme protein kinase C-beta (PKC-beta) by a specific
      antisense phosphorothioate oligonucleotide resulted in profound inhibition of FIP
      Fos DNA binding activity. Thus, aggregation of the Fc epsilon RI on mast cells
      elicits a PKC-beta dependent signaling pathway which regulates FIP-Fos DNA
      binding activity.

PMID- 8576147
TI  - Single amino acid substitutions in proteins of the armadillo gene family abolish
      their binding to alpha-catenin.
AB  - Analysis of the calcium-dependent cell adhesion molecule E-cadherin has led to
      the identification of catenins, which are necessary for cadherin function.
      Growing evidence that cadherins and catenins are subjected to genetic alterations
      in carcinogenesis makes it especially important to understand protein-protein
      interactions within the cadherin-catenin complex. Here we report the
      identification and analysis of the alpha-catenin binding site in plakoglobin
      (gamma-catenin). Using N- and C-terminal truncations of plakoglobin, we
      identified a domain of 29 amino acids necessary and sufficient for binding alpha
      catenin. The alpha-catenin binding site is fully encoded within exon 3 of
      plakoglobin but only partially represented in Armadillo repeat 1. This suggests
      that exons rather than individual Arm repeats encode functional domains of
      plakoglobin. Site-directed mutagenesis identified residues in the alpha-catenin
      binding site indispensable for binding in vitro. Analogous mutations in beta
      catenin and Armadillo had identical effects. Our results indicate that single
      amino acid mutations in the alpha-catenin binding site of homologs of Armadillo
      could prevent a stable association with alpha-catenin, thus affecting cadherin
      mediated adhesion.

PMID- 8576148
TI  - Analysis by surface plasmon resonance of the influence of valence on the ligand
      binding affinity and kinetics of an anti-carbohydrate antibody.
AB  - The kinetics of ligand binding by Se155-4, an antibody specific for the
      Salmonella serogroup B O-polysaccharide, were studied by surface plasmon
      resonance. Because trace amounts of oligomers in Fab and single-chain antibody
      variable domain (scFv) preparations resulted in biphasic binding profiles that
      were difficult to analyze, all kinetic measurements were performed on purified
      monomeric fragments and, for certain mutant scFv, dimeric forms. Results obtained
      with monomeric forms indicated that the relatively low affinity of the antibody
      was due to rapid dissociation (koff approximately 0.25 s-1). Dimeric forms
      generally showed off-rates that were approximately 20-fold slower and a 5-fold
      increase in association rate constants to approximately 2 x 10(5) M-1 s-1.
      Although the association phases for scFv dimers showed good curve fitting to a
      one component interaction model, the dissociation phases were biphasic,
      presumably because the availability and accessibility of sites on the antigen
      always leads to some monovalent attachment. The fast off-rate for dimers was the
      same as the monomer off-rate. Se155-4 IgG off-rates were very similar to those
      observed for scFv dimer, whereas the onrate was the same as that obtained with
      Fab and scFv monomer.

PMID- 8576149
TI  - Tyrosine phosphorylation of the c-cbl proto-oncogene product mediated by cell
      surface antigen CD38 in HL-60 cells.
AB  - The human cell surface antigen CD38 is a 46-kDa type II transmembrane
      glycoprotein with a short N-terminal cytoplasmic domain and a long Cys-rich C
      terminal extracellular one. We demonstrated previously that the extracellular
      domain of CD38 has NAD+ glycohydrolase (NADase) activity and that the ecto-form
      NADase activity induced in HL-60 cells during cell differentiation by retinoic
      acid is due to CD38. In the present study, we investigated the intracellular
      signaling mediated by CD38 in retinoic acid-differentiated HL-60 cells with an
      anti-CD38 monoclonal antibody. The addition of anti-CD38 monoclonal antibody to
      the cells induced rapid tyrosine phosphorylation of the cellular proteins with
      molecular weights of 120,000, 87,000, and 77,000. An increase in tyrosine kinase
      activity in the anti-phosphotyrosine immunoprecipitates of the cells was also
      observed after the addition of anti-CD38 monoclonal antibody. Moreover, one of
      the prominent tyrosine-phosphorylated proteins stimulated by the anti-CD38
      monoclonal antibody was identified as the c-cbl proto-oncogene product, p120c
      cbl. These results indicated that tyrosine phosphorylation of cellular proteins,
      including p120c-cbl, is possibly involved in transmembrane signaling mediated by
      CD38.

PMID- 8576150
TI  - Interaction of cyclin-dependent kinase 5 (Cdk5) and neuronal Cdk5 activator in
      bovine brain.
AB  - Neuronal cdc2-like kinase (Nclk) purified from bovine brain is a heterodimer of
      Cdk5 and an essential 25-kDa regulatory subunit (Lew, J., and Wang, J. H. (1995)
      Trends Biochem. Sci. 20, 33-37). The regulatory subunit is an N-terminal
      truncated derivative of a 35-kDa protein expressed specifically in brain, hence
      the name neuronal Cdk5 activator, p25/p35nck5a. In this study, we probe the
      relationship between the two different forms of Nck5a and their interaction with
      and activation of Cdk5 in bovine brain extract. Using protein fractionation
      procedures in combination with Western blot analysis and protein kinase assay,
      three forms of Cdk5 have been detected in bovine brain: a monomeric Cdk5 that can
      be activated by bacterially expressed GST-p21nck5a, a heterodimer of Cdk5 and
      p25nck5a that displays high kinase activity, and a Cdk5.p35nck5a complex that is
      inactive and refractory to GST-p21nck5a activation. Analysis of the Cdk5.p35nck5a
      complex by gel filtration chromatography indicated that the complex was part of a
      macromolecular structure with a molecular mass of approximately 670 kDa. When the
      macromolecular complex was subjected to gel filtration chromatography in the
      presence of 10% ethylene glycol, the fractions containing both p35nck5a and Cdk5,
      although eluting at the same position as control, displayed high kinase activity.
      The result is compatible with the suggestion that the macromolecular complex
      contained a kinase inhibitory factor that dissociated from the complex in 10%
      ethylene glycol.

PMID- 8576151
TI  - Biochemical characterization of human collagenase-3.
AB  - The cDNA of a novel matrix metalloproteinase, collagenase-3 (MMP-13) has been
      isolated from a breast tumor library (Freije, J. M. P., Dicz-Itza, I., Balbin,
      M., Sanchez, L. M., Blasco, R., Tolivia, J., and Lopez-Otin, C. (1994) J. Biol.
      Chem. 269, 16766-16773), and a potential role in tumor progression has been
      proposed for this enzyme. In order to establish the possible role of collagenase
      3 in connective tissue turnover, we have expressed and purified recombinant human
      procollagenase-3 and characterized the enzyme biochemically. The purified
      procollagenase-3 was shown to be glycosylated and displayed a M(r) of 60,000, the
      N-terminal sequence being LPLPSGGD, which is consistent with the cDNA-predicted
      sequence. The proenzyme was activated by p-aminophenylmercuric acetate or
      stromelysin, yielding an intermediate form of M(r) 50,000, which displayed the N
      terminal sequence L58EVTGK. Further processing resulted in cleavage of the Glu84
      Tyr85 peptide bond to the final active enzyme (M(r) 48,000). Trypsin activation
      of procollagenase-3 also generated a Tyr85 N terminus, but it was evident that
      the C-terminal domain was rapidly lost, and hence the collagenolytic activity
      diminished. Analysis of the substrate specificity of collagenase-3 revealed that
      soluble type II collagen was preferentially hydrolyzed, while the enzyme was 5 or
      6 times less efficient at cleaving type I or III collagen. Fibrillar type I
      collagen was cleaved with comparable efficiency to the fibroblast and neutrophil
      collagenases (MMP-1 and MMP-8), respectively. Unlike these collagenases, gelatin
      and the peptide substrates Mea-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 and Mca-Pro-Cha
      Gly-Nva-His-Ala-Dpa-NH2 were efficiently hydrolyzed as well, as would be
      predicted from the similarities between the active site sequence of collagenase-3
      (MMP-13) and the gelatinases A and B. Active collagenase-3 was inhibited in a 1:1
      stoichiometric fashion by the tissue inhibitors of metalloproteinases, TIMP-1,
      TIMP-2, and TIMP-3. These results suggest that in vivo collagenase-3 could play a
      significant role in the turnover of connective tissue matrix constituents.

PMID- 8576152
TI  - Circular dichroism and x-ray spectroscopies of Azotobacter vinelandii nitrogenase
      iron protein. MgATP and MgADP induced protein conformational changes affecting
      the [4Fe-4S] cluster and characterization of a [2Fe-2S] form.
AB  - Nucleotide interactions with nitrogenase are a central part of the mechanism of
      nitrogen reduction. Previous studies have suggested that MgATP or MgADP binding
      to the nitrogenase iron protein (Fe protein) induce protein conformational
      changes that control component protein docking, interprotein electron transfer,
      and substrate reduction. In the present study, we have investigated the effects
      of MgATP or MgADP binding to the Azotobacter vinelandii nitrogenase Fe protein on
      the properties of the [4Fe-4S] cluster using circular dichroism (CD) and x-ray
      absorption spectroscopies. Previous CD and magnetic CD studies on nitrogenase Fe
      protein suggested that binding of either MgATP or MgADP to the Fe protein
      resulted in identical changes in the CD spectrum arising from transitions of the
      [4Fe-4S]2+ cluster. We present evidence that MgADP or MgATP binding to the
      oxidized nitrogenase Fe protein results in distinctly different CD spectra,
      suggesting distinct changes in the environment of the [4Fc-4S] cluster. The
      present results are consistent with previous studies such as chelation assays,
      electron paramagnetic resonance, and NMR, which suggested that MgADP or MgATP
      binding to the nitrogenase Fe protein induced different conformational changes.
      The CD spectrum of a [2Fe-2S]2+ form of the nitrogenase Fe protein was also
      investigated to address the possibility that the MgATP- or MgADP-induced changes
      in the CD spectrum of the native enzyme were the result of a partial conversion
      from a [4Fe-4S] cluster to a [2Fe-2S] cluster. No evidence was found for a
      contribution of a [2Fe-2S]2+ cluster to the CD spectrum of oxidized Fe protein in
      the absence or presence of nucleotides. A novel two-electron reduction of the
      [2Fe-2S]2+ cluster in Fe protein was apparent from absorption, CD, and electron
      paramagnetic resonance data. Fe K-edge x-ray absorption spectra of the oxidized
      Fe protein revealed no changes in the structure of the [4Fe-4S] cluster upon
      MgATP binding to the Fe protein. The present results reveal that MgATP or MgADP
      binding to the oxidized state of the Fe protein result in different
      conformational changes in the environment around the [4Fe-4S] cluster.

PMID- 8576153
TI  - pH- and Ca(2+)-dependent aggregation property of secretory vesicle matrix
      proteins and the potential role of chromogranins A and B in secretory vesicle
      biogenesis.
AB  - Chromogranins A and B (CGA and CGB), the major proteins of the secretory vesicles
      of the regulated secretory pathway, have been shown to aggregate in a low pH and
      high calcium environment, the condition found in the trans-Golgi network where
      secretory vesicles are formed. Moreover, CGA and CGB, as well as several other
      secretory vesicle matrix proteins, have recently been shown to bind to the
      vesicle membrane at the intravesicular pH of 5.5 and to be released from it at a
      near physiological pH of 7.5. The pH- and Ca(2+)-dependent aggregation and
      interaction of chromogranins, as well as several other matrix proteins, with the
      vesicle membrane are considered essential in vesicle biogenesis. Therefore, to
      gain further insight into how vesicle matrix proteins find their way into the
      secretory vesicles, the pH- and Ca(2+)-dependent aggregation and vesicle membrane
      binding properties of the vesicle matrix proteins were studied, and it was found
      that most of the vesicle matrix proteins aggregated in the presence of Ca2+ at
      the intravesicular pH of 5.5. Furthermore, most of the vesicle matrix proteins
      bound not only to the vesicle membrane but also to CGA at pH 5.5, with the
      exception of a few matrix proteins that appeared to bind only to CGA or to
      vesicle membrane. Purified CGB was also shown to interact with CGA at pH 5.5. The
      extent and Ca(2+)-sensitivity of the aggregation of vesicle matrix proteins lay
      between those of purified CGB and CGA, CGB aggregation showing the highest degree
      of aggregation and being the most Ca2+ sensitive at a given protein
      concentration. Hence, in view of the abundance of chromogranins in secretory
      vesicles and their low pH- and high calcium-dependent aggregation property,
      combined with their ability to interact with both the vesicle matrix proteins and
      the vesicle membrane, CGA and CGB are proposed to play essential roles in the
      selective aggregation and sorting of potential vesicle matrix proteins to the
      immature secretory vesicles of the regulated secretory pathway.

PMID- 8576154
TI  - Mechanism of inhibition by arachidonic acid of the catalytic activity of Ras
      GTPase-activating proteins.
AB  - Ras is a guanine nucleotide-binding protein that acts as a molecular switch
      controlling cell growth. The Ras GTPase-activating proteins (GAPs) p120-GAP and
      neurofibromin are candidates as Ras effectors. The GTPase-activating activity of
      both proteins is inhibited by mitogenic lipids, such as arachidonic acid and
      phosphatidic acid, and differential inhibition of the two GAPs led to the
      hypothesis that both were effectors in a Ras-controlled mitogenic pathway
      (Bollag, G., and McCormick, F. (1991) Nature 351, 576-579). We have studied the
      mechanism of inhibition by arachidonic acid in three ways: first, by measurements
      of catalytic activity under multiple turnover conditions; second, using p-((6
      phenyl)-1,3,5-hexatrienyl)benzoic acid as a fluorescent probe for ligands binding
      to GAPs; and third, by using a scintillation proximity assay to measure direct
      binding of Ras to neurofibromin. We found no significant differential inhibition
      between p120-GAP and neurofibromin by arachidonic acid. The inhibition by
      arachidonic acid included a major component that is competitive with Ras GTP.
      These data suggest that insomuch as the mitogenic effects of lipids are mediated
      via inhibition of GAPs, GAPs are not Ras effector proteins. Additionally, lipids
      can exert a non-competitive type effect, consistent with a protein denaturing
      activity, making difficult extrapolations from in vitro data to the situation
      within cells, and possibly explaining the variability of literature data on
      inhibition by lipids.

PMID- 8576155
TI  - Myristoylation-facilitated binding of the G protein ARF1GDP to membrane
      phospholipids is required for its activation by a soluble nucleotide exchange
      factor.
AB  - We have investigated the role of N-myristoylation in the activation of bovine ADP
      ribosylation factor 1 (ARF1). We previously showed that myristoylation allows
      some spontaneous GDP-to-GTP exchange to occur on ARF1 at physiological Mg2+
      levels in the presence of phospholipid vesicles (Franco, M., Chardin, P., Chabre,
      M., and Paris, S. (1995) J. Biol. Chem. 270, 1337-1341). Here, we report that
      this basal nucleotide exchange can be accelerated (by up to 5-fold) by addition
      of a soluble fraction obtained from bovine retinas. This acceleration is totally
      abolished by brefeldin A (IC50 = 2 microM) and by trypsin treatment of the
      retinal extract, as expected for an ARF-specific guanine nucleotide exchange
      factor. To accelerate GDP release from ARF1, this soluble exchange factor
      absolutely requires myristoylation of ARF1 and the presence of phospholipid
      vesicles. The retinal extract also stimulates guanosine 5'-3-O-(thio)
      triphosphate (GTP gamma S) release from ARF1 in the presence of phospholipids,
      but in this case myristoylation of ARF is not required. These observations,
      together with our previous findings that both myristoylated and non-myristoylated
      forms of ARF GTP-gamma S but only the myristoylated form of ARFGDP bind to
      membrane phospholipids, suggest that (i) the retinal exchange factor acts only on
      membrane-bound ARF, (ii) the myristate is not involved in the protein-protein
      interaction between ARF1 and the exchange factor, and (iii) N-myristoylation
      facilitates both spontaneous and catalyzed GDP-to-GTP exchange on ARF1 simply by
      facilitating the binding of ARFGDP to membrane phospholipids.

PMID- 8576156
TI  - The biosynthetic pathway of the aminonucleoside antibiotic puromycin, as deduced
      from the molecular analysis of the pur cluster of Streptomyces alboniger.
AB  - The pur cluster which encodes the puromycin biosynthetic pathway from
      Streptomyces alboniger was subcloned as a 13-kilobase fragment in plasmid pIJ702
      and expressed in an apparently regulated manner in the heterologous host
      Streptomyces lividans. The sequencing of a 9.1-kilobase DNA fragment completed
      the sequence of pur. This permitted identification of seven new open reading
      frames in the order: napH, pur7, pur10, pur6, pur4, pur5, and pur3. The latter is
      followed by the known pac, dmpM, and pur8 genes. Nine open reading frames are
      transcribed rightward as a unit in opposite direction to that of the pur8 gene
      which is expressed as a monocistronic transcript from the right-most end. napH
      encodes the known N-acetylpuromycin N-acetylhydrolase. The deduced products from
      other open reading frames present similarities to: NTP pyrophosphohydrolases
      (pur7), several oxidoreductases (pur10), the putative LmbC protein of the
      lincomycin biosynthetic pathway from Streptomyces lincolnensis (pur6), S
      adenosylmethionine-dependent methyltransferases (pur5), a variety of presumed
      aminotransferases (pur4), and several monophosphatases (pur3). According to these
      similarities and to previous biochemical work, a puromycin biosynthetic pathway
      has been deduced. No cluster-associated regulatory gene was found. However, both
      pur10 and pur6 genes contain a TTA codon, which suggests that they are
      translationally controlled by the bldA gene product, a specific tRNA(Leu).

PMID- 8576157
TI  - Signal transduction by CD28 costimulatory receptor on T cells. B7-1 and B7-2
      regulation of tyrosine kinase adaptor molecules.
AB  - This study compares the biochemical responses in T cells activated with the CD28
      ligands B7-1 and B7-2. The patterns of tyrosine phosphorylation induced in T
      cells by these two CD28 ligands are identical, but clearly different from the
      tyrosine phosphorylation induced by the T cell receptor (TCR). The TCR regulates
      protein complexes mediated by the adapter Grb2 both in vivo and in vitro. In
      contrast, there is no apparent regulation of in vivo Grb2 complexes in response
      to B7-1 or B7-2. Rather, B7-1 and B7-2 both induce tyrosine phosphorylation of a
      different adaptor protein, p62. The regulation of p62 is a unique CD28 response
      that is not shared with the TCR. These data indicate that B7-1 and B7-2 induce
      identical tyrosine kinase signal transduction pathways. The data show also that
      the TCR and CD28 couple to different adapter proteins, which could explain the
      divergence of TCR and CD28 signal transduction pathways during T cell activation.

PMID- 8576158
TI  - Intermediate filament protein domain interactions as revealed by two-hybrid
      screens.
AB  - All intermediate filament proteins possess three distinct domains: heads, rod and
      tail, and subdomains within the rod called helices 1A, 1B, 2A, and 2B. Subunit
      packing within a filament is a consequence of interactions among these domains.
      Several such interactions are known, but probably many more contribute to
      stabilizing filament structure. We examined a number of such potential
      interactions using the yeast two-hybrid system. Domains or subdomains of murine
      vimentin, a Type III intermediate filament protein, were fused with either the
      DNA-binding or trans-activating domain of GAL4, a transcription factor.
      Interaction between the vimentin domains/subdomains functionally reconstituted
      GAL4, thereby activating transcription of a GAL1-LacZ reporter gene. The
      oligomeric state at which the interactions took place, i.e. whether the
      domains/subdomains were dimeric or tetrameric as they interacted, was also
      determined. These studies revealed a number of interesting interactions, among
      which was a strong homotypic binding to helix 2B to form tetramers. They also
      demonstrated a lack of interaction among others expected to do so based on
      current structural models. From these results we deduced which of the candidates
      for interactions, suggested by current models, were true protein-protein
      interactions and which represented nearest-neighbors only. Thus, the A11 and A22
      modes of molecular alignment identified by Steinert et al. (Steinert, P. M.,
      Marekov, L. N., Fraser, R. D. B., and Parry, D. A. D. (1993) J. Mol. Biol. 230,
      436-452) are probably true interactions, whereas the A12 and ACN modes may
      describe adjacent but non-interacting molecules.

PMID- 8576159
TI  - Proteinase inhibitor 6 cannot be secreted, which suggests it is a new type of
      cellular serpin.
AB  - We have recently described a new serine proteinase inhibitor, proteinase
      inhibitor 6 (PI-6). This serpin has features that suggest it may function
      intracellularly, but its close resemblance to ovalbumin serpins like plasminogen
      activator inhibitor 2 (PAI-2) raises the possibility that it is secreted to
      regulate an extracellular proteinase. To determine whether PI-6 is secreted, we
      have examined its cellular distribution by immunohistochemistry and have
      attempted to induce its release from platelets and from cultured cells. We find
      that PI-6 is present in endothelial and epithelial cells, but it is apparently
      cytoplasmic and it is not released from cells in response to phorbol ester,
      dibutyryl cAMP or tumor necrosis factor alpha treatment. It is also not released
      from activated platelets. The addition of a conventional signal peptide to the
      amino terminus of PI-6 directed its translocation into the endoplasmic reticulum
      (ER), resulting in glycosylation but not secretion of the molecule. By contrast,
      the addition of the same signal peptide to PAI-2 markedly enhanced its
      translocation and secretion. Glycosylated PI-6 was sequestered in the ER and was
      incapable of interacting with thrombin. The failure of PI-6 to move along the
      secretory pathway, and the loss of inhibitory function of ER-localized PI-6,
      demonstrates that unlike PAI-2, PI-6 is not naturally secreted. Taken together,
      these results suggest that PI-6 has evolved to fulfil an intracellular role and
      that it represents a new type of cellular serpin.

PMID- 8576160
TI  - Regulation of amyloid protein precursor (APP) binding to collagen and mapping of
      the binding sites on APP and collagen type I.
AB  - The specific binding of the amyloid precursor protein (APP) to extracellular
      matrix molecules suggests that APP regulates cell interactions and has a function
      as a cell adhesion molecule and/or substrate adhesion molecule. On the molecular
      level APP has binding sites for collagen, laminin, and glycosaminoglycans which
      is a characteristic feature of cell adhesion molecules. We have examined the
      interactions between the APP and collagen types I and IV and identified the
      corresponding binding sites on APP and collagen type I. We show that APP bound
      most efficiently to collagen type I in a concentration-dependent and specific
      manner in the native and heat-denatured states, suggesting an involvement of a
      contiguous binding site on collagen. This binding site was identified on the
      cyanogen bromide fragment alpha 1(I)CB6 of collagen type I, which also binds
      heparin. APP did not bind to collagen type I-heparin complexes, which suggests
      that there are overlapping binding sites for heparin and APP on collagen. We
      localized the site of APP that mediates collagen binding within residues 448-465
      of APP695, which are encoded by the ubiquitously expressed APP exon 12, whereas
      the high affinity heparin binding site of APP is located in exon 9. Since a
      peptide encompassing this region binds to collagen type I and inhibits APP
      collagen type I binding in nanomolar concentrations, this region may comprise the
      major part of the collagen type I binding site of APP. Moreover, our data also
      indicate that the collagen binding site is involved in APP-APP interaction that
      can be modulated by Zn(II) and heparin. Taken together, the data suggest that the
      regulation of APP binding to collagen type I by heparin occurs through the
      competitive binding of heparin and APP to collagen.

PMID- 8576161
TI  - ICE-LAP3, a novel mammalian homologue of the Caenorhabditis elegans cell death
      protein Ced-3 is activated during Fas- and tumor necrosis factor-induced
      apoptosis.
AB  - Members of the ICE/ced-3 gene family have been implicated as components of the
      cell death pathway. Based on similarities with the structural prototype
      interleukin-1 beta-converting enzyme (ICE), family members are synthesized as
      proenzymes that are proteolytically processed to form active heterodimeric
      enzymes. In this report, we describe a novel member of this growing gene family,
      ICE-LAP3, which is closely related to the death effector Yama/CPP32/Apopain. Pro
      ICE-LAP3 is a 35-kDa protein localized to the cytoplasm and expressed in a
      variety of tissues and cell lines. Overexpression of a truncated version of ICE
      LAP3 (missing the pro-domain) induces apoptosis in MCF7 breast carcinoma cells.
      Importantly, upon receipt of a death stimulus, endogenous ICE-LAP3 is processed
      to its subunit forms, suggesting a physiological role in cell death. This is the
      first report to demonstrate processing of a native ICE/ced-3 family member during
      execution of the death program and the first description of the subcellular
      localization of an ICE/ced-3 family member.

PMID- 8576162
TI  - Activation of glutathione transferase P gene by lead requires glutathione
      transferase P enhancer I.
AB  - Glutathione transferase P (GST-P) is specifically induced in rat liver and kidney
      by lead cation. The increase of GST-P mRNA after lead administration is blocked
      by actinomycin D, suggesting that GST-P production by lead is regulated at the
      transcriptional level. To further determine which part of the flanking region of
      the GST-P gene has the lead-responsive cis-element in vivo, we utilized
      transgenic rats with five different constructs having GST-P and/or
      chloramphenicol acetyl-transferase coding sequence. We studied the effect of lead
      on these transgenic rats and on transfected NRK (normal rat kidney) cells and
      found that GST-P induction by lead is indeed regulated at the transcriptional
      level and that the GST-P enhancer I (GPEI) enhancer is an essential cis-element
      required for the activation of the GST-P gene by lead. GPEI consists of two AP-1
      (c-Jun/c-Fos heterodimer) site-like sequences that are palindromically arranged
      and can bind AP-1, c-jun mRNA in the liver increased after lead administration
      and GST-P, and c-Jun had patchy expression in the same hepatocytes 24 h after
      lead exposure. These results suggest that activation of the GST-P gene by lead is
      mediated in major part by enhancer GPEI and that AP-1 may be involved at least
      partially. GPEI has been shown to have essential sequence information for the
      trans-activation of the GST-P gene during chemical hepatocarcinogenesis of the
      rat (Morimura, S., Suzuki, T., Hochi, S., Yuki, A., Nomura, K., Kitagawa, T.,
      Nagatsu, I., Imagawa, M., and Muramatsu, M. (1993) Proc. Natl. Acad. Sci. U.S.A.
      90, 2065-2068; Suzuki, T., Imagawa, M., Hirabayashi, M., Yuki, A., Hisatake, K.,
      Nomura, K., Kitagawa, T., and Muramatsu, M. (1995) Cancer Res. 55, 2651-2655).
      The present study establishes that the same enhancer element does operate in the
      activation of the GST-P gene by lead regardless of the trans-activators involved.

PMID- 8576163
TI  - Mutant and infectious prion proteins display common biochemical properties in
      cultured cells.
AB  - Prion diseases are unusual neurodegenerative disorders that can be both
      infectious and inherited. Both forms are hypothesized to result from a
      posttranslational structural alteration in the cell surface glycoprotein PrPc
      (cellular isoform of the prion protein) that converts it into the protease
      resistant isoform PrPSc (scrapie isoform of the prion protein). However, a direct
      comparison of molecular events underlying these two manifestations of prion
      diseases has not been possible, because there has been no cell culture model for
      the familial forms. We report here that when mutant prion proteins associated
      with three different inherited prion disorders of humans are expressed as their
      murine homologues in cultured Chinese hamster ovary cells, the proteins are
      protease-resistant and detergent-insoluble, two biochemical properties
      characteristic of infectious PrPSc. In addition, each mutant protein remains
      tightly associated with the plasma membrane after enzymatic cleavage of its
      glycosylphosphatidylinositol anchor, a property that we now show is also typical
      of infectious PrPSc. The cell culture system described here is the first in vitro
      model for familial prion diseases and provides compelling evidence that
      infectious and genetic cases share common molecular features.

PMID- 8576164
TI  - Promoter sequences in the RI beta subunit gene of cAMP-dependent protein kinase
      required for transgene expression in mouse brain.
AB  - Neural-specific expression of the mouse regulatory type-I beta (RI beta) subunit
      gene of cAMP-dependent protein kinase is controlled by a fragment of genomic DNA
      comprised of a TATA-less promoter flanked by 1.5 kilobases of 5'-upstream
      sequence and a 1.8-kilobase intron. This DNA contains a complex arrangement of
      transcription factor binding motifs, and previous experiments have shown that
      many of these are recognized by proteins found in brain nuclear extract. To
      identify sequences critical for RI beta expression in functional neurons, we
      performed a deletion analysis in transgenic mice. Evidence is presented that the
      GC-rich proximal promoter is responsible for cell type-specific expression in
      vivo because RI beta DNA containing as little as 17 base pairs (bp) of 5'
      upstream sequence was functional in mouse brain. One likely regulatory element
      coincides with the start of transcription and includes an EGR-1 motif and 3
      consecutive SP1 sites within a 21-bp interval. Maximal RI beta promoter activity
      required the adjacent 663 bp of 5'-upstream DNA where most, but not all, of the
      regulatory activity was localized between position -663 and -333. A 37-bp direct
      repeat lies within this region that contains 2 basic helix-loop-helix binding
      sites, each of which are overlapped by two steroid hormone receptor half-sites,
      and a shared AP1 consensus sequence. Intron I sequences were also tested, and
      deletion of a 388-bp region containing numerous Sp1-like sequences lowered
      transgene activity significantly. These results have identified specific regions
      of the RI beta promoter that are required for the expression of this signal
      transduction protein in mouse neurons.

PMID- 8576165
TI  - Molecular cloning, expression, and localization of E1, an Onchocerca volvulus
      antigen with similarity to brain ankyrin.
AB  - Protective immunity against human onchocerciasis may best be reflected by the
      existence of individuals who in spite of exposure to the filarial nematode
      Onchocerca volvulus do not develop disease (putatively immune). We observed
      preferential recognition of an O. volvulus antigen of approximately 90 kDa by
      sera from putatively immune individuals compared with sera from diseased
      individuals. Screening of an adult worm cDNA library with one serum recognizing
      this antigen almost exclusively led to the identification of a full length clone
      of 2043 base pairs designated E1. The open reading frame of 462 amino acid
      residues shows similarity to human brain ankyrin. E1 appears to represent a small
      transcript of the O. volvulus ankyrin gene. The nonfusion protein obtained by
      expression of the complete E1 cDNA exhibits an apparent molecular mass of 90 kDa
      on SDS-polyacrylamide gel electrophoresis. An antiserum against the recombinant
      protein reacts with the 90-kDa antigen in O. volvulus extract. In O. volvulus, E1
      was localized in the neuronal cell bodies, the nerve ring, and the extracellular
      clefts of the basal labyrinth. These results identify an ankyrin-related O.
      volvulus protein as an immunogen to putatively immune individuals, suggesting
      that neuronal proteins may be important targets for immunity against O. volvulus
      in vivo.

PMID- 8576166
TI  - Glucocorticoid-mediated gene suppression of rat cytokine-induced neutrophil
      chemoattractant CINC/gro, a member of the interleukin-8 family, through
      impairment of NF-kappa B activation.
AB  - The glucocorticoid dexamethasone inhibited the production of the rat cytokine
      induced neutrophil chemoattractant CINC/gro, a counterpart of human melanoma
      growth-stimulating activity that belongs to the interleukin-8 (IL-8) family, in
      the normal rat kidney epithelial cell line NRK-52E stimulated with interleukin-1
      beta (IL-1 beta), lipopolysaccharide, or tumor necrosis factor alpha. The
      accumulation of CINC/gro mRNA induced by these activators was also decreased
      comparably by dexamethasone. A nuclear run-on assay revealed that dexamethasone
      decreased the IL-1 beta-induced transcription of the CINC/gro gene. The half-life
      of CINC/gro mRNA transcripts did not change significantly after exposure to
      dexamethasone, suggesting that this glucocorticoid acts mainly at the
      transcriptional level. Transfection with luciferase expression vectors containing
      5'-deleted and mutated CINC/gro gene sequences demonstrated that the 5'-flanking
      region containing the NF-kappa B binding site is involved in the IL-1 beta- and
      dexamethasone-induced activation and repression of the CINC/gro gene expression,
      respectively. Furthermore, a tandem repeat of the NF-kappa B sequence in the
      CINC/gro gene conferred the inducibility by IL-1 beta and suppression of
      luciferase activity by dexamethasone. In an electrophoretic mobility shift assay,
      dexamethasone diminished the IL-1 beta-induced formation of NF-kappa B complexes,
      which consisted of p65 and p50. Western blotting revealed that dexamethasone
      inhibited the IL-1 beta-induced translocation of p65 from the cytoplasm into the
      nucleus, while the nuclear level of NF-kappa B p50 remained almost unchanged. In
      addition, the degradation of I kappa B-alpha induced by IL-1 beta was not
      inhibited by dexamethasone. These results indicated that the suppression of the
      CINC/gro gene transcription by glucocorticoid occurs through the impairment of NF
      kappa B activation, possibly by interference with the translocation of NF-kappa B
      p65 from the cytoplasm into the nucleus, thereby suppressing transactivation of
      the CINC/gro gene.

PMID- 8576168
TI  - Biochemical and biophysical comparison of native and chemically synthesized
      phospholamban and a monomeric phospholamban analog.
AB  - Phospholamban (PLB) was rapidly isolated from canine cardiac sarcoplasmic
      reticulum using immunoaffinity chromatography and prepared by solid phase peptide
      synthesis. The two proteins are indistinguishable when analyzed by SDS
      polyacrylamide gel electrophoresis and exhibit pentameric oligomeric states. They
      are similarly detected on Western blots, are phosphorylation substrates, have
      identical amino acid compositions that directly reflect their predicted values,
      yield the same internal amino acid sequences upon CNBr digestion, and have
      molecular mass values agreeing with the expected value (approximately 6123 Da).
      Native and synthetic PLB reduced the calcium sensitivity of Ca2+ATPase, which is
      reversed by anti-PLB antibody. A Cys-to-Ser PLB analog, where the cysteines (36,
      41, and 46) were substituted by serines, is monomeric on SDS-polyacrylamide gel
      electrophoresis, can be phosphorylated, and is recognized by polyclonal antisera.
      PLB migrates with a sedimentation coefficient of 4.8 S in sedimentation velocity
      ultracentrifugation experiments, whereas Cys-to-Ser PLB does not sediment,
      consistent with a monomeric state. Circular dichroism spectral analysis of PLB
      indicates about 70% alpha-helical structure, whereas Cys-to-Ser PLB manifests
      only about 30%. Because the physiochemical properties of native and synthetic PLB
      appear identical, the more readily available synthetic protein should be suitable
      for more extensive structural studies.

PMID- 8576167
TI  - A wortmannin-sensitive signal transduction pathway is involved in the stimulation
      of insulin release by vasoactive intestinal polypeptide and pituitary adenylate
      cyclase-activating polypeptide.
AB  - Vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating
      polypeptide-27 (PACAP-27), and PACAP-38 stimulated insulin release with EC50
      values of 0.15, 0.15, and 0.06 nM respectively, as expected for the VIP2/PACAP3
      receptor subtype. Secretion was stimulated promptly and peaked at 6-10 min. At 30
      min, the secretion rate was still 2-3-fold higher than the control rate. The
      peptides increased cyclic AMP and [Ca2+]i transiently so that at 30 min they had
      returned to control values. Therefore, an additional signal is required to
      explain the prolonged stimulation of release. The prolonged effects, but not the
      acute effects of VIP and PACAP on insulin release were inhibited by low
      concentrations of wortmannin, a phosphatidylinositol 3-kinase (PI 3-kinase)
      inhibitor. While wortmannin inhibited PI 3-kinase activity in cell lysates, no
      activation by the peptides was seen. Therefore, the wortmannin-sensitive pathway
      is either dependent on basal PI 3-kinase activity, or another target for
      wortmanin is responsible for inhibition of the peptide-stimulated secretion. It
      is concluded that the acute stimulation of insulin release by VIP and PACAP is
      mediated by increased cyclic AMP and [Ca2+]i, whereas the sustained release is
      mediated by a novel wortmannin-sensitive pathway.

PMID- 8576169
TI  - Synergistic effects of insulin and phorbol ester on mitogen-activated protein
      kinase in Rat-1 HIR cells.
AB  - Regulation of the activity of the extracellular signal regulated kinase (ERK)
      mitogen-activated protein kinases was examined in Rat-1 HIR, a fibroblast cell
      line overexpressing the human insulin receptor. Insulin or phorbol ester induced
      partial activations of ERKs, while a combination of insulin and phorbol ester
      resulted in a synergistic activation. Preincubation with phorbol ester increased
      the subsequent response to insulin. Phorbol ester did not enhance tyrosine
      phosphorylation of the insulin receptor. Insulin did not enhance activation of
      phospholipase D in response to phorbol ester. Lysophosphatidic acid also acted
      synergistically with insulin to induce ERK activation. Lysophosphatidic acid
      alone had little effect on ERK, and did not activate phospholipase D. The
      combination of phorbol ester and insulin maintained tyrosine phosphorylation of
      focal adhesion kinase, while insulin alone decreased its tyrosine
      phosphorylation. Phorbol ester induced phosphorylation of She on
      serine/threonine, while insulin induced tyrosine phosphorylation of She and She
      Grb2 binding. These results suggest that full activation of ERKs in fibroblasts
      can require the cooperation of at least two signaling pathways, one of which may
      result from a protein kinase C-dependent phosphorylation of effectors regulating
      ERK activation. In this manner, phorbol esters may enhance mitogenic signals
      initiated by growth factor receptors.

PMID- 8576170
TI  - Differential expression and phosphorylation of the 74-kDa intermediate chains of
      cytoplasmic dynein in cultured neurons and glia.
AB  - The 74-kDa intermediate chains (IC74) of the cytoplasmic dynein complex are
      believed to be involved in the association of dynein with membranous organelles.
      While each dynein molecule is thought to have two or three IC74 subunits, at
      least six different IC74 protein isoforms were found in dynein from brain.
      Therefore we investigated the relationships of the brain cytoplasmic dynein IC74
      isoforms and their association in the dynein complex at the cellular level. We
      found that cultured cortical neurons and glia express distinct IC74 isoforms. The
      IC74 isoform pattern observed in dynein from cortical neurons was generally
      similar to that found in dynein from adult brain, indicating that there are
      different populations of cytoplasmic dynein in neurons. Two IC74 isoforms were
      observed on two-dimensional gels of dynein from glia, while a single glial IC74
      mRNA was detected. Metabolic labeling of glial dynein with 32P followed by
      treatment of the isolated dynein with phosphatase in vitro demonstrated that one
      of the glial IC74 isoforms is the product of the single glial IC74 mRNA and that
      the other is its phosphoisoform. A single mRNA product and its phosphoisoform are
      therefore sufficient for constitutive dynein function and regulation in glial
      cells.

PMID- 8576171
TI  - ATF3 gene. Genomic organization, promoter, and regulation.
AB  - ATF3 gene, which encodes a member of the activating transcription factor/cAMP
      responsive element binding protein (ATF/CREB) family of transcription factors, is
      induced by many physiological stresses. As a step toward understanding the
      induction mechanisms, we isolated the human ATF3 gene and analyzed its genome
      organization and 5'-flanking region. We found that the human ATF3 mRNA is derived
      from four exons distributed over 15 kilobases. Sequence analysis of the 5'
      flanking region revealed a consensus TATA box and a number of transcription
      factor binding sites including the AP-1, ATF/CRE, NF-kappa B, E2F, and Myc/Max
      binding sites. As another approach to understanding the mechanisms by which the
      ATF3 gene is induced by stress signals, we studied the regulation of the ATF3
      gene in tissue culture cells by anisomycin, an approach that has been used to
      study the stress responses in tissue culture cells. We showed that anisomycin at
      a low concentration activates the ATF3 promoter and stabilizes the ATF3 mRNA.
      Significantly, co-transfection of DNAs expressing ATF2 and c-Jun activates the
      ATF3 promoter. A possible mechanism implicating the C-Jun NH2-terminal
      kinase/stress-activated protein kinase (JNK/SAPK) stress-inducible signaling
      pathway in the induction of the ATF3 gene is discussed.

PMID- 8576172
TI  - The P58 cellular inhibitor complexes with the interferon-induced, double-stranded
      RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and
      activity.
AB  - The 58-kDa protein, referred to as P58, is a cellular inhibitor of the interferon
      induced, double-stranded RNA-activated protein kinase, PKR. The P58 protein
      inhibits both the autophosphorylation of PKR and the phosphorylation of the PKR
      natural substrate, the alpha subunit of eukaryotic initiation factor eIF-2.
      Sequence analysis revealed that P58 is a member of the tetratricopeptide family
      of proteins. Utilizing experimental approaches, which included coprecipitation or
      coselection of native and recombinant wild-type and mutant proteins, we found
      that P58 can efficiently complex with the PKR protein kinase. Attempts to map the
      P58 interactive sites revealed a correlation between the ability of P58 to
      inhibit PKR in vitro and bind to PKR. The DnaJ sequences, present at the carboxyl
      terminus of P58, were dispensable for binding in vitro, while sequences
      containing the eIF-2 alpha similarity region were essential for efficient complex
      formation. Furthermore, not all tetratricopeptide motifs were necessary for PKR
      P58 interactions. Initial experiments to map the binding domains present in PKR
      showed that P58 complexed with PKR molecules that lacked the first RNA binding
      domain but did not bind to a PKR mutant containing only the amino terminus. These
      data, taken together, demonstrate that P58 inhibits PKR through a direct
      interaction, which is likely independent of the binding of double-stranded RNA to
      the protein kinase.

PMID- 8576173
TI  - Characterization of phosphorylation-defective mutants of human P-glycoprotein
      expressed in mammalian cells.
AB  - To assess the role of phosphorylation of the human multidrug resistance MDR1 gene
      product P-glycoprotein for its drug transport activity, phosphorylation sites
      within its linker region were subjected to mutational analysis. We constructed a
      5A mutant, in which serines at positions 661, 667, 671, 675, and 683 were
      replaced by nonphosphorylatable alanine residues, and a 5D mutant carrying
      aspartic acid residues at the respective positions to mimic permanently
      phosphorylated serine residues. Transfection studies revealed that both mutants
      were targeted properly to the cell surface and conferred multidrug resistance by
      diminishing drug accumulation. In contrast to wild-type P-glycoprotein, the
      overexpressed 5A and the 5D mutants exhibited no detectable levels of
      phosphorylation, either in vivo following metabolic labeling of cells with
      [32P]orthophosphate or in vitro in phosphorylation assays with protein kinase C,
      cAMP-dependent protein kinase, or a P-glyco-protein-specific protein kinase
      purified from multidrug-resistant KB-V1 cells. These results reconfirm that the
      major P-glycoprotein phosphorylation sites are located within the linker region.
      Furthermore, the first direct evidence is provided that
      phosphorylation/dephosphorylation mechanisms do not play an essential role in the
      establishment of the multidrug resistance phenotype mediated by human P
      glycoprotein.

PMID- 8576174
TI  - Cathepsin B of Schistosoma mansoni. Purification and activation of the
      recombinant proenzyme secreted by Saccharomyces cerevisiae.
AB  - Procathepsin B from the parasitic trematode Schistosoma mansoni was expressed as
      a glycosylation-minus mutant in yeast cells and purified by means of a histidine
      affinity tag which was added to the carboxyl terminus of the recombinant protein.
      The purified zymogen underwent autoprocessing but required an assisting protease
      for activation. Pepsin-activated schistosomal cathepsin B was further
      characterized with the cathepsin B-specific substrates N-benzyloxycarbonyl (Z)
      Arg-Arg-p-nitroanilide, Z-Arg-Arg-7-amido-4-methyl-coumarin, and Z-Phe-Arg-7
      amido-4-methylcoumarin. A proteolytic activity comparable to mammalian cathepsin
      B was observed. In addition, we analyzed the degradation of human hemoglobin by
      schistosomal cathepsin B, which has been suggested to be the physiological target
      of the protease.

PMID- 8576175
TI  - Expression and biological activity of mouse fibroblast growth factor-9.
AB  - Receptor specificity is an essential mechanism governing the activity of
      fibroblast growth factors (FGF). To begin to understand the developmental role of
      FGF-9/glial activating factor, we have cloned and sequenced the murine FGF-9 cDNA
      and expressed the protein in mammalian cells and in Escherichia coli. We
      demonstrate that the FGF-9 protein is highly conserved between mouse and human.
      Receptor specificity was determined by direct binding to soluble and cell surface
      forms of FGF receptor (FGFR) splice variants and by the mitogenic activity on
      cells, which express unique FGF receptor splice variants. Our data demonstrate
      that FGF-9 efficiently activates the "c" splice forms of FGFR2 and FGFR3,
      receptors expressed in potential target cells for FGF-9. Significantly, FGF-9
      also binds to and activates the "b" splice form of FGFR3, thus becoming the first
      FGF ligand besides FGF-1 to activate this highly specific member of the FGF
      receptor family.

PMID- 8576176
TI  - Activation of glycosylasparaginase. Formation of active N-terminal threonine by
      intramolecular autoproteolysis.
AB  - The activation mechanism of glycosylasparaginase of Flavobacterium
      meningosepticum has been analyzed by site-directed mutagenesis and activation of
      purified precursors in vitro. Mutation of Thr-152 to Ser or Cys leads to gene
      products that are not activated in vivo but are activated in vitro because
      processing of the mutant precursors is inhibited by certain amino acids in the
      cell. Kinetic studies reveal that activation is an intramolecular autoproteolytic
      process. The involvement of His-150 and Thr/Ser/Cys-152 in activation suggests
      that autoproteolysis resembles proteolysis by serine/cysteine proteases. Multiple
      functions of the highly conserved active threonine residue are implicated.

PMID- 8576177
TI  - Functional characterization of the human factor VII 5'-flanking region.
AB  - Factor VII is a vitamin K-dependent coagulation protein essential for proper
      hemostasis. The human Factor VII gene spans 13 kilobase pairs and is located on
      chromosome 13 just 2.8 kilobase pairs 5' to the Factor X gene. In this report, we
      show that Factor VII transcripts are restricted to the liver and that steady
      state levels of mRNA are much lower than those of Factor X. The major
      transcription start site is mapped at -51 by RNase protection assay and primer
      extension experiments. The first 185 base pairs 5' of the translation start site
      are sufficient to confer maximal promoter activity in HepG2 cells. Protein
      binding sites are identified at nucleotides -51 to -32, -63 to -58, -108 to -84,
      and -233 to -215 by DNase I footprint analysis and gel mobility shift assays. A
      liver-enriched transcription factor, hepatocyte nuclear factor-4 (HNF-4), and a
      ubiquitous transcription factor, Spl, are shown to bind within the first 108 base
      pairs of the promoter region at nucleotide sequences ACTTTG and CCCCTCCCCC,
      respectively. The importance of these binding sites in promoter activity is
      demonstrated through independent functional mutagenesis experiments, which show
      dramatically reduced promoter activity. Transactivation studies with an HNF-4
      expression plasmid in HeLa cells also demonstrate the importance of HNF-4 in
      promoting transcription in non-hepatocyte derived cells. Additionally, the
      sequence of a naturally occurring allele containing a previously described
      decanucleotide insert polymorphism at -323 is shown to reduce promoter activity
      by 33% compared with the more common allelic sequence.

PMID- 8576178
TI  - Extracellular domains of the bradykinin B2 receptor involved in ligand binding
      and agonist sensing defined by anti-peptide antibodies.
AB  - Many of the physiological functions of bradykinin are mediated via the B2
      receptor. Little is known about binding sites for bradykinin on the receptor.
      Therefore, antisera against peptides derived from the putative extracellular
      domains of the B2 receptor were raised. The antibodies strongly reacted with
      their corresponding antigens and cross-reacted both with the denatured and the
      native B2 receptor. Affinity-purified antibodies to the various extracellular
      domains were used to probe the contact sites between the receptor and its
      agonist, bradykinin or its antagonist HOE140. Antibodies to extracellular domain
      3 (second loop) efficiently interfered, in a concentration-dependent manner, with
      agonist and antagonist binding and vice versa. Antibodies to extracellular domain
      4 (third loop) blocked binding of the agonist but not of the antagonist, whereas
      antibodies to extracellular domains 1 and 2 or to intracellular domains failed to
      block ligand binding. Antibodies to ectodomain 3 competed with agonistic anti
      idiotypic antibodies for B2 receptor binding. Further, affinity-purified
      antibodies to the amino-terminal portion of extracellular domain 3 transiently
      increased intracellular free Ca2+ concentration and thus are agonists. The Ca2+
      signal was specifically blocked by the B2 antagonist HOE140. By contrast,
      antibodies to the carboxyl-terminal segment of extracellular domain 4 failed to
      trigger Ca2+ release. The specific effects of antibodies to the amino-terminal
      portion of extracellular domain 3 suggest that this portion of the B2 receptor
      may be involved in ligand binding and in agonist function.

PMID- 8576179
TI  - Double-stranded (ds) RNA binding and not dimerization correlates with the
      activation of the dsRNA-dependent protein kinase (PKR).
AB  - Upon binding to double-stranded (ds) RNA, the dsRNA-dependent protein kinase
      (PKR) sequentially undergoes autophosphorylation and activation. Activated PKR
      may exist as a dimer and phosphorylates the eukaryotic translation initiation
      factor 2 alpha subunit (cIF-2 alpha) to inhibit polypeptide chain initiation.
      Transfection of COS-1 cells with a plasmid cDNA expression vector encoding a
      marker gene, activates endogenous PKR, and selectively inhibits translation of
      the marker mRNA, dihydrofolate reductase (DHFR). This system was used to study
      the dsRNA binding and dimerization requirements for over-expressed PKR mutants
      and subdomains to affect DHFR translation. DHFR translation was rescued by
      expression of either an ATP hydrolysis defective mutant PKR K296P, the amino
      terminal 1-243 fragment containing two dsRNA binding motifs, or the isolated
      first RNA binding motif (amino acids 1-123). Mutation of K64E within the dsRNA
      binding motif 1 destroyed dsRNA binding and the ability to rescue DHFR
      translation. Immunoprecipitation of T7 epitope-tagged PKR derivatives from cell
      lysates detected interaction between intact PKR and the amino-terminal 1-243
      fragment as well as a 1-243 fragment harboring the K64E mutation. Expression of
      adenovirus VAI RNA, a potent inhibitor of PKR activity, did not disrupt this
      interaction. In contrast, intact PKR did not interact with fragments containing
      the first dsRNA binding motif (1-123), the second dsRNA binding motif (98-243),
      or the isolated PKR kinase catalytic domain (228-551). These results demonstrate
      that the translational stimulation mediated by the dominant negative PKR mutant
      does not require dimerization, but requires the ability to bind dsRNA and
      indicate these mutants act by competition for binding to activators.

PMID- 8576180
TI  - Expression of the peroxisome proliferator-activated receptor alpha gene is
      stimulated by stress and follows a diurnal rhythm.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors
      that can be activated by fatty acids and peroxisome proliferators. The PPAR alpha
      subtype mediates the pleiotropic effects of these activators in liver and
      regulates several target genes involved in fatty acid catabolism. In primary
      hepatocytes cultured in vitro, the PPAR alpha gene is regulated at the
      transcriptional level by glucocorticoids. We investigated if this hormonal
      regulation also occurs in the whole animal in physiological situations leading to
      increased plasma corticosterone levels in rats. We show here that an
      immobilization stress is a potent and rapid stimulator of PPAR alpha expression
      in liver but not in hippocampus. The injection of the synthetic glucocorticoid
      dexamethasone into adult rats produces a similar increase in PPAR alpha
      expression in liver, whereas the administration of the antiglucocorticoid RU 486
      inhibits the stress-dependent stimulation. We conclude that glucocorticoids are
      major mediators of the stress response. Consistent with this hormonal regulation,
      hepatic PPAR alpha mRNA and protein levels follow a diurnal rhythm, which
      parallels that of circulating corticosterone. To test the effects of variations
      in PPAR alpha expression on PPAR alpha target gene activity, high glucocorticoid
      dependent PPAR alpha expression was mimicked in cultured primary hepatocytes.
      Under these conditions, hormonal stimulation of receptor expression synergizes
      with receptor activation by WY-14,643 to induce the expression of the PPAR alpha
      target gene acyl-CoA oxidase. Together, these results show that regulation of the
      PPAR alpha expression levels efficiently modulates PPAR activator signaling and
      thus may affect downstream metabolic pathways involved in lipid homeostasis.

PMID- 8576181
TI  - Synthesis, processing, and intracellular transport of CD36 during monocytic
      differentiation.
AB  - CD36 is an integral membrane glycoprotein expressed by several cell types,
      including endothelial cells of the microvasculature, erythrocytes, platelets, and
      monocytes. In the monocytic lineage, CD36 is expressed during the late stages of
      differentiation in the bone marrow, in circulating monocytes, and in some tissue
      resident macrophages, and it is thought to mediate the phagocytosis of apoptotic
      cells and the endocytic uptake of modified lipoproteins. Here we analyze the
      synthesis, processing, and intracellular transport of CD36 in U937 and THP-1, two
      human cell lines representing different stages of monocytic maturation. In both
      cell lines, phorbol 12-myristate 13-acetate induces the expression of CD36. A 74
      kDa intracellular precursor is first synthesized that has the hallmarks of a
      resident protein of the endoplasmic reticulum. The precursor protein is later
      processed into a mature form of 90-105 kDa which is transported to the cell
      surface. The kinetics of processing differ significantly in U937 and THP-1. These
      differences are specific for the CD36, as two unrelated proteins (CD11b and
      CD45R) are processed and transported to the surface at similar rates in the two
      cell lines. A 33-kDa endoglycosidase H-sensitive glycoprotein specifically
      associates with the 74-kDa precursor. Coprecipitation of gp33 correlates with
      slow processing of CD36 precursor, suggesting that gp33 may play a role in
      regulating the intracellular transport of CD36, during monocyte maturation.

PMID- 8576182
TI  - Identification, characterization, cloning, and expression of apolipoprotein C-IV,
      a novel sialoglycoprotein of rabbit plasma lipoproteins.
AB  - We have identified and characterized a novel proline- and arginine-rich protein
      component of lipoproteins, present in up to five sialylated isoforms, in rabbit
      blood plasma. The pI of the desialylated protein is 5.7. Based upon its N
      terminal sequence, a complete cDNA sequence of 555 nucleotides was cloned from
      rabbit liver. The synthesized protein is predicted to contain 124 amino acids,
      including a typical signal peptide of 27 residues. The mature protein of 97 amino
      acids, designated apolipoprotein C-IV, is associated with the lipoproteins of
      blood plasma, primarily very low density and high density lipoproteins. It
      contains two potential amphipathic helices characteristic of plasma
      apolipoproteins and forms discoidal micelles with phosphatidylcholine. Northern
      analysis shows a single 0.6-kilobase apolipoprotein C-IV mRNA, detected only in
      the liver, and Southern analysis suggests a single copy gene. Sialylated
      apolipoprotein C-IV is secreted from transfected mammalian cells. Nucleotide
      sequence comparisons demonstrate a strong homology to portions of the upstream
      regions of the mouse and human apolipoprotein C2 genes, within each of which a
      distinct gene has recently been identified. The nucleotide sequences and the
      predicted amino acid sequences, as well as corresponding cDNA sequences in the
      rat and monkey, indicate that the apolipoprotein C4 gene has been highly
      conserved during mammalian evolution.

PMID- 8576183
TI  - Compartmentalization of cholesterol biosynthesis. Conversion of mevalonate to
      farnesyl diphosphate occurs in the peroxisomes.
AB  - We have recently demonstrated that mevalonate kinase and farnesyl diphosphate
      (FPP) synthase are localized predominantly in peroxisomes. This observation
      raises the question regarding the subcellular localization of the enzymes that
      catalyze the individual steps in the pathway between mevalonate kinase and FPP
      synthase (phosphomevalonate kinase, mevalonate diphosphate decarboxylase, and
      isopentenyl diphosphate isomerase). These enzyme are found in the 100,000 x g
      supernatant fraction of cells or tissues and have been considered to be
      cytoplasmic proteins. In the current studies, we show that the activities of
      mevalonate kinase, phosphomevalonate kinase, and mevalonate diphosphate
      decarboxylase are equal in extracts prepared from intact cells and selectively
      permeabilized cells, which lack cytosolic enzymes. We also demonstrate structure
      linked latency of phosphomevalonate kinase and mevalonate diphosphate
      decarboxylase that is consistent with a peroxisomal localization of these
      enzymes. Finally, we show that cholesterol biosynthesis from mevalonate can occur
      in selectively permeabilized cells lacking cytosolic components. These results
      suggest that the peroxisome is the major site of the synthesis of FPP from
      mevalonate, since all of the cholestrogenic enzymes involved in this conversion
      are localized in the peroxisome.

PMID- 8576184
TI  - hMSH2-independent DNA mismatch recognition by human proteins.
AB  - Two distinct mismatch binding activities are detected using bandshift assays with
      human cell extracts and DNA with mispairs at defined positions. One requires
      hMSH2 protein and is absent from extracts of LoVo cells, which contain a partial
      deletion of the hMSH2 gene. The second activity is independent of hMSH2 and is
      present at normal levels in LoVo and three other cell lines, which are defective
      in in vitro hMSH2-dependent binding. The two mismatch recognition activities are
      distinguished by their sensitivity to polycations and can be resolved by
      chromatography on MonoQ. hMSH2-independent activity has been purified extensively
      from wild-type cells and from a cell line deficient in hMSH2-dependent binding.
      The purified material preferentially recognizes A-C, some pyrimidine-pyrimidine
      mismatches, and certain slipped mispaired structures. Binding exhibits some
      sequence preferences. The similar properties of the two mismatch binding
      activities suggest that they both contribute to mismatch repair.

PMID- 8576185
TI  - Cloning of the cDNA for a novel photoreceptor protein.
AB  - A subtractive cDNA cloning strategy was used to isolate a 1381-base pair human
      retina-specific cDNA, human retinal gene 4 (HRG4), which hybridized to a 1.4
      kilobase message in the retina and encoded a 240-amino acid acidic protein with a
      calculated molecular mass of 26,964 Da. The proximal 1/4 of the conceptual
      protein sequence was rich in glycine (18%) and proline (20%), had a predicted
      secondary structure of turns, and showed a loose similarity (19-24%) to various
      alpha-collagen sequences, while the distal 2/4 consisted of a mixture of alpha
      helices, beta-sheets, and turns. Genomic Southern analysis with HRG4 showed cross
      hybridizing sequences in six different species, and HRG4 was 92% homologous with
      a 1264-base pair rat cDNA (rat retinal gene 4; RRG4) at the protein level. The
      region of 100% identity between the two sequences corresponded to the distal 3/4
      of the protein sequence consisting of mixed secondary structures, suggesting a
      functionally important domain. In vitro transcription and translation
      corroborated the open reading frames corresponding to HRG4 and RRG4 in the cDNAs.
      Expression of HRG4 in the retina was localized to the photoreceptors by in situ
      hybridization. Developmentally, RRG4 began to be highly expressed around
      postnatal day 5 in the rat outer retina when the photoreceptors begin to
      differentiate and rapidly increased in expression to reach the mature adult level
      by postnatal day 23. No diurnal fluctuation in expression of RRG4 was seen.

PMID- 8576186
TI  - Triple helix-forming oligonucleotide corresponding to the polypyrimidine sequence
      in the rat alpha 1(I) collagen promoter specifically inhibits factor binding and
      transcription.
AB  - Type I and III fibrillar collagens are the major structural proteins of the
      extracellular matrix found in various organs including the myocardium. Abnormal
      and progressive accumulation of fibrillar type I collagen in the interstitial
      spaces compromises organ function and therefore, the study of transcriptional
      regulation of this gene and specific targeting of its expression is of major
      interest. Transient transfection of adult cardiac fibroblasts indicate that the
      polypurine-polypyrimidine sequence of alpha 1(I) collagen promoter between
      nucleotides - 200 and -140 represents an overall positive regulatory element.
      DNase I footprinting and electrophoretic mobility shift assays suggest that
      multiple factors bind to different elements of this promoter region. We further
      demonstrate that the unique polypyrimidine sequence between -172 and -138 of the
      promoter represents a suitable target for a single-stranded polypurine
      oligonucleotide (TFO) to form a triple helix DNA structure. Modified
      electrophoretic mobility shift assays show that this TFO specifically inhibits
      the protein-DNA interaction within the target region. In vitro transcription
      assays and transient transfection experiments demonstrate that the
      transcriptional activity of the promoter is inhibited by this oligonucleotide. We
      propose that TFOs represent a therapeutic potential to specifically influence the
      expression of alpha 1(I) collagen gene in various disease states where abnormal
      type I collagen accumulation is known to occur.

PMID- 8576187
TI  - Biosynthesis of apolipoprotein B48-containing lipoproteins. Regulation by novel
      post-transcriptional mechanisms.

PMID- 8576188
TI  - Ran binding domains promote the interaction of Ran with p97/beta-karyopherin,
      linking the docking and translocation steps of nuclear import.
AB  - Nuclear protein import is accomplished by two sequential events; docking at the
      nuclear pore complex followed by ATP-dependent translocation across the nuclear
      envelope. Docking of nuclear targeted proteins requires a 56-kDa nuclear
      localization signal receptor (alpha-karyopherin, importin-alpha, SRP1 alpha) and
      a 97-kDa protein (beta-karyopherin, importin-beta). Components necessary for
      translocation include the Ran/TC4 GTPase and NTF2/B-2. The functions of these
      factors at a molecular level remain unclear. We have now found that a complex of
      Ran, in the GTP-bound state, with either the Ran binding protein, RanBP1, or an
      isolated Ran binding domain binds with high affinity and specificity to beta
      karyopherin to form a ternary complex. We find that a C-terminal truncation
      mutant of Ran, delta-DE Ran, also binds to beta-karyopherin and that delta-DE Ran
      can associate with a cytosolic, multiprotein complex that contains beta
      karyopherin and another delta-DE Ran binding protein of 115/120 kDa. These data
      suggest a physical link between docking and translocation mediated by a Ran
      GTPase-Ran binding protein complex.

PMID- 8576189
TI  - Identification and characterization of a gene encoding phospholipase D activity
      in yeast.
AB  - We have identified an open reading frame on chromosome XI of the yeast,
      Saccharomyces cerevisiae, as encoding a protein with phospholipase D (PLD)
      activity. We have named this open reading frame, PLD1, and show that yeast
      bearing a disruption in this gene are unable to catalyze the hydrolysis of
      phosphatidylcholine. PLD1 encodes a hypothetical protein of 1683 amino acids and
      has a predicted molecular mass of 195 kDa. Yeast bearing disruptions at the PLD1
      locus are morphologically normal and grow vegetatively like wild-type cells. In
      contrast, homozygous delta pld1 diploid cells are unable to sporulate and do not
      produce asci under conditions that induce meiosis and sporulation in wild-type
      cells. Thus, PLD1 is likely to be essential for the meiotic cycle in yeast cells.
      This is the first identification of a eukaryotic, nonplant, phosphatidylcholine
      hydrolyzing phospholipase D gene. Because the biological role of PLD is not well
      understood, we expect that delta pld1 yeast will become a useful tool for the
      characterization of PLD functions as well as for the identification of mammalian
      PLD homologs.

PMID- 8576190
TI  - Expression of ob gene in adipose cells. Regulation by insulin.
AB  - The product of the recently cloned mouse obese (ob) gene is likely to play an
      important role in a loop regulating the size of the adipose tissue mass. The
      hormonal regulation of the ob gene could affect adiposity. To investigate this
      point, the effect of insulin on ob gene expression was examined in cells of the
      3T3-F442A preadipocyte clonal line. ob mRNA is absent from exponentially growing,
      undifferentiated cells as well as from confluent preadipose cells. Terminal
      differentiation of preadipose to adipose cells leads to the expression of ob mRNA
      detected by a sensitive and quantitative ribonuclease protection assay. In
      adipose cells, the level of ob mRNA is sensitive to insulin in the nanomolar
      range of concentrations with an increase from an average of 1 copy to 5-10
      copies/cell. The effect of insulin was fully reversible and takes place primarily
      at a transcriptional level. The ob mRNA shows a rapid turnover, with a half-life
      of approximately 2 h in the absence or presence of insulin. The level of secreted
      Ob protein is also regulated by insulin. These results indicate that the ob gene
      is expressed in mature fat cells only and support the possibility that insulin is
      an important regulator of ob gene expression.

PMID- 8576191
TI  - Requirement of transforming growth factor-beta (TGF-beta) type II receptor for
      TGF-beta-induced proliferation and growth inhibition.
AB  - Growth regulation of fibroblasts is important for lung development and repair of
      lung injury. In this study, we investigated the role of transforming growth
      factor-beta (TGF-beta) type II receptor in the TGF-beta-dependent proliferative
      response of lung fibroblasts. TGF-beta stimulated the proliferation of adult lung
      fibroblasts at a low concentration (1 ng/ml), but inhibited the growth of fetal
      lung fibroblasts in a dose-dependent fashion (0.1-10 ng/ml). Cross-linking and
      Northern analysis demonstrated that the two lung fibroblast cell lines expressed
      the TGF-beta type I receptor (T beta RI) and type II receptor (T beta RII). We
      overexpressed in lung fibroblasts a truncated derivative of T beta RII that
      lacked the cytoplasmic serine/threonine kinase domain (T beta RII delta K). T
      beta RII delta K was a dominant-negative inhibitor of TGF-beta signal
      transduction blocking not only TGF-beta-induced mitogenic action upon adult lung
      fibroblasts but also TGF-beta-induced growth inhibition of fetal lung
      fibroblasts. The results indicate that the type II receptor is indispensable for
      mediating both the mitogenic and antiproliferative effects of TGF-beta upon lung
      fibroblasts.

PMID- 8576192
TI  - Adaptor-mediated recruitment of RNA polymerase II to a signal-dependent
      activator.
AB  - The second messenger cAMP stimulates the expression of a number of target genes
      via the protein kinase A-mediated phosphorylation of CREB at Ser-133 (Gonzalez,
      G. A., and Montminy, M. R. (1989) Cell 59, 675-680). Ser-133 phosphorylation
      enhances CREB activity by promoting interaction with a 265-kDa CREB binding
      protein referred to as CBP (Arias, J., Alberts, A., Brindle, P., Claret, F.,
      Smeal, T., Karin, M., Feramisco, J., and Montminy, M. (1994) Nature 370, 226-228;
      Chrivia, J. C., Kwok, R. P., Lamb, N., Hagiwara, M., Montminy, M. R., and
      Goodman, R. H. (1993) Nature 365, 855-859). The mechanism by which CBP in turn
      mediates induction of cAMP-responsive genes is unknown but is thought to involve
      recruitment of basal transcription factors to the promoter. Here we demonstrate
      that CBP associates specifically with RNA polymerase II in HeLa nuclear extracts.
      This association in turn permits RNA polymerase II to be recruited to CREB in a
      phospho-(Ser-133)-dependent manner. As anti-CBP antiserum, which inhibits
      recruitment of CBP and RNA polymerase II to phospho-(Ser-133) CREB, attenuates
      transcriptional induction by protein kinase A in vitro, our results demonstrate
      that the CBP-RNA polymerase II complex is critical for expression of cAMP
      responsive genes.

PMID- 8576193
TI  - Phosphorylation of Bcl-2 protein and association with p21Ras in Ras-induced
      apoptosis.
AB  - p21Ras mediates mitogenic responses and also renders cells susceptible to
      apoptosis after inhibition of protein kinase C (PKC) activity. Ras-induced
      apoptosis can be blocked by the proto-oncogene bcl-2, but the biochemical or
      functional nature of Bcl-2 regulation of Ras-induced apoptosis is not understood.
      We demonstrate that Bcl-2 and p21Ras molecules can be co-immunoprecipitated in
      Jurkat cells. The level of this association is enhanced when an apoptotic
      stimulus (inhibition of PKC activity) is delivered. Bcl-2/p21Ras association is
      coincident with new phosphorylation of the Bcl-2 protein. Inhibition of this
      phosphorylation prevents protection from apoptosis by Bcl-2, providing a
      functional correlation to the phosphorylation event. The Bcl-2/p21Ras association
      cannot be competed by exogenous glutathione S-transferase-Ras fusion protein,
      suggesting that the endogenous complex may be formed before cell lysis. These
      results provide a possible mechanism of regulation of Ras-induced apoptosis by
      Bcl-2.

PMID- 8576194
TI  - 2',5'-Dideoxyadenosine 3'-polyphosphates are potent inhibitors of adenylyl
      cyclases.
AB  - 2',5'-Dideoxyadenosine 3'-di- and triphosphates were tested as inhibitors of
      brain adenylyl cyclases. With an IC50 approximately 40 nM, 2',5'-dideoxy-3'-ATP
      is the most potent nonprotein synthetic regulator of adenylyl cyclases thus far
      described. Neither 2',5'-dideoxy-3'-ADP nor 2',5'-dideoxy-3'-ATP inhibited
      activity by competition with substrate, and the linear noncompetitive inhibition
      observed was consistent with interaction via a distinct domain. The availability
      of this ligand will permit the development of a variety of probes that will be
      extremely useful in investigating adenylyl cyclase structure and the role(s) that
      this class of compound may play in physiologically regulating cell function.

PMID- 8576195
TI  - Membrane asymmetry is maintained during influenza-induced fusion.
AB  - We have investigated the influence of influenza-induced membrane fusion on the
      transverse asymmetry of the viral and target membranes. Large unilamellar
      vesicles containing headgroup-labeled fluorescent phospholipid analogues in both
      leaflets of the membrane were treated with phospholipase D, converting all outer
      membrane phospholipids to phosphatidic acid and leading to the release of the
      fluorescent label from the outside leaflet. After fusion of virus with these
      liposomes, addition of the enzyme to the fusion product did not release
      fluorescent label again, indicating that the phospholipid analogues from the
      inner leaflet of the membranes had not appeared on the outer leaflet. Moreover,
      the integral membrane protein hemagglutinin, which is present on the outer
      leaflet of the viral membrane, was quantitatively digested with protease after
      fusion, indicating that hemagglutinin remained on the outer leaflet of the fusion
      product. Therefore, there is no merger of the inner with outer leaflets of the
      viral or the liposomal membrane during fusion and transverse membrane asymmetry
      is maintained.

PMID- 8576196
TI  - Arrangement of transmembrane domains in adrenergic receptors. Similarity to
      bacteriorhodopsin.
AB  - G protein-coupled receptors (GPCRs) have seven hydrophobic domains, which are
      thought to span the lipid bilayer as alpha helical transmembrane domains (TMDs).
      The tertiary structure of GPCRs has not been determined; however, molecular
      models of GPCRs have generally been based on bacteriorhodopsin, which is
      functionally unrelated to GPCRs but has a similar secondary structure. We sought
      to examine the validity of using bacteriorhodopsin as a scaffold for GPCR model
      building by experimentally determining the orientation of the TMDs of adrenergic
      receptors in the plasma membrane. In separate experiments, three sequential amino
      acid residues (Leu-310, Leu-311, Asn-312) in TMD VII of the beta 2
      adrenoreceptors were mutated to the amino acids found in the homologous domain of
      the alpha 2 adrenoceptor (Phe, Phe, Phe). Exchange of Asn-312 and Leu-311 in the
      beta 2 adrenoceptor resulted in nonfunctional proteins, most likely due to
      incompatibility of the introduced bulky phenylalanine side chain with adjacent
      structural domains in the beta 2 adrenoreceptor. This structural incompatibility
      was "repaired" by replacing the specific beta 2 TMD sequence with an alpha 2
      receptor sequence. TMD I and TMD II complemented the Asn-312-->Phe mutation, and
      TMD III and TMD VI complemented the Leu-311-->Phe mutation. These results
      indicate that TMDs I, II, III, and VI surround TMD VII in a counter-clockwise
      orientation analogous to the orientation of TMDs in bacteriorhodopsin.

PMID- 8576197
TI  - Role of domain II, loop 2 residues of Bacillus thuringiensis CryIAb delta
      endotoxin in reversible and irreversible binding to Manduca sexta and Heliothis
      virescens.
AB  - Site-directed mutagenesis was used to examine the role of domain II, loop 2
      residues, 368RRPFNIGI375, of Bacillus thuringiensis insecticidal protein CryIAb.
      Alanine substitution of residues 368RRP370, called B4, abolished potency toward
      Manduca sexta and Heliothis virescens, and the loss of toxicity was correlated
      directly to substantially reduced binding affinity to brush-border membrane
      vesicles (BBMV) prepared from the target insect midguts. These results indicated
      that these positive charges might be essential to orient the toxin to midgut
      receptor molecule(s). The role of residue Phe371 of CryIAb toxin to M. sexta was
      investigated by substituting a series of residues at this position. Irreversible
      binding and toxicity were affected significantly by hydrophilic, aliphatic, and
      smaller side-chain residues such as Cys, Val, Leu, and Ser but not by Tyr or Trp.
      A hydrophobic aromatic side-chain residue at position 371 was therefore essential
      for irreversible binding of CryIAb toxin in M. sexta. The role of residues
      370PFNIGI375 of CryIAb toxin on H. virescens was also examined. Mutants D2
      (deletion of residues 370-375), G374A (alanine substitution of Gly374), and I375A
      had reduced toxicity to H. virescens. In contrast to our findings with M. sexta,
      the reduction in toxicity of these mutants was correlated directly with loss of
      initial binding to H. virescens BBMV, indicating that these residues perform
      functionally distinct roles in binding and toxicity to different insects. In
      ligand blots, CryIAb recognized a major 210-kDa peptide in M. sexta BBMV and a
      170-kDa peptide in H. virescens BBMV.

PMID- 8576198
TI  - On the acid dissociation constants of bilirubin and biliverdin. pKa values from
      13C NMR spectroscopy.
AB  - Biliverdin and bilirubin are naturally-occurring tetrapyrrolic bile pigments
      containing two propionic acid side chains. These side chains, and their
      propensity for ionization, are critical in the biological disposition of the
      pigments. Surprisingly, accurate dissociation constants for the propionic acid
      groups of biliverdin are unknown, and a wide range of values, extending over some
      4 orders of magnitude, has been suggested for the Ka values of the propionic acid
      groups of bilirubin in aqueous solutions. Recently, pKa values of 6.7-9.3 have
      been reported for bilirubin--values much greater than the value of approximately
      5 typical of propionic acid groups. These curiously high values, currently being
      used to explain the biological transport and metabolism of bilirubin and related
      compounds, have been attributed to intramolecular hydrogen bonding. We have
      determined the pKa values of 99% 13C-enriched (13CO2H) [8(3),12(3)
      13C2]mesobilirubin-XIII, alpha, the corresponding biliverdin, and several
      monopropionic model compounds by 13C NMR spectroscopy. This technique allows
      direct observation and quantitative measurement of the carboxylic acid and
      carboxylate anion carbon signals. Analysis of the variation of carboxyl 13C NMR
      chemical shift with pH gave rubin pKa values of 4.2 and 4.9 and verdin pKa values
      of 3.9 and 5.3 in aqueous buffers containing only a very small quantity (0.086
      mol fraction) of dimethyl sulfoxide. When extrapolated to water, the pKa values
      are essentially unchanged. The data provide the first experimentally-determined
      pKa values for a biliverdin. They indicate that intramolecular hydrogen bonding
      has little effect on the acid dissociation of bilirubin and suggest that the
      equilibrium acidity of the bilirubin carboxylic acid groups is not abnormally
      high but similar to the thermodynamic acidity found in other carboxylic acids, as
      originally suggested by Overbeek et al. (Overbeek, J. T. G., Vink, C. L. J., and
      Deenstra, H. (1955) Recl. Trav. Chim. Pays-Bas 74, 81-84).

PMID- 8576199
TI  - Functional differences in Kv1.5 currents expressed in mammalian cell lines are
      due to the presence of endogenous Kv beta 2.1 subunits.
AB  - The voltage-sensitive currents observed following hKv1.5 alpha subunit expression
      in HEK 293 and mouse L-cells differ in the kinetics and voltage dependence of
      activation and slow inactivation. Molecular cloning, immunopurification, and
      Western blot analysis demonstrated that an endogenous L-cell Kv beta 2.1 subunit
      assembled with transfected hKv 1.5 protein. In contrast, both mRNA and protein
      analysis failed to detect a beta subunit in the HEK 293 cells, suggesting that
      functional differences observed between these two systems are due to endogenous L
      cell Kv beta 2.1 expression. In the absence of Kv beta 2.1, midpoints for
      activation and inactivation of hKv1.5 in HEK 293 cells were -0.2 +/- 2.0 and -9.6
      +/- 1.8 mV, respectively. In the presence of Kv beta 2.1 these values were -14.1
      +/- 1.8 and -22.1 +/- 3.7 mV, respectively. The beta subunit also caused a 1.5
      fold increase in the extent of slow inactivation at 50 mV, thus completely
      reconstituting the L-cell current phenotype in the HEK 293 cells. These results
      indicate that 1) the Kv beta 2.1 subunit can alter Kv1.5 alpha subunit function,
      2) beta subunits are not required for alpha subunit expression, and 3) endogenous
      beta subunits are expressed in heterologous expression systems used to study K+
      channel function.

PMID- 8576200
TI  - Substitutions of glutamate 781 in the Na,K-ATPase alpha subunit demonstrate
      reduced cation selectivity and an increased affinity for ATP.
AB  - The intramembrane Glu781 residue of the Na,K-ATPase alpha subunit has been
      postulated to have a role in the binding and/or occlusion of cations. To
      ascertain the role of Glu781, the residue was substituted with an aspartate,
      alanine, or lysine residue and the mutant Na,K-ATPases were coexpressed with the
      native beta 1 subunit in Sf9 insect cells using the baculovirus expression
      system. All alpha mutants are able to efficiently assemble with the beta 1
      subunit and produce catalytically competent Na,K-ATPase molecules with hydrolytic
      activities comparable to that of the wild-type enzyme. Analysis of the kinetic
      properties of the mutated enzymes showed a decrease in apparent affinity for K+
      compared to wild-type Na,K-ATPase, with the lysine and alanine substitutions
      displaying the greatest reduction. All Na,K-ATPase mutants demonstrated a
      significant increase in apparent affinity for ATP compared to wild-type Na,K
      ATPase, while the sensitivity to the cardiotonic inhibitor, ouabain, was
      unchanged. The dependence on Na+, however, differs among the mutant enzymes with
      both the Glu781-->Asp and Glu781-->Ala mutants displaying a decrease in the
      apparent affinity for the cation, while the Glu781-->Lys mutant exhibits a modest
      increase. Furthermore, in the absence of K+, the Glu781-->Ala mutant displays a
      Na(+)-ATPase activity and a cellular Na+ influx suggesting that Na+ is
      substituting for K+ at the extracellular binding sites. The observation that
      trypsin digestion of the Glu781-->Ala mutant in Na+ medium produces a K(+)
      stabilized tryptic fragment also intimates a decreased capacity of the mutant to
      discriminate between Na+ and K+ at the extracellular loading sites. All together,
      these data implicate Glu781 of the Na,K-ATPase alpha subunit as an important
      coordinate of cation selectivity and activation, although the modest effect of
      Glu781-->Lys substitution seemingly precludes direct involvement of the residue
      in the cation binding process. In addition, the fifth membrane segment is
      proposed to represent an important communicative link between the
      extramembraneous ATP binding domain and the cation transport regions of the Na,K
      ATPase.

PMID- 8576201
TI  - Inhibition of receptor signaling to phospholipase D by Clostridium difficile
      toxin B. Role of Rho proteins.
AB  - Rho proteins have been reported to activate phospholipase D (PLD) in in vitro
      preparations. To examine the role of Rho proteins in receptor signaling to PLD,
      we studied the effect of Clostridium difficile toxin B, which glucosylates Rho
      proteins, on the regulation of PLD activity in human embryonic kidney (HEK) cells
      stably expressing the m3 muscarinic acetylcholine receptor (mAChR). Toxin B
      treatment of HEK cells potently and efficiently blocked mAChR-stimulated PLD. In
      contrast, basal and phorbol ester-stimulated PLD activities were not or only
      slightly reduced. Cytochalasin B and Clostridium botulinum C2 toxin, mimicking
      the effect of toxin B on the actin cytoskeleton but without involving Rho
      proteins, had no effect on mAChR-stimulated PLD. Toxin B did not alter cell
      surface mAChR number and mAChR-stimulated binding of (guanosine 5'-O
      (thio)triphosphate (GTP gamma S) to G proteins. In addition to mAChR-stimulated
      PLD, toxin B treatment also inhibited PLD activation by the direct G protein
      activators, AlF4- and GTP gamma S, studied in intact and permeabilized cells,
      respectively. Finally, C. botulinum C3 exoenzyme, which ADP-ribosylates Rho
      proteins, mimicked the inhibitory effect of toxin B on GTP gamma S-stimulated PLD
      activity. In conclusion, the data presented indicate that toxin B potently and
      selectively interferes with receptor coupling mechanisms to PLD, and furthermore
      suggest an essential role for Rho proteins in receptor signaling to PLD.

PMID- 8576202
TI  - The chromosomal arsR gene of Escherichia coli encodes a trans-acting
      metalloregulatory protein.
AB  - Plasmid-encoded arsenical resistance (ars) operons confer high level resistance
      to arsenicals and antimonials, while the chromosomally encoded ars operon of
      Escherichia coli bestows low level resistance. The transcriptional start site of
      the chromosomal ars mRNA was mapped by primer extension, and putative -10 and -35
      promoter recognition sites were identified. The arsR gene, the first gene in this
      operon, was cloned using polymerase chain reaction. The arsR gene product, the
      ArsR repressor, was expressed and purified. The results of gel mobility shift
      assays indicated that the repressor is a DNA binding protein that binds to a
      fragment of DNA containing the chromosomal ars promoter. The specific binding
      site, as determined by DNase I footprint analysis, spans 33 nucleotides in the
      promoter region, including the putative -35 promoter element. By construction and
      expression of a series of in-frame fusions between truncated arsR genes and the
      coding region for the mature form of beta-lactamase (blaM'), it was shown that
      ArsR is a trans-acting repressor that regulates expression of the chromosomal ars
      operon. In addition, the chromosomally-encoded repressor can regulate expression
      of the ars operon of plasmid R773, and the R773 repressor can cross-regulate
      expression from the chromosomal operon.

PMID- 8576203
TI  - Structural asymmetry of F1-ATPase caused by the gamma subunit generates a high
      affinity nucleotide binding site.
AB  - The alpha 3 beta 3 gamma and alpha 3 beta 3 complexes of F1-ATPase from a
      thermophilic Bacillus PS3 were compared in terms of interaction with
      trinitrophenyl analogs of ATP and ADP (TNP-ATP and TNP-ADP) that differed from
      ATP and ADP and did not destabilize the alpha 3 beta 3 complex. The results of
      equilibrium dialysis show that the alpha 3 beta 3 gamma complex has a high
      affinity nucleotide binding site and several low affinity sites, whereas the
      alpha 3 beta 2 complex has only low affinity sites. This is also supported from
      analysis of spectral change induced by TNP-ADP, which in addition indicates that
      this high affinity site is located on the beta subunit. Single-site hydrolysis of
      substoichiometric amounts of TNP-ATP by the alpha 3 beta 3 gamma complex is
      accelerated by the chase addition of excess ATP, whereas that by the alpha 3 beta
      3 complex is not. We further examined the complexes containing mutant beta
      subunits (Y341L, Y341A, and Y341C). Surprisingly, in spite of very weak affinity
      of the isolated mutant beta subunits to nucleotides (Odaka, M., Kaibara, C.,
      Amano, T., Matsui, T., Muneyuki, E., Ogasawara, K, Yutani, K., and Yoshida, M.
      (1994) J. Biochem. (Tokyo) 115, 789-796), a high affinity TNP-ADP binding site is
      generated on the beta subunit in the mutant alpha 3 beta 3 gamma complexes where
      single-site TNP-ATP hydrolysis can occur. ATP concentrations required for the
      chase acceleration of the mutant complexes are higher than that of the wild-type
      complex. The mutant alpha 3 beta 3 complexes, on the contrary, catalyze single
      site hydrolysis of TNP-ATP rather slowly, and there is no chase acceleration.
      Thus, the gamma subunit is responsible for the generation of a high affinity
      nucleotide binding site on the beta subunit in F1-ATPase where cooperative
      catalysis can proceed.

PMID- 8576204
TI  - Alanine-scanning mutagenesis of a C-terminal ligand binding domain of the insulin
      receptor alpha subunit.
AB  - A recent affinity labeling study has suggested that amino acids 704-717 of the C
      terminus of the insulin receptor represent a contact site for insulin. To
      determine whether these amino acids are part of a ligand binding site, we have
      performed alanine-scanning mutagenesis of this region. Mutant cDNAs encoding
      recombinant secreted receptors were transiently expressed in 293 EBNA cells, and
      their insulin binding properties were evaluated. Of the 14 residues in this
      region only 4 amino acids, Asp-707, Val-712, Pro-716, and Arg-717, could be
      mutated to alanine without compromising insulin binding. The reduction in
      affinity resulting from the individual mutation of the remaining amino acids
      varied from an increase in Kd to 3.69 x 10(-9) M (Asn-711) to greater than 10(-6)
      M (Thr-704, Phe-705, Glu-706, and His-710); the Kd of native secreted recombinant
      receptor is 0.56 x 10(-9) M.

PMID- 8576205
TI  - The roles of integrins and extracellular matrix proteins in the insulin-like
      growth factor I-stimulated chemotaxis of human breast cancer cells.
AB  - The effects of insulin-like growth factor I (IGF-I) on the migration of two human
      breast cancer cell lines, MCF-7 and MDA-231, were examined using a modified
      Boyden chamber. 10 ng/ml was the optimal IGF-I concentration for stimulation of
      migration. The majority of IGF-I-stimulated migration in both cell types was due
      to chemotaxis. MCF-7 cells failed to migrate on membranes coated with gelatin or
      fibronectin and migrated only in small numbers on laminin. In contrast, when
      vitronectin- or type IV collagen-coated membranes were used, the MCF-7 cells
      migrated in large numbers specifically in response to IGF-I but not to 10% fetal
      calf serum, epidermal growth factor, fibroblast growth factor, or platelet
      derived growth factor-BB. An IGF-I receptor-blocking antibody inhibited IGF-I
      stimulated migration in both cell types. In addition, a blocking antibody to the
      alpha v beta 5 integrin (a vitronectin receptor) inhibited migration of MCF-7
      cells in response to IGF-I through vitronectin but not through type IV collagen.
      Similarly, blocking antibodies specific for alpha 2 and beta 1 integrins
      significantly inhibited migration of both cell types through type IV collagen
      coated membranes but not through vitronectin-coated membranes. We conclude that:
      1) IGF-I stimulates migration of these two cell types through the IGF-I receptor;
      2) interaction of vitronectin with the alpha v beta 5 integrin or collagen with
      the alpha 2 beta 1 integrin is necessary for the complete IGF-I response in MCF-7
      cells, and 3) because migration represents an in vitro model for metastatic
      spread, integrins, extracellular matrix proteins, and IGF-I may play coordinated
      roles in the metastasis of breast cancer in vivo.

PMID- 8576206
TI  - A novel human serum lectin with collagen- and fibrinogen-like domains that
      functions as an opsonin.
AB  - Collectins are C-type animal lectins with both collagenous and carbohydrate
      recognition domains and are involved in the first line host defense against
      pathogens. We report here a novel Ca(2+)-dependent and GlcNAc-binding lectin
      consisting of subunits of 35 kDa (P35) with a collagen-like sequence. When P35 is
      isolated from human serum, it forms a homopolymer by means of intermolecular
      disulfide bonding, as is the case with collectins. P35 cDNA was cloned from a
      human liver cDNA library, and the deduced amino acid sequence of 313 residues
      revealed that the mature form of P35 consists mainly of collagen- and fibrinogen
      like domains. The latter contained two potential Ca(2+)-binding sites that may be
      involved in carbohydrate binding. The overall sequence of P35 was highly
      homologous to porcine ficolins alpha and beta. Northern blots of various human
      tissues showed that the major product of the 1.3-kilobase-long P35 transcript is
      expressed in liver. P35 enhanced phagocytosis of Salmonella typhimurium by
      neutrophils, suggesting an opsonic effect via the collagen region. P35 was found
      to bind to GlcNAc-conjugated bovine serum albumin, a neoglycoprotein, as well as
      to neoglycolipids containing complex-type oligosaccharides derived from
      glycoproteins, suggesting that P35 recognizes GlcNAc residues such as those found
      in microbial glycoconjugates and complex-type oligosaccharides. Therefore, P35
      represents a new type of GlcNAc-binding lectin with structural and functional
      similarities to collectins involved in innate immunity.

PMID- 8576207
TI  - The C-terminal extension of yeast seryl-tRNA synthetase affects stability of the
      enzyme and its substrate affinity.
AB  - Saccharomyces cerevisiae seryl-tRNA synthetase (SerRS) contains a 20-amino acid C
      terminal extension, which is not found in prokaryotic SerRS enzymes. A truncated
      yeast SES1 gene, lacking the 60 base pairs that encode this C-terminal domain, is
      able to complement a yeast SES1 null allele strain; thus, the C-terminal
      extension in SerRS is dispensable for the viability of the cell. However, the
      removal of the C-terminal peptide affects both stability of the enzyme and its
      affinity for the substrates. The truncation mutant binds tRNA with 3.6-fold
      higher affinity, while the Km for serine is 4-fold increased relative to the wild
      type SerRS. This indicates the importance of the C-terminal extension in
      maintaining the overall structure of SerRS.

PMID- 8576208
TI  - Identification of the major site of rat prolactin phosphorylation as serine 177.
AB  - Phosphorylation of prolactin by endogenous protein kinases within isolated
      secretory granules was shown to result in the production of both phosphoserine
      and phosphothreonine residues. The majority of the radiolabel was determined to
      be present in the C terminus of the molecule after specific cleavage with
      glandular kallikrein. Glandular kallikrein cleaves in three places at the C
      terminus, liberating three small peptides, only one of which contains a
      phosphorylatable residue. Sequencing of this phosphopeptide showed it to be
      Arg175-Lys185. Thus the major site of prolactin phosphorylation was determined to
      be serine 177. Using a synthetic peptide equivalent to this region of the
      molecule (Ser161-Val180), serine 177 was demonstrated to be a substrate for
      protein kinase A as well as for one of the endogenous granule kinases. Inclusion
      of the synthetic peptide in an endogenous granule phosphorylation reaction
      resulted in competition for the kinase and reduced phosphorylation of prolactin.
      Protein kinase A phosphorylation of purified prolactin resulted in the production
      of only phosphoserine and primarily the most abundant (monophosphorylated)
      variant. We conclude that serine 177 is the major in vivo phosphorylation site of
      rat prolactin and that phosphorylation of this site can be reproduced by protein
      kinase A in vitro. The minor threonine phosphorylation site was demonstrated by
      two-dimensional tryptic peptide mapping and mass analysis to be either threonine
      58 or 63, both of which are contained within a single peptide.

PMID- 8576209
TI  - An effect of voltage on binding of Na+ at the cytoplasmic surface of the Na(+)-K+
      pump.
AB  - This work utilizes proteoliposomes reconstituted with renal Na(+)-K(+)-ATPase to
      study effects of electrical potential (40-80 mV) on activation of pump-mediated
      fluxes of Na+ or Rb+ (K+) ions and on inhibitory effects of Rb+ ions or organic
      cations. The latter include guanidinium derivatives that are competitive Na(+)
      like antagonists (David, P., Mayan, H., Cohen, H., Tal, D. M., and Karlish,
      S.J.D. (1992) J. Biol. Chem. 267, 1141-1149). Cytoplasmic side-positive diffusion
      potentials significantly decreased the K0.5 of Na+ at the cytoplasmic surface for
      activation of ATP-dependent Na(+)-K+ exchange but did not affect the inhibitory
      potency of Rb+ (K+) or any Na(+)-like antagonist. Diffusion potentials did not
      affect activation of Rb(+)-Rb+ exchange by Rb+ ions at the cytoplasmic surface
      and had only a minor effect on Rb+ activation at the extracellular surface.
      Previously, we proposed that the cation binding domain consists of two negatively
      charged sites, to which two K+ or two Na+ ions bind, and one neutral site for the
      third Na+ (Glynn, I. M., and Karlish, S.J.D. (1990) Annu. Rev. Biochem. 59, 171
      205). The present experiments suggest that binding of a Na+ ion in the neutral
      site at the cytoplasmic surface is sensitive to voltage. By contrast, binding of
      Rb+ ions at the extracellular surface of renal pumps appears to be only weakly or
      insignificantly affected by voltage. Inferences on the identity of the charge
      carrying steps, based on experiments using proteoliposomes, are discussed in
      relation to recent evidence that dissociation of Na+ or association of K+ ions,
      at the extracellular surface, represent the major charge-carrying steps.

PMID- 8576210
TI  - A smaller form of the sliding clamp subunit of DNA polymerase III is induced by
      UV irradiation in Escherichia coli.
AB  - The beta subunit of DNA polymerase III holoenzyme of Escherichia coli is a 40.6
      kDa protein that functions as a sliding DNA clamp (Stukenberg, P. T., Studwell
      Vaughan, P. S., and O'Donnell, M. (1991) J. Biol. Chem. 266, 11328-11334). It is
      responsible for tethering the polymerase to DNA and endowing it with the high
      processivity required for DNA replication. Here and in a companion study (Paz
      Elizur, T., Skaliter, R., Blumenstein, S., and Livneh, Z. (1996) J. Biol. Chem.
      271, 2482-2490) we report that the dnaN gene, encoding the beta subunit, contains
      an internal in-frame gene, termed dnaN*, that encodes a smaller form of the beta
      subunit. The novel 26-kDa protein, termed beta*, is UV-inducible, and when
      overexpressed from a plasmid under an inducible promoter, it increases up to 6
      fold the UV resistance of E. coli cells. These findings suggest that the beta*
      protein functions in a reaction associated with DNA repair or recovery of DNA
      replication in UV-irradiated cells.

PMID- 8576211
TI  - Beta*, a UV-inducible smaller form of the beta subunit sliding clamp of DNA
      polymerase III of Escherichia coli. I. Gene expression and regulation.
AB  - The 40.6-kDa beta subunit of DNA polymerase III of Escherichia coli is a sliding
      DNA clamp responsible for tethering the polymerase to DNA and endowing it with
      high processivity (Stukenberg, P. T., Studwell-Vaughan, P. S., and O'Donnell, M.
      (1991) J. Biol. Chem. 266, 11328-11334). UV irradiation of E. coli induces a
      smaller 26-kDa form of the beta subunit, termed beta*, that, when overproduced
      from a plasmid, increases UV resistance of E. coli (Skaliter, R., Paz-Elizur, T.,
      and Livneh, Z. (1996) J. Biol. Chem. 271, 2478-2481). Here we show that this
      protein is synthesized from a UV-inducible internal gene, termed dnaN*, that is
      located in-frame inside the coding region of dnaN, encoding the beta subunit. The
      initiation codon and the Shine-Dalgarno sequence of dnaN* were identified by site
      directed mutagenesis. The dnaN* transcript was shown to be induced upon treatment
      with nalidixic acid, and transcriptional dnaN*-cat gene fusions were UV
      inducible, suggesting induction of dnaN* at the transcriptional level. Analysis
      of translational dnaN*-lacZ gene fusions revealed that UV induction was abolished
      in strains carrying the recA56, lexA3, or delta rpoH mutations, indicating
      involvement of both SOS and heat shock stress responses in the induction process.
      Expression of dnaN* represents a strategy of producing several proteins with
      related functional domains from a single gene.

PMID- 8576212
TI  - Beta*, a UV-inducible shorter form of the beta subunit of DNA polymerase III of
      Escherichia coli. II. Overproduction, purification, and activity as a polymerase
      processivity clamp.
AB  - Control elements located inside the coding sequence of dnaN, the gene encoding
      the beta subunit of DNA polymerase III holoenzyme, direct the synthesis of a
      shorter and UV-inducible form of the beta subunit (Skaliter, R., Paz-Elizur, T.,
      and Livneh, Z. (1996) J. Biol. Chem. 271, 2278-2281, and Paz-Elizur, T.,
      Skaliter, R., Blumenstein, S., and Livneh, Z. (1996) J. Biol. Chem. 271, 2282
      2290). The protein, termed beta*, was overproduced using the phage T7 expression
      system, leading to its accumulation as inclusion bodies at 5-10% of the total
      cellular proteins. beta* was purified in denatured form, followed by refolding to
      yield a preparation > 95% pure. Denatured beta* had a molecular mass of 26 kDa
      and contained two isoforms when analyzed by two-dimensional gel electrophoresis.
      The major isoform had a pI of 5.45, and comigrated with cellular beta*. Size
      exclusion high performance liquid chromatography under nondenaturing conditions
      and chemical cross-linking experiments indicate that beta* is a homotrimer. DNA
      synthesis by DNA polymerase III* was stimulated up to 10-fold by beta*, primarily
      due to an increase in the processivity of polymerization. It is suggested that
      beta* functions as an alternative sliding DNA clamp in a process associated with
      DNA synthesis in UV-irradiated cells.

PMID- 8576213
TI  - Purification and molecular characterization of a novel 16-kDa galectin from the
      nematode Caenorhabditis elegans.
AB  - In our previous study (Hirabayashi, J., Satoh, M., Ohyama, Y., and Kasai, K.
      (1992) J. Biochem. (Tokyo) 111, 553-555), two beta-galactoside-binding lectins
      (apparent subunit molecular masses, 16 and 32 kDa, respectively) were identified
      in the nematode Caenorhabditis elegans. The subsequent study revealed that the 32
      kDa lectin is a member of the galectin family. Since the 32-kDa galectin was
      found to consist of two homologous domains (approximately 16 kDa), 16-kDa lectin
      was thought to be a degradation product of the 32-kDa galectin. To clarify this,
      the 16-kDa lectin was purified by an improved procedure employing extraction with
      a calcium-supplemented buffer. The purified 16-kDa lectin was found to exist as a
      dimer (approximately 30 kDa) and showed hemagglutinating activity toward
      trypsinized rabbit erythrocytes, which was inhibited by lactose. Almost the whole
      sequence of the 16-kDa polypeptide (approximately 95%, 135 amino acids) was
      determined after digestion with various proteases. Based on the obtained
      information, a full-length cDNA was cloned with the aid of RNA-polymerase chain
      reaction. The clone encoded 146 amino acids including initiator methionine
      (calculated molecular mass, 15,928 Da). Based on these results, it was concluded
      that the 16-kDa lectin is a novel member of the galectin family, but not a
      degradation product of the 32-kDa galectin as had previously thought. However,
      the 16-kDa galectin showed relatively low sequence similarities to both the N
      terminal and the C-terminal domains of the 32-kDa galectin (28% and 27%
      identities, respectively) and to various vertebrate galectins (14-27%).
      Nonetheless, all of the critical amino acids involved in carbohydrate binding
      were conserved. These observations suggest that, in spite of phylogenic distance
      between nematodes and vertebrates, both the 16-kDa and 32-kDa nematode isolectins
      have conserved essentially the same function(s) as those of vertebrate galectins,
      probably through recognition of a key disaccharide moiety, "N-acetyllactosamine."

PMID- 8576214
TI  - In situ Ca2+ dependence for activation of Ca2+/calmodulin-dependent protein
      kinase II in vascular smooth muscle cells.
AB  - Activation of Ca2+/calmodulin (CaM)-dependent protein kinase II (CaM kinase II)
      and development of the Ca2+/CaM-independent (autonomous) form of the kinase was
      investigated in cultured vascular smooth muscle (VSM) cells. Within 15 s of
      ionomycin (1 microM) exposure 52.7 +/- 4.4% of the kinase became autonomous, a
      response that was partially maintained for at least 10 min. This correlated with
      32P phosphorylation of CaM kinase II delta-subunits in situ and was abolished by
      pretreatment with the CaM kinase II inhibitor KN-93. The in situ Ca2+ dependence
      for generating autonomous CaM kinase II was determined in cells selectively
      permeabilized to Ca2+ and depleted of sarcoplasmic reticulum Ca2+ by pretreatment
      with thapsigargin. Analysis of the resulting curve revealed an EC50
      (concentration producing 50% of maximal response) of 692 +/- 28 nM [Ca2+]i, a
      maximum of 68 +/- 2% of the total activity becoming autonomous reflecting nearly
      complete activation of CaM kinase II and a Hill slope of 3, indicating a highly
      cooperative process. Based on this dependence and measured [Ca2+]i responses in
      intact cells, increases in autonomous activity stimulated by angiotensin II,
      vasopressin and platelet-derived growth factor-BB (4.6-, 2-, and 1.7-fold,
      respectively) were unexpectedly high. In intact cells stimulated by ionomycin,
      the correlation between autonomous activity and [Ca2+]i resulted in a parallel
      curve with an EC50 of 304 +/- 23 nM [Ca2+]i. This apparent increase in Ca2+
      sensitivity for generating autonomous activity in intact VSM cells was eliminated
      by thapsigargin pretreatment. We conclude that alteration of [Ca2+]i over a
      physiological range activates CaM kinase II in VSM and that this process is
      facilitated by release of Ca2+ from intracellular pools which initiates
      cooperative autophosphorylation and consequent generation of autonomous CaM
      kinase II activity.

PMID- 8576215
TI  - Expression in high yield of pig alpha 1 beta 1 Na,K-ATPase and inactive mutants
      D369N and D807N in Saccharomyces cerevisiae.
AB  - Studies of structure-function relationships in Na,K-ATPase require high yield
      expression of inactive mutations in cells without endogenous Na,K-ATPase
      activity. In this work we developed a host/vector system for expression of fully
      active pig Na,K-ATPase as well as the inactive mutations D369N and D807N at high
      levels in Saccharomyces cerevisiae. The alpha 1- and beta 1-subunit cDNAs were
      inserted into a single 2-microns-based plasmid with a high and regulatable copy
      number and strong galactose-inducible promoters allowing for stoichiometric
      alterations of gene dosage. The protease-deficient host strain was engineered to
      express high levels of GAL4 transactivating protein, thereby causing a 10-fold
      increase in expression to 32,500 +/- 3,000 [3H]ouabain sites/cell. In one
      bioreactor run 150-200 g of yeast were produced with 54 +/- 5 micrograms of Na,K
      pump protein/g of cells. Through purification in membrane bound form the activity
      of the recombinant Na,K-ATPase was increased to 42-50 pmol/mg of protein. The
      Na,K dependence of ATP hydrolysis and the molar activity (4,500-7,000 min-1) were
      close to those of native pig kidney Na,K-ATPase. Mutations to the phosphorylation
      site (D369N) or presumptive cation sites (D807N), both devoid of Na,K-ATPase
      activity, were expressed in the yeast membrane at the same alpha-subunit
      concentration and [3H]ouabain binding capacity as the wild type Na,K-ATPase. The
      high yield and absence of endogenous activity allowed assay of [3H]ATP binding at
      equilibrium, demonstrating a remarkable 18-fold increase in affinity for ATP in
      consequence of reducing the negative charge at the phosphorylation site (D369N).

PMID- 8576216
TI  - Comparative structural and functional features of the human fibrinogen alpha C
      domain and the isolated alpha C fragment. Characterization using monoclonal
      antibodies to defined COOH-terminal A alpha chain regions.
AB  - The alpha C domain of fibrinogen (A alpha-(220-610)) plays a central role in
      maintaining hemostasis by serving as a substrate for factor XIIIa and plasmin.
      Monoclonal antibodies that recognize eight distinct epitopes within the COOH
      terminal two-thirds of the A alpha chain were employed as structural probes to:
      1) isolate the human alpha C domain, 2) compare the topography of the eight
      epitopes within the alpha C domain of intact fibrinogen and in purified alpha C
      fragments, and 3) explore the degree to which the alpha C domain's role as a
      factor XIIIa substrate in intact fibrinogen is preserved within the structure of
      isolated alpha C fragments. Five antibodies were raised against small, synthetic
      peptide immunogens (A alpha-(220-230), A alpha-(425-442), A alpha-(487-498), and
      A alpha-(603-610)), and three were generated against larger cyanogen bromide (A)
      alpha chain derivatives with each epitope subsequently localized to discrete A
      alpha chain sequences (A alpha-(259-276), A alpha-(529-539), and A alpha-(563
      578)). Human alpha C preparations were isolated from mild plasmin digests of
      fibrinogen by successive chromatography on concanavalin A-Sepharose, anti-A alpha
      (425-442)-Sepharose, and Superdex-75 fast protein liquid chromatography.
      Immunochemical characterization indicated that the NH2-terminal residue of alpha
      C fragments was either A alpha-220 or A alpha-231 and that, although the extreme
      COOH-terminal region, A alpha-(603-610), was absent, all molecules were intact at
      least through A alpha-(563-578). Solution phase competitive assays indicated that
      the release of the alpha C domain from intact fibrinogen was associated with
      several conformational changes, e.g. in the vicinity of A alpha-(220-230), A
      alpha-(259-276), A alpha-(487-498), and A alpha-(529-539), but that the relative
      accessibility of other localized structures remained unchanged, e.g. A alpha-(425
      442) and A alpha-(563-578). Immunoblotting analysis of alpha C cross-linking in
      vitro revealed that isolated alpha C fragments could serve as a substrate for
      factor XIIIa. Immunoblotting studies of the A alpha chain proteolysis that occurs
      during thrombolytic therapy indicated that alpha C fragments, similar in size and
      epitope content to those isolated from purified fibrinogen, were released in vivo
      early during fibrinolytic system activation. The collective findings provide new
      information about the fine structure of the fibrinogen alpha C domain and its
      functional implications and also draw attention to the as yet unexplored role of
      alpha C fragments in the pathophysiology of thrombosis and hemostasis.

PMID- 8576217
TI  - Decreased binding of asialoglycoproteins to hepatocytes from ethanol-fed rats.
      Consequence of both impaired synthesis and inactivation of the asialoglycoprotein
      receptor.
AB  - Chronic ethanol administration alters the process of receptor-mediated
      endocytosis in isolated rat hepatocytes. Using the asialoglycoprotein receptor
      (ASGP-R) as a model, we have previously shown decreased binding of
      asialoglycoproteins to this receptor after as early as 1 week of ethanol
      administration. In the present study, we further analyzed the mechanism(s)
      responsible for this impairment by determining the ligand and antibody binding
      characteristics of the ASGP-R in rats fed ethanol over a 5-week time course. The
      results presented here demonstrate that ethanol treatment for 4 days
      significantly impaired total ligand binding without affecting antibody binding.
      Ethanol administration for a longer period of 1-2 weeks resulted in intermediate
      impairments in both ligand and antibody binding. After 5 weeks of ethanol
      exposure, ligand and antibody binding were equally lowered. In contrast to total
      cellular receptor binding, surface binding of both ligand and antibody were
      decreased over the entire time course of ethanol administration. Our data
      indicate that the ASGP-R is initially inactivated during the time course of
      ethanol exposure and that a redistribution of surface receptors to intracellular
      compartments occurs. Northern blot analysis showed that there was a significant
      decrease in receptor mRNA content in the 5-week chronically fed animals but not
      in the animals fed for 1 week. In addition, after 5 weeks of ethanol feeding,
      biosynthetic labeling of the ASGP-R was decreased in the ethanol cells,
      indicating impaired synthesis of the ASGP-R. In summary, an early inactivation of
      the ASGP-R occurs during ethanol exposure followed by an actual decrease in
      protein and mRNA content for the receptor.

PMID- 8576218
TI  - Quantifying the carboxylation of pyruvate in pancreatic islets.
AB  - Pyruvate has been estimated to enter the citric acid cycle in islets by
      carboxylation to the same extent or more than by decarboxylation. Those estimates
      were made assuming the dimethyl esters of [1,4-14C]succinate and [2-3
      14C]succinate, incubated with islets at a concentration of 10 mM, gave the same
      ratio of 14CO2 yields as if [1-14C]acetate and [2-14C]acetate had been incubated.
      The labeled succinates, at 10 mM, but not 1 mM, are now shown to give ratios
      higher than the labeled acetates at those concentrations and therefore higher
      estimates when related to yields from [2-14C]glucose and [6-14C]glucose. Using
      the labeled acetate ratios in paired incubations, the rate of pyruvate
      carboxylation is still estimated to be about two-thirds the rate of pyruvate
      decarboxylation. Participation of the malic enzyme-catalyzed reaction explains
      the greater ratio of yields of 14CO2 from the succinates at 10 mM than 1 mM and
      increases in those ratios on glucose addition and can account for the removal
      from the citric acid cycle of oxaloacetate carbon formed in the carboxylation.

PMID- 8576219
TI  - S100 beta stimulates inducible nitric oxide synthase activity and mRNA levels in
      rat cortical astrocytes.
AB  - The glia-derived, neurotrophic protein S100 beta has been implicated in
      development and maintenance of the nervous system. However, S100 beta has also
      been postulated to play a role in mechanisms of neuropathology, because of its
      specific localization and selective overexpression in Alzheimer's disease. To
      begin to address the question of whether S100 beta can induce potentially toxic
      signaling pathways, we examined the effects of the protein on nitric oxide
      synthase (NOS) activity in cultures of rat cortical astrocytes. S100 beta
      treatment of astrocytes induced a time- and dose-dependent increase in
      accumulation of the NO metabolite, nitrite, in the conditioned medium. The S100
      beta- stimulated nitrite production was blocked by cycloheximide and by the NOS
      inhibitor N-nitro-L-arginine methylester, but not by the inactive D-isomer of the
      inhibitor. Direct measurement of NOS enzymatic activity in cell extracts and
      analysis of NOS mRNA levels showed that the NOS activated by S100 beta addition
      is the calcium-independent, inducible isoform. Furthermore, the specificity of
      the effects of S100 beta on activation of NOS was demonstrated by the inability
      of S100 alpha and calmodulin to induce an increase in nitrite levels. Our data
      indicate that S100 beta can induce a potent activation of inducible NOS in
      astrocytes, an observation that might have relevance to the role of S100 beta in
      neuropathology.

PMID- 8576220
TI  - Mimosine targets serine hydroxymethyltransferase.
AB  - The plant amino acid, mimosine, is an extremely effective inhibitor of DNA
      replication in mammalian cells (Mosca, P. J., Dijkwel, P. A., and Hamlin, J. L.
      (1992) Mol. Cell. Biol. 12, 4375-4383). Mimosine appears to prevent the formation
      of replication forks at early-firing origins when delivered to mammalian cells
      approaching the G1/S boundary, and blocks DNA replication when added to S phase
      cells after a lag of approximately 2.5 h. We have shown previously that
      [3H]mimosine can be specifically photocross-linked both in vivo and in vitro to a
      50-kDa polypeptide (p50) in Chinese hamster ovary (CHO) cells. In the present
      study, six tryptic peptides (58 residues total) from p50 were sequenced by tandem
      mass spectrometry and their sequences were found to be at least 77.5% identical
      and 96.5% similar to sequences in rabbit mitochondrial serine
      hydroxymethyltransferase (mSHMT). This assignment was verified by precipitating
      the [3H]mimosine-p50 complex with a polyclonal antibody to rabbit cSHMT. The 50
      kDa cross-linked product was almost undetectable in a mimosine-resistant CHO cell
      line and in a CHO gly- cell line that lacks mitochondrial, but not cytosolic,
      SHMT activity. The gly- cell line is still sensitive to mimosine, suggesting that
      the drug may inhibit both the mitochondrial and the cytosolic forms. SHMT is
      involved in the penultimate step of thymidylate biosynthesis in mammalian cells
      and, as such, is a potential target for chemotherapy in the treatment of cancer.

PMID- 8576221
TI  - Properties of the periplasmic ModA molybdate-binding protein of Escherichia coli.
AB  - The modABCD operon, located at 17 min on the Escherichia coli chromosome, encodes
      the protein components of a high affinity molybdate uptake system. Sequence
      analysis of the modA gene (GenBank L34009) predicts that it encodes a periplasmic
      binding protein based on the presence of a leader-like sequence at its N
      terminus. To examine the properties of the ModA protein, the modA structural gene
      was overexpressed, and its product was purified. The ModA protein was localized
      to the periplasmic space of the cell, and it was released following a gentle
      osmotic shock. The N-terminal sequence of ModA confirmed that a leader region of
      24 amino acids was removed upon export from the cell. The apparent size of ModA
      is 31.6 kDa as determined by gel sieve chromatography, whereas it is 22.5 kDa
      when examined by SDS-polyacrylamide gel electrophoresis. A ligand-dependent
      protein mobility shift assay was devised using a native polyacrylamide gel
      electrophoresis protocol to examine binding of molybdate and other anions to the
      ModA periplasmic protein. Whereas molybdate and tungstate were bound with high
      affinity (approximately 5 microM), sulfate, chromate, selenate, phosphate, and
      chlorate did not bind even when tested at 2 mM. A UV spectral assay revealed
      apparent Kd values of binding for molybdate and tungstate of 3 and 7 microM,
      respectively. Strains defective in the modA gene were unable to transport
      molybdate unless high levels of the anion were supplied in the medium. Therefore
      the modA gene product is essential for high affinity molybdate uptake by the
      cell. Tungstate interference of molybdate acquisition by the cell is apparently
      due in part to the high affinity of the ModA protein for this anion.

PMID- 8576222
TI  - Only the first and the last hydrophobic segments in the COOH-terminal third of
      Na,K-ATPase alpha subunit initiate and halt, respectively, membrane translocation
      of the newly synthesized polypeptide. Implications for the membrane topology.
AB  - We studied the topogenic properties of five hydrophobic segments (H5-H9) in the
      COOH-terminal third of Na,K-ATPase alpha subunit using in vitro insertion of
      fusion proteins into endoplasmic reticulum membranes. These fusion proteins
      consisted of several different lengths of truncated alpha subunit starting at
      Met729 and a reporter protein, chloramphenicol acetyltransferase, that was linked
      in frame after each hydrophobic segment. We found that membrane insertion of the
      newly synthesized COOH-terminal third was initiated by H5 and terminated by H9,
      indicating that here only H5 and H9 have topogenic function. The other three, H6
      H8, did not have topogenic function in the native context and were translocated
      into the endoplasmic reticulum lumen. These results were in striking contrast to
      the previous models in which four or six hydrophobic segments were proposed to
      cross the membrane. Furthermore, the findings suggest a novel mechanism for
      achieving the final membrane topology of the COOH-terminal third of the alpha
      subunit.

PMID- 8576224
TI  - High complexity in the expression of the B' subunit of protein phosphatase 2A0.
      Evidence for the existence of at least seven novel isoforms.
AB  - Association of the catalytic subunit (C2) with a variety of regulatory subunits
      is believed to modulate the activity and specificity of protein phosphatase 2A
      (PP2A). In this study we report the cloning and expression of a new family of B
      subunit, the B', associated with the PP2A0 form. Polymerase chain reactions and
      cDNA library screening have identified at least seven cDNA isotypes, designated
      alpha, beta 1, beta 2, beta 3, beta 4, gamma, and delta. The different beta
      subtypes appear to be generated by alternative splicing. The deduced amino acid
      sequences of the alpha, beta 2, beta 3, beta 4 and gamma isoforms predict
      molecular weights of 57,600, 56,500, 60,900, 52,500, and 68,000, respectively.
      The proteins are 60-80% identical and differ mostly at their termini. Two of the
      isoforms, B' beta 3 and B' gamma, contain a bipartite nuclear localization signal
      in their COOH terminus. No homology was found with other B- or B- related
      subunits. Northern analyses indicate a tissue-specific expression of the
      isoforms. Expression of B' alpha protein in Escherichia coli generated a
      polypeptide of approximately 53 kDa, similar to the size of the B' subunit
      present in the purified PP2A0. The recombinant protein was recognized by antibody
      raised against native B' and interacted with the dimeric PP2A (A.C2) to generate
      a trimeric phosphatase. The deduced amino acid sequences of the B' isoforms show
      significant homology to mammalian, fungal, and plant nucleotide sequences of
      unknown function present in the data bases. Notably, a high degree of homology
      (55-66%) was found with a yeast gene, RTS1, encoding a multicopy suppressor of a
      rox3 mutant. Our data indicate that at least seven B' subunit isoforms may
      participate in the generation of a large number of PP2A0 holoenzymes that may be
      spatially and/or functionally targeted to different cellular processes.

PMID- 8576225
TI  - Sequence determinants of C-terminal substrate recognition by the Tsp protease.
AB  - Cytochrome b562 is not cleaved by the tail-specific protease Tsp in vitro or in
      the periplasm of Escherichia coli but becomes a good substrate when the C
      terminal sequence WVAAA is added. Following randomization of the final three
      residue positions of this substrate, 54 different mutants with single residue
      substitutions were recovered. The steady-state expression levels of cytochrome
      variants bearing these mutant tails were similar in an E. coli strain deleted for
      the tsp gene but differed markedly in a strain containing Tsp. Wild-type
      cytochrome b562 and seven variants, displaying a range of intracellular
      expression levels, were purified. These proteins were found to have the same Tm
      values in thermal denaturation experiments but to be cleaved by Tsp at rates
      differing by as much as 30-fold. Overall, the rates of Tsp cleavage of these
      proteins in vitro correlate with their rates of cleavage in vivo as determined by
      pulse-chase experiments. These results indicate that the C-terminal sequence of
      the cytochrome-b562 variants is important in determining their proteolytic fate
      in the cell and show that this degradation is mediated predominantly by Tsp.
      There are different selectivity rules at each of the three C-terminal positions.
      The identity of the C-terminal residue of the substrate, where small, uncharged
      residues (Ala, Cys, Ser, Thr, Val) are preferred, is most important in
      determining the rate of substrate cleavage by Tsp. Non-polar residues are also
      preferred at the second and third positions, but larger and more hydrophobic side
      chains are also acceptable at these positions in good substrates.

PMID- 8576223
TI  - Activation of protein phosphatase 1. Formation of a metalloenzyme.
AB  - The recombinant catalytic subunit of protein phosphatase 1 is produced as an
      inactive enzyme which can be activated by Mn2+ (Zhang, Z., Bai, G., Deans
      Zirattu, S., Browner, M. F., and Lee, E. Y. C. (1992) J. Biol. Chem. 267, 1484
      1490). In this report, we have investigated the effects of divalent cations on
      the activity of recombinant catalytic subunit of protein phosphatase 1. Latent
      phosphatase 1 can be activated by Co2+ or Mn2+, whereas other metal ions tested
      including Fe2+, Zn2+, Mg2+, Ca2+, Cu2+, or Ni2+ were not effective or were only
      weakly effective in activating the enzyme. The Mn(2+)-stimulated activity was
      susceptible to inactivation by EDTA; however, the Co(2+)-activated phosphatase
      was stable after dilution and chelation of the Co2+ with excess EDTA. After
      stable activation of phosphatase 1 using 57Co2+, a stoichiometric amount of
      57Co2+ was shown to be tightly bound to phosphatase 1. These findings demonstrate
      for the first time the generation of a stable metalloenzyme form of phosphatase
      1. Fe2+ reversibly deactivated the Co(2+)-stimulated activity, but did not
      displace the bound Co2+. Interestingly, treatment of the enzyme with a
      combination of Fe2+ and Zn2+ (but not the individual metal ions) significantly
      activated phosphatase 1. These results suggest that at least two metal binding
      sites exist on the enzyme and that protein phosphatase 1 may be an iron/zinc
      metalloprotein in vivo.

PMID- 8576226
TI  - Overexpression of muscle glycogen phosphorylase in cultured human muscle fibers
      causes increased glucose consumption and nonoxidative disposal.
AB  - The effect of increased expression of glycogen phosphorylase on glucose
      metabolism in human muscle was examined in primary cultured fibers transduced
      with recombinant adenovirus AdCMV-MGP encoding muscle glycogen phosphorylase.
      Increments of 20-fold in total enzyme activity and of 14-fold of the active form
      of the enzyme were associated with a 30% reduction in basal glycogen levels.
      Total glycogen synthase activity was doubled in AdCMV-MGP-transduced cells even
      though the activity ratio was decreased. Incubation with forskolin, which
      inactivated glycogen synthase and activated glycogen phosphorylase, induced
      greater net glycogenolysis in engineered cells. In unstimulated fibers, lactate
      production was three times higher in AdCMV-MGP fibers as compared with controls,
      despite similar rates of glycogenolysis. In transduced fibers incubated with 2
      deoxyglucose, the level of 2-deoxyglucose 6-phosphate was about 8-fold elevated
      over the control even though hexokinase activity was unmodified in AdCMV-MGP
      fibers. Overexpression of glycogen phosphorylase also led to enhancement of [U
      14C]glucose incorporation into glycogen, lactate, and lipid. Accordingly,
      determination of lipid cell content revealed that engineered cells were
      accumulating lipids. Furthermore, 14CO2 formation from [U-14C]glucose was 1.6
      fold higher, whereas 14CO2 formation from [6-14C]glucose was unmodified, in AdCMV
      MGP fibers. Our data show that in human skeletal muscle cells in culture, the
      increase in glycogen phosphorylase activity is able to up-regulate glycogen
      synthase activity indicating the enhancement of glycogen turnover. We suggest
      that the increase in glycogen phosphorylase and, thereby, in glycogen metabolism,
      is sufficient to enhance glucose uptake in the muscle cell. Glucose taken up by
      engineered muscle cells is essentially disposed of through nonoxidative
      metabolism and converted into lactate and lipid.

PMID- 8576227
TI  - Extension of recombinant human RANTES by the retention of the initiating
      methionine produces a potent antagonist.
AB  - Extension of recombinant human RANTES by a single residue at the amino terminus
      is sufficient to produce a potent and selective antagonist. RANTES is a
      proinflammatory cytokine that promotes cell accumulation and activation in
      chronic inflammatory diseases. When mature RANTES was expressed heterologously in
      Escherichia coli, the amino-terminal initiating methionine was not removed by the
      endogenous amino peptidases. This methionylated protein was fully folded but
      completely inactive in RANTES bioassays of calcium mobilization and chemotaxis of
      the promonocytic cell line THP-1. However, when assayed as an antagonist of both
      RANTES and macrophage inflammatory polypeptide-1 alpha (MIP-1 alpha) in these
      assays, the methionylated RANTES (Met-RANTES) inhibited the actions of both
      chemokines. T cell chemotaxis was similarly inhibited. The antagonistic effect
      was selective since Met-RANTES had no effect on interleukin-8- or monocyte
      chemotractant protein-1-induced responses in these cells. Met-RANTES can compete
      with both [125I]RANTES and [125I]IMP-1 alpha binding to THP-1 cells or to stably
      transfected HEK cells recombinantly expressing their common receptor, CC-CKR-1.
      These data show that the integrity of the amino terminus of RANTES is crucial to
      receptor binding and cellular activation.

PMID- 8576228
TI  - The molecular basis of the differing kinetic behavior of the two low molecular
      mass phosphotyrosine protein phosphatase isoforms.
AB  - The low molecular mass phosphotyrosine protein phosphatase is a cytosolic enzyme
      of 18 kDa. Mammalian species contain a single gene that codifies for two distinct
      isoenzymes; they are produced through alternative splicing and thus differ only
      in the sequence from residue 40 to residue 73. Isoenzymes differ also in
      substrate specificity and in the sensitivity to activity modulators. In our
      study, we mutated a number of residues included in the alternative 40-73 sequence
      by substituting the residues present in the type 2 isoenzyme with those present
      in type 1 and subsequently examined the kinetic properties of the purified
      mutated proteins. The results enabled us to identify the molecular site that
      determines the kinetic characteristics of each isoform; the residue in position
      50 plays the main role in the determination of substrate specificity, while the
      residues in both positions 49 and 50 are involved in the strong activation of the
      type 2 low M(r) phosphotyrosine protein phosphatase isoenzyme by purine compounds
      such as guanosine and cGMP. The sequence 49-50 is included in a loop whose N
      terminus is linked to the beta 2-strand and whose C terminus is linked to the
      alpha 2-helix; this loop is very near the active site pocket. Our findings
      suggest that this loop is involved both in the regulation of the enzyme activity
      and in the determination of the substrate specificity of the two low M(r)
      phosphotyrosine protein phosphatase isoenzymes.

PMID- 8576229
TI  - Mapping the sites of initiation of DNA replication in rat and human rRNA genes.
AB  - To study the organization of DNA replication in mammalian rRNA genes, the sites
      of initiation of DNA synthesis in rat and human rRNA genes were mapped by two
      independent techniques. In rat cells the growth of the nascent DNA chains was
      blocked by Trioxsalen cross-links introduced in vivo. The fraction of
      "restricted" nascent DNA chains labeled in vivo was isolated, and the abundance
      in this fraction of cloned ribosomal DNA sequences was determined by
      hybridization. In the experiments with human cells, the nascent DNA chains were
      allowed to grow unrestricted for a certain period of time and the movement of the
      replication forks along the rRNA genes was followed by hybridization of cloned
      ribosomal DNA sequences to the "unrestricted" nascent DNA fragments fractionated
      according to size. The results show that in both rRNA genes there are two well
      defined regions of initiation of DNA synthesis. The first one is located upstream
      of the transcription units and the second one is located at the 3'-end of the
      coding regions of the ribosomal DNA repeats.

PMID- 8576230
TI  - On the mechanism of fatty acid-induced proton transport by mitochondrial
      uncoupling protein.
AB  - Uncoupling protein mediates electrophoretic transport of protons and anions
      across the inner membrane of brown adipose tissue mitochondria. The mechanism and
      site of proton transport, the mechanism by which fatty acids activate proton
      transport, and the relationship between fatty acids and anion transport are
      unknown. We used fluorescent probes to measure H+ and anion transport in vesicles
      reconstituted with purified uncoupling protein and carried out a comparative
      study of the effects of laurate and its close analogue, undecanesulfonate.
      Undecanesulfonate was transported by uncoupling protein with a Km value similar
      to that observed for laurate as it activated H+ transport. Both laurate and
      undecanesulfonate inhibited Cl- with competitive kinetics. Undecanesulfonate
      inhibited laurate-induced H+ transport with competitive kinetics.
      Undecanesulfonate and laurate differed in two important respects. (i) Laurate
      caused uncoupling protein-mediated H+ transport, whereas undecanesulfonate did
      not. (ii) Lauric acid was rapidly transported across the bilayer by nonionic
      diffusion, whereas undecanesulfonic was not. We infer that the role of uncoupling
      protein in H+ transport is to transport fatty acid anions and that fatty acids
      induce H+ transport because they can diffuse electroneutrally across the
      membrane. According to this hypothesis, uncoupling protein is a pure anion porter
      and does not transport protons; rather it is designed to enable fatty acids to
      behave as cycling protonophores.

PMID- 8576231
TI  - Analysis of abrB mutations, mutant proteins, and why abrB does not utilize a
      perfect consensus in the -35 region of its sigma A promoter.
AB  - The Bacillus subtilis global regulator AbrB is a DNA-binding protein composed of
      six identical monomers of 96 amino acids that shows specificity to the promoter
      regions of its target genes including its own. We have sequenced thirteen
      previously uncharacterized abrB mutations. Four mutant AbrB proteins were
      purified, and their DNA-binding properties and multimeric structures were
      examined. AbrB23 (R25S) had no appreciable DNA binding activity but retained a
      hexameric structure, indicating that Arg25 is important in DNA interactions.
      Three other mutant proteins, AbrB1 (C56Y), AbrB19 (Gln83-->termination codon),
      and AbrB100 (L69P), showed decreased DNA binding and altered multimeric
      interactions. Analysis of the expression and AbrB binding affinities of mutant
      abrB promoters demonstrated that a consensus -35 region is incompatible with
      proper autoregulation of the abrB gene.

PMID- 8576232
TI  - Progesterone inhibits cholesterol biosynthesis in cultured cells. Accumulation of
      cholesterol precursors.
AB  - Cells acquire cholesterol through endogenous synthesis and through receptor
      mediated uptake of cholesterol-rich low density lipoprotein (LDL). Esterification
      of LDL-derived cholesterol is catalyzed by acyl-CoA:cholesterol acyltransferase
      (ACAT) in the endoplasmic reticulum (ER). Progesterone inhibits esterification,
      and, although the mechanism of inhibition is not completely understood, this
      inhibition results from progesterone's ability to inhibit the activity of
      multiple drug resistance (MDR) P-glycoproteins (P. DeBry and J. E. Metherall,
      submitted for publication). In the current manuscript, we demonstrate that
      progesterone inhibits cholesterol biosynthesis resulting in the accumulation of a
      number of sterol precursors. In Chinese hamster ovary (CHO) cells, high
      concentrations (100 microM) of progesterone completely blocked cholesterol
      production, resulting in the accumulation of lanosterol and a lanosterol
      precursor. Lower concentrations (40 microM) of progesterone cause plasma membrane
      accumulation of several sterol products. The majority of these sterols are
      precursors of cholesterol since they were efficiently converted to cholesterol
      upon removal of progesterone from the culture medium. Although very high
      concentrations (> 200 microM) of progesterone killed CHO cells, their growth was
      restored by the addition of cholesterol to the growth medium, indicating that
      progesterone toxicity resulted from cholesterol auxotrophy. The effect of
      progesterone was not unique to CHO cells; progesterone also inhibited cholesterol
      biosynthesis in all human cell lines tested. These observations suggest that a
      common progesterone-sensitive pathway is involved in both cholesterol
      biosynthesis and the processing of LDL-derived cholesterol.

PMID- 8576233
TI  - Role of multidrug resistance P-glycoproteins in cholesterol biosynthesis.
AB  - Multidrug resistance (MDR) P-glycoproteins were first recognized for their
      ability to catalyze ATP-dependent efflux of cytotoxic agents from tumor cells
      when overexpressed. Despite extensive study, little is known about the normal
      substrate(s) and normal cellular function of these proteins. In the accompanying
      manuscript (Metherall, J. E., Waugh, K., and Li, H. (1996) J. Biol. Chem. 271,
      2627-2633), we demonstrate that progesterone inhibits cholesterol biosynthesis,
      causing the accumulation of a number of cholesterol precursors. In the current
      manuscript, we use several criteria to show that the progesterone receptor is not
      involved in this inhibition. Rather, we demonstrate that progesterone inhibits
      cholesterol biosynthesis by interfering with MDR activity. We show that a steroid
      hormone's ability to inhibit cholesterol biosynthesis is correlated with: 1) its
      general hydrophobicity and 2) its ability to inhibit MDR activity. The only
      exception to this finding is beta-estradiol, which is a more potent inhibitor of
      cholesterol biosynthesis than expected based solely on hydrophobicity and MDR
      inhibition. We further demonstrate that nonsteroidal inhibitors of MDR also
      inhibit cholesterol biosynthesis. Since MDR activity is required for
      esterification of LDL-derived cholesterol (P. DeBry and J. E. Metherall,
      submitted for publication), we investigated the relationship between these
      phenomena and show that inhibition of cholesterol esterification does not cause
      inhibition of cholesterol biosynthesis and that inhibition of cholesterol
      biosynthesis does not cause inhibition of cholesterol esterification. We propose
      a model in which MDR is required for transport of sterols from the plasma
      membrane to the endoplasmic reticulum (ER). Inhibiting this transport prevents
      cholesterol esterification and cholesterol biosynthesis by preventing sterol
      substrates from reaching ER-resident enzymes.

PMID- 8576234
TI  - Heat-induced chaperone activity of HSP90.
AB  - The 90-kDa stress protein, HSP90, is a major cytosolic protein ubiquitously
      distributed in all species. Using two substrate proteins, dihydrofolate reductase
      (DHFR) and firefly luciferase, we demonstrate here that HSP90 newly acquires a
      chaperone activity when incubated at temperatures higher than 46 degrees C, which
      is coupled with self-oligomerization of HSP90. While chemically denatured DHFR
      refolds spontaneously upon dilution from denaturant, oligomerized HSP90 bound
      DHFR during the process of refolding and prevented it from renaturation. DHFR was
      released from the complex with HSP90 by incubating with GroEL/ES complexes in an
      ATP-dependent manner and refolded into the native form. alpha-Casein inhibited
      the binding of DHFR to HSP90 and also chased DHFR from the complex with HSP90.
      These results suggest that HSP90 binds substrates to maintain them in a folding
      competent structure. Furthermore, we found that HSP90 prevents luciferase from
      irreversible thermal denaturation and enables it to refold when postincubated
      with reticulocyte lysates. This heat-induced chaperone activity of HSP90
      associated with its oligomerization may have a pivotal role in protection of
      cells from thermal damages.

PMID- 8576235
TI  - Identification of a phosphatidylinositol 4,5-bisphosphate-binding site in chicken
      skeletal muscle alpha-actinin.
AB  - We previously reported that phosphatidylinositol 4,5-bisphosphate (PIP2)
      dramatically increases the gelating activity of smooth muscle alpha-actinin
      (Fukami, K., Furuhashi, K., Inagaki, M., Endo, T., Hatano, S., and Takenawa, T.
      (1992) Nature 359, 150-152) and that the hydrolysis of PIP2 on alpha-actinin by
      tyrosine kinase activation may be important in cytoskeletal reorganization
      (Fukami, K., Endo, T., Imamura, M., and Takenawa, T. (1994) J. Biol. Chem. 269,
      1518-1522). Here we report that a proteolytic fragment with lysylendopeptidase
      comprising amino acids 168-184 (TAPYRNVNIQNFHLSWK) from striated muscle alpha
      actinin contains a PIP2-binding site. A synthetic peptide composed of the 17
      amino acids remarkably inhibited the activities of phospholipase C (PLC)-gamma 1
      and -delta 1. Furthermore, we detected an interaction between PIP2 and a
      bacterially expressed alpha-actinin fragment (amino acids 137-259) by PLC
      inhibition assay. Point mutants in which arginine 172 or lysine 184 of alpha
      actinin were replaced by isoleucine reduced the inhibitory effect on PLC activity
      by nearly half. Direct interactions between PIP2 and the peptide (amino acids 168
      184) or the bacterially expressed protein (amino acids 137-259) were confirmed by
      enzyme-linked immunosorvent assay. We also found this region homologous to the
      sequence of the PIP2-binding site in spectrin and the pleckstrin homology domains
      of PLC-delta 1 and Grb7. Synthetic peptides from the homologous regions in
      spectrin and PLC-delta 1 inhibited PLC activities. These results indicate that
      residues 168-184 comprise a binding site for PIP2 in alpha-actinin and that
      similar sequences found in spectrin and PLC-delta 1 may be involved in the
      interaction with PIP2.

PMID- 8576236
TI  - Characterization of the actin cross-linking properties of the scruin-calmodulin
      complex from the acrosomal process of Limulus sperm.
AB  - During activation of the Limulus sperm acrosomal process, actin filaments undergo
      a change in twist that is linked with the conversion from a coiled to a straight
      scruin-actin bundle. Since scruin had not been purified, its identity as an actin
      binding protein has not been demonstrated. Using HECAMEG (methyl-6-O-(N-heptyl
      carbamoyl)-alpha-D-glucopyranoside) detergent extraction in concert with high
      calcium, we purified native scruin and identified it as an equimolar complex with
      calmodulin. 125I-Calmodulin overlays and calmodulin-Sepharose indicate that
      scruin binds calmodulin in calcium but not in EGTA. Overlay experiments also map
      the calmodulin binding site between the putative N- and C-terminal beta-propeller
      domains within residues 425-446. Immunofluorescence microscopy reveals that
      calmodulin colocalizes with scruin and actin in the coiled bundle. Although
      scruin binds calmodulin, pelleting assays and electron microscopy show that the
      scruin cross-links F-actin into bundles independently of calcium. Based on our
      biochemical and structural studies, we suggest a model to explain how scruin
      controls a change in twist of actin filaments during the acrosome reaction. We
      predict that calcium subtly alters scruin conformation through its calmodulin
      subunit and the conformation change in scruin causes a shift in the relative
      positions of the scruin-bound actin subunits.

PMID- 8576237
TI  - Coinduction of nitric oxide synthase, argininosuccinate synthetase, and
      argininosuccinate lyase in lipopolysaccharide-treated rats. RNA blot, immunoblot,
      and immunohistochemical analyses.
AB  - Nitric oxide (NO) is synthesized from arginine by nitric oxide synthase (NOS),
      and citrulline which is generated can be recycled to arginine by
      argininosuccinate synthetase (AS) and argininosuccinate lyase (AL). Rats were
      injected with bacterial lipopolysaccharide (LPS), and expression of the inducible
      isoform of NOS (iNOS), AS, and AL was analyzed. In RNA blot analysis, iNOS mRNA
      was undetectable before the LPS treatment but was induced by LPS in the lung,
      heart, liver, and spleen, and less strongly in the skeletal muscle and testis. AS
      mRNA was induced in the lung and spleen, and AL mRNA was weakly induced in these
      tissues. AS and AL mRNAs were abundant in the control liver and remained
      unchanged after the treatment. Kinetic studies showed that iNOS mRNA increased
      rapidly in both spleen and lung, reached a maximum 2-5 h after the treatment, and
      decreased thereafter. On the other hand, AS mRNA increased more slowly and
      reached a maximum in 6-12 h (by about 10-fold in the spleen and 2-fold in the
      lung). AL mRNA in the spleen and lung increased slowly and remained high up to 24
      h. In immunoblot analysis, increase of iNOS protein was evident in the lung,
      liver, and spleen, and there was an increase of AS protein in the lung and
      spleen. In immunohistochemical analysis, macrophages in the spleen that were
      negative for iNOS and AS before LPS treatment were strongly positive for both
      iNOS and AS after this treatment. As iNOS, AS, and AL were coinduced in rat
      tissues and cells, citrulline-arginine recycling seems to be important in NO
      synthesis under the conditions of stimulation.

PMID- 8576238
TI  - ATP binding and hydrolysis by the multifunctional protein disulfide isomerase.
AB  - We previously reported the ability of protein disulfide isomerase (PDI) to
      undergo an ATP-dependent autophosphorylation. Our efforts to map the modification
      site have been hindered by the low abundance and instability of the labeling.
      Results are presented in this paper on the nature of phospho-PDI, which appears
      as an intermediate with a half-life of 2.5-8.8 min in an ATPase reaction. ATP
      binds to PDI with high affinity, Kd 9.66 microM, and the kinetic parameters KmATP
      and kcat of the ATPase reaction were measured by using a pyruvate kinase-lactate
      dehydrogenase-coupled assay under various conditions. Strikingly, the ATPase
      reaction is stimulated in the presence of denatured polypeptides, while the
      disulfide oxidization activity of PDI is not affected by ATP. However, PDI is
      known to participate in various unrelated functions in the endoplasmic reticulum,
      and ATP could be involved in the regulation of one of these. The results are
      discussed in light of recent findings on ATP-chaperone relationships.

PMID- 8576239
TI  - RER, an evolutionarily conserved sequence upstream of the rhodopsin gene, has
      enhancer activity.
AB  - Previous transgenic mouse experiments localized the mammalian rhodopsin gene
      promoter to a region just upstream of the mRNA start site, and also suggested the
      existence of a second more distal regulatory region. A highly conserved 100-base
      pair (bp) sequence which is homologous to the red and green opsin locus control
      region is located 1.5-2 kilobases upstream of the rhodopsin gene (depending on
      the species). In order to test the activity of this 100-bp region, transgenic
      mice were generated with bovine rhodopsin promoter/lacZ constructs which differed
      only by the presence or absence of the sequence. Of 11 lines generated, all
      demonstrated photoreceptor-specific expression of the transgene, but the lines
      with the putative regulatory region showed significantly higher expression.
      Additional transgenic lines in which the region was fused to a minimal
      heterologous promoter did not show transgene expression in the retina. Gel
      mobility shift and DNase I footprint assays demonstrated that bovine retinal
      nuclear extracts contain retina-specific as well as ubiquitously expressed
      factors that interact with the putative regulatory region in a sequence-specific
      manner. These results indicate that the 100-bp sequence can indeed function in
      vivo as a rhodopsin enhancer region.

PMID- 8576240
TI  - Structures, alternative splicing, and neurexin binding of multiple neuroligins.
AB  - Neuroligin 1 is a neuronal cell surface protein that binds to a subset of
      neurexins, polymorphic cell surface proteins that are also localized on neurons
      (Ichtchenko, K., Hata, Y., Nguyen, T., Ullrich, B., Missler, M., Moomaw, C., and
      Sudhof, T. C. (1995) Cell 81, 435-443). We now describe two novel neuroligins
      called neuroligins 2 and 3 that are similar in structure and sequence to
      neuroligin 1. All neuroligins contain an N-terminal hydrophobic sequence with the
      characteristics of a cleaved signal peptide followed by a large esterase homology
      domain, a highly conserved single transmembrane region, and a short cytoplasmic
      domain. The three neuroligins are alternatively spliced at the same position and
      are expressed at high levels only in brain. Binding studies demonstrate that all
      three neuroligins bind to beta-neurexins both as native brain proteins and as
      recombinant proteins. Tight binding of the three neuroligins to beta-neurexins is
      observed only for beta-neurexins lacking an insert in splice site 4. Thus,
      neuroligins constitute a multigene family of brain-specific proteins with
      distinct isoforms that may have overlapping functions in mediating recognition
      processes between neurons.

PMID- 8576241
TI  - Determinants of helix-loop-helix dimerization affinity. Random mutational
      analysis of SCL/tal.
AB  - Dimerization represents a key regulatory step in the function of basic helix-loop
      helix transcriptional factors. In many instances tissue-specific basic helix-loop
      helix proteins, such as the hematopoietic factor SCL/tal or the myogenic factor
      MyoD, interact with ubiquitously expressed basic helix-loop-helix proteins, such
      as E2A or E2-2. Such dimerization is necessary for high affinity, sequence
      specific DNA binding. Previous biochemical and structural studies have shown the
      helix-loop-helix region to be necessary and sufficient for this interaction. In
      the present study, we analyzed the relative affinities of various helix-loop
      helix interactions using the yeast two-hybrid system. The relative affinities of
      selected helix-loop-helix species for the partner protein E2-2 were as follows:
      Id2 > MyoD > SCL/tal. Mutants of SCL/tal with increased affinity for E2-2 were
      selected from a library of randomly mutated basic helix-loop-helix domains. The
      amino acid changes in these high affinity versions of SCL/tal introduced residues
      that resembled those in the corresponding positions of the Id proteins and MyoD.
      One of the mutants, SCL 12, also contained mutations in highly conserved residues
      previously thought to be necessary for dimerization. This mutant of SCL
      demonstrated diminished temperature sensitivity in in vitro interaction assays as
      compared with the wild type protein. Computational modeling of helix-loop-helix
      dimers provides an explanation for the increased dimerization affinity of SCL
      mutant 12.

PMID- 8576242
TI  - Baculovirus expression of chicken nonmuscle heavy meromyosin II-B.
      Characterization of alternatively spliced isoforms.
AB  - We have expressed two truncated isoforms of chicken nonmuscle myosin II-B using
      the baculovirus expression system. One of the expressed heavy meromyosins
      (HMMexp) consists of two 150-kDa myosin heavy chains (MHCs), comprising amino
      acids 1-1231 as well as two pairs of 20-kDa and 17-kDa myosin light chains (MLCs)
      in a 1:1:1 molar ratio. The second HMMexp was identical except that it contained
      an insert of 10 amino acids (PESPKPVKHQ) at the 25-50-kDa domain boundary in the
      subfragment-1 region of the MHC. These 10 amino acids include a consensus
      sequence (SPK) for proline-directed kinases. Expressed HMMs were soluble at low
      ionic strength and bound to rabbit skeletal muscle actin in an ATP-dependent
      manner. These properties afforded a rapid purification of milligram quantities of
      expressed protein. Both isoforms were capable of moving actin filaments in an in
      vitro motility assay and manifested a greater than 20-fold activation of actin
      activated MgATPase activity following phosphorylation of the 20-kDa MLC. HMMexp
      with the 10-amino acid insert was phosphorylated by Cdc2, Cdk5, and mitogen
      activated protein kinase in vitro to 0.3-0.4 mol of PO4/mol of MHC. The site
      phosphorylated in the MHC was identified as the serine residue present in the 10
      amino acid insert and its presence was confirmed in bovine brain MHCs.
      Characterization of the baculovirus expressed noninserted and inserted MHC
      isoforms with respect to actin-activated MgATPase activity and ability to
      translocate actin filaments in an in vitro motility assay produced the following
      average values following MLC phosphorylation: noninserted HMMexp, Vmax = 0.28 s
      1, Km = 12.7 microM; translocation rate = 0.077 micron/s; inserted HMMexp, Vmax =
      0.37 s-1, Km = 15.1 microM; translocation rate = 0.092 micron/s.

PMID- 8576243
TI  - A region of the integrin VLA alpha 4 subunit involved in homotypic cell
      aggregation and in fibronectin but not vascular cell adhesion molecule-1 binding.
AB  - The VLA-4 (alpha 4 beta 1) integrin is involved in the adhesion of cells to
      fibronectin and vascular cell adhesion molecule-1 (VCAM-1). In order to study
      alpha 4 structure-function relationships, we have expressed mutated alpha 4
      subunit by transfection into VLA-4-negative K562 cells. Substitutions at alpha 4
      residues Arg89-Asp90, which show the highest surface probability indexes inside
      the N-terminal alpha 4/80 fragment, resulted in a reduction in the reactivity of
      all anti-alpha 4 epitope A monoclonal antibodies (mAbs) tested, compared with the
      reactivity with anti-alpha 4 epitopes B1, B2, and C mAb, both by transfectant
      flow cytometry, and by immunoprecipitation and SDS-polyacrylamide gel
      electrophoresis analysis of transfectant surface-iodinated proteins. In contrast,
      substitutions at nearby residues, Gln101, Pro102, and Ile105 did not affect the
      reactivity of any anti-alpha 4 mAb representing the known alpha 4 epitopes.
      Homotypic cell aggregation triggered by anti-alpha 4 epitope A mAb was prevented
      in the transfectants expressing mutated alpha 4 Arg89-Asp90Asp residues, while
      cell aggregation was fully achieved with either anti-alpha 4 epitope B2 or anti
      beta 1 mAb. Mutations at alpha 4 residues Gln101, Pro102, and Ile108 did not
      affect the homotypic cell aggregation of the transfectants expressing these
      mutations. In addition, the adhesion of mutant Arg89-Asp90 alpha 4 transfectants
      to the connecting segment-1-containing fibronectin-40 (FN-40) fragment of
      fibronectin was diminished compared to wild type alpha 4 transfectants, as well
      as to other mutant alpha 4 transfectants. This adhesion to FN-40 was restored
      when the activating anti-beta 1 TS2/16 mAb was present in the adhesion assays. In
      contrast, adhesion to VCAM-1 was not affected by mutations at Arg89-Asp90, nor at
      Gln101, Pro102, and Ile108 alpha 4 residues. Altogether, these results indicate
      that alpha 4 residues Arg89 and Asp90 are included in a region involved in
      homotypic cell aggregation, as well as in adhesion to FN-40, but not to VCAM-1.

PMID- 8576244
TI  - XpsD, an outer membrane protein required for protein secretion by Xanthomonas
      campestris pv. campestris, forms a multimer.
AB  - XpsD is an outer membrane lipoprotein, required for the secretion of
      extracellular enzymes by Xanthomonas campestris pv. campestris. Our previous
      studies indicated that when the xpsD gene was interrupted by transposon Tn5,
      extracellular enzymes were accumulated in the periplasm (Hu, N.-T., Hung, M.-N.,
      Chiou, S.-J., Tang, F., Chiang, D.-C. Huang, H.-Y. and Wu, C.-Y. (1992) J.
      Bacteriol. 174, 2679-2687). In this study, we constructed a series of
      substitutions and deletion mutant xpsD genes to investigate the roles of NH2- and
      COOH-terminal halves of XpsD in protein secretory function. Among these secretion
      defective xpsD mutations, one group (encoded by pCD105, pYLA, pKdA6, and pKD2)
      caused secretion interference when co-expressed with wild type xpsD, but the
      other (encoded by pMH7, pKdPs, and pKDT) did not. Cross-linking studies and gel
      filtration chromatography analysis indicated that the wild type XpsD protein
      forms a multimer in its native state. Similar gel filtration analysis of xpsD
      mutants revealed positive correlations between multimer formation and secretion
      interfering properties exerted by the mutant XpsD proteins in the parental strain
      XC1701. Those mutant XpsD proteins (encoded by pCD105, pYL4, pKdA6, and pKD2)
      that caused secretion interference formed multimers that are similar to the wild
      type XpsD multimers and those (encoded by pMH7, pKdPs, and pKDT) that did not
      formed smaller ones. Furthermore, gel filtration and anion exchange
      chromatography analyses indicated that the wild type XpsD protein co-fractionated
      with XpsD (delta 29-428) or XpsD (delta 448-650) protein but not with XpsD (delta
      74-303) or XpsD (delta 553-759) protein. We propose that the mutant XpsD (delta
      29-428) protein caused secretion interference primarily by forming mixed
      nonfunctional multimers with the wild type XpsD protein in XC1701 (pCD105),
      whereas the mutant XpsD (delta 74-303) did so by competing for unknown factor(s)
      in XC1701(pYL4).

PMID- 8576245
TI  - Interaction of ethanol with inducers of glucose-regulated stress proteins.
      Ethanol potentiates inducers of grp78 transcription.
AB  - GRP78, a molecular chaperone expressed in the endoplasmic reticulum, is a
      "glucose-regulated protein" induced by stress responses that deplete glucose or
      intracisternal calcium or otherwise disrupt glycoprotein trafficking. Previously
      we showed that chronic ethanol exposure increases the expression of GRP78. To
      further understand the mechanism underlying ethanol regulation of GRP78
      expression, we studied the interaction between ethanol and classical modulators
      of GRP78 expression in NG108-15 neuroblastoma x glioma cells. We found that, in
      addition to increasing basal levels of GRP78 mRNA ("induction"), ethanol produced
      greater than additive increases in the induction of GRP78 mRNA by the "classical"
      GRP inducers A23187, brefeldin A, and thapsigargin ("potentiation"). Both the
      ethanol induction and potentiation responses modulated grp78 gene transcription
      as determined by stable transfection analyses with the rat grp78 promoter.
      Ethanol potentiated the action of all classical inducers of grp78 transcription
      that were studied. In contrast, co-treatment with the classical GRP inducers
      thapsigargin and tunicamycin produced only simple additive increases in grp78
      promoter activity. Transient transfection studies with deletion mutants of the
      rat grp78 promoter showed that cis-acting promoter sequences required for ethanol
      induction differ from those mediating responses to classical GRP inducers.
      Furthermore, linker-scanning mutations of the grp78 promoter suggested that the
      ethanol potentiation response required a cis-acting promoter element different
      from those involved in induction by ethanol or classical inducing agents. While
      the ethanol induction response required 16-24 h to be detectable, ethanol
      potentiation of thapsigargin occurred within 6 h. The potentiation response also
      decayed rapidly after ethanol removal. In addition, the protein kinase A
      inhibitor Rp-cAMPS and protein phosphatase inhibitor okadaic acid both increased
      ethanol potentiation of thapsigargin while Sp-cAMPS, an activator of protein
      kinase A, decreased ethanol potentiation. Taken together, our findings suggest
      two mechanisms by which ethanol regulates grp78 transcription, both differing
      from the action of classical GRP inducers such as thapsigargin. One mechanism
      (potentiation) involves a protein phosphorylation cascade and potentiates the
      action of classical GRP inducers. In contrast, GRP78 induction by ethanol
      involves promoter sequences and a mechanistic pathway separate from that of the
      ethanol potentiation response or classical GRP78 inducers. These studies show
      that ethanol produces a novel and complex regulation of grp78 transcription which
      could be of particular importance during neuronal exposure to GRP-inducing
      stressors as might occur with central nervous system injury.

PMID- 8576246
TI  - Multimerization of Hsp42p, a novel heat shock protein of Saccharomyces
      cerevisiae, is dependent on a conserved carboxyl-terminal sequence.
AB  - Rap1p is a transcriptional regulator of Saccharomyces cerevisiae, which plays
      roles in both transcriptional activation and silencing. To identify proteins
      involved in Rap1p-dependent regulation of transcription, we used the two-hybrid
      system to screen for Rap1p-interacting proteins. Two of the clones isolated from
      this screen encode a truncated protein with homology to small heat shock proteins
      (HSPs). Here we present an analysis of this novel S. cerevisiae HSP, which we
      name Hsp42p. Expression of HSP42 is regulated by a range of stress conditions
      similar to S. cerevisiae HSP26, with which Hsp42p shares most homology. However,
      HSP42 expression is more sensitive to increased salt concentration and to
      starvation and, in contrast to HSP26 is expressed in unstressed cells. Hsp42p
      interacts with itself in the two-hybrid assay. This interaction is dependent on a
      hydrophobic region which is conserved among small HSPs. Using bacterially
      expressed Hsp42p fusion proteins. we demonstrate that this is a direct
      interaction. Fractionation of yeast protein extracts by size demonstrates that
      all of the Hsp42p in these extracts is present in complexes with a molecular mass
      of greater than 200 kDa, suggesting that Hsp42p exists in high molecular mass
      complexes.

PMID- 8576247
TI  - The three human syntrophin genes are expressed in diverse tissues, have distinct
      chromosomal locations, and each bind to dystrophin and its relatives.
AB  - The syntrophins are a biochemically heterogeneous group of 58-kDa intracellular
      membrane-associated dystrophin-binding proteins. We have cloned and characterized
      human acidic (alpha 1-) syntrophin and a second isoform of human basic (beta 2-)
      syntrophin. Comparison of the deduced amino acid structure of the three human
      isoforms of syntrophin (together with the previously reported human beta 1
      syntrophin) demonstrates their overall similarity. The deduced amino acid
      sequences of human alpha 1- and beta 2-syntrophin are nearly identical to their
      homologues in mouse, suggesting a strong functional conservation among the
      individual isoforms, Much like beta 1-syntrophin, human beta 2-syntrophin has
      multiple transcript classes and is expressed widely, although in a distinct
      pattern of relative abundance. In contrast, human alpha 1-syntrophin is most
      abundant in heart and skeletal muscle, and less so in other tissues. Somatic cell
      hybrids and fluorescent in situ hybridization were both used to determine their
      chromosomal locations: beta 2-syntrophin to chromosome 16q22-23 and alpha 1
      syntrophin to chromosome 20q11.2. Finally, we used in vitro translated proteins
      in an immunoprecipitation assay to show that, like beta 1-syntrophin, both beta 2
      and alpha 1-syntrophin interact with peptides encoding the syntrophin-binding
      region of dystrophin, utrophin/dystrophin related protein, and the Torpedo 87K
      protein.

PMID- 8576248
TI  - Transcriptional regulation of the tissue factor gene in human epithelial cells is
      mediated by Sp1 and EGR-1.
AB  - Tissue factor (TF) gene expression is rapidly induced in epithelial cells by
      phorbol 12-myristate 13-acetate and serum. We have shown that this induction is
      mediated by a novel serum response region (SRR) (-111 to +14 bp) within the human
      TF promoter. In this study, we characterized cis-acting genetic elements within
      the SRR that regulated basal and inducible expression of the TF gene in HeLa
      cells. Gel mobility shift assays using oligonucleotides spanning the entire SRR
      identified three 12-base pair (bp) motifs within subregions 1, 2, and 3 that
      bound constitutively expressed Sp1 and inducibly expressed EGR-1. Analysis of
      protein binding to these 12-bp motifs by competition with Sp1 and EGR-1 sites,
      mutation, and antibody supershift experiments indicated that they each contained
      distinct EGR-1 and Sp1 sites that overlapped by 6 bp. Functional studies using
      HeLa cells transfected with plasmids containing the wild-type TF promoter (-111
      to +14 bp) or derivatives containing mutations in the three Sp1 and/or EGR-1
      sites examined basal and inducible expression. The Sp1 sites mediated basal
      promoter activity, and both Sp1 and EGR-1 sites were required for maximal
      induction of the TF promoter by phorbol 12-myristate 13-acetate or serum. These
      data indicated that TF gene expression in HeLa cells was regulated by both Sp1
      and EGR-1.

PMID- 8576249
TI  - Functional expression of gastric H+,K(+)-ATPase and site-directed mutagenesis of
      the putative cation binding site and catalytic center.
AB  - Gastric H+,K(+)-ATPase was functionally expressed in the human kidney HEK293 cell
      line. The expressed enzyme catalyzed ouabain-resistant K(+)-dependent ATP
      hydrolysis. The K(+)-ATPase activity was inhibited by SCH 28090, a specific
      inhibitor of gastric proton pump, in a dose-dependent manner. By using this
      functional expression system in combination with site-directed mutagenesis, we
      investigated effects of mutations in the putative cation binding site and the
      catalytic center of the gastric H+,K(+)-ATPase. In Na+,K(+)-ATPase, the glutamic
      acid residue in the 4th transmembrane segment is regarded as one of the residues
      responsible for the K(+)-induced conformational change (Kuntzweiler, T. A.,
      Wallick, E. T., Johnson, C. L., and Lingrel, J. B. (1995) J. Biol. Chem. 270,
      2993-3000). When the corresponding glutamic acid (Glu-345) of H+,K(+)-ATPase was
      mutated to aspartic acid, lysine, or valine, the SCH 28080-sensitive K(+)-ATPase
      activity was abolished. However, when this residue was replaced by glutamine,
      about 50% of the activity was retained. This mutant showed a 10-fold lower
      affinity for K+ (Km = 2.6 mM) compared with the wild-type enzyme (Km = 0.24 mm).
      Thus, Glu-345 is important in determining the K+ affinity of H+,K(+)-ATPase. When
      the aspartic acid residue in the phosphorylation site was mutated to glutamic
      acid, this mutant showed no SCH 28080-sensitive K(+)-ATPase activity. Thus, amino
      acid replacement of the phosphorylation site is not tolerated and a stringent
      structure appears to be required for enzyme activity. When the lysine residue in
      the fluorescein isothiocyanate binding site (part of ATP binding site) was
      mutated to arginine, asparagine, or glutamic acid, the SCH 28080-sensitive K(+)
      ATPase activity was eliminated. However, the mutant in which this residue was
      changed to glutamine had about 30% of the activity, suggesting that amino acid
      replacement of this site is tolerated to a certain extent.

PMID- 8576250
TI  - Post-transcriptional regulation of vascular endothelial growth factor by hypoxia.
AB  - The major control point for the hypoxic induction of the vascular endothelial
      growth factor (VEGF) gene is the regulation of the steady-state level of the
      mRNA. We previously demonstrated a discrepancy between the transcription rate and
      the steady-state mRNA level induced by hypoxia. This led us to examine the post
      transcriptional regulation of VEGF expression. Actinomycin D experiments revealed
      that hypoxia increased VEGF mRNA half-life from 43 +/- 6 min to 106 +/- 9 min.
      Using an in vitro mRNA degradation assay, the half-life of VEGF mRNA 3'
      untranslated region (UTR) transcripts were also found to be increased when
      incubated with hypoxic versus normoxic extracts. Both cis-regulatory elements
      involved in VEGF mRNA degradation under normoxic conditions and in increased
      stabilization under hypoxic conditions were mapped using this degradation assay.
      A hypoxia-induced protein(s) was found that bound to the sequences in the VEGF 3'
      UTR which mediated increased stability in the degradation assay. Furthermore,
      genistein, a tyrosine kinase inhibitor, blocked the hypoxia-induced stabilization
      of VEGF 3'-UTR transcripts and inhibited hypoxia-induced protein binding to the
      VEGF 3'-UTR. These findings demonstrate a significant post-transcriptional
      component to the regulation of VEGF.

PMID- 8576251
TI  - Calcium-dependent stabilization of type I plasminogen activator inhibitor within
      platelet alpha-granules.
AB  - Type 1 plasminogen activator inhibitor (PAI-1) is known to be synthesized in an
      active conformation but it is rapidly converted into an inactive conformation
      (t1/2 1 h) upon incubation at 37 degrees C. This study was initiated to
      investigate the mechanism that account for the presence of active PAI-1 in
      anucleated platelets that have a mean life span of 9-12 days in the circulation.
      Stabilization experiments with a functional immunoassay indicated that the
      activity of PAI-1 in both platelets and in isolated alpha-granules was prolonged
      in comparison to the rapid inactivation of this molecule in their lysates (t1/2 1
      h). Although combined ligand blot/immunoblot analysis revealed that vitronectin
      was the major PAI-1 binding protein in platelets, vitronectin/PAI-1 complexes
      were not detected in alpha-granules using a two-site immunoassay. Co-incubation
      of alpha-granules with a number of agents that disrupt pH gradients (e.g.
      ionophores) had no effect on the stability of PAI-1 activity, whereas incubation
      of alpha-granules with the calcium ionophore A23187 reduced the half-life of PAI
      1 to the levels observed for PAI-1 in solution. Addition of calcium ions to
      intact alpha-granules was an effective means of neutralizing the ionophore's
      effect on PAI-1 activity. Fractionation of alpha-granule proteins on molecular
      sieving columns using conditions known to be present within storage granules
      (e.g. a high calcium concentration) revealed the presence of PAI-1 in fractions
      with a molecular mass of > 10(6) daltons. Immunoabsorption of PAI-1 from these
      column fractions followed by negative staining revealed 25-nm diameter complexes
      of alpha-granule proteins under the electron microscope. PAI-1 activity
      associated with these complexes was prolonged in the presence of calcium ions and
      these high Mr complexes were shown to be composed of a defined set of proteins
      that can be dissociated from PAI-1 by chelation of calcium ions. These data
      indicate that PAI-1 is stabilized by its packaging with other alpha-granule
      proteins in a calcium-dependent manner.

PMID- 8576252
TI  - DNA binding and dimerization of the Fe-S-containing FNR protein from Escherichia
      coli are regulated by oxygen.
AB  - The transcription factor FNR from Escherichia coli regulates transcription of
      genes in response to oxygen deprivation. To determine how the activity of FNR is
      regulated by oxygen, a form of FNR had to be isolated that had properties similar
      to those observed in vivo. This was accomplished by purification of an FNR
      fraction which exhibited enhanced DNA binding in the absence of oxygen. Iron and
      sulfide analyses of this FNR fraction indicated the presence of an Fe-S cluster.
      To determine the type of Fe-S cluster present, an oxygen-stable mutant protein
      LH28-DA154 was also analyzed since FNR LH28-DA154 purified anoxically contained
      almost 3-fold more iron and sulfide than the wild-type protein. Based on the
      sulfide analysis, the stoichiometry (3.3 mol of S2-/FNR monomer) was consistent
      with either one [4Fe-4S] or two [2Fe-2S] clusters per mutant FNR monomer.
      However, since FNR has only four Cys residues as potential cluster ligands and an
      EPR signal typical of a 3Fe-4S cluster was detected on oxidation, we conclude
      that there is one [4Fe-4S] cluster present per monomer of FNR LH28-DA154. We
      assume that the wild type also contains one [4Fe-4S] cluster per monomer and that
      the lower amounts of iron and sulfide observed per monomer were due to partial
      occupancy. Consistent with this, the Fe-S cluster in the wild-type protein was
      found to be extremely oxygen-labile. In addition, molecular-sieve chromatographic
      analysis showed that the majority of the anoxically purified protein was a dimer
      as compared to aerobically purified FNR which is a monomer. The loss of the Fe-S
      cluster by exposure to oxygen was associated with a conversion to the monomeric
      form and decreased DNA binding. Taken together, these observations suggest that
      oxygen regulates the activity of wild-type FNR through the lability of the Fe-S
      cluster to oxygen.

PMID- 8576253
TI  - Identification of important regions in the cytoplasmic juxtamembrane domain of
      type I receptor that separate signaling pathways of transforming growth factor
      beta.
AB  - Proteins in the transforming growth factor-beta (TGF-beta) superfamily exert
      their effects by forming heteromeric complexes of their type I and type II
      serine/threonine kinase receptors. The type I and type II receptors form distinct
      subgroups in the serine/threonine kinase receptor family based on the sequences
      of the kinase domains and the presence of a highly conserved region called the GS
      domain (or type I box) located just N-terminal to the kinase domain in the type I
      receptors. Recent studies have revealed that upon TGF-beta binding several serine
      and threonine residues in the GS domain of TGF-beta type I receptor (T beta R-I)
      are phosphorylated by TGF-beta type II receptor (T beta R-II) and that the
      phosphorylation of GS domain is essential for TGF-beta signaling. Here we
      investigated the role of cytoplasmic juxtamembrane region located between the
      transmembrane domain and the GS domain of T beta R-I by mutational analyses using
      mutant mink lung epithelial cells, which lack endogenous T beta R-I. Upon
      transfection, wild-type T beta R-I restored the TGF-beta signals for growth
      inhibition and production of plasminogen activator inhibitor-1 (PAI-1) and
      fibronectin. A deletion mutant, T beta R-I/JD1(delta 150-181), which lacks the
      juxtamembrane region preceding the GS domain, bound TGF-beta in concert with T
      beta R-II and transduced a signal leading to production of PAI-I but not growth
      inhibition. Recombinant receptors with mutations that change serine 172 to
      alanine (S172A) or threonine 176 to valine (T176V) were similar to wild-type T
      beta R-I in their abilities to bind TGF-beta, formed complexes with T beta R-II,
      and transduced a signal for PAI-1 and fibronectin. Similar to T beta R-I/JD1
      (delta 150-181), however, these missence mutant receptors were impaired to
      mediate a growth inhibitory signal. These observations indicate that serine 172
      and threonine 176 of T beta R-I are dispensable for extracellular matrix protein
      production but essential to the growth inhibition by TGF-beta.

PMID- 8576254
TI  - Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein
      coupled receptor kinase 2 and protein kinase C.
AB  - Human muscarinic acetylcholine receptor m1 subtypes (m1 receptors) were expressed
      in and purified from insect Sf9 cells and then subjected to phosphorylation by G
      protein-coupled receptor kinase 2 (GRK2) expressed in and purified from Sf9 cells
      and by protein kinase C purified from rat brain (a mixture of alpha, beta, and
      gamma types, PKC). The m1 receptor was phosphorylated by either GRK2 or PKC in an
      agonist-dependent or independent manner, respectively. G protein beta gamma
      subunits stimulated the phosphorylation by GRK2 but did not affect the
      phosphorylation by PKC. The number of incorporated phosphates was 4.6 and 2.8
      mol/mol of receptor for phoshorylation by GRK2 and PKC, respectively. The number
      of incorporated phosphates was 7.5 mol/mol receptor for phosphorylation by GRK2
      followed by PKC, but was 5.8 mol/mol of receptor for the phosphorylation by PKC
      followed by GRK2. Major sites phosphorylated by GRK2 and PKC were located in the
      third intracellular loop and the carboxyl-terminal tail, respectively. These
      results indicate that GRK2 and PKC phosphorylate different sites of m1 receptors
      and that the phosphorylation by PKC partially inhibits the phosphorylation by
      GRK2, probably by affecting activation of GRK2 by agonist-bound receptors.

PMID- 8576255
TI  - Individual RNA recognition motifs of TIA-1 and TIAR have different RNA binding
      specificities.
AB  - TIA-1 and TIAR are two closely related RNA recognition motif (RRM) proteins which
      possess three RRM-type RNA binding domains (RRMs 1, 2, and 3). Although both
      proteins have been implicated as effectors of apoptotic cell death, the specific
      functions of TIA-1 and TIAR are not known. We have performed in vitro
      selection/amplification from pools of random RNA sequences to identify RNAs to
      which TIA-1 and TIAR bind with high affinity. Both proteins selected RNAs
      containing one or several short stretches of uridylate residues suggesting that
      the two proteins have similar RNA binding specificities. Replacement of the
      uridylate stretch with an equal number of cytidine residues eliminates the
      protein-RNA interaction. Mutational analysis indicates that, for both TIA-1 and
      TIAR, it is the second RNA binding domain (RRM 2) which mediates the specific
      binding to uridylate-rich RNAs. Although RRM 2 is both necessary and sufficient
      for this interaction, the affinity for the selected RNA (as determined by filter
      binding assays) does increase when the second domain of TIAR is expressed
      together with the first and third domains (Kd = 2 x 10(-8) M) rather than alone
      (Kd = 5 x 10(-8) M). Although RRM 3 (of either TIA-1 or TIAR) does not interact
      with the uridylate-rich sequences selected by the full-length proteins, it is a
      bona fide RNA binding domain capable of affinity-precipitating a population of
      cellular RNAs ranging in size from 0.5 to 5 kilobases. In contrast, RRM 1 does
      not affinity-precipitate cellular RNA. The inability of RRM 1 to interact with
      RNA may be due to the presence of negatively charged amino acids within the RNP 1
      octamer.

PMID- 8576256
TI  - Identification of a novel family of ubiquitin-conjugating enzymes with distinct
      amino-terminal extensions.
AB  - The ubiquitin/proteasome system is the main eukaryotic nonlysosomal protein
      degradation system. Substrate selectivity of this pathway is thought to be
      mediated in part by members of a large family of ubiquitin-conjugating (E2)
      enzymes, which catalyze the covalent attachment of ubiquitin to proteolytic
      substrates. E2 enzymes have a conserved approximately 150-residue so-called UBC
      domain, which harbors the cysteine residue required for enzyme-ubiquitin
      thioester formation. Some E2 enzymes possess additional carboxyl-terminal
      extensions that are involved in substrate specificity and intracellular
      localization of the enzyme. Here we describe a novel family of E2 enzymes from
      higher eukaryotes (Drosophila, mouse, and man) that have amino-terminal
      extensions but lack carboxyl-terminal extensions. We have identified four
      different variants of these enzymes that have virtually identical UBC domains
      (94% identity) but differ in their amino-terminal extensions. In yeast, these
      enzymes can partially complement mutants deficient in the UBC4 E2 enzyme. This
      indicates that members of this novel E2 family may operate in UBC4-related
      proteolytic pathways.

PMID- 8576257
TI  - Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and
      characterization of their interaction with E6-AP and RSP5.
AB  - E6-AP, a 100-kDa cellular protein, was originally identified through its
      interaction with the E6 protein of the oncogenic human papillomavirus types 16
      and 18. The complex of E6-AP and E6 specifically interacts with p53 and mediates
      ubiquitination of p53 in concert with the E1 ubiquitin-activating enzyme and the
      E2 ubiquitin-conjugating enzyme UbcH5. Recent results suggest that E6-AP is
      representative of a family of putative ubiquitin-protein ligases. Members of this
      family are characterized by a conserved C-terminal region, termed hect domain. In
      this paper, we describe the isolation of two human E2s, designated as UbcH6 and
      UbcH7, that in addition to UbcH5 can interact with E6-AP. UbcH6 is a novel member
      of an evolutionally conserved subfamily of E2s that includes UbcH5 and
      Saccharomyces cerevisiae UBC4. Although UbcH7 does not appear to be a member of
      this subfamily, UbcH7 efficiently substitutes for UbcH5 in E6-AP-dependent
      ubiquitination. Surprisingly, UbcH6 was only weakly active in this particular
      assay. In addition, UbcH5 but not UbcH6 or UbcH7 efficiently interacts with the
      heet protein RSP5. These results indicate that E6-AP can interact with at least
      two species of E2 and that different hect proteins may interact with different
      E2s.

PMID- 8576258
TI  - The neurotrophic activity of fibroblast growth factor 1 (FGF1) depends on
      endogenous FGF1 expression and is independent of the mitogen-activated protein
      kinase cascade pathway.
AB  - The expression of fibroblast growth factor (FGF) 1, a potent neurotrophic factor,
      increases during differentiation and remains high in adult neuronal tissues. To
      examine the importance of this expression on the neuronal phenotype, we have used
      PC12 cells, a model to study FGF-induced neuronal differentiation. After
      demonstrating that FGF1 and FGF2 are synthesized by PC12 cells, we investigated
      if FGF1 expression could be a key element in differentiation. Using the cell
      signaling pathway to determine the effects of FGF1 alone, FGF1 plus heparin, or a
      mutated FGF1, we showed an activation to the same extent of mitogen-activated
      protein (MAP) kinase kinase and MAP kinase (extracellular regulated kinase 1).
      However, only FGF1 plus heparin could promote PC12 cell differentiation. Thus,
      the MAP kinase pathway is insufficient to promote differentiation. Analysis of
      the PC12 cells after the addition of FGF1 plus heparin or FGF2 demonstrated a
      significant increase in the level of FGF1 expression with the same time course as
      the appearance of the neuritic extensions. Transfection experiments were
      performed to enhance constitutivly or after dexamethasone induction the level of
      FGF1 expression. The degree of differentiation achieved by the cells correlated
      directly with the amount of FGF1 expressed. The MAP kinase pathway did not appear
      to be involved. Interestingly, a 5-fold increase in FGF1 in constitutive
      transfected cells extended dramatically their survival in serum-free medium,
      suggesting that the rise of FGF1 synthesis during neuronal differentiation is
      probably linked to their ability to survive in the adult. All of these data
      demonstrate that, in contrast to the MAP kinase cascade. FGF1 expression is
      sufficient to induce in PC12 cells both differentiation and survival. It also
      shows that auto- and trans-activation of FGF1 expression is involved in the
      differentiation process stimulated by exogenous FGFs through a new pathway which
      remains to be characterized.

PMID- 8576259
TI  - Cardiac myotrophin exhibits rel/NF-kappa B interacting activity in vitro.
AB  - Myotrophin is a soluble-12 kilodalton protein isolated from hypertrophied
      spontaneously hypertensive rat and dilated cardiomyopathic human hearts. We have
      recently cloned the gene coding for myotrophin and expressed it in Escherichia
      coli. In the present study, the expression of myotrophin gene was analyzed, and
      at least seven transcripts have been detected in rat heart and in other tissues.
      We have further analyzed the primary structure of myotrophin protein and
      identified significant new structural and functional domains. Our analysis
      revealed that one of the ankyrin repeats of myotrophin is highly homologous
      specifically to those of myotrophin is highly homologous specifically to those of
      I kappa B alpha/rel ankyrin repeats. In addition, putative consensus
      phosphorylation sites for protein kinase C and casein kinase II, which were
      observed in I kappa B alpha proteins, were identified in myotrophin. To verify
      the significance of these homologies, kappa B gel shift assays were performed
      with Jurkat T cell nuclear extract proteins and the recombinant myotrophin.
      Results of these assays indicate that the recombinant myotrophin has the ability
      to interact with NF-kappa B/rel proteins as revealed by the formation of ternary
      protein-DNA complexes. While myotrophin-specific antibodies inhibited the
      formation of these complexes, rel-specific p50 and p65 antibodies supershifted
      these complexes. Thus, these results clearly indicate that the myotrophin protein
      to be a unique rel/NF-kappa B interacting protein.

PMID- 8576260
TI  - Characterization of a novel keratinocyte ubiquitin carrier protein.
AB  - A novel member of the ubiquitin carrier protein family, designated E2EPF, has
      been cloned by our laboratory and expressed in a bacterial system in an active
      form. Ubiquitin carrier proteins, or E2s, catalyze one step in a multistep
      process that leads to the covalent conjugation of ubiquitin to substrate
      proteins. In this paper, we show that recombinant E2EPF catalyzes
      auto/multiubiquitination, the conjugation of multiple ubiquitin molecules to
      itself. Multiubiquitination has been shown previously to be required for
      targeting of a substrate protein for rapid degradation. Using a rabbit
      reticulocyte lysate system, E2EPF was shown to support the degradation of a model
      substrate in an ATP- and ubiquitin-dependent fashion. In contrast to a previous
      study which showed that selective protein degradation in one system is dependent
      upon multiubiquitination via the lysine 48 residue of ubiquitin,
      multiubiquitination, and proteolytic targeting by E2EPF was shown here to be
      independent of the lysine 48 multiubiquitin linkage. This functional
      characterization of E2EPF revealed a combination of features that distinguishes
      this enzyme from all previously characterized members of the ubiquitin carrier
      protein family. These results also suggest several possible autoregulatory models
      for E2EPF involving auto- and multiubiquitination.

PMID- 8576261
TI  - Novel multiubiquitin chain linkages catalyzed by the conjugating enzymes E2EPF
      and RAD6 are recognized by 26 S proteasome subunit 5.
AB  - Targeting of substrates for degradation by the ATP, ubiquitin-dependent pathway
      requires formation of multiubiquitin chains in which the 8.6-kDa polypeptide is
      linked by isopeptide bonds between carboxyl termini and Lys-48 residues of
      successive monomers. Binding of Lys-48-linked chains by subunit 5 of the 26 S
      proteasome regulatory complex commits the attached target protein to degradation
      with concomitant release of free ubiquitin monomers following disassembly of the
      chains. Point mutants of ubiquitin (Lys-->Arg) were used to map the linkage
      specificity for ubiquitin-conjugating enzymes previously demonstrated to form
      novel multiubiquitin chains not attached through Lys-48. Recombinant human E2EPF
      catalyzed multiubiquitin chain formation exclusively through Lys-11 of ubiquitin
      while recombinant yeast RAD6 formed chains linked only through Lys-6.
      Multiubiquitin chains linked through Lys-6, Lys-11, or Lys-48 each bound to
      subunit 5 of partially purified human 26 S proteasome with comparable affinities.
      Since chains bearing different linkages are expected to pack into distinct
      structures, competition between Lys-11 and Lys-48 chains for binding to subunit 5
      demonstrates that the latter possesses determinants for recognizing alternatively
      linked chains and precludes the existence of subunit 5 isoforms recognizing
      distinct structures. In addition, competition studies provided an estimate of Kd
      < or = 18 nM for the intrinsic binding of Lys-48-linked chains of linkage number
      n > 4. This result suggests that the principal mechanistic advantage of
      multiubiquitin chain formation is to enhance the affinity of the associated
      substrate for the 26 S complex relative to that of unconjugated target protein.
      Complementation studies with E1/E2-depleted rabbit reticulocyte extract
      demonstrated RAD6 supported isopeptide ligase-dependent degradation only through
      Lys-48-linked chains, while E2EPF retained the ability to target a model
      radiolabeled substrate through Lys-11-linked chains. Therefore, the linkage
      specificity exhibited by these E2 isozymes depends on their catalytic context
      with respect to isopeptide ligase.

PMID- 8576262
TI  - Interleukin-8 regulation of the Ras/Raf/mitogen-activated protein kinase pathway
      in human neutrophils.
AB  - Interleukin-8 (IL-8), the prototypic member of the CXC subfamily of chemokines,
      induces in neutrophils chemotaxis, the respiratory burst, granule release, and
      increased cell adhesion. The IL-8 receptor is a seven-transmembrane spanning
      receptor coupled to specific heterotrimeric G proteins including Gi and G16. IL-8
      stimulation of its receptor on neutrophils activates Ras GTP loading and the
      mitogen-activated protein kinase (MAPK) pathway including Raf-1 and B-Raf. The
      properties of IL-8 stimulation of the MAPK pathway differ from those observed for
      chemoattractants such as C5a. Even though Ras GTP loading is similar for IL-8 and
      C5a, the maximal activation of Raf-1 and B-Raf is approximately 2-fold and 3-7
      fold, respectively, less for IL-8 than that observed for C5a. Raf-1 activation is
      rapid but transient, returning to near basal levels by 10 min. B-Raf activation
      is slower in onset and does not return to basal levels for nearly 30 min. IL-8
      activation of MAPK follows a time course suggesting an involvement of both Raf-1
      and B-Raf. Surprisingly, wortmannin, at low concentrations, inhibits Raf-1, B
      Raf, and MAPK activation in response to IL-8 and C5a demonstrating a role for
      phosphatidylinositol 3-kinase in the activation of Raf kinases in G protein
      coupled receptor systems in human neutrophils. Furthermore, wortmannin inhibits
      IL-8 stimulated granule release and neutrophil adherence. These findings
      demonstrate the control of Raf kinases, the MAPK pathway and specific neutrophil
      functions by phosphatidylinositol 3-kinase enzymes.

PMID- 8576263
TI  - Expression of phosphatidylethanolamine N-methyltransferase-2 is markedly enhanced
      in long term choline-deficient rats.
AB  - When rats are fed a choline-deficient (CD) diet, acute fatty liver develops along
      with other biochemical changes. However, when choline deficiency is prolonged,
      the growth rate of CD rats is similar to that of control rats fed a choline
      supplemented diet. Furthermore, CD rats maintain their levels of choline
      containing lipids, such as phosphatidylcholine, lysophosphatidylcholine, and
      sphingomyelin. The mechanism for this compensation in CD rats was investigated.
      We screened the major tissues for the activities of two important enzymes
      involved in the biosynthesis of phosphatidylcholine, CTP:phosphocholine
      cytidylyltransferase (CT) and phosphatidylethanolamine N-methyltransferase
      (PEMT). Only the livers of CD rats had higher specific enzyme activities of PEMT
      and CT than control animals. The amount of PEMT2, one of two PEMTs in liver,
      increased 5-fold in CD rats after 6 weeks on the CD diet. A similar increase in
      the level of PEMT2 mRNA suggested that this activation was due to enhanced
      expression of the PEMT2 gene in CD livers. The labeling of phosphatidylcholine in
      isolated hepatocytes from CD rats was consistent with the conversion of PE to PC
      being increased as a result of a higher expression of liver PEMT. We conclude
      that activation of PE methylation at the level of gene expression may be the
      mechanism by which CD rats compensate for the lack of dietary choline.

PMID- 8576264
TI  - cDNA cloning, expression, and mutagenesis study of leukotriene B4 12
      hydroxydehydrogenase.
AB  - Leukotriene B4 12-hydroxydehydrogenase catalyzes the conversion of leukotriene B4
      into its biologically less active metabolite, 12-oxo-leukotriene B4. This is an
      initial and key step of metabolic inactivation of leukotriene B4 in various
      tissues other than leukocytes. Here we report the cDNA cloning for porcine and
      human enzymes from kidney cDNA libraries. A full-length cDNA of the porcine
      enzyme contains an open reading frame consisting of 987 base pairs, corresponding
      to 329 amino acids. The human enzyme showed a 97.1% homology with the porcine
      enzyme. Northern blotting of human tissues revealed its high expression in the
      kidney, liver, and intestine but not in leukocytes. The porcine enzyme was
      expressed as a glutathione S-transferase fusion protein in Escherichia coli,
      which exhibited similar characteristics with the native enzyme. Because the
      enzymes have a homology, in part, with NAD(P)(+)-dependent alcohol
      dehydrogenases, a site-directed mutagenesis study was carried out. We found that
      three glycines at 152, 155, and 166 have crucial roles in the enzyme activity,
      possibly by producing an NADP+ binding pocket.

PMID- 8576265
TI  - Natural disruption of the mouse mast cell protease 7 gene in the C57BL/6 mouse.
AB  - The C57BL/6 mouse differs from the BALB/c mouse in that its ear and skin mast
      cells and its progenitor bone marrow-derived mast cells (mBMMCs) do not express
      mouse mast cell protease (mMCP) 7. We now report that, as detected by nuclear run
      on analysis, the mMCP-7 gene is transcribed in C57BL/6 mBMMCs at a rate
      comparable to that in BALB/c mBMMCs. Reverse transcriptase-polymerase chain
      reaction analysis and sequencing of the product revealed that the ears of C57BL/6
      mice contain small amounts of a mMCP-7 transcript that possesses a 98-base pair
      deletion. The deletion begins at a normally quiescent cryptic splice site
      (G416TGAG), 98 base pairs upstream of the normal exon 2/intron 2 splice site
      (G514TGAG), and introduces a premature stop codon in the alternatively spliced
      transcript. Thus, even if translated, the mature protein would consist of only 18
      amino acids as compared to 245 amino acids in normal mMCP-7. Sequence analysis of
      the mMCP-7 gene in the C57BL/6 mouse revealed that the cryptic splice site is
      activated due to a G514-->A point mutation at the first nucleotide of the normal
      exon 2/intron 2 splice site. This is the first report of a mutation of a gene
      that encodes a mast cell secretory granule constituent that leads to its loss of
      expression. Moreover, the mMCP-7 gene is the first found in any species that
      sequentially has undergone a splice site mutation to cause retention of an intron
      and then a second splice site mutation to cause activation of a cryptic splice
      site.

PMID- 8576266
TI  - CMP kinase from Escherichia coli is structurally related to other nucleoside
      monophosphate kinases.
AB  - CMP kinase from Escherichia coli is a monomeric protein of 225 amino acid
      residues. The protein exhibits little overall sequence similarities with other
      known NMP kinases. However, residues involved in binding of substrates and/or in
      catalysis were found conserved, and sequence comparison suggested conservation of
      the global fold found in adenylate kinases or in several CMP/UMP kinases. The
      enzyme was purified to homogeneity, crystallized, and analyzed for its structural
      and catalytic properties. The crystals belong to the hexagonal space group P6(3),
      have unit cell parameters a = b = 82.3 A and c = 60.7 A, and diffract x-rays to a
      1.9 A resolution. The bacterial enzyme exhibits a fluorescence emission spectrum
      with maximum at 328 nm upon excitation at 295 nm, which suggests that the single
      tryptophan residue (Trp30) is located in a hydrophobic environment. Substrate
      specificity studies showed that CMP kinase from E. coli is active with ATP, dATP,
      or GTP as donors and with CMP, dCMP, and arabinofuranosyl-CMP as acceptors. This
      is in contrast with CMP/UMP kinase from Dictyostelium discoideum, an enzyme
      active on CMP or UMP but much less active on the corresponding deoxynucleotides.
      Binding of CMP enhanced the affinity of E. coli CMP kinase for ATP or ADP, a
      particularity never described in this family of proteins that might explain
      inhibition of enzyme activity by excess of nucleoside monophosphate.

PMID- 8576267
TI  - Signaling through CD44 is mediated by tyrosine kinases. Association with p56lck
      in T lymphocytes.
AB  - Evidence from a large body of studies indicates that CD44 is involved in a number
      of important biological processes, including lymphocyte activation and homing,
      hematopoiesis, and tumor progression and metastasis. A proper understanding of
      the role of CD44 in these processes has been severely hampered by a lack of
      insight into the mode in which CD44 communicates with intracellular signal
      transduction pathways. In this report, we have addressed this aspect of CD44
      functioning by studying CD44 signaling in T lymphocytes. We show that ligation of
      CD44 by monoclonal antibodies (mAbs) transduces signals to T cells which lead to
      tyrosine phosphorylation of ZAP-70 and other intracellular proteins. In vitro
      kinase assays demonstrate that cross-linking of CD44 induces an increase in the
      intrinsic activity of p56lck. Furthermore, immunoprecipitations show that CD44 is
      physically associated with p56lck. Our findings suggest that tyrosine kinases,
      particularly p56lck, play a central role in CD44 mediated signaling.

PMID- 8576269
TI  - The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its
      inhibitory activities define the distinct TIMP gene family.

PMID- 8576268
TI  - Complete inhibition of human immunodeficiency virus Gag myristoylation is
      necessary for inhibition of particle budding.
AB  - Myristoylation of human immunodeficiency virus (HIV) Gag protein is essential for
      virus particle budding. Two reactions are involved; activation of free myristate
      to myristoyl-CoA and transfer of the myristoyl residue to the Gag N-terminal
      glycine. We have investigated the effects of triacsin C, an inhibitor of long
      chain acyl-CoA synthetase, on release of HIV Gag virus-like particle (VLP)
      produced using the recombinant baculovirus system. First, inhibition of acyl-CoA
      formation by triacsin C was confirmed using the membrane fractions of insect Sf9
      cells as an enzyme source. Second, when HIV Gag protein was expressed in the
      presence of triacsin C (0-48 microM), Gag myristoylation was inhibited in a dose
      dependent manner. Budding of Gag VLP, however, did not follow similar inhibition
      kinetics but appeared unaffected up to 24 microM, yet was completely abolished at
      48 microM when the myristoylation of Gag protein was also completely inhibited.
      The "all-or-none" inhibition of Gag VLP budding suggests that although inhibition
      of acyl-CoA synthetase blocks the production of myristoylated Gag protein, only
      complete inhibition of Gag myristoylation prevents VLP budding. Thus, relatively
      few myristoylated Gag molecules are sufficient for plasma membrane targeting and
      VLP budding.

PMID- 8576270
TI  - Two types of functionally different GABAA receptors mediate GABA modulation of
      cholinergic transmission in cat terminal ileum.
AB  - 1. The effects of GABA (1 microM-2 mM) on longitudinally or circularly oriented
      organ bath preparations of cat terminal ileum consisted of a relaxation phase
      with an inhibition of the rhythmic spontaneous phasic contractions, followed by a
      phase of contractions characterized by an elevation in basal tone and an increase
      in amplitude of the spontaneous phasic contractions. 2. Muscimol (100 microM),
      but not baclofen (100 microM), mimicked the relaxation phase of the response to
      applied GABA (100 microM) in all tissue preparations. In addition, muscimol
      induced a phase of contractile activity in the circular muscle layer whilst
      baclofen exerted a 'GABA-like' contractile effect on the longitudinal muscle
      layer. Bicuculline (30 microM) or picrotoxinin (30 microM) antagonized the GABA-
      or muscimol-induced relaxations in all preparations and decreased the GABA- but
      not the baclofen-induced contractions of the longitudinal muscle layer. 3.
      Tetrodotoxin (0.5 microM) or atropine (0.1 microM) prevented the bicuculline
      sensitive phases of the GABA or muscimol effects on both muscle layers but not
      the contractile effect of baclofen on the longitudinal muscle layer. 4. The
      bicuculline-sensitive phases of the GABA effect on both muscle layers were almost
      completely eliminated by 1 nM pirenzepine. At this concentration pirenzepine did
      not affect the electrically-evoked cholinergic twitch contractions or contractile
      responses to applied acetylcholine of both muscle layers. 5. During electrically
      evoked cholinergic twitch contractions of both muscle layers, GABA (100 microM)
      had an inhibitory effect. The inhibition occurred in the presence of pirenzepine
      (1 nM) but not of bicuculline (30 microM). 6. It is suggested that two types of
      functionally different bicuculline-sensitive GABAA receptors mediate an exitatory
      presynaptic and an inhibitory prejunctional action of GABA on the cholinergic
      transmission in cat terminal ileum.

PMID- 8576271
TI  - Effect of temperature reduction on the vas deferens hyperresponsiveness of
      sensitized mice.
AB  - 1. The present study was designed to investigate the effect of active
      sensitization on the responsiveness of mouse vas deferens before and after
      moderate cooling. Contractile responses to noradrenaline (NA) were isometrically
      recorded in the vas deferens of control and ovalbumen-sensitized mice at 37
      degrees C and 22 degrees C. 2. Enhancement of the vas deferens reactivity to NA
      was observed in the sensitized vs control mice at 37 degrees C and 22 degrees C
      (P < 0.01). In sensitized mice, maximal contraction was significantly increased
      compared with controls, and sensitization-induced hyperresponsiveness was greater
      at 22 degrees C compared with 37 degrees C. At 37 degrees C, contractile
      responses to barium chloride were significantly enhanced in the sensitized mice
      compared with controls, whereas the reduction of the temperature to 22 degrees C
      produced a marked inhibition of vas deferens contractions in both groups.
      Caffeine-induced contractions of the vas deferens were similar in control and
      sensitized mice at 37 degrees C. After moderate cooling to 22 degrees C, vas
      deferens from sensitized mice became hyperresponsive compared with controls. 3.
      Ouabain (0.1 mM) produced an increase of NA-induced contraction in control and
      sensitized vas deferens at 37 degrees C (P < 0.01). It had no significant effect
      in the control at 22 degrees C but produced a marked inhibition of NA-induced
      contraction in the sensitized vas deferens at 22 degrees C. Contractions to NA in
      the presence of vanadate (1 mM) were depressed in control and sensitized mice at
      both temperatures. 4. These results suggest that sensitization-induced
      hyperresponsiveness of the mouse vas deferens is mediated by an increased
      mobilization of intracellular calcium. The involvement of an unknown ouabain
      sensitive pathway in sensitization-induced alterations is also discussed.

PMID- 8576272
TI  - Effects of chronic infusion of (-)-isoprenaline on rat cardiac muscarinic (M2)
      cholinoceptors and beta 1- and beta 2-adrenoceptors.
AB  - 1. The effects of chronic (-)-isoprenaline infusion (400 micrograms kg-1 h-1; 4 h
      14 days) on rat ventricular muscarinic M2-cholinoceptors and beta 1- and beta 2
      adrenoceptors was determined. [3H]-N-methylscopolamine (NMS) was used to measure
      M2-cholinoceptor binding and (-)-[125I]-cyanopindolol (CYP) was used for beta 1-
      and beta 2-adrenoceptor binding. 2. Chronic infusion of (-)-isoprenaline did not
      affect either the affinity of [3H]-NMS for M2-cholinoceptors, or the maximal
      density of these receptors (Bmax) at all treatment periods investigated (4 and 20
      h; 7 and 14 days). The affinity of (-)-[125I]-CYP for beta-adrenoceptors was not
      changed following chronic (-)-isoprenaline infusion (4, 12 and 20 hours; 7 and 14
      days). 3. Competition between (-)-[125I]-CYP and the selective beta 1
      adrenoceptor antagonist CGP 20712A resulted in biphasic curves at all treatment
      periods corresponding to the presence of beta 1- and beta 2-adrenoceptor binding
      sites. beta 1-adrenoceptors made up the greater proportion of beta-adrenoceptors
      in rat ventricle. There was no change in the ratio of beta 1- to beta 2
      adrenoceptors following 4 h (-)-isoprenaline infusion [(beta 1:beta 2), vehicle:
      77.5 +/- 4.0%:22.5 +/- 4.0%, n = 6; (-)-isoprenaline: 79.2 +/- 1.2%:20.8 +/-
      1.2%, n = 6], however infusion for 12 h increased the ratio [(beta 1:beta 2),
      vehicle: 65.2 +/- 6.1%:34.8 +/- 6.1%, n = 6; (-)-isoprenaline: 85.6 +/- 1.8%:14.4
      +/- 1.8%, n = 6, P < 0.05], which was maintained for longer infusion periods (20
      h-14 days). 4. Both beta 1- and beta 2-adrenoceptors were down-regulated in rat
      ventricular tissue following (-)-isoprenaline infusion. beta 2-adrenoceptors were
      down-regulated by 12 h (vehicle: 11.8 +/- 2.4 fmol mg protein-1, n = 6; (-)
      isoprenaline: 3.5 +/- 0.4 fmol mg protein-1, n = 6, P < 0.05) however beta 1
      adrenoceptors were not affected (vehicle: 21.7 +/- 2.0 fmol mg protein-1, n = 6;
      (-)-isoprenaline: 20.9 +/- 0.6 fmol mg protein-1, n = 6, P > 0.05) until 20 h
      infusion (vehicle: 19.4 +/- 2.2 fmol mg protein-1, n = 6; (-)-isoprenaline: 12.6
      +/- 2.2 fmol mg protein-1, n = 6, P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8576273
TI  - Effects of Bay K 8644 in aorta from spontaneously hypertensive and Wistar Kyoto
      rats of different ages.
AB  - 1. The Ca(2+)-channel agonist, Bay K 8644, induced small contractions in aortae
      from Wistar-Kyoto (WKY) rats of 5-week-, 3-month-, 1-year- and 1.5-year-old,
      which were unaltered with age. These contractions were increased by partial
      depolarization with 15 mM K+. 2. In segments from spontaneously hypertensive rats
      (SHR), the contractions obtained in both situations were similar and equivalent
      to those observed in segments from normotensive animals partially depolarized.
      Responses to Bay K 8644 were modified by age only in tissues from the SHR, the
      responses to this agent in basal conditions being increased in tissues from 3
      month- and 1-year-old animals and depressed in those from 1.5-year SHR. 3. A
      reduction of the response to Bay K 8644 was observed in partial depolarized
      endothelium denuded segments from WKY of all ages, and no modification in basal
      situation. However, the direct contractions induced by Bay K 8644 in aortae from
      3-month- and 1.5-year-old SHR were reduced by endothelium removal. 4. These
      results suggest that: (a) in the hypertensive strain the voltage-gated Ca2+
      channels seem to be partially activated; (b) the direct contractions induced by
      Bay K 8644 were unaltered by age in aortae from WKY but increased in tissues from
      SHR of 3-month-and-1-year old and depressed in those from 1.5 years, and (c) the
      contractions evoked by Bay K 8644 seem to involve an endothelium-derived
      contracting factor in aortae from both strains, or the endothelium produces a
      partial depolarization of vascular smooth muscle that increases the
      responsiveness to Bay K 8644.

PMID- 8576274
TI  - Identification of alpha 1-adrenoceptor subtypes in the rabbit prostate.
AB  - 1. The alpha 1-adrenoceptor subtypes of rabbit prostate were characterized in
      binding and functional experiments. 2. In saturation experiments, [3H]-prazosin
      bound to two distinct affinity sites in the rabbit prostate (pKD = 11.20 +/- 0.22
      and 8.39 +/- 0.11, Bmax = 15.3 and 736 fmol mg protein-1). 3. In the displacement
      experiments, the binding was inhibited with shallow displacement curves by
      unlabelled prazosin, WB4101, and 5-methylurapidil, suggesting the presence of two
      distinct affinity sites for prazosin, WB4101, or 5-methylurapidil. On the other
      hand, HV723 displaced the [3H]-prazosin binding monophasically with a low
      affinity. From the results, the presence of two distinct alpha 1-adrenoceptor
      subtypes was suggested; presumably one is the classical alpha 1A (cloned alpha
      1C) subtype with high affinity for prazosin, WB4101 and 5-methylurapidil but not
      for HV723 and the other corresponds to the alpha 1L subtype, which shows low
      affinity for the four antagonists. 4. In the functional experiments, prazosin,
      WB4101, HV723 and 5-methylurapidil competitively antagonized the contractile
      response to noradrenaline with low affinities close to those for the alpha 1L
      subtype determined in binding experiments. These results suggest that contractile
      response to noradrenaline in the rabbit prostate is predominantly mediated
      through the alpha 1L subtype.

PMID- 8576275
TI  - Nitric oxide, oxygen-derived free radicals and vascular endothelium.

PMID- 8576276
TI  - Oral antitumour activity in murine L1210 leukaemia and pharmacological properties
      of liposome formulations of N4-alkyl derivatives of 1-beta-D
      arabinofuranosylcytosine.
AB  - The oral cytostatic activity in L1210 mouse leukaemia of the two new N4-alkyl
      derivatives of 1-beta-D-arabinofuranosylcytosine (AraC), N4-hexadecyl- and N4
      octadecyl-1-beta-D-arabinofuranosylcytosine (NH-AraC, NO-AraC) was investigated.
      In contrast to AraC, both derivatives were highly cytostatic after oral
      application as liposome formulations. With treatment schedules of five
      consecutive dosages or with two applications on days 1 and 4 after intravenous
      tumour cell inoculation with a total dose of 470-1000 mg/kg NH-AraC or NO-AraC,
      70%-100% of the treated animals were cured. The lethal dose in healthy ICR mice
      after a single intraperitoneal application, corresponding to the LD50, was 524
      mg/kg for NO-AraC, whereas NH-AraC proved to be less toxic. The haematological
      toxicity remained moderate for both drugs with a mild leucopenia and a drop in
      platelet counts, which recovered 4-6 days after treatment. The erythrocytes were
      not affected and haemolytic toxicities were absent. As non-haematological
      toxicities, at high drug concentrations, a pronounced atrophy of the rapidly
      dividing epithelia of the small intestines and of the white pulp of the spleen
      were observed. The blood levels of NH-AraC given orally reached values comparable
      to those after parenteral application of a four-times lower dose of NH-AraC,
      suggesting a moderate bioavailability. Thus, these two lipophilic derivatives of
      AraC are compounds with a potential for the oral treatment of malignant diseases.

PMID- 8576277
TI  - Cellular pharmacokinetics of ZD1694 in cultured human leukaemia cells sensitive,
      or made resistant, to this drug.
AB  - We have analysed the cellular metabolism of a novel thymidylate synthase (TS)
      inhibitor, ZD1694, in MOLT-3 and K562 human leukaemia cell lines sensitive to or
      made resistant to ZD1694 by continuous exposure of the cells to ZD1694 with
      stepwise escalation of the drug concentration. The initial cellular uptake of
      [3H]ZD1694 was greater in K562 cells than in MOLT-3 cells and the drug
      accumulated approximately 3-fold more in the former cells following incubation
      with 0.1 microM ZD1694 at 37 degrees C for 24 h. TS and dihydrofolate reductase
      activities were not significantly different between the two cell lines. After a
      30-min incubation with the drug at 37 degrees C, 85% of the total drug (2.3
      pmol/mg protein) in K562 cells was found as tri- to pentaglutamates, whereas MOLT
      3 cells accumulated less drug in this time (0.83 pmol/mg protein) and
      polyglutamates of chain length greater than triglutamate were not found to a
      significant extent. When the incubation time was extended to 24 h, the
      polyglutamate profile in K562 cells was progressively shifted towards those of
      long glutamate chain length and 59% of the total cellular drug (204 pmol/mg
      protein) was identified as the penta form. In contrast, even distribution between
      tri- and pentaglutamate was observed in MOLT-3 cells. Total cellular
      polyglutamates were approximately 3-fold higher in K562 cells than in MOLT-3
      cells, and this may explain the 2.5-fold difference in the sensitivity to ZD1694
      between the two cell lines. Continuous exposure of MOLT-3 and K562 cells to
      ZD1694 up to 1 microM or 0.1 microM resulted in 1600- and 4200-fold resistant
      sublines, respectively (MOLT-3/ZD1694.C and K562/ZD1694.C). The resistant MOLT-3
      cells showed a markedly lower cellular accumulation and poor retention of
      [3H]ZD1694 with no significant change of initial drug uptake by 10 min and with a
      little increase of TS activity. HPLC analysis demonstrated that more than 90% of
      the 3H co-eluted with the monoglutamate (parent drug) in the resistant MOLT-3
      cells, indicating extremely diminished polyglutamation in the cells. On the other
      hand, cellular uptake of [3H]ZD1694 was extensively impaired in K562/ZD1694.C
      cells and cellular accumulation of the drug was only 2.5% of that in the parent
      cells following 24 h incubation with the drug. Neither an increase of TS or
      dihydrofolate reductase activity nor a change in the polyglutamate formation
      profile was observed in the resistant K562 cells. These results indicate that the
      cellular ability to produce the polyglutamate metabolites of ZD1694 must
      influence the sensitivity of the tumour cells to this drug, and development of
      mechanisms involved in the ZD1694 resistance may relate to the intrinsic
      biochemical properties of the cells.

PMID- 8576278
TI  - The neu oncogene product in serum and tissue of patients with metastatic
      gastrointestinal carcinomas.
AB  - We report on our experience investigating the serum levels of the soluble domain
      of p185 and the neu protein expression in the corresponding tumour tissue in
      patients with advanced gastrointestinal carcinomas. The study included 32
      patients who were treated with palliative chemotherapy. The serum levels of the
      neu protein were investigated by immunosorbent assay techniques. We used the
      alkaline phosphatase/anti-(alkaline phosphatase) method for investigating the
      corresponding tumour tissue immunohistochemically. Increased serum neu protein
      levels were found in 8 of 22 (36%) patients with colorectal carcinomas and in 2
      patients with advanced abdominal adenocarcinoma of unknown primary. All other
      patients with advanced gastrointestinal cancers were serum-neu-protein-negative.
      All serum-neu-protein-positive patients with colorectal carcinomas showed also an
      elevated neu protein expression. The extent of serum neu protein expression
      corresponded to the clinical course and the tumour marker CA 19-9. The serum neu
      protein may be useful for monitoring patients with advanced colorectal
      carcinomas, particularly in cases of immunohistochemical neu-protein-positive
      primary tumours.

PMID- 8576279
TI  - Different expression patterns of cyclins A, D1 and E in human colorectal cancer.
AB  - The expressions of cyclins A, D1 and E at the protein level were investigated by
      Western blotting in human colorectal carcinomas and in adjacent non-neoplastic
      colorectal mucosas. Cyclin E was higher in the cancer tissue than in the non
      neoplastic mucosa in 92% patients (35 out of 38 cases). However, the cyclin A
      expression of the mucosa was higher than that of the cancer tissue in 63% (25 out
      of 40 cases) cases, and only 4 (10%) cancers had higher cyclin A expression.
      Eleven cancers (27%) demonstrated expression equivalent to that in the mucosa.
      Equal expression of cyclin D1 in cancer and mucosal tissues was found in 51%
      cases (20/39), lower expression of cyclin D1 by cancer tissues was demonstrated
      in 41% cases (16/39) and only three cancers showed higher expression than the
      mucosa. Proliferating-cell nuclear antigen immunohistochemistry revealed that the
      labeling index of the cancer tissue was 43.5 +/- 8.3% while that of the mucosa
      was only 14.8 +/- 5.1%. These results proved that colorectal cancers express high
      levels of cyclin E, consistent with a high rate of cell proliferation, whereas
      most of such cancer lose control of cyclin A and cyclin D1 expression.

PMID- 8576280
TI  - DNA ploidy level assessments in 83 human brain metastases. Relationship to the
      survival of 35 patients.
AB  - The nuclear DNA content (DNA ploidy) level was determined in a series of 83 human
      brain metastases, for which 35 complete clinical follow-ups were available. The
      DNA ploidy level determination was carried out by means of DNA histogram types.
      The results show that certain brain metastases were diploid, while others
      exhibited aneuploidy levels ranging from low to very high. The present study also
      shows that a significant proportion, i.e. 18%, of the 83 brain metastases,
      exhibited very high levels of aneuploidy, i.e. hypertetraploidy, hyperpentaploidy
      and octoploidy. We have previously observed that this feature appeared only
      rarely, i.e. in less than 2% of primary nervous tumours. Furthermore, the present
      study shows that DNA ploidy level in brain metastases is related significantly (P
      < 0.001) to patient survival. Indeed, while 9/13 (69%) patients with diploid
      brain metastases survived longer than 9 months, none (0%) of the 22 patients with
      aneuploid brain metastases survived longer than the 9 months following the
      diagnosis of their brain metastases.

PMID- 8576281
TI  - Granisetron-induced acute pancreatitis.

PMID- 8576282
TI  - Paclitaxel in the management of ovarian cancer: what we know and what we have yet
      to learn.

PMID- 8576283
TI  - Breast cancer surgery: a century after Halsted.
AB  - In the early years of this century prevailing currents of medical opinion led to
      the imposition of surgery even more aggressive than the radical mastectomy
      proposed by Halsted to treat breast cancer. More recently breast conservation
      surgery has become established but is always flanked by additional local
      treatment, and often by systemic therapy. Studies conducted in Milan were the
      first to demonstrate that conservative surgery plus an adjuvant therapy such as
      radiotherapy is efficacious in treating small-size breast cancer. As the year
      2000 approaches it has become clear that breast cancer is curable in a high
      proportion of cases and attention is turning to improving the aesthetic outcome
      of the surgery, and to investigating the biological and genetic factors that
      influence the disease.

PMID- 8576285
TI  - Establishment and characterization of a human colon cancer cell line, OUMS-23,
      from a patient with familial adenomatous polyposis.
AB  - A human colon carcinoma cell line designated OUMS-23 has been established from
      metastatic pericardial fluid of a male familial adenomatous polyposis patient
      with colon cancer. Since 1984, the epithelial cells have been maintained in
      culture. Ultrastructural studies revealed the presence of numerous microvilli on
      the cell surface and desmosomes between the adjacent cells. The cells secreted
      carcinoembryonic antigen into the culture medium (15 ng/10(6) cells-1 24 h-1).
      The cells expressed heat-stable placental-type-like alkaline phosphatase, whereas
      the normal counterparts expressed tissue-unspecific alkaline phosphatase.
      Karyotypic analysis showed that the cell line was of human origin and that the
      chromosome number was broadly distributed between 53 and 118. Southern blot
      analysis of the APC gene revealed no abnormalities in OUMS-24 cells, while
      Northern blot analysis demonstrated that the expression of the gene was about one
      half that of the normal human fibroblasts. No mutations at the "hot spots" of
      codons 12 and 61 of H-, K- and N-ras proto-oncogenes were detected in the cells.
      The cells could grow in soft agar at a cloning efficiency of 6.5%, and upon
      transplantation into nude mice the cells formed tumors, which were diagnosed as
      differentiated adenocarcinoma.

PMID- 8576284
TI  - Preferential inhibition of DNA polymerases alpha, delta, and epsilon from
      Novikoff hepatoma cells by inhibitors of cell proliferation.
AB  - DNA polymerases alpha, delta and epsilon from normal regenerating rat liver and
      Novikoff hepatoma cells were purified about 300-fold, characterized, and checked
      for sensitivity towards drugs known to inhibit cell proliferation.
      Characterization included (a) identification of associated proteins, (b)
      measurement of physiochemical constants (including sedimentation coefficients,
      diffusion coefficients, calculation of relative molecular masses), (c)
      quantification of catalytic activities using specific DNA primer templates (Km
      values) and specific inhibitors (Ki values), and (d) discrimination between DNA
      polymerases from normal cells and those from malignant cells using inhibitors of
      cell proliferation. (a) DNA primase associated with DNA polymerase alpha, and 3'
      5' exonuclease accompanying DNA polymerases delta and epsilon had similar
      activities. (b) Comparison of physicochemical and catalytic properties of DNA
      polymerases from both sources revealed similarities but also some important
      differences. Sedimentation and diffusion coefficients of DNA polymerases alpha
      and epsilon from malignant cells differed significantly. (c) The DNA-binding
      domain of DNA polymerases alpha and epsilon from hepatoma cells was altered since
      Km values, determined with several specific DNA primer-templates, were higher.
      Furthermore, dNTP-binding sites of DNA polymerases from malignant cells, when
      probed with specific inhibitors (aphidicolin, butylphenyl-dGTP,
      carbonyldiphosphonate, and dideoxy-TTP) showed significantly lower Ki values,
      indicating lower affinity to deoxyribonucleoside 5'-triphosphates. (d) Sixteen
      drugs representative of various modes of interaction with DNA and protein were
      chosen. Dose/response experiments were performed and the concentration at which
      the polymerizing activity was reduced to 50% was calculated (K50 values).
      Preferential inhibition of DNA polymerases alpha, delta, and epsilon from
      Novikoff hepatoma cells was found for: the intercalating drugs doxorubicin,
      daunorubicin, amsacrine, mitoxantrone, quinacrine and ethidium bromide, the minor
      groove binders distamycin and netropsin, the ATPase-blocking agents novobiocin
      and coumamycin, and the topoisomerase I inhibitors camptothecin and topotecan.
      When the sensitivity of polymerases delta and epsilon was measured using
      poly(dA.dT) as a primer-template, the preferential inhibition of the enzymes from
      malignant cells was even more pronounced. Drugs known to trap the DNA
      topoisomerase-II complex, etoposide, nalidixic acid, teniposide, and merbarone
      did not affect DNA polymerases irrespective of the source. Since the majority of
      the inhibitors used, particularly intercalators and minor-groove binders, act by
      modification of the primer-template, inhibition of DNA synthesis must have
      occurred through weakening of non-covalent bonds between DNA and catalytic
      polypeptides. Consequently, preferential inhibition of DNA polymerases from
      malignant cells seems to be indicative of abnormally diminished binding of the
      enzymes to their primer-templates. This effect may be caused by conformational
      alterations in polymerases from malignant cells which affect the DNA binding
      domains. Similarly, changes in physicochemical and kinetic constants are
      indicative of alterations of dNTP-binding domains.

PMID- 8576286
TI  - Structure-odor relationships: using neural networks in the estimation of
      camphoraceous or fruity odors and olfactory thresholds of aliphatic alcohols.
AB  - Structure-odor relationships were established for a sample of 99 aliphatic
      alcohols using a three-layer backpropagation neural network. The molecular
      structure was described using a common skeleton with six possible substitutions.
      Substituents were described using only their van der Waals volumes. The
      discrimination between fruity and camphoraceous odors of 67 compounds gave good
      results in classification (100%) and prediction (85%) phases. With the global
      set, the network correctly classified and predicted the camphoraceous character
      of compounds (100% and 95% respectively) but gave poorer results for the fruity
      character (87% and 74% respectively). Calculations of pOLs (pOL = -log (olfactory
      threshold expressed in mol/L)) of 45 camphoraceous compounds were also made. When
      all camphoraceous compounds were used to establish the model, 91% of the pOLs
      were correctly estimated. When attempts were made to predict the pOL values of
      10% of the compounds from a model designed using 90% of the sample, only 74% of
      the pOLs were correctly estimated.

PMID- 8576287
TI  - Quantum pharmacological analysis of structure-activity relationships for
      mefloquine antimalarial drugs using optimal transformations.
AB  - Optimal nonlinear transformations provided by alternating conditional
      expectations (ACE) method are used to study the relationship between electronic
      structure and antimalarial activity of mefloquine and its substituted
      derivatives. The electronic structure of these molecules is featured by atomic
      net charges evaluated on the basis of CNDO/2 molecular orbital calculations. A
      comparison to multiple linear regression (MLR) and partial least squares (PLS)
      method is also included. The results show that ACE can be a useful and well
      suited technique for establishing QSAR and predicting the pharmacological
      activity of compounds.

PMID- 8576288
TI  - MOLMAKER: de novo generation of 3D databases for use in drug design.
AB  - A program, MOLMAKER, is described which, in conjunction with a 2D-3D conversion
      program and 3D database software, can generate de novo 3D databases to aid in
      drug design. MOLMAKER is based upon graph-theoretical techniques for vertex
      degree set generation and constructive enumeration of molecular graphs. The
      generated molecular graphs are then functionalised in a probabilistic manner but
      in accordance with various constraints specified by the user. The resulting
      connection tables can be converted into 3D structures by commercial software and
      loaded into a 3D database for pharmacophore searching. The utility of MOLMAKER is
      illustrated by two examples of interest from the recent scientific literature:
      the design of novel protein kinase C agonists and of a bridging ligand for
      cyclophilin-calcineurin.

PMID- 8576289
TI  - Using neural networks to predict the onset of diabetes mellitus.
AB  - Classification is an important decision making tool, especially in the medical
      sciences. Unfortunately, while several classification procedures exist, many of
      the current methods fail to provide adequate results. In recent years, artificial
      neural networks have been suggested as an alternative tool for classification.
      Here, we use neural networks to predict the onset of diabetes mellitus in Pima
      Indian women. The modeling capabilities of neural networks are compared to
      traditional methods like logistic regression and to a specific method called
      ADAP, which has been used to predict diabetes. The results indicate that neural
      networks are indeed a viable approach to classification. Furthermore, we attempt
      to provide a basis upon which neural networks can be used for variable selection
      in statistical modeling.

PMID- 8576290
TI  - Some historical comments on quarantine: Part Two.

PMID- 8576291
TI  - Expanded gentamicin volume of distribution in critically ill adult patients
      receiving total parenteral nutrition.
AB  - Aminoglycoside antibiotics distribute into the extracellular fluid compartment
      and are eliminated by the kidney via glomerular filtration. Malnutrition and
      total parenteral nutrition influence the fluid and electrolyte status of the
      patient, and cause organ changes. The purpose of this clinical study was to
      characterize the kinetic behaviour of gentamicin in the parenterally fed
      critically ill adult patient. Eighty-six critically ill adult patients treated
      with gentamicin for severe Gram-negative infections were enrolled in the study
      (mean +/- SD): age, 60 +/- 14 years; weight, 69.4 +/- 10.2 kg; height, 163 +/- 10
      cm; 22 females and 64 males. Four study groups were defined (2 x 2): total
      parenteral nutrition vs. fluid therapy, and acute renal failure vs. normal renal
      function. The drug was administered by intermittent intravenous infusion. Blood
      samples were drawn at steady-state, 5 min before the next dose ('trough') and 30
      min after the termination of the infusion ('peak'). Gentamicin serum
      concentration was determined by fluorescence polarization immunoassay. Gentamicin
      pharmacokinetic parameters were estimated by non-linear regression analysis,
      assuming a one-compartment model and first-order elimination from the central
      compartment. Treatment of malnutrition with total parenteral nutrition increased
      gentamicin volume of distribution (P < 0.001), but did not affect total body
      clearance (P = 0.75). This change tended to produce lower peak concentrations (<
      4 micrograms/ml, P = 0.07), thus potentially compromising therapeutic
      effectiveness. There was no significant influence on trough concentrations (P =
      0.56). Patients receiving fluid therapy had a volume of distribution of 0.34 +/-
      0.08 litre/kg, while those fed by the intravenous route showed larger values
      (0.43 +/- 0.12 litre/kg), irrespective of their renal function. This may be
      explained by the extracellular water expansion caused by stress, malnutrition,
      and parenteral refeeding. Gentamicin dosage regimens in critically ill adult
      patients on total parenteral nutrition should be formulated on the basis of
      larger volumes of distribution and to attain therapeutic serum concentrations
      higher doses may be required.

PMID- 8576292
TI  - Serum beta-carotene, vitamin E, vitamin C and malondialdehyde levels in several
      types of cancer.
AB  - We measured the levels of serum carotenoids (beta-carotene), total tocopherol
      (vitamin E), ascorbic acid and malondialdehyde (MDA) in newly diagnosed cancer
      cases. Levels of the antioxidants and MDA in serum samples from 208 subjects with
      cancer affecting different sites (59 breast, 38 head and neck, 46 genitourinary,
      12 lung, 20 gastrointestinal and 33 other sites) were compared with levels in 156
      controls. Cases and controls were compared with respect to a number of
      potentially confounding factors: age, sex, smoking status, Quetelet index
      (kg/m2), diet and alcohol intake. Mean (+/- SD) levels of beta-carotene, vitamin
      E and vitamin C were significantly lower among the cases than the controls (49.35
      +/- 36.55 micrograms/l, 0.60 +/- 0.14 mg/dl, 0.40 +/- 0.27 mg/dl and 75.31 +/-
      28.59 mg/dl, 0.98 +/- 0.13 mg/dl, 0.88 +/- 0.47 mg/dl, respectively) (P < 0.05).
      On the other hand, mean levels of MDA were significantly higher among the cases
      than the controls (6.79 +/- 1.22 nmol/ml and 3.52 +/- 0.97 nmol/ml, respectively)
      (P < 0.05). The results obtained suggest that measurement of serum antioxidants
      and MDA levels may provide further useful information when evaluating cancer
      patients.

PMID- 8576293
TI  - Chemical stability of fluocinolone acetonide ointment and fluocinonide cream
      diluted in emollient bases.
AB  - The chemical stability of fluocinolone acetonide ointment and fluocinonide cream
      was studied when diluted in emollient bases. Fluocinolone acetonide ointment was
      diluted 1 in 4 with Unguentum Merck and Lipobase. Fluocinonide cream was also
      studied in these bases, with the addition of Metosyn Diluent, at dilutions of 1
      in 4 and 1 in 10. Regression analysis gave the time for 5% degradation of
      fluocinolone acetonide at a dilution of 1 in 4 in Unguentum Merck and in Lipobase
      as 12 weeks in both cases. The lower 95% confidence bound of each regression line
      was used to set shelf lives, for additional safety, and gave values of 1 month
      for the Unguentum Merck dilution and 2 months for the Lipobase dilution.
      Fluocinonide dilutions were more stable than the corresponding fluocinolone
      acetonide dilutions, with no degradation detectable during the study. The base
      made no observable difference to stability. Shelf lives, based on the lower 95%
      confidence bound of the regression data, of more than 6 months would be feasible
      for all of the fluocinonide 1 in 4 dilutions studied and for the 1 in 10 dilution
      in Unguentum Merck. However, for fluocinonide 1 in 10 in Metosyn Diluent, a shelf
      life of only 6 weeks could be assured, due to there being more variation in the
      analytical results. There were insufficient data to determine a storage life
      based on the lower 95% confidence bound of the regression for fluocinonide 1 in
      10 in Lipobase. More data would be required to determine if there was significant
      interbatch variation in the stability of the dilutions.

PMID- 8576294
TI  - Prevalence of intestinal parasites and association with symptoms in Southeast
      Asian refugees.
AB  - We prospectively evaluated 201 Southeast Asian refugees in a primary care clinic
      for intestinal parasites and their association with gastrointestinal symptoms.
      Patients completed a standardized screening questionnaire which elicited
      information on demographic factors and eight gastrointestinal symptoms, and
      stools were collected for ova and parasite examination. Although 89% had been
      living in the U.S.A. for more than 1 year, intestinal parasites were found in 37
      (18%) patients and pathogenic parasites in 23 (11%). Among these 37 patients with
      intestinal parasites, seven (19%) had multiple parasites. Seven pathogenic and
      four nonpathogenic species were identified. Hookworm was most prevalent (4.5%),
      followed by Strongyloides stercoralis (2.5%) and Clonorchis sinensis (2%).
      Cambodians had the highest prevalence (11%) and Vietnamese and highland Laotians
      the lowest (0%). Intestinal parasitosis was not associated with gender or
      duration of residence in the U.S.A. Individual symptoms had a low positive
      predictive value for the presence of pathogenic parasites. This suggests that
      even years after immigration a substantial number of Southeast Asian refugees may
      benefit from screening and treatment for intestinal parasites.

PMID- 8576295
TI  - A double-blind crossover comparison study of the safety and efficacy of
      mebeverine with mebeverine sustained release in the treatment of irritable bowel
      syndrome.
AB  - The safety and efficacy of the sustained release (SR) mebeverine capsule was
      compared to the standard plain mebeverine capsule in the treatment of 60 patients
      suffering from irritable bowel syndrome. Patients, with a score of at least 44 on
      the Kruis scale, were randomized into a two-period crossover trial. Each
      treatment period lasted for 6 weeks during which the patients took mebeverine
      plain 135 mg, two capsules t.i.d., or mebeverine sustained release 200 mg (SR),
      two capsules b.i.d. After 6 weeks of each treatment, both treatments were
      regarded 'effective' or 'very effective' by the patient as well as the
      investigator in more than 80% of the cases. After 3 weeks of the first treatment,
      the disease score was rated light in 73% of the patients with both medications.
      After 6 weeks, nine patients (33%) were symptom-free with mebeverine plain, and
      five (18%) with mebeverine SR. During the second treatment period the number of
      symptom-free cases reached about 40% with both formulations. Considering the
      clinical general improvement, more than 70% of all patients had improved after 3
      weeks of the first treatment. An additional improvement was reported in 13
      patients with mebeverine plain and in 10 patients with mebeverine SR after the
      next 3 weeks. Abdominal pain was still present in more than 50% of patients but
      with lower intensity compared with baseline values. Mean scores of efficacy were
      very similar for both treatments after 3 and 6 weeks (2.0 for mebeverine plain
      vs. 1.9 for mebeverine SR). The statistical comparison of all scores between the
      two formulations did not show a significant difference at any time. Very few
      adverse events were noted and a causal relationship with the study medications
      was judged as improbable or definitely unrelated. Compliance was close to 100%
      for most of the patients. The results of the present study indicate that the
      mebeverine SR capsule provides equivalent efficacy and tolerance to mebeverine
      plain in the treatment of irritable bowel syndrome (IBS), while reducing the
      number of daily doses from three to two.

PMID- 8576296
TI  - Comparison of the kinetics of glyburide and its active metabolites in humans.
AB  - The pharmacokinetics of glyburide (Gb) and its active metabolites, 4-trans
      hydroxyglibenclamide (M1) and 3-cis-hydroxyglibenclamide (M2), were compared in
      eight healthy subjects. After an overnight fast, each subject received a 3.5-mg
      single dose of Gb, M1 or M2 intravenously in random cross-over order. For
      comparison, a 3.5-mg oral dose of micronized formulation of Gb was also given in
      a test. The subjects continued to fast until standard meals were given at 0.5 and
      5.5 h after each dose. Serum samples and urine fractions were collected for 10 h.
      Serum concentrations of Gb, M1 and M2, and urine concentrations of M1 and M2 were
      determined by a selective and sensitive liquid chromatographic method. The two
      metabolites had very similar pharmacokinetic profiles, except for volume of
      distribution and renal clearance. Estimated mean volume of distribution, total
      and renal clearance of M1 and M2 were 20.8 +/- 8.4 litres, 11.9 +/- 1.7 litres/h,
      13.5 +/- 3.7 litres/h and 15.5 +/- 5.5 litres, 10.4 +/- 1.3 litres/h, 8.6 +/- 1.6
      litres/h, respectively. Estimates of the volume of distribution and total
      clearance were significantly higher than those of Gb, which were 7.44 +/- 1.53
      litres, 4.42 +/- 0.56 litres/h intravenously and 9.32 +/- 2.79 litres, 4.09 +/-
      0.45 litres/h orally. There was no significant difference in total metabolite
      urine recovery between intravenous or oral administration of Gb, suggesting
      almost complete oral bioavailability of the micronized glibenclamide formulation.

PMID- 8576297
TI  - Predictive performance of four pharmacokinetic methods for calculating digoxin
      dosage.
AB  - An evaluation was made of the performance of the Sheiner, Koup, Dobbs and Paulson
      methods for predicting total body clearance of digoxin in 59 patients with and
      without congestive heart failure (CHF). The predicted clearances were then used
      to predict the steady-state serum concentrations of digoxin. Actual serum
      concentrations were measured at steady state following single oral daily doses of
      digoxin for at least 1 month. Predictive performance was determined for each
      method by calculating the mean prediction error (ME) and the mean squared
      prediction error (MSE). Ninety-five per cent confidence intervals and correlation
      coefficients were also calculated. The prediction bias and precision of the
      methods were compared statistically by calculating the 95% confidence intervals
      of the delta ME and delta MSE. For patients with CHF, the Sheiner method was the
      least biased and the most precise for predicting observed serum levels. For
      patients without CHF, no significant difference between the Sheiner and Koup
      methods, and between the Dobbs and Paulson methods were seen, although the former
      two methods were less biased and more precise than the latter two. The Sheiner
      method was used as the basis for evaluating the performance of the three other
      methods in predicting digoxin clearance from patients with and without CHF. This
      revealed that the Koup, Dobbs and Paulson methods tended to overpredict
      clearances in patients with CHF; on the other hand, for patients without CHF, the
      Koup method was the least biased and the most precise of the three methods.

PMID- 8576298
TI  - Automated detection of digoxigenin-labelled B19 parvovirus amplicons by a capture
      hybridization assay.
AB  - An automated method to identify B19 amplicons, directly labelled with digoxigenin
      during amplification reaction was developed. The labelled amplicons were
      hybridized with a biotinylated B19 oligo-probe and captured on commercially
      available test tubes coated with streptavidin. The hybridized amplicons labelled
      with digoxigenin were detected using anti-digoxigenin Fab fragments conjugated to
      peroxidase and the colourimetric reaction automatically evaluated as an
      immunoenzymatic assay. Fifty serum samples were tested by the assay and the
      results were in accordance with those obtained by Southern blot analysis of
      amplified products. Due to the high sensitivity, specificity and reproducibility
      shown, the assay seems to be a practical and reliable test for the diagnosis of
      B19 infection and can be easily adapted to identify any digoxigenin-labelled
      amplified product of viral genomes.

PMID- 8576299
TI  - Comparison of conventional autoradiography with a new DNA enzyme immunoassay for
      the detection of hepatitis C virus-polymerase chain reaction amplification
      products.
AB  - The detection of HCV-PCR amplification products by DNA enzyme immunoassay (DEIA)
      was compared with conventional hybridization carried out with a 32P-labelled
      oligonucleotide probe. The detection limit of both methods was shown to be
      between 100 pg and 1 ng of amplicon. All serum samples of 40 HCV-seropositive
      patients were positive after PCR in autoradiography, but only 38 with the DEIA
      technique (sensitivity 95%). There were no false-positive reactions by either
      method. The advantage of the DEIA method was the fast and non-radioactive
      detection of HCV amplicons. DEIA combines the specificity of the hybridization
      event with the speed of an ELISA procedure and is suitable for HCV-PCR.

PMID- 8576300
TI  - Evaluation of 4 commercial test kits for parvovirus B19-specific IgM.
AB  - Four commercial test kits for parvovirus B19 IgM were evaluated by testing 491
      sera assembled into 7 panels. The serum panels were designed to assess
      sensitivity and specificity of the commercial assays and to reflect the various
      clinical settings in which acute B19 infection forms part of the differential
      diagnosis. A mu-capture radioimmunoassay (MACRIA) was used as the reference test.
      With respect to MACRIA, the commercial B19 IgM assays showed an overall
      sensitivity of 70.1-84.1% and specificity of 92.2 to 97.4%. Assay performance
      varied in different clinical situations. In sera from adults with acute B19
      arthropathy, all 4 assays were 100% sensitive, but in children with fifth
      disease, the sensitivity ranged from 44.1 to 88.6%. The sensitivity of all 4
      assays was also low when testing samples collected more than 6 weeks after onset
      of symptoms and in women with B19-associated embryopathy. Specificity was greater
      than 97% in healthy blood donors, but varied from 70.9 to 83.3% in patients
      acutely infected with other viruses, including rubella. Although the IgM test
      kits here evaluated may be usefully introduced for B19 diagnosis in certain
      settings, knowledge of their limitations will be important when results have been
      interpreted.

PMID- 8576301
TI  - Differential diagnosis of fish pathogenic rhabdoviruses by reverse transcriptase
      dependent polymerase chain reaction.
AB  - Reverse transcriptase-dependent polymerase chain reaction (RT-PCR) was applied to
      the detection and differentiation of viral hemorrhagic septicemia virus (VHSV)
      and infectious hematopoietic necrosis virus (IHNV) using primer pairs designed
      for the amplification of glycoprotein G-specific gene fragments of the two
      viruses. The products of 443 bp (VHS) and 548 bp (IHN), respectively, were
      amplified from the total RNA extracts of RTG-2 cells infected with a total of 9
      different strains of either VHS virus or IHN virus. Restriction analysis using
      FokI, and DNA sequencing of the PCR products demonstrated specificity of the
      amplification. The RT-PCR amplification of VHSV or IHNV G-genes was found to be a
      simple, highly specific and sensitive method allowing differential diagnosis of
      VHS and IHN within 8 h.

PMID- 8576302
TI  - Rapid differentiation of closely related isolates of two plant viruses by
      polymerase chain reaction and restriction fragment length polymorphism analysis.
AB  - Immunocapture reverse transcriptase-polymerase chain reaction (RT-PCR) followed
      by restriction fragment length polymorphism (RFLP) analysis of the product has
      been shown to be an effective procedure for discriminating serologically
      indistinguishable isolates of two plant viruses, raspberry bushy dwarf (RBDV) and
      zucchini yellow mosaic (ZYMV). For both viruses, only limited sequence
      information was available at the time of primer design, but most of the isolates
      which were tested could be amplified (the one exception being a serologically
      quite distinct isolate of ZYMV). Restriction endonucleases revealing diagnostic
      RFLPs were readily identified. Each of two isolates of ZYMV could be detected in
      the presence of the other and the relative proportions approximately quantified
      by visual estimation of the relative intensity of the appropriate bands. A range
      of isolates of different RBDV pathotypes were compared; isolates were grouped in
      ways that accorded with their known history. Computer analysis of the published
      sequence from which the primers had been derived showed the sequenced isolate to
      be identical with an isolate imported from the USSR. The PCR/RFLP procedure is
      rapid (it can be completed in less than 2 days), effective and will probably be
      generally applicable to distinguishing closely related virus isolates, even where
      little sequence information is available.

PMID- 8576303
TI  - Detection of potato leafroll virus in single aphids by the reverse transcription
      polymerase chain reaction and its potential epidemiological application.
AB  - A reverse transcription and polymerase chain reaction (RT-PCR) system was
      developed using two 20-mer primers located in the potato leafroll virus (PLRV)
      capsid gene. A 336-bp PCR product was detected from aphids (Myzus persicae) which
      had been fed on PLRV-infected plants. The PCR band was specific to PLRV as
      determined by Southern blots and detection by a PLRV-specific probe. As little as
      5 min exposure of aphids to PLRV-infected leaves resulted in the presence of PLRV
      specific bands in 13% of aphids. However, the percentage of PLRV-positive aphids
      increased with longer exposure to infected sources and reached 90% after 3-4 days
      of feeding. PLRV can be detected from a single viruliferous aphid or a single
      viruliferous aphid combined with up to 29 non-viruliferous aphids. PLRV can be
      detected from freshly collected aphids, those stored at -70 degrees C, or those
      stored in 70% ethanol at room temperature for extended periods. This method is
      applicable to assess the viruliferous nature of aphids caught in yellow-pan traps
      during the growing season or stored for over a year.

PMID- 8576304
TI  - Colorimetric microtiter plate hybridization assay using monoclonal antibody for
      detection of an amplified human immunodeficiency virus target.
AB  - Since detection of amplified polymerase chain reaction products is a complicated
      procedure, a colorimetric microtiter plate hybridization assay was developed to
      automate specific detection of amplified HIV targets. In this assay,
      hybridization is seen by an antibody reacting selectively with double-stranded
      DNA. One hundred and ten amplified products detected by a DNA enzyme immunoassay
      (DEIA) and by classical hybridization with a digoxigenin-labeling probe,
      detection sensitivities were less than 10 HIV targets per 10(6) cells. This study
      demonstrates the specificity and sensitivity of DEIA for detecting amplified HIV
      targets. The use of the same equipment as for ELISA and the complete automation
      of the procedure allow a large number of samples to be processed in the clinical
      laboratory.

PMID- 8576305
TI  - SYBR green I DNA staining increases the detection sensitivity of viruses by
      polymerase chain reaction.

PMID- 8576306
TI  - Monoclonal antibody blocking tests for the detection of HSV-1- and HSV-2-specific
      humoral responses: comparison with western blot assay.
AB  - Monoclonal antibody blocking radioimmunoassays (MAb block RIAs) which detect
      specific humoral responses to each of the two human herpes simplex virus (HSV)
      types are described. RIAs were compared with Western blot assay (WBA) in a blind
      study of 64 sera obtained from clinically well-documented cases of genital
      herpes. WBA and MAb block RIA each detected HSV-1 antibodies in 16/17 (94%) sera
      from confirmed HSV-1 genital infections (first episodes and recurrent
      infections). Detection of HSV-2 antibody in 21 sera from HSV-2 first episodes was
      more effective by WBA which identified homologous antibody in 19 (96%), whereas
      MAb block RIA detected HSV-2 antibody in 16 (76%). HSV-2 antibody was detected in
      24/25 (96%) sera from recurrent HSV-2 infections by WBA and by MAb block RIA, the
      highest degree of concordance for both methods. In addition, the MAb block RIA
      may be more effective in detecting the presence of HSV-1 antibody in sera from
      recurrent HSV-2 cases. Prevalence of HSV-1 and HSV-2 antibody was measured by the
      MAb block RIAs in 3 UK human study populations which consisted of 100
      children/young adolescents, 104 adult blood donors and 80 genito-urinary medicine
      clinic attenders.

PMID- 8576307
TI  - A simple imprint-hybridization method for detection of viroids.
AB  - An imprint-hybridization method has been designed to simplify the processing of
      samples during routine viroid indexing. The method requires minimal sample
      manipulation and has been evaluated for detection of viroids in 11 viroid-host
      combinations including 4 viroids (CEVd, CSVd, HSVd, ASBVd) and 7 hosts
      (chrysanthemum, citron, cucumber, Gynura, tomato, peach and avocado). The method
      is fast and sensitive, and provides additional information on the sites of viroid
      accumulation.

PMID- 8576308
TI  - Hepatitis E virus infection in acute hepatitis in Spain.
AB  - In order to study the prevalence of hepatitis E virus (HEV) infection in
      developed countries, IgG and IgM anti-HEV were determined in serum samples from
      382 patients with acute viral hepatitis (244 hepatitis A, 48 hepatitis B and/or
      D, and 90 non-A, non-B, non-C hepatitis), 76 healthy subjects, 55 hemophiliacs
      and 50 patients on hemodialysis. IgG anti-HEV antibodies were detected and
      confirmed by a synthetic peptide-based EIA in 5 (5.6%) non-A, non-B, non-C acute
      hepatitis, in 3 (6.5%) B and D acute hepatitis, in 10 (4%) acute A hepatitis, in
      3 (5.5%) of 54 healthy adults in none of the hemophiliacs and in 3 (6%) patients
      on hemodialysis. IgM anti-HEV antibodies were only detected in two cases of acute
      hepatitis B and/or D. Analysis of serial serum samples demonstrated IgG anti-HEV
      seroconversion in 3 of the 18 confirmed cases; one of them was also positive for
      IgM anti-HEV. All 3 acute anti-HEV-positive hepatitis cases occurred in adults,
      were community-acquired (two of them were intravenous drug addicts) and had a
      self-limited course. These results demonstrate that HEV is a minor cause of acute
      hepatitis in Spain. A similar low rate of IgG anti-HEV antibodies was detected in
      patients with different diseases, suggesting that HEV has a very low
      epidemiological impact. An apparent association of HEV infection with hepatitis B
      and D suggests a possible parenteral transmission of a mainly enteral pathogen.

PMID- 8576309
TI  - Synthesis and application of hepatitis E virus peptides to diagnosis.
AB  - Based on computer analysis of hydrophobicity and prediction of secondary
      structures for the full-length putative proteins encoded by open reading frame-1
      (ORF-1), ORF-2 and ORF-3 of hepatitis E virus (HEV), we selected antigenic
      regions with hydrophilicity, beta-turn, and beta-sheet, and synthesized 7
      peptides of possible epitope-containing regions of the polypeptide encoded by all
      3 ORFs of HEV genomic RNA by Merrifield's method of solid-phase synthesis. The
      synthetic peptides were screened and identified by solid-phase enzyme-linked
      immunosorbent assay (ELISA). Three of the peptides (EH174 from ORF-1, EH286 from
      ORF-2 and EH362 from ORF-3) showed antigenic activity and possible application
      for the development of anti-HEV test kits (the peptide-based ELISA). The
      laboratory experiments and clinical trials showed that the kits, using a set of 3
      synthetic HEV peptides as coating antigens, were of high specificity and
      exhibited good reproducibility. The small-scale seroepidemiological survey
      indicated high seroprevalence (14.3%) of anti-HEV in Tibetan populations.
      Additionally, the results also demonstrated good agreement with clinical
      findings, suggesting that the test kits will be of major use for immunodiagnosis
      and seroepidemiological surveys of HEV infection.

PMID- 8576310
TI  - A synthetic parvovirus B19 capsid protein can replace viral antigen in antibody
      capture enzyme immunoassays.
AB  - To establish a renewable source of parvovirus B19 antigens for diagnostic tests,
      gene sequences for the viral capsid proteins, VP1 and VP2, were cloned into
      baculovirus expression vectors and the recombinant viruses used to infect Sf9
      insect cells. Cell lysates examined by immunoblotting demonstrated reactive
      proteins corresponding to the expected sizes of native VP1 (83 kDa) and VP2 (58
      kDa). The VP2 protein was produced efficiently in quantity and self-assembled
      into empty capsids as shown by density equilibration in a CsCl step gradient. The
      VP2 protein was purified and used as an antigen in antibody-capture enzyme
      immunoassays for the detection of B19 IgG and IgM antibodies. Compared to a
      standard antibody-capture EIA based on whole viral antigen, the VP2-EIA gave a
      sensitivity of 100% and specificity of 97% in detection of B19 IgM in 138
      patients suspected of B19 infection. No IgM-positive specimens were missed. IgG
      detection yielded a sensitivity of 100% and specificity of 96% in the same
      population. Recombinant VP2 capsid proteins expressed in baculovirus-infected
      insect cells can substitute for serum-derived B19 virus in standard antibody
      capture EIA for the detection of B19 IgG and IgM with comparable results.

PMID- 8576311
TI  - Identification of Zucchini yellow mosaic potyvirus by RT-PCR and analysis of
      sequence variability.
AB  - A reverse transcription-polymerase chain reaction (RT-PCR) method was used to
      identify Zucchini yellow mosaic virus (ZYMV) in leaves of infected cucurbits.
      Oligonucleotide primers which annealed to regions in the nuclear inclusion body
      (NIb) and the coat protein (CP) genes, generated a 300-bp product from ZYMV and
      also from the closely related watermelon mosaic virus type 2 (WMV-2). However, no
      product was obtained from papaya ringspot potyvirus which also infects cucurbits.
      ZYMV and WMV-2 were differentiated using a third primer which was complementary
      to a sequence in the 3'-untranslated region; a 1186-bp amplified product was
      obtained for ZYMV only. Nucleotide sequence analysis of the 300-bp fragments of
      Australian ZYMV and WMV-2 strains revealed 93.7-100% sequence identity between
      ZYMV strains. Multiple sequence alignments indicated that the nucleotide sequence
      which codes for the N-terminus of the CP was 74-100% identical for different
      isolates of ZYMV. The Australian isolate of WMV-2 was 43-46% identical to all
      isolates of ZYMV and was 84.6% identical to a Florida isolate of WMV-2.

PMID- 8576312
TI  - Evaluation of the reliability of 6 current anti-HIV-1/HIV-2 enzyme immunoassays.
AB  - The sensitivity for early detection of HIV antibodies and specificity of 6 anti
      HIV-1/HIV-2 screening enzyme immunoassays (ELISAs) currently on the market were
      investigated by testing a panel of 249 well-characterized serum samples. The
      panel included sera from AIDS patients or children with congenital HIV infection,
      high-risk individuals and patients with conditions unrelated to AIDS. 'Tricky'
      sera (repeatedly positive results by ELISA and negative or indeterminate results
      by Western blot; n = 69) were also used in this evaluation along with 6
      seroconversion panels. One second-generation assay (Biotest) and two third
      generation assays (Abbott and Murex) showed the highest sensitivity for early
      detection of HIV-1 antibodies in seroconversion panels. A high specificity was
      achieved with the Cambridge Biotech (100%) and Ortho ELISA (99.4%). A relatively
      high rate of false-positive results was obtained with the Biotest (n = 10) and
      the Pasteur assays (n = 8) by testing 'tricky' sera and samples from high-risk
      individuals and from patients with other acute viral infections. In conclusion,
      it remains difficult to combine high specificity with an accurate detection of
      early seroconversion for anti-HIV-1/HIV-2 screening enzyme immunoassays.

PMID- 8576313
TI  - Role of nitric oxide in anaphylactic shock.
AB  - Nitric oxide, synthesized from the guanidino group of L-arginine by nitric oxide
      synthase, has an important role in pathophysiological changes associated with
      anaphylaxis. Nitric oxide production due to activation of constitutive nitric
      oxide synthase is detected using a nitric oxide-selective electrode in
      anaphylactic rabbits in vivo. A nitric oxide synthase inhibitor attenuates
      hypotension and hemoconcentration and decreases venous return but does not
      improve cardiac depression. Nitric oxide functionally antagonizes the effects of
      vasoconstrictors released by anaphylaxis in vitro. In animals pretreated with a
      nitric oxide synthase inhibitor, the cardiac output falls significantly, although
      venous return is increased. Pulmonary resistance is significantly increased with
      a nitric oxide synthase inhibitor, and L-arginine attenuates the bronchospasm.
      These findings suggest that production of nitric oxide may reduce the
      pathophysiologic changes, except for vasodilatation, associated with anaphylaxis.

PMID- 8576315
TI  - Segregation of pANCA antigenic recognition by DNase treatment of neutrophils:
      ulcerative colitis, type 1 autoimmune hepatitis, and primary sclerosing
      cholangitis.
AB  - Antineutrophil cytoplasmic antibodies (ANCA) have been identified in the serum of
      50-80% of ulcerative colitis (UC) patients. UC-associated ANCA yield a
      perinuclear staining pattern (pANCA) with alcohol-fixed neutrophils. More
      recently, pANCA have been detected in the serum of patients with primary
      sclerosing cholangitis (PSC) and other autoimmune liver diseases. Up to 70% of
      PSC patient sera and up to 92% of sera from patients with well-defined type 1
      autoimmune hepatitis (type 1 AIH) were found to express pANCA. Such expression by
      patients with PSC and type 1 AIH raises questions concerning the relationship of
      these pANCA to each other and to that of UC. Differences and similarities in
      pANCA characteristics are found among the three diseases, suggesting the use of
      pANCA to define specific disease subgroups. Our recent finding that the UC
      associated pANCA reactive antigen was localized within the nuclear domain
      prompted an examination of whether DNase treatment of neutrophils would alter
      antigenic recognition by the pANCA of UC, PSC, and type 1 AIH. While loss of
      antigenic recognition after DNase digestion of neutrophils was a dominant feature
      of the UC-associated pANCA, the majority of PSC and type 1 AIH pANCA recognized
      cytoplasmic constituents. These results further support the feasibility of
      defining and/or distinguishing disease subgroups based on the characterization of
      respective pANCA.

PMID- 8576314
TI  - CpG DNA: a pathogenic factor in systemic lupus erythematosus?
AB  - Systemic lupus erythematosus (SLE) is a multifactorial disease of unknown
      etiology. Characteristic features of SLE include (1) polyclonal B cell
      activation, (2) overexpression of the immune stimulatory cytokine interleukin-6
      (IL-6), (3) defective tolerance to self antigens, and (4) production of anti-DNA
      antibodies (Ab). Bacterial infection has been suspected as a triggering factor
      for lupus. Bacterial DNA differs from vertebrate DNA in the frequency and
      methylation of CpG dinucleotides. These CpG motifs in bacterial DNA induce a
      variety of immune effects, including (1) polyclonal activation of murine and
      human B cells, (2) IL-6 secretion, and (3) resistance to apoptosis, thereby
      potentially allowing the survival of autoreactive cells. These results suggest
      that microbial DNA could therefore be a pathogenic factor in SLE. SLE patients
      have elevated levels of circulating plasma DNA which is reportedly enriched in
      hypomethylated CpGs. Genomic DNA is also hypomethylated in SLE. The purpose of
      this review is to summarize the immune effects of CpG motifs and to present the
      evidence for their possible involvement in the pathogenesis of SLE.

PMID- 8576316
TI  - Expression of CD44 variants in human inflammatory synovitis.

PMID- 8576317
TI  - Inhibitory effect of the immunosuppressant FK506 on apoptotic cell death induced
      by HIV-1 gp120.
AB  - Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 may play
      a central role in inducing immunoregulatory disorders after HIV infection. The
      apoptotic death of normal human peripheral blood mononuclear cells was induced by
      priming with gp120 followed by stimulation with an anti-T cell receptor (TCR)
      antibody. Tumor necrosis factor-alpha produced by gp120-binding macrophages may
      be important to induce this cell death. Treatment of gp120-primed cells with an
      immunosuppressant (FK506) before TCR signaling inhibited apoptotic cell death,
      and this blocking effect of FK506 was concentration dependent. FK506 did not have
      any influence on cell growth and viability over the range of concentrations
      tested. These findings suggest that FK506 is a potentially useful drug in
      delaying the onset of AIDS after HIV infection.

PMID- 8576319
TI  - Evidence for IgG autoantibodies to galectin-3, a beta-galactoside-binding lectin
      (Mac-2, epsilon binding protein, or carbohydrate binding protein 35) in human
      serum.
AB  - Galectin-3 is a beta-galactoside-binding animal lectin formerly called epsilon
      protein, Mac-2, carbohydrate binding protein 35, CBH 30, L-29, or L34. The
      possible occurrence of autoantibodies to galectin-3 was investigated because
      crosslinking of galectins bound to IgE or Fc epsilon RI might produce mediator
      release from mast cells or basophils. Unexpectedly, a control serum from an
      individual free of current allergic symptoms was found to have a significantly
      elevated level of IgG anti-galectin-3 by ELISA employing galectin-3-coated wells
      incubated with test serum followed by HRPO-conjugated goat anti-human IgG. The
      reaction was not inhibitable by lactose, suggesting that it is not a result of
      binding of IgG by galectin-3 through lectin-carbohydrate interactions. The
      antibody activity was specifically adsorbed by galectin-3 and protein A
      conjugated Sepharose and was associated primarily with subclass IgG1. The
      presence of the antibodies was confirmed by immunoblotting showing binding of IgG
      to the 30-kD galectin-3 band. The relevant epitopes were in the galectin-3 N
      terminal domain. The propositus was subsequently found to have adenocarcinoma of
      the colon, and titers of IgG anti-galectin-3 were found to be sharply elevated
      after hemicolectomy. Similar antibody titers have not been found in family
      members, but small numbers of normal persons and patients with malignant
      neoplasms have been found to have evidence of IgG anti-galectin-3 antibodies at
      lower titers than the propositus. The pathogenesis of this autoimmune reaction is
      unclear, though there is a trend for it to occur in older persons.

PMID- 8576318
TI  - Immune deficiency following thermal trauma is associated with apoptotic cell
      death.
AB  - Thermal injury-associated specific immune deficiency occurs despite indicators of
      systemic activation of the lymphoid compartment. We investigated the possibility
      that postburn immune failure and T cell activation are casually related through
      activation-induced (apoptotic) cell death. The relationship between the cellular
      immune response and cell mortality was examined in cultures of peripheral blood
      mononuclear cells (PBMC) from 14 immunosuppressed patients with extensive burns
      (35-90% total body surface area). Impaired cellular immunity coincided with
      significantly reduced cell viability as ascertained by propidium iodide staining
      and dye reduction assays. Following stimulation with the mitogenic lectin,
      phytohemagglutinin (PHA), the majority of DNA in patient cultures was fragmented,
      suggesting the occurrence of apoptotic cell death. Even without stimulation a
      portion of patient cells was apoptotic as indicated by oligonucleosomal bands on
      agarose gel electrophoresis. Exogenous interleukin-2 or phorbol ester markedly
      reduced constitutive as well as PHA-induced DNA fragmentation. In situ
      demonstration of DNA strand breaks in freshly isolated patient PBMC, by a TdT
      based labeling technique, confirmed that a larger fraction (up to 60%) of
      circulating lymphocytes was undergoing apoptosis on the periphery. These novel
      observations suggest that apoptosis may play a major role in thermal injury
      related cellular immunodeficiency.

PMID- 8576320
TI  - CD4+ Th2 cell response cytokine production in bacterial meningitis.
AB  - There has been a growing body of evidence suggesting that CD4+ Th1/Th2 cell
      responses participate in pathologic and immunologic processes in infectious
      disease. Bacterial meningitis is a fatal disease of children and is associated
      with a spectrum of clinical syndromes. This study provides evidence of CD4+
      enhanced interleukin (IL)-4 and IL-6 but decreased IL-2 and interferon-gamma (IFN
      gamma) production, the induction of characteristic Th2 cell response cytokines in
      bacterial meningitis, which may play an important role in disease mechanism.
      Additionally, monocyte-induced enhanced IL-6, IL-8, and tumor necrosis factor
      alpha production may be associated with distinct clinical features such as fever,
      seizures, and neurological sequelae. A striking finding was also the highly
      deficient monocyte-induced granulocyte-macrophage colony-stimulating factor
      production. Of particular interest, the CD(8+)-enhanced IFN-gamma production may
      be required for the cytolytic activity or protective response to be maintained in
      this disease. Taken together, these data reveal that monocytes and CD4+ (Th2) and
      CD8+ subsets produce distinct cytokines in bacterial meningitis, which may exert
      an immunoregulatory and immunopathologic effect and thus mediate some of the
      clinical manifestations of the disease.

PMID- 8576321
TI  - Molecular localization of human IgG anti-F(ab')2 reactivity with variable- and
      constant-region lambda light-chain epitopes.
AB  - Human IgG antibodies reacting with antigenic determinants on F(ab')2 fragments
      represent generic antiidiotypic antibodies present in the serum of normal
      individuals. Additionally, the titers of these antibodies in the sera of patients
      with systemic lupus erythematosus (SLE) are inversely related to disease
      activity. Because these autoantibodies recognize predominantly light chain
      related epitopes, especially lambda type, we synthesized constant (C)lambda- and
      variable (V)lambda-related overlapping 7-mer peptides on polypropylene pins to
      determine anti-F(ab')2-reactive epitopes on human lambda light chains. ELISA
      reactivity of affinity-purified anti-F(ab')2 antibodies obtained from normal
      individuals and from patients with SLE, as well as murine anti-human light-chain
      monoclonal antibodies specific for C lambda and V lambda subgroup-related
      determinants, was tested using the overlapping 7-mers of human lambda light-chain
      sequence. The patterns of reactivity against C lambda-related peptides were
      similar in both normal and SLE-derived anti-F(ab')2 antibodies. However,
      reactivity profiles against V lambda-related peptides were distinctively
      different between the normal and the SLE-associated anti-F(ab')2 autoantibodies.
      A decrease in reactivity among the SLE IgG anti-F(ab')2 antibodies was noted for
      particular amino acid V lambda complementarity-determining region (CDR) residues,
      including glycine at positions 27 and 54, alanine at 16 and 37, and tyrosine at
      28 and 91. This different pattern of reactivity from normal may indicate that in
      SLE there is a failure of antiidiotypic control mechanisms, as reflected by a
      defect in production of antibody to immunodominant V lambda CDR residues.

PMID- 8576322
TI  - Natural autoantibodies in sera of patients with Gaucher's disease.
AB  - Gaucher's disease (GD) is associated with hyperactivity of the immune system,
      which manifests by polyclonal hypergamma-globulinemia and an increased incidence
      of monoclonal gammopathies in GD patients. We analyzed sera of 43 patients with
      GD for the presence of autoantibodies against 14 autoantigens. The results
      demonstrated a significant increase in the incidence of all autoantibodies
      tested, ranging from 11% for anti-RNP, pyruvate dehydrogenase (PDH), and DNA
      antibodies to 57% for rheumatoid factor. The autoantibodies were of all three
      isotypes, namely, IgG, IgM, and IgA. There was no correlation between the levels
      of immunoglobulins in the serum and the titer of autoantibodies found.
      Immunization of naive mice with a pool of purified anti-DNA antibodies form GD
      patients did not result in induction of experimental systemic lupus erythematosus
      (SLE), suggesting that they may represent natural autoantibodies that are not
      pathogenic. In conclusion, we found high titers of natural, polyspecific,
      nonpathogenic autoantibodies in the sera of GD patients.

PMID- 8576324
TI  - Biochemical fingerprinting compared with ribotyping and pulsed-field gel
      electrophoresis of DNA for epidemiological typing of enterococci.
AB  - The Phene Plate (PhP) biochemical fingerprinting system for bacteria is based on
      measurements of the kinetics of bacterial biochemical reactions. This system was
      modified for typing of enterococci and was compared with DNA typing by pulsed
      field gel electrophoresis and with ribotyping by using 45 Enterococcus faecalis
      isolates from international collections. It was also used to study 170 fecal
      enterococcal isolates from healthy individuals and 28 isolates of E. faecalis
      from the blood of neonates. The PhP system showed a high degree of discriminatory
      power for unrelated enterococcal isolates. Among the 170 unrelated fecal
      isolates, 107 isolates from international collections, PhP typing discriminated
      19 types, and ribotyping discriminated 5 types. In most cases, when isolates were
      of the same DNA type, they were also of the same PhP type, and the level of
      agreement between these two methods was high (96%). A combination of PhP typing
      and DNA typing identified 34 different types, but ribotyping did not yield any
      further discrimination. PhP typing of E. faecalis isolates from healthy
      individuals (n = 89) and from the blood of neonates with septicemia (n = 28)
      yielded a diversity of 0.93 for both populations and similar major PhP types in
      both populations. Thus, the isolates from blood seemed to consist of a normal E.
      faecalis population, without a dominance of certain strains associated with
      virulence. We conclude that the PhP system is useful for epidemiological studies
      of enterococcal isolates, yielding results similar to those obtained with DNA
      typing by pulsed-field gel electrophoresis. Since PhP typing is a method that is
      simple and rapid and that is based on automatic evaluation of the data, it is
      suitable for analyzing large numbers of isolates and can be used alone or in
      combination with DNA typing or epidemiological and ecological studies of
      enterococci.

PMID- 8576323
TI  - Mycobacterium conspicuum sp. nov., a new species isolated from patients with
      disseminated infections.
AB  - A new type of slowly growing, nonphotochromogenic mycobacterium was recovered
      from two patients with disseminated disease. The growth characteristics, acid
      fastness, acids were consistent with those for Mycobacterium species. The results
      of biochemical investigations, lipid analyses, and comparative 16S rRNA
      sequencing showed that these isolates represent a new slowly growing
      Mycobacterium species which is named Mycobacterium conspicuum.

PMID- 8576325
TI  - Genetic relatedness of Cryptococcus neoformans clinical isolates grouped with the
      repetitive DNA probe CNRE-1.
AB  - Cryptococcus neoformans isolates from eight patients with cryptococcal infection
      were previously assigned into three groups on the basis of repetitive DNA probe
      (CNRE-1) restriction fragment length polymorphisms. These groups accounted for a
      disproportionate number of recent clinical isolates in New York City. To further
      examine the genetic relatedness of isolates within and across CNRE-1 groups, the
      DNA sequence of the 779-base URA5 gene from each strain was amplified and
      sequenced. The number of nucleotide differences occurred in the third codon
      position or in introns. Pairwise comparisons revealed average nucleotide
      differences within a CNRE-1 group of 4.8 +/- 2.6 (n = 8) and between CNRE-1
      groups of 21.9 +/- 7.0 (n =20) (P <0.001) Analysis of URA5 sequences defined
      three groups that were congruent with those defined by CNRE-1 restriction
      fragment length polymorphisms. PCR amplification of an rDNA intergenic spacer
      revealed conservation of the intergenic spacer length within groups.
      Electrophoretic karyotyping did not distinguish between two isolates in each of
      two CNRE-1 groups. DNA from all isolates studied hybridized to an alpha mating
      type-specific probe. We interpret these results as suggesting a clonal population
      structure for some pathogenic isolates of C. neoformans in New York City.

PMID- 8576326
TI  - Isolation of Mycoplasma pneumoniae from the human urogenital tract.
AB  - Mycoplasma pneumoniae is a common etiologic agent of lower respiratory tract
      infections in humans. However, it has been reported previously that the organism
      has occasionally been isolated from sites other than the oropharynx and
      respiratory tract. We report the isolation of 24 strains of M. pneumoniae from
      urogenital specimens obtained from 22 female patients. Most isolates were of
      cervical origin from patients attending several local gynecological clinics over
      a 2-year period. Strains were also isolated from the urethra of one of three
      healthy male sexual partners of female patients positive for the organism. Single
      serum specimens obtained from three female patients and three different male
      sexual partners showed antibody levels suggestive of either recent respiratory
      infection or genital tract colonization with M. pneumoniae. Although there is no
      apparent definitive explanation for the localized outbreak of the organism at
      these unusual sites, the possible transfer through sexual and/or orogenital
      contact remains the most likely mode of transmission. The occurrence of an
      organism with obvious pathogenicity for human epithelial tissue in the urogenital
      tract suggests such transfer could play a role in genital tract infection.

PMID- 8576327
TI  - Identification and characterization of an immunogenic outer membrane protein of
      Campylobacter jejuni.
AB  - We cloned and expressed in Escherichia coli a gene encoding an 18-kDa outer
      membrane protein (Omp18) from Campylobacter jejuni ATCC 29428. The nucleotide
      sequence of the gene encoding Omp18 was determined, and an open reading frame of
      165 amino acids was revealed. The amino acid sequence had the typical features of
      a leader sequence and a signal peptidase II cleavage site at the N-terminal part
      of Omp18. Moreover, the sequence had a high degree of similarity to the
      peptidoglycan-associated outer membrane lipoprotein P6 of Haemophilus influenzae
      and the peptidoglycan-associated lipoprotein PAL of E. coli. Southern blot
      analysis in which the cloned gene was used as a probe revealed genes similar to
      that encoding Omp18 in all species of the thermophilic group of campylobacters as
      well as Campylobacter sputorum. All campylobacters tested expressed a protein
      with a molecular mass identical to that of Omp18. The protein reacted
      immunologically with polyclonal antibodies directed against Omp18 from C. jejuni.
      PCR amplification of the gene encoding Omp18 with specific primers and subsequent
      restriction enzyme analysis of the amplified DNA fragments showed that the gene
      for Omp18 is highly conserved in C. jejuni strains isolated from humans, dogs,
      cats, calves, and chickens but is different in other Campylobacter species. In
      order to obtain pure recombinant Omp18 protein for serological assays, the cloned
      gene for Omp18 was genetically modified by replacing the signal sequence with a
      DNA segment encoding six adjacent histidine residues. Expression of this
      construct in E. coli allowed purification of the modified protein (Omp18-6xHis)
      by metal chelation chromatography. Sera from patients with past C. jejuni
      infection reacted positively with Omp18-6xHis, while sera from healthy blood
      donors showed no reaction with this antigen. Omp18, which is an outer membrane
      protein belonging to the family of PALs is well conserved in C. jejuni and is
      highly immunogenic. It is therefore a good candidate as an antigen for the
      serological diagnosis of past C. jejuni infections.

PMID- 8576328
TI  - Molecular epidemiology of toxigenic Vibrio cholerae in Bangladesh studied by
      numerical analysis of rRNA gene restriction patterns.
AB  - Cholera is endemic in Bangladesh, and a regular seasonal pattern of cholera
      epidemics occurs. We examined the clonal relationships among 103 clinical and
      environmental Vibrio cholerae isolates belonging to O1, O139, or non-O1 non-O139
      serogroups isolated during epidemic and interepidemic periods in Bangladesh and
      compared them with those of 51 V. cholerae isolates from four countries in Asia
      and Africa. These studies were done by a computer-assisted numerical analysis of
      the restriction endonuclease cleavage patterns of rRNA genes (ribotypes).
      Unweighed pair-group cluster analysis of BglI- and HindIII-generated band
      patterns revealed 16 clusters. Ribotypes were defined as clusters of strains
      possessing > 98% similarity. The results showed that 154 isolates could be
      differentiated into 15 different ribotypes, and strains belonging to 3 of these
      ribotypes (ribotypes I, V, and VIIIA and VIIIB) were isolated more frequently
      during the epidemic periods than during interepidemic periods in Bangladesh.
      Classical vibrios belonged to six different ribotypes (ribotypes I to VI), with a
      mean similarity coefficient of 0.84, and the El Tor vibrios belonged to five
      different ribotypes (ribotypes VIIIA and IX to XII), with a mean similarity
      coefficient of 0.82. A single clone of El Tor vibrios (ribotype XII) was resident
      in Tanzania, whereas Nigeria, Syria, and India shared toxigenic El Tor strains
      with Bangladesh. Cholera toxin (CT)-positive O139 vibrios isolated from
      Bangladesh and India belonged to a single ribotype (ribotype VIIIB) and were >
      98% similar to one of the ribotypes of El Tor vibrios (ribotype VIIIA), but a CT
      negative O139 vibrio from Argentina (ribotype XIII) was < 75% similar to the same
      cluster of El Tor vibrios, thus suggesting more than one possible origin for O139
      vibrios. Strains belonging to the same ribotypes (ribotypes VIII to X) were
      isolated from both patients and surface water in Bangladesh, indicating possible
      transmission through surface water. A clone of a CT-positive environmental
      isolate of non-O1 V. cholerae (ribotype VII) was found to be closely related
      (76.3% similarity) to a clone of classical vibrios (ribotype I) and was only
      between 27.2 and 56.1% similar to clusters of El Tor, O139, and two other non-O1
      nontoxigenic clones.

PMID- 8576329
TI  - Evaluation of Sanofi Diagnostics Pasteur Chlamydia Microplate EIA shortened assay
      and comparison with cell culture and Syva Chlamydia MicroTrak II EIA in high- and
      low-risk populations.
AB  - Seven hundred thirty-two female urogenital samples were collected for Chlamydia
      trachomatis testing by both the Sanofi Diagnostics Pasteur (Chaska, Minn.)
      Chlamydia Microplate EIA by the shortened protocol and the Syva (San Jose,
      Calif.) MicroTrak II EIA, and the results were compared with those obtained by
      cell culture. For the analysis of samples from female patients, the patients were
      divided into high- and low-risk categories. An additional 121 male urethral
      samples were collected and tested by the Sanofi Microplate EIA and cell culture;
      for the analysis of samples from male patients, the patients were divided into
      asymptomatic and symptomatic categories. All specimens positive by enzyme
      immunoassay (EIA) were confirmed by a blocking assay following the respective
      manufacturer's instructions. Specimens negative by EIA that fell within a gray
      zone 30% below the cutoff and negative cultures with one or more corresponding
      positive EIA results were tested further by cytocentrifugation and direct
      immunofluorescent assay. The overall sensitivity, specificity, positive
      predictive value, and negative predictive value for Syva versus culture were 94,
      98.8, 85.5 and 99.6%, respectively. After resolution, the results were 94.5,
      99.6, 94.5, and 99.6%, respectively. The parallel results for the Sanofi
      Microplate EIA versus culture were 94.0, 98.7, and 83.9, and 99.6%, respectively,
      and after being resolved, the results were 94.9, 100, 100, and 99.6%,
      respectively. In the small male population tested, the resolved results of the
      Sanofi Microplate EIA versus culture demonstrated sensitivity, specificity,
      positive predictive value, and negative predictive value of 100, 100, 100, and
      100%, respectively. The present study demonstrated that the Sanofi Microplate EIA
      shortened protocol is highly sensitive and specific in comparison with cell
      culture and the Syva MicroTrak II EIA.

PMID- 8576330
TI  - Vancomycin-resistant enterococci colonizing the intestinal tracts of hospitalized
      patients.
AB  - A point prevalence culture survey was carried out to investigate the prevalence
      of fecal carriage of vancomycin-resistant enterococci (VRE) among patients
      admitted to an 800-bed general hospital where no VRE had been isolated
      previously. Twenty-two of 636 patients (3.5%) were found to be VRE carriers.
      Eighteen strains were identified as Enterococcus faecium, three were identified
      as Enterococcus gallinarum, and one was identified as Enterococcus faecalis. The
      susceptibilities of the enterococci to ampicillin, vancomycin, and teicoplanin
      were determined by the disk diffusion and the agar dilution methods. High-level
      resistance (HLR) to gentamicin and streptomycin was determined by the agar
      screening method. Eighteen strains (82%) were highly resistant to vancomycin, and
      four strains (18%) were moderately resistant to vancomycin. Five strains were
      susceptible to teicoplanin (23%; MICs, < or = 8 micrograms/ml). Only one strain
      (4.5%, E. faecium) showed HLR to gentamicin, and six strains (27%) showed HLR to
      streptomycin (one E. faecalis and five E. faecium strains). All 18 E. faecium and
      1 E. faecalis strain carried the vanA gene, and 3 E. gallinarum strains carried
      the vanC gene. An epidemiological investigation revealed several risk factors for
      VRE colonization: hospitalization and duration of stay in the hematology
      department and prior vancomycin treatment. The study demonstrates that the
      patient's gastrointestinal tract is a possible reservoir for VRE, even in
      hospitals where VRE infections have not yet been observed. Therefore, we conclude
      that infection control precautions and restriction of glycopeptide usage may be
      key issues in limiting the emergence and spread of nosocomial VRE infections.

PMID- 8576331
TI  - PCR and direct fluorescent-antibody staining confirm Chlamydia trachomatis
      antigens in swabs and urine below the detection threshold of Chlamydiazyme enzyme
      immunoassay.
AB  - In order to test the hypothesis that specimens blocking with a neutralizing
      reagent below the cutoff of the Chlamydiazyme enzyme immunoassay represent
      infected patients, we used direct fluorescent-antibody staining for elementary
      bodies (EBs) and PCR to confirm results for cervical swabs collected from 55,963
      women and urethral swabs or first-void urine (FVU) samples collected from 5,781
      men attending physicians' offices in the Toronto, Canada, area. Within a grey
      zone arbitrarily selected to represent values up to 40% below the positive
      threshold of the test run, 134 cervical swabs, 44 urethral swabs, and 39 FVU
      specimens exhibited a blocking response ( > 50% reduction in signal). Three or
      more EBs were observed in each of 98 cervical swabs (73.1%), 38 urethral swabs
      (86.4%), and 21 FVU specimens (53.8%). Of the 36 cervical swabs with fewer than
      three EBs, 33 were PCR positive; the positive PCR results for male specimens were
      6 of 6 urethral swabs and 17 of 18 FVU samples. Application of the blocking test
      to specimens negative in the Chlamydiazyme enzyme immunoassay but having optical
      densities within 40% of the cutoff added 14.2% (217 of 1,531 specimens) more
      positive results to the survey. A total of 213 of 217 samples (98.2%) were
      reconfirmed as having EBs or DNA.

PMID- 8576332
TI  - Molecular subtyping of prevalent M serotypes of Streptococcus pyogenes causing
      invasive disease.
AB  - Reproducible methodologies and a scheme for high-resolution genotyping of
      Streptococcus pyogenes were defined with respect to a study of six predominant M
      serotypes causing invasive group A streptococcal disease in the United Kingdom.
      Serotype reference strains were compared with nine clinical isolates of each
      serotype from patients with diseases such as pneumonia, puerperal sepsis, toxic
      shock-like-syndrome, cellulitis, or necrotizing fasciitis. Four enzymes were
      evaluated for their discriminatory power in 16S rRNA gene-specific ribotyping.
      Discriminatory power was greatest with EcoRI, which generated serotype-specific
      ribotypes, and with SacI, which could subdivide strains of the same M serotype.
      Twenty-five combined ribotypes were found among the 60 strains, and the indices
      of discriminatory power (D values) of this method varied from 0.51 within
      serotype M1 to 0.98 within strains of serotype M5. Macrorestriction with the
      rarely cutting endonuclease SmaI and pulsed-field gel electrophoresis gave D
      values varying from 0.37 within serotype M1 to the maximal 1.0 within serotype
      M5. Comparison of macrorestriction profiles revealed various degrees of genetic
      heterogeneity within M serotypes. Strains of M1, M3, M6, and M11 exhibited
      clonally related macrorestriction profiles, while those of R28 and M5 strains
      were consistent with polyphyletic origin.

PMID- 8576333
TI  - Controlled clinical evaluation of BACTEC Plus Aerobic/F and BacT/Alert Aerobic
      FAN bottles for detection of bloodstream infections.
AB  - A total of 7,190 blood culture sets were obtained from adult patients with a
      suspected bloodstream infection. A 20-ml sample of blood was distributed equally
      between the aerobic FAN bottle which was monitored in the BacT/Alert system and a
      Plus Aerobic/F bottle which was monitored in the BACTEC 9240 system. A total of
      988 positive cultures were obtained from 483 patients; however, only 453 positive
      cultures from 173 patients met the criteria for volume ( > or = ml per bottle)
      and clinical significance on the basis of concurrent case review required for
      data analysis. There were 25 and 68 false positives from the FAN and Plus
      Aerobic/F bottles, respectively. There were no statistically significant
      differences between systems in the number of positive cultures or septic episodes
      by species; however, the total number of Enterobacteriaceae and Pseudomonas
      aeruginosa isolates combined was significantly greater in the FAN bottle (P =
      0.04). Detection times did not differ significantly between systems for positive
      cultures; however, episodes of Staphylococcus aureus bacteremia were detected
      significantly more rapidly from the FAN bottle (P = 0.005). There was no
      significant difference between systems in the detection of bloodstream infections
      in patients receiving antibiotics at the time of blood culture.

PMID- 8576334
TI  - Detection of newly recognized rodent parvoviruses by PCR.
AB  - Several autonomous parvovirus isolates distinct from the prototypic rodent
      parvoviruses have recently been identified. These include variants of a mouse
      orphan parvovirus (MOPV) and a hamster isolate designated hamster orphan
      parvovirus (HOPV). In this study, a PCR primer set specific for these newly
      identified rodent parvoviruses was designed on the basis of DNA sequence
      comparisons of these isolates with other autonomous parvoviruses. The specificity
      of the primer set was determined by testing viral preparations of seven different
      parvoviruses and eight other viruses known to infect rodents. The PCR assay
      amplified the expected 260-bp product only in the presence of DNA from MOPV,
      HOPV, or LuIII a parvovirus of unknown species origin. The assay was able to
      detect as little as 10 pg of MOPV viral DNA or 1 pg of HOPV viral DNA, and it was
      able to detect MOPV in tissues from naturally infected mice and HOPV in tissues
      from experimentally infected hamsters. In contrast, the 260-bp product was not
      amplified from tissues of MOPV-negative mice or mock-infected hamsters. Our
      findings indicate that this PCR assay provides a rapid, specific, and sensitive
      method for the detection of MOPV in mice, HOPV in hamsters, and MOPV and HOPV in
      cell culture systems and that it may also be useful for the detection of LuIII
      contamination of cell culture systems.

PMID- 8576335
TI  - Specific detection of methicillin-resistant Staphylococcus species by multiplex
      PCR.
AB  - In Staphylococcus aureus, mecA and femA are the genetic determinants of
      methicillin resistance. By using a multiplex PCR strategy, 310- and 686-bp
      regions of the mecA and femA genes, respectively, were coamplified to identify
      susceptible (lacking mecA) and resistant (mecA+) staphylococci and to
      differentiate S. aureus (femA+) from coagulase-negative staphylococci (lacking
      femA). A third staphylococcal genomic sequence, corresponding to IS431 and
      spanning 444 bp, was used as a PCR control. One hundred sixty-five staphylococcal
      strains were tested. All 72 methicillin-resistant strains were found to be mecA+,
      and 92 of the 93 susceptible isolates lacked mecA. Only one coagulase-negative
      Staphylococcus isolate carrying the mecA gene was highly susceptible to
      oxacillin. The femA determinant was a unique feature of S. aureus; it was found
      in 100% of the S. aureus strains tested but was undetectable in all of the
      coagulase-negative staphylococci tested. The possibility of directly detecting
      the mecA and femA genes in blood samples was also investigated. After two
      amplification steps, a sensitivity of 50 microorganisms per ml of freshly
      collected spiked blood was achieved. In conclusion, coamplification of mecA and
      femA determinants proved to be very reliable both for rapid detection of
      methicillin resistance and differential diagnosis between S. aureus and other
      staphylococci. This technique, which can be successfully performed with blood
      samples, could be a useful tool in the diagnosis and treatment monitoring of
      staphylococcal infections.

PMID- 8576336
TI  - Evaluation and validation of a monoclonal immunofluorescent reagent for direct
      detection of Bordetella pertussis.
AB  - An outbreak of pertussis in Manitoba, Canada, provided an opportunity to evaluate
      the recently developed monoclonal antibody (MAb) BL-5 for the direct detection of
      Bordetella pertussis. The MAb recognizes a lipooligosaccharide epitope. A total
      of 1,507 consecutive nasopharyngeal swabs for culture and companion smears for
      direct fluorescent-antibody (DFA) detection were evaluated at Cadham Provincial
      Laboratory between September and November 1994. The cutoff for DFA positivity was
      four fluorescing organisms with morphology characteristic of B. pertussis. PCR
      analysis for B. pertussis DNA was performed on a subset of 100 smears by eluting
      material from the slides after DFA examination. In comparison with culture, the
      sensitivity, specificity, and positive and negative predictive values of BL-5
      were 65.1% (41 of 63 samples), 99.6% (1,438 of 1,444 samples), 87.2% (41 of 47
      samples), and 98.5% (1,438 of 1,460 samples), respectively. The sensitivity of
      culture compared with PCR was 45.5% (10 of 22 samples) for the subset of 100
      specimens tested by both procedures. An expanded "gold standard" of positivity by
      culture or PCR for these 100 specimens resulted in DFA sensitivity, specificity,
      and positive and negative predictive values of 32.3, 97.1, 83.3, and 76.1%,
      respectively. The utility of MAb BL-5 for direct detection of B. pertussis in a
      clinical laboratory setting has been demonstrated by this investigation.

PMID- 8576337
TI  - Comparison of Legionella pneumophila isolates by arbitrarily primed PCR and
      pulsed-field gel electrophoresis: analysis from seven epidemic investigations.
AB  - Arbitrarily primed PCR (AP-PCR) and pulsed-field gel electrophoresis (PFGE)
      subtyping were applied to clinical and environmental isolates from seven
      unrelated outbreaks of Legionnaires' disease. The patterns observed with each
      method matched patient isolates and the epidemiologically linked source of
      disease for each of the seven outbreaks. PFGE allowed more discrimination among
      various isolates, although AP-PCR usually gave comparable results. With both
      methods, certain patterns appeared to predominate in the comparison of the seven
      outbreaks. Of five clinical isolates not associated with the outbreaks, three
      gave profiles distinct from those observed in the outbreaks by both methods. This
      suggests that there are at least two predominant subtypes of Legionella
      pneumophila serogroup 1 associated with outbreaks. Investigations of outbreaks of
      legionellosis should employ either PFGE or AP-PCR in addition to monoclonal
      antibody analysis.

PMID- 8576338
TI  - Characterization of ear fluid isolates of Alloiococcus otitidis from patients
      with recurrent otitis media.
AB  - Nineteen isolates of Alloiococcus otitidis from ear fluid samples collected by
      tympanostomy from patients at four geographic locations were identified by
      phenotypic characterization and genetic relatedness. Initial growth of A.
      otitidis isolates occurred after 3 days at 37 degrees C on brain heart infusion
      (BHI) agar with 5% rabbit blood. Heavy growth occurred in BHI broth supplemented
      with 0.07% lecithin and 0.5% Tween 80 after 4 days of incubation. The isolates
      were gram-positive cocci that divided on an irregular plane and produced
      metabolic lactic acid, pyrrolidonyl arylamidase, and leucine aminopeptidase.
      These cocci grew sparsely in 6.5% NaCl-BHI broth, were asaccharolytic on both
      fermentative and oxidative bases, and were cytochrome negative by the iron
      porphyrin test. The cellular fatty acid profile of A. otitidis was distinguished
      from those of related genera and characterized by major amounts ( > or = 14%) of
      16:0, 18:2, 18:1 omega 9c, and 18:0 and smaller amounts of 14:0, 16:1 omega 7c,
      17:0, and 18:1 omega 7c. Fifteen isolates demonstrated > 69% relatedness by DNA
      DNA hybridization. Four isolates plus the original 15 were confirmed as A.
      otitidis by dot blot hybridization with a digoxigenin-labeled nucleotide probe
      specific for this species. The intergenic space between the genes coding for the
      16S and 23S rRNAs of alloiococci was amplified by PCR, analyzed by restriction
      fragment length polymorphism, and determined to consist of three different
      genetic types. Although beta-lactamase negative, A. otitidis demonstrated
      intermediate levels of resistance to beta-lactams, including expanded-spectrum
      cephalosporins, and were resistant to trimethoprim-sulfamethoxazole and
      erythromycin.

PMID- 8576339
TI  - Use of PCR for prenatal and postnatal diagnosis of congenital rubella.
AB  - A reverse transcription-nested PCR assay (RT-PCR) was evaluated for diagnosis of
      congenitally acquired rubella in utero and during infancy. RT-PCR was compared
      with virus isolation for retrospective detection of rubella virus in placental
      and fetal tissues obtained after termination of pregnancy following primary
      rubella or rubella virus reinfection. Concordant results were obtained for 85% of
      samples; rubella virus RNA was detected by RT-PCR alone in four samples, and
      rubella virus was detected by isolation alone in two samples. Samples were also
      obtained for prenatal diagnosis of congenital infection; rubella virus RNA was
      detected in three of seven chorionic villus samples and one of three amniotic
      fluid samples by RT-PCR, while rubella virus was isolated in only one chorionic
      villus sample. To demonstrate that the RNA extracted from chorionic villus
      samples contained amplifiable RNA, a nested RT-PCR was used to detect keratin
      mRNA. Rubella virus was detected in placenta in two cases in which the fetus was
      uninfected, and there was no evidence of rubella virus in the placenta from one
      case in which the fetus was infected. Thus, detection of rubella virus in
      chorionic villus samples by RT-PCR may not always correctly predict fetal rubella
      virus infection. RT-PCR was successfully used for the diagnosis of congenitally
      acquired rubella in infancy. Rubella virus RNA was detected in cyropreserved or
      formalin-fixed lens aspirates obtained from infants in India with serologically
      confirmed congenital rubella but not in samples from controls with inherited
      cataract.

PMID- 8576340
TI  - Combined PCR-oligonucleotide ligation assay for rapid detection of Salmonella
      serovars.
AB  - We have developed a rapid and sensitive assay for the detection of Salmonella
      serovars in veterinary clinical specimens. This method utilizes a short
      cultivation period followed by PCR. For detection of the amplified product, an
      enzyme-linked immunosorbent assay (ELISA)-based oligonucleotide ligation assay
      (OLA) was used. In this study, the PCR-OLA technique was compared with
      conventional culture and membrane hybridization for the detection of Salmonella
      bacteria. In evaluating the PCR-OLA with Salmonella serovars and non-Salmonella
      strains of bacteria, A490 readings for 51 Salmonella strains, representing 28
      serovars, were significantly higher (P < 0.05) than those for 25 non-Salmonella
      bacteria. With serial 10-fold dilutions of Salmonella CFU or with known
      concentrations of purified chromosomal DNA from Salmonella typhimurium ATCC
      29946, the PCR-OLA was able to detect > or = 20 CFU per assay or > or = 80 fg of
      chromosomal DNA (corresponding to 160 molecules of DNA). Of 102 suspect clinical
      specimens screened, 15 were positive for Salmonella bacteria by both culture and
      the PCR-OLA procedure (100% sensitivity), and 3 samples were positive only by PCR
      OLA (96.6% specificity), indicating a positive predictive value of 83.3% and a
      negative predictive value of 100%. In all experiments, the PCR-OLA was as
      sensitive as membrane hybridization. These results indicate that a limited
      enrichment cultivation and PCR-OLA could be used as a presumptive screening test
      for the detection of Salmonella serovars from any sample that currently requires
      extensive cultivation and that this assay would be adaptable to automation.

PMID- 8576341
TI  - Escherichia coli O157:H7 restriction pattern recognition by artificial neural
      network.
AB  - An artificial neural network model for the recognition of Escherichia coli
      O157:H7 restriction patterns was designed. In the training phase, images of two
      classes of E. coli isolates (O157:H7 and non-O157:H7) were digitized and
      transmitted to the neural network. The system was then tested for recognition of
      images not included in the training set. Promising results were achieved with the
      designed network configuration, providing a basis for further study. This
      application of a new generation of computation technology serves as an example of
      its usefulness in microbiology.

PMID- 8576342
TI  - Performance of a rapid, on-site human immunodeficiency virus antibody assay in a
      public health setting.
AB  - Rapid, on-site human immunodeficiency virus (HIV) testing has the potential to
      improve the delivery of prevention services in publicly funded counseling and
      testing sites. The Single Use Diagnostic System (SUDS) HIV-1 is the only rapid
      enzyme immunoassay (EIA) approved for diagnostic use in the United States. To
      evaluate the feasibility of using SUDS in public clinics and to validate the
      test's performance in a public health laboratory, we conducted blinded SUDS
      testing on plasma sent for HIV testing. From 19 March through 30 June 1993, 1,923
      consecutive samples from a sexually transmitted diseases clinic and an HIV
      counseling and testing clinic were tested on site with SUDS. Tests done in the
      first two weeks with a malfunctioning centrifuge n = 402) and those done when
      there were excessively high temperatures in the laboratory (n = 53) were analyzed
      separately. Of 1,466 tests, 39 were positive by both SUDS and EIA (with Western
      blot [immunoblot] confirmation) and 7 were SUDS positive and EIA negative.
      Western blotting was used as the "gold standard" to adjudicate these
      discrepancies. There were no SUDS-negative and EIA-positive tests. Compared with
      that of EIA (with Western blot confirmation), the sensitivity of SUDS was 100%
      (95% confidence interval, 88.8 to 100%) and the specificity was 99.5% (95%
      confidence interval, 98.9 to 99.8%). The positive predictive value of SUDS was
      88% in the STD clinic and 81% in the HIV counseling and testing clinic. There was
      a 7.7-fold increase in false positives, from 0.48 to 3.7%, when there was
      inadequate centrifugation and when the temperature exceeded the manufacturer's
      recommendations. Rapid, on-site HIV testing by the SUDS assay is feasible and
      practical in public health settings. The test can be performed accurately, at
      reasonable cost, and within the time frame of a typical clinic visit. Caution
      should be used, however, as two conditions adversely affected the accuracy of
      this test: inadequate specimen preparation and elevated temperature.

PMID- 8576343
TI  - Analysis of Enterococcus faecalis isolates from intercontinental sources by
      multilocus enzyme electrophoresis and pulsed-field gel electrophoresis.
AB  - Pulsed-field gel electrophoresis (PFGE) and multilocus enzyme electrophoresis
      (MLEE) were compared in this study of 65 Enterococcus faecalis isolates recovered
      over a 20-year period from diverse geographic sources. Clonal relationships
      recognized by PFGE were also recognized by MLEE; however, MLEE recognized as
      greater number of isolates as belonging to clonal groups than did PFGE. Both
      techniques were reproducible and discriminatory, but MLEE more readily recognized
      relationships among large numbers of isolates. MLEE confirmed the previously
      reported clonal spread of beta-lactamase-producing E. faecalis to six hospitals
      in five states. MLEE provided a useful population framework of the E. faecalis
      isolates in this sample, while PFGE was able to differentiate among isolates
      within some MLEE clonal groups.

PMID- 8576344
TI  - Immunomagnetic PCR and DNA probe for detection and identification of
      Porphyromonas gingivalis.
AB  - The aim of the study that we describe was to combine an immunomagnetic separation
      and a PCR followed by dot blot hybridization with a DNA probe for the detection
      and identification of Porphyromonas gingivalis. Immunomagnetic particles were
      coated with monoclonal antibody specific for P. gingivalis and were incubated
      with a suspension containing seven oral bacterial species spiked with various
      dilutions of P. gingivalis. Beads with their load of bound bacterial were boiled
      in water, and the target DNA in the supernatant was amplified with a primer pair
      to generate a 593-bp PCR fragment specific for P. gingivalis. Finally, the
      product of amplification was detected by dot blot hybridization with a
      digoxigenin-labeled 593-bp probe. The detection limit was determined to be 100
      bacterial cells per ml. The immunomagnetic-PCR/DNA probe procedure described here
      should be useful for the rapid, specific, and sensitive detection and
      identification of P. gingivalis in clinical samples.

PMID- 8576345
TI  - Molecular probes for diagnosis of fungal infections.
AB  - We have developed 21 specific nucleic acid probes which target the large subunit
      rRNA genes from Aspergillus flavus, Aspergillus fumigatus, Aspergillus glaucus,
      Aspergillus niger, Aspergillus terreus, Blastomyces dermatitidis, Candida
      albicans, Candida (Torulopsis) glabrata, Candida guilliermondii, Candida kefyr,
      Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis,
      Coccidioides immitis, Cryptococcus neoformans var. gattii, Cryptococcus
      neoformans var. neoformans, Filobasidiella neoformans var. bacillispora,
      Filobasidiella neoformans var. neoformans, Histoplasma capsulatum,
      Pseudallescheria boydii, and Sporothrix schenckii. A section of the 28S rRNA gene
      from approximately 100 fungi, representing about 50 species of pathogens and
      commonly encountered saprophytes, was sequenced to develop universal PCR primers
      and species-specific oligonucleotide probes. Each step in the process of
      detection and identification was standardized to a common set of conditions
      applicable without modification to all fungi of interest and all types of
      clinical specimens. These steps consist of DNA extraction by boiling specimens in
      an alkaline guanidine-phenol-Tris reagent, amplification of a variable region of
      the 28S rRNA gene with universal primers, and amplicon identification by probe
      hybridization or DNA sequencing performed under conditions identical for all
      fungi. The results obtained by testing a panel of fungal isolates and a variety
      of clinical specimens indicate a high level of specificity.

PMID- 8576347
TI  - Enzyme-linked immunosorbent assay-based inhibition test for neutralizing
      antibodies to polioviruses as an alternative to the neutralization test in tissue
      culture.
AB  - A poliovirus-binding inhibition test (PoBI test) was established for the
      quantitative determination of antibodies to polioviruses and was evaluated in
      comparison with the conventional neutralization test (NT). The first step of the
      PoBI test is an incubation of serial dilutions of test samples with inactivated
      poliovirus followed by the detection of free viral epitopes by a double antibody
      sandwich enzyme-linked immunosorbent assay with type-specific capture polyclonal
      antisera and type-specific neutralizing monoclonal indicator antibodies. A
      comparison of the PoBI test with the conventional NT for antibodies to all three
      types in 100 human serum samples showed excellent correlations (r > 0.95) over a
      wide range of antibody concentrations. The PoBI test, not necessitating live
      virus and tissue culture facilities, could be a simple alternative to the NT, and
      the principle of the assay is potentially applicable to other microbial systems.

PMID- 8576346
TI  - Physiological traits associated with success of Candida albicans strains as
      commensal colonizers and pathogens.
AB  - DNA fingerprinting with the moderately repetitive sequence Ca3 has repeatedly
      identified groups of genetically similar strains of Candida albicans that are
      more frequently isolated than other groups of strains from human hosts in a
      geographical locale. Members of these groups are found in approximately 30% of
      healthy individuals and in up to 70% of patients suffering from candidiasis. The
      high prevalence of these strains implies that they are more successful in
      colonizing human hosts and in causing disease than other strains (J. Schmid,
      Clin. Adv. Treatment Fungal Infect. 4(6):12-16, 1993). In the present study, we
      have compared one such group of highly prevalent strains with other strains from
      the same locale to identify physiological traits a larger number of chemicals
      than other strains in a resistogram assay. When resistance to individual
      chemicals used in the resistogram assay was analyzed, strains from the group of
      highly prevalent strains were significantly more often resistant to boric acid,
      cetrimide, chlorhexidine, 5-fluorocytosine, and high sodium chloride
      concentrations than other strains. Strains from the group of highly prevalent
      strains also adhered significantly (1.5 times) better to saliva-coated surfaces
      than did other strains. Because members of highly prevalent groups of strains are
      the most common infectious agents in candidiasis, these physiological traits may
      be involved in determining not only the success of C. albicans in colonizing
      human hosts in general but also its ability to cause disease. Sodium chloride
      resistance and increased adherence were also associated with infectious isolates
      outside the group of highly prevalent strains, indicating that they may be of
      particular importance in pathogenesis.

PMID- 8576348
TI  - Greater diversity of hepatitis C virus genotypes found in Hong Kong than in
      mainland China.
AB  - A hepatitis C virus (HCV) genotyping PCR assay based on type-specific primers was
      expanded to include genotype 6a as well as genotypes 1a, 1b, 2a, and 3a. The
      nucleotide sequences of a 194-bp fragment in the center of the HCV core gene
      showed that the homologies between genotype 6a and genotypes 1a, 1b, 2a, 2b, 3a,
      and 5 were 81.2, 82.1, 73.8, 77.3, 81.4, and 78.9%, respectively. A high degree
      of homology (99.6%) was seen in the amplified core region among eight clinically
      unrelated genotype 6a isolates. Although the Hong Kong Chinese patients had
      predominantly genotype 1b (70%), it was noteworthy that genotype 6a was the
      second most common genotype (14%). Four other HCV genotypes--1a, 1b, 2a, and 2b-
      were also present. In contrast, HCV infection by mainland China was confined to
      genotypes 1b and 2a. Thus, we found a greater diversity of HCV genotypes in Hong
      Kong than in mainland China.

PMID- 8576349
TI  - Development and testing of monoclonal antibody-based rapid immunodiagnostic test
      kits for direct detection of Vibrio cholerae O139 synonym Bengal.
AB  - We report on the development and testing of two monoclonal antibody-based rapid
      immunodiagnostic test kits, BengalScreen, a coagglutination test, and Bengal DFA,
      a direct fluorescent-antibody test, for direct detection of Vibrio cholerae O139
      synonym Bengal in clinical and environmental specimens. The BengalScreen test
      requires less than 5 min to complete and can be used in the field. Bengal DFA,
      being more sensitive than BengalScreen, requires only one reagent and less than
      20 min for detection and enumeration of V. cholerae O139 synonym Bengal. In tests
      for specificity, all 40 strains of V. cholerae O139 reacted with both test kits,
      whereas 157 strains of heterologous species examined did not, yielding 100%
      specificity in this study. A field trial was conducted in with both BengalScreen
      and Bengal DFA, and the results were compared with those obtained by conventional
      culture methods. BengalScreen demonstrated a sensitivity of 95%, a specificity of
      100%, a positive predictive value of 100%, and a negative predictive value of
      94%. Results obtained by Bengal DFA, on the other hand, were 100% sensitive and
      100% specific and yielded 100% positive and negative predictive values compared
      with culture methods. In a second evaluation, 93 stool specimens from Mexico that
      were negative for V. cholerae O139 by culture were also tested with both the
      BengalScreen and Bengal DFA kits. None of the 93 specimens were positive for V.
      cholerae O139 by both tests. A concentration method was optimized for screening
      of environmental water samples for V. cholerae O139 synonym Bengal with rapid
      test kits. BengalScreen results were unequivocally positive when water samples
      contained at least 2.0 x 10(3) CFU/ml, whereas Bengal DFA demonstrated an
      unequivocally positive reaction when the water sample contained at least 1.5 x
      10(2) CFU/ml. When Bengal DFA was compared with conventional culture methods for
      enumeration of V. cholerae O139 synonym Bengal organisms, no difference was
      observed.

PMID- 8576350
TI  - Genotypic and phenotypic characterization of Helicobacter cinaedi and
      Helicobacter fennelliae strains isolated from humans and animals.
AB  - By DNA-DNA hybridization, we classified 26 human strains, 4 dog and cat strains,
      and 4 hamster strains putatively identified as Helicobacter cinaedi as well as 2
      human strains and 2 animal strains of Helicobacter fennelliae. All but one human
      strain belonged to the same hybridization group as the type strain of H. cinaedi.
      The animal strains also appeared to belong to this hybridization group. Both
      human strains of H. fennelliae were shown to be H. fennelliae by DNA-DNA
      hybridization, but both animal strains were less than 15% related to the type
      strain. All strains were also characterized by plasmid profiles and ribotyping.
      Plasmids were found in 23% of the human strains, 100% of the hamster strains, and
      33% of the dog and cat strains. Human strains were essentially identical by
      ribotyping, but were clearly differentiated from the hamster and dog and cat
      strains. Some strains may be difficult to culture on primary isolation; we found
      that our strains grew well on anaerobic CDC agar, brucella agar, and tryptic soy
      agar II. Our H. cinaedi and H. fennelliae strains differed from those previously
      described because some were resistant to cephalothin: some H. cinaedi strains
      were also resistant to nalidixic acid. All isolates were also characterized by
      antimicrobial susceptibility testing. We found that human strains of H. cinaedi
      were more resistant to clindamycin and erythromycin than were animal isolates;
      19% of the human strains were resistant to ciprofloxacin. Therefore, we recommend
      that antimicrobial susceptibility results be obtained before initiating therapy
      for H. cinaedi and H. fennelliae infections.

PMID- 8576352
TI  - Differentiation by molecular typing of Mycobacterium bovis strains causing
      tuberculosis in cattle and goats.
AB  - Forty Mycobacterium bovis isolates from cattle and goats were analyzed by using
      different repetitive genetic markers. The 23 M. bovis strains from goats were
      found to carry six to eight copies of the insertion sequence IS6110. In contrast,
      most of the bovine isolates contained only a single copy of this element. The
      standardized IS6110 fingerprinting by restriction fragment length polymorphism
      (RFLP), described for Mycobacterium tuberculosis strains, allowed the
      differentiation of caprine strains. Although this method was not useful for
      typing bovine isolates, the repetitive elements pTBN12 and DR proved to be
      suitable for this purpose. A procedure using PCR which amplifies IS6110 in the
      outward direction was found to be as sensitive as RFLP for typing M. bovis
      strains from goats. The use of PCR and RFLP methods based on the IS6110
      polymorphism would be useful for epidemiological studies of caprine tuberculosis.
      The results are consistent with different strains of M. bovis being implicated in
      bovine and caprine tuberculosis.

PMID- 8576351
TI  - Disseminated Encephalitozoon (Septata) intestinalis infection in a patient with
      AIDS: novel diagnostic approaches and autopsy-confirmed parasitological cure
      following treatment with albendazole.
AB  - Encephalitozoon intestinalis is a recently described microsporidian which causes
      intestinal and disseminated infections in severely immunocompromised patients
      with AIDS. Preliminary data suggest that albendazole can be an effective therapy
      for patients with E. intestinalis infection. However, relapses have been reported
      following treatment in some cases. These results were based upon examination of
      cytologic, biopsy, or stool samples with an inherent sampling bias. This report
      documents the first postmortem evaluation of a patient with E. intestinalis
      infection treated with albendazole. Antemortem microsporidial diagnosis was
      performed on nasal mucosal smear and duodenal biopsy specimens by electron
      microscopy and a newly developed indirect fluorescent-antibody method based upon
      in vitro cultivation of the organism. This case represents the initial report of
      using nasal cytologic specimens for ultrastructural and antibody-based species
      level diagnosis of microsporidiosis. Following successful treatment of this
      infection with albendazole, the patient died of other causes. A thorough autopsy
      examination failed to reveal the presence of E. intestinalis in any tissue,
      providing confirmatory evidence for a complete parasitological cure with
      albendazole.

PMID- 8576353
TI  - Genotyping human papillomavirus type 16 isolates from persistently infected
      promiscuous individuals and cervical neoplasia patients.
AB  - Nucleotide sequence variation in the noncoding region of the genome of human
      papillomavirus type 16 (HPV16) was determined by direct sequencing and single
      strand conformation polymorphism analysis of DNA fragments amplified by PCR.
      Individuals of diverse sexual promiscuity and/or cervicopathology were studied.
      In a group of 14 healthy, monogamous HPV16-positive females, only two HPV16
      sequence variants could be documented. Among 17 females and 3 males with multiple
      sex partners and living in the same geographical region, nine sequence variants
      were found, whereas among 7 patients with cervical neoplasia from another region,
      five variants were detected. Although numbers are limited, in the group of
      individuals at high risk of acquiring a sexually transmitted disease or with
      cervical neoplasia, a larger number of HPV16 sequence variants was encountered
      (two types among 14 individuals versus nine types among 20; Fisher's exact test,
      P = 0.07). Seven of the individuals were sampled repeatedly over time. For these
      persistently infected women, no differences in HPV16 sequences were detected,
      irrespective of promiscuity, and persistence of a single viral variant, spread
      over multiple anatomic sites, for more than 2 years could be demonstrated. This
      indicates that viral persistence may be a common feature and that successful
      superinfection with a new variant may be rare, despite a potentially high
      frequency of viral reinoculation.

PMID- 8576354
TI  - Comparison of methods for obtaining serum opacity factor from group A
      streptococci.
AB  - Streptococcal serum opacity factor (OF) is an important type-specific strain
      marker produced by certain serotypes of group A streptococci (GAS). The accurate
      determination of OF production and subsequent serotyping of a strain require a
      reliable method for extracting OF. Traditional OF extraction methods have
      utilized either culture supernatants or Lancefield HCl extracts. However, these
      methods do not consistently yield adequate amounts of OF for accurate
      characterization of all strains. To improve the accuracy of OF utilized and found
      to be reproducibly sensitive and suitable for routine laboratory use. A total of
      3,014 GAS were examined for OF production by each of the three methods. The SDS
      extraction method accurately detected OF in all 1,302 OF-producing strains,
      whereas the HCl extraction method correctly identified 1,202 (92%) and the
      supernatant method identified only 1,141 (88%) of the isolates. When the 1,302 OF
      producing strains were further evaluated to determine if sufficient OF had been
      extracted for reliable OF serotyping, 1,147 (88%) of the SDS extracts were found
      to be satisfying compared with 1,081 (83%) of the HCl extracts and only 936 (72%)
      of the culture supernatants. The improved ability to characterize OF-producing
      strains by using SDS was statistically significant compared with the results
      obtained by the other two techniques. This technique offers distinct advantages,
      including enhanced detection of OF production and improved reliability of
      serotyping OF-producing GAS.

PMID- 8576355
TI  - Identification of widespread Helicobacter hepaticus infection in feces in
      commercial mouse colonies by culture and PCR assay.
AB  - The identification of a new murine pathogen, Helicobacter hepaticus, and its
      association with chronic active hepatitis and liver tumors prompted an evaluation
      of the prevalence of H. hepaticus in commercially available mice. Of the 28
      different strains or stocks, totaling 160 mice from four major commercial
      vendors, cultured for H. hepaticus, 100% of mice from two outbred strains from
      one vendor were infected with H. hepaticus, whereas 9 of 13 inbred mouse strains
      from another vendor were infected. This high prevalence of H. hepaticus
      established a need for a rapid and reproducible, noninvasive assay for the
      screening of colony-maintained mice being used for biomedical research. The
      culturing of fecal material by using 0.45-microns-pore- size filtration for H.
      hepaticus consistently yielded reproducible results but required extended periods
      of time. (1 to 3 weeks) to obtain a definitive answer. Although it is rapid, the
      use of a direct PCR-based detection assay with fecal specimens is restricted by
      inhibitory agents. to circumvent these inhibitory agents and to augment our H.
      hepaticus culture technique, we have developed a novel PCR system in which the
      bacteria are isolated from fecal material in the presence of
      polyvinylpyropyrollidone and lysed by treatment with Chelex 100. The PCR is
      performed with Tth polymerase supplemented with a polymerase enhancer. By this
      PCR method, 24 H. hepaticus culture-positive and 30 H. hepaticus culture-negative
      fecal samples were correctly identified. Moreover, two samples which were PCR
      positive and culture negative initially were positive by both methods upon
      retesting of fresh material. Southern blot hybridizations and sequencing of PCR
      products showed them to be H. hepaticus specific. A comparison of results
      obtained under identical conditions indicated a 100-fold increase in sensitivity
      with Tth polymerase over Taq polymerase. This PCR method can be used as a
      noninvasive means of rapidly screening large numbers of colony mice for H.
      hepaticus.

PMID- 8576356
TI  - Typing of Pneumocystis carinii strains with type-specific oligonucleotide probes
      derived from nucleotide sequences of internal transcribed spacers of rRNA genes.
AB  - We have recently developed a method for typing Pneumocystis carinii strains that
      infect humans. The method takes advantage of nucleotide sequence variations in
      internal transcribed spacers (ITSs) of the rRNA genes of P. carinii. To date, two
      types of nucleotide sequences (designated types A and B) have been found in the
      ITS1 region, and three types of nucleotide sequences (designated types a, b and
      c) have been found in the ITS2 region. Of the six potential combination types, we
      have detected four, designated types Ac, Bb, Ba, and Bc. To simplify typing, we
      have designed five oligonucleotide probes, probes 1-A, 1-B, 2-a, 2-b, and 2-c,
      which are specific to ITS1 type A and type B and ITS2 type a, type b, and type c,
      respectively, of P. carinii strains that infect humans. We also have designed an
      oligonucleotide which reacts specifically with P. carinii strains that infect
      rats. The ITS region were amplified by PCR, and the PCR products were then probed
      with these type-specific oligonucleotide probes. Typing with the type-specific
      oligonucleotide probes was found to be effective with specimens containing only
      one type of P. carinii. These methods are rapid and simple to perform and will be
      useful for studying the epidemiology of P. carinii infections.

PMID- 8576357
TI  - Evaluation of a novel serotyping system for hepatitis C virus: strong correlation
      with standard genotyping methodologies.
AB  - Direct sequencing and analysis of viral genomes are definitive methods for
      identifying various hepatitis C virus (HCV) genotypes. However, HCV genome
      sequencing methods are cumbersome and unsuitable for analyzing large numbers of
      clinical samples. We have developed a convenient, reliable, and reproducible RIBA
      strip immunoblot assay system for determining HCV serotype. Briefly, the assay
      consists of an immunoblot strip on which there are five lanes of immobilized
      serotype-specific HCV peptides from the nonstructural (NS-4) and core regions of
      the genomes of HCV types 1,2, and 3. HCV serotype is deduced by determining the
      greatest intensity of reactivity to the NS-4 serotype-specific HCV peptide band
      in relation to the intensity of the human immunoglobulin G internal control bands
      on each strip. HCV core peptide reactivity is used only in the absence of NS-4
      reactivity. We used this assay to successfully serotype a high percentage of sera
      from well-documented HCV-infected patients. Our serotyping results correlated 99%
      with the findings from the standard restriction fragment length polymorphism
      genotyping methods. Less than 5% of the serum samples were untypeable. For a
      selected group of alpha interferon-treated patients we observed that the
      nonresponders (76.2%) and a majority of the responders who relapsed (72.2%) had
      type 2 HCV infection. A small population (n= 8) of complete responders was split
      3:4:1 as type 1, type 2, and type 3, respectively. Our data indicate that this
      new serotyping assay has the potential to be a highly specific and reliable
      method for typing of HCV infection in patients.

PMID- 8576358
TI  - Optimization of detection of cytomegalovirus viremia in transplantation
      recipients by shell vial assay.
AB  - Cytomegalovirus (CMV) viremia is a widely used laboratory marker of CMV disease
      following transplantation and is additionally used to trigger preemptive
      antiviral therapy. Despite this, the optimal method for diagnosing CMV viremia in
      transplantation recipients remains unknown. To determine the sampling frequency
      and blood volume required for the optimal diagnosis of viremia by shell vial
      assay, a prospective study of 46 viremic transplantation recipients was
      conducted. Blood specimens (2.5 and 5 ml) were collected twice, 3 h apart, at a
      median of 1.4 days (range, 1 to 3 days) after the triggering shell vial-positive
      blood had been collected. Considering a single 2.5-ml specimen, an average of
      only 40% of previously viremic patients had documented CMV in their blood: this
      increased to 50% when a second 2.5-ml sample of blood was collected 3 h later.
      The yields of two 2.5-ml versus two 5-ml samples were 50 versus 61%,
      respectively. Viremia as detected by shell vial assay is intermittent, and
      increasing the frequency and volume of blood sampling increases its diagnosis.
      These results have implications in diagnosis of CMV infection and its preemptive
      therapy.

PMID- 8576359
TI  - Pathogenic, immunologic, and molecular differences between two Ehrlichia risticii
      strains.
AB  - Ehrlichia risticii is the causative agent of Potomac horse fever (PHF), an acute
      infectious disease of horses. In the last few years, there have been several
      reports of PHF cases occurring even in vaccinated horses. We isolated a new
      strain of E. risticii (90-12 strain) from a vaccinated horse suffering from
      clinical PHF. The major pathogenic, immunologic, and molecular differences
      between the 90-12 strain and the 25-D stain, which was originally isolated during
      the outbreaks in 1984, were studied. The 90-12 strain was more pathogenic for
      mice and horses compared with the 25-D strain. In enzyme-linked immunosorbent
      assay and immunofluorescence assay with mouse and horse antisera of both the
      strains, two- to fourfold differences were observed between (immunoblot) with
      mouse and horse antisera and also with the recombinant clone-specific antibodies.
      Though several antigens were similar in both the strains, there were significant
      differences between them in the 110-, 85-, 70-, 51-, and 33-kDa antigens. The 85
      kDa antigen was present only in the 90-12 strain but cross-reacted with a 50-kDa
      antigen of the 25-D strain. The 51-kDa antigens of both strains had different
      migration patterns, Southern blot hybridization of the genome from both the
      strains with DNA probes made from the 51-, 55-, and clones for both the strains,
      whereas the probe of the 85-kDa clone showed a completely different pattern. The
      16S rRNA gene sequences from the two strains were identical. Neither strain
      replicated in gamma interferon-treated mouse peritoneal macrophages. In in vitro
      neutralization assay, sera from the 25-D strain-infected horse neutralized the
      homologous strain but did not neutralize the 90-12 strain, whereas sera from the
      90-12 strain-infected horse neutralized both the strains. In mouse protection
      experiments, there was complete homologous protection. But in cross-protection,
      mice immunized with the 25-D strain were only partially protected against
      challenge with the 90-12 strain, whereas mice immunized with the 90-12 strain
      were completely protected against the 25-D strain challenge. These results
      clearly indicate that there are major differences between the 90-12 and 25-D
      strains which may have implications regarding the vaccine failure for PHF and the
      development of an efficient vaccine.

PMID- 8576360
TI  - Detection and identification of mycobacteria by DNA amplification and
      oligonucleotide-specific capture plate hybridization.
AB  - We have developed an easy and rapid detection and identification system for the
      diagnosis of mycobacterial diseases. The system is based on selective
      amplification by PCR of mycobacteria with primers based on the genes coding for
      16S rRNA. During PCR, a label (digoxigenin-11-dUTP) is incorporated with
      biotinylated species-specific oligonucleotides (oligonucleotide-specific capture
      plate hybridization [OSCPH]. One oligonucleotide specific for the genus
      Mycobacterium and seven species-specific (Mycobacterium tuberculosis, M. avium,
      M. intracellulare, M. scrofulaceum, M. xenopi, M. genavense, and M. chelonae)
      oligonucleotides were designed as capturing probes. After specific hybridization,
      an enzyme immunoassay reveals the specifically bound complexes and thus permits
      identification of the mycobacterium. A total of 70 mycobacterial strains were
      tested. For 69 strains, results concordant with conventional identification were
      obtained. One M. chelonae strain was negative with the M. chelonae probe and was
      later reidentified as M. fortuitum. Moreover, for 15 clinical samples suspected
      of harboring nontuberculous mycobacteria, OSCPH was able to confirm all culture
      results and could identify one M. genavense infection for which standard culture
      results were negative. PCR-OSCPH is easily applicable and much faster than
      culture. It could become a valuable alternative approach for the diagnosis of
      mycobacterial infections.

PMID- 8576361
TI  - Geographical clustering of human T-cell lymphotropic virus type 1 infection in
      Honduras.
AB  - Geographical clustering of human T-cell lymphotropic virus type 1 (HTLV-1)
      infection has been identified in the nonmestizo communities in several cities
      along the Atlantic coast of Honduras. Of the 2,651 serum samples tested, 122
      samples were repeatedly reactive for HTLV-1 antibodies in two different enzyme
      immunoassays and 3 were indeterminate. These sera did not react in the HTLV-2
      specific antibody tests. The presence of HTLV-1 antibodies was confirmed by HTLV
      1 immunoblots or Western blots (immunoblots), and the infection was verified by
      the detection of HTLV-1-specific genetic sequences in the cellular DNA by PCR.
      Genomic DNA from the peripheral blood mononuclear cells was first tested with
      generic primers and probes that identified both HTLV-1 and HTLV-2. Next, all DNA
      samples that showed HTLV reactivity were tested by PCR with specific primers and
      probes that distinguished HTLV-1 sequences from those of HTLV-2. Our results
      indicate that only HTLV-1 infection was present in the blood of both mestizo and
      nonmestizo residents of 15 cities in the Republic of Honduras. The overall
      prevalence of HTLV-1 infection in the nonmestizo population was 8.1% (95%
      confidence limit, 6.6 to 9.7%). The mestizo population residing in the same
      geographical vicinities showed a HTLV-1 antibodies in 0.5% of serum samples
      tested (95% confidence limit, 0.6 to 1.7%), indicating a significantly greater
      prevalence of HTLV-1 infection in the nonmestizo population than in the mestizo
      ethnic groups living in Honduras (P = 0.0001). Since no HTLV-2 antibody
      reactivity or HTLV-2-specific genetic sequences were detected by PCR with
      different primers and probes, it was concluded that HTLV-2 infection was not
      present in the Honduran population groups we tested. Our study also suggested an
      endemic nature for this virus because there was no difference in the prevalence
      rate of HTLV-1 antibodies in the nonmestizo community living in the coastal towns
      of Honduras between 1989 and 1993. This is the first report of HTLV-1 cluster
      identification in Honduras, Central America.

PMID- 8576362
TI  - Comparison of PCR and standard cytological staining for detection of Pneumocystis
      carinii from respiratory specimens from patients with or at high risk for
      infection by human immunodeficiency virus.
AB  - The detection of Pneumocystis carinii DNA by PCR was compared with routine
      cytologic staining techniques (CYT). A total of 284 clinical respiratory
      specimens, including 137 bronchoalveolar lavage (BAL), 63 bronchoalveolar
      washing, 63 sputum, and 21 induced sputum samples, obtained from patients with or
      at high risk for human immunodeficiency virus infection were evaluated. Eighty
      specimens were positive by PCR, and 69 were positive by CYT. PCR was able to
      detect P. carinii in more bronchoalveolar washing specimens (15 versus 11) and in
      comparable BAL specimens (53 versus 54) compared with CYT. PCR was particularly
      more sensitive than CYT in detecting P. carinii in expectorated sputum (12 versus
      4 samples). Of the 19 patients whose respiratory specimens were positive for P.
      carinii by PCR but negative by CYT, 5 had P. carinii pneumonia (PCP) confirmed by
      subsequent BAL and transbronchial or mediastinal lymph node biopsy and 9 had a
      clinical course highly suggestive of acute PCP. Eleven (58%) of the 19 patients
      with discordant PCR and CYT results had received prior anti-PCP prophylaxis. In
      this clinical setting in particular and in the evaluation of sputum specimens,
      the ability of PCR to detect a low parasitic load suggests that this technique
      may become an important additional tool, along with current cytological methods,
      for the detection of P. carinii.

PMID- 8576363
TI  - Multilaboratory evaluation of screening methods for detection of high-level
      aminoglycoside resistance in enterococci. National Committee for Clinical
      Laboratory Standards Study Group on Enterococci.
AB  - Since the early 1970s, the synergistic activity of an aminoglycoside with a cell
      wall-active agent has been predicted by determining the ability of an
      enterococcus to grow in the presence of high levels of the aminoglycoside
      (usually > or = 2,000 micrograms/ml). However, a variety of media and
      concentrations of aminoglycosides has been used for this screening procedure. In
      the present study, we sought to optimize the agar dilution, broth microdilution,
      and disk diffusion tests used to detect high-level gentamicin and streptomycin
      resistance in enterococci. For dilution tests, brain heart infusion agar or broth
      gave the best growth and performance. For agar dilution, 500 micrograms of
      gentamicin per ml, 2,000 micrograms of streptomycin per ml, and an inoculum of 1
      x 10(6) CFU/ml were optimal, while for broth microdilution, 500 micrograms of
      gentamicin per ml, 1,000 micrograms of streptomycin per ml, and an inoculum of 5
      x 10(5) CFU/ml were best. Growth of more than one colony in the agar dilution
      test was determined to be the best indicator of high-level resistance. For disk
      diffusion, Mueller-Hinton agar, 120-micrograms gentamicin disks, and 300
      micrograms streptomycin disks with breakpoints of no zone for resistance and > or
      = 10 mm for susceptibility gave the best sensitivity and specificity if results
      for strains with zones of 7 to 9 mm are considered inconclusive, indicating that
      a broth or agar test should be performed to determine susceptibility or
      resistance.

PMID- 8576364
TI  - Molecular characterization and multilaboratory evaluation of Enterococcus
      faecalis ATCC 51299 for quality control of screening tests for vancomycin and
      high-level aminoglycoside resistance in enterococci.
AB  - Studies were conducted to validate the use of Enterococcus faecalis ATCC 51299
      (which is vancomycin resistant and resistant to high levels of gentamicin and
      streptomycin) and E. faecalis ATCC 29212 (which is susceptible to vancomycin and
      against which gentamicin or streptomycin and cell wall-active agents have
      synergistic kill activity) as controls in an agar screening test for vancomycin
      resistance and high-level streptomycin and gentamicin resistance and a broth
      microdilution screening test for high-level streptomycin and gentamicin
      resistance. Both organisms performed as expected in these tests and will serve as
      appropriate controls. However, E. faecalis ATCC 29212 was occasionally noted to
      produce light growth on the vancomycin screening plate with certain lots of agar.
      Quality control ranges for disk diffusion tests with disks with large amounts of
      streptomycin (300 micrograms) and gentamicin (120 micrograms) were established
      for E. faecalis ATCC 29212; zone limits are 16 to 22 mm for gentamicin and 14 to
      19 mm for streptomycin. No zones for inhibition were seen when E. faecalis ATCC
      51299 was tested with these high-content disks.

PMID- 8576365
TI  - Genomic study of Rickettsia akari by pulsed-field gel electrophoresis.
AB  - Pulsed-field gel electrophoresis of SmaI-, EagI-, and BssHII-digested DNA was
      used to perform restriction fragment length polymorphism analysis of Rickettsia
      akari strains isolated from humans, rodents, and mites in the United States and
      Ukraine. Although some differences in biological and serological characteristics
      were present between strains, the genomic studies demonstrated a high degree of
      intraspecies homogeneity of R. akari isolates. Our results confirm the value of
      pulsed-field gel electrophoresis-restriction fragment length polymorphism
      analysis for the identification of species of rickettsiae.

PMID- 8576366
TI  - Use of CHROMagar Candida medium for isolation of yeasts from dental samples.
AB  - A new differential medium, CHROMagar Candida, for the isolation of clinically
      important yeasts was investigated to determine its usefulness in facilitating the
      study of oral yeasts. The recovery of yeasts on the medium was not significantly
      different from the recovery on Sabouraud dextrose agar. The identities of 450
      green colonies on CHROMagar Candida, presumptively identified as Candida albicans
      on the basis of the manufacturer's instructions, were confirmed by testing for
      beta-N-acetylgalactosaminidase. Candida tropicalis also formed distinctive
      colonies, and other yeasts including Candida (Torulopsis) glabrata, Candida
      Parapsilosis, Candida Magnoliae, Candida lusitaniae, Candida Famata, Candida
      kefir, and Saccharomyces cerevisiae were readily distinguished from C. albicans
      and C. tropicalis isolates. CHROMagar Candida is a very useful medium, and its
      use will facilitate the study of yeasts associated with dental diseases.

PMID- 8576367
TI  - Comparison of SHARP signal system and Southern blot hybridization analysis for
      detection of cytomegalovirus in clinical specimens by PCR.
AB  - Thirty cytomegalovirus cell culture-positive samples were tested by the SHARP
      Signal System. Twenty-seven specimens (100% agreement) were identified by both
      methods. The SHARP Signal System is rapid (4 h), easy to perform, and potentially
      adaptable to automation.

PMID- 8576368
TI  - Assessment of Difco ESP 384 blood culture system by terminal subcultures: failure
      to detect Cryptococcus neoformans in clinical specimens.
AB  - Terminal subcultures were performed on 1,162 5-day negative blood culture sets
      which had been monitored by the Difco ESP 384, a continuous-monitor blood culture
      system. Of these, 16 (1.4%) had growth upon terminal subculture. The isolates not
      detected by the Difco ESP 384 were Cryptococcus neoformans (eight isolates),
      Candida albicans (one isolate), Staphylococcus aureus (two isolates) coagulase
      negative staphylococcus (three isolates), Bacillus sp. (one isolate), and
      Corynebacterium sp. (one isolate). Acridine orange staining was performed on 200
      randomly selected negative blood culture sets from the study group. Of these, two
      sets were positive and grew out C. neoformans, as did the terminal subculture. A
      review of patient's medical records indicated that many of these false-negative
      isolates were clinically insignificant. The Difco ESP 384 failed to detect 1.4%
      of the isolates in this study, 50% of which were C. neoformans, indicating a
      deficiency in the detection mechanism of the system. Further studies demonstrated
      that while these isolates (C. neoformans) grew in the Difco media, the system did
      not detect this growth when the standard 5-day protocol was used.

PMID- 8576369
TI  - PCR as a confirmatory test for human immunodeficiency virus type 1 infection in
      individuals with indeterminate western blot (immunoblot) profiles.
AB  - A combination of two PCR systems which amplify human immunodeficiency virus type
      1 (HIV-1) gag and pol DNA was used to elucidate the HIV-1 infection status of a
      group of individuals screening positive for anti-HIV but having indeterminate
      Western blot (immunoblot) profiles. The results obtained suggest PCR could be
      used to resolve such cases.

PMID- 8576370
TI  - Restriction fragment length polymorphism typing of clinical isolates of
      Mycobacterium tuberculosis from patients with pulmonary tuberculosis in Madras,
      India, by use of direct-repeat probe.
AB  - Large numbers of Mycobacterium tuberculosis isolates that were obtained from
      patients' sputa on diagnosis and during follow-up after short-course chemotherapy
      in Madras, India, have either no copy or only a single copy of IS6110. This poses
      a limitation for DNA fingerprinting with an IS6110-based probe to determine the
      frequency of exogenous reinfection versus that of endogenous reactivation. In the
      present study, we overcame this limitation by using an alternate probe, the
      direct-repeat element. Comparison of pre- and posttreatment isolates by direct
      repeat restriction fragment length polymorphism analysis indicated a high degree
      of endogenous reactivation among patients who have relapses after the successful
      completion of chemotherapy.

PMID- 8576371
TI  - Anti-purified protein derivative cell-enzyme-linked immunosorbent assay, a
      sensitive method for early diagnosis of tuberculous meningitis.
AB  - A cell-enzyme-linked immunosorbent assay method was developed for the diagnosis
      of tuberculous meningitis by determining anti-purified protein derivative
      antibody production by cells derived from cerebrospinal fluid and peripheral
      blood. Of 20 patients with clinical histories and CSF findings suggestive of
      tuberculous meningitis, 18 showed high production of anti-purified protein
      derivative immunoglobulin antibody from CSF-derived lymphocytes, while none of
      the controls showed such response.

PMID- 8576372
TI  - Haemophilus parainfluenzae biliary tract infection: rationale for an ascending
      route of infection from the gastrointestinal tract.
AB  - Haemophilus parainfluenzae was isolated from a bile specimen of a 56-year-old
      patient with elevated liver enzymes and chronic cholecystitis. Several factors
      contributing to nonbacteremic H. parainfluenzae infection of the biliary tract
      include (i) the not infrequent occurrence of H. parainfluenzae in stool
      specimens, (ii) the presence of an outer membrane protein similar to those found
      in enteric bacteria which facilitates adherence to the colonic mucosa, and (iii)
      an adequate supply of V factor (nicotinamide adenine dinucleotide) supplied from
      bile and the local flora, which is necessary for H. parainfluenzae's growth.
      Because H. parainfluenzae rarely occurs in the biliary tract, direct cultivation
      of bile specimens on chocolate agar seems unwarranted. However, bile specimens
      showing a gram-negative coccobacillus on a Gram-stained smear that fails to grow
      on routine media should be subcultured on chocolate agar.

PMID- 8576373
TI  - Comparison of MicroScan WalkAway system and Vitek system for identification of
      gram-negative bacteria.
AB  - In a prospective side-by-side comparison conducted from September through
      November 1994, we compared the MicroScan WalkAway system, a conventional
      biochemical identification system (Dade MicroScan, Inc., Sacramento, Calif.),
      with the Vitek system (bioMerieux Vitek, Hazelwood, Mo. [analysis software
      version AMS-RO8.2] for the identification of gram-negative bacteria. Three
      hundred thirty-one nonurine isolates and 493 urine isolates were tested. For
      nonurinary isolates, there was 91.5% agreement between the two methods. For
      urinary isolates, there was 97.4% agreement between the two methods. Overall,
      there was 95% agreement between the two systems. The results suggest that the
      current version of the MicroScan WalkAway system with conventional panels is
      essentially comparable to the current Vitek system.

PMID- 8576374
TI  - Case of recurrent Flavimonas oryzihabitans bacteremia associated with an
      implanted central venous catheter (Port-A-Cath): assessment of clonality by
      arbitrarily primed PCR.
AB  - Flavimonas oryzihabitans bacteremias, which occurred immediately after the
      flushing or use of an implanted central venous catheter (Port-A-Cath) in two
      patients at the same pediatric ward, were studied by arbitrarily primed PCR. We
      conclude that the colonization of the Port-A-Cath with F. oryzihabitans described
      here lasted for several months.

PMID- 8576375
TI  - Multiplex PCR for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in
      Genitourinary specimens.
AB  - We developed a multiplex PCR (M-PCR) assay for the simultaneous detection of
      Chlamydia trachomatis and Neisseria gonorrhoeae. M-PCR employed C. trachomatis
      specific primers KL1-KL2 and N. gonorrhoeae-specific primers HO1-HO3 and produced
      products of 241 and 390 bp, respectively. PCR products were easily detected by
      agarose gel electrophoresis and confirmed by Southern hybridization using
      labelled oligonucleotide probes. M-PCR had a sensitivity of 10 fg of C.
      trachomatis and N. gonorrhoeae DNA (equivalent to 1 to 2 genome copies). M-PCR
      detected the presence of C. trachomatis and N. gonorrhoeae DNA in 15 male
      urethral and 12 female endocervical specimens, 3 of which were positive for C.
      trachomatis, 18 of which were positive for N. gonorrhoeae and 6 of which were
      positive for both organisms. M-PCR was evaluated further by testing 200 male
      first void urine (FVU) specimens, of which 18 were positive by C. trachomatis PCR
      and Chlamydiazyme and 4 were positive by C. trachomatis PCR but negative by
      Chlamydiazyme. All 22 FVU specimens were positive by a confirmatory PCR using a
      second plasmid target and were positive by M-PCR. Ten of 11 men with cultures
      that were positive for N. gonorrhoeae had FVU specimens that were positive by
      both N. gonorrhoeae PCR and M-PCR. Two other men with negative N. gonorrhoeae
      urethral cultures had FVU specimens that were positive by N. gonorrhoeae PCR, by
      two confirmatory N. gonorrhoeae PCR assays using 165 rRNA and cytosine
      methyltransferase primers, and by M-PCR. The sensitivity of M-PCR for detecting
      C. trachomatis was 100% (22 of 22 specimens), compared with 81.8% (18 of 22
      specimens) for enzyme immunoassay. Sensitivity of M-PCR for N. gonorrhoeae was
      92.3% (12 of 13 specimens) compared with 84.6% (11 of 13 specimens) for urethral
      culture. The specificity of M-PCR was 100% for both C. trachomatis (178 of 13
      specimens) and N. gonorrhoeae (187 of 187 specimens). M-PCR testing of FVU
      specimens provided a sensitive and noninvasive method for detecting C.
      trachomatis and N. gonorrhoeae infection in men.

PMID- 8576376
TI  - Coexistence of antibodies to tick-borne pathogens of babesiosis, ehrlichiosis,
      and Lyme borreliosis in human sera.
AB  - Serum specimens from persons with or without Lyme borreliosis were analyzed by
      indirect fluorescent antibody staining methods for total immunoglobulins to
      Babesia microti, Ehrlichia chaffeensis (Arkansas strain), and Ehrlichia equi (MRK
      strain). There was serologic evidence of human exposure to multiple tick-borne
      agents in 15 (6.6%) of 227 serum samples obtained in Connecticut and Minnesota.
      Of these, 10 serum samples were from Connecticut patients who had erythema
      migrans and antibodies to Borrelia burgdorferi (range, 1:160 to 1:40, 960). A
      maximal antibody titer of 1:640 was noted for a B. microti infection, whereas
      titration end points of 1:640 and 1:1,280 were recorded for E. chaffeensis and E.
      equi seropositives, respectively. In specificity tests, there was no cross
      reactivity among the antisera and antigens tested for the four tick-borne
      pathogens. On the basis of serologic testing, a small group of persons who had
      Lyme borreliosis had been exposed to one or more other tick-borne agents, but
      there was no clinical diagnosis of babesiosis or ehrlichiosis. Therefore, if the
      clinical picture is unclear or multiple tick-associated illnesses are suspected,
      more extensive laboratory testing is suggested.

PMID- 8576377
TI  - Prevalence of Cyclospora species and other enteric pathogens among children less
      than 5 years of age in Nepal.
AB  - Stools from 124 Nepalese children aged 6 to 60 months with diarrhea were examined
      for organisms of the coccidian genus Cyclospora and for other enteric pathogens.
      Enterotoxigenic Escherichia coli, Giardia Lamblia, Campylobacter species,
      Cyclospora species, and Cryptosporidium species were the most common pathogens
      identified. Cyclospora species were detected in none of 74 children < 18 months
      of age compared with 6 (12%) of 50 children > or = 18 months of age (P = 0.004).

PMID- 8576378
TI  - Application of PCR for detection of toxigenic Corynebacterium diphtheriae strains
      isolated during the Russian diphtheria epidemic, 1990 through 1994.
AB  - A total of 250 Corynebacterium diphtheriae isolates from clinical cases and
      carriers in Russia were assayed by PCR directed at the A subunit of the
      diphtheria toxin gene to distinguish toxigenic from nontoxigenic strains; 170
      strains were positive as indicated by the presence of the 248-bp amplicon. The
      results of this PCR assay were in complete concordance with those of the standard
      immunoprecipitation assay (Elek), and the PCR assay is a useful tool for rapid
      identification in clinical laboratories.

PMID- 8576380
TI  - Comparison of Gram stain with DNA probe for detection of Neisseria gonorrhoeae in
      urethras of symptomatic males.
AB  - The comparison of Gram-stained urethral smears with Gen-Probe for the detection
      of Neisseria Gonorrhoeae in the urethras of males with symptomatic urethritis
      revealed a 99.6% correlation between the two methods. A simple Gram stain would
      appear to be the method of choice for the detection of gonorrhea in symptomatic
      males, because it is much less expensive and much more rapid than the Gen-Probe
      method.

PMID- 8576379
TI  - Intestinal cytomegalovirus disease in immunocompromised patients may be ruled out
      by search for cytomegalovirus DNA in stool samples.
AB  - Cytomegalovirus (CMV) PCR from stool specimens was adopted as a diagnostic tool
      for patients with suspected CMV colitis. After being established, the method was
      evaluated in 17 AIDS patients and 19 other immunocompromised patients by
      comparison of PCR results with clinical, histological, and microbiological or
      virological data. CMV PCR was positive in 4 symptomatic patients with proven CMV
      colitis and negative in 15 of 16 patients without characteristic histopathology.
      Neither CMV immunoglobulin G seropositivity nor intestinal symptoms alone were
      significantly associated with positive PCR results, but severe active systemic
      CMV infection may lead to a positive PCR. Absence of CMV DNA in stool samples may
      prove useful in ruling out CMV related colitis.

PMID- 8576381
TI  - Bacillus licheniformis prosthetic aortic valve endocarditis.
AB  - A 73-year old man developed an acute prosthetic aortic valve dehiscence for which
      emergent operation was undertaken. The intraoperative evidence of an aortic
      annular disruption and of a subannular abscess led to the hypothesis that an
      endocarditis process was involved. The aortic valve was replaced with a stentless
      porcine bioprosthesis. Cultures taken intraoperatively from the aortic area had a
      pure growth of aerobic, spore-forming, gram-positive bacilli identified as
      Bacillus licheniformis. The patient responded to specific antibiotic therapy with
      no relapse at a 20-month follow-up. The potentiality of B. licheniformis as a
      pathogen should be reconsidered.

PMID- 8576382
TI  - Use of molecular analysis in pathophysiological investigation of late-onset
      neonatal Escherichia coli meningitis.
AB  - We describe one case of late-onset neonatal Escherichia coli meningitis
      associated with urinary tract infection. Two genotypic methods revealed that the
      E. coli isolates obtained from blood, feces, and cerebrospinal fluid shared the
      same pattern, which was different from the unique pattern obtained for the
      isolates recovered from the urine and the tracheal aspirate. Our study supports
      passage of bacteria through the gastrointestinal mucosa to the bloodstream as the
      initial event, with subsequent meningeal localization.

PMID- 8576383
TI  - Evaluation of sampling sites for detection of upper respiratory tract carriage of
      Streptococcus pneumoniae and Haemophilus influenzae among healthy Filipino
      infants.
AB  - Two sampling techniques, nasal swabbing and oropharyngeal swabbing, for detection
      of the upper respiratory tract carriage of Streptococcus pneumoniae and
      Haemophilus influenzae were studied prospectively with 296 healthy Filipino
      infants at various ages: 6 to 8, 10 to 12, 14 to 17, 18 to 22, 32 to 39, and 46
      to 65 weeks. In all age groups S. pneumoniae was isolated significantly more
      often (P < 0.0001) from the nasal site than from the oropharyngeal site. H.
      influenzae was found equally often at both sites.

PMID- 8576384
TI  - Relevance of culturing Candida species from intravascular catheters.

PMID- 8576385
TI  - Investigation of hospital-acquired infections due to Alcaligenes denitrificans
      subsp. xylosoxidans by DNA restriction fragment length polymorphism.

PMID- 8576386
TI  - Development of nested PCR based on the ViaB sequence to detect Salmonella typhi.

PMID- 8576387
TI  - Functional localization by neurophysiologic and neuroimaging techniques.

PMID- 8576388
TI  - Mapping function in the human brain with magnetoencephalography, anatomical
      magnetic resonance imaging, and functional magnetic resonance imaging.
AB  - Integrated analyses of human anatomical and functional measurements offer a
      powerful paradigm for human brain mapping. Magnetoencephalography (MEG) and EEG
      provide excellent temporal resolution of neural population dynamics as well as
      capabilities for source localization. Anatomical magnetic resonance imaging (MRI)
      provides excellent spatial resolution of head and brain anatomy, whereas
      functional MRI (fMRI) techniques provide an alternative measure of neural
      activation based on associated hemodynamic changes. These methodologies constrain
      and complement each other and can thereby improve our interpretation of
      functional neural organization. We have developed a number of computational tools
      and techniques for the visualization, comparison, and integrated analysis of
      multiple neuroimaging techniques. Construction of geometric anatomical models
      from volumetric MRI data allows improved models of the head volume conductor and
      can provide powerful constraints for neural electromagnetic source modeling.
      These approaches, coupled to enhanced algorithmic strategies for the inverse
      problem, can significantly enhance the accuracy of source-localization
      procedures. We have begun to apply these techniques for studies of the functional
      organization of the human visual system. Such studies have demonstrated multiple,
      functionally distinct visual areas that can be resolved on the basis of their
      locations, temporal dynamics, and differential sensitivity to stimulus
      parameters. Our studies have also produced evidence of internal retinotopic
      organization in both striate and extrastriate visual areas but have disclosed
      organizational departures from classical models. Comparative studies of MEG and
      fMRI suggest a reasonable but imperfect correlation between electrophysiological
      and hemodynamic responses. We have demonstrated a method for the integrated
      analysis of fMRI and MEG, and we outline strategies for improvement of these
      methods. By combining multiple measurement techniques, we can exploit the
      complementary strengths and transcend the limitations of the individual neuro
      imaging methods.

PMID- 8576389
TI  - Dynamic neuroimaging of brain function.
AB  - To fully characterize the brain processes underlying sensorimotor and cognitive
      function, the spatial distribution of active regions, their interconnected
      regions must be measured. We describe methods for imaging brain sources from
      surface-recorded EEG and magnetoencephalographic data, called electromagnetic
      source imaging (EMSI). EMSI provides brain source locations within the common
      framework of magnetic resonance (MR) images of brain anatomy. This allows
      integration of data from other functional brain imaging methods, like positron
      emission tomography and functional MR imaging, which can improve the accuracy of
      EMSI localization. EMSI also provides submillisecond temporal resolution of the
      dynamic processes within brain systems. Examples are given of applications to
      visual perceptual and attentional studies.

PMID- 8576391
TI  - A new high-frequency magnetic stimulator with an oil-cooled coil.
AB  - A new high frequency magnetic stimulator, Labmag, is described which may be used
      in clinical neurophysiology and for the treatment of spasticity in multiple
      sclerosis. In order to avoid heating of the coil during repetitive stimulation,
      an oil/air cooling system was employed. The magnetic stimulus waveform is a half
      cosine with a rise time of 200 microseconds and a pulse width of 400 microseconds
      induced by alternating capacitor voltage. The Labmag product was compared with a
      commercially available high frequency stimulator, MagPro. The electric fields
      induced by Labmag were half the size of those induced by MagPro at identical
      stimulus intensities. Using a leaky integrator to simulate the effects on
      neurons, only minor differences in integrated electric fields were observed.
      There were no changes of the electric fields in relation to coil geometry. A
      minor difference in electric fields (1.0 +/- 0.8%) was observed when the polarity
      of the capacitor voltage alternated. Compound muscle action potentials (CMAPs)
      evoked by transcranial magnetic stimulation were recorded from the first dorsal
      interosseous muscle (FDI) in eight subjects. Threshold intensities of CMAPs
      evoked by Labmag (58 +/- 7%) were significantly smaller (p < 0.05) than threshold
      intensities obtained with MagPro (63 +/- 8%). Peak-to-peak amplitudes, P-Pamps,
      of CMAPs were significantly smaller after single stimulations with Labmag at
      stimulation intensities of 130 and 140% of threshold intensity.

PMID- 8576390
TI  - Comparative assessment of sensorimotor function using functional magnetic
      resonance imaging and electrophysiological methods.
AB  - Accurate assessment of the location of the sensorimotor cortex is important in
      presurgical investigation of and planning for patients with lesions impinging on
      this region. In this review, the relationship between the assessment of
      sensorimotor cortex by invasive electrophysiological mapping and functional
      magnetic resonance imaging (fMRI) is discussed. A number of areas are covered:
      (a) brief backgrounds of MRI and fMRI are provided, (b) existing fMRI literature
      of sensorimotor cortex activation is surveyed, (c) results of fMRI sensorimotor
      studies and intracranial somatosensory evoked potential (SEP) recordings and
      cortical stimulation in neurosurgical patients are compared, and (d) the locus of
      fMRI activation is discussed in the light of cortical generators of SEP
      components.

PMID- 8576392
TI  - Endogenous event-related potentials in term and preterm infants.
AB  - Event-related brain potentials generated in an auditory oddball paradigm were
      recorded in term and preterm infants. The amplitudes of these brain potentials
      were significantly larger when generated by a rare improbable stimulus compared
      to a common frequently presented stimulus. While the magnitude of this novelty
      detection effect depended on the gestational status (full term and preterm) of
      the infant, these findings suggest the developmental continuity of cognitive
      processes such as selective attention and recognition memory ordinarily observed
      in adults. The significant relationship between the amplitudes of these brain
      potentials and states conducive for sustained attention in infants further
      supports the endogenous nature of these potentials.

PMID- 8576394
TI  - Scalp distribution of electrical fields related to blink reflex.
AB  - In 20 subjects the supraorbital nerve was stimulated and R1 recorded from
      electrodes placed over the ipsilateral orbicularis oculi muscle and from
      locations Fz, F8, F7, Cz, C6, C5, Pz, T4, and T3 on the scalp. The latter were
      referred either to an extracranial electrode or to Fz. In five subjects an
      artificial dipole was set at three different positions on the eyebrow and records
      were taken from the same derivations on the scalp to study the distribution of
      fields of known intensity originating from known locations. It was found that R1
      could be easily detected from all scalp locations. According to its scalp
      distribution, three patterns were identified, which matched those of the
      artificial dipole. Conversely from what had been believed by previous authors,
      the amplitude of R1 could be larger on the contralateral scalp, according to the
      reference used or to the location of its origin. Therefore, it is remarked that
      larger amplitude contralateral to the stimulus cannot anymore be considered an
      exclusive feature of responses arising from the cortex. The evidence we have
      provided recommends a highly cautious approach in interpreting results describing
      trigeminal scalp responses in the latency range of R1.

PMID- 8576393
TI  - Somatosensory evoked potentials elicited by intraneural microstimulation of
      afferent nerve fibers.
AB  - Cortical somatosensory evoked potentials (SEPs) after intraneural
      microstimulation (IMS) of cutaneous and afferent muscle nerve fibers in the
      median nerve were recorded to study the contribution of different afferent fiber
      groups to the SEP. Thirty-seven cutaneous fiber bundles, 10 afferent muscle nerve
      fiber bundles, and 45 single mechanoreceptive afferents of FA I- (n = 12), FA II-
      (n = 8), SA I- (n = 13), and SA II-type (n = 12) were studied in 29 healthy
      subjects. IMS of cutaneous fiber bundles evoked cortical responses corresponding
      to the N20 component after median nerve stimulation in 86% of the fascicles
      studied, whereas IMS of muscle nerve fiber bundles elicited responses only in
      20%. After IMS of single mechanoreceptive afferents of FA I-, FA II-, and SA I
      type cortical responses were obtained in all groups in approximately 80% of the
      stimulated units. The latencies of the SEPs evoked by IMS were comparable to that
      after compound median nerve stimulation (mean difference 0.58 ms). The N20
      amplitudes of SEPs after IMS of cutaneous fiber bundles were on average 28% (n =
      32) and for single afferents 22% (n = 30) of that after compound nerve
      stimulation. It is concluded that the median nerve SEPs evoked by compound median
      nerve stimulation of the resting hand are dominated by cutaneous rather than
      muscle afferent input. Furthermore, the fact that selective stimulation of only a
      few cutaneous afferents produces cortical SEPs of rather high amplitude is
      compatible with the view that sensory information produced by selective afferent
      stimulation is differentially gated into the somatosensory cortex.

PMID- 8576395
TI  - Technology and equipment review. Computerized electronystagmographs.

PMID- 8576396
TI  - Special issue: Cognition, behavior and causality.

PMID- 8576397
TI  - Comments on the crusade against the causal efficacy of human thought.
AB  - Hawkins reiterates the familiar behavioristic doctrine that psychology should
      banish factors that cannot be directly observed. He seems to be unaware that the
      very operant theory he is espousing is heavily invested in internal determinants
      that do not lend themselves to direct observation. Because behavior is often
      unaffected by its immediate situational antecedents and consequences, operant
      analysts are turning increasingly to internalized determinants of behavior, such
      as the residues of past reinforcements. These internalized determinants are not
      directly observable or measurable. They are inferred organismic states. Hawkins
      invokes the standard behavioristic arguments that, like other cognitive events,
      beliefs of personal efficacy are epiphenomenal by-products of conditioned
      responses. The paradigms used to verify the causal contribution of efficacy
      beliefs to performance renders this claim empirically baseless. Efficacy beliefs
      are systematically raised to differential levels by means that involve no
      performances or by bogus feedback that is either unrelated to performance or is
      contrary to performance. In none of these paradigms are instated efficacy beliefs
      reflections of performance, but they are uniformly good predictors of subsequent
      performance. Epiphenomenal assertions are self-destruct arguments.

PMID- 8576398
TI  - Higher-order behavior classes: contingencies, beliefs, and verbal behavior.
AB  - The concepts of reinforcement and of higher-order classes of behavior are
      reviewed and applied to analyses of self-reinforcement, self-efficacy, the causal
      status of private events, and the role of verbal behavior in human action. The
      analyses support the case that Bandura's criticisms of behavior analytic thought
      rest upon several misunderstandings, the most important of which are the
      distinctions between theories and phenomena and a neglect of the process of
      ontogenic selection. Bandura's persistence in promoting these misunderstandings
      is puzzling, because over a period of at least two decades he has repeated
      without substantial correction arguments that were refuted at the time he first
      made them. Bandura's views on these concepts can be interpreted as a contemporary
      variety of creationism in behavioral science.

PMID- 8576399
TI  - Understanding cognition, choice, and behavior.
AB  - Bandura (1995) suggests that a "crusade against the causal efficacy of human
      thought" exists. The present paper disputes that claim, suggesting that the quest
      which does exist involves an understanding of self-efficacy. Examined are
      Bandura's shifting definitions of self-efficacy, his misunderstandings of others'
      work, and implications of some of his attempts to defend the construct. In the
      remainder of the paper Rotter's Social Learning Theory is discussed as a model of
      human choice behavior which recognizes the contributions of both cognitive and
      behavioral traditions within psychology, and has proven to be of great heuristic
      value.

PMID- 8576400
TI  - On the battle between behavior and cognition: lessons from physicists and
      pragmatists.
AB  - Despite several decades of empirical research that has supported the utility of
      cognitive research and therapy, behaviorists continue to battle with cognitivists
      on epistemological grounds. Therefore, I seek to resolve this battle by reviewing
      epistemological lessons learned from two other disciplines, Physics and
      Pragmatism. Paradigm shifts in Physics taught us that formal models of phenomena
      and causality have just as valuable a role in a science of human behavior as
      models based on efficient cause and direct observation. Cognitive models have
      proven their worth as formal models of psychology. Pragmatism has taught us that
      accountability--to the researcher and theorist, to the clinical professional, and
      to the consumer of care--needs to be a renewed value in evaluating psychological
      models. Carefully controlled empirical research has shown cognitive models to
      have ably met these goals. Therefore, cognition meets epistemological criteria,
      other than those touted by behaviorists, which commend it as an important model
      for human psychology.

PMID- 8576401
TI  - A bigger picture: cause and cognition in relation to differing scientific
      frameworks.
AB  - The exchange between Lee (1992) and Hawkins (1992) on the one hand and Bandura
      (present volume) on the other represents a far more fundamental disagreement than
      whether behavior-analytic or cognitive accounts of self-efficacy are more
      persuasive. The deeper disagreement is really a conflict between equally
      legitimate but incompatible world views and, thus, it is both ontological and
      epistemological in nature. The present paper argues that the disagreement can be
      traced to differences between mechanistic and contextual or relational scientific
      frameworks and involves such issues as basic scientific objectives, units of
      analysis, and differing perspectives on causation and explanation. These
      differences are briefly described.

PMID- 8576402
TI  - Cognitive causal mechanisms in human agency: etic and emic considerations.
AB  - The debate over the contribution of cognitive processes in understanding human
      endeavor rages on in psychology despite decades of conceptual and empirical
      scrutiny from researchers. Recently, the construct of self efficacy has
      stimulated a renewal of this debate. We discuss the significance of this
      cognitive construct from the perspective of cross-cultural behavior. We examine
      the empirical evidence from a number of cross-cultural studies, and we argue that
      the etic quality of this construct provides strong evidence for its significance
      in understanding universal aspects of behavior.

PMID- 8576403
TI  - Mind is back in control of pavlovian and skinnerian responses: was it ever away?
AB  - Introspections, anecdotes, mnemonics, and observations of large animals like us
      can only be adequately described in the mapping language of the mind/brain
      delineated by renaissance philosophers--time, space, sensations and reflections.
      But modern behaviorists, confused by this richness, sought clarification by
      adhering strictly to narrow paradigms, excluding the mind/brain, and inventing
      recondite neologisms. The cognitive map underground survived the behavioral
      storms. And psychology, the study of the mind/brain in all its wonders, is
      flourishing once again in respectability.

PMID- 8576404
TI  - Self-efficacy: a cause of debate.
AB  - In response to a paper (Hawkins, 1992) arguing that self-efficacy is a predictor
      but not a cause of behavior, Bandura (1995) has raised a series of counter
      arguments. None of these counter arguments seem sufficient to retreat from the
      claim that self-efficacy is not a true cause of behavior. The present paper
      reaffirms the position that self-efficacy is a useful concept when used as a
      descriptive metaphor. Examples from applied psychology are raised to justify this
      position. Discourse analysis is introduced as one approach which is able to
      circumvent the debate about the reality or nonreality of mental entities.

PMID- 8576405
TI  - The role of cognition in complex human behavior: a contextualistic perspective.
AB  - Cognitive and behavioral psychology have long debated the merits of cognitive
      causality in the explanation of human behavior. We argue, however, that cognitive
      causality must be understood in the context of the pre-analytic philosophical
      assumptions of the scientist, not merely as an empirical matter. Many of the
      issues that seemingly separate cognitive from behavioral positions cannot be
      answered by research. We briefly present Relational Frame Theory, which is a
      behavioral approach to language and cognition. RFT is not subject to the same
      criticisms made by Bandura of behavior analytic thinking. Finally, we describe
      some aspects of Acceptance and Commitment Therapy as an example of the applied
      implications of this contextual analysis of cognition.

PMID- 8576406
TI  - Causation and complexity: old lessons, new crusades.
AB  - A body of experimental work performed by Israel Goldiamond and his colleagues
      over 30 years ago is used to help define the evidential problems raised for
      inferences concerning the causal efficacy of human thought. This work suggests
      that matches of public indicator responses of inferred private rules or states to
      experimenter score sheets may be considered only as weak evidence for causality.
      Further, the problems of inferring causality raised by Wittgenstein's skeptical
      challenge, and its implications for investigating the role of human thought in
      determining human behavior, are briefly described. A selectionist approach, which
      is currently being used by biobehavioral scientists to investigate the behavioral
      complexity which concerns Bandura (this issue) and others, is suggested as one
      way to study the role of private events in human behavior.

PMID- 8576407
TI  - Comparing the incommensurable: where science and politics collide.
AB  - Arguments about the possibility that cognitive variables may play a causal role
      in human behavior are unlikely to be resolved in favor of one side or the other,
      because they set against each other two incommensurable views of human agency.
      Contemporary cognitive models of psychology are based on an implicitly dualist
      view of human behavior, assuming the existence of a nonmaterial mental realm
      which has the capacity to act on the material world. Critics, by comparison,
      frequently argue from an epiphenomenalist position. While there may be sound
      scientific reasons for rejecting self-efficacy theory, and particularly for
      rejecting the utility of the concept that behavior is caused by efficacy
      expectations, this paper argues that epistemic criteria are frequently less
      important than a sense that a theory is compatible with a particular world view.
      I argue that cognitive theories are accepted by the psychological mainstream
      because their dualist basis accords with deeply held cultureal beliefs about the
      relationship between the person and the world. However, the social and political
      consequences of such models are rarely articulated, and there is a need for
      psychologists to develop a more explicit understanding of the relationship
      between psychological theories and their broader implications.

PMID- 8576408
TI  - Beyond determinism and materialism, or isn't it time we took consciousness
      seriously?
AB  - This essay argues: (1) that the fundamental conflict between the behaviorist and
      cognitive approaches to psychology are philosophical, not scientific; (2) that
      the philosophical premises underlying behaviorism (materialism, epiphenomenalism,
      functional model of causality, and the rejection of concepts referring to
      conscious states and processes) are false; and (3) that an objective, scientific
      approach to psychology must take consciousness and volition as axiomatic starting
      points.

PMID- 8576409
TI  - Cognition and causation in human experience.
AB  - Arguments that thoughts cannot have the power to cause or influence behavior are
      briefly addressed. Despite being couched in traditional behavioristic
      terminology, some of these arguments actually invoke the very dualism that they
      criticize. Likewise problematic are portrayals of scientific activity as being
      necessarily grounded in an ontology of physical extension and an epistemology
      that grants the visual system (and hence observability) sole and supreme
      authority. Contemporary cognitivists challenge classical mind-body dualism and
      refer to thoughts and other "mental" phenomena as activities of the living
      system. Three conclusions are drawn: (1) humans think, (2) human thinking
      influences human behavior, and vice-versa, and (3) dialogues on this topic would
      be well served by a refinement of the questions under consideration.

PMID- 8576410
TI  - Cognition and causality, fiction and explanation.
AB  - The debate about the causal efficacy of cognition involves two overlapping but
      different issues: (1) whether explanatory fictions improve upon the power and
      utility of nonfictional explanations of behavior, and (2) whether any
      explanation, either purely empirical or purely inferential, can describe proximal
      causality in behavioral functioning. The resolution of the first issue depends on
      the purpose to which the explanation is to be put. The resolution of the second
      issue depends on the larger paradigmatic context in which causality is
      understood. In modern biosystemic models of behavior, linear causality is
      important only as a special case of the multidirectional and reciprocal causality
      which characterizes complex self-regulating systems.

PMID- 8576411
TI  - Visual feedback in treatment of residual phonological disorders.
AB  - The use of visual biofeedback in the treatment of individuals who have Residual
      Phonological Errors is discussed. This type of treatment was used with clients
      who had not improved through traditional auditory/production based treatments.
      Biofeedback is conceptualized as a cognitive treatment that requires the client's
      analysis of visual information. The information is used in developing correct
      productions of Residual Phonological Errors. The reported results indicate that
      visual feedback is a viable alternative treatment for those who have been unable
      to develop correct sound production through traditional methods.

PMID- 8576412
TI  - Electropalatography in the treatment of articulation/phonological disorders.
AB  - Treatment using electropalatography (EPG) is described. Speech learners wear a
      custom-made appliance called a pseudopalate in order to view their tongue-to
      palate (lingual palatal) contacts on a computer monitor. The results from studies
      with children who have either articulation or phonology-based problems are
      discussed. Assessments of contact patterns used by articulation-impaired children
      suggests that they may produce more atypical articulatory contacts than are noted
      perceptually. Remediation, using electropalatography, showed that the children
      benefited from learning new articulatory gestures rather than learning to correct
      isolated errors. Studies with phonologically-impaired children have shown that
      perceptually neutralized (or non-contrasted) sounds may actually be produced with
      consistent articulatory contrasts. This knowledge could assist in identifying
      sounds that might soon emerge and be more responsive to therapy. Training studies
      with phonologically-impaired children have shown that a motor approach using
      sound contrasts to teach a phonetic inventory is an effective way to assist these
      children. Considerations for candidacy for EPG training are also discussed.

PMID- 8576413
TI  - Speech appliances in the treatment of phonological disorders.
AB  - Some individuals are unable to achieve correct production of the /r/ phoneme
      after receiving substantial amounts of treatment. Clark, Schwarz, and Blakeley
      (1993) developed a removable speech appliance that positions the tongue to
      produce the /r/ phoneme. Their results indicate that the appliance was successful
      with a large group of clients. The rationale and issues related to the use of
      speech appliances are discussed.

PMID- 8576414
TI  - Patterns of transmitter labelling and connectivity of the cat's nucleus of
      Darkschewitsch: a wheat germ agglutinin-horseradish peroxidase and
      immunocytochemical study at light and electron microscopical levels.
AB  - Immunocytochemical studies using antibodies raised against a number of probable
      synaptic transmitters of the mesodiencephalic area, and fibre-tracing studies
      using wheat germ agglutinin-horseradish peroxidase (WGA-HRP), have been performed
      in adult cats. Glutamate and aspartate immunoreactivity produced a strong
      labelling of many cell bodies and terminals in the nucleus of Darkschewitsch
      (ND). gamma-Aminobutyrate (GABA) immunoreactivity in the ND appeared as a
      moderate label in some small neurones, and as a strong label in a few glial-like
      cells, in addition to being present in high levels to produce strong labelling in
      many GABA-immunopositive terminals that possessed pleomorphic vesicles. Some
      choline acetyltransferase-positive terminals and dendrites and a few substance P
      positive fine fibres possessing varicosities also were observed in the ND.
      Following WGA-HRP injection in the ND, dense terminal labelling was seen
      ipsilaterally in the rostral half of the medial accessory olive, suggesting that
      there may be a certain degree of mediolateral and dorsoventral topographic
      correspondance within the ND-olive projection. In the same cases, many cell
      bodies containing HRP reaction product also were found 1) ipsilaterally in the
      motor cortex, anterior pretectal nucleus, and a restricted area of the caudal
      part of the substantia nigra pars reticulata; 2) contralaterally in the anterior
      and posterior interposed cerebellar nuclei as well as in a portion of the lateral
      cerebellar nucleus; and 3) bilaterally in the zona incerta, the posterior
      pretectal nucleus, the pedunculopontine tegmental nuclei, the spinal trigeminal
      nucleus, the dorsal column nuclei, and the spinal cord. Details of the
      interrelationships and functional considerations amongst the ND, adjacent nuclei,
      and longitudinal zones of the cerebellum are discussed.

PMID- 8576415
TI  - Neonatal sensory deprivation induces selective changes in the quantitative
      distribution of GABA-immunoreactive neurons in the rat barrel field cortex.
AB  - Modified activity of the rat vibrissae from birth to adulthood induces profound
      alterations of the responsiveness and selectivity of neurons in the contralateral
      somatosensory barrel field cortex of adult rats. Because these functional
      properties are under the control of the intracortical inhibitory mechanisms, we
      investigated the effects of unilateral removal of face pad vibrissae on the
      quantitative distribution of intracortical gamma-aminobutyric acid (GABA)
      immunoreactive neurons in the rat contralateral and ipsilateral barrel field
      cortices. This distribution was then compared to a population of control animals.
      For the entire cortical depth, no significant changes in the density (7,700/mm3
      vs. 7,400/mm3), proportion (13.6% vs. 14.4%), or size (11.7 microns vs. 12.5
      microns) of GABA-immunoreactive neurons were found in the left contralateral vs.
      the right ipsilateral barrel field cortex. However, in cortical layer IV,
      contralateral to the deprivation, the density and proportion of GABA
      immunoreactive neurons were lower (6,300/mm3 vs. 13,900/mm3, 6.0% vs. 13.6%; P <
      0.01), and these neurons were larger (mean projected height of 15.1 microns vs.
      10.8 microns; P < 0.01) than in the ipsilateral barrel field cortex, suggesting a
      specific loss of GABA expression in a subpopulation of small intracortical
      neurons. In addition to changes in the contralateral layer IV, GABA
      immunoreactive neurons located in the ipsilateral granular layer were also
      affected. Indeed, their numerical density (13,900/mm3) and proportion (13.6%)
      were higher (P < 0.01) than in both hemispheres of control animals (average of
      10,050/mm3 and 9.4%). On the other hand, GABA-immunoreactive neurons in the
      ipsilateral layer V were less numerous (5,600/mm3, 15.0%) than in both sides of
      the controls (average of 10,300/mm3, 22.0%; P < 0.01). Thus, our results show
      that a unilateral sensory deprivation induces highly selective changes in the
      intracortical GABA inhibitory circuitry of both hemispheres. These changes are
      located directly at the input of thalamic afferents and at an output layer of
      corticofugal and commissural axons and could result in a profound reorganization
      of the excitatory and inhibitory drives of both sides of the sensory-deprived
      barrel field cortex.

PMID- 8576416
TI  - Age and sex do not affect the volume, cell numbers, or cell size of the
      suprachiasmatic nucleus of the rat: an unbiased stereological study.
AB  - The circadian rhythms displayed by numerous biological functions are known to be
      sex specific and affected by aging. It has not been settled yet whether the sex-
      and age-related characteristics of circadian rhythms derive from changes in the
      anatomy of the suprachiasmatic nucleus. To shed light on these issues, we applied
      unbiased stereological techniques to estimate the volume of the suprachiasmatic
      nucleus as well as the total number of its cells and the mean volume of their
      somata and nuclei in progressively older groups of male and female Wistar rats
      (aged 1, 6, 12, 18, 24, and 30 months). The volume of the nucleus was estimated
      with the Cavalieri principle on serial sections. The total numbers of neurons and
      astrocytes were estimated by applying the optical fractionator, and the mean
      somatic and nuclear volumes of cells were estimated by using isotropic, uniform
      random sections and the nucleator method. On average, the volume of the
      suprachiasmatic nucleus was 0.044 mm3, and the total number of neurons and
      astrocytes was 17,400. Cells of the dorsomedial and ventrolateral components of
      the nucleus, which are morphologically different, have identical mean perikaryal
      and nuclear volumes, which we estimated to be 750 microns3 and 400 microns3,
      respectively. We further demonstrated that, at all ages analysed, the volume of
      the suprachiasmatic nucleus, the total cell number, and the mean somatic and
      nuclear volumes of its cells are affected neither by the age nor by the sex of
      the animal, regardless of the presence of sex- and age-related variations in
      circadian rhythms. However, the possibility that females may display changes in
      the volume of the suprachiasmatic nucleus at older ages cannot be ruled out. No
      effect of aging was observed in the total number of neurons or in the total
      number of astrocytes.

PMID- 8576417
TI  - Morphology and distribution of microglial cells in the young and adult mouse
      cerebellum.
AB  - The morphology and distribution of microglial cells were studied in the normal
      cerebellum of young and adult mice using the histochemical demonstration of
      nucleoside diphosphatase as a specific microglial marker. Our results showed that
      microglial cells were present in all cerebellular lobules of both young and adult
      mice, but their distribution and morphology were not homogeneous throughout the
      cerebellum. Heterogeneity in microglial cell distribution was exclusively related
      to their location in the different histological layers, and no significant
      differences were found either between the different cerebellar lobules or between
      young and adult mice. Microglial density was higher in the cerebellar nuclei than
      in the cortex; within the cortex, the molecular layer was less densely populated
      by microglial cells than the granular layer and the white matter. The
      morphological study revealed that microglial cells were ramified in all
      cerebellar lobules of both young and adult mice but showed different sizes and
      ramification patterns as a function of their specific location in the different
      histological layers. Several typologies of microglial cells were described on the
      basis of observations in both horizontal and coronal sections. The specific layer
      related pattern of microglial distribution and morphology in mouse cerebellum
      strongly suggests a physical and functional adaptation of these cells to the
      characteristics of their microenvironment.

PMID- 8576418
TI  - Ultrastructure of the synaptic terminals of the dorsal giant serotonin-IR neuron
      and deutocerebral commissure interneurons in the accessory and olfactory lobes of
      the crayfish.
AB  - The olfactory and accessory lobes in the crayfish are large spherical neuropils
      found on each side of its brain. The olfactory lobes receive the afferent axons
      of chemoreceptors that are located along the outer branches of the biramous first
      antennae. The accessory lobes receive a large input from interneurons whose axons
      lie in the deutocerebral commissure. A pair of large serotonergic neurons (the
      dorsal giant neurons) branch unilaterally in the accessory and olfactory lobes of
      each side. From physiological recordings, it has been proposed that the
      deutocerebral commissure interneurons synapse with elements in the accessory
      lobes that in turn connect to the dorsal giant neuron. It has also been proposed
      that the dorsal giant neuron is activated by inputs in the accessory lobe and
      that its output is in the olfactory lobe. This ultrastructural study tests this
      hypotheses by examining the polarity of synaptic terminals on dorsal giant
      neurons and deutocerebral interneurons that have been filled with neurobiotin. In
      double-labelled preparations, we found the deutocerebral interneurons to be
      presynaptic to elements in the accessory lobes, but none of these postsynaptic
      elements was identifiable as the dorsal giant neuron. The dorsal giant neurons
      receive many more synaptic inputs in the accessory lobes than in the olfactory
      lobe. Very few giant serotonin neuron output synapses were found in either lobe.

PMID- 8576419
TI  - Modulation of neurotransmitter receptors following unilateral L1-S2
      deafferentation: NK1, NK3, NMDA, and 5HT1a receptor binding autoradiography.
AB  - Following surgical deafferentation of the spinal cord, cut dorsal roots
      degenerate, and spared projections compensate for this loss by collateral
      sprouting (reactive reinnervation). Light microscopic immunocytochemistry has
      shown sprouting by selected undamaged intraspinal projections, including those
      that express the transmitters substance P and serotonin. Quantitative
      immunoelectron microscopy supports these results by demonstrating loss and
      subsequent recovery of substance P-containing terminals and an increase in
      serotonin-containing terminals. To test the hypothesis that changes in afferent
      innervation modulate neurotransmitter receptors on second-order neurons, we used
      receptor binding autoradiography in this model. Adult rats were subjected to L1
      S2 unilateral dorsal rhizotomy and killed at 1, 2, 6, or > 20 weeks after
      surgery. Receptor binding densities of tachykinin (neurokinins-1 and -3),
      glutamate (N-methyl-D-aspartate), and serotonin (serotonin-1a) receptors were
      assayed in the lumbar dorsal horn. Neurokinin-1 binding density was increased in
      lamina II of the deafferented side by 1 week after surgery, remained elevated at
      2 weeks, and returned to control values by 6 weeks. Neurokinin 3 binding density
      was elevated at 2 weeks and then returned to control levels. N-methyl-D-aspartate
      receptor binding showed slight but not statistically significant increased
      binding density at 6 and at > 20 weeks. No significant changes were found in
      serotonin-1a receptor binding density. The elevations in tachykinin receptor
      binding density occur when afferents in the dorsal horn are degenerating and
      suggest reactive up-regulation of the receptor. The return to normal levels
      coincides with reactive reinnervation in the spinal cord, which restores synaptic
      numbers. Changes in N-methyl-D-aspartate binding occur much later than the
      restitution of synaptic numbers but may indicate a role for this receptor in
      synaptic stabilization following reactive reinnervation.

PMID- 8576420
TI  - Sound stimulation induces Fos-related antigens in cells with common morphological
      properties throughout the auditory brainstem.
AB  - Cells within the auditory brainstem of cat that respond to sound by producing the
      transcription factor Fos or related proteins were identified by immunostaining
      with antisera against Fos and Zif/268. Within the cochlear nucleus, all antisera
      showed similar staining patterns, however, in the superior olive and inferior
      colliculus, staining patterns differed between antisera. Immunostained cells were
      characterized by their size, location, by the presence of perisomatic terminals
      that immunostained for glutamate decarboxylase or synaptophysin, or by electron
      microscopy. Most cell classes were not immunopositive. In the ventral cochlear
      nucleus, roughly 99% of Fos-positive cells had few perisomatic terminals. Within
      the superior olivary complex (SOC), the majority of immunopositive cells had few
      perisomatic terminals. Lateral olivocochlear cells were identified as Fos
      positive by their size, location, lack of perisomatic terminals, and positive
      costaining for acetylcholinesterase as evidenced by a novel reaction product.
      This report appears to be the first demonstration of these cells responding to
      sound stimulation. Within the inferior colliculus, bands of positive cells
      produced by tonal stimulation extended from the central nucleus throughout the
      dorsal cortex and the posterior pericentral region, a finding unexpected on the
      basis of previous electrophysiological recordings and anatomical studies of
      ascending inputs to the colliculus. Approximately 35% of Fos-positive cells in
      the inferior colliculus had plentiful perisomatic terminals. Results demonstrate
      a high degree of specificity of auditory cell types that respond to sound by
      producing Fos-like proteins and show that previously intractable physiological
      questions can be addressed by assaying for sound-induced production of these
      antigens.

PMID- 8576421
TI  - Projections of ankle joint afferents to the spinal cord and brainstem of the
      chicken (Gallus g. domesticus).
AB  - The projections of the ankle joint capsule afferents were studied by
      transganglionic transport of horseradish peroxidase injected directly into the
      ankle joint. The number and size of the labelled dorsal root ganglion cells were
      measured from synsacral nerves 2-9. In the dorsal root ganglia, all sizes of
      sensory neurones were labelled, and the largest number of labelled cells was in
      ganglia 5-7. The extensive sympathetic innervation of the ankle joint was
      identified by the large number of cell bodies labelled in the sympathetic ganglia
      of the paravertebral chain. Labelled afferent fibres projected to the spinal cord
      from the 2nd to the 8th synsacral nerves, with the rostral projection mainly via
      Lissauer's tract and the dorsal funiculus. Terminal labelling in the dorsal horn
      was identified in laminae I-III and VI, with a slight projection to V. Two areas
      of dense labelling, which did not correspond with the largest number of labelled
      dorsal root ganglion cells, were identified. A rostral area with the highest
      density of label was observed at the level of synsacral nerves 3-4 and a second
      slightly less dense area between synsacral nerves 7-8. In the caudal medulla,
      diffuse terminal labelling was observed in the nucleus gracilis et cuneatus,
      nucleus of the tractus solitarius, and the nucleus cuneatus externus. These
      results are discussed in a comparative context to identify similarities and
      differences between different primary afferent projections in birds and mammals
      and to highlight the possible functional significance of the avian articular
      afferent projection.

PMID- 8576422
TI  - Type 1 interleukin-1 receptor in the rat brain: distribution, regulation, and
      relationship to sites of IL-1-induced cellular activation.
AB  - Systemic interleukin-1 (IL-1) activates the hypothalamo-pituitary-adrenal (HPA)
      axis, an effect exerted through increased synthesis and secretion of
      corticotropin-releasing factor (CRF) by parvicellular neurosecretory neurons. The
      site(s) and mechanism(s) through which circulating IL-1 may access central
      systems governing HPA axis output remain obscure. To identify potential cellular
      targets for blood-borne IL-1, we analyzed the distribution of mRNA encoding the
      rat type 1 IL-1 receptor (IL-1R1) in rat brain. Regional ribonuclease protection
      assays detected a single protected fragment corresponding to the membrane-bound
      form of the IL-1R1 mRNA in all areas analyzed. In situ hybridization revealed
      labeling predominantly over barrier-related cells, including the leptomeninges,
      non-tanycytic portions of the ependyma, the choroid plexus, and vascular
      endothelium. Low to moderate levels of the IL-1R1 mRNA were detected in just a
      few neuronal cell groups, including the basolateral nucleus of the amygdala, the
      arcuate nucleus of the hypothalamus, the trigeminal and hypoglossal motor nuclei,
      and the area postrema. No specific labeling for IL-1R1 mRNA was detected over
      neurons that respond to intravenous IL-1 beta by induction of transcription
      factor Fos, including hypophysiotropic CRF cells and brainstem catecholamine
      neurons. Injection of IL-1 beta did, however, provoke induction of mRNA encoding
      the immediate-early gene, NGFI-B, but not c-fos, in two major loci of IL-1R1
      expression, vascular endothelial cells, and the area postrema. Intravenous
      injection of IL-1 beta acutely down-regulated IL-1R1 mRNA in perivascular cells,
      but not in neuronal cell groups. These results suggest the parenchymal sites of
      IL-1R1 expression in rat to be distinct from those reported previously in mouse.
      The common expression in both species of an IL-1R in non-neuronal elements
      highlights the possibility that IL-1-mediated activation of CRF neurons may
      result from cytokine-receptor interaction at vascular, and/or other barrier
      related, sites to trigger release of secondary signalling molecules in a position
      to interact with components of HPA control circuitry.

PMID- 8576423
TI  - Proportions and structure of contacting and non-contacting varicosities in the
      perivascular plexus of the rat tail artery.
AB  - Most sympathetic postganglionic noradrenergic varicosities of the perivascular
      plexus of small muscular arteries in laboratory mammals make contact with the
      outer smooth muscle cells of the media at neuromuscular junctions. These
      neurovascular junctions have most of the characteristics of those in skeletal
      muscle. In the rat tail artery, which bears a particularly dense perivascular
      plexus, many studies indicate that both purinergic and noradrenergic mechanisms
      underlie neurally mediated vasoconstriction. We have examined the relationship of
      large axonal varicosities to the smooth muscle surface of proximal parts of this
      vessel using three-dimensional reconstructions from serial thin sections
      photographed in the electron microscope. Unlike in small arterioles, less than
      50% of the large photographed in the electron microscope. Unlike in small
      arterioles, less than 50% of the large varicosities lying within 1 micron of the
      outer surface of this artery were found to make neuromuscular junctions. In some
      non-contacting varicosities, accumulations of synaptic vesicles were aggregated
      toward axonal membrane which was bare of Schwann cell toward the vessel surface.
      Prejunctional membrane specializations were detected at 20% of contacting and 12%
      of non-contacting varicosities. All of the latter lay close (< 350nm) to the
      smooth muscle. These anatomical data suggest that, in the rat tail artery,
      transmitter release by exocytosis may occur from both types of varicosity.

PMID- 8576424
TI  - Dopamine in the lobster Homarus gammarus: II. Dopamine-immunoreactive neurons and
      development of the nervous system.
AB  - Dopamine-immunoreactive neurons were revealed in lobster embryos, larvae, and
      postlarvae, and staining patterns were compared to neuronal labeling in the
      juvenile lobster nervous system (Cournil et al. [1994] J. Comp. Neurol. 344:455
      469). Dopamine immunoreactivity is first detected by midembryonic life in 35-40
      neuronal somata located anteriorly in brain and subesophageal ganglion. When the
      lobsters assume a benthic life during the first postlarval stage, an average of
      58 cell bodies are labeled. The acquisition of dopamine in lobster neurons is a
      protracted event spanning embryonic, larval, and postlarval life and finally
      reaching the full complement of roughly 100 neurons in juvenile stages. Some of
      the dopaminergic neurons previously identified in the mature nervous system, such
      as the paired Br cells, L cells, and mandibular cells, are labeled in embryos and
      persist throughout development. In contrast, other neurons stain transiently for
      dopamine during the developmental period, but, by the adult stage, these neurons
      are no longer immunoreactive. Such transiently labeled neurons project to the
      foregut, the thoracic dorsal muscles, the neurohormonal pericardial plexus, and
      the pericardial pouches. It is proposed that these neurons are alive and
      functioning in adult lobster but that dopamine levels have been abolished,
      providing that neurotransmitter status is a dynamic, changing process.

PMID- 8576425
TI  - Neurochemical phenotype of corticocortical connections in the macaque monkey:
      quantitative analysis of a subset of neurofilament protein-immunoreactive
      projection neurons in frontal, parietal, temporal, and cingulate cortices.
AB  - The neurochemical characteristics of the neuronal subsets that furnish different
      types of corticocortical connections have been only partially determined. In
      recent years, several cytoskeletal proteins have emerged as reliable markers to
      distinguish subsets of pyramidal neurons in the cerebral cortex of primates. In
      particular, previous studies using an antibody to nonphosphorylated neurofilament
      protein (SMI-32) have revealed a consistent degree of regional and laminar
      specificity in the distribution of a subpopulation of pyramidal cells in the
      primate cerebral cortex. The density of neurofilament protein-immunoreactive
      neurons was shown to vary across corticocortical pathways in macaque monkeys. In
      the present study, we have used the antibody SMI-32 to examine further and to
      quantify the distribution of a subset of corticocortically projecting neurons in
      a series of long ipsilateral corticocortical pathways in comparison to short
      corticocortical, commissural, and limbic connections. The results demonstrate
      that the long association pathways interconnecting the frontal, parietal, and
      temporal neocortex have a high representation of neurofilament protein-enriched
      pyramidal neurons (45-90%), whereas short corticocortical, callosal, and limbic
      pathways are characterized by much lower numbers of such neurons (4-35%). These
      data suggest that different types of corticocortical connections have
      differential representation of highly specific neuronal subsets that share common
      neurochemical characteristics, thereby determining regional and laminar cortical
      patterns of morphological and molecular heterogeneity. These differences in
      neuronal neurochemical phenotype among corticocortical circuits may have
      considerable influence on cortical processing and may be directly related to the
      type of integrative function subserved by each cortical pathway. Finally, it is
      worth noting that neurofilament protein-immunoreactive neurons are dramatically
      affected in the course of Alzheimer's disease. The present results support the
      hypothesis that neurofilament protein may be crucially linked to the development
      of selective neuronal vulnerability and subsequent disruption of corticocortical
      pathways that lead to the severe impairment of cognitive function commonly
      observed in age-related dementing disorders.

PMID- 8576426
TI  - Metabotropic glutamate receptor mGluR5 subcellular distribution and developmental
      expression in hypothalamus.
AB  - The metabotropic glutamate receptor mGluR5 is a G-protein coupled receptor that
      plays a key role in release of Ca2+ from internal stores via inositol
      triphosphate mobilization. Western and Northern blot analyses revealed a greatly
      enhanced expression of mGluR5 in rats during early stages of hypothalamic
      development compared with the adult. This enhanced developmental expression
      provides an explanation for the dramatic physiological response of developing
      neurons to metabotropic glutamate receptor activation and supports the argument
      that metabotropic glutamate receptors may play an important role in hypothalamic
      development. During development, expression of the mGluR5 gene was reduced, not
      only in the hypothalamus but also in other regions of the brain. A differential
      decrease in mGluR5 protein was found in different brain regions with Western blot
      analysis. The hypothalamus showed a sixfold decrease in mGluR5 with development,
      whereas the cortex showed only a threefold decrease. Immunocytochemistry with an
      affinity-purified antibody against a peptide deduced from the cloned mGluR5 gene
      revealed selective expression in some regions in the adult hypothalamus. In the
      adult and developing (postnatal day 10) brain, immunoreactive neurons were found
      in the suprachiasmatic nucleus, preoptic area, lateral hypothalamus, and
      mammillary region, areas where the related metabotropic glutamate receptor mGluR1
      is also found. In contrast, the ventromedial nucleus, an area critically involved
      in the regulation of food intake and metabolic balances, showed strong mGluR5
      immunoreactivity but no mGluR1 immunoreactivity. Little or no mGluR5 staining was
      found in the neurosecretory neurons of the paraventricular, supraoptic, and
      arcuate nuclei. Ultrastructurally, mGluR5 was associated with the cytoplasmic
      face of the plasmalemma on hypothalamic dendrites, dendritic spines, and neuronal
      perikarya in the adult. The strongest immunoreactivity was found in patches on
      the membrane, sometimes associated with the postsynaptic side of synapses and
      sometimes associated with nonsynaptic dendritic or perikaryal membrane. Intense
      immunostaining was found on some astrocyte processes surrounding synaptic
      complexes containing asymmetrical synapses. These astrocytes would be in an ideal
      position to receive excitatory signals from glutamatergic axons. Unlike the
      punctate appearance of immunolabeling on neuronal membranes, astrocytes showed
      continuous staining along the plasma membrane.

PMID- 8576428
TI  - Mapping subcortical extrarelay afferents onto primary somatosensory and visual
      areas in cats.
AB  - Projections from the claustrum (Cl) and the thalamic anterior intralaminar nuclei
      (AIN) to different representations within the primary somatosensory (S1) and
      visual (V1) areas were studied using the multiple retrograde fluorescent tracing
      technique. The injected cortical regions were identified electrophysiologically.
      Retrograde labeling in Cl reveals two different projection patterns. The first
      pattern is characterized by a clear topographic organization and is composed of
      two parts. The somatosensory Cl shows a dorsoventral progression of cells
      projecting to the hindpaw, forepaw, and face representations of S1. The visual Cl
      has cells projecting to the vertical meridian representation of V1 surrounded
      dorsally by neurons projecting to the representation of retinal periphery. A
      second pattern of Cl projections is composed of neurons that are distributed
      diffusely through the nucleus. In both somatosensory and visual sectors, these
      intermingle with the topographically projecting cells. Neurons retrogradely
      labeled from cortical injections are always present in the AIN. In the central
      medial nucleus, the segregation of modality is evident: The visual-projecting
      sector is dorsal, and the somatosensory is ventral. Projections from the central
      lateral nucleus display detectable somatotopic and retinotopic organization:
      Individual regions are preferentially connected with specific representations of
      S1 or V1. In the paracentral nucleus, no clear regional preferences are
      detectable. Also performed were comparisons of the proportions of neurons
      projecting to different sensory representations. Projections to V1 from both AIN
      and Cl are biased towards the retinal periphery representation. S1 projection
      preference is for the forepaw representation in Cl and for the hindpaw in the
      AIN. The quantitative analysis of multiply labeled cells reveals that, compared
      to Cl, the AIN contains a higher proportion of neurons branching between
      different representations of S1 or V1. The concept of topographic vs. diffuse
      projecting systems is reviewed and discussed, and functional implications of
      quantitative analysis are considered.

PMID- 8576427
TI  - A quantitative analysis of the dendritic organization of pyramidal cells in the
      rat hippocampus.
AB  - The three dimensional organization of the dendritic trees of pyramidal cells in
      the rat hippocampus was investigated using intracellular injection of horseradish
      peroxidase in the in vitro hippocampal slice preparation and computer-aided
      reconstruction. The total dendritic length, dendritic length in each of the
      hippocampal laminae, and the number of dendritic branches were measured in 20 CA1
      pyramidal cells, 7 neurons in CA2 and 20 CA3 pyramidal cells. The total dendritic
      length of CA3 pyramidal cells varied in a consistent fashion depending on their
      position within the field. Cells located close to the dentate gyrus had the
      smallest dendritic trees which averaged 9,300 microns in total length. Cells in
      the distal part of CA3 (near CA2) had the largest dendritic trees, averaging
      15,800 microns. The CA2 field contained cells which resembled CA3 pyramidal cells
      in most respects except for the absence of thorny excrescences on their proximal
      dendrites. There were also smaller pyramidal cells that resembled CA1 neurons.
      CA1 pyramidal cells tended to be more homogeneous. Pyramidal neurons throughout
      the transverse extent of CA1 had a total dendritic length on the order of 13,500
      microns. The quantitative analysis of the laminar distribution of dendrites
      demonstrated that the stratum oriens and stratum radiatum contained significant
      portions of the pyramidal cell dendritic trees. In Ca3, for example, 42-51% of
      the total dendritic length was located in stratum oriens; about 34% of the
      dendritic tree was located in stratum radiatium. The amount of dendritic length
      in stratum lacunosum-moleculare of CA3 varied depending on the location of the
      cell. Many CA3 cells located within the limbs of the dentate gyrus, for example,
      had no dendrites extending into stratum lacunosum-moleculare whereas those
      located distally in CA3 had about the same percentage of their dendritic tree in
      stratum lacunosum-moleculare as in stratum radiatum. In CA1, nearly half of the
      dendritic length was located in stratum radiatum, 34% was in stratum oriens and
      18% was in stratum lacunosum-moleculare. These studies identified distinctive
      dendritic branching patterns, in the stratum radiatum and stratum lacunosum
      moleculare, which clearly distinguished CA3 from CA1 neurons.

PMID- 8576429
TI  - Comparative ultrastructural localization of the NMDAR1 glutamate receptor in the
      rat basolateral amygdala and bed nucleus of the stria terminalis.
AB  - The N-methyl-D-aspartate (NMDA)-type glutamate receptor in the basolateral
      amygdala (BLA) has been implicated in activity-dependent plasticity important for
      cortically evoked acquisition of fear-potentiated startle response. We examined
      the ultrastructural immunoperoxidase labeling of the R1 subunit of the NMDA
      receptor in the BLA of adult rats to determine the potential cellular and
      subcellular sites mediating the effects generated by NMDA activation. The
      localization was compared with that seen in the bed nucleus of the stria
      terminalis (BNST), the major efferent pathway from the central nucleus of the
      amygdala, which has a more pronounced involvement in autonomic function. Electron
      microscopy established that in the BLA, 68.4% (n = 177) of the profiles showing
      NMDAR1-like immunoreactivity (NMDAR1-LI) were dendrites, and 19.8% were distal
      tips of astrocytic processes. In contrast, profiles containing NMDAR1-LI (n =
      262) in the BNST were more equally distributed between dendrites (37.4%) and
      axons (38.2%). The subcellular localization of NMDAR1 immunoreactivity was,
      however, similar in both regions. Our findings provide the first ultrastructural
      evidence that glutamate may prominently act through NMDAR1 receptors to elicit
      postsynaptic actions on intrinsic neurons in the BLA and BNST. The results also
      indicate that, in the BLA, the NMDAR1 receptor plays an important role in
      astrocytic function, whereas the receptor is more preferentially a presynaptic
      modulator in axons which terminate in or pass through the BNST.

PMID- 8576430
TI  - Differential localization of NMDA and AMPA receptor subunits in the lateral and
      basal nuclei of the amygdala: a light and electron microscopic study.
AB  - Anatomical and physiological studies indicate that the amino acid L-glutamate is
      the excitatory transmitter in sensory afferent pathways to the amygdala and in
      intraamygdala circuits involving the lateral and basal nuclei. The regional,
      cellular, and subcellular immunocytochemical localizations of N-methyl-D
      aspartate (NMDA) and L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      (AMPA), two major classes of glutamate receptors, were examined in these areas of
      the amygdala. A monoclonal antibody and a polyclonal antiserum directed against
      the R1 subunit of the NMDA receptor were used. Each immunoreagent produced
      distinct distributions of perikaryal and neuropilar staining. Dendritic
      immunoreactivity was localized primarily to asymmetric (excitatory) synaptic
      junctions, mostly on spines, consistent with the conventional view of the
      organization and function of NMDA receptors. Whereas the anti-NMDAR1 antiserum
      produced sparse presynaptic axon terminal labeling and extensive glial labeling,
      the anti-NMDAR1 antibody labeled considerably fewer glia and many more
      presynaptic axon terminals. Labeled presynaptic terminals formed asymmetric and
      symmetric synapses, suggesting presynaptic regulation of both excitatory and
      inhibitory transmission. Immunoreactivity for different subunits of the AMPA
      receptor (GluR1, GluR2/3, and GluR4) was uniquely distributed across neuronal
      populations, and some receptor subunits were specific to certain cell types.
      Immunoreactivity for GluR1 and Glu2/3 was predominantely localized to dendritic
      shafts and was more extensive than that of GluR4 due to heavy labeling of
      proximal portions of dendrites. The distribution of GluR4 immunoreactivity was
      similar to NMDAR1: GluR4 was seen in presynaptic terminals, glia, and dendrites
      and was primarily localized to spines. The presynaptic localization of GluR4 in
      the absence of GluR2 suggests glutamate-mediated modulation of presynaptic Ca++
      concentrations. These data add to our understanding of the morphological basis of
      pre- and postsynaptic transmission mechanisms and synaptic plasticity in the
      amygdala.

PMID- 8576431
TI  - Subdivisions of macaque monkey auditory cortex revealed by calcium-binding
      protein immunoreactivity.
AB  - The aim of this investigation was to characterize auditory areas of the primate
      cerebral cortex on the basis of chemoarchitecture. Cortical areas of the
      supratemporal plane were delineated in Macaca fuscata (M. fuscata) by
      immunocytochemical staining for parvalbumin, staining for cytochrome oxidase,
      examination of cyto- and myeloarchitecture, and retrograde tracing of
      corticocortical connections. Comparative observations were made on Macaca
      fascicularis (M. fascicularis). Differential staining of fiber plexuses, probably
      of thalamic origin, identifies a central core zone of dense immunostaining and a
      surrounding zone of moderate-to-dense immunostaining composed of anteromedial,
      lateral, and posteromedial fields. Outside the second zone, there is a third
      anterolateral zone of weaker immunoreactivity, and, outside that zone, there is a
      fourth zone in which immunoreactivity is virtually absent. Differences in
      parvalbumin immunostaining in the auditory fields may reflect differences in
      relative contributions of thalamic inputs from parvalbumin-immunoreactive cells
      in the medial geniculate complex. The central core zone and the surrounding three
      fields can be correlated with major auditory fields previously defined by
      multiunit mapping and thalamocortical connectivity. The core zone contains a
      large principal field and an anterior extension. The pattern of corticocortical
      connections between these and adjoining fields suggests that the anteromedial,
      lateral, and posteromedial fields represent first steps in three streams of
      connections passing outward from auditory into association cortex. M. fuscata has
      an unusually large auditory cortex that is more deeply placed in the lateral
      sulcus in comparison to that of M. fascicularis. A small annectant gyrus provides
      a guide to the position of the primary auditory area.

PMID- 8576432
TI  - Auditory thalamocortical pathways defined in monkeys by calcium-binding protein
      immunoreactivity.
AB  - This study investigated differentiation of Macaca fuscata auditory thalamus into
      chemically defined nuclei forming relays to auditory cortical areas. The thalamus
      was stained immunocytochemically for parvalbumin and 28 kDa calbindin in normals
      and in brains in which retrogradely transported tracers were injected into middle
      layers of auditory cortical areas or applied to the cortical surface. Parvalbumin
      and calbindin-immunoreactive cells show a complementary distribution in ventral,
      anterodorsal, posterodorsal, and magnocellular medial geniculate nuclei. The
      ventral nucleus has a high density of parvalbumin cells and few calbindin cells,
      and the anterodorsal nucleus has a high density of parvalbumin cells and moderate
      numbers of calbindin cells. Both nuclei have a dense parvalbumin-immunoreactive
      neuropil formed by terminations of fibers ascending in the brachium of the
      inferior colliculus. The posterodorsal nucleus has approximately equal
      proportions of parvalbumin and calbindin cells; neuropil staining is weak but
      contains terminations of calbindin-immunoreactive fibers ascending in the
      midbrain tegmentum. The magnocellular nucleus contains domains of parvalbumin and
      calbindin cells. Parvalbumin cells in the ventral nucleus project to a central
      core of auditory cortex with densest parvalbumin immunoreactivity. Those in
      anterodorsal and posterodorsal nuclei project to surrounding auditory fields with
      less dense parvalbumin immunoreactivity; those in the magnocellular nucleus
      project widely to auditory and other fields. Injections of middle cortical layers
      label a large majority of parvalbumin cells in the ventral, anterodorsal, or
      posterodorsal nuclei and in the magnocellular nucleus. Superficial deposits label
      calbindin cells only, usually in more than one nucleus, implying a widespread
      projection system.

PMID- 8576433
TI  - Patchy and laminar terminations of medial geniculate axons in monkey auditory
      cortex.
AB  - The object of this study was to identify the terminal distributions of
      thalamocortical axons arising in chemically characterized subdivisions of the
      medial geniculate complex. Large injections of wheat germ agglutinin-conjugated
      horseradish peroxidase or small injections of Phaseolus vulgaris leucoagglutinin
      were made in the medial geniculate complex of Macaca fuscata. The terminal
      distributions of labeled axons in the cortex were correlated with auditory
      cortical fields demonstrable by different intensities of immunoreactivity for
      parvalbumin. Fibers from the ventral nucleus terminated mainly in layer IV and
      deep portion of layer III (IIIB), with additional terminations in layers I-IIIA
      and in layer VI. In layers IIIB-IV, a major terminal plexus was formed by a small
      number of dense patches, 300-500 microns in diameter, surrounded by smaller
      satellite patches. The patches conformed to a similarly lobulated pattern of
      parvalbumin fiber immunoreactivity. Terminations of some individually labeled
      thalamocortical fibers were restricted to a single patch, whereas others
      innervated more than one patch by collateral branches. Fibers from the dorsal
      nuclei ending in areas of less dense parvalbumin immunoreactivity surrounding the
      primary auditory cortex formed much larger terminal patches centered largely in
      layer IIIB. Fibers from the magnocellular nucleus had relatively few terminal
      branches but innervated extremely wide areas by collaterals of single axons. Two
      types of axons arose from the magnocellular nucleus, one terminating
      preferentially in middle cortical layers and the other exclusively in layer I.
      These may arise respectively from parvalbumin- and calbindin-immunoreactive cell
      populations in the magnocellular nucleus.

PMID- 8576434
TI  - Factors influencing mossy fiber collateral sprouting in organotypic slice
      cultures of neonatal mouse hippocampus.
AB  - Collateral sprouting of dentate granule cell axons, the mossy fibers, occurs in
      response to denervation, kindling, or excitotoxic damage to the hippocampus.
      Organotypic slice culture of rodent hippocampal tissue is a model system for the
      controlled study of collateral sprouting in vitro. Organotypic roller-tube
      cultures were prepared from hippocampal slices derived from postnatal day 7 mice.
      The Timm heavy metal stain and densitometry were used to assay the degree of
      mossy fiber collateral sprouting in the molecular layer of the hippocampal
      dentate gyrus. Factors influencing mossy fiber collateral sprouting were time in
      culture, positional origin of the slice culture along the septotemporal axis of
      the hippocampus, and presence of attached subicular-entorhinal cortical tissues.
      Collateral sprouting in the molecular layer was first detected after 6 days in
      culture and increased steadily thereafter. By 2 weeks considerable sprouting was
      apparent, and at 3 weeks intense sprouting was observed within the molecular
      layer. An intrinsic septal-to-temporal gradient of collateral sprouting was
      apparent at 14 days in culture. To determine whether differential damage to the
      mossy fibers was the basis for the differences in collateral sprouting along the
      septotemporal axis, we made complete transections of the mossy fiber projection
      as it exited the dentate hilus at various levels along the septotemporal axis; no
      differences were found on subsequent collateral sprouting in the dentate
      molecular layer. Timm-stained hippocampal cultures with an attached entorhinal
      cortex, a major source of afferent innervation to the dentate granule cells,
      displayed significantly less collateral sprouting at 10 days in culture compared
      to that in cultures from adjacent sections without attached subicular-entorhinal
      tissues present. Thus, time in culture, position along the septotemporal axis,
      and presence of afferent cortical tissues influence aberrant neurite collateral
      sprouting in organotypic slice cultures of neonatal mouse hippocampus.

PMID- 8576435
TI  - Vasopressin binding in the cerebral cortex of the Mongolian gerbil is reduced by
      transient cerebral ischemia.
AB  - In Mongolian gerbils, the content of vasopressin in the cerebral cortex, the
      striatum, and the hypothalamus is increased after induction of acute cerebral
      ischemia. We used an iodinated vasopressin analogue and light microscopic
      autoradiography to study the distribution of vasopressin V1 receptors in the
      brain of adult male gerbils and to evaluate the effects of a transient bilateral
      cerebral ischemia (6 minutes) on the density of this receptor population. The
      animals were killed immediately or 10, 30, or 100 hours after transient bilateral
      occlusion of the common carotid arteries. In control animals, specific [125I]-VPA
      binding sites were present in various structures of the brain (olfactory bulb,
      anterior olfactory nucleus, lateral septum, bed nucleus of the stria terminalis,
      median preoptic area, ventral pallidum, substantia innominata, amygdala,
      thalamus, hypothalamic mammillary nuclei, superior colliculus, subiculum, central
      gray, nucleus of the solitary tract, hypoglossal nucleus). The strongest labeling
      was detected in the cerebral cortex, layers 5-6. After 30-100 hours of survival
      time following ischemia there was a marked decrease in [125I]-VPA binding site
      density in these cerebral cortex layers. To a lesser degree, a decrease was also
      detected in the lateral septal nucleus. In contrast, labeling in other
      noncortical structures remained unchanged. All animals with 100 hours recovery
      showed a loss of cells in hippocampus (CA1 layer) and striatum. In addition,
      ischemia induced concomitant and proliferative changes in cortical and
      hippocampal astrocytes assessed by glial fibrillary acid protein
      immunoreactivity. These observations indicate a role for vasopressin in the
      cerebral cortex either on neurons or on glial cells and the modulation of
      vasopressin receptor expression by transient cerebral ischemia.

PMID- 8576436
TI  - Morphology and connections of neurons in area 17 projecting to the extrastriate
      areas MT and 19DM and to the superior colliculus in the monkey Callithrix
      jacchus.
AB  - Neurons of area 17, the primary visual cortex, project to various anatomically
      and physiologically different extrastriate areas and subcortical regions. In the
      present investigation, we addressed the question of whether the efferent neurons
      in area 17 can contribute to functional diversity between these regions. We
      approached this question by analyzing the dendritic morphology of neurons in area
      17 projecting to area MT, area 19DM, and the superior colliculus in the new world
      simian primate Callithrix jacchus, because dendritic morphology is an important
      factor in determining physiological properties of nerve cells. Retrograde
      transport of fluorochromes injected into the target regions, and intracellular
      injections of Lucifer yellow in the prelabelled neurons, revealed the following.
      1) Morphologically identical large pyramidal cells in layer VI of area 17 project
      to all three targets. Some of them possess axon collaterals to two or all three
      targets, suggesting that they provide common information to all three areas. 2)
      Pyramidal cells in layer IIIc projecting to area MT form a morphologically
      homogeneous population. 3) Three small to medium-sized pyramidal cell types in
      layers IIIa-c, spiny stellate cells in layer IIIc, and another large pyramidal
      cell type in layer VI project to area 19DM. 4) Pyramidal cells in the lower two
      thirds of layer V in area 17 project to the superior colliculus. In conclusion,
      we have shown that in Callithrix one efferent pathway may originate from several
      cell types. However, with the exception of the large cells in layer VI, efferent
      cells projecting to area MT, area 19DM, and the superior colliculus were
      morphologically distinct. This suggests that functional differences between brain
      regions could arise in part from morphological heterogeneity between and within
      the efferent cell populations.

PMID- 8576437
TI  - Embryonic development of gonadotropin-releasing hormone neurons in the sockeye
      salmon.
AB  - Immunocytochemistry and in situ hybridization were used to test the hypothesis
      that gonadotropin-releasing hormone (GnRH) neurons are formed in the olfactory
      placode during embryonic development in a salmonid, Oncorhynchus nerka. The
      development of GnRH neurons and the pituitary cell types was examined from 19
      through 910 days after fertilization. Immunoreactive GnRH was first detected at
      19 days in the cells of the olfactory placode. GnRH immunoreactivity was not
      detected in any other structure of the central nervous system at this age. By day
      24, GnRH-immunoreactive neurons were seen in the apical, intermediate, and basal
      layers of the olfactory placode. From days 30 through 51, GnRH neurons were seen
      emerging from the epithelium, along the olfactory nerve, and at the rostral
      olfactory bulb. By day 41, GnRH immunoreactivity was lost in the nasal
      epithelium. In the 72-day-old fish, most of the GnRH neuronal population was
      found in ganglia of the nervus terminalis, at the cribriform bone (gCB), and at
      the rostral olfactory bulb (gROB). On day 293, a decrease in GnRH-immunoreactive
      neurons in the gCB and gROB was concomitant with an initial appearance of GnRH
      immunoreactive neurons and fibers along the caudoventral olfactory bulb. By day
      462, the distribution of GnRH neurons and fibers was almost similar to adults. In
      maturing adults (910 days), GnRH-immunoreactive neurons were rarely seen in the
      nasal regions, but were primarily found in the basal forebrain. GnRH fibers were
      widespread in the brain, proximal para distalis, and in the pars intermedia of
      the pituitary. Our study supports the notion that neurons expressing salmon-GnRH
      mRNA and peptide originate in the medial olfactory placode and migrate into the
      basal forebrain during development. The midbrain neurons did not express salmon
      GnRH mRNA or peptide in the larval and juvenile fish.

PMID- 8576438
TI  - Evidence for muscarinic acetylcholine receptor subtypes in the pigeon
      telencephalon.
AB  - At least five subtypes of muscarinic acetylcholine receptors are expressed in
      various mammalian tissue preparations. The following experiment, through the use
      of direct binding assays (using tritiated quinuclidinyl benzilate), competitive
      binding assays (using tritiated quinuclidinyl benzilate and unlabeled pirenzepine
      or AF-DX 116), and autoradiographic techniques, examined whether two of these
      five putative muscarinic acetylcholine receptor subtypes can be found in avian
      brain. Accordingly, autoradiographic mapping of pirenzepine-sensitive (M1-like)
      and AF-DX 116-sensitive (M2-like) muscarinic acetylcholine receptor subtypes in
      the pigeon telencephalon was conducted. Although both ligands bound throughout
      the brain, most telencephalic regions, including the archistriatum, the
      neostriatum, and basal ganglia structures like lobus paraolfactorius, nucleus
      accumbens, and paleostriatum, showed a higher density of M1-like sites. The
      exception to this finding was the nucleus basalis which appeared as a region
      where M2-like sites predominated. Moreover, the telencephalic region with the
      largest ratio of M1-like to M2-like sites was the lateral portion of the
      parahippocampus; a characteristic shared with the mammalian dentate gyrus. The
      findings reported here are generally consistent with previous reports of
      mammalian M1/M2 receptor distributions.

PMID- 8576439
TI  - Permanent neuronal cell loss in the cerebellum of rats exposed to continuous low
      blood alcohol levels during the brain growth spurt: a stereological
      investigation.
AB  - This study demonstrates that exposure to an alcohol regimen that resulted in low,
      uniform blood alcohol concentrations during a period of rapid brain growth can
      lead to a permanent deficit in the number of Purkinje cells and granule cells in
      the floccular-parafloccular region of the cerebellum. Sprague-Dawley rat pups
      were artificially reared and were administered alcohol over postnatal days 4
      through 9, a period of brain development similar to that of the human third
      trimester. Two groups received a daily alcohol dose of 4.5 g/kg, administered
      either as a 10.2% solution in two of the 12 daily feedings (10.2% group) or as a
      5.1% solution in four of the 12 feedings (5.1% group). A third group received a
      daily dose of 6.6 g/kg administered as a 2.5% solution in every feeding (2.5%
      group). The condensed patterns of alcohol administration resulted in high peak
      blood alcohol concentrations with near total clearance while the higher daily
      dose (6.6 g/kg), administered continuously, resulted in low but continuous blood
      alcohol concentrations. Pups were allowed to grow to adulthood and killed on
      postnatal day 115. The total number of Purkinje cells and granule cells in the
      floccular-parafloccular region of the cerebellum was estimated using unbiased
      stereological methods. Exposure to alcohol resulted in significant deficits in
      the number of both Purkinje cells and granule cells at 115 days of age in all
      three treatment groups. Most importantly a significant deficit of Purkinje cells
      and granule cells was found following continuous exposure to low blood alcohol
      concentrations, i.e., in the 2.5% group. The total number of Purkinje cells in
      the 2.5% group was 2.33 +/- 0.31 x 10(4) compared with 3.18 +/- 0.30 x 10(4) in
      the artificially reared controls. The total number of granule cells in the 2.5%
      group and the controls was 1.24 +/- 0.10 x 10(7) and 1.64 +/- 0.19 x 10(7),
      respectively. These results support the hypothesis that exposure to a continuous,
      low blood alcohol concentration can result in the death of developing neurons and
      lead to permanent neuronal deficits. The degree of neuronal loss does not
      correlate with the magnitude of the peaks of blood alcohol concentration.

PMID- 8576440
TI  - Morphology of higher-order ocellar interneurons in the cockroach brain.
AB  - Most species of insects have two or three ocelli, in addition to a pair of
      compound eyes. In the cockroach ocellus, a large number of photoreceptors
      converge upon four second-order neurons, which exit the ocellus and project into
      the ocellar tract neuropil of the brain, where they form synapses with at least
      15 third-order neurons. Third-order neurons project into a variety of neuropils
      in the brain, including the posterior slope, a premotor center from which
      descending neurons originate. I examined the morphology and ocellar response of
      neurons in the posterior slope of the cockroach, using intracellular recording
      and stainings. Most ocellar neurons of the posterior slope exhibited transient
      depolarizations at the cessation of ocellar illumination, which seem to reflect
      sign-conserving synaptic input from third-order neurons. Ocellar neurons of the
      posterior slope project into various areas of the brain, including 1) the central
      complex, a higher center implicated in higher locomotory control, 2) the
      pedunculus of the mushroom body, an associative center, 3) the lamina (the first
      neuropil of the culus of the mushroom body, an associative center, 3) the lamina
      (the first neuropil of the optic lobe), 4) the antennal lobe (olfactory center),
      5) the tritocerebrum (mechanosensory center), and 6) the subesophageal and
      thoracic motor centers. These results suggest that the posterior slope is a high
      order ocellar center from which ocellar signals are transmitted to various target
      neuropils of the brain, as well as a premotor center to form descending motor
      commands.

PMID- 8576441
TI  - Immunocytochemical mapping of serotonin and neuropeptides in the accessory
      medulla of the locust, Schistocerca gregaria.
AB  - Accumulating evidence suggests that pigment-dispersing hormone-immunoreactive
      neurons with ramifications in the accessory medulla of the insect brain are
      involved in circadian pacemaking functions. We have used immunocytochemical
      techniques to investigate the neurochemical organization of the accessory medulla
      in the locust Schistocerca gregaria. Local neurons with arborizations largely
      restricted to the accessory medulla are immunoreactive with antisera against
      serotonin, Manduca sexta allatotropin, and Diploptera punctata allatostatin 7.
      Projection neurons with arborizations in the accessory medulla and fibers to the
      lamina and/or several areas in the midbrain including the posterior optic
      tubercles, the inferior and the superior protocerebrum show Phe-Met-Arg-Phe
      (FMRF)amide-, gastrin/cholecystokinin-, crustacean cardioactive peptide-, and
      substance P immunoreactivities. A unique neuron with tangential ramifications in
      the medulla and lamina and varicose terminals in the accessory medulla contains a
      peptide related to locustatachykinin I/II. Double-label experiments show
      colocalization of pigment-dispersing hormone-immunoreactivity with substances
      related to gastrin/cholecystokinin, FMRFamide, substance P, or crustacean
      cardioactive peptide in certain projection neurons of the accessory medulla. The
      results suggest that neuropeptides and biogenic amines play major neuroactive
      roles in the accessory medulla of the locust. The abundance and extensive
      colocalization of neuropeptides in the locust accessory medulla is discussed with
      respect to the possible involvement of this brain area in circadian pacemaking
      functions.

PMID- 8576442
TI  - Thyrotropin-releasing hormone inputs are preferentially directed towards
      respiratory motoneurons in rat nucleus ambiguus.
AB  - In the present study, we assessed the extent of the thyrotropin-releasing hormone
      (TRH) input to motoneurons in the ambigual, facial, and hypoglossal nuclei of the
      rat using a combination of intracellular recording, dye filling, and
      immunohistochemistry. Twelve motoneurons in the rostral nucleus ambiguus were
      labelled by intracellular injection in vivo of Neurobiotin (Vector). Seven out of
      12 ambigual motoneurons displayed rhythmic fluctuations of their membrane
      potential in phase with phrenic nerve discharge, whereas the other five had no
      modulations of any kind. Seven facial motoneurons and seven hypoglossal
      motoneurons were also filled with Neurobiotin. All three motor nuclei contained
      TRH-immunoreactive varicosities, with the largest numbers found in the nucleus
      ambiguus. Close appositions were seen between TRH-immunoreactive boutons and
      every labelled motoneuron. Respiratory-related motoneurons in the nucleus
      ambiguus received the largest number of TRH appositions with 74 +/- 38
      appositions/neuron (mean +/- S.D.; n = 7). In contrast, nonrespiratory ambigual
      motoneurons received significantly fewer TRH appositions (11 +/- 5; n = 5; P <
      0.05; Mann-Whitney U test). Facial motoneurons received about the same number of
      TRH appositions as nonrespiratory ambigual motoneurons, with 13 +/- 4 (n = 7).
      Hypoglossal motoneurons received the fewest appositions from TRH-containing
      boutons, with 8 +/- 2 (n = 7). There were no differences in the TRH inputs to
      respiratory and nonrespiratory motoneurons in the facial and hypoglossal nuclei.
      These results demonstrate that, among motoneurons in the medulla, respiratory
      motoneurons in the rostral nucleus ambiguus are preferentially innervated by the
      TRH-immunoreactive boutons.

PMID- 8576443
TI  - Large retinal ganglion cells in the channel catfish (Ictalurus punctatus): three
      types with distinct dendritic stratification patterns form similar but
      independent mosaics.
AB  - Retinal ganglion cells in the channel catfish (Ictalurus punctatus) were
      retrogradely labelled, and those with the largest somata and thickest primary
      dendrites were categorized by their levels of dendritic stratification. Three
      types were found, each forming a mosaic making up approximately 1% of the
      ganglion cell population. Using a system based on established sublaminar
      terminology, we call these the alpha-a (alpha a), alpha-b (alpha b), and alpha-c
      (alpha c) ganglion cell mosaics. Cells of the alpha a mosaic had large, sparsely
      branched trees in sublamina a at 10-30% of the depth of the inner plexiform layer
      (IPL), sclerad to those of all other large ganglion cells. Some alpha a somata
      were displaced into the IPL or inner nuclear layer (INL) but belonged to the same
      mosaic as their orthotopic counterparts. Cells of the alpha b mosaic had
      dendrites that branched a little more and arborized in sublamina b at 50-60% of
      the IPL depth. Many also sent fine branches into sublamina a, and some were fully
      bistratified in a and b. The alpha c cells arborized in the most vitread
      sublamina, sublamina c, at 80-95% of the IPL depth. The soma areas of the three
      types in the largest retina studied ranged between 139 microns 2 and 670 microns
      2 with significant differences in the order alpha a > alpha c > or = alpha b.
      Analyses based on nearest-neighbour distance (NND) and on spatial auto- and cross
      correlograms showed that each mosaic was statistically regular and independent of
      the others. Mosaic spacings were similar for each type, giving mean NNDs of 242
      279 microns in the largest retina and 153-159 microns in a smaller one.
      Correspondences between these mosaics, previously defined large ganglion cell
      types in catfish, and other mosaic-forming large ganglion cells in fish and frogs
      are discussed along with their implications for neuronal classification,
      function, development, and evolution.

PMID- 8576444
TI  - Three-dimensional distribution of [3H]quinuclidinyl benzilate binding to
      muscarinic cholinergic receptors in the developing human brainstem.
AB  - Acetylcholine has been implicated in brainstem mechanisms of cardiac and
      ventilatory control, arousal, rapid eye movement (REM) sleep, and cranial nerve
      motor activity. Virtually nothing is known about the developmental profiles of
      cholinergic perikarya, fibers, terminals, and/or receptors in the brainstems of
      human fetuses and infants. This study provides baseline information about the
      quantitative distribution of muscarinic cholinergic receptors in fetal and infant
      brainstems. Brainstem sections were analyzed from 6 fetuses (median age: 21.5
      postconceptional weeks), 4 premature infants (median age: 26 postconceptional
      weeks), and 11 infants (median age: 53 postconceptional weeks). One child and
      three adult brainstems were examined as indices of maturity for comparison. The
      postmortem interval in all cases was less than or equal to 24 hours (median: 10
      hours). Muscarinic receptors were localized by autoradiographic methods with the
      radiolabeled antagonist [3H]quinuclidinyl benzilate ([3H]QNB). Computer-based
      methods permitted quantitation of [3H]QNB binding in specific nuclei and three
      dimensional reconstructions of binding patterns. By midgestation, muscarinic
      cholinergic receptor binding is already present and regionally distributed, with
      the highest binding levels in the interpeduncular nucleus, inferior colliculus,
      griseum pontis, nucleus of the solitary tract, motor cranial nerve nuclei, and
      reticular formation. During the last half of gestation, [3H]QNB binding decreases
      in most, but not all of the nuclei sampled. The most substantial decline occurs
      in the reticular formation of the medulla and pons, a change that is not fully
      explained by progressive myelination and lipid quenching. Binding levels remain
      essentially constant in the inferior olive and griseum pontis. Around the time of
      birth or shortly thereafter, the relative distribution of binding becomes similar
      to that in the adult, with the highest levels in the interpeduncular nucleus and
      griseum pontis, although binding levels are higher overall in the infant. In the
      rostral pontine reticular formation, paramedian bands of high muscarinic binding
      are present which do not correspond to a cytoarchitectonically defined nucleus.
      By analogy to animal studies, these bands may comprise a major cholinoreceptive
      region of the human rostral pontine reticular formation involved in REM sleep. In
      the human interpeduncular nucleus in all age periods examined, muscarinic binding
      localizes to the lateral portions bilaterally, indicative of a heterogeneous
      chemoarchitecture. Muscarinic binding is high in the arcuate nucleus, a component
      of the putative respiratory chemosensitive fields along the ventral surface of
      the infant medulla. This observation is consistent with the known effects of
      muscarinic agents on chemosensitivity and ventilatory responses applied to the
      ventral medullary surface in animal models. The nonuniform distribution of
      muscarinic binding in the caudorostral plane in individual brainstem nuclei, as
      illustrated by three-dimensional reconstructions, underscores the need for
      rigorous sampling at precisely matched levels in quantitative studies. This study
      provides basic information toward understanding the neurochemical basis of
      brainstem disorders involving dysfunction of autonomic and ventilatory control,
      arousal, and REM sleep in preterm and full-term newborns and infants and for
      developing cholinergic drugs for such disorders in the pediatric population.

PMID- 8576445
TI  - Distribution of growth-associated class I alpha-tubulin and class II beta-tubulin
      mRNAs in adult rat brain.
AB  - A comprehensive survey of class I alpha-tubulin (alpha 1) and class II beta
      tubulin (beta II) mRNAs was performed using in situ hybridization in order to
      determine the extent of continued expression of these immature tubulin isotype
      mRNAs in the adult rat brain. Qualitatively similar distributions of the two
      isotype mRNAs were observed, with marked variations in hybridization intensity of
      both probes apparent across different brain regions. Neurons in a wide variety of
      structures throughout the brain exhibited intense hybridization signals. While
      the presence of large numbers of neurons with a moderate hybridization intensity
      could account for the relatively high level of total binding in some regions such
      as the cerebellar and dentate granule layers, in most cases higher regional mRNA
      levels reflected greater hybridization intensity per neuron. Little variability
      in hybridization intensity was typically seen between individual cells within
      specific nuclei throughout the brain. The presence of occasional intensely
      labeled neurons scattered throughout the basal ganglia provided the most striking
      exception to this pattern. While no qualitative differences between the
      distributions of alpha 1-tubulin and beta II-tubulin mRNAs were observed,
      consistent differences in the relative intensity of hybridization for alpha 1
      tubulin versus beta II-tubulin mRNA were apparent in a few brain regions.
      Expression by glia did not appear to contribute significantly to detectable
      levels of either alpha 1-tubulin or beta II-tubulin mRNA. These findings suggest
      that continued expression of growth-associated tubulin isotype mRNAs may have
      functional significance in specific neuronal populations of the adult brain.
      Partial overlap between the distributions of alpha 1- and beta II-tubulin mRNAs
      and that of GAP-43 mRNA is discussed, as are potential roles for growth
      associated tubulin gene expression in supporting cytoskeletal turnover, reactive
      axonal growth, and dendritic remodeling in the adult brain.

PMID- 8576446
TI  - Fate of GABAergic septohippocampal neurons after fimbria-fornix transection as
      revealed by in situ hybridization for glutamate decarboxylase mRNA and
      parvalbumin immunocytochemistry.
AB  - Many septohippocampal neurons are GABAergic and are affected by transection of
      the fimbria-fornix, like the septohippocampal cholinergic cells. Here we have
      studied the changes that occur in GABAergic septohippocampal neurons following
      fimbria-fornix transection. For labeling of septohippocampal projection neurons,
      adult Sprague-Dawley rats received injections of the fluorescent tracer Fluoro
      Gold into the hippocampus 1 week prior to bilateral transection of the fimbria
      fornix. After axotomy, rats were allowed to survive for varying periods ranging
      from 3 weeks to 18 months. Following fixation of the animals, sections through
      the septal region were either stained by in situ hybridization for glutamate
      decarboxylase (GAD) mRNA or immunostained for parvalbumin (PARV), which is known
      to be present in GABAergic septohippocampal neurons. In situ hybridization for
      GAD mRNA revealed no statistically significant changes in cell number 3 weeks and
      6 months postlesion. In contrast, PARV-immunoreactive neurons were reduced to 35%
      of control 3 weeks postlesion. This value increased to 66% after 6 months of
      survival. As seen in the electron microscope, axotomized PARV-positive neurons
      exhibited characteristics of vital cells. Most neurons contained lysosomes
      associated with Fluoro-Gold, resulting from retrograde labeling prior to fimbria
      fornix transection. We conclude that mainly PARV-containing GABAergic neurons in
      the medial septal nucleus (MS) project to the hippocampus and are thus heavily
      affected by the lesion but are able to survive and restore the synthesis of PARV.
      The lack of significant changes in the number of GAD mRNA-expressing cells is
      explained by the presence of numerous GABAergic MS neurons not projecting to the
      hippocampus.

PMID- 8576447
TI  - Subsets of midbrain dopaminergic neurons in monkeys are distinguished by
      different levels of mRNA for the dopamine transporter: comparison with the mRNA
      for the D2 receptor, tyrosine hydroxylase and calbindin immunoreactivity.
AB  - The midbrain dopamine system can be divided into two groups of cells based on
      chemical characteristics and connectivity. The dorsal tier neurons, which include
      the dorsal pars compacta and the ventral tegmental area, are calbindin-positive,
      and project to the shell of the nucleus accumbens. The ventral tier neurons are
      calbindin-negative and project to the sensorimotor striatum. This study examined
      the distribution of the mRNAs for the dopamine transporter molecule (DAT) and the
      D2 receptor in the midbrain of monkeys by using in situ hybridization. The
      distribution patterns were compared to that of tyrosine hydroxylase and calbindin
      immunohistochemistry. The results show that high levels of hybridization for DAT
      and the D2 receptor mRNA are found in the ventral tier, calbindin-negative
      neurons and relatively low levels are found in the dorsal, calbindin-positive
      tier. Within the dorsal tier, the dorsal substantia nigra pars compacta has the
      least amount of both messages. These results show that in monkeys, the ventral
      tegmental area and the dorsal pars compacta form a dorsal continuum of dopamine
      neurons which express lower levels of mRNA for DAT and D2 receptor than the
      ventral tier. DAT has been shown to be involved in the selective neurotoxicity of
      N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Different levels of DAT mRNA
      and calbindin may explain the differential effects of MPTP neurotoxicity.

PMID- 8576448
TI  - Interdigitation of nitric oxide synthase-, tyrosine hydroxylase-, and serotonin
      containing neurons in and around the laterodorsal and pedunculopontine tegmental
      nuclei of the guinea pig.
AB  - The topography of neurons containing nitric oxide synthase (NOS) and monoamines
      was investigated in the guinea pig mesopontine tegmentum. NOS-containing neurons
      were identified with NADPH-diaphorase (NADPH-d) histochemistry, and monoamine
      containing neurons were identified with tyrosine hydroxylase (TH) and serotonin
      (5-HT) immunocytochemistry. The distribution of NADPH-d positive cells was
      centered on the laterodorsal tegmental (LDT) and pedunculopontine tegmental (PPT)
      nuclei. Diaphorase-containing cells had a mean soma diameter of 23.0 +/- 4.1
      microns (n = 160) and were distributed inhomogeneously, with numerous cells found
      within densely packed clusters. A nearest-neighbor analysis revealed that these
      cells were closely spaced, with up to 20% within one cell diameter and more than
      50% within two cell diameters of a neighboring NADPH-d cell. Within the LDT and
      PPT, NADPH-d positive cells were mixed with smaller, diaphorase-negative cells
      (diam: 12.8 +/- 3.3 microns; n = 182; P << 0.01). TH-containing cells were not
      organized into a compact LC as in rat and their distribution more closely
      resembled that observed in cat. On average, TH-containing cells (diam: 21.2 +/-
      4.8 microns; n = 160) were smaller than NADPH-d cells (P < 0.01). 5-HT-containing
      cells were mainly located in the raphe nuclei, as in other species. 5-HT
      containing cells (diam: 18.2 +/- 4.4 microns; n = 161) were smaller on average
      than both the NADPH-d (P < 0.01) and TH-containing cells (P < 0.01). An analysis
      of the overlap in soma distributions revealed that TH-containing cells were
      largely interdigitated with NADPH-d containing cells. As much as 78% of the area
      occupied by the NADPH-d cells of LDT was contained within the area occupied by TH
      cells. Substantial numbers of TH and 5-HT immunoreactive processes were seen in
      both LDT and PPT. Varicose 5-HT and TH-containing fibers, as well as thicker,
      possibly dendritic processes containing TH were often seen in close apposition to
      NADPH-d containing somata and proximal dendrites. These results support the
      hypothesis that NADPH-d cells of both the PPT and LDT receive input from TH and 5
      HT cells. Moreover, the clustered substructure of LDT and PPT and the extensive
      overlap of NADPH-d and TH-containing somata raise the possibility that the
      membrane permeable messenger nitric oxide plays a role in modulating TH
      containing somata and their processes as well as 5-HT-containing processes in the
      LDT and PPT.

PMID- 8576449
TI  - Embryonic development of central nervous system myelination in a reptilian
      species, Eumeces fasciatus.
AB  - The myelin proteolipid proteins are a vital component of the vertebrate central
      nervous system (CNS), contributing essential functions to the development of the
      myelinating cells of the CNS and to the structure of CNS myelin. Alternative
      splicing of the proteolipid protein (PLP) gene to produce two related isoforms
      occurs in Mammalia, Aves, and Reptilia, but not Amphibia. As part of a long-term
      investigation into the function of the different isoforms of PLP, embryonic
      development, myelination, and PLP gene expression in reptilian CNS were examined.
      PLP gene expression was already substantial by day 19 (stage 39) of the 27-day
      Eumeces fasciatus egg incubation period. By day 21 of incubation, also stage 39,
      PLP mRNA was at peak levels; there was a significant amount of CNS myelination as
      demonstrated by electron microscopy of the spinal cord; and the reflexive motor
      response was evident. Although most axons were myelinated by the time of
      hatching, myelin sheaths continued to increase in size and compactness after
      hatching. The correlation of physiological development, CNS myelination, and
      expression of the PLP gene in the lizard corresponded well with the developmental
      pattern seen in mammals.

PMID- 8576450
TI  - Fractional reabsorption of calcium, magnesium and phosphate in the kidneys of
      freshwater North American eels (Anguilla rostrata LeSueur) following removal of
      the corpuscles of Stannius.
AB  - Renal function was observed in freshwater North American eels (Anguilla rostrata
      LeSueur) 2 weeks after the removal of the corpuscles of Stannius. There was a
      positive linear correlation between glomerular filtration rates and urine flow
      rates in both sham-operated and stanniectomized eels but there was no difference
      in slope or elevation between the two groups nor did urine flow rates ever exceed
      glomerular filtration rates. Osmolar clearance and free-water clearance were
      unchanged following stanniectomy. Plasma Ca2+ and K+ concentrations increased and
      plasma Mg2+, phosphate, Na+ and Cl- concentrations decreased following
      stanniectomy. Plasma ultrafilterable Ca increased and ultrafilterable Mg
      decreased after stanniectomy but neither changed relative to its total plasma
      concentration. Stanniectomy was followed by a decreased renal tubular
      reabsorption of Mg2+ relative to the amount filtered (CMg/CIn); the same applies
      to CNa/CIn. Even though the filtered load of Ca increased in conjunction with the
      predictable hypercalcemia, there was no change in the fraction of filtered Ca
      reabsorbed. Net tubular secretion of phosphate was observed in both sham-operated
      and stanniectomized eels together with a slight increase in Cphos/CIn following
      stanniectomy. Some or all of these changes in plasma electrolytes and/or the
      modified renal transport of Na+, Mg2+ and possibly phosphate may be caused by the
      changes in cardiovascular function that were recently shown to follow
      stanniectomy.

PMID- 8576451
TI  - Lipoprotein lipase activity and its relationship to high milk fat transfer during
      lactation in grey seals.
AB  - Lipoprotein lipase regulates the hydrolysis of circulating triglyceride and the
      uptake of fatty acids by most tissues, including the mammary gland and adipose
      tissue. Thus, lipoprotein lipase is critical for the uptake and secretion of the
      long-chain fatty acids in milk and for the assimilation of a high-fat milk diet
      by suckling young. In the lactating female, lipoprotein lipase appears to be
      regulated such that levels in adipose tissue are almost completely depressed
      while those in the mammary gland are high. Thus, circulating fatty acids are
      directed to the mammary gland for milk fat production. Phocid seals serve as
      excellent models in the study of lipoprotein lipase and fat transfer during
      lactation because mothers may fast completely while secreting large quantities of
      high fat milks and pups deposit large amounts of fat as blubber. We measured pup
      body composition and milk fat intake by isotope (deuterium oxide) dilution and
      plasma post-heparin lipoprotein lipase activity in six grey seal (Halichoerus
      grypus) mother-pup pairs at birth and again late in the 16-day lactation period.
      Maternal post-heparin lipoprotein lipase activity increased by an average of four
      fold by late lactation (P = 0.027), which paralleled an increase in milk fat
      concentration (from 38 to 56%; P = 0.043). Increasing lipoprotein lipase activity
      was correlated with increasing milk fat output (1.3-2.1 kg fat per day) over
      lactation (P = 0.019). Maternal plasma triglyceride (during fasting) was
      inversely correlated to lipoprotein lipase activity (P = 0.027) and may be
      associated with the direct incorporation of long-chain fatty acids from blubber
      into milk. In pups, post-heparin lipoprotein lipase activity was already high at
      birth and increased as total body fat content (P = 0.028) and the ratio of body
      fat: protein increased (P = 0.036) during lactation. Although pup plasma
      triglyceride increased with increasing daily milk fat intake (P = 0.023), pups
      effectively cleared lipid from the circulation and deposited 70% of milk fat
      consumed throughout lactation. Lipoprotein lipase may play an important role in
      the mechanisms involved with the extraordinary rates of fat transfer in phocid
      seals.

PMID- 8576452
TI  - Mechanisms of fluid and ion secretion by the parotid gland of the kangaroo,
      Macropus rufus, assessed by administration of transport-inhibiting drugs.
AB  - Possible mechanisms of primary fluid formation by macropodine parotid glands were
      investigated in anaesthetized red kangaroos using ion transport inhibitors.
      Carotid plasma amiloride concentrations of 0.05-0.5 mmol.l-1 progressively
      reduced a stable acetylcholine-evoked half-maximal flow rate of 2.0 +/- 0.04 to
      0.22 +/- 0.024 ml.min-1 (mean +/- SEM). Concurrently, saliva bicarbonate
      concentration and secretion fell (135 +/- 1.6 to 67 +/- 1.7 mmol.l-1 and 272 +/-
      7.6 to 15 +/- 2.6 mumol.min-1, respectively); [phosphate], [chloride] and
      [sodium] rose and [potassium] and osmolality were unaltered. High-rate
      cholinergic stimulation did not increase saliva flow beyond 11 +/- 1.0% of that
      for equivalent pre-amiloride stimulation. Equipotent levels of amiloride and
      methazolamide given concurrently were no more effective at blocking flow and
      bicarbonate secretion than when given separately. Furosemide (up to 2 mmol.l-1),
      bumetanide (up to 0.2 mmol.l-1) and ethacrynate (1 mmol.l-1) in carotid plasma
      had no effect on salivary flow or ion concentrations. During methazolamide
      blockade, furosemide did not curtail the concurrent increase in salivary
      [chloride]. Chlorothiazide at 0.25-1.0 mmol.l-1 caused progressive depression of
      saliva flow and [bicarbonate], and elevation of [chloride]. 4-acetamido-4'
      isothiocyanatostilbene-2,2'disulphonic acid at 0.1 mmol.l-1 was without effect,
      whereas at 0.5 mmol.l-1 it stimulated fluid secretion and increased saliva
      [protein], [sodium], [potassium], [bicarbonate] and osmolality. Concurrently,
      mean arterial blood pressure and pulse pressure fell and heart rate, haematocrit
      and carotid artery plasma flow rose. These responses were absent if saliva flow
      was kept constant by reduction in cholinergic stimulation during 4-acetamido-4
      isothiocyanatostilbene-2,2'disulphonic acid administration. It is concluded that
      secretion of primary fluid by the kangaroo parotid is initiated mainly (> 90%) by
      secretion of bicarbonate which is formed in the endpiece cells from CO2 delivered
      by the circulation. No evidence was found for initiation of fluid secretion by
      chloride transport involving basolateral Na(+)-K(+)-2Cl- symports, Na(+)-Cl-
      symports or Cl-/HCO3- antiports.

PMID- 8576453
TI  - The impact of dietary fats, photoperiod, temperature and season on morphological
      variables, torpor patterns, and brown adipose tissue fatty acid composition of
      hamsters, Phodopus sungorus.
AB  - We investigated how dietary fats and oils of different fatty acid composition
      influence the seasonal change of body mass, fur colour, testes size and torpor in
      Djungarian hamsters, Phodopus sungorus, maintained from autumn to winter under
      different photoperiods and temperature regimes. Dietary fatty acids influenced
      the occurrence of spontaneous torpor (food and water ad libitum) in P. sungorus
      maintained at 18 degrees C under natural and artificial short photoperiods.
      Torpor was most pronounced in individuals on a diet containing 10% safflower oil
      (rich in polyunsaturated fatty acids), intermediate in individuals on a diet
      containing 10% olive oil (rich in monounsaturated fatty acids) and least
      pronounced in individuals on a diet containing 10% coconut fat (rich in saturated
      fatty acids). Torpor in P. sungorus on chow containing no added fat or oil was
      intermediate between those on coconut fat and olive oil. Dietary fatty acids had
      little effect on torpor in animals maintained at 23 degrees C. Body mass, fur
      colour and testes size were also little affected by dietary fatty acids. The
      fatty acid composition of brown fat from hamsters maintained at 18 degrees C and
      under natural photoperiod strongly reflected that of the dietary fatty acids. Our
      study suggests that the seasonal change of body mass, fur colour and testes size
      are not significantly affected by dietary fatty acids. However, dietary fats
      influence the occurrence of torpor in individuals maintained at low temperatures
      and that have been photoperiodically primed for the display of torpor.

PMID- 8576454
TI  - Eclosion hormone-stimulated cGMP levels in the central nervous system of Manduca
      sexta: inhibition by lipid metabolism blockers, increase in
      inositol(1,4,5)trisphosphate and further evidence against the involvement of
      nitric oxide.
AB  - Previous studies have shown that the neuropeptide, eclosion hormone, stimulates a
      nitric oxide-independent increase in the levels of cGMP in the nervous system of
      Manduca sexta. By contrast, recent results in Bombyx mori suggest that eclosion
      hormone increases cGMP via the production of nitric oxide. In view of these
      conflicting results we have carried out additional studies to test whether nitric
      oxide is involved in this process in Manduca. Evidence presented here supports
      our earlier observations that in Manduca the eclosion hormone-stimulated increase
      in cGMP is nitric oxide- and carbon monoxide-independent. In addition, we show
      that a wide variety of inhibitors of lipid metabolism block the eclosion hormone
      stimulated cGMP increase. This supports the hypothesis that the activation of the
      guanylate cyclase is mediated by a lipid messenger. We also show that eclosion
      hormone stimulates an increase in the levels of inositol(1,4,5)trisphosphate. The
      time-course of this increase is consistent with the hypothesis that eclosion
      hormone stimulation of a phospholipase C is an early event in the cascade that
      results in an increase in cGMP. Receptor-mediated lipid hydrolysis is often
      mediated by G protein-coupled receptors. Experiments using pertussis toxin show
      that the eclosion hormone-stimulated increase in cGMP is not mediated by a
      pertussis toxin-sensitive G protein.

PMID- 8576455
TI  - Elevating intracellular free Mg2+ preserves sensitivity of Na(+)-K+ pump to ATP
      at reduced temperatures in guinea pig red blood cells.
AB  - Red cells of hibernating species have a higher relative rate of Na(+)-K+ pump
      activity at low temperature than the red cells of a mammal with a typical
      sensitivity to cold. The kinetics of ATP stimulation of the Na(+)-K+ pump were
      determined in guinea pig and ground squirrel red cells at different temperatures
      between 5 and 37 degrees C by measuring ouabain-sensitive K+ influx at different
      levels of ATP. In guinea pig cells, elevation of intracellular free Mg2+ to 2
      mmol.1-1 by use of the divalent cation ionophore A23187 caused the apparent
      affinity of the pump for ATP to increase with cooling to 20 degrees C, rather
      than to decrease, as occurs in cells not loaded with Mg2+. In ground squirrel
      cells raising intracellular free Mg2+ had little effect on apparent affinity of
      the pump for ATP at 20 degrees C. ATP affinity rose slightly with cooling both in
      Mg(2+)-enriched and in control ground squirrel cells. Increased intracellular
      free Mg2+ in guinea pig cells stimulated Na(+)-K+ pump activity so that at 20
      degrees C the pump rate was the same in the Mg(2+)-enriched guinea pig and
      control ground squirrel cells. Pump activity in Mg(2+)-enriched guinea pig cells
      at 5 degrees C was significantly improved but still lower than pump activity in
      control cells from ground squirrel. Thus, loss of affinity of the Na(+)-K+ pump
      for ATP that occurs with cooling in cold-sensitive guinea pig red cells can be,
      at least partially, prevented by elevating cytoplasmic free Mg2+. Conversely, in
      ground squirrel red cells natural rise of free Mg2+ may in part account for the
      preservation of the ATP affinity of their Na(+)-K+ pump with cooling.

PMID- 8576456
TI  - Cholinoceptor-mediated control of catecholamine release from chromaffin cells in
      the American eel, Anguilla rostrata.
AB  - The cholinergic agonist-induced secretion of catecholamines from chromaffin cells
      in the American eel, Anguilla rostrata, was assessed using a saline-perfused
      posterior cardinal vein preparation. Direct membrane depolarization with 60
      mmol.l-1 K+ caused a significant release of catecholamines
      (adrenaline+noradrenaline) into the perfusate which was unaffected by pre
      treatment with the ganglion blocker, hexamethonium (final concentration = 10(-3)
      mol.l-1). The nicotinic receptor agonist, 1,1-dimethyl-4-phenyl-piperazinium
      iodide, evoked catecholamine release in response to several doses exceeding 10(
      7) mol; at 10(-5) mol the response was abolished by pre-treatment with the
      ganglion blocker, hexamethonium (final concentration = 10(-3) mol.l-1). The
      muscarinic receptor agonist, pilocarpine, did not elicit catecholamine release in
      response to any of the doses administered (10(-8)-10(-4) mol). A single injection
      of the mixed nicotinic/muscarinic cholinoceptor agonist, carbachol (10(-5) mol),
      caused the release of catecholamines which was abolished by pre-treatment with
      hexamethonium but which was unaffected by pre-treatment with the muscarinic
      receptor antagonist atropine (final concentration = 10(-5) mol.l-1). The results
      of this study indicate that the process of cholinergic agonist-induced
      catecholamine secretion from the chromaffin cells in the American eel is mediated
      exclusively by activation of nicotinic receptors with no involvement of the
      muscarinic receptor.

PMID- 8576457
TI  - MR-guided fine needle aspiration of breast lesions: initial experience.
AB  - OBJECTIVE: Fine needle aspiration (FNA) is a minimally invasive procedure that is
      used to obtain cytologic specimens of suspicious lesions in the breast. The goal
      of this study was to evaluate the logistics and limitations of MR-guided FNA
      using a prototype breast localization coil. MATERIALS AND METHODS: MR-guided FNAs
      were attempted on 18 lesions (detected on mammography and/or palpation) in 16
      patients. Patients were prone with their breast compressed mediolaterally between
      two plates in a circularly polarized RF coil. Lesion position was determined by
      reference to fiducial markers that corresponded to a grid of holes placed at 5 mm
      intervals in the compression plate. FNA was performed with a 22G non
      ferromagnetic needle. RESULTS: FNA was successful for 11 of 18 lesions (61%). Of
      the seven unsuccessful cases, there were four in which the lesions were too
      posteriorly placed to be accessed through the compression plate by the needle.
      Three cases were too anteriorly placed to be effectively immobilized and,
      although successfully localized, were insufficiently sampled by the FNA
      technique. CONCLUSION: MR-guided FNA is possible using a prototype breast
      localization device in a select group of patients. Current coil design limits its
      use in performing MR-guided FNA on the most anteriorly and posteriorly placed
      breast lesions. Unique requirements of FNA under MR guidance as compared to
      needle localization and biopsy have been identified. Modifications in
      localization hardware and cytology aspiration needles should overcome these
      restrictions.

PMID- 8576459
TI  - MRI of giant cell tumor of the tendon sheath in the cervical spine.
AB  - The authors present a case of giant cell tumor of the tendon sheath (GCTTS) in
      the cervical spine, not previously described in the radiologic literature.
      Diagnostic imaging includes plain film radiographs, bone scintigraphy, CT, and
      MRI. Only one case of tenosynovial giant cell tumor of the cervical spine has
      been reported. The radiological features of this tumor are described along with a
      brief review of GCTTS.

PMID- 8576458
TI  - Cervical and lumbar MRI in asymptomatic older male lifelong athletes: frequency
      of degenerative findings.
AB  - OBJECTIVE: The athletic activity of the adult U.S. population has increased
      markedly in the last 20 years. To evaluate the possible long-term effects of such
      activity on the cervical and lumbar spine, we studied a group of asymptomatic
      currently very active lifelong male athletes over age 40 (41-69 years old, av.
      age 53). MATERIALS AND METHODS: Nineteen active, lifelong male athletes were
      studied with MRI and the results compared with previous imaging studies of other
      populations. An athletic history and a spine history were also taken. RESULTS:
      Evidence of asymptomatic degenerative spine disease was similar to that seen in
      published series of other populations. Degenerative changes including disk
      protrusion and herniation, spondylosis, and spinal stenosis were present and
      increased in incidence with increasing patient age. In this group, all MRI
      findings proved to be asymptomatic and did not limit athletic activity.
      CONCLUSION: The incidence of lumbar degenerative changes in our study population
      of older male athletes was similar to those seen in other populations.

PMID- 8576460
TI  - CT and MRI of aggressive osteoblastoma of thyroid cartilage.
AB  - We present a unique case of aggressive osteoblastoma arising from thyroid
      cartilage. A 52-year-old man presented with a 10 month history of neck discomfort
      but without frank pain. CT and MR examinations disclosed a well defined mass
      arising from the thyroid cartilage. This lesion had areas of coarse
      calcifications and a central area of lucency. The appearance suggested
      chondrosarcoma. Hemilaryngectomy was performed to remove the mass en bloc.
      Surgical pathology diagnosed aggressive osteoblastoma arising from thyroid
      cartilage.

PMID- 8576461
TI  - Malignant myoepithelioma arising in salivary tissue on the masseter muscle: US,
      CT, and MR findings.

PMID- 8576462
TI  - Three-dimensional helical CT of intrahepatic venous structures: comparison of
      three rendering techniques.
AB  - OBJECTIVE: To define the advantages and disadvantages of various rendering
      techniques to obtain three-dimensional (3D) displays of intrahepatic venous
      structures with helical CT data. MATERIALS AND METHODS: After rapid preprocessing
      segmentation of the liver, helical CT data (8 mm slice thickness overlapped every
      4 mm) from 10 patients were reconstructed using maximum intensity projection
      (MIP), volume rendering, and surface rendering algorithms. Three-dimensional
      imaging was evaluated blindly and independently by three observers for presence
      of artifacts and overall quality. RESULTS: Three-dimensional displays showed the
      hepatic veins and fifth order portal branches with the volume and MIP rendering
      techniques. Best overall quality in the 3D representation of the liver was
      achieved with the MIP technique (p < 0.05). Small details in venous anatomy and
      portal involvement by tumor were better imaged with the MIP technique. "Stair
      step" artifacts markedly degraded the 3D displays obtained with the surface
      rendering technique, making it inappropriate for imaging the intrahepatic venous
      structures. CONCLUSION: Maximum intensity projection appears to be an adequate
      technique to perform 3D imaging of intrahepatic venous structures with helical CT
      data when 8 mm slice thicknesses overlapping every 4 mm are used. However,
      optimization of imaging protocols needs to be done and compared in a larger
      series.

PMID- 8576463
TI  - Detection and characterization of hepatocellular carcinoma: value of dynamic CT
      during the arterial dominant phase with uniphasic contrast medium injection.
AB  - OBJECTIVE: Our goal was to assess the effect of dynamic CT during the arterial
      dominant phase with uniphasic injection of intravenous contrast material (5 ml/s)
      in the detection and characterization of hepatocellular carcinomas (HCCs).
      MATERIALS AND METHODS: Three-phase incremental dynamic CT was performed in 66
      patients with 84 HCCs diagnosed by pathologic findings, characteristic
      angiographic findings, and clinical manifestations. One hundred fifty milliliters
      of nonionic contrast medium was administered intravenously by using a power
      injector at a flow rate of 5 ml/s for 30 s, and three-phase images were obtained
      at 20-45 s (arterial dominant phase), 55-80 s (portal venous phase), and 2-4 min
      (equilibrium phase) after the start of uniphasic intravenous injection. Three
      phase images in 66 patients were compared and assessed for the detectability and
      enhancement pattern of the tumors. RESULTS: The arterial dominant phase images of
      dynamic CT showed a moderate to marked hyperattenuation in 73 (87%) of the 84
      HCCs, isoattenuation in 6 (7%), and hypoattenuation in 5 (6%). The portal venous
      phase images showed hyperattenuation in 6 (7%), isoattenuation in 45 (54%), and
      hypoattenuation in 33 (39%). In the equilibrium phase, CT findings showed
      hypoattenuation in 67 (80%) and isoattenuation in 17 (20%). The detectability of
      HCCs in the arterial dominant, portal venous, and equilibrium phase was 93, 46,
      and 80%, respectively. The detectability of HCCs in the arterial dominant phase
      was significantly (p < 0.0001) superior to that in both the portal venous phase
      and the equilibrium phase. CONCLUSION: Dynamic CT during the arterial dominant
      phase with uniphasic injection of intravenous contrast medium (5 ml/s) is a
      useful method in the detection and characterization of HCCs.

PMID- 8576464
TI  - Analysis of models for quantification of arterial and portal blood flow in the
      human liver using PET.
AB  - OBJECTIVE: The purpose of our study was to quantify arterial and portal hepatic
      arterial blood flows. MATERIALS AND METHODS: Four models were developed using
      PET. The first model consisted of the components of the liver and the portal
      system. The second applied "curve analysis" to this model. The third model
      introduced a portosystemic shunt factor, whereas the last model introduced a
      coefficient for circulation time within the portal organs. In 51 patients (34 men
      and 17 women), PET scans of the liver were performed using the H2 15O dynamic
      method. RESULTS: Under all four models, the arterial and portal hepatic arterial
      blood flows of 504 regions of interest were calculated using the nonlinear least
      squares method, and results were compared by the sum of the squares of errors.
      Additionally, results from the H2 15O dynamic method were compared by results
      from the C15O2 steady-state method. CONCLUSION: Of the four models, the last
      model produced curves with the best fit. When hepatic blood flow was quantified
      using PET and the H2 15O dynamic method, a model applying "curve analysis" and
      components related to portosystemic shunting and circulation time was found to be
      most accurate.

PMID- 8576465
TI  - MRI in predicting the response of ovarian endometriomas to hormone therapy.
AB  - OBJECTIVE: Our goal was to investigate the usefulness of MRI in predicting the
      response of endometriomas to hormone therapy. MATERIALS AND METHODS: MRI and
      laparoscopy at the onset of treatment and follow-up MRI after 6 months of hormone
      therapy were performed in 21 patients with 49 endometriomas. T1- and T2-weighted
      images were obtained with a 1.5 T apparatus using a body coil. The lesions were
      divided into a responder group and a nonresponder group according to whether the
      lesion size decreased by > or = 50% or not. RESULTS: With MRI, shading was seen
      in 25 of 27 lesions (93%) from the nonresponder group, but in only 6 of 22 (27%)
      from the responder group. Low SI rim was seen in 59% of the responders and 89% of
      the nonresponders. Multiplicity in 68% of the responders and in 85% of the
      nonresponders and irregularity in 41% of the responders and in 78% of the
      nonresponders were shown. Multiple logistic analysis revealed shading was the
      most important factor in prediction of the response to hormone therapy.
      CONCLUSION: Shading was an important sign in evaluating the response of
      endometriomas to hormone therapy. MRI may assist in selecting the appropriate
      therapy for endometriomas.

PMID- 8576466
TI  - Assessment of bronchiectasis: comparison of HRCT and spiral volumetric CT.
AB  - OBJECTIVE: Our goal was to ascertain the sensitivity of spiral CT for the
      detection of bronchiectasis in comparison with high resolution CT (HRCT).
      MATERIALS AND METHODS: Thirty-one patients with a suspected clinical diagnosis of
      bronchiectasis were evaluated with spiral CT (slice thickness 5 mm, pitch 1,
      reconstruction index 2 mm, 1 s rotation) and HRCT (1.5 mm, interval 10 mm).
      Analysis of the presence, type, and severity of bronchiectasis was performed for
      each bronchopulmonary lobe. RESULTS: In 30 patients, 177 lobes were evaluated. At
      HRCT 14 patients showed signs of bronchiectasis in 32 lobes. Spiral CT confirmed
      the presence in 29 lobes. In one lobe spiral CT was false positive. The severity
      score was the same in 23 lobes, in 4 lobes higher at HRCT, and in 2 lobes higher
      at spiral CT. Spiral CT has a high sensitivity of 91% to detect bronchiectasis
      with a specificity of 99.3%. Spiral CT demonstrates adequately lack of tapering
      of the bronchus. CONCLUSION: In patients with suspected bronchiectasis, HRCT is
      the method of first choice based on greater sensitivity and lower radiation dose.
      However, spiral CT done for other indications is a reliable method for assessment
      of bronchiectasis. Inability of patients to hold their breath did not prove to
      interfere with diagnostic reliability.

PMID- 8576467
TI  - Hepatodiaphragmatic interposition of the colon in the upright and supine
      position.
AB  - OBJECTIVE: Hepatodiaphragmatic interposition of the colon (HDIC) has been
      previously evaluated with chest radiography (CR) of patients examined in an erect
      position. In this work the presence of HDIC was assessed in patients who
      underwent CT in the supine position. MATERIALS AND METHODS: In 1,440 patients,
      806 men and 634 women, 19-83 years old subjected to CR and abdominal CT for
      various indications, HDIC was retrospectively evaluated. RESULTS: In 2.4% of the
      patients HDIC was found using CT in the supine position but in only 0.3% on CR.
      The variation appeared more frequently in men than in women and in older adults
      and individuals with an increased amount of intraabdominal fat. This latter
      finding may represent an additional factor favoring malposition of the colon.
      CONCLUSION: The results of this study indicate that HDIC has a significantly
      greater incidence in the supine position of patients, and it can not be excluded
      on the basis of negative CR.

PMID- 8576468
TI  - Intravascular gas within an ovarian tumor: a CT sign of ovarian torsion.
AB  - A case of twisted ovarian tumor with intravascular gas is presented, and the
      mechanism of the gas formation is discussed. On the basis of the probable
      mechanism of gas formation observed in dead fetuses, the gas seen in the present
      case is considered to have been oxygen released from trapped oxyhemoglobin within
      the tumor vessels. "Intravascular gas" within an ovarian tumor, although
      extremely rare, is diagnostic of ovarian torsion.

PMID- 8576469
TI  - Retrocrural splanchnic nerve alcohol neurolysis with a CT-guided anterior
      transaortic approach.
AB  - Retrocrural splanchnic nerve alcohol neurolysis with a CT-guided anterior
      transortic approach, a new method for splanchnic block alleviation of chronic
      abdominal pain, is described. Ten patients with chronic abdominal pain requiring
      narcotic treatment, six with pancreatic carcinoma, one with gastric carcinoma,
      two with chronic pancreatitis, and one with pain of unknown etiology, were
      referred for splanchnic nerve neurolysis. With CT guidance, a 20 gauge needle was
      placed through the aorta into the retrocrural space at T11-T12, and 5-15 ml 96%
      alcohol was injected into the retrocrural space. Following the procedure, 6 of 10
      patients were pain free, 2 patients had temporary pain relief, and 2 patients
      were without response. There were no significant complications. CT-guided
      anterior transaortic retrocrural splanchnic nerve alcohol neurolysis is
      technically feasible, easier to perform than the classic posterolateral approach,
      and may have less risk of complications. The success rate in this initial trial
      was reasonable and, therefore, this technique provides an additional method for
      the treatment of abdominal pain.

PMID- 8576470
TI  - Transient Ara-C leukoencephalopathy: MR findings.

PMID- 8576471
TI  - MRI of paraganglioma of the filum terminale.

PMID- 8576472
TI  - Cat-scratch disease simulating lymphoma.

PMID- 8576474
TI  - Inferior mesenteric vein thrombosis in Crohn's disease: CT diagnosis.

PMID- 8576473
TI  - MRI of mediastinal parathyroid cystic adenoma causing hyperparathyroidism.

PMID- 8576475
TI  - Aunt Minnie's corner. Tuberous sclerosis.

PMID- 8576476
TI  - Use of spirometry to predict risk of pneumothorax in CT-guided needle biopsy of
      the lung.
AB  - OBJECTIVE: Our goal was to assess the usefulness of spirometry to estimate the
      risk of pneumothorax in patients undergoing percutaneous needle biopsy with CT
      guidance for solitary pulmonary nodule (SPN). MATERIALS AND METHODS: We studied
      the results of 51 consecutive percutaneous needle biopsies with CT guidance for
      SPN obtained between 1988 and 1990. Forty-five men and six women, aged 65 +/- 11
      (36-86) years, were included in the study. All biopsies were performed under CT
      guidance, with 90 mm 25G needles (0.5 mm thickness) fitted into luer-type
      syringes. The number of needle pass attempts never exceeded three. A spirometry
      before biopsy was performed in all patients. RESULTS: Pneumothorax occurred in
      only 10 cases (19%). The patients with pneumothorax showed lower lesion size,
      forced vital capacity (FVC), forced expiratory volume (FEV1), and FEV1/FVC ratio.
      The contribution of these factors to pneumothorax was analyzed by a logistic
      regression model. The FEV1 was most strongly associated with the incidence of
      pneumothorax. We developed an equation for predicting the risk of this
      complication. CONCLUSION: We conclude that decreasing FEV1 is associated with a
      higher pneumothorax rate.

PMID- 8576477
TI  - CT densitometry of the lungs: scanner performance.
AB  - OBJECTIVE: Our goal was to establish the reproducibility and accuracy of the CT
      scanner in densitometry of the lungs. MATERIALS AND METHODS: Scanner stability
      was assessed by analysis of daily quality checks. Studies using a humanoid
      phantom and polyethylene foams for lung were performed to measure reproducibility
      and accuracy. The dependence of the CT-estimated density on reconstruction
      filter, zoom factor, slice thickness, table height, data truncation, and objects
      outside the scan field was determined. RESULTS: Stability of the system at air
      density was within approximately 1 HU and at water density within approximately 2
      HU. Reproducibility and accuracy for densities found for lung were within 2-3%.
      Dependence on the acquisition and reconstruction parameters was neglible, with
      the exceptions of the ultra high resolution reconstruction algorithm in the case
      of emphysema, and objects outside the scan field. CONCLUSION: The performance of
      the CT scanner tested is quite adequate for densitometry of the lungs.

PMID- 8576479
TI  - MR appearance of pulmonary metastatic calcification.
AB  - We report a case of metastatic pulmonary calcification that showed hyperintense
      signal on T1-weighted MRI. This uncommon MR appearance of calcification is
      similar to the MR characteristics of calcification in the brain due to abnormal
      calcium metabolism.

PMID- 8576478
TI  - Calcification of the ligamentum arteriosum in adults: CT features.
AB  - OBJECTIVE: The present study describes the frequency and pattern of ligamentum
      arteriosum calcification seen on chest CT in adults. MATERIALS AND METHODS: We
      retrospectively reviewed 402 sequential unenhanced chest CT studies for
      ligamentum arteriosum calcification, atherosclerotic cardiac or aortic
      calcification, and granulomatous calcification. The pattern of calcification was
      characterized as curvilinear, punctate, or clumped. RESULTS: Mean patient age was
      60 (+/- 18, range 18-97) years with 214 women (53%) and 188 men (47%). Of these
      patients 194 (48%) had calcification in the ligamentum arteriosum including 26
      (6%) with calcification in the ligamentum arteriosum alone, 108 (27%) with
      atherosclerotic calcification, 11 (3%) with granulomatous calcification, and 49
      (12%) with both. A total of 100 patients (25%) had no calcifications. In the
      study population 169 patients (42%) had atherosclerotic calcification, 32 (8%)
      had granulomatous calcification, and 75 (19%) had both. The patterns of
      calcification for the 26 patients with calcification of the ligamentum arteriosum
      alone were curvilinear (7 patients, 27%), punctate (17 patients, 65%), and
      clumped (2 patients, 8%). The pattern of ligamentum arteriosum calcification for
      the 108 patients with only atherosclerotic and ligamentum arteriosum
      calcification was curvilinear (28 patients, 26%), punctate (32 patients, 30%),
      and clumped (48 patients, 44%). The patients without any calcifications and the
      patients with ligamentum arteriosum calcification formed one group (based on
      their similarity in age, mean 47 years) with a prevalence of ligamentum
      arteriosum calcification of 21%. The patients with atherosclerotic and ligamentum
      arteriosum calcification formed a second group (mean age 71 years) with a
      prevalence of ligamentum arteriosum calcification of 65%. CONCLUSION: On
      unenhanced chest CT calcification of the ligamentum arteriosum is a common
      finding in adults and increases in prevalence with increasing age and
      atherosclerosis.

PMID- 8576480
TI  - Calcification as a sign of sarcomatous degeneration of malignant pleural
      mesotheliomas: a new CT finding.
AB  - We present two cases demonstrating, on CT examination, heavily calcified mass
      lesions associated with malignant pleural mesothelioma in workers occupationally
      exposed to asbestos. These masses proved to be osteogenic sarcomatous
      degeneration within mesotheliomas. The observation of dense calcification within
      a pleural mass should raise a suspicion of osteosarcomatous degeneration if it is
      seen in conjunction with other classic signs of malignant pleural mesothelioma.

PMID- 8576481
TI  - Evaluation of thoracic aortic dissection using breath-holding cine MRI.
AB  - OBJECTIVE: Our goal was to determine if breath-hold cine MRI in transaxial planes
      can be used for the evaluation of thoracic aortic dissection instead of
      conventional cine MRI since rapid imaging is required in this clinical setting.
      MATERIALS AND METHODS: Twelve patients with thoracic aortic dissection were
      imaged using a 1.5 T imager. Breath-hold images were acquired with fast cine MR
      sequence (TR/TE = 9/2.8, 20 degrees flip angle) using segmented k-space data
      acquisition. Conventional non-breath-hold cine MR images (TR/TE = 22/7.5, 35
      degrees flip angle, 2 averages) were taken with flow and respiratory
      compensation. RESULTS: Sharpness of edges of the vessels on fast cine MR images
      was better than that on conventional cine MR images in 34 (57%) of 60 images.
      Inhomogeneous blood signal in aortic lumen due to motion artifacts was found in 2
      (3%) of fast cine MR images and in 15 (25%) of conventional cine MR images. The
      contrast-to-noise ratios of fast cine MR images were significantly better than
      those of conventional cine MR images (26.4 +/- 9.1 vs. 18.5 +/- 10.1; p < 0.05)
      when the region of interest for noise was placed to include ghosting artifacts.
      CONCLUSION: Breath-hold cine MRI is a rapid technique that gives high quality
      images of thoracic aortic dissection and can provide a diagnosis in < 10 min of
      imaging time.

PMID- 8576482
TI  - Ultrasmall superparamagnetic iron oxide to enhance MRA of the renal and coronary
      arteries: studies in human patients.
AB  - OBJECTIVE: Our goal was to determine the feasibility of using an intravascular MR
      contrast agent to improve 3D MRA. MATERIALS AND METHODS: Three-dimensional TOF
      MRA was performed in nine patients both prior to and following the administration
      of an ultrasmall particle superparamagnetic iron oxide contrast agent (AMI 227).
      The lengths of both renal arteries were measured from the maximum intensity
      projection (MIP) images as well as the individual partitions. Seven of these
      patients also were studied by a 3D coronary artery MRA sequence. Signal-to-noise
      ratio (SNR) and contrast-to-noise ratio (CNR) measurements of the right coronary
      artery were determined both prior to and following the administration of AMI 227.
      Statistical analysis of both renal artery lengths and right coronary SNR and CNR
      was performed using a one tailed paired t test comparing pre- and postcontrast
      images. RESULTS: The renal artery lengths significantly increased (right and
      artery: 30%, p = 0.001; left renal artery: 25%, p < 0.008) when measured from the
      individual axial slice partitions. No significant increase in length was observed
      on the MIP images following contrast. In the right coronary artery, the SNR
      increased by an average of 80% (p = 0.008) and CNR increased by an average of
      109% (p = 0.007). Increased background signal and superimposed venous structures
      reduced the measurable lengths of the renal arteries from the MIP images.
      CONCLUSION: These studies support the hypothesis that 3D MRA in the body will
      benefit from the use of intravascular contrast agents. Nevertheless, conventional
      MIP processing is unable to reveal the full advantage of the contrast
      improvement.

PMID- 8576483
TI  - Comparison of projection algorithms used for the construction of maximum
      intensity projection images.
AB  - OBJECTIVE: Four methods of producing maximum intensity projection (MIP) images
      were studied and compared. MATERIALS AND METHODS: Three of the projection methods
      differ in the interpolation kernel used for ray tracing. The interpolation
      kernels include nearest neighbor interpolation, linear interpolation, and cubic
      convolution interpolation. The fourth projection method is a voxel projection
      method that is not explicitly a ray-tracing technique. The four algorithms'
      performance was evaluated using a computer-generated model of a vessel and using
      real MR angiography data. The evaluation centered around how well an algorithm
      transferred an object's width to the projection plane. RESULTS: The voxel
      projection algorithm does not suffer from artifacts associated with the nearest
      neighbor algorithm. Also, a speed-up in the calculation of the projection is seen
      with the voxel projection method. Linear interpolation dramatically improves the
      transfer of width information from the 3D MRA data set over both nearest neighbor
      and voxel projection methods. Even though the cubic convolution interpolation
      kernel is theoretically superior to the linear kernel, it did not project widths
      more accurately than linear interpolation. A possible advantage to the nearest
      neighbor interpolation is that the size of small vessels tends to be exaggerated
      in the projection plane, thereby increasing their visibility. CONCLUSION: The
      results confirm that the way in which an MIP image is constructed has a dramatic
      effect on information contained in the projection. The construction method must
      be chosen with the knowledge that the clinical information in the 2D projections
      in general will be different from that contained in the original 3D data volume.

PMID- 8576484
TI  - A comparison of MR and CT in suspected sacroiliitis.
AB  - OBJECTIVE: A prospective study to compare the MR and CT images of patients with
      suspected sacroiliitis and to establish the optimal MR sequences to demonstrate
      the changes of sacroiliitis was conducted. MATERIALS AND METHODS: Thirty-nine
      patients and nine controls were imaged in the axial plane, with SE T1-, T2
      weighted fast spin echo (T2), T1 with fat suppression (T1WFS), and fast short tau
      inversion recovery (fast STIR) sequences on a 1.5 T system. The sacroiliac joints
      of all patients were imaged with CT. The images were evaluated by two independent
      radiologists. Following the blinded reading, direct comparison of T1 and T1WFS,
      T2, and fast STIR of the CT positive group was made to determine the optimal MR
      sequences. RESULTS: The sensitivity and specificity of MR images for the
      detection of cortical erosions and subchondral sclerosis when compared to CT
      images were 100 and 94.3%, respectively; interobserver variation was low (k =
      0.80). T1WFS and fast STIR images were superior to T1 and T2 images,
      respectively, in demonstrating the changes of sacroiliitis. CONCLUSION: MRI
      (T1WFS and fast STIR) can replace CT in cases with a strong clinical suspicion of
      sacroiliitis and equivocal or normal plain radiographs.

PMID- 8576485
TI  - Pulsed magnetization transfer contrast MRI by a sequence with water selective
      excitation.
AB  - OBJECTIVE: A water selective SE imaging sequence was developed providing suitable
      properties for the assessment of magnetization transfer (MT) effects in tissues
      with considerable amounts of fat. MATERIALS AND METHODS: The sequence with water
      selective excitation and slice selective refocusing combines the following
      features: The RF exposure on the macromolecular protons is relatively low for
      single slice imaging without MT prepulses, since no additional pulses for fat
      saturation are necessary. Water selection by frequency selective excitation
      diminishes faults in the subtraction of images recorded with and without MT
      prepulses (which might arise from movements). RESULTS: High differences in the
      signal amplitudes from hyaline cartilage and muscle tissue were obtained
      comparing images recorded with irradiation of the series of prepulses for MT and
      those lacking MT prepulses. Utilizations of the described water selective
      approach for the assessment of MT effects in lesions of cartilage and bone are
      demonstrated. MT saturation was also examined in muscles with fatty degeneration
      of patients suffering from progressive muscular dystrophy. CONCLUSION: The
      described technique allows determination of MT effects with good precision in a
      single slice, especially in regions with dominating fat signals.

PMID- 8576486
TI  - Intraligamentous ganglion cysts of the anterior cruciate ligament: MR findings
      with clinical and arthroscopic correlations.
AB  - OBJECTIVE: Magnetic resonance findings with clinical and arthroscopic correlation
      of intraligamentous cysts of the anterior cruciate ligament (ACL) are presented.
      MATERIALS AND METHODS: Three cases of intraligamentous cysts of the ACL were
      identified out of 681 knee MRI examinations over a 2-year period. Arthroscopy and
      postoperative MRI were performed in all three patients, each of whom experienced
      knee pain with extreme flexion and extension. RESULTS: In all three cases the
      intraligamentous cyst was homogeneously hypointense on T1-weighted imaging and
      hyperintense on T2-weighted imaging relative to the ACL. Two of the three ACL
      cysts required a 70 degrees scope for adequate visualization and establishment of
      posteromedial and posterolateral portals for arthroscopic treatment. One cyst
      could not be visualized arthroscopically and probing of the ACL from the anterior
      portal resulted in drainage of the cyst. No patient had presence of ACL cyst on
      follow-up MRI or recurrence of symptoms at a mean of 24 months. CONCLUSION:
      Intraligamentous cyst of ACL is a rare cause of knee pain. It should be suspected
      in patients having chronic pain with extremes of motion. Magnetic resonance
      findings are diagnostic and help to guide arthroscopy.

PMID- 8576487
TI  - In vivo MRI characteristics of lipoma arborescens utilizing fat suppression and
      contrast administration.
AB  - Lipoma arborescens or villous lipomatous proliferation of the synovium is a rare
      lesion. We describe the in vivo imaging characteristics of lipoma arborescens of
      the knee utilizing fat suppression techniques and contrast medium administration.
      As expected, the lesion demonstrated signal loss when utilizing fat suppression.
      In addition, no contrast enhancement was noted. When a synovial process
      demonstrates isointensity with subcutaneous fat on all pulse sequences and no
      contrast enhancement, lipoma arborescens should be the primary diagnosis
      consideration.

PMID- 8576488
TI  - A computerized approach for morphological analysis of the corpus callosum.
AB  - OBJECTIVE: A new technique for analyzing the morphology of the corpus callosum is
      presented, and it is applied to a group of elderly subjects. MATERIALS AND
      METHODS: The proposed approach normalizes subject data into the Talairach space
      using an elastic deformation transformation. The properties of this
      transformation are used as a quantitative description of the callosal shape with
      respect to the Talairach atlas, which is treated as a standard. In particular, a
      deformation function measures the enlargement/shrinkage associated with this
      elastic deformation. Intersubject comparisons are made by comparing deformation
      functions. RESULTS: This technique was applied to eight male and eight female
      subjects. Based on the average deformation functions of each group, the posterior
      region of the female corpus callosum was found to be larger than its
      corresponding region in the males. The average callosal shape of each group was
      also found, demonstrating visually the callosal shape differences between the two
      groups in this sample. CONCLUSION: The proposed methodology utilizes the full
      resolution of the data, rather than relying on global descriptions such as area
      measurements. The application of this methodology to an elderly group indicated
      sex-related differences in the callosal shape and size.

PMID- 8576489
TI  - Clustered breast microcalcifications: evaluation by dynamic contrast-enhanced
      subtraction MRI.
AB  - OBJECTIVE: Our goal was to evaluate dynamic contrast-enhanced subtraction MRI in
      the diagnosis of isolated clustered calcifications of the breast. MATERIALS AND
      METHODS: One hundred seventy-two patients underwent surgical biopsy for isolated
      clustered breast calcifications. Their mammograms showed round (n = 88) or
      linear/irregular (n = 84) microcalcifications. All patients had a preoperative Gd
      DOTA-enhanced subtraction dynamic study. Any early contrast enhancement in the
      breast parenchyma concomitant with early enhancement of normal vessels was
      considered positive. RESULTS: Fifty-eight in situ carcinomas, 22 invasive
      carcinomas, and 92 benign lesions were found at histological analysis. Dynamic MR
      sequences showed early contrast enhancement in 76 of 80 malignant lesions
      (sensitivity 95%) and in 45 of 92 benign lesions (specificity 51%). Two invasive
      and two intraductal carcinomas did not show early contrast enhancement. Three
      independent observers agreed in rating early contrast enhancement in 143 of 172
      lesions. CONCLUSION: Poor specificity limits the diagnostic accuracy of dynamic
      contrast-enhanced subtraction MRI in distinguishing benign from malignant
      microcalcifications on mammography.

PMID- 8576490
TI  - Automatic atlas-based volume estimation of human brain regions from MR images.
AB  - OBJECTIVE: MRI offers many opportunities for noninvasive in vivo measurement of
      structure-function relationships in the human brain. Although automated methods
      are now available for whole-brain measurements, an efficient and valid automatic
      method for volume estimation of subregions such as the frontal or temporal lobes
      is still needed. MATERIALS AND METHODS: We adapted the Talairach atlas to the
      study of brain subregions. We supplemented the atlas with additional boxes to
      include the cerebellum. We assigned all the boxes to 1 of 12 regions of interest
      (ROIs) (frontal, parietal, temporal, and occipital lobes, cerebellum, and
      subcortical regions on right and left sides of the brain). Using T1-weighted MR
      scans collected with an SPGR sequence (slice thickness = 1.5 mm), we manually
      traced these ROIs and produced volume estimates. We then transformed the scans
      into Talairach space and compared the volumes produced by the two methods
      ("traced" versus "automatic"). The traced measurements were considered to be the
      "gold standard" against which the automatic measurements were compared. RESULTS:
      The automatic method was found to produce measurements that were nearly identical
      to the traced method. We compared absolute measurements of volume produced by the
      two methods, as well as the sensitivity and specificity of the automatic method.
      We also compared the measurements of cerebral blood flow obtained through
      [15O]H2O PET studies in a sample of nine subjects. Absolute measurements of
      volume produced by the two methods were very similar, and the sensitivity and
      specificity of the automatic method were found to be high for all regions. The
      flow values were also found to be very similar by both methods. CONCLUSION: The
      automatic atlas-based method for measuring the volume of brain subregions
      produces results that are similar to manual techniques. The method is rapid,
      efficient, unbiased, and not subject to the problems of rater drift or
      potentially poor interrater reliability that plague manual methods. Consequently,
      this method may be very useful for the study of structure-function relationships
      in the human brain.

PMID- 8576491
TI  - Individualized enhancement programs for nurses that promote competency.
AB  - Working in a cost-conscious health care environment changes the accessibility to
      conferences, workshops and other continuing education offerings. Educators,
      employers and individual nurses are compelled to be innovative in their approach
      to maintaining competency through continuing education (CE). Greater emphasis
      must be placed on effectively matching CE programs with carefully targeted
      learning needs. This article illustrates a four-phase approach to an
      individualized enhancement program that incorporates job expectations and
      competencies. The phases are: 1) completing a needs assessment, 2) defining
      learning objectives, 3) assessing available learning resources, and 4) evaluating
      the CE experience.

PMID- 8576492
TI  - Concept maps: linking nursing theory to clinical nursing practice.
AB  - The purpose of this article is to offer a different methodology for teaching and
      learning in continuing nursing education and staff development. This article
      describes a qualitative research study that analyzed how linkages are made
      between theoretical material and clinical nursing practice. Findings indicate
      that nursing students did not link the elements of nursing process together, that
      clinical preparation was not linked to theoretical material, that the meaning
      students made of the information was different than the instructors' and that
      concepts from the basic sciences were not incorporated into student meaning
      structures. Implications for the use of concept maps as an educational strategy
      in continuing nursing education are drawn.

PMID- 8576493
TI  - From RN to BSN: seeing familiar situations in different ways.
AB  - Registered nurses enrolled in post-RN programs are a special group of students
      with unique learning needs. One important outcome of a successful post-RN program
      is the ability of its graduates to see familiar situations in different ways and
      to demonstrate these changes in new and different approaches to patient care.
      This shift in the way nurses see themselves and their worlds can be described and
      explained by Mezirow's Theory of Perspective Transformation. This article
      discusses perspective transformation related to post-RN students in nursing
      programs; describes teaching-learning models that assists perspective
      transformation to take place; identifies conditions that promote perspective
      transformation; and suggests some strategies to facilitate the process.

PMID- 8576494
TI  - State and association/certifying boards CE requirements.

PMID- 8576495
TI  - Qualitative needs assessment prior to a continuing education program.
AB  - The usefulness of qualitative research is illustrated by the presentation of a
      needs assessment among Dutch surgical cancer nurses and patients. Participant
      observations and qualitative interviews showed that nurses usually did not assess
      pain systematically, gave insufficient pain medication, were unaware of the
      effectiveness of some nonpharmacological techniques, and often felt powerless in
      giving psychosocial support. Patients appeared inhibited in expressing pain and
      inhibition was reinforced by ineffective interactions with nurses. using these
      findings, a continuing education program on pain assessment and management was
      developed.

PMID- 8576496
TI  - Ethical decision-making in nursing: implications for continuing education.
AB  - Staff nurses make ethical decisions daily. It is important that nurses know how
      to manage those decisions appropriately so that clients' ethical rights are
      honored without compromising the nurse's own moral conscience. In this
      phenomenological study, 19 staff nurses described their experiences in making
      ethical decisions in their practices. The interviews were transcribed and
      analyzed using Giorgi's phenomenological steps. The description of the nurses'
      experiences identified two distinct components of the ethical decision-making
      process: deliberation and integration. The findings suggest that nurses need to:
      a) recognize the ethical nature of their work, b) discern which ethical decisions
      are theirs to make, and c) acknowledge their authority to make ethical decisions
      in their practices. These findings have important implications for the continuing
      education of nurses regarding ethical decision-making.

PMID- 8576497
TI  - Assessment of new nurse educators.
AB  - New nursing educators are typically hired from a pool of clinical experts due to
      a limited number of nurse educators prepared in adult education at the master's
      level. To enable identification of new nurse educator learning needs and
      individualization of development, a performance-based approach to orientation was
      designed. Relevant assessment tools were developed using three steps. First, the
      performance expectations of the role in an acute care facility were articulated.
      Second, the nine performance expectations were categorized into three skill
      areas: critical thinking, interpersonal relationships (IPR), and technical (del
      Bueno, Weeks, & Brown-Stewart, 1987). Lastly, assessment tools were designed to
      elicit performances in each of the three areas. Plans are underway for validity
      testing.

PMID- 8576498
TI  - Does walking decrease the risk of cardiovascular disease hospitalizations and
      death in older adults?
AB  - OBJECTIVES: The purpose of this study was to determine whether walking is
      associated with a reduced risk of cardiovascular disease hospitalization and
      death in community-dwelling older men and women. DESIGN: A prospective study,
      with follow-up time of 4 to 5 years (average 4.2 years). SETTING: A western
      Washington health maintenance organization. PARTICIPANTS: Men and women aged 65
      years and older from a random sample of HMO enrollees invited by mail to
      participate in a health promotion intervention trial (36% accepted the invitation
      and completed questionnaires). This report is based on 1645 older adults without
      severe disability and without history of heart disease. Vital status
      ascertainment was complete (100%), and only 2.6% did not complete the follow-up.
      MEASUREMENTS: Reported frequency and duration of walking for exercise, work,
      errands, pleasure, and hiking in the 2 weeks before baseline were used to
      classify hours of walking per week. The two main outcomes were: (1)
      cardiovascular disease hospitalizations with a discharge diagnosis of coronary
      (ICD-9-CM 410-414) or other cardiovascular diseases (ICD-9-CM 390-409, 415-448)
      documented by computerized hospitalization records and (2) death. Numerous
      potential confounding factors were considered, including age, sex, treated high
      blood pressure, current estrogen use and chronic disease score (ascertained by
      computerized medical and pharmacy records), and ethnicity, education, income,
      physical function, self-rated health status, smoking, alcohol intake, and body
      mass index (ascertained by self-report on the mailed questionnaire). RESULTS:
      Walking more than 4 hours/week was associated significantly with a reduced risk
      of cardiovascular disease hospitalization in both sexes combined compared with
      walking less than 1 hour/week (age and sex-adjusted relative risk = 0.69; 95%
      confidence interval, 0.52-0.90). This association was not altered by adjustment
      for baseline cardiovascular risk factors and indicators of general health status.
      The association was present in all age groups, among those with and without
      physical limitations, and also among those who did and did not also participate
      in more vigorous physical activities. Walking more than 4 hours/week was also
      associated with a reduced risk of death (age and sex-adjusted relative risk =
      0.73; 95% confidence interval, 0.48-1.10), however, this association was
      substantially diminished by adjustment for cardiovascular risk factors and
      measures of general health status. CONCLUSIONS: Walking more than 4 hours/week
      may reduce the risk of hospitalization for cardiovascular disease events. The
      association of walking more than 4 hours/week with reduced risk of death may be
      mediated by effects of walking on other risk factors. These findings provide much
      stronger evidence than previously available for advising older men and women to
      embark on or maintain a sustained program of walking to prevent cardiovascular
      disease events.

PMID- 8576499
TI  - Circulatory responses to weight lifting, walking, and stair climbing in older
      males.
AB  - OBJECTIVES: To compare the heart rate and intra-arterial blood pressure responses
      during weight lifting, horizontal and uphill walking, and stair climbing in older
      male subjects. DESIGN: We used intra-brachial artery catheterization to compare
      the arterial blood pressure (ABP) and heart rate (HR) responses during 10
      repetitions (approximately 40 s) of single-arm curl (SAC) and single-arm overhead
      military press (SAMP) (70% of the one repetition maximum-1RM); 12 repetitions
      (approximately 50 s) of single- (SLP) and double-leg press (DLP) weight-lifting
      exercises (80% of 1RM); 10 minutes of horizontal treadmill walking (T10) at 2.5
      mph holding a 20-pound weight in minutes 4 to 6 (T10) and 30 pounds in minutes 8
      to 10 (T10); 4 minutes of treadmill walking (T4) at 3.0 mph up an 8% incline; and
      12 flights (192 steps) of stair climbing (STR) at 60 to 65 steps/minute on a
      Stiarmaster 6000 ergometer (approximately 3 minutes). SETTING: McMaster
      University, Hamilton, Ontario, Canada. PARTICIPANTS: Seventeen healthy males aged
      (mean +/- SE) 64.4 +/- 0.6 years. MEASUREMENTS: Continuous intra-arterial
      measurements of systolic, diastolic, and mean arterial pressure and heart rate
      and rate-pressure product. RESULTS: The peak values of HR, ABP and rate-pressure
      product (HR.BPs/1000;(RPP,10(3))) were not systematically ordered among the
      various activities. The lowest peak values for all variables were recorded during
      the initial 4 minutes of horizontal treadmill walking. The STR and T4 walking
      exercises elicited higher HRs (151 +/- 3.2 and 121 +/- 3.4 bpm) than the weight
      lifting (range from 100 +/- 4.8 (SAC) to 113 +/- 3.8 bpm (SAMP)), but the
      converse was true for diastolic pressure (range from 128 +/- 6.3 (SAC) to 151 +/-
      4.8 mm Hg (SAMP) versus 101 +/- 2.5 (T4) to 118 +/- 3.4 mm Hg (T10) and mean
      arterial pressure (range from 145 +/- 4.5 (SAC) to 158 +/- 4.8 mm Hg (SAMP)
      versus 129 +/- 3.4 in T4 to 148 +/- 3.8 (T10) and 157 +/- 4.1 mm Hg (STR)). The
      peak systolic pressure was greatest in STR (271 +/- 9.6 mm Hg) followed by SAMP
      (261 +/- 9.3 mmHg) and T10 (244 +/- 6.4 mm Hg) and was lowest in SAC (224 +/-
      10.5 mm Hg) and T10 (220 +/- 5.7 mm Hg). The peak RPP descended in sequence from
      STR (41 +/- 1.8), SAMP (29.8 +/- 1.7), T4 (28.1 +/- 1.3), DLP (27.2 +/- 1.3), T10
      (27.1 +/- 1.4), SLP (25.4 +/- 1.7), T10 (22.7 +/- 1.2) and SAC (22.0 +/- 2.2).
      CONCLUSION: We concluded that older adults who engage in weight lifting with
      heavy submaximal loads are exposed to no more peak circulatory stress than that
      created during a few minutes of inclined walking. Moreover, climbing only three
      to four flights of stairs at a moderate pace (approximately 50-70 s) elicits peak
      circulatory demands similar to, but at a much more rapid rate of adjustment than,
      10 minutes of horizontal walking at 2.5 mph intermittently carrying a 30-pound
      weight or 4 minutes of walking up a moderately steep slope.

PMID- 8576500
TI  - Predictors of change in walking velocity in older adults.
AB  - OBJECTIVE: To determine factors that predict change in walking velocity in older
      people using a multivariate model. DESIGN: Longitudinal observational study.
      SUBJECTS: A total of 588 persons older than age 60, including subjects residing
      in a continuing care retirement community (CCRC) (n = 248), and homebound (n =
      79) and ambulatory (n = 261) subjects. Mean age at baseline = 77. MEASUREMENT:
      Independent variables included demographics, physician measures of lower
      extremity joint impairment and other musculoskeletal and neurological variables,
      comorbidities derived from physical examination and chart abstract, self-assessed
      arthritis pain, depression, and anxiety. The major dependent variables were 2-
      and 4-year decline in walking velocity below a threshold associated with nursing
      home placement. MAIN RESULTS: From baseline to Year 4, median walking velocity
      declined from 61.8 to 53.0 m/min, and the proportion of subjects above a
      threshold value of 11.5 m/min declined from 95.3% to 80.4%. Age, joint
      impairment, and weakness of quadriceps, measured at baseline, predicted 2-year
      and 4-year decline in walking velocity. CONCLUSIONS: The findings indicate that
      joint impairment and quadriceps strength contribute significantly to crossing a
      clinically significant threshold in walking velocity among older people over
      time. Future research is needed to determine whether these risk factors can be
      modified through preventive interventions such as muscle-strengthening exercises
      and pain medication.

PMID- 8576501
TI  - 1H-MRS, MRI-based hippocampal volumetry, and 99mTc-HMPAO-SPECT in normal aging,
      age-associated memory impairment, and probable Alzheimer's disease.
AB  - OBJECTIVE: To better understand how to differentiate the "in vivo" normal aging
      brain from pathological conditions, namely dementia of the Alzheimer type (DAT),
      by means of magnetic resonance imaging (MRI), single photon emission computerized
      tomography (SPECT), and proton magnetic resonance spectroscopy (1H-MRS), to show
      neuroanatomical, perfusional and neurochemical details, respectively. DESIGN: 1H
      MRS, MRI-based hippocampal volumetry and 99mTc-HMPAO SPECT were performed in
      healthy older subjects as well as patients suffering from age-associated memory
      impairment (AAMI) and dementia of Alzheimer type (DAT). SUBJECTS AND SETTING:
      Eighteen subjects were selected from those referred to an outpatient clinic for
      diagnostic evaluation of cognitive impairment entered the study. Six patients
      fulfilled NINCDS-ADRDA diagnostic criteria for DAT, six subjects were affected by
      AAMI, and six cognitively healthy subjects, selected from among relatives of the
      patients, were defined as controls. METHODS: The 1H-MRS and MRI studies were
      performed on a 1.5 Tesla NMR-imaging system equipped with a spectroscopy research
      package. SPECT scans were performed on a Gamma 11 computer system. FINDINGS: 1H
      MRS showed significantly lower N-acetylasparatate concentration in DAT and AAMI
      compared with controls. Conversely, mean inositol concentration was significantly
      higher in DAT than in controls, whereas AAMI subjects registered intermediate
      values. MRI measurements showed significantly reduced volumes of hippocampal
      formations in DAT and AAMI groups compared with controls. Finally, 99mTc-HMPAO
      SPECT showed a significant frontal, temporo-parietal, and occipital hypoperfusion
      in DAT patients only. CONCLUSIONS: These findings support the hypothesis of a
      continuum among the three conditions studied, or at least between AAMI and DAT,
      where AAMI seems to be an early, monosymptomatic stage of Alzheimer disease.
      Accepting this view, it would be questionable to maintain the term "age
      associated memory impairment" as a discrete entity.

PMID- 8576502
TI  - Nocturnal enuresis in community-dwelling older adults.
AB  - OBJECTIVE: To investigate the prevalence and characteristics of nocturnal
      enuresis in community-dwelling older adults and to identify potential
      predisposing variables. DESIGN: Interview survey. SETTING: Five rural counties in
      northwestern Pennsylvania. PARTICIPANTS: Subjects were 3884 community-dwelling
      older adults aged 65 to 79 years who volunteered for a health promotion
      demonstration. MEASUREMENTS: The dependent variable was self-reported accidental
      loss of urine during sleep. Independent variables included demographic variables,
      self-reported disease history and symptomatology, and standardized screening
      instruments for depression (CES-D), dementia (MMSE), and functional status
      (ADLs). MAIN RESULTS: Prevalence of nocturnal enuresis was 2.1%, and was
      significantly higher among women (2.9%) compared with men (1.0%; P < .0001).
      Compared with subjects with daytime incontinence only, those with nocturnal
      enuresis reported greater severity and impact of incontinence on several
      parameters. Enuretics were more likely to have received treatment; treatment
      outcome, however, was significantly less successful. In univariate analyses,
      enuresis was significantly associated with symptoms of congestive heart failure
      (CHF), impairment in activities of daily living, depression, and use of sleep
      medications at least once per week. In stepwise logistic regression modeling, two
      symptoms of congestive heart failure and regular use of sleep medication entered
      the model. CONCLUSIONS: Nocturnal enuresis appears to be uncommon among older
      adults, but it may be associated with poorer therapeutic outcomes compared with
      the more common forms of daytime incontinence. The findings are consistent with
      the hypothesis that daytime fluid accumulation followed at night by mobilization
      of excess fluid is a contributor to enuresis in older adults.

PMID- 8576503
TI  - Life-sustaining treatment decisions by spouses of patients with Alzheimer's
      disease.
AB  - OBJECTIVE: To examine the anticipated decisions to consent to or to forgo life
      sustaining treatment by spouses of patients with Alzheimer's disease and to
      describe the relationship of spouse and patient characteristics to predicted
      decisions. DESIGN: Prospective quantitative study. SETTING: The Aging and
      Dementia Research Center (ADRC), part of an Alzheimer's Disease Center Core
      Grant, at New York University Medical Center. PARTICIPANTS: Fifty spouse
      caregivers of Alzheimer's disease patients, evaluated at the ADRC, who had a
      minimum Stage 4 on the Global Deterioration Scale. MEASUREMENTS: Spouses were
      presented with two conditions (critical illness and irreversible coma) and rated
      their agreement with, certainty of, and comfort with four treatments
      (resuscitation, breathing machine, feeding tube, and antibiotics). Data were also
      obtained as to patients' current quality of life, spouses' standard of decision
      making, and spouse burden. RESULTS: Eighteen of 50 patients had a durable power
      of attorney for health care, 20 of 50 had a living will, and 26 of 50 had
      neither. In the face of critical illness, almost equal numbers of spouses would
      consent to or forgo CPR, 28 of 50 would forgo a breathing machine, 21 of 50 a
      would forgo a feeding tube, and 5 of 50 would forgo antibiotics. Five of 50 would
      forgo all four treatments, and 12 of 50 all but antibiotics. Spouses were
      significantly more likely to forgo treatment in the face of coma than for
      critical illness (P < .001). Spouses were more certain about decisions related to
      coma than to critical illness (P < .001), and there was a positive and
      significant correlation between certainty and comfort (P = .001). Those
      consenting to treatment were more comfortable than those forgoing treatment (for
      CPR and antibiotics P = .001). Spouses of patients with Stage 7 AD were more
      likely to forgo CPR than those with Stages 4 to 6 AD (P < .001). Only two of 50
      spouses selected descriptors congruent with a purely substituted judgment
      standard of decision-making. An equal number of spouses rated patient quality of
      life as good, fair, or poor. For critical illness, the poorer the quality of life
      rating, the more likely the spouses were to forgo feeding tubes (P < .001). There
      was a trend for highly burdened spouses to consent to treatment. CONCLUSIONS: The
      results provide evidence that spouses of patients with AD anticipate forgoing
      life-sustaining treatments in the face of coma but are less sure about choices
      for critical illness. Although preliminary in nature, findings suggest that
      doctors, nurses, and social workers need to provide additional support to spouses
      choosing to forgo rather than consent to treatment and need to inquire as to what
      spouses perceive as the factors that are important to them in making a decision.

PMID- 8576504
TI  - Prevalence of dementia and distribution of ApoE alleles in Japanese centenarians:
      an almost-complete survey in Yamanashi Prefecture, Japan.
AB  - OBJECTIVE: To determine the prevalence and types of dementia in centenarians and
      to examine whether the ApoE epsilon 4 allele has significant impact on the
      development of Alzheimer's disease (AD) in the population. DESIGN: Cross
      sectional study and a 6-month prospective study. SETTING: Yamanashi Prefecture,
      Japan. PARTICIPANTS: Forty-seven centenarians participated in the study to
      determine the prevalence and types of dementia. Thirty-three of the 47
      participated in the study of ApoE genotyping. As controls, 224 demented older
      adults participated in the genetic study. Their age at onset was < 90 years.
      OUTCOMES: Prevalence of dementia based on DSM-III-R; types of dementia based on
      NINCDS-ADRDA and ICD-10; distribution on ApoE alleles in the centenarians and in
      the controls; and the 6-month mortality rate of the subjects. MAIN RESULTS: Of 47
      centenarians, 70.2% had dementia, and AD accounted for the majority (75.8%) of
      the dementia cases. The distribution of ApoE alleles in all the subjects and the
      AD subjects was epsilon 2: 4.6% vs. 0%; epsilon 3: 90.1% vs. 94.1%; epsilon 4:
      4.6% vs. 5.9%. The frequency of the epsilon 4 allele in the AD patients showed a
      tendency to decrease with increasing age, ranging from 38% for those with an age
      at onset of < 60 years to 22% for those with an age at onset of ranging from 80
      to 89 years. The 6-month mortality rate was 27% (9/33) for the demented
      centenarians, whereas none of the 14 nondemented centenarians died. CONCLUSION:
      This almost-complete survey, conducted in a prefecture of Japan, revealed a high
      prevalence of dementia in centenarians. The ApoE epsilon 4 allele does not have
      an impact on the development of AD in centenarians.

PMID- 8576505
TI  - Falls leading to femoral neck fractures in lucid older people.
AB  - OBJECTIVE: To analyze the mechanisms of falls that result in femoral neck
      fractures among lucid older people. DESIGN: A cross-sectional study. SETTING: An
      orthopedic university hospital department. PARTICIPANTS: A consecutive series of
      123 lucid patients, 65 years of age or more, who were admitted for femoral neck
      fractures. MEASUREMENTS: On admission, the subjects were interviewed about
      fracture accident characteristics, and falling mechanisms were classified. An
      arterial blood gas sample was taken from each patient soon after admission. Based
      on data regarding drug consumption and social and medical characteristics, a fall
      risk index was calculated for each subject. RESULTS: It was ascertained that 95%
      of the fractures were caused by falls and < 2% were spontaneous. Most accidents
      (68%) took place indoors, 47% of the falls were classified as extrinsic, 24% as
      intrinsic, 7% as nonbipedal, and 22% remained unclassified. Almost all outdoor
      falls were extrinsic; however, intrinsic falls were as common as extrinsic falls
      indoors (P < .001). Extrinsic fallers presented a significantly lower fall-risk
      index score than subjects with fractures caused by intrinsic, nonbipedal, and
      unclassifiable falls. A large proportion of subjects (24%) wre hypoxemic (pO2 < 8
      kPa) on admission, and patients who sustained fractures at night had lower oxygen
      tension than that of daytime fallers (P = .006). CONCLUSIONS: Accidental falls
      are the primary cause of femoral neck fractures. Preventive actions should be
      directed toward intrinsic, as well as extrinsic, risk factors for falls.
      Hypoxemia might be a risk factor for falls, especially those falls that occur at
      night.

PMID- 8576506
TI  - Evaluation of a self-medication program.
AB  - OBJECTIVE: To determine the effect of an inpatient self-medication program (SMP)
      on the ability to self-medicate, patient medication knowledge, compliance, and
      patient morale. DESIGN: Randomized controlled clinical trial. POPULATION: One
      hundred seven consecutive patients admitted to a geriatric assessment and
      rehabilitation program were randomized to either participate in the SMP or to
      receive standard care. INTERVENTION: The SMP was a three-stage program in which
      patients were given increasing responsibility for the administration of their own
      medications. MEASUREMENTS: Ability to self-medicate on discharge from hospital;
      medication compliance at 1 month; patient medication knowledge; Philadelphia
      Morale Scale. MAIN RESULTS: Participation in the self-medication program did not
      increase the proportion of patients who were able to self-medicate on discharge
      from hospital. Compliance was improved by the program. On a proportional basis,
      the self-medication group made significantly fewer medication errors than the
      control group at 1-month follow-up (0.045 vs 0.086, P < .001). There were no
      significant differences in morale or medication knowledge between the SMP and
      control groups, although both groups made significant gains in knowledge about
      the names, administration times, and purposes of their medications from admission
      to follow-up (P < .001). CONCLUSIONS: A SMP can improve compliance in geriatric
      patients who are discharged to the community. Participation in a SMP does not
      improve patients' morale nor does it improve their medication knowledge more than
      pharmacy counselling alone. Participation in a SMP is unlikely to increase the
      probability that patients will be able to self-medicate on discharge. Cognitive
      factors limit patients' ability to self-medicate.

PMID- 8576507
TI  - Nutritional assessment: a primary component of multidimensional geriatric
      assessment in the acute care setting.
AB  - OBJECTIVE: To test the prognostic role of nutritional variables as a component of
      geriatric multidimensional assessment and to study the effect of hospitalization
      on nutritional status. DESIGN: Validation cohort study: multidimensional
      assessment on admission and at discharge and a weekly nutritional assessment.
      SETTING: General Medicine and Geriatrics wards in an acute-care university
      hospital. PATIENTS: A consecutive sample of 302 patients aged 79 +/- 6 years,
      range 70-96 years. MAIN OUTCOME MEASURES: Mortality, longstay (> 29 days), loss
      of lean body mass as expressed by a negative change in mid-arm muscle
      circumference (MAMC). RESULTS: Incidence of mortality, longstay, and decreased
      MAMC was 6.9%, 24.8%, and 64.2%, respectively. According to logistic regression
      analysis, mortality was independently predicted by preadmission dependency in at
      least one Activity of Daily Living (odds ratio = 2.08, confidence limits = 1.19
      3.65), clinical diagnosis of malnutrition (OR = 1.89, CL = 1.11-3.21), serum
      albumin < 3.5 g/dL (OR = 1.82, CL = 1.06-3.14). This predictive model allowed us
      to recognize 75% of the patients at risk of death by targeting 23% of the
      population. Longstay was independently predicted by stroke (OR = 1.54, CL = 1.01
      2.35), clinical diagnosis of malnutrition (OR = 1.41, CL = 1.04-1.93), and more
      than five comorbid diseases (OR = 1.39, CL = 1.01-1.94). Dependency in at least
      one ADL was the only independent predictor of decreased MAMC (OR = 1.71, CL =
      1.27-2.30). CONCLUSIONS: Nutrition variables are a cardinal component of
      multidimensional assessment in the acute-care setting. Nutritional status
      deteriorates during the hospital stay, mostly in physically dependent patients.

PMID- 8576508
TI  - A walking program for nursing home residents: effects on walk endurance, physical
      activity, mobility, and quality of life.
AB  - OBJECTIVES: To determine the effects of a 12-week walking program on walk
      endurance capacity, physical activity level, mobility, and quality of life in
      ambulatory nursing home residents who had been identified as having low physical
      activity levels and low walk endurance capacities. To determine the effects of 12
      versus 22 weeks of walk training on walk endurance capacity, physical activity
      level, mobility, and quality of life in ambulatory nursing home residents.
      DESIGN: Experiment 1: Residents of one nursing home campus were assigned to the
      walking program, and residents of a second campus were assigned to the social
      visit control group. Outcome measures were taken before and after 12 weeks.
      Experiment 2: Pretest/posttest with outcome measures taken before and, again,
      after 12 and 22 weeks of walking. SETTING: Two campuses of the Jewish Homes for
      the Aging in the Los Angeles area. PARTICIPANTS: Experiment 1: Nineteen of 22
      residents in the walking group completed the walking program, and 12 of 15
      residents in the control group completed the study. Experiment 2: Thirty of 41
      residents (from the two nursing homes) completed the 22-week walking program.
      INTERVENTION: Experiment 1: The walking program involved each resident walking
      with research staff at his/her self-selected walking pace, 5 days per week for 12
      weeks, for a maximum of 30 minutes per day; while the control group had weekly
      individual social visits, which lasted 30 minutes, from a research assistant.
      Experiment 2: All residents, those in both the walking and the control group,
      were offered the opportunity to complete 22 weeks of walking. MAIN OUTCOME
      MEASURES: Maximal walk endurance capacity, the resident's maximum walk time
      performed in a single day of walking (distance and speed also were measured);
      physical activity level based on time-sampled observations and physical activity
      monitors; mobility as measured with the Timed-Up-and-Go test, left handgrip
      strength, and Tinetti's Mobility Assessment; and quality of life as assessed with
      the Geriatric Depression Scale (a bodily pain scale) and the Dartmouth Primary
      Care Cooperative Information Project (COOP) physical work chart. RESULTS:
      Experiment 1: The walking group significantly improved their maximal walk
      endurance time by 77% and distance by 92%, with no significant change in walk
      speed; however, the control group showed no significant changes in these
      variables. There were no significant group by time interactions on measures of
      physical activity, mobility, and quality of life. Experiment 2: No further
      significant changes were found from 12 to 22 weeks in walk endurance capacity,
      physical activity, mobility, or quality of life. CONCLUSION: Twelve weeks of
      daily walking at a self-selected walking pace by ambulatory nursing home
      residents produced significant improvements in walk endurance capacity. No other
      significant changes were noted in physical activity level, mobility, or quality
      of life in either group after the intervention. Also, there were no side effects,
      such as increases in falls or cardiovascular complications, due to the walking
      intervention. Lengthening the walking program to 22 weeks produced no further
      significant changes in any outcome measures.

PMID- 8576509
TI  - Depression and disability in older people with impaired vision: a follow-up
      study.
AB  - OBJECTIVE: To determine the prevalence of depressive symptoms and their
      relationship to disability in older low vision patients. DESIGN: Panel study with
      2-year follow-up. PARTICIPANTS: Community-residing older people (N = 31).
      MEASUREMENTS: Geriatric Depression Scale, Community Disability Scale, and Snellen
      visual acuity. RESULTS: Twelve of 31 patients (38.7%) had GDS scores > or = 11 at
      baseline. Two years later, 10 of these 12 patients remained depressed, and three
      of the 19 (15.8%) previously nondepressed patients had become depressed.
      Depressed patients tended to be more disabled functionally than nondepressed
      patients at follow-up. The correlation of disability with depression and with
      vision were examined for the entire sample and revealed a strong correlation
      between disability and depression (r = .40; P = .013) compared with that of
      disability and vision (r = .34; P = .032) at baseline and at follow-up:
      depression (r = .68; P = .001), vision (r = .45; P = .006). There was no
      significant correlation between depression and vision at baseline (r = .06; P =
      .383), but there was a trend toward correlation at follow-up (r = .28; P = .067).
      CONCLUSION: Depressive symptoms are prevalent and persistent among low vision
      patients and appear more highly related to disability than is vision. The
      frequent occurrence of depression and the availability of effective treatment
      argue for its recognition and treatment as possible ways to reduce disability in
      older persons with low vision.

PMID- 8576510
TI  - The application of health care surrogate laws to older populations: how good a
      match?
AB  - OBJECTIVE: The Health Care Surrogate Act (HCSA) in Illinois has been proposed as
      a model for state laws naming surrogate medical decision-makers for those without
      advance directives (ADs). Our objective was to determine if the HCSA identifies
      the same surrogate as older persons would choose for themselves. If not, is the
      discrepancy between legally identified surrogate and preferred surrogate
      troublesome to respondents? Because it is documented that black Americans have a
      variety of family structures, some of which may not be reflected in the HCSA
      list, we also wished to determine if discrepancies between surrogates named by
      the law and those desired by patients are associated with black or white race.
      DESIGN, SETTING AND PARTICIPANTS: A convenience sample of 144 patients aged 65
      and older, without cognitive impairment, was interviewed at the geriatrics clinic
      of an academic medical center. MAIN OUTCOME MEASURES: Respondents without ADs who
      had a different stated choice for surrogate medical decision-maker than the
      surrogate defined by the Illinois HCSA, based on their existing family. RESULTS:
      Twenty-six percent of respondents without ADs chose a surrogate that differed
      from the surrogate defined by the HCSA. However, 67% of those with a different
      choice for surrogate than defined by law were not troubled by the discrepancy.
      The proportion of black subjects (25%) and white subjects (31%) who had surrogate
      discrepancies was not significantly different (P = .6). CONCLUSION: Because the
      Illinois HCSA named surrogates who would be agreeable to the majority of our
      respondents, it appears that it may be a useful model for state surrogacy laws.

PMID- 8576511
TI  - Clinical presentation and results of thrombolytic therapy in older patients with
      massive pulmonary embolism: a comparison with non-elderly patients.
AB  - OBJECTIVE: To assess the clinical presentation and effectiveness of thrombolytic
      therapy in older patients suffering from massive pulmonary embolism. DESIGN:
      Analysis of a previously reported study of patients with massive pulmonary
      embolism using a dichotomous classification of age. SETTING: A medical intensive
      care unit in one hospital center. PARTICIPANTS: All subjects had massive
      pulmonary embolism as evidenced by scintigraphic and/or angiographic assessment.
      The 54 patients included in this study were divided into two groups according to
      age: 28 patients were less than 75 years old and 26 patients were 75 years old or
      older. INTERVENTION: All patients received a bolus regimen of single-chain
      recombinant tissue-type plasminogen and were subsequently treated by heparin and
      warfarin. MEASUREMENTS: Clinical symptoms at admission, resolution of
      scintigraphic vascular obstruction, death rate, hemorrhagic complications,
      recurrent pulmonary embolism, and long-term follow-up were compared between both
      groups. RESULTS: Clinical symptoms at admission were similar in both groups. The
      mean absolute improvement in the lung scan perfusion defect, the rate of major
      bleeding, and the long-term evolution were not statistically different between
      older and younger patients. CONCLUSION: Clinical symptoms, including hemodynamic
      condition, did not differ between elderly and nonelderly patients suffering from
      massive pulmonary embolism. Old age should not preclude thrombolytic therapy in
      massive pulmonary embolism, provided there is no other contraindication for
      thrombolytic treatment.

PMID- 8576512
TI  - Probable adverse drug reactions in a rural geriatric nursing home population: a
      four-year study.
AB  - OBJECTIVE: To quantitate probable adverse drug reactions (ADRs) in a geriatric
      nursing homes population. DESIGN: A repeated measures prospective study. SETTING:
      Two nursing home populations in rural Georgia. PATIENTS: All 332 residents
      present for 30 or more days over a 4-year period. MEASUREMENT: Admission and
      monthly drug regimen review for each resident, Naranjo algorithm assessment of
      each ADR, with monthly reports to attending physicians and follow-up within the
      next month. RESULTS: There were 444 probable ADRs in 217 of 332 residents (67.4%)
      during this period. The 217 residents had a mean 1.9 +/- 1.3 probable adverse
      drug reactions (range, 1-9). The ADR group differed statistically from the rest
      of the population only in the number of drugs per patient (7.8 +/- 2.6 vs 3.3 +/-
      1.3), which was almost twice the number of active problems present in both the
      ADR (4.0 +/- 0.9) and non-ADR populations (3.8 +/- 1.4). The organ systems most
      commonly involved in the 444 ADRs observed were cardiovascular (188), central
      nervous system (129), gastrointestinal (82), endocrine (41), immune (17),
      hematologic (7), pulmonary (6), and renal (5). The drugs most commonly implicated
      in ADRs were, in decreasing order, diuretics, antipsychotics, anxiolytics,
      potassium supplements, digoxin, NSAIDs, insulin, theophylline, H2-receptor
      antagonists, antiinfectives, anticonvulsants, and thyroid supplements. There were
      39 multiple drug ADRs in 34 patients. In decreasing order the drug classes in
      multiple ADRs were CNS depressants, antihypertensives, potassium-altering
      therapy, and NSAIDs. Numerous patients had repetitions of the same ADR,
      especially with antipsychotics, NSAIDs, and insulin. CONCLUSIONS: ADRs are a
      common occurrence in a geriatric nursing home population, and may be related to
      inadequate attention to the patients history as well as to unrealistic
      therapeutic endpoints.

PMID- 8576513
TI  - Depression and medical illness in late life: report of a symposium.
AB  - The high comorbidity of medical illnesses and late life depression poses both
      challenges and opportunities. Challenges in assessment techniques, diagnosis, and
      specific prognosis affect clinical care and research methodology alike. However,
      investigations that turn this vexing "confound" into research questions may prove
      fruitful. For clinicians working with older persons, recognizing the prognostic
      import of comorbid medical illnesses in late-life depression is essential to
      treatment planning. This comorbidity also poses difficulties in diagnosing
      depression inasmuch as symptoms of the medical conditions may overlap with those
      of an affective disorder. Symptom assessments must strike a balance between
      overly inclusive (e.g., mistakenly treating the psychomotor slowing of
      Parkinson's disease as depression) and overly exclusive (e.g., erroneously
      dismissing the patient's mood symptoms as "understandable"). Clinicians also
      should be sensitive to the broad range of symptomatic presentations with varying
      severities of both mood and medical disorders, as exemplified by variability
      across treatment settings. For researchers, similar issues are of relevance in
      planning investigative strategies. Consideration should be given to the
      following: 1. Case identification is a crucial first step; the approach to
      depressive symptoms potentially confounded by medical illnesses must be defined
      explicitly. Choice of an inclusive approach avoids premature exclusion of
      relevant phenomena; exploratory analyses can examine the effects of other
      approaches to the relationships of interest. 2. The use of similar research
      instruments across sample sites would greatly facilitate comparisons of results.
      Each subject group offers its own "leverage" for answering particular questions.
      Psychiatric inpatients will highlight the contributions of severe psychopathology
      (useful, for example, in identifying biologic markers). Medical inpatients are
      well suited to studies examining validity of different approaches to case
      identification, investigating health service utilization, or highlighting the
      contribution of acute, severe, life-threatening medical disorders to affective
      illness. Long-term care residents lend themselves to issues that benefit from
      compression of health processes over time. Medical outpatients have many
      advantages regarding generalizability and public health significance. Community
      samples are needed to determine the biases of all the above groups, which are
      each defined by service utilization. 3. Study of the relationships between
      depression and medical illness may further understanding of pathogenic mechanisms
      in late life mood disorders. Research questions might be guided by the
      biopsychosocial conceptual context described above. On the one hand, this context
      demands multidimensional study methodology to identify the routes by which
      medical illness influences depression in particular patient groups. Multivariate
      models should examine direct and indirect effects of medical illness on
      depression while, at the same time, considering intervening variables such as
      functional disability, personality, and social support. Guided multiple
      regressions or structural equation modeling will allow for determination of
      strengths of associations. 4. At the same time, and of particular importance if
      complex multivariate analyses are used, specific theoretic models should help
      direct focused investigations. The development and testing of such models is a
      major challenge that should be addressed by current research. Finally, from a
      societal perspective, the comorbidity of depression and medical illness likely
      has a tremendous impact on both health and health care delivery for older adults.
      Further study is needed to identify more specific approaches to treatment. Yet
      existing data clearly support a policy of routine psychiatric assessment of older
      people in general medical settings...

PMID- 8576514
TI  - The National Institute on Aging at its twentieth anniversary: achievements and
      promise of research on aging.
AB  - As these distinguished speakers demonstrate, the research community should take
      enormous pride in its many achievements to date, as well as in the scientific
      break-throughs that appear to be just on the horizon. However, existing gaps in
      our knowledge about the aging process certainly will require a great deal more of
      our attention. As former NIA director Robert N. Butler, MD, cautioned in the
      symposium's opening panel, "We remain ill-prepared for the 21st Century when
      population aging will become unprecedented. We already feel the impact of a
      revolution in longevity that has added 28 years to the life expectancy of
      Americans since the beginning the century. But we are not prepared for the baby
      boomers--the largest generation in U.S. history and one-third of our present
      population, the first of whom will turn 65 in 2011. "I regard the baby boomers as
      a generation at risk. We still devote relatively few resources to understanding
      the biology of aging. Although we have made progress in understanding the
      pathogenesis of Alzheimer's disease, we are a long way from a cure. While we have
      some insights into the demography of aging, the social impact of population aging
      upon society and, in turn, the psychosocial experiences of growing older, we are
      a long way from understanding the full implications of any of these." Maintaining
      and improving the health and well-being of older people will be among the
      greatest social challenges of the next century. Research into aging and the
      diseases common to older people undoubtedly holds the key to addressing the
      health and social needs of older people and reducing the risk factors driving the
      increased and costly need for long-term care. At the same time, the effects of
      downsizing and cost constraints in all segments of today's society challenge our
      ability to address these needs. Although scientists today face serious challenges
      to completing the work that research already has generated and to initiating new
      projects, we are energized by the potential for widespread benefit. Using that
      energy, in 20 years' time we should expect to look back with the same sense of
      accomplishment and ahead with the same enthusiasm for achievements yet to come.

PMID- 8576515
TI  - Physical activity and older people: a walk a day keeps the doctor away.

PMID- 8576516
TI  - Age-associated memory impairment and Alzheimer's disease.

PMID- 8576517
TI  - Brief screening for depression.

PMID- 8576518
TI  - Preoperative assessment of older adults.

PMID- 8576519
TI  - Diagnostic testing for dementia in patients with Parkinson's disease.

PMID- 8576520
TI  - An abbreviated Mini-Mental State Exam for medically ill older adults.

PMID- 8576521
TI  - Could aspirin/NSAID treatment preserve independence and decrease the need for
      institutionalization of older rheumatoid arthritis patients.

PMID- 8576522
TI  - Temporal progression of hippocampal atrophy and apolipoprotein E gene in
      Alzheimer's disease.

PMID- 8576523
TI  - Comments on the executive control of clock-drawing.

PMID- 8576524
TI  - Health screening of older people: a rural African experience.

PMID- 8576525
TI  - Alzheimer's disease as a metaphor for contemporary fears of aging.

PMID- 8576526
TI  - Primary carcinoma en cuirasse.

PMID- 8576527
TI  - Testing the field of vision: a primary responsibility.

PMID- 8576528
TI  - Urgent challenges to optometric education.

PMID- 8576529
TI  - An open and shut case.

PMID- 8576530
TI  - Air Force optometry.

PMID- 8576531
TI  - Clinical evaluation of five portable tonometers.
AB  - BACKGROUND: Intraocular pressure (IOP) measurements obtained with five
      commercially available portable tonometers (Keeler Pulsair 2000, Tomey Pro-Ton,
      Tono-Pen XL, Perkins, and Shiotz) were compared to IOPs measured with a Goldmann
      tonometer in order to predict whether instrument accuracy justified substitution
      of a portable instrument for the Goldmann in all or specific circumstances.
      METHODS: A total of 31 patients (59 eyes) were assessed. The order of techniques
      was random except that in each case Goldmann tonometry was performed first and
      Shiotz tonometry was performed last. Examiners were masked to all other IOP
      measurements. Correlation and regression analyses were used to predict Goldmann
      IOP from the other portable tonometer readings. In addition, the difference in
      pressure readings was compared to mean pressure readings. RESULTS: Comparisons of
      means, correlations, regression equations, and box plots of difference scores
      were performed to determine which techniques were more accurate. The results
      varied slightly depending on the method used. All IOPs obtained with portable
      tonometers showed significant correlation and regression equations compared to
      the Goldmann IOPs. The correlation ranged from (r = 0.75) for the Keeler Pulsair
      to (r = 0.66) for the Schiotz. Three tonometers (Tono-Pen, Schiotz, and the Pro
      Ton) showed a small significant underestimation of the Goldmann IOPs.
      CONCLUSIONS: All portable tonometers were able to accurately predict Goldmann
      IOPs. While three of the tonometers were found to underestimate Goldmann IOP on
      average, these results can be corrected by either adding the underestimation or
      by using the best fitting regression equation.

PMID- 8576532
TI  - Pupillary dilation and its effects on automated perimetry results.
AB  - BACKGROUND: The effects of miotic drugs on visual field sensitivity have been
      well documented, but few studies have reported the effects of active pupillary
      dilation on visual field sensitivity. Since visual field testing is sometimes
      performed when a patient is undergoing pupillary dilation for fundus examination,
      the effects of active pupillary dilation is of concern to today's optometrist.
      METHODS: The effects of active pupillary dilation on automated static threshold
      perimetry were studied in 23 normal subjects using the Humphrey Field Analyzer
      and the 30-2, StatPac, and FastPac programs. Baseline automated perimetry was
      performed on both eyes of each subject with the Humphrey Field Analyzer. On a
      separate visit, automated perimetry was performed on both eyes of all subjects
      while each eye was undergoing active pupillary dilation. Baseline and dilated
      visual field parameters were compared. RESULTS: A decrease in foveal threshold of
      1.95 decibels (p = 0.0081), a mean deviation loss of 1.15 decibels (p = 0.0001),
      a decrease in short-term fluctuation (SF) of 0.19 decibels (p = 0.0423), and a
      decrease in the SF2 of 0.56 decibels (p = 0.0374) were found in the dilated
      fields as compared with the baseline visual fields in the first eye tested. A
      decrease in foveal threshold of 2.56 decibels (p = 0.0081) and a mean deviation
      loss of 1.43 decibels (p = 0.0001) were found in the dilated fields as compared
      with the baseline visual fields in the second eye tested. CONCLUSIONS: These
      findings indicate that active pupillary dilation in healthy subjects produces
      statistically significant differences, although these differences may not be
      clinically significant. To ensure repeatable visual fields, consistent pupil
      diameter should be controlled during serial visual field testing.

PMID- 8576533
TI  - Clinical implications of intra- and inter-reader agreement in four different
      automated visual fields.
AB  - BACKGROUND: This study was designed and conducted to examine the degree of inter-
      and intra-reader agreement when four readers evaluate visual fields in patients
      known to have glaucoma and patients known to not have glaucoma. METHODS: Fifty
      three patients known to have glaucoma and 60 patients known not to have glaucoma
      were selected randomly from a population at the University of Alabama at
      Birmingham School of Optometry. Four visual fields were performed on each
      patient, non-dilated, with the proper correction in place. The fields were
      performed on three different instruments by technicians who were unaware of the
      diagnostic status of the patient. Four independent (blinded) clinicians read the
      visual fields and judged them as: "glaucoma field defect," "no glaucoma field
      defect," and "poor reliability-cannot judge." RESULTS: Statistical analysis
      revealed that a single reader's interpretation of four different types of visual
      fields are very different from, are poorer than, and are more consistent than are
      the four readers' interpretations of a single type of visual field. The analysis
      also shows that the readers consistently underestimated the number of glaucoma
      patients with one instrument and overestimated the number with another.
      CONCLUSIONS: This results suggest that a single visual field will discriminate
      patients with glaucoma with an accuracy in the 70 to 75 percent range. For one of
      the instruments, the shorter protocol was almost as effective in discriminating
      glaucomatous fields as the longer protocol. This study also suggests that
      repeating the visual fields or analysis of a single field by two readers improves
      reliability.

PMID- 8576534
TI  - The illuminated high contrast macular grid: a pilot study.
AB  - BACKGROUND: Analysis of visual disturbances in the central 10 degrees provides
      valuable data for the low vision clinician. Amsler grid testing in the visually
      impaired can be poorly visible and it can be difficult to transcribe results.
      Automated perimeters will accurately map retinal defects, but the equipment is
      expensive and this technique is time consuming. An Amsler grid was modified using
      principles of luminance and contrast to improve its accuracy, and its efficacy
      was compared to an automated perimeter. METHODS: Eighteen visually impaired
      patients (28 eyes) were prospectively evaluated at the Emory Low Vision
      Laboratory. Each patient had three central threshold visual field tests:
      automated perimetry (Humphrey model 690), conventional Amsler Grid, and
      Illuminated High Contrast Macular Grid (IHCMG). The Humphrey central 10-2
      threshold automated visual field examination was performed to map the patient's
      retinal function. RESULTS: The Humphrey analysis identified (mean +/- one
      standard deviation) 2.4 +/- 1.4 defects per patient with an average percent
      defect area of 33.4 +/- 14.8 degrees. The IHCMG technique was not significantly
      different from the Humphrey technique for identifying the number of defects (2.25
      +/- 1.5) (p > 0.05) or the percent defect area (26 degrees +/- 20 degrees) (p >
      0.05). The conventional Amsler grid technique significantly under-evaluated the
      retinal defects compared to the Humphrey analysis of the number of defects (p <
      0.01) and percent area of defects (p > 0.001). CONCLUSIONS: The IHCMG technique
      can be used as a simple, rapid and accurate analysis of the central 10 degrees
      visual field in the low vision patient.

PMID- 8576535
TI  - Clinical alternative for reducing the time needed to perform automated threshold
      perimetry.
AB  - BACKGROUND: Automated threshold perimetry is an important test used to diagnose
      and monitor open angle glaucoma. Unfortunately, the test can be tedious and
      demands that a patient concentrate for up to fifteen minutes or more per eye to
      achieve useful results. Many individuals are not capable of fixating for extended
      periods, and the reliability of the automated threshold test consequently
      suffers. This paper explores alternative methods to perform automated threshold
      perimetry so that the time required for testing is reduced while the clinical
      impact of performing abbreviated tests is minimized. METHODS: Several different
      versions of a central automated threshold perimetry test were run on a
      cooperative, normal individual utilizing a Humphrey Field Analyzer. One field was
      run on consecutive days in one eye only. The 24-2 and 30-2 test patterns were
      performed using the standard threshold format, FastPac, and certain modifications
      (involving the short-term fluctuation monitor and the fixation monitor) to
      measure the time required for the test to be performed and monitor any changes in
      the global indices as measured by the tests. RESULTS: The 30-2 automated
      threshold test requires about 13 minutes to perform while a similar central
      threshold test, the 24-2 test, run in a modified format (without the short-term
      fluctuation monitor and/or the fixation monitor) was performed in about five
      minutes. CONCLUSIONS: There are several methods that may be used to reduce
      perimetric testing time without compromising significantly the reliability of the
      diagnostic information. Reduced testing time may enable the clinician to obtain
      reliable fields in certain patients whose data are deemed unreliable when
      performing lengthier tests. The clinician must decide which data may be lost when
      testing time is reduced since clinical decision-making is inevitably affected
      whenever clinical data is not gathered.

PMID- 8576536
TI  - Comparing threshold visual fields between the Dicon TKS 4000 automated perimeter
      and the Humphrey Field Analyzer.
AB  - BACKGROUND: The automated perimeter is becoming the instrument of choice in the
      analysis of the visual field. There are a number of different perimeters in use
      and it can be difficult to compare results from different instruments. The
      purpose of this study was to compare visual field threshold measurements
      determined by the Humphrey Field Analyzer and the Dicon TKS 4000. METHODS: This
      study provided a statistical comparison of field test results from the Dicon TKS
      4000 Automated Perimeter (program number 9) and the Humphrey Field Analyzer (30-2
      threshold using FastPac). Central 30 degree, 76 point full threshold fields were
      performed on 20 non-dilated optometry students (age range 21 to 32 years, mean
      age 25.1 years) using both instruments. For the purpose of statistical analysis,
      the visual field was divided into 24 sectors, each measuring 10 degrees by 10
      degrees. The mean threshold value of each group of points was compared between
      instruments. RESULTS: A difference was found between instruments (significant at
      P&0.0001) for 19 of 24 sectors. In addition, the Humphrey Field Analyzer
      threshold values were consistently higher (average difference 2.47 dB) than the
      Dicon values. Each subject was tested twice on each instrument; both instruments
      showed high test-retest correlations: 0.970 for the Humphrey and 0.971 for the
      Dicon. Test administration times were comparable (average 435.2 seconds for the
      Humphrey Field Analyzer and 430.2 seconds for the Dicon), although the Dicon
      averaged 41.5 fewer presentations tested per examination. Fixation losses were
      higher with the Dicon instrument. CONCLUSIONS: A practitioner may be reluctant to
      directly compare test results between the two instruments since they produce
      threshold values of statistically significant differences. The Dicon TKS 4000 was
      subjectively preferred over the Humphrey Field Analyzer by most subjects.

PMID- 8576537
TI  - Retinal nerve fiber layer defects and microtalc retinopathy secondary to free
      basing "crack" cocaine.
AB  - BACKGROUND: There have been several reports in the literature documenting ocular
      manifestations of cocaine abuse. None have discussed the potential retinal
      complications stemming from cocaine inhalation. METHODS: Approximately 60
      patients with a history of free-basing "crack" cocaine were examined at the
      Optometry Clinic. Threshold visual field testing and fundus photographs were
      obtained and later reviewed. RESULTS: Microtalc retinopathy and associated
      retinal nerve fiber layer "rake" or "slit" defects were detected exclusively in
      patients who had free-based "crack" cocaine. Some of these patients manifested
      visual field changes that mimic glaucoma. Several cases are presented that
      demonstrate the findings typical of those observed in the patients examined at
      the Optometry Clinic. CONCLUSIONS: Microtalc retinopathy and associated glaucoma
      like retinal nerve fiber layer defects indicate the presence of permanent
      microvascular changes in the eyes, as well as the lungs, brain, and probably
      other peripheral organs. Optometrists should be aware of these new findings in
      order to properly manage patients who free-base "crack" cocaine.

PMID- 8576539
TI  - Immunoregulatory effects of a synthetic monosaccharide.
AB  - Investigative attempts to identify novel therapy for inflammatory connective
      tissue diseases continue to evolve. Amiprilose hydrochloride (amiprilose HCl) is
      a synthetic carbohydrate shown to have anti-inflammatory effects in animal models
      of inflammatory arthritis and in a multicenter clinical trial. Interleukin-1 (IL
      1) is an important mediator of immune regulation, inflammation and joint
      destruction in arthritis. In the present study, the effects of amiprilose HCl on
      IL-1 activity, production and receptor distribution were investigated. Drug
      effects on IL-2 production and receptor distribution on lymphocytes were also
      explored. Potential regulation of IL-1 activity was determined by monitoring the
      effects of amiprilose HCl on IL-1 stimulated proliferation of murine thymocytes
      and human synovial cells. Inhibitory effects on IL-1 beta and IL-2 production by
      stimulated human peripheral blood monocytes were measured by ELISA and lymphocyte
      IL-1 beta and IL-2 receptor distribution were analyzed by flow cytometry. The
      results from in vitro studies demonstrated that low concentrations of amiprilose
      HCl (1-100 micrograms/ml) stimulated thymocyte proliferation and enhanced the
      proliferative response of IL-1 stimulated human synovial fibroblasts. IL-1 beta
      production in cultures of human peripheral blood monocytes was significantly
      decreased after exposure of the cultures to varying doses of amiprilose HCl as
      determined by ELISA. Exposure of mitogen activated human peripheral blood
      lymphocytes to amiprilose HCl resulted in decreased IL-2 production at high
      concentrations of drug as compared to control. However, at doses of amiprilose
      HCl previously found to stimulate thymocyte proliferation (1-10 micrograms/ml),
      increased levels of culture supernatant IL-2 were observed. No amiprilose HCl
      mediated changes in lymphocyte IL-1 beta or IL-2 receptor expression were
      observed. The regulatory effects of amiprilose HCl on cytokines support the
      potential of this drug as a therapeutic agent for the treatment of inflammatory
      arthritis.

PMID- 8576538
TI  - Antimetastatic effect of immunization with liposome-encapsulated tumor cell
      membrane proteins obtained from experimental tumors.
AB  - Immunization of C57BL/6 mice with tumor-derived membrane-proteins encapsulated in
      sized liposomes (0.2 microgram/mouse) and composed by phosphatidylcholine or
      sphingomyelin, significantly reduced the mean values of spontaneous lung
      metastasis from both B16 (0.7 +/- 0.5 and 1.2 +/- 0.6, respectively) and 3LL (4.8
      +/- 2.5 and 7.2 +/- 4.1, respectively) tumors, with respect to control (HEPES)
      groups (4.8 +/- 1.1 and 19.0 +/- 4.4, respectively). However, no significant
      antimetastatic effect was observed using free tumor-derived proteins (2
      micrograms/mouse) or liposome vehicle alone. Specific humoral immune response
      after the vaccination was studied by flow cytometry of tumor cells incubated with
      a pooled sample from each group of immunized mice and FITC-conjugate antimouse
      immunoglobulins. The results showed that the highest number of positive tumor
      cells was identified using sera from immunized mice with sized liposomes
      encapsulating tumor-derived proteins whereas the immunization with the protein
      fraction in free form failed to induce this effect. In addition, an increased
      cytotoxicity towards 3LL and B16 tumor cells can also be observed when tumor
      cells were incubated with spleen effector cells plus specific immunosera. In
      conclusion, our results show that antitumor active vaccination, using sized
      liposomes as adjuvants, induces an antitumor host response and a significant
      inhibition of tumor progression.

PMID- 8576540
TI  - Bleomycin and FK 565 enhance the release of GM-CSF from LPS-stimulated BALB/c
      peritoneal macrophages.
AB  - The anti-tumour antibiotic Bleomycin, the experimental immunostimulatory
      tripeptide FK 565, and the immunosuppressive agent Cyclosporin A were examined
      for their in vitro effects on the release of the haemopoietic cytokine
      Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) from LPS stimulated
      BALB/c adherent peritoneal macrophages. FK 565 and Bleomycin produced an increase
      in GM-CSF release indicating that these agents are capable of stimulating
      peritoneal macrophage populations. Cyclosporin A was found to have no effect.

PMID- 8576541
TI  - Effects of the angiotensin converting enzyme inhibitor captopril on experimental
      autoimmune encephalomyelitis.
AB  - Angiotensin converting enzyme (ACE)1 mediates inflammation, participates in T
      cell stimulation by certain antigenic peptides, and influences the permeability
      of the blood brain barrier (BBB). ACE is elevated in multiple sclerosis (MS), an
      autoimmune disease of the central nervous system (CNS), characterized by
      increased BBB permeability. ACE inhibitor captopril suppresses certain immune
      functions and inhibits inflammatory or autoimmune diseases. We studied the effect
      of captopril on Lewis rat EAE, an animal model of MS. Fourteen rats with EAE were
      treated with captopril 30 mg/kg daily from immunization to day 21 post
      immunization, and compared with 14 untreated rats. Severity scores and lymphocyte
      reactivity to myelin basic protein and mitogen were measured. There was a
      statistically significant (p < 0.05) difference between the mean and cumulative
      clinical scores of captopril-treated and untreated animals. Lymphocytes from
      captopril treated EAE rats at the peak of disease severity had diminished
      responses to MBP and concanavalin A. The data suggest a significant beneficial
      effect of captopril in Lewis rat EAE. Further studies including other inhibitors
      of ACE or of other peptidases with immune, inflammatory or BBB role, may identify
      potentially valuable immunopharmacologic agents.

PMID- 8576542
TI  - Survival to lipopolysaccharide, cytokine release and phagocyte functions in mice
      treated with different total parenteral nutrition regimens.
AB  - Effects on host defenses of Total Parenteral Nutrition (TPN) with long- (LCT) and
      medium-chain triglycerides (MCT) were studied. Survival to lipopolysaccharide
      (LPS) challenge, blood clearance of Escherichia coli, in vivo and in vitro
      production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)
      were investigated. In BALB/c mice, LCTs produced a 25% reduction in mortality,
      compared with controls. TPN performed with a LCT plus MCT mixture reduced
      mortality by 50%. Spasms appeared after 18 h and 12 h respectively in mice
      treated with LCT-MCT mixture or LCTs alone, respect to controls (8 h). The LCT
      MCT mixture produced a 67% blood clearance of E. coli after 1 h, while the
      treatment with LCTs alone had no significant effects compared to controls (about
      40%). The LCT-MCT mixture induced a 50% increase in chemiluminescence respect to
      controls. A 33% increase was observed in rats treated with LCTs alone. TNF-alpha
      serum levels after challenge with LPS were not modified by any of the
      triglycerides or their combinations. IL-6 increased by 43% with LCT-MCT mixture
      and by 39% with LCTs alone versus controls. After a 3 h in vitro treatment with
      LCTs, human monocytes were stimulated to release TNF-alpha at levels higher than
      those stimulated with the LCT-MCT mixture, and respect to controls. In contrast
      after 3 h the stimulation with LCT-MCT mixture induced a higher IL-6 release than
      controls and cells stimulated with LCTs alone, or with LPS.

PMID- 8576543
TI  - In vivo capsaicin treatment inhibits rat NK cell cytotoxic functions.
AB  - The direct and indirect interactions between the nervous system and its
      transmitters with NK cell cytotoxic functions has been evaluated in the rat by
      using the neurotoxin capsaicin (8-methyl-N-vanillyl-6-nonenamide). When
      administered to neonatal rats, capsaicin (50 mg/Kg in 10% ethanol and 10% tween
      80 at 2 days of age) interferes with the synthesis and intraneuronal transport of
      peptides by causing irreversible degeneration of c fiber afferent nerves.
      Capsaicin treatment resulted in a marked inhibition of NK and ADCC activities
      both in the spleen and peripheral blood. Inhibition was already evident on day 15
      after treatment and persisted until day 90 in the spleen; at this time NK
      cytotoxicity in the peripheral blood returned to control levels. The inhibitory
      effect of capsaicin treatment on peripheral blood NK and ADCC activities was
      associated with changes in NK cell number evaluated as percentage of cells with
      an LGL morphology and expressing the NK-RP1 cell surface receptor. LGL numbers
      did not always correlate with the percentage of NK-RP1+ cells suggesting that
      capsaicin may interfere with maturation of lytic effector cells. Overall these
      results indicate a direct influence of the nervous system on natural immune
      cytotoxic functions.

PMID- 8576545
TI  - Modification of actin in peritoneal macrophages after diazepam treatment.
AB  - We have investigated the effect of therapeutic doses of diazepam (7
      micrograms/mouse) on the association of actin with the macrophage cytoskeleton
      using cytochemical and morphological methods. Results obtained indicated that
      diazepam was able to modulate the content of actin in macrophages; such an effect
      proved to be time-dependent. After fixation and staining for indirect
      immunofluorescence with actin antibody, peritoneal macrophages from mice treated
      for short time with diazepam, showed a fluorescent intensity increase compared to
      control mice. The fluorescent intensity augmented reaching peak value within 14
      days of treatment. Afterwards, this value dropped below control value for mice
      that underwent longer treatments. In the in vitro experiments concentrations of
      10(-5) M, diazepam inhibited a well cell spread and a lower amount of actin after
      15 min of incubation was also revealed. These results suggest that administration
      of diazepam in vivo plays a role in both the nonspecific and specific immune
      response, producing in the macrophages a reorganization process of
      microfilaments.

PMID- 8576544
TI  - Evidence for a dual effect of acebutolol, a beta blocker, on the mouse humoral
      immune response.
AB  - Acebutolol induces transient polyclonal B cell activation in C57B1/6 mice but
      down-modulates the spontaneous polyclonal activation of NZBxNZW lupus mice. The
      immunomodulatory effects of this beta-blocker were studied in C57l/6 mice
      injected with LPS or immunized with sheep red blood cells. The effect of
      acebutolol on the polyclonal activation of lymphocytes induced by LPS was also
      investigated in heterozygous and nu/nu C57BL/6 mice. Finally, the direct effect
      of acebutolol on spleen cells was studied in vitro. Acebutolol treatment for 15
      days (50mg/kg/day) inhibited the polyclonal activation of lymphocytes induced by
      LPS in C57BL/6 and in C57BI/6 nu/nu mice, but increased the humoral response to
      sheep red blood cells in C57Bl/6 mice. Moreover, spleen cells from C57Bl/6 mice
      treated for 15 days with acebutolol showed an increased number of CD5+ and CD4+
      lymphocytes, as well as an increased reactivity to concanavalin A but not to LPS.
      In vitro, acebutolol at 10(-5)-10(-7) M induced an increased reactivity of spleen
      cells from naive mice to concanavalin A, whereas it did not affect the B cell
      responsiveness to LPS. These results indicate that acebutolol modulates both T
      cells and non T-cells in the immune system.

PMID- 8576546
TI  - Single dose parenteral hyposensitization to poison ivy urushiol in guinea pigs.
AB  - Studies were carried out in guinea pigs to evaluate the potential for single dose
      hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by
      topical application of 1 mg of poison ivy urushiol to the back of the neck. In
      the first series of studies, three different analogs of poison ivy urushiol were
      studied: 1) a mixture of pentadecyl and heptadecyl catechols (PDC/HDC), the
      saturated side chain analog of the natural urushiol mixture; 2) a mixture of the
      diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the
      saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac).
      Each of these compounds was administered as 5 mg of the free catechol i.m. each
      week for three weeks. A vehicle group received only corn oil injections.
      Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at
      1 and 5 weeks post-treatment. PDC/HDC Ac induced a marked reduction in both the
      incidence and the severity of lesions induced by PIU at both 1 and at 5 weeks
      post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and
      were less effective than PDC/HDC Ac at 1 week post-treatment. In a second series
      of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and
      multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac
      intramuscularly each week for 4 weeks, while another treatment group received a
      single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were
      also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac
      was only modestly effective, with some reduction of severity of lesions at the
      higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the
      incidence and the severity of the lesions at all challenge doses were reduced. In
      the multiple dose group, the incidence and severity of lesions are reduced at 1
      week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but
      were not significantly different from the single dose group. These findings
      indicate that the diacetate ester of PDC/HDC is an effective hyposensitizer to
      poison ivy urushiol, and that this hyposensitization can be reasonably
      accomplished in a single dose treatment regimen.

PMID- 8576548
TI  - Effect of mechlorethamine on SRBC-induced secondary antibody response in mice.
AB  - The effect of low-dose mechlorethamine (5 micrograms/kg) on secondary humoral
      response to sheep red blood cells (SRBC), depending on time of exposure to the
      drug in relation to priming and challenge was studied in Balb/c mice. It was
      found that mechlorethamine in a dose of 5 micrograms/kg stimulated primary
      humoral response to SRBC resulting in the increased number of the plaque forming
      cells (PFC) and hemagglutinin titre (19S + 7S). However, this effect waned 10
      days after immunization. On the other hand, the same mechlorethamine dose
      potentiated secondary humoral response to SRBC and increased the number of PFC
      and anti-SRBC hemagglutinin titres (notably 7S), which was due to the challenging
      antigenic stimulus. In each immunization, mechlorethamine administration
      prolonged the potentiating effect of the drug on anti-SRBC hemagglutinin titre.
      When mechlorethamine was administered to the mice only after priming, the number
      of PFC increased, but anti-SRBC hemagglutinin titre (7S) remained unchanged. This
      was likely due to the fact that mechlorethamine administered after priming
      increases the number of long-lived lymphocytes B, which in turn affect secondary
      humoral response.

PMID- 8576547
TI  - The effect of p-chloroaniline on leucocytes of sheep peripheral blood under the
      migration-inhibition test conditions.
AB  - Toxic and immunotoxic effects of p-chloroaniline--a metabolite of herbicide
      monolinuron--were investigated in peripheral blood leucocytic suspensions of five
      sheep using a migration-inhibition test. The toxic effect of p-chloroaniline was
      recorded at concentrations 1.0 to 0.1 mg.ml-1 and the immunotoxic one at
      concentrations 0.01-0.001 mg.l-1. The toxic effect was demonstrated by total
      inhibition of leucocyte migration. The immunotoxic effect, determined as
      mitogenic activation of leucocytes by phytohemagglutinin, concanavalin A and
      lipopolysaccharide, was detected at 10 to 100-fold lower concentrations of p
      chloroaniline than those which resulted in toxic effects.

PMID- 8576549
TI  - Parasite escape mechanisms: the role of Leishmania lipophosphoglycan on the human
      phagocyte functions. A review.
AB  - Protozoan parasites of the Leishmania genus are the causative agents of important
      diseases in humans and animals. During their life cycle in vertebrate hosts,
      protozoa are able to live and proliferate within phagolysosomes of host
      phagocytic cells. The capacity to live in this hostile environment is likely due
      to the cell surface glycoconjugate expression. In particular, lipophosphoglycan
      (LPG), a major surface glycoconjugate of Leishmania promastigotes, has been
      reported to play an active role in protecting parasites within phagolysosomes via
      the impairment of killing mechanisms. In this review, the authors emphasize some
      novel LPG-mediated escape mechanisms of promastigotes from human phagocyte
      responses, such as the impairment of oxidative burst and of chemotactic activity.
      In the light of these findings, the knowledge of biological actions of LPG may be
      useful in order to prepare a vaccine against human leishmaniasis, using LPG
      defective avirulent mutant strains.

PMID- 8576550
TI  - The ketogenic diet: Fa(c)t or fiction.

PMID- 8576551
TI  - The neuronal ceroid-lipofuscinoses.
AB  - The neuronal ceroid-lipofuscinoses, a group of progressive neurodegenerative
      diseases in children and in adults, have now been recognized for some 90 years,
      and the childhood forms represent one of the largest groups of progressive
      neurodegenerative diseases in children. Apart from a core group of major clinical
      forms-the infantile, the late-infantile, the juvenile, and the adult forms-
      numerous atypical patients afflicted with neuronal ceroid-lipofuscinosis have now
      been identified, constituting 10% to 20% of all patients with neuronal ceroid
      lipofuscinosis. These "atypical" patients have, over the past 10 years, prompted
      the suggestion of 15 atypical variants or minor syndromes, many of them
      displaying the lipopigments of classic curvilinear and fingerprint
      ultrastructure, but others displaying granular osmiophilic deposits. The former
      lipopigments contain the subunit C of the mitochondrial adenosine triphosphate
      synthase, but lipopigments of the granular osmiophilic deposits including the
      classic infantile type Santavuori-Haltia, apparently do not, the latter type
      exhibiting sphingolipid activator proteins. The nosologic significance of both
      the subunit C of the adenosine triphosphate synthase and the sphingolipid
      activator proteins, although they make up a considerable amount of the crude auto
      fluorescent lipopigments in neuronal ceroid-lipofuscinosis, is still unclear. In
      spite of numerous pathogenetic principles invoked, such as a defect in lipid
      peroxidation, abnormalities of dolichols and dolichol phosphates, and defects in
      protease inhibitors, precise pathogenesis and etiology of the neuronal ceroid
      lipofuscinoses remain elusive. Recent promising molecular genetic studies have,
      however, revealed the gene for infantile neuronal ceroid-lipofuscinosis, CLN1, on
      chromosome 1p32; the gene for juvenile neuronal ceroid-lipofuscinosis, CLN3, on
      chromosome 16p12.1-11.2; and the gene for a Finnish variant of late-infantile
      neuronal ceroid-lipofuscinosis, CLN5, on chromosome 13q31-32. The genes for
      classic late-infantile neuronal ceroid-lipofuscinosis, CLN2, and for adult
      neuronal ceroid-lipofuscinosis, CLN4, have not been located, the former having
      been excluded from chromosomes 1 and 16. However, the gene products of the normal
      allelic forms have not yet been identified. A considerable number of sporadic
      animal models is now available, largely equivalent to the juvenile and infantile
      forms of neuronal ceroid-lipofuscinosis, with those of the English setter and the
      South Hampshire sheep evaluated best. Recently, several mouse models have been
      added to this list of autosomal-recessive models, again the one most thoroughly
      studied being the motor-neuron disease mouse. Progress has also been made in the
      prenatal diagnosis of neuronal ceroid-lipofuscinosis: now the infantile, late
      infantile, and juvenile forms can be recognized prenatally by a combined genetic
      and electron microscopic approach.

PMID- 8576552
TI  - MRI evaluation of the brain in infantile neuronal ceroid-lipofuscinosis. Part 1:
      Postmortem MRI with histopathologic correlation.
AB  - The purpose of this study was to correlate postmortem magnetic resonance imaging
      (MRI) with histopathologic findings in brains of a series of autopsied patients
      with infantile neuronal ceroid-lipofuscinosis, a recessively inherited
      progressive encephalopathy. Eight formalin-fixed brains (age range at death, 7 to
      13 years) were examined with MRI. One patient had also undergone brain MRI 2
      years before death. Histopathologic analyses were made from standard areas
      selected on the basis of the MRI scans. Postmortem MRI findings did not differ
      significantly from the findings in the patient who was also examined during life.
      Typical findings were extreme cerebral atrophy and hypointensity of the gray
      matter structures in relation to the white matter on T2-weighted images, a
      pattern the reverse of normal. Characteristic histologic findings were almost
      complete loss of cortical neurons and secondary loss of axons and myelin sheaths
      in the white matter. The drastically altered relative intensities of the gray-
      and white-matter structures on the MRI scans reflected replacement of the neurons
      with hypertrophic astrocytes and/or macrophages filled with storage material.

PMID- 8576553
TI  - MRI evaluation of the brain in infantile neuronal ceroid-lipofuscinosis. Part 2:
      MRI findings in 21 patients.
AB  - The purpose of this study was to demonstrate the course of infantile neuronal
      ceroid-lipofuscinosis with brain magnetic resonance imaging (MRI) in children
      aged 3 months to 11 years. Twenty-one patients and 46 neurologically normal
      controls of the same age were examined. The images were evaluated visually; then
      signal intensities were measured and related to those of references. MRI
      abnormalities were detectable before clinical symptoms. The radiologic picture of
      the brain varied with the duration of the disease. Pathognomonic MRI findings in
      the early stage of the disease were generalized cerebral atrophy, strong thalamic
      hypointensity to the white matter and to the basal ganglia, and thin
      periventricular high-signal rims from 13 months onward on T2-weighted images. In
      patients over 4 years old, cerebral atrophy was extreme, and the signal intensity
      of the entire white matter was higher than that of the gray matter, which is the
      reverse of normal. This study showed that the abnormalities seen on MRI progress
      rapidly during the first 4 years of life, then stabilize, in conformity with the
      clinical and histopathologic pictures of infantile neuronal ceroid
      lipofuscinosis.

PMID- 8576554
TI  - Neurophysiologic assessment of urinary dysfunction in children with thoracic
      syringomyelia.
AB  - Isolated syringomyelia of the thoracic portion of the spinal cord is relatively
      uncommon. In children, signs and symptoms may involve only the urinary system.
      Five children who presented for evaluation of urinary tract dysfunction were
      found to have syringomyelia of the thoracic cord not associated with any other
      central nervous system abnormality on radiographic imaging. Each child underwent
      a complete neurologic examination and a complete electrophysiologic/urodynamic
      evaluation. One patient underwent surgical drainage of the syrinx due to
      progression of neurologic deficit, with slight improvement; three patients were
      treated pharmacologically to control the urinary dysfunction.

PMID- 8576555
TI  - Benign rolandic epilepsy: atypical features are very common.
AB  - The objective of this study was to determine the frequency of atypical clinical
      and electrographic features in children with benign rolandic epilepsy. A
      retrospective case series design was employed in the setting of a tertiary care
      pediatric hospital. Forty-two children with benign rolandic epilepsy were seen
      through our neurology department between January 1, 1991, and December 31, 1993.
      Their charts were reviewed for atypical clinical features, imaging studies and
      results, total number of seizures at initial presentation and last follow-up, and
      use of anticonvulsants. Atypical clinical features included status epilepticus,
      developmental delay, daytime-only seizures, screaming as a seizure component, and
      postictal Todd's paresis. All children had at least one electroencephalogram, and
      these records were reviewed for atypical electrographic features such as unusual
      location, atypical spike morphology, and abnormal background. Atypical clinical
      features were seen in 50% of patients and atypical electrographic features in
      31%. Computed tomographic scans were performed in 15 patients and were
      consistently normal. Treatment with anticonvulsant medication was initiated in
      40%. Although patients with atypical features did not have an increased seizure
      frequency, they were more likely to undergo imaging studies (P < .01) and to be
      commenced on anticonvulsant medication (P < .02). Our experience suggests that
      atypical clinical and electrographic features are the rule rather than the
      exception in benign rolandic epilepsy. Further work must be done to develop a
      reliable definition of this common entity.

PMID- 8576556
TI  - Genetic heterogeneity of hereditary motor and sensory neuropathy type VI.
AB  - Charcot-Marie-Tooth disease comprises a heterogeneous group of neurologic
      disorders that shape peripheral motor and sensory neuropathy. A classification of
      these disorders was proposed in 1975, defining seven types of hereditary motor
      and sensory neuropathy. Clinical features of hereditary motor and sensory
      neuropathy type VI are muscle weakness and atrophy in leg and hand muscles,
      leading to progressive disability and loss of vision and progressing to blindness
      due to optic atrophy. Hereditary motor and sensory neuropathy type VI was first
      reported in 1879 by Vizioli, who described a kinship in which a father and two
      sons presented with peroneal muscular atrophy in association with optic atrophy.
      Since then, at least nine similar cases have been reported: three sporadic cases,
      two pairs of siblings who were offspring of consanguineous parents, and one pair
      of siblings who were offspring of unrelated parents suggesting autosomal
      recessive inheritance. Vertical transmission has been reported only by Vizioli.
      We present a father and two offspring (one boy and one girl) with the above
      mentioned characteristic features of hereditary motor and sensory neuropathy type
      VI. Vizioli's kinship and either an autosomal recessive or autosomal dominant
      pattern of inheritance.

PMID- 8576557
TI  - Differential involvement of the brain in neonatal asphyxia: a pathogenic
      explanation.
AB  - Multiple cystic lesions in brain parenchyma supplied by the anterior cerebral
      circulation is a recognized pattern of cerebral injury associated with hypoxic
      ischemic encephalopathy in the term infant. This report presents a series of
      seven infants (gestational age, 39.3 +/- 2.8 weeks; range, 36 to 44 weeks) who
      developed multicystic encephalomalacia in the distribution of the anterior
      cerebral circulation after severe neonatal asphyxia. Cerebral imaging and
      pathologic studies demonstrate relative preservation of the cerebellum, brain
      stem, and cerebral structures supplied by the vertebrobasilar circulation.
      Compared to the vertebrobasilar vasculature, the anterior cerebral vessels in the
      term infant have dense sympathetic innervation. Asphyxia, a potent sympathetic
      stimulator, may induce vasoconstriction in the anterior circulation and
      differentially accentuate the effects of hypoxia/ischemia on cerebral tissue.

PMID- 8576558
TI  - Seizure and EEG patterns in Angelman's syndrome.
AB  - We studied the seizure and polygraphic patterns of 18 patients with Angelman's
      syndrome. All patients showed movement problems. Eleven patients were also
      reported to have long-lasting periods of jerky movements. The polygraphic
      recording showed a myoclonic status epilepticus in nine of them. Seven patients
      had partial seizures with eye deviation and vomiting, similar to those of
      childhood occipital epilepsies. These seizures and electroencephalographic
      patterns suggest that Angelman's syndrome occurs in most of the patients as a
      nonprogressive, age-dependent myoclonic encephalopathy with a prominent occipital
      involvement. These findings indicate that, whereas ataxia is a constant symptom
      in Angelman's syndrome, the occurrence of a transient myoclonic status
      epilepticus may account for the recurrence of different abnormal movements,
      namely the jerky ones.

PMID- 8576559
TI  - Demyelinating peripheral neuropathy in merosin-deficient congenital muscular
      dystrophy.
AB  - It has recently been shown that merosin, a laminin variant, is deficient in a
      proportion of patients with congenital muscular dystrophy. Merosin is a
      heterotrimer composed of the alpha 2, beta 1, and gamma 1 subunits, and further
      studies have shown that it is the alpha 2 subunit that is deficient in these
      patients. Because the alpha 2 subunit is also expressed in S-merosin, found in
      Schwann cells, we have investigated whether peripheral nerve function is also
      affected in these patients. Motor nerve conduction velocities and sensory distal
      latencies were examined in 25 cases of congenital muscular dystrophy and the
      results correlated with the merosin expression in their muscle biopsies. All but
      two of the 10 merosin-deficient cases had reduced motor nerve conduction, whereas
      all the merosin-positive cases had normal results. Analysis of the biopsies of
      these two cases showed that they produced merosin in reduced amounts, in contrast
      to all other merosin-deficient patients that produced no or only traces of
      merosin. Sensory nerve studies showed no difference between the two groups. These
      results indicate that a peripheral demyelinating neuropathy is a feature of
      merosin-deficient congenital muscular dystrophy. The fact that the alpha 2
      subunits is also expressed in Schwann cells supports the idea that the alpha 2
      gene, located on chromosome 6, is the candidate gene for merosin-deficient
      congenital muscular dystrophy.

PMID- 8576560
TI  - Brainstem multiple sclerosis in an 11-year-old child presenting as acute
      disseminated encephalomyelitis.
AB  - Multiple sclerosis and acute disseminated encephalomyelitis are demyelinating
      disorders of the central nervous system that can present initially as an acute
      focal demyelinating syndrome. We report an 11-year-old girl who initially
      presented with intractable vomiting and hypertension and later developed a
      subacute onset of focal neurologic (brainstem) signs. Magnetic resonance imaging
      (MRI) demonstrated a large solitary demyelinating lesion of the brain stem
      consistent with acute disseminated encephalomyelitis. Because of the morbidity
      associated with biopsy and its questionable value in the course of management of
      this patient, she was treated empirically with aggressive supportive measures and
      high-dose corticosteriod therapy. She had near full recovery, with only minimal
      neurologic sequelae. Six months later, she presented with similar focal
      neurologic signs, and a new lesion was found on MRI. Because of the separation of
      her two episodes in time and central nervous system location, a diagnosis of
      multiple sclerosis was made. Herein, we used this patient to illustrate the
      difficulty in distinguishing acute disseminated encephalomyelitis from multiple
      sclerosis in patients who present initially with an acute focal demyelinating
      syndrome.

PMID- 8576562
TI  - Craniocervical stenosis and apnea spells in a 2-month-old baby with
      achondroplasia.

PMID- 8576561
TI  - Acute disseminated encephalomyelitis: response to intravenous immunoglobulin.

PMID- 8576563
TI  - Critical illness polyneuropathy in a 2-year-old girl with hemorrhagic shock
      encephalopathy syndrome.

PMID- 8576564
TI  - Pineal parenchymal tumors: "oncogeny" recapitulates ontogeny.

PMID- 8576565
TI  - Carnitine in neonatal nutrition.
AB  - Experimental evidence from several investigators suggests that carnitine is a
      conditionally essential nutrient for neonates. If carnitine is a conditionally
      essential nutrient for the neonate, most neonates on total parenteral nutrition
      in the United States are not receiving adequate nutritional support. The
      metabolic functions of carnitine are varied and important in several aspects of
      neonatal physiology. All neonates receiving breast milk receive dietary carnitine
      and most neonates receiving enteral infant formulas receive dietary carnitine at
      a level similar to that of the breast-fed neonate. However, most neonates on
      total parenteral nutrition receive no dietary carnitine. Investigators have been
      testing the working hypothesis that carnitine is a conditionally essential
      nutrient for the neonate for many years. This review discusses (1) data
      supporting the hypothesis, (2) reasons why it has not been either proved or
      disproved by now, and (3) the author's view of a prudent approach to dietary
      carnitine supplementation of neonates.

PMID- 8576566
TI  - Biosynthesis and metabolism of carnitine.
AB  - This review article presents the biosynthesis, metabolism, sources, levels, and
      general functions of carnitine. Emphasis is placed on the expression of carnitine
      deficiency and insufficiency as well as the causes of these conditions. The
      various functions of carnitine are discussed as they may relate to disease
      treatment.

PMID- 8576567
TI  - Carnitine deficiency in epilepsy: Risk factors and treatment.
AB  - Numerous studies have shown that plasma carnitine levels are significantly lower
      in patients taking valproate than in controls. Free carnitine deficiency is not
      uncommon in these patients and also occurs in newborns with seizures and in
      patients taking other anticonvulsant drugs. Carnitine deficiency in epilepsy
      results from a variety of etiologic factors including underlying metabolic
      diseases, nutritional inadequacy, and specific drug effects. The relationship
      between carnitine deficiency and valproate-induced hepatotoxicity is unclear.
      Carnitine treatment does not always prevent the emergence of serious
      hepatotoxicity, but it does alleviate valproate-induced hyperammonemia. These
      studies suggest that specific risk factors for carnitine deficiency can be
      identified. Preliminary data suggest that carnitine treatment may benefit high
      risk, symptomatic patients and those with free carnitine deficiency. Carnitine
      treatment is not likely to benefit low-risk, asymptomatic patients and those with
      normal carnitine levels.

PMID- 8576568
TI  - Carnitine in human immunodeficiency virus type 1 infection/acquired immune
      deficiency syndrome.
AB  - There is an increasing body of evidence that subgroups of patients infected with
      human immunodeficiency virus type 1 possess carnitine deficiency. Secondary
      carnitine deficiencies in these individuals may result from nutritional
      deficiencies, gastrointestinal disturbances, renal losses, or shifts in metabolic
      pathways. However, tissue depletion precipitated by drug toxicities, particularly
      zidovudine, is a major etiology and concern. Carnitine deficiency may impact on
      energy and lipid metabolism, causing mitochondrial and immune dysfunction. There
      are convincing laboratory data showing the in vitro ameliorative effects of L
      carnitine supplementation of zidovudine-induced myopathies and lymphocyte
      function. Studies measuring the impact of L-carnitine supplementation on clinical
      characteristics are ongoing.

PMID- 8576569
TI  - The role of L-carnitine in pediatric cardiomyopathy.
AB  - Metabolic and genetic factors underlie some forms of cardiomyopathy in childhood.
      A variety of inborn errors of metabolism can impair mitochondrial energy
      production, or beta-oxidation, in the heart and lead to myocardial dysfunction. L
      Carnitine, an essential element of beta-oxidation, transports fatty acids across
      the mitochondrial membrane for energy production. L-Carnitine deficiency
      syndromes are now well described as secondary to a variety of inborn errors of
      metabolism and often include cardiomyopathy in the clinical picture. Despite
      traditional therapies for cardiomyopathy, mortality for this disorder remains at
      well over 50%. Review of reports of L-Carnitine supplementation studies and
      results from our own trial underscore the importance of its role in cardiac
      function and demonstrates that there is likely a subpopulation of patients with
      cardiomyopathy responsive to L-carnitine treatment.

PMID- 8576570
TI  - Primary and secondary carnitine deficiency syndromes.
AB  - The objective of this article is to review primary and secondary causes of
      carnitine deficiency, emphasizing recent advances in our knowledge of fatty acid
      oxidation. It is now understood that the cellular metabolism of fatty acids
      requires the cytosolic carnitine cycle and the mitochondrial beta-oxidation
      cycle. Carnitine is central to the translocation of the long chain acyl-CoAs
      across the inner mitochondrial membrane. The mitochondrial beta-oxidation cycle
      is composed of a newly described membrane-bound system and the classic matrix
      compartment system. Very long chain acyl-CoA dehydrogenase and the trifunctional
      enzyme complex are embedded in the inner mitochondrial membrane, and metabolize
      the long chain acyl-CoAs. The chain shortened acyl-CoAs are further degraded by
      the well-known system in the mitochondrial matrix. Numerous metabolic errors have
      been described in the two cycles of fatty acid oxidation; all are transmitted as
      autosomal recessive traits. Primary or secondary carnitine deficiency is present
      in all these clinical conditions except carnitine palmitoyltransferase type I and
      the classic adult form of carnitine palmitoyltransferase type II deficiency. The
      sole example of primary carnitine deficiency is the genetic defect involving the
      active transport across the plasmalemmal membrane. This condition responds
      dramatically to oral carnitine therapy. The secondary carnitine deficiencies
      respond less obviously to carnitine replacement. These conditions are managed by
      high carbohydrate, low fat frequent feedings, and vitamin/cofactor
      supplementation (eg, carnitine, glycine, and riboflavin). Medium chain
      triglycerides may be useful in the dietary management of patients with inborn
      errors of the cytosolic carnitine cycle or the mitochondrial membrane-bound long
      chain specific beta-oxidation system.

PMID- 8576571
TI  - Binding kinetics of an antibody against HIV p24 core protein measured with real
      time biomolecular interaction analysis suggest a slow conformational change in
      antigen p24.
AB  - The interaction between HIV core protein p24 and the murine monoclonal antibody
      CB-4/1 or its Fab fragment showed unusual kinetics. Recombinant p24 was
      immobilised in a hydrophilic carboxymethyldextran matrix. At high concentration
      of CB-4/1 Fab the association of the antigen-antibody complex proceeds in two
      phases, while dissociation is mono-exponential. The antigen has a 'memory', i.e.
      shortly after dissociation of Fab-antigen complex the fast association phase is
      enhanced. Biphasic association was also found in solution. Experiments suggest a
      reversible change of binding properties in the epitope region with an overall
      time constant of about 100 s at room temperature. Intermediate steps with faster
      time constants must be involved. Slow conformational changes of p24 seem to be
      the most probable explanation. A simple model that provides a quantitative
      description of this process could not be found. Real-time analysis of antibody
      binding by surface plasmon resonance is a powerful method for studying such
      changes in the time domain of a few seconds to a few minutes.

PMID- 8576572
TI  - Production of IL-8 and IL-4 by positively and negatively selected CD4+ and CD8+
      human T cells following a four-step cell separation method including magnetic
      cell sorting (MACS).
AB  - Highly enriched CD4+ and CD8+ human T cells were obtained from peripheral blood
      using a relatively simple and inexpensive method consisting of four steps:
      separation of mononuclear cells on Lymphoprep, removal of adherent monocytes by
      incubation in plastic petri dishes, removal of B cells, NK cells and further
      depletion of nonadherent monocytes by panning with anti-CD19, -CD16, -CD14, 
      CD11b and -CD33 mAb, and separation of CD4+ and CD8+ T lymphocytes by magnetic
      cell sorting (MACS). Cell culture for up to 48 h showed preservation of function
      by both positively and negatively selected cells as determined by production of
      IL-8. Although the cell separation procedure had no effect on interleukin-2
      receptor (IL-2R, CD25) expression, it induced production of IL-4 by both T cell
      subsets selected positively, implying cell activation by ligation of CD4 and CD8
      molecules. Irrespective of the mode of separation, CD8+ T cells produced more IL
      4, a cytokine which is associated with a Th2-type cytokine profile of CD4+ T
      cells. We conclude that our method for separating T cells into their CD4+ and
      CD8+ subsets results in high cell purities with preservation of function, as
      determined by cytokine generation. If enriched cells are to be used for
      functional studies we recommend isolation by negative selection which has less
      effect on cell function. The relevance of the finding that CD8+ T cells can be an
      important source of IL-4 remains to be elucidated.

PMID- 8576573
TI  - Enzyme-labelled antibody-avidin conjugates: new flexible and sensitive
      immunochemical reagents.
AB  - We have prepared avidin-labelled antibodies ('shuttles') with the aim of
      increasing the sensitivity of detecting mouse IgG and human complement factors in
      ELISA tests and of detecting monoclonal antibodies and digoxigenin haptens (DIG)
      in hybridization and immunoblot procedures. Avidin-D was conjugated to goat IgG
      anti-mouse IgG or to anti-digoxigenin antibodies by thiol/maleimide chemistry.
      Conjugates of different molecular weight were obtained by Superdex 200 gel
      filtration. The avidin-D-labelled antibodies were then incubated with
      biotinylated horseradish peroxidase or with biotinylated alkaline phosphatase.
      Such preformed enzyme-labelled complexes were subsequently used in the various
      assays. A 5-8-fold increase in sensitivity was found when the preformed enzyme
      labelled antibody-avidin-D complexes were compared to directly enzyme-labelled
      antibodies or antibody fragments. Furthermore it was shown that ELISA procedures
      employing digoxigenin-labelled polyclonal antibodies detected by shuttle
      conjugates were approximately five times more sensitive than biotinylated
      antibodies detected by avidin-biotin complexes (ABC method). The greatest
      sensitivity was obtained using antibody-avidin complexes which consisted of two
      IgG molecules and 4-6 avidin-D molecules.

PMID- 8576574
TI  - An antiproliferative bioassay for interleukin-4.
AB  - Interleukin-4 (IL-4) is currently being used for therapeutic intervention in a
      wide range of malignant diseases as an antitumour agent. Although bioassays have
      been developed that measure the proliferative capacity of IL-4, none measure the
      antiproliferative activity of this molecule. We have developed a simple,
      sensitive bioassay for human IL-4 based on the ability of this cytokine to
      inhibit the proliferation of the human lung carcinoma line, CCL-185, an easy to
      maintain, cytokine independent, cell line. It is rapid, reproducible and
      sensitive, able to detect 2 pg/ml IL-4. The assay is completely unresponsive to
      all other interleukins from IL-2 to IL-12, to the colony stimulating factors and
      transforming growth factor beta and is 100-fold less sensitive to interferon
      alpha, tumour necrosis factor-alpha, IL-1 beta and IL-13. The assay can be made
      completely specific for IL-4 by including specific neutralizing antibodies for IL
      4 and is suitable for the estimation of IL-4 in both plasma and serum samples.

PMID- 8576575
TI  - Detection of antigenic determinants in the Treponema pallidum membrane protein
      TmpA using overlapping synthetic peptides.
AB  - The antigenic structure of the 42 kDa membrane protein of Treponema Pallidum,
      TmpA, was studied using synthetic peptides. Ten overlapping peptides, 35-40
      residues each, were synthesized in order to cover the entire sequence of the
      molecule. The antigenic activity of the fragments was examined by enzyme-linked
      immunosorbent assay (ELISA). In this way it was possible to demonstrate a
      significant antigenic activity of four peptides which were reactive with
      syphilitic sera. The N-terminal fragment TmpA1, 38 residues long, proved to be
      the most reactive. Its antigenic structure was therefore studied in more detail,
      by examining shorter fragments. The N-terminal portion of TmpA1, consisting of 19
      residues, (ASGAKEEAEKKAAEQRALL) represents an important fragment of the molecule,
      and was specifically interactive with most of the syphilitic sera examined.

PMID- 8576576
TI  - Characterization of anti-mouse IL-12 monoclonal antibodies and measurement of
      mouse IL-12 by ELISA.
AB  - Enzyme-linked immunosorbent assays (ELISAs) capable of quantitatively measuring
      pg/ml amounts of mouse IL-12 (moIL-12) were developed as an alternative to the
      current bioassay procedure used for the measurement of moIL-12. A panel of 40 rat
      anti-moIL-12 monoclonal antibodies were identified and tested for their ability
      to bind 125I-moIL-12. Two of the MAbs, 2B5 and 9A5, were able to capture 125I
      moIL-12 in the presence of unlabelled moIL-12 p35 and moIL-12 p40, suggesting
      specificity for the moIL-12 p75 heterodimer. Western blot analysis confirmed that
      MAb 9A5 specifically recognized only moIL-12 p75. Using MAb 9A5, and an
      additional anti-moIL-12 p40 MAb 5D9, we developed quantitative ELISAs for the
      specific detection of moIL-12 p75 and p40, respectively. These ELISAs detect moIL
      12 with a sensitivity of 40 pg/ml. Whereas the p40 ELISA detected three forms of
      moIL-12 (p40 monomer, p40 homodimer, and the heterodimer), the p75 ELISA only
      detected moIL-12 heterodimer. Neither of these assays crossreacted with a panel
      of additional cytokines. The levels of moIL-12 measured by the p75 ELISA and the
      bioassay were directly compared and found to correlate well. Therefore, the p75
      ELISA represents an alternative to the bioassay for the measurement of moIL-12.

PMID- 8576577
TI  - Structural analysis of gamma delta TCR using a novel set of TCR gamma and delta
      chain-specific monoclonal antibodies generated against soluble gamma delta TCR.
      Evidence for a specific conformation adopted by the J delta 2 region and for a V
      delta 1 polymorphism.
AB  - We recently showed that secretion of non-chimeric disulfide-linked human gamma
      delta TCR ('soluble' TCR, sTCR) comprising V gamma 9 and V delta 2 regions could
      be achieved by simply introducing translational termination codons upstream from
      the sequences encoding TCR transmembrane region. Here we extended these findings
      by demonstrating efficient secretion and heterodimerization of gamma delta sTCR
      comprising V gamma 8, V delta 1 and V delta 3 regions, obtained via the same
      strategy. After immunization against immunoaffinity-purified soluble TCR, several
      hundreds of TCR-specific monoclonal antibodies (mAb) were generated, which fell
      in at least seven groups. One set of mAb was directed against a V gamma 8
      specific epitope. Strikingly, despite the high degree of sequence homology
      between V gamma 8 and other V gamma I domains, none of these mAb were
      crossreactive with other members of the V gamma I family. Three other sets of
      mAbs were shown to recognize delta chains comprising V delta 1, V delta 2 and V
      delta 3 regions respectively, regardless of their junctional sequence or of the
      gamma chain to which they were paired. Among the V delta 1-specific mAb, some
      specifically recognized V delta 1D delta J delta C delta chains while others
      reacted with both V delta 1 D delta J delta C delta and V delta 1J alpha C alpha
      chains, which suggested V domain conformational alterations induced by the C
      region. Moreover, reactivity of one V delta 1-specific mAb (#R6.11) was affected
      by a polymorphic residue located on the predicted CDR4 loop of the V delta
      region. Two delta chain-specific mAb (#178 and #515) showed a highly unusual
      reactivity, which was negatively affected by particular V delta and J delta
      sequences: (i) mAb #515 and #178 recognized all TCR delta chains except those
      comprising V delta 1 or V delta 2 regions, respectively and (ii) within TCR delta
      chains carrying 'permissive' V delta regions, none of those comprising the J
      delta 2 region were recognized by #515 and/or #178 mAbs, which suggested a highly
      specific conformation adopted by this particular J delta sequence. Apart from its
      usefulness in TCR structural studies, this novel set of mAb represents an
      important tool for the characterization and isolation of gamma delta T cells
      expressing particular combinations of V gamma/V delta regions and for analysis of
      V alpha/V delta usage by alpha beta T cells. Moreover, since our present data
      strongly suggest that gamma delta TCR are easier to obtain in a soluble form than
      alpha beta TCR, an efficient strategy for the generation of V alpha region
      specific mAb might be to immunize with chimeric gamma delta sTCR comprising
      particular V alpha regions.

PMID- 8576578
TI  - Isolation of the C9b fragment of human complement component C9 using urea in the
      absence of detergents.
AB  - The bactericidal activity of the C5b-9 complex of complement is dependent upon
      the terminal complement component C9. The precursor C5b-8 complex is not harmful
      to bacterial cells until C9 is added to complete the C5b-9 complex. The C9
      molecule can be proteolytically cleaved by thrombin to yield an intact, nicked
      molecule that remains fully functional when added to either bacterial cells or
      erythrocytes bearing pre-formed C5b-8 complexes. In investigating the
      membranolytic function of C9 in the C5b-9 complex, the carboxyl-terminal portion
      of the nicked molecule (C9b) has been shown to be membranolytic when added to
      erythrocytes, liposomes, or bacterial inner membranes in the absence of any other
      complement components. The isolation of C9b from nicked C9 has been accomplished
      by preparative gel electrophoresis using detergents, however the study of the
      activity of C9b in membrane systems may be complicated by the possible presence
      of residual detergent. To address this concern, we have used 4 M urea in
      conjunction with hydroxyapatite chromatography and a phosphate elution procedure
      to separate the domains of nicked C9. The isolated C9b domain, free of detergents
      and in the absence of any other complement components, was found to be
      membranolytic. C9b isolated in this manner was capable of lysing erythrocytes and
      inhibiting the growth of bacterial spheroplasts.

PMID- 8576579
TI  - Specificity of antibodies raised against a specific phosphoromonothioate
      oligonucleotide sequence.
AB  - The phosphoromonothioate oligonucleotide HPV (human papilloma virus) sequence
      (monothioate HPV) 5'-TTG,CTT,CCA,TCT,TCC,TCG,TC-3' was photocoupled via three
      different sites (the 5'-end, the 3'-end and the midpoint) to PPD (purified
      protein derivative) and OA (ovalbumin), and the three types of conjugates (5'
      HPV/carrier, 3'-HPV/carrier and midpoint-HPV/carrier) were used for the
      immunization of mice. Furthermore, a group of mice were immunized with the HPV
      sequence alone. No detectable antibody response against the monothioate HPV
      oligonucleotide was seen in mice receiving only the unconjugated monothioate HPV
      sequence. The OA-coupled monothioate HPV sequence also failed to elicit a
      detectable antibody response against the monothioate HPV oligonucleotide. However
      the PPD-conjugated monothioate HPV sequences induced a significant anti
      monothioate HPV antibody response in BCG (bacille Calmette Guerin)-primed mice, a
      result that must be ascribed to the effect of using PPD as a carrier in BCG
      primed mice. The antisera from all groups were tested on plates coated with the
      corresponding OA conjugates. By far the strongest response was obtained in mice
      receiving the HPV sequence coupled at the midpoint position. Further, all three
      groups of antisera obtained by immunizing with the different PPD conjugates were
      tested on microtiter plates coated with one of the three different OA conjugates.
      The antisera differed in their response depending on which OA conjugate was used
      for coating of the plate. Again, the midpoint-HPV/PPD antiserum showed the
      highest response, and this conjugate apparently represents the most efficient
      immunogen. Results from inhibition experiments with various relevant analogs of
      the monothiate HPV sequence showed that the three antiserum pools contained
      antibodies predominantly directed against the conformation of the monothioate
      backbone structure, but that at least a subpopulation of the antibodies
      recognized structures, which depended on the specific HPV base sequence.

PMID- 8576580
TI  - Hepatocyte growth factor reverses the TGF-beta-induced growth inhibition of CCL
      64 cells. A novel bioassay for HGF and implications for the TGF-beta bioassay.
AB  - The influence of human hepatocyte growth factor (HGF) on the transforming growth
      factor beta (TGF-beta) bioassay CCL-64 was examined. HGF induced proliferation of
      the CCL-64 cells and potently counteracted TGF-beta-induced growth inhibition.
      HGF was not inactivated by transient acidification to pH 2, a commonly used
      procedure to activate latent TGF-beta. HGF was a stronger mitogen for the mink
      lung cells than epidermal growth factor (EGF), a known stimulator of CCL-64 cell
      growth. Costimulation of the cells by these two cytokines resulted in an additive
      effect on proliferation. In complex biological fluids containing large amounts of
      HGF, the TGF-beta concentration can be underestimated when determined by the CCL
      64 assay. When a fixed amount of TGF-beta is added, the CCL-64 cells can be used
      as a reliable bioassay for HGF with a sensitivity of about 1 ng/ml.

PMID- 8576581
TI  - Analysis of alloreactive helper T lymphocyte precursor frequencies. Influence of
      interleukin-2 produced by the stimulating cells.
AB  - In the determination of alloreactive helper T lymphocyte precursor frequencies
      (HTLpf) by limiting dilution analysis (LDA), peripheral blood mononuclear cells
      (PBMC) are used as stimulating cells. Interleukin-2 (IL-2) production by
      stimulating T cells constitute a source of error in these assays. We found that
      100-150 Gy of gamma irradiation was required to abrogate IL-2 production by
      stimulating PBMC. This dose of irradiation, however, greatly reduced their
      allostimulatory capability. Here we describe how non-irradiated PBMC,
      immunomagnetically depleted of T cells and thus of IL-2 producing cells, can be
      used as stimulators in assays to determine alloresponsive HTLpf.

PMID- 8576582
TI  - Retrieval of human antibodies from phage-display libraries using enzymatic
      cleavage.
AB  - A combinatorial human IgG1, kappa gene library of 2 x 10(7) clones was
      constructed from a pericolic lymph node using the phagemid vector pComb3H. Fabs
      with binding activity against tetanus toxoid (TT) and keyhole limpet hemocyanin
      (KLH) were isolated from this library, and one such TT binding Fab was used to
      further evaluate a new phagemid vector for the display of recombinant antibody
      fragments (MCO1). This vector was designed to incorporate a cleavage site for the
      enzyme Genenase I, a myc peptide tag, and an amber codon between the heavy chain
      cloning site and the truncated M13 phage gene III. When MCO1 phage displaying an
      anti-TT Fab were bound to TT on a solid substrate, elution with Genenase I at
      concentrations of 5-10 micrograms/ml proved as effective as acid elution in
      releasing bound phage. Furthermore, enzymatic elution with Genenase I was
      comparable to acid elution in the enrichment of a TT binding Fab from the
      pericolic library subcloned into the vector MCO1. Importantly, the use of
      enzymatic or acid elutions resulted in the retrieval of different anti-TT Fabs
      from this same library. We conclude that panning of phage-displayed combinatorial
      antibody libraries can be successfully performed using enzymatic elution, and
      that this offers a useful alternative to currently available phage elution
      techniques.

PMID- 8576583
TI  - Influence of fluorescent antibody probe specificity on flow cytometric analysis
      of antibody-producing cells.
AB  - In the flow cytometric analysis of the stability of antibody-producing cells,
      fluorescent antibody probes specific for immunoglobulin heavy chains have been
      widely utilized to quantify intracellular antibodies. To investigate the effect
      of the specificity of antibody probes on flow cytometric analysis, non-producing
      subclones of the 6-31 transfectoma were stained with fluorescein isothiocyanate
      (FITC)-conjugated anti-human IgGs specific for heavy chain and light chain,
      respectively. The use of heavy chain-specific probe identified heavy chain-only
      producers as producers, whereas the use of light chain-specific probe identified
      light chain-only producers as producers. Thus, both heavy chain-specific and
      light chain-specific antibody probes should be used for the accurate evaluation
      of heterogeneous non-producing population. Furthermore, the results of the flow
      cytometric analysis were confirmed by immunoblotting, suggesting that flow
      cytometry is a useful technique for the rapid evaluation of the stability of
      transfectomas producing chimeric antibody.

PMID- 8576586
TI  - Has medicine lost its heart?

PMID- 8576584
TI  - Biotinylation of cell surface MHC molecules: a complementary tool for the study
      of MHC class II polymorphism in cattle.
AB  - Biotinylation of cell surface proteins is often used as an alternative to
      radioactive labelling procedures, but very little is known about the labelling of
      the different allelic products of polymorphic antigenic systems. In this report,
      we demonstrate that NHS-LC-biotin labels bovine MHC class II molecules with
      different efficiencies for several allelic forms of this polymorphic system
      compared to conventional metabolic labelling with [35S]methionine. This was shown
      after immunoprecipitation and one-dimensional isoelectric focusing (1D-IEF). The
      avidity of the monoclonal antibody Bo139 (alpha-bovine MHC class II) was not
      affected after in situ biotinylated of bovine PBMC, as revealed by flow
      cytometric analyses, immunoblotting after SDS-PAGE and immunoprecipitation. The
      biotinylation did not affect the apparent isoelectric points of polymorphic
      bovine MHC class II beta chains. This was demonstrated by double labelling of
      cells with [35S]methionine and subsequent biotinylation and comparison of the
      banding pattern after immunoprecipitation and 1D-IEF. 1D-IEF of 11 unrelated
      animals resulted in the demonstration of 29 polymorphic bands of which eight were
      detected by both labelling procedures, six only after biotinylation and 15 only
      after metabolic labelling with [35S]methionine. Hence, biotinylation alone cannot
      serve as an alternative for radioactive labelling of bovine MHC class II
      molecules but can reveal expressed allelic forms not detectable by metabolic
      labelling with [35S]methionine.

PMID- 8576585
TI  - Use of immobilized adenosine deaminase (EC 3.5.4.4) for the rapid purification of
      native human CD26/dipeptidyl peptidase IV (EC 3.4.14.5).
AB  - The leukocyte differentiation antigen CD26 identified as dipeptidyl peptidase
      IV.(EC 3.4.14.5), cleaves off N-terminal dipeptides from peptides when a proline
      or alanine is located at the penultimate position. Seminal plasma and especially
      prostasomes, prostate-derived organelles which occur freely in seminal plasma,
      contain high amounts of CD26/dipeptidyl peptidase IV and therefore are suitable
      sources for the purification of the protein. The use of adenosine deaminase (EC
      3.5.4.4) affinity chromatography for its purification is described.
      CD26/dipeptidyl peptidase IV was purified from human seminal plasma and
      prostasomes by a two step procedure. Ion exchange chromatography on DEAE
      Sepharose, followed by affinity chromatography on adenosine deaminase-Sepharose
      resulted in the pure, native protein with an overall yield ranging from 35 to
      55%. The N-terminal sequence of the amphiphilic enzyme purified from human
      prostasomes was determined to be Met-Lys-Thr-Pro-Trp-Lys-Val-Leu. The preparation
      obtained was free of contaminating aminopeptidase activity and proved to be very
      stable (up to 1 month at 37 degrees C). The calf intestinal adenosine deaminase
      we used is commercially available and can be employed for the purification of
      human, bovine and rabbit CD26/dipeptidyl peptidase IV. High affinity binding of
      porcine dipeptidyl peptidase IV was not observed. The availability of a source
      with high specific activity and the introduction of adenosine deaminase affinity
      chromatography permits the rapid purification of milligram quantities of natural
      mammalian CD26/dipeptidyl peptidase IV.

PMID- 8576588
TI  - Fine needle aspiration cytology of bone and joint lesions: an assessment.
AB  - Fine needle aspiration cytology and subsequent correlation with histology and
      therapeutic follow-up was done in 198 cases of bone and joint lesions. Overall
      accuracy was found to be 87.34%; false diagnosis was recorded in 4.5% of cases;
      8.08% cases were excluded from correlation as they did not turn up for further
      treatment or follow-up after the diagnosis. False diagnosis was encountered
      mostly with inflammatory lesions and primary neoplasms, diagnosing osteosarcoma
      and Ewing's sarcoma as chronic inflammatory lesion, chondroma as chondrosarcoma
      and vice versa. The possible cause of default has been discussed. The benign
      cystic lesions could be diagnosed with almost 100% accuracy by fine needle
      aspiration cytology where 10% cases were excluded as they could not be followed
      up.

PMID- 8576587
TI  - Posterior fossa extradural haematoma.
AB  - Seventeen patients with posterior fossa extradural haematoma are presented. While
      7 patients had acute course, 6 had subacute and 4 had chronic course. All
      patients had evidence of occipital injury. Two patients did not have any fracture
      in the occipital bone. Concomitant lesions included cerebellar contusion in 3
      cases, cerebral contusion in 4 patients, supratentorial extradural haematoma in 2
      and hydrocephalus in 2 patients. All but one patient were treated surgically.
      None of the supratentorial lesions were operated upon. All patients with subacute
      and chronic course had good outcome while 43% with acute course succumbed to
      death. Besides the initial clinical status the co-existing lesions signifying the
      increased severity of injury have influenced the mortality and quality of
      outcome. In presence of occipital fracture a careful observation and timely
      intervention are warranted.

PMID- 8576589
TI  - The relationship of sonographic placental grading, biochemical pulmonary maturity
      and neonatal outcome in pregnancy-induced hypertension.
AB  - In a prospective study, the accuracy of placental grade in predicting pulmonary
      maturity was evaluated in 50 cases of pregnancy-induced hypertension (PIH)
      between 28 and 41 weeks of gestation. Pulmonary maturity was measured by
      lecithin/sphingomyelin (L/S) ratio and phosphatidylglycerol (PG) in amniotic
      fluid and by clinical development of respiratory distress syndrome (RDS) in the
      neonates. Fifty normotensive healthy primigravidae, who were matched for age and
      period of gestation, served as control. No difference (p > 0.05) in the placental
      grading was observed between normotensive and hypertensive pregnancies. The
      advancement of placental grade was found to be associated with an increase in L/S
      ratio and PG level in amniotic fluid. A mature placental grade (grade III)
      identified by real-time sonography corresponded to foetal lung maturity (L/S > or
      = 2.0, PG > or = 0.36 mg/dl) and absence of RDS in all cases. Hence, in PIH a
      grade III placenta appeared to be a reliable predictor of foetal lung maturity in
      the population examined.

PMID- 8576591
TI  - Estimation of chronic disease load in a rural area of Haryana.
AB  - A key informant based survey was done in 1992 to enlist cases of chronic
      disorders in a rural area of Haryana. Thirty-nine villages selected purposely
      from a block were surveyed by a trained field worker. He made contacts with key
      informants like dais, anganwadi workers, health workers, teachers, village
      elders, etc, to enlist known cases of chronic disorders. In all 812 cases of
      chronic disease were encountered in 28844 population (28.2/1000). Prevalence of
      chronic disorders was more in higher age group. Males outnumbered females in
      younger age group and vice versa for higher age group. Asthma, poliomyelitis,
      mental illness/retardation were more prevalent in males while hypertension,
      obesity were reported more in females. Tuberculosis, diabetes, hypertension and
      asthma were significantly more prevalent in higher age group while poliomyelitis
      was reported more in children. Consultation rate was high in tuberculosis,
      asthma, hypertension and diabetes.

PMID- 8576590
TI  - Immunological parameters in leprosy patients with and without arthritis.
AB  - Twelve patients of leprosy with arthritis and 161 patients without arthritis were
      studied for immunological parameters like immunoglobulins (IgG, IgM, IgA), C
      reactive proteins and rheumatoid factor. There was increase in the levels of IgG,
      IgA value in leprosy patients with and without arthritis compared to healthy
      control. IgM level was decreased in both the groups compared to control, but
      significant decrease was observed (p < .01) in patients with arthritis. C
      reactive protein was significantly positive in leprosy with arthritis group (p <
      .01) and positive in 12 cases of leprosy without arthritis group compared to
      negative control group. Rheumatoid factor was present in leprosy with arthritis
      (16.6%) compared to both the control group and leprosy without arthritis group.
      This study concluded the presence of arthritis in leprosy patients as a definite
      entity which showed changes in immunological parameters.

PMID- 8576592
TI  - Host factors and pneumonia in hospitalised children.
AB  - Acute respiratory infections (ARI) account for 20-24% of childhood deaths in
      India. The present study investigated the host related risk factors in the
      outcome of pneumonia in 127 hospitalised children between the ages of 2 months
      and 5 years. The case fatality rate in the study was 11.8%. Presence of
      malnutrition is a significantly important factor for both increased duration of
      pneumonia and fatal outcome. Other factors for increased pneumonia mortality
      include the presence of associated illness and the severity of the pneumonia.

PMID- 8576593
TI  - Epilepsy surgery in India.

PMID- 8576594
TI  - Early splenic metastasis in a case of renal adenocarcinoma.

PMID- 8576595
TI  - Stroke in a young patient with mitral valve prolapse.

PMID- 8576596
TI  - Mesenteric fibromatosis.

PMID- 8576597
TI  - Postoperative lumbar pseudomeningocele.

PMID- 8576598
TI  - Chondromyxoid fibroma: a report of two cases.

PMID- 8576599
TI  - Residency programme in cardiothoracic surgery: problems and solutions.

PMID- 8576600
TI  - Atypical postponing of fever in a case of vivax malaria.

PMID- 8576601
TI  - Identification of medicine.

PMID- 8576603
TI  - Damaged cells rehabilitated with Swedish light treatment.

PMID- 8576602
TI  - Old wine in a new bottle.

PMID- 8576604
TI  - Incidence of "chance" smear positivity among MB leprosy patients after MDT.
AB  - Multidrug therapy (MDT) was introduced in 1982. Nine hundred eighty
      multibacillary (MB) leprosy patients had successfully completed the MDT
      administered for a minimum of two years or till skin smear negativity, whichever
      was later, as recommended by the World Health Organisation (WHO). During
      surveillance, 2.24% of them revealed presence of acid-fast bacilli (AFB) in the
      skin smear. They did not have any clinical evidence suggestive of relapse.
      Subsequent followup (without antileprosy chemotherapy) for periods ranging from
      one to eight years was uneventful. We have called this as "chance smear
      positivity" where a few bacilli, yet to be cleared by the immune system, were
      picked up by routine skin smear examination.

PMID- 8576605
TI  - Impact of knowledge of leprosy on the attitude towards leprosy patients: a
      community study.
AB  - NLEP, through its survey-education-treatment (SET) pattern, attempts to educate
      the community members about the scientific facts of leprosy with the view to
      improve their knowledge leading to a more positive attitude towards the leprosy
      afflicted. This paper explores the impact of knowledge on the attitudes of 1199
      community members drawn from two States, Andhra Pradesh and Orissa, towards
      leprosy. The results show that, overall, a high knowledge level did not
      necessarily generate positive attitudes. There was a general negative attitude
      despite 35% to 50% of the respondents having high knowledge level. There were,
      however, situations in which a high level of knowledge helps to have positive
      attitudes. These situations differ in the two states studied.

PMID- 8576606
TI  - Intracellular localization of dapsone and rifampicin in skin and nerve of
      multidrug treated leprosy patients.
AB  - Intracellular localization of antileprosy drugs dapsone (DDS) and rifampicin
      (RFP) was carried out on skin and nerve lesions obtained from multidrug treated,
      multi (BL-LL)- and pauci (BT-TT) bacillary cases of leprosy using
      immunocytochemical techniques. Intracellular localization of the above drugs
      especially in macrophages and Schwann cells was aimed by using rabbit raised anti
      DDS and RFP polyclonal antibody in an indirect peroxidase assay. Our study
      records both intra and extracellular staining with anti DDS and RFP antibodies in
      the skin as well as nerve lesions of MB and PB cases treated with MDT. All the
      nerves under investigation had moderate to severe pathology and hence free
      diffusion of the drug could be attributed to the broken barrier. Basal lamina
      around the Schwann cell did not seem to form a barrier. It was also noted that
      the drug (metabolite) persisted over a long period of time).

PMID- 8576607
TI  - Prospects for elimination of leprosy in India by 2000 AD.
AB  - Data regarding the trends of new-case detection rates of leprosy for India as a
      whole, for the State of Andhra Pradesh, and for Srikakulam district in Andhra
      Pradesh were generated and projected up to 2000 AD. The prevalence rate by 2000
      AD was worked out based on these new -case detection rates. The projections show
      that at the current slowly declining trend of new-case detection, with 20% MB
      cases among the newly detected cases and the current mean duration of treatment,
      the elimination goal of leprosy by 2000 AD, could possibly be achieved at
      Srikakulam district level only, where the MDT project has been under
      implementation for over ten years, but not at the State or country levels. The
      achievement of elimination goal should be possible in other geographic units also
      if the duration of disease could be shortened to one month or less, for both
      paucibacillary and multibacillary types of leprosy.

PMID- 8576608
TI  - Role of antineural antibodies in perpetuation of a pre-existing peripheral nerve
      damage in leprosy.
AB  - This study was carried out in order to find out whether antineural antibodies had
      a role to play in perpetuating pre-existing nerve damage in leprosy. Indirect
      ELISA was carried out on sera from 20 leprosy patients and five normal controls
      using antigen prepared from peripheral nerves of a cured bacteriologically
      negative leprosy patient. None of the patients had significant levels of IgG
      antibodies whereas eight of them (40%) had significant levels of IgM antibodies.
      However, there was no correlation with duration of disease, treatment received,
      nerve enlargement or active neuritis. The nature of these antibodies is
      discussed.

PMID- 8576609
TI  - Bacterial clearance with WHO--recommended multidrug regimen for multibacillary
      leprosy.
AB  - Sixty multibacillary leprosy patients with an average initial bacteriological
      index (BI) of 2.5 were followed up after they had completed the WHO--recommended
      multidrug therapy regularly till attaining bacteriological negativity. The
      minimum duration of treatment was two years as stipulated by WHO and the maximum
      duration for reaching negativity was seven years (mean 4.25 years). The minimum
      time for the attainment of bacteriological negativity was one year and the
      maximum was 6.75 years (mean 3.75 years). The higher the initial BI the longer
      was the time taken for the attainment of bacteriological negativity. The average
      fall of BI per year was 0.67. Dapsone monotherapy received before the
      commencement of MDT, prednisolone received during therapy and the type of leprosy
      did not have any effect on the time taken for bacteriological clearance. There
      was no relapse during the period of observation (mean 2.83 years). The site to
      attain negativity last was the ear lobe, in 95% of the cases.

PMID- 8576610
TI  - Studies on microbial aerobic flora of skin in leprosy patients.
AB  - This study reports the isolation and identification of aerobic organisms from
      biopsies/slit-skin smears/scrapings from 129 leprosy patients and 50 healthy
      controls. These include 56 paucibacillary (PB) and 73 multibacillary (MB) cases.
      Thirty-six isolates from the specimens from 21 patients and 15 healthy controls
      were grown. The non-mycobacterial isolates from clinically PB leprosy (TT/BT/I)
      patients were: (1) Gram-positive cocci: Staphylococcus aureus(1), Staphylococcus
      albus(1); (b) Gram-positive bacilli: Bacillus subtilis(1), Corynebacterium
      xerosis(1); (c) Gram-negative bacilli: Escherichia coli(1), Proteus mirabilis(2),
      Klebsiella pneumoniae(1) and Pseudomonas aeruginosa(1). The isolates from
      clinically MB leprosy (BB/BL/LL) patients were: (a) Gram-positive cocci:
      Micrococci(1), Staphylococcus aureus(1) and Staphylococcus albus(1); (b) Gram
      positive bacilli: Corynebacterium xerosis(1); Corynebacterium hofmanni(1) and
      Bacillus cereus(1). (c) Gram-negative bacilli: Escherichia coli(2), Klebsiella
      pneumoniae(1) and Proteus mirabilis(2). The specimens from healthy controls
      yielded similar organisms. These were (a) Gram-positive cocci: Staphylococcus
      albus(2), Staphylococcus aureus(2) and Micrococci(2); (b) Gram-positive bacilli:
      Corynebacterium xerosis(1), Bacillus subtilis(2), Corynebacterium hofmanni(1) and
      Bacillus cereus(1); (c) Gram-negative bacilli: Escherichia coli(3), Proteus
      vulgaris(1) and Proteus mirabilis(1). While these results show no significant
      differences in the species types of non-mycobacterial aerobic organisms isolated
      from healthy skin and PB/MB types of leprosy, these isolates need to be
      characterized by immunological/molecular methods to find out subtypes if any.

PMID- 8576611
TI  - Isolation and characterization of cultivable mycobacteria from leprosy skin.
AB  - Attempts were made to isolate cultivable mycobacteria from 129 biopsies/slit-skin
      scrapings from the skin of leprosy patients (73 multibacillary-BB/BL/LL and 56
      paucibacillary-TT/BT/I) as well as 50 healthy controls. Among the 19 isolates
      obtained, 17 were from specimens from leprosy cases whereas two were from healthy
      controls. 14 of the 17 isolates were from multibacillary cases and three were
      from paucibacillary patients. The mycobacteria isolated were: M.scrofulaceum (4 =
      all LL cases); M.avium (3 = 2 from LL cases and 1 from healthy control); M.avium
      intracellulare complex (1 LL); M.gordonae (2 = 1 from BT and BB each);
      M.flavescens (1 BL); M.smegmatis (2 = both LL); M.phlei (4 = 1 LL, 1 BL, 1 BT and
      1 healthy control); M.fortuitum (1 BL); and M.chelonei (1 BT relapse). The
      results of this study suggest a preferential colonization of skin of lepromatous
      leprosy cases by M.scrofulaceum and M.avium. As such isolates have been reported
      by the investigators from other parts of the world, independent confirmation of
      such trends in Indian patients is significant and casual relationship (if any)
      between such colonization and development of lepromatous disease merits further
      investigation.

PMID- 8576612
TI  - Women workers in leprosy.

PMID- 8576613
TI  - Relapse in leprosy.

PMID- 8576614
TI  - Relapse after MDT in MB cases.

PMID- 8576615
TI  - WHO Chemotherapy Study Group 1993.

PMID- 8576616
TI  - [The influence of pregnancy and delivery on the climacteric symptoms].
AB  - This study was undertaken to investigate the influence of past pregnancy and
      delivery on the perimenopausal status in 144 women (48-52 years of age).
      Individual interviews to ascertain the personal profile, medical history, events
      at pregnancy, delivery and puerperium, and the kind and severity of climacteric
      symptoms were held. The subjects were divided into two groups by means of a
      simplified menopausal index (SMI): group A had climacteric symptoms (SMI > 50)
      and those in group B had mild symptoms (SMI < or = 50). The analysis of the
      principal components, and the correlation among the variables revealed that three
      factors--the impression and events at past pregnancies and deliveries,
      reproductive functions, and the psycho-character properties--had a significant
      influence on the status at the perimenopause, but the social-environmental
      factors appeared to have no significant influence on the severity of climacteric
      symptoms.

PMID- 8576617
TI  - [Isolation and purification of pregnancy-associated plasma protein A].
AB  - We tried to purify pregnancy-associated plasma protein A (PAPP-A) from normal
      term maternal serum in this study by means of a three step chromatographic
      procedure. At first 30 ml of maternal serum samples were applied to a column for
      sieve chromatography and eluted according to molecular weight. PAPP-A was
      detected in the high molecular weight fraction area by radioimmunoassay for PAPP
      A, and 91% of the total amount of PAPP-A in the maternal samples was recovered.
      Secondary PAPP-A containing fractions were applied to a Heparin-Sepharose column
      and eluted by a stepwise increase in NaCl 0.15, 0.30 and 0.60 M in 0.05 M Tris
      HCl buffer, pH 7.8. Ninety-three percent of PAPP-A in applied samples was
      recovered under the 0.6 M NaCl condition. Thirdly the pooled fractions which
      contained PAPP-A after Heparin-Sepharose affinity chromatography were applied to
      DEAE-Sephacel Chromatography and eluted by a stepwise increase in NaCl 0.15, 0.30
      and 0.45 M in 0.01 M acetate buffer, pH 5.5. Ninety-one percent of PAPP-A in
      applied samples was recovered under the 0.3 M NaCl condition. Finally PAPP-A
      containing fractions were concentrated 10 times and 3.8 IU (1.7 mg) of PAPP-A was
      isolated. The purification schedule removed approximately 99% of total protein in
      the maternal serum while 74% of PAPP-A was recovered. The purification factor
      (fold), which was calculated as the increase in specific activity (mIU:PAPP
      A/mg:protein) in comparison with the starting value in the maternal serum, was
      526. And the purity (mg:PAPP-A/mg:protein) of the final product was 68.4%.
      Analysis of the final purified material by SDS-PAGE showed a single band of
      200kDa, and western blot analysis showed that the main purified protein was PAPP
      A. The immunological identity of the PAPP-A purified in this study to the PAPP-A
      donated by Teisner et al., was recognized by crossed immunoelectrophoresis and
      tandem crossed immunoelectrophoresis. We hope that the new PAPP-A purified in
      this study can be utilized for the development of a sensitive and convenient
      assay for PAPP-A and its standard material, and also for basic study to clarify
      the biological function of PAPP-A in the human body.

PMID- 8576618
TI  - [Assessment of degree of edema by means of bioelectrical impedance during
      pregnancy].
AB  - It is well known that the total body water in women with toxemia of pregnancy
      expands beyond the normally increased volume that characterizes pregnancy.
      Although abnormally increased water retention is usually diagnosed by both the
      edema of the legs and the weight gain, these methods are not quantitative. To
      quantify the degree of edema, we used bioelectrical impedance analysis (BIA).
      Because water and electrolytes are the dominant factors affecting electrical
      conduction in the body, the increase in total body water (the degree of edema) is
      assessed by BIA. BIA was conducted serially in a group of 38 normal pregnant
      women during pregnancy and 4 pregnant women with toxemia of pregnancy. The values
      for bioelectrical impedance in normal pregnant women decreased gradually during
      pregnancy, suggesting a physiological increase in total body water (p < 0.01). In
      contrast, the values for bioelectrical impedance dramatically decreased in the
      cases of 4 women with toxemia of pregnancy and accurately increased in the
      process of recovery from toxemia of pregnancy. These findings indicate that
      bioelectrical impedance analysis is a useful and practical method for assessing
      the increase in total body water.

PMID- 8576619
TI  - [A study on the association between glandular dysplasia and cervical squamous
      neoplasia in surgical specimens].
AB  - To clarify the pathogenesis of cervical adenocarcinoma, we studied the biological
      properties of glandular dysplasia (GD). The coexistence of squamous neoplasia
      with cervical adenocarcinoma has been demonstrated. We analyzed the incidence of
      the coexistence of GD with squamous neoplasia in this study. Materials were
      surgically removed uterine cervix specimens (n = 142), 52 benign disease cases,
      19 squamous dysplasias of the uterine cervix, 66 squamous cell carcinomas of the
      uterine cervix and 5 cervical adenocarcinomas. Diagnosis of GD was based on the
      general rules for clinical and pathological management of uterine cervical cancer
      and Ng's criteria (1983). We divided GD into two types: I: endocervical type, and
      II: endometrioid type. These fell into subtypes, a (mild) and b (severe) based on
      the observed degrees of cell atypia. 1. GD coexisted in 17.3% of benign disease
      cases, 15.8% of squamous dysplasias, 24.2% of squamous cell carcinomas and 100%
      of cervical adenocarcinomas. 2. GD Ib and IIb were not found in any of the benign
      disease cases, but were present in 15.8% of squamous dysplasias, 13.6% of
      squamous cell carcinomas and 100% of cervical adenocarcinomas. If GD was defined
      as only Ib and IIb, GD coexisted with squamous neoplasia in this study. Our
      results support the theory that both cervical squamous atypia and cervical
      glandular atypia are derived from reserve cells.

PMID- 8576620
TI  - [Clinical significance of magnetic resonance imaging (MRI) in evaluation of
      radiotherapeutic effect on uterine cervical cancer].
AB  - Serial magnetic resonance imaging (MRI) studies were performed in 27 patients
      undergoing primary radiation therapy for invasive cervical carcinoma, to assess
      the efficacy of this therapy. MRI findings included a high intensity area (HIA)
      in the uterine cervix and five parameters indicative of extrauterine spreading of
      the carcinoma: vaginal invasion, parametrial invasion, vesical invasion, rectal
      invasion and lymph node enlargement. In 26 of the 27 (96%) cases, the HIA was
      found prior to treatment, and remained in 17 (63%) cases at the end of the
      treatment. But in 10 of the patients with a residual HIA, this region resolved 3
      to 8 months after treatment, and these patients had no evidence of residual tumor
      in the cervix on pathologic examination. The accuracy was lower in MRI
      examinations performed less than 6 months after the treatment (49%) than in
      examinations performed more than 7 months after the treatment (93%), suggesting
      that the HIA in the early post-treatment phase may be related to inflammatory
      changes. Findings indicative of extrauterine spreading decreased following
      treatment, but patients with recurrence had higher scores than those with no
      evidence of recurrence completion of the primary therapy. Furthermore, in 2
      patients with local recurrence more than 1 year after treatment, the abnormal MRI
      findings reappeared and increased after the initial resolution of these findings
      with treatment. The present results indicate that MRI is clinically effective in
      evaluating the effects of radiotherapy in patients with cervical cancer.

PMID- 8576621
TI  - [Adjuvant chemotherapy with cyclophosphamide, adriamycin, and CDDP (CAP) for high
      risk endometrial cancer after complete surgery].
AB  - One hundred and six patients with endometrial cancer were treated at Tsukuba
      University Hospital between 1983 and 1992. Sixteen patients who underwent
      complete resection were at high risk for recurrence and were given adjuvant
      platinum-based, multiagent chemotherapy instead of adjuvant radiotherapy.
      Eligibility criteria included outer-third myometrial invasion (group 1; n = 5),
      pelvic lymph node metastasis (group 2; n = 3) or both myometrial invasion and
      lymph node metastasis (group 3; n = 8). Of these three groups at high risk for
      recurrence, each patient in groups 1 and 2 developed recurrence and died. In
      group 3 two patients developed recurrence and one patient has died. There was one
      treatment death due to neutropenic sepsis in group 3. The recurrence sites in all
      four patients were local and no distant recurrence was noted. In other words, of
      15 patients (excluding one treatment death) at high risk for recurrence, three of
      12 patients (25%) with deep myometrial invasion and three of 10 patients (30%)
      with positive pelvic lymph nodes developed recurrence and died. The other 12
      patients (include one patient with recurrence; 100 months) have survived for a
      long interval (range, 45-131 months). The survival rates for stage I, II, III,
      and IV are 92.6, 89.5, 60.0%, respectively. Patients with stage I in this study
      had a better survival than those with stage I in the 1984 annual report of the
      Japan Society of Obstetrics and Gynecology (p < 0.05). The findings of this
      prospective clinical trial supported those of the randomized trial comparing
      adjuvant CAP with radiation therapy.

PMID- 8576622
TI  - [Usefulness of newly developed subcutaneous one point lifting method in
      gynecological laparoscopic operation].
AB  - We first introduced the abdominal wall lifting method in gynecological
      laparoscopic operations in 1994. Now we have developed a new one-point lifting
      technique (Tokyo Medical College method) that enables gynecological laparoscopic
      operations to be performed more safely, easily and economically. 1. The TMC
      method provides a sufficiently spacious operative field in the same way as
      artificial pneumoperitoneum and can overcome the negative influence of obesity on
      the operative field. 2. Because the abdominal wall is lifted up by means of a
      single stainless steel wire passed under the skin in this method, the limitations
      of previous methods are completely overcome. Furthermore setting up for this
      method is very easy and can be completed in a short time. 3. Because the aperture
      for the Surgigrip made in the abdominal wall is short and has a large internal
      diameter, we can manipulate operative instruments freely. Especially suturing and
      ligation can be carried out simply and accurately. 4. We were able to continue
      irrigation and suction without deterioration of the operative field and to easily
      remove resected tissue from the abdominal cavity. 5. The frequency of
      intracorporeal suture and ligation in this method increased significantly
      compared with the pneumoperitoneum method in cases of ovarian diseases. As a
      result, most operative procedures in ovarian diseases became cystectomies,
      preserving the healthy part of the ovary. This also reduced operative cost by
      avoiding expensive autosuture equipment. 6. There were no complications such as
      subcutaneous bleeding with this method. There was no significant difference
      between this method and pneumoperitoneum in terms of postoperative pain. The TMC
      method is a new laparoscopic operative technique that allows procedures to be
      performed under conditions close to laparotomy procedures and solves most of the
      problems of the pneumoperitoneum method.

PMID- 8576623
TI  - [Histopathological findings of malacoplakia of the adnexa uteri].

PMID- 8576624
TI  - [Prenatal diagnosis of Hunter syndrome in a carrier and her twin sisters].

PMID- 8576625
TI  - [Clinical study on six cases of immature ovarian teratoma with special reference
      to the preservation of fertility].

PMID- 8576626
TI  - [The management of pregnancy with hereditary spherocytosis].

PMID- 8576627
TI  - [Comparison of fetal circulatory responses during maternal bleeding and fetal
      bleeding].
AB  - The purpose of this study was to compare the fetal circulatory responses during
      maternal hemorrhage and fetal hemorrhage. Four pregnant goats, gestational age
      131 +/- 7 days for the fetal hemorrhage and 5 goats, 132 +/- 2 days (term 145
      days) for the maternal hemorrhage were used. The amounts of hemorrhage were 700ml
      per 2 hours for the maternal hemorrhage and 40ml per 2 hours for the fetal
      hemorrhage. Although fetal arterial pH decreased during both hemorrhages, fetal
      arterial pO2 increased during the fetal hemorrhage and decreased in the maternal
      hemorrhage. The fetal arginine vasopressin concentration and plasma renin
      activity increased during both hemorrhages, but the rates of change in the
      hormone concentrations were higher during the fetal hemorrhage. The fetal
      aldosterone concentration decreased during maternal hemorrhage but increased
      during fetal hemorrhage. FAP increased and FHR decreased during maternal
      hemorrhage. FAP and FHR were significantly correlated to the AVP concentration.
      These relationships were not found during fetal hemorrhage. We therefore
      concluded that fetal responses were completely different in pO2, FAP and FHR
      during the maternal and fetal hemorrhages.

PMID- 8576628
TI  - Problems and pitfalls in providing acute and short-term pain relief with
      nonsteroidal anti-inflammatory agents.
AB  - NSAIDs are extremely versatile and effective analgesics and anti-inflammatory
      agents that are generally very safe to use in young, healthy adults. However,
      physicians should be aware of those patients who are at greater risk of toxicity
      from their use and avoid or modify NSAID treatment in these individuals. Certain
      newer NSAIDs seem to offer lower gastric or renal toxicity and might be
      preferable in high-risk patients.

PMID- 8576629
TI  - The Journal 150 & 100 years ago. January 1846 and 1896.

PMID- 8576630
TI  - Percutaneous treatment of aortoiliac atherosclerosis: a case report.
AB  - This case report describes the current usage of percutaneous techniques in the
      treatment of aortoiliac atherosclerotic disease. The kissing balloon technique
      was utilized to perform percutaneous transluminal angioplasty of the distal aorta
      and its bifurcation. Subsequently, bilateral vascular stents were placed
      extending from the common iliac arteries into the aorta. Following stenting and
      percutaneous transluminal angioplasty, angiography demonstrated excellent blood
      flow in the aorta and iliac vessels. Palpable distal pulses were restored, and
      the patient's symptoms were alleviated. Percutaneous revascularization techniques
      offer an alternative to surgery in the treatment of selected patients with
      stenotic aortoiliac disease.

PMID- 8576631
TI  - ECG of the month. Electrical bridges. Ventricular preexcitation.

PMID- 8576632
TI  - Evaluation of relatives for congenital heart defects.
AB  - Current and developing knowledge of mechanisms underlying the embryological
      development of congenital heart defects strongly suggests that medical evaluation
      should be extended to relatives of patients. Relatives may be found to have
      either subclinical or significant heart defects of specific forms that are
      phylogenetically related to the disorder of the index case. Discovery of the
      disorder in relatives allows better medical management and lends accuracy to
      assessment of the risk of congenital heart defects in future progeny of
      relatives.

PMID- 8576633
TI  - Motion sickness.
AB  - Motion sickness is a common phenomenon affecting most patients at some point in
      life. Car sickness, airsickness, seasickness, and space sickness all involve a
      neural mismatch or confusion between the vestibular, visual, and proprioceptive
      systems that produces the symptoms of motion sickness. Therapy is directed toward
      decreasing conflicting sensory input, controlling nausea, and speeding the
      process of adaptation.

PMID- 8576634
TI  - Ethanol modulates apolipoprotein B mRNA editing in the rat.
AB  - We have studied the rat ethanol-liquid diet model for chronic ethanol modulation
      of lipid homeostasis, apolipoprotein (apo) B production and apoB mRNA editing.
      Male Wistar rats were fed one of three diets: i) regular chow, ii) an isocaloric
      liquid diet, or iii) isocaloric ethanol-liquid diet where ethanol accounts for
      35.5% of the total calories, for up to 40 days. There was no difference in body
      weight or liver/body weight ratio among the three groups of animals at the end of
      the feeding period. Hepatic and plasma triglycerides were elevated in the ethanol
      treated animals only, correlated with an accumulation of lipid particles in the
      liver of these animals. By DNA excess hybridization, the steady state mRNA levels
      of apoB and apoB mRNA-editing protein relative to actin were not significantly
      altered. The proportion of edited apoB mRNA; i.e., apoB-48 mRNA/(apoB-48 + B-100)
      mRNA, increased in a time-dependent manner from approximately 50% to 100% in the
      ethanol-treated group. It remained unchanged in the chow- and liquid diet-fed
      animals. The proportion of apoB-48/apoB-100 protein synthesis was determined by
      [35S]methionine labeling followed by specific immunoprecipitation and SDS
      polyacrylamide gel electrophoresis. The amount of newly synthesized apoB-48
      increased from 30-50% to > 99% of the total apoB (apoB-48 + apoB-100). This
      increase in apoB-48 biosynthesis is reflected by an increase in circulating
      plasma apoB-48 from barely detectable to approximately 50% of total plasma apoB.
      Fractionation of plasma lipoproteins by fast protein liquid chromatography (FPLC)
      indicates that the ethanol-induced hypertriglyceridemia is completely accounted
      for by an increase in plasma very low density lipoprotein (VLDL). The proportion
      of apoB-48 as a percent of total apoB in the VLDL fraction increased from
      approximately 50% in controls to > 90% in ethanol-treated animals. Furthermore,
      there is a strong correlation between plasma triglyceride concentration and
      proportion of edited apoB-mRNA in the liver of ethanol-treated rats, but no
      direct correlation of the latter with intrahepatic triglyceride content. Ethanol
      treated rats represent a new model for studying the regulation of apoB mRNA
      editing by dietary factors in vivo.

PMID- 8576635
TI  - Effect of a coffee lipid (cafestol) on regulation of lipid metabolism in CaCo-2
      cells.
AB  - The influence of cafestol, a lipid component found in boiled coffee, on low
      density lipoprotein (LDL) and lipid metabolism was investigated in CaCo-2 cells
      cultured on filter membranes. The rate of uptake and degradation of 125I-labeled
      tyramine cellobiose-LDL was increased 50% in CaCo-2 cells incubated with cafestol
      (20 micrograms/ml, 63 microM) for 24 h, whereas in cells incubated with 25
      hydroxycholesterol (10 micrograms/ml, 25 microM) the rate of uptake and
      degradation showed a 30% decrease. A mixture of kahweol and cafestol, both
      natural components of coffee beans, modestly enhanced the rate of LDL uptake and
      degradation, as compared to pure cafestol. Incubation of cafestol with CaCo-2
      cells induced a 3-fold up-regulation of LDL receptor mRNA, as compared to control
      cells. In contrast, incubation of the cells with 25-hydroxycholesterol produced a
      30% decrease of LDL receptor expression. CaCo-2 cells were transfected with a
      promoter region containing the sterol regulatory element-1 (SRE-1) coupled to the
      reporter gene chloramphenicol acetyltransferase (CAT). When cells transfected
      with SRE-1 promoter were incubated with cafestol, there was a 20% up-regulation
      of CAT activity, whereas 25-hydroxycholesterol abolished this activity. Cafestol
      contributed to a significantly lowered secretion of cholesteryl ester and
      triacylglycerol, regardless of the radiolabeled precursor used ([2-14C]acetic
      acid, [1,2,3-3H]glycerol, [3H]water, and [1-14C]oleic acid). This reduction in
      secretion of lipids was accompanied by an increase in trichloroacetic acid
      soluble activity when radiolabeled oleic acid was used as a tracer. We conclude
      that cafestol promotes an enhanced rate of uptake and degradation of LDL,
      probably due to an increase in transcription of LDL receptor mRNA and a reduced
      secretion of cholesteryl ester and triacylglycerol in CaCo-2 cells.

PMID- 8576636
TI  - Heterologous expression of apolipoprotein B carboxyl-terminal truncates: a model
      for the study of lipoprotein biogenesis.
AB  - Expression of proteins in cells that lack specific chaperones, or subunits
      required for correct assembly results in the degradation of these proteins early
      on after synthesis, probably in the endoplasmic reticulum (ER) or an ER-related
      compartment. We have explored heterologous expression as a model to study the
      complex process involved in the biogenesis of apolipoprotein B (apoB)-containing
      lipoproteins. As an initial step, a series of carboxyl-terminal truncated apoB in
      COS cells were expressed to characterize this system. ApoB proteins ranging from
      apoB-13 to apoB-41 were expressed. Truncates larger than apoB-29 were completely
      retained and degraded within the cells; hence these cells have a 'secretory
      defect' for the larger truncates. Degradation of these apoB proteins is likely to
      be in the endoplasmic reticulum or ER-related compartment, as shown by
      sensitivity to endo beta-N-acetylglucosaminidase, by lack of an effect on the
      degradation kinetics by brefeldin A treatment, and by ImmunoGold EM. Degradation
      in COS cells was not affected by a variety of protease inhibitors, including N
      acetyl-leucyl-leucyl-norleucinal (ALLN). Addition of oleate to the culture medium
      did not alter their metabolic fate. In comparison to the larger truncates, apoB
      proteins less than apoB-29 were partially secreted; the majority of these, too,
      were also retained and degraded intracellularly in a similar compartment.
      Secreted apoB-17 protein was shown to have been processed correctly in the Golgi
      and was secreted as a minimally lipidated protein. This model, based on the
      expression of apoB truncates larger than B-29 in COS cells, may therefore allow
      for the identification and study of the requirements of specific factors that may
      be required for both apoB secretion and lipoprotein biogenesis by in vivo
      complementation of this 'secretory' defect.

PMID- 8576637
TI  - Interaction of the lipoprotein lipase asparagine 291-->serine mutation with body
      mass index determines elevated plasma triacylglycerol concentrations: a study in
      hyperlipidemic subjects, myocardial infarction survivors, and healthy adults.
AB  - A mutation in the lipoprotein lipase (LPL) gene, resulting in the substitution of
      asparagine by serine at residue 291 (LPL-S291), was found to occur in young
      survivors of a myocardial infarction from Sweden, combined hyperlipidemic
      subjects from the United Kingdom, and type III hyperlipidemic subjects from
      Germany at allelic carrier frequencies no different from those found in companion
      healthy control subjects (3.63 vs. 3.37; 1.85 vs. 1.60; and 2.00 vs. 1.56%,
      respectively). In a group of 620 healthy middle-aged men from the United Kingdom
      with baseline and three subsequent annual lipid measurements, mean plasma
      triacylglycerol (TG), (but not plasma cholesterol) concentrations in carriers of
      the mutation were significantly elevated over non-carriers (1.95 vs. 1.61 mmol/l,
      P = 0.05, and 5.83 vs. 5.65 mmol/l, P = 0.29, respectively). When these healthy
      control subjects were divided according to tertiles of body mass index (BMI), as
      expected, non-carriers whose BMI was in the upper two tertiles (BMI > or = 25.0
      kg/m2) had higher plasma TG concentrations than those in the lowest tertile (1.90
      vs. 1.54 mmol/l), but this difference was much greater in LPL-S291 carriers (2.33
      vs. 1.36 mmol/l, P = 0.01, BMI x genotype interaction, P = 0.02). To confirm this
      effect, a second group of 319 healthy subjects from the United Kingdom was
      screened for LPL-S291. The allelic frequency of the mutation was found to be
      1.88% and the effect on plasma lipid concentrations was very similar to that
      observed in the first control group (plasma TG, 2.31 vs. 1.27 mmol/l, P < 0.001
      for LPL-S291 carriers vs. non-carriers, respectively). As before, those carriers
      whose BMI was in the top two tertiles for this sample (BMI > or = 23.3 kg/m2) had
      higher plasma TG concentrations than non-carriers (2.31 vs. 1.42 mmol/l). Thus,
      the LPL-S291 variant may predispose individuals to elevated plasma TG
      concentrations under conditions such as increased BMI.

PMID- 8576638
TI  - Effect of temperature and phase transition on oxidation resistance of low density
      lipoprotein.
AB  - The study of the effect of temperature on the kinetics of low density lipoprotein
      (LDL) oxidation was carried out by measuring the conjugated diene (CD) versus
      time curves at a fixed LDL concentration (0.1 microM) and at different Cu2+
      concentrations (0.5-10 microM) in a wide temperature range, from 10 degrees C to
      45 degrees C. The core melting point of the LDL determined with differential
      scanning calorimetry was 31.1 degrees C. We have demonstrated that temperature
      exerts a clear effect in the Cu(2+)-mediated LDL oxidation, with a strong
      decrease in lag time and a notable increase in the rate of propagation. This
      temperature dependence of lag time and rate of propagation fully obeys the
      Arrhenius law, suggesting that the core melting point of the LDL has no or only a
      minor effect on these oxidation indices. The Arrhenius plots of the binding of
      Cu2+ to LDL, measured by K, gave two breaks suggesting that this value is
      affected by the core transition of the LDL as well as by structural changes at
      around 15 degrees C. The mean activation energy during rate of initiation was
      13.5 kcal/mol and tended to decrease with increasing Cu2+ concentration. The
      activation energy in the propagation phase was 10.6 kcal/mol and was independent
      of Cu2+ concentration. In this work we have also shown that the CD method can be
      conducted with high reproducibility and that a sucrose-supplemented plasma frozen
      at -80 degrees C can be used as a source of LDL with an unvarying vitamin E
      content and reproducible oxidation properties.

PMID- 8576639
TI  - Lysosomal degradation and sorting of apolipoprotein E in macrophages.
AB  - We previously reported that a substantial amount of newly synthesized apoE in
      mouse macrophages is degraded prior to secretion; a portion of this pool of apoE
      can be rescued by the addition of HDL3 to the incubation medium. In the present
      studies, the location and nature of the intracellular degradation of apoE were
      more closely examined. Inhibitors of protein trafficking (brefeldin A) as well as
      a number of protease inhibitors were used. The experiments using brefeldin A (5
      micrograms/ml) clearly established that neither the endoplasmic reticulum nor the
      Golgi complex are the sites of apoE degradation. Using a pulse-chase design,
      [35S]apoE cannot be chased out in the presence of brefeldin A and remains
      undegraded within the cell. The accumulated apoE lacks the sialic acid residues,
      indicating that this final stage of processing must occur in the trans-Golgi
      network or later. Lysosomotropic agents, ammonium chloride and chloroquine, on
      the other hand, inhibit apoE degradation by over 70 and 80%, respectively, while
      total cell protein degradation remains unaffected. Similarly, a cocktail
      consisting of four lysosomal protease inhibitors (pepstatin, E-64, chymostatin,
      and antipain), inhibits specifically apoE degradation by over 60%. In contrast,
      ALLN, an inhibitor of Ca(2+)-dependent cysteine proteases, has a moderate effect
      on apoE degradation (30% inhibition) and a more pronounced effect on total
      protein degradation. These data suggest that the site of intracellular apoE
      degradation in the macrophage is the lysosome. These conclusions are supported by
      light and electron microscopy of macrophages, clearly showing the presence of
      immunoreactive apoE (along with cathepsin D) in the endosomal/lysosomal
      compartment of control and lysosomotropic agent-treated cells. In contrast,
      little or no labeling is seen in this compartment in brefeldin A-treated cells.
      At lower concentrations of the lysosomotropic agents, the extent of inhibition of
      apoE degradation is compensated for by its increased secretion, in a manner
      analogous to the effect of these agents on lysosomal enzymes. Higher
      concentrations of these agents, which lead to a profound inhibition of apoE
      degradation, also specifically block apoE secretion. The block in apoE secretion
      in the presence of high concentrations of chloroquine leads to undiminished or
      higher concentrations of immunoreactive apoE in the endosomal/lysosomal
      compartment, suggesting that apoE is targeted for lysosomal degradation directly,
      without prior secretion or surface association. These data strongly suggest pH
      dependent sorting of apoE in macrophages to the degradative and secretory
      pathways and imply a protein-protein interaction in the process.

PMID- 8576640
TI  - Lipoprotein lipase gene polymorphisms: associations with myocardial infarction
      and lipoprotein levels, the ECTIM study. Etude Cas Temoin sur l'Infarctus du
      Myocarde.
AB  - Several lipoprotein lipase (LPL) gene polymorphisms have been found associated
      with fasting lipid levels, but their impact on coronary heart disease (CHD) is
      less clearly established. We investigated associations of LPL polymorphisms
      (HindIII, PvuII, Ser447-->Ter) and the newly described mutation Asn291-->Ser with
      the risk of myocardial infarction (MI), severity of atherosclerosis, and fasting
      plasma lipoprotein concentrations in the ECTIM study (614 patients and 733
      controls). The Ter447 allele had a lowering effect on triglycerides (P < 0.01),
      VLDL-cholesterol (P < 0.05), apoC-III (P < 0.001), LpE:B (P < 0.01), and LpCIII:B
      (P < 0.05), and a raising effect on apoA-I levels (P < 0.05). The H- allele of
      the HindIII polymorphism was associated with lower apoC-III (P < 0.01) and higher
      HDL-cholesterol (P < 0.05) levels. The PvuII and Asn291-->Ser polymorphisms did
      not exhibit any significant association with the biochemical traits examined. The
      HindIII genotype distributions differed between cases and controls, the odds
      ratios for MI associated with H+H+ and H+H- genotypes being 2.05 (P < 0.01) and
      1.74 (P < 0.05) by reference to H-H-. The lack of association between Ser447-
      >Ter and MI suggested that this mutation was unlikely to be the cause of the
      association found with HindIII. In some cases, the severity of atherosclerosis
      assessed by coronarography increased with the presence of P+ allele (coronary
      scores: 1.41, 1.57, and 1.64 in P-P-, P-P+, and P+P+ individuals respectively, P
      < 0.05). A similar trend on the coronary score was observed with the presence of
      the Asn291-->Ser mutation (1.58 vs. 1.90, P = 0.06). Our results suggest that the
      LPL gene is involved in the determination of lipoprotein profiles, the
      predisposition to CHD, and the severity of atherosclerosis.

PMID- 8576641
TI  - Imaging biliary lipid secretion in the rat: ultrastructural evidence for
      vesiculation of the hepatocyte canalicular membrane.
AB  - Physical-chemical and biological studies of hepatic bile suggest that biliary
      phospholipid molecules are secreted as unilamellar vesicles. Systematic
      ultrastructural studies of bile canaliculi were undertaken to visualize this
      event. Liver tissue was obtained from normal adult male rats (control), from bile
      salt-depleted rats (by overnight biliary diversion), and from depleted rats
      infused intravenously with a hydrophilic-hydrophobic congener series of common
      taurine-conjugated bile salts. Livers were fixed in situ either by modified
      chemical methods or by ultrarapid cryofixation. In control rats, chemical
      fixation revealed unilamellar vesicles 63 +/- 17 (+/- SD) nm in diameter, mostly
      free within canalicular lumena. Vesicles were infrequent in canaliculi of bile
      salt-depleted rats, but were present in canaliculi of rats infused with
      taurocholate. In cryofixed liver tissue, vesicles 67 +/- 13 nm in diameter were
      observed in canaliculi of control rats and bile-salt depleted rats infused with
      common bile salts. The majority of these vesicles were affixed to the luminal
      side of the canalicular membrane. The average number of vesicles per bile
      canaliculus was in agreement with that estimated on the basis of biliary
      phospholipid secretion rates, mean vesicle size, and area of close-packed
      phosphatidylcholine molecules. By immunoelectron microscopy, canalicular vesicles
      were free of actin and of a 100 kDa canalicular membrane protein. We conclude
      that biliary phospholipid molecules are secreted from hepatocytes into bile
      canalicular lumena as unilamellar vesicles approximately 63-67 nm in average
      diameter. We postulate that this secretion mechanism involves lumenal bile salt
      induced vesiculation of lipid microdomains in the exoplasmic hemileaflet of the
      canalicular membrane.

PMID- 8576642
TI  - Selective mobilization of adipose tissue fatty acids during energy depletion in
      the rat.
AB  - This study extends our previous work (Raclot, T., and R. Groscolas. 1993. J.
      Lipid Res. 34: 1515-1526) which demonstrated that in the fed state fatty acids
      are selectively released from white adipocytes in vitro. It aims at determining
      whether such selectivity operates in vivo during energy depletion and has
      physiological relevance. This question was examined in rats by simultaneously
      measuring, after 1, 7, or 10 days of fasting, the fatty acid content of
      retroperitoneal adipose tissue (RP), and the composition of fatty acids released
      by isolated RP adipocytes. A preliminary dietary manipulation (fish oil feeding)
      allowed us to study the mobilization of a wide spectrum of fatty acids. Fasting
      resulted in a relative depletion of adipose tissue in fatty acids such as alpha
      linolenic, arachidonic, and eicosapentaenoic, and in a relative enrichment in all
      very long chain saturated and monounsaturated fatty acids. After a 56% depletion
      of total fatty acids, 20% (22:1n-11) to 90% (20:5n-3) of the initial mass of
      individual fatty acids was lost. The in vivo relative mobilization of fatty acids
      (% in lost fatty acids / % in RP triacylglycerols) ranged from 0.31 to 2.54. For
      a given chain length it increased with unsaturation whereas for a given degree of
      unsaturation it decreased with chain length. The in vitro relative mobilization
      of fatty acids (% in released fatty acids/% in RP triacylglycerols) was similarly
      dependent on their molecular structure and, to a significant extent, directly
      related to in vivo mobilization. It is concluded that during fasting-induced
      energy depletion, the net in vivo mobilization of fatty acids from adipose tissue
      is selective. The selectivity of mobilization i) is based on the molecular
      structure of fatty acids, ii) is fully accounted for by their selective release
      from adipocytes, iii) leads to a profound remodelling of the composition of
      adipose tissue fatty acids, and iv) does not seem directed towards a preferential
      retention or sparing of particular fatty acids.

PMID- 8576643
TI  - Intravenous lipid emulsions: removal mechanisms as compared to chylomicrons.
AB  - We have compared the metabolism of chylomicrons and a labeled emulsion, similar
      to those used for parenteral nutrition. Both were labeled in their triglyceride
      moieties and by a core label. It is known that chylomicron triglycerides are
      cleared by two processes: removal of triglycerides from the particles through
      lipolysis and removal of whole or partly lipolyzed particles. It has been
      proposed that emulsion droplets are cleared by the same pathways. After
      intravenous injection to postprandial rats, triglycerides were cleared less
      rapidly from the emulsion than from the chylomicrons (half-lives of 6.4 and 4.0
      min), whereas the core labels were cleared at the same rate (half-lives around
      7.5 min). This suggests that there was less lipolysis of the emulsion droplets
      which was further supported by the finding that less label appeared in the plasma
      free fatty acids (FFA). In adipose tissue of fed rats given chylomicrons, the
      ratio between fatty acid and core label was above 6, showing that fatty acids had
      been taken up after lipoprotein lipase-mediated hydrolysis. In contrast, for rats
      given emulsion, that ratio was only 1.2 showing that nearly as much emulsion
      droplets as emulsion-derived fatty acids were present in the tissue. In the liver
      the ratio was 0.55 after chylomicrons but 0.93 after emulsion. In further support
      of more lipolysis, fatty acids were oxidized more rapidly from chylomicrons than
      from emulsion. These data suggest that a large fraction of the emulsion droplets
      was removed from plasma with little or no preceding lipolysis. A substantial
      proportion, more than 50%, of this uptake occurred in extrahepatic tissues.

PMID- 8576644
TI  - Crystal structure of a mixed chain diacylglycerol, 1-stearoyl-3-oleyl-glycerol.
AB  - Diacylglycerols composed of one saturated and one unsaturated chain make up the
      hydrophobic core of many biological membranes. We report here the first
      crystalline structure of such a mixed chain diacylglycerol. The mixed chain
      diacylglycerol, 1-stearoyl-3-oleyl-glycerol (1,3-SODG) was produced by solution
      isomerization of 1-stearoyl-2-oleyl-sn-glycerol. 1,3-SODG was isolated by flash
      chromatography and crystallized by slow evaporation in ethyl acetate at 4 degrees
      C. The melting point was 42.5 degrees C and the enthalpy was 18.0 kcal/mol. The
      crystal structure was determined to a final R factor of 0.127. Four molecules are
      present in the monoclinic unit cell: space group Cc, a = 9.362(2), b = 5.495(2),
      c = 77.92(3)A, beta = 91.46(2), V = 4007(4)A3, Z = 4, D = 1.032 g/cm3. The
      molecule forms an extended V-shaped conformation with the oleate and stearate
      chains coming off the two ends of the glycerol with an angle between their planes
      of 94 degrees. The two chains pack separately in individual layers and do not
      interact. The hydrogen bonds between the free hydroxyl group on the glycerol-2
      position and the carbonyl oxygen on the oleyl chain of an adjacent molecule are
      2.78 A in length and stabilize the glycerol layers. The stearoyl chain is roughly
      straight and packed in a triclinic parallel subcell. Both portions of the oleyl
      chain also pack in triclinic parallel packing. The torsion angle sequence along
      the double bond extending from the oleyl carbons C7 to C13 is tscsst (173
      degrees, -152 degrees, -17 degrees, -157 degrees, -163 degrees, -178 degrees).
      This sequence is different from other monounsaturates. The torsion angle sequence
      around the glycerol region shows that the glycerol conformation is quite similar
      to the A conformer of racemic alpha monolaurin, and to 1,3-di-11-bromoundecanoyl
      glycerol, but completely unlike 1,2-diacyl-sn-glycerols. Thus the glycerol
      conformation appears to be driven by the hydrogen bond formation, which in turn
      determines whether chains interact or are segregated. In 1,3-diacylglycerols the
      two acyl chains point in different directions and are segregated. In 1,2
      diacylglycerols the acyl chains lie side by side and must interact. When the two
      chains are quite different, then serious problems in packing occur, giving rise
      to disordered crystal packing. Probably as a result of the disordered chain
      packing in 1-stearoyl-2-oleyl-sn-glycerol (Di, L. and D.M. Small. 1993. J. Lipid
      Res. 34: 1611-1623) we were not successful in growing adequate crystals suitable
      for crystallographic structure determination of this 1,2 mixed chain
      diacylglycerol.

PMID- 8576645
TI  - Gender differences in response to dietary soluble fiber in guinea pigs: effects
      of pectin, guar gum, and psyllium.
AB  - Dietary soluble fiber significantly lowers plasma low density lipoprotein (LDL)
      cholesterol concentrations in humans and animals. In male guinea pigs,
      alterations in hepatic cholesterol homeostasis induced by dietary fiber in part
      account for the decrease in plasma LDL levels (Fernandez et al. 1994. Am. J.
      Clin. Nutr. 59: 869-878; 1995. 61: 127-134, and J. Lipid Res. 1995. 36: 1128
      1138). To test whether dietary fiber elicited similar hypocholesterolemic
      responses in both genders, female guinea pigs were fed diets containing 12.5%
      pectin (PE), 12.5% guar gum (GG), 7.5% psyllium (PSY), or 12.5% cellulose
      (control diet). In addition, physiological (0.04%) (LC) or pharmacological
      (0.25%) (HC) amounts of cholesterol were tested with the fibers to determine
      whether dietary cholesterol altered the plasma cholesterol response. Significant
      reductions in plasma cholesterol were observed in females fed LC diets with PE,
      GG, or PSY (P < 0.01) while the responses to fiber with high cholesterol intake
      were more moderate. Hepatic cholesterol concentrations were reduced in the LC
      group (P < 0.001) with increased HMG-CoA reductase and cholesterol 7 alpha
      hydroxylase and decreased acyl CoA:cholesterol acyltransferase (ACAT) activities
      accompanied by a reduction in hepatic cholesterol pools induced by fiber intake.
      In addition, plasma LDL lowering in animals fed the LC diets was associated with
      increases in hepatic LDL receptor Bmax values. Effects of fiber on hepatic
      cholesterol in animals fed HC diets were moderate and hepatic enzymes were not
      altered to the same extent as in the LC groups. For the LC groups there was no
      gender effect on the magnitude of plasma LDL lowering, depletion of hepatic
      cholesterol, or alterations in hepatic cholesterol metabolism, although hepatic
      HMG-CoA reductase and ACAT activities were lower in females compared to males (P
      < 0.01). In contrast, females fed the control HC diet had higher plasma LDL
      levels than males and dietary fiber did not reduce hepatic cholesterol
      concentrations nor alter hepatic enzyme activities as effectively as in males.
      These studies demonstrate that female, compared to male, guinea pigs are more
      responsive to a dietary cholesterol challenge and, that with this pharmacological
      perturbation, fiber effects are moderate compared to males. In contrast, with low
      cholesterol intakes, the cholesterol lowering effects of fiber are similar in
      both genders.

PMID- 8576646
TI  - Cellular cysteine generation does not contribute to the initiation of LDL
      oxidation.
AB  - It has been suggested that the generation of cysteine (Cys-SH) by cells may play
      a role in the initiation of oxidation of low density lipoprotein (LDL). Cysteine
      has long been considered as an antioxidant. We studied the effect of Cys-SH on
      the oxidation of LDL by copper. The presence of Cys-SH had a profound inhibitory
      effect on the formation of conjugated dienes when fresh LDL was used. However,
      when we used LDL samples that were subjected to pre-incubation with copper, a
      progressive decrease in the inhibition and an actual enhancement of oxidation by
      Cys-SH could be demonstrated. The oxidation of freshly prepared LDL by RAW
      macrophages as compared to older LDL was considerably less. The addition of Cys
      SH inhibited the oxidation of LDL by cells. In contrast, the addition of cystine
      (Cys-S-S) enhanced the oxidation of older LDL preparations while such additions
      had no effect on the oxidation of freshly prepared LDL. When pre-incubated LDL
      was subjected to oxidation by cells an enhancement of oxidation by Cys-S-S could
      be noted. These results demonstrate that the role of Cys-SH generated as a result
      of cellular recycling of Cys-S-S in the oxidation of LDL may not relate to the
      initiation of oxidation reactions. However, Cys-SH may enhance the rate of
      oxidation of LDL that may contain peroxides.

PMID- 8576647
TI  - Cloning of rat lysosomal acid lipase cDNA and identification of the mutation in
      the rat model of Wolman's disease.
AB  - Lysosomal acid lipase (LAL) is a hydrolase essential for the intracellular
      degradation of cholesteryl esters and triglycerides. We previously reported a rat
      model of Wolman's disease (Wolman rat) that is deficient for LAL activity. In
      this study, we cloned rat LAL (RLAL) cDNA and investigated abnormal LAL gene
      expression in the Wolman rat. We cloned the RLAL gene from a cDNA library made
      from normal rat liver mRNA using the human LAL cDNA as a probe, subcloned the
      RLAL cDNA into pBlueScript vector, and sequenced it. Next, we constructed a cDNA
      library from a Wolman rat liver, and used the RLAL cDNA as a probe to isolate the
      Wolman RLAL cDNA for comparison. The normal RLAL cDNA contains 3150 bp including
      an 1194 bp open reading frame and three poly A signals at the 3' end. The deduced
      amino acid sequence contained 397 amino acids, showed 79.9% homology with human
      LAL, and had the same functional domains at the same sites as human LAL. Northern
      blot analysis revealed that the RLAL mRNA from normal rat was 3.2 kb in length,
      while the RLAL mRNA from Wolman rat was only 1.4 kb. Nucleotide sequence analysis
      showed that Wolman rat LAL cDNA had the same sequence as a RLAL cDNA from the 5'
      untranslated region to nt 1101, followed by a 60 bp replacement from nt 1102 to
      nt 1161 with poly A signal and a 3' 1.8 kb deletion. The deduced amino acid
      sequence demonstrated the substitution of 367Ile to Asn, 368Pro to stop codon,
      and deletion of the C-terminal 29 amino acids. Genomic Southern blot analysis
      disclosed a large deletion at the 3' end of the gene. These results identify the
      molecular defect in the Wolman RLAL, and suggest that the C-terminus of RLAL is
      essential for the activity and/or stability of the enzyme.

PMID- 8576648
TI  - Interactions between adipose tissue around lymph nodes and lymphoid cells in
      vitro.
AB  - The functional relationships between lymphoid cells and the adipose tissue that
      surrounds lymph nodes were investigated in healthy adult guinea pigs. Lymphoid
      cells extracted from healthy adult guinea pigs were co-cultured for 48 h with
      adipose tissue explants from 18 sites defined by their anatomical relations to
      lymph nodes. Such explants from near a node suppressed lymphocyte proliferation
      stimulated with concanavalin A or lipopolysaccharide more than those from sites 5
      10 mm from nodes. Inhibition was almost completely abolished by 500 microU
      insulin. The presence of lymphoid cells increased lipolysis (measured as glycerol
      release) in adipose tissue from all depots containing lymph nodes (i.e., except
      perirenal), especially in the presence of mitogens and with near-node samples
      from intermuscular and mesenteric depots. Inhibition of lymphocyte proliferation
      by adipose tissue was proportional to the additional lipolysis stimulated by the
      presence of lymphoid cells. For all depots except the mesenteric, glycerol
      release stimulated by lymphoid cells was inversely proportional to spontaneous
      lipolysis in adipose tissue cultured alone. These experiments demonstrate
      reciprocal interactions between lymphoid cells and adipose tissue, especially
      that around lymph nodes. The mediators of the action of adipose tissue on
      lymphoid cells probably include lipolytic products; mediators of the inverse
      effects are unknown.

PMID- 8576649
TI  - Components of the protein fraction of oxidized low density lipoprotein stimulate
      interleukin-1 alpha production by rabbit arterial macrophage-derived foam cells.
AB  - Oxidized low density lipoproteins (oxLDL) (0.5-50 micrograms/ml) generated from
      both rabbit and human LDL stimulated the production of interleukin-1 alpha (IL-1
      alpha) by as much as 2- and 6-fold, respectively, as compared to native LDL after
      a 2-h incubation with macrophage-derived foam cells isolated from the balloon
      injured arteries of cholesterol-fed rabbits. Northern blot analyses confirmed
      that there was also an increase in the mRNA for IL-1 alpha and IL-beta in
      response to oxLDL in the isolated foam cells. The stimulation of IL-1 expression
      and production was not due to the contamination of the oxLDL preparations with
      endotoxin as neither the amount of endotoxin found to be associated with the
      lipoproteins nor amounts up to 1 ng/ml stimulated IL-1 alpha production to the
      same degree as oxLDL. Neither oxidized beta-very low density lipoprotein (VLDL)
      nor oxidized high density lipoprotein (HDL) stimulated IL-1 alpha production by
      the foam cells. Furthermore, acetyl-LDL had a very limited stimulatory effect,
      but other known ligands of the scavenger receptor such as maleylated-BSA,
      polyinosinic acid, and fucoidin elicited maximal IL-1 alpha responses.
      Fractionation of the oxLDL into lipid- and protein-soluble fractions showed that
      there was some stimulatory activity in the lipid phase but that known products of
      lipid peroxidation such as 9- and 13-HODE had no effect when added independently
      of lipoproteins. When added in combination with native LDL, only 13-HODE
      stimulated IL-1 alpha production. The delipidated apolipoprotein fragments of
      oxLDL that had been solubilized in beta-octylglucoside stimulated the production
      of IL-1 alpha by the foam cells to a greater degree than the lipid extract, while
      reductively methylated oxLDL did not. These data suggest that interactions of
      components of both the lipid- and protein-soluble fractions of oxLDL with
      scavenger receptors or potentially with surface proteins that bind oxLDL may
      induce production of IL-1 by arterial macrophages.

PMID- 8576650
TI  - A sensitive method to analyze in vitro secretion of lipoproteins: distribution of
      apolipoproteins is modulated by oleic acid in HepG2 cells.
AB  - Lipoprotein metabolism can be studied by the analysis of lipoprotein production
      in cell culture. An inherent problem in such an analysis is the low concentration
      of lipoproteins in culture supernatants. The difficulty comes from the fact that
      the samples must be concentrated prior to any analysis. The concentrating methods
      (e.g., dialysis or ultrafiltration) induce a heterogeneous loss of components. In
      order to minimize these losses, we have developed a sensitive three-step method
      to analyze the distribution and the amount of apolipoproteins in the different
      classes of lipoproteins secreted by the human hepatoma cell line HepG2. Cells
      were labeled with [14C]acetate and [35S]methionine for 4 h in the presence of
      0.08 mM BSA, complexed or not, with 0.75 mM oleic acid. The 14C-radiolabeled
      cellular lipids were extracted and analyzed by thin-layer chromatography and the
      secreted lipoproteins were analyzed by the following three-step method. First,
      the lipoproteins were isolated by flotation ultracentrifugation. Second, total
      lipoproteins were directly applied to native agarose-acrylamide gel
      electrophoresis in order to separate lipoproteins with respect to their diameter.
      After migration, the gel was sliced and each fragment was eluted in a buffer
      containing sodium dodecyl sulfate and analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. This allowed evaluation of the proportion of
      apolipoproteins in lipoproteins. Oleic acid (0.75 mM) increased the rate of
      triglyceride biosynthesis and apoB-100 secretion by 1.7-fold and 2.4-fold,
      respectively. Moreover, oleic acid treatment modified the profile of secreted
      lipoproteins. Oleic acid-treated cells secreted more apoB-100 within VLDL than
      control cells.

PMID- 8576651
TI  - Immobilized artificial membrane chromatography: a rapid and accurate HPLC method
      for predicting bile salt-membrane interactions.
AB  - To predict bile salt-membrane interactions physiologically, we used an
      immobilized artificial membrane HPLC column that contains dimyristoyl
      phosphatidylcholine molecules covalently linked to silica microspheres. Using a
      90% aqueous (10% acetonitrile) mobile phase, 22 species of bile salts and 4
      species of fusidates were eluted. Glycine conjugates displayed higher affinity
      for the column at pH 5.5, eluting later than their taurine-conjugated congeners,
      but this order was reversed at pH 6.5 and 7.4 as glycine conjugates became fully
      ionized. Capacity factors decreased logarithmically as functions of increasing
      temperature, permitting determinations of interaction enthalpies, which ranged
      from -2.86 to -7.67 kcal/mol. A standard curve was developed from which the
      enthalpy for an uncommon bile salt could be inferred from its capacity factor at
      room temperature. Bile salt interaction enthalpies were substantially better
      correlated than hydrophobic indices by octadecylsilane-HPLC (D. M. Heuman, J.
      Lipid Res. 1989. 30: 719-730) with equilibrium binding to small unilamellar
      vesicles and literature values reflecting bile salt-membrane interactions (e.g.,
      biliary phosphatidylcholine secretion), but not with bile salt functions that do
      not require phospholipid (e.g., micellar cholesterol solubility). This new
      application should prove valuable for evaluating membrane-active physical
      chemical properties as well as therapeutic potential of novel bile salts,
      particularly when they are available in quantities too small for study by
      conventional techniques.

PMID- 8576652
TI  - Cholesterol quantitation by GLC: artifactual formation of short-chain steryl
      esters.
AB  - A simple and rapid method for the quantitation of total cholesterol in lipid
      extracts using gas-liquid chromatography is presented here as a modification of
      an earlier saponification procedure (Ishikawa, T. T., J. MacGee, J. A. Morrison,
      and C. J. Glueck. 1974. Quantitative analysis of cholesterol in 5 to 20
      microliters of plasma. J. Lipid Res. 15: 286-291). Using the original method, as
      well as a slightly modified version, we found a systematic loss of cholesterol
      measured as total cholesterol that was attributable to the formation of a
      byproduct during the procedure. Depending on the nature of the solvent mixture
      used for extraction after saponification, different byproducts were produced that
      had longer retention times than cholesterol. The byproducts were identified as
      cholesteryl butyrate (produced when methyl butyrate was included in the solvent
      mix) and cholesteryl propionate (with ethyl propionate in the solvent mix) by
      comparison to authentic standards using gas chromatography-mass spectroscopy.
      Using mixtures of cholesterol standards, we compared several solvents in lieu of
      the solvent mixture used in the original extraction procedure to identify those
      that eliminate the formation of the byproducts. Our optimized microsaponification
      procedure uses a single solvent, tetrachloroethylene, to extract lipids after the
      saponification reaction, and improves the accuracy of the cholesterol
      determination.

PMID- 8576653
TI  - Evaluation of the use of beta-sitostanol as a nonabsorbable marker for
      quantifying cholesterol absorption.
AB  - For over a decade investigators have quantified cholesterol absorption by
      comparison of dietary intake and fecal excretion of isotopic cholesterol with
      that of beta-sitosterol as a "nonabsorbable" marker. However, beta-sitosterol
      might not be ideal due to its potential for absorption. We therefore carried out
      two studies to evaluate a new marker with less potential for absorption, [3H]beta
      sitostanol. In the first study (Study I, n = 22), we compared absorption of
      [3H]beta-sitostanol and [14C]beta-sitosterol in a simultaneous dual-label
      continuous feeding ("phytosterol absorption") experiment. We observed a
      consistently higher ratio of [3H]beta-sitostanol/[14C]beta-sitosterol in the
      stool relative to diet on the first day of fecal collection (6.1% +/- 3.2% loss
      of [3H]beta-sitosterol, range 3-12%), but thereafter, the ratio in stool was
      similar to that in diet. In Study II (n = 23), we compared cholesterol absorption
      directly using [3H]beta-sitosterol and [14C]cholesterol, and, separately,
      [3H]beta-sitostanol and [14C]cholesterol. We found that mean absorption between
      the two methods was similar (45% +/- 11% versus 44% +/- 10%, respectively, P
      difference = 0.40), and the two methods correlated well with one another (r =
      0.83) when samples from all available days were used. Variability between the two
      methods was greater in individuals who absorbed more than 40% of cholesterol.
      Cholesterol loss on day 2 estimated from use of beta-sitostanol as a
      nonabsorbable marker was predictive of absorption using ratios from days 4-6 (r =
      0.80). These results suggest that, for the majority of subjects, beta-sitosterol
      is a valid nonabsorbable marker for cholesterol absorption.

PMID- 8576654
TI  - An SIS epidemic model with variable population size and a delay.
AB  - The SIS epidemiological model has births, natural deaths, disease-related deaths
      and a delay corresponding to the infectious period. The thresholds for
      persistence, equilibria and stability are determined. The persistence of the
      disease combined with the disease-related deaths can cause the population size to
      decrease to zero, to remain finite, or to grow exponentially with a smaller
      growth rate constant. For some parameter values, the endemic infective-fraction
      equilibrium is asymptotically stable, but for other parameter values, it is
      unstable and a surrounding periodic solution appears by Hopf bifurcation.

PMID- 8576655
TI  - The protective effect of inhaled terbutaline, sodium cromoglycate and budesonide
      on exercise-induced asthma in children.
AB  - The effect of single-dose inhaled terbutaline, sodium cromo-glycate and
      budesonide were compared with control in 11 exercise-induced asthma (EIA)
      patients, aged 9-14 years. Patients exercise for 6 minutes, 15 minutes after
      inhaling drugs. The FVC, FEV1, PEFR and MMEF were recorded before exercise and
      after exercise at 5 minutes interval up to 25 minutes. After exercise, the mean
      (SEM) maximal percentage fall in FEV1 after placebo, 200 micrograms of
      terbutaline, 10 mg of sodium cromoglycate, and 100 micrograms of budesonide were
      22.81 (3.45), 4.05 (2.11), 11.29 (1.18), and 20.36 (2.33) respectively. It was
      concluded that single-dose inhaled terbutaline and sodium cromoglycate resulted
      in a significant protective effect on exerxide-induced asthma whereas budesonide
      did not.

PMID- 8576656
TI  - Clinical effect of dynorphin on heroin addicts.
AB  - This study assessed the clinical effectiveness, physiological responses and also
      adverse effects of dynorphin in heroin dependent detoxication. The subjects were
      randomly assigned into three groups and received intravenous injections of
      dynorphin at the dose of 180 (6 patients) or 60 (7 patients) or 0 (8 patients)
      micrograms/kg three times a day for 6 days. There was no statistical difference
      in withdrawal syndrome between each group. However, the drug craving feeling in
      the dynorphin groups was reduced when compared to the placebo group. There was no
      report of any adverse effects of the drug or abnormal laboratory results from the
      subjects during the study period.

PMID- 8576657
TI  - Ages at thelarche and menarche: study in southern Thai schoolgirls.
AB  - Ages at thelarche and menarche have been studied by a status quo method in 3,029
      Thai schoolgirls in Hat Yai municipality. The median ages at thelarche and
      menarche estimated by probit analysis are 9 years 11 months, and 12 years 5
      months, respectively. Declining in ages of thelarche and menarche is observed and
      can be explained by improvement in nutritional status and higher living
      standards.

PMID- 8576658
TI  - Effects of law promulgation for compulsory use of protective helmets on death
      following motorcycle accidents.
AB  - This study revealed a significant decrease in mortality from injuries sustained
      by motorcycle accidents following the decree promulgated in 1992 for compulsory
      use of safety helmets by motorcyclists and pillion riders. The helmets can help
      only in protection of head injury but do not affect the number of accidents. This
      safety device can not protect any serious injuries of the neck, chest or internal
      organs which could result in death or permanent disability. To gain maximum
      benefit from the law, the helmets should be of standard specification and worn
      properly. Education to drivers and pillion riders particularly male adolescents
      is essential in reducing the incidence of motorcycle accidents.

PMID- 8576659
TI  - The screening for gestational diabetes employing 50 g glucose test.
AB  - A 50 g 1-h glucose test was studied in pregnant Thai women in order to find out
      the cut-off level for diagnosis of gestational diabetes. The gold standard for
      diagnosis of gestational diabetes. The gold standard for diagnosis of gestational
      diabetes was the standard OGTT. Among 23 patients diagnosed as having gestational
      diabetes following employing a standard test the cut-off value of 144 mg/dl
      accounted for the appropriate level for screening of gestational diabetes.

PMID- 8576660
TI  - Patient-controlled analgesia in Thai patients.
AB  - We conclude that the intravenous PCA method is acceptable, easy to use, does not
      depend on the patients' level of education, and is safe for Thai patients. The
      average pain scores at 48 hours postoperation of the PCA group was significantly
      lower than for the conventional and the I.M. groups. Satisfaction was quite
      difficult to assess. Thai culture might influence how much pain is accepted and
      the patients had not experienced other techniques, so they could not make a
      comparison. The amount of morphine used by the PCA group was intermediate between
      that used by the other two groups.

PMID- 8576661
TI  - Does furosemide prevent hypertension during perioperative splenectomy in
      thalassemic children?
AB  - Hemodynamic changes of 50 thalassemic children who had splenectomy under general
      anesthesia were compared to 40 identical patients who, in addition, received
      intravenous furosemide 1 mg/kg immediate preoperation. During the anesthetic
      process, both groups showed a significant increase of heart rate, systolic and
      diastolic blood pressure more than the preanesthetic values. Hemodynamic
      variables in the furosemide group declined toward normal range on termination of
      anesthesia, whereas, the other group's variables were still significantly higher
      than their control. During the first 24 hours postoperatively, 20 per cent of the
      furosemide group had blood pressure rising higher than 130/90 mmHg, while 18 per
      cent was observed in the other group. Antihypertensive drugs were given to reduce
      the blood pressure in both groups. None of the patients in the furosemide group
      demonstrated any abnormal neurological symptoms, but 3 out of 50 patients in the
      other group developed convulsion. We, therefore, conclude that circulatory volume
      reduction with furosemide does not prevent hypertension during perioperative
      splenectomy in thalassemic children. However, it's role in prevention of
      neurological abnormalities needs to be further investigated.

PMID- 8576662
TI  - Postoperative nausea vomiting (PONV): influence of bowel manipulation during
      intraabdominal surgery.
AB  - This study does not confirm the hypothesis that "bowel manipulation during
      intraabdominal surgery may release 5 HT3 to stimulate the vomiting center via the
      vagus nerve". Thus routine prophylactic use of 5 HT3 receptor antagonist is
      probably not necessary, especially in Thai patients whose PONV is not distinct
      both in incidence and intensity of emesis.

PMID- 8576663
TI  - Screening for urinary amphetamine in truck drivers and drug addicts.
AB  - Sixty-two urine samples from truck drivers and drug addicts were analysed by TDx
      (Abbott Laboratories) for amphetamines. Eighteen samples were found to be
      positive while the rest were negative. The eighteen samples were simultaneously
      determined for amphetamines by EMIT (Syva Company). Sixteen samples were found to
      be positive and 2 of negative samples had amphetamines levels of 0.48-0.85
      micrograms/mL. When the same samples were subjected to qualitative screening and
      some were found false negative as follows: 7 cases in Color Test by using test
      solution kits amphetamine in urine (the Department of Medical Science, Ministry
      of Public Health), 8 cases by Albuscreen Ontrax for amphetamine (Roche Diagnostic
      System), 5 cases by amphetamine Double Antibody 125I-RIA (Diagnostic Products
      Corporation-DPC) and 3 cases by the method of Ten-One (DPC) respectively. But
      when forty four samples which gave negative results by TDx were subjected to
      Testing by EMIT and Ontrax. The results of both EMIT and Ontrax were negative.
      Some of forty four samples were false positive by the Color Test solution kit
      amphetamines in urine and amphetamine Double Antibody 125I-RIA. Reliability of
      results reported not only depends on the methodology or principle but also the
      sensitivity of the method.

PMID- 8576665
TI  - Treatment of giant-cell tumor of the spine: report of four cases.
AB  - Four patients who had a giant-cell tumor of the spine were managed in Ramathibodi
      Hospital from 1986 to 1993. All of the patients are female and the age onset was
      between 14-36 years. The location of the lesions was distributed in the sacrum (2
      cases), lumbar spine (1 case) and cervical spine (1 case). Surgical approach was
      determined by the location, extent of involvement and feasibility of marginal
      resection. Anterior approach was performed in cases of tumor mass confined to the
      vertebral body and posterior approach was done in cases of posterior neural arch
      involvement. Adjuvant therapy and preoperative internal iliac artery ligation
      contributed to successful treatment in cases of sacral involvement. After follow
      up of fifteen to fifty months (average, 30 months), the pain subsided and neural
      symptoms improved. Roentgenograms showed no evidence of local recurrence.

PMID- 8576664
TI  - A therapeutic community for HIV-infected persons: an approach for prevention and
      control of AIDS.
AB  - The Therapeutic Community (TC) for HIV-infected persons is neither a hospital nor
      a confinement for people with HIV. Actually it is a family of friends who are in
      the same boat and a place of education to teach them about AIDS and relevant
      subjects necessary for their life in the future, and to help establish new values
      and life styles for them using TC tools which are adapted from the DAYTOP TC in
      U.S.A. The purpose was not only to build the residents, but also to encourage
      them to do their part in contributing to build up a better and safer society that
      will help to save the lives of others from AIDS. Correct knowledge in AIDS,
      together with the quality of honesty, responsibility and other basic attitudes
      that the residents acquire through the program will enable them to become a
      creative force in the prevention and control of AIDS. The author would say that
      words alone will not describe the whole TC. It requires self experience through
      the program in order to learn TC and understand it.

PMID- 8576666
TI  - Bone changes in postmenopausal Thai women with or without hormonal replacement
      therapy.
AB  - Bone mass measurement was performed in 95 healthy postmenopausal women to assess
      the effect of hormonal replacement therapy (HRT) on bone changes. Women in the
      study group (51/95) received estrogen with or without progestin. The control
      group (44/95) did not receive any hormone regimen. The measurement was done at
      lumbar spines (L1-L4) and hip by dual energy X-ray absorptiometer at 0, 6 and 12
      months. The results revealed significantly higher per cent changes of bone
      density of lumbar spines and hip, at 12 months, in the study group than in the
      control. ( STUDY: Lumbar Spine +1.76%, Hip +3.57%; CONTROL: Lumbar spines -2.32%,
      Hip +1.32%, P < 0.05). In conclusion, this study showed the value of hormonal
      replacement therapy for prevention of postmenopausal bone loss in Thai women.

PMID- 8576667
TI  - Effects of alpha-glucosidase inhibitor (acarbose) combined with sulfonylurea or
      sulfonylurea and metformin in treatment of non-insulin-dependent diabetes
      mellitus.
AB  - The effects of alpha-glucosidase inhibitor (acarbose) were studied in 36 patients
      with non-insulin-dependent diabetes mellitus (NIDDM), aged 34-67 years with a
      mean duration of diabetes of 8.8 +/- 0.9 years. They were poorly controlled with
      diet plus sulfonylurea alone or plus sulfonylurea combined with metformin drugs.
      Acarbose, 100 mg three times daily, was additionally given to these patients for
      six months. Results showed small but significant decreases (P < 0.001) in
      postprandial blood glucose level. Glycosylated hemoglobin level was lowered
      significantly (P < 0.001) and was normalised (level of < 8%) in 17 per cent of
      the patients. Fasting serum triglycerides level decreased significantly (P <
      0.01), whereas, no significant changes in serum total cholesterol and HDL
      cholesterol levels were seen. Body weight also decreased significantly (P <
      0.001) at the end of acarbose trial. Flatulence was the major side effect of
      acarbose found in 42 per cent of the patients but it was well-tolerated and may
      be transient and self-limited. We concluded that the addition of acarbose to the
      therapeutic regimens of diet therapy plus sulfonylurea or plus sulfonylurea
      combined with metformin drugs led to significant improvement of glycemic control.
      Acarbose may be a safe and valuable adjunct to diet and sulfonylurea and
      metformin treatments in obese, poorly-controlled patients with NIDDM.

PMID- 8576668
TI  - Mean platelet volume of normal pregnant women and severe preeclamptic women in
      Siriraj Hospital.
AB  - This study only shows that MPV in severe preeclamptic women is statistically
      greater than in normal pregnant women. The increase in MPV occurs while there are
      still no changes in platelet number. MPV may be better and more sensitive than
      platelet number in detecting changes in platelets. This may be useful in high
      risk patients. The study neither reveals that increase in MPV antecedes the
      development of preeclampsia nor can it predict the severity of the disease. There
      should be further prospective studies on MPV in the future both in preeclamptic
      women and normal pregnant women.

PMID- 8576669
TI  - The use of low dose 1.5 mg prostaglandin E2 gel for cervical ripening and
      induction of labor at term with unfavorable cervix.
AB  - A prospective study was undertaken to evaluate the efficacy and safety of a 1.5
      mg prostaglandin E2 gel applied intracervically for the initiation of cervical
      ripening before the induction of labor. All patients were required to have an
      initial Bishop score of four or less. There was a total of 220 pregnant women in
      this study and primipara accounted for 175 or 80 per cent of the pregnant women.
      The 1.5 mg PGE2 gel was found to be an effective means of cervical ripening in
      both primipara and multipara with a success rate of 77.7 and 93.3 per cent after
      the first application to 96 and 100 per cent in the second application,
      respectively. The mean induction to delivery time was 25.17 hours in primipara
      and 13.57 hours in multipara. The mean amniotomy to delivery time was 7.55 and
      4.65 hours in primipara and multipara, respectively. The cesarean section rate
      was 48 per cent and 18 per cent in primipara and multipara, respectively. The
      side-effects were minimal. These results compare well with other reported studies
      using different dosages and routes.

PMID- 8576670
TI  - A comparative study between pelvic ultrasonography and laparoscopy in the
      detection of pelvic pathology in the initial workup of subfertile women.
AB  - This study was conducted prospectively from June 1992 to September 1993, we
      evaluated 115 patients attending our infertility clinic for the first time to
      determine the correlation between abdominal ultrasound and laparoscopy in the
      detection of pelvic pathology in the initial workup of subfertile women,
      depicting laparoscopy as the gold standard. Normal ultrasound scans were reported
      in 80 women (69.56% of total) 58 of whom had also normal pelvic findings at
      laparoscopy. The remaining 22 patients with normal ultrasound scans had abnormal
      laparoscopic findings in the pelvis giving a false negative rate of 27.50 per
      cent. These were primarily related to; endometriosis with adhesions (10), filmy
      adnexal adhesions (5), omental and bowl adhesions (5), and hydrosalpinx (2).
      Thirty five women (30.44% of the total) had abnormal scans. Pelvic pathologies
      were confirmed in 30 at laparoscopy. The remaining five had a normal pelvis
      (three retroverted uteri, and two functional ovarian cyst had disappeared at time
      of laparoscopy) giving a false positive rate of 14.29 per cent for ultrasound
      scans. Statistical analysis revealed that abdominal ultrasound scan in the
      detection of pelvic pathology in the initial workup of subfertile women has a
      sensitivity of 57.69 per cent, specificity of 92.06 per cent, positive predictive
      value of 85.71 per cent with negative predictive value of 72.50 per cent and
      accuracy rate of 76.52 per cent. We conclude that the use of abdominal ultrasound
      in the detection of pelvic pathology in the initial workup of subfertile women is
      not an appropriate routine screening test as it has low efficiency in detecting
      the pelvic pathologies many of which are the causes of infertility.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8576671
TI  - Cost-effectiveness analysis of patient-controlled analgesia, intramuscular q.i.d.
      injection and p.r.n. injection for postoperative pain relief.
AB  - We conclude that the intravenous PCA method is a cost-effective technique.
      Although the PCA device is expensive, the cost-effectiveness analysis should give
      explicit figures for physicians and the hospital administrators to decide whether
      they should use the PCA instead of the conventional method.

PMID- 8576672
TI  - Combined thoracic epidural with light general anesthesia for thymectomy in
      myasthenia gravis.
AB  - Forty-seven myasthenia gravis patients undergoing transsternal thymectomy were
      allocated into 2 groups. Group 1 which consisted of 27 patients was anesthetized
      using the balanced technique, while 20 patients in group 2 received the
      combination of thoracic and balanced anethesia. The ventilation was controlled
      through the endotracheal tube in both groups. The extubation criteria after
      performing the surgery were good consciousness, adequate muscle strength and
      adequate respiration. There were 29.2 per cent in group 1 but 77.8 per cent in
      group 2 (P = 0.002) with successful extubation immediately postoperation.
      Morphine 15.4 +/- 5.3 mg intramuscularly in group 1, and 6.5 +/- 1.2 mg
      epidurally in group 2 (P < 0.001) was given for postoperative analgesia. Adequacy
      of respiration was observed postoperatively in the intensive care unit (ICU).
      Group 1 patients required 76.9 per cent of further ventilatory support for the
      period of 37.11 +/- 39.54 hours and duration of the ICU stay was 65.52 +/- 85.84
      hours, whereas, the patients in group 2 showed significantly different results,
      which were 15.8 per cent of ventilatory support (P = 0.002) for 10.33 +/- 6.03
      hours (P = 0.014) and 22.8 +/- 8.06 hours for staying in ICU (P = 0.021). This
      study demonstrated that the combined thoracic epidural with light general
      anesthesia provides excellent intraoperative anesthesia together with
      postoperative analgesia, which reduces the need for postoperative respiratory
      support, as well as decreases the hospital cost.

PMID- 8576673
TI  - Seroprevalence of anti-HCV among HIV-infected persons and general population.
AB  - From November 1993 to December 1994, the seroprevalence of anti-HCV, HBsAg was
      studied among 346 HIV-infected persons (asymptomatic HIV-infected persons and
      AIDS patients) and 1,023 subjects from the general population (including 119 cord
      blood samples). The prevalence of anti-HCV, HBsAg among HIV-infected patients
      aged 15-45+ years was 11.0 and 11.6 per cent respectively which is significantly
      higher than the comparable levels for the general population (1.9% and 4.7%) in
      the age group 15-44 years. There was no statistically significant association of
      anti-HCV and HBsAg prevalence among 200 asymptomatic HIV-infected carriers and
      146 AIDS patients. Assays for anti-HCV among blood donors are highly recommended
      to reduce the development of liver disease or cirrhosis in the immediate future.

PMID- 8576674
TI  - A controlled clinical trial of multidisciplinary team approach in the general
      medical wards of Chulalongkorn Hospital.
AB  - The benefits and acceptability of a strengthened physician-nurse collaboration
      and a multidisciplinary team approach are demonstrated in the medical wards of a
      Thai acute-care hospital (Chulalongkorn University Hospital). The strengthened
      physician-nurse collaboration should be introduced or strengthened in all medical
      wards. Because of the lack of appropriately trained personnel, concentrating
      resources into a small unit or ward may be the appropriate measure at present if
      a multidisciplinary team approach is to be integrated into the medical ward of
      acute-care hospitals in South East Asia.

PMID- 8576675
TI  - Treatment of herpes zoster with Clinacanthus nutans (bi phaya yaw) extract.
AB  - A randomized, placebo-controlled trial of the efficacy of topical formulation of
      Clinacanthus nutans (Bi Phaya Yaw) extract was carried out in 51 patients with
      varicella-zoster virus infection. The study medication was applied five times
      daily for 7-14 days until the lesions were healed. The number of patients with
      lesion crusting within 3 days and with lesion healing within 7 days and 10 days
      were significantly greater in the C. nutans extract-treated group than the
      placebo group (p < 0.01). Pain scores were reduced more rapidly in the C. nutans
      extract-treated group than in the placebo group. There were no side effects of
      the study medication.

PMID- 8576676
TI  - Preliminary survey of anti-HTLV-I in northeastern-Thais.
AB  - The anti-HTLV-I prevalence was studied by particle agglutination technique (PA)
      in 2,609 samples including: 403 antenatal care women from Srinagarind Hospital,
      Faculty of Medicine, 342 high-risk sexually transmitted disease blood donors and
      1,864 randomly selected blood donors from the Blood Transfusion Centre, Faculty
      of Medicine, Khon Kaen University. All of the 2,609 samples gave negative anti
      HTLV-I. The result revealed that HTLV-I infection is not common in northeast
      Thailand. However, as the sample size from this study may be too small, further
      study should be carried out.

PMID- 8576677
TI  - Angiolipoma of suprasellar region.
AB  - An angiolipoma of the suprasellar region occurred in an 8-year-old boy. Review of
      5 intracranial angiolipomas, including the current case, revealed that four were
      in the sellar region of one man and three women. One was in the thalamus of a
      man. The average age of the patients was 49 years, and average size of the tumors
      was 2.5 cm across. The angiolipomas associated with the sellar region often
      created abnormalities of the eye viz exophthalmos, decreased vision, and palsy of
      the oculomotor nerve. Sudden onset has ensued in a massively hemorrhagic thalamic
      angiolipoma. The characteristic low density with negative Hounsfield unit values
      in CT scan and hyperdensity in MRI of the brain suggested adipose tissue
      component of the angiolipoma. The angiography has depicted the angiomatous
      component of the latter. The combined characteristic CT scan, MRI, and
      angiographic features should demonstrate both vascular and adipose tissue
      elements of the angiolipomas before pathologic examination.

PMID- 8576678
TI  - Mucin-producing malignant meningioma with papillary and glandular patterns.
AB  - An exceedingly rare intracranial malignant meningioma with papillary and
      glandular patterns in a 45-year-old man is described. Intracellular mucin
      production was demonstrated. The nature of the neoplastic cells was verified by
      immunohistochemical and electron microscopic studies.

PMID- 8576679
TI  - Haemoglobin function in intact lamprey erythrocytes: interactions with membrane
      function in the regulation of gas transport and acid-base balance.
AB  - Haemoglobin function within lamprey erythrocytes offers a unique solution to gas
      transport among vertebrates. Lamprey haemoglobin within intact erythrocytes is in
      oligomer/monomer equilibrium and has an oxygen affinity similar to that of
      haemoglobin in other active fishes. The cooperativity of oxygen binding, which is
      reduced at low pH values, the effect of protons and the effect of the
      concentration of haemoglobin on its oxygen affinity are all due to
      dissociation/association reactions of the haemoglobin molecules. The permeability
      of the lamprey red cell membrane to acid and base equivalents is very low, and
      plasma bicarbonate cannot therefore be dehydrated to carbon dioxide to any
      significant extent during the residence time of blood in the gills. This
      potential limitation on carbon dioxide excretion is overcome, however, by the
      high intraerythrocytic pH and the marked oxygenation-linked pH changes in the
      erythrocyte, which are due to the large Haldane effect of the haemoglobin. Owing
      to the relative impermeability of the erythrocyte membrane to acid equivalents,
      intraerythrocytic haemoglobin cannot take part in the acid-base buffering of the
      extracellular compartment. As a consequence, extracellular acid loads cause
      marked fluctuations in plasma pH.

PMID- 8576680
TI  - Matrix of neuromodulators in neurosecretory structures of the crab Cancer
      borealis.
AB  - The crustacean stomatogastric ganglion, which is situated in the ophthalmic
      artery, can be modulated by both intrinsically released molecules and hormones.
      In the crab Cancer borealis, over a dozen neuroactive compounds have been
      identified in the input axons that project into the stomatogastric neuropil.
      However, little is known about the modulator content of the two major neurohemal
      organs, the sinus glands and the pericardial organs, in this crab. We now report
      the results of a series of immunocytochemical experiments designed to identify
      putative neurohormones in these tissues. We find that the majority of modulators
      present in the input axons of the stomatogastric ganglion are also present in at
      least one of the neurohemal organs. Specifically, allatostatin-like, buccalin
      like, cholecystokinin-like, FLRFamide-like, GABA-like, locustatachykinin-like,
      myomodulin-like, proctolin-like, red pigment concentrating hormone-like and
      serotonin-like immunoreactivities are all present in both the stomatogastric
      neuropil and at least one of the neurohemal organs. Thus, these substances are
      likely to serve a dual role as both local and hormonal modulators of the
      stomatogastric network. Two other substances, beta-pigment dispersing hormone and
      crustacean cardioactive peptide, are not present in the stomatogastric neuropil,
      but beta-pigment dispersing hormone immunoreactivity is present in the sinus
      glands and crustacean cardioactive peptide immunoreactivity is present in the
      pericardial organs. It is likely that crustacean cardioactive peptide exerts its
      influence on the stomatogastric neural circuit via hormonal pathways. Double
      labeling experiments show that the patterns of modulator co-localization present
      in the stomatogastric neuropil are different from those in the neurosecretory
      organs, suggesting that few rules of colocalization hold across these tissues.

PMID- 8576681
TI  - The length dependence of work production in rat papillary muscles in vitro.
AB  - The influence of length on work production was investigated for rat papillary
      muscles using the work loop technique. Active and passive length-force
      relationships were first determined under isometric conditions and the length for
      maximum force production (Lmax) was derived. Starting from different lengths
      within the physiological range, a series of work loops was generated using the
      stimulation phase shift, strain amplitude and cycle frequency previously found to
      be optimal for power output at 37 degrees C. The relationship between muscle
      length and net work was used to determine the length at which work output was
      maximal (Lopt). In order to examine the dynamic passive properties of the
      muscles, unstimulated muscles were subjected to the same regime of sinusoidal
      oscillation as used for the active loops. From the hysteresis loops, lengthening
      work (work done to extend the passive muscle), passive shortening work (work
      returned during shortening) and net energy loss (hysteresis) could be measured.
      The decline in net work production at lengths greater than 95% Lmax could largely
      be attributed to the rapid and non-linear increase in muscle stiffness and the
      increase in net energy loss over this range of lengths. The physiological
      significance of the length-work relationship is considered and the mechanical
      properties of active and passive papillary muscles are discussed with reference
      to sarcomere length and cardiac muscle ultrastructure.

PMID- 8576682
TI  - Distribution and action of SALMFamide neuropeptides in the starfish Asterias
      rubens.
AB  - The SALMFamides S1 and S2 are two structurally related neuropeptides that are
      present in starfish, and which share the C-terminal amino acid sequence
      SXLXFamide, where X is variable. To establish the distribution of S1 and S2 in
      starfish, we have raised antisera that recognise specifically the C-terminal
      pentapeptide sequence of either S1 or S2. Here we describe the production and
      characterisation of an S2-specific antiserum designated CLII. This antiserum,
      together with an S1-specific antiserum (BLII), has been used in a
      radioimmunoassay to measure S1 and S2 levels in extracts of body parts from the
      starfish Asterias rubens. High concentrations (250-400 pmol g-1) of both peptides
      were detected in the radial nerve cords of the nervous system and lower
      concentrations were detected in other body parts, including neuromuscular organs
      such as the tube feet, apical muscle and cardiac stomach. We have examined the
      pharmacological effects of S1 and S2 on the contractility of these three
      preparations. Neither S1 nor S2 influenced the tone of tube foot and apical
      muscle preparations but S2 caused relaxation of cardiac stomach preparations,
      antagonising the contracting action of acetylcholine.

PMID- 8576683
TI  - Several forms of callitachykinins are distributed in the central nervous system
      and intestine of the blowfly Calliphora vomitoria.
AB  - We have examined the distribution of two tachykinin-related neuropeptides,
      callitachykinin I and II (CavTK-I and CavTK-II), isolated from whole-animal
      extracts of the blowfly Calliphora vomitoria. Extracts of dissected brains,
      thoracic-abdominal ganglia and midguts of adult blowflies and the entire central
      nervous system of larval flies were analysed by high performance liquid
      chromatography (HPLC) combined with enzyme-linked immunosorbent assay (ELISA) for
      the presence of CavTKs. To identify the two neuropeptides by HPLC, we used the
      retention times of synthetic CavTK-I and II as reference and detection with an
      antiserum raised to locustatachykinin II (shown here to recognise both CavTK-I
      and II). The brain contains only two immunoreactive components, and these have
      exactly the same retention times as CavTK-I and II. The thoracic-abdominal
      ganglia and midgut contain immunoreactive material eluting like CavTK-I and II as
      well as additional material eluting later. The larval central nervous system
      (CNS) contains material eluting like CavTK-I and II as well as a component that
      elutes earlier. We conclude that CavTK-I and II are present in all assayed
      tissues and that additional, hitherto uncharacterised, forms of tachykinin
      immunoreactive material may be present in the body ganglia and midgut as well as
      in the larval CNS. An antiserum was raised to CavTK-II for immunocytochemistry.
      This antiserum, which was found to be specific for CavTK-II in ELISA, labelled
      all the neurones and midgut endocrine cells previously shown to react with the
      less selective locustatachykinin antisera. It is not clear, however, whether
      CavTK-I and II are colocalised in all LomTK-immunoreactive cells since there is
      no unambiguous probe for CavTK-I.

PMID- 8576684
TI  - Crustacean cardioexcitatory peptides may inhibit the heart in vivo.
AB  - Peptide neurohormones exist as functionally similar analogues in a wide variety
      of invertebrate and vertebrate phyla, and many have been implicated as
      cardiovascular regulators. In decapod crustaceans, these include the pentapeptide
      proctolin, crustacean cardioactive peptide (CCAP) and the FMRF amide-related
      peptides F1 and F2, all of which are found in the pericardial organs located
      immediately upstream of the heart. Cardioexcitatory activity has been
      demonstrated by these four peptides in both isolated and semi-isolated arthropod
      hearts; CCAP, however, has minimal effects on the heart of Cancer magister. In
      the present study, we determined the effects of proctolin, F1 and F2 on the heart
      of the crab C. magister in both in vitro (semi-isolated heart) and in vivo (whole
      animal) preparations. In semi-isolated hearts, infusion of each peptide caused
      cardioexcitation, increasing the rate and stroke volume of the heart. In whole
      crabs, the peptides were cardioinhibitory; the strongest effects were observed
      with F1 and F2, which dramatically decreased heart rate, cardiac stroke volume
      and cardiac output. These results cast doubt on current perceptions of the
      functional role of cardioactive peptides in the regulation of invertebrate
      cardiovascular performance in vivo.

PMID- 8576685
TI  - Ultrasound acoustic startle response in scarab beetles.
AB  - We discovered an auditory sense in a night-flying scarab beetle, Euetheola
      humilis, the first scarab to be shown to hear airborne sounds. In the field,
      beetles were captured beneath speakers broadcasting ultrasound that simulated bat
      echolocation pulses. Apparently, the beetles took evasive action from a potential
      bat predator and flew into the traps. Using another behavioral assay in
      laboratory studies, the beetles were sensitive to frequencies ranging from 20 to
      70 kHz at levels between 60 and 70 dB SPL. One component of the behavioral
      response, a head roll, was graded with stimulus intensity, and the number of
      potentials in electromyographic recordings from muscles involved in the roll
      increased as stimulus intensity increased. The response latency was about 40 ms
      at threshold, decreasing to about 30 ms at 20 dB above threshold. The beetle's
      short response latency is ideally suited for predator avoidance behavior and the
      frequency tuning of the response suggests that it could function in evasion from
      insectivorous bats. The beetle's acoustic sensitivity is remarkably similar to
      that of other night-flying insects showing ultrasound-induced startle and it
      should provide these scarab beetles with a similar advance warning of predation
      risk.

PMID- 8576686
TI  - A novel proline, glycine: K+ symporter in midgut brush-border membrane vesicles
      from larval Manduca sexta.
AB  - Alkali-cation-dependent uptake of proline and glycine into brush-border membrane
      vesicles from the midgut of the larval tobacco hornworm Manduca sexta was
      investigated using rapid filtration assays. Uptake of both amino acids was by
      electrophoretic symport, with K+ being the favored cation at pH 10. Counterflow
      accumulation of proline was elicited by glycine and vice versa, suggesting that
      the two amino acids are transported by a common symporter, which we designate the
      pro, gly: K+ symporter. L-alpha-Aminoisobutyric acid was the only other amino
      acid that elicited the accumulation of both proline and glycine. D-Proline was
      not symported; L-proline, glycine and L-alpha-aminoisobutyric acid appear to be
      the only substrates of the pro, gly: K+ symporter. Neutral amino acids with
      relatively short sidechains elicit glycine accumulation, suggesting that glycine
      may also be symported by the well-established neutral amino acid system. Since
      proline does not utilize the broad-spectrum, neutral system, its symport appears
      to be exclusively through the pro, gly: K+ symporter. Proline symport was found
      mainly in posterior midgut vesicles, suggesting that the pro, gly: K+ symporter
      may be localized in this region of the midgut.

PMID- 8576687
TI  - Immunolocalization of the 17 kDa vacuolar H(+)-ATPase subunit c in Heliothis
      virescens midgut and malpighian tubules with an anti-peptide antibody.
AB  - The transmembrane sector of V-ATPases is involved in proton conduction across the
      membrane where a 15-17 kDa proteolipid forms a putative proton channel. An
      affinity-purified rabbit polyclonal antibody was developed to an antigenic and
      putatively extracellular region of a cloned 17 kDa proteolipid. In larval tissue
      sections, this antibody labeled the midgut goblet cell apical membrane in
      Heliothis virescens (Lepidoptera: Noctuidae) and the apical membrane in
      Malpighian tubules from H. virescens and Manduca sexta (Lepidoptera: Sphingidae).
      The antibody also recognized the 17 kDa protein in an immunoblot of H. virescens
      Malpighian tubule homogenate. Northern blot analysis revealed the presence of two
      transcript sizes in the midgut (1.9 and 1.2 kb) and Malpighian tubules (2.2 and
      1.9 kb). Our results strongly support the hypothesis that the 17 kDa protein is a
      component of the V-ATPase, where it is thought to be the proton-conducting
      subunit. This polyclonal antibody may provide a powerful tool for V-ATPase
      regulation studies, while the use of the anti-peptide antibody approach may be
      helpful for the immunolocalization of other ductins.

PMID- 8576688
TI  - Dye coupling in the muscles controlling squid chromatophore expansion.
AB  - Dye coupling between the cone-shaped radial muscle fibres, which control the
      expansion and closing of a squid chromatophore organ, was investigated in the
      squid Loligo vulgaris. Particular attention was paid to the role of the
      myomuscular junctions located between the muscle fibres. Lucifer Yellow was
      injected ionophoretically into single muscle fibres under normal artificial sea
      water (ASW) and under various concentrations of calcium in ASW. Under ASW, 44% of
      muscle fibres examined were dye-coupled, 82% were coupled under calcium-free sea
      water and 67% were coupled under sea water containing high concentrations of
      calcium. Dye transfer was blocked by octanol. Muscle fibres were never seen to
      link adjacent chromatophore organs. Results are discussed in terms of the role of
      the myomuscular junctions in the regulation of chromatophore expansion in the
      living animal.

PMID- 8576689
TI  - Deciphering the hippocampal polyglot: the hippocampus as a path integration
      system.
AB  - Hippocampal 'place' cells and the head-direction cells of the dorsal presubiculum
      and related neocortical and thalamic areas appear to be part of a preconfigured
      network that generates an abstract internal representation of two-dimensional
      space whose metric is self-motion. It appears that viewpoint-specific visual
      information (e.g. landmarks) becomes secondarily bound to this structure by
      associative learning. These associations between landmarks and the preconfigured
      path integrator serve to set the origin for path integration and to correct for
      cumulative error. In the absence of familiar landmarks, or in darkness without a
      prior spatial reference, the system appears to adopt an initial reference for
      path integration independently of external cues. A hypothesis of how the path
      integration system may operate at the neuronal level is proposed.

PMID- 8576690
TI  - Sexually dimorphic spatial learning in meadow voles Microtus pennsylvanicus and
      deer mice Peromyscus maniculatus.
AB  - A number of studies examining developmental, neural and hormonal aspects of
      sexually dimorphic spatial learning (Morris water-maze) in meadow voles (Microtus
      pennsylvanicus) and deer mice (Peromyscus maniculatus) are described. We found
      that, in adult deer mice, female spatial performance decreased during the
      breeding season relative to the non-breeding season, whereas the reverse pattern
      was observed in male performance. There was a sex difference favouring males in
      spatial learning during the breeding season, but not during the non-breeding
      season. In adult meadow voles, females with low levels of oestradiol and males
      performed better in the water-maze than females with high levels of oestradiol.
      Postweaning voles (20 and 25 days after birth) acquired the water-maze task more
      quickly than preweaning voles (day 10). No sex difference in water-maze
      performance was evident at any of these juvenile ages. When these same voles were
      tested again as adults to investigate retention and re-acquisition of the water
      maze, both males and females from male-biased litters re-acquired the task better
      than males and females from female-biased litters. Together, the results of these
      studies indicate that sexually dimorphic spatial ability is dependent on the
      organization (in utero) and activational effects of gonadal hormones. These
      studies provide the first demonstration of the influence of natural changes in
      reproductive status on spatial learning of deer mice and meadow voles. The
      results also demonstrate that spatial performance of males and females is
      differentially affected by changes in reproductive status and that group
      differences in the laboratory are associated with group differences in space
      utilization in the wild. These findings help to clarify previous apparently
      contradictory findings about sex differences in spatial ability.

PMID- 8576691
TI  - Path integration in mammals and its interaction with visual landmarks.
AB  - During locomotion, mammals update their position with respect to a fixed point of
      reference, such as their point of departure, by processing inertial cues,
      proprioceptive feedback and stored motor commands generated during locomotion.
      This so-called path integration system (dead reckoning) allows the animal to
      return to its home, or to a familiar feeding place, even when external cues are
      absent or novel. However, without the use of external cues, the path integration
      process leads to rapid accumulation of errors involving both the direction and
      distance of the goal. Therefore, even nocturnal species such as hamsters and mice
      rely more on previously learned visual references than on the path integration
      system when the two types of information are in conflict. Recent studies
      investigate the extent to which path integration and familiar visual cues
      cooperate to optimize the navigational performance.

PMID- 8576692
TI  - Computations on metric maps in mammals: getting oriented and choosing a multi
      destination route.
AB  - The capacity to construct a cognitive map is hypothesized to rest on two
      foundations: (1) dead reckoning (path integration); (2) the perception of the
      direction and distance of terrain features relative to the animal. A map may be
      constructed by combining these two sources of positional information, with the
      result that the positions of all terrain features are represented in the
      coordinate framework used for dead reckoning. When animals need to become
      reoriented in a mapped space, results from rats and human toddlers indicate that
      they focus exclusively on the shape of the perceived environment, ignoring non
      geometric features such as surface colors. As a result, in a rectangular space,
      they are misoriented half the time even when the two ends of the space differ
      strikingly in their appearance. In searching for a hidden object after becoming
      reoriented, both kinds of subjects search on the basis of the object's mapped
      position in the space rather than on the basis of its relationship to a goal sign
      (e.g. a distinctive container or nearby marker), even though they have
      demonstrably noted the relationship between the goal and the goal sign. When
      choosing a multidestination foraging route, vervet monkeys look at least three
      destinations ahead, even though they are only capable of keeping a maximum of six
      destinations in mind at once.

PMID- 8576693
TI  - Do animals have cognitive maps?
AB  - Drawing on studies of humans, rodents, birds and arthropods, I show that
      'cognitive maps' have been used to describe a wide variety of spatial concepts.
      There are, however, two main definitions. One, sensu Tolman, O'Keefe and Nadel,
      is that a cognitive map is a powerful memory of landmarks which allows novel
      short-cutting to occur. The other, sensu Gallistel, is that a cognitive map is
      any representation of space held by an animal. Other definitions with quite
      different meanings are also summarised. I argue that no animal has been
      conclusively shown to have a cognitive map, sensu Tolman, O'Keefe and Nadel,
      because simpler explanations of the crucial novel short-cutting results are
      invariably possible. Owing to the repeated inability of experimenters to
      eliminate these simpler explanations over at least 15 years, and the confusion
      caused by the numerous contradictory definitions of a cognitive map, I argue that
      the cognitive map is no longer a useful hypothesis for elucidating the spatial
      behaviour of animals and that use of the term should be avoided.

PMID- 8576694
TI  - Peptidergic and adrenergic innervation of the lachrymal gland in the euryhaline
      turtle, Malaclemys terrapin.
AB  - The controlling factors of lachrymal gland secretions were examined in the
      euryhaline turtle, Malaclemys terrapin. Histochemical and immunocytochemical
      methods were used to localize some of the possible neurotransmitters involved.
      There was no immunoreactivity to choline acetyltransferase, the enzyme
      synthesizing acetylcholine, nor did the histochemical technique for
      acetylcholinesterase produce positive results. Immunofluorescence and
      immunoperoxidase labels revealed vasoactive intestinal peptide (VIP)- and
      neuropeptide Y (NPY)-like immunoreactivity in high concentrations surrounding the
      secretory tubules and ducts. Substance P produced a weak immunoreactivity in the
      interstitial space surrounding the ducts. Dopamine beta-hydroxylase, the enzyme
      synthesizing norepinephrine and epinephrine, was localized around the blood
      vessels. Immunogold labeling confirmed the presence of VIP- and NPY-like
      reactivity in nerve varicosities close to the basement membrane of the secretory
      epithelium, and double-labeling showed VIP and NPY are co-localized within the
      same nerve terminals. The results suggest that the secretory epithelium may be
      primarily under peptidergic control while the vascular system is under adrenergic
      control. This is possibly a new pattern of innervation for exocrine glands and
      may be related to the particular function of this salt gland in an euryhaline
      turtle.

PMID- 8576695
TI  - Proteins of crustacean exoskeleton: IV. Partial amino acid sequences of
      exoskeletal proteins from the Bermuda land crab, Gecarcinus lateralis, and
      comparisons to certain insect proteins.
AB  - As in all decapod Crustacea, the exoskeleton of the land crab Gecarcinus
      lateralis consists of four layers. Prior electrophoretic analysis of proteins
      extracted from these layers revealed an abundance of small M(r) proteins with
      acidic pIs are found in insect cuticle (O'Brien et al. [1991 Biol. Bull., 181:427
      441). Further, immunological cross-reactivity between crab exoskeletal proteins
      and insect cuticular proteins has been demonstrated (Kumari and Skinner [1993] J.
      Exp. Zool., 265:195-210). Partial amino acid sequences of a number of proteins
      from the four exoskeletal layers are described here. Proteins were
      electrophoresed on two-dimensional (2D) gels, transferred to polyvinylidene
      difluoride (PVDF) membranes, and stained; individual spots were recovered and
      their N-termini were sequenced. In addition, a 14-kDa protein (pI = 5.4) from
      membranous layer (ML14) was eluted from 2D gels and digested with endoproteinase
      Lys-C; N-termini of its constituent peptides were sequenced. The two epicuticular
      proteins differed from each other. Three proteins with identical electrophoretic
      mobility isolated from exocuticle, endocuticle, and membranous layer appeared to
      have identical N termini, while another electrophoretically identical set from
      the three layers appeared identical with each other but differed in three
      positions from the first set. Two proteins from the membranous layer both had a
      mass of 25 kDa but different isoelectric points. Their sequences were
      indistinguishable from each other but clearly distinct from another membranous
      layer protein. Another distinct sequence was found in a 14-kDa protein from
      endocuticle, while a less acidic pair of 14-kDa proteins from endocuticle and
      membranous layer were quite similar to one another. The three internal peptide
      fragments from ML14 were distinct, but one had regions similar to the ML14 N
      terminus. One crab exoskeletal protein sequence was similar to some structural
      proteins of vertebrates, whereas others had motifs found in insect cuticular
      proteins. The sequence similarities identified did not account for the antibody
      cross-reactivity.

PMID- 8576696
TI  - Development of cell polarity in budding yeast.

PMID- 8576697
TI  - Uptake of high-density lipoprotein by Y-organs of the crab Cancer antennarius:
      III. Evidence for adsorptive endocytosis and the absence of lysosomal processing.
AB  - Ecdysteroid hormones in crustaceans are synthesized from cholesterol in the Y
      organs. Circulating cholesterol is bound to high-density lipoprotein (HDL).
      Experiments were conducted to find the mode of cholesterol uptake by Y-organ
      cells. The working hypothesis is as follows: Cholesterol is taken up by
      endocytosis of the entire HDL-cholesterol complex. HDL was doubly labeled in the
      apolipoprotein and cholesterol components with 125I and 3H, respectively. The
      time courses of uptake of the two labels by Y-organ segments in vitro were
      parallel throughout 24 hr of incubation. Chloroquine, an inhibitor of lysosomal
      function, had no effect on the uptake and degradation of HDL. Cycloheximide, an
      inhibitor of protein synthesis, depressed HDL uptake. Transmission electron
      microscopy of Y-organ tissue showed features characteristic of adsorptive
      endocytosis, including coated pits in the plasma membranes and their invagination
      and vesiculation. Visualization of HDL with immunogold binding showed profiles
      consistent with endocytosis. Quantitation of the distribution of HDL-gold
      particles indicated that about 75% were associated with cellular formed elements,
      but not with lysosomes, and significantly more particles overall were present in
      cells from de-eyestalked crabs than those from intact crabs. These data
      demonstrate that (a) cholesterol-carrying HDL is taken into Y-organ cells by
      adsorptive endocytosis, (b) its uptake is dependent on de novo protein synthesis,
      (c) its intracellular processing is independent of lysosomal enzymes, and (d) its
      uptake is depressed by the molt-inhibiting hormone secreted by the eyestalks.

PMID- 8576698
TI  - The influence of optimization target selection on the structure of arterial tree
      models generated by constrained constructive optimization.
AB  - The computational method of constrained constructive optimization was used to
      generate complex arterial model trees by optimization with respect to a target
      function. Changing the target function also changes the tree structure obtained.
      For a parameterized family of target functions a series of trees was created,
      showing visually striking differences in structure that can also be quantified by
      appropriately chosen numerical indexes. Blood transport path length, pressure
      profile, and an index for relative segment orientation show clear dependencies on
      the optimization target, and the nature of changes can be explained on
      theoretical grounds. The main goal was to display, quantify, and explain the
      structural changes induced by different optimization target functions.

PMID- 8576699
TI  - Modification of inactivation in cardiac sodium channels: ionic current studies
      with Anthopleurin-A toxin.
AB  - The site 3 toxin, Anthopleurin-A (Ap-A), was used to modify inactivation of
      sodium channels in voltage-clamped single canine cardiac Purkinje cells at
      approximately 12 degrees C. Although Ap-A toxin markedly prolonged decay of
      sodium current (INa) in response to step depolarizations, there was only a minor
      hyperpolarizing shift by 2.5 +/- 1.7 mV (n = 13) of the half-point of the peak
      conductance-voltage relationship with a slight steepening of the relationship
      from -8.2 +/- 0.8 mV to -7.2 +/- 0.8 mV (n = 13). Increases in Gmax were
      dependent on the choice of cation used as a Na substitute intracellularly and
      ranged between 26 +/- 15% (Cs, n = 5) to 77 +/- 19% (TMA, n = 8). Associated with
      Ap-A toxin modification time to peak INa occurred later, but analysis of the time
      course INa at multiple potentials showed that the largest effects were on
      inactivation with only a small effect on activation. Consistent with little
      change in Na channel activation by Ap-A toxin, INa tail current relaxations at
      very negative potentials, where the dominant process of current relaxation is
      deactivation, were similar in control and after toxin modification. The time
      course of the development of inactivation after Ap-A toxin modification was
      dramatically prolonged at positive potentials where Na channels open. However, it
      was not prolonged after Ap-A toxin at negative potentials, where channels
      predominately inactivate directly from closed states. Steady state voltage
      dependent availability (h infinity or steady state inactivation), which
      predominately reflects the voltage dependence of closed-closed transitions
      equilibrating with closed-inactivated transitions was shifted in the depolarizing
      direction by only 1.9 +/- 0.8 mV (n = 8) after toxin modification. The slope
      factor changed from 7.2 +/- 0.8 to 9.9 +/- 0.9 mV (n = 8), consistent with a
      prolongation of inactivation from the open state of Ap-A toxin modified channels
      at more depolarized potentials. We conclude that Ap-A selectively modifies Na
      channel inactivation from the open state with little effect on channel activation
      or on inactivation from closed state(s).

PMID- 8576700
TI  - Voltage-dependent open-state inactivation of cardiac sodium channels: gating
      current studies with Anthopleurin-A toxin.
AB  - The gating charge and voltage dependence of the open state to the inactivated
      state (O-->I) transition was measured for the voltage-dependent mammalian cardiac
      Na channel. Using the site 3 toxin, Anthopleurin-A (Ap-A), which selectively
      modifies the O-->I transition (see Hanck, D. A., and M. F. Sheets. 1995. Journal
      of General Physiology. 106:601-616), we studied Na channel gating currents (Ig)
      in voltage-clamped single canine cardiac Purkinje cells at approximately 12
      degrees C. Comparison of Ig recorded in response to step depolarizations before
      and after modification by Ap-A toxin showed that toxin-modified gating currents
      decayed faster and had decreased initial amplitudes. The predominate change in
      the charge-voltage (Q-V) relationship was a reduction in gating charge at
      positive potentials such that Qmax was reduced by 33%, and the difference between
      charge measured in Ap-A toxin and in control represented the gating charge
      associated with Na channels undergoing inactivation by O-->I. By comparing the
      time course of channel activation (represented by the gating charge measured in
      Ap-A toxin) and gating charge associated with the O-->I transition (difference
      between control and Ap-A charge), the influence of activation on the time course
      of inactivation could be accounted for and the inherent voltage dependence of the
      O-->I transition determined. The O-->I transition for cardiac Na channels had a
      valence of 0.75 e-. The total charge of the cardiac voltage-gated Na channel was
      estimated to be 5 e-. Because charge is concentrated near the opening transition
      for this isoform of the channel, the time constant of the O-->I transition at 0
      mV could also be estimated (0.53 ms, approximately 12 degrees C). Prediction of
      the mean channel open time-voltage relationship based upon the magnitude and
      valence of the O-->C and O-->I rate constants from INa and Ig data matched data
      previously reported from single Na channel studies in heart at the same
      temperature.

PMID- 8576701
TI  - A molecular link between activation and inactivation of sodium channels.
AB  - A pair of tyrosine residues, located on the cytoplasmic linker between the third
      and fourth domains of human heart sodium channels, plays a critical role in the
      kinetics and voltage dependence of inactivation. Substitution of these residues
      by glutamine (Y1494Y1495/QQ), but not phenylalanine, nearly eliminates the
      voltage dependence of the inactivation time constant measured from the decay of
      macroscopic current after a depolarization. The voltage dependence of steady
      state inactivation and recovery from inactivation is also decreased in YY/QQ
      channels. A characteristic feature of the coupling between activation and
      inactivation in sodium channels is a delay in development of inactivation after a
      depolarization. Such a delay is seen in wild-type but is abbreviated in YY/QQ
      channels at -30 mV. The macroscopic kinetics of activation are faster and less
      voltage dependent in the mutant at voltages more negative than -20 mV.
      Deactivation kinetics, by contrast, are not significantly different between
      mutant and wild-type channels at voltages more negative than -70 mV. Single
      channel measurements show that the latencies for a channel to open after a
      depolarization are shorter and less voltage dependent in YY/QQ than in wild-type
      channels; however the peak open probability is not significantly affected in
      YY/QQ channels. These data demonstrate that rate constants involved in both
      activation and inactivation are altered in YY/QQ channels. These tyrosines are
      required for a normal coupling between activation voltage sensors and the
      inactivation gate. This coupling insures that the macroscopic inactivation rate
      is slow at negative voltages and accelerated at more positive voltages.
      Disruption of the coupling in YY/QQ alters the microscopic rates of both
      activation and inactivation.

PMID- 8576702
TI  - Effect of sarcoplasmic reticulum calcium depletion on intramembranous charge
      movement in frog cut muscle fibers.
AB  - Cut muscle fibers from Rana temporaria (sarcomere length, 3.3-3.5 microns;
      temperature, 13-16 degrees C) were mounted in a double Vaseline-gap chamber and
      equilibrated for at least an hour with an internal solution that contained 20 mM
      EGTA and phenol red and an external solution that contained predominantly TEA
      gluconate; both solutions were nominally Ca-free. The increase in total
      myoplasmic concentration of Ca (delta[CaT]) produced by sarcoplasmic reticulum
      (SR) Ca release was estimated from the change in pH produced when the released Ca
      was complexed by EGTA (Pape, P.C., D.-S. Jong, and W.K. Chandler. 1995. Journal
      of General Physiology. 106:259-336). The resting value of SR Ca content, [CaSR]R
      (expressed as myoplasmic concentration), was taken to be equal to the value of
      delta[CaT] obtained during a step depolarization (usually to -50 to -40 mV) that
      was sufficiently long (200-750 ms) to release all of the readily releasable Ca
      from the SR. In ten fibers, the first depolarization gave [CaSR]R = 839-1,698
      microM. Progressively smaller values were obtained with subsequent
      depolarizations until, after 30-40 depolarizations, the value of [CaSR]R had
      usually been reduced to < 10 microM. Measurements of intramembranous charge
      movement, Icm, showed that, as the value of [CaSR]R decreased, ON-OFF charge
      equality held and the amount of charge moved remained constant. ON Icm showed
      brief initial I beta components and prominent I gamma "humps", even after the
      value of [CaSR]R was < 10 microM. Although the amplitude of the hump component
      decreased during depletion, its duration increased in a manner that preserved the
      constancy of ON charge. In the depleted state, charge movement was steeply
      voltage dependent, with a mean value of 7.2 mV for the Boltzmann factor k. These
      and other results are not consistent with the idea that there is one type of
      charge, Q beta, and that I gamma is a movement of Q beta caused by SR Ca release,
      as proposed by Pizarro, Csernoch, Uribe, Rodriguez, and Rios (1991. Journal of
      General Physiology. 97:913-947). Rather, our results imply that Q beta and Q
      gamma represent either two distinct species of charge or two transitions with
      different properties of a single species of charge, and that SR Ca content or
      release or some related event alters the kinetics, but not the amount of Q gamma.
      Many of the properties of Q gamma, as well as the voltage dependence of the rate
      of SR Ca release for small depolarizations, are consistent with predictions from
      a simple model in which the voltage sensor for SR Ca release consists of four
      interacting charge movement particles.

PMID- 8576703
TI  - Estimation of the junctional resistance between electrically coupled receptor
      cells in Necturus taste buds.
AB  - Junctional resistance between coupled receptor cells in Necturus taste buds was
      estimated by modeling the results from single patch pipette voltage clamp studies
      on lingual slices. The membrane capacitance and input resistance of coupled taste
      receptor cells were measured to monitor electrical coupling and the results
      compared with those calculated by a simple model of electrically coupled taste
      cells. Coupled receptor cells were modeled by two identical receptor cells
      connected via a junctional resistance. On average, the junctional resistance was
      approximately 200-300 M omega. This was consistent with the electrophysiological
      recordings. A junctional resistance of 200-300 M omega is close to the threshold
      for Lucifer yellow dye-coupling detection (approximately 500 M omega). Therefore,
      the true extent of coupling in taste buds might be somewhat greater than that
      predicted from Lucifer yellow dye coupling. Due to the high input resistance of
      single taste receptor cells (> 1 G omega), a junctional resistance of 200-300 M
      omega assures a substantial electrical communication between coupled taste cells,
      suggesting that the electrical activity of coupled cells might be synchronized.

PMID- 8576704
TI  - Effect of arachidonic acid on activity of the apical K+ channel in the thick
      ascending limb of the rat kidney.
AB  - We have used patch-clamp techniques to study the effects of arachidonic acid (AA)
      on the activity of the 70-pS K+ channel, the predominant type of the two apical
      K+ channels operating under physiological conditions in the thick ascending limb
      (TAL) of the rat kidney. Addition of 5-10 microM AA blocked the activity of the
      70-pS K+ channel in both cell-attached and inside-out patches. The inhibitory
      effect of AA was specific, because application of 10 microM linoleic acid, oleic
      acid, or palmitic acid failed to mimic the effect of AA. The effect of AA could
      not be blocked by pretreatment of the TAL tubules with either 5 microM
      indomethacin (inhibitor of cyclooxygenase) or 4 microM cinnamyl-3,4-dihydroxy
      alpha-cyanocinnamate (CDC) (inhibitor of lipooxygenase). In contrast, addition of
      5 microM 17-octadecynoic acid (17-ODYA), an inhibitor of P450 monooxygenases,
      abolised the effect of AA on the channel activity, indicating that the effect was
      mediated by cytochrome P450 metabolites of AA. Addition of 10 nM 20
      hydroxyeicosatetraenoic acid (20-HETE), the main metabolite of the cytochrome
      P450 metabolic pathway in the medullary TAL, mimicked the inhibitory effect of 10
      microM AA. However, addition of 100 nM 19-HETE or 17-HETE had no significant
      effects and 100 nM 20-carboxy AA (20-COOH) reduced the channel activity by only
      20%, indicating that the inhibitory effect of 20-HETE was specific and
      responsible for the action of AA. Inhibition of the P450 metabolic pathway by
      either 5 microM 17-ODYA or 12, 12-dibromododec-11-enoic acid (DBDD) dramatically
      increased the channel activity by 280% in cell-attached patches. The stimulatory
      effect of 17-ODYA or DBDD was not observed in inside-out patches. The results
      strongly indicate that 20-HETE is a specific inhibitor for the 70-pS K+ channel
      and may play an important role in the regulation of the K+ channel activity in
      the TAL.

PMID- 8576705
TI  - Mechanism of K+ channel block by verapamil and related compounds in rat alveolar
      epithelial cells.
AB  - The mechanism by which the phenylalkylamines, verapamil and D600, and related
      compounds, block inactivating delayed rectifier K+ currents in rat alveolar
      epithelial cells, was investigated using whole-cell tight-seal recording. Block
      by phenylalkylamines added to the bath resembles state-dependent block of squid
      K+ channels by internally applied quarternary ammonium ions (Armstrong, C.M.
      1971. Journal of General Physiology. 58:413-437): open channels are blocked
      preferentially, increased [K+]o accelerates recovery from block, and recovery
      occurs mainly through the open state. Slow recovery from block is attributed to
      the existence of a blocked-inactivated state, because recovery was faster in
      three situations where recovery from inactivation is faster: (a) at high [K+]o,
      (b) at more negative potentials, and (c) in cells with type l K+ channels, which
      recover rapidly from inactivation. The block rate was used as a bioassay to
      reveal the effective concentration of drug at the block site. When external pH,
      pHo, was varied, block was much faster at pHo 10 than pHo 7.4, and very slow at
      pHo 4.5. The block rate was directly proportional to the concentration of neutral
      drug in the bath, suggesting that externally applied drug must enter the membrane
      in neutral form to reach the block site. High internal pH (pHi 10) reduced the
      apparent potency of externally applied phenylalkylamines, suggesting that the
      cationic form of these drugs blocks K+ channels at an internal site. The
      permanently charged analogue D890 blocked more potently when added to the pipette
      than to the bath. However, lowering pHi to 5.5 did not enhance block by external
      drug, and tertiary phenylalkylamines added to the pipette solution blocked
      weakly. This result can be explained if drug diffuses out of the cell faster than
      it is delivered from the pipette, the block site is reached preferentially via
      hydrophobic pathways, or both. Together, the data indicate the neutral membrane
      bound drug blocks K+ channels more potently than intracellular cationic drug.
      Neutral drug has rapid access to the receptor, where block is stabilized by
      protonation of the drug from the internal solution. In summary, externally
      applied phenylalkylamines block open or inactivated K+ channels by partitioning
      into the cell membrane in neutral form and are stabilized at the block site by
      protonation.

PMID- 8576706
TI  - Selenoprotein W of rat muscle binds glutathione and an unknown small molecular
      weight moiety.
AB  - When purified from rat muscle, selenoprotein W is fractionated into four forms
      distinguished by slightly different chromatographic behavior. Precise masses of
      the four forms were determined by matrix-assisted laser desorption/ionization
      (MALDI) time-of-flight mass spectrometry. The mass distribution of the forms
      (9549, 9592, 9853, and 9898 d) suggests that they occur through derivatization of
      the lowest mass form with two moieties of approximate masses 44 and 305 d. The
      apparent 305 d moiety was demonstrated to be glutathione (307 d) by reductive
      release from the 9853 d protein form with 1000-fold excess of dithiothreitol at
      50 degrees C. Milder conditions failed to remove the glutathione. The reduction
      produced nearly stoichiometric amounts of free glutathione as determined by HPLC
      of a fluorometric derivative. HPLC retention of the protein changed to match that
      of the 9549 d form, and a change of mass to 9550 d was observed by MALDI mass
      spectrometry. The identity of the 44 d moiety is unknown. The presence of
      glutathione in isolated selenoprotein W may suggest its involvement in the
      metabolism of this tripeptide.

PMID- 8576707
TI  - Ag(I)-binding to phytochelatins.
AB  - Phytochelatins (PCs) are glutathione-derived peptides with the general structure
      (gamma-Glu-Cys)nGly, where n varies from 2 to 11. A variety of metal ions such as
      Cu(II), Cd(II), Pb(II), Zn(II), and Ag(I) induce PC synthesis in plants and some
      yeasts. It has generally been assumed that the inducer metals also bind PCs.
      However, very little information is available on the binding of metals other than
      Cu(I) and Cd(II) to PCs. In this paper, we describe the Ag(I)-binding
      characteristics of PCs with the structure (gamma-Glu-Cys)2Gly, (gamma-Glu
      Cys)3Gly, and (gamma-Glu-Cys)4Gly. The Ag(I)-binding stoichiometries of these
      three peptides were determined by (i) UV/VIS spectrophotometry, (ii) luminescence
      spectroscopy at 77 K, and (iii) reverse-phase HPLC. The three techniques yielded
      similar results. ApoPCs exhibit featureless absorption in the 220-340 nm range.
      The binding of Ag(I) to PCs induced the appearance of specific absorption
      shoulders. The titration end point was indicated by the flattening of the
      characteristic absorption shoulders. Similarly, luminescence at 77 K due to Ag(I)
      thiolate clusters increased with the addition of graded Ag(I) equivalents. The
      luminescence declined when Ag(I) equivalents in excess of the saturating amounts
      were added to the peptides. At neutral pH, (gamma-Glu-Cys)2Gly, (gamma-Glu
      Cys)3Gly, and (gamma-Glu-Cys)4Gly bind 1.0, 1.5, and 4.0 equivalents of Ag(I),
      respectively. The Ag(I)-binding capacity of (gamma-Glu-Cys)2Gly and (gamma-Glu
      Cys)3Gly was increased at pH 5.0 and below so that Ag(I)/-SH ratio approached
      1.0. A similar pH-dependent binding of Ag(I) to glutathione was also observed.
      The increased Ag(I)-binding to PCs at lower pH is of physiological significance
      as these peptides accumulate in acidic vacuoles. We also report lifetime data on
      Ag(I)-PCs. The relatively long decay-times (approximately 0.1-0.3 msec)
      accompanied with a large Stokes shift in the emission band are indicative of spin
      forbidden phosphorescence.

PMID- 8576708
TI  - Cobalt(II), nickel(II), and copper(II) complexes of sulfanilamide derivatives:
      synthesis, spectroscopic studies, and antibacterial activity. Crystal structure
      of [Co(sulfacetamide)2(NCS)2].
AB  - The synthesis and characterization of new coordination compounds of Co(II),
      Ni(II), and Cu(II) with sulfacetamide (N-[4-(amino-fenil)sulfonil]acetamide) is
      reported. The complex [Co(sulfacetamide)2(NCS)2] crystallizes in the triclinic
      space group P-1. The cell dimensions are a = 7.80(2) A, b = 8.327(9) A, c =
      9.568(3) A, alpha = 90.5(1) degrees, beta = 90.5(1) degrees, gamma = 97.8(2)
      degrees, V = 616(1) A3, Z = 2, and Dx = 1.689 g/cm3. The final conventional R
      factor = 0.039 (Rw = 0.039) for 3535 "observed" reflections and 173 variables.
      The Co(II) is surrounded in a regular octahedral arrangement by two Nthyocianato
      from the NCS, two Namino and two Oacetamido atoms from the sulfacetamide. Each
      sulfacetamide, acting as a bidentate ligand, chelates two Co(II) ions as a bridge
      through the Namino and the Oacetamido atoms. IR, Reflectance Diffuse, EPR, and
      magnetic properties of the obtained complexes are discussed. The complexes were
      screened for their activity against E. Coli and S. aureus, showing an appreciable
      antimicrobial activity compared with the ligands.

PMID- 8576709
TI  - The interaction of antitumor-active anthraquinones with biologically important
      redox couples: I. Spectrophotometric investigation of the interaction of carminic
      acid and mitoxantrone with the iron (II, III) and copper (I, II) redox couples.
AB  - Studying the interaction of antitumor-active anthraquinones with biologically
      important redox couples is important in understanding the possible reductive or
      oxidative mode of metabolism of these antineoplastic agents coupled with the
      formation of free radicals. The interactions of such anthraquinones, i.e.,
      carminic acid (CA) and mitoxantrone (Mx) with iron(II, III) and copper(I, II)
      redox couples in oxygenated and deaerated solutions, were investigated by UV
      Visible and IR-spectroscopy. The superoxide radical reagent, nitroblue
      tetrazolium (NBT), was added to the metal and anthraquinone solutions and their
      binary mixtures at varying pH. Formazan, the reduction product of NBT, was
      produced mainly as a result of Fe(II)-NBT and Fe(II)-Mx-NBT interactions. The
      ternary mixtures of the lower valencies of iron and copper with CA and NBT
      exhibited intensive charge-transfer bands in the visible region, while metal-Mx
      NBT combinations did not produce such bands, possibly due to the blockage of the
      redox-active aminoethanolamine side-chains of Mx through coordination with the
      metals. Copper-Mx combinations showed an oxygen sensitivity as spectral evidence
      was obtained for the oxidative transformation of Mx to the cyclic primary
      metabolite. The results were evaluated in regard to the possible oxidative
      activation of the studied anthracenediones with iron and copper systems.

PMID- 8576710
TI  - Chemical heterogeneity in adult rat cerebellar Purkinje cells as revealed by
      zebrin I and low-affinity nerve growth factor receptor immunocytochemical
      expression following injury.
AB  - Cerebellar Purkinje cells in rat express low-affinity nerve growth factor
      receptor during development, but rarely in normal adult animals. However, after
      either mechanical injury or colchicine treatment during adulthood, these cells re
      express low-affinity nerve growth factor receptor-immunoreactive protein. Two
      Purkinje cell subpopulations were defined in normal adult cerebellum by the
      presence or the absence of zebrin I antigen. Nevertheless, it remains an open
      question as to whether low-affinity nerve growth factor receptor-immunoreactive
      protein can be expressed by all damaged Purkinje cells, independent of their
      location and their staining with antibodies against intrinsic molecular markers
      that reveal Purkinje cell heterogeneity, such as zebrin I. In this study, a
      serial-section immunocytochemical mapping of the expression zebrin I and low
      affinity nerve growth factor receptor, using specific monoclonal antibodies, we
      carried out in colchicine-treated rats. After mechanical damage of the cerebellar
      cortex, co-localization of these antigens at the cellular level was also analysed
      in thin adjacent sections, and by using a combined immunocytochemical staining
      method in individual sections. The findings revealed the existence of three sub
      sets of Purkinje cells: (1) two complementary groups distinctly immunoreactive to
      one antibody, but not to the other and (2) a third group that contained double
      labelled cells. In contrast, co-expression of both antigens was never observed
      following mechanical lesions. The seemingly independent response to mechanical
      injury of Purkinje cells located in different zebrin-defined compartments,
      indicates that particular subpopulations of Purkinje cells may respond
      differentially to traumatic injury.

PMID- 8576712
TI  - Transient co-localization of calretinin, parvalbumin, and calbindin-D28K in
      developing visual cortex of monkey.
AB  - This paper reports a double-labelling immunocytochemical study of the three
      calcium-binding proteins calretinin, parvalbumin, and calbindin-D28k in
      developing and adult Macaca primary visual cortex. In adult visual cortex, each
      protein marks a subset of GABAergic neurons with a characteristic laminar
      distribution and virtually no co-localization was found between these three
      proteins, suggesting that each calcium-binding protein may serve as a marker for
      one or more cortical subcircuits. The immature visual cortex, immunostained using
      identical techniques was then analysed to determine if each calcium-binding
      protein could serve as a developmental marker for these circuits. The Cajal
      Retzius cells of layer 1 contained all three proteins during development.
      Calbindin-D28k and calretinin were co-localized starting at Fd (foetal day) 45
      and after Fd125, parvalbumin also was present in the same Cajal-Retzius cells.
      All three proteins continued to be expressed until the Cajal-Retzius disappeared
      postnatally. In layers 2-6 calbindin-D28k and calretinin were never co-localized.
      In contrast, parvalbumin and calretinin were found in neurons of deep layer 3
      from Fd 155 to postnatal (P6) weeks with a few persisting even later. Before
      birth almost all PV+ neurons in layers 4-6 were CaB+, but by P3 weeks only a few
      PV+/CaB+ neurons remained in layer 4C and these completely disappeared by P6
      weeks. Co-localization in layer 4 neurons overlaps the period of ocular dominance
      segregation, suggesting that the onset of cortical maturity coincides with
      segregation of calcium-binding proteins within the GABA interneurons.

PMID- 8576711
TI  - Paranodal structural abnormalities in rat CNS myelin developing in vivo in the
      presence of implanted O1 hybridoma cells.
AB  - O1 hybridoma cells, which produce a monoclonal IgM antigalactocerebroside, were
      implanted into the spinal cords of immature and mature rats and the cords
      examined 5-24 days later. Study of the younger group, in which myelin was
      developing at the time of implantation, revealed examples of abnormal myelin
      sheaths in which the repeat period was markedly increased. The paranodal regions
      of these abnormal sheaths were superficially normal in configuration; i.e. myelin
      lamellae terminated one by one as 'terminal loops' that indented the axolemma and
      formed normal axoglial junctions displaying periodic 'transverse bands'.
      Neighbouring terminal loops are normally joined by tight junctions that block
      passage of tracers from the paranodal periaxonal space into the compact myelin,
      as seen after implantation of a control hybridoma. In the abnormal sheaths that
      developed after O1 implantation, in contrast, terminal loops were usually widely
      separated from each other. As a result, multiple pathways from the paranodal
      periaxonal space into the myelin sheath remained patent, forming potential routes
      for shunting nodal action currents. This subtle abnormality could thus compromise
      conduction, even though the sheaths might appear to be normally myelinated at the
      histological level. Equivalent abnormalities in human neurological diseases,
      including multiple sclerosis and paraproteinemic neuropathies, could underlie
      functional loss in the absence of frank demyelination.

PMID- 8576714
TI  - Monoclonal antibody markers for early development of the stereociliary bundles of
      mammalian hair cells.
AB  - Two monoclonal antibodies, SC1 and SC2, were raised in vitro against antigens
      from the stereocilia of guinea-pig hair cells. They both labelled stereociliary
      antigens that were not detected in any other cell within the cochlear duct or the
      vestibular epithelial. SC1 cross-reacted with the tectorial membrane in the
      cochlea and labelled both cochlear and vestibular hair cells from both the mouse
      and the rat. In the mouse the SC1 antigen was labelled from embryonic days 16-18,
      coincident with the development of the stereociliary bundles. SC1 cross-reacted
      with neuromuscular junctions from striated muscle and with basal keratinocytes in
      skin. SC2 did not cross-react cleanly with hair cells from the mouse or the rat
      but it cross-reacted with proximal tubules of the guinea-pig kidney. Both
      antibodies can be used as cellular markers within the guinea-pig cochlea and SC1
      should be particularly useful for studies of hair cell differentiation in the
      mouse.

PMID- 8576713
TI  - Ultrastructural identification of cholinergic neurons in the external cuneate
      nucleus of the gerbil: acetylcholinesterase histochemistry and choline
      acetyltransferase immunocytochemistry.
AB  - Using acetylcholinesterase histochemical and choline acetyltransferase
      immunocytochemical localization methods, this study has provided conclusive
      evidence for the existence of cholinergic neurons in the external cuneate nucleus
      of gerbils. By light microscopy, both acetylcholinesterase and choline
      acetyltransferase labelling was confined to the rostral portion of the external
      cuneate nucleus. Ultrastructurally, acetylcholinesterase reaction products were
      found in the nuclear envelope, cisternae of rough endoplasmic reticulum and Golgi
      saccules of some somata and large dendrites as well as in the membranes of small
      dendrites, myelinated axons and axon terminals. These neuronal elements were also
      stained for choline acetyltransferase; immunoreactivity was associated with
      nuclear pores, nuclear envelope, perikaryal membrane and all the membranous
      structures within the cytoplasm. Of the total choline acetyltransferase-labelled
      neuronal profiles analysed, 79% were myelinated axons, 15% dendrites, 4% somata
      and 2% axon terminals. The immunostained axon terminals consisted of two types
      containing either round (Rd type; 62.5%) or pleomorphic (Pd type; 37.5%)
      vesicles. Both were associated directly with choline acetyltransferase-positive
      dendrites. In contrast to the paucity of choline acetyltransferase-labelled axon
      terminals, numerous choline acetyltransferase-positive myelinated axons were
      present. It may thus be hypothesized that most, if not all, of the external
      cuneate nucleus cholinergic neurons are projection cells; such cells may give
      rise to axonal collaterals which synapse onto their own dendrites for possible
      feedback control. Choline acetyltransferase-positive dendrites were contacted by
      numerous unlabelled presynaptic boutons, 60% of which contained round or
      spherical synaptic vesicles (Rd boutons) and 40% flattened vesicles (Fd boutons),
      suggesting that these neurons are under strong inhibitory control. The
      preferential concentration of cholinergic components in the rostral external
      cuneate nucleus may be significant in the light of the highly organized
      somatotopy in the external cuneate nucleus and its extensive efferent projections
      to medullary autonomic-related nuclei. Our results suggest that the cholinergic
      neurons may be involved in somatoautonomic integration.

PMID- 8576715
TI  - Isolation and characterization of defective jimpy oligodendrocytes in culture.
AB  - This study characterizes jimpy oligodendrocyte-enriched secondary cultures
      isolated from 10-12 days in vitro primary glial cell cultures derived from 1-2
      day-old jimpy mouse brains. Proliferation of defective oligodendrocytes was
      carefully investigated with regard to the expression of myelin basic protein and
      proteolipid protein and their respective mRNAs. Less than 5% of contaminating
      astrocytes (GFAP+ cells) were usually present. The identity of jimpy
      oligodendrocytes was confirmed using an antibody directed against a peptide from
      the wild type proteolipid protein C-terminal sequence for immunocytochemistry and
      an oligonucleotide complementary to mRNA derived from exon 5 of the proteolipid
      protein gene for in situ hybridization. Both the antibody and the probe recognize
      only normal oligondedrocytes while jimpy oligodendrocytes always remain
      unstained. Proteolipid protein in normal and jimpy oligodendrocytes was detected
      with antibody recognizing normal and mutated forms. Between 80 and 95% of the
      cells in normal and jimpy cultures at 2 and 4 days in vitro in secondary cultures
      express myelin basic protein and proteolipid protein and their respective mRNAs.
      The percentage of oligodendrocytes (PLP+ or MBP+) in S phase of the cell cycle
      was 7-10% for both normal and jimpy oligodendrocytes. This contrasts with the in
      vivo situation where the proliferation rate of oligodendrocytes in jimpy brains
      is higher than in normal brains. In addition, jimpy oligodendrocytes remain
      unresponsive to basic fibroblast growth factor treatment while a similar
      treatment stimulates the proliferation of normal oligodendrocytes.

PMID- 8576716
TI  - 5'-nucleotidase activity as a synaptic marker of parasagittal compartmentation in
      the mouse cerebellum.
AB  - In the molecular layer of the mouse cerebellum, the histochemical activity of the
      adenosine-producing ectoenzyme 5'-nucleotidase discloses a parasagittal pattern
      of alternating enzyme-rich and enzyme-poor bands. In the rat, 5'-nucleotidase
      activity transiently labels cerebellar synapses during postnatal development and
      shifts later on towards an exclusive glial location in the molecular layer. We
      therefore asked whether different ultrastructural expression of 5'-nucleotidase
      would account for the light microscopic pattern seen in the adult mouse
      cerebellum. Using an enzyme cytochemical method, we localized 5'-nucleotidase
      activity on the glial cells and at the main types of asymmetrical synapses in the
      developing and mature cerebellum of the mouse. The percentage of labelled
      synapses increased until adulthood within the 5'-nucleotidase-positive bands.
      Here, the vast majority (86%) of the synapses were labelled against only 27%
      within the negative bands in the adult. Thus, 5'-nucleotidase appears as a marker
      of glia and of Purkinje cell synapses across cerebellar compartments. Changes in
      purinergic neuromodulation and/or cell adhesion mediated by 5'-nucleotidase
      across bands might participate in the functional differentiation of the
      cerebellar parasagittal subsets.

PMID- 8576717
TI  - Rebreathing improves accuracy of ventilatory monitoring.
AB  - OBJECTIVE: Our objective was to determine if rebreathing would reduce the
      gradient between arterial and end-tidal CO2 tension during positive-pressure
      ventilation. METHODS:  DESIGN: Experimental investigation. SETTING:
      Anesthesiology laboratory. SUBJECTS: A total of 10 dogs of either sex.
      INTERVENTIONS: Anesthesia (sodium pentobarbital) and muscle relaxation
      (pancuronium) were induced and animals were tracheally intubated and ventilated
      with a standard anesthesia ventilator and breathing circuit with CO2 absorber and
      then with a Mapleson D circuit with a fresh gas flow rate (VF) equal to alveolar
      ventilation plus the sampling flow rate of two capnometers. Rebreathing was
      varied by adjusting the respiratory rate (RR) so that minute ventilation (VE) to
      VF ratio was 1:1, 2:1, 3:1, and 4:1. RESULTS: CO2 production (ATPD) was
      determined as the product of expired concentration of CO2 and VE (BTPS). Alveolar
      ventilation (VA) was calculated by dividing the product of CO2 production and
      barometric pressure corrected for ambient temperature and water vapor pressure at
      body temperature by PaCO2. Tidal volume, RR, airway gas temperature,
      concentration of CO2 in gas at the tracheal tube and inlet/outlet of the
      mechanical ventilator, body temperature, arterial gas tensions and pH, heart
      rate, arterial blood pressure, and cardiac output were measured. Minute
      ventilation, mean arterial blood pressure and end-expiratory CO2 tension (PECO2)
      (BTPS) were calculated. During positive-pressure ventilation, concentration of
      inspired CO2 was zero with standard circuitry, and significantly increased with
      Mapleson D when VE:VF ratio was 1:1 (0.56 +/- 0.19%), 2:1 (1.97 +/- 1.30%), 3:1
      (2.56 +/- 1.05%), and 4:1 (3.01 +/- 1.45%) (p < 0.05). PECO2 was 34.8 +/- 3.2 mm
      Hg during ventilation with the standard circuit, and significantly increased
      during ventilation with Mapleson D when VE:VF ratio was increased from 1:1 (35.4
      +/- 2.5 mm Hg) to 2:1 (40.2 +/- 3.6 mm Hg) and was not further increased at a
      VE:VF ratio of 3:1 (41.8 +/- 2.7 mm Hg) or 4:1 (41.3 +/- 2.4 mm Hg). The selected
      fresh gas flow rate was appropriate, because PaCO2 remained unchanged regardless
      of VE:VF ratio, indicating PaCO2 was dependent on VF, not on VE. The gradient
      between PaCO2 and PECO2 during ventilation with the standard circuit was 6.6 +/-
      3.0 mm Hg; during ventilation with Mapleson D, it decreased significantly when
      VE:VF ratio was increased from 1:1 (6.5 +/- 3.6 mm Hg) to 2:1 (2.9 +/- 1.5 mm
      Hg), but was not significantly reduced further at 3:1 (1.7 +/- 1.1 mm Hg) or 4:1
      (1.8 +/- 0.5 mm Hg) (p < 0.05). CONCLUSIONS: Rebreathing with a Mapleson D
      circuit and a VF equal to VA permitted normal CO2 elimination. Arterial PCO2 to
      PECO2 gradient decreased significantly during rebreathing, thus improving the
      reliability of capnography for estimating arterial PCO2. Consideration should be
      given to using the Mapleson D as a rebreathing circuit.

PMID- 8576718
TI  - "Helper:" A critical events prompter for unexpected emergencies.
AB  - OBJECTIVE: The medical practitioner is faced with an increasing list of protocols
      and algorithms related to patient care. These recommendations are often difficult
      to recall, particularly in stressful emergency situations. Using advanced cardiac
      life support (ACLS) protocols, we built a computer-based system to exhibit
      precompiled response plans for medical emergencies. To validate the usefulness of
      this prompting device, we tested application of two of the nine ACLS algorithms,
      pulseless ventricular fibrillation/ventricular tachycardia (Vfib/Vtach) and
      bradycardia, in a simulated operating room (OR) environment. METHODS: The system
      utilized the software authoring system IconAuthor (Aimtec Inc., Nashua, NH) and a
      touch-screen monitor (DiamondScan, Microtouch, Methuen, MA). Prior to testing our
      system, all 39 subjects were given time to familiarize themselves with its
      operation. Subsequently, all subjects were videotaped while managing a standard
      simulated anesthetic. During the anesthetic, the subjects were presented with two
      emergency scenarios, not viewed during the familiarization period. The
      electrocardiographic (EKG) signals for normal sinus rhythm, ventricular
      fibrillation, and second-degree heart block were presented. By random selection,
      the prompter was available to half of the subjects for help with arrhythmia
      management (experimental group), while to half it was not (control group).
      RESULTS: A total of 39 subjects completed the exercise. Use of the prompter
      enabled significantly more subjects to administer correct drugs and dosages
      during ventricular fibrillation. The correct lidocaine dose was chosen more often
      by the experimental group than by the control (p = 0.015); similarly MgSO4 was
      appropriately ordered more often in the experimental group (p = 0.003). During
      second-degree heart block, atropine was correctly followed with a dopamine
      infusion (p = 0.004), and epinephrine infusion was ordered for refractory
      bradycardia (p = 0.002) more often in the experimental than the control group.
      CONCLUSIONS: These data demonstrate the value of a prompting device at the
      anesthesia workstation. We foresee the use of such prompters in many areas of
      medicine.

PMID- 8576719
TI  - Respiratory monitoring during postoperative analgesia.
AB  - Respiratory monitoring, using a novel flow sensor based on an acoustic principle,
      has been investigated in 30 patients during postoperative analgesia. Each patient
      was subjected to monitoring and human observation for 8 hr. The study was
      performed by independent observers at three clinics. Significant correlation was
      noted between respiratory rate (RR) determined by the sensor and the observers.
      Recordings of respiratory duration index (RDI), breathing time intervals (BTIs)
      indicated high sensitivity of the instrument to respiratory depression and
      perturbations in the breathing rhythm. More than 800 apnea alarms were noted,
      using an alarm setting of 30 sec; 61% of the categorized alarms were noted by the
      observers as true apneas. From the recordings it was shown that the number of
      alarms can be reduced by a factor of four if the alarm setting is changed to 45
      sec. We conclude that the suggested technique, with slight modifications,
      provides adequate respiratory monitoring of patients during postoperative
      analgesia.

PMID- 8576721
TI  - Clinical evaluation of a method for automatic detection and removal of artifacts
      in auditory evoked potential monitoring.
AB  - OBJECTIVE: The objective of our study was to evaluate the method for detection
      and removal of artifacts in evoked potential monitoring described earlier by
      Cluitmans and colleagues in a clinical setting. METHODS: The method for detection
      and removal of artifacts by Cluitmans and colleagues is based on the assumption
      that a sweep of the recorded electroencephalogram (EEG) signal contains artifacts
      if one or more variables derived from the signal deviates strongly from the
      normal range of values. Once these normal ranges are defined, all future EEG
      recordings that are recorded under comparable circumstances can be automatically
      evaluated for artifacts by tracking when one or more signal variables falls
      outside the normal range. To assess the performance of this method in a clinical
      setting, recordings from a learning set were visually evaluated for artifacts.
      From the empirical distribution functions of the signal variables, the thresholds
      for automatic detection of artifacts were determined. The auditory evoked
      potential (AEP) waveforms resulting after automatic screening were compared with
      the waveforms obtained after visual evaluation of the raw signal combined with
      manual exclusion of signal periods containing artifacts. RESULTS: The quality of
      the resulting waveform was improved by our method of automatic detection and
      removal of artifacts in 97% of partly contaminated recordings. In only 2% of the
      recordings, automatic screening slightly degraded the resulting waveform.
      CONCLUSIONS: We conclude that the described method of automatic detection and
      removal of artifacts in AEP recordings effectively improves the quality of the
      resulting AEP waveform, without excessive rejection of artifact-free signal
      periods. The signal variables used in this method seem appropriate for
      distinguishing artifact-free signal periods from periods containing artifacts for
      the types of artifact that were studied.

PMID- 8576720
TI  - End-tidal oxygen concentration and pulse oximetry for monitoring oxygenation
      during intratracheal jet ventilation.
AB  - OBJECTIVE: In this study, we evaluated the usefulness of end-tidal oxygen
      monitoring during intratracheal jet ventilation (ITJV) for endolaryngeal laser
      surgery. METHODS: A total of 20 consecutive patients of both genders scheduled
      for endolaryngeal procedures under general anesthesia were studied. Inspiratory
      oxygen concentration and respiratory rate were varied, with patients serving as
      their own controls. Readings of pulse oximetry, airway oxygen, and carbon dioxide
      concentrations were recorded, and arterial blood samples for blood gas analysis
      were taken. RESULTS: At jet cycle rates of 20 cycles/min, end-tidal oxygen (ETO2)
      concentration indicated alveolar hypoxia 30 to 60 sec before hypoxemia was
      detected by pulse oximetry. Jet mixing of inspiratory and expiratory gas caused a
      larger difference between end-tidal and arterial gas concentrations than normally
      seen with conventional ventilation. Correlations between ETO2 concentrations,
      oxygen saturations, and arterial oxygen levels depended on respiratory rate and
      inspiratory oxygen concentration; correlations were stronger at low than at high
      inspiratory oxygen concentrations and stronger at low than at high respiratory
      rates. CONCLUSIONS: ETO2 concentration should be maintained well over 21% during
      ITJV to prevent alveolar and arterial hypoxia. Monitoring of respiratory oxygen
      concentrations at jet cycle rates of 20 cycles/min and less verifies safe oxygen
      levels during laser surgery, and confirms adequate alveolar oxygenation.

PMID- 8576722
TI  - Interference in a pulse oximeter from a nerve stimulator.

PMID- 8576723
TI  - Patient simulator identifies faulty H-cylinder.

PMID- 8576724
TI  - Transesophageal echocardiography and monitoring applications.
AB  - Transesophageal echocardiography (TEE) is a widely used cardiac imaging technique
      that provides the clinician with a view of the heart as seen from the esophagus
      or stomach. Rapid advances in TEE transducer technology, coupled with the low
      risk, semi-invasive nature of the procedure, have fueled its use for cardiac
      monitoring of surgical and critical care patients, in addition to diagnostic
      imaging. Many recent research studies have demonstrated the utility of TEE for
      direct, real-time evaluation of global and regional left ventricular function not
      achievable with current competing technologies at the bedside. As a result of
      these advantages, TEE has become an emerging tool in cardiac monitoring at many
      centers around the world.

PMID- 8576725
TI  - For routine postoperative oxygen administration in the PACU.

PMID- 8576726
TI  - Against routine postoperative oxygen administration in the PACU.

PMID- 8576727
TI  - Changing physicians' practice patterns.

PMID- 8576728
TI  - Do you know your MGVS? Or what do anesthesiologists know about their MGVS?

PMID- 8576729
TI  - Is it ok to read during OR cases?

PMID- 8576730
TI  - Is it ok to read during OR cases.

PMID- 8576732
TI  - Is it ok to read during OR cases?

PMID- 8576731
TI  - Is it ok to read during OR cases?

PMID- 8576733
TI  - Is it ok to read during OR cases?

PMID- 8576734
TI  - Is it ok to read during OR cases?

PMID- 8576735
TI  - Is it ok to read during OR cases?

PMID- 8576736
TI  - Part-time nursing faculty: suggestions for change.

PMID- 8576737
TI  - SPEAKING against student academic dishonesty: a communication model for nurse
      educators.

PMID- 8576738
TI  - Faculty workload and collegial support related to proportion of part-time faculty
      composition.
AB  - Part-time faculty use has become more prevalent in higher education in response
      to enrollment shifts and budgetary constraints. This descriptive, exploratory
      study used a mailed survey to investigate whether full-time nursing faculty
      perceptions of workload and collegial support differ with changes in the
      proportion of part-time faculty in Comprehensive I baccalaureate nursing
      programs. Workload was measured by Dick's Workload Instrument. Collegial support
      was measured by the Survey of Collegial Communication, adapted by Beyer, which
      was based on Likert's organizational model. Schools were partitioned into three
      strata based on the proportion of part-time faculty employed (low, medium, and
      high). A 30% sample of schools were randomly selected from each stratum (10
      schools from each). Within each selected school, six full-time undergraduate
      faculty were chosen by their respective deans to participate. The total response
      rate was 89.4%. The results of this study did not support assertions about part
      time faculty use in the literature and existing accreditation standards. Findings
      indicated that there were significant differences in reported total faculty
      workload when varying proportions of part-time faculty are employed. Faculty in
      nursing programs with medium proportions of part-time faculty reported higher
      average total workloads per week than faculty in programs with low and high
      proportions of part-timers. Another finding demonstrated that full-time faculty
      in nursing programs with high proportions of part-time faculty spend fewer hours
      in direct clinical supervision of their students when compared with faculty in
      the other two strata. There were, however, no differences in perceived collegial
      support among full-time faculty participants. It was recommended that further
      research be conducted to investigate specific workload differences found in this
      study using more precise quantitative measures. Communication and collegiality
      between part-time and full-time faculty should be further developed and
      researched under more controlled conditions. Case studies of arrangements that
      make part-time faculty use beneficial are needed. Other variables such as
      leadership style, scholarly productivity, and morale and their relationship to
      the proportion of part-time faculty employed in the nursing program should be
      investigated.

PMID- 8576739
TI  - Do clinical experiences affect nursing students' attitudes toward the elderly?
AB  - This descriptive study examined nursing students' attitudes toward the elderly
      pre- and post-clinical experiences in two healthcare settings (nursing home and
      hospital) and the relationship of knowledge about the elderly to student
      attitudes. Kogan's Attitude Toward Old People's Scale measured students'
      attitudes before and after their clinical experiences. In the same way, Palmore's
      Facts on Aging Quiz assessed the subjects' knowledge about the elderly. A
      Demographic Data Form collected information on selected variables and a Clinical
      Data Form collected information on subjects' clinical placement and the ages of
      their clients. The results of this study indicate that students' attitudes toward
      the elderly improved regardless of their clinical setting and that there was a
      positive relationship between knowledge and attitudes. This illustrates that
      faculty may need to be less concerned about the students' clinical setting and
      focus more on the addition of gerontological content in the nursing curriculum.

PMID- 8576741
TI  - Nursing students' opinions on interpersonal violence.
AB  - This study examines the opinions of professional nursing students toward
      interpersonal violence and compares their responses to published expert opinion.
      The subjects included all nursing students enrolled in a selected associate
      degree program. A questionnaire, consisting of 23 opinion statements and coded to
      the subject's semester level, was prepared and distributed by the nursing
      faculty. Using a four point Likert scale, the subjects indicated their intensity
      of agreement to these statements. Also included were two open-ended questions
      regarding tie cause and prevention of violence and several inquires of
      demographic relevance. Frequency distributions were applied to all the responses
      with further statistical analysis of specific variables done through one-way
      analysis of variance, T-test, and correlation studies. The results showed a
      remarkable congruency of student opinion although the variables of ethnicity,
      previous work experience, being a parent, having a college degree, and age were
      associated with certain opinion choices. This study suggests that contemporary
      students enter nursing programs with appreciable educational and work related
      experiences and at a sophisticated level in regard to cognizance about
      sociological issues. The author suggests that nursing educators not only make
      curricular revisions in theory content and its clinical application but also in
      teaching methodology.

PMID- 8576740
TI  - Evaluation of the Facts on Aging Quizzes I & II.
AB  - The Facts on Aging Quizzes (FAQ) I and II (Palmore, 1977, 1981) were designed to
      assess knowledge and to measure misconceptions regarding the elderly. This study
      compared results on the FAQ I and II administered to freshmen nursing students.
      In contrast with Palmore's (1981, 1988) findings, the FAQ I and II were not
      related (r=.04) and alpha coefficients were low (a=.45 and .32 respectively).
      However, use of theta coefficients (which make fewer stringent assumptions about
      items being parallel) resulted in values of .60 and .64 respectively. The factors
      emerging in this study differed from Palmore's (1977, 1981, 1988) conceptual
      structure and explained only 45% of the variance. Results from this study suggest
      that while the FAQ I and II may be useful as a stimulus for discussion, revisions
      and testing need to be done if they are to be used for research purposes.

PMID- 8576742
TI  - Sharing the wealth: collaboration on practice readiness.

PMID- 8576743
TI  - Introduction to nursing summer recruitment institute for high school juniors.

PMID- 8576744
TI  - The future of neonatology in the managed care era.

PMID- 8576745
TI  - Value of negative nose and ear cultures in identifying high-risk infants without
      early-onset group B streptococcal sepsis.
AB  - Initiation of antibiotic therapy shortly after birth in infants at high risk for
      early-onset group B streptococcal sepsis is a common practice. The purpose of the
      current study was to evaluate whether the absence of group B streptococcal
      isolation from nose or ear cultures in such infants would have a high negative
      predictive value and low false-negative rate in predicting infants without sepsis
      and therefore whether such cultures would be of value in determining in which
      infants antibiotics could be safely discontinued. Infants admitted to the
      neonatal intensive care unit during 1989 and 1990 had a nasal culture obtained at
      admission and during 1991 and 1992 had an ear canal culture. Infants in whom
      sepsis was suspected had a blood culture in addition to a complete blood cell
      count, urine latex agglutination study for group B streptococci antigen, chest
      roentgenography and frequent monitoring of physiologic variables. The negative
      predictive value of nose and ear was 99% (2144 of 2149) and the false-negative
      rate was 7% (five negative surface cultures from 72 infants with sepsis in whom
      surface cultures were obtained). All five false-negative cultures were obtained
      from the ear canal. The false-negative rate of nose cultures was 0% (0 of 35).
      The high negative predictive value and low false-negative rate of nose cultures
      in identifying infants without sepsis suggest that nose cultures may provide
      additional valuable information in identifying the infant in whom antibiotics may
      be safely discontinued in the absence of other factors suggestive of systemic
      infection.

PMID- 8576746
TI  - Renal calcification: a complication of dexamethasone therapy in preterm infants
      with bronchopulmonary dysplasia.
AB  - We have previously reported a case study in which renal calcification formation
      may have been a complication of dexamethasone exposure in an infant with
      bronchopulmonary dsyplasia. To determine whether dexamethasone is associated with
      renal calcification formation, we conducted a prospective, nonrandomized study of
      36 infants < 30 weeks' gestation and weighing < 1250 gm treated with
      dexamethasone because of bronchopulmonary dysplasia and compared them with a
      group not receiving dexamethasone. We identified seven infants in the
      dexamethasone group (n = 19) but no infant in the comparison group (n = 17) with
      renal calcifications at 2 months of age (p = 0.008). The urinary calcium
      excretion tended to be increased (15.5 +/- 16.6 vs 6.9 +/- 6.7 mg/kg/day ?p =
      0.05?) and the calcium/creatinine ratio was significantly greater in the
      dexamethasone group (1.2 +/- 1.0 vs 0.6 +/- 0.4 ?p = 0.02?). Infants who received
      dexamethasone were significantly smaller 819.1 +/- 141.1 vs 954.6 +/- 141 gm ?p =
      0.008?), were younger (26.2 +/- 1.7 vs 27.7 +/- 1.2 weeks ?p = 0.004?), received
      ventilator support longer (33.3 +/- 14.7 vs 12.1 +/- 14.7 days ?p = 0.0001?), and
      required more days of supplemental oxygen (54.3 +/- 9.7 vs 36.4 +/- 23.8 days ?p
      = 0.009?). We conclude that smaller, younger, and sicker infants are at the
      highest risk for the development of renal calcifications and that dexamethasone
      may be associated with increased urinary calcium excretion, which contributes to
      renal calcification formation.

PMID- 8576747
TI  - A trial of pulsatile versus continuous oxytocin administration for the induction
      of labor.
AB  - The objective of this study was to compare the efficacy and complications of
      intermittently pulsed oxytocin administration with continuous infusion in the
      induction of labor. Patients undergoing scheduled induction of labor at term were
      randomized to a pulsatile group in which oxytocin was infused in boluses every 8
      minutes or to a control group in which oxytocin was administered through a
      conventional continuous intravenous infusion. A total of 38 patients were
      studied. The groups were similar with respect to parity, gestational age,
      indication for induction, preinduction Bishop's score, and the use of
      prostaglandin gel for cervical ripening. The average induction-to-delivery
      interval was similar in both groups (14 hours). The frequency of uterine
      hyperstimulation was similar in both groups, as was the frequency of uterine of
      decreases in the rate of oxytocin infusion for any reason. The rate of cesarean
      delivery was similar (three in each group). The frequency of failed induction was
      similar with three in the pulsatile group and none in the continuous group.
      Pulsatile infusion of oxytocin was as efficacious as continuous infusion.
      However, it seems to offer no clinical advantage in this situation.

PMID- 8576748
TI  - The incidence of gastroesophageal reflux in preterm infants.
AB  - We observed an increased incidence of gastroesophageal reflux (GER) in a group of
      preterm infants. Seventy-five infants (birth weight 1117 +/- 242 gm, gestational
      age 30 +/- 3 weeks) were tested within 1 week before hospital discharge (37 to 38
      weeks postconceptional age). All of the infants had a two-channel
      pneumocardiogram and a 1-hour esophageal pH study (Tuttle test). Home monitors
      were used for all infants after hospital discharge and their use was maintained
      until standard discontinuation criteria were achieved. The Tuttle test was
      abnormal in 47 (63%) of the infants. Of the 47 infants with GER, 22 (47%) had
      evidence of obstructive apnea during the periods of reflux and 32 (68%) had an
      abnormal PCG result. Thirty-eight (81%) of the infants with GER had episodes of
      either obstructive or central apnea. The diagnosis of GER is important in
      premature infants because of the high association with recurrent or obstructive
      apnea.

PMID- 8576750
TI  - Direct calorimetry for the measurement of heat release in preterm infants:
      methods and applications.
AB  - Direct calorimetry is a sensitive and accurate method for the measurement of
      biologic heat release in humans. At the Children's Medical Center of Brooklyn,
      State University of New York, we have established direct calorimetry for the
      measurement of heat release by low birth weight premature infants. We have tested
      the method and find it to be simple, safe, and accurate. We studied heat release
      in 10 low birth weight infants on 22 occasions. The smallest infant in the study
      group weighed 1.43 kg. All the infant underwent direct calorimetry between 1 week
      and 18 weeks of age. Heat release in the infants ranged from 1.31 kcal/kg/hr.
      This method of direct calorimetry offers a tool for measuring total metabolic
      heat release from the first weeks of life in very low birth weight infants to
      estimate the insensible water losses and to examine the effect of various feeding
      regimens and disease states on total heat release.

PMID- 8576749
TI  - Martial status and military occupational specialty: neither factor has a
      selective adverse effect on pregnancy outcome.
AB  - This investigation was undertaken to determine whether there is a relationship
      between martial status or military occupational specialty (MOS) and pregnancy
      outcome in and active-duty population. In this prospective, descriptive study 312
      active-duty women were identified as married or single and stratified into four
      groups on the basis of MOS: group I (n = 144), mild to moderate mental stress;
      group II (n = 43), intensive mental stress; group III (n = 72), exposure to
      hazardous material; and group IV (n = 53), physical stress. Each patient group
      was evaluated to determine the incidence of medical complications. One hundred
      ninety-three of the service women were married and 70 were single. There was no
      significant difference between pregnancy complications and martial status. In
      spite of considerable stress and hazardous exposure the incidence of medical
      complications of pregnancy observed among groups (group I = 67%, group II = 58%,
      group III = 48% and group IV = 53%) was not significantly different. On the basis
      of the findings of this study we conclude that martial status and MOS did not
      significantly influence military pregnancy outcome.

PMID- 8576751
TI  - Accuracy and reliability of weight change determinations in a model infant
      weighing less than 750 grams.
AB  - We designed a study to address the accuracy and reliability of the weighing
      process for tiny infants ( < 750 gm). A model was made with intravenous bags and
      stockinette and the following equipment was added: umbilical artery and venous
      catheters, endotracheal tube, pulse oximeter probe, electrodes, and orgastric
      tube. The models weight was changed in intervals of 2 to 43 gm and it was then
      weighed on two different types of scales. The measured weight on each scale was
      compared with the predicted weight (calculated as initial + added mass), and the
      mean absolute difference (MAD) was determined. All measurements were obtained by
      the same two nurses. For the bedside scale the MAD was 5 gm (range - 23 to + 10;
      n = 30). Similar results were obtained with a sling scale; the MAD was 3 gm
      (range - 13 to + 6 n = 30). The range of differences noted suggests that
      discrepancies between measurements may lead to a difference between weights that
      is in the range of 4% to 7% body weight. Interobserver variability was noted to
      affect the reliability of the weight determinations. When five experienced
      neonatal intensive care units nurses weighed the model the MAD was 9 gm (-33 to +
      22; n = 15) and 6 gm (range - 11 to + 28; n = 15) for the bedside and sling
      scales, respectively. For the predicted weight, these discrepancies represent
      potential errors of 7.4% and 5.2%, respectively. These values are likely to
      underestimate the potential errors seen clinically inasmuch as we could not
      duplicate infant movement or anxiety of the person weighing the infant. These
      results should be considered when protocols are developed for weighing extremely
      small preterm infants.

PMID- 8576752
TI  - Hemidiaphragmatic paralysis as a complication of central venous catheterization
      in a neonate.
AB  - Central venous catheter placement has become commonplace in the care of the
      premature infant because of the need for long-term venous access. Although
      generally considered safe, there have been numerous reports of complications from
      the use of these catheters. We report the case of an infant in whom right
      hemidiaphragmatic paralysis developed after extravasation of fluid from a central
      venous catheter. The case emphasizes the need for continued vigilance of central
      venous catheter location and function.

PMID- 8576753
TI  - Neuroimaging in the high-risk infant: relationship to outcome.
AB  - Early brain development involves a genetically programmed, spatially organized,
      and temporally orchestrated cascade of events. Deleterious prenatal perinatal
      events may disrupt this sequence and lead to a spectrum of developmental
      impairments including cerebral palsy and mental retardation. Before the advent of
      cranial ultrasonography, cranial tomography, and magnetic resonance imaging,
      neuropathologic correlations were usually established post mortem. These
      neuroimaging modalities have improved the identification of brain lesions in
      surviving high-risk preterm and term infants. This has permitted inferences as to
      timing and pathophysiologic condition of the insult(s) and has facilitated
      correlations with clinical examination. In very low birth weight infants
      ultrasonographic abnormalities reflecting white matter damage have the strongest
      correlations with cerebral palsy: (1) persistent ventricular enlargement or
      persistent parenchymal echodensities carry a 50% risk for cerebral palsy, and (2)
      large bilateral cysts in periventricular white matter carry a risk approaching
      75% to 95%. In term infants neuroimaging studies show selective vulnerability in
      cerebral cortex and basal ganglia. This article reviews relationships between
      neuroimaging findings and outcome to help clinicians interpret the results and to
      gain an understanding of risk in their patients.

PMID- 8576754
TI  - Nasogastric intubation for nutrition and airway protection in infants with Robin
      sequence.
AB  - Airway obstruction and feeding difficulty associated with Robin sequence may be
      difficult management problems that require invasive therapeutic measures. We
      present two cases of infants with airway obstruction who were treated
      successfully as outpatients by placement of a nasogastric tube for airway
      maintenance and supplementation of oral feeding. In patients with Robin sequence
      who have upper airway obstruction and feeding difficulties not resolved by prone
      positioning, placement of an indwelling nasogastric tube should be considered
      before an invasive surgical procedure is undertaken.

PMID- 8576755
TI  - Ultrasonographic evaluation of birth injury to the shoulder.
AB  - Injuries of the proximal humerus in infants are often missed or misinterpreted
      because the humeral epiphysis is frequently nonossified. Ultrasonography enables
      direct visualization of the proximal humeral epiphysis, metaphysis, joint space,
      and relationship of the epiphysis with the glenoid cavity. We describe an infant
      with unexplained agitation and ventilatory difficulty related to a fracture of
      the proximal right humerus that was not appreciable on plain film radiographs.
      Sonographic imaging of the shoulder, with use of the opposite side for
      comparison, clearly demonstrated a Salter I proximal humeral fracture with marked
      metaphyseal displacement and preservation of the normal epiphyseal-glenoid
      relationship.

PMID- 8576756
TI  - The future of neonatology in the managed care era.

PMID- 8576757
TI  - Neonatology in a managed care environment.

PMID- 8576758
TI  - The future of neonatology in the managed care era.

PMID- 8576759
TI  - The "medical loss ratio": the determination of medical standards by the
      marketplace.

PMID- 8576760
TI  - Managing to find value.

PMID- 8576761
TI  - The future of neonatology in the managed care era.

PMID- 8576762
TI  - Perinatal services in the era of managed care: a Kaiser Permanente physician's
      perspective.
AB  - Evolving market forces are reshaping current patient, parent, provider, insurer,
      and hospital relationships. The traditional individualistic focus for
      accountability and responsibility is being supplemented by population-wide
      responsibilities and accountabilities. These changes, often lumped together as
      "managed care", are being implemented with evolving ideas on how best to manage
      an organize collaborative activity. In this article it is reasoned that perinatal
      services will improve as objective outcome measures guide the development,
      evolution, and operation of competing managed care networks. The article
      illustrates how a managed perinatal care network works with experiences drawn
      from the perinatal service programs of Kaiser Permanente's Southern California
      Region.

PMID- 8576763
TI  - Realities of a premature infant's first year: helping parents cope.

PMID- 8576764
TI  - Umbilical cord ulceration as a cause of hypoxic-ischemic encephalopathy: report
      of a case and review of the literature.
AB  - We report a case of hypoxic-ischemic injury caused by acute hemorrhage from an
      umbilical cord ulceration in a newborn infant with an antenatal diagnosis of
      small bowel obstruction. Recognition of the association between umbilical cord
      ulceration and small bowel obstruction may alter obstetric and delivery room
      management.

PMID- 8576766
TI  - Placental pathology casebook. Long umbilical cord with torsion and diffuse
      chorionic surface vein thrombosis: multiple associated congenital abnormalities
      including destructive encephalopathy.

PMID- 8576765
TI  - Antenatally diagnosed neonatal craniopharyngioma.
AB  - A case of neonatal craniopharyngioma diagnosed by fetal ultrasonography at 29
      weeks and by magnetic imaging at 35 weeks of gestation is presented with clinical
      and neuroradiologic findings. This is a rare tumor and only 10 cases of neonatal
      craniopharyngioma have been previously reported .

PMID- 8576767
TI  - Neonatal radiology casebook. Bronchopleural fistula and pneumothorax:
      complications of transpyloric feeding tube insertion.

PMID- 8576768
TI  - Special imaging casebook. Chiari II malformation.

PMID- 8576769
TI  - The test of functional health literacy in adults: a new instrument for measuring
      patients' literacy skills.
AB  - OBJECTIVE: To develop a valid, reliable instrument to measure the functional
      health literacy of patients. DESIGN: The Test of Functional Health Literacy in
      Adults (TOFHLA) was developed using actual hospital materials. The TOFHLA
      consists of a 50-item reading comprehension and 17-item numerical ability test,
      taking up to 22 minutes to administer. The TOFHLA, the Wide Range Achievement
      Test--Revised (WRAT-R), and the Rapid Estimate of Adult Literacy in Medicine
      (REALM) were administered for comparison. A Spanish version was also developed
      (TOFHLA-S). SETTING: Outpatient settings in two public teaching hospitals.
      PATIENTS: 256 English- and 249 Spanish-speaking patients were approached. 78% of
      the English- and 82% of the Spanish-speaking patients gave informed consent,
      completed a demographic survey, and took the TOFHLA or TOFHLA-S. RESULTS: The
      TOFHLA showed good correlation with the WRAT-R and the REALM (correlation
      coefficients 0.74 and 0.84, respectively). Only 52% of the English speakers
      completed more than 80% of the questions correctly. 15% of the patients could not
      read and interpret a prescription bottle with instructions to take one pill by
      mouth four times daily, 37% did not understand instructions to take a medication
      on an empty stomach, and 48% could not determine whether they were eligible for
      free care. CONCLUSIONS: The TOFHLA is a valid, reliable indicator of patient
      ability to read health-related materials. Data suggest that a high proportion of
      patients cannot perform basic reading tasks. Additional work is needed to
      determine the prevalence of functional health illiteracy and its effect on the
      health care experience.

PMID- 8576770
TI  - The impact of an ambulatory rotation on medical student interest in internal
      medicine. The Society of General Internal Medicine Task Force on Career Choice in
      Internal Medicine.
AB  - OBJECTIVE: To determine whether students who take ambulatory rotations in
      internal medicine are more likely to choose internal medicine careers. DESIGN:
      National survey. SETTING AND PARTICIPANTS: The intended sample was 1,650 senior
      U.S. medical students from 16 medical schools, of whom 1,244 (76%) responded.
      Representative schools nationwide were selected using a stratified, random
      sampling method. MEASUREMENTS: The questionnaire asked about characteristics of
      the ambulatory rotation, perceptions of internal medicine, and factors
      influencing students toward or away from an internal medicine career. RESULTS:
      Ambulatory rotations were taken by 543 students (43%). Of these rotations, 73%
      were required, 74% were during the fourth year, 77% were in general internal
      medicine, 73% provided continuity of care, and 19% were during the medicine
      clerkship. Overall, 24% of the students chose careers in general (9%) or
      subspecialty internal medicine (15%). Thirty percent of the students who did
      ambulatory rotations planned internal medicine careers, compared with 19% of the
      students who had no rotation [odds ratio (OR) = 1.8, 95% confidence interval (CI)
      1.3 to 2.4, p = 0.0001]. This association was of similar magnitudes for students
      completing required rotations (OR = 1.6, 95% CI 1.2 to 2.2, p = 0.002) and for
      students completing rotations before or in proximity to when they chose careers
      (OR = 1.7, 95% CI 1.1 to 2.4, p = 0.01). Ninety percent of the 543 students who
      had ambulatory rotations were satisfied with the experience. Thirty-eight percent
      of the highly satisfied students chose internal medicine careers, compared with
      21% of the students who had low or moderate satisfaction (p = 0.0001).
      CONCLUSIONS: An ambulatory rotation is strongly associated with positive
      perceptions of, attraction to, and choice of a career in internal medicine.
      Research is needed to determine specific components of an effective rotation.
      Further development of ambulatory rotations could help attract more students to
      internal medicine.

PMID- 8576771
TI  - Physician malpractice: does the past predict the future?
AB  - OBJECTIVE: To assess whether there is a population of physicians who have
      consistently poor malpractice claims experiences over time. DESIGN: Retrospective
      cohort study. POPULATION: 12,730 physicians insured in New Jersey from 1977 to
      1991. MAIN OUTCOME MEASURES: After adjusting for specialty, the physicians were
      grouped according to who had the highest, very high, and high rates of
      malpractice claims, approximating 1%, 5%, and 10% respectively, of the insured
      population. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were
      calculated comparing the physicians in these high-risk categories with the other
      physicians. RESULTS: Of the 55 physicians who had the highest malpractice claims
      rates during the first four years, two (3.6%) were in the highest group during
      the subsequent three years (OR 2.8; 95% CI 0.7 to 10.8), five (9.1%) were in the
      very high group (OR 2.0; 95% CI 0.7 to 5.3), and 11 (20%) were in the high group
      (OR 2.3; 95% CI 1.1 to 4.6). Of the 260 physicians in the very high group during
      the first four years, 11 (4.2%) were in the highest group during the subsequent
      three years (OR 3.6; 95% CI 1.8 to 6.4), 26 (10.0%) were in the very high group
      (OR 2.3; 95% CI 1.5 to 3.6), and 46 (17.7%) were in the high group (OR 2.0; 95%
      CI 1.4 to 2.8). Of the 947 physicians in the high group during the first four
      years, 24 (2.5%) were in the highest group during the subsequent three years (OR
      2.3; 95% CI 1.4 to 3.7), 62 (6.6%) were in the very high group (OR 1.5; 95% CI
      1.1 to 1.9), and 118 (12.5%) were in the high group (OR 1.3; 95% CI 1.1 to 1.6).
      Similar results were found when using awards as the outcome. CONCLUSIONS: Most
      physicians who have high malpractice rates during their first four years improve
      over time. Physicians who have high rates of malpractice during one period should
      not be subjected to disciplinary action. However, carefully evaluating physicians
      who consistently have high rates of malpractice during two periods may represent
      an effective strategy for identifying problem physicians.

PMID- 8576772
TI  - Triage decisions for emergency department patients with chest pain: do
      physicians' risk attitudes make the difference?
AB  - OBJECTIVE: To determine whether physicians' risk attitudes correlate with their
      triage decisions for emergency department patients with acute chest pain. DESIGN:
      Cohort. SETTING: The emergency department of a university teaching hospital.
      PATIENTS: Patients presenting to the emergency department with a chief complaint
      of acute chest pain. PHYSICIANS: All physicians who were primarily responsible
      for the emergency department triage of at least one patient with acute chest pain
      from July 1990 to July 1991. METHODS: The physicians' risk attitudes were
      assessed by two methods: 1) a new, six-question risk-taking scale adapted from
      the Jackson Personality Index (JPI), and 2) the Stress from Uncertainty Scale
      (SUS). RESULTS: The physicians who had high risk-taking scores ("risk seekers")
      admitted only 31% of the patients they evaluated, compared with admission rates
      of 44% for the medium scores and 53% for the physicians who had low risk-taking
      scores ("risk avoiders"), p < 0.001. After adjustment for clinical factors, the
      patients triaged by the risk-seeking physicians had half the odds of admission
      [odds ratio (OR) 0.51, 95% confidence interval (95% CI) 0.27 to 0.97], and the
      patients triaged by the risk-avoiding physicians had nearly twice the odds of
      admission (OR 1.83, 95% CI 1.10 to 3.03) of the patients triaged by the medium
      risk scoring physicians. The SUS did not correlate significantly with admission
      rates. Of the 92 patients released home by the risk-seeking physicians, 91 (99%)
      were known to be alive four to six weeks afterwards and one was lost to follow
      up; among the 66 patients released by the risk-avoiding physicians, 64 (97%) were
      known to be alive at four to six weeks, one was lost to follow-up, and one died
      of ischemic heart disease during a subsequent hospitalization (p = NS).
      CONCLUSIONS: The physicians' risk attitudes as measured by a brief risk-taking
      scale correlated significantly with their rates of admission for emergency
      department patients with acute chest pain. These data do not suggest that the
      risk-seeking physicians achieved lower admission rates by releasing more patients
      who needed to be in the hospital, but an adequate evaluation of the
      appropriateness of triage decisions of risk-seeking and risk-avoiding physicians
      will require further study.

PMID- 8576773
TI  - Discrimination and abuse experienced by general internists in Canada.
AB  - OBJECTIVE: To identify the frequency of psychological and emotional abuse, gender
      discrimination, verbal sexual harassment, physical sexual harassment, physical
      assault, and homophobia experienced by general internists. DESIGN: Cross
      sectional survey. SETTING: Canadian general internal medicine practices. RESULTS:
      The overall response rate was 70.6% (984/1,393); the 501 respondents who
      classified themselves as general internists were studied. Three-fourths of the
      internists experienced psychological and emotional abuse at the hands of
      patients, and 38% of the women and 26% of the men experienced physical assault by
      patients. The majority of the female internists experienced gender discrimination
      by patients (67%) and by physician peers (56%). Forty-five percent of the women
      experienced verbal sexual harassment by patients, and 22% experienced physical
      sexual harassment by patients. The male internists experienced verbal sexual
      harassment from nurses slightly more often than the female internists did (19% vs
      13%, p > 0.05). Verbal sexual harassment by male colleagues was reported by 35%
      of the female internists, and physical sexual harassment was reported by 11%.
      Approximately 40% of general internists reported homophobic remarks by both
      health care team members and patients. CONCLUSIONS: Abuse, discrimination, and
      homophobia are prevalent in the internal medicine workplace. A direct,
      progressive, multidisciplinary approach is necessary to label and address these
      problems.

PMID- 8576774
TI  - Suicidal ideation among urban medical outpatients.
AB  - The prevalence of current suicidal ideation among urban primary care outpatients
      was assessed, and suicidal and non-suicidal patients were compared with regard to
      their demographic characteristics and their attitudes toward mental health
      screening. Twenty (3.3%) patients reported having thoughts of killing themselves.
      The patients who had suicidal ideation were significantly younger and more
      frequently divorced. Almost all (97.6%) of the patients indicated that their
      physicians should inquire about emotional health issues at some time, and the
      suicidal patients were nonsignificantly more likely to recommend inquiry about
      psychiatric symptoms at every visit (55.0% vs 37.0%, p < 0.11). Only half of the
      suicidal patients reported lifetime histories of mental health treatment. The
      majority (70.2%) of the patients believed that it would be easy to discuss mental
      health problems with their medical physicians. Among the patients who had
      previously received psychiatric treatment, the suicidal patients were nearly
      three times more likely to anticipate that it would be difficult or very
      difficult to talk to their physicians about psychiatric problems. In contrast,
      among the patients who had no history of mental health treatment, there was no
      association between suicidal ideation and anticipated discomfort in talking with
      their physicians about emotional health.

PMID- 8576776
TI  - When the patient abuses the physician.

PMID- 8576775
TI  - The influence of social class on health status: American and British research on
      health inequalities.
AB  - PURPOSE: To summarize recent and past American and British studies on the
      relationship of social class and health status. DATA SOURCES: A systematic review
      of the pertinent British and American literature, including references identified
      from bibliographies of books and recent articles. STUDY SELECTION: Published
      English-language studies that report original or summary data describing
      socioeconomic status and mortality/morbidity are emphasized. DATA SYNTHESIS:
      Social class, whether measured by occupation, income, or education, has a marked
      effect on mortality and morbidity. Use of British and American standardized
      mortality ratios (SMRs) shows that the gap between the advantaged upper
      socioeconomic classes and the disadvantaged lower classes has become wider from
      1930 to 1980. Explanations for this inequality in health status by socioeconomic
      status point to four factors: artefact, social selection, culture/behavior, and
      material/structural conditions. A synthesis of existing literature suggests that
      material deprivation and social deprivation are the most important factors
      contributing to this association, although data from longitudinal studies
      implicate social hierarchy. CONCLUSION: The reviewed studies point to growing
      inequalities in health status between those of lower and those of higher
      socioeconomic status. Clinicians and teachers in internal medicine should
      incorporate this knowledge in assessing patients and adopt a perspective that
      takes account of socioeconomic factors in diagnostic and management decisions.

PMID- 8576777
TI  - Changing approaches to cardiovascular care. Proceedings of the 3rd International
      Mediterranean Symposium on Hypertension. Cannes, France, 24-25 February 1995.

PMID- 8576778
TI  - Multiple risk factors for coronary heart disease in patients with hypertension.
AB  - AIM: Multiple risk factors for coronary heart disease must be considered in order
      to establish both the overall risk status of each hypertensive patient and the
      most appropriate therapeutic approach. CORONARY HEART DISEASE AND HYPERTENSION:
      Particular attention is required for those risk factors that are more prevalent
      in hypertensive patients. Guidelines for their recognition have been provided.

PMID- 8576779
TI  - Managing the elderly hypertensive patient beyond blood pressure reduction.
AB  - ANTIHYPERTENSIVE TREATMENT OF THE ELDERLY: Several prospective, randomized, long
      term trials on antihypertensive drug treatment have shown that elderly patients
      with systolic and diastolic or isolated systolic hypertension benefit from a
      reduction in blood pressure. Antihypertensive treatment reduces the overall
      mortality by 20%, cardiovascular mortality by 33%, the incidence of fatal and non
      fatal cerebrovascular events by 40% and the complications of coronary heart
      disease by 15%. In addition, elderly patients have a high risk of overt or latent
      and asymptomatic cardiovascular diseases. For this reason, not only
      antihypertensive treatment, but also risk factor modification (such as
      cholesterol reduction therapy) is, in absolute terms, more beneficial in elderly
      patients than in middle-aged patients, particularly in patients with concomitant
      cardiovascular diseases and other risk factors. QUALITY OF LIFE: Although the
      randomized trials have focused on mortality and morbidity as main endpoints, it
      is questionable whether longevity is a worthwhile social objective in itself.
      Quality of life is an important aspect of antihypertensive treatment, since
      hypertension is generally symptomless while drug therapy may have adverse effects
      on the quality of life. The frequency of adverse effects is similar in both
      middle-aged and elderly hypertensive patients, with about 2% of patients per year
      in both age groups withdrawing from randomized treatment due to objectively
      assessed adverse effects. The rate of subjectively assessed adverse effects
      during treatment is also similar in younger and elderly patients. In general,
      clinical studies have suggested that a blood pressure reduction does not
      influence the well-being of elderly patients, whether measured in physical,
      emotional or social terms. Both calcium antagonists and diuretics have shown an
      age-dependent effect in comparative trials, with a higher blood pressure
      reduction in elderly than in younger patients. CONCLUSION: Antihypertensive
      therapy in elderly hypertensives adds longevity and need not compromise quality
      of life. Although the reduction and normalization of blood pressure is the
      primary goal, the increased availability of antihypertensive preparations and
      drugs for treating concomitant diseases and risk factors allows the physician to
      tailor treatment of the elderly to the needs of the individual patient.

PMID- 8576780
TI  - Practical relevance of the 24-hour trough: peak ratio of antihypertensive drugs.
AB  - INTRODUCTION OF THE TROUGH:PEAK RATIO: The mean antihypertensive effect of a
      drug, measured just before the next dose in a multiple-dose regimen, is generally
      used as a criterion for approval by regulatory agencies. However, for many short
      acting drugs very high doses may be required to maintain some antihypertensive
      activity at the end of the dosing interval. This may lead to an excessive
      reduction in blood pressure at the time of peak drug effect. In order to avoid
      unnecessarily large doses, regulatory agencies have introduced a new standard,
      the trough:peak ratio, which may be 50-60% but should should ideally be higher.
      BENEFITS OF HIGH TROUGH:PEAK RATIO: A high trough:peak ratio indicates a long
      duration of action. This may provide a better risk:benefit ratio compared to
      shorter acting antihypertensive agents by giving optimal therapeutic coverage for
      24 h or even longer. Greater benefit may be gained from better control of
      overnight blood pressure, especially in the early morning hours when both a steep
      rise in blood pressure and a higher rate of cardiovascular events have been
      observed. Large swings in blood pressure may occur when the peak is too high in
      relation to the trough, increasing blood pressure variability, which may in turn
      increase target organ damage. A high trough:peak ratio may protect the patient
      against drug-induced blood pressure fluctuations. It may also produce fewer
      adverse effects as the blood pressure may fall further and the onset of action
      may be more gradual. This, together with an effective single daily dose, may
      increase patient compliance. Furthermore, an antihypertensive effect that lasts
      more than 24 h protects the patient against a rapid loss of blood pressure
      control when a dose is omitted or delayed. TROUGH:PEAK RATIO OF AVAILABLE
      ANTIHYPERTENSIVE DRUGS: We performed a literature survey to evaluate the
      practical relevance of the trough:peak ratio and to determine how it might help
      in the choice of antihypertensive agents. The results suggested that not all
      single daily doses of angiotensin converting enzyme inhibitors or calcium
      antagonists had a trough:peak ratio of > 50%. We conclude that specially
      designed, prospective clinical trials should be conducted to address this issue.

PMID- 8576781
TI  - Guidelines for the treatment of hypertension: an American view. Fifth Joint
      National Committee.
AB  - REPORT OF FIFTH JOINT NATIONAL COMMITTEE: The 1993 report of the Fifth Joint
      National Committee presents the position of most United States hypertension
      experts. CRITICISMS: Sharp criticisms have been voiced on two of the major points
      of the fifth report of the Joint National Committee, the threshold for therapy
      and the choice of initial therapy. In addition, there is continued uncertainty
      about the appropriate goal for therapy.

PMID- 8576782
TI  - Guidelines for the management of hypertension: the World Health
      Organization/International Society of Hypertension view. World Health
      Organization. International Society of Hypertension.
AB  - ORGANIZATIONS PRODUCING GUIDELINES: Guidelines or recommendations for the
      management of hypertension have periodically been produced by various
      organizations or specialized scientific societies, in particular the United
      States Joint National Committee on the Detection, Evaluation and Treatment of
      High Blood Pressure and the World Health Organization/International Society of
      Hypertension Guidelines Sub-Committee. SIMILARITIES, DIFFERENCES AND EVALUATION
      OF GUIDELINES: There are many similarities between the different guidelines and
      any dissimilarities are mainly related to the choice of first-line drugs for
      treatment and the goal of treatment. In formulating guidelines it is important to
      avoid placing rigid constraints on practising doctors' decisions while helping
      them to exert the most careful and informed judgement in individual cases.

PMID- 8576783
TI  - Main objectives and new aspects of combination treatment of hypertension.
AB  - AIM: To review the various pharmacological approaches currently proposed for the
      treatment of hypertension. RESULTS: With the evolution of pharmacological
      treatment of hypertension, various classes of agent (diuretics, beta-blockers,
      angiotensin converting enzyme inhibitors, calcium antagonists and alpha 1
      blockers) have become available for the initiation of antihypertensive therapy.
      As monotherapy, each type of agent will normalize blood pressure in about half of
      all hypertensive patients. Replacing one drug with another that acts through a
      different mechanism improves the probability of controlling blood pressure.
      Another way to increase the number of responders is to increase the dose;
      however, this often results in more side effects. A preferable way of improving
      efficacy is to combine low doses of drugs that have different impacts on the
      cardiovascular system, thus opposing the compensatory responses that tend to
      limit the blood pressure drop. CONCLUSION: Low-dose drug combinations are
      generally well tolerated and the treatment of hypertension can be simplified by
      using fixed-dose combinations. These combinations have the potential to become a
      valuable alternative in the initiation of antihypertensive therapy.

PMID- 8576784
TI  - The pharmacological basis for the combination of calcium channel antagonists and
      angiotensin converting enzyme inhibitors in the treatment of hypertension.
AB  - IMPROVING THE TREATMENT OF HYPERTENSION: The results of basic and clinical
      research in hypertension over the last 30 years have shown that this disease
      cannot be treated merely by inducing vasodilation and a fall in blood pressure.
      The development of high blood pressure is associated with changes in carbohydrate
      and lipid metabolism and with the development of organ damage, mainly of the
      heart and kidneys. It is now clear that different elements of blood pressure
      control mechanisms can lead to hypertension, emphasizing the need to select the
      appropriate type of hypertensive drug in treating different patients. COMBINATION
      OF CALCIUM CHANNEL ANTAGONISTS AND ANGIOTENSIN CONVERTING ENZYME (ACE)
      INHIBITORS: Calcium channel antagonists and ACE inhibitors have synergistic
      effects on sodium and fluid balance and on the renin-angiotensin-aldosterone
      system. Thus a combination of these two antihypertensive drug classes is likely
      to be beneficial in certain subgroups of patients with hypertension. Large
      clinical trials are needed to determine whether this is indeed the case.

PMID- 8576785
TI  - The heart and vascular changes in hypertension.
AB  - AIM: To review present knowledge on the causes of cardiovascular changes in
      hypertension and on the effects of antihypertensive treatment. BACKGROUND: The
      clinical manifestations of hypertensive heart disease have changed considerably
      in recent decades, from predominantly cardiac failure to predominantly left
      ventricular hypertrophy, which is an independent risk factor for all
      cardiovascular events. This change parallels the recent development of ultrasonic
      devices which make it possible to investigate the vessels as well as the heart.
      These devices have shown that there are different types of cardiac remodeling,
      which are associated with different hemodynamic profiles. TREATMENT OF
      CARDIOVASCULAR REMODELING: Recent studies have shown that antihypertensive
      treatment, both pharmacological and non-pharmacological, can significantly reduce
      left ventricular hypertrophy in hypertensive patients without jeopardizing the
      hemodynamic balance. However, hypertensive vessel disease has been less
      extensively investigated, with many studies concentrating on the carotid
      arteries. There appears to be a correlation between cardiac and carotid artery
      changes but so far there is no information on the effects of the antihypertensive
      treatment on the carotid alterations.

PMID- 8576786
TI  - Large artery function and alterations in hypertension.
AB  - HYPERTENSION AND ARTERIAL HEMODYNAMICS: One of the characteristics of
      hypertension is an impairment in arterial hemodynamics. Any definition of
      hypertension has to take account of oscillatory fluctuations during the cardiac
      cycle, that is, fluctuations in systolic and diastolic blood pressure around mean
      arterial pressure. These fluctuations are determined by ventricular ejection,
      arterial distensibility and the timing of arterial wave reflections. EFFECTS OF
      AGING ON LARGE ARTERIES: Larger arteries stiffen progressively with age, due to
      medial and intimal thickening. This alteration can be described as a decrease in
      arterial distensibility (Di = delta D/delta P x D, where D is the diameter of the
      artery and P is the blood pressure). The most obvious consequence of arterial
      stiffening is an increase in the amplitude of pulse pressure, caused by an
      increase in systolic pressure and a decrease in diastolic pressure. Two
      mechanisms underlie this increase in pulse pressure: a higher incident pressure
      wave generated by the left ventricle into a stiffened aorta and an increase in
      the velocity of the pressure wave traveling forward and back in the arterial
      tree. In young subjects, the reflected wave causes an increase in the early
      diastolic wave, but in older people the reflected wave is summed with a late
      systolic wave, causing a dramatic increase in central systolic pressure. These
      phenomena affect left ventricular function adversely, increasing myocardial
      oxygen consumption and tending to decrease coronary blood flow. Furthermore, the
      increased systolic blood pressure induces left ventricular hypertrophy. EFFECTS
      OF ANTIHYPERTENSIVE DRUGS: Although all classes of antihypertensive drugs can
      reduce blood pressure, only some can decrease arterial distensibility.
      Angiotensin converting enzyme inhibitors and calcium antagonists have been shown
      to decrease the stiffness of conduit arteries and dilate peripheral arteries.
      This may account for the superiority of these drugs in regressing left
      ventricular hypertrophy.

PMID- 8576787
TI  - Endothelium-derived vasoactive factors in hypertension: nitric oxide and
      endothelin.
AB  - ENDOTHELIUM-DERIVED NITRIC OXIDE: The endothelium is a source of vasoactive
      factors among which the most relevant are nitric oxide and endothelin. Nitric
      oxide is synthesized from L-arginine by a family of nitric oxide synthases and is
      a widespread biological mediator. It is implicated in many physiological and
      pathophysiological processes, including a variety of cardiovascular diseases like
      hypertension. NITRIC OXIDE AND HYPERTENSION: The release of nitric oxide seems to
      be modulated by changes in blood pressure. However, the role of nitric oxide in
      hypertension is still controversial and seems to vary depending on the stage of
      the disease and the model studied. In spontaneous hypertension, the production of
      nitric oxide is increased but inefficacious, probably because of increased
      inactivation or scavenging. In the heart the production of nitric oxide seems to
      be increased, probably as a compensatory mechanism against hypertension. In salt
      induced hypertension, nitric oxide production may be impaired. In human
      hypertension, pharmacological experiments reveal an impaired nitric oxide dilator
      mechanism. In pulmonary hypertension, the use of nitric oxide gas inhalation has
      been proposed as a future therapy for this condition. ENDOTHELIN: Endothelin-1 is
      a potent vasoconstrictor peptide produced and released from endothelial cells. In
      isolated blood vessels, endothelin causes profound contraction. The hemodynamic
      effects of endothelin can be explained by the activation of two endothelin
      receptors, ETA and ETB. The relationship between endothelin and hypertension is
      not clear. Although plasma endothelin levels are normal in most patients with
      essential hypertension, the hypertensive blood vessel wall may contract more
      profoundly in response to the peptide; hence, endothelin antagonists may have
      antihypertensive effects in patients with hypertension.

PMID- 8576788
TI  - Hypertension and coronary artery disease: cause and effect.
AB  - NATURE OF RELATIONSHIP BETWEEN HYPERTENSION AND CORONARY ARTERY DISEASE:
      Epidemiological data indicate a strong and consistent link between hypertension
      and coronary artery disease. This does not mean that hypertension is the cause of
      coronary artery disease. Less than a quarter of the risk of developing coronary
      artery disease can be attributed to raised blood pressure. Furthermore, in
      individuals, hypertension is only weakly predictive and hence blood pressure
      cannot be relied upon to identify those with a particularly high risk. EFFECT OF
      A REDUCTION IN BLOOD PRESSURE ON CORONARY ARTERY DISEASE: The results of outcome
      trials, largely in men with mild to moderate uncomplicated hypertension,
      demonstrate that a modest short-term reduction in blood pressure confers a
      reduction in coronary artery disease events of about 16%, against the expectation
      from observational studies of about 22.5%. Explanations for the apparent
      shortfall include the putative theory that metabolic effects of the drugs used in
      the trials (mainly thiazides and beta-blockers) offset the beneficial effect of
      the blood pressure reduction. However, from consideration of epidemiological
      findings, it is clear that a large proportion (over 75%) of events in
      hypertensive patients is unlikely to be preventable by managing the elevated
      blood pressure alone. TREATMENT CONSIDERATIONS: Since arterial pressure interacts
      in a more than additive manner with coincident coronary risk factors, treatment
      should be initiated on the basis of overall risk and directed by predictors of
      myocardial infarction. In addition to a sustained level of blood pressure, these
      predictors include established coronary artery disease, older age and cigarette
      smoking. BEYOND BLOOD PRESSURE REDUCTION: Whether metabolically neutral
      antihypertensive drugs can reduce the shortfall between expected and observed
      benefit remains uncertain. However, some newer agents (angiotensin converting
      enzyme inhibitors and calcium antagonists) appear to have an effect on vascular
      structure and function that is independent of blood pressure reduction. If these
      advantages are confirmed in clinical trials, these drugs offer the prospect of a
      much greater impact on coronary artery disease than currently obtained.

PMID- 8576789
TI  - Update on the use of angiotensin converting enzyme inhibitors and calcium
      antagonists in postinfarction patients.
AB  - AIM: To review the results of recent studies on the use of angiotensin converting
      enzyme (ACE) inhibitors and calcium antagonists in patients after an acute
      myocardial infarction. METHOD: Literature review. CONCLUSIONS: ACE inhibition
      reduces mortality and morbidity and improves quality of life in a cost-effective
      way, demonstrating increased benefits with increasing risks. Calcium antagonism
      with verapamil and possibly diltiazem reduces mortality and morbidity, except in
      patients with congestive heart failure without signs of reversible myocardial
      ischaemia. Nifedipine may have negative effects. The efficacy of the second
      generation dihydropyridines remains to be demonstrated.

PMID- 8576790
TI  - Insulin resistance and hyperinsulinemia in hypertension.
AB  - GENETIC PREDISPOSITION: Insulin resistance and reactive hyperinsulinemia occur
      not only with obesity, impaired glucose tolerance or non-insulin-dependent (type
      2) diabetes mellitus, but also in many non-obese, non-diabetic patients with
      essential hypertension and their currently normotensive, lean, young offspring,
      as well as in some other conditions known to promote hypertension. Insulin
      resistance impairs glucose tolerance, while insulin resistance and/or
      hyperinsulinemia promote dyslipidemia, body fat deposition and probably
      atherogenesis. Therefore, the common coexistence of a genetic predisposition for
      hypertension with insulin resistance helps to explain the frequent, although
      temporally often dissociated, occurrence of hypertension together with
      dyslipidemia, obesity and type 2 diabetes in a given patient. INSULIN RESISTANCE
      AND HYPERINSULINEMIA AS SLOW PRESSOR MECHANISMS: In the pathogenesis of
      hypertension, inappropriate vasoconstriction (due to an imbalance of vasoactive
      substances and/or raised cytosolic calcium) and/or structural vasculopathy is
      particularly important. Among the mosaic of assumed pressor mechanisms, distinct
      Na+ retention is almost invariably involved in diabetes mellitus, while
      sympathetic activation tends to occur in essential hypertension, particularly in
      association with obesity. Insulin resistance may develop as a consequence of an
      intracellular excess of Ca2+ or a decrease in Mg2+, an impaired insulin-mediated
      rise in skeletal muscle blood flow, increased sympathetic activity or excess body
      weight. Acute hyperinsulinemia causes arterial vasodilation on one hand and
      increases sympathetic activity and renal Na+ reabsorption on the other.
      Chronically, hyperinsulinemia may promote cardiovascular muscle cell
      proliferation and atherogenesis, while insulin resistance may be associated with
      certain transmembraneous cation transporters, leading to an increase in cytosolic
      Ca2+. Hyperinsulinemia and/or insulin resistance may also be associated with an
      increased blood pressure sensitivity to high salt intake. In the mosaic of many
      different blood pressure-raising mechanisms, insulin resistance and/or
      hyperinsulinemia is likely to represent an amplifying slow or very slow pressor
      factor.

PMID- 8576792
TI  - Risk factors for non-insulin-dependent diabetes mellitus.
AB  - RISK FACTORS AND PREDICTORS: The risk factors for non-insulin-dependent diabetes
      mellitus (NIDDM) include age, overall adiposity, an adverse body fat
      distribution, adverse glucose and insulin concentrations, insulin resistance and
      lack of physical exercise. The strongest predictors of NIDDM appear to be
      metabolic factors, including impaired glucose tolerance and insulin resistance.
      TREATMENT: Pharmacological agents that improve insulin sensitivity are being
      tested in multicenter clinical trials. In patients with a high risk of NIDDM, it
      seems prudent to avoid the use of pharmacologic agents that increase insulin
      resistance.

PMID- 8576791
TI  - Structural cardiovascular alterations and blood pressure variability in human
      hypertension.
AB  - AIM: To evaluate the cardiovascular risk of hypertensive patients in relation to
      left ventricular hypertrophy, arteriolar hypertrophy and blood pressure
      variability, and the effects of antihypertensive treatment. LEFT VENTRICULAR
      HYPERTROPHY: In hypertensive subjects with marked left ventricular hypertrophy,
      cardiovascular problems are about three times more frequent than in hypertensives
      who do not have left ventricular hypertrophy. The evidence suggests, however,
      that a moderate degree of left ventricular hypertrophy may be compensatory and
      that regression of mild hypertrophy should not necessarily be pursued. ARTERIOLAR
      HYPERTROPHY: An increased wall to lumen ratio leads to an increase in vascular
      resistance and thus promotes hypertension. Regression of this alteration with
      antihypertensive treatment appears to be both beneficial and achievable, although
      it is not clear whether all antihypertensive agents have the same effect.
      Moreover, there are methodological problems in determining whether a regression
      has actually been achieved. BLOOD PRESSURE VARIABILITY: There is evidence to
      suggest that end-organ damage is more frequent and more marked in hypertensives
      with greater 24 h blood pressure variability. It appears that antihypertensive
      treatment does not easily reduce this variability, although the intermittent
      measurements taken by automatic monitoring devices do not fully reflect patterns
      of blood pressure variation. It may be that hypertensives with a greater degree
      of blood pressure variability can obtain a reduction in the magnitude of this
      variability with antihypertensive treatment.

PMID- 8576793
TI  - Metabolic aspects of the treatment of hypertension.
AB  - INSULIN RESISTANCE AND HYPERTENSION: Hypertension is often associated with
      insulin resistance, which may be the underlying cause of hypertension in many
      cases. The whole complex of insulin resistance and its related factors appears to
      be based on a reduction in nutritional blood flow to large muscle groups. EFFECT
      OF TREATMENT: Blood flow is further reduced during beta-blockade but improves
      during alpha 1-blockade, which may explain the contrasting effects of these
      treatments on insulin resistance and triglyceride metabolism.

PMID- 8576794
TI  - Hypertension in the non-insulin-dependent diabetes mellitus syndrome: a critical
      review of therapeutic intervention.
AB  - BACKGROUND: Since it is not yet clear whether and to what degree treatment of
      mild hypertension will decrease cardiovascular morbidity and mortality in non
      insulin-dependent diabetes (NIDDM), decisions concerning the treatment of
      hypertension diabetics are at present based on data from the non-diabetic
      population. RECENT RESEARCH ON CAUSES OF DIABETES: A large body of recent work on
      the sequence of events leading from the prediabetic to the hyperglycemic stages
      of the NIDDM syndrome has suggested that elevated blood pressure and other
      cardiovascular risk factors may precede NIDDM by many years and that after the
      onset of NIDDM intervention might be too late to be beneficial. PROSPECTIVE
      INTERVENTION STUDY IN PROGRESS: It is not possible to draw firm conclusions that
      can be applied to the treatment of hypertensive diabetics before the results of
      the United Kingdom Prospective Diabetes Study/Hypertension in Diabetes Study are
      published later this decade. Unfortunately, this study does not consider
      different stages within the NIDDM syndrome. Moreover, World Health Organization
      criteria are not used for the diagnosis of either NIDDM or hypertension, so that
      the study subjects are insufficiently characterized. Finally, confounding
      variables such as racial, ethnic and sex differences and the individual stage of
      the NIDDM syndrome (and consequent variation in antidiabetic treatment) have been
      either not considered or not completely ruled out. These shortcomings seriously
      threaten the significance of this otherwise important study. CONCLUSIONS: As long
      as there are no diabetes-specific data from adequately sized intervention
      studies, recommendations for antihypertensive treatment in NIDDM will be based on
      strategies accepted for the non-diabetic population. These recommendations
      involve symptom-based diagnostic and therapeutic concepts of both NIDDM and
      hypertension and ignore recent pathogenetic concepts which could lead to an
      interdisciplinary and integrated approach to cardiovascular risk management, and
      possibly to the prevention of end-stage NIDDM syndrome with its advanced
      macrovascular complications.

PMID- 8576795
TI  - Prognostic significance of albuminuria for the development of nephropathy.
AB  - FACTORS IN RENAL DISEASE: The factors that affect the development of renal
      disease are the same as those that influence its progression, that is, glycaemic
      control, blood pressure and albumin excretion rate. EFFECTS OF TREATMENT: Many of
      these factors are modifiable by treatment and their modification appears to delay
      the evolution of diabetic nephropathy. Of primary importance is the treatment and
      reduction of albuminuria, microalbuminuria in particular.

PMID- 8576796
TI  - Effects of angiotensin converting enzyme inhibitors on the progression of
      diabetic nephropathy.
AB  - AIM: To review recent studies on the effect of angiotensin converting enzyme
      (ACE) inhibitors on diabetic nephropathy. METHOD: Literature review. RESULTS:
      Strict glucose control, a low protein intake and aggressive blood pressure
      control are the main requirements for the preservation of renal function in
      patients with diabetes mellitus. Recent work has shown that ACE inhibitors have
      renoprotective actions in diabetes that go beyond their capacity to lower blood
      pressure. Through these actions they slow the progression of renal failure and
      prevent the development of macroalbuminuria that characterizes the onset of
      diabetic nephropathy. CONCLUSIONS: ACE inhibitors may be considered the drugs of
      choice in diabetic patients with either hypertension or some degree of renal
      dysfunction.

PMID- 8576797
TI  - Angiotensin converting enzyme inhibitors and calcium antagonists alone or
      combined: does the progression of diabetic renal disease differ?
AB  - BACKGROUND: Over the past two decades numerous studies have evaluated the effects
      of angiotensin converting enzyme (ACE) inhibitors and calcium antagonists on
      proteinuria and the progression of diabetic renal disease. Taken together, these
      studies suggest that certain types of calcium antagonists and ACE inhibitors have
      distinctive advantages over conventional antihypertensive agents with regard to
      improving overall and renal survival. Among the unique actions of these two
      classes of drugs are their effects on matrix proteins apart from their effects in
      reducing arterial pressure. CONCLUSIONS FROM LITERATURE SURVEY: There is no
      definitive answer to the question of whether the effects of ACE inhibitors and
      calcium antagonists are additive when the drugs are used together. However,
      preliminary data from both animal and clinical studies suggest that combinations
      of non-dihydropyridine calcium antagonists and ACE inhibitors produce an
      additional fall in proteinuria and have more favorable side effect profiles than
      results observed with either drug alone. Therefore, combination therapy with
      these agents may be valuable, especially in diabetic patients with renal
      insufficiency in whom arterial pressure is difficult to control.

PMID- 8576798
TI  - Congenital sucrase-isomaltase deficiency.

PMID- 8576799
TI  - Radiolucent pancreatic lithiasis.

PMID- 8576800
TI  - Extensive esophageal candidiasis in the absence of oral lesions in pediatric
      AIDS.

PMID- 8576801
TI  - Infantile Helicobacter pylori associated with thickened gastric folds.

PMID- 8576802
TI  - Intravenous ribavirin therapy for adenovirus gastroenteritis after bone marrow
      transplantation.

PMID- 8576803
TI  - Fungemia with Saccharomyces boulardii in a 1-year-old girl with protracted
      diarrhea.

PMID- 8576804
TI  - The interplay between enteric pathogens and gastrointestinal mucins.

PMID- 8576805
TI  - A selective advantage for cystic fibrosis carriers.

PMID- 8576806
TI  - Dissolution of a barium impaction ileus in a child using the PIEE procedure.

PMID- 8576807
TI  - Ulcerative colitis in children 10 years old and younger: comparison with Crohn's
      disease.

PMID- 8576808
TI  - Childhood intussusception: management perspectives in 1995.

PMID- 8576809
TI  - Cysteine supplementation and reduction of total parenteral nutrition-induced
      hepatic lipid accumulation in the weanling rat.
AB  - Total parenteral nutrition (TPN)-induced hepatic steatosis is the most common
      complication of TPN administration to humans. The mechanism of TPN-induced
      hepatic steatosis has not been studied in young mammals. The goal of this study
      was to determine the mechanism of TPN-induced hepatic steatosis in the weanling
      rat and the effect of supplementation of TPN with choline and/or cysteine on TPN
      induced hepatic steatosis. In the weanling rat, we investigated the effect of TPN
      administration on histologic hepatic steatosis, total hepatic lipid, hepatic
      acetyl-CoA-carboxylase (ACC--the rate limiting enzyme in fatty acid synthesis)
      specific activity, and total plasma lipids. TPN administration resulted in a
      threefold increase in hepatic lipid as compared with control and sham animals
      (TPN 138 +/- 12 mg/g liver versus control 57 +/- 1), an increase in histologic
      steatosis (TPN 3.7 versus control 1.3), and a decline in total plasma lipid (TPN
      2.1 +/- 0.3 g/L versus control 4.1 +/- 0.3). TPN-induced hepatic steatosis in the
      weanling rat was not associated with an increase in ACC specific activity (TPN
      2.10 +/- 0.33 nmol/min/mg protein versus control 2.85 +/- 0.23). Supplementation
      of the TPN with choline (15 mg/day) did not significantly lessen hepatic
      steatosis; however, supplementation of TPN with cysteine (2.5 mg/day) or with
      cysteine and choline did result in a significant lessening of hepatic lipid
      content and of histologic steatosis and a normalization of total plasma
      lipid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8576810
TI  - Are bilirubin and plasma lipid profiles of premature infants dependent on the
      lipid emulsion infused?
AB  - The effect of a lipid emulsion containing long-chain triglycerides (LCT) and
      supplemented with L-carnitine on plasma lipids and bilirubin in premature
      neonates on total parenteral nutrition was compared to that of lipid emulsions
      containing either LCT or a mixture of LCT and medium-chain triglycerides (MCT).
      In a double-blind randomized study 49 premature neonates received one of the
      three fat emulsions, given intravenously, over 16-20 h daily for 6 days. Plasma
      carnitine levels increased significantly in the supplemented group only; the
      addition of carnitine did not seem to affect any of the parameters studied. Mean
      plasma triglycerides rose by 193 and 199% in the carnitine-supplemented and the
      LCT groups, respectively, and by 314% in the MCT/LCT group. On the sixth day of
      the study free fatty acids were significantly higher in the MCT/LCT group than in
      the other two groups. Plasma phospholipids and free cholesterol increased (p <
      0.05) progressively in all groups and were correlated (r = 0.74, p < 0.001). At
      the end of the 6-day study all groups showed a similar decline in free and total
      bilirubin levels despite the significant increase in plasma lipids and free fatty
      acids resulting from the stepwise increase in lipid load. No correlation was
      found between free fatty acids and free bilirubin. Since hyperbilirubinemia and
      hypertriglyceridemia appear to be clinically independent factors, the infusion of
      lipids should not be withheld from jaundiced infants on total parenteral
      nutrition.

PMID- 8576811
TI  - Estimation of arachidonic acid synthesis in full term neonates using natural
      variation of 13C content.
AB  - Neonates need arachidonic acid (AA) for their growing tissues, but it is unknown
      to what extent they can synthesize AA from dietary linoleic acid (LA). We studied
      infantile AA synthesis by using different natural 13C amounts in dietary fats.
      The diets of four infants ages 18 +/- 4 days (mean +/- SD) with newly diagnosed
      phenylketonuria were changed from breast milk or formula to a phenylalanine-free
      diet with corn oil as the only fat source. Compared with most dietary fats in
      Europe derived from C3 plants, corn oil LA has a higher 13C content. We
      determined the 13C content of LA and AA in 0.25-0.5 ml serum before and for 3-4
      days after the diet change with gas chromatography combustion isotope ratio mass
      spectrometry (GC-IRMS). Baseline delta 13C values were -31.5 +/- 1.1% (mean +/-
      SD) for serum LA and -30.1 +/- 1.2% for AA. The corn oil diet induced changes of
      delta 13C values over baseline in LA of 8.9 +/- 1.0 on day 1 and 12.7 +/- 0.7 on
      day 4, respectively. The changes of AA delta 13C values were 0.5 +/- 0.7 and 2.7
      +/- 0.7 on days 1 and 4. We conclude that reproducible detection of differences
      in delta 13C values of fatty acids in small samples of infantile serum, induced
      by dietary variation of natural 13C amounts, is feasible with GC-IRMS. Since the
      corn oil diet did not contain AA, the observed change of AA delta 13C shows
      active endogenous AA synthesis in full-term neonates.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8576812
TI  - Receptor-mediated binding of milk lactoferrin to nursing piglet enterocytes: a
      model for studies on absorption of lactoferrin-bound iron.
AB  - Lactoferrin, an iron-binding glycoprotein that is abundant in milk of some
      species, has been suggested to play a key role in the absorption of iron in human
      infants. This hypothesis is based on the dominant role of lactoferrin as an iron
      binding component in human milk and on the occurrence of lactoferrin receptors in
      brush-border membranes in infants' intestines. The piglet may be a useful model
      to evaluate the biological activity of lactoferrin because we have previously
      found the presence of a lactoferrin receptor in brush-border membranes from
      suckling piglets. In this study, viable enterocytes were isolated from 6- to 20
      day-old suckling piglets. Binding studies were performed at 4 degrees C using
      125I-labeled porcine lactoferrin. Scatchard analysis of equilibrium binding data
      showed an apparent binding constant (Kd) of 2 x 10(-6) M (SD = 0.6 x 10(-6)).
      This affinity is in close agreement with previous results obtained using isolated
      brush-border membrane vesicles. Bovine lactoferrin inhibited the binding of
      porcine lactoferrin. Porcine transferrin, however, did not affect porcine
      lactoferrin binding significantly. Thus, lactoferrin binding is highly specific.
      When enterocytes were incubated with 125I-labeled lactoferrin at 37 degrees C,
      the amount of cell-associated radioactivity exceeded the surface binding capacity
      of the cells by almost fivefold. This finding agrees with the continuous binding
      and subsequent internalization of 125I-labeled lactoferrin. The isolated piglet
      enterocyte seems to provide a useful model for further studies of the mechanism
      of receptor-mediated absorption of lactoferrin.

PMID- 8576813
TI  - Polyamine profiles in human milk, infant artificial formulas, and semi-elemental
      diets.
AB  - Using a sensitive high-performance liquid chromatography method, we quantified
      the concentration of polyamines (putrescine, spermidine, and spermine) in human
      milk as well as in a representative group of commonly used artificial infant
      formulas. Variations in polyamine levels were also analyzed in human milk during
      the immediate postnatal period. During the first week postpartum, putrescine
      levels in human milk remained very low and varied little, while spermidine and
      spermine concentrations rose markedly during the first 3 days, reaching plateau
      levels that were 12 and eight times higher, respectively, than the values
      measured on day 0. The mean total polyamine concentration was 557 +/- 18 nmol/dl
      with the following profile: spermine, 313 +/- 16; spermidine, 220 +/- 20; and
      putrescine, 24 +/- 3.5. In artificial powdered formulas, the polyamine
      concentration was approximately 10 times lower than in human milk, with no
      difference in putrescine and spermine contents between first-age and second-age
      formulas. By contrast, semi-elemental diets prepared by hydrolytic procedures
      using crude extracts of pancreatic enzymes were shown to be major sources of
      polyamines with a profile similar to that of human milk. Compared with first-age
      formulas, mean concentrations in spermine and spermidine were 39 and six times
      higher, respectively, in these semi-elemental diets, whereas putrescine levels
      remained almost equivalent in all types of milk tested. These data indicate that
      human milk and some semi-elemental diets provide substantial amounts of spermine
      and spermidine to neonates and infants that could potentially modulate intestinal
      maturation.

PMID- 8576814
TI  - The trophic action of human growth hormone on human duodenal mucosa cultured in
      vitro.
AB  - The influence of human growth hormone (hGH) on crypt cell proliferation in
      cultured explants of human duodenal mucosa has been studied, using a
      stathmokinetic technique with crypt microdissection. The addition of hGH (0.004
      IU/ml) to paired duodenal explants from eight patients significantly increased
      epithelial crypt cell proliferation (p < 0.001), showing that hGH has a trophic
      action on the human duodenal mucosa in vitro.

PMID- 8576815
TI  - Enhancement of lysozyme trypsin-mediated decay of intestinal bifidobacteria and
      lactobacilli.
AB  - Lysozyme-mediated lysis of Bifidobacteria and Lactobacilli was studied in in
      vitro tests using the agar gel plate and turbidometric Micrococcus luteus
      (lysodeikticus) procedure as a standard. Suspensions of the strains
      Bifidobacterium infantis, B. infantis liberorum, B. breve, B. longum, B. ssp, and
      Lactobacillus acidophilus proved to be resistant to egg white lysozyme and human
      milk lysozyme when incubated at 37 degrees C in concentrations of 5, 50, and 500
      mg lysozyme/L, respectively, through 30 and 60 min. Heat treatment at 100 degrees
      C for 1 h and pretreatment with ether, acetone, ascorbic acid, and hydrogen
      peroxide failed to incline the bacteria to the lytic effects of lysozyme.
      Consecutive incubation of the lysozyme-pretreated bacteria with trypsin resulted
      in a significantly enhanced bacteriolysis in all strains of bacteria, with the
      exception of B. longum. The mode of action of lysozyme and proteolytic enzymes on
      Bifidobacteria and Lactobacilli offers an explanation for the release of
      microbial building blocks and their colonic absorption and retention in the
      breast-fed baby.

PMID- 8576816
TI  - Stated versus actual lipase activity in pancreatic enzyme supplements:
      implications for clinical use.
AB  - We have carried out an independent investigation of the lipase activity of
      several pancreatin preparations, including high-lipase preparations of pancreatin
      that have recently become available. Six preparations from three pharmaceutical
      companies, Cilag, Duphar, and Merck, were analyzed during the recommended shelf
      life of the preparation and included a standard and a high-lipase preparation
      from each manufacturer. All preparations studied showed lipase activity in excess
      of that which was stated on the packets, and in some cases it was more than
      twofold. This has important implications for patients and prescribers since
      changes in apparent enzyme requirements may reflect differences in the potency of
      batches with time. As it is impossible to evaluate capsule requirements with each
      new batch prescribed, the presence or relief of symptoms of malabsorption will
      probably continue to be the way in which most patients monitor their enzyme
      supplementation on a regular basis. We believe that clinicians need to be aware
      of the extent of possible intrinsic variation between individual prescriptions
      before attempting to define possible dose/symptom relationships.

PMID- 8576817
TI  - Striking differences in the incidence of childhood celiac disease between Denmark
      and Sweden: a plausible explanation.
AB  - Among 771 children (381 Swedish and 390 Danish) investigated between 1972 and
      1989 because of suspected celiac disease (CD), 179 proved to have the disease.
      Surprisingly only 24 CD patients were found among the Danish children, compared
      with 155 in the Swedish group, despite the close ethnic, geographical, and
      cultural background of the two populations. The Swedish CD children were
      diagnosed at an earlier age than the Danish children (mean, 1.5 vs. 5.5 years).
      The symptoms of the Swedish patients were dominated by failure to thrive (93 vs.
      71%), whereas a higher proportion of the Danish CD patients suffered from stomach
      pain (21 vs. 5%). Breast-feeding habits were comparable. The estimated content of
      gliadin in the officially recommended diets of the two countries in 1987 differed
      substantially, the Swedish diet containing more than 40 times more gliadin than
      the Danish (4,400 vs. 100 mg) at the age of 8 months, and 4 times more (3,600 vs.
      900 mg) at the age of 12 months. The Danish infant diet differed significantly
      from the Swedish in containing a larger amount of the lower gluten-containing rye
      flour. The earlier introduction of food items with a high gluten content in the
      Swedish compared with the Danish diet seems to be an obvious explanation for the
      great difference in incidence and symptomatology of CD between the two
      populations.

PMID- 8576818
TI  - Endomysial antibodies as unreliable markers for slight dietary transgressions in
      adolescents with celiac disease.
AB  - Adolescents with celiac disease often fail to adhere to a strict gluten-free
      diet. The value of endomysial antibodies in assessing the dietary compliance of
      such adolescents has been assessed in 23 patients divided into four groups
      according to their daily gluten intake. Serum endomysial antibodies were absent
      in all subjects on a gluten-free diet and consistently present in those ingesting
      > 2 g/day of gluten. Only one of six and three of six teenagers with celiac
      disease with an intake of < 0.5 and 0.5-2 g/day, respectively, had endomysial
      antibodies in their serum, despite the presence in three of six and five of six
      of significant changes in the mucosal architecture, as shown by computerized
      morphometry of jejunal biopsies. In conclusion, endomysial antibodies cannot be
      considered a valid marker for slight dietary transgressions.

PMID- 8576819
TI  - Improved energy intakes using amylase-digested weaning foods in Tanzanian
      children with acute diarrhea.
AB  - Amylase from germinating cereal grains enables the preparation of porridge with a
      higher energy density than conventional weaning foods. This food can be combined
      with fermentation, which inhibits pathogen growth. These food technologies are
      inexpensive, can be implemented at the household level, and are therefore
      particularly appropriate for use in developing countries. In a controlled
      clinical trial, 75 children aged 6-25 months admitted to hospital with acute
      diarrhea were rehydrated and then randomly allocated to three corn porridge
      dietary groups: conventional, amylase-digested (AMD), and fermented and amylase
      digested (FAD). The study diets were given ad libitum five times daily, and all
      intakes except breast milk were weighed. Mean daily energy intakes over 4 days in
      the conventional AMD, and FAD groups, respectively, were 32.4 (95% CI 28.7-36.6),
      46.0 (CI 39.6-53.4), and 37.3 (CI 31.8-43.9) kcal/kg/day. The energy intake in
      the AMD group was 42% higher than the conventional group (p = 0.003). There were
      no significant differences between the groups for duration of diarrhea, frequency
      of stooling, or vomiting. Starch digestion using amylase from germination is an
      effective way of improving energy intake in children with acute diarrhea.

PMID- 8576820
TI  - Linear growth after colectomy for ulcerative colitis in childhood.
AB  - Eighteen children and adolescents, of a total of 90 treated in our unit between
      1982 and 1992, underwent colectomy for ulceractive colitis. Six (6.7%) of the 90
      patients had short stature, i.e., a height below the 3rd centile, and 8 of the 18
      who had surgery had a subnormal height velocity, i.e., below the 25th centile for
      age at the time of surgery. Surgery was performed for resistance to medical
      therapy (n = 13) or toxic megacolon (n = 5). Surgery was followed by catch-up
      growth, i.e., increasing height velocity, in eight subjects and cessation of the
      trend of diminishing height velocity, but without catch-up growth, in five. In 11
      of the subjects who were prepubertal, the median height velocity increased from
      3.85 cm/year preoperatively to 7.35 cm/year postoperatively (p < 0.01). One year
      after surgery, 14 of the 18 patients were either asymptomatic or substantially
      improved. Surgery therefore led to improved linear growth and a prolonged symptom
      free period in most of the children and adolescents with ulcerative colitis
      undergoing this treatment.

PMID- 8576821
TI  - Reliability of short-term esophageal pH monitoring versus 24-hour study.
AB  - The child's discomfort and the cost of overnight hospitalization are clear
      disadvantages of prolonged esophageal pH monitoring. The aim of this study was to
      verify the reliability of short recording versus 24-h testing in a pediatric
      series with symptoms suggestive of gastroesophageal reflux (GER) disease. A 24-h
      pH monitoring performed on 160 patients with either gastroenterological symptoms
      (n = 61), respiratory problems (n = 58), or emesis plus respiratory problems (n =
      41) was reviewed. Regardless of clinical presentation, children were also
      classified according to age: < 12 months (n = 39), 12-71 months (n = 81), and 72
      168 months (n = 40). A diurnal fraction of 6 h, including at least 2 h after a
      meal, was compared to the entire 24-h recording in all groups with respect to the
      reflux index (RI) (sum of the periods with pH < 3.9 expressed as percentage of
      time) and reflux/h. RIs of > 10% were considered positive in patients < 1 year of
      age, whereas RIs of > 5% were considered positive in other age groups. Negative
      predictive values of the short recording RI ranged from 71 to 90%. Positive
      predictive values ranged from 50 to 83%; it was unreliable for children < 12 mos
      (50%) and patients with emesis plus respiratory problems (64%), who were,
      significantly, the youngest. Reflux/h values were not in agreement for the same
      groups. Absence of agreement was found if the absolute value of RI was
      considered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8576822
TI  - Endoscopic pneumatic reduction of an intussusception with simultaneous
      polypectomy in a child.

PMID- 8576823
TI  - Congenital fructose-glucose-galactose malabsorption.

PMID- 8576825
TI  - Object relations in abusive partner relationships: an empirical investigation.
AB  - The Social Cognition and Object Relations Scale (Westen, Barends, Leigh, Mendel,
      & Silbert, 1990) was used to assess four dimensions of object relations in the
      descriptions of relationship episodes of 41 men and 40 women entering
      psychotherapy and reporting physical abuse in their marital or partner
      relationships on the Conflict Tactics Scale (Straus, 1979) and in a matched group
      of 13 men and 13 women reporting no partner violence. Object relations levels
      were lower for men and women in the abusive relationships group. No differences
      were found between men and women in either relationship group. The findings
      provide empirical support for a hypothesis developed in the clinical literature
      of object relations impairment among both partners in abusive relationships.

PMID- 8576826
TI  - Structure of the twenty-item Toronto Alexithymia Scale.
AB  - The 20-item Toronto Alexithymia Scale (TAS-20) purportedly measures 3
      intercorrelated dimensions of the alexithymia construct: (a) difficulties
      identifying feelings (DIF), (b) difficulties describing feelings (DDF), and (c)
      externally oriented thinking (EOT). The primary purpose of this study was to
      evaluate the factor structure of the TAS-20 with full-information item factor
      analysis in 2 diverse samples: medical students (n = 219) and psychiatric
      (psychoactive substance dependent-abusing) inpatients (n = 204). In each group,
      we estimated the parameters of 1-, 2-, 3-, and 4-factor models. None of the
      various factor solutions resulted in clean, simple structures in either sample.
      In the student sample, the data were best represented (although not well) by a 3
      dimensional model: DIF, DDF, and EOT. In the psychiatric sample, however, the 3
      dimensional solution was quite different; DIF and DDF formed 1 "emotional
      awareness deficits" factor, and EOT split into 2 unrelated factors. We concluded
      that alexithymia, as measured by the TAS-20, is multidimensional and not well
      represented by a global severity score. Our recommendations include checking the
      factor structure of the TAS-20 when practicable, computing subscale scores, and
      exercising caution in interpreting TAS-20 EOT scores, particularly in
      psychoactive substance dependent-abusing inpatient samples.

PMID- 8576824
TI  - An MMPI-2 portrait of narcissism.
AB  - This study developed a Minnesota Multiphasic Personality Inventory-2 (MMPI-2)
      portrait of narcissism using the Narcissistic Personality Inventory and 5
      narcissism scales derived from the MMPI-2 with a nonclinical sample of 283
      subjects. Correlational analyses revealed a divergent pattern of relationships
      among the 16 narcissism measures and MMPI-2 scales, with 1 set of narcissism
      scales correlating positively with MMPI-2 mania (Ma) and a second set correlating
      positively with MMPI-2 depression (D), psychasthenia (Pt), feelings of
      inferiority (Sc), social introversion (Si), and other measures of distress. A
      principal-components analysis of the 6 narcissism scales produced 2 orthogonal
      factors, 1 suggesting Grandiosity and the other Depletion. High scorers on the
      Grandiosity factor were equally well characterized by a 98/89 or 96/69 MMPI-2
      profile with an average F, whereas high scorers on the Depletion factor were best
      represented by an 87/78 profile with an elevated F. Profile analyses of high
      scorers on the narcissism scales indicated that a 98/89 MMPI-2 profile with an
      elevated F score is the best overall representation of the narcissistic
      personality in nonclinical samples. Results supported 3 alternative
      interpretations, including a narcissistic continuum, narcissism as a pathological
      defense against depression and rage, and 2 forms of narcissism, 1 grandiose and
      overt and the other depleted and covert.

PMID- 8576827
TI  - Distorted self-perceptions: divergent self-reports as statistical outliers in the
      multimethod assessment of children's social-emotional adjustment.
AB  - The influence of statistical outliers among older children's self-reports was
      investigated in the context of a multitrait-multimethod validation of the
      Weinberger Adjustment Inventory (Weinberger, 1991). Self, teacher, and peer
      ratings in 6th-grade classrooms (N = 155) provided evidence of the convergent and
      discriminant validity of distress (i.e., anxiety, depression, low self-esteem,
      and low well-being) and self-restraint (i.e., impulse control, suppression of
      aggression, consideration of others, and responsibility) as superordinate
      dimensions of adjustment. However, a few children were statistical outliers whose
      self-reports starkly contradicted others' perceptions. These nonrepresentative
      cases notably affected the validity coefficients for the entire sample and seemed
      to identify children with potentially clinically significant distortions in their
      self-perceptions.

PMID- 8576828
TI  - Factor structure of the Private Self-Consciousness Scale.
AB  - Several issues concerning the factors of the Private Self-Consciousness Scale
      (PRSC) of Fenigstein et al. (1975) are examined, including possible
      artifactuality and appropriate conceptualization. Findings confirm the existence
      of the 2 factors reported in previous research (Burnkrant & Page, 1984; Lennox,
      Welch, Wolfe, Zimmerman, & Dixon, 1987; Mittal & Balasubramanian, 1987; Piliavin
      & Charng, 1988) and suggest that these factors are substantive, not artifactual,
      in nature. One factor was found to be associated with mild levels of
      psychopathology, whereas the other was not. In addition to providing a clearer
      conception of the nature of these factors, our results may help to resolve
      apparently contradictory findings in the PRSC literature. Implications for
      research on self-focused attention are also discussed.

PMID- 8576829
TI  - Concurrent validity of the MMPI-2 feminine gender role (GF) and masculine gender
      role (GM) scales.
AB  - Since the development of the revised Minnesota Multiphasic Personality Inventory
      (MMPI-2; Butcher, Dahlstrom, Graham, Tellege, & Kaemmer, 1989), no independent
      studies have been conducted to validate the new GF and GM scales, the only
      published study being based on the original standardization sample. To determine
      the concurrent validity of these scales, our study correlated GF and GM with
      scores obtained from the Bem Sex-Role Inventory, the Sex Role Behavior Scale, and
      the Sex Role Identity Scale. Because the sex-role literature has suggested
      numerous personality correlates of masculinity and femininity, the 16-PF was
      included to assess this dimension of the new scales, as well as measures of
      social desirability. Results revealed the GF and GM scales to have low internal
      consistency and low concurrent validity with established sex-role measures.
      Relative to construct validity, their patterns of correlation with personality
      measures suggest that GF and GM are more related to personality traits of
      interpersonal potency and sensitivity, respectively, than to masculinity and
      femininity. Overall, although the data yielded by these new scales provide
      additional information over Scale 5, they do not appear to hold as much promise
      as hoped for.

PMID- 8576830
TI  - Graying of the critical items: effects of aging on responding to MMPI-2 critical
      items.
AB  - The relation between age and several critical item sets on the revised Minnesota
      Multiphasic Personality Inventory (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen,
      & Kaemmer, 1989) was examined. MMPI-2 protocols from veterans entering a Veterans
      Affairs domiciliary were obtained, and the number of Grayson critical items, Koss
      Butcher critical items. Lachar-Wrobel critical items, and Caldwell critical items
      were tabulated. Another critical item set consisting of all items of the
      previously mentioned sets was also tabulated. This composite set was divided into
      a set that has items scored on Scales 1, 2, and 3, and a second set of items that
      were not scored on those three scales. The effect of age on Scales L and K was
      also studied. A one-way analysis of variance confirmed that the number of
      endorsed critical items was significantly less in older age groups, and L and K
      increased. The implication is that endorsement of a critical item may have
      increased clinical significance as a person ages.

PMID- 8576831
TI  - Internal structure of the MMPI-2 Addiction Potential Scale in alcoholic and
      psychiatric inpatients.
AB  - Recently, Weed, Butcher, McKenna, and Ben-Porath (1992) introduced two new scales
      for assessing alcohol and drug abuse with the Minnesota Multiphasic Personality
      Inventory-2 (MMPI-2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989): the
      Addiction Potential Scale (APS), an empirically derived measure similar to the
      MacAndrew Alcoholism Scale (MAC; MacAndrew, 1965), and the Addiction
      Acknowledgement Scale. Like the MAC, the APS was designed to identify the
      personality dimensions associated with substance abuse. Although there has been
      evidence to support the discriminative validity of the APS among samples of
      abusers, nonabusers, and psychiatric inpatients (Greene, Weed, Butcher,
      Arrendondo, & Davis, 1992; Weed et al., 1992), there has been no attempt to
      determine the personality dimensions tapped by the APS. Thus our study
      investigated the internal complexities of the APS. Using MMPI-2 protocols from a
      sample of alcoholic and psychiatric inpatients, we subjected the APS to a
      principal components analysis with subsequent varimax rotation. Both qualitative
      and quantitative methods were used to name the components that were identified.
      Five components consistently emerged across settings:
      Satisfaction/Dissatisfaction with Self, Powerlessness/Lack of Self-Efficacy,
      Antisocial Acting-Out, Surgency, and Risk-Taking/Recklessness, Clinical advantage
      gained from a knowledge of the internal structure of the APS was illustrated
      using 6 patients from the alcoholic sample. A rational approach to validating the
      empirical structure of the APS was discussed as a potential avenue for future
      research.

PMID- 8576832
TI  - Personality assessment and managed care.

PMID- 8576833
TI  - UCLA Loneliness Scale (Version 3): reliability, validity, and factor structure.
AB  - In this article I evaluated the psychometric properties of the UCLA Loneliness
      Scale (Version 3). Using data from prior studies of college students, nurses,
      teachers, and the elderly, analyses of the reliability, validity, and factor
      structure of this new version of the UCLA Loneliness Scale were conducted.
      Results indicated that the measure was highly reliable, both in terms of internal
      consistency (coefficient alpha ranging from .89 to .94) and test-retest
      reliability over a 1-year period (r = .73). Convergent validity for the scale was
      indicated by significant correlations with other measures of loneliness.
      Construct validity was supported by significant relations with measures of the
      adequacy of the individual's interpersonal relationships, and by correlations
      between loneliness and measures of health and well-being. Confirmatory factor
      analyses indicated that a model incorporating a global bipolar loneliness factor
      along with two method factor reflecting direction of item wording provided a very
      good fit to the data across samples. Implications of these results for future
      measurement research on loneliness are discussed.

PMID- 8576834
TI  - Racial differences on psychological measures in combat veterans seeking treatment
      for PTSD.
AB  - In this article, we examined racial differences in psychometric data on 4
      commonly used self-report inventories administered to a group of 206 combat
      veterans evaluated at a Veterans Affairs Medical Center outpatient posttraumatic
      stress disorder (PTSD) treatment program. Patients completed the Beck Depression
      Inventory, Mississippi Scale for Combat-Related PTSD, Dissociative Experiences
      Scale (DES), and Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Black
      veterans showed greater elevations than White veterans on the DES, and the F-K
      index and Scales 6 and 8 of the MMPI-2. In addition, normative data are presented
      for the entire sample on each measure. Results suggest that, consistent with
      studies using the original MMPI, these patients endorse severe levels of
      psychopathology across a broad range of symptoms, including depression and
      disturbed thinking. Implications for clinical practice and future research are
      addressed.

PMID- 8576835
TI  - Rorschach measures of posttraumatic stress in Persian Gulf War veterans: a three
      year follow-up study.
AB  - The long-term psychological effects of war-related stress were assessed with the
      Rorschach 3 years after the Persian Gulf War. Rorschach data are presented for 30
      U.S. Marine reservists at a 3-year follow-up who reported experiencing symptoms
      of posttraumatic stress (PTS) initially after Operation Desert Storm (ODS), and
      for 25 Marine reservist controls who did not participate in ODS. Results showed
      significant differences over time between the initial evaluation data and follow
      up, and between initial evaluation and the control group on selected Rorschach
      variables associated with coping ability and PTS. Scores associated with acute
      distress, capacity for coping and control, and feeling overwhelmed all were found
      to significantly decrease over time. These findings are discussed in relation to
      the assessment and understanding of PTS symptomatology over time.

PMID- 8576836
TI  - Can psychosis be malingered on the Rorschach? An empirical study.
AB  - Can psychosis be faked on the Rorschach? We examined this question by comparing 2
      groups of subjects with a high incentive to malinger, persons accused of serious
      crimes. All subjects were administered both the Minnesota Multiphasic Personality
      Inventory (MMPI) and the Rorschach and were assigned to honest (N = 35) and
      malingered (N = 13) groups on the basis of MMPI validity scales. The Rorschach
      protocols of these 2 groups were compared to assess how successfully malingerers
      could deliberately produce records that appeared psychotic on empirically derived
      Rorschach indices of psychosis. Despite an attempt to portray themselves as
      psychotic on the MMPI, subjects in the malingered group did not differ from
      honest responders on Rorschach variables that distinguish psychotic from
      nonpsychotic patients, but did differ in the number of dramatic responses
      produced. Our data suggest that the combination of the MMPI and Rorschach
      provides a powerful psychometric technique for detecting deliberate malingering
      of psychosis.

PMID- 8576837
TI  - MMPI differences among adolescent inpatients, rapists, sodomists, and sexual
      abusers.
AB  - This study examined Minnesota Multiphasic Personality Inventory (MMPI) responding
      among 61 adolescent sex offenders accused of Sexual Abuse (n = 22), Rape (n =
      19), and Sodomy (n = 18) and 15 adolescents without a history of sexual offending
      admitted to an inpatient psychiatric unit. Results indicated significant
      differences between sex offenders and inpatients as well as among sex offender
      groups on both single-scale elevations and 2-point code types. Contrary to
      previous research, adolescents in the sex offender groups demonstrated
      significantly more psychopathology than those in the inpatient sample. Subjects
      in the Sodomy group achieved the highest clinical scale elevations and were more
      likely to have scales associated with significant psychopathology as one of their
      2-point pairs. In general, increased psychopathology was associated with
      increased sexual deviancy. That is, subjects in the sexual offender groups
      evidenced more psychopathology than inpatients and the more deviant Sodomy and
      Rape groups evidenced more psychological disturbance on the MMPI than Sexual
      Abuser subjects. Results indicate that the MMPI can be useful in providing both
      quantitative and qualitative distinctions among adolescent sex offenders.

PMID- 8576838
TI  - Object relations of sexually and physically abused female children: a TAT
      analysis.
AB  - Selected Thematic Apperception Test (Murray, 1943) stories of 17 sexually abused,
      15 physically abused, and 15 nonabused but distressed clinical comparison
      subjects were analyzed using the Social Cognition and Object Relations Scales
      (Westen, Lohr, Silk, Kerber, & Goodrich, 1985). Results revealed significant
      differences in overall object relations between the abused and nonabused children
      both on mean scores, reflecting lower levels of typical functioning, and on
      frequency of Level 1 scores, indicating a propensity for more grossly
      pathological functioning. Further comparisons between sexual and physical abuse
      victims revealed differential impairments in the capacity to invest in
      relationships and moral standards. Diagnostic and theoretical implications are
      discussed.

PMID- 8576839
TI  - A general conceptual model for non-steady state pharmacokinetic/pharmacodynamic
      data.

PMID- 8576840
TI  - Bayesian design criteria: computation, comparison, and application to a
      pharmacokinetic and a pharmacodynamic model.
AB  - In this paper 3 criteria to design experiments for Bayesian estimation of the
      parameters of nonlinear models with respect to their parameters, when a prior
      distribution is available, are presented: the determinant of the Bayesian
      information matrix, the determinant of the pre-posterior covariance matrix, and
      the expected information provided by an experiment. A procedure to simplify the
      computation of these criteria is proposed in the case of continuous prior
      distributions and is compared with the criterion obtained from a linearization of
      the model about the mean of the prior distribution for the parameters. This
      procedure is applied to two models commonly encountered in the area of
      pharmacokinetics and pharmacodynamics: the one-compartment open model with bolus
      intravenous single-dose injection and the Emax model. They both involve two
      parameters. Additive as well as multiplicative gaussian measurement errors are
      considered with normal prior distributions. Various combinations of the variances
      of the prior distribution and of the measurement error are studied. Our attention
      is restricted to designs with limited numbers of measurements (1 or 2
      measurements). This situation often occurs in practice when Bayesian estimation
      is performed. The optimal Bayesian designs that result vary with the variances of
      the parameter distribution and with the measurement error. The two-point optimal
      designs sometimes differ from the D-optimal designs for the mean of the prior
      distribution and may consist of replicating measurements. For the studied cases,
      the determinant of the Bayesian information matrix and its linearized form lead
      to the same optimal designs. In some cases, the pre-posterior covariance matrix
      can be far from its lower bound, namely, the inverse of the Bayesian information
      matrix, especially for the Emax model and a multiplicative measurement error. The
      expected information provided by the experiment and the determinant of the pre
      posterior covariance matrix generally lead to the same designs except for the
      Emax model and the multiplicative measurement error. Results show that these
      criteria can be easily computed and that they could be incorporated in modules
      for designing experiments.

PMID- 8576841
TI  - Oral absorption of CGS-20625, an insoluble drug, in dogs and man.
AB  - Oral bioavailability of highly water-insoluble drugs is often quite limited and
      variable, requiring the development of improved formulations. Animal models are
      an essential aspect of the design and testing of such formulations designed to
      improve absorption in man. The present report compares the absorption of CGS
      20625, an insoluble drug, in dog and man after oral administration of the drug as
      a powder, a solid dispersion capsule, and after gastric and duodenal
      administration in PEG 400 solution. CGS-20625 powder (20 mg) given orally
      exhibited slow, delayed absorption in both dog and man, with a Cmax of 0.26 +/-
      0.07 microgram/ml at Tmax of 3 hr in dog, and 0.01 +/- 0.004 microgram/ml at 2 hr
      in man. Administration of CGS-20625 in PEG 400 solution improved absorption in
      dog and man, with a Cmax of 1.2 +/- 0.10 microgram/ml at Tmax of 0.25 hr in dog,
      and a Cmax of 0.10 +/- 0.04 microgram/ml at 0.5 hr in man. Tmax after
      administration of the hard gelatin capsule formulation was 0.9 and 1.0 hr in dog
      and man, with Cmax of 0.89 +/- 0.16 and 0.052 +/- 0.014 microgram/ml,
      respectively. Absolute bioavailability of CGS-20625 powder in the dog was 0.67 +/
      0.21, whereas the bioavailabilities of the powder and the capsule relative to
      the PEG 400 solution were 0.84 and 1.1, respectively, in dog, and 0.41 and 0.85
      respectively, in man. No significant benefits of duodenal administration were
      observed. Plasma levels were approximately 10-fold greater and oral clearance was
      approximately 5-fold less in the dog than in man. Furthermore, pharmacokinetic
      data were less variable and relative bioavailability was greater in dogs than in
      humans. Physiological factors in the gastrointestinal tract or greater first-pass
      metabolism in man may account for these species differences. The relative rate
      and extent of CGS-20625 absorption were similar between dog and man, in the order
      of powder < capsule < PEG 400 solution. In addition, in vivo absorption rates in
      both species reflect in vitro dissolution differences between the powder and the
      capsule. These data strongly support the use of the dog as a model for developing
      improved formulations of CGS-20625. Further investigation of the dog as a model
      to evaluate insoluble drug absorption is warranted.

PMID- 8576842
TI  - Population pharmacokinetics of teicoplanin in patients with endocarditis.
AB  - Teicoplanin is a new glycopeptide antibiotic, active against aerobic and
      anaerobic gram-positive bacteria. The drug is intended for the treatment of
      systemic infections including endocarditis. In two U.S. clinical safety and
      efficacy trials, loading doses of 6 to 30 mg/kg doses of teicoplanin were
      administered initially to 197 patients, followed by once-a-day treatment of
      approximately the same doses over several weeks. Blood samples were collected
      sporadically during the study to monitor serum teicoplanin concentrations either
      by FPIA or microbiological assay. Nonlinear mixed-effects modeling was performed
      on these data to characterize the population pharmacokinetics of teicoplanin that
      were best described by a two-compartment model. Patient body weight, concomitant
      gram-positive drug treatment, and serum creatinine had significant influences on
      systemic clearance (CL) of the glycopeptide. In addition, body weight affected
      the volume of distribution of the central compartment (Vc). Other demographic
      factors such as age, gender, etc., had no effects. The FPIA assay method was more
      precise than the microbiological assay.

PMID- 8576843
TI  - Determination of protein binding by in vitro charcoal adsorption.
AB  - Certain compounds such as SC-52151 have extensive nonspecific adsorption to the
      ultrafiltration devices or to dialysis membranes and therefore can not be
      measured by the conventional ultrafiltration or equilibrium dialysis methods. A
      new method based on charcoal adsorption was developed to overcome this
      difficulty. Unlike many conventional methods, which are based on the separation
      of free drug from bound drug under equilibrium conditions, the new method is
      operated under nonequilibrium conditions and involves measuring the time course
      of decline of the percentage of bound drug remaining in plasma while the free
      drug is being removed by charcoal adsorption. Theoretical aspects of the method
      and the data processing procedure are presented. SC-98A, a compound with minimal
      nonspecific adsorption to the ultrafiltration membrane, was used to demonstrate
      the applicability of this method against the ultrafiltration method. Using this
      method, the protein binding of SC-52151 in human plasma at 1.0 microgram/ml was
      determined to be in the range of 91.4-97.7% at room temperature.

PMID- 8576844
TI  - Convergence of direct and indirect pharmacodynamic response models.

PMID- 8576845
TI  - Group sequential extensions of a standard bioequivalence testing procedure.
AB  - Bioequivalence trials compare the relative bioavailability of different
      formulations of a drug. Regulatory requirements for demonstrating average
      bioequivalence of two formulations generally include showing that a (say) 90%
      confidence interval for the ratio of expected pharmacologic end point values of
      the formulations lies between specified end points, e.g., 0.8-1.25. The
      likelihood of demonstrating bioequivalence when the formulations truly are
      equivalent depends on the sample size and on the variability of the pharmacologic
      end point. Group sequential bioequivalence testing provides a statistically valid
      way to accommodate misspecification of the variability in designing the trial by
      allowing for additional observations if a clear decision to accept or reject
      bioequivalence cannot be reached with the initial set of observations. This paper
      describes group sequential bioequivalence designs applicable in most practical
      situations that allow a decision to be reached with fewer observations than fixed
      sample designs about 60% of the time at approximately the same average cost. The
      designs can be used in trials where the formulations are expected to have equal
      bioavailability and in trials where the formulations are expected to differ
      slightly. Data analyses are carried out exactly as for fixed-sample designs.
      Providing the capability of sequential decisions modestly affects the nominal
      significance levels, e.g., the required confidence level may be 93-94% instead of
      90%.

PMID- 8576846
TI  - Fitting nonlinear regression models with correlated errors to individual
      pharmacodynamic data using SAS software.
AB  - Nonlinear regression is widely used in pharmacokinetic and pharmacodynamic
      modeling by applying nonlinear ordinary least squares. Although the assumption of
      independent errors is frequently not fulfilled, this has received scant attention
      in the pharmacokinetic literature. As in linear regression, leaving correlation
      of errors out of account leads to an underestimation of the standard deviations
      of parameter estimates. On the other hand, the use of models that accommodate
      correlated errors requires more care and more computation. This paper describes a
      method to fit log-normal functions to individual response curves containing
      correlated errors by means of statistical software for time series. A sample
      computer program is given in which the SAS/ETS procedure MODEL is used. In
      particular, the problem of finding appropriate starting values for nonlinear
      iterative algorithms is considered. A linear weighted least squares approach for
      initial parameter estimation is developed. The adequacy of the method is
      investigated by means of Monte Carlo simulations. Furthermore, the statistical
      properties of nonlinear least squares with and without accommodating correlated
      errors are compared. Time action profiles of a long-acting insulin preparation
      injected subcutaneously in humans are analyzed to illustrate the usefulness of
      the method proposed.

PMID- 8576847
TI  - Focal [Ca2+]i increases detected by aequorin but not by fura-2 in histamine- and
      caffeine-stimulated swine carotid artery.
AB  - 1. We hypothesized that the homogeneity of intracellular [Ca2+] ([Ca2+]i) varies
      and is regulated in arterial smooth muscle. 2. We evaluated this hypothesis by
      exploiting the different characteristics of several [Ca2+]i indicators: (1)
      aequorin, which theoretically can measure focal increases in [Ca2+]i, (2) fura-2,
      which is predominantly a measure of mean cytoplasmic [Ca2+], and (3) myosin light
      chain phosphorylation and force, which reflect increases in [Ca2+] near the
      contractile apparatus. 3. From the differences in the observed aequorin and fura
      2 signals, we developed an index of the relative degree of [Ca2+]i homogeneity as
      the ratio of the aequorin signal and fura-2 signal. 4. Stimulation with
      intermediate concentrations of histamine (1 and 10 microM) or high [K+]o (25 and
      40 mM) increased [Ca2+]i and contractile stress. Relative [Ca2+]i homogeneity,
      estimated from the aequorin/fura-2 ratio, remained similar to levels observed in
      unstimulated tissues. 5. Higher concentrations of histamine (100 microM) also
      increased [Ca2+]i and stress, but the aequorin/fura 2 ratio declined , indicating
      increased [Ca2+]i homogeneity. Similarly, the aequorin/fura-2 ratio decreased
      when extracellular Ca2+ was removed. 6. Stimulation with histamine in low
      extracellular [Ca2+] transiently increased [Ca2+]i and the aequorin/fura-2 ratio.
      Similarly, in tissues treated with low extracellular [Ca2+], restoration of
      extracellular Ca2+ transiently increased both [Ca2+]i and the aequorin/fura-2
      ratio. Although both of these experiments demonstrated a transient decrease in
      [Ca2+]i homogeneity, only histamine stimulation led to increased myosin light
      chain phosphorylation and force. These results indicate that the focal increases
      in [Ca2+]i observed with histamine stimulation and Ca2+ restoration occurred in
      different cellular regions. 7. Addition of caffeine (20 mM) increased [Ca2+]i and
      [cAMP], but this was not accompanied by sustained increased myosin light chain
      phosphorylation or contraction. Phosphorylation of myosin light chain kinase did
      not appear to underlie the lack of increase in myosin light chain
      phosphorylation. Rather, caffeine induced a sustained increase in the
      aequorin/fura-2 ratio, suggesting that caffeine inhibits smooth muscle
      contraction by localizing increases in [Ca2+]i to a region distant from the
      contractile apparatus. 8. These data suggest that there can be transient and
      sustained focal increases in [Ca2+]i. Aequorin detected increased [Ca2+]i in
      small regions of the cytoplasm during release from and refilling of the
      intracellular Ca2+ store and with caffeine stimulation. Dual use of aequorin and
      fura-2 permits determination of relative [Ca2+]i homogeneity in smooth muscle.

PMID- 8576848
TI  - GABA transport and calcium dynamics in horizontal cells from the skate retina.
AB  - 1. Changes in intracellular calcium concentration [Ca2+]i in response to
      extracellularly applied gamma-aminobutyric acid (GABA) were studied in isolated
      horizontal cells from the all-rod skate retina. 2. Calcium measurements were made
      using fura-2 AM, both with and without whole-cell voltage clamp. Superfusion with
      GABA, in the absence of voltage clamp, resulted in an increase in [Ca2+]i; the
      threshold for detection was approximately 50 microM GABA, and a maximal response
      was elicited by 500 microM GABA. 3. The rise in [Ca2+]i was not mimicked by
      baclofen nor was it blocked by phaclofen, picrotoxin or bicuculline. However, the
      GABA-induced [Ca2+]i increase was completely abolished when extracellular sodium
      was replaced with N-methyl-D-glucamine. 4. With the horizontal cell voltage
      clamped at -70 mV, GABA evoked a large inward current, but there was no
      concomitant change in [Ca2+]i. Nifedipine, which blocks L-type voltage-gated Ca2+
      channels, suppressed the GABA-induced increase in [Ca2+]i. These findings suggest
      that the calcium response was initiated by GABA activation of sodium dependent
      electrogenic transport, and that the resultant depolarization led to the opening
      of voltage-gated Ca2+ channels, and a rise in [Ca2+]i. 5. The GABA-induced influx
      of calcium appears not to have been the sole source of the calcium increase. The
      GABA-induced rise in [Ca2+]i was reduced by dantrolene, indicating that internal
      Ca2+ stores contributed to the GABA-mediated Ca2+ response. 6. These observations
      demonstrate that activation of the GABA transporter induces changes in [Ca2+]i
      which may have important implications for the functional properties of horizontal
      cells.

PMID- 8576849
TI  - Comparison of subsarcolemmal and bulk calcium concentration during spontaneous
      calcium release in rat ventricular myocytes.
AB  - 1. The aim of these experiments was to compare the time course of changes in
      intracellular Ca2+ concentration ([Ca2+]i) measured in the bulk cytoplasm with
      those estimated to occur near the sarcolemma. Sarcolemmal Na(+)-Ca2+ exchange
      current and [Ca2+]i were measured in single, voltage-clamped ventricular
      myocytes. 2. Spontaneous Ca2+ release from the sarcoplasmic reticulum (SR)
      resulted in a transient inward current. This current developed and decayed more
      quickly than the accompanying changes in [Ca2+]i (measured with indo-1) resulting
      in a hysteresis between [Ca2+]i and current. A similar hysteresis was also
      observed if [Ca2+]i was elevated with caffeine and was removed if the current was
      low pass filtered with a time constant of 132 ms. 3. Digital video imaging (using
      fluo-3 or calcium green-1 to measure [Ca2+]i) allowed measurement of [Ca2+]i at
      all points in the cell during the wave of spontaneous Ca2+ release. The
      hysteresis between [Ca2+]i and current remained, even after allowing for the
      spatial and temporal properties of this wave. 4. The hysteresis can be accounted
      for if there is a barrier to diffusion of Ca2+ ions separating the bulk cytoplasm
      from the space under the sarcolemma (into which Ca2+ is released from the
      sarcoplasmic reticulum). The calculated subsarcolemmal [Ca2+] rises and falls
      more quickly (and reaches a higher peak) than does the bulk [Ca2+]. The delay
      introduced by this barrier is equivalent to a time constant of 133 ms. 5. The
      subsarcolemmal space described in this paper may be equivalent to the 'fuzzy
      space' previously suggested to be important in controlling SR Ca2+ release.

PMID- 8576850
TI  - Cardiac cells control transmitter release and calcium homeostasis in sympathetic
      neurons cultured from embryonic chick.
AB  - 1. The contribution of target cells in controlling the functional properties of
      sympathetic neurons was investigated using pure neuronal cultures and co-cultures
      of neurons with their physiological target cells. 2. Chick embryo sympathetic
      neurons cultured alone exhibited maximal elevation of cytosolic free Ca2+
      ([Ca2+]i) and release of tritiated noradrenaline ([3H]NA) when given ten
      stimulating pulses at 1 Hz but not at 10 Hz, yielding a negative frequency
      release response. Stimulation-evoked release was only slightly enhanced by the K+
      channel blocker tetraethylammonium (TEA, 10 mM). 3. When sympathetic neurons were
      co-cultured with cardiac cells of the chick embryo, electrically stimulated
      transmitter release and neuronal [Ca2+]i were reduced by 3- to 5-fold. Co
      cultured neurons had a positive stimulation frequency--[3H]NA release response
      and 5- to 7-fold facilitation of release by TEA. 4. Voltage-clamped Ca2+ current
      density was decreased from 0.61 +/- 0.13 pA micron-2 in neurons alone to 0.19 +/-
      0.03 pA micron-2 in co-cultured neurons. 5. Neonatal rat superior cervical
      ganglion (SCG) neurons were also relatively insensitive to TEA when cultured
      alone, but [3H]NA release was greatly facilitated by TEA when tested in SCG
      neurons co-cultured with rat neonatal cardiac myocytes. 6. The cardiac cell
      induced changes in Ca2+ handling and release properties were produced within 24 h
      by sympathetic neuroeffector cells, but not by skeletal muscle cells or sensory
      neurons, and did not occur spontaneously in neurons grown alone for up to 6 days.
      7. The frequency and TEA responses of neurons grown with cardiac cells are
      characteristic of responses seen in sympathetic neuroeffector organs. We conclude
      that physiological targets play a crucial role in development of normal
      transmitter-release properties by controlling Ca2+ homeostasis in sympathetic
      neurons.

PMID- 8576851
TI  - Calbindin-D28k: role in determining intrinsically generated firing patterns in
      rat supraoptic neurones.
AB  - 1. Physiological activation of rat supraoptic nucleus (SON) neurones leads to
      phasic firing in vasopressin neurones and fast, continuous firing in oxytocin
      neurones. Using whole-cell patch clamp methods in brain slices, we investigated
      the role of endogenous calbindin-D28k (calbindin) in determining these
      intrinsically generated patterns of firing. 2. Direct introduction of calbindin
      (0.1-0.2 mM) into twelve of twelve phasically firing neurones suppressed Ca(2+)
      dependent depolarizing after-potentials (DAPs) and changed activity from phasic
      to continuous firing. Bovine calcium binding protein (0.3 mM), an analogue of
      calbindin, had similar effects on both DAPs and firing patterns in five of five
      cells tested. 3. Introduction of anti-calbindin antiserum (1:2000-5000) into
      thirteen of thirteen continuously firing neurones unmasked DAPs and converted
      continuous into phasic firing. Such effects could not be mimicked either by
      diffusion of normal rabbit serum or antibodies directed against glial fibrillary
      acidic protein or against neurophysin. 4. Immunocytochemical staining with
      antisera directed against calbindin revealed more intense staining in the dorsal,
      oxytocin-rich and less intense staining in the ventral, vasopressin-rich areas of
      the SON. 5. Elevated intracellular Ca2+ concentration ([Ca2+]i; 0.1 mM) induced
      DAPs and phasic firing in all twenty-nine SON cells recorded. During chelation of
      intracellular Ca2+ with (1.1-11 mM) BAPTA, fifty-eight of fifty-eight neurones
      recorded displayed regular continuous activity and had no DAPs. 6. These data
      suggest that firing activities in SON cells are dependent on [Ca2+]i and that
      calbindin, acting as an endogenous Ca2+ buffer, is involved in regulation of
      intrinsic firing patterns. It is likely that calcium binding proteins have a
      similar influence on the firing patterns of many neuronal types throughout the
      nervous system.

PMID- 8576852
TI  - Voltage-dependent currents and modulation of calcium channel expression in zona
      fasciculata cells from rat adrenal gland.
AB  - 1. Whole-cell voltage-activated currents from single zona fasciculata (ZF) cells
      from rat adrenal glands were studied. T- and L-type Ca2+ currents and a slowly
      inactivating A-type K+ current were the three major currents observed. 2. In
      freshly isolated cells, the A-type K+ current and the T-type Ca2+ current were
      predominant. The A-type current was activated at -50 mV and inhibited by 4-amino
      pyridine with a half-maximal block (IC50) at 130 microM while the T-type current
      was activated at -70 mV and blocked by Cd2+, Ni2+ and amiloride with IC50 values
      of 24.1, 132.4 and 518.9 microM, respectively. 3. Under current clamp,
      depolarizing current pulses produced a single Ca2+ action potential with Cs+ in
      the pipette internal solution. Upon replacement of Cs+ by K+, the half-amplitude
      width of the action potential was shortened and membrane potential oscillations
      were seen after the spike. 4. In freshly isolated cells and during the first 24 h
      after plating, the T-type current was observed in all cells, with L-type current
      being observed in < 2% of cells, even in the presence of (+)SDZ 202,791, a
      dihydropyridine Ca2+ channel agonist. With time in culture, the T-type current
      disappeared, and a high-voltage-activated L-type current became increasingly
      apparent. In cells tested after > 2 days in culture, (+)SDZ 202,791 potentiated L
      type current by 407 +/- 12% and the antagonist (-)SDZ 202,791 blocked this
      increase. The L-type current was activated between -30 and -20 mV and was
      sensitive to nitrendipine and omega-conotoxin GVIA. 5. Pre-incubation of cultured
      ZF cells with adrenocorticotrophic hormone (ACTH) or vasoactive intestinal
      peptide (VIP) for 3 days resulted in a high, sustained level of expression of T
      type current, with a mean amplitude of 34.2 +/- 5.5 pA pF-1 for ACTH-treated
      cells compared with 3.4 +/- 1.8 pA pF-1 for untreated cells. Cycloheximide
      strongly inhibited this effect. Neither treatment affected L-type current
      expression. 6. The expression of both Ca2+ current types was unaffected by pre
      incubation with 8-bromo-cAMP or forskolin. The protein kinase A antagonist, H89,
      did not inhibit the ACTH-induced upregulation of T-type Ca2+ currents. 7. It is
      concluded that the main voltage-dependent currents involved in cell excitability
      and steroidogenesis in rat adrenal ZF cells are an A-type K+ current and a T-type
      Ca2+ current. The physiological role and control of expression of L-type Ca2+
      channels in rat ZF cells remain less clear.

PMID- 8576853
TI  - Species differences in the activity of the Na(+)-Ca2+ exchanger in mammalian
      cardiac myocytes.
AB  - 1. Species differences in the activity of the exchanger were evaluated in
      isolated myocytes from rat, guinea-pig, hamster ventricles and human atria.
      Fluorescence measurements using fura-2 were carried out in conjunction with the
      whole-cell patch-clamp technique for simultaneous recording of membrane currents
      and intracellular Ca2+ concentration. 2. Ca2+ release from sarcoplasmic reticulum
      (SR) induced either by rapid application of caffeine or by Ca2+ current elicited
      inward Na(+)-Ca2+ exchange currents (INa-Ca). The magnitude of INa-Ca was largest
      in hamster, smallest in rat, with guinea-pig and human myocytes having
      intermediate values. The ratio of caffeine-induced exchanger current densities,
      normalized with respect to the peak Ca2+ release, was 4:2:1.5:1 for hamster >
      guinea-pig > or = human > or = rat myocytes. 3. The rates of Ca2+ removal in the
      presence of caffeine, which reflect primarily the Ca2+ extruding activity of the
      Na(+)-Ca2+ exchanger, followed the same order of hamster > guinea-pig > or =
      human > or = rat. 4. The kinetics of INa-Ca vs. Ca2+ transients were different
      among species. In rat myocytes, the kinetics of the INa-Ca and the Ca2+
      transients were similar, with INa-Ca linearly proportional to intracellular Ca2+
      concentration ([Ca2+]i). In hamster myocytes, the time course of INa-Ca tracked
      only the declining phase of the Ca2+ transient with INa-Ca having faster kinetics
      during the Ca2+ release. These findings suggest that the Ca2+ concentrations in
      the vicinity of the exchanger were significantly higher than those of the cytosol
      during Ca2+ release in hamster myocytes. 5. We concluded that there are
      significant species differences in the exchanger activity of cardiac myocytes,
      arising from differences in exchanger densities, their modulation and/or their
      spatial distribution with respect to the ryanodine receptors of cardiac myocytes.

PMID- 8576854
TI  - Kinetic characterization of rat brain type IIA sodium channel alpha-subunit
      stably expressed in a somatic cell line.
AB  - 1. The rat brain type IIA Na+ channel alpha-subunit was stably expressed in
      Chinese hamster ovary (CHO) cells. Current through the expressed Na+ channels was
      studied using the whole-cell configuration of the patch clamp technique. The
      transient Na+ current was sensitive to TTX and showed a bell-shaped peak current
      vs. membrane potential relation. 2. Na+ current inactivation was better described
      by the sum of two exponentials in the potential range -30 to + 40 mV, with a
      dominating fast component and a small slower component. 3. The steady-state
      inactivation, h infinity, was related to potential by a Boltzmann distribution,
      underlying three states of the inactivation gate. 4. Recovery of the channels
      from inactivation at different potentials in the range -70 to -120 mV were
      characterized by an initial delay which decreased with hyperpolarization. The
      time course was well fitted by the sum of two exponentials. In this case the
      slower exponential was the major component, and both time constants decreased
      with hyperpolarization. 5. For a working description of the Na+ channel
      inactivation in this preparation, with a minimal deviation from the Hodgkin
      Huxley model, a three-state scheme of the form O<-->I1<-->I2 was proposed,
      replacing the original two-state scheme of the Hodgkin-Huxley model, and the rate
      constants are reported. 6. The instantaneous current-voltage relationship showed
      marked deviation from linearity and was satisfactorily fitted by the constant
      field equation. 7. The time course of activation was described by an m chi model.
      However, the best-fitted value of chi varied with the membrane potential and had
      a mean value of 2. 8. Effective gating charge was determined to be 4.7e from the
      slope of the activation plot, plotted on a logarithmic scale. 9. The rate
      constants of activation, alpha m and beta m, were determined. Their functional
      dependence on the membrane potential was investigated.

PMID- 8576855
TI  - Voltage-gated potassium currents in stratum oriens-alveus inhibitory neurones of
      the rat CA1 hippocampus.
AB  - 1. Voltage-activated K+ currents were recorded from visually identified
      inhibitory interneurones of the CA1 stratum oriens-alveus region in neonatal rat
      hippocampal slices using outside-out patch and whole-cell voltage clamp
      techniques. 2. Outward currents comprised both a transient and a sustained
      component when elicited from a holding potential of -90 mV. Tail current analysis
      of current reversal potentials showed that outward currents were carried by
      potassium ions. 3. The transient current, IA, was activated with a time to peak
      within 5 ms, inactivated with a time constant of approximately 15 ms at 0 mV and
      possessed half-activation at -14 mV. Half-inactivation of the transient current
      occurred at -71 mV. At -90 mV, the transient current recovered from inactivation
      with a time constant of 142 ms. 4. Activation of currents from a holding
      potential of -50 mV permitted isolation of the sustained current, IK. In Ca(2+)
      free conditions the sustained current showed rapid activation, reaching about 80%
      of its maximum within 1.5 ms, and showed little inactivation during 1 s
      depolarizing steps. The majority of sustained outward currents showed no voltage
      dependent inactivation. In approximately 20% of cells, a slow time-dependent
      inactivation of the sustained current was observed, suggesting the presence of a
      second type of sustained current in these cells. 5. A Ca(2+)-dependent K+ current
      comprised a significant portion of the total sustained current; this current was
      activated at voltages positive to -30 mV and showed no time-dependent
      inactivation over a 1 s depolarizing step. This current component was removed in
      Ca(2+)-free conditions or by iberiotoxin. 6. Low concentrations of 4-AP (50
      microM) attenuated both the transient and sustained current components recorded
      in a Ca(2+)-free solution. Higher concentrations of 4-AP (< 10 mM) were without
      further effect on the sustained current but completely blocked the transient
      current with an IC50 of 1.8 mM. TEA blocked the sustained current with an IC50 of
      7.9 mM without significantly reducing the transient current. Both current
      components were resistant to dendrotoxin (500 nM).

PMID- 8576856
TI  - Potassium conductances underlying repolarization and after-hyperpolarization in
      rat CA1 hippocampal interneurones.
AB  - 1. The roles of multiple potassium conductances underlying action potential
      repolarization and after-hyperpolarization (AHP) in visually identified st.
      oriens-alveus (st. O-A) inhibitory interneurones of neonatal rat CA1 hippocampal
      slices were determined using whole-cell patch clamp techniques. 2. 4
      Aminopyridine dose-dependently prolonged the action potential repolarization. The
      effects of 4-AP persisted in Ca(2+)-free conditions. Action potentials evoked
      from hyperpolarized potentials possessed an increased rate of repolarization.
      These data suggest an involvement of the rapidly activating transient current,
      IA, in spike repolarization. 3. Action potential duration was increased in the
      presence of Ca(2+)-free, Cd(2+)-containing solution, iberiotoxin or 1 mM TEA. The
      fast component of the AHP was attenuated by these agents suggesting that the
      Ca(2+)-activated K+ conductance, IC, underlies both the spike repolarization and
      fast AHP. 4. In Ca(2+)-free conditions, TEA (> 1 mM) dose-dependently prolonged
      the action potential duration by blocking a late conductance in action potential
      repolarization, suggesting a role for the sustained current, IK. 5. The slow AHP
      was attenuated by Ca(2+)-free medium, apamin or the Ca2+ chelator EGTA,
      suggesting a role for the Ca(2+)-activated K+ conductance, IAHP. 6. We conclude
      that action potential repolarization and AHP of st. O-A interneurones result from
      the activation of pharmacologically distinct, temporally overlapping potassium
      conductances. These findings are discussed with reference to the voltage clamp
      data presented in the preceding manuscript.

PMID- 8576857
TI  - Thyroid status and diabetes modulate regional differences in potassium currents
      in rat ventricle.
AB  - 1. The rate dependence and recovery kinetics of the Ca(2+)-independent transient
      (I(t)) and steady-state or 'pedestal' (Iss) outward potassium (K+) currents were
      studied in single myocytes isolated from epicardial and endocardial regions of
      rat left ventricles. The whole-cell, suction microelectrode method was used to
      measure baseline (fully reactivated) I(t), as well as its rate-dependent
      attenuation. Results from a group of control animals were compared with data from
      three other groups having an experimentally altered hormonal status. 2. I(t) was
      significantly smaller in endocardial cells than in epicardial cells, in part due
      to a very large difference in the recovery kinetics of this current in
      endocardial cells. This was reflected in a pronounced rate-dependent prolongation
      of endocardial action potentials. In contrast, the non-inactivating 'pedestal'
      current, Iss, was very similar in magnitude and showed comparable rate dependence
      in cells from both epicardium and endocardium. 3. Changing the thyroid status had
      selective, differential actions on the amplitude and rate dependence of It in
      epicardial and endocardial cells. Under hypothyroid conditions there was a more
      pronounced reduction of baseline I(t) in epicardial than in endocardial cells.
      Moreover, a slowing of the recovery kinetics in epicardial cells resulted in an
      enhanced attenuation of this current at high rates. Changing thyroid status had
      no effect on the magnitude or rate dependence of Iss in cells from either region
      of the left ventricle. 4. Following establishment of hyperthyroid conditions,
      there was no significant change in I(t) magnitude at baseline. However, when
      compared with control data, the recovery of I(t) was considerably faster in
      endocardial cells, and marginally faster in epicardial cells. 5. Streptozotocin
      induced diabetic conditions resulted in a much greater attenuation of I(t) in
      epicardial cells than in endocardial cells. Epicardial action potentials in these
      conditions showed prominent rate-dependent prolongation. Iss was reduced to a
      similar extent in cells from these two regions. 6. Our findings demonstrate that
      altered hormonal status can selectively change the amplitude and kinetics of It
      in the epi- and endocardium of rat left ventricle. These changes can reduce the
      epicardial-endocardial gradients in the magnitude and recovery kinetics of It and
      hence diminish the intrinsic differences in both action potential duration and
      refractoriness.

PMID- 8576858
TI  - A voltage-gated chloride channel in ascidian embryos modulated by both the cell
      cycle clock and cell volume.
AB  - 1. Eggs of the ascidian Boltenia villosa have an inwardly rectifying Cl- current
      whose amplitude varies by more than 10-fold during each cell cycle, the largest
      amplitude being at exit from M-phase. We examined whether this current was also
      sensitive to changes in cell volume. 2. Cell swelling, produced by direct
      inflation through a whole-cell recording pipette, greatly increased the amplitude
      of the Cl- current at all stages of the cell cycle in activated eggs. Swelling
      was much less effective in unfertilized eggs. 3. The increase in Cl- current
      amplitude continued for 10-20 min after an increase in diameter that was complete
      in 10 s, suggesting the involvement of a second messenger system in the response.
      4. Treatment of unfertilized eggs with 6-dimethylaminopurine (DMAP), an inhibitor
      of cell cycle-dependent protein kinases, increased the amplitude of the Cl-
      current and its sensitivity to swelling to levels characteristic of fertilized
      eggs. 5. Osmotically produced swelling also increased Cl- current amplitude in
      unfertilized eggs. 6. We propose that dephosphorylation renders the Cl- channel
      functional, and that swelling or activation of the egg increases the sensitivity
      of the channel to dephosphorylation, perhaps by disrupting its links to the
      cytoskeleton.

PMID- 8576859
TI  - Electrophysiological differences between oxytocin and vasopressin neurones
      recorded from female rats in vitro.
AB  - 1. Intracellular recordings in vitro from immunochemically identified oxytocin
      (OT) and vasopressin (VP) neurones in the supraoptic nucleus (SON) of virgin or
      lactating female rats revealed no differences between neurone types in membrane
      potential (Vm), input resistance and current-voltage relationships (I-V), when
      taken at resting membrane potentials. 2. When OT (94%), but not VP, neurones
      (93%) were current clamped at depolarized voltages (above -50 mV), small
      hyperpolarizing pulses revealed a time- and voltage-dependent outward
      rectification that was present above -75 mV and that decreased in amplitude as Vm
      approached the equilibrium potential for potassium (EK). The rectification was
      more pronounced when the neurones were held at a more depolarized membrane
      potential, and was larger the longer the neurone was held depolarized, reaching a
      maximum at 0.6-0.9 s. 3. A rebound depolarization followed the offset of
      hyperpolarizing pulses that were associated with the rectification. The peak
      amplitude of the rebound showed a time and a voltage dependence. It followed a
      bell-shaped curve as the hyperpolarizing commands were made larger, attaining a
      peak at -65 +/- 1.5 mV. The rebound amplitude increased with pulse duration,
      achieving a half-maximal amplitude at 0.5 +/- 0.1 s. 4. The expression of the
      sustained outward rectification and the rebound in OT neurones was similar in
      virgin and lactating female rats. 5. These results indicate the presence of
      significant differences in the intrinsic membrane properties, probably K+
      currents, between OT and VP neurones in both lactating and virgin female rats.

PMID- 8576861
TI  - Specific motifs in the external loops of connexin proteins can determine gap
      junction formation between chick heart myocytes.
AB  - 1. Gap junction formation was compared in the absence and presence of small
      peptides containing extracellular loop sequences of gap junction (connexin)
      proteins by measuring the time taken for pairs of spontaneously beating embryonic
      chick heart myoballs to synchronize beat rates. Test peptides were derived from
      connexin 32. Non-homologous peptides were used as controls. Control pairs took 42
      +/- 0.5 min (mean +/- S.E.M.; n = 1088) to synchronize. 2. Connexins 32 and 43,
      but not 26, were detected in gap junction plaques. The density and distribution
      of connexin immunolabelling varied between myoballs. 3. Peptides containing
      conserved motifs from extracellular loops 1 and 2 delayed gap junction formation.
      The steep portion of the dose-response relation lay between 30 and 300 microM
      peptide. 4. In loop 1, the conserved motifs QPG and SHVR were identified as being
      involved in junction formation. In loop 2, the conserved SRPTEK motif was
      important. The ability of peptides containing the SRPTEK motif to interfere with
      the formation of gap junctions was enhanced by amino acids from the putative
      membrane-spanning region. 5. Peptides from loop 1 and loop 2 were equivalently
      effective; there was no synergism between them. 6. The inclusion of conserved
      cysteines in test peptides did not make them more effective in the competition
      assay.

PMID- 8576860
TI  - Regional difference in the distribution of L-NAME-sensitive and -insensitive NANC
      relaxations in cat airway.
AB  - 1. To investigate the distribution profile of functional inhibitory non
      adrenergic non-cholinergic (i-NANC) nerves and the contribution of NO to the NANC
      relaxation in the cat, we studied the effects of N omega-nitro-L-arginine methyl
      ester (L-NAME) on NANC relaxation elicited by electrical field stimulation (EFS)
      in the trachea, bronchus and bronchiole. 2. EFS applied to the tracheal smooth
      muscle during contraction induced by 5-HT (10(-5) M) in the presence of atropine
      (10(-6) M) and guanethidine (10(-6) M) elicited a monophasic NANC relaxation. By
      contrast, NANC relaxation elicited in the peripheral airway was biphasic,
      comprising an initial fast followed by a second slow component and L-NAME (10(-5)
      M) selectively abolished the first component without affecting the second one. In
      the trachea, L-NAME (10(-5) M) completely suppressed the monophasic NANC
      relaxation when single or short repetitive stimuli (< 5) with 1 ms pulse duration
      were applied. However, at higher repetitive stimuli (> 10) with 1 or 4 ms pulse
      duration, suppression of NANC relaxation was incomplete. 3. In the small bronchi
      obtained from L-NAME-pretreated cats, EFS applied during contraction induced by 5
      HT (10(-5) M) elicited only the slow component of NANC relaxation which is
      sensitive to tetrodotoxin. 4. In the peripheral airway, a newly synthesized VIP
      antagonist (10(-6) M) or alpha-chymotrypsin (1 U ml-1) considerably attenuated
      the amplitude of L-NAME-insensitive relaxation. 5. Single or repetitive EFS
      consistently evoked excitatory junction potentials (EJPs) in the central and
      peripheral airways. When tissues were exposed to atropine (10(-6) M) and
      guanethidine (10(-6) M), single or repetitive EFS did not alter the resting
      membrane potential. 6. These results indicate that at least two
      neurotransmitters, possibly NO or NO-containing compounds and VIP, are involved
      in i-NANC neurotransmission and the distribution profile of the two components
      differs in the central and peripheral airway of the cat.

PMID- 8576862
TI  - Dependence of force on length at constant cross-bridge phosphorylation in the
      swine carotid media.
AB  - 1. The dependence of force (F) on length (L) in smooth muscle remains uncertain
      since (i) it is influenced by changes in activation (myosin light chain
      phosphorylation), (ii) no anatomical reference length for the contractile unit is
      available, (iii) the length at which optimum force is generated (L(o)) exhibits a
      broad, flat optimum, and (iv) the presence of an extensive connective tissue
      network makes it difficult to stretch tissues without damage. 2. A swine carotid
      medial ring preparation prepared by removal of the adventitia and endothelium
      could be stretched to 1.8 L(o) without decreasing active force generation on
      return to shorter lengths. 3. A highly reproducible mechanically defined
      reference length, L(o), was obtained by fitting force-length data between 0.3 and
      1.6 L(o) with a third-order polynomial where L = L(o) when dF/dL = 0. 4.
      Activation as assessed by myosin regulatory light chain (MRLC) phosphorylation
      increased with length in 100 microM histamine-stimulated tissues from 0.6 to 1.8
      L(o). 5. Activation was constant in K(+)-depolarized and field-stimulated tissues
      from 1.0 to 1.8 L(o) allowing determination of the descending limb of the force
      length relation to be assessed independently of activation. 6. The slope of the
      descending limb of the force-length relation was linear except at very long
      lengths, which often produced tissue damage. The slope was not statistically
      different from that estimated for sarcomeres in vertebrate skeletal muscle. 7.
      The medial ring preparation and the procedures used to define the reference
      length provide advantages for the measurement of length-dependent variables.

PMID- 8576863
TI  - Fatigue and heat production in repeated contractions of mouse skeletal muscle.
AB  - 1. This study tested the hypothesis that moderate fatigue of skeletal muscle
      arises from a mismatch between energy demand and energy supply. Fatigue was
      defined as the decline in isometric force. Energy supply and demand were assessed
      from measurements of muscle heat production. 2. Experiments were performed in
      vitro (21 degrees C) with bundles of muscle fibres from mouse fast-twitch
      extensor digitorum longus muscle and slow-twitch soleus muscle. Fibre bundles
      were fatigued using a series of thirty isometric tetani. Cycle duration (time
      between successive tetani) was 5 s. The amount of fatigue that occurred during a
      series of tetani was varied by varying contraction duty cycle (tetanus
      duration/cycle duration) by varying tetanus duration. 3. Peak isometric force and
      total heat production in each cycle were measured. For each cycle, the amounts of
      initial heat (H(i)) and recovery heat (Hr) produced were calculated and used as
      indices of energy use and supply, respectively. H(i) and Hr were used to estimate
      the net initial chemical breakdown (in energy units) in each cycle (H(i,net)). 4.
      The magnitude of H(i,net) was greatest in the early stages of the contraction
      protocol when Hr was still increasing towards a steady value. The magnitude of
      decline in force between successive tetani was proportional to H(i,net) for both
      muscles. 5. The results are consistent with the idea that the development of
      moderate levels of fatigue at the start of a series of contractions is due to the
      rate of energy supply being inadequate to match the rate of energy use.

PMID- 8576864
TI  - Mesenteric blood pressure profile of conscious, freely moving rats.
AB  - 1. Blood pressure has been measured in the aorta and at four points in the
      mesenteric circulation of conscious, freely moving rats under physiological,
      resting conditions. 2. Using small polythene catheters, blood pressure was
      measured simultaneously in the aorta and either distally in the superior
      mesenteric artery (group A), at the base of a mesenteric arterial arcade (vessel
      diameter ca 100 microns) (group B), at the base of a mesenteric venous arcade
      (group C) or distally in the superior mesenteric vein (group D). Local blood flow
      distribution proximal and distal to the measurement point was restored after the
      cannulations through appropriate ligations. 3. In conscious animals 5-17 h after
      surgery, systemic mean blood pressure was 121 +/- 2 mmHg. Local pressures at the
      four locations (as a percentage of systemic pressure) were: 95 +/- 1% in group A,
      64 +/- 2% in group B, 13 +/- 1% in group C and 7 +/- 1% in group D. Thus, large
      arteries dissipated 5% of the total pressure drop, arcade small arteries 31%, the
      intramural circulation 51%, arcade veins 6% and the remaining veins plus the
      hepatic circulation 7%. 4. Immediately after surgery, the corresponding pressure
      drops were 4, 16, 66, 5 and 9%, respectively, thus emphasizing that the pressure
      profile can be profoundly affected by surgery and anaesthesia. 5. The data
      indicate that under resting conditions in conscious, freely moving rats, half the
      mesenteric vascular resistance resides outside the intramural circulation,
      primarily in the arcade small arteries.

PMID- 8576865
TI  - Adenosine mediates metabolic and cardiovascular responses to hypoxia in fetal
      sheep.
AB  - 1. In seven unanaesthetized fetal sheep (> 80% term), isocapnic hypoxia (arterial
      partial pressure of O2, Pa,O2, approximately 15 mmHg) was induced for 1 h by
      lowering maternal inspired PO2. Fetal hypoxia was also produced during intra
      arterial administration of the adenosine receptor antagonist 8-(p-sulphophenyl)
      theophylline (8-SPT). The fetal 8-SPT infusion was begun just prior to hypoxia
      and was stopped when fetal Pa,O2 was returned to normal. 2. Hypoxia induced a
      progressive fetal acidosis, a rise in mean arterial pressure, a transient fall in
      heart rate and a decrease in breathing movements. 8-SPT significantly reduced the
      metabolic acidosis and abolished the hypertension and bradycardia without
      altering hypoxic inhibition of fetal breathing. Administration of the vehicle for
      8-SPT during hypoxia did not significantly affect the normal fetal metabolic and
      cardiovascular responses to acute O2 deprivation. 3. It is concluded that
      adenosine mediates the fetal bradycardia and hypertension produced by hypoxia,
      indicating that adenosine modulates fetal autonomic responses to acute oxygen
      deficiency. Secondly, adenosine contributes to fetal metabolic acidaemia,
      suggesting that adenosine also modulates fetal glycolytic responses to hypoxia.

PMID- 8576866
TI  - Carbonic anhydrase and control of breathing: different effects of benzolamide and
      methazolamide in the anaesthetized cat.
AB  - 1. The effect of inhibition of erythrocyte carbonic anhydrase on the ventilatory
      response to CO2 was studied by administering benzolamide (70 mg kg-1, i.v.), an
      inhibitor which does not cross the blood-brain barrier, to carotid body
      denervated cats which were anaesthetized with chloralose-urethane. 2. In the same
      animals the effect on the ventilatory response to CO2 of subsequent inhibition of
      central nervous system (CNS) carbonic anhydrase was studied by infusing
      methazolamide (20 mg kg-1), an inhibitor which rapidly penetrates into brain
      tissue. 3. The results show that inhibition of erythrocyte carbonic anhydrase by
      benzolamide leads to a decrease in the slope of the normoxic CO2 response curve,
      and a decrease of the extrapolated arterial PCO2 at zero ventilation. 4.
      Inhibition of CNS carbonic anhydrase by methazolamide results in an increase in
      slope and alpha-intercept of the ventilatory CO2 response curve. 5. Using a mass
      balance equation for CO2 of a brain compartment, it is argued that inhibition of
      erythrocyte carbonic anhydrase results in a decrease in slope of the in vivo CO2
      dissociation curve, which can explain the effects of benzolamide. 6. The changes
      in slope and intercept induced by methazolamide are discussed in relation to
      effects on neurones containing carbonic anhydrase, which may include central
      chemoreceptors.

PMID- 8576867
TI  - Thermogenesis associated with spontaneous activity: an important component of
      thermoregulatory needs in rats.
AB  - 1. Quantification of the energy cost of spontaneous activity in freely moving
      lean and obese Zucker rats was performed at 28 degrees C and during acute cold
      exposure (from 28 to 5 degrees C). 2. An open-circuit metabolic chamber was
      supplemented with an ultrasensitive ergometric platform equipped with six
      undirectional accelerometers and with an opto-electronic device for location of
      the rat's centre of mass. 3. Resting and mean metabolic rates during control and
      cold-exposure periods were similar in both groups of rats. The 'extra
      thermogenesis' (ET), i.e. the difference between mean and resting metabolic rate,
      amounted to 11.7 +/- 1.1 and 8.6 +/- 0.7% of resting metabolic rate at 28 degrees
      C, and 39.7 +/- 2.9 and 34.1 +/- 2.9% of resting metabolic rate during cold
      exposure for lean and obese rats, respectively. 4. During the control period
      obese rats moved 3.71 +/- 0.61 m h-1 and lean rats 8.69 +/- 0.57 m h-1, but
      during cold exposure the distance moved by obese rats increased 3.58 +/- 0.33
      fold whereas that moved by lean rats only increased 1.40 +/- 0.06-fold. The
      external work performed during spontaneous activity seldom reached 1.0% of the
      increase in metabolic rate. 5. In obese rats, weight was a good predictor of the
      distance covered, and cold exposure induced the same percentage increase in both
      distance and ET. Activity-associated thermogenesis of obese rats was the
      predominant thermogenic source that substituted for their atrophied brown fat
      thermogenesis whereas in lean rats with active brown fat these correlations were
      not found.

PMID- 8576868
TI  - A study of the role of corticosterone as a mediator in exercise-induced
      stimulation of murine macrophage phagocytosis.
AB  - 1. It is generally accepted that physical activity provokes changes in the immune
      system. Previous studies have demonstrated that the stress of physical activity
      (swimming until exhaustion) increases the phagocytic activity of peritoneal
      macrophages. However, the precise mechanisms remain unknown. 2. Two experiments
      were performed in the present study. (A) Peritoneal macrophages from control mice
      were incubated with plasma from three different groups of mice: (1) mice
      subjected to swimming until exhaustion with no previous training, (2) mice
      subjected to the same activity but with 1 month of training (30 min day-1), and
      (3) a control (non-exercised) group. The differences in the resulting phagocytic
      (attachment and ingestion) capacity were measured. (B) Changes in the
      concentration of plasma corticosterone after exercise were also measured, and the
      effect of incubation with the postexercise plasma corticosterone level on the
      phagocytic activity of peritoneal macrophages was then studied in vitro. 3. The
      results were: (A) incubation with plasma from both groups of exercised mice (with
      and without previous training) led to increased levels of phagocytic capacity
      (number of C. albicans cells ingested per 100 macrophages). (B) Incubation with a
      corticosterone concentration of 0.72 mumol l-1 (similar to that observed in
      plasma immediately after exercise) raised the phagocytic capacity (144 +/- 12
      after incubation with 0.72 mumol l-1 vs. 93 +/- 19 after incubation with 0.24
      mumol l-1). This increase was also significantly greater than that observed with
      7.2 mumol l-1 corticosterone. 4. It is concluded that corticosterone may mediate
      the increased phagocytic function of peritoneal macrophages induced by exercise.

PMID- 8576869
TI  - Task-related variation in corticospinal output evoked by transcranial magnetic
      stimulation in the macaque monkey.
AB  - 1. A volley evoked by transcranial magnetic stimulation (TMS) over the motor
      cortex was recorded from the medullary pyramid in an awake monkey performing a
      precision grip task. It was identified as corticospinal using a collision test.
      2. The volley latency was 0.50 ms, indicating that it was produced by direct
      activation of corticospinal neurones. 3. A mean modulation of 13% in the
      amplitude of this volley was seen during task performance, with the largest
      volley occurring during the hold phase of the task. A similar pattern of
      modulation was seen in the EMG responses of hand and forearm muscles to TMS. 4.
      No comparable modulation was observed in a volley evoked by electrical
      stimulation of the corticospinal fibres via chronically implanted electrodes in
      the cerebral peduncle. 5. The results are compatible with direct activation of
      the corticospinal neurones by TMS at a site close to the soma, with the
      probability of activation by TMS depending on the current level of cortical
      excitability.

PMID- 8576870
TI  - Influence of hypoxic duration and posthypoxic inspired O2 concentration on short
      term potentiation of breathing in humans.
AB  - 1. Short term potentiation (STP) of breathing refers to respiratory activity at a
      higher level than expected just from the dynamics of the peripheral and central
      chemoreceptors. In humans STP is activated by hypoxic stimulation. 2. To
      investigate the effects of the duration of hypoxia and the posthypoxic inspired
      O2 concentration on STP, the ventilatory responses to 30 s and 1, 3 and 5 min of
      hypoxia (end-tidal PO2, P(ET.O2) approximately 6.5 kPa) followed by normoxia
      (P(ET.O2) approximately 14.5 kPa) and hyperoxia (P(ET.O2) approximately 70 kPa)
      were studied in ten healthy subjects. End-tidal PCO2 (P(ET.CO2)) was clamped
      during hypoxic and recovery periods at 5.7 kPa. 3. Steady-state ventilation (VE)
      was 13.7 +/- 0.6 l min-1 during normoxia and increased to 15.5 +/- 0.3 l min-1
      during hyperoxia (P < 0.05) due to the reduced Haldane effect and some decrease
      in cerebral blood flow (CBF). 4. The mean responses following hypoxia reached
      normoxic baseline after 69, 54, 12 and 12 s when 30 s and 1, 3 and 5 min of
      hypoxia, respectively, were followed by normoxia. An undershoot of 10 and 20%
      below hyperoxic baseline was observed when 3 and 5 min of hypoxia, respectively,
      were followed by hyperoxia. Hyperoxic VE reached hyperoxic baseline after 9, 15,
      12 and 9 s at the termination of 30 s and 1, 3 and 5 min of hypoxia,
      respectively. 5. Normoxic recovery from 30 s and 1 min of hypoxia displayed a
      fast and subsequent slow decrease towards normoxic baseline. The fast component
      was attributed to the loss of the hypoxic drive at the site of the peripheral
      chemoreceptors, and the slow component to the decay of the STP that had been
      activated centrally by the stimulus. A slow decrease at the termination of 30 s
      and 1 min of hypoxia by hyperoxia was not observed since this component was
      cancelled by the increase in ventilatory output due to the reduced Haldane effect
      and some decrease of CBF. 6. Decay of the STP was not apparent in the normoxic
      recovery from 3 and 5 min of hypoxia as a slow component since it cancelled
      against the slow ventilatory increase related to the increase of brain tissue
      PCO2 due to the reduction of CBF at the relief of hypoxia. The undershoot
      observed when hyperoxia followed 3 and 5 min of hypoxia reflects the stimulatory
      effects of hyperoxia on VE. 7. The manifestation of the STP as a slow ventilatory
      decrease depends on the duration of hypoxia and the subsequent inspired oxygen
      concentration. We argue that STP is not abolished by the central depressive
      effects of hypoxia, although the manifestation of the STP may be overridden or
      counteracted by other mechanisms.

PMID- 8576871
TI  - The metabolic costs of different types of contractile activity of the human
      adductor pollicis muscle.
AB  - 1. The metabolic costs and physiological consequences of shortening contractions
      of a human muscle working in situ have been compared with those of the muscle
      maintaining a continuous isometric contraction and when performing repeated brief
      isometric contractions. 2. After a total of 10 s stimulation, the shortening and
      intermittent brief isometric protocols had very similar effects, causing a 30%
      loss of force and a threefold increase in the half-time of relaxation. This was
      in contrast to the continuous isometric contraction protocol where there was less
      than 10% loss of force or slowing of relaxation. 3. The ATP cost over the first 5
      s of the continuous isometric protocol was 27 mmol (l intracellular water)-1
      while for the shortening and repeated brief isometric protocols the costs were 48
      and 46 mmol (l intracellular water)-1, respectively. 4. The results show that
      shortening and repeated brief isometric contractions are considerably more
      energetically demanding, and hence more fatiguing, than sustained isometric
      contractions.

PMID- 8576872
TI  - Ipsilateral cortical stimulation inhibited the long-latency response to stretch
      in the long finger flexors in humans.
AB  - 1. Transcranial magnetic stimulation over the motor cortex of one hemisphere is
      known to decrease the excitability of the motor cortex of the other hemisphere.
      We investigated the effect of this interhemispheric or transcallosal inhibition
      of the motor cortex on the reflex response to stretch in the long flexors of the
      fingers in human subjects. 2. Stretch of the long finger flexors, through
      extension of the proximal interphalangeal joints with a torque pulse, resulted in
      a reflex EMG response with short- and long-latency components. Magnetic
      stimulation was applied over the motor cortex ipsilateral to the muscles being
      stretched. When a magnetic shock but not stretch was given, a decrease in
      background EMG in the ipsilateral finger flexors occurred at a latency of 33 +/-
      6.2 ms after the stimulus and with a duration of 25 +/- 8.5 ms. 3. If the
      magnetic shock and the stretch were given at appropriate interstimulus intervals,
      the long-latency stretch reflex (LLSR) showed inhibition in all subjects. LLSR
      was reduced to 49.2 +/- 19% (S.D.; n = 9) of the area of the control response. 4.
      The LLSR did not act as a single event in response to the magnetic shock. That
      is, part of the LLSR could be reduced in amplitude while the remainder was
      unaffected. The reduction in LLSR had an onset latency of 27 +/- 3.8 ms after the
      magnetic stimulus and a duration of 29-55 ms. Inhibition was only obvious when
      this interval after the magnetic stimulus coincided with the LLSR. 5. In most
      subjects the short-latency stretch reflex (SLSR) also showed some inhibition
      (83.4 +/- 11.2% of the control). However, this was less than the effect on the
      LLSR in all subjects. 6. The site of stimulation, over the ipsilateral motor
      cortex, was specific for inhibition of the LLSR. When the coil was moved
      anteriorly or to the midline, inhibition was significantly decreased. 7. We
      suggest that the inhibition of the LLSR of the long flexors of the fingers
      resulted from a reduction in excitability of the motor cortex produced by an
      inhibitory transcallosal pathway and conclude that the LLSR in this muscle has a
      transcortical component.

PMID- 8576873
TI  - Increased resting discharge of human spindle afferents following voluntary
      contractions.
AB  - 1. The aim of this study was to assess the incidence of lasting alterations in
      discharge rate of muscle spindle afferents innervating human ankle and toe
      dorsiflexor muscles following isometric contractions. 2. The subjects performed
      controlled isometric ankle dorsiflexions maintained for approximately 5 s. During
      the contraction the discharge of all but one spindle afferent increased above the
      precontraction level. After complete relaxation, there was prolonged enhancement
      of the discharge rate of nineteen of fifty-five muscle spindle afferents and none
      of three Golgi tendon organ afferents. Ten of the nineteen spindle afferents had
      been silent prior to the contraction. For the population of fifty-five spindle
      afferents, the mean 'postcontraction' discharge rate was 65% higher than the mean
      precontraction discharge rate, with the mean rate increasing from 2.3 to 3.9 Hz
      (P < 0.001). The mean duration of the enhanced postcontraction discharge was 52 s
      (range, 8-240 s). 3. Stretch applied to the tendon of the receptor-bearing muscle
      in twelve of fourteen spindle afferents with an enhanced postcontraction
      discharge rate eliminated or reduced the enhanced discharge rate. 4. The high
      incidence of an enhanced spindle discharge after voluntary contraction (35% of
      spindle afferents) suggests that muscle 'history' should be taken into account
      when interpreting changes in spindle discharge rates. The enhanced discharge
      rates following contraction probably reflect a long-lasting effect of the
      contraction-associated increase in fusimotor drive on intrafusal stiffness,
      rather than the persistence of fusimotor drive following relaxation.

PMID- 8576874
TI  - Lateral hemostatic sutures in cold knife conization of the cervix. What do they
      accomplish?
AB  - OBJECTIVE: The purpose of cold knife conization is to ligate the descending
      cervical branch of the uterine artery and thus to decrease bleeding. The aim of
      this study was to investigate the actual frequency of ligation. STUDY DESIGN: Two
      lateral sutures were placed in the cervix at the 3 and 9 o'clock positions in 97
      patients (194 sutures) as part of vaginal hysterectomy. The position of each
      suture was determined during evaluation of the surgical specimen. RESULTS:
      Because the specimens from 10 patients contained only single sutures, only 184
      sutures were actually evaluated. Upon microscopic examination, 50 of the 184
      (27%) appeared to contain no artery. Of the remaining 134 sutures, 95 (71%)
      enclosed an artery, and 9 (7%) lay within a 10 x field of a branch. Only 30
      sutures (22%) missed the artery entirely. Thus, in the 73% of cases where an
      artery of significant size could be identified, the artery lay within a lateral
      stitch 71% of the time. CONCLUSION: If the descending cervical branch of the
      uterine artery supplies most of the blood to the cervix, advance placement of
      lateral sutures would be expected to reduce blood loss during conization.

PMID- 8576875
TI  - Open study of topical 0.025% tretinoin in the treatment of vulvar lichen
      sclerosus. One year of therapy.
AB  - OBJECTIVE: To study the use of topical tretinoin for treating vulvar lichen
      sclerosus. STUDY DESIGN: An open, uncontrolled clinical study on 22 patients
      affected by histologically confirmed vulvar lichen sclerosus. Topical 0.025%
      tretinoin was applied once a day, five days a week, for one year. Clinical and
      histologic parameters were evaluated before and after therapy, and statistical
      analysis was performed. RESULTS: Symptoms, gross appearance and histopathologic
      features improved in a highly significant manner (P < .001). Cutaneous side
      effects were observed but rapidly disappeared, and no patient left the study for
      this reason. Maintenance of results was observed at the 4-13-month follow-up
      visits. CONCLUSION: Topical tretinoin seems feasible for use in the topical
      treatment of vulvar lichen sclerosus.

PMID- 8576876
TI  - Variability of day 3 follicle-stimulating hormone levels in eumenorrheic women.
AB  - OBJECTIVE: To assess the intercycle variability of early follicular follicle
      stimulating hormone (FSH) and estradiol (E2) levels in eumenorrheic women
      according to age. STUDY DESIGN: Forty-eight female volunteers with regular
      menstrual cycles were studied. Serum samples were obtained on cycle day 3 in
      multiple cycles over a one-year period. Serum was also obtained on consecutive
      cycle days 2, 3 or 4 in a single cycle in 20 participants. All samples were
      assayed for FSH and E2 by radioimmunoassay. RESULTS: In women under 40 years of
      age, all initial day 3 FSH levels were < 20 mIU/mL, and 15% of subjects had a
      subsequently elevated day 3 FSH level (> or = 20 mIU/mL) within the year. In
      eight women 40-44 years of age, 75% had an initial day 3 FSH level < 20 mIU/mL,
      but half of them subsequently had an elevated level, > 20 mIU/mL, within the
      year. Between cycle days 2, 3 and 4, FSH (coefficient of variation [CV] = 14.8%,
      95% confidence interval (CI) = 11.4-18.3%) varied less than E2 (CV = 31.1%, 95%
      CI = 21.5-40.6%). CONCLUSION: A single day 3 FSH level < 20 mIU/mL is highly
      predictive of all subsequent values within a year and occurred only in women
      under 40. An FSH level drawn on cycle day 2 or 4 will probably be within 18% of
      the day 3 value, but the E2 level may vary by up to 40%.

PMID- 8576877
TI  - Identification and treatment of leukocytospermia in couples with unexplained
      infertility.
AB  - OBJECTIVE: To evaluate whether identifying men with leukocytospermia in couples
      with unexplained infertility and treating them with antibiotics improves
      pregnancy rates. STUDY DESIGN: A prospective, cohort study of men with and
      without leukocytospermia was identified on a smear of semen using Bryan-Leishman
      stain. Cumulative six-month pregnancy rates were determined for members of the
      leukocytospermic group who responded to treatment with resolution of their
      leukocytospermia on a semen smear, those who failed to respond to treatment,
      those not treated and those without leukocytospermia. RESULTS: Thirty-six of 53
      men with leukocytospermia responded to antibiotic treatment, and 19 women in
      these 36 couples (53%) became pregnant within the six-month follow-up period.
      Only 7 of 17 (6%) of those who failed to respond to treatment had their partner
      become pregnant (P < .001). Partners of men with leukocytospermia and no
      treatment had a 6% pregnancy rate, and the women in 13% (5/42) of couples without
      leukocytospermia became pregnant (P < .001). CONCLUSION: Leukocytospermia exists
      in a significant number of males with unexplained infertility and normal semen
      analyses. Identifying and successfully treating such men results in a significant
      improvement in pregnancy rates. These men may be a subgroup with male infertility
      that can be identified and treated.

PMID- 8576878
TI  - Spontaneous pregnancy in women awaiting oocyte donation.
AB  - OBJECTIVE: To evaluate the rate of spontaneous pregnancy in women awaiting oocyte
      donation. STUDY DESIGN: Two hundred women with histories of hypergonadotropic
      hypogonadism (follicle-stimulating hormone > 60 mIU/mL, estradiol < 20 pg/mL)
      were evaluated for oocyte donation. RESULTS: While awaiting gamete donation, five
      women (2.5% of patients monitored) spontaneously conceived. Their ages ranged
      from 32 to 42 years (mean, 37.0 +/- 5.0) (mean +/- SD). Conceptions occurred 5.0
      +/- 2.6 years (range, two to eight) from their original diagnosis, while they
      were using hormone replacement therapy. Four of the five pregnancies continued
      uneventfully, and one patient spontaneously aborted. Subsequently all women
      demonstrated elevated serum gonadotropins and amenorrhea. CONCLUSION: Patients
      with hypergonadotropic hypogonadism may spontaneously conceive while awaiting
      oocyte donation.

PMID- 8576879
TI  - Extended induction of ovulation by human menopausal gonadotropins and a
      gonadotropin-releasing hormone analog in high responders for in vitro
      fertilization and oocyte donation.
AB  - OBJECTIVE: To examine the efficacy of extending ovulation induction for the in
      vivo maturation of oocytes. STUDY DESIGN: Fifty-nine high responders underwent 72
      in vitro fertilization (IVF) cycles with a conventional protocol of human
      menopausal gonadotropin and a gonadotropin-releasing hormone analog. These
      patients donated oocytes to 81 recipients. The same 59 patients underwent 90
      subsequent cycles in which the duration of induction was extended by two to three
      days. The oocytes were also donated to 138 patients. RESULTS: With the extended
      protocol, significantly more oocytes were retrieved (29.1 vs. 20.6), and a
      greater proportion of them were mature. Fertilization rates were significantly
      higher for both donors (67.7% vs. 36.2%) and recipients (67.5% vs. 47.1%).
      Conception rates were also significantly higher for both donors (24.4% vs. 11.1%)
      and recipients (38.4% vs. 24.7%). CONCLUSION: Extending the duration of ovulation
      induction in high responders is associated with in vivo maturation of oocytes and
      improved success rates in IVF and ovum-donation programs.

PMID- 8576880
TI  - Subdermal levonorgestrel implants. Three years' experience in Cairo, Egypt.
AB  - OBJECTIVE: To assess the efficacy, safety and acceptability of the subdermal
      levonorgestrel implant (SLI), a new, long-acting, low-dose, progestin-only
      contraceptive method for women. STUDY DESIGN: A prospective, observational study
      conducted in the family planning clinic, Department of Obstetrics and Gynecology,
      Ain Shams University Hospital, Cairo, Egypt, as an advanced phase III clinical
      trial. RESULTS: This paper describes three years' experience with the SLI in 350
      women. The net three-year cumulative pregnancy rate was 0.98%. Menstrual
      disturbances, ranging from amenorrhea to menorrhagia, were the major side effects
      and were present in 25% of women during the third year. These disturbances
      resulted in 28 removals, 19 of which were because of amenorrhea. Medical
      complications, including headache, hypertension and non-insulin dependent
      diabetes; desire for pregnancy; and complications at the insertion site (such as
      infection, spontaneous expulsion of the capsules and arm pain) were the principal
      reasons for another 57 implant removals. So far, no gynecologic or breast lesions
      have developed, and weight changes were not noted. The continuation rate after
      three years was 65.5%. CONCLUSION: The efficacy, safety and acceptability of the
      implant suggest that it will provide an important addition to the contraceptive
      armamentarium.

PMID- 8576881
TI  - Duration and variability of normal pregnancy. Implications for clinical practice.
AB  - OBJECTIVE: To estimate the true biologic length and variability of normal
      pregnancy on the basis of early ultrasonography and to assess the implications
      for clinical practice. STUDY DESIGN: We reviewed the clinical case notes on 476
      women whose pregnancies were routinely dated by measurement of the biparietal
      diameter in the second trimester. After excluding abnormal cases, 355 pregnancies
      were available for analysis. The duration of pregnancy was studied in relation to
      maternal characteristics and also to induction of labor for postmaturity.
      RESULTS: The mean +/- SD for the normal duration of pregnancy were 279.7 and 7.4
      days. The length of pregnancy was weakly related to maternal height. Of the 41
      women whose labor was induced for postmaturity, only 7 were truly postmature when
      gestational age was determined by sonography. CONCLUSION: The current definitions
      of preterm and postterm may need to be revised to allow the increased precision
      achieved by ultrasound. Inclusion of menstrual data for the determination of
      gestational age may lead to incorrect clinical decisions.

PMID- 8576882
TI  - Streptococcus pneumoniae pelvic inflammatory disease. A case report.
AB  - BACKGROUND: Single-agent causes of pelvic inflammatory disease (PID) are
      uncommon. Streptococcus pneumoniae, as the suspected sole causative bacterium,
      has been reported since the 1800s. In the postantibiotic era, 46 cases have been
      reported, with a high mortality rate. CASE: We report a case of S pneumoniae as a
      single bacterial etiology of PID. This single bacterial species was documented by
      separate cervicovaginal, culdocentesis and laparoscopic cultures. CONCLUSION: It
      is unusual to identify an uncommon, single organism as the causative bacterial
      species in PID in an immunocompetent patient without evidence of a primary
      infectious pneumococcal source.

PMID- 8576883
TI  - Occult retrocervical endometriosis. A case report.
AB  - BACKGROUND: The retrocervical area of the pelvis is a particularly strategic
      location for dyspareunia-producing endometriotic lesions. Because this area is
      often hidden from view by the cervical bulge, it is necessary that close
      attention be paid to locating occult disease. CASE: A 35-year-old, white female
      underwent repeat laparoscopy for persistent dyspareunia. Occult retrocervical
      disease was found and exercised. CONCLUSION: Incomplete treatment may result if
      this area is not examined and biopsied.

PMID- 8576884
TI  - Spontaneous intrauterine remission of fetal ascites in one identical twin. Report
      of a case with ultrasound evaluation.
AB  - BACKGROUND: Fetal ascites is usually a precursor of, or one of the findings in,
      hydrops fetalis. The spontaneous intrauterine remission of fetal ascites,
      especially in twin pregnancy, is extremely low. CASE: A woman had sonographically
      documented fetal ascites in one identical twin. The workup for immunologic or
      nonimmunologic causes was negative except for the absence of end diastolic flow
      in the umbilical artery, demonstrated by Doppler ultrasonography in the affected
      fetus. Subsequent sonographic examinations demonstrated disappearance of the
      ascites as resistance of the umbilical artery progressively improved. CONCLUSION:
      In evaluating the hemodynamic changes in this condition, Doppler ultrasonography
      can elucidate the pathophysiology of fetal ascites formation in a monochorionic
      twin and also provide information for guiding management.

PMID- 8576885
TI  - Massive vulvar edema in ovarian hyperstimulation syndrome. A case report.
AB  - BACKGROUND: Bilateral vulvar edema associated with severe ovarian
      hyperstimulation syndrome is described for the first time. CASE: A 28-year-old
      woman underwent gonadotropin-releasing hormone analogue and gonadotropin
      treatment for in vitro fertilization and embryo transfer. On day 18 of the cycle,
      the patient reported mild abdominal discomfort that became severe during the
      following four days. One the 22nd day of the cycle, bilateral ovarian enlargement
      and ascites were present. The vulva showed massive edema and fissures. Ovarian
      hyperstimulation syndrome (OHSS) therapy consisted of human albumin, lactated
      Ringer's solution and heparin. The vulvar edema was treated with topical
      hydrocortisone ointment, ice packs and topical gentamycin twice a day. After one
      week of treatment, the vulva was normal. CONCLUSION: We think that the vulvar
      edema in this case was the result of decreased oncotic pressure and increased
      hydrostatic pressure, as occur during OHSS.

PMID- 8576886
TI  - Cerebellar hemangioblastoma complicating pregnancy. A case report.
AB  - BACKGROUND: Cerebellar hemangioblastomas are unusual benign neoplasms that may go
      undetected for years. When associated with pregnancy, however, these tumors may
      undergo rapid expression and promote progression of symptomatology. CASE: A 28
      year-old woman with ataxia and left-sided weakness was diagnosed with cerebellar
      hemangioblastoma in the second trimester of pregnancy following repeated hospital
      admissions for nausea and vomiting. Surgical removal was uneventful, and she
      delivered vaginally at term. CONCLUSION: Cerebellar hemangioblastomas, although
      rare, should be considered in the differential diagnosis of persistent nausea and
      vomiting when accompanied by an abnormal neurologic examination.

PMID- 8576887
TI  - Aggressive angiomyxoma of the pelvis and perineum. A case report.
AB  - BACKGROUND: Aggressive angiomyxoma of the female perineum and pelvis is a slowly
      growing neoplasm occurring almost exclusively in women of reproductive age. The
      tumor is characterized by its locally infiltrative behavior. The high recurrence
      rate has been attributed to incomplete surgical excision. CASE: A case of a huge,
      recurrent, aggressive angiomyxoma of the perineum and pelvis was treated.
      CONCLUSION: Correct preoperative diagnosis and assessment of simultaneous
      perineal and pelvic involvement indicate a combined abdominoperineal surgical
      approach to achieve wide, tumor-free margins.

PMID- 8576888
TI  - Diagnostic considerations in coexisting bladder and urethral leiomyomata. A case
      report.
AB  - BACKGROUND: Leiomyomata of the lower urinary tract in women are rare. Coexisting
      urethral and bladder leiomyomata have never been reported before. CASE: A 45-year
      old woman, gravida 6, para 5, abortus 1, presented with a one-year history of
      increasing frequency, nocturia and hesitancy of up to 10-15 minutes at times. An
      intravenous pyelogram showed an extrinsic mass at the bladder neck.
      Urethrocystoscopy revealed a regular bulge at the level of the bladder neck on
      the right side without involvement of the bladder mucosa. Ultrasound showed a 5 x
      4.7 x 4-cm mass of heterogeneous echogenicity, posterior to the bladder and
      anterior to the lower uterine area, with a normal-appearing uterus. The patient
      underwent surgery for vaginal excision of the tumor. Two separate masses were
      found at surgery. One small, firm, solid, 2-cm mass was found on the posterior
      proximal aspect of the urethra, and a larger, soft, 3 x 3-cm mass was found on
      the posterior lower aspect of the bladder. The masses clearly arose from the
      urethra and bladder, respectively. Rapid frozen section revealed smooth muscle
      cells consistent with leiomyomata. Both leiomyomata were entirely resected.
      CONCLUSION: Lower urinary tract leiomyomata should always be considered in the
      differential diagnosis of an anterior vaginal mass in premenopausal women.

PMID- 8576889
TI  - Primary adenocarcinoma of the endometrium associated with genital tuberculosis. A
      case report.
AB  - BACKGROUND: Adenocarcinoma of the endometrium is a common tumor of the female
      reproductive tract, and tuberculosis accounts for only about 1% of postmenopausal
      metrorrhagia. Tuberculosis of the fallopian tubes is the most frequent location;
      that of the cervix is the most uncommon. CASE: A case of primary adenocarcinoma
      of the endometrium was diagnosed after curettage in a 58-year-old, postmenopausal
      woman complaining of a bloody vaginal discharge. A laparotomy was performed, and
      histologic examination of the uterus disclosed an endometrial carcinoma, grade
      2/3, with extension to both tubes. The tumor was associated with an extensive
      granulomatous reaction, with numerous tubercles composed of epithelioid cells,
      multinucleate giant cells of Langhans and central necrosis type. These granulomas
      were seen close to the carcinoma in the endometrium and tubes and far from the
      neoplasm in sections of the cervix, myometrium and lymph nodes. CONCLUSION: The
      association of endometrial adenocarcinoma with genital tuberculosis is extremely
      rare. Moreover, similar granulomas may appear in the surrounding stroma of the
      tumor. For these reasons a diagnosis of genital tuberculosis associated with this
      neoplasm should be made with caution.

PMID- 8576890
TI  - Massive metastases from a lobular breast carcinoma from an unknown primary during
      pregnancy. A case report.
AB  - BACKGROUND: Carcinoma of the breast during pregnancy represents 2-5% of all
      breast cancers. The frequency and histopathologic spectrum of breast cancer are
      similar in pregnant and nonpregnant women. Infiltrating lobular carcinoma is one
      of the less understood types of breast cancer, and its metastatic pattern seems
      to be different from that of infiltrating ductal carcinoma. Breast neoplasms
      rarely present as cancer from an unknown primary site. CASE: A woman in the third
      trimester of pregnancy developed carcinoma massively metastatic to the bone
      marrow and liver from an unknown primary tumor. At 32 weeks' gestation a healthy
      male was delivered by cesarean section. The patient died 12 hours after delivery.
      The autopsy revealed an infiltrating lobular carcinoma, 1.5 cm, of the breast.
      CONCLUSION: Massive metastases from an occult lobular breast carcinoma in a
      pregnant woman are very rare. Diffuse metastatic spread, which often complicates
      or delays the diagnosis, is a characteristic pattern of infiltrating lobular
      carcinoma. Cancer from an unknown primary site during pregnancy is an exceptional
      finding. If a metastatic adenocarcinoma is diagnosed in a pregnant woman, a
      breast primary should be strongly suspected.

PMID- 8576891
TI  - Is cardiovascular screening in primary care worthwhile?
AB  - Recent studies have demonstrated little benefit from multifactorial screening for
      coronary heart disease risk factors in family practice. The evidence in favour of
      a high risk approach, however, particularly for cholesterol lowering in the 5% of
      the population with known coronary heart disease is now stronger than ever. More
      effort will also be needed to find the older patients with levels of hypertension
      that need treatment in accordance with present guidelines. Finally a more
      committed approach should be made to stopping smoking especially in the young.

PMID- 8576892
TI  - Poisoning with anti-hypertensive drugs: methyldopa and clonidine.
AB  - Methyldopa and clonidine are anti-hypertensive drugs which are used less commonly
      nowadays. Experience of toxicity and self-poisoning with these drugs remains
      limited. This review examines the cases reported in the literature of overdosage
      or poisoning with methyldopa and clonidine, and the presenting symptoms and
      management in such cases. With supportive therapy, the prognosis following
      toxicity with methyldopa and clonidine is good. Although an initial presentation
      with drowsiness or coma is common, careful attention should also be directed to
      any cardiovascular complications.

PMID- 8576893
TI  - Results of combination anti-hypertensive therapy after failure of each of the
      components. Department of Veterans Affairs Cooperative Study Group on Anti
      hypertensive Agents.
AB  - We randomised ambulatory men with diastolic blood pressure (BP) 95-109 mmHg
      without anti-hypertensive medication to single drug treatment with either
      hydrochlorothiazide 12.5-50 mg/day, atenolol 25-100 mg/day, captopril 25-100
      mg/day, clonidine 0.2-0.6 mg/day, diltiazem-SR 120-360 mg/day, prazosin 4-20
      mg/day or placebo in a double-blind prospective trial. The assigned drug was
      titrated to a goal BP of < 90 mm Hg. Patients not achieving goal BP were
      rerandomised to an alternative single active drug. Non-responders to the second
      drug received the first drug in combination with the second. Of the 102 non
      responders to both drugs who qualified for the combination, 59 (57.8%) responded.
      The combination pairs that included a diuretic achieved diastolic goal BP in 69%
      and < 140 mm Hg systolic in 77% compared with 51% and 46%, respectively, for
      those combinations without a diuretic (P = 0.067; P = 0.002). Six of the eight
      terminations due to adverse drug reactions were in combinations containing
      prazosin; three of these six were hypotensive reactions. We conclude that two
      single drugs of insufficient efficacy to control BP individually have a high
      probability of achieving goal BP when combined, especially if the combination
      contains a diuretic.

PMID- 8576894
TI  - Circadian rhythm of hypertensives in a Cameroon population: a pilot study.
AB  - The present study was designed to determine diurnal blood pressure (BP)
      variations in black hypertensive Africans in Cameroon. Also the study assessed
      sex differences associated with ambulatory BP measurements in this black
      population. A total of 69 adult Cameroonians aged 25-55 years, who attended a
      hypertensive clinic in Yaounde, Cameroon, were recruited on a voluntary basis.
      The mean ages of the males and females were 48.9 and 45.8 years, respectively.
      Ambulatory BP monitoring was recorded with Spacelabs ICR Model 5300 ambulatory BP
      monitoring systems. SBP, DBP and heart rate were measured every 30 min over a 24
      h period. There were no significant mean differences observed between males and
      females on 24 h, daytime or night-time BPs. Among the Cameroonians, 31.7% (20 of
      63) of the study population were 'non-dippers'. There were no sex difference for
      dippers compared with non-dippers. Significant nocturnal declines were noted for
      SBP, DBP, heart rate and mean arterial pressure. The results of the present study
      reveal that in this select Cameroonian population, there exists a nocturnal
      decline in BP.

PMID- 8576895
TI  - Blood pressure levels in school-age Japanese children: the Hisayama Study.
AB  - Blood pressure (BP) measurements were obtained on a total of 6325 children (3294
      boys and 3031 girls), aged 6-14 years, in Hisayama, Japan. All BPs were recorded
      in a sitting position by trained observers in a standardised manner. Standard
      mercury sphygmomanometers were used with commercially available cuffs, selected
      according to the arm circumference. Cuff size no. 3 (bladder width 9 cm, length
      23 cm) was the one most commonly selected in 84% of elementary schoolers aged 6
      11 years and in 35% of junior high schoolers aged 12-14 years. Mean systolic BPs
      (SBPs) increased from 89 mm Hg at age 6 years to 108 mm Hg at 14 years (a 21%
      increase) for boys and from 88 mm Hg to 102 mm Hg (a 16% increase) for girls.
      Diastolic BP (DBPs, Korotkoff phase IV, KIV) increased from ages 6 to 14 years to
      the same degree, from 58 mm Hg to 72 mm Hg (a 24% increase) for boys and from 58
      mm Hg to 70 mm Hg (a 21% increase) for girls. The increase in DBP (Korotkoff
      phase V, KV) was greater, from 48 mm Hg to 63 mm Hg (a 30% increase) for boys and
      from 48 mm Hg to 61 mm Hg (a 28% increase) for girls. The increase in mean SBP
      for adolescent boys was greater compared with that of girls; however, separation
      of age-specific values by sex was not observed for mean DBP (KIV) and DBP (KV).
      The cross-sectional relation between age and mean SBP levels was not linear.

PMID- 8576896
TI  - Is isolated systolic hypertension in the elderly more associated with left
      ventricular hypertrophy and significant carotid artery stenosis than mixed
      hypertension and isolated diastolic hypertension?
AB  - The association of electrocardiographic left ventricular hypertrophy (ECG-LVH)
      (212 subjects) and haemodynamically significant internal carotid artery stenosis
      (ICAS) (27 subjects) with isolated systolic hypertension (ISH), mixed
      hypertension (MHT) and isolated diastolic hypertension (IDH) was studied in
      untreated elderly patients. Subjects were those aged 67-86 years, drawn from a
      community screening programme for hypertension in Wales. The prevalence of ECG
      LVH with or without repolarisation abnormalities was higher in subjects with ISH
      (16.6%) than in subjects with mixed hypertension (11.6%, NS). Partial correlation
      of SBP, DBP, voltage of lead I and SV1+RV5 for each hypertensive subtype showed a
      consistent positive correlation of DBP with the voltage of lead I and SV1+RV5 in
      all the subtypes except with the voltage of lead I in IDH subjects. In MHT, the
      SBP was inversely related to both the voltage of R-wave in lead I and SV1+RV5 (P
      < 0.03). In IDH, the SBP was positively correlated with the voltage of R-wave in
      lead I and inversely with SV1+RV5. Atheromatous plaque was present in 40 of 54
      (74.1%) internal carotid arteries investigated. The homogeneous type of plaque
      was predominant in ISH (67%). Heterogenous type of plaque was predominant in the
      MHT group (50%) and IDH group (43%). The normotensive group did not show any
      predilection to any morphological type. Plaque was invariably present in the case
      of ISH, chi 2 = 12.29, 0.1 > P > 0.05. There was more smooth plaque surface in
      normotensives (79%) and more rough or pitted plaque surface in hypertensives (all
      types), chi 2 = 6.51, 0.1 > P > 0.05. All normotensives and IDH subjects had non
      haemodynamically significant stenosis. Haemodynamically significant stenosis was
      found in cases of ISH (25%) and MHT (7%); chi 2 = 7.66, 0.1 > P > 0.05. ECG-LVH
      and haemodynamically significant internal carotid artery stenosis were more
      commonly found in subjects with ISH than in subjects with MHT. Further studies
      with larger numbers of patient in each hypertensive subtype would be desirable to
      confirm these observations.

PMID- 8576897
TI  - Endothelin-1 and neuropeptide Y plasma concentrations in renal venous blood of
      hypertensive patients with unilateral renal artery stenosis.
AB  - The aim of the study was to investigate endothelin-1 (ET-1) and neuropeptide Y
      (NPY) plasma concentrations in renal venous blood of hypertensive patients with
      unilateral renal artery stenosis (URAS). The study was performed in 22 patients
      with URAS and 18 patients diagnosed as essentially hypertensive. In each subject
      renal arteriography and renal vein catheterisation was performed. Blood samples
      for ET-1, NPY and plasma renin activity (PRA) were withdrawn from renal veins and
      vena cava inferior, and for ET-1 and NPY from the aorta. Patients with URAS were
      divided in two subgroups according to the renal vein renin ratio. Both in nine
      patients with URAS and ratio > 1.5 and in 13 patients with URAS and ratio < 1.5,
      ET-1 and NPY plasma concentrations evaluated in renal venous blood of the
      ischaemic kidney were not different from those assessed in the contralateral
      side, in vena cava inferior and in the aorta. In essential hypertension, the mean
      ET-1 and NPY plasma concentrations of both renal veins were not different from
      the ET-1 and NPY plasma values assessed in renal vein of stenosed and
      contralateral side, vena cava and aorta of patients with URAS with and without
      activation of the renin system. Our study indicates that chronic ischaemia does
      not affect ET-1 and NPY plasma concentrations in renal venous blood of
      hypertensive URAS patients both with and without activation of the renin system.

PMID- 8576898
TI  - Factors influencing the awake-sleep difference in ambulatory blood pressure: main
      effects and sex differences.
AB  - The purpose of this study was to assess the biological and behavioural
      characteristics associated with the variation in the awake-sleep blood pressure
      (BP) difference in a large series of patients who had ambulatory BP monitoring.
      The 1186 subjects in the study (689 men and 497 women) each wore an ambulatory BP
      monitor over one 24 h period. All patients had been off antihypertensive
      medication for at least 3 weeks prior to the BP monitoring. The extent of the
      difference in awake-sleep BP was defined by the percentage change to sleep
      pressure from the average awake value. The results showed that when the average
      levels of office, awake and sleep pressures are compared across groups defined by
      this percentage change, there is no statistically significant association between
      the level of office pressure and the extent of the awake-sleep pressure
      difference. In accordance with this finding, the relation between ambulatory
      awake BP and the awake-sleep difference was relatively weak, although significant
      (P < 0.01). In striking contrast, the ambulatory sleep pressure was a very strong
      predictor of the awake-sleep difference (P < 0.0001), such that subjects with the
      lowest sleep pressures had the biggest diurnal change. In examining the factors
      associated with the awake-sleep change in pressure, the most important predictors
      were a low sleep pressure and alcohol intake, both of which were associated with
      bigger diurnal changes of both SBP and DBP in both men and women. A large pulse
      pressure while awake (that is, isolated systolic hypertension) was also
      associated with bigger diurnal changes in both sexes. The only other predictive
      factor which applied in both sexes was a low awake BP variability which was
      associated with a greater diurnal variation of DBP. Among men but not women,
      older age, smoking cigarettes, and being overweight were associated with bigger
      diurnal changes of both SBP and DBP, and a family history of hypertension was
      also associated with a bigger diurnal change of systolic pressure. Finally, among
      women but not men, being measured in winter months was associated with a greater
      awake-sleep difference in diastolic pressure. These results show that there is a
      general pattern of factors which predict awake-sleep changes in men and women,
      but there are also contributing behavioural factors which are sex specific. As
      awake-sleep changes of BP may be of prognostic significance, behavioural factors
      need to be considered when evaluating this change.

PMID- 8576900
TI  - Management of hypertension in general practice: agreements with and variations
      from the British Hypertension Society guidelines.
AB  - A random sample of 200 East Anglian general practitioners was surveyed to
      establish current trends in the management of hypertension, including measurement
      of blood pressure (BP), patient investigation, treatment and follow-up. A total
      of 125 (62.5%) completed questionnaires was returned. Responses were used to
      assess the range of self-reported management practice and the extent of
      conformity with the British Hypertension Society guidelines. Although there was a
      broad spectrum of reported practice, many respondents adhered closely to the
      guidelines in relation to BP measurement, use of non-pharmacological treatment,
      treatment goals, choice of drug and patient investigation. Not surprisingly, the
      greatest disparity between reported and recommended practice occurred in areas
      where guidelines have only recently become available: treatment of isolated
      systolic hypertension and of the elderly hypertensive. Here, the survey provides
      a useful baseline against which to monitor future changes in management.

PMID- 8576899
TI  - Increased thickness of the carotid artery in patients with essential hypertension
      and microalbuminuria.
AB  - In patients with essential hypertension, the presence of microalbuminuria carries
      an increased risk for cardiovascular morbidity and mortality. The mechanisms
      responsible for this association are not clear. Microalbuminuria could signal the
      presence of generalised atherosclerosis. To determine the extent of
      atherosclerosis, we measured by B-mode ultrasound imaging the thickness of the
      intima and media layers of the carotid artery in 30 hypertensive patients with
      microalbuminuria, 30 patients without microalbuminuria and 30 normotensive
      healthy subjects. In hypertensive patients with microalbuminuria, urinary albumin
      excretion (55 +/- 4.7 mg/24 h) was greater (P < 0.01) than in patients without
      microalbuminuria (12 +/- 0.9 mg/24 h) and in healthy subjects (7.1 +/- 0.52 mg/24
      h). In hypertensive patients with microalbuminuria, the thickness of the carotid
      artery (0.78 +/- 0.02 mm) was greater (P < 0.01) than in patients without
      microalbuminuria (0.69 +/- 0.01 mm) and in healthy subjects (0.64 +/- 0.02 mm).
      In hypertensive patients with microalbuminuria, the mean insulin area-under-the
      curve (59,703 +/- 4,874 pmol/L x 2 h) and glucose area-under-the curve (928 +/-
      40.0 mmol/L x 2 h) were significantly greater (P < 0.005) than in patients
      without microalbuminuria (38,774 +/- 4,104 pmol/L x 2 h and 803 +/- 34.7 mmol/L x
      2 h, respectively), and in normotensive healthy subjects (27,557 +/- 2563 pmol/L
      x 2 h and 837 +/- 31.2 mmol/L x 2 h, respectively). Serum levels of total
      cholesterol, triglycerides and lipoprotein(a) were higher in hypertensives with
      than in those without microalbuminuria. The thickness of the carotid artery was
      significantly correlated with microalbuminuria, blood pressure, cholesterol,
      serum triglycerides and insulin area-under-the curve. In conclusion, this study
      shows that hypertensive patients with microalbuminuria have an increased
      thickness of the carotid intima and media layers suggesting a greater degree of
      atherosclerosis. Measurements of urinary albumin excretion may be important in
      the evaluation of patients with essential hypertension.

PMID- 8576901
TI  - Takayasu's arteritis as a cause of renovascular hypertension in a non-Asian
      population.
AB  - Takayasu's disease (TD) is a chronic inflammatory arteritis which affects the
      aorta and its main branches and occasionally the pulmonary artery. Its cause is
      not known. Clinical manifestations are due to the intensity and location of
      arterial inflammation in the acute phase, as well as chronic arterial stenosis
      over time; 50% of patients have hypertension. Although TD appears to be more
      common in Asia, increasing numbers of patients of different races are observed in
      Western countries. The most important pathogenetic mechanism of hypertension
      seems to be through renal artery stenosis. We show here seven Caucasian
      hypertensive patients with TD and renovascular stenosis and arterial
      hypertension. One case was diagnosed in the acute phase of the disease, while in
      the others diagnosis was established in an advanced occlusive phase. Basic
      diagnosis was established by angiographic study, with biopsy confirmation in two
      cases. All patients had at least three of the six criteria listed as diagnostic
      of TD (by the American College of Reumatology). All patients had the following
      criteria: age of disease onset before 40 years (symptoms or findings related to
      TD), vascular bruits in different areas and all patients also had aortic and
      renal arterial stenosis with some lesions of the main aortic branches. Six of
      them had claudication of the extremities. We describe their clinical, analytical
      and angiographic features and also the therapeutic approach. We discuss the
      aetiopathogenic mechanisms of hypertension in this disease and suggest that TD is
      not an unusual cause of vasculorenal hypertension.

PMID- 8576902
TI  - Body mass index, blood pressure, diabetes and the risk of anti-hypertensive drug
      treatment: 12-year follow-up of middle-aged people in eastern Finland.
AB  - We analysed the association of body mass index (BMI) with blood pressure (BP) at
      baseline, whether BMI predicts the incidence of anti-hypertensive drug treatment
      during a 12-year follow-up and whether this risk is independent of the original
      BP level and, finally, how diabetes associates with the incidence of anti
      hypertensive drug treatment. The study population comprised 15,438 men and women
      in eastern Finland aged between 30 and 59 years who were not using anti
      hypertensive drug treatment during baseline surveys in 1972 and 1977. At baseline
      BP increased linearly by increasing BMI. The proportion of hypertensive subjects,
      defined as either DBP > or = 95 mm Hg or SBP > or = 160 mm Hg, was 18% among the
      leanest men, BMI < 20 kg/m2, but 61% among the most obese, BMI > or = 30 kg/m2.
      Among women these proportions were 11% and 54%, respectively. Among the
      normotensive subjects at baseline, the BMI associated risk ratio of the incidence
      of anti-hypertensive drug treatment, adjusted for age and study year, was 1.14
      (per kg/m2; P < 0.001) in men and 1.11 (P < 0.001) in women. After a further
      adjustment for DBP and SBP at baseline, risk ratios were 1.13 (P < 0.001) and
      1.07 (P < 0.001), respectively. Diabetes associated with the risk of anti
      hypertensive drug treatment independently from BMI, DBP and SBP. Because BMI
      correlates with BP cross-sectionally, and it also predicts the future increase in
      BP independently from the baseline BP, excess weight is undoubtedly one of the
      most important risk factors for hypertension. Weight control is the most natural
      primary intervention method in the inter-relation of obesity, hypertension and
      diabetes and in the prevention of subsequent cardiovascular diseases.

PMID- 8576903
TI  - Blood pressure responses to phenylephrine infusions in subjects with Cushing's
      syndrome.
AB  - The pathogenesis of the hypertension associated with Cushing's syndrome is not
      completely understood. Sensitivity to pressor agents may play a role. We have
      investigated this possibility by measuring blood pressure (BP) during
      incrementally increasing infusions of the alpha-adrenergic agonist phenylephrine.
      Ten subjects (8 women: 2 men), aged 40 +/- 5 years (mean +/- s.e.m.) with
      Cushing's syndrome were studied. All had raised BP but none had received any anti
      hypertensive treatment for at least 16 days before study. Ten age- (40 +/- 5
      years) and sex-matched control subjects were also studied. At 13.30, 30 min after
      a light meal, subjects had an intravenous cannula inserted, ECG leads and a
      sphygomanometer cuff attached, and then rested supine in a quiet room for 30 min.
      Phenylephrine was then infused incrementally at intervals of 5 min. The doses
      used were 0.3, 0.6, 0.9, 1.35 and 2 micrograms/kg/min. Basal mean blood pressure
      (MAP) was 108 +/- 2 mm Hg (mean +/- s.e.m.) in patients and 74 +/- 3 mm Hg in
      controls (P < 0.05) and pulse rate was 75 +/- 5 and 68 +/- 3 beats/min (NS),
      respectively). MAP increased and pulse rate decreased linearly with time. The
      rate of rise of MAP was 1.7 +/- 0.4 mm Hg/min in subjects and 1.1 +/- 0.2 mm
      Hg/min in controls (NS). The rate of decrease of pulse was significantly more
      rapid in Cushing's subjects than in controls (1.4 +/- 0.2; 0.6 +/- 0.1
      beats/min2; P < 0.05). The lack of any increased BP response to alpha-adrenergic
      stimulation suggests that altered sensitivity is not a major cause of the
      increased BP seen in patients with Cushing's syndrome.

PMID- 8576904
TI  - Nonpeptide angiotensin II receptor antagonists: the next generation in
      antihypertensive therapy.

PMID- 8576905
TI  - alpha-Phosphonosulfonic acids: potent and selective inhibitors of squalene
      synthase.

PMID- 8576906
TI  - Orally active squalene synthase inhibitors: bis((acyloxy)alkyl) prodrugs of the
      alpha-phosphonosulfonic acid moiety.

PMID- 8576907
TI  - The structure-activity relationship between peroxisome proliferator-activated
      receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones.

PMID- 8576908
TI  - 2-Iminopiperidine and other 2-iminoazaheterocycles as potent inhibitors of human
      nitric oxide synthase isoforms.
AB  - A series of 2-iminoazaheterocycles have been prepared and shown to be potent
      inhibitors of human nitric oxide synthase (NOS) isoforms. This series includes
      cyclic amidines ranging from five- to nine-membered rings, of which 2
      iminopiperidine and 2-iminohomopiperidine were the most potent inhibitors, with
      IC50 values of 1.0 and 2.0 microM, respectively, for human inducible nitric oxide
      synthase. This series of cyclic inhibitors was further expanded to include
      analogs with heteroatoms in the 3-position of the six-membered ring. This
      modification was tolerated for sulfur and oxygen, but nitrogen reduced the
      inhibitory potency. The oral administration of 2-iminopiperidine in
      lipopolysaccharide (LPS)-treated rats inhibited the LPS-induced increase in
      plasma nitrite/nitrate levels in a dose-dependent manner, demonstrating its
      ability to inhibit inducible NOS activity in vivo. These cyclic amidines
      represent a new class of potent NOS inhibitors and the foundation for potential
      therapeutic agents.

PMID- 8576909
TI  - Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone
      antibacterial agents for the potential treatment of multidrug-resistant gram
      positive bacterial infections.
AB  - Bacterial resistance development has become a very serious clinical problem for
      many classes of antibiotics. The 3-aryl-2-oxazolidinones are a relatively new
      class of synthetic antibacterial agents, having a new mechanism of action which
      involves very early inhibition of bacterial protein synthesis. We have prepared
      two potent, synthetic oxazolidinones, U-100592 and U-100766, which are currently
      in clinical development for the treatment of serious multidrug-resistant Gram
      positive bacterial infections caused by strains of staphylococci, streptococci,
      and enterococci. The in vitro and in vivo (po and iv) activities of U-100592 and
      U-100766 against representative strains are similar to those of vancomycin. U
      100592 and U-100766 demonstrate potent in vitro activity against Mycobacterium
      tuberculosis. A novel and practical asymmetric synthesis of (5S)
      (acetamidomethyl)-2-oxazolidinones has been developed and is employed for the
      synthesis of U-100592 and U-100766. This involves the reaction of N
      lithioarylcarbamates with (R)-glycidyl butyrate, resulting in excellent yields
      and high enantiomeric purity of the intermediate (R)-5-(hydroxymethyl)-2
      oxazolidinones.

PMID- 8576910
TI  - Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial
      activity.
AB  - During the course of our investigations in the oxazolidinone antibacterial agent
      area, we have identified a subclass with especially potent in vitro activity
      against mycobacteria. The salient structural feature of these oxazolidinone
      analogues, 6 (U-100480), 7 (U-101603), and 8 (U-101244), is their appended
      thiomorpholine moiety. The rational design, synthesis, and evaluation of the in
      vitro antimycobacterial activity of these analogues is described. Potent activity
      against a screening strain of Mycobacterium tuberculosis was demonstrated by 6
      and 7 (minimum inhibitory concentrations or MIC's < or = 0.125 micrograms/mL).
      Oxazolidinones 6 and 8 exhibit MIC90 values of 0.50 micrograms/mL or less against
      a panel of organisms consisting of five drug-sensitive and five multidrug
      resistant strains of M. tuberculosis, with 6 being the most active congener.
      Potent in vitro activity against other mycobacterial species was also
      demonstrated by 6. For example, 6 exhibited excellent in vitro activity against
      multiple clinical isolates of Mycobacterium avium complex (MIC's = 0.5-4
      micrograms/mL). Orally administered 6 displays in vivo efficacy against M.
      tuberculosis and M. avium similar to that of clinical comparators isoniazid and
      azithromycin, respectively. Consideration of these factors, along with a
      favorable pharmaco-kinetic and chronic toxicity profile in rats, suggests that 6
      (U-100480) is a promising antimycobacterial agent.

PMID- 8576911
TI  - Slow-binding inhibition of gamma-aminobutyric acid aminotransferase by hydrazine
      analogues.
AB  - (3-Hydroxybenzyl)hydrazine and methylhydrazine have been found to be potent slow
      binding inhibitors of the pyridoxal 5-phosphate (PLP)-dependent enzyme gamma
      aminobutyric acid aminotransferase (GABA-AT). Both compounds follow mechanism A
      (Morrison, J.F.; Walsh, C. T. Adv. Enzymol. 1988, 61, 201-301) which does not
      involve formation of a rapidly reversible enzyme-inhibitor complex before the
      formation of the final tight complex. The rate constant for formation of the
      enzyme-inhibitor complex determined from the slow-binding kinetics was 2.08 x
      10(3) and 1.98 x 10(4) M-1 min-1 for methylhydrazine and (3
      hydroxybenzyl)hydrazine, respectively. The rate constant for dissociation of the
      enzyme--inhibitor complex determined for the slow-binding kinetics was 4.6 x 10(
      3) and 5 x 10(-3) min-1, respectively. The inhibition constants calculated from
      the slow-binding inhibition kinetics are 2.2 microM for methylhydrazine and 0.3
      microM for (3-hydroxybenzyl)hydrazine. Reactivation of the inhibited enzyme was
      not first order, perhaps due to a side reaction of the hydrazine, but was
      consistent with the results obtained from the slow-binding kinetics. Inhibition
      constants were calculated from the level of enzyme activity at equilibrium
      inhibition. These constants are 2.8 and 0.46 microM for methylhydrazine and (3
      hydroxybenzyl)hydrazine, respectively, in good agreement with those calculated
      from the slow-binding inhibition kinetics. 3-Hydrazinopropionate also behaved as
      a slow-binding inhibitor. However, the dependence of its kinetics on the
      concentration of inhibitor could not be described by the slow-binding or slow,
      tight-binding inhibition models. These kinetics could not be described by the
      tight-binding character of the inhibition because the addition of the competitive
      inhibitor propionic acid at 100 times its Ki did not affect the shape of the
      curve for inhibitor concentration dependence. The slow-binding inhibition
      appeared to require 2-4 molecules of 3-hydrazinopropionate/enzyme. The
      reactivation of enzyme inhibited by 3-hydrazinopropionate was first order with a
      rate constant of 6.9 x 10(-3) min-1. Its equilibrium inhibition constant was
      calculated to be < 20 nM. However, the inhibition constant calculated was
      dependent on the concentration of inhibitor because of the unusual character
      discussed above and may be much lower. Only 1 PLP/enzyme dimer reacted with
      methylhydrazine or (3-hydroxybenzyl)hydrazine, as indicated by Scatchard plots,
      or with 3-hydrazinopropionate, as shown by a spectrophotometric titration. Slow
      binding inhibition does not appear to be the result of a significant enzyme
      conformational change because there is no change in the tryptophan fluorescence
      of GABA-AT upon binding either methylhydrazine or 3-hydrazinopropionate.
      Implications for the design of hydrazine inhibitors of GABA-AT are discussed.

PMID- 8576912
TI  - Quinazoline antifolates thymidylate synthase inhibitors: lipophilic analogues
      with modification to the C2-methyl substituent.
AB  - Modification of the potent thymidylate synthase (TS) inhibitor 1-[[N-[4-[N-[(3,4
      dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl]-N- prop-2
      ynylamino]benzoyl]amino]methyl]-3-nitrobenzene (4a) has led to the synthesis of
      quinazolinone antifolates bearing functionalized alkyl substituents at C2. A
      general synthetic route was developed which involved coupling the appropriate 1
      [[N-[4-(alkylamino)benzoyl)amino]methyl]-3-nitrobenzene 20-22 with a 6
      (bromomethyl)-2-(acetoxymethyl)-3,4-dihydro-4-oxoquinazoline 9 or 10. Replacement
      of the 2-acetoxy group by a chlorine atom followed by the displacement of the
      halogen of 25a-c by various nucleophiles led to compounds 26-40. Good TS (IC50 <
      1 microM) and growth inhibition (IC50 0.1-1 microM) were found with most of these
      new antifolates. TS inhibitors in this series do not apparently require the
      reduced folate carrier (RFC) for cell entry (they most likely penetrate the cell
      membrane by passive diffusion) and are not polyglutamated. N, O, S, Cl, and CN as
      well as large amino and mercapto substituents were tolerated by the enzyme. The
      simultaneous incorporation of 7-methyl and 2'-F substituents gave a series of
      highly potent agents inhibiting cell growth at concentrations < 1 microM (24,
      27bc; 30-32b, 35b). The incorporation of suitable C2 substituents has overcome
      the decrease in aqueous solubility observed with lipophilic quinazoline
      antifolates. This is best illustrated by compound 31a, where up to a 54-fold
      increase in solubility has been achieved by the incorporation of an N
      methylpiperazine nucleus into the C2-methyl group of 4a.

PMID- 8576913
TI  - An approach to rapid estimation of relative binding affinities of enzyme
      inhibitors: application to peptidomimetic inhibitors of the human
      immunodeficiency virus type 1 protease.
AB  - This report describes a method for rapid assessment of the binding affinities of
      a series of analogous ligands to an enzyme. This approach is based on two
      variables (scores), representing (i) the enthalpy of binding and (ii) the
      strength of hydrophobic interaction. The method is then used to evaluate the
      binding of 11 different peptidomimetic inhibitors to the HIV-1 protease. Three
      dimensional structures of these enzyme-inhibitor complexes are modeled based on
      the crystal structures of HIV-1 protease complexes with the known inhibitors.
      These structures are minimized using the AMBER force field, and the scores of
      binding enthalpy for each of the ligands are calculated. A second score to
      represent the hydrophobic interaction between a pair of atoms uses an exponential
      function of distance between the atoms and the product of their atomic
      hydrophobicity constants. This exponential function is used to assess the
      hydrophobic interaction energy between an enzyme and its inhibitor and also to
      compute and display a 'molecular hydrophobicity map' as a 3D visualization tool.
      These methods are then applied to obtain trends in relative binding affinities of
      pairs of analogous inhibitors. Calculated scores agree well with corresponding
      results from thermodynamic cycle perturbation (TCP) simulations as well as
      experimental binding data. Since the proposed calculations are computationally
      cheaper and faster than TCP calculations, it is suggested that these scores can
      form the basis for rapid, preliminary theoretical screening of proposed
      derivatives of an inhibitor prior to TCP analysis, synthesis, and testing.

PMID- 8576914
TI  - Water soluble inhibitors of topoisomerase I: quaternary salt derivatives of
      camptothecin.
AB  - Eleven water soluble 7-substituted quaternary ammonium salt derivatives of 10,11
      (methylenedioxy)- and 10,11-(ethylenedioxy)-(20S)-camptothecin were synthesized
      via the Friedlander reaction followed by nucleophilic displacement with an
      aromatic amine. All of these compounds were more potent than camptothecin in the
      in vitro cleavable complex assay. These inherently charged camptothecin
      derivatives were cytotoxic against three different human tumor cell lines (SKOV3,
      an ovarian adenocarcinoma; SKVLB a multidrug resistant ovarian adenocarcinoma;
      and HT-29, a colon carcinoma). A selected group of five compounds was evaluated
      in the nude mouse HT-29 xenograft model. Two of these quaternary salts (17 and
      18) were more efficacious than Topotecan in delaying tumor growth. In an extended
      in vivo model, 18 demonstrated tumor regression.

PMID- 8576915
TI  - In vivo activity and hydrophobicity of cytostatic aziridinyl quinones.
AB  - For a series of 3,6-disubstituted bisaziridinylbenzoquinones the in vivo and in
      vitro activities against murine tumors, as well as the in vivo toxicity, are
      analyzed. Properties describing biochemical and physicochemical reactions are
      also incorporated in the analyses. The important 1-octanol/water partition
      coefficients were determined, using a fast variation of the shake flask method.
      New pi'-values were calculated for the substituents in this series. These quinone
      pi'-values deviate strongly from the standard pi-values, especially for hydrogen
      bonding substituents. To discriminate between the toxic and therapeutic activity
      of the compounds, principal components and partial least squares analyses were
      applied. Evidence is presented for selective antitumor action of the investigated
      compounds. The L1210 clonogenic assay only seems to relate to the general
      cytotoxicity and has no predictive value for in vivo activity for these
      compounds. The activity is correlated to the hydrophobicity of the quinones. The
      toxicity correlates with the ease of reduction, contrary to the hypothesis of
      bioreductive activation as a mechanism for selectivity.

PMID- 8576916
TI  - Structure-activity relationships of the quinolone antibacterials against
      mycobacteria: effect of structural changes at N-1 and C-7.
AB  - The re-emergence of tuberculosis infections which are resistant to conventional
      drug therapy has demonstrated the need for alternative chemotherapy against
      Mycobacterium tuberculosis. As part of a study to optimize the quinolone
      antibacterials against M. tuberculosis, we have prepared a series of N-1- and C-7
      substituted quinolones to examine specific structure-activity relationships
      between modifications of the quinolone at these two positions and activity
      against mycobacteria. The compounds, synthesized by literature procedures, were
      evaluated for activity against Mycobacterium fortuitum and Mycobacterium
      smegmatis as well as Gram-negative and Gram-positive bacteria. The activity of
      the compounds against M. fortuitum was used as a barometer of M. tuberculosis
      activity. The results demonstrate that (i) the activity against mycobacteria was
      related more to antibacterial activity than to changes in the lipophilicity of
      the compounds, (ii) the antimycobacterial activity imparted by the N-1
      substituent was in the order tert-butyl > or = cyclopropyl > 2,4-difluorophenyl >
      ethyl approximately cyclobutyl > isopropyl, and (iii) substitution with either
      piperazine or pyrrolidine heterocycles at C-7 afforded similar activity against
      mycobacteria.

PMID- 8576917
TI  - 3-Aryl-1,2-diacetamidopropane derivatives as novel and potent NK-1 receptor
      antagonists.
AB  - Early structure-activity studies on racemic tryptophan ester and amide NK-1
      antagonists 5-7 led to the discovery that the potency of the series could be
      markedly increased by moving the carbonyl function in these molecules to an off
      chain position as in the 3-aryl-1,2-diacetamidopropane 9. Further medicinal
      chemistry incorporating this change resulted in the discovery of a novel series
      of highly potent aryl amino acid derived NK-1 antagonists of the R stereoisomeric
      series (IC50's = 100 pM to > 5 microM). Compounds in this series were shown to be
      competitive antagonists using an in vitro NK-1 smooth muscle assay, and this data
      correlated well with observed human NK-1 binding affinities. Two of these agents,
      (R)-25 and (R)-32, blocked intrathecal NK-1 agonist-driven [Ac
      [Arg6,Sar9,Met(O2)11]- substance P 6-11 (Ac-Sar9)] nociceptive behavior in mice.
      Both compounds potently blocked the neurogenic dural inflammation following
      trigeminal ganglion stimulation in the guinea pig after intravenous
      administration. Further, upon oral administration in this model, (R)-32 was
      observed to be very potent (ID50 = 91 ng/kg) and have a long duration of action
      (> 8 h at 1 micrograms/kg). Compound (R)-32, designated LY303870, is currently
      under clinical development as an NK-1 antagonist with a long duration of action.

PMID- 8576918
TI  - Structure-activity relationship studies of novel 4-[2-[bis(4
      fluorophenyl)methoxy]ethyl]-1-(3-phenylpropyl)piperidine analogs: synthesis and
      biological evaluation at the dopamine and serotonin transporter sites.
AB  - Several analogs of the potent dopamine (DA) transporter ligand 4-[2-[bis(4
      fluorophenyl)-methoxy]ethyl]-1-(3-phenylpropyl)piperidine, 1b, were made and
      biologically evaluated for their binding at the DA and serotonin (5HT)
      transporters in rat striatal membranes. Different alkyl chain lengths and
      substitutions were introduced in these molecules to generate an optimum activity
      and selectivity for the DA transporter. In general, unsubstituted and fluoro
      substituted compounds were the most active and selective for the DA transporter.
      The compound 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine, 9a, showed high
      potency and was the most selective for the DA transporter (5HT/DA = 49) in this
      series of compounds. Some of these novel analogs were found to be more selective
      in binding at the DA transporter than the original GBR 12909 molecule, 1-[2
      ]bis(4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperidine.

PMID- 8576919
TI  - Structure-activity relationships of a new family of steroidal aromatase
      inhibitors. 1. Synthesis and evaluation of a series of analogs related to 19
      [(methylthio)methyl]androstenedione (RU54115).
AB  - During the course of a study aimed at the search for new potent aromatase
      inhibitors, several new androstenedione analogs were synthesized and evaluated.
      This study led to the discovery of 19-[(methylthio)methyl]androsta-4,9(11)-diene
      3,17-dione (7; RU54115) already described by our laboratory. The object of the
      present series of papers is to disclose the result of the structure-activity
      relationship studies that gave rise to this compound. This first part deals
      mainly with the substitution in the 19-position of the steroid nucleus. Several
      parameters were varied, the length of the chain and its rigidity and branching,
      as well as the nature of the heteroatom itself and its substitution. The
      interaction of these new compounds with human placental aromatase in competition
      with the substrate androstenedione was studied by difference visible
      spectroscopy. The in vivo aromatase-inhibiting activities were evaluated by
      measuring the estradiol lowering after oral administration of the compounds to
      PMSG-primed female rats.

PMID- 8576920
TI  - Design and synthesis of 1-aminocycloalkane-1-carboxylic acid-substituted
      deltorphin analogues: unique delta and mu opioid activity in modified peptides.
AB  - Deltorphin analogues were substituted by a series of achiral C alpha,alpha
      dialkyl cyclic alpha-amino acids (1-aminocycloalkane-1-carboxylic acids, Ac chi
      c, where chi = a hexane, pentane, or propane cycloalkane ring) in position 2, 3,
      4, or 2 and 3 in deltorphin C, and in position 2 in [Ac6c2,-des-Phe3]deltorphin C
      hexapeptide. Receptor assays indicated that even though Ac6c2 and Ac6c3 exhibited
      a diminished Ki delta by ca. 20-fold (2.5-3.3 nM) relative to deltorphin C (Ki
      delta = 0.15 nM), selectivity was marginally elevated (Ki mu/Ki delta = 1250) or
      enhanced by about 70%, and both peptides fitted stringent iterative calculations
      for a two-site binding model (eta = 0.625 and 0.766, respectively, P < 0.0001).
      The disubstituted [Ac6c2,3]- or [Ac6c2,des-Phe3]deltorphin analogues yielded
      peptides with decreased Ki delta, such that the latter peptide was essentially
      inactive. The presence of Ac5c or Ac3c in place of Phe3 further diminished Ki
      delta (15.4 to 19.0 nM), yet delta selectivity only fell about one-half (Ki mu/Ki
      delta = 440 and 535, respectively), and only the former peptide fitted a two-site
      binding model (eta = 0.799). The replacement of Asp4 by Ac6c, Ac5c, or Ac3c
      produced essentially nonselective analogues through the acquisition of high mu
      affinities (2.5, 0.58 and 0.27 nM, respectively) while maintaining high delta
      affinities (Ki delta = 0.045-0.054 nM) which were about 3-fold greater than that
      of deltorphin C. Using pharmacological assays in vitro (mouse vas deferens and
      guinea pig ileum), position 3-substituted analogues all indicated substantial
      losses in bioactivity, whereas substitution by 1-aminocycloalkanes at the fourth
      position retained high delta activity. In fact, the bioactivity of
      [Ac3c4]deltorphin C indicated a peptide with relatively weak delta selectivity,
      which was comparable to the observations with the receptor binding data. In
      summary, the data confirmed that (i) delta selectivity occurs in the absence of D
      chirality at position 2, (ii) the aromaticity of Phe3 is replaceable by an
      achiral residue with a hydrophobic ring-saturated side chain, and (iii) the
      acquisition of dual high-affinity analogues occurs through the elimination of the
      anionic function at position 4 and replacement by an amino acid with a
      hydrophobic side chain.

PMID- 8576921
TI  - Interactions of flavonoids and other phytochemicals with adenosine receptors.
AB  - Flavone derivatives and other phytochemicals were found to bind to three subtypes
      of adenosine receptors in the micromolar range. Affinity was determined in
      radioligand binding assays at rat brain A1 and A2A receptors using [3H]-N6-PIA
      ([3H]-(R)-N6-phenylisopropyladenosine) and [3H]CGS21680 ([3H]-2-[[4-(2
      carboxyethyl)phenyl]ethylamino]-5'- (N-ethylcarbamoyl)adenosine), respectively.
      Affinity was determined at cloned human and rat brain A3 receptors using [125I]
      AB-MECA [N6-(4-amino-3-iodobenzyl)adenosine-5'-(N-methyluronamide)]. A structure
      activity analysis indicated that the hydroxyl groups of naturally occurring
      flavones are not essential for affinity at adenosine receptors. Galangin, 14,
      displayed Ki values of 1 microM at both rat A1 and A2A receptors and 3 microM at
      human A3 receptors. Methylation but not acetylation of the hydroxyl groups of
      galangin enhanced A3 affinity. Pentamethylmorin, 20, appeared to bind with 14-17
      fold selectivity for human A3 receptors vs rat A1 and A2A receptors, with a Ki
      value of 2.65 microM. Two flavone derivatives (14 and 15) showed 14-fold greater
      affinity at human vs rat A3 receptors. Reduction of the 2,3-olefinic bond, as in
      (+/-)-dihydroquercetin, or glycosidation, as in robinin, greatly diminished
      affinity. An isoflavone, genistein, also bound only very weakly at A3 receptors.
      alpha-Naphthoflavone had greater receptor affinity (0.79 microM at A1 receptors)
      than the beta-isomer. Other natural products of plant origin, including
      oxogalanthine lactam, hematoxylin, and arborinine were found to bind to A1
      adenosine receptors with Ki values of 3-13 microM. These findings indicate that
      the flavones, flavonols, flavanones, and other phytochemicals may provide leads
      for the development of novel adenosine antagonists. The unexpected finding of
      considerable affinity of flavones at both rat and human A3 receptors may explain
      some of the previously observed biological effects of these compounds.

PMID- 8576922
TI  - Synthesis and anti-herpes virus activity of 2'-deoxy-4'-thiopyrimidine
      nucleosides.
AB  - A series of 5-substituted 2'-deoxy-4'-thiopyrimidine nucleosides was synthesized
      and evaluated as potential antiviral agents. A number of analogues such as 2'
      deoxy-5-propyl-4'-thiouridine (3ii), 2'-deoxy-5-isopropyl-4'-thiouridine (3iii),
      5-cyclopropyl-2'-deoxy-4'-thiouridine (3iv), 2'-deoxy-4'-thio-5-vinyluridine
      (3viii), and 5-(2-chloroethyl)-2'-deoxy-4'-thiouridine (3xx) were found to be
      highly active against herpes simplex virus type-1 (HSV-1) and varicella zoster
      virus (VZV) in vitro with no significant cytotoxicity. The compound with the
      broadest spectrum of activity was 2'-deoxy-5-ethyl-4'-thiouridine (3i) which
      showed significant activity against HSV-1, HSV-2, and VZV.

PMID- 8576923
TI  - Antitumor 2-(aminocarbonyl)-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-
      hydrazines.
AB  - Several 2-(aminocarbonyl)-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydr azi nes
      were synthesized and primarily evaluated for antitumor activity against the
      murine L1210 leukemia. All of the compounds tested were capable of producing
      "cures" of mice bearing this tumor. One of the most active agents of this class,
      1,2-bis(methylsulfonyl)-1-(2-chloroethyl)- 2(-)[[2-chloroethyl)
      amino]carbonyl]hydrazine, was further evaluated against a spectrum of
      transplanted murine and human solid tumors. Pronounced activity was found against
      all of the tumors including the murine B16F10 melanoma, M109 lung carcinoma,
      M5076 reticulum cell sarcoma, and the human LX-1 lung carcinoma. The activities
      observed compared favorably with those of the established antitumor drugs,
      cyclophosphamide, mitomycin C, and the nitrosoureas, evaluated concomitantly.

PMID- 8576924
TI  - Novel N6-(substituted-phenylcarbamoyl)adenosine-5'-uronamides as potent agonists
      for A3 adenosine receptors.
AB  - A series of adenosine-5'-uronamide derivatives bearing N6-phenylurea groups have
      been synthesized and tested for their affinity at A1 and A2A adenosine receptors
      in rat brain membranes and at cloned rat A3 receptors from stably transfected CHO
      cells. Some N6-arylcarbamoyl derivatives, N6-((2-chlorophenyl)carbamoyl)-, N6-((3
      chlorophenyl)carbamoyl)-, and N6-((4-methoxyphenyl)carbamoyl)adenosine-5'
      ethyluronamide (4l-n), were found to have affinity at A3 receptors in the low
      nanomolar range (Ki values < 10 nM). In CHO cells stably transfected with the rat
      A3 receptor, compound 4n was found to be a full agonist in inhibiting adenylate
      cyclase activity. The present study represents the first example of N6-acyl
      substituted adenosine analogs having high affinity at adenosine receptors and, in
      particular, at the A3 receptor subtype.

PMID- 8576925
TI  - Applicability of small endomyocardial biopsies for evaluation of high energy
      phosphates and glycogen in the heart.
AB  - To evaluate variability of biochemical determination of energy stores in
      endomyocardial biopsies, we compared myocardial contents of high energy
      phosphates and glycogen in endomyocardial and transmural myocardial biopsies from
      12 75-kg pigs before, during, and after cardioplegia. Before cardioplegia,
      comparable amounts of adenine nucleotides and glycogen were found in left and
      right ventricular endomyocardial and left ventricular transmural biopsies.
      Phosphocreatine levels were lower in endomyocardial than in transmural biopsies.
      Significant correlations were observed between endomyocardial and transmural
      adenine nucleotide and glycogen contents but not phosphocreatine content. During
      cardioplegia, myocardial ATP and phosphocreatine contents increased and glycogen
      concentration tended to decrease. During reperfusion, ATP and glycogen levels
      decreased, whereas phosphocreatine levels increased remarkably. Transmural
      changes in left ventricular adenine nucleotide and glycogen levels were reflected
      in endomyocardial biopsies but those in phosphocreatine were not. By increasing
      the number of endomyocardial biopsies from one to three, within-subject variance
      was reduced from 33-47% to 14-23% of total variance whereas four or more biopsies
      only added minor further reduction in variability. In conclusion, endomyocardial
      biopsies yield representative estimates of the average myocardial content of
      adenine nucleotides and glycogen but not of phosphocreatine in the normal heart.
      Endomyocardial biopsies offer a sensitive estimate of the changes in myocardial
      adenine nucleotides and glycogen induced by cardioplegia and reperfusion.
      However, metabolite content in endomyocardial biopsies shows a high variability.
      Three or more endomyocardial biopsies are necessary to reduce variability to
      acceptable levels.

PMID- 8576926
TI  - Interleukin 1 alpha-induced expression of manganous superoxide dismutase reduces
      myocardial reperfusion injury in the rat.
AB  - We investigated the effects of pretreatment with interleukin (IL)-1 alpha on the
      expression of manganous (Mn) superoxide dismutase (SOD) mRNA and reperfusion
      induced arrhythmias and the size of myocardial infarct in rats. Male Wistar rats
      received 10 mg intraperitoneal injections of human recombinant IL-1 alpha. Their
      hearts were thereafter isolated at 6, 12, 24, 36 h. A Northern analysis showed
      that Mn-SOD mRNA was mainly expressed in the heart and slightly in kidney, but
      not in any other organs. The expression of Mn-SOD mRNA peaked at 6 h after the
      injection of IL-1 alpha. The Mn-SOD protein content was most increased 12 h after
      injection. In the isolated heart model, the rats were pretreated with IL-1 alpha
      24 h earlier and their hearts were perfused by the Langendorff method. After 20
      min of ischemia which was induced by a ligation of a coronary artery, reperfusion
      induced arrhythmias were observed. There were no significant differences in the
      incidence of ventricular arrhythmias between the IL-1 alpha pretreated and the
      untreated hearts. IL-1 alpha pretreatment significantly reduced the mean duration
      of the ventricular arrhythmias and also delayed the onset of arrhythmias. The
      effect of IL-1 alpha pretreatment was also investigated in a 30-min model of
      ischemia followed by a 3-min reperfusion in anesthetized rats. The infarct size
      expressed as a percentage of the area at risk was significantly reduced in the IL
      1 alpha pretreated hearts compared with the untreated hearts. The left
      ventricular systolic pressure increased significantly in rat hearts pretreated
      with IL-1 alpha. Our results therefore showed that the pretreatment with IL-1
      alpha induced the overexpression of Mn-SOD mRNA in the rat hearts and also
      suggested that pretreatment with IL-1 alpha 24 h before ischemia reduced the risk
      of ischemia-reperfusion injury.

PMID- 8576927
TI  - Decreased inotropic response to beta-adrenergic stimulation and normal
      sarcoplasmic reticulum calcium stores in the spontaneously hypertensive rat
      heart.
AB  - Cardiac hypertrophy in the spontaneously hypertensive rat has been shown to be
      accompanied by a diminished inotropic response to beta-adrenergic stimulation.
      This diminished response has been attributed to abnormalities in various
      components of the beta-adrenergic signaling system. There is also evidence that
      regulation of intracellular Ca2+ cycling may be altered in the hypertrophied
      heart of the spontaneously hypertensive rat. We proposed that the diminished
      response to beta-adrenergic stimulation may reflect abnormalities in Ca2+
      cycling, specifically alterations in the ability of the sarcoplasmic reticulum to
      effectively release and resequester Ca2+. We have used the unique combination of
      functional measurements on isolated, isometrically contracting papillary muscles
      from hearts of 26-week-old spontaneously hypertensive rats and their Wistar-Kyoto
      controls, together with electron probe microanalysis measurements of sarcoplasmic
      reticulum Ca2+ content in the same muscles after rapid freezing, to determine the
      availability of Ca2+ for activation of contraction, following beta-adrenergic
      stimulation. We observed a significant decrease in the inotropic response to beta
      adrenergic stimulation in papillary muscles from the spontaneously hypertensive
      rats, as compared with Wistar-Kyoto controls, however in these same muscles,
      frozen during relaxation, there was no evidence of an accompanying decrease in
      the size of the sarcoplasmic reticulum Ca2+ store. In an additional group of
      muscles which were frozen during contraction, the amount of Ca2+ remaining in the
      sarcoplasmic reticulum after stimulated release was also not different in the two
      strains. These results indicate that the decreased inotropic response to beta
      adrenergic stimulation in hypertrophied hearts of the spontaneously hypertensive
      rat is unlikely to be due to decreased availability of Ca2+ for activation of
      contraction. Additionally, to determine whether there is intracellular Ca2+
      overload in the cardiac muscle cells of hearts of spontaneously hypertensive
      rats, we measured the amount of Ca2+ in mitochondrial and at the level of the
      myofilaments by electron probe microanalysis. These results indicate that
      intracellular Ca2+ overload does not accompany cardiac hypertrophy in the
      spontaneously hypertensive rat. This study therefore shows no correlation between
      altered intracellular Ca2+ cycling and the decreased inotropic response to
      isoproterenol in the spontaneously hypertensive rat at 26 weeks of age.

PMID- 8576928
TI  - Effects of ryanodine on cardiac contraction, excitation-contraction coupling and
      "Treppe" in the conscious dog.
AB  - The effects of ryanodine on left ventricular (LV) function and hemodynamics were
      studied in 16 conscious dogs, chronically instrumented for measurements of LV
      pressures and dimensions. Systemic infusion of ryanodine (0.5-4 micrograms/kg
      i.v.) resulted in a dose-dependent depression of cardiac contraction. For
      example, ryanodine, 4 micrograms/kg i.v., decreased LV fractional shortening by
      30.5 +/- 4.1%, LV dP/dt by 41.5 +/- 4.0% and Vcfc by 37.8 +/- 4.1%, while
      increasing the isovolumic relaxation time constant, tau, from 23.1 +/- 1.4 to
      34.1 +/- 3.6 ms without a major effect on preload or afterload. Ryanodine also
      depressed (P < 0.05) the plateau phase of the mechanical restitution and post
      extrasystolic potentiation responses, indicating a direct effect on excitation
      contraction coupling. The heart rate dependent positive staircase ("Treppe") was
      significantly enhanced (P < 0.05) after ryanodine infusion, i.e. LV dP/dt rose by
      43.1 +/- 4.7% with an increase in heart rate from 150 to 240 beats/min in the
      presence of ryanodine 4 micrograms/kg, but by only 7.5 +/- 2.1% without
      ryanodine. The more pronounced "Treppe" in the conscious dog under the condition
      of impaired SR calcium release caused by ryanodine, supports the concept that the
      classical Bowditch "Treppe" reflects either a state of myocardial depression due
      to alteration in SR calcium handling, or enhanced availability of trans
      sarcolemmal Ca2+ influx. This finding may help to understand the discrepancy in
      the importance of the "Treppe" between conscious animals and more isolated
      preparations.

PMID- 8576929
TI  - Increased endothelin-1 gene expression in the endothelium of coronary arteries
      and endocardium in the DOCA-salt hypertensive rat.
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor and inotropic agent which may
      also induce cell hypertrophy. The role of ET-1 in ventricular hypertrophy in
      hypertension is unknown. We investigated ET-1 gene expression and immunoreactive
      ET-1 (ir-ET-1) concentration in the heart of deoxycorticosterone acetate (DOCA)
      salt hypertensive rats. To identify the cellular sites of ET-1 production in the
      heart, we performed in situ hybridization histochemistry. DOCA-treated rats which
      underwent unilateral nephrectomy (Uni-Nx) or not, exhibited mild systolic blood
      pressure elevation and ventricular hypertrophy. Blood pressure elevation and
      cardiac hypertrophy were more severe in DOCA-salt hypertensive rats. Ventricular
      ET-1 mRNA was similar in Uni-Nx control and DOCA-treated rats by Northern blot
      analysis, whereas in DOCA-salt hypertensive rats it was significantly increased.
      Ir-ET-1 concentration was also enhanced in ventricles from DOCA-salt hypertensive
      rats compared with Uni-Nx control rats. In situ hybridization histochemistry
      using a 35S-labelled complementary RNA ET-1 probe demonstrated that the level of
      ET-1 mRNA transcripts was increased exclusively in endothelial cells of large
      epicardial and small intramyocardial coronary arteries and in areas of the
      endocardium, but not significantly in myocardial cells of either the atria or
      ventricles. Enhanced ET-1 production may contribute to vascular changes, both
      structural and functional, in the heart in this model of hypertension in the rat,
      but probably does not contribute to the severe cardiac hypertrophy found in DOCA
      salt hypertensive rats.

PMID- 8576930
TI  - Differential stress protein mRNA expression during early ischaemic
      preconditioning in the rabbit heart and its relationship to adenosine receptor
      function.
AB  - The aim of this study was: (1) to elucidate in more detail the relationship
      between stress protein expression and brief periods of ischaemia and reperfusion,
      such as occur during early (classical) ischaemic preconditioning (PC) in the
      rabbit myocardium; (2) to determine whether stress protein expression is affected
      by adenosine receptor modulation, since adenosine is a mediator of the
      preconditioning response. We have studied the expression of the 60 kDa (hsp60);
      70 kDa (hsp70-inducible and constitutive isoforms) and 27 kDa (hsp27) stress
      proteins and the mitochondrial ATP-synthase beta-subunit using Northern blotting.
      Hsp60, hsp70 and hsp27 expression were also determined at the protein level by
      Western blotting. Total RNA and proteins were prepared from frozen samples of
      ischaemic left ventricle and non-ischaemic right ventricle rabbit myocardium
      after the following treatments (1) sham-operated; (2) 15 min stabilization + 5
      min coronary occlusion + 10 min reperfusion (PC); (3) PC + 30 min coronary
      occlusion (I); (4) PC + 30 min coronary occlusion + 2 h reperfusion (I/R) (5) the
      adenosine receptor antagonist 8-(p-sulpho-phenyl) theophyline (SPT) given 5 min
      prior to PC; (6) the adenosine receptor agonist 2-chlorocyclopentyl-N6-adenosine
      (CCPA) given in place of PC. A transient, approximately two-fold elevation in
      hsp60 mRNA occurred following 5 min coronary occlusion + 10 min reperfusion (PC)
      which was stable during a subsequent 30 min ischaemia (I), but returned to
      baseline during the second (2 h) reperfusion (I/R). An inducible hsp70 mRNA
      species appeared within 10 min of the second (30 min) coronary occlusion (I)
      which continued to increase to high levels during the second (2 h) reperfusion
      (I/R). Hsp27 mRNA expression was not altered following PC or subsequent ischaemia
      and reperfusion (I/R). ATP synthase beta-subunit mRNA did not change during PC or
      I but decreased during the subsequent 2 h reperfusion (I/R). Western blot
      analysis showed no change in left ventricle ischaemic zone hsp60, hsp70i/hsc70 or
      hsp27 protein during PC compared to an approximately two-fold elevation of hsp70i
      24 h following whole body heat stress or 24 h following 4 x 5 min coronary
      occlusion (as reported by Marber et al., 1993). However, hsp70i, hsp60 and hsp27
      showed significant decreases in immunodetectable protein following subsequent
      ischaemia and reperfusion (I/R). SPT inhibited the increase in hsp60 mRNA
      following PC (P < or = 0.05), but had no effect on hsp70, hsp27 or ATP-synthase
      mRNA levels. Therefore, differential expression of mRNAs for hsp60 and hsp70
      occurred following ischaemia and reperfusion, with hsp70 mRNA expression
      involving a significant reperfusion-dependent component. CCPA had no effect on
      expression of mRNAs for hsp60, hsp70, hsp27 or ATP-synthase. We conclude that the
      early phase of adenosine receptor-dependent preconditioning in the rabbit heart
      is not mediated via stress protein expression. However, brief ischaemia and
      reperfusion resulted in differential changes in individual stress protein gene
      expression which may be due to different physiological and/or biochemical
      components of ischaemia and reperfusion in the heart. In addition, partial
      dependence of hsp60 expression on adenosine receptor modulation was observed.

PMID- 8576931
TI  - Evidence for nitric oxide generation in the cardiomyocytes: its augmentation by
      hypoxia.
AB  - Recent reports suggest that endothelial-dependent relaxant factor, recognized as
      nitric oxide (NO), reduces myocardial contractility. Here, we showed that both
      exposures to acetylcholine and bradykinin for 30 min increased cyclic guanylate
      monophosphate (cyclic GMP) in isolated rat cardiomyocytes. These increases in
      cyclic GMP were blunted by NW-nitro-L-arginine methyl ester (L-NAME), an
      inhibitor of NO synthase. Hypoxia augmented the cyclic GMP accumulation due to
      exposures to acetylcholine and bradykinin, which were blunted by L-NAME. The
      increases in cyclic GMP due to acetylcholine and bradykinin during normoxic and
      hypoxic conditions were not blunted by aminoguanidine, an inhibitor of inducible
      NO synthase. These findings revealed that NO is produced in cardiomyocytes due to
      stimulation of NO synthase and modulates their own guanylate cyclase, which was
      augmented by hypoxia. NO production, through NO synthase in cardiomyocytes, may
      constitute autocrine regulations of myocardial contractility and paracrine
      regulations of coronary vasodilation and platelet aggregation.

PMID- 8576932
TI  - Troponin C-mediated calcium sensitization by levosimendan accelerates the
      proportional development of isometric tension.
AB  - The effects of various calcium sensitizers on myosin-actin crossbridge kinetics
      were evaluated in intact, paced guinea-pig papillary muscle by analysing the
      velocity of the development of isometric tension (dT/dt) in detail. The effect on
      association (the whole sequence of events from troponin onward) and dissociation
      rates of crossbridges was estimated from the rising phase and from the early
      decay phase of the normalized dT/dt curve. Levosimendan, a calcium sensitizer
      acting through troponin C, accelerated the proportional association rate and
      decelerated the dissociation rate of crossbridges. The effect of levosimendan on
      crossbridge kinetics occurred before the peak twitch tension was achieved. Thus,
      the compound did not change the actual relaxation phase of twitch tension. Since
      the effect on the association was more pronounced than on the dissociation of
      crossbridges, levosimendan shifted the entire twitch tension curve to the left.
      Based on the dissociation rate analysis levosimendan seems to act preferentially
      as a calcium sensitizer at low concentrations. At high concentrations the
      phosphodiesterase III (PDE III) inhibitory properties of levosimendan modulated
      its effect on the early relaxation processes. In contrast, PDE III inhibition is
      probably the primary mechanism of action for MCI-154. Pimobendan, and EMD 53998
      at low concentrations, whereas their direct effects on crossbridge kinetics
      contributed to the positive inotropic action at high concentrations. The calcium
      sensitizing mechanisms of these compounds seemed to be based almost exclusively
      on the decelerating effect on dissociation of crossbridges.

PMID- 8576933
TI  - Requirement of glycolytic substrate for metabolic recovery during moderate low
      flow ischemia.
AB  - Low flow ischemia with stable hemodynamic function can result in partial
      metabolic recovery characterized by an increase in phosphocreatine (PCr). Prior
      data suggest that glycolytic production of adenosine triphosphate (ATP) may be
      critical for this recovery and that the ATP produced by oxidative phosphorylation
      alone may be insufficient. This study tested the hypotheses that, during moderate
      low flow ischemia, (a) metabolic recovery is dependent on glycolytic production
      of ATP, and, therefore, (b) a mitochondrial substrate such as pyruvate alone is
      inadequate to allow metabolic recovery. High energy phosphates, pH, and lactate
      release were measured during 2 h of moderate low flow ischemia. Hearts were
      perfused with either a glycolytic plus mitochondrial substrate (glucose, insulin
      and pyruvate) or a mitochondrial substrate alone (pyruvate). Flow reductions
      required to reduce PCr by approximately 8% resulted in stable and equal
      reductions of rate-pressure product in each group. PCr recovered fully during the
      ischemic period in control hearts with glycolytic substrate, associated with
      preservation of normal end-diastolic pressure, and increased lactate release
      during the first hour of ischemia. Reperfusion of these hearts restored
      hemodynamic function and increased PCr above baseline values. In contrast, the
      use of pyruvate alone as a substrate resulted in a progressive fall of PCr during
      ischemia, increased end-diastolic pressure, and no significant increase in
      lactate release. Reperfusion in these hearts restored hemodynamic function, but
      did not result in normalization of PCr. Both groups had significant reductions in
      ATP during ischemia. Recovery of PCr during ongoing moderate low flow ischemia is
      observed in the presence of mixed glycolytic and mitochondrial substrates
      (glucose, insulin and pyruvate) but is not observed with pyruvate as a sole
      mitochondrial substrate. These data support a critical role for glycolytic flux
      under these conditions, suggesting that ATP generated solely by oxidative
      phosphorylation is not sufficient to promote metabolic recovery or maintain
      diastolic function during moderate low flow ischemia.

PMID- 8576934
TI  - Co-expression of tissue inhibitor and matrix metalloproteinase in myocardium.
AB  - Matrix metalloproteinases (MMP) are present in the latent form in normal
      myocardium. To examine the stringent balance between MMP and tissue inhibitor of
      metalloproteinase (TIMP) and to determine whether MMP are secreted simultaneously
      and in co-ordination with their inhibitors, we analysed MMP and TIMP by
      immunological, isolation by gel-permeation and affinity chromatography, and
      enzymatic assays in tissues and extracts. Using antibodies to MMP-1 and TIMP-1,
      we found strong in situ staining of MMP-1 and TIMP-1 in tissues. The staining was
      uniform in the endo- and subendomyocardium as well as in the interstitial space.
      TIMP-1 was present wherever MMP-1 was localized. From the tissue extract,
      proteins were separated on a gel-filtration column (Sephacryl S-200) and analysed
      for MMP and TIMP activity by zymography as well as by using succinyl-Gly-Pro-Leu
      Gly-Pro-4-amido-7-methyl coumarin (Suc-GPLGP-AMC) as a selective fluorogenic
      substrate for collagenase. TIMP and MMP were further purified on collagen
      Sepharose affinity column. The results indicated that MMP activity was co-eluted
      with TIMP activity. MMP-1, MMP-2 and TIMP-1 were further analysed by Northern
      blot for mRNA levels in the heart, skin, lung, liver and kidney. Results
      suggested co-expression of MMP-1 and TIMP-1 at the transcription level in all
      tissues. The level of MMP-2 mRNA was specifically higher in the heart tissue,
      which suggests a role of MMP-2 in the integrity of cardiovascular structure. The
      study indicated that myocardium as well as other tissue have an endogenous
      inhibitory system, suggesting that the MMPs activity is co-ordinated by their
      inhibitors at both the gene and protein levels. Furthermore, MMP and TIMP were co
      expressed and were tightly regulated in maintaining the architecture of the
      interstitial tissue.

PMID- 8576935
TI  - TGF-beta modulates the synthesis of proteoglycans by myocardial fibroblasts in
      culture.
AB  - In this study we examined the production of proteoglycans by fibroblasts cultured
      from the left ventricular myocardium of normal adult rats. Various molecular
      species of proteoglycan were detected, either by labeling glycosaminoglycan
      chains with 35SO4 or by labeling the proteoglycan core protein with
      [35S]methionine. The medium of the cell cultures, which contained quantitatively
      most of the proteoglycans, appeared to consist mainly of biglycan, lesser amounts
      of decorin and proteoglycans of higher molecular weight. Biglycan and decorin
      were identified not only by the characteristic mobility of the intact protein and
      the core protein but also by immunolocation on Western blots. TGF-beta
      upregulated the synthesis of all these proteoglycans, coincident with elongation
      of glycosaminoglycan side chains observed for biglycan and decorin. The apparent
      molecular weight of the core protein of the two proteoglycans remained unaffected
      by TGF-beta. The results of these experiments suggest that with regard to
      proteoglycan synthesis and its regulation by TGF-beta, cultured fibroblasts
      originating from the myocardium share to a large extent the properties of
      cultured fibroblasts of other organs.

PMID- 8576936
TI  - Cultured human myocardial fibroblasts of pediatric origin: natural human
      interferon-alpha is more effective than recombinant interferon-alpha 2a in
      carrier-state coxsackievirus B3 replication.
AB  - Cultured human myocardial fibroblasts of pediatric origin seem to be a useful
      species-specific model for studying various heart diseases which involve the
      myocardial interstitium, for example enterovirus heart disease. Cells were
      propagated from small samples of human ventricular tissues (0.2 g) obtained from
      standard surgical procedure for the correction of Fallot-tetralogy. Cultured
      cells exhibited typical fibroblastoid morphology over a period of 4 months and
      were uniformly immunoreactive with a monoclonal antibody directed against prolyl
      4-hydroxylase, a marker enzyme of fibroblasts. Infection of cell cultures with
      coxsackievirus B3, a cardiotropic enterovirus, resulted in a typical carrier
      state type of virus persistence. Average virus titers of 2.3 x 10(5) plaque
      forming units/ml (SD = 9.9 x 10(4)) were maintained over a period of up to 10
      weeks by productive infection of about 8-10% of the cell population.
      Coxsackievirus B3 carrier cultures of human myocardial fibroblasts were used to
      evaluate in vitro the long-term antiviral effects of recombinant interferon alpha
      2a and natural human interferon-alpha. Recombinant interferon-alpha reduced virus
      yields by 90% with a concentration of 423 IU/ml, whereas with natural interferon
      alpha a 90% reduction of virus yields was achieved with concentrations as low as
      21 IU/ml. Antiviral effects of both recombinant and natural interferon-alpha were
      highly specific and not related to inhibition of cell-proliferation (< 50% with
      interferon-alpha concentrations as high as 6250 IU/ml). Since effective
      concentrations of interferon-alpha can be easily attained in vivo with
      subcutaneous application, interferon-alpha (in particular: natural interferon
      alpha) may become useful in the treatment of patients with enterovirus
      myocarditis and enterovirus induced dilated cardiomyopathy.

PMID- 8576937
TI  - Effects of long-term therapy with ACE inhibitors, captopril, enalapril and
      trandolapril, on myocardial energy metabolism in rats with heart failure
      following myocardial infarction.
AB  - Although pharmacological therapy with angiotensin converting enzyme (ACE)
      inhibitors has proved to be effective in patients with heart failure (HF), the
      experimental basis of this effect has not yet been addressed. In the present
      study, animals with HF were treated with an oral administration of 10 mg/kg/day
      captopril, 10 mg/kg/day enalapril and 3 mg/kg/day trandolapril from the 2nd to
      12th week after the operation. HF was induced by permanent occlusion of the left
      coronary artery of the rat at 2 mm from its origin. Treatment of the HF rats with
      the ACE inhibitors enhanced the decrease in mean arterial blood pressure,
      attenuated the rise in left ventricular end-diastolic pressure, an indirect
      marker of preload, and diminished the reduction in cardiac output and stroke
      volume indices of the HF animal. Treatment also reversed the reduction in ATP,
      creatine phosphate, creatine and the mitochondrial oxygen consumption rate of the
      viable left and right ventricles of the HF animal. The improvement of the cardiac
      output index and high-energy phosphate levels of the HF rat by the ACE inhibitors
      was associated with the recovery of the mitochondrial oxygen consumption rate. In
      sham-operated animals, treatment with the ACE inhibitors reduced mean arterial
      pressure and left ventricular systolic pressure, but not metabolic variables
      concerning myocardial energy metabolism. The present results provide evidence
      that ACE inhibitor therapy improves cardiac function and myocardial energy
      metabolism of experimental animals with chronic heart failure. The mechanism
      underlying the benefit of long-term treatment with ACE inhibitors is probably
      attributable to recovery or preservation of the mitochondrial function and
      reduction in preload.

PMID- 8576938
TI  - Molecular cloning of human cardiac troponin T isoforms: expression in developing
      and failing heart.
AB  - Troponin T, which links the troponin complex to tropomyosin, is found as multiple
      isoforms in the hearts of many animal species. Changes in isoform composition
      have been correlated with variation in myofilament sensitivity to calcium. In
      order to determine the origin of diversity of the cardiac troponin T (cTnT)
      isoforms indicated by existing protein data, we have determined the sequences and
      patterns of expression of mRNAs encoding troponin T in fetal and adult heart and
      those present in adult heart in end-stage failure. Three main regions of
      alternative splicing within the cTnT coding region were identified using reverse
      transcriptase polymerase chain reaction (RT-PCR). Alternatively spliced RNAs are
      developmentally regulated and some of the fetal forms are expressed in adult
      failing heart. The molecular structure of the spliced regions was determined from
      cloned cDNAs and RT-PCR products. In the 5' region of the mRNA, isoforms are
      generated by the inclusion or exclusion of 15-, 3- and 27-nucleotide (nt)
      sequences and by the inclusion or exclusion of a separate 3-nt sequence. In the
      3' region of the mRNA, alternative splicing involves a 9-nt sequence which can be
      present in full, in part or not at all. A further splicing site was identified in
      the central region involving a 234-nt sequence and resulting in rare but
      detectable mRNAs. This work demonstrates the complexity of cTnT RNA composition
      in human heart and provides the information necessary to address the function of
      cTnT isoforms in contraction.

PMID- 8576939
TI  - Protective effect of amiloride during hypothermic hyperkalemic preservation: a
      31P NMR study in isolated pig hearts.
AB  - To assess the possible role of Na+/H+ exchange in ischemia-reflow damage during
      cold preservation, pig hearts retrogradely perfused with Krebs-Henseleit (KH)
      bicarbonate buffer were arrested by increasing [K+] (to 17 mM), cooled (10
      degrees C) and subjected to no flow ischemia for 15 h in the absence (C, n = 5)
      and in the presence of 0.5 mM amiloride (A, n = 5). A was added 7 min prior to
      ischemia and removed after 3 min reflow. 31P nuclear magnetic resonance (NMR)
      spectra were continuously acquired and functional indices were assessed prior to
      and after ischemia. Before reflow, the levels of phosphocreatine (PCr), ATP,
      inorganic phosphate (Pi)+phosphomonoesters (PME) and cytosolic pH in C and A did
      not differ: C, 12 +/- 7, 56 +/- 13, 427 +/- 75% of initial and 5.90 +/- 0.20; A,
      15 +/- 4, 82 +/- 21, 371 +/- 60% and 5.90 +/- 0.19, respectively; no contracture
      occurred. Upon reflow with hyperkalemic buffer PCr recovery in A-treated hearts
      was greater than in C (73 +/- 21 v 49 +/- 13%, P < 0.05) and parallel increases
      in left ventricular end diastolic (LVEDP) and perfusion pressure took place in
      both groups, however these parameters remained lower in A-treated hearts. Upon
      switching to KH buffer the oxygen uptake rate (VO2) was higher in A than in C (79
      +/- 18 v 59 +/- 6%, P < 0.05) whereas the differences in the pressure-rate
      product (PRP, 51 +/- 21 in A v 38 +/- 11% in C) and LVEDP (16 +/- 11 in A v 24 +/
      7 mmHg in C) did not reach statistically significant levels. Adjusting LVEDP in
      both groups to the same levels (19 +/- 6 v 21 +/- 9 mmHg in C) by changing
      balloon volume resulted in significant difference in PRP (61 +/- 19% v 42 +/- 6%
      in C, P < 0.02). The coronary resistance measured in beating hearts remained
      lower in A than in C (34.5 +/- 3.0 v 57 +/- 11 mmHg/(ml/min g), P = 0.04). To
      estimate contractile and metabolic reserves post-ischemic heart were challenged
      by increasing [Ca2+] in the perfusate from 1.0 to 1.6 mM. PRP and VO2 increased;
      PRP reached 71 +/- 32 (A) and 54 +/- 10% (C) and VO2 remained higher in A: 90 +/-
      16 (A) v 62 +/- 4% (C) (P = 0.01) of preischemic levels. We suggest that Na+/H+
      exchange may contribute to ischemia-reflow damage during cold preservation of
      isolated pig hearts.

PMID- 8576940
TI  - Enrichment of G protein alpha-subunit mRNAS in the AV-conducting system of the
      mammalian heart.
AB  - We investigated the expression pattern of the heterotrimeric G proteins Gs alpha,
      Gi alpha-2 and Go alpha in rat and guinea-pig heart by in situ hybridization.
      Cryosections were hybridized with single-stranded 35S-cRNA probes complementary
      to subtype-specific sequences of the respective mRNAs. Hybridization signals were
      visualized by exposition to X-ray films and dipping autoradiography. The rank
      order of abundance was Gi alpha-2 approximately Gs alpha >> Go alpha. In general,
      G protein alpha-subunit mRNAs were evenly distributed in the heart including endo
      and epicardium, large vessels and valves. Go alpha-mRNA levels were
      significantly higher in atria than in ventricles. In contrast to the rather
      uniform labeling of working myocardium, expression of all three G proteins was
      enriched in small intramural blood vessels and in subendocardial Purkinje fibers
      of septum and papillary muscles. A more marked enrichment of Gs alpha-, Gi alpha
      2- and especially Go alpha-mRNA was seen in neuronal ganglionic cells in the
      atrial septum and posterior regions of the atrium. The main finding, however, was
      an enrichment of all three G protein mRNAs in the atrioventricular conductive
      tissue. The accumulation was strictly co-localized with acetylcholinesterase
      positive regions identified as the atrioventricular node, the bundle of His and
      the right and left bundle branches and was seen similarly in rat and guinea-pig
      hearts. Quantitative in situ hybridization revealed Gs alpha-, Gi alpha-2- and Go
      alpha-mRNA levels in the bundle of His to be 206 +/- 0.13%. 191 +/- 0.15% and 165
      +/- 0.06%, respectively, of that in the surrounding interventricular working
      myocardium. These findings indicate that heterotrimeric G proteins play an
      important role in modulation of electrical conductance in the heart.

PMID- 8576941
TI  - Inotropic agent vesnarinone inhibits cytokine production and E-selectin
      expression in human umbilical vein endothelial cells.
AB  - The cytokine modulating effects of inotropic agents on human umbilical vein
      endothelial cells (HUVEC) were investigated. Confluent HUVEC in 24-well plates
      were treated with inotropic agents and then stimulated with 10 ng/ml of human
      interleukin (IL)-1 beta. After 24 h of incubation, the cytokine levels in the
      culture supernatants were determined by specific enzyme-linked immunosorbent
      assay (ELISA) kits. Vesnarinone [OPC-8212; 3,4-dihydro-6-(4-(3,4
      dimethoxybenzoil)-1-piperazinyl)-2(1H)- quinolinone] at 26 mumol/l significantly
      suppressed the production of IL-6, granulocyte macrophage colony stimulating
      factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) induced by IL-1
      beta. Although 8 bromoadenosine 3'5' cyclic monophosphate (8Br-cAMP) at 100
      mumol/l also inhibited the production of these cytokines, the inhibitory effect
      was less marked than that of vesnarinone. Amrinone at 26 mumol/l and NKH477 at 10
      nmol/l also had a less marked inhibitory effect against the production of IL-6.
      Next, the inhibitory effect of inotropic agents against the expression of the
      adhesion molecules of HUVEC was measured by a cell ELISA method. Vesnarinone at
      26 mumol/l and NKH477 at 10 mumol/l, a water soluble forskolin derivative used as
      a positive control, both significantly inhibited the expression of E-selectin
      induced by 10 ng/ml of human tumor necrosis factor (TNF)-alpha. Amrinone at 26
      mumol/l did not inhibit the expression of E-selectin. The level of HUVEC cAMP
      induced by vesnarinone at 26 mumol/l was much lower than that induced by NKH477
      at 10 mumol/l. Moreover, according to a 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyl
      tetrazolium bromide (MTT) cell viability assay, vesnarinone did not affect the
      viability of HUVEC. The immunosuppressive effects of vesnarinone described above
      are not derived from either a cAMP elevating effect or a cytotoxic effect against
      HUVEC. Although the cytokine network in heart failure has not yet been
      elucidated, patients with congestive heart failure might benefit from the
      immunomodulating effects of inotropic agents.

PMID- 8576943
TI  - Decrease in beta 1-adrenergic and M2-muscarinic receptor mRNA levels and
      unchanged accumulation of mRNAs coding for G alpha i-2 and G alpha s proteins in
      rat cardiac hypertrophy.
AB  - During compensatory cardiac hypertrophy in the rat, hemodynamic overload induces
      a parallel decrease in the densities of both beta 1-adrenergic (beta 1-AR) and M2
      muscarinic (M2-MR) receptors in the left ventricle, but the total number of
      receptors remains unchanged. It is not known whether this reduction is
      transcriptionally or translationally regulated, or if the functionally closely
      linked alpha-subunits of G protein (G alpha s and G alpha i-2) partake in this
      regulation. In order to resolve these questions, the absolute concentrations of
      mRNAs for both receptors and for G alpha s and G alpha i-2 were quantified by
      slot blot analysis of the left ventricles of adult rats 5 weeks after aortic
      banding. The results showed a significant decrease of both receptor mRNA levels
      in hypertrophied left ventricle (beta 1-AR: -48%; M2-MR: -42%) that paralleled
      the reduction in receptor protein densities and was negatively correlated with
      the left ventricular weight/body weight ratio (LVW/BW). By contrast, the relative
      levels of G alpha s and G alpha i-2 mRNAs remained unchanged, and both
      accumulated proportionally to the increase in LVW/BW. These results show that the
      beta 1-AR and the M2-MR were pretranslationally regulated. This suggests the
      hypothesis that the corresponding genes do not follow the general increase in
      transcriptional activity. By contrast, the genes coding for G alpha s and G alpha
      i-2 may follow the general pattern of activation during hypertrophy. Receptors
      and coupling proteins belong to two different groups of genes that are controlled
      by distinct mechanisms of regulation.

PMID- 8576944
TI  - Ca(2+)-channel blockers modulate the expression of interleukin-6 and interleukin
      8 genes in human vascular smooth muscle cells.
AB  - Ca(2+)-channel blockers at therapeutic concentrations were shown to modulate
      several processes underlying inflammation, such as growth factor-mediated
      activation of genes coding for the low density lipoprotein receptor and 3-hydroxy
      3-methylglutaryl coenzyme A (HMG-CoA) reductase in human vascular smooth muscle
      cells (VSMC) (Block et al., 1991), and for interleukins in human mesangial cells
      (Roth et al., 1992). Two Ca(2+)-channel blockers, Manidipine (Roth et al., 1992)
      and Verapamil (Walz et al., 1990) have been shown to induce the expression of the
      gene coding for interleukin-6 (IL-6). Here we demonstrate that the four Ca(2+)
      channel blockers, Amlodipine, Felodipine, Isradipine and Manidipine, at nanomolar
      concentrations, activate the transcription of the genes encoding IL-6 and IL-8 in
      primary human VSMC and fibroblasts. Ca(2+)-channel blocker-induced transcription
      is subsequently followed by secretion of the two ILs into the growth medium of
      the cells. In addition, we compared the action of the Ca(2+)-channel blockers
      with that of propranolol, a beta-adrenoceptor antagonist, or with furosemide, a
      diuretic, all of which are known to lower blood pressure. However, in contrast to
      the dihydropyridines, the two latter drugs failed to affect the expression of the
      two IL genes.

PMID- 8576942
TI  - Complete primary structure of chicken cardiac C-protein (MyBP-C) and its
      expression in developing striated muscles.
AB  - C-protein (MyBP-C) is a myosin binding protein of about 140 kDa which is known to
      modulate myosin assembly in striated muscles. A cardiac-type isoform of C-protein
      appears not only in cardiac muscle but also in skeletal muscle before skeletal
      muscle-type isoforms become detectable during myogenesis, suggesting that the
      cardiac isoform is involved in the early phase of myofibrillogenesis (Bahler et
      al., 1985; Kawashima et al., 1986). In this study, in order to understand the
      structure and functional domains of the cardiac-type C-protein, we cloned and
      sequenced full-length cDNAs encoding chicken cardiac C-protein from lambda gt11
      cDNA libraries which were prepared with poly (A)+ RNA from embryonic chicken
      cardiac muscle as well as embryonic chicken skeletal muscle by using antibodies
      specific for cardiac C-protein. Two cDNA variants, probably generated by
      alternative RNA splicing and encoding different C-protein isoforms, were
      detected. As judged by the cDNA sequences determined, overall homology of the
      peptide sequence between cardiac and skeletal muscle C-proteins (Einheber et al.,
      1990; Furst et al., 1992, Weber et al., 1994) was about 50-55%. Like other myosin
      binding proteins, skeletal C-proteins, 86 kDa protein and M-protein, cardiac C
      protein contains several copies of fibronectin type III motifs and immunoglobulin
      C2 motifs in the molecule, but their number and arrangements differed somewhat
      from those in the other proteins. Northern blot analysis with the cloned cDNA as
      a probe demonstrated that mRNA of 5.0 kb is transcribed in both cardiac and
      embryonic skeletal muscle, and that it is specifically expressed in cardiac
      muscle among adult tissues.

PMID- 8576946
TI  - Adrenergic desensitization in left ventricle from streptozotocin diabetic swine.
AB  - Patients with diabetes mellitus that exhibit cardiac pump failure display
      compromised stroke volume, ejection fraction, and slower rates of rise and fall
      of left ventricular (LV) dP/dt in the absence of ischemic injury. We hypothesized
      that diabetic cardiomyopathy may involve decrements in adrenergic sensitivity,
      with specific molecular alterations in the beta-adrenergic receptor (beta AR)- G
      protein- adenylyl cyclase (AC) signal transduction system. We assessed the
      effects of 3 months of streptozotocin-induced diabetes (125 mg/kg i.v.; DIAB, n =
      10) on myocardial signal transduction in mini-pigs. DIAB were hyperglycemic
      compared to controls (CON, n = 10; 20.92 +/- 2.64 v 5.24 +/- 0.35 mM glucose),
      and had lower fasting insulin levels (6.46 +/- 0.97 v 13.68 +/- 3.91 microU/ml).
      Transmural LV free wall homogenates from DIAB exhibited similar beta AR density
      as CON, but decreased cAMP production (pmol cAMP/mg prot.min) using these
      pharmacological stimulators: 10 microM Isoproterenol plus 100 microM GTP (74 +/-
      5 v 97 +/- 11); 100 microM Gpp(NH)p (116 +/- 7 v 161 +/- 17); 10 mM fluoride ion
      (266 +/- 16 v 324 +/- 25). No differences between DIAB and CON were observed when
      stimulated by 100 microM forskolin (440 +/- 20 v 429 +/- 33), suggesting no
      alterations in the catalytic subunit of AC. In DIAB, quantitative immunoblotting
      indicated slightly depressed levels of Gs (552 +/- 44 v 630 +/- 59 pmol/g ww;
      NS), but a significant redistribution of alpha s from the sarcolemma to the
      cytosol (32.7 +/- 0.82% v 25.9 +/- 1.7%). Significantly elevated levels of
      cardiac Gi were seen in DIAB homogenates compared to CON ventricles (2326 +/- 145
      v 1522 +/- 181 pmol/g ww), with no alpha i subunit redistribution. We conclude
      that despite maintained beta AR density, receptor-dependent and G protein
      dependent stimulation of AC is depressed so that streptozotocin-induced diabetic
      LV is affected by increased cardiac Gi, redistribution of Gs alpha to the
      cytosol, and an increase in the Gi/Gs ratio. These results help explain depressed
      catecholamine responsiveness and cardiac performance exhibited by diabetic
      patients.

PMID- 8576945
TI  - Effect of dietary antioxidant trace element supply on cardiac tolerance to
      ischemia-reperfusion in the rat.
AB  - Over a 10-week period, female Wistar rats received a diet containing various
      levels of four trace elements (Zn, Cu, Mn, Se), co-factors of antioxidant enzymes
      (superoxide dismutase SOD, glutathione peroxidase GPx), in order to examine the
      influence of supplementation or deficiency of these elements (i) on tissue
      antioxidant enzyme defence systems, and (ii) on the susceptibility of the
      myocardium to ischemia-reperfusion injury. At the end of the dietary treatment,
      hearts were perfused at constant flow (11 ml/min) before being subjected to 15
      min of total global normothermic ischemia, followed by reperfusion. The effects
      of the various diets (deficient, standard or supplemented) were estimated by
      studying functional recovery of various cardiac parameters (left ventricular
      developed pressure LVDP, dP/dtmax, heart rate x LVDP) as well as ultrastructural
      tissue characteristics. Furthermore, SOD and GPx activities were measured before
      ischemia and at the end of the reperfusion period. Results suggest that: (a) the
      activity of antioxidant enzymes increased or decreased significantly when diet
      was respectively supplemented with, or deficient in, trace elements, but was not
      further modified by an ischemia-reperfusion episode: (b) the recovery of cardiac
      function during reperfusion, and ventricular myocardial ultrastructure were
      significantly improved under the influence of trace element supplementation when
      compared to both standard and deficient groups. These results illustrate the
      protective effect of trace elements which are co-factors of antioxidant enzymes
      in limiting ischemia-reperfusion induced injury, and suggest a possible use in
      the field of anti-ischemic therapy.

PMID- 8576947
TI  - Cardiac endothelin-1 content and receptor subtype in spontaneously hypertensive
      rats.
AB  - Endothelin-1 (ET-1), a newly discovered peptide with potent vasoconstrictor and
      growth-promoting effects, has been implicated in high blood pressure and cardiac
      hypertrophy in the spontaneously hypertensive rat (SHR). In the present study, we
      measured plasma ET-1 levels and tissue ET-1 concentrations in the four cardiac
      chambers of 17- to 18-week-old SHR and their normotensive controls. Wistar Kyoto
      (WKY) rats. SHR had slightly but significantly higher plasma ET-1 levels than
      WKY. The ventricles had the highest ET-1 content and the atria in both strains
      had the highest ET-1 concentrations. ET receptor subtypes were analysed by
      radiogand binding with ET-1, BQ-123 and IRL 1620 in crude membrane preparations
      of the four cardiac chambers. No differences in receptor subtype densities or
      affinities were apparent between the two strains. ET(A) represented 75 to 85% of
      both ET receptors. Competition analysis revealed that in both strains left
      ventricular tissue had lower receptor densities and higher affinities than the
      atria. These results suggest that ET-1 and its receptor although contributing in
      the maintenance of high blood pressure may not be an important factor during
      stable cardiac hypertrophy in adult SHR. The differential distribution of ET-1
      content and receptor densities favoring the atria in both strains suggest that
      this peptide may have a different physiological role in the atria from that in
      the ventricles.

PMID- 8576948
TI  - Aggregation of myocardial sarcolemmal transmembrane proteins is not hindered by
      an interaction with the cytoskeleton. Possible implications for ischemia and
      reperfusion.
AB  - Heart myocytes subjected to ischemia show a clustering of the sarcolemmal
      proteins. In the erythrocyte membrane, a system in which intramembranous particle
      (IMP) aggregation is extensively studied, it is found that an IMP aggregation can
      in principle only occur upon removal of the membrane skeleton of spectrin and
      actin by rather drastic experimental conditions. With regard to phospholipid
      composition and topology the sarcolemma and the erythrocyte membrane show large
      similarities and therefore it was proposed that a loss of the interaction of the
      IMPs and the cytoskeleton is also a prerequisite for the sarcolemmal IMP
      aggregation (Verkleij et al., 1990). Freezing myocardial tissue, both from adult
      and neonatal rat, from temperatures lower than 37 degrees C resulted in an
      aggregation of the sarcolemmal IMPs. The aggregation is proportional to the
      degree of lowering of the temperature at which the tissue is cryofixed. This in
      contrast to the erythrocyte membrane, where lowering the temperature only induces
      moderate IMP aggregation. The IMP aggregation in the sarcolemma is reversible
      upon a subsequent increase in incubation temperature. The results clearly
      demonstrate that the interaction between the sarcolemmal proteins does not hinder
      aggregation of the IMPs, as proposed previously, and suggest that loosening of
      this complex does not have to proceed the aggregation of the sarcolemmal
      intramembranous particles during ischemia.

PMID- 8576949
TI  - Angiotensin II stimulates the autocrine production of transforming growth factor
      beta 1 in adult rat cardiac fibroblasts.
AB  - Angiotensin II (Ang II) has been implicated in the development of cardiac
      hypertrophy and myocardial fibrosis. While recent in vivo and in vitro studies
      performed in cultured cardiac myocytes and fibroblasts support this role for Ang
      II, the mechanisms of Ang II action at the cellular level remain unclear. In the
      present study, we postulated that Ang II action in adult cardiac fibroblasts may
      stimulate the autocrine production and release of transforming growth factor-beta
      1 (TGF-beta 1), a known regulator of cardiac fibroblast and myocyte function. We
      examined the ability of Ang II to regulate the gene expression, biological
      activity, and protein production of TGF-beta 1 in cultured adult rat cardiac
      fibroblasts. Treatment of fibroblast cultures with Ang II (10(-9) M) induced a
      two-fold increase in TGF-beta 1 mRNA levels within 4 h that was sustained through
      24 h (P < 0.01). TGF-beta 1-like activity in Ang II-treated cultures was
      significantly increased compared with control as measured by bioassay (P <
      0.001). Specificity for TGF-beta 1-like activity was confirmed through its
      neutralization with a TGF-beta 1 specific antibody (100 micrograms/ml). Total
      concentration of TGF-beta 1 (latent plus active forms) in conditioned media from
      Ang II-treated cardiac fibroblasts was also found to be greater than control (P <
      0.01). These findings suggest that the effects of Ang II in the adult myocardium
      may be mediated in part by autocrine/paracrine mechanisms, including the
      production and release of TGF-beta 1 by cardiac fibroblasts.

PMID- 8576950
TI  - Adaptational response in transcription factors during development of myocardial
      hypertrophy.
AB  - Cardiac hypertrophy is characterized, among others, by the molecular events which
      selectively activate the expression of genes for contractile proteins within
      individual myocardial cells. As such, myosin light chain 2 (MLC-2), which is
      upregulated in the hypertrophic state in both rat and human, serves as a marker
      for hypertrophy. In an attempt to investigate the gene regulatory mechanisms of
      this phenomenon, we tested the hypothesis that certain transcription factors are
      directly involved in the development of cardiac hypertrophy by demonstrating the
      presence of cardiac tissue-specific regulatory elements in the 5'-flanking region
      of the MLC-2 promoter and testing them in the gel mobility shift assay for their
      binding activity to nuclear proteins from hypertrophied and normal cardiac
      tissue. In nuclear extracts from the ventricular tissues of the spontaneously
      hypertensive rat (SHR), distinctive changes in two families of activator
      proteins, the A/T-rich DNA-binding transcription factors, myocyte enhancer factor
      (MEF-2) and CArG-binding factor, manifested in a developmentally dictated manner
      paralleling the evolution of cardiac hypertrophy in these animals. Extracts
      isolated from brains and skeletal muscle tissues from the same animals did not
      exhibit the changes in binding activity. Also, the changes were not apparent when
      a distal negative regulatory element (CSS), which confers cardiac-specific
      expression, was tested in gel mobility shift assays. The ubiquitous TATA-binding
      proteins remained unchanged in comparing SHR with the control strain WKY in the
      same assay. These data support the notion that the expression of specific
      transcription factors is modulated in response to hypertrophy related signals
      which execute changes at the gene level effecting the enrichment of certain
      contractile proteins in an effort discrete and estranged from the basal
      transcription machinery.

PMID- 8576951
TI  - Endogenous adenosine reduces depression of cardiac function induced by beta
      adrenergic stimulation during low flow perfusion.
AB  - High levels of norepinephrine in the heart are cardiotoxic resulting in
      contractile dysfunction and arrhythmic activity via beta-adrenoceptor mediated
      mechanisms. A low flow heart model perfused with physiological saline containing
      glucose and bubbled with an O2 gas mixture was used to determine whether
      adenosine, a nucleoside with antiadrenergic properties, could reduce the
      functional manifestations of catecholamine cardiotoxicity. Isolated rat hearts
      were treated with dipropylcyclopentylxanthine (DPCPX; 0.1 microM; A1 receptor
      antagonist) to block endogenous adenosine. In DPCPX-treated hearts stimulated
      with isoproterenol (ISO; 1 microM) during 45 min of low flow (0.5 ml/min)
      perfusion, the recovery of contractile function (ConF) at 15 min after the
      restoration of normal flow was 64% of control (before low flow) values as
      compared to 110% recovery of ConF in the absence of ISO. The incidence of
      arrhythmias observed upon restoration of control flow was increased by ISO when
      the action of endogenous adenosine was blocked with DPCPX. In the absence of
      DPCPX both the functional depression and arrhythmias induced by ISO were
      prevented in the presence of phenylisopropyladenosine (PIA; 1 microM; A1 receptor
      agonist). At 15 min after normal flow was restored. ConF in ISO-treated hearts
      with PIA was 53% greater than in the absence of PIA and presence of DPCPX. This
      enhancement of ConF by PIA was significantly reduced by DPCPX. By 30 min after
      flow restoration, these significant differences were absent. DPCPX reversed the
      PIA-induced reduction in arrhythmias observed upon restoration of normal flow.
      PIA and DPCPX alone in the absence of ISO, and ISO in the absence of PIA and
      DPCPX, did not result in altered ConF upon restoration of normal flow. These
      findings indicate that intense beta-adrenergic stimulation of the heart during
      low-flow perfusion in the absence of adenosine A1 receptor activity induces
      contractile depression and arrhythmicity subsequent to restoration of control
      perfusion. It is concluded that endogenous adenosine protects the heart against
      catecholamine toxicity via stimulation of adenosine A1 receptors.

PMID- 8576952
TI  - DNA typing of HLA class II genes in Japanese patients with dilated
      cardiomyopathy.
AB  - HLA class II genes (DRB, DQA, DQB, DPA, and DPB) were typed at the DNA level
      using polymerase chain reaction/sequence-specific oligonucleotide probe analysis
      in 78 unrelated patients with DCM and 336 unrelated healthy controls to elucidate
      the HLA alleles or HLA haplotypes associated with DCM. The frequencies of
      DRB1*1401 (15.4% v 4.5%, RR = 3.90, P < 0.0005, Pc < 0.03), DQB1*0503 (14.1% v
      5.4%, RR = 2.93, P < 0.007) and DRB1*1401-DQB1*0503 haplotype (11.5% v 1.5%, RR =
      8.24, P < 0.00001, Pc < 0.01) were increased in the DCM patients. The frequency
      of HLA-DRB1*1101 (9.0% v 3.0%, RR = 3.26, P < 0.02) also was increased in the
      patients. In addition, the frequencies of DQB1*0604 and DPB1*0401 were increased
      in the DRB1*1401 and DRB1*1101 negative patients. In contrast, the frequencies of
      DQB1*0303 (19.2% v 30.7%, RR = 0.55, P < 0.05) and DRB1*0901-DQB1*0303 haplotype
      (16.7% v 29.8%, RR = 0.49, P < 0.02) were decreased in the DCM group. Disease
      susceptibility to DCM in the Japanese population, thus, may be controlled in part
      by a gene (or genes) in close linkage disequilibrium with DRB1*1401-DQB1*0503,
      DRB1*1101-DQB1*0301, and DQB1*0604-DPB1*0401 haplotypes, while the resistance to
      DCM may be associated with the DRB1*0901-DQB1*0303 haplotype.

PMID- 8576953
TI  - Isolation of neonatal cardiomyocytes reduces the expression of the GTP-binding
      protein, Gh.
AB  - alpha 1-Adrenoceptors in most tissues couple with the heterotrimeric GTP-binding
      protein Gq, the alpha subunit of which activates the beta-isoforms of
      phospholipase C. However, in heart (and in liver) alpha 1-adrenoceptors have been
      reported to couple to a high molecular weight GTP-binding protein. Gh, which
      functions both as a type II transglutaminase and as a receptor coupling protein.
      Gh activates a phospholipase isoform distinct from phospholipase C-beta. Here we
      report that isolation and culture of neonatal cardiomyocytes decreased the
      expression of Gh without reducing the content of Gq or Gi. Gh was readily
      detected in extracts from intact neonatal and adult heart tissues. The expression
      of Gh thus appears to be a feature of intact cardiac tissue.

PMID- 8576954
TI  - Differential sensitivity of C2-C12 striated muscle cells to lovastatin and
      pravastatin.
AB  - One of the major side-effects of the use of HMG CoA reductase inhibitors for the
      treatment of hypercholesterolemia is the development of myositis and, in some
      patients undergoing concomitant immunosuppressive treatment, the development of
      rhabdomyolysis. Experiments outlined in these studies demonstrate that inhibitors
      of HMG-CoA reductase activity which differ primary in the substitution of a
      methyl group for a hydroxyl group have differential effects on both cholesterol
      levels and cell viability in a striated muscle cell model, the mouse C2-C12
      myoblast. Thus, concentrations as high as 200 microM of pravastatin had little
      effect on total cholesterol level while 25 microM of lovastatin decreased
      cellular cholesterol by over 90%. Simvastatin and lovastatin decreased viability
      of C2-C12 myoblasts by nearly 50% at concentrations as low as 1 and 5 microM,
      respectively, and decreased viability by almost 90% at 10 and 15 microM
      respectively. However, 300 microM of pravastatin decreased cell viability by less
      than 50%. The order of potency for the effects on cell viability
      wassimvastatin>lovastatin>>>pravastatin. The possible relationship between
      effects on cell viability and the development of myositis is discussed.

PMID- 8576955
TI  - Chloride conductance in human atrial cells.
AB  - Many types of chloride current have been reported in the hearts of various
      species; however, the nature of chloride conductance in the human heart is still
      unclear. We investigated cyclic AMP-dependent chloride current and swelling
      induced chloride current in isolated human atrial cells using the whole-cell
      voltage-clamp method. External application of 1 microM isoprenaline increased
      calcium current by 391.9 +/- 48.6% (mean +/- S.D., n = 8); however, there was no
      activation of cyclic AMP-dependent chloride current at steady-state membrane
      potentials between -80 and +50 mV. Neither external application of 10 microM
      forskolin nor internal application of 50 microM cyclic AMP activated a cyclic AMP
      dependent chloride current. On the other hand, when the same cell was superfused
      with a 50% hypotonic solution, it exhibited osmotic swelling and an outward
      rectifying current (6.59 +/- 0.96 pA/pF at +30 mV, n = 10). This swelling-induced
      current reversed at -26.5 +/- 3.1 mV (n = 10), close to the calculated
      equilibrium potential for chloride, and it was sensitive to the stilbene
      derivative chloride channel blocker. In conclusion, no activation of cyclic AMP
      dependent chloride current was observed in human atrial cells. On the other hand,
      a swelling-induced chloride current was consistently demonstrated and its kinetic
      properties were similar to those reported in other cardiac myocytes.

PMID- 8576956
TI  - Isolation and characterization of a 1 Mb region of 5q23.3-q31.2 surrounding the
      human lysyl oxidase gene.
AB  - Lysyl oxidase (EC 1.4.3.13) plays a pivotal role in the maintenance of tissue
      integrity in both the normal and pathological states. It is a member of a newly
      discovered gene family that exhibits a complex mode of regulation. To date the
      resources necessary to begin to address its regulation have not been assembled.
      In part, this reflects the instability of this region of the genome when cloned
      into cosmid vectors. The paucity of long range restriction endonuclease sites
      suitable for mapping this region of the genome has further hampered progress. To
      begin to address this issue 2 YAC clones of 920 kb and 245 kb that contain the
      human lysyl oxidase gene were isolated. Long range physical mapping revealed that
      the 245 kb clone was centrally located within the 920 kb clone. The corresponding
      map of this region is congruent with that observed in the human genome. Thus,
      these YACs faithfully represent this region of the human genome. The results of
      our cloning and mapping studies described in this communication should accelerate
      the advance of our understanding of this new connective tissue gene family.

PMID- 8576957
TI  - The norepinephrine-stimulated inositol phosphate response in human atria.
AB  - Inositol phosphate release and metabolism were studied in right atrial appendages
      obtained from 18 patients undergoing coronary artery bypass surgery and/or mitral
      valve replacement. [3H]Inositol-labeled human atria contained inositol(1,4.
      5)trisphosphate, inositol(1,4)bisphosphate and the 1- (or 3) and 4-isomers of
      inositol monophosphate. Addition of norepinephrine (100 mumol/l) activated the
      release of inositol phosphates, as indicated by increased [3H]inositol label in
      all of these inositol phosphates. However, the phosphorylation product of
      inositol (1.4.5)trisphosphate, inositol-(1,3,4,5)tetrakisphosphate, and its
      metabolic products were not detected, either in control or stimulated atria.
      Similar inositol phosphate profiles were observed in rat right atria.
      Furthermore, both human and rat atria contained high concentrations of
      inositol(1,4,5)trisphosphate, which were not observed to increase with
      norepinephrine stimulation. The inositol phosphate responses to norepinephrine in
      rat and human cardiac tissue appear to be similar, except for the generally lower
      activity observed in human tissue. Thus, the rat provides a suitable model for
      the study of cardiac phosphatidylinositol turnover.

PMID- 8576958
TI  - The role and amplification of the HS Alu subfamily founder gene.
AB  - A recently identified Alu element (Leeflang et al. J. Mol. Evol. 1993, 37:559
      565), referred to as the "putative founder of the HS (PV) subfamily," was found
      to be present at orthologous loci in the human, chimpanzee, gorilla, and gibbon
      lineages. The evolution of this Alu suggested that it is a source gene in the
      evolution of Alu family repeats for one of the most recent subfamilies, HS. We
      have determined that this putative founder of the HS subfamily was not present at
      the orthologous loci in older primates, including old world and new world
      monkeys. Thus, this particular Alu locus has only been responsible for the
      establishment of a very small subfamily of Alu sequences. We have further
      demonstrated that this putative founder Alu was not responsible for the de novo
      Alu insertion into the neurofibromatosis-1 gene of an individual causing
      neurofibromatosis. Our data demonstrate that although the putative founder of the
      HS subfamily found by Leeflang et al. (1993) probably gave rise to one of the
      most recent subfamilies of Alu sequences, it has not been very active in
      retroposition.

PMID- 8576959
TI  - Genetic variation of recent Alu insertions in human populations.
AB  - The Alu family of interspersed repeats is comprised of over 500,000 members which
      may be divided into discrete subfamilies based upon mutations held in common
      between members. Distinct subfamilies of Alu sequences have amplified within the
      human genome in recent evolutionary history. Several individual Alu family
      members have amplified so recently in human evolution that they are variable as
      to presence and absence at specific loci within different human populations.
      Here, we report on the distribution of six polymorphic Alu insertions in a survey
      of 563 individuals from 14 human population groups across several continents. Our
      results indicate that these polymorphic Alu insertions probably have an African
      origin and that there is a much smaller amount of genetic variation between
      European populations than that found between other population groups.

PMID- 8576960
TI  - Standardized nomenclature for Alu repeats.

PMID- 8576961
TI  - Flanking sequences of an Alu source stimulate transcription in vitro by
      interacting with sequence-specific transcription factors.
AB  - An Alu source gene, called the EPL Alu, was previously isolated by a phylogenetic
      strategy. Sequences flanking the EPL Alu family member stimulate its RNA
      polymerase III (Pol III) template activity in vitro. One cis-acting element maps
      within a 40-nucleotide region immediately upstream to the EPL Alu. This same
      region contains an Ap1 site which, when mutated, abolishes the transcriptional
      stimulation provided by this region. The flanking sequence, as assayed by gel
      mobility shift, forms sequence-specific complexes with several nuclear factors
      including Ap1. These results demonstrate that an an ancestral Alu source sequence
      fortuitously acquired positive transcriptional control elements by insertion into
      the EPL locus, thereby providing biochemical evidence for a model which explains
      the selective amplification of Alu subfamilies.

PMID- 8576962
TI  - SINE and LINE within human centromeres.
AB  - A number of the Alu and L1 elements present within the centromeric regions of the
      human chromosomes have been analyzed by polymerase chain reaction amplification.
      The oligonucleotide primers were homologous to the 3' end consensus sequences of
      either Alu or L1 in conjunction with an oligonucleotide primer homologous to
      alphoid sequences specific to different chromosomes. This allowed one to detect
      an unusual number of Alu and L1 polymorphisms at different loci. It is proposed
      that this results from molecular rearrangements which occur within the alpha
      satellite DNA in which they are embedded (Marcais et al. J. Mol. Evol. 33:42-48,
      1991) and not because the centromeric regions are targets for new insertions of
      such elements. The same analyses were made on cosmids and YACs originating from
      the centromeric region of chromosome 21 as well as on a collection of somatic
      hybrids containing chromosome 21 centromere as unique common human genetic
      material. The results were consistent with the above hypothesis.

PMID- 8576963
TI  - Retrotransposon Mys was active during evolution of the Peromyscus leucopus
      maniculatus complex.
AB  - Mys is a retrovirus-like transposable element found throughout the genus
      Peromyscus. Several mys subfamilies identified on the basis of restriction site
      variation occur in more than one species. The distribution of these subfamilies
      is consistent with the accepted species phylogeny, suggesting that mys was
      present in the ancestor of Peromyscus and has been active through much of the
      evolution of this genus. Quantitative Southern blot analysis was used to examine
      the variability of subfamilies in P. leucopus and maniculatus. We found that
      subfamilies with phylogenetically narrow distributions were more variable in copy
      number both within and between species than subfamilies with a broader
      distribution. Taken together, our data suggest that mys has undergone multiple
      rounds of transposition since the peromyscine radiation, and that five
      subfamilies have been amplified during the evolution of the leucopus-maniculatus
      species complex.

PMID- 8576964
TI  - Computer simulation of transposable element evolution: random template and strict
      master models.
AB  - It has been proposed that the most extensively studied mammalian retrotransposons
      replicate by some form of a master template model. This conclusion has been drawn
      largely from DNA sequence analysis and is based on phylogenetic tree topology,
      the presence and ordering of shared variants, the degree of divergence between
      elements within a subfamily, and the shape of the distribution of pairwise
      differences between elements. To investigate how robust these parameters are as
      predictors of the model of transposition, computer simulations of the two most
      extreme transposition models, the Random Template Model and the Strict Master
      Model, were carried out. A prototype of a computer simulator for studying
      retrotransposition is presented. The simulator is a versatile digital workbench
      that maintains DNA sequence data and allows manipulation of a range of factors
      including reverse transcriptase and in situ mutation rates, transposition
      template, and transposition rate. All parameters previously used as predictors of
      the model of transposition were markedly different for the two extreme models
      when evaluated using large sample sizes of sequences from experiments simulating
      up to 15 million years of evolution.

PMID- 8576965
TI  - The age of Alu subfamilies.
AB  - Using Kimura's distance measure we have calculated the average age of all major
      Alu subfamilies based on the most recent available data. We conclude that AluJ
      sequences are some 26 Myr older than previously thought. Furthermore, the origin
      of the FLA (Free Left Arm) Alu family can be traced back to the very beginning of
      the mammalian radiation. One new minor subfamily is reported and discussed in the
      context of sequence diversity in major Alu subfamilies.

PMID- 8576966
TI  - Mosaic evolution of rodent B1 elements.
AB  - We have determined sequences of PCR-amplified B1 elements from hamster and rat
      (Myomorpha), chipmunk (Sciuromorpha), and guinea pig (Caviomorpha). Between three
      and six B1 subfamilies were found in these species. In the phylogenetic analysis
      B1 sequences of hamster, mouse, and rat clustered separately from those of
      chipmunk and those of guinea pig. This is consistent with an independent
      evolution of B1 elements in separate rodent lineages. We exclude the possibility
      of convergent mutations to explain certain diagnostic characters within the
      modern B1 quasi-dimers and view these elements as mosaic structures assembling
      preexisting mutations. Furthermore, the presence of Alu-like structural motifs
      supports the hypothesis of the monophyletic origin of Alu and B1 repeats, i.e.,
      from a common 7SL RNA-derived retroposing monomeric element.

PMID- 8576967
TI  - Sporadic amplification of ID elements in rodents.
AB  - ID sequences are members of a short interspersed element (SINE) repetitive DNA
      family within the rodent genome. The copy number of individual ID elements varies
      by up to three orders of magnitude between species. This amplification has been
      highly sporadic in the order Rodentia and does not follow any phylogenetic trend.
      Using library screening and dot-blot analysis, we estimate there are 25,000
      copies of ID elements in the deer mouse, 1,500 copies in the gerbil (both
      cricetid rodents), and 60,000 copies of either ID or ID-like elements in a
      sciurid rodent (squirrel). By dot-blot analysis, we estimate there are 150,000,
      4,000, 1,000, and 200 copies of ID elements in the rat, mouse, hamster, and
      guinea pig, respectively (which is consistent with previous reports) and 200
      copies in the hystricognath rodent, nutria. Therefore, a rapid amplification took
      place not only after the divergence of rat and mouse but also following the deer
      mouse (Peromyscus) and hamster split, with no evidence of increased
      amplifications in hystricognath rodents. No notable variations of sequences from
      the BC1 genes of several myomorphic rodents were observed that would possibly
      explain the varied levels of ID amplification. We did observe subgenera and
      species-group-specific variation in the ID core sequence of the BC1 gene within
      the genus Peromyscus. Sequence analysis of cloned ID elements in Peromyscus show
      most ID elements in this genus arose prior to Peromyscus subgenus divergence.
      Correspondence of the consensus sequence of individual ID elements in gerbil and
      deer mouse further confirms BC1 as a master gene in ID amplification. Several
      possible mechanisms responsible for the quantitative variations are explored.

PMID- 8576968
TI  - Ultrasound, what every trauma surgeon should know.

PMID- 8576969
TI  - A locked hip screw-intramedullary nail (cephalomedullary nail) for the treatment
      of fractures of the proximal part of the femur combined with fractures of the
      femoral shaft.
AB  - Twenty-seven patients with complex femoral fractures (combined shaft and proximal
      femoral fractures) were treated with a modified Grosse-Kempf slotted locking nail
      (cephalomedullary nail), wherein two screws were inserted in the hip. Four types
      of complex, multifocal femoral fractures were represented in the series. Eleven
      of the femoral shaft fractures were secondary to a previous, internally fixed,
      not yet united hip fracture (type I). Ten comminuted peritrochanteric fractures
      occurred in normal bone (type II). Three similar fractures were pathologic
      because of metastasis. Two patients had an ipsilateral fracture of the femoral
      shaft and the trochanteric area (type III), and one of the shaft and the femoral
      neck (type IV). Locking was made static in 24 cases. Additional cerclage wiring
      was used in three type II fractures. Five complications were as follows: one
      cutting out of a screw in the femoral head, two fractures of the nail, one deep
      venous thrombosis, and one wound hematoma. Reoperations were two salvage
      operations using a new nail and one evacuation of hematoma. One patient with
      multiple injuries and four elderly patients died within 2 months. Eighteen
      patients with fractures in normal bone were followed for a median of 20 (6 to 37)
      months. All fractures united. Two nails were removed. The end result was
      excellent in ten patients, good in seven, and fair in one (2-cm shortening and 20
      degree external rotation). We conclude that a locked intramedullary construct
      with locking screws in femoral neck and distal femur controls a complex fracture
      situation well.

PMID- 8576970
TI  - Copper, selenium, and zinc status and balances after major trauma.
AB  - To investigate the trace elements (TE) losses and status after trauma, 11
      severely injured patients (Injury Severity Score: 29 +/- 6), admitted to the ICU
      were studied from the day of injury (D0) until D25. Balance studies were started
      within 24 hours after injury, until D7. Serum and urine samples were collected
      from D1 to D7, then on D10, 15, 20, and 25. Intravenous TE supplementation was
      initiated upon admission. SERUM: Selenium (Se) and zinc (Zn) levels were
      decreased until D7 and were normal thereafter. LOSSES: TE urinary excretions were
      higher than reference ranges until D20 in all patients. Fluid losses through
      drains contained large amounts of TE. BALANCES: Balances were slightly positive
      for copper (Cu) and Zn, and negative for Se from D5 to D7 despite supplements. Cu
      status exhibited minor changes compared to those observed with the Zn and Se
      status: Serum levels were decreased and losses increased. Considering the
      importance of Se and Zn in free radical scavenging, anabolism, and immunity,
      current recommendations for TE supplements in severely traumatized patients ought
      to be revised.

PMID- 8576971
TI  - Renal vascular responses to high and low ionized calcium: influence of
      norepinephrine in the isolated perfused rat kidney.
AB  - OBJECTIVE AND DESIGN: The aim of this study was to examine the influence of
      norepinephrine (NE) on renal vascular responses to high (1.88 mmol/L) and low
      (0.56 mmol/L) perfusate-ionized calcium ([Ca2+]) in the isolated perfused kidney
      of the rat. High and low [Ca2+] encompassed the clinical concentration range in
      this multiexperiment, randomized trial. MATERIALS AND METHODS: Rats (n = 25),
      ranging in age from 3 to 4 months, were anesthetized and the ureter and renal
      artery were cannulated. The right kidney was perfused with oxygenated, warmed
      albumin (67 g/L) containing Krebs-Henseleit buffer and placed in a thermostated
      chamber without interruption of flow. In protocol A (n = 7), steady-state high
      [Ca2+] (1.88 mmol/L) and low [Ca2+] (0.56 mmol/L) were instituted in randomized
      order in each experiment under basal conditions. In protocol B (n = 9), the same
      interventions were instituted during constant rate NE infusion. Changes in renal
      flow were measured at constant perfusion pressure (110 mm Hg), and renal vascular
      resistance (RVR) was calculated. Renal function was assessed by clearance of
      [14C]inulin and by fractional excretion of sodium. With NE-induced
      preconstriction, the increase in RVR observed during high [Ca2+] was +17.8 +/-
      1.8% of control, and the decrease in RVR observed during low [Ca2+] was -35.9 +/-
      8.2% of control. Both values were greater by a factor of 2 than corresponding
      results obtained under basal conditions (7 +/- 2.1% vs. -13.5 +/- 4.1% of
      control, respectively, p < 0.05). Whereas the decrease in glomerular filtration
      rate with high [Ca2+] was not significantly influenced by NE pretreatment (-9 +/-
      1.8% of control with high [Ca2+] in combination with NE vs. 4.1 +/- 0.7% of
      control under basal conditions), the increase in glomerular filtration rate with
      low [Ca2+] was significantly greater in the presence of NE (12 +/- 0.7 vs. 102 +/
      8.5% of control, p < 0.01). CONCLUSIONS: Whereas under basal conditions renal
      vascular effects of high and low [Ca2+] (varied within the clinical concentration
      range) are small, the changes recorded with the same interventions after NE
      pretreatment are increased by a factor of > 2. Hypercalcemia-induced renovascular
      constriction and decreased function are unfavorable, especially in patients who
      are at risk for renal dysfunction from other causes.

PMID- 8576972
TI  - Intra-abdominal injury with handlebar hernia: case report and literature review.

PMID- 8576973
TI  - Delayed rupture of the abdominal aorta in a child after a suspected handlebar
      injury.
AB  - Blunt abdominal trauma resulting in a laceration of the abdominal aorta is
      extremely rare. Only one previous example of this injury has been reported in a
      child. We present the clinical course and surgical management of blunt disruption
      of the infrarenal aorta in a 13-year-old boy with a subsequent delayed rupture of
      a third aortic laceration. This is the youngest patient to die from this type of
      injury after blunt abdominal trauma.

PMID- 8576974
TI  - Traumatic lumbar hernia: a seat belt injury.
AB  - A motor vehicle passenger sustained an acute traumatic lumbar hernia caused by an
      improperly positioned seat belt. Diagnosis was confirmed on computed tomographic
      scan, and the defect repaired primarily.

PMID- 8576975
TI  - Pseudoaneurysm of the proper hepatic artery with duodenal fistula appearing as a
      late complication of blunt abdominal trauma.
AB  - Posttraumatic pseudoaneurysms of the hepatic artery are rare and usually occur as
      a complication of open abdominal trauma. Even less common is the coexisting
      presence of enteric fistulization. We report a patient with upper
      gastrointestinal hemorrhage occurring 3 years after blunt abdominal trauma
      resulting from a pseudoaneurysm of the proper hepatic artery with duodenal
      fistulization. The patient was treated successfully by ligation of the proper
      hepatic artery and closure of the duodenal opening.

PMID- 8576976
TI  - Acute aortic dissection after blunt chest trauma.
AB  - Medial dissection of the aorta after blunt trauma is a rare occurrence. We report
      the case of a 79-year-old woman injured in a motor vehicle crash who suffered an
      acute DeBakey type I aortic dissection.

PMID- 8576977
TI  - Combined repair of a traumatic rupture of the aorta and anterior stabilization of
      a thoracic spine fracture: a case report.
AB  - The combination of traumatic aortic rupture and spine fracture is rare. We
      describe the treatment of both injuries in a one-stage procedure with good
      results in a 47-year-old woman.

PMID- 8576978
TI  - Vertebrobasilar thrombosis associated with nonpenetrating cervical spine trauma.
AB  - Vertebral artery injuries associated with blunt trauma to the cervical spine are
      rare. Five cases of vertebrobasilar complications after blunt trauma to the
      cervical spine are reported. Four were involved in motor vehicle accidents, and
      one suffered a diving injury. All of these patients had documented cervical spine
      fractures. For two patients, the diagnosis of vertebral artery thrombosis was
      made on the basis of magnetic resonance angiography (MRA), and for the remaining
      three, cervical four-vessel arteriograms (CFVAs), were used. All the patients had
      occlusion of flow in either the vertebral artery or in the vertebrobasilar
      circulation. The patients presented with acute, non-specific changes in
      neurological status. Two patients had infarctions in the vertebrobasilar
      tertiary, one had an infarction in the middle cerebral artery territory, and two
      did not show evidence of cerebral infarction. Three of the patients were treated
      with anticoagulants. Of these, two showed a stabilization of their neurological
      status, and one died. The four surviving patients improved with early physical
      and occupational therapy. Although CFVA remains the "gold standard" for
      diagnosing these injuries, newer modalities, such as MRA, may be useful adjuncts.
      Early stabilization of the cervical spine injury and anticoagulation are
      beneficial.

PMID- 8576979
TI  - Vertical fracture of the central sacral canal: plane and simple.
AB  - A case is reported of a sagittal fracture of the sacrum associated with diastasis
      of the symphysis pubis. The patient suffered no lasting neurologic injury. A
      literature review suggests that these vertical fractures may carry a better
      prognosis than other sacral fractures that involve the central canal.

PMID- 8576980
TI  - Purtscher's retinopathy associated with mandibular fracture: a case report.
AB  - This report describes irreversible deterioration of vision after Purtscher's
      retinopathy associated with a fractured mandible. This rare phenomenon will be
      discussed, its literature will be reviewed, and its possible etiology will be
      suggested.

PMID- 8576981
TI  - Eye injuries in women's lacrosse: strict rule enforcement and mandatory eyewear
      required.
AB  - OBJECTIVE: To inform practitioners of the risk of ocular injury in women's
      lacrosse and to advocate the mandatory use of protective eyewear. DESIGN,
      MATERIALS AND METHODS: Athletes reported retrospectively, via a questionnaire, on
      the nature and circumstances leading to their injuries. MEASUREMENTS AND MAIN
      RESULTS: Four case reports of injury to ocular and adjacent nasal structures are
      presented. None of the athletes was wearing protective equipment at the time that
      her injuries were incurred. CONCLUSIONS: Mandatory eye protection should be
      introduced into the game of women's field lacrosse. Eyewear may have prevented
      the injuries reported in this article.

PMID- 8576982
TI  - Scapulothoracic dissociation: a devastating injury.
AB  - Scapulothoracic dissociation, although rare, causes significant morbidity and
      mortality by completely disrupting the attachments of the scapula to the axial
      skeleton with the skin remaining intact. The defining constellation of injuries
      is subclavian or axillary vascular disruption, lateral displacement of the
      scapula, separation of the clavicular articulations with or without fracture of
      the clavicle, and cervical nerve root avulsion or brachial plexus injury.
      Orthopedic stabilization, vascular repair, and brachial plexus exploration are
      mandatory. Above elbow amputation, either primarily or within 24 hours, is
      recommended for the flail extremity.

PMID- 8576983
TI  - Ureteral entrapment in the sacroiliac joint in pelvic trauma.
AB  - We describe a case of unilateral entrapment of the ureter in the sacroiliac joint
      of a patient who sustained blunt abdominal trauma resulting in fractures of the
      public rami and sacroiliac joint and multiple bladder perforations. The
      entrapment was discovered intraoperatively and released by external traction and
      reduction of the pelvic fractures. No ureteric damage was observed, and
      reimplantation was not necessary. The importance of evaluating the upper tracts
      for potential injury in patients with fractures of the bony pelvis and
      concomitant bladder rupture is emphasized.

PMID- 8576984
TI  - Vasodilator provocation of occult urinary tract hemorrhage.
AB  - This case demonstrates the use of vasodilators to reactivate an intermittent
      urinary tract hemorrhage. The site of bleeding was demonstrated and treated with
      subselective embolization.

PMID- 8576985
TI  - Acute scrotal swelling after blunt thoracoabdominal trauma.

PMID- 8576986
TI  - Delayed presentation of a penetrating biliary tract injury in a child.
AB  - An 8-year-old child presented with obstruction of the common hepatic duct from a
      9-mm bullet that had entered her liver 22 months earlier. Evaluation revealed
      migration of the bullet with complete obstruction of the common hepatic duct.
      Surgical removal and reconstruction with hepaticojejunostomy has provided long
      term drainage.

PMID- 8576987
TI  - Gastric rupture after the Heimlich maneuver.
AB  - Since 1975, the Heimlich maneuver has been widely applied to relieve upper airway
      obstruction caused by aspirated material. Life-threatening complications have
      been documented following this simple procedure. We report two cases of gastric
      rupture after use of the Heimlich maneuver. Both patients experienced pulmonary
      and abdominal symptoms. The diagnosis was confirmed in each case by the
      demonstration of free intraperitoneal air on an upright chest roentgenogram. Full
      thickness gastric rupture along the lesser curvature of the stomach was repaired
      in both patients; one patient died. Abdominal pain or persistent abdominal
      distention despite nasogastric suction after the Heimlich maneuver should prompt
      evaluation for possible gastric rupture.

PMID- 8576988
TI  - Unusual cause of hypotension associated with penetrating trauma.
AB  - In a hypotensive patient who has sustained a penetrating injury, the hypotension
      is usually due to acute blood loss. We present a patient who was stabbed in the
      subxiphoid region found to have an unusual cause of hypotension.

PMID- 8576989
TI  - Major vascular injury from high-pressure water jet.
AB  - High-pressure water jets are used in industry as a cleaning and cutting tool.
      Penetrating injuries by these devices can produce minimal external evidence of
      extensive internal damage. We report a literature review and the case of a limb
      threatening injury to the lower extremity caused by such a device.

PMID- 8576990
TI  - Management of BB shot wounds to the heart.
AB  - OBJECTIVE: The aim of this study was to review our experience with BB shot
      injuries to the heart. DESIGN: This is a retrospective chart review. MATERIALS
      AND METHODS: Three patients were found to have BB injuries to the heart. All
      patients were stable upon presentation. Echocardiography localized the BB pellets
      to the muscular septum. MEASUREMENTS AND MAIN RESULTS: All patients were treated
      with nonoperative therapy. There was not mortality. One patient developed an
      interventricular conduction delay that resolved before discharge. CONCLUSIONS:
      Nonoperative management of stable patients who present with BB wounds to the
      heart is safe and effective if the BB is intramuscular. An echocardiogram should
      be used to localize the pellets and evaluate the pericardium.

PMID- 8576991
TI  - Treatment of femur fracture with associated vascular injury.
AB  - OBJECTIVE: The aim of this study was to determine (1) if internal fixation was
      associated with a high amputation rate in patients with femur fracture and
      vascular injury; and (2) if patients who underwent internal fixation before
      vascular repair had a higher amputation rate. DESIGN: This is a retrospective
      analysis. MATERIALS AND METHODS: Twenty-six patients requiring femoral
      stabilization with injury to the superficial femoral artery, popliteal artery, or
      common femoral vein were studied. The Injury Severity Score and the Mangled
      Extremity Severity Score were calculated for each. Nineteen patients underwent
      internal fixation. Ten patients had internal fixation before vascular repair.
      RESULTS: Sixteen of 19 patients treated with internal fixation had limb salvage.
      Nine of 10 patients who had internal fixation before vascular repair had limb
      salvage. Poor outcomes (gangrene, amputation, or death) were associated with a
      Mangled Extremity Severity Score > or = 6 (p = 0.005). CONCLUSIONS: In these
      patients, poor outcome is associated with severe leg injury, (with a Mangled
      Extremity Severity Score of > or = 6). Internal fixation can be safely used, and
      skeletal stabilization can be safely performed before vascular repair. If
      ischemic time is prolonged, vascular shunts should be used until skeletal
      stabilization is completed.

PMID- 8576992
TI  - Effects of a subtherapeutic dose of polymyxin B on gut origin endotoxin/bacterial
      translocation.

PMID- 8576993
TI  - Salvage of superficial palmar avulsion.
AB  - Avulsion injuries of the hand caused by moving rollers usually create a distally
      or, less commonly, a laterally based skin flap. Progressive necrosis in the
      distant part of the flap usually occurs because of arterial insufficiency and
      venous stasis over the next 2 to 3 weeks. From 1991 to 1994, we applied the
      concept of the "arterialized venous flap" to salvage the palmar tissue by
      revascularizing the superficial palmar venous network with an arterial
      anastomosis in eight patients. Six of the flaps survived completely and two had a
      small strip of marginal necrosis which healed secondarily. When compared with
      conventional methods, this method can remarkably improve the circulation of the
      flap and provide a better cosmetic and functional result for the highly
      specialized palmar tissue.

PMID- 8576994
TI  - Beaten to death: why do they die?
AB  - The remains of 53 men that had been beaten to death were examined. Six (11.3%)
      died of either blood aspiration or intracranial hemorrhage; 15 of the cases
      (28.3%) succumbed to hypovolemic shock, and 32 of the cases (60.4%) died of fat
      embolism syndrome (FES). Fractures of long bones were found only in four victims.
      Fatal FES produced by the mechanical disintegration of adipose tissue that
      migrates into the bloodstream seems to be a common phenomenon in the fatalities
      examined in this study. No correlation, however, was found between the presence
      of long bone fractures and the severity of FES, and no bone marrow emboli were
      detected on histologic examination of target organs. Scattered subcutaneous
      hematomata were present in all of the victims, although the volume of
      extravasated blood could not be calculated from the total surface area of the
      bruises. Contusions limited to the limbs have the potential of masking fatal
      volumes of extravasated blood that suffuse the musculature mass. Hypovolemic and
      neurogenic shock, as well as systemic effects of crush injury, should be
      considered contributing factors to death from FES. These findings contradict the
      previously published postulate that victims of blunt force trauma succumb
      primarily to massive hemorrhages.

PMID- 8576995
TI  - Status of nonoperative management of blunt hepatic injuries in 1995: a
      multicenter experience with 404 patients.
AB  - INTRODUCTION: Nonoperative management is presently considered the treatment
      modality of choice in over 50% of adult patients sustaining blunt hepatic trauma
      who meet inclusion criteria. A multicenter study was retrospectively undertaken
      to assess whether the combined experiences at level I trauma centers could
      validate the currently reported high success rate, low morbidity, and virtually
      nonexistent mortality associated with this approach. Thirteen level I trauma
      centers accrued 404 adult patients sustaining blunt hepatic injuries managed
      nonoperatively over the last 5 years. Seventy-two percent of the injuries
      resulted from motor vehicle crashes. The mean injury severity score for the
      entire group was 20.2 (range, 4-75), and the American Association for the Surgery
      of Trauma-computerized axial tomography scan grading was as follows: grade I, 19%
      (n = 76); grade II, 31% (n = 124); grade III, 36% (n = 146); grade IV, 10% (n =
      42); and grade V, 4% (n = 16). There were 27 deaths (7%) in the series, with 59%
      directly related to head trauma. Only two deaths (0.4%) could be attributed to
      hepatic injury. Twenty-one (5%) complications were documented, with the most
      common being hemorrhage, occurring in 14 (3.5%). Only 3 (0.7%) of these 14
      patients required surgical intervention, 6 were treated by transfusions alone
      (0.5 to 5 U), 4 underwent angio-embolization, and 1 was further observed. Other
      complications included 2 bilomas and 3 perihepatic abscesses (all drained
      percutaneously). Two small bowel injuries were initially missed (0.5%), and
      diagnosed 2 and 3 days after admission. Overall, 6 patients required operative
      intervention: 3 for hemorrhage, 2 for missed enteric injuries, and 1 for
      persistent sepsis after unsuccessful percutaneous drainage. Average length of
      stay was 13 days. Nonoperative management of blunt hepatic injuries is clearly
      the treatment modality of choice in hemodynamically stable patients, irrespective
      of grade of injury or degree of hemoperitoneum. Current data would suggest that
      50 to 80% (47% in this series) of all adult patients with blunt hepatic injuries
      are candidates for this form of therapy. Exactly 98.5% of patients analyzed in
      this study successfully avoided operative intervention. Bleeding complications
      are infrequently encountered (3.5%) and can often be managed nonoperatively.
      Although grades IV and V injuries composed 14% of the series, they represented
      66.6% of the patients requiring operative intervention and thus merit constant re
      evaluation and close observation in critical care units. The optimal time for
      follow-up computerized axial tomography scanning seems to be within 7 to 10 days
      after injury.

PMID- 8576996
TI  - Death and dollars: the cost of dying in the surgical intensive care unit.
AB  - INTRODUCTION: The effect of resuscitation status on the use of laboratory and
      radiologic studies was analyzed in patients at the Walter Reed Army Medical
      Center's Surgical Intensive Care Unit. METHODS: A retrospective assessment of
      laboratory and radiologic charges incurred during the last 48 hours of life by 81
      patients who died in the Surgical Intensive Care Unit between 1990 and 1992 was
      performed. Data were analyzed after separation by patient's resuscitation status.
      Each patient was assigned a resuscitation category: no limitation, do not
      resuscitate (no CPR in event of arrest), or limited therapy (specific order
      limiting care or monitoring). RESULTS: There were 4,095 laboratory tests
      performed for a total charge of $191,247. Arterial blood gas testing accounted
      for over $75,000 of these charges. Resuscitation status significantly affected
      test frequency. CONCLUSIONS: During the last 48 hours of life in an intensive
      care unit, the use of laboratory tests and radiologic exams has a substantial
      effect on the cost of care and is modified by the patient's resuscitation status.

PMID- 8576997
TI  - Improved predictions from a severity characterization of trauma (ASCOT) over
      Trauma and Injury Severity Score (TRISS): results of an independent evaluation.
AB  - OBJECTIVE: In 1986, data from 25,000 major trauma outcome study patients were
      used to relate Trauma and Injury Severity Score (TRISS) values to survival
      probability. The resulting norms have been widely used. Motivated by TRISS
      limitations, A Severity Characterization of Trauma (ASCOT) was introduced in
      1990. The objective of this study was to evaluate and compare TRISS and ASCOT
      probability predictions using carefully collected and independently reviewed data
      not used in the development of those norms. DESIGN: This was a prospective data
      collection for consecutive admissions to four level I trauma centers
      participating in a major trauma outcome study. MATERIALS AND METHODS: Data from
      14,296 patients admitted to the four study sites between October 1987 through
      1989 were used. The indices were evaluated using measures of discrimination
      (disparity, sensitivity, specificity, misclassification rate, and area under the
      receiver-operating characteristic curve) and calibration [Hosmer-Lemeshow
      goodness-of-fit statistic (H-L)]. MEASUREMENTS AND MAIN RESULTS: For blunt
      injured adults, ASCOT has higher sensitivity than TRISS (69.3 vs. 64.3) and meets
      the criterion for model calibration (H-L statistic < 15.5) needed for accurate z
      and W scores. The TRISS does not meet the calibration criterion (H-L = 30.7). For
      adults with penetrating injury, ASCOT has a substantially lower H-L value than
      TRISS (20.3 vs. 138.4), but neither meets the criterion. Areas under TRISS and
      ASCOT ROC curves are not significantly different and exceed 0.91 for blunt
      injured adults and 0.95 for adults with penetrating injury. For pediatric
      patients, TRISS and ASCOT sensitivities (near 77%) and areas under receiver
      operating characteristic curves (both exceed 0.96) are comparable, and both
      models satisfy the H-L criterion. CONCLUSIONS: In this age of health care
      decisions influenced by outcome evaluations, ASCOT's more precise description of
      anatomic injury and its improved calibration with actual outcomes argue for its
      adoption as the standard method for outcome prediction.

PMID- 8576998
TI  - A comparative biomechanical evaluation of a noncontacting plate and currently
      used devices for tibial fixation.
AB  - The appearance of porous bone under fixation plates during fracture healing,
      attributed to disturbance of blood supply by the plate, has led to new plate
      designs with reduced plate to bone contact. The fixation stability afforded by
      these devices, in comparison to implants commonly used for fixation, is not well
      known. Therefore, the construct stiffnesses of osteotomized synthetic tibiae
      fixed with dynamic compression plates, external fixators, or two configurations
      of noncontact plates were compared in axial compression, bending, and torsion
      with and without cortical contact at the osteotomy site. The results of this
      study show that (1) the noncontact plated constructs achieve comparable fixation
      rigidity to constructs using dynamic compression plates or external fixators, if
      applied at a distance no greater than 5 mm from the surface of the tibia, and (2)
      the fixation rigidity of the noncontact plate decreases as the distance between
      plate and bone surface increases.

PMID- 8576999
TI  - Chronological positron emission tomographic study of severe diffuse brain injury
      in the chronic stage.
AB  - Cerebral blood flow and metabolism were investigated in five patients with severe
      diffuse brain injury in the chronic stage, using positron emission tomography
      (PET). Regional cerebral blood flow, regional oxygen extraction fraction,
      regional cerebral blood volume, regional cerebral metabolic rate for oxygen, and
      regional cerebral metabolic rate for glucose were measured bilaterally in the
      frontal, temporal, occipital, and parietal gray matter, as well as the white
      matter of the centrum semiovale. In 4 of 5 patients, a follow-up PET study was
      also performed. In three cases, below-normal regional cerebral blood flow and
      regional cerebral metabolic rate for oxygen values accompanied by above-normal
      regional oxygen extraction fraction values, as well as low metabolism, were
      demonstrated in the initial PET studies. In two of three cases, clinical
      improvements were observed, and follow-up PET data also improved. These findings
      suggest that chronological PET studies may be able to assess quantitatively
      clinical improvements in patients with diffuse brain injury.

PMID- 8577000
TI  - Civilian cases of tangential gunshot wounds to the head.
AB  - A series of 168 civilian cases of tangential gunshot wounds to the head is
      presented. Neurologic deficits on presentation were generally minimal. Computed
      tomographic (CT) scans were performed in 51% of patients, and abnormal CT
      findings were noted in 35% (18% of all patients). Major operative procedures were
      required in 9% of the patients. Serious sequelae of tangential injuries are
      described even with patients who initially have no neurologic abnormality. We
      suggest that a CT scan is warranted in all cases of tangential gunshot wounds to
      the head.

PMID- 8577001
TI  - Pediatric blunt cardiac injury: epidemiology, clinical features, and diagnosis.
      Pediatric Emergency Medicine Collaborative Research Committee: Working Group on
      Blunt Cardiac Injury.
AB  - AIM: The goal of this study was to describe the epidemiology, clinical
      presentation, diagnostic methods, and outcome in a large series of children with
      blunt cardiac injury (BCI). METHODS: A multicenter retrospective review of all
      individuals less than 18 years of age diagnosed with a BCI from 1983 to 1993 was
      conducted. Cases included all those with a discharge diagnosis of myocardial
      contusion, concussion, ventricular disruption, or unspecified BCI. RESULTS: A
      total of 184 cases of BCI were identified in 16 participating centers. The median
      age was 7.4 years, and 73% were male. Myocardial contusions accounted for 95% of
      the diagnoses. The leading mechanisms were motor vehicle crashes involving a
      pedestrian (39.7%) or passenger (31.0%). The majority (87%) had multiple system
      trauma, with a mean Injury Severity Score of 27.2 (SD +/- 14.4). Pulmonary
      contusions were present in 50.5% and rib fractures in 23.0%. The most common
      diagnostic test performed was a 12-lead electrocardiogram (EKG) (82%), followed
      by a MB band of creatine phosphokinase (CPK-MB) (69%) and echocardiogram (65%).
      All three tests were performed in 50%. In these patients, agreement among various
      diagnostic test pairs was fair (echocardiogram vs. EKG, kappa = 0.27) to poor
      (echocardiogram vs. CPK-MB, kappa = 0.07 and EKG vs. CPK-MB, kappa = 0.08). No
      hemodynamically stable patient who presented with a normal sinus rhythm
      subsequently developed a cardiac arrhythmia or cardiac failure. There were 25
      deaths (13.6%), 3 of which were caused by acute pump failure secondary to massive
      cardiac injury. The remainder died of head or abdominal injuries. Of the 159
      (86.4%) patients surviving, 8 (5% of survivors) had significant cardiac sequela,
      most commonly mitral or tricuspid insufficiency or ventricular septal defect.
      CONCLUSIONS: Pediatric BCI is usually diagnosed in the context of severe multiple
      system trauma and is less commonly an isolated event. Because of the lack of a
      standard, various diagnostic tests are used in the diagnosis of BCI, and these
      tests rarely agree. In hospitalized pediatric patients with BCI, unanticipated
      complications are rare. Significant sequela, although uncommon, do occur and
      follow-up of children with BCI should be ensured.

PMID- 8577002
TI  - Strangulation injuries in children. Part 1. Clinical analysis.
AB  - Over the past 4 years, 7.4% of deaths caused by strangulation in Peoria County,
      Ill., involved children under 18 years of age. Clinical review of a consecutive
      series of 13 children treated from 1985 through 1994 revealed an incidence of 32
      of 10,000 intensive care unit admissions with a 5.5:1 male bias. Accidental
      causes were seen in six children, with suicide or autoerotic causes prevalent in
      older children and adolescents. Five children had behavioral disorders before
      injury. The initial Glasgow Coma Scale score was 8 or below in seven children.
      Cervical roentgenograms in all patients and computed tomographic examinations
      performed in seven children were interpreted as normal. Seven children required
      ventilatory assistance, and four had pneumonia or acute lung injury. Intracranial
      pressure monitoring in three children failed to reveal sustained elevations of
      pressure. Serial changes in electroencephalograms in five patients paralleled
      improvements in their clinical examinations. Ten children were normal on follow
      up; one adolescent reported mild neurologic sequelae and one adolescent showed
      severe disability. One adolescent died 2 days after injury. Comparison of this
      series with previous reports of 26 children indicated that the extent of the
      initial injury and effectiveness of resuscitation were major determinates for
      outcome. Pulmonary complications were common, whereas the development of elevated
      intracranial pressure indicated a poor prognosis and suggested the use of
      telemetry in children, with clinical evidence of severe injury. Continued
      awareness of preventative measures for accidental strangulation in infants and
      intentional hanging in children with behavioral disorders may reduce the
      incidence of these injuries.

PMID- 8577003
TI  - Strangulation injuries in children. Part 2. Cerebrovascular hemodynamics.
AB  - The cerebrovascular hemodynamics were recorded in two children with comparable
      hypoxic-ischemic injuries after strangulation. Monitoring was initiated within 13
      hours of injury and continued for at least 38 hours. The profile included
      continuous measurements of cortical regional cerebral blood flow (rCBF) with a
      subdural thermal diffusion probe, intracranial pressure, mean arterial pressure,
      and expired CO2 tension. Data sets were obtained every 15 minutes or every 5
      minutes during epochs of hyperventilation and inotropic support. Arterial CO2 and
      oxygen content and pH and, in the second patient, cardiac output (and cardiac
      index) were determined every 3 to 6 hours. Both children showed cortical
      hyperemia with a gradual rise of rCBF during the study; neither child showed
      elevated intracranial pressure. Mean CO2 reactivities were 1.8 and 2.1 mL/100
      g/minute/mm Hg, with gradual elevations during the study. Mean cerebrovascular
      resistances were 0.7 and 0.9 mL/100 g/minute/mm Hg, respectively. Dissociative
      vasoparalysis with loss of autoregulation and preservation of CO2 reactivity was
      observed in both children. In the second child, during two periods of
      hyperventilation, an inverse steal occurred with rCBF indirectly related to
      expired CO2 tension; the rCBF was not related to changes in cardiac output or
      cardiac index. Neurologic outcome was not related to mean levels of rCBF, CPP,
      and CO2 reactivity, or clinical dissociative vasoparalysis. Lower initial and
      mean values of rCBF and an inverse steal after hyperventilation were associated
      with a poor outcome in the second patient.

PMID- 8577004
TI  - Major trauma in young and old: what is the difference?
AB  - OBJECTIVE: To evaluate the differences in mortality and long-term outcome between
      young and elderly patients with multiple injuries. DESIGN: Retrospective and
      descriptive. MATERIALS AND METHODS: Over a 5-year period (from January 1985 to
      January 1990) all the consecutive young (20 to 29 years, n = 167) and elderly (>
      or = 60 years, n = 121) patients with an Abbreviated Injury Scale score/Injury
      Severity Score of > or = 16 treated at the University Hospital Groningen (the
      Netherlands) were reviewed. Age, sex, mechanisms of injury, Abbreviated Injury
      Scale score, Injury Severity Score, mortality, duration of artificial
      ventilation, hospitalization, and intensive care treatment and discharge
      destination were analyzed. Long-term outcome was determined using the Glasgow
      Outcome Scale. MEASUREMENTS AND MAIN RESULTS: Motorized vehicles were the leading
      cause of injury in both groups. Mortality in the young was lower than in the
      elderly (19.6% versus 38.8%); all elderly with an Injury Severity Score of > or =
      50 died. Nearly all deaths in young and elderly were caused by severe brain
      injuries (83.8% versus 74.4%). Deaths related to multiple organ failure were not
      observed in the young and were rare in the elderly. The surviving young and
      elderly could be discharged home in equal percentages and their functional
      outcome 2 years after injury did not differ essentially. CONCLUSION: We did not
      find any valid argument to treat severely injured elderly patients any
      differently from their younger counterparts, which implies that the increased
      trauma care cost is also justified for severely injured elderly.

PMID- 8577005
TI  - Pulmonary complications in inhalation injuries with associated cutaneous burn.
AB  - This retrospective study of 100 consecutive patients with inhalation injury
      documents that adult respiratory distress syndrome (ARDS) and pneumonia are
      common complications. Pulmonary complications cause or directly contribute to
      death in 77% of patients with combined inhalation and cutaneous burn injury.
      Additionally, the high fluid requirements of these patients worsens their
      pulmonary injury and is associated with adverse outcome. Independent factors
      predictive of death include ARDS and expected fluid requirements as well as age
      and percentage of total body surface area burned. An abnormal chest roentgenogram
      in the first 48 hours after injury is also associated with death. The development
      of ARDS is predicted by the actual volume of fluid resuscitation, despite normal
      pulmonary wedge pressure or normal central venous pressure reflecting increased
      microvascular permeability. These findings indicate a need for reevaluation of
      fluid resuscitation of patients with inhalation injury.

PMID- 8577006
TI  - Influence of pentoxifylline and albifylline on liver microcirculation and
      leukocyte adhesion after hemorrhagic shock in the rat.
AB  - The aim of this study was to evaluate the effects of two xanthine derivates,
      pentoxifylline (PTX) and its more metabolically stable analogue, albifylline (HWA
      138), on hepatic sinusoidal perfusion and leukocyte endothelial interactions in
      the liver after hemorrhagic shock. Sprague-Dawley rats (n = 8 per group) were
      exposed to hemorrhagic shock at 40 mm Hg for 60 minutes and subsequently
      resuscitated with 60% of shed blood and lactated Ringer's solution before
      intravital microscopy of the liver 3 hours after resuscitation. Using
      fluorescence markers, quantitative evaluations of red blood cell (RBC) and white
      blood cell (WBC) velocities and WBC endothelium interactions were performed.
      Animals were chosen randomly and blindly to receive either PTX or HWA 138 in a
      dosage of 25 mg/kg body weight 1 minute before resuscitation, or they received
      placebo. This was followed by a further infusion of 25 mg/kg body weight during
      the 3-hour resuscitation period. Although systemic parameters were comparable in
      all groups, both xanthine derivates enhanced the reduced velocity of RBCs and
      WBCs of the placebo group. Pathological values of WBC endothelium adhesion in the
      placebo group (adhesion index: 126.7 +/- 19.5 s/100 WBCs, mean +/- SE) was
      significantly reduced by PTX (64.4 +/- 10.5, p < 0.05) and HWA 138 (71.9 +/-
      10.7, p < 0.05). The results indicate a significant reduction of shock-induced
      leukocyte adhesions to the sinusoidal endothelium in the liver. In addition, both
      xanthine derivates led to improved microvascular blood flow in the liver. Thus,
      PTX and HWA 138 reveal multiple positive effects on early shock-induced
      alterations in the liver, supporting earlier studies which indicated their
      potential application in shock therapy.

PMID- 8577007
TI  - Impact of enteral feeding of a glutamine-supplemented formula on the
      hypoaminoacidemic response in trauma patients.
AB  - Plasma amino acid concentrations were measured during fasting and after 3 days of
      enteral feeding in 16 trauma patients on a glutamine-supplemented diet and 14
      patients on an isonitrogenous control diet. During fasting, total amino acids,
      including glutamine, were depressed by 50% and this was attributed to a reduction
      in both essential and nonessential amino acids. The essential amino acid
      concentrations increased in both groups after feeding. The nonessential amino
      acid concentrations also increased in the control group but not in the glutamine
      group during feeding. Repletion of the glutamine extracellular pool was not
      evident after an average intake of 27.1 g per day of glutamine for 3 days.
      Nitrogen balance was similar for the two groups during feeding. We conclude that
      in this study, enteral glutamine did not increase the glutamine plasma
      concentration. In addition, both formulas improved the hypoaminoacidemia of
      essential amino acids but only the control diet improved the nonessential amino
      acids plasma concentration.

PMID- 8577008
TI  - The effect on energy and nitrogen metabolism by continuous, bolus, or sequential
      infusion of a defined total parenteral nutrition formulation in patients after
      major surgical procedures.
AB  - BACKGROUND: The role of IV infusion kinetics to explain nutrition efficiency was
      investigated in patients after major surgical procedures. METHODS: IV nutrition
      was provided as three different infusion kinetic regimens in a randomized
      fashion. All patients received nonprotein calories (100% of predicted
      preoperative REE, 60% D-glucose, 40% fat) and amino acid nitrogen (0.2 g N/d).
      Group A: Nutrition was provided by sequential infusion with combined fat and
      amino acids during daytime and glucose alone during nighttime ("sequential
      infusion"). Group B: Patients received 24-hour combined infusion with fat, amino
      acids, and glucose (all in one mixture) ("continuous infusion"). Group C:
      Nutrition was provided by bolus infusions during 1 hour followed by 2 hours
      without any infusion ("bolus infusion"). RESULTS: The daily energy balance was
      negative in all groups (-318 +/- 25 kcal/d, sequential infusion; -368 +/- 25
      kcal/d continuous infusion; -292 +/- 20 kcal/d, bolus infusion). Significantly
      different excretion patterns of nitrogen in urine occurred among the groups
      despite an almost identical provision of nitrogen. Continuously infused patients
      retained nitrogen significantly better (-0.2 +/- 0.6 g/d) compared with
      sequentially (-3.4 +/- 1.0 g/d) and bolus-infused patients (-2.8 +/- 0.3 g/d) (p
      < .01), whereas their cumulative urinary glucose excretion was significantly
      larger. Continuously infused patients were in cumulative nitrogen balance during
      the entire postoperative period, whereas the other groups were in a significantly
      negative nitrogen balance. Urinary 3-methylhistidine excretion was similar in all
      groups. CONCLUSIONS: The breakdown of muscle proteins was not sensitive to
      alterations in nutrient and substrate supply. Thus improved nitrogen retention
      reflected entirely improved synthesis. "All-in-one" IV nutrition with prolonged
      infusion periods is at present the most favorable regimen considering both the
      nutritional efficiency and its metabolic load on the organism after major
      surgery.

PMID- 8577009
TI  - Nutrition support affects the distribution and organ uptake of cachectin/tumor
      necrosis factor in rats.
AB  - BACKGROUND: We have previously observed a potentiation of the metabolic response
      to cachectin/tumor necrosis factor (TNF) by total parenteral nutrition (TPN) but
      not in anorexic orally fed animals. We hypothesized that nutritional status might
      affect TNF clearance kinetics. METHODS: We compared the clearance of a bolus of
      labeled TNF in TPN-fed animals given sufficient nutrients to grow called weight
      gaining rats (WGR) with those given 50% of the WGR called weight-losing rats
      (WLR) and with orally fed rats (OFR). Data were analyzed using a two-compartment
      open system model and by linear systems analysis. RESULTS: The data from both
      types of analysis indicator that although metabolic clearance was similar, WGR
      had a slower fractional TNF clearance rate (FCR) as well as a larger volume of
      distribution than WLR or OFR. Further analysis showed that an increased
      proportion of the total mass of TNF resided in a plasma-associated compartment in
      WGR compared with WLR and OFR. In addition, WGR had reduced uptake of labeled TNF
      by the kidney. CONCLUSION: The data suggest that nutrition support influences
      either the distribution of TNF or the FCR, resulting in a greater retention in
      the plasma-associated compartment with intact absolute removal rates. This study
      has important implications concerning the type of nutrition support provided to
      the critically ill patient because our data suggest that clinical states with
      increased circulating TNF levels may be adversely affected by currently available
      nutritional practices.

PMID- 8577010
TI  - The effect of selenium supplementation on skeletal and cardiac muscle in selenium
      depleted patients.
AB  - BACKGROUND: The purpose of the present study was to evaluate the effect of sodium
      selenite on skeletal and cardiac muscular function in patients with severe Se
      deficiency. METHODS: Skeletal and cardiac muscular function was investigated in
      10 selenium depleted patients on long-term home parenteral nutrition because of
      short bowel syndrome. The following examinations were applied: Skeletal muscle
      biopsy, muscular force test (Kin-Com dynamometer test), electromyography (EMG)
      and radionuclide ventriculography. The patients were blindly randomized to
      intravenous supplementation with selenium 200 micrograms 5 to 7 times per week or
      placebo for 4 months. Hereafter the examinations were repeated. The patients
      randomized to placebo received selenium in an open study for a further 4 months
      and hereafter their skeletal and cardiac function was reevaluated. RESULTS:
      Plasma selenium increased to normal levels from median .21 mumol/l (range 0-.69)
      to 1.25 mumol/l (range .9-2.27) following selenium repletion. The muscle biopsies
      showed only minor abnormalities. The only change after selenium supplementation
      was a small but statistically significant increase of the mean diameter of fiber
      type 1. The muscle strength of the quadriceps muscle was unchanged after selenium
      substitution. EMG did not reveal signs of myopathy. The cardiac function was
      normal and remained unchanged. CONCLUSION: Despite severe selenium depletion ten
      patients on long term home parenteral nutrition had normal cardiac function, and
      no clinically significant signs of skeletal myopathy. The only change after
      selenium supplementation was a small but statistically significant increase of
      the mean diameter of muscle fiber type 1.

PMID- 8577011
TI  - How effective is enteral nutrition in inducing clinical remission in active
      Crohn's disease? A meta-analysis of the randomized clinical trials.
AB  - BACKGROUND: The purpose of the study was to evaluate, using meta-analysis
      techniques, whether enteral nutrition is effective in inducing clinical remission
      in active Crohn's disease. METHODS: Randomized trials either comparing enteral
      nutrition with steroids or comparing elemental (amino acid-based) with
      nonelemental diets were selected using MEDLINE (1984 to 1994), reference lists
      from published articles, reviews, and abstracts from major gastrointestinal
      meetings. Sixteen studies fulfilled the inclusion criteria (four published as
      abstracts). Crude rates for induction of remission were collected on an intention
      to-treat basis by three independent observers. Each study was given a quality
      score, based on predetermined criteria. RESULTS: The pooled odds ratio (OR) for
      all type of enteral diets compared with steroid therapy was 0.35 (95% CI, 0.23 to
      0.53). This result was similar for the best studies (by quality score) combined,
      for trials using tube feeding combined, and when noncompliant patients were
      withdrawn. Further subgroup analyses were conducted on the basis of the type of
      diet administered. Peptide-based diets were significantly inferior to steroids
      (pooled OR, 0.32; CI, 0.20 to 0.52). There was a trend to lower remission rate
      after elemental diets than after steroids (pooled OR, 0.44; CI 0.17 to 1.12). On
      the other hand, pooled OR for whole protein-based diets compared with elemental
      diets was 1.28 (CI, 0.40 to 4.02). CONCLUSIONS: Data available to date show that
      steroids are better than enteral nutrition to induce remission in active Crohn's
      disease. These results are more evident when peptide-based diets are
      administered, but they are not conclusive when either elemental or whole protein
      based diets are used.

PMID- 8577012
TI  - Practical aspects of enteral nutrition in the management of Crohn's disease.
AB  - BACKGROUND: Enteral nutrition regimens achieve remission from active Crohn's
      disease at rates comparable to steroids and total parenteral nutrition. Despite
      their increasing use there has to date been no assessment of patient tolerance or
      practical difficulties involved. METHODS: We investigated 147 treatments with
      elemental diet in 89 patients and followed this with an anonymous questionnaire.
      RESULTS: Sip feeding was successfully introduced in 85% with nasogastric feeding
      being necessary in 22 (15%). Nausea and postural hypotension were common in the
      first week of treatment but vomiting was only seen in three patients who were
      sensitive to the formula used. Two patients each had caffeine withdrawal symptoms
      and hypoglycemia and a further four had food-related night terrors. Our
      experience suggests that caution is necessary if this treatment is used in
      elderly subjects. Although the diets are perceived as being unpalatable, only six
      patients found taste to be a problem after the first week of treatment. The main
      problem with long-term treatment was the large daily volume requirement, which
      was overcome by increasing the concentration of the feed. Eighty percent of
      patients responded to the questionnaire, and 65% stated that they would opt for
      treatment with elemental diet again in the case of a further relapse.
      CONCLUSIONS: Elemental diet seems to be an acceptable and well-tolerated form of
      treatment in Crohn's disease.

PMID- 8577013
TI  - Effects of administration of different intravenous lipid emulsions on plasma LP-X
      concentrations in the rat.
AB  - BACKGROUND: Prolonged parenteral nutrition with lipid emulsions is essential to
      provide sufficient energy supply and to avoid essential fatty acid deficiency in
      preterm infants. However, chronic administration of lipid emulsions may lead to
      the development of pathological plasma lipid and LP-X concentrations. The aim of
      this study was to evaluate the relative importance of the phospholipid
      triglyceride (PL-TG) ratio and the source of phospholipid in lipid emulsions,
      with respect to plasma lipid and LP-X levels. METHODS: Rats were infused for 9
      days with IV lipid emulsion containing 10% (IL-10) or 20% (IL-20) egg lecithin or
      Lipofundin containing 20% soya lecithin (LF), with PL-TG ratios of .12, .06, and
      0.75, respectively. RESULTS: LF significantly increased plasma triglyceride
      concentration (p < .01), whereas the rise in cholesterol levels observed with all
      emulsions was primarily caused by the increase in low-density lipoprotein
      cholesterol concentrations. The plasma phospholipid concentration was increased
      most by IL-10 (p < .005). There was a strong correlation between the PL-TG ratio
      of emulsions and the developing plasma phospholipid and LP-X concentrations (r2 =
      .91 and .96, respectively), despite the different origin of phospholipids in the
      emulsions, suggesting that it is the PL-TG ratio, rather than the source of
      phospholipids in lipid emulsions that primarily influences developing plasma
      lipid and LP-X concentrations. CONCLUSION: These results indicate that the
      administration of lipid emulsions with lower PL-TG ratios should be considered,
      to avoid the development of pathological plasma lipoprotein concentrations.

PMID- 8577014
TI  - Diminished protection against copper-induced lipid peroxidation by cord blood
      plasma of preterm and term infants.
AB  - BACKGROUND: Blood plasma of neonates is less able to inhibit iron induced lipid
      peroxidation than plasma of older patients. Copper, also a powerful pro-oxidant,
      may accumulate in ill babies because of excess intake or decreased excretion. We
      assessed in vitro the ability of plasma of neonates to inhibit copper induced
      peroxidation damage. METHODS: Peroxidation of phospholipid liposomes, induced by
      CuCl2, was measured with a thiobarbituric acid assay. The ability of plasma from
      venous blood of adults and cord blood of babies to inhibit peroxidation was
      compared. The levels of the copper binding plasma proteins, albumin and
      ceruloplasmin, were also measured. RESULTS: Protection against copper induced
      lipid peroxidation was much higher with adult plasma compared to neonatal plasma.
      Despite their lower albumin and ceruloplasma levels the protection by the plasma
      of preterm babies was higher than that of the term babies. CONCLUSIONS: At birth,
      babies have a limited ability to inhibit copper induced oxidative damage in
      vitro. Postnatal studies are needing to assess the influence of maturation and
      nutrition on these findings and their relevance in diseases induced by reactive
      oxygen species.

PMID- 8577015
TI  - Morphometric changes in microvasculature in rat myocardium during malnutrition.
AB  - BACKGROUND: Because the interrelationship between the parenchymal cell population
      and the microvasculature is critical in normal organ function, the effects of
      starvation on rat myocardium were studied morphometrically with respect to the
      microvasculature. METHODS: Morphometric analytical studies were performed on
      myocardium of adult, female Wistar rats (groups of 5-7 rats) on fasting days 0,
      1, 2, 4, 6, 8 and 10. Since cardiac muscle is a tissue with a high level of
      anisotropy, methods based on the concept of vertical planes were used to describe
      quantitative alterations in the rat myocardium both at the cellular and
      ultrastructural level. RESULTS: Morphometric analysis of electromicrographs of
      myocardium showed an increase in capillary density together with a decrease in
      capillary lumen cross-sectional area during starvation (p < .05). There was no
      significant change in volume fraction of the capillaries but surface density of
      the myocytes increased significantly (p < .01) and the diffusion distance for
      oxygen from the capillary lumen to the mitochondrion decreased (p < .01).
      CONCLUSIONS: Malnutrition alters the interrelationship between parenchyma and
      vascularization in the heart. This leads to a significant decrease of the
      diffusion distance for metabolites. This decrease of diffusion distance may
      improve cellular energy supply and offers a relative protection of the metabolism
      in the malnourished myocyte.

PMID- 8577016
TI  - Structured triglycerides were well tolerated and induced increased whole body fat
      oxidation compared with long-chain triglycerides in postoperative patients.
AB  - BACKGROUND: It has been proposed, on the basis of animal experiments, that medium
      chain triglycerides (MCT) may exert more favorable effects on whole body
      metabolism of injured animals than long-chain triglycerides (LCT). Therefore, the
      present study was designed to evaluate whether structured triglycerides are
      associated with increased whole body fat oxidation without promotion of
      ketogenesis in postoperative patients. METHODS: A structured lipid emulsion
      (73403 Pharmacia, Sweden) containing medium- and long-chain fatty acids,
      esterified randomly to glycerol in a triglyceride structure, was used. Whole body
      fat oxidation was determined by indirect calorimetry in the postoperative period.
      Patients were randomized to receive structured lipids 1 day followed by LCT
      (Intralipid, Pharmacia) the next day or vice versa during 6 postoperative days.
      In part 1 of the study patients received fat at 1.0 g/kg per day in the presence
      of 80% of the basal requirement of nonprotein calories. In part 2 patients
      received fat at 1.5 g/kg per day in the presence of 120% of the nonprotein
      caloric requirement. Amino acids were always provided at 0.15 g N/kg per day.
      RESULTS: Structured lipids were not associated with any side effects, were
      rapidly cleared from the plasma compartment, and were rapidly oxidized without
      any significant hyperlipidemia or ketosis. Provision of structured lipids in the
      presence of excess of nonprotein calories (part 2) caused a significantly higher
      whole body fat oxidation (2.4 +/- 0.05 g/kg per day) compared with LCT provision
      (1.9 +/- 0.06 g/kg per day) (p < .0001) examined in the same patients.
      CONCLUSIONS: The results demonstrated for the first time in man that provision of
      structured triglycerides were associated with increased whole body fat oxidation
      in stressed postoperative patients, which is in line with the original metabolic
      and biochemical concept for structured triglycerides. The study provided evidence
      to support that structured lipids may represent a next generation of IV fat
      emulsions that may be clinically advantageous compared with conventional LCT
      emulsions in certain clinical conditions.

PMID- 8577017
TI  - Early nutrition support modifies immune function in patients sustaining severe
      head injury.
AB  - BACKGROUND: Immunosuppression after severe head injury has been characterized by
      a depressed CD4 (T-helper/inducer)-CD8 (T-suppressor/cytotoxic) ratio and
      decreased T-lymphocyte responsiveness. Some investigators propose that this
      immunocompromized state is the result of an injury-associated hypermetabolic
      response and inadequate nutrient delivery during the immediate postinjury
      recovery phase. Previous observations from our institution demonstrated a
      preserved CD4-CD8 ratio in severe closed-head injury (CHI) patients receiving
      early parenteral nutrition (PN). It was unclear whether early PN or other aspects
      of patient care eliminated the characteristic depression in cellular immunity.
      The purpose of this study was to further investigate the effect of early PN on
      the immune function of CHI patients. METHODS: Nine patients sustaining severe CHI
      were prospectively randomized to either early PN (n = 4) at day 1 or delayed PN
      (n = 5) at day 5. Total nutrient administration was delivered at 2 g of
      protein/kg per day and 40 nonprotein kcal/kg per day for at least the first 14
      days of hospitalization. Analysis for T-lymphocyte expression of CD4 and CD8 cell
      surface antigens and interleukin-6 was performed on days 1, 3, 7, and 14 of
      hospitalization. T-lymphocyte activation in response to stimulation by
      concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogens (PWM) was
      also assessed on these days. RESULTS: Significant increases in total CD4 cell
      counts (2048 +/- 194 to 2809 +/- 129 vs 1728 +/- 347 to 1825 +/- 563, p < .05)
      and CD4% (42.6 +/- 4.4% to 56.2 +/- 2.6% vs 36.6 +/- 6.6% to 36.6 +/- 11.3%, p <
      .05) were observed at day 14 in patients receiving early vs delayed PN. An
      improved lymphocyte response from baseline to day 14 after Con A stimulation was
      demonstrated in the early PN group (3850 +/- 1596 to 16144 +/- 5024 cpm, p <
      .05). A significant rise in the CD4-CD8 ratio over baseline to day 14 was also
      noted in the early PN group (1.43 +/- 0.17 to 2.38 +/- 0.54, p < .05).
      CONCLUSIONS: The early aggressive nutrition support of CHI patients appears to
      modify immunologic function by increasing CD4 cells, CD4-CD8 ratios, and T
      lymphocyte responsiveness to Con A.

PMID- 8577018
TI  - Effect of intragastric pH on the absorption of oral zinc acetate and zinc oxide
      in young healthy volunteers.
AB  - BACKGROUND: Zinc is an important nutrient and is necessary to maintain a
      multitude of physiologic processes. Mineral supplements that provide physiologic
      doses of zinc may be used when dietary zinc is inadequate. Zinc is also used in
      pharmacologic doses to treat zinc deficiency and diseases such as Wilson's
      disease and acrodermatitis enteropathica. Although there are several zinc salts
      available, they are not equal in solubility, which is thought to be a key factor
      in zinc absorption. Moreover, the solubility of the salts is affected by pH,
      which may vary between pH 1 and 7 under various physiologic conditions in the
      stomach. The objectives of this 2-way 4-phase crossover study were to evaluate
      the effect of high (> or = 5) and low (< or = 3) intragastric pH on the
      absorption of zinc from the acetate and oxide salt in young healthy volunteers.
      METHODS: After a 9-hour fast, 10 healthy subjects (5 males and 5 females) were
      given a single oral dose of 50 mg of elemental zinc as the acetate or the oxide
      salt and under either high or low intragastric pH conditions. In all phases, a
      Heidelberg capsule pH detector-transmitter was used to continuously monitor
      intragastric pH. During the high pH phases, single oral doses of famotidine 40 mg
      oral suspension were administered before the zinc to raise the intragastric pH
      above 5. Intragastric pH < or = 3 was maintained in the low pH phases. RESULTS:
      The mean plasma zinc area under the curve for zinc acetate at low pH (AL), zinc
      acetate at high pH (AH), zinc oxide at low pH (OL), and zinc oxide at high pH
      (OH) were 524, 378, 364, and 66 micrograms x h/dL, respectively. The highest zinc
      plasma concentrations occurred with the acetate salt at a low intragastric pH,
      while the lowest plasma concentrations occurred with the oxide salt at a high
      intragastric pH. The importance of pH to the dissolution of these salts was
      verified by in vitro tests. Twenty-four-hour urinary zinc excretion was the
      highest for the AL phase and lowest for the OH phase. CONCLUSION: This study
      indicates that intragastric pH and salt solubility-dissolution are important in
      the oral absorption of zinc. Specifically, the oxide salt is not an appropriate
      zinc salt to use in those patients with elevated intragastric pH.

PMID- 8577019
TI  - The effects of light exposure on the in vitro hepatic response to an amino acid
      vitamin solution.
AB  - BACKGROUND: Administration of parenteral nutrition (PN) that has been irradiated
      with light is associated with hepatic dysfunction in rats in vivo. Using the
      isolated perfused rat liver, we report the in vitro hepatic response to a light
      exposed amino acid-vitamin (AAV) solution, compared with a light-protected
      solution. METHODS: The amino acid-vitamin solution (3 g Aminosyn and 2.5 mL MVI
      12 added to buffer) was placed under a lamp in a beaker that was covered
      completely with foil (light-protected) or with a transparent wrap (light-exposed)
      for 24 hours before liver perfusion. Livers from adult male rats were isolated
      and perfused with buffer for 30 minutes, with the AAV solution for 60 minutes,
      and again with buffer for 30 minutes. RESULTS: Infusion with the AAV solution
      resulted in decreases in bile flow rates. Compared with light-protected groups,
      light-exposure was associated with significantly lower bile flow rates,
      significant increases in biliary concentrations of oxidized glutathione (GSSG),
      and significantly decreased biliary concentrations of free amino acids, including
      the glutathione precursors glutamate and glycine. CONCLUSIONS: Perfusion of the
      isolated rat liver with an AAV solution that has been irradiated with light for
      24 hours results in a decrease in bile flow rates and an increase in biliary GSSG
      concentrations, suggesting oxidant stress. Consideration should be given to
      protecting solutions from light in the clinical setting.

PMID- 8577020
TI  - Osmolarity does not affect the gastric emptying rate of oral rehydration
      solutions.
AB  - BACKGROUND: The objective of this study was to determine the effect of either
      carbohydrate content or osmolarity on gastric emptying rate in normal healthy
      subjects. METHODS: In total 12 test drinks were ingested as a single 8 mL/kg per
      body weight bolus on an empty stomach. Six of these drinks had a different
      carbohydrate content, increasing stepwise from 45 to 90 g/L, but all with the
      same osmolarity (330 mOsm/kg). The other six drinks all contained 60 g
      carbohydrate/L but differed stepwise in osmolarity because of the use of
      maltodextrins with a difference in chain length (243 to 374 mOsm/kg). RESULTS:
      The results show a significant negative relation between carbohydrate content and
      gastric emptying in the six drinks with a uniform osmolarity but progressively
      increasing carbohydrate content. The six drinks, which had the same carbohydrate
      energy content but different osmolarities, emptied all at the same rate from the
      stomach. The delivery of carbohydrate-energy per minute from the stomach to the
      small intestine was the same for all drinks. CONCLUSIONS: From these data we
      conclude that the rate of gastric emptying of carbohydrate-containing solutions
      is triggered by the carbohydrate-energy drink content or by the delivery rate of
      carbohydrate-energy to the gut. Osmolarity in the range studied here had no
      effect.

PMID- 8577021
TI  - Does the use of hydrochloric acid damage silicone rubber central venous
      catheters?
AB  - BACKGROUND: Hydrochloric acid (HCl) is commonly used to clear obstructions in
      central venous catheters (CVC). METHODS: To determine if HCl adversely affects
      the integrity of a CVC we infused 0.1 N HCl daily into CVC in vitro. At weekly
      intervals sections of the CVC were removed and examined using scanning electron
      microscopy. RESULTS: Over 8 weeks, no damage to the CVC was visible. CONCLUSIONS:
      HCl administration poses no threat to the structural integrity of a CVC.

PMID- 8577022
TI  - Gastrointestinal surface protection and mucosa reconditioning.
AB  - BACKGROUND: There is increasing evidence that preservation of the ecology of the
      gastrointestinal tract and the surface protection system--surfactants, mucus, and
      fiber--is important for the outcome in postoperative trauma patients, patients
      after bone marrow and liver transplantation, and patients with HIV or AIDS.
      Approximately 50% of the nourishment of the small intestine and > 80% of the
      nourishment of the large intestine comes from the lumen. This is especially
      deleterious to the large intestine. Within less than a week of intestinal
      starvation--even in the presence of intense parenteral nutrition--a mucosal
      atrophy is observed, promoting translocation of potentially pathogenic
      microorganisms. Enteral nutrition is crucial to the outcome in many of these
      conditions. If however, such a nutrition is based on simple carbohydrates,
      peptides, amino acids, or fatty acids, most of the nutrition administered will be
      absorbed in the upper gastrointestinal tract. Complex fibers and proteins can be
      regarded as nutrients especially destined to the lower gastrointestinal tract.
      They are fermented by the probiotic flora, normally colonizing the colonic
      mucosa, and the necessary nutrients: short-chain fatty acids and amino acids such
      as arginine and glutamine are produced at the level of the colonic mucosa.
      Careless antibiotic treatment reduces or eliminates this flora, induces local
      mucosal starvation, and makes the patients vulnerable to opportunistic infections
      and microbial intestinal translocation. METHODS AND RESULTS: In this review the
      role of the different ingredients of the surface protection system are discussed.
      A program to recondition the intestines, particularly the colonic mucosa by
      resupply of species-specific lactobacilli, surfactants, amino acids (especially
      glutamine), and oat fiber (beta-glucans) is suggested. Extensive experience in
      animal models and early experience in a patient population are summarized and
      discussed. Oat has been chosen as a substrate for fermentation because it
      contains 100 times more of membrane lipids (surfactants) than any other food, has
      a favorable amino acid pattern (rich in glutamine), and is rich in water-soluble,
      fermentable-fiber beta-glucans. More than 1000 isolates of human-specific
      lactobacilli have been studied. Some strains, especially those of plantarum type,
      have proven effective in colonizing the colonic mucosa, suppressing the
      potentially pathogenetic flora, and may have other probiotic effects as well.
      CONCLUSION: A totally new enteral formula has been designed based on probiotic
      bacteria and fiber and aimed at colonizing the intestinal mucosa with a local
      probiotic effect and fermentation of fiber.

PMID- 8577023
TI  - Treatment of central venous catheter occlusions with ethanol and hydrochloric
      acid.
AB  - BACKGROUND: Occluded central venous lines (CVLs) is a major problem in pediatric
      patients. METHODS: To relieve obstructed catheters, infusions of ethanol (up to 3
      mL of a 70% solution) for presumed lipid occlusions and hydrochloric acid (HCl,
      0.1 N, up to 3 mL) for presumed mineral and drug precipitates were given in an
      attempt to relieve obstructed catheters. RESULTS: Patency was restored in 34 of
      39 occluded catheters over an 18-month period. CONCLUSIONS: Clearing occluded
      CVLs with ethanol and HCl is not only beneficial to the patient but also offers
      considerable cost savings compared to CVL replacement.

PMID- 8577024
TI  - TPN-induced sympathetic activation is related to diet, bacterial translocation,
      and an intravenous line.

PMID- 8577025
TI  - Growth retardation in children receiving long-term total parenteral nutrition:
      effects of ornithine alpha-ketoglutarate.

PMID- 8577026
TI  - Is the energy expenditure equation useful?

PMID- 8577027
TI  - Energy expenditure and the critically ill.

PMID- 8577028
TI  - Permanent catheters damaged by power injection of contrast media.

PMID- 8577029
TI  - Conservative management of septic parenteral nutrition catheters.

PMID- 8577030
TI  - [Lysosomal enzymes, sphingolipid activator proteins, and protective protein].
AB  - The lysosome is an intracytoplasmic acidic vacuole containing more than 60
      hydrolytic enzymes for digestion of macromolecules, such as nucleic acids,
      proteins, lipids and complex carbohydrates. Expression of lysosomal enzyme
      activities is regulated by various intracellular environmental factors. Mutation
      of a gene coding for a lysosomal enzyme results in a specific genetic disease,
      often involving the central nervous system in children. Three groups of
      functional proteins are known at present for regulation of the expressed enzyme
      activity in lysosomes. Targeting of a newly synthesized protein is achieved by
      the mannose 6-phosphate receptor system, which was revealed in the course of I 
      cell disease research. Many lysosomal enzymes are excessively secreted in the
      extracellular compartment in the absence of this regulatory system in patients
      with this disease. Intralysosomal stability of beta-galactosidase is regulated by
      a multifunctional protein that interacts with two lysosomal enzymes, beta
      galactosidase and sialidase, and also exerts catalytic activities as
      carboxypeptidase, esterase and deamidase under various pH conditions. It is
      encoded by a gene on chromosome 20, and its mutation results in a
      neurodegenerative disease in children and adults (galactosialidosis). For
      digestion of lipid substrates, lysosomal enzymes need specific activator proteins
      as natural detergents for molecular interaction with these nonpolar compounds.
      Two different groups of proteins have been revealed. A protein encoded by a gene
      on chromosome 5 interacts with ganglioside GM2 and its asialo derivative, for
      their catalytic hydrolysis by beta-hexosaminidase A. Another protein encoded by a
      gene on chromosome 10 is expressed as a precursor (prosaposin) which is then
      processed to four small proteins (saposins) with heterogeneous functions. They
      are essential for hydrolysis of sphingolipid substrates, and genetic deficiency
      of each protein results in various lipid storage diseases.

PMID- 8577031
TI  - [Lysosomal hydrolases have specific conformational domains for acquisition of
      mannose-6-phosphate].
AB  - In many mammalian cells, the transport of newly synthesized or externally added
      lysosomal enzymes to lysosomes is depend on their specific recognition by
      receptors for mannose 6-phosphate (Man-6-P). The physiological importance of this
      pathway was confirmed by the finding that fibroblasts from patients with
      mucolipidosis type II (ML-II ; I - cell disease) fail to phosphorylate mannose
      residues on their newly synthesized lysosomal enzymes, which results in the
      secretion of a large percentage of their acid hydrolases into the culture medium.
      However, lysosomal enzymes themselves do not contain the any consensus amino acid
      sequences for acquiring the Man-6-P recognition marker. Kornfeld et al revealed
      using cathepsin D-pepsinogen chimera proteins that UDP-N-acetylglucosamine:
      lysosomal enzyme N-acetylglucosamine-1-phosphotransferase recognizes not only
      oligosaccharides but also the three-dimensional structure of the lysosomal
      enzymes when transfers N-acetylglucosamine-1-phosphate to lysosomal acid
      hydrolases.

PMID- 8577032
TI  - [Biosynthesis, processing, and lysosome targeting of acid phosphatase].
AB  - The biosyntheses, processing, and intracellular transport of lysosomal APase were
      studied using pulse-chase experiments with primary cultured rat hepatocytes and
      subcellular fractionation techniques of rat liver after pulse-labeling with [35S]
      methionine in vivo. Apase was transported as a membrane-bound enzyme from the
      site of synthesis in the ER through the Golgi complex to lysosomes. Unlike many
      lysosomal enzymes which are translocated into lysosomes through the mediation of
      the Man-6-P receptors, transport of APase to lysosomes was independent of the Man
      6-P receptor system. The transport of APase to lysosomes is dependent on the GY
      motif which is located in its cytoplasmic domain. Kinetic experiments combined
      with subcellular fractionation of rat liver showed that after reaching the
      lysosomes, the membrane-bound APase (67 kDa) is subsequently released into the
      lysosomal matrix in the 64 kDa form, which is further processed via the 55 kDa
      form to the 48 kDa one, the major form of APase in rat liver lysosomal content.
      Our data from the in vitro experiments further showed that APase is released from
      lysosomal membranes into the lysosomal matrix by cathepsin D in the 65 kDa form,
      with release of a 1 kDa peptide, following which the released enzyme is further
      processed to the 64 kDa form, probably by lysosomal cysteine protease.

PMID- 8577033
TI  - [Metabolic pathway of the degradation of macromolecules by lysosomal enzymes].
AB  - The lysosomes of most cells function principally in intracellular digestion. They
      contain several dozens of enzymes, mostly acid hydrolyases. Vacuolar-ATPase on
      lysosomal membrane establishes low-pH environment required for efficient
      expression of hydrolyase activity. Of several dozen disorders of human and
      various animals known to be due to lysosomal dysfunctions, most of the lysosomal
      storage diseases are of genetic origin. Metabolic pathways of intracellular
      macromolecules within lysosomes have been established from studies on the
      molecular and biochemical defects on lysosomal enzymes. In the lysosomal storage
      diseases most of all, the metabolic pathways of breakdown of lipids,
      glycosaminoglycans or oligosaccharides are severely affected. The degradation
      pathways of glycoproteins, proteoglycans, and glycolipids by lysosomal enzymes
      are described in this brief review.

PMID- 8577034
TI  - [Lysosomal storage disease].
AB  - Lysosomes are the principal sites of intracellular digestion. In Lysosomes
      approximately 40 hydrolytic enzymes are contained. Lysosomal storage diseases are
      mainly caused by genetic defects that affect one or more of the lysosomal
      hydrolases, and result in accumulation of their undigested substrates in
      lysosomes, with profound pathological consequences. In this paper clinical
      features, diagnostic methods, and trend of the present research for lysosomal
      storage diseases are reviewed.

PMID- 8577035
TI  - [Biochemical diagnosis and enzymic diagnosis of lysosomal diseases].
AB  - Originally, diagnosis of lysosomal diseases was primarily based on
      clinicopathological findings and on identification of abnormally stored
      substances by analytical biochemistry. Since extraneural tissues possess only
      very low levels of sphingolipids, lipid analysis with Folch method and/or its
      modifications is usually limited to nervous system, and their applicability is
      restricted to postmortem examination and, occasionally, to verification of a
      prenatal diagnosis after abortion. On the other hand, recently developed
      TLC/enzyme immunostaining method might be useful for antemortem analysis of
      abnormally stored glycosphingolipids, because it could detect glycosphingolipids
      quantitatively with clinically available 0.5 approximately 1 ml CSF. During the
      past two decades, however, diagnostic emphasis has shifted to enzymic assay,
      which provide relatively easy, noninvasive antemortem diagnosis because
      clinically available enzyme sources, such as serum, leukocytes and cultured
      fibroblasts, and also commercially available artificial substrates can be used.
      These procedures can be used to detect heterozygous carriers. Identification of
      affected fetus during early pregnancy is generally possible with similar
      procedures.

PMID- 8577036
TI  - [Gene diagnosis of lysosomal diseases].
AB  - Molecular genetic analysis of lysosomal storage diseases has revealed numerous
      mutant genes for each disease, and the results have been applied to gene
      diagnosis in patients and their family members. In general, the same mutant gene
      is not always found in different families. Confirmation of a mutant gene is
      necessary for each proband case in a family, although some common mutations can
      be screened for patients in a specific ethnic population, such as 151T mutation
      of the beta-galactosidase gene among Japanese cases of adult GM1-gangliosidosis.
      The result of gene analysis is generally clear and provides a solid diagnosis for
      each member at risk in a family. Gene analysis and conventional enzyme assays
      should be performed in a mutually complementary manner for laboratory diagnosis
      of lysosomal diseases.

PMID- 8577037
TI  - [Prenatal diagnosis of lysosomal diseases].

PMID- 8577038
TI  - [Screening methods for the diagnosis of lysosomal storage disease].
AB  - Lysosomal storage disease is one of the inborn errors of metabolism caused by a
      deficiency of lysosomal acid hydrolase activity. We describe here the details of
      screening methods for the diagnosis of this disorder. It is definitely important
      to perform both enzyme assay of acid hydrolases and the detection of accumulated
      materials in patient's tissues. Leukocytes (lymphocytes), serum or plasma, and
      cultured skin fibroblasts are commonly used as the enzyme source for the assay.
      Although most lysosomal storage diseases can be diagnosed using leukocytes as the
      enzyme source, enzymatic activities of beta-glucosidase and sialidase in
      leukocytes are sometimes normal even in patients. At present, the most reliable
      enzyme source is considered to be cultured skin fibroblasts. Nevertheless, we
      should remind that we cannot detect a deficiency of galactocerebroside beta
      galactosidase activity even using fibroblasts, if we use synthetic substrate.
      Natural substrates should be employed for the correct diagnosis and for the study
      of the nature of patient's enzyme. Deficiency of the enzymatic activity in
      patients should be confirmed by the demonstration of accumulated materials due to
      the enzyme defect in patient's tissues and urine. The accumulation of
      mucopolysaccharides and oligosaccharides in urine is obvious in patients with
      mucopolysaccharidoses and mucolipidoses, respectively. In case of
      sphingolipidoses, rectal biopsy specimen and blood could be a target of the
      investigation. In final, the choice of these screening methods should be made
      solely based on the detailed clinical manifestation of patients.

PMID- 8577039
TI  - [Glycogenosis type II; acid alpha-glucosidase deficiency].
AB  - Knowledge of the general enzymology of lysosomal acid alpha-glucosidase (acid
      maltase) including that of the intracellular processing mechanism and of the cDNA
      sequence has advanced recently. Genetic heterogeneity of the mRNA of acid alpha
      glucosidase deficient patients has also been reported. Referring to these recent
      advances, and based on our previously reported results, the pathologic aspects of
      the disease are reviewed. Heterogeneity of the enzyme molecules themselves and
      their characteristics in various tissues are also demonstrated.

PMID- 8577040
TI  - [Gaucher disease].
AB  - Gaucher disease is an inherited metabolic disease characterized by deficient
      activity of lysosomal enzyme, known as a glucocerebrosidase. Three clinical
      phenotype were documented depends on the onset of disease and neuronal
      involvement. Deficient activity of glucocerebrosidase results in progressive
      accumulation of glucocerebroside mainly in bone marrow derived macrophages.
      Diagnosis was made based on enzymatic activity in various tissue including WBC
      and fibroblasts. Molecular diagnosis was also possible. However, it is difficult
      to differentiate the three phenotypes. Although bone marrow transplantation and
      enzyme infusion therapy are both effective, the inherent problems limits their
      application. Gene therapy based on transfer of the therapeutic gene to
      hematopoietic stem cells were started in this year in USA.

PMID- 8577041
TI  - [Krabbe disease (globoid cell leukodystrophy)].
AB  - Krabbe disease is an autosomal recessive inherited demyelinating disease, which
      is deficient in lysosomal enzyme, galactocerebrosidase. Pathophysiological
      characteristics of this disease are extreme demyelination in white matter and
      peripheral nerve, existence of globoid cells, absence of accumulation of main
      substrates, i.e. galactocerebrosidase in tissues and accumulation of psychosine.
      Molecular basis of this disease including isolation of a cDNA for human and
      murine galactocerebrosidase and cloning of genome of this gene are reviewed. The
      trial of gene therapy on twitcher, the mouse model of Krabbe disease, could break
      through on therapy on this progressive demyelinating disease.

PMID- 8577042
TI  - [Fabry disease (alpha-galactosidase deficiency)].
AB  - Fabry disease is an X-linked glycosphingolipid storage disorder resulting from a
      deficiency of lysosomal alpha-galactosidase (alpha-Gal; EC 3.2.1.22). Classical
      form patients, with clinical manifestations of generalized angiopathy of early
      onset, usually show no detectable alpha-Gal activity. There are also atypical
      form patients with residual alpha-Gal activity and late onset cardiomyopathy
      without other systemic manifestations. We identified a number of alpha-Gal gene
      mutations including partial deletions and point mutations. They were
      heterogeneous and more than half of them were missense mutations. Various
      missense mutants were expressed in COS-1 cells. Two groups have been identified;
      one expressing a mutant enzyme without catalytic activity, and the other
      expressing a catalytically active but unstable mutant enzyme. The latter was
      restored in patient cells by the addition of substrate analogues. The molecular
      genetic and biochemical analysis for Fabry disease will provide us with
      significant informations on the pathogenesis and the possibility of the
      therapeutic approach for this disease.

PMID- 8577043
TI  - [beta-galactosidosis--GM1 gangliosidosis and Morquio B disease].
AB  - beta-galactosidosis is a lysosomal storage disorder caused by a deficiency of
      acid beta-galactosidase, including to autosomal recessive diseases; GM1
      gangliosidosis (neurovisceral form) and Morquio B disease (skeletal form). To
      date, 26 different mutations in the beta-galactosidase gene have been identified
      in patients with beta-galactosidosis from various ethnic groups. Transient
      expression of the mutant genes has confirmed that mutant enzymes responsible for
      infantile GM1-gangliosidosis have almost no detectable beta-galactosidase
      activity. But the other three forms (late infantile/juvenile, adult/chronic GM1
      gangliosidosis and Morquio B disease) are characterized by specific mutant
      enzymes with significant residual enzyme activity. Heterogeneous patterns of post
      translational processing and maturation in these mutant enzymes are closely
      related to the phenotypic variations in beta-galactosidosis.

PMID- 8577044
TI  - [Galactosialidosis--protective protein and related enzymes].
AB  - Galactosialidosis is the inherited metabolic disease with autosomal recessive
      trait. This disease classifies into three classical subtypes and a variant type
      in clinically. In enzymatic assay, we observe the decreasing activities of both
      beta-galactosidase and neuraminidase, but now we know that the primarily cause of
      this disease is abnormality of protective protein. In 1988, the cDNA of human
      protective protein was cloned. From the cloning, the genetically abnormalities of
      this disease were detected and the difference of abnormalities about the proteins
      were studied between the clinical subtypes. Then, the abnormalities within the
      subtypes were confirmed the difference about the mature process of protective
      protein in expression study. The structure of this protein was shown in 1994-1995
      and the abnormal mutated proteins were studied about stoichiometrical features.
      On the other hand, the functions of protective protein are identified to have the
      role of deamidase, esterase, and carboxypeptidase besides the protective
      function. In the galactosialidosis patients, these activities decrease in fact.
      We knew the reason of the difference within the subtypes of this disease using
      molecular biology methods at present. In the future, the model mouse will be
      prepared and we hope to produce the medicine for this disease.

PMID- 8577045
TI  - [Disorders of glycoprotein degradation].
AB  - Glycoprotein consist of oligosaccharides chains covalently attached to the
      polypeptide backbone. They are synthesized by two pathways; sugar nucleotide
      pathway and dolichol pathway. The degradation of glycoproteins occurs
      predominantly in the lysosomes through the ordered actions of lysosomal
      proteases, glycosidases, and aspartylglucosaminidase. Genetic deficiencies of
      these enzymes cause progressive accumulation of partially degraded
      oligosaccharides and glycopeptides, resulting in specific lysosomal storage
      diseases. Clinically, the diseases are characterized by the various degree of
      mental retardation, coarse facies, dysostosis multiplex, and visceromegaly.
      Although the urinary screening test for storage compounds is highly supportive,
      the definitive diagnosis of the disease is based on the measurement of lysosomal
      enzyme activity. This paper presents the review of clinical and biochemical
      features of this group of diseases including alpha-mannosidosis, beta
      mannosidosis, fucosidosis, sialidosis, and aspartylglucosaminuria. Recent
      advances in molecular genetics in fucosidosis and aspartylglucosaminuria are also
      reviewed.

PMID- 8577046
TI  - [Schindler disease/Kanzaki disease].
AB  - Schindler disease and Kanzaki disease are caused by a deficient lysosomal enzyme,
      alpha-N-acetylgalactosaminidase (E.C.3.2.1.49). Two German children were first
      reported in 1987 and other two Dutch children were recently reported in 1993.
      These children were very similar clinically and characterized by maked
      neuroaxonal dystrophy of an infantile onset. This disease (type 1) was named
      Schindler disease. On the other hand, an adult patient with profuse angiokeratoma
      corporis diffusum but minimum involvement in nervous system was reported in 1987
      from Japan. This disease (type 2) was named Kanzaki disease (Mckusick catalog No.
      104170). Molecular analyses of these diseases revealed one each point mutation in
      the encoding gene. Clinical, ultrastructural and molecular studies of these
      disease were described.

PMID- 8577047
TI  - [Recent advances in molecular genetics of GM2 gangliosidosis].
AB  - Recent advances in molecular genetics of GM2 gangliosidosis are reviewed. GM2
      gangliosidosis is an autosomal recessive, neurodegenerative disease caused by a
      deficiency of beta-hexosaminidase (Hex, EC 3.2.1.52) A activity, resulting in
      accumulation of GM2 ganglioside in the lysosomes of neuronal cells. There are two
      catalytically active forms of this enzyme: Hex A, composed of one alpha and one
      beta subunits. Three forms of this disease, Tay-Sachs disease, Sandhoff disease,
      and GM2 activator deficiency, have been recognized according to whether the
      defect involves the alpha subunit, beta subunit, or GM2 activator protein,
      respectively. A number of gene abnormalities responsible for the disease have
      been identified and mutations specific for phenotypes and racial backgrounds are
      summarized. Recently, the murine models of human Tay-Sachs disease and Sandhoff
      disease have been produced. With the finding of dramatically clinical phenotypes
      in these mice, these models could be useful for research on the pathogenesis or
      therapy of these diseases.

PMID- 8577049
TI  - [Acid lipase deficiency: Wolman disease and cholesteryl ester storage disease].
AB  - Wolman disease and cholesteryl ester storage disease (CESD) are caused by a
      deficiency of lysosomal acid lipase activity, resulting in massive accumulation
      of cholesteryl ester and triglycerides. Wolman disease occurs in infancy, with
      hepatosplenomegaly, steatorrhea and adrenal calcification. It is fatal before the
      age of 1 year. In CESD, hepatomegaly may be the only clinical abnormality,
      although lipid deposition is widespread. Lysosomal acid lipase hydrolyzes both
      triaclyglycerols and cholesteryl esters, and the enzyme plays an important role
      in the cellular processing of plasma lipoproteins, and contributes to homeostatic
      control of lipoprotein levels in blood and prevention of cellular lipid
      overloading. The gene encoding lysosomal acid lipase was cloned and characterized
      in 1994, and two mutations of acid lipase gene were found in a patient with
      Wolman disease, as a compound heterozygote. It is suggested that structural gene
      defects are also present in CESD cells. However, the reason (s) for the clinical
      difference between Wolman disease and CESD remain (s) to be studied.

PMID- 8577048
TI  - [Metachromatic leukodystrophy (MLD) and Multiple sulphatase deficiency (MSD)].
AB  - MLD is caused by a deficiency of arylsulfatase A and hence sulfolipids are
      accumulated in various patient's tissues. Various clinical phenotypes including
      activator deficiency, pseudodeficiency and MSD. Recently, molecular basis of
      these disorders have been identified. Clinical phenotype in MLD is well
      correlated with their genotype. Most common mutation in Caucasian MLD is caused
      by 609A mutation which produces late infantile MLD. In Japanese, most common
      mutation is 445A mutation. Essential treatment of MLD is recently carried out by
      bone marrow transplantation. On the hand, MSD is caused by multiple deficiencies
      of various sulfatases and hence accumulated various sulfated compounds such as
      sulfatide and acid mucopolysaccharides. The clinical features have combined
      characteristics of MLD and mucopolysaccharidosis. The cause of this disorder is
      recently identified as abnormal modification of various sulfatase.

PMID- 8577050
TI  - [Farber's lipogranulomatosis].
AB  - Farber's lipogranulomatosis is a disorder of lipid metabolism due to deficiency
      of lysosomal acid ceramidase. Since Farber described the first case in 1947, at
      least 50 cases have been reported. Clinical manifestations include progressive
      arthropathies with periarticular swelling, hoarse voice, multiple subcutaneous
      nodules and growth and developmental retardation. The histological findings
      indicate granuloma formation with infiltrated lipid-laden macrophages and
      fibroblasts. Curvilinear tubular structures, so-called "Farber bodies", are
      observed on electron microscopy. The specific diagnosis can be made by
      demonstration of a deficiency of acid ceramidase, ceramide accumulation in tissue
      or characteristic morphological features on biopsy or postmortem specimens. Bone
      marrow transplantation may be effective during the early stage of this disease.

PMID- 8577051
TI  - [Niemann-Pick disease types A and B].
AB  - The molecular basis of Niemann-Pick disease, type A and B, has been confirmed by
      detection of mutations causing deficiency of the acid sphingomyelinase activity
      in the patients. It has been shown that mutations, which cause no activity of
      acid sphingomyelinase, are responsible for the type A and mutations which cause
      residual activities of the enzyme are responsible for the type B. Acid
      sphingomyelinase deficient mice have been established and confirmed to show a
      similar abnormality observed in human disease type A. These knock-out mice should
      serves as a useful model for somatic gene therapy. The mechanism of neuronal cell
      dysfunctions in the type A patients has not been well-characterized. Progress
      suggest that ceramide, which is produced by sphingomyelinase from sphingomyelin,
      is an important factor for signal transduction of cell differentiation. In
      addition, a lysosphingolipid (sphingosylphocholine), which accumulates in the
      tissues of the patients, has been reported to act as a strong mitogen in several
      types of cells through activating a transcription factor. AP-1. It is possible
      that abnormal phospholipid signaling is involved in the pathogenesis of neuronal
      cell dysfunction of Niemann-Pick disease type A.

PMID- 8577052
TI  - [Mucopolysaccharidoses].
AB  - Mucopolysaccharidoses (MPS) are a lysosomal storage disorders caused by
      deficiency of several enzymes needed for degradation of mucopolysaccharides
      (glycosaminoglycans). Undegraded glycosaminoglycans accumulate in the cell, part
      of which are excreted into the urine. There are 10 known enzyme deficiencies that
      give rise to six distinct MPS. Despite the different enzyme defect, there is
      clinical similarity between different deficiencies and conversely, wide
      phenotypic variety among even one enzyme deficiency. Most of the cDNAs
      corresponding the defect enzyme as well as genomic DNA have been cloned.
      Mutational analyses of the patient gene have revealed the molecular basis of the
      disease, correlation of the genotype and phenotype and made the accurate
      heterozygote diagnosis feasible. Supportive management can greatly improve the
      quality of life and moreover, development of therapies, such as BMT,
      administration of recombinant enzyme and gene transfer are in progress for the
      patients suffering from MPS.

PMID- 8577053
TI  - [Disorders of sphingolipid activator proteins].
AB  - Small-molecular nonenzymatic glycoproteins are necessary for degradation of
      sphingolipids in lysosomes. GM2 activator encoded by a gene on chromosome 5 is
      essential for hydrolysis of ganglioside GM2 and its asialo derivative. Mutations
      of this gene cause Tay-Sachs disease-like clinical phenotype (GM2-gangliosidosis
      AB variant). Another gene on chromosome 10 codes for a protein called prosaposin,
      which is then processed to four related but independent activator proteins;
      saposin A, B, C, and D. These five proteins show different molecular functions,
      and their mutations cause diseases with prosaposin deficiency (clinically similar
      to Gaucher disease type 2), and saposin C deficiency (clinically similar to
      Gaucher disease type 3). They are rare genetic disorders, but provide information
      about molecular events between the enzyme and substrate in lysosomes.

PMID- 8577054
TI  - [I-cell disease and pseudo-Hurler polydystrophy].
AB  - I-cell disease (ML II) and pseudo-Hurler poly-dystrophy (ML-III) are lysosomal
      storage diseases caused by abnormal lysosomal enzyme phosphorylation and
      localization. In both diseases, newly synthesized lysosomal enzymes are secreted
      into the extra-cellular medium instead of being targeted correctly to lysosomes.
      All cells and tissues of affected medium instead of being targeted correctly to
      lysosomes. All cells and tissues of affected patients are deficient in UDP-N
      acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase
      activity. However, we have demonstrated that liver cells from ML II patients have
      normal lysosomal enzyme contents. In Japan, ML II is a relatively common disorder
      whereas ML III is very rare as compared to Western Countries. The natural history
      of 21 cases with ML II, as well as 5 prenatally diagnosed cases of ML II, have
      been reported by our research group.

PMID- 8577055
TI  - [Niemann-Pick disease type C].
AB  - Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid
      storage disorder, but the basic defect has not yet been clarified. Diagnostic
      biochemical makers are intracellular accumulation of free cholesterol or the
      decreased esterification of exogenous cholesterol. The differences in the
      severity of defective esterification are related to the onset of the disease.
      Genetically, an abnormal gene is located on the human chromosome 18.
      Biochemically, many drugs, i.e. imipraine, progesterone and bafilomycin A1 are
      known to interfere with cholesterol esterification. Clinically, vertical
      supranuclear gaze palsy and cataplexy are specific symptoms. The filipin stain of
      the foamy cell in bone marrow is available for rapid diagnosis. Many therapies,
      i.e. dimethyl sulfoxide, low-cholesterol diet and transplantations, have been
      challenged but improvement of neurological symptoms have not been reported.

PMID- 8577056
TI  - [Carbohydrate-deficient glycoprotein syndrome].
AB  - Carbohydrate-deficient glycoprotein syndrome is characterized by mental
      retardation, ataxia, hepatopathy during infancy, cerebellar hypoplasia,
      peripheral neuropathy, internal strabismus, growth retardation and stroke-like
      episodes. Since the description of female siblings with unique clinical and
      biochemical features by Jaeken (1980) and the discovery of unique isoforms of
      serum transferrin in the patients by Jaeken (1984), more than 120 patients have
      been diagnosed. The biochemical marker is asialo- and disialo-transferrin. We
      have found the first Japanese patients and, through analysing serum glycoproteins
      from these patients, we was noted that multiple serum glycoproteins contain
      abnormal fractions, on isoelectric focusing. By analysing the sugar chain of
      transferrin, we have found that the abnormality is caused by a defect in the
      transfer of asparagine-N-linked oligosaccharide. Recently, two clinical and
      biochemical variants have been reported. One, characterized by severe mental
      retardation, no cerebellar hypoplasia, no peripheral neuropathy,
      diasirotransferrin dominancy, has proven to have a deficiency of N
      acetylglucosaminyltransferase II, by Jaeken (1993).

PMID- 8577057
TI  - [Lysosomal glycogen storage disease without acid maltase deficiency].
AB  - Lysosomal glycogen storage disease without acid maltase deficiency is
      characterized by the triad of clinical manifestations (hypertrophic
      cardiomyopathy), mental retardation, and mild myopathy), morphologic findings
      (glycogen storage, glycogenosomes, and autophagic vacuoles), and normal
      glycolytic enzyme activities. Though most of the patients suffering from the
      triad were males, family studies often revealed female patients with only
      cardiomyopathy. So far 27 cases have been reported. The cardiac involvement is
      progressive and fatal and as severe in females as in males. Many patients of both
      sexes die in their youth, unexpectedly, because of cardiac failure. The specific
      biochemical defect causing this disease remains unknown. From abnormal lectin
      staining patterns on the membrane and preclinical morphologic changes in biopsied
      skeletal muscle, membranous abnormality is suspected in this disease.

PMID- 8577058
TI  - [Batten disease (Neuronal ceroid lipofuscinoses)--accumulation of ATP synthase
      subunit c caused by the delay of lysosomal degradation].
AB  - The neuronal ceroid lipofuscinoses (NCLs) represent a group of recessively
      inherited neurogenerative diseases of infants, children, and young adults that
      leads to blindness, seizures, dementia, and premature death. These diseases are
      pathologically characterized by a massive lysosomal storage of autofluorescent
      lipopigments in neurons and a wide variety of extraneuronal cells. Linkage
      studies have shown localization of the infantile disease to chromosome region
      1p32 the juvenile onset disease to chromosome 16p12.1-p11.2 and a variant form of
      late infantile form to chromosome 13q21.1-q32. Recently, protein sequencing and
      immunochemical studies have identified subunit c of the mitochondrial ATP
      synthase as a major component of the storage material in the late infantile and
      juvenile types of NCL, and SAPs in infantile type of NCL. Immunolocalization
      studies demonstrated a dot-like staining of subunit c in the cells with NCL and
      the staining pattern of subunit c was similar to that of a lysosomal membrane
      marker, 1gp120. Pulse-chase experiments revealed that a specific failure occurs
      in the degradation of subunit c in lysosomes whereas its transport into
      mitochondria and subsequent sequestration into lysosomes are apparently normal.

PMID- 8577059
TI  - [Lysosomal storage diseases with angiokeratoma corporis diffusum].
AB  - There are 6 well known lysosomal storage diseases which produce angiokeratoma
      corporis diffusum clinically. The clinical, histological, ultrastructural and
      biochemical characteristics are discussed. The best known angiokeratoma will be
      observed in patients with Fabry disease. Angiokeratoma in Fabry disease, however,
      may be much fewer than thought previously. Fucosidosis and galactosialidosis are
      next well known diseases to produce angiokeratoma. Approximately 50% of patients
      with these diseases have angiokeratoma. Recently reported Kanzaki disease, beta
      mannosidosis and aspartylglucosaminuria will show angiokeratoma more or less
      extensively. Ultrastructurally Fabry disease only produce electron dense deposits
      in lysosomes and others electron lucent. These are summarized in Table 1 in the
      text.

PMID- 8577060
TI  - [Lysosomal membrane transport disorders--cystinosis and sialic acid storage
      disorders (Salla disease, ISSD)].
AB  - Cystinosis and sialic acid storage diseases (Salla disease, ISSD; infantile
      sialic acid storage disease) are lysosomal membrane disorders resulting from
      defective carrier-mediated transport of cystine and sialic acid across the
      lysosomal membrane. Both are rare autosomal recessively inherited disorders. The
      major clinical manifestations of cystinosis are renal failure and ocular damages.
      Sialic acid storage diseases are characterized by various degrees of psychomotor
      retardation. Salla disease patients trace a mild clinical course, and the life
      span is relatively long. While, in patients with ISSD follow a very severe
      progressive clinical course and often die in the first year of life. The genes
      responsible for each disease have not been isolated, the etiologies are not well
      known, and there is no specific treatment.

PMID- 8577061
TI  - [Medicinal therapy for lysosomal storage diseases].
AB  - Lysosomes contain several dozen different enzymes, mostly acid hydrolases.
      Materials not digested due to deficient lysosomal enzymes are usually large
      cellular molecules, which are deposited within the cells. The strategy for
      medicinal therapy of lysosomal storages disease may be to develop the activators
      of enzymes, to promote coenzyme and cofactor supplementation and to eliminate
      undegraded materials from blood into urine. In the last several decades, many
      trials for these strategies has been done. Cysteamine for cystinosis and
      penicillamine for Wilson's disease has proved useful in treating these patients.
      Recently, DMSO has been proved to be an activator of acid sphingomyelinase and to
      accelerate the intracellular mobilization of LDL-derived cholesterol. We treated
      patients with Niemann-Pick disease type C by oral administration of DMSO,
      resulting in some clinical benefits such as decreased size of hepatosplenomegaly,
      and lesser frequency of seizures with improved EEG. However, the progressive
      clinical course has not been changed although it appeared to slow down. New
      activators of lysosomal enzymes should be developed for medicinal therapy of
      lysosomal storage diseases.

PMID- 8577062
TI  - [Enzyme replacement therapy of patients with lysosomal storage disease].
AB  - The history and bases of enzyme replacement therapy are briefly reviewed. The
      enzyme replacement therapy for Gaucher disease type 1, which has been developed
      for clinical use and is about to be introduced in our country, was described
      somewhat in detail under the items of the modification of human placental
      glucocerebrosidase into the macrophage-terminated enzyme, its clinical usage,
      effects and their evaluations, adverse effects, and new attempts of its
      application for Gaucher disease types II and III, now being under clinical
      trials. Also touched are developments of other enzymes for such lysosomal
      diseases as Fabry disease, Pompe disease, Hurler syndrome, Hunter disease, and
      Sly disease.

PMID- 8577063
TI  - [Bone marrow transplantation for lysosomal storage diseases].
AB  - Since a successful bone marrow transplantation (BMT) for Hurler's disease
      reported in 1981, BMT has been established as an effective treatment for
      lysosomal storage diseases such as mucopolysaccharidosis or lipidosis. In
      general, BMT can improve the somatic disease, but the neurologic and intelligence
      outcomes vary widely. The understanding on whether transfer of a lysosomal
      hydrolase to CNS neurons can occur is indispensable to a proper prediction on CNS
      improvement. Furthermore the long-term therapeutic effects of BMT can be subject
      to multiple factors including a level of biochemical improvement, a reversibility
      of affected tissues, or a degree of advanced disease prior to BMT. Thus, an
      accumulation of clinical and biochemical follow-up study is needed to understand
      the therapeutic efficacy and consequence of BMT for lysosomal storage diseases.

PMID- 8577064
TI  - [Gene therapy for Gaucher disease].
AB  - Gaucher disease is a lysosomal storage disease which is characterized by
      deficient activity of lysosomal enzyme, known as glucocerebrosidase. This
      resulted in progressive accumulation of glucocerebroside only in bone marrow
      derived macrophages. This unique pathophysiology makes Gaucher disease an
      excellent candidate of gene therapy based on transferring therapeutic gene to
      hematopoietic stem cell. The extensive study based on transferring therapeutic
      gene to hematopoietic stem cell. The extensive study was already done using mouse
      in vivo system and human in vitro system. In mouse system, all of the macrophages
      from long term reconstituted mice were transduced. In human system, 40
      approximately 60% of bone marrow progenitor cells were transduced. Because of
      this success, the clinical protocol for gene therapy for Gaucher disease was
      approved by RAC and FDA. The clinical trial was started in this year. The brief
      history of development and current limitation of gene therapy for Gaucher disease
      were discussed.

PMID- 8577065
TI  - [Glycolipid analysis by confocal laser scanning microscopic system].
AB  - The combined use of immunofluorescence method with oligosaccharide-specific
      monoclonal antibodies against glycolipids and a confocal laser scanning
      microscopic system was successful to detect the storage of glycolipids in
      cultured cells derived from patients with lysosomal diseases. The accumulated
      glycolipids were observed stereoscopically as granular inclusions in the cells.
      An immunofluorometric semiquantative determination was achieved of
      globotriaosylceramide in cultured fibroblasts from Fabry disease patients or GM2
      ganglioside in cultured amniocytes from Tay-Sachs disease. Heterozygote
      identification of the former disease or prenatal diagnosis of the latter one were
      confirmed by counting immunoreactive cells or by digital imaging analysis. The
      present immunofluorescence method is applicable to the diagnosis of the other
      lipidosis with accumulation of the specific glycolipids.

PMID- 8577066
TI  - [The metabolism of radiolabelled GM1-ganglioside in cultured skin fibroblasts
      from controls and patients with GM1-gangliosidosis].
AB  - The metabolism of [3-3H-sphingosine] GM1-ganglioside was studied in cultured skin
      fibroblasts from control and patients with beta-galactosidase deficiency,
      primarily or secondarily. When dissolved in the medium with phosphatidylserine,
      GM1-ganglioside was efficiently taken up by cultured skin fibroblasts and
      transferred into lysosomes. A pulse-chase study revealed that [3-3H-sphingosine]
      GM1-ganglioside was metabolized to GM2-, GM3-ganglioside, ceramide, ceramide
      monohexoside, ceramide dihexoside and sphingomyelin. In a 20h pulse study, cell
      lines from patients with GM1-gangliosidosis of infantile, juvenile and adult
      types hydrolyzed 2 approximately 5%, 20 approximately 44% and 54 approximately
      58% of the total endocytosed GM1-ganglioside respectively. These values were
      lower than in the control cells (62.2 +/- 5.43% (n=10). The hydrolysis rates of
      exogenous [3-3H-sphingosine] GM1-ganglioside in cultured skin fibroblasts from
      various types of GM1-gangliosidosis closely correlated to the clinical severity.
      This method is also useful to the diagnosis of impaired ganglioside metabolism.

PMID- 8577067
TI  - [Mini review: animal model of human lysosomal storage disease].
AB  - A number of true genetic animal model of human inborn errors of metabolism,
      caused by a specific enzyme defect are known. Recently, in addition to the
      naturally occurring diseases of animals, genetic engineering techniques such as
      transgenic or gene targetting, provide the animal models with specific gene
      defect. Such animal systems with lysosomal enzyme defect are summarized herein.
      Several animal model systems with lysosomal enzyme defect have been used to study
      the therapeutic strategies such as bone marrow transplantation and/or gene
      therapy. In this review, mucopolysaccharidosis VII mice treated with bone marrow
      transplantation and gene therapy, mucopolysaccharidosis VI rats and Niemann-Pick
      type C mice treated with bone marrow transplantation are mainly introduced. The
      latter two animals were established in Japan.

PMID- 8577068
TI  - [Apoptosis: its molecular mechanisms and biological roles].
AB  - Apoptosis is a mechanism for eliminating unwanted cells from the cell community
      of multicellular organisms. Abnormalities in the regulation of apoptosis may play
      a part in the aetiology of cancer, autoimmune diseases, AIDS, degenerative nerve
      diseases and malformation. On of the hallmarks of apoptosis is the enzymatic
      cleavage of genomic DNA into nucleosomal oligomers. The identification of an
      endonuclease responsible for apoptosis might help to explain how this cell
      suicide is regulated and why DNA is cleaved. Here, we found that gamma type of
      DNase was retained in apoptotic rat thymocyte nuclei. The mode of DNA cleavage,
      3'-hydroxyl (OH)/5'-phosphoryl (P) ends, by homogeneously purified DNase gamma
      (Mr = 33 kDa) and its Zn2+ sensitivity match those observed in apoptosis in
      thymocytes induced by irradiation or glucocorticoid treatment, indicating that
      this endonuclease is a central component of the thymic apoptosis machinery.

PMID- 8577069
TI  - [Construction and clinical application of chimeric antibodies].
AB  - To reduce the high immunogenicity of mouse monoclonal antibodies (MAbs) in man,
      mouse/human chimeric antibodies have been generated in two ways. The more simple
      method is to construct chimeric antibodies in which the variable regions from the
      mouse MAbs are linked to human constant regions. The second is to graft the
      complementarity determining regions from the variable regions of mouse MAbs into
      human variable regions. So far, more than a hundred of chimeric antibodies have
      been reported and about twenty-five have been tried for immunotherapy of various
      human diseases. In the near future, many mouse/human chimeric antibodies will be
      commercially available.

PMID- 8577070
TI  - The motoneurons innervating the musculus levator palpebrae superiors in the
      monkey, cat and rabbit.
AB  - The motoneurons innervating the musculus levator palpebrae superioris (LPS) of
      the monkey, the cat and the rabbit were studied using horseradish peroxidase
      (HRP). Furthermore, LPS motoneurons of the cat and rabbit were studied by the
      double-labeling method using two fluorescent dyes as retrograde neuronal tracers.
      After injection of HRP into the right LPS of the monkey and the cat, HRP-labeled
      neurons were found only in the central caudal nucleus with contralateral
      preponderance. In contrast, after HRP injection into the right LPS of the rabbit,
      HRP-labeled neurons were found only in the contralateral oculomotor nucleus. In
      the double-labeling study, after injection of fast blue (FB) into the right LPS
      and diamidino yellow dihydrochloride (DY) into the left LPS of the cat and the
      rabbit, no double-labeled neurons were noted in the central caudal nucleus of the
      cat nor in the oculomotor nucleus of the rabbit, although double-labeled neurons
      were identified in the central caudal nucleus of the monkey in our previous
      study. Cross-innervation was confirmed in the mammals lower than the monkey.

PMID- 8577071
TI  - Proton nuclear magnetic resonance study on the barrier function of pig corneal
      epithelium and endothelium.
AB  - Using gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) as a tracer, the
      barrier function of the corneal epithelium and endothelium was evaluated by
      proton nuclear magnetic resonance. Whole pig eyes and cornea excised with scleral
      rim, which had been incubated in dextran-added Gd-DTPA solution, were subjected
      to T1 relaxation measurement and magnetic resonance imaging (MRI). After
      incubation, the T1 relaxation rate (1/T1) of the excised cornea increased to a
      steady value, whereas that of the cornea from the whole eye increased only
      slightly. These results indicated that the increase in the T1 relaxation rate of
      the excised cornea attributable to Gd-DTPA penetration from the corneal
      endothelium and that the corneal epithelium exhibited a strong barrier function
      against Gd-DTPA entry. The MRI study also confirmed the strong barrier, enhanced
      signals being detected within the aqueous fluid in the T1-weighted image only
      when the corneal epithelium was abraded. Since Gd-DTPA scarcely penetrates the
      intact corneal epithelium, Gd-DTPA-enhanced MRI shows potential as a quantitative
      tracer in evaluating epithelial barrier disruption.

PMID- 8577072
TI  - Regulation of glucose transporter 1 (GLUT1) gene expression by epidermal growth
      factor in bovine corneal endothelial cells.
AB  - The regulation mechanism of glucose transporter 1 (GLUT1) gene expression was
      investigated in cultured bovine corneal endothelial cells. Epidermal growth
      factor (EGF) stimulated both GLUT1 mRNA expression and cell proliferation. Fetal
      bovine serum, in contrast, stimulated cell proliferation but did not increase
      GLUT1 mRNA. IGF-I, hyaluronic acid or fibronectin did not stimulate GLUT1 gene
      expression. These results suggest that GLUT1 gene expression is controlled, at
      least in part, by EGF and is related to neither cell proliferation, cell motility
      nor cell adhesion regulation. The EGF signal was transduced through a pathway
      including protein kinase C. GLUT1 is reported to work as a water transporter, and
      so EGF can be considered as one of the possible agent which stimulate water
      transport activity through the corneal endothelial cells. EGF could be useful in
      the therapy of corneal edema caused by endothelial dysfunction.

PMID- 8577073
TI  - The effects of endothelin-1 on intraocular pressure and pupillary diameter in
      rabbits.
AB  - Endothelin-1 (ET-1) reduced intraocular pressure (IOP) in animals when
      administered topically. The time-course of IOP changes induced by ET-1, however,
      has not been fully documented. We studied the IOP response to different doses of
      intravitreally injected ET-1 ranging from 10(-7) to 10(-4) M in rabbits. In each
      animal one eye received 20 muL of ET-1 solution and the contralateral eye
      received the same amount of vehicle in a randomized, masked fashion. IOP was
      measured by a pneumatonometer prior to and periodically for at least 72 hours
      after the intravitreal injection. ET-1 in 10(-4) and 10(-5) M concentration
      elicited an IOP response consisting of an initial rise of 1- to 2-hour duration,
      and a subsequent prolonged reduction lasting for more than 72 hours. The use of 3
      x 10(-6) and 10(-6) M solutions resulted in a prolonged IOP reduction without an
      early IOP rise. No significant IOP change was induced by 10(-7) M solution or the
      vehicle. No change was observed in pupillary diameters after injection of ET-1 in
      any dose. The aqueous prostaglandin E2 concentration was significantly increased
      at both 1 and 24 hours after 10(-5) M ET-1 injection.

PMID- 8577074
TI  - Isoforms of glucose transporter in the iris-ciliary body.
AB  - Isoforms of the facilitated glucose transporter (GLUT) were identified in the
      iris-ciliary body. Western blot analysis showed that GLUT1 and GLUT4 proteins
      were expressed in the rat iris-ciliary body. In addition, the content of GLUT
      proteins in the rabbit iris-ciliary body was estimated by specific
      [3H]cytochalasin B binding assay. The content of GLUT proteins was found to be
      more abundant in the iris-ciliary body than in the cerebral cortex. The
      utilization of glucose in the iris-ciliary body and the transport of glucose into
      the aqueous humor are suggested to be mediated by GLUT1 and GLUT4 proteins.

PMID- 8577075
TI  - Differential expression of mRNA for alpha 2,3-sialyltransferase during
      development of rat retina.
AB  - Glycoconjugates, consisting of O- and N-linked types, are present on the surface
      of photoreceptor cells and in the interphotoreceptor matrix (IPM). This study was
      undertaken to facilitate understanding of the metabolic features of O-linked
      sialoglycoconjugates in comparison with those of N-linked glycoconjugates in the
      rat retina. We examined the developmental change in distribution of Gal beta
      1,3GalNAc alpha 2,3-sialyltransferase mRNA in rat retinas using in situ
      hybridization histochemistry to detect the synthesis period of O-linked
      sialoglycans. Positive hybridization signal was observed in the ganglion cells
      throughout the postnatal days (P) examined, whereas strong signals were detected
      in the photoreceptor inner segments and the inner nuclear layer exclusively at
      P16 and P18. At P20 and older, weak or sparse signals were detected in these
      regions. It is likely that O-linked sialoglycoconjugates, which are detected in
      the mature IPM, are actively synthesized from P16 to P18 in the rat photoreceptor
      inner segments, suggesting that the O-linked sialoglycoconjugates in the
      photoreceptor layer may be stable with litter turnover in the mature retina.

PMID- 8577076
TI  - Recovery of photopic ERG from pressure-induced retinal ischemia in rabbit eyes.
AB  - Using precise experimental methods, we evaluated the recovery from pressure
      induced ischemia in rabbit retina using photopic electroretinography (ERG). The
      recovery was evaluated and documented in terms of the increasing amplitude and
      the decreasing delay of implicit time in the photopic ERG after inducing 30-, 60-
      and 90-minute ischemia. A ganzfeld dome was utilized to stimulate both the
      experimental and the control fellow eye. The changes in ERG parameters in the
      ischemic eye were assessed by comparison with the values simultaneously obtained
      in the fellow eye, which could minimize the effect of anesthesia. One hour after
      reperfusion, the implicit time returned to almost the same value as that in the
      fellow eye in eyes with 30-minute ischemia, while it showed significant delay in
      eyes with 60-minute ischemia. The amplitude was smaller than that in the fellow
      eye in eyes with both 30- and 60-minute ischemia. Photopic ERG was not recorded
      one hour after reperfusion in more than half the eyes with 90-minute ischemia.

PMID- 8577077
TI  - Quantitative analysis of electromyogram interference pattern in extraocular
      muscle.
AB  - Turns and amplitude analysis of the electromyogram (EMG) interference pattern has
      been applied to the extraocular muscles for the first time in the literature, to
      the best of our knowledge. EMGs of 261 horizontal rectus muscles recorded during
      the past 18 years were retrospectively examined and divided into four categories
      according to the clinical diagnosis: 56 complete palsy due to neuropathy, 67
      incomplete palsy due to neuropathy, 19 myopathy, and 119 normal. The number of
      turns per second and mean amplitude between a pair of successive turns were
      automatically calculated by computer. Significant differences (P < 0.05) were
      encountered in all data among the four clinical categories except for the number
      of turns between myopathy and normal. The number of turns was plotted against the
      amplitude in each muscle on an X-Y diagram. The data of completely paretic muscle
      showed less number of turns and smaller amplitude and were clearly
      distinguishable from the data of the other three categories on the X-Y diagram.
      The interference pattern of incomplete palsy and myopathy had smaller amplitude
      than that of normal muscle. However, most of the data overlapped on the X-Y
      diagram particularly between data of incomplete neuropathy and myopathy.

PMID- 8577078
TI  - Current trends in cataract and refractive surgery in Japan--1994 survey.
AB  - A third annual survey was carried out by mail in January 1995 to investigate the
      current trends in cataract and refractive surgery in Japan. A questionnaire was
      sent to 837 ophthalmologist among members of the Japanese Society of Cataract and
      Refractive Surgery. Data received from 48.5% of the recipients were cross
      analyzed and compared with those from the previous surveys.

PMID- 8577079
TI  - Visual field damage proximal to fixation in normal- and high-tension glaucoma
      eyes.
AB  - To compare in more detail the central visual field damage in normal-tension
      glaucoma (NTG) and high-tension glaucoma (HTG) eyes, a pointwise inner-group
      comparison of the data obtained with the Humphrey 10-2 was carried out in 68 NTG
      cases with maximum intraocular pressure (IOP) of < or = 21 mmHg and 62 HTG cases
      with maximum IOP of > or = 25 mmHg. All eyes had the usual field defects, with a
      mean deviation of > or = -15 dB (MD, STATPAC). Age, refraction and MD were
      matched between the two groups. Total deviation (TD, STATPAC), the difference
      between the measured threshold and the age-corrected normal reference at each
      test point of the 10-2 program, was used for pointwise inter-group comparisons.
      The data were analyzed with Wilcoxon rank-sum test and logistic discriminant
      analysis. The latter method was also applied to the data of the 30-2 program to
      confirm the results obtained with the 10-2 program. The comparisons using the
      different methods and programs gave consistent results. For a given amount of
      overall visual field damage in the two types of glaucoma, a superior arcuate area
      extending down to the horizontal meridian just nasal to the fixation point was
      significantly more depressed and an area inferior to the horizontal meridian and
      inferior temporal to the fixation point significantly less depressed in NTG eyes.
      HTG eyes were significantly more diffusely damaged in the central 10-degree
      visual field. NTG and HTG may have unique patterns of central visual field
      damage. These differences may implications in following NTG patients and studying
      the pathogenesis of this glaucoma.

PMID- 8577080
TI  - Ocular findings in a patient with Prader-Willi syndrome.
AB  - A 25-year-old woman is described whose clinical features included infantile
      hypotonia, obesity after infancy, intellectual impairment, dysmorphic facial
      features, short stature, small hands and feet, and abnormal dentition, which are
      typical of the Prader-Willi syndrome. The patient had almond-shaped eyes, spot
      like hypopigmentation under the retina, and a polychromatic luster in the
      anterior and posterior subcapsular regions of both lenses. Using fluorescence
      fundus angiography, we identified choroid-transmitted fluorescence in the areas
      of spot-like hypopigmentation. Recordings of both electroretinogram and visual
      evoked potential were normal. Ophthalmologists should be aware of the
      characteristic features of Prader-Willi syndrome because some of the ocular
      disorders associated with this syndrome can be treated.

PMID- 8577081
TI  - Visual function in patients with optic neuritis associated with acute transverse
      myelopathy in multiple sclerosis.
AB  - The authors reviewed the records of 20 patients with optic neuritis, all of whom
      were diagnosed as having clinically definite multiple sclerosis (MS). They were
      classified into two subgroups: Group A, consisting of 9 patients who had shown
      acute transverse myelopathy (ATM); and Group B, 11 patients without ATM. Four
      patients (44%) in Group A had complete visual loss, but none in Group B. Six
      patients (67%) in Group A had less than 0.1 visual acuity in the affected eye,
      but only 2 patients (18%) in Group B. Four patients in Group A showed evidence of
      anticardiolipin antibodies. While both groups were diagnosed as having clinically
      definite MS, there were differences between them in the clinical features. We
      assume that the patients with ATM may constitute a different subgroup among MS
      patients.

PMID- 8577082
TI  - The primary treatment of traumatic lesions of the orbital roof.
AB  - The possible treatments for dislocated fractures of the orbital roof range from
      reduction of the fracture fragments, and reconstruction and stabilisation with
      miniplates, to plastic surgery using autologous bone. Between 1988 and 1994, 105
      patients treated in the Department of Neurosurgery of the Landesnervenklinik
      Salzburg were operated on transcranially for fractures of the orbital roof. The
      methods of treatment, the timing of treatment, and the results are discussed. It
      is shown that even in severely injured patients the results were good in 83
      patients (79%).

PMID- 8577083
TI  - Functional magnetic resonance imaging of the primary visual cortex: evaluation of
      human afferent visual system.
AB  - The authors evaluated signal changes in the human primary visual cortex during
      visual stimulation using functional magnetic resonance imaging (MRI) scanner at
      1.5 Tesla. Experiments were performed on 10 normal volunteers and 2 patients with
      homonymous hemianopsia. In the normal volunteers, a signal increase was observed
      on the bilateral primary visual cortex during hemifield stimulation. In one
      patient with homonymous hemianopsia after cerebral infarction, the signal change
      was clearly decreased on the affected side. In the other patient, who was
      recovering from multiple sclerosis to an almost normal visual field, the fMRI
      results were within normal limits. These results suggest that it is possible to
      map noninvasively the activation of the visual stimulation with a clinical MRI
      system, and that this test might be useful as an objective method of visual field
      examination.

PMID- 8577084
TI  - Behcets disease in children.
AB  - Ophthalmic and clinical analysis were carried out on 16 children and 122 adult
      patients affected by Behcet's disease (BD) to delineate the clinical features of
      BD in childhood and to investigate the differences between the expression of the
      disease in children and adults. The mean follow-up period was 7.8 and 7 years,
      respectively. Pediatric onset of BD was found in 7.6% of all the cases with a
      male:female ratio of 1.29:1. The complete type of the disease was observed in 50%
      of the children. No statistical significant differences were noted between
      children and adults in the incidence of oral aphthae, genital ulcers, skin
      lesions, arthritis, gastrointestinal involvement, neuropsychiatric symptoms and
      the presence of HLA-B51. Thrombophlebitis was associated with the onset of the
      disease in adult age (P=0.022). Uveitis alone or in combination with other major
      symptoms was the presenting sign in a higher percentage of children (P=0.077), As
      in adults, in children diffuse uveitis was the most common type of ocular
      inflammation, while ocular complications have been found mainly in children
      (P=0.021), who more frequently developed cataract, maculopathy and retinal
      detachment (P=0.024). Both adult and young male patients have shown a lower age
      at onset and higher rate of optic atrophy than females. In conclusion, no
      significant differences have been found between children and adults in the
      expression of the major and most of the minor symptoms of BD. Ocular involvement
      in childhood may be very severe, as was confirmed by the high frequency of
      diffuse uveitis and ocular complications. Young males, as adult males, showed an
      earlier onset of the disease and a worse ocular prognosis.

PMID- 8577085
TI  - A novel system for small bowel preservation--cavitary two-layer (University of
      Wisconsin solution/perfluorochemical) cold storage method.
AB  - Organ preservation is very important to accomplish successful organ
      transplantation. Unlike the kidney, liver, pancreas or heart, the preservation
      method of the small bowel has not been established yet. In this study, we tested
      24-48hr-preservation of rat small bowel by a cavitary two-layer (University of
      Wisconsin solution (UW)/perfluorochemical (PFC)) cold storage method (two-layer
      method (group 1)) in heterotopic rat segmental small bowel transplant model, and
      compared it with simple cold storage method in UW (group 3). In an attempt to
      clarify that the oxygenation of the graft by the two-layer method allows for 48hr
      preservation, a cavitary two-layer method without oxygen bubbling (group 2) was
      also examined. The 7 day survival rates after 24hr-preservation were 100%, 67%
      and 86% for group 1, 2 and 3, respectively. On the other hand, the 7 day survival
      rates for group 1, 2 and 3 after 48hr-preservation were 86%, 20% and 0%,
      respectively. Histological studies of grafts preserved by the two-layer method
      (group 1) for 48hrs on the 7th day posttransplant showed almost normal
      architecture of the intestinal mucosa. This study demonstrated that the
      oxygenation of the small bowel during preservation by the cavitary two-layer
      method using UW allows for 48hr-preservation of rat small bowel. This method is
      simple and reliable and holds promise for clinical small bowel transplantation.

PMID- 8577086
TI  - The mechanism of action of the two-layer cold storage method in canine pancreas
      preservation--protection of pancreatic microvascular endothelium.
AB  - We have demonstrated that oxygenation of a pancreas during preservation by a two
      layer method leads continued ATP production to maintain cellular integrity and
      produces an extended period of preserved pancreatic viability. The aim of this
      study is to examine the effect of ATP vs. oxygenation per se on viability of
      nonparenchymal cell (vascular endothelium), using 2.4 dinitrophenol, an uncoupler
      of mitochondrial oxidative phosphorylation. Mongrel dogs of both sexes, weighing
      12-18kg were used. Under general anesthesia, a left lobectomy of the pancreas was
      performed. The segmental pancreas graft was autotransplanted immediately (group
      1; control) or after 48-hour preservation (group 2; simple cold storage method
      with Euro-Collins' solution [EC], group 3; two-layer cold storage method using
      EC, group 4; two-layer cold storage method using EC with 0.2 mM DNP), and the
      remainder of the pancreas was excised at the time of autotransplantation. Graft
      viability was judged from graft survival after transplantation. A K-value of
      intravenous glucose tolerance test more than 1.0 at 2 weeks after transplantation
      was considered graft survival. Tissue concentration of ATP was determined after
      preservation using high-performance liquid chromatography. Viability of vascular
      endothelium was examined using trypan-blue perfusion/fixation test after
      preservation. Nuclear staining by trypan blue in eosin-counterstaining sections
      was indicative of loss of cell viability. Pancreatic tissue perfusions, which
      reflect pancreatic microcirculation, were also measured using H2 clearance
      technique after 30 to 240 min of reperfusion. Graft survival rates in groups 1,
      2, 3 and 4 were 5/5, 0/4, 4/4 and 0/3 respectively. ATP tissue concentration was
      significantly higher in group 3 compared with group 2 (7.91 +/- 1.21 [n = 4] vs.
      1.21 +/- 0.31 [n = 4] mumol/g dry weight, p < 0.01). DNP caused a significant
      decrease in tissue ATP in group 4 (0.61 +/- 0.07 [n = 3] vs. 7.91 +/- 1.21 [n =
      4] mumol/g dry weight, p < 0.01). The percentage of nuclear trypan blue uptake of
      nonparenchymal cells in group 3 was significantly lower than group 2 (11.29 +/-
      3.71 [n = 3] vs. 26.41 +/- 1.66 [n = 3] %, p < 0.01), and DNP (group 4) increased
      trypan blue uptake (30.10 +/- 4.08 [n = 3] vs. 11.29 +/- 3.71 [n = 3] %, p <
      0.01). Tissue perfusions after 2hr-reperfusion in group 3 were significantly
      higher than group 2 (68.64 +/- 8.62 [n = 5] vs. 45.56 +/- 12.84 [n = 5]
      ml/min/100g, p < 0.01). Moreover, DNP (group 4) caused a significant decrease in
      pancreatic tissue perfusions (28.84 +/- 9.09 [n = 5] vs. 68.64 +/- 8.62 [n = 5]
      ml/min/100g. p < 0.001). It was clear that the two-layer method (group 3)
      protected microvascular endothelium against cold ischemic damage and inhibition
      of ATP production using DNP (group 4) caused endothelial damage, microcirculatory
      disturbance after reperfusion and consequently loss of graft viability. We
      conclude that microvascular endothelium of the pancreas graft is protected
      against cold ischemic injury by maintaining ATP tissue levels during preservation
      by the two-layer method. This is one of the mechanisms of action of the two-layer
      method in successful pancreas preservation.

PMID- 8577087
TI  - Follow-up observation of a patient with left ventricular thrombus by
      echocardiography.
AB  - We report a case of left ventricular thrombus which caused systemic embolism
      during warfarin therapy. A 66-year-old man admitted to our hospital with
      intermittent loss of consciousness and incomplete palsy. The patient had a past
      history of cerebral infarction, hypertension and diabetes mellitus.
      Electrocardiography showed abnormal Q waves at II, III, and aVF. Echocardiography
      showed a mobile protruding thrombus at the left ventricular apex. Left
      ventricular cineangiography showed a filling defect at the left ventricle.
      Coronary angiography confirmed total occlusion of the right coronary artery and
      significant stenosis of the left coronary artery. After administration of
      warfarin, the patient suddenly fell down to the comatose state. His left arm
      became pale without pulsation. The thrombus in the left ventricle disappeared by
      echocardiography and systemic embolism was suspected. Thromboembolectomy from his
      left arm was performed. Two weeks after the day brain computed tomography showed
      low density area at the posterior lobe of the cerebrum. Although the eyesight of
      the patient was lost, he could stand and walk with some help two months later.
      This is a rare case of systemic embolism during warfarin therapy due to left
      ventricular thrombus whose process was constantly observed by echocardiography.

PMID- 8577088
TI  - Classification of congenital hypothyroidism based on scintigraphy,
      ultrasonography and the serum thyroglobulin level.
AB  - In the present study, infants with congenital hypothyroidism discovered on
      neonatal mass screening were examined in order to clarify the pathogenesis by
      means of I-123 or Tc-99m scintigraphy, with and without thyroid ultrasonography
      and serum thyroglobulin measurement. The patients were divided into two groups:
      sixteen neonates with hypothyroidism discovered in a neonatal mass screening
      program performed between 1985 and 1992 (group A), and eleven neonates discovered
      between 1992 and 1994 (group B). In group A, only I-123 scintigraphy was
      performed to determine the pathogenesis. Group B was subjected to Tc-99m
      scintigraphy, thyroid ultrasonography and serum thyroglobulin measurement. The
      pathogenesis of thirteen patients with congenital hypothyroidism in group A (1985
      1992) were as follows; seven patients were diagnosed as having dysorganogenesis,
      consisting of six with ectopic glands and one with agenesis of the thyroid gland.
      Six patients were diagnosed as having dyshormonogenesis. All three patients with
      transient hypothyroidism were diagnosed as having transient dyshormonogenesis.
      The pathogenesis of eight patients with congenital hypothyroidism in group B
      (1992-1994) were as follows; one patient of dysorganogenesis with ectopic gland
      and seven patients of dyshormonogenesis consisting of one patient with iodine
      transport defect, one patient with iodine transport defect combined with ectopic
      gland, one patient with dyshormonogenesis combined with dysorganogenesis and four
      patients with only dyshormonogenesis. All of three patients with transient
      hypothyroidisms were diagnosed as transient dyshormonogenesis. These results
      suggest that the examination of thyroid scintigraphy and ultrasonography as well
      as serum thyroglobulin measurement are useful to clarify the etiology and
      pathogenesis of congenital hypothyroidism.

PMID- 8577089
TI  - [Military field surgery during World War II 1941-1945].

PMID- 8577090
TI  - [A case of a malignant kidney tumor with the nephrogenic liver dysfunction
      syndrome].

PMID- 8577091
TI  - [Lead gout].

PMID- 8577092
TI  - [A case of the successful treatment of true scleroderma kidney].

PMID- 8577093
TI  - [Wegener's granulomatosis with rapidly progressing glomerulonephritis
      successfully treated with immunodepressants].

PMID- 8577094
TI  - [Multifocal fibrosis].

PMID- 8577095
TI  - [Periarteritis nodosa with ruptures of the renal vessels and the persistence of
      the hepatitis B and C viruses in the blood].

PMID- 8577096
TI  - [Neurological care during World War II 1941-1945].

PMID- 8577097
TI  - [Pathological changes of the internal organs in injuries to earthquake victims].

PMID- 8577098
TI  - [The etiology of Leningrad blockade-related hypertension].

PMID- 8577099
TI  - [Fatigue and overfatigue].

PMID- 8577100
TI  - [Systemic arterial hypertension in chronic bronchial obstruction: current views
      and new understandings].

PMID- 8577101
TI  - [The involvement of the locomotor system in Lyme borreliosis].

PMID- 8577103
TI  - [Visceral pathology in peritonitis].
AB  - Visceral involvement was investigated in 168 patients with general peritonitis.
      Toxic hepatitis, toxic nephropathy, myocardia dystrophy, pulmonary impairment
      were determined in 85.7%, 83.3%, 69.6% and 19% of them, respectively. 44 (26.2%)
      patients with terminal peritonitis developed polyorganic insufficiency. Principal
      approaches to management of visceral pathology in peritonitis are analyzed.

PMID- 8577102
TI  - [The pathogenesis of thermal inhalation injury in burn patients].

PMID- 8577105
TI  - [Internal and military medicine in World War II 1941-1945].

PMID- 8577104
TI  - [The use of magnetic hemotherapy in combined detoxification in acute exogenous
      poisonings].
AB  - An original technique of magnetic hemotherapy has been tried in 110 patients with
      severe exogenic poisoning. The addition of the above hemotherapy raised the
      efficacy of combined detoxication due to correction of hemorheological and
      stabilization of hemodynamic parameters as indicated by diminished endotoxicosis,
      reduced lethality, prevention of somatic complications which when available
      became less severe.

PMID- 8577106
TI  - [The pathogenesis of a broncho-obstructive syndrome in patients with chronic
      bronchitis].
AB  - Lipid peroxidation (LPO) and antioxidant system (AOS) were investigated in 40
      patients with chronic obstructive bronchitis (COB) in relation to clinical
      features of the disease. Bronchial tree inflammation was associated with reduced
      AOS function and intensification of LPO which reached a new high level. LPO
      activity, tocopherol concentration in red cell membranes and the severity of
      respiratory obstructive syndrome were correlated. It is suggested that high LPO
      activity may underlie the disease chronicity and development of progressive
      irreversible bronchial obstruction. Antioxidant drugs are believed necessary for
      COB patients not only in acute, but also in regression and remission phases of
      the disease.

PMID- 8577108
TI  - [The antibiotic therapy of patients with hemorrhagic fever with renal syndrome].
AB  - Whether preventive antibiotics are beneficial in hemorrhagic fever with renal
      syndrome was checked up by the evidence obtained from 303 relevant case
      histories. The analysis showed undesirability of antibiotics, as they promote
      emergence of nonspecific complications and prolong the patients' stay in
      hospital.

PMID- 8577107
TI  - [The clinical picture of mycotic complications in HIV-infected patients].
AB  - Mycotic complications were registered in 21 out of 37 HIV-infected subjects.
      Oropharyngeal candidiasis was most common. It occurred prior to or concurrently
      with esophageal and skin candidiasis, fungemia, meningoencephalitis and
      disseminated lesions. With immunodeficiency progression, the prevalence and
      severity of mycosis go up. The causing fungi vary in great range: Candida
      albicans, Candida krusei. Candida tropicalis, Candida pseudotropicalis, Candida
      parapsilosis. Cryptococcus neoformans, Rhodotorula rubra, Penicillium
      chrysogenum.

PMID- 8577109
TI  - [The clinical efficacy of the first Russian angiotensin-converting enzyme
      inhibitor methiopril in patients with heart failure].
AB  - Changes in central hemodynamics as recorded by tetrapolar rheography were
      investigated in 90 coronary heart disease (CHD) patients with circulatory
      insufficiency (CI) receiving methiopril. Relevant clinical response was
      registered in 94%, hemodynamic in 83% of patients. Those with CI stage IIA and
      IIB benefited more. Arterial pressure went down significantly only in CHD
      patients with arterial hypertension. Tachycardia patients showed a reduction in
      pulse rate absent in bradycardia. Cardiac output increased at the expense of low
      afterload. Efficient doses averaged 300 mg/day.

PMID- 8577110
TI  - [The efficacy of gastrotsepin in functional diseases of the large intestine].

PMID- 8577111
TI  - [Errors in the diagnosis of anthrax].

PMID- 8577112
TI  - [A trichinelliasis outbreak in Samara Province].

PMID- 8577113
TI  - [Pollinosis and arterial hypertension].

PMID- 8577114
TI  - [A case of an atypical course in complicated intestinal yersiniosis].

PMID- 8577115
TI  - [2 cases of brain tumors with the primary manifestations as endocrine functional
      disorders].

PMID- 8577116
TI  - [The early diagnosis and differential diagnosis of pulmonary tuberculosis].

PMID- 8577117
TI  - [Heart sound phenomena in the diagnosis of congenital heart defects].

PMID- 8577118
TI  - [The surgical procedure in acute suppurative pyelonephritis].

PMID- 8577120
TI  - [Evgenii Mikhailovich Tareev. On the centenary of his birth].

PMID- 8577119
TI  - [The contribution of B. E. Votchal to the Russian school of internal diseases (on
      the centenary of his birth)].

PMID- 8577121
TI  - [Kidney involvement in multiple myeloma].

PMID- 8577122
TI  - [The clinico-morphological characteristics of interstitial lung diseases].
AB  - Electron microscopic and immunohistochemical methods were employed to study
      composition of collagens in extracellular matrix and quantify oncoproteins c-sis
      and c-fos. It was established that interstitial pulmonary diseases of various
      etiology are characterized at early stages by alveolitis with activation of
      alveolar macrophages, at late stages by interstitial fibrosis with accumulation
      of collagens type I, III, IV and V and epithelial dysplasia which is likely to
      initiate bronchioloalveolar cancer.

PMID- 8577123
TI  - [Means for the inhibition of the nonimmune progression of nephritis].
AB  - Inhibition of non-immune progression of renal insufficiency for control of
      glomerulonephritis was attempted via hemodynamic, metabolic and hypolipidemic
      means. Hemodynamic correction was conducted using inhibitors of angiotensin
      converting enzyme capoten and renitek. The action on metabolic factors of
      progression was realized by lovastatin mevakor. Capoten and renitek exhibited in
      57 patients with chronic nephritis not only a hypotensive effect, but also
      reduced intraglomerular hypertension and proteinuria. A long-term (7-12 months)
      hypolipidemic therapy (diet and lovastatin) in 20 patients with chronic
      glomerulonephritis with nephrotic syndrome resulted in lowering of serum
      cholesterol concentrations and proteinuria, raised serum albumin. 9 patients
      achieved remission of nephrotic syndrome. The highest effect occurred in non
      inflammatory nephropathy: membranous nephropathy, focal-segmental
      glomerulosclerosis, nephrosclerosis.

PMID- 8577124
TI  - [The results of the nephrological examination of women with a history of
      nephropathy in pregnancy].

PMID- 8577125
TI  - [A clinical trial of a new method for treating chronic nephritis with superhigh
      doses of cyclophosphane].

PMID- 8577126
TI  - [Acute kidney failure in patients with glomerulonephritis related to the use of
      furosemide].
AB  - An analysis was made in 22 patients with glomerulonephritis taking furosemide as
      to occurrence of acute renal failure. The authors infer that furosemide
      administration is not fully safe and the physician should be careful not to
      initiate hypovolemia and azotemia.

PMID- 8577127
TI  - [The characteristics of kidney involvement in a female patient with systemic
      lupus erythematosus and the antiphospholipid syndrome].
AB  - A case of rapidly progressive nephritis is reported in a female patient having
      systemic lupus erythematosus (SLE) with antiphospholipid syndrome. Clinical
      presentation of progressive lupus nephritis with intensifying renal
      insufficiency, arterial hypertension, hematuria, nephrotic syndrome was
      associated with unusual morphological manifestations of mesangiocapillary
      glomerulonephritis with advanced vasculitis. The authors attribute a malignant
      nephritis course atypical for patients with antiphospholipid syndrome to
      development of renal vasculitis. The discussion covers lupus genesis of vascular
      involvement, a probable triggering role of antibodies to phospholipids in
      impairment of endothelial cells.

PMID- 8577128
TI  - [The procedure for using Renitec (an angiotensin-converting enzyme inhibitor) for
      the treatment and prevention of diabetic nephropathy].

PMID- 8577129
TI  - [The clinical significance of renal functional reserve].
AB  - Patients at risk to develop intraglomerular hypertension were denoted among those
      with chronic glomerulonephritis (CGN) basing on the relationships between various
      clinico-laboratory findings, clinical syndromes and markers of intraglomerular
      hypertension (low or absent renal functional reserve). The risk groups include
      CGN patients with urinary syndrome and arterial hypertension with nephrotic
      disease and serum creatinine over 1.4 mg/%, with renal damage typical for focal
      segmental glomerulosclerosis or fibroplastic glomerulonephritis. Patients with
      nonimmune progression via a rise of intraglomerular pressure should be given
      drugs reducing intraglomerular hypertension.

PMID- 8577130
TI  - [Glycemia as a risk factor of reduced tolerance of hypoxic hypoxia in flight
      personnel].
AB  - The glycemic level was measured in 61 people exposed to hypoxic hypoxia. Three
      major types of glycemic responses were identified: type I--no change (15.79%);
      type II--hypoglycemia (49.12%), and type III--hyperglycemia (35.09%). The
      subjects with a low resistance to hypoxic hypoxia typically showed a low glycemic
      level (57.5 +/- 2.5 mg%. P < 0.05). It is suggested that three types of glycemic
      responses to hypoxia reflect three major pathways of biochemical adaptation of
      the body. It is recommended to study hormonal changes in people with
      hyperglycemic responses to hypoxia. This will help determine hormonal levels
      responsible for hyperglycemia and, consequently, develop methods of early
      detection of susceptibility to cardiovascular diseases and diabetes mellitus.
      This approach may contribute to medical expertise and rehabilitation of the
      flying personnel.

PMID- 8577131
TI  - [Changes in the structure of erythrocyte membrane and Na+. K+-ATPase activity in
      participants of the Soviet-Canadian trans-Arctic ski pass].
AB  - Changes in the structure of erythrocyte membranes and kinetics of the membrane
      bound enzyme Na+, K(+)-ATPase were measured in members of the Canadian-Soviet
      transarctic ski pass that took place in March-May 1988. Hemoglobin content
      decreased at the Pole (by 22%) and partially recovered in Canada; phospholipids
      in erythrocyte membranes diminished at the Pole and in Canada (by 30%). During
      the pass water concentrations in membrane proteins and phospholipids increased
      significantly. Changes were found in rheological properties of membranes, e.g.,
      viscosity of erythrocyte shadow suspensions at critical temperature (Tc) which is
      within the physiological range (36-38 degrees C) and viscosity in the temperature
      range 34-42 degrees C. Electric conductivity varied as a function of temperature
      (delta sigma(T)]. At 36-38 degrees C sigma showed abnormal variations. The
      integral intensity of IR-spectra of absorption bands of COp (peptide bonds) and P
      O-C (phospholipids) decreased and the half-width of the COp absorption band
      increased during the pass. The activity of Na+, K(+)-ATPase of erythrocyte
      shadows diminished which was in correlation with membrane structure changes. The
      temperature optimum of Na(+)-, K(+)-ATPase occurred at 37-38 degrees C and
      coincided with the region of the structural phase transition detected by the
      authors.

PMID- 8577132
TI  - [Functional properties of blood proteins in highly trained athletes].
AB  - The functional properties of serum albumin and hemoglobin were investigated in
      highly trained athletes. During adaptation to regular strenuous exercise, the
      metabolic pathway of omega 3 fatty acids intensified and the content of lipid
      peroxidation products in serum albumin increased. Also, hemoglobin affinity for
      molecular oxygen decreased and ATP concentration in red blood cells increased.

PMID- 8577133
TI  - [Effects of different pathologies of the cupula-endolymphatic system of the
      vestibular apparatus on its dynamic characteristics].

PMID- 8577135
TI  - [Effect of weightlessness on the course of the reparative process in the muscles
      of the biosatellite Kosmos-2044 rats].
AB  - The repair process in the soleus and gastrocnemius muscles of SPF Wistar rats
      flown for 14 days on the biosatellite Cosmos-2044 was investigated. The muscles
      were injured 2 days before launch by means of clamp forceps. The exposure
      inhibited the process but did not impair its phasic development. As a result, the
      reparative field diminished and took the size of an atrophic muscle; thinner
      myofibers appeared that originated from the ends of injured atrophic fibers and
      fibers that underwent splitting. It is postulated that repair inhibition is
      caused by the same mechanisms that produce muscle atrophy in microgravity. It is
      suggested that both repair inhibition and muscle atrophy are induced by disorders
      in the neurotrophic regulation of metabolism due to partial disuse.

PMID- 8577134
TI  - [Role of external respiration in the formation of the autonomic component in
      motion sickness].
AB  - Time course variations in the ventilation and gas exchange functions of the
      lungs, gas composition and acid-base equilibrium of blood were investigated in 22
      male test subjects, aged 27-49 years, who were kept in the head-down position (-8
      degrees) and rocked in parallel swings. The subjects susceptible to motion
      sickness developed lung hyperventilation and concomitant alveolar-arterial
      hypocapnia and respiratory alkalosis which may potentiate a symptom-complex of
      vestibular disorders. To control hypocapnia, the subjects used a hypercapnic
      breathing mixture (4% CO2, 96% air). This eliminated the above changes in the gas
      composition and acid-base equilibrium of blood, and in 7 out of 10 subjects
      alleviated vestibular symptoms and elongated the time of motion tolerance. In
      addition, the prophylactic effect of hypercapnic exposure showed individual
      variations which seem to be associated with individual sensitivity of the
      respiratory center to hypercapnic stimulation.

PMID- 8577136
TI  - [The effect of weightlessness on fracture healing of rats flown on the
      biosatellite Cosmos-2044].
AB  - Two days before launch of the biosatellite Cosmos-2044 five rats were exposed to
      surgical intervention: their fibulas were cut bilaterally. The purpose was to
      study the effect of microgravity on bone fracture healing. Histologically and
      histomorphometrically it was demonstrated that healing was inhibited; as a
      result, bone callus was poorly developed and bone fragment consolidation was
      inadequate. An increase in the relative volume of osteoid and a simultaneous
      decrease in the number and activity of osteoblasts point to mineral disorders of
      newly formed bone in microgravity. Study of untreated tibia showed that exposure
      to microgravity led to osteoporosis of proximal metaphyses. This osteoporosis was
      produced by inhibited neoformation and enhanced resorption of bone. Comparative
      analysis of injured fibula and untreated tibia of rats exposed to real
      microgravity for 14 days or tail suspended demonstrated similarity of changes.
      This indicates that tail suspension can be viewed as an adequate simulation of
      microgravity with respect to changes in hindlimb bones.

PMID- 8577137
TI  - [Dynamics of prostaglandin contents and several indicators of lipid metabolism in
      man exposed to prolonged hypokinesis].
AB  - Nine healthy test subjects divided into Group A and Group B were bed rested (with
      the head down at -5 degrees) for 370 days. Group A subjects exercised from the
      beginning of the study while Group B subjects began exercising only 120 days
      after. During the study prostaglandins PGE and PGF2 alpha in serum and fatty
      acids in serum and erythrocyte membranes were measured. The lipid concentration
      in erythrocyte membranes decreased during the study and returned to the norm at a
      final stage and after the study. However, changes in higher fatty acids and a
      dramatic decline of prostaglandin give evidence for serious alterations of lipid
      metabolism at the cellular level.

PMID- 8577138
TI  - [Calcium pooling by plasma and extra-plasma buffer systems: effects of prolonged
      hypokinesia].
AB  - Healthy test subjects were intravenously injected with calcium solutions during
      ambulatory activity and after 100-day exposure to head-down tilt. It was
      demonstrated that different mechanisms were involved in maintaining ionized
      calcium at a constant level and that their contribution changed after the tilt
      study. It was also shown that the capacity of extra plasma pool was decreased,
      kinetic characteristics of the Ca2+ binding reaction were modified, and responses
      of mineralotropic hormones to induced hypercalcemia were enhanced.

PMID- 8577139
TI  - [Tolerance of chest-to-back [+Gx] and head-to-feet [+Gx] acceleration in drug
      induced hypohydration].
AB  - The effect of drug-induced hypohydration (furosemide, 40 mg per os) on the
      tolerance of chest-to-back (+Gx) and head-to-feet (+Gz) acceleration was
      investigated in 9 healthy male test subjects, aged 25-45 years. The test subjects
      were rotated in a 7.5 m arm centrifuge. The first exposure during which they were
      centrifuged at 4 G (+Gx and +Gz) served as a control. The second time they were
      exposed to centrifugation after diuretic administration. Prior to second
      exposure, the subjects showed increased diuresis (5.7 +/- 0.7 ml/min) and
      increased excretion of osmotically active compounds, including electrolytes. This
      led to a decrease of the circulating blood volume by 7.0 +/- 1.8% on an average.
      During centrifugation the following parameters were recorded: electrocardiogram,
      blood pressure in the arm and ear lobe vessels, ear pulsogram, and pneumogram.
      After diuretic intake +Gx tolerance remained essentially unchanged whereas +Gz
      tolerance was good but required greater efforts. It is concluded that moderate
      diuretic-induced hypohydration did not result in a drastic deterioration of
      acceleration tolerance.

PMID- 8577141
TI  - [Value of several hormone indicators and cyclic nucleotides in the assessment and
      prognosis of resistance to acute hypoxia during operator activities].
AB  - A study was performed in which 16 healthy volunteers, aged 25-40 years, worked in
      a two-dimensional tracking simulator and breathed a mixture containing 9-12%
      oxygen. This led to a higher incretion of cortisol, insulin, somatotropin, a
      greater renal excretion of epinephrine, norepinephrine, and a higher content of
      cAMP in lymphocytes, plasma and urine. The subjects with a higher insulin in
      plasma and renal excretion of catecholamines showed a longer time of tolerance to
      the above exposure which varied from 50 to 120 min. The high tolerance was
      combined with a greater activity of the sympathoadrenal system, incretion of
      cortisol and cAMP in lymphocytes. A significant correlation was demonstrated
      between cAMP in the above environments both before and after exposure.

PMID- 8577140
TI  - [Several indicators of protein and nucleic acid metabolism in lymphoid organs of
      rats exposed to hypokinesia and vitamin B1 deficiency].
AB  - RNA, DNA, total protein, transketolase (TK), alanine aminotransferase (AlAT),
      aspartate aminotransferase (AsAT), methionyl-tRNA (met-tRNA)- and cysteinyl-tRNA
      (cys-tRNA)-synthetases in the thymus and spleen of 46 intact rats exposed to
      hypokinesia and vitamin B1 deficiency were measured. It was found that 15-day
      hypokinesia induced a significant decrease of the thymus and spleen weight and an
      increase of AlAT in the thymus. Vitamin B1 deficiency (hydroxy thiamine in
      drinking water at a dose of 2 mg/kg body weight for 15 days) led to a substantial
      decrease of TK in blood, AlAT and AsAT in the spleen; it diminished AsAT and
      increased AlAT in the thymus. Combined exposure to hypokinesia and vitamin B1
      deficiency caused a more marked decrease of the weight of lymph organs, a
      significant loss of body weight, an increase of DNA in the thymus and spleen, and
      an increase of TK, met-tRNA-synthetase and AlAT in the thymus. These results
      suggest that vitamin B1 deficiency aggravates disorders in protein and nucleic
      acid metabolism in the lymph organs of hypokinetic animals.

PMID- 8577142
TI  - [Functional state of the CNS in the early period of the development of radiation
      injury caused by helium ion irradiation].

PMID- 8577143
TI  - [Effects of isolated and combined effects of a constant magnetic field and
      antiorthostatic hypokinesia on central hemodynamics in rats].
AB  - The effect of a constant magnetic field on central circulation of rats was
      investigated during their exposure to antiorthostatic hypokinesia. Circulation
      parameters were measured by impedance rheoplethysmography. It was found that 3
      hour exposure to a 0.4 T magnetic field did not produce a significant effect on
      central circulation, whereas exposure to hypokinesia caused substantial changes
      which included decreases of heart rate, stroke volume and cardiac output. During
      a combined exposure to a constant magnetic field and antiorthostatic hypokinesia,
      the magnetic field exerted a beneficial effect on central circulation.

PMID- 8577144
TI  - [An experimental study on the effects of high pressure on adsorption properties
      of silochrome C-120].
AB  - Adsorption properties of silochrome in a helium atmosphere at 77 as were
      investigated. It was demonstrated that at a high pressure adsorption properties
      of silochrome changed and Henry coefficients decreased.

PMID- 8577145
TI  - [Effects of an impulse electromagnetic field on calcium ion accumulation in the
      sarcoplasmic reticulum of the rat myocardium].
AB  - By means of an ion-selective electrode, the effect of an impulse electromagnetic
      field with a 1 ms impulse, 10 Hz frequency, and 1-10 mT magnetic induction on
      calcium transport was investigated in the presence of potassium oxalate by rat
      heart homogenates. Prolonged exposure (100 min) to the field produced 70%
      inhibition of Ca2+ transfer across the sarcoplasmic reticulum. This effect is
      associated with direct inhibition of Ca(2+)-ATPase.

PMID- 8577146
TI  - [Study of cyclic kinetics of immunity by mathematical modeling methods].
AB  - The mathematical model of the dynamics of humoral immune responses to soluble
      antigens has been developed. This is a system of nonlinear differential equations
      describing concentrations of immunocompetent B-lymphocytes, plasma cells,
      antibodies and antigen. The model reproduces cyclic kinetics of the immune
      reaction to slowly catabolizing antigens which is observed experimentally. Within
      the framework of the model a description of the mechanism of origin of
      oscillatory modes of the dynamics of the immune response is presented. It has
      been shown that the feedback in the control of the antibody synthesis by
      antibodies is due to neutralization of the main stimulus of the immune system,
      i.e., free molecules of the antigen--by circulating antibodies.

PMID- 8577147
TI  - [Creation of new technology for conduction of controllable autonomous complex
      medical studies on board the MIR orbital station under the SHIPKA project].

PMID- 8577148
TI  - [Method of determination of calcium in the hand by 238-Pu-Be source neutron
      activation].

PMID- 8577149
TI  - [Response of regional vascular tone to orthostatic and gravitational effects].
AB  - The effect of active orthostasis and +Gz acceleration on regional vessels was
      investigated with the participation of 6 test subjects. Using
      photoplethysmography, the arterial pulse and venous blood filling of vessels of
      the finger at the level of the right atrium and at 41 cm above and below it were
      measured. This corresponded to variations of the intravascular hydrostatic
      pressure within the range +/- 30 mm Hg. This test was performed before and after
      exposure to acceleration of 5, 7, 8 and 9 G for 30 s at an onset rate of 1.0 G/s
      in the horizontal and vertical position. Arterial and venous responses were
      determined by comparing the results obtained at extreme levels of hydrostatic
      pressure. In all cases, increase in hydrostatic pressure led to enhancement of
      arterial tone and venous blood filling. After exposure to acceleration arterial
      tone and venous blood filling grew to a greater extent, particularly in the
      horizontal position. It is believed that the above method of measuring responses
      of regional vessels may prove useful to assess the vascular function after
      orthostatic, gravitational and other effects.

PMID- 8577150
TI  - [Structure of nocturnal sleep and susceptibility to motion sickness].

PMID- 8577151
TI  - [Prophylactic and sensitizing effects of biologically active substances in animal
      modeling of vestibular disorders].

PMID- 8577152
TI  - [Attempt at radiation protection during sublethal irradiation in hypergravity
      state].

PMID- 8577153
TI  - [Specific features of humoral immunity and nonspecific resistance in pilots].
AB  - Immune responses of the flying personnel to adverse flight effects were
      investigated. Altogether 134 pilots in the age of 22 to 42 years were examined. A
      significant decline of IgA, IgM, IgG, C3, alpha-antitrypsin, and R-proteins was
      found. Correlation analysis of over 100 anthropometric, psychophysiological,
      immune parameters as well as questionnaire data helped identify correlates and
      develop mathematical models which included IgA and IgM as parameters. Analysis
      shows that there is a relationship between personality features and humoral
      immunity of pilots: emotional strain increases, emotional stability decreases
      while immunoglobulins decline. In response to flight effects, changes in
      physiological functions, personality features, humoral immunity, and nonspecific
      resistance were interrelated.

PMID- 8577154
TI  - [Hematological parameters of cosmonauts during space flight].
AB  - This paper present hematological data obtained during space flights of the third
      and the fourth prime crew flights (EO-3 and EO-4). In the EO-3 flight, RBCs, WBCs
      and blood formed elements were counted by the cosmonaut-researcher. In the EO-4
      flight, blood was drawn by the cosmonaut-researcher and analyzed on the ground;
      also, blood smears treated in the Microview unit and videotaped were used. Blood
      parameters in EO-3 and EO-4 crewmembers were close or equal to the normal.
      However there were cases with changes in bends, myelocytes, neutrophils,
      lymphocytes; also anisocytosis, hypochromia, target-like erythrocytes, and single
      acanthocytes were seen. Comparison of blood smears on unstained and stained glass
      slides revealed significant differences in the amount of target-like erythrocytes
      in the same cosmonaut at the same time (on the prestained glass slide only 4
      erythrocytes and no aggregates in single fields of vision were detected while on
      the unstained glass slide aggregates in single fields of vision were seen). Pre-
      and postflight examinations of bone marrow revealed polymorphocellular marrow and
      mature hemopoietic cells.

PMID- 8577155
TI  - [Model of the perception of perturbed angular motion of the cockpit as part of
      pilot's information model].
AB  - This paper presents the method, algorithm and results of structural
      identification as a model of pilot's perception of perturbed angular motion of
      the cockpit and its transmission to the joystick as well as spectral density of
      the remnant corresponding to the transmission process. Assessments of scalar
      quasilinear and (more effective) multichannel models of pilot's functions are
      given. The assessments have been obtained for a single operator. They illustrate
      the potentials of this procedure.

PMID- 8577156
TI  - [Microbiological aspects of the environment of deep sea habitats].
AB  - It is known that the hyperbaric environment facilitates selection of gram
      negative microorganisms which acquire ecological predominance. From this point of
      view deep sea habitats can be regarded as a specific anthropotechnological niche
      for pathogenic microorganisms, particularly Pseudomonas aeruginosa A. aeruginosa
      colonization of the mucosa and skin of deep sea divers may result in infection
      manifestations which took place in chamber experiments when test subjects showed
      otitis externa and when virulent strains were isolated. It was demonstrated that
      the basic reservoir of P. aeruginosa was the water supply system. Hence,
      development of a reliable method for its disinfection should be of highest
      priority. One of the potential methods is SHF treatment. Another important
      approach is personal hygiene procedures preventing skin and mucosa contamination
      with potentially pathogenic microorganisms and procedures for increasing
      colonization resistance of divers with the aid of eubiotic therapy.

PMID- 8577157
TI  - [External respiration and gas exchange in man exposed to simulated diving at 350
      M].
AB  - Nine test subjects performed 4 dives in a He-O2 atmosphere at 3.5 MPa for 3-21
      days. Their external respiration and gas exchange were measured at rest and
      maximum physical load. At rest the basic respiratory parameters remained
      unaltered. However respiratory reserves decreased under the influence of
      increased gas density. At a maximum workload the power of which proved lowered
      the ventilation gain was inadequate. This led to CO2 retention in the body and,
      consequently, to subjects' refusal to continue physical work. Prolonged exposure
      to 3.5 MPa caused the most significant respiratory changes during the first 3
      days and their slight normalization and constancy during subsequent 2.5 weeks.
      This was, probably, associated with a slight pO2 increase in the breathing gas.

PMID- 8577158
TI  - [Development of decompression regimens for excursion dives after a prolonged
      exposure to 21 ata].
AB  - Decompression regimens for excursion dives from a depth of 20, 50, 100 or 200 m
      were developed and tested in a dry altitude chamber. Each dive continued for
      about 2 weeks, during which test subjects performed 10 excursion dives to a lower
      depth. No cases of decompression sickness were observed during 246 man/excursions
      whereas two cases of decompression sickness occurred in a field study.

PMID- 8577160
TI  - [Grooming and motor activity of rats during hyperbaric exposure].
AB  - An experiment was performed in which Wistar male rats were exposed to a N2-O2
      atmosphere at 10 kgf/sm2 or He-O2 atmosphere at 10 and 40 kgf/cm2. During the
      experiment grooming and motor activity as well as plasma corticosterone were
      investigated. Irrespective of the atmosphere composition, behavioural and
      biochemical parameters were found to increase significantly. At 10 kgf/cm2, the
      grooming frequency returned to normal faster than at a higher pressure. These
      observations give evidence for a nonspecific effect of the above hyperbaric
      factors on the parameters taken under study.

PMID- 8577159
TI  - [Metabolic changes during hyperbaric oxygenation].
AB  - Biochemical changes in response to a high partial pressure of oxygen were
      investigated in 12 test subjects. During exposure to compressed oxygen breathing
      (pO2-0.25 MPa) for a limited period of time changes in the carbohydrate, protein,
      enzyme, and electrolyte status were seen. These changes were demonstrative sings
      of physiological and toxic effects of oxygen. Individual metabolic responses were
      investigated and optimal exposure times were determined. It is recommended to
      take into consideration biochemical variations when identifying human resistance
      to oxygen toxicity on an individual basis.

PMID- 8577161
TI  - [Functional changes of the cardiovascular system and their pharmacological
      correction during suited immersion].
AB  - In the course of 126 man/exposures of 3 hours to 3 days in duration, in which 39
      test subjects took part, circulation responses to the upright and supine body
      position during suited immersion as well as orthostatic and exercise tolerance
      after immersion were investigated. During 24 man/exposures for 2 days the
      subjects were administered per os placebo or one of the four neurotrophic drugs:
      sydnocarb, sydnogluton, sydstrigluton, estrigluton. Clinical observations,
      instrumented data and methodical features of the immersion model used give
      evidence that the suited immersion has advantages over currently used procedures
      simulating the effects of hypogravity. The drugs allowed cardiovascular
      correction that increased aerobic capacity of the body and enhanced
      cardiovascular orthostatic and exercise tolerance.

PMID- 8577162
TI  - [Specific features of the motor function of the digestive organs in persons with
      different degree of resistance to motion sickness].
AB  - The effect of three exposures to Coriolis acceleration on the frequency and
      amplitude of fasting stomach contractions was investigated in 6 resistant and 16
      susceptible to motion sickness test subjects. After tests all of them underwent
      gastroduodenoscopy and 4 subjects from each group were subjected to echography to
      measure gall bladder contractility in response to glucose-milk loads. After tests
      the motor activity of the stomach increased slightly in resistant subjects due to
      an increase of the amplitude and a slight decrease of biopotential frequency.
      During gastroscopy antral and pyloric sphincters were closed. In the stomach
      there was an insignificant amount of contents without gall. In the susceptible
      group, the motor activity was, on the contrary, inhibited due to a significant
      decline of the wave amplitude and frequency (by 40% and 11%, respectively). In
      the stomach, one or both sphincters were widely open; it also contained a large
      amount of gastric juice and gall. In 36% of susceptible and 17% resistant
      subjects, diaphragmatic hernia (at the esophageal opening) was found. Ultrasonic
      examination of the gall bladder showed that susceptible subjects developed its
      faster and stronger contraction when compared to resistant subject in response to
      glucose-milk loading. This pointed to a more prolonged duration of the gall
      excretion phase. Reactive changes of the gastroduodenal zone in response to
      motion tests facilitated duodenal-gastric reflux and major gastrointestinal
      symptoms of motion sickness.

PMID- 8577163
TI  - [Nuclease activity of microorganisms and control of auto-microflora state of
      operators in hermetically sealed environment].
AB  - A study was performed to investigate biological properties of pathogenic
      microorganisms (Shigella, Salmonella, Staphylococcus aureus) and potentially
      pathogenic microorganisms which were isolated from different people, i.e.
      clinically healthy people with normal microflora, somatically healthy patients
      with intestinal dysbacteriosis, and patients with acute intestinal diseases. The
      most important parameters of pathogenicity typical of the basic representatives
      of pathogenic microflora were DNA and/or RNA forming activity. The "critical"
      size of depolymerization zones of nucleic acids on dense nutrient media was found
      to be equal to 2 mm and greater from the colony edge. The critical size was shown
      to be significantly different in potentially pathogenic and normal intestinal
      microorganisms. Maximal microbial concentrations in the major biotopes of man
      were estimated to be: no more than 25%, 5% and 2% for nasal mucosa, back skin,
      and for the large intestine of the total amount of microorganism in the test.
      Verification of the method gave evidence that in can be applied for an
      alternative evaluation of automicroflora of the large intestine of operators in
      an enclosed environment. It is suggested that the normal parameters
      characteristic of clinically healthy people need to be verified and applied in
      space and undersea medicine.

PMID- 8577164
TI  - [External respiration and gas exchange in space flights].
AB  - This is an overview of investigations performed in actual and simulated flights
      to study the effects of microgravity and acceleration, space cabin and space suit
      artificial atmosphere on the respiratory function. The conceptual prediction of
      the effects that the space environment produces on the respiratory system
      suggests the following changes in respiration, gas exchange, and acid-base
      equilibrium: respiration biomechanics; gas diffusion and ventilation-perfusion
      ratios in the lungs; regulation of respiration and function of respiratory
      muscles; lung hydration and blood filling; respiratory changes in acid-base
      equilibrium and blood gases. Besides, the combined effect of microgravity,
      acceleration, low barometric pressure and modified gas composition may cause lung
      atelectases and concomitant disorders in pulmonary ventilation and gas exchange.
      These changes may have an adverse effect on the health condition and physical
      work capacity.

PMID- 8577165
TI  - [Biocatalysis using immobilized cells or enzymes as a method of water and air
      purification in habitable enclosed environment].
AB  - This paper shows that the method of water and air purification using immobilized
      cells and enzymes can be applied in regenerative life support systems in a
      habitable enclosed environment. This method is based on selective and adaptive
      functions of enzymic systems of microorganisms to assimilate organic components
      of the medium to be eliminated. Advantages of biocatalysis are low energy
      requirements and mild temperatures of purification leading to practically
      complete elimination of the substrate. Due to immobilization, cells and enzymes
      constitute an independent component which can be added to any continuously
      operating system of purification without generating a specific interface which is
      crucially important in microgravity. This allows the process of purification to
      be controllable. The resulting water and air meet biological requirements because
      they are formed under the influence of living organisms as in natural
      biogeocenoses. The production of ecologically pure water and air is highly
      important for long-duration space missions, especially for flights to Mars.

PMID- 8577166
TI  - [Characteristics of prolactin secretion in response to different degrees of
      lesions of the vestibular analyzer].
AB  - The prolactin concentration in blood of 58 patients was measured during
      vestibular crisis and compensation of vestibular disorders. The results were
      compared with the clinical development of the disease and localization of
      vestibular problems. Patients with acute vestibular lesions at the central level
      of vestibular disorders showed a significant increase of prolactin concentrations
      that was higher than the concentrations in patients with the peripheral
      vestibular syndrome at the decompensation stage. Hyperprolactinemia during
      central vestibular dysfunction is viewed as a manifestation of dopamine
      deficiency of the tuberoinfundibular area. It is suggested that inadequacy of
      dopaminergic structures is one of the factors reducing adaptive and compensatory
      capabilities of the vestibular apparatus when its central compartments are
      injured.

PMID- 8577167
TI  - [Assessment of health status and metabolic parameters of cosmonauts during space
      flight].

PMID- 8577168
TI  - [Methods of complex assessment of the technological equipment of space flight
      medical facility].

PMID- 8577169
TI  - [Mathematical approach to the evaluation of accuracy of physiological
      measurements by different methods].

PMID- 8577170
TI  - [Basic approaches to the study of biological effects of heavy ions of galactic
      cosmic rays on space vehicles].

PMID- 8577171
TI  - [Analysis of blood proteins in rats after Cosmos-1887 flight by using two
      dimensional electrophoresis].

PMID- 8577172
TI  - [Study of biological activity of nidus vespae infusions during physical
      exercise].

PMID- 8577173
TI  - [Study of mental performance of MIR cosmonauts].
AB  - Prediction of mental performance is one of the major goals of space
      psychophysiology. This paper discusses experimental data about mental performance
      of the cosmonauts A. Alexandrov, A. Momanda, V. Savinykh and V. Polyakov as
      predicted by means of a Soviet-Bulgarian psychodiagnostic unit Pleven-87. The
      investigations were performed within the framework of the Prognosis experiment on
      Mir. The experimental results demonstrated that the psychodiagnostic unit Pleven
      87 provided reliable predictions, using adequate and sensitive methods. This unit
      can find application in mental performance evaluation and prediction.

PMID- 8577174
TI  - A rapid gas chromatographic method quantitating clozapine in human plasma or
      serum for the purpose of therapeutic monitoring.
AB  - A gas chromatographic method using nitrogen-phosphorus detection was developed to
      quantitate clozapine in plasma or serum. Methyl clonazepam was used as an
      internal standard. Sample preparation included a single-step extraction with
      ethyl acetate, which was injected directly onto a wide-bore capillary column.
      Within-run and total precision, measured as percent coefficient of variation,
      were determined at low, therapeutic, and high clozapine plasma concentrations.
      The within-run precision for the low, therapeutic, and high clozapine plasma
      samples was 5.2, 2.7, and 2.4%, respectively. The total precision for the low,
      therapeutic, and high clozapine plasma samples was 10.0, 2.6, and 2.0%,
      respectively. Analytical accuracy was evaluated by comparing quantitative results
      with those obtained from a reference laboratory. Those samples containing
      therapeutic or high concentrations agreed within 3%; the sample containing a
      subtherapeutic concentration differed by 11.9%. The limit of quantitation was
      determined to be 35 ng/mL, and the upper limit of linearity was 3000 ng/mL. No
      significant interferences were detected after testing more than two dozen drugs
      and metabolites.

PMID- 8577175
TI  - alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit
      methamphetamine synthesis: I. Physical characterization and GC-MS analysis of
      BNMPA and anticipated metabolites in urine.
AB  - alpha-Benzyl-N-methylphenethylamine (BNMPA) is an impurity of illicit
      methamphetamine synthesis. We synthesized BNMPA and three of its anticipated
      metabolites: N-demethyl-alpha-benzyl-phenethylamine, 1,3-diphenyl-2-propanone,
      and 1,3-diphenyl-2-propanol. The purity and structure of these compounds and
      their heptafluorobutyric anhydride (HFBA) derivatives were confirmed by melting
      point, gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic
      resonance. A GC-MS method to detect these compounds in urine, using liquid-liquid
      extraction and derivatization with HFBA, was developed. Interference studies
      showed BNMPA and its proposed metabolites to be well-resolved from other common
      phenethylamine drugs and Health and Human Services-Forensic Urine Drug Testing
      required analytes. The limit of detection of BNMPA and its metabolites was 2.5
      ng/mL; the limit of quantitation (LOQ) of the four compounds was 25 ng/mL. The
      calibration curves were generally linear from 25 to 500 ng/mL. Typical within-run
      coefficients of variation (CVs) at the LOQ ranged from 13 to 20% (n = 8). Between
      run CVs over 1 month at 25 ng/mL were from 9 to 28%, and at 500 ng/mL, they were
      from 2.6 to 3.9%. The detection of BNMPA or its metabolites in urine samples may
      provide a marker of use of illicitly synthesized methamphetamine.

PMID- 8577176
TI  - alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit
      methamphetamine synthesis: II. Metabolism and urinary excretion (human).
AB  - Methamphetamine is a popular drug of abuse, which is readily synthesized in
      clandestine laboratories. Illicit synthesis results in the formation of various
      contaminants. Few impurities have been studied in vivo, and their metabolic fate
      is unknown. One such impurity is alpha-benzyl-N-methylphenethylamine (BNMPA). The
      detection of BNMPA or its metabolites in urine samples may provide a marker of
      use of illicitly synthesized methamphetamine. Benzphetamine is structurally
      similar to BNMPA. Based on metabolic studies of benzphetamine, we predicted the
      four major metabolites of BNMPA to be the N-demethyl compound, diphenyl-2
      propanone (DP2P), p-hydroxy-N-demethyl BNMPA, and p-hydroxy-BNMPA. One male
      volunteer ingested 5 mg BNMPA. Seventeen urine specimens were collected over 50 h
      post ingestion. These specimens were analyzed for BNMPA and its four predicted
      major metabolites by gas chromatography-mass spectrometry following beta
      glucuronidase hydrolysis or acid hydrolysis, liquid-liquid extraction, and
      derivatization with heptafluorobutyric anhydride. Specimens were also analyzed
      without hydrolysis to determine the abundance of nonconjugated ("free")
      metabolites. Only trace amounts of BNMPA and its N-demethyl metabolites were
      detected, and maximum excretion was from 2 to 4 h post ingestion. In the
      nonhydrolyzed samples, the phenyl-OH metabolites were also present in only trace
      amounts. Maximum excretion of DP2P was at 2 h. Following either hydrolysis
      procedure, phenyl-OH-BNMPA and phenyl-OH-N-demethyl BNMPA were the major
      metabolites detected. Maximum excretion of these two metabolites occurred at 4 h.
      With the exception of the parent compound and the N-demethyl metabolite,
      excretion of metabolites was greater than the limit of detection of this
      procedure (2.5 ng/mL) up to 21 h post ingestion. Metabolites were detectable in
      sufficient quantities to serve as an adequate marker of illicit methamphetamine
      consumption within the preceding 24 h.

PMID- 8577177
TI  - False-positive postmortem EMIT drugs-of-abuse assay due to lactate dehydrogenase
      and lactate in urine.
AB  - Three cases of multiple false-positive drug tests are described. Postmortem urine
      specimens were screened using the enzyme-multiplied immunoassay technique. All
      patients had proteinuria and lactic aciduria. These false-positive reactions were
      due to the presence of lactate dehydrogenase (LDH), lactic acid, and protein.
      This finding was confirmed by creating a multiple false-positive sample with a
      solution of LDH and lactate in 5% bovine serum albumin at pH 6.

PMID- 8577178
TI  - A method for the simultaneous identification and quantitation of five
      superwarfarin rodenticides in human serum.
AB  - A high-performance liquid chromatographic method with ultraviolet (UV) and
      fluorescence detection was developed for the analysis of one indandione and four
      hydroxycoumarin anticoagulant rodenticides in human serum. The superwarfarin
      rodenticides, chlorophacinone, bromadiolone, difenacoum, brodifacoum, and
      difethialone, can be identified and quantitated simultaneously with this method.
      After adding a buffer (pH 5.5), the anticoagulants were extracted from serum with
      chloroform-acetone. The organic phase was separated and evaporated to dryness,
      and the residue was subjected to chromatographic analysis. The anticoagulants
      were separated by reversed-phase chromatography and detected by UV absorption at
      285 nm and by fluorescence at an excitation wavelength of 265 nm and an emission
      wavelength of 400 nm. Extraction efficiencies from 55 to 131% were obtained. The
      within-run precision ranged from 2.0 to 7.1% for UV detection and from 0.0 to
      4.8% for fluorescence detection. Between-run precision ranged from 1.3 to 16.0%
      for UV detection and from 1.8 to 9.0% for fluorescence detection. The
      anticoagulants can be quantitated at serum concentrations down to 3-12 ng/mL for
      fluorescence detection and down to 20-75 ng/mL for UV detection. No interferences
      were observed with the related compounds warfarin and vitamin K1.

PMID- 8577179
TI  - Metabolism of 4-methylaminorex ("EU4EA") in the rat.
AB  - Metabolism studies were conducted on 4-methylaminorex (4,5-dihydro-4-methyl-5
      phenyl-2-oxazolamine [4-MAX]), a potent central nervous system stimulant that has
      emerged as a drug of abuse under the name "EU4EA", "EU4Euh", and "Ice". Tritiated
      norephedrine was cyclized with cyanogen bromide to form 3H-4-MAX, which was
      administered to rats at a dose of 10 mg/kg orally and intravenously.
      Radioactivity was excreted almost entirely in urine (40% of the dose was excreted
      by 24 h), primarily as the parent drug (60% of the total excretions were as the
      parent compound). Three metabolites were identified by high-performance liquid
      chromatography-tandem mass spectrometry with thermospray ionization:
      norephedrine, 5-phenyl-4-methyl-2-oxazolidinone, and 2-amino-5-(p-hydroxyphenyl)
      4-methyl-2-oxazoline. Stability studies showed that 4-MAX in aqueous solution
      degraded very slightly to norephedrine upon standing. There was no evidence for
      glucuronide or sulfate conjugation. These results suggest that the metabolic fate
      of 4-MAX is similar to that of the amphetamines in that it is eliminated
      primarily unchanged but undergoes some slight oxidative deamination and aromatic
      hydroxylation. Hydrolytic degradation back to the synthetic precursor can also
      occur. There was no evidence for the hydrolysis of the oxazolamine ring to form a
      urea that has been reported for the demethylated congener aminorex. This suggests
      that 4-methyl substitution of the oxazoline ring may inhibit metabolism similar
      to the alpha-methyl substitution of beta-phenylethylamines.

PMID- 8577180
TI  - Cocaine, ecgonine methyl ester, and benzoylecgonine plasma profiles in rhesus
      monkeys.
AB  - From a public health point of view, cocaine (COC) presents serious clinical
      problems and deaths from overdose and lifelong addiction patterns, not to mention
      its involvement in crime, in the United States. This study subjected rhesus
      monkeys to one intravenous administration of COC (1 mg/kg), which closely
      imitates the smoking of "crack" COC with regard to dose and effect. We monitored
      plasma concentrations over time, beginning when the primates were in a state of
      hyperarousal. Blood was sampled at 1, 6, 12, and 40 min after dosing. Plasma
      concentrations of COC decreased rapidly with a half life of 15.7 min. Mean COC
      concentrations in the drug-treated group (n = 7) for the four timepoints were
      296, 225, 187, and 80 ng/mL, respectively. Ecgonine methyl ester (EME)
      concentrations ranged from 57 to 91 ng/mL. When compared with the 1-min COC
      concentrations, the mean EME concentration was 30.7%. Benzoylecgonine (BZE)
      ranged from 34 to 42 ng/mL, and the mean concentration was 11.5% of the mean COC
      concentration at 1 min. EME and BZE concentrations did not vary appreciably over
      the time course of the study. Plasma norcocaine concentrations were less than the
      limit of detection of 25 ng/mL. Because a rapid decline in plasma COC
      concentrations over time was observed along with a very small change in EME and
      BZE concentrations, we attribute tissue redistribution of COC, particularly to
      the brain, as significant and metabolism or hydrolysis of COC as minor.

PMID- 8577181
TI  - Anticoagulant poisoning in animals: a simple new high-performance thin-layer
      chromatographic (HPTLC) method for the simultaneous determination of eight
      anticoagulant rodenticides in liver samples.
AB  - The purpose of this study was to develop and evaluate a technique for the
      analysis of anticoagulant rodenticides in serum and liver samples using a new
      high-performance thin-layer chromatographic apparatus. Detection limits were
      estimated at 0.2 micrograms/g in liver extracts for eight different substances.
      Overall, this technique was repeatable and reproducible. The percent recovery was
      greater than 87% for each substance. Liver and serum samples of animals known to
      be exposed to one anticoagulant and showing clinical signs of poisoning were
      analyzed. Concentrations measured varied between 0.2 and 3 micrograms/g (liver
      extracts). Only blood samples from one dog could be analyzed. The concentration
      was 150 ng/mL the first day after admission and 140 ng/mL the following day.
      Analyses are technically easily and rapidly performed, and they are inexpensive.
      Therefore, this technique could be a valuable alternative to current high
      performance liquid chromatographic methods.

PMID- 8577182
TI  - GC-MS determination of amphetamine and methamphetamine in human urine for 12
      hours following oral administration of dextro-methamphetamine: lack of evidence
      supporting the established forensic guidelines for methamphetamine confirmation.
AB  - Ten human volunteers, naive to amphetamines and divided into two groups of five
      each, were given an oral dose of 30 mg/70 kg D-methamphetamine in one of two
      different paradigms: the initial dose at 0930 h or the initial dose at 2130 h.
      One week later, each subject was crossed over with regard to time but given the
      same dose. A total of 214 urine specimens were collected either prior to dosing
      or at each micturition for a 12-h period post dose. Specimens were analyzed on a
      blind basis for methamphetamine and one of its metabolites, amphetamine, by gas
      chromatography-mass spectrometry (GC-MS) using coinjection of extracted sample
      and pentafluoropropionic anhydride and selected-ion monitoring. Approximately 20%
      of the D-methamphetamine was recovered unchanged from the urine specimens, and 2%
      was recovered as amphetamine. The mean urine methamphetamine concentration in
      both groups reached a maximum within 4-6 h and declined thereafter. A residual
      amount of methamphetamine was found in some predose specimens at the crossover
      evaluation, reflecting that methamphetamine may be detected in urine for up to 7
      days. The amphetamine concentration reached a plateau by 4-6 h. This observation
      coupled with the finding that all subjects excreted approximately 2% of the
      methamphetamine dose as amphetamine suggested a saturable process for its
      biotransformation. Concentrations of both methamphetamine and amphetamine tended
      to be higher, but were not significantly different, for night administration.
      Methamphetamine concentrations were consistently greater than the 500-ng/mL
      cutoff in most post-dosing specimens, whereas amphetamine concentrations
      generally did not achieve the 200-ng/mL cutoff specified by the Substance Abuse
      and Mental Health Services Administration (SAMHSA) guidelines for GC-MS
      confirmation of methamphetamine. Some specimens containing methamphetamine had no
      amphetamine metabolite. The current guidelines would have resulted in 90.2% of
      the specimens containing methamphetamine being ruled negative by confirmation
      following either night or day administration, whereas one subject following the
      initial day administration and another following night crossover administration
      would have been judged positive at most time intervals. These findings suggest
      that the current SAMHSA guidelines select for individual metabolic variations and
      that GC-MS confirmation of methamphetamine will result in most occasional users
      being ruled negative following an oral dose of methamphetamine while some will be
      ruled positive.

PMID- 8577183
TI  - A fatal case of alimemazine poisoning.
AB  - Alimemazine, a phenothiazine derivative with the properties of antihistamines,
      was determined by a selective high-performance liquid chromatographic technique
      in blood and tissues from a postmortem case. The blood concentration of
      alimemazine was 6.52 micrograms/mL. The brain was the major site of drug
      deposition, and tissue distribution is discussed in light of the existing
      literature.

PMID- 8577184
TI  - David Hubel--Nobel Prize winner for investigations of brain function.

PMID- 8577185
TI  - Prognosis of patients with acute renal failure in the intensive-care unit: a tale
      of two eras.
AB  - OBJECTIVE: To determine whether any changes occurred in the complexity of illness
      or survival of Mayo intensive-care unit (ICU) patients with acute renal failure
      (ARF) who required hemodialysis between the 1977 through 1979 period and the 1991
      and 1992 era. DESIGN: A retrospective comparison was done of 71 consecutive ICU
      patients with ARF during 1977 through 1979 and 71 similar consecutive patients
      from the 1991 and 1992 period. MATERIAL AND METHODS: Each patient was scored for
      the three components of the acute physiology and chronic health evaluation
      (APACHE) II system (acute physiology score, age, and preexisting chronic health
      problems). Patient gender, postoperative status, presence of diabetes mellitus,
      presence of chronic renal insufficiency, and factors contributing to ARF were
      recorded for each patient. Patient survival and renal function at time of
      hospital dismissal and 12 months after initiation of hemodialysis were
      determined. RESULTS: In comparison with patients in the earlier study period,
      those in the later study period had a signficantly improved rate of hospital
      survival (52% versus 32%) and 1-year survival (30% versus 21%). At 1 year, 96%
      and 78% of survivors in the earlier and later study groups, respectively, had
      recovery of renal function. The mean total APACHE II score was the same in both
      study periods, but patients in the later group were older and had more APACHE II
      points for chronic health problems. In the earlier and later study groups,
      patients with an APACHE II score of 21 or lower had a mortality rate of 36% and
      11%, respectively, and survival among those with a score of 34 or greater was 0%
      and 15%, respectively. In 1991 and 1992, more patients had two or more factors
      contributing to the development of ARF, and intravenous administration of a
      contrast agent and preexisting cardiac prerenal compromise were more frequent
      causes of ARF than in 1977 through 1979. The occurrence of sepsis and preexisting
      lung disease were associated with a dismal prognosis in both study periods. In
      1991 and 1992, survival was improved for patients with preexisting diabetes
      mellitus, postoperative status, and contrast-induced renal failure. CONCLUSION:
      The prognosis of ICU patients with ARF has improved in more recent years, despite
      the fact that patients are now older, have more preexisting chronic health
      conditions, and have an increasing number of conditions contributing to
      development of ARF. The APACHE II scoring system demonstrated utility for
      quantifying the complexity of illness in these patients, but several important
      shortcomings may limit its usefulness as a comparative or prognostic tool in
      patients with ARF.

PMID- 8577186
TI  - Effect of feedback on resource use and morbidity in hip and knee arthroplasty in
      an integrated group practice setting.
AB  - OBJECTIVE: To assess the effect of a structured program of feedback about
      resource utilization and morbidity on resource consumption and complications in
      an orthopedic surgical practice. DESIGN: We prospectively analyzed use and
      outcomes before and after an intervention (departmental data presentation).
      MATERIAL AND METHODS: Feedback on resource utilization and morbidity for 2,820
      patients who underwent a primary total hip or knee arthroplasty for a diagnosis
      of osteoarthritis between Jan. 1, 1990, and Dec. 31, 1992, was provided to
      members of the orthopedic department of an academic medical center. Data were
      adjusted for severity of disease. RESULTS: On reassessment 18 months after the
      beginning of the feedback program, total charges and length of hospital stay for
      hip or knee arthroplasty were significantly reduced. Interpractitioner
      variability was also reduced but not significantly. The feedback process was
      instrumental in identifying a specific complication--pulmonary embolism after
      bilateral total knee replacement--which was significantly reduced by addition of
      warfarin prophylaxis. CONCLUSION: The intervention was successful in reducing
      resource use (length of hospital stay) and complications (pulmonary embolism). In
      addition, total charges for hip and knee arthroplasty declined significantly at a
      time when medical center charges overall were increasing. Efforts to maintain
      continuous improvement will primarily focus on the development of critical
      pathways.

PMID- 8577187
TI  - Usefulness of intracardiac echocardiography in complex transseptal
      catheterization during percutaneous transvenous mitral commissurotomy.
AB  - OBJECTIVE: To examine the utility of intracardiac echocardiography in guiding
      complex transseptal catheterization of patients undergoing percutaneous
      transvenous mitral commissurotomy. DESIGN: We assessed this procedure in high
      risk patients in whom transseptal catheterization is technically complex and more
      demanding. MATERIAL AND METHODS: Fifteen patients with mitral stenosis were
      studied. Twelve patients had giant left atria (70 mm or more), two had atrial
      septal aneurysms, and one had severe kyphoscoliosis. A newly developed 8-F 10-MHz
      intracardiac transducer catheter was placed in the right atrium through an 8-F
      Mullins sheath inserted from the left femoral vein. Echocardiographic images were
      used to confirm the septal position of the Brockenbrough needle tip before septal
      punctures. RESULTS: Transseptal puncture was successful and uncomplicated in all
      15 patients. Use of intracardiac echocardiography eliminated the need for atrial
      angiography. Before transseptal puncture, the needle tip was identified to be in
      contact with the atrial septum, as an echogenic point with its acoustic shadow
      and septal indentation. In addition, in the two patients with aneurysms, puncture
      of the thin-walled aneurysms was avoided. CONCLUSION: Intracardiac
      echocardiography facilitates safe complex transseptal catheterization in patients
      with mitral stenosis and giant left atria, atrial septal aneurysms, or severe
      kyphoscoliosis.

PMID- 8577188
TI  - Effect of Doppler echocardiography on utilization of hemodynamic cardiac
      catheterization in the preoperative evaluation of aortic stenosis.
AB  - OBJECTIVE: To examine the use of Doppler echocardiography in preoperative
      assessment of aortic stenosis and to determine its effect on subsequent use of
      hemodynamic cardiac catheterization. MATERIAL AND METHODS: We retrospectively
      reviewed a consecutive series of 574 adult patients who underwent aortic valve
      replacement for aortic stenosis between 1990 and 1992 at our institution. The use
      of Doppler echocardiography and cardiac catheterization and the predictive
      factors for use of hemodynamic catheterization were analyzed. RESULTS: After
      Doppler echocardiography in 423 patients, invasive hemodynamic assessment of the
      severity of aortic stenosis was performed in only 42% (179 patients). The use of
      cardiac catheterization declined over time (54% in 1990, 40% in 1991, and 35% in
      1992) (P = 0.003), whereas no significant change in the baseline clinical
      characteristics of the population or in severity of stenosis as determined by
      Doppler echocardiography occurred during that time. Multivariate analysis
      identified the following variables as independent predictors of use of cardiac
      catheterization after Doppler echocardiography: clinically not severe aortic
      stenosis, mean gradient of less than 50 mm Hg determined by Doppler
      echocardiography, Doppler-determined aortic valve area of more than 0.8 cm2 or
      not calculated, attending cardiologist not specialized in echocardiography, and
      earlier year of assessment. CONCLUSION: After Doppler echocardiography, less than
      50% of our patients undergoing aortic valve replacement for aortic stenosis have
      cardiac catheterization preoperatively. The use of cardiac catheterization after
      Doppler echocardiography--thus, duplication of hemodynamic assessment--declined
      significantly over time during the study period. Decline in the use of
      catheterization is related to the degree of diagnostic certainty provided by
      Doppler echocardiography and to the level of familiarity of the attending
      cardiologist with the technique.

PMID- 8577189
TI  - Management of atrial fibrillation in adults: prevention of thromboembolism and
      symptomatic treatment.
AB  - Because of its prevalence in the population and its associated underlying
      diseases and morbidity, atrial fibrillation (AF) is an important and costly
      health problem. Advancing age, diabetes, heart failure, valvular disease,
      hypertension, and myocardial infarction predict the occurrence of AF within a
      population. The management of AF is complex and involves prevention of
      thromboembolic complications and treatment of arrhythmia-related symptoms. Stroke
      occurs in 4.5% of untreated patients with AF per year. Independent risk factors
      for stroke in nonrheumatic patients with AF are advanced age; a history of prior
      embolism, hypertension, or diabetes; and echocardiographic findings of left
      atrial enlargement and left ventricular dysfunction. Warfarin decreases stroke by
      two-thirds and death by one-third; aspirin is only about half as effective
      overall and is insufficient therapy for those with risk factors for stroke.
      Options for thromboembolic prophylaxis are use of warfarin for all in whom it is
      safe or, alternatively, warfarin for those with risk factors and aspirin for
      those without risk factors. One-half of the patients with AF are 75 years of age
      or older. The uniform applicability and relative safety of warfarin therapy in
      this age-group are controversial. Specific therapy for the arrhythmia should be
      dictated by the need to control symptoms. Symptomatic treatments include rate
      control medications and strategies designed to terminate and prevent arrhythmia
      recurrence. Digoxin, beta-adrenergic blockers, verapamil, and diltiazem slow
      excessive ventricular rates in patients with AF and may favorably manage comorbid
      conditions. The efficacy of anti-arrhythmic medications is only 40 to 70% per
      year in preventing recurrences of AF, and these agents, except amiodarone, may
      increase the risk of sudden death in patients with certain types of organic heart
      disease and AF. The use of nonpharmacologic symptomatic therapies such as
      atrioventricular node modification or ablation with a rate-response pacemaker or
      surgical intervention is increasing.

PMID- 8577190
TI  - Successful treatment of intrathecal methotrexate overdose by using
      ventriculolumbar perfusion and intrathecal instillation of carboxypeptidase G2.
AB  - Prompt and appropriate management measures are critical in order to achieve a
      favorable outcome after a major overdose of intrathecally (IT) administered
      methotrexate (MTX). Published information available to guide clinicians in the
      immediate management of this medical emergency is scant. Herein we describe a 6
      year-old boy with acute lymphoblastic leukemia who received an inadvertent
      overdose of 600 mg of IT administered MTX instead of the intended dose of 12 mg.
      Severe acute neurotoxicity developed rapidly. Lumbar puncture and drainage of 15
      mL of cerebrospinal fluid 2 hours after administration resulted in removal of 32%
      of the administered drug. Ventriculolumbar perfusion with 240 mL of warmed
      isotonic saline through ventricular and lumbar catheters for 3 hours resulted in
      removal of a total of 90% of the drug within 8 1/2 hours after administration. IT
      administration of 2,000 U of carboxypeptidase G2 (CPDG2), an enzyme that
      inactivates MTX, resulted in a further 150-fold reduction in cerebrospinal fluid
      MTX concentration. The patient experienced complete recovery. To our knowledge,
      this is the first reported case of the use of IT instillation of CPDG2 for the
      treatment of an overdose of IT administered MTX in a human, and it is only the
      second reported favorable outcome after an IT overdose of more than 500 mg of
      MTX. Minor IT overdoses of MTX can be managed by immediate lumbar drainage alone.
      Major overdoses may also necessitate prompt ventriculolumbar perfusion, IT
      instillation of CPDG2, and further supportive measures for a successful outcome
      after this infrequent but potentially catastrophic event.

PMID- 8577191
TI  - Aleukemic monocytic leukemia cutis.
AB  - Aleukemic leukemia cutis is a rare condition in which leukemic cells invade the
      skin before they appear in peripheral blood or bone marrow specimens. Herein we
      describe a 67-year-old man who underwent assessment because of papules and
      nodules on his back and lower extremities. A biopsy of these lesions confirmed a
      dense, predominantly monocytic infiltrate of the dermis and subcutaneous tissue.
      Immunohistochemical stains were positive for CD43 (Leu-22) as well as monocytic
      markers. Bone marrow and peripheral blood examinations failed to reveal leukemia.
      Treatment was based on the results of the skin biopsy, and the patient is doing
      well 1 year after therapy.

PMID- 8577192
TI  - Lumbar and caudal epidural corticosteroid injections.
AB  - OBJECTIVE: To describe the indications, rationale, techniques, alternatives,
      contraindications, complications, and efficacy of lumbar and caudal epidural
      corticosteroid injections. DESIGN: Case reports and retrospective and prospective
      studies were extensively reviewed to provide detailed descriptions of the
      clinical features of lumbar and caudal epidural corticosteroid injections.
      RESULTS: Epidural corticosteroid injections are commonly requested treatments for
      patients with various low-back or lower-extremity pain syndromes (or both). Most
      of the reports on the use of this type of treatment are retrospective and
      noncontrolled. These studies indicate benefit; however, the prospective
      controlled studies provide varied results about the efficacy of lumbar and caudal
      epidural corticosteroid injections. CONCLUSION: A thorough analysis of the few
      available controlled studies and their limitations indicates that this treatment
      is probably efficacious for patients with certain lower-extremity radicular pain
      syndromes when intermediate-term (2 weeks to 3 months) results are assessed after
      injection. More studies are needed to elucidate further the most beneficial
      candidates and techniques.

PMID- 8577193
TI  - Concise review for primary-care physicians.
AB  - Acute otitis media (AOM) in young children consumes a substantial amount of
      medical care services provided by primary-care physicians. A recent increase in
      the number of young children with AOM prompted a review of the associated risk
      factors. Eustachian tube dysfunction, bacterial colonization, and host
      inflammatory response form the basis for the development of AOM. Signs and
      symptoms of AOM in young children are often nonspecific and subtle, particularly
      in infants. Physical examination and pneumatic otoscopy verify the diagnosis. New
      modalities including tympanometry and acoustic reflectometry may be helpful.
      Amoxicillin remains the drug of choice for AOM, despite recent trends in
      microbial resistance. Second- and third-line antimicrobial agents might be
      considered in selected clinical settings. Young children with recurrent episodes
      of otitis media must be monitored closely. Preventive measures and medical or
      surgical intervention should be considered in order to minimize the long-term
      medical and developmental effects of AOM.

PMID- 8577194
TI  - Cardiovascular disease in elderly patients.
AB  - OBJECTIVE: To provide an overview of the cardiovascular consequences of the
      normal aging process in humans and to review unique aspects of the diagnosis and
      management of heart disease in the elderly population. DESIGN: We reviewed
      relevant published articles and summarized the diagnostic approaches and
      treatment recommendations for congestive heart failure, coronary artery disease,
      cardiac valvular disease, and arrhythmias in elderly patients. RESULTS: The aging
      process is associated with predictable anatomic and physiologic alterations in
      the cardiovascular system. consequently, the manifestations of heart disease in
      the geriatric population differ from those found in younger patients.
      Additionally, outcomes of cardiac diseases and therapeutic options change with
      advancing age because of such factors as alterations in drug metabolism.
      CONCLUSION: Age-related changes in the cardiovascular system result from
      intrinsic cardiac aspects of human senescence, primary cardiac disease, and
      influence of comorbid conditions on the heart. The natural history of heart
      disease is generally adversely affected by age. Although many treatment
      strategies with demonstrated efficacy in younger patients are relevant in the
      elderly age-group, careful attention to the influence of concomitant illness, the
      unique physiologic and pharmacologic changes, and the assessment of the potential
      effect of therapy on survival and quality of life is essential in treating
      elderly patients.

PMID- 8577195
TI  - 68-year-old man with anemia and renal failure.

PMID- 8577196
TI  - Teaching residents about managed care.

PMID- 8577197
TI  - Renal failure in the intensive-care unit: an old tale gets better.

PMID- 8577198
TI  - Hips and knees: state of evidence regarding effectiveness of quality improvement
      interventions in orthopedic surgery.

PMID- 8577199
TI  - Estrogen replacement therapy.

PMID- 8577200
TI  - Estrogen replacement therapy.

PMID- 8577201
TI  - Radiotherapy for oral manifestations of Kaposi's sarcoma.

PMID- 8577202
TI  - Radiotherapy for oral manifestations of Kaposi's sarcoma.

PMID- 8577203
TI  - Central effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) in mice.
AB  - The central effects of endothelin-1 (ET-1, 0.5, 1, 2.5 and 10 pmol/mouse) and
      endothelin-3 (ET-3, 2.5, 5, 10, 20 and 25 pmol/mouse) have been studied after
      intracerebroventricular (i.c.v.) administration in mice. The following methods
      were used: behavioral observations, rotarod, spontaneous and amphetamine
      stimulated motor activity, and hexobarbital-induced narcosis. ET-1 and ET-3
      evoked a dose-dependent behavioral syndrome with a short excitatory period in the
      higher doses lasting for 5-10 min, followed by a prolonged depressive phase
      (about 90 min). ET-1 and ET-3 produced central depressive effects demonstrated by
      depressive behavior signs, decrease of the spontaneous and amphetamine-stimulated
      motor activity, and prolongation of the hexobarbital-induced narcosis.

PMID- 8577204
TI  - Different effects of three high-dose oral calcium salts on acid-base metabolism,
      plasma electrolytes and urine parameters of rats.
AB  - The oral calcium (Ca) load test has been applied to estimate the enteral
      absorbability of Ca salts in humans; provided that the deep bone compartments are
      filled up, excess Ca should be excreted in the urine. Using this "overflow model"
      three Ca salts were tested in rats at increasing oral doses of 0 to 14 mmol/kg
      body weight: CaCO3 and two other compounds containing chloride at a Ca:Cl ratio
      of 1:2 (CaCl2) and 1:1 (Ca-aspartate-hydrochloride). The carbonate was poorly
      absorbed and hence did not significantly affect acid-base metabolism nor urine
      pH. Both chloride-containing salts increased Ca excretion to a significantly
      higher degree in a dose-dependent manner; in contrast to the organic compound,
      the CaCl2 induced metabolic acidosis at 14 mmol/kg body weight. At decreasing
      base excess and urinary pH, renal excretion of Ca and of magnesium (Mg)
      increased, indicating that acid-base alterations must be considered when
      evaluating the oral load test. All Ca salts induced moderate hypomagnesemia
      pointing to decreased enteral absorbability of food-borne Mg in rats. Studies on
      volunteers reported in the literature suggest, however, that this effect is not
      relevant for humans.

PMID- 8577205
TI  - Effects of iloprost on salt-sensitive Dahl rats.
AB  - The main pharmacological effects of iloprost, a stable prostacyclin (PGI2)
      derivative, are inhibition of platelet aggregation and vasodilatation, both
      effects being mediated by an activation of adenylate cyclase/cAMP complex. Na+
      has an opposite, inhibiting adenylate cyclase effect on plasma membrane. The
      effect of iloprost (1 microgram/kg/min) was investigated on mean arterial
      pressure, bleeding time, in vivo platelet aggregation to collagen and plasma
      thromboxane A2/PGI2 in genetically salt-sensitive Dahl rats (12) and their salt
      resistant controls (12). In this subhypotensive dose, iloprost significantly
      increased bleeding time and plasma PGI2 levels in both groups and significantly
      decreased TXA2 levels. In vivo platelet aggregation to collagen was significantly
      inhibited in both groups. All described effects were more distinct in salt
      sensitive, compared to salt-resistant rats (differences were significant). A
      modulation of Na+ effect by iloprost, via adenylate cyclase mechanism, was
      suggested.

PMID- 8577206
TI  - Morphine-induced alterations on DNA-binding proteins in developing rat brain.
AB  - Endogenous opioids and opiate drugs inhibit nervous system maturation through
      both direct and indirect mechanisms. Recently much attention has been directed
      toward changes in the postreceptor events and it has been speculated that the
      regulation of gene expression may be involved in the development of drug
      tolerance and dependence. We investigated the changes in the levels of in vitro
      RNA synthesis in developing rat brain after continuous block of opioid receptors.
      Repeated naloxone treatment induced increased levels (27-48%) of RNA synthesis
      during the early postnatal period. Using mobility gel shift assay the presence of
      octamer binding proteins (Oct-1) and the replication differentiation
      transcription factor CTF/NF1 in the developing rat brain were studied both after
      single or repeated morphine and naloxone treatment. Decreased Oct-1 binding
      activity in brain protein extracts 1 h after morphine application was registered,
      while opioid antagonist naloxone exerted an opposite effect on this octamer
      protein following single drug treatment. Repeated administration of morphine or
      naloxone decreased markedly the DNA-binding affinity of Oct-1. The binding
      activity of CTF/NF1 changes differently showed higher levels assessed 30-120 min
      after morphine administration. The opposite trend of the changes in opiate drug
      and opioid antagonist animals suggests opioid receptor-mediated regulation of Oct
      1 and CTF/NF1 transcription factors.

PMID- 8577207
TI  - Comparison of the characteristics and density of dopamine-1 receptors in
      membranes from different arteries using [3H]SCH23390 binding.
AB  - By using radioreceptor binding techniques and [3H]SCH23390 as a ligand, a
      comparative study was performed on the pharmacological properties and the density
      of dopamine-1 (D1) receptors in different vascular systems. [3H]SCH23390 was
      specifically bound to membranes from rabbit renal, mesenteric and pulmonary, but
      not femoral, arteries. The binding was saturable and in a manner consistent with
      the labeling of D1 receptors. The Kd value and Hill coefficient (nH) were similar
      in all three arteries with no statistically significant differences (p > 0.05)
      among them, indicating a homogenous binding site with a single class of high
      affinity. In competitive binding tests, the selective D1 antagonist and agonist
      inhibited the binding much more potently than the D2 antagonist, indicating a
      pharmacological characteristic of D1 receptors. The Bmax values, however,
      differed considerably among these arteries, with the value being the largest in
      the renal artery and smallest in the pulmonary artery. These findings are
      indicative of the existence of D1 receptor sites with identical properties but
      diverse density in different vascular beds, which underlies the relative
      functional importance of the receptors in regulating local blood flow in distinct
      vessels.

PMID- 8577208
TI  - Effects of the beta-adrenergic blockers propranolol and acebutolol on stress
      induced learned helplessness behavior of rats.
AB  - The latency time and escape ability of rats with learned helplessness behavior
      were studied after 1, 6 and 14 days of oral treatment with beta-adrenergic
      blockers propranolol (1 and 3 mg/kg) and acebutolol (10 and 30 mg/kg). A dose
      dependent significant decrease in latency time and increase in number of
      avoidances was established after single, 6 and 14 days propranolol treatment. The
      selective beta 1-blocker acebutolol did not change the escape characteristics.
      These results suggest a greater impact of beta 1- than beta 2-adrenergic
      receptors for escape performance after unescapable foot shock, i.e., learned
      helplessness behavior.

PMID- 8577209
TI  - Staurosporine inhibits the effects of leukotrienes C4 and D4 in isolated guinea
      pig heart and trachea.
AB  - Isolated hearts from guinea pigs were perfused at 37 degrees C with Tyrode's
      solution according to the technique of Langendorff. Coronary flow, left
      ventricular pressure amplitude and heart rate were measured. Bolus injection of
      30 ng leukotriene C4 caused a long-lasting decrease in coronary flow and left
      ventricular pressure amplitude while heart rate was not affected. A similar but
      shorter lasting effect was induced by 100 ng leukotriene D4. The effects of the
      leukotrienes were completely blocked by 1 microM staurosporine. Staurosporine at
      concentrations of 100 and 10 nM, in contrast to 1 microM, influenced basic
      cardiac function slightly or not at all, but antagonized the effects of 30 ng
      leukotriene C4. In isolated tracheal muscle preparations, leukotriene C4 and D4
      induced concentration-dependent contractures. Staurosporine at concentrations of
      25-100 nM antagonized the effects of leukotriene C4 and D4 in a noncompetitive
      manner with inhibitor constants of 47.6 and 75.9 nM, respectively. The results
      indicate that staurosporine is a potent noncompetitive antagonist of the effects
      of leukotriene C4 and D4 in smooth muscle.

PMID- 8577210
TI  - Meperidine uptake and binding to human blood ex vivo.
AB  - Many drugs are bound to plasma proteins (PR) and/or to erythrocytes (RBC). The
      RBC count may change due to physiologic factors such as exposure to high
      altitude, or pathologic conditions such as anemia or as consequence of cancer
      treatment. The purpose of the investigation was to study the influence of 1) drug
      concentration, and 2) number of RBC on erythrocyte uptake or binding using
      meperidine as a model drug (M). Human RBC concentrated blood was used and blood
      chemistry determined. Using human plasma (P) dilutions were made containing 9.9,
      7.62, 5.87 and 4.11 million RBC mm3. The whole blood (WB) samples were spiked
      with M to result in 10, 25, 50, or 75 micrograms/ml. Increasing concentrations of
      M within each group of same RBC count did not influence percentage of erythrocyte
      uptake/binding. Increase in RBC count from 4.11 to 9.9 million/mm3 resulted in
      significant increase in erythrocyte uptake from 77.1% to 94.7% and increase in PR
      binding from 37.2% to 87.4%.

PMID- 8577211
TI  - Influence of food on the disposition of the antidiabetic drug metformin in
      diabetic patients at steady-state.
AB  - The effect of food on the bioavailability of the antidiabetic drug metformin
      (Glucophage, Lipha Laboratories) was investigated in patients at steady-state.
      Seventeen diabetic patients (5 males and 12 females) treated with a long-term
      metformin therapy received their morning dose after an overnight fasting or after
      each of four types of breakfast: low protein, low fat, low carbohydrate or
      standard. Mean (+/- SD) and median areas under the serum concentration curves
      (AUC), maximum concentrations (Cmax) and time to reach the Cmax (Tmax) were
      calculated. Compared to fasting conditions, AUC and Cmax for metformin were
      bioequivalent after the four types of breakfast except the low fat (high
      carbohydrate) diet which had results slightly reduced (90% CI = [0.76-0.90]). The
      intraindividual variability was calculated and found to be lower than the
      interindividual variability.

PMID- 8577212
TI  - Effect of four lansoprazole dose levels and one dosage regimen of omeprazole on
      24-hour intragastric pH in healthy subjects.
AB  - Lansoprazole is a potent proton pump inhibitor and blocks gastric acid secretion.
      The potency of many antibiotics in eradicating Helicobacter pylori may be
      considerably enhanced by increasing the intragastric pH due to a twice-daily
      coadministration of proton pump inhibitors. This double-blind crossover study was
      designed to compare the effect on intragastric pH of four dose regimens of
      lansoprazole (30 mg o.a.d., 30 mg b.i.d., 45 mg b.i.d., 60 mg b.i.d.) after 5
      days of treatment and to investigate whether an increment of lansoprazole dose
      level leads to a more pronounced effect. Omeprazole 20 mg b.i.d. was administered
      as a reference drug. The study was carried out in 20 healthy male subjects.
      Intragastric pH was recorded by a nasogastric probe over 24 h. All dose regimens
      of lansoprazole were well tolerated and no unexpected drug-related adverse events
      were observed. The lowest lansoprazole dose level, 30 mg o.a.d. already increased
      intragastric pH considerably. This effect was even enhanced by increase of the
      lansoprazole dose as assessed by mean pH as well as percentage of time spent
      above different pH values. The increase in effect with lansoprazole dose
      increment from 30 mg b.i.d. to 60 mg b.i.d. was only very small. The time spent
      at pH values above or equal to 3 after b.i.d. administration was slightly higher
      with all lansoprazole dose levels compared to omeprazole. The time spent at
      intragastric pH values above or equal to 5 after b.i.d. oral administration of 30
      mg, 45 mg and 60 mg lansoprazole was comparable to that observed after b.i.d.
      oral administration of 20 mg omeprazole, so that it may be recommended to use
      lansoprazole 30 mg b.i.d. as a treatment equivalent to omeprazole 20 mg b.i.d.
      for eradication of Helicobacter pylori in combination with antibiotics.

PMID- 8577213
TI  - [Transjugular intrahepatic portosystemic shunt (TIPS): survived the trial by
      fire?].

PMID- 8577214
TI  - [Preventing transmission of infection in endoscopy: hygienic maintainance of
      flexible endoscopes and measures for personal protection].
AB  - For prevention of transfer of infective agents by the contaminated endoscope the
      importance of thorough mechanical cleaning of the endoscope and adequate
      disinfection is stressed. Mode of action and side effects of liquid disinfectants
      as well as resistance of microorganisms (spores and some mycobacteria) to
      germicidal chemicals are mentioned. The different steps of disinfection
      procedures and potential causes of failure are discussed. Automatic disinfection
      systems are required for a higher degree of security of both patient and staff of
      the endoscopic unit. A regular control of the efficacy of the disinfection
      process is recommended and models for implementation are discussed. For
      prevention of occupationally acquired infection general precaution guidelines
      (use of gloves, prevention of needle-stick injuries) and vaccination programs are
      stressed.

PMID- 8577215
TI  - [Clinico-prognostic significance of partial seroconversion in chronic viral
      hepatitis B follow-up. Wartenbert Study (1974-1994), II].
AB  - 146 patients (62 female, 84 male) with chronic hepatitis B were regularly
      examined in 1 to 2 year intervals with an average follow-up period of 12 years
      (means). Each time patients were evaluated by physical examination, routine
      laboratory data, immunological and serological testing, ultrasonography, and
      laparoscopy and/or percutaneous liver biopsy. No patient of the study underwent
      immunosuppressive or antiviral treatment at any time. The average time data in
      years and months are given as the median value (mean). Frequency and date of
      seroconversion from HBeAg to anti-HBe after the first diagnosis of HBV-infection:
      in patients with chronic persistent hepatitis (CPH) in 79% of cases after 8
      years, in patients with chronic active hepatitis (CAH) in 72% of cases after 7
      years, and in patients with liver cirrhosis in 61% of cases after 9 years. The
      overall seroconversion rate in all patients with chronic hepatitis B amounted to
      68% 8.5 years after the first diagnosis of HBV-infection. Clinical and prognostic
      significance: The seroconversion from HBeAg to anti-HBe mostly led to substantial
      and sustained biochemical and histologic resolution of liver disease activity. In
      patients with CPH in 100% of cases after 15 months, in patients with CAH in 87%
      of cases after 17 months, and in patients with liver cirrhosis in 64% of cases
      after 2.5 years. 80% of these patients with seroconversion and histologic
      recovery remained HBV-DNA (PCR)-positive.

PMID- 8577216
TI  - [Initial clinical experiences with TIPS (transjugular intrahepatic portasystemic
      stent-shunt)].
AB  - 15 patients with predominantly alcoholtoxic liver cirrhosis (mean age 50 years; 8
      men and 7 women) were treated by the technically successful implantation of a
      transjugular portosystemic stent-shunt (TIPS) within a period of 1 year. The
      indications for TIPS implantation were the following: gastroesophageal bleedings
      in 12 cases (10 patients with recurrent variceal bleeding including 2 emergency
      cases with severe bleeding resistant to conventional therapy and 2 patients with
      exclusively gastral bleeding due to severe hypertensive gastropathy) and ascites
      resistant to conventional therapy in 3 cases. Portovenous pressure could be
      effectively reduced by mean of 37%. Within a mean observation period of 8 months
      13 patients including the emergency cases remained without recurrent bleeding.
      Duplexsonography showed patent stents. 1 patient suffered from an early recurrent
      bleeding due to occlusion of the stent-shunt. The estimation of liver function
      according to the Child-Pugh-classification showed only minor changes. Before TIPS
      9 patients were in class A, 4 in B, 2 in C; after TIPS 8 patients in A, 5 in B
      and 2 in C. Ascites resolved completely. Following TIPS all patients appeared to
      abstain from alcohol. After TIPS 5 from 14 surviving patients (36%) developed
      clinically manifest encephalopathy within the first 4-8 weeks (2 patients with
      previous episodes of encephalopathy, 2 other patients after withdrawal of
      lactulose). By enhanced conservative treatment (lactulose, paromomycine and
      protein restriction) encephalopathy could be overcome. 8 from 11 surviving
      patients investigated displayed characteristic MRI changes with an increased
      signal intensity in the basal ganglia (T1 weighted images). According to our
      preliminary results TIPS represents a new successful interventional regimen for
      the treatment of portal hypertension in selected cases.

PMID- 8577217
TI  - [Mesenteric panniculitis].
AB  - We report three cases of mesenteric panniculitis in which the disease took
      different courses. The first case clinically mimicked an acute diverticulitis and
      consequently laparotomy was performed. During this operation a large space
      occupying tumour was found in the lower abdomen. After resecting this tumour mass
      of uncertain classification (benign or malignant) a preternatural anus of sigmoid
      colon was formed. Histological exploration revealed mesenteric panniculitis. Six
      months later we restored continuity of large bowel by end-to-end anastomosis. No
      residues of the preexisting panniculitic alterations were seen. The second case
      concerned a female patient who again complained of discomfort after surgical
      treatment of colon carcinoma. We measured an elevated erythrocyte sedimentation
      rate and suspected a relapse of the malignant disease. Notwithstanding
      radiological and endoscopic diagnostics, the origin and classification of an
      intra-abdominal tumour could not be determined preoperatively. Laparoscopically
      we took a biopsy of the local mass, but a definite diagnosis was not found.
      Postoperatively undulant fever occurred, uninfluenced by cortisone treatment.
      Finally the patient died because of unstoppable hemorrhage under coagulopathy.
      Mesenteric panniculitis was identified as causative disease by autopsy.

PMID- 8577218
TI  - [Diverticulitis of the jejunum as a rare cause of acute gastrointestinal
      hemorrhage--diagnosis and therapy].
AB  - Small bowel diverticulosis is in contrast to large intestine diverticulosis an
      uncommon, acquired entity. In most cases it was found in duodenum and as a
      Meckel's diverticulum. Jejunal or ileal diverticulosis is a relatively rare
      disease. Although the majority of the patients do not require surgical treatment
      because of the absence of clinical signs, in 10% complications may necessitate
      small bowel resection. The clinical significance, diagnostic evaluation, and
      treatment of jejunal diverticular disease are reviewed.

PMID- 8577219
TI  - [Hepatic encephalopathy].

PMID- 8577220
TI  - [One week triple therapy for eradication of Helicobacter pylori infection: simple
      and effective].

PMID- 8577221
TI  - Antioxidant stoichiometry and the oxidative fate of vitamin E in peroxyl radical
      scavenging reactions.
AB  - Oxidation of R,R,R-alpha-tocopherol (vitamin E; TH) by peroxyl radicals generated
      from the azo initiator azobis(2,4-dimethylvaleronitrile) in acetonitrile, hexane,
      or in phospholipid liposomes yields 8a-(alkyldioxy)tocopherone adducts, 8a
      (hydroxy)tocopherone, and their hydrolysis product alpha-tocopherolquinone. TH
      oxidation also yields 4a,5-epoxy- and 7,8-epoxy-8a-(hydroperoxy)tocopherones and
      their respective hydrolysis products 2,3-epoxy-alpha-tocopherolquinone and 5,6
      epoxy-alpha-tocopherolquinone. Previous work indicates that the distribution of
      TH oxidation products varies with reaction environment. We investigated the
      dependence of antioxidant stoichiometry on TH oxidation product distribution for
      reactions in hexane, acetonitrile, and in phosphatidylcholine liposomes. Yields
      of 8a-substituted tocopherones were highest in hexane and lowest in
      phosphatidylcholine liposomes. In contrast, yields of epoxide products were
      highest in the liposome system and lowest in hexane. Yields of alpha
      tocopherolquinone were similar in all three systems. Antioxidant stoichiometry,
      measured by the inhibited autoxidation method, was approximately 2.0 peroxyl
      radicals trapped per TH consumed in acetonitrile and in liposomes. In hexane, a
      slightly larger stoichiometric factor of approximately 2.5 was measured. This
      may, in part, reflect the generation of more reactive alkoxyl radicals in hexane.
      The reaction environment thus markedly affects the balance between competing TH
      oxidation pathways but produces comparatively little effect on antioxidant
      stoichiometry. These results imply that competing reaction pathways contribute
      similarly to the antioxidant chemistry of TH.

PMID- 8577222
TI  - Cholesterol interaction with recombinant human sterol carrier protein-2.
AB  - The interaction of human recombinant sterol carrier protein-2 (SCP-2) with
      sterols was examined. Two independent ligand binding methods, Lipidex 1000
      binding of [3H]cholesterol and a fluorescent dehydroergosterol binding assay,
      were used to determine the affinity of SCP-2 for sterols. Binding analysis
      indicated SCP-2 bound [3H]cholesterol and dehydroergosterol with a Kd of 0.3 and
      1.7 microM, respectively, and suggested the presence of a single binding site.
      Phase fluorometry and circular dichroism were used to characterize the SCP-2
      sterol binding site. Alterations in dehydroergosterol lifetime, SCP-2 tryptophan
      lifetime, and SCP-2 tryptophan quenching by acrylamide upon cholesterol binding
      demonstrated a shielding of the SCP-2 tryptophan from the aqueous solvent by
      bound sterol. Differential polarized phase fluorometry revealed decreased SCP-2
      tryptophan rotational correlation time upon cholesterol binding. Circular
      dichroism of SCP-2 indicated that cholesterol elicited a small decrease in SCP-2
      alpha helical content. The data suggest that SCP-2 binds sterols with affinity
      consistent with a lipid transfer protein that may act either as an aqueous
      carrier or at a membrane surface to enhance sterol desorption.

PMID- 8577223
TI  - Molecular species of sphingomyelin in sphingomyelinase-sensitive and
      sphingomyelinase-resistant pools of HL-60 cells.
AB  - This study of sphingomyelin molecular species in undifferentiated and
      differentiated (granulocytic form) HL-60 cells demonstrated only minor
      differences in the distribution of species between the sphingomyelinase-sensitive
      and sphingomyelinase-resistant pools of sphingomyelin in these cells. The two
      most prominent species of sphingosine present in both the undifferentiated and
      differentiated cells were those containing 16:0 (slightly higher in the
      sphingomyelinase-resistant membranes) and 24:1 N-acyl moieties. Cell
      differentiation exerted little effect on the distribution of molecular species of
      sphingomyelin between the sphingomyelinase-sensitive and sphingomyelinase
      resistant pools in HL-60 cells, although the levels of N-palmitoyl sphinganine
      were significantly lower and the N-nervonoyl sphingosine higher in both pools
      from the differentiated cells. Our results indicate the same species of
      sphingomyelin, available at both the outer layer of the plasma membrane and inner
      layer of the plasma membrane (plus intracellular membranes) of HL-60 cells, serve
      as precursors for generation of the ceramides that participate in signal
      transduction processes initiated by cell activation.

PMID- 8577224
TI  - Lipid changes in HL-60 cells on differentiation into macrophages by treatment
      with a phorbol ester.
AB  - We studied changes in lipid composition of human promyelocytic leukemia cells (HL
      60) on differentiation to the macrophage/monocytic lineage by treatment with the
      phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate. Differentiation was
      accompanied by: (i) a decrease in the level of phospholipids; (ii) a greater
      amount of triacylglycerols; (iii) an increase in 1-alk-1'-enyl-2-acyl- and 1
      alkyl-2-acyl-sn-glycero-3-phosphoethanolamine and a decrease in 1-alkyl-2-acyl-sn
      glycero-3-phosphocholine; and (iv) an increase in the level of arachidonic acid
      in ethanolamine phospholipids. The increased levels of ether-linked lipids and of
      arachidonic acid in ethanolamine phospholipids are consistent with an enhanced
      biosynthesis of platelet-activating factor and eicosanoids, which are
      particularly important in the macrophage function.

PMID- 8577225
TI  - Pathogenesis of oleic acid-induced lung injury in the rat: distribution of oleic
      acid during injury and early endothelial cell changes.
AB  - Oleic acid-induced lung injury, a well-described laboratory model for acute
      pulmonary injury in the rat and other species, causes morphologic and cellular
      changes similar to human adult respiratory distress syndrome (ARDS). Experiments
      were performed to test the hypothesis that the initial event of oleic acid lung
      injury is damage of the pulmonary vascular endothelium by oleic acid, with
      subsequent pulmonary damage and inflammation. Oleic acid levels were followed in
      the lung and other tissues by measuring accumulation of 14C-oleic acid; the
      direct effects of oleic acid and other fatty acids on rat endothelial cells,
      alveolar type II cells, and hepatocytes in culture were determined. Lung tissue
      from treated rats was also examined by light and electron microscopy for evidence
      of endothelial cell damage. At 30 min after injury, oleic acid reached high
      concentrations in lung tissue as demonstrated by presence of radiolabel (3.24 x
      10(-6) moles per gram of tissue), with counts in the lung nearly an order of
      magnitude greater than in any other organ measured. Oleic acid was present in the
      lung mostly as free fatty acid (85%), and was also present in the alveolar fluid
      supernatants, rather than being cell-associated (1.7 x 10(-7) moles vs. 1.1 x 10(
      8) moles at 30 min). Oleic acid was toxic to endothelial cells after one minute
      of exposure at concentrations of 5 x 10(-4) M and above. Electron microscopy
      showed endothelial cell changes as early as 10 min after induction of injury in
      vivo, including the presence of endothelial cell blebbing.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8577226
TI  - Effect of low levels of dietary fish oil on fatty acid desaturation and tissue
      fatty acids in obese and lean rats.
AB  - The effect of very low levels of dietary long-chain n-3 fatty acids on delta 6
      desaturation of linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3), and
      on delta 5 desaturation of dihomo-gamma-linolenic acid (20:3n-6), in liver
      microsomes and its influence on tissue fatty acids were examined in obese and
      lean Zucker rats and in Wistar rats. Animals fed for 12 wk a balanced diet
      containing ca. 200 mg of long-chain polyunsaturated n-3 fatty acids per 100 g of
      diet were compared to those fed the same amount of alpha-linolenic acid. Low
      amounts of long-chain n-3 fatty acids greatly inhibited delta 6 desaturation of
      18:2n-6 and delta 5 desaturation of 20:3n-6, while delta 6 desaturation of 18:3n
      3 was not inhibited in Zucker rats and was even stimulated in Wistar rats.
      Inhibition of the biosynthesis of long-chain n-6 fatty acids was reflected in a
      decrease in arachidonic acid (20:4n-6) content of serum lipids when fasting, and
      also in the phospholipid fatty acids of liver microsomes. On the contrary, heart
      and kidney phospholipids did not develop any decrease in 20:4n-6 during fish oil
      ingestion. Docosahexaenoic acid (22:6n-3), present in the dietary fish oil, was
      increased in serum lipids and in liver microsome, heart, and kidney
      phospholipids.

PMID- 8577227
TI  - Thyroid hormone is required for dietary fish oil to induce hypersecretion of
      biliary cholesterol in the rat.
AB  - In the rat, both fish oil diet and thyroid hormone replacement are reported to
      augment bile cholesterol secretion out of proportion to bile flow or secretion of
      other bile lipids. We sought common mechanisms for these effects and evaluated
      the role of phospholipid fatty acid composition in the process. Methimazole
      treated hypothyroid rats were fed low-fat chow or chow supplemented with 10% corn
      oil or fish oil, and were studied before and after thyroid hormone treatment.
      Serum, hepatic, and bile lipids were measured, phospholipid fatty acid
      composition determined, and hepatic 3-hydroxy-3-methylglutaryl CoA reductase
      activity assayed. Fish oil diet stimulated cholesterol secretion into bile only
      after thyroid hormone was given, and this action was synergistic with that of
      thyroid hormone. Reduced serum cholesterol in fish oil-treated rats was
      associated with increased biliary cholesterol secretion and diminished hepatic
      cholesterol content. This suggests that augmented biliary cholesterol secretion
      may contribute to the fish oil-induced reduction of serum cholesterol. No
      definite relationship between hepatic or biliary phospholipid fatty acid
      composition and biliary secretion was apparent, although high bile cholesterol
      secretion was associated with a low percentage of hepatic and bile phospholipid
      linoleic acid.

PMID- 8577228
TI  - Cholestyramine alters the lipid and energy metabolism of chicks fed dietary
      medium- or long-chain triacylglycerol.
AB  - The effects of cholestyramine, a bile acid binding polymer, on the lipid and
      energy metabolism of chicks given dietary medium-chain triacylglycerol (MCT) or
      long-chain triacylglycerol (LCT) were investigated. Chicks (from 8 to 17 days of
      age) were fed diets containing MCT or LCT at 200 g oil/kg diet with or without 2%
      cholestyramine under equalized feeding conditions. An adjusted LCT diet was
      formulated in order to supply another group with daily nutrients and dietary
      metabolizable energy (ME) equal to MCT groups, except for corn starch. ME intakes
      of chicks given MCT or LCT diets were reduced by cholestyramine; consequently,
      fat and energy retention was reduced, though the reduction was more drastic in
      chicks fed LCT. This was caused by a change in amounts of the fecal excretion of
      fat and bile acids. Cholestyramine enhanced the excretion of octanoic acid (8:0)
      in the feces, which suggests that bile acids are needed for 8:0 absorption.
      Cholestyramine affects the utilization of dietary MCT and LCT by lowering fat and
      energy retention in chicks. However, the effect of cholestyramine on MCT
      utilization was smaller than its effect on utilization of LCT.

PMID- 8577229
TI  - Resistant starch is more effective than cholestyramine as a lipid-lowering agent
      in the rat.
AB  - Amylase-resistant starch (RS) represents a substrate for the bacterial flora of
      the colon, and the question arises as whether RS shares with soluble fibers
      common mechanisms for their lipid-lowering effects. It is uncertain whether a
      cholesterol-lowering effect depends basically on an enhanced rate of steroid
      excretion or whether colonic fermentations also play a role in this effect. In
      the present study, the effect of RS (25% raw potato starch), of a steroid
      sequestrant (0.8% cholestyramine), or both were compared on bile acid excretion
      and lipid metabolism in rats fed semipurified diets. RS diets led to a marked
      rise in cecal size and the cecal pool of short-chain fatty acids (SCFA), as well
      as SCFA absorption; cholestyramine did not noticeably affect cecal fermentation.
      Whereas cholestyramine was particularly effective at enhancing bile acid
      excretion, RS was more effective in lowering plasma cholesterol (-32%) and
      triglycerides (-29%). The activity of 3-hydroxy-3-methylglutaryl-CoA reductase
      was increased fivefold by cholestyramine and twofold by RS. This induction in
      rats fed RS diets was concomittant to a depressed fatty acid synthase activity.
      In rats fed the RS diet, there was a lower concentration of cholesterol in all
      lipoprotein fractions, especially the (d = 1.040-1.080) fraction high-density
      lipoprotein (HDL1), while those fed cholestyramine had only a significant
      reduction of HDL1 cholesterol. In contrast to cholestyramine, RS also depressed
      the concentration of triglycerides in the triglyceride-rich lipoprotein
      fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8577230
TI  - Hydrophilic bile acids: prevention and dissolution experiments in two animal
      models of cholesterol cholelithiasis.
AB  - The effects of beta-muricholic acid and hyocholic acid on cholesterol
      cholelithiasis were examined in two animal models. The following experiments were
      carried out: A) In a gallstone prevention study, prairie dogs were fed the
      lithogenic diet with or without 0.1% beta-muricholic or 0.1% hyocholic acid for
      eight weeks. B) In a second prevention study, hamsters were fed the lithogenic
      diet with or without 0.1% beta-muricholic acid or 0.1% hyocholic acid for six
      weeks. C) In a gallstone dissolution study, hamsters were fed the lithogenic diet
      for six weeks to induce stones; stone dissolution was examined during
      administration of a cholesterol-free purified diet with or without 0.1% beta
      muricholic acid or 0.1% hyocholic acid. In the prevention study in prairie dogs
      (A), both bile acids failed to prevent stone formation, the cholesterol
      saturation index of bile was 0.89 in the lithogenic controls, remained unchanged
      with hyocholic acid and increased to 1.52 in the beta-muricholic acid group. In
      the prevention study in hamsters (B), beta-muricholic acid completely inhibited
      the cholesterol cholelithiasis (0% stone incidence); the cholesterol saturation
      index of bile was 1.78 (compared to lithogenic controls, 1.37). Hyocholic acid
      reduced stone incidence to 16% with a cholesterol saturation index of 0.98. In
      the dissolution study in hamsters (C), preexisting cholesterol gallstones were
      not dissolved by either hydrophilic bile acid after feeding these bile acids for
      an additional six weeks; at the end of the experiment, the cholesterol saturation
      indices were below unity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8577231
TI  - Continuous spectrophotometric assay of conjugated bile acid hydrolase.
AB  - Conjugated bile acid hydrolase (CBAH) refers to a class of enzymes which catalyze
      the cleavage of the amino acid moieties from conjugated bile acids. These enzymes
      are significant because of their role in providing substrates for further
      microbial metabolism in the gastrointestinal tract. They also are used in
      research laboratories for the deconjugation of bile acids prior to structural
      analyses. A continuous spectrophotometric assay for CBAH activity was developed
      using a conjugate of cholic acid and the chromophore, 5-amino-2-nitro-benzoic
      acid. The free chromophore is detected by virtue of its absorbance at 410 nm. The
      CBAH from Clostridium perfringens displayed a Km for this substrate of 120
      microM. These results demonstrate that this new compound functions as an
      effective substrate of the enzyme and forms the basis for a convenient and rapid
      method to monitor CBAH activity.

PMID- 8577232
TI  - Use of gas chromatography/isotope ratio-mass spectrometry to study triglyceride
      metabolism in humans.
AB  - The study of triglyceride (TG) metabolism using stable isotope tracers would be
      facilitated by being able to detect low 13C enrichment. To meet this goal, we
      developed a gas chromatography/isotope ratio-mass spectrometry technique to
      measure the enrichment of palmitate in nonesterified fatty acids (NEFA) and TG as
      its methyl derivative. This method allows accurate and reproducible measurements
      of enrichment as low as 0.009 mole percent excess (MPE), in a range between 0
      0.65 MPE. The usefulness of this method is shown by two studies of lipid
      metabolism in human beings. First, we studied the metabolic fate of an oral TG
      load labeled with [1,1,1-13C3]tripalmitin. Labeled palmitate appeared
      concurrently in plasma NEFA and TG, and four hours after the load, the labeling
      was higher in NEFA than in TG (MPE NEFA: 1.53 +/- 0.31 vs. MPE TG: 0.78 +/- 0.06,
      P < 0.05). In a second study, the hepatic reesterification of NEFA was estimated
      by measuring the appearance of infused [1-13C]palmitate in circulating TG. The
      estimated contribution of plasma NEFA to circulating TG increased to a maximum of
      22%. Thus, gas chromatography/isotope ratio-mass spectrometry appears to be a
      useful tool for future studies of lipid metabolism in humans.

PMID- 8577233
TI  - Microscale synthesis of phosphatidyl-[3H]choline from 1,2-diacylglycerol.
      Assessment of isomerization by reversed-phase high-performance liquid
      chromatography.
AB  - The synthesis of rac-1-palmitoyl-2-oleoylglycero-3-phospho-[3H]choline of high
      specific activity was carried out on a microscale by making 7 mumol of rac-1
      palmitoyl-2-oleoylglycerol react first with an equimolar amount of POCl3 and then
      of [3H]choline. After purification by thin-layer chromatography and normal-phase
      high-performance liquid chromatography and normal-phase high-performance liquid
      chromatography (HPLC), the yield of the synthesis of [3H]phosphatidylcholine (120
      microCi/mumol) was 22%. rac-1-Palmitoyl-2-oleoylglycerol was purified before use
      by reversed-phase HPLC under conditions which were nonisomerizing and allowed the
      separation of 1,2- and 1,3-isomers of diacylglycerol. Ethanol, but not benzene,
      was shown to cause isomerization of long-chain diacylglycerol and, therefore, was
      not used for drying the substrate before reaction. A rapid and complete
      separation of 1,2- and 1,3-isomers of long-chain phosphatidylcholine was obtained
      by reversed-phase HPLC using 20 mM choline chloride in
      methanol/acetonitrile/water (50:50:1, by vol) isocratically as the mobile phase.
      Under these conditions, analysis of the synthesized rac-1-palmitoyl-2
      oleoylglycero-3-phospho-[3H]choline showed a total absence of 1,3-isomer.

PMID- 8577234
TI  - Interplay between mycoplasmas and host target cells.
AB  - The infectious pattern of mycoplasmas (Mycoplasma penetrans, Mycoplasma
      pneumoniae and Mycoplasma genitalium) in mammalian cells was examined using
      confocal microscopy and flow cytometry combined with cell fractionation and
      mycoplasma viability determinations. Within 2 h postinfection mycoplasmas
      parasitize cell surfaces, enter the intracellular spaces and locate throughout
      the cytoplasmic and perinuclear regions. These mycoplasmas can be cultivated from
      cytoplasmic and nuclear fractions 96 h later and continue to persist
      intracellularly for at least 7 days, suggesting a much more active intracellular
      role for mycoplasmas than had been considered previously.

PMID- 8577235
TI  - The pentameric structure of IgM is necessary to enhance opsonization of
      Bacteroides thetaiotaomicron and Bacteroides fragilis via the alternative
      complement pathway.
AB  - Studies were conducted to investigate the mechanisms by which natural IgM
      antibodies act together with the alternative complement pathway to promote
      opsonization and adherence of encapsulated Bacteroides thetaiotaomicron and
      Bacteroides fragilis to polymorphonuclear leukocytes (PMN). A model system
      consisting of the six isolated proteins of the alternative pathway was used. A
      comparison of the opsonic effects of pentameric and monomeric forms of isolated
      normal IgM demonstrated that, although the monomeric form bound to Bacteroides as
      effectively as the pentameric form and promoted complement deposition to the same
      extent, it was unable to enhance alternative pathway-dependent opsonization and
      adherence of Bacteroides to PMN. When opsonization was performed in two steps
      with pentameric IgM added either before or after alternative pathway components,
      a marked enhancement of adherence to PMN was observed only in the former case,
      suggesting IgM must act prior to complement to be effective. Electron microscopic
      studies demonstrated that, when added with complement, pentameric IgM, but not
      monomeric IgM, stabilized the bacterial capsule to the dehydration in
      dimethylformamide used for embedding in Lowicryl K4M. A strong correlation was
      observed between capsular stability and ability to be bound by PMN. The results
      suggest that pentameric IgM alters the structure of capsular components, perhaps
      through crosslinking, and this is in turn facilitates interaction of C3bi and C3b
      with CR3 and CR1, their respective receptors on PMN.

PMID- 8577236
TI  - Construction and characterization of recombinant Vibrio cholerae strains carrying
      heterologous genes encoding non-01 antigen or cholera enterotoxin.
AB  - In an attempt to study the effect of heterologous genes on the virulence of
      Vibrio cholerae 01 and non-01, rfb genes encoding biosynthesis of non-01 antigens
      were introduced by homologous recombination into the chromosome of V. cholerae 01
      strain 569B (serotype Inaba, biotype classical). Recombinant strains were
      obtained which were not agglutinated with the diagnostic cholera 01 antiserum and
      were not sensitive to the cholera diagnostic bacteriophage, but produced as much
      cholera toxin as 569B and were highly virulent in the infant rabbit
      intraintestinal injection model. These data indicate that the rfb genes from the
      studied V. cholerae non-01 did not alter the virulence phenotype of V. cholerae
      01. In contrast, cloned ctxAB genes from V. cholerae 01 encoding cholera toxin
      introduced into a non-pathogenic strain lead to efficient secretion of cholera
      toxin but to only low virulence in the infant rabbit model.

PMID- 8577237
TI  - Persistent infection of mice with Pichinde virus associated with failure to
      thrive.
AB  - Intracranial inoculation of neonatal mice of certain inbred strains with Pichinde
      virus has been found to be fatal, but Balb/c neonates survive such infection.
      Survival of Balb/c mice after neonatal inoculation was not linked to the major
      histocompatability complex. Virus was gradually cleared in surviving Balb/c mice
      but could be detected in the brain and kidneys for up to 9 months after
      infection. These animals were not immunologically tolerant but exhibited high
      antibody titers to viral antigens. MHC restricted cytotoxic T cell activity was
      also demonstrable in persistently infected mice following challenge with high
      titered virus. Pathological changes consistent with glomerulonephritis were
      observed in the kidneys and surviving mice were runted compared to normals. This
      model differs from the widely studied persistent infection of mice with
      lymphocytic choriomeningitis virus (LCMV) and provides a unique model for the
      study of the genetics of resistance to viral infection, mechanisms of persistence
      and pathological processes in chronic viral infections.

PMID- 8577238
TI  - Correlation of epithelial cell invasiveness of group B streptococci with clinical
      source of isolation.
AB  - Neonatal infections caused by Group B streptococci (GBS) may lead to pneumonia,
      sepsis, or meningitis indicating that GBS are able to invade tissues and enter
      the bloodstream from infected sites. In this study, we showed that the tissue
      invasiveness of GBS may be related to their ability to invade epithelial cells in
      vitro by correlating the degree of GBS invasion of cultured human respiratory
      epithelial cells with the clinical source of isolation. Among 77 isolates tested,
      those from invasive infections of neonates and adults were significantly (P <
      0.001) more invasive than those from vaginal carriers and colonised neonates
      without clinical symptoms. Furthermore, isolates from the blood were more
      invasive (P < 0.05) than those from other sites. GBS invasion seemed to be
      mediated by bacterial surface proteins since trypsin treatments of streptococci
      significantly reduced their invasion into epithelial cells and invasiveness was
      not limited to a certain capsular serotype. The two major GBS surface protein
      antigens c and R, however, were not involved in the invasion process. These
      results indicate that in vitro invasion of cultured human cells reflects the in
      vivo invasive property of GBS and involves bacterial surface components different
      from known virulence factors such as capsule or protein antigens c and R.

PMID- 8577239
TI  - Iron mediates Trichomonas vaginalis resistance to complement lysis.
AB  - Trichomonas vaginalis, a sexually transmitted disease agent in humans, is readily
      lysed by activation of the alternative complement pathway. The parasite became
      resistant following growth in medium supplemented by iron compared to parasites
      grown in medium depleted of iron, which were readily killed by complement. The
      resistance to complement was dependent on iron concentration while divalent
      cations other than iron were ineffective, showing specific regulation of this
      property by iron. Lactoferrin, but not transferrin, rendered low-iron-parasites
      resistant to complement lysis, reinforcing the in vivo modulation by a known
      source of iron for this parasite. Pretreatment of high-iron, complement-resistant
      parasites with proteinase inhibitors resulted in lysis by complement, indicating
      that resistance was likely due to proteinase degradation of C3 on the trichomonal
      surface.

PMID- 8577240
TI  - BLAST 1995: international conference on bacterial locomotion and signal
      transduction.

PMID- 8577241
TI  - Hypothesis: chromosome separation in Escherichia coli involves autocatalytic gene
      expression, transertion and membrane-domain formation.
AB  - To explain how daughter chromosomes are separated into discrete nucleoids and why
      chromosomes are partitioned with pole preferences, I propose that differential
      gene expression occurs during DNA replication in Escherichia coli. This
      differential gene expression means that the daughter chromosomes have different
      patterns of gene expression and that cell division is not a simple process of
      binary fission. Differential gene expression arises from autocatalytic gene
      expression and creates a separate proteolipid domain around each developing
      chromosome via the coupled transcription-translation-insertion of proteins into
      membranes (transertion). As these domains are immiscible, daughter chromosomes
      are simultaneously replicated and separated into discrete nucleoids. I also
      propose that the partitioning relationship between chromosome age and cell age
      arises because the poles of cells have a proteolipid composition that favours
      transertion from one nucleoid rather than from the other. This hypothesis forms
      part of an ensemble of related hypotheses which attempt to explain cell division,
      differentiation and wall growth in bacteria in terms of the physical properties
      and interactions of the principal constituents of cells.

PMID- 8577242
TI  - Colicin import and pore formation: a system for studying protein transport across
      membranes?
AB  - Pore-forming colicins are a family of protein toxins (M(r) 40-70 kDa) produced by
      Escherichia coli and related bacteria. They are bactericidal by virtue of their
      ability to form ion channels in the inner membrane of target cells. They provide
      a useful means of studying questions such as toxin action, polypeptide
      translocation across and into membranes, voltage-gated channels and receptor
      function. These colicins bind to a receptor in the outer membrane before being
      translocated across the cell envelope with the aid of helper proteins that belong
      to nutrient-uptake systems and the so-called 'Tol' proteins, the function of
      which has not yet been properly defined. A distinct domain appears to be
      associated with each of three steps (receptor binding, translocation and
      formation of voltage-gated channels). The Tol-dependent uptake pathway is
      described here. The structures and interactions of TolA, B, Q and R have by now
      been quite clearly defined. Transmembrane alpha-helix interactions are required
      for the functional assembly of the E. coli Tol complex, which is preferentially
      located at contact sites between the inner and outer membranes. The number of
      colicin translocation sites is about 1000 per cell. The role and the involvement
      of the OmpF porin (with colicins A and N) have been described in a recent study
      on the structural and functional interactions of a colicin-resistant mutant of
      OmpF. The X-ray crystal structure of the channel-forming fragment of colicin A
      and that of the entire colicin la have provided the basis for biophysical and
      site-directed mutagenesis studies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8577243
TI  - Treponema pallidum and the quest for outer membrane proteins.
AB  - Treponema pallidum, the syphilis spirochaete, has a remarkable ability to evade
      the humoral and cellular responses it elicits in infected hosts. Although
      formerly attributed to the presence of an outer coat comprised of serum proteins
      and/or mucopolysaccharides, current evidence indicates that the immuno
      evasiveness of this bacterium is largely the result of its unusual molecular
      architecture. Based upon a combination of molecular, biochemical, and
      ultrastructural data, it is now believed that the T. pallidum outer membrane (OM)
      contains a paucity of poorly immunogenic transmembrane proteins ('rare outer
      membrane proteins') and that its highly immunogenic proteins are lipoproteins
      anchored predominantly to the periplasmic leaflet of the cytoplasmic membrane.
      The presence in the T. pallidum OM of a limited number of transmembrane proteins
      has profound implications for understanding syphilis pathogenesis as well as
      treponemal physiology. Two major strategies for molecular characterization of
      rare outer membrane proteins have evolved. The first involves the identification
      of candidate OM proteins as fusions with Escherichia coli alkaline phosphatase.
      The second involves the characterization of candidate OM proteins identified in
      outer membranes isolated from virulent T. pallidum. Criteria to define candidate
      OM proteins and for definitive identification of rare OM proteins are proposed as
      a guide for future studies.

PMID- 8577244
TI  - Virus DNA packaging: the strategy used by phage lambda.
AB  - Phage lambda, like a number of other large DNA bacteriophages and the
      herpesviruses, produces concatemeric DNA during DNA replication. The concatemeric
      DNA is processed to produce unit-length, virion DNA by cutting at specific sites
      along the concatemer. DNA cutting is co-ordinated with DNA packaging, the process
      of translocation of the cut DNA into the preformed capsid precursor, the prohead.
      A key player in the lambda DNA packaging process is the phage-encoded enzyme
      terminase, which is involved in (i) recognition of the concatemeric lambda DNA;
      (ii) initiation of packaging, which includes the introduction of staggered nicks
      at cosN to generate the cohesive ends of virion DNA and the binding of the
      prohead; (iii) DNA packaging, possibly including the ATP-driven DNA
      translocation; and (iv) following translocation, the cutting of the terminal cosN
      to complete DNA packaging. To one side of cosN is the site cosB, which plays a
      role in the initiation of packaging; along with ATP, cosB stimulates the
      efficiency and adds fidelity to the endonuclease activity of terminase in cutting
      cosN. cosB is essential for the formation of a post-cleavage complex with
      terminase, complex I, that binds the prohead, forming a ternary assembly, complex
      II. Terminase interacts with cosN through its large subunit, gpA, and the small
      terminase subunit, gpNu1, interacts with cosB. Packaging follows complex II
      formation. cosN is flanked on the other side by the site cosQ, which is needed
      for termination, but not initiation, of DNA packaging. cosQ is required for
      cutting of the second cosN, i.e. the cosN at which termination occurs. DNA
      packaging in lambda has aspects that differ from other lambda DNA transactions.
      Unlike the site-specific recombination system of lambda, for DNA packaging the
      initial site-specific protein assemblage gives way to a mobile, translocating
      complex, and unlike the DNA replication system of lambda, the same protein
      machinery is used for both initiation and translocation during lambda DNA
      packaging.

PMID- 8577245
TI  - Functional implications of the expression of PilC proteins in meningococci.
AB  - Multiple forms of PilC were found in Neisseria meningitidis (Nm) strains isolated
      from the oropharynx, blood or cerebrospinal fluid expressing either Class I or
      Class II pili. PilC expression was observed less frequently in case as opposed to
      carrier isolates. Moreover, PilC and pili were not always co-expressed. Several
      heavily piliated strains had no detectable PilC protein as determined by Western
      blotting using an antiserum previously used to detect such proteins in adhesive
      variants (Nassif et al., 1994). Serogroup B strain MC58 produced large numbers of
      pili, but expressed barely detectable amounts of PilC. A clonal variant of this
      strain with increased expression of PilC concurrently exhibited increased
      adherence to Chang conjunctival epithelial cells and human umbilical vein
      endothelial cells (Huvecs), but with more rapid binding to the former. No
      alteration in pilin sequence occurred in this variant, suggesting the involvement
      of PilC in increased adhesion. A Pil- backswitcher isolated from the hyper
      adherent variant was PilC+ but was non-adherent, indicating that any PilC
      adherence function requires pilus expression. Parental variant (low PilC)
      produced pili in bundles that were easily detached from the bacterial surface and
      were frequently associated with Huvec surfaces after bacteria had been sheared
      off, but pili infrequently replaced bacteria during infection with the PilC
      expressing variant. The hyper-adherent variant, which appeared to produce
      morphologically distinct pilus bundles, was able to withstand considerable
      shearing force and remained firmly attached to Huvecs. This raises the
      possibility that the observed hyper-adherence may arise from better anchorage of
      pili to the bacterial surface in addition to increased adhesion to some host cell
      surfaces.

PMID- 8577247
TI  - Regulation of ptsH and ptsI gene expression in Streptococcus salivarius ATCC
      25975.
AB  - The transcriptional regulation of the Streptococcus salivarius ptsH and ptsI
      genes coding for the general energy-coupling proteins HPr and enzyme I of the
      phosphoenolpyruvate:sugar phosphotransferase system were investigated. These
      genes form an operon with the gene order ptsH-ptsI. Three distinct mRNA species
      were detected: a 0.5 kb transcript specific for ptsH, and two long transcripts
      (2.2 and 2.4 kb) covering the whole pts operon. Transcription of all these mRNAs
      initiated at the same nucleotide located 9 bp downstream from a promoter located
      immediately upstream from the ptsH gene. The presence of a high-energy stem-loop
      structure (T0) located at the beginning of ptsI was responsible for the premature
      transcription termination generating the 0.5 kb ptsH-specific transcript. The
      long transcripts ended in the poly(U) region of two rho-independent-like
      terminators (T1 and T2) at the 3' end of ptsI. Studies with a 2-deoxyglucose
      resistant spontaneous mutant of S. salivarius (L26) that produces an HPr-EI
      fusion protein suggest that the regulation of HPr and EI expression involves
      transcriptional as well as translational mechanisms.

PMID- 8577246
TI  - The Cryptococcus neoformans GAL7 gene and its use as an inducible promoter.
AB  - A Cryptococcus neoformans galactose auxotroph was created by ultraviolet light
      mutagenesis and complemented with a C. neoformans genomic library. The translated
      sequence of the complementing DNA revealed a high degree of similarity to a
      number of UDP glucose-D-galactose-1-phosphate uridylyltransferases. Expression of
      C. neoformans GAL7 mRNA followed a pattern similar to Saccharomyces cerevisiae
      expression; it was first observed within 2.5 min of induction and fully induced
      by 30 min. The gene was completely repressed in the presence of glucose. The GAL7
      promoter was isolated and used to construct a promoter cassette. Two genes were
      tested in this cassette for galactose regulation by creating GAL7 promoter
      fusions with their coding regions. MF alpha, which encodes a pheromone, was found
      to produce filaments only in transformants that were induced by galactose. A
      second gene, beta-glucuronidase (gusA), which is a commonly used reporter gene,
      was tested and also found to be expressed. When the GAL7p::GUS fusion was used to
      quantify inducibility of the GAL7 promoter, the level of enzyme activity was at
      least 500-fold greater for cells grown in galactose than for cells grown in
      glucose. The GAL7 promoter is the first inducible promoter characterized in C.
      neoformans and the GUS gene is the first heterologous gene shown to be expressed
      in this yeast pathogen.

PMID- 8577248
TI  - A central domain of Rhizobium NodE protein mediates host specificity by
      determining the hydrophobicity of fatty acyl moieties of nodulation factors.
AB  - Previously, we have shown that the nodE gene is a major determinant of the
      difference in host range between Rhizobium leguminosarum biovars viciae and
      trifolii. A new genetic test system for stringent functional analysis of nodE
      genes was constructed. By testing chimeric nodE genes constructed by the exchange
      of polymerase chain reaction (PCR)-generated restriction cassettes, we show that
      a central domain, containing only 44 non-conserved amino acid residues,
      determines the host specificity of the NodE protein (401 amino acid residues).
      Mass spectrometric analysis of the lipo-chitin oligosaccharides (LCOs) produced
      by the new test strain containing the biovar viciae nodE gene shows that
      molecules containing a polyunsaturated C18:4 (trans-2, trans-4, trans-6, cis-11
      octadecatetraenoic) fatty acyl moiety are produced, as is the case for wild-type
      R. leguminosarum bv. viciae. The LCOs determined by the biovar trifolii nodE
      gene, which was overproduced in our test strain, carry C18:2 and C18:3 fatty acyl
      chains containing two or three conjugated trans double bonds, respectively.
      Therefore, the main difference between the nodE-determined LCOs of biovar viciae
      and trifolii in this system is the presence or absence of one cis double bond,
      resulting in the very different hydrophobicity of the LCOs. Using a newly
      developed spot application assay, we show that the C18:2- and C18:3-containing
      LCOs are able to induce the formation of nodule primordia on roots of Trifolium
      pratense. On the basis of these and other recent results, we propose that the
      host range of nodulation of the R. leguminosarum biovars viciae and trifolii is
      determined by the degree of hydrophobicity of the polyunsaturated fatty acyl
      moieties of their LCOs, which is mediated by the host-specific central domain of
      the NodE protein.

PMID- 8577249
TI  - Molecular characterization of the lincomycin-production gene cluster of
      Streptomyces lincolnensis 78-11.
AB  - The lincomycin (LM)-production gene cluster of the overproducing strain
      Streptomyces lincolnensis 78-11 was cloned, analysed by hybridization, as well as
      by DNA sequencing, and compared with the respective genome segments of other
      lincomycin producers. The lmb/lmr gene cluster is composed of 27 open reading
      frames with putative biosynthetic or regulatory functions (lmb genes) and three
      resistance (lmr) genes, two of which, lmrA and lmrC, flank the cluster. A very
      similar overall organization of the lmb/lmr cluster seems to be conserved in four
      other LM producers, although the clusters are embedded in non-homologous genomic
      surroundings. In the wild-type strain (S. lincolnensis NRRL2936), the lmb/lmr
      cluster apparently is present only in single copy. However, in the industrial
      strain S. lincolnensis 78-11 the non-adjacent gene clusters for the production of
      LM and melanin (melC) both are duplicated on a large (0.45-0.5 Mb) fragment,
      accompanied by deletion events. This indicates that enhanced gene dosage is one
      of the factors for the overproduction of LM and demonstrates that large-scale
      genome rearrangements can be a result of classical strain improvement by
      mutagenesis. Only a minority of the putative Lmb proteins belong to known protein
      families. These include members of the gamma-glutamyl transferases (LmbA), amino
      acid acylases (LmbC), aromatic amino acid aminotransferases (LmbF),
      imidazoleglycerolphosphate dehydratases (LmbK), dTDP-glucose synthases (LmbO),
      dTDP-glucose 4,6-dehydratases (LmbM) and (NDP-) ketohexose (or ketocyclitol)
      aminotransferases (LmbS). In contrast to earlier proposals on the biosynthetic
      pathway of the C-8 sugar moiety (methylthiolincosaminide), this branch of the LM
      pathway actually seems to be based on nucleotide-activated sugars as precursors.

PMID- 8577250
TI  - The global regulatory protein FruR modulates the direction of carbon flow in
      Escherichia coli.
AB  - The Escherichia coli fructose repressor, FruR, is known to regulate expression of
      several genes concerned with carbon utilization. Using a previously derived
      consensus sequence for FruR binding, additional potential operators were
      identified and tested for FruR binding in DNA band migration retardation assays.
      Operators in the control regions of operons concerned with carbon metabolism
      bound FruR, while those in operons not concerned with carbon metabolism did not.
      In vivo assays with transcriptional lacZ fusions showed that FruR controls the
      expression of FruR operator-containing genes encoding key enzymes of virtually
      every major pathway of carbon metabolism. Moreover, a fruR null mutation altered
      the rates of utilization of at least 36 carbon sources. In general, oxidation
      rates for glycolytic substances were enhanced while those for gluconeogenic
      substances were depressed. Alignment of FruR operators revealed that the
      consensus sequence for FruR binding is the same for operons that are activated
      and repressed by FruR and permitted formulation of a revised FruR-binding
      consensus sequence. The reported observations indicate that FruR modulates the
      direction of carbon flow by transcriptional activation of genes encoding enzymes
      concerned with oxidative and gluconeogenic carbon flow and by repression of those
      concerned with fermentative carbon flow.

PMID- 8577251
TI  - The atxA gene product activates transcription of the anthrax toxin genes and is
      essential for virulence.
AB  - Bacillus anthracis plasmid pXO1 carries the structural genes for the three
      anthrax toxin proteins, cya (edema factor), lef (lethal factor), and pag
      (protective antigen). Expression of the toxin genes by B. anthracis is enhanced
      during growth under elevated levels of CO2. This CO2 effect is observed only in
      the presence of another pXO1 gene, atxA, which encodes a transactivator of
      anthrax toxin synthesis. Here we show that transcription of atxA does not appear
      to differ in cells grown in 5% CO2 compared with cells grown in air. Using a new
      efficient method for gene replacement in B. anthracis, we constructed an atxA
      null mutant in which the atxA-coding sequence on pXO1 is replaced with an omega
      km-2 cassette. Transcription of all three toxin genes is decreased in the absence
      of atxA. The pag gene possesses two apparent transcription start sites, P1 and
      P2; only transcripts with 5' ends mapping to P1 are decreased in the atxA-null
      mutant. Deletion analysis of the pag promoter region indicates that the 111 bp
      region upstream of the P1 site is sufficient for atxA-mediated activation of this
      transcript. The cya and lef genes each have one apparent start site for
      transcription. Transcripts with 5' ends mapping to these sites are not detected
      in the atxA-null mutant. The atxA-null mutant is avirulent in mice. Moreover, the
      antibody response to all three toxin proteins is decreased significantly in atxA
      null mutant-infected mice. These data suggest that the atxA gene product also
      regulates toxin gene expression during infection.

PMID- 8577252
TI  - Characterization of the pelL gene encoding a novel pectate lyase of Erwinia
      chrysanthemi 3937.
AB  - Erwinia chrysanthemi 3937 secretes five major isoenzymes of pectate lyases
      encoded by the pelA, pelB, pelC, pelD and pelE genes. Recently, a new set of
      pectate lyases was identified in E. chrysanthemi mutants deleted of those pel
      genes. We cloned the pelL gene, encoding one of these secondary pectate lyases of
      E. chrysanthemi 3937, from a genomic bank of a strain deleted of the five major
      pel genes. The nucleotide sequence of the region containing the pelL gene was
      determined. The pelL reading frame is 1275 bases long, corresponding to a protein
      of 425 amino acids including a typical amino-terminal signal sequence of 25 amino
      acids. Comparison of the amino acid sequences of PelL and the exo-pectate lyase
      PelX of E. chrysanthemi EC16 revealed a low homology, limited to 220 residues of
      the central part of the proteins. No homology was detected with other bacterial
      pectinolytic enzymes. Regulation of pelL transcription was analysed using gene
      fusion. As shown for the other pel genes, the transcription of pelL is dependent
      on various environmental conditions. It is induced by pectic catabolic products
      and affected by growth phase, temperature, iron starvation, osmolarity,
      anaerobiosis, nitrogen starvation and catabolite repression. Regulation of pelL
      expression appeared to be independent of the KdgR repressor, which controls all
      the steps of pectin catabolism. In contrast, the pecS gene, which is involved in
      regulation of the synthesis of the major pectate lyases and of cellulase, also
      appeared to be involved in pelL expression. The PelL protein is able to macerate
      plant tissue. This enzyme has a basic isoelectric point, presents an endo
      cleaving activity on polygalacturonate or partially methylated pectin, with a
      basic pH optimum and an absolute requirement for Ca2+. The pelL mutant displayed
      a reduced virulence on potato tubers and Saintpaulia ionantha plants,
      demonstrating the important role of this enzyme in soft-rot disease.

PMID- 8577253
TI  - Response of a yeast glycogen synthase gene to stress.
AB  - In the yeast Saccharomyces cerevisiae, glycogen synthase is encoded by two genes:
      GSY1 and GSY2. The activity of the enzymes increases as cultures enter the
      stationary phase of growth. Using a GSY2::lacZ fusion gene, we have demonstrated
      that the increase in glycogen synthase activity resulted, at least in part, from
      an increase in the level of the protein rather than simply from a change in its
      phosphorylation state. Northern blot analysis showed a parallel increase in the
      level of the GSY2 mRNA, which is consistent with transcriptional activation of
      GSY2. Deletion analysis identified three regions upstream of GSY2 which are
      involved in GSY2 expression: regions A (-390 to -347 relative to the start of
      translation), B (-252 to -209) and C (-209 to -167). Region A or C independently
      activated expression of GSY2. In contrast, region B alone yielded only modest
      expression. Expression of GSY2 is induced by growth to stationary phase, heat
      shock or nitrogen starvation. Response to these stressors is mediated by elements
      within regions A and C. These elements appear to be related to the stress
      response elements found in other stress-responsive genes.

PMID- 8577254
TI  - Substitution of two histidine residues in YadA protein of Yersinia enterocolitica
      abrogates collagen binding, cell adherence and mouse virulence.
AB  - The plasmid-encoded surface protein YadA of Yersinia enterocolitica mediates
      binding to diverse extracellular matrix (ECM) proteins, adherence to epithelial
      cell lines, resistance to complement lysis, autoagglutination, and is required
      for mouse virulence. Using site-directed mutagenesis we attempted to analyse the
      relationship between structural domains and functions of YadA. In a first
      approach we could abrogate collagen binding by chemical modification of histidyl
      residues of YadA protein. This result prompted us to substitute histidyl residues
      (His) of conserved regions of YadA protein of Y. enterocolitica O8 by tyrosine
      residues using site-directed mutagenesis. Substitution of His-156 and His-159
      (YadA-2 mutant) resulted in abrogation of binding to ECM proteins, of cell
      adherence, and in reduction of mouse virulence, whereas autoagglutination, serum
      complement resistance and oligomer formation remained unaffected. A striking
      result was obtained from the orogastric mouse-infection model: the YadA-2 mutant
      retained the ability to colonize the small intestine and to invade and multiply
      within the Peyer's patches but was impaired in colonizing mesenteric lymph nodes
      and spleen in comparison to the wild-type strain.

PMID- 8577255
TI  - Cloning and characterization of a bradyzoite-specifically expressed gene
      (hsp30/bag1) of Toxoplasma gondii, related to genes encoding small heat-shock
      proteins of plants.
AB  - Stage conversion between the tachyzoite and bradyzoite forms of the protozoan
      parasite Toxoplasma gondii is an important aspect in the pathogenesis of
      toxoplasmosis. In an initial investigation of molecular regulation of stage
      conversion in T. gondii, we describe the cloning and characterization of a
      bradyzoite-specifically expressed gene (hsp30/bag1). Bradyzoite formation was
      induced in cell culture by alkaline pH, and this was followed by purification of
      this parasitic stage using magnetic cell sorting. A bradyzoite cDNA library was
      constructed by random amplification using the polymerase chain reaction.
      Screening with a bradyzoite-specific monoclonal antibody identified a reactive
      clone. The amino acid sequence derived from the 687 bp open reading frame showed
      similarity to the conserved C-terminal region of small heat-shock proteins from
      plants. Stage-specific expression of the naturally occurring 30 kDa antigen in
      bradyzoites was confirmed by polyclonal antisera generated against the
      recombinant antigen. Immunoelectron microscopy indicated a cytosolic location of
      this antigen in bradyzoites. The expression of HSP30/BAG1 seems to be regulated
      at the mRNA level, since reverse polymerase chain reaction using bradyzoite
      specific primers amplified transcripts in bradyzoites only, not in tachyzoites.

PMID- 8577256
TI  - Heterogeneous endolysins in Listeria monocytogenes bacteriophages: a new class of
      enzymes and evidence for conserved holin genes within the siphoviral lysis
      cassettes.
AB  - Listeria monocytogenes bacteriophages A118, A500 and A511 are members of three
      distinct phage groups with characteristic host ranges. Their endolysin (ply)
      genes were cloned and expressed in Escherichia coli as demonstrated by the
      conferred lytic phenotype when colonies of recombinant cells were overlaid with a
      lawn of Listeria cells. The nucleotide sequences of the cloned DNA fragments were
      determined and the individual enzymes (PLY118, 30.8 kDa; PLY500, 33.4 kDa;
      PLY511, 36.5 kDa) were shown to have varying degrees of homology within their N
      terminal or C-terminal domains. Transcriptional analysis revealed them to be
      'late' genes with transcription beginning 15-20 min post-infection. The enzymes
      were overexpressed and partially purified and their individual specificities
      examined. When applied exogenously, the lysins induced rapid lysis of Listeria
      strains from all species but generally did not affect other bacteria. Using
      hydrolysis of purified listerial cell walls, PLY511 was characterized as an N
      acetylmuramoyl-L-alanine amidase (EC 3.5.1.28) and shows homology in its N
      terminal domain to other enzymes of this type. In contrast, PLY118 and PLY500
      were shown to represent a new class of cell wall lytic enzymes which cleave
      between the L-alanine and D-glutamate residues of listerial peptidoglycan; these
      were designated as L-alanoyl-D-glutamate peptidases. These two enzymes share
      homology in the N-terminal domain which we propose determines hydrolytic
      specificity. Highly conserved holin (hol) gene sequences are present upstream of
      ply118 and ply500. They encode proteins of structural similarity to the product
      of phage lambda gene S, and are predicted to be membrane proteins which form
      pores to allow access of the lysins to their peptidoglycan substrates. This
      arrangement of conserved holin genes with downstream lysin genes among the
      siphoviral lysis cassettes explains why the cytoplasmic endolysins alone are not
      lethal, since they require a specific transport function across the cell
      membrane.

PMID- 8577257
TI  - Subcellular localization and topology of the K88 usher FaeD in Escherichia coli.
AB  - The subcellular localization of the K88 usher FaeD was studied in Escherichia
      coli whole cells by using isopycnic sucrose density gradient centrifugation of
      isolated membranes, the detergents Triton X-100 and sodium lauryl sarcosinate and
      immunoblotting with a specific FaeD antiserum. Cells containing the complete K88
      operon, as well as cells containing the subcloned faeD gene in various expression
      vectors, were used. Most of the FaeD was present in the outer membranes in a
      detergent-resistant form. Agglutination experiments with E. coli cells expressing
      FaeD confirmed an outer membrane localization and indicated the presence of FaeD
      at the cell surface. Automated Edman degradation indicated that the mature FaeD
      contained 777 amino acid residues and confirmed that FaeD is synthesized with a
      rather long signal sequence of 35 amino acid residues. Twelve different FaeD-PhoA
      fusion proteins were prepared and characterized by nucleotide sequencing and
      immunoblotting. Most of these fusion sites were located in the amino-terminal and
      carboxyl-terminal regions of FaeD. Six amino-terminal fusion proteins were
      soluble proteins in the periplasm, whereas the other fusion proteins were
      associated with the outer membrane. The protease accessibility of FaeD and of the
      six outer membrane-bound FaeD-PhoA fusion proteins was studied using whole cells,
      cells with permeabilized outer membranes, and isolated membranes. Collagenase H,
      kallikrein, trypsin and proteinase K were used. Based on the results of these
      experiments and computer predictions, a model for the membrane topology of FaeD
      was developed in which FaeD contains a large central domain containing 24
      membrane-spanning segments and two relatively large periplasmic regions, at the
      amino-terminal and carboxyl-terminal end of the protein, respectively.

PMID- 8577258
TI  - Identification of GroEL as a constituent of an mRNA-protection complex in
      Escherichia coli.
AB  - An RNA-binding activity has been identified in Escherichia coli that provides
      physical protection of RNA against ribonucleases in an ATP- and Mg(2+)-dependent
      manner. This binding activity is stimulated under growth conditions known to
      cause a decrease in the rate of mRNA decay. RNA protection is mediated by a
      protein complex that contains a modified form of the chaperonin GroEL as an
      indispensable constituent. These results suggest a new role for GroEL as an RNA
      chaperone.

PMID- 8577259
TI  - Proposal for a peptidoglycan-associating alpha-helical motif in the C-terminal
      regions of some bacterial cell-surface proteins.

PMID- 8577260
TI  - Mycobacterium paratuberculosis and inflammatory bowel disease: frequency
      distribution in serial colonoscopic biopsies using the polymerase chain reaction.
AB  - An association between Mycobacterium paratuberculosis and Crohn's disease is
      suspected but the evidence remains controversial. Using a one-step DNA extraction
      procedure with the thermophilic protease PRETAQ and amplification by the
      polymerase chain reaction, M. paratuberculosis DNA was detected in 22% of
      patients with Crohn's disease, and in 13% of patients with ulcerative colitis. M.
      paratuberculosis DNA was not found in any biopsy tissue from control non
      inflammatory bowel disease patients. The biopsy tissues in which M.
      paratuberculosis was detected all came from regions which were inflamed when
      viewed microscopically. Overall, 7.7% of biopsies from such inflamed areas were
      positive. This low frequency of detection could be explained on the basis of
      extremely low abundance of the organism in relation to the area of mucosa
      sampled, or be consistent with a non-aetiological role for M. paratuberculosis in
      inflammatory bowel disease.

PMID- 8577261
TI  - Isolation and partial characterization of yeast mannan hydrolysing enzymes from
      bacterial isolates.
AB  - A range of aerobic, mesophilic bacterial strains capable of producing
      extracellular alpha-mannanase and alpha-mannosidase enzymes were isolated from
      various natural habitats using yeast cell wall material as the selective medium.
      Five of them were capable of producing extracellular alpha-mannosidase and alpha
      mannanase on yeast mannan as the sole carbon substrate, and they were tentatively
      identified to the genus level as Arthrobacter, Streptomyces, Pseudomonas,
      Bacillus and Acinetobacter. Among these strains, Arthrobacter M-02 showed the
      highest biosynthetic activity of the enzymes. The crude enzyme preparations from
      the strains were active at pH 4 to 9, reaching a maximum activity between 5.5 and
      6.8. The crude Arthrobacter M-02 alpha-mannosidase was more thermostable than
      that of the other strains, but the alpha-mannanase of the strain was
      thermolabile.

PMID- 8577262
TI  - Reduced uptake of nickel by a nickel resistant strain of Candida utilis.
AB  - A nickel resistant strain of the yeast Candida utilis was obtained by selection
      of spontaneous mutants on solid medium containing 3 mM Ni2+. In time-course
      experiments, non-growing suspensions of the mutant strain took up approximately
      50% less nickel than the parent strain over 30 min incubation in MES buffer plus
      glucose at pH 5.5. Efflux of nickel from either strain was negligible. Uptake was
      reduced by omission of glucose from the uptake buffer in both strains but this
      was much more marked in the parent strain. Uptake of nickel in the presence of
      equimolar concentration of Mg2+ was reduced by 80% in both parent and mutant
      strains. It was concluded that resistance to nickel was due to an alteration in a
      transport system primarily responsible for uptake of magnesium.

PMID- 8577263
TI  - The measurement of swimming velocity of Vibrio cholerae and Pseudomonas
      aeruginosa using the video tracking methods.
AB  - The swimming velocities of two monotrichous flagellated bacteria were measured by
      a computer-assisted video tracking method. Tracing the moving path of the
      individual bacterium revealed that the bacterial cell did not swim continuously
      in a straight direction, but frequently changed swimming direction and velocity.
      The average swimming velocities calculated from the 3-sec path were 75.4 +/- 9.4
      microns/sec in four strains of Vibrio cholerae and 51.3 +/- 8.4 microns/sec in
      five strains of Pseudomonas aeruginosa. These results suggest that V. cholerae
      swim faster than P. aeruginosa at 30 C in nutrient broth. This method is useful
      for a detailed analysis of bacterial movement and moving patterns in different
      environmental conditions.

PMID- 8577264
TI  - Construction of a combined NotI/SmaI physical and genetic map of Moraxella
      (Branhamella) catarrhalis strain ATCC25238.
AB  - Using pulsed field gel electrophoresis (PFGE) and Southern hybridization
      techniques, a physical map of Moraxella catarrhalis strain ATCC25238 was
      constructed to provide basic genetic knowledge of this bacterium that has
      attracted attention in recent years as a human pathogen. Restriction endonuclease
      NotI cut the genome into 10 fragments and SmaI into 9, and the molecular size of
      the genome was estimated to be 1,940 kilobases. Location of the 12 genes
      participating in the biosynthesis of purine, pyrimidine and nine kinds of amino
      acids were determined on the circular physical map of the strain.

PMID- 8577266
TI  - Demonstration of a ferric vibrioferrin-binding protein in the outer membrane of
      Vibrio parahaemolyticus.
AB  - Under iron-restricted conditions, Vibrio parahaemolyticus produces a siderophore,
      vibrioferrin, accompanying expression of two major outer membrane proteins of 78
      and 83 kDa. Autoradiographic analysis of nondenaturing polyacrylamide gel
      electrophoregrams of outer membrane preparations previously incubated with
      [35Fe]ferric vibrioferrin revealed a single radiolabeled band, in which the 78
      kDa protein was detected predominantly by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis. The antiserum against the purified 78-kDa protein partially
      inhibited Fe-VF binding to isolated OMPs. The 78-kDa protein was cleaved by the
      treatment of whole cells with proteinase K, indicating that a portion of this
      protein is exposed on the surface of the outer membrane. The treated cells lost
      most of their iron uptake activity mediated by vibrioferrin. These results
      suggest that the ferric vibrioferrin-binding protein of 78 kDa may function as
      the receptor for ferric vibrioferrin involved in the initial step of vibrioferrin
      mediated iron uptake. Immunoblot analysis using the antiserum against the 78-kDa
      protein demonstrated that the molecular mass and antigenic properties of the
      protein were highly conserved among V. parahaemolyticus strains examined. The
      antiserum also recognized an iron-repressible outer membrane protein of 78 kDa
      from iron-restricted V. alginolyticus strains, some of which appeared to produce
      vibrioferrin.

PMID- 8577265
TI  - Growth conditions influence expression of cell surface hydrophobicity of
      staphylococci and other wound infection pathogens.
AB  - The initial adhesion of microbes to tissue and solid surfaces can be mediated by
      hydrophobic interaction. Expression of microbial cell surface hydrophobicity
      (CSH) is influenced by growth conditions, and often best expressed after growth
      under nutrient-poor conditions, or "starvation". In the present study, the CSH of
      133 strains of Enterobacteriaceae, Staphylococcus aureus, coagulase-negative
      staphylococci, Enterococcus faecalis, group A streptococcus, Pseudomonas
      aeruginosa, Clostridium perfringens, Bacteroides fragilis, Peptococcus magnus,
      and of 8 Candida albicans strains was measured by the salt aggregation test after
      growth on hematin agar in a 5% CO2 atmosphere, or under anaerobiosis. Cells of
      all but 8 strains expressed pronounced or moderate CSH, i.e., they aggregated in
      0.01-2 M ammonium sulfate. When the agar surface was covered by human serum
      (diluted 1:5) to mimic growth conditions in a wound, 94 strains expressed higher
      CSH, and 44 strains the same CSH as after growth without serum. The CSH of 12
      strains of different species was measured after growth on blood, hematin and PDM
      agar, with or without serum, and in an aerobic or a 5% CO2 atmosphere. The
      highest CSH was expressed after growth in 5% CO2 with serum, and the lowest
      growth after on blood agar in aerobic atmosphere. Identical results were obtained
      with native and heat-inactivated (56 C, 20 min) serum. The reduced surface
      tension obtained in 5% CO2, as well as yet unidentified serum factors, promotes
      expression of CSH.

PMID- 8577267
TI  - Immunological characterization of the neurotoxin produced by Clostridium
      botulinum type A associated with infant botulism in Japan.
AB  - The neurotoxin associated with type A infant botulism in Japan shows different
      antigenic properties from those produced by authentic strains. The monoclonal
      antibodies recognizing the light chain reacted to both neurotoxins, whereas half
      the antibodies recognizing the heavy chain reacted specifically to the respective
      neurotoxin. Each neurotoxin showed its own manner of binding to brain
      synaptosomes. These results indicate that the distinguishable characteristics are
      ascribable to the heavy chain but not to the light chain. In both neurotoxins, an
      epitope recognized by the monoclonal antibody that reacts to the light chain and
      neutralizes the toxin was found to be very close to the amino-terminal half (H-1
      fragment) of the heavy chain. This may support the hypothesis that the H-1
      fragment functions in the transport of the light chain in the target cell.

PMID- 8577269
TI  - Analysis of the relationship between cellular thymidine kinase activity and
      virulence of thymidine kinase-negative herpes simplex virus types 1 and 2.
AB  - The virulence of thymidine kinase-negative herpes simplex virus type 1 (HSV-1;
      VRTK- strain) and type 2 (HSV-2; UWTK- strain) was studied in comparison with
      that of their parental strains (VR-3 and UW-268, respectively) in an encephalitis
      model of adult (4-week-old) and newborn (3-day-old) mice. Viral thymidine kinase
      (TK) activity was essential for the maximum expression of virulence of HSV-1,
      because the 50% lethal dose (LD50) of VRTK- was 60 times higher than that of VR-3
      in the brains of newborn mice expressing high levels of cellular TK activity.
      However, the UWTK- strain showed that replication of the UWTK- strain was
      completely supported by cellular TK activity. This difference in the role of
      viral and cellular TKs for virus growth between HSV-1 and HSV-2 was? confirmed
      with the one-step growth of virus strains in L-M and L-M(TK-) cells.

PMID- 8577268
TI  - Three antigenic regions in p17 of human immunodeficiency virus type 1 (HIV-1)
      revealed by mouse monoclonal antibodies and human antibodies in HIV-1 carrier
      sera.
AB  - We investigated the murine antibody response to recombinant p17 (rp17) of human
      immunodeficiency virus type 1 (HIV-1) and the human antibody response directed to
      p17 in HIV-1 infection. Three large peptides covering residues 12-29, 53-87 and
      87-115 of p17 were synthesized. The cysteine residues 57 and 87 of peptide 53-87
      were reoxidized to form a disulfide bridge. Eighteen out of 19 murine monoclonal
      anti-rp17 antibodies had relatively high affinities (KA = 1.9 x 10(5)-1.4 x 10(8)
      M-1) with one of the 3 p17 peptides in the liquid phase. Each monoclonal antibody
      reacted only with one particular peptide and had no reactivity with the other 2
      p17 peptides. All the monoclonal antibodies reacted with rp17 in the liquid phase
      with a reasonable degree of affinity (KA = 2.0 x 10(5)-1.8 x 10(7) M-1). Four HIV
      1 carrier sera, which were positive in ELISA using rp17 as the antigen, reacted
      positively in an ELISA using 3 p17 peptides which were used to titrate murine
      monoclonal antibodies. Murine monoclonal antibodies having specificity for the 3
      p17 peptides stained live HIV-1-infected cells by means of indirect membrane
      immunofluorescence, irrespective of their specificity. This suggests that the
      various portions of p17 (at least 3 regions of p17) were exposed on the surface
      of live infected cells, probably as short polypeptide chains.

PMID- 8577270
TI  - Class-specific antibody response in acyclovir-treated and adenine arabinoside
      treated patients with primary genital herpes simplex virus infection.
AB  - Herpes simplex virus (HSV) class-specific antibody responses after primary
      genital herpes infection were evaluated with an enzyme-linked immunosorbent assay
      (ELISA) in 16 patients treated with acyclovir (ACV), given orally, and 17
      patients treated with adenine arabinoside (Ara-A), given topically. ACV
      significantly suppressed the levels of IgM, IgA, and IgG. In the ACV-treated
      patients, IgM and IgG were not detected in 4 of the 16 and in 1 of the 16
      patients, respectively. We must take into account this suppressive effect of ACV
      on antibody responses, especially on the IgM response, when serodiagnosis of HSV
      infection is made.

PMID- 8577271
TI  - A 38-kDa antigen of Mycobacterium tuberculosis predominantly induces the
      secretion of interleukin-2, interferon-gamma and IgG2a antibodies.
AB  - In the present study, mice of 3 different haplotypes (H-2d, H-2k and H-2b) were
      sensitized subcutaneously with heat-killed H37Ra or 38-kDa antigen of
      Mycobacterium tuberculosis. Lymphocytes obtained from immunized animals were
      challenged in vitro with 38-kDa antigen in both cases. The dominant pattern of
      Th1-like lymphokines (IL-2 and IFN-gamma) and preferential production of 38-kDa
      specific IgG2a-type antibody were observed. It was noted that 38-kDa antigen was
      recognized permissively by all 3 strains of mice used in the present study. It
      was interesting to note that C3H/HeJ mice, which express BCG-resistant alleles
      showed a higher level of proliferative as well as cytokine response as compared
      to BALB/c and C57BL/6 mice, which bear BCG-susceptible alleles. These results
      suggest that not only in recall responses but also during the induction as well
      as expression phase of the immune response mediated by 38-kDa antigen of M.
      tuberculosis the Th1-like immune response predominates.

PMID- 8577272
TI  - Differential effects of prostaglandin E1 and prostaglandin E2 on growth and
      differentiation of murine myeloid leukemic cell line, M1.
AB  - Effects of prostaglandins (PGs) of the E series on growth and differentiation of
      murine myeloid leukemic cell line M1 were studied. PGE1, but not PGE2, inhibited
      the growth of M1 cells. PGE2 neither inhibited nor augmented the
      antiproliferative effect of PGE1. PGE1 augmented the differentiation of M1 cells
      into macrophage-like cells induced by interleukin 6. PGE2, however, did not
      exhibit any effect on the differentiation. PGE1 caused a marked increased in
      intracellular cAMP level in M1 cells, whereas PGE2 had no effect. These results
      indicate that M1 cells are able to respond only to PGE1. Radiolabeled PGE1
      binding experiments, however, revealed that there was no specific binding in M1
      cells, suggesting that the cells express low numbers of receptors or very low
      affinity receptors specific for PGE1. Stable agonists of PGI2, iloprost,
      cicaprost or carbacyclin, also potently inhibited the growth of M1 cells. These
      findings suggest that PGE1 as well as PGI2 may play a role in the differentiation
      of monocyte-macrophage lineage cells.

PMID- 8577273
TI  - Monomer of the B subunit of heat-labile enterotoxin from enterotoxigenic
      Escherichia coli has little ability to bind to GM1 ganglioside compared to its
      coligenoid.
AB  - Coligenoid, composed of the B subunit of heat-labile enterotoxin from
      enterotoxigenic Escherichia coli, was separated into monomers in the presence of
      2% propionic acid containing 6 M urea (pH 3.8). Monomers equilibrated against
      0.75% or 0.5% propionic acid containing 3 M urea (pH 3.8) did not reassemble into
      coligenoid. Complexes of GM1 ganglioside and coligenoid in these buffers were
      detected by SDS-polyacrylamide gel electrophoresis, but those of the GM1
      ganglioside and monomers were not. The binding ability of monomer to GM1
      ganglioside in these buffers was about 1% of that of normal coligenoid by GM1
      enzyme-linked immunosorbent assay. Moreover, monomers in these buffers
      reassembled into coligenoid by buffering against original TEAN buffer, and the
      binding ability of the resulting coligenoid to GM1 ganglioside was identical to
      that of native coligenoid. These data suggest that although coligenoid formation
      is important for the receptor binding of the B subunit, little binding ability to
      GM1 ganglioside remains in monomer of the B subunit.

PMID- 8577274
TI  - Yersinia pseudotuberculosis in China.
AB  - Thirty strains of Yersinia pseudotuberculosis were isolated from rabbits (17
      strains), wild rats (9 strains) and house rats (4 strains) in China between 1990
      and 1993. The biochemical properties of these isolates were identical with those
      of Y. pseudotuberculosis and no special characteristics were found in these
      strains. Serologically, serogroups 4b and 5b were identical to isolates found in
      Japan, and a new serogroup 1c and unclassified strains have also been detected.
      The existence of virulence-associated properties were different among strains.
      The pYV plasmid was detected from 6 strains of 30 isolates. This report documents
      the presence of Y. pseudotuberculosis in China, providing important
      epidemiological information.

PMID- 8577275
TI  - Detection of astroviruses from stool samples in Japan using reverse transcription
      and polymerase chain reaction amplification.
AB  - We developed a reverse transcription and polymerase chain reaction (RT-PCR)
      method for detecting astrovirus serotypes 1, 2, 3, 5, 6 and 7 (but not serotype
      4). Furthermore, we developed the specific primers for detecting serotypes 1 and
      2, the most predominant serotypes in the world. Sensitivity of the first PCR with
      serotype common primers was about 10 times higher than that of enzyme immunoassay
      with monoclonal antibody (EIA-MAb). Sensitivity of the second PCR with the
      serotype-specific primers was even higher. The RT-PCR method was useful for
      detecting astroviruses from clinical samples, especially serotypes 1 and 2.

PMID- 8577276
TI  - The purification of a GroEL-like stress protein from aerobically adapted
      Campylobacter jejuni.
AB  - From plate cultures of Campylobacter jejuni grown in room air a particulate
      protein of 62 kDa was isolated by ion-exchange chromatography. The protein had a
      square shape from the side view but when viewed from the top it had a star-shaped
      structure. The molecular size of the whole particle determined by gel filtration
      was 850 kDa which suggested the presence of 14 subunits of 62 kDa in each
      particle. The N-terminal 37 amino residues showed more than 80% homology with the
      sequence of these heat shock protein (HSP) 60 homologs of Chlamydia trachomatis,
      Helicobacter pylori, and Escherichia coli (GroEL). This protein is
      immunologically cross-reactive with the antiserum for the 60-kDa HSP of Yersinia
      enterocolitica. Production of the 62-kDa protein increased under heat stress and
      growth in an aerobic atmospheric environment. From these observations we
      concluded that the 62-kDa protein is a Campylobacter stress protein (Cj62) which
      belongs to the HSP 60 family.

PMID- 8577277
TI  - Temperature effects on Legionella pneumophila killing by and multiplication in
      phagocytes of guinea pigs.
AB  - We examined the effects of temperature on the interaction between Legionella
      pneumophila and phagocytes of guinea pigs. The body temperatures of guinea pigs
      infected with a sublethal dose (1.2 x 10(4) CFU) or a lethal dose (1.0 x 10(5)
      CFU) of L. pneumophila elevated from 38.4 +/- 0.15 C to 40.2 +/- 0.42 C or 40.3
      +/- 0.62 C, respectively. The intracellular bacterial killing by and bacterial
      proliferation in the phagocytes were examined at 33, 37, 40, and 42 C, using in
      vitro culture systems of peritoneal macrophages or polymorphonuclear leukocytes
      (PMN) of guinea pigs. In all the macrophages incubated at different temperatures,
      significant intracellular bacterial killings were observed at 4 hr after in vitro
      phagocytosis. After 24 hr of incubation, there was about a 100-fold increase of
      CFU and the number reached a maximum after 48 hr of incubation in the macrophages
      incubated at 42 C as well as 37 and 40 C, suggesting that macrophages support the
      intracellular bacterial growth in hyperthermia. In the PMN, L. pneumophila CFU 4
      hr or 12 hr after the infection were significantly lower at 42 C than those at 37
      C (P < 0.05), indicating that the bactericidal capacity of PMN was enhanced at 42
      C compared to 37 C. However, in all the PMN incubated at different temperatures,
      there were about 10-fold increases of CFU 24 hr after the infection, suggesting
      that PMN as well as macrophages support intracellular bacterial growth in
      hyperthermia. The extracellular bacterial growth was examined at 33, 37, 40, and
      42 C in buffered yeast extract (BYE) broth or RPMI 1640 medium containing 50%
      guinea pig serum as a permissive or non-permissive liquid medium for the
      bacterial growth, respectively. Inhibition of bacterial growth in BYE broth at 42
      C, and a decrease of CFU in RPMI 1640 medium containing 50% guinea pig serum at
      42 C were observed. In conclusion, hyperthermia may be beneficial by restricting
      extracellular bacterial survival, but it exerts no beneficial effect on the
      restriction of intracellular bacterial growth in phagocytes, though PMN showed
      enhanced initial killing at 42 C. These results suggest that fever, or
      hyperthermia itself, may not largely contribute as a nonspecific host defense
      early in the course of legionellosis.

PMID- 8577278
TI  - Isolation, and virulence profiles, of Aeromonas hydrophila implicated in an
      outbreak of food poisoning in Sweden.
AB  - A case of food poisoning outbreak involving Aeromonas hydrophila is reported in
      this study. A group of 27 people consumed a typical Swedish food "landgang" which
      is a type of smorgasbord containing shrimps with mayonnaise, liver pate, ham,
      sausage, and legume salad which was purchased from a food store. Twenty-two of
      the 27 persons became ill within 20-34 hr of consumption of the food and reported
      the symptoms ranging from severe acute diarrhea, abdominal pain, headache, fever
      and vomiting. One person also fainted. The symptoms lasted for a couple of days.
      Of the remaining 5 healthy persons who consumed the left-over food the next day,
      2 became ill with similar symptoms. The bacteriological examination of left-over
      food samples resulted in the isolation of A. hydrophila from shrimps with
      mayonnaise, smoked sausage, liver pate and boiled ham. The total number of A.
      hydrophila in these foods were log 10(6) to log > 10(7) organisms per gram of
      food sample. A. hydrophila was however, not isolated from legume/mayonnaise salad
      samples. All the food samples tested showed low numbers of other expected food
      contaminating organisms such as coliforms at 37 C and 44 C, fecal streptococci,
      Staphylococcus aureus, fungi and yeast etc., while Bacillus cereus, Clostridium
      perfringens and Salmonella spp. were not detected in the food samples.
      Investigations of the virulence profiles of the A. hydrophila isolates showed
      their capacity to produce beta-hemolysin, cytotoxins, cytotonic toxins,
      enterotoxins, and adhesion to and invasion of human intestinal (Henle 407) cells
      in culture.

PMID- 8577279
TI  - Isolation of Coxiella burnetii from dairy cattle and ticks, and some
      characteristics of the isolates in Japan.
AB  - Coxiella burnetii was isolated from raw milk (36/214, 16.8%) and uterus swab
      samples (13/61, 21.3%) originating from dairy cattle with reproductive disorders,
      aborted bovine fetus samples (2/4, 50%), mammary gland samples (4/50, 8%)
      originating from healthy dairy cattle, and tick samples (4/15, 26.7%) originating
      from 2 pastures. Fifty-nine strains had various degrees of pathogenicity, high
      (8; 13.6%), moderate (28; 47.5%) and low (23; 39%), for guinea pigs. The results
      of isolation suggested a high prevalence of Coxiella infection in dairy cattle
      with reproductive problems in Japan. Twelve strains (7, 2 and 3 strains from
      cattle, ticks and humans, respectively) and the reference Nine Mile strain of
      phases I and II were propagated in both yolk sacs of embryonated hen eggs and
      Buffalo green monkey (BGM) cell cultures. Protein profiles of these strains were
      similar to those of the reference strain of phase I. Lipopolysaccharide (LPS)
      profiles of 12 strains were similar to those of the reference strain of phase I
      and different from those of the reference strain of phase II. The LPS profiles of
      12 strains suggested that these strains are associated with an acute form of Q
      fever.

PMID- 8577280
TI  - Evaluation of DNA fingerprinting by PFGE as an epidemiologic tool for Salmonella
      infections.
AB  - To evaluate DNA fingerprinting as an epidemiologic tool, pulsed-field gel
      electrophoresis (PFGE) was performed on isolates of Salmonella, including S.
      typhimurium, S. thompson, and S. enteritidis. Chromosomal DNA was digested with
      the restriction endonucleases Bln I and Xba I. The patterns of S. thompson and S.
      typhimurium isolates from various sources were different from one another. There
      was no correlation between the phage type and the digestion pattern of S.
      enteritidis isolates. Some strains belonging to one phage type were distinguished
      by their PFGE pattern in this study. These results suggest that the Bln I and Xba
      I digestion patterns of chromosomal DNA are useful for epidemiological analysis
      of an outbreak of Salmonella infection or food poisoning.

PMID- 8577281
TI  - Sequence analysis of flanking regions of the pfoA gene of Clostridium
      perfringens: beta-galactosidase gene (pbg) is located in the 3'-flanking region.
AB  - The 3'-flanking region of the perfringolysin O (theta-toxin) gene (pfoA) of
      Clostridium perfringens was analyzed by chromosome walking. A total of 5,363 bp
      of the downstream region of the pfoA gene was sequenced and four open reading
      frames were found. ORF54 and ORF80 were found to be homologous to genes coding
      for membrane-bound transporter proteins of other bacteria and the beta
      galactosidase gene (bgaB) of Bacillus stearothermophilus, respectively. ORF80 was
      named the pbg gene. Clones which showed beta-galactosidase activities were
      selected from a lambda FIXII genomic library of C. perfringens by blue plaque
      screening using X-Gal as a substrate. Four clones whose plaques showed blue
      appearances were obtained. Two of the four clones hybridized with the pbg probe
      but the others did not, indicating that there are two distinct beta-galactosidase
      genes in C. perfringens. The pbg gene was subcloned into pBR322 and was
      successfully expressed in Escherichia coli, suggesting that the pbg gene codes
      for a beta-galactosidase of C. perfringens.

PMID- 8577282
TI  - Identification of the sites for suppressor mutations on the hemagglutinin
      molecule to temperature-sensitive phenotype of the influenza virus.
AB  - A temperature-sensitive (ts) mutant of the influenza virus A/WSN/33 strain, ts
      134, possessed a defect in intracellular transport at the nonpermissive
      temperature and marked thermolability of hemagglutinin (HA) activity at 51 C.
      These were caused by a change at amino acid residue 157 from tyrosine to
      histidine in the HA protein. We isolated 37 spontaneous revertant clones from ts
      134 at the nonpermissive temperature and determined their HA sequences. The
      deduced amino acid sequences demonstrated that one was a true revertant and the
      others were revertants with suppressor mutations, each of which had an additional
      amino acid change besides those of ts-134. The changed amino acids were located
      at 14 positions on the HA molecule, and eight of them were found in multiple
      revertants. These were located in five to six distinct regions on the three
      dimensional structure of the HA molecule. However, the heat stability of HAs in
      the revertants was recovered differently depending on the sites of the changed
      amino acids. The kinetics of transport of the HA protein in the revertants were
      slightly delayed compared to the wild-type both at permissive and nonpermissive
      temperatures.

PMID- 8577283
TI  - Mapping and characterization of a sequential epitope on the rabies virus
      glycoprotein which is recognized by a neutralizing monoclonal antibody, RG719.
AB  - We have established a murine hybridoma cell line RG719 which produces a rabies
      virus-neutralizing IgM-type monoclonal antibody (referred to as MAb RG719).
      Immunoblot analysis indicated that the antibody recognized a sequential epitope
      of G protein. Among four rabies virus strains tested, the antigenicity to MAb
      RG719 was absent from the Nishigahara strain, while the other three strains (HEP,
      ERA and CVS) reacted to the MAb. Studies with deletion mutants of the G protein
      indicated that the epitope was located in a middle region of the primary
      structure of G protein, ranging from position 242 to 300. By comparing the
      estimated amino acid sequence of the four strains, we found in this region two
      amino acids (at positions 263 and 291) which are common to three of those strains
      but are not shared by the Nishigahara strain. The site-directed point mutagenesis
      revealed that replacement of phenylalanine-263 by leucine destroyed the epitope
      of the HEP G protein, while the epitope was generated on the Nishigahara G
      protein whose leucine-263 was replaced by phenylalanine. These observations
      suggest that phenylalanine-263 is essential for constructing the epitope for MAb
      RG719. The synthetic 20-mer peptide produced by mimicking the amino acid sequence
      (ranging from amino acid positions 249 to 268) of the presumed epitope region was
      shown to bind specifically to MAb RG719 and also to raise the virus-neutralizing
      antibodies in rabbits. Vaccination with the HEP vaccine produced in Japan induced
      in humans and rabbits production of significant amounts of the antibodies which
      reacted with the 20-mer peptide.

PMID- 8577284
TI  - Enhanced expression of Fc receptors on neutrophils from calves with leukocyte
      adhesion deficiency.
AB  - The expression of Fc receptors for immunoglobulin G(IgG) and concanavalin A (con
      A)-binding receptors, luminol-dependent chemiluminescent (LDCL) responses, and
      the effect of anti-bovine IgG on LDCL responses were evaluated in neutrophils
      from Holstein calves with leukocyte adhesion deficiency (BLAD). Neutrophils from
      affected calves showed a 2.1- to 2.5-fold increase in Fc receptor expression
      compared with those of control calves by flow cytometric analysis. Con A-binding
      activities of neutrophils from affected calves were similar to those of control
      calves. Neutrophils from a calf with BLAD, when stimulated with zymosan opsonized
      with bovine serum (OPZ), heat-aggregated bovine IgG (Agg-bovine IgG), sheep red
      blood cells (SRBC) sensitized with anti-SRBC antibody (SRBC-anti-SRBC Ab), or con
      A had LDCL responses of 36 (P < 0.05), 77, 126 and 119% of peak LDCL values of
      controls, respectively. The NBT-reducing value of neutrophils from a calf with
      BLAD when stimulated with Agg-bovine IgG after pretreatment with anti-bovine IgG
      was 116.5% of the values of neutrophils from control calves, but the difference
      was not significant. The LDCL responses of neutrophils from a control calf and a
      calf with BLAD stimulated with OPZ were inhibited markedly by pre-incubation with
      anti-bovine IgG antiserum at concentrations ranging from 1.25 to 20 or 40
      micrograms/ml. Although an increase in Fc receptor expression on neutrophils from
      calves with BLAD was observed, the LDCL responses stimulated with SRBC-anti-SRBC
      Ab and NBT-reducing activity stimulated with Agg-bovine IgG after pretreatment
      with anti-bovine IgG did not correlate significantly with the increased Fc
      receptor expression. These results support that neutrophil functions mediated by
      the Fc receptors are associated synergistically with the presence of the
      complement receptor type 3 (CR3)(CD11b/CD18).

PMID- 8577285
TI  - Suppression of cytokine production in T helper type 2 cells by nitric oxide in
      comparison with T helper type 1 cells.
AB  - We examined the effect of nitric oxide (NO) on cytokine production in T helper
      (Th) cell subsets, using murine splenic CD4+ T cells and two types of Th clones.
      Interferon-gamma-treated murine peritoneal exudate cells (IFN-PEC) suppressed DNA
      synthesis to 60% of the control level in CD4+ T cells stimulated with the anti
      CD3 monoclonal antibody. The production of IL-2 and IL-4 in the CD4+ T cells
      decreased to 63.2% and 9.2%, respectively, of the control value by co-culture
      with IFN-PEC. The addition of NG-monomethyl-L-arginine (L-NMMA) partially
      recovered the suppression of DNA synthesis. In the presence of indomethacin, the
      suppression of DNA synthesis was partially inhibited and the reduction in the
      cytokine production caused by IFN-PEC was partially recovered. The simultaneous
      addition of NG-monomethyl-L-arginine (L-NMMA) and indomethacin completely
      inhibited not only the suppression of DNA synthesis but also the reduction in the
      cytokine production caused by IFN-PEC. Moreover, DNA synthesis in the Th2 clone
      was suppressed to a greater extent than that in the Th1 clone by co-culture with
      IFN-PEC. This suppression in the Th1 clone was inhibited by the addition of L
      NMMA, whereas the DNA synthesis in the Th2 clone was not recovered by L-NMMA. In
      addition, sodium nitroprusside (SNP) suppressed IL-4 production in the Th2 clone
      but had no effect on IL-2 production in the Th1 clone. In the experiment of the
      co-culture with IFN-PEC, the inhibitory-effect of NO on T cell activation was not
      clarified by the influence of prostaglandins. However, in conclusion, cytokine
      production in Th2 cells may be more susceptible to NO than that in Th1 cells.

PMID- 8577286
TI  - Inhibition by bacterial lipopolysaccharide of spontaneous and TNF-alpha-induced
      human neutrophil apoptosis in vitro.
AB  - In the previous paper (Takeda et al, Int. Immunol., 5, 691-694, 1993), we
      demonstrated that tumor necrosis factor-alpha (TNF-alpha) promptly accelerates
      apoptosis of human neutrophils in vitro. In order to determine the role of
      neutrophil apoptosis in defending against bacterial infection, we studied the
      effect of bacterial lipopolysaccharide (LPS) on this process. LPS inhibited
      spontaneous and TNF-alpha-induced human neutrophil apoptosis in vitro, as
      determined by 1) light and electron microscopy, 2) flow cytometry, and 3) agarose
      gel electrophoresis of DNA. Low concentrations of cycloheximide, a protein
      synthesis inhibitor, which alone did not affect neutrophil apoptosis, were able
      to reduce spontaneous apoptosis inhibition by LPS, suggesting the involvement of
      newly synthesized protein in this phenomenon.

PMID- 8577287
TI  - Subcutaneous growth of Staphylococcus aureus concomitantly inoculated with
      Ehrlich ascites tumor cells.
AB  - Intratumoral growth of Staphylococcus aureus Cowan I-derived AP332 was examined
      by subcutaneous inoculation of cocci in doses ranging from 18 to 1.8 x 10(5) CFU
      with Ehrlich ascites tumor cells. Inoculation of 18 CFU AP332 resulted in
      staphylococcal growth in one of five mice, and the proportion of mice established
      intratumoral infection increased with the initial inocula. Six other strains of
      S. aureus also grew in the tumor tissue, and none of the three strains of
      coagulase-negative staphylococci grew at all. Ethanol-killed tumor cells did not
      promote staphylococcal growth as vigorously as the live tumor cells, especially
      when the initial inoculum of AP332 was smaller than 10(4) CFU.

PMID- 8577288
TI  - Characterization of Streptococcus sanguis isolated from patients with Behcet's
      disease.
AB  - The DNA homology and cell wall sugar constituents of eight Streptococcus sanguis(
      like) strains, three isolated from the patients with Behcet's disease (BD114-23,
      BD113-20, BD118-1), two from patients with Kawasaki disease (MCLS-1, MCLS-2), and
      three type and reference strains of ATCC (ATCC10556T: S. sanguis, ATCC10557: S.
      oralis, and ATCC10558T: S. gordonii) were analyzed. Strains BD114-23 and BD118-1
      showed high DNA homology to ATCC10556T, and their cell wall constituents were
      identical. Conversely, BD113-20, MCLS-1, MCLS-2, and ATCC10557 showed little DNA
      homology to ATCC10556T and ATCC10558T, but showed approximately 50 to 60%
      homology to each other. The cell wall constituents of BD113-20, MCLS-1, MCLS-2,
      and ATCC10557, however, were somewhat different, indicating that some of the
      clinical isolates have different characters from those of the three ATCC strains.

PMID- 8577289
TI  - Prevalence of antibody to hepatitis E virus among healthy individuals in southern
      Taiwan.
AB  - The seroprevalence of hepatitis E virus (HEV) among 997 healthy individuals aged
      6 to 84 years, collected between July 1993 and June 1994 at Kaohsiung-Pingtung
      area in Southern Taiwan was studied. Of the study populations of vegetable
      farmers, elementary school children, volunteer blood donors and college students,
      the prevalence of IgG anti-HEV ranged from 6.4% to 8.8%. In suburban elemantary
      school children of Mang-Chou Village at Pingtung-Hsien, the seroprevalence rate
      (9.6%) was significantly higher than the positive rate (1.5%) found in rural
      aboriginal elementary school of San-Min Village at Kaohsiung-Hsien. IgG anti-HEV
      antibodies were widely distributed among all age groups, with a significantly
      higher percentage (13.1%) in the age group of 46-55 years old.

PMID- 8577290
TI  - Identification of influenza C virus phosphoproteins.
AB  - The HMV-II cells infected with influenza C virus were labeled with inorganic
      [32P]phosphate to identify phosphorylated proteins. Analysis by
      radioimmunoprecipitation with antiviral serum or monoclonal antibodies revealed
      that three major structural proteins of the virus, hemagglutinin-esterase (HE),
      nucleoprotein (NP), and matrix protein (M1) are all phosphorylated in both
      infected cells and virions. It was also observed that, in the presence of trypsin
      (10 micrograms/ml), the unphosphorylated form of the HE glycoprotein was cleaved
      efficiently whereas the phosphorylated form was not, raising the possibility that
      phosphorylation of HE may influence its susceptibility to degradation by
      proteolytic enzymes.

PMID- 8577292
TI  - Profactor-H (elevated circulating insulin): the link to health risk factors and
      diseases of civilization.
AB  - We propose the term Profactor-H for chronic elevated circulating insulin.
      Profactor-H is common in atherosclerosis, essential hypertension, non-insulin
      dependent diabetes mellitus, some forms of obesity, some forms of cancer,
      cardiovascular disease, peripheral vascular disease and some forms of stroke.
      Profactor-H appears to be the central pathophysiologic consideration in the
      etiology of many diseases and health risk factors. Profactor-H's impact depends
      on genetic predisposition, frequency consumption of refined simple and complex
      carbohydrates, deficiency in dietary chromium, sedentary life style and stresses
      of modern day living. In many obese individuals, Profactor-H disturbs metabolic
      balance, favoring anabolic metabolism, and is exacerbated through chronic insulin
      production and impairment of insulin action. This vicious cycle also appears to
      be common in many apparently healthy, non-obese individuals destined to develop
      health risks and diseases in response to long-term adverse consequences of
      Profactor-H. We believe that a four-pronged program which 1) reduces the daily
      frequency of carbohydrate consumption, particularly refined foods and simple
      sugars, 2) supplements the daily dietary intake of chromium, 3) encourages
      activity, and 4) reduces stress, will minimize the impact of Profactor-H and
      thereby reduce health risks and result in improved health.

PMID- 8577291
TI  - Cancer: a biological problem without any natural immunological solution? A
      unified theory, with implications for grafts, pregnancy and tumour
      immunoprophylaxis.
AB  - Stem tumour cells would be paraembryonal cells, major histocompatibility complex
      lacking and able of inducing adjoining cells to become tumour differentiated
      cells with major histocompatibility complex; thus, they would generate a
      histological tumour organization into paraembryonal cell clusters surrounded by
      tumour-differentiated cells. Such an organization, actually found in recent
      studies, might be one factor responsible for the limits of the immunotherapies
      carried out so far. But, there might be another, perhaps more important, factor.
      Analysis of ontogenetic aspects of MHC-nonrestricted immunity would lead, indeed,
      to the prediction that natural killer clones reactive for stem tumour cells
      (paraembryonal cells) would be missing in the adult organism, since they would be
      deleted in particular ontogenetic phases. This might explain why natural killer
      cells locate only in certain organs and nearly not at all in tumour sites. By
      such an analysis, possible evolutive and functional correlations between natural
      killer cells and heat shock proteins, hemopoietic histocompatibility, major
      histocompatibility complex molecules are suggested. From here, explanations and
      implications for grafts, pregnancy and tumour immunoprophylaxis arise.

PMID- 8577293
TI  - Normative medicine.
AB  - Normative medicine is a new approach to health and disease based on Canguilhem's
      philosophy: The normal and the pathological. In the past, disease was nearly
      synonymous with ill health. Advancing technology reveals more and more pre
      clinical aberrations that are not fully fledged diseases, and cannot be regarded
      as ill health. Medicine lacks clear guidelines for dealing with them. While
      competent in specifying how to treat, it generally fails to decide correctly when
      to intervene in the evolving process. This is the main source of medical
      iatrogenesis. Normative medicine is more concerned with health itself and less
      with diseases. It provides criteria when to intervene in the disease process.

PMID- 8577294
TI  - Virally induced arteriosclerosis: increased life expectancy?
AB  - The average human life expectancy has been increasing constantly since first
      observed in Roman Times (particularly during our century). This is usually
      believed to be related to such 'environmental' factors as sanitation and housing
      and to medical intervention. Data obtained from Vital Statistics of the United
      States supported the idea that these explanations are insufficient. Studies on
      persons who had died from conditions associated with advanced stages of
      arteriosclerosis (ischemic heart disease, cerebrospinal disease) showed the
      highest life expectancy. The inflammatory nature of arteriosclerosis and studies
      (by others) indicating 'protective' effects suggested that the developmental
      stages of arteriosclerosis (in contrast to the final stages) promote increased
      life expectancy. Inasmuch as certain viruses (especially the human herpes virus)
      are involved in the development of arteriosclerosis and because nearly everybody
      gets infected during childhood, this virus may be a factor in the increase of
      life expectancy. The work on symbiosis and on hormesis has established the fact
      that small amounts of parasites are often associated with beneficial effects for
      both the host and the parasites. All of this is in line with evolutionary
      expectations.

PMID- 8577295
TI  - The mystery of Alzheimer's disease and its prevention by melatonin.
AB  - Preliminary observation suggested that a melatonin deficiency could cause
      Alzheimer's disease. New evidence reveals that: 1) a significant melatonin
      deficiency is common in the disease, 2) melatonin acts as a hydroxyl radical
      scavenger and 3) brain tissue mitochondria from Alzheimer's patients have damage
      consistent with hydroxyl radical injury.

PMID- 8577296
TI  - Towards a unifying hypothesis of neurodegenerative diseases and a concomitant
      rational strategy for their prophylaxis and therapy.
AB  - Many neurodegenerative diseases have been found to present activated microglia,
      implying that immunologic processes operate which might exacerbate their basic
      pathologies. We consider 14 such disorders which are known or believed to exhibit
      these phenomena. Alzheimer's disease, the principal member of this group, has had
      its progression arrested in clinical trials by an antiinflammatory agent, leading
      us to suggest the possibility of successful prophylactic and therapeutic
      intervention at the immunologic level against these diseases with
      antiinflammatory drugs. It is further suggested that in neurodegenerative
      disorders of unknown etiology or pathogenesis the possible presence of activated
      microglia should be investigated. Finally, the possible relevance of these
      concepts for schizophrenia is examined.

PMID- 8577297
TI  - Mechanochemiemission and atherogenesis.
AB  - Haemodynamic factors activate mechanochemiemission between the surfaces of
      vessels and blood cells, i.e. optical, acoustic, heat and radioemissions which
      initiate formation of lipid peroxide radicals causing vascular wall damage.
      Subsequent development of mechanochemiemission reactions in lipids results in
      formation of atherosclerotic plaques in the arterial intima.

PMID- 8577299
TI  - Cytokines may give insight into mechanisms of death in sudden infant death
      syndrome.
AB  - There are a number of postulated causes of sudden infant death syndrome,
      including bacterial toxins, defects in thermoregulation and hypersensitivity.
      This paper formulates the hypothesis that analysis of cytokine profiles in
      suspected sudden infant death syndrome victims may give an insight into
      mechanisms of death. These cytokine profiles may also help to identify specific
      causes of sudden infant death syndrome or indicate that different causes act in
      concert in individual cases.

PMID- 8577298
TI  - Some characteristics of the glutathione cycle revealed by ionising and non
      ionising electromagnetic radiation.
AB  - The cyclic reaction of GSH-->GSSG-->GSH (designated R(exp) or R(e)) obeys the
      three specific features of life by producing energy in exponential quantities
      relative to time, is in effect irreversible and is inherited from generation to
      generation. In multicellular life, this reaction produces the energy for mitosis
      and is kept in controlled inactivity until needed to maintain perfection of form
      and function by energising mitosis. The immediate control of Re appears to be
      feedback process-dependent on the concentration of GSSG. Ultra high-frequency
      electromagnetic radiation of 434 MHz (UHF) will change Re from inactive to active
      and, in so doing, it causes resonance and/or fluorescence of the glutathione
      cycle which changes its radiosensitivity. Re is the primary direct target of
      ionising radiation and produces the energy for mitosis. Clinical observations
      suggest that, in the normal cell, Re is inactive and is not killed by 3 x 2700
      rads or 6 x 1650 rads yet, when active, its sensitivity value (DO) is
      approximately 160 rads. Using the standard radiobiological equation of response
      to ionising radiation, it can be deduced that radiosensitive cancers have two or
      three Re units active per cell and radioresistance increases in proportion to the
      number of potentially active Re units per cell. Re appears to be the main cause
      of cancers' increased conductivity of electricity compared with normal tissue. In
      cancer therapy, UHF is the best radiosensitiser ever discovered (up to two or
      more decades). Re is also intelligent compared with non-exponential reactions but
      cannot be the basis of intellectual brain functions which must be based on non
      electrical chemical processes.

PMID- 8577300
TI  - A new approach to antiviral therapy.
AB  - A new approach to antiviral therapy is proposed, taking advantage of the recently
      investigated innervation of immune tissues by the sympathetic nervous system,
      which establishes a functional connection between the nervous and the immune
      system, where the sympathetic nervous system exerts a varying tonic inhibitory
      influence on cellular activation via secretion of norepinephrine and reception
      thereof by beta-receptors on leukocytes. Simultaneous beta-adrenergic blockade of
      leukocytes and stress-related centres of the central nervous system
      (paraventricular nucleus of the hypothalamus) is suggested as immunoactivating
      therapy in presence of foreign antigen. Immunoactivation is newly defined as
      facilitated activation of the immune system in presence of foreign antigen and is
      theoretically correlated with indirect antiviral and antitumoral activity.

PMID- 8577301
TI  - Tissue factor initiation of disseminated intravascular coagulation in filovirus
      infection.
AB  - Filovirus infections in humans and primates cause intrinsic activation of the
      clotting cascade. Tissue factor, the normal activator of the clotting cascade, is
      released into the bloodstream from activated leukocytes and viral budding from
      infected cells. This release of tissue factor, a trans-membrane protein found in
      large amounts in cells preferred by filoviruses for replication, initiates the
      hemorrhagic complications characteristic of filovirus infection. These
      complications contribute to the high mortality rates of filovirus infections.
      Directing chemotheraputic measures at the release of tissue factor, which causes
      the hemorrhagic complications, will result in significant reductions of mortality
      rates in man and primates.

PMID- 8577302
TI  - Felonious sex crime: the possibility of unilateral cerebral irradiation for the
      offenders.
AB  - Some felonious sex crimes might result from compulsions that the perpetrator
      finds impossible to control. Under judicial systems derived from British law, the
      court should be extraordinarily careful in mandating any medical procedure.
      However, if a rapist or child molester voluntarily asks a physician for help,
      then medical ethics might allow destruction of part of the patient's brain for
      the purpose of controlling compulsive behaviour. The part of the human brain
      primarily associated with volition might be near the anterior cingulate sulcus.
      Could unilateral irradiation of an area near the anterior cingulate sulcus
      partially destroy the patient's volition? By leaving intact the patient's will
      based on language and by partially destroying the patient's will based on
      intuition, could the physician diminish the patient's will to commit felonious
      sex crimes? Would some patients reject chemical castration but accept unilateral
      irradiation of an area near the anterior cingulate sulcus?

PMID- 8577303
TI  - Observations on the normal distribution of quantitative traits.
AB  - Two experiments are assumed, which show that group equal assortment of genes
      produces a centripetal effect and group unequal assortment of genes produces a
      centrifugal effect. The normal distribution of quantitative traits is
      intermediate between group equal assortment of genes and group unequal assortment
      of genes, which means the reduction division and the assortment of genes are
      relatively equal (not completely equal). From the experiments, we find that
      individual equal assortment of genes produces a centrifugal effect and the
      individual unequal assortment of genes produces a centripetal effect. The
      centrifugal effect of individual equal assortment of genes leads to the result
      that the F2 generation is considerably more variable than the F1 in the Emerson
      East experiment with sweet corn (1). Group assortment interacts with individual
      assortment. The centrifugal effect interacts with the centripetal effect. These
      interactions affect the stability of inheritance and variation.

PMID- 8577304
TI  - Obtaining automated diagnostic information and pain relief.
AB  - The silent confluent flow of a conglomerate of sensory related signals is
      automatically delegated to the total specific distribution of a single spinal
      nerve. This silent confluent flow may be accessed, evaluated, and modified by
      using intradermal saline infiltration to stimulate the sensory receptors located
      in the skin overlying its nerve root. An unmistakable augmented burst of
      infiltration pain immediately followed by profound long lasting pain relief
      identifies a spinal nerve monitoring peripheral pathology. The identification of
      a monitoring spinal nerve tentatively confirms the presence of pathology confined
      to the specific peripheral distribution of that specific spinal nerve. The
      practically unknown visceral distribution proves to be specific and visceral
      pathology echoes through its collated spinal nerve without patent variation.
      Practically cost free and without side effects or contraindications dermatomal
      infiltration opens a whole new chapter in the field of diagnosis as it may be
      used to determine the presence of pathology, to locate that pathology to the
      specific distribution of a specific spinal nerve or nerves, and to produce
      unequalled pain relief.

PMID- 8577305
TI  - Darwin's selection within the human body.
AB  - It has been widely accepted that Darwin's natural selection plays a basic role in
      carcinogenesis and some other disease processes, but is not relevant to the
      normal multicellular life within the human body. The hypothesis proposed here is
      that selection and other evolutionary mechanisms not only normally or
      physiologically exist within the body of human beings and other multicellular
      organisms, but also persist and 'function' throughout the entire life span of the
      organism, from the embryo development to the aging process. This is based on the
      concept of cell individuality and the fact that there are a great deal of
      variations in cell populations, in particular possible existence of somatic
      genetic variations within the body. To realize the existence of natural selection
      in the multicellular life and study how it operates within organisms in both
      physiological and pathological conditions are fundamentally important to our
      understanding of human biology and medicine.

PMID- 8577306
TI  - Sudden infant death syndrome and superoxide/nitric oxide.
AB  - In a sudden infant death syndrome review Valdes-Dapena describes Naeye's report
      of increased medial muscle mass in walls of small pulmonary arteries and
      increased weight of cardiac right ventricles. These findings point to
      cardiorespiratory insufficiency, a problem in fast growing chicks raised at high
      altitudes. The vascular epithelium lining all blood vessels synthesises nitric
      oxide which induces relaxation of smooth muscle in vessel walls, and is possibly
      an important neurotransmitter. Others demonstrate that nitric oxide is involved
      in regulating vessel calibre, blood pressure and blood flow, as well as falls in
      ventricular outputs. Superoxide interacts with nitric oxide and removes it from
      the circulation. Superoxide is thus a vasoconstrictor. Superoxide is produced by
      activated phagocytes and possibly lymphocytes and other cell types in the immune
      response. Elevated immunoglobulins in mucus secretions are a hallmark in sudden
      infant death syndrome and hypoxic chicks. Our approach therefore is that
      cardiorespiratory insufficiency may be induced by superoxide in small pulmonary
      arteries preventing nitric oxide from acting as a muscle relaxant in vascular
      walls.

PMID- 8577307
TI  - Gene regulation and the origin of cancer: a new model.
AB  - The genome is a dynamical system in which regulation is achieved by the algebraic
      logic of Boolean functions. A model of a webbed genetic network is presented. In
      this, all genes lie on interconnected loops, within which each can influence the
      others, forming the basis of a regulatory network. The normal proto-oncogenes and
      tumor suppressor genes serve as gateways or switch points in the genetic
      circuitry, controlling the transition between different cell states. The model
      explains why multiple genes must be perturbed for the formation of a cancer.

PMID- 8577308
TI  - Streaming organism.
AB  - The cell kinetic characteristic of all epithelia is the same. All are analogs of
      the crypt-villus unit of the gastrointestinal mucosa. Each unit is nourished by
      at least one determined uncommitted stem cell (DS). When the DS divides, one of
      its progeny replaces the parent and remains a DS, while the other starts
      streaming outward. When entering a differentiation pathway it is called a
      committed stem cell (CS). Cells in the unit differentiate while streaming.
      Initially they continue multiplying and are called amplifying progenitors (P
      cells), then they lose the capacity to synthesize DNA and become non-dividing
      (quiescent) end cells (Q-cells). All cells except the DS are transitional and
      short lived (in the crypt they live several days): only the DS is permanent.
      Since epithelial tissues are cell kinetic analogs of the crypt, it is assumed
      here that their neoplastic progression is analogous with the adenoma-carcinoma
      sequence of the crypt. Neoplasia starts when a normal cell is transformed into a
      neoplastic. If a transitional cell is hit by a carcinogen and transformed into a
      neoplastic, it soon will be washed out from the system. Only a transformed DS can
      maintain the neoplastic trait since it never leaves the crypt. Neoplasia is thus
      a pathology of the DS. There are two differentiation scales in the embryo: global
      and local. The first starts with the fertilized ovum that divides into stem cells
      that become more and more determined. Following gastrulation each determined stem
      cell generates its local progeny of transitional cells that make the tissue
      units. Determined stem cells are direct descendants of the fertilized ovum, while
      their transitional progenitors are direct descendants of determined stem cells.

PMID- 8577309
TI  - A simple colony-blot method for identification of Listeria in food samples.
AB  - A method for identification of Listeria in food samples was developed. It
      consisted of cultivating of suspected specimen on standard agar medium, direct
      absorption of grown colonies onto nitrocellulose membrane and processing of the
      latter with rabbit serum raised against purified cell wall protein Lm79/39 of L.
      monocytogenes. Analysis using anti-rabbit peroxidase conjugate and 4-chloro-1
      naphthol and H2O2 solutions allowed direct detection of Listeria colonies which
      remained readily available for subsequent isolation.

PMID- 8577310
TI  - Variable degree of slime production is linked to different levels of beta-lactam
      susceptibility in Staphylococcus epidermidis phase variants.
AB  - Recently we demonstrated that lack of mecA transcription was responsible for the
      decreased methicillin resistance phenotype of strongly slime-negative
      Staphylococcus epidermidis phase variants [Mempel M, Feucht H, Ziehbuhr W, Endres
      M, Laufs R, Gruter L (1994) Antimicrob Agents Chemother 38: 1251-1255]. In the
      present study we compared the beta-lactam susceptibility and the slime production
      capacity of 60 phenotypic variants of S. epidermidis parent strain RP62A
      identified by their colony morphology on congo red agar. We could show that the
      variable degree of slime production is linked to different levels of beta-lactam
      susceptibility in intermediate-stage phase variants. The increased deltahemolysin
      production of slime-negative phase variants may indicate an accessory gene
      regulator-like control.

PMID- 8577311
TI  - Correlation of interstitial pneumonia with human cytomegalovirus-induced lung
      infection and graft-versus-host disease after bone marrow transplantation.
AB  - In a retrospective analysis lung biopsy specimens obtained postmortem from 30
      consecutive allogeneic bone marrow transplant recipients who had died of either
      either interstitial pneumonitis (IP; 18/30 patients) or various other causes
      (12/30 patients) were studied for the local presence of human cytomegalovirus
      (HCMV) by culture, in situ hybridization, polymerase chain reaction (PCR) and
      immunohistochemistry for HCMV proteins. All patients suffering from IP were found
      to be HCMV positive in the lung biopsy. PCR revealed the highest sensitivity for
      HCMV detection in lung biopsies, but in 15/18 PCR-positive samples local HCMV
      infection could be confirmed by at least one additional technique. All the lung
      biopsies obtained from the 12 patients without IP were negative for HCMV by all
      techniques applied, except one with a weak HCMV-DNA signal in the PCR assay. The
      severity of the clinical, as well as histological and immunohistological
      alterations in the lung did not correlate with the amount of HCMV-DNA or the
      number of HCMV-positive cells detected in the biopsy. An increase of HLA-class II
      antigen and of ICAM-1 expression on the alveolar epithelium, as well as presence
      of activated CD8+ or CD4+ lymphocytes infiltrating only HCMV-positive lung
      biopsies revealed T cell-mediated immune reactions to be involved in the
      pathogenesis of IP. Since all analyzed patients presented with severe acute or
      extensive chronic graft-versus-host disease (GvHD), but only those with pulmonary
      HCMV infection developed IP, dissemination of HCMV appears to be the primary
      requirement for the initiation of IP. GvHD, however, may interfere with normal
      control of subsequent antiviral immune response and, thus, provoke the
      immunopathology of IP.

PMID- 8577312
TI  - Interactions of Yersinia enterocolitica with polarized human intestinal Caco-2
      cells.
AB  - The in vitro interactions of Yersinia enterocolitica, Salmonella typhimurium and
      Escherichia coli with polarized human colonic carcinoma (Caco-2) cells are
      described. Invasion of a confluent Caco-2 cell monolayer by Yersinia and
      Salmonella took place within 4 h after contact, which was in marked contrast to
      E. coli which did not invade Caco-2 cells. Cytoplasmic extrusions developed on
      the apical membrane and indicated the site of entrance of bacteria into the Caco
      2 cells. Intracellular Yersinia and Salmonella were surrounded by a vacuolar
      membrane. Single as well as multiple bacteria were enclosed within a single
      vacuole. At 6 h after contact some of the intracellular yersiniae were found free
      in the cytoplasm. Furthermore, morphological signs of degeneration of Caco-2
      cells such as vacuolization and autophagy were observed. Caco-2 cells infected
      with Salmonella also showed degenerative changes but the salmonellae resided
      within membrane-bound vacuoles in contrast to Yersinia. These observations are in
      contrast to those described for the invasion of other cells lines (not derived
      from intestinal epithelium) by Yersinia and may reflect more closely the
      interactions between Yersinia and the intestinal epithelium during
      gastrointestinal infection.

PMID- 8577313
TI  - Follicular dendritic cells productively infected with immunodeficiency viruses
      transmit infection to T cells.
AB  - Lymphoid organs have been proposed to function as the major reservoir for the
      human immunodeficiency virus type 1 (HIV-1). Within lymphatic tissues germinal
      centers represent foci of rapidly proliferating B cells governed by the
      interaction between B and T cells and follicular dendritic cells (FDC).
      Accumulating evidence suggests an important role of FDC in the pathophysiology of
      the acquired immunodeficiency syndrome. Direct proof for the infectibility of FDC
      with HIV-1 has been lacking until recently when we were able to demonstrate a CD4
      independent infection of FDC in vitro. Here we report that in vitro HIV-1
      infected human FDC do not only contain proviral DNA, but also produce the virus,
      and transmit the infection to T cells. Furthermore, electron microscopical
      studies on ex vivo isolated FDC from simian immunodeficiency virus (SIV)-infected
      rhesus monkeys revealed typical virus budding. In addition, FDC from SIV-infected
      rhesus monkeys transmitted the infection to T cells in vitro. Due to this central
      role within the immune response FDC may serve as preferential targets for HIV
      both by trapping of virions on their surfaces and by productive infection. During
      disease FDC become productively infected and may, thus, be regarded as crucial
      elements in viral dissemination.

PMID- 8577314
TI  - Prevalence of Borna disease virus RNA in peripheral blood mononuclear cells from
      blood donors.
AB  - The presence of Borna disease virus (BDV) in peripheral blood mononuclear cells
      (PBMC) of 100 blood donors from Sapporo and 72 blood donors from Tokyo was
      examined using nested reverse transcriptase/polymerase chain reaction
      amplification with specific-primers for BDV p24. Anti-BDV p24 antibodies in the
      plasma of the 100 blood donors from Sapporo also were studied by enzyme-linked
      immunosorbent assay and by Western blot. BDV RNA was detected in 3 (4.2%) of the
      72 PBMC samples from Tokyo, and in 5 (5%) of the 100 PBMC samples from Sapporo.
      In contrast, anti-p24 antibodies were found in only 1 (1%) of the donors from
      Sapporo. These results suggest that BDV infection in humans may be more
      widespread than previously thought.

PMID- 8577315
TI  - Conservation of the organization of the streptokinase gene region among
      pathogenic streptococci.
AB  - Using ten gene-specific probes from the cloned and sequenced streptokinase gene
      (skc) region (8,931 bp) of Streptococcus equisimilis H46A, a human serogroup C
      strain, the conservation of these genes and their linkage relationships were
      studied by Southern hybridization in pathogenic streptococci differing
      taxonomically, serologically, in regard to their host range, and in the class of
      plasminogen activator produced. The results indicate that in S. pyogenes (strains
      A374, NZ131 and SF130/13) and a human group G strain (G19,908) both gene content
      and gene order as determined for H46A (dexB-abc-lrp-skc-orfl-rel) are preserved.
      The same is true of an equine S. equisimilis isolate (87-542-W), the
      streptokinase gene of which has been shown to hybridize detectably with skc, a
      result at variance with that obtained previously by others. In contrast, the
      chromosomal DNA of three S. uberis strains (0140J, C198, C216) of bovine origin,
      two of which produced a plasminogen activator different from streptokinase,
      hybridized only with dexB-, abc- and rel-specific probes, and the homologues of
      these genes appeared to lie close to each other. The maintenance of the
      organization of the streptokinase gene region in strains differing in overall
      chromosomal character suggests that this gene arrangement is of selective
      advantage.

PMID- 8577316
TI  - Binding of outer membrane preparations of Campylobacter jejuni to INT 457 cell
      membranes and extracellular matrix proteins.
AB  - Binding of outer membrane (OM) preparations of the thermophilic Campylobacter
      species C. jejuni to epithelial cell membranes and extracellular matrix proteins
      were studied in an in vitro model system using enzyme-linked immunosorbent assay.
      The OM preparations exhibited significant binding to INT 407 intestinal cell
      membranes. The process of adhesion was modulated by enzymatic, chemical or
      immunological pretreatment of the bacteria. Following oxidation of the
      lipopolysaccharide (LPS) with sodium meta-periodate, the OM preparations
      essentially retained their binding properties. After pretreatment with proteinase
      K, the OM preparations lost their binding capacity and the apparent molecular
      mass of the major OM protein shifted from 42 to 24 kDa. Preincubation of C.
      jejuni bacteria with C. jejuni-specific antiserum reduced adhesion significantly;
      preincubation with LPS-specific monoclonal antibodies only to a minimal extent.
      The OM preparations also bound significantly to the extracellular matrix proteins
      collagen and fibronectin; however, they bound virtually no bovine serum albumin
      or horse serum.

PMID- 8577317
TI  - trans-splicing: an update.
AB  - 5'-end maturation of messenger RNAs via acquisition of a trans-spliced leader
      sequence occurs in several primitive eukaryotes, some of which are parasitic.
      This type of trans-splicing proceeds though a two-step reaction pathway directly
      analogous to that of cis-splicing and like cis-splicing it requires multiple U
      snRNP cofactors. This minireview attempts to provide a brief synopsis of our
      current understanding of the evolution and biological significance of trans
      splicing. Progress in deciphering the mechanism of trans-splicing, particularly
      as it relates to current models of cis-splicing, is also discussed.

PMID- 8577318
TI  - Sequence heterogeneity of the C-terminal, Cys-rich region of the merozoite
      surface protein-1 (MSP-1) in field samples of Plasmodium falciparum.
AB  - Recent results with primate plasmodia and rodent models of infection have focused
      attention on the C-terminal region of the merozoite surface protein-1 (MSP-1) as
      one of the leading candidates for vaccination against the erythrocytic stages of
      malaria. However, sequence heterogeneity of this region may compromise its use as
      a vaccine candidate. While the C-terminal region of MSP-1 from the two prototypic
      alleles of P. falciparum has been shown to be relatively conserved in laboratory
      maintained strains, little data exist on sequence heterogeneity of this region in
      field isolates from diverse geographic areas. To address this question, DNA
      encoding the C-terminal, Cys-rich region of P. falciparum MSP-1 from field
      samples was analyzed by a polymerase chain reaction (PCR)-direct sequencing
      method. Sequence data were consistent with those obtained from laboratory
      maintained strains. In 15 isolates from Africa, Asia and Latin America, only a
      few nucleotide changes were found leading to amino-acid alterations at four
      positions out of 102 residues. All the variations corresponded to the predicted
      amino-acid sequence of the other prototype, suggesting that these changes were
      possibly due to allelic recombinations. The four changes were E-->Q at position
      1644 and TSR-->KNG, or KNG-->TSR at positions 1691, 1700 and 1701. Thus, only
      three patterns of the C-terminal, Cys-rich region of MSP-1, E-TSR, Q-KNG and Q
      TSR, were detected. All the Cys residues were conserved. These results support
      the potential utility of the C-terminal region of MSP-1 as a vaccine candidate.

PMID- 8577319
TI  - Cloning and characterization of a Plasmodium falciparum cyclophilin gene that is
      stage-specifically expressed.
AB  - An immunosuppressive agent, cyclosporin A (CsA), has antimalarial activity in
      several Plasmodium species. Cyclophilins of several species including Plasmodium
      falciparum exhibit peptidyl-prolyl cis-trans isomerase activity which is
      inhibited by CsA. A gene encoding P. falciparum cyclophilin (PFCyP) was cloned
      and characterized. This gene has the entire coding sequence for the mature
      protein plus a 39-amino-acid-long N-terminal extension. Most of the amino acids
      predicted to be involved in the peptidyl-prolyl cis-trans isomerase activity and
      CsA binding are present in the cloned gene. The PFCyP also has the single highly
      conserved tryptophan residue that is a major determinant in the inhibition of
      PPIase activity by CsA. The PFCyP coding sequence with or without the N-terminal
      amino-acid extension was used to construct recombinant expression vectors which
      were transformed into E. coli. Both vectors produced enzymatically active mature
      PFCyP proteins that were sensitive to CsA. Northern blot analysis of RNA isolated
      from the synchronized parasite cultures verified the expression of PFCyP in all
      erythrocytic stages of the parasite, but at variable levels. The highest level of
      expression was observed in ring-stage parasites, a stage shown to be more
      susceptible to CsA. Inhibition of P. falciparum growth in vitro by CsA was re
      evaluated for chloroquine-sensitive and chloroquine-resistant strains of the
      parasite. Essentially, there was no difference between the two strains for the
      concentration of CsA required to yield 50% inhibition in 48 h of exposure (0.25
      0.4 microM).

PMID- 8577320
TI  - Characterization of the gene family encoding a host-protective antigen of the
      tapeworm Taenia ovis.
AB  - Genomic structure has been determined for a gene encoding a host-protective
      antigen of the parasitic platyhelminth Taenia ovis. An incomplete cDNA, known as
      45W, encodes the protective antigen. Southern hybridisation experiments using 45W
      cDNA as a probe, revealed that the 45W gene was a member of a multigene family.
      Differential Southern hybridisation and rapid amplification of cDNA end (RACE)
      experiments were used to characterise the related genes, allowing the full-length
      coding region of the 45W encoded antigen to be determined. The gene family
      comprises a minimum of four members per haploid genome with each member showing
      varying degrees of 5' and 3' homology with respect to the 45W cDNA. A close
      homologue of the 45W gene, designated 45S, differed from 45W at 11 of 985 nt
      comprising the full-length mRNA. Sequencing of several independent RACE products
      for both 45W and 45S identified a cDNA which may be a product of homologous
      recombination between these genes, suggesting that the two genes may be alleles.
      Homologous recombination in genes which encode a host protective antigen such as
      45W would provide a mechanism by which antigenic variants could arise.

PMID- 8577321
TI  - Cloning and expression of the hypoxanthine-guanine phosphoribosyltransferase from
      Leishmania donovani.
AB  - The gene encoding the hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
      enzyme from Leishmania donovani has been cloned and sequenced. The hgprt open
      reading frame encoded a polypeptide of 211 amino acids that exhibited 3 regions
      of significant homology with other eukaryotic HGPRTs and a C-terminal tripeptide
      compatible with a glycosomal targeting signal. Northern blot analysis of L.
      donovani RNA revealed two hgprt transcripts, a 1.9-kb mRNA and a 1.7-kb
      transcript. The expression of the 1.7-kb hgprt mRNA and the activity of HGPRT
      enzyme were both augmented approx. 5-fold in parasites incubated in the absence
      of purines. Southern blots of genomic DNA indicated only a single hgprt locus
      within the L. donovani genome. Overexpression of L. donovani hgprt in E. coli
      complemented genetic deficiencies in hypoxanthine and guanine phosphoribosylating
      activities and yielded abundant quantities of enzymatically active HGPRT. The
      recombinant HGPRT was purified to homogeneity and recognized hypoxanthine,
      guanine and allopurinol, but not adenine or xanthine, as substrates. The hgprt
      clone and pure HGPRT protein provide essential reagents for validating HGPRT as a
      therapeutic target for the treatment of leishmaniasis and other diseases of
      parasitic origin.

PMID- 8577322
TI  - Intergenic region typing (IRT): a rapid molecular approach to the
      characterization and evolution of Leishmania.
AB  - In the New World, Leishmania of the Viannia subgenus cause both cutaneous and
      mucocutaneous disease. These parasites show considerable intra-species genetic
      diversity and variation, which complicates taxonomic classification and
      epidemiology. We have used the variability of the transcribed noncoding regions
      between the small and large subunit rRNA genes to examine relationships in this
      group. In a method termed intergenic region typing (IRT), PCR amplification
      products were obtained for the rapidly evolving 1-1.2-kb internal transcribed
      spacers (ITS) between the SSU and LSU rRNAs, from 50 parasites isolated from
      different hosts and geographic areas. Amplified DNAs were digested with 10
      different enzymes, and fragment patterns compared after acrylamide gel
      electrophoresis. High levels of intra- and inter-specific variation were
      observed, and quantitative similarity comparisons were used to associate
      different lineages. A complex evolutionary tree was obtained. Some species formed
      tight clusters (L. equatorensis, L. panamensis, L. guyanensis, L. shawi), while
      L. braziliensis was highly polymorphic and L. naiffi showed intraspecific
      distances comparable to the largest obtained within all Viannia. L. colombiensis,
      L. equatorensis and L. lainsoni clearly represent distinct lineages. Good
      agreement was obtained with molecular trees based upon isoenzyme or mini-exon
      repeat sequence comparisons. Overall, IRT appears to be a superb method for
      epidemiological and taxonomic studies of Leishmania, being sensitive, rapid and
      quantitative while simultaneously revealing considerable molecular diversity. IRT
      could also be applied to other nonconserved intergenic regions, including those
      separating protein-coding genes.

PMID- 8577323
TI  - Characterization of a plasminogen activator produced by Acanthamoeba castellanii.
AB  - Serine proteases play an important role in a diverse array of biological
      processes, including embryogenesis, metastasis, angiogenesis, thrombolysis and
      tissue invasion by certain parasites. The latter observation prompted us to
      explore the possibility that the tissue-invasive ocular parasite Acanthamoeba
      castellanii elaborates one or more serine proteases. Acanthamoeba sp. are
      pathogenic free-living amoebae that can produce an invasive, blinding
      inflammatory disease of the cornea, termed Acanthamoeba keratitis. The present
      study reports the preliminary purification and characterization of a novel
      plasminogen activator from an ocular isolate of A. castellanii. The parasite
      derived enzyme has a molecular mass of approx. 40 kDa and produces a single band
      of lysis on fibrinogen-agarose zymographs. Activity of the enzyme is completely
      inhibited by treatment with diisopropylfluorophosphate, indicating that it is a
      serine protease. The parasite-derived serine protease is not inhibited by
      amiloride which is a strong inhibitor of urokinase-type plasminogen activator.
      Additionally, the enzyme is not inhibited by plasminogen activator inhibitor-1
      which is the primary physiological inhibitor of both urokinase and tissue-type
      plasminogen activator. It does not cross-react with antibodies specific for human
      urokinase or tissue-type plasminogen activator. The parasite-derived enzyme
      activates plasminogen from several mammalian species, including human, cow and
      pig. Thus, it is possible that this parasite-derived serine protease contributes
      to the pathogenesis of Acanthamoeba keratitis.

PMID- 8577325
TI  - Exogenous and endogenous sources of sterols in the culture-adapted procyclic
      trypomastigotes of Trypanosoma brucei.
AB  - The growth of the culture-adapted procyclic forms of Trypanosoma brucei
      (procyclics) is accelerated by supplementation of the medium with low-density
      lipoprotein (LDL) particles. This effect can be attributed to receptor-mediated
      endocytosis of LDL, followed by utilization of lipids carried by the
      lipoproteins. Indeed, procyclics that normally contain ergosterol synthesized de
      novo, also incorporate exogenous cholesterol in their membranes. In turn, import
      of exogenous lipids down-regulates the isoprenoid biosynthetic machinery as
      measured by a approx. 3-fold decrease of [14C]acetate incorporation into sterols
      and a approx. 2-fold decrease of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase activity, compared with cells grown in lipoprotein-depleted medium.
      Synvinolin, a specific inhibitor of HMG-CoA reductase that slows down the
      procyclic growth in vitro and decreases [14C]acetate incorporation into sterols,
      produces striking morphological modifications, including an arrest at cytokinesis
      and an extensive swelling of the kinetoplast-mitochondrion system. These
      cytotoxic effects are amplified in the absence of lipoprotein supply. In
      conclusion, procyclics may acquire sterols from both exogenous and endogenous
      sources. To a large extent, these two pathways compensate each other,
      illustrating adaptation of the parasites to survive in extremely different
      environments.

PMID- 8577324
TI  - Structure and sequence variation of the genes encoding the polymorphic,
      immunodominant molecule (PIM), an antigen of Theileria parva recognized by
      inhibitory monoclonal antibodies.
AB  - The polymorphic, immunodominant molecule (PIM) of Theileria parva is the
      predominant antigen recognized by sera from infected cattle and by monoclonal
      antibodies (mAb) used to differentiate parasite strains. As such, the antigen is
      under consideration as a diagnostic antigen, and since the mAbs can neutralize
      sporozoite infectivity in vitro, in immunization experiments. Initial comparison
      of two PIM cDNA sequences suggested that the PIM genes consist of conserved 5'
      and 3' termini flanking a central variable region. We present further evidence,
      based on sequence analysis, supporting this general structure for the PIM genes.
      Evidence is also presented for a single copy of the PIM gene per haploid genome,
      implying that the different versions of PIM are encoded by distinct alleles. The
      central variable region of the PIM allele from the T. parva (Marikebuni) stock
      was found to contain 13 copies of the tetrapeptide repeat Gln-Pro-Glu-Pro. We
      also detected point mutations in the 5' and 3' termini of the PIM alleles,
      including regions recognized by the neutralizing and typing mAb. This contrasted
      with the high sequence conservation of the two introns of the genes, suggesting
      that the protein is undergoing rapid evolution. Sequence comparison of PIM genes
      from buffalo- and cattle-derived parasites supported earlier results that the
      parasites infecting buffaloes constitute a more heterogeneous population than
      those from cattle.

PMID- 8577326
TI  - Molecular analysis of two hexokinase isoenzymes from Entamoeba histolytica.
AB  - The zymodemes, electrophoretic patterns of hexokinase, phosphoglucomutase and
      glucose phosphate isomerase isoenzymes, have been widely used to determine the
      pathogenicity of Entamoeba histolytica isolates. Although pathogenic and
      nonpathogenic forms of E. histolytica differ clearly in sequences of many
      homologous genes, a conversion between pathogenic and nonpathogenic zymodemes has
      been reported by several laboratories. To approach the question what might be the
      basis for the observed conversion, we examined the molecular biology of the
      hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) isoenzymes in
      pathogenic E. histolytica. We isolated two different cDNAs pHXK1 and pHXK2 coding
      for polypeptides with significant sequence similarity to hexokinases and deduced
      molecular masses of 49.8 kDa and 49.4 kDa. The two hexokinase sequences differed
      by 11% on the amino acid and by 8% on the nucleotide level. Expression of the
      cDNAs in Escherichia coli as nonfusion proteins gave two polypeptides with
      hexokinase activity. The recombinant Hxk1 and Hxk2 polypeptides comigrated with
      the more basic and more acidic isoforms of pathogenic amoebae in starch gel
      electrophoresis, as well as in low and high resolution isoelectric focussing
      gels. This identified the observed hexokinase isoenzymes of pathogenic E.
      histolytica as the products of two genes, hxk1 and hxk2.

PMID- 8577327
TI  - Identification and analysis of the start site of ribosomal RNA transcription of
      Entamoeba histolytica.
AB  - In this article we report the identification of the start site of ribosomal RNA
      transcription unit of the enteric parasite E. histolytica. We cloned the upstream
      region of the ribosomal RNA and we defined the 5' boundary of the transcription
      unit with nuclear run-on assays. We report that ribosomal transcription starts
      2447 bp upstream the SSU ribosomal gene, at an adenosine residue. This data was
      supported both by S1 mapping and by primer extension analysis; that the mapped
      site was indeed the transcription start point was demonstrated by RNAse
      protection of the in vitro capped RNA. Our sequence data around the transcription
      start point shows two different tandem repeat clusters immediately downstream
      from the transcription start point.

PMID- 8577328
TI  - Modification of the sterol composition of Trypanosoma (Schizotrypanum) cruzi
      epimastigotes by delta 24(25)-sterol methyl transferase inhibitors and their
      combinations with ketoconazole.
AB  - We report a detailed analysis of the sterol composition of Trypanosoma cruzi
      epimastigotes grown in the absence or presence of two sterol analogs previously
      reported as inhibitors of delta 24(25) sterol methyltransferase (24(25)
      SMT,E.C.2.1.1.43) in yeast and fungi, a cholestanol analog with a 6-membered aza
      ring as side chain (22,26-azasterol) and 24-(R,S),25-epiminolanosterol, as well
      as combinations of these compounds with the C14 demethylase inhibitor
      ketoconazole. Both sterol analogs produced a dose-dependent reduction in the
      incorporation of radioactivity from [methyl-14C]methionine with IC50 values of
      640 nM and 70 nM for 22,26-azasterol and 24,25-(R,S)-epiminolanosterol,
      respectively, indicating a specific inhibition of 24(25)-SMT. Correspondingly, it
      was found that the sterols present in control cells (ergosterol, 24-ethylcholesta
      5,7,22-trien-3 beta-ol and precursors) were almost completely replaced by
      zymosterol (cholesta-8,24-dien-3 beta-ol) or a mixture of zymosterol, cholesta
      7,24-dien-3 beta-ol and cholesta-5,7,24-trien-3 beta-ol when the parasites were
      exposed to the minimal growth inhibitory concentrations of 22,26-azasterol and 24
      (R,S),25-epiminolanosterol, respectively. At sub-optimal concentrations of the
      inhibitors a complete disappearance of the 24-ethyl sterols was observed and a
      concomitant increase in the proportion of 24-methyl sterols, particularly delta
      24(24') sterols. This showed that in T. cruzi the second methenylation step
      (catalyzed by delta 24(24') sterol methyl transferase) was significantly more
      sensitive to these inhibitors than the first and that the sterol analogs were
      also powerful inhibitors of the delta 24(24') sterol reductase. In growth
      arrested epimastigotes resulting from their treatment with low (1-3 microM)
      concentrations of either sterol analog combined with sub optimal (100-300 nM)
      levels of ketoconazole the main sterol was lanosterol with no evidence 24
      methylenedihydrolanosterol, the main sterol found in cells treated with growth
      inhibitory concentrations of the azole alone. Taken together, these results
      indicated that 24-alkyl sterols are essential growth factors for T. cruzi and
      that the preferred substrate of the delta 24(25) sterol methyl transferase in
      this organism is zymosterol.

PMID- 8577329
TI  - A possible role for the guide RNA U-tail as a specificity determinant in
      formation of guide RNA-messenger RNA chimeras in mitochondrial extracts of
      Crithidia fasciculata.
AB  - Chimeric g(uide) RNA:pre-mRNA molecules are potential intermediates of the RNA
      editing process in kinetoplastid mitochondria. We have studied the
      characteristics of chimeric molecules formed in mitochondrial extracts of the
      insect trypanosomatid Crithidia fasciculata which had been supplied with
      synthetic NADH dehydrogenase (ND) subunit-7 gRNA and pre-mRNA variants. The
      ability of a gRNA to participate in chimera formation in this system depends on
      the possibility of base pairing with the pre-mRNA via the anchor sequence, but
      not on the presence of a U-tail or a full-length informational part. Chimeras
      formed with a specific gRNA:pre-mRNA pair displayed a large variation in length,
      due to variably sized 3' end truncations of the gRNA moieties and variation in
      the sites in the pre-mRNA to which the gRNAs were attached. Surprisingly, the
      presence of a U-tail in the gRNA for a large part determined the specificity of
      the linkage. In 60% of the cases gRNAs possessing a U-tail of at least one
      residue were attached to an editing site, whereas 75% of the gRNAs without Us
      were attached to non-editing sites. Furthermore, the chimera forming activity was
      greatly stimulated by the addition of ATP but not by AMP-CPP, an ATP-analogue
      with a non-hydrolyzable alpha-beta phosphate bond. This suggests the involvement
      in the chimera formation of an RNA ligase.

PMID- 8577330
TI  - A diamidine-resistant Trypanosoma equiperdum clone contains a P2 purine
      transporter with reduced substrate affinity.
AB  - Following the demonstration that the transport of melaminophenyl arsenical drugs
      in Trypanosoma brucei is dependent upon an unusual adenosine nucleoside
      transporter (Carter and Fairlamb, Nature 361 (1993) 173-175) we have investigated
      adenosine transport in the related parasite Trypanosoma equiperdum (Botat1.1) and
      a cloned derivative resistant to the diamidine drug berenil (diminazene
      aceturate) with limited cross-resistance to the melaminophenyl arsenical
      cymelarsen. The parental strain possesses a bipartite adenosine transport system
      consisting of one component which is inhibited in a dose-dependent and saturable
      manner with increasing concentrations of inosine and a second component which is
      similarly inhibited by adenine. Uptake of adenosine on this second transporter is
      also inhibited in a dose-dependent fashion by berenil and cymelarsen. Both
      transporters have high affinity for adenosine (apparent Km values of 0.60 and
      0.70 mM and Vmax values of 8.4 and 6.9 pmol (s (10(8) trypanosomes))-1 at 25
      degrees C, respectively). Thus T. equiperdum shares with T. brucei a system
      comprising two adenosine transporters named P1 and P2, respectively. The P1
      transporter is similar in the sensitive and resistant T. equiperdum clones,
      whereas the P2 transporter has reduced transport capacity at physiological
      adenosine concentration and decreased affinity for adenosine in the drug
      resistant clone.

PMID- 8577331
TI  - Molecular characterization of a Brugia malayi intermediate filament protein which
      is an excretory-secretory product of adult worms.
AB  - Filarial parasites release macromolecules into their environment both in vitro
      and in vivo. These excretory-secretory products (E-S) have been studied with
      respect to function, vaccination potential, pathogenicity, and ability to serve
      as antigen targets for diagnostic tests. We have recently described monoclonal
      antibody OV-1 which binds to an intermediate filament in E-S and circulating
      antigens of Onchocerca volvulus. OV-1 also binds to cross-reactive antigens of
      Brugia malayi. Therefore, OV-1 was used to immunoscreen a B. malayi adult worm
      cDNA library in an attempt to clone a homologue (BMIF). BMIF is a 1664-bp full
      length transcript which codes for 505 amino acids. BMIF has 95% sequence homology
      at the amino-acid level to OV1CF, an O. volvulus intermediate filament that was
      also selected with OV-1, and 75% homology to Ascaris intermediate filament A.
      Southern blot analysis suggests that BMIF is confined to a single location in the
      genomic DNA of B. malayi. Antibodies raised to BMIF identified native antigens in
      immunoblots of B. malayi adult worms, infective larvae and adult E-S. In
      addition, the antibody also bound to a 60-kDa antigen in immunoblots of
      poly(ethylene glycol)-precipitated immune complexes in sera from B. malayi
      infected patients. Localization studies showed that the antigen encoded by BMIF
      is present in the hypodermis, developing embryos and muscle of adult B. malayi.
      These studies show that BMIF is an E-S product of B. malayi adult worms which is
      detectable in sera from patients with brugian filariasis.

PMID- 8577332
TI  - A direct and rapid sequencing strategy for the Plasmodium falciparum antigen gene
      gp190/MSA1.

PMID- 8577333
TI  - Sequence and genomic organisation of a novel repetitive DNA element from the
      potato cyst nematode Globodera pallida.

PMID- 8577334
TI  - Phylogenetic relationships between Old World Leishmania strains revealed by
      analysis of a repetitive DNA sequence.

PMID- 8577336
TI  - Transcription of protein-coding genes in Entamoeba histolytica is insensitive to
      high concentrations of alpha-amanitin.

PMID- 8577335
TI  - Cloning of a bradyzoite-specific gene of Toxoplasma gondii encoding a cytoplasmic
      antigen.

PMID- 8577337
TI  - Developmental regulation of Taenia ovis 45W gene expression.

PMID- 8577338
TI  - Sequence analysis of apical membrane antigen 1 (AMA-1) of Plasmodium cynomolgi
      bastianelli.

PMID- 8577339
TI  - Isolation of lmcpc, a gene encoding a Leishmania mexicana cathepsin-B-like
      cysteine proteinase.

PMID- 8577340
TI  - Stage-specific expression of the mRNA encoding a 14-3-3 protein during the life
      cycle of Schistosoma mansoni.

PMID- 8577341
TI  - Marine fish and ray trypanosomes have large kinetoplast minicircle DNA.

PMID- 8577342
TI  - Ca2+ signal induced by Trypanosoma cruzi metacyclic trypomastigote surface
      molecules implicated in mammalian cell invasion.

PMID- 8577343
TI  - A bradyzoite stage-specifically expressed gene of Toxoplasma gondii encodes a
      polypeptide homologous to lactate dehydrogenase.

PMID- 8577344
TI  - Molecular analysis of antigens targeted by protective antibodies in rapid
      expulsion of Trichinella spiralis [Mol. Biochem. Parasitol. 65 (1994) 201].

PMID- 8577345
TI  - Characterization of arachidonic-acid-metabolizing enzymes in adult Schistisoma
      mansoni.
AB  - Schistosoma mansoni has previously been reported to synthesize a wide range of
      eicosanoids including prostaglandins, leukotrienes and hydroxyeicosatetraenoic
      acids (HETEs). Our analysis of arachidonic acid metabolites synthesized by
      microsomal and cytosolic extracts from adult S. mansoni using thin-layer
      chromatography and radioimmunoassay techniques indicate the presence of a
      soluble, enzymatically active lipoxygenase (Lox) and the absence of any
      cyclooxygenase (Cox) activity. The S. mansoni Lox activity catalyzed the
      formation of a 15-hydroxyeicosatetraenoic acid (15-HETE)-like species. This
      activity was calcium-independent and inhibitable by inhibitors of mammalian and
      plant Lox. The conversion of linoleic acid to a 13-hydroxyoctadecadienoic acid
      (13-HODE)-like product by S. mansoni extracts indicates that the parasite Lox
      homologue is similar to mammalian 15-Lox. Immunoblot analysis of S. mansoni
      extracts using antisera to different mammalian lipoxygenases detects two
      immunoreactive proteins with molecular weights similar to plant and mammalian
      lipoxygenases. In addition, polymerase chain reaction (PCR) amplification of Lox
      like sequences from S. mansoni genomic DNA using degenerate primers based on
      conserved plant and mammalian Lox sequences, generated two PCR products which
      hybridized to a human 15-Lox cDNA probe. While the role of eicosanoid production
      in the physiology of S. mansoni is not known, eicosanoids may be essential for
      normal physiological processes as is the case in other invertebrates.
      Interestingly, 15-HETE has previously been shown to have immunosuppressive
      effects in mammals, and this may be related to the ability of the parasite to
      overcome host immune responses.

PMID- 8577346
TI  - Kinetic mechanism of pyrophosphate-dependent phosphofructokinase from Giardia
      lamblia.
AB  - The steady-state kinetics of the reaction catalyzed by inorganic-pyrophosphate
      dependent D-fructose-6-phosphate 1-phosphotransferase from Giardia lamblia have
      been investigated. The reactants for the forward and reverse reactions were the
      Mg-chelated complexes of pyrophosphate (PPi) and Pi. Uncomplexed ligands were not
      substrates. In the direction of phosphorylation of fructose-6-phosphate (F6P),
      initial velocity double-reciprocal plots for both PPi and F6P were intersecting
      suggesting sequential addition of substrates. Similarly, intersecting patterns
      were observed in the reverse reaction with either Pi or fructose-1,6-bisphosphate
      (FBP) as the variable substrate. Although the catalytic constants for the forward
      and reverse reactions were found to be identical (83 s-1), the kcat/Km for PPi is
      about two orders of magnitude higher than the kcat/Km for Pi, indicating that PPi
      is utilized much more efficiently than Pi. Product inhibition of Pi is
      competitive vs. PPi and noncompetitive vs. F6P, when the fixed substrate is
      subsaturating. Product inhibition by FBP was found to be noncompetitive with
      either Pi or F6P as the variable substrate. These results are consistent with a
      sequential ordered Bi Bi mechanism with PPi adding first and Pi dissociating
      last. In the reverse reaction, however, PPi and F6P were found to be
      noncompetitive with either Pi or FBP. Dead-end inhibition analysis with fructose
      2,6-bisphosphate, a competitive substrate analog of FBP, gave uncompetitive
      inhibition with respect to Pi, indicating that fructose 2,6-bisphosphate (and
      hence FBP) binds after Pi. This kinetic mechanism is different from that observed
      with the enzyme from Propionibacterium freudenreichii, Entamoeba histolytica or
      Mung bean, which were concluded to be rapid equilibrium random mechanism.

PMID- 8577347
TI  - Purification and characterization of a beta-like DNA polymerase from Trypanosoma
      cruzi.
AB  - A DNA polymerase was purified to near homogeneity from Trypanosoma cruzi
      epimastigotes. This preparation had a major polypeptide of 50 kDa and a minor
      band of 45 kDa. SDS-PAGE studies and a novel colorimetric activity gel technique
      demonstrated that the 50-kDa polypeptide chain is the catalytic subunit of this
      T. cruzi DNA polymerase. Western blot analysis of different purification stage
      fractions strongly suggests that this 50-kDa protein is the intact catalytic
      subunit and does not correspond to a degradation product from a larger one. This
      T. cruzi DNA polymerase is insensitive to aphidicolin, butylphenyldeoxyguanosine
      triphosphate, berenil, ethidium bromide and N-ethylmaleimide, but is markedly
      inhibited by the dideoxythymidine triphosphate analogue. Studies with different
      DNA templates showed that the DNA polymerase prefers activated DNA as substrate
      and that it cannot elongate oligoriboadenylate primers. The data presented in
      this paper are consistent with the hypothesis that this enzyme corresponds to a
      beta-like DNA polymerase present in the parasitic protozoon T. cruzi.

PMID- 8577348
TI  - Chromosome specific markers reveal conserved linkage groups in spite of extensive
      chromosomal size variation in Trypanosoma cruzi.
AB  - The karyotypes of three cloned stocks, CL Brener (CL), CA I/72 (CA) and Sylvio
      X10/7 (X10), of Trypanosoma cruzi were studied by pulsed-field gel
      electrophoresis followed by ethidium bromide staining and hybridization with 35
      different probes, 30 of which identified single chromosomes. The chromosome
      specific probes identified between 26 and 31 chromosomal bands in the three
      cloned stocks, corresponding to 20 unique chromosomes in CL and 19 in CA and X10.
      Considering the DNA content of the parasite, it was predicted that the markers
      recognise at least half of all T. cruzi chromosomes. A majority of identified
      chromosomes showed large differences in size among different strains, in some
      cases by up to 50%. Interestingly, CL had in general larger chromosomes than the
      two other studied cloned stocks. Several of the markers showed linkage and nine
      different linkage groups were identified, each comprising 2-4 markers. The
      linkage between the markers was maintained in 8 of the 9 linkage groups when a
      panel comprising 26 different T. cruzi strains representing major T. cruzi
      populations was tested. One linkage group was found to be maintained in some
      strains but not in others. This result shows that chromosomal rearrangements
      occur in the T. cruzi genome, albeit with a low frequency. Repetitive DNA, both
      non-coding and in one case coding, was more abundant in the cloned stock CL
      Brener than in CA and X10. The information presented will make it possible to
      select chromosomes for the construction of physical chromosomal maps required for
      the T. cruzi genome project.

PMID- 8577349
TI  - Sequence, characterization and localization of a cysteine proteinase cathepsin L
      in Schistosoma mansoni.
AB  - A cDNA encoding Schistosoma mansoni cathepsin L was isolated from a cDNA library
      and sequenced. Alignment of the proposed amino-acid sequence with known members
      of cathepsin L shows highest homologies with sequences from mouse and rat. An
      expression plasmid was constructed in Escherichia coli to produce recombinant
      schistosome cathepsin L with an extension of six histidines at its N terminus.
      Using antibodies raised against the purified fusion protein, two polypeptide
      bands with approx. molecular masses of 38 and 31 kDa were identified in a
      schistosome extract. By use of specific radioiodinated inhibitors, a
      radioactively labeled protein could be detected at 31 kDa, suggesting that this
      is the active mature enzyme. The larger protein of 38 kDa did not react with the
      inhibitor, indicating that it represents the inactive precursor molecule.
      Immunohistological experiments revealed that the proteinase is localized in
      structures associated with the reproductive system of females and with the
      subtegumental region of the gynecophoric canal of males. However, Northern blot
      hybridization demonstrates that more transcripts are present in female parasites
      than in males. Genomic Southern blotting suggests that schistosome cathepsin L is
      expressed from a single-copy gene.

PMID- 8577350
TI  - cDNA expressed sequence tags of Trypanosoma brucei rhodesiense provide new
      insights into the biology of the parasite.
AB  - A total of 518 expressed sequence tags (ESTs) have been generated from clones
      randomly selected from a cDNA library and a spliced leader sub-library of a
      Trypanosoma brucei rhodesiense bloodstream clone. 205 (39%) of the clones were
      identified based on matches to 113 unique genes in the public databases. Of
      these, 71 cDNAs display significant similarities to genes in unrelated organisms
      encoding metabolic enzymes, signal transduction proteins, transcription factors,
      ribosomal proteins, histones, a proliferation-associated protein and thimet
      oligopeptidase, among others. 313 of the cDNAs are not related to any other
      sequences in the databases. These cDNA ESTs provide new avenues of research for
      exploring both the novel trypanosome-specific genes and the genome organization
      of this parasite, as well as a resource for identifying trypanosome homologs to
      genes expressed in other organisms.

PMID- 8577351
TI  - Phosphoenolpyruvate carboxykinase from Trypanosoma cruzi. Purification and
      physicochemical and kinetic properties.
AB  - Phospho enolpyruvate carboxykinase (PEPCK) has been purified to homogeneity from
      epimastigotes of the Tul 0 strain of Trypanosoma cruzi. The physicochemical
      parameters determined allowed the calculation of an average molecular mass of 120
      kDa; the subunit molecular mass, about 61 kDa, is in good agreement with the
      value of 58.6 kDa recently determined from the sequence by Sommer et al. (FEBS
      Lett. 359 (1994) 125-129). The PEPCK from T. cruzi presented, in addition to its
      molecular mass, typical properties of other ATP-linked PEPCKs, namely strict
      specificity for ADP in the carboxylation reaction and lower specificity in the
      decarboxylation and exchange reactions, and synergistic activation by CdCl2 or
      MgCl2 when added in addition to MnCl2. The enzyme presented hysteretic behaviour,
      shown by a lag period in the carboxylation reaction, which was affected by
      dilution and preincubation. The decarboxylation reaction catalyzed by the T.
      cruzi PEPCK was not inhibited by excess of ATP-Mn. The apparent Km values for the
      carboxylation reaction, including the low value for PEP (0.035 mM) are compatible
      with an important role of PEPCK, as suggested by previous NMR experiments, on the
      CO2 fixation in vivo which leads to succinate excretion during aerobic
      fermentation of glucose.

PMID- 8577352
TI  - [Intra-extracranial meningioma in the cranial vault].
AB  - Between 1982 and 1993, 11 cases of intra-extracranial vault meningiomas were
      treated in Creteil, by the same multidisciplinary team. The average age was 53.5
      years and the Karnofsky rating was high (> 80 in 7 cases). Ten of the 11 cases
      had medial tumours with venous sinus thrombosis occurring in 9 of these. The
      location of the tumour was frontal in 6 and parietal in 4 patients. Of the medial
      tumours, 5 (half) were bilateral intracranial lesions. The average duration of
      symptoms was more than 10 years in four cases, between 1 and 3 years in five, and
      the diagnosis was made immediately in two patients. MRI coronal sections, after
      venous contrast injection, allowed diagnosis of the lesion and visualisation of
      the sinus thrombosis. Embolisation was performed pre-operatively in all cases
      scheduled to have surgery, resulting in safe excision of the tumour. Surgery was
      performed in 9 patients with complete tumour removal achieved in 8. Of those who
      did not undergo surgery, one received radiotherapy and the other died before
      treatment. The bony defect was covered with cadaveric bone, autogenous bone,
      coral and methyl-methacrylate in one, two, two and two patients respectively.
      Complications occurred in 2 cases: extradural secondary infection and CSF
      rhinorrhea treated with a lumbo-peritoneal shunt. The post-operative Karnofsky
      rating was greater than 90 in seven cases, 70 in one, and 50 in two cases. After
      an average follow-up of 4 years, 3 patients had tumor recurrence at 4, 7, and 8
      years; the first having a locally malignant character, the second showing
      radiological recurrence in a case of subtotal removal, and the third a marginal
      recurrence. Two of the 3 patients underwent further surgery. The malignant case,
      received radiotherapy but unfortunately a new recurrence occurred 14 months
      later. As radiotherapy was used in only 3 cases, statistically significant
      conclusions concerning efficacy cannot be drawn.

PMID- 8577353
TI  - [Nasofrontal dermoid fistulae and cysts. Apropos of 19 cases].
AB  - A series of 19 children with congenital nasal dermoid cyst or fistulas admitted
      in our department between 1978 and 1992 was reviewed in a retrospective study.
      They were 8 females and 11 males, ages ranged from 9 months to 7 years (mean: 2
      years and 4 months). At diagnosis 8 children presented with infection
      (superficial in 6 cases, neurological in 2 cases), and in 11 cases the
      malformation was discovered by the family physician. In 14 cases the cyst was
      located at the mid nasal ridge. Four children had associated malformations:
      neurodevelopmental delay (2 cases), hypertelorism (1 case) and external ear
      agenesia with facial palsy. The cyst was subcutaneous in 5 cases and was operated
      on through a nasal approach. The 14 other children were operated through
      associated intra and extracranial approaches. Surgical exploration disclosed a
      dural extension of the fistula in 9 cases. When performed, preoperative
      radiological explorations including CT Scan and/or MRI had not always predicted
      the dural extension. The mean follow-up is 5.3 years. No recurrence was recorded
      and the cosmetic result was always excellent. Preoperative radiological
      investigations are necessary to precise the location of these malformations and
      to detect associated disorders, but they appear unable to prove the extension of
      the fistula to the dura. Intracranial and extracranial approaches should be
      always planned to perform a total excision of the lesion.

PMID- 8577354
TI  - [Levels of C-reactive protein and complement 4 fraction in hyperthermia secondary
      to microsurgical vascular decompression for trigeminal neuralgia].
AB  - Serial tests for serum C-reactive protein (CRP) and C4 levels were carried out on
      20 patients undergoing microvascular decompression (MVD) for trigeminal neuralgia
      with interposition of synthetic material (Teflon +/- Dacron). These proteins
      represent important elements of host defense mechanisms against invading
      pathogens and their serum levels might be of value in distinguishing bacterial
      meningitis from tissue reaction to synthetic material. According to post
      operative pyrexia, patients were classified into three groups: gr 1 (n = 4):
      apyrexia, gr 2 (n = 11): pyrexia from 38 degrees C to 39 degrees C, gr 3 (n = 5):
      pyrexia upper 39 degrees C. Such frequent hyperpyrexia provides a clinical
      dilemma about meningitis. In 2 patients high CRP levels, 4 days after surgery,
      indicated the presence of meningitis. In all other patients, CRP levels were
      decreasing rapidly and normal levels were reached by day 8. All C4 levels were
      normal values. Measurements of CRP contributed to diagnose common meningitis
      reactions. These reactions seemed more frequent with Dacron and Teflon than with
      Teflon alone. Though non significative this difference deserves confirmation by
      fuller investigations.

PMID- 8577355
TI  - [Microsurgical treatment of trigeminal neuralgia. A study of 50 cases].
AB  - The authors present a study of 50 patients with trigeminal neuralgia treated by
      posterior fossa microsurgery. Microvascular decompression of the trigeminal nerve
      was performed in 48 patients. In 2 cases no neuro-vascular compression was found,
      and a partial rhizotomy was carried out. In 98% of the cases there was
      postoperative abolition of the pain. Two cases of wound infection and three CSF
      fistulas were the operative complications. These patients were reoperated and
      cured. Twenty five patients were reviewed between 13 months and 8 years after
      surgery. Twenty one remained painfree without any drug, 3 were painfree taking
      200 to 400 mg Carbamazepineper day, and 1 patient was reoperated after two years
      without pain because of recurrence of the neuralgia. There was no mortality or
      major morbidity in this series. Our results and the literature concerning this
      method are discussed in this article. In conclusion, microvascular decompression
      may be indicated in a large number of patients with essential trigeminal
      neuralgia due to its excellent pain control, no mortality and low morbidity.

PMID- 8577356
TI  - [Chondrosarcoma of the skull base. Apropos of sphenotemporal localization and
      review of the literature].
AB  - The authors report a case of chondrosarcoma of the skull base with a myxoid
      histology, developed from the right sphenotemporal junction. Twenty six months
      after enlarged tumour removal, there are no clinical or neuroradiological signs
      of recurrence. A review of the 180 published cases emphasizes the rarity of this
      tumour originating of the skull base synchondrosis and occurring in young
      patients. MRI forms the basis of the topographic work-up but does not formally
      distinguish it from chordoma. Diagnosis is confirmed by histology which
      establishes a prognostic scale. Immunohistochemistry eliminates chondroid
      chordoma by demonstrating a mesenchymatous phenotype. Only enlarged tumour
      removal can prolong survival even though improvements have been made in high
      energy radiation therapy and radiosurgery. Cases of recurrence or rare metastasis
      are probably due to incomplete exeresis and in most cases linked to high grade
      histology tumours.

PMID- 8577357
TI  - [Cervical spinal cord compression caused by ossification of the posterior
      vertebral ligament. Apropos of a case].
AB  - Progressive cervical myelopathy due to an ossification of the posterior
      longitudinal ligament (OPLL) appeared in a sicilian women. Diagnosis was made by
      lateral conventional tomograms and CT Scan with mielography. Corporectomy of the
      5th vertebra and ablation of the ligament dramatically improved the clinical
      symptoms. If OPLL seems a common cause of cervical myelopathy in Japan, it is
      very rate in Caucasian people. Instead of the origin of the patients, progressive
      tetraparesis of the 60 years old people is the usual presentation of this
      affection. The cause of OPLL remains unknown: genetic factors, vitamin A,
      association with diffuse idiopathic skeletal hyperostosis, calcium metabolism
      abnormalities are discussed. As far as surgical treatment is concerned, choice
      between anterior and posterior decompression is clarified on the basis of the
      type and the extension of OPLL.

PMID- 8577358
TI  - [Secondary intraspinal localizations of glioblastoma. Apropos of a case].
AB  - Metastasis of intracranial glioblastomas have been described for the first time
      more than fifty years ago. They are exceptional and seem to develop clinically in
      less than 2% of cases. In fact, microscopic metastasis (necropsic series) of such
      glioblastomas are much more frequent: from 6% for supratentorial glioblastomas to
      60% in infratentorial ones; but patients usually die before clinical symptoms
      appear. The authors report on an intraspinal metastasis which appeared clinically
      four years after the removal of a frontal glioblastoma. The metastasis was
      subdural, T3. Preoperative radiological data (CT-scan, MRI) evoked a meningioma,
      while surgical findings favoured the diagnosis of neurinoma. The diagnosis of
      glioblastoma metastasis was suggested by intra-operative pathological findings,
      and confirmed a few days later on smears and stains studies.

PMID- 8577360
TI  - [Stress-induced pituitary apoplexy in 2 phases].
AB  - A case of pituitary apoplexy occurring in the context of physical effort is
      reported. A 47-year-old man presented headache after a foot-race. Secondary
      visual deficit developed. On admission, bilateral cavernous sinus syndrome with
      bitemporal hemianopia was observed. The CT scan showed an enlarged sella eroded
      by an intrasellar soft tissue mass. Magnetic resonance imaging (MRI) confirmed
      the presence of the mass with peripheral enhancement following gadolinium
      injection. Decompression was carried out by transsphenoidal surgery. The
      microscopic study demonstrated infarction of the anterior hypophysis with
      peripheral tissular scarring. The post-operative outcome was characterized by
      visual recovery and anterior hypophyseal insufficiency. The possible
      pathophysiological mechanisms are discussed.

PMID- 8577359
TI  - [Frontal cerebral abscess, a rare complication of nasosinusal polyposis. Apropos
      of a case].
AB  - Sinusonasal polyposis is frequent but usually benign. A 77-year-old woman with an
      history of sinusonasal polyps, presented with fever and neurologic impairment.
      Radiologic imaging showed a polypoid mass filling the nose and sinuses, eroding
      the ethmoid bone, progressing intracranially, and causing brain abscess. The
      literature is reviewed, according to the relations between brain abscess
      development and nasal polyposis, with emphasis on intracranial extension of
      sinusonasal polyps. Treatment of the nasal polyps, usually based on the use of
      local or general corticosteroids, can avoid this serious complication.

PMID- 8577361
TI  - Blockade of glutamate receptors unmasks neuronal apoptosis after oxygen-glucose
      deprivation in vitro.
AB  - Mouse cortical cell cultures exposed to transient oxygen-glucose deprivation
      developed marked acute cell body swelling followed by neurodegeneration,
      consistent with necrosis-type death. This death was not attenuated by the protein
      synthesis inhibitor, cycloheximide, but was attenuated by addition of the N
      methyl-D-asparate antagonist, MK-801 (dizocilpine maleate), and the alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid/kainate antagonist, 6-cyano-7
      nitroquinoxaline-2,3-dione. If the deprivation insult was extended to overcome
      the protective effect of glutamate antagonists, neuronal death resulted that was
      associated with cell body shrinkage and DNA fragmentation, and was attenuated by
      cycloheximide. These data suggest that oxygen-glucose deprivation can induce in
      cortical neurons both excitotoxic necrosis, and apoptosis dependent on new
      macromolecule synthesis.

PMID- 8577362
TI  - Dantrolene inhibits long-term depression and depotentiation of synaptic
      transmission in the rat dentate gyrus.
AB  - The involvement of Ca release from intracellular stores in the induction of long
      term depression and depotentiation of excitatory synaptic transmission was
      investigated in the rat dentate gyrus using dantrolene, an agent known to block
      Ca release via the ryanodine receptor. In control slices, low-frequency
      stimulation (1 Hz for 15 min) induced robust long-term depression of baseline
      field excitatory postsynaptic potentials and depotentiation of previously
      established long-term potentiation. Dantrolene (50 microM) was found to block
      completely both long-term depression of baseline responses and depotentiation.
      Moreover, long-term potentiation induced by high-frequency stimulation was
      enhanced in the presence of dantrolene.

PMID- 8577363
TI  - The complementary nature of long-term depression and potentiation revealed by
      dual component excitatory postsynaptic potentials in hippocampal slices from
      young rats.
AB  - Homosynaptic long-term depression and long-term potentiation were studied in
      hippocampal slices from 12-18-day-old rats using field excitatory postsynaptic
      potentials recorded in the CA1 subfield (stratum radiatum). Independent estimates
      of the alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and the N
      methyl-D-aspartate receptor-mediated components of the field excitatory
      postsynaptic potential were obtained in parallel using early and late
      measurements of a dual component excitatory postsynaptic potential in a solution
      containing low (0.1 mM) magnesium and 1 microM of the AMPA receptor antagonist 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX). Long-term depression, induced by 2 Hz
      stimulation for 10 min, was observed as an equal relative depression of the AMPA
      and N-methyl-D-aspartate receptor-mediated components of the field excitatory
      postsynaptic potential, whereas long-term potentiation induced by single or
      repeated high-frequency stimulation, was seen initially as a predominant
      potentiation of the AMPA receptor-mediated component. Within the first 30-60 min,
      long-term potentiation gradually changed to more equal increases of the two
      components of the excitatory postsynaptic potential. During alternating induction
      of long-term depression and long-term potentiation, the AMPA and N-methyl-D
      aspartate receptor-mediated components could both be repeatedly regulated up and
      down. Long-term depression and long-term potentiation also showed several signs
      of interaction with each other during such experiments; e.g., long-term
      depression removed the occlusive effect of large long-term potentiation on a
      subsequent long-term potentiation, and long-term potentiation applied after the
      induction of long-term depression was found to be more stable than otherwise. The
      results support the notion that long-term depression and long-term potentiation
      employ changes in a common synaptic property. A tentative mechanism for this
      modification, expressed as equal changes of AMPA and N-methyl-D-aspartate
      receptor-mediated components of the excitatory postsynaptic potential, is an
      alteration in transmitter release, while the initial asymmetric part of long-term
      potentiation indicates involvement of an additional short-term modification.

PMID- 8577364
TI  - N-methyl-D-aspartate transmission modulates GABAB-mediated inhibition of rat
      hippocampal pyramidal neurons in vitro.
AB  - Slow inhibition was investigated by stimulating inhibitory neurons at the border
      of stratum radiatum and lacunosum-moleculare with focal microapplications of
      glutamate, while recording resultant slow inhibitory postsynaptic potentials in
      CA1 pyramidal neurons in rat hippocampal slices. The slow inhibitory postsynaptic
      potentials evoked had an average peak amplitude of -2.2 mV, measured at -60 mV.
      Their peak conductance was 2.5 nS. These events were characterized as slow GABAB
      inhibitory postsynaptic potentials because they reversed at -90 mV, and were
      blocked by CGP 35348 (500 microM). Exposure to magnesium-free solutions augmented
      glutamate-evoked slow inhibitory postsynaptic potentials. Mean peak amplitude and
      conductance were -3.1 mV and 4.0 nS. Exposure to the N-methyl-D-aspartate
      antagonist MK-801 (20 microM) allowed separation of the glutamate-triggered slow
      inhibitory postsynaptic potential into components induced by non-N-methyl-D
      aspartate and N-methyl-D-aspartate receptor activation. The N-methyl-D-aspartate
      component dominated, even under control conditions, and could account for up to
      60% of the control slow inhibitory postsynaptic potential. Thus, the activation
      and recruitment of GABAB-mediated inhibition depend on both non-N-methyl-D
      aspartate and N-methyl-D-aspartate-mediated excitation of inhibitory
      interneurons. Under physiological conditions slow inhibition may act as an
      important synaptic filtering mechanism, but when N-methyl-D-aspartate-mediated
      excitation increases, slow inhibition is further recruited, providing an
      important means to offset excessive excitation.

PMID- 8577365
TI  - Differential neuronal vulnerability to amino-oxyacetate and quinolinate in the
      rat parahippocampal region.
AB  - Injection of the "indirect" excitotoxin amino-oxyacetate into the entorhinal area
      causes acute behavioral seizures and preferential neuronal loss in layer III of
      the medial entorhinal cortex in rats. We examined here whether the effects of
      amino-oxyacetate could be duplicated by local injections of the endogenous N
      methyl-D-aspartate receptor agonist and direct excitotoxin, quinolinate. Amino
      oxyacetate (685 nmol) or quinolinate (30, 45 or 60 nmol) were injected into the
      entorhinal cortex of rats anesthetized with choral hydrate (360 mg/kg). Separate
      groups of animals were co-treated with the N-methyl-D-aspartate receptor
      antagonist dizocilpine maleate (2 mg/kg) or given a higher dose of chloral
      hydrate (500 mg/kg). Rats that received amino-oxyacetate and a low anesthetic
      dose consistently displayed acute behavioral seizures and showed preferential
      loss of neurons in layer III of the medial entorhinal cortex. Animals that were
      given quinolinate did not display behavioral seizures, and showed preferential
      degeneration of neurons in layer V of the entorhinal cortex. Moreover,
      quinolinate-injected rats frequently exhibited neuronal loss in the superficial
      layers of the dorsal perirhinal cortex. The behavioral and neuropathological
      sequelae of amino-oxyacetate, but not quinolinate-induced neurotoxicity, were
      abolished by prolonged chloral hydrate anesthesia. In spite of these apparent
      qualitative differences between the two toxins, neurodegeneration induced by
      either amino-oxyacetate or quinolinate was completely prevented by dizocilpine
      maleate. These data suggest that a heterogeneous distribution of
      pharmacologically distinct N-methyl-D-aspartate receptor subtypes in the
      parahippocampal region may underlie the distinct neurodegenerative properties of
      the two toxins. Since the lesion caused by amino-oxyacetate bears remarkable
      similarities to neuropathological changes which have been described in this
      structure in temporal lobe epilepsy, further elucidation of the mechanisms of
      cellular toxicity of amino-oxyacetate may hold clues for the pathogenesis of this
      disease.

PMID- 8577366
TI  - Periodically modulated inhibition and its postsynaptic consequences--I. General
      features. Influence of modulation frequency.
AB  - Our aim was to examine the relation, or "synaptic coding", between spike trains
      across a synapse with inhibitory postsynaptic potentials when the presynaptic
      rate is modulated periodically and the postsynaptic cell is a pacemaker.
      Experiments were on the synapse in crayfish stretch receptor organs. Spike trains
      were considered point processes along time; the time series of corresponding pre-
      and postsynaptic intervals were extracted. Analyses used displays of intervals
      along time and order ("basic graphs", and "rasters", respectively), displays of
      differences between intervals along order ("recurrence plots"), cycle histograms
      (as such and as Lissajous diagrams with presynaptic and postsynaptic on the
      abscissae and ordinate, respectively), and correlation histograms. Cycle
      histograms and correlation histograms demonstrated that all presynaptic
      modulation frequencies (1/60-10 Hz) are reflected postsynaptically; novel
      frequencies may arise, not always relating simply to the pre- or postsynaptic
      ones. The transferred frequency domain is broad and physiologically meaningful.
      Indeed, vitally important functions have strong periodicities in all portions of
      the explored domain, and so do the discharges of participating neurons. Overall,
      pre- and postsynaptic discharges change oppositely, one accelerating while the
      other slows. Locally, however, pre- and postsynaptic discharges contrast clearly
      in other ways. The presynaptic evolution is everywhere smooth and orderly, half
      cycles usually are symmetric, and there is a single kind of discharge, as
      expected because the presynaptic axon follows well the controlling stimuli. The
      postsynaptic cycle shows marked local distortions. These involve presynaptic
      domains called "congruent portions" where changes are in the same sense (e.g.,
      joint accelerations), "saturated" domains where postsynaptic discharges are
      arrested, and asymmetric sensitivities to presynaptic change with hysteretic
      loops in the Lissajous diagrams; the postsynaptic discharge is heterogeneous
      showing dissimilar forms in succession. Congruent portions are either "positive
      segments" with pre- to postsynaptic rate ratios practically 1:1, 2:1, 1:1, or
      parts of Lissajous loops. Different modulation frequencies have different
      postsynaptic consequences. Differences involve the width and number of positive
      segments, the proportion of the cycle with saturation, the sense, magnitude and
      lead-lag characteristics of the hysteretic loops, etc. Because their consequences
      are separable, frequencies are classified within categories labelled "low" (under
      0.5 Hz), "high" (between 0.5 and 5.0 Hz) and "very high" (over 5.0 Hz).
      Categories arise widely but each prevails in different biological functions
      (e.g., low or high in, respectively, respiration or vibratory sensitivity). The
      refactoriness of the inhibitory fibre affects how it can be modulated:
      consequently, the very high category resembles pacemaker discharges and was not
      analysed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8577367
TI  - Periodically modulated inhibition and its postsynaptic consequences--II.
      Influence of modulation slope, depth, range, noise and of postsynaptic natural
      discharges.
AB  - This paper examines the relation, or "synaptic coding", between the discharges of
      inhibitory fibres whose instantaneous firing rate is modulated periodically and
      pacemaker postsynaptic neurons using crayfish synapses and point process
      statistics. Several control parameters were varied individually, and the other
      maintained constant as far as possible: it extends the preceding publication that
      described the general features and varied only the modulation frequency [Segundo
      et al. (1995) Neuroscience 68, 657-692]. Statistics were mainly cycle histograms
      and Lissajous diagrams (with presynaptic and post-synaptic histograms on the
      abscissae and ordinate, respectively), complemented occasionally by displays of
      intervals along time and of interval differences along order ("basic graphs" and
      "recurrence plots", respectively). The postsynaptic influence of modulated
      inhibitory discharges is characteristically sensitive to all control parameters
      examined. (1) The frequency was reported in the companion paper [Segundo et al.
      (1995) Neuroscience 68, 657-692]. (2) The average slope per half-cycle,
      controlled via either frequency or depth, acts by way of its magnitude and sign
      in ways revealed by hysteretic loops. Hysteresis increases and varies as the
      modulation's steepness increases: it is minor and with a single clockwise loop at
      small slopes, but major and multi-looped at the larger ones. Slopes, because of
      their different postsynaptic consequences, were separated into the categories of
      "steep", "gentle" and "abrupt" if around, respectively, 1.0, 30.0 and 150.0 s-2.
      The influence of slopes in restricted portions of the cycle depends on their
      position on the inhibitory rate scale. (3) The modulation's range acts by way of
      its depth and of its position on the inhibitory rate scale. Deeper ranges, when
      compared with the shallower ones they contain, induce effects similar to those of
      shallower modulations with their central portion, plus effects peculiar to them
      at extreme rates. Changes in range position from the centre to the extremes of
      the inhibitory rate scale are influential (e.g., saturations appear). Changes
      within the centre can be highly influential, particularly when ranges are narrow
      and close to the postsynaptic natural rate, and modulation frequencies are low:
      relations between corresponding rates can be linear increasing, linear decreasing
      or piecewise linear. Changes around extreme rates are negligible, however, and
      saturations are present. (4) The usual modulations whose individual cycles did
      not differ from the cycle histogram were compared to others with the same cycle
      histograms but whose individual cycles had an unpredictable fast variability
      referred to as "noise".(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8577368
TI  - Adenosine antagonists potentiate D2 dopamine-dependent activation of Fos in the
      striatopallidal pathway.
AB  - Adenosine antagonists potentiate dopamine-mediated behaviours. A2a adenosine and
      D2 dopamine receptors are abundantly co-expressed within the striatopallidal
      subset of striatal neurons, suggesting that this is the site of interaction
      between A2a and D2 receptors. We show that the D2-dependent induction of the
      immediate early gene c-Fos occurs in striatopallidal neurons 3 h following
      injection of reserpine (10 mg/kg). We used this paradigm to test whether
      adenosine antagonists modulate D2-dependent activation of striatopallidal
      neurons. The non-selective A1-A2 adenosine antagonists theophylline (25 mg/kg) or
      3,7-dimethyl-1-propargylxanthine (25 mg/kg) potentiated the effect of a
      submaximal dose of the D2 dopamine agonist quinpirole (0.05 mg/kg) to prevent the
      induction of striatal c-Fos following reserpine. Co-administration of the A2a
      receptor antagonist 8-(3-chlorostyryl) caffeine (5 mg/kg) with quinpirole (0.05
      mg/kg) also attenuated striatal c-Fos induction following reserpine to a greater
      extent than 0.05 mg/kg quinpirole alone. When administered prior to reserpine,
      theophylline (25 mg/kg) or 3,7-dimethyl-1-propargylxanthine (25 mg/kg) partially
      attenuate the induction of striatal c-fos. These results demonstrate that
      systemic administration of adenosine antagonists enhance D2 dopamine receptor
      dependent regulation of c-Fos in the striatopallidal pathway. These results
      support a functional interaction between A2a adenosine and D2 dopamine receptors
      in striatopallidal neurons.

PMID- 8577369
TI  - Reduction of dopamine D2 receptor transduction by activation of adenosine A2a
      receptors in stably A2a/D2 (long-form) receptor co-transfected mouse fibroblast
      cell lines: studies on intracellular calcium levels.
AB  - A stably co-transfected mouse fibroblast cell line, which expresses the long form
      of the human dopamine D2 receptor and the dog adenosine A2a receptor, was used to
      analyse the mechanism underlying changes in the cytosolic free calcium
      concentration ([Ca2+]i) induced by activation of D2 (long-form) receptors and its
      modulation by the A2a receptor agonist CGS 21680 by means of fura-2 imaging.
      Quinpirole (1-1000 nM), a D2 receptor agonist, caused a concentration-dependent
      increase in [Ca2+]i. Haloperidol, a preferential D2 receptor antagonist,
      completely blocked this [Ca2+]i response to quinpirole. Preincubation with Ca(2+)
      free medium containing 2 mM EGTA or a medium containing 320 mM ethanol, an
      inositol 1,4,5-triphosphate receptor antagonist, substantially diminished the
      increase in [Ca2+]i evoked by quinpirole. Furthermore, quinpirole totally failed
      to elevate [Ca2+]i in a medium containing both 2 mM EGTA and 320 mM ethanol. CGS
      21680 (1-500 nM) did not, by itself, exert any significant effect on [Ca2+]i.
      However, 100 nM of CGS 21680 substantially counteracted the [Ca2+]i responses to
      quinpirole (10-1000 nM). Moreover, this counteraction still occurred after
      blocking Ca2+ mobilization from intracellular stores with ethanol, but
      disappeared when the cells were pretreated with the Ca(2+)-free medium containing
      2 mM EGTA. Our findings imply that the D2 (long-form) receptors in the present
      fibroblast cell line can raise [Ca2+]i both via Ca2+ influx from the
      extracellular medium and Ca2+ release from intracellular stores via activation of
      inositol 1,4,5-triphosphate receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8577370
TI  - Intrathalamic striatal grafts survive and affect circling behaviour in adult rats
      with excitotoxically lesioned striatum.
AB  - Current models of basal ganglia disorders suggest that choreoathetosis is the end
      result of reduced GABAergic inhibition of the motor thalamus. Graft-derived
      release of GABA from intrastriatal striatal grafts has also been reported. In the
      present work, cell suspension grafts from embryonic day 14-15 rat striatal
      primordia were implanted close to the ventromedial thalamic nucleus to
      investigate whether they can develop and survive in this ectopic location, and
      whether they induce changes in the circling behaviour of the host. The grafts
      were implanted either in normal rats or in rats whose striatum had been lesioned
      with ibotenic acid. These grafts were implanted either ipsilateral or
      contralateral to the lesioned striatum. Additionally, some rats received
      intrastriatal grafts, and lesioned but non-grafted rats and lesioned rats that
      had received injections of saline or of cell suspensions from fetal spinal cord
      in the thalamus were used as control. Four to eight months after transplantation,
      circling behaviour after amphetamine or apomorphine injection was evaluated.
      Serial sections were stained with Cresyl Violet and studied immunohistochemically
      with antibodies against DARPP-32 (dopamine- and adenosine 3',5'-monophosphate
      regulated phosphoprotein, as striatal marker), Fos protein, glutamate
      decarboxylase (67,000 mol. wt), glutamate decarboxylase (65,000 mol. wt) and
      GABA. Cresyl Violet sections showed that the intrathalamic striatal grafts
      developed into tissue masses resembling those observed in intrastriatal striatal
      grafts. DARPP-32 immunohistochemistry revealed that the grafts were composed of
      DARPP-32 immunoreactive (striatum-like) and DARPP-32-negative patches. The
      intrathalamic grafts of rats which had received a low dose of apomorphine (0.25
      mg/kg) 2 h before perfusion showed clusters of intensely Fos-immunoreactive
      nuclei throughout the transplant, indicating that these cells had developed
      dopamine receptors and supersensitivity to dopamine agonists. Double Fos and
      DARPP-32 immunohistochemistry revealed that the Fos-positive nuclei were located
      in the striatum-like areas. Finally, the intrathalamic grafts also contained
      neurons immunoreactive to GABA and glutamate decarboxylase (65,000 and 67,000
      mol. wt). Rats that had received intrathalamic grafts contralateral to the
      lesioned striatum (i.e. contralateral to the lesion-induced turning direction)
      showed a significant reduction of circling both after amphetamine (78% reduction)
      or apomorphine (77% reduction) injection. Rats that had received grafts
      ipsilateral to the lesioned striatum showed a 75% decrease in amphetamine-induced
      circling, but no significant change in apomorphine-induced circling. No
      significant drug-induced circling was observed in non-lesioned and grafted rats.
      Sham grafting (saline) or grafting of weakly GABAergic tissue (fetal spinal cord)
      had no significant effects on lesion-induced circling behaviour.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8577371
TI  - The development of striatal patch/matrix organization after prenatal
      methylazoxymethanol: a combined immunocytochemical and bromo-deoxy-uridine
      birthdating study.
AB  - The antimitotic drug methylazoxymethanol was used to destroy striatal patch
      neurons during their three-day-period of neurogenesis in the rat. Single or
      multiple injections of methylazoxymethanol were given during embryonic days 13
      15, the period when patch neurons are known to undergo their final cell division.
      Methylazoxymethanol treatments produced a dramatic reduction in striatal volume.
      Immunocytochemical analysis revealed the continued presence of patches of neurons
      that were substance P-immunoreactive and devoid of calbindin and enkephalin
      immunoreactivity. Both the number of patches and relative volume occupied by
      patches was reduced in methylazoxymethanol-treated striata. Patch neurons could
      also be labelled by an intrastriatal injection of FluoroGold during the first
      postnatal week. The early ingrowth of nigrostriatal dopamine afferents was less
      noticeably patchy in the methylazoxymethanol-treated animals, in part owing to an
      overall increase in density. Large reductions in the number of neurons
      immunoreactive for choline acetyltransferase were observed, whereas NADPH
      diaphorase-stained neurons were not reduced unless methylazoxymethanol was given
      on embryonic day 15. Injections of bromo-deoxy-uridine, either during or after
      the 24 h that each methylazoxymethanol injection was considered to be effective,
      revealed that (i) some patch neurons continued to be generated in the 24-h period
      following methylazoxymethanol administration, and (ii) many patch neurons were
      generated after the effects of methylazoxymethanol had worn off. These findings
      demonstrate that it was impossible to completely eliminate the patches using
      methylazoxymethanol injections during the period of patch neurogenesis. However,
      methylazoxymethanol treatment during this time did produce a dramatic loss of
      cells and a relatively greater reduction in patch volume. Despite this
      disruption, the appropriate compartmentalization of neuroactive substances
      appeared to be maintained.

PMID- 8577372
TI  - Changes in hypothalamic cholecystokininA and cholecystokininB receptor subtypes
      and associated neuropeptide expression in response to salt-stress in the rat and
      mouse.
AB  - This study demonstrates cholecystokinin receptor plasticity in response to salt
      loading in the rat and mouse hypothalamus. It identifies, for the first time, the
      cholecystokinin receptor subtypes involved, firstly by receptor autoradiography
      and secondly by in situ hybridization. Both species showed increases in
      hypothalamic [125I]Bolton Hunter-cholecystokinin-8 binding. Co-incubation with
      the specific cholecystokininA and cholecystokininB antagonists, devazepide and CI
      988, indicated that in the rat cholecystokininB receptor binding markedly
      increased, with a small increase in cholecystokininA receptor binding. In the
      mouse the response was comprised solely of cholecystokininA receptors. In situ
      hybridization studies were carried out on a range of peptide messenger
      ribonucleic acids after salt-loading. In the rat large increases in hypothalamic
      gene expression were detected for oxytocin, vasopressin, corticotrophin-releasing
      factor and preprocholecystokinin. In the mouse only vasopressin messenger
      ribonucleic acid increased, whilst hypothalamic oxytocin, preprocholecystokinin
      and corticotropin-releasing factor remained unchanged. However, corticotrophin
      releasing factor messenger ribonucleic acid increased in the mouse amygdala. In
      situ hybridization was performed using oligonucleotide probes specific for either
      the cholecystokininA or cholecystokininB receptor messenger ribonucleic acid, and
      this showed good agreement with the receptor autoradiography. CholecystokininB
      receptor expression was upregulated in the rat hypothalamus along with a small
      but significant increase in cholecystokininA receptors. In the mouse only
      cholecystokininA receptor expression was increased. In addition to these
      molecular changes rats lost about 25% of their body weight during six days of
      salt-challenge, whilst mice continued to grow in line with controls. This work
      demonstrates differential changes in cholecystokinin receptor subtype binding
      between the rat and the mouse. It represents the first report of differential
      changes in cholecystokininA and cholecystokininB receptor messenger ribonucleic
      acids within the brain, and shows that cholecystokinin receptors within the
      rodent hypothalamus are capable of plastic responses to chronic osmotic stress.

PMID- 8577373
TI  - -Fos expression in female hamster brain following sexual and aggressive
      behaviors.
AB  - The goal of these experiments was to use c-Fos immunocytochemistry to determine
      areas of the female hamster brain that are active during lordosis and aggression.
      Ovariectomized hamsters were given (i) estradiol and progesterone, plus a
      lordosis test, (ii) estradiol and progesterone, but no lordosis test, (iii) oil,
      plus an aggressive behavior test, or (iv) oil, but no behavior test. Results
      showed that following lordosis, there was increased c-Fos expression in the
      medial bed nucleus of the stria terminalis, medial accumbens, medial preoptic
      nucleus, paraventricular nucleus and medial amygdala. Following a single
      aggression test, c-Fos was significantly increased only within the medial
      amygdala. There was no effect of lordosis or aggression on c-Fos expression
      within the lateral or central ventromedial hypothalamus, suprachiasmatic nucleus
      or dorsal midbrain central gray. In a second experiment, ovariectomized female
      hamsters were given (i) repeated aggressive experience, (ii) a single aggression
      test or (iii) no aggression test. Because some females were not aggressive
      towards males, they became a separate group post hoc. The number of cells
      expressing c-Fos was higher in the medial preoptic nucleus and medial amygdala of
      females given a single aggressive test and in non-aggressive females vs control
      females. Females given prior aggressive experience showed higher c-Fos expression
      only in the medial preoptic nucleus. These results demonstrate that increased
      neural activation in several forebrain nuclei is seen after sexual or aggressive
      behaviors in female hamsters. However, because the pattern of c-Fos staining in
      the non-aggressive females was similar to the pattern in aggressive females, this
      questions previous conclusions regarding the behavioral specificity of these
      effects and suggests instead that such activation is common to social
      interactions in general.

PMID- 8577374
TI  - Functional recovery of forelimb response capacity after forelimb primary motor
      cortex damage in the rat is due to the reorganization of adjacent areas of
      cortex.
AB  - Functional recovery after brain damage has been described frequently and
      different mechanisms have been proposed to account for the observed recovery. One
      possible mechanism involves the capacity of one part of the brain to take over
      the function of another. A possible area for this to take place is in the
      cerebral cortex, where a variety of reorganizational processes have been
      described after different manipulations. We show in the present study that the
      forelimb force and response capacity of the rat, which becomes highly impaired
      after the bilateral ablation of the forelimb primary motor cortex, is recovered
      when the animals receive an electrical stimulation in the ventral tegmental
      nucleus contingent to each forelimb response in the task. Microstimulation
      mapping of the cortical areas adjacent to the forelimb primary motor cortex
      revealed the appearance of an area located caudolaterally to the forelimb primary
      motor cortex, where forelimb movements could be evoked in recovered animals but
      to a lesser extent in non-recovered animals. A positive and significant
      correlation was observed between the size of the reorganized forelimb area and
      the behavioral performance of the animals. Ablation of the forelimb reorganized
      area in recovered animals reinstated the forelimb behavioral impairment, while
      the same lesion in normal animals had no effect on the behavioral performance.
      The results indicate that recovery after bilateral forelimb primary motor cortex
      ablation may be due to the organization of specific adjacent areas in the cortex.

PMID- 8577375
TI  - Magnesium ions reduce motoneuron death following nerve injury or exposure to N
      methyl-D-aspartate in the developing rat.
AB  - Developing motoneurons can be induced to die by target deprivation and there is
      evidence that this cell death involves the excitotoxic effects of N-methyl-D
      aspartate. Treatment with dizocilpine maleate, an antagonist of this receptor,
      has been shown to rescue a proportion of those motoneurons destined to die
      following nerve injury at birth. However, this is a relatively toxic compound. In
      this study we examined whether systemic treatment with magnesium sulphate, a non
      competitive antagonist of the N-methyl-D-aspartate receptor which is better
      tolerated than dizocilpine maleate, could prevent motoneuron death. Motoneurons
      were induced to die either by sciatic nerve injury at birth or by nerve injury at
      five days followed by exposure to N-methyl-D-aspartate. The number of surviving
      motoneurons reinnervating the tibialis anterior and extensor digitorum longus
      muscles were counted using retrograde labelling. Following nerve injury at birth
      and treatment with magnesium sulphate, there was a small increase in the survival
      of injured motoneurons, although this improvement was not significant. Nerve
      injury at five days does not result in motoneuron death, but when followed by
      treatment with N-methyl-D-aspartate, only 42 +/- 2.9% of motoneurons to these
      flexor muscles survived. Treatment with magnesium sulphate prior to injection of
      N-methyl-D-aspartate significantly increased motoneuron survival, so that 67 +/-
      5.8% of motoneurons survived. Thus, systemic treatment with magnesium can prevent
      the death of motoneurons rendered susceptible to the excitotoxic effects of N
      methyl-D-aspartate by nerve injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8577376
TI  - Succinate dehydrogenase activity and soma size of motoneurons innervating
      different portions of the rat tibialis anterior.
AB  - The spatial distribution, soma size and oxidative enzyme activity of gamma and
      alpha motoneurons innervating muscle fibres in the deep (away from the surface of
      the muscle) and superficial (close to the surface of the muscle) portions of the
      tibialis anterior in normal rats were determined. The deep portion had a higher
      percentage of high oxidative fibres than the superficial portion of the muscle.
      Motoneurons were labelled by retrograde neuronal transport of fluorescent
      tracers: Fast Blue and Nuclear Yellow were injected into the deep portion and
      Nuclear Yellow into the superficial portion of the muscle. Therefore, motoneurons
      innervating the deep portion were identified by both a blue fluorescent cytoplasm
      and a golden-yellow fluorescent nucleus, while motoneurons innervating the
      superficial portion were identified by only a golden-yellow fluorescent nucleus.
      After staining for succinate dehydrogenase activity on the same section used for
      the identification of the motoneurons, soma size and succinate dehydrogenase
      activity of the motoneurons were measured. The gamma and alpha motoneurons
      innervating both the deep and superficial portions were located primarily at L4
      and were intermingled within the same region of the dorsolateral portion of the
      ventral horn in the spinal cord. Mean soma size was similar for either gamma or
      alpha motoneurons in the two portions of the muscle. The alpha motoneurons
      innervating the superficial portion had a lower mean succinate dehydrogenase
      activity than those innervating the deep portion of the muscle. An inverse
      relationship between soma size and succinate dehydrogenase activity of alpha, but
      not gamma, motoneurons innervating both the deep and superficial portions was
      observed. Based on three-dimensional reconstructions within the spinal cord,
      there were no apparent differences in the spatial distribution of the
      motoneurons, either gamma or alpha, associated with the deep and superficial
      compartments of the muscle. The data provide evidence for an interdependence in
      the oxidative capacity between a motoneuron and its target muscle fibres in two
      subpopulations of motoneurons from the same motor pool, i.e. the same muscle.

PMID- 8577377
TI  - Reactive neurogenesis during regeneration of the lesioned medial cerebral cortex
      of lizards.
AB  - This study reports that lesion of the adult lizard medial cortex (lizard
      hippocampal fascia dentata) induces a short period of intensive neurogenesis
      which we have termed reactive neurogenesis; a cell proliferation event that
      occurs in the subjacent ependyma. Specific lesion of the medial cortex was
      achieved by intraperitoneal injection of the neurotoxin 3-acetylpyridine and
      proliferating cells were detected using tritiated thymidine or 5
      bromodeoxiuridine pulse labelling. After lesion, granule neurons in the lizard
      medial cortex cell layer appeared pyknotic and died; they were then removed and
      progressively replaced by a set of new neurons. These neurons were mostly
      generated from the second to the seventh day post-lesion. A dramatic temporal
      increment of labelled ependymal cells was detected when either tritiated
      thymidine or 5-bromodeoxiuridine pulses were delivered in that period. The
      maximum of about five thousand labelled cells per hemisphere was reached by the
      fourth day after the lesion. Beyond the seventh day post-lesion, the numbers of
      labelled cells returned to a level of about four hundred per hemisphere, similar
      to that of the control specimens. Electron microscopy revealed that the recently
      generated cells were neuroblasts or immature neurons with a characteristic
      pattern of chromatin condensation and a high number of ribonucleic granules.

PMID- 8577378
TI  - An ultrastructural study of cholinergic and non-cholinergic neurons in the
      laterodorsal and pedunculopontine tegmental nuclei in the rat.
AB  - Synaptic connectivity and other ultrastructural features of cholinergic and non
      cholinergic neurons in the laterodorsal and pedunculopontine tegmental nuclei
      were investigated with electron microscopy combined with pre-embedding
      immunohistochemistry for choline acetyltransferase. Quantitative morphometric
      analyses were conducted on selected immunopositive as well as immunonegative
      neurons. The ultrastructure of immunoreactive neurons in the laterodorsal and
      pedunculopontine tegmental nuclei was similar. In both nuclei, immunoreactive
      neurons were among the larger neurons, and somatic areas of immunopositive
      neurons in single thin sections were larger than those of immunonegative neurons
      by an average of 40%. Immunopositive somata varied in shape, appearing polygonal,
      fusiform or oval. Regardless of immunoreactivity, however, neurons in the
      pedunculopontine nucleus tended to have more irregular shapes than those in the
      laterodorsal tegmental nucleus. Immunoreactive neurons in both the nuclei had
      abundant cytoplasmic organelles and a large, clear nucleus with a few infoldings.
      Usually, about a quarter of the surface of an immunopositive soma was covered
      with astrocytic processes, and some immunopositive somata were directly apposed
      to an astrocyte. Immunoreactive dendrites and, less frequently, axon terminals
      were seen in close apposition to endothelial cells of blood capillaries or
      pericytes. Immunoreactive somata and dendrites in the laterodorsal and
      pedunculopontine tegmental nuclei received many synapses, mainly from unlabelled
      axon terminals. The mean number (4.7 +/- 1.8) of synapses received by
      immunolabelled somata in single thin sections was greater, by about 70%, than
      those received by unlabelled somata. The presynaptic axon terminals synapsing
      with immunoreactive somata commonly contained small, round and clear vesicles,
      and 20% of them contained a few dense-cored vesicles as well. Immunoreactive
      dendrites, in addition, received synapses from unlabelled axon terminals
      containing flat and clear vesicles, which accounted for 15% of the synapses with
      immunoreactive dendrites. Many immunopositive axon terminals were present in both
      the tegmental nuclei. They contained clear round vesicles, and usually synapsed
      with unlabelled dendrites. A few immunolabelled axons, however, appeared to
      synapse with immunopositive somata and dendrites. Immunoreactive fibres were also
      present in both the tegmental nuclei. They were either thinly myelinated or
      unmyelinated. In conclusion, the ultrastructural morphology of cholinergic
      neurons in the laterodorsal and pedunculopontine tegmental nuclei is similar, and
      these neurons represent a distinct population of neurons in both nuclei in that
      they are larger and receive more synaptic contacts than non-cholinergic neurons.
      Cholinergic neurons, however, appear to receive synapses from cholinergic axon
      terminals only rarely, despite the abundance of cholinergic terminals in the
      tegmental nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8577379
TI  - Tachykinins alter inositol phosphate formation, but not cyclic AMP levels, in
      primary cultures of neonatal rat spinal neurons through activation of neurokinin
      receptors.
AB  - The naturally occurring tachykinins, substance P, neurokinin A and neurokinin B,
      induce the formation of inositol phosphates or cAMP in a variety of tissues but
      their effects on neurons have not been resolved. We used primary cultures of
      neonatal rat spinal cord to determine whether neurokinin receptors mediate
      changes in these second messengers in spinal neurons. We found that substance P,
      neurokinin A and neurokinin B induced the formation of inositol phosphates in a
      concentration-dependent manner with similar potencies (EC50S: 3.6, 5.7 and 21.3
      nM, respectively), but at concentrations tested (0.1-1.0 microM) these peptides
      had no effect on cAMP levels. All three tachykinins induced the formation of
      inositol phosphates predominately by activation of neurokinin1 receptors. CP
      96,345 and WIN 51,708, neurokinin1 receptor antagonists, attenuated the response
      to substance P, neurokinin A and neurokinin B. GR 103,537, a neurokinin2 receptor
      antagonist, had no effect on the responses induced by any of the tachykinins.
      Furthermore, the selective neurokinin1 receptor agonist, GR-73632, induced the
      formation of inositol phosphates in a concentration-dependent manner, whereas the
      selective neurokinin2 receptor agonist, GR-64349, generated inositol phosphates
      only at the highest concentration tested (10 microM). Senktide, a neurokinin3
      receptor agonist, did not induce the formation of inositol phosphates at any of
      the concentrations tested (0.01-10 microM). Inositol phosphate formation appeared
      to be due to a direct effect of the tachykinins on neuronal neurokinin1
      receptors. These results suggest that biological responses in spinal neurons
      following activation of neurokinin1 receptors are mediated mainly by the
      hydrolysis of phosphoinositol 4,5-bisphosphate to form inositol 1,4,5
      trisphosphate and diacylglycerol. It remains to be determined which of these
      second messengers mediates the increased neuronal excitability and depolarization
      that occurs in response to substance P.

PMID- 8577380
TI  - Quantitative autoradiographic localization of [125I-Tyr8]bradykinin receptor
      binding sites in the rat spinal cord: effects of neonatal capsaicin,
      noradrenergic deafferentation, dorsal rhizotomy and peripheral axotomy.
AB  - In vitro receptor autoradiography was used to localize, quantify and characterize
      [125I-Tyr8]bradykinin binding sites in all major spinal cord segments of normal
      rats and animals subjected to various chemical treatments and surgical lesions.
      [125I-Tyr8]bradykinin specific binding sites were predominantly located to
      superficial laminae of the rat dorsal horn, with the substantia gelatinosa
      showing the highest density of labelling (values ranging from 3.1 fmol/mg tissue
      in cervical to 4.5 fmol/mg tissue in lumbar segments). A moderate density (1.8
      3.0 fmol/mg tissue) of specific binding was observed in lamina III, whereas in
      other areas, i.e. laminae I and IV-X, lower amounts of labelling were detected.
      Within the superficial laminae of the dorsal horn, [125I-Tyr8]bradykinin binding
      was largely distributed over the neurophil with some perikarya showing
      concentrations of labelling. In contrast, the ventral horn showed a rather
      homogeneous distribution of [125I-Tyr8]bradykinin binding over the neuropil, with
      silver grain alignments surrounding motoneuron perikaryas and proximal processes.
      Bradykinin, [Tyr8]bradykinin and B2 receptor antagonists (D-Arg[Hyp3,Thi5,D
      Tic7,Oic8]bradykinin (Hoe 140), D-Arg[Tyr3,D-Phe7,Leu8]bradykinin, D-Arg[Hyp3,
      Leu8]bradykinin, D-Arg[Hyp2, Thi5,8,-Phe7]bradykinin D-Arg[Hyp3, D-Phe7,
      Leu8]bradykinin, Tyr0, D-Arg[Hyp3, D-Phe7, Leu8]bradykinin inhibited [125I-Tyr8]
      bradykinin binding with very high subnanomolar affinities, while the B1 receptor
      agonist (Tyr0,des-Arg10-kallidin) and antagonist ([Leu8]-des-Arg9-bradykinin) did
      not significantly affect [125I-Tyr8]bradykinin binding at up to micromolar
      concentrations. Two weeks after unilateral lumbar dorsal rhizotomy (L1-L6) or
      peripheral lesions of the sciatic nerve, significant decreases ( +/- 50%) in
      [125I-Tyr8]bradykinin binding sites were found in ipsilateral laminae I-III of
      lumbar spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8577381
TI  - Differential distribution of calbindin-D28k and parvalbumin in somatic and
      visceral sensory neurons.
AB  - The purpose of the present investigation was to determine whether calbindin-D28k
      and parvalbumin are distributed to different subpopulations of somatic and
      visceral sensory neurons. Immunofluorescent and retrograde techniques were
      combined to examine the distribution of calbindin- and parvalbumin-like
      immunoreactivity in the cell bodies of somatic and visceral primary afferent
      neurons in dorsal root ganglia L1-S1 of rats. Calbindin and parvalbumin were
      differentially distributed to essentially non-overlapping subpopulations of
      primary sensory neurons that could be distinguished by their segmental and size
      distributions, as well as by their innervation of somatic and visceral
      structures. Calbindin-like immunoreactivity was found in a population of smaller
      sized cell bodies comprising approximately 14%of all dorsal root ganglion cells
      examined, with the proportions being greatest in L6 and S1. In contrast,
      parvalbumin was found in a population of larger-sized cells that made up about
      11% of dorsal root ganglion cells and that were most concentrated in L4 and L5.
      Sensory neurons were further characterized by retrograde transport following the
      application of the neuroanatomical tracer FluoroGold to somatic (sural and
      gastrocnemius) and visceral (hypogastric and pelvic) nerves. Somatic tissues were
      innervated by a population of calbindin-containing as well as a separate
      population of parvalbumin-containing sensory neurons. In contrast, afferent
      neurons innervating visceral structures contained only a subpopulation of
      calbindin-containing neurons and very few parvalbumin-positive cells.

PMID- 8577382
TI  - The pupillary light response: functional and anatomical interaction among inputs
      to the pretectum from transplanted retinae and host eyes.
AB  - Pupilloconstriction to light can be mediated in rats through direct illumination
      of retinae previously transplanted to intracranial locations. Transplant-driven
      and normal pupillary light responses are stable under optimal testing conditions,
      and parameters describing the response can be quantified precisely. The present
      study demonstrates the interaction between transplant-driven and normal pupillary
      response patterns. When stimuli are presented concurrently to a transplanted
      retina and to the remaining eye in host rats, a greater degree of
      pupilloconstriction occurs than when either the transplanted or the host eye is
      illuminated independently. This suggests that transplant and host retinal inputs
      act in concert to determine pupil diameter. The second portion of this study
      investigates the pattern of retinal input to the pretectum to determine if a
      structural basis for such functional interactions may exist. Crossed and
      uncrossed retinal projections to the olivary pretectal nucleus occupy non
      overlapping regions of this bilaterally represented nucleus in normal rats, with
      a greater number of optic axons directed to the contralateral olivary pretectal
      nucleus. Retinae transplanted to the midbrain of neonatal rats, from whom the
      contralateral eye had been removed, also project to the olivary pretectal nucleus
      at maturity. By contrast with the normal pattern of segregated retinal inputs,
      however, the terminal fields of transplant axons were found to overlap
      extensively with the retinal projection from the remaining host eye. In addition,
      the relative proportion of transplant axons directed to the ipsilateral and
      contralateral olivary pretectal nucleus varied among animals. The lack of spatial
      segregation between inputs from transplant and host sources and the relative
      proportion of ipsilateral and contralateral transplant axons together may
      represent a structural basis for the observed functional interactoin of these
      inputs to the neural circuit subserving pupilloconstriction to light. These
      features may also relate to the marked improvements in transplant-mediated
      responses that frequently occur when optic input from the remaining host eye is
      eliminated. The results presented here, together with our previous transplant
      studies, show that this preparation can be used to provide insight into more
      general questions as to the dynamic interactions that occur between converging
      sensory inputs in the generation of integrated output responses.

PMID- 8577383
TI  - The pupillary light response: assessment of function mediated by intracranial
      retinal transplants.
AB  - We have adapted a pupillometry measurement system to test the functional efficacy
      of retinae previously transplanted over the midbrain of neonatal rats in
      mediating a pupillary light reflex in the host eye. This has permitted us to
      examine factors influencing various parameters of the response, and to study
      transplant-mediated responses in comparison with responses mediated by way of the
      normal consensual pathway. Despite the unusual location of these transplanted
      retinae and the absence of supportive tissues normally associated with retinae in
      situ, it is clear that pupilloconstriction in the host eye can be elicited by
      transplant illumination. Under the optimal conditions here defined, response
      parameters for individual animals were stable with repeated testing over extended
      periods. When considered as individual cases, response amplitude, constriction
      rate and response latency were intensity dependent, although responses elicited
      by transplant illumination were less sensitive than normal, typically by 2-3 log
      units. Large-amplitude transplant-mediated pupillary responses could, however, be
      elicited repeatedly throughout long trains of stimuli, unlike normal responses,
      which rapidly failed to recover to baseline under similar test conditions.
      Finally, even though some cellular elements of the visual cycle are absent in
      transplanted retinae, pupilloconstriction in the host eye could be elicited
      repeatedly by transplant illumination as long as two years after transplantation
      took place. These observations indicate the applicability of this preparation as
      an assay for the effects of experimental manipulations on information processing
      and response plasticity in the visual system, and as a tool for examining, in
      general, the necessary conditions for optimal function of grafts that work by
      synthesizing and relaying neural signals.

PMID- 8577384
TI  - Correlation between dendrodendritic synapses of adrenergic type and synaptically
      evoked hyperpolarization in the sympathetic ganglion of adult rats.
AB  - Intracellular recording and labeling with biocytin followed by electron
      microscopic observation were used to examine the nature and the morphological
      basis of a synaptically evoked hyperpolarization following spikes in the rat
      superior cervical ganglion neurons. A large hyperpolarization (the amplitude > 8
      mV; the duration > 1 s following spikes) was elicited by repetitive stimulation
      of the preganglionic nerves in 8% of cells examined (n = 50). The alpha 2
      adrenoceptor antagonist, yohimbine, reversibly attenuated the hyperpolarization,
      without affecting spikes. A nicotinic antagonist, hexamethonium, blocked both the
      hyperpolarization and spikes. Atropine had no effect of these responses. Electron
      microscopic observation of dendrites of these cells revealed that they received
      synaptic inputs of adrenergic type besides a cholinergic one from the
      preganglionic axons. Some dendrites served as presynaptic elements. These results
      strongly suggest that the hyperpolarization is an inhibitory postsynaptic
      potential and that this disynaptic response to the preganglionic stimulation is
      mediated mainly by two transmitters, acetylcholine and noradrenaline that are
      released from axodendritic and dendrodendritic synapses, respectively. We
      conclude that there appears to be an adrenergic inhibitory local circuit that
      modulates cholinergic transmission in the sympathetic ganglia.

PMID- 8577385
TI  - Galanin expression in carotid body afferent neurons.
AB  - The present study examined expression and plasticity of the neuropeptide,
      galanin, in carotid body afferent neurons in the petrosal ganglion of the adult
      rat. The pattern of galanin expression was compared with that of tyrosine
      hydroxylase, a selective marker of dopaminergic carotid body afferents in the
      petrosal ganglion. In normal animals, only 3% of tyrosine hydroxylase-containing
      petrosal ganglion neurons co-expressed galanin. Retrograde labeling studies, in
      which FluoroGold was injected into the vascularly isolated carotid body,
      demonstrated that all tyrosine hydroxylase-positive-galanin-positive cells in the
      petrosal ganglion project to this target. In addition, however, we unexpectedly
      found that galanin expression was markedly increased in the petrosal ganglion
      following FluoroGold injection into the carotid body. On the other hand, tyrosine
      hydroxylase expression was unchanged, indicating that monoaminergic and
      peptidergic traits can be differentially regulated in these cells. In summary,
      these data demonstrate that monoaminergic chemoafferent neurons can co-express a
      peptidergic trait, similar to catecholaminergic neurons within the central and
      autonomic nervous systems, and that these cells retain the potential for
      phenotypic plasticity in adulthood.

PMID- 8577386
TI  - Spontaneous synchronized neural activity in decerebrate gallamine-paralysed cats.
AB  - In decerebrate cats paralysed with gallamine, over a period of several days there
      develops a remarkable synchronization of discharge in widely different motor
      nerves throughout the body, including intercostal nerves and limb nerves. These
      discharges are also in synchrony with slow waves approximately 100 ms in duration
      in the inferior olive. The slow waves and discharges are at first irregular and
      only weakly synchronized, but become increasingly strongly synchronized and by
      about the fourth day exhibit a strong 6-8 Hz rhythm. The degree of
      synchronization is greater the lower the end-tidal CO2 concentration. Transection
      of the spinal cord at a high cervical level breaks the synchrony and may abolish
      the discharge in the nerves, but the slow waves in the inferior olive continue
      rhythmically. It was shown, however, that gallamine injected subdurally at
      cervical vertebra 7 or lumbar vertebra 7 has a direct excitatory action on the
      spinal cord. Slow waves in the inferior olive are elicited by gallamine in the
      decerebrate, spinalized and decerebellectomized cat, and therefore must originate
      in the brainstem. Gallamine is known to act directly on olivary neurons and the
      slow waves may originate in the inferior olive, but further experiments are
      needed to determine what other structures it affects. The condition of the cat a
      few days after decerebration and paralysis resembles the clinical condition of
      reticular reflex myoclonus and it is suggested that the genesis of the myoclonus
      may be similar in the two conditions.

PMID- 8577387
TI  - [3H]methoxytetrabenazine: a high specific activity ligand for estimating
      monoaminergic neuronal integrity.
AB  - The properties as well as the distribution of high specific activity alpha-[O
      methyl-3H]methyoxytetrabenazine binding to the synaptic vesicular monoamine
      transporter were studied autoradiographically in rat brain sections. Saturation
      analysis revealed [3H]methoxytetrabenazine interaction with a homogeneous
      population of striatal sites (Hill coefficient 1.00 +/- 0.05), with an apparent
      equilibrium dissociation binding constant of 3.9 +/- 0.4 nM and a maximal binding
      capacity of 1.2 +/- 0.1 fmol/micrograms protein. Highest levels of
      [3H]methoxytetrabenazine binding sites were observed in regions richly innervated
      by the monoamine systems. In the presence of 1 microM concentrations of a variety
      of competing drugs, only reserpine significantly inhibited
      [3H]methoxytetrabenazine binding. The presynaptic nigrostriatal location of
      [3H]methoxytetrabenazine binding was demonstrated by unilateral lesion of the
      median forebrain bundle with 6-hydroxydopamine. The resulting decrease of
      striatal [3H]methoxytetrabenazine binding showed an excellent correlation with
      tyrosine hydroxylase-positive neuron density in the substantia nigra pars
      compacta (r2 = 0.96; P < 0.001). The present studies demonstrate that in vitro
      [3H]methoxytetrabenazine binding is a reliable, quantitative marker of the
      synaptic vesicular monoamine transporter. Further, it is indicated that
      [3H]methoxytetrabenazine binding provides an accurate assessment of monoamine
      neuronal losses and may thus be of great value in future studies of
      neurodegenerative diseases.

PMID- 8577388
TI  - The motoneuron degeneration in the wobbler mouse is independent of the
      overexpression of a Bcl2 transgene in neurons.
AB  - The wobbler mouse mutation, an autosomal recessive mutation, leads to motoneuron
      degeneration in early post-natal development. Transgenic mice in which neurons
      overexpress human bcl2 transgene have been generated: the overexpression of bcl2
      reduces the neuron loss during naturally occurring and experimentally-induced
      cell deaths. In the present study, we generate mice co-expressing the wobbler
      mutant gene and the bcl2 transgene in order to determine the effects of Bcl2
      overexpression on the neurodegenerative disorders of the wobbler mouse. The
      clinical signs of the disease (weakness, tremor, small size) as well as
      biochemical and histological parameters (choline acetyltransferase (ChAT)
      activity in muscles, gliosis in spinal cord) are similar in bcl2 positive and
      negative wobbler mice. These results point to the fact that the neuron-specific
      expression of the human bcl2 transgene does not correct the effects of the
      wobbler mutation.

PMID- 8577389
TI  - Developmental upregulation of the neural cell adhesion molecule VASE exon in
      slice cultures of rat hippocampus.
AB  - The factors limiting axonal growth in the mature CNS are poorly understood. It
      has been shown that the neural cell adhesion molecule VASE exon (variable
      alternative spliced exon) is one of the factors that may account for the
      downregulation of neurite outgrowth. Here we demonstrate that the developmental
      upregulation of the VASE exon is preserved in slice cultures of hippocampus,
      making these cultures a useful model to study the regulation of VASE and age
      dependent growth processes in an organotypic environment.

PMID- 8577390
TI  - Neurite outgrowth of murine cerebellar granule cells can be enhanced by
      aniracetam with or without alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid (AMPA).
AB  - To assess the neurotrophic effects of a nootropic drug, aniracetam, we studied
      neurite extension of mouse cerebellar granule cells in culture with low or with
      high K+ under different combinations of drugs and then immunohistochemically
      stained the cells with an antibody against L1, a neural cell adhesion molecule on
      cerebellar granule cells. Quantitative analyses using parameters of the total
      neurite length, maximal neurite length and number of branches disclosed that
      aniracetam, in the presence of high K+ and alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA), significantly enhanced neurite extension of
      cultured granule neurons. Aniracetam alone also stimulated neurite extension of
      cerebellar granule cells at a longer period of culture with low K+ showing a bell
      shaped dose response curve with maximal effects at 10 microM. Aniracetam may
      influence remodeling of the neural network after injury.

PMID- 8577391
TI  - Prefrontal cortex projections to the basilar pons in rhesus monkey: implications
      for the cerebellar contribution to higher function.
AB  - The feedforward limb of the cerebrocerebellar system is directed largely through
      the corticopontine pathway. We determined the extent to which higher order
      corticopontine projections are derived from prefrontal associative cortices by
      injecting anterograde tracers into multiple prefrontal regions in rhesus monkeys.
      Most prefrontopontine projections were derived from the dorsolateral and
      dorsomedial convexities, including areas 8A, 46 dorsal, 9, and 10; and lighter
      projections arose from medial and ventrolateral cortices. These findings
      strengthen the observation that the cerebrocerebellar system incorporates
      associative cerebral regions, and they enhance the notion that the cerebellum
      participates in the organization of cognitive function.

PMID- 8577392
TI  - Mapping of sound direction in the trout lower midbrain.
AB  - In the trout lower midbrain 35% of the auditory neurons are directionally
      selective (DS). Most of these neurons have a higher directional selectivity than
      the sensory hair cells. DS units and non-DS units occur in vertical clusters,
      with the former more dorsally. The direction of preference is topographically
      mapped. Apparently, auditory space mapping is a common feature in the midbrain of
      vertebrates.

PMID- 8577393
TI  - A mutation in codon 717 of the amyloid precursor protein gene in an Australian
      family with Alzheimer's disease.
AB  - DNA from the probands of seven Australian families with hereditary Alzheimer's
      disease was screened for the presence of known mutations in the amyloid precursor
      protein (APP) gene on chromosome 21 using single stranded conformational
      polymorphism (SSCP) analysis [14]. One subject was found to have a mutation
      causing a Val-->Ile substitution at position 717. This was confirmed by
      restriction enzyme digestion and sequencing. The mutation has been found in both
      the other affected family members available for study and in two at-risk
      relatives. It was not present in the only living unaffected relative who has
      passed the usual age of onset in this family. There is so far no evidence that
      apolipoprotein E (APOE) genotype influences age of onset in this family, though
      numbers are small. Two other families with autopsy confirmation and age of onset
      in the fifth decade had no APP mutation and are thought likely to have a mutation
      on chromosome 14 on the basis of their earlier onset age.

PMID- 8577394
TI  - Suppression of rhythmic discharges of medullary neurones in organotypic cultures
      of new-born rats by calcium antagonists.
AB  - The contribution of transmembrane calcium flux to the generation of periodic
      bioelectric activity in cultured organotypic medullary tissue of 6 day old rats
      was determined by adding calcium antagonists (CA) to the recording saline and by
      lowering the calcium concentration of this saline. Organic CA flunarizine and
      verapamil (50-100 mumol/l) reversibly suppressed rhythmic discharge and
      diminished the CO2 response of medullary neurones within 30-60 min. Inorganic CA
      cobalt and magnesium exerted the same effects within a few minutes. After
      lowering the calcium concentration rhythmic activity became unstable, but
      recovered on exposure to increased CO2 concentration, the excitatory effect of
      which was strongly reduced. These findings point to a significant role for
      transmembrane calcium flux and intracellular calcium concentration in sustaining
      both periodic activity and the CO2 response of medullary neurones.

PMID- 8577396
TI  - Involvement of potassium and calcium channels at the locus coeruleus in fentanyl
      induced muscular rigidity in the rat.
AB  - Previous work from our laboratory suggested that Go alpha protein at the locus
      coeruleus (LC) may be involved in the signal transduction process that underlies
      muscular rigidity induced by fentanyl. The present study further evaluated the
      roles of K+ and L-type Ca2+ channels, gating of which is known to be associated
      with activation of Go alpha protein, in this process, using Sprague-Dawley rats
      anesthetized with ketamine. Bilateral microinjection into the LC of
      tetraethylammonium chloride (100 or 200 pmol), a K+ channel blocker, and S(-)-Bay
      K 8644 (0.5 nmol), a Ca2+ channel activator, produced significant antagonization
      of the EMG activation elicited by fentanyl (100 micrograms/kg, i.v.), as recorded
      from the sacrococcygeus dorsalis lateralis muscle. On the other hand, local
      application to the bilateral LC of diazoxide (10 or 20 nmol), an ATP-dependent K+
      channel activator, and nifedipine (0.25 or 0.5 pmol), a L-type Ca2+ channel
      blocker, was ineffective in blunting fentanyl-induced muscular rigidity. These
      results suggest that activation of K+ channels and/or inhibition of L-type Ca2+
      channels secondary to triggering of the Go alpha protein at the LC may underlie
      the signal transduction process in the mediation of fentanyl-induced muscular
      rigidity.

PMID- 8577397
TI  - N-methyl-4-phenylpyridinium and an endogenously formed analog, N-methylated beta
      carbolinium, inhibit striatal tyrosine hydroxylation in freely moving rats.
AB  - The effects of N-methyl-4-phenylpyridinium (MPP+) and its endogenous analog, 2,9
      di-methyl-norharmanium (2,9-Me2NH+), on in vivo tyrosine hydroxylation were
      evaluated in freely moving rats. MPP+ gradually but almost completely reduced
      tyrosine hydroxylation, even at a dose as low as 0.05 mM. This effect was
      considered to be caused by the inhibition of tyrosine hydroxylase (TH)
      activation. On the contrary, 1 mM 2,9-Me2NH+ rapidly reduced 3,4
      dihydroxyphenylalanine production to 10% of the basal level only during its
      perfusion, indicating direct inhibition of TH activity. The present study
      revealed that MPP+ and 2,9-Me2NH+ were taken up into dopaminergic neurons and
      then inhibited in vivo dopamine synthesis prior to cell death possibly in
      different manners.

PMID- 8577395
TI  - Serotonin-induced 5-HT1A receptor desensitization in C6BU-1 glioma cells
      transfected with 5-HT1A receptor gene.
AB  - In this study, it has been clearly demonstrated that a selective 5
      hydroxytryptamine (5-HT)1A agonist, 8-OH-2-(di-n-propylamino)-tetraline (8-OH
      DPAT, 1 microM) significantly inhibited forskolin (10 microM)-stimulated cyclic
      AMP (cAMP) accumulation in the C6BU-1 cells transfected with 5-HT1A receptor
      gene. Further, this 8-OH-DPAT-induced inhibition of forskolin-stimulated activity
      was significantly attenuated after pre-exposure to 5-HT (10 microM) for 12 h.
      Spiperone (10 microM), a 5-HT1A and 5-HT2A antagonist, prevented 5-HT-induced
      desensitization of 5-HT1A receptor, but a selective 5-HT2A receptor antagonist,
      ketanserin, did not. In addition, pre-exposure to a selective 5-HT2A agonist, 1
      (2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 10 microM), for 24 h did not
      alter the inhibitory effect of 8-OH-DPAT on forskolin-stimulated cAMP
      accumulation in these transfected cells, suggesting that prolonged exposure to 5
      HT induced 5-HT1A receptor desensitization, mediated by 5-HT1A receptor but not 5
      HT2A receptors.

PMID- 8577399
TI  - 5,7-Dihydroxytryptamine uptake discriminates living serotonergic cells from
      dopaminergic cells in rat midbrain culture.
AB  - Dissociated cells from embryonic rat midbrain develop in dissociated culture into
      glutamatergic, GABAergic and aminergic cells. The autofluorescent serotonin
      analogue, 5,7-dihydroxytryptamine (5,7-DHT), is taken up by a small population of
      cells that is immunoreactive to 5-hydroxytryptamine. Tyrosine hydroxylase
      immunoreactive cells do not accumulate 5,7-DHT. 5,7-DHT uptake, therefore, is
      well suited for the identification of living serotonergic cells and their
      discrimination from dopaminergic cells.

PMID- 8577398
TI  - Amyloid beta-peptide in cerebrospinal fluid in individuals with the Swedish
      Alzheimer amyloid precursor protein mutation.
AB  - The neuropathological hallmarks of Alzheimer's disease (AD) are amyloid
      containing plaques and neurofibrillary tangles. The main constituent of senile
      plaques is amyloid beta-peptide (A beta) and in recent years, pathogenic
      mutations in the amyloid precursor protein (APP) gene have been discovered in
      some AD families. The APP670/671 mutation, found in a Swedish AD family, has
      revealed over-production of A beta as one pathogenic mechanism for the
      development of AD. In the present study we have used an immunoassay to measure A
      beta levels in cerebrospinal fluid (CSF) from APP670/671 mutation-carriers and
      non-carriers. A correlation was seen between decrease in A beta levels and
      duration of disease although no difference was found in levels of A beta between
      the groups (14.5 +/- 3.3 ng/ml versus 14.9 +/- 2.3 ng/ml).

PMID- 8577400
TI  - Serotoninergic modulation of excitability in area CA1 of the in vitro rat
      hippocampus.
AB  - Intra- and extracellular recordings from the in vitro rat hippocampal slice
      preparation have been used to investigate the influence of serotoninergic,
      adrenergic and cholinergic receptor antagonists on the excitability of CA1
      pyramidal neurones. The serotonin receptor antagonist 4-amino-N-(1
      azabicyclo[2.2.2]oct-3yl)-5-chloro-2- methoxybenzamide(E)-2-butenedioate
      (zacopride, 100 microM) produced multiple population spikes on the
      orthodromically evoked field potential, in contrast to the lack of effect of
      another serotonin antagonist 1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,5
      dichlorobenzoate (MDL 72222, 30 microM), as well as the cholinergic antagonists
      atropine (10 microM) and hexamethonium (100 microM) and the noradrenergic
      antagonist atenolol (10 microM). Monosynaptic inhibitory postsynaptic potentials
      (IPSPs) recorded in the presence of the glutamatergic antagonists 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX, 10 microM) and ketamine (50 microM) were
      recorded from CA1 pyramidal neurones. Zacopride (100 microM) and MDL 72222 (30
      microM) both reduced the isolated IPSP to 54 +/- 9% (n = 8) and 78 +/- 4% (n =
      3), respectively. Neither of the cholinergic antagonists had any effect, while
      atenolol reduced the IPSP to 87 +/- 3% (n = 7) of the control IPSP. We propose
      that the difference in action of zacopride and MDL 72222 on the field potentials
      is due to zacopride activating postsynaptic 5HT4 receptors on the pyramidal
      neurone, thereby reducing a Ca(2+)-activated K(+)-conductance. This, in
      combination with a 5HT3 receptor-mediated reduction in gamma-aminobutyric acid
      (GABA)-ergic inhibition, leads to an increase in pyramidal cell excitability
      evident as epileptic field potentials.

PMID- 8577401
TI  - Chemical topography of efferent projections from the median preoptic nucleus to
      pontine monoaminergic cell groups in the rat.
AB  - This study examined efferent output from the median preoptic nucleus (MnPO) to
      pontine noradrenergic and serotonergic cell groups using an anterograde tracing
      technique (Phaseolus vulgaris leucoagglutinin, PHA-L) combined with glucose
      oxidase immunocytochemistry to serotonin (5-HT) or to dopamine-beta-hydroxylase
      (DBH). Injections of PHA-L into the ventral MnPO resulted in moderate axonal
      labeling within the region of the B7 and B8 serotonergic groups in the dorsal
      raphe. PHA-L labeled fibers and punctate processes were observed in close
      apposition to many of the 5-HT immunoreactive neurons in these regions. In
      contrast, sparse terminal labeling was found within the B5 group in the raphe
      pontis nucleus, and only trace fiber labeling observed in the B3 and B6 groups.
      Efferents from the MnPO also provided moderate innervation to the A6 and A7
      noradrenergic groups. PHA-L labeled punctate processes were found most frequently
      in close apposition to DBH-immunoreactive neurons at mid- to caudal levels of the
      locus coeruleus. Some labeled axons were also present within the A7 and A5
      groups. Additionally, a close apposition between labeled MnPO efferents and 5-HT
      fibers within the lateral parabrachial nucleus was observed. The results indicate
      the MnPO provides a topographic innervation of monoaminergic groups in the upper
      brainstem.

PMID- 8577402
TI  - Striatal expression of substance P and methionin-enkephalin in genes in patients
      with Parkinson's disease.
AB  - The striatal expression of substance P (SP) and methionin-enkephalin (met-enk)
      genes was studied post mortem by in situ hybridization in patients with
      Parkinson's disease and a group of control subjects. No significant difference in
      striatal expression of these two neuropeptide messenger RNAs (mRNAs) was found in
      the patients compared with control subjects. This contrasts with animal models of
      parkinsonism, where expression of SP mRNA is decreased and met-enk mRNA
      increased. Possible explanations include: (1) compensatory mechanisms, which may
      develop during the long term evolution of Parkinson's disease; (2) normalized
      expression of the two genes resulting from chronic L-DOPA therapy.

PMID- 8577403
TI  - pH-dependent modulation of N-methyl-D-aspartate receptor-mediated synaptic
      currents by histamine in rat hippocampus in vitro.
AB  - Modulation of excitatory postsynaptic currents by histamine was examined using
      whole cell recording methods in the CA1 region of slices of rat hippocampus.
      Histamine affected the N-methyl-D-aspartate (NMDA) component of the synaptic
      current in a pH-dependent manner: at lowered pH (7.2) it enhanced the NMDA
      mediated synaptic currents while at raised pH (7.6) it reduced them. At a pH of
      7.4 there was no significant action of histamine. Histamine failed to alter the
      non-NMDA component of the synaptic current. These results indicate that histamine
      acts at a postsynaptic site to modulate NMDA mediated synaptic currents in a pH
      dependent manner. This mechanism may have important implications for the
      pathophysiology of shifts in extracellular pH.

PMID- 8577404
TI  - Effect of chemical stimulation of the dorsal raphe nucleus on cerebral blood flow
      in rat.
AB  - We have previously shown that electrical stimulation of the dorsal raphe nucleus
      (DRN) can increase or decrease cerebral blood flow (CBF). We now sought to
      determine whether the CBF responses are mediated by DRN neurons or fibers of
      passage. In anesthetized rat, the DRN was stimulated chemically (L-glutamate,
      kainate) and CBF in parietal cortex was measured by laser-Doppler flowmetry.
      Microinjection of kainate (5 nmol), but not L-glutamate, into DRN increased CBF
      (28 +/- 22%; P < 0.05). Decreased CBF to DRN stimulation was not observed. We
      conclude that stimulation of DRN neurons increases CBF.

PMID- 8577406
TI  - Overview and mechanisms of iron regulation.
AB  - There are two major disturbances of iron balance: iron deficiency and iron
      overload. Iron-deficiency anemia is a major problem in developing countries and
      affects between 500 million and 600 million people worldwide. While iron overload
      is much less prevalent, it has a number of major pathologic sequelae and there
      have been recent suggestions that even modest increases in the body's iron stores
      may have pathologic associations. To understand the ways in which iron balance
      can be disturbed, it is necessary to have an understanding of how losses from the
      body are matched by the absorption of iron in different dietary settings as well
      as the limits of this regulatory control.

PMID- 8577405
TI  - Increased cerebrospinal fluid pyruvate levels in Alzheimer's disease.
AB  - Impaired energy metabolism is an early, predominant feature in Alzheimer's
      disease. In order to find out simple, reliable 'in vivo' markers for the clinical
      biological typization of the disorder, we measured cerebrospinal fluid (CSF)
      glucose, lactate and pyruvate levels in patients suffering from dementia of
      Alzheimer type (DAT) and in healthy elderly controls. DAT group showed remarkably
      higher levels of pyruvate (P = 0.01), with no overlap with the values obtained in
      controls. CSF pyruvate levels were also significantly associated with the
      severity of dementia. Therefore, CSF pyruvate levels neatly separate DAT patients
      from controls, having also pathogenetic value.

PMID- 8577407
TI  - Methods to assess iron status in various NHANES surveys.
AB  - This paper summarizes iron status measurements included in the three cross
      sectional National Health and Nutrition Examination Surveys (NHANES) completed to
      date, as well as a special study of Hispanics, known as the Hispanic Health and
      Nutrition Examination Survey (HHANES). Approaches for defining iron status in the
      population based on these measurements are also described as well as issues in
      comparing iron status data between surveys, using NHANES II and III data as an
      example.

PMID- 8577408
TI  - Iron overload: prevalence and impact on health.
AB  - Clinical manifestations attributable to the damaging effects of iron occur when
      the total body iron is 5-10 times higher than normal. In adults this degree of
      iron overload occurs in hereditary hemochromatosis, a human leukocyte antigen
      (HLA)-linked autosomal recessive disorder, as well as in secondary iron-overload
      conditions.

PMID- 8577409
TI  - ISIS 4: clinical controversy regarding magnesium infusion, thrombolytic therapy,
      and acute myocardial infarction.
AB  - Magnesium (Mg) infusions over 24 hours were given to patients with suspected
      acute myocardial infarction (AMI) at least 2 hours after thrombolysis. Patients
      showed no benefit and even some increased risk in contrast to reduction in
      mortality obtained by Mg therapy in smaller trials. Results of all of the studies
      were pooled and statistically analyzed, according to a fixed-effects model that
      is inappropriate for studies of different protocols. The panel concluded that
      further study of Mg in AMI is not needed. This conclusion has been questioned.

PMID- 8577410
TI  - Influence of altered body weight on energy expenditure.
AB  - Long-term metabolic studies indicate that over-feeding underfeeding to gain and
      lose body weight produce consistent increases and decreases in energy
      expenditure. These changes occur in both lean and obese subjects and cause
      deviations from the normal relationship between energy expenditure and metabolic
      body size. The low energy expenditure/metabolic body size in the reduced obese
      may contribute to the difficulty in maintaining the reduced body weight.

PMID- 8577411
TI  - Are saturated fatty acids essential in the diet?

PMID- 8577412
TI  - Zinc and human health.

PMID- 8577413
TI  - Lowered energy intake and dietary macronutrient balance: potential consequences
      for micronutrient status.

PMID- 8577414
TI  - Magnesium status and health.

PMID- 8577415
TI  - The importance of vitamin E in reducing cardiovascular risk.

PMID- 8577416
TI  - Folate and neural tube defects.

PMID- 8577417
TI  - Total nutrient intake and ready-to-eat cereal consumption of children and young
      adults in the Bogalusa Heart Study.

PMID- 8577418
TI  - Micronutrient status and aging.

PMID- 8577419
TI  - Frustration over job redesign.

PMID- 8577420
TI  - Variations on the capitation theme.

PMID- 8577422
TI  - It's politics, not policy ... people!

PMID- 8577423
TI  - Home care liability--Part II.

PMID- 8577421
TI  - Competition in the subacute care market: who will prevail?

PMID- 8577424
TI  - Devising and delivering objectives for disease state management.
AB  - Comprehensive, objective plans of clinical care that reflect the optimal
      diagnosis and treatment must be developed. Standardized plans of patient care
      that are centered around a specific disease entity meet outcomes management and
      maximize health delivery quality. This integration is embodied in the philosophy
      of disease state management.

PMID- 8577425
TI  - 2,000 patients relate their hospital experiences.
AB  - This paper uses the reports of more than 2,000 adult medical/surgical patients
      drawn from 17 randomly selected hospitals within a midwestern major metropolitan
      area to (1) describe the differences between patients' reports and ratings of
      car, (2) determine the influence of service failures on patients' recommendations
      of a hospital to family and friends and (3) suggest constructive managerial
      responses to current patient satisfaction monitoring strategies.

PMID- 8577426
TI  - Management restructuring: toward a leaner organization.
AB  - The drive to create integrated delivery networks has given even further momentum
      to management restructuring. Through centralization of decision making within
      networks, speed and flexibility are needed to make the difficult modifications
      required to achieve standardization and general overhead savings. Two hospitals,
      Carondelet St. Mary's and Carondelet St. Joseph's merged under a single
      administrative team and one Vice President of Patient Care Services. Outcomes of
      this restructuring were monetary savings, but also learning how to plan and carry
      out major management restructuring. The values, the process and the outcomes one
      year post implementation, and the keys to success in the management restructuring
      effort are the subjects of this article.

PMID- 8577427
TI  - Regulatory requirements and the multi-task worker.
AB  - This paper describes a framework for compliance the regulatory agency
      requirements and internal service standards in response to service
      decentralization and institution of a multi-task environmental worker role.
      Initiation and maintenance of the compliance system and the coordination of
      institutionally specific service standards are described. Five keys for success
      are detailed.

PMID- 8577428
TI  - Recruitment and orientation of older volunteers in extended care.
AB  - Older volunteers can make miracles happen as they have more time than younger
      persons and staff to listen and to give patients and residents personal
      attention. Recruitment and orientation of older volunteers is the first step and
      must be ongoing, as turnover may be high. Orientation that focuses on the goals
      of the volunteer program and a few important concepts in relating to patients and
      residents may be all that is needed to get an older volunteer started.

PMID- 8577429
TI  - Effective ED complaint management.
AB  - Handling patient complaints is possibly one of the most delicate tasks any
      manager must face. Although managing patient complaints is never a pleasant
      experience, a detailed plan can make it easier and more uniform, resulting in
      less stress and anxiety. Before improvements can be accomplished, deficiencies in
      the system must be corrected. Only after the department's processes have been
      deemned stable can the qualiuty of care be improved and the customer satisfied.

PMID- 8577430
TI  - Developing a simulated disaster.
AB  - Disaster drills are often accomplished through paper exercises and questionable
      preparation of staff. A successful simulated disaster involves creativity,
      planning, the players, disaster day and debriefing.

PMID- 8577431
TI  - Improving a perioperative service.
AB  - A collaborative process between graduate nursing students and managers in a
      rural, midwestern hospital resulted in an updated perioperative service area. A
      proposal targeted three areas: physical layout, patient education and
      documentation.

PMID- 8577432
TI  - Executive leave: avoiding the pitfalls.
AB  - A leave of absence must be carefully planned to avoid any potential pitfalls. A
      successful transfer of power when assigning a temporary replacement requires
      trust, confidence and excellent communication. A director and an assistant
      director who work with over 300 staff share their experience.

PMID- 8577433
TI  - Nursing informatics certification.

PMID- 8577434
TI  - Contingency plans: employment relationships in the late '90s.

PMID- 8577435
TI  - Let's trash the care plan!

PMID- 8577436
TI  - The search for nursing leadership: departing from the traditional.

PMID- 8577437
TI  - Nursing staff organizational development.

PMID- 8577438
TI  - A collaborative practice model in a community hospital.

PMID- 8577439
TI  - Your license and mine.

PMID- 8577440
TI  - Is your safety training program accessible?

PMID- 8577441
TI  - Selecting chemical protective clothing.

PMID- 8577442
TI  - Dry particulate protection: new technologies mean more choices.

PMID- 8577443
TI  - Slip-and-fall accidents.

PMID- 8577444
TI  - Festschrift on the occasion of Otto Hockwin's 70th Birthday.

PMID- 8577445
TI  - Usefulness of Scheimpflug photography to follow up Wilson's disease.
AB  - A 24-year old female with ocular changes (Kayser-Fleischer ring and sunflower
      cataract) indicating Wilson's disease was followed up from 9 years of age with
      anterior eye segment image documentation by Scheimpflug photography. A low copper
      diet and systemic D-penicillamine were administered after the initial diagnosis
      of Wilson's disease. During a 15-year follow-up period, the yellowish/brown
      colored granular opacification on the anterior lens capsule and/or in the capsule
      has mostly disappeared and instead, the same type of opacification has emerged on
      the posterior lens capsule, showing rather progressive changes compared with the
      initial findings. These changes which had developed in the lens during the past
      15 years were difficult to detect by slit lamp examination alone, but they were
      clearly revealed by Scheimpflug slit images. To our knowledge this is the first
      case report on ocular changes disclosed through the application of a newly
      developed anterior eye segment examination. Ergo, Scheimpflug photography is
      valuable for follow-up studies of ocular complications seen in patients with
      Wilson's disease.

PMID- 8577446
TI  - Anterior chamber angle biometry: a comparison of Scheimpflug photography and
      ultrasound biomicroscopy.
AB  - Scheimpflug photography and ultrasound biomicroscopy allow measurement of
      anterior chamber angle width. To analyze the value of both diagnostic tools,
      measurements of the same subjects were correlated. Anterior chamber angle width
      in both eyes of 20 volunteers without any ophthalmological case history was
      measured in eight meridians. Scheimpflug photographs were recorded on Kodak T-max
      400 black-and-white film using a Topcon SL-45 camera. Measurement of chamber
      angle was done with the aid of a self-programmed PC software. Ultrasound
      biomicroscopic measurements were obtained using a Humphrey UBM 840 system with a
      50-MHz transducer. The chamber angle was measured as described by Pavlin et al.
      The data of both methods were correlated and analysed for statistically
      significant differences using a paired t test (level of significance p < or =
      0.05). Both methods showed similar changes in chamber angle width and were able
      to document a variation in angle width with regard to location. The correlation
      averaged at 0.64. In 4 meridians significant differences were found between the
      two methods. Scheimpflug photography, however, is unable to visualize directly
      the angle itself. Both methods are limited by the fact that the angle is defined
      by curvilinear structures, i.e. posterior corneal surface and anterior iris
      surface. Scheimpflug photography is able to document changes in angle
      configuration. Ultrasound biomicroscopy, however, is a more precise method,
      because it allows direct documentation of all structures involved in chamber
      angle configuration.

PMID- 8577447
TI  - Use of non-subjective analysis of lens transparency in experimental radiation
      cataract research.
AB  - Historically the major impediment to radiation cataract follow-up has been the
      necessarily subjective nature of assessing the degree of lens transparency. This
      has spurred the development of instruments which produce video images amenable to
      digital analysis. One such system, the Zeiss Scheimpflug slit lamp measuring
      system (SLC), was incorporated into our ongoing studies of radiation
      cataractogenesis. It was found that the Zeiss SLC measuring system has high
      resolution and permits the acquisition of reproducible images of the anterior
      segment of the eye. Our results, based on about 650 images of lenses followed
      over a period of 91 weeks of radiation cataract development, showed that the
      changes in the light scatter of the lens correlated well with conventional
      assessment of radiation cataracts with the added advantages of objectivity,
      permanent and transportable records and linearity as cataracts become more
      severe. This continuous data acquisition, commencing with cataract onset, can
      proceed through more advanced stages. The SLC exhibits much greater sensitivity
      reflected in a continuously progressive severity thereby avoiding the artifactual
      plateaus in staging which occur using conventional scoring methods.

PMID- 8577448
TI  - The blood-ocular barrier in type I diabetes without diabetic retinopathy:
      permeability measurements using fluorophotometry.
AB  - For the evaluation of a possible malfunction of the blood-retinal (BRB) and the
      blood-aqueous barrier (BAB) in type I diabetes without manifest angiopathy, after
      i.v. injection of sodium fluorescein, the permeability of BRB (P) and the
      diffusion coefficient of BAB [P(a)] were studied simultaneously by
      fluorophotometry in 34 eyes of 34 type I diabetics (HbA1c = 6.6 +/- 0.9%) without
      retinopathy whose ages ranged from 19 to 38 years (30.5 +/- 5); diabetes'
      duration was between 5 and 18 years. Fluorescein angiography was performed to
      exclude nonperfused areas. In all, 34 eyes of 34 healthy volunteers whose ages
      ranged between 23 and 34 years (28.5 +/- 3.3) served as controls; in this group,
      fluorophotometry was performed twice to evaluate reproducibility. The mean BAB
      diffusion coefficient in diabetics [P(a) = 5.3 +/- 1.8/min] was significantly
      increased (p = 0.00003) as compared to controls [P(a) = 3.7 +/- 0.7/min]; BRB
      permeability in diabetes (P = 3.2 +/- 1.4 x 10(-7) cm/s) was raised with this
      elevation being of lower significance (p = 0.019; controls: P = 2.6 +/- 0.7 x 10(
      7) cm/s). We found a decrease in BRB permeability depending on diabetes' duration
      (r = -0.15; p = 0.007) that was not significant in BAB (r = -0.1; p = 0.24). No
      correlation was found to exist between permeability and HbA1c values either in
      BAB or in BRB. The reproducibility in controls was 9% in BRB determinations and
      12% in BAB measurements. These results may suggest that early structural
      alterations without the manifestation of retinopathy possibly cause elevation in
      BRB permeability and are even more obvious in BAB permeability. Whereas the
      reliability of vitreous fluorophotometry in detecting early BRB malfunction has
      to be judged critically, anterior segment fluorophotometry is a reliable
      procedure for the monitoring of BAB affection in type I diabetes without
      retinopathy.

PMID- 8577449
TI  - Plasma sterilization of selected ophthalmic instruments for combined intraocular
      surgery.
AB  - Plasma sterilization is a nontoxic fast procedure for thermolabile and
      thermostable microsurgical instruments. We report data on the microbicidal
      effectiveness for daily routine surgical instruments like steel scissors,
      trephination devices, microstripper and Vitro-Cat as well as
      irrigation/aspiration instruments. When these instruments were cleaned from blood
      and saline, and when H2O2 intensifiers (adapters) were applied where necessary
      plasma sterilization proved to be a microbiologically safe procedure with legally
      adequate reduction factors of > 6 log.

PMID- 8577450
TI  - Non-toxic concentrations of cephem antibiotics for intravitreal application-
      evaluation by in vitro electroretinogram.
AB  - Non-toxic concentrations of ceftazidime (CAZ), cefuzonam sodium (CZON) and
      cefmetazole sodium (CMZ) for intravitreal use were assessed by the
      electroretinogram in in vitro perfused eyecups of albino rabbits. None of the a
      wave, the b-wave and the oscillatory potentials deteriorated with 300 microM CAZ,
      300 microM CZON or 500 microM CMZ. The oscillatory potentials were delayed and/or
      diminished at the concentration which did not change the a- and b-waves (500
      microM and 1.0 mM for CAZ and CZON, 1.0 mM for CMZ). Thus, the oscillatory
      potentials were more vulnerable to these chemicals than the a- and b-waves. Not
      only the classical a- and b-waves, but also the oscillatory potentials should be
      examined in retinal toxicology studies by the electroretinogram.

PMID- 8577451
TI  - Influence on lenticular glutathione research.
AB  - Otto Hockwin influenced the early research career in ophthalmic biochemistry of
      William Rathbun in several ways. These included multiple exposures via symposia
      to the European research community, providing editorial experience and
      encouragement to expand fundamental glutathione enzyme research to the problems
      of aging, species variation and anti-cataract drug development.

PMID- 8577452
TI  - The blood-aqueous barrier in eyes with pseudoexfoliation syndrome.
AB  - Eyes with pseudoexfoliation syndrome (PEX) frequently show clinical signs of
      impairment of the blood-aqueous barrier. Herein we give an overview of recent
      studies that analyzed the blood-aqueous barrier in eyes with PEX. METHODS: The
      authors review and summarize recent studies including quantification of aqueous
      flare in eyes with PEX using the laser flare cell meter (LFCM; Kowa FC-1000) in
      comparison with normal eyes and eyes with primary open-angle glaucoma (POAG),
      quantification of aqueous flare in eyes with PEX with and without secondary open
      angle glaucoma (SOAG), and quantitative biochemical determination of total
      aqueous protein concentration in PEX eyes. In addition, studies of noninvasive
      quantification of the blood-aqueous barrier breakdown following trabeculectomy
      and following phacoemulsification with intraocular lens implantation in eyes with
      and without PEX are reviewed. RESULTS: In eyes with manifest PEX, both aqueous
      flare and aqueous protein concentration were significantly increased in
      comparison with normal control eyes and eyes with POAG. Flare values in PEX eyes
      with SOAG were not significantly different from flare values in PEX eyes without
      SOAG. Following trabeculectomy as well as following cataract surgery, breakdown
      of the blood-aqueous barrier as determined by quantification of aqueous flare was
      significantly higher in eyes with PEX than in eyes without PEX. CONCLUSIONS:
      Impairment of the blood-aqueous barrier with increase in aqueous protein
      concentration is a feature of PEX and may be quantified both by flare measurement
      and by biochemical protein determination. The extensive blood-aqueous barrier
      breakdown in eyes with PEX following intraocular surgery is an important risk
      factor for early or late postoperative complications. The alterations of the
      blood-aqueous barrier should be considered in the medical and surgical treatment
      of eyes with PEX.

PMID- 8577453
TI  - Free radicals and aging of anterior segment tissues of the eye: a hypothesis.
AB  - A hypothesis is proposed that aging processes in the eye occur as a consequence
      of degradation of enzymes that normally metabolize and detoxify hydrogen peroxide
      and other free radicals. The loss of enzyme activity allows hydrogen peroxide,
      which normally occurs within eye fluids, and free radicals to induce irreversible
      deleterious effects on different eye tissues. These processes may lead to
      cataract formation in the lens, loss of corneal endothelial cells, modification
      of the glycosaminoglycan secretory patterns of the cells of the trabecular
      meshwork, and other changes associated with ocular aging. These processes may be
      exacerbated during inflammation when oxidation products increase. Considerable
      circumstantial evidence points towards hydrogen peroxide as one of the major
      chemicals involved in the induction of these changes. Much remains to be
      determined to definitively identify this chemical or free radicals as the primary
      inducers of tissue alterations that occur in aging eyes.

PMID- 8577454
TI  - Retinal pigment epithelium cell culture as a model for evaluation of the toxicity
      of tamoxifen and chloroquine.
AB  - The retinal pigment epithelium (RPE) removes the outer segments of photoreceptor
      cells by phagocytosis. We studied the effects of tamoxifen and chloroquine on the
      activity of the lysosomal enzymes N-acetyl-beta-glucosaminidase and cathepsin D
      in RPE in vitro to evaluate the possible eye toxicity caused by these drugs. The
      results show decreases in the activities of lysosomal enzymes after drug
      exposure. The enzymes tested seemed to be more sensitive to tamoxifen than to
      chloroquine. A profound decrease in the activities of the lysosomal enzymes only
      started at concentrations above therapeutic dose levels.

PMID- 8577455
TI  - Changes in the aging rat retina.
AB  - To characterize aging as a factor responsible for structural changes, the retinae
      of 47 Wistar-derived albino rats and 50 pigmented rats of the Norway and BDE
      (Han) strains between the ages of 1 and 36 months were examined by light and
      electron microscopy and analyzed for changes in cell densities. In all 3 rats
      strains there was an overall decline in nuclear densities of outer layer nuclei
      by 38-50% and inner layer nuclei by 27-33% between the ages of 1 and 27 months.
      Over the same age range, the ganglion cell loss was comparable to the decline in
      the inner nuclear layer. Neuronal cell death occurred at all ages and was more
      pronounced in albino rats. Moreover, in albino rats, cones were more resistant
      than rods to destruction by age and ambient light. As age-related ultrastructural
      changes in the retinal pigment epithelium (RPE) (1) a substantial accumulation of
      lipofuscin; (2) an apparent thickening of the basement membrane; (3) greatly
      enlarged and pleomorphic basal infoldings, and (4) shorter apical microvilli were
      encountered. Besides mature stage IV melanosomes 27-month-old BDE (Han) and 36
      month-old Norway rats also revealed stage III melanosomes. Tyrosinase activity in
      peripheral RPE cells could be demonstrated in Norway rats up to 12 months old and
      BDE (Han) rats up to 24 months old. Characteristics of RPE cells in old rats of
      these two pigmented strains were also melanolysosomes, melanophagolysosomes and
      melanolipofuscin granules. Age-related changes in retinal vessels were found in
      the superficial and deep capillary network and consisted of a 2- to 3-fold
      increase in thickness of the capillary basement membrane.

PMID- 8577456
TI  - Common pathways in lens research.

PMID- 8577457
TI  - The use of Scheimpflug photography in the documentation of clinical states and in
      the biometry of the anterior eye segment.
AB  - From the start of our collaboration with the Institut fur Experimentelle
      Ophthalmologie in the early 1980s, the scientist Otto Hockwin has always taken
      the greatest interest in the clinical use of Scheimpflug photography. I became a
      student of Hockwin's through my work on the effects of Verapramil. The
      straightforwardness and purposeful approach with which Hockwin persued any
      subject, once he had taken it up, served me as example and thereby helped me
      repeatedly to regain courage and patience in my own work. The Scheimpflug
      apparatus developed by Hockwin's team has proven its superiority over the
      conventional slit lamp photography through its excellent depth of focus. Further
      to the clinical applications of the Scheimpflug photography worked out by us and
      summed up once again in this paper, it also presents a widening of the scope
      hence available within ophthalmological teaching methods, which we can hardly do
      without these days. The students benefit from the far superior spatial image
      conveyed by the optical section through the anterior eye segment, compared to
      that obtained by the conventional slit lamp photography alone. The precision of
      the reproducible image of the anterior segment furthermore represents a vital
      supplementary aid in the solution of pre- and postoperative, as well as
      specialist diagnostic problems.

PMID- 8577458
TI  - Topographic distribution of prednisolone in the lens after organ culture.
AB  - Topographic distribution of prednisolone in the lens after organ culture was
      investigated. Freshly enucleated pig lenses were divided into two groups; the
      complete vitreous was removed from the lenses in group A, and the adherent parts
      of the vitreous were left in group B. Groups A and B were each divided into two
      subgroups which were separated according to drug application: two groups
      underwent drug application by a divided chamber (Iwata, 1982, DC) and two groups
      by a closed chamber. The incubation medium was TCM-199 with 2 micrograms/ml
      prednisolone, and the incubation was performed for 8 h. In order to know the
      participation of the vitreous in drug penetration into the lens, prednisolone was
      applied by a divided chamber from the anterior or posterior side, with or without
      vitreous, and incubated for 4 h as a first incubation. A secondary incubation was
      performed for another 4 h with a medium that did not contain prednisolone. After
      the lens incubation, the lenses were separated into single lens layers, and the
      drug concentration of each lens layer was measured by high performance liquid
      chromatography. The highest prednisolone concentration in the lens was detected
      by a closed chamber in the equatorial part followed by the posterior cortex,
      anterior cortex and nucleus. There were no significant differences in drug
      concentration due to the direction of drug application or the absence or presence
      of vitreous. The prednisolone distribution pattern in the lens by DC depended on
      the direction from which the drug was applied. The highest drug concentrations
      were detected in the lens cortex of the drug-applied side followed by the
      equator. No drug was detected in the side of the lens opposite the drug-applied
      side or in the nucleus. When a drug was applied from the posterior lens side, the
      presence of the vitreous made a big difference in the amount of drug penetration.
      The comparison of drug concentration between the absence or presence of the
      vitreous after secondary incubation in a medium that did not contain prednisolone
      indicated that the vitreous participates in the drug kinetics of the lens. The
      experiments suggest that while prednisolone penetration into the posterior lens
      part is small compared to that of the anterior part, when the steroid penetrated
      into the posterior part it remained there for a long period.

PMID- 8577459
TI  - A 40 years crusade through the universe of lens research.

PMID- 8577460
TI  - A mild progression type of naphthalene-induced cataract in brown-Norway rats.
AB  - Naphthalene-induced rat cataract is a useful experimental cataract--however,
      because of its short survival period, studies using this model have been for
      limited purposes. Based on the consideration that the short survival might be
      caused by systemic toxicity of an overdose of naphthalene administration (1 g/kg
      body weight every other day), the authors successfully established a naphthalene
      induced cataract with mild progression in Brown-Norway rats. The naphthalene
      administration proposed is to initially administer 0.5 g/kg and after a 1-week
      interval 1 g/kg of 10% naphthalene once or twice a week through a stomach tube.
      While the type of lens opacification induced in the two groups administered once
      and twice a week, respectively, was the same as that seen by the previous
      administration method, the progression of lens opacification seen in the groups
      showed a dose-dependent increase. The survival rate in the rats given naphthalene
      every other day according to the old method was 50% at the 6th week and 0% at the
      9th week. Survival of the two new groups was 70 and 60% at the 30th week,
      respectively. This new type of naphthalene-induced rat cataract should be a
      suitable model for long-term observations.

PMID- 8577461
TI  - H2O2 determination in rat lens: chemiluminescent versus radioisotopic methods.
AB  - Hydrogen peroxide levels have been determined in rat lenses by using two methods,
      a chemiluminescent and a radioisotopic method. The average content was found to
      be 155 +/- 20 and 127 +/- 18 nmol/g wet weight of the tissue, respectively, by
      the two methods. The reaction of H2O2 with dichlorophenol-indophenol in the
      presence of peroxidase was also studied. However, this was found to be less
      suitable. The results of the chemiluminescent determinations are similar to the
      results with the radioisotopic methods demonstrating the feasibility of
      determining H2O2 by chemiluminescence measurement as well.

PMID- 8577462
TI  - Basic biochemical parameters of one hundred cataractous lenses from Egyptian
      patients.
AB  - Cataractous lenses from an extended population of 100 Egyptian patients whose
      age, sex and case history had been recorded, were collected and classified
      morphologically. After determination of the lens wet weights, lenses were
      microsectioned and basic parameters such as wet weight, dry weight, water content
      and contents of water-soluble and water-insoluble crystallins of the samples were
      determined. The data obtained document moderate as well as drastic changes of the
      investigated parameters along with aging and cataractogenesis, and extend our
      knowledge from small numbers of hitherto investigated human lenses to a
      considerably high number of cases.

PMID- 8577463
TI  - Distribution of water-soluble crystallins in microsectioned cataractous lenses
      from one hundred Egyptian patients.
AB  - Morphologically classified lenses from 100 cataract patients from the Mansoura
      Eye Hospital (Egypt) were microdissected and the crystallin composition and
      distribution were analyzed by thin-layer isoelectric focusing (IEF). The IEF
      profiles of cataractous lenses were compared with each other, with those of
      sclerotic lenses and with a normal lens profile. The alterations in the
      composition of high-molecular-weight (HMW)-, alpha-, beta H-, beta L-, beta s-,
      and gamma-crystallins along with normal aging, are superimposed by pronounced
      cataract-related changes which are different for the various types of cataracts.
      The general feature includes a continuous loss of gamma-, beta s- and beta L
      crystallins of higher IEPs and an increase of HMW material. This is highly
      pronounced in the nucleus of nuclear cataractous lenses. In cortical cataractous
      lenses, changes start in the cortical layers. No differences could be observed
      between alterations in Caucasian lenses and this extended Egyptian lens
      population.

PMID- 8577464
TI  - Effects of UV-B on the growth pattern of bovine passage I and II lens epithelial
      cells in vitro.
AB  - To further evaluate the pivotal role of epithelial cell proliferation in lens
      homeostasis, this study compares the principles of regional growth control in
      central and preequatorial bovine lens epithelial cells in culture. Central lens
      epithelial cells do not proliferate in vivo while preequatorial cells do. In
      tissue culture, both central and preequatorial cells proliferate, albeit at
      different rates. At all stages investigated, nonirradiated passage I central
      cells proliferated less extensively when compared to the preequatorial cells. In
      contrast, central passage II cells showed a higher proliferation rate than
      peripheral cells until day 7, when the situation reversed. UV-B radiation led to
      a dose-dependent reduction of cell proliferation but did not change the principle
      cytokinetic differences between central and peripheral cells in passage I cells.
      Under all circumstances, passage I cells grew more intensively than their passage
      II counterparts. Data on origin-related differences in cell proliferation of
      cultured lens epithelial cells suggests growth control features other than just
      the regionally limited expression of growth factor receptors in the preequatorial
      extracellular matrix and cell membranes. Investigations are seen as an important
      step towards a better understanding of the features underlying regional
      proliferation control and its impairments, at least in lens epithelial cells.

PMID- 8577465
TI  - Simultaneous measurement of reduced and oxidized glutathione in human aqueous
      humor and cataracts by electrochemical detection.
AB  - A sensitive, electrochemical method was employed for the simultaneous measurement
      of reduced and oxidized glutathione in lens cortex, nucleus and capsule epithelia
      of rabbit lenses, normal human lenses and human cataracts. In addition, aqueous
      humor from cataract patients was also analyzed. The level of GSSG in the nucleus
      of human cataracts was significantly higher than that in the nucleus of normal
      eye bank lenses. The capsule epithelium of intracapsular extracted cataracts
      possessed high levels of reduced glutathione, despite the fact that much of the
      glutathione in the cortex and nucleus of the lenses was depleted. Levels of GSH
      in the aqueous humor of cataract patients were several times higher than those
      reported for normal aqueous humor. Electrochemical detection proved to be a
      useful technique for analysis of reduced and oxidized glutathione in lens and
      aqueous humor, especially when sample size is small, such as for capsule
      epithelium.

PMID- 8577466
TI  - Maturation of fiber membranes in the human eye lens. Ultrastructural and Raman
      microspectroscopic observations.
AB  - Electron microscopic, freeze fracture and cholesterol cytochemical studies have
      revealed that the maturation of lens fibers is accompanied by considerable
      changes in the ultrastructure of their limiting membranes. These changes are in
      line with biochemical studies on the cholesterol content in the lens and support
      the physiological notion that upon maturation lens membranes are transformed from
      normal permeable to nonleaky membranes. In addition it is shown that early
      cortical changes involved disturbances of lens membranes. As a consequence it can
      be postulated that, in order to be significant, future studies on the early
      events leading to cataractous disturbances must be carried out using a
      combination of histochemical, immunohistochemical and regional biochemical
      approaches.

PMID- 8577467
TI  - Ten years of cataract epidemiology studies in the Department of Experimental
      Ophthalmology, 1980-1990.
AB  - The knowledge of the multifactorial genesis of the so-called senile cataract has
      initiated an intensified search for cataract-related risk factors. The mechanisms
      of syn- and cocataractogenesis could already be shown in the Department of
      Experimental Ophthalmology, Bonn, in the seventies. Subsequently, cataract
      epidemiology became a field of interest in 1980 when all available
      epidemiological data related to cataract research were first collected and
      reviewed. It has become obvious that the various types of cataract morphology do
      not represent one unique disease 'senile cataract' but reflect different
      biochemical characteristics. A preliminary study assigned data of case history as
      well as blood and lens biochemistry to four types of lens opacity. Scheimpflug
      photography and multilinear microdensitometry were the basis for classifying
      cataract lenses. After increasing the number of involved patients, the data were
      analyzed by means of multivariate statistics. The originally used cataract
      classification system was enlarged to eight types of frequently seen cataract
      morphologies. A control group was built up to enable case-control studies as well
      as to obtain characteristics of normal lens density related to age.

PMID- 8577468
TI  - Evaluation of lens transparency changes through photographed images during a 13
      month observation period.
AB  - Since the development of the anterior eye segment analysis system, several new
      types of anterior eye segment biometry have been performed. The main aim of this
      study was to evaluate whether changes in cataractous progression or an increase
      in lens transparency loss are detectable during a relatively short period of 13
      months by measuring the intrapupillary opaque shadow area through
      retroillumination images or by calculating the light scattering intensity at the
      deepest cortical layer of the lens through Scheimpflug slit images. Secondly, the
      relationship between maximally dilated pupil sizes and patients' ages and that
      between cases with and without diabetes were studied. Thirty-one eyes (49.2%) of
      sixty-three cataractous lenses showed more than 5% increase in the opaque shadow
      area. Forty-five eyes (60.0%) showed more than a 5% increase in light scattering
      intensity. 92.5% of diabetic eyes and 92.3% of nondiabetic eyes showed pupil
      sizes over 6.5 mm after an instillation of mydriatica. In our study the applied
      method guaranteed a high reproducibility; thus is might be possible to detect an
      increase in cataractous changes and lens transparancy in around 50% of examined
      subjects in a period as short a 1 year. For the evaluation of cataract
      progression through a retroillumination image, the recommendable pupil size is >
      or = 6.5 mm.

PMID- 8577469
TI  - Computed tomographic images and three-dimensional expression of crystalline lens
      findings from multiple slices of Scheimpflug slit images.
AB  - Although the observation of lens changes in clinical examination has been made
      through a slit lamp microscope under dilated pupil, precise documentation and
      analysis of lens changes are presently possible through Scheimpflug photographic
      images. However, the methodology is still unsatisfactory because the image
      analysis is two dimensional. In order to overcome this disadvantage, the authors
      aimed at developing a new methodology for obtaining computed tomographic images
      of the lens. 60 Scheimpflug slit images of a cataractous human lens were taken by
      an anterior eye segment analysis system as digital data. After the locations of
      the whole slit images had been matched, reconstruction of the coronal section
      line images was performed utilizing extracted image information. The total number
      of reconstructed coronal section images in additional procedures of the image
      interpolation was 150. Computed tomography of the lens image was made from those
      150 images. A whole lens figure was also demonstrated as a moving three
      dimensional image.

PMID- 8577470
TI  - [... Organ donation must remain a donation].

PMID- 8577471
TI  - [Alternatives to geriatric care in the hospital].

PMID- 8577472
TI  - [Nursing and care of the brain-dead patient until organ removal].

PMID- 8577473
TI  - [A shady side of nursing...].

PMID- 8577474
TI  - [Transplantation--yes or no? An ethical-psychological discussion about it by one
      to whom it happened].

PMID- 8577475
TI  - [Nursing at home rather than in the hospital. A model trial by Merkur and the Red
      Cross].

PMID- 8577476
TI  - [New forms of ambulatory performance in health care delivery].

PMID- 8577477
TI  - [Meeting of the International Council of Representatives in Harare].

PMID- 8577478
TI  - Noradrenaline-evoked pain in neuralgia.

PMID- 8577479
TI  - Increased cerebrospinal fluid Met-enkephalin immunoreactivity in patients with
      chronic tension-type headache.
AB  - Cerebrospinal fluid (CSF) concentration of Met-enkephalin immunoreactivity (Met
      enkephalin-ir) was determined by radioimmunoassay in 47 patients with chronic
      tension-type headache and in 47 headache-free control subjects. Thirty-nine of
      the controls were patients receiving spinal analgesia before surgery for diseases
      not associated with pain; 8 were healthy paid volunteers. Patients reporting
      migraine more than 1 day per month were excluded. Pericranial tenderness,
      nociceptive flexion reflex and thermal pain thresholds were determined in the
      majority of the patients. The median level of CSF Met-enkephalin-ir was
      significantly higher (115 pmol/l) (quartiles (107-134) pmol/l) in the headache
      patients than in the controls (median 79 pmol/l) (quartiles (73-87) pmol/l) (Mann
      Whitney, P < 0.001). No indication of sex-difference or correlation with age with
      respect to CSF Met-enkephalin-ir was found. No correlation was found between CSF
      Met-enkephalin-ir and either pericranial tenderness, nociceptive flexion-reflex
      threshold, or thermal pain threshold. There was no indication of correlation
      between consumption of mild analgesics and CSF Met-enkephalin-ir. The higher
      levels of CSF Met-enkephalin-ir in the headache patients may be indicate
      activation of the enkephalinergic antinociceptive system at the spinal/trigeminal
      level, whereas the beta-endorphinergic system appears normal. This
      enkephalinergic activation may be caused by increased activity in the primary
      nociceptive afferents, or may be compensatory to decreased activity in other
      endogenous antinociceptive systems than the opioid.

PMID- 8577480
TI  - Peripheral administration of nerve growth factor in the adult rat produces a
      thermal hyperalgesia that requires the presence of sympathetic post-ganglionic
      neurones.
AB  - Previous evidence suggests that, in adult animals, nerve growth factor (NGF) can
      induce hyperalgesia, and may be an endogenous mediator in some persistent pain
      states. Here we have studied the effects of single intradermal injections of 50
      500 ng of human recombinant NGF into the plantar skin of adult rat hindpaws. We
      found that doses of 250 ng and more produced a prolonged and stable thermal
      hyperalgesia to radiant heat. NGF did not produce overt pain behaviour as judged
      by the absence of paw licking or guarding of the injected paw. In animals
      subjected to surgical or chemical sympathectomy, by repeated systemic
      guanethidine treatments, the hyperalgesic effects of NGF were markedly reduced.
      We also found that NGF produced plasma extravasation in rat skin, using the
      Evan's blue method, with a dose dependency similar to that determined for
      hyperalgesia. Together, these findings suggest that NGF can lead to a rapid
      activation and sensitization of cutaneous nociceptors. However, these actions
      appear at least partly indirect, requiring the presence of normal sympathetic
      post-ganglionic terminals.

PMID- 8577481
TI  - Noradrenaline-evoked pain in neuralgia.
AB  - We have tested the effects of cutaneous application of noradrenaline in 35
      patients presenting with neuropathic pain. Depending on the outcome of
      sympatholytic interventions the patients were considered to have sympathetically
      maintained pain (SMP; n = 25) or sympathetically independent pain (SIP; n = 10).
      Iontophoretic application or cutaneous injection of noradrenaline into
      symptomatic skin aggravated pain and mechanical or thermal hyperalgesia in 7/25
      SMP patients. Results from differential nerve blocks suggested that noradrenaline
      induced ongoing pain and heat hyperalgesia were signalled by unmyelinated
      afferents, while touch-evoked pain and cold hyperalgesia were signalled by
      myelinated afferents. In none of the remaining 18/25 SMP patients, 10 SIP
      patients or 18 normal subjects did application of noradrenaline result in any
      appreciable increase of pain. A follow-up of 12 patients (initially 9 SMP, 3 SIP)
      after 12-16 years showed that one individual (previously SMP) was healthy, while
      3 patients still suffered from SMP and 8 from SIP. Of the 5 SMP patients who had
      noradrenaline-induced pain at the initial examination, only 1 SMP patient still
      responded to noradrenaline with pain and hyperalgesia. Three other patients had
      changed to SIP and 1 individual was healthy. None of these 4 and none of the 7
      initially noradrenaline-unresponsive patients experienced pain to the
      noradrenaline challenge at follow-up. Thus, cutaneous noradrenaline application
      can aggravate the pain in some, but not all SMP patients. THe abnormal
      noradrenaline reaction can change over time as can the pain relieving effects of
      sympatholytic therapy.

PMID- 8577482
TI  - Phrenic afferent input excites C1-C2 spinal neurons in rats.
AB  - Effects of electrical stimulation of the ipsilateral phrenic nerve above the
      heart were determined on cells in the C1-C2 spinal cord segments of 27 rats
      anesthetized with pentobarbital. Forty-five cells that responded to this stimulus
      were included in this study. These cells then were examined at the same stimulus
      parameters for effects of stimulating the ipsilateral phrenic nerve below the
      heart, the contralateral phrenic nerve above the heart, and/or the left
      (ipsilateral) cervical vagus nerve. Ipsilateral phrenic nerve stimulation below
      the heart had no effect on 20 of 20 cells tested. Seven of 16 cells tested for
      effects of contralateral phrenic nerve stimulation above the heart were excited
      and activity of 9 cells was unaffected. Activity changes and activation latencies
      were not significantly different in the 7 cells excited by both ipsilateral and
      contralateral phrenic nerve stimulation. Thirty-seven of 45 cells excited by
      ipsilateral phrenic nerve stimulation also were excited by stimulation of the
      left cervical (ipsilateral) vagus nerve. The mean increase in cell activity was
      significantly greater following vagal nerve stimulation compared to phrenic nerve
      stimulation, and mean activation latency was significantly longer for vagal
      stimulation. Excitatory receptive somatic fields were classified for 35 cells.
      Somatic field locations for most cells (80%) included the ipsilateral neck and
      jaw. Activity of 26 cells was increased by both noxious pinch and brushing the
      hair, activity of 6 cells was increased only by noxious pinch, and activity of 3
      cells was increased only by brushing the hair. Results of this study indicate
      that there are afferent fibers in the phrenic nerve above the heart, but not
      below the heart, that excite cells in the C1-C2 segments of the spinal cord. Most
      cells also were excited by noxious stimuli applied to their somatic receptive
      fields. Thus, the phrenic nerve may provide a pathway for referral of pain to the
      neck and jaw from thoracic structures.

PMID- 8577483
TI  - Reflex sympathetic dystrophy: changing concepts and taxonomy.
AB  - We present a revised taxonomic system for disorders previously called reflex
      sympathetic dystrophy (RSD) and causalgia. The system resulted from a special
      consensus conference that was convened on this topic and is based upon the
      patient's history, presenting symptoms, and findings at the time of diagnosis.
      The disorders are grouped under the umbrella term CRPS: complex regional pain
      syndrome. This overall term, CRPS, requires the presence of regional pain and
      sensory changes following a noxious event. Further, the pain is associated with
      findings such as abnormal skin color, temperature change, abnormal sudomotor
      activity, or edema. The combination of these findings exceeds their expected
      magnitude in response to known physical damage during and following the inciting
      event. Two types of CRPS have been recognized: type I, corresponds to RSD and
      occurs without a definable nerve lesion, and type II, formerly called causalgia
      refers to cases where a definable nerve lesion is present. The term
      sympathetically maintained pain (SMP) was also evaluated and considered to be a
      variable phenomenon associated with a variety of disorders, including CRPS types
      I and II. These revised categories have been included in the 2nd edition of the
      IASP Classification of Chronic Pain Syndromes.

PMID- 8577484
TI  - Comments on Fitzgibbon and Galer, PAIN, 58 (1994) 429-431.

PMID- 8577485
TI  - Avoiding fallacies in nociceptive measurements.

PMID- 8577486
TI  - Changes in neuronal markers in a mononeuropathic rat model relationship between
      neuropeptide Y, pre-emptive drug treatment and long-term mechanical hyperalgesia.
AB  - Using the chronic constriction model (CCI) of Bennett and Xie (1988), changes in
      the lumbar spinal cord in neuropeptides and lectin IB4 were examined at 28 days
      post-nerve constriction and were compared with the degree of mechanical
      hyperalgesia. Animals following nerve ligation were significantly more
      hyperalgesic than sham-operated animals (P < 0.0001). Lectin IB4, a marker of
      primary afferent C fibres, showed a qualitative decrease in staining intensity in
      laminae 1-2 with ligation compared with both the unoperated contralateral side
      and with sham animals. Using fluorescent immunohistochemistry to quantify changes
      in neuropeptides in the dorsal horn we found that substance P showed significant
      decreases with ligation compared to sham operation (P < 0.002). CGRP and galanin
      showed no significant changes in laminae 1-2 compared to sham-operated animals.
      Neuropeptide Y (NPY) showed no significant changes in intensity in laminae 1-2;
      however, in laminae 3-4 there was a significant increase with nerve ligation
      compared to sham (P < 0.005). We examined how pre-emptive drug treatment affected
      these neuronal markers at 28 days. We used (1) clonidine, an alpha 2
      adrenoreceptor agonist (1 mg/kg, i.p.), (2) morphine, a mu-opioid agonist (5
      mg/kg, i.p.) or (3) MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist
      (0.3 mg/kg, s.c.) administered 30 min prior and 6 h following nerve ligation or
      sham-operation. Hyperalgesia in the ligated group at 28 days was suppressed by
      treatment with pre-emptive clonidine (P = 0.003) or MK-801 (P = 0.003) but not
      morphine. With the exception of NPY there was no effect of pre-emptive drug
      treatment on any neuronal marker examined. Pre-emptive MK-801 reduced the
      magnitude of the increase in NPY in laminae 3-4 in the ligated group (P < 0.005)
      and clonidine showed a similar trend but this did not reach significance.
      Morphine had no effect on NPY staining. There was a significant correlation
      between the increase in NPY staining in laminae 3-4 and the degree of
      hyperalgesia (r = 0.6, P < 0.001). These results suggest that the increased NPY
      expression in laminae 3-4 of the spinal cord (the territory of the myelinated
      sensory input) may be crucial to the development of hyperalgesia in this model.

PMID- 8577487
TI  - The attentional control of pain: methodological and theoretical concerns.
AB  - Although it is now well accepted that attention-based cognitive coping strategies
      are effective in altering pain perception and have potentially useful analgesic
      qualities, there exists contradiction and equivocation as to the role of various
      factors in the production of that analgesia. Cioffi (1991) has suggested that the
      response to this equivocation has been a 'collective ennui' on the part of
      researchers. This article seeks to explore methodological and theoretical reasons
      for this reigning equivocation and offers some suggestions for moving beyond it.
      In particular, critical attention is focussed upon four possible sources of
      variance in experimental pain procedures: the choice of the pain induction
      procedure, the instructions given, the measures taken and the content of the
      taught strategy.

PMID- 8577488
TI  - Effect of lamotrigine in the acute and chronic hyperalgesia induced by PGE2 and
      in the chronic hyperalgesia in rats with streptozotocin-induced diabetes.
AB  - There is still a need for a new analgesic devoid of the side effects presented by
      opioids or non-steroidal anti-inflammatory drugs, for the treatment of some acute
      and chronic pain conditions. Lamotrigine (Lamictal1, 10-100 mg/kg), a new
      anticonvulsant, showed analgesic effects in the acute model of prostaglandin E2
      (PGE2)-induced hyperalgesia when given orally before or after the subplantar
      injection of PGE2 in the rat. It also inhibited the development of sustained
      hyperalgesia induced by multiple subplantar injections of PGE2 when administered
      orally prior to the PGE2 injections. Furthermore, lamotrigine induced analgesia
      in the model of chronic hyperalgesia in streptozotocin-induced diabetic rats. The
      effects of carbamazepine and phenytoin are compared to the effects of lamotrigine
      in this model. The results suggest that lamotrigine could be used in pain
      conditions where neuronal sensitization may be present and possibly also where it
      could inhibit the development of this sensitization.

PMID- 8577489
TI  - Spinal mu and delta, but not kappa, opioid-receptor agonists attenuate responses
      to noxious colorectal distension in the rat.
AB  - The antinociceptive efficacy of different opioid-receptor agonists following
      their intrathecal (i.t.) administration was examined in awake, unanesthetized
      rats in a model of visceral pain. Cumulative i.t. doses of the mu-preferring
      opioid-receptor agonist morphine produced dose-dependent attenuation of the
      change (increase) in mean arterial pressure (delta MAP) and elevation of the
      visceromotor threshold to colorectal distension (CRD). Similar dose-dependent
      antinociceptive effects were produced after i.t. administration of the mu opioid
      receptor-selective agonist DAMPGO. Morphine and DAMPGO were equipotent against
      the delta MAP to phasic CRD (80 mm Hg, 20 sec), but DAMPGO was more than 6 times
      more potent than morphine in elevating the visceromotor threshold to an
      incrementing CRD. Intrathecal administration of the delta opioid-receptor
      selective agonist DPDPE produced, like morphine and DAMPGO, a dose-dependent
      attenuation of the delta MAP to CRD; DPDPE was one-tenth as potent as morphine or
      DAMPGO. DPDPE also dose-dependently elevated the visceromotor threshold to CRD,
      but its efficacy was only half that of morphine or DAMPGO. The kappa opioid
      receptor-selective agonist U 50488H was without antinociceptive efficacy after
      i.t. administration, but did attenuate responses to CRD after systemic
      administration. The antinociceptive effects produced by morphine and DAMPGO were
      antagonized by i.t. pretreatment with naloxone and the effects produced by DPDPE
      were antagonized by i.t. pretreatment with the delta opioid-receptor-selective
      antagonist naltrindole. These data indicate that local mu and delta, but not
      kappa, opioid receptors can modulate visceral nociceptive transmission in the
      spinal cord.

PMID- 8577490
TI  - Disruption and restoration of dorsal horn sensory map after peripheral nerve
      crush and regeneration.
AB  - Formalin injection into the hindpaw of rats produces many neurons with c-fos
      protein-like immunoreactivity (fos-neurons) in the medial 3/4 of the ipsilateral
      dorsal horn laminae I and II at the junction of 4th and 5th lumbar segments (the
      sciatic territory). The tibial nerve transection 2 or 3 days earlier resulted in
      almost complete elimination of stimulation-induced fos-neurons in the tibial
      territory (medial 1/2 of the sciatic territory). When the animals had been
      conditioned by crushing the tibial nerve 2 weeks before stimulation (11 or 12
      days before transection), the number of fos-neurons significantly increased
      compared to simple transection alone. The increase (2.5-fold) was greatest in the
      tibial territory. Therefore, the dorsal horn neurons in the deafferented tibial
      territory exhibited hypersensitivity to intact peroneal primary input, and the
      somatotopy map was disrupted. When the nerve had been crushed 3 weeks (18 or 19
      days earlier than transection) rather than 2 weeks before stimulation, however,
      the number and distribution of fos-neurons were not different from those without
      conditioning (transection alone). Regenerated tibial nerve fibers were capable of
      transganglionic transport of WGA-HRP from the hindpaw receptive field to the
      tibial territory of the dorsal horn by 3 weeks but not by 2 weeks following the
      nerve crush. When transection was omitted, noxious signal transmitted through the
      tibial nerve fibers regenerated by 3 weeks after crush was capable of inducing c
      fos in the tibial territory. The injury-induced hypersensitivity of dorsal horn
      neurons and resulting disruption of somatotopy map were reversed by re
      establishment of peripheral tissue-nerve interaction.

PMID- 8577491
TI  - Unilateral decrease in thalamic activity observed with positron emission
      tomography in patients with chronic neuropathic pain.
AB  - The oxygen-15 water bolus positron emission tomography (PET) method was used to
      image regional brain activity in 4 patients with chronic post-traumatic
      neuropathic pain confined to one lower limb and in 1 patient with post-herpetic
      neuralgia. In comparison to 13 normal subjects, scans of the patients disclosed a
      statistically significant decrease in thalamic activity contralateral to the
      symptomatic side. Examination of the right/left ratio for all the subjects showed
      that the values for the patients fell at the extremes of the normal range,
      according to the side of the affected body part. These initial observations
      suggest that functional alterations in thalamic pain processing circuits may be
      an important component of chronic neuropathic pain.

PMID- 8577492
TI  - Validation of World Health Organization Guidelines for cancer pain relief: a 10
      year prospective study.
AB  - This paper reports on the experience gained using World Health Organization
      Guidelines for cancer pain relief over a 10-year period in an anaesthesiology
      based pain service associated with a palliative care programme. The course of
      treatment of 2118 patients was assessed prospectively over a period of 140,478
      treatment days. Non-opioid analgesics (WHO step I) were used on 11%, weak opioids
      (WHO step II) on 31% and strong opioids (WHO step III) on 49% of treatment days.
      Administration was via the enteral route on 82% and parenterally on 9% of
      treatment days. On the remaining days, either spinally applied opioids (2%) or
      other treatments (6%) were utilised. Fifty-six percent of the patients were
      treated with morphine. Morphine dose escalation was observed in about one-half of
      the patients being cared for until death, whereas the other half had stable or
      decreasing doses over the course of treatment. Co-analgesics were administered on
      37% of days, most often antidepressants (15%), anticonvulsants (13%) and
      corticosteroids (13%). Adjuvants to treat symptoms other than pain were
      prescribed on 79% of days, most commonly laxatives (42%), histamine-2-receptor
      antagonists (39%) and antiemetics (35%). In addition, palliative antineoplastic
      treatment was performed in 42%, nerve blocks in 8%, physiotherapy in 5%,
      psychotherapy in 3% and TENS in 3% of patients. A highly significant pain
      reduction was achieved within the 1st week of treatment (P < 0.001). Over the
      whole treatment period, good pain relief was reported in 76%, satisfactory
      efficacy in 12% and inadequate efficacy in 12% of patients. In the final days of
      life, 84% rated their pain as moderate or less, while 10% were unable to give a
      rating. Analgesics remained constantly effective in all 3 steps of the WHO
      ladder. Other clinical symptoms were likewise significantly reduced at 1 week
      after initial assessment, with the exception of neuropsychiatric symptoms. During
      the course of treatment, the latter were the major symptoms on 23% of days,
      followed by nausea (23%), constipation (23%) and anorexia (20%). Our results
      emphasise once again the marked efficacy and low rate of complications associated
      with oral and parenteral analgesic therapy as the mainstay of pain treatment in
      the palliative care of patients with advanced cancer. Wide dissemination of WHO
      guidelines among doctors and healthcare workers is thus necessary to effect a
      clear improvement in the treatment of the many patients suffering from cancer
      pain in the clinical and home setting.

PMID- 8577493
TI  - Development and initial validation of a scale to measure self-efficacy beliefs in
      patients with chronic pain.
AB  - The present study describes the development of the Chronic Pain Self-Efficacy
      Scale (CPSS), a 22-item questionnaire designed to measure chronic pain patients'
      perceived self-efficacy to cope with the consequences of chronic pain. The CPSS
      and other measures of psychosocial functioning were administered to 141
      consecutive patients who were referred to an outpatient multidisciplinary pain
      treatment program. An exploratory factor analysis of the CPSS responses
      identified 3 factors: self-efficacy for pain management (PSE), self-efficacy for
      coping with symptoms (CSE), and self-efficacy for physical function (FSE). The
      CPSS then was administered to a replication sample of 136 chronic pain patients.
      Factor analysis confirmed the 3-factor structure of the CPSS. The subscale scores
      derived from the factor analysis were significantly correlated with measures of
      depression, hopelessness, somatic preoccupation, and adaptation to the chronic
      pain experience. Multiple regression analyses provided further support for the
      concurrent and construct validity of the CPSS. The scale may aid in the
      evaluation of the self-efficacy beliefs of chronic pain patients.

PMID- 8577494
TI  - Ultrasound therapy in musculoskeletal disorders: a meta-analysis.
AB  - We have reviewed 293 papers published since 1950 to assess the evidence of effect
      of ultrasound in the treatment of musculoskeletal disorders. Twenty-two clinical
      papers describing trials comparing ultrasound treatment with sham-ultrasound
      treated, non-ultrasound treatment and untreated groups were found. These papers
      were evaluated with respect to a list of criteria which should be met in this
      type of trial. They were generally found lacking with respect to description of
      drop-outs, randomisation methods, ultrasound apparatus, sham-ultrasound
      apparatus, control of apparatus, mode of delivery, size of sound-head, treated
      area and follow-up time. In 16 of these trials, ultrasound treatments were
      compared with sham-ultrasound and in 13 cases data were presented in a way that
      made pooling possible. Two standardized effect sizes (dd/r and dd/s) were applied
      to the results to enable evaluation of the effect of ultrasound treatment on
      pain. None of the methods (dd/r = 0.64%, confidence limits -6.7 to 7.5%; and dd/s
      = 0.24, confidence limits -0.01 to 0.49) gave evidence that pain relief could be
      achieved by ultrasound treatment. Hence we found no reason to analyze the other
      papers where ultrasound treatment was compared with another treatment or an
      untreated control group. We found a significant influence of degree of blinding
      using the d/s for the analysis (t test, P = 0.009), while when the d/r was used,
      only a trend was found (P = 0.10). An analysis of the effect of proper
      randomisation on the result was not possible because of inadequate description of
      the methods used. We conclude that the use of ultrasound in treatment of
      musculoskeletal disorders is based on empirical experience, but is lacking firm
      evidence from well-designed controlled studies. One question remaining is whether
      ultrasound treatment can augment an effect of exercise therapy with respect to
      musculoskeletal disorders.

PMID- 8577495
TI  - Capsaicin-induced flare and vasodilatation in patients with post-herpetic
      neuralgia.
AB  - The aim of the present study was to investigate the role of primary afferent
      fibres with polymodal nociceptors in the various pain symptoms and signs
      associated with post-herpetic neuralgia (PHN). Forty-four patients with PHN
      affecting thoracic dermatomes were examined clinically for evidence of sensory
      disturbance to touch and pinprick and compared to 14 normal subjects and 9
      subjects with evidence of past herpes zoster infection but no pain. The patients
      were then divided into 3 groups on the basis of their clinical symptoms and signs
      those with steady burning discomfort only (n = 12), those with burning
      discomfort, allodynia and hyperalgesia to pinprick (n = 17), and those with
      burning discomfort, allodynia and hypalgesia to pinprick (n = 15). Indirect
      measurement of primary afferent fibre function was performed by measuring the
      neurogenic axon reflex flare to topical capsaicin using Doppler flowmetry in the
      5 clinical groups. The 2 groups with allodynia had significantly decreased
      neurogenic flare responses compared to PHN subjects without allodynia and the 2
      control groups. These results suggest that allodynia in patients with post
      herpetic neuralgia may be a consequence of disrupted function of primary afferent
      fibres.

PMID- 8577496
TI  - Progression of bone lesions in a child with primary hyperoxaluria type 1:
      evaluation by roentgenology and MRI.
AB  - We report the radiological and MRI findings of bone oxalosis and their rapid and
      extensive progression in a child with primary hyperoxaluria (PH) type 1. We
      emphasize the spectrum of skeletal changes and their differences from renal
      osteodystrophy and the role played by imaging in the diagnosis and follow-up of
      oxalosis.

PMID- 8577497
TI  - Unusual radiological manifestations of Lemierre's syndrome: a case report.
AB  - Lemierre's syndrome is an uncommon clinical entity characterized by oropharyngeal
      infection followed by septic thrombophlebitis of the jugular vein with
      embolization to the lungs and other organs. The organism is a gram-negative
      anaerobic bacterium, Fusobacterium necrophorum. We report a case of Lemierre's
      syndrome in an 8-year-old child who presented with septic arthritis of the left
      hip joint. Roentgenograms and computed tomography demonstrated gas in the joint
      and adjacent soft tissues, along with a dislocated hip. Sonography of the neck
      coupled with the colour Doppler technique did not reveal any abnormality in the
      jugular veins. A blood culture grew Fusobacterium necrophorum, confirming the
      diagnosis of Lemierre's syndrome.

PMID- 8577498
TI  - Abnormal muscle MRI in a patient with systemic juvenile arthritis.
AB  - Although myositis has been described in children with systemic-onset juvenile
      arthritis (JA), its documentation by MRI has not been reported. We describe a 13
      year-old boy with systemic-onset JA, severe myalgia, and elevated muscle enzymes,
      but normal muscle strength, who had an MRI consistent with myositis. Magnetic
      resonance imaging can identify the specific location of myositis, allowing more
      precise definition of a potential complication of systemic JA.

PMID- 8577499
TI  - Pyomyositis: diagnostic value of color Doppler sonography.
AB  - The color Doppler sonographic appearance of pyomyositis and the usefulness of
      this technique in guiding needle aspiration of an intramuscular abscess in a 15
      year-old diabetic girl are described.

PMID- 8577500
TI  - Bone fractures in children undergoing orthotopic liver transplantation.
AB  - This retrospective study documents the incidence and distribution of fractures in
      117 children with end-stage liver disease who underwent orthotopic liver
      transplantation (OLT) over a 6-year period (1987-1993). Both the pre- and post
      OLT phases were included. Nineteen children (16.2 %) sustained a total of 69
      fractures. Age at time of fracture ranged from 3 months to 9 years 8 months
      (median 13.5 months). There was no documented trauma in 14/19 cases. Metabolic
      bone disease, assessed qualitatively on plain radiographs, was present in 17/19
      children at the time of fracture. This took the form of rickets (n = 3),
      osteopenia (n = 12) and osteosclerosis (n = 2). Potential risk factors including
      pre-existing metabolic bone disease, drugs and immobilization were assessed. The
      findings emphasise the need for clinical and radiological awareness of the
      fracture risk, particularly during the peri-transplant period when this risk may
      be greatest.

PMID- 8577501
TI  - Imaging of post-transplant spindle cell tumors.
AB  - Spindle/smooth muscle cell proliferation is an additional neoplastic process
      related to immunosuppression and EBV infection. We describe four post transplant
      children with this diagnosis. Multiple organ systems may be involved,
      particularly the liver, gastrointestinal tract, and lungs. Lesions are
      radiographically, clinically, and endoscopically indistinguishable from those of
      post-transplant lymphoproliferative disease (PTLD).

PMID- 8577502
TI  - Deferoxamine-induced platyspondyly in hypertransfused thalassemic patients.
AB  - Deferoxamine chelation therapy (widely used to reduce iron overload in
      hypertransfused thalassemic patients) has been implicated in causing skeletal
      growth abnormalities (rachitic-like changes in the long bones and vertebral body
      flattening), particularly when used in early infancy and at high dose levels.
      Radiographs of seven hypertransfused and well-chelated patients with thalassemia
      were reviewed. For two patients, serial films of the spine from the early 1970s
      to the present revealed a sequence of changes in the vertebral bodies, beginning
      with normal bodies that became bulbous and subsequently flattened. These two
      patients had begun deferoxamine chelation therapy early in infancy. The bone
      changes, though slightly reminiscent of post-radiation changes, are milder and
      result in a final Scheuermann-like picture.

PMID- 8577503
TI  - Magnetic resonance imaging of the shoulder in children with brachial pLexus birth
      palsy.
AB  - Five patients suffering from Erb-Duchenne brachial plexus birth palsy were
      prospectively studied with MRI. A group of 11 healthy children was used as a
      control to understand the MRI anatomy of the normal growing glenohumeral joint. A
      hypoplastic and flattened posterior part of the glenoid fossa and a blunt
      posterior labrum were found in all patients. Four patients had a blunt anterior
      labrum and a flattened humeral head. Three patients presented with a posterior
      subluxation of the humeral head. These results suggest that MRI provides a non
      ionising and non-invasive method of demonstrating the early abnormalities of the
      shoulder associated with obstetrical brachial plexus paralysis, which may prompt
      orthopaedic correction.

PMID- 8577504
TI  - The odontoid synchondrotic slip: an injury unique to young children.
AB  - We report seven children (three female, four male) diagnosed with traumatic
      synchondrotic slip of the odontoid. The clinical records, plain films and CT
      scans were evaluated retrospectively. The patients ranged in age between 3 and 5
      years. Their injuries resulted from a motor vehicle accident in four cases and
      from a fall from a height in three. The injury was isolated in five; it was
      associated with a closed head injury in one and with facial and brachial plexus
      trauma in another. Radiographs showed anterior angulation with or without
      displacement in all seven cases. Axial CT with sagittal reformation and 3D
      reconstructions were performed in six cases. This confirmed the synchondrotic
      slip and, in addition, identified a rotary component to the injury in three
      cases, with compromise of the canal in two. Other additional injuries were also
      noted. All cases were treated conservatively and the injuries healed. Only one
      child had a neurological deficit attributable to her head injury rather than her
      cervical injury (MR of the cervical cord was normal). The presence of the
      synchondrosis between the dens and the body of C-2 makes this injury unique to
      children under 7 years of age; by the age of 7 the synchondrosis has fused.

PMID- 8577506
TI  - Metachondromatosis.
AB  - A case of metachondromatosis is reported, the literature reviewed and the
      implications of the disease are discussed; one possible complication is avascular
      necrosis of the femoral capital epiphysis.

PMID- 8577505
TI  - Localized Langerhans cell histiocytosis of bone: treatment and follow- up in
      children.
AB  - We report a case of Langerhans cell histiocytosis (LCH) involving the right
      scapula in a 4-year-old child. Because of progressive shoulder pain and
      immobility methylprednisolone was injected directly into the lesion under
      computed tomography (CT) guidance. Follow-up studies with magnetic resonance
      imaging (MRI) and ultrasound (US) revealed continuous ossification of the
      osteolytic lesion with healing after 6 months. Plain films and CT confirmed the
      healing process. We consider intralesional corticoid instillation a safe method
      when performed under CT guidance. For initial evaluation and follow-up, MRI and
      US yielded reliable results in comparison to plain films and CT, thus helping to
      reduce the radiation dosage in children.

PMID- 8577507
TI  - Detection of cerebrovascular disease in patients with sickle cell disease using
      transcranial Doppler sonography: correlation with MRI, MRA and conventional
      angiography.
AB  - A prospective study of 58 patients with sickle cell disease (SCD) by transcranial
      Doppler sonography (TCD) included both MRI and MRA in patients over 7 years of
      age and those with abnormal TCD. Arteriography was performed in cases where a
      stenosis was suspected on TCD. Middle cerebral artery (MCA) and basilar artery
      (BA) velocities were significantly higher in the sickle cell hemoglobin SS group
      than in the hemoglobin SC group. Patients with a MCA mean velocity of over 1.90
      m/s had stenoses found by arteriography. Patients with unilaterally undetectable
      MCA flow had experienced a stroke and MCA thrombosis was confirmed at MRA and
      arteriography. We concluded that TCD is valuable in detecting arterial stenosis
      in SCD and will lead to consideration of these patients for intensive therapy,
      such as bone marrow transplantation (BMT) or transfusion regimes.

PMID- 8577508
TI  - Dedifferentiated chondrosarcoma in childhood: report of a case.
AB  - Dedifferentiated chondrosarcoma is an unconventional chondrosarcoma of
      distinctive pathology. The tumor, not previously reported in childhood, is
      characterized by a very poor prognosis with an average survival of only 6 months.
      Imaging features include a lytic lesion, focal calcifications, and a soft tissue
      mass.

PMID- 8577509
TI  - Radiological changes of frontometaphyseal dysplasia in the neonate.
AB  - The radiological manifestation of frontometaphyseal dysplasia has been well
      elucidated in later childhood and adulthood, but it has not been thoroughly
      clarified in the neonate. Here we report the radiological features of a neonate
      with frontometaphyseal dysplasia. Most features, including twisted ribs,
      increased interpediculate distances of the lumbar spine, flared ilia, mildly
      flared and bowed long bones, and arachnodactyly with undermodeled short tubular
      bones, were reminiscent of those found in older children and adults. A previously
      undescribed abnormality was advanced ossification of the femoral and tibial
      epiphyses.

PMID- 8577510
TI  - Aneurysmal bone cyst of the acromion: a case report.
AB  - The case of 6-year-old girl with an asymptomatic aneurysmal bone cyst of the
      acromion is reported. Such tumors are rarely located in the scapula and are
      especially rare in the acromion. The diagnosis was confirmed by biopsy and
      surgical resection of the lesion. Roentgenographic, CT and histologic features of
      the cyst are discussed.

PMID- 8577511
TI  - Abdominal sonography in the evaluation of heterotaxy in children.
AB  - Heterotaxy is a rare congenital disorder characterised by abnormal viscero
      vascular situs with either left or right isomerism that usually coincides with
      complex cardiac malformation. A precise diagnosis must be made for the selection
      of the most appropriate treatment. The diagnosis and evaluation of these
      conditions have been dependent on invasive studies such as angiocardiography,
      although more recently magnetic resonance imaging (MRI) has been advocated. In
      paediatric patients MRI is far from ideal because of the need for sedation and
      monitoring during the examination. The authors reviewed the modalities used in
      the evaluation of heterotaxy with emphasis on the use of ultrasonography,
      including pulse and colour flow Doppler imaging. A series of 14 children with
      heterotaxy is presented; ten with left abdominal isomerism (polysplenia) and four
      with right isomerism (asplenia). Results of abdominal sonography were compared
      with those of echo- and angiocardiography, surgery and autopsy. Of the ten
      children with left abdominal isomerism, two had no cardiac abnormalities. All
      those with right isomerism had a complex vitium. One patient with left abdominal
      isomerism proved to have right atrial isomerism. Some new reproducible patterns
      in viscero-vascular derangement are reported. The predictable patterns of left
      and right isomerism are outlined and atypical features discussed.

PMID- 8577512
TI  - Pseudomembranous colitis: CT findings in children.
AB  - A spectrum of nodular haustral thickening and an accordion pattern have been
      reported as specific features of pseudomembranous colitis (PMC) in adults. A
      retrospective review of nine patients with PMC was performed to assess whether
      this spectrum of CT findings also occurred in children. In four girls and five
      boys, CT scans were performed within 3 days of a positive stool toxin assay for
      Clostridium difficile. Documented CT abnormalities included nodular haustral
      thickening, the accordion pattern, colonic wall thickening, ascites, and
      pericolonic edema. These results were then correlated as to their impact on the
      clinical outcome. Circumferential colon wall thickening was identified in 7/9 (78
      %) patients (mean thickening 14.5 mm). Nodular haustral thickening was identified
      in 4/9 (44 %) and the accordion pattern in 2/9 (22 %). Other findings included
      pericolonic edema in 3/9 (33 %) and ascites in 1/9 (11 %). Wall thickening was
      confined to the left colon and rectum in 2/9 (22 %), to the right colon in 2/9
      (22 %), and involved the whole colon in 3/9 (33 %). Although CT findings
      associated with PMC in children may be suggestive for this diagnosis, CT is less
      specific than laboratory and clinical findings.

PMID- 8577513
TI  - Inflammatory bowel disease in glycogen storage disease type 1 B.
AB  - Chronic inflammatory bowel disease has recently been reported in association with
      glycogen storage disease type 1 B. We report two cases of children affected by
      this disease in whom chronic recurrent ileocolitis and severe oesophagitis
      developed.

PMID- 8577514
TI  - Gastric outlet obstruction: unusual ultrasonographic findings in the pyloric and
      antral regions.
AB  - The authors present the cases of four infants aged 2-4 months with symptoms
      suggesting gastric outlet obstruction. All four had US evaluation of the
      antropyloric region and upper GI series. Three of them underwent endoscopic
      investigations and three, surgery. US demonstrated hypertrophied pyloric muscle
      and, above all, antropyloric abnormalities in all cases, namely a solid mass
      within the pyloric canal, hypertrophy of the pyloric mucosa in two cases and a
      double juxtapyloric cyst with an ulcer. Differential diagnosis of the sonographic
      images is discussed in each case.

PMID- 8577515
TI  - Ileocolic intussusception presenting with bilious vomiting due to extrinsic
      duodenal obstruction.
AB  - We present a case of a child presenting with bilious vomiting due to extrinsic
      duodenal obstruction by an ileocolic intussusception. The clinical presentation,
      radiographic findings, and use of sonography are discussed.

PMID- 8577516
TI  - Pancreatic hydatid disease.
AB  - Pancreatic location of hydatid disease is exceptional. We report our findings in
      a 10-year-old asymptomatic patient who was admitted because of epigastric trauma.
      Radiological findings were considered secondary to trauma and therefore
      undervalued.

PMID- 8577517
TI  - Ultrasonographic diagnosis of intestinal ascariasis.
AB  - Ascaris lumbricoides is the most common roundworm in warm and temperate areas.
      Although radiological features of Ascaris lumbricoides are well defined, there
      are only a few reports on the ultrasonographic findings of intestinal ascariasis.
      In our two patients with no acute abdominal symptoms, intestinal ascariasis was
      initially diagnosed by abdominal ultrasonography. In both patients, tubular
      structures in the segments of the small intestine were demonstrated by
      ultrasonography.

PMID- 8577518
TI  - Operative gastric perforation: a rare complication of ventriculoperitoneal shunt.
AB  - Complications of ventriculoperitoneal shunts are reported in 24-47 % of cases.
      These include mechanical malfunction and infection, cerebrospinal fluid
      collection, shunt migration, and visceral perforation. Intestinal perforation,
      most commonly colonic, may be associated with meningitis or cerebral abscess.
      Gastric migration has been previously described as a late complication related to
      the use of stiff Raimondi coil-spring peritoneal catheters in children with
      malnutrition and abdominal adhesions. We report a case of operative gastric
      perforation, a rare complication which was detected prior to development of
      symptoms.

PMID- 8577519
TI  - Stenosis of the inferior vena cava caused by a traumatic diaphragmatic hernia:
      case report.
AB  - Post-traumatic obstruction of the inferior vena cava (IVC) or hepatic veins is
      uncommon. Ultrasound examination of a patient with hematuria revealed multiple
      intrahepatic venous collaterals. MRI showed a herniated right lobe of the liver
      and a narrowed hepatic segment of the IVC above the level of the patent right
      hepatic vein insertion. Multiple intrahepatic collaterals around the middle
      hepatic vein were demonstrated on inferior venacavography. The intrahepatic IVC
      was angulated and markedly narrowed below the right atrium. Surgical reduction of
      the herniated right lobe of the liver and repair of the ruptured diaphragm with
      Teflon felt was performed. On follow-up inferior venacavography, angulation of
      the IVC was relieved and the intrahepatic collaterals had disappeared. Hematuria
      subsided after operation.

PMID- 8577520
TI  - Transumbilical intravascular retrieval of an umbilical artery catheter.
AB  - We present a rare case of a broken umbilical artery catheter retrieved via a
      transumbilical approach with biopsy forceps.

PMID- 8577521
TI  - The radionuclide salivagram in children with pulmonary disease and a high risk of
      aspiration.
AB  - Purpose. We wanted to demonstrate the utility of the radionuclide salivagram in
      assessing children whose underlying medical problems suggest that aspiration of
      oral contents is a factor contributing to otherwise unexplained lung disease or
      recurrent pneumonias. Materials and methods. Following sublingual administration
      of 300 &mu;Ci (11.1 MBq) of technetium-99m sulfur colloid in a drop of saline,
      serial images were obtained for 60 min and evaluated for entrance of tracer into
      the major airways and lung parenchyma. Thirty-four studies were performed on 31
      patients (age: 3 weeks - 16.7 years, mean 5.5 years) with recurrent pneumonias or
      unexplained lung disease. All had medical conditions, most frequently
      neurological, predisposing to aspiration. Results. Pulmonary aspiration was
      detected in eight patients. All positive studies demonstrated aspirated tracer
      distal to the tracheal bifurcation, either in bronchi or in bronchi and lung
      parenchyma. Aspiration was bilateral in six cases. Clearance of aspirated tracer
      was noted in one patient. Conclusion. The salivagram is an effective tool for
      demonstrating aspiration of oral contents and the level to which aspirated fluid
      penetrates the tracheobronchial tree. Additionally, by allowing for the
      evaluation of clearance of aspirated tracer, the salivagram may provide
      information on the status of airway-protective mechanisms.

PMID- 8577522
TI  - Should intravenous contrast be used for chest CT in children with nonlymphomatous
      extrathoracic malignancies?
AB  - Intravenous contrast for thoracic CT examinations did not help in the staging of
      75 consecutive pediatric patients with extrathoracic malignancies. Thirteen
      developed pulmonary metastases. In three of four children with hilar or
      mediastinal metastatic adenopathy, the abnormal lymph nodes were seen on the
      plain chest radiographs as well as the CT.

PMID- 8577523
TI  - Tracheomalacia before and after aortosternopexy: dynamic and quantitative
      assessment by electron-beam computed tomography with clinical correlation.
AB  - To correlate the dynamics of tracheal collapse with clinical upper airway
      obstruction before and after aortosternopexy, seven boys and three girls (mean
      age, 10 months) underwent dynamic evaluation of the trachea by electron-beam
      computed tomography (EBCT). The site, extent, and severity of collapse were
      correlated with symptomatology and details of operative procedure. When > 50 %
      area collapse was used as the criterion for tracheomalacia, segmental involvement
      occurred above the aortic arch in all patients, extending to the aortic arch
      level in only four. Tracheomalacia involved two or fewer 8-mm levels in seven
      patients and more than two levels in three. Eight patients underwent one
      aortosternopexy procedure, resulting in clinical improvement in six and
      correlating well with EBCT findings. Of the remaining two patients who had single
      aortosternopexy and did not show clinical and radiographic improvement, one
      required operative repair of a vascular ring and the other continued to have
      recurrent respiratory tract infections. On the basis of EBCT findings, two
      patients required additional innominate arteriopexies: one improved, and the
      other remained symptomatic, requiring tracheostomy. EBCT is a noninvasive
      modality that allows preoperative diagnosis of tracheomalacia. More importantly,
      the operative decision and technique are guided by an objective and quantitative
      assessment of tracheal collapse.

PMID- 8577524
TI  - Congenitally short trachea and high carina with left mainstem bronchus
      compression by the ligamentum arteriosum.
AB  - We report a patient with congenitally short trachea (CST), defined as a decreased
      number of tracheal rings and high carina, who had respiratory distress and
      overaeration of the left lung secondary to extrinsic narrowing of the distal
      mainstem bronchus by ligamentum arteriosum compression.

PMID- 8577525
TI  - Tracheal anomalies, vascular compression and respiratory distress: the soft and
      hard and long and short of it.

PMID- 8577526
TI  - Pediatric air-gap chest digital imaging: an experimental study.
AB  - Geometrically magnified computed radiography (CR) chest radiographs can be
      obtained in children using the same techniques as for non-grid, non-magnified CR
      radiographs. The resulting magnification images have less scatter than grid
      images and better line pair resolution.

PMID- 8577527
TI  - Opercular malformations: clinical and MRI features in 11 children.
AB  - Opercular malformations are rare and complex brain malformations for which only
      very fragmented neuropathological descriptions have been reported. They are
      related to an abnormal development of both sylvian fissure and frontoparietal
      operculum. We report a retrospective clinical and MRI study of 11 patients
      presenting with opercular malformations. A congenital pseudobulbar syndrome was
      observed in six cases, various motor disorders in seven cases, mental retardation
      in six cases and epilepsy in four cases. The purpose of this study is to evaluate
      the main features of opercular malformations in children and to try to
      characterise this entity on the basis of its clinical features and MRI pattern.

PMID- 8577528
TI  - Crossed cerebellar atrophy in children: a neurologic sequela of extreme
      prematurity.
AB  - Unilateral atrophy of a cerebellar hemisphere occurring as a sequela of ischemic
      or destructive injury of the contralateral cerebral hemisphere is uncommon in
      children. We reviewed our experience with this phenomenon and found an unexpected
      association with extreme prematurity and a complicated perinatal course with a
      poor subsequent neurologic outcome. We retrospectively identified eight children,
      aged 8 months to 13 years, in whom cerebellar atrophy associated with cerebral
      injury was diagnosed on MR or CT, and reviewed their past medical history,
      neurologic findings, and neuroimaging studies. Seven patients were born extremely
      premature, EGA 25-28 weeks, and had severe perinatal intracranial hemorrhage.
      Neurologic problems include severe developmental delay in seven, spastic paresis
      in six, and seizures in five. Neuroimaging showed severe unilateral
      holohemispheric atrophy in four, bilateral asymmetric holohemispheric atrophy in
      two, and left temporoparietal atrophy in one. Cerebellar atrophy was unilateral
      in five and bilateral but asymmetric in two. Gliosis of the atrophic cerebellum
      occurred in one patient. Sequential neuroimaging in one patient showed evolution
      of crossed cerebellar atrophy at 8 months of age. The final patient, a term
      infant, had an idiopathic perinatal left cerebral infarct. In our experience,
      crossed cerebellar atrophy was an uncommon manifestation of extreme prematurity
      complicated by severe intracranial hemorrhage and/or ischemic necrosis of white
      matter. The cerebellar atrophy is most often a secondary degenerative phenomenon
      rather than a result of direct cerebellar injury.

PMID- 8577529
TI  - CT manifestations of pediatric intrathoracic desmoid tumors.
AB  - We describe the CT findings in two pediatric cases of intrathoracic desmoid tumor
      arising from the chest wall. In both cases, CT showed heterogeneously enhanced
      intrathoracic masses with destruction of the ribs.

PMID- 8577530
TI  - CT of staphylococcal anterior mediastinal abscess in an infant.
AB  - A 6-week-old girl presented with bronchiolitis secondary to respiratory syncytial
      virus. Eight days after admission she developed a Staphylococcus aureus infection
      at a previous intravenous cannula site. Despite antibiotic therapy this led to an
      anterior mediastinal staphylococcal abscess, which was drained surgically and the
      patient recovered. Mediastinal abscesses are rare in children: haematogenous
      spread of infection is an unusual aetiological factor and we believe this to be
      the first case reported due to an infected cannula site.

PMID- 8577531
TI  - Sclerosing hemangioma of the lung: radiological findings and pathological
      diagnosis.
AB  - We present a case of sclerosing hemangioma of the lung, revealed as a solitary
      round mass on routine chest radiography in a 14-year-old patient. CT and MRI
      findings were consistent with a solid neoplasm but no specific characteristics
      were identified. Analysis of the surgical biopsy material led to a cytological
      diagnosis of adenocarcinoma. Definitive diagnosis of sclerosing hemangioma of the
      lung was established on pathological examination of the whole surgical specimen.

PMID- 8577532
TI  - Maxillary sinus marrow hyperplasia in sickle cell anemia.
AB  - Marrow hyperplasia is a sequela of sickle cell anemia (SCA) and may be seen in
      the skull in children after 5 years of age [1]. The facial bones, except for the
      mandible and orbits, are usually not involved [1-3]. We report an unusual case of
      a 28-month-old black boy with SCA who presented with extensive marrow hyperplasia
      of the maxillary sinuses in addition to severe calvarial and mandibular changes.
      The imaging characteristics on CT (similar to other sites of marrow hyperplasia)
      and MR (low signal on both T1 and T2 sequences) should aid in making the correct
      diagnosis.

PMID- 8577533
TI  - Sinusitis and intracranial sepsis: the CT imaging and clinical presentation.
AB  - The CT imaging and clinical presentation in 14 children with coexistent
      intracranial sepsis and sinusitis were reviewed. A routine CT head scan (10-mm
      thick semi-axial slices through the cranium done before and after intravenous
      contrast medium administration) was found to be an inadequate initial
      investigation as the intracranial collection was missed in four patients and the
      abnormal sinuses not shown in six. In half the children the diagnosis of
      sinusitis was unsuspected at the time of admission. The dominant clinical
      features were fever, intense headache and facial swelling in early adolescent
      males. In this clinical setting we recommend: (1) the routine scan is extended
      through the frontal and ethmoidal sinuses and photographed at a window level and
      width showing both bone detail and air/soft tissue interfaces; (2) direct coronal
      projections are performed through the anterior cranial fossa if no collection is
      seen on the routine study; (3) an early repeat scan within 48 h if the initial
      study shows no intracranial pathology but the fronto-ethmoidal sinuses are
      abnormal and there is a high clinical suspicion of intracranial sepsis; and (4)
      in the presence of intracranial sepsis the vault is viewed at bone window
      settings to exclude cranial osteomyelitis.

PMID- 8577534
TI  - Vallecular cysts: report of two cases.
AB  - A vallecular cyst is an unusual cause of inspiratory stridor in the infant. We
      report our findings in two infants with this lesion. Thorough diagnostic
      evaluation is mandatory in the pediatric patient with concomitant inspiratory
      stridor and respiratory distress or feeding difficulties.

PMID- 8577535
TI  - Lymphatic air embolism: a new hypothesis regarding the pathogenesis of neonatal
      systemic air embolism.
AB  - Objective. Neonatal systemic air embolism (NSAE) has been thought to result from
      introduction of air into the pulmonary veins through hypothesized alveolar
      capillary fistula. The objective of this paper is to reassess the distribution of
      intravascular air visualized radiographically in this entity. Based on these
      data, an alternative theory for the pathogenesis of NSAE is proposed. Materials
      and methods. Four cases from our institutions and 21 additional reviewable
      published radiographs of NSAE were evaluated for the presence and location of
      intravascular air. Nonparametric statistical analysis was performed to determine
      if the predominance of intravascular air was venous or arterial in location, and
      to determine the presence or absence of pulmonary interstitial emphysema (PIE),
      pneumothorax, pneumomediastinum, and pneumopericardium. Results. Isolated
      systemic venous air was present significantly more often than isolated systemic
      arterial air (p < 0.0005). In addition, the presence of isolated right-sided
      cardiac air was found significantly more often than air within left heart
      chambers alone (p < 0.0005). PIE in patients with NSAE was found to be
      statistically more prevalent than pneumomediastinum or pneumopericardium, though
      similar in prevalence to pneumothorax. Conclusion. Our data support the
      hypothesis that intravascular air in NSAE is predominantly venous in location.
      PIE was found to be a very common associated finding in NSAE. Based on our
      current knowledge of pulmonary lymphatics, radiographic anatomy, and the
      lymphatic location of PIE, we propose that air within the pulmonary lymphatic
      system (PIE) gains access to the systemic venous system via lymphatic ducts,
      which results in the clinical entity NSAE. This readily explains the venous
      predominance of air in NSAE.

PMID- 8577536
TI  - Commentary: lymphatic air embolism: a proposed hypothesis.

PMID- 8577537
TI  - Tentorial hemorrhage associated with vacuum extraction in a newborn.
AB  - Neuroimages of tentorial hemorrhage associated with vacuum extraction have been
      rarely reported. The authors present the case of a 5-day-old newborn with this
      entity. CT showed retrocerebellar hemorrhage and MRI demonstrated tentorial
      hemorrhage extending inferiorly over the cerebellum and superiorly over the
      occipital regions. We believe that these imaging modalities are helpful in
      delineating the extent of the hemorrhage and assessing the prognosis.

PMID- 8577538
TI  - Primary Burkitt's lymphoma of the cranial vault in a child.
AB  - Non-Hodgkin s lymphoma in the cranial vault is rare, particularly in children.
      This report describes a 12-year-old boy who had a palpable and painless occipital
      skull mass and left hypoglossal nerve paralysis as the initial manifestations of
      Burkitt s lymphoma. Plain radiography, computed tomography and magnetic resonance
      imaging findings are presented.

PMID- 8577539
TI  - Tetrapolydactyly of postaxial type.
AB  - The case is presented of a 2-week-old boy with polydactyly occurring on the ulnar
      and fibular sides of the four extremities, which can be defined as
      tetrapolydactyly of postaxial type . Although the condition was not associated
      with syndactyly, it appears to represent a further example of a previously
      described anomaly, which was labelled tetrapolysyndactyly with postaxial type of
      polydactyly.

PMID- 8577540
TI  - Bilateral testicular large-cell calcifying sertoli cell tumor and recurrent
      cardiac myxoma in a patient with Carney's complex.
AB  - Large-cell calcifying Sertoli cell tumors are exceedingly rare testicular tumors
      which can be distinguished from pure Sertoli cell tumors by distinctive
      microscopic features and multifocal and bilateral calcifications [1]. We describe
      the characteristic sonographic appearance of the tumor with pathologic
      correlation. This tumor also constitutes one of the conditions of Carney's
      complex [2], which includes cardiac and skin myxomas, myxoid mammary
      fibroadenomas, spotty skin pigmentation, primary pigmented nodular adrenocortical
      disease, pituitary adenoma and unusual testicular tumors, especially large-cell
      calcifying Sertoli cell tumor. We report the case of a 10-year-old boy with four
      of the above conditions. Recognition of this complex is important as cardiac
      myxomas can lead to lethal complications. Because of a tendency for familial
      occurrence, family members should be screened carefully [3].

PMID- 8577541
TI  - Chilaiditi's syndrome in an infant: bowel loops mimicking mass lesions on
      sonography.
AB  - We report the case of a 6-month-old boy with Chilaiditi's syndrome presenting
      with tender hepatomegaly and abdominal pain. On sonography the interposed bowel
      loops mimicked a posterior hepatic or retroperitoneal mass. Although the majority
      of these cases may be radiological curiosities, patients can present with a
      variety of abdominal signs and symptoms. The correct diagnosis will be suggested
      on chest or erect abdominal films.

PMID- 8577542
TI  - Acute abdomen due to gastric volvulus: diagnostic value of a single plain
      radiograph.
AB  - A 2(1)/2-year-old child was admitted to hospital with acute abdominal pain and
      vomiting. A single large air-fluid level without additional bowel gas was seen on
      plain abdominal radiography. At laparotomy organoaxial volvulus of the stomach
      was found and partial gastric resection performed. A single bubble appearance may
      indicate gastric volvulus.

PMID- 8577543
TI  - Does hepatic subcapsular calcification in a premature baby reflect disease?
AB  - We followed a premature baby with hepatic subcapsular calcification of unknown
      etiology. Results of clinical and laboratory investigations and growth of the
      patient were normal. The causes of this condition are discussed and we suggest
      that it does not necessarily reflect disease.

PMID- 8577544
TI  - Clinical significance of resolution of chest X-ray findings in HIV-infected
      children with lymphocytic interstitial pneumonitis (LIP).
AB  - Lymphocytic interstitial pneumonitis (LIP) in HIV-infected children is generally
      associated with better prognosis as compared with children with Pneumocystis
      carinii pneumonia (PCP). We prospectively studied 12 cases of HIV-infected
      children with LIP over a 4-year period in an effort to document one aspect of the
      natural history of this clinical entity. Severe CD4 lymphocytopenia was
      associated with complete resolution of the chest X-ray findings in five patients,
      one of whom died of disseminated Mycobacterium avium complex. A second patient
      developed rapid-onset subacute HIV encephalopathy at the time when the CD4
      lymphocyte count declined from 589 to 39, and the lung findings resolved
      spontaneously. The resolution of the lung pathology may be the first indication
      of severe immune suppression and a warning of the increased risk for
      opportunistic infections. Therefore, in those settings where diagnostic
      laboratory facilities are not easily available, the resolution of the
      reticulonodular changes on chest radiographs is a poor prognostic sign in HIV
      infected children with LIP.

PMID- 8577545
TI  - Traumatic abdominal pseudoaneurysm secondary to child abuse.
AB  - Traumatic injury to the descending thoracic and abdominal aorta is uncommon in
      children and is usually secondary to recognized blunt trauma. Child abuse has not
      been previously reported as a cause. We report a 3-year-old boy who was kicked in
      the abdomen by his father. A resulting pseudoaneurysm was successfully resected.

PMID- 8577546
TI  - Pituitary apoplexy in adolescence: case report.

PMID- 8577547
TI  - Spine evaluation in children with anorectal malformations.
AB  - The value of radiography, ultrasound and magnetic resonance imaging (MRI) in
      detecting skeletal and intraspinal pathology was assessed in infants with
      anorectal malformations, and the need for spinal MRI examination in this group of
      patients was evaluated. Twenty-one infants were examined with radiography,
      ultrasound and MRI of the lower spine. The detection of skeletal and intraspinal
      abnormalities was compared for the three imaging modalities. Fifteen patients
      were normal in all three examinations. Radiography showed bony skeletal
      abnormalities in six children, although sometimes very subtle. By ultrasound both
      bony and cartilaginous malformations were detected in all six patients and by MRI
      in five patients. Five of the six children with skeletal abnormalities had
      intraspinal pathology, detected in all cases by ultrasound and MRI. However, the
      abnormalities were more clearly demonstrated by MRI than by ultrasound. Spinal
      radiographs must be examined carefully for abnormalities, because they can
      indicate the presence or absence of intraspinal pathology. Normal radiographic
      and sonographic appearance of spinal anatomy in children with anorectal
      malformation makes MRI superfluous, but if radiographs or ultrasound are
      abnormal, MRI should be used to accurately depict possible intraspinal pathology.

PMID- 8577548
TI  - Pre-operative MRI of anorectal anomalies in the newborn period.
AB  - Nine infants (six boys, three girls) with anorectal anomalies were examined in
      the immediate newborn period, prior to corrective surgery, with MRI. Three high,
      one intermediate and five low anomalies were found at MRI - one patient with a
      low lesion was subsequently found at surgery 2 months later to have a high
      anorectal anomaly. This infant had passed meconium per urethram soon after the
      MRI study, prompting the need for a protective colostomy and stressing the
      importance of a thorough clinical examination of babies with anorectal
      malformations. The MRI results and findings at surgery were in agreement in all
      other patients (n = 8). Hydronephrosis was evident in two and renal agenesis in
      one patient. Sacrococcygeal hypoplasia was found in two and two hemivertebrae in
      one infant. No spinal cord lesion was identified. One fistula was evident on MRI
      but four were later found at surgery. Uniformly hyperintense T 1 signal meconium
      was seen in all nine newborns, allowing for easy differentiation of rectal
      contents from rectal wall and the adjacent musculature. MRI can provide useful
      information regarding the development of the puborectal and external anal
      sphincter muscles, can help guide the pull-through procedure and help predict
      future continence pre-operatively in the newborn period.

PMID- 8577549
TI  - Effect of germinal matrix hemorrhage on terminal vein position and patency.
AB  - PURPOSE: Pathologic studies have suggested that periventricular intraparenchymal
      hemorrhages (IPH) occur as the result of compression and occlusion of terminal
      veins (TV) by germinal matrix hemorrhages (GMH). This study used color Doppler
      ultrasound techniques to test this hypothesis in vivo. MATERIALS AND METHODS:
      Twenty-four infants with 32 intracranial hemorrhages (20 GMH, 12 GMH/IPH) were
      evaluated during routine sonography with color and duplex Doppler ultrasound
      using an ACUSON 128 XP unit with 7-MHz linear and vector transducers. Maximum
      transverse dimension was obtained for each GMH. On coronal color Doppler
      ultrasound images, TVs were evaluated for displacement, presence of flow, and
      time average velocity (TAV). RESULTS: Abnormalities of the TV were common with
      ipsilateral GMH. Of 48 terminal veins evaluated, no flow was identified in 13 (27
      %), and flow in a displaced vein was seen in eight (17 %). TV abnormality
      occurred more frequently with GMH/IPH (90 %) than with GMH alone (52 %), and
      complete occlusion of the TV was more common in GMH/IPH (82 %) than in GMH alone
      (16 %, p < 0.002). GMH size correlated with increasing TV abnormality. Mean
      transverse GMH dimensions with unaffected TV, displaced TV, and occluded TV were
      8.2 +/- 1 mm, 10.3 +/- 1 mm, and 12.6 +/- 1 mm, respectively (p = 0.008). A small
      but significant trend was observed between maximum GMH dimension and decreasing
      TV velocities (r = - 0.5, p < 0.01). CONCLUSIONS: Obstruction of terminal veins
      by germinal matrix hemorrhage may play an important role in the pathogenesis of
      periventricular white matter hemorrhage.

PMID- 8577550
TI  - Lenticulostriate vasculopathy in twin-to-twin transfusion syndrome: sonographic
      and CT findings.
AB  - Lenticulostriate vasculopathy can be seen in an increasing number of clinical
      conditions, among which congenital infections and chromosomal abnormalities are
      best known. Two further patients with this ultrasound finding are reported, who
      were both recipients in the twin-to-twin transfusion syndrome.

PMID- 8577551
TI  - Increased renal medullary echogenicity in neonates.
AB  - The prevalence of increased renal medullary echogenicity in healthy neonates was
      looked for. A group of 178 neonates underwent renal ultrasound on the first and
      second days of life. On the first day of life 58% had hyperechoic material in
      their renal collecting system, whereas on the second day only 33% were found to
      have ultrasonographically demonstrable increased echogenicity in their kidneys.
      Urinary protein concentrations in infants with increased renal echogenicity were
      significantly higher than in those without increased renal echogenicity.

PMID- 8577552
TI  - Is there a single most appropriate imaging workup of a child with an acute
      febrile urinary tract infection?

PMID- 8577553
TI  - DMSA scanning: a pediatric urologist's point of view.

PMID- 8577554
TI  - Is there a role for renal scintigraphy in the routine initial evaluation of a
      child with a urinary infection?

PMID- 8577555
TI  - Unilateral occlusion of duplicated uterus with ipsilateral renal anomaly in young
      girls: a study with MRI.
AB  - Twenty-four young girls (mean age 13.0 years) with unilateral occlusion of a
      duplicated uterus and ipsilateral renal agenesis, dysplasia or hypoplasia were
      studied with magnetic resonance imaging (MRI) following ultrasound examination.
      Hydrocolpos (n = 4), hydrometrocolpos (n = 2), hematocolpos (n = 11),
      hematometrocolpos (n = 5), hematocolpometra, hematosalpinx (n = 3) and
      hematometra, hematosalpinx (n = 1) were noted (two of these patients had
      presented with hydrocolpos and hematocolpos before and after the menarche).
      Twenty-two of these girls presented with ipsilateral renal agenesis (right 11,
      left 11) with ectopic ureters to Gartner's duct cysts (GDC) in two, in one renal
      hypoplasia and in one renal dysplasia with ectopic ureters to GDC. MRI offered
      specific images of the genital tract, showing the exact type of mullerian duct
      anomaly and providing high diagnostic accuracy. Such preoperative identification
      of a uterine anomaly, complemented with appropriate surgical intervention, can
      assist young girls in achieving normal fertility in the future.

PMID- 8577556
TI  - The role of sonography in the detection of vaginal foreign bodies in young girls:
      the bladder indentation sign.
AB  - The cases of four young girls with vaginal foreign bodies, successfully diagnosed
      by ultrasound, are presented. The sonographic signs include varying echogenicity
      and acoustic shadowing, but always an indentation of the posterior bladder wall
      was clearly observed. Sonography should be considered as the first step in the
      evaluation of suspected vaginal foreign bodies in young girls.

PMID- 8577557
TI  - Acute focal bacterial nephritis in childhood brucellosis.
AB  - Brucellosis is an infectious disease transmitted from various animal hosts to
      man. In children the most common route of infection is unpasteurized milk or milk
      products. Brucellosis affects the urinary tract uncommonly, most frequently
      causing orchioepididymitis. We report the case of a 4-year-old boy with
      brucellosis who developed acute focal bacterial nephritis (AFBN), documented by
      sonography, gallium scan, and computed tomography. After appropriate treatment
      his symptoms and his sonographic abnormality resolved completely. To the best of
      our knowledge, this is the first report of the association of AFBN and
      brucellosis.

PMID- 8577558
TI  - Escherichia coli O157:H7-associated hemolytic-uremic syndrome: value of colonic
      color Doppler sonography.
AB  - Hemolytic-uremic syndrome associated with Escherichia coli O157:H7 presents with
      a gastrointestinal prodrome. During this prodrome the disease may be difficult to
      differentiate from acute colitis and other hemorrhagic gastrointestinal diseases.
      We have found that color Doppler sonography in patients with E. coli-associated
      hemolytic-uremic syndrome of the colon demonstrates a strikingly avascular, thick
      walled colon. In the correct clinical setting, this finding should allow a
      diagnosis during the prodromal phase.

PMID- 8577559
TI  - Intrapelvic Wilms' tumor simulating xanthogranulomatous pyelonephritis.
AB  - A 2-year-old boy presented with an atypical renal mass with extension into the
      pyelocalyceal system and distal ureter which was diagnosed initially as
      xanthogranulomatous pyelonephritis (XGP). The final diagnosis was intrapelvic
      Wilms tumor extending into the ureter. In the literature, only three patients
      have been described with Wilms tumor extending into the ureter, none of whom had
      a continuous extension into the distal ureter.

PMID- 8577560
TI  - Perlman syndrome: report of a case with additional radiographic findings.
AB  - Perlman syndrome is a rare autosomal recessive syndrome of macrosomia and
      nephromegaly associated with a significant predisposition to Wilms tumor. We
      report a premature infant with Perlman syndrome to demonstrate additional
      manifestations of this condition: large cisterna magna, intestinal malrotation,
      and skeletal abnormalities.

PMID- 8577561
TI  - Congenital mesoblastic nephroma metastatic to the brain: a report of two cases.
AB  - Congenital mesoblastic nephroma was originally believed to be a universally
      benign neoplasm. More recently, aggressive congenital mesoblastic nephromas have
      been described with local recurrence and/or metastases. We report two patients
      with documented congenital mesoblastic nephroma which later metastasized to the
      brain.

PMID- 8577562
TI  - Wilms tumor: unusual manifestations.
AB  - Wilms tumor is an important renal malignancy with which pediatric radiologists
      must be familiar. Although the imaging features are usually typical for renal
      masses, unusual imaging features of Wilms tumor may confound the imaging
      physician. This review highlights the less common imaging appearances of Wilms
      tumor which pediatric radiologists may encounter.

PMID- 8577563
TI  - Renal lymphoma mimicking clear cell sarcoma in a pediatric patient.
AB  - Lymphoma involving the kidneys typically presents as bilateral renal enlargement
      with multiple nodules [1-6]. Solitary masses, diffuse parenchymal infiltration,
      or engulfment of the entire kidney by diffuse disease may occur but are more
      rare. We report the case of a child with non-Hodgkin s lymphoma presenting as a
      focal unilateral renal mass with bony metastases.

PMID- 8577565
TI  - Raccoon eyes and the MIBG super scan: scintigraphic signs of neuroblastoma in a
      case of suspected child abuse.
AB  - The authors report on an infant suspected of having been abused, who presented
      with periorbital edema and ecchymoses (clinical "raccoon eyes"). The pattern of
      the nuclear medicine bone scan suggested neuroblastoma rather than trauma. Both
      the bone scan and the subsequent MIBG scan revealed multiple abnormalities,
      including markedly increased activity around the orbits, that we termed the
      scintigraphic raccoon eyes sign. In addition, the grossly abnormal MIBG scan
      demonstrated avid uptake of MIBG throughout the entire skeleton with essentially
      complete absence of visualization of the liver and heart (the MIBG super scan ).
      These signs have not previously been described in an infant or a child with
      neuroblastoma.

PMID- 8577564
TI  - MRI of papillary meningiomas in children.
AB  - We report two cases of papillary meningioma in children. The MRI appearance of
      this special type of meningioma is described for the first time. Both lesions
      were dura based and associated with cystic components. We review the literature
      pertaining to this type of meningioma and discuss the differential diagnosis of
      the MRI appearance. Because this is a malignant type of meningioma, early
      diagnosis and surgical intervention are important in the management of patients.

PMID- 8577566
TI  - Neuroblastoma presenting clinically as hip osteomyelitis: a "signature" diagnosis
      on skeletal scintigraphy.
AB  - At their initial emergency room presentation, four children were thought to have
      hip osteomyelitis. Skeletal scintigraphy, however, demonstrated multiple areas of
      abnormal tracer uptake in the bones in all four, and in three there was abnormal
      uptake in a soft tissue abdominal mass. The skeletal scintigraphic findings
      promptly led to the correct diagnosis of neuroblastoma.

PMID- 8577567
TI  - Cystic metastatic cerebral neuroblastoma.
AB  - Intracerebral neuroblastoma is an exceedingly rare manifestation of intracranial
      neuroblastoma and has been described as a solid lesion. Cystic metastatic
      intracerebral neuroblastoma has not been described. We report a case of
      histologically proven metastatic intracerebral neuroblastoma presenting in a
      cystic form 1 year after diagnosis and treatment of a solid intra-abdominal
      neuroblastoma. The imaging and clinical appearance of this case was
      indistinguishable from that of intracerebral cystic lesions caused by infection
      or inflammation. It has been suggested that, due to more aggressive treatment of
      neuroblastoma, patients are surviving longer and consequently intracranial
      involvement is becoming more frequent. It is important to be aware of this cystic
      manifestation of the disease.

PMID- 8577568
TI  - Paraneoplastic encephalomyelitis in a child with neuroblastoma.
AB  - We present the case of a 12-year-old boy who developed progressive limbic
      dysfunction associated with a posterior cord syndrome in conjunction with complex
      partial seizures and intrathecal synthesis of IgG. Although the cerebral CT scan
      appeared normal, MR imaging showed signal abnormalities in both temporal lobes.
      As these clinical features reminded us of the well-known paraneoplastic
      encephalomyelitis (PNEM) in adults, we looked for a tumour and found a pelvic
      neuroblastoma. The diagnosis of PNEM was supported by the discovery of the
      antibody anti-HU in the serum of our patient.

PMID- 8577569
TI  - The cranes and skyhooks of Daniel C Dennett.

PMID- 8577570
TI  - Modulation of the rod-and-frame illusion by additional external stimuli.
AB  - The presence of an additional external upright frame was studied in three
      experiments to separate the role of visuovestibular, global, and local mechanisms
      in the rod-and-frame illusion (RFI). In the first experiment, carried out in a
      dark room, the external frame surrounded a large tilted frame. Rod-setting errors
      to the vertical were abolished with the additional-frame condition (at 22 degrees
      inner-frame tilt) confirming earlier findings. However, small, residual direct
      (at 11 degrees inner-frame tilt) and indirect effects (at 33 degrees inner-frame
      tilt) were still present, indicating the persistence of global visual processing.
      In the second experiment, the RFI in the dark was compared with the RFI with the
      lights on. Turning the light on abolished the effect at 22 degrees and 33 degrees
      frame tilt; however, a small direct effect was maintained at 11 degrees frame
      tilt. These two studies indicate that the addition of veridical vertical
      information abolishes the effect owing to visuovestibular mechanisms. In the
      third experiment, a small rod and frame was used with the lights on (a condition
      abolishing visual-vestibular interaction). In the case of a small gap between the
      rod and the inducing frame (a condition which maximises local processing), the
      effect of the outer upright frame was negligible; this indicates that the
      additional frame had no effect on local processing. In the case of a large gap (a
      condition which minimises local processing), the external square reduced the
      illusion, indicating its modulating effect on visual global processing. Overall,
      an upright external frame exerts a differential influence depending on which
      mechanisms contribute most to the RFI in a given experimental condition.

PMID- 8577571
TI  - Visual factors affecting the rod-and-frame illusion: role of gap size and frame
      components.
AB  - In two studies the effect of the distance between the tip of the rod and the
      frame sides (gap) in the rod-and-frame (RF) illusion was examined and the effect
      of a full-square condition was compared with that of two different frame
      amputations. In both studies, there were more rod-setting errors in the direction
      of the tilt of the inducing figure with a small gap than with a large one. These
      findings are consistent with the idea that in the case of small gap size local
      interactions contribute to determining the RF illusion. The actual length of the
      rod was varied in order to keep the gap constant across different frame tilts;
      therefore these findings cannot be due to the co-variation between gap size and
      frame tilt which is typical of standard apparatuses. The effect of frame
      amputations was compared to the full-square condition. According to Wenderoth and
      Beh, amputations that maintain the two orthogonal contours of the square produce
      the typical angular function of the RF illusion. This prediction was confirmed in
      both studies. However, results indicate that the full square has a stronger
      illusory effect in the case of a small degree of tilt of the inducing stimulus,
      irrespective of gap size. It is suggested that this 'square superiority' effect
      is related to global, not local, mechanisms. To pursue Wenderoth and Beh's
      observations, amputations close to the vertical meridian were used in one
      experiment and those close to the horizontal meridian in the second experiment.
      Contrary to predictions, these conditions produced overlapping results.

PMID- 8577572
TI  - Orientation discrimination for bars defined by orientation texture.
AB  - A texture pattern consisting of short (0.2 deg) lines contained a 5.0 deg x 1.4
      deg texture-defined bar. The bar was rendered visible by the difference in
      orientation (2 theta) between the lines inside the bar and outside the bar.
      Orientation-discrimination threshold for the texture-defined bar was a U-shaped
      function of 2 theta over the range 2 theta = 0 degree to 2 theta = 180 degrees.
      The lowest threshold was at 2 theta = 90 degrees, and was 0.57 degrees for both
      subjects tested. This threshold was little different from the lowest values of
      threshold for motion-defined bars, disparity-defined bars, and colour-defined
      gratings reported elsewhere. A luminance-defined bar was created by switching off
      all texture lines outside the texture-defined bar. Orientation-discrimination
      threshold fell to a limiting value as the luminance contrast of this bar was
      progressively increased. The lowest value of orientation discrimination for the
      luminance-defined bar (0.42 degrees and 0.35 degrees for the two subjects) was
      not greatly less than the lowest value for the texture-defined bar.

PMID- 8577573
TI  - Viewing angle and the perceived orientation of pictorial elements: geometric or
      representational effects?
AB  - The role of geometric shape properties in determining the perceived orientation
      (heading) change of picture elements was investigated in four experiments. In
      experiment 1 the systematic change in perceived heading of each of a depicted
      team of horses which projected irregular geometric shapes was measured. In
      experiment 2, involving silhouettes, the perceptual axes of these same horse
      shapes, together with those of a pair of enantiomorphic deltoid shapes, were
      derived. These derived shape axes were used in experiment 3, along with single
      oblique contours, to determine the degree of heading shift as a function of the
      complexity and orientation of the shape. The degree of heading shift was
      remarkably similar for both silhouette shapes and the single contours when the
      axes were oblique but, whereas vertical orientation was predicted to abolish
      heading shift, this was only true for the deltoid shapes. In experiment 4 a
      possible explanation of the nonpredicted heading shift for the vertically
      oriented horse silhouettes was investigated. Subjects' individual estimates of
      the axes of the horse shapes, rather than a group mean value, were used to set
      the horse shapes to the vertical. When viewing was from two positions no
      significant heading change with view was found. Taken as a whole the data suggest
      that the geometric properties of patterns, rather than their representative
      nature, determine the very obvious heading shift when pictures are viewed from
      different angles.

PMID- 8577574
TI  - Size constancy in structure from motion.
AB  - The relative motions of points in a structure-from-motion display involving
      parallel projection provide depth information in an object-centered framework:
      differences in velocity do not reflect differences in distance from an eyepoint.
      In contrast, size constancy is generally regarded to be a perspective effect,
      based on the relationship between projected size and distance from an eyepoint.
      Five subjects judged the relative sizes of objects in structure-from-motion
      scenes. Although the scenes were displayed without perspective, judged size was
      related to the simulated separation in depth of the objects. These results
      suggest that relative depths recovered from object-centered information are
      incorporated into a viewer-centered framework.

PMID- 8577575
TI  - A new motion illusion related to the aperture problem.
AB  - A previously unreported motion illusion is described. Oblique lines that drift
      smoothly on the retina in a vertical direction appear to be displaced laterally.
      The effect occurs both for moving lines under fixation and for stationary lines
      under ocular tracking of an external target. Orientation, length, and homogeneity
      of the obliques affect the magnitude of illusory displacement. We propose that
      this illusion is associated with a misregistration of the direction of
      displacement occurring, in lines slanted relative to the axis of their motion,
      because of the aperture problem.

PMID- 8577576
TI  - Duration illusions in a train of visual stimuli.
AB  - The first stimulus in a sequential train of identical flashes of light appears to
      last longer than those in the middle of the train. Four flashes (each 600 or 667
      ms) were presented and the first was shortened until it appeared to have the same
      duration as that of the next. The duration of the first stimulus was found to be
      overestimated by about 50%. The illusion was unaffected by stimulus contrast,
      size, or interflash interval (between 100 and 600 ms). For some subjects, the
      last stimulus in the train also appeared to be about 50% longer than the
      penultimate flash. The results are discussed in terms of theories of how
      attention, arousal, and stimulus processing can affect duration perception. The
      mechanisms activated are peculiar to the visual system, since no similar illusion
      of duration was consistently experienced with a train of auditory tones.

PMID- 8577577
TI  - Young children's judgments of relative mass of two objects in a head-on-collision
      event.
AB  - The purpose in this study was to investigate the ability of young children to
      judge the relative mass of two objects depicted on a CRT monitor as colliding
      head-on with each other, and to determine which feature of a collision event they
      depend on for their judgments. In the first experiment it was shown that half of
      the 4-year-olds and most of the 5-year-olds and 6-year-olds consistently judged
      the slower object to be heavier when the velocities of the two objects before
      collision were the same and those after collision were different. In the second
      experiment young children's judgements of relative mass in noncollision events in
      which two objects only moved in opposite directions at different speeds were
      examined. Results showed that half of the 5-year-olds and most of the 6-year-olds
      tended to assume consistently that the slower object was heavier. However, the 4
      year-olds did not show any clear tendency. The third experiment was planned to
      examine young children's judgments of relative mass in different collision events
      in which only the precollision velocities of two colliding objects were
      different: half of the 6-year-old children judged the slower object to be
      heavier, but the rest of them and half of the 5-year-old children consistently
      gave the opposite responses. These were based upon the delay between the starts
      of motion of the two objects. The 4-year-olds did not show any tendency, as in
      experiment 2. The results indicate that young children can specify the kinetic
      information about relative mass from the kinematics of collision events when
      viewing an appropriate collision event, and that both the precollision phase and
      the postcollision phase contribute to the judgement of relative mass.

PMID- 8577578
TI  - Perceptual abnormalities in Parkinson's disease: top-down or bottom-up processes?
AB  - A wide variety of perceptual impairments have been reported in patients with
      Parkinson's disease (PD) in recent years; the underlying causes of these
      impairments have been variously attributed to different levels of the visual
      cognitive system, from the retina to frontal cortex. Parkinsonian perceptual
      abnormalities could thus be interpreted as indirectly caused either by 'bottom
      up' effects, stemming from dopaminergic dysfunction in the retina, or by 'top
      down' effects, stemming from deficits in attention due to disturbances in the
      striatal-frontal system. Alternatively, a direct visuospatial impairment, perhaps
      related to the motor symptoms, has been considered. Data on three basic aspects
      of visual perception (3-D stereo vision, figure-ground discrimination, and
      pattern perception) which might be expected to give difficulty to PD subjects
      suffering changes in early processing mechanisms are reported. Visual complexity
      and the degree of mental manipulation of the material required both varied in
      different parts of the tests. PD patients were on stable drug regimens. It was
      found that disease severity interacted with performance: patients with mild PD
      showed little perceptual abnormality, patients with moderate PD showed only top
      down effects, and patients with severe PD showed evidence both of top-down and of
      bottom-up deficits. Thus it appears that any retinal effects on perception in PD
      occur only in the advanced stages of the disease; in earlier stages any visual
      dysfunction probably reflects top-down disturbances from higher levels of the
      cognitive-behavioural system.

PMID- 8577579
TI  - Battle of the breast in the classroom.

PMID- 8577580
TI  - Sanctioned to starve.

PMID- 8577581
TI  - Controlled aggression.

PMID- 8577582
TI  - On duty. Interview by Michael Walker and Chris Hart.

PMID- 8577583
TI  - Responding to the results of the Beverly Allitt inquiry.
AB  - In May 1993, while many nurses were gathered in Harrogate for the RCN's annual
      congress, the verdicts of the trial of enrolled nurse Beverly Allitt were
      announced. The nursing world found it difficult to believe that while employed on
      a six-month fixed-term contract on the children's ward at Grantham and Kesteven
      District General Hospital Ms Allitt had been convicted of murdering four children
      and injuring nine others. The following February the report of the Allitt inquiry
      was published. The inquiry team, chaired by Sir Cecil Clothier, had met 35 times,
      interviewed 94 witnesses in person, received written submissions from a number of
      interested bodies and reviewed numerous other relevant documents. This paper
      reviews the inquiry's original recommendations and outlines the actions that have
      been taken to implement them.

PMID- 8577584
TI  - Working with mental distress.
AB  - Although there is a need to learn from the experience of the Allitt inquiry the
      notion of 'health checks' for staff is fraught with complications. Not only might
      it be impossible to isolate nurses who are 'unhealthy', but the measures might
      discourage nurses from admitting to psychological problems. Most important, the
      therapeutic relationship between nurses and those in their care might be
      threatened.

PMID- 8577585
TI  - Incorporating the framework of Vision for the Future.
AB  - In April 1995 King's Healthcare NHS Trust became a national development site for
      implementing the 12 targets for quality care delivery set out in Vision for the
      Future. This paper describes the local strategy of the trust and its progress in
      meeting the targets.

PMID- 8577586
TI  - Dorrell's colour-blind cuts.

PMID- 8577587
TI  - The adrenal gland. 3.

PMID- 8577588
TI  - A place to be heard.

PMID- 8577589
TI  - Falling trend.

PMID- 8577590
TI  - Muscle woman.

PMID- 8577591
TI  - Solving conflict in the ward.

PMID- 8577592
TI  - Age concern.

PMID- 8577593
TI  - Professional development. Parkinson's disease. The role of the nurse.

PMID- 8577594
TI  - Built-in resistance.

PMID- 8577595
TI  - Colonised community.

PMID- 8577596
TI  - Trust demands HIV test for pool births.

PMID- 8577597
TI  - On-line midwives.

PMID- 8577598
TI  - The bit of a shrinking NHS.

PMID- 8577599
TI  - The 'I's don't have it.

PMID- 8577600
TI  - Letter from Poland.

PMID- 8577601
TI  - Care of the older hypothermic patient using a self-care model.
AB  - This paper focuses on the problem of hypothermia and provides an overview of its
      causes, signs and symptoms. A case study of a patient who was admitted to an
      acute assessment of the elderly ward with hypothermia is described and the use of
      Orem's self-care model of nursing is explained.

PMID- 8577602
TI  - Accidental hypothermia: a guide to treatment in the field.
AB  - This paper is a review of the guidelines laid down by Dr D. Snadden, a former
      medical officer of the Cairngorm mountain rescue team, for first-line treatment
      of the hypothermic casualty.

PMID- 8577603
TI  - How postnatal support groups can benefit new parents.
AB  - This paper highlights the need for support for new mothers and explains how
      health visitors researched the need for, and set up, a postnatal support group.

PMID- 8577604
TI  - Laboratory diagnosis of acute myocardial infarction.
AB  - This paper explains how laboratory testing of blood can provide additional
      evidence to clinical examination and electrocardiogram either to support or
      exclude a diagnosis of myocardial infarction. Current practice is described and
      new developments outlined.

PMID- 8577605
TI  - Why do nurses not make use of a solid research base?
AB  - Although research-based practice was advocated in 1972 in the Briggs report, it
      is suggested that nursing has failed to rise to the challenge. This paper
      examines some of the explanations why nurses have difficulty in combining
      research-based theory and practice.

PMID- 8577606
TI  - Launchpad to health.

PMID- 8577607
TI  - Focus on need.

PMID- 8577608
TI  - Raising the spirits.

PMID- 8577609
TI  - Starched collars & starch baths.

PMID- 8577610
TI  - Sweet talk.

PMID- 8577612
TI  - Bullous skin disorders.

PMID- 8577611
TI  - Involving the patient in care.

PMID- 8577613
TI  - Teamwork in burn care.

PMID- 8577614
TI  - Professional development. Parkinson's disease. Revision notes.

PMID- 8577615
TI  - Make ripples.

PMID- 8577616
TI  - Administering Navelbine: a controversy.

PMID- 8577617
TI  - Patient-induced dehydration--can it ever be therapeutic?

PMID- 8577618
TI  - Impact of silicone implants on the lives of women with breast cancer.
AB  - PURPOSE/OBJECTIVES: To describe the impact of silicone implants on the lives of
      women with breast cancer. DESIGN: Qualitative analysis of telephone interview
      data. SAMPLE: 120 women from across the United States who have reported to the
      Food and Drug Administration problems with breast implants following
      mastectomies. METHODS: Telephone interviews were used to gather responses to 110
      questions. Qualitative analysis of narrative data was linked with quantitative
      data. MAIN RESEARCH VARIABLES: Concerns and feelings about breast implants;
      potential problems with silicone implants; source of information about problems;
      how they coped with the silicone implant controversy; problems related to their
      breast implants; the effect of health problems on day-to-day activities,
      relationships with significant others, work, and any other important aspects of
      their lives; and advice they would give other women regarding breast implant
      surgery. By linking the qualitative analysis of narrative data with quantitative
      data, the investigators sought to answer the following research question: Do the
      patterns of responses differ based on specific systemic physical problems,
      reported localized breast problems, or implant problems? FINDINGS: The women
      reported poorer quality of life and feelings of worry and anger because of health
      problems. They perceived they had received incomplete information and often had
      complaints dismissed by their healthcare providers. Most of them would not
      recommend silicone implants for patients undergoing mastectomy. The women's
      levels of satisfaction were directly associated with their feelings of being
      informed and the type of health problems they experienced. CONCLUSIONS: Women
      need reconstruction options following mastectomy, however, use of silicone
      implants can result in additional health problems and decreased quality of life
      as a result of those problems. IMPLICATIONS FOR NURSING PRACTICE: Nurses can
      assume the role of breast health educator, which includes counseling women with
      breast cancer about breast implants and other reconstructive options. Study
      results will help health providers care both for those patients considering
      treatment options and those coping with the problems and concerns related to
      their breast implants. Women should be told the inherent risks and complications
      associated with breast implants and also told when "we don't know."

PMID- 8577619
TI  - Lymphedema: incidence, pathophysiology, management, and nursing care.
AB  - PURPOSE/OBJECTIVES: To review the incidence, pathophysiology, and management of
      lymphedema and discuss relevant nursing implications. DATA SOURCES: Published
      articles, book chapters, and clinical experience. DATA SYNTHESIS: Lymphedema may
      result from cancer and cancer treatment. Any surgical intervention and radiation
      therapy can result in interruption and obstruction of the lymph channels. Signs
      and symptoms of lymphedema include edema, pain, numbness, and limited range of
      motion. CONCLUSIONS: Physical and psychological distress may result from
      lymphedema. IMPLICATIONS FOR NURSING PRACTICE: Nursing care should focus on
      patient education that emphasizes risk factors for the development of lymphedema,
      prevention measures, and self-care activities. Nursing research is needed to
      determine specific informational needs of the patient, appropriate teaching
      techniques, and optimal times for delivery of information.

PMID- 8577620
TI  - A professional code of ethics: providing a moral compass for turbulent times.
AB  - PURPOSES/OBJECTIVES: To describe the importance of a professional code of ethics
      and values in guiding and supporting the practice of nurses and to present the
      proposed Oncology Nursing Society (ONS) Statement of Core Values. DATA SOURCES:
      Published articles and books on nursing ethics and bioethics, as well as authors'
      clinical experiences. DATA SYNTHESIS: Ethical quandaries are commonplace for
      nurses, and the contemporary context of health care has created new concerns and
      redefined others. Throughout its history, nursing has been an ethical endeavor,
      with nurses attempting to sift through complex ethical issues and fulfill their
      professional responsibilities. A professional code of ethics and values
      explicates the goals and norms of the profession and provides direction for
      practice. CONCLUSION: Together, the profession's code of ethics and the proposed
      ONS Statement of Core Values serve as a resource to guide oncology nurses as they
      develop an ethically competent practice and confront contemporary ethical
      challenges. IMPLICATIONS FOR NURSING PRACTICE: The goal of developing an
      ethically competent practice, maintaining professional integrity, and rendering
      quality patient care is of vital concern to oncology nurses. Familiarity with and
      commitment to the primary ethical precepts and values of the profession are
      essential to accomplishing this goal.

PMID- 8577621
TI  - Quality of life of long-term adult survivors of autologous bone marrow
      transplantation.
AB  - PURPOSE/OBJECTIVES: To extend the knowledge of quality of life (QOL) of survivors
      of allogeneic bone marrow transplantation (BMT) to include survivors of
      autologous BMT. To determine the appropriateness of using a reliable, valid,
      allogeneic BMT QOL instrument for survivors of autologous BMT. DESIGN: Cross
      sectional, descriptive, replication survey. SETTING: An autologous BMT program in
      a National Cancer Institute-designated comprehensive cancer center. SAMPLE: All
      survivors of autologous BMT (N = 37) at the center were recruited; 29 survivors
      participated (85% response rate). METHODS: Three mailed questionnaires: the City
      of Hope quantitative QOL-BMT instrument and qualitative questionnaire and an
      investigator-developed demographic questionnaire. MAIN RESEARCH VARIABLES: QOL,
      autologous BMT treatment, disease type, age, gender, employment, and date of
      transplant. FINDINGS: Global QOL was high (mean = 8.17 on a 1-10 scale). Most
      respondents experienced few long-term physical disruptions and had only mild
      psychological distress. Fatigue, sexuality concerns, and family distress created
      by the illness were the most negatively rated items. Content, face, and construct
      validity of the QOL-BMT instrument in the autologous BMT population were
      acceptable. Overall internal consistency reliability of the tool, as measured by
      Cronbach's alpha, was 0.82. Themes of uncertainty, concern about relapse, and
      pain were reported in the qualitative data but not revealed by responses to the
      QOL-BMT instrument. CONCLUSIONS: The majority of survivors of autologous BMT
      reported few physiologic disruptions and above-average QOL. The City of Hope QOL
      BMT instrument had acceptable reliability and validity when adapted for survivors
      of autologous BMT. Addition of items related to uncertainty, pain, and concern
      about relapse could further strengthen its validity. IMPLICATIONS FOR NURSING
      PRACTICE: Most survivors of autologous BMT can expect above-average QOL.
      Incorporating results of QOL evaluation in the informed consent process may help
      BMT candidates in making the decision to undergo the procedure by providing a
      more complete picture of life after BMT. However, since a minority of patients
      will experience continued disruptions in any one of the QOL domains, healthcare
      providers need to conduct comprehensive follow-up evaluations to determine which
      patients may need referral to the specialized services of a survivor clinic.

PMID- 8577622
TI  - A survey of lung cancer patient-education materials.
AB  - PURPOSE/OBJECTIVES: To examine the readability and content of educational
      materials developed specifically for patients with lung cancer. DATA SOURCES:
      Lung cancer patient-education materials identified in a survey of 54 cancer
      organizations and institutions and a literature review. DATA SYNTHESIS: Only five
      educational resources specifically developed to address the needs of patients
      with lung cancer were identified. Only two addressed dyspnea, fatigue, loss of
      appetite, pain, risk of recurrence, sexuality, smoking cessation, rehabilitation,
      or palliation. None addressed reduced functional abilities resulting from disease
      or treatment. All of the materials reviewed were written at a reading level of
      10th grade or higher. CONCLUSIONS: Current lung cancer patient-education
      materials are inadequate and require advanced reading skills. IMPLICATIONS FOR
      NURSING PRACTICE: Distressing disease- and treatment-related symptoms, as well as
      psychological and social stressors, complicate coping with lung cancer. Existing
      educational resources for patients with lung cancer require modification and need
      to be written at more appropriate reading levels. Further research must assess
      and clarify the information needs of patients and determine the best method of
      delivering the information to patients.

PMID- 8577623
TI  - Barriers to breast and cervical cancer screening in underserved women of the
      District of Columbia.
AB  - PURPOSE/OBJECTIVES: To identify barriers to breast and cervical cancer screening
      services from the perspective of medically underserved women of the District of
      Columbia (DC) that may influence intentions to perform breast and cervical cancer
      screening behaviors; to determine any relationship between attitudes and
      influence of significant others on intended behaviors; and to identify a
      relationship between the site where services are provided and the underserved
      women's intentions to engage in screening behaviors. DESIGN: Cross-sectional,
      correlational. SETTING: Breast and cervical cancer screening clinics in DC.
      SAMPLE: 339 medically underserved, adult women. METHODS: Face-to-face
      investigator-conducted interviews. MAIN RESEARCH VARIABLES: Demographic and
      contextual variables as well as attitudes and influence of significant others.
      Intention to have a mammogram or Pap test or perform breast self-examination
      (BSE) monthly. FINDINGS: Intention to have a mammogram was positively related to
      influence of significant others and negatively related to uncaring healthcare
      professionals. Intention to have a Pap test had a positive relationship with
      one's attitude toward the test and with the influence of significant others.
      Intention to perform BSE was positively related to attitude toward and previous
      performance of BSE and influence of significant others. No significant
      relationships were observed between intention to perform screening behaviors and
      demographic variables. CONCLUSIONS: Factors that influence women's attitudes
      toward screening and intention to perform these behaviors include previous
      screening behaviors, influence of significant others, and relationships with
      healthcare professionals. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses are
      well-positioned to develop and test intervention strategies designed to increase
      access to and compliance with recommended screening guidelines among the
      medically underserved. Findings from this study potentially could guide
      development and evaluation of such strategies that are sensitive to this special
      population.

PMID- 8577624
TI  - Skin cancer prevention by parents of young children: health information sources,
      skin cancer knowledge, and sun-protection practices.
AB  - PURPOSE/OBJECTIVES: To describe and evaluate parents' skin cancer prevention
      knowledge, sun-protection practices for themselves and their children, and use of
      health information sources. DESIGN: Cross-sectional survey. SETTING: A medium
      sized (population 700,000) metropolitan area in the southwestern United States.
      SAMPLE: 205 adults, ages 19-56, with children under age 13. Fifty-three percent
      of the subjects were female, 72% were Caucasian, 22% were Hispanic, 69% were
      educated beyond high school, and 80% were married. METHODS: Adults were recruited
      from the county's randomly selected Superior Court jury pool. Jurors were
      approached by a researcher and asked to complete a self-administered
      questionnaire. MAIN RESEARCH VARIABLES: Parents' levels of sun-protection
      practices for themselves and their children, skin cancer knowledge, and skin
      sensitivity to sun; amount of health information parents received from healthcare
      providers, family and friends, schools, employers, and the media; and parents'
      perceptions of the information's accuracy, utility, and comprehensibility.
      FINDINGS: Parents are more likely to practice skin cancer prevention for their
      children than themselves. Parents' own protection is positively related to
      protection for children. Parents who were knowledgeable about skin cancer
      prevention received the most information from healthcare providers and family and
      friends. Parents who more frequently received information from healthcare
      providers practiced more prevention strategies. CONCLUSIONS: Parents need to
      improve their practices of protecting their children from the sun, particularly
      by limiting their sun exposure and having them wear protective clothing.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses in schools, work sites, and healthcare
      organizations should be active in skin cancer prevention. Nurses can teach
      parents that children are at risk, encourage parents to teach children to protect
      themselves, and address barriers to prevention.

PMID- 8577625
TI  - Information for women: management of menopausal symptoms.
AB  - PURPOSE/OBJECTIVES: To provide a written reference for women experiencing
      menopause-related symptoms. DATA SOURCES: Professional and popular books and
      articles. DATA SYNTHESIS: The process and symptoms of menopause are described in
      simple terms. Hormone replacement therapy is presented in terms of benefits and
      risks. CONCLUSIONS: A booklet is an easy-to-produce, efficient strategy for
      addressing common patient concerns. IMPLICATIONS FOR NURSING PRACTICE: A written
      booklet can assist nurses in presenting the necessary information to women
      experiencing or at risk for experiencing symptoms of menopause and in counseling
      them about potential interventions.

PMID- 8577626
TI  - Care of patients undergoing chemoembolization.

PMID- 8577627
TI  - Fictional character helps children cope with alopecia.

PMID- 8577628
TI  - Nurse-administered boluses enhance comfort at the end of life.

PMID- 8577629
TI  - Overview of cost-consequence modeling in outcomes research.
AB  - Outcomes research has developed in response to the need for information on costs,
      risks, and benefits of clinical treatments, including data regarding the
      effectiveness of prescription drugs. It attempts to consider more than the
      biologic effects of pharmaceuticals, that is, to encompass wider measures of the
      results of their use, issues that are not routinely addressed during clinical
      trials. Cost-effectiveness analysis compares the outcome of different treatment
      options in terms of monetary cost per unit of effectiveness. Examples of measures
      of effectiveness are years of life saved, number of days of hospitalization
      avoided, and number of treatment successes. Cost-consequence models, also
      referred to as cost-outcome models, deal with costs and a variety of outcomes
      ranging from clinical to humanistic. Direct medical costs are those for
      prevention, detection, treatment, and rehabilitation; they are amounts spent to
      treat an illness, including hospitalization, professional services,
      pharmaceuticals, and medical supplies. Indirect medical costs are associated with
      changes in productivity, such as earnings lost because of illness. Humanistic
      outcomes deal primarily with functional status, quality of life, and
      satisfaction, and may include pain, anxiety, self-esteem, ability to carry out
      normal activities, and overall impressions. Since it is not possible to study all
      effects of treatments with clinical trials, modeling techniques are useful in
      making therapeutic decisions.

PMID- 8577630
TI  - Management of herpesvirus infections in the healthy host.
AB  - Human herpesvirus infections continue to be a concern in immunocompetent as well
      as immunocompromised hosts. They are often life threatening in the
      immunocompromised patient. In the healthy immunocompetent person the infections
      tend to be self-limited, although they can directly or indirectly cause periods
      of severe discomfort and disability, and their treatment can affect productivity,
      as shown by cost-outcome models. Treatment of primary or secondary episodes in
      the immunocompetent host is therefore directed toward more rapid resolution of
      initial and recurrent episodes, thereby limiting the impact of the infections.

PMID- 8577631
TI  - Cost-consequence models for varicella-zoster virus infections.
AB  - Three cost-consequence models were developed for treatment of infections due to
      varicella-zoster virus (VZV) with acyclovir in immunocompetent patients--adult-
      and childhood-onset chickenpox, and herpes zoster (shingles) in adults. For
      chickenpox, separate models allow examination of differences in severity and
      impact of the disease for children and adults, as well as in the management of
      civilians and adults in military service. Each model includes direct medical
      costs, indirect costs and health-related productivity loss, symptom and quality
      of life impact, and model assumptions and conclusions. Alternatives of treatment
      and no treatment are addressed. Quality of life impact is conceptualized in terms
      of a quality-adjusted life-days decrement due to VZV symptoms of importance to
      the patient, such as pain, rash, and itching. As experience and data become
      available, alternative agents such as valacyclovir and famciclovir for the
      treatment of patients with herpes zoster should be included in the modeling
      process.

PMID- 8577632
TI  - Use of cost-consequence models in managed care.
AB  - Functioning effectively as a pharmacy benefit manager has been defined as
      purchasing the best product at the lowest possible cost. In the simplest terms,
      this means purchasing discounted drugs; in the most complex terms, it means
      managing drug use. However, if the entire medical picture were analyzed, use of
      more expensive drugs might actually lower total direct medical costs. Currently,
      formulary decisions are based on both therapeutic necessity and cost. The
      decision to administer one drug rather than another is directed by community
      practice patterns and the final price. The availability of information to
      demonstrate differences, if any, in total treatment costs between the two agents
      would considerably enhance therapeutic decision making and would guide treatment
      by an outcome-based drug formulary. The question that requires an answer is
      centered on the value equation: Value = outcomes/cost. Before paying more for
      drug A than for drug B, the payer will demand to see value. When available,
      direct and indirect cost information will be applied to position drugs
      appropriately in a drug formulary.

PMID- 8577633
TI  - Calcipotriol: a new drug for topical psoriasis treatment.
AB  - Vitamin D is best known for its role in the regulation of calcium and bone
      metabolism. The effects of the biologically active form of vitamin D, 1,25
      dihydroxyvitamin D3 (1,25 (OH)2D3), are mediated by binding to a specific
      intracellular vitamin D receptor, which is present in most tissues including the
      skin where it regulates the growth of epidermal cells. Calcipotriol is a
      synthetic analogue of 1,25(OH)2D3. In vitro the activity of calcipotriol is
      comparable to that of 1,25(OH)2D3. In vivo, however, the risk of calcipotriol
      changing calcium metabolism is greatly reduced. Animal studies have established
      that calcipotriol is 100-200 times less calcaemic than 1,25(OH)2-D3. This low
      calcaemic activity is mainly due to the rapid metabolism of calcipotriol. This
      pharmacological profile makes calcipotriol an ideal candidate for topical
      treatment of hyperproliferative skin disorders, such as psoriasis. This paper
      reviews the clinical experience with calcipotriol in psoriasis patients.

PMID- 8577634
TI  - Microsomal function in hepatitis B surface antigen healthy carriers: assessment
      of cytochrome P450 1A2 activity by the 14C-caffeine breath test.
AB  - The hepatitis B surface antigen (HBsAg) carrier state is associated with changes
      in hepatocellular function involving the cytochrome P450 (CYP) system. Among this
      system, CYP1A2 enzyme plays an important role in chemical carcinogenesis and in
      the metabolism of several drugs. We have thus investigated CYP1A2 function using
      two 14C-caffeine breath tests (3-methyl-14C; C3BT and 7-methyl-14C caffeine;
      C7BT) in 12 HBsAg healthy carriers and 8 healthy volunteers matched for 14C
      aminopyrine breath test values. HBsAg carriers exhibited lower C3- and C7BT
      values than normal controls. This difference, however, did not reach statistical
      significance except for C7BT values normalised for aminopyrine breath test
      values. Our data thus do not support the association between viral presence and
      CYP1A2 dysfunction.

PMID- 8577635
TI  - Prevention of class III-induced proarrhythmias by flecainide in an animal model
      of the acquired long QT syndrome.
AB  - The influence of the class Ic agent, flecainide, on the incidence of class III
      induced torsades de pointes was examined in an animal model of the acquired long
      QT syndrome. Twenty-four chloralose-anaesthetized rabbits were pretreated at
      random with flecainide or vehicle and subsequently given a concomitant infusion
      of methoxamine and the class III antiarrhythmic agent almokalant. In seven out of
      eight vehicle-treated rabbits, almokalant induced torsades de pointes which was
      preceded by a significant lengthening of the JTU interval (used as an indirect
      measure of ventricular repolarization time) by 55 +/- 9.2 msec. Flecainide dose
      dependently reduced the incidence of almokalant-induced torsades de pointes.
      Hence, in a group of rabbits given a low dose (0.14 mumol/kg + 1.4 mumol/kg/hr)
      of flecainide, four out of eight animals experienced torsades de pointes (P =
      0.1538 versus vehicle) whereas no case (n = 8) was observed after a higher dose
      (4.8 mumol/kg + 4.8 mumol/kg/hr, P = 0.0007). In the former group almokalant
      induced a maximal increase in the JTU interval not differing from that seen in
      the vehicle-treated group (58 + 12.1 msec, P > 0.05). Pretreatment with the high
      dose of flecainide, however, caused a significant attenuation of the almokalant
      induced lengthening of the JTU interval (18 +/- 6.5 msec. P < 0.05). It is
      concluded that flecainide reduces the risk of proarrhythmia in the setting of
      delayed repolarization partially by attenuating the primary electrophysiological
      effect of class III agents.

PMID- 8577636
TI  - Effects of misoprostol on circulating HDL-cholesterol, total cholesterol,
      triglycerides and their relationship with hepatic microsomal function.
AB  - The effects of misoprostol (cytotec, SC29333) on circulating lipoproteins and
      liver microsomal enzyme activity were studied. Misoprostol increased serum levels
      of high density lipoprotein-cholesterol and decreased total cholesterol and
      triglycerides. The high density lipoprotein-cholesterol/total cholesterol ratio
      increased by 54.8%. In parallel, misoprostol significantly altered enzyme hepatic
      activity. Liver microsomal cytochromes P450 and b5 were significantly increased
      in correlation with enhanced liver aminopyrine N-demethylase and antipyrine
      hydroxylase activities, suggesting a liver induction effect of misoprostol. Other
      observations such as increased liver weight and glycogen and increased plasma
      albumin and glucose in rats receiving misoprostol support this evidence.

PMID- 8577637
TI  - Estimation of the convulsive effect of cyanide in rats.
AB  - Convulsions are frequently observed in severe, acute cyanide intoxication. The
      mechanisms involved are not well known. In the present study, the convulsive
      effect of cyanide was examined in the rat by means of a dose threshold
      determination after infusion of cyanide. An optimal dose rate of 1.80 mg/min./kg
      was determined. By infusing this optimal dose rate it was possible to divide
      another cyanide-treated group of rats into two groups: one without and another
      with convulsions. After the experiment all animals were killed by exposure to
      high intensity microwave irradiation. Regional dopamine, noradrenaline and main
      dopamine metabolites were isolated and analyzed using high pressure liquid
      chromatography and electrochemical detection. Striatal noradrenaline was
      decreased but dopamine and its metabolites were increased in rats infused with
      cyanide at the optimal dose rate until the convulsions started. Animals infused
      with the threshold dose at the optimal dose rate did not show any significant
      changes in noradrenaline or in dopamine metabolites, but all animals showing
      convulsions also had increased striatal dopamine levels. Thus changes in dopamine
      appear to be dependent on convulsions.

PMID- 8577638
TI  - [3H]dexamethasone binding activity in liver microsomes is modulated differently
      by 17 alpha-alkylated androgens and testosterone in vivo.
AB  - Rat liver microsomes contain a single class of steroid binding sites, capable of
      binding various glucocorticoids and progesterone. In a previous article, we have
      described the in vitro interaction of several androgens with this binding site.
      Unlike natural androgens, the 17 alpha-alkyl derivatives stanozolol and danazol
      were capable of interacting with this binding site through a negative allosteric
      pattern. Now, the effects these steroids exert on the microsomal
      [3H]dexamethasone binding site have been studied in vivo. The administration of a
      single dose of stanozolol to rats provoked a significant reduction in the
      microsomal [3H]dexamethasone binding capacity. This effect was maximal two hr
      after stanozolol administration and persisted for six hr. The restoration of the
      [3H]dexamethasone binding level after stanozolol administration was dependent on
      protein synthesis, since it was blocked by the concomitant administration of
      cycloheximide. None of the other androgens tested (danazol, methyltestosterone,
      fluoxymesterone, and testosterone propionate) was capable of provoking a similar
      effect when administered 2 or 24 hr prior to sacrifice. In rats treated for seven
      days with a daily dose of diverse androgens and sacrificed 24 hr after the last
      treatment, none of the 17 alpha-alkyl androgens assayed provoked significant
      changes in the microsomal [3H]dexamethasone binding level, although stanozolol,
      danazol, and methyltestosterone provoked a significant increase in glucocorticoid
      receptor concentration. In contrast, the administration of testosterone
      propionate provoked a 50% reduction in the [3H]dexamethasone binding level
      without causing changes in the glucocorticoid receptor concentration. These
      results provide new evidence on the existence of different effects on the liver
      of 17 alpha-alkyl androgens, compared to the effects produced by natural
      androgens.

PMID- 8577639
TI  - Altered cAMP response after isoprenaline stimulation of mononuclear leucocytes
      from insulin-dependent diabetic patients with hypoglycaemia unawareness.
AB  - Loss of adrenergic hypoglycaemic symptoms is the most distinctive feature in
      insulin-dependent diabetes mellitus (IDDM) patients with hypoglycaemia
      unawareness. Previous reports from in vivo studies show reduced heart rate
      responsiveness both to adrenergic agonists and antagonists in these patients.
      This study was carried out to investigate whether the reduced adrenergic
      sensitivity in IDDM patients with hypoglycaemia unawareness (IDDM-unaware) also
      could be demonstrated as reduced increase in cAMP production in mononuclear
      leucocytes induced by isoprenaline stimulation, or reduced inhibition by ICI
      118551 (a selective beta 2-adrenergic receptor blocker) of isoprenaline induced
      cAMP production. We found that the slope of the concentration-response curves of
      isoprenaline/cAMP and the maximal cAMP concentrations obtained after isoprenaline
      stimulation were reduced in IDDM-unaware compared to control and IDDM patients
      with normal hypoglycaemia awareness (IDDM-aware). We did not find any significant
      differences in the response to ICI-118551 between control, IDDM-aware and IDDM
      unaware. This study supports the reports of reduced sensitivity of adrenergic
      agonists as a part of the pathophysiological changes in hypoglycaemia
      unawareness, but we have not been able to confirm the reports of an association
      between hypoglycaemia unawareness and reduced effect of adrenergic antagonists.

PMID- 8577640
TI  - Effect of p-chlorophenylalanine and alpha-methyltyrosine on the antinociceptive
      effect of antidepressant drugs.
AB  - The role of para-chlorophenylalanine and alpha-methyl-DL-p-tyrosine in the
      antinociceptive effects of the intracerebroventricular administration of the
      antidepressant drugs clomipramine, zimelidine, imipramine and maprotiline was
      studied using the acetic acid writhing test in mice. The results demonstrated an
      antinociceptive effect for all these antidepressants. Pretreatment with para
      chlorophenylalanine significantly reduced the antinociception induced by the
      ED50's of imipramine and maprotiline, and did not modify the effects of
      zimelidine and clomipramine, pretreatment with alpha-methyl-tyrosine did not
      modify the antinociception induced by these drugs except maprotiline.
      Pretreatment with para-chlorophenylalanine plus alpha-methyltyrosine
      significantly reduced the antinociceptive effect of all the antidepressants
      tested. The main finding of the present study is that the association of para
      chlorophenylalanine plus alpha-methyltyrosine reduced the antinociceptive action
      of all the antidepressants. This means that critical levels of both 5-HT and NA
      are responsible for mediating the antinociceptive effects of antidepressants on
      the writhing test in mice.

PMID- 8577641
TI  - 3,3',4,4'-tetrachlorobiphenyl effects on antioxidant enzymes and glutathione
      status in different tissues of rainbow trout.
AB  - Polychlorinated biphenyls are known to cause induction in cytochrome P450
      dependent monooxygenase activities and alteration in the antioxidant defense of
      mammals. To determine whether similar detoxication processes are activated in
      rainbow trout (Oncorhynchus mykiss), we investigated P450-dependent enzyme
      activities, antioxidant enzymes and glutathione status (reduced and oxidized
      glutathione, GSH and GSSG) in this species injected intraperitoneally with
      3,3',4,4'-tetrachlorobiphenyl at 5 mg/kg body weight 6 weeks post injection.
      Ethoxyresorufin O-deethylase activities increased 11- and 40-fold in liver and
      kidney. UDPglucuronosyltransferase activities were 2- and 5-fold higher in these
      organs, while glutathione S-transferase activity was enhanced greater than 2-fold
      in liver of tetrachlorobiphenyl injected trout in comparison with controls.
      Glutathione peroxidase activities were increased in liver and white muscle of
      dosed fish. Tetrachlorobiphenyl exposure resulted in a significant increase in
      glutathione reductase activities, with 7-fold enhancement in liver and
      significantly elevated activities in kidney, red and white muscles. Similarly,
      cytosolic superoxide dismutase and catalase activities were increased in white
      muscle of injected trout. Tetrachlorobiphenyl exposure significantly increased
      GSH concentrations in liver and kidney, while GSSG levels were increased in liver
      and blood plasma. These changes, however, did not modify the GSSG/GSH ratios in
      these tissues. Overall, these results imply a major tetrachlorobiphenyl effect on
      GSH status and antioxidant enzymes in trout tissues and identify white muscle
      along with liver and kidney as important tissues in the detoxication process in
      this animal.

PMID- 8577642
TI  - Cassia senna inhibits mutagenic activities of benzo[a]-pyrene, aflatoxin B1,
      shamma and methyl methanesulfonate.
AB  - Ethanol extract of Senokot tablets (Cassia senna concentrate used as vegetable
      laxative), was found to be non-mutagenic while it inhibited the mutagenicity of
      benzo[a]pyrene, shamma, aflatoxin B1 and methyl methanesulfonate in the Ames
      histidine reversion assay using the Salmonella typhimurium tester strain TA98.
      While the Senokot extract completely inhibited the mutagenicity of promutagens
      (i.e. metabolic activation dependent) like benzo[a]pyrene and shamma, it reduced
      the mutagenic activity of the direct acting mutagen methyl methanesulfonate by
      only 58%. The mutagen aflatoxin B1 showed a 25-fold increase in the number of
      histidine revertants per plate at low concentrations (1.0-4.0 micrograms/plate)
      in the presence of metabolic activation system while at high concentrations (10.0
      30.0 micrograms/plate) it proved to be weakly mutagenic (with a 5-fold increase
      in the number of histidine revertants/plate) without metabolic activation. The
      Senokot extract completely inhibited the mutagenic effect of low concentrations
      of aflatoxin B1 in the presence of metabolic activation but not that resulting
      from higher concentrations without metabolic activation. The results obtained
      with benzo[a]pyrene, shamma and aflatoxin B1 indicated that the antimutagenic
      effects of Senokot extract could be largely due to an interaction with the
      metabolic process involved in the activation of procarcinogens. However, the
      results obtained with methyl methanesulfonate suggested that factors in Senokot
      may also interact with direct mutagens to produce some antimutagenic effects. An
      ethanol extract of crude senna leaves found to be weakly mutagenic also inhibited
      (though less than Senokot) the mutagenic effect of benzo[a]pyrene suggesting that
      the antimutagenic principle is present in the complex plant material itself.

PMID- 8577643
TI  - Proliferation of hepatocytes and attenuation from carbon tetrachloride
      hepatotoxicity by gadolinium chloride in rats.
AB  - Intravenous injection of gadolinium chloride (GdCl3) at a dose of 10 mg/kg caused
      an increase in proliferating cell nuclear antigen labeling index and the grade of
      pyronin positivity (RNA level) in rat liver. In CCl4-exposed rats, pretreatment
      with GdCl3 also showed a preventive effect of the liver injury both biochemically
      and histologically. Moreover, the proliferative action preceded the attenuative
      effect of the liver injury. Results suggest that GdCl3 induces hepatocyte
      proliferation, and this action of GdCl3 may modify the development of CCl4
      induced liver injury.

PMID- 8577644
TI  - Effects of seed treatments and storage on the changes in lipids of pearl millet
      meal.
AB  - Lipids in pearl millet meal showed a rapid hydrolytic decomposition during
      storage. The magnitude of such degradation was influenced significantly by the
      nature of the storage container used, the temperature and heat treatments given
      to the seeds. The hydrolytic breakdown of lipids was significantly low in the
      meals stored in polyethylene bags, plastic boxes and under refrigerated (5 +/- 2
      degrees C) conditions. Hot water blanching at 98 degrees C for 10 sec and dry
      heating of seeds at 100 degrees C for 120 min were found to be most effective in
      minimising the undesirable changes in lipids of the meal during storage.

PMID- 8577645
TI  - Effect of dietary fibre from cereal brans and legume seedcoats on serum lipids in
      rats.
AB  - The present investigation was carried out to study the hypolipidemic effect of
      dietary fibre from cornbran and blackgram seedcoat in rats. Isoproteinous diet
      having one percent cholesterol and ten percent dietary fibre from cornbran and
      blackgram seedcoat was fed to four groups of albino rats for six weeks. With
      consumption of both the grain husks, total lipids, cholesterol and tryglycerides
      were lowered while HDL-cholesterol was found to be significantly increased.
      However, serum phospholipids were not affected significantly by grain husks.
      Cornbran was observed to be more hypolipidemic than blackgram seedcoat.

PMID- 8577646
TI  - Effects of processing and in vitro proteolytic digestion on soybean and yambean
      hemagglutinins.
AB  - Some conventional processing methods were applied on yambean and soybean seeds
      and flour samples. They include soaking fermentation, cooking whole seeds in the
      presence and absence of trona, autoclaving and dry heat treatment of flour
      samples. Hemagglutinating activity was assayed for after processing treatments.
      The hemagglutinating proteins from these seeds were classified based on their
      solubility properties. Effects of the presence of 0.01% concentration of trypsin,
      pepsin and proteases on agglutination of human red blood cells were also
      evaluated. Most processing methods, particularly cooking whole seeds for 1-2 h,
      soaking and fermentation, reduced hemagglutinating activity on cow red blood
      cells. Size reduction accompanied by heat treatment was effective in eliminating
      hemagglutination. Both the albumin and globulin fractions of the soybean showed
      hemagglutinating activity but only the albumin fraction of the yambean had
      agglutinating properties. Proteolytic action of proteases was more effective in
      reduction of hemagglutinating activity than that of trypsin and pepsin.

PMID- 8577647
TI  - Nutritive value evaluated on rats of new cultivars of common beans (Phaseolus
      vulgaris) released in Chile.
AB  - Five new cultivars of common beans (Phaseolus vulgaris) recently released were
      analyzed for their proximate chemical composition and protein biological quality.
      The crude protein content in these cultivars ranged from 21.9 percent in cultivar
      Arroz 3 to 26.9 percent in cultivar Tortola Diana (dry matter basis). Rats fed
      cultivar Tortola INIA gained more weight, had a higher protein intake and
      registered higher PER and NPR than Tortola corriente. On the other hand, rats
      consuming cultivars Arroz 3 and Fleetwood had lower weight gain, lower protein
      intake and lower PER and NPR than cultivar Coscorron corriente. However, all
      these cultivars have a relatively good protein value as compared to other plant
      protein sources.

PMID- 8577648
TI  - Cereal and nut bars, nutritional quality and storage stability.
AB  - Six snack-type bars were manufactured, to contain oat and wheat germ and two
      different walnut levels, agglutinated with natural sweeteners and fats. Two bars
      also contained toasted amaranth with brown sugar cover and wheat extrudate, while
      two others, contained puffed instead of toasted amaranth. Water activity (Aw) and
      moisture were determined in the manufactured products. Quality and sensory
      evaluation and proximate analysis were carried out on the bars containing highest
      levels of walnuts (18%). The caloric contribution of the bars was computed by
      Atwater methods. The nutritional quality of the bars was determined by means of
      the Protein Efficiency Ratio (PER) and Net Protein Ratio (NPR), and the results
      were used to obtain relative PER and relative NPR. Samples of the latter bars
      were kept under accelerated storage for 15 days at 37 degrees C and analyzed
      every 5 days to determine their Aw, moisture, peroxide and sensory acceptability.
      The drying time for the cereal - and walnut - based bars was 45 min at 120
      degrees C. All bars presented a good fiber supply and the CN1 bar, containing
      only oat, wheat germ and walnut, had the greatest protein content. In the sensory
      evaluation, the walnut level with the greatest preference was 18%. PER and NPR
      values of the bars did not differ significantly showing values approximately 86%
      that of the casein value. During storage, the moisture and Aw decreased in all
      the bars. Peroxides remained within the acceptable ranges; acceptability based on
      sensory evaluation remained best in the bar with toasted amaranth.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8577649
TI  - The nutritive quality of maize-soybean (70:30) tempe flour.
AB  - The nutritive quality of maize-soybean (70:30) tempe flour manufactured by
      fermentation with Rhizopus oligosporus: Rhizopus orysae (1:1) was determined
      using weanling rats. Mould fermentation of maize-soybean mixture did not
      significantly affect its proximate composition. It increased the content of
      reducing sugars, total acids and aminonitrogen by about 43, 195 and 482 percent,
      respectively, and decreased phytate content by 46 percent. In vitro iron
      absorption for maize flour and maize-soybean tempe flour was 2.46 and 5.51
      percent, respectively. Protein Efficiency Ratio (PER) and Net Protein Ratio (NPR)
      for maize-soybean tempe flour and skim-milk diets were 2.71 and 2.96,
      respectively, for PER, and 3.31 and 3.51, respectively, for NPR. In vivo protein
      digestibility of the two products was 95.0 and 98.0 percent, respectively.

PMID- 8577650
TI  - Studies on samh seeds (Mesembryanthemum forsskalei Hochst) growing in Saudi
      Arabia, 1: Anatomy of Samh seed.
AB  - The seeds of Samh (Mesembryanthemum forsskalei) are 'Ostensibly Campylatropous'
      as they seem externally anatropous but internally they have a curved embryo and
      both the seed body and the funicle exchange shapes. The embryo occupies a
      cylindrical seed body and is surrounded by a thin layer of endosperm; the major
      part of the endosperm occupies an ovoid bulge resembling a seed body.

PMID- 8577651
TI  - Comparative nutritive value of winged bean (Psophocarpus tetragonolobus (L) DC)
      and other legumes grown in Tanzania.
AB  - Chemical analyses and feeding experiments using rats were conducted to evaluate
      the nutritive value of winged bean and other legumes (soyabean, green gram,
      bambarra nuts, pigeon peas, field beans, cow peas) sources grown in Tanzania.
      Proximate analyses showed that the composition of winged bean was similar to
      soyabean, while the composition of the other legumes differed considerably. This
      was also the case for antinutritional constituents and minerals. As to the amino
      acid composition, the lysine level was high with the highest value in winged bean
      (7.5 g/16 g N). However, the concentration of methionine and cystine was low
      which limits their protein quality. Another important amino acid, threonine, was
      generally high, especially in winged bean (4.3 g/16 g N). With exception of field
      bean, true protein digestibility was above 80%, soyabean having the highest value
      (90.7%). The biological value was also highest in soyabean (76.1%) followed by
      winged bean (69.9%). Utilizable protein was high in soyabean (28.8%) and somewhat
      lower in winged bean (23.4%). Energy digestibility was around 80%, soyabean
      having the highest value of 85.8%. The study findings support the idea that
      winged bean is a good alternative plant protein source in Tanzania.

PMID- 8577652
TI  - Elaboration of amylase activity and changes in paste viscosity of some common
      Indian legumes during germination.
AB  - The effect of germination upto 120 hours on malting loss, amylase activity and
      viscosity of nine common Indian legumes was investigated. The amylase activity
      increased on progressive germination in all legumes, the increase being
      particularly high for green gram, horse gram, moth bean and black gram. Malted
      samples had lower cooked paste viscosity than native ones. Samples with high
      amylase activity exhibited proportionately lower viscosity. Maximum reduction in
      viscosity was observed in green gram, followed by moth bean, horse gram, black
      gram and cowpea within 48 hours of germination. Malting losses ranged between 12
      to 27 percent over a period of 48 hours in all legumes. Germination beyond 48
      hours resulted in considerably higher malting losses without much effect on
      viscosity.

PMID- 8577653
TI  - Influence of vegetative cycle of asparagus (Asparagus officinalis L.) on copper,
      iron, zinc and manganese content.
AB  - The essential elements copper (Cu), iron (Fe), zinc (Zn) and manganese (Mn) were
      analyzed in fresh asparagus to determine the effects of the vegetative cycle of
      the plant on the micronutrient content. Asparagus samples were classified in two
      groups by diameter (< 11 mm and > 14 mm). Asparagus from a sample group with the
      same diameter were divided into two portions (apical and basal) according to
      distance from the tip. The concentrations of copper, iron, zinc and manganese
      increased during the vegetative cycle of the asparagus, mainly in the apical
      portion which showed significantly greater concentrations with respect to the
      basal portion. The > 14 mm diameter asparagus presented higher levels of copper,
      zinc and manganese, whereas the concentration of iron was greater in the < 11 mm
      diameter asparagus. The mean element levels were (mg/kg dry weight): Cu, 18.9 +/-
      3.9; Fe, 91.7 +/- 33.7; Zn, 69.5 +/- 24.6 and Mn, 20.9 +/- 5.0).

PMID- 8577655
TI  - Effect of blanching on the content of antinutritional factors in selected
      vegetables.
AB  - The effect of blanching on the antinutritional content was studied in cabbage,
      turnip, collard, sweetpotato and peanut leaves. All the vegetables contained
      various amounts of phytic acid, tannic acid and/or oxalic acid. Tannic acid was
      found in largest amounts ranging from 1266.00 mg/100 g in cabbage to 491.00
      mg/100 g in sweetpotato. Phytic acid content ranged from 0.31 mg/100 g in
      sweetpotato to 3.97 mg/100 g in collard. Oxalic acid was in trace amounts in
      cabbage and turnip; but high concentrations were found in sweetpotato (469.67
      mg/100 g) and peanut greens (407.00 mg/100 g). Levels of both tannic acid and
      phytic acid were significantly (p < 0.05) reduced by conventional and microwave
      blanching methods while oxalic acid levels were not significantly (p < 0.05)
      reduced in most of the treatments by either of the blanching methods. In general,
      blanching is recommended as an effective method for reducing the antinutritional
      factors in green vegetables, however, further investigation on the heating times
      for both conventional and microwave blanching methods has been suggested.

PMID- 8577654
TI  - Trace elements in spinach (Spinacia oleracea) cultivated in soil fortified with
      graded levels of iron.
AB  - Trace elements in two varieties of spinach cultivated in soil with different
      levels of added iron were determined. Addition of iron to soil decreased
      potassium, sodium and magnesium contents in spinach markedly (p < 0.05), while
      the contents of zinc, manganese and copper in spinach were not significantly
      altered (p > 0.05). Differential behavior of spinach varieties was found in the
      zinc, manganese and sodium contents.

PMID- 8577656
TI  - Current topic: HLA and reproduction: lessons from studies in the Hutterites.
AB  - The paradoxical observation that maternal-fetal incompatibility with respect to
      human leucocyte antigen (HLA) genes was not associated with spontaneous abortion,
      stillbirths or developmental abnormalities led to the hypothesis that fetuses
      with paternally-derived HLA that differ from maternal HLA may enjoy a selective
      advantage during pregnancy. If true, then couples who share HLA should experience
      poorer reproductive outcome than couples not sharing HLA. Numerous, retrospective
      studies of parental HLA sharing and fetal wastage in humans have yielded
      conflicting results and discrepancies are difficult to reconcile because of
      methodological differences among studies and potential heterogeneity among
      subjects. To explore the hypothesis that maternal-fetal HLA compatibility is
      deleterious in human pregnancy, we initiated prospective and population-based
      studies in the Hutterites, a religious isolate that lives communally and
      proscribes contraception. Our data suggest that HLA-DR-linked genes may affect
      fertilization or implantation and HLA-B-linked genes may contribute toward
      recognized fetal loss. Discrepant results among retrospective studies of outbred
      couples may be due to the fact that more than one HLA region influences
      reproductive outcome and that the genes influencing fertility may not be HLA
      genes per se, but loci in linkage disequilibrium with HLA-B and HLA-DR.

PMID- 8577658
TI  - Beta-adrenergic regulation of cyclic AMP synthesis in cultured human
      syncytiotrophoblast.
AB  - Isolated elements of the beta-adrenergic/adenyl cyclase signal transduction
      system have been studied previously using purified membranes. We used cultured
      syncytiotrophoblast cells to identify components of this signalling system and
      the interactions which regulate syncytial adenyl cyclase. Generation of cyclic
      AMP (cAMP) was stimulated in these cells by both forskolin and isoproterenol but
      not by dopamine, adenosine, carbachol or prostaglandin E1. Synthesis was also
      stimulated by treatment with cholera toxin, indicating the involvement of the G
      protein, Gs. Somatostatin inhibited isoproterenol- or forskolin-stimulated cAMP
      generation, an effect which could be blocked by pretreatment of the cells with
      pertussis toxin, demonstrating the mediation of somatostatin action by Gi.
      Furthermore, secretion of human chorionic gonadotrophin (hCG) was increased
      significantly by isoproterenol while somatostatin blocked the isoproterenol
      stimulated release of hCG. These results clearly demonstrate that adenyl cyclase
      in syncytiotrophoblast is controlled by a stimulatory pathway operating through
      Gs and inhibitory pathway acting through Gi.

PMID- 8577657
TI  - Expression of cell adhesion molecules in placentae from pregnancies complicated
      by pre-eclampsia and intrauterine growth retardation.
AB  - Platelets and neutrophils are involved in maternal placental vascular damage in
      pre-eclampsia. Recruitment of these cells is probably mediated by cell adhesion
      molecules expressed at the uteroplacental bed. It remains controversial as to
      whether platelets and neutrophils mediate damage to trophoblast or villous
      vasculature. The purpose of this study was to determine the expression of cell
      adhesion molecules in placentae from normal pregnancies and pregnancies
      complicated by pre-eclampsia and intrauterine growth retardation (IUGR).
      Immunostaining for platelet endothelial cell adhesion molecule (PECAM) and
      intercellular adhesion molecule-1 (ICAM-1) was localized mainly to the
      endothelium of stem villi, intermediate villi, terminal villi and decidual
      vessels. Scattered staining for ICAM-1 was also evident in the stroma and fetal
      membranes. The endothelium of stem villi, intermediate villi and terminal villi
      were all negative for vascular cell adhesion molecule-1 (VCAM-1) and E-Selectin.
      PECAM, ICAM-1 and ICAM-2 mRNA were all detectable in normal placentae using
      northern blotting analysis whereas mRNA for E-Selectin and VCAM-1 were both
      undetectable. There were no differences in cell adhesion molecule immunostaining
      or mRNA expression in placentae from pregnancies complicated by pre-eclampsia and
      IUGR inconclusion, expression of cell adhesion molecules in placentae from pre
      eclampsia and IUGR are consistent with a normal physiological role in vascular
      function.

PMID- 8577659
TI  - Effect of human chorionic gonadotrophin on chloride current in human
      syncytiotrophoblasts in culture.
AB  - Human trophoblast differentiates in vivo and in vitro by the fusion of
      cytotrophoblastic cells to form syncytiotrophoblasts. A large amount of human
      chorionic gonadotrophin (hCG) is produced by the syncytiotrophoblasts, which
      express hCG luteinizing hormone (LH) receptors. Since recent investigations with
      electrophysiological techniques support the conclusion that hormonal effects can
      be mediated by modulations of the membrane ionic conductances of the cells, a
      perforated patch-clamp technique was used to investigate the possible presence of
      a chloride current evoked by hCG. The perifusion of hCG (500 mIU/ml) activated a
      time-independent current, which presents a linear current-voltage (I/V)
      relationship in symmetrical chloride concentrations. The reversal potential was 
      1.8 mV with 142 mM Cl- external solution and 134 mM cl- internal solution. This
      reversal potential shifted with changes in the transmembrane Cl- gradient.
      Moreover, this hCG-induced current was sensitive to 5-nitro-2-(3
      phenylpropylamino)benzoic acid (NPPB) (50 microM), to diphenylalamine-2
      carboxylic acid (DPC) (0.5 mM) and to 9-AC (1 mM), three known chloride channel
      blockers. These results confirm the autocrine action of hCG in the physiology of
      the trophoblast.

PMID- 8577660
TI  - Transport and metabolism of adenosine in the perfused human placenta.
AB  - Uptake and metabolism of adenosine by human placenta were studied using the
      single-circulation paired-tracer technique. When isolated cotyledons were
      perfused through the fetal (basal) circulation at mean pressures of 36 +/- 3.3
      mmHg and mean flow rates of 6.6 +/- 0.3 ml/min the maximal [3H]adenosine uptake
      was 51.3 +/- 3.9 per cent. The uptake was not changed when the vascular
      resistance was pharmacologically increased. Adenosine uptake was significantly
      inhibited by adenosine, inosine and nitrobenzylthioinosine (NBMPR), but was
      unaffected by hypoxanthine. The kinetic analysis of adenosine transport showed it
      to be a saturable and, Na(+)-independent process, with a Km of 60.8 microM and a
      Jmax of 0.148 mumol/min. Thin layer chromatographic analysis showed that about 65
      per cent of [3H]adenosine was metabolized (10-30 sec) in a single passage through
      the fetoplacental circulation. [3H]hypoxanthine and [3H]adenine were the major
      products recovered in the venous perfusate. In the presence of NBMPR the
      fractional recovery of [3H]adenine and [3H]phosphorylated derivatives was reduced
      while that of [3H]hypoxanthine was increased. These overall results show that the
      uptake of adenosine is a Na(+)-independent, NBMPR-sensitive, carrier-mediated
      process, which appears to be specific for nucleosides, and suggests that
      metabolization of adenosine proceeds both intra- and extracellularly.

PMID- 8577661
TI  - Quantitation and immunolocalization of glucose transporters in the human
      placenta.
AB  - The subcellular distributions of the mammalian passive glucose transporter
      isoforms GLUT1, GLUT3 and GLUT4, in the human placenta, were investigated using
      isoform-specific anti-peptide antibodies. On western blots of both basal and
      brush-border plasma membranes isolated from the syncytiotrophoblast, antibodies
      specific for GLUT1 labelled a broad band (apparent Mr 55,000) that co-migrated
      with the human erythrocyte GLUT1 glucose transporter. In contrast, no labelling
      was detectable when blots were probed with antibodies specific for the GLUT3 or
      GLUT4 isoforms. Densitometric analysis of blots showed that GLUT1 accounts for
      approximately 90 and 65 per cent of the D-glucose-sensitive cytochalasin B
      binding sites present in brush-border and basal membranes, respectively. Confocal
      immunofluorescence microscopy of fixed placental tissue showed that GLUT1 is
      abundant at both maternal- and fetal-facing surfaces of the syncytiotrophoblast
      whereas it was undetectable at the fetal capillary endothelium. In parallel
      experiments, no staining by antibodies against either the GLUT3 or the GLUT4
      isoforms was detected in placental tissue. These results indicate that GLUT1 is
      the major isoform responsible for glucose transfer from mother to fetus. The
      absence of GLUT4 is consistent with the lack of insulin-sensitive glucose
      transport across the placenta.

PMID- 8577662
TI  - Immunocytochemical localization of thioredoxin in human trophoblast and decidua.
AB  - An immunocytochemical investigation into the expression of thioredoxin in human
      reproductive tissues was performed using monoclonal antibodies produced against
      recombinant human thioredoxin. First trimester and term human placental villi,
      decidua and term fetal membranes were examined for thioredoxin content and
      cellular localization. In first trimester tissue strong thioredoxin staining was
      observed in the underlying cytotrophoblast cells and in the stromal cells present
      in the decidua, but not in the syncytiotrophoblast surrounding the chorionic
      villi. In term placental villi very little thioredoxin was observed. Term fetal
      membranes proved to be a rich source of thioredoxin, the most intense staining
      was seen in the cytotrophoblast cells in the chorionic membrane, with the amnion
      and decidua also showing positive immunoreactivity. The potential role/s that
      thioredoxin may play within the placental bed is considered.

PMID- 8577663
TI  - Isolation and characterization of a feeder-dependent, porcine trophectoderm cell
      line obtained from a 9-day blastocyst.
AB  - We have established in culture a feeder-dependent cell line, termed TE1, from a 9
      day, pre-implantation, porcine embryo. TE1 cells were observed by light and
      electron microscopy, and characterized by immunocytochemistry: the morphology,
      cytology and ultrastructure of this cell line are described. The cells display
      epithelial characteristics, as revealed using immunofluorescence microscopy with
      antibody against cytokeratins of simple epithelia, but not with antibody against
      vimentin. The cells demonstrate many morphological and cytochemical features in
      common with trophectoderm of the intact porcine blastocyst. For example, TE1
      cells are polarized and possess tight junctions at their borders, similar to
      those found in trophectoderm of the pre-implantation embryo. Moreover, TE1 cells
      label positively for the porcine trophectoderm-specific monoclonal antibody,
      SN1/38. Thus, by several important criteria TE1 is deduced to be a porcine
      trophectoderm cell line.

PMID- 8577664
TI  - Blood flow in the intervillous space in the first trimester.

PMID- 8577665
TI  - Conference report: 22nd Annual Meeting of the Society for the Study of Fetal
      Physiology, Malmo, Sweden, 11-14 June 1995.

PMID- 8577666
TI  - [Tuberculosis in Germany and the German Central Committee for the control of
      tuberculosis].

PMID- 8577667
TI  - [The worldwide status of tuberculosis today].

PMID- 8577668
TI  - [Mycobacteria and mycobacterioses].
AB  - The genus Mycobacterium harbours a number of significant pathogens. The diagnosis
      of mycobacterial infections has traditionally relied on microscopical and
      cultural techniques which were compromised by the slow growth of these
      microorganisms. More recently, molecular methods suitable for use in diagnostic
      microbiology have been developed and have been demonstrated to significantly
      improve both our diagnostic capabilities as well as our understanding of this
      complex genus of microorganisms.

PMID- 8577669
TI  - [Immunology of tuberculosis].
AB  - Protective immunity against Mycobacterium tuberculosis is mediated by specific T
      lymphocytes and executed by mononuclear phagocytes. The crosstalk between
      distinct T cell subsets and macrophages involves various cytokines. Attraction of
      blood monocytes to the site of mycobacterial replication and local macrophage
      activation result in granuloma formation. Interactions between T cell subsets and
      macrophages within granulomas enable the host to restrict mycobacterial growth,
      but only rarely cause sterile eradication. Therefore, at later time points,
      active tuberculosis may develop as a consequence of weakened immunity.

PMID- 8577670
TI  - [Therapeutic approaches in diseases caused by mycobacteria].
AB  - Following the historical introduction (the review by Schlossberger, 1928) the
      evolution of individual chemotherapy phases is briefly discussed. Then after
      following points are discussed. 1) The usual controlled clinical trials for
      evaluation of new drugs must be replaced (perhaps by estimates of the "early
      bactericidal activity" and of the 2 months' sputum conversion rates). 2)
      Interesting and of importance are research activities connected with the reasons
      for properties of TB bacilli in the persistence state, and of drugs capable to
      combat such bacilli (metronidazole?). 3) Since the human immunity against TB
      normally operates well (from 100 infected approximately 10 will get a clinically
      manifest disease), it is necessary to investigate possible combinations of chemo-
      and immunotherapy, either of combinations of antituberculous and immunomodulating
      drugs (eg. TNF alpha-antagonists), or of chemotherapy combined with vaccination
      (eg. M. vaccae). 4) There are still unsolved problems in formulations of drugs
      (particularly R in fixed combinations) and of drug resorption (in HIV-pos.
      patients). 5) Other points of research interest could be the adsorption of TB
      bacilli on the surface of mammalian cells (1st step in pathogenesis), drugs other
      than antituberculotics (eg. amoxycillin + clavulanic acid), or even drugs used
      for completely other diseases (eg. antidepressive). 6) All these attempts should
      serve primarily the purpose of further reduction of the necessary therapy
      duration (M+ pulmonary TB) to 1 - 2 months in total.

PMID- 8577671
TI  - Tuberculosis and HIV infection worldwide.
AB  - The incidence of HIV-associated tuberculosis is increasing worldwide and will
      continue to increase during the foreseeable future, especially in developing
      countries. HIV infection appears to increase the opportunity for M. tuberculosis
      to succeed in causing infection after inhalation into the lungs. Moreover, there
      is persuasive evidence that in the presence of HIV infection, new-onset
      tuberculous infection will progress rapidly to clinically significant disease and
      the likelihood that latent tuberculous infection will reactivate is enormously
      increased. The accelerating and amplifying influence of HIV infection is
      contributing to the increasing incidence of disease caused by multidrug-resistant
      strains of M. tuberculosis. Neither clinical or radiographic features reliably
      distinguish the majority of patients with HIV-associated tuberculosis from those
      who are non-HIV-infected. The remainder, however, may have atypical
      manifestations and be difficult to diagnose. Six months of chemotherapy with
      conventional antituberculosis drugs cures most patients, but many die during or
      after treatment of other AIDS-related complications.

PMID- 8577672
TI  - [Tuberculosis and radiologic diagnosis 100 years after W. C. Roentgen].
AB  - The discovery of the x-rays by W. C. Roentgen 100 years ago significantly
      improved the diagnosis and follow-up of tuberculosis, therapy control became
      possible, and the basis for prevention was set by early detection. Within few
      years, the "Roentgen" rays had been made a triumphant progress around the world,
      and Roentgenology was established as an independent medical discipline. Even
      after a century of developments like tomography, ultrasound, conventional/-high
      resolution and spiral computed tomography, digital radiography, digital
      subtraction angiography, and magnetic resonance imaging, innovations in the field
      of medical imaging appear to be unlimited, an evolution, which had been initiated
      by Roentgen. Today, therapists and radiologists are again challenged by the
      renaissance of tuberculosis, partially in new "clothes" by increasing numbers of
      HIV-patients. These specific changes clinically and radiological often appear
      atypical, and require subtile radiological diagnostics with the use of new
      imaging modalities. CT and MRI allow for follow-up of chemotherapy in mediastinal
      lymph node disease, significantly improve pleural diagnosis, and both are methods
      of choice in vertebral and cerebral tuberculous disease. Digital radiography and
      digital net-work allow for x-rays at the lowest dose, improved comparison in the
      follow-up, as well as for "online"-evaluation of images on the department's
      screen. Today, optimal diagnosis of tuberculosis includes the bacteriologic and
      clinical diagnosis and radiological imaging. To face the challenge of recurrent
      tuberculosis in in the second century after after Roentgen successfully, an
      intensive interdisciplinary cooperation of therapists and radiologists is
      necessary.

PMID- 8577673
TI  - Inactivation of p53 and the development of tetraploidy in the elastase-SV40 T
      antigen transgenic mouse pancreas.
AB  - Human pancreatic cancer develops in association with an acquired genomic
      instability, but the events that lead to instability are difficult to investigate
      because they occur sporadically and unpredictably. The elastase-SV40 T antigen
      transgenic mouse model of pancreatic adenocarcinoma reproducibly proceeds through
      a diploid --> tetraploid --> multiple aneuploid sequence of genetic
      abnormalities. We investigated the relationship between inactivation of p53 and
      development of tetraploidy in this model. Because T antigen inactivates p53 by
      forming a stable complex with it, we used multiparameter flow cytometry to assess
      p53 expression in pancreatic samples of transgenic and control mice between 8 and
      24 days of age. On day 18, a cell cycle-specific inactivation of p53 developed
      between diploid G, and S phase and was associated with the appearance of a
      cycling tetraploid cell population that had p53 protein overexpression in both G1
      and S-phase cells. Cytogenetic analysis of pancreatic samples confirmed the
      development of a tetraploid cell population. Inactivation of p53 in diploid cells
      of the transgenic pancreas is followed by the development of a tetraploid cell
      population. We have shown previously that this tetraploid intermediate is
      predisposed to progression to aneuploidy because it has abnormal mitotic poles.
      Therefore, our results suggest that inactivation of p53 by T antigen leads to
      formation of a tetraploid cell intermediate that is predisposed to chromosome
      segregation abnormalities and the development of multiple aneuploid cell
      populations.

PMID- 8577674
TI  - Coffee and cancer of the pancreas: an Italian multicenter study.
AB  - While cigarette smoking is a well-established risk factor for pancreatic cancer,
      the role of alcohol, coffee and tea consumption remains controversial. In view of
      this, and because of the limited information on possible environmental risk
      factors of pancreatic cancer in Italy, we carried out this study. Five hundred
      seventy patients with newly diagnosed pancreatic cancer and 570 controls from 14
      Italian centers were studied. Using a standardized questionnaire, all were
      interviewed personally about their smoking habits, as well as habitual alcohol,
      coffee, and tea consumption throughout their lives prior to clinical onset of the
      disease. Details were also obtained on exposure to potential occupational
      carcinogens. A moderate association, statistically significant only in women
      (odds ratio, 2.18; 95% confidence interval, 1.30-3.68), was found between
      pancreatic cancer and cigarette smoking, but none was observed with alcohol or
      tea consumption or with any particular occupational exposure. Consumption of 1 or
      2 cups of coffee per day was not associated with increased risk; 3 coffees per
      day increased the risk, but not significantly (odds ratio, 1.49; 95% confidence
      interval, 0.97-2.30); with consumption of more than 3 coffees per day the
      increase in risk was highly significant (odds ratio, 2.53; 95% confidence
      interval, 1.53-4.18). A statistically significant dose-response relationship (p <
      0.001) was observed in each sex. The association between coffee use and
      pancreatic cancer still held after controlling for potential confounding factors
      such as cigarette smoking or alcohol use, and when the analysis was restricted to
      nonsmoking coffee drinkers. The results of this study, one of the largest of its
      type so far published, suggest that a causal relationship may exist between
      coffee consumption and pancreatic cancer.

PMID- 8577675
TI  - Different implications of Ca2+i and and Ca2+e in CCK/gastrin-induced amylase
      secretion in AR4-2J cells.
AB  - The importance of Ca2+ in the regulation of secretion is well-known. However,
      recent experiments suggest that a rise in intracellular Ca2+ (Ca2+i) does not
      necessarily trigger secretion in pancreatic acinar cells. In AR4-2J cells the
      role of the Ca2+ mobilization induced by cholecystokinin/gastrin (CCK/G), which
      is dependent of the intracellular calcium store and the calcium influx operating
      through voltage-dependent calcium channels, has never been directly demonstrated.
      Therefore, we attempted to determine whether Ca2+i and/or extracellular Ca2+
      (Ca2+e) mobilized by CCK/G plays a role in the amylase secretion of these cells.
      We measured the [Ca2+]i by spectrofluorometry and amylase release in different
      experimental procedures modulating the two pools of calcium. Ionomycin increased
      both [Ca2+]i and amylase related. In Ca(2+)-depleted cells or in the presence of
      thapsigargin the transient rise in Ca2+i and the amylase secretion induced by
      CCK/G were suppressed. A 50 mM K+ solution or Bay K 8644, which activated the
      Ca2+ influx, did not induce any variation of the basal amylase secretion.
      Moreover, amylase secretion induced by CCK/G did not change significantly in
      Ca(2+)-free medium or in the presence of nifedipine. These results indicate that
      in AR4-2J cells, amylase secretion is dependent of the large increase in Ca2+i
      induced by CCK/G and independent of the Ca2+ influx through voltage-dependent
      calcium channels dihydropyridine sensitive.

PMID- 8577676
TI  - Calcium induces rapid changes in protein phosphorylation in permeabilized
      pancreatic acini.
AB  - Calcium is an important mediator of pancreatic stimulus-secretion coupling, and
      in streptolysin O-permeabilized acini maximal amylase release can be induced by 1
      microMCa2+. Two-dimensional analysis of acinar phosphoproteins using 32P-labeled
      acini showed that 1-min stimulation of permeabilized acini with 1 microMCa2+
      induced a number of rapid protein phosphorylation and dephosphorylation events
      similar to previously observed effects of secretagogues acting on intact acini.
      The rapid Ca2+ effects on protein phosphorylation correlated well with the
      earliest detectable onset of amylase release after 1 min of incubation with Ca2+.
      Our findings indicate that some of the agonist-induced changes in protein
      phosphorylation are mediated by Ca2+ and also provide evidence for the possible
      involvement of Ca(2+)-mediated dephosphorylation in acinar stimulus-secretion
      coupling.

PMID- 8577677
TI  - Androgen receptor in the rat pancreas: genetic expression and steroid regulation.
AB  - Androgens influence the incidence and prevalence of pancreatic cancer in humans
      and animal models. To our knowledge there has been molecular demonstration of the
      presence of neither the androgen receptor (AR) nor transcripts of the AR gene.
      Reverse-transcription polymerase chain reaction (RT-PCR)-Southern blotting was
      employed for molecular detection and measurement of the androgen receptor
      messenger ribonucleic acid (AR mRNA) in pancreas. Total RNA obtained from
      pancreas, prostate, seminal vesicles, and testes of neonatal and adult male and
      female rats, as well as castrated males substituted with testosterone
      cyclopentylate, was analyzed by Northern blot technique. Positive hybridization
      to AR cDNA was obtained in all tissues assayed but not in the pancreas. However,
      a clear AR 32P cDNA hybridization signal was obtained in pancreatic tissues after
      cDNA synthesis using RT-PCR-Southern blotting. The levels of the AR transcripts
      obtained by RT-PCR in the various pancreatic samples were as follows: adult
      females and neonatal animals > castrated adult males > adult males > castrated
      adult males substituted with testosterone. These results indicated that the
      pancreatic tissue possessed transcriptional activity of the AR gene, although to
      a lesser extent than the typical androgen responsive tissues (prostate and
      seminal vesicles). In conclusion, transcriptional activity of the AR gene in the
      pancreas seemed to be modulated by the androgenic milieu in the tissue similar to
      that reported for the classical androgen-responsive organs.

PMID- 8577678
TI  - Regulation of gene expression of pancreatic secretory trypsin inhibitor-61 and 
      56 by bile and pancreatic juice in rats.
AB  - The rat possesses two pancreatic secretory trypsin inhibitors (PSTI-61 and -56).
      PSTI-61 has been known to stimulate cholecystokinin (CCK) release, whereas PSTI
      56 did not. Both PSTIs are synthesized in the pancreatic acinar cells. CCK has a
      trophic effect on pancreatic acinar cells, and the exclusion of bile-pancreatic
      juice from the intestine has been known to be a most potent stimulator of CCK
      release. In the present study, we examined whether the mRNA levels of PSTI-61 and
      -56 produced by bile-pancreatic juice diversion were different from each other
      and compared the changes in CCK mRNA levels in the small intestinal mucosa and
      the plasma and intestinal CCK concentrations. Male Wistar rats were prepared with
      internal fistula and bile-pancreatic juice was excluded from the proximal
      intestine, being introduced into the distal ileum. Rats were sacrificed 1, 3, and
      7 days after the operation. The concentrations of plasma and intestinal CCK and
      the levels of mRNA of CCK in the intestinal mucosa and PSTIs in the pancreas were
      significantly increased by bile-pancreatic juice diversion. The increase in the
      mRNA level of PSTI-61 was significantly higher than that of PSTI-56.
      Administration of CCK antagonist inhibited these changes but administration of
      CCK agonist could not fully reproduce these changes. These studies suggest that
      bile-pancreatic juice regulates gene expression of CCK and PSTIs and that the
      regulatory mechanisms of gene expression of PSTI-61 and -56 may be different.

PMID- 8577680
TI  - Regulation of cyclic AMP levels in guinea pig pancreatic ducts and cultured duct
      epithelial monolayers.
AB  - Pancreatic duct bicarbonate secretion is mediated primarily by secretin-induced
      elevation of intracellular cyclic AMP, although little is known of the effects of
      other physiological regulators on pancreatic duct cyclic AMP metabolism. We
      investigated the effects of secretin and several other potential agonists on
      cyclic AMP levels in isolated guinea pig main and interlobular pancreatic duct
      segments and in cultured duct epithelial monolayers. Secretin (0.1 microM) caused
      a five- to eightfold elevation of cyclic AMP in both isolated ducts and cultured
      monolayers (EC50 = 0.15 nM). Main duct segments, while responsive, were less so
      than segments of interlobular duct. In isolated duct segments, carbachol,
      bombesin, cholecystokinin, substance P, calcitonin gene-related peptide,
      glucagon, insulin, isoproterenol, neurotensin, and prostaglandin E2 did not
      significantly alter resting or secretin-stimulated cyclic AMP levels. In
      contrast, 0.1 microM vasoactive intestinal peptide significantly increased cyclic
      AMP to a level comparable to that evoked by an equal concentration of secretin.
      Somatostatin significantly attenuated the effects of a submaximal (physiological)
      dose of secretin on duct cyclic AMP levels without altering resting cyclic AMP
      levels, suggesting that somatostatin's effects on pancreatic duct fluid secretion
      are mediated by inhibition of adenylyl cyclase activity.

PMID- 8577679
TI  - Protease activation in the porcine pancreatic allograft during preservation.
AB  - A porcine pancreatic transplantation model was used to investigate possible
      protease activation in the pancreatic graft during preservation. After perfusion
      with Perfadex and cold ischemia for 24 h, but prior to reperfusion, activated
      carboxypeptidase B was demonstrated in tissue samples from the graft parenchyma
      with a Western blot technique, indicating that graft pancreatitis may already be
      initiated during the preservation phase. A higher degree of carboxypeptidase B
      activation was observed in grafts perfused at a pressure of 130 cm H20 than after
      perfusion at 70 cm H20. During reperfusion, the fraction of activated
      carboxypeptidase B gradually declined but was still detectable after 2 h. One
      group of pigs received aprotinin intravenously during reperfusion, but the
      protease inhibitor did not influence the degree of carboxypeptidase B activation
      in the biopsy specimen. Immunoblotting against cationic trypsinogen/trypsin was
      also performed. When activated trypsin was detectable, it never presented more
      than a few percent of the total amount of uncomplexed immunoreactive
      trypsinogen/trypsin.

PMID- 8577681
TI  - Stimulation of endocrine, but not exocrine, pancreatic secretion during 2-deoxy-D
      glucose-induced neuroglycopenia in the conscious pig.
AB  - The effects of autonomic nervous activation, initiated by 2-deoxy-D-glucose (2
      DG)-induced neuroglycopenia, or endocrine and exocrine pancreatic secretion were
      investigated in the conscious pig. Pigs were surgically fitted with permanent
      pancreatic duct and duodenal reentrant cannulas, allowing long-term sampling of
      pancreatic juice, and a jugular vein catheter for blood sampling and infusion of
      2-DG. 2-DG was administered as a 5-min intravenous infusion at three dose levels
      to conscious pigs. 2-DG (400 mg/kg) was found to elevate plasma glucagon and
      insulin levels (p < 0.01). In contrast, exocrine pancreatic secretion, measured
      as volume, total protein output, and output of trypsin activity was not affected
      by 2-DG at the dose levels of 75, 200, and 400 mg/kg. Secretin (440 pmol/kg/h),
      however, stimulated pancreatic exocrine output of fluid (p < 0.01), protein (p <
      0.01), and trypsin (p < 0.05). It is concluded that autonomic nervous activation
      by 2-DG-induced neuroglycopenia, in the conscious pig under basal conditions,
      elevates the plasma levels of glucagon and insulin but does not affect exocrine
      pancreatic secretion. 2-DG-induced neuroglycopenia is, thus, a suitable model for
      studying autonomic neural influences on the porcine endocrine pancreas.

PMID- 8577682
TI  - Pancreatic enzyme activity after a pylorus-preserving pancreaticoduodenectomy
      reconstructed with pancreaticogastrostomy.
AB  - This study was initiated to clarify whether the main hydrolytic enzymes of the
      pancreas are activated or inactivated when secreted into the stomach of patients
      who had undergone a pylorus-preserving pancreaticoduodenectomy (PPPD) and were
      given a pancreaticogastrostomy (PG) for the reconstruction. Seventeen such
      patients, 15 cancer patients and two pancreatic patients, who underwent PPPD-PG
      reconstruction were postoperatively followed up for 3 or more years to
      investigate the influence of the gastric acid on the p-type amylase and lipase
      activity. Results revealed that when the pH was < 3.0, both the p-type amylase
      and the lipase secretion remained inactivated, but when the pH was > 3.1, the
      activity of both enzymes increased proportionately. The pancreatic enzyme
      activity in the small intestine was also investigated in seven patients, six
      cancer cases and one case of pancreatitis, given a PPPD-PG reconstruction, and it
      was found that the pancreatic enzyme activity in the small intestine increased
      after milk loading. Further, the fecal pancreatic enzyme activity was
      investigated in 17 patients given a PPPD-PG reconstruction. Results reveal that
      the fecal p-type amylase, lipase, and chymotrypsin activity amounted to 21, 27,
      and 31% of the respective values seen in 10 healthy volunteers. However, the
      fecal pancreatic enzyme activity levels did not differ significantly from the
      levels seen in 20 pancreaticoduodenectomy patients given a pancreaticojejunostomy
      reconstruction. In conclusion, it was found that the main hydrolytic enzymes of
      the pancreas are activated when the gastric acidity is over pH 3.1, which
      normally occurs after ingestion of a meal.

PMID- 8577683
TI  - An argument against routine percutaneous biopsy, ERCP, or biliary stent placement
      in patients with clinically resectable periampullary masses: a surgical
      perspective.
AB  - Improve resolution of computed tomography (CT) and ultrasonography allows us to
      visualize the proximal extent of biliary obstruction and the presence of a
      periampullary mass in most patients with malignant extrahepatic biliary
      obstruction. Our purpose in this report is to challenge the need for preoperative
      percutaneous biopsy, endoscopic retrograde cholangiopancreatography, or
      preoperative placement of a biliary endoprosthesis in the good-risk patient in
      whom the imaging procedure clearly defines a periampullary mass and the proximal
      extent (hepatic extent) of biliary obstruction. We recently managed three
      patients in whom one of these invasive procedures led to a complication that
      delayed, prevented, or complicated appropriate operative resection of a
      pancreatic neoplasm. Because a negative percutaneous biopsy, cholangiographic
      imaging of a dilated bile/pancreatic duct clearly seen on CT or ultrasonography,
      or short-term preoperative biliary decompression does not alter the decision for
      operative exploration and may cause complications, we argue against their use in
      the good-risk patient with both extrahepatic biliary obstruction and a
      periampullary pancreatic mass well delineated on noninvasive imaging.

PMID- 8577684
TI  - Pancreaticoduodenojejunostomy for chronic pancreatitis presenting with an
      inflammatory mass in the head of the pancreas.
AB  - An inflammatory mass in the head of the pancreas is reported in 18-50% of
      patients with chronic pancreatitis. When the clinical history is misleading,
      differential diagnosis between chronic pancreatitis and pancreatic cancer may be
      very difficult. Pancreaticoduodenectomy is considered the treatment of choice, if
      cancer is still suspected despite negative biopsy. From January 1987 to December
      1992 we performed 42 pancreaticoduodenectomies, 36 for malignancies of the
      pancreaticoduodenal area and 6 for chronic pancreatitis suspected to have a
      pancreatic cancer. In three additional cases of chronic pancreatitis, we
      performed a pancreaticoduodenojejunal anastomosis after complete opening of the
      pancreatic duct and excision of the papilla of Vater. Frozen section and
      definitive histological examination of the pancreas and ampulla excluded
      malignance in all three patients. They are alive and well 60, 36, and 20 months
      after operation. With this procedure, frozen-section examination of the distal
      part of the pancreatic and biliary duct, the papilla, and the periductal
      pancreatic tissue can be performed, while this is impossible with the usual
      pancreaticojejunostomy. We can therefore reasonably exclude a small cancer of the
      periampullary area and perform a wider derivative procedure, instead of a
      pancreaticoduodenectomy, in patients with an inflammatory mass of the head of the
      pancreas.

PMID- 8577685
TI  - Effect of the microtubule-disrupting drug colchicine on rat cerulein-induced
      pancreatitis in comparison with the microtubule stabilizer taxol.
AB  - Effects of colchicine, a microtubule-disrupting agent, on rate exocrine pancreas
      were examined in comparison with the microtubule stabilizer Taxol for the purpose
      of analyzing the pathogenesis of cerulein-induced acute pancreatitis. Taxol
      ameliorated the inhibition of pancreatic secretion, elevation of serum amylase
      level, pancreatic edema, and histological alterations induced by supramaximal
      cerulein stimulation. In contrast, colchicine by itself and colchicine followed
      by cerulein stimulation (maximal and supramaximal) inhibited pancreatic secretion
      but did not induce the hyperamylasemia, pancreatic edema, or formation of large
      vacuoles, which characterized cerulein-induced pancreatitis. Electron microscopic
      studies in the colchicine-treated rats revealed that transport vesicles were
      accumulated in the supranuclear region and that no large vacuoles were observed
      in the apical lesion. Immunofluorescence studies confirmed that colchicine
      inhibited pancreatic secretion and disrupted the arrangement of microtubules.
      Posttreatment of colchicine did not prevent the development of cerulein-induced
      pancreatitis. Vinblastine, another microtubule-disrupting drug, as well as
      colchicine, inhibited pancreatic secretion but did not induce acute pancreatitis.
      The results obtained in this study suggest that microtubule disorganization at a
      specific step in the process of intracellular vesicular transport causes cerulein
      induced pancreatitis and that this step is more apical than that at which
      colchicine inhibits secretion in the pancreatic acinar cell.

PMID- 8577686
TI  - Pancreatic amylin content in human diabetic subjects and its relation to
      diabetes.
AB  - To evaluate the pancreatic amylin in the pathogenesis of non-insulin-dependent
      diabetes mellitus (NIDDM), we determined the pancreatic amylin (IRA) and insulin
      (IRI) contents of pancreata obtained at autopsy from diabetics and nondiabetics.
      IRA was extracted from the tail of the pancreas using formic acid and assayed
      with a human amylin kit. Following gel filtration of amylin on a Sephadex G-50
      column, it was eluted in a similar fraction to insulin. The pancreatic IRA
      content was significantly higher (p < 0.01) in NIDDM subjects compared with
      nondiabetics, with the mean values being 4.25 +/- 1.62 and 0.085 +/- 0.022
      microgram/g, respectively. The IRA content of two IDDM pancreata was low. No
      significant relationship was found between the IRA and the IRI contents or
      between the IRA content and the duration of diabetes. However, there was a
      tendency for the IRA content to increase in longstanding diabetes. Men had a
      significantly higher pancreatic IRA content than women. The four subjects with
      very high IRA levels ( > 10 micrograms/g) were all elderly men with a long
      duration of diabetes. Thus, although the pancreatic amylin content was increased
      in NIDDM, no significant relationship to the clinical features of the disease was
      found.

PMID- 8577687
TI  - Insulin secretion and DNA synthesis of cultured islets of Langerhans are
      influenced by the matrix.
AB  - To compare the effect of matrix on glucose-stimulated insulin release, we
      cultured neonatal (3- to 5-day-old) rat islets of Langerhans, devoid of
      mesenchymal cell, on fibronectin, Cell-Tak, or endothelial basement membranes,
      free-floating, or dispersed into single cells. We also examined the rate of DNA
      synthesis during the culture period. Compared to free-floating islets [0.386 +/-
      0.03 (SEM) ng per 24 h/ng total], single-cell cultures had the lowest basal
      insulin release (0.159 +/- 0.03 ng per 24 h/ng total; p < 0.0001), which was also
      low in islets attached to endothelial basement membrane (0.294 +/- 0.02 ng per 24
      h/ng total; p = 0.01). The spontaneous insulin release (1 h in medium with 2.7 mM
      glucose) was lowest in islets attached to endothelial basement membrane (0.003 +/
      0.00023 ng per h/ng total; p < 0.0001 vs. free-floating) and highest in single
      cell cultures (0.01153 +/- 0.00259 ng per h/ng total; p = 0.039 vs. free
      floating). The ability to increase insulin release following a glucose challenge
      (16.1 mM for 1 h) was highest in islets grown on endothelial basement membranes
      (16.4-fold) and fibronectin (12.6-fold) compared to free-floating islets (8.7
      fold), Cell-Tak (7.9-fold), and single-cell cultures (5.4-fold).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8577688
TI  - Pentamidine-induced hyperglycemia and ketosis in acquired immunodeficiency
      syndrome.

PMID- 8577689
TI  - The use of zinc binding dyes and fluorescence-activated islet sorters.

PMID- 8577690
TI  - Acute pancreatitis in an octreotide-treated AIDS patient--suggested alternative
      mechanisms.

PMID- 8577691
TI  - An approach to protein homology modelling based on an ensemble of NMR structures:
      application to the Sox-5 HMG-box protein.
AB  - A new approach has been developed to reduce multiple protein structures obtained
      from NMR structure analysis to a smaller number of representative structures
      which still reflect the structural diversity of the data sets. The method, based
      on the clustering of similar structures, has been tested in the homology model
      building of the structure of Sox-5, a sequence-specific DNA-binding protein
      belonging to the high mobility group (HMG) nuclear proteins family. Sox (SRY box)
      genes are the autosomal genes related to the sex-determining SRY, Y chromosomal
      gene. The Sox-5 protein, encoded by one of the SRY-related genes, displays a 29%
      sequence identity with the HMG1 B-box domain whose structure, determined
      previously by NMR, has been used in our study to predict the structure of Sox-5.
      Two independent ensembles of HMG1 structures, each represented by closely related
      coordinate sets, were used. Nine representative structures for HMG1 were
      subsequently selected as starting points for the modelling of Sox-5. The model of
      the protein shows close similarity to the HMG1 fold, with differences at the
      secondary structure level located mainly in alpha-helices 1 and 3. A left-handed,
      three residue per turn polyproline II helix, forming a conserved polyproline
      II/alpha-helix supersecondary motif, was identified in the N-terminal region of
      Sox-5 and other HMG boxes.

PMID- 8577692
TI  - Inverse protein folding by the residue pair preference profile method: estimating
      the correctness of alignments of structurally compatible sequences.
AB  - The residue pair preference profile (R3P) method is an inverse folding method
      that combines environmental profiles and pair preference profiles. The method
      uses statistical preferences for residue pairs which score the likelihood of
      finding a profiled residue to be paired with a residue within its local
      environment. All pairs are characterized by their dihedral angles, secondary
      structure and number of neighboring residues as a function of residue type. Each
      residue pair preference is expressed for all 20 amino acids of the profiled
      residue and is weighted by the compatibility of the environment residue with its
      own local environment. The R3P method produces an initial profile-sequence
      alignment which is then refined by converting the initial profile into a profile
      of a target sequence threaded into the structure of the initial profile. We have
      tested this method by evaluating alignments of sequences with known 3-D
      structures using structural superposition alignments as reference. R3P-sequence
      alignments are > or = 50% correct on average for sequences whose 3-D structure
      pairs superimpose with an r.m.s. deviation of < or = 1.97 A. The average
      improvement in correctness during this iterative refinement is 14%. The R3P
      sequence alignments are compared with sequence-sequence and 3-D profile-sequence
      alignments. When all three methods are combined, on average > or = 50% of the
      alignments are correct for pairs of 3-D structures that superimpose within 2.12
      A. A 3-D model of HisA is predicted with the combined method.

PMID- 8577693
TI  - Context-dependent optimal substitution matrices.
AB  - Substitution matrices are a key tool in important applications such as
      identifying sequence homologies, creating sequence alignments and more recently
      using evolutionary patterns for the prediction of protein structure. We have
      derived a novel approach to the derivation of these matrices that utilizes not
      only multiple sequence alignments, but also the associated evolutionary trees.
      The key to our method is the use of a Bayesian formalism to calculate the
      probability that a given substitution matrix fits the tree structures and
      multiple sequence alignment data. Using this procedure, we can determine optimal
      substitution matrices for various local environments, depending on parameters
      such as secondary structure and surface accessibility.

PMID- 8577694
TI  - Optimal protein structure alignments by multiple linkage clustering: application
      to distantly related proteins.
AB  - A fully automatic procedure for aligning two protein structures is presented. It
      uses as sole structural similarity measure the root mean square (r.m.s.)
      deviation of superimposed backbone atoms (N, C alpha, C and O) and is designed to
      yield optimal solutions with respect to this measure. In a first step, the
      procedure identifies protein segments with similar conformations in both
      proteins. In a second step, a novel multiple linkage clustering algorithm is used
      to identify segment combinations which yield optimal global structure alignments.
      Several structure alignments can usually be obtained for a given pair of
      proteins, which are exploited here to define automatically the common structural
      core of a protein family. Furthermore, an automatic analysis of the clustering
      trees is described which enables detection of rigid-body movements between
      structure elements. To illustrate the performance of our procedure, we apply it
      to families of distantly related proteins. One groups the three alpha + beta
      proteins ubiquitin, ferredoxin and the B1-domain of protein G. Their common
      structure motif consists of four beta-strands and the only alpha-helix, with one
      strand and the helix being displaced as a rigid body relative to the remaining
      three beta-strands. The other family consists of beta-proteins from the Greek key
      group, in particular actinoxanthin, the immunoglobulin variable domain and
      plastocyanin. Their consensus motif, composed of five beta-strands and a turn, is
      identified, mostly intact, in all Greek key proteins except the trypsins, and
      interestingly also in three other beta-protein families, the lipocalins, the
      neuraminidases and the lectins. This result provides new insights into the
      evolutionary relationships in the very diverse group of all beta-proteins.

PMID- 8577695
TI  - Free energy simulations of the HyHEL-10/HEL antibody-antigen complex.
AB  - Free energy simulations are reported for the N31LD mutation, both in the HyHEL-10
      HEL antibody-lysozyme complex and in the unliganded antibody, using the
      thermodynamic-cycle perturbation method. The present study suggests that the
      mutation would change the free energy of binding of the complex by -5.6 kcal/mol
      (unrestrained free energy simulations), by -0.5 kcal/mol (free energy simulations
      with a restrained backbone) and by 1.8 kcal/mol (Poisson-Boltzmann calculations,
      which also use a restrained geometry model). A detailed structural analysis helps
      in estimating the contributions from various residues and regions of the system.
      Enhanced recognition of HEL by the mutant HyHEL-10 would arise from the
      combination of thermodynamically more favorable conformational changes of the CDR
      loops upon association and subsequent charge pairing with Lys96 in the antigen.

PMID- 8577696
TI  - Empirical free energy calculations of ligand-protein crystallographic complexes.
      I. Knowledge-based ligand-protein interaction potentials applied to the
      prediction of human immunodeficiency virus 1 protease binding affinity.
AB  - The steadily increasing number of high-resolution human immunodeficiency virus
      (HIV) 1 protease complexes has been the impetus for the elaboration of knowledge
      based mean field ligand-protein interaction potentials. These potentials have
      been linked with the hydrophobicity and conformational entropy scales developed
      originally to explain protein folding and stability. Empirical free energy
      calculations of a diverse set of HIV-1 protease crystallographic complexes have
      enabled a detailed analysis of binding thermodynamics. The thermodynamic
      consequences of conformational changes that HIV-1 protease undergoes upon binding
      to all inhibitors, and a substantial concomitant loss of conformational entropy
      by the part of HIV-1 protease that forms the ligand-protein interface, have been
      examined. The quantitative breakdown of the entropy-driven changes occurring
      during ligand-protein association, such as the hydrophobic contribution, the
      conformational entropy term and the entropy loss due to a reduction of rotational
      and translational degrees of freedom, of a system composed to ligand, protein and
      crystallographic water molecules at the ligand-protein interface has been carried
      out. The proposed approach provides reasonable estimates of distinctions in
      binding affinity and gives an insight into the nature of enthalpyentropy
      compensation factors detected in the binding process.

PMID- 8577697
TI  - Properties of N-terminal tails in G-protein coupled receptors: a statistical
      study.
AB  - The extramembraneous segments in a large collection of G-protein coupled
      receptors (GPCRs) have been analysed in terms of amino acid composition and
      length. It is shown that this family of multi-spanning integral membrane proteins
      conforms well to the 'positive inside' rule. Further, the extracellular N
      terminal tails of GPCRs lacking a cleavable signal peptide are shown to be
      considerably shorter and to have a reduced content of positively charged amnio
      acids compared with the N-terminal tails of GPCRs endowed with a signal peptide.
      This suggests that extracellular N-terminal tails of eukaryotic plasma membrane
      proteins may be translocated by different mechanisms depending on whether or not
      they are preceded by a signal peptide.

PMID- 8577698
TI  - Stereochemistry of the N-glycosylation sites in glycoproteins.
AB  - The stereochemical features displayed by the N-glycosidic linkage in crystalline
      N-linked glycoproteins are analyzed. From the statistical analysis of 44
      different glycosylation sites belonging to 26 glycoproteins of the Brookhaven
      Protein Data Bank, a mean standard geometry for the GlcNAc moiety, along with a
      rationalization of its conformational behavior, can be proposed. As for the
      glycopeptide linkage, the distribution of observed conformations has been
      analyzed on the basis of molecular mechanics calculations. The rotamer
      distribution of the Asn side chains conforms to that observed on non-glycosylated
      structures, and it agrees with the pattern of flexible conformations gathered
      from NMR measurements. In characterizing the protein-glycan interactions, some
      hydrogen bonds occur. Stacking between the amphiphilic moiety of the glycan and
      some surrounding aromatic, or at least hydrophobic, amino acid residues is also
      found. When looking at the secondary structure of the glycosylated peptide, only
      25% of the glycosylation sites correspond to situations where Asn is located at
      the top of a beta-turn. Other types of secondary structure exist which fulfill
      the spatial requirement of having the glycan exposed at the surface of the
      protein. These data can be compared with the most recent studies on the peptide
      conformation which would be required for glycosylation.

PMID- 8577699
TI  - Site-directed mutagenesis of glutathione synthetase from Escherichia coli B:
      mapping of the gamma-L-glutamyl-L-cysteine-binding site.
AB  - Lys18, Arg86, Asn283, Ser286, Thr288 and Glu292 of glutathione synthetase from
      Escherichia coli B are presumed to be highly concerned with the substrate, gamma
      L-glutamyl-L-cysteine (gamma-Glu-Cys), binding by X-ray crystallography and
      affinity labeling studies. Using site-directed mutagenesis, we investigated
      functional roles of those residues for gamma-Glu-Cys binding. The mutant enzymes
      of Arg86 and Asn283 altered their kinetic parameters, especially the Michaelis
      constants of gamma-Glu-Cys. In the case of Asn283, the residue is not likely to
      have an essential role in gamma-Glu-Cys binding but its side chain would extend
      to make a van der Waals contact with bound gamma-Glu-Cys. Chemical modification
      of a cysteine residue with 5,5'-dithiobis(2-nitrobenzoate) (DTNB) showed Arg86
      would not only be much responsible for gamma-Glu-Cys binding but would also have
      a role in maintaining the structural integrity of the enzyme. The other mutant
      enzymes showed little defect in their kinetic parameters of gamma-Glu-Cys.

PMID- 8577700
TI  - Linker modification introduces useful molecular instability in a single chain
      antibody.
AB  - SCA 4-4-20/212, is a recombinant single chain antibody directed against
      fluorescein (Fl) composed of the variable light (VL) and variable heavy (VH)
      domains of the monoclonal antibody 4-4-20, tethered by a 14 amino acid linker.
      Binding of SCA 4-4-20/212 to Fl quenches its fluorescence, thus enabling the
      distinction between bound and free Fl. This was used to follow antibody
      denaturation which followed a two-step process: rapid selected and restricted
      denaturation followed by slow and progressive denaturation. This two-phase
      phenomenon might reflect selective susceptibility of the CDR loops to
      denaturation. Furthermore, a new SCA, SCA 4-4-20/9, was constructed by site
      directed mutagenesis of SCA 4-4-20/212 using PCR methodology. SCA 4-4-20/9 was
      similar to SCA 4-4-20/212, but for a nine residue linker. The two SCAs were
      compared for Fl binding, heat stability, the effect of denaturing agents and
      susceptibility to proteolysis. The modification of the linker caused a general
      conformational rearrangement in the SCA molecule, rendering it more sensitive to
      denaturation and proteolysis. This molecular instability may find utility in the
      application of SCAs in analytical systems or as the recognition component in
      biosensors.

PMID- 8577701
TI  - Properties of a single-chain antibody containing different linker peptides.
AB  - Single-chain antibodies were constructed using six different linker peptides to
      join the VH and VL domains of an anti-2-phenyloxazolone (Ox) antibody. Four of
      the linker peptides originated from the interdomain linker region of the fungal
      cellulase CBHI and consisted of 28, 11, six and two amino acid residues. The two
      other linker peptides used were the (GGGGS)3 linker with 15 amino acid residues
      and a modified IgG2b hinge peptide with 22 residues. Proteolytic stability and Ox
      binding properties of the six different scFv derivatives produced in Escherichia
      coli were investigated and compared with those of the corresponding Fv fragment
      containing no joining peptide between the V domains. The hapten binding
      properties of different antibody fragments were studied by ELISA and BIAcoreTM.
      The interdomain linker peptide improved the hapten binding properties of the
      antibody fragment when compared with Fv fragment, but slightly increased its
      susceptibility to proteases. Single-chain antibodies with short CBHI linkers of
      11, six and two residues had a tendency to form multimers which led to a higher
      apparent affinity. The fragments with linkers longer than 11 residues remained
      monomeric.

PMID- 8577702
TI  - A highly specific and sensitive monoclonal antibody detecting histidine-tagged
      recombinant proteins.

PMID- 8577703
TI  - Catalytic activity of the mouse guanine nucleotide exchanger mSOS is activated by
      Fyn tyrosine protein kinase and the T-cell antigen receptor in T cells.
AB  - mSOS, a guanine nucleotide exchange factor, is a positive regulator of Ras. Fyn
      tyrosine protein kinase is a potential mediator in T-cell antigen receptor signal
      transduction in subsets of T cells. We investigated the functional and physical
      interaction between mSOS and Fyn in T-cell hybridoma cells. Stimulation of the T
      cell antigen receptor induced the activation of guanine nucleotide exchange
      activity in mSOS immunoprecipitates. Overexpression of Fyn mutants with an
      activated kinase mutation and with a Src homology 2 deletion mutation resulted in
      a stimulation and suppression of the mSOS activity, respectively. The complex
      formations of Fyn-Shc, Shc-Grb2, and Grb2-mSOS were detected in the activated Fyn
      transformed cells, whereas the SH2 deletion mutant of Fyn failed to form a
      complex with mSOS. Moreover, tyrosine phosphorylation of Shc was induced by the
      overexpression of the activated Fyn. These findings support the idea that Fyn
      activates the activity of mSOS bound to Grb2 through tyrosine phosphorylation of
      Shc. Unlike the current prevailing model, Fyn-induced activation of Ras might
      involve the stimulation of the catalytic guanine nucleotide exchange activity of
      mSOS.

PMID- 8577704
TI  - A new selenoprotein from human lung adenocarcinoma cells: purification,
      properties, and thioredoxin reductase activity.
AB  - We report the isolation and characterization of a new selenoprotein from a human
      lung adenocarcinoma cell line, NCI-H441. Cells were grown in RPMI-1640 medium
      containing 10% (vol/vol) fetal bovine serum and 0.1 microM [75Se]selenite. A 75Se
      labeled protein was isolated from sonic extracts of the cells by chromatography
      on DE-23, phenyl-Sepharose, heparin-agarose, and butyl-Sepharose. The protein, a
      homodimer of 57-kDa subunits, was shown to contain selenium in the form of
      selenocysteine; hydrolysis of the protein alkylated with either iodoacetate or 3
      bromopropionate yielded Se-carboxymethyl-selenocysteine or Se-carboxyethyl
      selenocysteine, respectively. The selenoprotein showed two isoelectric points at
      pH 5.2 and pH 5.3. It was distinguished from selenoprotein P by N-glycosidase
      assay and by the periodate-dansylhydrazine test, which indicated no detectable
      amounts of glycosyl groups on the protein. The selenoprotein contains FAD as a
      prosthetic group and catalyzes NADPH-dependent reduction of 5,5'-dithiobis(2
      nitrobenzoic acid) (DTNB), and reduction of insulin in the presence of
      thioredoxin (Trx). The specific activity was determined to be 31 units/mg by DTNB
      assay. Apparent Km values for DTNB, Escherichia coli Trx, and rat Trx were 116,
      34, and 3.7 microM, respectively. DTNB reduction was inhibited by 0.2 mM
      arsenite. Although the subunit composition and catalytic properties are similar
      to those of mammalian thioredoxin reductase (TR), the human lung selenoprotein
      failed to react with anti-rat liver TR polyclonal antibody in immunoblot assays.
      The selenocysteine-containing TR from the adenocarcinoma cells may be a variant
      form distinct from rat liver TR.

PMID- 8577705
TI  - Compressibility as a means to detect and characterize globular protein states.
AB  - We report compressibility data on single-domain, globular proteins which suggest
      a general relationship between protein conformational transitions and delta
      kzeroS, the change in the partial specific adiabatic compressibility which
      accompanies the transition. Specifically, we find transitions between native and
      compact intermediate states to be accompanied by small increases in kzeroS of +(1
      4) x 10(-6) cm3.g-1.bar-1 (1 bar = 100 kPa). By contrast, transitions between
      native and partially unfolded states are accompanied by small decreases in kzeroS
      of -(3-7) x 10(-6) cm3.g-1.bar-1, while native-to-fully unfolded transitions
      result in large decreases in kzeroS of -(18-20) x 10(-6) cm3.g-1.bar-1. Thus, for
      the single-domain, globular proteins studied here, changes in kzeroS correlate
      with the type of transition being monitored, independent of the specific protein.
      Consequently, kzeroS measurements may provide a convenient approach for detecting
      the existence of and for defining the nature of protein transitions, while also
      characterizing the hydration properties of individual protein states.

PMID- 8577706
TI  - Kruppel-associated box-mediated repression of RNA polymerase II promoters is
      influenced by the arrangement of basal promoter elements.
AB  - The evolutionarily conserved Kruppel-associated box (KRAB) is present in the N
      terminal regions of more than one-third of all Kruppel-class zinc finger
      proteins. Recent experiments have demonstrated that the KRAB-A domain tethered to
      a promoter DNA by connecting to heterologous DNA-binding protein domain or
      targeted to a promoter-proximal RNA sequence acts as a transcriptional silencing
      of RNA polymerase II promoters. Here we show that expression of KRAB domain
      suppresses in vivo the activating function of various defined activating
      transcription factors, and we demonstrate that the KRAB domain specifically
      silences the activity of promoters whose initiation is dependent on the presence
      of a TATA box. Promoters whose accurate transcription initiation is directed by a
      pyrimidine-rich initiator element, however, are relatively unaffected. We also
      report in vitro transcription experiments indicating that the KRAB domain is able
      to repress both activated and basal promoter activity. Thus, the KRAB domain
      appears to repress the activity of certain promoters through direct communication
      with TATA box-dependent basal transcription machinery.

PMID- 8577707
TI  - Structural changes of tumor necrosis factor alpha associated with membrane
      insertion and channel formation.
AB  - Low pH enhances tumor necrosis factor alpha (TNF)-induced cytolysis of cancer
      cells and TNF-membrane interactions that include binding, insertion, and ion
      channel formation. We have also found that TNF increases Na+ influx in cells.
      Here, we examined the structural features of the TNF-membrane interaction pathway
      that lead to channel formation. Fluorometric studies link TNF's acid-enhanced
      membrane interactions to rapid but reversible acquisition of hydrophobic surface
      properties. Intramembranous photolabeling shows that (i) protonation of TNF
      promotes membrane insertion, (ii) the physical state of the target bilayer
      affects the kinetics and efficiency of TNF insertion, and (iii) binding and
      insertion of TNF are two distinct events. Acidification relaxes the trimeric
      structure of soluble TNF so that the cryptic carboxyl termini, centrally located
      at the base of the trimer cone, become susceptible to carboxypeptidase Y. After
      membrane insertion, TNF exhibits a trimeric configuration in which the carboxyl
      termini are no longer exposed; however, the proximal salt-bridged Lys-11 residues
      as well as regional surface amino acids (Glu-23, Arg-32, and Arg-44) are notably
      more accessible to proteases. The sequenced cleavage products bear the membrane
      restricted photoreactive probe, proof that surface-cleaved TNF has an
      intramembranous disposition. In summary, the trimer's structural plasticity is a
      major determinant of its channel-forming ability. Channel formation occurs when
      cracked or partially splayed trimers bind and penetrate the bilayer. Reannealing
      leads to a slightly relaxed trimeric structure. The directionality of bilayer
      penetration conforms with x-ray data showing that receptor binding to the monomer
      interfaces of TNF poises the tip of the trimeric cone directly above the target
      cell membrane.

PMID- 8577708
TI  - Identification of a minimal sequence of the mouse pro-alpha 1(I) collagen
      promoter that confers high-level osteoblast expression in transgenic mice and
      that binds a protein selectively present in osteoblasts.
AB  - Based on our previous transgenic mice results, which strongly suggested that
      separate cell-specific cis-acting elements of the mouse pro-alpha 1(I) collagen
      promoter control the activity of the gene in different type I collagen-producing
      cells, we attempted to delineate a short segment in this promoter that could
      direct high-level expression selectively in osteoblasts. By generating transgenic
      mice harboring various fragments of the promoter, we identified a 117-bp segment
      (-1656 to -1540) that is a minimal sequence able to confer high-level expression
      of a lacZ reporter gene selectively in osteoblasts when cloned upstream of the
      proximal 220-bp pro-alpha 1(I) promoter. This 220-bp promoter by itself was
      inactive in transgenic mice and unable to direct osteoblast-specific expression.
      The 117-bp enhancer segment contained two sequences that appeared to have
      different functions. The A sequence (-1656 to -1628) was required to obtain
      expression of the lacZ gene in osteoblasts, whereas the C sequence (-1575 to 
      1540) was essential to obtain consistent and high-level expression of the lacZ
      gene in osteoblasts. Gel shift assays showed that the A sequence bound a nuclear
      protein present only in osteoblastic cells. A mutation in the A segment that
      abolished the binding of this osteoblast-specific protein also abolished lacZ
      expression in osteoblasts of transgenic mice.

PMID- 8577709
TI  - A role of Hsp60 in autoimmune diabetes: analysis in a transgenic model.
AB  - A pathogenic role for self-reactive cells against the stress protein Hsp60 has
      been proposed as one of the events leading to autoimmune destruction of
      pancreatic beta cells in the diabetes of nonobese diabetic (NOD) mice. To examine
      this hypothesis, we generated transgenic NOD mice carrying a murine Hsp60
      transgene driven by the H-2E alpha class II promoter. This would be expected to
      direct expression of the transgene to antigen-presenting cells including those in
      the thymus and so induce immunological tolerance by deletion. Detailed analysis
      of Hsp60 expression revealed that the endogenous gene is itself expressed
      strongly in thymic medullary epithelium (and weakly in cortex) yet fails to
      induce tolerance. Transgenic mice with retargeted Hsp60 showed overexpression of
      the gene in thymic cortical epithelium and in bone marrow-derived cells. Analysis
      of spontaneous T-cell responses to a panel of self and heterologous Hsp60
      antigens showed that tolerance to the protein had not been induced, although
      responses to an immunodominant 437-460 epitope implicated in disease were
      suppressed, probably indicating an epitope shift. This correlated with changes in
      disease susceptibility: insulitis in transgenic mice was substantially reduced so
      that pathology rarely progressed beyond periislet infiltration. This was
      reflected in a substantial reduction in hyperglycemia and disease. These data
      indicate that T cells specific for some epitopes of murine Hsp60 are likely to be
      involved in the islet-cell destruction that occurs in NOD mice.

PMID- 8577710
TI  - Olfactory neuroblastoma is a peripheral primitive neuroectodermal tumor related
      to Ewing sarcoma.
AB  - Olfactory neuroblastoma (ONB) is a malignant tumor of the nasal mucosa whose
      histogenesis is unclear. A relationship to neuroblastoma (NB), a pediatric tumor
      of the sympathetic nervous system, is based on morphologic similarities and the
      expression of similar neural antigens. However, the clinical presentation of ONB
      differs from that of NB, and MYCN amplification characteristic of NB is not
      observed. We have therefore examined the relationship of this malignancy to other
      classes of neural tumors. In previous studies, two ONB cell lines demonstrated
      cytogenetic features and patterns of protooncogene expression suggestive of a
      relationship to the Ewing sarcoma family of childhood peripheral primitive
      neuroectodermal tumors (pPNETs). The pPNETs show t(11;22)(q24;q12) or
      t(21;22)(q22;q12) chromosomal translocations fusing the EWS gene from 22q12 with
      either the FL11 gene on 11q24 or the ERG gene on 21q22. We therefore analyzed
      ONBs for the presence of pPNET-associated gene fusions. Both cell lines showed
      rearrangement of the EWS gene, and fluorescence in situ hybridization (FISH) of
      each case demonstrated fusion of EWS and FL11 genomic sequences. Moreover, both
      lines expressed EWS/FL11 fusion transcripts with in-frame junctions between exon
      7 of EWS and exon 6 of FL11 as described for pPNETs. We identified similar gene
      fusions in four of six primary ONB cases. None of the cases expressed tyrosine
      hydroxylase, a catecholamine biosynthetic enzyme widely expressed in NB. Our
      studies indicate that ONB is not a NB but is a member of the pPNET family.

PMID- 8577711
TI  - The chimeric genes AML1/MDS1 and AML1/EAP inhibit AML1B activation at the CSF1R
      promoter, but only AML1/MDS1 has tumor-promoter properties.
AB  - The (3;21)(q26;q22) translocation associated with treatment-related
      myelodysplastic syndrome, treatment-related acute myeloid leukemia, and blast
      crisis of chronic myeloid leukemia results in the expression of the chimeric
      genes AML1/EAP, AML1/MDS1, and AML1/EVI1. AML1 (CBFA2), which codes for the alpha
      subunit of the heterodimeric transcription factor CBF, is also involved in the
      t(8;21), and the gene coding for the beta subunit (CBFB) is involved in the
      inv(16). These are two of the most common recurring chromosomal rearrangements in
      acute myeloid leukemia. CBF corresponds to the murine Pebp2 factor, and CBF
      binding sites are found in a number of eukaryotic and viral enhancers and
      promoters. We studied the effects of AML1/EAP and AML1/MDS1 at the AML1 binding
      site of the CSF1R (macrophage-colony-stimulating factor receptor gene) promoter
      by using reporter gene assays, and we analyzed the consequences of the expression
      of both chimeric proteins in an embryonic rat fibroblast cell line (Rat1A) in
      culture and after injection into athymic nude mice. Unlike AML1, which is an
      activator of the CSF1R promoter, the chimeric proteins did not transactivate the
      CSF1R promoter site but acted as inhibitors of AML1 (CBFA2). AML1/EAP and
      AML1/MDS1 expressed in adherent Rat1A cells decreased contact inhibition of
      growth, and expression of AML1/MDS1 was associated with acquisition of the
      ability to grow in suspension culture. Expression of AML1/MDS1 increased the
      tumorigenicity of Rat1A cells injected into athymic nude mice, whereas AML1/EAP
      expression prevented tumor growth. These results suggest that expression of
      AML1/EAP and AML1/MDS1 can interfere with normal AML1 function, and that
      AML1/MDS1 has tumor-promoting properties in an embryonic rat fibroblast cell
      line.

PMID- 8577712
TI  - Sterol regulation of acetyl coenzyme A carboxylase: a mechanism for coordinate
      control of cellular lipid.
AB  - Transcription from the housekeeping promoter for the acetyl coenzyme A
      carboxylase (ACC) gene, which encodes the rate-controlling enzyme of fatty acid
      biosynthesis, is shown to be regulated by cellular sterol levels through novel
      binding sites for the sterol-sensitive sterol regulatory element binding protein
      (SREBP)-1 transcription factor. The position of the SREBP sites relative to those
      for the ubiquitous auxiliary transcription factor Sp1 is reminiscent of that
      previously described for the sterol-regulated low density lipoprotein receptor
      promoter. The experiments provide molecular evidence that the metabolism of fatty
      acids and cholesterol, two different classes of essential cellular lipids, are
      coordinately regulated by cellular lipid levels.

PMID- 8577713
TI  - Transcriptional regulation of human inducible nitric oxide synthase (NOS2) gene
      by cytokines: initial analysis of the human NOS2 promoter.
AB  - The expression of inducible nitric oxide synthase (NOS2) is complex and is
      regulated in part by gene transcription. In this investigation we studied the
      regulation of NOS2 in a human liver epithelial cell line (AKN-1) which expresses
      high levels of NOS2 mRNA and protein in response to tumor necrosis factor alpha,
      interleukin 1 beta, and interferon gamma (cytokine mix, CM). Nuclear run-on
      analysis revealed that CM transcriptionally activated the human NOS2 gene. To
      delineate the cytokine-responsive regions of the human NOS2 promoter, we
      stimulated AKN-1 cells with CM following transfection of NOS2 luciferase
      constructs. Analysis of the first 3.8 kb upstream of the NOS2 gene demonstrated
      basal promoter activity but failed to show any cytokine-inducible activity.
      However, 3- to 5-fold inductions of luciferase activity were seen in constructs
      extending up to -5.8 and -7.0 kg, and a 10-fold increase was seen upon
      transfection of a -16 kb construct. Further analysis of various NOS2 luciferase
      constructs ligated upstream of the thymidine kinase promoter identified three
      regions containing cytokine-responsive elements in the human NOS2 gene: -3.8 to 
      5.8, -5.8 to -7.0, and -7.0 to -16 kb. These results are in marked contrast with
      the murine macrophage NOS2 promoter in which only 1 kb of the proximal 5'
      flanking region is necessary to confer inducibility to lipopolysaccharide and
      interferon gamma. These data demonstrate that the human NOS2 gene is
      transcriptionally regulated by cytokines and identify multiple cytokine
      responsive regions in the 5' flanking region of the human NOS2 gene.

PMID- 8577714
TI  - Hsp90 is required for the activity of a hepatitis B virus reverse transcriptase.
AB  - The heat shock protein Hsp90 is known as an essential component of several signal
      transduction pathways and has now been identified as an essential host factor for
      hepatitis B virus replication. Hsp90 interacts with the viral reverse
      transcriptase to facilitate the formation of a ribonucleoprotein (RNP) complex
      between the polymerase and an RNA ligand. This RNP complex is required early in
      replication for viral assembly and initiation of DNA synthesis through a protein
      priming mechanism. These results thus invoke a role for the Hsp90 pathway in the
      formation of an RNP.

PMID- 8577716
TI  - Archaeal-eubacterial mergers in the origin of Eukarya: phylogenetic
      classification of life.
AB  - A symbiosis-based phylogeny leads to a consistent, useful classification system
      for all life. "Kingdoms" and "Domains" are replaced by biological names for the
      most inclusive taxa: Prokarya (bacteria) and Eukarya (symbiosis-derived nucleated
      organisms). The earliest Eukarya, anaerobic mastigotes, hypothetically originated
      from permanent whole-cell fusion between members of Archaea (e.g., Thermoplasma
      like organisms) and of Eubacteria (e.g., Spirochaeta-like organisms). Molecular
      biology, life-history, and fossil record evidence support the reunification of
      bacteria as Prokarya while subdividing Eukarya into uniquely defined subtaxa:
      Protoctista, Animalia, Fungi, and Plantae.

PMID- 8577715
TI  - Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport
      of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation
      factor 4E.
AB  - The structure of m7GpppN (where N is any nucleotide), termed cap, is present at
      the 5' end of all eukaryotic cellular mRNAs (except organellar). The eukaryotic
      initiation factor 4E (eIF-4E) binds to the cap and facilitates the formation of
      translation initiation complexes. eIF-4E is implicated in control of cell growth,
      as its overexpression causes malignant transformation of rodent cells and
      deregulates HeLa cell growth. It was suggested that overexpression of eIF-4E
      results in the enhanced translation of poorly translated mRNAs that encode growth
      promoting proteins. Indeed, enhanced expression of several proteins, including
      cyclin D1 and ornithine decarboxylase (ODC), was documented in eIF-4E
      overexpressing NTH 3T3 cells. However, the mechanism underlying this increase has
      not been elucidated. Here, we studied the mode by which eIF-4E increases the
      expression of cyclin D1 and ODC. We show that the increase in the amount of
      cyclin D1 and ODC is directly proportional to the degree of eIF-4E
      overexpression. Two mechanisms, which are not mutually exclusive, are responsible
      for the increase. In eIF-4E-overexpressing cells the rate of translation
      initiation of ODC mRNA was increased inasmuch as the mRNA sedimented with heavier
      polysomes. For cyclin D1 mRNA, translation initiation was not increased, but
      rather its amount in the cytoplasm increased, without a significant increase in
      total mRNA. Whereas, in the parental NIH 3T3 cell line, a large proportion of the
      cyclin D1 mRNA was confined to the nucleus, in eIF-4E-overexpressing cells the
      vast majority of the mRNA was present in the cytoplasm. These results indicate
      that eIF-4E affects directly or indirectly mRNA nucleocytoplasmic transport, in
      addition to its role in translation initiation.

PMID- 8577717
TI  - DANA elements: a family of composite, tRNA-derived short interspersed DNA
      elements associated with mutational activities in zebrafish (Danio rerio).
AB  - DNA is the first SINE isolated from zebrafish (Danio rerio) exhibiting all the
      hallmarks of these tRNA-derived elements. DANA is unique in its clearly defined
      substructure of distinct cassettes. In contrast to generic SINE elements, DANA
      appears to have been assembled by insertions of short sequences into a
      progenitor, tRNA-derived element. Once associated with each other, these subunits
      were amplified as a new transposable element with such a remarkable success that
      DANA-related sequences comprise approximately 10% of the modern zebrafish genome.
      At least some of the sequences comprised by the full-length element were capable
      of movement, forming a new group of mobile, composite transposons, one of which
      caused an insertional mutation in the zebrafish no tail gene. Being present only
      in the genus Danio, and estimated to be as old as the genus itself, DANA may have
      played a role in Danio speciation by massive amplification and genome-wide
      dispersion. There are extensive DNA polymorphisms between zebrafish populations
      and strains detected by PCR amplification using primers specific to DANA,
      suggesting that the DANA element will be useful as a molecular tool for genetic
      and phylogenetic analyses.

PMID- 8577718
TI  - Fine mapping of colon tumor susceptibility (Scc) genes in the mouse, different
      from the genes known to be somatically mutated in colon cancer.
AB  - The predisposition to colon cancer is multigenetically controlled in animals and
      probably also in humans. We have analyzed the multigenic control of
      susceptibility to 1,2-dimethylhydrazine-induced colon tumors in mice by using a
      set of 20 homozygous CcS/Dem recombinant congenic strains, each of which contains
      a different random subset of approximately 12.5% of genes from the susceptible
      strain STS/A and 87.5% of genes from the relatively resistant strain BALB/cHeA.
      Some CcS/Dem strains received the alleles from the susceptible strain STS/A at
      one or more of the multiple colon tumor susceptibility loci and are susceptible,
      whereas others are resistant. Linkage analysis shows that these susceptibility
      genes are different from the mouse homologs of the genes known to be somatically
      mutated in human colon cancer (KRAS2, TP53, DCC, MCC, APC, MSH2, and probably
      also MLH1). Different subsets of genes control tumor numbers and size. Two colon
      cancer susceptibility genes, Scc1 and Scc2, map to mouse chromosome 2. The Scc1
      locus has been mapped to a narrow region of 2.4 centimorgans (90% confidence
      interval).

PMID- 8577719
TI  - DNA damage enhances melanogenesis.
AB  - Although the ability of UV irradiation to induce pigmentation in vivo and in
      vitro is well documented, the intracellular signals that trigger this response
      are poorly understood. We have recently shown that increasing DNA repair after
      irradiation enhances UV-induced melanization. Moreover, addition of small DNA
      fragments, particularly thymine dinucleotides (pTpT), selected to mimic sequences
      excised during the repair of UV-induced DNA photoproducts, to unirradiated
      pigment cells in vitro or to guinea pig skin in vivo induces a pigment response
      indistinguishable from UV-induced tanning. Here we present further evidence that
      DNA damage and/or the repair of this damage increases melanization. (i) Treatment
      with the restriction enzyme Pvu II or the DNA-damaging chemical agents methyl
      methanesulfonate (MMS) or 4-nitroquinoline 1-oxide (4-NQO) produces a 4- to 10
      fold increase in melanin content in Cloudman S91 murine melanoma cells and an up
      to 70% increase in normal human melanocytes, (ii) UV irradiation, MMS, and pTpT
      all upregulate the mRNA level for tyrosinase, the rate-limiting enzyme in melanin
      biosynthesis. (iii) Treatment with pTpT or MMS increases the response of S91
      cells to melanocyte-stimulating hormone (MSH) and increases the binding of MSH to
      its cell surface receptor, as has been reported for UV irradiation. Together,
      these data suggest that UV-induced DNA damage and/or the repair of this damage is
      an important signal in the pigmentation response to UV irradiation. Because Pvu
      II acts exclusively on DNA and because MMS and 4-NQO, at the concentrations used,
      primarily interact with DNA, such a stimulus alone appears sufficient to induce
      melanogenesis. Of possible practical importance, the dinucleotide pTpT mimics
      most, if not all, of the effects of UV irradiation on pigmentation, tyrosinase
      mRNA regulation, and response to MSH without the requirement for antecedent DNA
      damage.

PMID- 8577720
TI  - Mutation detection by highly sensitive methods indicates that p53 gene mutations
      in breast cancer can have important prognostic value.
AB  - Human cancer cells with a mutated p53 tumor-suppressor gene have a selective
      growth advantage and may exhibit resistance to ionizing radiation and certain
      chemotherapeutic agents. To examine the prognostic value of mutations in the p53
      gene, a cohort of 90 Midwestern Caucasian breast cancer patients were analyzed
      with methodology that detects virtually 100% of all mutations. The presence of a
      p53 gene mutation was by far the single most predictive indicator for recurrence
      and death (relative risks of 4.7 and 23.2, respectively). Direct detection of p53
      mutations had substantially greater prognostic value than immunohistochemical
      detection of p53 overexpression. Analysis of p53 gene mutations may permit
      identification of a subset of breast cancer patients who, despite lack of
      conventional indicators of poor prognosis, are at high risk of early recurrence
      and death.

PMID- 8577721
TI  - An auxiliary factor containing a 240-kDa protein complex is involved in
      apolipoprotein B RNA editing.
AB  - A protein complex involved in apolipoprotein B (apoB) RNA editing, referred to as
      AUX240 (auxiliary factor containing p240), has been identified through the
      production of monoclonal antibodies against in vitro assembled 27S editosomes.
      The 240-kDa protein antigen of AUX240 colocalized with editosome complexes on
      immunoblots of native gels. Immunoadsorbed extracts were impaired in their
      ability to assemble editosomes beyond early intermediates and in their ability to
      edit apoB RNA efficiently. Supplementation of adsorbed extract with AUX240
      restored both editosome assembly and editing activities. Several proteins, in
      addition to p240, ranging in molecular mass from 150 to 45 kDa coimmunopurify as
      AUX240 under stringent wash conditions. The activity of the catalytic subunit of
      the editosome APOBEC-1 and mooring sequence RNA binding proteins of 66 and 44 kDa
      could not be demonstrated in AUX240. The data suggest that p240 and associated
      proteins constitute an auxiliary factor required for efficient apoB RNA editing.
      We propose that the role of AUX240 may be regulatory and involve mediation or
      stabilization of interactions between APOBEC-1 subunits and editing site
      recognition proteins leading the assembly of the rat liver C/U editosome.

PMID- 8577722
TI  - Clustered syk tyrosine kinase domains trigger phagocytosis.
AB  - Phagocytosis is a phylogenetically primitive mechanism adapted by specialized
      cells of the immune system to ingest particulate pathogens. Recent evidence
      suggests that the program of specific cytoskeletal rearrangements that underlies
      phagocytosis may share elements with the antigen receptor signaling pathway in
      lymphocytes. Tyrosine phosphorylation, necessary for both lymphocyte effector
      function and phagocytosis, is thought to allow cytoskeletal elements to couple to
      the intracellular domains of antigen and Fc receptor subunits. We show here that
      the intracellular domains of the receptors are not inherently required for
      cytoskeletal coupling. Chimeric transmembrane proteins bearing syk but not src
      family tyrosine kinase domains are capable of autonomously triggering
      phagocytosis and redistribution of filamentous actin in COS cells. These
      responses cannot be initiated by a receptor chimera bearing a point mutation in
      the syk catalytic domain, and the kinase domain alone is sufficient for
      initiating cytoskeletal coupling.

PMID- 8577723
TI  - Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors.
AB  - Sensitization of primary afferent neurons underlies much of the pain and
      tenderness associated with tissue injury and inflammation. The increase in
      excitability is caused by chemical agents released at the site of injury. Because
      recent studies suggest that an increase in voltage-gated Na+ currents may
      underlie increases in neuronal excitability associated with injury, we have
      tested the hypothesis that a tetrodotoxin-resistant voltage-gated Na+ current
      (TTX-R INa), selectively expressed in a subpopulation of sensory neurons with
      properties of nociceptors, is a target for hyperalgesic agents. Our results
      indicate that three agents that produce tenderness or hyperalgesia in vivo,
      prostaglandin E2, adenosine, and serotonin, modulate TTX-R INa. These agents
      increase the magnitude of the current, shift its conductance-voltage relationship
      in a hyperpolarized direction, and increase its rate of activation and
      inactivation. In contrast, thromboxane B2, a cyclooxygenase product that does not
      produce hyperalgesia, did not affect TTX-R INa. These results suggest that
      modulation of TTX-R INa is a mechanism for sensitization of mammalian
      nociceptors.

PMID- 8577724
TI  - Stimulation of growth factor receptor signal transduction by activation of
      voltage-sensitive calcium channels.
AB  - To understand the mechanisms by which electrical activity may generate long-term
      responses in the nervous system, we examined how activation of voltage-sensitive
      calcium channels (VSCCs) can stimulate the Ras/mitogen-activated protein kinase
      (MAPK) signaling pathway. Calcium influx through L-type VSCCs leads to tyrosine
      phosphorylation of the adaptor protein Shc and its association with the adaptor
      protein Grb2, which is bound to the guanine nucleotide exchange factor Sos1. In
      response to calcium influx, Shc, Grb2, and Sos1 inducibly associate with a 180
      kDa tyrosine-phosphorylated protein, which was determined to be the epidermal
      growth factor receptor (EGFR). Calcium influx induces tyrosine phosphorylation of
      the EGFR to levels that can activate the MAPK signaling pathway. Thus, ion
      channel activation stimulates growth factor receptor signal transduction.

PMID- 8577725
TI  - Protein-protein interactions in eukaryotic transcription initiation: structure of
      the preinitiation complex.
AB  - We have used alanine scanning to analyze protein-protein interactions by human
      TATA-element binding protein (TBP) within the transcription preinitiation
      complex. The results indicate that TBP interacts with RNA polymerase II and
      general transcription factors IIA, IIB, and IIF within the functional
      transcription preinitiation complex and define the determinants of TBP for each
      of these interactions. The results permit construction of a model for the
      structure of the preinitiation complex.

PMID- 8577726
TI  - On the nucleation and growth of amyloid beta-protein fibrils: detection of nuclei
      and quantitation of rate constants.
AB  - We have studied the fibrillogenesis of synthetic amyloid beta-protein-(1-40)
      fragment (A beta) in 0.1 M HCl. At low pH, A beta formed fibrils at a rate
      amenable to detailed monitoring by quasi-elastic light-scattering spectroscopy.
      Examination of the fibrils with circular dichroism spectroscopy and electron
      microscopy showed them to be highly similar to those found in amyloid plaques. We
      determined the hydrodynamic radii of A beta aggregates during the entire process
      of fibril nucleation and growth. Above an A beta concentration of approximately
      0.1 mM, the initial rate of elongation and the final size of fibrils were
      independent of A beta concentration. Below an A beta concentration of 0.1 mM, the
      initial elongation rate was proportional to the peptide concentration, and the
      resulting fibrils were significantly longer than those formed at higher
      concentration. We also found that the surfactant n-dodecylhexaoxyethylene glycol
      monoether (C12E6) slowed nucleation and elongation of fibrils in a concentration
      dependent manner. Our observations are consistent with a model of A beta
      fibrillogenesis that includes the following key steps: (i) peptide micelles form
      above a certain critical A beta concentration, (ii) fibrils nucleate within these
      micelles or on heterogeneous nuclei (seeds), and (iii) fibrils grow by
      irreversible binding of monomers to fibril ends. Interpretation of our data
      enabled us to determine the sizes of fibril nuclei and A beta micelles and the
      rates of fibril nucleation (from micelles) and fibril elongation. Our approach
      provides a powerful means for the quantitative assay of A beta fibrillogenesis.

PMID- 8577727
TI  - Transformation of Plasmodium falciparum malaria parasites by homologous
      integration of plasmids that confer resistance to pyrimethamine.
AB  - Plasmodium falciparum malaria parasites were transformed with plasmids containing
      P. falciparum or Toxoplasma gondii dihydrofolate reductase-thymidylate synthase
      (dhfr-ts) coding sequences that confer resistance to pyrimethamine. Under
      pyrimethamine pressure, transformed parasites were obtained that maintained the
      transfected plasmids as unrearranged episomes for several weeks. These parasite
      populations were replaced after 2 to 3 months by parasites that had incorporated
      the transfected DNA into nuclear chromosomes. Depending upon the particular
      construct used for transformation, homologous integration was detected in the P.
      falciparum dhfr-ts locus (chromosome 4) or in hrp3 and hrp2 sequences that were
      used in the plasmid constructs as gene control regions (chromosomes 13 and 8,
      respectively). Transformation by homologous integration sets the stage for
      targeted gene alterations and knock-outs that will advance understanding of P.
      falciparum.

PMID- 8577728
TI  - Role of hydrophobic interactions and desolvation in determining the structural
      properties of a model alpha beta peptide.
AB  - Model AB, a 20-amino acid peptide that was designed to adopt an alpha beta
      tertiary structure stabilized by hydrophobic interactions between residues in
      adjacent helical and extended segments, exhibited large pKa shifts of several
      ionizable groups and slow hydrogen/deuterium exchange rates of nearly all the
      peptide amide groups [Butcher, D. J., Bruch, M. D. & Moe, G. T. (1995)
      Biopolymers 36, 109-120]. These properties, which depend on structure and
      hydration, are commonly observed in larger proteins but are quite unusual for
      small peptides. To identify which of several possible features of the peptide
      design are most important in determining these properties, several closely
      related analogs of Model AB were characterized by CD and NMR spectroscopy. The
      results show that hydrophobic interactions between adjacent helical and extended
      segments are structure-determining and have the additional effect of altering
      water-peptide interactions over much of the peptide surface. These results may
      have important implications for understanding mechanisms of protein folding and
      for the design of independently folding peptides.

PMID- 8577729
TI  - Differential functions of the two Src homology 2 domains in protein tyrosine
      phosphatase SH-PTP1.
AB  - SH-PTP1 (also known as PTP1C, HCP, and SHP) is a non-transmembrane protein
      tyrosine phosphatase (PTPase) containing two tandem Src homology 2 (SH2) domains.
      We show here that the two SH2 (N-SH2 and C-SH2) domains in SH-PTP1 have different
      functions in regulation of the PTPase domain and thereby signal transduction.
      While the N-terminal SH2 domain is both necessary and sufficient for
      autoinhibition through an intramolecular association with the PTPase domain,
      truncation of the C-SH2 domain [SH-PTP1 (delta CSH2) construct] has little effect
      on SH-PTP1 activity. A synthetic phosphotyrosine residue (pY) peptide derived
      from the erythropoietin receptor (EpoR pY429) binds to the N-SH2 domain and
      activates both wild-type SH-PTP1 and SH-PTP1 (delta CSH2) 60- to 80-fold. Another
      pY peptide corresponding to a phosphorylation site on the IgG Fc receptor (Fc
      gamma RIIB1 pY309) associates with both the C-SH2 domain (Kd = 2.8 microM and the
      N-SH2 domain (Kd = 15.0 microM) and also activates SH-PTP1 12-fold. By analysis
      of the effect of the Fc gamma RIIB1 pY309 peptide on SH-PTP1 (delta CSH2), SH
      PTP1 (R30K/R33E), SH-PTP1 (R30K/R136K), and SH-PTP1 (R136K) mutants in which the
      function of either the N- or C-SH2 domain has been impaired, we have determined
      that both synthetic pY peptides stimulate SH-PTP1 by binding to its N-SH2 domain;
      binding of pY ligand to the C-SH2 domain has no effect on SH-PTP1 activity. We
      propose that the N-terminal SH2 domain serves both as a regulatory domain and as
      a recruiting unit, whereas the C-terminal SH2 domain acts merely as a recruiting
      unit.

PMID- 8577730
TI  - The wing of the enhancer-binding domain of Mu phage transposase is flexible and
      is essential for efficient transposition.
AB  - A tetramer of the Mu transposase (MuA) pairs the recombination sites, cleaves the
      donor DNA, and joins these ends to a target DNA by strand transfer. Juxtaposition
      of the recombination sites is accomplished by the assembly of a stable synaptic
      complex of MuA protein and Mu DNA. This initial critical step is facilitated by
      the transient binding of the N-terminal domain of MuA to an enhancer DNA element
      within the Mu genome (called the internal activation sequence, IAS). Recently we
      solved the three-dimensional solution structure of the enhancer-binding domain of
      Mu phage transposase (residues 1-76, MuA76) and proposed a model for its
      interaction with the IAS element. Site-directed mutagenesis coupled with an in
      vitro transposition assay has been used to assess the validity of the model. We
      have identified five residues on the surface of MuA that are crucial for stable
      synaptic complex formation but dispensable for subsequent events in
      transposition. These mutations are located in the loop (wing) structure and
      recognition helix of the MuA76 domain of the transposase and do not seriously
      perturb the structure of the domain. Furthermore, in order to understand the
      dynamic behavior of the MuA76 domain prior to stable synaptic complex formation,
      we have measured heteronuclear 15N relaxation rates for the unbound MuA76 domain.
      In the DNA free state the backbone atoms of the helix-turn-helix motif are
      generally immobilized whereas the residues in the wing are highly flexible on the
      pico- to nanosecond time scale. Together these studies define the surface of MuA
      required for enhancement of transposition in vitro and suggest that a flexible
      loop in the MuA protein required for DNA recognition may become structurally
      ordered only upon DNA binding.

PMID- 8577731
TI  - Origin and evolution of circular waves and spirals in Dictyostelium discoideum
      territories.
AB  - Randomly distributed Dictyostelium discoideum cells form cooperative territories
      by signaling to each other with cAMP. Cells initiate the process by sending out
      pulsatile signals, which propagate as waves. With time, circular and spiral
      patterns form. We show that by adding spatial and temporal noise to the levels of
      an important regulator of external cAMP levels, the cAMP phosphodiesterase
      inhibitor, we can explain the natural progression of the system from randomly
      firing cells to circular waves whose symmetries break to form double- and single-
      or multi-armed spirals. When phosphodiesterase inhibitor is increased with time,
      mimicking experimental data, the wavelength of the spirals shortens, and a
      proportion of them evolve into pairs of connected spirals. We compare these
      results to recent experiments, finding that the temporal and spatial
      correspondence between experiment and model is very close.

PMID- 8577732
TI  - Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain.
AB  - A long-term goal in the field of restriction-modification enzymes has been to
      generate restriction endonucleases with novel sequence specificities by mutating
      or engineering existing enzymes. This will avoid the increasingly arduous task of
      extensive screening of bacteria and other microorganisms for new enzymes. Here,
      we report the deliberate creation of novel site-specific endonucleases by linking
      two different zinc finger proteins to the cleavage domain of Fok I endonuclease.
      Both fusion proteins are active and under optimal conditions cleave DNA in a
      sequence-specific manner. Thus, the modular structure of Fok I endonuclease and
      the zinc finger motifs makes it possible to create "artificial" nucleases that
      will cut DNA near a predetermined site. This opens the way to generate many new
      enzymes with tailor-made sequence specificities desirable for various
      applications.

PMID- 8577733
TI  - Genetic engineering of carbohydrate biosynthetic pathways in transgenic mice
      demonstrates cell cycle-associated regulation of glycoconjugate production in
      small intestinal epithelial cells.
AB  - Proliferation, migration-associated differentiation, and cell death occur
      continuously and in a spatially well-organized fashion along the crypt-villus
      axis of the mouse small intestine, making it an attractive system for studying
      how these processes are regulated and interrelated. A pathway for producing
      glycoconjugates was engineered in adult FVB/N transgenic mice by expressing a
      human alpha 1,3/4-fucosyltransferase (alpha 1,3/4-FT; EC 2.4.1.65) along the
      length of this crypt-villus axis. The alpha 1,3/4-FT can use lacto-N-tetraose or
      lacto-neo-N-tetraose core chains to generate Lewis (Le) blood group antigens
      Le(a) or Le(x), respectively, and H type 1 or H type 2 core chains to produce Leb
      and Le(y). Single- and multilabel immunohistochemical studies revealed that
      expression of the alpha 1,3/4-FT results in production of Le(a) and Leb antigens
      in both undifferentiated proliferated crypt cells and in differentiated
      postmitotic villus-associated epithelial cells. In contrast, Le(x) antigens were
      restricted to crypt cells. Villus enterocytes can be induced to reenter the cell
      cycle by expression of simian virus 40 tumor antigen under the control of a
      promoter that only functions in differentiated members of this lineage.
      Bitransgenic animals, generated from a cross of FVB/N alpha 1,3/4-FT with FVB/N
      simian virus 40 tumor antigen mice, expand the range of Le(x) expression to
      include villus-associated enterocytes that have reentered the cell cycle. Thus,
      the fucosylations unveil a proliferation-dependent switch in oligosaccharide
      production, as defined by a monoclonal antibody specific for the Le(x) epitope.
      These findings show that genetic engineering of oligosaccharide biosynthetic
      pathways can be used to define markers for entry into, or progression through,
      the cell cycle and to identify changes in endogenous carbohydrate metabolism that
      occur when proliferative status is altered in a manner that is not deleterious to
      the system under study.

PMID- 8577734
TI  - Uptake of fluorescent dyes associated with the functional expression of the
      cystic fibrosis transmembrane conductance regulator in epithelial cells.
AB  - Specific mutations in the cystic fibrosis transmembrane conductance regulator
      (CFTR), the most common autosomal recessive fatal genetic disease of Caucasians,
      result in the loss of epithelial cell adenosine 3',5'-cyclic-monophosphate (cAMP)
      stimulated Cl- conductance. We show that the influx of a fluorescent dye,
      dihydrorhodamine 6G (dR6G), is increased in cells expressing human CFTR after
      retrovirus- and adenovirus-mediated gene transfer. dR6G influx is stimulated by
      cAMP and is inhibited by antagonists of cAMP action. Dye uptake is ATP-dependent
      and inhibited by Cl- removal or the addition of 10 mM SCN-. Increased staining is
      associated with functional activation of CFTR Cl- permeability. dR6G staining
      enables both the fluorescent assessment of CFTR function and the identification
      of successfully corrected cells after gene therapy.

PMID- 8577735
TI  - Transcriptional activation by protein-induced DNA bending: evidence for a DNA
      structural transmission model.
AB  - Integration host factor (IHF) is a DNA-bending protein that binds to an upstream
      activating sequence (UAS1) and, on a negatively supercoiled DNA template,
      activates transcription from the ilvPG promoter of the ilvG-MEDA operon of
      Escherichia coli. The transcriptional initiation site of the ilvGMEDA operon is
      located 92 bp downstream of UAS1. Activation is still observed when the
      orientation of the upstream IHF binding site is reversed. This manipulation
      places the IHF binding site on the opposite face of the DNA helix, directs the
      IHF-induced DNA bend in the opposite direction, and presents the opposite face of
      the nonsymmetrical, heterodimeric, IHF molecule to the downstream RNA polymerase.
      Lymphoid enhancer-binding factor, LEF-1, is a DNA-bending, lymphoid-specific,
      mammalian transcription factor that shares no amino acid sequence similarity with
      IHF. When the IHF site in UAS1 is replaced with a LEF-1 site, LEF-1 activates
      transcription from the downstream ilvPG promoter in E. coli as well as it is
      activated by its natural activator, IHF. These results suggest that specific
      interactions between IHF and RNA polymerase are not required for activation. The
      results of DNA structural studies show that IHF forms a protein-DNA complex in
      the UAS1 region that, in the absence of RNA polymerase, alters the structure of
      the DNA helix in the -10 hexanucleotide region of the downstream ilvPG promoter.
      The results of in vitro abortive transcription assays show that IIIF also
      increases the apparent rate of RNA polymerase isomerization from a closed to an
      open complex. We suggest, therefore, that IHF activates transcription by forming
      a higher-order protein-DNA complex in the UAS1 region that structurally alters
      the DNA helix in a way that facilitates open complex formation at the downstream
      ilvPG promoter site.

PMID- 8577736
TI  - Myristate exchange on the Trypanosoma brucei variant surface glycoprotein.
AB  - The glycosyl-phosphatidylinositol (GPI) anchor of the Trypanosoma brucei variant
      surface glycoprotein (VSG) is unique in having exclusively myristate as its fatty
      acid component. We previously demonstrated that the myristate specificity is the
      result of two independent pathways. First, the newly synthesized free GPI, which
      is not myristoylated, undergoes fatty acid remodeling to replace both its fatty
      acids with myristate. Second, the myristoylated precursor, glycolipid A,
      undergoes a myristate exchange reaction, detected by the replacement of unlabeled
      myristate by [3H]myristate. Remodeling and exchange have different enzymatic
      properties and apparently occur in different subcellular compartments. We now
      demonstrate that the GPI anchor linked to VSG is the major substrate for
      myristate exchange. VSG can be efficiently labeled with [3H]myristate by exchange
      in the presence of cycloheximide, an inhibitor that prevents new VSG synthesis
      and thus anchor addition to protein. Not only is newly synthesized VSG subject to
      exchange, but mature VSG, possibly recycling from the cell surface, also
      undergoes myristate exchange.

PMID- 8577737
TI  - Multiplex selection technique (MuST): an approach to clone transcription factor
      binding sites.
AB  - We have used a multiplex selection approach to construct a library of DNA-protein
      interaction sites recognized by many of the DNA-binding proteins present in a
      cell type. An estimated minimum of two-thirds of the binding sites present in a
      library prepared from activated Jurkat T cells represent authentic transcription
      factor binding sites. We used the library for isolation of "optimal" binding site
      probes that facilitated cloning of a factor and to identify binding activities
      induced within 2 hr of activation of Jurkat cells. Since a large fraction of the
      oligonucleotides obtained appear to represent "optimal" binding sites for
      sequence-specific DNA-binding proteins, it is feasible to construct a catalog of
      consensus binding sites for DNA-binding proteins in a given cell type.
      Qualitative and quantitative comparisons of the catalogs of binding site
      sequences from various cell types could provide valuable insights into the
      process of differentiation acting at the level of transcriptional control.

PMID- 8577738
TI  - Phylogenetic resolution within the Elephantidae using fossil DNA sequence from
      the American mastodon (Mammut americanum) as an outgroup.
AB  - DNA was extracted from the extinct American mastodon, the extinct woolly mammoth,
      and the modern Asian and African elephants to test the traditional
      morphologically based phylogeny within Elephantidae. Phylogenetic analyses of the
      aligned sequences of the mitochondrial gene cytochrome b support a monophyletic
      Asian elephant-woolly mammoth clade when the American mastodon is used as an
      outgroup. Previous molecular studies were unable to resolve the relationships of
      the woolly mammoth, Asian elephant, and African elephant because the sequences
      appear to have evolved at heterogeneous rates and inappropriate outgroups were
      used for analysis. The results demonstrate the usefulness of fossil molecular
      data from appropriate sister taxa for resolving phylogenies of highly derived or
      early radiating lineages.

PMID- 8577739
TI  - HLH106, a Drosophila transcription factor with similarity to the vertebrate
      sterol responsive element binding protein.
AB  - We cloned a Drosophila homolog to the sterol responsive element binding proteins
      (SREBPs). In vertebrates, the SREBPs are regulated by a mechanism that involves
      cleavage of the protein that normally residues in the cellular membranes and
      translocation of the released transcription factor into the nucleus. Regulation
      of the Drosophila factor HLH106 apparently follows the same mechanism, and we
      find the full-length gene product in the membrane fraction and a shorter cross
      reacting form in the nuclear fraction. This nuclear form, which may correspond to
      proteolytically activated HLH106, is abundant in the blood cell line mbn-2. The
      general domain structure of HLH106 is very similar to that in SREBP. HLH106 is
      expressed throughout development, and it is present at high levels in Drosophila
      cell lines. In contrast to the rat homolog, HLH106 transcripts are not more
      abundant in adipose tissue than in other tissues.

PMID- 8577740
TI  - Regulation of N-methyl-D-aspartate-induced toxicity in the neostriatum: a role
      for metabotropic glutamate receptors?
AB  - Glutamate release activates multiple receptors that interact with each other and
      thus determine the response of the cell. Exploring these interactions is critical
      to developing an understanding of the functional consequences of synaptic
      transmission. Activation of metabotropic glutamate receptors (mGluRs) inhibits N
      methyl-D-aspartate (NMDA)-evoked responses measured electrophysiologically in
      neostriatal slices. The present study examines the functional consequences of
      this regulation using infrared differential interference contrast videomicroscopy
      to measure and characterize glutamate receptor-induced cell swelling in a
      neostriatal brain slice preparation. This swelling is, in many cases, a prelude
      to necrotic cell death and the dye trypan blue was used to confirm that swelling
      can result in the death of neostriatal cells. Activation of mGluRs by the agonist
      1-aminocyclopentane-1,3-dicarboxylic acid (tACPD) inhibited NMDA but not amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid/kainate-induced swelling. This
      regulation was cell-type specific as tACPD did not alter NMDA-induced swelling in
      pyramidal cells of the hippocampus. Importantly, these findings could be extended
      to in vivo preparations. Pretreatment with tACPD limited the size of lesions and
      associated behavioral deficits induced by intrastriatal administration of the
      NMDA receptor agonist quinolinic acid.

PMID- 8577741
TI  - Dominant-negative mutant thyroid hormone receptors prevent transcription from
      Xenopus thyroid hormone receptor beta gene promoter in response to thyroid
      hormone in Xenopus tadpoles in vivo.
AB  - We describe a dominant-negative approach in vivo to assess the strong, early
      upregulation of thyroid hormone receptor beta (TR beta) gene in response to
      thyroid hormone, characteristic of the onset of natural and thyroid hormone
      induced amphibian metamorphosis, 3,3',5-Triiodo-thyronine (T3) treatment of organ
      cultures of premetamorphic Xenopus tadpole tails coinjected in vivo with the wild
      type Xenopus TR beta (wt-xTR beta) and three different thyroid responsive element
      chloramphenicol acetyltransferase (TRE-CAT) reporter constructs, including a
      direct repeat +4 (DR +4) element in the -200/+87 fragment of the xTR beta
      promoter, resulted in a 4- to 8-fold enhancement of CAT activity. Two human C
      terminal TR beta 1 mutants (delta-hTR beta 1 and Ts-hTR beta 1), an artificial
      Xenopus C-terminal deletion mutant (mt-xTR beta), and the oncogenic viral
      homology v-erbA, none of which binds T3, inhibited this T3 response of the
      endogenous wt-xTR in Xenopus XTC-2 cells cotransfected with the -1600/+87 xTR
      beta promoter-CAT construct, the potency of the dominant-negative effect of these
      mutant TRs being a function of the strength of their heterodimerization with
      Xenopus retinoid X receptor gamma. Coinjection of the dominant-negative Xenopus
      and human mutant TR beta s into Xenopus tadpole tails totally abolished the T3
      responsiveness of the wt-xTR beta with different TREs, including the natural DR
      +4 TRE of the xTR beta promoter.

PMID- 8577742
TI  - A cell cycle-regulated bacterial DNA methyltransferase is essential for
      viability.
AB  - The CcrM adenine DNA methyltransferase, which specifically modifies GANTC
      sequences, is necessary for viability in Caulobacter crescentus. To our
      knowledge, this is the first example of an essential prokaryotic DNA
      methyltransferase that is not part of a DNA restriction/modification system.
      Homologs of CcrM are widespread in the alpha subdivision of the Proteobacteria,
      suggesting that methylation at GANTC sites may have important functions in other
      members of this diverse group as well. Temporal control of DNA methylation state
      has an important role in Caulobacter development, and we show that this organism
      utilizes an unusual mechanism for control of remethylation of newly replicated
      DNA. CcrM is synthesized de novo late in the cell cycle, coincident with full
      methylation of the chromosome, and is then subjected to proteolysis prior to cell
      division.

PMID- 8577743
TI  - 31P magnetic resonance spectroscopy of the Sherpa heart: a
      phosphocreatine/adenosine triphosphate signature of metabolic defense against
      hypobaric hypoxia.
AB  - Of all humans thus far studied, Sherpas are considered by many high-altitude
      biomedical scientists as most exquisitely adapted for life under continuous
      hypobaric hypoxia. However, little is known about how the heart is protected in
      hypoxia. Hypoxia defense mechanisms in the Sherpa heart were explored by in vivo,
      noninvasive 31P magnetic resonance spectroscopy. Six Sherpas were examined under
      two experimental conditions [normoxic (21% FiO2) and hypoxic (11% FiO2) and in
      two adaptational states--the acclimated state (on arrival at low-altitude study
      sites) and the deacclimating state (4 weeks of ongoing exposure to low altitude).
      Four lowland subjects were used for comparison. We found that the concentration
      ratios of phosphocreatine (PCr)/adenosine triphosphate (ATP) were maintained at
      steady-state normoxic values (0.96, SEM = 0.22) that were about half those found
      in normoxic lowlanders (1.76, SEM = 0.03) monitored the same way at the same
      time. These differences in heart energetic status between Sherpas and lowlanders
      compared under normoxic conditions remained highly significant (P < 0.02) even
      after 4 weeks of deacclimation at low altitudes. In Sherpas under acute hypoxia,
      the heart rate increased by 20 beats per min from resting values of about 70
      beats per min, and the percent saturation of hemoglobin decreased to about 75%.
      However, these perturbations did not alter the PCr/ATP concentration ratios,
      which remained at about 50% of the values expected in healthy lowlanders. Because
      the creatine phosphokinase reaction functions close to equilibrium, these steady
      state PCr/ATP ratios presumably coincided with about 3-fold higher free adenosine
      diphosphate (ADP) concentrations. Higher ADP concentrations (i.e., lower
      [PCr]/[ATP] ratios) were interpreted to correlate with the Km values for ADP
      requiring kinases of glycolysis and to reflect elevated carbohydrate
      contributions to heart energy needs. This metabolic organization is postulated as
      advantageous in hypobaria because the ATP yield per O2 molecule is 25-60% higher
      with glucose than with free fatty acids (the usual fuels utilized in the human
      heart in postfasting conditions).

PMID- 8577744
TI  - Structure-activity analysis of thanatin, a 21-residue inducible insect defense
      peptide with sequence homology to frog skin antimicrobial peptides.
AB  - Immune challenge to the insect Podisus maculiventris induces synthesis of a 21
      residue peptide with sequence homology to frog skin antimicrobial peptides of the
      brevinin family. The insect and frog peptides have in common a C-terminally
      located disulfide bridge delineating a cationic loop. The peptide is bactericidal
      and fungicidal, exhibiting the largest antimicrobial spectrum observed so far for
      an insect defense peptide. An all-D-enantiomer is nearly inactive against Gram
      negative bacteria and some Gram-positive strains but is fully active against
      fungi and other Gram-positive bacteria, suggesting that more than one mechanism
      accounts for the antimicrobial activity of this peptide. Studies with truncated
      synthetic isoforms underline the role of the C-terminal loop and flanking
      residues for the activity of this molecule for which we propose the name
      thanatin.

PMID- 8577745
TI  - Isolation of an oxygen-sensitive FNR protein of Escherichia coli: interaction at
      activator and repressor sites of FNR-controlled genes.
AB  - The Escherichia coli fnr gene product, FNR, is a DNA binding protein that
      regulates a large family of genes involved in cellular respiration and carbon
      metabolism during conditions of anaerobic cell growth. FNR is believed to contain
      a redox/O2-sensitive element for detecting the anaerobic state. To investigate
      this process, a fnr mutant that encodes an altered FNR protein with three amino
      acid substitutions in the N-terminal domain was constructed by site-directed
      mutagenesis. In vivo, the mutant behaved like a wild-type strain under anaerobic
      conditions but had a 14-fold elevated level of transcriptional activation of a
      reporter gene during aerobic cell growth. The altered fur gene was overexpressed
      in E. coli and the resultant FNR protein was purified to near homogeneity by
      using anaerobic chromatography procedures. An in vitro Rsa I restriction site
      protection assay was developed that allowed for the assessment of oxygen
      dependent DNA binding of the mutant FNR protein. The FNR protein was purified as
      a monomer of M(r) 28,000 that contained nonheme iron at 2.05 +/- 0.34 mol of Fe
      per FNR monomer. In vitro DNase I protection studies were performed to establish
      the locations of the FNR-binding sites at the narG, narK, dmsA, and hemA
      promoters that are regulated by either activation or repression of their
      transcription. The sizes of the DNA footprints are consistent with the binding of
      two monomers of FNR that protect the symmetrical FNR-recognition sequence TTGAT
      nnnnATCAA. Exposure of the FNR protein or protein-DNA complex to air for even
      short periods of time (approximately 5 min) led to the complete loss of DNA
      protection at a consensus FNR recognition site. A model whereby the FNR protein
      exists in the cell as a monomer that assembles on the DNA under anaerobic
      conditions to form a dimer is discussed.

PMID- 8577746
TI  - Cloning of human adenosine kinase cDNA: sequence similarity to microbial
      ribokinases and fructokinases.
AB  - Adenosine kinase catalyzes the phosphorylation of adenosine to AMP and hence is a
      potentially important regulator of extracellular adenosine concentrations.
      Despite extensive characterization of the kinetic properties of the enzyme, its
      primary structure has never been elucidated. Full-length cDNA clones encoding
      catalytically active adenosine kinase were obtained from lymphocyte, placental,
      and liver cDNA libraries. Corresponding mRNA species of 1.3 and 1.8 kb were noted
      on Northern blots of all tissues examined and were attributable to alternative
      polyadenylylation sites at the 3' end of the gene. The encoding protein consists
      of 345 amino acids with a calculated molecular size of 38.7 kDa and does not
      contain any sequence similarities to other well-characterized mammalian
      nucleoside kinases, setting it apart from this family of structurally and
      functionally related proteins. In contrast, two regions were identified with
      significant sequence identity to microbial ribokinase and fructokinases and a
      bacterial inosine/guanosine kinase. Thus, adenosine kinase is a structurally
      distinct mammalian nucleoside kinase that appears to be akin to sugar kinases of
      microbial origin.

PMID- 8577747
TI  - P-glycoprotein confers methotrexate resistance in 3T6 cells with deficient
      carrier-mediated methotrexate uptake.
AB  - P-glycoprotein (Pgp), a transmembrane efflux pump encoded by the MDR1 gene,
      transports various lipophilic drugs that enter the cell by passive diffusion
      through the lipid bilayer. Pgp-expressing multidrug-resistant cell lines are not
      usually cross-resistant to a hydrophilic antifolate methotrexate (MTX). MTX
      enters cells primarily through a folate carrier, but passive diffusion becomes
      the primary mode of MTX uptake in carrier-deficient cells. To test if a
      deficiency in MTX carrier would allow Pgp to confer resistance to MTX, a MTX
      carrier-deficient cell line (3T6-C26) was infected with a recombinant retrovirus
      expressing the human MDR1 gene. The infected 3T6-C26 cells showed increased
      survival in MTX relative to uninfected cells. Multistep selection of the infected
      cells with vinblastine led to increased Pgp expression and a concomitant increase
      in resistance to MTX. MTX resistance of Pgp-expressing 3T6-C26 cells was reduced
      by Pgp inhibitors, including a Pgp-specific monoclonal antibody UTC2. In
      contrast, the expression and the inhibition of Pgp had no effect on MTX
      resistance in 3T6 cells with normal carrier-mediated MTX uptake. Thus, a
      deficiency in the MTX carrier enables Pgp to confer resistance to MTX, suggesting
      that hydrophilic compounds may become Pgp substrates when such compounds enter
      cells by passive diffusion.

PMID- 8577748
TI  - The chicken beta 2-microglobulin gene is located on a non-major
      histocompatibility complex microchromosome: a small, G+C-rich gene with X and Y
      boxes in the promoter.
AB  - beta 2-Microglobulin is an essential subunit of major histocompatibility complex
      (Mhc) class I molecules, which present antigenic peptides to T lymphocytes. We
      sequenced a number of cDNAs and two genomic clones corresponding to chicken beta
      2-microglobulin. The chicken beta 2-microglobulin gene has a similar genomic
      organization but smaller introns and higher G+C content than mammalian beta 2
      microglobulin genes. The promoter region is particularly G+C-rich and contains,
      in addition to interferon regulatory elements, potential S/W, X, and Y boxes that
      were originally described for mammalian class II but not class I alpha or beta 2
      microglobulin genes. There is a single chicken beta 2-microglobulin gene that has
      little polymorphism in the coding region. Restriction fragment length
      polymorphisms from Mhc homozygous lines, Mhc congenic lines, and backcross
      families, as well as in situ hybridization, show that the beta 2-microglobulin
      gene is located on a microchromosome different from the one that contains the
      chicken Mhc. We propose that the structural similarities between the beta 2
      microglobulin and Mhc genes in the chicken are due to their presence on
      microchromosomes and suggest that these features and the microchromosomes
      appeared by deletion of DNA in the lineage leading to the birds.

PMID- 8577749
TI  - Preserved speech abilities and compensation following prefrontal damage.
AB  - Lesions to left frontal cortex in humans produce speech production impairments
      (nonfluent aphasia). These impairments vary from subject to subject and
      performance on certain speech production tasks can be relatively preserved in
      some patients. A possible explanation for preservation of function under these
      circumstances is that areas outside left prefrontal cortex are used to compensate
      for the injured brain area. We report here a direct demonstration of preserved
      language function in a stroke patient (LF1) apparently due to the activation of a
      compensatory brain pathway. We used functional brain imaging with positron
      emission tomography (PET) as a basis for this study.

PMID- 8577750
TI  - The secreted Ipa complex of Shigella flexneri promotes entry into mammalian
      cells.
AB  - The bacterial pathogen Shigella flexneri causes bacillary dysentery in humans by
      invading coloncytes. Upon contact with epithelial cells, S. flexneri elicits
      localized plasma membrane projections sustained by long actin filaments which
      engulf the microorganism. The products necessary for Shigella entry include three
      secretory proteins: IpaB, IpaC, and IpaD. Extracellular IpaB and IpaC associate
      in a soluble complex, the Ipa complex. We have immunopurified this Ipa complex on
      latex beads and found that they were efficiently internalized into HeLa cells.
      Like S. flexneri entry, uptake of the beads bearing the Ipa complex was
      associated with membrane projections and polymerization of actin at the site of
      cell-bead interaction and was dependent on small Rho GTPases. These results
      indicate that a secreted factor can promote S. flexneri entry into epithelial
      cells.

PMID- 8577751
TI  - Helicobacter pylori attachment to gastric cells induces cytoskeletal
      rearrangements and tyrosine phosphorylation of host cell proteins.
AB  - The consequences of Helicobacter pylori attachment to human gastric cells were
      examined by transmission electron microscopy and immunofluorescence microscopy.
      H. pylori attachment resulted in (i) effacement of microvilli at the site of
      attachment, (ii) cytoskeletal rearrangement directly beneath the bacterium, and
      (iii) cup/pedestal formation at the site of attachment. Double-immunofluorescence
      studies revealed that the cytoskeletal components actin, alpha-actinin, and talin
      are involved in the process. Immunoblot analysis showed that binding of H. pylori
      to AGS cells induced tyrosine phosphorylation of two host cell proteins of 145
      and 105 kDa. These results indicate that attachment of H. pylori to gastric
      epithelial cells resembles that of enteropathogenic Escherichia coli. Coccoid H.
      pylori, which are thought to be terminally differentiated bacterial forms, are
      capable of binding and inducing cellular changes of the same sort as spiral H.
      pylori, including tyrosine phosphorylation of host proteins.

PMID- 8577752
TI  - A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal
      protein with a specific expression pattern.
AB  - Adrenoleukodystrophy (ALD), a severe demyelinating disease, is caused by
      mutations in a gene coding for a peroxisomal membrane protein (ALDP), which
      belongs to the superfamily of ATP binding cassette (ABC) transporters and has the
      structure of a half transporter. ALDP showed 38% sequence identity with another
      peroxisomal membrane protein, PMP70, up to now its closest homologue. We describe
      here the cloning and characterization of a mouse ALD-related gene (ALDR), which
      codes for a protein with 66% identity with ALDP and shares the same half
      transporter structure. The ALDR protein was overexpressed in COS cells and was
      found to be associated with the peroxisomes. The ALD and ALDR genes show
      overlapping but clearly distinct expression patterns in mouse and may thus play
      similar but nonequivalent roles. The ALDR gene, which appears highly conserved in
      man, is a candidate for being a modifier gene that could account for some of the
      extreme phenotypic variability of ALD. The ALDR gene is also a candidate for
      being implicated in one of the complementation groups of Zellweger syndrome, a
      genetically heterogeneous disorder of peroxisome biogenesis, rare cases of which
      were found to be associated with mutations in the PMP70 (PXMP1) gene.

PMID- 8577753
TI  - Neuronal abnormalities in microtubule-associated protein 1B mutant mice.
AB  - Microtubules play an important role in establishing cellular architecture.
      Neuronal microtubules are considered to have a role in dendrite and axon
      formation. Different portions of the developing and adult brain microtubules are
      associated with different microtubule-associated proteins (MAPs). The roles of
      each of the different MAPs are not well understood. One of these proteins, MAP1B,
      is expressed in different portions of the brain and has been postulated to have a
      role in neuronal plasticity and brain development. To ascertain the role of
      MAP1B, we generated mice which carry an insertion in the gene by gene-targeting
      methods. Mice which are homozygous for the modification die during embryogenesis.
      The heterozygotes exhibit a spectrum of phenotypes including slower growth rates,
      lack of visual acuity in one or both eyes, and motor system abnormalities.
      Histochemical analysis of the severely affected mice revealed that their Purkinje
      cell dendritic processes are abnormal, do not react with MAP1B antibodies, and
      show reduced staining with MAP1A antibodies. Similar histological and
      immunochemical changes were observed in the olfactory bulb, hippocampus, and
      retina, providing a basis for the observed phenotypes.

PMID- 8577755
TI  - A technique for detecting matrix proteins in the crystalline spicule of the sea
      urchin embryo.
AB  - The presence of proteins associated with the CaCO3-containing biocrystals found
      in a wide variety of marine organisms is well established. In these organisms,
      including the primitive skeleton (spicule) of the sea urchin embryo, the
      structural and functional role of these proteins either in the biomineralization
      process or in control of the structural features of the biocrystals is unclear.
      Recently, one of the matrix proteins of the sea urchin spicule, SM 30, has been
      shown to contain a carbohydrate chain (the 1223 epitope) that has been implicated
      in the process whereby Ca2+ is deposited as CaCo3. Because an understanding of
      the localization of this protein, as well as other proteins found within the
      spicule, is central to understanding their function, we undertook to develop
      methods to localize spicule matrix proteins in intact spicules, using immunogold
      techniques and scanning electron microscopy. Gold particles indicative of this
      matrix glycoprotein could not be detected on the surface of spicules that had
      been isolated from embryo homogenates and treated with alkaline hypochlorite to
      remove any associated membranous material. However, when isolated spicules were
      etched for 2 min with dilute acetic acid (10 mM) to expose more internal regions
      of the crystal, SM 30 and perhaps other proteins bearing the 1223 carbohydrate
      epitope were detected in the calcite matrix. These results, indicating that these
      two antigens are widely distributed in the spicule, suggest that this technique
      should be applicable to any matrix protein for which antibodies are available.

PMID- 8577754
TI  - Substance P responsiveness of smooth muscle cells is regulated by the integrin
      ligand, thrombospondin.
AB  - The extracellular factors that determine a cell's responsiveness to
      neurotransmitters are of particular relevance for pharmacologically diverse cell
      types such as neurons and smooth muscle. We previously demonstrated that matrix
      associated factors are capable of dramatically and specifically suppressing the
      responsiveness of smooth muscle to the neuropeptide, substance P. We now
      demonstrate that this influence of extracellular matrix on the pharmacological
      phenotype of smooth muscle cells can be blocked specifically by an Arg-Gly-Asp
      (RGD)-containing antagonist of integrins. Of a battery of integrin ligands
      tested, only thrombospondin mimicked the effect of the extracellular matrix on
      substance P responsiveness. This effect of thrombospondin was dose dependent, RGD
      sensitive, and blocked by an antibody directed against the RGD-containing region
      of thrombospondin. Because the mRNA for thrombospondin is present in the cells of
      the chicken amnion, this extracellular factor may normally suppress substance P
      responsiveness in amniotic smooth muscle. The results suggest a role for matrix
      associated integrin ligands in the regulation of cellular responses to specific
      neurotransmitters and hormones and in the development and maintenance of tissue
      specific pharmacological properties.

PMID- 8577756
TI  - Heteromeric connexons in lens gap junction channels.
AB  - Gap junction channels are formed by paired oligomeric membrane hemichannels
      called connexons, which are composed of proteins of the connexin family.
      Experiments with transfected cell lines and paired Xenopus oocytes have
      demonstrated that heterotypic intercellular channels which are formed by two
      connexons, each composed of a different connexin, can selectively occur. Studies
      by Stauffer [Stauffer, K. A. (1995) J. Biol. Chem. 270, 6768-6772] have shown
      that recombinant Cx26 and Cx32 coinfected into insect cells may form heteromeric
      connexons. By solubilizing and subfractionating individual connexons from ovine
      lenses, we show by immunoprecipitation that connexons can contain two different
      connexins forming heteromeric assemblies in vivo.

PMID- 8577757
TI  - Products of DNA mismatch repair genes mutS and mutL are required for
      transcription-coupled nucleotide-excision repair of the lactose operon in
      Escherichia coli.
AB  - To improve our understanding of the mechanism that couples nucleotide-excision
      repair to transcription in expressed genes, we have examined the effects of
      mutations in several different DNA repair genes on the removal of cyclobutane
      pyrimidine dimers from the individual strands of the induced lactose operon in UV
      irradiated Escherichia coli. As expected, we found little repair in either strand
      of the lactose operon in strains with mutations in established nucleotide
      excision-repair genes (uvrA, uvrB, uvrC, or uvrD). In contrast, we found that
      mutations in either of two genes required for DNA-mismatch correction (mutS and
      mutL) selectively abolish rapid repair in the transcribed strand and render the
      cells moderately sensitive to UV irradiation. Similar results were found in a
      strain with a mutation in the mfd gene, the product of which has been previously
      shown to be required for transcription-coupled repair in vitro. Our results
      demonstrate an association between mismatch-correction and nucleotide-excision
      repair and implicate components of DNA-mismatch repair in transcription-coupled
      repair. In addition, they may have important consequences for human disease and
      may enhance our understanding of the etiology of certain cancers which have been
      associated with defects in mismatch correction.

PMID- 8577758
TI  - A compositional map of human chromosome band Xq28.
AB  - The molar fractions of guanine plus cytosine (GC) in DNA were determined for 36
      yeast artificial chromosomes (YACs) which almost completely cover human
      chromosome band Xq28, a terminal reverse band, corresponding to about 8 Mb of
      DNA. This allowed the construction of the most complete compositional map to date
      of a chromosomal band; three regions were observed: (i) a proximal 3.5-Mb region
      formed by GC-poor L and GC-rich H1 isochores; (ii) a middle 2,2-Mb region
      essentially formed by a GC-rich H2 isochore and a very GC-rich H3 isochore
      separated by a GC-poor L isochore, YACs from this region being characterized by a
      striking compositional heterogeneity and instability; and (iii) a distal 1.3-Mb
      region exclusively formed by GC-poor L isochores. Gene and CpG island
      concentrations increased with the GC levels of the isochores, as expected. Xq28
      exemplifies a subset of reverse bands which are different from the two other
      subsets, namely from telomeric bands, which are characterized by specific
      cytogenetic properties and by the predominance of H2 and H3 isochores, and from
      the majority of reverse bands, which do not contain H2 and H3 isochores.

PMID- 8577759
TI  - Lens complementation system for the genetic analysis of growth, differentiation,
      and apoptosis in vivo.
AB  - A genetic approach has been established that combines the advantages of
      blastocyst complementation with the experimental attributes of the developing
      lens for the functional analysis of genes governing cellular proliferation,
      terminal differentiation, and apoptosis. This lens complementation system (LCS)
      makes use of a mutant mouse strain, aphakia (ak), homozygotes of which fail to
      develop an ocular lens. We demonstrate that microinjection of wild-type embryonic
      stem (ES) cells into ak/ak blastocysts produces chimeras with normal ES-cell
      derived lenses and that microinjection of Rb-/- ES cells generates an aberrant
      lens phenotype identical to that obtained through conventional gene targeting
      methodology. Our determination that a cell autonomous defect underlies the
      aphakia condition assures that lenses generated through LCS are necessarily ES
      cell-derived. LCS provides for the rapid phenotypic analysis of loss-of-function
      mutations, circumvents the need for germ-line transmission of null alleles, and,
      most significantly, facilitates the study of essential genes whose inactivation
      is associated with early lethal phenotypes.

PMID- 8577760
TI  - Antiproliferative properties of the USF family of helix-loop-helix transcription
      factors.
AB  - USF is a family of transcription factors characterized by a highly conserved
      basic-helix-loop-helix-leucine zipper (bHLH-zip) DNA-binding domain. Two
      different USF genes, termed USF1 and USF2, are ubiquitously expressed in both
      humans and mice. The USF1 and USF2 proteins contain highly divergent
      transcriptional activation domains but share extensive homologies in the bHLH-zip
      region and recognize the same CACGTG DNA motifs. Although the DNA-binding and
      transcriptional activities of these proteins have been characterized, the
      biological function of USF is not well understood. Here, focus- and colony
      formation assays were used to investigate the potential involvement of USF in the
      regulation of cellular transformation and proliferation. Both USF1 and USF2
      inhibited the transformation of rat embryo fibroblasts mediated by Ras and c-Myc,
      a bHLH-zip transcription factor that also binds CACGTG motifs. DNA binding was
      required but not fully sufficient for inhibition of Myc-dependent transformation
      by USF, since deletion mutants containing only the DNA-binding domains of USF1 or
      USF2 produced partial inhibition. While the effect of USF1 was selective for Myc
      dependent transformation, wild-type USF2 exerted in addition a strong inhibition
      of E1A-mediated transformation and a strong suppression of HeLa cell colony
      formation. These results suggest that members of the USF family may serve as
      negative regulators of cellular proliferation in two ways, one by antagonizing
      the transforming function of Myc, the other through a more general growth
      inhibitory effect.

PMID- 8577761
TI  - Transfer of beta-amyloid precursor protein gene using adenovirus vector causes
      mitochondrial abnormalities in cultured normal human muscle.
AB  - As in Alzheimer-disease (AD) brain, vacuolated muscle fibers of inclusion-body
      myositis (IBM) contain abnormally accumulated beta-amyloid precursor protein
      (beta APP), including its beta-amyloid protein epitope, and increased beta APP
      751 mRNA. Other similarities between IBM muscle and AD brain phenotypes include
      paired helical filaments, hyperphosphorylated tau protein, apolipoprotein E, and
      mitochondrial abnormalities, including decreased cytochrome-c oxidase (COX)
      activity. The pathogenesis of these abnormalities in IBM muscle and AD brain is
      not known. We now report that direct transfer of the beta APP gene, using
      adenovirus vector, into cultured normal human muscle fibers causes structural
      abnormalities of mitochondria and decreased COX activity. In this adenovirus
      mediated beta APP gene transfer, we demonstrated that beta APP overproduction can
      induce mitochondrial abnormalities. The data suggest that excessive beta APP may
      be responsible for mitochondrial and COX abnormalities in IBM muscle and perhaps
      AD brain.

PMID- 8577762
TI  - Efficient generation of recombinant adenoviruses using adenovirus DNA-terminal
      protein complex and a cosmid bearing the full-length virus genome.
AB  - An efficient method of constructing recombinant adenoviruses (Ads) has been
      established. The expression unit to be introduced into recombinant Ad was first
      inserted into the unique Swa I site of the full-length Ad genome cloned in a
      cassette cosmid. The cassette bearing the expression unit was then cotransfected
      into human embryonic kidney 293 cells together with the Ad DNA-terminal protein
      complex digested at several sites with Eco T22I or Ase I/EcoRI. The use of the
      parent Ad DNA-terminal protein complex instead of the deproteinized Ad genome DNA
      allowed very efficient recovery of the desired recombinant Ad, and the above
      restriction digestion drastically reduced regeneration of the parent virus.
      Several hundred virus clones were readily obtained in each experiment, and about
      70% of the clones were the desired recombinant viruses. Furthermore, because the
      cassette contained the full-length Ad genome, any position of the genome could be
      easily modified to develop a new vector design. We established construction
      systems for two types of Ad vectors, the E1-substitution type and the E4
      insertion type. This method may greatly facilitate the application of recombinant
      Ads and should be useful for further improvement of Ad vectors.

PMID- 8577763
TI  - Increased dopamine turnover in the prefrontal cortex impairs spatial working
      memory performance in rats and monkeys.
AB  - The selective activation of the prefrontal cortical dopamine system by mild
      stress can be mimicked by anxiogenic beta-carbolines such as FG7142. To
      investigate the functional relevance of elevated levels of dopamine turnover in
      the prefrontal cortex, the current study examined the effects of FG7142 on the
      performance of spatial working memory tasks in the rat and monkey. FG7142
      selectively increased prefrontal cortical dopamine turnover in rats and
      significantly impaired performance on spatial working memory tasks in both rats
      and monkeys. Spatial discrimination, a task with similar motor and motivational
      demands (rats), or delayed response performance following zero-second delays
      (monkeys) was unaffected by FG7142. Further, biochemical analysis in rats
      revealed a significant positive correlation between dopamine turnover in the
      prefrontal cortex and cognitive impairment on the delayed alternation task. The
      cognitive deficits in both rats and monkeys were prevented by pretreatment with
      the benzodiazepine receptor antagonist, RO15-1788, which blocked the increase in
      dopamine turnover and by the dopamine receptor antagonists, haloperidol,
      clozapine, and SCH23390. These findings indicate that excessive dopamine activity
      in the prefrontal cortex is detrimental to cognitive functions mediated by the
      prefrontal cortex.

PMID- 8577764
TI  - Synergy between chronic corticosterone and sodium azide treatments in producing a
      spatial learning deficit and inhibiting cytochrome oxidase activity.
AB  - Previously, we developed a rat model of persistent mitochondrial dysfunction
      based upon the chronic partial inhibition of the mitochondrial enzyme cytochrome
      oxidase (EC 1.9.3.1). Continuous systemic infusion of sodium azide at
      approximately 1 mg/kg per hr inhibited cytochrome oxidase activity and produced a
      spatial learning deficit. In other laboratories, glucocorticoids have been
      reported to exacerbate neuronal damage from various acute metabolic insults.
      Therefore, we tested the hypothesis that corticosterone, the primary
      glucocorticoid in the rat, would potentiate the sodium azide-induced learning
      deficit. To this end, we first identified nonimpairing doses of sodium azide
      (approximately 0.75 mg/kg per hr) and corticosterone (100-mg pellet, 3-week
      sustained-release). We now report that chronic co-administration of these
      individually nonimpairing treatments produced a severe learning deficit.
      Moreover, the low dose of corticosterone, which did not elevate serum
      corticosterone, acted synergistically with sodium azide to inhibit cytochrome
      oxidase activity. The latter result represents a previously unidentified effect
      of glucocorticoids that provides a candidate mechanism for glucocorticoid
      potentiation of neurotoxicity induced by metabolic insult. These results may have
      the clinical implication of expanding the definition of hypercortisolism in
      patient populations with compromised oxidative metabolism. Furthermore, they
      suggest that glucocorticoid treatment may contribute to pathology in disease or
      trauma conditions that involve metabolic insult.

PMID- 8577765
TI  - Short-term synaptic enhancement and long-term potentiation in neocortex.
AB  - Repetitive stimuli reliably induce long-term potentiation (LTP) of synapses in
      the upper layers of the granular somatosensory cortex but not the agranular motor
      cortex of rats. Herein we examine, in these same cortical areas, short-term
      changes in synaptic strength that occur during the LTP induction period. theta
      Burst stimulation produced a strong short-term enhancement of synapses in the
      granular area but only weak enhancement in the agranular area. The magnitude of
      enhancement during stimulation was strongly correlated with the magnitude of LTP
      subsequently expressed. Short-term enhancement was abolished by an antagonist of
      N-methyl-D-aspartate (NMDA) receptors but remained in the presence of a non-NMDA
      receptor antagonist. Inhibitory postsynaptic potentials of the granular and
      agranular areas displayed similar frequency sensitivity, but the frequency
      sensitivity of NMDA receptor-dependent excitatory postsynaptic potentials
      differed significantly between areas. We propose that pathway-specific
      differences in short-term enhancement are due to variations in the frequency
      dependence of NMDA currents; different capacities for short-term enhancement may
      explain why repetitive stimulation more readily induces LTP in the somatosensory
      cortex than in the motor cortex.

PMID- 8577767
TI  - Cue recognition and cue elaboration in learning from examples.
AB  - This paper describes the processes used by students to learn from worked-out
      examples and by working through problems. Evidence is derived from protocols of
      students learning secondary school mathematics and physics. The students acquired
      knowledge from the examples in the form of productions (condition-->action):
      first discovering conditions under which the actions are appropriate and then
      elaborating the conditions to enhance efficiency. Students devoted most of their
      attention to the condition side of the productions. Subsequently, they
      generalized the productions for broader application and acquired specialized
      productions for special problem classes.

PMID- 8577766
TI  - Role of guanine nucleotide-binding proteins--ras-family or trimeric proteins or
      both--in Ca2+ sensitization of smooth muscle.
AB  - The purpose of this study was to identify guanine nucleotide-binding proteins (G
      proteins) involved in the agonist- and guanosine 5'-[gamma-thio]triphosphate
      (GTP[gamma-S])-induced increase in the Ca2+ sensitivity of 20-kDa myosin light
      chain (MLC20) phosphorylation and contraction in smooth muscle. A constitutively
      active, recombinant val14p21rhoA.GTP expressed in the baculovirus/Sf9 system, but
      not the protein expressed without posttranslational modification in Escherichia
      coli, induced at constant Ca2+ (pCa 6.4) a slow contraction associated with
      increased MLC20 phosphorylation from 19.8% to 29.5% (P < 0.05) in smooth muscle
      permeabilized with beta-esein. The effect of val14p21rhoA.GTP was inhibited by
      ADP-ribosylation of the protein and was absent in smooth muscle extensively
      permeabilized with Triton X-100. ADP-ribosylation of endogenous p21rho with
      epidermal cell differentiation inhibitor (EDIN) inhibited Ca2+ sensitization
      induced by GTP [in rabbit mesenteric artery (RMA) and rabbit ileum smooth
      muscles], by carbachol (in rabbit ileum), and by endothelin (in RMA), but not by
      phenylephrine (in RMA), and only slowed the rate without reducing the amplitude
      of contractions induced in RMA by 1 microM GTP[gamma-S] at constant Ca2+
      concentrations. AlF(4-)-induced Ca2+ sensitization was inhibited by both
      guanosine 5'-[beta-thio]diphosphate (GDP[beta-S]) and by EDIN. EDIN also
      inhibited, to a lesser extent, contractions induced by Ca2+ alone (pCa 6.4) in
      both RMA and rabbit ileum. ADP-ribosylation of trimeric G proteins with pertussis
      toxin did not inhibit Ca2+ sensitization. We conclude that p21rho may play a role
      in physiological Ca2+ sensitization as a cofactor with other messengers, rather
      than as a sole direct inhibitor of smooth muscle MLC20 phosphatase.

PMID- 8577768
TI  - Extending the chemistry that supports genetic information transfer in vivo:
      phosphorothioate DNA, phosphorothioate RNA, 2'-O-methyl RNA, and
      methylphosphonate DNA.
AB  - DNA and RNA are the polynucleotides known to carry genetic information in life.
      Chemical variants of DNA and RNA backbones have been used in structure-function
      and biosynthesis studies in vitro, and in antisense pharmacology, where their
      properties of nuclease resistance and enhanced cellular uptake are important.
      This study addressed the question of whether the base(s) attached to artificial
      backbones encodes genetic information that can be transferred in vivo.
      Oligonucleotides containing chemical variants of DNA or RNA were used as primers
      for site-specific mutagenesis of bacteriophage f1. Progeny phage were scored both
      genetically and physically for the inheritance of information originally encoded
      by bases attached to the nonstandard backbones. Four artificial backbone
      chemistries were tested: phosphorothioate DNA, phosphorothioate RNA, 2'-O-methyl
      RNA and methylphosphonate DNA. All four were found capable of faithful
      information transfer from their attached bases when one or three artificial
      positions were flanked by normal DNA. Among oligonucleotides composed entirely of
      nonstandard backbones, only phosphorothioate DNA supported genetic information
      transfer in vivo.

PMID- 8577769
TI  - Identification of residues that control specific binding of the Shc
      phosphotyrosine-binding domain to phosphotyrosine sites.
AB  - The Shc adaptor protein contains two phosphotyrosine [Tyr(P)]binding modules--an
      N-terminal Tyr(P) binding (PTB) domain and a C-terminal Src homology 2 (SH2)
      domain. We have compared the ability of the Shc PTB domain to bind the receptors
      for nerve growth factor and insulin, both of which contain juxtamembrane Asn-Pro
      Xaa-Tyr(P) motifs implicated in PTB binding. The Shc PTB domain binds with high
      affinity to a phosphopeptide corresponding to the nerve growth factor receptor
      Tyr-490 autophosphorylation site. Analysis of individual residues within this
      motif indicates that the Asn at position -3 [with respect to Tyr(P)], in addition
      to Tyr(P), is critical for PTB binding, while the Pro at position -2 plays a less
      significant role. A hydrophobic amino acid 5 residues N-terminal to the Tyr(P) is
      also essential for high-affinity binding. In contrast, the Shc PTB domain does
      not bind stably to the Asn-Pro-Xaa-Tyr(P) site at Tyr-960 in the activated
      insulin receptor, which has a polar residue (Ser) at position -5. Substitution of
      this Ser at position -5 with Ile markedly increased binding of the insulin
      receptor Tyr-960 phosphopeptide to the PTB domain. These results suggest that
      while the Shc PTB domain recognizes a core sequence of Asn-Pro-Xaa-Tyr(P), its
      binding affinity is modulated by more N-terminal residues in the ligand, which
      therefore contribute to the specificity of PTB-receptor interactions. An analysis
      of residues in the Shc PTB domain required for binding to Tyr(P) sites identified
      a specific and evolutionarily conserved Arg (Arg-175) that is uniquely important
      for ligand binding and is potentially involved in Tyr(P) recognition.

PMID- 8577770
TI  - The in vitro ejection of zinc from human immunodeficiency virus (HIV) type 1
      nucleocapsid protein by disulfide benzamides with cellular anti-HIV activity.
AB  - Several disulfide benzamides have been shown to possess wide-spectrum
      antiretroviral activity in cell culture at low micromolar to submicromolar
      concentrations, inhibiting human immunodeficiency virus (HIV) type 1 (HIV-1)
      clinical and drug-resistant strains along with HIV-2 and simian immunodeficiency
      virus [Rice, W. G., Supko, J. G., Malspeis, L., Buckheit, R. W., Jr., Clanton,
      D., Bu, M., Graham, L., Schaeffer, C. A., Turpin, J. A., Domagala, J., Gogliotti,
      R., Bader, J. P., Halliday, S. M., Coren, L., Sowder, R. C., II, Arthur, L. O. &
      Henderson, L. E. (1995) Science 270, 1194-1197]. Rice and coworkers have proposed
      that the compounds act by "attacking" the two zinc fingers of HIV nucleocapsid
      protein. Shown here is evidence that low micromolar concentrations of the anti
      HIV disulfide benzamides eject zinc from HIV nucleocapsid protein (NCp7) in
      vitro, as monitored by the zinc-specific fluorescent probe N-(6-methoxy-8
      quinoyl)-p-toluenesulfonamide (TSQ). Structurally similar disulfide benzamides
      that do not inhibit HIV-1 in culture do not eject zinc, nor do analogs of the
      antiviral compounds with the disulfide replaced with a methylene sulfide. The
      kinetics of NCp7 zinc ejection by disulfide benzamides were found to be
      nonsaturable and biexponential, with the rate of ejection from the C-terminal
      zinc finger 7-fold faster than that from the N-terminal. The antiviral compounds
      were found to inhibit the zinc-dependent binding of NCp7 to HIV psi RNA, as
      studied by gel-shift assays, and the data correlated well with the zinc ejection
      data. Anti-HIV disulfide benzamides specifically eject NCp7 zinc and abolish the
      protein's ability to bind psi RNA in vitro, providing evidence for a possible
      antiretroviral mechanism of action of these compounds. Congeners of this class
      are under advanced preclinical evaluation as a potential chemotherapy for
      acquired immunodeficiency syndrome.

PMID- 8577771
TI  - Improved antitumor activity of a recombinant anti-Lewis(y) immunotoxin not
      requiring proteolytic activation.
AB  - B1(dsFv)-PE33 is a recombinant immunotoxin composed of a mutant form of
      Pseudomonas exotoxin (PE) that does not need proteolytic activation and a
      disulfide-stabilized Fv fragment of the anti-Lewis(y) monoclonal antibody B1,
      which recognizes a carbohydrate epitope on human carcinoma cells. In this
      molecule, amino acids 1-279 of PE are deleted and domain Ib (amino acids 365-394)
      is replaced by the heavy chain variable region (VH) domain of monoclonal antibody
      B1. The light chain (VL) domain is connected to the VH domain by a disulfide
      bond. This recombinant toxin, termed B1(dsFv)-PE33, does not require proteolytic
      activation and it is smaller than other immunotoxins directed at Lewis(y), all of
      which require proteolytic activation. Furthermore, it is more cytotoxic to
      antigen-positive cell lines. B1(dsFv)-PE38 has the highest antitumor activity of
      anti-Lewis(y) immunotoxins previously constructed. B1(dsFv)-PE33 caused complete
      regression of tumors when given at 12 micrograms/kg (200 pmol/kg) every other day
      for three doses, whereas B1(dsFv)-PE38 did not cause regressions at 13
      micrograms/kg (200 pmol/kg). By bypassing the need for proteolytic activation and
      decreasing molecular size we have enlarged the therapeutic window for the
      treatment of human cancers growing in mice, so that complete remissions are
      observed at 2.5% of the LD50.

PMID- 8577772
TI  - In vivo anergized CD4+ T cells express perturbed AP-1 and NF-kappa B
      transcription factors.
AB  - Anergy is a major mechanism to ensure antigen-specific tolerance in T lymphocytes
      in the adult. In vivo, anergy has mainly been studied at the cellular level. In
      this study, we used the T-cell-activating superantigen staphylococcal enterotoxin
      A (SEA) to investigate molecular mechanisms of T-lymphocyte anergy in vivo.
      Injection of SEA to adult mice activates CD4+ T cells expressing certain T-cell
      receptor (TCR) variable region beta-chain families and induces strong and rapid
      production of interleukin 2 (IL-2). In contrast, repeated injections of SEA cause
      CD4+ T-cell deletion and anergy in the remaining CD4+ T cells, characterized by
      reduced expression of IL-2 at mRNA and protein levels. We analyzed expression of
      AP-1, NF-kappa B, NF-AT, and octamer binding transcription factors, which are
      known to be involved in the regulation of IL-2 gene promoter activity. Large
      amounts of AP-1 and NF-kappa B and significant quantities of NF-AT were induced
      in SEA-activated CD4+ spleen T cells, whereas Oct-1 and Oct-2 DNA binding
      activity was similar in both resting and activated T cells. In contrast, anergic
      CD4+ T cells contained severely reduced levels of AP-1 and Fos/Jun-containing NF
      AT complexes but expressed significant amounts of NF-kappa B and Oct binding
      proteins after SEA stimulation. Resolution of the NF-kappa B complex demonstrated
      predominant expression of p50-p65 heterodimers in activated CD4+ T cells, while
      anergic cells mainly expressed the transcriptionally inactive p50 homodimer.
      These alterations of transcription factors are likely to be responsible for
      repression of IL-2 in anergic T cells.

PMID- 8577773
TI  - Antigenic variation and the within-host dynamics of parasites.
AB  - Many parasites exhibit antigenic variation within their hosts. We use
      mathematical models to investigate the dynamical interaction between an
      antigenically varying parasite and the host's immune system. The models
      incorporate antigenic variation in the parasite population and the generation of
      immune responses directed against (i) antigens specific to individual parasite
      variants and (ii) antigens common to all the parasite variants. Analysis of the
      models allows us to evaluate the relative importance of variant-specific and
      cross-reactive immune responses in controlling the parasite. Early in the course
      of infection within the host, when parasite diversity is below a defined
      threshold value (the value is determined by the biological properties of the
      parasite and of the host's immune response), the variant-specific immune
      responses are predominant. Later, when the parasite diversity is high, the cross
      reactive immune response is largely responsible for controlling the parasitemia.
      It is argued that increasing antigenic diversity leads to a switch from variant
      specific to cross-reactive immune responses. These simple models mimic various
      features of observed infections recorded in the experimental literature,
      including an initial peak in parasitemia, a long and variable duration of
      infection with fluctuating parasitemia that ends with either the clearance of the
      parasite or persistent infection.

PMID- 8577774
TI  - Equine rhinovirus 1 is more closely related to foot-and-mouth disease virus than
      to other picornaviruses.
AB  - Equine rhinovirus 1 (ERhV1) is a respiratory pathogen of horses which has an
      uncertain taxonomic status. We have determined the nucleotide sequence of the
      ERhV1 genome except for a small region at the 5' end. The predicted polyprotein
      was encoded by 6741 nucleotides and possessed a typical picornavirus proteolytic
      cleavage pattern, including a leader polypeptide. The genomic structure and
      predicted amino acid sequence of ERhV1 were more similar to those of foot-and
      mouth disease viruses (FMDVs), the only members of the aphthovirus genus, than to
      those of other picornaviruses. Features which were most similar to FMDV included
      a 16-amino acid 2A protein which was 87.5% identical in sequence of FMDV 2A, a
      leader (L) protein similar in size to FMDV Lab and the possibility of a truncated
      L protein similar in size to FMDV Lb, and a 3C protease which recognizes
      different cleavage sites. However, unlike FMDV, ERhV1 had only one copy of the 3B
      (VPg) polypeptide. The phylogenetic relationships of the ERhV1 sequence and
      nucleotide sequences of representative species of the five genera of the family
      Picornaviridae were examined. Nucleotide sequences coding for the complete
      polyprotein, the RNA polymerase, and VP1 were analyzed separately. The
      phylogenetic trees confirmed that ERhV1 was more closely related to FMDV than to
      other picornaviruses and suggested that ERhV1 may be a member, albeit very
      distant, of the aphthovirus genus.

PMID- 8577775
TI  - Transcription of tufA and other chloroplast-encoded genes is controlled by a
      circadian clock in Chlamydomonas.
AB  - Levels of mRNA for the chloroplast-encoded elongation factor Tu (tufA) showed a
      dramatic daily oscillation in the green alga Chlamydomonas reinhardtii, peaking
      once each day in the early light period. The oscillation of tufA mRNA levels
      continued in cells shifted to continuous light or continuous dark for at least 2
      3 days. Run-off transcription analyses showed that the rate of tufA transcription
      also peaked early in the light period and, moreover, that this transcriptional
      oscillation continued in cells shifted to continuous conditions. The half-life of
      tufA mRNA was estimated at different times and found to vary considerably during
      a light-dark cycle but not in cells shifted to continuous light. Light-dark
      patterns of transcription of several other chloroplast-encoded genes were
      examined and also found to persist in cells shifted to continuous light or dark.
      These results indicate that a circadian clock controls the transcription of tufA
      and other chloroplast-encoded genes.

PMID- 8577776
TI  - Monthly prostaglandin bibliography prepared by the University of Sheffield
      Biomedical Information Service.

PMID- 8577777
TI  - Arachidonic acid and eicosanoids as targets and effectors in second messenger
      interactions.

PMID- 8577778
TI  - Effect of high potassium diets on the vascular and renal prostaglandin system in
      stroke-prone spontaneously hypertensive rats.
AB  - High potassium (K) diets are known to have a protective effect on the endothelium
      and the kidney against hypertensive injury independent of blood pressure change.
      Vasodepressor prostaglandins (PGs) have been shown to be cytoprotective in
      various tissues. This study investigated the effect of high K diets on the
      vascular and renal eicosanoid system in stroke-prone spontaneously hypertensive
      rats (SHRsp). Eicosanoid production by the aorta and eicosanoid content in the
      renal cortex were examined in SHRsp rats fed high NaCl diets containing either
      0.5% K (normal) or 2.1% K (high). Although the high K diet did not affect the
      blood pressure, SHRsp on the high K diet had less thickening of the aortic wall
      than SHRsp on the normal K diet (-15%, p < 0.001). The aortic strip of the high K
      SHRsp produced less vasodepressor PG than that of the normal K SHRsp when they
      were incubated in a medium (PGI2 -45%, p < 0.003; PGE2 -34%, p < 0.001).
      Furthermore, when the aorta was perfused in a chamber at hypertensive pressure,
      again the high K aorta showed reduced PGI2 production as compared with the normal
      K aorta (intravascular side -52%, p < 0.01). Eicosanoid content in the renal
      cortex was not significantly different between the normal K and the high K SHRsp
      (PGI2 79 vs 87 ng/g dry weight; PGE2 214 vs 233 ng/g dry weight). Thus, the high
      K diet reduced vascular eicosanoid production but did not alter eicosanoid
      content in the renal cortex. The reduced vascular eicosanoid production in the
      high K SHRsp may reflect the reduced necessity for cytoprotective vasodepressor
      PG against vascular injuries.

PMID- 8577779
TI  - Prostaglandin synthesis by cumulus-oocyte complexes: effects on in vitro
      fertilization in mice.
AB  - Cumulus-oocyte complexes, obtained from superovulated Balb/C virgin female mice,
      released to the incubation media significant amounts of PGE1, PGE2 and PGF2
      alpha, as estimated by bioassay. Fertilization rates in vitro decreased sharply
      when cumulus-oocyte complexes were treated with indomethacin (10(-6) M) and then
      inseminated with 5000 sperm per oocyte. In order to explore if the reduced
      prostaglandin (PG) concentration was responsible for diminished fertilization
      rates, PGE1, PGE2 and PGF2 alpha (10(-9) M) were added to the fertilization media
      of treated oocytes. PGE1 and PGE2 but not PGF2 alpha returned fertilization rates
      to control levels. Besides, PGE1 (10(-9) M) enhanced fertilization rates with
      reduced sperm numbers (1000 sperm per oocyte) of untreated cumulus-oocyte
      complexes. In conclusion, PG synthesis and release of mouse cumulus-oocyte
      complexes affects fertilization in vitro, and it is suggested that PGs of the E
      series modulate sperm function at the moment of fertilization.

PMID- 8577780
TI  - Role of interferon-alpha in arachidonic acid metabolism by the rat uteri from
      spayed animals: effect of 17 beta-estradiol.
AB  - Interferon-like trophoblastic proteins modulate prostaglandin (PG) synthesis from
      endometrium in early ovine and bovine pregnancy. We attempted to explore the
      effect of interferon (IFN)-alpha in the isolated rat uterus from ovariectomized
      animals on the metabolism of labelled arachidonic acid (AA). The experiments were
      performed with uterine preparations isolated from spayed rats treated or
      untreated with 17 beta-estradiol prior to sacrifice. The pre-incubation of
      uterine tissue isolated from ovariectomized rats with three different doses (4,
      150 and 300 IU/ml) of IFN-alpha decreased the radioconversion of [14C]AA into 6
      keto PGF1 alpha, PGF2 alpha and PGE2, whereas the formation of thromboxane B2
      (TXB2) decreased after treatment with 4 IU/ml of INF-alpha but was augmented with
      150 and 300 IU/ml. The three doses used diminished the synthesis of 5
      hydroxyeicosatetraenoic acid (5-HETE) and increased the production of 12-HETE. We
      also studied the synthesis of uterine products of cyclooxygenase and lipoxygenase
      in uterine tissue from ovariectomized rats injected with 17 beta-estradiol and
      preincubated with IFN-alpha. We found that the three doses of IFN-alpha
      diminished the production of 6-keto-PGF1 alpha, PGE2, PGF2 alpha and TXB2 as well
      as 5-HETE and 12-HETE. These findings show that IFN-alpha modifies the basal
      synthesis of PGs from uterine tissue. Ovine and bovine trophoblastic protein
      prevents luteolysis by inhibiting the synthesis of PGF2 alpha. On the other hand,
      IFN-alpha shows 70% homology with ovine trophoblastic protein and binds to the
      same receptor. The results of the present study suggest that IFN-alpha may also
      act in the rat as a luteotrophic agent.

PMID- 8577781
TI  - Effects of dietary n-3, n-6 and n-9 polyunsaturated fatty acids on benzo(a)pyrene
      induced forestomach tumorigenesis in C57BL6J mice.
AB  - The modulating effect of dietary polyunsaturated fatty acids (PUFAs) on
      benzo(a)pyrene-induced forestomach tumorigenesis was assayed in mice fed with
      corn oil (CO), olein (O), Zizyphus mistol seed oil (MO), cod liver oil (CLO), and
      mixed fat (Stock diet). The fatty acid composition of liver lipids correlated
      well with the fatty acid composition of each diet. Only mice fed the O diet
      showed biochemical and clinical evidences of essential fatty acid deficiency
      (EFAD). Only 3 animals developed well-differentiated invading squamous cell
      carcinomas in the O group. The papilloma incidence was reduced in MO and CLO with
      respect to the O group. Forestomach papillomatosis was increased in mice fed an n
      9 enriched diet in comparison to stock and CO groups. In comparison with stock
      mice, the frequency of multiple epidermoidal hyperplasia (MEH) was significantly
      decreased in the CLO group. Animals fed n-3 enriched diets (MO and CLO) showed
      significant antipromoting effect. These findings indicate that dietary fat can
      modulate tumorigenesis initiated in mouse forestomach by benzo(a)pyrene. In
      addition, the lack of action of an n-6 fatty acid-enriched diet in our
      experimental model suggests that the effect of PUFAs on tumorigenesis has target
      tissue specificity. Mistol seed oil might be of potential value as a natural
      vegetable antipromoter nutrient.

PMID- 8577782
TI  - Diets rich in eicosapentaenoic acid and gamma-linolenic acid affect phospholipid
      fatty acid composition and production of prostaglandins E1, E2 and E3 in turbot
      (Scophthalmus maximus), a species deficient in delta 5 fatty acid desaturase.
AB  - Duplicate groups of juvenile turbot, (Scophthalmus maximus), were fed diets
      containing either Marinol K (MO), a marine fish oil rich in eicosapentaenoic acid
      (EPA; 20:5, n-3) or borage oil (BO), rich in gamma-linolenic acid (GLA; 18:3, n
      6), for a period of 12 weeks. Individual phospholipid fatty acid compositions
      from hearts of fish fed BO had significantly more 18:2, n-6, GLA, 20:2, n-6,
      dihomo-gamma-linolenic acid (DHGLA; 20:3, n-6) and total n-6 polyunsaturated
      fatty acids (PUFA), but significantly less arachidonic acid (AA; 20:4, n-6),
      compared to fish fed MO. In both phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE) from heart, the DHGLA was increased by over 50-fold
      in fish fed BO while AA was reduced by over two-thirds, compared to fish fed MO.
      In brain, EPA was the major C20 PUFA, i.e. potential eicosanoid precursor in all
      phospholipids from fish fed MO, with the EPA level being twice that of AA in
      brain phosphatidylinositol (PI). DHGLA was the major C20 PUFA in all phospholipid
      classes from fish fed BO. In kidney and gill, EPA was the predominant C20 PUFA in
      all phospholipid classes, except PI, in fish fed MO. In kidney of fish fed BO,
      DHGLA was the major C20 PUFA in all phospholipid classes, except PE. In gill of
      fish fed BO, DHGLA was the major C20 PUFA in all phospholipid classes, including
      PI, where DHGLA was over 2.5-fold greater than AA. In homogenates of heart,
      kidney and gill from BO-fed fish the prostaglandin E1 (PGE1) concentration was
      significantly increased compared to MO-fed fish. In heart and kidney homogenates
      from fish fed MO the PGE3 concentration was significantly increased compared to
      fish fed BO. The ratio of PGE2/PGE1 was significantly reduced in brain, heart,
      kidney and gill homogenates from fish fed BO compared to those fed MO.

PMID- 8577783
TI  - Cytotoxic action of cis-unsaturated fatty acids on human cervical carcinoma
      (HeLa) cells in vitro.
AB  - The effect of n-3 and n-6 fatty acids (FAs) on the growth of human cervical
      carcinoma (HeLa) cells was studied. Of all the FAs tested, docosahexaenoic acid
      (DHA, 22:6 n-3) and eicosapentaenoic acid (EPA, 20:5 n-3) were found to be the
      most potent in their cytotoxic action on HeLa cells and the potency of various
      fatty acids with regard to their cytotoxic action was as follows: DHA > EPA >
      dihomo-gamma-linolenic acid (DGLA) = gamma-linolenic acid (GLA) > linoleic acid
      (LA) > arachidonic acid (AA) > alpha-linolenic acid (ALA). The cycloxygenase
      inhibitor indomethacin, the lipoxygenase inhibitor nordihydroguaretic acid
      (NDGA), the antioxidants vitamin E, butylated hydroxyanisole (BHA), and butylated
      hydroxytoluene (BHT), the superoxide anion quencher superoxide dismutase (SOD),
      the hydroxyl and hydrogen peroxide quenchers mannitol and catalase, respectively,
      and the calmodulin antagonists trifluoperazine (TFP) and chlorpromazine (CPZ)
      could all block the cytotoxic action of GLA, which was used as a representative
      cytotoxic FA, on HeLa cells. On the other hand, copper and iron salts and
      buthionine sulfoxamine, a glutathione (GSH) depletor, potentiated the cytotoxic
      action of suboptimal doses of GLA. GLA-induced radical generation and lipid
      peroxidation in HeLa cells could be blocked by indomethacin, NDGA and calmodulin
      antagonists. The cytotoxic action of cis-unsaturated fatty acids (c-UFAs) is not
      dependent on the alteration in the protein kinase C levels since no alteration in
      the diacylglycerol levels was observed. Hydroxy and hydroperoxy products of GLA
      were found to be toxic to HeLa cells, whereas prostaglandin (PG)E1, PGF2 alpha,
      and prostacyclin stimulated cell growth. From these results, it is evident that
      radicals are the modulators of the cytotoxic action of c-UFAs, that their
      formation is a calmodulin-dependent process, and that lipoxygenase products may
      mediate the tumoricidal action of FAs.

PMID- 8577784
TI  - Analysis of anandamide, an endogenous cannabinoid substance, and of other natural
      N-acylethanolamines.
AB  - Recent reports have suggested that N-arachidonoylethanolamine (anandamide) acts
      as an endogenous ligand for cannabinoid receptors in mammalian brain. Here we
      describe methods for the extraction, purification and analysis of anandamide and
      related N-fatty acyl-ethanolamines (NAEs). Liquid-phase extraction, silica gel G
      column chromatography and thin-layer chromatography (TLC) were employed for
      sample fractionation. Three analytical high-performance liquid chromatography
      (HPLC) methods for purification of NAEs were developed. Finally, analyses of NAEs
      by gas chromatography/mass spectrometry (GC/MS) are described. The applications
      of these analytical methods to the identification of anandamide and related NAEs
      in cell cultures as well as of artifacts in biosynthetic studies are described.

PMID- 8577785
TI  - Metabolism of leukotrienes is impaired in hepatocytes from rats with
      thioacetamide-induced liver cirrhosis.
AB  - It is likely that the hepatocellular metabolism of potent mediators of
      inflammation is impaired in chronic liver injury. Therefore, in this study the
      degradation of the leukotrienes LTC4, LTE4 and LTB4 was investigated in isolated
      liver parenchymal cells (LPC) from rats with thioacetamide-induced macronodular
      liver cirrhosis or after bile duct ligation. The degradation of LTE4 as well as
      the formation of N-acetyl-LTE4 was significantly delayed in LPC from macronodular
      cirrhotic rats but not in those from bile duct-ligated rats. LPC from
      macronodular cirrhotic rats eliminated LTC4 at the same rate as isolated
      hepatocytes from control animals. The rate of LTB4 degradation was significantly
      decreased by 35% in LPC from macronodular cirrhotic rats. Furthermore, the rate
      of LTB4 hydroxylation was significantly lower by 50% in microsomes isolated from
      hepatocytes of macronodular cirrhotic rats than in those from controls. In
      summary, one may conclude that the N-acetylation reaction of LTE4 and the
      hydroxylation reaction of LTB4 is impaired in LPC from rats with thioacetamide
      induced macronodular cirrhosis.

PMID- 8577786
TI  - Antagonism of isoniazid-induced convulsions by abecarnil in mice tolerant to
      diazepam.
AB  - The ability of the benzodiazepine receptor full agonist diazepam, the selective
      agonist abecarnil, and the partial agonist imidazenil to antagonize convulsions
      induced by isoniazid (200 mg/kg, S.C.) was studied in mice chronically treated
      with diazepam (3 mg/kg, i.p., three times daily) or abecarnil (0.1 or 1 mg/kg,
      i.p., three times daily or 6 mg/kg, S.C., daily). Diazepam induced tolerance to
      its own anticonvulsant effect. In contrast, chronic treatment with abecarnil
      failed to induce tolerance to its own anticonvulsant activity. Animals treated
      with abecarnil at 0.1 mg/kg developed cross-tolerance to imidazenil, whereas
      those treated with 1 mg/kg became less sensitive to diazepam. Mice chronically
      treated with abecarnil at 6 mg/kg showed almost complete tolerance to diazepam.
      Abecarnil was able to antagonize the convulsions elicited by isoniazid in
      diazepam-tolerant mice. These data indicate that chronic administration of
      abecarnil, unlike that of classical benzodiazepines, does not induce tolerance to
      its anticonvulsant effect, and that abecarnil overcomes tolerance induced by long
      term treatment with the full agonist diazepam.

PMID- 8577787
TI  - The 5-HT4 receptor antagonist, GR113808, reduces ethanol intake in alcohol
      preferring rats.
AB  - The present study evaluated the effect of the selective 5-HT4 receptor
      antagonist, GR113808, on ethanol intake in alcohol-preferring rats. Rats were
      offered 10% ethanol 2 h/day. In the first experiment, rats had food and water ad
      lib and 10% ethanol was offered from 1800 to 2000 h. In the second experiment,
      food was freely available, 10% ethanol was offered 2 h/day, from 1800 to 2000 h,
      and water was offered for 4 h, from 1800 to 2200 h. In both experiments GR113808
      was subcutaneously injected at doses of 1, 3, or 10 mg/kg for 4 consecutive days,
      5 min before access to ethanol. From the first day of administration, GR113808
      significantly reduced the volitional ethanol intake in water sated rats at the
      three doses tested. In water-deprived rats, it reduced ethanol intake at 3 and 10
      mg/kg, without modifying total fluid and food intake. In both experiments the
      effect of GR113808 remained rather stable during the 4 days of administration.
      The present findings, showing that the 5-HT4 receptor antagonist, GR113808,
      selectively reduces ethanol intake in alcohol-preferring rats, suggest that 5-HT4
      receptors may play a role in alcohol intake control.

PMID- 8577788
TI  - Tail pinch increases acetylcholine release in rat striatum even after toluene
      exposure.
AB  - The effect of tail pinch on acetylcholine release in the striatum of freely
      moving rats was studied by microdialysis immediately after inhalation exposure to
      toluene (2000 ppm, 2 h) or exposure to air only. It has recently been found that
      toluene increases extracellular dopamine levels while decreasing acetylcholine
      release, and that dopamine uptake inhibition increases both extracellular
      dopamine levels and acetylcholine release, suggesting that toluene decreases
      acetylcholine release by a dopamine-independent mechanism. The present experiment
      was an attempt to study if a behaviourally induced increase of extracellular
      dopamine differs from that induced by toluene in affecting striatal acetylcholine
      release. Acetylcholine released increased during tailpinch in the unexposed as
      well as the toluene exposed group. No difference between the two groups in the
      acetylcholine release response to tailpinch was demonstrated. The result supports
      the conclusion that acute toluene exposure decreases acetylcholine release via a
      dopamine independent mechanism, and suggests that toluene exposure does not
      affect the striatal acetylcholine response to an acute stressful stimulus.

PMID- 8577789
TI  - Effects of SCH39166 and domperidone on the meal patterning of male rats.
AB  - In male rats given free access to food (45 mg pellets) and water, ingestive
      behavior is structured into meals. The selective dopamine D1 antagonist SCH39166
      had little effect on total food intake, meal size, or feeding rate. However, it
      did produce a marked, dose-related reduction in drinking that resulted from an
      increase in intermeal interval with unchanged meal size. Possible peripheral and
      central explanations of this effect are discussed. In a second experiment, the
      peripheral dopamine D2 antagonist, domperidone, was shown to have little effect
      on either feeding or drinking. A dose of 10 mg/kg did reduce feeding rate, but
      this probably represents a central effect, because doses that were only slightly
      higher have previously been shown to reduce stimulant-induced hyperactivity and
      stereotypy. These experiments confirm the functional distinction between D1-like
      and D2-like dopamine receptors in the control of ingestive behavior, with the D1
      receptor having a greater role in drinking and central D2 receptors affecting
      several aspects of feeding behavior.

PMID- 8577790
TI  - Isradipine inhibits nicotine intravenous self-administration in drug-naive mice.
AB  - The effect of isradipine, a dihydropyridine calcium antagonist, on intravenous
      self-administration of nicotine in naive mice has been investigated. When
      nicotine injections were made contingent upon nose-poke response by naive mice,
      they increased their rate of nose poking with respect to animals receiving
      contingent saline injections or yoked control animals receiving noncontingent
      nicotine injections. Pretreatment of mice with mecamylamine (2.4 mg/kg) inhibited
      self-administration of nicotine contingent upon a nose-poke response. The same
      effect was observed with isradipine (0.5-1.0 mg/kg) in a dose-related manner and
      stereospecifically. These data suggest that isradipine suppresses the reinforcing
      properties of nicotine and might be useful for treatment of nicotine abuse.

PMID- 8577791
TI  - 7-OH-DPAT injected into the accumbens reduces locomotion and sucrose ingestion:
      D3 autoreceptor-mediated effects?
AB  - 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) injected bilaterally in the
      nucleus accumbens (NAC) resulted in profound, noncatatonic, dose-dependent (0.3-3
      mg total dose) hypolocomotion but without inducing yawning. It also decreased
      intake of a highly preferred 3% sucrose solution (1 microgram total dose).
      Systemic injection of 7-OH-DPAT (0.1-3.0 mg/kg, i.p.) similarly induced
      hypolocomotion while failing to induce yawning. In none of these studies did rats
      show any signs of hyperlocomotion or any stereotyped responses normally
      associated with D2 or mixed D1/D2 receptor stimulation. These data suggest that
      hypolocomotion elicited by 7-OH-DPAT in the NAC may be mediated at the D3
      receptor as distinct from the D2 dopamine receptor. We discuss the possibility
      that the behavioural effects we observed are mediated at D3 autoreceptors.

PMID- 8577792
TI  - Effect of threonine on the behavioural development of the rat.
AB  - Rats received different levels of threonine (Thr), one, 1.7 and four times the
      normal dietary intake, from conception to adulthood. The mothers were fed the
      experimental diets before and during pregnancy. Their offspring received a daily
      oral load of Thr or placebo until weaning. Thereafter, the juveniles were fed the
      same diet as their mothers. Morphologic development, ingestive behaviour, homing,
      and locomotion were observed before weaning. Exploration and spontaneous
      alternation were studied thereafter. Animals exposed during gestation to 1.7
      times the normal Thr intake consumed more food during the test of independent
      ingestion. Grooming showed inconsistent variations between days 12 and 29 in pups
      fed 1.7 times the normal Thr intake. Rats performed equally well on the other
      behavioural tasks independently of the dietary treatment. We conclude that Thr
      intake as much as four times higher than the levels found in normal diets does
      not impair the behavioural ontogenesis of the rat.

PMID- 8577793
TI  - Age-dependent anticonvulsant action of clonazepam in the N-methyl-D-aspartate
      model of seizures.
AB  - Seizures may result from an impaired balance between excitation and inhibition.
      We tested whether clonazepam [a benzodiazepine that enhances GABAA inhibitory
      transmission (0.2 or 1.0 mg/kg, intraperitoneally [i.p.])] suppresses an age
      dependent pattern of N-methyl-D-aspartate (NMDA)-induced phenomena in 7-, 12-, 18
      , 25-, and 60-day-old rats (10, 40, 100, 100, and 200 mg/kg of NMDA, i.p.,
      respectively). There were no effects of clonazepam against the NMDA-induced
      automatisms and emprosthotonus. In 7-day-old rats, clonazepam was proconvulsant
      in clonic-tonic seizures (it decreased the latency to onset of seizures, whereas
      it was anticonvulsant in 25-day-old rats. There was no difference between
      anticonvulsant effects of clonazepam and its solvent in 12- and 60-day-old rats.
      Both cortical and hippocampal EEG seizures was extremely poor in this model.
      There was no improvement of EEG recording after clonazepam. The results
      demonstrate that impaired excitation cannot be simply balanced by an enhanced
      inhibition and that the drug effects in young animals cannot be predicted from
      the effects in adults.

PMID- 8577794
TI  - Factor analysis of spatiotemporal and ethological measures in the murine elevated
      plus-maze test of anxiety.
AB  - Recent research employing the elevated plus-maze to assess anxiety in rodents has
      incorporated a variety of behavioral elements in addition to the standard
      parameters of entries onto and time spent in the aversive open arms. In the
      present study, we have used a large database comprising the behavioral profiles
      of 90 undrugged mice to examine the relationship between the standard
      spatiotemporal measures and a range of specific behaviors related to the
      defensive repertoire of the mouse. A factor analysis applied to the standard
      measures revealed two factors related to anxiety and locomotor activity. The
      simple addition of center time (an infrequently recorded measure) to the analysis
      yielded a third factor, most probably related to decision making. A large-scale
      factor analysis applied to all measures further confirmed the existence of
      factors related to anxiety, locomotor activity, and decision making, and revealed
      three further factors thought to represent risk assessment, vertical activity,
      and exploratory behavior. Thus, the inclusion of ethological measures not only
      confirmed prior knowledge based on a very limited range of measures, but also
      demonstrated the existence of additional behavioral dimensions. The potential
      applications of this knowledge are discussed.

PMID- 8577795
TI  - Sleep and waking in 5,7-DHT-lesioned or (-)-pindolol-pretreated rats after
      administration of buspirone, ipsapirone, or gepirone.
AB  - The effects of partial 5-HT1A receptor agonists buspirone (0.010-4.0 mg/kg),
      ipsapirone (0.010-6.0 mg/kg), and gepirone (0.025-4.0 mg/kg) on sleep and waking
      were studied in vehicle-treated and 5,7-dihydroxytryptamine (5,7-DHT)-injected
      rats. 5,7-DHT-treated animals showed a marked and significant serotonin and 5
      HIAA depletion in the raphe regions of the pons and upper brain stem, cerebral
      cortex, hippocampus, and striatum. Subcutaneous administration of the partial
      agonists to both the vehicle-infused and the 5,7-DHT-treated animals
      significantly increased waking (W) and reduced light sleep (LS), slow-wave sleep
      (SWS), and REM sleep (REMS). Pretreatment with (-)pindolol (2.0 mg/kg) reversed
      the effects of buspirone and gepirone on W and non-REM sleep (LS + SWS) whereas
      REMS remained suppressed. (-)-Pindolol failed to reverse the effects of
      ipsapirone on sleep and W. The present results tend to indicate that increased W
      after acute administration of buspirone, ipsapirone, or gepirone depends upon the
      activation of postsynaptic 5-HT1A receptors. The well-known anxiolytic action
      observed after chronic administration of the azapirones seems to be related to
      mechanisms other that these involved in their stimulant effect.

PMID- 8577796
TI  - Mood and performance effects of caffeine in relation to acute and chronic
      caffeine deprivation.
AB  - The mood and performance effects of caffeine deprivation (either 90 min,
      overnight, or at least 7 days) and ingestion (70 and 250 mg) were compared in
      young adults who were normally either moderate consumers (n = 49) or nonconsumers
      of caffeine (n = 18). Overnight caffeine deprivation produced dysphoric symptoms
      characteristic of caffeine withdrawal that were reduced, but still present, after
      longer-term abstinence. Acute caffeine intake affected the withdrawn consumers,
      nonwithdrawn consumers, and nonconsumers similarly. It increased jitteriness and
      decrease tiredness and headache. Furthermore, hand steadiness decreased as
      caffeine dose increased, whereas 70 mg, but not 250 mg, of caffeine was found to
      enhance performance on a simple reaction time task. These findings support the
      view that the negative effects experienced after overnight and longer-term
      caffeine deprivation play a significant role in influencing consumption of
      caffeine-containing drinks. Therefore, it would appear that to avoid the
      dysphoric symptoms resulting from both under- and overconsumption, regular
      caffeine consumers would have to regulate their caffeine intake fairly precisely.

PMID- 8577797
TI  - Blockade of lithium chloride-induced conditioned place aversion as a test for
      antiemetic agents: comparison of metoclopramide with combined extracts of
      Zingiber officinale and Ginkgo biloba.
AB  - The present study tests the hypothesis that the blockade of lithium chloride
      induced conditioned place aversion might be a suitable model to assess antiemetic
      properties of drugs, especially in species that do not vomit, like rats. The
      effects of the known antiemetic compound metoclopramide were compared with those
      of zingicomb, a combination preparation of extracts of Ginkgo biloba and Zingiber
      officinale, also presumed to have antiemetic properties. Place conditioning was
      performed using a conventional three-compartment test procedure. On three
      successive conditioning trials, rats received an intraperitoneal (i.p.) injection
      of lithium chloride (125 mg/kg) and were placed into the compartment that they
      had preferred over three baseline trials. During the test, rats treated with
      lithium chloride (LiCl) spent less time in the treatment compartment, indicative
      of a conditioned place aversion (CPA). In the first experiment, metoclopramide
      (MCP) was administered intragastrically (IG) in doses of 2 or 10 mg/kg 60 min
      prior to LiCl injection. The pretreatment with 50 and 100 mg/kg zingicomb
      attenuated the LiCl-produced CPA, whereas a dosage of 10 mg/kg had no effect.
      These findings suggest that LiCl-induced CPA is a viable procedure with which to
      assess the antiemetic properties of metoclopramide. Furthermore, the data confirm
      the hypothesis that the phytopharmacon zingicomb might have antiemetic properties
      that are comparable to those of metoclopramide.

PMID- 8577798
TI  - Effects of valproate and lorazepam on experimental anxiety: tolerance,
      withdrawal, and role of clonidine.
AB  - The anxiolytic-like effects tolerance and withdrawal from chronic treatment with
      sodium valproate [200, 300, and 400 mg/kg, intraperitoneally (i.p.)] were
      compared with those of a known anxiolytic drug, lorazepam (0.025, 0.05, and 0.10
      mg/kg, i.p.), in the light-dark aversion test in mice. Furthermore, we
      investigated whether acute treatment with clonidine, 0.03 mg/kg i.p., an alpha 2
      adrenoceptor agonist, could reduce the increased anxiety on withdrawal from
      chronic treatment. Mice were given 14 daily i.p. injections of valproate,
      lorazepam, or vehicle and were tested in the light-dark aversion test 30 min or
      24 or 48 h after the last drug or vehicle administration. Results showed that
      both acute and chronic valproate treatment reduced the aversion of mice for the
      light area, as well as increased the number of transitions, thus indicating an
      anxiolytic-like potential. Furthermore, in contrast to lorazepam, tolerance to
      the anxiolytic-like effects of valproate did not occur, and withdrawal from
      chronic treatment (300 mg/kg, i.p.) in our behavioral paradigm was not associated
      with any behavioral disturbances referring to an increased anxiety state.
      Finally, low doses of clonidine (0.03 mg/kg, i.p.) were shown to have anxiolytic
      properties and to reverse the anxiogenic effects of lorazepam on withdrawal.

PMID- 8577799
TI  - Behavioral sensitization, behavioral tolerance, and increased [3H]WIN 35,428
      binding in rabbit caudate nucleus after repeated injections of cocaine.
AB  - This study examined whether changes in the behavioral response to repeated
      intravenous injections of cocaine hydrochloride (4 mg/kg, twice daily for 22
      days) might be related to alterations in the dopamine (DA) transporter as
      measured by the binding of the potent cocaine analog [3H]WIN 35,428 to membranes
      derived from fresh caudate tissue. Rabbits demonstrated both tolerance and
      sensitization. Tolerance occurred for cocaine elicited convulsions, whereas
      sensitization occurred to the ability of cocaine to elicit motor activity, facial
      twitches, and head bobbing. Cocaine-exposed animals demonstrated a significant
      17% increase in the Bmax of specific [3H]WIN 35,428 binding to caudate membranes
      with no change in Kd. The increase in Bmax was observed at 42 but not 96 h after
      the last chronic cocaine administration. There was no change in [3H]WIN 35,428
      binding at 42 h after a single injection of cocaine. We suggest that the
      upregulation of the dopamine transporter in the caudate nucleus reflected the
      mechanisms involved in tolerance rather than sensitization.

PMID- 8577800
TI  - Effect of fluoxetine on learning and memory involves multiple 5-HT systems.
AB  - Diverse evidence suggests that 5-HT uptake blockers enhance learning and memory.
      However, there is no information about the mechanisms of action involved in such
      effects. The aim of the present work was to investigate the nature of the
      receptors involved in the effects of fluoxetine on learning. Therefore, a dose
      response curve of posttraining injection (intraperitoneal) of fluoxetine was
      carried out in an associative learning task (auto-shaping). Fluoxetine or the
      vehicle was injected 10 min after 5-HT antagonists: (+/-)-pindolol, (+/-)
      propanolol, NAN-190, ketanserin, ritanserin, mesulergine, MDL 72222, or SDZ 205
      557. Presynaptic activity was eliminated by means of chloroamphetamine
      pretreatment. Scopolamine (an anticholinergic) and dizocilpine (a noncompetitive
      NMDA receptor antagonist) were also used. Results showed that fluoxetine enhanced
      learning of the conditioned response (CR) in a dose-dependent fashion. All 5-HT
      antagonists had no effects by themselves but inhibited the effects of fluoxetine
      at different degrees. Decrement of CR produced by scopolamine was reversed by
      fluoxetine. Dizocilpine did not affect CR but prevented the effects of
      fluoxetine. The present findings suggest that the actions of fluoxetine on
      learning are due to an interaction with multiple receptors of postsynaptic
      nature.

PMID- 8577801
TI  - Paradoxical conditioning of the plasma copper and corticosterone responses to
      bacterial endotoxin.
AB  - The cascade of physiologic mechanisms in response to infection, the acute phase
      response, is recognized as having a major role in host defense. Two such
      responses are an increase in plasma copper and activation of the hypothalamic
      pituitary-adrenal axis, which are consistently reported to occur during bacterial
      infection. We aimed to determine whether the alterations in plasma copper and
      corticosterone were conditionable using the conditioned taste aversion paradigm.
      The regime involved the pairing of a novel-tasting saccharine solution (the
      conditioned stimulus) with lipopolysaccharide (the unconditioned stimulus). Seven
      days after the initial pairing of these stimuli (the test day), the saccharine
      solution was represented. Animals exposed to this condition displayed a
      significant decrease in plasma copper levels. In addition, these rats experienced
      a reduction in plasma corticosterone that was time dependent. Paradoxically, the
      conditioned response of both these variables were in a direction contrary to that
      reported during bacterial infection. These results suggest that some acute phase
      responses may condition as a rebound response, or in an opposing trend to that
      occurring as the initial reaction.

PMID- 8577802
TI  - Alteration of antioxidant status in diabetic rats by chronic exposure to
      psychological stressors.
AB  - Antioxidant status was measured in heart, liver, kidney, lung, and erythrocytes
      of 2-week streptozotocin-diabetic male Wistar rats exposed to chronic
      intermittent psychological stress consisting of 1 h of restraint twice daily for
      14 days. Diabetes reduced erythrocyte and heart and liver susceptibility to
      hydrogen peroxide-induced glutathione depletion. Susceptibility to peroxide
      induced thiobarbituric acid reactive substance (TBARS) formation increased in
      erythrocytes, liver, kidney, and lung but decreased in heart. Significant changes
      also occurred in glutathione levels (increased in heart and decreased in liver)
      and in the activities of catalase (reduced in liver and kidney), glutathione
      reductase (elevated in heart and liver), and glutathione peroxidase (decreased in
      liver and lung), but not Cu,Zn-superoxide dismutase. Stress potentiated diabetes
      associated hyperglycemia and attenuated diabetes-induced hyperlipidemia. In
      addition, the reduction in peroxide-induced glutathione depletion in heart and
      liver and the increased TBARS formation in kidney and lung were reversed.
      Similarly, the diabetes-induced induced increase in liver glutathione reductase
      and decreases in liver and lung glutathione peroxidase activities were abolished
      by stress. Thus, the relative resistance of antioxidant systems to stress can be
      modified under pathologic conditions in which antioxidant alterations are
      present.

PMID- 8577803
TI  - Play behavior and stress responsivity in periadolescent offspring exposed
      prenatally to cocaine.
AB  - Play behavior and stress responsiveness were examined in offspring exposed
      gestationally to cocaine. The subjects were offspring of Sprague-Dawley rat dams
      given s.c. injections of 40 mg/kg/3 cc cocaine HC1 daily from gestational days 8
      20 (C40), pair-fed dams injected daily with saline (PF), and untreated control
      dams (LC). Periadolescent (postnatal day (P) 30-36) male and female rats were
      assigned to either pretest Stress or No Stress conditions. Every other day Stress
      animals were exposed to a stressor (on P30--foot shock; P32--white noise; P34-
      forced swim; P36--foot shock), with each stressor being administered 4 h prior to
      a play session. Immobility during one of the stressors, foot shock, was used to
      assess stress responsiveness. Play sessions consisted of pairing each
      experimental animal with a same-sex, nonexperimentally manipulated conspecific
      for 7 min. The results indicated that periadolescent offspring exposed
      gestationally to cocaine differed from controls in their stress responsivity, as
      evidenced by a failure to show increased immobility during the final foot shock
      session. Also, while cocaine-exposed juveniles did not differ from controls in
      their own play behavior, these offspring elicited less play solicitation from
      conspecifics, as evidenced by an increased latency to be pounced, and decreased
      frequency and duration of being pounced. These findings parallel earlier evidence
      for altered stress responsiveness in adult cocaine-exposed rats and also suggest
      that prenatal exposure to cocaine results in altered social cues.

PMID- 8577804
TI  - Influence of acute exposure to heat on the blood-brain barrier permeability
      during acute hypertension.
AB  - In mild hyperthermic rats with acute hypertension induced by intravenous
      injection of adrenaline, changes in blood-brain barrier permeability to
      macromolecules were investigated using Evans blue as indicator. Evans blue
      albumin extravasation was determined macroscopically, and a quantitative
      estimation with spectrophotometer using homogenized brain to release the dye was
      also performed to evaluate the macroscopic findings. Four groups of rats were
      studied: group I: control normothermia; group II: acute exposure to heat; group
      III: normothermia + acute hypertension; group IV: acute exposure to heat + acute
      hypertension. The rats were anesthetized with diethyl-ether. Body temperature was
      increased by elevating ambient temperature in the vented box covered with a 3 mm
      thick black copper plate. The colonic temperature was increased to 39 +/- 0.5
      degrees C. During adrenaline-induced acute hypertension the mean arterial blood
      pressure increased in both normothermic and mild hyperthermic animals. Mean
      values for Evans blue dye were found to be 0.20 +/- 0.04 mg% whole brain in
      normothermic control rats and 0.30 +/- 0.1 mg% in hyperthermic rats (p < 0.05).
      Mean values for Evans blue dye in the whole brain were found to be 0.63 +/- 0. 2
      mg% in the normothermic rats and 0.40 +/- 0.2 mg% in the mild hyperthermic rats
      during adrenaline-induced hypertension (p < 0.05). Our results show that the
      extravasation of Evans blue albumin was less pronounced in the brains of mild
      hyperthermic rats compared to normothermic rats after adrenaline-induced acute
      hypertension.

PMID- 8577805
TI  - 5-HT1A and 5-HT2 receptors mediate hypo- and hyperthermic effects of tryptophan
      in pargyline-pretreated rats.
AB  - Mechanisms of tryptophan (a 5-HT precursor)-induced changes in body temperature
      were investigated in rats pretreated with pargyline, a monoamine oxidase
      inhibitor (MAO-I). Tryptophan (100 mg/kg, i.p.) did not affect the body
      temperature in rats, but it produced significant hypothermia followed by marked
      hyperthermia and higher mortality in the pargyline-pretreated rats. 5-HT
      depletion with p-chlorophenylalanine (p-CPA, 100 mg/kg/day for 3 days)
      significantly suppressed not only the body temperature change but also the
      mortality and 5-HT syndrome following tryptophan plus pargyline administration.
      Although propranolol (10 mg/kg, i.p.), a beta-adrenoceptor antagonist, did not
      alter the hypothermia caused by tryptophan in the pargyline-pretreated rats,
      pindolol (2 mg/kg, S.C.), a 5-HT1A receptor and beta-adrenoceptor antagonist,
      suppressed the hypothermia but not the hyperthermia or mortality caused by the
      same treatment. On the other hand, spiperone and ketanserin, 5-HT2 receptor
      antagonists, at doses of 3 mg/kg, potentiated the hypothermia and completely
      suppressed the hyperthermia and mortality caused by tryptophan in the pargyline
      pretreated rats. These results suggest that tryptophan-induced hypo- and
      hyperthermia are mediated by 5-HT1A and 5-HT2 receptors, respectively, in the
      pargyline-pretreated pretreated rats.

PMID- 8577806
TI  - Cycloheximide inhibits context memory and long-term habituation in the crab
      Chasmagnathus.
AB  - A shadow moving over head elicits an escape response in the crab Chasmagnathus
      that habituates promptly and for a long period. The effect of the protein
      synthesis inhibitor cycloheximide (CY) on this long-term memory was analyzed. Two
      hours after injection, 10 micrograms CY inhibited [14C]-amino amino acid
      incorporation into cerebral plus thoracic ganglia by 88% and 20 micrograms by
      92%, but no inhibition was found at 24 h. A single injection of 10-20 micrograms
      CY given 30 min before training, failed to affect the short-term habituation.
      Similar doses impaired both context memory (CM) and long-term habituation (LTH)
      when tested at 72 and 120 h but only CM at 24 h. Such a disparity was explained
      by an unspecific depressing effect upon the response, attributed to an
      interaction between CY and training. The hypothesis was confirmed, because CY
      injected immediately after training disclosed amnestic effect at 24 h on both CM
      and LTH. A similar effect was proven when animals were injected at 2 h but not at
      6 h after training. Results from experiments with pretraining and pretesting
      injections put aside a state-dependence or retrieval deficit effects of the drug.
      Taken together, findings of this article argue strongly for de novo protein
      synthesis as a mechanism of LTH and for the close relation between CM and LTH.

PMID- 8577807
TI  - Effects of acute and chronic morphine on rotational behavior in nigral-lesioned
      rats.
AB  - Stimulation of mu-opioid receptors located on dopaminergic neurons in the
      striatum and the nucleus accumbens increases dopamine release, which may account
      for some of the behavioral effects of morphine. In this study, we examined the
      effects of acute and chronic morphine treatment on rotational behavior in rats
      with unilateral 6-hydroxydopamine dopamine (6-OHDA)-induced lesions of the
      nigrostriatal pathway. Rats receiving morphine acutely (0.3-10 mg/kg) did not
      show a significant bias toward contralateral or ipsilateral turning. Mini osmotic
      pumps dispensing morphine continuously (20-24 mg/kg/day) were implanted s.c. in
      these animals. This treatment induced tolerance to the behavioral depression
      produced by the highest dose of morphine (10 mg/kg) when it was given acutely. A
      slight but significant increase in ipsilateral turning occurred over the range of
      morphine doses examined. The effects of morphine on rotational behavior are
      slight, and do not correlate well with the reported increase in locomotor
      activity or extraneural dopamine in the striatum that are produced by doses of
      morphine similar to the ones tested in this study.

PMID- 8577808
TI  - Reward and reinforcement produced by drinking sucrose: two processes that may
      depend on different neurotransmitters.
AB  - The capacity of sucrose drinking to produce conditioned place preference (CPP)
      and the effects of dopamine and opioid receptor blockade on acquisition of this
      preference and on sucrose consumption were evaluated. The establishment of place
      preference would reflect the reinforcing consequences of drinking, while the
      amount of sucrose solution consumed would illustrate its rewarding properties.
      Male Wistar rats were allowed to drink an 18% sucrose solution. No deprivation
      was used. Drinking produced place preference, and this was blocked with cis(z)
      flupentixol, 0.5 mg/kg. Naloxone, 16 mg/kg, not only blocked place preference,
      but also reduced sucrose consumption. In fact, animals consumed amounts similar
      to those consumed by rats given plain water. Lower doses of naloxone, 1 and 4
      mg/kg, also decreased sucrose consumption, but 1 mg/kg did not block place
      preference. As the dopamine antagonist did not affect consumption at a dose that
      inhibited conditioned place preference, it is suggested that dopamine is critical
      for the establishment of reinforcement produced by sucrose. Opioids seem to be
      more important for the rewarding effect because naloxone reduces drinking even at
      a dose that does not affect place preference.

PMID- 8577809
TI  - Intrauterine exposure to cocaine produces a modality-specific acceleration of
      classical conditioning in adult rabbits.
AB  - Previous studies had demonstrated that in utero exposure to cocaine produces
      structural changes in the development of the rabbit's anterior cingulate cortex.
      Because the anterior cingulate cortex has been proposed to subserve a variety of
      cognitive processes including associative learning, we investigated the effects
      of intrauterine exposure to cocaine on the acquisition of the rabbit's
      classically conditioned nictitating membrane response. Adult, sexually mature
      rabbits born of dams that had received intravenous injections of either saline or
      cocaine (4 mg/kg, twice a day) from day 8 to day 29 of gestation were classically
      conditioned by pairing tone and light CSs with an airpuff US. Rabbits that had
      been exposed to cocaine in utero demonstrated a more rapid acquisition of CRs to
      a tone CS but not to a light CS as compared with saline controls. Control
      experiments indicated that the accelerated learning to the tone CS was not due to
      sensitization, pseudoconditioning, altered baseline rate of responding, an
      increased responsiveness to the airpuff US, or to a change in the intensity
      threshold of the tone CS for elicitation of CRs. We conclude that in utero
      exposure to cocaine alters the processing of auditory stimuli and this leads to
      an abnormally rapid acquisition of CRs. It is suggested that this functional
      consequence of prenatal exposure to cocaine is due to structural abnormalities in
      anterior cingulate cortex.

PMID- 8577810
TI  - Hypothermic effect of harmala alkaloid in rats: involvement of serotonergic
      mechanism.
AB  - The effect of total alkaloid extracted from Peganum harmala seeds collected in
      Egypt on body temperature was studied in rats. Intraperitoneal administration of
      the Peganum harmala extract produced significant and dose-dependent hypothermia.
      Similarly, harmine and harmaline, major constituents of the harmala alkaloid,
      lowered the body temperature. Pretreatment with p-chlorophenylalanine (100
      mg/kg/day for 3 days), a 5-HT synthesis inhibitor, significantly attenuated the
      hypothermic effect of the total alkaloid and harmine, while it tended to block
      the hypothermic action of harmaline. Methysergide (2 mg/kg), a 5-HT antagonist,
      significantly attenuated the hypothermia induced by harmala alkaloids. Pindolol
      (0.05-2 mg/kg), a 5-HT1A receptor and beta-adrenoceptor antagonist, partly
      blocked the hypothermic effect of the harmala alkaloids in a dose-dependent
      manner, whereas propranolol (10 mg/kg), a beta-adrenoceptor antagonist, failed to
      alter it, suggesting that beta-adrenoceptor is not involved in the hypothermia
      caused by the alkaloids. Pretreatment with a dopamine receptor antagonist
      haloperidol (5 mg/kg, s.c. and 2 mg/kg, i.p. 24 and 2 h before the experiment,
      respectively) significantly attenuated the hypothermic effect of harmala
      alkaloids. Moreover, in haloperidol pretreated rats, methysergide (2 mg/kg, i.p.)
      and pindolol (0.05 and 2 mg/kg) completely attenuated the hypothermic effect of
      the alkaloids. These data suggest that harmala alkaloids produce hypothermic
      effect mainly through endogenous 5-HT stimulation of 5-HT1A receptor.

PMID- 8577811
TI  - Crude saponin extracted from Vietnamese ginseng and its major constituent
      majonoside-R2 attenuate the psychological stress- and foot-shock stress-induced
      antinociception in mice.
AB  - Effects of Vietnamese ginseng (VG) crude saponin and majonoside-R2, a major
      saponin constituent, on the psychological stress- and foot shock stress-induced
      antinociception in the tail pinch test were examined in mice. VG crude saponin
      (6.2, 12.5, and 25 mg/kg, P.O.) attenuated psychological stress- but not foot
      shock stress-induced antinociceptive response, whereas majonoside-R2 (3, 6.2, and
      12.5 mg/kg, P.O. and i.p.), as well as naloxone (2 mg/kg, i.p.), suppressed both
      psychological stress- and foot shock stress-induced antinociception. Pretreatment
      with the crude saponin (12.5 mg/kg, P.O.) or majonoside-R2 (6.2 mg/kg, P.O.) for
      5 days followed by the treatment in combination with stress for next 5 days did
      not affect the development of adaptation to foot shock stress, but they
      significantly suppressed the antinociceptive action of the stress measured on the
      first, second, and third day during the stress exposure period. Majonoside-R2
      (6.2 mg/kg, P.O.) but not the crude saponin (12.5 mg/kg, P.O.) significantly
      blocked the development of adaptation to psychological stress. These results
      suggest that VG crude saponin has the suppressing effect on psychological stress-
      and foot shock stress-induced antinociception and that majonoside-R2 is important
      for the action of the saponin.

PMID- 8577812
TI  - Impaired acquisition and operant responding after neonatal dopamine depletion in
      rats.
AB  - The effect of neonatal dopamine depletion in rats was examined using operant
      conditioning. Rat pups were given 6-hydroxydopamine (6-OHDA) or sham lesions at 3
      days of age. When tested as adults, 6-OHDA treated subjects were impaired in the
      acquisition of lever pressing for reward and displayed stereotyped sniffing
      patterns not observed in the control subjects. In addition, significantly lower
      rates of responding were measured for the lesion group during continuous
      reinforcement (CRF), dilution of reinforcer efficacy, and with progressively
      increasing fixed ratio requirements. Alpha-methyl-p-tyrosine (AMPT), given before
      one CRF session, attenuated responding in over half the lesion animals and in
      none of the controls. Dopamine content in caudate nucleus was found to
      significantly correlate with number of trials to acquisition and rates of
      responding following AMPT in the lesion group, but not in the control group.
      Overall, the results of this experiment showed that neonatal dopamine depletion
      does not lead to severe motor impairment or the inability to learn, but does
      disrupt the normal patterns of behavior associated with operant conditioning.

PMID- 8577813
TI  - Regulation of tyrosine protein kinase receptor Trk-B and motor function in rats
      following cardiac arrest.
AB  - Following 10 min cardiac arrest and resuscitation, male Sprague-Dawley rats
      developed posthypoxic myoclonus. Sixty days later, the motor function of the
      animals was restored. In the present study, we investigated brain levels of
      tyrosine protein kinase receptor Trk-B with quantitative immunoblot analysis at
      various time points following cardiac arrest. In the frontal cortex, a
      significant reduction of Trk-B was found in rats 3 days (53%) after cardiac
      arrest, whereas significant increases were detected in rats 14 (124%) and an
      average 60 days (98%) after cardiac arrest. In the striatum, significant
      increases were found in rats 3 (389%), 14 (483%), and 60 days (521%) after
      resuscitation. In contrast, significant reductions of Trk-B were detected in the
      cerebellum of rats 3 (46%), 14 (22%), and 60 days (18%) after cardiac arrest. The
      results indicate that regulation of Trk-B may vary in different brain regions and
      have important roles in recovery processes following hypoxic-ischemic insults to
      the brain.

PMID- 8577814
TI  - Triazolam in Alzheimer's disease: pilot study on sleep and memory effects.
AB  - We examined the effects on sleep and memory of a nighttime dose of triazolam,
      0.125 mg, in seven subjects with Alzheimer's disease (AD) who were reported by
      caregivers to be frequently up at night. Subjects were admitted to an
      intermediate care hospital ward for the 8-day ABA design protocol (placebo
      baseline-drug-placebo washout). Drug or placebo was given each evening at 2100 h.
      Sleep was assessed with a wrist-worn activity monitor. Memory was evaluated using
      a computerized delayed-matching-to-sample (DMTS) task administered at 0800 and
      2130 h. Triazolam had no significant effects on total sleep time at night,
      latency to sleep onset, number of arousals, or time asleep during the day. DMTS
      performance was significantly worse at night compared to morning during baseline,
      but there were no significant drug effects. Our results suggest the standard
      geriatric dose of triazolam, 0.125 mg, may not be an effective hypnotic in AD
      patients with disrupted sleep, but neither does it substantially worsen the
      recent memory deficits of AD.

PMID- 8577815
TI  - Benzodiazepine side effects: role of pharmacokinetics and pharmacodynamics.
AB  - Benzodiazepines have a wide variety of indications. However, CNS and psychiatric
      adverse reactions, tolerance, and withdrawal effects of benzodiazepines are
      becoming increasingly recognized and must be better understood for proper drug
      use. Certain benzodiazepines are associated with memory impairment and other
      cognitive defects and hyperexcitability phenomena during treatment (early-morning
      insomnia, daytime anxiety) and following withdrawal (rebound insomnia and
      anxiety, seizures). Elimination half-life, receptor-binding affinity, effects on
      the locus coeruleus-norepinephrine (LC-NE) and hypothalamic-pituitary-adrenal
      (HPA) axes, and the interaction of these factors appear to be major determinants
      of frequency and severity of these untoward effects. Rapid drug elimination and
      high receptor-binding affinity were initially suggested as primary underlying
      factors which determine frequency, severity, and type of the side effects of
      benzodiazepines during administration and withdrawal. Newer data and information
      on triazolobenzodiazepines indicate that these psychiatric adverse reactions also
      relate to whether the benzodiazepine has strong direct effects on the LC-NE and
      HPA systems. Initial suppression of the LC-NE and HPA systems is followed, on an
      interdose basis, by a significant rebound and activation. This repetitive pattern
      of suppression followed by rebound results in a neurophysiologic and behavioral
      sensitization (kindling) of the limbic system and consequently contributes to
      central nervous system and psychiatric adverse reactions. The tendency of certain
      of these side effects to worsen over time supports empirically this
      neurophysiologic and biochemical model.

PMID- 8577816
TI  - Cardiovascular and antilipolytic effects of the adenosine agonist GR79236.
AB  - Adenosine is known to produce cardiovascular effects such as bradycardia and
      hypotension via activation of myocardial (A1) and vascular (A2) receptors and
      antilipolytic effects through activation of adipocyte (A1) receptors. We
      established the cardiovascular and antilipolytic profile of the adenosine A1
      agonist GR79236 (N6-[(1S,trans)-2-hydroxycyclopentyl]-adenosine) and compared it
      with CPA (N6-cyclopentyl-adenosine). GR79236 was approximately 3-fold less potent
      than CPA in inhibiting in vitro lipolysis. In conscious rats, both agents were
      shown to have antilipolytic and glucose-lowering properties. In rats instrumented
      with telemetry transmitters, orally administered CPA was one log unit more potent
      than GR79236 as a hypotensive and bradycardiac agent. In summary, GR79236 is an
      A1-selective adenosine agonist which reduces heart rate and mean arterial
      pressure and produces decreased plasma lipids and glucose levels.

PMID- 8577817
TI  - DL-tetrahydropalmatine-produced hypotension and bradycardia in rats through the
      inhibition of central nervous dopaminergic mechanisms.
AB  - The effects of DL-tetrahydropalmatine (THP; a main active substance of the
      Chinese herb corydalis), haloperidol (a dopamine D2 receptor antagonist),
      apomorphine and amphetamine on cardiovascular function and striatal dopamine (DA)
      release were compared in rats under general anesthesia. Intravenous
      administration of THP (1-10 mg/kg) or haloperidol (0.5-1.25 mg/kg) produced
      hypotension, bradycardia and increased DA release in the striatum. On the other
      hand, amphetamine (0.5-1.25 mg/kg) produced hypertension, tachycardia and
      increased striatal DA release. However, intravenous injection of apomorphine (0.5
      1.25 mg/kg) produced hypotension, bradycardia and decreased striatal DA release.
      In addition, the THP-induced hypotension was attenuated by pretreatment with
      spinal transection or amphetamine, while the THP-induced bradycardia was
      attenuated by pretreatment with bilateral vagotomy or amphetamine. Thus, it
      appears that THP acts through DA D2 receptor antagonism to induce hypotension and
      bradycardia in rats.

PMID- 8577818
TI  - Stimulating activity of A-4166 on insulin release in in situ hamster pancreatic
      perfusion.
AB  - Using the in situ hamster pancreatic perfusion system, the stimulating action of
      A-4166 on insulin release was examined in comparison with that of glibenclamide.
      Both antidiabetic agents stimulated insulin release, but its onset by A-4166 was
      faster than that by glibenclamide. In the presence of a basal glucose
      concentration (3 mmol/l), insulin releases induced by A-4166 and glibenclamide
      were inhibited by preexisting diazoxide. At higher glucose concentrations (5-16.7
      mmol/l), however, A-4166 was able to reverse the inhibitory effect of diazoxide
      on the first and second phases of insulin release, while glibenclamide did not
      reverse the first-phase release. On the other hand, in the presence of 16.7
      mmol/l of glucose A-4166 completely reversed the inhibitory action of diazoxide
      added simultaneously, but glibenclamide reversed it only partially. In the
      presence of 8 mmol/l of glucose, the stimulating action of A-4166 and
      glibenclamide on insulin release was hardly affected by inhibitors of ATP
      production. These results indicate that the stimulating action of A-4166 on
      insulin release is different from glibenclamide in response to the inhibitory
      action of diazoxide. These results also suggest that A-4166 is an effective agent
      for release of insulin by acting on the KATP channel, especially under an
      impaired function of pancreatic B cells.

PMID- 8577819
TI  - Depletion of cytochrome P-450 by thyroid hormone and cobalt-protoporphyrin IX in
      rat liver: evidence that susceptibility varies among forms of the heme protein.
AB  - The ability of 3,5,3'-triiodothyronine (T3) and cobalt-protoporphyrin LX (CoPP)
      to alter the levels of the cytochrome P-450 isoforms, CYP3A2, CYP2E1, CYP2B1 and
      CYP2B2, was examined in vitro in thyroidectomized adult male rats. With the
      exception of CYP2B2, CoPP administration resulted in a decline in each of the
      cytochrome P450 isoforms examined. The effects of T3 administration on
      immunoreactive levels of cytochrome P-450 were also examined in the liver of
      thyroidectomized rats. T3 treatment produced a marked depletion in all four
      cytochrome P-450 isoforms examined. Moreover, this T3-mediated depletion of
      hepatic cytochrome P-450 occurred in the absence of elevated heme oxygenase
      levels but in the presence of increased delta-aminolevulinate synthase activity.
      Thus, CoPP and T3 appear capable of producing isoform-specific downregulation of
      cytochrome P-450 in the liver of thyroidectomized rats. Based on relative levels
      of immunoreactive protein, the phenobarbital-inducible isoforms, CYP2B1 and
      CYP2B2, are most susceptible to T3-mediated suppression. Evidence is presented to
      suggest that these agents elicit these effects by entirely different mechanisms.

PMID- 8577820
TI  - Effects of cyclic adenosine monophosphate-dependent protein kinase and calcium
      dependent protein kinase modulators on stimulated gastric acid secretion in the
      perfused rat stomach.
AB  - The effects of cyclic adenosine monophosphate-dependent protein kinase (PKA) and
      calcium-dependent protein kinase (PKC) modulators on secretagogue-stimulated
      gastric acid secretion were studied in the continuously perfused stomach of the
      anesthetized rat. Intravenous histamine (0.25 mg/kg/h) and pentagastrin (2
      micrograms/kg/h) increased secretion above baseline by three- and fourfold,
      respectively. Parenteral administration of a PKC activator, 12-o
      tetradecanoylphorbol-13-acetate (TPA; 0.1 nmol/h), decreased histamine- and
      pentagastrin-stimulated secretion by 64 and 40%, respectively. Administration of
      PKC inhibitors, calphostin C and 1-(5-isoquinolinyl sulfonyl)-2 methylpiperazine
      (H-7; 10 nmol/h, each), increased histamine- and pentagastrin-stimulated
      secretion by 115 and 74% and 42 and 79%, respectively, while equimolar
      concentrations (10 nmol/h) of three other isoquinoline sulfonamides (HA-1004, H
      8, and H-89) had no effect, except for H-89 (100 nmol/h) which inhibited the
      histamine- and penta-gastrin-stimulated acid secretion by 44%. Basal secretion
      was not significantly altered by the aforementioned drugs. The TPA-induced
      inhibition of pentagastrin-stimulated secretion was partially reversed by
      treatment with H-7. These findings support a role of PKA and PKC in the
      modulation of stimulated gastric acid secretion in vivo.

PMID- 8577821
TI  - Protein kinases and phosphatases that act on histidine, lysine, or arginine
      residues in eukaryotic proteins: a possible regulator of the mitogen-activated
      protein kinase cascade.
AB  - Phosphohistidine goes undetected in conventional studies of protein
      phosphorylation, although it may account for 6% of total protein phosphorylation
      in eukaryotes. Procedures for studying protein N- kinases are described. Genes
      whose products are putative protein histidine kinases occur in a yeast and a
      plant. In rat liver plasma membranes, activation of the small G-protein, Ras,
      causes protein histidine phosphorylation. Cellular phosphatases dephosphorylate
      phosphohistidine. One eukaryotic protein histidine kinase has been purified, and
      specific proteins phosphorylated on histidine have been observed. There is a
      protein arginine kinase in mouse and protein lysine kinases in rat. Protein
      phosphohistidine may regulate the mitogen-activated protein kinase cascade.

PMID- 8577822
TI  - Clinical pharmacokinetics of new antiepileptic drugs.
AB  - We have reviewed the pharmacokinetics of six antiepileptic drugs that are
      marketed (felbamate, gabapentin, lamotrigine, oxcarbazepine, vigabatrin, and
      zonisamide) and six drugs that are undergoing evaluation (levetiracetam,
      ralitoline, remacemide, stiripentol, tiagabine, and topiramate). In addition, we
      have compared the prodrugs eterobarb and fosphenytoin and the controlled-release
      formulations of valproic acid and carbamazepine with their parent compounds.
      Finally, we have devised a scoring system to compare the pharmacokinetics of new
      antiepileptic drugs. Using this system, vigabatrin, levetiracetam, gabapentin,
      and topiramate appea to have the most favourable pharmacokinetic profiles, whilst
      ralitoline and stiripentol have the least favourable.

PMID- 8577823
TI  - Cholinergic and vasoactive intestinal polypeptidergic innervation of the cerebral
      arteries.
AB  - Acetylcholine and vasoactive intestinal polypeptide are not only two vasoactive
      agonists that predominantly induce a vasodilatation of the cerebral arteries, but
      also correspond to neurotransmitters that innervate the various anatomical
      segments of the cerebral vasculature. The distinct patterns of the
      cerebrovascular cholinergic and vasoactive intestinal polypeptidergic
      innervation, their neurochemistry, in vitro and in vivo pharmacology, as well as
      the putative pathophysiological implications of these neurotransmission systems
      are critically summarized on the basis of the most recently published literature.

PMID- 8577824
TI  - Treatment of childhood epilepsy.
AB  - Epilepsy in children is frequently misdiagnosed and inappropriately managed with
      major medical, social, and educational consequences. The advent of the newer anti
      epileptic drugs has paradoxically, and in contrast to what was expected,
      contributed to a therapeutic confusion, which in certain instances, has
      perpetuated this unsatisfactory management. The purpose of this paper is to
      address some of the diagnostic and management issues and outline drug regimens
      for specific seizures types and epilepsy syndromes. Alternative and surgical
      therapies, and the treatment of neonatal and 'febrile seizures' and status
      epilepticus will not be discussed in detail, as these particular aspects fall
      outside the remit of this paper.

PMID- 8577825
TI  - New targets for lipid lowering and atherosclerosis prevention.
AB  - The effectiveness of plasma lipid lowering in the clinic is well supported by a
      growing number of contributions, indicating the significant improvement in
      cardiovascular risk in primary and particularly in secondary prevention. While
      these studies have clearly indicated that the more potent agents for cholesterol
      reduction can provide a very effective help, other pathways of lipid metabolism
      have gained interest. These should be evaluated, in the hope of providing a more
      complete answer to the question of regulating lipid absorption, distribution, and
      tissue deposition. In addition to newer more potent systemic lipid-lowering drugs
      (in particular hydroxymethylglutaryl coenzyme A reductase inhibitors),
      nonsystemic agents, including cholesterol sequestrants, are receiving attention.
      Some of these are effective at low concentrations, thus providing a potentially
      powerful tool for plasma cholesterol regulation. Another area of development is
      that of acyl coenzyme A cholesterol acyltransferase inhibitors, i.e., drugs
      interfering with cholesterol esterification in tissues, particularly in the
      arterial wall; the major problem with these seems to be that of poor tolerability
      and of lack of definitive proof of plasma cholesterol reduction in humans. At
      present, drugs for the treatment of elevated lipoprotein(a) levels are not
      available, with few exceptions; in this case, a better understanding of the
      regulation of lipoprotein(a) metabolism and of the potential benefit of treatment
      seems necessary. Elevation of congenitally low high density lipoprotein
      cholesterol levels may also be an important target: microsomal enzyme inducers
      have been tested, but have not provided a clinically significant response; drugs
      with a mixed endocrine-hypolipidemic activity possibly may prove effective. Other
      targets, e.g., the correction of the lipoprotein pattern characterized by "small
      low density lipoprotein," and the development of drugs specifically acting on the
      cholesteryl ester transfer protein and lipoprotein lipase systems, are being
      explored. Finally, new areas of development are in recombinant apolipoproteins
      (apo's) and in gene therapy. One case, i.e., that of apo A-I/HDL, is entering the
      clinical field; the mutant apo A-IMilano might provide help because of a combined
      cholesterol removing/fibrinolytic activity. In the case of gene therapy, at
      present, data on low density lipoprotein receptor replacement are encouraging.
      Further options, such as gene transfer in the arterial wall to induce vascular
      protection/disobliteration of occlusions, are also being tested.

PMID- 8577826
TI  - An evaluation of the use of multidimensional scaling for understanding brain
      connectivity.
AB  - A large amount of data is now available about the pattern of connections between
      brain regions. Computational methods are increasingly relevant for uncovering
      structure in such datasets. There has been recent interest in the use of non
      metric multidimensional scaling (NMDS) for such analysis. NMDS produces a spatial
      representation of the 'dissimilarities' between a number of entities. Normally,
      it is applied to data matrices containing a large number of levels of
      dissimilarity, whereas for brain connectivity data there is a very small number.
      We address the suitability of NMDS for this case. Systematic numerical studies
      are presented to evaluate the ability of this method to reconstruct known
      geometrical configurations from dissimilarity data processing few levels. In this
      case there is a strong bias for NMDS to produce annular configurations, whether
      or not such structure exists in the original data. For the case of a connectivity
      dataset derived from the primate cortical visual system, we demonstrate that
      great caution is needed in interpreting the resulting configuration. Application
      of an independent method that we developed also strongly suggests that the visual
      system NMDS configuration is affected by an annular bias. We question the
      strength of support that an NMDS analysis of the visual system data provides for
      the two streams view of visual processing.

PMID- 8577827
TI  - Non-metric multidimensional scaling in the analysis of neuroanatomical connection
      data and the organization of the primate cortical visual system.
AB  - Neuroanatomists have established that the various gross structures of the brain
      are divided into a large number of different processing regions and have
      catalogued a large number of connections between these regions. The connectional
      data derived from neuroanatomical studies are complex, and reliable conclusions
      about the organization of brain systems cannot be drawn from considering them
      without some supporting analysis. Recognition of this problem has recently led to
      the application of a variety of techniques to the analysis of connection data.
      One of the techniques that we previously employed, non-metric multidimensional
      scaling (NMDS), appears to have revealed important aspects of the organization of
      the central nervous system, such as the gross organization of the whole cortical
      network in two species. We present here a detailed treatment of methodological
      aspects of the application of NMDS to connection data. We first examine in detail
      the particular properties of neuroanatomical connection data. Second, we consider
      the details of NMDS and discuss the propriety of different possible NMDS
      approaches. Third, we present results of the analyses of connection data from the
      primate visual system, and discuss their interpretation. Fourth, we study
      independent analyses of the organization of the visual system, and examine the
      relation between the results of these analyses and those from NMDS. Fifth, we
      investigate quantitatively the performance of a number of data transformation and
      conditioning procedures, as well as tied and untied NMDS analysis of
      untransformed low-level data, to determine how well NMDS can recover known metric
      parameters from artificial data. We then re-analyse real connectivity data with
      the most successful methods at removing the effects of sparsity, to ensure that
      this aspect of data structure does not obscure others. Finally, we summarize the
      evidence on the connectional organization of the primate visual system, and
      discuss the reliability of NMDS analyses of neuroanatomical connection data.

PMID- 8577828
TI  - Space, persistence and dynamics of measles epidemics.
AB  - This paper explores the relations between persistence and dynamics in measles
      epidemics. Most current models, including the stochastic seasonally forced and
      age-structured models examined here, fail to capture simultaneously the observed
      dynamics and persistence characteristics of epidemics in large urban populations
      before vaccination. Summary measures of persistence and trienniality allow us to
      compare epidemics in England, New York and Copenhagen with results of non-spatial
      and spatial stochastic models. Spatial (metapopulation) structure allow
      persistence and triennial dynamics to coexist i this class of models. The spatial
      dynamics of measles, for which detailed spatiotemporal data are available, may
      serve as a useful test of ideas applicable to other epidemiological and
      ecological systems with an important spatial component.

PMID- 8577829
TI  - Slow coevolution of a viral pathogen and its diploid host.
AB  - We study a population exposed to a lethal infectious disease. Host response is
      carried at one locus with two alleles while the pathogen occurs in two variants.
      Based on an SI-type epidemic model we derive explicit equations for the dynamics
      of each genotype. By assuming small variations in both host and disease, we
      obtain a separation in time scales between epidemic and evolutionary processes.
      This allows us to describe explicitly the changes in host and disease gene
      frequencies. The resulting model has a rich behaviour including multiple stable
      states and oscillations. However, in the oscillatory situation the model is
      degenerate excluding the possibility of limit cycles. We show that the degeneracy
      can only be removed by frequency dependent selection in the pathogen, for example
      by including direct interaction of virus in a free-living stage. The qualitative
      conclusions extend to an SIR-type epidemic model, where recovery with immunity
      from the disease is possible.

PMID- 8577830
TI  - The evolution of exploitation and honesty in animal communication: a model using
      artificial neural networks.
AB  - Conflicts of interest arise between signaller and receiver in most kinds of
      biological communication. Some authors have argued that this conflict is likely
      to give rise to deceit and exploitation, as receivers lag behind in the
      coevolutionary 'arms race' with signallers. Others have argued that such
      manipulation is likely to be short-lived and that receivers can avoid being
      deceived by paying attention to signals that are costly and hence 'unfakeable.'
      These two views have been hard to reconcile. Here, we present results from
      simulations of signal evolution using artificial neural networks, which
      demonstrate that honesty can coexist with a degree of exploitation. Signal cost
      ensures that receivers are able to obtain some honest information, but is unable
      to prevent exploitative signalling strategies from gaining short-term benefits.
      Although any one receiver bias that is open to exploitation will subsist for only
      a short period of time once signallers begin to take advantage of it, new
      preferences of this kind are constantly regenerated through selection and random
      drift. Hidden preferences and sensory exploitation are thus likely to have an
      enduring influence on the evolution of honest, costly signals. At the same time,
      honesty and cost are prerequisites for the evolution of exploitation. When
      signalling is cost-free, selection cannot act to maintain honesty, and receivers
      rapidly evolve to ignore signals. This leads to a reduction in the extent of
      hidden preference, and a consequent loss of potential for exploitation.

PMID- 8577831
TI  - Evolution of the cell theory.
AB  - The problem of the nature of life has a long history going back to the Greeks.
      There was little real progress until the 19th century and Aristotle may have been
      at home with many 18th century ideas about vital forces and basic units. Although
      Hooke described cells in 1665 it took a further 200 years for the significance
      and nature of cells to be appreciated. In the mid 18th century some considered
      the basic building blocks of living matter to be fibrous. Globular theories, the
      precursor to the cell theory, were quite popular at the beginning of the 19th
      century. Many workers, as microscopes improved, had described various cell types
      and structures including the nucleus but the idea that cells were the universal
      units is associated with in 1838 and that of Schwann in 1839. However, Schwann
      mistakenly thought that cells could form de novo. Cell division was established
      by Remak and others in the 1850s. Mitosis was first understood by Flemming in
      1882. The existence of the animal cell membrane was only established by the
      beautiful experiments of Overton in 1895. The history of the cell theory can be
      used to show that progress can be based on incorrect but productive ideas. It is
      one of the most important ideas in all of biology.

PMID- 8577832
TI  - Evolution of eukaryotic cellular processes.

PMID- 8577833
TI  - The origins and evolution of eukaryotic proteins.
AB  - The common ancestry of eukaryotes, archaebacteria and eubacteria is well
      demonstrated by amino acid sequence comparisons of numerous proteins that are
      common to all three groups. On the other hand, there are a few proteins, like
      ubiquitin, that are common to eukaryotes and archaebacteria and which have yet to
      be observed in eubacteria. Some proteins appear to be wholly restricted to
      eukaryotes; this is especially true of cytoskeletal proteins. Recently, actin has
      been found by crystallography to be homologous with an ATP-binding domain found
      in a heat shock protein and several other proteins common to all three
      urkingdoms. This observation is puzzling on several counts. Most cytoskeletal
      proteins like actin and tubulin are very slow changing and must have been so for
      a very long time. How is it, then, that no sequence resemblance can be discerned
      with their alledged prokaryotic antecedents? The question is addressed by
      considering two bacterial fts proteins which appear to be related to actin, on
      the one hand, and tubulin, on the other. One answer may be that the rate of
      change of these proteins changed dramatically at a key point in their history.
      Another possibility is that eukaryotes are much older than some of their other
      proteins indicate.

PMID- 8577834
TI  - DNA sequence evolution: the sounds of silence.
AB  - Silent sites (positions that can undergo synonymous substitutions) in protein
      coding genes can illuminate two evolutionary processes. First, despite being
      silent, they may be subject to natural selection. Among eukaryotes this is
      exemplified by yeast, where synonymous codon usage patterns are shaped by
      selection for particular codons that are more efficiently and/or accurately
      translated by the most abundant tRNAs; codon usage across the genome, and the
      abundance of different tRNA species, are highly co-adapted. Second, in the
      absence of selection, silent sites reveal underlying mutational patterns. Codon
      usage varies enormously among human genes, and yet silent sites do not appear to
      be influenced by natural selection, suggesting that mutation patterns vary among
      regions of the genome. At first, the yeast and human genomes were thought to
      reflect a dichotomy between unicellular and multicellular organisms. However, it
      now appears that natural selection shapes codon usage in some multicellular
      species (e.g. Drosophila and Caenorhabditis), and that regional variations in
      mutation biases occur in yeast. Silent sites (in serine codons) also provide
      evidence for mutational events changing adjacent nucleotides simultaneously.

PMID- 8577835
TI  - Transcriptional noise and the evolution of gene number.
AB  - Several proposals are made to explain the apparent increase in complexity of
      certain lineages during evolution. The proposals (not made in this order) are:
      (1) that gene number is a valid measure of biological complexity; (2) that gene
      number has not increased continuously during evolution, but has risen in discrete
      steps; (3) that two of the biggest steps occurred at the transition from
      prokaryotes to eukaryotes and the transition from invertebrates to vertebrates;
      (4) that these steps were made possible by 'systemic' changes in the way that
      genetic information is managed in the genome; (5) that the ability to silence
      inappropriate promoters is the primary limitation on gene number; (6) that the
      invention of nucleosomes (and perhaps the nuclear membrane) facilitated the
      evolution of eukaryotes from prokaryotic ancestors; (7) that the spread of low
      density methylation throughout the genome facilitated the evolution of
      vertebrates from invertebrate ancestors.

PMID- 8577836
TI  - Transcriptional repression in the Drosophila embryo.
AB  - Transcriptional repression is essential for the conversion of crude maternal
      gradients into sharp territories of tissue differentiation in the Drosophila
      embryo. Evidence will be presented suggesting that some of the embryonic
      repressors function through a short-range 'quenching' mechanism, whereby a
      repressor works over short distances (ca. 50 b.p.) to block neighbouring
      activators within a target enhancer. This type of repression can explain how
      different enhancers work autonomously within complex modular promoters. However,
      at least one of the repressors operating in the early embryo works through a long
      range, or silencing, mechanism. The binding of a silencer to a given enhancer
      leads to the inactivation of all enhancers within a complex promoter. The
      analysis of chromatin boundary elements suggest that silencers and enhancers
      might work through distinct mechanisms. We speculate that silencers constrain the
      evolution of complex promoters.

PMID- 8577837
TI  - The sodium pump in the evolution of animal cells.
AB  - Plant cells and bacterial cells are surrounded by a massive cellulose wall, which
      constrains their high internal osmotic pressure (tens of atmospheres). Animal
      cells, in contrast, are in osmotic equilibrium with their environment, have no
      restraining surround, can take on a variety of shapes and change these from
      moment to moment. This osmotic balance is achieved by the action of the energy
      consuming sodium pump, one of the P-type ATPase transport protein family, members
      of which are indeed also found in bacteria. The pump's action brings about a
      transmembranal electrochemical gradient of sodium ions, harnessed in a range of
      transport systems that couple the dissipation of this gradient to establishing a
      gradient of the coupled substrate. The primary role of the sodium pump as a
      regulator of cell volume has evolved to provide the basis for an enormous variety
      of physiological functions.

PMID- 8577838
TI  - Evolution of the cell cycle.
AB  - Cell proliferation involves duplication of all cell constituents and their more
      or-less equal segregation to daughter cells. It seems probable that the
      performance of primitive cell-like structures would have been dogged by poor
      duplication and segregation fidelity, and by parasitism. This favoured evolution
      of the genome and with it the distinction between 'genomic' components like
      chromosomes whose synthesis is periodic and most other 'functional' components
      whose synthesis is continuous. Eukaryotic cells evolved from bacterial ancestors
      whose fused genome was replicated from a single origin and whose means of
      segregating sister chromatids depended on fixing their identity at replication.
      Evolution of an endo- or cytoskeleton, initially as means of consuming other
      bacteria, eventually enabled evolution of the mitotic spindle and a new means of
      segregating sister chromatids whose replication could be initiated from multiple
      origins. In this primitive eukaryotic cell, S and M phases might have been
      triggered by activation of a single cyclin-dependent kinase whose destruction
      along with that of other proteins would have triggered anaphase. Mitotic non
      disjunction would have greatly facilitated genomic expansion, now possible due to
      multiple origins, and thereby accelerated the tempo of evolution when permitted
      by environmental conditions.

PMID- 8577839
TI  - GTPases: a family of molecular switches and clocks.
AB  - Members of the GTPase superfamily share a core domain with a conserved three
      dimensional structure and a common GTPase cycle, but perform a wide variety of
      regulatory tasks in eukaryotic cells. Evolution has created functional diversity
      from the conserved GTPase structure in two principal ways: (i) by combining in
      the product of a single gene the core GTPase domain attached to one or more
      additional folded domains; (ii) by building around a core GTPase an assembly of
      proteins encoded by different genes. Analysis of the patterns of conserved amino
      acid side chains on surfaces of G alpha proteins reveals interfaces with other
      proteins in the G-protein signal linking device.

PMID- 8577840
TI  - Intracellular membrane morphology.
AB  - The membrane-bound organelles on the exocytic and endocytic pathways are linked
      by vesicles which bud from one membrane compartment, carrying selected cargo, and
      fuse with the next on the pathway. The principles underlying this vesicle
      mediated traffic go a long way towards explaining the morphology of these
      intracellular organelles and their behaviour during mitosis.

PMID- 8577841
TI  - Evolution of a dynamic cytoskeleton.
AB  - Actin filaments and microtubules form the cytoskeleton of all eukaryotic cells,
      and they are responsible for organizing the cytoplasm and supporting motile
      processes. Both polymers are highly dynamic, and their polymerization dynamics
      are central to their organization. Though their evolutionary origins appear to be
      distinct, actin and tubulin have a similar mechanism for promoting polymerization
      dynamics in which the energy of nucleotide triphosphate hydrolysis during
      polymerization is used to weaken the bonds between subunits, thus promoting
      subsequent depolymerization. The evolutionary origins of actin and tubulin are
      unclear. It is likely that motile mechanisms driven by reversible polymerization,
      termed thermal ratchets, are older than those based on ATPase motor proteins.
      Such mechanisms are still important in modern eukaryotes, and may have powered
      early versions of the critical motile processes of phagocytosis and chromosome
      segregation in primitive cells. Thus evolution of dynamic cytoskeletal polymers
      may have been one of the earliest and most important steps leading to the
      evolution of eukaryotes. Plausible evolutionary pathways can be constructed
      leading from simple enzymes to dynamic cytoskeletal polymers.

PMID- 8577842
TI  - Developmental control of N-CAM expression by Hox and Pax gene products.
AB  - A mounting body of evidence suggests that cell-cell adhesion molecules (CAMs)
      play critical roles in morphogenetic patterning. Perturbations of CAM binding can
      lead to altered tissue pattern and interruption of tissue interactions can lead
      to altered patterns of CAM expression. These observations focus attention on the
      factors responsible for the place-dependent expression of adhesion molecules such
      as N-CAM, the neural cell adhesion molecule. Our recent experiments in vitro
      indicate that transcription factors encoded by Hox and Pax genes bind to specific
      DNA sequences in the N-CAM promoter and activate that promoter. In particular, a
      region of the N-CAM promoter designated the homeodomain binding site (HBS)
      interacts with a variety of different homeodomain proteins. A different region of
      the N-CAM promoter binds to the paired domain of Pax proteins. These
      transcription factors differentially regulate the N-CAM gene. Such in vitro
      studies suggest that the N-CAM gene may be an in vivo target for homeobox and Pax
      gene products. Recent experiments on transgenic mice carrying normal and mutated
      segments of the N-CAM promoter linked to a lacZ reporter gene suggest that the N
      CAM regulation observed in vitro actually has counterparts in vivo. The
      significance of these observations is that they connect gene products capable of
      morphoregulation (such as CAMs) to pattern-forming genes.

PMID- 8577843
TI  - Hox genes and the evolution of diverse body plans.
AB  - Homeobox genes encode transcription factors that carry out diverse roles during
      development. They are widely distributed among eukaryotes, but appear to have
      undergone an extensive radiation in the earliest metazoa, to generate a range of
      homeobox subclasses now shared between diverse metazoan phyla. The Hox genes
      comprise one of these subfamilies, defined as much by conserved chromosomal
      organization and expression as by sequence characteristics. These Hox genes act
      as markers of position along the antero-posterior axis of the body in nematodes,
      arthropods, chordates, and by implication, most other triploblastic phyla. In the
      arthropods this role is visualized most clearly in the control of segment
      identity. Exactly how Hox genes control the structure of segments is not yet
      understood, but their differential deployment between segments provides a model
      for the basis of segment diversity. Within the arthropods, distantly related
      taxonomic groups with very different body plans (insects, crustaceans) may share
      the same set of Hox genes. The expression of these Hox genes provides a new
      character to define the homology of different body regions. Comparisons of Hox
      gene deployment between insects and a branchiopod crustacean suggest a novel
      model for the derivation of the insect body plan.

PMID- 8577844
TI  - Selfish genetic elements and their role in evolution: the evolution of sex and
      some of what that entails.
AB  - An individual is often considered (sometimes implicitly) to be the product of a
      well functioning mutualism between its constituent genes. This however need not
      be so. One consequence of sexual reproduction is that costly competition within
      an individual between genes that are effectively allelic can provide the
      conditions for the spread of suppressors of such competition. The spread of both
      these ultracompetitive alleles (alias selfish genetic elements) and their
      suppressors is evidence of a 'conflict of interests' within the genome. That this
      conflict is a potentially important force in the evolution of genetic systems is
      illustrated by consideration of the problem of the evolution of sexes (alias
      mating types). One hypothesis holds that sexes are the result of selection on
      nuclear genes to coordinate the inheritance of cytoplasmic genomes (usually this
      means the enforcement of uniparental inheritance) so as to prevent competition
      between unrelated cytoplasmic genomes. This hypothesis is tested against five
      comparative predictions and shown to receive considerable empirical support.

PMID- 8577845
TI  - Summing up: conservation and diversification in metazoan eukaryotic cells.

PMID- 8577846
TI  - Pattern formation in the Arabidopsis embryo: a genetic perspective.
AB  - During embryogenesis, a single cell gives rise to different cell types, tissues
      and organs which are arranged in a biologically meaningful context, or pattern.
      The resulting basic body organization of higher plants, which is expressed in the
      seedling, provides a reference system for postembryonic development during which
      the meristems of the shoot and the root produce the adult body. The seedling may
      be viewed as the superimposition of two patterns: one along the apical-basal axis
      of polarity and the other perpendicular to the axis. To analyse mechanisms
      underlying pattern formation in the embryo, a genetic approach has been taken in
      Arabidopsis. Mutations in a small number of genes alter one or the other of the
      two patterns. The mutant phenotypes suggest that early partitioning of the axis
      is followed by region-specific development, including the formation of the
      primary shoot and root meristems. The cloning of two genes involved in pattern
      formation provides a basis for mechanistic studies of how cells adopt specific
      fates in the developing embryo.

PMID- 8577847
TI  - Regulation of flowering time: Arabidopsis as a model system to study genes that
      promote or delay flowering.
AB  - The time that plants flower is often tightly regulated and adapted to the
      locations in which they grow. The basis of this regulation has been analysed
      using genetic and physiological approaches since the early decades of this
      century. The study of flowering time in the model plant species Arabidopsis
      thaliana has allowed many genes involved in regulating flowering time to be
      identified as mutations, and for the genetic interactions between these mutations
      to have been studied. Furthermore, two genes required to promote flowering of
      Arabidopsis have recently been isolated, and their sequences have provided some
      insight into the identity of proteins involved in regulating flowering time.

PMID- 8577848
TI  - Cellular and molecular events in a newly organizing lateral root meristem.
AB  - Spontaneous or auxin-induced lateral root formation in radish and Arabidopis
      provides an efficient system in which to examine molecular and cellular events
      associated with the initiation of a new meristem. Subtracted cDNA libraries made
      at different times in lateral root initiation were used as a source of genes that
      are expressed differentially during this developmental process, and expression
      studies on a small gene family of ribosomal protein genes were conducted. From
      analysis of cell division patterns in pericycle cells the number of founder cells
      for lateral roots was established. By the use of in vitro growth assays lateral
      root formation was determined to be a two-stage process. First a primordium is
      formed, and subsequently a subset of primordial cells begins to function as the
      lateral root apical meristem. This mode of root development has implications for
      pattern formation in newly organizing organs.

PMID- 8577849
TI  - Homeobox genes in the functioning of plant meristems.
AB  - The maize homebox gene knotted1 (kn1) is expressed in vegetative and floral
      meristems and is down-regulated at the site of primordia formation. kn1-related
      genes from maize and other species also show meristem-specific expression and
      offer additional tools for studying the activities of shoot meristems. Members of
      this gene family are expressed early in embryogenesis, providing molecular
      markers for meristem initiation. Ectopic expression of either kn1 or a related
      Arabidopsis gene, KNAT1, causes dramatic alterations in Arabidopsis and tobacco
      leaf morphology. Most significantly, meristems form on the leaf, producing small
      shoots. We discuss whether the phenotypes can be interpreted as changes in
      positional information or timing of determination.

PMID- 8577850
TI  - A novel cell-ablation strategy for studying plant development.
AB  - The processes controlling the differentiation of plant cells are not well
      understood. Two alternative, but not mutually exclusive, mechanisms probably play
      a major role in plant-cell differentiation. One mechanism utilizes a position
      independent, cell-autonomous differentiation process. The other, employs a
      position-dependent, cell-cell interaction process that requires signals from
      neighbouring cells. Cell ablation studies can be used to distinguish between
      these two models of plant-cell differentiation. In this article we outline a new
      cell-ablation strategy that utilizes promoters with distinct, but overlapping,
      cell specificities that are fused with cytotoxic and anticytotoxic structural
      genes. We present preliminary observations on how this strategy can be used to
      dissect the events controlling anther development.

PMID- 8577851
TI  - Signal-transduction pathways controlling light-regulated development in
      Arabidopsis.
AB  - All metazoan cells are able to make decisions about cell division or cellular
      differentiation based, in part, on environmental cues. Accordingly, cells express
      receptor systems that allow them to detect the presence of hormones, growth
      factors and other signals that manipulate the regulatory processes of the cell.
      In plants, an unusual signal-light-is required for the induction and regulation
      of many developmental processes. Past physiological and molecular studies have
      revealed the variety and complexity of plant responses to light but until
      recently very little was known about the mechanisms of those responses. Two major
      breakthroughs have allowed the identification of some photoreceptor signalling
      intermediates: the identification of photoreceptor and signal transduction
      mutants in Arabidopsis, and the development of single-cell microinjection assays
      in which outcomes of photoreceptor signalling can be visualized. Here, we review
      recent genetic advances which support the notion that light responses are not
      simply endpoints of linear signal transduction pathways, but are the result of
      the integration of a variety of input signals through a complex network of
      interacting signalling components.

PMID- 8577852
TI  - Phytochrome signal-transduction: characterization of pathways and isolation of
      mutants.
AB  - The study of phytochrome signalling has yielded a wealth of data describing both
      the perception of light by the receptor, and the terminal steps in phytochrome
      regulated gene expression by a number of transcription factors. We are now
      focusing on establishing the intervening steps linking phytochrome
      photoactivation to gene expression, and the regulation and interactions of these
      signalling pathways. Recent work has utilized both a pharmacological approach in
      phototrophic soybean suspension cultures and microinjection techniques in tomato
      to establish three distinct phytochrome signal-transduction pathways: (i) a
      calcium-dependent pathway that regulates the expression of genes encoding the
      chlorophyll a/b binding protein (CAB) and other components of photosystem II;
      (ii) a cGMP-dependent pathway that regulates the expression of the gene encoding
      chalcone synthase (CHS) and the production of anthocyanin pigments; and (iii) a
      pathway dependent upon both calcium and cGMP that regulates the expression of
      genes encoding components of photosystem I and is necessary for the production of
      mature chloroplasts. To study the components and the regulation of phytochrome
      signal-transduction pathways, mutants with altered photomorphogenic responses
      have been isolated by a number of laboratories. However, with several possible
      exceptions, little real progress has been made towards the isolation of mutants
      in positive regulatory elements of the phytochrome signal-transduction pathway.
      We have characterized a novel phytochrome A (PhyA)-mediated far-red light (FR)
      response in Arabidopsis seedlings which we are currently using to screen for
      specific phyA signal-transduction mutants.

PMID- 8577853
TI  - Genetic analysis of a seedling stress response to ethylene in Arabidopsis.
AB  - A genetic framework has been devised for the action of genes within the ethylene
      response pathway. This working model is based on the epistatic interactions among
      a variety of ethylene response mutations. Most of the mutations that have been
      described act in a linear pathway. Genes controlling cell elongation in response
      to ethylene must, at some level, act to affect the architecture of the
      cytoskeleton. Genes that act late in the pathway, in mutant form, may lead to
      highly specific phenotypes such as the increased sensitivity to taxol in the ein6
      mutant. Analysis of these downstream components may provide critical insights
      into the nature of ethylene's effect on the cell elongation machinery.

PMID- 8577854
TI  - Calcium and the generation of plant form.
AB  - The involvement of mechanical signals (tension and compression) in the
      determination of the form of living organisms has been speculated upon for many
      years. These mechanical signals (both environmental and those generated within
      the plant itself) have significant effects on plant development and thus
      morphology. Plants respond to externally applied mechanical signals (touch and
      wind) by an immediate elevation of cytosolic calcium concentration ([Ca2+]eyt) in
      stimulated cells. This response requires the movement of plant tissues to cause
      tension and compression. Some of the more longer-term responses to mechanical
      signals, e.g. TCH gene expression and reduction in hypocotyl growth, show a
      calcium-dependency. It seems likely, therefore, that the effects of mechanical
      signals on plant development are mediated by the second messenger, calcium. This
      raises the exciting possibility that this simple ion plays a central role in the
      determination of plant form itself.

PMID- 8577855
TI  - Cell-context signalling.
AB  - In plants, cells differentiate according to their position with relation to their
      cell neighbours. Monoclonal antibody (MAb) probes to polysaccharide epitopes,
      present at the surfaces of all plant cells, have defined a family of proteoglycan
      antigens which signify cellular position. These MAbs have been used to sort the
      single cells present in carrot somatic cell cultures on the basis of the presence
      or absence of specific polysaccharide epitopes. This sorting allows embryo
      initial cells to be cultured among different cell collectives (based on their
      polysaccharide epitope expression) and thus in altered contextual backgrounds.
      These experiments have shown that specific populations of embryo initial
      precursor cells induce and sustain the early development of the embryo initials,
      revealing that the populations of different cell collectives which are defined by
      different polysaccharide epitopes (cell-context) serves important regulatory
      function in early plant development. Somatic embryo initials deprived of the
      influence of the cell collective-defined by the presence of the polysaccharide
      epitope recognised by the MAb JIM8-establish unorganised first divisions and
      develop as callus. However, in the presence of the JIM8-reactive cell collective,
      or medium conditioned by the collective, the initials develop into somatic
      embryos. This demonstrates that the cells defined by the JIM8 polysaccharide
      epitope are necessary to sustain the meristematic activity which drives the
      renewed development. Transfer of a cell-wall signal from the JIM8-reactive cells
      to cellular situations in carrot seedlings in which they would not normally occur
      (out-of-context signals) stimulates lateral root production, thus demonstrating
      that the inductive signal operative in suspension cultures can be reinterpreted
      by specific cells later in development and reinitiate meristematic activity. The
      communication between the precursor cells defined by JIM8 and embryo initials
      defines an early cell-cell interaction in developing carrot plants. Labelling of
      flower sections suggests that the same interaction exists between embryo apical
      and basal cells early in normal development.

PMID- 8577856
TI  - The development of cell pattern in the root epidermis.
AB  - The root epidermis of most angiosperms is composed of a patterned array of hair
      and non-hair cells. Hair cells may develop randomly in any location in the
      epidermis (type 1), from specialized cells that form as result of an asymmetric
      cell division in a mother cell (type 2) or cells may be arranged in files of one
      cell type or the other (type 3). The development of the epidermis in Arabidopsis
      has been examined in detail and corresponds to type 3 epidermal development. A
      combination of physiological and genetic observations indicates that ethylene is
      a positive regulator of root hair differentiation. Differential exposure of
      epidermal cells to ethylene as a result of the cellular geometry of the root may
      account for the wild-type epidermal pattern.

PMID- 8577857
TI  - The adaptive advantage of phenotypic memory in changing environments.
AB  - The adaptive value of carry-over effects, the persistence of induced phenotypes
      for several generations despite the change in the conditions that first induced
      these phenotypes, is studied in the framework of a simple model. Three different
      organismal strategies-non-inducible (genetic), completely inducible (plastic),
      and intermediate (carry-over)-are compared in fitness terms within three
      different environments. Analytical results and numerical simulations show that
      carry-over effects can have an advantage in stochastic environments even over
      organisms with high adaptive plasticity. We argue that carry-over effects
      represent an adaptive mechanism on the ecological timescale that fills the gap
      between short-term individual adaptations and long-term evolutionary adaptations.
      An extension of the concept of plasticity to incorporate the time dimension and
      include the stability of induced phenotypes through both clonal and sexual
      generations, is suggested.

PMID- 8577858
TI  - Evolutionary history of New and Old World vultures inferred from nucleotide
      sequences of the mitochondrial cytochrome b gene.
AB  - The phylogeny of 11 species of Old World vultures (Aves: Accipitriformes,
      Aegypiinae), three species of New World vultures (Cathartidae) and theri nearest
      relatives within and outside the order Accipitriformes was investigated based on
      1026 nucleotides of the mitochondrial cytochrome b gene. The data support the
      contention that New World vultures are not birds of prey, but phylogenetic
      information was insufficient to identify whether they are closer to storks
      (Ciconiidae) or to Accipitriformes. Four species of Gyps are all closely related
      and probably speciated within the Pleistocene. Molecular data do not support the
      split of 'white-backed' vultures from Gyps in a separate genus Pseudogyps. The
      monotypic genera of large, heavy-billed vultures, Aegypius, Torgos, Trigonoceps
      and Sarcogyps, are of monophyletic origin. We propose to merge Torgos with
      Aegypius, but retain Trigonoceps and Sarcogyps as separate genera, Sarcogyps
      being clearly the most primitive of the four. All four, together with Gyps and
      Necrosyrtes, form a monophyletic subfamily or 'core group', to which the
      subfamily Aegypiinae should be restricted. This group shares a more recent common
      ancestor with several non-vulture genera of Accipitrids, among them Buteo,
      Aquila, Haliaeetus and Circaetus, than it does with the two aberrent vultures
      Gypaetus barbatus and Neophron percnopterus. The last two are much more
      primitive; they seem to be each other's sister species and are closer to Pernis
      than to other Accipitrids. We propose separating Gypaetus and Neophron in the
      subfamily Gypaetinae. If the cytochrome b gene tree accurately reflects vulture
      phylogeny, Old World vultures are polyphyletic with the Aegypius-Gyps clade
      having evolved convergently to the more ancient Gypaetus and Neophron vultures.
      Polyphyly of Old World vultures, although in conflict with the DNA-DNA
      hybridization phylogeny of Sibley & Ahlquist (1990), is well supported by
      molecular, karyotypic, morphological and other phenotypic evidence (behaviour,
      voice) indicating fundamental differences between the two evolutionary lines.

PMID- 8577859
TI  - The Leeuwenhoek Lecture, 1995. Adaptation to life without oxygen.
AB  - The Earth was populated by anaerobic organisms for at least a thousand million
      years before the atmosphere became oxygenated and aerobes could evolve. Many
      bacteria like Escherichia coli retain the ability to grow under both aerobic and
      anaerobic conditions. Recent studies have revealed some global regulatory
      mechanisms for activating or repressing the expression of relevant genes in
      response to oxygen availability. These mechanisms ensure that the appropriate
      metabolic mode is adopted when bacteria switch between aerobic and anaerobic
      environments.

PMID- 8577860
TI  - Mechanisms of ultraviolet light-induced pigmentation.
AB  - Work in the past 8 years, particularly in the past 1-2 years, has greatly
      expanded our understanding of the mechanisms by which ultraviolet irradiation
      stimulates melanogenesis in the skin. A direct effect of UV photons on DNA
      results in up-regulation of the gene for tyrosinase, the rate-limiting enzyme in
      melanin synthesis, as well as an increase in cell surface expression of receptors
      for at least one of the several known keratinocyte-derived melanogenic factors,
      MSH. Direct effects of UV on melanocyte membranes, releasing DAG and arachidonic
      acid, may also play a role in the tanning response. Diacylglycerol may activate
      PKC-beta, which in turn phosphorylates and activates tyrosinase protein; the
      pathways by which products of other inflammatory mediator cascades may act on
      melanogenesis are unknown. The tanning response also relies heavily on UV
      stimulated increased production and release of numerous keratinocyte-derived
      factors including bFGF, NGF, endothelin-1 and the POMC-derived peptides MSH,
      ACTH, beta-LPH and beta-endorphin. These factors variably induce melanocyte
      mitosis, increase melanogenesis, enhance dendricity and prevent apoptotic cell
      death following the UV injury. Thus, events within the epidermal melanin unit
      conspire to maintain or increase melanocyte number, increase melanin pigment
      throughout the epidermis. Overall, ultraviolet-induced melanogenesis may be one
      part of a eukaryotic SOS response to damaging ultraviolet irradiation that has
      evolved over time to provide a protective tan in skin at risk of further injury
      from sun exposure. These recent insights into the mechanisms underlying
      ultraviolet-induced melanogenesis offer the opportunity for novel therapeutic
      approaches to minimizing acute and chronic photodamage in human skin.

PMID- 8577861
TI  - Protochlorophyllide reductase. III: Synthesis of a protochlorophyllide
      dihydroflavin complex.
AB  - A mild and efficient method of linking a dihydroflavin to the C-17 carboyxlic
      acid side chain of protochlorophyllide, without degradation of the sensitive E
      ring or loss of magnesium, is described. The appended dihydroflavin was shown to
      quench the fluorescence of protochlorophyllide. In contrast, a
      dihydronicotinamide moiety was unable to effect fluorescence quenching. the
      relevance of these findings to a possible mechanism of action of the enzyme
      protochlorophyllide reductase is discussed.

PMID- 8577862
TI  - Glutathione isopropyl ester reduces UVB-induced skin damage in hairless mice.
AB  - The protective effect of administration of glutathione (GSH) isopropyl ester on
      photodamage, such as lipid peroxidation, inflammation and tumorigenesis induced
      by UV exposure (290-400 nm, max. 312 nm), was investigated using hairless mice.
      Pretreatment with 20 mg/kg GSH isopropyl ester prevented the increases of
      thiobarbituric acid-reactive substance (TBARS) formation in skin and serum sialic
      acid, indices of lipid peroxidation and inflammatory reaction, respectively,
      which were caused by a single dose (15 kJ/m2) of UV irradiation. The level of
      epidermal GSH in skins of the GSH ester-treated mice was maintained within normal
      limits. When mice were exposed to UV at a dose of 2 kJ/m2, three times weekly,
      skin tumors developed in all of them after 25 weeks. The formation of skin tumors
      was significantly inhibited by administration of 10 mg/kg GSH ester prior to each
      UV irradiation for 25 weeks. Moreover, the increases of cutaneous TBARS and serum
      sialic acid in the tumor-bearing mice were also prevented by continuous
      pretreatment with GSH ester. Even after 24 weeks, the epidermal GSH content of
      the pretreated mice was mostly retained compared to nonirradiated mice. However,
      administration of GSH prior to acute or chronic UV irradiation had no effect on
      the UV-induced damage. The present results suggest that the protection from
      photodamage afforded by pretreatment with GSH ester is due to maintenance of a
      normal GSH level.

PMID- 8577863
TI  - Flow cytometric technique for quantitating cytotoxic response to photodynamic
      therapy.
AB  - A simple flow cytometric technique for rapid measurement of multilog cytotoxic
      responses to photosensitization of cellular systems is described. This technique
      is particularly useful for cell lines with a low colony-forming efficiency, for
      which a nonclonogenic assay is required. The assay separates cell-sized objects
      from cellular debris by gating on forward scatter versus side scatter, identifies
      viable cells by positive calcein AM and negative ethidium homodimer-1 staining
      and measures cell concentration relative to an internal standard of polystyrene
      beads. Large numbers of cells can be analyzed rapidly. Two patient-derived small
      cell lung cancer cell lines, NCI-H209 and SV-E, were used to test the technique.
      Photordiation survival curves of the response of these cell lines to 5
      aminolevulinic acid-induced protoprophyrin IX photosensitization correlated with
      the extent of photosensitizer accumulation. There was good agreement between the
      results obtained using the tritiated thymidine incorporation assay and the flow
      cytometric cytotoxicity assay. The technique can be used to measure cytotoxic
      responses to photosensitization of cell lines regardless of their plating
      efficiencies.

PMID- 8577864
TI  - Ultraviolet B radiation increases hairless mouse mast cells in a dose-dependent
      manner and alters distribution of UV-induced mast cell growth factor.
AB  - In studies of the effects of chronic UVB irradiation on dermal connective tissue
      in the hairless mouse, we observed that the number and size of mast cells was
      increased. Because mast cells are known to be associated with connective tissue
      remodeling, we examined and quantified the effect of increasing UVB (290-320 nm)
      doses on this cell. Groups of mice were exposed to filtered FS-40 Westinghouse
      lamps (290-400 nm: peak irradiance 313 nm) for 1-5 minimal erythema doses (MED)
      thrice weekly for 10 weeks. Appropriate controls were included. Biopsies,
      processed for light microscopy, were stained with toluidine blue. Mast cells were
      counted in 15 high-magnification fields per specimen with upper and lower dermis
      scored separately. Significant increases in large densely granular mast cells
      occurred at 2 MED in the lower dermis, in association with a UVB-exacerbated
      granulomatous reaction. In the upper dermis, mast cells were significantly
      increased with 3 MED. These findings suggest that mast cells may play a dual role
      in UV-irradiated skin with those in the lower dermis related to inflammation
      processes and those in the upper dermis involved in connective tissue modeling.
      To gain understanding of the mechanism of mast cell recruitment and maturation,
      we examined the effect of UVB on mast cell growth factor expression. This was
      enhanced in the epidermis by UVB, with a shift from cytoplasmic staining to
      membrane-associated or intercellular staining at 2 MED and higher. Dermal
      dendritic and mononuclear cells also showed increased reactivity.

PMID- 8577865
TI  - Tumor oxygenation changes post-photodynamic therapy.
AB  - Tumor oxygenation after a photodynamic therapy (PDT) treatment is a critical
      factor for understanding the posttreatment metabolic pathway of the tumor. It
      also provides important information for designing combination therapy of PDT and
      other oxygen-dependent anticancer modalities. In this study, mammary carcinoma in
      flank and hind leg of C3H mice were subjected to PDT at either subcurative or
      curative level (12.5 mg/kg Photofrin; 200 or 600 J/cm2, respectively). The before
      and post-PDT tumor oxygenation was measured with an oxygen-sensitive
      microelectrode. The data revealed that tumor oxygenation at the time of PDT has a
      profound effect on posttreatment tumor oxygenation, which may largely be due to
      an interplay between direct PDT cytotoxicity and PDT damage to the tumor
      microvasculature. Transient reoxygenation occurred after PDT, which may provide a
      window for improved combination therapy for other oxygen-dependent modalities.

PMID- 8577866
TI  - Effect of delivery system on the pharmacokinetics and tissue distribution of
      bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC), a
      photosensitizer for tumor therapy.
AB  - Bis(di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) is a
      representative of a group of naphthalocyanine derivatives with spectral and
      photophysical properties that make them attractive candidates for photodynamic
      therapy (PDT). Tissue distributions were studied in tumor-bearing rats as a
      function of delivery system and time following administration. The tumor model
      was an N-(4-[5-nitro-2-furyl]-2-thiazolyl) formamide (FANFT)-induced urothelial
      cell carcinoma transplanted into one hind leg of male Fischer 344 rats; isoBOSINC
      was delivered to the rats by intravenous injection of 0.50 mg/kg of body weight
      as a suspension either in 10% Tween 80 in saline (Tween) or 10% (Cremophor EL +
      propylene glycol) in saline (Cremophor). The isoBOSINC was isolated from several
      tissues and organs, as well as tumors and peritumoral muscles and skin.
      Quantitation was by a high-performance liquid chromatographic technique with
      detection that utilizes the native fluorescence of the naphthalocyanine
      derivative. Independent of the delivery system, the dye was retained in tumors at
      higher concentrations than in normal tissues, except for spleen and liver. The
      isoBOSINC retention in tumors was high and was vehicle dependent. For Tween, the
      maximal ratio of dye in tumor versus peritumoral muscle occurred 12 h after
      injection; for Cremophor, the maximal ratio occurred later, 336 h postinjection.
      When the drug was delivered in Tween, isoBOSINC in serum showed two compartment
      kinetics: half-lives of about 2 and 11 h were found for the distribution and the
      elimination phases, respectively. When Cremophor was the vehicle, the elimination
      half-life was about 20 h, and one compartment kinetics was observed. The latter
      findings may explain the generally higher levels of the dye attained by the
      tissues at later times with Cremophor as the vehicle. An interesting exception
      was that after 7 and 14 days postinjection in Tween, the levels of dye found in
      testes were six- to seven-fold higher than those found after Cremophor delivery.
      Levels of dye were very low or not detectable in the brain. Optimal parameters
      for PDT of tumors with this novel photosensitizer are clearly time- and vehicle
      dependent, and future PDT studies will need to incorporate these modulators.

PMID- 8577867
TI  - Role of Fapy glycosylase and UvrABC excinuclease in the repair of UVA (320-400
      nm)-mediated DNA damage in Escherichia coli.
AB  - In contrast to the damage caused by far-UV, the damage caused by UVA (320-400 nm)
      is largely oxygen dependent, suggesting near-UV-mediated DNA damage involves
      reactive oxygen species. The DNA repair enzymes that recognize oxidized bases
      may, therefore, be an important part of the cell's near-UV defense repertoire. To
      evaluate the relative importance of Fpg (Fapy) glycosylase (an enzyme known to
      remove oxidized bases) and the DNA damage-inducible UvrABC excinuclease in
      recovery from near-UV-induced stress, we have constructed fpg- and uvrA-
      derivatives of Escherichia coli and tested the response (survival) of these
      strains to both UVA and far-UV radiation. Relative to control strains, the fpg-
      derivatives were found to be consistently more sensitive to the lethal effects of
      UVA, but not far-UV radiation. In contrast, uvrA- mutants were more sensitive
      than control strains to both UVA and far-UV radiation. Thymine dimers, known to
      be produced by far-UV and corrected by UvrABC, were not generated by the UVA
      fluences used in this study, suggesting that some other UVA-induced lesion(s) is
      recognized and repaired by this excinuclease.

PMID- 8577868
TI  - Experimental correspondence between spore dosimetry and spectral photometry of
      solar ultraviolet radiation.
AB  - The biologically effective dose of solar UV radiation was estimated from the
      inactivation of UV-sensitive Bacillus subtilis spores. Two types of independent
      measurements were carried out concurrently at the Aerological Observatory in
      Tsukuba: one was the direct measurement of colony-forming survival that provided
      the inactivation dose per minute (ID/min) and the other was the measurement of
      the spectral irradiance by a Brewer spectrophotometer. To obtain the effective
      spectrum, the irradiance for each 1 nm wavelenght interval from 290 to 400 nm was
      multiplied with the efficiency for inactivation derived from the inactivation
      action spectrum of identically prepared spore samples. Integration of the
      effective spectrum provided the estimate for ID/min. The observed values of
      ID/min were closely concordant with the calculated values for the data obtained
      in four afternoons in 1993. The average ratio (+/- SD) between them was 1.24 (+/-
      0.16) for 14 data points showing high inactivation rates (> 0.05 ID/min).
      Considering difficulties in the absolute dosimetry of UV radiation, the
      concordance was satisfactory and improved credibility of the two types of
      monitoring systems of biologically effective dose of solar UV radiation.

PMID- 8577869
TI  - UV-induced changes in cell cycle and gene expression within rabbit lens
      epithelial cells.
AB  - Damage to lens epithelial cells is a probable initiation process in cataract
      formation mediated by UV radiation. In these experiments, we investigated the
      effects of exposure to 254 nm radiation on cell cycle progression and gene
      expression in the rabbit lens epithelial cell line N/N1003A. The RNA was
      harvested at various times following exposure to UV (254 nm) radiation and
      analyzed by dot-blot and northern blot hybridizations. These results revealed
      that during the first 6 h following exposure of the cells to UV, there was,
      associated with decreasing dose, a decrease in accumulation of transcripts
      specific for histones H3 and H4 and an increase in the mRNA encoding protein
      kinase C and beta- and gamma-actin. Using flow cytometry, we detected an
      accumulation of cells in G1/S phase of the cell cycle 1 h following exposure to
      254 nm radiation. The observed changes in gene expression, especially the
      decreased accumulation of histone transcripts reported here, may play a role in
      UV-induced inhibition of cell cycle progression.

PMID- 8577870
TI  - Discrimination of ovarian steroids by rats.
AB  - Rats' ability to discriminate their hormonal states was examined by observing the
      effects of ovarian steroids on state-dependent learning using a drug
      discrimination task. A rat's entry into the correct arm (left or right) of a Y
      maze terminated mild foot shock. The arm designated as correct was alternated
      daily, but was consistently paired with a pretrial injection of hormone or
      vehicle. In Experiment 1, ovariectomized rats successfully discriminated
      pretreatment with 4.0 or 8.0 mg/kg progesterone vs. the oil vehicle but not 2.0
      or 0.5 mg/kg progesterone vs. oil, or the daily alternation schedule alone (oil
      vs. oil). In Experiment 2a, ovariectomized rats correctly discriminated
      pretreatment with progesterone (4 mg/kg) vs. oil or dihydroprogesterone (4 mg/kg)
      vs. oil, and the results of Experiment 2b, appear consistent with the possibility
      that the rats discriminated pretreatment with progesterone vs.
      dihydroprogesterone. In Experiment 3a, ovariectomized rats discriminated on the
      basis of progesterone (4.0 mg/kg) vs. oil, estrogen (6.4 micrograms/kg estradiol
      benzoate) vs. oil, and estrogen vs. progesterone. In Experiment 3b, the rats were
      adrenalectomized, and the procedure from Experiment 3a repeated. The removal of
      the adrenal glands failed to abolish hormonal discriminations, suggesting that
      the effect is not adrenally mediated. The results of these studies show that rats
      can discriminate relatively low doses of ovarian steroids.

PMID- 8577871
TI  - Spatial learning ability of rats following acute exposure to alcohol during early
      postnatal life.
AB  - Previous research has indicated that the developing brain is vulnerable to the
      effects of alcohol exposure. Most of this research has used an experimental
      design in which animals where chronically subjected to alcohol for a lengthy
      period of time during gestation and/or the preweaning period. Recent evidence has
      indicated that the morphology of the brain and the subsequent behaviour of the
      animal may also be susceptible to alcohol administered for a short duration
      during specified periods of development. Wistar rats were exposed to 7.5 g/kg
      body weight of ethanol administered as a 10% solution via an intragastric cannula
      over an 8 h period either on the 5th (PND5) or the 10th (PND10) postnatal day of
      age. Gastrostomy controls received a 5% sucrose solution substituted
      isocalorically for the ethanol. Another set of pups raised by their mother were
      used as 'suckle controls'. All surgical procedures were carried out under
      halothane vapour anaesthesia. After the artificial feeding regimes all pups were
      returned to lactating dams and weaned at 21 days of age. The spatial learning
      ability of these rats was tested in the Morris water maze when they were between
      41-54 days of age. This task requires the rats to swim in a pool containing water
      made opaque and locate and climb onto a submerged platform. The time taken to
      accomplish this is known as the "escape latency." Each rat was subjected to 24
      trials over three days and a further trial on each of days 4 and 11 of the test
      period. Statistical analysis of the escape latency data revealed that both the
      PND5 and PND10 ethanol treated groups had significant deficits in their spatial
      learning ability compared with the control groups. However, there was no
      significant difference in the degree of impairment between the PND5 and PND10
      rats. It is concluded that even short periods of alcohol exposure during brain
      development can cause lasting impairment of spatial learning behaviour in rats.

PMID- 8577872
TI  - Effects of physiological changes of serum glucose on the pattern-VEP of healthy
      volunteers.
AB  - The correlation between amplitude and latencies of the pattern-reversal VEP (1.7
      3.6 50% contrast) and the serum glucose was studied in six healthy, male
      volunteers (21-26 yr.; mean: 23.2 +/- 1.6 yr.). Pattern-VEP and serum glucose
      were obtained at 2-h intervals during a 8-h experimental session. The effect of
      spatial frequency on VEP (increased latencies and amplitude with increasing
      spatial frequency) was removed statistically by computing the residuals from the
      nonlinear regression function vs. the spatial frequency. The residuals were then
      processed as stimulus-independent variables. At glucose serum concentrations
      within the physiological range of variability (55-103 mg/dl), the P100 latency
      increased (p < 0.04) with increasing serum glucose, with a 6.9% estimated latency
      difference between lower and higher glucose concentrations. This correlation
      depends mostly on the association of shorter and longer P100 latencies with
      glucose concentration values in the lower and upper portions of the normal
      concentration range respectively, but accounts for about 4% of the overall
      variance and may be accidental (therefore a potential bias in otherwise
      controlled VEP studies) or suggest functional relationships between glucose
      availability and vision.

PMID- 8577873
TI  - Intestine fullness influences feeding behaviour and crop filling in the domestic
      turkey.
AB  - Image-intensification radiology showed that artificial introduction of food
      slurry into the intestines of 6-12 wk-old turkey hens significantly increased the
      proportion of boli entering the crop during an evening meal, hence decreasing the
      proportion of boli travelling directly to the gizzard. Since bolus movement is
      directed by esophageal motility, esophageal motility may be partially mediated by
      stretch or chemoreceptors in the distal duodenum. Increased crop filling during
      afternoon meals lends support to the widely held belief that the crop increases
      gut storage capacity and helps "tide birds over" the nightly fast. Artificial
      filling of the distal duodenum paradoxically increased food intake in birds
      observed by radiology while eating a single meal (morning and evening), and in
      birds observed by eye over a 3 h period in the morning. This phenomenon is
      similar to that previously reported for rabbits and domestic chicken. Conversely,
      duodenal filing reduced food intake over a full day (11 h), more than
      compensating for the introduced food. Rapid filling of the small intestine
      (within 25 min. of the start of the meal) suggests a modification of the function
      of the domestic turkey duodenum to serve as a "mixing chamber," possibly
      enhancing digestive efficiency. The ways in which this modification affects
      digestion and absorption in the duodenum warrant investigation.

PMID- 8577874
TI  - Simulated uterine contractions facilitate fetal and newborn respiratory behavior
      in rats.
AB  - We tested the hypothesis that sensory and nonsensory factors associated with
      birth stimulate respiratory behavior in the fetal and newborn rat. Late gestation
      (Day 21) rat fetuses were externalized from the uterus with intact umbilical
      connections to the dam and exposed to stimuli normally associated with labor and
      delivery. Onset and maintenance of respiratory movements were monitored. In the
      first experiment, rat fetuses were exposed to either: (i) simulated uterine
      contractions; (ii) cooling (26 degrees C); (iii) umbilical cord occlusion; or
      (iv) air heated to intrauterine temperature (37.5 degrees C). Subjects were
      videotaped for 1 h, and respiratory movements counted during tape review. Fetuses
      in each group showed some respiratory behavior although compression significantly
      elevated respiratory rate compared to other experimental conditions. All subjects
      in each group were respiring after 1 h, except for pups that received umbilical
      cord occlusion. The 100% attrition rate of the cord occlusion-alone group was
      reversed by combining cord occlusion with compression, or with compression and
      cooling, but not by combining cord occlusion with cooling. Simulated birth pups
      (i.e., those exposed to compression, cooling and umbilical cord occlusion) and
      normal, vaginally delivered pups breathed at identical rates and showed a similar
      pattern of postpartum breathing. These results suggest that mechanical
      stimulation of the fetus associated with uterine contractions plays a critical
      role in the maintenance of continuous respiration at birth. Possible mechanisms
      for the facilitative effects of compression on perinatal breathing are discussed.

PMID- 8577875
TI  - Sequential hypothesis of sleep function. V. Lengthening of post-trial SS episodes
      in reminiscent rats.
AB  - Rats failing to learn a two-way active avoidance task during the training session
      were tested for performance the following day. One group of rats maintained its
      low level of avoidances (non improving or NI rats), while the remaining rats
      dramatically improved their avoidance score (improving or I rats). EEG recording
      during the posttrial period demonstrated significant variations in the sleep
      structure of I rats, in comparison with NI rats. The main change consisted in an
      increase in the average duration of the episodes of slow wave sleep followed by
      wakefulness or by paradoxical sleep. These variations occurred in the third hour
      of the posttrial period, while an increment in the amount of PS was observed in
      the sixth hour. In I rats, but not in NI rats, comparable variations emerged from
      the comparison of baseline sleep (determined the day before training) with
      posttrial sleep. The data are in agreement with the main postulate of the
      sequential hypothesis of sleep function which attributes a primary role to slow
      wave sleep in the processing of newly acquired memories.

PMID- 8577876
TI  - Spatial navigation of staggerer and normal mice during juvenile and adult stages.
AB  - Staggerer mutant mice were compared to normal mice of two different ages (2-6 mo)
      in two tasks requiring navigational skills in a circular maze visible platform
      condition and a T-maze. Staggerer mutants had higher latencies than normal mice
      in both tests. The performance of normal mice worsened with age for both tests.
      The aging factor interacted with the genotype factor only in the circular maze,
      where the mutant-nonmutant differential was wider among juvenile animals. In
      neither task was there evidence of a more pronounced impairment with aging in
      staggerer mutants. It remains to be determined in this mutant at more advanced
      stages of aging or in other models of chronic neural disease whether early
      neuropathology accelerates brain aging.

PMID- 8577877
TI  - Urine marking and maternal aggression of wild female mice in relation to
      anogenital distance at birth.
AB  - A series of experiments were conducted with wild house mice to verify the effect
      of intrauterine position on females' anogenital distance at birth (AGD) and to
      examine the relationships between a female's AGD, used as a bioassay of androgen
      exposure during fetal life, and her social behavior and reproductive success in
      adulthood. Experiment 1 showed that cesarean-delivered females that developed in
      utero between two males (2 M females) have significantly longer AGD's than
      females positioned between two females (0 M females). We then categorized
      naturally delivered females shortly after birth as having a long, medium or short
      AGD. In adulthood, these females were tested for their behavior towards
      unfamiliar pups, their rate of urine-marking in response to a variety of social
      stimuli, postpartum aggression and success in protecting their litters in
      response to male and female intruders. Adult females with different AGD's at
      birth did not differ either in their behavior toward pups or in their rate of
      urine marking. Conversely, males housed across a wire mesh partition from a long
      AGD female deposited a higher number of urine marks than those exposed to a short
      AGD female. When tested after delivering a litter, long-AGD females displayed
      more tail-rattling (a component of agonistic behavior) towards intruders of both
      sexes in comparison to short-AGD females. These results are consistent with the
      hypothesis that females with a long AGD are exposed to higher levels of
      Testosterone during fetal life than females with a short AGD. Although not
      related to AGD, other measures of maternal aggression were affected by postpartum
      day, sex of intruders and a female's infanticidal potential while a virgin.

PMID- 8577878
TI  - Analysis of the possible altering function of the septal organ in rats: a
      lesional and behavioral study.
AB  - The septal olfactory organ is a small patch of sensory epithelium located on the
      septal wall at the entry of the nasopharynx. There is a general consensus that by
      sampling olfactory stimuli during periods of rest, this organ may have an
      alerting function. To verify this hypothesis, we have lesioned by
      electrocoagulation the septal organ of male rats and recorded by polygraphy their
      awakening reaction in response to biologically meaningful (trimethyl-thiazoline,
      dimethyl sulfite, food) and meaningless (geraniol, eucalyptol) odorants. The
      awakening reactions of both lesioned and intact rats in response to these
      odorants were studied according to 3 parameters, frequency, latency and duration
      of awakening, and were analyzed using three-way analyses of variance. Data show
      that no significant difference in the awakening reactions was observed between
      control and lesioned animals. In all cases, the biologically meaningful odors
      presented the highest awakening influence. In addition, two of these odors
      (trimethyl-thiazoline and dimethyl sulfite) elicited a later habituation in
      comparison to biologically meaningless odors. From our results, it could be
      inferred that the hypothesis regarding an alerting function that would be
      specific to the septal organ, appears no longer current.

PMID- 8577879
TI  - Monoaminergic influences on temporal patterning of sexual behavior in male rats.
AB  - We evaluated the effects of the serotonin (5-HT) presynaptic uptake blocker
      fluoxetine (FLX) and the dopamine (DA)/noradrenaline (NE) releaser amantadine
      (AMA), separately and in combination, on the temporal patterning of male rat
      sexual behavior. FLX alone increased intermount-bout intervals, time-outs,
      grooming time, ejaculation latency, number of mounts per mount bout, and number
      of mount bouts per ejaculation. AMA alone had the opposite effect on these
      measures. Additionally, AMA, when given in combination with FLX, completely
      reversed the FLX-induced deficits in copulatory behavior. We interpret our
      results as suggesting an interaction between 5-HT and catecholamines in the
      temporal patterning of male rat copulatory behavior.

PMID- 8577880
TI  - Benzodiazepines and palatability: taste reactivity in normal ingestion.
AB  - The taste reactivity (TR) test was devised as a method to obtain behavioural data
      in response to gustatory stimuli in neurologically impaired rats, incapable of
      voluntary feeding. Sapid solutions were infused through surgically implanted
      intraoral cannulae. Facial and motor responses corresponded well to known hedonic
      and aversive properties of tastes (e.g., sweet, bitter). TR testing has since
      proved effective as an adjunct to intake-based methods, in the psychopharmacology
      of ingestion in the normal rat. We developed a nonsurgical modification of the TR
      test, in which intact rats sampled stimuli voluntarily. The benzodiazepine
      receptor agonist midazolam (3.0 mg/kg, IP) was administered to rats first trained
      to consume a sweet 3% sucrose solution, and later tested with access to a bitter
      0.01% quinine solution. Response were videotaped, and TR measures were scored
      during periods of noningestion using a frame-by-frame playback. Treatment
      increased ingestion and facilitated ingestive responses in accordance with
      published data for cannulated rats. Results support a two-component view of
      response palatability, in which treatment alters feeding motivation, increasing
      positive palatability and facilitating ingestion of both palatable and
      unpalatable stimuli.

PMID- 8577881
TI  - Fluid balance in rats of three different strains after inhibition of histamine
      catabolism.
AB  - The effect of metoprine, an inhibitor of histamine (HA) catabolism, on fluid
      balance was studied in Wistar (W) and Long-Evans (LE) rats. AVP deficient
      Brattleboro (BB) rats were used to evaluate which phenomena were AVP-related. W
      and LE rats were quite different: LE rats were "dry" rats, they drank less, had
      higher plasma AVP, smaller urine volume and excreted more AVP, and responded less
      to salt loading and water deprivation. Furthermore, LE and W rats responded
      differently to metoprine. When water was provided as drinking fluid, metoprine
      increased water intake and urine flow in W rats, but these changes were not
      significant in LE rats. In contrast, when the rats drank saline, urine output and
      saline consumption were similarly decreased in LE and W rats. Although no
      metoprine-induced changes in plasma AVP were observed, urinary excretion of AVP
      per 24 h was reduced in metoprine treated rats. Inhibition of HA catabolism by
      metoprine caused only minor changes in fluid balance of AVP deficient BB rats.
      The results show that significant differences in fluid balance can exist between
      rat strains and that increased availability of HA after IP given metoprine
      strongly affects body fluids in normal rats, especially those of the W strain.
      The results provide further support to the involvement of HA in the regulation of
      fluid balance, but to obtain a more complete picture, other factors, such as
      atrial natriuretic peptide, should be studied.

PMID- 8577882
TI  - Maximal sprint speeds and muscle fiber composition of wild and laboratory house
      mice.
AB  - We compared males from four groups of house mice (Mus domesticus), all bred and
      raised under common conditions in the laboratory: randombred Hsd:ICR; a wild
      population from Wisconsin; hybrids from lab dams; hybrids from wild dams. Wild
      mice were much faster sprinters (maximal forced sprint speeds over 1.0 m ranged
      from 2.38 to 3.34 m/s) than were lab mice (range = 0.89-1.68 m/s). Hybrids
      exhibited intermediate speeds (range = 1.54-2.70 m/s) and body masses, indicating
      largely additive inheritance. Type-specific mean muscle fiber cross-sectional
      areas of the gastrocnemius muscle did not differ significantly among groups.
      Percentage cross-sectional areas occupied by each of the three identified fiber
      types also did not differ significantly among groups, nor did they covary with
      body mass. For their body mass, however, lab mice had smaller gastrocnemius
      muscles than did wild and hybrid mice, which had muscles of similar size.
      Although we cannot rule out the possibility that smaller gastrocnemius muscles or
      slight differences in fiber composition account for the lower sprint speeds of
      the lab mice, we suggest that differences in unmeasured physiological, behavioral
      or motivational factors are probably the primary cause. This interpretation is
      supported by a lack of correlation between individual differences in sprint speed
      and either relative gastrocnemius muscle mass or muscle fiber type composition.

PMID- 8577883
TI  - Hyperthermia following MDMA administration in rats: effects of ambient
      temperature, water consumption, and chronic dosing.
AB  - In two experiments it was found that the hyperthermia which follows MDMA
      ("Ecstasy") results from an interaction of direct pharmacological effect of the
      drug and the prevailing environmental conditions in which it is administered. In
      Experiment 1, rats given fixed doses of either 2.5, 5.0 or 7.5 mg/kg MDMA or
      saline were injected on different days at ambient temperatures (Ta's) of 11, 24,
      and 30 degrees C. At each Ta drinking water was freely available following dosing
      on one session and temporarily unavailable on a second. The hyperthermic and
      hyperkinetic responses were monitored using remote biotelemetry. Experiment 2
      used a between-subject design in which each group of rats received a standard 7.5
      mg/kg dose of MDMA administered at only one of the three levels of Ta(24 degrees
      C) and at only one level of the water-availability factor. Dosing in some groups
      was continued for a further 13 days to test for tolerance or sensitization
      effects. Ambient temperature significantly affected the magnitude of the
      hyperthermia but not the hyperkinesis. Water deprivation during the drugged
      period significantly augmented the hyperthermia, but only in the high Ta (30
      degrees C.) condition. Chronic dosing produced sensitization of both hyperthermic
      and hyperkinetic responses. The findings indicate that ambient temperature, water
      consumption and frequency of drug use affect the hyperthermia which follows MDMA
      administration.

PMID- 8577884
TI  - Menstrual synchrony: only in roommates who are close friends?
AB  - This study examined menstrual synchrony among roommates residing in 20 university
      housing units. Menstrual synchrony was examined for roommates who were close
      friends and roommates who were not close friends, and by housing unit. The impact
      of personality, social-interaction and menstrual-related factors was also
      studied. To avoid limitations found in previous studies, (i) data were collected
      prospectively and (ii) over the entire academic year; (iii) high participation
      rate was obtained (86%); and (iv) women who used oral contraceptives were
      excluded. Menstrual synchrony was found among roommates who were close friends.
      Synchrony was not found for roommates who were not close friends, nor by housing
      units. The phenomenon of menstrual synchrony may more likely occur among close
      friends and women with intensive social contact than under the conditions common
      to university dormitories.

PMID- 8577885
TI  - Behavioral responses to low doses of cocaine are affected by genetics and
      experimental history.
AB  - We recently conducted a set of two experiments to investigate the possible co
      operation between genetics and exposure to novelty on the putative locomotor
      inhibiting effects of low doses of cocaine in male and female C57BL/6 and DBA/2
      mice. Experiment one examined the effects of three low doses of cocaine (0.1,
      0.5, and 1.0 mg/kg) on locomotion, exploration, stereotypy and wall-seeking in an
      automated activity monitor. Testing occurred on two consecutive days, with
      subjects receiving an IP injection of saline on day one, and one dose of cocaine
      on day 2 (S-C). Immediately following injection, subjects were placed into
      automated activity monitors, where four behaviors were recorded; total distance,
      nosepokes, stereotypy and margin time. Using this S-C injection regimen, we found
      significant decreases in measures of total distance and stereotypy when compared
      to saline in both male and female C57 mice. Experiment two was designed to
      determine if the observed decrease in locomotor activity was the result of low
      dose cocaine or pre-exposure to the test procedure and apparatus. All conditions
      and procedures were identical to those in experiment one, with the exception of
      the injection regimen. In this experiment, we injected all subjects IP with 0.1
      mg/kg cocaine on day one, followed by saline on day two (C-S). Additionally, a
      group of subjects receiving saline on both days (S-S) served as the control. In
      contrast to experiment one results, cocaine produced locomotor activation.
      Furthermore, significant sex and strain differences were found in both
      experiments. The results of our experiments suggest that the behavioral effects
      of low doses of cocaine are markedly influenced by both the genetic constitution
      of the experimental animal and by familiarity with the test apparatus.

PMID- 8577886
TI  - Effect of amphetamine on human macronutrient intake.
AB  - Six male subjects participated in a 15-day residential study examining the
      effects of amphetamine on macronutrient intake. During the first 11 days,
      carbohydrate intake was manipulated by providing lunch meals high (155 g) or low
      (25 g) in carbohydrate. Subjects received oral d-amphetamine (5, 10 mg/70 kg,
      BID) or placebo. Total daily caloric intake was similar under both lunch
      conditions (approximately 3400/Kcal), but carbohydrate contributed more energy
      under the high-carbohydrate condition. Both doses of amphetamine decreased total
      caloric intake to approximately 2600 Kcal, by decreasing the number of eating
      bouts, without affecting macronutrient selection. During the last four days
      subjects received a higher daily dose of amphetamine (30 mg/70 kg in four doses)
      or placebo, and were allowed to self-select lunch. Although 30 mg amphetamine
      decreased intake of all macronutrients, the relative contribution of carbohydrate
      to total caloric intake was increased from 54% to 62%, while the contribution of
      fat was decreased from 32% to 26% and the contribution of protein was decreased
      from 14% to 12%. Thus, at a high dose, amphetamine altered the relative
      contribution of specific macronutrients to total caloric intake.

PMID- 8577887
TI  - Locomotor and passive avoidance deficits following occlusion of the middle
      cerebral artery.
AB  - The characterization of sensory, motor and cognitive dysfunctions following
      occlusion of the middle cerebral artery (MCA) is prerequisite to investigations
      of treatment intervention in animal models of ischemia. Different strategies are
      used to induce ischemia, but the focal, transient occlusion of the MCA has been
      reported to result in neuropathology most similar to that seen in clinical
      cerebral ischemia. If the MCA occlusion technique results in a stroke animal
      model, then the behavioral impairments inherent in stroke should be manifested in
      this model. The present study provides a further characterization of behavioral
      alterations associated with MCA occlusion. Sprague-Dawley rats underwent temporal
      occlusion of the right MCA, and at 1 mo and 2 mo postischemia, were subsequently
      tested in passive avoidance behavior, motor coordination, asymmetrical motor
      behavior, neurological functioning, nocturnal spontaneous and amphetamine-induced
      locomotor activity, and haloperidol-induced catalepsy. Results revealed that
      ischemic rats showed long-term impairments in sensory, motor and cognitive
      functions. The discrepancy with other studies reporting temporal MCA-induced
      behavioral deficits may be due to techniques used to induce ischemia and
      consequent CNS damage, differences in time period of testing (i.e., immediate vs.
      later postischemia, nighttime vs. daytime), number of test-retests over the
      course of the experiment, and age of the animals. The mechanism involved in the
      MCA-induced behavioral changes may be represented by loss of dopamine receptors
      on striatal neurons. Histological analysis revealed damage limited to the lateral
      aspect of the striatum. These behavioral and anatomical data support MCA
      occlusion as a model of ischemia, and elucidate important factors that should be
      controlled for in characterizing the MCA-induced neuropathological alterations.

PMID- 8577888
TI  - Effects of beta adrenergic receptor blockade on hemodynamic changes associated
      with obstructive sleep apnea.
AB  - To study the effects of airway obstruction (AWO) and arousal on coronary blood
      flow, mean arterial pressure (MAP) and heart rate (HR), pigs were chronically
      instrumented with arterial catheters, Doppler flow probes on the left circumflex
      coronary artery, and electrodes for determination of sleep stages. A modified
      balloon catheter was placed in the trachea to obstruct the upper airway during
      sleep. Following control studies, the role of beta adrenergic receptors in
      hemodynamic responses to AWO was assessed by administering propranolol, a beta
      adrenoreceptor blocking agent. In control studies, during nonrapid eye movement
      sleep (NREM), MAP was 85 +/- 2 mmHg before AWO and increased by 8 +/- 2 mmHg upon
      arousal. Mean arterial pressure was lower during rapid eye movement (REM) sleep
      (64 +/- 2 mmHg) and the increase upon arousal was threefold greater (22 +/- 2
      mmHg). Heart rate was similar in both sleep stages (NREM 123 +/- 5 bpm; REM 125
      +/- 6 bpm) and increased significantly upon arousal (NREM, 11 +/- 2 bpm; REM, 18
      +/- 3 bpm increase). Coronary blood flow was similar during both stages (NREM 44
      +/- 5 ml/min; REM 44 +/- 6 ml/min) and increased by 13% (NREM) and 22% (REM)
      during arousal. Coronary vascular resistance increased significantly by 17%
      during arousal from AWO during REM sleep. All changes were significant at p <
      0.05. Following beta adrenergic receptor blockade studies using propranolol,
      baseline HR was reduced in NREM sleep and HR and coronary blood flow increases
      during arousal from apnea were eliminated. Adrenoreceptor blockade studies
      suggest that these effects were mediated by the beta adrenergic component of the
      sympathetic nervous system.

PMID- 8577889
TI  - Maternal ingestion of ortho-aminoacetophenone during gestation affects intake by
      offspring.
AB  - Ingested flavor chemicals cross the placental barrier and occur in the fetal
      blood and amniotic fluid. This occurrence is detectable by the fetus, and can
      influence post parturition feeding. In the present experiment, pregnant mice were
      offered either 0.1% ortho-aminoacetophenone emulsions (OAP) or water throughout
      gestation. OAP is normally avoided by mice, apparently on the basis of
      chemosensory characteristics. Subsequently, offspring were offered 0.5%, 0.25%,
      or 0.1% OAP in one-bottle tests at 26 or 88 days of age. Offspring of mothers
      given OAP drank greater amounts of OAP than did offspring of mothers given water.
      Enhanced acceptance of OAP was not detected in mice exposed to 0.1% OAP as adults
      for a duration similar to that given during gestation. We conclude that fetal
      experiences with OAP lowered sensitivity and/or raised tolerance for the
      compound.

PMID- 8577890
TI  - Decreased dominance in a limited access test but normal maternal behavior in
      micrencephalic rats.
AB  - Micrencephalic offspring produced by gestational treatment with the antimitotic
      compound/methylazoxymethanol acetate (MAM) are remarkable for substantial
      preservation of function concurrent with severe neural stunting. Altered
      behaviors in these micrencephalics, including light shyness and response
      perseveration, are similar to those produced by frontal cortex lesions.
      Consistent with this, the frontal cortex is one of several regions severely
      stunted by gestational MAM treatment. Because the frontal cortex has been
      implicated in rodent social behavior, maternal behavior in females and dominance
      in both sexes were assessed. Dominance was measured via water competition in 24-h
      water-deprived dyads (1 control and 1 MAM) matched for sex and body weight.
      Micrencephalic rats exhibited shorter drinking time than controls (males: 101 vs.
      219 s, p < 0.001; females: 114 vs. 176 s, p < 0.03), indicating that
      micrencephalics were more submissive. For maternal behavior tests, micrencephalic
      and control females were bred to control males and pup retrieval was measured on
      postnatal days 3-13. Micrencephalic dams were unimpaired in any aspect of pup
      retrieval. Of 8 standard behavior measures used here and previously, access time
      in water competition tests produced the clearest differentiation between control
      and micrencephalic rats. These studies indicate that at least one aspect of
      social dominance in both sexes is severely reduced by MAM treatment while
      maternal behavior remains intact.

PMID- 8577891
TI  - Behavioral and neurochemical changes in folate-deficient mice.
AB  - Weanling mice were fed an amino acid-based diet supplemented with 0 or 11.3 mumol
      folic acid/kg diet for approximately 38 days to study behavior and neurochemistry
      in folate deficiency. After approximately 5 wk, mice fed the unsupplemented diet
      weighted approximately 70% as much those fed the supplemented diet. After 2 wk,
      mice fed the unsupplemented diet consistently discarded (spilled) more food, and
      after approximately 5 wk, they had spilled 3 times more than mice fed the
      supplemented diet. Serum folate, brain folate and brain S-adenosylmethionine of
      mice fed the unsupplemented diet were 4, 53, and 60% as high, respectively, as
      those of mice fed the supplemented diet. Pathologic changes were not evident in
      brain, spinal cord, or skeletal muscle of folate-deficient mice. The hypothalamic
      5-hydroxyindole acetic acid/serotonin ratio and caudate dopamine, homovanillic
      acid, and 3,4-dihydroxyphenylacetic acid concentrations were lower in deficient
      than control mice. Folate-deficient mice develop a behavioral activity, food
      spilling, which may have a neurochemical basis in the serotonin and dopamine
      systems.

PMID- 8577892
TI  - Daily melatonin infusions entrain the locomotor activity of pinealectomized
      lizards.
AB  - Previously, it was shown that the locomotor activity rhythms of pineal-intact
      lizards (Sceloporus occidentalis) could be entrained to a periodicity of 24 h by
      10-micrograms melatonin injections administered every other day at the same time.
      The present study examined the response of the circadian activity rhythm of
      pinealectomized S. occidentalis to daily 12-h infusions of smaller quantities of
      melatonin (0.1 or 5 micrograms melatonin/day). The results show that entrainment
      is achieved by infusion of 0.1 microgram of melatonin/day in pinealectomized
      lizards, as well as by 5 micrograms of melatonin/day in pinealectomized and
      pineal-intact lizards. Serum melatonin levels in pinealectomized lizards
      receiving 0.1 microgram melatonin/day (measured in the middle of the infusion
      period) were comparable to mid-dark levels in intact lizards. These results
      provide further support for the hypothesis that the pineal, via its daily rhythm
      of melatonin secretion, plays an important role in the circadian organization of
      lizards.

PMID- 8577893
TI  - Estradiol concentration and the regulation of locomotor activity.
AB  - We predicted that female prairie voles (Microtus ochrogaster) would not increase
      in locomotor activity during "induced" proestrus. We developed and tested two
      alternative a priori hypotheses to explain this predicted lack of activity. The
      Non-Response Hypothesis in which voles cannot, physiologically, increase activity
      in response to estradiol and, the Threshold Effect Hypothesis in which a minimal
      concentration of estradiol is necessary to achieve estrus, while higher
      concentrations influence other behavioral parameters. The non-response hypothesis
      predicts that hormone concentration will not affect locomotor activity, while the
      threshold effects hypothesis predicts that voles achieve estrus at low
      concentrations, while higher concentrations should trigger increasing locomotor
      activity. Initial results using running wheels indicated that females decreased
      activity during induced proestrus. Radioimmunoassay revealed that induced
      proestrus was achieved at relatively low concentrations of estradiol. Results
      from a dose response experiment allowed for rejection of the nonresponse
      hypothesis and supported the threshold effects hypothesis as females decreased
      activity at low concentrations of estradiol, showed no relative change at
      moderate concentrations, and increased activity at higher concentrations.

PMID- 8577894
TI  - Restoration of olfactory mediated behavior after olfactory bulb deafferentation.
AB  - Transection of olfactory nerve fibers leads to deafferentation of olfactory bulbs
      and a loss of olfactory mediated behavior. Nerve transection studies have shown
      that during recovery, olfactory nerve fibers can reestablish connections with the
      olfactory bulbs. Two groups of experimental animals were studied to determine if
      olfactory mediated behavior returns after recovery. One group (n = 18) received
      bilateral olfactory nerve transection (BTX), while the second group (n = 4)
      received a sham surgical procedure. Performance on odor detection and
      discrimination tasks was measured during recovery periods ranging from 1-120
      days. Return of olfactory mediated behavior was first observed 19 days after
      nerve transection. Performance levels improved with recovery time and by day 40
      animals returned to criterion level (> or = 90% correct response). Sham animals
      maintained a criterion level of performance throughout the recovery period.
      Horseradish peroxidase (HRP) was used to trace reconnection of olfactory nerve
      fibers. The absence of HRP label in the bulbs of animals examined one day after
      BTX, verified the completeness of the nerve transection procedure. After 10 days
      of recovery, a few HRP labeled axons were observed and the amount of HRP in the
      bulb increased with recovery time. The results of this study demonstrate that
      olfactory receptor axons can reestablish functional connections with the
      deafferented olfactory bulb and these connections are sufficient to restore
      olfactory mediated behavior.

PMID- 8577895
TI  - Methotrexate does not interfere with an appetitive Pavlovian conditioning task in
      Sprague-Dawley rats.
AB  - There has been considerable interest in developing an animal model of the
      neuropsychological toxicity of chemotherapeutic agents used in the treatment of
      patients with cancer, especially children, since these agents often cause
      significant, long-term neuropsychological deficits. Yanovski, Packer, Levine,
      Davidson, Micalizzi, D'Angio (13) recently proposed such a model based on their
      finding that methotrexate retarded the formation of aversive Pavlovian excitatory
      associations. The present experiment examined the generality of methotrexate
      induced cognitive impairments by testing rats in Appetitive Pavlovian
      Conditioning tasks and a Conditioned Taste Aversion paradigm. The results of our
      study revealed no impairment following methotrexate exposure on the Appetitive
      Pavlovian tasks or on the Taste Aversion task, relative to two control
      conditions. While there were a number of methodological differences between the
      present experiment and those conducted by Yanovski et al. (13), the present
      results question the robustness and generality of Yanovski's et al. (13) animal
      model.

PMID- 8577896
TI  - Sound does not entrain the motor activity circadian rhythm of rats.
AB  - The effect of sound/silence cycles on the motor activity rhythm of the rat was
      studied. The daily motor activity pattern was studied in two groups of rats of
      both sexes kept first under DD and later under LL. One group (16 rats) was
      subjected to a cycle of sound and silence and the other (8 rats) was used as
      control. The study was performed under two different light regimes, to consider
      the possibility that a weak zeitgeber (such as sound might be), would exert an
      effect on the circadian pacemaker. This effect would depend on the stability of
      the circadian system, which could be modified by the lighting conditions. Results
      show no statistically significant differences between the two groups, neither in
      the motor activity patterns nor in the period of the rhythm. It was concluded
      that sound is not a zeitgeber for the motor activity rhythm of rats.

PMID- 8577897
TI  - Effects of maternal stress on methylmercury-induced developmental toxicity in
      mice.
AB  - The developmental toxicity of combined exposure to maternal restraint stress and
      methylmercury chloride (MMC) was assessed in Swiss mice. On day 10 of gestation,
      four groups of plug-positive female mice were treated (p.o.) with a single dose
      of 12.5 or 25 mg MMC/kg. Immediately after MMC exposure, two of those groups were
      subjected to restraint for 14 hr. Control groups included restrained and
      unrestrained pregnant mice nonexposed to MMC. Combined exposure to 25 mg MMC/kg
      and restraint enhanced MMC-induced maternal toxicity, which included deaths and
      decreased body weight gain and food consumption. The number of nonviable implants
      was also increased significantly following concurrent exposure to MMC (25 mg/kg)
      and restraint, with the percentage of postimplantation loss increased from 64%
      (MMC alone) to 100% (MMC plus restraint). However, the types and incidence of
      internal and skeletal anomalies observed after administration of 12.5 mg MMC/kg
      were not increased by maternal restraint. These results suggest that maternal
      stress would enhance the MMC-induced maternal and embryo/fetal toxicity at doses
      of MMC that are highly toxic to the dams, whereas at doses that are less acutely
      toxic the role of maternal stress would not be significant.

PMID- 8577898
TI  - Ring A reduced progestins potently stimulate estrous behavior in rats:
      paradoxical effect through the progesterone receptor.
AB  - The effect of ring A reductions at C5 and C3 on the capacity of the progesterone
      (P) molecule to stimulate estrous behavior was studied in ovariectomized estrogen
      primed rats (5 micrograms estradiol benzoate, EB, 40 h before progestin
      administration). Dose-response curves (dose range: 0.75-200 micrograms) for the
      lordosis quotient (LQ), lordosis score (LS), and proceptivity were constructed
      for P and all its ring A reduced metabolites: 5 alpha-pregnanedione (alpha DHP),
      5 beta-pregnanedione (beta DHP), 3 alpha,5 alpha-pregnanolone (3 alpha,5 alpha
      Pgl), 3 alpha,5 beta-pregnanolone (3 alpha,5 beta-Pgl), 3 beta,5 alpha
      pregnanolone (3 beta,5 alpha-Pgl), and 3 beta,5 beta-pregnanolone (3 beta,5 beta
      Pgl). Progestins were dissolved in propylene glycol and IV injected through an
      indwelling jugular catheter. Tests for lordosis and proceptivity were made at 5,
      30, and 120 min after progestin injection. Weak, though significant lordosis
      behavior was observed at 5 min following the injection of some of the progestins,
      particularly the pregnanolones. Maximal responses were obtained at 120 min
      postinjection for all progestins. Dose response curves of the LQ, LS, and
      proceptivity were dualistic for alpha DHP and both 3 alpha pregnanolones, smaller
      responses being observed with high doses. Relative potency analysis revealed that
      alpha DHP, 3 alpha,5 beta-Pgl, 3 beta,5 alpha-Pgl, and 3 alpha,5 alpha-Pgl were
      considerably more potent for eliciting lordosis than P (14, 13.7, 9, and 4-fold,
      respectively). The same order of relative potencies was found for both LS and
      proceptivity. 3 beta,5 beta-Pgl and beta DHP were only slightly more potent than
      P (2 and 1.5-fold, respectively). In a second study, the antiprogestin RU486 (5
      mg, SC), injected 60 min before one of four selected progestins (alpha DHP, 3
      alpha,5 alpha-Pgl, 3 alpha,5 beta-Pgl, and 3 beta,5 beta-Pgl), significantly
      inhibited their action on estrous behavior (lordosis and proceptivity) when
      tested at 60 and 120 min postinjection. On the other hand, RU486 failed to
      inhibit early lordotic responses obtained at 5 and 30 min following 3 alpha,5
      alpha-Pgl and 3 alpha,5 beta-Pgl. Similarly RU486 was ineffective in inhibiting
      lordosis in ovariectomized rats treated only with estradiol (3 micrograms of
      EB/day for 7 days). Data suggest that: (i) ring A reduction of the P molecule
      plays an important role in the normal facilitation of estrous behavior in the
      rat; and (ii) ring A reduced progestins provoke this effect by acting, at least
      partially, through the progesterone receptor.

PMID- 8577899
TI  - Contribution of stress and gender to exploratory preferences for familiar versus
      unfamiliar conspecifics.
AB  - An apparatus for measuring the exploratory preferences of rats for familiar and
      unfamiliar conspecifics in a novel environment was designed. The exploratory
      behavior of males and females was compared and contrasted to that elicited in
      response to an acute aversive event. Sprague-Dawley male and female rats were
      exposed to restraint and 60, 1 s, 1 mA tailshocks and returned to their home
      cage. Either 2 or 24 h later, they were placed in a novel environment with a
      familiar cage-mate and an unfamiliar conspecific of the same sex. Relative to
      unstressed controls and females, males stressed 2 h previously decreased the
      exploration of the unfamiliar conspecific, exhibiting a rapid decrease over the
      course of the trial. In response to the stressor, however both sexes, however,
      decreased the exploration of the familiar conspecific, decreased their overall
      activity, and returned preferentially to their starting quadrant. None of these
      stress-induced effects were evident 24 h later upon the first or second exposure
      to the apparatus. Thus, exposure to the stressor transiently increased
      perseveration and decreased activity in males and females, but only decreased the
      exploration of novel conspecifics in males. These results indicate that a number
      of behavioral responses to stressors are conserved across gender, but those
      relating to novelty are more pronounced in males.

PMID- 8577900
TI  - [Problems of psychogeriatrics].
AB  - The author discusses the present state and needs of psychogeriatry in Poland. He
      considers the situation within the period of 33 years, which, in his opinion, has
      not been distinctly improved in spite of growth of old age disorders and various
      psycho-social threats connected with economical difficulties. The author
      discusses shortly the diagnostic criteria as well as the state of research on
      etiopathogenesis and treatment of the Alzheimer's disease.

PMID- 8577902
TI  - [Usefulness of CAMDEX test in the analysis of clinical picture of dementia].
AB  - Mild to moderate dementia fulfilling ICD-10 criteria and with MMSE score below 24
      was analyzed in a sample of 46 randomly chosen elderly people. Selected scales
      derived from Polish version of CAMDEX and its cognitive section (CAMCOG) were
      used for assessment of clinical picture. Psychopathological symptoms, e.g.,
      depression were frequent, especially in female group. According to the results of
      multivariate analyses of CAMCOG subscales, the most frequent symptoms in mild
      dementia were: the impairment of recent memory, abstract thinking, and praxis (p
      < 0.001).

PMID- 8577901
TI  - [Clinical picture of dementia].
AB  - Author presents a review of detailed psychopathological picture of dementia
      syndromes. Apart from memory impairment, a large, number of other symptoms
      regarding personality changes, perception and thought changes as well as
      disturbed behaviour must be taken into account.

PMID- 8577903
TI  - [Social functioning of patients with schizophrenia: a follow-up study].
AB  - The subject of this study was evaluation of social functioning of schizophrenic
      patients after a period of ten to twenty years of follow-up. 70 patients (29 men
      and 41 women) selected from the initial group of 303 patients (181 men and 122
      women), with the diagnosis of schizophrenia were studied. They had been admitted
      for the first time to the Hospital for Mental and Nervous Diseases in Gniezno in
      the years 1975-76. Examinations were carried in household environment (interviews
      with patients and their relatives), based on of a standardized questionnaire. In
      the examination, six realms of social activity were considered: professional
      occupation, home occupation, self independence, participation in family life,
      care for a child, social relations and interests. The level of social functioning
      in the examined group of 70 schizophrenic patients several years after the first
      psychiatric hospitalization has been found satisfactory in 57% patients. Women
      were functioning better, especially in the scope of participation in family life
      and fulfilment of home duties. Better level of social functioning was related to
      lower family history of mental illness, lower degree of invalidization, activity
      attitude towards the illness and positive self evaluation of the state of health,
      advantageous family situation, better fulfilment of social needs and lower family
      burden caused by the patient.

PMID- 8577904
TI  - [Methods of measurement of social adjustment in schizophrenia].
AB  - Social functioning as well as reduction of psychopathological symptoms constitute
      basic criteria for evaluation of effectiveness of psychiatric treatment and
      rehabilitation. Social functioning is often estimated by measuring fulfillment of
      social roles as well as concurrent difficulties and behaviour of patients who can
      be troublesome to others-RASP, and SRPS scales (9, 20). KAS and SAS Scales (11,
      21) focused on measuring social "adjustment" itself are being criticized. The
      LSP, SFS, ILLS (4, 15, 24) can be recognized as scales that are easy to use and
      adopted to the specific functioning of schizophrenics. These scales measure basic
      abilities needed for independent life outside mental hospital. They are being
      used for planning social rehabilitation and community care.

PMID- 8577905
TI  - [The evaluation of subjective quality of life in patients with schizophrenia or
      depression].
AB  - Subjective evaluation of the quality of life was studied in 53 schizophrenics
      (hospitalized, from the day-hospital, and from the rehabilitation unit) and in 12
      depressed patients before and after pharmacological treatment or rehabilitation.
      The self-evaluation questionnaire SF-36 was used. The subjective quality of life
      of depressive patients at baseline was low in comparison to the schizophrenics.
      The best improvement of subjective quality of life after the treatment was found
      in hospitalized schizophrenic patients. Evaluation of the quality of life both
      before and after treatment/rehabilitation did not correlate with doctors'
      estimation of the severity of their illness. Depressive patients expressed more
      negative opinion regarding their physical condition and social activity than did
      the schizophrenics. The positive opinion on patients' health status correlated
      positively with good evaluation of patients' physical condition and good
      performance at home or work.

PMID- 8577906
TI  - [On the need for spiritual help to patients with mental disorders].
AB  - The article presents a psychotherapeutic and spiritual approach to psychotic
      patients. Theoretical assumptions and a practical application (implementation and
      results) are described on the basis of ten years' experience with an open
      religious group at the Psychiatric Department of Warsaw Medical School.

PMID- 8577907
TI  - [The pathogenesis of persecutory delusions in the light of the attribution
      theory].
AB  - Among the present pathogenetic hypotheses of delusions the cognitive model based
      on the attribution theory presents interesting assumptions. The attribution
      theory describes the ways in which we explain causes of events and human
      behaviour from the point of view of common sense psychology, as well as biases
      found in explaining everyday events, known as attribution errors. One of them is
      self-serving bias, which protects self-esteem and distorts attribution processes.
      Kaney, Bentall and co-workers revealed the defensive attributional style in the
      patients with persecutory delusions and after empirical research they suggested
      that delusions are the extreme forms of self-serving bias. After presenting the
      studies of Kaney-Bentall the authors of the article express their doubts
      regarding attributional hypothesis of persecutory delusions.

PMID- 8577908
TI  - [Treatment of delirium tremens with quick administration of diazepam].
AB  - In this efficacy the study of diazepam loading-dose treatment of delirium tremens
      was evaluated in comparison with traditional therapeutic methods. Experimental
      and control groups consisted of 42 and 40 patients respectively. The severity of
      the withdrawal symptoms was evaluated from clinical status, in the experimental
      group CIWA-A score was also employed. Study results suggest high efficacy of the
      loading-dose method, which was characterized by significant shortening of
      psychosis duration (five times shorter in experimental vs. control group). The
      method turned out to be safe, no complications were observed during and after the
      treatment.

PMID- 8577909
TI  - [Urinary beta-hexosaminidase activity as a marker for the monitoring of
      sobriety].
AB  - The aim of this study was to check the usefulness of urine beta-hexosaminidase
      activity determination as a tool of monitoring sobriety in alcohol dependent
      individuals. The examinations were performed in 93 patients undergoing
      detoxification treatment after heavy drinking and in 29 individuals who were
      starting psychotherapeutic treatment after declaring at least 2 weeks abstinence
      period. Enzyme activity was determined using a spectrofluorimetric method and was
      referred to urine creatinine level. In the detoxification group the abnormally
      high beta-hexosaminidase activity was decreasing gradually toward normal values
      within 2 weeks. In less than 10% of the patients atypical increase was observed
      in the course of treatment, what could be attributed to an, influence of
      nonspecific factors or possibly to misbehavior (alcohol drinking or urine samples
      substitution). Among individuals who declared at least 2 weeks abstinence period
      (psychotherapeutic group) in 25% of cases abnormally high enzyme activity was
      detected, what suggested their more recent alcohol drinking.

PMID- 8577910
TI  - [Fetal alcohol syndrome: neurobehavioral effects of prenatal alcohol exposure].
AB  - Alcohol has been established as a teratogenic agent that in prenatal exposure can
      cause a variety of adverse pregnancy outcomes depending on dose, timing, and
      conditions of exposure. Although alcohol, like many other teratogenes, can cause
      alterations in morphology, growth, and neurobehavioral outcomes, this report
      focuses primarily on the latter effects. As with other teratogens causing
      neurobehavioral aberrations, the neurobehavioral effects of prenatal alcohol are
      produced at lower exposure levels than the morphologic or growth effects, and
      except in extreme cases, they are more devastating to the offspring.
      Neurobehavioral effects are difficult to measure, however, because their
      manifestations change with the age of the offspring, and because, at the current
      state of art, their measurement involves outcomes that can be exacerbated or
      ameliorated by postnatal experience. This report describes results of the studies
      on the long-term developmental and behavioral consequences of prenatal alcohol
      exposure.

PMID- 8577911
TI  - [Ontogenesis of sleep-wakefulness regulation].
AB  - In addition to traditional opinions endogenous sleep factors play an important
      role in modern concepts concerning sleep-wake regulation. The recent development
      of neurochemical research including experiments with neuropeptides has modified
      the classical theories of sleeping and waking. Moreover, the influence of
      hormones as cortisol or prolactin on neurotransmitters involved in sleep-wake
      regulation, special problems of the endogenous sleep-rhythms, and the conditions
      of the ontogenetic development are discussed. In addition, a new concept, the so
      called Stimulation theory is described.

PMID- 8577912
TI  - [Psychosocial causal attributions by myasthenia gravis patients. A longitudinal
      study of the significance of subjective illness theories after diagnosis and in
      follow-up].
AB  - The present study evaluates the impact of subjective theories of illness in
      patients suffering from Myasthenia gravis. 46 inpatients were examined after the
      diagnosis had been made (T1) and 6 months later (T2). The following instruments
      have been used: a semistructured interview, the ?Freiburg Personality Inventory?
      (FPI), the ?Freiburg Questionnaire of Coping with Illness (FKV) and a
      questionnaire for the judgement of body experiences (FBK). Ratings concerning
      neurotic symptoms (PSKB), mechanisms of defence (KBAM) and the doctor-patient
      relationship were made by the interviewers and the treating neurologist as well.
      35% of the patients experienced a connection between psychosocial factors
      (stress) and the onset of the disease. As compared with those patients not
      showing a psychosocial causal attribution there are no differences in somatic
      (type and severity of the disease, thymus histology), but in psychological
      variables. Patients attributing their disease to psychosocial factors prove to be
      more depressive, insecure and excitable at T1. They are more likely to be women.
      These findings are in accordance with the results of previous studies. However, 6
      months later (T2) there is some evidence of a psychological stabilization of
      those patients using psychosocial attributions, as different instruments show
      concurrently. Partially they appear now even less depressive. This result is
      understood as a hint for the significance of emotional factors for the process of
      coping with the disease: patients using a psychosocial explanation concept may
      appear more vulnerable at an early stage of the disease. But perhaps, by this
      more emotionally centered coping process, they can reach stability which is
      connected with the construction of a psychosocial theory of the disease.

PMID- 8577913
TI  - [Follow-up and typologic description of requirements in an intensive care unit].
AB  - Presented is the description of the objective, environmental demands of a medical
      intensive care unit (MICU). These are significant as the situational background
      of the subjective perception of working-situation by nurses and physicians.
      Therefore on the one hand a strain-index of the MICU in process of 101 days shows
      the daily variation of straining variables and a cycle of 33 days. On the other
      hand, we found days with a specific pattern of straining variables by a factor
      analysis. These results were discussed on a stress-theoretical view.

PMID- 8577914
TI  - [2 basic problems of psychoanalytic psychotherapy and their philosophical
      revision].
AB  - The presupposition of the cartesian cogito provokes a ?potential decrease of
      transcendental philosophy,? which means, that reevaluation of the scientific
      reflexive reason leads into a metaphysical evacuation. Original philosophical
      subjects develop into subjects of a scientific psychology respectively depth
      psychology. Two fundamental problems, resulting from this historical context of
      philosophy, should be described: Firstly the consciousness, which is objectivated
      and hardened as psyche by the influence of reflection. Secondly the
      unconsciousness, which seems like a hidden psychological entity with an
      indifferent essence. The effort to revise those two problems should be made by
      the use of phenomenological and existential philosophy. The intention of this
      revision is first to reintegrate the isolated reflexive consciousness in a field
      of consciousness and secondly to replace the confrontation with the
      unconsciousness by the dialogue with the fellow being.

PMID- 8577915
TI  - [Freud and Fliess at Achensee].
AB  - Freud has always emphasized the importance of self-analyzing one's own slips.
      When Freud met Fliess at lake Achensee he could not remember that Fliess had
      called his attention to the importance of bi-sexuality in 1897. In answer to it,
      Freud analyzed himself, and realised that he was going to deprive his best friend
      Fliess of his convictions. However, Freud was satisfied with the comment that he
      became more tolerant of other researchers. However, he did not get to the root of
      the problematic nature of his ambition. Thus, a new Freudian slip was to be
      expected. Freud had repressed the visit O. Weininger had paid to him with the
      early manuscript on ?Sex and Character? in 1901. Only precise hints of Fliess
      helped Freud to overcome his amnesia and became aware of the facts repressed. But
      even now Freud did not get to the root of the problematic nature of his ambition.
      He was satisfied with forgetting all private informations of Fliess as soon as
      possible. In 1924 this resulted in a new Freudian slip (Wittels). Freud could
      have spared all these slips by digesting his experience at lake Achensee
      completely (all polemic pamphlets of the year 1906 would not have appeared at
      least).

PMID- 8577916
TI  - Chemical and biological properties of cytotoxic alpha-(N)-heterocyclic
      carboxaldehyde thiosemicarbazones.

PMID- 8577917
TI  - 4-quinolones as potential cardiovascular agents.

PMID- 8577918
TI  - Biochemical mechanisms of resistance to non-cell wall antibacterial agents.

PMID- 8577919
TI  - Inhibitors of HIV proteinase.

PMID- 8577920
TI  - Paclitaxel: a unique tubulin interacting anticancer agent.

PMID- 8577921
TI  - Renin inhibitors.

PMID- 8577922
TI  - Characterization of a functional angiotensin IV receptor on coronary
      microvascular endothelial cells.
AB  - A new class of angiotensin receptors has recently been identified that exhibits
      both high specificity and affinity for the hexapeptide (3-8) fragment of
      angiotensin II, angiotensin IV (AngIV). Here, utilizing radioligand binding, we
      fully characterize AngIV binding at the AT4 receptor on cultured bovine coronary
      venular endothelial cells (CVEC), and report that when AngIV and bFGF are
      presented simultaneously an enhancement of DNA synthesis results that is
      significantly greater than that produced by bFGF alone. The level of DNA
      synthesis was determined by the incorporation of [3H]thymidine into quiescent
      CVEC monolayers following exposure to 10 nM AngIV and 10 ng/ml bFGF for 1, 3, 5,
      7, 9, or 11 days. A significant enhancement of DNA synthesis (P < 0.01) was seen
      following 3, 5, 7, 9 and 11 days exposure. In addition, AngIV does not bind to
      bFGF or heparin, and conversely, bFGF is unable to compete for AngIV binding
      which suggests that this synergistic response is mediated by independent
      receptors for these ligands. Results of this study indicate that microvascular
      endothelial cells are significantly more responsive to bFGF in the presence of
      nanomolar concentrations of AngIV.

PMID- 8577923
TI  - Inhibition of substance P-induced vascular leakage in rat by N-acetyl-neurotensin
      (8-13).
AB  - Substance P (SP) administered 40 micrograms/kg s.c. to pentobarbital-anesthetized
      rats induced salivation and leakage of plasma constituents into the skin, muscle,
      trachea, esophagus and bladder, as measured by Monastral blue B labeling of small
      blood vessels or by extravasation of Evans blue dye into tissues. These SP
      effects were inhibited by N-acetyl-neurotensin-(8-13) (Ac-NT-(8-13)) and by CP
      96,345, a nonpeptide SP receptor antagonist. Intralumenal injection of Ac-NT-(8
      13) or CP-96,345 into the bladder reduced SP-induced leakage of Evans blue dye
      but not dye leakage into the pawskin, indicating a localised drug action. Ac-NT
      (8-13) appears to act directly on discrete sites in skin and in mucous membranes
      to functionally antagonize the inflammatory effects of SP.

PMID- 8577924
TI  - Vasoconstrictor effects of galanin and distribution of galanin containing fibres
      in three species of elasmobranch fish.
AB  - Galanin is found in perivascular sympathetic neurons in a wide range of
      vertebrate species. In placental mammals, galanin has either no effect on blood
      pressure, or weak depressor effects, but in other vertebrates it has been shown
      to be a potent pressor agent. To investigate how extensive the vasoconstrictor
      effects of galanin may be in the vertebrates, the vascular effects of galanin
      were tested in two species of shark, Heterodontus portusjacksoni, and
      Hemiscyllium ocellatum, and a ray, Rhinobatos typus. Nerve fibres showing
      immunoreactivity to galanin were located surrounding gut blood vessels, but were
      absent from branchial efferent arteries in all three species. Intravenous
      injection of galanin caused a significant rise in caudal arterial blood pressure
      in H. portusjacksoni and H. ocellatum, but no change in R. typus. Contraction of
      segments of pancreatico-mesenteric artery were measured in an organ bath also.
      Galanin (10(-6) M) caused 21-38% of the maximum K+ induced contraction in all
      species, but no response in efferent branchial arteries from R. typus. In
      conclusion, in three elasmobranchs, a galanin-like peptide is present in
      perivascular nerve fibres, and galanin causes differential vasoconstriction in
      vascular beds. These data extend the number of vertebrate groups in which galanin
      has been shown to be a vasoconstrictor peptide.

PMID- 8577925
TI  - Effects of galanin on proinsulin mRNA and insulin biosynthesis in normal islets.
AB  - Whether the potent insulinostatic neuropeptide galanin also inhibits insulin
      production in normal islets is not known. Therefore, isolated mouse islets were
      incubated for 90 min in 2.8 or 16.7 mmol/l glucose and 3H-labelled leucine with
      addition of mouse galanin at 1, 10 or 100 nmol/l. Galanin potently inhibited
      glucose-stimulated insulin secretion at both 10 and 100 nmol/l (P < 0.05), and
      proinsulin biosynthesis was slightly inhibited at 100 nmol/l (P < 0.05). Also,
      mouse islets were incubated for 48 h at 5 or 16.7 mmol/l glucose with galanin at
      1, 10 or 100 nmol/l and proinsulin mRNA was determined by hybridisation of
      extracted RNA with digoxigenin-labelled oligonucleotide insulin probe. Proinsulin
      mRNA levels were approximately doubled by glucose at 16.7 mmol/l compared at 5
      mmol/l (P < 0.05). Galanin did not affect islet proinsulin mRNA levels.
      Therefore, galanin seems to mainly regulate insulin secretion without any
      important role in the regulation of insulin availability in normal islets.

PMID- 8577926
TI  - Neurotensin-like immunoreactivity in odontoblasts and their processes in rat
      maxillary molar teeth and the effect of pulpotomy.
AB  - A strong neurotensin-like immunoreactivity (NT-like IR) was detected in the
      odontoblast cells of the rat teeth. 4 h after a partial pulpotomy performed in
      two maxillary molar teeth a decreased NT-like IR was observed in the odontoblast
      layer located at the vicinity of the lesion together with edema and nuclear
      pyknosis. NT-like IR became further decreased after 24 h. After 7 days NT-like IR
      had almost fully disappeared with signs of necrosis of the dental pulp and
      infiltration of polymorphonuclear lymphocytes. It seems possible that NT like
      peptides in the odontoblast cell layer may play a role, e.g., in dentinogenesis
      and/or nociception.

PMID- 8577927
TI  - Characterisation of the processing by human neutral endopeptidase 24.11 of GLP
      1(7-36) amide and comparison of the substrate specificity of the enzyme for other
      glucagon-like peptides.
AB  - The post-secretory processing of the potent insulinotropic peptide hormone, GLP
      1(7-36)amide, probably involves one or more of a small group of membrane-bound
      ectopeptidases. Reported here, is the characterisation of the endoproteolysis of
      human GLP-1(7-36)amide by the recombinant human form of neutral endopeptidase
      (NEP) 24.11, which is one of the best characterised and widely-distributed of
      ectopeptidases and is involved in the processing of other peptide hormones. The
      products of the limited endoproteolysis were characterised by mass and primary
      structure following fractionation using high performance liquid chromatography.
      The rate of this endoproteolysis by NEP 24.11 was estimated and compared to that
      of GLP-1(7-36)amide-related peptides. GLP-1(7-36)amide appears to be good
      substrate for NEP 24.11 with most, but not all potential target bonds being
      cleaved. Also, the structurally-related peptides, secretin and glucagon appear to
      be good substrates whereas GIP and exendin-4 are very poor substrates. That the
      GLP-1(7-36)amide super-agonist, exendin-4 is a poor substrate for NEP 24.11 is
      significant for the possible use of this peptide as a prototype for the
      development of clinically-useful peptide agonists. Further studies should reveal
      whether NEP 24.11 is important for the metabolic clearance of GLP-1(7-36)amide
      and will be highly relevant for the attempts to realise the suggested therapeutic
      value of GLP-1(7-36)amide.

PMID- 8577928
TI  - Effect of antrectomy and truncal vagotomy on erythromycin induced pancreatic
      polypeptide secretion.
AB  - Erythromycin, a motilin agonist, enhances gastrointestinal motility but also
      stimulates endogenous pancreatic polypeptide (PP) secretion. We investigated
      whether the effect of erythromycin on PP release is dependent on (1) prokinetic
      activity of erythromycin generated from the antrum and (2) the long vagus nerve
      since erythromycin acts via cholinergic neurons. Erythromycin induced PP
      secretion was determined in 14 patients with antrectomy (6 patients with Billroth
      I type anastomosis, 8 patients with Billroth II type anastomosis), in 6 patients
      with truncal vagotomy and pyloroplasty but without gastric resection and in 8
      healthy controls. Plasma PP levels in response to erythromycin (3 mg/kg i.v.)
      were determined at regular intervals for 180 min. Erythromycin induced a
      significant increase in plasma PP in the control subjects from 22 +/- 4 pmol/l
      (basal) to 49 +/- 4 pmol/l at 10 min. In the patients with truncal vagotomy
      plasma PP secretion after erythromycin was significantly (P < 0.05) increased
      (peak increment vs. basal: 98 +/- 10 pmol/l vs. 27 +/- 2 pmol/l) and prolonged
      compared to controls. In the patients with antrectomy no significant increases in
      plasma PP over basal were observed after erythromycin infusion. It is concluded
      that erythromycin stimulates PP secretion in healthy controls. The PP response to
      erythromycin is exaggerated after truncal vagotomy but absent after antrectomy
      indicating that the antrum is essential for erythromycin induced PP secretion.

PMID- 8577929
TI  - Beta-adrenoceptor stimulation increases neuropeptide Y release from sympathetic
      nerves in intact rats.
AB  - This study was undertaken to assess in conscious normotensive rats the effects of
      beta-adrenoceptor stimulation on plasma neuropeptide Y (NPY) levels. Wistar rats
      were subjected to adrenal demedullation on the right side and were either
      adrenalectomized or sham-operated on the left side. Eleven days later, the
      conscious rats were infused i.v. for 30 min with either isoproterenol (10 ng/min)
      or its vehicle. Plasma NPY levels were significantly lower (23.8 +/- 2.6 pM,
      means +/- S.E.M., n = 12, P < 0.01) in vehicle-treated medullectomized rats than
      in corresponding sham-operated controls (36.7 +/- 4.1 pM, n = 12). The
      medullectomized rats infused with isoproterenol showed plasma NPY levels (36.7 +/
      3.3 pM, n = 11) comparable to those of sham-operated rats having received the
      vehicle. These data therefore demonstrate that plasma NPY levels are lower in
      rats without adrenal medulla and that in these animals isoproterenol increases
      NPY release, most likely by activating pre-synaptic beta-adrenoceptors.

PMID- 8577930
TI  - Chromogranin A: current status as a precursor for bioactive peptides and a
      granulogenic/sorting factor in the regulated secretory pathway.

PMID- 8577932
TI  - Structure-activity studies of RFamide analogues on central neurones of Helix
      aspersa.
AB  - The effects of FMRFamide were compared with those of FMRFamide analogues,
      FLRFamide, LFRFamide, FFRFamide, LLRFamide, D-FMRFamide, F-D-MRFamide and FM-D
      RFamide, and the fragments, MRFamide and LRFamide, on identified central
      neurones, F1, F2, F5 and E16, of the snail Helix aspersa, using intracellular
      recording and two electrode voltage clamp techniques. All FMRFamide analogues
      showed an inhibitory effect on F1 neurones with an order of potency: FLRFamide >
      FMRFamide > FFRFamide > LFRFamide >> LLRFamide. FMRFamide and FLRFamide exhibited
      a biphasic response on F2 neurones. At lower concentrations (< 10 microM), both
      peptides usually only excited while at higher concentrations (> 30 microM),
      exhibited an excitation followed by an inhibition. FFRFamide only excited F2
      while LFRFamide and LLRFamide only inhibited F2. LRFamide and MRFamide (100
      microM) were inactive on both F1 and F2. FLRFamide, LFRFamide, LLRFamide,
      FFRFamide and D-FMRFamide showed cross-interaction on the outward current induced
      by FMRFamide in F5. All peptides induced an outward current and also reduced the
      FMRFamide-induced current reversibly. In contrast, MRFamide, LRFamide and F-D
      MRFamide failed to have direct effects on these neurones nor interact with the
      FMRFamide-induced current. We conclude that on F2 neurones Phe is essential for
      the activation of the RFamide receptor mediating the excitation and Met or Leu
      are important to activate the RFamide receptors mediating the inhibition. Removal
      of the N-terminal Phe, to give LRFamide and MRFamide render the peptides
      inactive. Therefore a tetrapeptide sequence is essential for the biological
      activity of FMRFamide analogues on these Helix neurones. FLRFamide, LFRFamide,
      LLRFamide, FFRFamide and D-FMRFamide exhibit a cross-interaction with FMRFamide.
      It is possible that these peptides also act on the same class of RFamide
      receptors as agonists to cause cross desensitization.

PMID- 8577931
TI  - PreproPACAP-derived peptides occur in VIP-producing tumours and co-exist with
      VIP.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a newly discovered
      neuropeptide which exists in two biologically active forms: PACAP-38 consisting
      of 38 amino acids and PACAP-27, a peptide corresponding to the N-terminal 27
      amino acids of PACAP-38. Both PACAPs are derived from a 176 amino acid precursor
      (preproPACAP) which in addition gives rise to a 29 amino acid peptide, designated
      PACAP-related peptide (PRP). The presence of the three preproPACAP-derived
      peptides (PACAP-38, PACAP-27 and PRP) in tumour tissue from nine patients with
      VIP-producing tumours (pancreatic carcinoma, neuroblastoma, ganglioneuroma and
      pheochromocytoma) and eleven patients with non-VIP-secreting tumours (gastrinoma,
      glucagonoma, somatostatinoma, neuroblastoma) was examined by specific
      radioimmunoassays. In seven out of the nine VIP-secreting tumours elevated
      concentrations of all the three preproPACAP-derived peptides were found compared
      with normal tissue, while the concentrations in the non-VIP-secreting tumours
      were within the normal range. PACAP-38 was in all cases the dominating peptide,
      the concentration ranging from 41 to 3606 pmol/g. When tumour extracts were
      fractionated on Sephadex G50 column, tricine gel electrophoresis or reverse-phase
      HPLC immunoreactive components corresponding to synthetic PACAP-38, PACAP-27 and
      human PRP were identified, suggesting that preproPACAP was fully processed.
      Immunocytochemical examination showed PACAP-immunoreactive cells in the tumour
      tissue which also stained for VIP. This co-localization of PACAP and VIP was
      confirmed by double-staining experiments on the same sections, demonstrating
      PHM/VIP mRNA and PACAP-immunostaining in the same cells.

PMID- 8577933
TI  - Brain angiotensin receptor subtypes AT1, AT2, and AT4 and their functions.

PMID- 8577934
TI  - Effects of cholecystokinin and glucagon-like peptide 1 on the secretion of
      pancreatic polypeptide in mice.
AB  - The gut hormones, cholecystokinin (CCK) and truncated glucagon-like peptide 1
      (GLP-1(7-36)amide or GLP-1) both stimulate insulin secretion and affect glucagon
      secretion in mice, but their effects on the secretion of other islet hormones
      have not been established in rodents. In the present study, we have examined the
      influence of the C-terminal octapeptide of CCK, CCK-8, and GLP-1 on the secretion
      of pancreatic polypeptide (PP) in the mouse by the use of a radioimmunoassay for
      rodent PP. Mice were injected intravenously with CCK-8 (doses in the range of
      0.053-5.3 nmol/kg) or with GLP-1 (doses in the range of 1-32 nmol/kg) and blood
      was sampled at 2, 6 or 10 min after the injection. Controls were injected with
      saline. It was found that CCK-8 at 5.3 nmol/kg increases plasma levels of both PP
      and insulin when the sample was taken at 2 min, but not at 6 or 10 min, after
      injection. These effects were blocked by the selective CCKA-receptor antagonist,
      L-364,718 (2.4 micromol/kg). GPL-1 increased plasma insulin levels at 32 nmol/kg
      at 2 and 6 min after the injection, but plasma PP levels were unaltered. In
      conclusion, this study, using a newly developed radioimmunoassay for PP in
      rodents, shows that CCK-8 but not GPL-1 stimulated PP secretion in mice at dose
      levels where both peptides stimulate insulin secretion. Furthermore, PP secretion
      in response to CCK-8 showed a similarity with that of insulin in terms of dose-
      and time-response characteristics as well as sensitivity to CCKA-receptor
      antagonism.

PMID- 8577935
TI  - Binding of valsartan to mammalian angiotensin AT1 receptors.
AB  - The binding characteristics of the angiotensin AT1 receptor antagonist valsartan
      were investigated in different animal species and tissues. Using
      [125I](Sar1,Ile8) angiotensin II as radioligand, affinity constants were
      determined in liver and adrenal rat and marmoset, human adrenal and in rat aortic
      smooth muscle cells. In all tissues tested, valsartan had a greater affinity for
      the AT1 receptor than losartan (on average 5-fold). The affinities of both
      antagonists were up to 30 times weaker in the dog tissues [3H]Valsartan bound
      with high affinity (Kd 1.44 nmol/l) to the rat aortic smooth muscle cell AT1
      receptor. Binding was saturable and reversible. Non-specific binding was low
      (10%). Reports that [3H]losartan binds to a non-angiotensin II binding site in
      rat liver and in other tissues could be confirmed. [3H]Valsartan on the other
      hand bound only to the AT1 receptor. Using a competition binding assay with
      [3H]losartan on rat liver membranes it could be shown that valsartan can bind to
      the 'losartan binding site', but at a 10,000-fold less affinity than for the AT1
      receptor. Valsartan is therefore a highly specific and selective antagonist of
      the AT1 receptor. Due to its high affinity and low non-specific binding it is a
      suitable radioactive antagonist for the study of the distribution and function of
      the angiotensin AT1 receptor.

PMID- 8577936
TI  - Pericardial repair depresses canine cardiac catecholamines and met-enkephalin.
AB  - Decreased cardiac catecholamines were observed following incision and repair of
      the pericardium in sham-operated vs. unoperated control dogs. Animals were
      assigned to five groups: unoperated, sham-operated intact pericardia, open
      pericardia, sutured pericardia and complete ventricular sympathectomy. Hearts
      were collected four weeks after surgery. Sympathectomy decreased catecholamine
      content when compared to all other groups. Hearts with open/sutured pericardia
      contained significantly less catecholamines than controls. When the pericardium
      was intact or left open following incision, cardiac catecholamines were unchanged
      compared to unoperated controls. Since opioid peptides are colocalized with
      catecholamines, we measured met-enkephalin and met-enkephalin-arg-phe,
      proenkephalin A peptide products, in parallel samples. Similar to norepinephrine,
      met-enkephalin was decreased following both sympathectomy and pericardial repair.
      However, met-enkephalin-arg-phe, which may be more associated with the myocardium
      than its innervation, was not changed by any treatment. The sutured pericardium
      more than the stress of surgery apparently alters the tissue catecholamines and
      enkephalin. This may have resulted from the mechanical friction at the site of
      repair. Epinephrine and met-enkephalin contents in sympathectomized hearts were
      significantly lower than unoperated controls but were not significantly different
      from the intermediate values observed in the sutured group. The functional
      consequences of these changes on neuroendocrine status are unclear and will
      require further evaluation. The results also emphasize the need for careful
      attention to proper controls for surgical studies.

PMID- 8577937
TI  - VIP antagonist demonstrates differences in VIP- and PHI-mediated stimulation and
      inhibition of ACTH and corticosterone secretion in rats.
AB  - Previous studies in our laboratory have demonstrated that PVN administration of
      equimolar doses of VIP and PHI induce similar increases in plasma ACTH and CORT
      concentrations via the release of CRF and vasopressin in fasted, freely moving
      rats studied during the early light cycle. The purpose of these investigations
      was to determine whether VIP and PHI act via the same receptor and/or mechanism.
      Individual studies involving the PVN administration of either VIP or PHI in doses
      ranging from 0.3 to 30.0 nmol/rat demonstrated that VIP increases both ACTH and
      CORT secretion throughout the administered range. In contrast, PHI was an
      effective stimulant in doses up to 15 nmol/rat but had no effect on either ACTH
      or CORT at a dose of 30 nmol/rat thus yielding a bell-shaped dose-response curve.
      When increasing doses of PHI (0.15-3.0 nmol/rat) were administered against a
      background of VIP (3.0 nmol/rat) predictably additive responses were observed;
      however, when increasing doses of VIP (0.15-3.0 nmol/rat) were administered with
      PHI (3.0 nmol/rat) only the higher doses of VIP facilitated the PHI-induced
      secretion while the lower doses of VIP actually reduced the PHI-induced ACTH
      secretion. Finally, pretreatment with [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP, anVIP
      (1.5 nmol/rat) totally suppressed VIP-induced ACTH secretion but had no effect on
      PHI-induced secretion. These studies collectively suggest that VIP and PHI
      utilize different receptors/mechanisms to regulate HPA secretion. Furthermore,
      when a range of doses of anVIP (1.5-30.0 nmol/rat) was tested against VIP (3.0
      nmol/rat), ACTH secretion was totally suppressed at all doses of the antagonist.
      However, the maximal reduction of CORT secretion occurred at the lowest dose of
      anVIP and increasing doses were less and less effective, suggesting that not only
      PHI but VIP may also stimulate and inhibit HPA secretion. While both the
      stimulatory and the inhibitory actions of PHI appear to involve ACTH, only the
      stimulatory action of VIP is ACTH-dependent.

PMID- 8577938
TI  - Opposite changes in the content of oxytocin- and vasopressin-like immunoreactive
      peptides in the rat thymus during aging.
AB  - The content of oxytocin- and vasopressin-like immunoreactive (IR) peptides was
      measured in the thymic extract of 2, 5, 10, 15 and 20 month-old rats by
      radioimmunoassay before or after fractionation by high-pressure liquid
      chromatography. In both cases the content of the oxytocin-like IR peptide, which
      behaved like authentic oxytocin in the chromatography column, increased during
      aging. Compared to 2 month-old rats a significant 30% increase was observed in 5
      month-old rats, whereas the maximal increase (200%) was found in 20 month-old
      rats. In contrast, the content of the vasopressin-like IR peptide, which behaved
      like authentic arg8-vasopressin in the chromatography column, decreased during
      aging. The decrease (30%) was evident in 5 month-old rats, and was maximal (80%)
      in 15 month-old rats. The present results suggest that the mechanisms regulating
      the content of oxytocin- and vasopressin-like IR peptides in the rat thymus
      undergo differential changes during aging. These processes might be linked to
      thymic involution.

PMID- 8577939
TI  - Binding and agonist/antagonist actions of M35, galanin(1-13)-bradykinin(2-9)amide
      chimeric peptide, in Rin m 5F insulinoma cells.
AB  - The chimeric peptide M35 [galanin(1-13)-bradykinin(2-9) amide] is a high-affinity
      galanin receptor ligand acting as a galanin receptor antagonist in the rat spinal
      cord, rat hippocampus and isolated mouse pancreatic islets. We have radiolabelled
      M35 and performed equilibrium binding studies with [125I]M35 on the rat
      pancreatic beta-cell line Rin m 5F, whereby we show the existence of high
      affinity binding site (KD = 0.9 +/- 0.1 nM) with a Bmax of 72 +/- 3 fmol/mg
      protein. Galanin displaces [125I]M35 with the same affinity (KD = 1 nM) as it
      displaces [125I]galanin. Displacement of [125I]galanin by M35 from Rin m 5F cell
      membranes shows the presence of two binding sites for M35 with KD-values of 0.3
      +/- 0.1 nM and 0.52 +/- 0.03 microM, respectively. The GTP- and pertussis toxin
      sensitivity of M35 binding to Rin m 5F membranes shows that binding of [125I]M35
      is almost completely abolished by the presence of GTP or after pertussis toxin
      treatment of the cells, indicating an agonist-like binding of M35 to the galanin
      receptors. M35 has a dual effect on the galanin mediated inhibition of forskolin
      stimulated cyclic AMP production in Rin m 5F cells: at low concentrations M35
      antagonises the effect of galanin, whereas at concentrations above 10 nM M35 acts
      as a galanin receptor agonist. These agonist-like effects of galanin and M35 are
      not additive, thus the mixed agonist/antagonist properties arise from the
      chimeric nature of M35[galanin(1-13)-bradykinin(2-9)amide] acting solely at
      galanin receptors.

PMID- 8577940
TI  - Effects of neuropeptide FF analogs on morphine analgesia in the nucleus raphe
      dorsalis.
AB  - The effect of microinfusion into the nucleus raphe dorsalis (DR) of neuropeptide
      FF (NPFF) analogs on the antinociceptive effects of morphine was evaluated in
      rats, using the tail-immersion test. infusion of morphine into the DR induced a
      dose-dependent analgesia significantly reversed by co-infusion of 2.5 nmol opioid
      antagonist, naloxone. Similarly, 2.5 nmol NPFF and (1DMe)Y8Fa(D-Tyr-Leu-(NMe)Phe
      Gln-Pro-Gln-Arg-Phe-NH2) or (3D)Y8Fa(D-Tyr-D-Leu-D-Phe-Gln-Pro-Gln-Arg-Phe-NH2),
      two neuropeptide FF analogs, inhibited morphine analgesia, although these
      peptides had no effect on nociceptive thresholds. This anti-opioid effect is
      indirect since NPFF analogs displayed no significant affinity towards mu and
      delta opioid binding sites in the DR. After intracerebroventricular infusion,
      morphine produced the same degree of analgesia as that measured after infusion
      into the nucleus raphe dorsalis and both NPFF analogs reversed morphine
      antinociception. This result is the first direct evidence that neuropeptide FF
      may act on opioid system at the DR and that several nuclei are involved in the
      suppression of morphine-induced antinociception.

PMID- 8577941
TI  - Bronchodilating effects of natriuretic and vasorelaxant peptides compared to
      salbutamol in asthmatics.
AB  - In animal studies, the bronchial effects of urodilatin (URO, CDD/ANP-95-126, INN:
      ularitide) were superior to those of cardiodilatin/atrial natriuretic peptide
      (CDD, CDD/ANP-99-126). We compared the bronchodilating properties of intravenous
      URO and CDD in 36 clinically stable asthmatics showing a beta 2-agonist-induced
      increase of the FEV1 by > or = 15%. Any aerosol medication was discontinued for
      at least 8 h prior to the study. After baseline measurements of lung function
      parameters (FEV1, VC, PEF, MEF75, MEF50, MEF25) an intravenous infusion of 5.7,
      11.4 or 17.1 pmol/kg/min URO or CDD was administered for 40 min in the morning.
      All measurements were repeated every 10 min during the infusion, for 30 min
      thereafter, and after the inhalation of 1.25 mg salbutamol (SALB). Both peptides
      had significant effects. While 11.4 pmol/kg/min URO dilated the central airways
      (FEV1, PEF, MEF75) slightly more potently than the peripheral bronchioles (MEF50,
      MEF25), 17.1 pmol/kg/min URO was as effective as SALB at all levels of the
      tracheobronchial tree. CDD reached only 50% of the SALB effect without a
      predominant localization of its action. The cardiovascular parameters revealed a
      significantly stronger vasorelaxant activity of CDD. In conclusion, the dose
      dependent bronchodilating properties of intravenous URO were significantly
      superior to those of CDD.

PMID- 8577942
TI  - Initiating and responsible enzyme of arginine vasopressin degradation in human
      placenta and pregnancy serum.
AB  - The hydrolysis of arginine vasopressin (AVP) by human placental subcellular
      fractions and pregnancy sera was studied in the presence of selective inhibitors
      and the antibody against pregnancy serum oxytocinase (P-LAP) (EC 3.4.11.3) by
      measuring liberated amino acids by high-performance liquid chromatography (HPLC).
      AVP degradation by placental subcellular fractions and pregnancy sera was
      inhibited by bestatin. The IC50 values of bestatin on AVP degradation by
      placental subcellular fractions and pregnancy sera were similar to that of this
      inhibitor on the P-LAP measured by L-Leu-p-nitroamnilide as a substrate (LAP
      activity), which we reported previously. Our immunotitration study clearly showed
      that the initiating and responsible protease in AVP degradation in human placenta
      and pregnancy serum is P-LAP. Since N-benzylcarbonyl-valyl-prolinal (Z-Val
      prolinal), a selective inhibitor of post-proline endopeptidase, and
      phosphoramidon, a putative endopeptidase-24.11 inhibitor, could not significantly
      influence the degradation of AVP by placental microsomal fractions. Neither
      enzyme seems to be actively involved in AVP degradation.

PMID- 8577943
TI  - Expression of angiotensin I-converting enzyme in the human gastric HGT-1 cell
      line.
AB  - We have previously shown that angiotensin I-converting enzyme (ACE) was expressed
      by epithelial cells of the rabbit gastric mucosa. In a search to obtain a cell
      model to study the regulation of ACE expression of gastric origin and its
      relationship with gastrin-cholecystokinin peptides, which have been proposed as
      ACE substrates, we investigated whether the HGT-1 human gastric cell line, which
      expresses gastrin, could also express ACE, using enzymatic and immunodetection
      methods as well as Northern-blot analysis and polymerase chain reaction. Results
      show that HGT-1 cells expressed a protein with a molecular weight of 130-140 kDa
      whose enzymatic and immunological properties were identical to those of ACE. More
      than 80% of ACE activity was found to be ectoenzymatic. However,
      immunocytochemical localization has mainly shown an intracellular localization,
      suggesting that most of intracytoplasmic ACE was not enzymatically active. In
      addition, Northern-blot analysis and polymerase chain reaction showed that the
      mRNA encoding that protein displayed a size and a sequence identical to those of
      somatic ACE. It therefore appears that the HGT-1 cell line could be a useful
      model to study both the regulation of gastric ACE and its interactions with
      gastrin-cholecystokinin peptides.

PMID- 8577944
TI  - Neurochemical markers of human fungiform papillae and taste buds.
AB  - The presence of distribution of several neurochemical markers in human fungiform
      papillae and taste buds were investigated by the immunohistochemical technique.
      The gustatory cells of the taste buds are in synaptic contact with sensory nerve
      endings, and considering the taste buds strictly as specialized sensory organs,
      the amounts and distribution of some of the neurochemical markers were different
      to what we expected. For example, few structures showed immunoreactivity to the
      tachykinins substance P (SP), calcitonin gene-related peptide (CGRP), and
      neurokinin A (NKA) also for the peptides vasoactive intestinal polypeptide (VIP),
      neuropeptide tyrosine (NPY) and galanin, low amounts of immunoreactivity
      occurred. On the other hand, using antibodies to protein gene product 9.5 (PGP
      9.5), protein S-100, and glutamate, numerous nerve fibres and/or immunoreactive
      cells were found in the fungiform papillae, in the epithelium, in the connective
      tissue and around blood vessels, as well as in or near taste buds. Incubation
      with the antibodies against somatostatin, enkephalin, bombesin, peptide histidine
      isoleucine amide (PHI), cholecystokinin (CCK)/gastrin and dopamine-beta
      hydroxylase (DBH) was negative for the fungiform papillae. In conclusion, the
      present study has shown several immunoreactive structures using antibodies
      against certain neurochemical markers. Further investigations will hopefully
      correlate these morphological findings with functional taste perception data.
      Future studies of patients with taste disorders or other pathological changes
      correlated with taste and tongue will also be of utmost importance.

PMID- 8577945
TI  - The detection level.
AB  - A statistical measure, the detection level, that conveys information about the
      risk of type II errors in a way that is easily understandable to the
      statistically unsophisticated decision maker is proposed. The detection level
      answers the question: "How big should an effect have been in order to be detected
      in this way?" Given a statistical test with the critical level (size) alpha*, the
      detection level of this test is the smallest effect that would, with at least
      probability 1-alpha*, lead to a significant outcome (P < alpha*) of the test. It
      is proposed that detection levels should be calculated as a standard procedure in
      toxicity reviews, and in particular in reports from toxicologists to decision
      makers.

PMID- 8577946
TI  - Holistic risk assessment: an emerging process for environmental decisions.
AB  - A holistic risk assessment (HRA) strategy is proposed as an alternative,
      inclusive paradigm which builds upon the traditional risk assessment process
      described by the National Academy of Sciences. This proposed process expands
      beyond the traditional process in that it: (i) includes parallel and integrated
      assessments for ecological risk and human health risks; (ii) recognizes the
      presence of competing risks that may arise from implementation of risk management
      decisions; (iii) is an iterative and nonsequential process that highlights the
      importance of risk characterization and the need for comparisons; (iv) has focus
      on presenting a series of risk choices that take into consideration parameters
      specific to exposed populations and ecosystems; and (v) involves communication as
      the first step between risk assessors and risk managers, with subsequent
      communication of the results of the assessment to clients and the public. This
      HRA strategy is illustrated by a case study on methyl mercury. Specific research
      is proposed for future improvements in this area.

PMID- 8577947
TI  - Realistic risk assessment.
AB  - A controversy over cancer risk has undermined trust in the scientific basis of
      regulation. Drinking water and pesticide programs are in chaos because "potential
      cancer risk" cannot produce practical standards. The risk controversy involves a
      dispute over the most fundamental scientific standards, namely what is and what
      is not a positive result. Here it is shown that the lowest effective dose (LOEL)
      of well-studied carcinogens is a firm and reproducible quantity that can serve as
      undisputed basis for safety standards. "Realistic risk assessment" is proposed,
      based on the immediately available LOEL, as a transitional measure to eliminate
      the controversy over assumed risks. A traditional regulatory safety margin, over
      which regulators have explicit authority, would produce traditional safety
      standards when based on the lowest effective dose. Superfund clean-up targets
      based on one in one-million potential cancer risk are equivalent to an
      approximately 10,000-fold safety margin over real risk. Realistic risk opens the
      way for a reevaluation of regulatory priorities based on the fact that a 5-fold
      safety margin for the real carcinogen arsenic is now in use and has proven safe.

PMID- 8577948
TI  - Progressive application of autoradiography in pharmacokinetic and metabolic
      studies for the development of new drugs.
AB  - Autoradiographic data of distinctive tissue distributions of 14C atoms obtained
      by labeling at two different positions of a new drug suggest the metabolic fates
      of each labeled compound in experimental animals. A more accurate determination
      of blood-brain barrier (BBB) damage in several regions was indicated by
      semimicroautoradioluminography, based on no passage of dopamine through the BBB.
      Autoradioluminography (ARLG) was useful for quantitative validation of whole body
      autoradiography (WBA) with both ordinal X-ray film and other detectors. In frozen
      specimens, a good correlation was obtained between the relative radioactivity,
      photostimulated luminescence (PSL), and liquid scintillation counting (LSC)
      values in each organ or tissue. However, the correlation was disturbed in lung,
      brain, bone, and adipose tissue after freeze-drying. In order to be listed in the
      regulatory items, WBA data must be quantitative as well. The paste-mold method
      presented here can be used to support WBA data. The thin-layer chromatography
      (TLC)-ARLG technique and its applications are also presented in this article. A
      blood concentration-time curve of both the parent compound and its unknown
      metabolites can be estimated with this technique.

PMID- 8577949
TI  - Influence of soil half-life on risk assessment of carcinogens.
AB  - Risk estimates for contaminants in soil are currently calculated assuming that
      concentrations remain unchanged over time. In reality, biological and
      physicochemical processes can substantially diminish contaminant concentrations
      in soil. For exposure periods typically evaluated in USEPA risk assessments,
      failure to consider the decline in contaminant levels from environmental
      transport and degradation can result in a significant overestimation of the
      average daily dose of toxicant. This overestimation may be up to 2- to 3-fold for
      compounds with long half-lives (15-20 years) in soil and as much as 40-fold for
      compounds with short half-lives (0.5 years). Overestimation of dosages affects
      estimation of cancer risks because of the assumption that the probability of
      cancer increases directly with the cumulative dose of carcinogen. Thus, assuming
      static contaminant concentrations in soil adds unacknowledged conservatism to
      cancer risk estimates and target concentration limits. Furthermore, as
      significant time may elapse before future-use scenarios could possibly occur,
      soil half-life can affect the estimation of noncarcinogenic health hazards as
      well. Therefore, an increase in target concentration limits for some compounds
      could be allowed and corresponding remediation costs reduced by considering how
      soil half-life changes the dosage calculation. Specific examples of the influence
      of soil degradation rates on estimates of cancer risk are presented and the
      degree of added conservatism imparted to risk assessments through assumption of
      static site contaminant levels is discussed. Considering the potential importance
      of this parameter for risk assessment and risk management decisions, soil
      degradation of contaminants under site-specific conditions should be performed
      whenever possible and incorporated into the risk assessment exercise. When the
      soil degradation rate cannot be measured or reliably predicted, an estimate of
      the degree of conservatism should be made to provide risk managers with an
      appreciation of the degree of uncertainty in the calculation of risk.

PMID- 8577950
TI  - Risk identification using structural concepts: the potential carcinogenicity of
      praziquantel.
AB  - The potential of praziquantel (PZ) to induce cancers in rodents was evaluated
      using a structure-activity relational expert system (CASE/MULTICASE). The
      analyses indicated that based upon structural features PZ had the potential for
      being a "nongenotoxic" carcinogen. The potential risk to humans of nongenotoxic
      carcinogens is considered to be much less than that posed by "genotoxic" ones.
      Moreover, PZ has demonstrated therapeutic effectiveness against parasitic
      diseases that affect millions of individuals. Additionally, PZ was developed to
      replace antiparasitic agents which were genotoxic rodent carcinogens. Thus, on
      balance, the beneficial effects of PZ appear to outweigh its potential for
      causing harm to humans.

PMID- 8577951
TI  - The development of occupational exposure limits for chemical substances in China.
AB  - This paper presents a comprehensive review of the occupational exposure limits
      (OELs) of chemical substances in China. It provides historical background on the
      development of OELs in this country, with a complete list of traditionally
      adopted and newly developed OELs for chemicals in workplaces. The philosophical
      thoughts, the administrative system, the scientific protocols for setting and
      amending health standards, with emphasis on making health a basic criterion for
      setting health standards, strengthening epidemiological studies of the human
      population, integrating epidemiological and toxicological studies, considering
      technological and economical feasibilities, and making full use of literature
      information sources are discussed. Further perspectives with respect to practical
      issues of maximum allowable concentration and time-weighted average, selection of
      safety factors, and establishment of biological exposure limits are also
      considered, with the authors' contributions to a discussion on these topics.

PMID- 8577952
TI  - Stimulating effects of ionizing radiation: new issue for regulatory policy.

PMID- 8577953
TI  - Utilizing uncertainty factors in minimal risk levels derivation.
AB  - The Agency for Toxic Substances and Disease Registry (ATSDR) utilizes chemical
      specific minimal risk levels (MRLs) to assist in evaluating public health risks
      associated with exposure to hazardous substances. During MRL derivation,
      uncertainty factors (UF) are used. Under current ATSDR methodology, default UFs
      of 10 are applied to extrapolate from a lowest-observed-adverse-effect level
      (LOAEL) to a no-observed-adverse-effect level (NOAEL), for interspecies
      extrapolation and for intraspecies variability. However, chemical-specific
      toxicity information has sometimes made it necessary and appropriate to deviate
      from using the standard UF of 10. Since its inception in January 1993 until
      December 1994, ATSDR's Inter-agency MRL Workgroup has derived 46 inhalation and
      67 oral MRLs. When the substance-specific data permitted, the workgroup departed
      from the default UFs of 10 in 30 specific cases. Specific examples and rationales
      are presented in this paper.

PMID- 8577954
TI  - Guidelines for application of meta-analysis in environmental epidemiology. ISLI
      Risk Science Institute.
AB  - The use of meta-analysis in environmental epidemiology can enhance the value of
      epidemiologic data in debates about environmental health risks. Meta-analysis may
      be particularly useful to formally examine sources of heterogeneity, to clarify
      the relationship between environmental exposures and health effects, and to
      generate information beyond that provided by individual studies or a narrative
      review. However, meta-analysis may not be useful when the relationship between
      exposure and disease is obvious, when there are only a few studies of the key
      health outcomes, or when there is substantial confounding or other biases which
      cannot be adjusted for in the analysis. Recent increases in the use of meta
      analysis in environmental epidemiology have highlighted the need for guidelines
      for the application of the technique. Guidelines, in the form of desirable and
      undesirable attributes, are presented in this paper for various components of a
      meta-analysis including study identification and selection; data extraction and
      analysis; and interpretation, presentation, and communication of results. Also
      discussed are the appropriateness of the use of meta-analysis in environmental
      health studies and when meta-analysis should or should not be used.

PMID- 8577955
TI  - Varied radiologic appearances of pulmonary aspergillosis.
AB  - Pulmonary aspergillosis represents a common, potentially lethal opportunistic
      infection that has four unique forms: allergic bronchopulmonary aspergillosis
      (ABPA), aspergilloma, and invasive and semi-invasive aspergillosis. In
      individuals who are at risk, pulmonary aspergillosis is characterized by a
      spectrum of clinical and radiographic findings that are intrinsically related to
      the status of the immune system or the presence of structural lung disease. ABPA,
      occurring almost exclusively in asthma patients, is characterized
      radiographically by fleeting pulmonary alveolar opacities caused by deposition of
      immune complexes and inflammatory cells within the lung parenchyma. Mucus
      plugging and bronchial wall thickening can be expected in time. Aspergilloma,
      occurring in patients with structural lung disease, typically appears
      radiographically as a focal intracavitary mass and is characterized initially by
      an increase in the wall thickness of a preexisting cavity or cyst. Invasive
      aspergillosis, which occurs primarily in profoundly immunocompromised patients,
      may exhibit nonspecific patchy nodular opacities or lobar-type air-space disease
      in cases with vascular invasion. Computed tomography may reveal a halo or ground
      glass attenuation and is more accurate in the detection of early disease.
      Cavitation often develops with time and typically results in the air crescent
      sign. Semi-invasive aspergillosis is radiographically similar to the invasive
      form but differs in clinical course, being associated with mild immunosuppression
      or chronic illness and typically progressing over the course of months rather
      than weeks.

PMID- 8577956
TI  - Iliopsoas compartment: normal anatomy and pathologic processes.
AB  - The iliopsoas compartment is an extraperitoneal space that contains the greater
      psoas, smaller psoas, and iliac muscles. Many pathologic processes may involve
      the iliopsoas compartment, including inflammatory, hemorrhagic, and neoplastic
      conditions. Psoas muscle infection is usually due to direct extension from
      contiguous structures. With the decreasing incidence of tuberculosis, the
      majority of psoas abscesses now encountered have a pyogenic origin. Hemorrhage
      into the psoas muscle can be spontaneous or secondary to various conditions.
      Neoplastic involvement of the psoas muscle is usually due to contiguous spread
      and is rarely primary. With the refinement of imaging modalities, there has been
      increased recognition of diseases that involve the iliopsoas compartment.
      Although these conditions may look similar radiologically, they can be correctly
      diagnosed by combining the radiologic findings with the clinical history. Biopsy
      is effective in diagnosis of such conditions; aspiration and drainage are
      effective in both diagnosis and therapy.

PMID- 8577957
TI  - Cost shifting--insurance company style.

PMID- 8577958
TI  - Arteriography and interventional therapy for diseases of the hand.
AB  - Because the vessels of the hand are small and very responsive to stimuli,
      arteriography of the hand requires painstaking technique, temperature control,
      and sometimes vasodilator administration to produce sufficient radiographic
      detail. Twenty-five patients underwent arteriography of the hand, which was
      performed from a transfemoral approach to evaluate pathologic changes and the
      possibility of interventional treatment. Production of high-quality images by
      means of attention to technical factors particular to the hand permitted
      recognition of radiographic detail essential to diagnosis. Twelve patients had a
      history of trauma, and five patients had congenital lesions. In eight patients,
      atherosclerotic, vasospastic, or embolic arterio-occlusive disease was diagnosed.
      Interventional radiologic procedures such as thrombolysis, therapeutic
      embolization, and percutaneous transluminal angioplasty are important adjuvant or
      primary management options. Angiography of vascular hand lesions can yield high
      quality diagnostic images when technical factors and physiologic variables are
      maximized. Differentiation between traumatic, congenital, and occlusive lesions
      is then possible.

PMID- 8577959
TI  - MR imaging of nasal masses.
AB  - Magnetic resonance (MR) imaging is useful in evaluating the wide spectrum of
      diseases that cause nasal masses. MR imaging is most helpful in (a) defining
      tumor margins and possible intracranial extension and (b) differentiating tumor
      (which has intermediate, heterogeneous signal intensity on T2-weighted images)
      from concurrent postobstructive sinusitis and other infectious or inflammatory
      masses (which have high, homogeneous signal intensity on T2-weighted images if
      the secretions are well hydrated). The analysis becomes more complicated in cases
      with desiccated and mixed composition secretions. MR imaging also allows
      characterization of very vascular tumors, which show flow voids or marked
      enhancement. Low signal intensity on T1-weighted images and marked low signal
      intensity on T2-weighted images are characteristic of fungal sinusitis, and fat
      within a nasal mass indicates a dermoid or epidermoid cyst. Idiopathic midline
      granuloma, Wegener granulomatosis, and "cocaine nose" manifest as predominantly
      destructive midline masses. Despite the advantages of MR imaging, computed
      tomography remains the preferred imaging modality for evaluating nasal masses
      that contain calcification or originate from bone or cartilage.

PMID- 8577960
TI  - Areas of increased echogenicity in the fetal abdomen: diagnosis and significance.
AB  - Areas of increased echogenicity in the fetal abdomen are defined as abnormally
      bright areas with an echogenicity similar to that of surrounding bones. Such
      areas are encountered in various normal and abnormal processes. When increased
      echogenicity is discovered in the fetal abdomen, a careful search should be made
      for a potential cause. The causes to be considered depend on the location of the
      areas of increased echogenicity, which can be classified as intestinal,
      peritoneal, hepatic, retroperitoneal, and parietal. In each case, vascular,
      ischemic, infectious, tumoral, metabolic, and chromosomal abnormalities should be
      included in the differential diagnosis before considering the finding a normal
      variant. Therefore, in utero detection of fetal abdominal areas of increased
      echogenicity requires a complete sonographic survey of the fetus and placenta
      along with close sonographic follow-up, evaluation of familial factors, and
      testing for possible associated cystic fibrosis, infection, or a chromosomal
      anomaly. The prognosis depends more on the underlying disease than on the extent
      of the increased echogenicity.

PMID- 8577961
TI  - The mammographic spectrum of fat necrosis of the breast.
AB  - Fat necrosis of the breast is a benign condition that most commonly occurs as the
      result of minor breast trauma. The radiographic and clinical significance of fat
      necrosis of the breast is that it may mimic a breast malignancy, requiring biopsy
      for diagnosis. The mammographic appearance of fat necrosis ranges from a lipid
      cyst to findings suspicious for malignancy, including clustered
      microcalcifications, a spiculated area of increased opacity, or a focal mass. The
      changes of fat necrosis may be seen following blunt trauma, cyst aspiration,
      biopsy, lumpectomy, radiation therapy, reduction mammoplasty, breast
      reconstruction with a transverse rectus abdominis myocutaneous (TRAM) flap,
      implant removal, and anticoagulant therapy, as well as in patients without a
      relevant history. Fat necrosis may also be detected mammographically as an
      incidental finding in benign lipomas. It is important to recognize the
      mammographic spectrum of appearances of fat necrosis to avoid unnecessary biopsy
      and to avoid overlooking breast cancer.

PMID- 8577962
TI  - Color Doppler sonography of the thoracic inlet veins.
AB  - Color duplex sonography of the thoracic inlet veins produces a spectrum of normal
      and abnormal findings. These vessels include the internal jugular, innominate,
      subclavian, and axillary veins. Although venography is the traditional means of
      imaging these veins, ultrasound lends itself to assessment of these vessels by
      providing anatomic and hemodynamic information. Advances in gray-scale resolution
      and color Doppler technology permit direct visualization of thrombus, stenosis,
      collateral vessels, catheters, and stents, as well as sensitive spectral waveform
      analysis. Abnormal findings in the thoracic inlet veins include locally elevated
      velocities at stenoses with low velocities peripherally. Thrombus, extrinsic
      compression, and collateral vessels may also produce abnormal findings. Common
      interpretive pitfalls are caused by transducer pressure, deep inspiration, slow
      flow, collateral veins, large-bore catheters, and hemodialysis fistulas. A
      thorough knowledge of the regional anatomy, normal and abnormal waveforms, and
      commonly encountered pitfalls will optimize the accuracy of color duplex
      sonography of the thoracic inlet veins.

PMID- 8577963
TI  - MR imaging artifacts that simulate disease: how to recognize and eliminate them.
AB  - Occasionally, artifacts may simulate pathologic conditions on magnetic resonance
      (MR) images. Motion artifacts especially affect images of the chest and abdomen.
      There are a number of techniques for reducing motion artifacts, including
      respiratory and cardiac gating, k-space phase reordering, gradient moment
      nulling, even echo rephasing, and physical restraints. Aliasing occurs when the
      field of view does not include all of the anatomic structures present in the
      imaged section. Aliasing artifacts can be eliminated by increasing the field of
      view, oversampling, and use of saturation pulses or surface coils. Truncation
      artifacts represent the difference between the original and the reconstructed
      image and can be reduced with data extrapolation algorithms or image filtering.
      Chemical shift artifacts and magnetic susceptibility artifacts are due to a local
      deformity of the magnetic field, resulting in spatial misregistration. Chemical
      shift artifacts are more severe in images acquired with a narrow-bandwidth
      technique; magnetic susceptibility artifacts are more severe in images acquired
      with a long echo time. Pitfalls in the interpretation of MR images can be avoided
      by becoming familiar with the appearances and causes of common MR imaging
      artifacts.

PMID- 8577964
TI  - Guido Holzknecht: astute radiologist.

PMID- 8577965
TI  - History of pediatric radiology in the United States and Canada: images and
      trends.

PMID- 8577966
TI  - Life as a military radiologist: William LeRoy Thompson.

PMID- 8577967
TI  - Teratomas, dermoids, and epidermoids of the head and neck.
AB  - Dermoids and epidermoids are ectoderm-lined inclusion cysts that differ in
      complexity: Epidermoids have only squamous epithelium; dermoids contain hair,
      sebaceous and sweat glands, and squamous epithelium. Both arise from trapped
      pouches of ectoderm, near normal folds, or from failure of surface ectoderm to
      separate from the neural tube. These slowly expanding, unilocular, cystic masses
      may produce only mild symptoms. They commonly occur in the orbit, calvarial
      diploic space, and intracranially (the posterior and middle fossae). They may be
      complicated by rupture leading to chemical meningitis, and dermoids with a
      fistulous tract can become infected. Craniofacial teratomas are true neoplasms
      arising from misplaced embryologic germ cells. They contain a medley of
      heterogeneous tissues, typically reflecting more than one of the three embryonic
      germ layers. They are usually multiloculated masses, often large, with complex
      radiologic characteristics. Craniofacial teratomas may manifest prenatally with
      macrocrania or polyhydramnios, during a difficult delivery, or postnatally as a
      life-threatening mass causing brain herniation, hydrocephalus, respiratory
      distress, or feeding difficulty. In infancy, they can be biologically benign,
      even when their histologic characteristics are immature. Surgery is the treatment
      of choice for all three masses and may be curative.

PMID- 8577968
TI  - Fractal analysis of interstitial lung abnormalities in chest radiography.
AB  - A computerized method for analyzing interstitial lung abnormalities seen on chest
      radiographs was investigated. The method includes two main steps: (a) extraction
      of linear opacities on chest radiographs and (b) calculation of the fractal
      dimension. Extraction of linear opacities uses the processes of four-directional
      Laplacian-Gaussian filtering, binarization, and linear opacity judgment. The
      fractal dimensions in the processed images are then calculated by using the box
      counting algorithm. The accuracy of the computerized method in differentiating
      between normal and abnormal lung tissue was tested on digitized chest radiographs
      (0.175 mm pixel, 10-bit) of 100 randomly selected patients. One hundred regions
      of interest (ROIs) from radiographs of 50 patients with interstitial lung
      abnormalities and 100 ROIs from radiographs of 50 patients with normal lungs were
      analyzed. The fractal dimensions obtained from the ROIs in lungs with
      interstitial abnormalities were significantly higher compared with those from
      ROIs in normal lungs (mean, 1.67 +/- 0.10 vs 1.44 +/- 0.12, respectively; P <
      .001). This result indicates that fractal analysis is useful in distinguishing
      interstitial lung abnormalities from normal lung tissue on chest radiographs.

PMID- 8577969
TI  - Implementation of region-of-interest fluoroscopy by using the road mapping mode
      of a real-time digital radiographic unit.
AB  - In region-of-interest (ROI) fluoroscopy, a filter is used to greatly attenuate
      the x-ray beam outside the ROI and digital image processing is used to equalize
      the displayed brightness. The method is applicable to real-time imaging
      procedures such as vascular interventions for which a high-quality image is
      essential only over an ROI (eg, near the catheter tip), whereas the noise
      degraded periphery may be acceptable for visualizing landmarks. Use of ROI
      fluoroscopy can greatly reduce radiation exposure to the patient and to staff
      while image quality in the ROI is maintained or improved. Exposure reduction
      factors greater than 5 were demonstrated for coil placement in a canine aneurysm
      model by using standard digital angiographic equipment operating in the road
      mapping mode. Potential applications for which future work will determine the
      clinical acceptability of ROI fluoroscopy include many of the highest-dose
      interventional procedures, in addition to general gastrointestinal fluoroscopy.

PMID- 8577970
TI  - Quality control for SPECT systems.
AB  - A comprehensive set of acceptance tests is the basis for an effective quality
      control program. Acceptance tests indicate whether the scintillation camera meets
      published specifications but should also include evaluation of certain parameters
      not specified by the vendor but that can seriously affect image quality. Once a
      camera is "accepted," initial quality control tests serve as a benchmark for
      future measurements. Tomographic systems must be subjected to the same basic
      quality control program as planar cameras. Flood field images must be acquired
      and evaluated daily; spatial resolution must be tested once each week. Less
      frequently, parameters such as multiple-window spatial registration, collimator
      uniformity, system sensitivity, and camera "dead time" should be evaluated.
      Single photon emission computed tomographic systems require additional tests to
      ensure optimum performance. Center-of-rotation calibration and verification of
      detector registration are needed to avoid losses of spatial resolution. Flood
      corrections based on high-count images eliminate residual detector
      nonuniformiaties and correct for subtle collimator defects. Pixel size must be
      calibrated to avoid errors in attenuation correction and distortion when cardiac
      and brain reorientation software is used. Completed clinical studies must be
      checked for unacceptable patient movement and incomplete views. A quality control
      program may be time-consuming, but, from the standpoint of maximum benefit to
      patients and confidence in clinical interpretations, there is no alternative.

PMID- 8577971
TI  - Use of multiplanar reformatted radiographic and digitally reconstructed
      radiographic images for planning conformal radiation therapy.
AB  - A three-dimensional treatment planning system capable of gantry, collimator, and
      table rotations is required for a noncoplanar conformal therapy. Unfortunately,
      such a system is not widely available. A method in which multiplanar reformatted
      radiographic (MPR) and digitally reconstructed radiographic (DRR) images are used
      is presented for conformal treatment of brain tumors. A head phantom containing a
      target volume was scanned on a computed tomographic (CT) simulator. The coronal
      MPR images were digitized on a treatment planning system to create a conformal
      block of the planned treatment field. The DRR images were generated on the CT
      simulator with the setup parameters calculated from the treatment planning
      system. A second set of conformal blocks was generated based on DRR images of the
      fields. The accuracy of the MPR- and DRR-generated blocks was verified on the
      vertex field. The differences between the actual planning target volume and the
      field edges of the MPR and DRR blocks were within +/- 4 mm and +/- 2 mm,
      respectively. The authors conclude that the MPR and DRR images could be
      successfully used to generate conformal blocks and for treatment planning of
      noncoplanar beams in radiation therapy.

PMID- 8577972
TI  - Inside BrighamRAD: providing radiology teaching cases on the Internet.
AB  - The Internet provides opportunities for widely distributing educational materials
      such as teaching files. Since a teaching file is both a tradition and a
      requirement in an accredited diagnostic radiology training program, many of the
      same resources can be committed to designing it for Internet access. The
      advantages include easier availability for the department residents and fellows,
      communication to a wider audience, the opportunity for networking and
      collaboration with other institutions during development, and making information
      available for more rapidly than traditional publications. Since material
      available on the Internet represents an alternative means of publication, all
      cases in an electronic teaching file, as is the case with BrighamRad, should be
      subject to peer review. A successful computer-based teaching file requires
      department-wide commitment of trainees and staff as well as additional expertise
      in multimedia instruction, computer-based graphics and design, image
      manipulation, programming, and database management. Quality efforts take time and
      require continual adaptation and support as technology and the laws and customs
      governing the use of electronically published material evolve. The process should
      be ongoing, and the departmental commitment must be long term and continuous.

PMID- 8577973
TI  - US case of the day. Oriental cholangiohepatitis.

PMID- 8577974
TI  - Pediatric case of the day. Chordoma of the clivus.

PMID- 8577975
TI  - General case of the day. Radiation-induced osteochondroma.

PMID- 8577976
TI  - Chronic pain syndrome: nursing assessment and intervention.
AB  - Chronic pain is a major health problem in the United States. People with chronic
      pain syndrome are a subgroup of patients with chronic pain who experience high
      levels of pain, functional impairment, and depression. Because chronic pain
      syndrome is a complex multidimensional health problem, nurses must use their
      expert knowledge and skills in pain management and in rehabilitation nursing to
      help patients improve their health status and quality of life. This article
      discusses the nursing assessment and management of chronic pain syndrome as well
      as an assessment tool that the author has helped develop.

PMID- 8577977
TI  - Development of a chronic pain assessment tool.
AB  - Research demonstrates that many nurses lack knowledge about pain assessment, the
      differences between acute and chronic pain, and the use of pain rating scales. In
      this article, the authors describe an instrument for evaluating chronic pain, the
      purpose of which is to assess systematically the various dimensions of chronic
      pain and its impact on quality of life. This assessment can establish a baseline
      for developing clients' treatment plans and can be used to evaluate the
      effectiveness of treatment plans. Using this tool can provide an accurate
      multidimensional assessment of clients' chronic pain experiences. The article
      also discusses recommendations for other applications of the tool.

PMID- 8577978
TI  - Effects of a multimodal pain rehabilitation program: a pilot study.
AB  - The purpose of this pilot study was to examine the effects of a multimodal pain
      rehabilitation program on pain perceptions, opioid usage, activity, down time,
      sleep, and role function status of 23 chronic pain patients. Data were collected
      at the start of the program, at the program's completion, and again during a
      follow-up period (3-11 months afterwards). At the end of the program, patients
      reported a significant reduction in pain levels, opioid usage, and hours of
      disturbed sleep. During the follow-up period, patients continued to report
      significant improvements in activity and role functions as well as significant
      reductions in opioid usage, sleep disturbance, and down time. These findings
      provided encouraging preliminary evidence that multimodal pain rehabilitation
      programs for chronic pain patients may be effective in pain management and
      functional restoration.

PMID- 8577979
TI  - Caregivers of people with multiple sclerosis: a survey in New Zealand.
AB  - A survey carried out in the Manawatu and Wanganui area of New Zealand was
      designed to locate all those known to have multiple sclerosis; as part of the
      research, 31 primary caregivers (20 males, 11 females) of MS patients in the
      study were interviewed to gain information about their roles, self-defined tasks,
      and life situations.

PMID- 8577980
TI  - Intimacy and rheumatic diseases.
AB  - During patient education, the issue of intimacy, as much as medications and the
      disease process, needs to be addressed by the rehabilitation nurse. Adequate
      information usually is not provided because patients, nurses, and physicians may
      avoid discussing sexual matters. Healthcare professionals may feel uncomfortable,
      may lack specific knowledge about sexual relationships, or may be too task
      oriented. In this article, the author explains that intimacy involves more than
      just sexual intercourse and explores the role that intimacy plays in how a
      patient copes with a chronic illness such as a rheumatic disease.

PMID- 8577981
TI  - What shall we do about Phil?

PMID- 8577982
TI  - The painful truth about pain management.

PMID- 8577983
TI  - Understanding work group culture on rehabilitation units: the key to facilitating
      group innovation and promoting integration.
AB  - Understanding work group culture is essential for the smooth running of today's
      complex rehabilitation units. Failure to understand a unit's culture can impede
      necessary care delivery innovations and impair group integration. This article
      describes the phenomenon of work group culture and offers suggestions for
      assessing and understanding a given unit's culture. It also illustrates how an
      understanding of work group culture can facilitate innovation by reframing and
      tailoring a change and can promote integration by helping nurses adjust to a new
      unit.

PMID- 8577984
TI  - Mechanisms of T-cell-induced allotypic suppression of mouse IgG2a(b) and of
      tolerance acquisition to this allotype.

PMID- 8577985
TI  - Lymphocytes in a model ecosystem.

PMID- 8577986
TI  - Natural autoantibodies: the other side of the immune system.

PMID- 8577987
TI  - T-cell activation, anergy and immunomodulation by molecules of viral, fungal and
      vegetal origin.

PMID- 8577988
TI  - Towards a vaccine against asexual blood stage infection by Plasmodium falciparum.
AB  - In this paper, we will summarize the progress obtained in the malaria vaccine
      project developed by the Institut Pasteur groups interacting through the
      International Network of Pasteur Institutes over the last fifteen years. While
      trying to follow the progress in scientific and technological concepts and
      methodologies, the basic approach was still essentially the same as that followed
      by Pasteur and his acolytes to try to artificially reproduce the natural
      processes that lead to the development of immunity to infection and disease. A
      longitudinal study of two villages from the Sine Saloum area of Senegal, Dielmo
      and N'Diop, conducted in recent years by teams of the Institut Pasteur of Dakar,
      Senegal, in collaboration with the local ORSTOM malaria unit has led to the
      detailed analysis of the natural acquisition of premunition against Plasmodium
      falciparum malaria in endemic areas. The Saimiri model developed at the Pasteur
      Institute in Cayenne, was an important step forward in terms of studies on the
      mechanisms of action of protective antibodies and on vaccinations assays. If we
      accept the conclusions of the Pasteur groups' research on the experimental
      primate model and on the development of natural immunity (premunition) in highly
      endemic areas, the main inhibitor of progress in vaccine development is our poor
      understanding of the regulation of the immune response. Therefore, the general
      approaches that were followed for vaccine development must now be further
      explored using the continually developing tools of immunology and molecular
      biology, to elucidate regulations of the immune responses to the parasite, and
      identify the molecular mechanisms used by the parasite to generate and change
      antigen specificities.

PMID- 8577989
TI  - The structure of the antigen-binding site of immunoglobulins and T-cell
      receptors.

PMID- 8577990
TI  - Molecular mechanism of T-cell activation: role of protein tyrosine kinases in
      antigen receptor-mediated signal transduction.

PMID- 8577991
TI  - Thoughtful cruises in oceans of peptides and T cells.

PMID- 8577992
TI  - Simple developmental programs of gene expression and cellular composition of
      lymphoid organs at the origin of natural tolerance.
AB  - Self-tolerance is acquired in the embryonic/perinatal period, but new lymphocytes
      (that will have to distinguish between self and nonself) continue to be produced
      throughout life, after both self and nonself are present. This makes it
      impossible for natural tolerance to rely on recessive mechanisms. Recent
      observations on "dominant tolerance" have led to the hypothesis that natural
      tolerance is established as a consequence of simple developmental programs for
      gene expression and cellular composition of primary lymphoid organs. In
      development, the cellular composition of the thymus is predominantly epithelial,
      allowing for the positive selection and activation of "high avidity" self
      reactive T cells that are not deleted because antigen presentation by
      haemopoietic cells is limiting. Such T cells, activated in that environment,
      display effector functions of a regulatory type that are maintained in the
      periphery upon restimulation by tissue peptides shared with the thymic
      epithelium. Recent thymic emigrants with specificity for tissue-specific antigens
      that are absent from the thymus will first encounter their ligands in the context
      of the "regulatory cell" recognition of ubiquitous peptides and are thus
      recruited into similar regulatory activities. In contrast, thymic emigrants with
      specificity for nonself antigens (absent during the perinatal period) are not
      activated intrathymically, reach the periphery as resting cells, and move out of
      the time window of susceptibility to functional recruitment. These will react "de
      novo" upon encounter of the respective antigens and will acquire the class of
      effector functions determined by the peripheral microenvironment in which they
      are activated. This strategy, which explains the thymic dependence of peripheral
      tissue-specific tolerance, may be re-enforced by developmental restrictions in
      cytokine gene expression, and it will ensure the establishment and maintenance of
      T-cell tolerance through the dynamic storage of a distributed memory of the
      embryonic self. B lymphocytes that are produced in the embryonic/perinatal period
      characteristically rearrange and express a few V-genes very predominantly. These
      V-genes encode antibodies with unique properties of "connectivity" to other V
      regions, making it possible to establish a network that limits clonal expansions
      and/or terminal differentiation to antibody production. Self-reactive B cells are
      thus recruited into such a network which, by contributing to the molecular
      environment of the body and to the selection of emergent repertoires, leads to
      deletion of connected cells and to the "normalization" of the adult antibody
      repertoires. Natural autoantibody repertoires in the adult are thus recursively
      maintained, stable and continuously adjusted to the thresholds of single cell
      deletion and to the alterations in the body composition. The activity of self
      specific regulatory T cells contributes to limiting clonal expansion and
      inhibiting somatic mutation of self-reactive B cells. This model explains a
      number of observations that were not included in the "clonal" and "recessive"
      tolerance views, and offers suggestions on mechanisms in physiological
      autoimmunity and pathology.

PMID- 8577993
TI  - HPr: heteromorphous protein.

PMID- 8577994
TI  - Molecular characterization of rhizosphere and clinical isolates of Burkholderia
      cepacia.
AB  - Four Burkholderia cepacia strains isolated from the rhizosphere and pathological
      samples of infected human patients were characterized at the molecular level by
      different methodologies, including the determination of 16S ribosomal rDNA
      sequence, restriction endonuclease analysis of total DNA, random amplified
      polymorphic DNA fingerprinting and Southern hybridization with gene probes for
      nitrogen fixation and siderophore synthesis. The results indicate that the four
      strains cluster together within genus Burkholderia, but differ from one another.
      The DNA from the four strains hybridized to the nifA gene probe from Klebsiella
      pneumoniae, and an appreciable homology with the nifHDK structural genes of
      Azospirillum brasilense was demonstrated for one rhizosphere strain. Although the
      four isolates produced an ornibactin-like siderophore, they did not give
      hybridization with the pvdA probe for hydroxamate biosynthesis from Pseudomonas
      aeruginosa.

PMID- 8577995
TI  - The genus Methylophaga, a new line of descent within phylogenetic branch gamma of
      Proteobacteria.
AB  - The genus Methylophaga with two species, M. marina and M. thalassica, comprises
      halophilic methylotrophic bacteria. These organisms utilise C1 compounds through
      the ribulose monophosphate pathway and are unable to grow on methane. Nearly
      complete 16S rRNA sequences were obtained for both Methylophaga species by
      directly sequencing the amplified 16S rRNA gene. These sequences were compared
      with published 16S rRNA sequences of methylotrophic strains and a large number of
      marine bacterial strains including several members of the alpha, beta and gamma
      subclasses of Proteobacteria. Phylogenetic trees were inferred using both
      parsimony and distance matrix methods. Each topology was analysed by bootstrap.
      The genus Methylophaga was found to be clearly separated from other
      methylotrophic bacteria and formed a distinct branch within the gamma subclass of
      Proteobacteria.

PMID- 8577996
TI  - Invasion of cultured human cells by Streptococcus pyogenes.
AB  - The invasive capacity of streptococcal strains belonging to groups A and B was
      evaluated by infecting human epithelial and endothelial cells and monitoring the
      number of viable intracellular bacteria at different times postinfection. All
      strains tested entered eukaryotic cells (HeLa, HEp2 and HUVE), with Streptococcus
      pyogenes exhibiting a higher invasion efficiency than group B streptococci (GBS).
      No intracellular multiplication was observed, and GBS remained viable 24 h
      postinfection, whereas S. pyogenes were gradually killed. We found that
      cytochalasin D almost completely inhibited internalization of all bacterial
      strains, whereas colchicine had no effect, indicating that host microfilaments
      play a major role in bacterial internalization. Moreover, the use of the
      lysosomotropic agent ammonium chloride enabled us to demonstrate that a pH
      increase in the intracellular vesicles did not affect streptococcal entry. These
      results were documented by electron microscopic observations which revealed the
      different steps in the invasion pathway, including a fusion event between
      phagosomes containing S. pyogenes and lysosomes.

PMID- 8577997
TI  - Variations in DNA concentrations significantly affect the reproducibility of RAPD
      fingerprint patterns.
AB  - The influence of the DNA concentration was tested using two different primers and
      nine DNA samples. Major modifications in the DNA banding pattern were apparent
      between successive dilutions. Such differences could be explained by concomitant
      changes in three different molecular conditions: the presence of perfect priming
      sites, the amplification of rare sites and the existence of mismatch annealing
      events. At low DNA concentrations (less than 1 pg/microliter), molecular events
      occurred at random and had a direct consequence on the reproducibility of RAPD
      profiles. At the appropriate DNA concentration (between 100 ng/microliters and 10
      pg/microliters), reproducibility was adequate at a given concentration, but RAPD
      profiles differed from one dilution to another. These observations demonstrate
      the usefulness of the bis-benzimide method for quantification of DNA extracts.

PMID- 8577998
TI  - Heterogeneity of Brucella abortus lipopolysaccharides.
AB  - This work demonstrates that Brucella lipopolysaccharide (LPS) preparations are a
      family of related molecules which display heterogeneity not only at the level of
      the O polysaccharide, but also at the core oligosaccharide and the lipid A.
      Sodium dodecyl sulphate/polyacrylamide gel electrophoresis and Western blotting
      showed that LPS from Brucella strains displayed molecular weight and antigenic
      heterogeneity. Smooth-type LPS (S-LPS) from B. abortus demonstrated three broad
      high-molecular-weight bands corresponding to S-LPS, and a low-molecular-weight
      band corresponding to O antigen lacking rough-type LPS (R-LPS). B. abortus R-LPS
      displayed four bands in increasing proportions as the molecular weight
      diminished. Immunodetection on high-performance thin-layer chromatography (HPTLC)
      with monoclonal antibodies (mAb) showed that R-LPS displayed three diffuse bands.
      HPTLC of O polysaccharide revealed two fast migrating bands recognized by
      antibodies. Gel chromatography and HPTLC analysis of core oligosaccharides from R
      LPS demonstrated molecular weight heterogeneity as well as heterogeneous banding
      pattern, with no obvious correspondence between the two profiles. Immunodetection
      of lipid A on HPTLC plates revealed two major and three minor bands. Reactivity
      with mAbs suggested that regardless of the lipid A heterogeneity the basic
      structure of lipid A backbone is maintained.

PMID- 8577999
TI  - Combination of biotyping and electrophoretic patterns of esterases for
      differentiation of nosocomial Serratia marcescens strains.
AB  - A total of 292 Serratia marcescens strains isolated in seven Belgian hospitals
      between 1986 and 1992 were submitted to both biotyping by carbon source
      utilization and esterase electrophoresis typing. The strains were assigned to 11
      biotypes (290 isolates) or were auxotrophic (2 isolates), whereas the various
      electrophoretic patterns of their esterases produced 54 zymotypes. The two typing
      methods correlate well, since biotypes embraced more than one zymotype, while
      each zymotype was restricted to a single biotype. Esterase electrophoretic
      patterns represent a potent marker for delineating outbreaks of nosocomial
      infections, whereas biotyping appears to be an appropriate method for screening
      of strains.

PMID- 8578000
TI  - DNA fingerprinting by random amplified polymorphic DNA and restriction fragment
      length polymorphism is useful for yeast typing.
AB  - Random amplified polymorphic DNA (RAPD) analysis was applied to genomic DNA from
      nineteen yeast strains belonging to the genera Saccharomyces and
      Zygosaccharomyces. Results obtained with five primers indicated that this
      technique is a powerful tool for yeast differentiation and identification. The
      data were consistent with those derived from restriction fragment length
      polymorphism (RFLP) using two S. cerevisiae DNA probes. We conclude that RAPD
      fingerprinting, combined with the analysis of RFLP, can provide unambiguous type
      assignment in yeasts.

PMID- 8578001
TI  - An experimental study of conductive heating using a concentric double-electrode
      applicator.
AB  - With hyperthermia for treatment of superficial tumors in mind, a prototype
      applicator with two electrodes arranged concentrically on a disk was designed for
      efficient local heating, and a basic heating test was carried out. Frequencies as
      low as 200 kHz were used in order to simplify the configuration of the power
      device. The applicator consists of two electrodes, a circular inner electrode and
      another looped outer electrode, arranged concentrically. Water was passed through
      the applicator as a cooling mechanism; it was placed in direct contact with the
      target tissue to be heated and then charged with electricity. In the heating test
      using a phantom, oval hot spots were noted below the inner electrode. Using
      cooling water at 3 degrees C and 8.2 W, an isothermal line of 45 degrees C was
      located at a 5-mm radius circle around the central axis with 9 mm depth. A
      similar temperature distribution map was obtained in heating tests on the thigh
      muscle of a mongrel adult dog. The temperature distribution maps obtained from
      these tests corresponded closely with the results of theoretical analysis carried
      out according to the finite-element method. Since a comparatively low frequency
      was employed for this applicator the power device was simplified, which made
      adequate heating possible with low electric power. The temperature distribution
      map indicated that efficient local heating of superficial tumors could be
      achieved.

PMID- 8578002
TI  - Effects of oxytocin on the function and morphology of the rat adrenal cortex: in
      vitro and in vivo investigations.
AB  - The effects of oxytocin (OX) on the function and morphology of the rat adrenal
      cortex were studied in vivo and in vitro. OX exerted a potent stimulatory action
      on basal, but not 10(-8) M ACTH-stimulated corticosterone (B) secretion of
      dispersed rat inner (zona fasciculata and zona reticularis) adrenocortical cells
      (maximal effective concentration: 10(-9) M); in contrast, at higher
      concentrations (10(-7)/10(-6) M) OX inhibited maximally ACTH-stimulated B output.
      A single subcutaneous (s.c.) injection of 1.2 nmol/100 g body weight OX resulted
      in a long-lasting (up to 12 h) rise in plasma B concentration (PBC). The
      prolonged administration of OX (daily s.c. injections of 0.6 or 1.2 nmol/100 g
      for 10 days) caused a marked lowering in the adrenal weight and volume of all
      adrenocortical zones, that in turn was due to a decrease in the number of their
      parenchymal cells; however, the average volume of inner adrenocortical cells was
      significantly increased. Basal PBC was lowered, but its response to ether stress
      was unchanged in comparison with control rats. Prolonged OX treatment did not
      change B secretion by adrenal slices, but it markedly raised that of dispersed
      inner adrenocortical cells. Our present findings clearly show that the effects of
      OX on the adrenal cortex depend on the experimental model employed (in vitro
      versus in vivo) and the duration of treatment (acute versus chronic). Taken
      together they allow us to conclude that OX exerts an acute direct stimulatory
      effect on the rat adrenal cortex, and a chronic inhibitory one, that at least in
      part could be due to the interference of OX with the mechanism(s) of
      intracellular transduction of the ACTH secretagogue signal.

PMID- 8578003
TI  - Quantitative analysis of angiogenesis and growth of bone: effect of indomethacin
      exposure in a combined in vitro-in vivo approach.
AB  - Nonsteroidal anti-inflammatory agents have been used experimentally and
      clinically to suppress a variety of physiological events, including angiogenesis
      and formation of bone. The exact mechanisms by which indomethacin alters skeletal
      tissue generation are unknown, due in part to methodological limitations. By the
      use of an organ culture assay and an animal model using intravital microscopy in
      mice bearing dorsal skinfold chambers, the effect of indomethacin on growth and
      angiogenesis of neonatal femora was characterized over 16 days. In both assays,
      femora significantly elongated with time (P < 0.05). The in vitro growth rate was
      more rapid than in vivo and dependent on the serum concentration, culture medium
      and age of mice. Although enhancing the serum content promoted cellular
      proliferation in organ culture, it dose-dependently suppressed femoral
      elongation, leading at 20% fetal calf serum to growth rates identical to those
      observed in vivo. Indomethacin supplementation (2 and 10 mg l-1) significantly
      accelerated longitudinal femoral growth in organ culture (P < 0.05), whereas in
      vivo indomethacin (2 mg kg-1) did not modulate either angiogenesis or elongation
      of bone. Our in vitro data propose a central role of serum in the regulation of
      bone formation. Although indomethacin altered femoral growth in vitro, our
      findings do not suggest that indomethacin suppresses angiogenesis or growth of
      bone in vivo. The complexity of physiological events in vivo may be obscuring a
      detectable effect.

PMID- 8578004
TI  - Amylin immunoreactivity in the rat trachea and characterization of the
      interaction of amylin and somatostatin on airway mucus secretion.
AB  - Amylin is a peptide containing 37 amino acids that is mainly expressed in
      pancreatic B-cells and cosecreted with insulin. It is the major component of the
      islet amyloid typically found in non-insulin-dependent diabetes mellitus. The
      amylin mRNA is present in RNA isolated from lung, and amylin receptors have been
      detected in lung membranes. Recently, amylin was shown to be a potent stimulator
      of airway mucus secretion. In this study, we characterized the site of amylin
      expression in rat trachea using a highly specific antiserum and the functional
      interaction of amylin with somatostatin-14 in mucus secreting cells. Amylin-like
      immunoreactivity is present in epithelial cells of submucous gland acini. The
      expression pattern varies, since some acini showed strong staining while others
      were negative. In addition, some columnar cells of the tracheal lining epithelium
      are strongly stained. Amylin applied submucosally is a potent stimulator of
      airway mucus secretion. Somatostatin inhibits this effect. Amylin may influence
      airway mucus secretion by paracrine and endocrine mechanisms, and our data
      suggest that amylin and somatostatin belong to the increasing number of peptides
      that are known to influence airway function.

PMID- 8578006
TI  - Infection of cultured human intestinal cells by monkey RRV and human Wa rotavirus
      as a function of intestinal epithelial cell differentiation.
AB  - Rotaviruses display in vivo a specific tropism for enterocytes of the small
      intestine. We examined here the infection of cultured human intestinal epithelial
      Caco-2 cells by rhesus monkey rotavirus (RRV) and human Wa rotavirus. The maximal
      infection of these cells was obtained when trypsin was present both in the viral
      inoculum before adsorption to the cells and in the culture medium during the
      course of cell infection. Since the differentiation process of Caco-2 cells in
      culture closely mimics in vivo differentiation of enterocytes along the crypt
      villus axis, cell infection by RRV and Wa rotavirus was examined as a function of
      cell differentiation. We showed that RRV and Wa rotavirus can infect equally well
      both undifferentiated and differentiated Caco-2 cells.

PMID- 8578005
TI  - Possible role of bovine immunodeficiency virus in bovine paraplegic syndrome:
      evidence from immunochemical, virological and seroprevalence studies.
AB  - Bovine paraplegic syndrome (BPS) is a debilitating cattle disease of unknown
      origin that is characterized by leukocytosis, lymphocytopenia and monocytopenia.
      The major clinical signs are difficulties in locomotion affecting hind limbs,
      hypoalgesia in the hind quarters, posterior paralysis and death within 72 to 96
      hours after recumbency. To investigate the aetiological basis of BPS, we examined
      a possible association of the syndrome with infection by bovine immunodeficiency
      virus (BIV), a lentivirus implicated in immune system dysfunction and central
      nervous system lesions in cattle. Serum samples (n = 1,278) were collected from
      both healthy and BPS-prevalent cattle herds in Venezuela, and organ extracts were
      prepared from euthanized animals (n = 11) suspected of having BPS. Sera were
      analysed for reactivity to recombinant BIV and bovine leukaemia virus gag
      precursor proteins by immunoblot procedures. Serum reactivity to BIV ranged from
      12 to 66% between groups of BPS prevalent herds. The percentage of samples
      reactive to BLV antigen was much lower (2 to 17%). Rabbits inoculated with
      extracts from BPS-afflicted animals exhibited an anamnestic immune response to
      BIV antigens as well as the presence of BIV gag antigens in their tissues. We
      present evidence for a possible association between BPS disease and a viral agent
      related to BIV. The role of BIV, in combination with malnutrition, in BPS is
      discussed.

PMID- 8578007
TI  - Preferential selection of specific rotavirus gene segments in coinfection and
      multiple passages with reassortant viruses and their parental strain.
AB  - We previously reported non-random selections of human rotavirus (HRV) Wa genes 2
      and 5 in reassortant formation between HRV strains Wa and HN126 under selection
      pressure with neutralizing monoclonal antibodies. In order to study whether or
      not these genes are preferentially selected in the genetic background of a
      parental strain HN126 in vitro without selection pressures, coinfection and
      multiple passage experiments were performed between HN126 and one of three
      reassortants, C1, C1T and C1F; C1 possessed genes 2 and 5 derived from Wa and the
      other genes derived from HN126, while C1T and C1F were single gene reassortants
      having Wa gene 2 or Wa gene 5 in the genetic background of HN126, respectively.
      When MA-104 cells were coinfected with the same infectious units of HN126 and C1,
      Wa genes 2 and 5 of reassortant C1 became predominant within 10 repeated
      passages, although Wa gene 5 was selected more preferably than Wa gene 2. Similar
      results were obtained under different experimental conditions in which different
      doses of parental strains or different type of cells were used. Also, in
      coinfections of MA-104 cells with HN126 and C1T, or HN126 and C1F, Wa gene 2 or
      Wa gene 5 became predominant at the sixth passage. Analysis of viral growth
      curves indicated that two reassortants, C1 and C1F, replicated to a titre higher
      than HN126, while no difference in viral growth was observed between C1T and
      HN126. These results indicated that in the genetic background of HN126, Wa gene 5
      might provide viruses with a growth advantage compared with its HN126
      counterpart, while Wa gene 2 might be preferentially selected into reassortant
      clones through its greater functional capacity for assortment during viral
      replication.

PMID- 8578008
TI  - Sequence characterization of the adenovirus 31 fibre and comparison with
      serotypes of subgenera A to F.
AB  - The amino acid sequence of the adenovirus type 31 (subgenus A) fibre polypeptide
      was deduced from the nucleotide sequence of the fibre gene. The analysed peptide
      sequence showed an organization consistent with the structural domains described
      for other adenoviruses: an amino-terminal tail region, an intervening shaft
      region and a carboxy-terminal knob. The AV31 fibre shaft displayed 20 repeats of
      the 15-amino-acid segments in the shaft domain, which agreed with the reported
      length of the fibre. The predicted AV31 fibre polypeptide sequence was compared
      to fibre polypeptides of serotypes representing subgenera A to F. As expected,
      AV31 and AV12, both belonging to subgenus A, showed the highest overall homology
      (75.4%). When comparing the AV31 fibre to the fibre polypeptides of subgenera B
      to F, AV31 and AV41 (subgenus F) shared the highest overall homology (35.3%),
      followed by AV40 (34.8%). The lowest overall homology (20.3%) was found for the
      AV31 and Av3 fibres (subgenus B). From the data presented, it could be suggested
      that AV31 is more closely related to the enteric viruses of subgenus F than to
      the other adenoviruses analysed. Comparing the fibre polypeptides of 14
      adenovirus serotypes, 10 conserved amino acid sequences were detected, 5 of which
      were in the knob region. Since the fibre knob interacts with the host cell during
      infection, these conserved amino acids might be important for virus attachment.
      The gastroenteritis-causing adenoviruses AV40 and AV41 shared 3 additional
      conserved amino acid residues with AV31 and AV12 in the knob region.

PMID- 8578009
TI  - Nested RT-PCR for detection of sandfly fever virus, serotype Toscana, in clinical
      specimens, with confirmation by nucleotide sequence analysis.
AB  - A single tube, reverse transcriptase/polymerase chain reaction (RT-PCR) was
      developed and evaluated for detecting a 400-bp product of the small RNA of
      sandfly fever virus, serotype Toscana (TOS). For more sensitive detection of
      genomic TOS RNA, a nested PCR amplifying a 243-bp cDNA within the RT-PCR product
      was established. Nucleotide sequence analysis of first- and second-round PCR
      products using the dideoxy cycle sequencing technique confirmed a previously
      published sequence of the TOS reference strain (ISS. Phl.3). By nested PCR,
      genomic TOS RNA was amplified from two consecutive sera taken 3 and 7 weeks after
      the onset of illness in one patient, and from CSF of a second patient obtained at
      the onset of meningitis. Authenticity of amplified PCR products was confirmed by
      nucleotide sequence analysis, revealing a sequence identical to the TOS reference
      strain. RT-PCR and nested PCR are useful for laboratory diagnosis and studies of
      the molecular epidemiology of TOS infection.

PMID- 8578010
TI  - Detection of hepatitis C virus RNA by a reliable, optimized single-step reverse
      transcription polymerase chain reaction.
AB  - A single-step reverse transcription polymerase chain reaction (SRT-PCR) method
      was optimized for hepatitis C virus (HCV) RNA detection. Extraction procedures by
      proteinase K and guanidinium isothiocyanate gave similar results. The optimal
      MgCl2 concentration for the SRT-PCR method was 2 mM with 10 units of superscript
      M-MLV RNase H-reverse transcriptase and 1 unit of Taq polymerase. Shorter PCR
      cycling steps gave a 10-fold-increased PCR product compared with longer cycling
      steps. Twenty-five anti-HCV-positive sera from chronic hepatitis C patients were
      positive with SRT-PCR, whereas only 17 out of 25 were positive by dissociated RT
      and PCR (dRT/PCR). Specificity was assessed by twenty negative controls. SRT-PCR
      was 5-fold more sensitive (5 HCV RNA copies per assay) than dRT/PCR with an HCV
      RNA transcript. Our SRT-PCR method for HCV RNA detection appears fully adapted
      for routine use in a medical virology laboratory.

PMID- 8578011
TI  - Haemagglutination by rotaviruses in relation to VP4 genotypes.

PMID- 8578012
TI  - Lung function changes and exercise-induced ventilatory responses to external
      resistive loads in normal subjects.
AB  - AIM: The aim of this study was (1) to assess the value of common lung function
      variables in the follow-up of patients with obstructive lesions of the larynx and
      trachea and (2) to study the respiratory response to progressive upper airway
      stenosis at rest and during exercise. METHODS: Lung function tests, including
      vital capacity (VC), residual volume (RV), total body plethysmographic resistance
      (RT), specific body plethysmographic resistance (Rs), total body plethysmographic
      resistance at low inspiratory/expiratory flows (Rlo), forced expiratory volume in
      1 s (FEV1), peak expiratory flow rate (PEF), peak inspiratory flow rate (PIF),
      maximum expiratory flow at 50% VC(MEF50) and maximum inspiratory flow at 50%
      VC(MIF50) were performed in 14 normal subjects with added external resistive
      loads (inner diameter of circular orifice: 15, 10, 8, 6 mm; equivalent to surface
      areas of 177, 79, 50 and 28 mm2, respectively), applied in random order. The
      relative sensitivity of each variable to detect a stepwise decrease in orifice
      size by evoking 'relevant' obstructive responses was calculated. In addition,
      ventilatory and gaz exchange responses to loaded breathing (10-, 8- and 6-mm
      orifices, randomly inserted) during steady-state bicycle exercise (80 and 160 W)
      were assessed in a subgroup of 10 subjects. RESULTS: The gradual increase of
      external load did not influence static lung volumes (VC, RV). MEF50/MIF50 (1.63
      +/- 1.03 at baseline) remained essentially unchanged, consistent with the rigid
      nature of the obstructive device. PEF was superior in reproducing the transition
      from unloaded over mild (15 mm) and moderate (10 mm) to high grade (8 mm) central
      obstruction. Except for mild loads, PIF was equal in sensitivity to PEF. At high
      grade (8 mm) and severe loads (6 mm), no difference in sensitivity could be
      established between RT, Rs, FEV1, PIF and PEF. However, they were all superior to
      Rlo. Compared to unloaded breathing, ventilation across the 10- and 8-mm orifices
      at both rest and exercise produced a continuous significant increase in oxygen
      uptake (VO2). Respiratory rate (RR) fell, and a simultaneous enlargement of tidal
      volume (VT) was observed to maintain or even enhance minute ventilation (VE).
      However, ventilation across the 6 mm orifice was associated with a substantial
      decline in VO2, VCO2 and VE relative to the preceding load (8 mm) CONCLUSIONS: It
      is suggested that the experimental use of inspiratory and expiratory extrinsic
      loads can mimic rigid obstructive lesions of the larynx and trachea. Among all
      conventional lung function values, PEF and, to a certain degree, PIF, seem to be
      the best suitable follow-up parameters to assess airway mechanics before and
      after surgical/endoscopic procedures. Upper airway stenosis involving surface
      areas of no more than 50 mm2 can be overcome using adequate respiratory
      compensation. But any additional narrowing below this limit will result in
      hypoventilation, inappropriate oxygen uptake and retention of CO2. Thus,
      experimental evidence indicates that laryngotracheal obstruction within a
      critical range below 50 mm2 surface area (diameter of circular orifice < 8 mm)
      compromises respiratory efforts enough to be of clinical importance.

PMID- 8578013
TI  - Ventilatory and pulmonary vascular responses to acute hypoxia are nonuniform in
      healthy man.
AB  - The present study was undertaken to examine the pulmonary vascular and
      ventilatory responses to acute hypoxia in healthy individuals. Pulmonary
      hemodynamics and minute ventilation (VE) were serially measured during inhalation
      of 13% O2 for 15 min. There was a wide variability in the pulmonary vascular
      response to acute hypoxia, and a significant negative correlation between the
      initial increase in VE after the start of hypoxia (delta VE) and the percent
      increase in mean pulmonary arterial pressure (r = -0.646; p < 0.01). The fall in
      arterial oxygen tension significantly decreased in response to an increase in
      delta VE. These results support the view that a blunted ventilatory response to
      acute hypoxic stimulation enhances alveolar hypoxia, thereby favoring the
      constriction of pulmonary vasculature. Thus, our results suggest that the
      ventilatory response to acute hypoxia plays a significant role in the pulmonary
      vascular response to acute hypoxia.

PMID- 8578014
TI  - Pharmacokinetics and pharmacodynamics of beta 2-agonists (in the light of
      fenoterol).
AB  - As an example of beta 2-agonists fenoterol was used in this study on 27 patients
      with chronic obstructive airways diseases (COAD). After refraining from any kind
      of bronchodilator during 12 h the patients were given the drug in a crossover
      design in three groups. Using aerosol inhalation, intravenous route and nasal
      instillation we measured the response of airway resistance, intrathoracic gas
      volume and fenoterol plasma concentrations. The plethysmographic measurement of
      airways resistance (Rt) and intrathoracic gas volume showed comparable results of
      bronchodilation (at different dosages) for each of the routes. Even the onset of
      action was nearly the same with all the different routes. The amount of
      bronchodilatation was in the range of 59% of the initial Rt values. The duration
      of bronchodilatation was much longer after metered dose inhalers (MDI) inhalation
      ( > 4 h) than after intravenous routes. The duration after nasal administration
      was in between. The infusion maintains its effect only as long as the infusion is
      given. The bronchodilation response induced by fenoterol reaches the same values
      with different routes of administration and depends on the amount of decrease of
      airway obstruction. The highest plasma concentrations were reached with the
      intravenous boluses. Immediately after injection the concentration decreased
      rapidly. The maximum plasma concentrations after MDI were around 20% of that
      after the intravenous route for the same bronchodilatation. The heart rate is a
      function of the plasma concentration. At low concentrations such as after aerosol
      inhalation of 200 micrograms the influence on the heart rate is not significant.
      After aerosol inhalation the effect at the receptor can be calculated to be > 7
      times stronger than seen from any plasma concentration after intravenous
      administration. It is assumed that there are structures near the beta 2
      bronchodilator receptor which are responsible for the long-lasting effect that is
      observed only after aerosol inhalation. These depot structures cannot be reached
      from the plasma in concentrations needed under in vivo conditions. Loss of these
      structures shortens the duration of the bronchodilator effect. In respect to
      effect/side effect relationship, more frequent administration of smaller doses
      may be the best method for administering beta 2-agonists as aerosols in patients
      with COAD. For many patients with severe forms of this disease, individual
      optimal dosage with MDI has to be defined following repeated measurements of the
      airway obstruction so as to achieve the best possible bronchodilatation.

PMID- 8578015
TI  - A way to select on clinical grounds patients with high risk for pulmonary
      embolism: a retrospective analysis in a nested case-control study.
AB  - We studied 196 patients with suspicion of pulmonary embolism (PE), subsequently
      confirmed in 98 by positive pulmonary angiography and excluded in 98 by normal or
      near-normal perfusion lung scan. Patients had a clinical questionnaire for
      history, and, soon after. a radiograph, blood gas analysis, and an ECG. Clinical
      and instrumental signs were matched in patients with confirmed and unconfirmed PE
      to find those more frequent in embolic patients and, thus, more characteristic of
      PE. The following were: previous PE, immobilization and thrombophlebitis (p <
      0.05); dyspnea and cough (p < 0.05); enlarged descending pulmonary artery (DPA),
      enlarged right heart, pulmonary infarction, Westermark sign (p < 0.001), and
      elevated diaphragm (p < 0.05); hypoxemia. No ECG sign was more frequent in PE.
      Thereafter, all variables were processed separately with a logistic multiple
      regression analysis and those significantly associated to PE were tested in a
      final logistic model that was able to predict the actual result of angiography or
      scintigraphy; accordingly, previous PE, immobilization, thrombophlebitis,
      enlarged DPA, pulmonary infarction, Westermark sign, hypoxemia were significantly
      associated with a high risk of PE (from 2.8 to 15 times greater than in patients
      without these signs). Therefore, we may conclude that clinical assessment and
      noninvasive tests may help to detect patients at higher risk for PE where heparin
      coverage should be started while waiting for conclusive diagnostic procedures.

PMID- 8578016
TI  - Influence of estrogen replacement therapy on airway reactivity.
AB  - The effect of estrogen on smooth muscle in various organs is unpredictable.
      Little is known about the effect of estrogen on respiratory tract smooth muscle,
      particularly in humans. In the present study we used the histamine challenge test
      (HCT) to assess the effect of estrogen replacement therapy (ERT) on airway
      reactivity in postmenopausal women who did not suffer from respiratory disease.
      Thirty-six women who were undergoing treatment at the postmenopausal clinic
      completed the study. All participants were nonsmokers whose pulmonary function
      tests were normal. HCT was performed twice before the inception of ERT, and a
      third time 4-6 weeks after ERT was begun. None of the 36 women demonstrated a 20%
      decrease in FEV1 values (PC20) after inhaling histamine at a concentration of 8
      mg/ml, either before or during ERT. The maximal decrease in FEV1 values in
      response to the maximum concentration of histamine was significantly lower during
      ERT compared to the pretreatment period. The average maximal decrease in FEV1
      during ERT was 2.63 +/- 2.72% (mean +/- DS) compared to 5.21 +/- 4.47% and 6.57
      +/- 5.28% on the 2 tests prior to therapy (p < 0.0002). We conclude that ERT has
      an inhibitory effect on the bronchial reactivity of respiratory smooth muscle.
      There is no cause for concern about increased airway reactivity as an adverse
      effect of this therapy.

PMID- 8578017
TI  - Pathogenetic and clinical significance of fibroblast activation in scleroderma
      lung disease.
AB  - Fibrosing alveolitis (FA) is a major and often fatal complication of systemic
      sclerosis (SSC). The critical role of fibroblasts in the pathogenesis of FA has
      long been recognized. Characterization of fibroblast activation in the lungs may
      improve our understanding and the management of this disease. We analyzed
      bronchoalveolar lavage (BAL) fluid samples from 9 healthy controls and 43
      patients with FA caused by lung involvement form SSC. The chemoattractant
      activity (CAA) of cultured human fibroblasts elicited by native BAL fluid was
      measured in Boyden chambers. In addition, procollagen III peptide was measured in
      BAL fluid as a marker of collagen synthesis. CAA (expressed as percentage of the
      chemoattractant effect of 0.25 ng/ml platelet-derived growth factor; PDGF) was
      elevated in the SSC patients compared with that of the controls (control: 12.6 +/
      4.0%; SSC: 68.8 +/- 15.2%; p < 0.01). A positive correlation was found between
      BAL total cell count and CAA (r = 0.60, p < 0.01). An inverse correlation existed
      between CAA and total lung capacity (r = -0.55, p < 0.05). The patients were
      followed up for 13.3 +/- 1.4 months (mean +/- SEM). Twenty-seven patients
      received immunosuppressive therapy, whereas 16 refused therapy. The patients were
      assigned to two groups according to their CAA being lower or higher than 36% of
      the PDGF response (= mean value of the controls + 2 SD).

PMID- 8578018
TI  - Effect of roxithromycin on peripheral neutrophil adhesion molecules in patients
      with chronic lower respiratory tract disease.
AB  - To evaluate the effects of roxithromycin in patients with chronic lower
      respiratory tract disease including diffuse panbronchiolitis, we studied
      lymphocyte function-associated antigen-1 (LFA-1) and Mac-1, neutrophil adhesion
      molecules, using peripheral neutrophils from healthy volunteers and from patients
      with chronic lower respiratory tract disease. The number of Mac-1 expressed on
      neutrophils of the patients was significantly greater (0.68 +/- 0.16) than in the
      healthy subjects (0.45 +/- 0.14), while the number of LFA-1 expressed on
      neutrophils of the patients was nearly similar to that in the healthy volunteers
      (0.95 +/- 0.10 vs 0.89 +/- 0.11). The neutrophil numbers in bronchoalveolar
      lavage fluid and the number of Mac-1 expressed on peripheral neutrophils
      significantly decreased in all patients who responded clinically to a low dose of
      roxithromycin for a long period of time (56.0 +/- 25.2 vs. 22.7 +/- 19.7%, p <
      0.05 and 0.70 +/- 0.16 vs. 0.59 +/- 0.08, p < 0.05, respectively), whereas
      roxithromycin had no effect on the quantitative expression of LFA-1 (0.96 +/-
      0.14 to 1.00 +/- 0.09, not significant) in all responders.

PMID- 8578019
TI  - Glutathione S transferase Pi is a powerful indicator in chemotherapy of human
      lung squamous-cell carcinoma.
AB  - We immunohistochemically investigated the expression of glutathione S transferase
      pi (GST- pi) and clarified the correlation between GST-pi and the results of
      chemosensitivity testing on the tissue of primary human squamous-cell carcinoma
      of the lung. The expression of GST-pi was evaluated in 105 cases and their level
      of chemosensitivity was estimated by the in vitro succinate dehydrogenase
      inhibition test for cisplatin, Adriamycin, cyclophosphamide, mitomycin C,
      vindesine and fluorouracil. Tumors in which 25% and more of the cells stained for
      GST-pi were classified as having a high GST-pi expression, while those tumors
      demonstrating less than 25% of the cells staining for GST-pi were considered to
      have a low expression GST-pi. The percentage of high GST-pi was 52% (53 of 105)
      while that of low GST-pi was 48% (52 of 105). No significant correlation between
      the expression of GST-pi and clinicopathologic factors was observed, while no
      significant difference in the survival of the two groups was found either. An
      increase in succinate dehydrogenase activity was recognized in the high-GST-pi
      group compared with the low-GST-pi group for each anticancer drug; however, no
      statistical significance was seen except for cisplatin. In the cases with
      adjuvant combination chemotherapy using cisplatin after a complete resection, all
      cases demonstrating a relapse were associated with a high GST-pi. These findings
      thus indicate that an overexpression of GST-pi is related to the resistance to
      cisplatin in human lung squamous-cell carcinoma. It is therefore important to
      select carefully the optimal anticancer drug for high-GST-pi cases.

PMID- 8578020
TI  - Reversible bronchial hyperresponsiveness induced by OK-T3/IL-2 administration in
      a patient with multiple myeloma.
AB  - Severe bronchial hyperresponsiveness to methacholine developed after intravenous
      therapy with OK-T3 and IL-2 in a patient with multiple myeloma, in whom no
      factors known to be associated with bronchial hyperresponsiveness were present. A
      substantial increase and activation of peripheral T-lymphocytes was observed
      after immunotherapy. Bronchial responsiveness and lymphocyte subsets both
      returned to normal baseline values 2 months after the patient was shifted to
      subcutaneous low dose administration of IL-2. The strict association between
      peripheral T-lymphocytes activation and the development of bronchial
      hyperresponsiveness suggests a causal relationship.

PMID- 8578021
TI  - Poorly differentiated non-small cell carcinoma of the lung in acquired
      immunodeficiency syndrome.
AB  - Case of a 33-year-old female with AIDS who presented with fevers, chills, lower
      back pain and a large right hilar mass. Biopsy of the right paratracheal nodes
      revealed poorly differentiated non-small cell carcinoma with extensive necrosis.
      In patients infected with HIV the incidence of primary lung carcinoma is unknown.
      Despite these uncertainties, primary lung carcinoma must be considered in the
      differential diagnosis of young HIV-infected individuals presenting with
      intrathoracic radiographic abnormalities.

PMID- 8578022
TI  - Recurrent mediastinal bronchogenic cyst.
AB  - A patient with a new mediastinal mass 25 years after resection of a mediastinal
      bronchogenic cyst is presented. Computed tomography and subsequent thoracotomy
      revealed a recurrent bronchogenic cyst. This case illustrates that incompletely
      resected mediastinal bronchogenic cysts may recur many years later.

PMID- 8578023
TI  - Work-up of lymphadenopathy in children.
AB  - Lymphadenopathy occurs frequently in childhood caused by both reactive and
      neoplastic origins. Correlation of clinical findings, historical information, and
      patient symptoms may provide important insights into the cause of
      lymphadenopathy. When malignancy is suspected or if a child does not respond to
      antibiotic therapy, nodal biopsy or cytological examination may be undertaken to
      establish a diagnosis. Proper handling of pathologic materials will enhance the
      pathologist's ability to make an accurate diagnosis and may allow for important
      ancillary testing to be performed.

PMID- 8578024
TI  - Benign lymphadenopathies in children and adolescents.
AB  - This article provides and overview of the benign causes of lymphadenopathy (LA)
      in the pediatric population. Because of the topics' broad nature, this review is
      a selective one and primarily focuses on benign conditions of lymph nodes that
      may be confused with malignant disorders or have been described or better defined
      in recent years. Specifically, these will include infectious LA caused by Epstein
      Barr virus (EBV), human immunodeficiency virus (HIV), and cat scratch disease
      (CSD), LA associated with vaccination, drug-associated LA, progressive
      transformation of germinal centers (PTGC), LA associated with autoimmune
      disorders, histiocytic proliferations involving lymph nodes, and Kawasaki
      disease.

PMID- 8578025
TI  - Classification of non-Hodgkin's lymphomas in children.
AB  - Pediatric non-Hodgkin's lymphomas (NHLs) comprise an important subset of
      childhood malignancies with characteristic clinical, histologic, cytogenetic, and
      immunologic findings. Lymphoblastic lymphoma, small noncleaved cell lymphoma, and
      large cell lymphomas comprise the vast majority of childhood NHLs. Proper
      distinction of these subsets of NHL has important therapeutic and prognostic
      implications for the patient.

PMID- 8578026
TI  - Peripheral T-cell lymphomas in children.
AB  - Approximately 20% of childhood non-Hodgkin's lymphomas (HNLs) are of peripheral T
      cell type. These lymphomas form a heterogeneous group of neoplasms with different
      clinical features and responses to therapy. By far the most common among these
      lymphomas is the recently described Ki-1+ large cell lymphoma (LCL), but other
      types of peripheral T-cell lymphomas, which may rarely occur in children, include
      plemorphic T-cell lymphomas resembling adult T-cell leukemia/lymphoma (ATLL),
      angiocentric immunoproliferative lesions (AIL), angioimmunoblastic
      lymphadenopathy-like T-cell lymphoma, and cutaneous T-cell lymphoma (CTCL).

PMID- 8578027
TI  - Acute lymphoblastic leukemia and the lymphoblastic lymphomas of childhood.
AB  - Recent advances in diagnosis, treatment, and tumor biology of the lymphoid
      blastic malignancies have challenged historical concepts and created a need for
      revised classification of these diseases. The authors review this material and
      present a classification relevant to current therapeutic protocols and available
      biological data. Further advances in understanding of these diseases can be
      anticipated, with possible further evolution of classification. The exact
      clinical role of sensitive studies to monitor residual disease during and after
      treatment remains to be established. These diseases may present difficult
      differential diagnostic problems. The importance of accurate diagnosis cannot be
      overemphasized, as highly successful but divergent treatments have evolved for
      these various hematopoietic diseases. Diagnostic problems are usually resolved
      with systematic analysis including careful morphology, cytochemistry, immunologic
      analysis, and addition of EM and other studies in selected circumstances.

PMID- 8578028
TI  - Molecular biology and cytogenetics of non-Hodgkin's lymphoma in children.
AB  - Molecular analysis, combined with cytogenetic studies of proto-oncogenes and
      tumor suppressor genes, has provided insight into the pathogenesis of non
      Hodgkin's lymphoma. Characterization of these malignancies at the molecular level
      will aid in developing more sensitive detection methods for earlier and more
      accurate diagnosis. Thus, genetic rearrangements provide highly specific
      molecular markers for monitoring malignant cells. Additionally, a more detailed
      understanding of the precise, molecular steps leading to malignant transformation
      will facilitate the development of more specific and, perhaps, less toxic
      therapies.

PMID- 8578029
TI  - Symptom experience.
AB  - OBJECTIVE: To provide an overview of symptom experience, symptom occurrence, and
      symptom distress. DATA SOURCES: Published articles relating to the symptom
      experience, symptom occurrence, and symptom distress of patients with cancer.
      CONCLUSIONS: Symptom experience must include both the occurrence and distress
      associated with the symptom. To adequately assess symptom experience, obtaining
      information from patient about the occurrence and distress of the symptom
      experience is essential. IMPLICATIONS FOR NURSING PRACTICE: Nurses and other
      health care professionals can perform an essential role in the identification and
      management of symptom experience, thereby improving patient quality of life.

PMID- 8578030
TI  - The symptom experience of alopecia.
AB  - OBJECTIVES: To examine the physiology and pathophysiology of loss of hair, the
      impact of alopecia on the patient, nursing and self-care interventions, and
      available resources. DATA SOURCES: Published articles pertaining to alopecia and
      personal experiences of coping with alopecia. CONCLUSIONS: Hair loss often is the
      most traumatic side effect for cancer patients. It causes depression, loss of
      self-confidence, and humiliation in men and women of all ages. Too few studies
      exist to make a definitive recommendation for scalp hypothermia and the use of
      scalp tourniquets. The major controversy and issue to consider with these hair
      preservation techniques is scalp metastases. Further studies are needed to
      identify the impact of alopecia on patient self-image and quality of life.
      IMPLICATIONS FOR NURSING PRACTICE: Nursing interventions should be directed
      toward helping the patient and family adapt to and cope with alopecia. Patient
      education, identification of available resources, and supportive listening are
      therapeutic interventions.

PMID- 8578031
TI  - Management of cutaneous symptoms.
AB  - OBJECTIVE: To provide a review of the problems of malignant skin lesions, skin
      changes associated with cancer therapy, and required nursing care. DATA SOURCES:
      Published articles and book chapters that pertain to skin, malignant skin
      lesions, cutaneous toxicity from cancer therapy, pressure ulcers, and nursing
      care. CONCLUSIONS: Cutaneous symptoms as a result of the disease process or its
      treatment (chemotherapy, cytokines, radiation) interfere with optimal functioning
      and quality of life. The management and nursing care of malignant skin lesions,
      hyperpigmentation, changes in sensation, hypersensitivity reactions, acral
      erythema, erythema, desquamation, and pressure ulcers provide major treatment
      challenges for the oncology nurse. IMPLICATIONS FOR NURSING PRACTICE: Skilled
      assessment, prevention, intervention, and evaluation of skin problems can reduce
      the difficulties patients and family members encounter with cutaneous symptoms
      and promote self-care and optimal functioning.

PMID- 8578032
TI  - The symptom experience of mucositis, stomatitis, and xerostomia.
AB  - OBJECTIVE: To provide an overview of mucositis, stomatitis, and xerostomia, the
      symptom experience, risk factors, current therapies, nursing interventions, and
      implications for practice, research, and education. DATA SOURCES: Published
      articles pertaining to mucositis, stomatitis, and xerostomia. CONCLUSIONS:
      Complete and consistent assessment of the oral cavity are needed. Frequent and
      meticulous oral care remains an important factor in preventing the development of
      or reducing the severity of oral mucositis, stomatitis, and xerostomia.
      Additional research of these symptoms is needed. IMPLICATIONS FOR NURSING
      PRACTICE: Oncology nurses can perform an essential role in promoting oral hygiene
      and optimal status of the oral cavity during cancer and its treatment.

PMID- 8578033
TI  - Nausea, vomiting, and retching: the management of the symptom experience.
AB  - OBJECTIVES: To examine the physiology of nausea, vomiting, and retching (NVR);
      the impact of NVR on the patient: current measures to control NVR; and selfcare
      interventions. DATA SOURCES: Research studies, abstracts, and review articles
      relating to NVR associated with cancer treatment as well as pharmacological and
      nonpharmacological interventions. CONCLUSIONS: Management of the individual
      symptoms of NVR require expert, ongoing assessment of the patient's symptom
      experience that extends beyond the clinic or hospital visit. Although a number of
      pharmacological antiemetic agents are currently available and additional
      antiemetic drugs are in phase II or II trials, nonpharmacological interventions
      are essential to achieve effective management. IMPLICATIONS FOR NURSING PRACTICE:
      Continual assessment of the individual's symptom experience is imperative.
      Effective management of the symptom experience depends on the oncology nurses's
      ability to implement current knowledge of antiemetic, and other drugs; non
      pharmacological interventions; and cost-effective and clinically useful patient
      outcomes.

PMID- 8578034
TI  - Anorexia, cachexia, and dysphagia: the symptom experience.
AB  - OBJECTIVES: To review the symptoms of anorexia, cachexia, and dysphagia and to
      provide information on nutritional assessment and interventions. DATA SOURCES:
      Published studies of anorexia, cachexia, and dysphagia, research abstracts, and
      review articles. CONCLUSIONS: Anorexia, cachexia, and dysphagia can cause severe
      alterations in nutrition in cancer patients that may lead to irreversible
      nutritional compromise and death. Nursing research must focus on symptom
      management of these three symptoms, the needs of the patient and family, and the
      impact of dysphagia on quality of life. IMPLICATIONS FOR NURSING PRACTICE:
      Assessment, objective evaluation, pharmacological interventions, and nutritional
      counseling are important interventions for patients with anorexia and cachexia.
      Swallowing therapy, food intake adjustments, oral hygiene, and supportive care
      are important measures needed by the patient with dysphagia.

PMID- 8578035
TI  - Fatigue and weakness in cancer patients: the symptoms experience.
AB  - OBJECTIVES: To distinguish between fatigue and weakness and review symptom
      management for both and to suggest directions for research and practice. DATA
      SOURCES: Articles and book chapters pertaining to fatigue and weakness.
      CONCLUSIONS: Fatigue and weakness are important but long-neglected symptoms, and
      comparatively little effort has been invested in developing techniques to
      mitigate these symptoms. Research is needed to differentiate between these
      concepts, to determine the relation between fatigue and weakness, to delineate
      their causes, and to develop interventions aimed at the prevention and treatment
      of these symptoms. IMPLICATIONS FOR NURSING PRACTICE: Early assessment of risk
      factors, mobility and sensory problems, and usual level of activity will help
      identify those patients who may benefit from nursing interventions or referrals
      for occupational or physical therapy. It is important to repeatedly evaluate
      these symptoms in relation to treatment, situational changes, interventions used
      to manage other symptoms, and tumor progression. Developing clinical guidelines
      and intervention strategies will contribute greatly to the functional
      independence and the quality of life of patients.

PMID- 8578036
TI  - Symptom management: loss of concentration.
AB  - OBJECTIVE: To review the loss of the ability to concentrate in individuals with
      cancer, the risk factors, and nursing approaches to support and improve
      attentional functioning. DATA SOURCES: Published articles and books pertaining to
      concentration, central nervous system toxicity, attentional fatigue, and
      cognitive dysfunction. CONCLUSIONS: Multiple factors related to cancer, its
      treatment, and the demands of a life-threatening illness increase the risk for
      loss of concentration and attentional fatigue. IMPLICATIONS FOR NURSING PRACTICE:
      Nurses can assess potential loss of concentration by observation and objective
      and subjective measures. Attention can be conserved by reducing environmental
      demands and applying attention-restoring strategies.

PMID- 8578037
TI  - Constipation and diarrhea: the neglected symptoms.
AB  - OBJECTIVE: To review the symptom experience of constipation and diarrhea related
      to cancer and its treatment. DATA SOURCES: Published articles and book chapters
      relating to constipation and diarrhea in patients with cancer. CONCLUSIONS:
      Constipation and diarrhea often represent a major concern and source of
      discomfort for the cancer patients. Research is needed to establish prevention
      and treatment protocols for patients at risk for constipation or diarrhea.
      IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses are in an excellent position
      to recognize individuals who are at high risk for constipation and diarrhea.
      Preventive strategies and treatment protocols are of utmost importance.

PMID- 8578039
TI  - Paradigms and critical communication.

PMID- 8578038
TI  - Patients education: self-care guides.

PMID- 8578040
TI  - Relation between gait speed, knee muscle torque and motor scores in post-stroke
      patients.
AB  - A study was undertaken to investigate the relation between gait speed, motor
      function and isokinetic knee muscle torque in stroke victims. Two different gait
      speeds, freely chosen speed and fastest speed, were measured on a 10-m long
      walkway in 34 stroke victims (median age 71 years) three months after the stroke.
      At the same time different motor functions were assessed, and isokinetic knee
      muscle torque was measured. One year after the stroke 24 of the subjects were
      again investigated. The two gait speeds measured were both slower than those in
      normal healthy subjects of the same age. The motor assessment revealed that the
      group of stroke patients had light to moderately severe stroke symptoms. The
      isokinetic muscle torque was significantly lower in the paretic than in the non
      paretic legs. The non-paretic legs were also weaker than the legs of healthy
      subjects. No significant changes in any of the measured variables were found
      between the three months' assessment and the one year post-stroke assessment.
      There were some significant correlations between gait speed and motor scores and
      between gait speed and muscle torque, but usually of moderate strength. Multiple
      regression analysis with gait speed as dependent variable and combined isokinetic
      muscle torque and three different motor scores as independent variables gave
      higher R values.

PMID- 8578041
TI  - Community nursing in Finland: the division of fields of activity and patterns of
      care--comprehensive or specialized care?
AB  - The aim of this study was, first, to describe the changes taking place in the
      division of fields of activity in Finnish community nursing during a national
      project on primary health care; second, to describe and analyze patterns of care
      by categorizing different points of view in nurses' personal experiences. Data on
      the division of fields of activity in all project areas were collected in a
      survey and in annual registrations of public health nurses' tasks (n = 87-113).
      Care patterns were discerned in focused interviews with public health nurses (n =
      18). Three types of division of fields of activity were identified: the
      comprehensive, semi-comprehensive and specialized model. The comprehensive and
      semi-comprehensive models became more common during the project and the
      specialized one less common. Patterns of care were classified into four main
      categories: structural, individualistic, family-centred and community-centred.
      The division of fields of activity was not always compatible with the care
      patterns. The study identified several issues that should be considered in the
      definition and implementation of comprehensive and specialized care.

PMID- 8578042
TI  - Implementing coordination of care--task performance and problems encountered.
AB  - In recent years the effects of interventions in the field of coordination of care
      have been well reported. However, the implementation of coordination of care is
      hardly addressed. This article focuses on the implementation of coordination of
      care for the elderly in three community settings in The Netherlands. A group of
      38 professional and non-professional care-givers functioned as coordinators
      during a period of one year. Open interviews with coordinators, minutes from
      group meetings and forms and logbooks were used as sources of data. Major
      problems during implementation involved conflicting roles, preserving the
      client's privacy, lack of recognition and the perception that coordination was
      not always necessary. Coordinators had no difficulty in making a care inventory
      and in organizing care. On the other hand, introducing oneself as a coordinator,
      and planning and evaluating are tasks that need more attention in future
      interventions.

PMID- 8578043
TI  - The oldest old and personal activities of daily living.
AB  - The aim of this study was to evaluate the actual function of the personal
      activities of daily living in old people living in nursing homes and in the
      community. Another purpose was to evaluate and document the nursing load. The
      assessments were made over a four-week period. Two groups of individuals, aged 80
      years or older, were compared with respect to ability to perform activities of
      daily living. The first group comprised old people who had been resident in
      nursing homes for at least six months, while those in the other group lived alone
      in the community and received some kind of assistance from the home service
      providers. The subjects in the latter group were less disabled than those
      residing in nursing homes. Age group comparisons among nursing-home residents
      showed no significant differences in the capacity of residents to function in
      activities of daily living, nor in the case of those living in the community. The
      nursing staff in the nursing-home setting had a heavier work-load than those
      working in the community concerning performance of personal activities of daily
      living. Caring for old people in institutions as well as in the community creates
      substantial challenges for the care personnel.

PMID- 8578044
TI  - Activity--from action to activity.
AB  - In this article, existing terminology concerning occupational performance is
      reviewed. The authors conclude that the occupational therapy terminology
      available is insufficient to describe levels of complexity in the performance of
      an activity. Concepts are suggested to describe the different aspects of an
      activity, namely operations, single actions, generated actions, action sequences,
      and simultaneous actions. The suggested concepts are not intended to replace, but
      to supplement existing terminology.

PMID- 8578045
TI  - The dialectic in becoming a mother: experiencing a postpartum phenomenon.
AB  - In this study of the phenomenon of the postpartum period grounded theory
      methodology was used to investigate the experiences of first-time mothers during
      the first three months following their deliveries. The sample consisted of 12
      primipara women and 3 multipara women. The data were generated by using
      unstructured interviews and field notes. Each woman was interviewed twice, the
      first time between 2 and 3 weeks postpartum, and the second time between 10 and
      12 weeks postpartum. The final data for analysis consisted of: data generated
      through interviews, field notes, and the narratives of four mothers found in the
      non-fiction literature. Constant comparative analysis resulted in the generation
      of four categories and corresponding subcategories. These were: (1) Giving of
      Self; (2) Redefining Self; (3) Redefining Relationships; and (4) Redefining
      Professional Goals. The categories were not mutually exclusive. All the
      categories converged to provide support for the core variable 'Dialectic in
      Becoming a Mother'. The dialectic perspective demonstrated that, in becoming
      mothers, the women experienced transition, contradictions, tensions and
      transformations. A theoretical model was developed to show relationships among
      these major concepts. The findings of this study will be useful in effecting
      change in the provision of care to postpartum women and their families.

PMID- 8578046
TI  - The stories of physicians, registered nurses and enrolled nurses about ethically
      difficult care episodes in surgical care.
AB  - Twenty physicians, 19 registered nurses (RN), and 20 enrolled nurses (EN) working
      in surgical care in Sweden narrated their experiences of being in ethically
      difficult care situations. All three professional groups disclosed a strong wish
      to help patients. The narrations of the physicians and the ENs indicated that
      they were very much involved in their patients, while most of the RNs' stories
      were narrated from a distanced onlooker's perspective and disclosed a lot of
      moral outrage, mainly directed towards physicians. The physicians were the only
      group that emphasized the importance of acting in accordance with science and
      proven experience. Like RNs they emphasized the importance and difficulty of
      telling the truth to the patients and their families and being open to one's own
      and others' harsh experiences. RNs and ENs emphasized the patient's right to a
      death with dignity and the difficulties connected with being with dying patients,
      and they also described feelings of powerlessness and neglect of patients related
      to a heavy work load. ENs narrated difficulties related to providing patients
      with individualized but fair care.

PMID- 8578047
TI  - [Cerebral resuscitation: pathophysiological limitations and therapeutic
      possibilities].

PMID- 8578048
TI  - [Diagnosis and therapy strategy in myelodysplastic syndromes].
AB  - Myelodysplastic syndromes (MDS) are diagnosed with increasing frequency in recent
      years. Their crude annual incidence (ca. 4/100,000), is now about twice that of
      acute myeloid leukemias (AML). In over 70-year-old patients (age-related
      incidence more than 20/100,000), MDS rival CLL as the most common hematological
      neoplasias. Diagnosis of MDS is based on cytological and histological examination
      of bone marrow specimens, which may show various dysplastic features of
      hematopoietic precursors and an increased percentage of blast cells. In difficult
      cases the diagnosis of MDS is supported if cytogenetic investigation reveals an
      abnormal karyotype. Most patients with MDS (60 bis 80%) die from their bone
      marrow disorder, with infections, hemorrhages and leukemic transformation being
      the most frequent causes of death. Treatment must take into account the age and
      general condition of the individual patient as well as the natural course of his
      MDS. The comparatively favourable prognosis of patients with early-stage MDS
      should not be jeopardized by therapies carrying a high risk of treatment-related
      death. Therefore, treatment is often confined to supportive measures (blood
      transfusions, antibiotics). Patients with increased percentage of blasts,
      however, have such a poor prognosis that more aggressive approaches including
      intensive chemotherapy appear justified. Only very few patients can be treated
      with allogeneic bone marrow transplantation, which offers a chance for cure.

PMID- 8578049
TI  - [Can past developments foresee the grand picture of the 21st health care system:
      reversal of trends and stability?].
AB  - Social and economic forecasting in the health sector in France is particularly
      uncertain since most indicators have reversed their trends: transfers among
      health care structures (ambulatory care/outpatient care), prices, financing. The
      growth rate of global expense is diminishing and seems to be tending towards an
      asymptote of unknown level. The higher increase of health care among the elderly
      indicates a better correspondence between health care and morbidity, however,
      economic and social disparities, while they decreased from 1960 to 1980, have
      grown since. The improvement of health (life expectancy, invalidity, disability)
      is accompanied by an increase in the amount of disease. Finally, although the
      freedom of policy-makers is limited, their firmly stated will to modify the rules
      increases the uncertainty of the future of health care.

PMID- 8578050
TI  - [A patient with a transplanted kidney with respiratory insufficiency following
      treated Legionella pneumonia].

PMID- 8578052
TI  - [Radiological case of the week (3) Pulmonary alveolar phospholipoproteinosis].

PMID- 8578051
TI  - [A clinical-pharmacological case (1). Action of cisapride (Prepulsid) on bladder
      function].
AB  - We report the case of a 75 old man with chronic constipation due to traumatic
      spinal cord injury 25 years ago. Following prostatectomy the patient developed
      retention of urine and urinary incontinence, which improved significantly during
      a therapy with cisapride (3 x 10 mg/day). While the administration of cisapride
      is associated with increased detrusor activity and possibly urinary incontinence
      in neurologically normal persons, patients with urinary retention due to spinal
      cord injury may benefit from a therapy with this indirect parasympathomimetic
      agent.

PMID- 8578053
TI  - [A case from practice (340). Transient regional osteoporosis of the right knee].

PMID- 8578054
TI  - [Future perspectives in epilepsy treatment].
AB  - The primary goal of a causal (= curative) therapy of the epilepsies is the
      correction of the causes of the epilepsy syndrome. Unfortunately, at present,
      this is only possible to a limited extent. Recent advances have been achieved in
      the discovery of the possible causes of resistance to common antiepileptic drugs
      (increased activity of P-glycoprotein drug efflux-pump in the epileptogenic
      focus), in the discovery of the pathophysiology of some epilepsy syndromes as
      autoimmune diseases (Rasmussen encephalitis), as well as in the understanding of
      a few epilepsy forms as a genetically determined aberrations. Much expectation
      for a more accurate biochemical in-vivo characterization of epilepsy syndromes
      presently lies in the noninvasive proton magnetic resonance spectroscopy, with
      the ultimate goal of a more specific pharmacological therapy with antiepileptic
      drugs. Technical advances, which might gain importance for epilepsy therapy in
      the near future, are 'radiosurgery' and probably also gene-therapy, i.e. the
      treatment of focal epilepsies by intracerebral grafting of GABA- and adenosine
      releasing cells developed in transgenic mice.

PMID- 8578055
TI  - [What is your diagnosis? Acute posterior myocardial infarct].

PMID- 8578056
TI  - [Gabapentin--a new add-on antiepileptic drug].

PMID- 8578057
TI  - [Treatment of epilepsy: where are we today?].
AB  - The modern treatment of epilepsy has improved considerably in all three pillars.
      More than a century has passed, however, since Sir Charles Locock introduced the
      bromides in 1857 and Sir Victor Horsely pioneered epilepsy surgery in 1886 (18).
      In drug therapy, the 'classic AED' of the last decades, i.e. phenobarbital
      (Hauptmann, 1912) and phenytoin (Putnam and Merrit, 1938) are being largely
      displaced by valproate (Meunir, 1963) and carbamazepine (Lorge, 1963). Only
      ethosuximide (Zimmermann, 1951) has continued to maintain its position in 3/s
      spikewave-absence epilepsy, in particular in the USA (28, 29). Although it is an
      excellent drug against absences, it has the unpleasant property that it may
      induce GM seizures and should therefore be combined with a so-called 'GM
      protector' (mostly phenobarbital). For this reason ethosuximide has been
      relegated to second place in Europe by valproate. Thus, the decision as to which
      AED should be employed at the outset has been simplified considerably: actually,
      with valproate as the drug of first choice, which displays a very broad spectrum
      of action, we are on the right track for virtually all forms of epilepsy, perhaps
      with the exception of focal epilepsy (11). Especially in the event of focal
      epilepsy of temporal origin we employ carbamazepine as the preparation of first
      choice. In some countries (Denmark), because of the less severe side effects,
      oxcarbazepine is already preferred (Mogens Dam, personal communication).
      Considerable experience and knowledge are still required, however, when
      resistance has developed to traditionally applied classic monotherapy. Here, the
      range of further treatment can also be greatly extended by the availability of
      the 'new AED'. A generally accepted protocol for the replacement of one
      preparation with another first- or second-choice drug and, above all, for the
      'right' combination with third-choice preparations can as yet not be compiled.
      What we need here is the expert epileptologist who has experience with
      'theoretically useful' combinations and has an insight into the interactions
      occurring with such combinations. For several specific epileptic syndromes the
      'Konigsteiner Working Group of German-Speaking Epileptologists' has given clear
      and binding recommendations for AED therapy (e.g. for benign juvenile myoclonic
      epilepsy--Janz syndrome). This working group has also made recommendations for
      the necessary clinical and laboratory controls in AED therapy with potentially
      severe side effects (e.g. valproate therapy in high-risk children), which were
      published and/or are being published and discussed in the 'Epilepsie-Blatter' of
      the German League against Epilepsy (4). Despite all advances in drug therapy, the
      number of epilepsy patients not satisfactorily treatable with drug therapy has
      not been dramatically reduced statistically, so that the other two pillars of
      epilepsy therapy, i.e. epileptic surgery and behavioural therapy, continue to be
      very important.

PMID- 8578058
TI  - [Current role of novel antiepileptics in the treatment of epilepsies].
AB  - Although standard anticonvulsants are effective in achieving complete seizure
      control in the majority of patients, an appreciable proportion (about 20 to 25%)
      is at least in part resistant to conventional pharmacotherapy. Efficacy of
      carbamazepine, phenytoin, phenobarbital and valproate is very similar. Should one
      drug fail because of inadequate efficacy or unacceptable adverse effects, an
      alternative monotherapy should be used. Surgical treatment is a feasible
      therapeutic option for only some of these patients. The development of newer,
      more effective drugs such as vigabatrin, lamotrigine, gabapentin and
      oxcarbazepine would be highly desirable. The search for new antiepileptic agents
      is justified to reduce the proportion of drug-resistant patients. Choice of
      conventional or new drugs should include not only expected efficacy and risk of
      adverse effects, but pharmacokinetic properties and expense. Consequently, no
      general rule is appropriate, and each decision and recommendation for treatment
      should be individualized.

PMID- 8578059
TI  - [Gabapentin (Neurontin): a new possibility in the add-on therapy of partial
      epilepsies].
AB  - Gabapentin is a new antiepileptic drug for add-on therapy in patients above the
      age of 12 years with otherwise refractory partial seizures. Its unknown molecular
      mode of action is probably related to amino-acid-related binding sites in the
      brain. There are no hints to toxicologic effects or damage of the hematopoietic
      system, liver, or kidney in man. With the exception of a rather short elimination
      half life and dose-limited abortion, the pharmacokinetic data are very
      favourable. Due to lack of protein binding and metabolization, there are no major
      interactions with antiepileptic or other drugs. Efficacy has been demonstrated in
      three multicenter, placebo controlled trials involving a total of 705 patients.
      Secondarily generalized seizures seem to be the most likely to respond to 900 to
      1800 mg/day, followed by complex partial and simple partial seizures. Tolerance
      is good, and serious side effects have not been observed up to now.

PMID- 8578060
TI  - [Clinical studies on gabapentin in Switzerland].
AB  - Gabapentin is a new antiepileptic for the combination therapy of partial
      seizures. It was introduced in January 1995 in Switzerland. This article
      describes briefly the ongoing clinical studies in Switzerland; meanwhile, these
      multicenter studies are conducted in different countries. An open study will
      evaluate the number of seizure-free patients under therapy with different dosages
      of gabapentin as add-on therapy. The efficacy and tolerance of gabapentin will be
      compared with carbamazepine as monotherapy. The last study examines the efficacy
      of gabapentin for the treatment of partial seizures in pediatric population.

PMID- 8578061
TI  - [Recommendations on clinical epilepsy treatment using gabapentin].

PMID- 8578062
TI  - [Perceptions and Agnosia. Proceedings of an international meeting of the French
      Society of Neurology. Paris, 9-10 June 1994].

PMID- 8578063
TI  - [Cognitive processes in perception: perceptive knowledge].
AB  - In an information processing approach, this paper attempt to show how different
      levels of processing visual information can be organized Sensory processing makes
      local coding of some dimensions. Then comme a step of structuration consisting in
      "putting together" these locally coded dimensions. These informations have
      finally to be interpreted on the basis of cognitive representations. Several
      examples are presented illustrating how ambiguities can appear between sensory
      information and various cognitive interpretations.

PMID- 8578064
TI  - [Perception and memory: illustration of an approach of the study of visual
      mechanisms in cognitive neuroscience].

PMID- 8578065
TI  - [Anatomo-physiological bases of residual vision following lesion to the primary
      visual area. Contribution to electrophysiological approach in monkeys].
AB  - This paper presents several studies aimed at determining which brain structures
      are responsible for residual vision observed after a lesion of the primary visual
      area. A description of this phenomenon in man and in monkeys is first provided.
      Recent results are then described that indicate that residual vision is mediated
      by the dorso-parietal pathway of visual information transfer. The ventro
      inferotemporal pathway is inactivated by a block or a lesion of the primary
      visual cortex.

PMID- 8578066
TI  - [Perception in space. Visual aspects of space perception].
AB  - The ability to apprehend and appropriate space is based on a series of perceptive
      and cognitive processes, in which vision plays a leading part. Preliminary,
      elementary operations first allow a subject to achieve the elaboration of a
      visually structured percept. Both experiences on healthy subjects, and
      pathological data have provided evidence for a right hemisphere superiority in
      tasks such as localization of stimuli and discrimination of line orientation.
      Depth perception rests both on indirect cues (e.g. relative size of objects,
      perspective and movement parallax) and on two types of specific stereoscopic
      processes: the so-called local and global stereoscopies, which depend
      respectively on the integrity of visual cortices and of inferior occipito
      temporal areas (with a right-hemisphere dominance). Movement perception is
      integrated at the level of area V5, at the lateral occipito-temporal junction on
      both sides. The accuracy of reaching movements and displacements within space
      require the elaboration of a system of coordinates in which the position of the
      egocentric reference will then be taken into account. This is achieved by
      successive coding of eye and head position relative to the body axis, and by
      building the body reference from proprioceptive and vestibular afferences to the
      parietal cortex. Finally, attention must be both diffusely scattered throughout
      the whole space and voluntarily allocated as needed on a given object.
      Simultanagnosia and unilateral spatial neglect (USN) are examples of disruption
      of these attentional processes. Simultanagnosia illustrates the loss of the
      ability to shift attention from one point to another, but both shrinking of the
      attentional field and poorly sustained fixation are also possible mechanisms of
      this syndrome. USN probably has several components. Unilateral brain damage
      causes interhemispheric attentional imbalance that explains the attentional
      preference for the ipsilesional side of space. The predominance of neglect
      following right-sided lesions might be the consequence of hemispheric
      specialization regarding directed attention, with the left hemisphere
      preferentially allocating attention to objects and the right one being able to
      attend to the whole space. The anatomical basis of such a functional
      differentiation is still unclear.

PMID- 8578067
TI  - [Imagery and its neurological substrate].
AB  - What is the nature and the neural substrate of mental representation? This paper
      reviews findings from experimental psychology demonstrating that visual imagery
      and perception have similar characteristics. These results suggest that visual
      imagery and visual perception rely on the same neural substrate. Brain imaging
      studies as well as clinical observations of neurological patients support this
      hypothesis. Visual imagery involves visual cortical areas. However, selective
      visual impairments following damage to the cortical visual system may produce
      some dissociation between imagery and perception. Similar observations concerning
      motor imagery are now established in both normals and in neurological patients.
      Evidence that motor imagery and motor control share some modality specific neural
      representations are clearly supported by tomographic measurements of cerebral
      blood flow.

PMID- 8578068
TI  - [Reading numbers in pure alexia: effects of the task and hemispheric
      specialization].
AB  - Selective conservation of the ability to read Arabic numbers in patients unable
      to read words or even letters is a classical characteristic of pure alexia
      described by Dejerine (1982). We report our work on the capacity of two patients
      with pure typical alexia to process numbers. Our main finding was that these
      patients could count pairs of Arabic numbers correctly when the reading task was
      simple (example 2 4-->"two four") or when the task involved comparing sizes
      (example 2 4-->"four is bigger than two"). Inversely, these patients often made
      mistakes when asked to perform arithmetic operations (example 2 4-->"two plus
      four equals six"). Using these two numbers, there was a similar dissociation
      between excellent performance on comparison tests and severe deficiency in
      reading out loud. We interpret these findings with the hypothesis that both of
      the hemispheres can identify Arabic numbers, but that the visual systems on the
      right and left play a different role during different tasks. In pure alexia, a
      lesion in the left identification system leads to selective deficiency in
      linguistic tasks such as reading numbers out loud, recognizing numbers with
      several figures or mental arithmetic. The right identification system in intact
      and is sufficient for comparison or reading isolated Arabic numbers.

PMID- 8578069
TI  - Anatomy of the auditory cortex.
AB  - Cortical auditory areas located in the superior temporal region (STR) in monkey
      and human. The primary auditory area (AI) occupies the cortex of the
      supratemporal plane (STP) and is surrounded by auditory association areas in
      circular sulcus and superior temporal gyrus (STG). Architectonic studies have
      parcellated auditory areas into a number of subregions. Beginning from the
      temporal polar proisocortex up to the parietal cortex, these areas shows
      progressive laminar differentiation, and are arranged into three parallel lines.
      The most medial line occupies the cortex of the circular sulcus. The regions of
      this line maintains limbic features and is termed as root line. Another line is
      located in STG. The regions of this line show progressive emphasis in the third
      and fourth layer neurons and is termed as belt line. Interposed between root and
      belt line is a core line located in STP. In this line there is greater
      accumulation of fourth layer neurons. Recent physiological studies have outlined
      several auditory representations surrounding AI. These auditory representations
      correspond to above mentioned architectonic subregions of STR. The subregions
      within each line have bidirectional connectional laminar specificity. The
      feedforward connections originate from the supragranular layer III and terminate
      in the around layer IV of the rostrally adjacent region. Feedback projections in
      contrast stem from the infragranular layers and terminate in layer I. The long
      association connections of auditory areas are with the prefrontal cortex (PFC),
      the multimodal areas and the limbic regions, and are derived from belt and root
      line areas of STR. These projections follow the rostro-caudal architectonic
      differentiation of STR. Thus the rostral STG areas are mainly connected with
      orbital and medial PFC areas whereas the caudal STG areas are connected with
      caudal PFC. The intermediate STG areas are preferentially related to the lateral
      PFC regions. It seems that STG-PFC connections are between the areas with similar
      level of architectonic differentiation. The thalamic connections of the
      subregions of STR also follow the architectonic organizations. The core line
      areas are preferentially related to ventral nucleus (MGv) of medial geniculate
      nucleus (MGN) whereas the root and belt line areas are connected respectively to
      magnocellular (MGmc) and dorsal (MGd) subdivisions of MGN. The root and belt
      areas share some connections and are also related to pulvinar, suprageniculate,
      dorsomedial and intralaminar nuclei. It seems therefore that progressive laminar
      and tripartrate organization of auditory regions of STR is reflected in
      intrinsic, association and thalamic connections. The feedforward connections may
      be engaged in analysis of external environmental cues whereas feedback
      connections may have a role in matching learned or stored information with
      incoming auditory signals. The preferential core line connectivity with MGv may
      be involved in spectral analysis of sound whereas the connections of the belt and
      root areas with MGmc, MGd, and pulvinar may have role in sound pattern
      recognition, auditory memory, the localization of sound in space as well as
      matching auditory information with other modalities.

PMID- 8578070
TI  - [Cortical mechanisms of auditive perception in man: contribution of cerebral
      potentials and evoked magnetic fields by auditive stimulations].
AB  - The goal of this study is to determine and localize the generators of different
      components of middle latency auditory evoked potentials (MLAEPs) through
      intracerebral recordings in auditory cortex in Human (Heschl's gyrus and Planum
      Temporale). The intracerebral data show that the generators of components at 30,
      50, 60 and 75 msec latency are distributed medio-laterally along the Heschl's
      gyrus. The 30 msec component is generated in the dorso-postero-medial part of the
      Heschl's gyrus (primary area) and the 50 msec component is generated laterally in
      the primary area. The generators of the later components (60-75 msec) are
      localized in the lateral part of the Heschl's gyrus that are the secondary areas.
      The comparison with the generators of the components of the magnetic auditory
      evoked field and the tonotopic organization of the auditory cortex are discussed.

PMID- 8578071
TI  - [Neuropsychology of musical identification].
AB  - Several neuropsychological observations have suggested that disturbances of the
      process involved in identifying music is related to lesions of the dominant
      cerebral hemisphere. The studies have been confirmed by different data from
      experimental psychology and functional brain imaging techniques. Based on these
      inference sources we propose different hypotheses to describe the cognitive
      processes involved in identifying music.

PMID- 8578072
TI  - [Study of functional neuro-anatomy of perception using positron emission
      tomography].
AB  - The investigation by means of functional neuroimaging techniques, notably
      positron emission tomography, of the neural networks involved in perceptual
      processes is presently carried out according to two different though
      complementary approaches. In one of them, the relationships between impairments
      in perceptual processes and alterations in resting brain metabolism are studied
      in brain-damaged subjects, according to the classic paradigm of neuropsychology,
      but here the metabolic alterations reflect the functional disruption of neural
      networks directly or indirectly affected by the focal brain lesion. In the other
      approach, one records the changes in local synaptic activity in response to a
      given stimulation or task, as compared to a reference condition; thus far this
      second approach has been mainly applied to the normal human subject. Though
      different, both approaches highlight the neural networks involved in a given
      perceptual or cognitive task, which appear as a set of brain areas more extensive
      than that revealed by classic neuropsychology as necessary to perform the task.
      PET activation studies in the healthy subject have allowed to investigate, within
      each domain of perception, the successive "bottom-up" steps of information
      processing, from the most elementary ones carried out passively, to the most
      complex ones involving e.g., the semantic representations. The attentional
      aspects of perception have also been extensively investigated, notably selective
      "top-down" attention (which modulates the response of those brain areas that
      process the given perceptual attribute), sustained vigilance (which activates a
      parieto-prefrontal network in the non-dominant hemisphere), and mental imagery
      (which activates in a "top-down" fashion the entire perceptual network, including
      the primary cortices). The wide-scale application of this approach to brain
      damaged subjects will seemingly soon provide important clues regarding the neural
      mechanisms of impaired perception and recovery therefrom.

PMID- 8578073
TI  - [Tactile agnosia and dysfunction of the primary somatosensory area. Data of the
      study by somatosensory evoked potentials in patients with deficits of tactile
      object recognition].
AB  - The question as to whether a failure of recognition unrelated to impaired sensory
      processing or to disorder of naming can occur in the somato-sensory modality has
      been eagerly debated in the french neurology. Taking as an argument the fact that
      he had never observed a tactile agnosia in the absence of subtle sensory deficits
      Dejerine denied the localizing value of tactile agnosia (or asterognosis).
      Conversely Delay, 20 years later, identified tactile performances such as
      discrimination of texture and shapes, which he considered as a specific
      neocortical function, that were lost in parietal syndromes with astereognosis and
      preserved elementary sensations. He also coined the term "tactile asymbolia" to
      qualify the patients with astereognosis in whom these performances are preserved.
      When referring to the definition of agnosias only "tactile asymbolia" should be
      considered as a "true" tactile agnosia. The recording of early somatosensory
      evoked potentials (SEPs) now offers the possibility of assessing non invasively
      the function of the primary somatosensory cortex (in particular area 3b). We have
      recorded SEPs to median nerve or finger stimulation in 309 subjects with a focal
      hemispheric lesion presenting with a somatosensory deficit of any type. We could
      confirm that asterognosis referable to impaired discrimination of textures and/or
      shapes in the absence of impaired elementary sensation is quite rare since it was
      observed in only 12 of our patients (3.9%). Moreover early cortical SEPs
      reflecting the activity of the primary somatosensory area (N20 or/and P27) were
      clearly abnormal in all of them. A single patient of this group of 12 could be
      considered as a case of tactile asymbolia but his early cortical SEPs were
      abnormal. The only condition combining a failure of tactile recognition of
      objects with normal early SEPs is represented by the "tactile anomia" observed in
      callosal dysconnexions. Thus, in our patients unable to identify objects by
      palpation in spite of preserved elementary sensation, we were unable to identify
      a case of pure tactile agnosia. These results are to be confronted with the
      recent observation by Caselli (1991, 1993) that tactile object recognition is
      partially, but selectively, impaired in inferior parietal lesions supposed to
      disconnect the ventrolateral associative somatosensory cortex from its limbic
      targets.

PMID- 8578074
TI  - Editor and authors: common way.

PMID- 8578075
TI  - The use of research results: at which stage are we in Brazil?

PMID- 8578076
TI  - Zinc deficient diet consequences for pregnancy and offsprings of Wistar rats.
AB  - Adult female Wistar rats (90 days old; weight 180 to 220 grams) were submitted to
      different zinc deficient diets (Zn; severe = 2.6 ppm; mild = 9.0 ppm and normal
      diet = 81.6 ppm), during 6 weeks. After this time they were coupled with normal
      male Wistar rats. No differences regarding fecundity and sterility were observed
      between the groups. During pregnancy, part of the animals from severe and mild Zn
      deficient groups received the same diet and the others received normal diet. The
      animals from the group receiving normal diet, were divided into other 3: the
      first received severe, the second mild Zn deficient diet and the third normal
      diet. During the study we observed that animals submitted to a Zn deficient diet
      (acute or chronic) had tendency to lower weight gain, lower weight of the
      offspring, lower serum levels of Zn in maternal and newborn (pool) blood. A
      significant reduction in the number of alive newborns was observed in the group
      of animals submitted to severe Zn deficiency. These data reinforces that Zn is a
      very important trace element overall during pregnancy.

PMID- 8578077
TI  - A study of the pharmacological actions of Dioclea grandiflora Martius ex Bentham.
AB  - Dioclea grandiflora Mart. ex Bent., known as Mucuna or Mucuna of stone, is a
      member of the Leguminosae family, popularly used for its possible effects on the
      Central Nervous System (CNS). Reports mention sedative, tonic, and also
      antiepileptic properties for this plant. In this paper a screening for CNS action
      was done with aqueous extracts of the seeds. This study was carried out using
      some animal models for the study of sedative, hypnotic, anxiolytic,
      anticonvulsive and neuroleptic activity. The results showed that Dioclea
      grandiflora Mart. ex Bent. demonstrates the general profile of a CNS depressant
      drug. However, the extract did not exhibit any of the specific profiles tested.
      Moreover, the results suggest a possible toxicity stemming from the popular or
      folk use of this plant.

PMID- 8578078
TI  - Nucleolar organizer region (NORs) in pseudocarcinomatous hyperplasia and squamous
      cell carcinoma of the oral mucosa.
AB  - Counts of nucleolar regions (NORs) demonstrated by a silver staining technique in
      paraffin sections, have been used to distinguish benign from malignant lesions.
      AgNORs were studied in 24 biopsies from oral cavity (5 cases of normal oral
      mucosa, 5 of pseudocarcinomatous hyperplasia and 14 of squamous cell carcinoma,
      subdivided according to degree of differentiation: 5 grade 1, 5 grade 2 and 4
      grade 3) to find whether they were helpful in distinguishing pseudocarcinomatous
      hyperplasia due to chronic parasitic infections from squamous cell carcinoma. Two
      methods of counting AgNORs were used: (A) a simpler one which counts nucleolar
      clusters (AgNU) and satellite AgNORs and the other (B) counting all individual
      AgNORs, including those within AgNUs. In both methods the lowest mean values were
      observed for grade 3 carcinoma, while the highest belonged to grade 2 carcinoma.
      The simpler method (A) was the most useful because AgNU counts showed significant
      difference when pseudocarcinomatous hyperplasia was compared with grade 1 and 2
      carcinomas, which are the most difficult to discriminate from it. However the
      overlapping of values render the technique of limited use in individual cases.

PMID- 8578079
TI  - Endometrial biopsy with uretral plastic No. 12 sonde.
AB  - The authors demonstrate technique for obtaining endometrial fragments in 25
      patients sent to Gynecological Cancer Preventive Service of the Arnaldo Vieira de
      Carvalho Cancer Institute, during the period of September 1991 through January
      1992, presenting abnormal uterine hemorrhage. Technique consists in vacuum
      aspiration with the support of a No. 12 uretral sonde, provided with one lateral
      opening only. Correlation with curettage was positive in 88% of the patients;
      biopsy with sonde did not result in confirmation in three patients only. No
      complications at all were observed (infection, hemorrhage or uterus perforation).
      Authors understand that this method is in conformity with a correct diagnostic
      performance, being a low cost procedure, almost painless, easy to be done and
      furnishing sufficient material for the histo-pathologic diagnosis, in 88% of the
      cases studied.

PMID- 8578080
TI  - Maintenance treatment of diabetic patients, associating arterial obstructive
      tibio-peroneal disease.
AB  - When a melito-diabetic patient presents trophic infected injury on the limb, it
      is essential an evaluation of the circulatory conditions for therapeutic
      procedures orientation. In some circumstances, although arterial pulsation is
      absent, there is no ischemia of tissues. In these cases, the maintenance
      treatment, with eventual resection of the necrosed and infected tissues may be
      adopted. Evolution of 70 diabetic patients with trophic injuries on extremities
      were submitted to a maintenance treatment. Age of patients varied from 28 to 88
      years, with an average of 56.8. The most occurrence was verified in women, with
      42 cases. Diabetes non-dependent on insulin (type II) was observed in 64 patients
      (91.5%), being the remaining 6 patients of type I. Diabetic retinopathy was
      observed in 14 (20%) of the patients, neuropathy in 22 (31%) and nephropathy in 8
      patients (11.4%). All the patients presented arterial pulsation until the
      popliteal region. They were divided in 2 groups, considering trunk arteries of
      legs: Group I, pervial legs arteries, composed by 48 patients; Group II, occluded
      legs arteries, with 22 patients. In what refers to the anatomic local of the
      injuries, patients were classified in three groups: Group A, formed by 32
      patients (45.7%), presenting injuries in one or two toes only, without affecting
      the metatarsic region; Group B, formed by 16 patients (22.9%), trophic injuries
      affecting the metatarsic region and Group C, formed by 22 patients (31.4%),
      injuries affecting the calcaneous region. Injuries in both of the groups were
      caused by mechanical traumatism. Duration of the injury in the inferior member
      varied from 7 to 48 days, resulting in a 12 days average.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8578081
TI  - Nutritional assessment and surgical risk markers in children submitted to cardiac
      surgery.
AB  - In order to assess the nutritional status of children with heart diseases and to
      evaluate nutritional parameters for predicting postoperative complications, 50
      children undergoing to cardiac surgery and classified in high and low surgical
      risk prospectively evaluated. Assessment parameters included anthropometry and
      plasma proteins albumin, transferrin and prealbumin. The nutritional
      classification according to Waterlow's modified criteria showed a high prevalence
      of malnutrition in the population studied (78%). The measures of arm
      circumference when located below the 5th percentile showed a significant
      association with general postoperative complications in the high risk group (arm
      circumference, p = 0.0019; arm muscle circumference, p = 0.0419). The percentage
      of weight per height, serum albumin and transferrin has not played a prognostic
      role concerning postoperative morbidity. The mean value of prealbumin was
      significantly lower in high risk group patients developing postoperative
      infections (p < 0.01) compared to those who did not. The sensitivity-specificity
      analysis of prealbumin as risk indicator for postoperative infection was 87.5%
      and 59% respectively. The nutritional risk classification seems to be a good way
      to identify the subgroups of children with additional postoperative surgical
      risk. However, more specific and sensitive tests are desirable to provide an
      individual identification of these children.

PMID- 8578082
TI  - Multidisciplinary experience in the selection of patients for tubal
      sterilization.
AB  - Results of the use of a special protocol for evaluation of patients requiring
      tubal ligation is presented after applied by a multidisciplinary group. The
      authors conclude that the use of defined parameters of age, parity, marital union
      duration, number of children alive and the presence of maternal clinical
      pathology are useful to identify patients with smaller chances of regret after
      surgery.

PMID- 8578083
TI  - Gallstone ileus resulting in strong intestinal obstruction.
AB  - Mechanic intestinal obstruction, caused by the passage of biliary calculus from
      vesicle to intestine, through fistulization, although not frequent, deserve study
      due to the morbi-mortality rates. Incidence in elder people explains the
      association with chronic degenerative diseases, increasing complexity in terms of
      therapy decision. Literature discusses the need and opportunity for the one or
      two-phase surgical attack of the cholecyst-enteric fistule, in front of the
      resolution on the obstructive urgency and makes reference to Gallstone Ileus as
      an exception for strong intestinal obstruction. The more frequent intestinal
      obstruction observed is when it occurs a Gallstone Ileus impacting in terms of
      ileocecal valve. The authors submit a Gallstone Ileus manifestation as causing
      strong intestinal obstruction, discussing aspects regarding diagnostic and
      treatment.

PMID- 8578084
TI  - Pulmonary cancer and hypertrophic osteoarthropathy. Brief recurrence of the
      osteoarticular symptoms after surgical resection.
AB  - A case of adenocarcinoma of the lung in a 57 years old patient associated with
      hypertrophic osteoarthropathy is reported by the authors. The paraneoplastic
      manifestation occurred after the pulmonary symptoms and receded spontaneously
      after a right inferior lobectomy was performed. Osteoarticular symptoms returned
      near after a tumoral recurrence. Articular pains disappeared 48 hours after the
      tumoral recurrence resection of the chest wall and clubbing disappeared
      completely after the 3rd. week.

PMID- 8578085
TI  - Secondary rhinoplasty: reconstitution of the allar cartilage by a rhinoplasty
      with an external incision.
AB  - Presentation of 62 cases of secondary nasal deformities treated by external
      incision. Several types of endonasal deformities were observed, properly
      classified and repaired. When excessive resection was observed, local cartilage
      graft, septonasal or conchal types were employed.

PMID- 8578086
TI  - Cervical evidement: classification and nomenclature.

PMID- 8578087
TI  - [Who should avoid practising sports?].

PMID- 8578089
TI  - [Alcohol-smoking interaction in hepatic lesions].
AB  - The consequences upon the liver of the simultaneous action of alcohol and of
      tobacco smoke substances were evaluated. The clinical and biochemical alterations
      shown by 18 alcoholics non smokers were compared to those shown by 36 alcoholics
      smokers, taken from a population of 189 male patients admitted into a psychiatric
      hospital for alcoholism treatment. The smokers, relative to the non smokes, had
      lower average age and earlier onset of alcoholism, drank greater quantities of
      alcohol per day and in shorter periods, and showed between others biochemical
      plasmatic alterations, more elevated levels of aspartate aminotransferase (with
      AST/ALT ratio greater) and alkaline phosphatase, suggestive of more pronounced
      hepatic aggression.

PMID- 8578088
TI  - [Sodium diclofenac effect, after interruption of the stercoraceous peritonitis,
      on the rat colon. Study of mechanical resistance and collagen concentration].
AB  - The objective of the present study was to investigate changes in colon wall in
      rats with fecal peritonitis (Per) associated with sodium diclofenac (SD) by
      studying breaking strength and tissue collagen concentration. The rats were
      divided into the following experimental groups: GROUP 1-SD: 60 animals injected
      intramuscularly with sodium diclofenac at the dose of 2 mg/kg body weight; GROUP
      2-Per: 60 animals injected intraperitoneally with a suspension of human feces.
      Peritonitis was interrupted after six hours of evolution; GROUP 3-Per+SD: 60
      animals injected intraperitoneally with a suspension of human feces and receiving
      SD according to the schedule used for Groups 1 and 2; CONTROL GROUP: 12 animals
      injected intramuscularly with physiological saline. The animals of Group 1, 2 and
      3 were successively sacrificed 2, 4, 7, 14 and 21 days after interruption of
      peritonitis an/or the beginning of treatment. Under conditions of the
      experimental model and of the methods used, we conclude that sodium diclofenac,
      peritonitis and the peritonitis-sodium diclofenac association decrease the
      breaking strength and the concentration of tissue collagen in the colon segment.

PMID- 8578090
TI  - [Action of elastic compression on valvular closing time].
AB  - The study was carried out in ten patients with venous insufficiency of limbs
      verified by clinical standards, photopletismography and descending venogram
      witch, previous venous stasis ulcer and branquial/ankle doppler index greater
      than 0.9. The valvular closing time (VCT) was measured with Duplex scanning, at
      the level of popliteal vein bellow de lesser safenous vein entrance. The ten
      patients showed an initial VCT greater than 0.5 sec, with the utilization of the
      elastic compression and new measurement of VCT, seven showed a normalization of
      VCT (valves lower than 0.5 sec). The elastic compression of limbs is efficient in
      reducing the venous reflux and it could be evaluated individually with a non
      invasive test--The Duplex scanning.

PMID- 8578091
TI  - Identification of heterogenous motility patterns of the stomach in duodenal ulcer
      disease.
AB  - This study aims to compare gastric emptying of solid meals in two different
      duodenal ulcer populations and their respective control groups. The same authors,
      utilized the same methods, but on different occasions. Four study groups were
      composed as follow: DU I--15 patients, CI--12 patients, DU II--16 patients, C II-
      15 patients. All individuals underwent high gastrointestinal tract evaluation.
      Endoscopy was normal in all subjects of the control groups. The ulcers were
      active but without reducing of the duodenal lumen. Gastric emptying was studied
      with the use of 30 grams of Tc tagged chicken liver. Measurements of Gastric
      emptying were taken by a gamma camera Ohio-series ON-150) with 15 minutes
      intervals during 120 minutes. Emptying rates expressed as percent of the test
      meal remaining in the stomach were submitted to KRUSKAL-WALLIS STATISTICAL
      analysis at each time and were identical in the groups, DU I, C I and C II.
      Emptying rates were significantly lower in the DU II group compared to the
      others. This study permits us to conclude that the gastric emptying in duodenal
      ulceration can be normal or delayed for reasons not clearly understood.

PMID- 8578092
TI  - [Effect of omeprazole administration on pancreatic content of enzymes in rats].
AB  - Gastric chloride acid plays an important role in pancreatic enzyme synthesis and
      secretion, mediated by cholecystokinin released in the duodenum. This study was
      designed to evaluate the influence of gastric acid suppression by omeprazole on
      pancreatic enzyme content. Eighteen male Wistar rats (180-220 g) were divided in
      two groups: I--control and II--omeprazole. Animals received by intraduodenal
      catheter 3 doses of 0.5 ml saline solution (NaCl 0.9%)--Group I or 5 mumol/Kg of
      omeprazole solution--Group II at 24 h intervals. All animals, after an overnight
      fasting period, were killed 3 h after the last dose. Serum amylase and pancreatic
      tissue content of protein, trypsinogen, elastase, lipase and phospholipase A2
      were determinated. Omeprazole treated animals (group II) showed statistically
      significant lower levels of serum amylase and pancreatic trypsinogen content (P <
      0.05). We believe that this effect is related with acid secretion suppression by
      omeprazole and that it may be mediated by cholecystokinin.

PMID- 8578093
TI  - [Comparative study of arginine and glutamine supplements in malnourished surgical
      patients].
AB  - Protein-calorie malnutrition is frequently diagnosed in patients with serious
      digestive conditions displaying obstructive symptoms, notably in esophageal
      cancer. In the present study a homogeneous group of subjects affected by
      esophageal cancer and candidates for elective surgery was randomly treated by one
      of the following oral supplements: arginine (group I), glutamine (group II), or
      mixed commercial amino acids (Group III-controls). The methods included
      nutritional measurements (biochemical and anthropometric assement), immunologic
      survey (skin tests), and general clinical and surgical findings, with emphasis on
      surgical morbidity. Body weight remained stable throughout the study, whereas
      serum albumin, total lymphocytes and skin tests tended to improve in all groups,
      with statistical confirmation for albumin in arginine-treated cases (group II).
      Post-operative hospitalization was numerically shorter during glutamine
      supplementation, and this trend was statistically significant when total
      morbidity was compared between the groups. It is concluded that: 1) Malnutrition
      and anergy were a major problem in this population, with equally severe post
      operative morbidity; 2) Administration of arginine enabled serum albumin levels
      to improve; 3) Glutamine-treated subjects displayed reduced post-operative
      morbidity; 4) No side effects could be attributed to the therapy here employed.

PMID- 8578094
TI  - [Serotypes of pneumococci isolated from children with pneumonia: implication of
      pneumococcal specific immunization].
AB  - For the 15 years from 1978 to 1992 serologic typing was performed on 124
      pneumococcus isolates from children with acute pneumonia. The source of bacteria
      was material obtained by aspirative pulmonary punction, pleural fluid or blood;
      122 capsular antigens representing groups and types could be determined. Of the
      122 isolates serogrouped 14, 1, 6, 5, 4, 7, 23, 19 and 4, accounted for 25.4%;
      23.8%; 13.1%; 9.0%; 4.9%; 4.9%; 4.1%; 4.1%; 4.1%; respectively, of cases. The
      currently available 23-valent vaccine would provide protection against 89.3% of
      identified pneumococci in our study, but because of its poor immunogenicity in
      children less than 2 years old (73.0%) they would have received reduced
      protection by the use of this vaccine. The distribution of pneumococci serogroups
      found in our study has an intermediary pattern in relation to those found at
      develop countries (6, 14, 18, 19, 23) and developing ones (1, 2, 3, 5, 7, 12,
      46). The new conjugate vaccines, with limited number of pneumococcal
      groups/types, should be analysed before the introduction in different geographic
      areas.

PMID- 8578095
TI  - [Abdominal aortic aneurysm infected with Campylobacter fetus spp fetus. Report of
      a case and review of the literature].
AB  - Aortic aneurysm infected with Campylobacter fetus spp fetus is rare, the first
      case having been reported in 1971. We present a case of abdominal aortic
      aneurysm, with a history of abdominal pain, fever and chills, with identification
      of this gram negative bacillus in the culture of the aortic wall and
      visualization of the microorganism in histological examination. Surgical
      correction was performed by interposition of a dracon prosthetic graft. The
      patient had a good postoperative course, receiving prolonged antibiotic therapy
      (intravenous cephalothin for 7 days and oral erythromycin for 6 months),
      remaining without symptoms for 12 months, when the follow-up was ended. In the 11
      cases reported in the literature, 9 presented fever, suggesting the infectious
      etiology. Four were operated on with the aneurysm already ruptured and all of
      them died. The other patients, with non-ruptured aneurysms at the time of the
      operation, were all symptomatic, and they survived. Anatomic reconstruction was
      performed in 4 cases, with dacron graft interposition and antibioticotherapy,
      without reported signs of infection on the follow-up (6 to 45 months). Aortic
      infection with Campylobacter fetus spp fetus is potentially fatal, needing
      immediate surgical treatment. It is possible to have good long term results with
      an anatomically placed prosthetic graft and antibiotic therapy.

PMID- 8578096
TI  - [Splenic cyst. Review of the literature and report of 2 cases].
AB  - Splenic cysts are rare lesions. By 1978, only 651 cases had been reported. Over
      the years, the management of splenic cysts has changed with advances in surgical
      techniques. The traditional treatment of these lesions has been splenectomy. The
      recognition of the post splenectomy complications has led to emphasis on
      conservation of splenic tissue. Nowadays, the tendency is to use splenic salvage
      techniques: partial splenectomy, partial splenic decapsulation and laparoscopic
      assistance. The purpose of this paper is to review the literature, and to report
      two cases of splenic cysts that were treated by the conservative method.

PMID- 8578097
TI  - [Medicine and statistics].
AB  - Doctors as researchers often resort to hypothesis testing and confidence
      intervals in the statistical analysis of study results. On the one hand, the use
      of statistical software has made this task easier. On the other hand, this has
      not contributed to neither a better understanding of statistical concepts nor to
      a seminal cooperation between doctors and statisticians. This note shows that the
      classical statistical theory, also called frequentist or Fisherian, offers
      probability statements that are very indirect ones. Bayesian statistics, on the
      other hand, gives a probability statement which is a more direct answer to the
      research question. Of course, this latter approach would hardly be considered
      without a close cooperation with an statistician. An improvement in the meaning
      of the probability statements may be seen as a gain in quality. An effective
      cooperation with statisticians, an issue that is more ethical than
      methodological, is directed to achieving a research of a better quality, so
      avoiding the scandal of poor medical research.

PMID- 8578098
TI  - Relationship between the development of pulmonary fibrosis and lung tumors in
      Syrian golden hamsters induced by N-methyl-N-nitrosourethane.
AB  - To cast light on the relationship between the development of pulmonary fibrosis
      and lung cancer, female Syrian golden hamsters were given 5 sc injections of 0.6
      mg/animal of N-methyl-N-nitrosourethane (MNUR) at 2-wk intervals and then
      maintained without any treatment for 26 wk. Bronchiolo-alveolar cell tumors and
      hyperplasias, which were recognized from week 4 after termination of treatment,
      were each subdivided morphologically into 3 types. Bronchiolo-alveolar cell
      tumors included papillary tumors consisting of basophilic cells, papillary tumors
      consisting of clear cells, and papillary/solid tumors consisting of pleomorphic
      cells, with papillary tumors consisting of basophilic cells predominating.
      Bronchiolo-alveolar cell hyperplasias encountered were glandular metaplasia,
      simple hyperplasia, and papillary hyperplasia. Glandular metaplasia was the most
      common of the hyperplastic lesions. To some extent, all the proliferative lesions
      were associated with inflammatory cell infiltration, but this varied greatly. The
      rate for papillary tumors consisting of basophilic cells with connective tissue
      proliferation was 35%. Among the hyperplastic lesions, the cell proliferative
      activity of papillary hyperplasia (12.5%) was significantly higher than in other
      hyperplastic lesions, suggesting that this lesion might be a preneoplastic
      change. None of the lung proliferative lesions showed any unequivocal
      immunoreactivity for the p53 protein. The present study suggests that most lung
      tumors may develop from pulmonary inflammatory lesions induced by MNUR, but the
      possibility that DNA injuries to the respiratory epithelial cells by MNUR may
      cause lung tumors cannot be precluded.

PMID- 8578099
TI  - Rapid induction of preneoplastic liver foci in embryonal turkey liver by
      diethylnitrosamine.
AB  - Diethylnitrosamine (DEN) was injected into fertilized turkey eggs. After
      incubation for 24 days, the livers of the embryos were removed and investigated
      by means of histological and enzyme-histochemical methods. Doses of 2 and 5 mg
      DEN per egg had no effect on mortality and embryo weight but induced various
      types of foci of altered hepatocytes. In addition, a replacement of the
      trabecular structure of the liver by a tubular arrangement of the hepatocytes and
      markedly enlarged hepatocytes were found. The diethylnitrosamine-induced foci of
      altered hepatocytes were very similar to the preneoplastic lesions that occur in
      the liver of mammals during hepatocarcinogenesis and are regarded as early
      indicators of carcinogenicity. The presented in ovo model is a simple (1 dose),
      rapid (24 days), and inexpensive (no animal housing) approach for the induction
      of foci of altered hepatocytes. The sensitivity of this carcinogenesis bioassay
      appears to be comparable to that of lifetime studies in rodents. It is proposed
      that the induction of preneoplastic foci of altered hepatocytes in ovo is a
      valuable screening model for hepatocarcinogenic effects.

PMID- 8578100
TI  - Longevity, body weight, and neoplasia in ad libitum-fed and diet-restricted
      C57BL6 mice fed NIH-31 open formula diet.
AB  - Groups of C57BL6 mice of each sex were assigned to one of 2 dietary regimens, ad
      libitum (AL) or dietary restriction (DR), to study effects of food restriction on
      body weight, survival, and neoplasia. The AL and DR groups were subdivided into a
      scheduled sacrifice group for examination at 6-mo intervals, and a lifetime group
      to provide longevity data. Necropsies and microscopic examinations were conducted
      on 911 animals. In the lifetime group food consumption averaged 33.6 and 34.4 g
      per week by AL males and AL females, respectively; the DR counterparts were given
      40% less. The diet contained 4.35 kcal/g. The average lifetime body weights were
      34.8, 26.8, 22.6, and 21.6 g for AL males, AL females, DR males, and DR females,
      respectively, and their age at 50% survival was 27.5, 26.9, 31.7, and 33.5 mo.
      Maximal lifespan was increased 18% in DR males and females. Lifetime incidence of
      tumor-bearing mice was 89% and 86% for AL males and females, versus 64% for each
      sex of DR mice. Dramatic reduction occurred in female DR mice in lymphoma (9% vs
      29%), pituitary neoplasms (1% vs 37%), and thyroid neoplasms (0.4% vs 8%). In
      males, hepatocellular tumors were reduced to 1% from 10% by DR. In contrast, the
      incidence of histiocytic sarcoma was increased in DR females and unaffected in DR
      males. Tumor onset was delayed in DR animals; 87% of all neoplasms in males and
      95% in females had occurred in the AL mice by 24 mo, whereas the DR animals had
      only 52% and 39% of their lifetime incidence, respectively, by that age. This
      study provided comparative AL and DR data from C57BL6 mice examined randomly at 6
      mo intervals (cross-sectional group) in parallel with data from animals in
      similar cohort that was unsampled and allowed to succumb naturally (longevity
      group). Dietary restriction reduced the lifetime percentage of tumor-bearing
      animals and the number of tumors per animal, and delayed the age at onset of most
      neoplasms.

PMID- 8578101
TI  - Comparative changes in the liver of female Fischer-344 rats after short-term
      feeding of a semipurified or a semisynthetic L-amino acid-defined choline
      deficient diet.
AB  - Groups of female Fischer-344 rats were fed a semipurified choline-deficient (CD)
      diet, or a semisynthetic L-amino acid-defined choline-deficient (CDAA) diet, for
      up to 12 wk and effects of the 2 diets on the liver were compared. Steatosis was
      diffuse and more severe throughout in rats fed the CDAA diet than in rats fed the
      CD diet. Greater elevations in serum aspartate and alanine aminotransferase
      activities were also present in the former rats, along with higher 2
      bromodeoxyuridine labeling indices in the liver. Discrete amounts of 8
      hydroxyguanine were detected in liver DNA, but were not significantly different
      in rats fed the 2 diets, or from those present in a group of control rats killed
      at 0 time. Glutathione S- transferase placental form-positive focal lesions were
      not observed in any of the rats. The results show that the CDAA diet causes more
      severe degrees of steatosis and liver cell death and proliferation than the CD
      diet, raising the possibility that it may, in contrast to the CD diet, result in
      the eventual induction of hepatocellular carcinomas in female Fischer-344 rats.

PMID- 8578102
TI  - Sequential appearance and ultrastructure of amphophilic cell foci, adenomas, and
      carcinomas in the liver of male and female rats treated with
      dehydroepiandrosterone.
AB  - Dehydroepiandrosterone (DHEA), a hormone of the adrenal cortex, acts as a
      peroxisome proliferator and hepatocarcinogen in rats upon long-term treatment
      with high doses in the diet. The aim of the present study was to identify the
      site of origin of hepatocellular neoplasms and the sequence of preneoplastic
      lesions. Twenty-five female and 25 male rats were given 0.6% DHEA in the diet; 25
      animals of each sex were controls. Groups of 5 treated and untreated animals were
      sacrificed after 4, 20, 32, 70, and 84 wk. Amphophilic cell foci were detected
      after 32 wk of treatment; they developed from the liver parenchyma almost
      exclusively in the vicinity of portal tracts. Adenomas of the amphophilic or
      amphophilic/tigroid cell phenotype were observed at 70 wk of treatment. Highly
      differentiated hepatocellular carcinomas presenting a similar cellular phenotype
      occurred after 70-84 wk. The incidence of hepatocellular carcinomas was 44% in
      female and 11% in male rats. Ultrastructural studies of the amphophilic cell foci
      and tumors revealed a marked proliferation of mitochondria and a moderate
      proliferation of peroxisomes in all lesions. In addition, a very strong
      peroxisome proliferation was observed in perivenular hepatocytes in the liver of
      female rats. Peroxisomes usually lacked core and showed flocculent matrices. In
      male rats, weak peroxisomal proliferation was observed. Typical morphological
      abnormalities of these peroxisomes were paracrystalline inclusions of striated
      appearance. Although the most prominent peroxisome proliferation was observed in
      perivenular hepatocytes, these cells did not seem to be involved in tumor
      development. In contrast, the morphological similarity of the amphophilic cell
      foci and the amphophilic/tigroid cell adenomas and carcinomas, their coincident
      localization near portal tracts, and the sequential appearance of these lesions
      suggest that the amphophilic cell foci represent an early stage in DHEA-induced
      hepatocellular neoplasia. Mitochondrial proliferation as the most prominent
      feature in all stages of this model of hepatocarcinogenesis may offer a new
      approach for analysis of hepatocarcinogenesis induced by DHEA and possibly other
      peroxisomal proliferators.

PMID- 8578103
TI  - Effect of methimazole on rat renal carcinogenesis induced by N-ethyl-N
      hydroxyethylnitrosamine.
AB  - The effect of methimazole on N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced
      renal lesions was investigated in a medium-term initiation/promotion bioassay in
      male Wistar rats. EHEN-initiated rats underwent unilateral nephrectomy of the
      left kidney and subsequent addition of the renal tumor promoters trisodium
      nitrilotriacetate (NTA), potassium dibasic phosphate (PDP), or hydroquinone (HQ),
      alone or in combination with methimazole, to the diet for 20 wk. The addition of
      methimazole reduced the severity of simple and adenomatous renal hyperplasias
      induced by NTA, PDP, and HQ, but had no effect on the number of renal cell tumors
      that arose in EHEN+NTA groups. Methimazole also decreased the bromodeoxyuridine
      (BrdU) labeling indices, but had little effect on the expression of alpha 2u
      globulin in treated kidneys as compared to controls. It appears that methimazole
      exhibits antagonistic properties to nongenotoxic nephrotoxins, protecting against
      renal damage but not against tumorigenesis, probably arising from genotoxic
      insult.

PMID- 8578104
TI  - Histologic study of the femoral growth plate in beagle dogs.
AB  - The femora of normal-growing beagle dogs were examined histologically at 6 and 12
      mo of age to clarify the morphologic changes occurring in the femoral growth
      plate as background data for studies of chondrosseous toxicology. Enchondral
      ossification was active at 6 mo of age, and the growth plate disappeared at 12
      mo. The growth plate showed degradation of the matrix and destructive lesions at
      6 mo of age. Degradation of the matrix was observed between the chondrocytic
      columns accompanied by degeneration and disappearance of chondrocytes.
      Destructive changes were seen in the epiphyseal hyaline cartilage and
      proliferating and hypertrophic zones, resulting in disarrangement of the
      chondrocytic columns. Furthermore, abnormal chondrocytic proliferation of the
      epiphyseal hyaline cartilage zone and cleftlike fractures between the growth
      plate and cortex were frequently present. No abnormalities were detected in the
      articular cartilage at 6 and 12 mo of age.

PMID- 8578106
TI  - Registry of toxicologic pathology for animals.

PMID- 8578105
TI  - Cell death is alive and well.

PMID- 8578107
TI  - [How important is desensitization?].

PMID- 8578108
TI  - [Interventional cardiac catheterization in the very young].

PMID- 8578109
TI  - [Atherosclerotic renovascular disease and renal function].

PMID- 8578110
TI  - [Avicenna, physician and philosopher].

PMID- 8578111
TI  - [Bladder-sphincter disorders in patients with spinal cord injuries].
AB  - Improvement in the management of neuropathic bladders in spinal cord injury has
      considerably increased the life expectancy of these patients. The classical
      classification in central or peripheric neuropathic bladders, now leave place to
      a functional, clinical, and urodynamic classification. Three periods define the
      evolution of the neuropathic bladders: the initial period (drainage), the
      reeducation phase, and the stabilized period. Urodynamic investigations detect
      situations of risk (high intravesical pressures) and allow therapeutic
      adjustment. Intermittent catheterization has transformed neuro-urology and
      allowed deliberate choice of retention. Long term follow up is imperative
      (urodynamic study, echography, intravenous urography) to avoid secondary
      degradation.

PMID- 8578112
TI  - [Genital sexual and procreation disorders in patients with spinal cord injuries].
AB  - The first part of this report discusses techniques contributing to improved
      sexual relations in couples where either partner is paraplegic. The advantages
      and disadvantages of these techniques are described, in particular for
      intracavernous injections of vasoactive products. The second part considers
      procreative assistance for couples where the male is paraplegic, using
      mechanical, chemical and more recently surgical techniques. Surgery involves
      puncture of the ductus deferens. Significant experimental progress in medically
      assisted precreation is contributing to improved results. The importance of the
      psychological and emotional context must not be forgotten, as well as prevention
      of complications such as urological infections.

PMID- 8578113
TI  - [Pressure sore in patients with spinal cord injuries].
AB  - Pressure sore is a frequent and severe complication in spinal cord injured
      patients because of many specific risk factors. The patient must be responsible
      for his prevention program. An early and continuous education enables him to know
      the occurrence mechanisms of pressure sore and manage himself this prevention. A
      regular inspection of the risk areas is necessary and every beginning sore must
      lead to ask an advice from a specialist and to practice a complete check up.
      Wound healing may be obtained by an early and adequate treatment. If it is not
      the case surgical operation is necessary provided that a careful nursing is
      assured.

PMID- 8578114
TI  - [Neuro-orthopedic and muscle tonus disorders in patients with spinal cord
      injuries].
AB  - Heterotropic ossifications and contractures are frequent during evolution of
      spinal cord injury. Heterotopic ossifications occur in the first months following
      the acute state. Hip is the most common localisation. No preventive or curative
      treatment is available. At an early stage, clinical or instrumental (sonographic)
      diagnosis may prevent functional consequences. Muscular disbalance, incomplete
      physiotherapy, tonus disorders lead to contractures of limbs or trunk. They may
      have severe consequences on activities of dairy living. Surgical procedures may
      be necessary. Tonus disorders may resist to usual drugs. In this cases,
      intrathecal infusion of baclofen, injection of botulinus toxin, neurosurgery of
      orthopedic surgery may be useful.

PMID- 8578115
TI  - [Pain in paraplegic and tetraplegic patients].
AB  - Pain is a common complain in patients with spinal cord injury. Deafferentation,
      nociceptive stimuli and psychological component may both contribute in pain
      generating. Main importance of clinical evaluation may be pointed out since level
      of injury and complete or incomplete lesion may affect the expression of
      symptomatic pain and projection of neurological pain. Closed to symptomatic
      approach, pain treatment in spinal cord injured people consist in medical and
      rehabilitation. Chronic neurological pain remains still difficult and may take in
      account psychological factors.

PMID- 8578116
TI  - [Technical aids to patients with spinal cord injuries].
AB  - The purpose of technical aids is to compensate temporary and especially
      definitive functional disabilities in handicapped people. In medullary injured
      patients, technical aids are essential to preserve as much as possible the
      independence of paraplegics and particularly tetraplegic patients--activities of
      daily life such as eating, toileting, dressing, ambulation, car-driving, writing
      and environment control become hence forward possible. Technical aids
      prescription and adaptations depend for a large part not only on the localization
      of the lesion of the trauma but also of the goals, motivations and the
      environment of the disabled person.

PMID- 8578117
TI  - [Socio-professional and judicial aspects of traumatic paraplegia and
      tetraplegia].
AB  - Social integration in competitive employment reminds the main laws, the practical
      aspects with difficulties encountered, and insufficient results. Juridical
      aspects mean study of different parts of torts, physiological and economic.

PMID- 8578118
TI  - [Treatment of the future for spinal cord injuries].
AB  - Future therapy of spinal cord trauma is based on the careful analysis of
      pathophysiological phenomena secondary to the initial lesion. The toxicity of
      excitatory amino-acids, which is an early phenomenon, can be treated by specific
      antagonists. Axonal regrowth, which spontaneously occurs within days after the
      trauma must be supported by trophic factors on the one hand, and by blocking of
      the glial scar formation on the other hand. Finally, neuronal loss can be
      replaced by grafts either from embryonic neurons, or from genetically engineered
      cells, or direct gene therapy using viral vectors. Clinical applications are on
      their way for the early toxic phenomena, more remote for axonal regrowth and
      grafts. In any case, future treatment will have to use concurrently these three
      approaches, in specialized spinal units.

PMID- 8578119
TI  - [Infectious diseases during pregnancy (I). Diagnosis, prevention, fetal risks,
      therapeutical consequences].

PMID- 8578120
TI  - [Chronic obstructive bronchopneumopathies and their complications. Epidemiology,
      etiology, physiopathology, diagnosis, development, prevention, treatment,
      posology with oxygen therapy].

PMID- 8578121
TI  - [Retinal detachment. Etiology, diagnosis, preventive and curative management].

PMID- 8578122
TI  - [Dysphagia. Diagnostic orientation].

PMID- 8578123
TI  - [Non-traumatic coma in children. Diagnostic orientation].

PMID- 8578124
TI  - [Long-acting beta2-mimetics in asthma].

PMID- 8578125
TI  - [Genetic markers in cardiomyopathies].

PMID- 8578126
TI  - [Gradual loss of muscular strength in aging].

PMID- 8578127
TI  - [BCG-therapy of bladder tumors].

PMID- 8578128
TI  - [Drugs in 19th century France].

PMID- 8578129
TI  - [Epidemiology and etiology of acute digestive hemorrhage in France].
AB  - The epidemiology of gastrointestinal bleedings is poorly known in France. The
      principal source of bleeding comes from upper gastrointestinal tract. The most
      common etiology of upper gastrointestinal bleeding is peptic ulcer. Non steroidal
      anti-inflammatory drugs absorption is frequently associated with ulcer bleeding.
      The second most frequent etiology is variceal hemorrhage, complicating mostly
      alcoholic cirrhosis. The causes of lower gastrointestinal tract bleeding are more
      difficult to detect. The major causes are: colonic diverticula, angiodysplasias,
      traumatic ulcers of the rectum, colorectal carcinomas and colitis. In children,
      peptic ulcers and varices are the two main causes of upper gastrointestinal
      bleeding. Etiologies of lower gastrointestinal bleeding are varying according to
      the age: juvenile polyposis in children less than 6 years and Meckel's
      diverticulum after 6 years.

PMID- 8578130
TI  - [Natural history of esophageal varices and prevention of hemorrhage].
AB  - More than one third of cirrhotic patients will experience variceal bleeding, of
      whom two thirds will die. The most reliable predictive factor for variceal
      rupture is the presence of large oesophageal varices at upper endoscopy. Non
      cardio-selective beta blockers have been proved to be effective in preventing
      bleeding. Cirrhotic patients should therefore be entered in an endoscopy
      screening program. Should no varices or small varices be found in the oesophagus,
      endoscopy should be repeated every year. Patients found to have large varices
      should be given beta-blockers.

PMID- 8578131
TI  - [Treatment of digestive hemorrhages caused by rupture of esophagogastric varices
      in liver cirrhosis].
AB  - Bleeding from oesophageal and gastric varices is one of the most dramatic and
      important complications of cirrhosis. Non surgical options are favoured as first
      line treatment because the operative mortality in cirrhotic patients is high.
      These options include vasoactive drugs (terlipressin or somatostatin) and
      endoscopic treatment or a combination of these two treatments. Vasoactive drugs
      could be given before endoscopic treatment and perhaps even earlier during
      transfer to hospital to permit a therapeutic measure to be given at initial
      diagnostic endoscopy when bleeding is controlled and the patient stable. Balloon
      tamponade should be used only in patients with uncontrolled bleeding. Surgical
      portacaval shunt or transjugular intrahepatic portosystemic stent shunts is used
      as a second line treatment when all else has failed to control bleeding and
      because of an increased mortality risk surgery should never be too much delayed.

PMID- 8578132
TI  - [Treatment of digestive hemorrhages caused by non-cirrhotic portal hypertension].
AB  - Causes of gastrointestinal bleeding and principles for their treatment are very
      similar in non-cirrhotic portal hypertension to those in portal hypertension due
      to cirrhosis. When the cause of the block responsible for portal hypertension is
      a thrombogenic disorder, anticoagulation must be associated. The need for
      anticoagulation does not modify the general rules for management but may make it
      more difficult.

PMID- 8578133
TI  - [Therapeutic indications in hemorrhaging duodenal and gastric ulcers].
AB  - Ulcer complications including bleeding and perforation were increasingly observed
      during the last decade due to the greater life expectancy and the increased NSAID
      consumption. The unchanging mortality rate, which has been around 6-10% for
      several decades, could be explained by the fact that age and the prevalence of
      concurrent illness are important predictors of death. Rebleeding which is also an
      independent prognostic factor can be predicted by the presence of hypovolemic
      shock and of endoscopic stigmata such as active bleeding or a visible vessel.
      Endoscopic hemostatic therapy, specially injection therapy which is the most
      widely used method, has become the treatment of choice. It has been proven to
      significantly reduce rates of further bleeding, surgery and mortality. Surgical
      intervention is indicated in cases of immediate or secondary failure of
      endoscopic therapy (20%) and should not be delayed in high-risk patients. Once
      hemostasis has been achieved therapeutic goals are to heal the ulcer and to
      prevent the occurrence of further complications including bleeding and also
      perforation.

PMID- 8578134
TI  - [Gastroduodenal stress hemorrhage during intensive care].
AB  - Stress gastric erosions are in fact the gastroduodenal expression of a most
      disseminated injury involving whole organism. Ischemia represents the main factor
      leading to the decrease of gastric mucosa protective mechanisms. The most
      important complication of stress ulceration is acute bleeding. Gastrointestinal
      hemorrhages of clinical relevance are now so scarce that widespread systematic
      prophylaxis against stress ulcers can be safely withheld. Supportive therapy of
      associated acute organ failure remains the most accurate prophylaxis. Patients
      who are the most likely to benefit from specific prophylaxis are still unknown.

PMID- 8578135
TI  - [Diagnosis and treatment of colonic and anorectal hemorrhages].
AB  - In lower gastrointestinal bleeding, the first step is the exclusion of an upper
      gastrointestinal cause, responsible in 15 to 20% of cases, and the assessment of
      the severity of blood loss, so that an adequate resuscitation can be rapidly
      performed. Eighty percent of these bleeding episodes stop spontaneously; among
      these, 25% recurs, sometimes severely. When bleeding episode stops, it is
      essential to repeat the examinations to find out the cause of bleeding. The
      therapy may be endoscopic, radiologic, surgical or medical. For patients who
      require an emergent surgical procedure, intraoperative endoscopic techniques can
      be helpful. In 95% of cases, the source of bleeding is the colon or the rectum:
      the most common causes are diverticular disease, in particular from the right
      colon, colorectal tumours, angiodysplasia and colitis, but there are some simple
      causes easy to diagnose such as hemorrhoids, anal fissures and thermometric
      ulcerations.

PMID- 8578136
TI  - [Digestive hemorrhage undiagnosed by conventional endoscopy].
AB  - Digestive bleeding undiagnosed by conventional endoscopies occurs in about 5% of
      the patients with gastro-intestinal bleeding. Vascular ectasias are the most
      common cause. More than half of these tumors are benign. Meckel's diverticulum is
      the cause of bleeding in two thirds of men under the age of 30. Hemorrhage from
      the biliary tree or pancreatic duct occurs more often in patients with a
      suggestive history. According to the abundance and the cause of hemorrhage
      numerous investigations can be undertaken and the diagnostic value of new
      endoscopic methods (enteroscopy, endoscopic ultrasonography) must be assessed.

PMID- 8578137
TI  - [Malaria. Epidemiology, etiology, physiopathology, diagnosis, clinical course,
      prognosis, treatment, prevention].

PMID- 8578138
TI  - [Ankle trauma. Diagnostic orientation].

PMID- 8578139
TI  - [Cancer of the testis. Pathological anatomy, diagnosis, clinical course,
      prognosis, treatment].

PMID- 8578140
TI  - [Cystic fibrosis. Epidemiology, diagnosis, clinical course, prognosis,
      treatment].

PMID- 8578141
TI  - [Induced abortion. Legislation, epidemiology, complications].

PMID- 8578142
TI  - [K-ras oncogene in bronchial cancer. Its current prognostic role and long-term
      therapeutic perspectives].

PMID- 8578143
TI  - [Function of the endothelium in arterial hypertension].

PMID- 8578144
TI  - [Chronic active hepatitis].

PMID- 8578145
TI  - [The peacock feathers of Constantine the African].

PMID- 8578146
TI  - [Conversion hysteria].
AB  - Conversion disorder is characterized by symptoms or deficits affecting voluntary
      motor or sensory function that suggest a neurological condition. The symptoms or
      deficits are related to psychological factors but not intentionally produced or
      feigned. They could be associated with true neurological disorders and their
      diagnosis is difficult. Neurologically they do not conform to known neurological
      mechanisms but instead follow the individual conceptualization of a condition and
      vary according to attention and emotions. Psychologically they are related to a
      psychic conflict or a stressful event. They could be associated to other
      manifestations of the hysterical neurosis or various mental conditions.

PMID- 8578147
TI  - [Dissociative hysteria].
AB  - Under the term of dissociative hysteria are described a set of clinical syndromes
      characterized by behavioral disorders and psychic activity anomalies. The nature
      of the symptoms seems very similar to hysterical conversion. Psychogenic amnesia,
      psychogenic fugues and multiple personality disorder are described. There is some
      evidence that the symptoms are related to psychic affective traumatisms and no
      physiological alteration. Two mechanisms are proposed: dissociation of
      personality and amnesia. Clinical course generally improves spontaneously.
      Various forms of psychotherapy may be used.

PMID- 8578148
TI  - [Hysteria in children].
AB  - Hysteria can be found in childhood but as all nevrotic problems during the life
      period, it is not a fixed entity and cannot presume for the personality to come.
      Diagnosis is often difficult and is mostly made in pediatric unit in front of
      conversions symptomatology. The difference between transitory somatizations
      (frequent during childhood) and conversions is important to make. As part of the
      diagnosis, finding the underlying personality is necessary. Hysteria is mostly
      found during the latency period and around puberty period. Awareness is important
      when the diagnosis is made, to be sure to recognize all the cases and only the
      real one. Two common situations could be isolated: 1. when a symptom cannot be
      related to a somatic disorder; 2. when the seduction behavior of a maiden creates
      counter-attitudes of the medical team and family.

PMID- 8578149
TI  - [Hysterical personality disorder].
AB  - The hysteric personality disorder is characterized by: 1. an intense need for
      affection; it is a child-like need, seeking protection and affection, making the
      patient subject to suggestibility and dependence, along with an erotic behaviour
      which is in reality associated to fear of sexuality; 2. an exaggerated and
      rapidly shifting expression of emotion leading to unstable, theatrical and
      histrionic expression of emotions giving an impression of shallowness and lack of
      authenticity; 3. a highly imaginative thinking pattern with flight of reality and
      tendency to dreaming, mythomania, memory reconstruction.

PMID- 8578150
TI  - [The borders of hysteria].
AB  - Medical writing dealing with the nosology of hysteria has evolved through
      successive national and international classifications, while in parallel the
      expression of hysteria has changed with time, with cultural evolution and with
      increased medical knowledge. Hysteria, by definition, is distinguished both by
      psychic or physical symptoms reported or voluntarily induced by patients
      (simulation or pathomimic behaviour) and by somatic disorders having an
      underlying, associated organic pathology, favoured by an emotional context or a
      conflictual situation (psychosomatic disorders). The divergence, but above all
      the analogies between hysterical symptoms and such limits are underlined, showing
      the frequency of succession with time, associations and transitional forms
      ("somatisation disorder" of the DSM III, psychogenic pain, and psychosomatic
      disorders termed "psychofunctional").

PMID- 8578151
TI  - [Hysterical emergencies].
AB  - Most probably common in emergency departments, but still not well studied in this
      context, the disorders formerly called "hysteria" are now included in the group
      "Somatization, undifferentiated somatoform, conversion and dissociative
      disorders" (SSCD disorders) DSM IV. Their common presentation is that of
      idiopathic somatic symptoms linked with mental disorders. In the emergency
      department these symptoms confront physicians who generally do not have extensive
      psychiatric training. The symptoms occur, and disappear, undetermined by the
      patients, who are genuinely ill and not malingering. Aside from the somatisation
      disorder, which by definition is chronic, invalidating and rare, the other
      disorders (SCD) can: be contingent on the picture of another acute, easily
      recognisable mental disorder; or, on the other hand, be highly reactional and
      transient; or constitute the "somatic presentation" of an anxious disorder, the
      panic attack, well known in somatic emergencies. Management is based on
      diagnostic considerations and by the difficulties of the patient to accept a
      psychic cause of the symptoms whereas he is experiencing an organic disorder. The
      possibilities of discussing such psychogenesis in the context of the emergency
      department are slight, and the best course is often to adopt a pragmatic and
      prudent medical approach. An essential point is respect of the patient and his
      ideas. The legal provision, which already exists, for the presence of
      psychiatrists in emergency departments should lead to physician-psychiatrist
      cooperation that would be beneficial for these patients.

PMID- 8578152
TI  - [Suggestion and hypnosis in hysteria].
AB  - Suggestive influences allow to resolve ambiguities. Normally they are only
      accepted if they correspond with the knowledge and believes of the subject. Under
      hypnosis or under the impact of serious psychic perturbations one may take up
      reality constructions which are not in conformity with these criteria. The
      restriction of consciousness and the ignoring of certain functions permitting
      this are the common basis of hypnosis and hysteria. But suggestions do not cause
      the later; they may only shape the symptomatology. Hypnosis can create a terrain
      facilitating the resolution of the problems underlying hysteria but it does not
      represent the treatment of hysteria.

PMID- 8578153
TI  - [Treatments of hysteria].
AB  - Treatment of hysteria requires establishing a management strategy. The first
      steps consist of symptomatic treatment (catharsis, counter-suggestion, hypnosis,
      narco-analysis, relaxation, focused psychoanalytical psychotherapy, drug
      therapy). Thereafter, an approach aiming to modify the psychic structure of the
      patient can be considered (supportive psychotherapy, psychoanalysis).
      Occasionally, a systemic approach is necessary. Although each facet of the
      treatment must be conducted by a specialist, one physician must supervise the
      overall strategy; this role falls naturally to the family doctor.

PMID- 8578154
TI  - [Increased erythrocyte sedimentation. Diagnostic orientation].

PMID- 8578155
TI  - [Tumors of the bladder. Pathological anatomy, etiology, diagnosis, clinical
      course].

PMID- 8578156
TI  - [Acute prostatitis. Etiology, diagnosis, clinical course, prognosis, treatment].

PMID- 8578157
TI  - [Pregnancy. Diagnosis, clinical monitoring, indications for complementary
      examinations, legislation].

PMID- 8578158
TI  - [Non-traumatic coma. Diagnostic orientation].

PMID- 8578159
TI  - [Hemiplegia. Diagnostic orientation].

PMID- 8578160
TI  - [Nutritional requirements for infants, children and pregnant or breast-feeding
      women. Energy, iron, proteins, essential fatty acids, vitamin D, calcium].

PMID- 8578161
TI  - Diffuse esophageal spasm: a malfunction that involves nitric oxide?
AB  - OBJECTIVE: As recently suggested, nitric oxide (NO) may play an important role in
      the regulation of esophageal motility, being partly responsible for the latency
      period and latency gradient between the onset of a swallow and contractions of
      esophageal circular smooth muscles. Diffuse esophageal spasm appears to be a
      classical example in which the mechanisms normally responsible for the
      physiologic timing of the contractions occurring in the esophageal body after
      swallowing are disturbed. METHODS: Five patients (one male and four female; age,
      18-48 years) with symptomatic esophageal spasm were give glyceryl trinitrate
      (GTN) intravenously in gradually increasing doses or L-arginine on two separate
      occasions and underwent manometric measurements of esophageal motility after wet
      swallows, using a multilumen perfused catheter system (Synetics Medical,
      Stockholm, Sweden). The amplitude, duration, and propagation of the contractions
      and the latency period were analyzed, using specially designed software.
      Additionally, during the GTN infusion period arterial blood pressure was measured
      every 5 min, RESULTS: GTN infusion given at a dose of 100 to 200 micrograms/kg-h
      intravenously caused the occurrence of and a dose-dependent elongation of the
      latency period after swallowing. The mean amplitude of the contractions did not
      show any significant alterations, whereas the mean duration of the contractions
      decreased significantly, from 11.2 +/- 4.8 sec to 5.4 +/- 0.8 sec. These effects
      were accompanied by significant alleviation of symptoms during swallowing.
      Interestingly, no adverse side effects such as headache or flush were observed at
      any dose of GTN. The blood pressure did not show any changes during the studies
      in any of the five patients. Administration of L-arginine (300 mg/kg-h
      intravenously) did not cause any significant alterations of motility pattern or
      alleviation of dysphagia. CONCLUSIONS: 1) NO may play an important role in the
      control of human esophageal motility, being involved in the mechanisms
      responsible for the timing of propulsive contractions in the body after
      swallowing; 2) GTN may to be of benefit in the treatment of diffuse esophageal
      spasm in symptomatic patients; and 3) patients with diffuse esophageal spasm may
      have a malfunction in endogenous NO synthesis and/or degradation.

PMID- 8578162
TI  - Well-being and gastrointestinal symptoms among patients referred to endoscopy
      owing to suspected duodenal ulcer.
AB  - BACKGROUND: Few studies have evaluated quality of of life (QoL) in patients with
      upper gastrointestinal diseases, and there is a lack of validated measures for
      use in gastroenterology. METHODS: The applicability and relevance of self
      administered questionnaires such as the Psychological General Well-Being (PGWB)
      index and the Gastrointestinal Symptoms referred to endoscopy because of
      suspected duodenal ulcer were evaluated. RESULTS: In total, 1526 patients with
      suspected duodenal ulcer were screened for inclusion in a clinical study. On the
      basis of medical history and endoscopy, 1424 patients who completed the
      questionnaire before endoscopy were classified in five diagnostic groups:
      oesophagitis, gastric ulcer, duodenal ulcer, negative endoscopy, and gastritis
      duodenitis. Irrespective of diagnosis, all patient groups reported a considerable
      decrease in their general well-being (mean score, 85, compared with 105 in
      healthy populations) with no significant differences between the groups. The
      results of the GSRS, however, showed statistically significant differences
      between the groups in dimensions depicting Abdominal pain, Reflux, Indigestion,
      and Diarrhoea Syndrome. CONCLUSIONS: The results of the study showed that,
      irrespective of endoscopic findings, patients complaining of upper
      gastrointestinal symptoms have a low degree of general well-being. The symptoms
      profiles in the different diagnostic groups vary considerably.

PMID- 8578163
TI  - Lansoprazole capsules and amoxicillin oral suspension in the treatment of peptic
      ulcer disease.
AB  - BACKGROUND: Lansoprazole is a potent antisecretory drug also possessing anti
      Helicobacter pylori activity in vitro. It is a candidate drug for combination
      regimens with antibiotics for treating H. pylori infections. METHODS: In a
      semiblind study, 65 patients with duodenal and/or gastric ulcer and pathologic
      14C urea breath test results were treated with either 60 mg lansoprazole every
      morning only for 14 days or combined with 500 mg amoxicillin oral suspension four
      times daily between meals, given for 11 days. Endoscopy and breath test were
      repeated after 6 weeks and 6 months. Patients with unhealed ulcers were
      withdrawn. RESULTS: Eradication of H. pylori infection was attained in 46% of
      patients receiving lansoprazole and amoxicillin but in no patient receiving
      lansoprazole alone. Ulcers healed significantly more often in those who were H.
      pylori-negative (18 of 19 (95%)) than in those who were H. pylori-positive (20 of
      41 (49%)). Adverse events, particularly stomatitis/sore throat and diarrhea,
      occurred significantly more often when amoxicillin was combined with
      lansoprazole. CONCLUSIONS: Lansoprazole eradicated H. pylori infection only when
      combined with amoxicillin. Eradication rates in this study are hardly acceptable,
      and further studies are necessary to define optimal doses and duration of
      treatment. Using amoxicillin as an oral suspension may not be of any substantial
      benefit and may cause stomatitis and sore throat.

PMID- 8578164
TI  - A simple, rapid, and highly reliable capsule-based 14C urea breath test for
      diagnosis of Helicobacter pylori infection.
AB  - BACKGROUND: Since the urea breath test (UBT) indirectly detects gastric
      Helicobacter pylori infection by measuring urease activity, the possibility of
      false-positive results due to other urease-producing bacteria cannot be excluded.
      Previous studies have shown that increased 14CO2 activity in early breath samples
      could be attributed to urea hydrolysis in the oropharynx. For that reason,
      reliable assessment of H. pylori status is hampered for at least 20 min after
      administration of a 14C-urea drink. METHODS: To overcome this problem we have
      developed a modified breath test in which 111kBq 14C-urea is supplied in a
      gelatin capsule, which prevents release of 14C before reaching the stomach. Our
      modified 14C UBT was evaluated in 100 healthy volunteers, and results were
      compared with those from enzyme-linked immunosorbent assay serology. RESULTS: The
      study showed a 99% concordance between the two noninvasive tests. When a
      biometric method for determination of cut-off values between positive and
      negative UBT results with the smallest possible arbitrariness was used, the
      calculated statistical probability of a false diagnosis was lowest in the 10-min
      breath sample (0.20%), and 100% sensitivity and specificity was achieved. Our
      capsule method was also compared with the urea drink method and was found more
      reliable because no overlapping in 14CO2 activity occurred between H. pylori
      positive and -negative subjects, whereas conventional breath testing showed
      overlapping during the whole 30-min test period. Our study also showed that a
      fatty test meal lowers the 14CO2 excretion the first 20 min and may adversely
      affect the accuracy of a rapid UBT. CONCLUSIONS: Supplying the 14C-urea in a
      capsule obviates the problem of false-positive results in early breath samples
      and makes it possible to diagnose H. pylori infection with 99.8% reliability from
      a single 10-min breath sample, without the use of a test meal of adjustments for
      assumed individual CO2 production.

PMID- 8578165
TI  - Serum gastrin and mucosal somatostatin in Helicobacter pylori-associated
      gastritis.
AB  - AIMS: The aims were to study gastrin concentrations and gastric mucosal
      somatostatin and gastrin concentrations in relation to the extent of gastritis in
      Helicobacter infection. METHODS: We measured basal serum gastrin concentrations
      in antral mucosal biopsy specimens and somatostatin concentrations in corpus
      biopsy specimens in 88 consecutive dyspeptic subjects undergoing endoscopy. These
      subjects were divided into three categories on the basis of histology, serology,
      and culture: H. pylori-positive pangastritis, H. pylori positive antral gastritis
      with normal body histology, and H. pylori-negative controls. Statistical
      evaluation was done with the Wilcoxon rank sum test. RESULTS: Basal serum gastrin
      concentrations were significantly increased only in subjects with pangastritis
      and not in those with antral gastritis only, as compared with controls (mean +/-
      SEM: 72 +/- 7, 46 +/- 10, and 42 +/- 7 ng/l, respectively). Subjects with
      pangastritis or antral gastritis had significantly lower antral somatostatin
      concentrations than controls (mean +/- SEM: 0.80 +/- 0.07, 1.03 +/- 0.15, and
      2.40 +/- 0.31 micrograms/g(protein), respectively). We also found significantly
      lower antral gastritis only as compared with controls (mean +/- SEM: 62 +/- 13,
      78 +/- 16, and 165 +/- 25 micrograms/g(protein), respectively). In subjects with
      pangastritis a significantly lower concentration of somatostatin was found in the
      corpus biopsy specimens than in those with antral gastritis only and controls.
      CONCLUSIONS: These results suggest that hypergastrinemia in H. pylori gastritis
      is not caused by antral gastritis and antral somatostatin deficiency alone but
      that corpus inflammation plays a key role in the origin of hypergastrinemia.
      Furthermore, in patients with pangastritis a corpus mucosal somatostatin
      deficiency was found.

PMID- 8578166
TI  - Gastric relaxation in response to a soup meal in healthy subjects. A study using
      a barostat in the proximal stomach.
AB  - BACKGROUND: Meal-induced relaxation of the proximal stomach can be investigated
      by means of a barostat. Using a standard liquid meat soup that elicits symptoms
      and a wide antrum in patients with functional dyspepsia, we aimed at finding the
      best meal size and fat load for studying gastric relaxation. METHODS: In the
      first trial 200 ml and 500 ml meat soup (1 g fat/200 ml) was given to six healthy
      individuals. In the second trial a constant volume of soup (200 ml) containing
      graded amounts of fat (1, 10, and 20 g/200 ml) was given to seven healthy
      individuals. Gastric relaxation was investigated for 1 h after consumption of the
      soup. A sagittal cross-sectional antral was assessed ultrasonographically every
      10 min, and abdominal discomfort was scored. RESULTS: Overall, a positive
      response (volume increase of 30 ml or more within 5 min after consumption of the
      meal) was found in 26 of 30 (87%) investigations. Individual maximal responses
      ranged from 38 to 482 ml (mean, 180 ml +/- 128). Area under the time-volume curve
      (AUC) was similar after 200 and 500 ml soup (mean, 100 ml/30 min and 107 ml/30
      min, respectively). AUC increased with increasing fat content, with a significant
      difference between the low-fat and high-fat meal (p < 0.05). The barostat bag
      induced fed-state antral contractions in most individuals (p < 0.001). There was
      a negative correlation between AUC and postprandial abdominal discomfort (p =
      0.04). CONCLUSIONS: The barostat is a sensitive technique for detecting gastric
      relaxation, also in response to our standard meat soup meal. The postprandial
      relaxation response in healthy individuals in dependent on the fat content of the
      meal. The barostat bag may alter gastric motor activity. Abdominal discomfort
      after soup ingestion may be related to poor gastric relaxation.

PMID- 8578167
TI  - Gender and clinical presentation in adult celiac disease.
AB  - BACKGROUND: Celiac disease may present in various forms. This study aimed to
      investigate whether gender affects the clinical presentation of the disease in
      adult celiac patients from the Mediterranean area. METHODS: This study
      retrospectively analyzes data collected in all adult patients with celiac disease
      (n = 195) seen during the past 13 years at the Gastrointestinal Unit of the
      Federico II University of Naples, Italy. RESULTS: In these series of patients the
      ratio of women to men was 3.33. Age at diagnosis was lower in women that in men
      (p < 0.05). Except for asthenia, all signs and symptoms were more frequent in
      women than in men. Hypochromic anemia was the most commonest finding in women and
      was 40% more frequent in women than in men (p < 0.001). Dyspepsia was twice as
      frequent in women as in men (p < 0.05); genital disorders were reported by 44% of
      women and by no men. Recent weight loss or low body mass index was the commonest
      finding in men. About 60% of men and women reported diarrhea; among patients
      without diarrhea, the prevalence of hypochromic anemia differed between sexes (p
      < 0.05), occurring in about 80% of women. CONCLUSION: This study shows that the
      clinical presentation of celiac disease is not the same in men and women. The
      disease is not only more frequent in women than in men but is also more severe
      and more rapid. The data also suggest the need to look for celiac disease in
      patients with unexplained hypochromic anemia.

PMID- 8578168
TI  - Increased intestinal permeability for the isosmolar contrast medium iodixanol
      during small-bowel ischaemia in rats.
AB  - BACKGROUND: Intestinal ischaemia may be difficult to recognize in the early
      stages. Increased urinary recovery of water-soluble contrast medium during and
      intestinal follow-through has been suggested as a sign of bowel ischaemia.
      METHODS: Urinary excretion of the isosmolar water-soluble X-ray contrast medium
      iodixanol was measured after instillation via an orogastric tube in 56 rats with
      occlusion of the mesenteric blood vessels. RESULTS: Mesenteric venous occlusion
      caused only minor histologic alterations of the mucosa. High-performance liquid
      chromatography (HPLC) and X-ray fluorescence analysis measured urinary iodixanol
      concentrations 10 and 13 times higher than in the groups with mesenteric arterial
      occlusion than in controls (p < 0.001), and 3 and 4 times higher than in the
      group with venous occlusion (p < or = 0.05). Correlation between HPLC and X-ray
      fluorescence measurements of contrast medium in urine was strong (r = 0.98).
      CONCLUSION: Measuring urinary contrast medium levels during intestinal follow
      through may aid in distinguishing bowel ischaemia following mesenteric arterial
      occlusion from mesenteric venous occlusion and from the normal bowel.

PMID- 8578169
TI  - Anti-neutrophil serum attenuates dextran sulfate sodium-induced colonic damage in
      the rat.
AB  - BACKGROUND: The role of neutrophils in experimental colonic damage induced by
      dextran sulfate sodium is uncertain. We test the hypothesis that neutrophils are
      of pathogenic significance and anti-neutrophil serum will attenuate the colonic
      damage induced by oral dextran sulfate sodium in rats. METHODS: Rabbit anti-rat
      neutrophil serum (anti-neutrophil serum) or control rabbit serum was administered
      to, and circulating neutrophil count was monitored in, rats before and during
      feeding of dextran sulfate sodium or regular rat diet for 2 weeks. Histologic
      features of mucosal damage were evaluated in hematoxylin and eosin-stained
      proximal and distal colonic sections by a blinded observer. RESULTS: Oral dextran
      sulfate sodium induces weight loss, diarrhea, peripheral neutrophilia, and
      colonic damage. Anti-neutrophil serum induced neutropenia and significantly
      attenuated the weight loss, the neutrophil infiltration in the colon, and the
      mucosal necrosis and pathologic index in the distal colon. CONCLUSION: The data
      showing that anti-neutrophil serum attenuates distal colonic mucosal injury
      induced by dextran sulfate sodium support the hypothesis that neutrophils play a
      pathogenic role in this model of colonic mucosal damage.

PMID- 8578170
TI  - Differences in the intrinsic capacity of peripheral blood mononuclear cells to
      produce tumor necrosis factor alpha and beta in patients with inflammatory bowel
      disease and healthy controls.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF alpha) and beta (TNF beta) appear to
      play an important role in the regulation of the inflammatory response. The aim of
      the present study was to investigate the intrinsic capacity of peripheral blood
      mononuclear cells (PBMC) to produce these cytokines. METHODS: PBMC from 41
      patients with Crohn's disease (CD), with ulcerative colitis (UC), and 23 healthy
      controls (HC) were cultured for 48 h in the presence of the T-cell activators
      anti-CD3 and anti-CD28. Biologically active total TNF (TNF alpha and beta), TNF
      alpha, and TNF beta production were measured using a bioassay for biologically
      active TNF and specific TNF alpha and TNF beta enzyme-linked immunosorbent
      assays. RESULTS: Large interindividual differences in TNF production were
      observed. Production of biologically active TNF after T-cell stimulation was
      significantly decreased in UC patients as compared with HC and CD patients
      (median, 337 U/ml, 800 U/ml, and 1050 U/ml, respectively). Stimulated TNF alpha
      production in UC patients (median, 432 U/ml) and in CD patients (median, 537
      U/ml) did not differ statistically significantly from HC (median, 730 U/ml) as
      compared with HC and UC patients(median, 800 U/ml and 837 U/ml, respectively).
      CONCLUSIONS: These findings support the concept that UC and CD are homogeneous,
      clearly distinguishable disease entities but rather a heterogeneous group of
      diseases. Studies directed to assess the immunogenetic background of these
      different disease manifestations in IBD are underway.

PMID- 8578171
TI  - The fibrinolytic system in human ascites.
AB  - BACKGROUND: We recently reported that the contact and kallikrein-kinin systems
      are activated in malignancy-related ascites. We have now studied the fibrinolytic
      system in ascites and plasma from patients with gastrointestinal cancer(n = 14)
      and non-malignant liver disease (n = 18). METHODS AND RESULTS: Enzyme
      immunoassays (EIAs) showed that urokinase and tissue plasminogen activators (uPA,
      tPA) and PA inhibitors (PAI-1, PAI-2) were present in ascites from both patient
      groups and that tPA was the predominant PA. uPA, tPA, and PAI-1, were detected in
      plasma from patients and controls. These EIA findings were supported by
      zymography studies. Functional assays showed considerable generation of plasmin
      like activity and low plasminogen and antiplasmin values in malignancy-related
      ascites. The plasmin/antiplasmin and tPA/PAI-1 ratios were particularly high in
      malignancy-related ascites as compared with non-malignant ascites. Plasma from
      the liver disease patients showed a higher tPA/PAI-1 ratio and, thus a higher
      potential for plasminogen activation than plasma from cancer patients and
      controls. Patient plasma showed low values of plasmin-like activity, antiplasmin,
      and plasminogen. CONCLUSION: Our findings show that the fibrinolytic system is
      activated in malignancy-related ascites.

PMID- 8578172
TI  - Prognosis and life expectancy on alpha-1-antitrypsin deficiency and chronic liver
      disease.
AB  - BACKGROUND: Alpha-1-antitrypsin deficiency is a common autosomal recessive
      disorder associated with early development of emphysema, liver cirrhosis, and
      hepatocellular carcinoma. The aim of the present study was to define prognosis
      and life expectancy in patients with alpha 1-antitrypsin deficiency with and
      without chronic liver disease. METHODS: After a follow-up of 15 years the
      estimated life table analysis of mortality of 160 patients with alpha 1
      antitrypsin deficiency was retrospectively calculated. The survival time was
      estimated using the Kaplan-Meier survival curves and was compared with the life
      expectancy of the age- and sex-matched population of west Austria. RESULTS: Fifty
      four patients with alpha 1-antitrypsin patients had evidence of chronic liver
      disease; of these, 78% showed positive viral markers. Of the 106 patients with
      alpha 1-antitrypsin deficiency without chronic liver disease none had evidence of
      additional viral infection. Life expectancy in patients with alpha-1 antitrypsin
      deficiency and chronic liver disease was significantly lower than in patients
      with alpha 1-antitrypsin deficiency without chronic liver disease (p = 0.001). No
      difference in life expectancy in alpha 1-antitrypsin deficiency without chronic
      liver disease was found in comparison with that of the normal population.
      CONCLUSIONS: We suggest that in alpha 1-antitrypsin deficiency-associated chronic
      liver disease it is the high coinfection rather than the inborn error of
      metabolism itself that is responsible for a deterioration of life expectancy or
      for the poor prognosis of the disease.

PMID- 8578173
TI  - Chronic hepatitis C in alcoholic patients: prevalence, genotypes, and correlation
      to liver disease.
AB  - BACKGROUND: Only one-fifth of chronic alcoholic patients develop chronic liver
      disease in spite of continuous alcohol abuse. Hepatitis C has been proposed to be
      one of several suggested factors contributing to the development of liver
      disease. METHODS: In 201 consecutive chronic alcoholic patients admitted to the
      hospital for detoxification, antibodies to hepatitis C virus (HCV) were
      determined, using second-generation enzyme-linked immunosorbent assay (ELISA) and
      recombinant immunoblot assay (RIBA) tests. Sera from patients with antibodies
      were tested with polymerase chain reaction (PCR) to detect HCV RNA and
      subsequently genotyped. RESULTS: Twenty-nine patients (14%) were positive in the
      ELISA and RIBA tests. HCV RNA was detected in 23 of the 29 (79%); 21 could be
      genotyped. Previous intravenous drug abuse was present in 18 of 29 (58%) in the
      positive group versus 3 of 172 (2%) in the negative group (p < 0.001), whereas
      the prevalence of previous blood transfusions did not differ between the groups.
      In one-third of the positive cases no obvious route of transmission was found. On
      the basis of clinical and biochemical variables and, if available, histology,
      altogether 6 of 29 (21%) HCV-positive patients were classified as having severe
      liver disease as compared with 12 of 172 (7%) HCV-negative patients (p < 0.05).
      HCV-positive patients with liver disease were younger than HCV-negative patients
      with liver disease (p < 0.05). CONCLUSIONS: Hepatitis C virus infection is common
      among chronic alcoholic patients in Stockholm, especially among patients with a
      history of intravenous drug abuse. To confirm ongoing infection, detection of HCV
      RNA is necessary. This infection seems to be a factor contributing to the
      development of liver disease in alcoholic patients.

PMID- 8578174
TI  - Two dose regimens of recombinant interferon-alpha-2b in chronic hepatitis C virus
      infection. Biochemistry, hepatitis C virus RNA, and liver histology as response
      indices.
AB  - BACKGROUND: Recombinant interferon remains the cornerstone of treatment of
      chronic hepatitis C virus (HCV) infection. Still, evaluation of treatment on the
      basis of response indicators and long-term effect of the treatment raises several
      questions. METHODS: Seventy-four patients with chronic HCV infection were
      randomized to a high (3 MIU, 3/7 days) or low (1 MIU, 3/7 days) dose of
      recombinant interferon-alpha-2b for 48 weeks after a 4-week course of 3 MIU, 3/7
      days. Response to treatment was assessed by means of liver enzymes
      (transaminases), HCV RNA, and liver histology. RESULTS: The higher maintenance
      dose was associated with a significantly higher rate of sustained alanine
      aminotransferase (ALAT) response (45% versus 19%) and with a significantly better
      chance of becoming HCV RNA-negative during therapy (47% versus 23%). In the high
      maintenance dose group 14 of the 29 (48%) patients with available HCV RNA data
      were negative at the 3-month follow-up, compared with 4 of 27 (15%) in the low
      maintenance dose group. Significantly more patients had improved liver biopsy
      findings after interferon in the high maintenance dose group (79%) than in the
      low maintenance dose group (36%). There was a close correlation between ALAT
      response and HCV RNA response. Of 17 patients who were HCV RNA-negative 3 months
      after the end of treatment, 10 remained HCV RNA-negative 2-4 years later.
      CONCLUSION: The study demonstrates a higher response rate as assessed by
      biochemistry, HCV RNA, and liver histology in the higher dose group.

PMID- 8578175
TI  - Prevalence of gallstone disease in a Swedish population.
AB  - BACKGROUND: It has been claimed that the prevalence of gallstone disease (GD) is
      unusually high in Sweden. The prevalence is not known in either men or women.
      METHODS: An ultrasound technique was used in a population-based screening study
      to identify all subjects with GD and subjects with a history of cholecystectomy.
      Eight hundred 40- and 60-year-old men and women were asked to participate.
      RESULTS: Five hundred and fifty-six subjects were included, giving a response
      rate of 70%. The overall prevalence of GD was 15%. Women had a higher prevalence
      both at 40 and 60 years of age--11% and 25%, respectively--as compared with men,
      at 4% and 15%. Fifty per cent of subjects with GD had been cholecystectomized.
      CONCLUSIONS: Gallstone disease is common in Stockholm, and the prevalence is
      equal to that of other European cities where similar studies have been performed.
      Subjects with GD were more often cholecystectomized than in other parts of
      Europe.

PMID- 8578176
TI  - Antioxidant and calcium channel blockers counteract endothelial barrier injury
      induced by acute pancreatitis in rats.
AB  - BACKGROUND: Multiple organ failure is the major mortality-related complication in
      severe acute pancreatitis. Endothelial barrier injury may be involved in its
      pathophysiology. METHODS: The present study evaluated alterations in endothelial
      barrier integrity in different organs/tissues 12 h after induction of acute
      pancreatitis by intraductal infusions of bile. Potential effects of oxygen free
      radicals and calcium influx were evaluated by pretreatment with an antioxidant, N
      acetyl-L-cysteine, and calcium channel antagonists, verapamil and diltiazem.
      RESULTS: Tissue edema, reflected by an increase in tissue water content, was
      noted in the stomach, proximal small intestine, cecum, spleen, pancreas, kidneys,
      liver, lungs, heart, and brain in rats with pancreatitis. Also, an increased
      endothelial barrier permeability, as evidenced by the leakage of radiolabeled
      human serum albumin from blood to tissues, occurred in the stomach, proximal
      small intestine, colon, peritoneum, spleen, pancreas, kidneys, liver, lungs, and
      heart, accompanied by altered liver functions, increased levels of pancreatic
      enzymes, compromised renal function, and delayed intestinal motility. N-acetyl-L
      cysteine prevented tissue edema and endothelial permeability changes in most
      organs/tissues, whereas the effects of verapamil and diltiazem were less marked.
      The preventive effects occurred in an organ-dependent manner. CONCLUSIONS:
      Endothelial barrier injury is found in all investigated organs/tissues in acute
      experimental pancreatitis. Oxygen free radicals and calcium influx may play a
      role in the development of these changes.

PMID- 8578177
TI  - Detection of hepatic fibrogenesis: a review of available techniques.

PMID- 8578178
TI  - Dyspepsia in rural residents of Estonia. Life-style factors, psychoemotional
      disorders, and familial history of gastrointestinal diseases.
AB  - BACKGROUND: The association between dyspepsia and life-style factors,
      psychoemotional disorders, and familial history of gastrointestinal diseases was
      evaluated in a case-control study of dyspepsia. METHODS: A group of 500
      consecutive dyspeptic patients, attending a rural health care center, and a sex-
      and age-matched control group (n = 500) were interviewed using a specially
      compiled questionnaire. RESULTS: The dyspeptic subjects showed a significantly
      higher prevalence of psychoemotional disorders (p < 0.001), irregular dietary
      regimen (p < 0.05), and familial history of gastrointestinal diseases. The number
      of ex-smokers was also larger in dyspeptic subjects (p < 0.05). CONCLUSIONS: Our
      study showed that the subject group with the heterogeneous syndrome of dyspepsia
      has several characteristics in common.

PMID- 8578179
TI  - Are frequent short gastro-oesophageal reflux episodes the cause of symptoms in
      patients with non-ulcer dyspepsia responding to treatment with ranitidine?
AB  - BACKGROUND: Patients with non-ulcer dyspepsia (NUD) responding to treatment with
      H2-receptor antagonists have no clinically useful characteristics. This trial
      compares the gastro-oesophageal reflux pattern as measured by 24-h oesophageal pH
      monitoring in patients responding to ranitidine with that of non-responders.
      METHODS: Thirty-one patients with NUD were randomized to 6 weeks' double-blind
      alternating treatment with 150 mg ranitidine twice daily or placebo and
      classified as responders or non-responders. RESULTS: Pathologic gastro
      oesophageal reflux was seen in 3 of the 13 responders and 4 of the 18 no
      responders (NS). The responders had frequent short reflux episodes (< 1 min in
      duration). When 4 patients with > or = 5 reflux episodes longer than 5 min were
      excluded, the number of short reflux episodes (median) in responders and non
      responders was 32 and 14, respectively. The difference is statistically
      significant (p = 0.025). There were no other differences between the groups.
      CONCLUSIONS: In this study patients with NUD responding to ranitidine were
      characterized by frequent short reflux episodes in the absence of numerous long
      reflux episodes.

PMID- 8578180
TI  - Esophageal motility disorders and their coexistence with pathologic acid reflux
      in patients with noncardiac chest pain.
AB  - BACKGROUND: The aim of this study was to determine which motility data of
      patients with noncardiac chest pain (NCCP) differ from those of controls on the
      basis of long-term manometry and to evaluate the coexistence of motility
      disorders and pathologic acid reflux. Further, motility disorders were tested as
      to whether they were secondary to acid reflux. METHODS: Combined long-term
      pH/manometry was performed in 95 patients with NCCP, using one pH-electrode and
      two pressure transducers. The motility data were compared with those of healthy
      controls (n = 40). In addition, an intraindividual patient-oriented motility
      analysis was performed. Evaluated were the amplitude, the duration in the distal
      and proximal esophagus, and the type of propagation, propulsive and simultaneous,
      of esophageal contractions. Ten patients with pathologic acid reflux and
      hypermotility disorders received 20 mg omeprazole twice daily and were
      investigated again 4 weeks after therapy began. RESULTS: The median distal
      pressure amplitude (39.4 versus 28.9 mmHg, p < 0.0001) and the median percentage
      of simultaneous contractions (18.5% versus 10%; p < 0.0001) were significantly
      higher in patients with NCCP than in controls. In addition, patients whose
      symptoms correlated with abnormal motility (n = 18) had a significantly higher
      median duration of contractions (3.8 sec versus 3.2 sec; p < 0.03) than controls
      Patients with pathologic acid reflux showed a higher median distal pressure
      amplitude (38.3 mmHg versus 28.9 mmHg; p < 0.0001) and median percentage of
      simultaneous contractions (18% versus 10%; p < 0.0001) than controls.
      Furthermore, a high rate of coexistence with hypermotility disorders was observed
      (64%). These disorders persisted after acid suppression therapy. CONCLUSIONS:
      Patients with NCCP differ from controls in their esophageal motility.
      Simultaneous contractions of increased amplitude and duration are pathologic. The
      intraindividual patient-oriented motility analysis is an appropriate evaluation
      method. Hypermotility disorders occur often in patients with pathologic acid
      reflux, but apparently they are not dependent on it.

PMID- 8578181
TI  - Omeprazole in the long-term treatment of gastro-oesophageal reflux disease. A
      double-blind randomized dose-finding study.
AB  - BACKGROUND: Omeprazole is effective in the treatment of reflux oesophagitis, and
      it is important to determine the lower dose limit with still appropriate clinical
      efficacy. METHODS: Patients with endoscopic oesophagitis grade 1-4 (N = 220) were
      randomized to double-blind treatment with 20 mg or 40 mg omeprazole daily for 4-8
      weeks. Those healed after this initial treatment phase were re-randomized to
      double-blind treatment with 20 mg omeprazole daily (n = 67), 10 mg omeprazole
      daily (n = 68), or placebo (n = 33) for 6 months. Remission was defined as the
      absence of any endoscopic sign of oesophagitis. RESULTS: Healing rates were
      increased with 40 mg omeprazole, the therapeutic gain compared with the 20-mg
      dose being 15% after 4 and 8 weeks. The proportion of patients in remission after
      6 months was 59% with 20 mg omeprazole, 35% with 10 mg omeprazole, and 0% with
      placebo. CONCLUSION: Maintenance treatment with 10 mg omeprazole can prevent
      recurrence of oesophagitis in about one-third of patients with all grades of
      oesophagitis, and 20 mg omeprazole in about twice as many.

PMID- 8578182
TI  - Distribution of extracellular matrix proteins in indomethacin-induced lesions in
      the rat stomach.
AB  - INTRODUCTION: We investigated the distribution of extracellular matrix (ECM)
      proteins in indomethacin-induced lesions of the rat stomach. METHOD: Twenty rats
      received indomethacin orally at a dose of 8 mg/kg/body weight. The animals were
      killed at 3, 6, 12, 24, and 48 h after administration of the drug. The stomachs
      were removed and frozen in liquid nitrogen. Cryostat serial sections of the
      lesions were immunostained with antibodies to collagen III, IV, and VI, laminin,
      and fibronectin. RESULTS: Fibronectin was the dominant extracellular protein of
      the provisional ECM in deep gastric lesions and gastric ulcers. Collagen III was
      strongly positive in stromal cells under the necrotic material in gastric
      erosions. Basal membrane proteins (collagen IV and laminin) were found to
      originate from the muscularis mucosae at the ulcer edge. CONCLUSION: There is a
      typical distribution of ECM proteins in erosions and ulcers of the rat stomach.
      Fibronectin was most prominent in the provisional matrix of gastric erosions and
      ulcers.

PMID- 8578183
TI  - Antioxidants inhibit ethanol-induced gastric injury in the rat. Role of
      manganese, glycine, and carotene.
AB  - BACKGROUND: Oxygen-derived radicals are implicated in the pathogenesis of tissue
      damage and ulcerogenesis. This study aimed to examine the effect of manganese,
      glycine, and carotene, oxygen radical scavengers, on ethanol-induced gastric
      lesions in the rat and on ethanol cytotoxicity in epithelial cell culture.
      METHODS: MnCl2 + glycine (12.5-50 mg/rat) were injected subcutaneously up to 6 h
      before oral administration of 1 ml of 96% ethanol, and 0.5 ml carrot juice or
      beta-carotene was given orally 30 min before the ethanol. Mucosal injury was
      evaluated 1 h later by gross and microscopic scoring. The effect of Mn2+ and
      carrot juice was also tested in monolayers of radiolabeled epithelial cells
      exposed to H2O2 + ethanol injury as expressed by the extent of the isotope
      leakage. RESULTS: Mn2+ and glycine pretreatment dose-dependently reduced ethanol
      induced gastric lesion formation. Protection was maximal when treatment was
      applied 4 h before the insult. Gross damage was also markedly prevented by
      pretreatment with carotenes and dimethylthiourea (DMTU, 75 mg/kg
      intraperitoneally) but not by allopurinol. Mixtures of subtoxic concentrations of
      ethanol and H2O2 were highly lethal for epithelial cell monolayers. In this
      model, cell death was markedly attenuated by catalase, DMTU, Mn2+, and carrot
      juice. CONCLUSIONS: Ethanol-induced gastric mucosal damage may involve generation
      of oxygen-derived radicals, independent of the xanthine oxidase system. By acting
      as oxygen radical scavengers, Mn2+, glycine, and carotenes, like catalase and
      DMTU, provide significant gastroprotection.

PMID- 8578184
TI  - The pH/PCO2 method for continuous determination of human gastric acid and
      bicarbonate secretion. A validation study.
AB  - BACKGROUND: The present paper describes and evaluates a methodologic approach for
      registration of the fast, interdigestive, motility-related changes in gastric
      acid and bicarbonate outputs seen in man. METHODS: The technique is based on
      continuous gastric luminal perfusion and measurements of pH and PCO2 in gastric
      effluent and concomitant intragastric/duodenal manometry. Fourteen healthy
      volunteers participated. RESULTS: Direct acid secretory estimations from pH
      recordings, corrected for hydrogen ion activity, correlated closely with values
      obtained by conventional titration. After intragastric infusion of bicarbonate,
      96 +/- 5% of the newly measured steady-state value was registered virtually
      instantaneously provided that corrections for the PCO2 electrode time constant
      and the perfusion/aspiration time were made. In the neutral pH range (pH 5-7),
      practically full quantitative recovery of intragastrically infused bicarbonate
      was obtained. In the acid pH interval (pH 2-5) the recovery was significantly
      lower (53 +/- 6%; p < 0.01). With an aspirate without air admixture and during
      high perfusion rates (31 and 46 ml/min), full recovery of bicarbonate was
      obtained also at an acid pH, whereas a reduced perfusion rate (16 ml/min)
      significantly (p < 0.05) reduced the recovery rate. CONCLUSIONS: With the pH/PCO2
      technique both acid and bicarbonate assessments have a close to on-line time
      resolution. Acid output is measured accurately, but the method potentially
      underestimates actual bicarbonate levels in the acid pH range, a combined effect
      of diffusion of CO2 into air bubbles in the aspirate and into the gastric mucosa
      from the lumen. A high gastric perfusion rate minimizes this source of error. The
      pH/PCO2 technique is well suited for studies of the interaction between secretion
      and motility in the human stomach.

PMID- 8578185
TI  - Non-bleeding visible vessel treatment: perendoscopic injection therapy versus
      omeprazole infusion.
AB  - BACKGROUND: The non-bleeding visible vessel in a peptic ulcer is the highest risk
      factor for a bleeding recurrence among not actively bleeding lesions.
      Perendoscopic injection of sclerosing compounds is usually used as prophylaxis
      against rebleeding. METHODS: Forty-two patients with visible vessels in a peptic
      ulcer at an emergency endoscopic procedure have been studied: 21 patients
      underwent prophylactic perendoscopic hemostasis, and 21 patients were infused
      with omeprazole intravenously. RESULTS: Eight patients (19%), four in each group,
      had early rebleedings (within 48 h after the enrollment). There was no
      significant difference between the two types of treatment. At the endoscopic
      control after 48 h there were significantly more lesions with higher risk of
      rebleeding (Forrest IIa and IIb) in the group treated with perendoscopic
      hemostasis. CONCLUSIONS: Our data suggest that omeprazole infusion is a valid
      alternative to injection treatment of non-bleeding visible vessels.

PMID- 8578186
TI  - Helicobacter pylori infection in Finnish children and adolescents. A serologic
      cross-sectional and follow-up study.
AB  - BACKGROUND: The purpose was to examine the epidemiology of Helicobacter pylori
      infection in Finnish children and adolescents. METHODS: Blood samples taken from
      healthy subjects (n = 461) 3-18 years old were studied cross-sectionally for the
      presence of H. pylori antibodies. Additionally, blood samples drawn in 1980,
      1983, 1986, and 1989 from 74 children born in 1977 were tested. Serum IgG-class
      antibodies to H. pylori were determined by an enzyme immunoassay. RESULTS: In the
      cross-sectional series the mean antibody levels and the percentage of
      seropositive children increased with age. The overall seroprevalence was 10.2%.
      During the follow-up period from 3 to 12 years of age the seropositivity
      increased from 4.6% to 5.7%. On the basis of the seroconversions between 3 and 12
      years of age the annual incidence of H. pylori infection was calculated to be
      only 0.3%. CONCLUSIONS: In children seropositivity for H. pylori of the IgG class
      is often a sign of an infection acquired in early childhood. It seems likely that
      the age-dependent increase in the seropositivity reflects cumulation of a chronic
      infection.

PMID- 8578187
TI  - Inhibitory effect of dopamine on gastric motility in rats.
AB  - BACKGROUND: There is disagreement with regard to the involvement of dopamine (DA)
      receptors in gastric motility. The mechanisms of the inhibitory effect of DA on
      rat gastric motility was investigated in association with acetylcholine (Ach)
      release in the present study. METHODS: In vivo vagotomized, splanchnicectomized
      rats and control rats were used, and gastric movement was determined as the
      gastric motility index after DA administration. In vitro study of Ach release
      from the circular muscle strips of the gastric corpus was investigated after
      administration of domperidone, SCH23390, phentolamine, or propranolol. RESULTS:
      In the in vivo study DA inhibited gastric motility in a dose-dependent manner.
      Vagotomy and splanchnicectomy had no effect on the inhibitory effect of DA. In
      vitro study DA inhibited [3H]-Ach release in a dose-dependent manner. The
      inhibitory effect of DA was antagonized by domperidone but not by phentolamine,
      propranolol, or SCH23390. CONCLUSIONS: Inhibition of gastric motility by dopamine
      is independent of extrinsic innervation and seems to be mediated by DA2 receptors
      in the gastric wall.

PMID- 8578188
TI  - 51Cr-labelled ethylenediaminetetraacetic acid and D-xylose absorption test in
      Escherichia coli enterotoxin-induced diarrhoea in mice.
AB  - BACKGROUND AND METHODS: D-Xylose and 51Cr-labelled ethylenediaminetetraacetic
      acid (EDTA) absorption tests were evaluated in control and Escherichia coli heat
      stable, heat-labile, and both heat-stable and heat-labile enterotoxin-induced
      diarrhoea in mice. RESULTS: The absorption of D-xylose was greatest 45 min after
      its ingestion in both control and enterotoxin-treated groups. There was a
      significant (p < 0.01) decrease in xylose absorption at 45 min in all the three
      experimental groups as compared with the control group, which may be due to
      change in membrane fluidity and hence change in membrane permeability, whereas
      51Cr-EDTA absorption was at its maximum 15 min after its ingestion in both
      control and experimental groups. And there was a significant (p < 0.05) increase
      in 51Cr-EDTA absorption in enterotoxin-treated groups as compared with the
      control group. CONCLUSIONS: These results suggest a change in tight junctional
      permeability which may be due to change in the cytoskeletal microfilaments. Both
      these tests hence show that E. coli enterotoxin-induced diarrhoea results in
      absorption and permeability changes.

PMID- 8578189
TI  - Glucagon-like peptide 1 (7-36 amide) secretion in response to luminal sucrose
      from the upper and lower gut. A study using alpha-glucosidase inhibition
      (acarbose).
AB  - BACKGROUND: After nutrient ingestion there is an early response of glucagon-like
      peptide 1 (GLP-1) immunoreactivity, although GLP-1 is mainly produced in
      endocrine cells from the lower gut (ileum and colon/rectum), suggesting that
      indirect stimulation is important after the ingestion of carbohydrates that are
      predominantly absorbed from the upper intestine. METHODS: To enable contact of
      sucrose with lower gut mucosa, sucrose was administered by mouth with and without
      the simultaneous ingestion of 100 mg of the alpha-glucosidase inhibitor acarbose
      to six normal healthy volunteers. RESULTS: There was an early increment in GLP-1
      15 min after sucrose ingestion. With acarbose, sucrose reached the colon
      approximately 120 min after ingestion, as indicated by an increment in breath
      hydrogen exhalation (p < 0.0001), and GLP-1 release was prolonged (p < 0.0001).
      The sucrose-related increments in glucose, insulin, C-peptide, and gastric
      inhibitory polypeptide (GIP) and the suppression of glucagon were only marginally
      affected by acarbose administration. CONCLUSIONS: GLP-1 release appears to be
      influenced by indirect mechanisms (early response after sucrose) and by direct
      luminal contact with lower gut mucosal endocrine cells (late response with
      acarbose).

PMID- 8578190
TI  - Colonic fermentation of complex dietary carbohydrates in short-bowel patients. No
      association with hydrogen excretion and fecal and plasma short-chain fatty acids.
AB  - BACKGROUND: The colonic degradation of carbohydrates (fermentation) to short
      chain fatty acids (SCFAs) appears to have major impacts on colonocyte function,
      sodium and water absorption, and large-bowel energy salvation, but how to
      quantify the in vivo fermentation in man is still debatable. METHODS: Indicators
      of colonic fermentation, fecal and plasma SCFAs and breath hydrogen (H2), were
      measured in 10 short-bowel patients (mean +/- SE; 106 +/- 21 cm) with totally
      preserved large bowels who were on a 60% high-carbohydrate, 20% low-fat diet,
      compared with the reversed isocaloric 20% low-carbohydrate, 60% high-fat diet.
      This human model showed large differences in large-bowel fermentation, as
      excretions of calories were reduced (40%; 485 +/- 151 kcal/day) and excretions of
      carbohydrates were unchanged and low with the high-carbohydrate diet as compared
      with the low-carbohydrate diet, in contrast to unchanged calorie excretion in
      short-bowel patients with no colonic function. RESULTS: Fecal concentrations of
      SCFAs did not change when the diet was changed from the high content to the low
      content of carbohydrates (82 +/- 11 mmol/l and 79 +/- 9 mmol/l, respectively).
      The ratio of acetate in feces increased (from 48 +/- 4% to 54 +/- 3%; p = 0.01)
      on the high-carbohydrate diet, whereas the percentage of the other SCFAs
      decreased proportionally. Plasma SCFAs 2 h and 6 h after breakfast were also
      identical when comparing the two dietary regimens. Nor were the peak H2 breath
      excretion and the area under the H2 excretion-versus-time curve increased by the
      threefold increase in the intake of dietary carbohydrates. CONCLUSIONS: Fecal and
      plasma SCFAs and breath H2 excretion are of limited value in the evaluation of
      even large differences in colonic fermentation of complex dietary carbohydrates.

PMID- 8578191
TI  - Histologic detection of trophozoites of Giardia lamblia in the terminal ileum.
AB  - BACKGROUND: The occurrence of trophozoites of Giardia lamblia in mucosal biopsy
      specimens obtained from the terminal ileum and associated histologic changes are
      reported. METHODS: In this retrospective histologic analysis an average of 3.2
      (range, 1-7) Giardia-positive biopsy specimens obtained from the terminal ileum
      of 32 subjects was examined. Colonization was defined as sparse (1-10
      trophozoites per specimen), intermediate (10-30 trophozoites per specimen), or
      heavy (more than 30 trophozoites). The number of intraepithelial lymphocytes
      (IEL) was assessed and the results expressed as the number of IEL/100 epithelial
      cells. Grade of villous flattening was determined semiquantitatively. The number
      of lymphoid follicles per biopsy specimen was counted, and the degree of mucosal
      inflammation determined semiquantitatively. Ileal mucosa biopsy specimens from 32
      Giardia-free cases, classified histologically as normal, served as control.
      RESULTS: Twelve of the patients were female, and twenty male. The mean age was 46
      years (range, 20-68 years). Light colonization with G. lamblia was observed in 13
      (40.6%) patients, intermediate in 6 (18.8%), and heavy colonization in 13 (40.6%;
      range, 2-215 trophozoites/case). Normal villous architecture was seen in all
      cases. The numbers of lymphocytes and granulocytes in the lamina propria were
      considered to be within the normal range in all patients with giardiasis and in
      all controls. The occurrence of lymphoid follicles and the content in IEL did not
      differ significantly in Giardia-positive and -negative cases. CONCLUSIONS: G.
      lamblia can colonize the terminal ileum and may therefore be detected in biopsy
      specimens obtained from this area. Owing to the absence of associated histologic
      changes a search for the parasites themselves has to be made in the specimen.

PMID- 8578192
TI  - Blastocystis hominis in human immunodeficiency virus-related diarrhea.
AB  - BACKGROUND: A wide variety of bacterial, viral, and parasitic pathogens can cause
      severe diarrhea in patients with advanced human immunodeficiency virus (HIV)
      infection. Conflicting evidence exists as to whether Blastocystis hominis should
      also be included among the infectious agents capable of causing HIV-related
      diarrhea. METHODS: We determined the prevalence and clinical significance of B.
      hominis in a cohort of 262 patients with HIV infection, presenting at the
      infectious diseases department of a tertiary referral university hospital in
      northern Germany. RESULTS: B. hominis was detected in stool samples of 99
      patients (38%). The isolation rate varied highly between the different groups.
      Homosexual men (43%; odds ratio (OR), 2.1; p = 0.01) had a higher detection rate
      than patients from other risk groups (26%), and patients with acquired
      immunodeficiency syndrome (46%; OR, 1.8; p = 0.03) were more likely to carry B.
      hominis than patients in earlier stages of their HIV infection (32%). An
      association with clinical symptoms was not evident. Presence of B. hominis,
      however, was frequently associated with the concurrent isolation of other enteric
      pathogens or apathogenic parasites. CONCLUSIONS: The data suggest that the
      isolation of B. hominis does not justify treatment even in symptomatic, severely
      immunocompromised patients. Most patients will either have spontaneous resolution
      of symptoms or successful identification of other infectious or noninfectious
      etiologies. Therapy should be limited to patients with persistent unexplained
      symptoms after a thorough evaluation and a complete screening for alternative
      etiologies, including the use of endoscopic procedures and the careful
      examination of multiple specimens.

PMID- 8578193
TI  - Adhesion molecule expression on vascular endothelium and nitroblue tetrazolium
      reducing activity in human colonic mucosa.
AB  - BACKGROUND: Expression of adhesion molecules is increased in inflamed colonic
      mucosa, but little is known about their functional activity in vascular
      endothelium. METHODS: We studied in situ nitroblue tetrazolium reducing activity
      and expression of E-selectin, ICAM-1, CD31, and VCAM-1 by immunohistochemistry in
      the same biopsy specimen in controls and patients with ulcerative colitis (UC).
      RESULTS: VCAM-1 expression was negative in mucosal vessels. E-selectin-positive
      vessels were significantly increased in endoscopically active colitis compared
      with normal mucosa. ICAM-1-positive vessels were consistently found in normal,
      quiescent UC and active UC. CD31-positive vessels were not significantly
      increased in quiescent UC and active UC compared with control. Only E-selectin
      significantly correlated with the histologic grade of inflammation. Nitroblue
      tetrazolium reducing vessels were increased in inflamed mucosa, and these vessels
      expressed ICAM-1 and CD31. E-selectin positivity in association with nitroblue
      tetrazolium reduction was mainly seen in the large mucosal vessels, but
      capillaries showing nitroblue tetrazolium reduction were rarely positive for E
      selectin. CONCLUSIONS: Phenotypic and functional activation of vascular
      endothelium might be involved in the recruitment of leukocytes and tissue
      destruction of inflamed colonic mucosa.

PMID- 8578194
TI  - Somatostatin attenuates the hyperdynamic circulatory state in the gastric mucosa
      of rats with portal hypertension.
AB  - BACKGROUND: Portal hypertensive gastropathy is characterized by a hyperdynamic
      circulatory state in the gastric mucosa. We assessed the effect of bolus
      injection of somatostatin on gastric mucosal perfusion in a rat model of portal
      hypertension. We tested the hypothesis that somatostatin will reduce gastric
      mucosal perfusion in portal hypertension. METHODS: Portal hypertension was
      induced by two-stage portal vein ligation (PVL). Two weeks after PVL significant
      elevation of portal venous pressure was demonstrated. Gastric mucosal hemodynamic
      changes were measured by reflectance spectrophotometry, which records the indexes
      of mucosal hemoglobin oxygen saturation (ISO2) and mucosal hemoglobin
      concentration (IHB). RESULTS: After an intravenous bolus of 1 microgram
      somatostatin significant reductions of ISO2 and IHB were demonstrated in the rats
      with PVL (ISO2, -34 +/- 5%; IHB, -15 +/- 2%) and the controls (ISO2, -26 +/- 4%;
      IHB, -15 +/- 2%). A dose-response relationship was shown by using 0.01, 0.1, and
      1 microgram of somatostatin. Somatostatin did not induce other hemodynamic
      changes except a transient drop in systemic blood pressure of 8-10%. CONCLUSION:
      The significant reductions of gastric mucosal ISO2 and IHB by somatostatin
      support the hypothesis that somatostatin is capable of attenuating the
      hyperdynamic circulatory state in the gastric mucosa of rats with portal
      hypertension and may have a beneficial effect on portal hypertensive gastropathy.
      This hypothesis deserves to be evaluated in clinical studies.

PMID- 8578195
TI  - Cerebral edema due to hemodialysis in paracetamol-induced fulminant hepatic
      failure.

PMID- 8578196
TI  - Current Perspectives and Future Practice in Gastrointestinal Disease. Proceedings
      and abstracts of the 7th International Sucralfate Symposium. Santa Barbara,
      California, September 1994.

PMID- 8578197
TI  - To repair the fault or end the acid reign?
AB  - BACKGROUND: Despite the vast effort and expense devoted to the elucidation of the
      cause of esophagogastro-duodenal ulcer disease, relatively minimal progress has
      been made towards the understanding of causation. Since earliest times, it has
      been recognized that milk, chalk powder, or charcoal ameliorate the disease
      process and its symptoms. In addition, the avoidance of acidic or spicy foods
      provides some relief. Thus ulcer disease has been ascribed to acid or the
      consequences of hyperacidity. Reams of data and countless meetings have purported
      to confirm and support this viewpoint. Surprisingly, the co-secretion in the
      stomach of the powerful proteolytic enzyme pepsin has been virtually ignored as a
      pathogenetic agent. Marshalling distant antipodean resources, a novel bacteria,
      H. pylori, was identified as a significant causative agent in ulcer disease. To
      the amazement of nobody but gastroenterologists, it became apparent that there
      might be more than one cause for ulcer disease. Subsequently, both corporations
      and physicians seized the reins of multi-variant antibiotic therapy as a panacea
      for the third millennium treatment of peptic ulcer disease. Only a brave few have
      raised the issues of possible abnormalities in intrinsic mucosal function which
      might generate a locus minoris resistentiae. Defective mucosal repair mechanisms
      have barely been evaluated, since the regulation of normal mucosal healing is so
      poorly understood. Nevertheless, consideration of the therapeutic potential of
      mucosal protection has found support at both an intellectual and a clinical
      level. The more exciting recent possibility of the local delivery of growth
      factors which might promote healing has provided a unique opportunity for further
      therapeutic advance. CONCLUSIONS: Indeed in the future the exogenous regulation
      of mucosal repair may provide a milieu conductive to the resolution of an old but
      ill-understood problem. It is certainly apparent that processes beyond parietal
      cell proton secretion are critical and require both delineation and management.
      The acid reign may be in decline but the site of the fault and its repair remain
      to be defined.

PMID- 8578198
TI  - Growth factors: new 'endogenous drugs' for ulcer healing.
AB  - BACKGROUND: The pathogenesis of gastroduodenal ulceration has been investigated
      mostly from the point of view of aggressive factors; the therapeutic
      interventions affected the healing process only indirectly. With the discovery of
      the potent healing capacity of growth factors, direct treatment of ulcers is now
      possible regardless of HCl and pepsin secretion. We review our recent data on how
      growth factors (e.g., bFGF, PDGF in comparison with EGF) can promote ulcer
      healing. RESULTS: Treatment of rats with bFGF, PDGF accelerated the healing of
      experimental chronic duodenal and gastric ulcers without suppressing gastric acid
      secretion and resulted in superior quality of ulcers healed. We also detected
      additive or synergistic action between bFGF and cimetidine or bFGF and sucralfate
      in the healing of chemically induced chronic duodenal ulcers and chronic erosive
      gastritis. CONCLUSIONS: We conclude that growth factors such as bFGF, PDGF can
      promote ulcer healing without the need to neutralize gastric secretion and may
      lead to a direct and efficient therapeutic regime.

PMID- 8578199
TI  - Stimulation of mucosal glutathione and angiogenesis: new mechanisms of
      gastroprotection and ulcer healing by sucralfate.
AB  - BACKGROUND: Among the endogenous mediators (e.g., PG, SH) of gastroprotection, so
      far only PG was implicated in the mechanism of acute gastroprotection by
      sucralfate. Angiogenesis, which is stimulated by bFGF, is a recently recognized
      element in ulcer healing, and sucralfate binds bFGF in vitro and in vivo.
      METHODS: In fasted rats the gastric mucosal concentration of GSH and protein SH
      was measured at 30, 60, 120, and 240 min after a single gastroprotective dose of
      sucralfate. In normally fed rats, angiogenesis was measured in the subcutaneous
      sponge assay 7 days after the implantation of sponges containing sucralfate
      and/or bFGF. RESULTS: A gastroprotective dose of sucralfate time-dependently
      increased GSH concentration in the gastric mucosa. Sucralfate alone accelerated
      angiogenesis, which was significantly enhanced by combination with an ineffective
      dose of bFGF in the subcutaneous sponge assay. The same dose of sucralfate
      combined with an angiogenic dose of bFGF also resulted in synergistic stimulation
      (e.g., more than fivefold) of angiogenesis. CONCLUSIONS: It appears that elevated
      mucosal GSH concentration may represent a new factor in the mechanism of acute
      gastroprotection by sucralfate, and stimulation of angiogenesis is one of the
      mechanisms of ulcer healing by sucralfate.

PMID- 8578200
TI  - Nitric oxide in gastroprotective and ulcer healing effects of sucralfate.
AB  - BACKGROUND: Sucralfate is known to protect gastric mucosa against the damaging
      action of strong irritants and to accelerate healing of chronic ulcers, but the
      mechanisms underlying these effects have not been elucidated. Similar
      gastroprotective and healing effects can be obtained with exogenous donors of
      nitric oxide (NO) and prostaglandins (PG). METHODS: The area of gastric lesions
      was measured by planimetry. Gastric blood flow was determined using laser Doppler
      flowmetry. The role of NO in the prevention of ethanol-induced gastric damage and
      in the healing of gastric ulcerations by sucralfate and nocloprost, a stable PGE2
      analog, was therefore assessed. RESULTS: Pretreatment with NG-nitro-L-arginine (L
      NNA), an inhibitor of NO synthase, enhanced ethanol-induced mucosal damage and
      reduced dose-dependently the gastroprotective and hyperemic effects of
      sucralfate. The doses of L-NNA attenuating significantly the protective effects
      of sucralfate were 25-50 mg/kg. The effects of L-NNA were reversed by the
      addition of L-arginine but not D-arginine. For comparison, the gastroprotective
      (but not hyperemic) effects of nocloprost were not affected by the pretreatment
      with L-NNA and/or arginine. Daily treatment with L-NNA (50 mg/kg per day)
      prolonged the healing of chronic gastric ulcers and significantly reduced the
      acceleration of healing by sucralfate. CONCLUSIONS: We conclude that (i) the
      gastroprotective and hyperemic effects of sucralfate involve, at least in part,
      the NO-arginine pathway, (ii) the ulcer healing effects of sucralfate may also
      involve NO, probably through the hyperemia around the ulcer, and (iii) NO is not
      essential for the mucosal protection of PGE2 analog, but may account for the
      gastric vasodilatory effect of this PG.

PMID- 8578201
TI  - Critical reappraisal of mucosal repair mechanisms.
AB  - The repair of the mucosal surface of the stomach is a complex process involving a
      number of different cell systems. These include mucosal enterocytes, matrix
      proteins, and cells responsible for angiogenesis. The regulation of each of these
      systems is as yet poorly defined and the interaction between the different
      components remains to be characterized. The signal system involved in recognition
      of damage initiates a cascade of events which broadly comprise cell migration,
      cell proliferation, lineage determination, matrix reconfiguration, and
      angiogenesis. Critical regulators of this process include the trefoil peptides,
      specific adhesion molecules, and the modulators of cell lineage. The utility of
      specific pharmacotherapeutic probes, whether responsible for surface protection,
      growth factor delivery, acid inhibition, or growth factor amplification, remains
      to be rigorously defined. The repair of the mucosal defect is critical in
      establishing the functional integrity of the gastric luminal surface. In order to
      facilitate rapid and long-lasting repair of mucosal injury, a precise
      understanding of the specific biological events participant in the repair process
      is required. At this time, there is only a paucity of such information available.

PMID- 8578202
TI  - Dyspepsia update.
AB  - BACKGROUND: Non-Ulcer Dyspepsia (NUD) is a very common problem which has many
      causes. Trying to group dyspeptic patients according to symptoms has been
      proposed in order to improve our understanding of the problem and to aid both
      clinical trials and indeed practice by studying and treating homogeneous groups.
      REVIEW: The literature has been reviewed to see if sub-groups of dyspepsia are
      standing up to scrutiny and clinically relevant. RESULTS: Reflux-like dyspepsia
      may now be identified accurately in a high proportion by a combination of careful
      history and the use of intra-oesophageal 24-h pH monitoring. Acid suppressing
      therapy is often useful in this group. Dysmotility-like dyspepsia is currently an
      area of active investigation with growing evidence that there is abnormal gastric
      emptying. Response to pro-kinetic drugs looks encouraging. Ulcer-like dyspepsia:
      Appears to be the largest dyspeptic group. Acid secretion is normal. Helicobacter
      pylori does not correlate with any group of dyspepsia. CONCLUSION: Separating NUD
      into groups is becoming useful in both investigation and treatment, but more
      specific simple tests are needed to take this further.

PMID- 8578203
TI  - Reflux esophagitis: overview.
AB  - Reflux eosophagitis is one of the most common chronic disorders in humans. While
      ultimately due to contact of esophageal epithelium with gastric acid and pepsin,
      the pathogenesis of the condition remains poorly understood. In the present
      manuscript, some key clinical aspects of this condition are briefly reviewed,
      including pathogenesis, complications, diagnosis, and treatment.

PMID- 8578204
TI  - Quality of life and cost of therapy in reflux disease.
AB  - BACKGROUND AND RESULTS IN THE LITERATURE: Reflux symptoms are common, with an
      incidence of up to 40% monthly and 7% daily in the general adult population. The
      duration of symptoms in patients seeking help for reflux is often in excess of 5
      years in an unselected population. A majority, 70%, of those with daily symptoms
      do not have esophagitis at endoscopy but still require regular medication for
      symptom control. After treatment, relapse is seen in a majority of cases in whom
      esophagitis is present at start of therapy. Symptoms of reflux and upper
      abdominal dyspepsia affect several aspects of daily living. Consequently quality
      of life (QoL) is low in patients with reflux esophagitis and upper dyspepsia.
      Values normalize during medical treatment or after surgery for reflux
      esophagitis. Cost of treatment is complex. Evaluations in patients with reflux
      esophagitis are based on the effectiveness and cost of the drug, the cost of
      investigations and time lost from work. In comparisons based on the results of
      clinical healing trials, omeprazole has been found the most cost-effective drug
      for treatment of reflux esophagitis. There are as yet no evaluations made for
      patients with reflux symptoms only. CONCLUSIONS: The consequences for the patient
      and society regarding QoL and costs for reflux symptoms should be evaluated more
      closely to optimize future therapy.

PMID- 8578205
TI  - Dyspepsia and esophageal reflux: an overview.
AB  - BACKGROUND: Dyspepsia is a major problem in the community with considerable
      morbidity. RESULTS: Appropriate therapy improves the quality of life of such
      patients and emphasizes the important role of diagnosis and management. The role
      of Helicobacter pylori is still to be defined, as does measurement of
      dysmotility. The management of reflux-like dyspepsia, in particular, assumes
      increasing importance in terms of cost-benefit.

PMID- 8578206
TI  - Sucralfate: prophylaxis of mucosal damage during cancer therapy.
AB  - BACKGROUND: Chemotherapy and radiotherapy of different malignancies may be
      complicated by a variety of side effects, some of which may be related mucosal
      damage. RESULTS: There is increasing evidence that sucralfate reduces the
      severity of radiation-induced mucositis in the head and neck, esophagus, and the
      lower gastrointestinal tract. Sucralfate also seems to protect the skin during
      radiotherapy and to reduce chemotherapy-induced mucositis. CONCLUSION: Further
      studies could be of interest to define the clinical significance of sucralfate in
      reducing the mucosal damage and increasing quality of life during an following
      cancer therapy.

PMID- 8578207
TI  - Stress ulcer prophylaxis: gastrointestinal bleeding and nosocomial pneumonia.
      Best evidence synthesis.
AB  - PURPOSE: To examine the effect of stress ulcer prophylaxis on gastrointestinal
      bleeding, pneumonia, and mortality. METHODS: Computerized search of published and
      unpublished research, bibliographies, pharmaceutical and personal files and
      abstract reports. Independent review of 257 articles identified 71 relevant
      randomized trials for inclusion. We made independent, duplicate assessment of the
      methodologic quality, population, intervention and outcomes of each trial.
      RESULTS: This overview demonstrates that prophylaxis with histamine-2-receptor
      antagonists decreases the incidence of overt gastrointestinal bleeding (odds
      ratio 0.29 [95% CI 0.17-0.45]) and clinically important bleeding (odds ratio 0.35
      [95% CI 0.15-0.76]). There is a trend to decreased overt bleeding when antacids
      are compared with no therapy (odds ratio 0.35 [95% CI 0.08-1.33]). Although
      sucralfate, antacids, and histamine-2-receptor antagonists are equivalent in
      reducing clinically important bleeding, sucralfate decreases the incidence of
      nosocomial pneumonia compared with antacids and/or histamine-2-receptor
      antagonists (odds ratio 0.50 [95% CI 0.21-0.79]). Sucralfate is associated with
      lower mortality relative to antacids (odds ratio 0.70 [95% CI 0.52-0.94]), and
      relative to histamine-2-receptor antagonists (odds ratio 0.71 [95% CI 0.49
      1.04]). CONCLUSIONS: All stress ulcer prophylactic agents appear to be effective
      in decreasing bleeding. Prophylaxis with sucralfate is associated with a lower
      rate of nosocomial pneumonia and mortality, providing strong evidence for use of
      this agent in clinical practice.

PMID- 8578208
TI  - Gastric alkalinization, pneumonia, and systemic infections: the controversy.
AB  - BACKGROUND: Gastric alkalinization has been suspected as a cause of pneumonia in
      critically ill patients. Although meta-analysis of the available data confirms an
      association between the administration of antacids/H2-antagonists and the risk of
      pneumonia, controversy remains whether stress ulcer prophylaxis with sucralfate
      reduces the risk of pneumonia. We hypothesized that the conflicting study results
      may be due to differences in patient population and general treatment regimens.
      RISK FACTORS: Microbiological studies have shown that a gastric pH > 4 is crucial
      for overgrowth of gastric gram-negative but not gram-positive bacteria.
      Sucralfate mainly influences the growth of gram-negative bacteria. Thus, in
      patient groups with a high frequency of gram-positive pneumonia, preservation of
      gastric acidity does not influence the pneumonia rate. Since 40-60% of critically
      ill patients show gastric pH values > 4 even without administration of acid
      neutralizing agents, an increased risk of nosocomial pneumonia with antacids/H2
      antagonists can only be expected if these agents substantially increase the
      frequency of patients with gastric pH > 4. No influence of stress ulcer
      prophylaxis on the pneumonia rate can be expected in patients on enteral
      nutrition, especially if administered continuously. In non-ventilated patients or
      in those with a short duration of ventilation no significant influence of stress
      ulcer prophylaxis on nosocomial pneumonia rate can be expected. The same is true
      for patient groups where regurgitation of gastric content is prevented, e.g. head
      up position in neurosurgical patients. Furthermore, in patient groups with
      primary lung injury nosocomial pneumonia occurs due to specific pathomechanisms,
      e.g. lung contusion or inhalation injury. Based on these factors we have
      developed a scoring system and have performed a regression analysis between the
      sum of the risk scores and the odds ratio of nosocomial pneumonia of all
      available stress ulcer studies dealing with nosocomial pneumonia. RESULTS: A
      highly significant correlation (p < 0.0001) could be demonstrated between the sum
      of the risk score and the odds ratio for pneumonia. An increased risk of
      nosocomial pneumonia due to stress ulcer prophylaxis with antacids/H2-antagonists
      occurred in patient groups with a risk score of > or = 2. CONCLUSIONS: This
      analysis supports the hypothesis that gastric alkalinization significantly
      increases the risk of nosocomial pneumonia in long-term ventilated patients.
      However, this analysis also shows that only specific subgroups of patients
      benefit from acid-independent stress ulcer prophylaxis relative to nosocomial
      pneumonia. Furthermore, recent experimental and clinical studies support the
      hypothesis that gastric alkalinization may increase the risk of systemic
      infections and that sucralfate may have significant protective effects.

PMID- 8578209
TI  - Rapid epithelial restitution in the stomach: an updated perspective.
AB  - BACKGROUND: Rapid epithelial restitution (RER) of rodent and amphibian gastric
      mucosa was described in the early 1980s. It begins within minutes of superficial
      injury and is accomplished by migrating interfoveolar and mucous neck cells.
      METHODS: Subsequent studies using electrophysiologic and morphologic techniques
      have shown additional aspects of RER. RESULTS: (i) Cells migrating at later times
      (> 4 h) are not phenotypically mucous cells but undifferentiated cells,
      suggesting that two cell types cover mucosal defects. (ii) One of the factors
      necessary for optimal RER is an intact basal lamina. Superficial gastric
      epithelial cells preferentially adhere and spread on basal lamina substrates in
      the following order: Matrigel > collagen IV > fibronectin > laminin. (iii) RER
      can be accelerated in vitro in amphibian gastric mucosa by the addition of basic
      fibroblast growth factor or sucrose octasulfate. (iv) Cells with microwounds in
      the plasma membrane can still migrate as part of RER. CONCLUSION: Despite these
      additional data on RER it is still uncertain whether its acceleration can prevent
      gastric ulceration or if its impairment leads to gastric ulceration.

PMID- 8578210
TI  - Long-term strategies for peptic ulcer.
AB  - Commonly when treatment is stopped most peptic ulcers recur. The prevention of
      ulcer recurrence by continuous long-term therapy, usually with H2-receptor
      antagonists, provides effective and convenient management in patients at risk in
      order to reduce the chance of relapse, complications, and associated mortality.
      High relapse rates of peptic ulcer suggest the need for continuous H2-antagonists
      in elderly patients, those receiving NSAID, aspirin or anticoagulants, those with
      coexistent medical conditions and those with previous haemorrhage or perforation.
      Patients suitable for intermittent therapy include those who are < 60 years, with
      no previous ulcer complications, no coexistent medical conditions and few
      recurrences. Long-term H2-antagonists have an enviable safety profile and are
      cost effective. Despite this, the possibility of permanent cure of peptic ulcer
      by Helicobacter pylori eradication suggests that long-term therapy may not be
      needed. We face the exciting prospect of placing peptic ulcer into the annals of
      history.

PMID- 8578211
TI  - Helicobacter pylori in ulcerogenesis.
AB  - Patients with peptic ulcer disease have elevated gastric acid secretion,
      hyperfunction of G cell, impaired bicarbonate secretion, increased levels of
      pepsinogen I and the presence of inflammatory mediators as well as Helicobacter
      pylori-induced gastroduodenitis and gastric metaplasia in the duodenum (in
      duodenal ulcer patients). Non-H. pylori-associated ulcers include those due to
      non-steroidal anti-inflammatory drugs, Zollinger-Ellison syndrome, and those
      related to other forms of gastritis. Evidence of H. pylori in ulcerogenesis
      includes the higher prevalence of H. pylori in gastritis and peptic ulcer
      patients plus the important observation that H. pylori eradication results in
      healing and long-term cure of ulcer disease. The precise mechanism of mucosal
      injury and ulceration is unclear. Bacterial and inflammatory factors are involved
      as well as host changes in hormones and gastric acid secretion.

PMID- 8578212
TI  - Peptic ulcer and Helicobacter pylori: eradication and relapse.
AB  - BACKGROUND: All duodenal ulcers and the vast majority of gastric ulcers are the
      consequence of Helicobacter pylori-associated inflammation. In duodenal ulcer
      disease, the inflammation is maximally intense in the antrum and is associated
      with gastric metaplasia in the bulb. H. pylori is presumably more virulent in
      duodenal ulcer disease. Gastrin homeostasis is disturbed and there is robust acid
      secretion. In gastric ulcers, there is pangastritis with a degree of atrophy.
      Acid secretion is normal or low. METHODS: Analysis of the literature data is
      performed concerning ulcer relapse rates after cure of the infection. RESULTS:
      Successful eradication of the infection cures both the duodenal ulcer and gastric
      ulcer diathesis. Amalgamated figures for ulcer relapse/year in H. pylori +ve
      duodenal ulcer is 58% compared to 2.6% for H. pylori -ve duodenal ulcer patients.
      The corresponding figures for gastric ulcers are > 50% for H. pylori +ve and 2.0%
      for H. pylori -ve patients. Many of the recurrent ulcers in H. pylori -ve
      patients occurred in individuals consuming aspirin or NSAID. This striking
      difference persists over at least 7 years, as the reinfection rate in the
      developed world is < 1%/year. Moreover, recurrent bleeding in bleeding-prone
      duodenal ulcer patients is abolished after cure of the infection. CONCLUSION: The
      decreased relapse rate after cure of the infection is the most compelling
      argument in favour of the infectious etiology of peptic ulcer disease.

PMID- 8578213
TI  - Helicobacter pylori eradication: a critical appraisal and current concerns.
AB  - Helicobacter pylori is now well recognized as a critical factor in the majority
      of patients with peptic ulcer disease and successful treatment of the infection
      results in cure of the disease. However, treatment of this infection has proved
      difficult, involving a combination of drugs, and has usually involved complex
      treatment regimens. Triple therapy involving a bismuth compound in combination
      with metronidazole and tetracycline or amoxicillin have been most widely used and
      achieve successful cure of the infection in about 90% of cases when the
      tetracycline combination is used. More recently, the use of the proton-pump
      inhibitors in combination with amoxicillin have been widely advocated to combine
      effective symptom relief with high ulcer healing rates and an opportunity to cure
      the disease. However, all these treatments have some disadvantages due to
      unpredictability, adverse events, complex regimens making compliance difficult,
      or cost. This article reviews the results of current treatments for the
      eradication of H. pylori infection and identifies opportunities for the
      development of optimal approaches to the cure of this infection.

PMID- 8578214
TI  - Sucralfate counteracts the inhibition of gastric mucosal mucin receptor by
      Helicobacter pylori lipopolysaccharide.
AB  - BACKGROUND: Among the disturbances in gastric mucosal defense associated with
      Helicobacter pylori infection is the loss of mucus coat continuity, which results
      in a severe disturbance in the ability of mucus coat to maintain its functions as
      the pre-epithelial element of gastric mucosal defense. Here, we show that H.
      pylori, through its cell-wall lipopolysaccharide, disrupts the interaction
      between gastric mucin and its mucosal receptor, and that sucralfate is capable of
      counteracting this untoward effect of the bacterium. METHODS: The receptor was
      isolated from octylglucoside-solubilized gastric mucosal epithelial cell
      membranes by affinity chromatography on Sepharose-bound wheat germ agglutinin and
      following iodination with 125I, used in the binding assays for mucin in the
      presence of H. pylori lipopolysaccharide and sucralfate. RESULTS: Preincubation
      of the receptor protein with H. pylori lipopolysaccharide led to a decrease in
      mucin binding. The inhibitory effect was proportional to the concentration of
      lipopolysaccharide and reached a maximum of 91% at 30 micrograms/ml. The effect
      of H. pylori lipopolysaccharide was countered by sucralfate, which caused a dose
      dependent relief of the inhibitory effect. The maximum (75%) restoration in mucin
      receptor binding occurred at 60 micrograms/ml sucralfate. CONCLUSIONS: The
      results provide strong evidence for the effectiveness of sucralfate in preventing
      the loss of gastric mucus coat continuity caused by H. pylori.

PMID- 8578215
TI  - Sucralfate affects the susceptibility of Helicobacter pylori to antimicrobial
      agents.
AB  - BACKGROUND: Infection with Helicobacter pylori is regarded as a primary factor in
      the pathogenesis of gastric disease, and successful therapies now include a
      combination of antiulcer drugs with antimicrobial agents. In this study, we
      investigated the effect of sucralfate and omeprazole on the vitro anti-H. pylori
      activity of metronidazole, erythromycin, tetracycline, and amoxycillin. METHODS:
      Aliquots of H. pylori culture were transferred to the wells containing different
      concentrations of antibiotics either alone or in the presence of various doses of
      sucralfate and omeprazole and incubated for 3 days for MIC evaluation. RESULTS:
      The assays in the absence of sucralfate and omeprazole gave MIC value 0.10 mg/l
      for erythromycin, 0.12 mg/l for amoxycillin, 0.15 mg/l for tetracycline, and 14
      mg/l for metronidazole. Inclusion of sucralfate evoked a 28% enhancement in the
      MIC of metronidazole, 2.5-fold in tetracycline, 8-fold in erythromycin, and 2
      fold in amoxycillin. In the presence of omeprazole, the MIC of erythromycin
      improved 4-fold, tetracycline 1.6-fold, and amoxycillin, 2-fold. CONCLUSIONS: The
      results demonstrate that sucralfate enhances the anti-H. pylori activity of
      antibiotics and that this effect is comparable to that of omeprazole.

PMID- 8578216
TI  - Effect of sucralfate on Helicobacter pylori and severity of gastritis in patients
      with duodenal ulcer.
AB  - BACKGROUND: Duodenal ulcer relapse rates have been reported to be lower following
      healing with sucralfate. The question arises whether this is related to an effect
      on Helicobacter pylori. METHODS: In order to investigate this possibility, 43
      patients with active duodenal ulcer were entered into a study. Endoscopy was
      performed at entry, following 6 weeks' treatment with sucralfate 1 g q.i.d., and
      at 4 and 12 weeks of post-documented healing. Antral and gastric corpus biopsies
      were taken for assessment of H. pylori status (CLOtest), density of infection,
      and severity of gastritis. In addition, 14C urea breath tests (UBT) were
      performed. RESULTS: Sucralfate therapy induced a significant decrease in the
      density of H. pylori infection, with a trend to improvement of the gastritis in
      the antrum, but not in the corpus. However, all patients remained CLOtest
      positive, and the overall gastric urease activity was unchanged following
      therapy. These effects did not appear to influence either initial duodenal ulcer
      healing or subsequent relapse rates. CONCLUSION: Sucralfate has a suppressive
      effect on H. pylori infection in the gastric antrum but the clinical relevance of
      this is uncertain.

PMID- 8578217
TI  - Sucralfate in Helicobacter pylori eradication strategies.
AB  - BACKGROUND: Sucralfate monotherapy has been shown to suppress but not eradicate
      Helicobacter pylori. The combination of sucralfate with antibiotic(s) has been
      evaluated recently in the treatment of H. pylori-positive duodenal ulcer. The aim
      of this article is to review the efficacy of sucralfate-containing duotherapy and
      triple therapy in duodenal ulcer healing and H. pylori eradication rates.
      METHODS: Reports on duotherapy and triple therapy including sucralfate as the
      mediating agent were analysed to assess the duodenal ulcer healing and H. pylori
      eradication rates. RESULTS: One study on duotherapy with sucralfate and
      amoxycillin achieved an ulcer healing rate of 86% and H. pylori eradication rate
      of 40%, which compared favourably with sucralfate monotherapy that resulted in
      duodenal ulcer healing and H. pylori eradication rates of 65% and 0%
      respectively. A total of six studies have examined triple therapy using
      sucralfate with two antibiotics. The duodenal ulcer healing rates were generally
      over 90% and the H. pylori eradication rates about 80% (range 59% to 100%). In
      one comparative study, the 4-week duodenal ulcer healing and H. pylori
      eradication rates of sucralfate-containing triple therapy were not
      distinguishable from those of omeprazole-containing triple therapy. CONCLUSIONS:
      It is concluded that sucralfate is an effective mediating agent for the
      eradication of H. pylori in patients with duodenal ulcer.

PMID- 8578218
TI  - Cellular and molecular mechanisms of gastric ulcer healing. Is the quality of
      mucosal scar affected by treatment?
AB  - BACKGROUND: Ulcer healing, i.e. the reconstruction of the mucosal architecture,
      is an active process of filling the mucosal defect with proliferating and
      migrating epithelial cells and connective tissue. METHODS: This article
      represents a summary of histologic and ultrastructural assessment of the cellular
      events occurring during healing of experimental gastric ulcer. RESULTS: Mucosa
      adjacent to the ulcer crater forms a 'healing' zone. The gastric glands in this
      zone dilate and the epithelial cells lining these glands de-differentiate,
      express epidermal growth factor receptor, and proliferate. The latter is the
      result of local activation of genes encoding for EGF and its receptors. At the
      ulcer margin, proliferating and dividing epithelial cells migrate onto the
      granulation tissue to cover (re-epithelialize) the ulcer and bud into granulation
      tissue to reconstruct glandular structures within the ulcer scar. Re
      epithelialization and reconstruction of epithelial structures is under control of
      epidermal growth factor (EGF) and related peptides which are produced locally by
      regenerating cells. Under control of fibroblast growth factors, granulation
      connective tissue grows extensively supplying (a) microvessels for restoration of
      the microvascular network and (b) connective tissue cells for restoration of the
      lamina propria within the mucosal scar. The final outcome of the healing process
      reflects a dynamic interaction between the epithelial component for the 'healing'
      zone at the ulcer margin and the connective tissue component (including
      microvessels) originating from the granulation tissue. Depending on these
      interactions, mucosal scar can be of good quality (restoration close to normal)
      or poor quality. While a number of pharmacologic agents affect gastric ulcer
      healing, it is unknown whether these drugs affect the quality of mucosal
      architecture reconstruction. In previous studies, we demonstrated that sucralfate
      exerts a trophic effect on gastric mucosa and, compared with omeprazole, improves
      the quality of restored mucosal structures within the scar of healed gastric
      ulcers. In the most recent studies, we demonstrated that treatment with
      sucralfate activates genes for EGF, bFGF, and their receptors, significantly
      increasing (vs placebo and omeprazole) expression of EGF and its receptor in
      ulcerated gastric mucosa. CONCLUSION: Thus, the superior quality of ulcer healing
      by sucralfate (versus omeprazole) is most likely based on its capacity to induce
      and stimulate expression of EGF, bFGF, and their receptors.

PMID- 8578220
TI  - 9th Highlights of Gastroenterology in The Netherlands. Proceedings of a
      symposium. Rome, Italy, 14-17 April 1994.

PMID- 8578219
TI  - Helicobacter pylori and peptic ulcer.
AB  - Helicobacter pylori is an important pathogen causing both gastric and duodenal
      ulcer. The causal relationship is based on the strong association of peptic ulcer
      with H. pylori-induced gastritis, the improved rate of healing with H. pylori
      suppression, and markedly low recurrence rates for ulcer after H. pylori
      eradication. The ideal regimen for H. pylori eradication should be simple,
      inexpensive, free of side effects, and effective in at least 90% of patients.
      Triple therapy involving bismuth, metronidazole and tetracycline or amoxicillin
      results in the best and most consistent eradication data, but there is a
      significant incidence of side effects and problems with compliance. Acid
      suppression with ranitidine or omeprazole combined with antibiotics is effective
      but expensive with variable results in clinical trials. Sucralfate may also
      reduce H. pylori density and enhance the action of antibiotics used in
      eradication regimens. Studies reported in this Journal suggest that sucralfate
      can be successfully substituted for bismuth in triple therapy regimens with
      documented efficacy and few side effects. Considerable progress in developing
      newer regimens to eradicate H. pylori has been made. However, the development of
      an ideal drug or regimen remains a challenge.

PMID- 8578221
TI  - New developments in antiviral therapy for chronic hepatitis B infection.
AB  - The standard treatment of an HBeAg-positive, HBV-DNA-positive chronic hepatitis B
      patient is a 16-week course of 10 MU alpha-interferon thrice weekly. However, the
      overall therapeutic effect, as measured by disappearance of the HBe-antigen, is
      estimated at 30%. Improvement is possible by better selection of the patient,
      modifications in the treatment schedule, or combination therapy. In the selection
      of possible candidates for combination therapy, the second generation nucleoside
      analogues with activity against hepatitis B are good candidates. In clinical
      studies, lamivudine and famciclovir are used, both of which can reduce serum HBV
      DNA to levels below 1 pg/ml within weeks. The ongoing clinical studies address
      the efficacy and safety of these drugs after prolonged exposure, in combination
      with alpha-interferon and around liver transplantation in patients with
      decompensated liver disease.

PMID- 8578222
TI  - NSAID-associated upper gastrointestinal damage in patients with rheumatoid
      arthritis.
AB  - AIM OF THE STUDY: The main aim of the present study was to identify the patient
      with rheumatoid arthritis (RA) taking non-steroidal anti-inflammatory drugs
      (NSAIDs) at risk for peptic ulcer disease (PUD) and its life-threatening
      complications. PATIENTS AND METHODS: During a retrospective study in which more
      than 1000 patients were interviewed, current gastrointestinal (GI) complaints
      were of no use in detecting current PUD. RESULTS: A history of PUD was an
      important predictor of current PUD, while the predictive value of serologic
      parameters, such as serum values of pepsinogen and antibodies to Helicobacter
      pylori, was disappointingly low. A prospective study in which 81 consecutive RA
      patients underwent a gastroscopy revealed 16% PUD; again a history of PUD was the
      most important predictive parameter. Since no study had been undertaken into the
      effects of a NSAID on intragastric pH we performed such a study, the main
      conclusion being that indomethacin does not influence the intragastric pH of RA
      patients. A placebo-controlled study of ranitidine 300 mg b.i.d. for the
      prevention of recurrent PUD in RA patients on NSAIDs is underway.

PMID- 8578223
TI  - Role of extended lymph node dissection in the treatment of gastrointestinal
      tumours: a review of the literature.
AB  - Over recent decades the long-term survival of patients operated on for
      gastrointestinal cancer has shown little if any improvement, despite sometimes
      aggressive surgical procedures and a significant fall in postoperative mortality.
      BACKGROUND: We went through the literature to see if there were any eventual
      effects of extended lymph node dissection or survival. METHODOLOGY: We reviewed
      recent literature on the different types of gastrointestinal cancer. RESULTS:
      Japanese centres report excellent results when wide local excision is combined
      ith systematic extended lymph node dissection, especially in gastric and
      oseophageal cancer. The overall 5-year survival of over 50% for the large number
      of patients undergoing gastric resection for cancer seems to demonstrate
      convincingly the value of the extended lymphadenectomy. All oriental studies are
      uncontrolled, as are most reports from Western countries. The role of extended
      lymphadenectomy is therefore far from certain. The results from two randomized
      studies (British Medical Research Council and Dutch Gastric Cancer Trial) are
      awaited. It is evident from these prospective studies that the procedure adds a
      considerable operative risk. From non-randomized studies there is evidence that
      extended lymph node dissection in the treatment of pancreatic cancer might be of
      benefit to patients with small stage I and II tumours. In the treatment of
      proximal bile duct cancer the main goal of surgery is optimal relief of biliary
      obstruction. Whether there will ever be a role for extensive lymphadenectomy is
      doubtful. The extent of the surgical procedure in the treatment of gallbladder
      cancer is related to the depth of tumour infiltration. Extended resections are
      only recommended for patients with stage II to IV tumours. Extended lateral
      pelvic node dissection in the treatment of rectal cancer is demonstrated in
      Japanese retrospective studies to induce considerable urogenital problems,
      whereas the risk for local recurrence is still present. CONCLUSIONS: No firm
      conclusions can be drawn based on data as available from the studied literature.
      Trial results will have to be awaited. Specific subgroups such as gastric and
      rectal cancer might benefit from these more extensive procedures.

PMID- 8578224
TI  - Pain in chronic pancreatitis.
AB  - Pain in chronic pancreatitis is usually so intense and long-lasting that follow
      up care of patients is often difficult and frustrating. Many therapeutical
      options to relieve pain have been recommended, but controlled studies are
      limited. The approach to patients with chronic pancreatitis complicated by pain
      is dependent on several factors. Medical therapy is initially attempted, but a
      switch to drainage procedure shortly thereafter in patients with persistent
      pseudocysts or a dilated pancreatic duct. Lithotripsy and endoscopic removal of
      pancreatic duct concrements may reduce pain in selected patients with a limited
      number of stones and strictures. In many patients, however, a drainage procedure
      cannot be offered and advantages and disadvantages of a resection or denervation
      procedure should be weighed against long-term treatment with analgetics.
      Resections should be limited to the most affected part of the pancreas. Usually
      this concerns the head. In such cases, a Whipple resection is often carried out,
      but duodenum-preserving procedures may offer several advantages.

PMID- 8578225
TI  - H2-receptor antagonists an Helicobacter pylori eradication.
AB  - BACKGROUND: To discuss the place of histamine H2-receptor antagonists in
      eradication therapy of Helicobacter pylori. METHODS: Analysis of two papers in
      this supplement and the relevant literature. RESULTS: Triple therapy comprising
      ranitidine and two antibiotics is effective in speeding up healing of duodenal
      ulcer and eradicating H. pylori from the stomach. CONCLUSION: Ranitidine is to be
      considered as a valuable and safe component of triple therapy against H. pylori
      in duodenal ulcer patients.

PMID- 8578227
TI  - Hepatitis B-associated liver cirrhosis as an indication for liver
      transplantation.
AB  - Fourteen HBsAg-positive patients received a liver transplant in Groningen. Two
      were HBeAg-positive and 12 HBeAg-negative. No anti-HBs immunoglobulin was given
      at the time. Both HBeAg-positive and 9 of 12 of the HBeAg-negative patients
      became HBsAg-positive again after transplantation. Virus titers were tested in
      eight patients. Two HBeAg-negative patients were HBV-DNA-negative at
      transplantation and are still HBV-DNA-negative one-and-half-years after
      transplantation, both by the branched DNA hybridization technique and by PCR (cut
      off values 0.7 x 10(6) and 10(3) HBV genomes/ml, respectively). One patient who
      had a low HBV-DNA titer at transplantation remained PCR-positive thereafter, but
      became HBsAg-negative. All other patients were HBV-DNA-positive and had a
      recurrence that rapidly led to high HBV titers. The liver histology was
      characterized by fibrosis and cirrhosis, centrilobular cholestasis and high
      expression of HBsAg and HBcAg, but with little inflammatory infiltrate. We
      conclude from these results that without anti-HBs immunoglobulin prophylaxis
      there is a high rate of HBV recurrence after transplantation. The current policy
      is that patients who test negative in the HBV-DNA dot-blot assay (< 10(7)
      genomes/ml) are transplantation candidates and are treated with high-dose anti
      HBs immunoglobulin after transplantation. HBV-DNA-positive patients (> 10(7)
      genomes/ml) remain poor candidates for liver transplantation, even with anti-HBs
      immunoprophylaxis.

PMID- 8578226
TI  - Bacteria in the aetio-pathogenesis of gastric cancer: a review.
AB  - Severe atrophic gastritis, a precursor lesion of gastric carcinoma, is connected,
      in two different ways, with intragastric bacterial colonization: (1) in advanced
      atrophic body gastritis (type A), achlorhydria or severe hypochlorhydria leads to
      bacterial overgrowth with aerobic and anaerobic flora enabling the conversion of
      nitrate to nitrite and further to N-nitroso compounds; (2) the newly re
      discovered Helicobacter pylori is probably one of the major causes of chronic
      atrophic antral gastritis (type B). Both types of bacteria may be involved in the
      pathogenesis of multifocal gastritis (type AB). In the western world,
      achlorhydric atrophic gastritis is not only found in pernicious anaemia but is
      latent in about 2 to 6% of the general population. In one study from the Mayo
      Clinic, about one-third of consecutive gastric carcinomas were present in
      achlorhydric stomachs, the remainder in acid-secretors. Apart from the N-nitroso
      compounds, other carcinogenic mechanisms may be active in type A gastritis:
      elevated serum gastrin; altered cell turnover; immunologic and hereditary traits.
      The association of H. pylori with gastric carcinoma is mainly based on
      circumstantial evidence: (i) epidemiological studies indicate a moderately
      increased risk for gastric cancer in H. pylori-positive subjects compared with H.
      pylori-negative; (ii) in the presence of H. pylori intragastric levels of the
      anti-oxidant ascorbic acid are lowered; (iii) H. pylori seems to be linked to
      mucosal atrophy and intestinal metaplasia; (iv) recent follow-up studies show a
      significant development of atrophic gastritis in H. pylori-positive patients
      compared to H. pylori-negative.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8578229
TI  - Clinical and physiological aspects of ileal pouch-anal anastomosis.
AB  - Proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of
      choice for severe chronic ulcerative colitis and familial polyposis coli because
      the entire colonic mucosa is removed while anal function can be preserved and the
      necessity for permanent ileostomy is eliminated. Long-term functional results are
      generally gratifying, as defecation frequency and degree of incontinence are
      acceptable in most patients. Pouchitis, however, a non-specific inflammation of
      the ileal reservoir, is a major long-term complication occurring in a
      considerable number of patients. The etiology of pouchitis is unknown. Since
      pouchitis occurs more frequently or even exclusively in ulcerative colitis
      patients it is assumed that pouchitis is a novel manifestation of inflammatory
      bowel disease. However, bacterial overgrowth in the ileal pouch may also play a
      pathogenetic role. Chronic inflammation and villous atrophy of varying severity
      is found in virtually all pouches. Acute inflammatory changes and ulceration are
      associated with pouchitis.

PMID- 8578228
TI  - Intestinal T lymphocytes.
AB  - The intestine is largely colonized by bacteria and further exposed to an immense
      array of ingested and shed immunogenic material. Therefore, the gut associated
      lymphoid tissue plays a major role in the human immune system. It may even
      constitute a unique immune system of its own, since it has been demonstrated to
      differ anatomically, phenotypically, functionally and on a molecular basis from
      its systemic counterpart and other peripheral lymphoid tissue. This is ultimately
      reflected by the observation in (transgenic) mice that intraepithelial T cells
      can develop independently of the thymus. Along the same lines, a rapidly growing
      body of evidences suggests that human bone marrow precursors can home to the gut
      epithelium, rearrange their T cell receptor genes and further differentiate in
      the mucosal micro environment. This, and other features that characterize the
      'diffuse' mucosal T cell infiltrate will be discussed.

PMID- 8578230
TI  - Triple therapy with ranitidine, clarithromycin, and metronidazole in the
      treatment of Helicobacter pylori.
AB  - BACKGROUND: To determine whether a triple therapy regimen for the treatment of
      Helicobacter pylori infection, consisting of ranitidine 300 mg q.i.d.,
      clarithromycin 500 mg t.i.d., and metronidazole 500 mg t.i.d. would provide a
      safe and effective treatment regimen, we performed an open prospective study in
      20 consecutive patients with proven H. pylori-associated non-ulcer dyspepsia or
      peptic ulcer disease. METHODS: The percentage of patients in whom eradication of
      H. pylori succeeded was determined. A semiquantitative assessment of histology
      was performed, and the results were analysed using Wilcoxon's matched-pairs ranks
      tests; side effects were noted and graded. RESULTS: Eradication was achieved in
      19 of 20 patients, i.e. in 95% (confidence interval 85-100%). Eradication of the
      bacterium led to a significant improvement in semiquantitative histology scores;
      active antral inflammation decreased from (mean +/- SEM) 1.84 +/- 0.19 to 0.21 +/
      0.16 (p = 0.0004) and chronic antral inflammation from 2.47 +/- 0.14 to 1.16 +/-
      0.14 (p = 0.0002); active gastric body inflammation decreased from 0.95 +/- 0.19
      to 0.00 +/- 0.00 (p = 0.0015) and chronic inflammation from 1.68 +/- 0.17 to 0.32
      +/- 0.11 (p = 0.0007). Side effects occurred in 45% of patients, but in over half
      of these patients only mild side effects occurred. Severe side effects did not
      occur, none of the patients discontinued the triple therapy. CONCLUSIONS: Triple
      therapy with ranitidine, clarithromycin, and metronidazole provides a safe and
      effective treatment of H. pylori infection, resulting in a high eradication rate,
      and in significant decrease in semiquantitative histology scores. Further
      prospective studies are warranted.

PMID- 8578231
TI  - Changing patterns in the treatment of carcinoma of the esophagus.
AB  - BACKGROUND: Decision-making in esophageal carcinoma. Treatment of carcinoma of
      the esophagus knows a great variety of modalities, ranging from simple palliative
      endoscopic pertubation to extensive curative operations. METHODS: Retrospective
      review. RESULTS: The three main groups of tumors are squamous cell carcinoma
      related to alcohol and tobacco abuse; adenocarcinoma in Barrett's esophagus
      related to long-standing gastroesophageal reflux; and adenocarcinoma of the
      cardia the origin of which is still unknown. Dysphagia and retrosternal pain are
      not only the most important symptoms but also the most important factors
      regarding survival. Diagnosis is made by endoscopy and biopsy. In the
      pretreatment staging a careful selection of the great variety of available
      diagnostic tools should be made. The ever-increasing diversity of local
      palliative procedures: tubing, photoablation, brachytherapy all have their place,
      but should not be allowed to distract us from the fact that surgery is the only
      hope for cure in these patients. Surgery should only be performed with curative
      intent and even then the long-term results are modest, with a 5-year survival of
      about 40% in node-negative and 18% in node-positive patients. CONCLUSION: In
      patients with carcinoma of the esophagus a polydisciplinary treatment approach is
      mandatory.

PMID- 8578232
TI  - 'The tropics in our bathroom': chronic diarrhoea after return from the tropics.
AB  - Interest in imported tropical diseases has increased with the rising number of
      travellers to the tropics. This is especially true in the case of tropical
      gastroenterologic disorders. The causative organisms of chronic diarrhoea are
      different from those causing acute diarrhoea. Bacteria are relatively unusual;
      parasites, e.g. Entamoeba histolytica or Giardia lamblia or an opportunistic
      parasitic infestation associated with an HIV infection are more likely.
      Furthermore, non-infectious causes, such as postinfective tropical malabsorption,
      lactase deficiency or coeliac disease have to be considered. Today, elderly
      people often undertake a journey to the tropics; in these cases the diarrhoea may
      be associated not only with an increased susceptibility to tropical bowel
      infections but also with causes previously present, such as diverticulosis,
      carcinoma or inflammatory bowel disease. The classification of chronic diarrhoea
      following a visit to the tropics is essentially the same as that for acute
      diarrhoea: diarrhoea with and without fever and with and without blood. In
      addition, malabsorption is an important feature of chronic diarrhoea.

PMID- 8578233
TI  - Helicobacter pylori eradication: unravelling the facts.
AB  - BACKGROUND: Recommendations for the choice, doses or duration of eradication
      therapy are still lacking. The purpose of this review was therefore to assess
      what conclusions could be drawn about eradication therapy, subsequent reinfection
      with Helicobacter pylori and ulcer recurrence. METHODS: Data were extracted from
      published papers and abstracts and entered into a dedicated database for
      appropriate subset analyses. RESULTS: Despite problems of patient compliance and
      metronidazole resistance, triple therapy with either a bismuth salt or an
      antisecretory agent plus two antibiotics appears to provide the most effective
      eradication of H. pylori (< 80%). Dual therapies such as omeprazole plus
      amoxycillin are less effective (mean 59%, range 0-92%). Reinfection rates over
      one year vary between countries from 3% in Australia and the USA to 35% in
      Ireland. Reports of ulcer recurrence during the first year after successful
      eradication range from 0 to 27%. CONCLUSIONS: There are insufficient data for
      particular doses and durations of eradication therapy from well designed
      controlled studies.

PMID- 8578234
TI  - Cholesterol gallstone formation in man and potential treatments of the
      gallbladder motility defect.
AB  - Cholelithiasis affects 10-15% of the adult population in Western society, and
      about 75% of gallstones are of cholesterol type. Hepatic hypersecretion of
      cholesterol with the formation of instable cholesterol-rich vesicles in bile, an
      imbalance between nucleation-inhibiting and nucleation-promoting proteins with
      further aggregation of cholesterol crystals in a gallbladder with a motility
      defect (stasis), all play a role in the pathogenesis of cholesterol gallstones.
      Experimental animal models suggest that gallstone formation can be prevented by
      improving gallbladder emptying. Thus, a better understanding of the causes
      underlying the impaired gallbladder motor function in patients with gallstones
      might lead to the selection of therapeutic approaches for those individuals who
      are at increased risk for the formation or recurrence of gallstones. The present
      article focuses on current concepts and theories on the pathogenesis of
      cholesterol gallstones with emphasis on the gallbladder motility defect. Several
      treatment strategies for the correction of gallbladder hypomotility are also
      discussed.

PMID- 8578235
TI  - Intestinal transplantation: a clinical update.
AB  - BACKGROUND: Until very recently the results of clinical small-bowel
      transplantation were disappointing. The latest developments indicate, however,
      that significant improvements have been made towards clinical application of this
      mode of therapy for patients with short-bowel syndrome. METHODS: Because of
      better immunosuppression and means to treat rejection, morbidity and mortality
      after small-bowel transplantation have been reduced and patient and graft
      survival has increased. RESULTS: Septic complications and abnormal intestinal
      motility with functional problems remain pertinent problems. Nevertheless, a
      significant number of recipients have been able to stop TPN and resume a normal
      diet. CONCLUSIONS: Although recent results of intestinal transplantation are
      encouraging, long-term survival is less than with other solid organ transplants.
      However, continued improvements in immunosuppression and the diagnosis of
      rejection as well as better management of functional and infectious problems will
      certainly improve future results.

PMID- 8578236
TI  - New approaches to endoscopic therapy for hemostasis of upper GI bleed.
AB  - Hematemesis and/or melena are the most common presentations of upper
      gastrointestinal bleeding. Endoscopic hemostasis after diagnosis still remains a
      challenge to the gastroenterologist. Most variceal and peptic ulcer bleeding
      episodes stop spontaneously, and then prevention of rebleeding might be indicated
      by endoscopic techniques. Four not so well known endoscopic hemostasis techniques
      are discussed and comparative studies are reviewed.

PMID- 8578237
TI  - Carcinogenesis after remote peptic ulcer surgery: the long-term prognosis of
      partial gastrectomy.
AB  - Remote partial gastrectomy for benign disease is a premalignant condition. The
      overall risk of gastric stump cancer is approximately a twofold increase, but
      patients more than 20-25 years postoperatively may have a four- to fivefold
      increased risk, compared to the age- and sex-matched general population. The
      duration of postoperative interval is the most important risk factor. For the
      first 10 years after initial surgery, gastric cancer risk may be reduced due to
      the removal of the most cancer-prone distal part of the stomach, but thereafter
      there is a rapid increase of the relative risk. The etiology and precise
      mechanism of carcinogenesis is unknown, but the time relationship with surgery
      suggests that the anatomical alterations induced by the operation must be
      important. Hypochlorhydria, reflux, diminished gastrin production, bacterial
      proliferation, and nitrosation are the putative contributing factors. In
      addition, smoking appears to contribute to a generalized cancer mortality and
      decreased life expectancy after peptic ulcer surgery. Digestive tract cancers
      other than the gastric ones which show an increased risk after peptic ulcer
      surgery are pancreatic and biliary tract cancers. Premalignant and precursor
      lesions occur more frequently in the gastric remnant after peptic ulcer surgery
      and endoscopic bioptic screening can detect early stump cancers at a curable
      stage. Large-scale screening programs of post-gastrectomy patients are
      nevertheless not recommended, and surveillance appears not justified.

PMID- 8578238
TI  - Overview of functional gut disorders: a challenge.
AB  - The term 'functional disorder' has two main meanings in the clinical realm,
      neither mutually exclusive: (i) a demonstrable disorder of function that readily
      explains the symptoms (the common wisdom in the accepted biomedical model of
      disease); and (ii) a variable combination of chronic or recurrent symptoms not
      explained by structural or biochemical abnormalities. This is a broader view that
      incorporates the concepts of illness as well as disease, and one which recognizes
      that symptoms and behavior may be out of proportion to the objective evidence of
      abnormality. The challenge is to reconcile these two apparently different views
      of a patient presenting with symptoms. In this way, investigation and management
      of a patient's symptoms can be directed not only to the underlying motor and
      sensory disorders, but also to all of the other psychosocial and cognitive
      behavioral factors that impact on the gut through the brain-gut axis and on
      patient behavior. These numerous aspects of functional gut disorders will be
      illustrated by a discussion of the factors involved in the pathophysiology of
      gastroesophageal reflux disease and of the behavior of individuals with this
      disorder.

PMID- 8578239
TI  - Individualized acute treatment strategies for gastroesophageal reflux disease.
AB  - Although gastroesophageal reflux disease is among the most common disorders seen
      by gastroenterologists, the wide variation in both its symptoms and severity has
      led to a lack of consensus about the most appropriate practical approach to
      treatment of patients with acute symptoms. This review considers the efficacy of
      the most widely used pharmacologic agents in the acute treatment of
      gastroesophageal reflux disease: H2-receptor antagonists, proton-pump inhibitors,
      and prokinetic agents. Possible treatment strategies in which they may be used
      are discussed and it is proposed that individualized treatment strategies should
      be developed based on symptoms and severity of disease. Emphasis is placed on the
      fact that, given the wide variety of effective agents available, the use of the
      same agent in every patient, regardless of their symptoms, is a most
      inappropriate approach. A stepwise approach to therapy utilizing a number of drug
      classes is discussed and the rationale for and appropriate use of both a 'step
      up' and 'step-down' approach is considered.

PMID- 8578240
TI  - Long-term management of gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease is a common disorder for which a range of
      treatment options is now available. Most information relates to short-term
      treatment, but in many respects it is questions concerning long-term management
      that cause physicians and patients most difficulty. Review of older evidence and
      some more modern studies shows that reflux disease is not invariably a chronic,
      unremitting condition and that in a significant number of patients, acceptable
      long-term management requires only intermittent symptomatic therapy or no
      medication at all. For those patients requiring continuous maintenance
      medication, current evidence implies that proton pump inhibitors, prokinetic
      agents such as cisapride and surgical treatment are the main options to be
      considered. The selection of therapeutic strategies for long-term management of
      reflux disease should involve consideration of patient preferences and opinions.
      In many cases this reveals the acceptability of a p.r.n. approach to symptom
      control, where medication is given only when required. Clinical trials and
      proposed management algorithms which presume complete symptom abolition and
      complete resolution of esophagitis to be the desirable therapeutic goals need to
      justify these assumptions in the face of evidence which seems to suggest that
      patients may think differently.

PMID- 8578241
TI  - Gastroesophageal reflux in children.
AB  - Gastroesophageal reflux is so common in infancy that the phenomenon is usually
      considered to be physiologic. However, reflux in infants has also been related to
      severe morbidity and even death. The art of selecting the optimal approach to
      treating reflux in children is to avoid over-investigations and over-treatment as
      well as the other extreme of neglecting the problem. Therefore investigations
      should be limited to a minimum and the treatment chosen should be effective but
      at the same time as free of side effects as possible. Since the basic
      pathophysiologic mechanism of reflux disease in children is a motility problem,
      prokinetic agents are indicated for the treatment of this condition. The very low
      incidence of side effects with these agents is also a relevant advantage to their
      use in the treatment of pediatric reflux disease.

PMID- 8578242
TI  - Chronic intestinal pseudo-obstruction in childhood: progress in diagnosis and
      treatment.
AB  - Chronic intestinal pseudo-obstruction is a clinical diagnosis based on signs and
      symptoms of bowel obstruction in the absence of a physical obstruction
      demonstrable by X-ray or surgery. The phenotype may be caused by gastrointestinal
      motor, sensory, or psychological disturbances, or even by Munchausen's syndrome
      by-proxy. Interactions between these pathophysiologic mechanisms may result in
      changes in the clinical presentation during development, including an increase in
      the number of affected children complaining of chronic abdominal pain. Chronic
      pain or the fear of pain may cause children to limit their voluntary oral intake,
      necessitating tube or parenteral supplements. A multidisciplinary team approach
      which includes input from the pediatric gastroenterologist, pain management
      specialist, and psychologist is most likely to effect positive change. In
      considering a diagnosis of chronic intestinal pseudo-obstruction, the clinician
      is obligated to evaluate gastrointestinal motility and sensory function, as well
      as the behavior of the child and family. This review aims to provide a
      biopsychosocial conceptual framework for understanding the heterogeneous group of
      gastrointestinal neuromuscular conditions that are diagnosed as chronic
      intestinal pseudo-obstruction. It will also provide a review and critique of the
      utility of new diagnostic methods, including antroduodenal and colonic manometry,
      and new therapeutic options, including the prokinetic agents such as cisapride
      which increase motility, and intestinal transplantation.

PMID- 8578243
TI  - Gastroparesis: diagnosis and management.
AB  - Gastroparesis occurs frequently and may be associated with gastrointestinal
      symptoms, impaired oral drug absorption and, in diabetic patients, poor blood
      glucose control. Although current knowledge of the mechanisms responsible for
      delayed gastric emptying is limited, it is clear that gastroparesis arises from a
      spectrum of motor dysfunctions. There is a poor correlation between symptoms and
      delay in gastric emptying, and objective measurement is therefore required for
      the diagnosis of gastroparesis. Scintigraphic measurement of gastric emptying is
      at present the only clinically applicable method, although other techniques,
      particularly radioisotopic breath tests and ultrasound, show considerable
      promise. Therapy with the prokinetic drugs, cisapride, domperidone,
      metoclopramide, and erythromycin, forms the mainstay of treatment. Although there
      have been few formal comparisons, cisapride is considered to be the drug of first
      choice. Current knowledge of the etiology, pathophysiology, investigation, and
      treatment of gastroparesis is discussed in this review.

PMID- 8578245
TI  - Tumors of the bladder and prostatic diseases. Papers dedicated to Hans Wolf on
      the occasion of his 60th birthday.

PMID- 8578244
TI  - Ureteric injuries. Clinical and experimental studies.
AB  - The aim of the present study was to draw up some guidelines for the management of
      ureteric injuries. Clinical studies were undertaken to identify prognostic
      factors and guide selection of the best treatment option for each patient with a
      ureteric injury, and to determine the feasibility and efficacy of endourological
      treatment in the management of these injuries. Experimental studies were designed
      to develop a new surgical bladder elongation technique for the repair of
      extensive ureteric injuries and to determine the safety of double-J ureteric
      stents currently used for endourological procedures. The influence of previous
      radiotherapy, time of treatment, and site, kind and length of the ureteric injury
      on treatment outcome was studied in 137 injuries. The length of the injury was
      found to be the most important prognosticator of treatment outcome, probably
      because extensive injuries required diversions involving a high failure rate.
      Previous radiotherapy and late treatment also had negative prognostic
      significance, probably due to their frequent association with injury length. The
      feasibility and efficacy of endourological treatment were studied in 30 injuries.
      Attempt to perform endoscopic ureteric stenting failed in 14 cases. In the 16
      successful ones, restoration of normal urinary tract and good long-term results
      were accomplished in all cases. Endourological treatment appeared to be
      particularly indicated for short injuries diagnosed early after the trauma. A new
      bladder elongation technique involving a particular Z-shaped incision of the
      bladder was studied in sheep. This bladder Z-plasty provided an average of 5.8 cm
      greater bladder elongation than the bladder psoas-hitch, with no complications or
      changes in bladder capacity. The effects of various double-J stent materials on
      pressure conditions in the upper urinary tract, on the urothelium, on urine
      precipitation (encrustation), and on urinary infection were investigated in vivo,
      in pig ureters, and in vitro, by cell cultures and bacterial adhesion assays.
      Pure polyurethane stents were found to cause long-lasting changes of renal pelvic
      dynamics and, consequently, to have deleterious effects on renal function. Stents
      made of "modified polyurethane" were found to be cytotoxic in vitro. Silicone and
      Hydro-Plus stents appeared to be the safest overall, as they caused less
      superficial epithelial destruction and host reaction than the others. Silicone
      stents, however, were found to be more prone than Hydro-Plus stents to
      encrustation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8578246
TI  - Contrast medium induced renal vasoconstriction, role of alpha receptors.
AB  - Standard imaging techniques for evaluation of renal and renovascular disease
      require the application of radiocontrast medium. The use of high osmolar, ionic
      radio contrast medium is however associated with adverse effects including acute
      renal insufficiency. Renal vasoconstriction seems to play an important role in
      the pathomechanism of this side effect. The cellular mechanisms however remain
      unsolved. Alpha 1-adrenoceptors and their subtypes are the crucial link between
      sympathetic stimulation and renal vasoconstriction. We investigated the role of
      alpha 1-receptors and the alpha 1A and alpha 1B subtypes in the renal artery and
      in sodium/meglumine diatrizoate induced renal artery smooth muscle contraction.
      Alpha 1-receptor induced rabbit renal artery contraction was produced by
      stimulation with the specific agonist phenylephrine which was antagonized dose
      dependently and reversibly by the alpha 1-blockers prazosin, terazosin and YM
      617. The alpha 1A-receptor was the prevalent receptor subtype in rabbit renal
      artery. This was identified by applying the specific alpha 1A-receptor antagonist
      5-methylurapidil and the irreversible alpha 1B-receptor antagonist
      chloroethyllonidine. These two inhibited the PE induced contraction by 96% and
      66%, respectively. Sodium/meglumine diatrizoate elicited renal artery contraction
      at 25% of the phenylephrine control. This contraction was not influenced by alpha
      1-blockers indicating the absence of an alpha 1-receptor mediated process.

PMID- 8578247
TI  - Ureteric growth in a Goettingen minipig induced by epidermal growth factor. A
      case report.
AB  - We have recently discovered that prolonged systemic administration of epidermal
      growth factor (EGF) induces a remarkable growth of all wall layers of the urinary
      tract in minipigs. In the present paper, we report the most pronounced changes
      induced by 4 weeks of systemic EGF challenge in two pigs treated for four weeks
      with either solvent or EGF (30 micrograms/kg/day), respectively. The EGF treated
      ureter was longer and thicker with an approximately four fold increase in
      diameter. All wall layers were enlarged. The urothelium was increased from 5 to
      10 cellular rows with basal hyperplasia and an increased number of goblet cells
      and cells with intracytoplasmic lumina in the luminal half. In the muscular coat,
      the bundles of hypertrophied cells and intervening connective tissue were
      enlarged. The present paper suggests a possible in vivo approach to increase the
      amount of tissue needed in reconstructive surgery of the urinary tract.

PMID- 8578248
TI  - Endoscopic diagnosis and treatment of urothelial tumors of the upper urinary
      tract.
AB  - Fifty-two percutaneous and 41 ureteroscopic procedures for upper tract tumor were
      performed in 61 patients. In 23 patients the procedure was primarily a diagnostic
      evaluation due to widespread papillomatosis or invasiveness, in the rest it was
      therapeutic. In two patients the tumor progressed and a nephroureterectomia was
      performed. Complications were minimal and transient, and no spreading of tumor
      due to endoscopy was seen. Endoscopic management is a conservative renal sparing
      treatment option in urothelial upper tract tumors.

PMID- 8578249
TI  - Percutaneous nephroscopic resection of renal pelvic tumors.
AB  - During a 7 1/2 years period 31 patients representing 32 renal units presented
      with filling defects of the renal pelvis at excretory urography. All were treated
      with percutaneous resection of the pelvis. In 26 renal units there was histologic
      evidence of transitional cell tumor of varying grade and stage. With a follow-up
      from 4 to 79 months 8 recurrences including 1 case of tract tumor implant were
      seen. No other serious procedure related or later complications have appeared.
      The indications for using the percutaneous approach are discussed, and the
      results according to grade and tumor-stage are presented. Percutaneous resection
      of renal pelvic transitional tumors is recommended for low grade, non-invasive
      tumors, and for carefully selected patients with superficially invasive tumors.

PMID- 8578250
TI  - Pelvic lymphadenectomy (staging) in patients with bladder cancer laparoscopic
      versus open approach.
AB  - In the period 01.01.93 to 01.02.95 a total number of 40 patients underwent a
      diagnostic pelvic lymphadenectomy. All patients had bladder carcinoma. Twenty-one
      had the procedure performed as an open operation and 19 had a laparoscopic
      approach. The groups were comparable as to age, sex and tumor stage. The median
      number of harvested lymph nodes was found to be the same in the two groups
      (median 5 lymph nodes). The percentage of lymph node positive patients was
      comparable -5 of 21 in the open and 4 of 19 in the laparoscopic group. One
      patient in the laparoscopy group had to be converted to an open procedure because
      of peroperative bleeding. In the open group one accidental ureteric lesion
      occurred. It was repaired intraoperatively. Only few postoperative complications
      were seen. In the open group two cases of troublesome lymphoceles occurred and
      one case of wound infection. In the laparoscopy group one patient experienced
      prolapse of an omental snip through a port incision and one patient had a scrotal
      haematoma which resolved spontaneously. The need for postoperative analgesia was
      significantly less in the laparoscopy group. The postoperative hospital stay was
      8 days in the open versus 1 day in the laparoscopy group.

PMID- 8578251
TI  - Open versus laparoscopic diagnostic pelvic lymphadenectomy.
AB  - In the staging of locally advanced bladder cancer and localized prostate cancer
      22 consecutive patients underwent open pelvic lymphadenectomy and 9 consecutive
      patients underwent laparoscopic pelvic lymphadenectomy. The two operations were
      compared with number of lymph nodes removed, operative time, hospital stay, and
      postoperative complications. By the open and laparoscopic surgery in average 5.7
      and 6.6 lymph nodes were removed, respectively. The laparoscopic procedure was
      more time-consuming, however, the hospital stay and postoperative complications
      were minor compared with the open operation. The laparoscopic pelvic
      lymphadenectomy as a staging procedure for carcinoma of the urinary bladder or
      localized prostate cancer is minimally invasive and a good alternative to open
      lymph node dissection.

PMID- 8578252
TI  - How do we follow patients with Ta grade 1-111 bladder tumors in Denmark?
AB  - A questionnaire on the follow-up regimens for Ta grade I-III bladder tumors in
      Denmark was mailed to 54 urological and surgical departments. Reply rate was 87%.
      Most patients were followed in out-patient clinics. Transabdominal ultrasound of
      the bladder was used by 9% of the departments while 36% of the departments used
      urinary cytology. Seventy-seven percent of the departments routinely took
      selected site biopsies at the primary tumor resection while only 14 departments
      (30%) used selected site biopsies during the follow-up. Forty percent of the
      departments considered carcinoma in-situ and Ta grade III malignant and Ta grade
      I and II benign while 6% regarded all four categories as malignant. A guideline
      for characterization and surveillance of bladder tumor patients is needed.

PMID- 8578253
TI  - Prolonging follow-up intervals for non-invasive bladder tumors: a randomized
      controlled trial.
AB  - Considerable resources are devoted to the follow-up of patients with superficial
      bladder tumors. Traditionally these patients are evaluated every three months in
      the first year(s) after the primary resection. In a randomised controlled design
      we evaluated the consequences of doubling the follow-up intervals for patients
      with non-invasive bladder tumors (Ta) with none of the following risk factors:
      concomitant urothelial dysplasia, tumor grade > II, early recurrence. The
      patients were allocated to one of two follow-up regimens: Regimen I: follow-up
      every three months for the first two years and every six months in the third
      year, thereafter once a year. Regimen II: Every six months for the first year and
      once a year thereafter. At most of the follow-up visits the bladder was examined
      by transabdominal ultrasound. Cystoscopy was performed in all patients once a
      year. The data from the 97 patients were evaluable. Three patients in regimen I
      and 1 patient in regimen II progressed in grade and/or stage in the observed
      period. No patient died of his tumor disease. There was no difference with regard
      to recurrence, progression and tumor-related death between the two groups. The
      total number of follow-up visits in regimen II was reduced by 37.5% (P = 0.0016)
      compared to regimen I. The number of patients specific follow-up visits with a
      recurrent tumor present was increased by 65% (P = 0.0475). In the future we will
      follow this selected group of patients with non-invasive bladder tumors as
      described.

PMID- 8578254
TI  - Metabolic acidosis: an emerging problem in patients with intestinal segments as
      part of urinary diversion. A report of two cases.
AB  - Two cases of severe metabolic acidosis are reported, one of which led to severe
      disablement of the patient due to osteomalacia. Both patients had a urinary
      diversion performed years beforehand, one consisting of a continent ileal Kock
      reservoir and the other of a urethral Kock pouch. The mechanisms of these
      complications and their treatment are discussed.

PMID- 8578255
TI  - Carcinoma implant in the abdominal wall after transurethral resection of bladder
      tumors using suprapubic trocar. A report of 3 cases.
AB  - Implantation of carcinoma cells has been described as a complication to open
      bladder resection. We present three cases in which tumor cell implantation has
      occurred after transurethral resection using suprapubic trocar.

PMID- 8578256
TI  - T-antigens in primary non-invasive and superficially invasive human urinary
      bladder tumors: the correlation to tumor recurrence and tumor progression. A mini
      review.
AB  - As cellular carbohydrate structures are involved in multiple cellular functions,
      alterations in these structures have been studied in an effort to find markers
      and predictors of the clinical course of disease in human cancers. Special
      interest has been given to recurrence and progression of cancer disease. At
      present no such marker or predictor exists for the prediction of recurrence and
      progression of initially non-invasive (Ta) or superficially invasive (T1) human
      urinary bladder tumors. Over the years the T- (Thomsen-Friedenreich) antigen (the
      disaccharide Gal beta(1-3)GalNAc alpha(1-O)-R) has been investigated for its
      possible role as such a marker. An overview is given. It is concluded that there
      is a general, but not an individual correlation between T-antigen expression and
      recurrence or progression of initially non- or superficially invasive human
      bladder tumors.

PMID- 8578257
TI  - Urethral condylomata, due to human papilloma virus (HPV) type 6/11., associated
      with transitional cell tumors in the bladder and ureter. A case report.
AB  - Condylomata in the urethra usually occur as a complication to genital warts on
      the external genitals and are most often situated in the distal part of the
      urethra. This is a report of a male patient with recurring papillomatous
      transitional cell tumors, stage Ta and T1, grade 2 and 3 in the bladder and the
      right ureter, who presented with extensive condylomatosis in the urethra from the
      meatus to the verumontanum, without simultaneous presence of condylomata at the
      external genitals. Condylomatous fragments were also present in the TUR specimen
      from the bladder, but may have been displaced from the urethra during cystoscopy.
      Using PCR technique and in situ hybridisation, HPV types 6/11 were detected in
      the condylomata, but no virus was present in the transitional cell tumors.

PMID- 8578258
TI  - A comparative study of peanut agglutinin and amaranthin binding to human urinary
      bladder tumor glycoproteins.
AB  - The reactivity of two T-antigen specific lectins, Amaranthin (ACA) and Peanut
      Agglutinin (PNA), was compared by immunohistochemical staining of serial sections
      of human bladder tumors and by Western Blot analysis of glycoproteins extracted
      from human bladder tumors prior to and after sialic acid removal. In low grade
      tumors ACA reacted prior to neuraminidase treatment. PNA on the other hand only
      showed positive reaction in these tumors after neuraminidase treatment. The two
      lectins showed identical staining patterns after neuraminidase treatment in
      tumors. In Western blottings both lectins detected a 28 kD glycoprotein. PNA also
      reacted with several other bands after neuraminidase treatment. The reactivity of
      ACA was not enhanced after neuraminidase treatment. In monosaccharide inhibition
      tests ACA- and PNA-binding to different T-antigens was most efficiently inhibited
      by GalNAc and Gal respectively. PNA binding was also inhibited by Glc, GlcNAc and
      GalNAc at higher concentrations, while the binding of ACA was only scarcely
      affected by Glc, GlcNAc and Gal.

PMID- 8578259
TI  - Radical prostatectomy versus expectant treatment for early carcinoma of the
      prostate. Twenty-three year follow-up of a prospective randomized study.
AB  - In a study by the Veterans Administration Cooperative Urological Research Group
      (VACURG), 142 patients with localized prostate cancer, VACURG stage I and II,
      were randomized between radical prostatectomy plus placebo versus placebo alone
      as initial treatment. 111 patients were evaluable for treatment comparison.
      Median follow-up for survival is 23 years. The prognostic value of Gleason
      histologic grading was confirmed. A difference in overall survival in favor of
      radical prostatectomy was observed in stage I patients. However, after adjustment
      for imbalance in age distribution, no statistically significant differences in
      survival could be demonstrated in either stage or in both stages combined. The
      results are discussed considering the small sample size and the limited
      statistical power of the study.

PMID- 8578260
TI  - The effect of castration on tumor growth rate and cell kinetics in hormone
      sensitive and hormone insensitive rat prostatic adenocarcinomas.
AB  - Cell kinetics were measured in vivo in four experimental rat prostatic
      adenocarcinomas grown in normal or castrated rats. The aim was to investigate the
      effect of castration on growth rate and cell kinetics in hormone sensitive and
      hormone insensitive prostatic carcinomas. We used two anaplastic, hormone
      insensitive, fast growing tumors (Dunning R-3327-AT1 H and E), as well as two
      well differentiated, hormone sensitive, slow growing tumors (R-3327-H and R-3327
      PAP). DNA ploidy, S-phase transit time (Ts), the labeling index (LI) and
      potential doubling time (Tpot) was determined by dual parameter flow cytometry,
      after in-vivo labeling, using bromodeoxyuridine (BUdR) and the tumor doubling
      time (DT) was determined from growth curves. After castration DT in the hormone
      sensitive H-subline changed from 21.7 days to 82.0 days, and in the PAP-subline
      from 22.2 days to 33.2 days. No significant changes in Tpot were observed. In the
      anaplastic tumors no differences in neither DT nor Tpot were seen. The cell loss
      factor (CLF) was relatively low in the two anaplastic tumors (0.55-0.59) compared
      to the well differentiated tumors. The CLF was unaffected by castration in the
      poorly differentiated tumors, whereas it increased significantly (from 0.75 to
      0.92, P = 0.005) after castration in the H-tumor, and showed a non-significant
      increase in the PAP-tumor. This implies that the decrease in tumor growth in the
      hormone sensitive tumors is due to an increase in cell death, not a decrease in
      cell proliferation. These data indicate that CLF is the dominating factor in the
      reduced growth following androgen ablation in an androgen sensitive tumor. This
      study suggests that Tpot might be an additional predictor of a tumors
      proliferating rate and it may provide important information of the human
      prostatic cancer.

PMID- 8578261
TI  - Controversies about the clinical assessment of benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a common disorder which places a
      considerable burden on older men and health care expenses. With advances in
      medical technologies and the foreseeable demographic changes in the Western
      world, the financial and epidemiological impact of this chronic disease is
      expected to increase further. The management of BPH is controversial, and this
      article critically reviews the clinical applicability and validity of the various
      measures available for assessment. Few objective modalities are indicated in the
      routine evaluation of BPH. There is a poor correlation between objective and
      subjective indicators and both measures reveal a substantial variation over time.
      This fluctuation is mainly attributed to the natural history of the disease. The
      clinical value of combining objective and subjective parameters into an analytic
      process seems small. Disagreements about the clinical value of BPH assessment
      modalities have caused inconsistent practices and consequently provision of
      changeable health care quality. Patients seek urological counseling and relief
      because of burden of illness. Quality care is provided by clinicians being
      perceptive to patients' preferences. Provision of quality care does not
      inevitably generate increasing health service expenses.

PMID- 8578262
TI  - Complications of invasive, urodynamic examinations and prostate biopsies in
      patients with benign prostatic hyperplasia.
AB  - We studied 85 men with moderate to severe symptoms of benign prostatic
      hyperplasia (BPH) who completed two placebo-controlled studies of drug therapy.
      During the 48 week period of treatment and follow-up the patients underwent 164
      procedures which included urethral instrumentation, predominantly without
      antibiotic prophylaxis, and 187 procedures of urethral instrumentation in
      combination with transperineal prostate biopsy with antibiotic prophylaxis. The
      risk for a patient to acquire clinically significant urinary tract infection was
      2.4% after urethral instrumentation alone and 7.5% when urethral instrumentation
      was combined with prostate biopsy. Invasive urodynamic examinations of prostate
      biopsies in studies of new treatment modalities for BPH should only be performed
      when necessary to obtain important information, and after full informed patient
      consent. The combination of prostate biopsy and urethral instrumentation
      increases the infection rate considerably and should be avoided.

PMID- 8578263
TI  - The role of haematuria in the diagnosis of blunt renal trauma.
AB  - In order to reevaluate the indications for an acute excretory urography (IPV)
      after blunt renal trauma, with special emphasis on the degree of haematuria, the
      medical records of 114 patients admitted to The Department of Urology, Odense
      University Hospital during a 10 year period were reviewed. Fourteen cases of
      major renal damage were revealed. Thirteen of these patients had macroscopic
      haematuria. Three of the thirteen patients were in shock and required an acute
      operation in order to stabilize their blood pressure. In one case, a thirteen
      year old girl had a major renal lesion which was diagnosed by acute IVP before
      examination of the urine. The present data support other reports in the
      literature stating that radiographic imaging is not necessary in the adult
      sustaining blunt renal trauma with microscopic haematuria and no shock. However,
      we find good reason for radiographic evaluation of all children after a blunt
      renal trauma, independent of the degree of haematuria.

PMID- 8578264
TI  - Water and solute dynamics after intravenous infusion of new irrigating fluids in
      the rabbit.
AB  - We used 25 rabbits to study blood chemistry, urinary flow and solute excretion
      for 2 h during and after intravenous infusion of 50, 75 and 100 ml/kg of 4
      solutions that have recently been introduced in Sweden for irrigation during
      transurethral operations. Infusion of mannitol 3% + ethanol 1% and sorbitol 2% +
      mannitol 1% were followed by a higher urinary flow and excretion of sodium and
      other solutes than after glycine 1.5% + ethanol 1%, glycine 1.0% + ethanol 1%,
      and normal saline (control). The volume of urine and the total solute excretion,
      but not the sodium and potassium excretion, increased with the infused volume.
      The urea and creatinine clearances increased in proportion to the urinary flow.
      Using a mathematical model, we found a volume-dependent increase in the ratio of
      extracellular to intracellular accumulation of water, although the average ratio
      was the highest for glycine 1.5% + ethanol 1% (mean 0.78) and the lowest for
      mannitol 3% + ethanol 1% (mean 0.60). We conclude that there are marked
      differences between recently introduced irrigating fluids with respect to
      diuretic effects and the distribution in the body.

PMID- 8578265
TI  - Continuous registration of blood oxygen tension during hemodialysis.
AB  - Continuous monitoring of blood oxygen tension was carried out during 45
      hemodialyses sessions. The oxygen tension curves displayed different appearances.
      Some curves presented with a periodicity like sinus curves (type 1), while others
      (type 2) fluctuated with other appearances, or displayed straight lines. Blood
      pressure variations during dialysis were significantly greater during dialyses
      displaying type 1 curves than during those displaying type 2 curves (p values <
      0.02). Due to a greater descend of S-urea during dialyses with type 1 curves than
      during dialyses with type 2 curves (p < 0.05) it is hypothesized, that the
      intensity of the dialysis treatment could be of some importance to the observed
      fluctuations in oxygen tension.

PMID- 8578266
TI  - Ambulatory 24-hour blood pressure and peptide balance in hemodialysis patients.
AB  - Blood pressure regulation during intermittent hemodialysis treatment involves
      many different mechanisms. Eight normotensive patients without antihypertensive
      drugs on intermittent hemodialysis treatment, mean age 50 years, were studied
      with 24-hour blood pressure measurements. Atrial natriuretic peptide (ANP) and
      neuropeptide Y (NPY) were determined concomitantly. Eight control individuals
      matched for age and sex were investigated in the same way. A significant increase
      of both systolic and diastolic blood pressure, heart rate and pathological
      circadian rhythm was seen among the dialysis patients. High levels of ANP were
      found before and after dialysis. NPY showed steady state levels through the 24
      hours and did not differ between the two groups. Overhydration is a probable
      cause of the disturbed blood pressure regulation and increased ANP-values.

PMID- 8578267
TI  - Long-term prognosis in idiopathic membranoproliferative glomerulonephritis.
AB  - The following results were obtained in a long-term follow-up investigation
      including 37 patients who suffered from idiopathic membranoproliferative
      glomerulonephritis. The mean follow-up period was 51 months (median 32 months).
      1) Renal survival was 35% at 5 years and 16% at 10 years. 2) Univariate analysis
      indicated significant (p < or = 0.10) association between poor prognosis and the
      two following parameters a) high age b) elevated blood pressure. 3) Using a Cox
      analysis including a) gender b) age at kidney biopsy c) square of age (age age)
      at biopsy d) presence of nephrotic syndrome e) presence of elevated blood
      pressure, the following p-values were found: 0.56; 0.02; 0.04; 0.50; 0.09. Thus
      at the 10% level age, the square of age and elevated blood pressure were
      significant and independently associated with poor prognosis.

PMID- 8578268
TI  - The treatment of ureteric calculi before and after the introduction of
      extracorporeal shockwave lithotripsy.
AB  - Indications and treatment results of ureteric calculi one year before and one
      year after the introduction of ESWL were analysed in 169 consecutive patients.
      Sex, age, former stone operation, stone localisation and stone size were not
      significantly different in the two groups. Before ESW1 47% of the patients
      received treatment against 54% after the introduction (p > 0.3). There was no
      tendency towards treatment of smaller calculi. Expectedly, the number of
      endoscopies and ureterolithotomies was significantly reduced (p < 0.05). The
      treatment period (from first contact till final control) was longer with ESWL,
      but not significantly. Judged from the length of the hospital stay there was no
      major economic benefit from ESWL. In conclusion, ESWL with a second generation
      lithotriptor is suitable for in situ treatment of ureteric calculi. It should be
      first choice for ureteric calculi.

PMID- 8578269
TI  - Recurrence rates and severity of urinary calculi.
AB  - During the last ten years, data of urinary calculi was received in 4094 cases on
      the criterion of "recurrence", whereby the answer was "yes" in 1446 cases. The
      overall "adjusted relative recurrence rate" (ARRR) is therefore 35.3%. The
      importance of an exact physical analysis of urinary stones, involving a
      differentiation of the various Ca oxalates and Ca phosphates, becomes clear
      looking at the high recurrence rates for the monomineralic stones of the Ca stone
      class like brushite and weddellite (ARRR = 66.7% and 50.0%, respectively)
      compared to apatite and whewellite (ARRR = 36.5% and 29.2%, respectively).
      Dramatic changes in the composition of the recurrent stone were observed only in
      12.7% of all cases. The highest ARRR was found in infection stones with a large
      content of struvite (about 75%), whereas the total recurrence rate of the
      infection stone class was about 38%. An assessment of the "danger" of a urinary
      stone taking into account the criteria of "composition" and "prevalence to recur"
      is given.

PMID- 8578270
TI  - Primary nocturnal enuresis: a urodynamic study spanning three generations.
AB  - The familial incidence of primary nocturnal enuresis is well recognised. Twin
      studies suggest there to be a significant genetic component to the aetiology of
      this disorder. However, family studies to date have been based on symptomatic
      enquiry alone although detrusor instability is a recognised feature of primary
      noctural enuresis in 70-80% of cases. For the first time we describe a family of
      adults with urodynamically proven instability spanning three generations. The
      pattern of inheritance lends support to the proposition that such detrusor
      instability is transmitted as an autosomal dominant characteristic.

PMID- 8578271
TI  - Clinical and urodynamic effects of propiverine in patients suffering from urgency
      and urge incontinence. A multicentre dose-optimizing study.
AB  - The efficacy and tolerability of propiverine hydrochloride (15, off 45, 60 mg/d)
      were evaluated in the treatment of 185 patients suffering from urgency/urge
      incontinence in an open, randomized, multicentre parallel-group trial lasting 21
      days. The effects on bladder volume and pressure were assessed on the basis of
      urodynamics and micturition frequency. Subjective adverse reactions were
      recorded. The bladder capacity and compliance increased and bladder pressure
      decreased in a dose dependent manner following therapy with 15, 30, 45 and 60
      mg/d. In 70% of the patients a decrease in micturition frequency was observed
      after 15 mg/d, and in 80% after 30 to 60 mg/d. Subjective anticholinergic
      symptoms were reported by 21, 40 and 28% of the patients following therapy with
      30, 45 and 60 mg/d. 15 and 30 mg were the daily doses with the most favourable
      ratio of efficacy in micturition frequency to tolerability. The results suggest
      that propiverine is a safe and effective drug for the treatment of urgency and
      urge incontinence. Individual treatment with an initial dosage of 30 mg/d should
      be recommended.

PMID- 8578272
TI  - Voiding problems in patients with HIV infection and AIDS.
AB  - The prevalence and type of urinary voiding problems were prospectively
      investigated in 77 men and four women (median age 36 years) with HIV infection or
      AIDS consecutively attending an outpatient clinic. Urologic symptoms were
      registered from replies to a questionnaire and urologic evaluation was made when
      indicated. All patients were neurologically examined. In addition, urodynamic
      data from ten consecutively referred HIV/AIDS patients were retrospectively
      analyzed. Two of the 81 prospectively studied patients had severe, and eight had
      moderate voiding problems, while 19 had pathologic findings at neurologic
      examination. Of three patients referred for urodynamic investigation, two were
      found to have neurogenic bladder dysfunction. In three of the total 13
      urodynamically studied patients the findings suggested neurogenic bladder
      dysfunction secondary to the infection. We conclude that HIV/AIDS infection
      affects voiding only in minor degree, and when it does the disease is often
      advanced and dominated by symptoms from other organs. The relevance of
      urologic/urodynamic investigation in HIV/AIDS patients thus seems limited.

PMID- 8578273
TI  - The management of urinary catheters: compliance of practice in Danish hospitals,
      nursing homes and home care to national guidelines.
AB  - The compliance of practice to national guidelines on urethral catheter care has
      been examined. Questionnaires on the practices used with patients under their
      care were sent to 1350 nursing staff. Replies were received from 1153
      individuals, 692 from hospitals, 345 from nursing homes and 116 from home care.
      While national guidelines stress the importance of maintaining a closed urine
      drainage system, the results revealed that 25.4% of respondents opened the
      drainage system to collect samples of urine for analysis, 57.9% to perform
      bladder washouts and 76% to change urine bags. 26% of respondents reported that
      they collected urine samples for routine bacteriological surveillance, a
      procedure considered unnecessary in the guidelines. 83% of staff reported that
      they washed their hands after emptying urine bags. Staff awareness of written
      guidelines for various aspects of catheter care ranged from 25-68% in hospitals,
      27-45% in nursing homes and 7-17% in home care. A marginal costs analysis was
      performed to estimate the economic consequences of non-compliance to the national
      guidelines.

PMID- 8578274
TI  - Lich-Gregoir anti-reflux procedure; indications and results with 283
      vesicoureteral units.
AB  - While reflux is not the cause of the ascension of microorganisms into the urinary
      bladder, it enables bacteria to reach the kidney and fosters pyelonephritis,
      persistent infections and nephropathy with all related consequences. The
      efficiency of the Lich-Gregoir antireflux procedure must be judged by its
      results. The criterion of success in operations upon 225 children (283
      vesicoureteral units) is the procedure's positive effect on renal growth and
      physical development of the patients by controlling pyelonephritis and the
      elimination of recurrent supravesical infections in more than 98 per cent of
      children operated upon.

PMID- 8578275
TI  - Collagen derived serum markers in carcinoma of the prostate.
AB  - Three new collagen markers deriving from the collagenous matrix, e.g.
      carboxyterminal propeptide of type I procollagen (PICP), carboxy-terminal
      pyridinoline cross-linked telopeptide of type I collagen (ICTP), and
      aminoterminal propeptide of type III procollagen (PIIINP) were used for the
      diagnose of prostatic bone metastases. Blood samples were obtained prior to
      biopsy or TURP. Serum PICP, PIIINP and ICTP were measured with commercial
      available RIAs and PSA by IRMA. Serum PSA was increased in patients with local
      prostatic cancer compared with patients with hyperplasia (p < 0.05). The level of
      PIIINP, ICTP, and PICP did not differ between these two groups. In patients with
      metastatic prostatic cancer all five markers were increased compared to the level
      measured in patients with localized cancer (p < 0.0001). All variables showed a
      significant positive relationship with alkaline phosphatase. The sensitivity
      ranged from 0.53 to 0.62 and specificity from 0.91 to 0.95. The sensitivity for
      alkaline phosphatase and PSA was 0.69 and 0.66 and specificity 0.91 and 0.68,
      respectively.

PMID- 8578276
TI  - Bilateral ureteral involvement in polyarteritis nodosa.
AB  - A case of polyarteritis nodosa with bilateral ureteral changes in IVU is
      reported, because of the rarity of ureteric involvement in this entity. The
      urographic findings were unilateral ureteral stricture with hydronephrosis and
      irregular ureter outlines bilaterally. All lesions subsided after treatment.

PMID- 8578277
TI  - Renal angiomyolipoma with extrarenal involvement--in vascular, lymph-node and
      perirenal tissue. Reports of four cases.
AB  - Extrarenal involvement was found in four cases of renal angiomyolipoma. In one
      case the wall of the inferior right bronchial artery was infiltrated, lymph nodes
      were involved in two cases and the perirenal fat in one case. Extrarenal
      extension does not seem to alter the prognosis of renal angiomyolipoma. Expectant
      treatment of this rare condition therefore appears to be warranted.

PMID- 8578278
TI  - Horseshoe kidney and aortic surgery.
AB  - A case of a 50-year-old woman with aortoiliac arteriosclerosis and an associated
      horseshoe kidney is presented. The diagnosis of this unusual combination was made
      prior to surgery; reconstruction was done by a Dacron bifurcation prosthesis.
      Ultrasonography, intravenous pyelography and aortography is important for
      "surgical planning".

PMID- 8578279
TI  - Uric acid stone formation in a patient after kidney transplantation--metabolic
      and therapeutic considerations.
AB  - The formation of urinary calculi following renal transplantation is a rare event
      with a frequency of less than 1% (4). Although 133 cases were described up to
      1988, only 5 of these had pure uric acid stones (3). We report a case in which an
      excessive purine-rich diet probably caused the stone formation. Three modalities
      of treatment were used, percutaneous nephrolithotripsy, shock wave lithotripsy
      (ESWL) and chemolysis.

PMID- 8578280
TI  - Laparoscopic diagnosis and therapy of an undescended testicle after renal
      transplantation.

PMID- 8578281
TI  - Spontaneous passage of a huge ureteric stone in a bilharzial patient.

PMID- 8578282
TI  - Prostatic cyst. An unusual but important finding in male urogenital dysfunction.
AB  - Prostatic cysts are one of the uncommon congenital disorders, and only a few
      cases have been reported. This lesion actually includes two different entities on
      the embryological development basis, the enlarged prostatic utricle and the
      cystic remnants of the mullerian ducts. We report two patients with prostatic
      cysts, probably two prostatic utricle cysts. In both cases the cyst caused
      significant urogenital dysfunction. The patients were cured by endoscopic
      unroofing of the cysts. We discuss the embryogenesis, diagnosis and treatment by
      reviewing the literature.

PMID- 8578283
TI  - Adenocarcinoma of the prostate and Eaton-Lambert syndrome. A previously
      unreported association.
AB  - Eaton-Lambert myasthenic syndrome is rare. We report the first case of
      adenocarcinoma of prostate associated with this syndrome. Subsequent treatment by
      orchidectomy caused tumour regression and remission of the syndrome. The patient
      remains well 9 months after the treatment.

PMID- 8578284
TI  - Penile gangrene: a complication of penile prosthesis.
AB  - A case of superficial gangrene of penis after insertion of a malleable penile
      prosthesis is presented. In all 4 cases previously reported in the literature,
      the penile prosthesis had to be removed. We managed this patient conservatively
      without removing the prosthesis. We suggest that in cases of superficial gangrene
      of penis without infection the prosthesis may not have to be removed.

PMID- 8578285
TI  - Leydig cell tumour in a man with human immunodeficiency virus.
AB  - We report a case of Leydig-cell testicular tumour in a 32-year-old intravenous
      drug abuser bearing HIV-infection and pulmonary tuberculosis. The testicular mass
      was initially interpreted as genital tuberculosis and the diagnosis was made by
      aspiration cytology. Radical orchiectomy was performed and pathology revealed a
      Leydig-cell tumour. Gynecomastia was found as a possible sign of endocrine
      activity. Although testicular malignancies in men with human immunodeficiency
      virus are increasingly reported, this is the first case of Leydig-cell neoplasia
      associated to HIV-infection.

PMID- 8578286
TI  - Combined therapy in a case of malignant mesothelioma of the tunica vaginalis
      testis.
AB  - Malignant mesothelioma of the tunica vaginalis testis is exceedingly rare. A new
      case mimicking hydrocele in a 47-year-old man is here reported. Clinical staging
      revealed scrotal cutaneous and funicular tumor invasion together with
      retroperitoneal adenopathies. Once visceral dissemination was ruled out, radical
      orchiectomy, left hemiscrotectomy and modified retroperitoneal lymph node
      dissection were performed. Adjuvant systemic chemotherapy and radiation were also
      administered. Histologically, an epithelial neoplasm with papillary pattern was
      evidenced. CAM 5.2 cytokeratin was positive in proliferating cells, but
      carcinoembryonic and Leu M1 antigens gave negative results. Three years later the
      patient is free of disease.

PMID- 8578287
TI  - [Diagnosis and biopsy of nonpalpable breast lesions].
AB  - In a retrospective analysis we reviewed 117 needle-localized biopsies of
      nonpalpable breast lesions in 115 women from the senologic outpatient clinic at
      the Women's Hospital of the University of Berne. In a logistic regression
      analysis, the age of the patient, the presence of grouped and irregular
      microcalcifications as well as the presence of a stellate lesion in mammography
      correlated closely with the diagnosis of breast cancer. The prevalence of
      malignant lesions, which was equal to the rate of preoperative correctly
      diagnosed malignancy in this group, was 22.2%.

PMID- 8578288
TI  - [Analysis of indications and results of fractional curettage in a large
      gynecological cohort].
AB  - AIM: To determine whether the term "fractional D&C" is justified with respect to
      the uterine cervix and corpus fractions, and what indications and results are
      found when a large population at a university hospital is analyzed. METHODS: In
      this retrospective study covering a 3-year period at the Department of
      Gynecology, University Hospital of Zurich, indications and results of fractional
      D&C were obtained from hospital records stored in a data bank. The curettage
      results of hysterectomized women were compared with the histological findings of
      the hysterectomy specimens. RESULTS: 938 women (mean age 52 years) underwent
      fractional D&C. 38% had postmenopausal, 36% premenopausal and 13% perimenopausal
      abnormal bleeding. For 5% there was a sonographic finding without bleeding
      disorders, 4% had cervical polyps, 1% breast cancer, and 3% other diagnoses. In
      13% of the cases the corpus curettage material could not be evaluated. For 43%,
      the corpus material appeared normal and in 5% a malignancy was found. In 74% of
      the cervical fractions nothing abnormal was detected, in 14% no conclusive
      evaluation of the material was possible, and in 3% the histological report showed
      a malignancy. In 20% of the cases the cervix curettage material was contaminated
      with material from the uterus cavum. CONCLUSIONS: For cases with cancer of the
      cervix, the sensitivity of fractional D&C was 80%, compared with a specificity of
      66.7%. With a positive predictive value of 52.2%, the term "fractional D&C" is in
      many cases not justified. Our data and recent literature have prompted us to draw
      up new criteria for evaluation of abnormal vaginal bleeding, or a new set of
      indications for fractional D&C and hysteroscopy.

PMID- 8578289
TI  - [25 years of dialysis and kidney transplantation in children and adolescents].
AB  - Between 1970 and 1994 84 children and adolescents with end stage renal failure
      (ESRF) were started on renal replacement therapy (RRT). Renal transplantation was
      the main goal from the beginning. The long term results were evaluated with
      emphasis on survival, development and social integration. RRT was started in
      nearly half of the children (45%) between the age of 10 and 15 years and in 14%
      before 5 years. 52 patients were first treated by hemodialysis (HD) and 27 by
      peritoneal dialysis (PD, since 1979). 5 patients underwent preemptive
      transplantation. By December 1994, 75 patients had received 99 grafts, i.e. 75
      1st, 21 2nd and 3 3rd grafts; 3 kidneys were from living related donors and 8
      patients were transplanted elsewhere. 7 patients were still on dialysis and 2 had
      died before transplantation. Actuarial patient survival (Kaplan-Meier) after
      start of RRT is 88% at 10 years and 75% at 17-25 years. Actuarial patient
      survival after first transplantation increased from 91% (1970-1984) at 5 years to
      97% (1985-1994). 7 of the first 10 patients transplanted from 1970-1974 are
      alive, all with functioning grafts (4 with their first graft). 9 patients died
      after transplantation: 4 of recurrent disease, 2 of viral (CMV, EBV) infections
      and 1 each of spinalioma, allergic shock and traffic accident. First graft
      survival was 37% at 10 years. It increased from 53% (1970-1984) to 72% (1985
      1994) at 5 years. The main causes of first graft loss (n = 33) were irreversible
      rejection (21) and recurrent disease (7). All patients aged > 22 years were
      further evaluated: patients with start of RRT 1970-1979 (group A, n = 18) were
      compared with those starting RRT from 1980-1987 (B, n = 19). Mean adult height in
      A was less than in B (163.9 cm vs 168.5 cm in men; 146.3 cm vs 156.5 cm in
      women). 50% in A vs 32% in B had a disability. Fewer patients in A (39%) than in
      B (62%) were fully employed. Considerably more patients in A (61%) than in B
      (37%) lived with their parents or siblings although the mean age in A was 31
      years vs 25 years in B. 3 women were married (all in B), 2 of them gave birth to
      3 healthy children and the third was pregnant. Long term patient and graft
      survival, somatic development and social integration have improved over the years
      due to a variety of factors. A comprehensive approach is necessary in treating
      children with ESRF.

PMID- 8578290
TI  - [Migraine: diagnosis, differential diagnosis and treatment].
AB  - Headache takes a large place in daily medical practice, and it is important to
      try and establish the most precise possible diagnosis. An outline of the
      diagnosis and differential diagnosis of migraine is followed by a discussion of
      interval drug treatment forms and counselling. Today's recommended treatment for
      attacks and the commonest sources of error in migraine management are summarized.

PMID- 8578291
TI  - [Concerning: Krahenbuhl F, Frei E: Early results of the initial 100 laparoscopic
      hernia operations under peridural anesthesia (Schweiz Med Wochenschr 1995; 125:
      1279-1285)].

PMID- 8578292
TI  - [Neuralgic shoulder amyotrophy].
AB  - The syndrome of neuralgic myatrophy of the shoulder usually presents with a
      classical clinical picture: sudden onset of intense pain in the shoulder and/or
      upper arm, followed after hours, days or weeks by (often myatrophic) paresis of
      the muscles of the shoulder region. Palsy and muscle atrophy reach their maximum
      within 4 weeks. On the basis of this typical sequence, the diagnosis was
      established in 22 patients during the period from 1983 to 1994. In agreement with
      previous observations, males represented double the number of female patients.
      The mean age at onset of the syndrome was 52.6 years (range 16-81 years).
      Possible triggering factors were registered in 11/12 patients: infections,
      abnormal physical activity or operative procedures 1-3 weeks ahead of the first
      symptoms. No preferential lateralization was noted. Most frequently paresis
      occurred in the deltoid and--in descending order--in the infraspinatus,
      supraspinatus and biceps muscles. Scapula alata was observed 7 times in 5
      patients and concomitant unilateral paresis of the diaphragm in 3 cases. In 5/22
      patients NSA was bilateral, simultaneous or successive, usually asymmetrical and
      severe. Symptoms of sensory deficit were rare and usually resolved rapidly.
      Electromyographic examination was essential for diagnosis, pointing to
      localization, follow-up and prognosis. Follow-up information was obtained in a
      majority of patients and in 17/20 cases showed a favourable course with complete
      recovery.

PMID- 8578293
TI  - [Myositis, polysynovitis and pulmonary fibrosis: anti-Jo-1 syndrome].
AB  - Polymyositis/dermatomyositis are rare autoimmune diseases. Classification is
      usually performed according to the criteria of Bohan and Peter. The occurrence of
      myositis-specific autoantibodies has recently been described in inflammatory
      myopathies. Approximately half of the patients can now be classified by these
      specific autoantibodies. Several of these autoantibodies (anti-aminoacyl-tRNA
      synthetases, anti-SRP, anti-Mi2) are strongly associated with the clinical
      presentation. We may expect that in the future different subsets of these
      diseases will be increasingly identified by serum antibodies. We report on a
      patient with myopathy, pulmonary fibrosis and polysynovitis, a typical clinical
      presentation of the anti-Jo1 syndrome (anti-synthetase syndrome).

PMID- 8578295
TI  - The epidemiology of headache and migraine, and its meaning for neurological
      services.
AB  - Estimates of the incidence and prevalence of migraine and tension-type headache
      are strongly dependent upon the diagnostic criteria employed. The inter-rater
      reliability of classification of different types of headache is poor. Whatever
      the "true" prevalence of headache and migraine, the demand for neurological
      services is culturally determined. A small alteration in tolerance of a
      population's headaches may lead to a demand for a greatly increased number of
      neurologists.

PMID- 8578294
TI  - [Treatment of osteomyelitis with oral bactericidal antibiotics-- description of 9
      cases].
AB  - The efficacy of oral bactericidal antibiotics in the treatment of osteomyelitis
      is analyzed retrospectively by a review of 9 cases histories. The first patient
      was treated in 1982. Clinical and laboratory controls were reviewed up to
      1.1.1995. In 6 patients S. aureus was isolated, while in 3 patients the organism
      could not be cultured but gram + cocci were almost likely. 5 cases of
      osteomyelitis were acute, 4 were chronic and in one case there was an infection
      of an artificial knee prothesis. The isolated S. aureus were sensitive to the
      antibiotics prescribed. 8 patients received a combination of flucloxacillin (2-4
      g/day) and rifampicin (600 mg/day); one patient was treated with the combination
      amoxicillin/clavulanic acid (1500/425 mg/day) followed by ofloxacin (400 mg/day)
      and finally co-trimoxazole (320/1600 mg/day). 3 patients received all antibiotics
      orally; in 6 patients oral administration followed a short intravenous course of
      the antibiotic combination. The duration of treatment varied between 6 and 23
      weeks. Follow-up extended over 9 months (n = 1), 14 months (n = 3), 4-7 years (n
      = 3), and 10-12 years (n = 2). In 8 cases the osteomyelitis was cured (89%). In
      our view, a combination of bactericidal oral antibiotics with good penetration
      into bone tissue can be prescribed in selected cases of osteomyelitis to shorten
      or even avoid the standard intravenous therapy of acute or chronic diseases.

PMID- 8578296
TI  - [Concerning: Thiel G: Kidney transplantation and HLA-matching: Do Swiss
      guidelines deserve to be changed? (Schweiz Med Wochenschr 1995; 125:1571-1572)].

PMID- 8578297
TI  - The death of the postmortem.

PMID- 8578298
TI  - The assessment of left ventricular function by echocardiography.

PMID- 8578299
TI  - Complications and medical comorbidities of stroke.

PMID- 8578300
TI  - The use of children's medical records to predict the risk of asthma attack.
AB  - Using a large data base of respiratory morbidity in children the opportunity
      arose to explore the link between what was written in general practice case
      records and the subsequent risk of a child developing an asthma attack or
      hospital admission due to asthma. Children with five or more consultations in one
      year for respiratory symptoms had a 33% risk of experiencing an asthma attack or
      7.1% risk of admission in the following year. Twenty seven percent of children
      who received antibiotics for "respiratory infections" subsequently had an asthma
      attack. The potential exists to review past and present symptoms and thus attempt
      to predict future morbidity. Childhood asthma is an example where the quality of
      care offered by general practitioners could be improved if a precise estimate of
      risk could be used to modify clinical management.

PMID- 8578301
TI  - Home nebuliser use in children with asthma in two Scottish Health Board Areas.
AB  - OBJECTIVE: To audit the use of home nebulisers in children with asthma. DESIGN:
      Postal questionnaire. SETTING: Two Health Board Areas in Central Scotland--one
      large industrialised city, one mixed urban and rural. SUBJECTS: 297 children with
      asthma. MEASURES EVALUATED: Initial supply and technical support for the
      compressor. EDUCATION: Pattern of drug usage. SYMPTOM CONTROL: Monitoring and
      treatment of acute attacks. RESULTS: The full burden of the home nebulised
      therapy is not being met by the NHS. Supply and servicing arrangements for home
      nebuliser therapy were poorly organised. Chronic asthma symptoms did not appear
      to be optimally controlled on present medication, with 61% reporting sleep
      disturbance in the previous three months. About 20% of parents admitted that they
      would give nebulised bronchodilator therapy more frequently than the recommended
      3 to 4 hourly. CONCLUSION: Re-organisation of resources and arrangements could
      improve the service and bring it in line with recognised standards of care.

PMID- 8578302
TI  - Assessment and referral patterns of patients admitted after deliberate self
      poisoning.
AB  - The assessment and referral patterns of adult patients after deliberate self
      poisoning in Dundee were examined. Questionnaires were completed by the admitting
      physicians and assessing psychiatrists over a 3 month period. Demographic data
      concerning the patients and the nature of self-harm were similar to previous
      studies. Initial referral rate was 95% but dropped to between 70% and 81% after
      the post receiving round. Up to 2 hours/day could be required for assessment and
      75% of the cases required some form of psychiatric follow-up. Although both
      groups of doctors considered that the majority of patients required or would
      benefit from psychiatric referral, there was poor agreement when patients were
      independently categorised into high or low suicide risk (kappa = 0.04). Agreement
      was also low regarding whether referral was essential or not (kappa = 0.06).
      Although junior medical staff can play an important role in screening of
      patients, the psychiatric service, including trained nurses, may be best placed
      to provide a full assessment, where required.

PMID- 8578303
TI  - Severe hyponatraemia associated with selective serotonin reuptake inhibitors.
AB  - Depression in the elderly is a common problem, cited as occurring in up to 10% of
      elderly people living at home, half of whom may need specialist referral. The
      introduction of selective serotonin reuptake inhibitors has been reported as a
      major advance in the treatment of depression in that they are less sedating, have
      fewer anticholinergic effects and are less toxic in overdose. We report three
      cases of severe hyponatraemia, seen in the past 12 months, associated with the
      selective serotonin reuptake inhibitors fluoxetine and sertraline. Hyponatraemia
      has been reported as a rare adverse effect of selective serotonin reuptake
      inhibitors.

PMID- 8578304
TI  - Regional survey on the management of oesophageal variceal haemorrhage.
AB  - A questionnaire was sent to 116 consultant gastroenterologists in Scotland and
      North-East England to assess their management of oesophageal variceal
      haemorrhage. Most respondents (58%) dealt with < 10 variceal bleeds per year.
      Sclerotherapy, tamponade, vasoconstrictor therapy and oesophageal transection
      were available to 87.5-97.5% clinicians, compared with trans-jugular intrahepatic
      porto-systemic shunts (TIPSS) (39.5%) and band ligation (27%). To arrest
      bleeding, sclerotherapy, tamponade, octreotide/somatostatin and
      vasopressin/glypressin were used by 75.5%, 44.5%, 37% and 32% respectively (many
      used > 1 treatment) and if bleeding continued, transection, TIPSS and shunt
      surgery were considered by 44.5%, 27% and 6%. Sclerotherapy was used for primary
      and secondary prophylaxis by 11% and 75.5%, and beta-blockers by 17.5% and 49.5%
      respectively. A wide variation in the management of variceal haemorrhage
      therefore exists. Most clinicians do not attempt to prevent primary variceal
      bleeds, with only a minority using beta-blockers but a significant number using
      sclerotherapy in this situation.

PMID- 8578305
TI  - The use of aspirin and opiates by Dumfries and Galloway general practitioners in
      the management of acute myocardial infarction.
AB  - In March 1994 a study in the British Medical Journal indicated a low rate of
      administration of aspirin and opiates by general practitioners in cases of
      suspected myocardial infarction. A retrospective analysis was made of 120
      consecutive admissions to the medical intensive care unit of Dumfries and
      Galloway Royal Infirmary, by general practitioners, with a primary diagnosis of
      acute myocardial infarction. Of these 120 cases, 24% were given aspirin by their
      G.P. prior to admission and 64% were given opiate (IV or IM). Thirty-three
      percent were already on regular aspirin and of these 18% received further aspirin
      prior to admission. These figures were considerably better than those previously
      quoted and they showed that prior regular aspirin therapy did influence the GPs'
      decision on further administration of aspirin in the acute event. A questionnaire
      sent to all GPs in Dumfries and Galloway revealed that 100% carried aspirin in
      their medical bags, 62% claimed to give aspirin to patients with suspected MI,
      95% used a British Heart Foundation approved dose of aspirin and 83.3%
      administered the aspirin using one of the approved methods.

PMID- 8578306
TI  - The Rontgen centenary.
AB  - One hundred years ago in November 1895, when Wilhelm Conrad Rontgen discovered X
      rays, a new scientific age began which has dominated our own century. Rontgen
      himself was one of the late 19th century physicists involved in the exciting
      investigations opening up at that time into the possibilities which electrical
      applications were creating. To understand the significance of Rontgen's
      discovery, it is helpful to look at the years preceding his discovery and the
      context within which his work took place.

PMID- 8578307
TI  - Determination of selenium in serum by hydride generation atomic absorption
      spectrometry for calculation of daily dietary intake.
AB  - Hydride generation atomic absorption spectrometry was used to determine the
      selenium concentrations in 130 samples of human serum from a control group of
      inhabitants in the southern part of the province of Granada (Spain). The mean
      selenium concentration in serum was 74.9 micrograms/l. This concentration did not
      vary significantly (P > 0.05) in relation to the sex of the subject, with
      concentrations of 80.6 micrograms/l in men and 70.7 micrograms/l in women. These
      mean values correspond to a mean daily dietary selenium intake of 50.4 micrograms
      per day in men and 44.6 micrograms per day in women. A considerable number of the
      individuals in the study area therefore have a daily selenium intake lower than
      the recommended dietary allowance of 70 micrograms per day for men and 55
      micrograms per day for women. Likewise, the measured selenium concentrations in
      the basic health zones of the area were not statistically different (P > 0.05).
      The differences in selenium concentration between subjects in coastal zones and
      mountainous zones are therefore not significant.

PMID- 8578308
TI  - Biotransfer and bioaccumulation of dioxins and furans from soil: chickens as a
      model for foraging animals.
AB  - Chickens were used as a model for foraging animals to examine the bioavailability
      of all 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and polychlorinated
      dibenzofurans (PCDD/PCDFs) from soil. Three groups of chickens were exposed
      through their diet to soil contaminated with PCDD/PCDFs at less than 0.5 pg/g I
      TEQ (control group), 42 pg/g I-TEQ (low exposure group), and 460 pg/g I-TEQs
      (high exposure group). Eggs, tissues, feces and feed were analysed throughout the
      exposure and depuration period. Daily intake was estimated at 2.5 ng/kg-day for
      the high and 0.3 ng/kg-day for the low exposure groups. Bioavailability was
      chlorination-dependent ranging from 80% for tetrachlorinated to less than 10% for
      octachlorinated congeners. During exposure, tissue distribution was congener
      dependent with 5-30% of the intake excreted in the eggs, 7-54% deposited in the
      adipose and less than 1% present in the liver. On a fat weight basis, the highest
      concentrations were observed in the liver, implying that mechanisms other than
      lipid solubility operate in that tissue. Bioconcentration factors and elimination
      half-lives were also congener- and tissue-dependent. Results from this study
      indicate that animals foraging on soil contaminated at low ppt PCDD/PCDF levels
      may bioaccumulate these compounds to unacceptable levels.

PMID- 8578309
TI  - Degradation of PCB in different soils by inoculated Alcaligenes xylosoxidans.
AB  - The degradation of PCB in soils by the biphenyl-utilising strain Alcaligenes
      xylosoxidans was studied in different soil types. In addition to the congener
      specificity, significant differences in the degradation of PCB by the strain in
      the different soil types were observed. Efficiency of degradation was generally
      better in sterilised soils, but the differences were not as significant as the
      differences observed between different soil types. These results indicate that
      the degradation of PCB is probably related not only to the capabilities of the
      strain employed and quality and amount of competitive species inhabiting the
      soils, but also to the soil sorption of the PCB congeners. Degradation is faster
      in the soils containing an intermediate amount of organic carbon with a high
      portion of total and aromatic carbon in humic acids.

PMID- 8578310
TI  - Pseudotumor cerebri in systemic lupus erythematosus.
AB  - OBJECTIVE: To assess the association between pseudotumor cerebri (PC) and
      systemic lupus erythematosus (SLE), and to seek a pathogenic mechanism that may
      elucidate the appearance of PC in patients with SLE. DATA SOURCE: Original
      English articles having the terms SLE, PC, or benign intracranial hypertension in
      their titles were identified by Medline search. In addition we report three new
      patients with this association. STUDY SYNTHESIS: Thirteen articles were found and
      21 patients were analyzed. DATA EXTRACTION: Of the reported 21 patients, 18 were
      previously reported and 3 new patients with coexisting PC and SLE are described.
      The clinical characteristics of the patients is presented. Patients with PC and
      SLE generally had a more severe course of SLE; renal involvement occurred in 79%,
      massive proteinuria in 47%, and hematologic abnormalities were detected in a
      third. A hypercoagulable state manifest by either recurrent thromboembolic events
      or a high anti-cardiolipin antibody titer was detected in 58% of the patients
      described. CONCLUSIONS: The association of PC and SLE is probably not
      coincidental. The high prevalence of serologic or clinical evidence of a
      hypercoagulable state suggests that microscopical thromboembolic events play a
      role in the genesis of PC.

PMID- 8578311
TI  - Adrenal insufficiency in the antiphospholipid antibody syndrome.
AB  - OBJECTIVE: Adrenal insufficiency (AI) is a rare complication of the
      antiphospholipid antibody syndrome (APS). The objective of this report is to
      describe a case and review the published literature to enhance recognition of
      this potentially fatal disorder by emphasizing its course, diagnosis, and cause.
      DATA SOURCES: A bibliographic database with the indexing terms adrenal
      insufficiency, adrenal hemorrhage, adrenal thrombosis, APS, systemic lupus
      erythematosus, with the constraints of human subjects only, was used. STUDY
      SELECTION: All 27 reports meeting the indexing terms were selected for review.
      DATA EXTRACTION: The specific criteria used for data extraction articles included
      course of the disease, causation, clinical and laboratory diagnostic criteria,
      and therapeutic intervention. DATA SYNTHESIS: Our patient is a previously health
      woman who developed a respiratory tract infection, followed by a prolonged
      illness with fever, hypotension, nausea, depression, and venous thromboses. She
      was found to have AI and APS that was alleviated with hydrocortisone and
      anticoagulation. Initially, her adrenal glands were normal on CT scan but
      subsequently became enlarged and later atrophic. Of the 27 previous case reports,
      a majority had thromboses and typical clinical and laboratory manifestations of
      AI. Hemorrhagic infarction of the adrenal gland appears to be the mechanism for
      AI in the APS. IgG and IgM anticardiolipin antibodies are most commonly reported
      in association with AI in APS. CONCLUSIONS: The hypercoagulable state in the APS
      may lead to adrenal vein thrombosis and subsequently to hemorrhagic necrosis of
      the adrenal gland. This complication of APS is important to recognize because it
      may be fatal if untreated.

PMID- 8578312
TI  - The etiopathogenesis of Sjogren's syndrome.
AB  - With increasing awareness and improved diagnostic tests, Sjogren's syndrome (SS)
      is becoming recognized as a common autoimmune disease, affecting as many as 3% of
      women over age 55 years. Apart from keratoconjunctivitis sicca, systemic features
      are common, leading to considerable morbidity and occasionally mortality.
      Predisposing factors for SS include HLA determinants that have been linked to DR3
      and heterozygosity for DQ-1 and DQ-2. There is accumulating evidence that
      activated epithelial cells and their interaction with T cells play a central role
      in pathogenesis. Some restriction of T-cell receptor gene usage to V beta 6.7b
      and V beta 13.2 and a profile of cytokine production consistent with Th-1-type
      cells has been observed in affected tissues. Antibodies to Ro (SS-A) and La (SS
      B) are found in about 50% of patients and are associated with more severe
      glandular and extraglandular manifestations. There is evidence that the
      antibodies are pathogenic, not only in patients, but in their infants born with
      congenital heart block. Studies of herpesviruses have led to conflicting results,
      and interest has recently focussed on retroviruses, based on the findings of the
      expression of retroviral elements in salivary glands of SS patients and
      antiretrovial antibodies in serum. Mice infected with or transgenic for
      retroviruses develop SS-like pathology and are currently being studied as animal
      models of the disease. In the last few years, considerable progress has been made
      in the understanding of the pathogenesis of SS, and the disease has become the
      prototype for the investigation of a viral etiology for autoimmune rheumatic
      disease. Study of its etiopathogenesis may be the key to understanding autoimmune
      disease in general.

PMID- 8578313
TI  - Vasculitides in hairy cell leukemia.
AB  - Forty-two cases of vasculitis coincident with hairy cell leukemia (HCL) have been
      reported, of which 17 had panarteritis nodosa (PAN), 21 had cutaneous
      leukocytoclastic vasculitis (LCV), and 4 had vessel wall infiltration by hairy
      cells. PAN generally occurred after the diagnosis of HCL, splenectomy, and
      infection. HBs antigen was detected in 3 of 12 patients tested, whereas immune
      complexes were positive in 3 of 4 patients tested. LCV was often preceded by
      infection and was frequently detected before HCL. Serum immunoglobulin levels
      were generally elevated when measured. Cryoglobulins, complement, rheumatoid
      factor, and antinuclear antibodies showed no clear association with vasculitis in
      HCL. These reports suggest a role for infection and splenectomy as contributing
      factors to vasculitis.

PMID- 8578314
TI  - Acute-phase proteins in osteoarthritis.
AB  - The joint destruction of osteoarthritis (OA) comprises loss of articular
      cartilage resulting from an imbalance of enzyme-catalized cartilage breakdown and
      regeneration. OA is thought to derive from defective chondrocyte metabolism and
      thus to inherently lack the large-scale systemic response that is the hallmark of
      rheumatoid arthritis (RA). Because of the apparent absence of systemic
      inflammation in OA, acute-phase response proteins have not been as extensively
      studied in OA as they have been in RA. The diagnosis of OA almost always involves
      radiographic assessment of joint damage, which is useful only after the disease
      process has been underway for several months. Radiographic evaluation cannot give
      a good assessment of current disease activity and is a relatively insensitive
      indicator of prognosis. Cartilage breakdown products can potentially serve as
      direct surrogate markers of OA disease activity, but have not been extensively
      used because of their limited sensitivity and the technical difficulties
      associated with their measurement. Markers of disease activity in RA are indirect
      and are derived from the acute-phase response, a cycle of temporal changes in
      cellular and metabolic function. The early part of the acute-phase response
      involves the local action and production of cytokines such as interleukin-1 (IL
      1), tumor necrosis factor (TNF-alpha) and IL-6. In the late acute-phase response,
      these cytokines can effect many systemic changes, including increased production
      of acute-phase proteins (APP). Three valuable surrogate markers of disease
      activity in RA are provided by the acute-phase response: the time-honored
      erythrocyte sedimentation rate (ESR) and the newer APPs C-reactive protein (CRP)
      and serum amyloid A (SAA). As in RA, the joint destruction of OA involves IL-1,
      TNF-alpha, and IL-6; however, OA can be viewed as an indolent stimulus of the
      later (systemic) acute-phase response. Recent studies of the acute-phase response
      in OA suggest that the concentrations of CRP and SAA are elevated in OA, but to a
      lesser extent than in RA. In the future, long-term monitoring of CRP
      concentrations in the blood may permit the earlier detection and more effective
      treatment of OA.

PMID- 8578316
TI  - Musculoskeletal manifestations of brucellosis: a study of 90 cases in Israel.
AB  - Rheumatological manifestations are frequently reported in patients with
      brucellosis. In a retrospective study of 90 patients diagnosed with brucellosis
      over a period of 18 years, 83 (92%) patients were Bedouins, 55 of whom (61%)
      reported ingestion of unpasteurized goat milk and goat milk products. The
      male/female ratio was 1:1, and the adult to child ratio was 3:2. The mean age of
      the patients was 25 years (range, 1-72 years). Rheumatological manifestations
      (myalgia, arthralgia, and arthritis) were reported in more than half of the
      patients. These manifestations started on days 3 and 4 of the disease and were
      mild to moderate in severity. Myalagia was evident in 49 (54%) patients and was
      more common in adults than in children (67% versus 37%; P < .01) and in men (67%)
      than in women (42%; P < .01). Arthralgia was the most common musculoskeletal
      manifestation, found in 55 (61%) patients, and occurred more often in children
      than in adults (74% versus 52%; P < .05). Arthritis was detected in 37 (41%)
      patients. The hip and knee joints were the most common sites of arthritis (31%
      each) followed by sacroiliac involvement (17%) and shoulder or spine involvement
      (5% each). Arthritis was also more common in children (63% versus 29%; P < .01).
      The prevalence of arthritis was similar in men and women. Cure was achieved in
      all patients after antibiotic therapy.

PMID- 8578315
TI  - Botanical lipids: effects on inflammation, immune responses, and rheumatoid
      arthritis.
AB  - OBJECTIVE: This review discusses the rationale and experimental data that led to
      clinical trials of certain botanical lipids, mainly gammalinolenic acid (GLA),
      for the treatment of rheumatoid arthritis (RA). DATA SOURCES: Pertinent articles
      and reviews, and a bibliographic database in English using the following indexing
      terms: rheumatoid arthritis, fatty acids, gammalinolenic acid, lymphocytes, and
      monocytes, were used. STUDY SELECTION: All clinical trials in which GLA was used
      to treat arthritis are included in this review. Data from appropriately peer
      reviewed in vitro and animal experiments evaluating the effects of botanical
      lipids as regulators of cell activation and immune responses are also reviewed.
      DATA SYNTHESIS: GLA treatment is associated with clinical improvement in patients
      with RA, as evaluated by duration of morning stiffness, joint pain and swelling,
      and ability to reduce other medications. However, studies vary in terms of
      duration, GLA dose, whether or not they were placebo controlled, and, if so, what
      placebo was used, criteria for evaluation, and use of concomitant medication.
      Studies done in vitro generally indicated that GLA reduces lymphocyte activation
      and production of mediators of inflammation. CONCLUSIONS: A small number of
      studies suggest that GLA is effective treatment for RA patients. Further
      controlled studies of its use in RA seem warranted.

PMID- 8578317
TI  - Pathology and immunopathology of primary biliary cirrhosis with emphasis on bile
      duct lesions: recent progress.

PMID- 8578318
TI  - Hepatoportal sclerosis.

PMID- 8578319
TI  - Liver biopsy in the mid-1990s: questions and answers.

PMID- 8578320
TI  - Macroregenerative (dysplastic) nodules and hepatocarcinogenesis: theoretical and
      clinical considerations.
AB  - Over the last decade or so, we have seen the development of an interesting new
      area of liver pathology, new because advanced imaging techniques coupled with
      careful screening of population at risk for HCC have focused attention on nodular
      hepatocellular lesions that have been previously ignored. Careful searching for
      these nodules has led to the acknowledgment that they are not restricted to the
      populations in which they were first identified and in which the association with
      HCC was first made, but are probably a universal phenomenon and one extremely
      important pathway for the development of HCC. Moving beyond these epidemiological
      associations, we see that careful consideration of the morphology of these
      lesions leads to insights into the early stages of human hepatocarcinogenesis,
      setting the stage for the development of a clinically useful system of
      nomenclature and, perhaps, new approaches to screening for early HCC. Additional
      important work lies ahead, as concepts from animal models of hepatocarcinogenesis
      are applied to these human lesions, molecular approaches to research and
      diagnostics are applied, and extensive prospective screening and
      clinicopathologic correlation studies are carried out.

PMID- 8578322
TI  - Blood supply of early hepatocellular carcinoma.

PMID- 8578321
TI  - Hepatocellular cholestasis: pathobiology and histological outcome.

PMID- 8578323
TI  - Biliary tumors of the liver.

PMID- 8578324
TI  - Histological classification and quantitation of the severity of chronic
      hepatitis: keep it simple!

PMID- 8578325
TI  - Special issue: Aspects of the medical care system in the People's Republic of
      China.

PMID- 8578326
TI  - Flourishing health work in China.
AB  - Great achievements have been made in China's medical and health work over the
      past 44 years. China now has become one of the leaders among the developing
      countries in respect of people's health conditions and health care service, and
      some of the fields have reached an advanced level. China owes its flourishing
      health work to the policy of 'put prevention first, rely on the progress of
      science and technology, strengthen rural health work, and give equal emphasis to
      both traditional Chinese and western medicine'. 'Health for all by the year of
      2000' has been set as a strategic goal in China, and will be accomplished through
      increased governmental investment in health work and constant reforms of the
      medical systems.

PMID- 8578327
TI  - The Chinese health care system: lessons for other nations.
AB  - This paper examines China's health care from a system perspective and draws some
      lessons for less developed nations. A decade ago, Chinese macro-health policy
      shifted its health care financing and delivery toward a free market system. It
      encouraged all levels of health facilities to rely on user fees to support their
      operations. However, China continued its administered prices and hospitals
      continued to be operated by the government. These financing, pricing and
      organizational policies were not coordinated. The author found these
      uncoordinated policies created serious dissonance in the system. Irrational
      prices distorted medical practices which resulted in overuse of drugs and high
      technology tests. Market-based financing created more unequal access to health
      care between the rich and poor. Public control of hospitals and poor management
      caused inefficiency, waste and poor quality of care. The disarray of the Chinese
      health system, however, had not caused a measurable decline in health status of
      the Chinese people. One explanation was that the government had maintained its
      level of funding (per capita) for public health and prevention. Another possible
      explanation was that rapid rising income in China had improved nutrition, clean
      water and education which offset any adverse impacts of poorer medical services
      to the low-income populations. Nonetheless, the Chinese experience showed that
      its increasing expenditure per person for health care through user fees and
      insurance had not produced commensurate improvement in health status. China'a
      experience holds several lessons for less developed nations. First, there is a
      close linkage between financing, price and organization of health care.
      Uncoordinated policies could exacerbate inequity and inefficiency in health
      care.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8578328
TI  - The reforms of the Chinese health care system: county level changes: the Jiangxi
      Study.
AB  - A survey of the economic performance of county hospitals in middle income
      counties in Jiangxi province was undertaken in 1989. The survey considered the
      impact of health policy changes in the P.R.C., especially cost recovery,
      decentralization, managerial changes and the promotion of traditional medicine.
      The financial records of county level hospitals and traditional medicine
      hospitals for the period 1980-89 were examined, as were patient expenditures.
      Opinions of those responsible for policy execution were surveyed. The data showed
      that hospitals from which state subsidy had been removed had become dependent on
      medicine sales and increasing itemization of treatment to recover costs. The
      insurance status of patients influenced the length of stay and levels of payment.
      Uninsured peasants had a shorter stay and were charged more for items of
      treatment. Traditional Medicine hospitals saw more outpatients than County
      hospitals, but were more likely to have a deficit. They were also very dependent
      on medicine sales for income. Most officials questioned felt that the changing
      system caused problems, but at the same time were eager to invest in equipment as
      a source of revenue.

PMID- 8578329
TI  - Market reforms and China's health care system.
AB  - This paper provides an overview of the medical care system in the People's
      Republic of China, and assesses the impact of market reforms on the evolution of
      the medical care system. There is clear indication that China is moving towards a
      'prepaid' system closely related to the HMO of the west. Decentralization of the
      medical care system administration has paved the way for a diversity of local
      experiments with different ways of reform, but the main direction is towards a
      integration of decisions over medical services and the insurance function. It is
      argued that reforms in this direction, while retaining a degree of socialization,
      will improve the efficiency and equity aspects of the Chinese medical care
      system.

PMID- 8578330
TI  - Urban economic reform and access to health care coverage in the People's Republic
      of China.
AB  - While the economic reforms since 1978 have brought about substantial changes in
      the rural health care system, there have been many and far-reaching implications
      for the urban health insurance system as well. This paper describes the evolving
      urban economy and examines the implications of these changes for access to health
      care coverage. Provided first is a brief description of the Chinese urban health
      care system. Three major areas of urban economic reform since 1984 are outlined
      and the possible effects of these reforms on health care coverage are discussed.
      The analysis reveals, first, the emergence of insurance coverage inequities under
      employment-based health insurance as China moves toward a open market economy.
      Second, the process of focusing on health services in rural and urban areas as
      separate systems is unnecessary and even counter-productive in light of the
      emerging integration of China's urban and rural-economies. Finally, some reasons
      for why China continues to search for employment-based health financing
      approaches are offered.

PMID- 8578331
TI  - Transformation of China's rural health care financing.
AB  - In the late 1970s China launched its agricultural reforms which initiated a
      decade of continued economic growth and significant transformation of the Chinese
      society. The agricultural reforms altered the peasants' incentives, weakened
      community organization and lessened the central government's control over local
      communities. These changes largely caused the collapse of the widely acclaimed
      rural cooperative medical system in China. Consequently China experienced a
      decreased supply of rural health workers, increased burden of illnesses,
      disintegration of the three tier medical system, reduced primary health care, and
      an increased demand for hospital medical services. More than ten years have
      elapsed since China changed its agricultural economic system and China is still
      struggling to find an equitable, efficient and sustainable way of financing and
      organizing its rural health services. The Chinese experiences provided several
      important lessons for other nations: there is a need to understand the limits of
      the market forces and to redefine the role of the government in rural health care
      under a market economy; community participation in and control of local health
      financing schemes is essential in developing a sustainable rural health system;
      the rural health system needs to be dynamic, rather than static, to keep pace
      with changing demand and needs of the population.

PMID- 8578332
TI  - The cost escalation of social health insurance plans in China: its implication
      for public policy.
AB  - China has been alarmed by its rapid rise in health care expenditures of social
      health insurance schemes. The health care expenditure per person for the 155
      million people covered by the Chinese social insurance plans has been rising at
      an accelerative rate. We analyze why health care cost in China has risen, and
      show how other nations may benefit from this experience. The annual rate of
      increase in health expenditure per capita was only 3.1% during 1952 to 1978, the
      average rate rose to 8.2% during 1978 to 1985 and then 24.4% during 1985 to 1989.
      We found general inflation explained one-half of the high rates of increase
      between 1985-1989. Although China introduced patients co-payments in 1985, the
      residual expenditure per capita (after adjusting for general inflation and aging
      of the beneficiaries) increased at 7.4% per year due to the adoption of new
      technology, uses of more expensive drugs and increased quality of services. While
      we found the expenditure increases in China were largely caused by uncontrollable
      factors such as general inflation and aging of the population, we also found the
      change in Chinese hospital financing and payment policy caused rapid adoption of
      high-tech medicine and abusive usage of more expensive drugs which largely
      explained the annual increases in expenditures of 7.4% between 1985-1989. Chinese
      experience also shows that demand strategy (co-payment by patients) had very
      little effect to contain cost escalation.

PMID- 8578333
TI  - Health care utilization as a function of subjective health status, job
      satisfaction and gender among health care workers in Guangzhou, southern China.
AB  - Job satisfaction, subjective health and health care utilization was studied on 72
      doctors and 127 nurses working at two hospitals in Guangzhou in the People's
      Republic of China (P.R.C.), along with medication use and consultations with
      physicians over the 14 days preceding data collection. Female doctors were, on
      average, ten years older than male doctors. Nurses (all female) were comparable
      to male doctors in terms of age. Current and general subjective health, and job
      satisfaction differed between doctors and nurses. Nurses were less satisfied than
      doctors and reported poorer perceived health, until gender and age were
      controlled. Female doctors had poorer ratings of general and current subjective
      health and lower job satisfaction than their male colleagues. Path analysis
      tested whether lower job satisfaction leads to decrements in perceived current
      health which in turn increased consultation with a physician and medication use.
      When male and female subjects were examined separately, job satisfaction was
      inversely related to consultation behaviour among males and positively related to
      perceived current health in both genders. Among females job satisfaction and
      consultation behaviour related to current perceived health but were not related
      to each other. The hypothesized path was upheld for nurses. Lack of power
      prevented the same path being significant for male or female doctors. In
      combination, doctors showed significant relationships between the four main
      variables studied.

PMID- 8578334
TI  - Cooperative medical schemes in contemporary rural China.
AB  - Improvements in rural health care in China in the 1950s, 1960s and 1970s were
      largely due to the development of cooperative medical schemes (CMSs) and the
      establishment of a three-tier rural health network. Since the economic reforms
      were instituted in the late 1970s, the financing and delivery of rural health
      services have seen many changes, some positive, others not. Most CMSs have
      collapsed. In the absence of CMSs, the rural population has to pay for health
      care out-of-pocket and poor families have greater difficulty in getting access to
      essential health care. In the meantime, emphases of health services have tended
      to shift from lower to higher levels, from preventive to curative services, and
      from planning and management to market forces. This paper outlines the evolution
      of CMSs, reasons for their collapse, and their likely impact on rural health
      services. The main focus is on the development of a new generation of rural
      cooperative health care schemes, given their importance in the process of
      consolidating the rural three-tier health network after the impact of the
      economic reforms: the characteristics of some schemes, the apparent conditions
      for success, and government policy towards the development of cooperative health
      care financing are presented.

PMID- 8578335
TI  - Distribution of medical insurance in China.
AB  - This paper investigates factors related to the distribution of medical insurance
      coverage in China, using information from an eight-province household survey of
      almost 16,000 individuals, conducted in 1989. Results of bivariate analyses show
      that medical insurance coverage, defined very broadly, varies considerably by
      individual and regional characteristics. Age, gender, education, occupation,
      employment sector, urbanization, level of industrial and commercial development,
      and province are all related to being insured or not. In addition, we find that
      the type of insurance program available to people varies by these same factors,
      and that the benefits provided by the seemingly uniform public and worker
      programs also vary, especially by province and degree of urban development. When
      the individual and regional variables are considered together in logistic
      regression analyses, the factors most strongly statistically related to the
      likelihood of being insured are where one works and where one lives. The
      distribution of insurance benefits in China appears to result in a pattern in
      which the rural and the poor, who are often at great risk of illness, are less
      likely to have medical insurance.

PMID- 8578336
TI  - Urban stress in China.
AB  - The stress-distress model is examined in the context of a Chinese urban center,
      Tianjin. Conceptually, the relationship between stress (as reflected in life
      events) and distress (as reflected in depressed symptoms) is hypothesized to hold
      across societies. At the same time, the measures of stress must reflect the
      social reality of a particular community of society. In the case of urban China,
      the politically-imposed stratification system arranges individuals and family
      lives around work units. These work units dictate all aspects of the life of the
      worker and his or her family, ranging from housing, major purchases, access to
      local and distance facilities, schooling and employment for children, to
      retirement pension and funeral expenses. As a result, relationships in the work
      context are expected to produce stress-inducing conflicts. Results from a
      community survey of Tianjin residents in 1986 support both the generality of the
      stress-distress model and the specificity of the effects of work-related
      stressors.

PMID- 8578337
TI  - Seeking women's voices: setting the context for women's health interventions in
      two rural counties in Yunnan, China.
AB  - If interventions to improve health are truly to benefit women, they must be
      developed from the start with a critical understanding of women's own perceptions
      of their health problems and needs, and how these concerns are linked to other
      facets of women's lives. To obtain such understanding, it is crucial for health
      planners to seek out women in the communities where they live, to encourage them
      to speak in their own voices about their health and lives, and to be genuinely
      committed to listening to what the women have to say. This paper presents results
      of focus group discussions with village women in two rural counties in Yunnan,
      China. The data are derived from 28 focus group discussions conducted by the
      Women's Reproductive Health and Development Program in Yunnan as part of a
      comprehensive assessment of reproductive health needs in poorer, more remote
      areas of the two counties. The discussions were held to ascertain what village
      women themselves feel to be their most pressing health problems, and how these
      relate to work, family, social status and their use of health services. Results
      show how women's health and their use of health services are rightly intertwined
      with their labor roles, harsh environmental conditions and oppressive poverty.
      Widespread breakdowns in the village-level primary health care network lead
      village women to express a profound lack of confidence in local health services.
      The findings have several implications for planning and implementation. Demands
      on women's scarce time need to be explicitly considered when designing health
      education activities and health service delivery.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8578339
TI  - Flows of social support and health status among older persons in China.
AB  - As a consequence of the political, social, and economic developments in
      contemporary China, there have been considerable changes in the patterns of flows
      of social support between Chinese older people and their significant others.
      There is evidence that Chinese elders are now under strong pressure to provide
      more social support, instrumental support in particular, to their children and
      other relatives while they receive less. Such a change in the direction of flows
      of social support has been reported to worsen the elders' health. This paper
      describes the general pattern of social support both to and from the Chinese
      elders, using data of a probability sample survey conducted in Wuhan, China in
      1991. The association between social support, both receiving and providing, and
      old-age health status is also analysed within a multivariate framework. The
      results of two probit models suggest that emotional support received plays a
      crucial role in affecting an elder's health status, while instrumental support
      received does not have explicit impacts. In addition, there is no empirical
      evidence that increased instrumental support from elders has worsened their
      health status as reported.

PMID- 8578338
TI  - Goods on which one loses: women and mental health in China.
AB  - This article is broadly divided into three sections. The first part deals with
      the traditional aspects of gender discrimination in China. Before the Communist
      government came to power in 1949, discrimination against women was
      institutionalized within all the usual structures of society: family, the
      economy, education, culture and the political system. It was one of the major
      policy initiatives of the Communist government to do away with unequal treatment
      of women. However, it is very easy to demonstrate that significant discrimination
      against women still exists. The Chinese government argues that this is because of
      'remnants of feudal thinking'. Although this may be partly true, there are
      aspects of current Chinese society that encourage the continuation of this
      cultural tradition. The second part of the article examines what is known of the
      epidemiology of mental illness in China with particular reference to gender. As
      is the case in Western countries, depression and neurotic disorders are diagnosed
      more frequently in women than in men, although, overall, the prevalence rate is
      much lower than in Western countries. What is unusual is that schizophrenia,
      which is diagnosed at roughly equal rates for men and women in Western countries,
      is diagnosed more frequently in women in China. Despite this, women occupy fewer
      psychiatric hospital beds and generally receive fewer resources (e.g. health
      insurance) than men. Suicide rates are very much higher in China than, for
      instance, in America, and the suicide figures for young, rural women are
      particularly disturbing. The third part of the article is based on three
      interviews with women in a psychiatric clinic in Hubei province.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8578340
TI  - Some aspects of diabetes care in Chengdu.
AB  - The great impact of diabetes mellitus (DM) on the development of China
      economically and sociomedically was firstly recognized by knowing the overall
      prevalence of the disease being 0.67% in the whole country from a nationwide
      cooperative survey in 1980. Shortly after the cooperative survey an
      epidemiological study carried out in Chengdu yielded a prevalence in DM of 1.12%,
      which was almost double the overall prevalence and slightly higher than that of
      Beijing (1.10%)--the highest one among the 14 places in the cooperative study.
      Increasing prevalence of DM is a general trend. Over the past decade the
      incidence of diabetes in hospitalized patients at the First University Hospital,
      WCUMS, increased from 5.7 to 13.54 per thousand. Factors that fluence the
      increment of prevalence of DM include increase of total calorie intake (2680
      kcal/day in 1990--close to the average world level), inappropriate high
      carbohydrate diet habit, change of life style, e.g. urbanization, mental stress,
      and ageing of the population. Primary and secondary care conducted in recent
      decades involve nutritional intervention, education via news media and workshop,
      foundation of prevention networks and providing better clinical and laboratory
      services, etc. Future improvement of diabetes care in this region is determined
      by activation of the public, motivation of the policy makers, more effective
      education and propagation by an influenced organization, fund support, man power
      and resources development, and domestic and international communications and
      collaborations.

PMID- 8578341
TI  - Outline of control practice of endemic fluorosis in China.
AB  - Endemic fluorosis is prevalent in China covering 29 provinces, municipalities and
      autonomous regions. The endemically affected areas can be divided, according to
      the sources of fluoride, into three types: high fluoride water, pollution from
      coal burning, and drinking brick tea in excess. Since the 1960's, several pilot
      surveys of the disease have been made and control programmes carried out in some
      of the areas. An Expert Consultation Committee on Endemic Fluorosis Control of
      the Ministry of Public Health was formally established in 1979. A national survey
      programme and series of working criteria for the disease were drawn up at the
      First National Congress of Endemic Fluorosis Control in 1981. Under the Central
      Government of China, administrative organizations and institutions concerned at
      all levels have been set up, forming a nation-wide network of control.
      Cooperation and coordination among such departments as health, water conservancy,
      geology and finance have been achieved in the planning and implementation of
      control programmes. Since 1980, many projects for improving drinking water
      quality through de-fluoridation have been completed. At the same time, new
      methods and technologies for improving stove and grain baking have become widely
      used in some of the areas where environmental fluoride pollution exists from
      burning coal. After all the control programmes had been introduced, the incidence
      of the illness was reduced with some patients making a complete recovery.

PMID- 8578342
TI  - The rise and prospects of medical aesthetics.
AB  - Since the 1980s, Chinese scholars have been trying to expound and synthetise
      elementary aesthetical ideas which occur in medicine, in order to treat this area
      of study as a defined branch of medicine--'medical aesthetics'. It is in this
      context that the points discussed in this paper arise. We set forth in detail the
      ideas, objectives and methods adopted within the framework of medical aesthetics
      and its applied branch--medical cosmetology and expound the relations between
      them. We think the task of medical aesthetics is to study the human body in its
      entirety, concentrating on both internal and external beauty and put the findings
      into practice, whereas the task of medical cosmetology is to study and assess
      only the external beauty of the human body and to take action on that basis.
      Medical cosmetology is the enforcement of medical aesthetics, practised in order
      to give positive results connected with physical beauty, and is therefore easily
      understood by the layman. It is known that the development of medical cosmetology
      represents an important breakthrough in the development of medical aesthetics. We
      think that beauty should not be measured mechanically, always following the same
      pattern, but that it should be considered individually with everyone's own
      particular characteristics. The quality of physical attractiveness should be
      assessed jointly by the doctor and his patient or client, not solely by either of
      these individuals nor even by a group of doctors.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8578343
TI  - Analyzing signs and symptoms of metabolic diseases.
AB  - Inborn metabolic errors, while not common, may have significant implications for
      patients. Those patients with such errors who have acute life-threatening
      symptoms must be treated immediately, and specimens for analysis should best be
      obtained during the critical stage. Many infants and children seen with acute
      symptoms are the ones most likely to have treatable diseases. At a more leisurely
      pace, other inborn errors can be diagnosed in order to provide appropriate
      counseling and prognosis.

PMID- 8578344
TI  - Neonatal circumcision: an end to the controversy?
AB  - The incidence of urinary tract infections is 10 times higher in the uncircumcised
      male than in those circumcised. An extensive review of bacterial adherence, the
      initiating factor in urinary tract infections, is presented to show that
      bacterial adherence to the prepuce is necessary for pyelonephritis to occur.
      Colonization with maternal bacteria occurs at birth; thus the incidence of
      pyelonephritis in infants born of bacteriuric mothers is much higher than it is
      in infants born of nonbacteriuric mothers. The significant morbidity of acute
      pyelonephritis in infants is one reason for encouraging neonatal circumcision,
      but a more important reason is that acute pyelonephritis in the first years of
      life often leads to significant renal damage that may progress to end-stage renal
      disease during adolescence. Since circumcision can now be done under local
      anesthesia, the newborn infant can have a painless prophylactic operation that
      will prevent urinary tract infections, pyelonephritis, and end-stage renal
      disease.

PMID- 8578345
TI  - Medical care of women deployed during Desert Storm.
AB  - The Desert Shield/Desert Storm troop deployment included record numbers of women
      and highlighted the vacuum of planning and information regarding medical care for
      women deployed to a theater of war. I review the retrievable literature from that
      conflict and discuss the data regarding resource management and clinical
      significance. The literature and my observations as an active-duty female
      gynecologist are presented to prompt a thorough systemwide evaluation of medical
      wartime readiness in light of the changing demographics of the military force.

PMID- 8578346
TI  - Aspiration of fetal pleural effusions or ascites may improve neonatal
      resuscitation.
AB  - In cases complicated by massive pleural effusions and/or fetal ascites, marked
      neonatal respiratory embarrassment may occur. Fetal centesis done just before
      delivery is useful in improving resuscitative efforts. Four cases in which the
      fetus had massive pleural effusions and/or ascites were managed by fetal centesis
      before delivery. All babies were easily resuscitated and survived the neonatal
      period. Fetal centesis should be considered immediately before delivery to
      improve resuscitative efforts and ultimately survival when significant neonatal
      respiratory compromise is likely to occur due to pleural effusions and/or
      ascites.

PMID- 8578347
TI  - Human adjuvant disease: presentation as a multiple sclerosis-like syndrome.
AB  - Twenty-six women had a systemic disease with central nervous system (CNS)
      involvement at a mean age of 39.2 years (range, 23 to 64 years) after receiving
      silicone breast implants (n = 25) or silicone fluid injections into breasts (n =
      1). The median latency period between breast surgery and onset of symptoms was
      5.71 years (range, 3 months to 15 years). All patients had evidence of
      disseminated CNS lesions; 20 patients also had evidence of peripheral neuropathy.
      Additional problems included myalgia (n = 24), joint stiffness (n = 23),
      arthralgia (n = 22), sicca complex (dry eyes and dry mouth) (n = 19), headache (n
      = 16), skin rash (n = 15), joint swelling (n = 14), Raynaud's phenomena (n = 14),
      fever (n = 13), hair loss (n = 12), allergies (n = 11), sensitivity to sunlight
      (n = 10), and lymphadenopathy (n = 9). Magnetic resonance imaging brain scans
      were abnormal in 22 of 26 patients (21, white matter lesions; 1, ischemic
      lesions; 4, cerebral atrophy). Spinal tap revealed oligoclonal bands in 18 of 23
      patients. Visual evoked responses were delayed in 14 of 23 patients, and
      autodirected antibodies were detected in 16 of 26. Sural nerve biopsy results
      showed loss of myelinated fibers in 15 of 15. Seventeen of 24 patients (71%) who
      had implant removal were found to have grossly ruptured implants. We believe our
      patients had a new syndrome triggered by the foreign material in their body. This
      syndrome appears as a systemic inflammatory autoimmune disease with central
      nervous system involvement resembling multiple sclerosis.

PMID- 8578348
TI  - Eosinophilic gastroenteritis.
AB  - Eosinophilic gastroenteritis is a rare condition of unknown etiology
      characterized by peripheral eosinophilia, eosinophilic infiltration of the
      gastrointestinal tract, and gastrointestinal symptomatology. Eosinophilic
      gastroenteritis is generally classified according to the layer of
      gastrointestinal tract involved. Mucosal involvement may result in abdominal
      pain, nausea, vomiting, diarrhea, weight loss, anemia, protein-losing
      enteropathy, and intestinal perforation. Patients with muscular layer disease
      generally have obstructive symptoms. Subserosal eosinophilic infiltration may
      result in development of eosinophilic ascites. Patients with mild and sporadic
      symptoms can be managed with reassurance and expectant observation. Patients with
      disabling symptoms can be effectively treated with corticosteroids after other
      systemic disorders associated with peripheral eosinophilia have been excluded.
      Occasionally, sodium cromolyn, ketotifen, and/or elimination diets have been
      shown to be effective in the management of patients who have a significant
      history of allergic disorder. Surgical intervention may be required in patients
      with obstructive complications or refractory disease.

PMID- 8578349
TI  - Tracheobronchial foreign body aspiration in children.
AB  - In this retrospective study, we reviewed the demographic and radiographic
      findings of 155 children with bronchoscopy-proven tracheobronchial foreign body
      aspiration (FBA). Two thirds of the patients were male, and most were children
      between 1 and 2 years of age. An aspirated peanut accounted for one third of all
      cases. Foreign body location was distributed nearly evenly to the right and left
      primary bronchi; tracheal foreign body was noted in 16 patients. The most
      frequent symptoms of FBA were cough (85 patients) and wheezing (60 patients).
      Although most patients were seen within 1 day of aspiration, 30 patients had
      symptoms that lasted at least 1 week before diagnosis. The most common
      radiographic findings were unilateral or segmental hyperlucency (59) or
      atelectasis (38). The trachea was the site of the foreign body in one half of
      children with a normal chest radiograph and FBA.

PMID- 8578350
TI  - Maternal serum amylase and lipase profiles in pregnancy: determinations in both
      once-sampled and multisampled patient cohorts.
AB  - The objective of this study was to determine the effect(s) of pregnancy and of
      advancing gestation on maternal serum amylase and lipase levels. Thus, serum
      amylase and lipase concentrations were quantitated in three groups of women.
      Groups included (1) 118 pregnant women whose serum amylase and lipase levels were
      measured once at various gestational ages ranging from 5 to 40 weeks, (2) 35
      women comprising a multisampled patient cohort whose levels were measured
      sequentially at regular intervals throughout their pregnancy, and (3) 20
      nonpregnant women of reproductive age whose levels were measured once. Results
      were statistically analyzed and trends in serum protein profiles with advancing
      gestation were charted. No significant differences were detected in either serum
      amylase or lipase concentrations as a result of pregnancy, nor were progressive
      changes noted with advancing gestation in either once-sampled or multisampled
      populations of pregnant patients. Therefore, contrary to the conclusions reached
      in some previous reports, no effects of pregnancy or of advancing gestation on
      maternal serum protein profiles were detected.

PMID- 8578351
TI  - Dysphonia in the elderly: diagnosis and management of age-related voice changes.
AB  - In our laryngology practice, we have noted an increasing number of elderly
      patients referred to us for problematic dysphonia. We present our findings of the
      most common disorder affecting this age group. A sample of 47 consecutive
      patients over age 60 with dysphonia revealed presbylaryngis, ie, age-related
      anatomic and physiologic changes, as the most common etiology found in this
      tertiary referral practice, accounting for 30% (14 patients) of new diagnoses.
      None of the patients with presbylaryngis received this diagnosis from the
      referral source. Understanding the anatomic and physiologic changes of the aging
      vocal tract, along with the clinical correlation of each change, is crucial in
      evaluating this group of patients. Managing this disorder includes specific goal
      oriented speech therapy, with surgery as an adjunct should conservative therapy
      prove unsuccessful. Earlier recognition of this disorder and prompt intervention
      are key factors in reversing vocal decompensation, with a primary effect of
      improving the quality of life for the patient with age-related dysphonia.

PMID- 8578352
TI  - Combined tracheal and esophageal trauma from gunshot wounds.
AB  - During a 5-year period between 1988 and 1993, nine patients with combined
      tracheal and esophageal injuries were treated at our institution. All injuries
      resulted from gunshot wounds and all were repaired. All patients survived, but
      complications included one tracheoesophageal fistula. Combined injuries of the
      trachea and esophagus should be repaired primarily, and drains do not necessarily
      have to be placed. The benefits of a muscle flap placed between the repairs were
      not confirmed in this series. Complications should be recognized early and
      treated aggressively to minimize damage to the airway.

PMID- 8578353
TI  - Diagnosis of thoracic outlet syndrome in the emergency department.
AB  - The use of the emergency department (ED) as a source for primary care has
      increased the number of patients seen in this setting with even chronic symptoms
      such as pain, paresthesias, and weakness in the upper extremity. This group may
      include individuals with thoracic outlet syndrome (TOS). We were concerned that
      TOS may be underdiagnosed in the ED because of physician unfamiliarity with the
      signs and symptoms of TOS. Hence, we retrospectively studied cases of TOS seen at
      the ED of the University hospital during a 29-year period. We believe this is the
      first report in the English language literature to reflect the assessment and
      management of TOS in the ED. The study data include clinical presentation,
      diagnostic tests, and management of TOS. Lack of thorough evaluation resulted in
      underdiagnosis of TOS in our ED. We recommend that ED personnel pay close
      attention to patients with symptoms of long duration and that ED physicians be
      aware of TOS presentation and its management.

PMID- 8578354
TI  - Prevention of pediatric mortality from trauma: are current measures adequate?
AB  - Trauma accounts for nearly half of pediatric deaths in the United States. We
      reviewed all pediatric trauma-related deaths that occurred over a 5-year period
      at two Georgia trauma centers to determine the number of trauma deaths in
      children, mechanism of injury, cause of death, and compliance with safety
      standards. Of the 69 fatalities, 31 were caused by motor vehicle accidents.
      Twenty-five of these victims (81%) were unrestrained; 17 were 4 years old or
      less, and only 1 of them was restrained in a car seat. Pedestrian versus vehicle
      accidents resulted in 19 deaths, 10 of the victims being 4 years old or less.
      Bicycle versus vehicle accidents resulted in 4 deaths, 2 of them due to closed
      head injury; none of the victims wore headgear. All-terrain vehicle accidents
      resulted in 2 deaths from massive head injury; neither victim wore a helmet. One
      death occurred from bicycle handlebar injury; 12 deaths resulted from causes
      other than vehicle accidents. Major causes of pediatric fatalities were motor
      vehicle accidents (45%), pedestrian-vehicle accidents (28%), and bicycle
      accidents (6%). This study indicates that when safety measures such as restraint
      systems, helmets, or proper supervision are ignored, children may die as a result
      of trauma.

PMID- 8578355
TI  - Bacteremia due to Providencia stuartii: review of 49 episodes.
AB  - We reviewed cases of Providencia stuartii bacteremia at a large community
      teaching hospital during a 12-year period (1981 to 1992). None of the infections
      were hospital-acquired. Of the 49 patients, 47 (96%) came from a nursing home,
      and 45 (92%) had a long-term indwelling Foley catheter. The urinary tract was
      definitely proven to be the source of bacteremia in 35 patients (71%) and was the
      probable source in another 5 patients (11%). Polymicrobial bacteremia occurred in
      25 patients (51%). The overall mortality rate during hospitalization was 25%.

PMID- 8578356
TI  - Treatment of mania: relationship between response to verapamil and changes in
      plasma calcium and magnesium levels.
AB  - Twelve patients meeting DSM-IIIR criteria for mania received verapamil over a 2
      week period, with dosing up to 360 mg/day. Severity of mania was measured at
      baseline and weekly by use of the Young Mania Scale. Plasma calcium and magnesium
      determinations and an ECG were obtained at baseline and after 2 weeks of
      treatment. Mean improvement was from a baseline of 32.4 to 12.8, -60.5%.
      Decreased severity of mania correlated significantly with increased plasma
      calcium. This result may lend a method for monitoring successful treatment of
      mania with calcium channel inhibitors.

PMID- 8578357
TI  - Eye patch treatment for the pain of corneal abrasion.
AB  - The traditional use of patching and topical antibiotics in the treatment of
      corneal abrasion has recently been challenged, particularly after foreign body
      removal. In a prospective, controlled, randomized study of 33 patients treated in
      the emergency department for eye pain and corneal abrasion, we attempted to
      determine whether eye patching affected the pain of simple corneal abrasions.
      After fluorescein examination with magnification (x 5), a visual analog pain
      score was recorded and the patient was randomized to either the patched or
      nonpatched group. A standard analgesic was supplied, and all patients had follow
      up at 24 hours, when repeat pain scores and analgesic use were recorded. The
      groups were compared by using the Wilcoxon's rank sum test, Student's t test, and
      analysis of covariance as required. There was no significant difference in the
      mean changes in pain scores between the patched and nonpatched groups. Analgesic
      use was also similar. We conclude that routine eye patching does not favorably
      affect the pain associated with the treatment of simple corneal abrasion.

PMID- 8578358
TI  - Screening for fever in an adult emergency department: oral vs tympanic
      thermometry.
AB  - The accuracy of tympanic thermometers in clinical practice continues to be
      questioned. We evaluated the Genius tympanic thermometer in our adult emergency
      department. All patients had both tympanic and oral temperature measurements.
      Patients with an oral or tympanic temperature > or = 100.0 degrees F had a rectal
      temperature taken. Oral and rectal measurements were taken with the IVAC 2080A
      electronic thermometer, and the Genius thermometer was used in the oral
      equivalent mode. All instruments were calibrated. Of the 332 patients entered
      into the study, 51 had oral or tympanic temperatures > or = 100.0 degrees F.
      Forty-one of these patients consented to a rectal temperature measurement. The
      correlation (r) between tympanic and oral, tympanic and rectal, and oral and
      rectal temperature was .845, .853, and .940, respectively. The oral thermometer
      identified all 28 febrile patients (rectal temperature > or = 100.4 degrees F).
      However, the tympanic thermometer detected fever in only 19 of these cases. Two
      patients in whom the tympanic thermometer failed to detect fever had AIDS, and
      their workup was altered by the detection of the fever. We conclude that the
      tympanic thermometer is not as sensitive as the oral thermometer in the detection
      of fever. The use of tympanic thermometers in the adult emergency department
      should be questioned.

PMID- 8578359
TI  - Multidrug-resistant Salmonella typhi in Pakistani children: clinical features and
      treatment.
AB  - Multidrug-resistant Salmonella typhi has become a major public health problem. In
      this study, typhoid fever was diagnosed by isolation of Salmonella typhi from
      blood or by a positive Widal's reaction in 170 Pakistani children. There were 111
      boys (65%) and 59 girls (35%). The average age was 6.2 years; 4 (2%) were less
      than 1 year old, 78 (46%) were 1 to 5 years old, and 88 (52%) were more than 5
      years old. All patients were pretreated with antibiotics. Salmonella typhi was
      detected by culture in 109 cases (64%), by Widal's test in 84 (49%), and by both
      in 23 (14%). All 79 isolates that were multidrug resistant were sensitive to
      ofloxacin, cefotaxime, and ceftriaxone. Clinical features of infections due to
      resistant S typhi did not differentiate these from other cases of typhoid. Fifty
      five infections (70%) due to resistant S typhi were treated with ofloxacin and 24
      (30%) with ceftriaxone. Sixteen patients had complications, and all recovered.

PMID- 8578360
TI  - Schwannoma of the breast.
AB  - Schwannoma arising within breast parenchyma is rare. We report such a case in a
      50-year-old woman. The tumor, which measured 7 mm, is the smallest and the only
      mammographically detected schwannoma of the breast thus far reported. Clinicians
      should be aware that this benign tumor of breast may simulate a malignant
      neoplasm clinically as well as mammographically. A review of the international
      literature yielded 15 proven cases of mammary schwannoma. Recurrence after
      surgical excision has not been reported.

PMID- 8578361
TI  - Carcinoid tumor and the nephrotic syndrome: a novel association between neoplasia
      and glomerular disease.
AB  - Various malignancies are associated with the paraneoplastic evolution of the
      nephrotic syndrome. Renal biopsy in these instances frequently shows membranous
      glomerulonephritis. We describe a patient who had metastatic bronchial carcinoid
      tumor with development of microscopic hematuria and subsequent nephrotic syndrome
      in conjunction with another paraneoplastic process, a malignancy-related
      neuropathy. A decline in actual glomerular filtration rate led to percutaneous
      renal biopsy, which revealed fine holes in the glomerular basement membrane and
      focal capillary corrugation. Electron microscopy showed numerous small
      subepithelial dense deposits and fusion of foot processes, confirming the
      diagnosis of stage I membranous nephropathy. We believe this is the first
      published case of true carcinoid tumor associated with the nephrotic syndrome and
      a specific paraneoplastic glomerular lesion. Carcinoid tumor should be considered
      in the spectrum of malignancies associated with paraneoplastic development of the
      nephrotic syndrome.

PMID- 8578362
TI  - Hemoptysis and hematemesis due to a broncholith: granulomatous mediastinitis.
AB  - A 40-year-old man had new onset of hemoptysis and hematemesis. Bronchoscopy
      revealed red, inflamed mucosa with apparent rich blood supply in the left primary
      bronchus. Computed tomography revealed calcified subcarinal lymph nodes with a
      small extension into the left primary bronchus. Shortly after admission, the
      patient had an episode of gastrointestinal bleeding. Esophagogastroduodenoscopy
      showed a lesion in the posterior wall of the esophagus, 12 cm from the upper
      incisors. During exploratory thoracotomy, a single piece of irregular-shaped tan
      tissue measuring 3.5 x 2.5 x 2.0 cm and engulfing the esophagus, carina, and left
      primary bronchus was dissected. A single stonelike mass, or broncholith, was
      found to involve both the trachea and the esophagus. Microscopic examination
      showed multiple caseating granulomas with surrounding lymphoid tissue and
      germinal centers. During 12 months of follow-up, the patient has remained
      asymptomatic. The chronic inflammation in this case suggested granulomatous
      mediastinitis, a rare disease whose mass-like effects may contribute to
      structural compression. The trachea and esophagus are rarely involved.
      Tuberculosis and histoplasmosis are thought to be the two most common causes of
      granulomatous mediastinitis. Chronic inflammation leading to calcification and
      broncholith may invade bronchial lumen or esophageal wall, causing life
      threatening hemorrhage and necessitating prompt surgical intervention.

PMID- 8578363
TI  - Methotrexate and angiographic embolization for conservative treatment of cervical
      pregnancy.
AB  - Cervical pregnancy has traditionally been treated by hysterectomy. Recent reports
      of the use of methotrexate have been encouraging as a potential conservative
      approach. We present a case of a cervical pregnancy diagnosed at 8 weeks'
      gestation in a woman who greatly desired fertility. She was treated successfully
      with a combination of multidose intramuscular methotrexate (1 mg/kg/day) and
      citrovorum rescue. When profuse bleeding developed on day 8, angiographic
      embolization was used to obviate surgery. The beta-hCG titer peaked at 58,362
      IU/mL and was undetectable by postchemotherapy day 30. No blood transfusion was
      required, and reproductive capacity was spared. Four months after the cervical
      pregnancy, the patient became pregnant and had a healthy infant. Medical
      management of cervical pregnancy is an option when reproductive capacity is
      desired in selected patients with appropriate counseling.

PMID- 8578364
TI  - Dysphagia from thoracostomy tube compression of the esophagus after single lung
      transplantation.
AB  - Esophageal compression by a thoracostomy tube is an unusual complication. Signs
      and symptoms related to this complication may begin several days after placement
      of the thoracostomy tube. We report the case of a single lung transplant
      recipient who had severe dysphagia from esophageal compression by a thoracostomy
      tube more than 1 week after tube placement.

PMID- 8578365
TI  - Is silicone safe? Let science decide.

PMID- 8578366
TI  - Managed medicine: boon or boondoggle?

PMID- 8578367
TI  - What is "normalization" of blood glucose?

PMID- 8578368
TI  - Vestibular vertigo and lovastatin therapy.

PMID- 8578369
TI  - Anatomic considerations in lumbar posterolateral percutaneous procedures.
AB  - STUDY DESIGN: Intervertebral foraminal anatomy of L2-S1 was investigated by the
      anatomic dissection of 96 foraminal levels in 12 human cadaveric spines.
      OBJECTIVES: The goal of this study was to determine the dimensions of the "safe
      zone" and a safe point of insertion in percutaneous intradiscal procedures and
      the largest safe working cannula diameter. SUMMARY OF BACKGROUND DATA: Working
      cannulas are used in percutaneous lumbar procedures. The dimensions of the safe
      zone of insertion and determination of the optimal cannula size based on these
      measurements and point of insertion are unclear from the literature. METHODS:
      Safe zone dimensions from L2-L3 to L5-S1 were determined as were two cannula
      diameters, C1 and C2. C1 was the maximal cannula size that can be placed within
      the safe zone. C2 is the maximal size allowable when the point of insertion lies
      in the midline of the pedicle. RESULTS: The average triangular safe zone was 18.9
      mm wide and 12.3 mm high; the hypotenuse measured 23.0 mm. The maximum C1
      diameter ranged 5.0-10.0 mm. The corresponding safe point of insertion lay along
      the medial one third of the pedicle. The maximum C2 diameter ranged 4.0-8.9 mm.
      The corresponding safe point of insertion lay in the midline of the pedicle.
      CONCLUSIONS: Either a 7.5-mm cannula placed in line with the medial one third of
      the pedicle or a 6.3-mm cannula located in the midline of the pedicle appears
      safe.

PMID- 8578370
TI  - Distribution of the basic fibroblast growth factor and its receptor gene
      expression in normal and degenerated rat intervertebral discs.
AB  - STUDY DESIGN: Using a rat spondylosis model, the distributions of cells
      expressing the basic fibroblast growth factor and its receptor were investigated
      in normal and degenerated intervertebral discs. Cell-proliferating activity in
      degenerated discs was also assessed. OBJECTIVES: This study was conducted to
      determine whether basic fibroblast growth factor is related to intervertebral
      disc degeneration. SUMMARY OF BACKGROUND DATA: Basic fibroblast growth factor
      stimulates proliferation and matrix synthesis of cultured intervertebral disc
      cells. METHODS: Immunohistochemistry and in situ hybridization histochemistry
      were conducted to detect cells with basic fibroblast growth factor-like
      immunoreactivity and fibroblast growth factor receptor messenger RNA,
      respectively. Cell-proliferating activity was evaluated by AgNOR staining.
      RESULTS: In degenerated discs, round chondrocytes with basic fibroblast growth
      factor-like immunoreactivity and fibroblast growth factor receptor messenger RNA
      are scattered instead of spindle-shaped cells in the normal anulus (normal anular
      cells), which are devoid of basic fibroblast growth factor-like immunoreactivity
      and fibroblast growth factor receptor messenger RNA. The proliferating activity
      of these chondrocytes is suggested to exceed that of normal anular cells.
      CONCLUSION: Basic fibroblast growth factor is suggested to promote proliferation
      of chondrocytes in degenerated discs in an autocrine or paracrine manner. Basic
      fibroblast growth factor may be related to intervertebral disc degeneration as a
      proliferation-stimulating factor of chondrocytes that replace normal anular cells
      during disc degeneration.

PMID- 8578371
TI  - Biomechanical evaluation of anterior thoracolumbar spinal instrumentation.
AB  - STUDY DESIGN: A biomechanical study was designed to assess relative construct
      stabilities of modern anterior thoracolumbar instrumentations in a calf spine
      model with an anterior and middle column defect. OBJECTIVES: The purpose is to
      compare the biomechanical stability of various anterior fixation devices in an
      unstable calf spine model. SUMMARY OF BACKGROUND DATA: Modern types of anterior
      thoracolumbar instrumentations evolved to either rods or plates. Biomechanical
      properties and comparative studies of these instrumentations are lacking.
      METHODS: Twenty fresh calf spines (L2-L5) were used for the biomechanical tests.
      L2 and L5 vertebrae were used to attach the loading and base frames,
      respectively. Specimens underwent nondestructive biomechanical tests performed
      using a three-dimensional motion measuring system. In each specimen, three
      different cases were tested: intact spine, anterior fixation with an interbody
      graft after total discectomy and endplate excision of L3-L4 disc, anterior
      fixation only without the graft. Four anterior fixators, University Anterior
      Plating System, the Kaneda device, the Z-plate, and Texas Scottish Rite Hospital
      system were used. Each device was tested on five specimens. A
      polymethylmethacrylate block was inserted into the disc space to simulate the
      interbody grafting, and a fixation device was implanted with axial compression.
      Rotational angles of the L3-L4 segment stabilized by a fixation device and graft
      were normalized by the corresponding angles of the intact specimen to study the
      overall stabilizing effects. RESULTS: With the interbody graft and fixation
      devices, all showed significant stabilizing effects in flexion, extension, and
      lateral bending. All devices restored axial rotation stability to intact
      specimen, but only the Kaneda device restored the torsional stability beyond the
      intact specimen. No statistical differences in stabilizing effects in axial
      rotation were found between any of the tested devices. When the graft was
      removed, the Kaneda device significantly decreased the motions in all directions
      compared with the intact motion, whereas the University plate decreased the
      motions in flexion, extension, and lateral bending. The Texas Scottish Rite
      Hospital system was found to reduce the flexion and lateral bending motions
      significantly, and Z-plate decreased lateral bending motions only. Stabilizing
      effects of the interbody graft were significant in lateral bendings for all
      devices. Additionally, the significant stabilizing role of the graft was noted in
      flexion and extension in Z-plate only. The graft did not significantly reduce the
      axial rotation motion in any instrumentations. CONCLUSIONS: Modern anterior
      instrumentations for the thoracolumbar spine, such as the Kaneda device, Texas
      Scottish Rite Hospital system, Z-plate, and University plate, restored the
      stability in all motions when an interbody graft was inserted. The stability of
      fixation devices revealed that the Kaneda device is the best, particularly in
      restoring the torsional stability. The information on the relative stability
      provided by different instrumentations should help the spine surgeon in choosing
      the appropriate instrumentation for the particular circumstance.

PMID- 8578372
TI  - Mechanism of the burst fracture in the thoracolumbar spine. The effect of loading
      rate.
AB  - STUDY DESIGN: Calf lumbar spine motion segments were randomly assigned to two
      groups. After insertion of a transducer capable of measuring transient occlusion
      of the spinal canal during impact, a low rate axial impact was applied in one
      group and a high rate load in the other. Post-injury computed tomography scans
      and peak canal occlusions were measured to determine the effect of rate of load
      application on occlusion of the spinal canal. OBJECTIVES: This study was designed
      to determine if for the same direction of impact and total energy delivered,
      occlusion of the spinal canal postvertebral fracture was related to the rate at
      which the impact was delivered (time from zero to peak load). SUMMARY OF
      BACKGROUND DATA: Several reports based on clinical observations have hypothesized
      that axial burst fractures, which displace bone fragments into the canal, occur
      because of internal pressurization and explosion of the vertebral body. The
      extent of bursting of the vertebra may depend on the rate of pressurization of
      the body, which could be related to the rate at which the load is applied.
      METHOD: Using calf lumbar spines, a transducer was placed within the spinal
      canal, after removal of the cord, to measure canal occlusion during impact. One
      group received axial compressive impacts at a mean loading rate of 400 msec (zero
      to peak load) using a materials-testing machine. The energy of failure was
      determined and used to select a drop weight and distance for the high loading
      rate tests, which would yield equivalent impact energy. The second group received
      impacts at a loading rate of of 20 msec. The post-injury radiographs and canal
      occlusion measurements were compared. RESULTS: The same mean energy of impact was
      used in the fractures for both groups. Post-injury radiographs of the low loading
      rate group showed compressive fractures with a mean canal occlusion of 6.84%,
      whereas the high loading rate group had burst fractures with mean canal
      encroachment of 47.6% (P = 0.0007). CONCLUSIONS: For the same energy and
      direction of impact, a high impact loading rate produces fractures with
      significant canal encroachment, whereas minimal encroachment is seen for
      fractures produced at a low loading rate.

PMID- 8578373
TI  - Why leg crossing? The influence of common postures on abdominal muscle activity.
AB  - STUDY DESIGN: Abdominal muscle activity is recorded in the supine position,
      unconstrained standing, and in the sitting position on an office chair with the
      use of backrest and armrests, with and without crossed legs. OBJECTIVES: To
      assess the role of oblique abdominal muscles in relation to the stability of
      lumbar spine and pelvis in commonly adopted unconstrained postures. SUMMARY OF
      BACKGROUND DATA: Cross-legged sitting is very common for men and women. No solid
      evidence exists for either a beneficial or a detrimental effect of this posture.
      No electromyographic study deals with the activity of abdominal muscles in this
      commonly adopted unconstrained posture. METHODS: In healthy subjects,
      electromyographic activity of the rectus abdomini and external and internal
      oblique abdominals was recorded bilaterally during commonly adopted unconstrained
      postures. RESULTS: The activity of the internal oblique muscle was significantly
      higher in the sitting position than in supine position. For the external and
      internal oblique abdominals, the activity was significantly higher in the
      standing position than in the sitting position. When sitting, the activity of the
      oblique abdominals is significantly lowered by crossing the legs in the preferred
      way (either upper legs cross or ankle on knee). In contrast, the activity of the
      rectus abdominis is not significantly altered by leg crossing. CONCLUSIONS: From
      these remarkable findings, we conclude that leg crossing is physiologically
      valuable. It should be studied whether leg crossing can be implemented in the
      design of the workplace.

PMID- 8578374
TI  - Measurement of muscle strength of the trunk and the lower extremities in subjects
      with history of low back pain.
AB  - STUDY DESIGN: Isokinetically measured muscle strength of the trunk and lower
      extremities was analyzed. OBJECTIVES: The causes of the weak trunk muscle
      strength of subjects with low back pain were studied. SUMMARY OF BACKGROUND DATA:
      Although it is a commonly accepted conclusion that subjects with low back pain
      have weaker trunk muscles than the normal population, there are no reports
      concerning muscle strength of the lower extremities in subjects with low back
      pain. METHODS: Ninety-eight male volunteers were divided into control groups and
      groups with low back pain. The total trunk strength and total knee strength were
      defined as the sum of the peak torques of trunk extension, flexion and rotation,
      and of bilateral knee extension and flexion, respectively. RESULTS: The total
      trunk and knee strength in the group with low back pain (281 +/- 170 and 301 +/-
      132 Nm) were significantly lower than in the control group (543 +/- 124 and 441
      +/- 123 Nm). The total trunk and knee strength were linearly correlated in both
      groups (r = 0.67 and 0.79). CONCLUSIONS: In the group with low back pain, the
      muscles of the trunk and the lower extremities were similarly affected; this can
      be attributed to generalized muscular weakness or psychologic factors, such as
      fear of injury.

PMID- 8578375
TI  - Outcome of unoperated discogram-positive low back pain.
AB  - STUDY DESIGN: No previous discography study has addressed the nonoperative
      outcome of low back pain. OBJECTIVES: This study was undertaken to
      retrospectively analyze the outcome of patients with documented single-level
      discogenic pain who were considered candidates for surgery but did not receive
      it. SUMMARY OF BACKGROUND DATA: The natural history of "discogenic" low back pain
      is unknown, and its treatment is controversial. Although positive discography is
      viewed as a valid diagnostic technique, the results of fusion surgery are often
      disappointing. METHOD: Twenty-five individuals (16 women, 9 men) underwent
      comprehensive evaluation (examination, radiography, objective disability
      determination). Study criteria included incapacitating low back pain, single
      level + morphologic + provocative discogram, no surgery, and a minimum follow-up
      period of 3 years. RESULTS: Average age of patients at discography was 43 years
      and at study was 48 years; level of involvement in 10 patients was L4-L5 and in
      15 patients were L5-S1. The mean follow-up period was 4.9 years (range, 3.3-7.0
      years). The condition of 17 (68%) patients improved, two (8%) stayed the same,
      and six (24%) worsened. Improved patients had a shorter history of low back pain
      (3.5 yr vs. 11.0 yr) and older age at onset (45 versus 33 yrs.) Psychiatric
      disease was present in 66.7% (4 of 6) patients whose conditions worsened. Eighty
      percent (12 of 15) of patients receiving workers' compensation improved. There
      was no correlation between disc level, gender, smoking, and outcome. CONCLUSIONS:
      Discogenic low back pain improved in patients without psychiatric disease. Older
      age at onset and shorter duration of low back pain were favorable indicators.
      These results are comparable with or better than those reported for surgical
      treatment of this condition.

PMID- 8578376
TI  - Health outcome assessment before and after adult deformity surgery. A prospective
      study.
AB  - STUDY DESIGN: Fifty-five patients undergoing surgery for adult spinal deformity
      assessed their health status using a generic health outcome instrument before
      surgery and at an average of 2 years after surgery. OBJECTIVE: To assess whether
      adult spinal deformity surgery is a useful intervention when patients evaluate
      their own perception of health. The Medical Outcomes Survey Short Form-36, a
      validated generic health outcome assessment form, was used to measure patient's
      health status. SUMMARY OF BACKGROUND DATA: Surgery for adult scoliosis is
      technically demanding. No study that we are aware of uses a generic health
      outcome instrument in a prospective manner to compare patients' perception of
      their health after adult scoliosis surgery. The Medical Outcomes Survey Short
      Form-36 has been validated in multiple studies assessing other medical conditions
      and was found to be reliable, comprehensive, brief, and generic. METHODS: Sixty
      eight adult patients undergoing surgery for adult spinal deformity were
      prospectively enrolled. Fifty-five patients were available to complete the
      Medical Outcomes Surgery Short Form-36 after surgery. The scores of the health
      profile were compared before and after surgery. The results of patients younger
      than 40 years were compared with those of patients older than 40 years. The
      results of patients younger than 40 years were compared with those of patients
      older than 40 years. The results of patients fused to more caudal end vertebral
      levels ((L4, L5)5) were compared with those who were fused to more cranial end
      vertebral levels. The results of patients without complications after surgery
      were compared with those of patients with complications after surgery. RESULTS:
      Average follow-up period was 22.5 months (minimum 12 months) in 82% of 68
      patients. Statistically significant improvements were seen in postoperative
      scores for physical function, social function, bodily pain, and perceived health
      change. We found no significant differences in self-reported health function
      parameters related to age ( > 40 vs. < 40), end vertebral level of fusion, or
      presence of complications after surgery. CONCLUSIONS: Applying a generic health
      outcome instrument to adult spinal deformity surgery shows that adult scoliosis
      surgery significantly improves patient self-reported health assessment and
      function. Beneficial results do not appear to deteriorate with age or more caudal
      end vertebral levels of fusion. Future studies combining disease-specific
      outcomes analysis and generic health surveys to assess end results of adult
      spinal deformity surgery will be useful.

PMID- 8578377
TI  - Construction and validation of a specific quality of life instrument for
      adolescents with spine deformities.
AB  - STUDY DESIGN: The development and construction of a specific instrument for
      measuring quality of life in adolescents with spine deformities was investigated.
      OBJECTIVES: To assess the validity and reliability of the Quality of Life Profile
      for Spine Deformities. SUMMARY OF BACKGROUND DATA: An 88-item questionnaire was
      self-administered to 174 patients ranging in age from 10 to 20 years with spine
      deformities. Items were rated on a five-point Likert scale. Higher scores means
      high level of impairment in quality of life. Age, gender, menarche or voice
      change, salient symptoms in the medical record, ordinary parameters on physical
      examination, and measurements on standard anteroposterior and lateral radiographs
      were recorded. The retest was done 10 days after the initial administration in a
      subsample of 35 patients. METHODS: The test-retest reliability was analyzed
      calculating the intraclass correlation coefficient. Internal consistency was
      measured with the Cronbach's alpha method. Factor analysis was used to obtain a
      reduced number of variables. Construct validity was assessed using the principal
      components model of factor analysis based on the correlation matrix and using the
      varimax computer algorithm for orthogonal rotation. Discriminant validity was
      assessed using the Kruskal-Wallis test. RESULTS: The Quality of Life Profile for
      Spine Deformities contained 21 items and five factors in conceptual terms labeled
      psychosocial functioning, sleep disturbances, back pain, body image, and back
      flexibility. The overall questionnaire score showed an internal consistency of
      0.88 and a test-retest correlation of 0.91. Patients with structural curves
      showed significantly higher scores in all dimensions of the Quality of Life
      Profile for Spine Deformities except for the subscale of body image than patients
      with postural curves. When patients were grouped according to the symptom of back
      pain, those with backache had a significantly higher quality of life overalls
      score and scores in the dimensions of sleep disturbances and pain. Brace-treated
      patients showed statistically significant differences in the quality of life
      overall score and scores in the dimensions of psychosocial functioning and back
      flexibility. CONCLUSIONS: The instrument developed for measuring quality of life
      in patients with spine deformities during the period of bone growth has validity,
      internal consistency, and high test-retest reliability. The conceptualization of
      quality of life of the Quality of Life Profile for Spine Deformity includes
      psychosocial dimensions and pain and function.

PMID- 8578379
TI  - Chemonucleolysis versus laminectomy. A cohort comparison of effectiveness and
      charges.
AB  - STUDY DESIGN: A prospective cohort study was done comparing 100 consecutive
      chemonucleolysis patients with 100 consecutive laminectomy patients. OBJECTIVES:
      The effectiveness and cost of chymopapain chemonucleolysis was compared with that
      of laminectomy to manage herniated lumbar discs. SUMMARY OF BACKGROUND DATA:
      Although the efficacy of chemonucleolysis has been established, controversy
      regarding the relative benefits of chemonucleolysis and laminectomy continues to
      arise. The relative cost-effectiveness of the two procedures has not been
      evaluated previously in a cohort study. METHODS: Patients in both treatment
      groups were of comparable age, height and weight, and worker's compensation
      status. Patients with migrated disc were not considered for chemonucleolysis.
      Improvement in pain, paresthesia, straight-leg raising, reflexes, motor loss, and
      sensory function, self-reported overall improvement, ability to maintain
      employment, and charge of treatment were used to measure treatment success.
      RESULTS: Clinical assessment after 6 weeks showed 92% of laminectomy patients
      compared with 82% of chemonucleolysis patients compared with 82% of
      chemonucleolysis patients had successful results (P = 0.058). Chemonucleolysis
      patients had greater improvement in numbness (P = 0.014) and sensory and motor
      functions (P = 0.002). After 6 months, 88% of chemonucleolysis patients and 85%
      of laminectomy patients had successful results, with a greater improvement in
      sensory status of chemonucleolysis patients and 82% of laminectomy patients had
      successful results, and more chemonucleolysis patients than laminectomy results,
      the average charge savings for chemonucleolysis patients was +5365 when
      chemonucleolysis was performed instead of laminectomy. CONCLUSION: This study
      shows that chemonucleolysis is an effective as laminectomy in appropriately
      selected patients but at lower charge and can contribute substantially to
      reducing short-and long-term health costs.

PMID- 8578378
TI  - Motor affliction of the L5 nerve root in lumbar nerve root compression syndromes.
AB  - STUDY DESIGN: From a prospective and consecutive study on degenerative lumbar
      spine disorders containing 416 patients, all patients with a severely reduced or
      absent strength of the extensor hallucis longus muscle (n = 35) before surgery
      were identified. OBJECTIVES: The incidence, diagnosis, and recovery after surgery
      of patients with L5 root compression syndromes and a severely reduced or absent
      power before surgery of the big toe extensor was evaluated. SUMMARY OF BACKGROUND
      DATA: The L5 root is commonly involved in disc herniation and central and lateral
      spinal stenosis. Whether motor recovery occurs after root decompression is not
      fully known. METHODS: All patients underwent a conventional radiologic evaluation
      before surgery including one or more myelography, computed tomography scan, and
      magnetic resonance imaging. At examination before surgery, extensor hallucis
      longus-power was graded as normal, reduced, or severely reduced/absent, and the
      latter group is presented here. Surgical findings were registered. Clinical
      investigation was performed after 4, 12-, and 24-month follow-up periods.
      RESULTS: A pronounced extensor hallucis longus paresis was seen in disc
      herniation in 20 of 187 patients, in lateral spinal stenosis in 10 of 122
      patients, and central spinal stenosis 5 of 107 patients. Improvement of the
      paresis after surgery was equally common in disc herniation (15 of 20 patients)
      and lateral spinal stenosis (7 of 10 patients). Complete restitution was more
      common in disc herniation. None of the five patients with central spinal stenosis
      improved concerning paresis at the follow-up period. Improvement was most common
      during the first 4 months after surgery. No correlation between age or
      preoperative symptom duration and recovery was noted in either group. CONCLUSION:
      The incidence of pronounced extensor hallucis longus paresis in lumbar nerve root
      compression varied between 5-11%. Recovery after surgery was common in disc
      herniation and lateral spinal stenosis but did not occur in central stenosis.
      Complete recovery was most common in disc herniation, and recovery occurred
      mainly during the first 4 months after surgery.

PMID- 8578380
TI  - Effects of spinal instrumentation on fusion of the lumbosacral spine.
AB  - STUDY DESIGN: This study retrospectively, reviewed the effects of pedicle screw
      fixation on lumbosacral fusion for degenerative conditions. The records and
      radiographs of a group of patients treated by wide decompression and fusion of
      the lumbosacral spine and by one surgeon were studied. Two treatment groups were
      identified by fusion technique; one group received autologous bone graft only,
      and second group was treated by autologous bone grafting supplemented with
      pedicle screw fixation. OBJECTIVES: The two study groups were compared to
      determine the effects of pedicle screw fixation on lumbosacral fusion for
      degenerative conditions after wide decompression. SUMMARY OF BACKGROUND DATA: The
      reported success rate of lumbar and lumbosacral fusion in the literature is
      variable. Although several studies have reported high fusion rates with internal
      fixation, few controlled studies have been published. A critical review of
      isolated lumbosacral fusions (for degenerative conditions) and the effects of
      instrumentation is necessary to determine the effectiveness and complications
      associated with pedicle screw systems in this setting. METHODS: This study
      reviewed 215 consecutive patients operated on from 1987 to 1992 for degenerative
      conditions of the lumbosacral spine. Group 1 included 126 patients who underwent
      autogenous posterolateral bone graft after decompression. Group 2 included 89
      patients treated with Edwards instrumentation and autogenous bone graft. Fusion
      status was determined via radiographs. Clinical results were based on pain relief
      after a minimum 2-year follow-up period. RESULTS: In Group 1, an overall fusion
      rate of 65% was obtained. Clinically, 56% had good or excellent results.
      Complications included pseudarthroses (35%), dural tears (3.2%), and infection
      (2.4%). In Group 2, a fusion rate of 91% was achieved. In this group, 89% had a
      good or excellent clinical result. Complications included pseudarthroses (9%),
      dural tears (2.2%), and infection (2.2%). CONCLUSIONS: Use of pedicle screw and
      rod fixation with the Edwards system led to significantly improved results in
      lumbosacral fusions over autogenous bone graft alone, with a lower complication
      rate. The use of spinal is a valuable adjunct to achieve lumbosacral fusion in
      patients who have undergone decompressive surgery for the spine.

PMID- 8578381
TI  - Instrumented laparoscopic spinal fusion. Preliminary Results.
AB  - STUDY DESIGN: Seventeen consecutive patients underwent laparoscopic instrumented
      interbody fusions using custom-designed delivery instrumentation and "BAK" fusion
      cages; both are manufactured by Spinetech and the former was developed by the
      authors. The cases were performed at two spine centers under Food and Drug
      Administration investigational device evaluation clinical trials. OBJECTIVES: We
      expect this approach will maintain a high fusion rate with diminished
      hospitalization time, recovery time, patient discomfort, and expense. The
      rehabilitative aspects of the procedure are a great improvement over traditional
      fusion approaches. SUMMARY AND BACKGROUND DATA: Extraordinary advances in many
      endoscopic surgical fields have resulted in many endoscopic surgical fields have
      resulted in lowered morbidity, expense, and suffering associated with their open
      surgery counterparts. The authors have developed prototype of delivery
      instruments for the current laparoscopic fusion cage delivery system. METHODS:
      The procedure is performed transperitoneally with carbon dioxide insufflation to
      enable video-assisted visualization through a 10-mm endoscope. Three 10-mm
      incisions and one 13- to 20-mm incision are required for one-level procedures.
      Two hollow titanium-threaded interbody implants are packed with autologous bone
      and inserted into the diseased interspace. RESULTS: Seventeen patients, with an
      average follow-up period of 8 months and a range of 6-12 months, underwent the
      procedure. There were 14 single-level fusions and three two-level fusions, all
      involving L4-S1 levels. There were two cases that required conversion to open
      procedures without sequelae; two patients had remote donor site wound infections
      eradicated with incision and drainage and antibiotics, and one patient required
      subsequent posterior spinal decompression because of a displaced endplate
      fracture. Average hospital stay was an average of 2 days, excluding two patients
      with complications and very prolonged stay. CONCLUSIONS: Although this procedure
      is associated with a long learning curve, the technique, once mastered, is
      effective and advantageous over current approaches to lumbar fusion. Operative
      time and hospital stay are expected to decrease with future instrumentation
      development and surgeon experience.

PMID- 8578382
TI  - Intradural extramedullary ependymoma. A case report.
AB  - STUDY DESIGN: The present study illustrates a rare case of ependymoma of the
      spinal cord. OBJECTIVES: An encapsulated intradural extramedullary ependymoma of
      the cervicothoracic spinal cord in a 24-year old woman is reported. SUMMARY OF
      BACKGROUND DATA: Ependymoma is a glial tumor arising in the central nervous
      system. Intradural extramedullary ependymoma of the spinal cord is rare, and two
      cases were reported previously. METHODS: The woman presented with myelopathy
      below C6. Magnetic resonance imaging showed an intradural tumor from C4 to T3 and
      no other lesion in the central nervous system. At surgery, the extramedullary
      tumor apparently was not attracted to the spinal cord or dura mater. Gross total
      removal was easily achieved under the operating microscope. RESULTS: Histologic
      examination revealed the encapsulated tumor as an anaplastic ependymoma. Almost
      complete neurologic recovery was obtained. CONCLUSION: The encapsulated
      appearance, lack of an apparent attachment to the central nervous system, and
      absence of signs of the primary neoplastic process within the brain or spinal
      cord suggested that the tumor arose from ectopic ependymal cells.

PMID- 8578383
TI  - Lumbar zygapophysial (facet) joint injections.
AB  - The lumbar zygapophysial joints are a potential cause of back and lower extremity
      pain. Absolute diagnosis of lumbar zygapophysial joint-mediated pain is based on
      selective analgesic injections of these joints or their nerve supply. The
      therapeutic role of zygapophysial joint injections is controversial. This
      contemporary concepts paper reviews the anatomy, mechanics, pathology, and
      diagnosis of this condition. A critical review of previous studies assessing the
      role of diagnostic and potentially therapeutic zygapophysial joint injection
      procedures is presented. The need for future studies is addressed, and current
      recommendations for the role of zygapophysial joint injection procedures based on
      this critical scientific review are provided.

PMID- 8578384
TI  - Lumbar discography. Position statement from the North American Spine Society
      Diagnostic and Therapeutic Committee.
AB  - STUDY DESIGN: A comprehensive review of the literature dealing with lumbar
      discography was conducted. OBJECTIVE: The purpose of the review was to generate a
      position statement addressing criticisms of lumbar discography, identify
      indications for its use, and describe a technique for its performance. SUMMARY OF
      BACKGROUND DATA: Lumbar discography remains a controversial diagnostic procedure.
      There are concerns about its safety and clinical value, although others support
      its use in specific applications. METHODS: Articles dealing with lumbar
      discography were reviewed and summarized in this report. RESULTS: Most of the
      recent literature supports the use of discography in select patients. Although
      not to be taken lightly, many of the serious and high complication rates were
      reported before 1970 and have decreased since because of improvement in injection
      technique, imaging, and contrast materials. CONCLUSIONS: Most of the current
      literature supports the use of discography in select situations. Particular
      applications include patients with persistent pain in whom disc abnormality is
      suspect, but noninvasive tests have not provided sufficient diagnostic
      information or the images need to be correlated with clinical symptoms. Another
      application is assessment of discs in patients in whom fusion is being
      considered. Discography's role in such cases is to determine if discs within the
      proposed fusion segment are symptomatic and if the adjacent discs are normal.
      Discography appears to be helpful in patients who have previously undergone
      surgery but continue to experience significant pain. In such cases, it can be
      used to differentiate between postoperative scar and recurrent disc herniation
      and to investigate the condition of a disc within, or adjacent to, a fused spinal
      segment to better delineate the source of symptoms. When minimally invasive
      discectomy is being considered, discography can be used to confirm a contained
      disc herniation, which is generally an indication for such surgical procedures.
      Lumbar discography should be performed by those well experienced with the
      procedure and in sterile conditions with a double needle technique and
      fluoroscopic imaging for proper needle placement. Information assessed and
      recorded should include the volume of contrast injected, pain response with
      particular emphasis on its location and similarity to clinical symptoms, and the
      pattern of dye distribution. Frequently, discography is followed by axial
      computed tomography scanning to obtain more information about the condition of
      the disc.

PMID- 8578385
TI  - Spine rehabilitation. Secondary and tertiary nonoperative care.
AB  - To achieve desirable behavioral outcomes, physicians treating spinal pain
      patients should be aware of appropriate algorithms for conservative care. Lower
      cost secondary rehabilitation can be effective if deconditioning, severity of
      physical symptoms, surgical equivocation, or psychosocial barriers to recovery
      are not present. Patients who have extended disability in excess of 6 months,
      recognized psychosocial barriers (depression, substance abuse, personality
      disorders, secondary gain), or severe deconditioning have a better prognosis with
      tertiary care.

PMID- 8578386
TI  - Herniated cervical intervertebral discs spontaneously produce matrix
      metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2.
AB  - STUDY DESIGN: Herniated cervical disc specimens were obtained from patients
      undergoing surgical discectomy for persistent radiculopathy and cultured in vitro
      to determine whether various biochemical agents were being produced. OBJECTIVES:
      Our hypothesis is that biochemical mediators of inflammation and tissue
      degradation play a role in cervical intervertebral disc degeneration and in the
      pathophysiology of cervical radiculopathy. SUMMARY OF BACKGROUND DATA: Neck pain
      with or without radiculopathy is a common clinical problem, but the etiology of
      neck pain and the exact pathophysiology of radiculopathy remain uncertain. We
      have previously reported the production of various biochemical agents by
      herniated lumbar disc specimens in vitro. Because of a lack of such studies in
      the literature with respect to the cervical spine, the purpose of this study was
      to determine whether similar biochemical agents of inflammation and tissue
      degradation were being produced by herniated cervical disc specimens. METHODS:
      Eighteen herniated cervical discs were obtained from 15 patients undergoing
      anterior disc surgery. The specimens were cultured and incubated for 72 hours,
      and the media were subsequently collected for biochemical analysis. Biochemical
      assays for matrix metalloproteinases, nitric oxide, prostaglandin E2, and a
      variety of cytokines were performed. As a control group, six cervical discs
      specimens were obtained from three patients undergoing anterior surgery for
      traumatic burst fractures, and similar biochemical analyses were performed.
      RESULTS: The culture media from the herniated cervical disc specimens showed
      increased levels of matrix metalloproteinase activity compared with the control
      discs. Similarly, the levels of nitric oxide, prostaglandin E2, and interleukin-6
      were significantly higher in the herniated disc specimens compared with the
      control discs. Interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor
      alpha, interleukin-1 receptor antagonist protein, and substance P were not
      detected in the culture media of the herniated or control discs. CONCLUSIONS:
      Herniated cervical disc specimens were making spontaneously increased amounts of
      matrix metalloproteinases, nitric oxide, prostaglandin E2, and interleukin-6.
      These results were similar to those obtained in herniated lumbar disc specimens
      that we have previously reported. These products may be intimately involved in
      the biochemistry of disc degeneration and the pathophysiology of radiculopathy.

PMID- 8578387
TI  - Responses of mechanosensitive afferents to manipulation of the lumbar facet in
      the cat.
AB  - STUDY DESIGN: The response of mechanosensitive afferent nerve endings in the
      lumbar spine to manipulation of a lumbar facet isolated using a unique surgical
      approach was studied in anesthetized adult cats. OBJECTIVES: To characterize
      sensory nerve endings in the lumbar spine with respect to their receptive field
      and conduction velocity and to assess their response to facet joint motion.
      SUMMARY OF BACKGROUND DATA: Previous studies have identified the presence of
      encapsulated endings in normal human facet capsules and have documented the
      presence of mechanosensitive units responsive to spinal loading. Previous
      neurophysiologic studies have used preparations that stripped all paraspinous
      musculature away from the field to expose the facets and lamina. METHODS: A
      unique hemilaminectomy approach was developed that permitted physiologic loading
      of the lumbar facet without disturbing its overlying musculature. Recordings of
      single unit afferent activity were made from fine filaments teased from the L6
      dorsal root. Response to L5-L6 facet motion was studied by applying cranial,
      craniomedial, and medial distractive forces and lateral compressive forces to the
      facet joint. RESULTS: Single unit recordings were obtained from 16 afferents with
      receptive fields in the lumbar spine. Seven of 16 afferents had receptive fields
      in or near the facet, and the remaining nine afferents had receptive fields in
      paraspinal tissues some distance from the facet joint. There were nine Group II
      afferents, three Group IV, and four unclassified afferents. The majority of
      endings responded in a graded fashion relative to the direction of force applied.
      CONCLUSIONS: Mechanosensitive endings in the lumbar spine show graded sensitivity
      to the direction of facet manipulation. These Group III and IV afferents can
      reside some distance from the facet joint and remain sensitive to facet motion.

PMID- 8578388
TI  - A model for acute, chronic, and delayed graded compression of the dog cauda
      equina. Neurophysiologic and histologic changes induced by acute, graded
      compression.
AB  - STUDY DESIGN: The results of acute compression on nerve function and morphology
      were analyzed in a recently developed model for graded cauda equina compression
      in the dog. OBJECTIVES: The model was developed to better mimic the clinical
      situation of cauda equina compression in association with spinal canal stenosis.
      SUMMARY OF BACKGROUND DATA: The compression of the cauda equina has been induced
      by metal clips, plastic bands, constrictors, and inflatable balloons. No model
      has used the intact spinal canal and induced compression by increasing the
      pressure per se in the canal. METHODS: An inflatable balloon with a diameter
      exceeding the diameter of the spinal canal was placed under the lamina of the L7
      vertebra in the dog. The balloon was inflated to various pressures, and muscle
      action potential area and nerve conduction velocity were monitored during 2 hours
      of compression and 1.5 hours of recovery. Nerve root specimens were processed for
      light microscopic examination. RESULTS: There was a progressive reduction of
      muscle action potential area and nerve conduction velocity that was proportional
      to the applied pressure. Histologic evaluation revealed no nerve fiber damage but
      a slight intraneural edema after compression at 200 mg Hg. CONCLUSIONS: The
      presented model may provide reproducible results regarding neurophysiologic and
      morphologic effects after acute, graded compression of the dog cauda equina. Two
      additional conclusions can be made from this study. First, the area measurement
      of the MAP is probably well suited for recordings and analyses of changes in
      muscle action potentials. Second, the specific onset rate of this study, in
      relation to previous studies, indicates that there is a threshold for the
      compression onset rate for inducing additional nerve injury located in the
      interval 0.1-0.8 seconds. The results from the present study provides important
      baseline data for the continued studies on chronic and intermittent compression
      with the compression model.

PMID- 8578389
TI  - Biomechanical alterations induced by multilevel cervical laminectomy.
AB  - STUDY DESIGN: The biomechanical responses of the cervical spine undergoing a
      combined loading vector within the physiologic range and after multilevel
      laminectomy were evaluated. The experimental conditions were designed to more
      closely replicate the typical clinical situation than accomplished by previous
      studies. OBJECTIVE: To determine the biomechanical alterations induced by
      multilevel cervical spine laminectomy using an in vitro model. SUMMARY OF
      BACKGROUND DATA: The few previous laboratory studies concerned with the effects
      of cervical laminectomy have generally indicated a lack of significant change in
      strength or flexibility induced by the procedure. These studies have been limited
      by a variety of factors, including the use of pure loads under low physiologic
      loading conditions, restriction of the laminectomy to one or two segments, and
      the evaluation of a small number of specimens. METHODS: Twelve fresh human
      cadaver cervical spine segments from C2-T1 were used. A custom-designed fixture
      was attached to the proximal end of the specimen to apply a flexion-compression
      load. Retroreflective targets were positioned in bony landmarks for localized
      temporal kinematics of the entire cervical column. Testing was performed before
      (intact) and after a three-level (C4-C6) laminectomy, and data regarding the
      force, displacement, and kinematics at every level of the column were obtained.
      RESULTS: The mean stiffness of the intact cervical column was significantly
      greater (P < 0.05) than the mean stiffness for the laminectomized specimen.
      Sagittal rotation angle had significant (P < 0.05) differences between intact
      (3.6 degrees) and laminectomy (8.0 degrees). Laminectomized specimens
      consistently responded with higher rotations compared with the intact specimen at
      every cervical spine level. CONCLUSION: Multilevel cervical laminectomy induces
      significant increases in total column flexibility associated with increased
      segmental flexural sagittal rotations. These motion changes were generalized with
      a tendency to show the greatest change at the lower level of laminectomy. Such
      biomechanical changes may constitute part of the underlying basis for failure of
      laminectomy to offer sustained good therapeutic results of the myelopathy
      associated with cervical stenosis and cervical spondyloarthropathy.

PMID- 8578390
TI  - Effect of spinal construct stiffness on short segment fusion mass incorporation.
AB  - STUDY DESIGN: Three segment (L3-L5) pedicle screw constructs were implanted in
      caprine spines, and the resulting ankylosis evaluated mechanically and compared
      12 weeks after surgery. OBJECTIVES: To determine if a construct of maximal
      stiffness could impair the biologic process of spinal arthrodesis by "stress
      shielding." SUMMARY OF BACKGROUND DATA: Fusion mass stiffness is believed to be
      enhanced by increasing construct stiffness, although previous studies have used
      semirigid, nonconstrained constructs, which lose stiffness through cyclical
      loading. Device-related osteoporosis, reported to occur with stiff, constrained
      implants, may be more related to the presence of fusion induced by the implants
      rather than the implants themselves. METHODS: In 15 goats, L3-L5 segments were
      instrumented with pedicle screws, and four different diameters of rods (3.2 cm,
      4.8 cm, 6.4 mm, and no rods) were implanted as longitudinal connections to vary
      the stiffness of the constructs. After 12 weeks, animals were killed and the
      segments were tested to determine their stiffness. RESULTS: In lateral bending,
      spines "fused" with rods (any size) were significantly stiffer (P = 0.03) than
      nonrodded spines. There was a trend toward stiffer segments with larger rods (4.8
      cm or 6.4 mm) compared with 3.2 mm or no rods. There was a highly significant (P
      < 0.0001) increase in stiffness of all operated (rodded or nonrodded) segments
      compared with unoperated controls. CONCLUSIONS: The enhancement of segmental
      stiffness by stiffer constructs was confirmed, suggesting a beneficial effect on
      spinal arthrodesis by increasing stiffness. Stress shielding could not be shown.

PMID- 8578391
TI  - Biomechanical properties of threaded inserts for lumbar interbody spinal fusion.
AB  - STUDY DESIGN: Calf and human cadaveric spines were used to determine motion
      segment stiffness and laxity after implantation of threaded inserts (the Ray
      Threaded Fusion Cage, Surgical Dynamics, Inc., Concord, CA), comparing direction
      of placement, number of implants, shape of the device, and integrity of anterior
      spine structures. Stiffness and laxity of spines with inserts were compared with
      those with bone grafts, with and without posterior fixation plates. OBJECTIVES:
      To determine the mechanical stabilizing properties of a threaded insert used for
      lumbar and lumbosacral fusion and the factors affecting stability. SUMMARY OF
      BACKGROUND DATA: Limited biomechanical information has shown that implantation of
      these devices adds stiffness to the lumbar spine, but little information is
      available concerning stiffness in loading directions other than flexion and
      extension, the effect on stiffness of position and number of implants, and the
      effect of this device on motion segment laxity. METHODS: Mechanical properties
      were determined by testing lumbar vertebral motion segments in flexion,
      extension, lateral bending, and torsion combined with axial compressive loading.
      Stiffness (slope of the load/deflection curve) and neutral zone angle or laxity
      (angular displacement of the vertebra from no load to 1.0 Nm moment) were
      determined. Initial tests were performed on calf lumbar vertebrae to determine
      the effects of placement and number of inserts. Comparisons of bone grafts and
      inserts with and without supplemental plates were made using human lumbar spines.
      Cylindrical- and conical-shaped inserts, when placed from anterior, were tested
      in calf spines. The load-bearing capacity of the insert supported in calf
      vertebral body bone was determined. RESULTS: There was no significant effect of
      placement of inserts in different orientations (lateral, posterolateral, or
      posterior) on stiffness, except in torsion where posterior placement damaged
      facets or lamina, reducing stiffness. Placement of two inserts from posterior
      decreased flexion and lateral bending laxity compared with the intact motion
      segment. Compared with intact, bone grafts produced more stiffness only in
      lateral bending and had no effect on laxity. Supplemental posterior plates fixed
      by pedicle screws across the fusion segment increased flexion and lateral bending
      stiffness and reduced laxity in flexion, extension, and lateral bending. Conical
      shaped inserts placed from anterior into cylindrical holes distracted soft tissue
      structures, decreasing laxity. Cutting the anterior structures increased laxity
      by relieving some tissue tension caused by distraction. The mean maximum
      compressive load that could be supported by the insert was 2998 N (standard
      deviation = 980 N). Structural failure occurred in the supporting bone.
      CONCLUSIONS: Threaded inserts increase vertebral motion segment stiffness and
      decrease laxity by distracting intervertebral structures. They are not sensitive
      to placement, except if vertebral structures are injured during insertion and
      produce constructs with more consistent mechanical properties than bone grafts.

PMID- 8578392
TI  - Relation of spinal and thoracic cage deformities and their flexibilities with
      altered pulmonary functions in adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Seventy patients (average age, 13.8 years) with adolescent
      idiopathic right thoracic scoliosis had full assessment of pulmonary functions
      and radiographic evaluation of spinal and thoracic cage deformities and their
      flexibilities. OBJECTIVES: To determine how measurements of spinal and thoracic
      cage deformities related to pulmonary function. SUMMARY OF BACKGROUND DATA:
      Pulmonary functions have been evaluated in relation to lateral curvature of the
      spine in most of the published studies. Scoliosis is a three-dimensional
      deformity. There is a need to evaluate these changes in pulmonary functions,
      reflecting not only spinal curvature but also rotational deformity, thoracic cage
      deformity, and their flexibilities. METHODS: Radiographic measurements obtained
      from anteroposterior and lateral standing and anteroposterior supine bending
      radiographs included lateral curvature, vertebral rotation, kyphosis, maximum
      sternovertebral distance, and apical rib-vertebral angles. Using previous
      measurements, the flexibility of the curve, vertebral rotation, and rib-vertebral
      angle were calculated. A pulmonary function assessment was performed using a
      computerized pulmonary function system (5000V; Gould, Dayton, Ohio). We analyzed
      pulmonary functions in relation to deformity. RESULTS: Measurements reflecting
      spinal deformities obtained from anteroposterior radiographs, such as Cobb angle,
      vertebral rotation, and vertebral rotation flexibility, were significantly
      correlated with the percent of predicted values of vital capacity and forced
      vital capacity, whereas kyphosis measured from lateral radiographs was
      significantly correlated with absolute values of residual volume, total lung
      capacity, functional residual capacity, and forced expiratory flow from 25-75% of
      the forced vital capacity (FEF25-75). Of the measurements reflecting thoracic
      cage deformity obtained from anteroposterior radiographs, rib-vertebral angle
      asymmetry (measured from supine bending radiographs) showed significant
      correlation with the percent of predicted values of vital capacity, forced vital
      capacity, and functional residual capacity, whereas the sternovertebral distance
      that was measured from lateral radiographs correlated significantly with absolute
      values of vital capacity, total lung capacity, forced vital capacity, and FEF25
      75. CONCLUSIONS: Deformities in coronal and transverse plane influence changes in
      pulmonary functions expressed as the percent of predicted values, whereas
      sagittal plane deformities influence mainly those absolute volumes in which
      residual volume is a component. It is suggested that rotational flexibility
      combined with other deformities could be evaluated in future studies on
      prediction of pulmonary function from the measurements of the deformity.

PMID- 8578393
TI  - Motion characteristics of the lumbar spine in the normal population.
AB  - STUDY DESIGN: The present study investigated the dynamic motion characteristics
      of the lumbar spine in the normal population using a potentiometric analysis
      system. OBJECTIVES: To assess the ability of a triaxial potentiometric analysis
      system to measure dynamic motion in the lumbar spine, and to use this system to
      form a database of dynamic motion characteristics from which normal parameters of
      motion and the factors affecting this motion could be defined. SUMMARY OF
      BACKGROUND DATA: Spinal motion has been studied using a variety of different
      methods, the majority of which have been limited either in terms of reliability,
      accuracy, or invasiveness and many have been only of a static nature. There has
      been no previous study into the normal dynamic motion characteristics of the
      lumbar spine. METHODS: The accuracy of the system was determined by a series of
      tests against a calibrated engineering mill, and the reliability of the system
      was assessed on 10 subjects with repeated measurements over a 3-day period.
      Values of range of motion and angular velocity were obtained from 203 normal
      subjects during flexion and extension, lateral flexion, and rotation. RESULTS:
      The results of the calibration testing revealed excellent accuracy, and it was
      shown that the system was repeatable. Initial analysis of the results indicated
      that sex differences did exist with men having 58.4 degrees of flexion and women
      having 53.4 degrees. Age appeared to have an influence on motion, and a gradual
      reduction was seen with each decade (P < 0.001), with the 20-29-year age range
      having 59.5 degrees mean flexion, the 30-39-year group having 58.1 degrees, the
      40-49-year group having 53.7 degrees, the 50-60-year group having 57.5 degrees,
      and the 60-70-year group having 45.9 degrees. Multiple regression techniques
      revealed that only a few factors are important with respect to motion and that
      these varied according to the characteristic being defined. CONCLUSIONS: Range of
      motion tended to be affected by age and sex, whereas velocity was only affected
      by distance moved, with occupation and body mass index having little or no
      influence on the motion. The factors identified could only account for a small
      proportion of the variation seen, suggesting that it is difficult to predict the
      motion characteristics with any degree of sensitivity.

PMID- 8578394
TI  - Spinal cord monitoring of the ventral funiculus function. Analysis of spinal
      field potentials after galvanic vestibular stimulation.
AB  - STUDY DESIGN: This study was designed to examine the possibility of a new spinal
      cord monitoring method using galvanic vestibular stimulation to monitor the
      function of the ventral funiculus of the spinal cord. OBJECTIVES: To settle the
      problems of previous monitoring methods by using galvanic vestibular nerve
      stimulation, which is highly selective for monitoring the function of the ventral
      funiculus of the spinal cord. SUMMARY OF BACKGROUND DATA: Although various spinal
      cord monitoring methods have been used, there are still problems because
      potentials recorded by these methods do not reflect selectively the function of
      the ventral funiculus of the spinal cord, which is vulnerable during anterior
      spinal surgeries. METHODS: In anesthetized cats, field potentials evoked by
      galvanic stimulation of the labyrinth were recorded from the epidural space of
      the spinal cord. The origin of these potentials was determined by mapping field
      potentials from within the upper cervical spinal cord using a micropipette and by
      examining the effect of sectioning the brainstem on the evoked potentials.
      RESULTS: The spinal cord potentials evoked by galvanic stimulation between the
      bilateral labyrinths could be recorded from the epidural space, and these
      potentials mainly originated from the ventral and ventromedial funiculus of the
      spinal cord. The latency and intraspinal distribution of the evoked potentials
      and the effect of sectioning the medial longitudinal fascicle on the evoked
      potentials indicated that the earliest component of the evoked potentials
      reflects mainly the activity of the vestibulospinal tract. CONCLUSIONS: Recording
      spinal cord potentials evoked by galvanic vestibular stimulation from the
      epidural space appears to be a potential technique to monitor the functional
      state of the ventral funiculus during anterior spinal surgeries.

PMID- 8578395
TI  - Surgical revision for failed anterior cervical fusions. Articular pillar plating
      or anterior revision?
AB  - STUDY DESIGN: This retrospective study reviewed one surgeon's experience in
      treating symptomatic anterior cervical pseudarthrosis by three methods: anterior
      revisions, posterior revisions, and circumferential procedures. OBJECTIVES: To
      determine whether anterior revision and plating achieves a higher probability of
      radiographic fusion and better clinical outcomes compared with posterior fusion
      and articular pillar plating. The role of circumferential procedures was
      evaluated. SUMMARY OF BACKGROUND DATA: Management of cervical pseudarthrosis by a
      repeat anterior procedure requires a difficult dissection in a previously
      operated area, resection of a nonunion site, and regrafting. Because the
      incidence of failure is reported to be high, posterior cervical fusion has been
      proposed as a treatment for anterior pseudarthrosis. METHODS: The second author
      has performed 44 surgical revisions for symptomatic anterior cervical
      pseudarthrosis. Before this surgical revision, all patients had pain and a
      radiographic nonunion that was confirmed during surgery. The average follow-up
      period after the secondary procedure was 28 months with a range of 12-60 months.
      All patients (100%) were available for follow-up evaluation. Twenty patients had
      anterior pseudarthrosis repair and anterior plating. Seventeen patients underwent
      posterior cervical fusion and articular pillar plating. Seven patients had a
      circumferential repair with anterior revision and posterior articular pillar
      plating. RESULTS: All seven patients (100%) who had circumferential procedures
      achieved a solid radiographic fusion. Clinically, five patients felt better than
      before surgery, and two patients felt the same. Sixteen of 17 patients (94%) with
      posterior repairs achieved a solid fusion. Fourteen patients felt better; two
      patients felt the same, and one patient with a nonunion felt worse than before
      surgery. A solid fusion was obtained in only 45% of the patients after anterior
      repair alone. CONCLUSIONS: Posterior cervical articular pillar plating and fusion
      result in a higher probability of fusion than repeat anterior procedures, even
      with the addition of anterior plate stabilization. Posterior fusion and articular
      pillar plating, whether alone or part of a circumferential procedure, provides
      the added fixation required to successfully repair failed anterior cervical
      fusions.

PMID- 8578396
TI  - Complications of posterior cervical plating.
AB  - STUDY DESIGN: This retrospective clinical study evaluates complications occurring
      during or immediately after surgery of posterior cervical plating. OBJECTIVES:
      The present study quantifies risks associated with posterior cervical plating
      using lateral mass screw fixation. The observed clinical complications are
      compared with theoretical risks previously studied in cadavers. Unanticipated
      complications are identified. SUMMARY OF BACKGROUND DATA: There are many reports
      that describe posterior cervical plating and attempt to describe the indications
      for using this type of fixation, but few studies have discussed the clinical
      complications incurred by application of these plates and screws. METHODS:
      Seventy-eight consecutive patients whose treatment included posterior cervical
      lateral mass plating were independently reviewed to identify associated
      complications. The average patient age was 52.9 years, and the average follow-up
      period was 2 years (range, 10-47 months). Multiple indications for surgery were
      present, but complex reconstructive procedures were required in 70.5% of cases.
      Complication rates were calculated as either a percentage of the number of screws
      inserted or as a percentage of the number of cases performed or both. RESULTS:
      Six hundred fifty-four screws were inserted--an average of 8.4 screws per
      patient. Complication rates as a function of the number of screws inserted
      included nerve root injury, 0.6%; facet violations, 0.2%; vertebral artery
      injury, 0%; broken screw, 0.3%; screw avulsion, 0.2%; and screw loosening 1.1%.
      Complications as a percentage of the number of cases performed included spinal
      cord injury, 2.6%; iatrogenic foraminal stenosis, 2.6%; broken plate, 1.3%; lost
      reduction, 2.6%; adjacent segment degeneration, 3.8%; infection, 1.3%; and
      pseudoarthrosis, 1.4%. CONCLUSIONS: Cadaveric work has predicted certain anatomic
      complication rates associated with lateral mass screw insertion. This study finds
      the risk of lateral mass screw insertion to be considerably less than predicted
      in vitro. The present study reports other complications that were not predicted
      in laboratory studies.

PMID- 8578397
TI  - Occurrence of infection in anterior cervical fusion for spinal cord injury after
      tracheostomy.
AB  - STUDY DESIGN: This study retrospectively reviewed the outcomes of 11 patients
      treated for a cervical spine injury with a tracheostomy placed before anterior
      cervical spine surgery. OBJECTIVES: The primary goal was to show that anterior
      cervical spine surgery in the setting of spinal cord injury is a viable option in
      patients with previous tracheostomy. SUMMARY OF BACKGROUND DATA: Respiratory
      failure after cervical cord injury commonly requires tracheostomy, possibly
      increasing the risk of soft tissue or bony infection in patients at high risk for
      morbidity after surgery. Although numerous studies have explored the risk of
      infection after tracheostomy or anterior cervical spine surgery, no study has
      been performed to explore the risk of infection in patients with previous
      tracheostomy at the time of anterior cervical spine surgery. METHODS: A
      retrospective review of the clinical data of 1800 spinal cord injury patients
      seen from 1979 to the present at the Regional Spinal Cord Injury Center of the
      Delaware Valley of Thomas Jefferson University with affiliated institutions of
      Thomas Jefferson University Hospital and Magee Rehabilitation Hospital was
      performed. Eleven patients were found who had existing tracheostomy at the time
      of anterior cervical spine surgery. Clinical follow-up period averaged 28 months
      with a range of 6-51 months, and radiographic analysis averaged 7 months with a
      range of 1-51 months. Autogenous iliac crest graft was used in all patients,
      consisting of an intervertebral graft after a discectomy or a strut graft after a
      complete corpectomy. Anterior instrumentation was used in more than 50% of the
      patients. RESULTS: After all patient interviews and review of all radiographs for
      evidence of infection, no patient was noted to have evidence of a cervical soft
      tissue or bony infection after surgery. The tracheostomy complications were minor
      and resolved quickly. CONCLUSIONS: The authors concluded that in patients with
      cervical cord damage resulting from nonpenetrating trauma, tracheostomy was not
      found to increase the risk of infection in subsequent anterior cervical surgery.
      Careful preparation of the skin and placement of the second surgical incision
      lateral to the tracheostomy site is recommended. Anterior cervical spine surgery
      remains a viable treatment option in this severely injured patient population.

PMID- 8578398
TI  - Vertebral body replacement with a ceramic prosthesis for metastatic spinal
      tumors.
AB  - STUDY DESIGN: This study retrospectively analyzed the clinical outcome of
      vertebral replacement surgery with our unique ceramic prosthesis for spinal
      metastases. OBJECTIVES: To indicate the results of vertebral replacement surgery
      with a ceramic prosthesis. SUMMARY OF BACKGROUND DATA: Spinal metastasis often
      involves the vertebral bodies, of which abnormal fracture causes intractable pain
      and paresis. For such conditions, laminectomy or irradiation can have no effect
      because they do not improve spinal stability. Autogenous bone or bone cement are
      not durable materials, and fatigue fracture of the implanted material
      occasionally occurs. We developed a simple prosthesis made of alumina ceramic, a
      bioinert material, to replace the affected vertebrae. There has not been such a
      large study to assess vertebral replacement surgery with a ceramic prosthesis.
      METHODS: From 1972 to 1993, 90 ceramic prostheses were used in 84 patients with
      spinal metastasis, and the average follow-up period was 26.2 months. The primary
      tumor was thyroid cancer in 13 patients, breast cancer in 12, multiple myeloma in
      eight, renal cell cancer in eight, gastrointestinal cancer in eight, and lung
      cancer in eight. The clinical symptoms were assessed before and after surgery,
      and the maintenance of operative gain was investigated. RESULTS: Pain relief was
      achieved in 94%, motor function improved in 81%, and ambulation recovered in 64%.
      There were no serious complications associated with the procedure, and the
      operative benefit was maintained until the terminal stage in the vast majority of
      patients. CONCLUSIONS: In selected patients, vertebral replacement using our
      prosthesis proved to be a useful procedure, effectively managing the severe
      spinal pain or neurologic deficits associated with vertebral body destruction.

PMID- 8578399
TI  - Nucleus pulposus pulmonary embolism. A case report.
AB  - STUDY DESIGN: This postmortem case report describes nucleus pulposus pulmonary
      embolism occurring in a human. OBJECTIVES: Clinical, pathologic, and pathogenetic
      features of the case are discussed. Reference is made to warnings in the
      literature stressing the importance of avoiding, during radiologic procedures,
      any possibility of intrathecal ingress of iodinated, ionic, hyperosmolar contrast
      material. SUMMARY OF BACKGROUND DATA: Various tissues have been implicated as
      pulmonary emboli in humans. Nucleus pulposus has been reported to embolize to
      spinal cord vessels in animals and humans and to embolize to the lungs in two
      animal species. This is the first report of nucleus pulposus pulmonary embolism
      in a human. METHODS: A patient with refractory low back pain was admitted for
      lumbar discography using diatrizoate meglumine, 52%, and diatrizoate sodium, 8%.
      Afterward, an ultimately fatal systemic reaction began, among the symptoms of
      which were spasmodic extensions of the lower back and legs. Postmortem
      examination was performed. RESULTS: Nucleus pulposus pulmonary emboli were seen
      microscopically on random lung sections. The lumbar vertebral column grossly
      featured acute herniations of disc material into vertebral marrow spaces; nucleus
      pulposus was identified microscopically in these areas. CONCLUSIONS: We speculate
      that the spasmodic back extensions imposed compressive forces on vertebrae,
      causing nucleus pulposus to be extruded into vertebral marrow sinusoids (thus
      creating emboli) and possibly causing these emboli to flow anteriorly into the
      anterior external vertebral plexus, which resulted in pulmonary emboli
      exclusively with no spinal cord emboli.

PMID- 8578400
TI  - A complication of spinal decompression. A case report.
AB  - STUDY DESIGN: This case study is designed to report the previously unreported
      specific complication of acute cauda equina compression after decompression
      surgery for spinal stenosis. OBJECTIVES: To inform others of the possibility of
      such a complication; to suggest a possible mechanism for this situation, namely
      hourglass constriction of the cauda causing ischemia to distal nerve roots; and
      to suggest a management plan--immediate magnetic resonance imaging to identify
      the problem and return to the operating room for further decompression--which was
      successful in this case. SUMMARY OF BACKGROUND DATA: Previous reports of causes
      of paraparesis or paraplegia after surgery are listed, and previous theories on
      the etiology of acute cauda compression are discussed. METHODS: The clinical
      findings of spinal stenosis in a 32-year-old man are presented, and subsequent
      details of the surgery, complications after surgery, investigation, and future
      surgery, including magnetic resonance imaging scans before and after surgery, are
      provided. RESULTS: The result in this case was a patient free of symptoms.
      CONCLUSIONS: Incomplete decompression in surgery for spinal stenosis can result
      in acute cauda equina compression. In these circumstances, magnetic resonance
      imaging can reveal the cause, and in this case, immediate surgery was successful
      in relieving the symptoms and signs.

PMID- 8578401
TI  - Extensive epidural hemangioma with skin and bone involvement. A case report.
AB  - STUDY DESIGN: This is a case report. OBJECTIVE: To report and to examine the
      clinical findings and management of epidural cavernous hemangioma. SUMMARY OF
      BACKGROUND DATA: Spinal epidural cavernous hemangiomatous malformation is a very
      rare entity. Only 20 cases of this disease have been reported in the literature.
      METHODS: The case of a 20-year-old woman with spinal epidural cavernous
      hemangioma was reviewed. RESULTS: The clinical presentation, diagnosis, and
      therapy of this disease are discussed. CONCLUSION: The treatment of epidural
      hemangioma consists of total or subtotal excision of the lesion, depending on the
      relation of the lesion to the spinal cord.

PMID- 8578402
TI  - Chlamydia trachomatis infection among Hispanic women in the California-Mexico
      border area, 1993: establishing screening criteria in a primary care setting.
AB  - BACKGROUND: Chlamydia prevalence and transmission patterns in California-Mexico
      border communities are unknown, and selective screening strategies for Hispanic
      populations have not been evaluated. GOAL OF THIS STUDY: To determine chlamydia
      prevalence among Hispanic women in the California-Mexico border area and
      established screening criteria. STUDY DESIGN: This was a cross-sectional
      prevalence survey of family planning/prenatal Hispanic clients (n = 2378) in San
      Diego and Imperial Counties, California, and Tijuana, Mexico. RESULTS: Overall,
      chlamydia prevalence was 3.2% (3.3% in California; 2.1% in Mexico). Women born in
      Mexico or those who visited Mexico for at least 1 week in the recent past had a
      prevalence rate similar to women without those characteristics. Multivariate
      analysis showed that young age (less than 25 years old), unmarried status, or
      having clinical signs of a chlamydia syndrome (primarily cervicitis) or vaginosis
      independently predicted chlamydia infection. Applying minimum screening criteria
      recommended by the Centers for Disease Control would require screening less than
      half of the clients. However, only 69% of infections would be identified. Using
      survey-based criteria (less than 25 years old, unmarried, and clinical signs of a
      chlamydia syndrome) would require screening 64% of clients, but would identify
      92% of those infected. CONCLUSION: Chlamydia prevalence among Hispanic women
      seeking reproductive healthcare was similar (< 5%) on both sides of the
      California-Mexico border. Among Hispanic women, using easily obtained demographic
      data (age and marital status) and clinical signs (primarily cervicitis), an
      effective selective screening strategy can be implemented.

PMID- 8578403
TI  - Commonly used diagnostic criteria for pelvic inflammatory disease have poor
      sensitivity for plasma cell endometritis.
AB  - BACKGROUND: The majority of women with tubal damage do not have a history of
      acute pelvic inflammatory disease. The prevalence of upper genital tract
      inflammation was evaluated in women deemed not to have pelvic inflammatory
      disease by common diagnostic criteria. GOAL OF THIS STUDY: To compare clinical
      signs and laboratory tests used to diagnose pelvic inflammatory disease with
      endometrial biopsy histopathology. STUDY DESIGN: Endometrial biopsy and commonly
      used physical and laboratory tests were performed on 52 women with pelvic
      tenderness, 51 with vaginosis or cervicitis, and 22 control subjects who had no
      evidence of infection with Neisseria gonorrhoeae or Chlamydia trachomatis and who
      tested negative for bacterial vaginosis using vaginal swab Gram's stain. RESULTS:
      Thirty-six of 52 patients (69%) with pelvic tenderness, compared with 22 of 51
      patients (43%) with vaginosis or cervicitis and two of 22 control subjects (9%),
      had plasma cell endometritis. The Centers for Disease Control and Prevention
      minimal diagnostic criteria for pelvic inflammatory disease had a sensitivity of
      33% for plasma cell endometritis. CONCLUSIONS: The clinical diagnosis of pelvic
      inflammatory disease using published criteria correlates poorly with plasma cell
      endometritis.

PMID- 8578404
TI  - The semantics of pelvic inflammatory disease.

PMID- 8578405
TI  - The relationship of vaginal trichomoniasis and pelvic inflammatory disease among
      women colonized with Chlamydia trachomatis.
AB  - BACKGROUND: Trichomonas vaginalis is a common sexually transmitted pathogen that
      has been linked to upper genital tract bacterial disease. Its association with
      upper tract chlamydial disease has not been assessed. GOAL OF THIS STUDY: This
      study was undertaken to determine whether women colonized with Chlamydia
      trachomatis who are also infected with Trichomonas vaginalis are at increased
      risk for having pelvic inflammatory disease. STUDY DESIGN: A nested case control
      methodology was used to compare Trichomonas vaginalis rates between women
      colonized with Chlamydia trachomatis who had pelvic inflammatory disease (n = 24)
      and those who were colonized but did not have pelvic inflammatory disease (n =
      47). Factors that might be related to the development of upper tract disease
      (e.g., douching, other sexually transmitted diseases) and factors linked to
      colonization with Trichomonas vaginalis (e.g. race, use of oral contraceptives)
      were assessed. RESULTS: When exact logistic regression models were used and
      variables associated with pelvic inflammatory disease were considered, it was
      found that age (odds ratio = 0.73; P = .001) and Trichomonas vaginalis
      colonization (odds ratio = 4.72; P = .053) were significant. CONCLUSIONS: In this
      preliminary study of women colonized with Chlamydia trachomatis, an association
      was found between co-infection with Trichomonas vaginalis and evidence of upper
      tract disease.

PMID- 8578406
TI  - The importance of social histories for assessing sexually transmitted disease
      risk.
AB  - BACKGROUND: Although identifying risk groups for sexually transmitted diseases
      based on age or race may be useful for targeting screening efforts, clinicians
      should recognize that even members of most "low-risk" groups include some
      individuals at higher risk of infection. GOAL OF THIS STUDY: This case series of
      generally older people with sexually transmitted diseases illustrates how
      assumptions regarding age and risk group can lead to missed opportunities for
      sexually transmitted disease prevention. STUDY DESIGN: Records were compiled from
      two clusters of patients with sexually transmitted diseases seen at a
      Springfield, Mass., health center between March and September 1992. RESULTS: Nine
      patients with a sexually transmitted disease (one with syphilis/human
      immunodeficiency virus co-infection, one with herpes/human immunodeficiency virus
      co-infection, two with human immunodeficiency virus infections, and five with
      syphilis) are described. Eight of the patients are linked epidemiologically.
      CONCLUSIONS: A social history is essential during a medical encounter for
      sexually transmitted disease prevention purposes. Relying on assumptions
      regarding risk groups, as well as sexual activity, age, or other medical
      conditions, may lead to a patient's level of risk of infection going
      unrecognized. Discomfort associated with asking the sensitive questions involved
      in a social history also is a barrier to recognizing risks or infections. Non
      judgmental sexual histories are appropriate when evaluating all patients.

PMID- 8578407
TI  - The high prevalence of genital herpes among patients with genital ulcer disease
      in Uganda.
AB  - BACKGROUND: Genital ulcer disease is a risk factor for transmission of human
      immunodeficiency virus. One-hundred consecutive Ugandan patients (median age, 25
      years) with genital ulcer disease were examined to determine the prevalence of
      genital herpes and its relationship to human immunodeficiency virus
      seropositivity. GOAL OF THIS STUDY: To improve management, prevention, and
      control of genital ulcer disease, thus reducing human immunodeficiency virus
      infections attributable to genital ulcer disease. STUDY DESIGN: This was a
      prevalence study of genital herpes in a consecutive sample of an urban sexually
      transmitted disease clinic population. RESULTS: Forty-nine percent (48/98) of the
      patients had genital herpes (36% by direct fluorescent antigen and 13% by history
      of recurrent vesicles). There was a trend toward larger lesions in patients who
      were human immunodeficiency virus seropositive. Twelve percent (11/89) of
      patients had syphilis, and 30% (30/100) remained sexually active, despite the
      presence of active genital ulcer disease. Sixty-five percent of 89 patients
      tested had antibodies to human immunodeficiency virus. CONCLUSIONS: Genital
      herpes is a common cause of genital ulcer disease in patients attending sexually
      transmitted disease clinics in Uganda, and herpes ulcers may be more extensive
      among those who are infected with human immunodeficiency virus.

PMID- 8578408
TI  - The influence of sexual and social factors on the risk of Chlamydia trachomatis
      infections: a population-based serologic study.
AB  - BACKGROUND: Genital chlamydia infections often are asymptomatic, which promotes
      their spread in the population. In women, the possible consequences of infection
      are pelvic inflammatory disease and infertility. Most studies on the prevalence
      of Chlamydia trachomatis have been based on clinical series, and prevalences tend
      to vary with the clinical setting. Few seroepidemiologic studies have emerged
      from industrialized countries. GOAL OF THIS STUDY: To assess the prevalence of
      Chlamydia trachomatis using culture and serology, and its relationship with
      possible risk factors. STUDY DESIGN: This was a population-based study involving
      completion of a self-administered questionnaire, analysis of cervical samples for
      Chlamydia trachomatis, and serologic tests for Chlamydia trachomatis antibodies.
      RESULTS: The prevalence of Chlamydia trachomatis infection was 2.7%, and the
      seroprevalence was 24.7% among the sexually active women. Seropositivity was
      correlated with sexual behavior variables, and the incidence of serologic cross
      reactivity with respiratory infections (strain TWAR) was low. Multivariate
      logistic regression analysis showed the number of sexual partners, age at first
      coitus, history of therapeutic abortion, and previous pelvic inflammatory disease
      to be independently correlated with seropositivity. CONCLUSION: Early sexual
      experience and multiple lifetime sexual partners are independent risk factors for
      Chlamydia trachomatis infection.

PMID- 8578409
TI  - Congenital syphilis in Maryland, 1989-1991: the effect of changing the case
      definition and opportunities for prevention.
AB  - BACKGROUND: The reported incidence of congenital syphilis in the United States
      rose dramatically during the 1980s. Although lack of prenatal care has been
      associated with congenital syphilis, little has been published regarding missed
      opportunities for prenatal intervention. GOAL OF THIS STUDY: To determine whether
      congenital syphilis increases in Maryland between 1989 and 1991 resulted from a
      true increase in congenital syphilis incidence or a change in the surveillance
      case definition, and to describe missed opportunities for prenatal intervention.
      STUDY DESIGN: This was a retrospective cohort study. RESULTS: When the revised
      case definition was used, a 473% increase in the number of cases was seen. Among
      infants who met the revised definition, 45% of mothers had received no prenatal
      care. Among those whose mothers had received prenatal care, opportunities to
      intervene were missed for 53%. CONCLUSIONS: Although a true increase in
      congenital syphilis incidence occurred before 1990, the increase reported in
      Maryland between 1989 and 1991 was primarily due to the change in case
      definition. Many cases of congenital syphilis could have been prevented with
      early and adequate prenatal care.

PMID- 8578410
TI  - Metronidazole: utilization in the obstetric and gynecologic patient.
AB  - BACKGROUND: Obstetric and gynecologic complications associated with bacterial
      vaginosis and trichomoniasis have heightened awareness of these conditions, and
      thus metronidazole's role in obstetric and gynecologic practice continues to
      increase. GOAL OF THIS STUDY: To review the clinical indications for
      metronidazole in the obstetric and gynecologic setting, as well as the
      pharmacokinetics and potential adverse effects of the drug. STUDY DESIGN: Review
      of the current literature concerning metronidazole. RESULTS AND CONCLUSIONS:
      Metronidazole remains a valuable agent for the treatment of anaerobic and
      protozoal infections with little evidence of resistance. Although issues of
      mutagenicity and carcinogenicity remain theoretical concerns, current data do not
      support the existence of these risks in humans.

PMID- 8578411
TI  - Human immunodeficiency virus partner notification in a low incidence urban
      community.
AB  - BACKGROUND: Notification of the partners of a person newly diagnosed with human
      immunodeficiency virus (HIV) is legally mandated in Missouri. METHODS: In a four
      year period, the Kansas City Health Department tested for HIV antibodies in
      61,464 of 61,700 (99.6%) eligible persons using the sexually transmitted disease
      clinic. RESULTS: A total of 366 newly diagnosed HIV cases were identified of whom
      291 named 662 sex or needle-sharing partners. Only 447 partners could be located,
      counseled and/or tested. Of these partners, 165 were HIV infected, but only 33
      represented newly diagnosed cases. CONCLUSION: HIV partner notification can be
      successfully conducted in an urban community.

PMID- 8578412
TI  - Acute gonococcal sepsis in an HIV-infected woman.
AB  - This is a case report of a 35-year-old woman infected with the human
      immunodeficiency virus who presented with acute bacterial sepsis that proved to
      be secondary to Neisseria gonorrhoeae. Typical skin and joint findings developed
      only after the acute sepsis had resolved. Patients with disseminated gonococcal
      infection rarely have signs of acute bacterial sepsis. This case raises the
      question of whether HIV-infected patients are at an increased risk of contracting
      severe gonococcal disease.

PMID- 8578413
TI  - Prevalence of genital Chlamydia trachomatis infection in selected populations in
      China.
AB  - BACKGROUND: Chlamydia trachomatis is an important pathogen of the urogenital
      tract. Numerous epidemiologic studies have reported on the prevalence of
      chlamydia world wide. However, the prevalence of Chlamydia trachomatis in China
      has not been widely studied. GOAL OF THIS STUDY: To identify Chlamydia
      trachomatis in three distinct populations in China. Urogenital specimens were
      collected from men with no prior history of sexual intercourse (virgin), men seen
      at a sexually transmitted disease clinic, and female prostitutes. STUDY DESIGN:
      Two-hundred urethral swabs were collected from group one, and 100 urethral swabs
      from group two, and 109 cervical swabs from group three. All specimens were
      tested for chlamydia by tissue culture isolation using McCoy cells and an iodine
      stain. RESULTS: Chlamydia trachomatis was not isolated from the virgin males. The
      prevalence of chlamydia in men seen at a sexually transmitted disease clinic was
      13% (13/100) and in female prostitutes, 37.6% (41/109). CONCLUSION: The
      prevalence of chlamydia seen in these three groups is similar to rates found in
      previous studies done in the United States and Europe in similar populations.
      Patients with multiple sex partners in China need to be screened for C.
      trachomatis.

PMID- 8578414
TI  - Chancroid detected by polymerase chain reaction--Jackson, Mississippi, 1994-1995.

PMID- 8578415
TI  - Impact of occupational hearing loss on the lives of workers.

PMID- 8578416
TI  - Biologic bases of noise-induced hearing loss.
AB  - The effects of noise are pervasive, and pathology can be found in the neural,
      sensory, supporting, and vascular cells of the cochlea after certain noise
      exposures. Several issues need to be addressed. First, what is the source of the
      wide range of susceptibility seen in people and animals that have similar noise
      histories but markedly different response to noise? Does this suggest a genetic
      factor in susceptibility to NIHL? Second, given the complexity of the biologic
      changes following noise exposures, it is difficult to predict the underlying
      pathology from standard audiologic tests. However, it would be desirable to
      distinguish sensory and neural and strial pathology because it is likely that the
      success of any aural rehabilitation will depend on knowledge of the type of
      pathology. This chapter focuses on a number of the traditional issues surrounding
      NIHL. However, one of the most exciting recent findings that undoubtedly will
      affect people with NIHL is that it is possible for sensory cells to regenerate.
      Research into the fundamental biochemical processes responsible for inducing
      regeneration is being pursued at a number of laboratories. The hope is to be able
      to repopulate the mammalian sensory epithelium with viable sensory cells.

PMID- 8578417
TI  - Use of animal models in the study of the effects of noise on hearing.

PMID- 8578418
TI  - Noise, impulse noise, and other physical factors: combined effects on hearing.
AB  - In most of the epidemiologic studies conducted during the last 20 years, impulse
      noise caused increased risk of hearing loss in comparison to continuous noise
      with the same acoustical energy. The interaction between noise exposure
      (broadband at 100 dB(A)) and hand-arm vibration (125 Hz at 2 ms-2 acceleration
      level) has been proven for people having vibration-induced white finger symptoms.
      This interaction is evidenced as a permanent hearing loss. However, why the
      interaction is seen only in people with VWF is not known. The mechanisms may be
      related to individual susceptibility, and hypotheses are given on the role of the
      autonomous nervous system regulating the peripheral vascular reaction. Whole-body
      vibration (2-10 Hz, at 10 ms-2 level) seems to increase the TTS when noise
      (broadband at 90 dB(A)) is present. This effect is more pronounced at higher
      temperatures. The hypothermia protects hearing against the effects of noise in
      animal studies. The interaction between noise and temperature decrease seems
      obvious in animal studies. Exercise has both increased and decreased the TTS
      during noise exposure. The effects have been successfully explained as the
      depression of the stapedius reflex. Thus, less protection against noise is
      provided for the inner ear in exercise conditions. The increase of the blood
      temperature also has been suggested to increase noise-induced TTS during
      exercise. Electromagnetic fields have been found to cause acoustical interactions
      in the inner ear. Animal studies and human studies have given contradictory
      results on the effects of magnetic coil devices on hearing. The MR imaging
      devices produce noise levels of 82-93 dB, which is not sufficient to produce the
      risk of permanent hearing loss when short exposure durations are taken into
      consideration. More systematic research is needed with accurately defined
      electromagnetic characteristics to reveal the potential interactions. The
      interactions seem to exist, but relatively high levels and durations of exposure
      are needed to produce an observable effect on hearing. More investigations are
      still needed on the permanent hearing loss in humans caused by simultaneous long
      term exposures to interacting environmental factors.

PMID- 8578419
TI  - Endogenous factors related to susceptibility to damage from noise.
AB  - There are few endogenous factors related to susceptibility to damage from noise
      other than those that affect the transmission of sound to the cochlea--i.e.,
      characteristics of the outer and middle ears--and a few substances that affect
      the oxygen reaching the cochlea, including oxygen intake itself. Susceptibility
      has not been shown to be dependent on gender, skin color, any known diseases,
      mental attitude toward the noise, exposure history, preexposure hearing loss, nor
      surprisingly, in view of the importance of carbon monoxide--history of smoking.

PMID- 8578420
TI  - Effects of noise and age on the auditory system.

PMID- 8578421
TI  - Presbycusis and occupational hearing loss.

PMID- 8578422
TI  - Combined effects of noise and chemicals.

PMID- 8578423
TI  - Effects of industrial solvents on hearing.

PMID- 8578424
TI  - Epidemiologic considerations in the evaluation of occupational hearing loss.

PMID- 8578425
TI  - Hearing conservation programs for nonserved occupations and populations.

PMID- 8578426
TI  - Economic compensation for hearing loss.

PMID- 8578427
TI  - Historical assessment and future directions in the prevention of occupational
      hearing loss.

PMID- 8578428
TI  - Social work leadership in healthcare: directors perspective.

PMID- 8578429
TI  - Preliminary thoughts on sustaining central social work departments.

PMID- 8578430
TI  - Reflections on effective leadership: strains and successes, strategies and
      styles.

PMID- 8578431
TI  - Crisis or opportunity: a healthcare social work director's response to change.

PMID- 8578432
TI  - The effective health care social work director.

PMID- 8578433
TI  - The effective healthcare social work director: managing the Social Work
      Department at Beth Israel Hospital.

PMID- 8578434
TI  - The evolution of social work in a community hospital.
AB  - Since 1905 social work has had the privilege of working with great medical
      leaders who have respected and assisted our profession. As predicted in 1984 by
      Abraham Lurie, The social work department of the future will be more
      decentralized ... develop stronger links administratively ... knowledge of
      changing social problems ... legislation, research, computerization, data
      gathering and retrieval. The Columbus Regional Hospital Social Work department is
      still early in its development, yet the above predictors have occurred which
      strengthened social work role and professional practice. By 1992 the following
      areas served as a strong foundation for the department's continued growth:
      Resource acquisition Hospital Integration Physician Support We must continue to
      advocate for improved care along with providing an environment of compassion for
      the patients and their families who seek services. Through continued
      participation on hospital committees such as ethics, and utilization review, we
      can demonstrate our practice and influence the environment. By creatively
      accessing resources we can influence and shape opportunities for colleagues. As a
      social work manager I thank those who have come before me who laid framework,
      fought battles and defined territory. We need to continue to support one another
      through collaborative processes and shared experiential learnings.

PMID- 8578435
TI  - Effective leadership: the healthcare social work director.

PMID- 8578436
TI  - From ion currents to genomic analysis: recent advances in GABAA receptor
      research.
AB  - The gamma-aminobutyric acid type A (GABAA) receptor represents an elementary
      switching mechanism integral to the functioning of the central nervous system and
      a locus for the action of many mood- and emotion-altering agents such as
      benzodiazepines, barbiturates, steroids, and alcohol. Anxiety, sleep disorders,
      and convulsive disorders have been effectively treated with therapeutic agents
      that enhance the action of GABA at the GABAA receptor or increase the
      concentration of GABA in nervous tissue. The GABAA receptor is a multimeric
      membrane-spanning ligand-gated ion channel that admits chloride upon binding of
      the neurotransmitter GABA and is modulated by many endogenous and therapeutically
      important agents. Since GABA is the major inhibitory neurotransmitter in the CNS,
      modulation of its response has profound implications for brain functioning. The
      GABAA receptor is virtually the only site of action for the centrally acting
      benzodiazepines, the most widely prescribed of the anti-anxiety medications.
      Increasing evidence points to an important role for GABA in epilepsy and various
      neuropsychiatric disorders. Recent advances in molecular biology and
      complementary information derived from pharmacology, biochemistry,
      electrophysiology, anatomy and cell biology, and behavior have led to a
      phenomenal growth in our understanding of the structure, function, regulation,
      and evolution of the GABAA receptor. Benzodiazepines, barbiturates, steroids,
      polyvalent cations, and ethanol act as positive or negative modulators of
      receptor function. The description of a receptor gene superfamily comprising the
      subunits of the GABAA, nicotinic acetylcholine, and glycine receptors has led to
      a new way of thinking about gene expression and receptor assembly in the nervous
      system. Seventeen genetically distinct subunit subtypes (alpha 1-alpha 6, beta 1
      beta 4, gamma 1-gamma 4, delta, p1-p2) and alternatively spliced variants
      contribute to the molecular architecture of the GABAA receptor. Mysteriously,
      certain preferred combinations of subunits, most notably the alpha 1 beta 2 gamma
      2 arrangement, are widely codistributed, while the expression of other subunits,
      such as beta 1 or alpha 6, is severely restricted to specific neurons in the
      hippocampal formation or cerebellar cortex. Nervous tissue has the capacity to
      exert control over receptor number, allosteric uncoupling, subunit mRNA levels,
      and posttranslational modifications through cellular signal transduction
      mechanisms under active investigation. The genomic organization of the GABAA
      receptor genes suggests that the present abundance of subtypes arose during
      evolution through the duplication and translocations of a primordial alpha-beta
      gamma gene cluster. This review describes these varied aspects of GABAA receptor
      research with special emphasis on contemporary cellular and molecular
      discoveries.

PMID- 8578437
TI  - Role of cyclic AMP in dopamine modulation of potassium channels on rat striatal
      neurons: regulation of a subconductance state.

PMID- 8578438
TI  - Cholecystokinin mobilizes intracellular Ca2+ in hybrid N18TG2 X mesencephalon
      (MES-23.5) cells.

PMID- 8578439
TI  - Biochemical and molecular aspects of the coagulation cascade.

PMID- 8578440
TI  - Thrombolytic therapy: overview of results in major vascular occlusions.
AB  - Thrombolytic therapy provides clinical benefit in patients with vascular
      occlusions, depending upon the organ or limb that is threatened. The impact of
      therapeutic intervention varies from the quiet alteration of the course of deep
      vein thrombosis, for which non-life threatening post-phlebitic syndrome can be
      largely avoided, to the sometimes striking reversal of pulmonary hypertension and
      possible life-saving benefit in massive pulmonary embolism, the immediate
      alteration of clinical course in acute peripheral arterial occlusion by reducing
      the need for surgical intervention, cardiopulmonary complication and one year
      mortality, and finally to the dramatic and life-saving potential when applied in
      patients with acute myocardial infarction. Since the risk of serious hemorrhage,
      especially intracranial hemorrhage, is a constant, regardless of the underlying
      thrombotic problem, thrombolytic therapy will necessarily be applied variably
      according to the different potential therapeutic benefits. The balance of
      potential benefit versus the risk of intracranial hemorrhage in the situation of
      cerebrovascular thrombosis and stroke remains to be clarified by ongoing studies.
      As to the evidence for superiority of any single thrombolytic agent or regimen,
      direct comparative studies are still needed for patients with venous thrombosis
      and arterial occlusion. Available direct comparisons of two or three agents
      (streptokinase, urokinase, alteplase and anistreplase) in studies of pulmonary
      embolism and myocardial infarction show a consistent pattern that documents
      positive clinical benefit for all of the agents, with striking similarity in
      quantitative aspects despite marked differences in biochemical properties of the
      agents.

PMID- 8578441
TI  - Thrombolytic therapy: future issues.
AB  - A considerable amount of work has been devoted to thrombolytic therapy (about
      3000 references from 1991 to 1995 in a Medline search). The most important and
      well established indication of thrombolytic treatment is acute myocardial
      infarction (MI). Megatrials have evidenced a significant 30 to 40% reduction in
      hospital mortality in the treated patients. However, lack of sufficient
      thrombolysis in approximately 25% of patients, reocclusion in 6 to 16% of
      patients and intracranial hemorrhage in about 0.5% of patients are the main
      concerns regarding thrombolysis. Three approaches should improve the results of
      thrombolytic therapy in acute MI: earlier medical treatment, use of more
      efficacious thrombolytic agents in combination with more active antithrombotic
      agents and reduction of severe bleeding with safer combination of drugs. An
      improved of laboratory monitoring may also reduce the incidence of severe
      hemorrhagic events. In acute pulmonary embolism (PE), a change of indication for
      treatment based on echocardiography and high probability ventilation-perfusion
      lung scan results (without requiring pulmonary angiography) could broaden the use
      of thrombolysis. However, thus far, there has not been a demonstration of a
      reduction in mortality in large controlled studies. Thrombolysis in acute
      ischemic stroke is an attractive treatment but thrombolytic treatment is still at
      an experimental stage. However, the successful use of rt-PA in acute MI has
      renewed the interest in thrombolysis for focal cerebro-vascular ischaemia. Large
      controlled studies with SK, rt-PA or UK locally or intravenously administered
      have been recently undertaken to evaluate the benefit/risk ratio of treatment
      which seems surprisingly variable in different subgroups of patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8578442
TI  - Platelet activation: signal transduction via membrane receptors.
AB  - The first stage in signal transduction in platelets is interaction between the
      agonist (or adhesive protein) and its receptor. Changes in conformation or
      clustering induced by binding activate signalling on the cytoplasmic side of the
      platelet membrane. Platelets contain several families of receptors such as the
      leucine rich repeat group, GPIb-V-IX, involved in adhesion to von Willebrand
      factor and modulation of the thrombin response. Platelet integrins include GPIIb
      IIIa (alpha IIb beta 3), the receptor for fibrinogen and the major mediator of
      aggregation, which is also a critical signal transducer both inside-out and
      outside-in to modulate primary signals. Molecules implicated as collagen
      receptors include the integrin alpha 2 beta 1, CD36 and GPVI and involve a novel
      signalling pathway. Many seven transmembrane receptors have been identified;
      current interest is in the proteolytic and purinergic families.

PMID- 8578443
TI  - Flow-related platelet deposition on subendothelium.
AB  - The deposition of platelets on subendothelium is controlled both by flow factors
      that determine their transport to the surface through convective diffusion, and
      by the kinetics of their interactions with the surface. Red cells influence
      platelet transport by several mechanisms, and may also influence platelet
      reactivity. Platelets initially contact the surface through the binding of
      membrane GPIb to von Willebrand factor (vWf) that is present in the
      subendothelium or deposited there from plasma. Platelet spreading on the surface
      is promoted by the binding of the arg1744 gly1745 asp1746 (RGD) region of vWf (at
      high shear rates) to platelet GPIIb-IIIa. At high (arterial) shear rates, vWf
      binding to GPIIb-IIIa also promotes thrombus formation. At these shear rates,
      thrombin that is generated at the subendothelial surface is not involved in
      platelet adhesion or thrombus formation that occurs early in thrombogenesis, but
      is a major mediator of subsequent thrombus growth and/or stabilization.

PMID- 8578444
TI  - Endothelial cell function, including tissue factor expression, under flow
      conditions.
AB  - Vascular endothelium remains a dynamic interface between blood and the vessel
      wall. New developments make clear that many antithrombotic and prothrombotic
      responses of the endothelium depend on flow conditions in an adaptive manner:
      duration of a certain level of shear stress matters as well as level of shear. In
      general, over a time course of several hours, endothelium appears to be more
      actively antithrombotic under moderate shear conditions (e.g., 15 dynes/cm2), and
      more fibrinolytic under high (e.g., 30 dynes/cm2). Pulsatile flow and cyclic wall
      stress further modify these responses. Special consideration, moreover, must be
      given to branch points and regions of irregular geometry (i.e., stenoses,
      aneurysms) in the circulation. In such locations, predilection sites for
      thrombosis, lipid uptake, and atherosclerosis, low levels of fluid shear stress
      (e.g., 0.5 dynes/cm2), large gradients in fluid shear stress, and vessel wall
      bending stresses all become important. Preliminary work suggests that endothelial
      cells in such regions can become prothrombotic, leading to localized platelet
      adhesion/aggregation and fibrin formation on subendothelium and perhaps deeper
      structures following vessel injury.

PMID- 8578445
TI  - Thrombin specificity.
AB  - A model of thrombin interaction with distinct substrates or ligands has been
      derived from the crystallographic studies of thrombin-inhibitors complexes, and
      buttressed by functional studies with mutant thrombins, thrombin proteolytic
      derivatives or antibodies against thrombin. The unique specificity of thrombin
      for its substrates and ligands may be ascribed to multiple interactions with both
      the active site cleft and exosite(s) distinct from the active site. Two prominent
      insertion loops around Trp 50 and Trp 148 project over the active site cleft and
      play an important role in the substrates selection. Several substrates
      (fibrinogen, thrombin receptor, heparin cofactor II) or ligands (thrombomodulin,
      glycoprotein Ib) interact with a large exosite located on the surface of the loop
      segment 65-76, mainly constituted of basic amino acids, designated anion binding
      exosite 1. Interaction with these various macromolecules appears to involve a
      limited number of residues within the large exosite 1. It is conceivable that
      exosite 1 contains distinct subsites, although most of them may overlap. A second
      basic exosite (anion binding exosite 2) is located close to the carboxy-terminal
      B chain helix. Exosite 2 interacts with heparin, the chondroitin sulfate moiety
      of thrombomodulin and prothrombin activation fragment 2. Interaction of ligands
      with either exosite 1 or exosite 2 leads to conformational changes of the
      thrombin molecule, that may be important determinants of thrombin specificity.
      Whether exosite 2 cooperates with exosite 1 for thrombin interaction with
      fibrin(ogen) or the thrombin receptor remains to be determined.

PMID- 8578446
TI  - Thrombin generation in plasma: its assessment via the endogenous thrombin
      potential.
AB  - Thrombin generation is a pivotal function of plasma in haemostasis and
      thrombosis. Its mechanism is essentially the classical cascade, the velocity of
      which is governed by the availability of factors Va and VIIIa and that is
      confined to the surface of the procoagulant membranes which appear at the site of
      injury. There is no routine test that quantitatively renders the thrombin forming
      capacity of a plasma sample. Clotting times (PT-prothrombin time, APTT-activated
      partial tromboplastin time) do not reflect the over all thrombin generation and
      are insensitive to hypercoagulative states. The endogenous thrombin potential
      (ETP), i.e. the area under the thrombin generation curve, better represents this
      function. We developed a method to assess the ETP in the routine laboratory. The
      first results suggest that it is a sensitive indicator for every form of
      anticoagulation. It is increased in hypercoagulable states thus far studied, both
      congenital and acquired and can be designed to indicate deficiencies in protein C
      and S and APC (activated protein C) resistance.

PMID- 8578447
TI  - New molecular insights into the genetics of thrombophilia. Resistance to
      activated protein C caused by Arg506 to Gln mutation in factor V as a pathogenic
      risk factor for venous thrombosis.
AB  - Genetic risk factors are important in the pathogenesis of venous thrombosis, as
      demonstrated by the familial clustering of the disease. However, well defined
      genetic defects were until recently found in less than 10% of the thrombosis
      patients. In 1993, inherited resistance to activated protein C (APC) was reported
      as a novel pathogenetic risk factor for thrombosis. It is found in 20-60% of
      patients with venous thrombosis. APC-resistance is in more than 90% of the cases
      caused by a single point mutation in the gene for factor V (G to A transition at
      nucleotide position 1691), which predicts replacement of Arg(R)506 in the APC
      cleavage site with a Gln(Q). After activation, mutated factor V, FV:Q506, is less
      efficiently degraded by APC than normal factor V, which results in increased
      thrombin generation and a hypercoagulable state. The FV:Q506 mutation is highly
      prevalent in the general population (5-10%). Heterozygosity for FV:Q506 is
      associated with a 5-10-fold increased risk of thrombosis, whereas homozygous
      cases have 50-100-fold increased risk of thrombosis.

PMID- 8578449
TI  - Structure-function relationship of the A1 domain of von Willebrand factor.
AB  - von Willebrand factor (vWF) is a multimeric glycoprotein composed of multiple
      homologous domains. The A1 domain contains a remarkably large disulfide loop of
      185 amino acids (Cys 509-695) which plays a key role in promoting platelet
      adhesion to the subendothelium. Following the initial binding of the A1 domain to
      the subendothelium, a conformational change occurs which allows its binding to
      platelet GPIb. In an attempt to further understand the structure-function
      relationship of the A1 domain, we analyzed 1) the functional properties of
      recombinant vWF mutated on either Cys 509 or 695 and 2) the reactivity of a
      monoclonal antibody (MoAb B724) with vWF conformations interacting with GPIb. Our
      data underline the crucial role of the 509-695 disulfide bond in the binding of
      vWF to GPIb and discriminate the specificity of each Cys in this binding. They
      also indicate that two different conformations of the A1 loop, with high or low
      affinity for MoAb B724, allow the exposure of its GPIb-binding site. Since the
      low affinity conformation is observed in type 2B vWF, MoAb B724 appears as a
      useful tool to probe this type of von Willebrand disease (vWD).

PMID- 8578448
TI  - Function and regulation of the beta 3 integrins in hemostasis and vascular
      biology.
AB  - The beta 3 integrins, alpha IIb beta 3 and alpha V beta 3, are prominently
      expressed on the surfaces of platelets and endothelial cells, respectively. This
      vascular localization places them in a strategic position to perform adhesive
      functions necessary for hemostasis, wound healing and angiogenesis. In addition,
      these integrins are now known to serve a signaling function, whereby
      environmental cues on either side of the plasma membrane can be transmitted
      across the membrane to the other side. Indeed, preliminary studies indicate that
      these dual function receptors are wired to other signaling pathways within
      platelets and endothelial cells, thus helping to explain how integrin-mediated
      cell anchorage can affect cytoskeletal organization and cell motility as well as
      endothelial cell growth, differentiation and apoptosis.

PMID- 8578450
TI  - Molecular mechanism and classification of von Willebrand disease.
AB  - The characterization of mutations in von Willebrand disease provides useful
      insight into the synthesis, structure, and function of von Willebrand factor.
      This growing body of information has prompted a reclassification of vWD types
      that is intended to reflect distinct pathophysiologic mechanisms. Despite this
      apparent progress, many aspects of vWF biology and pathophysiology remain poorly
      understood. These include the mechanism by which binding of vWF to platelets is
      induced at sites of vascular injury, and the factors that influence the
      likelihood of bleeding symptoms in patients with vWD type 1.

PMID- 8578451
TI  - Molecular basis of fibrinolysis, as relevant for thrombolytic therapy.
AB  - The fibrinolytic system comprises an inactive proenzyme, plasminogen, that is
      converted by plasminogen activators to the active enzyme, plasmin, that degrades
      fibrin. Two physiological plasminogen activators have been identified: tissue
      type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u
      PA). Plasminogen activation for clot lysis is regulated by specific molecular
      interactions between tissue-type plasminogen activator (t-PA), plasminogen and
      fibrin, whereby the lysine-binding sites of the plasminogen molecule play a
      crucial role by mediating its binding to fibrin, and by controlling the
      inhibition rate of plasmin by alpha 2-antiplasmin. The recognition that
      thrombosis within the infarct related coronary artery plays a major role in the
      pathogenesis of acute myocardial infarction and the observation that early
      administration of thrombolytic agents results in recanalization of occluded
      coronary arteries, have provided the basis for the development of thrombolytic
      therapy in acute myocardial infarction. The elucidation of the biochemical
      mechanism of fibrin-specific plasminogen activation has fueled the hope that
      specific and efficacious thrombolytic agents might become available. Comparative
      studies between the non-fibrin-selective streptokinase and fibrin-selective
      recombinant t-PA (rt-PA) have shown a difference in efficacy for early coronary
      artery recanalization, whereas the GUSTO trial has established that clinical
      benefit in patients with acute myocardial infarction is indeed correlated with
      the rapidity and frequency of sustained recanalization and that effective
      thrombolysis requires adequate anticoagulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8578452
TI  - The enigma PAI-2. Gene expression, evolutionary and functional aspects.
AB  - The type-2 plasminogen activator inhibitor (PAI-2) belongs to the ovalbumin
      subfamily of serpins. It exhibits close to 50% homology with several recently
      cloned protease inhibitors such as the leukocyte elastase inhibitor, the
      placental thrombin inhibitor and the squamous cell carcinoma antigen. PAI-2
      exists in an intracellular, nonglycosylated form of 47 kDa and a secreted,
      glycosylated form of about 60 kDa. The PAI-2 gene does not have a signal peptide
      which might explain why the major portion of PAI-2 remains intracellularly.
      Several response elements have been identified in the promoter region which are
      necessary for constitutive and phorbol ester and retinoic acid induced expression
      of the gene. These include two AP-1 sites, and response elements for cAMP,
      glucocorticoids and retinoic acid. The physiological function of PAI-2 has not
      been clearly elucidated. It may have cytoprotective functions and appears to play
      a role in programmed cell death.

PMID- 8578454
TI  - Tissue factor: then and now.
AB  - Much has been learned about tissue factor during the past 25 years and much is
      yet to be learned. On the biochemical level, the association of TF:VIIa with
      factor X is yet to be resolved. The mechanism by which TF is transported from the
      nucleus to the plasma membrane has yet to even be approached. Thus, those of us
      studying this interesting and fundamentally important molecule have much work in
      the future.

PMID- 8578453
TI  - Platelet-vessel wall interaction: from the bedside to molecules.
AB  - This paper is an overview of the progress made in the field of platelet-vessel
      wall interaction during the past three quarters of a century. (I) "Prehistoric"
      era (1918-1948): description of Thrombasthenia by 3 European clinicians
      (Glanzmann, Switzerland, 1918), Hereditary Pseudohemophila (von Willebrand,
      Finland 1926) and Congenital Hereditary Platelet Dystrophy (Bernard and Soulier,
      France 1948). (II) Physiopathological era (1957-1972) based on the understanding
      of these 3 disorders: abnormality of platelet adhesion to the vessel wall in von
      Willebrand (vW) and Bernard Soulier syndrome (BSS), abnormality of platelet
      aggregation in thrombasthenias (GT). Breakthrough was made by I.M. Nilsson et al
      in vWD in Aaland Islands with the recognition of a plasmatic anomaly, later
      confirmed by Cornu et al to be different from factor VIII deficiency. (III) The
      third and crucial development (glycoprotein era) (1974-1981) came from the
      discovery by Nurden & Caen (1974-1975) of GPIIb-IIIa defect in GT and of GPIb-IX
      in BSS. Polyclonal antibodies against GPIIb-IIIa and GPIb-IX inhibit clearly ex
      vivo platelet aggregation and adhesion respectively. On everted rabbit
      subendothelium platelet, adhesion was abnormal in BSS whichever shear stress and
      at high shear stress in vWD. (IV) The molecular biology era (1984-1995) with the
      exquisite recognition of gene or protein anomalies in the above mentioned
      disorders together with the cloning of the 3 genes [for vW factor (vWF) (GPIb-IX,
      GPIIb, and GPIIIa]. (V) We are at the dawn of the more crucial era, the
      antithrombotic therapy acting either on the GPIb-vWF complex or on the GPIIb
      IIIa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8578455
TI  - Tissue factor modulation of factor VIIa activity: use in measuring trace levels
      of factor VIIa in plasma.

PMID- 8578456
TI  - Cost effectiveness of diagnosis of deep vein thrombosis in symptomatic patients.
AB  - BACKGROUND: The most widely used noninvasive test for deep vein thrombosis is
      Doppler ultrasonographic imaging of the lower extremities. The best evaluated of
      the noninvasive approaches are ascending contrast venography, impedance
      plethysmography, Doppler ultrasonography with B-mode imaging. Economic evaluation
      is aimed at helping decision makers to reach their goal of maximizing the health
      of the population served, subject to the available resources. METHODS: The data
      that provided the basis for this cost effectiveness analysis were derived from a
      prospective study of approximately 500 patients referred to a regional
      thromboembolism program with a first episode of clinically suspected deep vein
      thrombosis. The application of cost effectiveness analysis to the diagnosis of
      deep vein thrombosis is readily accomplished using cost minimization. This cost
      effectiveness technique makes it possible to rank the diagnostic approaches from
      "worst" to "best", with the best approach defined as that which accomplishes the
      desired health effect at minimum cost. Effectiveness (health benefit) may be
      defined in this context as the number or proportion of patients with deep vein
      thrombosis correctly identified by objective testing or, the number or proportion
      in whom treatment was correctly withheld. RESULTS: Clinical diagnosis is cost
      ineffective; $1,590,784 Canadian, $2,624,220 US. Outpatient diagnosis using
      noninvasive testing was the most cost effective. Serial Doppler ultrasonography
      is more costly ($618,265 Canadian, $1,326,180 US) than serial impedance
      plethysmography ($527,165 Canadian, $1,052,880 US). Combined Doppler
      ultrasonography and serial impedance plethysmography offers a less costly
      strategy ($551,065 Canadian, $1,124,580 US) than serial ultrasonography alone.
      DISCUSSION: Objective testing is mandatory. Outpatient testing is preferred,
      avoiding unnecessary hospital admissions. Noninvasive testing is the most cost
      effective. The most widely used test, serial Doppler ultrasonography, is less
      cost effective than serial impedance plethysmography. The combined approach of
      initial Doppler ultrasonography followed by serial impedance plethysmography
      combines the advantage of an initial ultrasound image with less costly serial
      impedance plethysmography.

PMID- 8578457
TI  - Treatment of venous thromboembolism.
AB  - This review provides meta-analytic data of studies aiming at improved treatment
      of deep vein thrombosis and pulmonary embolism. The introduction of low molecular
      weight heparin has considerably ameliorated the initial treatment of deep vein
      thrombosis, and should now be regarded as the treatment of choice for most
      patients with deep vein thrombosis. Oral anticoagulant treatment is presently
      considered safe and effective for the long-term treatment of venous
      thromboembolism, provided that the INR is maintained at 2.0-3.0. However, the
      optimal duration as well as the optimal intensity of anticoagulation have still
      to be determined. Patients with submassive pulmonary embolism should presently be
      treated with adjusted dose unfractionated heparin and coumarins. Studies
      determining the efficacy and safety of low molecular weight heparin in this
      condition deserve priority. Thrombolytic therapy should be restricted to patients
      with massive pulmonary embolism, unless safer methods of thrombolysis have been
      developed. Surgical embolectomy and catheter fragmentation of emboli seem
      alternative options but deserve further investigations.

PMID- 8578458
TI  - Megakaryocytopoiesis: the state of the art.
AB  - Megakaryocyte development and thrombopoiesis remain enigmatic processes, though
      less so than in the recent past. It is still virtually unknown how these cells
      acquire their signature characteristic, i.e. a hyperdiploid complement of DNA
      within a single nucleus. Why megakaryocytes become hyperdiploid at all also
      remains somewhat mysterious. Since the size of a megakaryocyte tends to correlate
      with the DNA content of its nucleus, it is assumed that development of
      hyperdiploidy allows these relatively rare cells to produce the large numbers of
      platelets that are required on a daily basis. Nevertheless, it has not been
      proven that higher ploidy cells produce more platelets than lower ploidy cells.
      The recent report of an in vitro assay for thrombopoiesis may allow this question
      to be addressed. Of greater significance, this past year has seen the cloning,
      and expression of the hormone thrombopoietin (TPO). This event clearly represents
      a major achievement in this area and which will hopefully assist in answering the
      fascinating biologic questions which remain unsolved in this area. It is also
      hoped that availability of recombinant TPO will prove to be of clinical utility
      as well. The following brief review attempts to summarize current perceptions
      about megakaryocyte developmental biology and the cloning of TPO.

PMID- 8578459
TI  - Regulation of gene transcription during the differentiation of megakaryocytes.
AB  - Glycoprotein IIb (GPIIb) is an early and specific marker of the megakaryocytic
      lineage. Thus studies on the transcriptional regulation of this gene may provide
      helpful information on the mechanisms controlling cell specificity and
      differentiation of this lineage. In previous experiments, the promoter of GPIIb
      gene was isolated and we have shown that a fragment extending 643 bp upstream the
      transcription start site was able to control the cell specificity of a reporter
      gene in transfection experiments of different permanent cell lines. Most of the
      transcriptional activity is contained in an enhancer containing binding sites for
      members of the GATA and ets transcription factors families. The transcription
      factor GATA1 is not only a major regulator of the transcription of erythroid
      genes, but it also regulates the expression of GPIIb and other megakaryocytic
      genes. We suggest that the lineage specificity and the temporal activation of
      GPIIb gene during hematopoiesis rely on the activity of a repressor that has been
      identified on the promoter. To test this hypothesis, we have developed a cell
      model allowing the study of the megakaryocytes differentiation from very immature
      progenitors to fully differentiated cells. This model is based on the
      differentiation of mouse embryonic stem cells. We have obtained megakaryocytes
      together with erythrocytic and granulo-macrophagic cells. The transfection in
      these ES cells of GPIIb promoter constructs mutated or not on different regions,
      including the repressor element will provide important information on the
      mechanisms controlling gene activation or repression during megakaryocyte
      differentiation.

PMID- 8578460
TI  - Thrombosis and inflammation as multicellular processes: significance of cell-cell
      interactions.
AB  - Platelet activation as a result of vascular injury provokes endothelial cells to
      respond in a manner which limits or reverses the occlusive consequences of
      platelet accumulation. If the agonistic forces are strong, platelet accumulation
      is irreversible. In vitro data from our laboratory have repeatedly demonstrated
      that platelets become unresponsive to all agonists when in proximity to
      endothelial cells. This unresponsiveness is due to at least three separate
      endothelial "thromboregulatory" systems: eicosanoids, endothelium-derived
      relaxing factor (EDRF/NO), and most importantly an endothelial cell ecto
      nucleotidase which metabolizes released platelet adenosine diphosphate (ADP) with
      consequent restoration of platelets to the resting state. This nucleotidase is
      operative in the complete absence of EDRF/NO and eicosanoids, indicating that the
      latter two are dispensable thromboregulators. We have solubilized the human
      endothelial cell ectoADPase, as well as that from placental tissue. Candidate
      proteins from a purified ADPase fraction are now being studied in further detail.
      An understanding of the molecular biology of the ADPase gene may lead to
      development of therapeutic agents such as soluble forms of the enzyme as well as
      approaches toward up-regulation of ectoADPase activity. This could result in
      "early thromboregulation", i.e. prevention and/or reversal of platelet
      accumulation at sites of vascular damage via immediate metabolic removal of the
      prime platelet agonist-ADP.

PMID- 8578461
TI  - Platelet activation by polymorphonuclear leukocytes: role of cathepsin G and P
      selectin.

PMID- 8578462
TI  - The molecular basis of platelet and endothelial cell interaction with neutrophils
      and monocytes: role of P-selectin and the P-selectin ligand, PSGL-1.

PMID- 8578463
TI  - The serological investigation of patients with autoimmune thrombocytopenia.
AB  - Techniques for measuring the plasma factor responsible for idiopathic
      thrombocytopenic purpura (ITP) have been sought for some 40 years, but unlike red
      cell serological techniques, platelet antibody testing has proved difficult and,
      at times, generated controversial results. The difficulty in measuring platelet
      antibodies probably reflects the intrinsic nature of the platelet membrane--to
      act as a sponge and nonspecifically bind plasma proteins. There have now been
      three different general types of techniques used to measure platelet
      autoantibodies: phase I assays measuring a platelet-dependent endpoint after
      incubating test serum and control platelets. These assays lack sufficient
      sensitivity and specificity to be useful. Except for special instances (the
      diagnosis of heparin-induced thrombocytopenia), they are no longer used. Phase II
      assays measure IgG on the surface of platelet or within the platelets following
      lysis. The immunoglobulin detected is termed platelet associated IgG. PAIgG
      assays are falling out of favour because they lack the sensitivity and
      specificity to be useful diagnostic tools. Most recently, the ability to isolate
      individual platelet glycoproteins and measure the binding of IgG to these
      glycoproteins has dramatically increased our understanding of ITP. These Phase
      III assays may prove useful diagnostic tools for the investigation and
      classification of immune thrombocytopenic disorders.

PMID- 8578464
TI  - Human platelet alloantigens: recent findings, new perspectives.

PMID- 8578465
TI  - Thrombotic thrombocytopenic purpura.
AB  - Recent studies indicate that CRTTP patients have excessive shear stress-induced
      platelet aggregation that is associated with the presence of ULvWF multimers in
      their plasma and increased vWF-binding to their platelets by flow cytometry. In
      these CRTTP patients, relapses, excessive shear-aggregation and the presence in
      their plasma of ULvWF forms are all reversed by the infusion of normal FFP or
      substances devoid of the largest vWF multimers found in plasma (cryoprecipitate
      poor plasma or cryosupernatant; solvent/detergent-treated plasma) without the
      need for concurrent plasmapheresis. This constellation of observations, along
      with reports of increased vWF in TTP platelet thrombi, increases the probability
      that ULvWF multimers derived from injured or abnormal endothelial cells induce
      aggregation during TTP episodes in high-shear regions of the microcirculation.

PMID- 8578466
TI  - Platelet transfusion.

PMID- 8578467
TI  - The fibrinolytic system: from Petri dishes to genetic engineering.

PMID- 8578468
TI  - Conformational changes in adhesive proteins modulate their adhesive function.
AB  - A large family of glycoproteins mediates cell adhesion by binding to cellular
      receptors. As a group, these adhesive proteins are large in size, multi-domainal
      in composition, and are capable of self-association. A general property of the
      adhesive proteins is their susceptibility to structural modulation, and
      conformational change provides a mechanism for regulation of their adhesive
      functions. To illustrate this concept, conformational alterations of
      thrombospondin, fibrinogen and fibronectin are shown to modulate their adhesive
      potential. Thus, conformational status of the adhesive proteins contributes to
      the regulation of cell adhesion.

PMID- 8578469
TI  - The versatility of adhesion receptor ligands in haemostasis: morpho-regulatory
      functions of vitronectin.

PMID- 8578470
TI  - State and prospects of gene therapy for the hemophilias.

PMID- 8578471
TI  - Biosynthesis of factor IX: implications for gene therapy.

PMID- 8578472
TI  - Cancer and thrombosis: from Phlegmasia alba dolens to transgenic mice.
AB  - Thrombosis is the most frequent complication and the second cause of death in
      patients with overt malignant diseases. Increasing evidence suggests that
      thrombotic episodes may also precede the diagnosis of cancer by months or years
      thus representing a potential marker for occult malignancy. Recently, emphasis
      has been given to the potential risk of cancer therapy (both surgery and
      chemotherapy) in enhancing the risk for thromboembolic disease. Post-operative
      deep-vein thrombosis is indeed more frequent in patients operated for malignant
      diseases than for other disorders. On the other hand, both chemotherapy and
      hormone therapy are associated with an increased thrombotic risk, which can be
      prevented by low-dose oral anticoagulation. Possible contributory causes for
      thromboembolic disease in cancer include the capacity of tumor cells and their
      products to interact with platelets, clotting and fibrinolytic systems, as well
      as their interactions with endothelial cells and tumor-associated macrophages. In
      particular, procoagulant activities of tumor cells have been extensively studied;
      one of these, cancer procoagulant, could represent a novel marker of malignancy
      in both solid tumors and acute promyelocytic leukemia (APL). In solid tumors, CP,
      a vitamin K dependent enzyme could represent the selective target of the
      antimetastatic effects of warfarin treatment. In APL, CP may contribute to
      trigger the well known intravascular coagulation syndrome accompanying the early
      manifestations of the disease and is depressed by all-trans-retinoic acid, an
      agent capable to determine complete remission with a rapid amelioration of the
      bleeding syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8578473
TI  - Role of platelets, thrombin, integrin IIb-IIIa, fibronectin and von Willebrand
      factor on tumor adhesion in vitro and metastasis in vivo.
AB  - The role of platelets and thrombin was examined in tumor cell adhesion in vitro
      and metastasis in vivo. Adhesion of tumor cells to platelets was inhibited by
      agents inhibiting platelet integrin IIb-IIIa receptor occupancy (MoAb 10E5 and
      tetrapeptide RGDS) as well as IIb-IIIa ligands (polyclonal antibodies against
      fibronectin and von Willebrand factor (vWF)). In vivo murine experimental
      pulmonary metastasis (tail vein injection) could be inhibited by antibody-induced
      induction of thrombocytopenia and reconstituted by simultaneous injection of
      human platelets. Preincubation of human platelets with MoAb 10E5 (vs IIb-IIIa)
      inhibited reconstitution of metastasis. Thrombin activates tumor cell adhesion to
      platelets by activating platelets as well as tumor cells. Thrombin-activated
      tumor cells also enhance their adhesion to endothelial cells as well as adhesive
      ligands fibronectin and vWF. Experimental pulmonary metastasis is enhanced 4-400
      fold by preinfusion of thrombin into mice or 10-160 fold by prior treatment of
      tumor cells with thrombin. The in vitro and in vivo effects of thrombin were
      mimicked by thrombin receptor activation peptides SFLLRNPNDKYEPF and SFLLRN. Nine
      of nine tumor cell lines have the seven transmembrane spanning thrombin receptor
      detected by the polymerase chain reaction. Thus, both platelets and thrombin
      contribute to experimental tumor metastasis by fostering and enhancing IIb-IIIa
      integrin platelet interaction with tumor cells. Since many tumor cells generate
      thrombin, it is proposed that tumor cells may autoactivate a metastatic
      phenotype.

PMID- 8578474
TI  - Platelets and plasminogen activation.
AB  - Platelets serve as a site for assembly of the proteins of the plasminogen
      activator system. Once bound to the platelet surface, tissue-type plasminogen
      activator manifests enhanced catalytic activity. Plasmin, once formed, also binds
      to the platelets surface and, at low concentrations, renders the platelet
      dysfunctional by cleaving glycoprotein IIIa selectively in the presence of bound
      fibrinogen. At higher concentrations (approximately 1 caseinolytic unit/ml),
      plasmin activates the platelet directly. Activated platelets also bind
      plasminogen and tissue-type plasminogen activator, and manifest enhanced
      catalytic efficiency of plasminogen activation. These observations suggest that
      plasminogen activation by tissue-type plasminogen activator is an autocatalytic
      process on the platelet surface, and that unique reciprocating mechanisms govern
      the interaction between platelets and the components of the plasminogen activator
      system.

PMID- 8578475
TI  - Cellular receptors in the regulation of plasmin generation.
AB  - Cell surface receptors may play a significant role in the regulation of plasmin
      generation. Although structurally diverse, these receptors can be classified on a
      functional basis into two groups. Activation receptors for plasminogen and
      plasminogen activators serve to localize, and in some cases, potentiate
      plasminogen activation, and are expressed on endothelial cells, blood cells,
      neuronal cells, and tumor cells. Clearance receptors, on the other hand, serve to
      eliminate plasmin and plasminogen activators from blood or focal micro
      environments. They are found primarily on parenchymal hepatocytes and tissue
      macrophages. It is likely that integrated actions of both classes of receptors
      are essential to the homeostatic control of plasmin activity. Knowledge of how
      these receptors themselves are regulated may provide an important key to
      understanding a host of biologic processes.

PMID- 8578477
TI  - Molecular organization and functional regulation of cell to cell junctions in the
      endothelium.
AB  - Intercellular junctions are important structural determinants of endothelial
      permeability. These organelles are formed by a complex network of transmembrane
      proteins linked to a well developed plasmalemmal undercoat. One of the typical
      characteristics of endothelial junctions is their dynamic organization.
      Endothelial cells are able to rapidly change the architecture of the junctions to
      allow the passage of plasma constituents and circulating cells. This effect, in
      most of the cases, is quickly reversible and the endothelium is able to
      disorganize/reorganize the intercellular junctions within minutes. The mechanisms
      that regulate the opening and the closure of endothelial junctions are still
      obscure. It is conceivable that inflammatory agents increase permeability by
      binding to specific receptors generating intracellular signals which in turn
      cause cytoskeletal reorganization and opening of interendothelial gaps.
      Endothelial junctions also control leukocyte extravasation. Once leukocytes have
      adhered to the endothelium, a coordinated opening of interendothelial clefts
      occurs. The mechanism by which this takes place is unknown, but it might present
      characteristics similar to that triggered by soluble mediators.

PMID- 8578476
TI  - New antiplatelet agents: platelet GPIIb/IIIa antagonists.
AB  - The GPIIb/IIIa (alpha IIb beta 3) receptor plays a crucial role in platelet
      aggregation and platelet thrombus formation. Inhibition of GPIIb/IIIa with the
      Fab fragment of the mouse/human chimeric monoclonal antibody 7E3, snake venom
      peptides containing the arginine-glycine-aspartic acid (RGD) sequence, or
      peptides or peptidomimetics based on the RGD sequence results in abolition of
      platelet aggregation and platelet thrombus formation. This results in profound
      inhibition of thrombotic occlusions in animal models. The Phase III EPIC study
      demonstrated that c7E3 Fab, given as bolus followed by a 12 h infusion, reduced
      the risk of acute ischemic complications after coronary angioplasty by
      approximately 35% in patients at high risk of suffering such complications.
      Treated patients had an approximately 2-fold increased risk of major bleeding,
      but no increase in cerebral hemorrhage or lethal bleeding. Treatment with c7E3
      Fab may have had a beneficial effect on clinical restenosis at 6 months, but this
      needs to be confirmed. A possible anticoagulant effect of c7E3 Fab was also
      identified in EPIC, and in vitro studies support this possibility. With the
      approval of c7E3 Fab (abciximab; ReoPro) for patients undergoing high-risk
      angioplasty in the US and several European and Scandinavian countries, GPIIb/IIIa
      inhibition joins the armamentarium of antithrombotic agents.

PMID- 8578478
TI  - Inherited factor VII deficiency: genetics and molecular pathology.

PMID- 8578479
TI  - Molecular genetics of coagulation factor VIII gene and hemophilia A.
AB  - This review summarizes the structure of human coagulation factor VIII gene and
      its deduced protein sequence and the molecular etiology of hemophilia A in man.
      The gross DNA rearrangements including the common inversions of factor VIII
      (which account for about 45% of severe hemophilia A patients), and the point
      mutations are discussed. The functional consequences of certain missense
      mutations are illustrated.

PMID- 8578480
TI  - Protean clinical presentation of antiphospholipid-protein antibodies (APA).
AB  - Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which
      have been defined by varying laboratory test systems. Lupus anticoagulants (LA)
      and anticardiolipin antibodies (ACA) are the two most prominent members of this
      family of antibodies. LA are detected utilizing various phospholipid (PL)
      dependent tests of coagulation (e.g., activated partial thromboplastin time
      [APTT], Kaolin Clotting Time [KCT], dilute Russell Viper Venom Time [dRVVT]).
      Originally, LA were thought to be a laboratory nuisance since the vast majority
      of individuals with LA did not bleed. Paradoxically, patients with LA were found
      to have an increased incidence of thromboembolic events and also recurrent
      spontaneous abortions (RSA). Thus, the laboratory detection of LA has become part
      of the work up of patients with thromboembolic disorders and RSA. ACA are
      detected using solid phase assay systems (radioimmunoassay or ELISA). The
      presence of ACA has the same clinical implications as that of LA. Although
      originally it was suggested ACA and LA were the same antibody, it is now well
      accepted that they, in many instances, are different antibodies. Therefore, it is
      critical for laboratories to evaluate patient samples for both LA and ACA. In
      approximately 60% of circumstances, both antibodies will be found. In the
      remaining cases, there will be discordance between the two test systems. The
      question of whether APA are causative, coincidental, or a consequence of the
      clinical complications of RSA and thrombosis remains controversial. Recent
      evidence based on prospective clinical studies and analysis of markers of in vivo
      coagulation suggests APA are causative.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8578481
TI  - Diagnostic methodologies for circulating anticoagulants.
AB  - Various types of circulating anticoagulant are encountered in coagulation testing
      laboratories. Those associated with bleeding often cause problems in diagnosis.
      The most common type of acquired coagulation inhibitor not associated with
      bleeding is the so-called lupus anticoagulant (LA). Differing from SLE which
      occurs predominantly in women, primary LA occurs both in females and males. LA
      are now frequently sought in patients with recurrent foetal losses and acquired
      thrombotic problems as a causative factor, whereas in the past they were regarded
      as a laboratory nuisance. Due to the complicating effect of inhibitors on
      clotting tests, diagnosis of various coagulation inhibitors remains difficult.
      There may also be significant overlap between different types of inhibitors. With
      the recent interest shown in LA, almost all non-specific inhibitors tend to be
      classed as LA. LA are defined as phospholipid-interfering antibodies. Current
      criteria have recently been confirmed and include screening with phospholipid
      responsive tests, abnormal mixing studies and correction with phospholipids.
      However it is becoming clear that even LA as defined may be heterogeneous. Most
      LA are not directed at negatively-charged phospholipids alone as originally
      suggested, but rather at complexes of either beta-2-glycoprotein 1 or prothrombin
      with such phospholipids. There may also be other lipid-associated antigens
      involved. Although earlier work suggested that all LA functioned through a
      similar mechanism, there is now some preliminary evidence suggesting that various
      subclasses of LA may account for discrepant results sometimes obtained with
      different clotting tests. A variety of improvements to the basic screening tests
      for LA (APTT, KCT, DTTI and DRVVT) have recently been suggested.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8578482
TI  - Polymorphisms of human platelet membrane glycoproteins: structure and clinical
      significance.
AB  - The haemostatic response of platelets of any one individual will be influenced by
      the genetic profile of the total population of receptors expressed on the
      platelet surface. Among the parameters to consider will be (i) the density of
      each receptor, (ii) the rate at which genes are transcribed and receptors
      produced and (iii) the presence or not of structural polymorphisms. Already,
      consideration of the known polymorphisms on GP IIb and GP IIIa raises most
      interesting questions on the structure/function relationship for this receptor.
      For example, there is often no obvious pattern as to which polymorphisms will
      influence platelet function and which will risk giving rise to a diallelic
      alloantigen system. Thus, mutation at Arg214 results in a loss in the ability of
      the complex to support platelet aggregation, whereas a mutation at Arg143 has
      resulted in the production of an immune response (see above). As I have pointed
      out earlier, examples from inherited platelet disorders show that even a single
      mutated allele can influence receptor function. Others have shown that
      polymorphisms of plasma proteins (see 52) or membrane glycoproteins such as E
      selectin of endothelial cells (see 53) can give rise to risk factors for
      thrombosis and/or atherosclerosis. It would be interesting to know whether
      polymorphisms of platelet glycoprotein receptors (and those shared with other
      vascular cells) also represent risk factors in cardiovascular disease.

PMID- 8578483
TI  - Platelet integrins.

PMID- 8578484
TI  - AIDS and hemophilia--current issues.

PMID- 8578485
TI  - Low molecular weight heparins (LMWH) in the treatment of patients with acute
      venous thromboembolism.
AB  - We have analysed randomized trials comparing unfractionated heparin and low
      molecular weight heparin in which symptomatic recurrent venous thromboembolism
      and major bleeding were objectively confirmed. Studies were classified as level 1
      if they were double blind or if there was blinded assessment of outcome measures
      and level 2 if they did not provide assurance of blinded outcome assessment. In
      studies classified as level 1, the relative risk (RR) of recurrent venous
      thromboembolism during the first 15 days and over the entire period of
      anticoagulant therapy was 0.24 (95% confidence intervals [CI] 0.06-0.08, p =
      0.02) and 0.39 (95% CI 0.3-0.4, p = 0.006), respectively, in favour of LMWH
      treatment. The RR for major bleeding was 0.42 (95% CI 0.2-0.9, p = 0.01), in
      favour of LMWH. In studies classified as level 2, no significant differences in
      the rates of recurrent venous thromboembolism and major bleeding were observed.
      Pooling level 1 and level 2 studies, the RR for overall mortality and mortality
      in cancer patients was 0.51 (95% CI 0.2-0.9, p = 0.01) and 0.33 (95% CI 0.1-1.8,
      p = 0.01) respectively, in favour of LMWH.

PMID- 8578486
TI  - Effectiveness and safety of low molecular weight heparins (LMWH) in the
      prevention of venous thromboembolism (VTE).
AB  - Several recently published clinical trials have shown that prophylaxis against
      postoperative venous thromboembolism with LMWHs is justified on the basis of
      proven efficacy, safety, better patient acceptability and saving of nursing time.
      The cost effective analyses also indicate substantial savings can be achieved by
      using LMWHs, particularly in the high-risk patients. It is believed that emphasis
      is now on the clinicians who must protect all high-risk patients.

PMID- 8578487
TI  - Mechanisms involved in platelet vessel wall interaction.
AB  - The molecular mechanisms underlying formation of platelet thrombi constitute one
      of the central problems in vascular biology and medicine. Fibrinogen binding to
      its platelet integrin receptor alpha IIb beta 3 (glycoproteins IIb-IIIa complex)
      plays a pivotal role in formation of platelet thrombi by providing molecular
      bridges spanning platelets and by contributing to its receptor-mediated outside
      in signaling. Conversely, fibrinogen binding to integrin alpha IIb beta 3
      requires inside-out signaling mediated by intraplatelet signal transducers
      activated in response to external signals generated at the site of vascular
      injury. This tightly regulated fibrinogen-integrin alpha IIb beta 3 interaction
      constitutes a fundamental platelet mechanism of response to vascular injuries
      such as accidental and surgical wounds, rupture of atherosclerotic plaques in
      coronary and cerebral atherosclerosis and microvascular endothelial desquamation
      in septic shock. After mapping the fibrinogen site on the gamma chain responsible
      for recognition of platelet integrin alpha IIb beta 3 and the development of
      synthetic peptide inhibitors, we solved the 3D structure of the carboxy-terminal
      segment of the human fibrinogen gamma chain using our new technology of carrier
      protein-driven crystallization. Fundamental knowledge concerning a molecular 3D
      model of fibrinogen-integrin alpha IIb beta 3 interaction, coupled to the
      mechanism of its inside-out and outside-in regulation, will lead to development
      of a new generation of platelet-selective antithrombotic drugs.

PMID- 8578488
TI  - Application of combinatorial libraries and protein engineering to the discovery
      of novel anti-thrombotic drugs.
AB  - Combinatorial libraries and protein engineering represent two new powerful tools
      in drug discovery and development. The application of a combinatorial ssDNA
      library to thrombin led to the discovery of a sequence-specific nucleotide-based
      thrombin inhibitor (thrombin aptamer). The thrombin aptamer has a novel tertiary
      structure revealed by NMR and shows potent rapid anticoagulation with a short
      half-life in vivo. It has been used successfully to replace heparin in a canine
      cardiopulmonary bypass model. Functional mapping of the surface residues of
      thrombin led to the generation of a modified thrombin with markedly diminished
      procoagulant properties while retaining its ability to activate protein C. This
      engineered thrombin functions as a protein C activator and demonstrates potent
      anticoagulation in vivo without prolongation of the bleeding time.

PMID- 8578489
TI  - Clinical trials of primary and secondary prevention of thrombosis and restenosis.
AB  - In the primary prevention of arterial disease, there may be a role for anti
      oxidant vitamins and for oestrogen replacement therapy in postmenopausal women.
      For the secondary prevention of thrombotic complications of atherosclerosis,
      aspirin has proven efficacious in reducing both mortality and morbidity. Patients
      with ischaemic heart disease and moderately elevated serum cholesterol benefit
      from simvastatin administration. Heparin and oral anticoagulants are the mainstay
      in the primary and secondary prevention of venous thrombosis. More potent
      antithrombotic compounds, the direct thrombin inhibitors and the glycoprotein IIb
      IIIa antagonists, are mainly being evaluated in emergency coronary medicine.
      Preliminary results are encouraging but haemorrhagic problems need to be solved.
      The trend toward a decrease in late restenosis following coronary angioplasty
      using a IIb-IIIa antagonizing Fab fragment may prove to be a major therapeutic
      breakthrough.

PMID- 8578490
TI  - Lipoprotein(a), plasmin modulation, and atherogenesis.
AB  - Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein however the mechanisms by
      which Lp(a) promote the atherosclerotic process are not clear. The
      apolipoprotein(a) portion of Lp(a) shares partial homology with plasminogen, a
      finding that has stimulated numerous studies. Lp(a) binds to fibrin and the
      affinity between fibrin surfaces and Lp(a) appears to be related to the state of
      oxidation of the lipoprotein particle. Lp(a) also effects fibrin-dependent
      plasminogen activation. Recent findings suggest that dependent plasminogen
      activation. Recent findings suggest that depending upon the in vitro conditions,
      Lp(a) either promotes or inhibits plasmin formation. Lp(a) also inhibits cell
      surface dependent plasmin generation that is associated with an inhibition of
      transforming growth factor-beta (TGF-beta) production in cell coculture systems.
      Lp(a) stimulates smooth muscle cell migration and proliferation as a secondary
      response to this decrease in TGF-beta concentration. Studies in transgenic mice
      containing the human apolipoprotein(a) gene, document that both plasmin and TGF
      beta formation in the media of the aorta is markedly decreased in the presence of
      apo(a). Thus the atherogenicity of Lp(a) may be mediated, in part, through its
      modulation of plasmin and TGF-beta production in the blood vessel wall.

PMID- 8578491
TI  - Fibrinolytic agents: mechanisms of activity and pharmacology.
AB  - Fibrinolytic (thrombolytic) agents activate the fibrinolytic system by conversion
      of the inactive proenzyme, plasminogen into the active enzyme plasmin, that
      degrades fibrin. Agents available for clinical use are: the physiologic tissue
      type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA)
      -either in a single chain (scu-PA, prourokinase) or a two-chain (tcu-PA,
      urokinase) form, and the bacterial activator plasminogen streptokinase or its
      anisoylated complex with plasminogen (APSAC). Despite their widespread use,
      mainly in patients with acute myocardial infarction, all these agents suffer from
      a number of significant limitations, including resistance to reperfusion, the
      occurrence of acute coronary reocclusion and bleeding complications. Several
      lines of research towards improvement of thrombolytic agents are being explored,
      including the construction of mutants and variants of plasminogen activators,
      chimeric plasminogen activators, or plasminogen activators from animal (e.g.
      vampire bat) or bacterial (e.g. staphylokinase) origin. Pilot studies in patients
      with acute myocardial infarction have been performed with a few selected agents.
      Definition of their relative therapeutic benefit, or lack thereof, will require
      more detailed dose-finding studies, followed by randomized clinical trials
      against presently available thrombolytic agents.

PMID- 8578492
TI  - Tissue factor expression in human leukocytes and tumor cells.
AB  - Tissue factor (TF) exists in a cryptic form [i.e. without procoagulant activity
      (PCA)] in peripheral blood monocytes and quiescent tissue macrophages but is
      expressed constitutively in most human tumor cells. Induction and cell surface
      expression of TF in these cells in vivo is associated with activation of
      intravascular and extravascular coagulation in patients with a variety of
      inflammatory or malignant diseases. The regulation of TF synthesis in cells is
      complex and new information from transfection studies suggests that changes in
      cellular glycosylation pathways impair cell surface expression of functional TF.
      Such dysregulation may also characterize the lineage-unfaithful expression of TF
      in leukemic cells and perhaps explain some of the thrombohemorrhagic
      complications in patients with acute progranulocytic leukemia. The importance of
      carbohydrate modification of TF is reviewed.

PMID- 8578493
TI  - Characterization of biochemical and functional effects of antiplatelet drugs as a
      key to their clinical development.

PMID- 8578494
TI  - Molecular genetics and counselling in haemophilia.
AB  - Genetic analysis of the human factor VIII and IX genes has resulted in accurate
      carrier detection and prenatal diagnosis based on either informative DNA
      polymorphisms or on causative mutations. By combined use of up to 10
      polymorphisms within the factor IX gene, over 90% of families are informative.
      Within the factor VIII gene the multiallelic CA repeats in introns 13 and 22 can
      be analysed by multiplex PCR resulting also in over 80% of families being
      informative. Mutation detection has developed with advancing technology which can
      be used to identify mutations in the factor IX gene in practically all patients
      with haemophilia B and their relatives. Although this is more technically
      demanding for patients with haemophilia A because of the greater complexity of
      the factor VIII gene, the recent description of X-chromosome inversions as a
      cause of severe haemophilia A in almost 50% of patients has led to the ready
      detection of these inversions in such families with associated precise carrier
      detection.

PMID- 8578495
TI  - Antiplatelet therapy with aspirin: from clinical trials to practice.

PMID- 8578496
TI  - Inhibition of intravascular thrombosis and vascular smooth muscle cell
      proliferation by gene therapy.
AB  - Intravascular thrombosis, smooth muscle cell proliferation and matrix production
      lead to arterial luminal narrowing and reduction of blood flow to various organs.
      Alteration of gene expression of the arterial wall cells to inhibit thrombosis
      and smooth muscle activation is emerging as a new and exciting therapeutic
      modality for cardiovascular pathology. We have used genetically modified
      endothelial cells to seed endovascular prostheses and tested cell adhesion to the
      prostheses both in vitro and in vivo. We also used two catheter-based systems to
      deliver genes directly to the arterial wall cells in vivo employing retroviral
      and adenoviral vectors. With efficient vectors for gene transfer and high level
      expression of proteins by the transduced cells, gene therapy will serve as a
      major therapy for post-angioplasty restenosis, unstable angina pectoris and
      vascular grafts stenosis.

PMID- 8578498
TI  - Developmental hemostasis: relevance to thromboembolic complications in pediatric
      patients.

PMID- 8578497
TI  - Molecular mechanisms of fibroblast growth factor-1 traffick, signaling and
      release.

PMID- 8578499
TI  - Fetal neonatal thrombocytopenia.

PMID- 8578500
TI  - Gene targeting and gene transfer studies of the biological role of the
      plasminogen/plasmin system.
AB  - A possible role of the plasminogen/plasmin or fibrinolytic system in several
      biological processes has been implied from correlations between fibrinolytic
      activity and (patho)physiological phenomena. However, such indirect evidence does
      not allow to definitively establish the biological relevance of this system. Two
      recently developed technologies, gene targeting and gene transfer, have allowed
      to more definitively characterize the in vivo role of gene products. The
      consequences of gain or loss of function of fibrinolytic system components on
      reproduction, development, health, survival and on hemostasis, thrombosis,
      neointima formation, tissue remodeling, brain function, malignancy and
      neovascularization is summarized below. In addition, the possible use of
      transgenic mice to study gene regulation or to generate monoclonal antibodies
      against conserved epitopes in the targeted proteins is discussed.

PMID- 8578501
TI  - Effects of factor VIII concentrates on the immune system of patients with
      hemophilia.
AB  - The introduction of high-purity factor VIII (FVIII) concentrates in the treatment
      of patients with hemophilia A has raised the issue that the use of these products
      may change on the immune system of the recipients. There is now clear evidence
      that high-purity concentrates, particularly those produced by immune-affinity
      chromatography or recombinant DNA technology, slow the fall in CD4 cells that
      occurs in HIV seropositive patients. It remains to be demonstrated that this
      biological effect results in clinical benefits and that the occurrence of AIDS is
      slowed or delayed by the use of high-purity concentrates. On the other hand,
      concern has been expressed about the possibility that high-purity products might
      render patients with hemophilia less immunotolerant, facilitating the onset of
      FVIII antibodies. Follow-up studies of previously untreated hemophiliacs infused
      for the first time with recombinant FVIII products have ignited this concern,
      because approximately one fourth of severe hemophiliacs developed inhibitors.
      However, most of the inhibitors were transient, so that ultimately they had
      little influence on the efficacy of replacement therapy. It was subsequently
      realized that inhibitors develop with high frequency even in hemophiliacs treated
      with less pure, plasma-derived products, provided testing is prospective and as
      frequent as for studies of recombinant FVIII. On the whole, these data have
      provided new insights on the natural history of inhibitor development in
      previously untreated hemophiliacs, showing that low-titer, short-lasting
      inhibitors develop more frequently than previously recognized.

PMID- 8578502
TI  - Some aspects on the management of hemophilia.

PMID- 8578503
TI  - Activated protein C resistance: molecular mechanisms.
AB  - Activated protein C (APC) resistance is usually associated with a single DNA
      mutation predicting replacement of Arg506 by Gln in factor V (FV). Studies using
      synthetic peptides suggest that FV residues 493-506 provide factor Xa (FXa) and
      protein S binding sites. Biochemical studies were performed to test the
      hypothesis that the Arg506Gln FV mutation causes APC resistance and to define the
      nature of the resistance of Gln506-FVa to APC. Purified Gln506-FV conveyed APC
      resistance to FV-deficient plasma in APTT and FXa-1-stage assays. Purified Gln506
      FVa, generated either by thrombin or by FXa, was resistant to APC. Nonetheless,
      Gln506-FVa was not completely resistant to APC since it was inactivated by APC
      approximately 10-fold slower than normal Arg506-FVa, probably due to cleavage at
      Arg306. This reduced but significant susceptibility of Gln506-FVa to APC
      inactivation may help explain why APC resistance, especially for heterozygotes,
      is a relatively moderate risk factor for venous thrombosis. Cardiolipin promotes
      APC anticoagulant activity better than FXa coagulant activity, and antibodies
      from some antiphospholipid antibody syndrome patients downregulate APC activity.
      Thus, acquired APC resistance may contribute to pathogenesis of thrombosis in the
      antiphospholipid antibody syndrome.

PMID- 8578504
TI  - Resistance to activated protein C and factor V Leiden as risk factors for venous
      thrombosis.
AB  - The recent discovery of the factor V Leiden mutation as the molecular defect in
      the large majority of APC-resistant individuals, has drastically changed our view
      on familial thrombophilia and it has contributed to a better understanding of the
      interaction of genetic and environmental risk factors. It has offered firm
      support for the view that venous thrombosis is a multifactorial disease and that
      the risk of thrombosis will increase as the number of genetic and/or
      environmental risk factors increases.

PMID- 8578505
TI  - Progress towards gene therapy for the hemophilias.
AB  - A variety of vector systems and approaches for transferring the genes for factors
      VIII and IX are being investigated. This indicates that there is no clearly
      superior technique that has emerged. However, considerable progress is being made
      in factor expression in animal models. In addition, as mechanisms of vector
      biology are elucidated, this facilitates more rational design of vector
      improvements.

PMID- 8578506
TI  - Platelet adhesion to collagen.

PMID- 8578507
TI  - The role of von Willebrand factor and fibrinogen in the initiation of platelet
      adhesion to thrombogenic surfaces.
AB  - Platelets respond rapidly to alterations of endothelial cells by attaching firmly
      to the site of lesion, where exposure of subendothelial components may have
      occurred. The first layer of platelets is in contact with the thrombogenic
      surface (adhesion), whereas subsequent growth of the hemostatic plug depends on
      platelet-to-platelet interactions (aggregation). Both aspects of platelet
      function are influenced by von Willebrand factor and fibrinogen interaction with
      specific platelet membrane receptors. Multiple domains of von Willebrand factor
      and fibrinogen are involved in securing initiation and growth of platelet
      thrombi.

PMID- 8578508
TI  - Antithrombotic benefits and hemorrhagic risks of direct thrombin antagonists.

PMID- 8578509
TI  - Comparative pharmacology of site directed antithrombin agents. Implication in
      drug development.
AB  - Beside the direct inhibition of thrombin and its regulatory functions, many of
      the newer antithrombin agents produce several additional effects, unrelated to
      their anticoagulant actions. Synthetic peptide inhibitors are capable of
      producing fibrinolytic compromise by virtue of their actions on fibrinolytic
      enzymes such as t-PA, plasmin, urokinase and protein Ca. In addition, the low
      molecular weight arginine-containing peptides are also known to produce
      hemodynamic and hemostatic deficits. The designs of the ongoing clinical trials
      are largely empirical because of the non-availability of valid pharmacologic and
      toxicologic data on thrombin inhibitors. In contrast to heparin, none of the
      thrombin inhibitors produce endogenous release of tissue factor pathway inhibitor
      (TFPI) in the experimental and clinical settings. These observations suggest that
      beside the direct inhibition of thrombin, these agents also produce multiple
      additional effects that can significantly contribute to their pharmacologic and
      toxicologic profile.

PMID- 8578510
TI  - Fibrin sealant in the United States: clinical use at the University of Virginia.
AB  - Fibrin sealant use in the United States has been limited because of the lack of a
      commercially available, government approved product. However, the significant
      need and usefulness of this material at the time of surgical operations has
      stimulated alternative sources of production. At the University of Virginia, the
      Blood Bank produces concentrated single donor or autologous fibrinogen for use
      with commercially available bovine thrombin in order to make fibrin sealant. The
      hemostatic and adhesive properties of fibrin sealant have been used since 1985 at
      this Center in a wide variety of operations with over 90% effectiveness. This
      chapter will review the development and role of this material in modern clinical
      surgery at this institution. The advantages, disadvantages, and never
      applications of this substance in various forms will be assessed. The role of
      fibrin sealant is increasing in this country and additional developmental work is
      continuing. The era of a commercially available product in the United States
      appears to be on the horizon.

PMID- 8578511
TI  - Fibrin sealant in surgery of patients with a hemorrhagic diathesis.
AB  - The utilization of fibrin sealants in patients with hemostatic disorders has
      hitherto been very limited. Our experiences from 40 major and 8 minor surgical
      procedures, 10 circumcisions and 118 tooth extractions in 106 patients with
      hemophilia A, B or von Willebrand's disease, almost exclusively of the severe
      form, respectively, demonstrate the benefits regarding reduction of blood loss
      and requirements for systemic replacement therapy. The literature on the use of
      fibrin sealants in this group of patients, which mainly concerns dental
      procedures, is reviewed and compared with our data. The importance of the
      composition of the glue is also discussed in detail.

PMID- 8578512
TI  - Thrombin functions and antithrombotic intervention.

PMID- 8578513
TI  - Issues in the development of thrombin receptor antagonists.
AB  - The identification of the human thrombin receptor has prompted considerable
      interest in the development of receptor antagonists that can inhibit the effects
      of thrombin on cells without affecting fibrin formation. Increasing information
      about the biology of the receptor highlights some of the potential pitfalls in
      the development and application of such agents. However, it also provides
      additional insights into the potential mechanisms by which an antagonist might
      work beyond the original approach of developing competitive inhibitors of the
      tethered ligand domain. Thrombin receptors have proved to be present on a variety
      of cells other than platelets, including other vascular cells and cells within
      the central nervous system. Although most of the recent emphasis in thinking
      about the need for anti-thrombin receptor agents has focused on their use as anti
      platelet agents, it is worth considering that the best clinical uses of such
      drugs may ultimately prove to have little to do with platelets.

PMID- 8578514
TI  - Oral anticoagulant treatment with and without aspirin.
AB  - For preventing thromboembolic events, the concurrent use of oral anticoagulant
      and antiplatelet drugs has been proposed. In prosthetic heart valves the use of
      moderate intensity anticoagulants [International Normalized Ratio (INR) 2-3] plus
      aspirin (100 mg/day) decreases the amount and severity of embolic episodes. The
      possibility that the same regimen could provide benefit in the prevention of
      thrombotic events in other arterial diseases is also indicated by the ATACS trial
      in unstable angina. The ongoing studies in ischemic heart diseases will also give
      the answer to this possibility.

PMID- 8578515
TI  - Clinical coagulation laboratory and oral anticoagulant therapy treatment.
      Instrumentation and methodology.
AB  - To assess the organization and the quality of care of an anticoagulation clinic,
      the structure, the process of laboratory control and the clinical outcome in our
      Center are described. 1068 patients under control in 1994 (M/F 572/496; median
      age 63 range 6-91 ys., 74% in long-term prophylaxis) were evaluated. The clinic
      was run twice weekly by a physician, two nurses and a technician; management for
      emergencies was always warranted. Prothrombin time was carried out with a
      sensitive thromboplastin (ISI < 1.1) and a computer program provided calculation
      and graphical representation of INR, comparison with therapeutic range, automatic
      dosage prescription and print out. Laboratory quality of therapy was assessed by
      three different techniques: 'cumulative INR', 'last check in file' and 'linear
      change', yielding respectively 69% of laboratory controls, 71% of patients and
      80% of days within the therapeutic range. The rate of thrombosis, major and total
      bleeding were respectively 0.2%, 0.2% and 12.5%. An anticoagulation clinic
      represents an effective organizational model for the management of patients
      taking oral anticoagulants.

PMID- 8578516
TI  - Quality control and oral anticoagulation.
AB  - The introduction of the INR system for the monitoring of oral anticoagulant
      control represents a major advance, not only in terms of therapeutic efficacy but
      also in respect of patient safety. It is important to recognize that the system
      is only viable if careful attention is paid to the many important variables which
      contribute to its overall value. These include the choice of thromboplastin,
      assignation of ISI, determination of the mean normal prothrombin time and the
      method of end-point detection. Participation in independent external quality
      assessment schemes permits a unique opportunity for individual laboratories to
      identify, through laboratory performance analysis, problems relating to their own
      laboratory practice. Another major advantage, particularly of the larger schemes,
      is the identification of poor reagents and coagulometers and inconsistencies in
      their performance. One example of this is the recent identification of problems
      in respect of ISI assignment for thromboplastins used with coagulometers. This,
      in turn, provided the necessary stimulus to the potentially important development
      of calibrants for local ISI determination (21).

PMID- 8578517
TI  - The absence of the blood clotting regulator thrombomodulin causes embryonic
      lethality in mice before development of a functional cardiovascular system.
AB  - We have targeted the murine thrombomodulin (TM) gene in embryonic stem cells and
      generated embryos as well as mice with TM deficiency. The heterozygous TM
      deficient (TM+/-) mice as compared to wild-type (TM+/+) littermates exhibit 50%
      reductions in the levels of TM mRNA and TM protein. However, TM+/- mice appear
      normal and are free of thrombotic complications. The homozygous TM-deficient (TM
      /-) embryos die before E9.5. An overall retardation in growth and development of
      TM-/- embryos is first evident on E8.5 (8-12 somite pairs). However, no specific
      pathologic abnormalities are observed. These initial changes take place at a time
      when TM is normally expressed in the endoderm of the parietal yolk sac. The
      removal of E7.5 TM-/- embryos from maternal decidua and their subsequent culture
      in vitro allows development to proceed to stages not observed in vivo (13-20
      somite) with the appearance of normal blood vessels in the visceral yolk sac and
      embryo. The results of our studies suggest that the failure of TM-/- embryos to
      survive at mid-gestation is a consequence of dysfunctional maternal-embryonic
      interactions caused by the absence of TM in the parietal yolk sac and demonstrate
      that the receptor is necessary for normal embryonic development in utero.

PMID- 8578518
TI  - Thrombopoietin: the primary regulator of megakaryocyte and platelet production.
AB  - The development of blood cells requires the interplay of hematopoietic stem and
      progenitor cells, marrow stroma and polypeptide growth factors. Although many
      proteins support the expansion of megakaryocytic precursor cells, identification
      of the late acting, lineage specific growth factor for platelet production,
      termed thrombopoietin, has remained elusive. Recently, characterization of the
      proto-oncogene c-mpl revealed structural homology with the hematopoietic cytokine
      receptor family. Based on the cell of origin of its cDNA, we hypothesized that
      the ligand for c-Mpl might be identical with Tpo, and together with scientists at
      ZymoGenetics, Inc. recently cloned its cDNA. Using recombinant protein we have
      shown that the mpl-ligand displays all of the expected biological properties of
      the major regulator of megakaryocyte development, and proposed that it be termed
      thrombopoietin.

PMID- 8578519
TI  - c-mpl, the thrombopoietin receptor.
AB  - v-mpl is a mouse oncogene that is part of the genome of the myeloproliferative
      leukemia virus (MPLV). The cellular homolog gene c-mpl encodes an hematopoietic
      cytokine receptor mainly restricted to the megakaryocytic lineage of
      differentiation. Using the Mpl receptor protein, cDNAs corresponding to the
      receptor ligand were isolated in humans, pigs, dogs and mice. In vivo and in
      vitro, the recombinant molecule has both the thrombopoietin (TPO) and
      megakaryocyte-colony stimulating factor (MK-CSF) activities. This molecule (Mpl
      ligand/TPO/MK-CSF) seems to be the humoral physiological regulator of platelet
      production.

PMID- 8578520
TI  - Organization of the provisional fibronectin matrix: control by products of blood
      coagulation.
AB  - Assembly of fibronectin into the provisional fibrillar matrix of embryonic
      tissues and wounds is a complicated process by which the intracellular
      cytoskeleton determines the pattern of assembly of extracellular matrix and vice
      versa. Assembly is restricted to dimeric fibronectin molecules with intact N
      terminal modules and occurs at specialized cell surface sites. Cellular display
      of assembly sites is labile and requires that cells be under tension and have
      functional beta 1 integrins. Lysophosphatidic acid (LPA) an intermediate for de
      novo lipid biosynthesis and a product of platelet activation, is a powerful serum
      modulator of fibronectin assembly.

PMID- 8578521
TI  - Control of cell proliferation by heparan sulfate and heparin-binding growth
      factors.

PMID- 8578522
TI  - Assessment of factors important in atherosclerotic occlusion and restenosis.

PMID- 8578523
TI  - The three processes leading to post PTCA restenosis: dependence on the lesion
      substrate.

PMID- 8578524
TI  - LDL-platelet interaction under oxidative stress induces macrophage foam cell
      formation.
AB  - The atherosclerotic lesion consists of macrophages filled with cholesterol
      derived from oxidized-low density lipoprotein (Ox-LDL) and also contains platelet
      aggregates. Under oxidative stress on platelet activation, and enhanced
      macrophage uptake of Ox-LDL (secondary to platelet-mediated modification of the
      lipoprotein or to the interaction between Ox-LDL and arterial wall macrophages).
      The following data demonstrate that all of these mechanisms are operable in
      vitro: 1) upon platelet incubation with Ox-LDL, platelet aggregation and release
      are substantially increased; 2) under oxidative stress (in the presence of
      ferrous ions) platelets' phospholipids are oxidized, paralleled by increased
      platelets activation; 3) platelet conditioned medium (PCM) from collagen
      activated platelets, can modify LDL to a form which is taken up by macrophages at
      enhanced rate; 4) under oxidative stress (in the presence of copper ions)
      platelets can oxidatively modify native LDL; 5) PCM increases macrophage uptake
      of Ox-LDL, secondary to the stimulatory effect of PDGF (which is present in PCM)
      on the macrophage receptors for Ox-LDL. In conclusion, we suggest that the
      involvement of platelets in macrophage foam cell formation is related to platelet
      released factors which can either oxidize the LDL or increase the uptake of Ox
      LDL by the macrophages. These effects of platelets on Ox-LDL, as well as the
      activation of blood platelets by Ox-LDL, contribute to the formation of the
      atherosclerotic lesion.

PMID- 8578525
TI  - Advances in antithrombotic therapy: novel agents.
AB  - Most of the clinical evaluation of the direct thrombin inhibitors has been in
      coronary artery disease. The recent clinical reports suggest that there is a
      narrower window of safety with recombinant hirudin than initially thought
      particularly when it is used in conjunction with thrombolytic agents and aspirin
      in acute myocardial infarction. The efficacy data, however, indicate that the
      direct thrombin inhibitors have great potential particularly in the initial
      management of patients with acute unstable angina and non-Q-wave infarction.
      There is much to learn regarding the mechanism of action, optimal dose, and
      optimal concomitant therapy in the use of direct thrombin inhibitors in the
      management of acute coronary ischaemia; and since hirudin and other direct
      thrombin inhibitors have so much potential in the management of acute coronary
      ischaemia, it is critical that dose-finding studies be performed to determine
      safe regimens of these agents to allow their evaluation in large-scale trials
      with important clinical outcomes. The direct thrombin inhibitors have also shown
      to have promise in the prevention of deep vein thrombosis in high-risk surgical
      patients. There is limited clinical data on the other novel anticoagulants which
      are currently being developed.

PMID- 8578526
TI  - The vascular biology of heart and lung preservation for transplantation.
AB  - In spite of optimal organ preservation techniques, the heart and the lungs remain
      extremely vulnerable to the ischemia and reperfusion which accompany the
      transplantation procedure. Following a period of prolonged preservation, the
      altered phenotype of the graft vasculature results in vasoconstriction,
      neutrophil sequestration, edema, and thrombosis in the reperfused graft. These
      parameters of vascular dysfunction translate into primary graft failure and
      recipient demise. Using endothelial cells exposed to hypoxia and reoxygenation as
      a simple paradigm for the vascular milieu during organ
      preservation/transplantation, we have found that second messenger pathways (cAMP
      and NO/cGMP) are suppressed, neutrophil-endothelial interactions are enhanced,
      and prothrombotic mechanisms are activated. Using heterotopic rat heart and
      orthotopic rat lung transplant models, we have shown that supplemention of second
      messenger pathways or interference with neutrophil-endothelial interactions can
      significantly enhance preservation. Understanding mechanisms of vascular
      dysfunction within the graft should help define clinically relevant therapeutic
      targets to enhance heart or lung preservation for transplantation.

PMID- 8578527
TI  - The PAI-1/vitronectin interaction: two cats in a bag?

PMID- 8578528
TI  - The tissue factor pathway: how it has become a "prima ballerina".

PMID- 8578529
TI  - Plasminogen activator inhibitor 1 (PAI-1) in plasma: its role in thrombotic
      disease.
AB  - Impaired fibrinolytic function, mainly due to an elevation of the plasma PAI-1
      concentration, is a common finding in patients with thrombotic disease.
      Unfortunately, regarding patients with idiopathic deep vein thrombosis (DVT), no
      reliable prospective or genetic studies have been published. Concerning
      postoperative DVT, preoperatively increased PAI-1 level seems to predict a
      postoperative DVT in patients subjected to hip surgery. Several longitudinal
      cohort studies of patients with manifest coronary heart disease (CHD) have linked
      elevated plasma PAI-1 or tPA antigen concentrations to future cardiovascular
      events, particularly myocardial infarction. Before PAI-1 can be regarded as a
      risk factor in the conventional epidemiological sense, its relationship to
      myocardial infarction must be demonstrated in prospective studies of healthy
      populations. Regulation of the plasma concentration of PAI-1 is complex and at
      present not well understood. Multiple interactions with disturbances of both
      carbohydrate and lipoprotein metabolism are evident. Many studies have been
      carried out in cultured cells, but data can hardly be transformed into human
      pathophysiology. It seems that both environmental and genetic factors are of
      importance for the plasma PAI-1 concentration. Recently, knowledge of the
      importance of genetic factors involved in the regulation of plasma PAI-1
      concentration has become available. Interestingly, preliminary data suggest that
      the 4G/5G polymorphism located within the PAI-1 promoter is connected to CHD.
      More data on larger patient groups are needed and will certainly shed new light
      on the importance of impaired fibrinolytic function in the etiology of CHD in the
      near future.

PMID- 8578530
TI  - Thrombin generation in myocardial infarction and hypercholesterolemia: effects of
      aspirin.
AB  - Over the last few years methods have been developed to assess appearance of
      thrombin during blood clotting in a clinical setting. This can be achieved either
      by measurement of the specific thrombin markers or by analysis of the thrombin
      generation kinetics. Thrombin markers rise following coronary occlusion and,
      surprisingly, their plasma levels become further increased during and after
      thrombolytic treatment with streptokinase or tissue-plasminogen activator. In
      myocardial infarction enhanced thrombin generation extends over the weeks, well
      beyond the acute phase of the disease. It indicates increased risk to a patient
      and might call for more anticoagulation or angioplasty. The benefit of aspirin as
      conjunctive treatment for thrombolysis has been clearly demonstrated. The well
      founded concept is that aspirin exerts its anti-thrombotic action through
      inhibition of platelet cyclooxygenase. Recent evidence indicates that
      antithrombotic effects of aspirin might be explained, partly at least, by its
      inhibition of thrombin formation. Indeed, in both healthy subjects and survivors
      of myocardial infarction, aspirin, either at a single dose of 500 mg or at a dose
      of 300 mg per day administered over two weeks, effectively inhibits
      thrombinogenesis. Such response to aspirin is blunted in hypercholesterolemia.
      Subjects with high serum cholesterol levels might profit less than others from
      the anti-thrombotic action of aspirin.

PMID- 8578531
TI  - A review of mutations causing deficiencies of antithrombin, protein C and protein
      S.
AB  - The mutations observed in patients with antithrombin and protein C deficiencies
      are mostly substitutions of one nucleotide, or deletions/insertions of fewer than
      10 nucleotides in the exons and intron-exon junctions. These genomic
      abnormalities result in missense changes (involving aminoacids important for
      protein folding), aberrant polypeptide chains and/or premature termination
      codons, or abnormal splicing precluding DNA transcription. The number of
      mutations so far identified is such that it is difficult to use genomic DNA
      analysis for diagnostic purpose. However, identification of the gene defect can
      be useful in well-defined situations, such as the risk of homozygosity, and
      complex or ambiguous plasma phenotypes, which frequently occur in protein C
      deficiency. Protein S deficiency, the molecular bases of which have been less
      extensively studied, is due to micromodifications of the coding sequence in only
      half the cases investigated so far. The mechanisms involved in the remaining
      cases remain to be identified.

PMID- 8578532
TI  - Tissue factor pathway inhibitor.

PMID- 8578534
TI  - The skin: upholder of physiological homeostasis. A physiological and (bio)
      physical study program.

PMID- 8578533
TI  - Management of patients with hereditary defects predisposing to thrombosis
      including pregnant women.
AB  - In general, the current recommendations for treating and prophylaxing thrombotic
      patients with hereditary defects are similar to those for thrombotic individuals
      without a defect. Determinations as to the need for long-term anticoagulation
      require that a clinical assessment be made regarding the relative benefit in
      preventing thrombotic episodes versus the risk of increased bleeding. With our
      newly found ability to identify genetic risk factors in a substantial fraction of
      patients with venous thrombosis and pulmonary embolism, it will be possible to
      perform rigorously designed studies to determine whether they should be managed
      with more prolonged or intense anticoagulation after a thrombotic event or more
      aggressive prophylactic regimens in high risk situations such as a total hip
      replacement.

PMID- 8578535
TI  - Megakaryocyte growth and development factor (MGDF) moderately enhances in-vitro
      platelet aggregation.
AB  - Megakaryocyte growth and development factor (MGDF) is a novel cytokine which
      promotes the development of immature megakaryocytes into platelets. We tested the
      hypothesis that MGDF would alter the sensitivity of platelets to aggregating
      agents as assessed by in-vitro platelet aggregometry. Platelet aggregation in the
      presence or absence of MGDF was tested with single doses of clinically relevant
      aggregating agents. A dose-dependent enhancement of the aggregation response to
      epinephrine was noted in MGDF treated platelets. When a range of concentrations
      of ADP were used to generate an aggregation dose-response curve, the addition of
      MGDF to platelet rich plasma shifted the dose response curve to the left. The
      effect of MGDF on platelet aggregation was partially prevented by the
      coincubation of platelets with a soluble form of the receptor for MGDF, the
      extracellular domain of c-mpl. In addition, we demonstrate that exogenous MGDF is
      able to induce tyrosine phosphorylation of platelet proteins with apparent
      molecular weights of 85 kDa and 130 kDa. From these data we conclude that
      exogenously added MGDF moderately increases the sensitivity of platelets to
      aggregating agents through a mechanism which appears to involve tyrosine
      phosphorylation of platelet proteins.

PMID- 8578536
TI  - Binding of prothrombin to chyle chylomicrons: effects of temperature and calcium
      ions, and role of surface phospholipids.
AB  - The ability of chyle chylomicrons to bind prothrombin has been studied. Rat chyle
      chylomicrons were incubated with human 125I-prothrombin and binding was examined
      by separating the chylomicrons from free 125-I-prothrombin by density-gradient
      ultracentrifugation, and by gel filtration on Sepharose CL-2B. A significant
      binding of prothrombin to chyle chylomicrons occurred. The complex formation was
      calcium dependent, and decreased markedly when the temperature was lowered from
      37 degrees C to 20 degrees C and when PH was raised above 8. The time course for
      the binding at 37 degrees C in presence of 2 mmol/L CaCl2 exhibited an initial
      lag phase at about 10 minutes. Thereafter most of the binding occurred within 30
      minutes. Bound prothrombin could not be removed from chyle chylomicrons by
      treatment with EDTA, suggesting that this binding is not a simple Ca2+ dependent
      association between prothrombin and chyle chylomicrons. Inclusion of 1% purified
      human serum albumin caused a 50% decrease in binding, half of which was reversed
      by increasing the Ca2+ ion concentration. Addition of pancreatic phospholipase A2
      (PLA2) in doses sufficient to hydrolyze more than 95% of the
      phosphatidylethanolamine (PE) and 37% of the phosphatidylcholine (PC) decreased
      the binding by 50%. Doses of PLA2 that hydrolyze more than 95% of the
      phosphatidylethanolamine (PE) and 37% of the phosphatidylcholine (PC) decreased
      the binding by 50%. Doses of PLA2 that hydrolyzed 60-80% of (PE and 4-10% of the
      PC decreased the binding by only 7-15%. It is suggested that the binding of
      prothrombin to chyle chylomicrons is in part mediated by negatively charged
      phospholipids of the chylomicron surface, although a specific role of the PE
      could not be demonstrated.

PMID- 8578537
TI  - Retinoic acid enhances plasminogen activation on the cell surface.
AB  - The importance of cell-associated plasminogen activation in the extracellular
      matrix degradation processes is becoming increasingly evident. To elucidate the
      modulators of net plasminogen activation on the cell surface, we have recently
      established an assay system. Using this system, we examined the effects of
      several candidate modulators on cell surface plasminogen activator in the human
      fibrosarcoma cell line HT-1080 and the SV40-transformed human lung fibroblast
      cell line WI-38 VA 13 2RA. Although the majority of the candidates had no effect
      or a selective effect on either cell line, only retinoic acid markedly enhanced
      cell surface plasminogen activator activity in both HT-1080 and WI-38 VA13 2RA
      cells in a time-dependent manner. The effect of retinoic acid was neutralized by
      actinomycin D. The enhanced activity was inhibited by anti-uPA IgG and by
      pretreatment with phosphatidylinositol-specific phospholipase C. These findings
      suggest that retinoic acid increases the amount of receptor-bound uPA via de novo
      synthesis, and that it plays an important role in modulating cell-associated
      plasminogen activation.

PMID- 8578538
TI  - The normalization period of platelet aggregation in newborns.
AB  - This study was performed to investigate the normalization period of the transient
      platelet dysfunction of newborns. A total of 43 healthy newborns of healthy
      mothers who had received no medication for at least 14 days prior to delivery
      were included in the study. Venous blood samples of 44 healthy volunteer adults
      were used as control. Platelet aggregation study was performed in whole blood by
      impedance aggregometry. Collagen or ADP was used as the aggregating agent. In the
      platelet aggregation studies using collagen, maximum aggregation values in the
      first three days of life were lower than those of adults (p < 0.001). These lower
      values were improved and reached adult values between the 5th and 9th day of
      life. Lower maximum aggregation values were observed in newborns in comparison
      with those of adults when ADP was used, but the difference was not significant
      except for 5 microM concentration of ADP. There was no significant difference
      between the aggregation time of the collagen and ADP groups (p > 0.05). In
      conclusion, the platelet responses to ADP and collagen were increased in newborns
      as the age progressed and reached normal levels between 5th and 9th day of life.
      If platelet dysfunction does exist after the 10th day of life, this finding may
      be due to either simple prolongation of the physiological phenomenon or platelet
      disorders.

PMID- 8578539
TI  - Evidence for competition between vitamin K-dependent clotting factors for
      intracellular processing by the vitamin K-dependent gamma-carboxylase.
AB  - This study demonstrates an apparent competition between newly synthesized
      precursors of prothrombin and factor X for binding to and processing by the gamma
      carboxylase in the ER membrane of hepatocytes. The precursor of factor X appears
      to exhibit a strong affinity for the carboxylase than the prothrombin precursor.
      This conclusion is supported by the findings that 1) in normal hepatocytes, the
      factor X precursor prevents increased prothrombin precursor binding to the ER
      membrane, 2) increased prothrombin binding to the ER membrane was measured in H4
      II-E-C3 Reuber H-35 cells where factor X synthesis is suppressed. The variations
      in the concentrations of the prothrombin and the factor X precursors that were as
      associated with the ER membrane correlated with the available prothrombin and
      factor X substrate pools for the gamma-carboxylase.

PMID- 8578540
TI  - Effects of various fatty acids alone or combined with vitamin E on cell growth
      and fibrinogen concentration in the medium of HepG2 cells.
AB  - Dietary intake of fish oils, rich in the polyunsaturated fatty acids (PUFAs)
      docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has given
      inconsistent results as to their influence on the plasma fibrinogen level (1, 2,
      3, 4, 5, 6). In the present study we have examined the effects of various fatty
      acids, the PUFAs and the saturated fatty acid palmitic acid (PA), alone or
      combined with the antioxidant vitamin E (Vit.E), on the fibrinogen concentration
      in the growth medium of human hepatoma (HepG2) cells. Vit.E alone decreased the
      amount of fibrinogen in the medium in a dose dependent fashion, where fibrinogen
      was measured as Fibrinopeptide A (FPA) releasable by thrombin. EPA and Vit.E
      decreased the amount of fibrinogen additively. PUFAs alone increased the
      fibrinogen concentration in a dose dependent manner. PUFAs combined with a fixed
      dose of Vit.E decreased the fibrinogen concentration, also dose dependently. OA
      and PA had an inhibitory effect, both alone and combined with Vit.E. These
      results indicate that Vit.E may be necessary for PUFAs to have a fibrinogen
      lowering effect, whereas both OA and PA apparently may decrease the fibrinogen
      concentration in the cell medium of HepG2 cells, both alone and combined with
      Vit.E. Possibly, peroxidation of the PUFAs may increase the fibrinogen
      production, that may be counteracted and reversed by the simultaneous presence of
      Vit.E.

PMID- 8578541
TI  - Pooled patient samples as reference material for D-Dimer.
AB  - A low-D-Dimer concentration has a high negative predictive value for
      thromboembolic events. Actual and proposed applications include exclusion
      diagnosis of DIC, DVT and pulmonary embolism (1-7), follow up of cancer therapy
      (8) and diagnosis of abruptio placentae(9). A variety of tests are commercially
      available. Unfortunately, due to differences in standardization protocols, the
      cut-off normal/pathological of one test can usually not be used for another(10).
      As was shown by Nieuwenhuizen, one way to at least reduce these discrepancies is
      to use patient material as a reference(11). We have used this approach to
      standardize the latex test Tinaquant a D-Dimer against the ELISA test Asserachrom
      D-Dimer.

PMID- 8578542
TI  - D-Dimer in intra-uterine growth retardation and gestational hypertension.
AB  - Pregnancy is sometime related to thromboembolic complications (1) and alterations
      in different hemostatic parameters have been reported in pregnancy (2-4). In
      particular, a progressive increase in fibrinogen and D-dimer levels occurs during
      normal pregnancy (5-9). D-dimer levels may be predictive for some complications
      such as preeclampsia (10) and they have been also reported to be useful for
      diagnosis of abruptio placentae (6). However, it remains to be established if
      common ELISA for D-dimer are able to discriminate pathologic samples in
      conditions such as intrauterine growth retardation (IUGR) or gestational
      hypertension (GH). Aim of the present study has been to evaluate the behavior of
      D-dimer in pregnant women with IUGR and GH.

PMID- 8578543
TI  - Effective anticoagulation by argatroban during immunoadsorption therapy for
      malignant rheumatoid arthritis with a high polymorphonuclear leukocyte elastase
      level.
AB  - Polymorphonuclear leukocyte elastase (PMNE) is a glycoprotein with a molecular
      weight of about 30000 and exists in 3 isozymes (1). It has a biological role in
      host defense mechanisms, but it sometimes induces abnormal blood coagulation and
      injury of the vascular intima (1,2). We were not able to obtain a satisfactory
      anticoagulant effect when using heparin during immunoadsorption therapy in a
      patient with malignant rheumatoid arthritis and high PMNE level, but found that
      argatroban, a selective antithrombin agent, produced satisfactory
      anticoagulation. This finding is interesting as far as the various pathologic
      roles of PMNE are attracting increasing clinical attention (1,2,3).

PMID- 8578544
TI  - Species differences in anticoagulant and anti-Xa activity of DX-9065a, a highly
      selective factor Xa inhibitor.
AB  - Activation of the blood coagulation cascade results in the formation of factor Xa
      (FXa) in either its intrinsic or extrinsic pathways, which in turn converts
      prothrombin to thrombin. We recently described the synthesis and characterization
      of DX-9065a, a highly selective FXa inhibitor, as an orally active anticoagulant
      agent (1). Although DX-9065a potently inhibited human FXa (2), a much larger
      dosage was required to inhibit thrombus formation in a rat thrombosis model (3):
      The plasma concentration of DX-9065a after administration of a dose which reduced
      thrombus formation by 50% in rats was in the microM range, or 40 times higher
      than the Ki value for FXa. From this, several assumptions arise, namely that an
      unknown mechanism other than FXa inhibition contributes to the antithrombotic
      effect of DX-9065a, or that the efficacy of DX-9065a differs among species.
      However, as the anticoagulant effect of DX-9065a was closely consistent with anti
      Xa activity in plasma and as DX-9065a inhibited only FXa activity (2), the former
      assumption could be disregarded. To clarify the latter, we examined the
      inhibitory effect of DX-9065a on FXa from several animal species and its
      anticoagulant effect ex vivo in these species. Further, we also compared the
      anticoagulant effect of DX-9065a in plasma from each species with that of NAPAP,
      a benzamidine-derived direct thrombin inhibitor (4).

PMID- 8578545
TI  - Some functional properties of teleost antithrombin.
AB  - Antithrombin from bony fish (Teleostei), represented by an ancient salmonid,
      Atlantic salmon (Salmo salar L.), and a more evolved species from the same
      family, rainbow trout (Oncorhynchus mykiss Walbaum), functions in vitro as does
      its human counterpart: it inactivates thrombin almost instantaneously in the
      presence of heparin and only slowly when heparin is absent. The inhibitory
      activity of salmonid antithrombin towards the homologous thrombin did not differ
      noticeably from its inactivating capacity in heterologous (teleost) systems, and
      enzyme-inhibitor reactions between reagents from fish and man proceeded just as
      efficiently. In all enzyme-inhibitor reactions with salmonid thrombin the
      inactivation by salmonid antithrombin or diluted fish plasma was maximal at pH
      7.8-8.4. The inactivation was clearly dependent on heparin in all systems and
      maximal at concentrations between 1.5 and 6 U/ml. What particularly distinguishes
      the salmonid thrombin-antithrombin interaction from the human one is that the
      former has to function over a wide range of temperatures. And the thrombin
      inactivating capacity of purified antithrombin and diluted plasma in the presence
      of heparin was indeed present at temperatures down to 3 degrees C, a capacity
      that human antithrombin also has retained. Even more interesting was that the
      teleost enzyme-inhibitor reaction was nearly independent of temperature under the
      conditions studied.

PMID- 8578546
TI  - Effects of antithrombin III (AT III) and Trp49-modified AT III on plasma level of
      6-keto-PGF1 alpha in rats.
AB  - We evaluated the effect of antithrombin III (AT III) on the plasma level of 6
      keto-PGF1 alpha in rats to determine whether AT III may promote the release of
      prostacyclin (PGl2) from endothelial cells in vivo. The intravenous
      administration of AT III (250 U/kg) significantly increased the plasma levels of
      6-keto-PGF1 alpha, with a peak seen 90 min post-administration. Neither Trp49
      modified AT III, which lacks affinity for heparin but retains an inhibitory
      capacity for thrombin, nor heparin plus AT III, increased the plasma level of 6
      keto-PGF1 alpha 90 min after administration. Indomethacin pretreatment inhibited
      the increase in plasma levels of 6-keto-PGF1 alpha produced by AT III.
      Observations suggest that AT III may promote the release of PGl2 from endothelial
      cells by interacting with heparin-like glycosaminoglycans in vivo, consistent
      with previous observations in cultured endothelial cells.

PMID- 8578547
TI  - Anti-platelet effects of clopidogrel in rat middle cerebral artery thrombosis
      model.
AB  - We have developed a model whereby the middle cerebral artery (MCA) in an
      experimental animal can be occluded by photochemical reaction between rose bengal
      and green light which causes endothelial injury followed by platelet adhesion,
      aggregation and formation of a platelet and fibrin-rich thrombus at the site of
      photochemical reaction. Using this model, we investigated the effect of
      clopidogrel, an analogue of ticlopidine which is a potent inhibitor of adenosine
      5'-diphosphate (ADP)-induced platelet aggregation. Oral clopidogrel (3-10mg/kg)
      inhibited ex-vivo platelet aggregation induced by ADP, thrombin or the
      thromboxane A2 mimetic, and U46619, when platelets had been primed with low
      concentration of phorbol myristate acetate. At these doses, clopidogrel
      significantly (P < 0.001) prolonged the time to produce thrombotic occlusion of
      the MCA and induced a significant (P < 0.001) reduction in the size of ischaemic
      cerebral damage examined 24 hours after photochemical reaction. The results
      suggest that ADP has a key role in the thrombotic occlusion of the MCA in this
      model. Clopidogrel may be beneficial in the prevention of arterial thrombosis.

PMID- 8578548
TI  - Role of tissue factor in disseminated intravascular coagulation.
AB  - We examined plasma antigen levels of tissue factor (TF) in 95 cases of
      disseminated intravascular coagulation (DIC), to investigate the role of TF in
      DIC. A significant elevation of plasma antigen levels of TF was observed in cases
      of DIC associated with cancer. However, no such significant elevation was
      observed in cases of DIC associated with acute promyelocytic leukemia (APL),
      acute leukemia except APL, blastic crisis of chronic myelogenous leukemia, non
      Hodgkin lymphoma (NHL), sepsis or fulminant hepatitis. No significant elevation
      of TF was observed in patients without DIC, except 4 cases of cancer who
      developed DIC thereafter. Plasma antigen levels of TF were higher in both cases
      of DIC with renal failure and chronic renal failure without DIC than its levels
      in those without renal failure. Therefore, plasma antigen levels of TF in DIC
      patients with renal failure were considered to be carefully estimated. The levels
      of TF were decreased with the clinical improvement in some cases of DIC but were
      further increased or remained at high levels in patients who showed no
      improvement of DIC. Thus, plasma antigen levels of TF is an important marker to
      predict the development and/or prognosis of DIC, especially in patients with
      cancer.

PMID- 8578549
TI  - Platelet disorders in uraemia before and after haemodialysis under the influence
      of low dose aspirin.
AB  - Thrombocyte dysfunction and increased bleeding time (BT) are well documented in
      uraemic patients. However, these patients are frequently medicated with low dose
      aspirin (ASA) in order to maintain shunt patency and prevent cardiovascular
      events. Recently, life- threatening gastrointestinal haemorrhage in an uraemic
      subject taking low dose aspirin has been reported. In this work ASA related
      bleeding risk in uraemic patients and the effect of haemodialysis on their
      bleeding tendency was studied by measuring in vitro bleeding time (BT) using the
      Thrombostat 4000 in 34 uraemic patients on chronic haemodialysis compared to 50
      healthy subjects. Our results indicate that low dose aspirin does not influence
      uraemic thrombopathia 8 to 10h after ingestion but seems to increase bleeding
      risk shortly after ingestion. Moreover, haemodialysis alters uraemic in vitro BT
      with regard to the time after ingestion of ASA.

PMID- 8578551
TI  - Effects of chemical modifiers on recombinant factor VIII activity.
AB  - Factor VIII performs a critical role in the blood coagulation cascade but is
      extremely labile. We have carried out chemical studies on a fully functional
      recombinant Factor VIII (rFVIII) using a variety of protein modifying agents,
      some of which were bifunctional. Thiol-specific maleimides cause no activity loss
      despite a substantial decrease in rFVIII's free thiol content. Mild oxidation
      procedures had either neutral or adverse effects on activity. Amino-specific
      reagents led to significant losses of rFVIII procoagulant activity. It appears
      that free amino groups are essential for Factor VIII's function while some at
      least of its many free thiol groups are not. None of these derivatives was any
      less labile than unmodified rFVIII. Systematic chemical modification of important
      proteins in this way can give useful insights into appropriate protein
      engineering strategies.

PMID- 8578550
TI  - N' alkylamine low molecular mass heparins (LMM-heparin-tyramine and LMM-heparin
      tyramine-fitc) exhibit long lasting anticoagulant effects.
AB  - The pharmacodynamic and pharmacokinetic properties of endpoint-attached
      N'alkylamine derivatives of low molecular mass heparin (LMMH), low molecular mass
      heparin (LMMH), low molecular mass heparin-tyramine (LMMH-tyr) and low molecular
      mass heparin-tyramine-fluorescein-5-isothiocyanate (LMMH-tyr-fitc) were
      investigated ex vivo. After intravenous bolus injection of LMMH, LMMH-tyr and
      LMMH-tyr-fitc (150 aXa U/kg) to Sprague-Dawley rats (n = 8), LMMH-tyr and LMMH
      tyr-fitc displayed decreased clearances. The beta-half-life time of the
      antifactor Xa (aXa) of "endpoint-attached heparins" was significantly prolonged:
      LMMH-tyr (125 min), LMMH-tyr-fitc (141 min) compared to LMMH (69 min). The
      pharmacokinetics of LMMH-tyr-fitc were measured with reversed phase high
      performance liquid chromatography (RP-HPLC). It showed a decreased clearance and
      a prolonged half-life time (132 min). The selectively tagged LMMH-tyramine and
      LMMH-tyramine-fitc may be used to investigate the pharmacokinetics, plasma
      protein and cellular binding of low molecular mass heparins.

PMID- 8578553
TI  - Responsiveness of atiii and coagulation factors V and VII to a standardized oral
      fat load.

PMID- 8578552
TI  - Coagulation assay with improved specificity to factor V mutants insensitive to
      activated protein C.
AB  - The prevalence of a new hereditary defect in the protein C anticoagulant pathway,
      the factor V-Leiden, has been reported to range between 20% to 60% in familial
      thrombophilia. In addition to differences in patient groups, these very divergent
      numbers might also be due to the detection method applied. In most studies a
      modified APTT was used, where activated protein C (APC) is added simultaneously
      with the start of the clotting reaction. However, this method is also influenced
      by other factors like protein S, factor VIII or lupus anticoagulants.
      Furthermore, heparin or oral anticoagulant therapy might interfere. We tried to
      develop a coagulation assay dependent only on those mutant forms of factor V
      stable against proteolytic attack by APC. For this purpose, samples were first
      diluted with a factor V deficient plasma (f.V-dp). Then, coagulation was
      initiated either on the intrinsic pathway (APTT) or on the extrinsic pathway (PT)
      or, by directly activating factor X (RVVT). Additionally, APC was added, which
      prolongation of the clotting time. Deficiencies in protein S or the presence of
      factor V-Leiden resulted in a less pronounced clotting time prolongation.
      Titration of protein S-deficient plasma samples with f.V-dp diminished this
      effect. In contrast, in samples with factor V-Leiden the difference to the
      clotting time obtained with normal plasma even increased in the order
      APTT>>RVVT>PT. In the APTT-based method high concentrations of factor VIII
      shortened the clotting times, thus mimicking a factor V-Leiden defect. This could
      be compensated for up to 4 U/ml factor VIII by using a f.V-dp containing factor
      VIII at physiological concentration. Neither unfractionated nor LMW-heparin (up
      to 2 U/ml) interfered with the determination. In a brief investigation on 16
      plasma samples from patients under oral anticoagulation 5 (30%) showed a similar
      behaviour as observed with normal plasma from factor V-Leiden carriers. These
      results let us suggest that by simply mixing the patient sample with a factor V
      deficient plasma factor V-Leiden might be detected also in patients under oral
      anticoagulant therapy. Inherited disorders of protein C or protein S are well
      known as thrombotic risk factors (1). The recent investigations by Dahlback et
      al. (2) led to the discovery of a new hereditary defect in the protein C
      anticoagulant pathway: the factor V-Leiden (3). This mutation renders activated
      factor V stable against proteolytic attack by activated protein C (APC). The
      reports on the prevalence of this mutation in thrombophilic patients show a
      considerable variation between 21% (4) and 64% (5).(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8578554
TI  - An improved method for separation of neutrophils from human blood using
      methylcellulose.

PMID- 8578555
TI  - Relationships between the nuclear membrane, nuclear pore complexes, and
      organelles in the type II pneumocyte.
AB  - Functional relationships among organelles of the type II cell are suggested based
      upon the proximity of organelles to specialized areas of the plasma- and nuclear
      membranes. In a two-dimensional morphometric analysis of the profiles of
      organelles in type II cells of the ferret and rat (and beagle dog), lamellar
      bodies were more likely to be located near the nuclear membrane than at the
      alveolar space (where exocytosis occurs). The size of lamellar body profiles was
      not correlated with distance from the nuclear membrane; however, large profiles
      were nearer the apical membrane, and smaller ones nearer the basement membrane.
      Profiles of highly branched mitochondria were 10 times more frequently associated
      with nuclear pore complexes than with the inter-pore nuclear membrane. Forty
      percent of all mitochondrial profiles were within 0.25 microns of the nucleus, 5%
      were within 0.02 microns and half of these appeared to touch the filaments of the
      nuclear pore complexes. The size of mitochondrial profiles was not correlated
      with distribution. In the ferret and rat, 8.6% and 2.5% respectively, of the
      nuclear pore complexes were associated with mitochondria. Sebaceous cells, from
      control mice, demonstrated a spatial distribution of granules which was size
      dependent but unrelated to the nuclear membrane.

PMID- 8578556
TI  - Apical polarity in human colon carcinoma cell lines.
AB  - The non-polar human adenocarcinoma cells (HT29) when grown as monolayers or
      aggregates, have no tight junctions and no brush border. When these cells are
      treated with forskolin (15-100 microM) or cholera toxin (1 nM) intercellular
      lumina appear between the cells and about 30% of the cells facing the medium or
      the lumina are fully covered with a brush border. Aggregates embedded in collagen
      type I and treated with forskolin form a brush border only on cells facing the
      intercellular lumina. Monolayers of the polar human colon adenocarcinoma cell
      line Caco-2 express spontaneously tight junctions and a brush border in all the
      cells. When grown in aggregates the inner cells lose their polarity and only the
      cells facing the medium are polar. This polarity was not found when the
      aggregates were embedded in collagen gels. Aggregates embedded in collagen and
      treated with forskolin form bubble-like structures with a single layer of polar
      cells facing a central lumen. The data indicate that cell polarity is probably
      controlled by both internal factors such as cAMP and external factors such as
      cell-cell and cell-substratum molecules.

PMID- 8578557
TI  - Tolerance to osmotic shocks in rats kidney cortex and medulla.
AB  - Kidney medulla cells of mammals have to cope with large changes in environmental
      osmolarity, a challenge most other mammalian cells never have to experience. In
      these last cells, application of osmotic shocks induces dramatic modifications in
      chromatin organization. The present paper reports on the changes of medulla cell
      chromatin in situ, in rat kidney slices submitted to osmotic challenges and in
      vitro, on preparations of extracted chromatin submitted to changes in
      environmental ion concentrations. Our results show that the chromatin of kidney
      medulla cells: (1) does not behave differently from the other mammalian
      chromatins when submitted in situ or in vitro to osmotic challenges; (2) presents
      in vitro physico-chemical characteristics similar to those of the other mammalian
      chromatins; and (3) is protected in vitro, as the other mammalian chromatins,
      from the disrupting effects of increases in inorganic ion concentrations by
      different compensatory organic solutes. The ability of kidney medulla cells to
      adapt to large increases in osmolarity could thus be related to a rapid control
      of the level of such compounds rather than to some rather specific, intrinsic
      molecular adaptations of macromolecules.

PMID- 8578558
TI  - Effect of high osmolarity acclimation on tolerance to hyperosmotic shocks in L929
      cultured cells.
AB  - Application of abrupt, large hyperosmotic shocks induces in L929 cultured cells
      changes similar to those previously described in other cell types, notably a
      hypercondensation of the nuclear chromatin. This paper shows that; 1) this
      phenomenon is concomitant with a complete disappearance of deoxyribonucleic acid,
      as visualized by immunogold labelling, from the nucleoplasmic spaces; 2)
      acclimation to high osmolarities (600 mOsm) by addition to the culture medium of
      NaCl, sorbitol or proline protects the cells from these effects, which appear to
      be largely attenuated-acclimated cells also survive much better to the osmotic
      shock than do control cells and; 3) the best protection seems to be provided by
      sorbitol and NaCl. Proline acclimation is less effective. These effects are
      discussed in terms of increased tolerance to NaCl load induced at the level of
      different macromolecules by so-called 'compensatory' organic compounds.

PMID- 8578559
TI  - Signs of aging are apparent in the testis interstitium of Sprague Dawley rats at
      6 months of age.
AB  - The present study investigated the effects of aging in the testis interstitium in
      Sprague Dawley rats. Rats of 3, 6 and 24 months of age were used. Testes of rats
      (n = 5) were fixed by whole body perfusion using a fixative containing 2.5%
      glutaraldehyde in cacodylate buffer, processed and embedded in eponaraldite.
      Using 1 microns sections stained with methylene blue, qualitative and
      quantitative morphological studies were performed. Purified Leydig cell
      preparations, obtained by collagenase digestion followed by elutriation and
      density gradient centrifugation, were used to determine luteinizing hormone (LH;
      100 ng/ml) stimulated testosterone secretory capacity per Leydig cell in vitro.
      Testosterone levels in the incubation medium, and testosterone and luteinizing
      hormone levels in serum of these three groups of rats were determined via
      radioimmunoassay. Morphological studies revealed that Leydig cells were more
      abundant in the testis interstitium at 6 and 24 months when compared to 3 months.
      Moreover, collagen fiber bundles were more frequently observed in the testis
      interstitium at older ages. Blood vessels of the testis interstitium in 24-month
      old rats frequently showed partial and complete occlusion of their lumen and
      thickening of vessel walls. This feature was also present at 6 months, but less
      frequently. The results of the stereological studies revealed that the volumes of
      seminiferous tubules, interstitium and Leydig cells per testis was significantly
      higher (P < 0.05), at 6 and 24 months of age than those at 3 months. Moreover,
      volume of macrophages per testis was observed to be significantly higher (P <
      0.05) at 6 months when compared to 3 and 24 months, and volume of connective
      tissue cells per testis was observed to be significantly lower (P < 0.05) at 6
      and 24 months when compared to 3 months of age. No significant difference (P >
      0.05) was observed for the volume of lymphatic space per testis in the three age
      groups studied. Volume of interstitial blood vessels per testis was not
      significantly different at 3 and 6 months of age, but a significantly greater (P
      < 0.05) volume was observed at 24 months. However, at 6 and 24 months, only 71%
      and 31% of the total blood vessel volumes respectively had completely open lumen
      in them; the rest of the blood vessels were either partially (12.5% at 6 months
      and 17% at 24 months) or completely (16.5% at 6 months and 52% at 24 months)
      occluded. The number of Leydig cells per testis was doubled at 6 and 24 months of
      age compared to 3 months. The average volume of a Leydig cell was not
      significantly different between 3 and 6 months of age, however, at 24 months a
      significantly lower (P < 0.05) value was observed. LH stimulated testosterone
      secretory capacity per Leydig cell in vitro was reduced by 50% at 6 months of age
      compared to 3 months; a further significant (P < 0.05) reduction was observed at
      24 months. Serum testosterone and LH levels were not significantly different
      between 3 and 6 months of age but at 24 months a significantly lower (P < 0.05)
      value was observed for both of these hormones. In summary, the present study
      demonstrated many changes in the components of the testis interstitium in the
      aged Sprague Dawley rat. Modifications in the blood vessels and the occurrence of
      abundant collagen fibers in the interstitial space could possibly contribute to
      the reduced testosterone secretory capacity per Leydig cell with advancing in
      age. The observed Leydig cell hyperplasia could be suggested as a compensatory
      effort to maintain the normal androgen status of the aged rat, which is rather
      successful at 6 months but unsuccessful at 24 months. This investigation further
      revealed that these characteristic changes in the aged testis interstitium at 24
      months are also present to some extent at 6 months of age in Sprague Dawley rats,
      suggesting that aging of the testis in this strain of rats commences early in
      life.

PMID- 8578560
TI  - Extracellular and intracellular degradation of collagen by trophoblast giant
      cells in acute fasted mice examined by electron microscopy.
AB  - The fine structure of trophoblast giant cells and their interaction with collagen
      at the antimesometrial region on the 9th day of pregnancy was examined in fed and
      acute fasted mice. Collagen fibrils and filamentous aggregates (disintegrating
      collagen fibrils) were observed in the extracellular space. Three types of
      intracellular vacuoles containing collagen fibrils were present: vacuole type A
      exhibited typical cross-banded collagen immersed in finely granular electron
      translucent material; and vacuoles type B and C showed electron-opaque granular
      material containing, respectively, faint cross-banded collagen and narrow clear
      stripes often with faint periodicity. In fed animals vacuoles type B were absent
      and the others were less evident. Only fasted animals showed extracellular acid
      phosphatase activity on collagen fibrils, filamentous aggregates and confined
      regions of the extracellular space. Intracellular acid phosphatase activity was
      observed in vacuoles type B and in lysosomes. The results indicate that
      trophoblast giant cells are capable of breaking down extracellular collagen and
      also of internalizing collagen for intracellular degradation. It is likely that
      these events are part of the process of invasion of the uterine wall. However, in
      fasted mice, collagen breakdown is more pronounced, and it may therefore
      contribute to the provision of amino acids and other nutrients for the
      undernourished fetus.

PMID- 8578561
TI  - [Hypoproteinemia].

PMID- 8578562
TI  - [Boredom in zoo animals--an relevant animal welfare problem?].
AB  - Modern sciences, the philosophy of insight, and psychology are the basis for a
      discussion of the question, whether animals can experience boredom or even suffer
      from it. Various examples are used for illustration. The results show that
      neither a direct statement is possible nor can a logical conclusion by indirect
      analogy be made.

PMID- 8578563
TI  - [Clinical case. Chronic abscessed pyogenic mastitis].

PMID- 8578564
TI  - [C-reactive protein as a new parameter of mastitis].
AB  - The C-reactive protein (CRP) is an acute phase protein. Its deposit can be seen
      on several animal species. Following the development of a test system (enzyme
      immunoassay/EIA) for the quantitative determination of bovine CRP, it was
      possible to detect this protein in bovine raw milk for the first time. It was
      shown in the first extensive investigations that the CRP concentration in raw
      milk was increased, sometimes as much as tenfold as a result of udder
      inflammation (mastitis). In several screening analyses of a herd of cows, the CRP
      values were compared with the somatic cell number, fat, protein and lactose
      content. The degree of CRP concentrations in raw milk in cows suffering from
      mastitis during the antibiotic treatment was reflected in the treatment success.
      When CRP was used as an additional parameter of selection, a better average udder
      health could be seen after five months. The first results of our investigations
      demonstrate that CRP is a practicable indicator of inflammation and may be
      effectively used to determine and control udder illness in cows.

PMID- 8578565
TI  - [Effects of dehydration on functional parameters of fluid balance as well as
      effectiveness of rehydration using crystalline or colloidal infusion drips in
      calves].
AB  - Studies were conducted on 57 calves (aged 3-23 d) to elucidate the effects of
      diarrhoeal and experimentally induced dehydration upon functional parameters of
      the fluid balance and of renal functionality. Aggravating intensity and length of
      diarrhoea was found to be accompanied by decline in intravasal and extracellular
      fluid compartments. Ante mortem dehydration of the animals with diarrhoea was
      close to 20% relative to body weight. This was paralleled by life-threatening
      drop of glomerular filtration rates to < 10% of original physiological values.
      Administration of a diuretic, associated with reduction by 50% of daily liquid
      uptake, proved helpful in generating dehydration of 5 to 6% relative to body
      weight. Evidence was provided to the effect that isooncotic colloid-electrolyte
      solution was superior to pure isotonic electrolyte solution for rehydration of
      calves dehydrated in the first place in the way described. Colloidal infusion, in
      particular, produced favourable therapeutic effects in terms of optimization of
      blood plasma volume and renal ultrafiltration.

PMID- 8578566
TI  - [Right displacement of the abomasum in cattle. 1. Pathogenesis, clinical course
      and prognosis].
AB  - A report is given about 462 cases (1989-1994) of abomasal displacement (RDA, n =
      275) and abomasal volvulus (AV, n = 187) in cattle. The pathogenesis and the
      functional disturbances of abomasal hypotony, displacement, and volvulus are
      described. A right and dorsally displaced abomasum easily performs an additional
      rotation around a vertical axis. In 99% of all cases this rotation is performed
      to the left (counter-clockwise, seen from rear) and the duodenum twines round the
      abomasal fundus, where it is compressed and trapped between the abomasum and the
      omasum. The intestinal passage becomes obstructed. As long as the abomasal twist
      does not exceed 180 degrees, functional disturbances are caused mainly by a
      reduced abomasal outflow, resulting in dehydration and in disturbances of blood
      acid-base-balance (hypochloremic alcalosis). These cases have a very good
      prognosis (success of treatment 91.3%), when surgery is performed immediately.
      When the twist of the abomasum exceeds 180 degrees (abomasal volvulus), the twine
      gets more contracted, strangulating the abomasal nerves and blood vessels.
      Serious cases like this (n = 136) were treated successfully in 64.7%. When the
      abomasal volvulus is complicated by an omasal (RDAO, n = 31) or an omasal and
      reticular involvement (RDAOR, n = 20) the success of therapy decreases to about
      40%.

PMID- 8578567
TI  - [Ultrasonographic findings of perivascular jugular vein diseases in cattle].
AB  - Ultrasonographic examinations were used to characterise and describe perivascular
      changes of the jugular vein like abscess, hematoma and periphlebitis. Well
      circumscribed masses with irregular, multiple, hypoechogenic areas, corresponding
      to fluids and necrotic tissues, suggested an abscess. A fresh hematoma, adjacent
      to the wall of the vein was shown as a clearly delineated structure with a
      hyperechogenic content. Cases with periphlebitis were characterised by a diffuse
      anechoic accumulation of fluids infiltrating the perivascular tissue. The
      diagnoses were proven by needle aspiration biopsy using ultrasound control.

PMID- 8578568
TI  - [Investigations on egg yolk-free diluting medium for the cryopreservation of bull
      spermatozoa].
AB  - On the basis of various laboratory researches and field experiments with 959
      alternating first inseminations the traditional tris-extender and a yolk-free
      medium for semen freezing on soy lecithin base were compared in studies using a
      split-sample technique. Concerning important criteria such as non-return-rate,
      conservation quality, and standard of hygiene and practicability, the alternative
      product was found at least of equal quality. The renunciation of chicken yolk is
      to be seen as a general advantage. Here, the development of cryomedia has been
      enriched by a useful and sensitive new component. Apart from being competitive
      this product is also the first to conform to future demands in standardization
      through ISO-norm.

PMID- 8578569
TI  - [Effect of housing of sows during parturition and the vitality of the piglets].
AB  - Group housing of sows had a positive effect on parturition, but led to a decrease
      in litter size by 1.2 alive born piglets per litter and a reduce in mean birth
      weight of piglets by 70 g; it had no effect on the vitality of piglets. A high
      birth weight, a long lasting placento-fetal blood transfer and an air temperature
      of more than 20 degrees C are factors with significant influence on vitality of
      neonates.

PMID- 8578570
TI  - [Skin diseases as a reason for condemnation of broiler carcasses].
AB  - The analysis of losses in slaughtered broilers based on the results of poultry
      meat inspection in a poultry slaughterhouse in 1991-1993 has shown that skin
      diseases are the main reason for condemnation of carcasses, followed by
      polyserositis and aerosacculitis, underdevelopment, skeletal diseases, and
      ascites syndrome. The incidence of skin diseases increased continuously between
      1991 and 1993. Amongst the skin diseases eight separate diagnoses were
      differentiated. Dermatitis with cellulitis, dermal carcinomatosis, skin tears,
      scabby hip, and breast blisters are the most frequent ones. However, the
      permanent increasing dermatitis with cellulitis as well as the frequency rank
      following dermal carcinomatosis are of utmost importance.

PMID- 8578571
TI  - [Control of ovulation in the mare with Ovuplant (short-term release of the GnRH
      analog deslorelin acetate). Overview of investigations from 1990 to 1994].
AB  - Ovuplant (deslorelin STI), when used in estrous mares with a follicle > or = 30
      mm, reliably causes acceleration of ovulation and assurance that > 80% of the
      treated mares will ovulate within 48 hours. Time to ovulation is reduced by 30
      hours or more. Treatment with Ovuplant had no adverse effects on pregnancy rates
      and did not increase the rate of early twin pregnancies. Treatment did not cause
      local or systemic side effects beyond short-term local irritation. Mares can be
      treated repeatedly without the development of tolerance or the loss of
      effectiveness. These studies have shown that Ovuplant can be used with a high
      level of assurance for success in the equine breeding industry. This will allow
      to reap benefits by reducing the number of breedings, saving stallion power and
      avoiding unnecessary inseminations. The mare has come an important step closer to
      a safe and effective management of ovulation.

PMID- 8578572
TI  - [Bilateral obstructive ecstasy of the kidneys in a newborn foal: a case study].
AB  - A report is given of obstructive ectasy of both kidneys in a newborn foal.
      Diagnosis and therapy are described as well as differential diagnosis.

PMID- 8578573
TI  - [Treatment of orbital abscesses and phlegmon in dogs and cats].
AB  - A diagnosis of orbital cellulitis or abscess was made in 13 dogs and four cats
      over the past five years. A foreign body was found in three of these cases. In
      five cases pasteurella spp. was isolated. In 15 of these cases the abscess was
      drained surgically. One dog was permanently blind due to inadequate surgical
      drainage of the abscess. In the remaining cases healing was uneventful. The
      surgical and medical therapy of orbital abscesses is illustrated by an exemplary
      case.

PMID- 8578574
TI  - [Urinary incontinence in castrated female dogs. 2. Therapy].
AB  - Several methods can be used for the treatment of urinary incontinence due to
      urethral sphincter incompetence in spayed bitches. The most commonly applied
      medicaments are either alpha-sympathomimetics or estrogens. Because of their high
      effectiveness and little side effects alpha-sympathomimetics should be preferred.
      A clinical field trial showed that ephedrine and phenylpropanolamine are highly
      efficient (ephedrine 93%, phenylpropanolamine 97%) and had very little side
      effects. It has proved to be valuable to apply 1.2-1.7 mg/kg/day (ephedrine)
      respectively 1.5 mg/kg twice a day (phenylpropanolamine) as an initial dosage and
      to reduce this step by step to the lowest dosage that keeps the dog continent.
      When urinary incontinence does not respond to conservative treatment several
      surgical techniques can be performed.

PMID- 8578575
TI  - [Unilateral duplication of the uveal tract in a cat. Coexistence of an excess
      failure of formation with ocular leukosis].
AB  - A six year old domestic cat, blind in the right eye from birth, slowly lost sight
      in the left eye. An ophthalmological examination of the right eye revealed uveal
      leucosis and unilateral duplication of the uveal tract. The additional tissues
      were rotated through 90 degrees resulting in displacement of the lens. In the
      left eye evidence of a previous retinal detachment and consecutive traumatic
      cataract were noted. The etiology of these pathological findings is discussed.

PMID- 8578576
TI  - [Secondary open angle glaucoma from osseous choristoma of the ciliary body in
      guinea pigs].
AB  - From 1983 to 1994 enucleated as well as bulbi obtained post mortem from 20 guinea
      pigs were ophthalmopathologically examined routinely. Eleven cases (one
      bilateral) with anamneses as hydrophthalmus, exophthalmus or retrobulbar abscess
      showed histologically osseous choristomas in the stroma of the ciliary body. In
      one case the osseous choristoma was already macroscopically recognizable. These
      heterotopic bone formations were causative for a secondary open angle glaucoma.
      Furthermore, it explains the obscured clinical symptoms of glaucoma together with
      the resulting exposition keratopathy. The aetiopathogenesis is discussed
      comparatively.

PMID- 8578577
TI  - [Rapid enzymatic test for diagnosis of parvovirus infections in dogs].
AB  - In this study 52 canine fecal samples were examined for the presence of canine
      parvovirus (CPV). The two different test systems used to confirm infection were
      electron microscopy as standard method and an enzyme-linked immunosorbent assay
      (ELISA). In comparison, the results conferred in 92.3%. The CPV ELISA had a
      sensitivity of 89.7% and a specificity of 100%. Therefore, it can be used as a
      quick, reliable method for diagnosis of canine parvovirus infection in veterinary
      practice.

PMID- 8578578
TI  - Induction of 73-kDa and 90-kDa heat shock protein expression in HL60 cells during
      differentiation.
AB  - We investigated the expression of heat shock proteins HSP73 and HSP90 in human
      promyelocytic line HL60 during their differentiation induced by phorbor ester and
      all trans retinoic acid (ATRA). Polyclonal antibodies which had been raised
      against HSPs purified from bovine brains were used to detect human HSPs.
      Semiquantitation of HSPs was performed by immunoblotting. Induction of monocytoid
      and granulocytoid differentiation with phorbor ester and ATRA was accompanied by
      increased expression of HSP73 and HSP90 with distinct kinetics. Increased
      expression of both HSPs was confirmed by immunocytochemical studies. Our results
      suggest that HSP73 and HSP90 may be involved in differentiation of HL60 cells.

PMID- 8578579
TI  - Hepatocellular carcinoma cases with five-year survival and prognostic factors
      affecting the survival time.
AB  - Between 1980 and 1994, 178 patients were confirmed to have hepatocellular
      carcinoma (HCC) in our hospital. The 5-year survival rates in patients with HCC
      of stage I, II and IVA were 38.1%, 31.8% and 3.9%, respectively. No patient in
      stage III or IVB survived for more than four years. The 5-year survival rates of
      the patients treated by hepatic resection, ultrasonically guided percutaneous
      ethanol injection and transcatheter hepatic arterial embolization were 53.7%,
      38.7% and 13.5%, respectively. The logrank test showed a significant difference
      in cumulative survival rates obtained in patients with HCC according to the tumor
      stage (p < 0.001) or principal treatment procedure (p < 0.001). Twelve patients
      survived for more than five years. We employed a Cox's proportional hazards model
      to estimate the factors significantly affecting the survival time. Variables with
      statistical significance were the clinical stage (p < 0.001), tumor size (maximal
      tumor diameter) (p < 0.001) and patient's age (p < 0.05). Conclusively, patients
      in the early stage of HCC associated with mild liver cirrhosis have a
      significantly better chance for long survival.

PMID- 8578580
TI  - Application of monoclonal antibodies to histologic diagnosis of gastric cancers.
AB  - Histologic diagnosis of poorly differentiated gastric adenocarcinomas by
      conventional hematoxylin-eosin (HE) staining is often limited by the quality of
      gastroendoscopic biopsy specimens. In this study we attempted to identify gastric
      cancer cells in biopsy specimens and ascites of gastric cancer patients using the
      gastric cancer reactive monoclonal antibodies S202 and S74. Twenty-four of 25
      specimens shown to contain cancer cells by HE staining were stained positively by
      monoclonal antibody S202. In contrast, 3 of 16 specimens that were diagnosed as
      not including cancer cells by HE staining was stained positively by S202. The
      possibility that cancer cells in the biopsy specimens were not detected by HE
      staining cannot be ruled out. Cancer cells in ascites of patients diagnosed with
      carcinomatous peritonitis by Papanicolaou staining were stained positively by
      monoclonal antibody S74. From these results, we conclude that monoclonal
      antibodies S202 and S74 may be useful supplemental agents for the diagnosis of
      gastric cancer.

PMID- 8578581
TI  - Do the effects of blood pressure control on the progression of diabetic
      nephropathy depend on disease stage?
AB  - To determine whether the control of blood pressure has a consistent effect on the
      progression of diabetic nephropathy with macroalbuminuria in diabetic patients
      with differing serum levels of creatinine, we evaluated the relationship between
      mean blood pressure and the yearly rate of increase in serum creatinine
      concentration in two groups: one with macroalbuminuria and a serum creatinine
      concentration less than 2 mg/100 ml (group 1), and the other with
      macroalbuminuria and a serum creatinine concentration of 2 mg/100 ml or more
      (group 2). Both groups showed a positive relationship between the mean blood
      pressure and the yearly rate of increase in serum creatinine concentration.
      However, when the yearly rate of increase in serum creatinine concentration was
      compared in patients from both groups with matched mean blood pressures of less
      than 100 mmHg, it was greater in patients of group 2 than in patients of group 1.
      Thus, although a beneficial effect of blood pressure control on the progression
      of diabetic nephropathy was found in both groups, the effect was less in patients
      with macroalbuminuria and a serum creatinine concentration of 2 mg/100 ml or more
      when mean blood pressure was controlled at less than 100 mmHg.

PMID- 8578582
TI  - Effects of dietary fiber on gastrointestinal transit time, fecal properties and
      fat absorption in rats.
AB  - The gastrointestinal transit time of food was determined by x-ray fluoroscopy
      using barium sulfate in rats fed with diets of various dietary fiber contents,
      and the effects of dietary fiber on the transit time, properties of feces, and
      fat absorption were examined. In 4- and 16-month-old rats fed with the diet for 3
      and 15 month, respectively, the transit time of the cecum and colon in those
      receiving 20 and 40% wheat bran diets was shortened compared with that in the 0%
      group. The fecal pellet number and volume increased as the wheat bran content of
      the diet increased. In another experiments, the daily total fat excretion was
      found to be the greatest in rats receiving 15% pectin diet, followed by rats
      receiving 15% cellulose and non-fiber diets, respectively. These results suggest
      that shortening of the transit time through the cecum and colon with increase of
      fecal volume and suppression of fat absorption all participate in the mechanism
      of the inhibitory action of wheat bran on carcinogenesis and on the development
      of diverticulum of the large intestine.

PMID- 8578583
TI  - Oxidative stress and antioxidant defenses in plasma of patients with Behcet's
      disease.
AB  - Plasma myeloperoxidase (MPO) and glutathione peroxidase (GSH-Px) activities, and
      malondialdehyde (MDA), ceruloplasmin (Cp), transferrin (TF), thiol (SH), selenium
      (Se) and copper (Cu) levels were determined in patients with Behcet's disease
      (BD), in order to investigate whether the plasma antioxidant defense system is
      impaired in BD. When compared to controls, plasma MDA, Cp, Cu levels and also
      plasma MPO activity were significantly higher in patients, whereas plasma TF, SH
      and Se levels, and also plasma GSH-Px activity were lower in BD patients than
      those in controls. In addition, there were significant and positive correlations
      between MDA-Cp, MDA-Cu, MDA-MPO, MPO-Cp, GSH-Px-Se, Cp-Cu, and TF-SH parameters,
      but negative correlations between MPO-TF and Cp-TF parameters in BD patients.
      Based on these findings, it is concluded that plasma antioxidant defense system
      is insufficient and impaired in BD.

PMID- 8578584
TI  - Contact dermatitis to biperiden and photocontact dermatitis to phenothiazines in
      a pharmacist.
AB  - A case of contact dermatitis to biperiden, an anti-Parkinson agent, and
      photocontact dermatitis to phenothiazines in a pharmacist was reported. The
      patient developed eczematous lesions on exposed area after she had worked at a
      psychiatric hospital for 6 months. She showed positive patch test reaction to
      biperiden. In addition, she reacted positively to photopatch testing with
      ultraviolet A and phenothiazines such as chlorpromazine and perphenazine. To our
      knowledge, contact dermatitis to biperiden has not been previously reported in
      the English literature.

PMID- 8578585
TI  - A target for phosphoinositide 3-kinase: Akt/PKB.

PMID- 8578586
TI  - Evolution of energetic metabolism: the respiration-early hypothesis.
AB  - The main energy-transducing metabolic systems originated and diversified very
      early in the evolution of life. This makes it difficult to unravel the precise
      steps in the evolution of the proteins involved in these processes. Recent
      molecular data suggest that homologous proteins of aerobic respiratory chains can
      be found in Bacteria and Archaea, which points to a common ancestor that
      possessed these proteins. Other molecular data predict that this ancestor was
      unlikely to perform oxygenic photosynthesis. This evidence, that aerobic
      respiration has a single origin and may have evolved before oxygen was released
      to the atmosphere by photosynthetic organisms, is contrary to the textbook
      viewpoint.

PMID- 8578587
TI  - Understanding, improving and using green fluorescent proteins.
AB  - Green fluorescent proteins (GFPs) are presently attracting tremendous interest as
      the first general method to create strong visible fluorescence by purely
      molecular biological means. So far, they have been used as reporters of gene
      expression, tracers of cell lineage, and as fusion tags to monitor protein
      localization within living cells. However, the GFP originally cloned from the
      jellyfish Aequorea victoria has several nonoptimal properties including low
      brightness, a significant delay between protein synthesis and fluorescence
      development, and complex photoisomerization. Fortunately, the protein can be re
      engineered by mutagenesis to ameliorate these deficiencies and shift the
      excitation and emission wavelengths, creating different colors and new
      applications.

PMID- 8578588
TI  - Defective protein folding as a basis of human disease.
AB  - The ability of a polypeptide to fold into a unique, functional, three-dimensional
      structure in vivo is dependent upon its amino acid sequence and the function of
      molecular chaperone proteins and enzymes that catalyse folding. Intense study of
      the physical chemistry and cell biology of folding have greatly aided our
      understanding of the mechanisms normally employed. Evidence is accumulating that
      many disease-causing mutations and modifications exert their effects by altering
      protein folding. Here we discuss the pathobiology of these processes.

PMID- 8578589
TI  - Molecular recognition between membrane-spanning polypeptides.
AB  - Integral membrane proteins have recently been shown to recognize and interact
      with other proteins within the membrane, either mimicking or altering their
      function, and with the lipid bilayer itself, resulting in a reorganization of
      native membrane protein. Membrane proteins are difficult to study using
      conventional methods such as X-ray crystallography, and so both synthesized and
      naturally occurring segments of membrane proteins have been used in the
      assessment of the mechanisms involved in their structure and organization.

PMID- 8578590
TI  - AU-rich elements: characterization and importance in mRNA degradation.
AB  - Adenylate/uridylate-rich elements (AREs) are found in the 3' untranslated region
      (UTR) of many messenger RNAs (mRNAs) that code for proto-oncogenes, nuclear
      transcription factors and cytokines. They represent the most common determinant
      of RNA stability in mammalian cells. Moreover, ARE-directed mRNA degradation is
      influenced by many exogenous factors, including phorbol esters, calcium
      ionophores, cytokines and transcription inhibitors. These observations suggest
      that AREs play a critical role in the regulation of gene expression during cell
      growth and differentiation, and in the immune response.

PMID- 8578591
TI  - Recognition and specificity in protein tyrosine kinase-mediated signalling.
AB  - There are several factors that contribute to the specificities of protein
      tyrosine kinases (PTKs) in signal transduction pathways. While protein-protein
      interaction domains, such as the Src homology (SH2 and SH3) domains, regulate the
      cellular localization of PTKs and their substrates, the specificities of PTKs are
      ultimately determined by their catalytic domains. The use of peptide libraries
      has revealed the substrate specificities of SH2 domains and PTK catalytic
      domains, and has suggested cross-talk between these domains.

PMID- 8578592
TI  - Methods and reagents. Quantitative PCR: an accurate measure of mRNA?
AB  - Methods and reagents is a unique monthly column that highlights current
      discussions in the newsgroup bionet.molbio.methds-reagnts, available on the
      Internet. This month's column discusses quantitative measurements of messenger
      RNA levels by using reverse transcription polymerase chain reaction (RT-PCR). For
      details on how to partake in the newsgroup, see the accompanying box.

PMID- 8578593
TI  - Dali: a network tool for protein structure comparison.

PMID- 8578594
TI  - T. H. Huxley and the 'protoplasmic theory of life': 100 years later.

PMID- 8578595
TI  - Hepatocyte growth factor/scatter factor (HGF/SF) in early development: evidence
      for a role in neural induction.

PMID- 8578596
TI  - Heart disease: daddies and timebombs.

PMID- 8578597
TI  - Bacterial genomes: a TIGR in the tank.

PMID- 8578598
TI  - Classification of LIM proteins.

PMID- 8578599
TI  - Return to sobriety after the catalytic party.

PMID- 8578600
TI  - Fos and bone cell development: lessons from a nuclear oncogene.
AB  - Vertebrate embryologists are beginning to understand the early developmental
      decisions that control the origin and patterning of skeletal elements. However,
      the regulators governing the development of the cells that form the skeleton,
      namely, bone and cartilage cells, are poorly understood. Recent studies using
      transgenic and knockout mice have established a unique role for the proto
      oncogene and nuclear transcription factor, Fos, in regulating the differentiation
      and activity of specific bone cell populations, both during normal development
      and in bone disease.

PMID- 8578601
TI  - Insight into the microphthalmia gene.
AB  - The murine microphthalmia gene (mi) is one of the last multi-allelic, classic
      coat-colour genes to be cloned in the mouse and, similar to many of these genes,
      encodes an exciting molecule that is is involved in multiple developmental
      processes. The existence of the numerous alleles has allowed the molecular
      dissection of the function of the MI bHLH-Zip transcription factor in vivo and
      offers a unique opportunity to understand the function of a multimeric
      transcription factor throughout development and in many tissues. It is also the
      gene mutated in some patients with the human deafness syndrome, Waardenburg's
      syndrome type II, and hence helps to understand this syndrome.

PMID- 8578602
TI  - Fathers and sons: the Y chromosome and human evolution.
AB  - It should be possible to use Y chromosome DNA polymorphisms to trace paternal
      lineages for evolutionary and other studies, but progress in these areas has been
      slow because it has been difficult to find suitable markers. However, it is now
      possible to use selected, slowly evolving polymorphisms to draw a rudimentary Y
      chromosome tree, while more rapidly evolving polymorphisms allow most independent
      Y chromosomes to be distinguished. Different populations often have
      characteristically different Y chromosomes, and Y chromosome studies are soon
      likely to make a major contribution to our understanding of the origins of modern
      humans.

PMID- 8578603
TI  - FlyBase: a virtual Drosophila cornucopia.

PMID- 8578604
TI  - The 'septide-sensitive' tachykinin receptor: still an enigma.

PMID- 8578605
TI  - NMDA receptor redox sites: are they targets for selective neuronal protection?
AB  - NMDA receptors play a central role in neuronal plasticity and in several
      pathological situations. Transient activation of this receptor triggers long-term
      potentiation, whereas sustained activation leads to cell death. Evidence for
      control of this activity by a redox site in cell cultures, brain tissues and in
      recombinant NMDA receptors are discussed by Henri Gozlan and Yehezkel Ben-Ari.
      The characteristics of this modulation and the consequences of redox state
      modifications on NMDA-mediated events are examined in vitro under physiological
      and pathological conditions. Since metabolic disorders enhance NMDA receptor
      function, the redox site could constitute a new target for selectively preventing
      in vivo the deleterious consequences of overactivation without blocking neuronal
      plasticity mediated by NMDA receptors.

PMID- 8578606
TI  - An evolutionary view of drug-receptor interaction: the bioamine receptor family.
AB  - The large molecular diversity of receptors and their subtypes means that the
      pharmacologist is faced with many puzzling characterization questions. First, the
      molecular diversity of the receptors is deciphered only in part by a
      pharmacological approach, which precludes a satisfactory receptor classification
      based solely on pharmacological characteristics. Second, the physiological
      counterpart of the numerous subtypes of receptors specifically activated by
      single endogenous ligands remains unclear. Here, Philippe Vernier and colleagues
      use the example of the bioamine G protein-coupled receptors to show that many of
      the apparent inconsistencies that emerge from pharmacological and molecular
      characterizations of receptors can be better understood if the evolutionary
      history of the receptors is taken into account.

PMID- 8578607
TI  - Small bone-building fragments of parathyroid hormone: new therapeutic agents for
      osteoporosis.
AB  - The brittle, fracture-prone bones of an osteoporotic postmenopausal woman are the
      products of an excessive uncompensated resorption of trabecular bone by
      osteoclasts. Osteoporosis is currently treated with the osteoclast suppressors
      calcitonin, bisphosphonates, or oestrogen, which stop further bone resorption
      without stimulating new bone growth. Here, James Whitfield and Paul Morley review
      the growing evidence that small adenylate cyclase-stimulating fragments of the
      parathyroid hormone are promising therapeutic agents for osteoporosis that
      potently stimulate osteoblasts to make mechanically strong or supranormally
      strong bone.

PMID- 8578608
TI  - Cyclic ADP-ribose, the ryanodine receptor and Ca2+ release.
AB  - In a variety of vertebrate and invertebrate tissues the ryanodine-sensitive Ca2+
      channel is the pathway for Ca2+ release from intracellular stores. The mechanism
      for activation of the ryanodine receptor-channel complex appears to depend both
      on the ryanodine receptor isoform and the cell type. In addition, a complex
      combination of endogenous intracellular compounds regulates channel gating. In
      this article, Rebecca Sitsapesan, Stephen McGarry and Alan Williams review the
      mechanisms involved in cyclic ADP-ribose (cADPR)-induced Ca2+ release and discuss
      the likelihood that cADPR-activated Ca2+ release is mediated by one of the
      recognized isoforms of the ryanodine receptor-Ca2+ channel complex.

PMID- 8578609
TI  - Central 5-HT4 receptors.
AB  - Activation of the 5-HT4 receptor mediates widespread effects in central and
      peripheral nervous systems. Recent developments, such as the identification of
      novel, selective agonists and antagonists, as well the cloning of the receptor,
      have provided insights into the physiological role of the receptor. In this
      article, Richard Eglen and colleagues assess the emerging evidence relating to
      the function of the 5-HT4 receptor in the brain. The cerebral distribution of the
      receptor, along with neurochemical and electrophysiological data, suggests a role
      in cognition. The role of the receptor in modulation of dopamine transmission and
      anxiolysis is also addressed.

PMID- 8578610
TI  - Pharmacological inhibition of restenosis: learning from experience.

PMID- 8578611
TI  - Detection of receptor subtypes in radioligand binding studies.

PMID- 8578612
TI  - Functional relevance of dopamine receptors.

PMID- 8578613
TI  - The European Medicines Evaluation Agency: role of experts in drug assessment.

PMID- 8578614
TI  - Nonlinear regression using spreadsheets.
AB  - Pharmacologists are often required to analyse nonlinear experimental effects by
      fitting the data to defined theoretical models. This may require a specialized
      computer program capable of performing nonlinear regression analysis, which can
      prove costly given the variety of pharmacological research. Here, Wayne Bowen and
      Jeff Jerman describe a generic method of performing nonlinear regression using
      spreadsheet applications, and demonstrate how this approach can be used to create
      automated systems of data analysis.

PMID- 8578615
TI  - Mechanisms and pharmacological manipulation of eosinophil accumulation in vivo.
AB  - The presence of eosinophils and their products in tissues is frequently
      associated with the pathogenesis of allergic inflammation. A better understanding
      of how these cells are recruited from the microcirculation will help in the
      development of therapies targeted at allergic disorders. Here, Mauro Teixeira,
      Timothy Williams and Paul Hellewell describe the current concepts of eosinophil
      accumulation, examine the potential ways of modulating this process, and discuss
      whether antagonists of eosinophil-specific mediators or functional antagonists
      would be the preferred therapies.

PMID- 8578616
TI  - Pharmacology of receptors for calcitonin gene-related peptide and amylin.
AB  - Calcitonin gene-related peptide (CGRP), a widespread neuropeptide with multiple
      actions, has substantial homology with amylin, a peptide implicated in insulin
      resistant diabetes, and adrenomedullin, a recently discovered potent vasodilator.
      There is controversy over the existence of CGRP receptor subtypes, and whether
      independent receptors exist for amylin and adrenomedullin. In this article, the
      current status of CGRP receptor classification is reviewed by David Poyner,
      taking particular account of species differences, and evidence is presented
      supporting the existence of multiple receptors for CGRP, as well as independent
      binding sites for amylin.

PMID- 8578617
TI  - [Response to the comment by F. Baumgart, R. Mathys Jr., on the contribution by H.
      Zitter, J. Poigenfurst: Evaluation of the mechanical properties of surgical
      screws after a torsion experiment].

PMID- 8578618
TI  - [Functional limitation of the forearm after shaft fracture in childhood. Possible
      role of the antebrachial interosseous membrane: MRI and ultrasound studies].
AB  - Based on follow-up examinations of 16 patients aged 5 to 15 years, the integrity
      of the interosseous membrane following forearm shaft fracture was evaluated. The
      examinations which included magnetic resonance imaging (MRI) and ultrasound
      scanning of both the fractured and the nonfractured forearms were conducted 4 to
      81 months after fracture. Using a 1.5 T MR tomograph, we obtained 20 cross
      sectional images arranged over the entire length of the forearm which was in
      neutral position, while sonographicly at 7.5 MHz we obtained cross-sectional
      views of the proximal, middle and distal forearm thirds with the forearm in
      pronation, neutral position and supination at a time. The MR image of the
      interosseous membrane is a thin hypointense line, occasionally showing low
      contrast irregularities on the fractured side such as thickenings, tears or
      curvature inconstancies which would suggest membrane alterations. However, these
      alterations appear to be less than expected. They are not clearly seen in the
      ultrasound views, where the interosseous membrane is found as an echorich line.
      According to our preliminary results, there seems to be a correlation between MR
      detected interosseous membrane alterations and initial fracture dislocation as
      well as functional fracture outcome, particularly forearm rotation.

PMID- 8578620
TI  - [Primary total endoprosthetic hip joint replacement in acetabulum fractures].
AB  - Conservative treatment of acetabular fractures mean a long period with
      immobilisation followed by quite a few of complications that are life-threatening
      to old patients. Besides that these fractures often cause painful posttraumatic
      osteoarthritis of the hip joint. Open reduction and osteosynthesis is favored
      more and more, but the complications described cannot be avoided absolutely by
      surgical treatment. The sequelae are risky reoperations and the necessity for
      implantation of total joint prosthesis. As shown in the enclosed case reports,
      total hip replacement can be emphasized as first step and as definitive surgery.
      Implantation of an artificial joint allows postoperative remobilisation with full
      weight bearing and long lasting immobilisation can be avoided. Therefore this
      kind of therapy is justified for treatment of old and polymorbid patients as an
      out of rule therapy.

PMID- 8578619
TI  - [Diagnosis and therapy of cruciate ligament injuries in childhood. Clinical
      results].
AB  - In 19 years 21 children were operated upon anterior or posterior ligament
      ruptures. Follow-up based on policlinical data and 12 out of 21 patients were
      tested on follow-up (average follow-up time: 5.5 years). We made notes of the
      clinical data of an examination with the knee-arthrometer KT-1000 as well as of
      radiologic and sonographic methods. The subsequent scoring revealed mostly good
      to very good results. Still, in the long run it would be desirable to perform a
      prospective multicenter study to obtain statistically relevant data to give
      advice for ideal surgical treatment of ligamentous knee injuries in children.

PMID- 8578621
TI  - [An unusual case of gunshot wound to the head].
AB  - We are going to present a special case of head injury caused by a gunshot. In
      this case it resulted in a fracture of the skull, but the bullet did not
      penetrate the skull. It was deflected by the bone, leaving the body at an angle.
      But bone fragments, acting as secondary bullets, penetrated the brain. In spite
      of a massive cerebral trauma and brain injury, no retrograde amnesia could be
      diagnosed. The patient recovered to such an extent, that he could return to his
      former job. Special characteristics of head injuries caused by bullets will be
      referred to.

PMID- 8578622
TI  - [Development of accident surgery at German universities].

PMID- 8578623
TI  - General management considerations for the trauma patient.
AB  - Proper evaluation, nursing care, physical therapy, and attention to the patient's
      general comfort are essential to the successful management of animals with severe
      trauma. Evaluation is important because failure to identify all injuries early in
      the management of a trauma patient may have unfavorable effects on the eventual
      outcome of the case. Once therapy is underway, ensuring the patient's comfort,
      maintaining fluid and electrolyte balance, and providing a well-planned
      rehabilitation program are essential to speed an enhance the recovery of these
      patients.

PMID- 8578624
TI  - Management of fracture-associated thoracic trauma.
AB  - Animals with thoracic injury that survive long enough to receive veterinary
      attention are often through the most critical post-traumatic period. A small
      proportion will require prompt, aggressive treatment of life-threatening
      injuries. Many have self-limiting thoracic injuries that can endanger the animal
      if overlooked when general anaesthesia is attempted for surgical repair of more
      obvious injuries. Other lesions can be exacerbated by inappropriate therapy.
      Through evaluation is needed for recognition and proper management of thoracic
      injuries that pose both immediate and delayed threat to life.

PMID- 8578625
TI  - Client counseling in orthopedic emergencies.
AB  - Important client communication issues associated with most orthopedic emergencies
      are addressed. Information on client communication and support, providing a
      prognosis, discussing economic concerns, discharge planning, euthanasia, and
      client grief is presented. The issue of animal abuse as a cause of orthopedic
      emergencies also is examined.

PMID- 8578626
TI  - Fracture management decisions.
AB  - Management decisions regarding the care of fracture patients are best performed
      by a veterinary surgeon who, in logical manner, takes into account the
      configuration and characteristics of the individual fracture, considers patient
      attributes such as temperament, evaluates all the possible fixation attempts for
      success, and then selects the most likely fracture fixation device and uses it
      along well-established guidelines. Fracture repairs should achieve anatomic
      reduction, rigid stability, and early return to function to provide for good
      success. Fracture repairs that are beyond the experience, expertise, or equipment
      of a general practitioner should be referred to a qualified surgeon. Most
      complications of fracture repair can be traced to case management or technical
      errors.

PMID- 8578627
TI  - Anesthetic management of the trauma patient.
AB  - The key to safe anesthesia of a trauma patient is preoperative stabilization. It
      minimizes the anesthesia risk and allows proper choices of anesthetic drugs.
      Adequate monitoring throughout anesthesia allows rapid and adequate therapeutic
      intervention. Proper control of upper airway and support of physiologic functions
      will enhance the chances of the patient to survive anesthesia.

PMID- 8578628
TI  - Open fracture management.
AB  - Open fractures are complicated cases requiring methodical evaluation for the
      optimal outcome. The initial handling of the case can play a major role in the
      outcome of the fracture. Management of the pet with an open fracture from the
      time or presentation through the postoperative period has been presented.
      Prognosis and some complications associated with open fractures were outlined and
      treatment options for some of the complications were provided.

PMID- 8578629
TI  - Gunshot injuries: pathophysiology and treatments.
AB  - The increase in gun ownership and shootings of dogs and cats in urban and rural
      areas has made it important for veterinarians to be familiar with the treatment
      of gunshot injuries. The damage inflicted on the soft tissues and bone depends on
      the type of firearm used and the range at which it was fired. Proper initial
      evaluation and management are critical in the treatment of these injuries.
      Fractures caused by gunshots are contaminated and can often be stabilized with
      external fixation. Complications and special considerations of these fractures
      and associated soft tissue injuries are discussed.

PMID- 8578630
TI  - Skull trauma and mandibular fractures.
AB  - This article discusses the treatment of skull and mandibular fractures in small
      animals as well as fixation techniques, including interdental fixation, external
      skeletal fixation, intraoral splints, wiring, and pinning. Information is
      provided on the treatment of loose and damaged teeth in the fractured area.
      Management of temporomandibular joint luxation also is addressed.

PMID- 8578631
TI  - Spinal fracture/luxation.
AB  - Clinical management of the spinal fracture/luxation patient requires prompt and
      accurate diagnosis of the extent of injury coupled with intensive medical or
      surgical intervention. Convalescent patient care is often physically challenging
      and labor intensive.

PMID- 8578632
TI  - Traumatic joint luxations in small animals.
AB  - Proper management of traumatic joint luxations in small animals requires complete
      assessment and treatment of life-threatening injuries, early joint reduction,
      stabilization of the joint, and early return to joint function. The methods of
      reduction vary with the joint involved but can often be achieved in a closed
      fashion. Joint stability is maintained by external coaptation or internal
      stabilization methods, depending on the degree of laxity present after reduction.
      Once joint stability is achieved, passive and active physical therapy is
      important to establish normal joint function. Reluxation, lameness, and
      degenerative joint disease are possible sequelae of traumatic joint luxations.

PMID- 8578633
TI  - Management of penetrating joint injuries.
AB  - A classification scheme for penetrating joint injuries is presented. Diagnostic
      techniques and treatment recommendations for managing penetrating joint injuries
      in small animals are described. Techniques used in human and equine patients are
      discussed for comparison.

PMID- 8578634
TI  - Glomerular ultrastructural lesions of idiopathic cutaneous and renal glomerular
      vasculopathy of greyhounds.
AB  - Idiopathic cutaneous and renal glomerular vasculopathy (CRGV) (Alabama rot) is a
      potentially fatal disease of unknown etiology that affects the skin and kidneys
      of racing- and training-age Greyhounds. Ultrastructural examinations were
      performed on two healthy control Greyhounds and 12 Greyhounds diagnosed with CRGV
      based on the presence of characteristic, well-demarcated cutaneous ulcers of the
      extremities (12/12), thrombocytopenia (< 200,000 platelets/dl) (12/12), and acute
      renal insufficiency (BUN > 40 mg/dl, serum creatinine > 2.0 mg/dl) (7/12). Early
      glomerular ultrastructural changes included endothelial swelling, detachment, and
      necrosis; membranous whorl formation; and platelet adhesion and aggregation. Some
      capillaries were occluded with aggregated platelets, cellular fragments, and
      fibrin. Later changes included narrowing of capillary lumina and thickening of
      glomerular capillary walls by subendothelial accumulation of flocculent,
      amorphous, variable electron-dense material and occasionally erythrocytes,
      cellular processes, and fibrin. Glomerular endothelial cells were increased in
      number and plump, with villouslike cytoplasmic projections. Mesangial cell
      cytoplasmic processes occasionally were interposed between the endothelium and
      the basement membrane. No etiologic agents or electron-dense deposits typical of
      immune complexes were observed. Although the specific etiology was not
      determined, the ultrastructural changes suggest that glomerular endothelial
      damage is an important early event in the pathogenesis of CRGV.

PMID- 8578635
TI  - Glycogen storage disease type Ia in two littermate Maltese puppies.
AB  - Glycogen storage disease type Ia (GSD-Ia) (von Gierke's disease) was identified
      in two 47-day-old littermate Maltese puppies. The puppies were presented for
      necropsy with a history of failure to thrive, mental depression, and poor body
      condition. Gross findings included small body size and emaciation (212 and 246 g
      versus 595 g for normal littermate), severely enlarged pale livers (48 and 61 g),
      and pale kidneys. Histologically, there was marked diffuse vacuolation of
      hepatocytes with large amounts of glycogen and small amounts of lipid. Renal
      tubular epithelium was mildly to moderately vacuolated. Soft tissue
      mineralization was present in renal tubules and pulmonary alveolar septa.
      Biochemical analysis showed that levels of glucose-6-phosphatase were markedly
      reduced in liver (0.3 and 0.4 microM/minute/g tissue versus 4.7 +/- 1.5
      microM/minute/g tissue for controls) and kidney (0.45 and 0.4 microM/minute/g
      tissue versus 4.1 microM/minute/g tissue for controls) and that glycogen content
      was increased in liver (9.4% and 9.4% versus 1.3% +/- 1.4% for controls). This is
      the first confirmed report of animals with glycogen storage disease type Ia.

PMID- 8578636
TI  - A sequential study of the light and electron microscopic liver lesions of
      infectious anemia in Atlantic salmon (Salmo salar L.).
AB  - The present study describes light and electron microscopic changes in the liver
      of Atlantic salmon during the development of infectious salmon anemia (ISA).
      Atlantic salmon postsmolts weighing 80-100 g were infected by intraperitoneal
      injections, and liver samples were collected sequentially between day 0 and day
      25 post infection (p.i.), with time intervals of 3-4 days. At each collection
      time, livers from five infected fish and two control fish were examined. Changes
      involving the perisinusoidal macrophages were observed by transmission electron
      microscopy, from day 4 p.i. Large vacuoles, containing a fine-granular material
      with low electron density, accumulated in the cytoplasm. These changes persisted
      and became more severe throughout the investigation, leading to a considerable
      increase in the size of the cells. At day 14 p.i., degenerative features of the
      sinusoidal endothelium were observed. By day 18 p.i., areas of the liver were
      devoid of a sinusoidal endothelial lining, bringing hepatocytes in direct contact
      with blood cells. At this stage, the sinusoids were moderately congested. From
      day 21 p.i., heavy sinusoidal congestion, peliosis hepatis, and degeneration of
      the hepatocytes were observed. No virus was observed in any of the inhabitant
      cell types of the liver. Gross and light microscopic changes were first recorded
      at day 18 p.i., as was a significant decrease in the hematocrit values. By day 25
      p.i., characteristic multifocal, confluent, hemorrhagic necroses were present.
      Results of the present investigation suggest that the liver lesions observed with
      ISA are not the result of the development of an anemia alone or caused by direct
      viral damage to hepatocytes. Hepatocellular degeneration succeeded changes in the
      perisinusoidal macrophages and degeneration of the sinusoidal endothelium. These
      changes may have impeded the sinusoidal blood flow and hence caused an ischemic
      hepatocellular necrosis.

PMID- 8578637
TI  - Cutaneous melanocytomas in 10 young cattle.
AB  - Ten melanocytomas from 10 cattle were diagnosed by histopathologic examination of
      biopsy specimens submitted to the Veterinary Medical Diagnostic Laboratory,
      University of Missouri, between 1 January 1986 and 31 December 1993. One tumor
      was congenital; the others were first noticed between 2 months and 2 years of age
      (means = 9.9 months). Six tumors occurred in purebred (3) or crossbred (3) Angus
      cattle; one tumor each occurred in a Holstein, a Shorthorn, a Simmental, and a
      beef calf of unrecorded breed or coat color. Five calves were female, and five
      were male. Five tumors occurred in truncal dermis or subcutis (three in abdominal
      skin), four occurred on a limb, and one occurred on the jaw. Tumors varied in
      histologic appearance, but all were pigmented and all had few mitotic figures.
      Outcome was known for 8/10 cattle. In four cattle followed for at least 1 year,
      the tumor did not recur after surgical excision. Another heifer had residual gray
      tissue at the tumor site after surgery but remained in the herd without regrowth
      of the tumor 30 months after excision. Three other calves were slaughtered within
      6 months of excision without apparent recurrence of the tumor.

PMID- 8578638
TI  - Neuronal ceroid-lipofuscinosis in a cat.
AB  - Neuronal ceroid-lipofuscinosis was diagnosed in a young adult domestic short
      haired cat euthanatized because of severe progressive neurologic disease.
      Clinical signs included blindness, seizures, and decreased mentation. An
      autofluorescent pigment, identified as ceroid-lipofuscin by electron microscopy
      and staining properties, was found within neurons of the central and peripheral
      nervous systems. A diffuse reactive astrocytosis accompanied by multifocal
      microgliosis was visible in all areas of the brain. Retinal atrophy with
      intraneuronal lipopigment accumulation was also identified. Contrary to the human
      neuronal ceroid-lipofuscinoses, pigment deposition appeared to be restricted to
      neural tissues.

PMID- 8578639
TI  - An animal model of gastric ulcer due to bacterial gastritis in mice.
AB  - Conventional female BalbC mice were inoculated with Gastrospirillum-like bacteria
      in mouse gastric homogenate or in 5.0-microns filtrate of gastric homogenate. The
      bacteria were originally isolated from cheetahs with gastritis. The mice were
      killed 6 months, 7 months, or 1 year after inoculation. All mice became infected
      with Gastrospirillum-like bacteria that were confined to the gastric mucosa.
      Control mice, given either sterile Brucella broth, 0.22-microns filtrate of
      infected gastric homogenate, or uninfected gastric homogenate did not become
      infected with bacteria. Lesions in infected mice included severe
      lymphoplasmacytic gastritis (26/26 infected mice), gastric epithelial hyperplasia
      (25/26 infected mice), and gastric ulceration (11/26 infected mice). Neutrophilic
      inflammatory cell infiltrates were inconsistent. None of the uninfected control
      mice had Gastrospirillum-like bacteria, gastritis, gastric epithelial
      hyperplasia, or gastric ulceration. These results implicate Gastrospirillum-like
      bacteria from cheetahs in the pathogenesis of gastric ulceration. This model will
      be useful in investigating the mechanisms of gastric ulceration associated with
      bacterial gastritis.

PMID- 8578640
TI  - Eosinophil and foam cell accumulation in lungs of Sprague-Dawley rats fed
      purified, biotin-deficient diets.
AB  - One hundred twenty male Sprague-Dawley rats (3 weeks old) were given biotin
      deficient diets containing ovalbumin as the protein source. Ten control rats of
      the same origin were fed a commercially available purified diet that used casein
      as a protein source. Eosinophils and histiocytes were observed at a higher
      frequency in lungs of rats fed the purified diets containing ovalbumin than in
      the controls. Foam cells were confined to subpleural and peribronchial regions,
      reacting positively to anti-lysozyme antibody. The incidence of pulmonary
      histiocytosis was 76/120 rats (63.3%) in the groups fed the ovalbumin-containing
      diets as compared with 1/10 (10.0%) in the controls. The accumulation of
      eosinophils in lung was highest (6/24 rats, 25%) at 3 months. This lesion was not
      seen in the controls. Eosinophils were first observed in the perivascular and
      peribronchiolar regions. In advanced lesions, macrophages and mast cells also
      appeared in the lesions, which at this stage resembled so-called idiopathic
      chronic eosinophilic pneumonia of human beings. Neither foam cells nor
      eosinophils were present in any of the other organs. Because there was no
      difference in the composition of the diets with the exception of the protein
      source, these lung lesions may be due to biotin deficiency resulting from the use
      of ovalbumin as the protein source.

PMID- 8578641
TI  - Scarcity of gamma delta T cells in intestinal epithelia containing coccidia
      despite general increase of epithelial lymphocytes.
AB  - Lymphocytes of intestinal epithelia were examined in lambs experimentally
      infected with coccidia. Fourteen conventional, coccidia-free 3-week-old lambs of
      the Dala breed were given either 250,000 (eight lambs in experiment 1) or 100,000
      (six lambs in experiment 2) sporulated oocysts of Eimeria ovinoidalis (> 99.9%
      pure) via a stomach tube. Nine lambs (five in experiment 1 and four in experiment
      2) of the same age served as uninoculated controls. The infected lambs developed
      diarrhea and dehydration between days 10 and 13 after infection. Intestinal
      specimens were collected 10-20 days after inoculation. A heavy multifocal
      infection of the epithelium comprising schizonts, gamonts, and oocysts resulted,
      with changes being most pronounced in the large intestine and the terminal part
      of ileum. Lesions included villous atrophy, villous fusions, and crypt
      hyperplasia. Computer-assisted morphometric analysis was applied to
      immunoperoxidase-stained sections for quantification of intraepithelial T cell
      subsets and included the distal jejunum of lambs of experiment 1. A significant
      increase in the epithelial area of the distal jejunum occupied by CD8+
      lymphocytes was found in the infected lambs as compared with uninfected controls
      (18.3% versus 3.7%). The increased presence of CD8+ cells may be of significance
      in the intestinal immune response to ovine coccidiosis. A moderate, overall
      increase was also found for the gamma delta lymphocytes in the jejunal
      epithelium. Examination of the ileum of infected lambs of both experiments showed
      a scarcity of gamma delta cells (0.4% of epithelial area) in stretches of
      epithelium infected by coccida as compared with adjacent noninfected epithelium
      (4.0% of epithelial area).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8578642
TI  - Immunohistologic studies on subpopulations of lymphocytes in cattle with enzootic
      bovine leukosis.
AB  - The distribution of subpopulations of lymphocytes in lymph nodes and tumors from
      cattle with enzootic bovine leukosis (EBL) was examined by immunohistochemistry
      using a panel of monclonal antibodies against leukocyte differentiation molecules
      of EBL. The lesions in lymph nodes could be divided into three types based on the
      extent of infiltration and proliferation of neoplastic cells with provirus and
      differential expression of leukocyte differentiation molecules. The number of B
      B2+, sIgM+ cells was reduced in frequency in follicles during the neoplastic cell
      proliferation. CD4- and CD8-positive alpha/beta T cells and gamma/delta T cells
      positive for WC1 (workshop cluster designation) were also reduced in frequency in
      areas infiltrated with neoplastic cells. Almost all neoplastic cells were B-B2-
      and IgM-positive. However, there were a few B-B2- and/or IgM-negative cells or
      cells stained faintly in all cases. WC1+ cells were not observed in tumor
      tissues. However, CD4+ and CD8+ cells were observed throughout tumor tissues,
      suggesting a role for these cells in tumor immunity.

PMID- 8578643
TI  - Progressive retinal toxicity in neonatal rats treated with D,L-2-amino-3
      phosphonopropionate (D,L-AP3).
AB  - D,L-2-amino-3-phosphonopropionate (D,L-AP3) has complex pharmacologic activity at
      central nervous system metabotropic glutamate receptors important in excitatory
      neurotransmission and development. Previous studies have described retinal and
      optic nerve atrophy in adult rats after postnatal treatment with D,L-AP3. Using
      neonatal male Sprague-Dawley rats, the present studies examined normal postnatal
      retinal development (n = 20) and the progression of retinal toxicity induced by
      D,L-AP3 (n = 30). Retinal development was examined by light microscopy on
      postnatal days (PNDs) 5, 9, 12, 16, and 22. Between PNDs 5 and 16, the retina
      underwent considerable postnatal differentiation. A prominent neuroblastic layer
      evident on PND 5 differentiated into outer retinal layers by PND 16. To examine
      the effects of D,L-AP3, neonatal rats were treated intraperitoneally with sterile
      water or 400 mg/kg/day D,L-AP3 on PNDs 3-6. On PNDs 5, 7, 10, 15, and 20, retinas
      were examined by light and electron microscopy. On PNDs 5 and 7, cells with
      swollen, pale cytoplasm were evident in the more differentiated inner nuclear
      layer and in the middle of the developing neuroblastic layer. Retinal toxicity
      rapidly progressed after treatment, because developing outer retinal layers had
      cytoplasmic swelling, nuclear pyknosis, and necrosis on PND 10. By PNDs 15 and
      20, retinal dystrophy was severe and involved primarily outer layers. This study
      showed that early postnatal treatment with D,L-AP3 initiates rapidly progressing
      retinal toxicity, thus implicating metabotropic glutamate receptors in the
      postnatal retinal development of rats.

PMID- 8578644
TI  - Observations on neonatal mortality of the Chacoan peccary, Catagonus wagneri.
AB  - The considerable neonatal mortality of a captive population of Chacoan peccaries,
      the tagua (Catagonus wagneri), in Paraguay was investigated with the examination
      of six newborn animals and one adult. Most deaths occur primarily because of
      restriction of space resulting in competition for space and nutrition. The adult
      had nonlethal inhalation pulmonary anthracosis. Neonatal pulmonary nocardiosis
      was noted in one infant and is believed to be related to the dust storms
      prevailing locally. Another neonate had a duplication of the pelvis, rear
      extremities, and one ovary, representing a type of conjoined twin classified as
      ischiopagus.

PMID- 8578645
TI  - Malignant melanocytic neural crest tumor in a young chicken (Gallus domesticus).
AB  - A malignant melanocytic tumor was found in an 8-week-old chicken. The tumor,
      which was composed of melanocytes, ganglion cells, nerves, and primitive pressure
      receptors, was examined by light microscopy, transmission electron microscopy,
      and immunohistochemistry. Antibodies to neuron-specific enolase (NSE), glial
      fibrillary acidic protein (GFAP), and S-100 protein variably stained nerves, but
      melanocytes were only rarely immunolabelled by NSE antibodies and there was no
      specific staining of these cells for S-100 or GFAP. Ultrastructurally, neoplastic
      melanocytes contained melanin within melanosomes and premelanosomes and did not
      resemble Schwann cells.

PMID- 8578646
TI  - Wilson's disease-like lesion in a calf.
AB  - Wilson's disease-like lesion was seen in a 2-month-old calf. Fibrosis was
      apparent in the liver, but there was no cholestasis or icterus. Marked spongy
      degeneration was seen in the central nervous system. Hepatic and brain copper
      values were significantly higher than normal: 1970 and 113 ppm dry matter,
      respectively. Serum ceruloplasmin was lower than normal: 17.5 U/liter. Etiology
      of this disease was unknown, but there is no evidence that the calf ingested a
      large quantity of copper.

PMID- 8578647
TI  - Ocular Halicephalobus (syn. Micronema) deletrix in a horse.
AB  - Ocular contents from a horse with a 4-week history of severe unilateral uveitis
      were submitted for histopathologic examination. A severe unilateral granulomatous
      chorioretinitis with intralesional Halicephalobus deletrix was diagnosed. The
      horse developed progressive neurologic signs several days following the surgery
      to remove ocular contents and implant a prosthesis and was subsequently
      euthanatized. A severe multifocal granulomatous encephalitis with intralesional
      H. deletrix, localized primarily to the optic chiasm, thalamus, and brain stem,
      was diagnosed from tissues acquired at necropsy. The other eye was not affected.
      This is the first report of ocular parasitism by H. deletrix and suggests
      possible systemic dissemination from a primary site in the eye.

PMID- 8578648
TI  - An investigation into the health and welfare of red squirrels, Sciurus vulgaris,
      involved in reintroduction studies.
AB  - The threats posed by parapoxvirus infection, metabolic bone disease and
      coccidiosis to the reintroduction of red squirrels into Thetford Chase were
      investigated by making blood biochemical, radiological and parasitological
      examinations on the squirrels before they were released and on resident
      squirrels. Red squirrels found dead in Thetford Chase were examined post mortem
      by parasitological, electron microscopical and radiological techniques.
      Parapoxvirus infection was the probable cause of death of two red squirrels.
      Parapoxvirus infection may be a significant threat to remnant populations of red
      squirrels in England, and to the success of conservation measures.

PMID- 8578649
TI  - Continuous monitoring of ECG in horses at rest and during exercise.
AB  - A method for the continuous monitoring of the electrocardiogram (ECG) of horses
      at rest and during exercise was evaluated in five healthy horses. The horses
      spent 24 hours in a loose box and performed a standardised exercise test on a
      treadmill during this period. Two bipolar leads were recorded, lead 1 between the
      xiphoid and the left withers, and lead 2 between the left ventral thorax and the
      left dorsal thorax, using disposable electrodes. The quality of the ECGs enabled
      both an 'operator-controlled' and an automatic analysis to be made. Lead 1 was
      the most stable during exercise and lead 2 during rest in the loose box. The
      heart rate and occurrence of arrhythmias were assessed over 22 hours. During the
      boxed period the heart rate varied from 31 +/- 2 to 138 +/- 11 beats per minute
      (bpm) and during exercise it varied from 79 +/- 8 to 177 +/- 12 bpm. All the
      horses had sinus arrhythmias, sinus tachycardias and second degree
      atrioventricular blocks. One horse developed a ventricular escape rhythm.

PMID- 8578650
TI  - Evaluation of an O-antigen ELISA for screening cattle herds for Salmonella
      typhimurium.
AB  - A total of 2585 serum samples from 62 dairy herds located in four different
      regions of Denmark were tested in an O-antigen (0:1,4,5,12)-based ELISA for the
      detection of antibodies against Salmonella typhimurium. Ten closed herds from an
      island with no reported occurrence of salmonellosis for several years, and 12
      herds from a salmonella enzootic area which had had clinical outbreaks of S
      typhimurium were used to define a herd ELISA cut-off value. When herds with at
      least 5 per cent of the serum samples having an optical density of > 0.5 were
      considered ELISA-positive, all 10 herds from the salmonellosis-free island were
      ELISA-negative, and all but one of the 12 S typhimurium-infected herds were ELISA
      positive, which resulted in a herd test sensitivity of 0.92 and herd test
      specificity of 1.0. Eleven of the 12 S typhimurium-infected herds were negative
      in a blocking ELISA based on a monoclonal antibody to the 0:9 antigen of the
      serogroup D salmonellas, indicating the possibility of rapid serogroup-specific
      screening of herds by means of these two tests. Ten other randomly selected herds
      with clinical outbreaks of S dublin were all, to a large extent, positive in the
      0:1,4,5,12-ELISA, whereas a S dublin (0:1,9,12)-ELISA described previously
      appeared to be more serogroup D-specific. Thus, the 0:1,4,5,12-ELISA appears to
      be useful for detecting herd infections with S typhimurium, and positive
      reactions may be further discriminated by the serogroup D-specific ELISA.

PMID- 8578651
TI  - Failure to demonstrate histological changes of digital or interdigital dermatitis
      in biopsies of slurry heel.

PMID- 8578652
TI  - Renal carcinoma in a chimpanzee (Pan troglodytes).

PMID- 8578653
TI  - Veterinary manpower and 24-hour service.

PMID- 8578654
TI  - Dental disease in rabbits.

PMID- 8578655
TI  - Gangrene and radiography.

PMID- 8578656
TI  - Veterinary manpower and 24-hour service.

PMID- 8578657
TI  - Time for 'a complete change of attitude' towards sheep scab.

PMID- 8578658
TI  - Farmers call for overhaul of badger control policy.

PMID- 8578659
TI  - How much are veterinary nurses worth?

PMID- 8578660
TI  - Gastro-oesophageal reflux during anaesthesia in the dog: the effect of
      preoperative fasting and premedication.
AB  - Lower oesophageal pH was monitored in 240 anaesthetised dogs. The incidence of
      gastro-oesophageal reflux was 16.3 per cent and most of the reflux episodes
      occurred shortly after the induction of anaesthesia. The refluxate was nearly
      always acid (pH < 4.0), but in 10.3 per cent of the cases it was alkaline (pH >
      7.5); gastric contents of pH below 2.5 were refluxed on 19 occasions (7.9 per
      cent). Regurgitation occurred in only one dog. Prolonging preoperative fasting
      was associated with an increased incidence of reflux and increased gastric
      acidity. Premedication with diazepam was associated with fewer reflux episodes
      than premedication with atropine and propionylpromazine.

PMID- 8578661
TI  - Pharmacokinetics and therapeutic potential for repeated oral doses of
      trimethoprim/sulphachlorpyridazine in horses.
AB  - The pharmacokinetic parameters of a powder formulation of
      trimethoprim/sulphachlorpyridazine were studied in eight healthy horses which
      received 5 mg/kg trimethoprim and 25 mg/kg sulphachlorpyridazine 12-hourly with
      concentrate for five days. The intake of the medicated concentrate by the horses
      was variable during the first two days, but after they became accustomed to the
      taste the intake by all the horses during the last three days was good. Faecal
      samples taken before and on the last day of the drug administrations were
      negative when cultured for salmonella. Compared with the results of a previous
      single-dose experiment, higher plasma concentrations and a higher area under the
      curve for both the drugs were observed. The repeated doses provided plasma
      concentrations above the minimal inhibitory concentration for Streptococcus
      zooepidemicus, S equi, Actinobacillus equuli and Rhodococcus equi isolated from
      the respiratory tract of horses. Synergism between the two drugs occurred at
      different drug concentration ratios with different bacterial species.

PMID- 8578662
TI  - A survey of urban pet ownership in Bali.
AB  - A personal interview survey was conducted to determine the type and
      characteristics of the animals kept by 200 households in a traditional Balinese
      community in Denpasar, Indonesia. Fifty-seven per cent of the households owned an
      animal. One or more birds were kept by 45.2 per cent of households, dogs were
      owned by 39 per cent, cats by 18.5 per cent and some other sort of animal was
      owned by 4.5 per cent of households. Chickens were the most commonly kept bird
      (29.5 per cent of households) followed by cuckoos (10.5 per cent) and doves (8.5
      per cent). More cats were kept in households with cats (average of 1.5) than dogs
      in the households with dogs (1.32. More male dogs and cats (85 per cent and 73
      per cent, respectively) were kept than females. Only 11 per cent of the female
      dogs were neutered compared with 44 per cent of males and no female cats were
      neutered compared with 9.5 per cent of males. This low level of neutering
      accounted for the finding that 69 and 78 per cent of the entire bitches and
      queens had had litters in the 12 months preceding the survey.

PMID- 8578663
TI  - Physiotherapy as an aid to treatment of bilateral femoral paralysis in a calf.

PMID- 8578664
TI  - Control of sheep scab (Psoroptes ovis) on artificially infested sheep with a
      single injection of doramectin.

PMID- 8578665
TI  - Suspected corpus cavernosum trauma in three dogs.

PMID- 8578666
TI  - Equine influenza in vaccinated horses.

PMID- 8578667
TI  - Potential risk of effects of antimicrobial residues on human gastrointestinal
      microflora.

PMID- 8578668
TI  - Use of moxidectin in goats in New Zealand.

PMID- 8578669
TI  - [Acute occlusion of the coronary artery after transluminal balloon coronary
      angioplasty].
AB  - Acute occlusion of the coronary artery is one of the most grave complications of
      transluminal balloon coronary angioplasty (TBCA). Singling out a group of
      patients at risk of developing this complication is important for the definition
      of indications for TBCA, for prediction of its results, and selection of
      treatment strategy. This research was aimed at elucidation of the relationship of
      the clinical and angiographic factors, on the one hand, and development of acute
      occlusion following TBCA, on the other. TBCA was carried out in 162 patients.
      Eight (4.9%) patients developed acute occlusion of the coronary artery, which was
      complicated by acute myocardial infarction in 50% cases. It was preceded by
      complicated stenosis before TBCA and manifest dissection of the vascular wall
      after the procedure. Occlusion of the coronary artery was effectively eliminated
      by intravenous and intracoronary thrombolysis, repeated emergency TBCA, and
      aortocoronary shunting.

PMID- 8578670
TI  - [Catheter therapy of congenital cardiovascular defects].
AB  - The authors analyze the experience gained in catheter operations performed at
      their Department over the recent 28 years. A total of 500 balloon (Rashkind) and
      35 knife (Park) atrioseptostomies were performed in critical patients with
      different "blue" congenital diseases over this period. An immediate hemodynamic
      effect at the operation table was attained in 95% of patients. Transluminal
      balloon valvuloplasty (TLBVP) was performed in 372 patients with valvular
      stenosis of the pulmonary artery. The results of this operation depend on the
      patient's age, anatomy of the defect, and correct choice of the diameter of
      balloon catheter. This intervention is particularly effective in patients aged
      under 1. In patients with combined valvular and infundibular stenosis the results
      of TLBVP depend on the severity of stenosis and age of patient. An attempt at
      TLBVP of congenital aortal stenosis was undertaken in 67 patients. Valvuloplasty
      was carried out in 57 patients. The operation was effective in 13 (62%) out of 21
      patients aged under 1. The mortality in this group was 5.5%. Balloon
      valvuloplasty of the pulmonary artery was carried out in 71 patients with
      cyanotic congenital heart diseases. The intervention helped eliminate the
      critical state, rise the systolic pressure in the pulmonary artery, improve blood
      saturation with oxygen, and evade the operation for creation of a systemic
      pulmonary anastomosis. Isolated and postoperative stenoses of pulmonary arteries
      were removed in 65 patients. Six Johnson and Johnson stents were effectively
      implanted to 3 patients with rigid postoperative stenoses; in 32 patients
      transluminal balloon angioplasty (TLBAP) for coarctation and recoarctation of the
      aorta brought about a satisfactory immediate hemodynamic effect. TLBAP of Blalock
      Taussig's stenosed anastomosis were performed in 60 patients with various
      cyanotic congenital heart diseases. Its results were good in 39 (65%) patients,
      satisfactory in 19 (31.7%), and unsatisfactory in only 2 (3%) cases. Of the novel
      endocardial interventions, dilatation of the conduit following Rastrelli's
      operation, creation of a defect of the atrial septum after Fontain's operation,
      and embolization of the coronary-cardiac fistulas and of patent ductus arteriosus
      were carried out. This review demonstrates wide use of endocardial surgery
      methods in the treatment of some congenital heart diseases; in many cases such
      treatment may be an alternative to surgical interventions.

PMID- 8578671
TI  - [Digital subtraction angiography in the diagnosis of Fallot 's tetralogy].
AB  - The authors analyze the efficacy of digital subtraction angiography (DSA) in the
      diagnosis of Fallot's tetralogy (FT); this method helps simplify and cut down the
      scope of investigations but does not deteriorate their informative value. DSA
      findings in 120 patients with TF are analyzed. The study was confined to right
      ventriculography in the majority of cases, which permitted clear-cut imaging of
      the anatomical details of the defect due to computer processing of the image.
      Morphometrical parameters were used to make assessment of involvement of the
      pulmonary artery system more objective: the ratio of the width of various
      portions of the pulmonary artery system to the width of descending aorta and the
      pulmonary arterial index characterizing the area of section of both pulmonary
      arteries in relation to body surface. The quality of imaging the stenoses and
      hypoplasia in the pulmonary artery system was high, meeting the requirements of
      present-day surgery. Moreover, DSA helps diagnose other anatomical particulars of
      TF and the concomitant defects and abnormalities, left ventricular hypoplasia and
      the type of right aortic arch among other things. The advantages of DSA in the
      diagnosis of TF are a lesser volume of catheterization, reduced number of
      sessions and of the dose of contrast agent infused at each session, better
      imaging of the anatomical details of the defect and of concomitant defects and
      abnormalities. All this permit examinations on an outpatient basis.

PMID- 8578672
TI  - [Characteristics of intracardiac hemodynamics in healthy volunteers studied by
      cine-MRI].
AB  - 15 healthy volunteers were investigated by MR to study normal intracardiac
      hemodynamic. Cine-MRI was performed on 1.5T "Magnetom SP" System. Regions of low
      signal intensity in at least cardiac chamber were found in 93%. The most frequent
      finding was a linear area of signal loss along the anterior mitral leaflet during
      diastole (86%). The distinction of normal areas of signal loss from pathologic is
      based on the extent and duration of the flow disturbance.

PMID- 8578673
TI  - [Digital subtraction ventriculography in imaging the interventricular septum of
      the heart].
AB  - A method for imaging the interventricular septum of the heart by digital
      subtraction ventriculography in the left oblique projection is proposed: 20 ml of
      contrast agent is injected in the right atrium, and the right ventricle is
      imaged, then the left ventricle is seen on the left phase. In order to discern
      the interventricular septum, the right ventricle image is taken as a "mask", then
      the left ventricle is fixed, and the interventricular septum is seen between two
      contrast cavities on the final image. The dual subtraction method by choosing the
      later "mask"-frame at the maximally contrast right ventricle for imaging the
      septum was used for the first time.

PMID- 8578674
TI  - [Rare forms of Hodgkin's disease manifestations].
AB  - X-Ray diagnosis of secondary involvement of the vertebrae in Hodgkin's disease is
      difficult because pathognomonic shadow symptoms are absent. Interpretation of
      roentgenograms is still more difficult when a soft-tissue component which may
      simulate a "cold abscess" appears in the paravertebral area. Differential
      diagnosis is based on the clinical and x-ray correlations and histologic
      findings.

PMID- 8578675
TI  - [X-ray diagnosis of the state of soft tissues in patients with achondroplasia in
      limb lengthening using Ilizarov technique].
AB  - Muscles and subcutaneous cellular tissue of upper and lower limbs have been
      studied in 14 patients with achondroplasia treated after Ilizarov in various
      periods of lengthening employing contrast roentgenography. The technique applied
      has allowed to reveal anatomic and topographic features of muscles and
      subcutaneous cellular tissue in achodroplasia cases and observe changes of
      morphological parameters in different stages of elongation.

PMID- 8578677
TI  - [Method of intravascular curving of catheters].

PMID- 8578676
TI  - [Catheter balloon valvuloplasty: new possibilities in the surgical treatment of
      mitral stenosis].
AB  - A total of 170 catheter balloon valvuloplastic (CBV) operations for rheumatic
      mitral stenosis were carried out in patients aged 19 to 68, 30 of these in
      pregnant women, at A. V. Vishnevsky Institute of Surgery, Russian Academi of
      Medical Scients, from 1988 to 1994. Characteristic features of such operations
      are a minor surgical trauma and no necessity in deep narcosis and artificial
      circulation. Analysis of the immediate results and of the data of five-year
      follow-up brings the authors to a conclusion about the efficacy of the new method
      of treatment of this heart disease and about the physiological nature of forming
      an adequate route of blood flow into the right ventricle with a balloon.
      Comparing various balloon catheters for valvuloplasty and methods to carry out
      this procedure, the authors emphasize the advantages of the instruments and
      method developed by professor V. A. Silin et al. (St. Petersburg). The
      possibility of correction of mitral stenosis by CBV in pregnant women appears to
      be particularly important. Retrospective analysis of the immediate results and
      follow-up data helped the authors not only formulate the indications for this
      intervention, but permitted them to develop an original system of comprehensive
      clinical and instrumental assessment of the degree of involvement of the mitral
      valve and subvalvular structures, and of hemodynamic disorders.

PMID- 8578678
TI  - [Experience in the use of the BRIZ-2 device for digital recording of X-ray
      television images in broncho-pulmonology].
AB  - A device is described intended for digital recording and reproduction of x-ray
      images attached to RUM-20M x-ray diagnostic complex with x-ray image
      amplification. Radiation loading of patients and the staff were reduced more than
      twofold. Spot photographs during x-ray examinations were ruled out. The quality
      of hard copies of images made using various printing devices are compared.

PMID- 8578679
TI  - [Professor P. V. Vlasov interviews Professor A. E. van Voorthuisen, Chief of the
      Department of Radiologic Diagnosis of the Leyden University Hospital (Holland)].

PMID- 8578680
TI  - Detection of tumor-associated antigens in sera of canine cancer patients by
      monoclonal antibodies generated against canine mammary carcinoma cells.
AB  - Two murine monoclonal antibodies (MAbs), 1A10 and SB2, generated against a canine
      mammary carcinoma cell line, were used in a competitive enzyme-linked
      immunosorbent assay (ELISA) to measure tumor-associated antigens (TAAs) in canine
      serum samples. Sera were tested from disease-free dogs and from dogs diagnosed
      with mammary carcinoma, non-mammary carcinoma, sarcoma, benign mammary tumor,
      benign non-mammary tumor, or non-neoplastic disease. Serum antigen concentrations
      measured by ELISA were expressed as inhibitory units (IU). The upper limit of
      normal, defined as the mean plus 2 SD of the TAA concentration in disease-free
      dogs, was 20 IU with antibody 1A10 and 22 IU with antibody SB2. Compared with
      disease-free dogs, the frequency of TAA-positive sera was significantly greater
      (P < 0.05) among dogs with mammary or non-mammary carcinoma when tested with MAbs
      1A10 or SB2, and also with sarcoma when tested with MAb SB2. Testing a serum
      sample with both antibodies rather than just one increased the sensitivity of the
      competitive ELISA for TAA detection. The presence of TAA in serum might serve as
      a useful marker for certain types of carcinomas or sarcomas in canine cancer
      patients.

PMID- 8578681
TI  - Humoral and cell-mediated immunity in natural and experimental canine
      leishmaniasis.
AB  - This paper describes immunological and clinicopathological findings in dogs
      naturally and experimentally infected with progressive visceral leishmaniasis.
      Eight dogs were intravenously inoculated with 5 x 10(7) stationary phase
      promastigotes of Leishmania infantum (LEM 2002, ZMON-1). A further eight
      naturally infected dogs were diagnosed by parasitological and serological methods
      and selected according to their clinical and immunological condition. Clinical,
      hematological, pathological and parasitological examinations, including parasite
      burden and distribution, were included in the study. Antibody production was
      estimated by means of enzyme-linked immunosorbent assay and immunofluorescence
      assay techniques; the cellular immune response was studied by means of the skin
      test and the lymphocyte proliferation test. Experimentally infected dogs
      developed a chronic and progressive disease with the same clinical signs shown by
      naturally infected dogs. Both naturally and experimentally infected dogs
      developed the same histopathological reaction, but to differing degrees. Parasite
      burden and distribution were related to the extent of lesions, and were
      consequently less pronounced in experimentally infected dogs. The main feature of
      the immune response in experimental and natural infection was the lack of
      specific T-cell response to leishmanial antigen. Non-specific responses to
      mitogens were normal (i.e. as compared with healthy dogs) throughout the
      experimental infection, but were partially suppressed (65.3%) in naturally
      infected animals. A remarkable humoral response was evident in both natural and
      experimental infection: IgG-isotype antibodies were detected in experimental
      infection at 50-70 days post infection, and their production increased during the
      course of the infection. However, high titers were observed only in naturally
      infected dogs.

PMID- 8578682
TI  - Molecular cloning of equine interleukin-1 alpha and -beta cDNAs.
AB  - Equine interleukin-1 alpha (IL-1 alpha) and IL-1 beta were molecularly cloned to
      establish a basis for research on inflammatory and immune responses in the horse.
      Equine peripheral blood mononuclear cells (PBMC) were stimulated with
      lipopolysaccharide (LPS), and cDNA clones of equine IL-1 alpha and IL-1 beta
      covering the whole coding sequences were isolated from them. These equine IL-1
      alpha and IL-1 beta clones contained open reading frames encoding 271 and 269
      amino acids, respectively. The deduced amino acid sequence of equine IL-1 alpha
      showed 71.6% and 60.2% similarity with that of human and murine IL-1 alpha,
      respectively. Similarly, the amino acid sequence of equine IL-1 beta showed 66.7%
      and 61.8% similarity with that of human and murine IL-1 beta, respectively. In
      both equine IL-1 alpha and IL-1 beta, amino acids at miristoylation sites were
      well conserved. Dot blot analysis indicated that the expression of IL-1 beta was
      predominant to that of IL-1 alpha in equine PBMC stimulated with LPS or phorbol
      myristate acetate.

PMID- 8578683
TI  - Experimental mucosal disease in cattle: changes of lymphocyte subpopulations in
      Peyer's patches and in lymphoid nodules of large intestine.
AB  - Changes in the number and distribution of lymphocyte subtypes were investigated
      in Peyer's patches in the jejunum and ileum, and mucosa-associated lymphoid
      nodules in the proximal colon and rectum of cattle with end-stage mucosal
      disease. Mucosal disease had been induced experimentally in seven of 13 animals
      by inoculation with cytopathogenic bovine viral diarrhea virus (cp BVD-virus).
      For comparison, six clinically healthy, persistently viremic cattle were used.
      IgM+, IgA+, BoCD4+, BoCD8+ and gamma delta TCR+lymphocytes, and the cp BVD-viral
      antigen were visualized in tissue sections by immunohistochemistry. In cattle
      with mucosal disease, the size of lymphoid follicles was significantly decreased
      in all localizations resulting in decreased numbers of B-lymphocytes per average
      follicular area. In most animals domes were missing and epithelium was
      invaginated into the lymphoid follicles. Numbers of BoCD4+ and BoCD8 + T
      lymphocytes were increased per mm2 of lymphoid follicle. Conversion of these
      counts into number of cells per average follicular area revealed, however, that
      the absolute number of BoCD4 + T-lymphocytes had decreased within lymphoid
      follicles and there was no distinct change of BoCD8 + T-lymphocytes in comparison
      to the controls. Interfollicular areas were less densely populated due to reduced
      numbers of BoCD4 + and BoCD8 + T-lymphocytes. cp BVD-viral antigen was detected
      predominantly in epithelial cells and in cells with dendritic morphology within
      lymphoid follicles. This may indicate that the severe depletion of B-lymphocytes
      in the lymphoid follicles is due to alterations of the microenvironment. The
      decrease of BoCD4 + and BoCD8 + T-lymphocytes does not support the hypothesis of
      T-cell-mediated tissue damage. Destruction of mucosa-associated lymphoid nodules
      does not only lead to local disruption of the gastrointestinal barrier, but will
      reduce the seeding of effector cells to the mucosa and therefore impair the
      defense mechanisms of the gastrointestinal barrier.

PMID- 8578684
TI  - Phenotypic analysis of peripheral blood lymphocytes and intestinal intra
      epithelial lymphocytes in calves.
AB  - The phenotype of intestinal intraepithelial lymphocytes (IEL) of young calves has
      not been described. In order to determine the potential role of IEL in protection
      against enteric infection, it is important to characterize these cells in normal
      calves. Therefore, IEL of calves were analyzed phenotypically and compared with
      peripheral blood lymphocytes (PBL) via flow cytometry using monoclonal antibodies
      to cell surface markers. Approximately 25% of PBL and IEL expressed the
      gamma/delta T-cell receptor (TCR-1+). TCR-1+ PBL co-expressed WC1 (antigen
      expressed on a subset of lymphocytes expressing the gamma/delta T-cell receptor),
      whereas only a small percent of TCR-1+ IEL co-expressed WC1. TCR-1+ cells in the
      PBL co-expressed the interleukin-2 receptor (IL-2r), whereas TCR1+ cells in the
      IEL co-expressed ACT-2 (null cell and CD-8+ T-cell activation marker). There were
      approximately twice as many CD-4+ cells as CD-8+ cells in the PBL, whereas there
      were three to five times as many CD-8+ cells as CD-4+ cells in the IEL. Thus, IEL
      of calves are antigenically distinct from PBL.

PMID- 8578685
TI  - Quantitation of transforming growth factor-beta in plasma and pulmonary
      epithelial lining fluid of sheep experimentally infected with maedi-visna virus.
AB  - A model of experimental infection with EV1, a lytic British isolate of maedi
      visna virus (MVV), was developed. Ten Texel sheep were allocated to two groups
      and inoculated by the respiratory route with different inocula. Six of the
      animals received 10(7.2) TCID50 (tissue culture infective dose) of EV1 strain,
      while four sheep were sham-inoculated with identically prepared virus-free buffer
      solution. Experimental infection was followed for 8 weeks post-inoculation (PI),
      with development of precipitating antibodies to MVV developed in the MVV
      inoculated animals during the first 4 weeks PI. Transforming growth factor-beta
      (TGF-beta) levels, in both bronchoalveolar lavage fluid supernatant and plasma
      samples, were measured. Concentrations of pulmonary epithelial lining fluid
      (PELF) TGF-beta were calculated. TGF-beta concentrations in PELF were
      approximately 165-fold higher than in plasma. No significant differences in the
      concentrations of plasma or PELF TGF-beta, either within or between groups, were
      observed.

PMID- 8578686
TI  - Ovine mast cell heterogeneity is defined by the distribution of sheep mast cell
      proteinase.
AB  - The presence or absence of the granule chymase, sheep mast cell proteinase
      (SMCP), was determined in trachea, bronchus, bronchial lymph node, lung, thymus,
      spleen, liver, flank skin, abomasum, duodenum, jejunum, ileum, colon and
      mesenteric lymph node by immunohistochemistry and by enzyme-linked immunosorbent
      assay using a polyclonal, affinity purified anti-SMCP antibody. Additionally, the
      presence of putative ovine mast cell subsets was investigated by comparing the
      number of mast cells identified histochemically (toluidine blue pH 0.5) with the
      number detected by immunostaining. The thymus had the greatest density of mast
      cells (225.7 +/- 23.4 cells mm-2, histochemically) and the highest concentration
      of SMCP (19.7 +/- 9.3 micrograms SMCP g-1 wet tissue). There was a high degree of
      correlation between toluidine blue and anti-SMCP cell counts for all tissues (r2
      = 0.96, P < 0.001) with the exception of skin and liver. On the basis of
      reactivity to the anti-SMCP antibody, two populations of mast cells were defined,
      notably those in gastrointestinal tissues (analogs to the mucosal mast cell
      subset) and those present in skin (the putative ovine connective tissue mast cell
      subset). Ovine mast cell heterogeneity, resulting from differential expression of
      SMCP, was thus confirmed.

PMID- 8578687
TI  - Production and characterisation of ovine GM-CSF expressed in mammalian and
      bacterial cells.
AB  - A cDNA encoding ovine granulocyte-macrophage colony-stimulating factor (GM-CSF)
      was isolated and two forms of recombinant ovine GM-CSF were produced. A
      glycosylated form was produced in mammalian cells infected with a recombinant
      vaccinia virus encoding ovine GM-CSF. Recombinant ovine GM-CSF was also produced
      in Escherichia coli and purified by affinity chromatography. Both forms of the
      protein were detected by ovine GM-CSF-specific monoclonal antibodies, and
      exhibited activity on ovine bone marrow haemopoetic progenitor cells.

PMID- 8578688
TI  - Immunohistological study of the cutaneous delayed type hypersensitivity reaction
      in sheep.
AB  - The cutaneous delayed type hypersensitivity (DTH) reaction may be experimentally
      initiated both as an in-vivo technique for the study of the cell mediated arm of
      the immune system, and also as an accurate clinical test of the functional
      capacity of this part of the immune response. This study was performed to fully
      evaluate the immunohistological characteristics of the normal DTH reaction
      utilising an ovine model. Six clinically healthy sheep were inoculated with an
      intradermal Mycobacterium bovis vaccine. After 21 days, they were challenged with
      multiple intradermal injections of a purified protein derivative (PPD) of M.
      bovis in the hairless skin of the medial thigh. Simultaneous contralateral
      injections of sterile diluent were performed to provide control material. The
      resulting lesions were measured for increase in skin thickness and biopsied at 2,
      7, 24, 48, 72, and 96 h post injection. The biopsies were divided, and stained
      both histochemically and with monoclonal antibodies directed against lymphocyte
      subsets, macrophages, and B cells. The DTH reaction was maximal at 72 hours post
      challenge, and was largely characterised by an initial influx of
      polymorphonuclear neutrophil (PMN) cells, after which there was an accumulation
      of alpha beta T cells. The number of macrophages within the lesion declined with
      the progression of the reaction. B cells and gamma delta T cells did not appear
      to play a major role in the response. Fibrin was a marked component of the
      reaction at later time points.

PMID- 8578689
TI  - Nested PCR allows the characterization of TaqI and PstI RFLPs in the second exon
      of the caprine MHC class II DRB gene.
AB  - A nested polymerase chain reaction (PCR) method has been developed to obtain a
      specific amplification of the second exon of the caprine MHC class II DRB gene.
      The specificity of this method has been verified by cloning and sequencing the
      PCR product and comparing its sequence to 21 previously published caprine DRB
      second exon allelic variants. Nucleotide identity between this sequence (Caae
      DRB23) and other caprine DRB alleles ranged between 85.6% (Caae-DRB22) and 96.5%
      (Caae-DRB5). Caae-DRB5 and Caae-DRB23 sequences diverged in five amino acid
      substitutions (70, 71, 73, 74, 78), all of them placed at the antigen binding
      site. Likewise, the restriction polymorphism of the caprine DRB second exon has
      been analyzed and two different restriction patterns have been found depending on
      the presence or absence of a TaqI site and a PstI site at positions 122 bp and
      241 bp of the PCR product respectively. TaqI and PstI RFLPs were also analyzed in
      other artiodactyla species. While PstI RFLP was found not only in goats but also
      in cattle, sheep and pigs, TaqI RFLP was only detected in goats. In all of these
      species close associations were detected between the presence of TaqI and PstI
      restriction sites and amino acid substitutions at positions 40 and 78
      respectively, suggesting that PCR restriction fragment length polymorphism (RFLP)
      could be a useful tool in relating amino acid substitutions at critical positions
      with disease resistance.

PMID- 8578690
TI  - Humoral and cellular responses following local immunization with a surface
      antigen of the gastrointestinal parasite Haemonchus contortus.
AB  - A purified, larval specific antigen of the abomasal parasite Haemonchus contortus
      was used to immunize sheep. In an attempt to induce a local immune response in
      the abomasum, the antigen was injected twice into the abomasal wall after one
      peripheral immunization. Serum antibody responses were boosted by each intra
      abomasal immunization but not by the challenge infection given 3.5 weeks after
      the last immunization. Examination of the specific antibody secreting cells (ASC)
      recirculating in the peripheral blood indicated that there was an increase in
      blood ASC 5 days after local stimulation. This increase was maintained only after
      immunization and not after infection, probably reflecting the different responses
      induced when antigen is presented by injection in an adjuvant or by the parasite
      during infection. High proliferative T cell responses in the abomasal lymph nodes
      were only observed in one of the five sheep immunized with antigen; this was also
      the only sheep in this group to maintain an adult parasite burden at postmortem
      corresponding with the lowest antibody response. Peak faecal egg counts after
      infection were reduced by 54% in the immunized group compared to control sheep.
      Egg counts in the control sheep were, however, variable and dropped quickly,
      probably as a consequence of the inflammatory response induced by the injection
      of aluminium hydroxide into the abomasal wall.

PMID- 8578691
TI  - Effects of orally administered Clostridium butyricum MIYAIRI 588 on mucosal
      immunity in mice.
AB  - The activation of local mucosal immunity by Clostridium butyricum MIYAIRI 588
      (CBM588) was investigated in germ-free mice. An increase of polyclonal IgA
      production in the small intestine or secretion into the intestinal lumen was
      observed in mice mono-associated with CBM588 and fed a diet containing killed
      vegetative cells of CBM588 (VCBM). However, fecal IgA of anti-CBM588 was rarely
      formed in mice administered CBM588 during 6 weeks from administration. Cholera
      toxin was administered orally to SPF mice fed a diet containing CBM588, and IgA
      secretion of anti-cholera toxin was enhanced in mice fed a VCBM diet. In
      addition, the production of IgA, IgM and IgG in Peyer's patch cell culture was
      increased in the presence of VCBM. These results suggest that oral administration
      of CBM588 stimulates polyclonal mucosal immune activity and shows adjuvant
      activity for anti-cholera toxin.

PMID- 8578692
TI  - Efficacy of a live Cryptobia salmositica vaccine, and the mechanism of protection
      in vaccinated rainbow trout, Oncorhynchus mykiss, against cryptobiosis.
AB  - An attenuated strain of Cryptobia salmositica was used as a live vaccine to
      protect rainbow trout, Oncorhynchus mykiss, against cryptobiosis. Fish immunized
      with 1.0 x 10(4) or 5.5 x 10(4) attenuated C. salmositica per fish were protected
      3 weeks after immunization; however, this period was reduced to 2 weeks if fish
      were vaccinated with 1.0 x 10(5) attenuated parasites per fish. Fish were still
      protected at 6, 12 and 24 months after vaccination. Complement fixing antibodies
      in the blood of immunized fish lysed C. salmositica under in vitro conditions.
      The titre of complement fixing antibodies in vaccinated fish increased rapidly 1
      2 weeks post-challenge. In vitro phagocytosis was enhanced by antiserum and by
      activated macrophages from vaccinated fish. There was also evidence of antibody
      independent and antibody dependent cell-mediated cytotoxicity in vaccinated fish.

PMID- 8578693
TI  - Investigations into the ubiquitous nature of high or low immune responsiveness
      after divergent selection for antibody production in common carp (Cyprinus carpio
      L.).
AB  - This paper reports on the selection of individual carp with a high or low
      antibody response, in combination with reproduction by gynogenesis, in order to
      develop well-characterised inbred carp lines consisting of practically unlimited
      numbers of carp with the same genotype. Two homozygous progenies, previously
      characterised as having a high or low immune response to dinitrophenyl keyhole
      limpet haemocyanin (DNP-KLH), were immunised with either a T-dependent (DNP-human
      serum albumin (DNP-HSA)) or T-independent (trinitrophenyl lipopolysaccharide (TNP
      LPS)) hapten-carrier complex. In comparison with the antibody response after DNP
      KLH immunisation, the response to DNP-HSA was observed to be highly variable and
      did not differ between the divergently selected progenies. This suggests that the
      divergent selection for antibody production to DNP-KLH has been carrier-specific.
      Immunisation with T-independent TNP-LPS induced a very rapid response which
      differed between the high and low responders, and likely measured changes in the
      DNP-specific precursor pool of B cells caused by the selection. A number of
      selected individuals with a high immune response to DNP-KLH were infected with
      Trypanoplasma borreli, a haemoflagellate parasite of carp, to examine a possible
      relationship between the increase in immune responsiveness and disease
      resistance, but no change could be detected. However, individual homozygous carp
      were able to escape inbreeding depression and survive the infection. Such carp
      would be likely candidates for gynogenetic reproduction to obtain viable inbred
      carp lines.

PMID- 8578694
TI  - Effect of the microsporidian Enterocytozoon salmonis on the immune response of
      chinook salmon.
AB  - The protozoan parasite Enterocytozoon salmonis is an intranuclear microsporidian
      of salmonid mononuclear leukocytes. Experimental infections were initiated in
      chinook salmon to determine the effects of parasitism on selected host immune
      functions. The humoral antibody response to dinitrophenylated-keyhole limpet
      hemocyanin and the in vitro blastogenic responses of isolated mononuclear
      leukocytes to mitogens (concanavalin A, lipopolysaccharide and phytohemagglutinin
      P) were evaluated. The humoral response as detected by enzyme-linked
      immunosorbent assays was suppressed following infection. The degree of
      suppression increased as the severity of the infection progressed. Additionally,
      the response to mitogen-induced lymphoproliferation was impaired. These results
      suggest that infection with E. salmonis may cause suppression of host cell immune
      functions, thus increasing the susceptibly of infected fish to other pathogens.

PMID- 8578695
TI  - [The effect of long-term treatment of arterial hypertension with Ca antagonists
      on the renin-angiotensin-aldosterone system in diabetics. Hyporeninemic
      hypoaldosteronism].
AB  - During long-term treatment of arterial hypertension with calcium antagonists of
      the dihydropyridine type activation of the sympathetic nervous system and
      subsequently also of the renin-angiotensin-aldosterone system persists, while the
      haemodynamic reaction to vasodilatation, manifested by an elevated pulse rate and
      minute volume from the initial stage of therapy, recedes. In type II diabetics
      the basal and stimulated response of the renin-angiotensin-aldosterone system is
      reduced. The administration of calcium antagonists of the dihydropyridine type
      does not stimulate significantly the renin-angiotensin-aldosterone system as the
      starting function of the sympathetic nervous system is impaired within the
      framework of vegetative neuropathy. In almost 20% NIDDM plasma renin activity and
      aldosterone do not respond to furosemide administration and the vertical posture.
      In others the response is found but takes place at reduced levels. Hyporeninaemic
      hypoaldosteronism is thus manifested not so much by a drop of plasma renin and
      aldosterone beneath the lower range of reference values as by a reduced response
      to stimulation. Functional hyporeninaemic hypoaldosteronism is another, frequent
      late complication of diabetes. In advanced forms a further block of the renin
      angiotensin-aldosterone system by ACE inhibitors can then produce, even in the
      absence of diabetic nephropathy, in the stage of chronic renal failure dangerous
      hyperkaliaemia which may threaten the patient. Dynamic examination of the
      sympathetic nerve and the renin-angiotensin-aldosterone system makes it possible
      to predict this condition. In practice it is necessary in diabetics with arterial
      hypertension after starting with ACE inhibitors during the first days to monitor
      repeatedly plasma potassium and creatinine. ACE inhibitors and calcium
      antagonists are otherwise for diabetics drugs of first choice which can arrest
      the progression of nephropathy, effectively reduced the blood pressure without
      causing deterioration of insulin resistance and hyperlipoproteinaemia and lead
      even to regression of hypertrophy of the vascular wall and left ventricle.

PMID- 8578696
TI  - [Neurohumoral activity in liver cirrhosis].
AB  - The authors assessed in 40 patients with cirrhosis of the liver and in 33
      controls the plasma renin activity (PRA), aldosterone (PA), the atrial
      natriuretic factor (ANF) and the digoxin like activity (DLA) in plasma under
      basal conditions. In patients with cirrhosis of the liver they found
      significantly lower levels of PRA, PA and DLA, as compared with the control
      group, the ANF levels were not significantly altered. In the group with cirrhosis
      the highest neuroendocrine activity was recorded, in particular of PRA and PA in
      decompensated cirrhotics receiving diuretic treatment. Therefore it is useful to
      combine diuretics with preparations or measures which reduce the activity of the
      renin-angiotensin-aldosterone system and/or promote the activity of natriuretic
      substances. The authors found a negative correlation between PRA and SNa, PRA and
      UNaV, while ANF did not correlate with natriuresis. The main determinant of Na
      excretion in decompensated cirrhosis is the activity of the renin-angiotensin
      aldosterone system. DLA plasma levels also correlated inversely with SNa values
      and Na excretion and thus also reflect the severity of fluid retention.

PMID- 8578697
TI  - [Safety of hormone replacement therapy in menopause and its favorable effect on
      the lipid spectrum].
AB  - The authors pay attention to changes of the serum lipid spectrum and blood sugar
      level during hormonal substitution treatment of menopausal women. The observation
      pertains to 70 women (mean age 50 years, 36 women after hysterectomy, mean
      duration of the menopause 4.5-5.0 years). The lipid spectrum and blood sugar
      level were assessed by enzyme methods from venous blood collected in the morning
      on fasting before administration of treatment (a combination of oestrogen and
      gestagen), on average after 8 months on these drugs. With regard to total
      cholesterol and HDL-cholesterol before treatment the women were, consistent with
      recommendations of the European Society for Atherosclerosis divided into four
      groups: hypercholesterolaemic group (5.2-7.8 mmol/l) 47 women;
      hypercholesterolaemic group with a reduced HDL-cholesterol (less than 1.1 mmol/l)
      5 women; a very high cholesterol group (more than 7.8 mmol/l) one woman only; and
      women with a normal lipid profile (total cholesterol less than 5.2 mmol/l), 17
      women. The authors recorded in the whole group a significant drop of total
      cholesterol (-0.30 mmol/l), VLDL-cholesterol (-0.08 mmol/l) and triacylglycerols
      (-0.27 mmol/l) and a significant rise of HDL-cholesterol (+0.13 mmol/l). The
      blood sugar level did not change. There was an insignificant drop of LDL
      cholesterol. Hepatic serum enzymes did not change during this treatment. The most
      marked changes (a drop of LDL-cholesterol by 0.49 mmol/l and rise of HDL
      cholesterol by 0.29 mmol/l) were recorded in the group with the highest risk,
      i.e. group 2. The total drop of triacylglycerols was striking. The body weight
      and dietary habits did not change during the mentioned 8-month period. The
      authors consider hormonal replacement therapy indicated. They emphasize its
      favourable effect on the lipid spectrum of women which is one of the mechanisms
      of cardiovascular oestrogen protection.

PMID- 8578698
TI  - [Etofylline clofibrate in the treatment of diabetic dyslipidemia: results of a 6
      month period of therapy].
AB  - The objective was to investigate the tolerance of ethophylline clofibrate (EPC)
      and its effectiveness on changes of dyslipidaemia and compensation of diabetes in
      type II diabetics during six-month administration of the preparation Duolip forte
      (Merckle). Twenty diabetics with dyslipoproteinaemia IIb and IV according to
      Frederickson's classification, compensated by diet alone or combined with oral
      antidiabetics (Glucobene, Merckle) were included in the study consecutively
      according to uniform basal criteria. The selected hypolipidaemic agent was
      administered to patients according to the following pattern: the first four weeks
      1,000 mg (2 tablets in the evening) the next two weeks 1.5 tablets and then till
      the end of the investigation 1 tablet in the evening. In all patients treatment
      with EPC led to a significant reduction of the total cholesterol level (CH) at
      all time intervals. Changes of ApoB, ApoA1 and Lp(a) serum levels did not attain
      statistical significance but trends were revealed (e.g. a drop of the ApoB/ApoA1
      index) which are consistent with the expected favourable action of EPC on the CH
      distribution in lipoproteins. The triacylglycerol (TG) serum concentration
      declined significantly already after one month of treatment and after
      identification of five patients whose TG were distributed in separate clusters
      the hypotriacylglycerolaemic effect of EPC persisted still three months after
      treatment. It may be summarized that treatment of dyslipoproteinaemia of the type
      II diabetics with ethophylline clofibrate (Duolip forte, Merckle) led a) to a
      marked reduction (13-15%) of serum cholesterol, which b) diminished (to 8-9%) but
      persisted still after 6 months of treatment, c) the greatest effect of EPC on the
      TG serum level was observed one month after treatment, d) all improvements of
      lipid parameters occurred without affecting the compensation of diabetes, or BMI
      and were not associated with any side-effects of EPC.

PMID- 8578699
TI  - [Treatment of chronic myeloid leukemia with bone marrow transplantation at the
      Institute of Hematology and Blood Transfusion in Prague].
AB  - The outcomes of bone marrow transplantation (BMT) performed at the Institute of
      Haematology and Blood Transfusion from April 1988 to December 1994 in 31 patients
      with chronic myelogenous leukemia are presented. Age of the patients range from
      18 to 49 years, median 34 years. Male:female ratio was 1.58:1. The conditioning
      regimen consisted of Cyclophosphamide and total body irradiation (TBI) or
      Busulfan and Cyclophosphamide. The results are evaluated as of January 1, 1995.
      Nineteen patients (61.3%) are alive, 12 patients (38.7%) died. The causes of
      death are discussed. The median time of follow up all patients is 10.4 months,
      range 0.3-81.5. The median time of follow up of surviving patients is 21.8
      months, range 2.5-81.5. Probability of 2 years survival by Kaplan-Meier analysis
      is 58 +/- 10%. Of the 24 transplanted in the first chronic phase, 18 patients are
      alive. Of the 7 transplanted in advanced phase of the disease, 1 patient is
      alive. Of the 27 patients, who received bone marrow from an HLA identical
      sibling, 19 are alive. Of the 4 patients who received bone marrow from other
      donor than an HLA identical sibling, none is alive. Acute GvHD III.-IV. grade
      developed in 5 patients (16.1%), moderate and severe chronic GvHD developed in 11
      patients (31.5%). Cytogenetic relapse was diagnosed in 1 patient, hematological
      relapse in 2 patients. Karnofsky scores of patients surviving after BMT range
      from 30% to 100%, median 90%.

PMID- 8578700
TI  - [Successful prevention of Pneumocystis carinii infection with 1,920 mg of
      trimethoprim-sulfamethoxazole daily in patients with malignant hematopoietic
      diseases].
AB  - During 1991-94 we treated 51 patients with acute myeloid leukaemias and 3
      patients with a myelodysplastic syndrome of refractory anaemia with excess of
      blasts in transformation. The patients received trimethoprim-sulphamethoxazole
      (TMP-SMX) 1,920 mg daily as a prophylaxis of Pneumocystis carinii infections and
      selective decontamination of gastrointestinal tract. The majority of patients
      received TMP-SMX in their first course of chemotherapy with daunorubicin and
      cytosine arabinoside. Only one of the 18 patients without TMP-SMX prophylaxis
      during the first course of chemotherapy developed Pneumocystis carinii pneumonia.
      That pneumonia was successfully treated by intravenous administration of TMP-SMX
      1920 mg four times a day. No other Pneumocystis carinii infection was encountered
      in all other patients during their clinical follow up or in autopsy material of
      expired patients. TMP-SMX prophylaxis had to be interrupted in 11 patients due to
      their suspicious allergic skin reactions, however, TMP-SMX was readministered in
      all without any skin changes attributable to TMP-SMX during next cycles of
      chemotherapy. TMP-SMX in a given daily dose of 1,920 mg seems to be a successful
      prophylaxis of Pneumocystis carinii infections in patients with malignant
      diseases of hematopoiesis.

PMID- 8578701
TI  - [G-CSF (Neupogen Roche) in the treatment of patients with chronic aplastic anemia
      with severe neutropenia].
AB  - Aplastic anaemia (AA) of the chronic type with severe cytopenia is very
      frequently a difficult therapeutic problem. Patients with granulocyte values
      below 0.5 G/l are threatened by infections, incl. sepsis possibly with a fatal
      outcome. If the pool of stem cells for granulocytes is not completely exhausted
      and can respond to growth factors, these patients can be treated either
      chronically and/or in risk situations (e.g. injury, surgery) with preparations of
      the type of a recombinant, granulocyte colony stimulating factor (rhG-CSF), or
      granulocyte and monocyte colony stimulating factor (rhGM-CSF). The authors
      present a review of diagnostic and therapeutic algorithms in patients with the AA
      syndrome and summarize their own experience with the preparation Neupogen Roche
      (rhG-CSF).

PMID- 8578702
TI  - [Cortisol and diseases of the gastrointestinal tract].
AB  - Cortisol is the hormone reacting to endogenous and exogenous stress. An important
      role is ascribed to stress in the genesis and development of malignant and
      inflammatory diseases of the GIT. The authors examined in their investigation the
      24-hour secretion of cortisol in patients with gastric affections, polyps of the
      large bowel and compared them mutually and with groups of patients with
      ulcerative colitis and healthy probands. In all investigated groups a 24-hour
      rhythm of cortisol secretion was confirmed. The only significant difference
      between the investigated groups was a lower 24-hour amplitude in patients with
      ulcerative colitis, as compared with healthy probands. The results do not suggest
      a significant role of cortisol in the development of premalignant diseases of the
      GIT.

PMID- 8578703
TI  - [Determination of differential renal function using dynamic scintigraphy].
AB  - By examination of 71 patients, using static and dynamic scintigraphy of the
      kidneys, the authors tested whether dynamic scintigraphy provides correct results
      of the separate renal function in case of a symmetrical localization of the
      kidneys. In case of slight asymmetry the error of calculation is feasible. In
      case of major differences in the position of the kidneys the results cannot be
      used for clinical purposes. In these patients static scintigraphy must be used
      with correction for different absorption layers.

PMID- 8578704
TI  - [Congenital dyserythropoietic type II anemia complicated by extramedullary
      hematopoiesis in the posterior mediastinum].
AB  - In a 48-year-old woman investigated on account of congenital dyserythropoietic
      anaemia type II (HEMPAS) on the X-ray of the chest a polycystic sharply defined
      shadow in the posterior mediastinum was detected and extramedullary
      haematopoiesis was suspected. The diagnosis was confirmed cytologically.
      According to the authors' knowledge this is the second case of this rare
      complication in CDA-II in the world and the second case of EMH in the mediastinum
      in this country. In the discussion the authors summarize the diagnostics of
      congenital dyserythropoietic anaemias. They discuss also the pathogenesis of
      extramedullary haematopoiesis, diagnosis and differential diagnosis of EMH in the
      posterior mediastinum, possible complications and treatment.

PMID- 8578705
TI  - [Coronary heart disease with a marked vasospastic component associated with the
      menstrual cycle and its treatment].
AB  - The authors describe the case of a 46-year-old patient with serious
      manifestations of ischaemic heart disease-repeated myocardial infarctions,
      malignant arrhythmias, the algic form of angina pectoris, whose complaints were
      markedly linked to the menstrual cycle. The authors mention also the individual
      solution, i.e. elimination of ovarian activity by actinotherapy.

PMID- 8578706
TI  - [Biological effects of allogenic leukocytes and leukocyte-depleted blood cell
      products].
AB  - The use of leukodepleted cellular blood components may reduce some adverse effect
      of transfusion in certain indications. This review presents the adverse effects
      of contaminating donor leukocytes in blood components: alloimmunisation, febrile
      nonhemolytic transfusion reactions, refractoriness to platelet transfusions,
      graft versus host disease, transmission of leukotropic infections and
      immunomodulation. The value of leukodepletion in preventing some of these
      complications, methods of leukodepletion and the current indications of use of
      leukodepleted components in clinical practice are discussed.

PMID- 8578707
TI  - [Endogenous digitalis-like substance. II. Relation to pathologic states and
      diseases].
AB  - Endogenous digitalis-like substances (EDLS) may play an active but differential
      role in numerous physiological and pathophysiological mechanisms. Reviewed are
      diseases, in which EDLS could be considered to play a causative role in their
      pathogenesis. Relations of EDLS were described mainly to cardiovascular,
      endocrine and metabolic diseases. Existence of EDLS, however, may have also
      another clinical implications which include possibility of influencing of digoxin
      monitoring as well as effects of digoxin therapy. Finally, methods of detection
      of EDLS are reviewed.

PMID- 8578708
TI  - [Extracorporeal elimination of LDL-cholesterol in the treatment of
      hypercholesterolemia: indications and methods].
AB  - Extracorporeal elimination of LDL-cholesterol is at present an important part of
      comprehensive treatment of patients with very high cholesterol levels. An
      absolute indication for their use are patients with the homozygous form of
      familial hypercholesterolaemia. Treatment is, after individual consideration,
      indicated also patient with severe heterozygous familial hypercholesterolaemia,
      with a positive family history of IHD, if it is not possible to reduce LDL
      cholesterol by diet and hypolipidaemic agents below 5.2 mmol/l; also patients
      with severe IHD and severe hypercholesterolaemia, included in secondary
      prevention where it is not possible to reduce LDL-cholesterol by diet and
      pharmacotherapy below 3,4 mmol/l. Another indication for treatment by LDL
      apheresis are patients where cardiosurgery cannot be performed because of
      angiosclerosis. These are patients with severe hypercholesterolaemia which does
      not respond to drugs and with diffuse changes of the coronary circulation in
      young age, which cannot be treated by angioplasty or coronary bypass, and also
      patients after a coronary bypass with a refractory disorder of the lipid
      metabolism. LDL apheresis is furthermore indicated in patients with severe
      hyperlipidaemic crises which eventually develop into necrosis of the pancreas.
      Long-term LDL-apheresis leads to regression of manifestations of xanthomatosis of
      the skin and tendons, it prevents progression and starts regression of
      atherosclerosis in patients with severe hypercholesterolaemia. In homozygotes
      with familial hypercholesterolaemia treatment by LDL-apheresis leads to
      prolongation of life and improves the quality of life. In heterozygotes neither
      prolongation of the life span nor a lower incidence of IHD is observed, while the
      quality of life improves and regression of atherosclerosis occurs. A combination
      of LDL-apheresis, dietary provisions and hypolipidaemic treatment in
      heterozygotes is the most effective method to reduce the LDL-cholesterol level.
      Extracorporeal elimination of LDL-cholesterol can be done by non-selective
      centrifuging or membrane plasmapheresis. More recent methods of LDL-apheresis are
      more selective and effective. They use active columns or capsules to remove
      atherogenic particles from plasma. These methods include cascade filtration,
      immunoadsorption heparin-induced LDL precipitation, thermofiltration and dextran
      induced LDL precipitation.

PMID- 8578709
TI  - [Assuring care of diabetics in the Czech Republic. Recommendations of the Czech
      Diabetes Society].

PMID- 8578711
TI  - [The improvement in the delivery of medical care to the wounded in war].

PMID- 8578710
TI  - [New principles in the prognosis, diagnosis, prevention and treatment of the DIC
      syndrome].
AB  - In accordance with the proposed methodics the state of Hageman factor (HF) system
      was studied, i.e. intimate connection of callicrein-kinine, coagulation and
      fibrinolytic blood systems in various clinic and hemostasiological forms of DIC
      syndrome, acute and chronic arterial thromboses, thrombembolisms, post-operative
      and thrombolytic hemorrhages in 1118 patients. The author describes the
      principles of diagnosis, prophylaxis and correction of the disorders in blood
      coagulation, fibrinolysis and kinogenesis in this pathology. The article contains
      data concerning the structure of researches, index and HF coefficients, as well
      as reference hemostasiological criteria, classification and medical tactics in
      various forms of DIC-syndrome.

PMID- 8578712
TI  - [The problem of cytomegalovirus infection in military blood transfusions].
AB  - The actuality of a problem of cytomegaloviral infection in military
      transfusiology is substantiated by the increasing number of immunocompromised
      recipients, mass use of hemocomponent therapy in prophylaxis and correction of
      anemia, thrombohemorrhagic and immunodeficient syndromes. Cytomegaloviral
      infection in the recipients of hemocomponents may have unfavourable consequences,
      such as the development of mononucleosis, enhanced sensitivity to opportunistic
      infectious agents as a result of virus-induced immunodepression, graft rejection,
      risk of the development of oncologic diseases, atherosclerosis, disorders in the
      processes of reparation and regeneration. In the northwestern part of Russia the
      cytomegaloviral antigens are disclosed in 65-75% of men, age 18-23. Actual tasks
      are the following: put into practice cytomegaloviral antigens test for donors,
      make a wide use of effective leukocytic filters for leukocyte removal from
      hemotransfusional medium, minimize posttransfusion immunosuppression, determine
      recipients who need transfusions of hemocomponents prepared from seronegative
      donors.

PMID- 8578713
TI  - [Postoperative progressive peritonitis in patients wounded in the abdomen].

PMID- 8578714
TI  - [A trial of the use of the nondepolarizing muscle relaxant isocyuronium bromide
      in anesthesiology].

PMID- 8578715
TI  - [Hypobaric hypoxia in the treatment of chronic anemia].
AB  - The article studies the possibilities of adaptation for hypoxia in the conditions
      of decompressive barochamber for treatment of patients with asiderotic anemia.
      The high efficiency of hypobaric hypoxia was marked in treatment of these
      patients in medical stationary and during pre-operational management of
      gynaecological patients. In the process of adaptation for hypoxia these patients
      had an increase in hemoglobin contents, enhanced functional reserves of
      cardiorespiratory system, and growth of performance capability. After adaptation
      for hypoxia these patients have passed throughout postoperative period with less
      difficulty.

PMID- 8578717
TI  - [Mobile forces: the organizational bases for managing the medical service].

PMID- 8578716
TI  - [The addictive behavior of servicemen under combat conditions].
AB  - On the basis of the analysis of literature the authors make a correction in the
      significance of terms "addiction" and "addictive behaviour", making from them a
      single notion "additive disorders". The article analyses the problem of addictive
      disorders which occupied an important place among psychiatric casualties in the
      40th Army during the war in Afghanistan. The comparison of this experience with
      the experience of the US Army in Korea and Vietnam gave the possibility to come
      to a conclusion that addictive disorders were an important medico-social problem
      for modern local wars. Its subdivision into addictive behaviour and narcomanic
      pathology lead to a necessity to revise some aspects in psychiatric care to
      servicemen in wartime period.

PMID- 8578718
TI  - [The nosological characteristics of infectious patients requiring intensive
      therapy].

PMID- 8578719
TI  - [The biological effects of combined exposure to radiation and chemical factors
      (experimental research)].

PMID- 8578720
TI  - [The causes of the loss of consciousness during diving].

PMID- 8578721
TI  - [The training of specialists for the medical service of the Red Army on the eve
      of and during World War II (1)].

PMID- 8578722
TI  - [The Saint-Petersburg Admiralty Hospital (on the 280th anniversary of the 1st
      Military Naval Clinical Hospital)].

PMID- 8578723
TI  - [The beginnings and development of clinical radiology at the N. N. Burdenko Main
      Military Clinical Hospital].

PMID- 8578724
TI  - [Loyalty to her calling (Ol'ga Parfen'evna Kufareva)].

PMID- 8578725
TI  - [A scientific and practical conference in honor of the 75th anniversary of the
      birth of M. V. Sheliakhovskii].

PMID- 8578726
TI  - [The basic trends in the improvement of qualified and specialized therapeutic
      care in wartime].

PMID- 8578727
TI  - Virally inactivated fresh frozen plasma.
AB  - Several technologies are now available to treat whole fresh-frozen plasma (FFP)
      to inactivate transfusion-transmitted viruses, including pasteurisation,
      solvent/detergent and methylene blue/light. The first two involve creating large
      plasma pools prior to inactivation, while only pasteurisation clearly destroys
      both enveloped and non-enveloped viruses. Some of the issues surrounding the use
      of these products include demonstration of both clinical efficacy and improved
      viral safety, and the need for product licencing. Potential benefits must be
      balanced against the risks of plasma pooling, while the increased costs will
      require comparison with other strategies such as quarantining of plasma. It is
      also recognised that reducing inappropriate FFP usage will play a role in
      improved patient safety.

PMID- 8578728
TI  - Lewis histo-blood group system and associated secretory phenotypes.
AB  - This review summarises present knowledge of the chemistry, immunology, genetics
      and clinical significance of antibodies in the Lewis and secretor histo-blood
      group systems. Although red cell serology has laid the foundations for these
      systems, more recent advances have been made by studying Lewis and related
      glycoconjugates with monoclonal antibodies, determining structures by mass
      spectrometry and NMR spectroscopy, identifying enzymes and their specificities,
      and identifying the genes by molecular biology. The expression of Lewis system
      antigens is dependent on Lewis and secretor loci. Fucosyltransferases coded by
      genes at these loci compete and interact with each other and with other
      transferases to determine an individual's Lewis and secretor phenotype. Exocrine
      epithelial cells, mostly of endodermal origin, synthesise the Lewis antigens
      which, as plasma glycolipids, are secondarily acquired by cells of the peripheral
      circulation. Phenotyping red cells is often regarded as a simple way of
      determining the Lewis and sometimes the secretor status of an individual;
      however, the red cell phenotype is influenced by many factors and may not
      necessarily reflect someone's Lewis and secretor genotypes. Two main red cell
      Lewis groups are usually found, Lewis negative and Lewis positive. In Lewis
      negative individuals, the secretor genotype does not affect the Lewis phenotype,
      but in Lewis-positive individuals, the non-secretor genotype generates the Le(a+b
      ) phenotype, the secretor genotype causes the Le(a-b+) phenotype, and the partial
      secretor genotype gives rise to the Le(a+b+) phenotype.

PMID- 8578729
TI  - Fragmentation of therapeutic human immunoglobulin preparations.
AB  - Some commercial batches of human therapeutic immunoglobulins (Ig) have been found
      to show evidence of molecular fragmentation when examined by molecular sizing
      methodologies including sodium dodecyl sulphate polyacrylamide gel
      electrophoresis [SDS-PAGE] and size exclusion high performance liquid
      chromatography (SE-HPLC). These batches all demonstrated impaired
      immunobiological activity (efficacy) as assessed by Fc function measured using a
      rubella haemolytic assay and as such are likely to be subpotent for therapeutic
      use. Fragmented Igs were characterized by the presence of at least three protein
      bands and peaks additional to monomeric IgG. Incubation of Igs with blood enzymes
      (plasmin and kallikrein) reproduced the fragmentation patterns observed for
      intrinsically degraded batches, suggesting that fragmentation occurred by
      contamination with these proteases from the source material (human blood) during
      manufacture. Intravenous Igs (IVIG) were found to be more susceptible to
      proteolysis than intramuscular Igs, probably as a consequence of the post
      fractionation processing that some IVIGs receive which may induce molecular
      alterations, allowing enzyme access and fragmentation. Two of the products
      examined were found to be relatively resistant to proteolysis and both were
      formulated by processes that limit enzyme activity. These processes were
      inclusion of an enzyme inhibitor, alpha 2-macroglobulin, and formulation at
      acidic pH. Enzyme carry-over into the final product is a likely cause of Ig
      fragmentation, and reduction in levels of such contamination should lead to
      improvements in product stability and efficacy.

PMID- 8578730
TI  - A comparative study of platelets stored in polyvinyl chloride containers
      plasticised with butyryl trihexyl citrate or triethylhexyl trimellitate.
AB  - Platelet concentrates (PCs), stored for 5 days in PL 2209, a new polyvinyl
      chloride (PVC) storage container plasticised with butyryl trihexyl citrate, were
      compared with those stored in PL 1240, a PVC platelet container plasticised with
      triethylhexyl trimellitate. In part 1 of the study, pooled platelet-rich plasma
      (PRP) was aliquoted into each type of pack and pH, pCO2, pO2, hypotonic shock
      response, aggregation responses, lactate, glucose and ATP concentrations, and
      lactate dehydrogenase and beta-thromboglobulin release were compared at days 1, 3
      and 5. In part 2, 12 volunteers gave a unit of blood on two separate occasions
      and PCs produced by the PRP method were stored in PL 2209 or PL 1240 for 5 days
      before autologous reinfusion of a 111In-labelled sample. In vitro results
      demonstrated that PL 2209 was more gas permeable than PL 1240. In part 2 of the
      study, at day 5, pCO2 was 3.13 +/- 0.62 versus 5.14 +/- 0.69 (p < 0.001), whilst
      pO2 was not significantly different for PL 2209 versus PL 1240, respectively. pH
      was better maintained in PL 2209 than in PL 1240 (7.38 +/- 0.13 vs. 7.24 +/-
      0.10, respectively, p < 0.01) after storage for 5 days. These results were
      confirmed by those from part 1. In vivo data were similar for PC stored in the
      two plastics with a multiple-hit recovery of 40.9 +/- 12.1% for PL 2209 and 37.4
      +/- 11.3% for PL 1240, and a multiple-hit survival of 4.89 +/- 1.20 days and 5.28
      +/- 2.06 days for PL 2209 and PL 1240, respectively. gamma-Camera imaging of
      volunteers showed similar biodistribution of radiolabelled platelets stored in
      each container. These results demonstrate that PL 2209 is a suitable container
      for storage of PCs for 5 days.

PMID- 8578731
TI  - Prestorage leukocyte depletion with in-line filtration of whole blood in
      comparison with blood component leukocyte depletion.
AB  - In-line filtration of blood components appears to be an effective method to
      reduce white-cell-induced adverse reactions. We have investigated whether whole
      blood filtration (WBF), prior to component preparation, is comparable with
      filtration of already prepared blood components (CF), i.e. the red cell
      concentrate (RCC) and fresh plasma. Conventionally prepared nonfiltered blood
      components served as a control. No significant differences for most parameters
      investigated were found between leukodepleted RCCs and plasma units prepared by
      CF or WBF. All filtered RCCs and plasma units (CF and WBF) had white blood cell
      contaminations < 1 x 10(5) per unit. Platelets were reduced in all filtered
      components: 95% in plasma and 99% in RCCs. Fresh-frozen plasma (FFP) prepared by
      CF and WBF had normal amounts of factors V, VIII, von Willebrand factor and
      thrombin-antithrombin-III complexes, whereas platelet factor 4 (PF-4) was
      slightly increased in FFP prepared by WBF. RCCs and plasma units prepared from
      filtered whole blood (n = 20) had a significantly greater volume (RCC: 288 +/- 19
      ml; plasma: 274 +/- 20 ml) than conventionally prepared (n = 20) and filtered
      products (RCC: 257 +/- 19 ml, plasma: 259 +/- 19 ml). For early filtration of
      blood components, WBF prior to component preparation seems to offer an
      interesting technique for obtaining a leukocyte-depleted RCC and FFP.

PMID- 8578732
TI  - Human parvovirus B19 infection in blood donors.
AB  - Using an immunodiffusion assay, we tested all of the blood units donated at the
      Fukuoka Red Cross Blood Center from June 1991 to July 1994 for B19 antigen. Over
      this 3-year trial period, we detected 16 viremic cases out of approximately
      560,000 blood donors. Interestingly, most of the viremic donors (15 out of 16)
      were detected between February 1992 and January 1993, which coincided with a
      local erythema infectiosum epidemic in the Fukuoka area (December 1991 to August
      1992). In particular, we detected 4 cases of viremia in March 1992, which was the
      peak of the erythema infectiosum epidemic. The incidence of B19 viremia in this
      peak period was approximately 1/4,000. The viremic donors ranged in age from 17
      to 45 years, and most (11/16) were between 31 and 39 years old. By ELISA, using
      virus particles purified from viremic donor plasma as antigen, we analyzed the
      prevalence of B19-specific antibody among blood donors. The antibody-positive
      rate was approximately 40% in donors 16-30 years old, gradually increased in
      middle age, and reached a peak of 92% in donors more than 61 years old.

PMID- 8578733
TI  - A comparative evaluation of the sensitivity of seven anti-hepatitis C virus
      screening tests.
AB  - The sensitivity of the most recent generation of anti-hepatitis C virus (anti
      HCV) screening tests from seven manufacturers was evaluated with a common panel
      of 530 specimens from 320 HCV-infected subjects. This panel included 221 samples
      from 57 seroconverters (53 pre-sero conversion negative specimens and 168
      positive samples) and 309 selected specimens from 263 other HCV-infected patients
      of which 19% exhibited NS3 or core reactivity alone with the presence of HCV-RNA
      assessed by PCR. None of the seven screening tests detected all infectious and
      antibody-positive specimens. However, important differences were observed between
      these assays in the number of false-negative results, which seemed mainly due to
      nonreactivity of antibody to the NS3 antigen.

PMID- 8578734
TI  - Impact of allergy screening for blood donors: relationship to nonhemolytic
      transfusion reactions.
AB  - There has been some discussion whether the atopic disposition of a blood donor is
      associated with a potentially higher incidence of hypersensitivity nonhemolytic
      transfusion reactions (NHTRs). Serum samples from patients who had suffered from
      NHTRs and samples from the platelet concentrates (PCs) responsible for the
      reactions were examined for total and specific IgE as diagnostic markers for
      allergic events. In addition, the allergy prevalence among 1,088 blood donors was
      determined to analyze the allergy prevalence among our blood donors. Our results
      indicate that in 90% of cases, allergic NHTRs were associated with specific IgE
      antibodies in the recipient's serum, indicating the allergic disposition of the
      patient. In contrast, specific IgE antibodies were detected in only 22% in the
      transfused PCs. However, among all investigated NHTRs, there was not a single
      case in which specific IgE antibodies were detected exclusively in the PC. The
      allergy prevalence among our blood donors was about 26%. In our opinion, the few
      cases in which the allergic disposition of blood donors in combination with the
      allergic disposition of the recipients was associated with NHTRs reflects the
      allergy prevalence among our blood donors in general (26%). On the basis of these
      findings, we conclude that allergy diagnosis for blood donors is only of minor
      value in the prevention and prediction of NHTRs, whereas allergy diagnosis for
      patients who require multiple PC transfusion might be helpful.

PMID- 8578735
TI  - Anti-HLA antibody screening with extracted platelet HLA antigens by the mixed
      passive hemagglutination method.
AB  - For the detection of anti-HLA antibody in the serum of patients receiving
      frequent platelet transfusions, we developed a new method in which platelet
      antigens are extracted into physiological saline containing 3% sucrose and coated
      as a layer on a U-type Terasaki plate. In the present study, screening of anti
      HLA antibodies was conducted with this plate by the mixed passive
      hemagglutination test although the plate contained both HLA and HPA. The
      reactivity determined by this method correlated well with antihuman
      immunoglobulin-lymphocyte cytotoxicity test (AHG-LCT) results (r = 0.963). The
      plate can be preserved for at least 2 years at -80 degrees C and is easier to
      handle than the frozen lymphocyte panels used in the LCT test in which
      lymphocytes must be kept alive. This new method is an alternative way to screen
      HLA antibodies. In addition, it is expected that this method will be used to
      screen anti-HPA antibodies.

PMID- 8578736
TI  - Investigation of the biochemical relationship between the blood group antigens
      Xga and CD99 (12E7 antigen) on red cells.
AB  - The biochemical relationship between the red cell antigens Xga and the MIC2 gene
      product, CD99--previously designated the 12E7 antigen--has been examined by
      immunoblotting and immunoprecipitation analyses of the protein molecules bearing
      these antigens. Immunoblotting of membrane components and Xga-immunoprecipitates
      with anti-Xga has shown that Xga antigen is carried on a broad band of apparent
      molecular weight (Mr)) 24,500-29,500, which consists of a dark stained component
      at M(r)24,500 and a more diffusely stained component at approximately M(r) 26,500
      29,500. Immunoblotting of membrane components and 12E7-immunoprecipitates with
      12E7, and RFB-1 and NaM123 which also recognise CD99, distinguished two bands of
      M(r) 30,000 and 32,000. A non-radioactive immunoprecipitation technique was
      employed, which uses chemiluminescence detection of biotin-labelled red cell
      proteins. The protein of M(r) 32,000, which carries CD99, was identified by this
      method and the red cell quantitative polymorphism of CD99 was demonstrated. When
      the Xga protein was precipitated from biotin-labelled red cells, a protein of
      M(r) 32,000 was coprecipitated. This suggests that the proteins carrying the Xga
      antigen and CD99 are associated in the membrane.

PMID- 8578737
TI  - Identification of two new D variants, DHMi and DHMii using monoclonal anti-D.
AB  - Fifteen examples of red cells are described which showed discrepant reactivity on
      routine grouping with two monoclonal anti-D typing reagents, HAM-A being negative
      and MAD-2 strongly positive. The reaction profile of these cells with a number of
      monoclonal anti-D characterised the samples into two new variant groups, DHMi and
      DHMii. DHMi was characterised by a negative reaction with BRAD-8 and DHMii by a
      negative reaction with BRAD-5. DHMi cells were found to have a papain-sensitive
      site, identified by Mab 21 G6, which was not detectable in DHMii. The presence of
      allo-anti-D in one case of DHMi suggests a partial D in these individuals. The
      positive reaction of HAM-A with sialidase- and endo-F-treated DHMii cells
      suggests that sialic acid and/or N-glycans could possibly be involved in blocking
      the reaction with untreated cells. All samples typed as C-E+. One was e negative
      while the rest had variable depression of the e and f antigens. Marginal
      depression of E was seen with those DHMi cells tested, but not with DHMii cells.
      Data from family studies suggest that the variant D in both DHMi and DHMii is
      inherited as a cDE gene complex and is controlled by the RH locus.

PMID- 8578738
TI  - A rapid and simple ABO genotype screening method using a novel B/O2 versus A/O2
      discriminating nucleotide substitution at the ABO locus.
AB  - An ABO genotype screening method discriminating the common alleles A1, A2, B, O1
      and O2 at the ABO locus was made possible by the discovery of a novel nucleotide
      substitution (G1096A) present only in B and O2 alleles. A rapid and reliable
      single-tube approach using multiplex PCR with four primers amplifying exons 6 and
      7 of the ABO genes followed by simultaneous addition of two restriction enzymes
      was developed and validated in a population of 150 Swedish blood donors. This
      technique is the most cost-efficient and informative ABO genotyping method
      reported to date.

PMID- 8578739
TI  - The beta chain of the GPIIb molecule on ruminant leukocytes and platelets is not
      labelled by the sulfo-NHS-biotin method.
AB  - Glycoprotein (Gp)IIb/IIIa molecules have been immunoprecipitated from platelets
      and leukocytes of cattle, goat, horse, human, sheep and swine using specific
      monoclonal antibodies. The sulfo-NHS-biotin (sulfosuccinimidobiotin) method used
      to label the proteins has been found unsuitable for labelling the beta chain of
      the ruminant GPIIb/IIIa molecule. The beta chain was present on ruminant
      leukocytes and platelets when immunoprecipitates were silver stained.

PMID- 8578741
TI  - Study of HIV antibody screening for blood donors by a pooling-serum method.

PMID- 8578740
TI  - Alloimmunization against Iy, a low-frequency antigen on platelet glycoprotein
      Ib/IX as a cause of severe neonatal alloimmune thrombocytopenic purpura.
AB  - Neonatal alloimmune thrombocytopenia (NAIT) is usually induced by platelet
      specific antibodies against HPA-1a (Zwa) or HPA-5b (Bra). Recently, low-frequency
      alloantigens on the platelet glycoprotein (GP) IIb/IIIa complex have been
      discovered as a cause for NAIT. In this report, a new low-frequency platelet
      specific alloantigen, Iy, is described which induced severe NAIT. The
      corresponding antigen was detected in 1/249 unrelated German blood donors.
      Antibody binding assays with trypsin-digested platelets (ELISA,
      immunoprecipitation with biotin-labelled platelets) indicate that the antigen is
      not localized on the glycocalicin moiety of GP Ib alpha, but may be situated on
      the remnant moiety of GP Ib alpha, GP IX or GPIb beta. Apparently, Iy is not
      related to the HPA-2 (Ko) antigen system.

PMID- 8578742
TI  - Performance of a new third-generation anti-hepatitis C virus ELISA (Monolisa anti
      HCV new antigens) in various serum panels.

PMID- 8578743
TI  - Impact of immunosuppression caused by HIV infection on the replication of
      hepatitis C virus.

PMID- 8578744
TI  - HTLV-I-associated illnesses in Spain. HTLV Spanish Study Group.

PMID- 8578745
TI  - Severe heat treatment of freeze-dried coagulation factor concentrate: is hotter
      necessarily better?

PMID- 8578747
TI  - Do surrogate tests improve the safety of the blood supply?

PMID- 8578746
TI  - Blood group terminology 1995. ISBT Working Party on terminology for red cell
      surface antigens.

PMID- 8578748
TI  - What is the best technique for the detection of red cell alloantibodies?

PMID- 8578749
TI  - [Beta blockers and diuretics: therapeutic drugs of first choice in diabetes
      mellitus and hypertension].
AB  - Patients with diabetes mellitus have a exaggerated risk for cardio- and
      cerebrovascular complications. Hypertension is very common in these patients. To
      date, betablockers and diuretics are the only antihypertensive agents for which a
      reduction of cardio- and cerebrovascular mortality and morbidity in patients with
      or without diabetes mellitus has been proven. Metabolic effects of these
      substances are clinically irrelevant or non existent. Proposed advantages of the
      newer antihypertensive agents, such as reduction of insulin resistance or a
      specific nephroprotective effect of ACE-inhibitors, has not been proven yet in a
      scientific way.

PMID- 8578750
TI  - [Symptomatic bradycardia with amiodarone in patients with pre-existing conduction
      disorders].
AB  - Amiodarone has been shown to improve survival in patients with impaired left
      ventricular function and ventricular trachyarrhythmias. The clinical
      applicability, however, is limited by numerous often serious adverse effects. 70
      patients receiving the treatment with amiodarone for ventricular tacharrhythmias
      were investigated regarding the development of symptomatic bradycardia. Group 1
      consisted of 25 patients with preexisting conduction disorders, 5 had first
      degree heart block, 10 had right bundle branch block, and 7 had left bundle
      branch block on electrocardiographic examination. The 3 remaining patients showed
      asymptomatic sinus node dysfunction defined as sinus arrest or sinuatrial block.
      Amiodarone caused symptomatic bradycardia in 6 of the group 1 patients (II
      degrees-III degrees AV block in 3 patients with preexisting I degree AV block or
      right bundle branch block; intermittent sinus arrest or SA block in the 3 cases
      with previous sinus node dysfunction). 45 patients had no conduction disorders
      before the administration of amiodarone (group II). None of these patients
      developed symptomatic bradycardia. The difference to group I was significant (p <
      0.0005). Thus, patients with preexisting conduction disorders have a substantial
      risk of developing symptomatic bradycardia under amiodarone therapy, with an
      incidence of 24% in group I patients of our collective.

PMID- 8578751
TI  - [Heart surgery in the elderly].
AB  - The number of octogenarian patients undergoing an open heart procedure in our
      unit is the fastest increasing group of patients. Between June 1985 and July 1994
      112 octogenarians (mean age 81.7 years, 60 males, 52 females) underwent cardiac
      operations. The postoperative course was uneventful in 90 patients (80.4%). The
      perioperative mortality rate was 8.9% (10 patients). Mortality was lowest in the
      group receiving aortic valve replacement, with one death out of 30 patients
      (3.3%). The cause of death was left- or biventricular heart failure in more than
      half of the fatalities. Postoperative complications included: AV-block III (n =
      1), postoperative bleeding (n = 2), unstable sternum (n = 3), acute cholecystitis
      (n = 1), low cardiac output syndrome (n = 1), stroke (n = 1), pneumothorax (n =
      2) and urinary tract infections (n = 1). We consider open heart procedures in
      octogenarians, despite a mortality rate of 8.9%, as justified. According to the
      severity and course of clinical symptoms and the type of surgery required,
      selection of patients for operation should be decided on at an early stage of the
      disease. Not only life expectancy increases, but there is also a significant
      increase in life quality for these patients.

PMID- 8578752
TI  - [Comparison of functional findings with results of standardized echography of the
      optic nerve in optic disk drusen].

PMID- 8578753
TI  - [Effect of major epidemics on cultural awareness].
AB  - Mankind has been stricken with "major" epidemic diseases throughout its history.
      The most serious among them immediately threaten man's life e.g. plague, cholera,
      smallpox, typhus, and dysentery, besides, there are others which take a slower
      course e.g. lues, leprosy, leishmaniasis, tuberculosis, and malaria. Yet, the
      "lesser" epidemic diseases like diphtheria, scarlet fever, mumps, pneumococcosis,
      influenza, and most recently AIDS may also turn into "major" ones. Originally,
      man exclusively depended on his genetic makeup for protection, and being
      particularly prone to attacks of disease he was subject to natural selection.
      Thus, only one human species survived, the homo sapiens. Interbreeding achieved
      biologic adaptation and created a balanced genetic polymorphism. Advancing in his
      degree of civilization, man formed groups, developed clothing, fire, houses, and
      tools, and his increasing cultural awareness allowed him to migrate from the
      tropical climates to more temperate, and less disease-infested zones. Immigration
      and wars, and the accompanying infections jeopardized and diminished entire
      populations and eradicated highly developed cultures like that of the American
      Indians. The plague, coming from Asia, and lues, from America, as well as
      cholera, influenza, and smallpox spread around the whole globe. Fear and terror
      led to irrational conclusions and triggered persecutions. The attitude of
      accepting disease as a God-sent fate (Hiob), or a God-sent punishment suppressed
      reasonable measures against disease. The necessary official measures have
      increasingly restricted liberty, and this patronizing treatment needs to be
      opposed with a higher sense of responsibility. Medical art has developed from
      more healing towards prophylactic and predictive medicine, which prognosticates
      the individual susceptibility to particular infections, and other risk factors.

PMID- 8578754
TI  - [Recent molecular and pharmacologic aspects of ACE inhibitors].
AB  - ACE-Inhibitors are well established in the treatment of hypertension and heart
      failure. Other indications, that are under discussion, are coronary artery
      disease, renal failure and diabetes mellitus. The mechanism of action of ACE
      Inhibitors is not only the reduction of angiotensin II and accumulation of
      bradykinin but also an increase of the action potential of the heart muscle,
      increase in glucose uptake in skeletal muscle, inhibition of platelet aggregation
      and opening of the K-ATP-channels.

PMID- 8578755
TI  - [Demonstration of biophysical effects of pulsed laser irradiation with
      histological tissue sections].
AB  - For therapeutic application of laser light it is necessary to minimize defects in
      the nonirradiated tissue. These defects depend on the primary mechanism of
      interaction between tissue and laser light. Three experiments were performed to
      distinguish between mechanical and thermal effects of nano- and microsecond laser
      pulses in skeletal muscle of the rat. The light, transmission and scanning
      electron microscopes were In the ns-experiments the mechanical action of a single
      ns pulse (8 ns) produced a crater. Only zones I and IV developed. With 50 to 100
      pulses all zones can be identified. These results show that a single ns pulse
      suffices to form a tissue crater by mechanical action. A higher number of ns
      pulses leads to heat accumulation and produces thermal lesions similar to those
      seen after application of microseconds-pulses.

PMID- 8578756
TI  - [Incidence of ovarian hyperstimulation syndrome in in-vitro-fertilization
      treatment over a period of 11 years].
AB  - A total of 2915 cycles of controlled ovarian hyperstimulation (COH) were
      performed from 1981 to 1992 in an in-vitro fertilization--embryo transfer (IVFET)
      programme at our institute. In 325 (11.2%) cycles an ovarian hyperstimulation
      syndrome (OHSS) developed. It was defined if more than 10 follicles with a size
      of > 15 mm were found on the day of follicle puncture. OHSS was found to be more
      frequent in the 3rd quarter of the years. Soltriol or melatonin may play a role
      in this context. Additionally, we were able to confirm some risk factors that
      were previously reported to be associated with the OHSS: use of gonadotropin
      releasing hormone agonist (GnRHa) protocols, and young age (< 35 years). The
      pregnancy rate was found to be higher among OHSS cases.

PMID- 8578757
TI  - [Assessment of experimentally-induced pain effects and their elimination by
      hypnosis using pupillometry studies].
AB  - Hypnotherapeutical technique were often used for control of pain. However, an
      objective examination of this phenomenon was seldom carried out. The aim of the
      study was the psychophysiological objectivation of the effect of experimental
      induced pain and the elimination of pain by means of hypnosis. 22 healthy
      volunteers (11 female and 11 male) aged between 22 and 35 years participated in
      the study. In the 1st phase of the experiment static pupillometry was carried out
      before randomized presentation of a light stimulus (143 lux, 0.3 sec) and of a
      pain stimulus (coldness-spray, -50 degrees C, 0.5 sec) respectively. Afterwards
      the dynamic pupillary measurement was done. Additionally the Fourier analyses of
      pupillary oscillations reflecting central nervous activation during the static
      measurement (25,6 sec) was calculated. In the 2nd phase the subjects were
      investigated by means of the same techniques during hypnosis with specific
      suggestions for elimination of pain. Under light condition as well as after
      induction of pain an autonomic deactivation could be observed during hypnosis.
      Furthermore under pain condition a central deactivation could also be found,
      reflecting the depth of the hypnosis and the reduced perception of pain.

PMID- 8578758
TI  - Effects of garlic oil on rat hepatic P4502E1 expression.
AB  - 1. The effects of garlic oil (GO) on the expression of P4502E1, glutathione S
      transferase (GST) and microsomal epoxide hydrolase (mEH) were assessed by
      metabolic activities, immunoblot and RNA blot analyses in the rat. 2. p
      Nitrophenol (PNP) hydroxylase activity decreased in the hepatic microsomes
      isolated from rats treated with GO at 200 mg/kg b.w. by 10-30% as compared with
      control. Pyrazine-inducible P4502E1 expression was decreased by approximately 40%
      following concomitant treatment of animals with GO at the dose of 200 mg/kg from
      day 1 to 3 post-treatment, as evidenced by PNP hydroxylase activity. The rates of
      aniline hydroxylase and NDMA demethylase activities in GO-treated animals were
      consistent with those of PNP hydroxylase activity. Treatment of animals with 500
      mg/kg GO resulted in suppression of P4502E1-mediated catalytic activities, as
      monitored by both PNP and aniline hydroxylase activities, whereas the effects at
      the dose of 1000 mg/kg were identical with those at 500 mg/kg b.w. 3. Immunoblot
      analyses of hepatic microsomes, using an anti-P4502E1 antibody, showed that GO
      minimally suppressed constitutive P4502E1 expression at 24, 48 and 72 h post
      treatment at the daily doses from 200 to 1000 mg/kg b.w., as compared with
      vehicle-treated animals. Time-dependent pyrazine induction of P4502E1, however,
      was substantially blocked by concomitant treatment of animals with 200 mg/kg GO
      to the levels of control. Treatment at the dose of 1000 mg/kg failed to further
      suppress P4502E1 levels. GO treatment caused no changes in the levels of P4502E1
      mRNA, as assessed by slot blot analyses. 4. Cytosol produced from the GO-treated
      rat showed approximately 40% increases in GST conjugating activity toward 1
      chloro-2,4-dinitrobenzene, whereas mEH protein levels were 1.5-2.0-fold greater
      than control with similar increases in the mRNA levels noted. 5. These results
      demonstrate that GO suppresses inducible P4502E1 expression more significantly
      than constitutive expression, and that GO induces GST and mEH expression to a
      certain extent.

PMID- 8578759
TI  - Effect of cyclophosphamide administration on the activity and relative content of
      hepatic P4502D1 in rat.
AB  - 1. The effects of the administration of the anticancer and immunosuppressive
      drug, cyclophosphamide, to the rat on hepatic P4502D1 activity and content in the
      microsomal fraction have been examined. 2. Liver microsomes were obtained from
      male Hooded Wistar rats administered a single dose (i.p.) of saline or
      cyclophosphamide (200 mg/kg). Rats receiving cyclophosphamide were killed 1, 4,
      7, 10 or 14 days after cyclophosphamide administration. The O-demethylation of
      dextromethorphan to dextrorphan was used to monitor 2D1 activity. 3. The mean
      Vmax for dextrorphan formation was reduced significantly (p < 0.0001) 7, 10 and
      14 days after cyclophosphamide administration compared with the control group
      (control, 0.32 +/- 0.07; 7-day, 0.20 +/- 0.08; 10-day, 0.11 +/- 0.02; and 14-day
      group, 0.15 +/- 0.02 nmol/mg/min). 4. Western blotting revealed that there was a
      significant reduction (p < 0.0005) in the microsomal relative 2D1 content 10 days
      after cyclophosphamide administration compared with the control group (control,
      1.25 +/- 0.44; and 10-day group, 0.65 +/- 0.14). 5. The activity of reduced
      nicotinamide adenine dinucleotide phosphate P450 reductase was significantly
      reduced (p < 0.0001) 7, 10 and 14 days following cyclophosphamide administration
      (control, 215 +/- 24; 7-day, 102 +/- 20; 10-day, 59 +/- 4 and 14-day group, 76 +/
      8 nmol/mg/min). Cytochrome b5 content was significantly reduced (p < 0.0001) 7
      and 10 days following cyclophosphamide administration (control, 0.46 +/- 0.13; 7
      day, 0.28 +/- 0.07 and 10-day group, 0.20 +/- 0.03 nmol/mg). 6. The significant
      reductions in the activity of rat hepatic microsomal 2D1 following
      cyclophosphamide administration, as seen by the alterations in mean Vmax for
      dextrorphan formation, do not appear to be due to a single factor, but may result
      from a combination of several events, including reductions in relative 2D1
      content, reduced nicotinamide adenine dinucleotide phosphate P450-reductase
      activity and cytochrome b5 content.

PMID- 8578760
TI  - Species and sex differences of testosterone and nifedipine oxidation in liver
      microsomes of rat, dog and monkey.
AB  - 1. Species and sex differences in testosterone hydroxylation and nifedipine
      oxidation in liver microsomes from rat, dog and monkey have been investigated. 2.
      The formation of 2 alpha-, 2 beta-, 6 beta-, and 16 alpha-hydroxytestosterone and
      androstenedione in the male rat was higher than that in the female rat.
      Microsomes prepared from the male rat oxidized nifedipine about eight times
      faster than did those from the female rat. In contrast, marked sex-related
      differences were not seen in the dog and monkey. 3. Nifedipine oxidase activity
      in rat, dog and monkey correlated significantly with the activities for both
      testosterone 2 beta-hydroxylation and 6 beta-hydroxylation, suggesting the
      involvement of P4503A isozymes in these reactions. The ratios of formation of the
      2 beta- to 6 beta-hydroxytestosterone in male rat and monkey were 0.17 and 0.18
      respectively, whereas that in dog was 0.46. The corresponding activity ratios
      catalysed by P450DPB-1, a P4503A isoform purified from dog liver microsomes, was
      0.36. 4. The formation of 16 beta-hydroxytestosterone was higher than that of the
      16 alpha-hydrolated metabolite in liver microsomes from monkey, whereas 16 alpha
      hydroxytestosterone was the predominant metabolite in the rat and dog, indicating
      species differences in stereoselectivity at the 16-position.

PMID- 8578761
TI  - Cyclophosphamide administered repeatedly to the male rat and as a single dose to
      the female rat. Its effects on hepatic and pulmonary P450 and associated enzymes.
AB  - 1. Two different aspects of the effects of the cytotoxic agent cyclophosphamide
      (CP) on rat P450 and associated enzymes have been examined. 2. First, the effects
      of CP, administered as a single 200 mg/kg dose, on hepatic and pulmonary P450 and
      some associated enzymes in the female rat have been investigated. Second, the
      effects of repeat doses of CP (40 mg/kg on days 0-4 with killing on days 5, 8 and
      11) to the male rat have been examined. 3. CP decreased the activity of the
      female rat hepatic enzymes 2A1, 2C6 and/or 2C12 and 2E1, NADPH-P450
      oxidoreductase and 17 beta-oxidoreductase and the pulmonary enzyme 2B, 7 days
      after its administration. The decreases in the activity of the enzymes 2E1 and
      NADPH-P450 oxidoreductase were accompanied by a corresponding change in the
      amount of enzyme protein indicating that the alteration in expression of these
      enzymes occurred via changes in transcription and/or translation or protein
      degradation. 4. CP also impaired its own activation 7 days after its
      administration to the female rat. 5. The change in female enzyme profile was
      accompanied by a reduction in the hormones oestradiol, T4 and T3 7 days after CP
      administration. 6. Despite an apparent trend for an increase in activity on day
      5, a decrease on day 8 and a subsequent increase on day 11, repeat doses of CP to
      the male rat generally did not alter the P450 isoforms 2A2, 2B1, 2C11, 2E1 and
      3A2 or 17 beta-oxidoreductase, NADPH-P450 oxidoreductase and steroid 5 alpha
      reductase. 7. Chronic administration of CP to the male rat significantly reduced
      erythromycin demethylase and NADPH-P450 oxidoreductase 8 days following
      commencement of dosing and significantly increased 2A2 11 days following
      commencement of dosing. There was also a statistically significant increase in
      pulmonary 2B 5 days following commencement of dosing. 8. Plasma testosterone and
      TSH were unchanged following repeated dosing with CP while T3 was significantly
      decreased on days 5, 8 and 11 and T4 was significantly decreased on day 8.

PMID- 8578762
TI  - Species- and gender-related differences in amine, alcohol and phenol
      sulphoconjugations.
AB  - 1. Species-, gender- and strain-related differences in amine sulphoconjugations
      were studied in 105,000 g supernatants of liver samples isolated from mouse, rat,
      guinea pig, rabbit, dog, monkey and man and were compared with those of alcoholic
      and phenolic compounds. Substrates examined were desipramine (an alkylamine),
      piperazine and piperidine derivatives (alicyclic amines), aniline (an arylamine),
      tiaramide and dehydroepiandrosterone (alcoholic compounds) and 2-naphthol (a
      phenolic compound). 2. Sulphoconjugating activities of alicyclic and aryl-amines
      and tiaramide varied depending on the animal species, sex and strain used. In all
      animal species examined, the activity for desipramine was low or negligible but
      for 2-naphthol was consistently detected and high. Amine sulphoconjugations were
      higher in rabbit than in other animal species. Dog hepatic 105,000g supernatants
      exhibited low or neglible activities for amines and tiaramide. Females showed
      higher sulphoconjugating activities for all substrates in mouse and for amines
      and tiaramide in rat; males exhibited higher activities for 2-naphthol in rat and
      monkey and for amines in rabbit; there were no clear sex-related differences in
      other sulphoconjugations. 3. Among BALB/c, C57BL/6, DBA/2, and AKR mouse strains,
      the AKR strain showed higher activities towards amines and tiaramide than others.
      4. In human liver 105,000g supernatants, sulphoconjugating activities for
      alicyclic amines, dehydroepiandrosterone, and 2-naphthol were detected. Among
      them, higher activities were observed in piperazine and phenol
      sulphoconjugations. There were no sex-related differences in the activities of
      all substrates examined. Good correlations were observed in activities between
      alicyclic amine and dehydroepiandrosterone sulphoconjugations. 5. These results
      indicate that activities of amine and alcohol sulphoconjugations vary
      considerably depending on the substrate, species, sex and strain but phenol
      sulphoconjugation is consistently detected in all species examined.

PMID- 8578763
TI  - Inhibition of p-nitrophenol glucuronidation by calcium mobilizing hormones.
AB  - 1. Vasopressin and phenylephrine markedly inhibited the glucuronidation of p
      nitrophenol in isolated murine hepatocytes. 2. After longer preincubation of
      hepatocytes in the presence of vasopressin or phenylephrine the rate of
      conjugation began to return to the control values indicating the reversibility of
      the inhibition caused by these agents. 3. The inhibitory effect of both agents
      was dependent on the Ca2+ filled state of the intracellular stores. 4. The
      inhibition caused by the alpha 1 receptor agonist phenylephrine was receptor
      mediated because it could be prevented by the addition of alpha 1 antagonist
      prazosin. 5. The data support the theory that the maintenance of the intralumenal
      Ca2+ concentration is necessary for the optimal activity of p-nitrophenol UDP
      glucuronosyl-transferase.

PMID- 8578764
TI  - Fungal transformations of antihistamines: metabolism of brompheniramine,
      chlorpheniramine, and pheniramine to N-oxide and N-demethylated metabolites by
      the fungus Cunninghamella elegans.
AB  - 1. Two strains of the filamentous fungus Cunninghamella elegans (ATCC 9245 and
      ATCC 36112) were screened for their ability to metabolize three alkylamine-type
      antihistamines; brompheniramine, chlorpheniramine and pheniramine. 2. Based on
      the amount of parent drug recovered after 168 h of incubation, C. elegans ATCC
      9245 metabolized 60, 45 and 29% of brompheniramine, chlorpheniramine and
      pheniramine added respectively. The results from strain ATCC 36112 were
      essentially identical to those of strain ATCC 9245. 3. The metabolic products of
      N-oxidation and N-demethylation were isolated by reversed-phase hplc and
      identified by analysing their mass and proton nmr spectra. For all three
      antihistamines, the mono-N-demethylated metabolite was produced in the greatest
      amounts. The chloro- and bromo-substituents appeared not to affect the route of
      metabolism but did influence the relative amounts of metabolites produced. 4.
      Circular dichroism spectra of the metabolites and the unmetabolized parent
      antihistamines showed each to be a racemic mixture of the (+) and (-) optical
      isomers. In addition, comparison of the metabolism of racemic chlorpheniramine to
      that of optically pure (+) chlorpheniramine showed no significant differences in
      the ratios of metabolites produced. There was therefore no metabolic
      stereoselectivity observed by the fungal enzymes.

PMID- 8578765
TI  - Benzene metabolism in rodent hepatocytes: role of sulphate conjugation.
AB  - 1. Hepatocytes isolated from the adult male NMRI mouse or Wistar rat were
      incubated for 1 h with 0.5 mM 14C-benzene, the supernatant was separated from the
      cells, and analysed for benzene metabolites. Separately, formation of sulphate
      conjugates during benzene metabolism was studied in hepatocytes in the presence
      of 35S-sulphate. In addition sulphate conjugation of the benzene metabolites
      hydroquinone and 1,2,4-trihydroxybenzene was investigated in mouse liver cytosol
      supplemented with 3'-phosphoadenosine-5'-phospho-35S-sulphate. 2. Two novel
      metabolites, not detectable in rat hepatocyte incubations, were found in mouse
      hepatocytes, and were identified as 1,2,4-trihydroxybenzene sulphate and
      hydroquinone sulphate. Formation of the 35S-labelled conjugates could be
      demonstrated in incubations of mouse liver cytosol with hydroquinone or 1,2,4
      trihydroxybenzene supplemented with 3'-phosphoadenosine-5'-phospho-35S-sulphate,
      and in mouse hepatocytes incubated with benzene and 35S-sulphate. 3. In
      comparison with hepatocytes from the Wistar rat, hepatocytes from the NMRI mouse
      were almost three times more effective in metabolizing benzene. The higher
      formation of hydroquinone, and the formation of trihydroxybenzene sulphate and
      hydroquinone sulphate, mainly contributed to the higher rate of benzene
      metabolism. 4. In conclusion, qualitative and quantitative differences in benzene
      metabolism may contribute to the higher susceptibility of mouse towards the
      myelotoxic and leucaemogenic action of benzene.

PMID- 8578766
TI  - Anti-peptide antibodies to the P4502D subfamily in rat, dog and man.
AB  - 1. In order to obtain specific antibodies of the P4502D subfamily, we generated
      two anti-peptide antibodies against synthetic peptides, DPAQPPRD (peptide A) and
      DPTQPPRH (peptide B). The sequence of peptide A occurs in rat P4502D2, P4502D4
      and human P4502D6, whereas the sequence of peptide B occurs in the dog P4502D
      subfamily. These sequences are closely related to an epitope of liver/kidney
      microsomal autoimmune hepatitis. 2. In immunoblotting studies, the anti-peptide
      antibody against peptide A recognized a 49-KDa protein in microsomes derived from
      human lymphoblasts expressing P4502D6 and rat liver. It showed no crossreactivity
      with microsomes from dog liver. In contrast, the anti-peptide antibody against
      peptide B recognized a 49-KDa protein only in microsomes of dog liver. These
      indicate that each anti-peptide antibody has the specificity for the respective
      sequences of the members of P4502D subfamily, with the species investigated
      herein. 3. In immunoinhibition studies, the anti-peptide antibodies against
      peptide B inhibited bunitrolol 4-hydroxylation and propranolol 4,5-hydroxylation,
      which are mediated by the dog P4502D subfamily. These data suggest that the anti
      peptide antibodies against peptide B bind to the native and denatured forms of
      the P4502D subfamily. 4. The present study has demonstrated that the anti-peptide
      antibodies against this region are useful for studying the members of the P4502D
      subfamily.

PMID- 8578767
TI  - Changes in the metabolism of three model substrates catalysed by different P450
      isozymes when administered as a cocktail to the carbon tetrachloride-intoxicated
      rat.
AB  - 1. Caffeine (CA) metabolism in animal and man is mainly catalysed by P4501A2.
      Lidocaine (LID) and phenytoin (PHT) are metabolized by P4503A2 and 2B1/2 in
      animals and 3A4 and 2C9 in man, respectively. 2. We investigated the possibility
      of predicting liver damage from changes in blood concentrations after
      simultaneous i.v. administration (cocktail study) of the three probe drugs CA (10
      mg/kg), LID (4 mg/kg) and PHT (4 mg/kg), and their main metabolites, paraxanthine
      (PX), monoethylglycinexylide (MEGX) and 5-(p-hydroxyphenyl)-5-phenylhydantoin (p
      HPPH) respectively. 3. The metabolism of CA, LID and PHT and production of their
      metabolites (PX, MEGX and p-HPPH) in the carbon tetracholride (CCl4 0.25 and 0.5
      ml/kg)-treated rat were reduced in comparison with the control group. 4. The
      ratios (PX/CA and p-HPPH/PHT) of CA and PHT to the serum levels of the their
      metabolites 2 h after i.v. administration of three drugs to the CCl4-treated rat
      were significantly reduced. 5. The correlation coefficients among CLs of CA, LID
      and PHT, and the PX/CA and p-HPPH/PHT ratios in rat pretreated with different
      doses of CCL4 are very high. 6. These results suggest that different estimates of
      hepatic oxidizing capacity, catalysed mainly by P4501A2, 2C and 3A, may be
      related to the extent of liver disease in the CCl4-intoxicated rat. Therefore a
      'cocktail' is not in fact needed to assess hepatic damage in the CCl4-intoxicated
      rat.

PMID- 8578768
TI  - Pharmacokinetics and tolerance of a new fluoroquinolone antimicrobial drug after
      single oral doses in healthy volunteers.
AB  - 1. The pharmacokinetics and tolerance of DV-7751a were investigated in healthy
      male Caucasian volunteers after single oral doses (100, 200, 400 and 800 mg). 2.
      DV-7751a was rapidly absorbed in the fasted state. The mean maximum concentration
      in plasma (Cmax) ranged from 0.27 to 1.98 micrograms/ml for the 100-800-mg dose
      and the mean time to reach Cmax (tmax) ranged from 1.1 to 1.9 h. The terminal
      half-life ranged from 8.75 to 10.0 h. A good linear correlation (r = 0.974) was
      found between doses from 100 to 800 mg and the resulting area under the
      concentration-time curve (AUC). The plasma protein binding of the drug was in the
      range of 57-65%. 3. Within 48 h, the cumulative urinary excretion of unchanged
      drug amounted to 22.0-26.8% of the dose administered. Faecal recovery of the drug
      up to 72 h after the 400-mg dose was about 12% of the dose given. 4. Adverse
      events thought to be possibly related to the drug included headache, rash, leg
      cramp, diarrhoea, abdominal pain, CNS depression and dizziness. DV-7751a,
      however, was well tolerated with no serious adverse events at any doses and all
      subjects completed the study. No drug crystals were observed in the urine.

PMID- 8578769
TI  - Pharmacokinetics of mexiletine enantiomers in healthy human subjects. A study of
      the in vivo serum protein binding, salivary excretion and red blood cell
      distribution of the enantiomers.
AB  - 1. The disposition kinetics of serum free (unbound) and total mexiletine
      enantiomers were studied in 12 healthy subjects following oral administration of
      200 mg racemic mexiletine hydrochloride. The disposition of the enantiomers of
      mexiletine in urine, saliva, and red blood cells was also examined. 2. The mean
      peak serum total mexiletine concentration of 217 +/- 69 ng/ml for R(-)-mexiletine
      was found to be significantly greater than a mean of 197 +/- 56 ng/ml for S(+)
      mexiletine. The mean serum total R(-)-mexiletine concentrations were also found
      to be significantly greater than those for S(+)-mexiletine during the first 6 h
      following drug administration. The oral absorption, as well as the rapid and the
      terminal disposition kinetic parameters between the mexiletine enantiomers, were
      not significantly different. 3. Comparative in vitro serum protein binding of
      mexiletine enantiomers examined by ultrafiltration and equilibrium dialysis
      indicated a pH-dependent stereoselective binding of the enantiomers to serum
      proteins. A serum pH ranging from 6.3 to 9.4 was found to correlate with serum
      protein binding of the enantiomers from approximately 30-80% respectively. Within
      the same serum pH range, the serum free drug R(-)/S(+) ratios were found to
      decrease from 1.0 to 0.7 respectively. At serum pH7.4, a mean serum free fraction
      of 0.57 +/- 0.7 and 0.56 +/- 0.6 were observed for R(-) and S(+)-mexiletine
      respectively. 4. The overall mean saliva/serum-free mexiletine enantiomer area
      under the concentration-time curve ratios of 6.10 +/- 2.82 and 7.49 +/- 3.48 for
      R(-)- and S(+)-mexiletine respectively were found to be significantly different.
      The overall mean saliva R(-)/S(+) enantiomer ratio of 0.89 +/- 0.02 (mean +/- SE)
      over 48 h suggested a stereoselective disposition of the mexiletine enantiomers
      in saliva. 5. The mean mexiletine red blood cells to serum-free drug
      concentration ratios among 11 subjects studied were found to range from 0.6 to
      1.4 for R(-)-mexiletine and from 0.6 to 1.8 for S(+)-mexiletine. The overall mean
      ratios of 0.85 +/- 0.06 and 0.84 +/- 0.08 (mean +/- SE) over 48 h for R(-)- and
      S(+)-mexiletine respectively were both slightly but significantly different from
      unity. This data together with an overall red blood cell mean R(-)/S(+)
      mexiletine concentration ratio of 0.91 +/- 0.13 suggested a non-stereoselective
      and passive diffusion of the enantiomers into red blood cells. 6. The cumulative
      amounts of unchanged R(-)- and S(+)-mexiletine in the urine were found to be
      variable among the 12 subjects with a mean percent urinary recovery of 3.49 +/-
      3.35% for R(-)-mexiletine and 3.68 +/- 3.94% for S(+)-mexiletine.

PMID- 8578770
TI  - Oral kinetics of dexfenfluramine and dexnorfenfluramine in non-human primates.
AB  - 1. Large doses of dexfenfluramine in animals cause a decrease of serotoninergic
      markers but none of the species so far investigated shows sufficient kinetic and
      metabolic similarity with man to be a valid model for safety studies. The plasma
      kinetics of dexfenfluramine and its active metabolite dexnorfenfluramine were
      therefore studied in baboon, rhesus and cynomolgus monkeys given dexfenfluramine
      hydrochloride orally (2 mg/kg) in order to investigate whether any of these
      primates have a biodisposition particularly similar to man. 2. The drug was
      rapidly N-deethylated to dexnorfenfluramine achieving comparatively low mean
      maximum plasma levels (Cmax) of 12-14 ng/ml in all primates, and rapidly
      disappeared thereafter with half-lives (t1/2) ranging from 2 to 3 h in the baboon
      and rhesus monkey to 6 h in the cynomolgus monkey. Its normetabolite reached
      higher mean Cmax (52-97 ng/ml) and the t1/2's were longer, varying from about 11
      h in the rhesus monkey to 22 h in the cynomolgus monkey. The metabolite-to-parent
      drug ratio (14-37), in terms of plasma area under curve (AUC), greatly exceeded
      that in man (< 1), being higher than in all species investigated so far. 3.
      Comparative repeat dose simulation in monkey and man indicated that the dosage in
      primates would need to be increased 10-fold to achieve comparable dexfenfluramine
      steady-state plasma Cmax, producing nor-metabolite levels several times those in
      man, whilst for comparable metabolite Cmax, those of the parent drug would be
      correspondingly too low. 4. In view of the different mechanism of action of
      dexfenfluramine and dexnorfenfluramine within the serotoninergic system none of
      these primates is therefore a suitable model for safety assessment in terms of
      exposure of the active moieties in comparison with man.

PMID- 8578772
TI  - [Tumors as sequelae of smoking].
AB  - Cigarette smoking is the most frequent cause of cancer related death in
      industrial countries. Smokers have a more than doubled risk of dying from cancer
      related disease. Tobacco is the cause of 90% of observed carcinomas in organs or
      tissues such as mouth, throat, esophagus, and lungs, which have direct contact to
      tobacco smoke. In addition, other organs such as the pancreas, bladder, cervix,
      and bone marrow develop malignancies of systemic diseases in smoking more
      frequently than in non-smoking persons. This is explained by the distribution of
      tobacco carcinogens and their metabolites via the bloodstream and a specific
      accumulation of these products in certain organs. There is a clear dose-response
      relationship between tobacco smoke and carcinomas. Side stream smoking is also
      known to cause cancer. It increases the incidence of bronchial carcinoma by a
      factor of 1.3. The fact that 25-30% of all cancer related deaths could have been
      prevented by not smoking, has a large social implications when one considers that
      half of the people dying from tobacco related causes are in working age.

PMID- 8578771
TI  - Drug toxicity mechanisms in human hepatoma HepG2 cells: cyclosporin A and
      tamoxifen.
AB  - 1. Mechanisms of drug toxicity operating in human HepG2 hepatoma cells have been
      assessed using cyclosporin A (CsA) and tamoxifen as examples. 2. Either 150
      microM CsA or 50 microM tamoxifen caused approximately 50% loss of HepG2 cell
      viability. alpha-Tocopherol (32 microM) almost completely prevented cell death
      due to either CsA or tamoxifen. Tamoxifen stimulated malondialdehyde formation.
      The toxicity of CsA but not tamoxifen was increased by the glutathione synthesis
      inhibitor, buthionine-S,R-sulphoximine, and decreased by the glutathione
      precursor, L-cysteine. Thus, while both CsA and tamoxifen toxicities involved
      lipid peroxidation, reduced glutathione (or sulphydryl groups) protected against
      CsA but not tamoxifen. 3. CsA was metabolized to M1 and/or M17 in HepG2 cells.
      The effects of the cytochrome P450 inhibitors, ketoconazole and metyrapone,
      indicated that P450 played a role in the toxicity of CsA but not tamoxifen. The
      effects of superoxide dismutase and cytochrome c indicated that tamoxifen
      toxicity involved superoxide formation. 4. These results show that several
      oxidative mechanisms of drug toxicity operate in HepG2 cells.

PMID- 8578773
TI  - [Smoking and peripheral vascular disorders].
AB  - Smoking is a major risk factor for peripheral arterial occlusive disease (PAOD)
      and plays a crucial role in the pathogenesis of the thrombangiitis obliterans
      (TAO), nicotine and carboxyhemoglobin cause functional disturbances and
      structural damage of the endothelial cells which may initiate arteriosclerosis.
      Additional effects of smoking are hyperfibrinogenemia, lowering of HDL
      cholesterol and increased oxidation of LDL-cholesterol. By these mechanisms,
      smoking influences other primary risk factors for arteriosclerosis. Patients with
      PAOD, who continue to smoke, have a worse clinical prognoses with higher
      amputation and mortality rates than those who quit smoking. The most urgent goal
      in the therapy of PAOD and TAO should be an immediate and complete smoking
      cessation. However most patients continue to smoke despite the knowledge of the
      hazards to their health. An appropriate approach to this addiction may be an
      alternative application of nicotine temporarily (transdermal by patches or
      chewing gum) and behavioral treatment. This combined therapy results in better
      success rates in terms of smoking cessation.

PMID- 8578774
TI  - [Smoking and pregnancy].
AB  - The medical consultation during pregnancy should include information about
      smoking and side-stream smoking. More than half of the fetuses are more or less
      exposed to harmful substances passing the placenta due to smoking of the mother
      or smoking persons in the direct environment. The danger due to side-stream
      smoking have to be considered more during the consultation. It is known that
      toxic substances are concentrated higher in the side-stream smoke than in the
      main-stream smoke. Due to enzyme induction, smokers can metabolize toxic
      substances faster than non-smokers or side-stream smokers. Already before a
      planned pregnancy, it should be pointed out that tobacco smoke contains numerous
      teratogenic substances which double the risk of fetal malformations. A high
      consumption of cigarettes induces an increased risk of abortion. An insufficient
      perfusion of the uterus and the placenta causes an O2-debt with an increased risk
      for malformations such as schistasis or an increased rate of premature birth. The
      increased CO content of the maternal blood reduces the O2 transport capacity
      since CO has an about 200 times greater affinity to hemoglobin than O2. These and
      other topics of the consultation for pregnant women are important in the interest
      of the fetus.

PMID- 8578775
TI  - [Prevention of smoking from the psychological medicine perspective].
AB  - Smoking is a complex socio-psycho-biological behavior with high prevalence and
      high risk for several diseases. Referring to a widely accepted concept of
      prevention, the review presents recent psychological and pharmacological
      strategies to cease smoking with respect to theory, application, and evaluation.
      Primary prevention, which includes appropriate settings in schools, families, and
      social groups, seems adequate in preventing people from health problems
      associated with tobacco-smoke. Although evaluations are rarely found, curricula
      starting at childhood and intensive training programs for adolescents can be
      presently recommended. These programs have to take into account specific group
      characteristics and should focus on active and self-controlled behavior without
      smoking. Additionally, negative short-term effects of smoking should be
      emphasized more clearly instead of longterm risks of smoking. The broad diversity
      of secondary prevention programs for smoking cessation and relapse prevention
      includes well established and efficient psychological and pharmacological
      treatments. Flexible combinations of psychotherapeutic and pharmacological
      strategies (e.g. behavioral skill training programs and nicotine replacement
      therapy), which also consider the strength of nicotine dependence and withdrawal
      symptoms, are most promising. For smokers, who continue to smoke despite of
      health damages (e.g. cardiovascular diseases, cancer), intensive
      psychotherapeutic regimens (tertiary prevention) are suggested. However,
      evaluation on this issue is almost missing. In summary, smoking prevention
      programs can be considered to be cost-effective. Nevertheless, 1 year abstinence
      rates range only between 20-30%. Furthermore, there is a strong need for
      psychobiological research on the development of smoking behavior, on long-term
      follow-up of prevention programs, and on outcome prediction.

PMID- 8578776
TI  - [Patient counseling by the physician in smoking cessation--conditions and
      prerequisites].
AB  - The importance of the medical profession for the health consultation, which has
      been more and more emphasized country-wide but also internationally, has only be
      reflected regarding possible positive results rather than real circumstances and
      conditions for realization. This report brings out why the realization of the
      quite reasonable postulate of a medical involvement in the health consultation
      for a tobacco withdrawal is hindered especially from requirements on the level of
      attitude, competence and action which urge to a realistic view of the limits and
      feasibility of the medical involvement.

PMID- 8578778
TI  - [Smoking cessation with the nicotine patch].
AB  - Smoking cessation programs have become much more effective since the transdermal
      nicotine delivery system is available. Nicotine patches are well tolerated, have
      little side-effect and reduce the withdrawal symptoms of nicotine abstinence.
      Short- and long-term abstinence rates increase when nicotine patches are combined
      with behavioral therapy. This paper reports current scientific literature on
      placebo-controlled trials and gives treatment advices for smoking cessation using
      nicotine patches by general practitioners. Although nicotine patches are now
      available in Germany without prescription, therapeutic support by physicians,
      pharmacists or psychologists is indispensable for successful smoking cessation.

PMID- 8578777
TI  - [Non-smoking policy in the hospital: insight into policy-relevant social
      research].
AB  - This article reports on long-term activities of the social research group SALSS
      which have been supported by the Federal German Health Education Authority. Work
      started in 1989/90 with a representative survey among hospital managers in West
      Germany which--soon after reunification--was completed by similar action in East
      Germany. In both cases, the subjects were regulations and actual situation of non
      smokers' protection in hospitals as well as plans for improvement. Based on the
      data gathered, handy information material and campaign aids were developed for
      "frontline" activists. Professional support has been given to persons engaged in
      devising and implementing measures to improve the situation. This includes
      assisting concerned hospitals in patient and staff surveys (design and data
      processing) which are meant to detect the weak spots of non-smokers' protection
      as well as the demands for changes. This contribution contains the findings of
      patient and staff surveys conducted in four establishments which may be regarded
      as typical of German hospitals. There is clear evidence that the rate of smokers
      is higher among staff members than among patients, and that conflicts about
      smoking are most likely to occur within the group of hospital employees.
      Especially non-smoking staff members demand that the hospital management shows
      more commitment to smoking restrictions. The findings support the notion that
      only a broad, careful step-by-step approach has reasonable chances to reduce
      smoking and improve non-smokers' protection in hospitals by combining structural
      measures (better separating smokers from non-smokers) with optimized regulations
      and health education.

PMID- 8578779
TI  - [Smoking cessation with alternative methods].
AB  - Almost every former smoker has ceased smoking by himself. Everybody has collected
      his own experience with it and tried different methods to avoid withdrawal
      symptoms and the urge to start smoking again. During the last decades, many
      different methods for the therapy of smoking cessation have been applied. These
      techniques were often developed with the help of individual experiences. Many
      times, there is a lack of a scientific ground and verifiable investigations for
      these activities. The most important parameter for the smoking cessation is the
      clear and strong intention to quit. This intention may be supported by different
      methods. The mental requirements are discussed and the numerous methods and drugs
      available to quit smoking are described.

PMID- 8578780
TI  - [Prevention, standards and future developments in medical specialties-
      epidemiology].

PMID- 8578781
TI  - [From general practice of an expert assessment service: heavy smoker died of
      acute heart failure in abscessed lobar pneumonia].

PMID- 8578782
TI  - [Free from tobacco. Counseling of smokers in medical practice--experiences from
      the Swiss campaign].
AB  - Physicians can help patients quit smoking by offering advice and counselling.
      Towards this end, the Swiss Medical Association (FMH) together with the Federal
      Office of Public Health developed a programme aimed at improving physicians'
      counselling skills. The programme offers a systematic approach to patient
      counselling. Between 1990 and 1993, on three consecutive occasions Swiss doctors
      (12,000) were mailed an invitation to join the campaign and order their free
      copies of the counselling package. An optional 3 hours training session on how to
      make effect use of the package was also offered. Course participants were
      routinely questioned (pre and post course, and six months after completing the
      course), about their knowledge, attitude and behaviour towards smoking and
      counselling. In 1991 an evaluation of the overall programme was conducted. A
      representative sample of 450 physicians was used for the survey. It was divided
      into 3 groups with 150 physicians each. Group I included those, who both had
      ordered the package and attended the training, group II had the package only,
      while group III had neither. The overall response rate was 80%: For groups I and
      II it was 93% and for the control group it was 76%. 92% of respondents reported
      having heard of the campaign. 51% stated having used one or more of the materials
      included in the package in their daily work. 63% reported an increased frequency
      of intervention activity and 55% stated that their counselling had been more
      successful. Relevant statements amongst the control-group were significantly
      lower -26% with regard to success and 38% with respect to increased frequency of
      interventions (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8578783
TI  - [Report of the 9th World Conference on Tobacco and Health 10-14 October 1994 in
      Paris. Physicians and scientists promote political intervention: smoking is the
      greatest risk to health].

PMID- 8578784
TI  - [Incidence of intervention-related heart valve lesions after high-frequency
      catheter ablation of the left-side accessory atrioventricular conduction
      pathways].
AB  - The aim of this study was to evaluate the incidence of valve lesions after
      radiofrequency catheter ablation of accessory atrioventricular pathways using the
      retrograde transaortic approach. Patients who presented no preexisting detectable
      valve lesion prior to catheter ablation and who underwent a comparable
      echocardiographic examination prior to and after catheter ablation were included
      for data analysis. From January 1991 until May 1993, 113 patients underwent
      radiofrequency catheter ablation of a left-sided accessory atrioventricular
      pathways at our institution. Fifty-nine patients were included in this study.
      Five patients (8.4%) developed new valve lesions after radiofrequency catheter
      ablation. There were two cases (3.3%) of aortic regurgitation and four cases
      (6.7%) of mitral regurgitation. In the majority of cases only mild valve
      regurgitation was detected. A hemodynamically significant valve lesion was
      observed in a single patient (1.6%). We speculate that the new onset of valve
      lesions is mostly due to catheter manipulations rather than due to tissue injury
      related to radiofrequency current application. Echocardiographic examinations
      prior to and after radiofrequency catheter ablation of accessory pathways may
      contribute to a further reduction in intervention-related complications.

PMID- 8578785
TI  - [Improvement of perioperative hemodynamics and gas exchange by inhalation of
      nitric oxide in children with congenital cardiopulmonary defects].
AB  - OBJECTIVES: In critically ill infants and children before or after surgery for
      congenital cardiopulmonary disease it was evaluated whether continuous NO
      inhalation can reduce pulmonary artery pressure (PAP) and improve arterial oxygen
      saturation (SaO2). METHODS: All patients (n = 24; age 1 day-6.5 years) were
      intubated and artificially ventilated. They had either secondary pulmonary
      hypertension (n = 16), acute respiratory distress syndrome (n = 3), or reduced
      SaO2 (n = 5) due to pulmonary hypoperfusion. NO was introduced into the afferent
      limb of the ventilator circuit close to the endotracheal tube, while continuously
      measuring the inspired NO and O2 concentrations. The initially applied
      concentration of NO was 20 +/- 2.0 ppm. RESULTS: The hemodynamic condition and/or
      oxygen saturation was significantly improved by NO in 23 patients (95%). Mean PAP
      declined significantly from 45 +/- 7 to 28 +/- 3.7 mm Hg, while mean systemic
      arterial pressure remained constant (56 +/- 2.1 vs. 58 +/- 2.5 mm Hg). This was
      related to a selective reduction in pulmonary vascular resistance by 48 +/- 8.5%.
      SaO2 increased significantly (p < 0.05) from 83 +/- 2.5% to 93 +/- 1.5% due to a
      decreased intrapulmonary right-to-left shunt. NO therapy was applied with a
      median of 6 days (range 1.5-36 days). During NO inhalation methemoglobin
      concentration was significantly increased (0.77 +/- 0.05% vs. 1.46 +/- 0.15%),
      but neither was oxygen transport capacity affected, nor was any evidence for
      accumulation observed. Using a model ventilatory circuit, a nitric dioxide (NO2)
      formation of 1.14 +/- 0.11% of the applied NO concentration was measured, i.e.
      approximately 0.5 ppm NO2 at 40 ppm NO. This amount of NO2 in the inspired gas is
      well below toxicologically relevant concentrations. CONCLUSIONS: Low-dose NO
      inhalation selectively reduces PAP and improves SaO2 in children with congenital
      cardiopulmonary disease during perioperative intensive care. It is expected that
      the overall hemodynamic improvement is related to a reduced afterload of the
      subpulmonary ventricle without changes in coronary perfusion pressure, as is
      often observed with other vasodilators applied intravenously. We recommend an
      upper dose limit of 40 ppm NO for continuous NO inhalation to avoid possible
      toxicologically relevant NO2 concentrations.

PMID- 8578786
TI  - [Recommendations for prevention of thromboembolism in heart valve diseases.
      Working Group on Valvular Heart Disease, European Society of Cardiology].
AB  - Thromboembolic events are still a major cause of morbidity and mortality in
      patients with native valvular heart disease and in patients with prosthetic heart
      valves. Although the introduction of oral anticoagulation reduced this risk,
      thromboembolism and anticoagulation-related hemorrhages still represent
      significant problems in the management of these patients. In this article the
      guidelines developed by the Working Group on Valvular Heart Disease of the
      European Society of Cardiology for the management of antithrombotic therapy in
      heart valve disease are thoroughly discussed. The indication for and intensity of
      anticoagulation in various clinical situations, the concept of risk factor
      adjusted intensity of anticoagulation, and the concept of control of oral
      anticoagulation with the International Normalized Ratio are presented.

PMID- 8578787
TI  - [Takayasu arteritis--a rare differential diagnosis in aortic dissection. A case
      report].
AB  - A 36-year-old woman was delivered to our hospital with suspected aortic
      dissection from an outlying hospital in May 1994. She reported a history of acute
      and persistent thoracic and epigastric pain. The physical examination revealed a
      minor senso-motorical palsy of the left side as residuum after minor strokes
      occurring 12/93 and 4/94. Also, a marked hypertension (170/100 mm Hg) was
      present. The hematologic and blood chemical values were normal with a white cell
      count of 12,000, an erythrocyte sedimentation rate (ESR) of 19 mm/h and a c
      reactive protein (CRP) of 2.2 mg/dl. The electrocardiogram was normal.
      Transthoracic- and transesophageal-echocardiography (TTE, TEE) revealed an
      eccentric thickening of the whole wall of the descending aorta up to the
      bifurcation with a stenosis at the side of the diaphragma. Those findings were
      confirmed by computed tomography. Because of the acute onset of symptoms and the
      results of the imaging procedures aortic dissection de Bakey type III was
      diagnosed and the patient was treated with beta-blockers. Symptoms were relieved
      over the following days. After 2 days a pleuric effusion developed and all
      inflammatory tests rose (fibrinogen 780 mg/dl, ESR 80 mm/hr, CRP 16 mg/dl). At
      this time the differential diagnosis of an arteritis was considered. A new TEE
      study demonstrated no change, but now more attention was given to the fact that
      no dissection membrane could be visualized and all wall structures were
      thickened. In combination with the history of cerebral infarction due to carotid
      obstruction and the elevated laboratory values the diagnosis of Takayasu-aortitis
      was established and corticoid therapy was started. Within a few weeks the
      arterial changes diminshed markedly and the woman became free of symptoms. This
      case demonstrates the rare situation of an arteritis mimicking aortic dissection,
      in which the clinical course revealed the true diagnosis.

PMID- 8578788
TI  - [A 63-year-old man with uncorrected tetralogy of Fallot].
AB  - An exceptional case of tetralogy of Fallot is reported; the patient survived
      without severe symptoms or surgical treatment. The diagnosis was made by
      echocardiography at the age of 61 years when the patient experienced hypertensive
      retinopathy. Death occurred at 63 from myocardial infarction. It is thought that
      longstanding hypertension had contributed to a diminished right-to-left shunting,
      thus reducing cyanosis and hypoxic damage to the myocardium, which enabled
      prolonged survival.

PMID- 8578789
TI  - [Response to the letter by K. Schror on: Prevention of reinfarction with 100 mg
      or 30 mg ASS daily].

PMID- 8578790
TI  - [Response to the editorial by J. C. Frolich: Aspirin--yes, but 30 mg??].

PMID- 8578791
TI  - [Comment on the contribution by Dr. P. Stahr et al. on the topic "Experimental
      ultrasound angioplasty: in vitro dissolution of thrombi"].

PMID- 8578792
TI  - [Discovery of the pacemaker and heart conduction system in mammals. Fantasy and
      truth].
AB  - The first report about experimental investigations on the origin of the rhythms
      in the mammalian heart were published in 1888 by McWilliam. Similar experiments
      were described by Hering in several publications starting from 1900. The results
      led to the hypothesis of the myogenic genesis of the rhythms. However, in 1907,
      Hering stated that the origin of the stimulus in the mammal heart was probably a
      nervous function. In 1898, 1903, and 1906 Wenckebach described the function and
      the functional localization of the pacemaker in the heart of the intact man, and
      in 1906, he described the morphology of the pacemaker and its blood supply in the
      post mortem human heart. In the same year, Adam analyzed the localization of the
      "natural" pacemaker and the regions of the secondary pacemakers in the mammal
      heart. In 1907, Keith and Flack introduced the term "sino-auricular node". They
      quoted the findings of Wenckebach and Hering, and they mentioned McWilliam. A
      muscular connection between the right atrium and both ventricles of the mammal
      heart was found by Kent and by His in 1893. In 1907, Tawara called the structure
      of the origin of the a-v connection "atrio-ventricular node". It was, however,
      the scientific discovery of Tawara that the a-v pathway was connected with the
      muscles of the ventricles by the Purkinje fibers. He discovered that the pathway
      consists of muscles which are histologically divided and functionally different
      from the other heart muscles. It is a system of specialized muscles which conduct
      the stimulus for the contraction without contracting themselves.

PMID- 8578793
TI  - [Low pacing thresholds of ventricular pacemaker leads: not a marker for large R
      wave amplitudes and high impedance values].
AB  - An optimal position of a ventricular pacing lead in the bottom or apex of the
      right ventricle is defined by low pacing thresholds and high R wave amplitudes.
      At similar pacing thresholds high pacing impedance additionally reduces the
      pacing current delivered by the pacemaker. Finding an optimal position for the
      pacing lead would be facilitated if locations with low pacing thresholds are
      usually associated with great R wave amplitudes and high pacing impedance. This
      study assessed the relationship between ventricular pacing thresholds, R wave
      amplitude, and pacing impedance for present-day pacing leads at implantation. For
      this purpose the acute lead performance of the unipolar lined lead "CapSure SP
      4023" (Medtronic) was studied in 194 patients. PSA 5311 (Medtronic) was used to
      measure pacing thresholds at 0.5 ms in steps of 0.1 V and impedance at 5.0 V/0.5
      ms and to register filtered R wave amplitude. Pacing thresholds were 0.4 +/- 0.2
      V (range 0.1-1.2 V) and impedance 576 +/- 161 ohms (range 262-1200 ohms). An
      intrinsic rhythm was observed in 150 patients with an R wave amplitude of 13 +/-
      5 mV (range 3-28 mV). There was no statistically significant correlation between
      pacing threshold and R wave amplitude (r = -0.09). In respect to impedance,
      neither the correlation with pacing threshold (r = 0.07) nor that with R wave
      amplitude (r = 0.18) was statistically significant. In conclusion, most patients
      had pacing thresholds < 0.5 V at 0.5 ms pulse duration and R wave amplitudes > 10
      mV; fewer than 5% of the patients had pacing thresholds > 0.6 V or R wave
      amplitudes < 5 mV. Lead locations with low pacing thresholds are usually not
      associated with great R wave amplitudes or high impedance.

PMID- 8578794
TI  - [Junctional arrhythmias in radiofrequency modification of the atrioventricular
      node].
AB  - Accelerated junctional rhythm (JR) is known as a response of the atrioventricular
      node to thermal injury and a common finding in radiofrequency ablation for AV
      node reentrant tachycardia. We studied JR during 1314 radiofrequency current
      deliveries in 172 patients with AV node reentrant tachycardia or paroxysmal
      atrial fibrillation in relation to the ablation result. JR in a successful RF
      delivery were characterized by cycle length and conduction. RESULTS: Selective
      slow pathway ablation was performed in 100 patients (Group A), selective fast
      pathway ablation in 41 patients (Group B), and total AV junction ablation in 31
      patients (Group C). A successful radio-frequency ablation without JR was rare
      (sensitivity: 98.8%; specificity: 51.2%). JR during slow pathway ablation had a
      longer cycle length (X +/- SD; CL: 494 +/- 138 ms) and a lower cycle length
      dispersion (delta CL: 178 +/- 199 ms) than JR during fast pathway ablation (CL:
      399 +/- 108 ms; delta CL: 345 +/- 145 ms) or before total AV block (CL: 439 +/-
      163 ms; delta CL: 338 +/- 195 ms). JR with bundle branch block aberration or
      ventriculoatrial block were more often found in group B and group C than in group
      A (BBB: 29% vs. 23% vs. 12%; VA-Block: 80% vs. 82% vs. 33%). Group B and group C
      did not differ significantly. CONCLUSION: JR leading to fast pathway ablation or
      heralding total AV block are characterized by a short cycle length, wide cycle
      length dispersion, and predominantly present ventriculoatrial block. Thus, JR is
      a useful marker to prevent inadvertent AV block in slow pathway ablation.

PMID- 8578795
TI  - [Minimal interval length for safe determination of brief heart rate variability].
AB  - After heart rate variability (HRV) had been established in the clinic, the
      question about the minimum interval length for analyzing electrocardiograms
      emerged. Respiration rate, heart rate and heart rate variability were analyzed in
      25 sport divers during 6 min intervals at control, immersion, submersion and
      while SCUBA diving. Thereafter, the interval length was systematically shortened
      to 1 min. RESULTS: Respiration rate was significantly reduced during submersion
      and diving. Heart rate, in turn, remained essentially unchanged during the four
      experimental steps. The HRV measures in the time domain (standard deviation,
      coefficient of variation, RMSSD and pNN50) exhibited significant changes during
      immersion, submersion and diving compared to control conditions. The spectral
      density in the low frequency range was increased compared to control, the
      increase being significant during diving. Immersion, submersion and diving, thus,
      present strong stimuli for the autonomic nervous system. The length of the HRV
      measures of the time domain could be shortened to 3 min without significant loss
      of information, except for pNN50. Reduction of the respiration rate during diving
      considerably shifted the respiratory arrhythmia from the high to the low
      frequency range. Such shifts deserve special attention interpreting HRV measures
      from the frequency domain. The interval length for the measures in the frequency
      domain could only be shortened to 5 min. CONCLUSION: Measures from the time
      domain, in particular standard deviation and co-efficient of variation, seem to
      be superior to measures from the frequency domain in analyzing short-term HRV.

PMID- 8578797
TI  - Adenovirus vectors as recombinant viral vaccines.
AB  - Adenoviruses can efficiently induce immunity in the lung following single enteric
      delivery. These viruses can also be engineered to express a number of
      heterologous proteins in vitro. In the past 10 years, recombinant adenoviruses
      expressing a variety of antigens have been constructed and tested. This article
      reviews the main properties of adenoviruses which render them attractive for
      vaccine development, as well as the results of the immunization studies performed
      to date. Some disadvantages of this technology and the desired characteristics of
      second generation adenoviral vectors are discussed.

PMID- 8578796
TI  - [Catheter ablation in sinus node tachycardia].
AB  - Sinus node tachycardia is an uncommon cause of paroxysmal supraventricular
      tachycardia. Of those patients who were referred to our clinic for
      electrophysiologic evaluation and catheter ablation, four patients (1 male, 3
      female) were found to have sinus node tachycardia. The diagnosis of sinus node
      tachycardia required all of the following: The P-wave during sinus rhythm had to
      be similar to the P-wave during the tachycardia, the atrial activation sequence
      during sinus rhythm and tachycardia had to be similar, the origin of the
      tachycardia had to be in the high right atrium. In one patient the tachycardia
      was incessant. The other three patients had paroxysmal sinus node tachycardia
      that could be induced by programmed atrial stimulation. No patient had overt
      cardiac disease. One patient had an inducible av nodal reentrant tachycardia and
      one patient had a second atrial tachycardia originating from the basal right
      atrium. Activation mapping during tachycardia was performed in all patients.
      Local atrial activation at the site of successful ablation preceded the P-wave in
      the surface electrocardiogram by 54 +/- 43 ms. In three patients the interval
      from the local atrial activation at the site of successful catheter ablation to
      the onset of the signal from the high right atrium (HRA) ranged from 25 ms to 125
      ms, in one patient the signal from the high right atrium was the earliest
      recorded signal during tachycardia. In all patients the tachycardia was
      terminated with the application of radiofrequency current. Two to a maximum of 12
      radiofrequency current applications were necessary; complications were not
      observed. In all patients a second electrophysiologic study was performed 8 +/- 2
      weeks after successful catheter ablation; no patient had inducible sinus node or
      atrial tachycardia. During a follow-up of 5 +/- 2 months, no patient had a
      recurrence of sinus node tachycardia or required antiarrhythmic medication. It is
      concluded that catheter ablation in patients with sinus node tachycardia is an
      effective and safe treatment.

PMID- 8578799
TI  - Mapping of two overlapping linear epitopes in Pfg27 recognized by Plasmodium
      falciparum transmission-blocking monoclonal antibodies.
AB  - We have reported previously the production of Plasmodium falciparum transmission
      blocking monoclonal antibodies (mAb) recognizing a reduction-insensitive cross
      reacting epitope in the gametocyte antigen Pfg27 and the gamete surface antigens
      Pfs230 and Pfs48/45. In this study, the amino acid sequence of this epitope in
      Pfg27 was determined. First, the epitope was localized near the N terminus of the
      protein by probing recombinant overlapping fragments spanning Pfg27 with
      transmission-blocking mAb in immunoblot experiments. The amino acid sequence of
      the epitope was then determined by using overlapping synthetic peptides spanning
      the smallest immunoreactive recombinant fragment in an ELISA. The sequence
      KPLDKFGNIYDYHYEH (amino acids 10-25 in the Pfg27 sequence) was shown to contain
      two overlapping epitopes recognized by transmission-blocking mAb. Comparison of
      the sequence of the gene encoding Pfg27 in seven different P. falciparum strains
      demonstrated that these sequential epitopes are totally conserved. Immunization
      of mice with synthetic peptides derived from Pfg27, conjugated with keyhole
      limpet hemocyanin (KLH) and formulated in Freund's adjuvant or alum, resulted in
      the production of antibodies capable of recognizing the peptides as well as the
      native Pfg27.

PMID- 8578798
TI  - Theileria annulata sporozoite antigen fused to hepatitis B core antigen used in a
      vaccination trial.
AB  - A C terminal fragment (SR1) of SPAG-1, a sporozoite surface antigen of Theileria
      annulata, has been expressed as a fusion protein in the e1 loop of hepatitis B
      core antigen (HBcAg). This recombinant antigen (HBcAg-SR1) is produced in the
      form of self-assembling polyhedral particles which have been visualised under the
      electron microscope. Cattle immunised with HBcAg-SR1 produced high titres of
      neutralising antibodies. A significant T cell response to both the HBcAg and SR1
      determinants was observed but evidence of a T suppressor determinant in SR1 was
      also revealed. Immunised cattle showed some evidence of protection to sporozoite
      challenge as assessed by severity of the disease. The significance of these
      findings for the development of a sub-unit vaccine against T. annulata is
      discussed.

PMID- 8578800
TI  - Recombinant gp160 vaccination schedule and MHC HLA type as factors influencing
      cellular responses to HIV-1 envelope glycoprotein. NIAID AIDS Vaccine Clinical
      Trials Network.
AB  - This study assessed (1) T-cell responses following vaccination of HIV-1 negative
      volunteers with HIV-1LAI recombinant gp160 (rgp160) vaccine, and (2) effects of
      vaccine injection schedule and MHC HLA type on those responses. In one trial,
      volunteers received rgp160 in two accelerated schedules (Groups 1 and 2). In the
      other trial, volunteers received rgp160 vaccine at 0, 1, 6, and 12 months and
      some received vaccine at 18 months (Groups 3 and 4). Peripheral blood mononuclear
      cells (PBMC) from vaccinees in Groups 3 and 4 were stimulated by more peptides
      representing envelope glycoprotein T-cell epitopes than Groups 1 and 2 (p =
      0.01). Transient anti-envelope glycoprotein CTL activity was more frequently
      detectable in Groups 1 and 2 (p = 0.03). MHC HLA-Cw7, DR1 and DQw1 alleles
      appeared to be associated with PBMC responses to envelope glycoprotein.

PMID- 8578801
TI  - The effect of temperature on the stability of the synthetic SPf(66)n malaria
      vaccine.
AB  - We hereby report on the effect of temperature on the physico-chemical and
      immunogenic characteristics and stability of the SPf(66)n synthetic malaria
      vaccine. The pattern of polymerization, the adsorption to aluminium hydroxide and
      the immunological properties of these vaccine groups were not significantly
      affected.

PMID- 8578802
TI  - Antibody responses and reactions to the whole cell pertussis component of a
      combined diphtheria/tetanus/pertussis vaccine given at school entry.
AB  - To measure the clinical effect of adding a whole cell pertussis component to
      diphtheria/tetanus vaccine (DT) given as a pre-school booster, 190 children aged
      4-5 years were randomised by a double-blind method to receive either
      diphtheria/tetanus/pertussis (DTP) or DT vaccine in a 1:1 ratio at selected
      clinics in England. The geometric mean antibody titres to each of the three
      pertussis antigens were at least sixfold higher in the DTP than the DT vaccine
      group and equalled or exceeded those in infants immediately after primary
      immunisation with DTP vaccine. There were no significant differences between DTP
      and DT vaccinated children in their diphtheria and tetanus antitoxin levels. The
      frequency of large local reactions and systemic symptoms such as crying and a
      disturbed night was 2-3-fold higher in the DTP vaccinees than in the DT
      vaccinees. Medication was given to 44% of DTP and 23% of DT vaccinees (p =
      0.006). Although the change to whole cell DTP vaccine at school entry would
      result in good pertussis antibody titres, the 2-3-fold increase in reactogenicity
      that would be caused may be unacceptable at a time when whooping cough is not
      circulating widely. Evaluation of acellular DTP vaccines given as a pre-school
      booster in children vaccinated under the accelerated schedule is planned.

PMID- 8578803
TI  - Antigenicity and immunogenicity of recombinant envelope glycoproteins of
      SIVmac32H with different in vivo passage histories.
AB  - Shortly after infection of two rhesus monkeys (Macaca mulatta) either with a
      SIVmac32H challenge stock or with the same virus that had been passaged in
      another rhesus monkey for 11 months, SIV-envelope genes were cloned from their
      peripheral blood mononuclear cells and subsequently expressed by recombinant
      vaccinia viruses. The molecular weights and antigenicities of the thus produced
      envelope glycoproteins were largely identical to those of the native SIV. The
      envelope glycoprotein derived from the in vivo passaged virus proved to be poorly
      recognized by virus neutralizing monoclonal antibodies directed against one of
      the seven antigenic sites for which monoclonal antibodies were available.
      Immunization studies in rats showed that this protein was also less efficient in
      inducing antibodies against this antigenic site, and that it induced
      significantly lower levels of virus neutralizing antibodies than the other SIV
      envelope glycoprotein. The immunogenicity of the SIV-envelope glycoprotein
      incorporated into immune stimulating complexes (iscoms) was compared to that of
      the same protein presented with Quil A or MDP-tsl.

PMID- 8578804
TI  - The use of synthetic peptides can be a misleading approach to generate vaccines
      against scorpion toxins.
AB  - Seven peptides corresponding to the amino acid sequence of toxin 2 from the
      scorpion Centruroides noxius were chemically synthesized, purified and assayed in
      mice for their putative neutralizing properties against scorpion toxins. All the
      peptides were immunogenic and some produced neutralizing antibodies, as verified
      by injecting the antisera with toxin into naive animals. However, direct
      challenge of pre-immunized mice (with the longest synthetic peptides of 27 and 57
      amino acid residues) revealed an unexpected sensitization phenomena: the animals
      did not resist injection of one LD50 of purified toxin 2 (5% survival), but pre
      immunization of mice with native toxin protected 100% of the animals. These
      findings suggest that vaccine preparations with synthetic peptides corresponding
      to the amino acid sequence of certain toxins should be analyzed cautiously.

PMID- 8578805
TI  - Human antibody response to meningococcal transferrin binding proteins: evidence
      for vaccine potential.
AB  - During iron-limited growth Neisseria meningitidis expresses two transferrin
      binding proteins, TBP1 and TBP2, with molecular masses of approximately 98 and 65
      90 kDa depending on strain. Mixtures of TBP1 and TBP2 (TBP1 + 2) from three
      meningococcal strains were purified using affinity chromatography and used to
      determine anti-TBP antibodies in human sera by ELISA. Sera were obtained from
      healthy individuals, asymptomatic carriers of N. meningitidis and cases of
      meningococcal disease. Healthy individuals had little detectable antibody to TBPs
      but sera from carriers and cases exhibited a response demonstrating that TBPs are
      expressed in vivo during both carriage and disease. The ELISA absorbances
      produced by each of the individual sera to TBPs from the three meningococcal
      strains were compared and very high correlation coefficients were obtained,
      indicating that human anti-TBP antibodies, in contrast to mouse and rabbit
      antibodies, are cross-reactive between strains. Antibodies to separately purified
      TBP1 and TBP2 were also detected in both cases and carriers. The IgG and IgM
      response to TBP1 + 2 was greater in cases than carriers but the mean IgA response
      was the same. This demonstration of an antibody response that is cross-reactive
      between TBP types greatly strengthens the case for inclusion of TBPs in a
      meningococcal vaccine to protect against all serogroups and serotypes.

PMID- 8578806
TI  - Neisseria gonorrhoeae IgA1 proteases share epitopes recognized by neutralizing
      antibodies.
AB  - The antigenic diversity among IgA1 proteases of 61 Neisseria gonorrhoeae strains
      isolated during a period of 23 years and on four continents was examined in
      enzyme neutralization assays employing rabbit antisera raised against selected
      IgA1 proteases. The antigenic analyses were compared with results of iga gene
      region RFLP patterns and enzyme cleavage specificity for substrate IgA1. Type 1
      IgA1 proteases were antigenically uniform while six different antigenic types
      were detected among type 2 enzymes. Extensive cross-reactions of antibodies
      against the different antigenic types suggested only minor differences in
      relevant epitopes. Epitopes previously found to be common to all Neisseria
      meningitidis IgA1 proteases were also shared by all N. gonorrhoeae IgA1 proteases
      in the collection. Human sera from patients with gonorrhoea showed broadly cross
      reactive neutralizing activity at titers comparable to those of sera from
      immunized rabbits. In conclusion, N. gonorrhoeae IgA1 proteases show a remarkable
      lack of diversity of epitopes recognized by enzyme-neutralizing antibodies. If
      future studies confirm that cleavage of IgA1 is an important step in gonococcal
      infections, Neisseria IgA1 proteases may be attractive vaccine candidates.

PMID- 8578807
TI  - Role of lipopolysaccharide and a major outer membrane protein from Francisella
      tularensis in the induction of immunity against tularemia.
AB  - A crude outer membrane preparation from Francisella tularensis Live Vaccine
      Strain (LVS) was used to immunize mice. Immunized mice were completely protected
      from a F. tularensis challenge. We evaluated the role of two major outer membrane
      antigens in the induction of protective immunity, namely lipopolysaccharide and
      an outer membrane protein FopA. We presented FopA to the immune system using an
      aromatic amino acid-dependent Salmonella typhimurium as a vector. Although mice
      mounted an immune response to cloned FopA no significant protection was induced.
      However, LPS immunized mice were completely protected. We conclude that LPS is a
      major protective antigen whereas FopA has a limited or no role in the induction
      of protective immunity.

PMID- 8578808
TI  - Lack of correlation between serum rotavirus antibody titers and protection
      following vaccination with reassortant RRV vaccines. US Rotavirus Vaccine
      Efficacy Group.
AB  - In a large placebo-controlled efficacy trial of the rhesus tetravalent (RRV-TV)
      and serotype 1 monovalent (RRV-S1) rotavirus vaccines in multiple sites
      throughout the United States, protection against rotavirus disease over a 2-year
      period was found to be 57 and 40%, respectively (Bernstein et al., J. Am. Med.
      Assoc., 1995, 273, 1191-1196). Sera collected from a subset of subjects during
      this trial were used to determine possible correlations between rotavirus
      antibody responses after vaccination and protection. Between 82% (RRV-S1) and 92%
      (RRV-TV) of the vaccinees seroconverted by at least one of the six antibody
      assays performed (i.e. rotavirus IgA and neutralizing antibody to RRV and
      serotype 1-4 human rotaviruses). Rises in neutralizing antibody were due
      primarily to RRV. The seroconversion rate was only 18-22% to each of the four
      human rotavirus serotypes following RRV-TV vaccination and was only 43% to
      serotype 1 human rotavirus after RRV-S1 administration. Furthermore, no correlate
      of immunity against rotavirus infection or disease was identifiable based on
      seroconversion to any of the antibodies measured. Likewise, no consistent
      relationship was found between the titers of any of these six antibodies
      following vaccination and protection against rotavirus, thus suggesting that
      serum antibody titers will not be useful markers of protection with these
      reassortant RRV vaccines. In addition, vaccinated subjects did not develop higher
      titers of neutralizing antibody to human rotaviruses following a subsequent
      natural rotavirus illness, a further indication that only weak immune responses
      to human rotaviruses were stimulated by vaccination with the RRV
      reassortants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8578809
TI  - A new epitope presenting system displays a HIV-1 V3 loop sequence and induces
      neutralizing antibodies.
AB  - The principal neutralizing domain, IGPGRAF sequence, from the V3-loop of HIV-1
      was inserted in two positions on the surface of the protein that makes up the
      capside shell of the insect Flock House Virus. The hybrid proteins were expressed
      in insect cells via recombinant baculoviruses. Three different hybrids were used
      as immunogens: two with a single copy of the insert in different positions of the
      carrier protein and a third with two copies of the insert at the same positions
      as before. All hybrid proteins induced strong and broad specific immune response
      in guinea pigs against different V3-loop sequences. However, only one of the
      hybrid proteins was able to induce a strong neutralizing response against MN and
      IIIB HIV-1 isolates. Our results demonstrate that a very short peptide sequence
      of HIV-1 can constitute a valuable immunogen able to induce a neutralizing
      response if presented to the immune system in the context of the FHV capsomer
      structure.

PMID- 8578810
TI  - Hepatitis B vaccination: universal vaccination of newborn babies and children at
      12 years of age versus high risk groups. A comparison in the field.
AB  - From 1983 to 1993 two anti-hepatitis B vaccinal strategies were adopted in two
      small towns of Southern Italy at high incidence for HBV infections: Afragola
      (prevalence of HBsAg carriers of 13.4%) and Frattamaggiore (prevalence of HBsAg
      carriers of 12.9%). In Afragola, the universal vaccination of infants in their
      first year of life and adolescents at 12 years of age was carried out, while in
      Frattamaggiore the selective vaccination of high risk groups of population was
      introduced. During this study, the changes in the HBV infection endemicity in
      both towns has been tested by monitoring the incidence of new cases of viral
      hepatitis B and by the prevalence study of HBsAg carriers prior to and 10 years
      after the beginning of the immunization programme (1978-1993). The results
      suggest that universal vaccination of infants in the first year of life and
      adolescents at 12 years of age has a greater efficiency on the improvement on the
      endemic status of the infection in the general population in comparison with
      selective vaccination, when the incidence of new cases of disease and the
      prevalence of number of HBsAg and anti-HBc carriers in the two populations are
      considered.

PMID- 8578811
TI  - An experimental rabies vaccine produced with a new BHK-21 suspension cell culture
      process: use of serum-free medium and perfusion-reactor system.
AB  - An experimental rabies vaccine was prepared from the BHK-21 cell line adapted to
      culture in suspension using bioreactors. A new serum-free medium (MDSS2) (Merten
      et al., Cytotechnology, 1994, 14, 47) developed for the culture of various cell
      lines and for the production of several biologicals, was used for cell culture
      and virus production. The PV-Paris/BHK-21 rabies virus strain (adapted to the BHK
      21 grown in monolayer) was adapted to BHK-21 cells cultivated in suspension and
      in the serum-free medium. High titres of rabies virus were obtained with
      bioreactors equipped with a perfusion system using BHK-21 cells grown in
      suspension in MDSS2. Experimental vaccines were prepared and had satisfactory
      protective activity when tested in mice. This new and low cost technology for
      rabies vaccine production could be suitable for developing countries where rabies
      is an important health problem.

PMID- 8578812
TI  - Mice immunized with a dengue type 2 virus E and NS1 fusion protein made in
      Escherichia coli are protected against lethal dengue virus infection.
AB  - A gene fragment encoding the C-terminal 204 amino acids (AA) from the structural
      envelope glycoprotein (E) and the N-terminal 65 AA from non-structural protein
      one (NS1) of dengue type 2 virus (DEN-2) was expressed in Escherichia coli (E.
      coli) as a fusion protein with staphylococcal protein A. The recombinant fusion
      protein was purified and analysed for its antigenicity, its immunogenicity and
      its ability to protect mice against lethal challenge with live DEN-2 virus. The
      recombinant protein was found to be reactive with anti-DEN-2 polyclonal and
      monoclonal antibodies. Mice immunized with the purified fusion protein made anti
      DEN-2 antibodies measured by the hemagglutination-inhibition (HI) and
      neutralization (N) tests, and were protected against lethal challenge with DEN-2
      virus administered by intracranial inoculation.

PMID- 8578814
TI  - Establishment of a SCID mouse model having circulating human red blood cells and
      a possible growth of Plasmodium falciparum in the mouse.
AB  - Our previous study has demonstrated that repeated transfusions of bovine red
      blood cells (RBCs) into SCID mice resulted in a complete substitution of their
      circulating RBCs. Identical experiments with human (Hu) RBCs, however, gave rise
      to a poor RBC-substitution because of the rapid elimination of Hu-RBCs from the
      circulation of SCID mice. Search for substances to decelerate the Hu-RBC
      clearance picked up some effective polysaccharides, such as sulfated chitin and
      mannan, but they were not effective enough to achieve a high level of Hu-RBC
      substitution. In the present study, we found that Hu-serum significantly extended
      the lifetime of Hu-RBC in SCID mice and that repeated transfusions of the mice
      with Hu-RBCs, in combination with Hu-serum administration, resulted in an almost
      complete substitution of their circulating RBCs. An Hu-RBC-substituted SCID mouse
      inoculated with Plasmodium falciparum had a parasitemia persisting for two weeks,
      indicating a possible growth of this parasite in the mouse. Thus, this report
      gave the first demonstration of a complete substitution of the circulating RBCs
      in SCID mice with Hu-RBCs and of a successful P. falciparum infection in the
      mice.

PMID- 8578813
TI  - Varicella vaccine.

PMID- 8578815
TI  - Maintenance of high virus load even after seroconversion in newborn cats acutely
      infected with feline immunodeficiency virus.
AB  - The viral loads in adult and newborn cats have been compared following injection
      with feline CD4+ FeL-039 line cells acutely infected with feline immunodeficiency
      virus (FIV). The level of virus genome in peripheral blood mononuclear cells
      (PBMC) increased progressively despite seroconversion in the newborn cats,
      whereas the virus genome was apparently cleared after seroconversion in the adult
      cats. Immunohistochemical staining of thymus of the FIV-infected newborn cats
      showed clusters of viral antigen-positive cells. These results indicate that FIV
      infection of the newborn cat results in higher virus loads than infection of the
      adult cat. We discuss these findings in relation to FIV as a model system for
      studies of the infection of neonates with an immunosuppressive retrovirus.

PMID- 8578816
TI  - Protection of mice against influenza A virus challenge by vaccination with
      baculovirus-expressed M2 protein.
AB  - We have investigated the potential of the conserved transmembrane M2 protein of
      influenza A/Ann Arbor/6/60 virus, expressed by a baculovirus recombinant, to
      induce protective immunity in BALB/c mice. Vaccination of mice with M2 shortened
      the duration of virus shedding and protected mice from a lethal infection with
      A/Ann Arbor/6/60 virus but not B/Ann Arbor/1/55 virus, suggesting that the
      protection was mediated by an M2-specific mechanism. Serum antibodies were
      detected which reacted with synthetic peptides defining three antigenic
      determinants located on both the external N- and internal C-termini of the M2
      protein. Furthermore, vaccination with M2 protected mice from death following a
      lethal challenge with the heterologous A/Hong Kong/68 (H3N2) virus. These results
      demonstrate the potential to elicit heterosubtypic immunity to type A influenza
      viruses through vaccination with a conserved transmembrane protein.

PMID- 8578817
TI  - Structure/function studies of QS-21 adjuvant: assessment of triterpene aldehyde
      and glucuronic acid roles in adjuvant function.
AB  - QS-21, a purified Quillaja saponaria saponin immunologic adjuvant, contains two
      functional groups that we hypothesized to be involved in the adjuvant mechanism
      of action through charge or Schiff base interaction with a cellular target.
      Derivatives, prepared by modification of these sites, were prepared and tested
      for their ability to augment the immunogenicity of the antigen ovalbumin (OVA) in
      C57BL/6 mice. QS-21 derivatives that were modified at the carboxyl group on an
      anionic sugar, glucuronic acid, retained adjuvant activity for antibody
      stimulation, inducing relative increases in antibody titers similar to those
      induced by QS-21, although the minimum adjuvant dose required for this
      stimulation was increased several fold relative to the dose of unmodified QS-21.
      One of these derivatives also retained significant activity for induction of OVA
      specific cytotoxic T-lymphocytes. In contrast, QS-21 derivatives modified at an
      aldehyde on the triterpene did not show adjuvant activity for antibody
      stimulation or for induction of cytotoxic T-lymphocytes, suggesting that this
      functional group may be involved in the adjuvant mechanism.

PMID- 8578818
TI  - Enhancement of protective immune responses to Venezuelan equine encephalitis
      (VEE) virus with microencapsulated vaccine.
AB  - Venezuelan equine encephalomyelitis (VEE) virus is a mosquito-borne arbovirus of
      major human health significance in the New World. Currently two forms of VEE
      virus are used for immunization of humans and horses, i.e. a live attenuated and
      a formalin-inactivated vaccine. Clinical evidence suggests that these vaccines
      are not fully efficacious and may produce certain undesirable side-effects. In
      the present study, microspheres composed of biocompatible and biodegradable poly
      (DL-lactide-co-glycolide) (DL-PLG) were evaluated for their effectiveness as a
      delivery system of whole, inactivated VEE virus vaccine for the induction of
      protective immune responses. Mice receiving 50 micrograms VEE virus in
      microspheres composed of an equimolar ratio of DL-lactide and glycolide (50:50 DL
      PLG) exhibited a primary circulating IgG antibody response which was
      approximately 32-times higher than the response induced with the same dose of
      unencapsulated (free) virus. A similar difference in responses was seen with
      antigen doses ranging from 3.1 to 50 micrograms. A rapid increase in antibody
      activity was seen after the secondary immunization (day 50). Formalin fixation of
      inactivated VEE virus was important for immunogenicity since the circulating anti
      VEE virus antibody response induced with microencapsulated nonformalin-fixed
      virus vaccine was lower than that induced with microencapsulated formalin-fixed
      virus vaccine. Furthermore, at low antigen concentrations, DL-PLG microsphere
      vaccines prepared with the solvent methylene chloride induced higher antibody
      responses than those prepared using ethyl acetate as the solvent.
      Microencapsulated vaccine also induced higher VEE virus neutralization titers
      than did free virus vaccine. Finally, the microencapsulated virus was more
      effective than the free virus in inducing immune responses protective against
      systemic challenge with virulent VEE virus. These results demonstrate that DL-PLG
      microspheres containing formalin-fixed, inactivated VEE virus were effective in
      augmenting circulating IgG antibody levels and neutralization titers to the VEE
      virus following systemic immunization and in affording enhanced protection
      against systemic challenge with virulent VEE virus. The effects of antigen form
      and the microsphere processing solvent on the immunogenicity of the vaccine are
      discussed.

PMID- 8578819
TI  - Immunological evaluation of three generations of anti-idiotype vaccine: study of
      B and T cell responses following priming with anti-idiotype, anti-idiotype
      peptide and its MAP structure.
AB  - A 15mer peptide (2F10 peptide) is capable of mimicking the group specific "a"
      determinant of human hepatitis B surface antigen (HBsAg), both at the B and T
      cell level. This peptide represents a sequence on the heavy-chain hypervariable
      region of a monoclonal "internal image" anti-idiotype (anti-id) 2F10 that has
      partial sequence homology to the "a" determinant epitope of HBsAg. In order to
      potentiate the immunological properties of 2F10 peptide, a synthetic polymer of
      the 2F10 peptide was constructed (2F10 MAP). In this study we present the
      immunological evaluation of three generations of anti-idiotype vaccines, namely
      the 2F10 anti-id, 2F10 peptide and 2F10 MAP. Our results indicate that there is
      significant anti-HBs production in mice immunized with 2F10 anti-id or 2F10 MAP,
      in comparison to mice immunized with the linear monomeric 2F10 peptide. In
      priming experiments we found that only 2F10 antibody or 2F10 MAP (both at a
      suboptimal dose), could effectively prime B cells in vivo which could be
      efficiently recalled by challenge with a suboptimal dose of HBsAg. Collectively
      our findings indicate that 2F10 MAP retains all the immunological properties of
      the intact anti-id, and is qualitatively similar and quantitatively superior to
      the linear monomeric 15mer 2F10 peptide. The 2F10 MAP is the smallest MAP
      structure composed of a naturally occurring contiguous sequence having both a B
      and T cell epitope capable of eliciting a response to the native antigen.

PMID- 8578820
TI  - Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T
      lymphocyte responses following epidermal delivery of nanogram quantities of DNA.
AB  - Particle-mediated (gene gun) DNA transfer to the epidermis was evaluated for its
      ability to elicit humoral and cytotoxic T lymphocyte responses using decreasing
      quantities of plasmid DNA-based antigen expression vectors. Using plasmids
      encoding human growth hormone, human alpha-1-antitrypsin, and influenza virus
      nucleoprotein, strong immune responses were observed in mice following
      immunization with as little as 16 ng of DNA using an electric discharge gene
      delivery system. Significant antibody titers were observed against these antigens
      following a primary immunization, with responses rising dramatically following a
      boost. Increasing the DNA dose above 16 ng per immunization had little beneficial
      effect. In contrast to particle-mediated DNA delivery, intramuscular or
      intradermal inoculation required greater than 5000-fold more DNA to achieve
      comparable results. Data are also presented demonstrating that a simple, hand
      held version of the Accell DNA delivery system, employing compressed helium as
      the particle motive force, achieves immune responses comparable to the
      traditional electric discharge device.

PMID- 8578821
TI  - Stabilising oral poliovaccine at high ambient temperatures.
AB  - The oral poliovaccine strains lose infectivity when they are stored above
      refrigerator temperatures. These losses increase rapidly at the high temperatures
      encountered in tropical countries, thus causing problems if the cold chain is
      inadequate. Attempts to minimise these losses have generally relied on the
      addition of salts such as MgCl2. In this paper we show that the fall in
      infectivity, which is due to the hydrolysis of the genomic RNA by the RNA
      polymerase within the virus particle, can be greatly inhibited by the suppression
      of this enzymatic activity. This can be achieved simply by reducing the pH below
      7.

PMID- 8578822
TI  - Construction and evaluation of a virG thyA double mutant of Shigella flexneri 2a
      as a candidate live-attenuated oral vaccine.
AB  - A virG thyA double mutant of Shigella flexneri 2a was constructed as a candidate
      live-attenuated oral vaccine. In the keratoconjunctivitis model it did not
      provoke any adverse reaction by itself on guinea pigs' eyes and completely
      protected them from provoking keratoconjunctivitis. When (2.7-4.8) x 10(10) of
      the vaccine was inoculated intragastrically after 1 day fasting in cynomolgus
      monkeys three times at weekly intervals, a watery stool was observed at 40% as a
      side-effect. Upon intragastric challenge after 1 day fasting with 7.5 x 10(9) of
      the virulent strain four weeks after the last vaccination, a statistically
      significant difference was obtained in the mortality rate but not in the
      morbidity rate between the vaccine and the control group, although the clinical
      findings were less severe in the vaccine group than in the control group. These
      results together with the histopathological and immunological findings indicate
      that the vaccine deserve further detailed studies.

PMID- 8578823
TI  - Accurate determination of adjuvant-associated protein or peptide by ninhydrin
      assay.
AB  - Modern peptide and subunit vaccines are increasingly having to rely on the use of
      immunological adjuvants to achieve effective immunity. However, the only adjuvant
      currently approved for use in humans is aluminium hydroxide, although many
      adjuvants are currently under preclinical development. Determining immunogen
      concentration in the presence of adjuvants such as aluminium hydroxide gel,
      liposomes or NISV has proved to be problematic. One approach has been to use
      radiolabelled antigens to extrapolate concentration to a preparation using native
      immunogen. However, the use of a colorimetric assay would allow greater
      flexibility in terms of immunogen used and would reduce costs and remove safety
      problems. Of the colorimetric methods we have examined thus far, only the manual
      ninhydrin assay has produced consistent results with detection of microgram
      quantities of protein or peptide in the presence of NISV or Alhydrogel, but not
      liposomes. As the assay relies on the detection of free amino groups after
      protein hydrolysis, peptides as well as proteins may be effectively determined
      irrespective of amino acid composition, a considerable advantage over other
      colorimetric assay systems.

PMID- 8578824
TI  - Dehydroepiandrosterone (DHEA) treatment reverses the impaired immune response of
      old mice to influenza vaccination and protects from influenza infection.
AB  - Dehydroepiandrosterone (DHEA) is a native steroid with an immunomodulating
      activity. Recently it was suggested that its age-associated decline is related
      with immunosenescence. To examine whether DHEA administration could effectively
      reverse the age-associated decline of immunity against influenza vaccine, aged
      mice were simultaneously vaccinated and treated with DHEA. Reversal of the age
      associated decline and a significant constant increase of humoral response was
      observed in treated mice. Increased resistance to post-vaccination intranasal
      challenge with live influenza virus was observed in DHEA-treated aged mice. Thus,
      DHEA treatment overcame the age-related defect in the immunity of old mice
      against influenza.

PMID- 8578825
TI  - Passive immunotherapy in neonatal calves--I. Safety and potency of a J5
      Escherichia coli hyperimmune plasma in neonatal calves.
AB  - A pair of studies designed to assess the clinical safety and potency of
      hyperimmune plasma administration was undertaken in neonatal calves. Bovine
      plasma from Holstein heifers hyperimmunized with a mutant Escherichia coli
      O111:B4 (J5) vaccine which had a geometric mean (GM) immunoglobulin G (IgG) ELISA
      titer of 3.5 x 10(4), was administered subcutaneously to < or = 2-day-old calves.
      In the first (study A) of two prospective trials, hyperimmune plasma was
      administered in two doses to colostrum-deprived (CD) (n = 7) and colostrum-fed
      (CF) (n = 16) neonatal dairy calves. Data were collected immediately before (0 h)
      and 6, 24, 48, 72, 96, 120 and 288 h after the first plasma administration. Total
      serum protein and serum IgG concentration elevated in both groups with a
      significant (p < 0.01) rise of E. coli J5-specific IgG from the corresponding
      baseline by 6 h post-plasma administration. In the second (study B) trial, calves
      (N = 75) allocated into three protocol groups received two doses of either the
      hyperimmune (TT) J5 plasma (n = 30) or the control (CT) plasma (n = 30), and the
      third group (NT) received no plasma (n = 15). Data were collected up to 96 h post
      plasma administration. Serum IgG and J5 specific ELISA antibody titer increased
      significantly (p < 0.01) in TT calves compared to the other group calves. The
      endotoxin contents of the administered plasma were < or = 1 EU ml-1 by limulus
      amebocyte lysate (LAL) method and the collected physiological and hematological
      data values were similar in all groups in both trials. In addition, no immediate
      adverse reaction or death was observed in any phase of the plasma administration.
      The E. coli J5 hyperimmune bovine plasma, as prepared and administered to
      neonatal calves in the current trials, proved to be a safe and potent biomedical
      fluid.

PMID- 8578826
TI  - Passive immunotherapy in neonatal calves--II. The efficacy of a J5 Escherichia
      coli hyperimmune plasma as immunotherapy in neonatal calves.
AB  - Hyperimmunized bovine plasma containing antibodies to a mutant Escherichia coli
      O111:B4 (J5) was used to conduct a prospective double-blind clinical trial to
      evaluate its efficacy as an immunotherapy to bovine neonates in field conditions.
      Two- to three-day-old calves (N = 150) were randomized into three groups (n = 50)
      to receive (1) no plasma (NP) or (2) control (traces or no J5 antibody) bovine
      plasma (CP), or (3) hyperimmune bovine anti J5 plasma (HP) in two subcutaneous
      total doses of 10 ml kg-1 body weight at a 24 h interval. Various physiological,
      pathological and clinical parameters of the study subjects were observed up to
      three weeks while other data such as morbidity, mortality and the effect on heart
      girth increase were collected up to the end of the eighth week. Weekly serum
      total protein and immunoglobulin G (IgG) concentrations were preferentially
      increased from the baseline values in HP calves but not statistically significant
      (p > 0.05) in group comparison. Mean (geometric) serum J5 ELISA titers in the HP
      group were significantly (p < 0.001) higher than the other two groups that
      increased about 1-log by the first week of plasma intervention, followed by a
      gradual decline by the third week. Out of three total deaths due to septicemia
      and colitis, one was from the NP group while the other two were from the HP
      group. Morbidity as measured daily on a 13-point scoring scale were not
      statistically (p > 0.05) different among the groups. Variation in the mean heart
      girth increase was non-significant (p > 0.05) among groups by the eighth week.
      Higher increase in heart girth was generally associated with higher initial serum
      IgG (p < 0.01) concentration. Our results suggest that this lot of hyperimmune J5
      plasma at this dose was not superior to control plasma or to no intervention in
      terms of calf morbidity and mortality.

PMID- 8578827
TI  - Peptide polymerisation facilitates incorporation into ISCOMs and increases
      antigen-specific IgG2a production.
AB  - Synthetic peptides can be tailor-made to include any B or T epitopes desired from
      a single or multiple antigens or organisms. However, peptides in general are not
      very immunogenic and have not proven easy to incorporate into immunogenic
      vaccines. ISCOMs is an adjuvant system that has the capability not only to
      enhance the humoral immunogenicity of a protein but has also been shown to induce
      cell-mediated immune responses in animals. Synthetic peptide ISCOM vaccines are
      few because of the difficulty in incorporation of these peptides into ISCOMs. We
      have shown in this study that non-immunogenic peptides could be made immunogenic
      by polymerisation, and these polymers could be incorporated into ISCOMs to give
      highly immunogenic vaccines. Synthetic 20mer peptides containing known B and T
      helper epitopes from the E7 protein of the cervical cancer associated human
      papillomavirus type 16 (HPV16 E7) have been used here as model immunogens. We
      have compared the humoral immunity induced by these peptides as polymers or as
      copolymers with a lipid binding 20mer peptide (LAP 20), with or without
      incorporation into ISCOMs. Unpolymerised peptide elicited no measurable antibody.
      When polymerised peptide was administered with CFA, or in phosphate-buffered
      saline (PBS) without adjuvant, or incorporated into ISCOMs, antibodies
      recognising both the immunising peptide and HPV16 E7 protein were produced. For
      equal quantities of administered peptide (5 micrograms), ISCOMs gave higher
      titres of antibody than CFA or PBS. Polymerised peptides induced high antigen
      specific IgG2a:IgG1 ratios, which increased with multiple immunisations. These
      data indicate that polymerised peptides could be incorporated into ISCOMs to form
      efficient immunogens which may elicit a Th1 type response.

PMID- 8578828
TI  - Receptor specificity of influenza virus influences severity of illness in
      ferrets.
AB  - Weanling ferrets were inoculated intranasally with either wild-type or receptor
      variant clones of influenza A/Memphis/102/72 to determine if changes in receptor
      specificity influence virulence of influenza virus infection. Over the 5 days
      after inoculation, receptor-variant inoculated ferrets had a lower mean elevation
      in body temperature, greater weight gain and less sneezing than the wild-type
      group. Influenza virus was recovered from the lungs of fewer receptor-variant
      infected ferrets (5/12 vs 11/12) and in lower titers than in wild-type infected
      ferrets at 5 days after inoculation. The viruses recovered from lung homogenates
      retained the same receptor specificity as the inoculum. Serum hemagglutination
      inhibition titers for the two groups were similar. These findings suggest that
      the receptor-variant clone is less virulent but elicits a similar immunogenic
      response compared with the wild-type clone.

PMID- 8578829
TI  - Fine specificity of immune responses to epitopic sequences in synthetic peptides
      containing B and T epitopes from the conserved Plasmodium falciparum blood-stage
      antigens.
AB  - Immunisation with two chemically synthesised, linear, multiple epitope peptides
      (MEP) containing B and T cell epitopes from two conserved blood-stage antigens of
      the human malaria parasite, Plasmodium falciparum, induced high levels of
      circulating antibodies without the use of a carrier protein. Immunisation of
      BALB/c mice with MEP constructs (P1 and P2) induced antibodies against the
      various epitope sequences included in their structures, although the immune
      response was focused more towards the N terminal and the middle portion of the
      peptides. In vitro T cell proliferation assays indicated that only one of the two
      Th epitopes included in P1 and P2 are functional. Both P1 and P2, based on P.
      falciparum sequences, cross-reacted with sera from P. yoelii-infected mice.
      Immunisation with P1 in CFA, but not with P2, provided partial protection to
      BALB/c mice against P. yoelii challenge infection. Peptide P1 was highly
      immunogenic in alum also, and a somewhat higher level of protection was observed
      as compared to CFA immunisation. We found that immunisation with P1 induced
      antibody responses in different strains of mice, although to different extents.
      These results suggest that linear, multiple epitope peptides may offer attractive
      alternatives as subunit vaccine candidate molecules, but at the same time
      highlight the fact that the design principles are far from being clear and have
      yet to be worked out.

PMID- 8578830
TI  - Inability to reproduce protection against Teladorsagia circumcincta in sheep with
      a purified stage-specific 31 kDa antigen complex.

PMID- 8578831
TI  - A modified Shigella volunteer challenge model in which the inoculum is
      administered with bicarbonate buffer: clinical experience and implications for
      Shigella infectivity.
AB  - In the absence of a definitive immunologic correlate of protection against
      shigellosis, promising Shigella vaccine candidates have been selected based on
      their ability to confer resistance against experimental challenge with wild-type
      Shigella in healthy adult volunteers. A limitation of this model has been the low
      and often variable attack rate of illness among controls, necessitating repeated
      inpatient studies to demonstrate statistically significant results. In this
      study, the Shigella challenge model was modified by using bicarbonate buffer
      instead of skimmed milk as the delivery vehicle to enhance survival of the
      ingested challenge inoculum. To determine the ability of the modified model to
      detect protective efficacy, 11 veteran volunteers (previously challenged with S.
      flexneri 2a in bicarbonate buffer) and 12 immunologically naive control subjects
      were challenged with 1.4 x 10(3) c.f.u. S. flexneri 2a. Shigellosis occurred in 3
      veterans and 11 control subjects (27 vs 92%, p = 0.003), yielding a protective
      efficacy of 70%. Dose response was evaluated in an additional seven naive
      subjects who were inoculated with a log lower (1.4 x 10(2) c.f.u.) S. flexneri 2a
      and had a significantly diminished attack rate of shigellosis (317 (43%) vs 11/12
      (92%), p = 0.04). These findings indicate that the modified bicarbonate challenge
      model using an inoculum of 10(3) c.f.u. is a safe, repeatable, and valid method
      of selecting Shigella vaccines and other immunoprophylactic agents that are
      likely to confer protection against natural shigellosis.

PMID- 8578832
TI  - Induction of systemic immune responses to measles virus synthetic peptides
      administered intranasally.
AB  - A systemic antibody response was induced when a chimeric peptide containing two
      copies of a promiscuous T-cell epitope and one copy of a B-cell epitope (TTB)
      from the fusion protein of measles virus (MV) was administered to mice
      intranasally without adjuvant. A higher antibody titre was produced when the
      peptide was administered intranasally with cholera toxin B subunit (CTB) as an
      adjuvant and these antibodies crossreacted with the MV. Furthermore, splenocytes
      from intranasally immunized mice proliferated in vitro in the presence of the TTB
      peptide. The immune response following intranasal immunization with the peptide
      was influenced by the MHC haplotype of the strain of mice used. Thus CBA and
      BALB/c mice were high responders whereas C57BL/6 mice were low responders.
      Although peptide administered intranasally with CTB to CBA mice induced an immune
      response, no significant protection was observed against intra-cranial challenge
      with canine distemper virus which is antigenically related to MV.

PMID- 8578833
TI  - The antibody response to a prototype liposome vaccine containing Neisseria
      meningitidis outer membrane protein P1 produced in Bacillus subtilis.
AB  - Monoclonal antibodies to the class 1 outer membrane protein P1 of Neisseria
      meningitidis B:15:P1.7,16 have been shown to be bactericidal and protective in an
      infant rat meningitis model. We have produced the P1 protein in Bacillus subtilis
      as inclusion bodies. When the purified and denatured protein (BacP1) was
      reconstituted with phosphatidylcholine into liposomes, native antigenic epitopes
      were formed. Such liposomes were reproducibly immunogenic in mice and guinea pigs
      at a low dose (1-10 micrograms of BacP1 protein) and without any other adjuvant.
      The resulting antisera contained high titers (enzyme immunoassay) of antibodies
      directed to native P1 epitopes exposed on the surface of meningococcal cells. The
      sera were also active with live N. meningitidis in bactericidal assays and
      protective in the infant rat meningitis model; all these activities were specific
      to the serosubtype of the P1 protein.

PMID- 8578834
TI  - Vaccination with yeast-expressed cottontail rabbit papillomavirus (CRPV) virus
      like particles protects rabbits from CRPV-induced papilloma formation.
AB  - Papillomaviruses infect epithelia of the skin and mucous membranes and cause
      benign or malignant tumours in animals and in humans. The viruses are highly
      species-specific, and cell culture systems for propagating human papillomaviruses
      (HPVs) do not exist. However, there are several animal papillomavirus models. In
      the cottontail rabbit papillomavirus (CRPV) system, we demonstrated that
      recombinant CRPV virus-like particles (VLPs) consisting of the capsid proteins L1
      or L1+L2 can be produced in the yeast Saccharomyces cerevisiae. Three
      immunizations with L1 VLPs formulated on aluminum adjuvant at 1-100 micrograms
      dose-1 efficiently protected rabbits from challenge with CRPV. Sera of immunized
      rabbits were shown to contain high-titered serum antibodies to CRPV L1 VLPs and
      to neutralize CRPV in vitro. Our results suggest that recombinant yeast-derived
      VLPs could be the basis for a candidate HPV vaccine.

PMID- 8578835
TI  - Finer mapping of neutralizing epitope(s) on the C-terminal of Japanese
      encephalitis virus E-protein expressed in recombinant Escherichia coli system.
AB  - In order to localize denaturation-resistant neutralizing epitope(s) in the C
      terminal 180 amino acids of Japanese encephalitis (JE) virus E-protein, four
      recombinant clones encoding different or overlapping nucleotide sequences were
      constructed by PCR from a recombinant plasmid pS22. The amplified fragments were
      cloned into PCR 1000 vector, and then transferred into Escherichia coli
      expression vector pRIT2T. The inserted genes were expressed as fusion proteins
      with protein-A and examined for their antigenicity and immunogenicity by Western
      blotting and mouse immunization, respectively. Among the four recombinant fusion
      proteins, the highest neutralizing antibody titre was obtained by the one
      expressed by the recombinant clone pRIT2T-B3, which carried the coding sequence
      of amino acid number 373-399 of JE virus E protein. The results indicated that
      this short region of 27 amino acids sequence near the C-terminal of JE virus E
      protein possesses neutralizing epitope(s). These data should assist in the design
      of an efficient subunit vaccine against JE virus infection in future.

PMID- 8578836
TI  - Cross-reaction but no avidity change of the serum antibody response after
      influenza vaccination.
AB  - Pre- and post-vaccination sera from 19 volunteers were analysed by the
      haemagglutination inhibition (HI) test, virus neutralization (VN) assay and
      avidity enzyme-linked immunosorbent assay (ELISA). The sera were tested against
      the three strains in a commercial inactivated influenza vaccine;
      A/Beijing/353/89(H3N2); A/Taiwan/1/86 (H1N1) and B/Yamagata/16/88. Additionally,
      a range of earlier strains and one newer isolate were assayed for HI- and VN
      antibodies. Large variations in the pre-vaccination HI titres were observed for
      the viruses tested. However, 8-9 days after vaccination HI titres increased to
      above the assumed protective level (HI > or = 40) in most subjects. Although a
      limited number of patients were analysed at each sampling point, the time-profile
      we observed in this study is consistent with data we have obtained in earlier
      trials (Cox, R.J. et al., Vaccine 1994, 12,993-999). The VN titres, on the other
      hand, were low against all influenza strains before and up to 6 days, but
      increased rapidly 8-9 days after vaccination. A recent H3N2 isolate,
      A/Beijing/32/92 (H3N2), which had drifted further away from the vaccine strain,
      reacted to low titres or were negative in both the HI and VN assays. No change in
      the serum avidity to the influenza surface antigens was detected after
      vaccination, whereas sera from subjects naturally infected with influenza showed
      an increase in avidity to the infecting virus strain. The increase in serum
      avidity observed in the infected subjects is probably due to the increased and
      prolonged antigenic stimulus provided by the replicating virus.

PMID- 8578837
TI  - Absence of an association between rubella vaccination and arthritis in
      underimmune postpartum women.
AB  - In a double-blind historical cohort study, 485 underimmune women who received
      rubella vaccine post-partum during 1985-1990 and 493 controls matched for age,
      place of residence and date of delivery were queried by phone concerning joint
      complaints following the pregnancy in question. Those reporting joint symptoms
      were invited for a personal interview at which joint symptoms and dates of their
      occurrence were explored in detail. Nineteen women in the vaccinated group (3.9%)
      and 16 from the control group (3.2%) were judged to have had joint symptoms
      compatible with the study definition of arthritis. The difference was not
      statistically significant. Thus, we were unable to find evidence for an
      association between rubella vaccination of underimmune adult women vaccinated
      post-partum and the subsequent development of arthritis. Rubella vaccine should
      continue to be used to immunize susceptible adult women against rubella in order
      to further the goal of elimination of the congenital rubella syndrome.

PMID- 8578838
TI  - Immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in
      healthy children and in children at increased risk of pneumococcal infection.
AB  - Splenectomized children as well as those suffering from nephrotic syndrome or
      recurrent asthmatic bronchitis have an increased susceptibility to systemic
      pneumococcal infections compared to healthy children. To determine the
      immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine
      (PPV), 119 children (21 healthy, 26 splenectomized children, 48 with nephrotic
      syndrome and 24 with recurrent asthmatic bronchitis), aged 2-18 years, received
      one subcutaneous injection of a 23-valent PPV. Anti-capsular antibodies (Ab) to
      types 6B, 9V, 14, 18C, 19F and 23F were measured by ELISA before and 4 weeks
      after immunization. In all cases the adverse reactions were mild and transient,
      consisting of local pain and/or erythema or swelling in 41% and fever above 38.5
      degrees C in 2% of the children. The healthy children responded well to
      vaccination with a mean fold increase (FI) of 2.6 in postvaccination Ab titers
      compared to prevaccination titers. The combined geometric mean Ab concentrations
      in the high-risk children were significantly lower than those of healthy children
      both before and after vaccination. However, the combined geometric mean FI were
      not significantly different between high-risk and healthy children. These results
      indicate that PPV is immunogenic and safe in high-risk as well as in healthy
      Korean children.

PMID- 8578839
TI  - Immune response and protection against influenza A infection in mice immunised
      with subunit influenza A vaccine in combination with whole cell or acellular DTP
      vaccine.
AB  - Following the demonstration of the strong adjuvant effect of whole-cell DTP
      vaccine (wDTP) on the immune responses to influenza subunit vaccine, studies were
      undertaken to identify the component of wDTP responsible for the adjuvant effect,
      and to determine if acellular DTP (aDTP) vaccine was as effective since it is
      less reactogenic and likely to replace wDTP for primary or secondary
      immunisation. In addition, wDTP and aDTP were directly compared in a dose
      response study. Experiments in mice indicated that the adjuvant effect of wDTP
      resided in the LPS component of B. pertussis, since purified LPS enhanced the IgG
      antibody response, the IgG subclass response and protection to the same level as
      wDTP. An adjuvant effect was detected using aDTP, but was statistically less
      pronounced than wDTP by a factor of some 100-fold. These results suggest that
      immunisation against influenza in infants and young children can be achieved
      combining small amounts of influenza antigen with wDTP or LPS, and to a lesser
      extent by combining vaccine with aDTP. However, these results were obtained in
      mice and should be confirmed in man since species vary considerably in response
      to adjuvant.

PMID- 8578840
TI  - Antibody responses and symptoms after DTP and either tetanus or diphtheria
      Haemophilus influenzae type B conjugate vaccines given for primary immunisation
      by separate or mixed injection.
AB  - The safety and immunogenicity of two conjugate Haemophilus influenzae type B
      (Hib) vaccines administered either mixed with, or in separate limbs to, a whole
      cell DTP vaccine, was compared in infants vaccinated at 2, 3 and 4 months of age.
      Antibody titres to purified polyribosylribitol phosphate, diphtheria, and to
      pertussis antigens between infants who received the Hib and DPT vaccines in
      separate limbs or in the same limbs were similar (P > 0.1) while antibody titres
      to tetanus toxoid were higher in the later group (P < 0.05). This study
      demonstrated that both Hib vaccines can be mixed with whole-cell DTP vaccine
      without reducing immunogenicity of either vaccine or increasing the incidence of
      adverse reactions.

PMID- 8578841
TI  - A comparison of Plague vaccine, USP and EV76 vaccine induced protection against
      Yersinia pestis in a murine model.
AB  - The median lethal dose (MLD) of a pathogenic strain of Yersinia pestis was
      established by three routes of administration in three strains of mouse. There
      was no significant difference between the MLDs in the different strains of mouse.
      The MLD by the subcutaneous route in Balb/C and an outbred line was approximately
      1 c.f.u.; the MLD following intraperitoneal administration was tenfold higher.
      There were significant differences in the mean times to death after
      administration of the challenge by different routes. The relative efficacy of a
      live attenuated vaccine strain of Y. pestis (EV76) was compared with that of the
      formaldehyde-killed vaccine (Plague vaccine, USP). EV76 protected against high
      challenge doses (up to 5.75 x 10(6) MLD), though immunized animals showed side
      effects of varying severity. The killed vaccine was less effective in terms of
      dose-protection (deaths occurred after challenge with 4000 MLD) and several of
      the vaccinated animals suffered sub-lethal, plague-related sequelae to the
      challenge.

PMID- 8578842
TI  - Enhancement of humoral response against human influenza vaccine with the simple
      submicron oil/water emulsion adjuvant MF59.
AB  - Human influenza subunit vaccines are not fully protective in either the very
      young or elderly populations where risk is greatest. The use of an adjuvant to
      enhance antibody titer is an attractive option to increase vaccine efficacy. A
      series of squalene/H2O emulsions stabilized either by the amphipathic muramyl
      peptide MTP-PE (sodium N-acetyl-muramyl-L-alanyl-D-isoglutaminyl-L-alanyl-2
      (1',2'-dipalmitoyl- sn- glycero-3'phospho) ethylamide) or by mixtures of the
      sorbitan oleate surfactants Tween 80 and Span 85 have been tested as adjuvants
      with influenza vaccine. Combination of influenza vaccine with the Tween/Span
      stabilized emulsions has resulted in significantly higher antibody titers to
      vaccine in an extensive series of naive animal models. The use of submicron
      emulsion droplets is significant in determination of adjuvant activity while the
      presence of the muramyl peptide is not required for adjuvant activity. The 200
      300 nm diameter emulsion formulation MF59 containing only the low toxicity
      components squalene, Tween 80 and Span 85 has been shown to enhance titers from 5
      to 250 times that achievable with vaccine alone.

PMID- 8578843
TI  - Economic aspects of a general vaccination against invasive disease caused by
      Haemophilus influenzae type b (Hib) via the experience of the Children's Hospital
      La Fe, Valencia, Spain.
AB  - With the aim of studying whether a general vaccination against invasive disease
      caused by Haemophilus influenzae type b (Hib) is economically profitable bearing
      in mind the efficacy and safety of the vaccine, its price and the global cost
      that this disease has in our area, a review is conducted of patients admitted due
      to invasive disease caused by Hib in the Children's Hospital La Fe, Valencia,
      born between 1984 and 1993. They total 100, 63 who have meningitis. In the 81
      cases (56 with meningitis) born between 1984 and 1990 (years that can be regarded
      as "closed" since all the patients were younger than 5 years of age) the total
      cost has been calculated for hospitalization, care during the acute phase, care
      for the sequelae (6 severe and 7 mild) and death (5 cases). The mean annual cost
      of care can be calculated at 62 million pesetas, without making an economic
      valuation of the loss of life, and at 205 million pesetas taking this factor into
      account. The annual cost of vaccinating the 7000 babies under one year of age and
      falling within the Hospital's catchment area, on the basis of a vaccination
      pattern of three doses (at 2, 4 and 6 months) or four doses (at 2, 4, 6 and 15
      months) would amount to 63 or 84 million pesetas, normal price to public (not
      covered by National Health Service), and 40 or 51 million pesetas if acquired by
      National Health Service. As a conclusion we can state that, even from the
      economic point of view, without quantifying the cost of the loss of life, a
      public general anti-Hib vaccination would be profitable in our area since it
      would mean an administration cost lower than that of the care required by
      patients. This is without taking into account the fact that emotional, family and
      social serious disturbances would also be avoided due to hospitalization,
      sequelae and deaths caused by a disease which is today perfectly preventable.

PMID- 8578844
TI  - A multistep procedure for the chemical inactivation of human immunodeficiency
      virus for use as an experimental vaccine.
AB  - The kinetics of inactivation of four different strains of HIV-1 (RF, MN, SF2 and
      IIIB) by beta-propiolactone (BPL) and binary ethylenimine (BEI) were studied
      under various conditions. The conditions that would be required for the reduction
      of virus infectivity by at least 10(20) TCID50 ml-1 were estimated on the basis
      of the experimental rates of inactivation obtained. A multiple step procedure
      including treatment with 0.2% BPL, 0.05% sodium cholate, 10 mM BEI and 0.02%
      formaldehyde was designed to inactivate HIV-1 for use as an experimental vaccine.
      Complete inactivation of virus infectivity was confirmed by prolonged cell
      culture. The experimental vaccine preparation was analysed for the presence of
      HIV-1 proviral DNA utilizing the polymerase chain reaction. After treatment with
      both BPL and BEI proviral DNA was detected in one of four samples using primers
      encoding a 244 bp segment of the pol region of the viral genome. Proviral DNA
      could not be detected in any of the four samples using primers encoding segments
      of > 400 bp in the gag and reverse transcriptase region.

PMID- 8578845
TI  - Synthetic delivery system for tuberculosis vaccines: immunological evaluation of
      the M. tuberculosis 38 kDa protein entrapped in biodegradable PLG microparticles.
AB  - Tuberculosis remains a major public health burden which could be ameliorated by
      effective and well-defined subunit vaccines, particularly because the protective
      efficacy of current M. bovis BCG vaccines is both unpredictable and variable. The
      immunodominant 38 kDa antigen from Mycobacterium tuberculosis was entrapped in
      biodegradable poly (DL-lactide co-glycolide) (PLG) microparticles which served as
      a delivery system. Both cellular and humoral immune responses were assessed and
      compared with those obtained after immunization with the 38 kDa protein
      emulsified in incomplete Freund's adjuvant (IFA). Vaccination of mice with a
      single dose of antigen-loaded microparticles resulted in specific IgG titres
      peaking after five weeks comparable to those achieved after vaccination with
      protein emulsified in incomplete Freund's adjuvant (IFA). T-cell responses were
      found to be superior to those induced with antigen/IFA. The T- and B-cell epitope
      specificities ad judged with synthetic peptides were identical following
      immunization with antigen in microparticles or IFA. Differences in adjuvanticity
      were revealed by measuring antigen-specific IgG1, IgG2a and antigen-induced IFN
      gamma secretion in vitro: substantially higher titres of IgG2a were observed
      following immunization with antigen/microparticles than with 38 kDa protein/IFA.
      This was paralleled by a tenfold higher secretion of IFN-gamma in mice injected
      with antigen/microparticles. Reduction in colony-forming units was not consistent
      in mice immunized with 38 kDa protein entrapped in microparticles which were
      subsequently infected with live tubercle bacilli. Taken together these results
      indicate that biodegradable PLG microparticles constitute a favorable candidate
      vaccine delivery system worthy of further assessment in the quest to develop
      better and defined agents protecting against tuberculosis.

PMID- 8578846
TI  - Replicative advantage in tissue culture of egg-adapted influenza virus over
      tissue-culture derived virus: implications for vaccine manufacture.
AB  - Influenza virus derived from clinical material on MDCK cells has been shown to
      possess haemagglutinin (HA) indistinguishable from that of the natural,
      uncultivated virus. In contrast, viurs derived in embryonated hens' eggs are
      variants with substitutions in their HA in the vicinity of the receptor binding
      site. We report here the superior growth of egg-adapted virus over cell-derived
      virus on MDCK cells in studies in which MDCK-derived virus was spiked with small
      amounts of egg-adapted virus and the mixture sequentially passaged on MDCK cells.
      Such egg-derived variants bind to and are internalized by MDCK cells with a much
      higher efficiency than cell-derived virus. These data imply that the natural
      virus, whilst able to replicate on MDCK cells, is by no means the best fit for
      the MDCK receptor and variants with appropriate substitutions around the receptor
      binding site can readily displace the natural virus. Vaccine manufacturers who
      are investigating the use of tissue culture for vaccine production should
      minimize passage levels of cell-derived virus and beware of the displacement of
      the original virus with variants similar to those derived in eggs, which are
      often antigenically distinct.

PMID- 8578847
TI  - Specific secretory immune responses in the female genital tract following
      intranasal immunization with a recombinant adenovirus expressing glycoprotein B
      of herpes simplex virus.
AB  - Previously, we demonstrated that intranasal (i.n.) but not intraperitoneal (i.p.)
      immunization with a recombinant adenovirus vector expressing glycoprotein B (gB)
      of herpes simplex virus type 1 (HSV-1) induced mucosal immune responses and
      conveyed long-term protection to mice against an i.n. challenge with heterologous
      HSV-2. We now show that i.n. immunization of female mice with this same vector,
      AdgB8, provides secretory and serum-derived humoral immune responses in the
      genital tract. Intranasal immunization induced anti-HSVgB IgA and IgG in vaginal
      washes of mice, whereas i.p. immunization only induced IgG, which appeared to be
      serum-derived. Interestingly, intravaginal (ivag) immunization with AdgB8
      resulted in little or no anti-HSVgB IgA and only low levels of specific IgG in
      vaginal washes. All three routes of inoculation induced gB-specific serum IgG and
      IgA; however, i.n. immunized mice demonstrated the highest level of serum anti
      HSVgB IgA. Additionally, ivag boosting with AdgB8 did not significantly alter the
      serum or vaginal wash antibody responses in i.n. or i.p. immunized mice. The IgG
      to IgA ratios of gB-specific and total antibody titres in the serum and vaginal
      washes of i.n. immunized mice indicated that the IgA in the vaginal washes was
      likely to be secretory. Furthermore, the titres of anti-HSVgB IgA relative to
      total IgA were higher in vaginal washes than sera, suggesting that the gB
      specific vaginal wash IgA present in i.n. immunized mice was locally produced.

PMID- 8578848
TI  - Expression of fragment C of tetanus toxin fused to a carboxyl-terminal fragment
      of diphtheria toxin in Salmonella typhi CVD 908 vaccine strain.
AB  - We report the expression of fragment C of tetanus toxin (FC) fused to the
      eukaryotic cell binding domain (the carboxyl-terminus) of diphtheria toxin (FC
      bDt fusion) in attenuated Salmonella typhi live vector vaccine strain CVD 908.
      The FC-bDt protein fusion was constructed using plasmid pTETnir15 which carries
      the gene encoding FC under control of the nirB promoter (nirBP). The open reading
      frame for FC was modified to incorporate an in-frame glycine-proline hinge region
      and a set of four restriction sites at the 3' end of the FC gene. A 482 bp DNA
      fragment encoding the eukaryotic cell binding domain of diphtheria toxin was then
      inserted at the 3' end of the modified FC gene to create an in-frame FC-bDt
      fusion gene. The resulting plasmid, pOG215, was able to express the FC-bDt fusion
      protein in both Escherichia coli DH5a and S. typhi CVD 908, as evidenced by
      Western immunoblots using anti-FC and anti-C-terminal diphtheria toxin monoclonal
      antibodies. Maximum expression of the FC-bDt fusion protein was achieved by
      growing CVD 908(pOG215) at the low oxidation-reduction potential of
      thioglycollate broth, i.e. in conditions that activate nirBP and drive
      transcription of the FC-bDt fusion gene. Whereas maximum expression of FC alone
      was also observed using thioglycollate broth, expression of bDt alone was
      unsuccessful using a variety of growth conditions. FC fusions constitute one
      strategy to "rescue" expression of proteins which are otherwise difficult to
      express.

PMID- 8578849
TI  - Structure and immunogenicity of experimental foot-and-mouth disease and
      poliomyelitis vaccines.
AB  - The physico-chemical properties and immunogenicity of experimental vaccines
      against foot-and-mouth disease (FMD) and poliomyelitis, prepared by treatment of
      the viruses with N-acetylethyleneimine (AEI), formaldehyde or neutral red, have
      been studied. None of these reagents affects the rate of sedimentation of the
      particles or their reaction with antibody against the major immunogenic sites.
      FMD vaccines prepared by inactivation with AEI or neutral red, behaved like the
      untreated virus, in that they were disrupted on lowering the pH below 7. The RNA
      of the AEI-inactivated virus was degraded into slowly sedimenting molecules.
      Unlike AEI-inactivated virus, from which all the RNA could be extracted with
      phenol-SDS, the recovery from the neutral red inactivated virus was variable and
      was sometimes as low as 40%; this RNA gave a heterogenous profile in sucrose
      gradients. The capsid proteins in the AEI preparation migrated in SDS-PAGE to the
      same positions as those of untreated virus, but in the neutral red preparation
      there was evidence of cross-linking. In contrast, the formaldehyde-inactivated
      vaccine was stable below pH 7 and the RNA could not be released by extraction
      with phenol-SDS at pH 5, because the capsid proteins had become cross-linked
      and/or linked to the RNA. As with foot-and-mouth disease virus (FMDV), poliovirus
      which had been inactivated with formaldehyde did not release its RNA on
      extraction with phenol-SDS and the capsid proteins were also cross-linked.
      Surprisingly, although AEI cleaved the viral RNA slowly in situ, the virus was no
      longer infectious after 6 h. Neutral red did not reduce the infectivity of the
      virus. All of the preparations gave similar levels of neutralizing antibody after
      a single inoculation. The high levels obtained with the formaldehyde-inactivated
      vaccines have implications for the processing of fixed particles by the antigen
      presenting cells.

PMID- 8578850
TI  - Measles, mumps, and rubella antibodies in children 5-6 years after immunization:
      effect of vaccine type and age at vaccination.
AB  - The levels of antibody against measles, mumps, and rubella were determined at 5-6
      years postimmunization in 468 children vaccinated with two different trivalent
      vaccines. The proportions of children without detectable antibody levels were 12
      and 3.6% for measles (p < 0.001), 14.9 and 7% for mumps (p = 0.006), and 3.3 and
      3.1% for rubella (p = 0.88), respectively, in MMR II and Trivirix recipients. A
      higher proportion of those vaccinated at younger ages had undetectable or low
      levels of measles antibody. These data indicate that a large proportion of
      children vaccinated under routine conditions do not have detectable measles and
      mumps antibody.

PMID- 8578851
TI  - Persistence of anti-mumps virus antibodies after a two-dose MMR vaccination. A
      nine-year follow-up.
AB  - A two-dose vaccination program against measles, mumps, and rubella (MMR) viruses
      was started in Finland in 1982. In this program the trivalent MMR-II vaccine
      (MSD, USA) was offered to children at the ages of 14-18 months and 6 years
      followed by revaccination 4-5 years later. The vaccination coverage has been high
      (97%) and MMR infections have practically been eliminated in the Finnish
      population. In a serological follow-up program sequential serum samples were
      obtained from 254 children (127 14-18-month-old vaccinees and 127 6-year-old
      vaccinees) during a 9-year follow-up period. Anti-mumps virus antibody titers
      were determined by enzyme immunoassay using purified whole mumps viruses as the
      antigen. In seronegative (n = 120) 14-18-month-old vaccinees the seroconversion
      rate was 86% (geometric mean titer 1/1670 +/- 1/270). The antibody levels fell
      rapidly (significance p < 0.01) within the first year of follow-up (mean titer
      1/1080 +/- 1/190), but remained relatively stable in subsequent years. After
      revaccination the seropositivity rate was 95% (mean titer 1/2310 +/- 1/260) and
      declined more slowly thereafter to 86% (mean titer 1/1510 +/- 1/210) at year 9 of
      follow-up. The mean antibody titer was significantly (p < 0.05) higher 4 years
      after the second MMR vaccination when compared with the corresponding time point
      after the first vaccination. In 6-year-old seronegative vaccinees the increase
      and decay of anti-mumps virus antibodies after the first MMR vaccination was
      similar to that seen in the group of younger vaccinees. A two-dose MMR
      vaccination protocol resulted in a high mumps immunity level in the vaccinated
      population.

PMID- 8578852
TI  - New advances in vaccine technologies and applications. 13-15 February 1995,
      Bethesda, Maryland, USA.

PMID- 8578853
TI  - Nucleocapsid- and virus-like particles assemble in cells infected with
      recombinant baculoviruses or vaccinia viruses expressing the M and the S segments
      of Hantaan virus.
AB  - The formation of Hantaan (HTN) virus nucleocapsid-like structures (NLS) or virus
      like particles (VLP) from expressed gene products was investigated in two
      eukaryotic systems. Baculovirus expression of the HTN virus small segment (S),
      which encodes the viral nucleocapsid protein, resulted in assembly of NLS inside
      infected insect cells. The NLS and authentic ribonucleocapsids, prepared by
      detergent disruption of HTN virions, had similar sedimentation characteristics
      and morphologies, and were recognized by HTN virus N-specific antibodies. Co
      expression of S and the medium segment (M), which encodes the two viral envelope
      glycoproteins (G1 and G2), did not efficiently generate VLP in the baculovirus
      insect cell system, but VLP were observed in lysates and supernatants of cells
      infected with a recombinant vaccinia virus co-expressing HTN virus M and S. The
      VLP sedimented in sucrose to densities consistent with HTN virions, and some of
      them bore a striking resemblance to Hantaan virions when examined by
      immunoelectron microscopy.

PMID- 8578854
TI  - Genotypic variation in coxsackievirus B5 isolates from three different outbreaks
      in the United States.
AB  - Genomic sequences in VP1/2A and 5'-non-coding region of 10 isolates of
      Coxsackievirus B5 from three outbreaks were compared with published sequences of
      another Coxsackievirus B5, swine vesicular disease virus, Coxsackievirus B1,
      Coxsackievirus B3, and Coxsackievirus B4. Isolates of Coxsackievirus B5 from the
      same outbreak showed close relations, not exceeding 7.2% in nucleotide
      differences. Differences were greater between isolates from different outbreaks,
      varying between 8.4 and 16%. We have also shown that Coxsackie B5 viruses from an
      outbreak in 1967 are more similar to viruses from an outbreak in 1983 than to the
      viruses isolated from an intervening outbreak in 1972. The sequence comparison of
      Coxsackievirus B5 isolates with other Coxsackie B viruses and swine vesicular
      study, cDNA synthesis, polymerase chain reaction, and sequencing, are suitable
      for rapid Coxsackie B virus detection and identification of genotypic relations
      between viruses originating from different outbreaks.

PMID- 8578855
TI  - Hepatitis C virus genotyping by means of 5'-UR/core line probe assays and
      molecular analysis of untypeable samples.
AB  - To test the theoretical possibility of 5'-UR mistyping between hepatitis C virus
      subtypes 1a and 1b, we combined a 5'-UR/Core line probe assay (LiPA) with a
      nested PCR system and retested 183 sera, previously genotyped as type 1a or 1b
      and originating mainly from Western Europe. Eight percent of these were found to
      be wrongly subtyped. Based on this method, 3 additional subtypes of type 1 were
      discovered (1d-1f). Randomly selected European type 2 sera (n = 18) were tested
      with a similar type 2 5'-UR/Core LiPA. They were unexpectedly found to belong to
      subtype 2c in the majority of cases. Among serum samples originating from South
      East Asia, several additional genotypes (7a, 7c, 7d, and 9a) were detected which
      had 5'-UR sequence motifs indistinguishable from genotype 1. Based on 13,203
      pairwise comparisons in the 340-bp NS5B region, classification into types,
      subtypes, and isolates was obtained in 99.8% of all cases by using the
      phylogenetic border value of 0.328 for subtypes/types and 0.127 for
      isolates/subtypes; and evidence for a 10th major type of HCV was provided.
      Combination of all available HCV sequence data from the 447-bp Core/E1 region and
      the NS5B 340-bp and 222-bp regions provided evidence for the existence of 10
      types, including 50 subtypes. Previously, extensive studies involving genotypes
      1a, 1b, 2a, and 2b indicated the importance of HCV subtyping in interferon
      treatment and progression of chronic liver disease. The herein described
      expansion in the number of HCV types and subtypes should help improve diagnosis,
      treatment and possibly prophylaxis of hepatitis C liver disease.

PMID- 8578856
TI  - Molecular epizootiology and evolution of the glycoprotein and non-virion protein
      genes of infectious hematopoietic necrosis virus, a fish rhabdovirus.
AB  - Infectious hematopoietic necrosis virus (IHNV) causes a highly lethal,
      economically important disease of salmon and trout. The virus is enzootic
      throughout western North America, and has been spread to Asia and Europe. The
      nucleotide sequences of the glycoprotein (G) and non-virion (NV) genes of 12
      diverse IHNV isolates were determined in order to examine the molecular
      epizootiology of IHN, the primary structure and conservation of NV, and the
      evolution of the virus. The G and NV genes and their encoded proteins were highly
      conserved, with a maximum pairwise nucleotide divergence of 3.6 and 4.4%, and
      amino acid divergence of 3.7 and 6.2%, respectively. Conservation of NV protein
      sequence (111 amino acids in length) confirms that the protein is functional and
      plays an important role in virus replication. The phylogenetic relationship of
      viruses was found to correlate with the geographic origin of virus isolates
      rather than with host species or time of isolation. These data are consistent
      with stable maintenance of virus in enzootic foci. Two main IHNV genetic lineages
      were identified; one in the Columbia River Basin (Oregon, Washington and Idaho),
      the other in the Sacramento River Basin (California). The first major IHNV
      outbreak in chinook salmon in 1973 in the Columbia River was genetically linked
      to importation of virus-infected fish eggs from the Sacramento River where
      outbreaks in chinook salmon are common. However, the introduced virus apparently
      did not persist, subsequent virus outbreaks in Columbia River chinook salmon
      being associated with Columbia River genetic lineages. In general, virus
      monoclonal antibody reactivity profiles and phylogenetic relationships correlated
      well.

PMID- 8578857
TI  - The complete genome structure and phylogenetic relationship of infectious
      hematopoietic necrosis virus.
AB  - Infectious hematopoietic necrosis virus (IHNV), a member of the family
      Rhabdoviridae, causes a severe disease with high mortality in salmonid fish. The
      nucleotide sequence (11,131 bases) of the entire genome was determined for the
      pathogenic WRAC strain of IHNV from southern Idaho. This allowed detailed
      analysis of all 6 genes, the deduced amino acid sequences of their encoded
      proteins, and important control motifs including leader, trailer and gene
      junction regions. Sequence analysis revealed that the 6 virus genes are located
      along the genome in the 3' to 5' order: nucleocapsid (N), polymerase-associated
      phosphoprotein (P or M1), matrix protein (M or M2), surface glycoprotein (G), a
      unique non-virion protein (NV) and virus polymerase (L). The IHNV genome RNA was
      found to have highly complementary termini (15 of 16 nucleotides). The gene
      junction regions display the highly conserved sequence UCURUC(U)7RCCGUG(N)4CACR
      (in the vRNA sense), which includes the typical rhabdovirus transcription
      termination/polyadenylation signal and a novel putative transcription initiation
      signal. Phylogenetic analysis of M, G and L protein sequences allowed insights
      into the evolutionary and taxonomic relationship of rhabdoviruses of fish
      relative to those of insects or mammals, and a broader sense of the relationship
      of non-segmented negative-strand RNA viruses. Based on these data, a new genus,
      piscivirus, is proposed which will initially contain IHNV, viral hemorrhagic
      septicemia virus and Hirame rhabdovirus.

PMID- 8578858
TI  - Molecular characterisation of UK isolates of barley yellow mosaic bymovirus.
AB  - Several isolates of barley yellow mosaic virus (BaYMV) from different sites in
      the UK, including some that were virulent on European resistant winter barley
      cultivars (resistance-breaking strain: BaYMV-2) and some that were not, were
      examined by RT-PCR, restriction mapping and sequencing of selected parts of the
      virus genome. Nucleotide and predicted amino acid sequences were determined for
      the 5'-terminal region, part of the NIa coding region and the coat protein coding
      region on RNA 1 and an area at the N-terminus of the 70-kDa protein coding region
      on RNA 2. The sequences differed from those previously reported for a BaYMV
      isolate from Japan and for two German isolates, one of which was of the BaYMV-2
      strain. There were no strain-specific amino acid differences and the few, non
      consecutive, nucleotide differences detected were probably not significant and
      were insufficient to develop a rapid diagnostic test to distinguish BaYMV-2 from
      other isolates. Restriction mapping of RNA 2 cDNA again showed no consistent
      strain-related differences. The differences previously reported between the two
      German isolates are probably not strain-related.

PMID- 8578859
TI  - The use of African horse sickness virus NS3 protein, expressed in bacteria, as a
      marker to differentiate infected from vaccinated horses.
AB  - Segment 10 of the double-stranded RNA (dsRNA) genome from African horse sickness
      virus serotype 4 (AHSV-4) was cloned and sequenced. The sequence of the coding
      region showed a total length of 667 bp. Nucleotide comparisons showed a 95%
      sequence similarity between serotypes 4 and 9, and 76% between serotypes 4 and 3.
      cDNA clones containing the coding region were cloned in the vector pET3xb and
      expressed in Escherichia coli. The NS3 gene product was synthesised at very high
      level as an insoluble fusion protein. The recombinant protein was used in a
      differential ELISA to distinguish horses that were infected with AHSV-4 or
      vaccinated with live-modified virus from those vaccinated with a purified
      inactivated vaccine. The results obtained indicate that recombinant NS3 can
      indeed differentiate between infected and vaccinated animals implying that this
      recombinant could be developed as a diagnostic reagent, and it would allow the
      mobility of vaccinated horses. Thus, economical losses associated with this
      disease could be avoided.

PMID- 8578860
TI  - Preparation of monoclonal antibodies against Marek's disease virus serotype 1
      glycoprotein D expressed by a recombinant baculovirus.
AB  - A recombinant baculovirus, the genome of which contains DNA encoding Marek's
      disease virus serotype 1 (MDV1) homolog of glycoprotein D (gD) of herpes simplex
      virus under the polyhedrin promoter was constructed and designated rAcMDV1gD.
      Five monoclonal antibodies (MAbs) which recognize the MDV1 homolog of gD (MDV1
      gD) in Spodoptera frugiperda cells infected with rAcMDV1gD were prepared. The
      MAbs reacted with proteins ranging from 52 to 49 kDa in rAcMDV1gD-infected cell
      lysates by immunoblot analysis. These molecular weights were coincident with
      molecular weights predicted from the open reading frame of MDV1 gD. By ELISA
      additivity test, the 5 MAbs were divided into 3 groups which seemed to recognize
      3 different epitopes. In addition, all of the 5 MAbs were reactive with chick
      embryo fibroblasts (CEFs) expressing MDV1 gD. The MAbs are considered to be
      useful to study the role of MDV1 gD in MDV1 infection.

PMID- 8578861
TI  - A nested polymerase chain reaction assay to differentiate pestiviruses.
AB  - Viruses that comprise the Pestivirus genus cause significant losses to the
      livestock industry. Based on sequence analysis, currently 4 distinct genotypes
      are identified of which 3 infect cattle and sheep. Distinguishing between bovine
      and ovine isolates by serological tests has often been difficult because of a
      high degree of cross reactivity. In this study, a nested polymerase chain
      reaction (PCR) assay was developed to identify and distinguish between bovine
      viral diarrhea virus (BVDV) type I, BVDV type II, as well as border disease virus
      (BDV) genotypes. Consensus oligonucleotide primers were designed to amplify a 826
      bp product from any of the 3 pestivirus types in a reverse transcription-PCR (RT
      PCR). This product was subjected to a second round of nested PCR with type
      specific primers which yielded DNA products of unique size characteristic for
      each pestivirus genotype. Using this assay, we were able to rapidly characterize
      several viral isolates and determine that all 3 genotypes can be found among
      ovine isolates.

PMID- 8578862
TI  - Protein interactions entered into by the measles virus P, V, and C proteins.
AB  - Measles virus (MV) expresses at least 3 proteins from the phosphoprotein (P)
      cistron. Alternative translation initiation directs synthesis of the C protein
      from the +1 reading frame, while so-called RNA editing generates a second
      population of mRNAs which express the V protein from the -1 reading frame which
      lies within and overlaps the larger P reading frame. While the P protein has been
      demonstrated to be an essential cofactor for the L protein in the formation of
      active transcriptase complexes, the functions of the V and C proteins remain
      unknown. In order to investigate these functions, we have expressed the MV P, V
      and C proteins as GST fusions in E. coli for affinity purification and use in an
      in vitro binding assay with other viral and cellular proteins. The P protein was
      found to interact with L, NP, and with itself. These interactions were mapped to
      the carboxy-terminal half of the protein which is absent in the V protein. In
      contrast, both the V and C proteins failed to interact with any other viral
      proteins, but were each found to interact specifically with one or more cellular
      proteins. Appropriate aspects of these results were confirmed in vivo using the
      yeast two-hybrid system. These observations suggest that the V and C proteins may
      be involved in modulation of the host cellular environment within MV-infected
      cells. Such activity would be distinct from their previously proposed role in the
      possible down-regulation of virus-specific RNA transcription and replication.

PMID- 8578863
TI  - Selective loss of unmethylated segments of integrated Ad12 genomes in revertants
      of the adenovirus type 12-transformed cell line T637.
AB  - We have studied the stability of integrated adenovirus type 12 (Ad12) DNA
      sequences and the relation of foreign DNA persistence to the state of methylation
      of this DNA. In the Ad12-transformed hamster cell line T637, multiple copies of
      Ad12 DNA are chromosomally integrated. Some of these integrated viral genomes are
      rearranged in that internal parts of the viral DNA have become juxtaposed to its
      left terminus. Fluorescent in situ hybridization analyses demonstrate that the
      Ad12 DNA in cell line T637 and in some of its revertants is located at one site
      on one of the hamster chromosomes. Major portions of the integrated viral genomes
      in cell line T637 have become extensively de novo methylated in specific
      patterns. Most of the rearranged Ad12 DNA sequences in the T637 genome are un- or
      hypomethylated. In the morphological revertants of the Ad12-transformed hamster
      cell line T637, the majority of the integrated Ad12 genomes has been lost.
      Surprisingly, we have found that the un- or hypomethylated rearranged viral
      sequences have been selectively lost, in contrast to some of the methylated
      sequences that are stably retained.

PMID- 8578864
TI  - Characterization of a murine-human chimeric antibody with specificity for the pre
      S2 surface antigen of hepatitis B virus expressed in baculovirus-infected insect
      cells.
AB  - We have produced and characterized a murine-human chimeric antibody with
      specificity for the pre-S2 surface antigen of hepatitis B virus (HBV) in
      baculovirus-infected insect cells. Recombinant baculovirus carrying the cDNA
      coding for the heavy or light chain of the chimeric antibody was constructed and
      co-infected into insect cells. The chimeric antibody (BV-S2) expressed in the
      cells was purified by an affinity chromatography on Protein A-Sepharose 4B column
      and characterized by N-terminal amino acid sequencing, affinity determination for
      pre-S2 peptide, endoglycosidase digestion and Clq binding assay, which were then
      compared with those of the chimeric antibody H69K that has the same amino acid
      sequence as BV-S2, but produced from transfected murine myeloma cells. The N
      linked glycosylation of the BV-S2 antibody was also analyzed by culturing the
      baculovirus-infected cells in the presence of tunicamycin. The results showed
      that the BV-S2 was secreted following correct removal of the leader peptides,
      contained N-linked carbohydrate at the heavy chain, and had the same binding
      affinity and Clq binding ability as H69K, suggesting that the BV-S2 chimeric
      antibody is functional and thus may be useful in the prevention of HBV infection.

PMID- 8578865
TI  - Genetic characterization of a human isolate of Puumala hantavirus from France.
AB  - PUU90-13 is a strain of Puumala (PUU) virus (family Bunyaviridae: genus
      Hantavirus) isolated from a human in northeastern France (Rollin et al., 1995).
      This report describes the full-length sequences of the small (S) and medium (M)
      genomic RNAs of PUU90-13. The terminal sequences of both the S and M genomic RNAs
      were found to be conserved and imperfectly complementary. The S RNA of PUU90-13
      is 1847 nt in length and contains the nucleocapsid (N) protein gene and a
      potential overlapping open reading frame (ORF-2) previously described in other
      hantaviruses. Statistical analysis of the third base substitution frequency in
      the N ORFs of PUU90-13 and other PUU viruses suggests that the ORF-2 is
      functional. The M RNA is 3681 nt in length and encodes the glycoprotein
      precursor. Both genomic segments share the highest degree of nucleotide and amino
      acid sequence identity with PUUBerkel, a PUU virus from Germany. Phylogenetic
      analyses of sequences from both segments indicate that PUU90-13 occupies a
      distinct Western European PUU virus lineage that it shares with PUUBerkel. Both
      PUU90-13 and PUUBerkel lack a potential N-linked glycosylation site found on the
      G2 glycoprotein of other PUU viruses.

PMID- 8578866
TI  - Comparison of receptor-binding properties among influenza C virus isolates.
AB  - A total of 10 influenza C virus strains isolated recently in Yamagata City, Japan
      and shown to belong to the same lineage was compared for the ability to
      agglutinate chicken and mouse erythrocytes under various conditions.
      C/Yamagata/10/89 was unique in lacking the ability to agglutinate chicken
      erythrocytes at a temperature > or = 4 degrees C. This isolate also agglutinated
      native mouse erythrocytes only very inefficiently, although the high
      agglutination titer was obtained with the glutaraldehyde-fixed cells.
      Furthermore, it was found that C/Yamagata/4/88, unlike the other isolates,
      agglutinated erythrocytes from chickens to lower titers than those from mice,
      even when assayed at 0 degree C. Comparison of the deduced amino acid sequence of
      hemagglutinin-esterase among the 6 representative strains including two older
      isolates, C/Yamagata/26/81 and C/Nara/2/85, suggested that the failures of
      C/Yamagata/10/89 to agglutinate chicken erythrocytes at > or = 4 degrees C and
      unfixed mouse erythrocytes to high titers may be due to amino acid changes at
      residues 337 (Glu-->Lys) and 340 (Thr-->Tyr), respectively, and that a change at
      residue 347 (Leu-->Ser) may be responsible for the decreased ability of
      C/Yamagata/4/88 to agglutinate chicken erythrocytes.

PMID- 8578867
TI  - Characterization of monoclonal antibodies recognizing neurotropic Friend murine
      leukemia virus.
AB  - We isolated a replication-competent, neurotropic retrovirus (FrC6 virus) and its
      molecular clone A8 from the NB-tropic Friend murine leukemia virus (FLV) complex.
      For detection and characterization of the FrC6 and A8 viruses, monoclonal
      antibodies (MAbs) against the FLV complex were established. Thirty MAbs, each of
      which reacted with the FLV-producing cell line, were tested for potential
      neutralizing activities; only two MAbs inhibited the proliferation of the A8
      virus. These two MAbs were ineffective or had very weak neutralizing activities
      toward the non-neurotropic FLV strain clone 57 virus. Further characterization of
      MAbs by immunoprecipitation revealed that 4 MAbs recognized the envelope protein
      of the A8 virus. Two of these 4 MAbs recognized the surface glycoprotein gp70,
      requiring the conformational epitope of the virus for this recognition, while the
      other two MAbs, which were reactive with the transmembrane protein p15E, were
      conformation-independent. Both of the MAbs against gp70 distinguished
      neuropathogenic and non-neuropathogenic viruses to some extent, through
      neutralizing activity or binding activity detected by immunoprecipitation,
      whereas the two MAbs against p15E reacted with the viruses in a similar manner.
      Furthermore, one of the MAbs distinguished the viral antigen in the wall of the
      vacuolation that composes the spongiotic lesion induced by FrC6 viral infection
      of the brain.

PMID- 8578868
TI  - Characterization of monoclonal antibodies recognizing amino- and carboxy-terminal
      epitopes of the herpes simplex virus UL42 protein.
AB  - A panel of monoclonal antibodies (MAbs) directed against the herpes simplex virus
      type 1 (HSV-1) DNA polymerase (Pol) accessory protein, UL42, was developed and
      characterized. Thirteen different MAbs were isolated which exhibited varied
      affinities for the protein. All MAbs reacted with UL42 in ELISA, Western blot and
      immunoprecipitation analyses. Competitive ELISA was used to show that 6 different
      epitopes within UL42 were recognized by the MAbs. Immunoprecipitation of amino-
      and carboxy-terminal truncations of UL42 mapped the epitopes to regions
      containing amino acids 1-10, 10-108, 338-402, 402-460, and 460-477. All but one
      of these epitopes were outside the minimal active portion of the protein
      previously mapped to amino acids 20-315. None of these MAbs, alone or in
      combination, specifically neutralized the ability of UL42 to stimulate Pol
      activity in vitro. These results are consistent with structure-function studies
      that showed that N- and C-terminal regions of the UL42 protein, those recognized
      by the MAbs, are not involved in UL42 function in vitro.

PMID- 8578869
TI  - Retroviral vector-transduced cells expressing the core polyprotein induce feline
      immunodeficiency virus-specific cytotoxic T-lymphocytes from infected cats.
AB  - The core polyprotein of feline immunodeficiency virus (FIV) was expressed in
      primary feline T-lymphocytes using a retroviral vector. These cells were used as
      antigen-presenting stimulator cells (APSC) for the in vitro induction of
      cytotoxic T-lymphocytes (CTL) from feline peripheral blood mononuclear cells
      (PBMC). CTL from 4 cats chronically infected with the Petaluma strain of FIV
      specifically lysed autologous FIV-infected targets in an MHC-restricted manner.
      The CD8 phenotype of more than 70% of the induced effector cells (97% for cells
      from one cat) was consistent with MHC class I-restricted cytotoxicity. In
      addition, it was possible to detect low levels of core polyprotein-specific lysis
      from effector cells of two of the FIV-infected cats. When observed, the level of
      lysis, measured as a percentage of specific 111In release, was lower for the
      transgenic gag-expressing targets than for FIV-infected targets. The difference
      in killing may reflect the low level of core CTL were not detected in either PBMC
      stimulated with cells transduced by a retroviral vector without the FIV gag
      sequence or PBMC from an uninfected cat stimulated with autologous transgenic
      APSC. The detection of FIV-specific CTL from infected cats following stimulation
      with transgenic APSC suggests a role for retroviral vectors in determining CTL
      specific for individual lentiviral proteins in protective immunity.

PMID- 8578870
TI  - Monitoring systems to evaluate the quality of perinatal care.

PMID- 8578871
TI  - The impact of assisted reproduction on perinatal health care.

PMID- 8578872
TI  - Fetal origins of adult hypertension.

PMID- 8578873
TI  - The crucial role of definition in perinatal epidemiology.

PMID- 8578874
TI  - The cost of neonatal care: reviewing the evidence.

PMID- 8578875
TI  - Cost of neonatal care in the referral hospital of Lausanne (Centre Hospitalier
      Universitaire Vaudois, CHUV), Switzerland.

PMID- 8578876
TI  - [Costs and cost coverage of the neonatology department, University Women's
      Hospital and canton Women's Hospital, Bern].

PMID- 8578877
TI  - [Cost of the neonatology clinic of the Zurich University Hospital].

PMID- 8578878
TI  - [Output of disability insurance in the field of neonatology].

PMID- 8578879
TI  - [Cost and its compensation in neonatology: brief commentary].

PMID- 8578880
TI  - Geographic distribution of livebirths < 2000 g in Switzerland.

PMID- 8578881
TI  - The Swiss Paediatric Surveillance Unit (SPSU).

PMID- 8578882
TI  - Frequency and duration of breast-feeding in Switzerland.

PMID- 8578883
TI  - [ANCA: vasculitis research on the upswing].

PMID- 8578884
TI  - [ANCA-associated vasculitis (Wegener's granulomatosis, Churg-Strauss syndrome,
      microscopic polyangiitis). 1. Systemic aspects, pathogenesis and clinical
      aspects].
AB  - ANCA-associated vasculitides (AAV) include primary vasculitides that affect
      predominantly small vessels such as Wegener's Granulomatosis (WG), Microscopic
      Polyangiitis (MPA) and Churg-Strauss Syndrome (CSS). The former is closely
      associated with cANCA, induced by proteinase 3, MPA is characterized by pANCA
      with MPO specificity and the latter, CSS, can--to a far lesser extent--be
      associated with, either c- or pANCA. All AAV have in common (as opposed to immune
      complex-vasculitides) that they occur without complement consumption and show
      histologically no deposition of immune complexes (pauci-immune vasculitis).
      Clinically, the AAV show quite variable courses. The mostly clinically rather
      inapparent initial phase, which is typically granulomatous in WG and CSS, is
      mostly followed by a potentially life-threatening phase of full blown generalized
      systemic vasculitis. Frequently, rheumatic complaints are the initial symptom.
      The characteristic clinical features in the full blown generalized vasculitis are
      mostly found in the upper respiratory tract, the lung and/or the kidney.
      Subsequently, the clinical pictures of AAV will be described, especially taking
      into consideration the rheumatic manifestations as early symptoms. Furthermore,
      pathodynamics and differential diagnoses of AAV will be regarded.

PMID- 8578885
TI  - [ANCA-associated vasculitis (Wegener's granulomatosis, Churg-Strauss syndrome,
      microscopic polyangiitis). 2. Diagnostic procedure].
AB  - The ANCA-associated vasculitides (Wegener's granulomatosis, Churg-Strauss
      syndrome, microscopic polyangiitis) are characterized by a broad spectrum of
      clinical manifestations and a highly variable clinical course. Due to greatly
      improved diagnostic techniques the number of newly diagnosed cases has increased
      rapidly within the past few years. This facilitated more individualized treatment
      and led to the concept of stage-adapted treatment. Immunodiagnostic parameters
      are being utilized increasingly to supplement clinical and radiological findings.
      Inflammatory lesions are visualized by, for example, e.g. rhinoscopy, sinoscopy,
      and bronchoscopy or by radiological techniques including cranial and skeletal
      muscle magnetic resonance imaging, pulmonary high-resolution computed tomography,
      and digital subtraction angiography. These techniques not only serve to detect
      the extent of tissue and organ involvement, but also to direct bioptic
      procedures. Conventional histopathology must be supplemented by immunohistology
      in order to distinguish between the "immune complex vasculitides" and the ANCA
      associated "pauci-immune vasculitides".

PMID- 8578887
TI  - [Coping with the illness by patients with chronic polyarthritis. Forms of coping
      and therapeutic implications].
AB  - In rheumatoid arthritis, coping exerts a major influence on the feelings and the
      compliance of a patient. This signifies its great clinical relevance. This study
      presents data of 40 patients using a questionnaire for assessing their ways of
      coping. The main coping strategies proved to be the search for more information
      and ways to get cognitive control over the threat imposed by the disease. The
      individual strategies were not influenced by somatic parameters. Unexpectedly,
      the duration of disease was tightly correlated to a more intensive approach for
      gaining information. The results have a major influence on the way of treating
      patients with RA. They open up new therapeutical regimens for the patient/doctor
      relationship, including patient oriented seminars and various psychological
      therapies.

PMID- 8578886
TI  - [ANCA-associated vasculitis (Wegener's granulomatosis, Churg-Strauss syndrome,
      microscopic polyangiitis). 3. Therapeutic procedure].
AB  - Recent studies on the long-term clinical course of ANCA-associated vasculitides
      have revealed considerable variation in the clinical severity of the disease. The
      most effective standard therapy (i.e., daily cyclophosphamide + prednisolone,
      "FAUCI-scheme") is associated with high treatment-related morbidity and mortality
      as well as a high incidence of relapse. On the other hand, less toxic therapeutic
      strategies (e.g., monthly bolus of cyclophosphamide or weekly low-dose
      methotrexate) are being pursued with remarkable success in non-life threatening
      disease. Intractable cases (under daily cyclophosphamide + prednisolone) may
      profit from additional high dose IVIG therapy or from monoclonal antibodies
      against CD4 and CDw52 molecules. Plasmapheresis can be effective in combination
      with the standard therapy in dialysis patients with necrotizing
      glomerulonephritis (in Wegener's granulomatosis or microscopic polyarteritis). On
      the other hand, Wegener's granulomatosis restricted to the upper and/or lower
      respiratory tract ("Initial WG") responds to trimethoprimsulfamethoxazole. In
      future, therefore, an individualized strategy adapted to extension and activity
      has to be developed for the treatment of each patient with ANCA-associated
      vasculitis.

PMID- 8578888
TI  - [Coping with stress and rheumatoid factor--a comparative study].
AB  - Forty-six seropositive female RA patients were compared to 28 seronegative female
      RA patients and 51 healthy women using the stress-coping questionnaire of Janke
      et al. (9). In comparison to healthy controls, patients with RA exhibit a stress
      coping behavior characterized by more cognitive coping mechanisms, less self
      accusation, less aggression, and less use of alcohol or pharmaca. They too use
      more substitutive gratification, a strategy which is used by seropositive
      patients even more than by seronegative patients. Further, compared to healthy
      controls and seronegative patients, seropositive patients describe more attempts
      to control their reactions in stress situations.

PMID- 8578889
TI  - [Virus-induced arthritis].

PMID- 8578890
TI  - [Virus-associated arthritis].
AB  - From the about 400 virus species known to cause illness in man, only a small but
      growing list of representatives are able to induce arthritis. Although virus
      associated arthritides are mostly of acute and short-living type, some patients
      develop long-lasting or even chronic joint inflammation. The viral or host
      factors which contribute to chronicity or severity of viral joint disease are not
      known. However, the study of patients with long-lasting viral arthritis and of
      patients with idiopathic chronic arthritides may allow unique insights into the
      potential role of viruses in the pathogenesis of inflammatory joint disease.

PMID- 8578891
TI  - [Cutaneous side-effects of nonsteroidal anti-inflammatory drugs (NSAID)].
AB  - NSAID are able to induce cutaneous side-effects by both systematical and topical
      application. Nearly all kinds of exanthema are possible by any type of these
      drugs. However, particular substances are more likely to induce certain drug
      eruptions; aspirin and indometacine may induce urticarial reactions, whereas
      piroxicam can lead to phototoxic or photoallergic dermatitis. Contact dermatitis
      induced by topical NSAID is still rare but increasing. Ketoprofen and bufexamac
      were major contact allergens based on the number of reports, but local
      differences among different countries were observed. The diagnosis of drug
      reactions, especially in systemic drugs, remains a problem because reliable in
      vitro methods are not yet in use and skin test procedures do not work in most
      cases. Therefore, the case history is still the most useful tool in evaluating
      anamnestic allergic events. Prospective studies of drug compatibility as well as
      an improvement of side-effect reports are necessary to assess specific risks for
      several drugs.

PMID- 8578892
TI  - [Methotrexate therapy of polymyalgia rheumatica].
AB  - Twenty-seven patients with polymyalgia rheumatica were treated with methotrexate.
      In comparison with 295 patients with other inflammatory rheumatic diseases under
      methotrexate therapy, a favorable rate of therapeutic effect and a low rate of
      side-effects could be observed. Remissions appeared in the mean after 6 months (1
      24 months). Therapeutic failures (1/27) or side-effects inducing breaking off the
      therapy (2/27) were rare. Methotrexate seems to be a useful possibility to
      supplement the corticosteroid therapy of polymyalgia rheumatica.

PMID- 8578893
TI  - [Lumbar epidural lipomatosis].
AB  - Spinal epidural lipomatosis is a pathological accommodation of fat tissue in the
      spinal canal. It seems to be a disease entity, which, though rare, has recently
      been diagnosed more frequently and can be accompanied by neurological deficits.
      The thoracic spinal canal is the preferred localization. Eighteen cases of
      symptomatic lumbar epidural lipomatosis have been described in the literature. We
      are reporting on our experience with another 8 patients. Three of these patients
      presented with the typical signs of spinal nerve irritation. In these cases
      epidural lipomatosis was associated with a small disk herniation without direct
      contact to the spinal nerve. Another 5 patients showed the clinical picture of a
      spinal claudication. In all 5 patients, there was a concentric compression of the
      thecal sac by epidural fat. In one patient, the cause of the lipomatosis was
      assumed to be long-term steroid therapy following kidney transplantation. Four
      patients suffered from extreme obesity. No cause for lipomatosis could be found
      in 3 patients. A microdiskektomy was performed in the 3 patients with the
      associated disk herniation; the remaining patients were treated conservatively.
      In 6/8 patients (3x surgery/3x diet), an "excellent" or "good" clinical result
      could be achieved after 1 year. Two patients had a "satisfactory" result. Lumbar
      epidural lipomatosis can be treated conservatively in cases with only mild
      neurological dysfunctions and known cause (e.g. obesity, steroid therapy). The
      surgical removal of associated disk herniation proved to be sufficient in cases
      described in this paper.

PMID- 8578895
TI  - Cardiovascular, respiratory and metabolic effects of interval training at VLA4.
AB  - The purpose of this study was to determine if training with short intervals at
      the velocity producing a lactate level of 4 mmol/l (VLA4) is sufficient to induce
      adaptations and better exercise tolerance. Five Standardbred mares (4-8 years)
      were interval trained on a treadmill 3 days a week for 12 weeks and subsequently
      detrained for 4 weeks. Standardized exercise tests were performed before, during
      and after the training period and muscle biopsies were taken. Measurements were
      made of heart rate, oxygen consumption, stride frequency, blood volume and blood
      lactate. Plasma volume was reduced after 2 weeks of training but then increased
      to the approximate pre-training value throughout the remaining training and post
      training periods. No change was detected in the total cell volume whereas the
      total blood volume varied in consequence with the plasma volume variation. A
      significant reduction in heart rate response to exercise was seen after 4 weeks
      of training. VLA4 increased after 2 weeks of training and remained higher than
      the baseline value during the rest of the training period. Consequently, the
      blood lactate at 8 m/sec was decreased compared to baseline concentration after 8
      and 12 weeks of training. The post-training VLA4 did not differ significantly
      either from the end of training or from the pre-training value. Mass specific
      oxygen consumption (VO2-200/BW) at V200 increased with training and decreased
      with detraining. The respiratory quotient at a velocity of 8 m/sec decreased from
      1.18 +/- 0.02 before training to 1.07 +/- 0.02 (P < 0.05) at the end of training.
      No changes were found in muscle histo- or biochemical parameters. The results
      indicate that training at VLA4 is sufficient to cause adaptational changes in
      exercise tolerance related parameters.

PMID- 8578894
TI  - [Atypical course in (eosinophilic) fasciitis].
AB  - A 22-year old male patient developed--following a short phase of monarthritis-
      the symptoms of a symmetric, polysynoviatic, discrete erosive rheumatoid
      arthritis, thus fulfilling five of seven ACR criteria. Initially as well as
      persisting during the course of the disease the palpable swelling of synovitis
      showed a coarse character. The radiological progression at the hands during an
      interval of eight years being only minimal the loss of functions, up to
      contraction of joints (left hip) augmented considerably during that time. Neither
      rheumatoid factor or antinuclear antibodies nor evident eosinophilia or
      hypergammaglobulinaemia could be proved or verified. In 1994 muscle biopsy led to
      the diagnosis "fasciitis with low-graded eosinophilia". Anamnestic, clinical and
      radiological signs and data as well as the course of the disease and assessing of
      differential diagnoses are presented and discussed.

PMID- 8578896
TI  - Comparison of the kinetics of sodium meclofenamate versus meclofenamic acid after
      oral administration to sheep.
AB  - Meclofenamates are non-steroidal anti-inflammatory agents used in ruminants for
      the prevention and the treatment of anaphylactic processes. The objective of the
      present work was to study possible kinetic variations due to the chemical form of
      meclofenamates administered by the oral route to adult sheep. Six Rubia del Molar
      female sheep (2-3 years old, 47-57 kg) were used. Initially, an intravenous
      administration of sodium meclofenamate (2.2 mg/kg bwt) was given; the obtained
      kinetic results were in agreement with data from other authors. Oral
      administrations (20 mg/kg bwt) of sodium meclofenamate and meclofenamic acid were
      then given. When the reticular groove was opened, both drug forms showed a single
      meclofenamate plasma peak; t2max were 60.0 +/- 10.61 min and 127.50 +/- 22.5 min
      for the sodium and acid form, respectively. The elimination rate constants (beta)
      were not significantly different, but the absorption half-lives were (14.69 +/-
      3.21 min for the sodium form and 61.07 +/- 21.7 min for the acid form). The
      bioavailability was 48.6 +/- 4.3% for sodium meclofenamate and 65.1 +/- 2.8% for
      meclofenamic acid. Thus, the chemical form (sodium versus acid) alters the oral
      bioavailability and tmax of meclofenamates in adult sheep. These findings agree
      with the behaviour of meclofenamates in man.

PMID- 8578897
TI  - Round cell sarcomas of possible myelomonocytic origin localized at the lip of
      aged dogs.
AB  - Four round cell tumors, situated at the lip of dogs older than 4 years of age,
      which could not be further classified, were examined light and electron
      microscopically, immunocytochemically and in part functionally and
      cytochemically. Immunocytochemically they were positive for vimentin, but
      negative for cytokeratin, desmin, neurofilament, synaptophysin, S-100 protein,
      neuron specific enolase, lysozyme, IgG and a pan-T-cell marker. Cell lines were
      established from two malignant neoplasms. In vitro, neoplastic cells had
      morphological, functional and cytochemical properties of myelomonocytic cells. A
      tumor cell-specific polyclonal rabbit antiserum reacted immunocytochemically
      positive with primary and recurrent tumors and metastases of the original and the
      three other round cell tumors. Immunoblotting demonstrated a main band with
      approximately 65-75 kDa. All four tumors were present in aged dogs and
      metastasized. They most likely represent a distinct group of malignant tumors
      among the canine round cell tumors.

PMID- 8578898
TI  - Species specific pharmacokinetics of rolitetracycline.
AB  - Comparative studies on some selected pharmacokinetic parameters of
      rolitetracycline (effective antimicrobial activity levels) in sheep, pigs,
      rabbits, chickens and pigeons were carried out after intravenous administration
      of the drug at a dose of 5 mg/kg. The results revealed that a two-compartment
      open model was usually optimal. Interspecies differences in the rate (alpha) and
      the volume of distribution (Vda), the area under the serum concentration time
      curve (AUC) and the total body clearance (ClB) were small. The values of the
      elimination half-life (t1/2 beta) found in sheep, pigs, rabbits, chickens and
      pigeons were 1.51, 3.06, 2.18, 4.33 and 2.51 h respectively. These results and
      data in mice, rabbits and man taken from literature were analysed to determine
      any correlation to body mass (W). The log of the elimination half-life values
      (log t1/2 beta) of rolitetetracycline revealed a significant correlation with log
      values of (W) between animal species. This relationship was described by the
      equation t1/2 beta = 1.27.W0.29 (r = 0.93, P < 0.01, n = 5) for mammal species
      and t1/2 beta = 1.81.W0.24 (r = 0.78, P < 0.05, n = 7) for mammal and bird
      species.

PMID- 8578899
TI  - Detection of clenbuterol (Ventipulmin) in the horse.
AB  - An enzyme linked immunosorbent assay (ELISA) was developed to detect the beta 2
      agonist clenbuterol in equine blood and urine. The antiserum was raised in
      rabbits, employing clenbuterol-diazo-BSA as antigen. Clenbuterol-diazo
      horseradish peroxidase served as enzyme conjugate. The concentration of
      clenbuterol to decrease tracer binding by 50% (IC50 value) was found to be 27.50
      +/- 4.20 pg/well (1.37 ng/ml). The antibody cross-reacted with salbutamol (30%),
      terbutaline (14%) and cimaterol (1%). Horse serum was used directly to screen for
      clenbuterol, while urine was employed diluted. Positive screening results were
      confirmed by means of two independent HPLC systems combined with off-line
      detection by the clenbuterol-ELISA. Salbutamol served as internal standard to
      ascertain relative retention of the drug. The detection limit of clenbuterol in
      serum and urine amounted to 0.04 ng/ml. In addition, GC/MS technique was applied
      to detect clenbuterol in urine samples by a newly developed derivatization
      method. Confirmation of intravenously given clenbuterol in serum of horses
      treated with Ventipulmin (0.8 microgram clenbuterol.HCl/kg) was achieved by
      HPLC/ELISA up to 24 h, in urine up to 96 h. After oral administration, the beta 2
      agonist was detected in serum for 48 h and in urine for 75 h.

PMID- 8578900
TI  - [Evaluation of hypoxic conditions in calves using the erythrocyte density test
      (EDT)].
AB  - The erythrocyte density separation test (EDT) divides the red blood cells into
      two groups: younger (less dense) and older (more dense) erythrocytes. Using this
      test enables veterinarians to assess the erythropoiesis in calves on the basis of
      the percentage of less dense (younger) red blood cells. Anemic calves, as well as
      those with pneumonic infections show higher proportions of less dense red blood
      cells in the EDT than healthy ones. This testing procedure makes it possible to
      estimate the effects of an oxygen deficiency condition, such as hypoxemia,
      anemia, shock etc. on the peripheral tissues. So the EDT represents a valuable
      complement to existing hematological laboratory methods. Carrying out the EDT is
      very simple and suitable in routine clinical testing.

PMID- 8578901
TI  - Determination of lactate dehydrogenase activity and urea content in milk by dry
      chemistry.
AB  - Comparison of the new technique of dry chemistry (EKTACHEM 700-XR, Eastman Kodak
      Co., USA) with conventional wet chemistry (HITACHI 717, Boehringer Mannheim,
      Germany) for quantitations of lactate dehydrogenase activity and urea content in
      bovine milk resulted in correlation coefficients of more than 0.9 even when
      measuring fresh raw milk by dry chemistry.

PMID- 8578902
TI  - [Diagnostic and pathophysiological aspects of the determination of kidney
      function in animals].
AB  - Early diagnosis of loss in renal function (< 60-70%) is not possible either by
      resorting to the parameters of plasma urea and creatinine concentrations
      (responsive to functional loss by > 75% or by reference to urine concentration
      capacity (urine density: sensitive to concentrations > 60%). However, clearance
      techniques for determination of the glomerular filtration rate (GFR) have proved
      suitable for quantitative assessment of renal function. Endogenous creatinine
      clearance is one of the most common clinical approaches in GFR determination.
      Criticism of results obtainable from endogenous creatinine clearance appears to
      be justified by pharmacokinetic aspects of creatinine as an indicator, as well as
      by some of its analytical peculiarities. The tediousness of the procedure is
      another counterproductive aspect pertaining to large-scale use of endogenous
      creatinine clearance in veterinary medicine. Total blood-plasma clearance of
      exogenous creatinine (T-Clexo.Creatinine) would provide vets with an accurate
      (diagnostic validity) and practical method for carrying out clinical kidney
      function diagnostics. However, more research on a number of related issues will
      be required before the general introduction of the procedure.

PMID- 8578903
TI  - Chemical restraint by medetomidine-ketamine and its cardiopulmonary effects in
      pigs.
AB  - Chemical restraint induced by medetomidine-ketamine (M-K) combination was
      evaluated compared with that by xylazine-ketamine (X-K) in pigs. The duration of
      restraint by M-K was 49.4 +/- 13.5 min (mean +/- SD) and longer than that by X-K
      (34.6 +/- 17.2 min), but the difference was not significant. The effect of X-K
      was not stable, since one of five pigs was restrained only for 6 min. Both
      combinations produced muscle relaxation. The duration of muscle relaxation in M-K
      was 43.6 +/- 12.7 min and was significantly longer than that in X-K (21.0 +/-
      14.0 min). M-K combination had a slightly stimulative effect on the
      cardiovascular system, but scarcely changed the respiratory parameters. This
      limited effect on cardiopulmonary system was an advantage of M-K combination for
      chemical restraint in pigs. These results indicated that M-K combination is
      suitable for chemical restraint with prolonged muscle relaxation and has limited
      cardiopulmonary effects in pigs.

PMID- 8578904
TI  - Larval cyathostomiasis as a cause of death in two regularly dewormed horses.
AB  - Two horses were presented with complaints of chronic weight loss and subcutaneous
      oedema, one of them presenting diarrhoea. Both animals were grazed with other
      unaffected horses, all of them being regularly dewormed. Blood chemistry revealed
      hypoalbuminaemia and a low albumin-globulin ratio. Faecal egg counts were
      negative and no cyathostome larvae could be found in the faeces. Neither of these
      horses could be saved, despite intensive treatment. Postmortem examination
      revealed severe typhlitis and colitis due to numerous inhibited cyathostome
      larvae.

PMID- 8578905
TI  - Malformations of the vertebral bodies and the ribs associated to spinal
      dysraphism without spina bifida in a Pekingese dog.
AB  - A Pekingese dog with hemivertebrae, rib malformations and spinal cord dysraphism
      without spina bifida was presented. Two types of hemivertebrae were seen:
      bilateral and unilateral. Thoracic hemivertebrae were associated with fused ribs
      and rudimentary ribs. Spinal dysraphism consisted of polycavitary syringomyelia
      in the dorsal and lateral funiculi, hydromyelia and anomalies of the dorsal
      median septum and median fissure, associated to lumbar and sacral hemivertebrae.
      Cauda equina agenesia was also present. To conclude, the dog showed two
      malformations from different embryonic origins. Vertebral and rib malformations
      are of mesodermic origin and spinal dysraphism is of ectodermic origin. A
      possible common mechanism responsible for both anomalies is discussed.

PMID- 8578906
TI  - Effect of exercise on enzymatic activity in tracheal fluid and on intrapleural
      pressure difference in horses.
AB  - Seventeen trotters, eight healthy and nine with a mild respiratory disease,
      underwent a submaximal treadmill exercise. Heart rate, breathing frequency,
      intrapleural pressure difference (IP difference) as well as haematocrit and
      concentration of lactic acid in blood were monitored before exercise, during
      exercise and during recovery. The activities of beta-glucuronidase and plasmin,
      total proteolytic activity and trypsin inhibitory capacity were measured from the
      tracheal fluid before and after exercise. IP difference significantly increased
      during exercise and returned to normal values within 15 min in healthy horses.
      Differences in intrapleural pressure between healthy and diseased horses were not
      significant during exercise. Increase of the respiratory rate was monitored
      during recovery probably due to respiratory compensation of the lactic acidosis.
      Activities of beta-glucuronidase increased and activities of plasmin and trypsin
      inhibitory capacity decreased due to exercise. Most prominent changes were seen
      in the decrease of plasmin activity. The total proteolytic activity in the
      tracheal fluid before exercise correlated with the VLa4 values, indicating that a
      mild respiratory disease, which causes proteolysis in the respiratory tract,
      decreases performance capacity of the horse.

PMID- 8578907
TI  - Electromyography of the reticulum, abomasum and duodenum in dairy cows with left
      displacement of the abomasum.
AB  - Electromyographic (EMG) recordings of the reticulum, abomasal corpus, pyloric
      antrum and duodenum of six dairy cows with left displacement of the abomasum
      (LDA) were made in order to substantiate abomasal atony as a prerequisite to
      abomasal displacement. EMG recordings were made when LDA was present as well as
      when absent. Mean values were determined in five of six cows for the maximum peak
      or amplitude, mean peak values, peak-to-peak interval and count of the electrical
      response activity (ERA) for each 15 min segment of the waveform recordings.
      Segments containing phase III migrating myoelectric activity were not analysed.
      LDA positive periods were compared to LDA negative periods in each cow. The 6 h
      period (transition period) prior to the diagnosis of LDA was analysed separately.
      Paired t-tests were applied to group values with statistical significance
      established at the P = 0.05 level. There was a significant decrease in the ERA
      count during the LDA positive periods in the abomasal corpus (-1.40% to -7.88%, P
      = 0.0217) and in the pyloric antrum (-2.05% to -11.98%, P = 0.0430). A
      corresponding significant increase occurred in the peak-to-peak interval. During
      the transition period spike activity in the duodenum increased 0.5% to 48.31% (P
      = 0.0474) and the peak-to-peak interval was significantly decreased. No extended
      periods of atony were observed in the abomasum during this study.

PMID- 8578908
TI  - Expression of proliferating cell nuclear antigen in basal cell carcinomas and in
      squamous cell carcinomas of canine skin: correlation with mitotic index and
      histological features.
AB  - In this study we evaluated the behaviour of proliferating cell nuclear antigen
      labelling index (PCNA-LI), mitotic index (MI) and histological features in ten
      basal cell carcinomas (BCC) and ten squamous cell carcinomas (SCC) of canine
      skin. PCNA-LI ranged from 2.1% to 4.8% in SCC and from 0.1% to 2.0% in BCC
      samples. A significant statistical correlation, between PCNA-LI and MI could be
      demonstrated only in SCC, but not in BCC samples. Furthermore, PCNA-LI was also
      significantly and consistently greater in the three BCC of solid type and in
      poorly differentiated SCC. PCNA-LI may provide additional criterion in evaluating
      the intrinsic malignancy and growth potential of the above tumours.

PMID- 8578909
TI  - Course of pregnancy, steroid hormone levels and maturation process of placentomes
      after oestrone infusion in cows near term.
AB  - The present study was designed to examine the effect of systemic oestrone
      infusion on the course of late pregnancy and parturition, steroid hormone
      concentrations and maturation of placentomes in cows. Twelve pluriparous pregnant
      cows with known breeding dates were used in this experiment. Starting on day 267
      of pregnancy six cows (experimental group) received 20 mg oestrone daily (in four
      doses) infused into the vena jugularis until parturition. Six other cows infused
      with vehicle served as control. Concentrations of oestrone (E1), oestrone
      sulphate (E1S) and progesterone (P4) were measured by RIA, and after parturition
      placentomes were examined histologically. In experimental and control animals
      parturition occurred on days 276,9 +/- 1.8 and 277,2 +/- 1.1 of gestation,
      respectively. The concentrations of E1 in the treated group were higher (8-12
      ng/ml) than those in control animals (1-3 ng/ml), while the levels of E1S (8-14
      ng/ml) were similar for both groups. The concentrations of P4 in experimental and
      control cows were typical for late pregnancy (4-6 ng/ml), with a sharp drop of
      this hormone 1-2 days before calving. The histological pictures of placentomes
      obtained from both groups of animals were similar and maturation of the placenta
      was observed. These results suggest that the prepartal increase of oestrone in
      maternal plasma does not play a major role in the regulation of parturition and
      placental maturation.

PMID- 8578910
TI  - The sedative and analgesic effects of detomidine (Domosedan) in donkeys.
AB  - Detomidine (Domosedan) was administered to four groups of donkeys, using four
      different dosages (5, 10, 20 and 40 micrograms/kg bwt) intravenously. The drug
      provided adequate sedation at dosages of 5 and 10 micrograms/kg bwt. Sedation
      deepened only slightly by increasing the dose. Analgesia was considered good with
      a dose of 20 micrograms/kg, and 40 micrograms/kg provided a deep analgesia
      associated with a longer duration. No significant changes had been observed in
      haematocrit (PCV), haemoglobin content (Hb %), total red and white cell counts
      and differential leucocytic counts. It was concluded that detomidine is a
      valuable sedative and analgesic drug to be used in donkeys without any serious
      implications.

PMID- 8578911
TI  - [The status in wild and zoo birds of antibodies to selected agents relevant to
      domestic animals].
AB  - Serum samples from wild birds of 21 species were investigated for antibodies
      against a broad range of pathogenic microorganisms. Using routine diagnostic
      methods, antibodies against a choice of relevant viral and bacterial agents were
      detected. The epidemiology and the significance of infections in both wild birds
      and farm poultry are discussed.

PMID- 8578912
TI  - Phagocytosis of Streptococcus uberis by bovine mammary macrophages: opsonizing
      effect of bovine antiserum.
AB  - Five encapsulated and five non-encapsulated strains of Streptococcus uberis were
      tested for their ability to resist phagocytosis and intracellular killing by
      bovine mammary macrophages obtained during the non-lactating period. The
      percentage of phagocytosis and intracellular killing of encapsulated strains
      ranged from 43 to 51 and from 25 to 40, respectively. By contrast, the percentage
      of phagocytosis and intracellular killing of non-encapsulated strains ranged from
      66 to 74 and from 65 to 75, respectively. Two encapsulated and two non
      encapsulated strains were opsonized with homologous and heterologous pre-immune
      and immune bovine sera. Phagocytosis and intracellular killing of encapsulated
      strains increased significantly when opsonized with serum of cows vaccinated with
      a homologous and heterologous encapsulated strain. By contrast, no significant
      differences were observed when serum from cows vaccinated with a non-encapsulated
      strain was used. These results suggest that resistance to phagocytosis is a
      common feature among encapsulated strains of S. uberis, and that cross-reactivity
      exists between encapsulated strains.

PMID- 8578913
TI  - First report of paratuberculosis (Johne's disease) in sheep in Morocco.
AB  - Paratuberculosis (Johne's disease) was suspected in a flock of approximately 1000
      sheep after weight losses and scouring had increased in adult animals despite
      repeated anthelmintic treatment. A total of 10 ewes showing clinical symptoms
      were submitted to laboratory examination. Gross pathological and histological
      examination of tissue samples rendered results compatible with Johne's disease in
      all 10 ewes. The diagnosis could only be confirmed by cultural isolation and
      identification of Mycobacterium paratuberculosis in the faeces of two ewes. This
      is considered the first documented isolation of Mycobacterium paratuberculosis in
      sheep in Morocco.

PMID- 8578914
TI  - [Evaluation of the meat quality of game].
AB  - The carcasses of 140 roe deer, 129 wild boars, 81 red deer and 55 fallow deer
      were examined to determine meat quality with respect to the influence of typical
      hunting situations. After hunting, many carcasses had not been cooled, which
      significantly influenced meat-quality parameters. The pH-value, detected
      electrochemically, gave the most reliable results out of all the meat-quality
      parameters investigated. Determination of the pH-value with regard to the pH
      indexes ascertained for different points of measurement and types of game is
      helpful in properly judging the substantial quality of venison. Determination of
      electrical conductivity and water-holding capacity (Q) can be helpful in judging
      meat quality. The value of residual-blood content in judging substantial venison
      quality is, however, doubtful. The measurement of rapid glycolysis and the
      evaluation of rigor mortis are not appropriate for determining the substantial
      quality of venison.

PMID- 8578915
TI  - The effect of salinomycin on the control of Clostridium perfringens type-A
      infection in growing pigs.
AB  - Salinomycin (SAL), an ionophorous polyether antibiotic with growth promoter
      properties in pigs, has proved to be effective in controlling swine dysentery,
      porcine intestinal adenomatosis, and porcine haemorrhagic enteropathy. This study
      examines the ability of SAL to control C. perfringens type-A infection in growing
      pigs under field conditions. For 2 months, two groups of weaned pigs were offered
      feed either free of antibiotics, or medicated with 60 ppm and 30 ppm SAL for the
      first and second month respectively, and were compared with regard to their
      performance. The results showed that, whilst treatment did not have an effect on
      the mortality of pigs, the duration of pig diarrhoea during the trial period has
      been markedly reduced in the SAL group. Laboratory examinations have additionally
      shown that the number of carrier piglets has been reduced by SAL medication.
      Finally, treated pigs gained more weight and had a better feed-conversion ratio
      than untreated pigs during the 2-month trial period. It was concluded that SAL at
      the registered dose range, used as performance enhancer, can be helpful in
      controlling C. perfringens type-A infection in growing pigs.

PMID- 8578916
TI  - Rapid bioassay for detection of Bacillus anthracis in mice.
AB  - A rapid-bioassay method (RBA) of diagnosing anthrax was developed in mice. A
      standard RBA consisted of intraperitoneal inoculation of a suspected culture or
      of a suspension of raw infected animal tissues in four pairs of mice. At 60, 120
      and 180 min after inoculation, two mice were killed and smears and impression
      smears were made from the peritoneal fluid, heart blood, spleen, liver, and
      kidneys, and then fixed, stained and microscopically examined. Encapsulated rods
      seen in microscopy confirmed the diagnosis. The remaining pair of mice was kept
      for a 10-day observation period and served as a control. In the experiments
      described in this study, RBA showed a high efficiency. A vegetative culture of 18
      20 h of Bacillus anthracis growth demonstrated encapsulation in mice as early as
      120 min after inoculation; a culture of 3-5 or 6-12 h of growth showed
      encapsulation at 60 min. Old spores gave encapsulation at 180 min, but, if
      previously plated for 6 h, encapsulation was observed as early as 60 min after
      inoculation. Inoculation of raw infected tissues gave positive results at 120
      min. As compared with the challenged controls, no deviations between the results
      of RBA and the final diagnosis of anthrax were observed, but RBA appears to be 7
      17 times more rapid. Some variations of the standard RBA are also suggested.

PMID- 8578917
TI  - Vaccination of grasscutters with a multicomponent clostridial vaccine.
AB  - Grasscutter serum antibodies against Clostridium perfringens beta-toxin were
      titrated in an enzyme immunoassay. The procedure that is currently used for
      vaccinating domesticated grasscutters is discussed.

PMID- 8578918
TI  - In vitro efficacy of cefquinome (INN) and other anti-infective drugs against
      bovine bacterial isolates from Belgium, France, Germany, The Netherlands, and the
      United Kingdom.
AB  - The in vitro antibacterial activity of cefquinome (INN), an aminothiazolyl
      cephalosporin of the fourth generation of cephalosporins, was investigated by
      determining the minimal inhibitory concentration (MIC, microgram/ml) for 714
      bacterial isolates of bovine origin and comparing it with those of amoxicillin,
      amoxicillin and clavulanic acid, ceftiofur, cephapirin, enrofloxacin, gentamicin,
      kanamycin and oxytetracycline. Drug resistance was determined by using break
      points, which consider the dosage regimen and pharmacokinetics of the veterinary
      antimicrobials investigated. Cefquinome demonstrated a very high in vitro
      activity against bacterial isolates of Pasteurella spp., Escherichia coli and
      Salmonella spp. Overall, the level of resistance against the different anti
      infectives tested was lowest for cefquinome. For the remaining substances
      examined, in vitro activity and the level of resistance showed considerable
      differences. The chemical and pharmaceutical features of cefquinome are
      discussed.

PMID- 8578919
TI  - Changes in bovine mammary-secretion composition during early involution following
      intramammary infusion of recombinant bovine cytokines.
AB  - This study was designed to determine whether intramammary infusion of recombinant
      bovine interleukin-1 beta or interleukin-2 had any adverse influence on bovine
      mammary function during the early non-lactating period. Mammary glands of eight
      Jersey cows were infused with either 10 micrograms of interleukin-1 beta or 1.0
      mg of interleukin-2 following abrupt cessation of milking. Mammary secretions
      from each gland were collected from cows frequently during early involution and
      evaluated for changes in secretion composition. Percentage of milk fat and solids
      not-fat during the experimental period was variable for all treatments.
      Percentage of protein increased throughout the study for all treatments, but
      mammary glands treated with interleukin-1 beta had higher protein percentages.
      All interleukin-treated mammary glands had lower concentrations of lactose than
      controls. Mammary secretions from interleukin-1 beta treated glands had higher
      concentrations of lactoferrin at 7 and 14 days of involution. Similarly, mammary
      secretions from interleukin-2 treated glands had higher concentrations of serum
      albumin on day 3 of involution and throughout the remainder of the study.
      Concentration of citrate and the citrate: lactoferrin molar ratio generally
      decreased throughout the study for all treatment groups. Concentration of alpha
      lactalbumin in mammary secretions decreased throughout the study and was not
      different between treatment groups. Though significant changes in mammary
      secretion composition due to the presence of cytokines were observed in this
      study, resulting in an apparent acceleration of involution, there was no
      indication that these changes adversely affected normal bovine mammary function
      during the early non-lactating period.

PMID- 8578920
TI  - Experimental oral infection of specific pathogen-free laying hens and cocks with
      Salmonella enteritidis strains.
AB  - A total of 105 specific pathogen-free (SPF) laying hens and eight cocks were
      orally infected with strains of Salmonella enteritidis. The organs of these
      animals were examined bacteriologically for up to 6 weeks post infectionem
      (p.i.). One-half of the eggs laid on a single day were examined 1 day after
      laying, and the other half 28 days after laying. The siderophore, ferrioxamine E,
      was added to the pre-enrichment medium. A high correlation was found to exist
      between colonization of the caecum by salmonellas and the level of contamination
      of the egg shell. No correlation was found between the contamination of the egg
      shell and that of the egg content. The strains used for infection were not
      recovered from any yolk out of a total of 938 eggs. S. enteritidis was isolated
      from the albumen in four cases (0.4%). Storage of the eggs for 28 days after
      laying resulted in a decrease in the frequency of salmonella detection on the egg
      shell and in the egg content. The strains used for infection could be isolated
      from various sections of the sexual organs for up to 2 weeks p.i. S. enteritidis
      was most frequently found in the ovary and rarely in the oviduct, but never in
      the pre-ovulatory mature follicles. In the groups that included salmonella
      infected cocks, the salmonella detection frequency did not increase either for
      the egg content or for the organs of the laying hens. It seems that primary
      vertical transmission of salmonellas occurs, in rare cases, as a result of an
      infection of the albumen but not of the yolk.

PMID- 8578921
TI  - Infection model for hatching chicks infected with Salmonella enteritidis.
AB  - A total of six different strains of Salmonella enteritidis (phage type 4) were
      used for the artificial infection of the egg yolk and albumen of SPF hatching
      eggs. An artificial yolk infection with low infection doses of S. enteritidis
      resulted in a considerable multiplication of salmonellas in the egg after a short
      time and a rapid embryonic death. After inoculation of 10(3) cfu of different S.
      enteritidis strains into the albumen, living day-old chicks infected with
      salmonellas were hatched. This model corresponds to a primary vertical
      transmission of salmonellas and permits the investigation of problems concerning
      the pathogen/host relationship.

PMID- 8578922
TI  - A sensitive double-antibody enzyme-linked immunosorbant assay for bovine
      myeloperoxidase and its application to serum and neutrophil extracts.
AB  - The heme enzyme myeloperoxidase (MPO), with a spectral A430/A280 ratio > 0.78,
      was purified from isolated bovine neutrophils. Using highly specific anti-MPO
      monoclonal and anti-MPO polyclonal antibodies raised against MPO, a specific and
      sensitive double-antibody enzyme-linked immunosorbant assay (ELISA) was developed
      to measure bovine MPO in serum and neutrophil extracts. The ELISA shows good
      precision and accuracy, with intra- and interassay coefficients of variation of <
      10% for MPO concentrations ranging from 0.5 to 50 ng/ml. The accuracy of the
      ELISA for measuring MPO in bovine serum was further confirmed by the similarity
      between the standard curve and curves obtained with successive dilutions of MPO
      rich serum samples. The mean analytical recovery of MPO from serum was
      approximately 90%. Long delays between blood sampling and serum preparation were
      found to affect the level of MPO in the serum. Mean MPO values in the serum of
      healthy adult cows were 6.5 ng/ml, with a range of 3.5-15.3 ng/ml. In dairy cows
      with acute mastitis, mean serum MPO values were approximately 30 ng/ml, with a
      range of 6.0-59.6 ng/ml, and the elevation was markedly higher than the normal
      values (P = 0.0001). In isolated neutrophils from healthy cattle, MPO
      concentrations were found to be 7 x 10(-4) ng, with a range of 6.5-8.3 x 10(-4)
      ng/neutrophil. The ELISA was used to study the distribution of MPO in the bovine
      neutrophil granules; it was found to be localized to one distinct compartment.

PMID- 8578923
TI  - Copro-antibody in calves from dams vaccinated against Salmonella typhimurium.
AB  - Calves received colostrum either with (positive colostrum) or without (negative
      colostrum) anti-Salmonella typhimurium antibodies. Regarding the detectability of
      copro-antibodies, the following observations have been made. In calves that had
      been given positive colostrum on day 4 post natum (p.n.), copro-antibodies were
      detectable over 7 days, while in those that had received positive colostrum on
      day 1 p.n. copro-antibodies were detectable over 45 days. After supplying highly
      positive colostrum, copro-antibodies were found over a period of 8 weeks, and
      after supplying weakly positive colostrum, they were found over a period of 5
      weeks. It is concluded that serum antibodies are transferred to the intestine for
      maximum local protection, and that there exists a preference for the intestinal
      system regarding the distribution of salmonella antibodies. Challenge infection
      on day 5 p.n. of calves that had received highly positive colostrum resulted in a
      copro-antibody gap that reached the limit of detectability in two calves that
      were excreting salmonellas. Challenge infection of calves that had received
      negative colostrum provoked a local IgM and IgA antibody response.

PMID- 8578924
TI  - Borrelia in pigeons: no serological evidence of Borrelia burgdorferi infection.
AB  - In order to clarify the supposed involvement of urban pigeons (Columba livia
      livia) in the epidemiology of Lyme disease, the presence of antibodies against
      Borrelia burgdorferi and Borrelia anserina in pigeons' sera, collected in 12
      areas of northern and central Italy, was evaluated. This evaluation was carried
      out using a classic immunofluorescence assay (IFA), a surface immunofluorescence
      assay (SIFA) and a standard Western Blot (WB) assay. A total of 104 out of 3,186
      (3.26%) serum samples were positive for both spirochetes when tested by IFA, with
      titres ranging from 1/40 to 1/1280. All positive specimens showed the same or a
      higher reactivity against B. anserina than against B. burgdorferi. Of the IFA
      positive samples, 30 were tested by WB and SIFA to evaluate further the
      specificity of the antibody response, i.e. to try to clarify against which
      spirochete the antibodies were raised. The presence of antibodies against the 23
      kDa protein exclusive to B. anserina, and against epitopes which are not surface
      exposed and which are common to B. anserina and B. burgdorferi, was assessed by
      WB and SIFA. No serological evidence that B. burgdorferi can infect pigeons was
      found.

PMID- 8578925
TI  - Possible naturally occurring zeranol in bovine bile in Northern Ireland.
AB  - Zeranol and two Fusarium toxins, alpha-zearalenol and beta-zearalenol, were
      confirmed by gaschromatography/mass spectrometry (GC/MS) in bovine bile samples
      referred to this laboratory for analysis. No evidence of zeranol abuse was found
      on-farm. Given the recent suggestion that zeranol might arise from the metabolism
      of these Fusarium toxins, and the finding of zeranol in bovine and ovine urine
      across the EU, it was concluded that the residues had arisen as a result of
      natural metabolism.

PMID- 8578926
TI  - Microdialysis as a tool to assess interstitial norepinephrine levels in adipose
      tissue of spontaneously hypertensive rats.
AB  - The microdialysis technique was applied to the study of norepinephrine (NE)
      metabolism in white adipose tissue of spontaneously hypertensive (SHR, n = 6) and
      normotensive Wistar-Kyoto (WKY, n = 6) rats. Mean concentrations of interstitial
      NE were much higher in SHR as compared to WKY (mean +/- SEM: 980.9 +/- 125.6
      pg/ml vs 520.7 +/- 96.1 pg/ml; p = 0.01) over the 180 min experimental period.
      These results are consistent with the hypothesis that sustained outflow from
      nerve endings of the peripheral sympathetic system may play a role in the
      maintenance of arterial hypertension. Owing to its low invasiveness, the
      microdialysis technique allows to continuously monitor NE extracellular levels in
      conscious and freely-moving animals.

PMID- 8578928
TI  - The vascular complications of diabetes mellitus.

PMID- 8578927
TI  - Association of relative nocturnal hypertension and autonomic neuropathy in
      insulin-dependent diabetic children.
AB  - Twenty-four hour BP and heart rate measurements were carried out in fourteen
      newly diagnosed-, and in twenty-eight diabetics with 5-13 years of duration; and
      in eight healthy control children. Mean arterial BP rose at night in five-, fell
      slightly (less than 10%) in five- and fall markedly (more than 10%) in eighteen
      diabetics with longer duration of the disease. The diurnal-nocturnal difference
      of mean arterial pressure was significantly lower in the groups with nocturnal BP
      rise and slight nocturnal BP fall, compared to the control group (< 0.001; p <
      0.01, respectively). The diurnal-nocturnal differences of heart rates were
      significantly lower in diabetics with relative "nocturnal hypertension" compared
      to the control group (p < 0.05). The presence of subclinical signs of diabetic
      autonomic neuropathy was significantly higher in patients with nocturnal BP rise
      and slight nocturnal BP fall compared to patients with marked nocturnal BP fall
      and newly diagnosed diabetics (chi squared p = 0.02 and p = 0.01, respectively).
      In conclusion, the prevalence of autonomic symptoms in diabetic children could be
      related to change in diurnal/nocturnal arterial BP, however longitudinal studies
      of ABPM are needed to define, whether patients with abnormal BP profiles are
      candidates for the development of diabetic vascular disease.

PMID- 8578929
TI  - Interleukin-6: a pathogenetic role in the postmenopausal osteoporosis?

PMID- 8578930
TI  - Dehydroepiandrosterone sulphate in the diagnosis of osteoporosis.
AB  - Several data suggest that adrenal androgens have an important role in the
      pathogenesis of postmenopausal osteoporosis. To study the possible relationship
      between bone density and serum levels of dehydroepiandrosterone sulphate (DHEAS)
      we investigated 105 women (45-69 years). Serum DHEAS level was significantly
      lower in the osteoporotic group than in the normal one. The serum level of DHEAS
      decreased significantly with age in both groups. We established a significant
      positive correlation between DHEAS and bone mineral density of the lumbar spine
      and femoral neck, and bone mineral content of radius midshaft as well. Since
      there was no significant difference between the two groups regarding oestrogens,
      we suggest that DHEAS may have a non-oestrogenic effect on bone. We conclude that
      serum DHEAS may have a useful indicator of low bone mineral density in peri-and
      postmenopausal women.

PMID- 8578931
TI  - Guide-lines to the treatment of patients with X-linked hypophosphatemic rickets.
AB  - The causes of the development of nephrocalcinosis in familial hypophosphatemic
      rickets (FHR) are reviewed. The treatment combines vitamin D or 1,25
      dihydroxyvitamin D and oral phosphate supplementation. Hypercalcaemia and
      hypercalciuria were thought to cause the renal calcification. On the basis of the
      data of eighteen patients with familiar hypophosphatemic rickets we have found
      that the main difference between the treatment of patients having
      nephrocalcinosis and those with normal renal morphology consisted in the dose of
      oral phosphate intake. Patients with nephrocalcinosis received significantly
      higher doses of oral phosphate (130 mg/kg/day versus 70 mg/kg/day, p < 0.01).
      Correspondingly, their urinary phosphate excretion was also significantly higher
      (p < 0.01). There was no difference between the two groups with respect of the
      doses of vitamin D and urinary calcium excretion. It can be concluded, that high
      concentrations of urinary phosphate can lead to nephrocalcinosis even if urinary
      calcium concentration is normal. In order to prevent nephrocalcinosis in patients
      with X-linked hypophosphatemia, the following guide-lines could be recommended:
      1) urinary calcium excretion should be kept lower, than the usually allowed < 4
      mg/kg/day; 2) oral phosphate supplementation should not exceed 100 mg/kg/day, 3)
      patients should be encouraged to drink large amounts of water, 4) regular
      ultrasound controls should be part of the routine follow-up.

PMID- 8578933
TI  - Lipoprotein (a): effect of detraining.
AB  - Plasma levels of lipoprotein (a), total cholesterol, triglycerides, HDL
      cholesterol, LDL-cholesterol, apo-protein Al and apoprotein B were evaluated for
      8 long-distance runners during the XXIII New York Marathon, with blood samples
      being taken before and after the race, and after one month of detraining. After
      detraining lipoprotein (a) increased significantly both with respect to basal
      values and especially with respect to immediately post-race values. Negligible
      and predictable modifications of the other metabolic parameters evaluated, were
      observed. No correlation was found between lipoprotein (a) and the
      anthropometrical data and metabolic parameters considered.

PMID- 8578932
TI  - Triacylglycerol composition of human endogenous lipoproteins.
AB  - The intact triacylglycerol profiles for VLDL and LDL of healthy and primary
      hypertriglyceridemic patients were obtained by high temperature capillary gas
      chromatography. The data were treated by the methods of computerized analysis.
      Marked individual heterogeneity was found. This can be explained by either
      genetic polymorphism or multiple lipoprotein triacylglycerol pools within one
      density class. Suspecting genetic polymorphism and determination type IV
      (familial hypertriglyceridemia) seems to be a pure overproduction of endogenous
      VLDL, while in type II B (familial combined hyperlipidemia) an altered mechanism
      of triacyglycerol synthesis can be supposed.

PMID- 8578934
TI  - Apolipoprotein polymorphism in Hungary.
AB  - The disorders of plasma apolipoprotein metabolism caused by a number of genetic
      and environmental factors are associated with atherosclerosis. Because of the
      distinct structural, epidemiological and genetic properties of apolipoproteins we
      have analyzed some potentially important phenotypical markers of
      apolipoproteins(a)/Lp(a)/,E (apo E) and A-IV (apo-A-IV). In our Hungarian study
      population (n = 202) the frequency of Lp(a) concentrations (mean 10.5 +/- 13.5
      mg/dl) and phenotypes (the dominance of high molecular weight isoforms) show
      similar distribution that of other Caucasian populations. We have also found an
      inverse relationship between the concentrations and phenotypes of Lp(a). In
      accordance with earlier observation apo E polymorphism exerts a definitive effect
      on determinating variation of plasma cholesterol in our population. The average
      excesses of apo E alleles on serum cholesterol concentration were: E2 -0.34, E3 
      0.01 and E4 +0.26 mmol/l. The apo E3 (0.807) allele was the most frequent
      followed by E4 (0.129) and E2 (0.064). In contrast, the apolipoprotein A-IV
      frequency distribution is significantly different from other Caucasian
      populations (p < 0.05). The frequency of apo A-IV alleles are f(A-IV1) = 0.95,
      f(A-IV2) = 0.039 and f(A-IV3) = 0.002. The association of apo A-IV phenotypes
      with HDL-cholesterol concentrations, which was previously described for two other
      European populations was only of borderline significance (p < 0.08). In
      conclusion, the results show the impact of phenotypic variation of
      apolipoproteins on the normal variation in the plasma lipid profile in Hungarian
      blood donors.

PMID- 8578935
TI  - Lipoprotein Lp(a) and cerebrovascular disease in the elderly: correlations with
      the severity of extracranial carotid atherosclerosis assessed by ultrasonography.
AB  - High levels of lipoprotein Lp(a) are related to cerebrovascular disease clinical
      manifestations, as well as to the severity of extracranial carotid
      atherosclerosis assessed by ultrasonography. In order to investigate the
      relationship of Lp(a) to the severity of carotid atherosclerosis in the elderly,
      100 subjects, aged 78.5 +/- 0.6 yrs underwent an echo-color-doppler scanning of
      carotids; atherosclerosis severity, assessed as maximum percentage stenosis,
      presence of complicated plaque and Intima-Media Thickness (IMT), was related to
      Lp(a) levels, assayed by an immunoenzymatic procedure. A slight association
      between Lp(a) and CVD clinical manifestations was apparent only in subjects under
      78 yrs and for Lp(a) values above 25 mg/dL. Lp(a) levels were not related either
      to the degree of stenosis, the presence of complicated plaque, or IMT. As for
      other selected risk factors, while no relationship was found for clinical CVD and
      IMT, the maximum percentage of stenosis and the presence of complicated plaques
      were positively related to LDL-cholesterol in subjects under 78 yrs. We can
      conclude that Lp(a), albeit unrelated to the severity of extracranial vessel
      atherosclerosis, maintains a role as cerebrovascular risk factor in the elderly,
      being slightly related to clinical manifestations; however its discriminant power
      is lower than in middle-aged people and further decreases throughout ageing.

PMID- 8578936
TI  - Microangiopathy in primary hyperlipoproteinemia.
AB  - The microvascular basement membrane thickness were investigated by electron
      microscope within skeletal muscle of 17 untreated patients with primary
      hyperlipoproteinemia. The average of minimal basement membrane thickness of
      hyperlipidemic patients were significantly different (p < 0.001) from that of the
      controls (127 +/- 44.6 nm vs 39.9 +/- 12.4 nm). In conclusion,
      hyperlipoproteinemia without diabetes mellitus might contribute to the damage of
      the capillary vessel wall.

PMID- 8578937
TI  - Joint scientific meeting of disorders of metabolism: experimental and clinical
      studies. Sote--Budapest and medical faculty of the University. Parma, 3-4 June
      1994. Proceedings.

PMID- 8578938
TI  - Determination of cerebral oxygen consumption and blood flow by magnetic resonance
      imaging.
AB  - Simultaneous 17O and 19F magnetic resonance imaging were used to determine the
      concentrations of H2(17)O and CHF3 in 0.8 cc voxels in the cat brain during in-
      and exhalation of a gas mixture containing both 17O2 and CHF3. The arterial time
      course of H2(17)O was determined by 17O MR analysis of arterial samples withdrawn
      during the inhalation period and the arterial time concentration of CHF3. The
      brain data and the arterial data for the two tracers were used to calculate the
      cerebral oxygen consumption (CMRO2) and the cerebral blood flow (CBF). The
      average values of CMRO2 and CBF for a 0.8 cc voxel in the parietal cortex were
      1.5 +/- 0.5 mmol/kg/min and 38 +/- 15 ml/100g/min, respectively. 17O/19F MR
      imaging approach has the potential to image CMRO2 and CBF simultaneously in
      humans and might become a strong diagnostic tool.

PMID- 8578939
TI  - Ion and metabolic disturbances after global and focal cerebral ischemia.
AB  - We focus our attention in this presentation to the extracellular ionic changes
      during and after local ischemia and in repetitive versus single global ischemia.
      In the cat stroke model of MCA occlusion a considerable variability in the
      severity of ischemia was observed. This was demonstrated in electrical activity
      (ECoG), NAD/NADH fluoro-reflectometry and extracellular ionic changes. A striking
      experience was, that the K+ recovery is rather fast even after two hours of
      ischemia, and this is partly due to maintained activity of the sodium-potassium
      pump. After the MCA release a secondary acidosis occurs, which is the result of
      excess lactic acid production. This lactacidosis is certainly contributes to the
      late morphological damage. The repeated acidotic insult (in gerbil model of
      global cerebral ischemia) could be the cause of the more severe morphological and
      blood-brain-barrier damage in the repetitive ischemia too. The acidosis in many
      cases is even more pronounced after relieving the carotid arteries. This
      secondary acidosis causes endothelial damage and vasogenic oedema.

PMID- 8578940
TI  - Convergence of pallidal and cerebellar outputs on the frontal motor areas.
AB  - The general pattern of the organization of the thalamo-cortical projections to
      the agranular frontal cortex of the monkey is still matter of debate. An
      important issue is whether each motor area is the target of a single thalamic
      nucleus or it receives afferences from multiple thalamic sources. In this light
      it is of interest to determine whether the basal ganglia and cerebellar outputs,
      which are segregated in the thalamus, remain segregated also at the cortical
      level or, on the contrary, both converge on the same cortical areas. In the
      present article we present data concerning the thalamic input to mesial area 6
      obtained with cortical injections of retrograde neural tracers. This cortical
      sector, classically considered as coextensive with the so called supplementary
      motor area (SMA), was recently found to be formed by two independent anatomo
      functional areas: F3 (SMA-proper) and F6 (pre-SMA). On the basis of the
      neurophysiological properties of the two areas we have proposed that F6 plays a
      hierarchically higher role in motor control than F3. The present results allow us
      the following main conclusions: a) Each motor area is the target of a distinct
      set of thalamic nuclei. b) Each area is the target of both basal ganglia and
      cerebellar outflows. c) As far as the basal ganglia input is concerned, F3 is a
      part of the so called "basal ganglia motor loop", whereas, F6 belongs to the
      "basal ganglia complex loop". This differential basal ganglia input provides
      further evidence in favor of a higher hierarchical role of F6 in comparison to
      F3.

PMID- 8578941
TI  - Failure of dopamine metabolism: borderlines of parkinsonism and dementia.
AB  - Dementia in parkinsonian patients is estimated to 10-40%. Several factors may
      take part in the development of cognitive impairment: i/ defective function of
      subcortico-cortical pathways including the mesocorticolimbic dopamine deficiency
      with cell loss in medial substantia nigra, the degeneration of noradrenergic,
      serotonergic and cholinergic systems ii/ cortical and limbic Alzheimer pathology
      iii/ cortical Lewy bodies iv/ vascular alterations. Using HMPAO SPECT we
      distinguished three main types of hypoperfusion in Parkinson patients with
      dementia: i/ predominantly frontal lobe type ii/ posterior ("Alzheimer-like")
      type iii/ multiple small vascular defects. Neuropsychological investigation was
      based on the use of MMSE, word pair, digit span, verbal fluency, Lurija's tapping
      tests. In addition CURS and Hachinski's score were also applied. Selegiline
      (JumexR) therapy was introduced and the patients were followed for at least 60
      days. Selegiline improved significantly the MMSE values and verbal fluency in the
      "frontal lobe" type further the memory functions in "Alzheimer-like" patients.
      The mechanism is still not clarified, the increased dopaminergic tone should be
      taken into account.

PMID- 8578942
TI  - Identification of enzyme deficiencies resulting in congenital adrenal
      hyperplasia.
AB  - Selective screening for congenital adrenal hyperplasia (CAH) by blood spot 17
      hydroxyprogesterone measurements is a practical option than can yield valuable
      clinical information and more accurate estimate of incidence. Simultaneous
      investigation of serum and urinary steroids allows detection of late-onset types
      of CAH.

PMID- 8578943
TI  - Three-dimensional architecture of human cutaneous vascular lesions: a scanning
      electron microscopic study of corrosion casts.
AB  - Corrosion casts were made from angiosarcoma of the scalp of an elderly person,
      Klippel-Trenaunay syndrome, pseudo-Kaposi's sarcoma, diffuse neonatal
      hemangiomatosis, cavernous hemangioma and arteriovenous malformation and were
      examined by scanning electron microscopy (SEM). The normal scalp from a cadaver
      was studied as a control for the angiosarcoma of the scalp. the SEM of the
      vascular corrosion casts clearly demonstrated the fine three-dimensional (3-D)
      architectures of malignant and benign cutaneous vascular lesions; the superficial
      fine and medium-sized vascular networks of the skin were replaced by abnormal
      balloon-like dilatations, extravasated fringes, glomerular structures, sinusoidal
      vessels or localized bulla-like structures of the capillary loops, depending on
      the nature of the cutaneous vascular lesions. The corrosion cast technique is
      helpful for understanding the 3-D patterns of various vascular lesions.

PMID- 8578944
TI  - Electronic infrared thermography as a method of assessing herpes labialis
      infection.
AB  - The purpose of this study was to ascertain the applicability of infrared
      thermography to study the natural history of herpes labialis lesions. Since
      thermography is capable of detecting changes not visible to the naked eye, then
      it may be of value in complementing clinical examination of the various stages of
      herpes labialis. In addition, thermographic imaging is quantitative and therefore
      allows for an accurate assessment of temperature changes accompanying the disease
      process, both within patients and between patients. Ten female patients suffering
      from herpes labialis were studies (mean age 25 +/- 5 years). In all cases herpes
      simplex virus Type 1 was isolated by the HEP-2 technique. No treatment was
      instituted and patients were clinically assessed and thermographically imaged
      daily from the prodromal phase through to resolution. A marked temperature
      increase (1 degree C minimum) was observed within hours of the prodromal phase
      and maintained until day 4. As the lesions progressed to vesicle formation, the
      central area of the vesicle was noted to be cooler due to the insulating effect
      of the fluid. Even by day 6 a significant 0.5 degree C temperature increase over
      background was present at the involved site and this returned to normal within 8
      to 10 days. The area of thermographic involvement was three to four times larger
      than the clinical area of involvement (60-100 mm2 versus 20-25 mm2). To assess
      reproducibility, we also studied patients through two additional untreated herpes
      labialis episodes. The prodromal phase was reproducible thermographically and
      characterized by a temperature increase of 1.42 degrees C +/- 0.2 degrees C.
      Thermographic imaging may represent a new approach to quantifying disease
      activity in herpes labialis, particularly in the subclinical prodromal stage.

PMID- 8578945
TI  - Comparison of the effect of hydrocortisone, hydrocortisone-17-butyrate and
      betamethasone on collagen synthesis in human skin in vivo.
AB  - It has been shown previously that topical corticosteroid treatment decreases
      collagen synthesis in human skin in vivo and that the adverse effects are due to
      reduced collagen synthesis. The aim of the present study was to evaluate the
      effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on
      collagen synthesis in human skin in vivo. Fourteen healthy male volunteers
      applied hydrocortisone, hydrocortisone-17-butyrate, betamethasone and vehicle
      twice a day for one week to four separate areas marked on their abdominal skin.
      The collagen synthesis rate in the skin was measured by assaying collagen
      propeptides from the suction blisters induced on the treated areas. Aminoterminal
      propeptide of type I procollagen (PINP) and aminoterminal propeptide of type III
      procollagen (PIIINP) were measured from skin blister fluid using
      radioimmunoassays. Skin thickness was measured with ultrasound. Hydrocortisone
      decreased the two propeptides studied in the suction blister fluids less than did
      hydrocortisone-17-butyrate and betamethasone, but the interindividual variation
      was great. Hydrocortisone-17-butyrate and betamethasone had almost similar
      decreasing effects on the propeptides in the suction blister fluid.
      Hydrocortisone decreased the concentrations of PINP and PIIINP by about 35%. In
      some subjects (4/14) the decline of the collagen propeptide levels was over 50%.
      The decline in the concentration of PINP was 63% by hydrocortisone-17-butyrate
      and 69% by betamethasone, while the decrease in PIIINP was 55% by hydrocortisone
      17-butyrate and 62% by betamethasone. None of the treatments had any effect on
      skin thickness within one week. In conclusion, it seems that hydrocortisone is
      less atrophogenic than hydrocortisone-17-butyrate and betamethasone, as shown by
      radioimmunoassays for collagen propeptides. The order of inhibitory potency of
      the three glucocorticoids on collagen synthesis was hydrocortisone <
      hydrocortisone-17-butyrate < betamethasone. Thus, assay of collagen propeptides
      from suction blisters can be used to screen various steroids with respect to
      their action on collagen synthesis.

PMID- 8578946
TI  - Topical cis-urocanic acid suppresses both induction and elicitation of contact
      hypersensitivity in BALB/C mice.
AB  - Cis-urocanic acid, converted from trans-urocanic acid in stratum corneum by
      ultraviolet B irradiation, has been shown to impair contact hypersensitivity
      induction. To study whether topical cis-urocanic acid also alters contact
      hypersensitivity elicitation, as well as immediate hypersensitivity and acute
      irritation, we treated mice with 1% topical cis-urocanic acid or vehicle prior to
      induction or elicitation of hypersensitivity to contact allergen oxazolone or
      respiratory allergen trimellitic anhydride or prior to acute irritation from
      croton oil. Topical cis-urocanic acid suppressed both induction and elicitation
      of contact hypersensitivity to oxazolone. However, no effect by cis-urocanic acid
      on induction or elicitation of trimellitic anhydride allergy or croton oil
      irritation was seen. The possible efficacy of topical cis-urocanic acid as a
      treatment of inflammatory skin diseases responsive to ultraviolet B irradiation
      may be worthwhile to investigate.

PMID- 8578947
TI  - Influence of activation and differentiation of cells on the effectiveness of
      photodynamic therapy.
AB  - Photodynamic therapy combines photosensitizers absorbing light in the red
      spectral region and irradiation with light of the corresponding wavelength. To
      analyse the influence of cell differentiation on susceptibility to photodynamic
      therapy, we compared the proliferation inhibition induced by photodynamic therapy
      on normal human keratinocytes, spontaneously transformed human keratinocyte cell
      line HaCat and on squamous cell carcinoma lines. Cells were irradiated with
      polychromatic methylene blue as well as the precursor of protoporphyrin, 5
      aminolevulinic acid. When incubated with Photosan-3, normal human keratinocytes
      exhibited and ED50 about 10-fold lower than the other cell lines studied. When
      methylene blue and 5-aminolevulinic acid were used, photodynamic therapy had
      comparable effects on all cell types. Stimulation of normal human keratinocytes
      with either EGF-alpha or IFN-gamma resulted in an increase susceptibility to
      photodynamic therapy when 5-aminolevulinic acid was used. This effect was more
      pronounced in the case of EGF-alpha. Our experiments suggest that activation and
      differentiation are two important parameters determining susceptibility to
      photodynamic therapy.

PMID- 8578948
TI  - The influence of the pH-value on the growth of Brevibacterium epidermidis in
      continuous culture.
AB  - Brevibacterium epidermidis is a major component of the bacterial flora of certain
      skin surface biotopes, characterized by a comparatively high pH-value. The
      presence of Brevibacterium epidermidis seems to be linked to the production of
      malodour. Skin surface pH has been found to be a major factor of bacterial growth
      on the skin. In order to find out if this might also apply to Brevibacterium
      epidermidis, this microorganism was grown in vitro in continuous culture using a
      chemostat. Specific growth rate and density of colony forming units were well
      correlated. While the organism grew readily from pH 5.5 to 8.5, this was not the
      case with a pH of 5.0. Thus pH-shifts induced by cosmetic procedures can only
      prevent unpleasant body odour due to abundant growth of bacteria if the pH-value
      is decreased to 5.0 or less.

PMID- 8578949
TI  - Seasonal variation of tyrosinase activity in serum.
AB  - Serum samples for the analysis of tyrosinase activity were obtained from 10
      healthy subjects in autumn, winter and summer. Tyrosinase was purified from 100
      microl serum by adsorption to concanavalin A sepharose, the tyrosinase adsorbed
      to the gel being separated from other components by centrifugation. The gel was
      suspended in a buffer containing 5-hydroxy-indole-3-acetic acid as an antioxidant
      and incubated for 2 min with L-cysteine and D-L-dopa at 37 degrees C. The 5-S-L
      cysteinyl-L-dopa formed was measured by HPLC and electrochemical detection.
      Tyrosinase has high stereo-specificity for the L-enantiomer of dopa, and
      correction for non-specific oxidation was made by simultaneous measurement of 5-S
      L-cysteinyl-D-dopa formed from D-dopa. Whereas the oxidation of L-dopa catalysed
      by tyrosinase ws inhibited by L-tyrosine, the non-specific oxidation of D-dopa
      was not. Mean serum tyrosinase activity was 0.9 nkatal/l in summer, 0.8 nkatal/l
      in autumn and 0.4 nkatal/l in winter. The range of tyrosinase activity was much
      higher in summer and autumn than in winter.

PMID- 8578950
TI  - Urinary excretion of melanocyte metabolites during treatment with chloroquine
      phosphate.
AB  - The antimalarial drug chloroquine is also used in the prevention of
      photodermatoses and in patients with inflammatory connective diseases. The drug
      binds strongly to melanin. Melanocytic activity can be studied by analysis of the
      urinary markers of eumelanin (6-hydroxy-5-methoxyindole-2-carboxylic acid, 6H5MI
      2-C) and phaeomelanin (5-S-cysteinyl-dopa, 5-S-CD). To determine whether
      chloroquine interacts with this activity, we measured the urinary excretion of
      the two metabolites in 16 patients with either systemic or discoid lupus
      erythematosus, polymorphic light eruption or rheumatoid arthritis, during a
      period with and without treatment with chloroquine phosphate. Two control groups
      consisting of 7 untreated patients and 10 healthy subjects were also included in
      the study. During medication, there was a significant increase in 5-S-CD
      excretion, while the excretion of 6H5MI-2-C was not significantly affected. No
      significant changes in the excretion of any of the two urinary markers were found
      in the untreated patients, while a non-significant increase in 5-S-CD excretion
      was seen in the healthy controls at the follow-up.

PMID- 8578951
TI  - Retinoids and fibrinolysis.
AB  - Vitamin A and its analogues have been reported to increase the release of tissue
      plasminogen activator in vitro. The aim of the present study was to reevaluate
      these findings and to investigate whether retinoids in doses used in
      dermatological therapy could enhance the release of endothelial fibrinolytic
      factors. Our results showed that endothelial cells incubated in vitro with
      retinoic acid increased the release of tissue plasminogen activator to the
      supernatant without concomitant secretion of plasminogen activator inhibitor-1.
      In patients treated with isotretinoin or etretinate these findings were
      confirmed, showing enhanced baseline tissue plasminogen activator concentrations
      in plasma in association with unchanged levels of plasminogen activator inhibitor
      1 and von Willebrand factor. These findings are consistent with chronically
      augmented tissue plasminogen activator secretion without evidence of endothelial
      cell damage and may be of importance for the interpretation of the safety of lon
      term therapy with regard to retinoid-induced hyperlipemia and the development of
      cardiovascular disease.

PMID- 8578952
TI  - Raised serum androgens and increased responsiveness to luteinizing hormone in men
      with acne vulgaris.
AB  - We have investigated the hormone profiles and the relationship between serum
      testosterone and luteinizing hormone in men with long-standing acne vulgaris. In
      the controls, age correlated with the free androgen index and with serum
      dehydroepiandrosterone-sulphate, so for the purposes of comparison 33 men with
      acne vulgaris were age-matched against 33 controls. Compared with controls, the
      acne patients had higher medians of serum androstenedione, testosterone and free
      androgen index. In both groups there was a significant correlation between
      testosterone and luteinizing hormone levels. For a given level of luteinizing
      hormone the patients with acne tended to have higher levels of serum testosterone
      than normal controls. These results indicate that in this group of men with long
      standing acne there was either increased responsiveness of the target organ to
      luteinizing hormone or there was an increased amount of androgen-secreting
      tissue.

PMID- 8578953
TI  - Adenosine deaminase in progressive systemic sclerosis.
AB  - The aim of the present study was to confirm the increase of adenosine deaminase
      (ADA) activity in progressive systemic sclerosis (PSS), described by Sasaki &
      Nakajima, and to compare plasma ADA activity of patients in different stages of
      the disease. Enzyme activity was measured with a colorimetric assay. The 48
      patients were subdivided into 3 groups: subgroup 1 (n = 10), disease still
      limited to the skin; subgroup 2 (n = 21), involvement of the skin and oesophagus;
      and subgroup 3 (n= 17), involvement of the skin and multiple internal organs. ADA
      levels were highest in subgroup 3. However, the difference with respect to
      subgroup 2 did not reach statistical significance. Subgroup 1 was different from
      controls and subgroups 2 and 3 (p<0.001). Our results confirm that ADA activity
      is increased in PSS, and that this finding is observed even in the early stages
      of the disease process. We speculate that the increase in ADA, a well-known
      marker of T-cell activation, might be an indicator of disease activity in PSS, in
      the beginning as well as during phases of exacerbation in later stages of the
      disease.

PMID- 8578954
TI  - Occurrence and clinical features of sensitization to Pityrosporum orbiculare and
      other allergens in children with atopic dermatitis.
AB  - One hundred and nineteen consecutive cases of children with atopic dermatitis
      aged 4-16 years (73 girls) from a pediatric dermatology outpatient clinic were
      included in a study of atopic sensitization. Structured interviews and clinical
      investigations were performed. IgE antibodies to common inhalant allergens,
      Pityrosporum orbiculare, Candida albicans, Tricophyton rubrum and Staphylococcus
      aureus were detected. Specific IgE antibodies frequently occurred to pollens,
      animal epithelia, C. albicans, house dust mites and moulds, whereas specific IgE
      antibodies to potential skin allergens were less prevalent. Twenty-six children
      (21.8%) had IgE antibodies to P. orbiculare, 14 (11.8%) to T. rubrum and 3 (2.5%)
      to S. aureus. Atopic dermatitis in children with one or several RAST positivities
      was worse, with a more chronic course, higher total eczema score, more frequent
      distribution in the head-neck-face regions and more itch compared to the children
      without serum detectable IgE antibodies. Severe itch disturbing nightly sleep was
      the only clinical feature that characterised P. orbiculare-positive cases.
      Allergy to P. orbiculare appears to be of little importance in early childhood
      atopic dermatitis but is likely to carry a poor prognosis.

PMID- 8578955
TI  - An epidemic of tinea corporis caused by Trichophyton tonsurans among wrestlers in
      Sweden.
AB  - An epidemic of tinea corporis due to Trichophyton tonsurans among wrestlers in
      Sweden is described. Totally 19 patients, 14 patients from Malmo and 5 from
      Gothenburg, were found. The suspected source of this epidemic was from a
      wrestlers' team from the USA visiting Sweden in April, 1993. All patients were
      treated orally with either griseofulvin, fluconazole or terbinafine, and all were
      cured. To prevent spreading, epidemiological tracing of secondary cases is
      important.

PMID- 8578956
TI  - Hyperpigmentation due to calcipotriol (MC 903) plus heliotherapy in psoriatic
      patients. Three case reports.
AB  - Calcipotriol is a synthetic analogue of vitamin D, used in the treatment of
      psoriasis. Until now no specific sid-effects have been described after combined
      therapy with calcipotriol and UV. We describe 3 patients, who in the summer of
      1993, after a combined treatment of calcipotriol and heliotherapy, developed
      hyperpigmentation in the site where the ointment had been applied.
      Hyperpigmentation healed spontaneously in less than 7 months. To the best of our
      knowledge there are no other reports of this side-effect due to calcipotriol. In
      our opinion the fact that the 3 patients presented the hyperpigmentation only on
      the treated lesions and that, in the past, they had not presented similar lesions
      after exposure to sunlight confirms the relationship between the
      hyperpigmentation and the combined treatment used.

PMID- 8578957
TI  - Mucocutaneous fungal colonization in HIV-infected children.
AB  - The prevalence of symptomatic mucocutaneous candidiasis in HIV-infected children
      is well documented. Information, however, of the carriage rate of potential
      fungal pathogens is lacking. In this study we determined the fungal colonization
      rate of multiple mucocutaneous sites from 13 HIV-infected and 12 control
      children. The rate of yeast and mould colonization and the species of fungal
      isolates were essentially the same for both groups of patients. However, several
      HIV-infected children asymptomatic for thrush proved to be colonized by Candida
      albicans, and disseminated colonization with Trichosporon beigelii occurred in
      one HIV-infected child. All cultures for dermatophytes were negative. While the
      carriage rate with fungi other than C. albicans was not increased in the HIV
      infected group, the isolates recovered are known pathogens in the
      immunocompromised host and the colonization of these organisms may be a potential
      source of infection.

PMID- 8578958
TI  - HPV infection in male partners of women with squamous intraepithelial neoplasia
      and/or high-risk HPV.
AB  - In order to estimate the prevalence of HPV infection in male partners of women
      with squamous intraepithelial lesions and/or high risk HPV, we examined 25 men.
      In situ hybridisation or polymerase chain reaction was used to detect HPV DNA in
      biopsied tissue or cell samples from the genital epithelium. Twenty (80%) of the
      male consorts had clinical features suggestive of HPV infection. Of these, 18
      (90%) had detectable HPV DNA, 11 (65%) of the high risk type. In 9 cases HPV DNA
      was detected by in situ hybridisation and in 9 by polymerase chain reaction.
      Concordance between female and male HPV type was found in 8 cases (32%), but
      regarding high-risk HPV carriage as such, 10 (40%) couples corresponded. A search
      for HPV infection in male partners of women known to be infected with high-risk
      HPV seems worthwhile.

PMID- 8578959
TI  - Antibodies to the 90 kDa heat shock protein in chronic plaque psoriasis.

PMID- 8578960
TI  - Prostaglandin E1 improves necrobiosis lipoidica.

PMID- 8578961
TI  - Acquired multiple cavernous hemangiomas of the hand.

PMID- 8578962
TI  - LEOPARD syndrome associated with steatocystoma multiplex and hyperelastic skin.
      Report of a Japanese case.

PMID- 8578963
TI  - Cyclosporin A in metastatic Crohn's disease.

PMID- 8578964
TI  - Multiloculated lentigo maligna melanoma in a patient without evidence for
      xeroderma pigmentosum.

PMID- 8578965
TI  - Erythema gyratum repens-like eruption in a patient with Sjogren syndrome.

PMID- 8578967
TI  - Very low-dose chloroquine treatment for porphyria cutanea tarda.

PMID- 8578968
TI  - Could bacterial acetaldehyde production explain the deleterious effect of alcohol
      on skin diseases?

PMID- 8578969
TI  - Diffuse palmoplantar keratoderma associated with acrocyanosis and livedo
      reticularis. Two sporadic cases.

PMID- 8578966
TI  - Cutaneous alternariosis occurring in a patient treated with local intrarectal
      corticosteroids.

PMID- 8578970
TI  - Pseudoallergic hepatitis after a single intake of 10 mg acitretin (Neotigason)
      for treatment of psoriasis pustulosa.

PMID- 8578971
TI  - Microbial carotenoids.
AB  - Carotenoids occur universally in photosynthetic organisms but sporadically in
      nonphotosynthetic bacteria and eukaryotes. The primordial carotenogenic organisms
      were cyanobacteria and eubacteria that carried out anoxygenic photosynthesis. The
      phylogeny of carotenogenic organisms is evaluated to describe groups of organisms
      which could serve as sources of carotenoids. Terrestrial plants, green algae, and
      red algae acquired stable endosymbionts (probably cyanobacteria) and have a
      predictable complement of carotenoids compared to prokaryotes, other algae, and
      higher fungi which have a more diverse array of pigments. Although carotenoids
      are not synthesized by animals, they are becoming known for their important role
      in protecting against damage by singlet oxygen and preventing chronic diseases in
      humans. The growth of aquaculture during the past decade as well as the
      biological roles of carotenoids in human disease will increase the demand for
      carotenoids. Microbial synthesis offers a promising method for production of
      carotenoids.

PMID- 8578972
TI  - Chromatography in the downstream processing of biotechnological products.
AB  - Chromatography techniques are essential for the isolation and purification of
      most of the high value products of modern biotechnology. The economically
      sensible and technically satisfactory downstream processing of a therapeutic
      protein, usually involves a number of chromatographic steps. Its development and
      optimization require considerable knowledge of the various physico-chemical and
      engineering aspects of biochemical chromatography. This review addresses the
      various modes of chromatography and the design of chromatographic separation
      processes from a biotechnologist's point of view. Strategies for optimizing the
      structure of the downstream process are outlined and scaling up consideration are
      discussed. The importance of the different chromatographic methods in research
      and development is estimated in an analysis of protein purification schemes
      recently published in the literature. Finally, examples of the application of
      chromatographic procedures for process scale product purification in the
      biotechnological industry are given.

PMID- 8578973
TI  - Production of rhamnolipid biosurfactants.
AB  - Biosurfactants are of increasing interest due to their broad range of potential
      applications. A large variety of microbial surfactants is known at present, some
      of which may be used for specific applications. Towards the large scale
      industrial production of biosurfactants, the physiology, biochemistry and
      genetics of biosurfactant synthesis has to be well understood. A fully integrated
      process has to be developed, allowing high productivities under optimized
      conditions. In the past few years, we have investigated the molecular biology of
      rhamnolipid biosynthesis have been partially purified and characterized. The
      structural and regulatory genes encoding the rhamnolipid synthesis pathway have
      been isolated and characterized. The knowledge of the complex mechanisms involved
      in rhamnolipid synthesis facilitates the overproduction of these extracellular
      compounds. Furthermore, the transfer of the relevant genes into other species
      allows the production of rhamnolipids in heterologous hosts under controlled
      conditions. An integrated process for the production of rhamnolipids on an
      industrial scale has been developed. This process involves continuous cultivation
      under optimized media and growth conditions and makes use of refined methods of
      cell recycling, gas exchange and downstream processing, thus allowing high yields
      and productivities.

PMID- 8578974
TI  - Overview: bridging basic science and clinical medicine.

PMID- 8578975
TI  - Veterinary medical specialization.

PMID- 8578976
TI  - Standards for veterinary clinical trials.

PMID- 8578977
TI  - Benefits and burdens: legal and ethical issues raised by veterinary
      specialization.

PMID- 8578978
TI  - Estimating disease prevalence with health surveys and genetic screening.

PMID- 8578979
TI  - Thyroiditis--a model canine autoimmune disease.

PMID- 8578980
TI  - [A case of heterochronic bilateral renal infarction].
AB  - A 57-year-old man was admitted with aching pain in his left frank. Left renal
      infarction was revealed by CT scan and arteriogram. Intra-arterial thrombolytic
      therapy was performed, and resulted in a recanalization of the occluded artery
      and elimination of frank pain, but residual stenosis was recognized. At 27 hours
      after the onset of left renal infarction, in spite of the systemic anti-coagulant
      and thrombolytic therapy to prevent the recurrence of the thrombosis, right renal
      infarction occurred. Immediate intra-arterial thrombolytic therapy for right
      renal infarction was performed successfully. Subsequently the serum creatinine
      level increased from 0.8-0.9 to 1.2-1.3 mg/dl due to the functional loss of the
      left kidney, which was confirmed by follow-up renoscintigraphy. Conservative
      intra-arterial thrombolytic therapy seems to be the most effective treatment for
      renal infarction, but left renal salvage failed due to the prolonged time of
      occlusion and residual stenosis. Also, catheterization for diagnosis and therapy
      or thrombolytic therapy itself may induce an additional infarction.

PMID- 8578981
TI  - [A case of soft renal calculi with xanthogranulomatous change].
AB  - A case of soft renal calculi with xanthogranulomatous change is reported. A 37
      year-old female visited our hospital on February 4, 1992 complaining of frequency
      of urination and right lower abdominal pain. Under the clinical diagnosis of
      right renal calculi, extracorporeal shock wave lithotripsy was attempted, but no
      sign of destruction was observed. Right pyelolithotomy was performed on June 8,
      1992. Several soft calculi were removed from the right renal pelvis. Microscopic
      examination showed that the calculi were surrounded by a cell layer including
      foam cells and giant cells. In addition, the calculi revealed positive reaction
      by several stainings (alcian-blue, PAS and muticarmin), which showed that the
      calculi were mainly composed of mucopolysaccharides. We discussed this disease in
      terms of symptoms, diagnosis, treatment and mechanism in comparison with previous
      reports.

PMID- 8578982
TI  - [Usefulness of the 24-hour delayed film of upper gastrointestinal series for the
      diagnosis of sigmoidovesical fistula: report of 3 cases].
AB  - Recently, sigmoidovesical fistula is not a rare disease as a result of the change
      of our food style and increase in the age ratio. However, in general, the
      preoperative image diagnosis is difficult. We have experienced three cases of
      sigmoidovesical fistula, examined by barium enema, cystography, upper
      gastrointestinal series, cystoscopy, colonic fiberscopy and computed tomography.
      The fistulas were identified preoperatively by the 24-hour delayed film of upper
      gastrointestinal series. By this method, the regions of sigmoidovesical fistula
      were identified, and the patients were operated. We concluded that the 24-hour
      delayed film in upper gastrointestinal series might be useful to diagnose the
      sigmoidovesical fistula.

PMID- 8578983
TI  - [A case of testicular tumor associated with the contralateral undescended
      testis].
AB  - A 36-year-old man visited the hospital complaining of painless swelling of the
      right scrotal contents. His left scrotal contents were absent in the scrotum.
      Right inguinal orchiectomy was performed on May 17, 1993 under the diagnosis of
      testicular tumor. The pathological diagnosis of the tumor was pure seminoma.
      Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed
      the enlargement of para-aortic lymph nodes and there was a soft tissue signal in
      the left inguinal region which seemed to be the left testis in MRI. His serum
      testosterone level was low and gonadotropin level was high. The left orchiopexy
      was performed on June 24, 1993, but the left testis was finally removed because
      of methicillin-resistant Staphylococcus aureus (MRSA) infections. Radiation
      therapy was done against the metastatic lesion in the retroperitoneal lymph nodes
      and complete remission was obtained. The left undescended testis pathologically
      showed atrophy of germ cells but there was no appearance of atypia of Leydig
      cells or germ cells.

PMID- 8578984
TI  - [Study on the pathological grade in the primary and distant metastatic lesions of
      renal cell carcinoma].
AB  - We studied the pathological features of renal cell carcinoma focusing on the
      changes of grade in the primary and metastatic lesions. The subjects consisted of
      46 patients who received both nephrectomy and excision of distant metastatic
      lesions. As to the grade of metastatic lesions assessed according to the grade of
      primary lesion, over 40% of metastatic lesions did not coincide with the primary
      lesion except for grade I. In the study on the grade in each metastatic organ, as
      to lung metastasis, the rate of low grade malignancy (grades I and II) was 84.6%,
      and the same tendency was observed in the spleen (85.7%), adrenal gland of the
      affected side (71.4%), liver (100%) and brain (66.7%). On the other hand, as to
      the osseous metastasis, the rate of high grade malignancy (grades III and IV) was
      87.5%, and the same tendency was observed in the contralateral adrenal gland
      (100%) and bladder (100%). We conclude that a lower grade clones as well as
      higher grade clones in the primary lesion must be analyzed to elucidate the
      metastasis of renal cell carcinoma.

PMID- 8578985
TI  - [Analysis of 42 patients with renal trauma--radiographic assessment of surgical
      application].
AB  - We treated 42 patients with renal trauma between 1988 and 1994. There were 18
      cases of renal contusion, 12 of minor laceration, 6 of major laceration, 5 of
      renal rupture and 1 of major laceration with pedicle injury. Thirty-two patients
      were treated by conservative management, 10 were treated surgically, 9 by simple
      nephrectomy and 1 by partial nephrectomy. Excretory urography was performed in 27
      patients. For stage evaluation, these cases were classified into 4 groups. I: The
      renal pelvis and calices were clearly enhanced. II: The renal pelvis was enhanced
      but part of the calix was not. III: The renal pelvis was not clearly enhanced and
      only some calices were enhanced. IV: The renal pelvis and calices were
      unenhanced. In addition, computerized tomography was carried out in 24 patients.
      We believe that cases with classification as III or IV in excretory urography,
      incomplete enhancement by computerized tomography, and recognized extravasation
      should be treated operatively.

PMID- 8578986
TI  - [Epidemiological study of risk factors for bladder cancer].
AB  - A case-control study was conducted on 303 male bladder cancer patients and
      controls. General population controls were chosen from 15 areas in Gunma
      Prefecture and were matched by age (+/- l y.o.) to the subjects. Age-adjusted and
      smoking-adjusted odds ratio (O.R.) and a 95% confidence interval (C.I.) were
      calculated for each item. Risk factors for bladder cancer in men were
      investigated. The O.R. tended to be significantly higher for those who had
      history of smoking, who smoked more per day, who had smoked longer, whose
      Brinkman index was higher, who began smoking younger and who inhaled deeper than
      it was for non-smokers. O.R.s of having a past history or complication of
      cystitis (age-adjusted) and benign prostatic hypertrophy (age- and smoking
      adjusted) were significantly higher, but the difference was supposed to be caused
      by bias. There was a significantly lower age- and smoking-adjusted O.R. for
      bladder cancer in men who engaged in sales, whose blood type was O, who drank
      milk frequently, who ate grains frequently, who age vegetables frequently and who
      had a past history or complication of hypertension. The number of cases and
      controls with first degree family members who developed cancer respectively
      supposed to be highly related to smoking, were as follows; 16 and 8 for lung
      cancer, 3 and 0 for larynx cancer and 6 and 3 for bladder cancer. The following
      characteristics failed to show any significant difference between subjects with
      bladder cancer and the control group; height and weight now and 20 years ago,
      jobs which deal with dye, academic career, marriage, number of children, alcohol
      drinking and the use of hair dye or analgesics.

PMID- 8578987
TI  - [Experience with one stage repair of hypospadias and chordee without hyposradias
      using free graft of prepuce].
AB  - We treated 14 patients with moderately severe hypospadias and chordee without
      hypospadias using a free graft of prepuce by a modified Devine-Horton technique,
      between September 1993 and April 1995. There were 12 primary cases and 2
      secondary cases in which prior operations had already been done. Four (33%) of
      the primary cases required a second procedure; 3 for urethrocutaneous fistula and
      1 for urethral shrinkage. Both of the secondary cases needed further procedures;
      1 for meatal stenosis and 1 for urethral stricture and diverticula. Although the
      need for reoperation is unfortunately high, six of the 7 recently treated
      patients experienced no complications. Thirteen of the 14 patients (93%) achieved
      excellent functional and cosmetic results with 1 or 2 procedures. We believe the
      use of free grafts allows a better functional and cosmetic outcome because the
      secondary torsion and bulkiness of the penile shaft caused by a vascular pedicle
      are eliminated.

PMID- 8578988
TI  - [Evaluation of sexual function in adults with myelomeningocele].
AB  - In the present study, sexual function in 46 patients (22 males and 24 females)
      with myelomeningocele was assessed by a questionnaire study. The mean age of the
      patients was 24.0 +/- 9.6 years (with an age range of 18 to 50) for male patients
      and 25.2 +/- 6.2 years (with an age range of 18 to 42) for female patients.
      Having interest in the opposite sex and sexual desire were evident in 95% and
      100% of male patients, and 83% and 75% of female patients, respectively. In male
      patients, erection was achieved in 95% by visual stimulation and in 86% by
      tactile stimulation. However, only 27% of the patients with erectility were
      satisfied with penile rigidity. Ejaculation and orgasm was noted in 67%. Orgasm
      was frequently seen in patients whose external sphincter activity was maintained.
      The age and the degree of lower extremity paralysis according to Sharrard
      classification were not significantly correlated with sexual function. In female
      patients, menstruation was regular in 95%, vaginal secrete was adequate in 88%,
      but only 19% of the patients felt ecstacy around perineal lesion at coital
      movements. In female patients, sexual function was not correlated with the age,
      the degree of lower extremity paralysis and detrusor activity-sphincter activity.
      Although most patients had sexual desire, only 18% of the males, and 33% of the
      females, had sexual intercourse activities. It appears, therefore, that these
      patients need to be given appropriate advice.

PMID- 8578990
TI  - [Retroperitoneal leiomyoma: a case report].
AB  - The patient was a 40-year-old woman who was hospitalized for edema of whole body.
      On admission, ultrasonography, CT scan and MRI revealed bilateral hydronephrosis
      due to retroperitoneal large tumors. The angiography showed hypervascular tumors
      in the pelvis. These tumors were surgically removed and the histology was
      leiomyoma. The retroperitoneal leiomyoma is rare and only 16 cases have been
      reported in the literature besides our patient.

PMID- 8578989
TI  - [Primary malignant lymphoma of the adrenal gland: a case report].
AB  - A 65-year-old woman visited our hospital complaining of general fatigue and
      nausea. CT scan revealed a homogeneous mass in the left adrenal gland, which was
      seven centimeters in diameter. Mild swelling of the right adrenal gland was also
      suspected. We failed to find the primary tumor, although a metastatic non
      functioning adrenal tumor was suspected. Adrenalectomy was performed under the
      diagnosis of a non-functioning adrenal tumor. Pathological examination showed a
      non-Hodgkin's lymphoma. Since a bleeding tendency gradually developed following
      the operation, a bone marrow biopsy was done, revealing an invasion by tumor
      cells. Patients with a malignant lymphoma involving the bone marrow should not be
      operated on because fatal complications may develop postoperatively. A malignant
      lymphoma should be considered as a possible diagnosis of adrenal tumors, although
      it is very rare.

PMID- 8578991
TI  - [Double cancers of renal cell carcinoma and testicular seminoma: a case report].
AB  - A case of metachronous presentation of renal cell carcinoma and testicular
      seminoma is reported. A 48-year-old man underwent left radical nephrectomy for a
      renal tumor on September 4, 1991. Pathological examination revealed clear cell
      carcinoma with no capsular penetration. There was no evidence of distant
      metastases. During postoperative follow-up, he noticed a painless left testicular
      induration in July, 1994. Serum human chorionic gonadotropin beta subunit as a
      tumor marker was elevated. Left radical orchiectomy was performed on October 17,
      1994. Pathological examination revealed an anaplastic seminoma localized within
      the testis. Chest X-ray was normal and CT of the abdomen demonstrated no evidence
      of retroperitoneal lymphadenopathy. The patient was diagnosed as clinical stage I
      left testicular seminoma. He was free of disease 8 months postoperatively.
      Including our case, 15 cases of clinically detected double cancers of renal cell
      carcinoma and testicular germ cell tumor have been reported worldwide. This is
      the first case of a metachronous presentation of these two cancer types preceded
      by renal cell carcinoma.

PMID- 8578992
TI  - Detection and isolation of nepoviruses on strawberry in the Czech Republic.
AB  - Arabis mosaic, strawberry latent ringspot, tomato black ring and raspberry
      ringspot nepoviruses were monitored using double sandwich enzyme-linked
      immunosorbent assay (DAS-ELISA) in 18 cultivars of strawberry Fragaria x ananassa
      Duch. in the Czech Republic. Arabis mosaic and strawberry latent ringspot viruses
      were detected, isolated and characterized on differential host plants and by
      electron microscopy. Both viruses were purified and antisera to them were
      prepared.

PMID- 8578993
TI  - Increased effects of topically applied interferon on herpes simplex virus-induced
      lesions by caffeine.
AB  - Caffeine (Cf, 0.15-0.6 mg/ml) and human leukocyte interferon (IFN, > 5 x 10(2)
      IU/ml) partially inhibited the replication of herpes simplex virus type 1 (HSV-1)
      in human diploid LEP cells and HaCaT cells. When the two drugs were applied
      simultaneously the inhibitory effects exceeded those achieved with either
      substance alone. In the subsequent clinical trial, which was conducted as a one
      center, randomised, and placebo-controlled study, the same substances included in
      either ointment or solution were used for topical treatment of recurrent herpetic
      lesions. Of 115 patients taken into the study 20 were treated with Cf only (50
      mg/g of ointment or solution), 25 with IFN only (5 x 10(4) IU/g), 25 with mixture
      of Cf and IFN (same concentrations) and 45 with placebo. Both the healing time
      (HT, period between the prodromes and reepithelization) and the spreading time
      (ST, period between the prodromes and the appearance of the last new lesion) were
      recorded in each patient. While the placebo effects were negligible, the other
      treatments tended to abort the lesions. HT was shortened by at least 4 days in
      75% of patients treated with Cf alone, in 88% of those treated with IFN alone,
      and in all patients treated with their mixture. The effects on ST were less
      marked; in the case of Cf alone they were negligible. A shortening of ST by at
      least 2 days was recorded in 40% and 60% of patients treated with IFN alone and
      the drug mixture, respectively. Statistical analysis confirmed that both in terms
      of HT and ST the disease was more significantly alleviated by the mixture of Cf
      and IFN than by either drug alone.

PMID- 8578994
TI  - Characterization of the alfalfa mosaic virus strain T6.
AB  - A strain T6 of alfalfa mosaic virus (AlMV) was characterized. It was isolated
      from field grown lucerne. Purified virus preparations contained four types of
      particles, B, M, Tb and Ta, containing separately encapsidated ssRNAs 1 to 4. The
      strain T6 was able to infect 40 different plant species of 9 families, and to
      develop a systemic infection in most of them. The symptomatology on bean and the
      RNA mobility of the AlMV strains T6 and 425 were compared. The classical cross
      protection experiments on bean have shown that plants inoculated with strain 425
      did not develop symptoms of the challenge strain T6.

PMID- 8578995
TI  - Replication of a Mamestra brassicae nuclear polyhedrosis virus in a newly
      established Mamestra brassicae cell line.
AB  - A continuous cell line, designated MbL-3, was newly established from minced
      neonate larvae of the cabbage armyworm, Mamestra brassicae. This new cell line is
      heteroploid, containing triploid cells predominantly at the frequency of about
      50%. Doubling time of the cell population is 33 hrs. The Akutsu isolate of a
      Mamestra brassicae nuclear polyhedrosis virus (MbNPV) was examined for
      replication in 16 continuous cell lines, including the cell line MbL-3, from
      seven lepidoptera species: Mamestra brassicae, Pseudaletia separata, Spodoptera
      exigua, Spodoptera frugiperda, Spodoptera littoralis, Spodoptera litura and
      Plutella xylostella. Of these cell lines, only the MbL-3 cells supported a high
      replication of the virus. Four other Mamestra cell lines and a P. separata cell
      line showed a low virus-susceptibility, while the other cell lines were not
      permissive for the virus infection. Maximum infection rate of MbL-3 cells to the
      Akutsu isolate was 23.4%. The growth kinetics of this virus isolate in MbL-3
      cells showed that the virus was released from infected cells 24 hrs p.i. and
      reached a maximal titer 96 hrs p.i. The number of polyhedral inclusion bodies
      (PIBs) reached a maximum of 10(7.5) PIBs/ml 120 hrs p.i.

PMID- 8578996
TI  - Growth and cytopathic effect of Japanese encephalitis virus in astrocyte-enriched
      cell cultures from neonatal mouse brains.
AB  - Neuron-free, astrocyte-enriched brain cell cultures from newborn mice could be
      infected with Japanese encephalitis virus (JEV) as evidenced by
      immunofluorescence (IF), viral replication and cytopathic effect (CPE). Virus
      specific cytoplasmic fluorescence was detectable in astrocytes first after 18
      hrs, released infectious progeny virus in the culture fluid after 24 hrs, and CPE
      after 11 days post infection (p.i.).

PMID- 8578997
TI  - Primase activities constantly present in avian myeloblastosis virus core
      isolates: detection and basic characteristics.
AB  - RNA-synthesizing activities (RNA-SAs) by its nature identical with primase
      activities (Pr-As) were found to be constantly present in avain myeloblastosis
      virus (AMV) core isolates. Their endogenous templates are molecules of the virus
      core-bound host cell DNA (AMV DNA) (Riman and Beaudreau, 1970) that have been
      recently recognized as a collection of still active early replicative structures
      (Riman et al., 1993b). Like the Pr-As, the RNA-SAs are not inhibited by alpha
      amanitin nor by aphidicolin and they show a mutually competitive affinity for ATP
      and GTP. Their reaction products treated with DNase I are short RNAs similar in
      length to initiator RNAs (iRNAs), their precursors and degradation products. In
      AMV core proteins separated in isopycnic CsCl gradients, they are chiefly located
      in the density region of reverse transcriptase activities (RT-As) but with a
      distinct peak fraction. Like Pr-As, they are able to use poly(dT) as template and
      to form, in the presence of [alpha-32P]ATP, products that after DNase I treatment
      consist of poly(rA) molecules similar in length to iRNA monomers and multimers.
      Like the Pr-As, they are able to complement E. coli DNA polymerase (pol) I
      reactions. They occur in the analyzed AMV core proteins as six distinct
      sedimentation species (PrA-SS). This, together with other relevant properties,
      indicates the presence of Pr-As associated with molecules of a primase-alpha DNA
      polymerase enzyme complex, its degradation products and 'free' primase monomers.

PMID- 8578998
TI  - Immune response in mice infected with the attenuated Japanese encephalitis
      vaccine strain SA14-14-2.
AB  - We characterized protective immune response in mice infected with the attenuated
      Japanese encephalitis virus (JEV) strain SA(A) derived from the live JE vaccine
      strain SA14-14-2. In the sera of mice infected with SA(A), antibodies to JEV
      envelope (E) and non-structural NS1 proteins were detected by Western blot
      analysis and neutralization, haemagglutination-inhibition (HAI), and complement
      fixation (CF) antibodies were detected by serological tests. Production of
      antibody to NS1 protein strongly indicated peripheral growth of SA(A) in mice and
      its growth induced the immune response. A single immunization with SA(A)
      significantly protected mice against lethal intracerebral (ic) challenge with the
      virulent SA(V) strain.

PMID- 8578999
TI  - Nucleotide sequence of the protein E gene of the tick-borne encephalitis virus
      strain 595 isolated in Slovakia.
AB  - Tick-borne encephalitis (TBE) virus, strain 595 was isolated from Ixodes ricinus
      ticks in southern Slovakia. A part of the protein E gene was sequenced and
      compared with the prototype strain Neudorfl. Seventeen silent mutations and two
      amino acid changes (Ile-->Val, residue 167; Asn-->Thr, residue 366) were found.
      The nucleotide homology in the sequenced part of protein E gene of the strain 595
      and the prototype strain Neudorfl is 98.6%. These findings indicate that the
      strain 595 is closely related to the strain Neudorfl.

PMID- 8579000
TI  - Influenza virus M2 protein and haemagglutinin conformation changes during
      intracellular transport.
AB  - The influenza virus M2 protein has an ion channel activity that permits ions to
      enter the virion during its uncoating and also modulates pH of intracellular
      compartments. M2 protein is a homotetramer consisting of either a pair of
      disulfide-linked dimers or a disulfide-linked tetramer. The M2 trans-membrane
      domain peptide adopts an alfa helical secondary structure. In polarized cells, M2
      protein is expressed at the apical cell surface. The amantadine-induced, M2
      mediated conversion of influenza A virus haemagglutinin (HA) to the low pH
      conformation occurs in an acidic trans-Golgi compartment. The M2 protein ion
      channel activity can affect the conformation of cleaved HA during intracellular
      transport. The equine influenza virus 1 HA expressed from cDNA does not require
      coexpression of a functional M2 protein to maintain HA in its native
      conformation.

PMID- 8579001
TI  - R-subtype of early antigen of the Epstein-Barr virus in the diagnostics of the
      chronic form of infectious mononucleosis.

PMID- 8579002
TI  - [Bee venom immunotherapy: whom to treat with which regiment for how long?].

PMID- 8579003
TI  - Unusual course of the hepatitis C virus infection in one patient diagnosed of
      common variable immunodeficiency.
AB  - Common variable immunodeficiency (CV1) is defined by low serum IgG and IgA
      levels, and it is the second most frequent primary immunodeficiency. The
      indication for treatment with human gammaglobulin in patients with this syndrome
      has been well established. Here we report a case history of a patient diagnosed
      of common variable immunodeficiency, and she had treatment with i.v. commercial
      gammaglobulin. In the course of the disease, she developed symptoms that make us
      think about the possibility of hepatitis virus infection. HBV-associated antigens
      and antibodies, and HCV-Ab were all negative. So, amplification of HCV-RNA by
      polymerase chain reaction (PCR) was performed, and it became positive in two
      different determinations. Liver failure got worse quickly and the patient died.
      About the course of the HCV infection, only 30% of patients with acute hepatitis
      get biochemical resolution, and 50-70% become carriers and have persistent
      chronic hepatitis or active chronic hepatitis. In this case, HCV infection showed
      an unusual acute and fatal course, it is possible that the impaired immune status
      of the patient could play a role in the acute course of the disease. Therefore,
      every patient who have intravenous immunoglobulin replacement must be monitored
      regularly for liver function tests, and by PCR for HCV infection.

PMID- 8579004
TI  - [Bronchiolitis obliterans in the child].
AB  - Bronchiolitis obliterans (BO) is an unusual illness; however it has increased in
      the last few years. In children it is usually postinfectious, and it is caused by
      different agents, and it is considered as a long term sequelae of viral
      infection. BO is suspected when respiratory signs and symptoms persist after a
      pulmonary infection, mainly viral. The prognosis depends on an early diagnosis.
      BO may lead to pulmonary fibrosis or COPD. The response to treatment is
      successful in the early stage of disease. It is necessary to follow children with
      viral pulmonary infection, doing pulmonary function tests, arterial blood gases
      and spirometry.

PMID- 8579006
TI  - Venom immunotherapy: tolerance to a 3-day protocol of rush-immunotherapy.
AB  - In the last 10 years in the Ramon y Cajal Hospital, in Madrid, we have treated 78
      patients who had presented anaphylactic reactions after hymenoptera stings, by
      means of a rush immunotherapy protocol. Fifty patients received wasp venom and 30
      received honeybee venom (2 patients were treated with both venom types). Venom
      immunotherapy is given to out-patients, at the hospital, in the morning. The
      interval between injections administered on the same day is 30 minutes and the
      patient stays for 2 hours under observation after the last daily dose. The
      schedule we use is as follows: Day 1 (0.05-1-5-10 micrograms of venom), Day 2 (20
      40 micrograms), Day 3 (40-60 micrograms), Day 5 (100 micrograms). Afterwards,
      they receive 100 micrograms after 2 weeks and, finally, monthly. In order to
      achieve a better tolerance, patients are protected with antihistamines on the
      days they are administered the immunotherapy (mequitazine 5 mg every 12 hours)
      and also, doses equal or over 40 micrograms are given fractionally, injecting
      half dose in each arm. The percentage of systemic reactions (mild or moderate) is
      13.3% for patients treated with honeybee venom and 2% for patients treated with
      wasp venom. These percentages are lower than those obtained with conventional
      protocols in which it takes several weeks to reach the maintenance dose. The
      speed and convenience of this protocol and also its appropriate safety have led
      us to use it as a routine treatment for patients who require venom immunotherapy
      after suffering anaphylactic reactions due to hymenoptera stings.

PMID- 8579005
TI  - [Blocking antibodies in Dermatophagoides allergy].
AB  - A group of patients with Dermatophagoides allergy was estudy analyze the behavior
      of blocking antibodies (Ab E: total IgG, IgG1 and IgG4) directed against complete
      allergen extract (CE) and against the major allergens, Der pI and Der pII, and
      its relation with the clinical results of desensitizing treatment. A group of 36
      patients received specific immunotherapy (IT) and conventional treatment alone.
      Over a 12-month period, four follow-up studies were made to evaluate the
      patient's clinical situation (symptom score) and to determine total IgG and IgG
      subclasses directed against CE, DER pI, and DER pII. In the group treated with
      IT, the levels of all IgG subclasses increased subjectively, but in the group
      without It, igG levels did not change. There was no significant improvement in
      ocular on pulmonary symptoms in either group. Nasal symptoms had a more favorable
      evolution in the IT group.

PMID- 8579007
TI  - Quantitative determination of fibronectin (FN): evaluation of immunoturbidimetric
      and rate nephelometric techniques for FN assay in the different biologic
      materials.
AB  - Aim of this study is to determine fibronectin concentration in the different
      biological materials to study its changes in the anatomic districts where the
      cell interactions in which FN participates do occur. The traditional
      immunoturbidimetric method and the nephelometric method are compared. An
      alternative method using a support for the collection of very small samples is
      proposed and the results obtained are discussed. This approach with solid phase
      immunonephelometry can be used both in amounts of biological fluids too small for
      traditional methods and in concentrations < 4.5 mg/dL. It is hoped that less
      complex techniques will be studied, allowing routine tests that can be performed
      by all laboratories. Unfortunately, at present this method is still investigated,
      however, it would be useful to adopt it in case of difficult sample collection.

PMID- 8579008
TI  - H1-antihistamines and prescription compliance.
AB  - H1-antihistamines (H1A) have been used for more than 50 years in the treatment of
      allergic pathology. Their widespread consumption and the growing pharmaceutical
      offer is noteworthy. Despite this, we have not found any study on the compliance
      of these drugs in the scientific literature reviewed. The aims of this study are
      to evaluate compliance with the prescription of H1A in a sample of allergic
      patients diagnosed as pollen rhinoconjunctivitis (PRC), and to evaluate the
      possible association between the degree of compliance and certain patient
      dependent parameters (age, sex, cultural level, knowledge of the prescription and
      treatment [duration, number of drugs, posology, method of administration and
      appearance of adverse drug reactions]). The sample size was 300, and 164 were
      attended. Of these 164 patients, 123 claimed to have taken correctly the H1A
      prescribed by the allergologist. Of the group of patient claiming to have
      followed treatment correctly, only 8 patients did not remember the number of
      packs of H1A bought, nor their price, nor the appearance of the tablets (or
      solution). Regarding the frequency of use, 101 patients took the H1A daily, and
      the remaining 22, depending on symptoms. Administration of the H1A was always
      oral-tablets in 114 cases and solution in 9. The compliance we have found is at a
      medium level, similar to that reported in other studies (although on other
      drugs), and no significant differences were found in relation to the parameters
      studied.

PMID- 8579009
TI  - [Cockroach allergy: a study of its prevalence using skin tests with commercial
      extracts].
AB  - Cockroaches have been increasingly recognized as an important source of indoor
      allergens. In this study we assessed the prevalence of cockroach sensitization
      among an outpatient population observed at our Department (155 patients with a
      mean age of 29 +/- 12 years), based on skin "prick" tests with four commercial
      cockroach extracts along with a common battery of standardized inhalant
      allergens. We found a positive wheal to at least one of these four extracts in 27
      patients: 26 (96.2%) to Blatta orientalis, 10 (37%) both to Blatella germanica
      and 1 (3.7%) exclusively to Blatella germanica, with no significant concordance
      between them. We also observed in patients with cockroach positive skin "prick"
      test an association with atopy (p < 0.001) and with cutaneous reactivity to other
      indoor allergens, namely house dust mites (p = 0.02), danders (p = 0.01) and
      fungi (p = 0.01). These data confirm the higher risk of cockroach sensitization
      among the atopic population sensitized to indoor allergens. However, the
      heterogeneity of the positive cutaneous responses obtained in this study,
      possibly reflecting the incomplete standardization of cockroach extracts,
      questions the real prevalence and clinical significance of this particular
      sensitization.

PMID- 8579010
TI  - Sustained-release local hirulog therapy decreases early thrombosis but not
      neointimal thickening after arterial stenting.
AB  - Adventitial heparin delivery has been shown to inhibit thrombosis and neointimal
      thickening in a rat carotid injury model. To determine whether sustained, local
      delivery of hirulog, a potent antithrombin agent, inhibits thrombus formation and
      neointimal thickening after arterial stenting, silicone polymers containing
      hirulog were formulated at a concentration of 5.8% by weight and were tested in
      vitro to determine the rate of drug release. An oversized metallic stent was
      implanted in the carotid artery of 18 juvenile farm pigs. Hirulog-impregnated
      silicone polymers were placed around the adventitial surface of one stented
      segment of each animal and a control polymer was placed contralaterally.
      Intravenous hirulog (4 mg/kg/hr) was infused for the duration of the procedure to
      maintain the activated clotting time of > 300 sec. Ex vivo testing estimated the
      release of hirulog to be 1.54 micrograms/mg matrix/day with no loss of
      anticoagulant activity of the released peptide. In four pigs killed on days 3
      through 5, macroscopic thrombus was very faintly visible on the stent struts of
      one arterial segment treated with sustained-release hirulog but was readily
      evident in all control arteries. However, electron microscopy showed platelet
      adhesion and microscopic thrombus formation on each stent of both treated and
      untreated sides. Fourteen pigs were killed 32 +/- 4 days after stenting.
      Histologic analysis showed no difference between hirulog-treated and control
      sides in the volume of neointima (540 +/- 129 units vs 357 +/- 95 units, p =
      0.27) or in the average intima to media ratio (0.44 +/- 0.12 vs 0.34 +/- 0.24, p
      = 0.47) over the length of the stented segment. Late thrombotic occlusion
      occurred in two hirulog-treated and two control arteries. In this model, local
      adventitial hirulog delivery at the dose and delivery rate used may reduce, but
      does not prevent, thrombus formation and does not reduce the severity of
      neointimal thickening after carotid stent implantation.

PMID- 8579011
TI  - Decreased free radical scavengers with reperfusion after coronary angioplasty in
      patients with acute myocardial infarction.
AB  - Early reperfusion after myocardial infarction improves survival rate and is
      thought to preserve myocardial function, but the reperfusion of ischemic tissue
      may release oxygen free radicals, which could adversely affect left ventricular
      function and diminish the beneficial effects of reperfusion. Measurements related
      to free radical scavenging (plasma and erythrocyte enzyme systems, which are
      involved in free radical control, alpha-tocopherol, selenium, and manganese
      superoxide dismutase) may be indirect markers of free radical production. We
      evaluated 10 patients undergoing coronary angioplasty within 4 hours of
      myocardial infarction to measure the impact of abrupt reperfusion on free radical
      scavenger-related indexes. Pulmonary artery samples were taken before,
      immediately after, and 3 hours after angioplasty. During reperfusion, significant
      reductions occurred in alpha-tocopherol (1.1 +/- 0.3 mg/dl before, 0.9 +/- 0.2
      mg/dl immediately after [p = 0.03], and 0.8 +/- 0.2 mg/dl 3 hours after
      percutaneous transluminal coronary angioplasty [p = 0.02]), and selenium levels
      (13.7 +/- 2.4 micrograms/dl before, 12.9 +/- 2.4 micrograms/dl immediately after,
      and 10.2 +/- 3.0 micrograms/dl 3 hours after angioplasty [p = 0.0006]).
      Erythrocyte markers (glutathione peroxidase and superoxide dismutase) were not
      altered by reperfusion, possibly reflecting the relatively long half-life of the
      erythrocyte. The erythrocyte glutathione peroxidase value before reperfusion in
      patients (30.8 +/- 5.1 IU/gm of hemoglobin) was lower than in a control group
      (36.1 +/- 6.5 IU/gm of hemoglobin; p = 0.01). Thus the decrease in plasma alpha
      tocopherol and selenium after reperfusion in this group of patients may reflect a
      general alteration in plasma free radical scavenger levels, suggesting
      consumption of plasma free radical scavengers with reperfusion after acute
      myocardial infarction.

PMID- 8579012
TI  - Preconditioning ischemia time determines the degree of glycogen depletion and
      infarct size reduction in rat hearts.
AB  - The cardioprotective effect of preconditioning is associated with glycogen
      depletion and attenuation of intracellular acidosis during subsequent prolonged
      ischemia. This study determined the effects of increasing preconditioning
      ischemia time on myocardial glycogen depletion and on infarct size reduction. In
      addition, this study determined whether infarct size reduction by preconditioning
      correlates with glycogen depletion before prolonged ischemia. Anesthetized rats
      underwent a single episode of preconditioning lasting 1.25, 2.5, 5, or 10 minutes
      or multiple episodes cumulating in 10 (2 x 5 min) or 20 minutes (4 x 5 or 2 x 10
      min) of preconditioning ischemia time, each followed by 5 minutes of reperfusion.
      Then both preconditioned and control rats underwent 45 minutes of ischemia
      induced by left coronary artery (LCA) occlusion and 120 minutes of reperfusion.
      After prolonged ischemia, infarct size was determined by dual staining with
      triphenyltetrazolium chloride and phthalocyanine blue dye. Glycogen levels were
      determined by an enzymatic assay in selected rats from each group before
      prolonged ischemia. We found that increasing preconditioning ischemia time
      resulted in glycogen depletion and infarct size reduction that could both be
      described by exponential functions. Furthermore, infarct size reduction
      correlated with glycogen depletion before prolonged ischemia (r = 0.98; p <
      0.01). These findings suggest a role for glycogen depletion in reducing ischemic
      injury in the preconditioned heart.

PMID- 8579013
TI  - Endothelial dysfunction in the early stage of atherosclerosis precedes appearance
      of intimal lesions assessable with intravascular ultrasound.
AB  - The objective of this study was to clarify whether morphologic evaluation of the
      in vivo artery with intravascular ultrasound provides as sensitive a marker as
      endothelial dysfunction or microscopic histologic assessment. Endothelial
      dysfunction assessed with the changes in the vessel diameter during acetylcholine
      infusion has been used as a more sensitive marker of atherosclerosis than the
      angiographic estimates of morphologic structure of the vessel. Recent advent of
      intravascular ultrasound has provided such high-resolution images of the vessels
      that morphologic changes in the vessel structure are sensitively and accurately
      detected. Twenty-two rabbits were divided into three groups: six rabbits fed a
      cholesterol-rich diet for 2 weeks as the hypercholesterolemia group, eight
      rabbits fed with the diet for 8 weeks as the atherosclerosis group, and eight
      rabbits fed a normal diet as the normal group. After evaluating the
      atherosclerotic lesions by intravascular ultrasound, the cross-sectional area was
      measured in the baseline and during the infusion of acetylcholine (0.05, 0.5, and
      5 micrograms/kg/min) and nitroglycerin (5 micrograms/kg/min). No atherosclerotic
      lesions were detectable with intravascular ultrasound in any rabbit despite the
      presence of microscopic intimal lesions in the vessels in the rabbits of the
      atherosclerosis group. The cross-sectional area increased during acetylcholine
      infusion in the rabbits of the normal and the hypercholesterolemia groups. In
      contrast, in the rabbits of the atherosclerosis group, the cross-sectional area
      did not significantly increase during acetylcholine infusion at the rate of 0.5
      microgram/kg/min and even tended to decrease at the rate of 5 micrograms/kg/min (
      3.8% +/- 3.7%, P < 0.05 vs the normal group). Dilating responses to nitroglycerin
      infusion were similar among all three groups. In conclusion, impairment of the
      endothelium-dependent vasodilating response assessed with intravascular
      ultrasound in the in vivo vessel precedes the appearance of echographic
      atherosclerotic findings. Thus intravascular ultrasound, if used in combination
      with drug intervention to assess endothelial function, would provide even more
      accurate assessment of the vessels than conventional intravascular ultrasound
      alone.

PMID- 8579014
TI  - Diagnosis of patent foramen ovale by contrast versus color Doppler by
      transesophageal echocardiography: relation to atrial size.
AB  - To ascertain the factors related to the transesophageal echocardiographic
      diagnosis of patent foramen ovale, the primary echocardiographic data were
      reviewed from 74 patients with that diagnosis. Similar detection rates were
      observed with contrast echocardiography (82%) and color flow mapping (78%), but
      contrast was more sensitive in patients with normal-sized atria (94%) and
      isolated right atrial enlargement (100%) than in those with enlarged left atria,
      all but three of whom had biatrial enlargement (52%) (p < 0.001 by chi-square
      test). Doppler flow mapping was less sensitive for normal-sized atria (66%) than
      for isolated enlarged right atria (81%) and left (bi-) atrial enlargement (96%)
      (p = 0.024). Patent foramen ovale was directly visualized by two-dimensional
      echocardiography in 80%, with close agreement to the size of the color flow jet
      (r = 0.90, delta = 0.1 +/- 0.4 mm); foramen ovale size was related to right
      atrial area (r = 0.31, p = 0.015). Thus both saline contrast and color flow
      imaging are necessary to exclude the diagnosis of patent foramen ovale.

PMID- 8579015
TI  - Last-minute preoperative cardiology consultations: epidemiology and impact.
AB  - To identify clinical predictors of last-minute preoperative cardiology
      consultations and to evaluate the impact of these consultations on patient care,
      we performed a retrospective case-control study including all 166 patients who
      received unscheduled cardiology consultations at the preadmission testing center
      (PATC) of an urban teaching hospital. Control subjects were 166 patients matched
      by date and category of surgical procedure. Significant (p < 0.05) independent
      predictors of last-minute consultations included history of myocardial infarction
      (odds ratio [OR] = 23.7; 95% confidence interval [CI] = 1.5 to 373), history of
      chest pain (OR = 15.3; 95% CI = 3.7 to 62.9), history of chronic obstructive lung
      disease (OR = 5.9; 95% CI = 1.1 to 32.9), prior echocardiography (OR = 3.4; 95%
      CI = 1.2 to 9.8), and age (OR per decade = 1.1; 95% CI = 1.04 to 1.1). Thus among
      patients undergoing elective noncardiac surgery, last-minute preoperative
      consultations are common and are usually precipitated by an abnormal
      electrocardiogram or history of cardiovascular disease. Last-minute consultations
      may be preventable if those patients with risk factors for consultation are
      identified in advance of the preadmission evaluation and referred for elective
      consultation.

PMID- 8579016
TI  - Decline in the rate of hospital mortality from acute myocardial infarction:
      impact of changing management strategies.
AB  - This study examined the profile and management of acute myocardial infarction in
      patients hospitalized in the coronary care unit of Henry Ford Hospital to
      determine risk factors or treatments that best explained a decline in in-hospital
      mortality rates. During the 1980s and early 1990s, many therapeutic advances
      occurred in management of acute infarction. Overall and in-hospital mortality
      were observed also to decline, but little is known about the relation of newer
      treatments to clinical outcome. The study population consisted of 1798 patients
      with a confirmed diagnosis of myocardial infarction. Of these, 982 consecutive
      patients were hospitalized in the coronary care unit of Henry Ford Hospital from
      January 1981 through December 1984 and compared with the 816 consecutive patients
      hospitalized from January 1990 through October 1992. Data on baseline
      demographics, initial clinical features, in-hospital management, and in-hospital
      outcome were compared for the two groups. Logistic regression was used to define
      independent predictors of the improved outcome of the two groups. Demographic
      features of the earlier group were similar to those of the later cohort, with the
      exception of a greater incidence of diabetes and hypertension and a lesser
      incidence of angina and prior heart failure. The occurrence of non-Q wave
      infarction increased from 27% in the earlier to 39% in the later group, whereas
      the magnitude of peak creatine kinase elevation in serum was higher in the later
      group. Medical management differed significantly, with increased use of aspirin,
      thrombolytics, heparin, warfarin, nitrates, and beta-blockers and decreased use
      of antiarrhythmic agents, digoxin, and vasopressors in the later group. Coronary
      revascularization was performed during hospitalization in 6.4% of the earlier
      group of patients and 31.6% of the later group. In-hospital mortality was 14.7%
      in the earlier group and 7.4% in the later group. Multivariate logistic
      regression analysis showed that the difference in mortality between the two
      groups was best accounted for by increased use of beta-blockers, angioplasty, and
      thrombolytics, decreased incidence of cardiogenic shock and asystole, and
      decreased use of lidocaine. In conclusion, the presentation and in-hospital
      management of patients with acute myocardial infarction has changed from the
      early 1980s to the early 1990s. The improved hospital mortality rate may be
      associated with both the expanded use of effective therapies and a more favorable
      in-hospital course, although these are not mutually exclusive.

PMID- 8579017
TI  - Clinical predictors of defibrillation energy requirements in patients treated
      with a nonthoracotomy defibrillator system. The ResQ Investigators.
AB  - Many factors can influence defibrillation energy requirements (DER) in patients
      with a nonthoracotomy defibrillator. No large studies, however, have correlated
      clinical characteristics with the DER. In this study, 124 patients underwent the
      same DER protocol with the identical biphasic waveform, nonthoracotomy lead
      system, and lead configuration. These patients were 63 +/- 12 years old (mean +/-
      SD); 99 were men; the ejection fraction was 0.32 +/- 0.13, and 36 were taking an
      antiarrhythmic medication. New York Heart Association congestive heart failure
      class I was present in 28, class II in 70, and class III in 26 patients. Male sex
      (454 +/- 94 V vs 406 +/- 91 V for female sex) was associated with a significantly
      higher DER (p = 0.02) and an increased risk of a DER > 550 V (p = 0.047). No
      other clinical variable was associated with the DER or a DER > 550 V. In
      conclusion, women tend to have lower DERs than men.

PMID- 8579018
TI  - Impact of defibrillator-can size on defibrillation success with a single-lead
      unipolar system.
AB  - In a study of 11 dogs, we assessed whether the defibrillation energy requirements
      of a single transvenous right ventricular electrode/defibrillator can system
      depended on the can size. We compared the defibrillation threshold obtained with
      65% fixed-tilt biphasic shocks with 20, 40, and 80 ml surface area defibrillator
      cans. The energy was delivered between a right ventricular coil inserted through
      the jugular vein and the can placed in the subcutaneous tissue of the left
      superior chest wall. The testing order of each can size was randomly determined.
      Triplicate defibrillation thresholds were obtained with each can. Despite a
      higher impedance (20 ml 85 +/- 22 ohms vs 80 ml 71 +/- 16 ohms, p < 0.01), the 20
      ml can resulted in a similar defibrillation threshold compared with the 80 ml (20
      ml 7.6 +/- 2.8 J vs 80 ml 7.5 +/- 3.4 J) and the 40 ml cans (20 ml 7.6 +/- 2.8 J
      vs 7.5 +/- 3.4 J). In conclusion, with the unipolar lead system the can size does
      not appear to be a factor limiting defibrillation success. Even a can the size of
      a pacemaker does not appear to significantly affect the defibrillation efficacy
      of this lead system.

PMID- 8579019
TI  - Evaluation and extraction of the Accufix atrial J lead.
AB  - The Accufix (Telectronics Pacing Systems, Englewood, Colo.) atrial active
      fixation pacemaker lead has a preformed J stiff retention wire that can fracture
      and erode through the atrium. We screened 85 patients with digital fluoroscopy
      and detected 18 (21%) lead fractures. Fourteen (16%) leads were successfully
      extracted by percutaneous techniques. The mean time for extraction and placement
      of a new atrial lead was 109 +/- 53 min, and a lead > 1 year old but not in the
      presence of a fracture was associated with a significantly longer extraction
      time. There were two extraction complications. One patient had a fever following
      the extraction, and one patient had a focal sensory deficit 1 week after the
      extraction probably caused by a paradoxical embolus. Standard percutaneous
      extraction tools can be used for successful and safe removal of a fractured
      Accufix lead.

PMID- 8579020
TI  - Changes in transmitral and pulmonary venous flow velocity patterns after
      cardioversion of atrial fibrillation.
AB  - To examine the recovery time of left atrial mechanical function after electrical
      cardioversion of atrial fibrillation, we recorded transmitral flow, pulmonary
      venous flow velocities, and interatrial septal motion during atrial systole
      within 24 hours (16 +/- 5 hours) and 10 days after cardioversion in 25 patients
      with atrial fibrillation, including 6 patients with hypertension, 4 with ischemic
      heart disease, 2 with alcoholic heart disease, 5 with dilated cardiomyopathy, and
      8 with no evidence of underlying heart disease. With the exception of the five
      patients with dilated cardiomyopathy, the peak atrial systolic transmitral and
      pulmonary venous flow velocities, peak first systolic velocity of pulmonary
      venous flow, duration of both atrial systolic waves, and amplitude of the
      interatrial septal motion during atrial systole decreased markedly within 24
      hours after cardioversion and increased 10 days after cardioversion. These
      results suggest that active atrial systolic and relaxant variables obtained from
      transmitral and pulmonary venous flow velocities may reflect left atrial
      mechanical function after cardioversion of atrial fibrillation.

PMID- 8579021
TI  - Shortened hospitalization by means of adjusted-dose subcutaneous heparin for deep
      venous thrombosis.
AB  - Adjusted-dose subcutaneous unfractionated heparin (SC heparin) was used in the
      initial management of deep venous thrombosis (DVT) to allow shortened hospital
      stay. Of 78 patients screened, 41% were eligible and 18 (23%) were enrolled.
      Follow-up venous ultrasound examination was performed 6 weeks after discharge. Of
      enrolled patients, 16 (89%) completed the protocol. Hospital length of stay was 2
      days in protocol patients compared with 5 days for patients receiving
      conventional inpatient heparin with a continuous intravenous infusion (p =
      0.0009). Very high heparin doses (mean 42,000 to 62,000 U daily, given in three
      divided doses every 8 hours) and a median time of 21 hours were required
      initially to achieve a target activated partial thromboplastin time (aPTT) > 55
      seconds. Subsequently many patients had supratherapeutic levels, yet there were
      no bleeding complications. Four patients (25%) did not show improvement at follow
      up ultrasound in spite of aPTTs > 55 seconds after the second injection. Clot
      regression was evident in remaining patients. Hospital cost savings were offset
      partially by the need for time- and labor-intensive outpatient monitoring after
      hospital discharge.

PMID- 8579022
TI  - Echocardiographic predictors of survival after surgery for mitral regurgitation
      in the age of valve repair.
AB  - The objective of this study was to identify echocardiographic and clinical
      predictors of survival after mitral valve surgery when mitral repair is an
      option. In 132 patients undergoing mitral valve repair or replacement for the
      diagnosis of mitral regurgitation, preoperative echocardiograms were analyzed
      quantitatively and reviewed by two independent observers for structural
      abnormalities of the mitral valve. In Cox regression analysis, clinical factors
      such as age (mortality rate ratio [MRR] 1.7/decade, 95% confidence intervals [CI]
      1.1, 2.4), and New York Heart Association class IV (MRR 3.1, 95% CI 1.4, 6.7) and
      echocardiographic factors including morphologic evidence of endocarditis or
      myxomatous disease (MRR 0.3, 95% CI 0.1, 0.7) were significant predictors of
      overall survival, although valve repair itself was not. End-systolic dimensions
      and volumes were not, likely related to the small number of patients with
      markedly increased end-systolic dimensions or volumes (5 patients [4%] with end
      systolic dimension > 5.5 cm, 12 patients [9%] with end-systolic volume index > 60
      ml/m2). New York Heart Association class IV (MRR 2.9, 95% CI 1.3, 6.4), age (MRR
      1.7/decade, 95% CI 1.2, 2.6), and the presence of calcification (MRR 4.6, 95% CI
      1.3, 16.2) were independent predictors of survival in multivariate analysis. In
      this contemporary cohort of patients undergoing repair or replacement for mitral
      regurgitation, factors such as echocardiographically determined cause of disease
      and presence of calcification predicted survival; traditional measurements such
      as end-systolic dimensions and volumes were less predictive, most likely because
      patients underwent surgery before their ventricles became markedly enlarged.
      Clinical factors such as age and functional status remained the most potent
      predictors of survival after surgery for mitral regurgitation.

PMID- 8579023
TI  - Assessment of hemodynamic effects of angiotensin-converting enzyme inhibitor
      therapy in chronic aortic regurgitation by using velocity-encoded cine magnetic
      resonance imaging.
AB  - Long-term treatment with angiotensin-converting enzyme (ACE) inhibitors has
      beneficial effects in patients with chronic aortic regurgitation by reducing left
      ventricular volumes and regurgitant fraction. Velocity-encoded cine magnetic
      resonance imaging can directly measure antegrade (forward stroke volume) and
      retrograde blood flow (regurgitant volume) in the ascending aorta. Velocity
      encoded cine magnetic resonance imaging was used in 9 patients with moderate to
      severe aortic regurgitation (regurgitant fraction 49% +/- 17%) to measure
      regurgitant fraction, regurgitant volume, and forward stroke volume at baseline
      and 3 months after therapy with enalapril (mean dose 29 +/- 13 mg). Ten
      additional patients with aortic regurgitation without any drug therapy served as
      a control group. In the treatment group, systolic blood pressure slightly
      decreased from 132 +/- 20 mm Hg to 121 +/- 14 mm Hg (p = not significant),
      whereas diastolic blood pressure and heart rate (beats per minute) remained
      unchanged. Regurgitant fraction decreased in 6 patients (responders) from 49% +/-
      19% to 39% +/- 20% (percentage change 24% +/- 14%, p = 0.002) and was unchanged
      in 3 patients (nonresponder, 49% +/- 19% vs 51% +/- 16%; p = not significant). In
      the responder group, forward stroke volume increased from 128 +/- 32 ml to 148 +/
      57 ml, whereas regurgitant volume remained unchanged (67 +/- 40 ml vs 65 +/- 51
      ml). At baseline, the responder group had a significant higher total vascular
      resistance than the nonresponder group (998 +/- 538 dyne.sec.cm-5 vs 625 +/- 214
      dyne.sec.cm-5; p < 0.05). With enalapril treatment, total vascular resistance in
      the responder group tended to decrease (891 +/- 576 dyne.sec.cm-5), but slightly
      increased in the nonresponder group (679 +/- 276 dyne.sec.cm-5). The control
      group showed no changes in regurgitant fraction, regurgitant volume, forward
      stroke volume, and total vascular resistance at follow-up.

PMID- 8579024
TI  - New insights into the reduction of mitral valve systolic anterior motion after
      ventricular septal myectomy in hypertrophic obstructive cardiomyopathy.
AB  - To determine the mechanism of reduction of mitral valve systolic anterior motion
      by myectomy, we examined 33 patients with hypertrophic obstructive cardiomyopathy
      echocardiographically before and after myectomy. Measurements included outflow
      tract diameter, the direction of ejection streamline (the angle between the
      ejection flow and the mitral valve), midventricular fractional area change, and
      papillary muscle inward excursion in the short-axis image. After myectomy, the
      outflow tract was enlarged (from 1.2 +/- 0.3 cm to 2.1 +/- 0.4 cm; p < 0.001),
      and the ejection flow became more parallel to mitral leaflets (from 51 +/- 10
      degrees to 28 +/- 8 degrees; p < 0.001), whereas hyperdynamic midventricular
      fractional area change was reduced (81% +/- 14% to 62% +/- 14%; p < 0.001), and
      papillary muscle excursion decreased (1.3 +/- 0.3 cm to 0.8 +/- 0.3 cm; p <
      0.001). Outflow enlargement and reduced ventricular contraction would decrease
      the Venturi force. Change of ejection streamline and reduced contraction would
      decrease the drag force onto the mitral leaflets. Blunted papillary motion would
      increase the mitral leaflet tension and decrease the effect of drag force on both
      leaflets. Thus myectomy decreases Venturi and drag forces and appears to reduce
      systolic anterior motion of the mitral valve.

PMID- 8579025
TI  - In vivo detection of Trypanosoma cruzi antigens in hearts of patients with
      chronic Chagas' heart disease.
AB  - The heart is the most commonly affected organ in chronic Chagas' disease, and
      lymphocytic myocarditis is often observed. However, the pathogenesis of chronic
      Chagas' heart disease is controversial. The purpose of this study was to
      determine whether in vivo T. cruzi antigens could be detected in hearts from
      patients with chronic Chagas' disease and to investigate whether a correlation
      between these antigens and the intensity of myocardial inflammation exists. We
      studied 16 patients with chronic Chagas' heart disease. Ten patients had severely
      impaired left ventricular function and refractory heart failure, and six had
      episodes of sustained ventricular tachycardia without severe left ventricular
      dysfunction. Eight patients underwent magnetic resonance imaging with gadolinium
      enhancement to guide endomyocardial and surgical biopsies to sites with more
      intense inflammatory processes. Myocardial specimens were studied with
      immunohistochemical techniques by using rabbit anti-T. cruzi immune serum to
      detect the presence of T. cruzi antigen. All patients had evidence of some
      myocarditis in at least one myocardial fragment. T. cruzi antigen was detected in
      11 (69%) patients. T. cruzi antigens were detected in 10 (71%) of 14 regions with
      histopathologic evidence of moderate or severe myocarditis. In contrast, T. cruzi
      antigens were detected in 3 of 18 regions with only mild or absent myocarditis.
      There was a statistically significant correlation between the presence of T.
      cruzi antigens and moderate or severe myocarditis (chi-square = 5.169, p =
      0.023). The results of this in vivo study demonstrate that T. cruzi antigens are
      frequently detected in chronic Chagas' heart disease. In addition, there is an
      association between the intensity of the inflammatory process and the presence of
      T. cruzi antigens. The presence of the T. cruzi antigen and its correlation with
      the severity of myocardial inflammatory process provide strong supportive
      evidence for the role of T. cruzi even in the chronic forms of Chagas' heart
      disease.

PMID- 8579026
TI  - Improved detection of cardiac contusion with cardiac troponin I.
AB  - Detecting cardiac injury in patients with chest trauma is difficult because the
      level of the MB isoenzyme of creatine kinase (MBCK) can be elevated from skeletal
      muscle injury alone. However, the level of cardiac troponin I (cTnl) is not
      elevated by skeletal muscle injury. To determine whether its measurement would
      improve the ability to detect cardiac injury in patients with blunt chest trauma,
      44 patients were studied. Serial echocardiograms and serial blood samples were
      obtained. Six patients had evidence of cardiac injury by echocardiography; all
      had elevations of MBCK and cTnl. One patient had elevations of both MBCK and cTnl
      with only a pericardial effusion. Twenty-six of the 37 patients without contusion
      had elevations of MBCK; none had elevations of cTnl. The ratio of MBCK to total
      creatine kinase improved specificity at the expense of sensitivity. Measurement
      of cTnl accurately detects cardiac injury in patients with blunt chest trauma and
      should facilitate the diagnosis and management of such patients.

PMID- 8579027
TI  - Weight reduction regresses left ventricular mass regardless of blood pressure
      level in obese subjects.
AB  - The effects of weight reduction on left ventricular mass in obese normotensive
      and hypertensive subjects were investigated. Previous studies have shown that
      weight reduction in hypertensive (HT) obese patients is associated with decreased
      left ventricular mass (LVM) and decreased blood pressure (BP). This study was
      performed to examine whether weight reduction would also regress LVM in
      normotensive (NT) obese subjects and to clarify the mechanisms of these effects
      if they occurred. A weight-reduction program consisted of mild exercise and mild
      hypocaloric intake. M-mode echocardiography was performed to estimate the LVM.
      After the 12-week intervention, the mean reductions in body weight (BW) in the NT
      (n = 11) and HT (n = 11) groups were 4.9 kg (p < 0.005) and 4.6 kg (p < 0.0005),
      respectively. Systolic, diastolic, and mean BP were significantly reduced by 13,
      9, and 11 mm Hg, respectively, in the HT group. By contrast, no significant
      changes in systolic, diastolic, or mean BP were observed in the NT group. LVM was
      significantly reduced from 176 +/- 26 gm to 159 +/- 26 gm (p < 0.05) in the HT
      group and from 167 +/- 33 gm to 145 +/- 34 gm (p < 0.02) in the NT group. These
      results suggest that weight reduction in obese subjects by mild exercise and mild
      hypocaloric intake can lead to a reduction in LVM, regardless of whether the
      subjects have normal or high blood pressure.

PMID- 8579028
TI  - Intracardiac echocardiography: in vitro and in vivo validation for right
      ventricular volume and function.
AB  - To determine the feasibility and accuracy of intracardiac ultrasonography (ICUS)
      for the measurement of right ventricular (RV) volumes and function, a 10 MHz ICUS
      catheter was used in an in vitro and in vivo model. In the in vitro study, 16
      sheep hearts were imaged. Sequential cross-sectional images from RV apex to base
      were recorded during a calibrated pullback. Volumes were calculated by applying
      Simpson's algorithm. ICUS-obtained volumes correlated well with actual volumes
      (standard error of estimate [SEE] = 2.3 ml, r = 0.98). For the in vivo study, a
      beating-heart canine model was used (31 hemodynamic stages in six dogs). Actual
      volumes were measured by an intracavitary balloon connected to an external
      column. Sequential cross-sectional images were recorded during the ICUS catheter
      pullback from apex to base of the RV, and volumes calculated by Simpson's
      algorithm. Good correlations were observed between ICUS and actual values for
      diastolic (SEE = 4.1 ml, r = 0.97), systolic (SEE = 3.4 ml, r = 0.96), and
      ejection fraction (SEE = 3.1%, r = 0.87) values. This new technique can
      accurately quantitate RV volumes, can function both in vitro and in vivo, and has
      the potential for increasing applications to questions of clinical and research
      interest.

PMID- 8579029
TI  - Early reduction of neurohumoral factors plays a key role in mediating the
      efficacy of beta-blocker therapy for congestive heart failure.
AB  - This study examined the role played by neurohumoral factors in mediating the
      effects of beta-blocker therapy for congestive heart failure. Fifteen patients
      with congestive heart failure underwent beta-blocker therapy. Plasma
      norepinephrine and alpha-atrial natriuretic peptide concentrations decreased 2
      weeks after initiation of beta-blocker therapy. Decrease in plasma norepinephrine
      level persisted for 6 months. Lymphocyte beta-adrenoceptor density increased 2
      weeks after therapy but was not increased 6 months later. Left ventricular
      ejection fraction was unchanged 2 weeks after therapy, but it increased 6 months
      after introduction of beta-blockers. Plasma norepinephrine level decreased 2
      weeks after the therapy in the responders (increase in ejection fraction > 0.10)
      but not in the nonresponders. Thus early reduction of neurohumoral factor levels
      preceded the late improvement of left ventricular contractile function and may
      therefore be partly responsible for the efficacy of beta-blocker therapy for
      congestive heart failure.

PMID- 8579030
TI  - Changes in plasma endothelin-1 levels reflect clinical response to beta-blockade
      in chronic heart failure.
AB  - Plasma levels of endothelin-1 are elevated in patients with chronic heart
      failure; however, it is unknown whether changes in plasma endothelin-1 levels
      accurately reflect clinical response to therapy in these patients. To determine
      this, we measured plasma endothelin-1 in addition to functional, hemodynamic, and
      other neurohormonal parameters as part of a double-blind, placebo-controlled
      study of the beta-blocker vasodilator carvedilol in patients with moderate to
      severe chronic heart failure. Patients were assigned (2:1 randomization) to
      receive carvedilol (25 mg twice daily, n = 10) or placebo (n = 5) for 14 weeks,
      with evaluations made before and after therapy. Compared to patients receiving
      placebo, patients receiving carvedilol improved significantly as assessed by the
      parameters described. These changes were paralleled by significant falls in
      endothelin-1 with carvedilol (-2.1 + 3.8 pg/ml) in comparison to placebo (2.2 +
      3.9 pg/ml; p < 0.05 for between-group differences). Changes in endothelin-1 after
      treatment in both groups correlated significantly with changes in symptom
      severity, New York Heart Association class, 6-minute walk distance (r = 0.64 to
      0.80; p < 0.05), hemodynamic parameters (ejection fraction, right atrial
      pressure, pulmonary artery diastolic pressure, pulmonary wedge pressure, right
      atrial pressure, and stroke volume index; r = 0.54 to 0.86; p < 0.05), and
      neurohormonal parameters (serum aldosterone and plasma norepinephrine (r = 0.74
      to 0.76; p < 0.05). By stepwise regression analysis, change in endothelin-1 was
      an independent, noninvasive predictor of functional and hemodynamic responses to
      therapy in these patients. These findings suggest that endothelin-1 accurately
      reflects functional, hemodynamic, and neurohormonal responses to beta-blocker
      therapy in patients with congestive heart failure. Measurement of endothelin-1
      may therefore be a useful, noninvasive approach to the evaluation of clinical
      response to drug therapy in these patients.

PMID- 8579031
TI  - Influence of captopril on nitroglycerin-mediated vasodilation and development of
      nitrate tolerance in arterial and venous circulation.
AB  - We investigated whether captopril is able to potentiate vasodilation and prevent
      tolerance to a 48-hour infusion of nitroglycerin (NTG). Twenty-six patients were
      randomly assigned to a 7-day regimen of captopril (50 mg/day) or placebo. The
      hemodynamic response to a 0.8 mg sublingual NTG dose was assessed by measuring
      mean arterial pressure (MAP), mean pulmonary artery pressure (PAP), pulmonary
      capillary wedge pressure (PCWP), right atrial pressure (RAP), and cardiac output
      (CO), and calculating systemic (SVR) and pulmonary vascular resistances (PVR).
      The parameters were obtained serially at baseline and 1 to 10 minutes after the
      sublingual NTG application (day 1). Then intravenous NTG was started and
      maintained for 48 hours (1.5 micrograms/kg/min), and the hemodynamic study was
      repeated (day 3). There was no difference between the captopril and the placebo
      groups at day 1 (baseline values and response to sublingual NTG). After the 48
      hour infusion, there was a complete loss of the NTG effects in the placebo group
      (day 1 vs day 3: PAP, 20 +/- 5 mm Hg vs 21 +/- 8 mm Hg; MAP, 86 +/- 11 mm Hg vs
      90 +/- 9 mm Hg; SVR, 1295 +/- 330 mm Hg vs 1380 +/- 465 dyne.sec.cm-5) whereas
      there was still evidence of a persistent vasodilation in the captopril group (day
      1 vs day 3: PAP, 19 +/- 4 mm Hg vs 13 +/- 4 mm Hg; MAP, 84 +/- 9 mm Hg vs 74 +/-
      10 mm Hg; SVR, 1265 +/- 280 mm Hg vs 1140 +/- 425 dyne.sec.cm-5). The response to
      sublingual NTG on day 3 was markedly attenuated in the placebo group only. We
      conclude that captopril does not increase the vasodilatory response to
      nitroglycerin but is able to prevent developing nitrate tolerance in arterial and
      venous circulation.

PMID- 8579032
TI  - Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction
      (SOLVD). SOLVD Investigators.
AB  - In the Studies of Left Ventricular Dysfunction (LVD), enalapril or placebo was
      administered in a double-blind fashion to 6797 participants with ejection
      fraction < or = 0.35. During 40 months' average follow-up, 28.1% of participants
      randomized to enalapril reported side effects compared with 16.0% in the placebo
      group (p < 0.0001). Enalapril use was associated with a higher rate of symptoms
      related to hypotension (14.8% vs 7.1%, p < 0.0001), azotemia (3.8% vs 1.6%, p <
      0.0001), cough (5.0% vs 2.0%, p < 0.0001), fatigue (5.8% vs 3.5%, p < 0.0001),
      hyperkalemia (1.2% vs 0.4%, p = 0.0002), and angioedema (0.4% vs 0.1%, p < 0.05).
      Side effects resulted in discontinuation of blinded therapy in 15.2% of the
      enalapril group compared with 8.6% in the placebo group (p < 0.0001). Thus
      enalapril is well tolerated by patients with LVD; however, hypotension, azotemia,
      cough, fatigue, and other side effects result in discontinuation of therapy in a
      significant minority of patients.

PMID- 8579033
TI  - Occlusion of large atrial septal defects with a centering buttoned device: early
      clinical experience.
AB  - A feasibility clinical study was conducted for the transcatheter occlusion of
      large ostium secundum atrial septal defects with the centering buttoned device.
      The centering buttoned device is a modification of the regular buttoned device in
      which a centering counter-occluder is sutured at the central 40% portion of the
      occluder. During centering it is stretched, forming a parachute-shaped structure
      and pulling the occluder over the center of the defect. During buttoning, the
      counter-occluder forms a double figure eight, opposing the right atrial side of
      the atrial septum. Occlusion was performed in 12 patients aged 6 to 56 years. All
      had been rejected for transcatheter occlusion by the regular buttoned device,
      because of either their defect size or the lack of adequate septal rim. The
      defect size varied between 23 and 31 mm, and the device size varied between 45
      and 60 mm. Nine had immediate effective occlusions of their defects and three
      residual shunts. One patient with unbuttoning had hemolysis at 2 weeks and
      underwent surgery. Early results of the transcatheter occlusion of large atrial
      septal defects are promising, and larger clinical trials are justified.

PMID- 8579034
TI  - Transthoracic echocardiography for right ventricular function late after the
      Mustard operation.
AB  - The aim of the study was to assess echocardiographic measurements of right
      ventricular function in 24 patients aged 10.7 to 28.9 years (mean 18.9 years)
      receiving the Mustard baffle repair for transposition of the great arteries.
      Right ventricular ejection fraction (RVEF) from single-plane areas and area
      length volumes, pulsed Doppler mean aortic acceleration, and tricuspid annular
      plane systolic excursion were correlated with first-pass radionuclide RVEF. The
      mean radionuclide RVEF was 39%, the mean echocardiographic apical four-chamber
      RVEF was 41%, and the mean short-axis RVEF was 37%. Echocardiographic apical four
      chamber right ventricular end-diastolic volumes were 102 +/- 24 ml/m2, and RVEF
      interobserver and intraobserver correlation coefficients were 0.73 and 0.81,
      respectively. Radionuclide and echocardiographic RVEF correlation coefficients
      were short axis, 0.40; apical four-chamber, 0.24; average four-chamber and short
      axis, 0.38; mean aortic acceleration, 0.26; and tricuspid annular plane systolic
      excursion, 0.06. The range of echocardiographic right ventricular volumes for
      young adults receiving the Mustard repair is established allowing serial
      observation of dilatation. However, simple and reliable echocardiographic
      prediction of RVEF remains elusive in this age group.

PMID- 8579035
TI  - Transcatheter closure of the patent ductus arteriosus: comparison between the
      Rashkind occluder device and the anterograde Gianturco coils technique.
AB  - Thirty-five patients (mean age 43.7 months, mean weight 13 kg) underwent
      anterograde patent ductus arteriosus (PDA) occlusion with Gianturco coils (coil
      group). These patients were compared with 35 age- and weight-matched patients who
      underwent closure of their PDA with the Rashkind umbrella device (device group).
      The mean PDA diameter at its narrowest point was 2.8 mm in the coil group and 2.7
      mm in the device group. There was immediate closure angiographically in 20 (57%)
      of 35 in the coil group compared with 9 (26%) of 35 for the device group. Color
      flow mapping before discharge revealed complete closure in 30 (86%) of 35 in the
      coil group compared with 18 (51%) of 35 in the device group (chi square = 9.5455,
      p < 0.005). Mean fluoroscopy time was 18.5 minutes (median 13.5 minutes) and 14.7
      minutes (median 13 minutes) for the coil and device, respectively. Four coils and
      one device embolized down the pulmonary artery; all were successfully retrieved
      in the catheterization lab. Coil closure of the small to moderate PDA is safe and
      effective. It is more effective in achieving immediate closure than the Rashkind
      device. More clinical trials with the coil technique are warranted to establish
      the long-term results of this technique.

PMID- 8579036
TI  - Unstable coronary ischemic syndromes caused by coronary-subclavian steal.

PMID- 8579037
TI  - Atherosclerosis: risk factors and the vascular endothelium.
AB  - The endothelium can respond to a local environment by releasing a variety of
      substances that regulate the level of vascular tone. One of the most important of
      these vasoregulatory substances is EDRF. The function of the endothelium is
      altered in a variety of pathologic and physiologic conditions. This review
      focused on the role of risk factors for atherosclerosis as it relates to EDRF.
      Atherosclerotic blood vessels respond abnormally on exposure to stimuli that
      release EDRF. It is now also apparent that this abnormal vascular response may
      precede the development of significant atherosclerosis and that normalization of
      the EDRF response with treatment is possible. Thus abnormal endothelium-dependent
      relaxation has been demonstrated in hypercholesterolemic patients with little or
      no evidence of coronary angiographic disease and in patients with hypertension
      before the development of atherosclerosis. The interaction between risk factors
      and the function of the vascular endothelium with development of atherosclerosis
      may become a useful focus for therapies that benefit patient outcomes.

PMID- 8579038
TI  - Epidemiology of hypertension in African American women.
AB  - To describe the epidemiology of hypertension in U.S. African American women and
      to highlight priority areas for future research, data from the nationwide surveys
      of the U.S. National Center for Health Statistics, from selected multicenter
      studies of the U.S. National Heart, Lung, and Blood Institute, as well as from
      selected other population-based studies, were reviewed. In 1988 through 1991, an
      estimated 3 million African American women aged 18 and older had hypertension.
      Compared with that in U.S. whites, hypertension in black women is characterized
      by higher incidence, earlier onset, longer duration, higher prevalence, and
      higher rates of hypertension-related mortality and morbidity. Risk factors for
      hypertension incidence in black women include obesity and weight gain. The
      effectiveness of drug therapy of hypertension has been established in black
      women, and important gains in rates of treatment and control have been
      accomplished. Nevertheless, rates of hypertension-related mortality for black
      women remain among the highest in the industrialized nations. Further research on
      causes and prevention of hypertension in black women is needed. Goals related to
      prevention and control of hypertension in African Americans for the year 2000
      have been established and must be vigorously pursued.

PMID- 8579039
TI  - Transcatheter embolization in treatment of congenital coronary artery aneurysm.

PMID- 8579040
TI  - Left ventricular and aortic valve thrombosis caused by polycythemia rubra vera
      successfully treated with streptokinase.

PMID- 8579041
TI  - Primary right atrial fibrosarcoma diagnosed by endocardial biopsy.

PMID- 8579042
TI  - Transvenous biopsy of a right atrial tumor under transesophageal
      echocardiographic guidance.

PMID- 8579043
TI  - Persistent atrial standstill documented over a 22-year period.

PMID- 8579044
TI  - Dilated cardiomyopathy associated with chronic consumption of phendimetrazine.

PMID- 8579045
TI  - Verapamil and circadian variation of sudden cardiac death.

PMID- 8579046
TI  - Traumatic occlusion of the right coronary artery resulting in cardiogenic shock
      successfully treated with primary angioplasty.

PMID- 8579047
TI  - Coronary artery obstruction caused by perivalvular abscess in aortic valve
      endocarditis.

PMID- 8579048
TI  - Lesions of mediastinal paraganglia in chronic chagasic cardiomyopathy: cause of
      sudden death?

PMID- 8579049
TI  - Cytomegalovirus surveillance and prevention in allogeneic bone marrow
      transplantation: examination of a preemptive plan of ganciclovir therapy.
AB  - Forty-two cytomegalovirus (CMV)-seropositive allogeneic marrow transplant
      patients or recipients of CMV-seropositive marrow allografts were entered into a
      surveillance program to detect and treat CMV infection during the first 120 days
      posttransplant. CMV infection was detected at a mean time of day 50 in 21/37
      (58%) patients who had surveillance cultures. Twelve of 42 (28%) received
      preemptive ganciclovir treatment for virus isolated from blood (9 patients) or
      from bronchoalveolar lavage fluid (3 patients), and all had no CMV-associated
      sequelae. CMV disease was diagnosed in 5 patients (4 with pneumonia), 1 with
      gastroenteritis) who did not have positive cultures until the onset of their
      disease. CMV-related mortality was 4/42 (10%). Patients who earlier manifested
      lung injury or diffuse alveolar hemorrhage (DAH) were significantly predisposed
      to subsequent CMV pneumonia (P = 0.0013, Fisher's exact test) at a median onset
      of day 42. Restricted prophylactic use of ganciclovir in such patients may be
      indicated. Fifty percent of all patients never required ganciclovir during the
      surveillance period. When compared to a universal prophylaxis program of
      ganciclovir for the prevention of CMV disease, the use of ganciclovir in a
      preemptive strategy could avoid unnecessary therapy for a substantial number of
      patients and earn significant cost-savings.

PMID- 8579050
TI  - Danazol relieves refractory pruritus associated with myeloproliferative disorders
      and other diseases.
AB  - Severe pruritus is frequently associated with myeloproliferative and other
      systemic illnesses, and often fails to respond to conventional measures. We used
      danazol (Danocrine), a synthetic attenuated androgen, in the treatment of severe
      pruritus refractory to conventional therapy. Eight patients had
      myeloproliferative disorders (MPD), seven had autoimmune disorders, and seven had
      skin diseases. Danazol at 400-800 mg/day was administered, and previous
      medications were tapered off. When itching was controlled with danazol alone, the
      dosage was reduced or discontinued, and resumed if itching recurred. Clinical
      responses were graded, and side effects were monitored. Overall, in 12 of 22
      patients refractory to other measures, itching was controlled with danazol alone.
      In 10 patients itching returned when danazol was discontinued or dosage was
      continued for up to 5 years in responders. No serious side effects were observed.
      Our experience indicates that danazol is a good alternative for patients with
      severe pruritus associated with myeloproliferative and other systemic disorders.

PMID- 8579051
TI  - Pilot study of 5-azacytidine (5-AZA) and carboplatin (CBDCA) in patients with
      relapsed/refractory leukemia.
AB  - 5-azacytidine (5-AZA) and carboplatin (CBDCA) are two agents which have
      demonstrated antileukemic activity in a number of phase I-II trials. Their
      mechanisms of action and pharmacology related to cell resistance suggested
      suitability for combination therapy. The aim of this pilot was to evaluate the
      effects of this combination in the treatment of patients with relapsed/refractory
      acute leukemia. A total of 21 patients was enrolled. 5-azacytidine, at doses
      ranging from 50-150 mg/m2/day, was administered as a 2-hr infusion for 5
      consecutive days. On day 3, patients began a 5-day course of CBDCA given as a 24
      hr continuous intravenous infusion of 250 mg/m2/day. There were no complete
      remissions with this regimen. Although there were three partial responses, these
      were generally of short duration. Nonhematologic toxicities were mild. No
      correlation was seen between response and serum platinum levels. These results
      demonstrate that the 5-AZA/CBDCA combination is ineffective therapy for heavily
      pretreated patients with acute leukemia.

PMID- 8579052
TI  - Molecular basis of erythroenzymopathies associated with hereditary hemolytic
      anemia: tabulation of mutant enzymes.
AB  - Molecular abnormalities of erythroenzymopathies associated with hereditary
      hemolytic anemia have been determined by means of molecular biology. Pyruvate
      kinase (PK) deficiency is the most common and well-characterized enzyme
      deficiency in the glycolytic pathway, and it causes hereditary hemolytic anemia.
      To date, 47 gene mutations have been identified. We identified one base deletion,
      one splicing mutation, and six distinct missense mutations in 12 unrelated
      families with a homozygous PK deficiency. Mutations located near the substrate or
      fructose-1,6- diphosphate binding site may change the conformation of the active
      site, resulting in a drastic loss of activity and severe clinical symptoms.
      Glucose-6-phosphate dehydrogenase (G6PD)deficiency is the most common metabolic
      disorder, and it is associated with chronic hemolytic anemia and/or drug- or
      infection-induced acute hemolytic attack. An estimated 400 million people are
      affected worldwide. The mutations responsible for about 78 variants have been
      determined. Some have polymorphic frequencies in different populations. Most
      variants are produced by one or two nucleotide substitutions. Molecular studies
      have disclosed that most of the class 1 G6PD variants associated with chronic
      hemolysis have the mutations surrounding either the substrate or the NADP binding
      site. Among rare enzymopathies, missense mutations have been determined in
      deficiencies of glucosephosphate isomerase, (TPI), phosphoglycerate kinase, and
      adenylate kinase. Compound heterozygosity with missense mutation and base
      deletion has been determined in deficiencies of hexokinase and
      diphosphoglyceromutase. Compound heterozygosity with missense and nonsense
      mutations has been identified in TPI deficiency. One base junction mutations
      resulting in abnormally spliced PFK-M mRNA have been identified in homozygous PFK
      deficiency. An exception is hemolytic anemia due to increased adenosine deaminase
      activity. The basic abnormality appears to result from the overproduction of a
      structurally normal enzyme.

PMID- 8579053
TI  - Priapism following splenectomy in an unstable hemoglobin: hemoglobin Olmsted beta
      141 (H19) Leu-->Arg.
AB  - We report a case of severe priapism occurring in a patient with an unstable
      hemoglobin, Hb Olmsted (beta 141 Leu-->Arg) This is a rare hemoglobin variant,
      which until now has been reported only once. The clinical course of the 12-year
      old boy was characterized by severe hemolytic anemia leading to splenectomy and
      cholecystectomy at the of 3.5 years. The priapism occurred 8 years after
      splenectomy, during a hemolytic febrile episode and required aspiration of the
      corpora cavernosa. This report raises the question of the benefit of splenectomy
      in patients suffering from a chronic hemolytic anemia such as that due to an
      unstable hemoglobin. This treatment lowers the frequency and the severity of
      acute hemolytic attacks, but several cases of vascular complications have been
      reported after splenectomy.

PMID- 8579055
TI  - Polyclonal B cell chronic lymphoproliferative disease with hairy cell morphology:
      a case report and clonal studies.
AB  - We describe a patient who has a chronic polyclonal B lymphocyte proliferation
      with a hairy-cell appearance. A 48-year-old Japanese woman with marked
      splenomegaly, systemic lymphadenopathy, and leukocytosis was referred to out
      hospital. Laboratory examination revealed marked polyclonal IgG
      hypergammaglobulinemia. Morphologic examination of the patient's peripheral
      blood, including May-Giemsa staining and scanning electron microscopy, showed a
      monotonous proliferation of hairy-appearing mature lymphocytes. An
      immunophenotypic study revealed an expansion of cells with mature B cell antigens
      positive for CD11c; however, light-chain restriction was not seen. The lack of
      both immuno-globulin heavy-chain and T cell receptor gene rearrangements by
      Southern blot analysis indicated the polyclonal nature of the proliferating B
      cells. This was confirmed further by a clonal analysis of the patient's
      lymphocytes using an X-chromosome-linked restriction fragment polymorphism within
      the X-linked phosphoglycerate kinase (PGK) gene. Since chronic B cell
      lymphoproliferation with a hairy cell appearance has not been described
      previously, this case might be extremely rare, and has important implication for
      the pathogenesis of mature B cell lymphoproliferative diseases, including hairy
      cell leukemia.

PMID- 8579054
TI  - Acute myeloid leukemia evolving from essential thrombocythemia in two patients
      treated with hydroxyurea.
AB  - Essential thrombocythemia (ET) is an uncommon myeloproliferative disorder, which
      is thought to develop from a multipotent stem cell. Like other myeloproliferative
      diseases, ET is associated with an increased risk of development of acute
      leukemia (AL). However, the large majority of cases of leukemic transformation in
      ET are thought to be related to prior therapy, usually radioactive phosphorous or
      alkylating chemotherapy, and the development of AL in ET is extremely rare in the
      untreated patient. In this report, two cases of ET which evolved into AL without
      prior exposure to radiation or alkylating agents, and which were treated with
      long-term hydroxyurea therapy, are described. The first case had cytogenetic
      changes in the bone marrow suggestive of therapy-associated leukemia, and the
      second developed myelodysplastic syndrome on therapy which was likely
      chemotherapy-induced and led to acute leukemia. Prolonged used of hydroxyurea in
      patients with ET may lead to therapy-associated acute leukemia.

PMID- 8579056
TI  - Acute lymphoblastic leukemia with myeloperoxidase activity.
AB  - The French-American-British (FAB) classification of acute leukemias is based on
      the light microscopic detection of myeloperoxidase (MPO) activity in blast cells.
      Cells with MPO activity in > 3% of cells are classified as acute myeloid leukemia
      (AML) and usually express myeloid cell surface antigens. We describe a case of
      acute leukemia in which the blast cells have lymphoid morphology, ultrastructure,
      immunophenotype, and molecular rearrangements, but express significant amounts of
      MPO. We discuss the incidence, features, and outcome of MPO-positive acute
      lymphoblastic leukemia (ALL).

PMID- 8579057
TI  - Severe thrombocytopenia in patients treated with suramin: evidence for an immune
      mechanism in one.
AB  - Although suramin has long been used to treat human trypanosomiasis, recent
      clinical trials have tested its efficacy against the acquired immunodeficiency
      syndrome (AIDS) and various malignancies. Thromobocytopenia was observed in early
      trials with suramin in AIDS, but has been uncommon in patients treated for solid
      tumors. Here we describe 5 patients out of a total of 67 (7%) who developed
      severe thrombocytopenia while receiving suramin as part of a phase II clinical
      trial for metastatic prostate carcinoma refractory to hormonal therapy. IgG
      purified from one patient's plasma caused suramin-dependent platelet aggregation.
      There was also evidence of crossreactivity between suramin and heparin in this
      system. An immune mechanism, however, could not be documented in the other cases,
      suggesting that multiple mechanisms may be responsible for severe
      thrombocytopenia in this patient population.

PMID- 8579059
TI  - Allogeneic bone marrow transplantation in a patient with hypereosinophilic
      syndrome.
AB  - We describe a 32-year-old man with idiopathic hypereosinophilic syndrome (HES)
      who presented with pulmonary dysfunction, thrombocytopenia, lymphadenopathy, and
      hepatosplenomegaly. The patient developed progressive disease on prednisone and
      hydroxyurea therapy, and he underwent a successful allogeneic bone marrow
      transplantation (BMT). The patient is asymptomatic with no evidence of
      eosinophilia 30 months after transplantation. There is currently no cure for
      patients with HES, and BMT should be considered in selected patients.

PMID- 8579058
TI  - 1-Desamino-8-arginine-vasopressin corrects the hemostatic defects in type 2B von
      Willebrand's disease.
AB  - DDAVP is effective treatment in most types of von Willebrand's disease; however,
      in type 2B von Willebrand's disease the use of DDAVP has been contraindicated due
      to DDAVP-induced thrombocytopenia. Several reports have confirmed the
      thrombocytopenic effects of DDAVP and the presence of circulating platelet
      aggregates in type 2B von Willebrand's disease. We have infused three type 2B
      patients with DDAVP. The three patients had different mutations of their vWf. All
      three patients had a missense mutation which resulted in a single amino acid
      substitution in the disulfide loop of the A1 domain. Administration of 20
      micrograms of DDAVP resulted in significant elevations of factor VIII, vWf
      antigen, and ristocetin cofactor levels. In contrast to other studies, DDAVP did
      not induce or enhance thrombocytopenia in these three patients. When blood was
      obtained by fingerstick and diluted into sodium oxalate (Unopette) or EDTA
      (Microvette), the platelet counts did not change over 4 hr. In contrast, blood
      collected directly into evacuated tubes containing sodium citrate, lithium
      heparin, or EDTA consistently demonstrated varying degrees of thrombocytopenia
      and platelet clumping. We also observed a shortening of the pre-infusion bleeding
      time over the 4 hr period. All three patients have been studied twice and each
      has shown consistent results. DDAVP appears to be a useful form of treatment in
      type 2B vWd.

PMID- 8579060
TI  - Normalization of serum lactic dehydrogenase in beta-thalassemia patients
      following bone marrow transplantation.
AB  - Serum lactic dehydrogenase (LDH) levels are mildly elevated in beta-thalassemia
      major due to ineffective erythropoiesis. We reviewed the charts of 15 consecutive
      thalassemic children who underwent allogeneic, T-cell-depleted bone marrow
      transplantation (BMT) in our department during the last 3 years. Eleven patients
      had successful engraftment and are alive and well without evidence of disease,
      according to physical examinations, blood counts, and polymerase chain reaction
      (PCR) tests, with a median follow-up of 2 years. Two patients died due to
      transplantation-related complications, and two rejected the graft and received
      their backup autologous marrow. The LDH levels in the transplanted patients
      gradually decreased from an average of 952 +/- 155 IU/L 10 days pre-transplant (N
      = 300-620) to 426 +/- 56 IU/L at the day of transplantation, and stayed at
      approximately the same level post-transplant (489 +/- 55 IU/L). By contrast, the
      LDH levels reverted to the pre-transplant value in those patients who rejected
      their marrow. The significance of this clinical observation for the
      pathophysiologic mechanism of intramedullary hemolysis and ineffective
      erythropoiesis in beta-thalassemia major is discussed.

PMID- 8579061
TI  - Safety and efficacy of purified factor IX concentrate and antifibrinolytic agents
      for dental extractions in hemophilia B.
AB  - This study evaluated the safety and efficacy of combined treatment with epsilon
      aminocaproic acid or tranexamic acid and monoclonal antibody purified factor IX
      (MAb factor IX) for prophylaxis against bleeding in eight hemophilia B patients
      undergoing nine dental extraction procedures. All patients achieved excellent
      hemostasis without clinical evidence of thrombosis. There were no significant
      changes in hemoglobin or hematocrit or in markers of hemostatic system activation
      (prothrombin fragment F1+2, fibrinopeptide A, and fragment B beta 15-42) after
      surgery. Thus, a highly purified factor IX concentrate and antifibrinolytic
      therapy can be effectively and safely combined in hemophilia B patients
      undergoing dental extractions.

PMID- 8579062
TI  - AIDS-related pure red cell aplasia.

PMID- 8579063
TI  - Familial polycythemia vera in father and daughter.

PMID- 8579064
TI  - Intravenous immune globulins and hypothermia.

PMID- 8579065
TI  - Multiple spontaneous vascular infarcts in sickle-cell trait: a case report.

PMID- 8579066
TI  - High-dose biscoclaurine alkaloids together with prednisolone raise platelet
      counts in chronic idiopathic thrombocytopenic purpura.

PMID- 8579067
TI  - Acute hemolytic anemia precipitated by myocardial infarction and pericardial
      tamponade in G6PD deficiency.

PMID- 8579068
TI  - Burkitt's lymphoma in a patient with recurrent pericarditis.

PMID- 8579069
TI  - Chronobiological circadian aspects of serum lactate dehydrogenase and serum
      thymidine kinase in monitoring multiple myeloma.

PMID- 8579070
TI  - Atypical follicular hyperplasia with clonal rearrangement for immunoglobulin and
      T-cell receptor genes: biclonal proliferation of B cell and T cell.

PMID- 8579071
TI  - Pseudohyperphosphatemia in multiple myeloma.

PMID- 8579072
TI  - Subclinical auditory and visual involvement during oral deferiprone therapy.

PMID- 8579073
TI  - In vitro factor VIII recovery during the delivery of ultrapure factor VIII
      concentrate by continuous infusion.
AB  - Factor VIII (FVIII) replacement by continuous infusion has been advocated as a
      cost-effective method for maintaining stable plasma levels of FVIII in the
      hemophilia A patients during surgery or life-threatening hemorrhage. Continuous
      delivery of monoclonal or recombinant FVIII concentrates to our pediatric
      patients using a traditional delivery system (dilution in normal saline of 2-10
      U/ml infused at a rate of 20 ml/hr) has frequently yielded higher than expected
      factor usage to achieve desired levels and unexpected variability in plasma
      levels under presumed steady-state conditions. To determine if diminished in
      vitro FVIII recovery was responsible for these observations, a study of four
      ultrapure concentrates during 8 hr of in vitro continuous delivery was performed
      using four delivery systems. When reconstituted concentrate was added to normal
      saline in polyvinylchloride bags at a concentration of 10 U/ml (method IA),
      monoclonal products showed a stable recovery of 84-109% of time 0 levels.
      Recombinant product recovery dropped to 57-76% of time 0 levels before
      reapproximating the time 0 level at 2 hr. The addition of 10 mg/ml human albumin
      to the bags (method IB) did not improve recoveries. When reconstituted
      concentrate was delivered undiluted (method IIA), the early drop in recombinant
      recovery was eliminated; stable recovery of 78-117% of time 0 level was achieved
      with all products. In using method IA, a large discrepancy was seen between the
      actual time 0 recoveries and those expected based on vial assays, most striking
      for recombinant products (49-57% of expected. Method IIA allowed 75-90% recovery;
      addition of 20 mg/ml albumin of reconstituted but undiluted concentrate (method
      IIB) maximized recovery at 85-98% of expected.

PMID- 8579074
TI  - The future role of subspecialists in departments of internal medicine.

PMID- 8579075
TI  - Fever, rash, testicular swelling, and eosinophilia in an 86-year-old man.

PMID- 8579076
TI  - Short course dexamethasone for thrombocytopenia in AIDS.

PMID- 8579077
TI  - Pharmacokinetics of the newer antidepressants.

PMID- 8579078
TI  - Emerging and reemerging infections.

PMID- 8579079
TI  - Applied physiology for the frustrated phlebotomist.

PMID- 8579080
TI  - Niacin: a therapeutic dilemma.

PMID- 8579081
TI  - The use of growth factors with antibiotics in the setting of neutropenic fever.

PMID- 8579083
TI  - Contrasting methicillin-resistant Staphylococcus aureus colonization in Veterans
      Affairs and community nursing homes.
AB  - PURPOSE: To compare the prevalence of methicillin-resistant Staphylococcus aureus
      (MRSA) nares colonization, the patterns of MRSA acquisition, and the risk for
      subsequent MRSA infection between a hospital-based, Department of Veterans
      Affairs (VA) nursing home care unit (NHCU) and community-based nursing homes.
      PATIENTS AND METHODS: In this prospective study, 148 residents of three community
      nursing homes and 55 residents of a VA NHCU had their anterior nares swabbed;
      repeat cultures were obtained from hospitalized patients and/or individuals
      colonized with MRSA. Subjects were followed up prospectively for 1 year to note
      hospitalizations and the development of MRSA infections. RESULTS: The prevalence
      of MRSA colonization was significantly higher in the VA NHCU than in the
      community nursing homes (mean +/- SD 30.3% +/- 11% versus 9.9% +/- 4%). The rate
      of MRSA nares colonization was similar in the two settings. Acquisition of MRSA
      took place in both the long-term care facilities and hospitals, with 23.8% of
      incident cases occurring during a hospitalization. Only 3 of the 27 individuals
      colonized at baseline developed an MRSA infection. A trend toward an increased
      rate of infection was seen in colonized individuals residing in the community
      nursing homes versus those in the VA NHCU (relative risk 4.67; 95% Cl 0.55 to
      39.9). Forty-seven percent of the 55 subjects hospitalized were colonized at some
      point during the study. In contrast to residents of the VA NHCU, MRSA
      colonization in the community facilities was a marker for high mortality.
      CONCLUSIONS: Outcomes from colonization may be different in the VA NHCU
      population and the community nursing home population.

PMID- 8579082
TI  - Randomized comparison between antibiotics alone and antibiotics plus granulocyte
      macrophage colony-stimulating factor (Escherichia coli-derived in cancer patients
      with fever and neutropenia.
AB  - PURPOSE: A prospective, randomized study was conducted to determine if
      recombinant human granulocyte-macrophage colony-stimulating factor (rh-GMCSF)
      (Escherichia coli-derived) could improve response rates to antibiotic therapy and
      shorten the duration of neutropenia in cancer patients. PATIENTS AND METHODS: A
      total of 107 febrile neutropenic cancer patients were randomly assigned to
      empiric therapy with ticarcillin-clavulanate (4 g ticarcillin + 0.1 g clavulanate
      i.v. every 4 hours) plus netilmicin (2 mg/kg i.v. every 8 hours) with or without
      rh-GMCSF (3 micrograms/kg per day i.v.). Clinical improvement, duration of
      neutropenia, and toxicity were monitored. RESULTS: Addition of rh-GMCSF to the
      antibiotics significantly improved the response rate (96% versus 82%, P = 0.03),
      but not the survival rate (93% versus 93%), in the evaluable patients. This
      difference in response rate was not significant when considering all patients in
      an intent-to-treat analysis. The number of patients who recovered from severe
      neutropenia ( < 100 cells/microliter) during the period of observation in the
      study was significantly greater among patients receiving the colony-stimulating
      factor, although the median duration of neutropenia was not affected.
      Superinfections and subsequent infections were not significantly different among
      the two treatment regimens. Side effects were more common among patients treated
      with the colony-stimulating factor. CONCLUSIONS: Our data do not support the
      routine administration of rh-GMCSF with antibiotics for patients with fever and
      neutropenia. Further studies should be conducted to identify those patients most
      likely to benefit from rh-GMCSF therapy, such as patients with persistent
      profound neutropenia and refractory infections.

PMID- 8579084
TI  - Clinical and molecular epidemiology of sporadic and clustered cases of nosocomial
      Clostridium difficile diarrhea.
AB  - PURPOSE: A prospective clinical and molecular epidemiologic study was conducted
      to define the frequency of nosocomial Clostridium difficile patient-to-patient
      transmission in an urban tertiary referral hospital. PATIENTS AND METHODS: Over a
      6-month period, environmental cultures for C difficile were obtained from
      patients with new positive stool cytotoxin assay (index cases); stool samples
      were obtained from selected patient contacts (the roommate, occupants of adjacent
      rooms, and the patient occupying the index room after discharge of the index
      case); and hand cultures were obtained from personnel contacts. C difficile
      isolates were analyzed by pulse-field gel electrophoresis (PFGE) or, for isolates
      that were nontypeable by PFGE, by restriction enzyme analysis. RESULTS: During
      the study period, we identified 98 index cases of C difficile toxin-associated
      diarrhea, including focal outbreaks on two wards totaling 26 cases within a 2
      month interval. Environmental contamination was detected at > or = 1 sites in 58%
      of rooms and often involved wide dispersed areas. Among 99 prospectively
      identified patient contacts, C difficile was cultured from the stool of 31 (31%),
      including 12 with diarrhea and 19 who were asymptomatic. C difficile was cultured
      from the hands of 10 (14%) of 73 personnel. Molecular analysis resolved 31 typing
      profiles among the index isolates; the most common profile (designated strain D1)
      was represented by 30 isolates. Among the isolates from patient contacts, 5 of 12
      from symptomatic contacts matched the corresponding index isolate, and only 1 of
      19 from asymptomatically colonized contacts matched. Transmission to personnel or
      patient contacts of the strain cultured from the corresponding index case was
      correlated strongly with the intensity of environmental contamination. Strain D1
      was frequently represented among isolates associated with heavy environmental
      contamination, with personnel carriage, and with development of symptomatic
      illness among prospectively identified contacts. CONCLUSIONS: Intense
      environmental contamination and transmission to close personnel and patient
      contacts represented coordinated properties of an individual epidemic strain. For
      most epidemiologically linked contacts, positive cultures for C difficile did not
      result from transmission from the presumed index case.

PMID- 8579085
TI  - Occupational risk of hepatitis C infections among general dentists and oral
      surgeons in North America.
AB  - PURPOSE: To assess the occupational risk of hepatitis C virus (HCV) infection
      among dental personnel. METHODS: Three hundred forty-three oral surgeons and 305
      general dentists were recruited at national meetings of the American Dental
      Association and matched by gender, age, years of practice, and location of
      practice. Each participant completed a detailed questionnaire designated to
      measure occupational risk of blood-borne infections and supplied a sample of
      blood. Antibodies to HCV (anti-HCV) were assessed by second-generation enzyme
      immunoassay and recombinant immunoblot assay. As a marker of occupational
      exposure to blood-borne viruses, hepatitis B virus (HBV) surface antigen and
      antibodies to HBV surface and core antigens were measured by enzyme immunoassay.
      RESULTS: Anti-HCV was found in 2.0% of oral surgeons and 0.7% of general dentists
      (odds ratio [OR] = 3.2, P = 0.133). Anti-HCV was more prevalent (P < 0.01) in
      dental personnel who were older, had more years of practice, and had serologic
      markers of HBV infection. Serologic markers of HBV infection were found in 7.8%
      of general dentists and 21.2% of oral surgeons (OR 3.1, P < 0.001). CONCLUSIONS:
      These data confirm high rates of HBV infection among dental personnel, but
      suggest that the risk of HCV infection is considerably lower.

PMID- 8579086
TI  - Hantavirus pulmonary syndrome in Florida: association with the newly identified
      Black Creek Canal virus.
AB  - Hantavirus pulmonary syndrome (HPS) is a recently recognized viral zoonosis. The
      first recognized cases were caused by a newly described hantavirus. Sin Nombre
      virus (previously known as Muerto Canyon virus), isolated from Peromyscus
      maniculatus (deer mouse). We describe a 33-year-old Floridian man who resided
      outside the ecologic range of P maniculatus but was found to have serologic
      evidence of a hantavirus infection during evaluation of azotemia associated with
      adult respiratory distress syndrome. Small mammal trapping conducted around this
      patient's residence demonstrated the presence of antihantaviral antibodies in 13%
      of Sigmodon hispidus [cotton rat). Serologic testing using antigen derived from
      the Black Creek Canal hantavirus subsequently isolated from this rodent
      established that this patient was acutely infected with this new pathogenic
      American hantavirus. HPS is not confined to the geographical distribution of P
      maniculatus and should be suspected in individuals with febrile respiratory
      syndromes, perhaps associated with azotemia, throughout the continental United
      States.

PMID- 8579087
TI  - Malaria among United States troops in Somalia.
AB  - PURPOSE: United States military personnel deployed to Somalia were at risk for
      malaria, including chloroquine-resistant Plasmodium falciparum malaria. This
      report details laboratory, clinical, preventive, and therapeutic aspects of
      malaria in this cohort. PATIENTS AND METHODS: The study took place in US military
      field hospitals in Somalia, with US troops deployed to Somalia between December
      1992 and May 1993. Centralized clinical care and country-wide disease
      surveillance facilitated standardized laboratory diagnosis, clinical records,
      epidemiologic studies, and assessment of chemoprophylactic efficacy. RESULTS:
      Forty-eight cases of malaria occurred among US troops while in Somalia; 41 of
      these cases were P falciparum. Risk factors associated with malaria included:
      noncompliance with recommended chemoprophylaxis (odds ratio [OR] 2.4); failure to
      use bed nets (OR 2.6); and failure to keep sleeves rolled down (OR 2.2). Some
      patients developed malaria in spite of mefloquine (n = 8) or doxycycline (n = 5)
      levels of compatible with chemoprophylactic compliance. Five mefloquine failures
      had both serum levels > or = 650 ng/mL and metabolite:mefloquine ratios over 2,
      indicating chemoprophylactic failure. All cases were successfully treated,
      including 1 patient who developed cerebral malaria. CONCLUSIONS: P falciparum
      malaria attack rates were substantial in the first several weeks of Operation
      Restore Hope. While most cases occurred because of noncompliance with personal
      protective measures or chemoprophylaxis, both mefloquine and doxycycline
      chemoprophylactic failures occurred. Military or civilian travelers to East
      Africa must be scrupulous in their attention to both chemoprophylaxis and
      personal protection measures.

PMID- 8579088
TI  - An examination of the working case definition of chronic fatigue syndrome.
AB  - PURPOSE: Chronic fatigue syndrome (CFS) currently is defined by a working case
      definition developed under the leadership of the United States Centers for
      Disease Control and Prevention (CDC) based on a consensus among experienced
      clinicians. We analyzed the experience from one large center to examine the
      adequacy of the case definition. PATIENTS AND METHODS: Predefined clinical and
      laboratory data were collected prospectively from 369 patients with debilitating
      fatigue, of whom 281 (76%) met the major criteria of the original CDC case
      definition for CFS: (1) fatigue of at least 6 months' duration, seriously
      interfering with the patient's life; and (2) without evidence of various organic
      or psychiatric illnesses that can produce chronic fatigue. The same clinical data
      were obtained from 311 healthy control subjects and two comparison groups with
      diseases that can present in a similar fashion; relapsing-remitting multiple
      sclerosis (n = 25) and major depression (n = 19). RESULTS: All of the minor
      criteria symptoms from the original CDC case definition distinguished patients
      with debilitating chronic fatigue from healthy control subjects, and many
      distinguished the patients with chronic fatigue from the comparison groups with
      multiple sclerosis and depression: myalgias, postexertional malaise, headaches,
      and a group of infectious-type symptoms (ie, chronic fever and chills, sore
      throat, swollen glands in the neck or underarm areas). In addition, two other
      symptoms not currently part of the case definition discriminated the chronic
      fatigue patients from the control/comparison groups: anorexia and nausea.
      Physical examination criteria only infrequently contributed to the diagnosis.
      Patients meeting the CDC major criteria for CFS also met the minor criteria in
      91% of cases. CONCLUSION: Patients meeting the major criteria of the current CDC
      working case definition of CFS reported symptoms that were clearly
      distinguishable from the experience of healthy control subjects and from disease
      comparison groups with multiple sclerosis and depression. Eliminating three
      symptoms (ie, muscle weakness, arthralgias, and sleep disturbance) and adding two
      others (ie, anorexia and nausea) would appear to strengthen the CDC case
      definition of CFS.

PMID- 8579089
TI  - Is presentation of bacteremia in the elderly the same as in younger patients?
AB  - OBJECTIVE: To compare the presentation of bacteremia in young and elderly
      patients. PATIENTS AND METHODS: Seventy-one elderly (mean age 80.4 years) and 34
      younger inpatients (mean age 45.7 years) with bacteremia were prospectively
      studied. These were compared with a control group of 187 geriatric patients (mean
      age 81.3 years) with clinical signs of bacteremia but in whom blood cultures were
      negative. Bacteremia was defined as one or more positive blood cultures showing a
      pathogenic bacteria in patients with clinical signs of bacteremia. In all 105
      patients with bacteremia, 16 common clinical or biological signs of the disease
      were immediately investigated after blood culture. Patients were classified into
      three groups: elder patients and young patients with bacteremia and elderly
      patients without bacteremia. RESULTS: Only three clinical findings of the 16
      studied were found in at least 70% of the bacteremic elderly patients: fever,
      increased erythrocyte sedimentation rate, and a clinical indication of the source
      of infection. These three signs were found statistically more often in bacteremic
      elderly compared with nonbacteremic elderly patients (P < 0.01). Seven other
      signs (hypothermia, altered mental state, leukopenia, and lymphopenia) had a
      specificity above 80%. On a logistic regression analysis, four variables were
      significantly and independently associated with bacteremia in the elderly: rapid
      onset of infection (defined as a period < or = 48 hours between the earliest
      manifestation of bacteremia and the time of blood blood sample), fever, altered
      general state, and clinical indication of the source of infection. Younger
      infected patients had more chills, sweating, alter general state, altered mental
      state or lymphopenia than did the bacteremic elderly patients. Bacteremic elderly
      patients had statistically few symptoms than the young infected patients (P <
      0.001). CONCLUSIONS: In elderly patients with early stage bacteremia, most of the
      signs or symptoms that are considered typical in the literature appear
      irregularly. None appeared pathognomonic. Elderly patients with bacteremia had
      fewer signs or symptoms than younger infected patients.

PMID- 8579090
TI  - Febrile urinary infection in the institutionalized elderly.
AB  - PURPOSE: Bacteriuria is common among institutionalized elderly populations, but
      the contribution of urinary infection to febrile morbidity is unknown because of
      difficulties in clinical ascertainment. This study was undertaken to febrile
      morbidity using both clinical and serologic criteria. METHODS: Episodes of fever
      in residents of two long-term care institutions were identified prospectively for
      2 years. Serum and urine specimens were obtained initially and at 4 weeks. The
      proportion of episodes attributable to urinary infection was determined by both
      standard clinical criteria proposed for use in these populations and serum
      antibody response to uropathogens. RESULTS: For 372 fewer episodes, 211 met
      clinical criteria for infection: 147 (40%) of the respiratory tract; 26 (7%) of
      the genitourinary tract; 25 (6%) of the gastrointestinal tract; and 13 (3%) of
      skin and soft tissue. Of the remaining 161 fever episodes, 2 (1%) were
      noninfectious and 159 (43%) were of unknown origin. The prevalence of bacteriuria
      for residents with nongenitourinary sources of fever varied from 32% to 75%. An
      antibody response meeting serologic criteria for urinary infection occurred in 26
      (8.3%) of 314 episodes with paired sera obtained; 10 (43%) of 23 identified
      clinically as genitourinary infection, 14 (11%) of 132 unknown, 1 (4%) of 25
      gastrointestinal, and 1 (0.8%) of 122 respiratory. The positive predictive value
      of bacteriuria for febrile urinary infection identified by clinical criteria was
      was 11% (95% confidence interval [CI] 4%, 18%) and identified by serologic
      criteria was 12% (95% CI 7%, 17%). CONCLUSIONS: Urinary infection contributes to
      less than 10% of episodes of clinically significant fever in this high-prevalence
      bacteriuric population. A restrictive clinical definition for genitourinary
      infection has poor sensitivity and specificity compared with serologic criteria
      for identification of fever of urinary source, and bacteriuria has a low
      predictive value for identifying febrile urinary infection.

PMID- 8579091
TI  - Acute meningitis with a negative Gram's stain: clinical and management outcomes
      in 171 episodes.
AB  - PURPOSE: To characterize the diagnostic spectrum and physician management
      decisions of patients presenting to an emergency department with an acute,
      community-acquired illness, cerebrospinal fluid (CSF) white blood cell count >
      5/mm3, and a negative Gram's stain for bacteria. PATIENTS AND METHODS: In this
      retrospective cohort study over a 2-year period, symptoms, examination findings,
      paraclinical data, physician management, and clinical outcomes were assessed for
      each patient. RESULTS: One hundred sixty-eight patients (171 patient episodes)
      were evaluated. Almost half of the cohort presented in nonsummer months (48%);
      20% of concurrent comorbid disease, and 15% had identified immunocompromising
      conditions. The reported examination findings were diverse, with diverse, with
      fever [49%] and neck stiffness [39%] being the most frequent findings. The
      majority were hospitalized (70%), with a median stay of 4 days. Approximately one
      half underwent computed tomography or magnetic resonance imaging (49%), and
      received empiric treatment with antibiotics (52%). A diagnostic cause was
      established in 23%, with the majority being inherently treatable diseases
      (including syphilis, bacteremia, Lyme disease). Variables significantly
      associated with a subsequent proven diagnostic cause included: age > 60 years;
      presence of comorbid disease (especially immunodeficiency); and presentation in
      winter months. CONCLUSIONS: A large proportion of patients presenting with acute
      meningitis and a negative CSF Gram's stain undergo hospitalization, noninvasive
      cranial imaging, and receive empiric antibiotic therapy. Better clinical
      guidelines are needed to identify the diagnostic and management decisions that
      benefit patient outcome.

PMID- 8579092
TI  - Spontaneous infectious discitis in adults.
AB  - PURPOSE: In adults, discitis most frequently follows spinal surgery. We report 16
      adult patients with spontaneously occurring infectious discitis and compare them
      with an additional 52 patients abstracted from the literature. Infecting
      organisms, predisposing factors, imaging modalities, and response to therapy are
      described. PATIENTS AND METHODS: The medical records of adult patients treated
      for infectious discitis of a community hospital during the past 10 years were
      reviewed. Postoperative spine patients and patients with primary osteomyelitis
      were excluded. Sixteen patients were identified with spontaneous primary
      infection of the disc space. The particulars of comorbid conditions, infection
      organisms, site of culture, and response to antibiotic therapy were noted and
      compared to 52 additional cases of spontaneous discitis reported in the
      literature since 1980. RESULTS: A wide variety of infecting organisms was
      identified as causing spontaneous discitis, in contrast to previous reports of
      both postoperative discitis and spontaneous discitis. Nine of 10 patients with
      positive disc cultures had negative blood cultures. Appropriate antibiotics were
      curative in all patients but 1, regardless of the duration of symptoms. Nuclear
      imaging, computed tomography, and magnetic resonance imaging were all useful,
      although the last appears to be the most sensitive and specific imaging modality
      for detecting discitis. CONCLUSIONS: Spontaneous infectious discitis is an
      uncommon cause of low back pain in adults. Nevertheless, it should be considered
      in any patient with acute or subacute pain. Elevated acute-phase reactants with
      appropriate imaging modality suggest the diagnosis. given the wide variety of
      infecting organisms identified, culture of blood and/or disc for the specific
      causative organism is critical to successful treatment outcome.

PMID- 8579093
TI  - The American Journal of Medicine: the next 50 years.

PMID- 8579094
TI  - Infective endocarditis in the elderly in the era of transesophageal
      echocardiography: clinical features and prognosis compared with younger patients.
AB  - PURPOSE: Advanced age is considered to be associated with a more severe prognosis
      in infective endocarditis (IE), which is relevance in view of a change in
      epidemiology of the disease with an increasing proportion of elderly people. We
      wanted to examine whether in the era of improved diagnostic sensitivity for IE by
      transesophageal echocardiography the clinical course in elderly persons would be
      still more severe than in younger patients. PATIENTS: During the period from 1989
      to 1993, 104 patients with 106 episodes of IE were treated at our university
      hospital. Three groups were compared: group A with 28 patients younger than 50
      years, group B with 58 patients aged 50 to 70, and group C with 20 patients older
      than 70. Transesophageal echocardiography was performed in 78% of the patients;
      it was not performed in 22% of the patients with a conclusive transthoracic
      examination. The patients were followed up for an average of 25 months after the
      diagnosis. RESULTS: No significant differences were observed among the age groups
      with respect to the possible source of infection, the frequency of positive blood
      cultures, and the type of infective organisms. Elderly patients more often had
      predisposing valvular conditions (eg, degenerative and calcified lesions and
      prosthetic valves), which decreased the sensitivity of transthoracic
      echocardiography to 45% as compared with 75% in group A. Transesophageal
      echocardiography improved the diagnostic yield by 45% in group C and by 47% in
      group B. Vegetations were smaller in group C and B as compared with group A,
      whereas other echocardiographic characteristics were similar. Fever and
      leukocytosis were less frequent in group C (55% and 25%, respectively) than in
      group A (82% and 61%, respectively). The interval between the onset of symptoms
      and the diagnosis of IE was similar in all groups. Elderly patients underwent
      surgical therapy as frequently (65%) as the other groups. The 1-year survival in
      group C (26%) was comparable with that in group A (22%) and group B (22%). The
      major determinant of survival was the occurrence of embolic complications.
      CONCLUSION: Infective endocarditis in elderly patients caused less severe
      clinical symptoms than in young patients. The early diagnosis in elderly patients
      was facilitated by the high sensitivity of transesophageal echocardiography,
      which enabled the timely initiation of an appropriate medical and surgical
      therapy. This led to a clinical outcome similar to that for younger patients.

PMID- 8579095
TI  - Immunology of viral hepatitis.
AB  - So far, five major forms of viral hepatitis, hepatitis A, B, C, D, and E, have
      been identified. There appears to be at least one other form of enterically
      transmitted and one other parenterally transmitted hepatotropic virus, but
      characterization of these viruses is still preliminary. The five hepatotropic
      viruses have unique structures, yet all the share the property of inducing
      hepatocellular damage, whether through direct cytotoxicity or through induction
      of immune mechanisms that lead to hepatocellular necrosis. Advances in molecular
      biology in the past decade have enabled researchers to understand much about the
      structure, mechanisms of replication, and viral life cycle of each of these
      viruses, and successful vaccines have been developed for hepatitis A and B.
      However, many problems remain unsolved, including which immune system factors are
      important defenses against these viral infections, which components of the immune
      system are necessary for a successful vaccine, and what allows some viruses, such
      as hepatitis B and hepatitis C virus, to become persistent and lead to chronic
      liver disease.

PMID- 8579096
TI  - Leptomeningeal amyloid and variant transthyretins.

PMID- 8579097
TI  - The Golgi apparatus and the pathogenesis of Alzheimer's disease.

PMID- 8579098
TI  - Meningocerebrovascular amyloidosis associated with a novel transthyretin mis
      sense mutation at codon 18 (TTRD 18G)
AB  - We describe a novel transthyretin mutation at codon 18 where Asp is replaced by
      Gly (D18G) in a Hungarian kindred. This mutation is associated with
      meningocerebrovascular amyloidosis, producing dementia, ataxia, and spasticity.
      Fifty different transthyretin mutations are related to amyloid deposition,
      typically producing a peripheral neuropathy or cardiac dysfunction. These
      symptoms are absent in this family. Up to now, amyloid-beta (A beta), cystatin C,
      and prion proteins have been known to be deposited as amyloid in the brain,
      leading to stroke or dementia. With this report we establish that transthyretin
      amyloid deposition can also produce central nervous system dysfunction as the
      major clinical symptom.

PMID- 8579099
TI  - Ezrin expression in stromal cells of capillary hemangioblastoma. An
      immunohistochemical survey of brain tumors.
AB  - Ezrin is a cytoskeleton-associated protein that appears to link actin filaments
      to the plasma membrane. Immunocytochemical studies suggest that ezrin is
      expressed in epithelial cells but not in mesenchymal cells. In addition, ezrin is
      expressed by certain epithelial tumors, such as renal cell adenocarcinomas. Ezrin
      serves as a tyrosine kinase substrate, and is phosphorylated in epidermal growth
      factor-stimulated cells. Ezrin may thus mediate regulatory signals in different
      cell functions. We studied the distribution of ezrin in 104 cases of primary
      tumors of the central nervous system (CNS) by immunocytochemistry. Special
      interest was focused on capillary hemangioblastoma, owing to its resemblance to
      renal cell adenocarcinoma, and on malignant gliomas, owing to their frequent
      epidermal growth factor receptor amplification. The stromal cells of
      hemangioblastomas were found to be strongly positive for ezrin. No expression was
      detected in gliomas and, except for hemangioblastomas, ezrin expression was
      restricted to those few CNS tumors that show epithelial differentiation, ie,
      choroid plexus papillomas, craniopharyngiomas, ependymomas, and cysts. The
      diffuse cytoplasmic expression of ezrin in the stromal cells of capillary
      hemangioblastoma may indicate that stromal cells overexpress ezrin or express
      ezrin with deficient binding properties.

PMID- 8579100
TI  - Adoptive transfer of experimental allergic encephalomyelitis after in vitro
      treatment with recombinant murine interleukin-12. Preferential expansion of
      interferon-gamma-producing cells and increased expression of macrophage
      associated inducible nitric oxide synthase as immunomodulatory mechanisms.
AB  - In an adoptive transfer model of experimental allergic encephalomyelitis,
      stimulation of lymph node cells with proteolipid protein and recombinant murine
      interleukin (rmIL)-12 before cell transfer accelerated the onset and exacerbates
      clinical disease. In vitro stimulation with proteolipid protein in the presence
      of rmIL-12 was associated with an increase in interferon-gamma-producing cells
      and a decrease in IL-4-producing cells, indicating a preferential expansion of
      Th1 effector cells. This was supported by the finding that severe disease with
      rapid onset could be transferred with as few as 10 x 10(6) rmIL-12-stimulated
      lymph node cells. Immunohistochemical analysis confirmed that the accelerated
      onset of disease after in vitro stimulation with rmIL-12 coincided with an acute
      inflammatory response in the central nervous system. At peak disease, both
      control and rmIL-12 treatment groups exhibited extensive cellular infiltration
      with characteristic perivascular cuffing. No notable differences in either the
      cellular composition or cytokine expression within the lesions were seen between
      groups. However, the frequency of macrophages that stained positively for
      inducible nitric oxide synthase was increased in animals challenged with rmIL-12
      treated lymph node cells. The results suggest that, in addition to promoting the
      preferential expansion of interferon-gamma-producing cells by rmIL-12 in vitro,
      secondary in vivo effects leading to macrophage activation and inducible nitric
      oxide synthase expression may contribute to the severe and protracted course of
      central nervous system inflammation in this model.

PMID- 8579101
TI  - Long-term cultivation of adult rat hepatocytes that undergo multiple cell
      divisions and express normal parenchymal phenotypes.
AB  - The present study succeeded in cultivating normal adult rat hepatocytes for at
      least 85 days without losing their replicative potential and differentiation
      capacity. Small pieces of hepatocyte aggregates (clusters) were prepared from the
      primary culture of hepatocytes and used as starting material for the growth
      experiment. Some of the hepatocytes started to proliferate at 3 days when the
      clusters were cultured in Dulbecco's modified Eagle's medium containing 10% fetal
      bovine serum, 10 ng/ml epidermal growth factor, 10 mmol/L nicotinamide, 0.2
      mmol/L L-ascorbic acid 2-phosphate, and 1% dimethylsulfoxide. Clusters continued
      to grow and formed colonies. All the cells covering colonies expressed normal
      hepatocyte-specific proteins. The number of albumin-expressing cells in the most
      replicative colonies increased sixfold during 32 days. Most of the cells were
      mononucleate and small in size and some of them expressed immature hepatocyte
      markers such as alpha-fetoprotein. Electron microscopy of cells in colonies
      revealed the presence of peroxisomes in the cytoplasm and desmosomes, tight
      junctions, and bile canaliculus-like structures between the cells. Depletion of
      one of the additives inhibited the growth of hepatocytes. The culture medium used
      also supported the growth of stellate cells (Ito cells) that had contaminated the
      original preparation in small numbers and seems to cooperatively stimulate a
      proliferative population of hepatocytes.

PMID- 8579102
TI  - In vitro and in vivo stimulation of the murine immune system by AGM-1470, a
      potent angiogenesis inhibitor.
AB  - AGM-1470, a potent angiogenesis inhibitor, is already engaged in phase I clinical
      trials because of its effectiveness to restrain tumor growth and its lack of
      major side effects. Recently, we showed that AGM-1470 stimulates in vitro human B
      lymphocyte proliferation through T lymphocytes. These data prompted us to explore
      the in vivo effects of AGM-1470 on the immune system in a mouse model. In this
      study, we showed that AGM-1470, in synergy with phytohemagglutinin, stimulates
      the proliferation of murine lymphocytes isolated from lymph nodes. This effect
      was similar to the one observed with human lymphocytes. When injected
      subcutaneously or intraperitoneally into mice at pharmacological doses, AGM-1470
      induced a significant increase of axillary and mesenteric lymph nodes,
      respectively. Histological and morphological analyses showed that this phenomenon
      is mostly due to a hyperplasia of the germinal centers. On average, the area of
      the germinal center of lymph nodes from AGM-1470-treated mice were three times
      larger than in lymph nodes from control mice. Interestingly, no effect was
      observed when AGM-1470 was injected subcutaneously into T-deficient nude mice.
      Our data demonstrate that AGM-1470 stimulates B cell proliferation in vivo as
      suggested by the in vitro experiments. This effect should be taken into account
      in the follow-up of patients treated with this molecule and calls for additional
      studies to determine the biological consequences of such a stimulation on the
      host immune system.

PMID- 8579103
TI  - Expression of the macrophage scavenger receptor, a multifunctional lipoprotein
      receptor, in microglia associated with senile plaques in Alzheimer's disease.
AB  - The macrophage scavenger receptor is a multifunctional receptor whose ligands
      include oxidized low density lipoprotein (LDL), as well as several other
      polyanionic macromolecules. Although the capacity of the receptor to bind
      modified LDL has implicated it in the process of atherosclerosis, its
      physiological role remains uncertain. We have examined human brain for expression
      of macrophage scavenger receptor as part of ongoing studies of lipoprotein
      receptors in the central nervous system. The receptor is expressed on microglia,
      but not on astrocytes, neurons, or vessel-associated structures. In Alzheimer
      disease, there is strong expression of the scavenger receptor in association with
      senile plaques.

PMID- 8579104
TI  - Molecular diagnosis of p53 mutations in gastric carcinoma by touch preparation.
AB  - Thirty-one tumor samples from selected cases of gastric carcinoma were analyzed
      for mutations of the p53 tumor suppressor gene. Template DNA was prepared
      according to the touch preparation procedure, which allowed us to isolate
      clusters of neoplastic cells out of a stromal cellular background to be used as a
      template in the amplification of target exons of the p53 locus. In our present
      study, by polymerase chain reaction/single strand conformation polymorphism
      analysis we give evidence of p53 mutations occurring in the DNA-binding core
      domain of the protein (exons 5 through 9), which are clustered in stages III and
      IV of the disease (six mutations out of seventeen samples; 35%). No p53 mutations
      were detected in fourteen gastric cancer samples at I and II stages. Beside the
      use of conventional molecular scanning procedures, our study proposes the
      application of the touch preparation method to increase the detection of genetic
      alterations in human solid tumors.

PMID- 8579105
TI  - In Alzheimer's disease the Golgi apparatus of a population of neurons without
      neurofibrillary tangles is fragmented and atrophic.
AB  - Recent immunocytochemical and morphometric studies in amyotrophic lateral
      sclerosis, Alzheimer's disease (AD), and aging indicate that the neuronal Golgi
      apparatus is a reliable index of activity or degeneration. To further evaluate a
      possible role of the Golgi apparatus in the pathogenesis of AD, we examined by
      double labeling the neuronal Golgi apparatus, neurofibrillary tangles (NFTs), and
      senile plaques (SPs) in the hippocampus of six cases of AD, and in 13 controls
      including three cases of a rare form of dementia lacking distinctive
      histopathological features. The Golgi apparatus was visualized with a polyclonal
      antiserum against MG-160, a membrane sialoglycoprotein of the organelle, and NFTs
      and SPs were visualized with biotinylated basic fibroblast growth factor (bFGF).
      Only a rare SP contained a few small immunostained elements of the Golgi
      apparatus. Neurons with intracellular NFTs, labeled with biotinylated bFGF,
      contained intensely labeled but deformed Golgi apparatus, which was displaced by
      the NFTs and coalesced into larger irregular granules. In contrast, a population
      of neurons without NFTs displayed fragmentation of the Golgi apparatus, ie, the
      organelle appeared in the form of small round, disconnected, and dispersed
      elements instead of the normal perinuclear network of irregular or linear
      profiles which often extended into the proximal segments of dendrites. In
      addition, the fragmented neuronal Golgi apparatus was atrophic as the percentage
      of the cell surface area occupied by the organelle was 4.4 +/- 0.6% SD, whereas
      in neurons with a normal Golgi apparatus the percentage of the cell surface area
      occupied by the organelle was 10.3 +/- 0.3% SD. The results of this study suggest
      that in AD the Golgi apparatus of a population of neurons without NFTs is
      involved in the pathogenesis of the disease. Considering the role of the Golgi
      apparatus in the processing of polypeptides destined for fast axoplasmic
      transports, the fragmentation of the organelle may be associated with functional
      and structural impairments of axons and presynaptic terminals.

PMID- 8579106
TI  - Expression of NF-kappa B and I kappa B-alpha by aortic endothelium in an arterial
      injury model.
AB  - Endothelial cells at sites of inflammatory responses express a variety of genes
      that are under the control of nuclear factor NF-kappa B, a transcription factor
      that with its inhibitors may be linked in an autoregulatory system that can be
      activated by multiple signals relevant to vascular pathophysiology. A model of
      limited endothelial denudation in the aorta of rats and mice was used to study
      the role of NF-kappa B and the inhibitor I kappa B-alpha Using en face techniques
      for in situ hybridization and immunostaining, normal endothelium showed diffuse
      cytoplasmic immunoreactivity for the NF-kappa B components p50 and p65 as well as
      the inhibitor I kappa B-alpha Within 45 minutes after wounding, nuclear staining
      for both NF-kappa B components was noticeable in the endothelial cells at the
      wound edge, which was followed by a dramatic induction of VCAM-1 mRNA and protein
      3 hours later. Leading edge endothelial cells also responded with up-regulated
      expression of both NF-kappa B components and I kappa B-alpha. The increased
      expression of p50, p65, VCAM-1, and I kappa B-alpha persisted in replicating
      endothelium that was associated with adhesion of monocyte/macrophages to these
      cells. Expression levels returned to normal after regeneration. Our data
      establish for the first time the presence of the NF-kappa B/I kappa B-alpha
      system in the vasculature and demonstrate a correlation between activation of the
      regulatory system and induction of a kappa B-dependent endothelial adhesion
      molecule in an animal model of arterial injury. This autoregulatory system may be
      an important homeostatic mechanism in the vessel wall.

PMID- 8579107
TI  - Identification of platelet-derived growth factor A and B chains in human renal
      vascular rejection.
AB  - Platelet-derived growth factor (PDGF) exists as a dimer composed of two
      homologous but distinct peptides termed PDGF-A and -B chains, and may exist as
      AA, AB, and BB isoforms. The PDGF-B chain has been implicated as a mediator of
      renal vascular rejection by virtue of up-regulated expression of its receptor,
      PDGF beta-receptor, in affected arteries. A role for PDGF-A chain in mediating
      intimal proliferation has been suggested in human atherosclerosis (Rekhter MD,
      Gordon D: Does platelet-derived growth factor-A chain stimulate proliferation of
      arterial mesenchymal cells in human atherosclerotic plaques? Circ Res 1994,
      75:410), but no studies of this molecule in human renal allograft injury have
      been reported to date. We used two polyclonal antisera to detect expression of
      PDGF-A chain and one monoclonal antibody to detect PDGF-B chain by
      immunohistochemistry in fixed, paraffin-embedded tissue from 1) normal adult
      kidneys, 2) a series of renal transplant biopsies chosen to emphasize features of
      vascular rejection, and 3) allograft nephrectomies. Immunohistochemistry was
      correlated with in situ hybridization on adjacent, formalin fixed tissue sections
      from nephrectomies utilizing riboprobes made from PDGF-A and -B chain cDNA. PDGF
      A chain is widely expressed by medial smooth muscle cells of normal and rejecting
      renal arterial vessels of all sizes by immunohistochemistry and in situ
      hybridization. PDGF-A chain is also expressed by a population of smooth muscle
      cells (shown by double immunolabeling with an antibody to alpha-smooth muscle
      actin) comprising the intima in chronic vascular rejection. In arteries
      demonstrating acute rejection, up-regulated expression of PDGF-A chain by
      endothelial cells was detected by both immunohistochemistry and in situ
      hybridization. In contrast, PDGF-B chain was identified principally in
      infiltrating monocytes within the rejecting arteries, similar to its localization
      in infiltrating monocytes in human atherosclerosis. Although less prominent than
      the case for PDGF-A chain, PDGF-B chain also was present in medial and intimal
      smooth muscle cells in both rejecting and nonrejecting renal arteries. PDGF-A and
      -B chains have now been localized at both the mRNA and protein levels to the
      intimal proliferative lesions of vascular rejection. These peptides, which are
      known stimuli for smooth muscle cell migration and proliferation in experimental
      vascular injury, may have similar stimulatory effects on smooth muscle cells in
      an autocrine and/or paracrine manner to promote further intimal expansion and
      lesion progression in this form of human vasculopathy.

PMID- 8579108
TI  - Expression of CD44 isoforms in renal cell tumors. Positive correlation to tumor
      differentiation.
AB  - CD44 isoforms have been implicated in tumor progression and embryogenesis.
      Primary renal cell tumors (n = 100) of various histopathological differentiation
      and grading stages were analyzed for expression of CD44 isoforms in comparison
      with nonmalignant adult and fetal renal tissues. Evaluations were performed by
      immunohistochemistry using CD44 isoform-specific monoclonal antibodies and by
      reverse transcriptase polymerase chain reactions (RT-PCR). In the nonmalignant
      kidney no CD44 variant isoforms were detected. There was a significant increase
      in expression of CD44 standard (CD44s) and several variant isoforms (CD44v) in
      the course of tumor differentiation in clear cell carcinomas (n = 68) from stages
      G1 to G3 (P < 0.0001 for CD44s and isoforms containing CD44-6v, and P < 0.007 for
      those containing CD44-9v). Also, in chromophilic cell carcinomas (n = 13), CD44
      isoform expression correlated with grading; ie, no CD44 expression was detected
      in G1 tumors, whereas in approximately 50% of the G2 tumors, CD44s, CD44-6v, and
      CD44-9v isoforms were present. Oncocytomas (n = 8), which are benign renal cell
      tumors, did not express CD44 isoforms, whereas invasive chromophobe cell
      carcinomas (n = 11) were positive for CD44s and CD44v isoforms. Transcript
      analyses by RT-PCR revealed that the upregulated isoforms in the carcinoma cells
      contained exons 8 to 10 and 3, 8 to 10 in combination from the variant region. In
      conclusion, expression of variant CD44 isoforms was strongly correlated with
      grading and appears to mediate a more aggressive phenotype to renal cell tumors.

PMID- 8579109
TI  - Intercellular adhesion molecule-3 on endothelial cells. Expression in tumors but
      not in inflammatory responses.
AB  - Intercellular adhesion molecule-3 (ICAM-3) was identified as the third counter
      receptor for lymphocyte function-associated antigen-1. ICAM-3 is absent on
      endothelial cells in normal tissues but found on endothelial cells in lymphomas.
      Here, we examined ICAM-3 expression on vascular endothelial cells in lymphomas,
      nonlymphoid malignancies, benign tumors, and inflammatory diseases. We compared
      the expression of ICAM-3 on endothelial cells with the severity of inflammatory
      infiltrates and with the presence of E-selectin and VCAM-1. We found that ICAM-3
      expression on endothelial cells was high on both benign and malignant tumors
      whereas it was low in inflammatory diseases. In contrast to E-selectin, ICAM-3
      expression on endothelial cells was not correlated to the severity of
      inflammatory infiltrates. In hemangiomas, we showed by Northern blot analysis and
      immunocytochemistry that ICAM-3 expression was induced and that it was localized
      in immature areas that sustain the early stages of angiogenesis. Therefore,
      expression of ICAM-3 on blood vessels does not seem to play a role in the
      recruitment of leukocytes during inflammation but rather is correlated with
      angiogenesis and tumor development.

PMID- 8579110
TI  - Hypoxic tumor cell death and modulation of endothelial adhesion molecules in the
      regression of granulocyte colony-stimulating factor-transduced tumors.
AB  - C-26 colon adenocarcinoma cells transduced with the granulocyte colony
      stimulating factor (G-CSF) gene form large tumors when injected into sublethally
      irradiated mice. These tumors regress when leukocyte function is reconstituted.
      Electron microscopy and immunocytochemical analysis of regressing C-26/G-CSF
      nodules indicates that tumor destruction is due mainly to hypoxia resulting from
      the functional loss of tumor vasculature and is only marginally due to direct
      cytolysis. Desegregation of basal lamina, cell swelling, and loss of junctions
      characterized the vessels within regressing tumors. Tumor cells were necrotic or
      filled with lipid vacuoles regardless of the distance from nearby vessels. Damage
      of tumor vasculature was dependent on the infiltrating leukocytes and the
      cytotoxic cytokines they produced. Locally produced interleukin-1 and tumor
      necrosis factor-alpha (TNF-alpha) induced vascular cellular adhesion molecule-1
      (VCAM-1) and E-selectin on tumor vessels. Treatment with monoclonal antibodies to
      interferon-gamma (IFN-gamma) or TNF-alpha blocked tumor regression by inhibiting
      VCAM-1 and E-selectin expression on tumor-associated endothelial cells resulting
      in a reduced number of infiltrating leukocytes. Thus, C-26/G-CSF tumor regression
      presents features typical of hemorrhagic necrosis that occurs through the
      cytokines produced by infiltrating leukocytes in response to G-CSF.

PMID- 8579111
TI  - Tumor necrosis factor-alpha-induced apoptosis in hepatocytes in long-term
      culture.
AB  - Apoptosis occurs naturally in the liver and increases in specific pathogenic
      processes. We previously described the use of a chemically defined medium
      supplemented with epidermal growth factor and dimethylsulfoxide to maintain rat
      hepatocytes in a highly differentiated state for more than 30 days (long-term
      culture). In this study, we showed that hepatocytes in long-term
      dimethylsulfoxide culture have definite advantages over using cells in short-term
      culture (cells in culture for 2 to 4 days) to study apoptosis. We demonstrated
      that treatment with tumor necrosis factor (TNF)-alpha induced apoptosis (detected
      morphologically and by formation of an oligonucleosomal DNA ladder) only in
      hepatocytes that had been subjected to dimethylsulfoxide removal. Neither
      treatment with TNF-alpha alone or dimethylsulfoxide removal alone induced
      apoptosis. Apoptosis could be induced by concentrations as low as 500 U of TNF
      alpha/ml. Although a DNA ladder was not detected by 12 hours after TNF-alpha
      treatment, it was easily identified by 24 hours. We conclude that this system can
      be used 1) to examine the underlying mechanism by which TNF-alpha causes
      apoptosis in hepatocytes and 2) to study induction of apoptosis in hepatocytes by
      other agents.

PMID- 8579112
TI  - Temporal cell-type-specific mRNA expression of O6-methylguanine-DNA
      methyltransferases in liver of rats treated with dimethylnitrosamine.
AB  - The intercellular distribution of O6-methylguanine-DNA methyltransferase (MGMT)
      mRNA expression has been investigated at the individual cell level in the liver
      of rats treated with dimethylnitrosamine using in situ hybridization. Male BDIV
      rats were orally administered with a single dose of dimethylnitrosamine (5 or 10
      mg/kg) and were killed at 24, 48, and 96 hours after exposure. Constitutive MGMT
      mRNA expression was found in bile duct cells, vascular endothelial cells, and
      fibrous cells; however, weak or negative expression was detected in hepatocytes
      and Kupffer cells. On the other hand, after exposure to dimethylnitrosamine,
      inducible MGMT mRNA was rapidly expressed in hepatocytes, especially in the
      centrilobular area at earlier time points, confirming our previous studies in
      which enzymatic activity has been measured in different purified cell populations
      obtained by differential centrifugation. Immunohistochemical detection of the O6
      methylguanine-DNA adduct formation was demonstrated in a dose-dependent fashion
      and was mainly found in the centrilobular hepatocytes where high levels of MGMT
      mRNA were present. These results suggest a correlation between the induction of
      this repair activity and DNA damage; however, the relationship between MGMT mRNA
      and enzyme activity remains to be fully established for all cell types.

PMID- 8579113
TI  - Autoimmunity in chronic active Helicobacter hepatitis of mice. Serum antibodies
      and expression of heat shock protein 70 in liver.
AB  - Male A/JCr mice with naturally occurring Helicobacter hepaticus infection develop
      a progressive chronic active hepatitis and liver tumors, despite the presence of
      serum antibodies to Helicobacter proteins. A rabbit antiserum prepared against
      the bacterial proteins immunoreacted with hepatocytes present in liver sections
      from infected mice with progressive lesions. We found that sera from these mice
      contained IgG antibodies that reacted in immunoblots with recombinant heat shock
      protein 70 (DmaK from Escherichia coli) but not with heat shock protein 60
      (GroEL) or heat shock protein 10 (GroES). A rabbit antibody to heat shock protein
      70 reacted with H. hepaticus in tissue sections and to a H. hepaticus protein (70
      kd) in Western blots. Immunohistochemistry and in situ hybridization for heat
      shock protein 70 revealed that individual hepatocytes and other cells expressed
      the protein in livers with hepatitis but not usually in normal livers. Liver
      tumors and preneoplastic lesions in infected mice did not usually express heat
      shock protein 70 except focally in a few tumors. In situ hybridization for H.
      hepaticus 16S rRNA showed that the bacteria was found throughout the liver
      associated with hepatitis but not within tumors. CD3+ T lymphocytes were found in
      close association with hepatic lesions. These data suggest a role for
      autoimmunity in progressive hepatitis and carcinogenesis in livers infected with
      H. hepaticus.

PMID- 8579114
TI  - Enhanced expression of matrilysin, collagenase, and stromelysin-1 in
      gastrointestinal ulcers.
AB  - Programmed expression of several matrix metalloproteinases is an important
      feature of cutaneous wound healing. To study whether this also applies to
      gastrointestinal ulcer healing, we used in situ hybridization with 35S-labeled
      probes to localize sites of collagenase, stromelysin-1, and matrilysin expression
      in 26 samples representing peptic ulcers, Crohn's disease, and ulcerative
      colitis. In contrast to skin wounds, collagenase mRNA was not detected in the
      surface epithelium bordering gastrointestinal ulcer areas. However, together with
      stromelysin-1 mRNA, it was abundantly expressed by the granulation tissue in all
      types of ulcers. Signal for matrilysin mRNA and protein was detected in the
      mucosal epithelium bordering the ulcerations but never in the ulcer stroma. The
      gut basement membrane was disrupted under the matrilysin-producing epithelial
      cells as assessed by immunostaining for laminin. Tissue inhibitor of
      metalloproteinases (TIMP-1) mRNA never co-localized with matrilysin-positive
      mucosal epithelial cells. These data indicate that matrilysin plays a significant
      role in epithelial remodelling occurring in gastrointestinal ulcerations whereas
      collagenase and stromelysin-1 are involved in the reparative processes in the
      ulcer bed.

PMID- 8579116
TI  - Expression of mRNAs for type I and type III procollagens in serous ovarian
      cystadenomas and cystadenocarcinomas.
AB  - Malignant ovarian tumors induce a strong fibro-proliferative reaction
      characterized by the active production of type I and type III procollagen both
      locally in the ovary as well as more remotely in the peritoneal cavity. Our
      purpose was to determine the origin of the increased collagen production observed
      in serous ovarian tumors with different histological grades of malignancy, ie,
      whether the malignant cells or the stromal fibroblasts are responsible for the
      synthesis of collagen fibers. We visualized the mRNAs corresponding to the pro
      alpha 1(I) and pro alpha 2(I) chains of type I procollagen and the pro alpha
      1(III) chain of type III procollagen by in situ hybridization. Strong signals for
      both chains of type I procollagen were seen in stromal fibroblasts next to tumor
      cell islets, whereas the reaction was weak or absent near benign ovarian cysts.
      In poorly differentiated tumors, the signals were particularly abundant and
      occasionally also seen in the neoplastic cells themselves. Type III procollagen
      mRNA expression was similar, although somewhat less distinct. These findings
      indicate that the production of interstitial procollagens is related to the
      degree of malignancy and neoplastic activity of tumors. The formation of collagen
      in well differentiated ovarian tumors is a function of stromal fibroblasts,
      whereas in poorly differentiated tumors, aberrant expression of one or several
      chains of type I and type III procollagens in the neoplastic cells is also likely
      to take place.

PMID- 8579115
TI  - Lung fibroblast alpha-smooth muscle actin expression and contractile phenotype in
      bleomycin-induced pulmonary fibrosis.
AB  - The emergence of the myofibroblast phenotype (characterized by alpha-smooth
      muscle actin expression) in wound healing and in tissues undergoing fibrosis is
      thought to be responsible for the increased contractility of the affected
      tissues. In bleomycin-induced pulmonary fibrosis, the myofibroblast is also
      responsible for the observed increase in collagen gene expression. To evaluate
      further these phenotypic changes in lung fibroblasts, contractile and other
      phenotypic properties of fibroblasts isolated from lungs of rats with bleomycin
      induced fibrosis were compared with those of normal rats using in vitro models.
      Pulmonary fibrosis was induced in rats by endotracheal injection on day 0, and 7
      and 14 days later the animals were sacrificed and lung fibroblasts isolated.
      Using immunofluorescence, < 10% of fibroblasts from control animals express alpha
      smooth muscle actin when cultured as a monolayer. In contrast, 19% and 21% of
      cells from day 7 and day 14 bleomycin-treated animals, respectively, expressed
      this actin and with greater intensity than in control lung cells. This increase
      in actin expression was associated with enhanced contractility when evaluated
      using a three-dimensional cell culture model consisting of fibroblast-populated
      collagen gels. This enhanced contractility was abolished by treatment with
      antibody to transforming growth factor-beta (TGF-beta), whereas exogenous TGF
      beta 1 and serum-stimulated contraction of control lung fibroblasts. TGF-beta 1
      gene expression was greater in cells from bleomycin-treated animals than those
      from control lungs. These results show that cells with the myofibroblast
      phenotype are more abundant in fibrotic lung, and that these cells possess
      greater contractile capacity in vitro at least partly by virtue of their enhanced
      endogenous TGF-beta 1 gene expression.

PMID- 8579118
TI  - Interphase fluorescence in situ hybridization and reverse transcription
      polymerase chain reaction as a diagnostic aid for synovial sarcoma.
AB  - Identification of the t(X;18)(p11.2;q11.2) that is associated with a high
      proportion of synovial sarcoma can be a useful diagnostic aid. The translocation
      results in fusion of the SYT gene on chromosome 18 to either the SSX1 or the SSX2
      gene, two homologous genes within Xp11.2. Two-color interphase fluorescence in
      situ hybridization and reverse transcription polymerase chain reaction were
      assessed as approaches to identify the rearrangement in well characterized cases.
      The presence of the translocation, and the specific chromosome X gene disrupted,
      were inferred from the configuration of signals from chromosome-specific
      centromere probes, paints, and markers flanking each gene in preparations of
      interphase nuclei. Rearrangement was found in two cell lines and eight of nine
      tumor samples, including analysis of five touch imprints. This was consistent
      with cytogenetic data in four cases and reverse transcription polymerase chain
      reaction analysis using primers known to amplify both SYT-SSX1 and SYT-SSX2
      transcripts. The transcripts were distinguished by restriction with LspI and
      SmaI. Contrary to previous suggestions, there was no obvious correlation between
      histological subtype and involvement of the SSX1 or SSX2 gene. These approaches
      could also be applied to the identification of tumor-free margins and metastatic
      disease.

PMID- 8579117
TI  - Type 1 receptor tyrosine kinases are differentially phosphorylated in mammary
      carcinoma and differentially associated with steroid receptors.
AB  - The neu/erbB-2/HER-2 proto-oncogene is amplified and/or overexpressed in up to
      30% of mammary carcinomas and has been variably correlated with poor prognosis.
      The signaling activity of the encoded receptor tyrosine kinase is regulated by
      interactions with other type 1 receptors and their ligands. We have used a novel
      approach, phosphorylation-sensitive anti-Neu antibodies, to quantify signaling by
      Neu and epidermal growth factor receptor in a panel of frozen sections of mammary
      carcinoma specimens. We also determined the relationship of Neu, phosphorylated
      Neu (and epidermal growth factor receptor), and phosphotyrosine to the expression
      of Neu-related receptors (epidermal growth factor receptor, HER-3, and HER-4) and
      to prognostic factors (estrogen and progesterone receptor). We found that
      tyrosine phosphorylation of Neu (and hence signaling activity) is highly variable
      among mammary carcinomas. Neu and HER-4 were associated with divergent
      correlates, suggesting that they have profoundly different biological activities.
      These results have implications for etiology of mammary carcinoma for clinical
      evaluation of mammary carcinoma patients, and for development of Neu-targeted
      therapeutic strategies.

PMID- 8579119
TI  - Matrix proteins with high affinity for calcium ions are associated with
      mineralization within the elastic fibers of pseudoxanthoma elasticum dermis.
AB  - Ultrathin sections from the dermis of five normal subjects and from 10 patients
      suffering from pseudoxanthoma elasticum (PXE) were analyzed by immunoelectron
      microscopy with the aim of identifying and localizing proteins associated with
      the mineral precipitates within the altered elastic fibers. Serial sections were
      processed by indirect immunogold cytochemistry using primary antibodies against
      human fibronectin, vitronectin, bone sialoprotein, alkaline phosphatase,
      osteonectin, and osteopontin. In the latter two cases, antibodies against
      synthetic peptides were also used. The results indicate that normal elastic
      fibers contained osteopontin, and that this protein was associated with the
      apparently normal elastin as well as with the needle-shaped mineral precipitates
      in the elastic fibers of patients. On the contrary, significant amounts of
      vitronectin, alkaline phosphatase and, less, of bone sialoprotein were associated
      with the polymorphous mineral precipitates inside the elastic fibers. Large
      amounts of osteonectin and fibronectin, together with vitronectin, were localized
      on the microfilament aggregates, which were often associated with altered elastic
      fibers in PXE dermis and were never visualized in the dermis of control subjects.
      The results seem to indicate once more that PXE is a complex disorder of the
      fibroblast synthetic control. Elastic fiber mineralization might be considered a
      secondary event, which could depend on the abnormal synthesis and accumulation
      within the elastic fibers of proteins that are normally involved in
      mineralization processes.

PMID- 8579120
TI  - Expression of fibronectin ED-A+ and ED-B+ isoforms by human and experimental
      colorectal cancer. Contribution of cancer cells and tumor-associated
      myofibroblasts.
AB  - Alternative splicing of primary fibronectin (FN) mRNA results in the synthesis of
      different isoforms. ED-A+ and ED-B+ FN isoforms are absent from plasma FN and are
      representative of cellular FN. Their expression was studied in human and rat
      normal colon, in human colorectal carcinomas, and in transplanted tumors derived
      from a chemically-induced rat colon cancer. In normal colon, only the ED-A+ FN
      isoform was expressed as a thin deposit between crypt colonocytes and pericryptal
      myofibroblasts. Conversely, heavy ED-A+ FN deposits and lighter ED-B+ FN
      expression were found in the stroma of colorectal tumors in association with
      myofibroblasts surrounding tumor glands. Some colonic cancer cells also contained
      intracellular FN isoform granules and expressed FN mRNA. Tumor-associated
      myofibroblasts and some cancer cell lines were able to synthesize and deposit
      extracellular ED-A+ and ED-B+ FN in vitro. FN isoform deposition by tumor
      associated myofibroblasts was not modulated by colon cancer cell-conditioned
      medium, but was strongly enhanced when myofibroblasts were cultured on colon
      cancer cell extracellular matrix or on laminin. These results show that the ED-A+
      and ED-B+ FN isoforms were overexpressed in colorectal cancer. Cancer cells can
      deposit these FN isoforms directly and also stimulate their deposition by tumor
      associated myofibroblasts.

PMID- 8579121
TI  - Circulating human dendritic cells differentially express high levels of a 55-kd
      actin-bundling protein.
AB  - This study was initiated to examine the differential expression of an
      evolutionary conserved human 55-kd actin-bundling (p55) protein that is induced
      in B lymphocytes by Epstein-Barr virus infection. Our study demonstrates that p55
      is specifically expressed at constitutively high levels in human peripheral blood
      dendritic cells and lymph node (interdigitating) dendritic cells. Blood dendritic
      cells constitute a minority (< 2%) of all blood leukocytes but are a distinct
      population of potent antigen-presenting cells. Immunofluorescence microscopy with
      a monoclonal antibody specific for p55 showed that 87% of peripheral blood
      dendritic cells stained brightly in the cytoplasm and in the veiled cytoplasmic
      extensions. In contrast, monocytes, granulocytes, T cells, and B lymphocytes
      showed no expression of the p55 protein. Western blot analysis confirmed that
      only the dendritic cell component of peripheral blood expressed high levels of
      p55. Staining of human lymph node sections demonstrated selective expression of
      the p55 antigen by dendritic cells in the T-cell-dependent areas but not in the B
      cell follicles. p55 is likely to be involved in the organization of a specialized
      microfilament cytoskeleton in the dendritic cells, and the anti-p55 antibody
      should be useful for further characterization of this important population of
      antigen-presenting cells in clinical transplantation, HIV-1 pathogenesis, and
      autoimmune diseases.

PMID- 8579122
TI  - Chromosomal translocation t(X;18) in human synovial sarcomas analyzed by
      fluorescence in situ hybridization using paraffin-embedded tissue.
AB  - Synovial sarcoma is characterized cytogenetically by translocation
      t(X;18)(p11.2;q11.2). In this study, 28 cases that had been diagnosed initially
      as synovial sarcoma, including 2 fibrosarcomas, and 1 leiomyosarcoma were
      collected and examined for translocation t(X;18) on paraffin-embedded tissues by
      fluorescence in situ hybridization (FISH). Of the synovial sarcomas, 25 showed
      findings consistent with translocation t(X;18) with an additional copy signal for
      the total probe of X and 18 chromosomes. The other three cases, as well as the
      two fibrosarcomas and the leiomyosarcoma, did not show this translocation. One
      (case 26) of three negative cases was diagnosed finally as leiomyosarcoma and
      another (case 27) as malignant peripheral nerve sheath tumor from histological
      and immunohistochemical analysis. Thus, in all, 25 (96%) of 26 synovial sarcomas
      showed findings consistent with translocation t(X;18). In summary, translocation
      t(X;18) is a chromosomal aberration specific for synovial sarcoma. The
      fluorescence in situ hybridization technique can be used even on cells from
      paraffin-embedded tissues, and is a useful diagnostic aid for synovial sarcoma.

PMID- 8579124
TI  - Correlation between clinicopathological features and karyotype in lipomatous
      tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP)
      Collaborative Study Group.
AB  - Soft tissue tumors commonly show cytogenetic abnormalities, some of which are
      tumor specific. Lipomatous tumors represent the largest category of soft tissue
      neoplasms, and numerous karyotypic aberrations have been identified. However,
      clear-cut correlation between morphology and karyotype has not been undertaken on
      a systematic basis in a double-blind setting. The morphological features and
      histological diagnosis of 178 lipomatous neoplasms were reviewed independently
      without knowledge of the clinical data. The consensus diagnoses were then
      correlated with the clinical findings and compared with the tumors' karyotypes,
      using G-banded preparations from short-term cultures. The data were collated by a
      multicenter collaborative group of pathologists, geneticists, and surgeons.
      Clonal chromosomal abnormalities were identified in 149 cases studied (84%) and,
      to a large extent, the karyotype correlated with the morphological diagnosis.
      Specifically, 26 (96%) of 27 myxoid liposarcomas and its poorly differentiated
      variants showed a t(12;16); 29 (78%) of 37 atypical lipomatous tumors (including
      5 dedifferentiated cases) showed ring chromosomes; 74 (80%) of 93 subcutaneous
      and intramuscular lipomas had karyotypic aberrations affecting mainly 12q, 6p,
      and 13q; 7 of 8 spindle cell and pleomorphic lipomas had aberrations of 16q; 3
      lipoblastomas showed 8q rearrangements; and 2 hibernomas showed 11q
      abnormalities. We conclude that cytogenetic abnormalities are common in
      lipomatous tumors, correlate reliably with morphological sub-type in many cases,
      and can be of diagnostic value in histologically borderline or difficult cases.

PMID- 8579123
TI  - Matrix metalloproteinase 9 (gelatinase B) is expressed in multinucleated giant
      cells of human giant cell tumor of bone and is associated with vascular invasion.
AB  - Human giant cell tumor (GCT) consists of multinucleated giant cells and
      mononuclear stromal cells, and is characterized by frequent vascular invasion
      without distant metastases. To study the role of matrix metalloproteinases (MMPs)
      in the vascular invasion, we examined production of MMP-1 (tissue collagenase), 
      2 (gelatinase A), -3 (stromelysin-1), -9 (gelatinase B), and tissue inhibitors of
      metalloproteinases (TIMP-1 and -2) in GCT. MMP-9 was highly and predominantly
      expressed in giant cells by both immunohistochemistry and in situ hybridization.
      Expression of other MMPs was also observed in some cases but was inconstant.
      Sandwich enzyme immunoassays demonstrated that MMP-9 is the predominant MMP
      secreted by GCT. There was a definite imbalance between the amounts of MMP-9 and
      those of TIMPs in the culture media of GCT, leading to detectable gelatinolytic
      activity in an assay using 14C-gelatin. Gelatin zymography demonstrated the main
      activity at about 90 kd, which was identified as the zymogen of MMP-9 by
      immunoblotting. Immunohistochemistry for type IV collagen and laminin, major
      basement membrane components, showed that disappearance of the proteins is
      closely associated with MMP-9-positive giant cells. These results indicate the
      production of MMP-9 by multinucleated giant cells and suggest that the
      metalloproteinase may contribute to proteolysis associated with vascular invasion
      and local bone resorption in human GCT.

PMID- 8579125
TI  - Photoreceptor apoptosis induced by a single systemic administration of N-methyl-N
      nitrosourea in the rat retina.
AB  - Retinal degeneration was induced by a single intraperitoneal injection of N
      methyl-N-nitrosourea in female Sprague-Dawley albino rats at 50 days of age by
      two dose regimens, which were observed sequentially at 24, 48, and 72 hours and
      7, 21, and 35 days after the treatment. After a dose of 75 mg/kg,
      methylnitrosourea evoked progressive retinal degeneration in all treated rats
      whereas a dose of 50 mg/kg was less effective. The 75-mg/kg-treated rats showed
      selective destruction of the photoreceptor cells by an apoptotic mechanism, as
      confirmed morphologically and by the terminal dUTP nick end labeling method.
      Apoptosis had already started at 24 hours after the treatment and was completed
      by day 7. During the photoreceptor degeneration, proliferation of glial
      fibrillary acidic protein and vimentin-positive Muller cells as detected by
      proliferating cell nuclear antigen labeling appeared at 48 hours and was
      prominent 72 hours after the treatment, and macrophage infiltration within the
      retina as recognized by ED1 positivity was maximal 7 and 21 days after the
      treatment. Retinal degeneration was also induced in female Brown-Norway colored
      rats in a similar dose-dependent manner. Pigment epithelium was discontinuous
      above Bruch's membrane, and migration of the swollen pigment epithelium toward
      the inner nuclear layer was seen 7 days after the treatment. Therefore, as also
      confirmed electron microscopically, the most striking change was the destruction
      of photoreceptor cells by the apoptotic process, followed by Muller cell
      proliferation, pigment epithelium migration, and macrophage infiltration for cell
      debris phagocytosis, resulting in a thin remnant of retina with attenuated inner
      nuclear cells in direct contact with Bruch's membrane or with the pigment
      epithelium and/or with the Muller cells 35 days after the treatment.

PMID- 8579126
TI  - Replication error phenotype and p53 gene mutation in lymphomas of mucosa
      associated lymphoid tissue.
AB  - Low grade mucosa-associated lymphoid tissue (MALT) lymphomas commonly arise from
      a background of chronic inflammatory lesions and can transform into high grade
      tumors at a late stage. Because chronic inflammation is closely associated with
      genetic instability, which is one of the mechanisms leading to activation of
      oncogenes and inactivation of tumor suppressor genes, it is possible that genetic
      instability plays an important role in MALT lymphomagenesis. In this study, we
      have examined the frequency of replication error (RER+) phenotype, a newly
      defined manifestation of genetic instability, and its relationship to p53
      mutations in 40 MALT lymphomas (16 high grade and 24 low grade). RER+ phenotype
      was detected in 21/40 (52.5%) MALT lymphomas (12/24, 50% in low grade; 9/16,
      56.2% in high grade). Five of seven reactive lymphoid infiltrates adjacent to
      tumors also showed one microsatellite alteration, four of which were identified
      in the corresponding lymphoma lesions in the same patient. In five RER+ high
      grade lymphomas with low grade lesions, homogeneous and heterogeneous
      microsatellite alterations were observed between the two components. The same 40
      cases were investigated for p53 gene mutations at exons 5 to 8 by PCR-SSCP and
      direct sequencing. p53 point mutations were found in 11 (27.5%) of the 40 cases.
      These mutations were statistically related to RER+ phenotype (P < 0.05). Our
      results demonstrate that the RER+ phenotype is a common genetic feature of MALT
      lymphomas. Genetic instability occurs throughout the spectrum of the lymphoma
      development and may be related to the accumulation of genetic aberrations such as
      p53 mutations. The observation of identical microsatellite alterations between
      the adjacent lymphoid infiltrates and their corresponding lymphomas provides
      genetic evidence for evolutionary link of the two lesions. The homogeneous and
      heterogeneous microsatellite alterations observed between low and high grade
      components indicate their clonal lineage and genetic diversity.

PMID- 8579127
TI  - Detection of breast cancer micrometastases in axillary lymph nodes by means of
      reverse transcriptase-polymerase chain reaction. Comparison between MUC1 mRNA and
      keratin 19 mRNA amplification.
AB  - Usefulness of MUC1 mRNA and keratin 19 mRNA as a target of reverse-transcriptase
      polymerase chain reaction (RT-PCR) was compared in the detection of breast cancer
      micrometastases in axillary lymph nodes. RT-PCR amplification of MUC1 mRNA and
      keratin 19 mRNA was conducted using total RNA samples. RT-PCR products were
      stained with ethidium bromide and analyzed by agarose gel electrophoresis.
      Expression of both MUC1 mRNA and keratin 19 mRNA was detected by RT-PCR in a
      breast cancer cell line (MRK) and in all the 23 primary breast cancers but not in
      the control lymph nodes obtained from patients with benign diseases. A serial
      dilution study of MRK cells against normal lymph node cells has shown that
      detection sensitivity of MUC1 RT-PCR and keratin 19 RT-PCR were 1/10(5) and
      1/10(6) (cancer/lymph node cells), respectively. Sixty-three axillary lymph nodes
      were obtained from 23 patients with primary breast cancer, and metastases in each
      lymph node were investigated by histological examination (hematoxylin and eosin
      sections) and RT-PCR method. In all 10 lymph nodes, which were histologically
      metastasis-positive, both MUC1 mRNA and keratin mRNA were detected by RT-PCR. Of
      the 53 histologically negative lymph nodes, 3 (6%) and 5 (9%) lymph nodes were
      found to express MUC1 mRNA and keratin 19 mRNA, respectively, indicating the
      presence of micrometastases which could be detected by RT-PCR but not by
      histological examination. These results demonstrate the usefulness of both MUC1
      RT-PCR and keratin 19 RT-PCR in the detection of breast cancer micrometastases in
      lymph nodes, and also indicate the superiority of keratin 19 RT-PCR over MUC1 RT
      PCR because of its higher detection sensitivity.

PMID- 8579128
TI  - Sequestration of inhaled particulate antigens by lung phagocytes. A mechanism for
      the effective inhibition of pulmonary cell-mediated immunity.
AB  - Dendritic cells (DCs) have emerged as the dominant antigen-presenting cells
      (APCs) of the lung, playing a vital role in the induction of cell-mediated
      immunity to inhaled antigens. We have previously demonstrated that an airway
      challenge with the soluble antigen hen egg lysozyme yields rapid acquisition of
      specific antigen-presenting cell activity by purified pulmonary DCs and a cell
      mediated immune response in the lung upon secondary challenge. To examine how a
      particulate antigen leads to a cell-mediated response in vivo, graded
      concentrations of heat-killed Listeria (HKL) were injected intratracheally into
      Lewis rats. The bacteria were rapidly ingested by lung macrophages and
      polymorphonuclear leukocytes. The ability of purified pulmonary DCs pulsed in
      vivo by an airway challenge with HKL to subsequently stimulate HKL-specific
      responses ex vivo showed a threshold response, requiring a dose in excess of
      10(9) organisms/rat. By contrast, all dosages of HKL yielded specific
      sensitization of lymphocytes in the draining bilar nodes. Pulmonary DCs purified
      from rats after a secondary in vivo airway challenge with HKL at day 14 were
      ineffective antigen-presenting cells except at high dosages of antigen. The
      generation of cell-mediated pulmonary inflammation paralleled the antigen
      presenting cell activity of pulmonary DCs and was observed only at high antigen
      dosages. Hen egg lysozyme immobilized onto polystyrene beads and injected
      intratracheally yielded comparable results to those observed with HKL. We suggest
      that a pulmonary cellular immune response is generated to an inhaled particulate
      antigen when the protective phagocytic capacities of the lung are exceeded and
      antigen is able to interact directly with interstitial DCs. The diversion of
      particulate antigens by pulmonary phagocytes may help to limit undesirable
      pulmonary inflammation while allowing the generation of antigen-specific immune
      lymphocytes in vivo.

PMID- 8579130
TI  - Proposal of a guideline in reporting hearing results in middle ear and mastoid
      surgery.

PMID- 8579129
TI  - Experimental rabbit models of Chlamydia pneumoniae infection.
AB  - Chlamydia pneumoniae (TWAR), a common cause of acute respiratory disease in
      humans, has recently been associated with coronary and aortic atherosclerosis. In
      this study, we evaluated rabbit models of chlamydial infection to investigate the
      pathogenesis of C. pneumoniae infection. New Zealand White rabbits were
      inoculated intranasally and intratracheally with C. pneumoniae, strain AR-39, and
      primary and repeated infection were assessed. After a single inoculation, lung
      pathology was characterized by a moderate self-resolving interstitial pneumonia
      with bronchiolitis of 21 days in duration. Chlamydial DNA was detected by
      polymerase chain reaction (PCR) intermittently in the upper respiratory tract and
      lung tissue through day 21 postinoculation, spleen tissue at day 14, and
      peripheral blood mononuclear cells at days 3 and 21. After repeated inoculations,
      chlamydial DNA was detected by PCR in the upper respiratory tract and lung tissue
      through day 42. Lung lesions consisted of multifocal interstitial mononuclear
      cell aggregates that persisted up to day 42. Watanabe heritable hyperlipidemic
      rabbits were less susceptible to C. pneumoniae infection. After multiple
      inoculations of Watanabe rabbits, C. pneumoniae was detected by PCR and/or
      immunocytochemistry until day 21. In conclusion, C. pneumoniae induced a moderate
      respiratory infection in these rabbit models.

PMID- 8579131
TI  - Proliferating cell nuclear antigen in the determination of growth rates in
      acoustic neuromas.
AB  - The growth rate of acoustic neuromas is difficult to predict clinically; however,
      the ability to do so would be of benefit to the clinician for patient
      prognostication. Laboratory studies utilizing flow cytometry and immunologic
      methods have been used to investigate growth rates of acoustic neuromas. The
      purpose of this pilot immunohistochemical study, using proliferating cell unclear
      antigen (PCNA) on 22 randomly selected vestibular schwannomas, was to compare the
      growth factors, determined immunohistochemically, with the growth rate in this
      class of lesions. Proliferating cell nuclear antigen is an antibody against DNA
      polymerase delta, which is expressed in late G1 through S phase of the cell
      cycle. The advantage of using PCNA is that standard archival formalin-fixed,
      paraffin-embedded tissues may be analyzed and that PCNA detect cells in G1
      through S phase, allowing S-phase fractions, determined by flow cytometry.
      Results indicate that PCNA immunohistochemical analysis may potentially offer
      prognostic information relating to the growth potential of each tumor for
      individual patients with vestibular schwannomas. Further study with an expanded
      patient population is planned

PMID- 8579132
TI  - Epinephrine-induced changes in human cochlear blood flow.
AB  - Cochlear blood flow (CBF) was monitored over the basal turn stria vascularis
      using laser Doppler flowmetry in five human subjects during middle ear surgery.
      The effects of systemically administered epinephrine (0.3 microgram/kg) and
      topically applied epinephrine (1:10,000) on the round window membrane (RWM) were
      examined. Topical epinephrine caused a mean reduction of 60 percent in CBF
      (maximum peak reduction 65-85% across subjects), which slowly recovered ( > 10
      min) toward baseline following epinephrine removal from the RWM. The changes in
      CBF are similar to those found in animal studies, but are much larger, indicating
      a relatively more pronounced role of adrenergic agents in CBF control in humans.
      Systemic epinephrine caused a 40 percent decrease in skin blood flow, a 90
      percent increase in blood pressure (BP), above a resting hypotensive mean level
      of 65 mmHg, and a 50 percent increase in CBF. The CBF change followed the change
      in BP, but recovered toward baseline more slowly. The dramatic and somewhat
      prolonged decreases in CBF with RWM application of epinephrine may compromise
      sensory function and could account for the occasional unexplained sensorineural
      hearing loss or tinnitus associated with middle ear procedures that use topical
      epinephrine. The semipermeability of the RWM may, on the other hand, offer a
      route for therapeutic increases in CBF with vasodilative agents and provide an
      appropriate treatment for some cases of sensorineural hearing loss.

PMID- 8579133
TI  - Facial nerve neuromas presenting as acoustic tumors.
AB  - Facial nerve tumors can present as masses in the internal auditory canal or
      cerebellopontine angle and may mimic an acoustic neuroma. These tumors can occur
      in any segment of the nerve from the brain stem to the neuromuscular junction.
      Prior to the advent of computed tomography and magnetic resonance imaging with
      gadolinium, facial nerve tumors were often difficult to diagnose. Even with these
      modalities it may be difficult to distinguish preoperatively between an acoustic
      neuroma and a facial schwannoma. Particular signs and symptoms associated with
      facial nerve tumors (in the spasms, and a facial tic. These symptoms, combined
      with modem radiologic studies, should allow for more accurate diagnosis, patient
      counseling, and treatment. This report presents a series of 32 facial nerve
      tumors diagnosed and treated at The Otology Group from 1975 to 1992. Of these
      lesions, 12 (38%) were thought to be acoustic neuromas. Eighteen tumors were
      correctly identified preoperatively as facial nerve tumors. Two facial nerve
      tumors were found incidentally.

PMID- 8579134
TI  - Chronic otitis media after tympanostomy tube placement caused by Mycobacterium
      abscessus: a new clinical entity?
AB  - Infections with nontuberculous mycobacteria (NTM) are being identified with
      increasing frequency, but the otologic manifestations of NTM infection are not
      well defined. Mycobacterium abscessus is a ubiquitous rapidly growing
      mycobacterium (RGM) known to cause disease by inoculation after trauma. Though
      reported following open heart and breast augmentation surgery, it is not
      recognized as a cause of sporadic post-tympanostomy tube otorrhea. This report
      presents detailed clinical information on six sporadic cases and partial
      information on 15 additional cases of ear infection caused by RGM over the past 7
      years. Of these, 20 of 21 cases (95%) were attributable to M. abscessus, 14 of 21
      (67%) subjects lived in a southern coastal state and 16 of 16 with available
      histories had previously undergone placement of tympanostomy tubes. Each isolate
      exhibited resistance to many antibiotics, with 50 percent exhibiting high level
      mutational resistance to aminoglycosides related to prior topical aminoglycoside
      use. Therapy was difficult, requiring debridement and prolonged antibiotic
      therapy. M. abscessus is a problematic infection requiring specific diagnosis and
      treatment and should be sought as a cause of refractory post-tympanostomy tube
      otorrhea.

PMID- 8579135
TI  - Benign paroxysmal positional vertigo: analysis of 44 cases treated by the
      canalith repositioning procedure of Epley.
AB  - Between September 1987 and February 1993, the authors treated 44 consecutive
      cases of benign paroxysmal positional vertigo with the canalith repositioning
      procedure of Epley. The authors report a success rate of 87.7 percent using this
      treatment technique. Clinical observations and case reports are presented.

PMID- 8579136
TI  - Laser Doppler measurements of intratemporal facial nerve blood flow.
AB  - Whereas the anatomy of the vasculature supplying the intratemporal facial nerve
      is well known, little is known of the dynamics of blood flow within the nerve.
      The present study was performed to ascertain whether laser Doppler flowmetry
      (LDF) could detect changes in blood flow within the tympanic segment of the
      rabbit facial nerve. Compression of the facial nerve immediately distal to the
      geniculate ganglion resulted in an 80-95 percent reduction in blood flow in the
      tympanic segment of the nerve, whereas distal neurovascular compression had no
      effect. Blood flow in the tympanic segment of the nerve fell 40-60 percent during
      ipsilateral common carotid artery occlusion, but no change occurred with
      contralateral carotid occlusion. Signal-averaging techniques detected a
      sinusoidal amplitude modulation of the LDF flow signal that was synchronous with
      the cardiac cycle. The peak-to-peak amplitude of this modulation was reduced by
      proximal nerve compression, and the reduction in amplitude was in proportion to
      the overall reduction in the LDF flow signal. The authors conclude that the
      direction of blood flow in the tympanic segment of the rabbit facial nerve is
      primarily proximal to distal. Acute changes in blood flow within the tympanic
      segment of the nerve could readily be detected using LDF. This technique offers
      the possibility of monitoring human facial nerve blood flow, and may help
      elucidate the pathophysiology of various facial neuropathies.

PMID- 8579137
TI  - Stereolithographic model construction from CT for assessment and surgical
      planning in congenital aural atresia.
AB  - Surgical planning for the treatment of congenital aural atresia has depended
      greatly on the use of high resolution computerized tomography (CT) and, recently,
      three-dimensional CT for visual representation of the complex anatomy associated
      with this condition. Computerized plastic model construction, stereolithography,
      allows the digital data obtained through CT scanning to produce a life-size
      anatomically accurate plastic model of the structure scanned. When this technique
      is applied to congenital aural atresia there is good bony surface rendering as
      well as complete representation of the deeper structures contained within the
      temporal bone, including the middle ear cleft, ossicular mass, and fallopian
      canal. The surgeon can use this model to augment imaging in becoming familiar
      with the patient's unique anatomy and to practice a planned surgical procedure.

PMID- 8579139
TI  - Endolymphatic hydrops associated with otosclerosis.
AB  - Endolymphatic hydrops (EH) associated with otosclerosis has been noted for many
      years. However, the causal relationship of these two entities remains
      controversial. Having reviewed the records of patients with otosclerosis
      describing fluctuant hearing loss and vertiginous symptoms, the authors found the
      EH may coexist with otosclerosis preoperatively; they may be two separate
      diseases that exist coincidentally; or EH may be caused by the otosclerotic
      process. Secondly, EH may occur with a fistula after surgery. Occurring after
      stapedectomy, EH may be caused by fistulization of the bony labyrinth, which is
      effectively treated by surgery to seal the fistula, which may cause EH to subside
      and hearing to improve. Thirdly, delayed EH may occur months or years after
      stapedectomy, possibly as a result of otosclerotic foci or surgical insult to the
      labyrinth. Dexamethasone, diuretics, and a room air rebreather can be used in the
      treatment of delayed EH. Hearing may be maintained or may deteriorate, but there
      usually is no dizziness. The clinical manifestations of EH associated with
      otosclerosis include a conductive or mixed type of hearing loss; the presence of
      fullness, tinnitus, fluctuation of hearing, episodic vertigo, an elevated
      negative summating potential (SP), and an increased summating potential:action
      potential (SP:AP) ratio shown by ECoG. This report presents five cases of EH
      associated with otosclerosis.

PMID- 8579138
TI  - Dynamic visual acuity: a test for oscillopsia and vestibulo-ocular reflex
      function.
AB  - A method has been developed of clinically quantifying dynamic visual acuity
      (DVA), the acuity during imposed head motion in the pitch axis. In this method,
      visual acuity is measured using a computer-controlled projection system during
      vertical, sinusoidal relative motion either of the optotypes (the letters to be
      read) or of a servodriven swinging chair in which subjects are seated. In normal
      persons, the vestibulo-ocular reflex (VOR) functions adequately during imposed
      head movements to limit retinal image instability, making DVA independent of head
      velocity. During head movements the wearing of telescopic spectacles, which
      magnify the visual effects, can overwhelm even normal visual-vestibular
      interactions, producing retinal image instability leading to creation of
      artificial experimental oscillopsia in normal subjects. With the head stationary,
      optotype motion at frequencies and velocities beyond the capabilities of visual
      tracking also results in retinal image motion. Using these methods, DVA for both
      optotype and head motion was found to be degraded in a predictable fashion when
      the velocity of the image on the retina exceeded 2 degrees per second. In two
      patients with total peripheral vestibular loss, DVA was markedly impaired during
      head motion. As a result of the VOR deficit, this impairment of DVA was observed,
      even without the use of telescopic spectacles, and was predictably related to the
      velocity of imposed head motion. Dynamic visual acuity during imposed head motion
      is a quantitative and clinically feasible measure of oscillopsia that reflects
      functionally significant abnormalities of the VOR.

PMID- 8579140
TI  - Management of the small acoustic neuroma: a decision analysis.
AB  - Imaging techniques such as magnetic resonance imaging (MRI) with gadolinium may
      detect small acoustic neuromas before significant symptoms have developed. In
      this situation, the patient and surgeon may question whether the tumor requires
      treatment, especially if the tumor was discovered incidentally. A computerized
      clinical decision analysis was undertaken to model the decision to observe such
      tumors or proceed to immediate surgery. The decision tree was constructed with
      flexibility to account for tumor size, hearing level, and other critical
      variables such as the individual's aversion to unilateral hearing loss and facial
      paralysis. Unless life expectancy is short, the analysis suggests that surgery at
      the time of diagnosis is appropriate, assuming that growth of the tumor is
      anticipated. Variations in surgical proficiency and patient risk aversion within
      expected ranges do not influence the decision to operate. The most critical
      variable appears to be the probability that the tumor will remain stable in size.
      This finding suggests that better data regarding the growth rate of small
      acoustic neuromas is needed.

PMID- 8579141
TI  - Surgical perspectives of endoscopy of the cerebellopontine angle.
AB  - Owing to distal light and panoramic view, the endoscope expands the view inside
      the cerebellopontine angle without touching the cerebellum or the brain stem and
      allows clear identification of the vascular and nervous components crossing the
      cerebellopontine angle. Using a retrosigmoid approach with a combined surgical
      and endoscopic procedure, the surgeon gets more accurate information to visualize
      the adjacent structures to a small acoustic neuroma, to check the lateral part of
      the internal auditory canal, and to locate a vasculonervous cross-conflict. In
      the future, an endoscopic vestibular neurotomy or an endoscopic microvascular
      decompression seems to be a possible approach.

PMID- 8579142
TI  - Malignant hyperthermia in the otology patient: the UCLA experience.
AB  - Malignant hyperthermia is a seemingly rare genetic myopathy. Hypermetabolic
      crisis accompanied by a rise in body temperature to as high as 44 degrees C is
      its hallmark. Malignant hyperthermia is usually triggered by potent inhalational
      anesthetics and/or depolarizing muscle relaxants. Because of the extraordinary
      risk of death in patients who are at risk, otologists may be reluctant to operate
      on these patients. Seven such patients were referred to the Section of Otology,
      Neurotology, and Skull Base Surgery and the UCLA Malignant Hyperthermia Center
      Following first episodes of malignant hyperthermia or with a strong family
      history of malignant hyperthermia for anesthetic and surgical management. They
      were anesthetized with nitrous oxide, barbiturates, opiates, tranquilizers, and
      nondepolarizing muscle relaxants. The patients were not treated prophylactically
      with dantrolene. Cardiac monitoring, end-tidal PC02, and rectal temperatures were
      followed. All seven patients had a vastus lateralis muscle biopsy performed and
      subsequent caffeine/halothane contracture studies completed. The contracture
      study was positive in six of the seven patients studied. No anesthetic or
      surgical complications were encountered. This study demonstrates that patients at
      risk of developing malignant hyperthermia crisis can have otologic surgical
      procedures performed safely while undergoing appropriately selected general
      anesthesia.

PMID- 8579143
TI  - Electrocochleography in profoundly deaf children: comparison of promontory and
      round window techniques.
AB  - It is important to be able to accurately assess residual cochlear function in
      profoundly deaf children. Profound hearing loss in children requires special
      consideration, because the choice between a cochlear implant and a hearing aid
      depends on accurate estimation of the residual hearing. Previous reports confirm
      that promontory (needle) electrocochleography (ECochG) is useful for evaluation
      of residual hearing in severely deaf children, but there were some limitations in
      assessing the lower audiometric frequencies and for assessing profound hearing
      loss. It is argued that accurate placement of a round window electrode (RW
      ECochG) provides better recordings. Round window ECochG testing is performed
      under general anesthesia in young children and gives an opportunity for
      inspection of the middle ear using an endoscope. This report describes a special
      "golf club" electrode that can be placed under direct vision into the round
      window niche, minimizing the risks of damaging an abnormal round window while
      providing the optimum extracochlear recordings. Round window ECochG gives better
      responses, especially in lower audiometric frequencies, than conventional
      promontory ECochG. In the Sydney children's cochlear implant program, RW ECochG
      has become an essential preoperative test.

PMID- 8579144
TI  - Correlation of vascular morphology with clinical types in cholesteatoma of the
      middle ear.
AB  - Cholesteatoma is characterized by the presence of hyperproliferative keratinizing
      squamous epithelium in the middle ear cavity. The abundance and morphology of
      blood vessels in the stroma of cholesteatoma was investigated using a monoclonal
      antibody against an endothelial cell marker, factor VIII-related antigen. Normal
      skin sections were stained for comparison. In cholesteatoma tissue blood vessels
      frequently were more numerous and smaller in caliber than in normal skin. The
      pattern of vascularization differed between the pearly and the dendritic type of
      cholesteatoma. In the dendritic type capillaries with uniform diameter prevailed,
      whereas the pearly type showed blood vessels of variable caliber with a clearly
      visible lumen. This hypervascularization observed in cholesteatoma may be induced
      by factors released from infiltrating immune cells and the squamous epithelium
      and could play an important role in sustaining the continuous abnormal growth of
      the cholesteatoma.

PMID- 8579145
TI  - Argon laser revision stapedectomy.
AB  - This report presents the results of 32 patients who underwent argon laser
      revision stapedectomy. Although the theoretic safety of the argon laser in
      revision stapedectomy has been questioned in the literature, these clinical
      results using this laser are significantly better than those reported using
      mechanical techniques and are comparable to those reported using the CO2 laser.
      Revision stapedectomy using an argon laser delivered to the operative site with a
      fiberoptic handpiece has proved to be a safe and effective technique.

PMID- 8579146
TI  - Density of marginal cell basolateral membranes in basal, middle, and apical turns
      of the rat cochlea.
AB  - The Na-K-ATPase activity within stria vascularis tissues has been observed to
      decrease from basal to apical cochlear turns. This reduction in Na-K-ATPase
      activity in more apical regions of the cochlea may be accounted for, at least in
      part, by a lower density of Na-K-ATPase-containing basolateral membranes of the
      marginal cells. This study was performed to compare the surface density of
      marginal cell basolateral membranes in standardized basal, middle, and apical
      turns of the rat cochlea. Montages of transmission electron microscopic
      micrographs of standardized regions of the rat stria vascularis were
      morphometrically analyzed. Surface area of marginal cell basolateral membrane was
      determined per unit stria vascularis volume and per unit marginal cell volume.
      Results demonstrated that the surface density of marginal cell basolateral
      membrane per stria vascularis volume of the standardized basal region increased
      20 percent compared to that of the standardized apical region (p < or = .1).
      Surface density of marginal cell basolateral membranes per marginal cell volume
      was similar in all three standardized turns. The observed longitudinal
      differences in surface density of marginal cell basolateral membranes per stria
      vascularis volume may account, in part, for the biochemical cochlear Na-K-ATPase
      activity gradient from base to apex.

PMID- 8579147
TI  - Facial nerve stimulation produced by cochlear implants in patients with cochlear
      otosclerosis.
AB  - Thirty-eight adult cochlear implants have been performed at the University of
      Minnesota. Facial nerve stimulation by the implant in response to sound has been
      noted in four of these cases. Three of the four were patients whose sensorineural
      hearing loss was caused by cochlear otosclerosis. In each case it was possible to
      place the electrodes, however multiple leads had to be deprogrammed in order to
      avoid facial nerve stimulation. In each case characteristic radiographic findings
      of cochlear otosclerosis could be identified on preoperative temporal bone
      computed tomography scans. Although facial nerve stimulation has been described
      as a complication of cochlear implantation, it has not been reported to be
      associated with cochlear otosclerosis. Postoperative programming of the implant
      may be limited by facial nerve stimulation. In some cases these limits may reduce
      the efficacy of the device. This possibility should be taken into account during
      preoperative counseling of patients with cochlear otosclerosis considering
      cochlear implantation.

PMID- 8579148
TI  - Vestibular dysfunction in a child with embryonic exposure to accutane.
AB  - Children with a history of embryonic exposure to Accutane (isotretinoin) are at
      great risk for major physical malformations, brain malformations, and decreased
      intelligence. A case is presented of a 4-year 7-month-old black male with a
      history of embryonic exposure to Accutane who was born with embryopathy that
      includes bilateral major ear deformities. The child has a significant bilateral
      conductive hearing loss, and, in addition, a left sided sensorineural loss.
      Vestibular function testing revealed evidence of peripheral and central
      vestibular dysfunction. A course of diphenhydramine hydrochloride and Donnatal
      (phenobarbital, hyoscyamine sulfate, atropine sulfate, and scopolamine
      hydrobromide) significantly alleviated the symptoms of vestibular dysfunction.
      Otologic management of these children should include clinical documentation of
      the external deformities, evaluation of cochlear function, and early auditory
      habilitation. Vestibular function should also be evaluated in all children with a
      history of embryonic exposure to isotretinoin.

PMID- 8579149
TI  - Objective tinnitus in patients with atherosclerotic carotid artery disease.
AB  - Atherosclerotic carotid artery disease (ACAD) as a cause of objective-pulsatile
      tinnitus has not been adequately addressed in the literature. This report
      presents the authors' experience in 12 patients with pulsatile tinnitus arising
      from ACAD. Ipsilateral carotid bruit was detected in all patients and objective
      tinnitus was present in eight cases. The intensity of the carotid bruit was
      louder than the objective tinnitus in all patients. Carotid artery stenosis was
      confirmed in all patients with noninvasive vascular flow mapping. Atherosclerotic
      carotid artery disease should be highly suspected in patients with pulsatile
      objective tinnitus who are older than 50 years and have associated cardiovascular
      risk factors. Pulsatile tinnitus in these patients can be the first manifestation
      of ACAD. Duplex ultrasound study of the carotid arteries can confirm the
      diagnosis. Consultation with a vascular surgeon is essential in selected cases.

PMID- 8579150
TI  - Otitis externa: management of the recalcitrant case.
AB  - Most cases of otitis externa respond to routine treatment, however, there is a
      subset of patients who frequently develop otitis externa that is usually severe
      and recalcitrant to routine therapy. These patients include the
      immunocompromised, those with AIDS, transplant recipients, severe diabetics,
      patients treated with high dose steroids or chemotherapeutic agents, and those
      who are malnourished or are chronically ill. Local factors that lead to worsening
      of otitis externa include dermatitides and prior local irradiation. Patients who
      find topical therapy painful may be noncompliant with medications, and they too,
      may develop recalcitrant otitis externa. For successful treatment, a broad
      understanding of external auditory canal anatomy, the microbiology and
      pathophysiology of otitis externa, and available treatment options, including
      topical and systemic medications, must be attained. These topics are reviewed.

PMID- 8579151
TI  - Facial paralysis secondary to tympanic mucormycosis: case report.
AB  - Mucormycosis is a saprophytic fungal disease. In the region of the head, it has
      been recognized to invade nasal cavity, paranasal sinus, orbit, or intracranial
      structures. However, unique involvement of the middle ear, with facial paralysis,
      still remains unreported. An unusual experience with a diabetic who developed
      this disease is described. Surgical debridement and amphotericin B administration
      resulted in near-total cure. The significance of this report is to add a new site
      involved by mucormycosis, that is, the tympanic cavity.

PMID- 8579152
TI  - Superficial siderosis of the central nervous system: an underdiagnosed cause of
      sensorineural hearing loss and ataxia.
AB  - Superficial siderosis of the central nervous system (CNS) is a rare but
      ultimately fatal disorder characterized by progressive hearing loss, ataxia, and
      dementia. Symptoms are caused by the deposition of hemosiderin in the CNS as a
      result of recurrent or persistent extravasation of blood into the cerebrospinal
      fluid. Sites most commonly involved include the cerebellum, brain stem, and
      eighth cranial nerve. In the past, diagnosis was most often made at autopsy, and
      this may account for the lack of reported cases in the otolaryngologic literature
      and the presumed rarity of the disorder. Now, diagnosis is confirmed by
      characteristic magnetic resonance imaging findings and treatment is targeted
      toward the source of bleeding. The diagnosis of superficial CNS siderosis should
      be entertained in all patients presenting with sensorineural hearing loss and
      ataxia.

PMID- 8579154
TI  - Sudden deafness from vertebrobasilar artery disorder.
AB  - Two cases are presented of sudden deafness with vertigo and/or dizziness, a 19
      year-old male and a 54-year-old female. Their onset condition was considered to
      be caused by vascular disorders in the area of the vertebrobasilar artery, but
      they showed no signs of the central nervous system disorders. Case 1 suffered
      right sudden deafness just after a super selective embolization for the
      peripheral area of the right vertebral artery, and case 2, just after the
      accidental cutting of the left vertebral artery during the procedure of
      neurovascular decompression surgery. The neurotologic findings in these cases
      were almost the same and the common characteristics were (1) irreversible total
      deafness of the affected ear, (2) canal paresis in caloric test, (3)
      retrolabyrinthine disorder of the vestibular system detected by the galvanic
      test, and (4) no obvious findings of central nervous system disorders, such as
      eye movement disorder or ataxy. These findings indicate that the sudden deafness
      was attributable to localized embolism in the inner ear artery caused by
      thrombosis in the area of the vertebrobasilar artery.

PMID- 8579153
TI  - Low-grade myxoid chondrosarcoma of the temporal bone: differential diagnosis and
      report of two cases.
AB  - Skull base chondrosarcoma and chordoma are rare tumors that generally have a poor
      prognosis. In 1973, Heffelfinger et al described a chondroid variant of chordoma,
      called chondroid chordoma that was found to have a significantly better prognosis
      than classic chordoma. However, recent evidence suggests that many of the tumors
      diagnosed as chondroid chordoma may, in fact, be low-grade myxoid
      chondrosarcomas. This report presents the diagnosis and treatment of two cases of
      skull base tumor that were diagnosed preoperatively as schwannoma because they
      were thought initially to be centred on the jugular foramen. Initial histologic
      evaluation suggested chondroid chordoma, but immunohistologic techniques and a
      review of the literature led to a diagnosis of low-grade myxoid chondrosarcoma.

PMID- 8579155
TI  - Simultaneous presentation of facial nerve neuroma and otosclerosis.
AB  - Otosclerosis often occurs as a unilateral mixed or conductive hearing loss. In
      the absence of retrocochlear findings, otologists usually do not pursue further
      diagnostic testing. A patient who presented to the Warren Otologic Group with a
      unilateral mixed hearing loss is discussed. He was followed for 1 year with the
      intent of scheduling a stapedectomy. Two weeks prior to the surgical date, the
      patient developed a sudden hearing loss and was admitted to the hospital for
      treatment. Magnetic resonance imaging demonstrated a tiny, enhancing mass in the
      lateral internal auditory canal, measuring 7 mm in diameter. At surgery, the
      tumor was found to originate at the union of the nervus intermedius and the
      facial nerve. The simultaneous occurrence of facial nerve neuroma and
      otosclerosis is discussed, with emphasis on a thorough evaluation of all
      unilateral mixed hearing losses, including those attributable to otosclerosis.

PMID- 8579156
TI  - Hearing loss and the Mayer-Rokitansky-Kuster-Hauser syndrome.
AB  - The hearing of 51 female patients with the Mayer-Rokitansky-Kuster-Hauser
      syndrome was examined using otoscopy and standard audiometry. A unilateral or
      bilateral hearing loss of more than 15 dB Fletcher index was found in 13 of 51
      (25.5%). Four of these 13 patients had a hearing loss of less than 20 dB in the
      worst ear. The remainder had a hearing loss of at least 30 dB in the worst ear.
      Five of the 13 patients had pure conductive hearing loss; in four of these five,
      a congenital origin was accepted. Two of the 13 had mixed hearing loss that was a
      residual symptom from previous otitis media; six had sensorineural hearing loss.
      A congenital cause was found in one of these six, based on the fact that she had
      been deaf and dumb since birth. In one other patient, noise-related deafness was
      likely (i.e., an acquired cause). In the other four cases in this group, the
      cause was unknown. The results of this study show that hearing loss is a
      characteristic associated with the Mayer-Rokitansky-Kuster-Hauser syndrome.

PMID- 8579157
TI  - Extensive facial nerve tumor with atypical histology: case report.
AB  - Primary facial nerve tumours are uncommon; most are benign schwannomas. Rare
      cases of malignant schwannomas and cellular schwannomas have been reported. The
      report describes a multicentric facial nerve tumor that did not fit well into any
      of these histopathologic categories. The tumor was removed in two stages and the
      patient has no clinical or radiographic evidence of recurrence 2 years after the
      initial procedure.

PMID- 8579158
TI  - Neuroma of the facial nerve masked by chronic otitis media.
AB  - The absence of facial twitching, weakness, or palsy makes the diagnosis of facial
      neuroma difficult. The authors report a case of neuroma of the horizontal portion
      of the facial nerve masked by the presence of a chronic ear. A woman with a long
      history of discharge and hypoacousia in her left ear presented with acute
      dizziness. Examination revealed grade 3 horizontal right nystagmus, left
      anacousia, and the appearance of an epitympanic cholesteatoma. Computed
      tomography (CT) was performed after the vestibular condition improved. The
      clinical diagnosis of chronic otitis media with cholesteatoma together with the
      radiologic finding of the mastoid and tympanic cavity completely occupied by soft
      tissue were enough to send the radiologist astray. The radiologic diagnosis
      confirmed that the bony destruction of the vestibule and lateral semicircular
      canal could be caused by a cholesteatoma. A neuroma of the horizontal portion of
      the facial nerve was discovered during surgery performed for the chronic ear. The
      postoperative study of the CT scans showed that there was no erosion of the
      malleus or incus, despite wide erosion of the vestibule and lateral semicircular
      canal. This finding would be enough to suggest the presence of pathology other
      than cholesteatoma. The patient refused exeresis of the neuroma. The authors
      recognize the difficulty in urging a patient to an operation that surely will
      result in worsening of the facial function. Follow-up in this case has revealed
      no change in tumor dimension or facial function over 3 years.

PMID- 8579159
TI  - Myringochorda-vestibulopexy: a new method for total replacement of the ossicular
      chain.
AB  - A new method is described for total replacement of the ossicular chain if the
      ossicles are absent and malleovestibulopexy does not form a solution. One end of
      a 0.4-mm thick Teflon-platinum piston was fixed to the chorda tympani, and the
      other end was inserted into an opening made during stapedotomy. Contact between
      the piston and tympanic membrane was achieved by placing autologous cartilage
      between the posterior upper quadrant of the tympanic membrane and the chorda. The
      results of a second patient at 2-year follow-up are presented.

PMID- 8579160
TI  - Recurrent facial palsy: diagnostic and therapeutic challenge.

PMID- 8579161
TI  - Simultaneous bilateral facial paralysis and abnormal ABR: differential diagnosis
      and management.

PMID- 8579162
TI  - Simultaneous bilateral facial palsy with an abnormal stapes reflex.

PMID- 8579163
TI  - Permanent middle ear aeration.

PMID- 8579164
TI  - Current challenges in management of cranial base meningiomas.

PMID- 8579165
TI  - Intracranial complications of suppurative otitis media: 13 years' experience.
AB  - Among 24,321 patients with otitis media treated at the Otolaryngology Department
      of Chiang Mai University Hospital from 1978 through 1990, 87 patients had 140
      central nervous system complications (0.36%). Multiple complications existed
      simultaneously in almost 45% of the patients. The group developing the
      complications were mainly in their second decade of life. Meningitis occurred in
      43 patients, brain abscess in 29, perisinus abscess in 23, lateral sinus
      thrombosis in 16, and extradural abscess in 12 patients. The most striking
      symptoms and signs were increasing otorrhea, visible cholesteatoma and/or
      granulations, fever, headache and otalgia, and vestibular symptoms. Proteus
      mirabilis, Pseudomonas aeruginosa, and staphylococcal organisms were found in
      almost 80% of patients. Overall mortality was 18.4% with brain abscess being the
      main cause (31%). Epidemiologic presentation, clinical features, and results of
      treatment for each disease are compared and contrasted to those of previous
      studies.

PMID- 8579166
TI  - Labyrinthectomy in the elderly.
AB  - This study involved elderly patients with Meniere's disease with incapacitating
      vertigo. Several of these patients underwent surgery for relief of symptoms that
      was tailored to the individual's general health and degree of physical activity.
      Factors that might affect postoperative rehabilitation and recovery were
      considered, including vision, vertebrobasilar ischemia, proprioception (such as
      neuropathy resulting from diabetes), and basal ganglia disease. The postoperative
      results of this tailored approach have been completely satisfactory.

PMID- 8579167
TI  - Intraoperative neurophysiologic monitoring.

PMID- 8579168
TI  - Cochlear implants: it's time to rethink.

PMID- 8579169
TI  - Cochlear implants: it's time to rethink.

PMID- 8579170
TI  - Cochlear implants: it's time to rethink.

PMID- 8579171
TI  - Cochlear implants: it's time to rethink.

PMID- 8579172
TI  - Characterization of DNA extracted from archival celloidin-embedded human temporal
      bone sections.
AB  - The focus of the present investigation was to study, via molecular biology
      techniques, the character of the DNA present in individual archival celloidin
      embedded human temporal bone sections. Polymerase chain reaction (PCR)
      amplification of 92 base pair (bp), 121 bp, and 471 bp regions of mitochondrial
      DNA (mtDNA) extracted from a single archival celloidin-embedded human temporal
      bone section was used to assess the length of the template DNA extracted. The
      effects of digestion time and sample motion during the extraction method on DNA
      concentration was also studied. These data are crucial to determine the limits of
      applying PCR technology to amplify specific genomic DNA targets located within
      the human inner ear. Further development of these methods will allow additional
      molecular temporal bone pathologic studies to be completed and, more
      specifically, hypotheses regarding the molecular etiopathogenesis of many
      auditory, vestibular, and facial nerve disorders, such as autoimmune hearing
      loss, congenital hearing losses, Meniere's disease, otosclerosis, or Bell's palsy
      could be tested. The results described should be of great value to those
      investigators extracting DNA from archival individual human temporal bone
      sections for PCR assays of specific genetic alterations or infectious agents
      associated with temporal bone pathologies.

PMID- 8579173
TI  - Composite autograft "shield" reconstruction of remnant tympanic membranes.
AB  - The authors present their combined experience with large cartilage-perichondrial
      composite grafts used to reconstruct total tympanic membrane perforations in 294
      ears. Patients chosen for this procedure had failed earlier tympanoplasty surgery
      or were identified as poor candidates for conventional facial tympanoplasty
      because of the perforation size. Successful perforation closure was achieved in
      97% of ears with chronic otitis media characterized by absence of the tympanic
      membrane, including portions of the anterior annular ligament. Hearing results in
      general were good, considering the advanced stage of the disease, which required
      the use of alloplastic ossicular prostheses (PORP and TORP) in 76% of ears.
      Hearing improvement was maximal at 2000 Hz regardless of the method of ossicular
      reconstruction. Closure of the air-bone gap at this frequency to within 10 dB was
      achieved in 87% of type I tympanoplasties, 73% of type III (PORP), and 70% of
      type III (TORP) tympanoplasties. Although cartilage autografts have also been
      promoted to reverse tympanic membrane atelectasis, the authors believe that the
      above preoperative conditions are strong indications for this grafting technique,
      which is described in detail.

PMID- 8579174
TI  - Hearing loss in Paget's disease of bone: evidence of auditory nerve integrity.
AB  - Auditory brainstem responses (ABRs) were recorded in 64 ears with
      radiographically confirmed Paget's disease involving the skull. Responses were
      absent in eight ears, all of which had elevated high pure-tone thresholds.
      Auditory brainstem responses were interpreted as normal in 56 ears; none were
      abnormal. Computed tomography and digital image analysis were used to quantify
      internal auditory canal (IAC) dimensions. The midlength diameter and minimum
      diameter of the IAC of 68 temporal bones from subjects with Paget's disease were
      found to have no statistically significant relation to hearing thresholds.
      Increased IAC length showed a limited relation to reduced hearing level in
      pagetic subjects, possibly consistent with bossing adjacent to the porus
      acusticus. Findings support the principle that hearing loss in Paget's disease of
      bone is generally associated with intact auditory nerve function and also support
      a cochlear site of lesion.

PMID- 8579175
TI  - William F. House Lecture. Neurotologic manifestations of microvascular
      hypoperfusion.
AB  - Some forms of dizziness, imbalance, and hearing change have been suspected to
      result from a vertebral basilar artery circulatory deficit. Microvascular
      hypoperfusion of the central nervous system (CNS) is proposed as a more likely
      mechanism than thromboembolic phenomena of the parent arteries. Symptoms of end
      organ pathology must be differentiated from CNS causes to assure implementation
      of an appropriate treatment strategy. Guidelines for the evaluation of these
      patients are provided. Changes in platelet and red and white blood cell
      morphology are proposed as more significantly influencing blood flow than blood
      pressure or vessel caliber. Medications that alter blood rheology, have been
      found to alleviate the acute symptoms of microvascular hypoperfusion. Residual
      balance deficits from presumed long-term CNS ischemia have then been relieved by
      balance rehabilitation training. With the recognition of this disease entity
      there appears another means of aiding patients with dizziness and balance
      problems who have previously experienced long-term disability. The results of a
      preliminary study of 378 patients merits further investigation of the proposed
      pathophysiology and treatment measures.

PMID- 8579176
TI  - Systematic approach to intradural tumors ventral to the brain stem.
AB  - Intradural tumors that are situated anterior to the midbrain, pons, and medulla
      have historically been among the most inaccessible of all intracranial lesions.
      The classic approaches to the posterior fossa (e.g., suboccipital, retrosigmoid)
      provide only limited access to the anterior midline, primarily due to
      interposition of the cerebellum, brain stem, and numerous cranial nerves between
      the tumor and the viewpoint of the surgeon. A variety of techniques have been
      developed in recent years that create a craniotomy by removal of a portion of the
      lateral skull base. These procedures enhance exposure of the ventral surface of
      the brain stem while markedly reducing the need for brain retraction. An
      underlying theme of transbasal craniotomy is judicious removal of a portion of
      the petrous pyramid. The most radical form of petrosectomy, the extended
      transcochlear approach, involves removal of the entire petrous pyramid along with
      the lateral aspect of the clivus. This provides an unimpeded view of the ventral
      surface of the pons, including the basilar artery, vertebrobasilar junction, and
      both abducens nerves. Whereas this technique provides splendid exposure along the
      midsegment of the brain stem, it carries substantial morbidity, including hearing
      loss and transient facial palsy, which typically recovers incompletely and with
      synkinesis. Over the past few years transcochlear procedures have been gradually
      supplanted, at the University of California Medical Center, by techniques that
      involve creating a simultaneous craniotomy of both the middle and posterior
      fossae fashioned around a more limited petrosectomy. These versatile procedures,
      in particular the middle fossa/retrolabyrinthine approach, provide excellent
      exposure of the region ventral to the midbrain and pons with less morbidity than
      the transcochlear approach. When tumors extend inferiorly, ventral to the lower
      medulla and/or upper cervical spinal cord, augmented inferior exposure is
      required. Approaches to ventrally situated lesions at the craniovertebral
      junction include the far lateral (transcondylar) approach to the foramen magnum
      and the transjugular approach, both of which involve removal of the inferior
      portion of the petrous bone. To efficiently utilize these innovative surgical
      options the surgeon must decide which of the potential approaches optimizes
      resection while minimizing morbidity. An analysis of the anatomy of the tumor,
      the functional integrity of cranial nerves, and the extent of resection planned
      provides the surgeon with the information needed to arrive at a rational choice.

PMID- 8579177
TI  - Review of the formative years--a guide for the future.

PMID- 8579178
TI  - Cost effectiveness of the multichannel cochlear implant.
AB  - Although most third-party payors presently fund cochlear implantation, some do
      not, and many cite the current lack of cost-effectiveness data as a major
      concern. Cost-utility analysis is a widely used method of medical technology
      assessment that permits cost-effectiveness comparisons between medical
      interventions by determining the cost per quality-adjusted life-year (QALY) they
      provide. The cost per QALY for the cochlear implant was determined using clinical
      cost data and a health-utility outcome model based on the established
      communication gains attained with the device. Cochlear implantation costs
      approximately $15,600 per QALY provided. Sensitivity analysis, a technique that
      systematically varies the assumptions underlying the calculations, favorably with
      other medical interventions, such as coronary artery bypass grafting ($10,431)
      for three-vessel disease, $64,033 for single-vessel disease), the implantable
      defibrillator ($29,200), and cardiac transplantation ($38,970). This analysis
      indicates that the cochlear implant lies well within the cost-effectiveness range
      currently accepted by the American medical system.

PMID- 8579179
TI  - Utility of auditory brainstem response audiometry in diagnosis of acoustic
      neuromas.
AB  - Auditory brainstem response (ABR) audiometry is said to be 90% sensitive in the
      diagnosis of acoustic neuromas. Since gadolinium-DTPA was introduced, magnetic
      resonance imaging (MRI) is capable of detecting acoustic neuromas as small as 3
      mm. Early diagnosis is important, because hearing can frequently be preserved
      with resection of tumors smaller than 2 cm. At the same time, cost-containment
      has become a pressing issue in medicine. Auditory brainstem response, although
      considerably less expensive than MRI, may not be as sensitive as previously
      thought, particularly for small tumors. Of 753 acoustic neuromas treated at the
      House Ear Clinic from January 1988 through March 1993, 197 had ABR data
      available. The 98 males and 99 females ranged in age from 13 to 78 years with a
      mean of 48 years. The overall sensitivity of ABR was 92.3% using an interaural
      latency difference for wave V of more than 0.2 ms, and was 81.6% using waveform
      morphology. There was a statistically significant difference in sensitivity with
      respect to tumor size. Auditory brainstem response interaural latency difference
      sensitivity ranged from 100% in tumors larger than 3.0 cm to 83.1% in tumors 1.0
      cm or smaller. Waveform morphology was abnormal in 100% of tumors larger than 2.0
      cm but in only 76.5% of tumors 1.0 cm or smaller.

PMID- 8579180
TI  - Magnetic resonance imaging and intraoperative frozen sections in intratemporal
      facial schwannomas.
AB  - Seven cases of intratemporal facial schwannoma were assessed by preoperative
      magnetic resonance imaging (MRI) and intraoperative frozen sections to determine
      tumor boundaries. These results were then analyzed with respect to gross tumor
      appearance, under the operating microscope, and final histopathologic diagnosis,
      with immunostains. Gadolinium-enhanced MRI was helpful in planning the surgical
      and approach and in defining the extent of tumor involvement relative to the
      facial nerve. Frozen sections on the other hand were often unreliable in
      confirming the completeness of resection, frequently overestimating tumor
      infiltration. Ultimately, tumor-nerve interface, especially in the proximal
      facial segments, is best judged by its gross intraoperative appearance under high
      magnification, with the aid of MRI. The difficulty in establishing tumor
      infiltration in the presence of organized neutral fibers and artifacts is
      emphasized. Immunohistochemical assays are essential in this regard. Complete
      tumor removal was achieved in all seven cases, with acceptable functional outcome
      in those with sufficiently long follow-up.

PMID- 8579181
TI  - Changes in goblet cell density in rat middle ear mucosa in acute otitis media.
AB  - This study was undertaken to determine quantitative histologic changes after a
      single episode of acute suppurative otitis media in the rat middle ear mucosa,
      with special reference to goblet cell density, and to determine the persistency
      of these changes. Drum vascularization, purulent effusion, mucosal thickness,
      bone and subepithelial gland formation was assessed. Twenty-five rats were
      inoculated with viable pneumococci type 3 through the right, bony middle ear
      bulla. The left bulla served as control. At days 4, 8, 16, 90, and 180 after
      inoculation, five rats were sacrificed on each occasion; the bullae were removed,
      opened, and divided into two halves, which were stained according to the periodic
      acid-Schiff (PAS)-alcian blue method. The stained mucosa was dissected from the
      bone and placed in an anise oil-colophonium chamber, for determination of
      interindividual median density and range of goblet cells by light microscopy.
      Counting was performed in 24 well-defined localities, covering the entire bulla
      mucosa and the drum. Areas normally containing goblet cells were extended. Goblet
      cell density was significantly (Mann-Whitney, p < .05) increased in almost all
      localities, reaching a maximum at day 16, whereafter the mucosa normalized. All
      changes quantitated, except drum vascularization and purulent effusion, were
      persisting at day 180. Cobblestone appearance of the epithelial surface and
      polypous mucosal prominences were found. Mucosal thickening was prominent in
      areas covered with flat epithelium, less so in other areas. Local differences in
      the degree of increased mucosal thickness were preventing intrinsic tubal
      occlusion. Enhanced secretory ability of the middle ear mucosa was persisting 6
      months after a single episode of acute suppurative otitis media, perhaps
      predisposing secretory otitis media.

PMID- 8579182
TI  - Comparison of multichannel tactile aids and multichannel cochlear implants in
      children with profound hearing impairments.
AB  - Speech perception skills of prelingually deafened children who used the
      multichannel Tactaid 7 (n = 10) were compared to those of a matched group of
      children who used the Nucleus 22 channel cochlear implant (n = 10). Group scores
      were compared on a closed-set test of word recognition and on an open-set test of
      phrase recognition in the pre-device condition and at a post-device interval
      after an average of 1.5 years of multichannel device use. The results revealed
      that the scores of the implant users improved significantly between the pre- and
      post-device intervals on all measures. Moreover, the scores of the implant users
      were significantly higher than those of the tactile aid users on all measures. In
      contrast, the scores of the tactile aid users showed negligible change over time,
      except on a test that evaluated open-set recognition of phrases with both
      auditory and visual cues. The results suggest that children can learn to
      recognize words and understand speech without lipreading with a multichannel
      implant, whereas children who used the multichannel tactile aid demonstrate
      limited speech recognition skills only if auditory/tactile cues are combined with
      lipreading.

PMID- 8579183
TI  - Non-osteitic complications of therapeutic radiation to the temporal bone.
AB  - The temporal bone often falls within the field of radiation for head and neck
      tumors. Whereas osteoradionecrosis is well recognized as the end-stage
      complication of radiation to the temporal bone, serious non-osteitic
      complications can also occur, and these are important because the ear is an organ
      of special sense. Radiation causes changes in the specialized tissues of the ear
      that can impair function and influence therapeutic decisions. The purpose of this
      article is to review the non-osteitic effects of radiation on the ear. A series
      of cases is presented that illustrate the spectrum of non-osteitic complications
      of radiation therapy. External canal stenosis, otitis media with effusion,
      chronic suppurative otitis media with or without cholesteatoma, sensorineural
      hearing loss, vestibular impairment, and facial nerve paralysis are described.
      Management should be guided by an understanding of the pathogenesis of these
      complications. The authors believe that non-osteitic complications of therapeutic
      radiation to the temporal bone are relatively common and warrant increased
      recognition.

PMID- 8579184
TI  - Abnormalities in posturography and estimations of visual vertical and horizontal
      in multiple sclerosis.
AB  - Twenty-seven patients with mild multiple sclerosis were tested with the dynamic
      posturography protocol used in the NeuroCom Equitest procedure. The purpose of
      this study was to determine if the standard test procedure elicited a pattern of
      responses that would suggest the possibility of multiple sclerosis during
      differential diagnosis of a patient with dysequilibrium. In addition, the
      patients' ability to align a light bar to vertical and horizontal was tested with
      the head erect and with the head tilted 45 degrees to the right and left
      shoulder. There was a pattern of abnormality in the Equitest motor coordination
      tests. Only one patient produced normal scores in both the latency and adaptation
      tests. No pattern of error was noted in the sensory organization tests. In the
      visual alignment tests, only 3 of the 27 patients tested produced values that
      were within normal limits for the three different head positions. Visual
      alignment and the motor coordination tests are not specific for multiple
      sclerosis, but poor performance probably indicates a disruption of the
      integration of visual, vestibular, and somatosensory information. Although
      patients with early multiple sclerosis and patients with purely vestibular
      disorders often have similar complaints, they have quite different profiles of
      abnormalities in posturography testing.

PMID- 8579185
TI  - Non-paraganglioma jugular foramen lesions masquerading as glomus jugulare tumors.
AB  - Pulsatile tinnitus, hearing loss, lower cranial nerve deficits, and radiographic
      evidence of a vascular lesion of the jugular foramen have been considered
      diagnostic of a glomus jugulare tumor. Angiographic evidence of a blood supply
      from the external carotid artery system, including the ascending pharyngeal
      artery, further substantiates this diagnosis. This diagnostic algorithm for
      tumors of the jugular fossa is usually followed by either a surgical exenteration
      of a presumed glomus jugulare tumor via an infratemporal fossa approach or
      radiation therapy in selected patients. Pre-treatment biopsy of such lesions is
      typically not done, nor is it recommended widely in the literature. As
      demonstrated in this report, a number of lesions, including hemangiopericytoma
      and extramedullary plasmacytoma presenting in the jugular foramen can mimic
      glomus jugulare tumors in all aspects of their clinical and radiographic
      presentation. Omission of a pre-treatment biopsy can lead to a treatment plan
      appropriate for glomus tumors but suboptimal for these rare pathologic entities.
      A pre-treatment biopsy of lesions of the jugular foramen by exploratory
      tympanotomy or postauricular mastoidotomy provides a pathologic diagnosis on
      which to base treatment of lesions of the jugular foramen, without adding
      substantial morbidity or decreasing the chances of cure.

PMID- 8579186
TI  - Evaluation of mastoid obliteration surgery.
AB  - The anatomic results of mastoid obliteration surgery on 54 ears during the past
      10 years were analyzed, and the comparative utility of several materials for
      obliteration was evaluated. Thirty-three ears had primary chronic otitis media
      with or without cholesteatoma (group 1), and 21 ears had old open mastoid with
      intractable chronic discharge due to incomplete epithelialization (group 2). The
      materials used for obliteration were biologic (pedicled muscle flap, autogenous
      bone chips, tragal cartilage with perichondrium, allograft dura), nonbiologic
      (hydroxyapatite), or a combination of two of these materials. Evaluation at 2
      months postoperatively showed that 42 ears were anatomically complete, whereas
      the other 12 ears were incomplete: three cases in group 1 and nine cases in group
      2. The main causes of these unsatisfactory results were exposure of transplanted
      artificial material or partial loss of the pedicled muscle flap. In the long-term
      follow-up results, four ears were evaluated as unsatisfactory in group 1, and six
      ears in group 2, owing to shrinkage of obliterated tissue. The major causes of
      failure were anatomic incompleteness following surgery for old open mastoid
      cavity, in which the use of biologic materials for obliteration was much safer
      than nonbiologic material, and from the protrusion of artificial materials used.

PMID- 8579187
TI  - Genetic consequences of differential demographic behaviour in the Saguenay
      region, Quebec.
AB  - Some rare inherited disorders are found with a high frequency in the population
      of the Saguenay region (Quebec province, Canada, population 300,000). Inbreeding
      coefficients are too low to be an explanation for these high frequencies. In the
      first decades of settlement (1842-1870), most of the immigrants came from a small
      region called Charlevoix (east of Quebec city). As most of the genetic disorders
      found in the Saguenay region are also found in the Charlevoix region, it is
      strongly suspected that the genes were introduced by these first settlers from
      Charlevoix. Using the BALSAC database (which contains linked information on the
      entire Saguenay population) to calculate the number of contemporary descendants
      and the genetic contribution of each founder to these descendants, we show that:
      (1) Founders who entered the population before 1870 contribute to 45% of the
      contemporary gene pool, despite the fact that they represent only 15% of all the
      20,012 immigrants with descendants in the contemporary population (individuals
      born between 1950 and 1971). (2) Their genetic contribution is not homogenous in
      the contemporary population: 5% of the population have 100% of their gene pool
      coming from these first founders, while 10% have a zero to 5% contribution from
      these earliest founders. (3) Fifty percent of the genes introduced in the
      population were lost. (4) If only 68 immigrants among the first founders (2.0%)
      were carriers of the same gene, it could reach a frequency of 5% in the
      contemporary population, which is the frequency of most of the inherited
      disorders found in the population.

PMID- 8579188
TI  - New characters for the functional interpretation of primate scapulae and proximal
      humeri.
AB  - The study of muscle function in nonhuman primates through the technique of
      electromyography (EMG) has facilitated the identification of specific functional
      roles for muscles in particular behaviors. This has led to a more complete
      understanding of the biomechanics of certain regions of the musculoskeletal
      system, and should facilitate our ability to identify morphological features
      useful in the functional interpretation of fossil material. The current paper
      represents one such investigation of a new set of morphometric characters of the
      scapula and proximal humerus suggested by EMG analyses of shoulder muscle
      function. A set of new metric variables were examined on the scapulae and
      proximal humeri of 25 species of extant anthropoid primates, as well as on casts
      of scapulae and humeri of three fossil primate taxa. The variables are primarily
      related to the line of action and attachments of the rotator cuff muscles. The
      position of the scapular spine, the degree of lateral expansion of the
      subscapular fossa, the size and shape of the subscapularis insertion facet on the
      lesser tubercle, and the orientation of the infraspinatus insertion facet on the
      greater tubercle all appear to successfully sort the extant taxa into locomotor
      groups. Their appearance on the fossil specimens generally supports previous
      functional interpretations of each taxon's locomotor abilities based on a variety
      of other characters, suggesting that these traits are equally applicable to
      fossil material.

PMID- 8579189
TI  - Pre-Columbian tuberculosis in northern Chile: molecular and skeletal evidence.
AB  - Analysis of 483 skeletons from Arica (Chile) and review of mummy dissection
      records demonstrates an overall 1% prevalence rate for tuberculosis between 2000
      B.C. and A.D. 1500. Tuberculosis cases cluster in the period A.D. 500-1000 which
      correlates with fully agropastoral societies. Considering only these agropastoral
      societies, about 2% of their members show tuberculosis lesions. A segment of DNA
      unique to Mycobacterium tuberculosis was identified in an extract from the
      vertebral lesion of a 12-year-old girl with Pott's disease from about A.D. 1000,
      establishing the pre-Columbian presence of tuberculosis with the most specific
      evidence currently available.

PMID- 8579190
TI  - Growth differences between children of highland and coastal Ecuador.
AB  - This study examines patterns of growth in height and weight among children (< 60
      months) of highland and coastal agricultural communities of Ecuador. Highland
      children are significantly shorter, but not significantly lighter than their
      coastal peers. Linear growth rates (cm/6 months) are comparable between the two
      samples. Growth rates for body weight (kg/6 m) are similar in highland and
      coastal boys, whereas highland girls display larger weight gains than their
      coastal counterparts. In both regions, linear growth is compromised to a much
      greater extent than growth in body weight, and growth faltering for both height
      and weight is most pronounced between birth and 24 months of age. The similarity
      in growth rates between the highland and coastal samples suggests that high
      altitude hypoxia plays a relatively small role in shaping growth during the first
      five years after birth. Rather, it appears that most of the disparity in height
      between the two samples can be attributed to differences established by 6 months
      of age. The pattern of growth retardation seen in both regions during the first
      24 postnatal months is similar to that observed among impoverished populations
      throughout the world and is likely associated with the influence of nutritional
      and disease stressors. After 2 years of age, little or no "catch up" growth is
      seen in height, whereas improvements in weight gain are more pronounced,
      especially among highland girls. Ongoing research is investigating the
      nutritional and socio-economic correlates of growth within each region.

PMID- 8579191
TI  - Natural selection and developmental sexual variation in the human pelvis.
AB  - This research examines ontological patterns of change in variation of the human
      pelvis as a means of identifying regions of differential growth, growth
      canalization and evidence of selection. Data were derived from pelvic
      radiogrammetry of 180 8-year-olds and 89 subjects at age 18 who were part of the
      Fels Longitudinal Growth Study. Coefficients of variation (CVs) and total growth
      increments were compared between sexes and between ages 8 and 18 for 14 pelvic
      measures. Sex-specific comparisons of mean size were tested per age using
      Student's t, whereas coefficients of variation were calculated and compared using
      the methods suggested by Sokal and Braumann ([1980] Syst. Zool. 29:50-66). The
      Mann-Whitney U-test was used to test median growth increments between ages 8 and
      18. Results of these comparisons show significant sex differences in breadth of
      the ischium and acetabular regions among 8-year-olds. Most of the sexual
      dimorphism in the pelvis at age 18, however, develops during the adolescent
      growth period, during which both male and female pelves undergo growth remodeling
      of the pelvic cavity. Over the same time period, males show significantly greater
      incremental growth in the acetabulum, and females show differentially greater
      growth in the pelvic cavity. At age 18, the pelvis demonstrates a posterior-to
      anterior gradient of increasing dimorphism within the inlet and midplane of the
      pelvic birth canal. As a means of interpreting the effects of natural selection
      on the pelvis, it is argued that appropriate comparisons are within-sample
      comparisons of CVs over time, rather than comparisons between sexes of adult
      coefficients as has been argued by others (Meindl et al. [1985] Am. J. Phys.
      Anthropol. 68:79-85). Analyses of change in coefficients of variation over time
      show evidence of concordantly reduced within-sample variation in 7 pelvic
      dimensions indicating canalization of growth. These results are attributed to the
      effects of stabilizing selection operating on both males and females and include
      transverse diameters of the sacrum, inlet, anterior inferior iliac spines, and
      breadths of the ilium and ischium. Six pelvic dimensions show evidence of
      increased total sample CVs and discordant change in within-sex comparisons of CVs
      as well as differential growth between sexes over time. This pattern is
      indicative of the effects of disruptive selection on the pelvis for
      interacetabular diameter, breadths of the anterior superior and posterior
      inferior iliac spines, public length, and ilium height.

PMID- 8579192
TI  - Euclidean distance matrix analysis: confidence intervals for form and growth
      differences.
AB  - Analysis of biological forms using landmark data has received substantial
      attention recently. Much of the statistical work in this area has concentrated on
      the estimation of average form, average form difference, and average growth
      difference. From the statistical, as well as the scientific point of view, it is
      important that any estimate of a scientifically relevant quantity be accompanied
      by a statement regarding its accuracy. Such a statement is contained in a
      confidence interval. The purpose of this paper is to provide a method to obtain
      confidence intervals for form difference and growth difference estimators. The
      estimators are based on Euclidean distance matrix analysis. The confidence
      intervals are calculated using the model independent bootstrap method. We
      illustrate the method by using three examples: morphological differences between
      samples of craniofacial patients and normal controls using two dimensional data
      from head X-rays, sexual dimorphism of craniofacial morphology in Cebus apella,
      and sexual dimorphism of facial growth in Cebus apella using three-dimensional
      data.

PMID- 8579193
TI  - [Materials on the novel preparation Zoladex. 1 March 1995, Moscow, Russia].

PMID- 8579194
TI  - [The endoscopic treatment of mature teratomas].

PMID- 8579195
TI  - [The surgical treatment of patients with uterine myoma by using endoscopic
      methods and laser technics].
AB  - The advantages and shortcomings of endoscopic and laser myomectomies in
      comparison with conventional myomectomy using laparotomy are discussed. A total
      of 279 patients with uterine myoma were subjected to myomectomy using laparotomy
      with CO2 laser (n = 109), laparotomy without laser (n = 45), laparoscopy (n =
      120), and hysteroscopic removal of submucosal fibroids (n = 5). Comparative
      statistic analysis of the major intraoperative and early postoperative clinical
      parameters indicated that laparoscopic myomectomies are associated with an
      appreciable reduction of blood loss, its duration is the same as that of
      traditional operation, and the postoperative period runs a more benign course
      than after conventional surgery.

PMID- 8579196
TI  - [Antihormones and laparoscopy in the combined treatment of disseminated forms of
      genital endometriosis externa].
AB  - A total of 100 patients with disseminated forms of external genital endometriosis
      were administered multiple-modality treatment including surgery and antihormone
      therapy. Twenty patients with the same diagnosis were controls and subjected to
      surgery alone. The results of treatment assessed on the basis of analysis of the
      clinical course of the disease, status of the menstrual and generative functions,
      drug effects on the central nervous system, hormonal status, and target organs
      (mammary glands and osseous tissue) evidence good potentialities of laparoscopy
      and high efficacy of subsequent therapy with antihormones in the treatment of
      patients with grave forms of endometriosis.

PMID- 8579197
TI  - [An alternative approach to the surgical correction of tubal infertility].
AB  - The authors compare the efficacy of surgical treatment of tubal sterility using
      laparoscopy (133 cases) and microsurgical techniques (120 cases). The results
      were assessed with due consideration for the dissemination of adhesions (first
      second and third-fourth degrees), status of the uterine tubes, and presence or
      absence of chlamydial infection. Surgical correction via an endoscopic access was
      found to be preferable in adhesions of the first-second degree, whereas in
      adhesions of the third-fourth degree surgical interventions are inadvisable.

PMID- 8579198
TI  - [The role of comprehensive examination and laparoscopy in the surgical treatment
      of tubal pregnancy].
AB  - A total of 253 patients were examined and operated on for ectopic pregnancy.
      Eight-six patients were operated on through a laparoscopic access (group 1) and
      167 through a laparotomic access (group 2). The authors assess the diagnostic
      value of echography, measurement of b-subunit of chorionic gonadotrophin,
      puncture of the abdominal cavity through the posterior vaginal vault, and of
      histologic examination of scrapings off the endometrium in a complex of
      examinations of patients with ectopic pregnancy. The results demonstrated the
      advantages of the laparoscopic access over laparotomy as involving lesser
      bleeding to the abdominal cavity and no evident adhesions.

PMID- 8579199
TI  - [Laparoscopy, hysteroresectoscopy and laser surgery in the correction of
      development defects of the genitalia].
AB  - Clinical status, the major parameters characterizing the course of surgery, early
      postoperative period, immediate and late results of treatment are analyzed in 261
      patients. Besides the routine methods, endoscopic methods (laparoscopy and
      hysteroresectoscopy) were used at the principal stages of the operation in 97
      patients, and in 18 more patients CO2 laser was used for metroplasty. Use of
      present-day equipment and methods facilitates surgical repair of developmental
      defects of the genitals, reduces the duration of the operation, decreases blood
      loss, shortens hospital stay, appreciably improves the efficacy of surgical
      treatment, and places the operations for correction of developmental defects
      among those available for surgeons who mastered the endoscopic methods. Hence,
      modern endoscopic methods may be effectively used for both the differential
      diagnosis of developmental defects of the genitals and for surgical repair
      thereof.

PMID- 8579200
TI  - [The determination of CA-125, CA-19-9 and CEA antigens in gynecologic patients
      for differential diagnosis and the assessment of the efficacy of surgical
      treatment and subsequent monitoring].
AB  - Tumor markers CA 125, CA 19-9, and carcinoembryonic antigen (CEA) were measured
      in the blood sera of 396 inpatients of different age. In 139 patients the
      measurements were carried out over time. Hoffman La Roche enzyme immunoassay test
      kits were used. Eight groups of women were tested: controls without gynecological
      diseases, women in need of plastic repair of the genitals, patients with
      inflammatory diseases, with cervical endometriosis, internal endometriosis,
      ovarian endometriosis, uterine myoma, benign ovarian tumors, and malignant tumors
      of the ovaries. The results indicate a relatively high diagnostic value of
      measuring CA 125 in gynecological patients, particularly in those with
      endometriosis. Parallel measurements of three markers in the blood serum (CA 125,
      CA 19-9, and CEA) are more informative for the differential diagnosis of
      endometriosis and malignant tumors. Follow-up of CA 125 concentration may be used
      to assess the efficacy of therapy and help early detect the disease recurrences.

PMID- 8579201
TI  - [Reconstructive plastic operations on the cervix uteri using preserved tissues].
AB  - The authors analyze the results of surgical treatment of 57 patients with third
      degree ruptures of the uterus and high cervicovaginal fistulae operated on with
      the use of preserved lyophilized human dura mater. Control group consisted of 56
      patients with second and third-degree ruptures of the uterus and cervicovaginal
      fistulae operated on by routine methods. Use of dura mater as a biologic
      transplant for plastic repair of the cervix uteri in the above-mentioned patient
      population improved the efficacy of treatment of this condition: good results
      were attained in 52 patients, satisfactory in 4, and were poor in only 1 patient.

PMID- 8579202
TI  - [Surgical laparoscopy in gynecology].

PMID- 8579203
TI  - [Myometrectomy--a method of choice for the therapy of adenomyosis patients in the
      reproductive period].
AB  - Seventy-six patients with adenomyosis were examined using computer-aided
      hysterosalpingography and transvaginal ultrasonic scanning in the "pseudocolor"
      mode. Organ-sparing operation, myometrectomy (removal of the involved myometrium
      with preservation of the uterus) was performed in 8 patients aged 18 to 34. In
      the postoperative period, conservative therapy was administered. Fifty percent of
      patients became pregnant within a year after the operation.

PMID- 8579204
TI  - [The diagnostic importance of the TG test in surgical gynecology].

PMID- 8579205
TI  - [The ribonucleotide reductase content in a uterine myoma].

PMID- 8579206
TI  - [Tumor markers in gynecology].

PMID- 8579207
TI  - [The prevention of adhesion formation in surgical gynecology (the role of suture
      materials and barriers)].

PMID- 8579208
TI  - [Methods of gravitational surgery on the blood in obstetrics and gynecology].

PMID- 8579209
TI  - [The laparoscopic sterilization of women].

PMID- 8579210
TI  - [Early rehabilitative physiotherapy after surgical laparoscopy in gynecology.
      Answers to the questions of practicing physicians].

PMID- 8579211
TI  - [The 14th Congress of the International Association of Gynecologists and
      Obstetricians (Montreal, Canada, 1994)].

PMID- 8579212
TI  - [The surgical treatment of ovarian formations by a laparoscopic approach].
AB  - This study was aimed at assessment of the efficacy of surgical treatment of bulky
      formations in the ovaries. Surgical laparoscopy for benign tumors and tumor-like
      processes in the ovaries was carried out in 548 patients. The operations were
      performed for benign tumors (17%), tumor-like formations (23%), endometrioid
      cysts (16%), polycystic ovaries (14%), gonadal dyskinesia (2%), and stable
      menstrual dysfunction (24%). The size of ovarian formations varied from 2 to 8
      cm. Partial or clinoid resection of the ovaries, adnexectomy, oophorectomy,
      removal of the parovarian cyst, or extended biopsy of the ovaries were carried
      out. The results were good. No relapses were recorded. Blood loss was virtually
      null. The mean duration of an operation was 67.34 +/- 10.5 min. Follow-up of 6
      months to 3 years revealed no adhesions in 34.2% cases and first-degree adhesions
      in 65.8%.

PMID- 8579213
TI  - Neurotransmitters and vulnerability of the developing brain.
AB  - The immature human brain undergoes remarkable organizational changes during
      intrauterine and postnatal life. These changes create potential temporal
      'windows' of selective vulnerability to damage. For example, the temporary
      germinal matrix is vulnerable to hemorrhage in the third trimester fetus and
      premature infant. The immature oligodendroglia present in developing white matter
      of the fetus are also vulnerable to injury producing periventricular
      leukomalacia. Similar changes take place in the synapses that make up the
      infant's neuronal circuitry. In human cerebral cortex, synapses are produced in
      greater than adult numbers by postnatal age 2 years and then reduced over the
      next decade. Over the same period receptors for glutamate, the most important
      excitatory neurotransmitter, change their characteristics to allow them to
      participate in activity dependent synaptic plasticity. For example, the immature
      N-methyl-D-aspartate (NMDA) type glutamate receptor/channel complex, which plays
      important roles in long term potentiation (LTP), neuronal migration and synaptic
      pruning, contains subunits that allow the channel to be opened more easily for a
      longer period than adult channels. These developmental changes make the immature
      brain selectively vulnerable to NMDA receptor overstimulation that can occur
      during hypoxia-ischemia and other insults. Several types of neuropathology in the
      developing brain can be understood on the basis of these organizational
      principles.

PMID- 8579214
TI  - Folate metabolism and neural tube defects.
AB  - Neural tube defects may due to a number of factors acting on a susceptible
      embryo. The most widely accepted is a lack of folic acid at a critical time of
      development. Studies in which folic acid supplements have been given are
      reviewed. The results of these support the policy of giving folic acid, starting
      before conception. The metabolism of folate and vitamin B12 is discussed,
      including specific metabolic disorders; although there is no evidence that these
      play any part in causing neural tube defects. The special problems that occur
      among women taking anti-epileptic drugs are also considered. There are slight
      differences in the recommendations that have been made for supplementation, and
      further studies are needed before there can be complete agreement.

PMID- 8579215
TI  - Cerebral hemodynamics on near-infrared spectroscopy in hypoxia and ischemia in
      young animal studies.
AB  - Using near-infrared spectroscopy the changes of intracranial oxyhemoglobin,
      deoxyhemoglobin, total hemoglobin and cytochrome aa3, which show the progression
      of intracranial oxygenation, hemodynamics and cell metabolism, were recorded
      during prolonged partial hypoxia induced by carbon dioxide (CO2) and nitrogen
      (N2), ischemia induced by hyperventilation, and hypoxia during hypoglycemia in
      neonatal and young rabbits. The reduction of cytochrome aa3 during the terminal
      stage of CO2-induced prolonged hypoxia, hyperventilation and hypoxia in
      hypoglycemia suggests that the redox state of cytochrome aa3 will be changed by
      several combined factors such as oxygen delivery, ATP demand and substrate
      (glucose) delivery.

PMID- 8579216
TI  - Non-radioactive DNA diagnosis for the fragile X syndrome in mentally retarded
      Japanese males.
AB  - A rapid screening test was developed to detect CGG repeat expansion of the FMR-1
      gene causing the fragile X syndrome by a non-radioisotope PCR technique. A biotin
      labeled primer was initially used and the biotin-labeled PCR product was detected
      by means of chemiluminescence. The normal PCR product of around 300 bp was not
      created in the abnormal FMR-1 gene sample with this method. Four positive samples
      were found among those from 226 mentally retarded males, but the CGG repeat
      expansion was shown on Southern blot analysis in only one sample. To eliminate
      false-positive samples, a hybridization method involving a biotin-labeled (CGG)s
      oligonucleotide was developed for the PCR product and the CGG repeat expansion
      could be detected. Finally, 256 mentally retarded males in Japan were examined
      and only 2 abnormal samples were detected. The prevalence of this abnormality was
      less than 1%, which is relatively lower than those reported previously.

PMID- 8579217
TI  - Frequency of the Prader-Willi syndrome in the San-in district, Japan.
AB  - Nineteen cases of the Prader-Willi syndrome were collected in the San-in
      district, in the western part of Japan, and an epidemiological study was carried
      out. The male to female ratio was 1:1.11. Deletion of chromosome 15q11-13 was
      found in seven of 16 patients examined by means of high-resolution chromosome
      banding. The incidence among live-births was estimated to be 6.64 x 10(-5) (1 in
      15,060 live-births) in 1980-1989, and the mutation rate was 3.32 x 10(-5) per
      gene per generation, as determined by a direct method. The prevalence was
      estimated to be 5.72 x 10(-5) (1 in 17,483) in patients under 15 years old, which
      was higher than that in other autosomal dominant diseases (tuberous sclerosis and
      congenital myotonic dystrophy) also studied in the San-in district. A birth-order
      effect was revealed and a slightly significant difference was found as to the
      fathers' age between the patients and their normal siblings. The results of these
      two tests are in accord with the recent discovery that this syndrome is caused by
      paternal chromosomal aberrations.

PMID- 8579218
TI  - Studies on cerebrospinal fluid kynurenic acid concentrations in epileptic
      children.
AB  - Kynurenic acid (KYA), the only known endogenous antagonist of the excitatory
      amino acids, is a metabolite of kynurenine. In the present study the levels of
      KYA were measured in the cerebrospinal fluid (CSF) of epileptic children and age
      matched controls to investigate the relationship between various forms of
      epilepsy and KYA levels. CSF samples from four patients with West syndrome (WS),
      four patients with epilepsy with grand mal seizures on awakening (EGSA), and four
      patients with childhood epilepsy with occipital paroxysms (CEOP) were collected
      by lumbar puncture before treatment. The concentration of CSF KYA was analyzed by
      HPLC with electrochemical detection and compared with those of age-matched
      controls. The levels of CSF KYA were significantly lower (P < 0.05) in patients
      with WS compared with controls. The levels of CSF KYA in patients with EGSA and
      with CEOP did not differ significantly from control levels. These results suggest
      that the presence of seizures in WS is associated with altered kynurenine
      metabolism. The possibility that seizures in WS may be related to decreased
      production of KYA is discussed.

PMID- 8579219
TI  - Treatment of electrical status epilepticus by short diazepam (DZP) cycles after
      DZP rectal bolus test.
AB  - The effects of rapid rectal diazepam introduction (DZP test) were investigated in
      43 patients (age range 5 months-14 years) with electrical status epilepticus
      (ESE) undergoing EEG monitoring. A remission of the paroxysmal activity was
      obtained in 58% of cases, a negative response in 42%, particularly in
      hypsarrhythmic patterns. DZP test responders were aged over 12 months with
      organized paroxysmal EEG patterns, in particular with ESE during sleep (ESES).
      The patients who responded to the DZP test underwent short cycles (3-4 weeks) of
      relatively high dosage DZP (0.5-0.75 mg/kg). The response to treatment was
      positive in 64%, particularly in ESES conditions. 56% of responders to the DZP
      test but not to DZP therapy (five out of nine patients) presented a significant
      mental retardation; maturational factors were also likely to be present.

PMID- 8579220
TI  - Benign convulsions with mild gastroenteritis: a report of 10 recent cases
      detailing clinical varieties.
AB  - To better define the characteristic clinical features of benign convulsions with
      mild gastroenteritis, recently recognized as a new entity in Japan, we reviewed
      all the 10 patients we have seen from 1992 to 1994. The clinical features have
      been previously reported in the literature to be afebrile generalized tonic
      clonic seizures occurring between the first and the fifth sick day of mild
      gastroenteritis. In our series, four of 10 patients had convulsions before the
      onset of gastroenteritis. Overall, seizures were mostly brief and often
      repetitive occurring in cluster (19 seizures/10 episodes). Among these, a
      prolonged or partial seizure was frequently observed. In six of the 10 patients,
      the seizure type changed during an episode: from generalized to partial seizures
      (n = 2), from partial to generalized seizures (n = 2), or from partial to another
      type of partial seizures (n = 2). None in our series experienced a recurrence
      episode of afebrile convulsion during follow-up. These findings suggest that
      benign convulsions with mild gastroenteritis exhibit some variations in their
      clinical manifestation.

PMID- 8579221
TI  - Classification of hydrocephalus and outcome of treatment.
AB  - PURPOSE: Retrospective analysis in cooperative study of hydrocephalus at
      institutions of members of the Research Committee on Intractable Hydrocephalus
      sponsored by the Ministry of Health and Welfare of Japan was performed to
      determine the functional prognosis for all types of hydrocephalus and thus to
      clarify the outcome. METHODS: In preparation of this study, we have proposed the
      definition, clinical classification and diagnostic criteria of hydrocephalus. We
      have classified non-tumoral hydrocephalus into eight types based on its etiology
      and the time of onset. To establish the diagnosis in each type of hydrocephalus,
      we have set up inclusion and exclusion criteria, as well as supplementary
      criteria which are useful for its diagnosis. RESULTS: Analysis of the 1450 cases
      of hydrocephalus of various etiologies stored in the data base obtained from the
      study for each type of hydrocephalus revealed that following types and conditions
      were associated with a neurologic deficit: (1) early fetal hydrocephalus, (2)
      overt neonatal hydrocephalus, (3) hydrocephalus associated with such severe brain
      malformations as hydranencephaly, holoprosencephaly and lissencephaly, (4)
      hydrocephalus associated with severe brain damage, (5) hydrocephalus associated
      with epilepsy, (6) hydrocephalus shunted late after detection, and (7)
      hydrocephalus complicated by a shunting operation. CONCLUSION: The postnatal
      functional outcome was significantly poor in fetal hydrocephalus diagnosed in the
      early gestation. Childhood onset hydrocephalus showed a poorer outcome than adult
      hydrocephalus.

PMID- 8579222
TI  - Intradural spinal meningioma in a 5-year-old female.
AB  - The case of a 5-year-old female with an intradural spinal meningioma is
      presented. She showed slowly progressive muscle weakness of the lower extremities
      commencing at 3 years. Spinal magnetic resonance imaging (MRI) demonstrated an
      intradural mass extending from the eleventh thoracic vertebra to the fifth lumbar
      vertebra, which was excised totally by means of laminoplasty. The surgical
      procedure brought a gradual improvement in her gait. This case is unusual because
      of the tumor's location (lumbar) and origin (cauda equina), and because of the
      onset at a relatively young age.

PMID- 8579223
TI  - Perinatal intracranial hemorrhage due to severe neonatal alloimmune
      thrombocytopenic purpura (NAITP) associated with anti-Yukb (HPA-4a) antibodies.
AB  - Neonatal alloimmune thrombocytopenic purpura (NAITP) is one of the causes of
      thrombocytopenia in the newborn period. The thrombocytopenia is caused by
      maternal transplacental antiplatelet alloantibodies. We report a case of NAITP in
      a newborn infant having subarachnoid hemorrhage. Examination of platelet
      antibodies revealed anti-Yukb, that is, human platelet antigen (HPA)-4a
      incompatibility. Cranial ultrasound and brain magnetic resonance imaging revealed
      subarachnoid hemorrhage in the temporal region inferior to the cephalohematoma.
      The lesion seemed to have been sustained during delivery. The patient was treated
      with high-dose gamma-globulin and several transfusions of random donor platelets
      and showed a good clinical course. This is the second reported case of NAITP
      associated with the Yuk antigen system having intracranial hemorrhage.

PMID- 8579224
TI  - Serial neuroimages of acute necrotizing encephalopathy associated with human
      herpesvirus 6 infection.
AB  - A previously healthy 8-month-old girl developed exanthem subitum and acute
      encephalopathy with status epilepticus, quadriplegia and bilateral abducens nerve
      palsies. Human herpesvirus-6 DNA was found in the cerebrospinal fluid by the
      polymerase chain reaction at the acute stage. Cranial computed tomography showed
      low density areas in the thalami and in the cerebellar and abducens nuclei. The
      distribution of the lesions was consistent with acute necrotizing encephalopathy.
      As for the thalamic lesions, a T2 weighted magnetic resonance image on the 24th
      day of the illness demonstrated low signal intensity surrounded by high
      intensity; 99mTc-ECD SPECT showed hypoperfusion, which suggested irreversible
      tissue damage. The patient is now 1 year 6 months old and has spastic
      quadriparesis with mental retardation and abducens nerve palsies.

PMID- 8579225
TI  - Mild form of acute herpes simplex encephalitis in childhood.
AB  - We describe two patients, aged 3.5 years and 15 years, with a mild form of herpes
      simplex encephalitis (HSE). The disease was characterized by convulsions and
      lymphocytic pleocytosis in the cerebrospinal fluid (CSF). Involvement of herpes
      simplex virus (HSV) was established by antibody measurements in serum and CSF.
      Recovery was complete with no antiviral drug administration. It appears that
      scrutinized serological work-up would widen our concept of mild forms of HSE,
      with a better prognosis and complete recovery.

PMID- 8579226
TI  - Autism, macrocrania and epilepsy: a syndrome?

PMID- 8579227
TI  - [Kikuchi's necrotizing lymphadenitis. Clinical and pathological study of a new
      case].
AB  - Contribution to the topic with the case of a woman, 24, admitted in our ENT
      Department for exam and treatment of multiple right sided adenopathies of the
      neck. The histopathological study was consistent with diagnosis of Kikuchi's
      necrotizing lymphadenitis. This is a new clinicopathologic entity first
      described, 1972, by Kikuchi, of unknown etiology, an a picture characterized for
      painful cervical lymphadenitis presented in young women and healing spontaneously
      after 2-3 months course. We want to emphasize in this paper the scarcity of cases
      published and the difficulties arising when dealing with the differential
      diagnosis with lympho-proliferative malignancies as well.

PMID- 8579229
TI  - [Mediastinitis secondary to Ludwig's angina. One case report].
AB  - Ludwig's angina is a cellulitis, usually of odontogenic origin, involving the
      submandibular space. The number of cases has been heavily lowered since the
      introduction of antibiotherapy. The treatment consists in an aggressive
      antibiotherapy and, sometimes, surgical drainage. Complications are: acute
      respiratory obstruction and spreading of the infection through the neck spaces
      till the mediastinum. We report one cas complicated with mediastinitis which
      diagnosis was based in radiological data, basically provided for TAC, The
      treatment required surgical drainage and antibiotherapy.

PMID- 8579228
TI  - [Cystic adenoid carcinoma. Review of last five years in our ENT department (1987
      1991)].
AB  - We present 4 cases of adenoid cystic carcinoma from different locations (parotid,
      submaxillary, larynx and auditory duct) and we underline the supraglottic origin
      of one of them. We point out the good clinical behaviour of this carcinoma, with
      a long tested survival, more than 5 years, in 2 of our cases. All of them showed
      morphological features independently of the sitting.

PMID- 8579230
TI  - [Bilateral facial palsy, Bell's type].
AB  - Report of one case of Bell's peripheral bilateral facial paralyse in a woman, 62
      year-old. This bening acute cranial polyneuritis is a frequent complaint, but its
      bilaterally makes the interest of the case. The clinical course of the illness
      parallels that of the unilateral cases, both having a good pronostic.

PMID- 8579231
TI  - [Cystic formations of the maxilla. Case report].
AB  - The case of a man, 28, addressed to our ENT-Department complaining of pain and
      swelling of the left half of the face is presented. After X-Ray and tomographic
      study the diagnosis of an included tooth inside the maxillary sinus, accompanied
      by one cyst, is evidenced. In addition a canine tooth as well included on the
      floor of the nose and under the lower homonyme turbinate, is disclosed. Through
      sinusal approach, via Caldwell-Luc, are removed the lesions encountered. Then,
      the AA., attempt to classify the group of several cystic structures of maxillary
      sitting, aiming at unify the nomenclature of this pathology, and made a brief
      description of each type.

PMID- 8579232
TI  - [Intranasal encephalocele].
AB  - We present a case of an intranasal encephalocele in a 6-year old girl, that
      appears as an intranasal mass with CSF rhinorrhea. The surgical treatment is
      described, specially the extracranial step through a paralateronasal via. The
      embryogenesis, classification, diagnosis and management of these rare congenital
      lesions are discussed.

PMID- 8579233
TI  - [Giant dermoid cyst of the floor of the mouth].
AB  - Report the case of a young feminine patient, 17, presenting since the first year
      of her life, a swelling of few milimeters diameter, close to the frenulum of the
      tongue, with progressive enlargement. At examination is verified a swelling about
      10 cms. diameter filling the whole ground of the mouth and pulling backwards the
      tongue and producing a clear protrusion in the suprahyoid region. After lateral X
      ray of the neck, echography and cervical TAC, surgery is advised with the
      suspicion of ranula sublingualis. Removal of the tumor through medial cervictomy,
      finding, besides the main mass, a second one about 3 cms. diameter. The
      histopathological diagnosis of a cyst of the thyroglossal duct, its sitting place
      and the clinical course, compelled the AA. to review the slides and being obvious
      the presence of sebaceus glands, they change the prior diagnosis for that of
      dermoid cyst.

PMID- 8579234
TI  - [Solitary plasmocytoma of the mandible. Report of one case and review of the
      literature].
AB  - Between the plasma-cell neoplasms the solitary osseous plasmocitoma represents a
      low percentage of the whole totality. Unlike the multiple myeloma the
      plasmocytoma is a lesion potencially curable. The diagnose criteria that must
      fulfil these lesions are detailed. The AA. report a case sitting in the lower
      jaw. Review of the previous 28 cases communicated in the anglo-saxon literature.
      Special attention is paid to the radiotherapy on this sickness.

PMID- 8579235
TI  - [The effect of gingko biloba on cochleovestibulary pathology of vascular origin].
AB  - The AA. of the present paper recall the clinical and functional results of this
      therapy in a group of 70 patients complaining of vertigo. The Gingko biloba
      extract (4 ml/12 h per mouth) has been continued during 6 months. Neck and
      vertebrobasilar insufficiency were predominant causes. Six months later
      statistically significant changes regarding the decrease of intensity of tinnitus
      and vertigo crises were confirmed. Besides favorable alterations in the
      peripherical symptomatology as a relative hearing improvement turned up.

PMID- 8579236
TI  - [Significant differences in brainstem auditive potentials, in a juvenile normal
      hearing population].
AB  - The aim of this paper is an attempt to show up the possible variations of
      latencies of the waves of brainstem auditory evoked potentials (SP), in daily
      practice, without actual otoneurological pathology. The AA. made this study in 62
      normal hearing ears from healthy young people with the BSP derived tracings at
      several intensities of stimulation (60, 75 and 90 db) with the help of two
      different equipments. They considered the mean and standard latency deviations of
      I, III and V waves and their intervals and found out that the maximum and minima
      values were compatible with any otoneurological pathology, that they could't
      prove afterwards.

PMID- 8579238
TI  - [Paleopathology].

PMID- 8579237
TI  - [In vitro studies of the human endometrium. Mechanisms of decidualization of the
      endometrial stroma].

PMID- 8579239
TI  - [Quality of life in oncologic gynecology. The dilemma: the obligation and the
      choice].

PMID- 8579240
TI  - [Genetic polymorphism and immune diseases].

PMID- 8579241
TI  - [Specification of heart forming elements].

PMID- 8579242
TI  - [Discomalleolar ligament: anatomical reality or fiction].

PMID- 8579243
TI  - [The parotid gland is capable of assuming hypophyseal functions: 2].

PMID- 8579244
TI  - [Gene therapy of malignant brain tumors].

PMID- 8579245
TI  - [Molecular biology of infections caused by HIV and other hepatotropic viruses].

PMID- 8579246
TI  - [Hazards of insect vectors of parasites: from theory to practice].

PMID- 8579247
TI  - Three-dimensional structure of tubular networks, presumably Golgi in nature, in
      various yeast strains: a comparative study.
AB  - BACKGROUND: In the yeast Saccharomyces cerevisiae, the Golgi apparatus consists
      of discrete units distributed throughout the cytoplasm. When such units are
      examined in three dimensions, in relatively thick sections prepared for the
      electron microscope, they usually appear as small tubular networks with a stained
      material accumulating in dilations located at the junctions of membranous
      tubules. To see whether such tubular networks are observed in other yeast
      species, the three-dimensional structure of organelles in eight additional yeast
      strains, endowed with diverse biological properties, are examined. METHODS: Yeast
      strains were grown at 24 degrees C in YPD medium (2% Bactopeptone, 1% Bactoyeast
      extract, and 2% glucose). Cells that were examined by electron microscopy came
      from exponentially growing cultures grown in a shaking water bath and maintained
      at a OD 600 (optical density at 600 nm) of 0.5. Cells were fixed in a fixative
      containing 2% glutaraldehyde in 0.1 M cacodylate buffer pH 7.4 and 0.8 M
      sorbitol. They were then treated for 15 min in 1% sodium metaperiodate and
      postfixed for 1 hr in potassium ferrocyanide-osmic acid. They were preembedded in
      agarose prior to dehydration and finally embedded in Epon. In these conditions,
      the preservation of cell organelles was improved and the cytoplasmic retraction
      from the cell wall was minimized. Photographs of sections tilted at +/- 15
      degrees from the 0 degrees position of the goniometric stage were used to prepare
      stereopairs from which the three-dimensional configuration of the organelles was
      visualized. RESULTS: In all yeast strains, tubular networks appeared as separate
      elements or units disperse throughout the cytoplasm. Each unit consisted of
      anastomosed membranous tubules. In some strains such as Saccharomyces cerevisiae,
      Zygosaccharomyces rouxii, or Saccharomyces pombe, such units appeared mainly as
      polygonal networks of intensely stained membranous tubules. Along these networks,
      distensions filled with stained material were similar in size to nearby secretory
      granules, suggesting that the latter formed by fragmentation of the tubular
      networks. In Hansenula polymorpha, Pichia pastoris, and Debaryomyces hansenii,
      networks of anastomosed tubules were closely superposed to each other and formed
      parallel arrays reminiscent of the stacks of Golgi saccules seen in mammalian
      cells. However, in contrast to what is usually found in the latter, the layers
      making up the parallel arrays in yeasts, were clearly continuous to each other.
      In other strains, i.e., Kluyveromyces lactis, Candida albicans, and Candida
      parapsilosis, the situation was intermediate and their cytoplasm contained only
      arrays of small size with two or at most three superposed layers of membranous
      tubules. Small vesicles in the 30-50 nm range were rarely encountered in most
      yeast strains. CONCLUSIONS: It is therefore concluded that tubular networks,
      presumably Golgi in nature, are present in all yeasts examined so far. Yet, in
      some strains, these tubular networks may be arranged in parallel arrays or
      stacks.

PMID- 8579248
TI  - Type VI collagen in mouse masseter tendon, from osseous attachment to
      myotendinous junction.
AB  - BACKGROUND AND METHODS: The association of masseter tendon type VI collagen with
      other extracellular matrix (ECM) components was examined from osseous attachment
      to myotendinous junction by immunohistochemistry and transmission electron
      microscopy with ATP treatment and enzyme digestion. RESULTS: In the tendon
      proper, fibrocytes extended their processes among bundles of striated collagen
      fibrils and associated with adjacent cells through amorphous materials, thus
      forming a three-dimensional network. The amorphous or filamentous material was
      observed around the fibrocyte cell body and along the cell processes, where the
      localization of type VI collagen was confirmed by immunohistochemistry using anti
      type VI collagen antibody. After treatment with 20 mM adenosine 5'-triphosphate
      (ATP), 100 nm periodic fibrils, an aggregated form of type VI collagen, were
      formed in the place where amorphous or filamentous material was present before
      the treatment. In myotendinous junction, the ATP-aggregated periodic fibrils were
      observed to associate with the external lamina of the muscle cells as well as
      among junctional tendon collagen fibrils. In the tendon-bone boundary, ATP
      aggregated periodic fibrils were observed around fibrocartilage-like cells in the
      uncalcifying area but not in the calcification front. Prolonged ATP treatment or
      hyaluronidase predigestion caused the formation of type VI collagen periodic
      fibrils in the area near the calcified matrix. CONCLUSIONS: The distribution of
      type VI collagen in mouse masseter tendon is different in different anatomical
      position. This may reflect the different functional demand for this collagen.

PMID- 8579249
TI  - Ultrastructural changes of secretory cells of salamander lingual salivary glands
      under varying conditions.
AB  - BACKGROUND: In general the ultrastructure of secretory cells can be modified
      under secretory stimulated and non-stimulated conditions. The ultrastructure of
      the lingual salivary glands of hibernating salamanders in the natural environment
      was examined and compared to those of fasted and fed animals kept in the
      laboratory. METHODS: Hibernating salamanders of the species Hynobius tokyoensis
      were collected from the natural environment during the winter breeding season and
      sacrificed for this study. One group was sacrificed immediately, another group
      was kept under fasted condition, and another group was regularly fed; both of the
      latter groups were kept at room temperature for 1 month and then sacrificed. The
      tongue was fixed for electron microscopy and processed by conventional method,
      and semithin sections were histochemically examined for glycoconjugates. RESULTS:
      The lingual salivary glands of this salamander species were composed of simple or
      often branched tubular glands opening onto the dorsal surface of the tongue. The
      secretory cells which composed their terminal portions were all columnar in
      morphology and histochemically mucous in nature. Under hibernation or prolonged
      fasting at room temperature, the mucous granules of these columnar secretory
      cells were decreased in number and the Golgi apparatus appeared inactive. A
      conspicuous structural peculiarity was multiple fingerprint-like structures of
      the rough-surfaced endoplasmic reticulum (RER). Most of these membranes were
      composed of stacks of tightly packed cisternae. Under regular feeding, the mucous
      granules were closely packed in the cytoplasm of the secretory cells and the
      basal nucleus was slightly enlarged. The Golgi apparatus showed progressive
      activation with distended saccules. The unique membranous arrangement of the RER
      which was observed in the fasting animals was completely absent, and the
      cisternae were irregular in width with considerable variation of the
      intercisternal spaces. CONCLUSIONS: The tongue of the salamander H. tokyoensis
      has numerous tubular salivary glands which are mucous in nature. The architecture
      of the organelles in the secretory cells is subject to modification in response
      to the cellular metabolism.

PMID- 8579250
TI  - Special relationship between mitochondria and hypolemmal nerve terminals in
      salivary glands of some bats.
AB  - BACKGROUND: Hypolemmal nerve terminals, which are abundant in many types of
      salivary glands, are naked axons that have penetrated the basement membrane to
      take up a position between adjacent parenchymal cells. Although they may form
      vesicle-filled varicosities, there usually are no obvious morphological
      indications as to which cell actually is being innervated. METHODS: Specimens of
      over 200 species of bats were live-trapped and their major salivary glands
      extirpated and prepared for electron microscopic examination. RESULTS: In 13
      species of bats out of the more than 200, mitochondria-hypolemmal nerve terminal
      complexes were observed in different sites in different salivary glands. In these
      13 species, mitochondria in epithelial cells that abut nerve varicosities are
      closely applied to the plasma membranes of their cells to follow the contours of
      these nerve elements. The complexes so formed often consist of a varicosity
      flanked by two mitochondria in separate cells. In intensely innervated glandular
      segments, mitochondria may be opposed not only to varicosities, but to the axonal
      portions of these nervous elements as well. CONCLUSIONS: The physiological
      significance of such complexes is unknown; it is conceivable that the
      mitochondria facilitate signal transmission or play a role in local calcium
      homeostasis related to nerve function.

PMID- 8579251
TI  - Morphomechanics of the humero-ulnar joint: I. Joint space width and contact areas
      as a function of load and flexion angle.
AB  - BACKGROUND: Previous studies have shown that the trochlear notch is deeper than
      necessary for an exact fit with the humerus. However, humero-ulnar joint space
      width and contact areas have so far not been quantified for variations in the
      load and angle of flexion. METHODS: Six fresh cadaveric specimens were
      investigated at 30 degrees, 60 degrees, 90 degrees, and 120 degrees of flexion
      and at loads of 25 and 500 N, simulating resisted elbow extension. The joint
      space width and contact were determined, using polyether casting material.
      RESULTS: At 25 N all joints made contact in the ventral and dorsal aspects of the
      articular surfaces, whereas in the depth of the trochlear notch the joint space
      was on average between 0.3 and 2.8 mm wide, with some variation between
      individuals. At 500 N the joint space width was considerably reduced and the
      contract areas expanded towards the depth of the notch. The size of the dorsal
      contact areas was significantly smaller at 30 degrees and that of the ventral
      ones at 120 degrees, their ventro-dorsal ratio decreasing considerably from 30
      degrees to 120 degrees (p < 0.01). CONCLUSION: These results indicate that the
      size of the contact areas depends to a slight extent on the joint position, but
      that at all loads and flexion angles a bicentric contact and an important central
      joint space width emerge because of the concave incongruity of the joint. These
      data may be used for numerical calculations, analysing the effects of incongruity
      on the joint stress and on the functional adaptation of the subarticular tissues.

PMID- 8579252
TI  - Morphomechanics of the humero-ulnar joint: II. Concave incongruity determines the
      distribution of load and subchondral mineralization.
AB  - BACKGROUND: A deeper joint socket (concave incongruity) is found at most angles
      of flexion of the humero-ulnar joint and maintained over a wide range of
      physiological loading. It is, however, unclear how far this incongruity affects
      the distribution of load and subchondral mineralization of this joint as compared
      with a congruous configuration. METHODS: Two nonlinear, axisymmetrical finite
      element models with two cartilage layers were constructed, one congruous and one
      incongruous, with a joint space of realistic magnitude. The distribution of
      subchondral mineralization was determined by computed tomography
      osteoabsorptiometry in the same six specimens that were investigated in the first
      part of the study, and compared with the biomechanical data obtained there and
      the predictions of the models. RESULTS: In the congruous case, the center of the
      socket is highly loaded, whereas the periphery does not experience mechanical
      stimulation. A central bone density maximum is predicted. With concave
      incongruity the position of the contact areas shifts from the joint margin
      towards the center as the load increases, and the peak stresses are considerably
      lower. A bicentric ventro-dorsal distribution pattern of subchondral
      mineralization is predicted, and this is actually found in the six specimens.
      CONCLUSIONS: Concave incongruity is shown to determine load transmission and
      subchondral mineralization of the humero-ulnar joint. It is suggested that this
      shape leads to a more even distribution of stress, provides intermittent
      stimulation of the cartilaginous tissue, and has beneficial effects on the
      metabolism, nutrition, and lubrication of the articular cartilage during cyclic
      loading.

PMID- 8579253
TI  - Exocytosis of secretory granules in the juxtaglomerular granular cells of
      kidneys.
AB  - BACKGROUND: There is little agreement as to the secretory process of renin
      granules in juxtaglomerular granular cells (JG cells) of kidneys, although a
      large number of studies of the regulation of renin secretion have been reported.
      METHODS: The structural correlation between the stimuli and the secretory process
      was examined in mouse JG cells on renal cortical slices incubated with the beta
      adrenergic agonist, isoproterenol; the loop diuretic, furocemide; the Ca2+
      chelator, EGTA; and the actin filament-disrupting agent, cytochalasin B. RESULTS
      AND CONCLUSIONS: Treatment with isoproterenol (10(-5)-10(-3) M) or furocemide
      (10(-3) M) in Ca(2+)-containing medium did not significantly affect the
      ultrastructure of JG cells. In slices incubated with isoproterenol or furocemide
      in the Ca(2+)-free medium, JG cells occasionally contained a few electron-lucent
      granules at the cell periphery in addition to the electron-dense mature granules
      observed in the control slices. On rare occasions, the JG cells displayed omega
      shaped cavities with electron-lucent matrices, a feature similar to the contents
      of electron-lucent granules. Cytochalasin B markedly promoted the effects of
      these stimulants in Ca(2+)-free medium. These findings suggest that participation
      of actin filament disassembly in the exocytotic process of the mature granules in
      JG cells.

PMID- 8579254
TI  - Culture of bovine oviduct epithelial cells (BOEC).
AB  - BACKGROUND: Bovine oviduct epithelial cells are widely used in co-culture
      experiments to improve early embryonic development and in vitro fertilization in
      embryo transfer programmes for domestic animals. METHODS: The present study
      compares different methods for harvesting and culture of bovine oviduct
      epithelial cells in order to optimize handling. Bovine oviduct epithelial cells
      were mechanically or enzymatically isolated and cultured on glass, on permeable
      membranes, or in suspension. Growth of the cells and their state of
      differentiation was examined by means of classical staining methods,
      immunohistochemistry and electron microscopy. RESULTS: Initial cell suspensions
      contained sheets of ciliated and nonciliated (secretory) cells; 24 h after
      seeding, free floating epithelial cells formed vesicles with cilia on their
      external surface. First adhesion of cells was seen 72 h after seeding. Later on,
      cells grew continuously and confluent monolayers were formed after 7 days.
      Results were identical after mechanical or enzymatical cell harvesting and were
      identical on both substrata tested, i.e., on glass and on permeable membranes.
      Light and electron microscopy proved the monolayers to resemble a polarized,
      simple, cuboidal to columnar epithelial membrane with intact junctional complexes
      and numerous apical microvilli. Their epithelial nature was established by
      immunostaining for cytokeratins. Cilia were missing and secretory granules were
      scarce. A layer of acidic glycoprotein material was demonstrated on the apical
      surface. Monolayers of bovine oviduct epithelial cells stored lipid droplets and
      large quantities of glycogen. About 50% of the seeded cells did not adhere but
      survived in the culture medium as free floating cells. These suspended cells
      maintained morphological criteria of differentiation (cilia and secretory
      granules) until day 12 of culture. Proliferation rates of cultivated cells were
      determined by counting mitoses and by immunostaining with MIB1 antibody. Results
      showed coincidence of rapid proliferation and morphological dedifferentiation of
      monolayers. Suspended cells, by contrast, did not proliferate but retained
      cellular differentiation under identical culture conditions. CONCLUSIONS: The
      results strongly suggest that monolayers of bovine oviduct epithelial cells will
      not fully substitute for original oviduct epithelium when used in co-culture
      experiments after in vitro fertilization.

PMID- 8579255
TI  - Three-dimensional structure of the bronchial microcirculation in sheep.
AB  - BACKGROUND: The bronchial circulation affects both pulmonary vascular and airway
      activity. Fundamental to understanding the role of the bronchial microcirculation
      in health and disease is understanding its anatomy. This study sought to identify
      specific structural elements that might contribute to the drop that occurs
      between the systemic blood pressure of the bronchial artery and the low pressure
      of the pulmonary bed into which the bronchial circulation flows and to better
      describe the connections of the bronchial and pulmonary circulations. METHODS: To
      do this, the lungs of five sheep were cast by injecting a resin through bronchial
      and pulmonary arteries. After taking samples for light microscopy, the tissue was
      digested and the casts were viewed with a scanning electron microscope. RESULTS:
      Casts of extrapulmonary bronchial arteries were structurally similar to other
      systemic arteries. Tortuous ones spiraled around bronchi and large blood vessels.
      Intrapulmonary bronchial arteries, about 100-300 microns in diameter, had sharp
      branching and deep focal constrictions with great rugosity that completely shut
      off the flow of the resin. These vessels correspond to the Sperrarterien
      described by von Hayek (and could cause the resistance associated with the
      pressure drop). Vasa vasorum ran in the walls of intrapulmonary pulmonary
      arteries for a variable distance before they entered the lumens of the pulmonary
      arteries. The smallest blood vessel found that was supplied with vasa vasorum was
      a bronchial artery 42 microns in diameter. Capillary-like networks with large
      luminal diameters were found on the pleural surface. CONCLUSIONS: Scanning
      electron microscopy of microvascular casts provides a fresh description of the
      bronchial circulation, further delineates the communications of these two
      circulations, and may structurally account for some pressure drop between the
      bronchial and pulmonary circulations.

PMID- 8579256
TI  - Atrioventricular valves of the mouse: III. Collagenous skeleton and myotendinous
      junction.
AB  - BACKGROUND: The leaflet tissue of the mouse atrioventricular (AV) valves contains
      a system of wavy collagen bundles that organize like tendons, orientate along
      lines of tension, and constitute an essential component of the valve tissue. The
      organization of these bundles is different in the two AV valves, reflecting
      differences in the anatomy of the entire valvular complex. Further insights into
      this kind of organization are needed to gain a complete understanding of the
      functional anatomy of the mouse AV valves. METHODS: The endocardial covering of
      the mouse AV valves (from 21 days to 1 year of age) was eliminated by the
      sonication or the maceration method. This allowed us to study in situ the
      organization of the collagenous valve skeleton, as well as the structure of the
      myotendinous junction. RESULTS: The leaflets of the two AV valves are formed by a
      fibrous layer (on the ventricular side) and a spongy layer (on the atrial side).
      The fibrosa is formed by undulating collagen bundles that organize and orientate
      differently on the right and left sides. The spongiosa is formed, on both sides,
      by a loose network of thin collagen fibers with no apparent orientation.
      Myocardial cells in the papillary muscles of the tricuspid valve are elongated
      and show cone-shaped tips. Collagen fibers attach to the myocyte surface.
      Collagen struts and thin septa can also be recognized. On the other hand, the
      collagenous components of the mitral leaflets attach tangentially to the mitral
      papillary muscles. On the two sides, the myocytes appear to be ensheathed in a
      layer of collagenous tissue. The sheaths are formed by circularly arranged fibers
      and appear to be tightly interconnected. CONCLUSIONS: The differences in the
      collagenous organization between the two AV valves reflect differences in the
      gross anatomy of the valves. The attachment of collagen to the papillary myocytes
      in the tricuspid valve resembles that of a typical myotendinous junction.
      However, the collagen-muscle junction in the mitral valve is more similar to the
      structure of a pennate muscle. The collagen matrix of the heart has been divided
      into endomysial, perimysial, and epimysial components. The presence of sheaths
      housing individual myocytes and capillaries, struts, and thin septa, corresponds
      to the endomysium. The absence of perimysial septa, which aggregate myocytes into
      groups, is striking, but this may just be a species difference. The
      appropriateness of the term epimysium, as applied to the heart, is discussed.

PMID- 8579257
TI  - Complex structure of the common carotid artery of sheep.
AB  - BACKGROUND: Mechanical properties of blood vessels are dictated by the vessel
      wall structure. In many large conduit vessels the tunica media is a sheath of
      circular musculature and the tunica adventitia a layer of fibrous connective
      tissue with limited longitudinal extensibility. In contrast, the carotid artery
      of the sheep displays in each tunica a more complex architecture of muscle and
      connective tissue. METHODS: Vessels collected from ewes were measured and
      processed for light microscopy and for transmission electron microscopy. RESULTS:
      Layers of histologically different materials are found within the tunica intima,
      media and adventitia. (1) The tunica media is made of circumferentially arranged
      muscle cells markedly different at different depths. In the innermost third of
      the media, muscle cells are small and with irregular profiles, the cells are
      widely separated, and the extracellular material is abundant and composed mainly
      of elastic fibres. In the outermost third, muscle cells are larger and with more
      regular profiles, the cells are relatively close to each other and the
      extracellular material is sparse and consists mainly of collagen fibrils. (2) A
      small number of fibroblasts is found in all parts of the media amongst the
      preponderant muscle cells. (3) The intima contains fibroblast-like cells and
      longitudinally arranged muscle cells. (4) The adventitia contains a thick layer
      of collagen and elastic fibres; external to this, it displays a conspicuous
      musculature, made of large bundles of longitudinal muscle. CONCLUSIONS: The
      carotid artery of the sheep presents in all three coats of its wall features
      which are at variance from those in the better known vessels of small laboratory
      animals. The presence of many layers of material within the wall, the
      heterogeneity of the tissues found, and the occurrence of an extensive
      longitudinal musculature, have important effects on the mechanical properties of
      the vessel.

PMID- 8579258
TI  - Dendritic cells in the bursal follicles and germinal centers of the chicken's
      caecal tonsil express vimentin but not desmin.
AB  - BACKGROUND: Immunohistochemical studies with anti-vimentin and anti-desmin
      monoclonal antibodies were designed to determine the origin of bursal secretory
      dendritic cells (SDC) and follicular dendritic cells. METHODS: The binding sites
      of anti-vimentin, anti-desmin, and anti-chicken-IgG specific monoclonal
      antibodies were visualized with a biotinylated anti-mouse-IgG, ABC Elite kit, and
      4-chloronaphthol. Cells were double stained (anti-vimentin and rabbit anti
      chicken-IgG Fc) to determine if the vimentin positive cells possessed surface
      IgG. RESULTS: Vimentin positive cells were observed in the cortex and medulla of
      the bursa and germinal center and lymphoepithelial compartment of the caecal
      tonsil. The mesenchymal reticular cell, the basic supporting cell of the germinal
      center, was stained prominently by anti-vimentin and anti-desmin. Both antibodies
      stained the bursal cortex but only anti-vimentin bound the bursal secretory
      dendritic cell of the medulla. In addition to being vimentin positive and desmin
      negative, the bursal secretory dendritic cell possessed and the follicular
      dendritic cell appeared to possess IgG on their surfaces. In all the
      observations, B-cells were vimentin negative. CONCLUSION: These studies suggest
      that follicular dendritic cells and mesenchymal reticular cells in the caecal
      tonsil's germinal centers may be functionally different cell populations while
      the bursal secretory dendritic cell and follicular dendritic cell of the caecal
      tonsil may have a common origin.

PMID- 8579260
TI  - Comparison of skin-tissue tensions using the composite and the subcutaneous
      rhytidectomy techniques.
AB  - Controversy as to benefits, risks, and long-term durability of the subcutaneous
      rhytidectomy as compared with the composite and the subcutaneous
      musculoaponeurotic system (SMAS) rhytidectomy procedures has persisted over the
      last several years. Conventional surgical wisdom holds that deep-tissue support
      would provide both immediate and long-term benefits in rhytidectomy patients.
      Recent investigations have shown that deep-tissue support using the SMAS
      technique decreases epidermis closure tension. This effect has potential
      implications on vascularity, healing, scar formation, duration of results, and
      tension-related trophic changes. Twelve fresh frozen cadavers were dissected. At
      random, one side was treated with the composite technique as described by Hamra,
      whereas the other was treated with a standard subcutaneous rhytidectomy without
      SMAS intervention. Using this approach, variability between techniques could be
      more accurately compared. Dissection levels were made as identical as possible on
      both sides. Tensions were then measured from premarked, standard key points,
      evaluating (1) the amount of tension required to move the point 2 cm; (2) with a
      pull of 1.00 kg, the amount of skin that could then be excised; and (3) after
      securing the composite 2.0 cm reference points using deep-tissue support sutures,
      the amount of tension needed to advance the skin to closure. We found that the
      composite method has a higher resistance to stretch than the subcutaneous method,
      which translates into a lesser amount of skin excision possible at a given
      tension. The added resistance is most likely the result of the deep fibromuscular
      layer. Resistance could be overcome by placement of deep support sutures, and the
      effect of the fibromuscular layer (SMAS) is effectively neutralized through
      increased viscoelastic support. This effect potentially helps to protect the
      dermal plexuses from the effects of tension created using the composite
      technique. The tension necessary to advance the epidermis to closure therefore
      compares favorably to the subcutaneous rhytidectomy method.

PMID- 8579259
TI  - Venous structures associated with thermoregulation of phocid seal reproductive
      organs.
AB  - BACKGROUND: Seal reproductive systems are surrounded by thermogenic muscle and
      insulating blubber, suggesting elevated temperatures at the gonads and uterus. In
      the limbs of terrestrial mammals, cooled blood returning from superficial veins
      is mixed proximally with warm blood returning from deep veins. Thus, mixed cool
      superficial and warm-deep venous blood from the hind limbs is returned to the
      central circulation. METHODS: We describe structures observed in salvaged
      carcasses of harbor (Phoca vitulina), gray (Haliochoerus gryphus), harp (Phoca
      groendlandica), hooded (Cystophora cristata), and ringed (Phoca hispida) seals.
      Vessels were identified by dissection of injected and uninjected material.
      RESULTS: In contrast to terrestrial mammals, phocid seals have anastomoses
      between the veins of the distal hind limb and the pelvis which allow large
      volumes of cool blood returning from the skin surface of the flipper to enter the
      gluteal, pelvic, or pudendo-epigastric veins. This provides a cool-superficial
      venous return that remains separate from the warm-deep venous return of the
      femoral veins. The cooled venous blood from the hind flippers supplies venous
      plexuses lining the inguinal region and the abdominal and pelvic cavities.
      CONCLUSIONS: Cooled blood may prevent hyperthermic insult to seal reproductive
      systems.

PMID- 8579261
TI  - Clinical significance of intracapsular fluid in patients' breast implants.
AB  - Clinical reports on the incidence and clinical significance of intracapsular
      fluid are lacking in the literature. It remains unknown whether the presence of
      intracapsular fluid has any relation to implant infection or colonization. The
      purpose of this study was to determine the frequency and type of intracapsular
      fluid, specifically, whether intracapsular fluid causes implant infection,
      implant rupture, or bacterial colonization. A total of 139 implants from 72
      symptomatic patients were entered into the prospective clinical study. Our study
      demonstrated the presence of intracapsular fluid in 21 of 139 (15%) implants.
      Positive microbial cultures were identified in 39% of the implants in the
      positive intracapsular fluid group, compared to 43% in the negative fluid group.
      There was no statistically significant difference between these groups. Also, no
      adverse clinical relationship was demonstrated between local symptoms and
      presence of intracapsular fluid. There was, however, a positive trend toward the
      presence of fluid when implant shell types were nonsmooth (polyurethane and
      textured silicone implants). Further studies are indicated to elucidate the fluid
      production mechanism and possible secretory activity of prosthetic capsules
      interfacing the textured breast implant surface.

PMID- 8579262
TI  - Postmastectomy reconstruction: comparative analysis of the psychosocial,
      functional, and cosmetic effects of transverse rectus abdominis musculocutaneous
      flap versus breast implant reconstruction.
AB  - Over 40,000 postmastectomy breast reconstructions are performed annually. In this
      study, we investigated the psychosocial, functional, and cosmetic effects of
      transverse rectus abdominis musculocutaneous (TRAM) flap versus breast implant
      reconstruction. Thirty-three women who had undergone postmastectomy breast
      reconstruction were contacted by telephone and agreed to participate in the
      study. Twenty-two women completed the self-assessment questionnaires regarding
      their quality of life, psychological symptoms, functional status, body image, and
      global satisfaction. The TRAM and implant groups contained 8 and 14 patients,
      respectively. The groups were well matched for age, employment status, marital
      status, race, religion, and severity of medical and surgical illnesses. The
      average follow-up was 36 months. Statistical analysis of the responses revealed
      that women who had undergone TRAM flap reconstruction were more satisfied with
      how their reconstructed breast felt to the touch (p = .01), and there was a trend
      toward greater satisfaction with the appearance of their reconstructed breast (p
      = .08). However, these same patients identified more difficulties as far as
      functioning at work or school, performing vigorous physical activities,
      participating in community or religious activities, visiting with relatives, and
      interacting with male friends (p < .04). There were no statistically significant
      differences in body image or overall satisfaction. In this small cohort study,
      both the TRAM flap group and the implant group were satisfied with the results of
      their breast reconstruction, but the TRAM flap group was more satisfied with how
      their breast felt and tended to be more satisfied with the cosmetic result. The
      TRAM flap group reported greater psychological, social, and physical impairments
      as a result of their reconstruction.

PMID- 8579263
TI  - Identification and management of minimally displaced nasoethmoidal orbital
      fractures.
AB  - The management of nasoethmoidal orbital injuries can be difficult. Clinical
      recognition and options for correction are diverse. Recently we treated several
      patients with limited facial injuries in which the nasoethmoidal complex
      "greensticks." Treatment with limited exposure and rigid fixation allows for
      adequate reduction. Clinical recognition and an outline for treatment of these
      limited injuries is presented.

PMID- 8579264
TI  - The radial artery perforator-based adipofascial flap for dorsal hand coverage.
AB  - The radial artery perforator-based adipofascial flap seems to be suitable for
      resurfacing defects on the dorsal hand. This flap is classified as one of the
      distally based intertendinous septocutaneous flaps, which are supplied by the
      dorsal superficial branch of the radial artery. The advantages of this flap are
      (1) surgery is minimal, of short duration, and associated with minimal donor
      scarring; (2) the perforator of the flap encompasses a wide and long territory of
      adipofascial tissue; (3) there is no postoperative functional limitation; (4)
      freedom of arm movement allows better control of postoperative edema, early
      physiotherapy, and mobilization; (5) soft-tissue coverage actively contributes to
      the vascularity of the hand; and (6) the donor forearm cutaneous veins and
      cutaneous nerves can be preserved.

PMID- 8579265
TI  - Reconstruction of the upper leg and knee with a reversed flow saphenous island
      flap based on the medial inferior genicular artery.
AB  - Soft-tissue defects around the knees and below-the-knee amputation stumps are
      difficult to reconstruct. We present an option for reconstruction of these
      defects. Reversed flow saphenous island flaps, based on the medial inferior
      genicular artery, were successfully transferred in 6 patients. All wounds healed
      well postoperatively. The donor defect can be closed directly when the width is
      less than 7 cm. This is a thin and reliable fasciocutaneous flap that is useful
      in covering defects around the knee joint, popliteal fossa, upper half of the
      leg, and below-the-knee amputation stump.

PMID- 8579266
TI  - Comparative clinical study of the sure-closure device with conventional wound
      closure techniques.
AB  - The Sure-Closure device, designed for wound closure, harnesses the viscoelastic
      properties of the skin. It has been used in clinical studies in the past. We have
      evaluated the role of this device in complex wound problems and compared it to
      closure achieved by conventional wound closure methods such as skin grafts and
      flaps. A total of 40 patients with multiple wound etiologies were examined. We
      used the device under local and general anesthesia. In addition, we performed
      cost analysis on the use of the device and compared this to traditional methods.
      We found a cost reduction trend associated with the Sure-Closure method (p <
      .05). All of the 24 patients in whom the device was used to close the wounds had
      complete primary closure. The device is also easy to use. When used for delayed
      stretching, as in some of our patients, the compliance rate was high.

PMID- 8579267
TI  - Bilateral gluteus maximus V-Y advancement musculocutaneous flaps for the coverage
      of large sacral pressure sores: revisit and refinement.
AB  - Surgical management of the sacral defect using the gluteal muscle or
      musculocutaneous flap has been well accepted over the years. In this study,
      refinements in the bilateral gluteus maximus V-Y advancement musculocutaneous
      flaps were made. These refinements include having sharper angle (60 degrees or
      less) at the donor sites of the flap, cutting the edges of the gluteal muscle of
      3 cm beyond the skin flap, and cutting most parts of the gluteal muscle at a
      depth of only 2.5 cm (at the level of upper third portion). These improvements
      result in less tension closure of the donor site, easier closure of the advanced
      flaps in two planes without tension, and better preservation of most parts of the
      gluteal muscular insertions to the femur and their functions. The design of V-Y
      advancement has successfully maintained the superior and inferior gluteal vessels
      and inferior gluteal nerve. In this study, the average sacral defect was more
      than 12 cm in diameter, and each advanced flap was 15 x 12 x 3 cm in size. Of the
      63 consecutive patients undergoing bilateral gluteus maximus V-Y advancement
      musculocutaneous flaps with refinements for coverage of large sacral pressure
      sores, 59 (93%) achieved complete healing after an average follow-up period of 28
      months. Only 4 patients had recurrences of sacral sore. In this study, the
      duration of hospital stay for flap coverage averaged 38.5 days. Four patients
      (6%) had superficial dehiscences of the donor site requiring skin grafting. Ten
      patients (16%) developed stitch abscesses and 9 patients (14%) had wound
      infections, but no flap was lost. No significant functional impairment related to
      the flap procedure was noted. The operative technique described in this paper is
      not only simple and noninvasive, but with our refinements of flap design, the
      bilateral gluteus maximus V-Y advancement musculocutaneous flaps also provide
      reliable and durable coverage for large sacral pressure sores.

PMID- 8579268
TI  - The potential of oral mucosal cells for cultured epithelium: a preliminary
      report.
AB  - We have developed a method to fabricate cultured epithelium for skin repair using
      mucosal cells. We grafted this epithelium in six cases. The site where the
      mucosal epithelium was transplanted keratinized normally within 4 weeks and
      formed normal skin. Mucosal epithelial cells have many advantages over skin
      epidermal keratinocytes: (1) Mucosal epithelial cells grow faster than skin
      keratinocytes. (2) Cultured epithelial sheets formed using mucosal cells remain
      viable for at least 14 days in vitro. (3) The oral cavity is a suitable location
      to take a tissue segment because scar due to biopsy is inconspicuous. Therefore,
      mucosal epithelial cells are a potential new source of cells for cultured
      epithelial graft.

PMID- 8579269
TI  - Debilitating silicone granuloma of the penis and scrotum.
AB  - The restoration and improvement of body contour have intrigued surgeons for over
      100 years, generating much interest in the subcutaneous/intradermal injection of
      highly viscous fluids. The local complications of liquid silicone injection have
      been well documented over the past 30 years. Although Dow-Corning has not made
      medical-grade liquid silicone available for use in humans without an approved
      research application since 1966, practitioners, both licensed and unlicensed,
      have administered these injections worldwide for a variety of indications
      throughout the body. There is little or no information concerning the
      adulteration of these injectates. To date, there have been four case reports of
      penile injections--the indications being evenly split between the treatment of
      impotence/sexual inadequacy and augmentation. The most recent description was
      published in 1982. We present a case of debilitating silicone granuloma of the
      penis and scrotum secondary to large-volume injections into the corpora
      cavernosae and penile soft tissues administered in Belgium 14 years prior to
      presentation. The development of a silicone foreign body reaction, massive edema,
      and subsequent impotence lends itself to a clinical diagnosis and aggressive
      treatment with wide local excision and appropriate soft-tissue coverage. The
      metabolic fate of silicone in vivo remains inadequately characterized and a
      fertile area for research as new methods involving nuclear magnetic resonance
      spectroscopy have been devised to identify silicone and highly coordinated
      silicone complexes.

PMID- 8579270
TI  - Transverse rectus abdominis musculocutaneous flap breast reconstruction in sickle
      cell disease.
AB  - Patients with homozygous sickle cell disease pose an enormous challenge to the
      reconstructive surgeon. Historically, the risk of attempting flap reconstruction
      was considered prohibitive. A successful case of immediate breast reconstruction
      with a "supercharged" bipedicled transverse rectus abdominis musculocutaneous
      flap is presented. Perioperative transfusions that maintained the sickle
      hemoglobin S level below 30% were crucial in preventing erythrocyte sickling in
      the microcirculation of the flap during the period of relative ischemia.

PMID- 8579271
TI  - Desmoid tumor occurring after reconstruction mammaplasty for breast carcinoma.
AB  - We present a case of desmoid tumor associated with prior alloplastic breast
      reconstruction. Wide local excision that includes chest wall resection, if
      necessary, is the primary treatment of choice. Patients with extensive
      nonresectable or recurrent disease may benefit from radiation therapy. Systemic
      therapy is a possibility in certain cases, but its toxicity generally precludes
      its use with this nonmetastatic tumor. Although this is the fourth reported case
      of desmoid tumor arising after implantation of a silicone prosthesis, we cannot
      claim a causal relationship. Careful follow-up consisting of yearly physical and
      mammagraphic examinations may facilitate early diagnosis and treatment of locally
      aggressive desmoid tumors but is not warranted, except in the context of routine
      screening for breast carcinoma.

PMID- 8579272
TI  - Thigh augmentation.
AB  - Based on the experience with calf and buttock augmentation, a new type of implant
      was designed for thigh augmentation. A case report is presented.

PMID- 8579273
TI  - Large nasal tip teratoma.
AB  - Congenital teratoma rarely occurs in the craniofacial region. We present an
      infant with a nasal tip teratoma that was documented by ultrasonographic
      examination. The tumor was excised at 1 day of life, and the splayed upper and
      lower lateral cartilages were apposed primarily. The remaining redundant skin was
      excised in a second stage. To our knowledge, this is the first reported case of a
      nasal tip teratoma.

PMID- 8579274
TI  - Lemierre's syndrome: a case of postanginal septicemia and bilateral flank
      abscesses.
AB  - Lemierre's syndrome is characterized by pharyngeal infections in young healthy
      adults with secondary septic thrombophlebitis and multiple metastatic infections.
      In the preantibiotic era, Lemierre's syndrome was common and lethal. With the
      advent of antibiotics, Lemierre's syndrome has become such a rare entity that the
      diagnosis is often delayed or missed. With prompt recognition, appropriate
      antibiotic therapy, and surgical drainage of metastatic abscesses, the majority
      of patients can be cured. A case of Lemierre's syndrome in a 22-year-old
      previously healthy man treated on a plastic surgery service is presented.
      Surgeons who can be consulted for deep space infections should be aware of this
      disease so that the diagnosis and treatment can be initiated promptly to prevent
      patients from succumbing to this life-threatening but curable disease.

PMID- 8579275
TI  - Reconstruction of the totally degloved little finger with a bilobed digital
      neurovascular island flap.
AB  - Treatment of a completely degloved finger injury is a challenge to plastic
      surgeons. We used a simple method, a bilobed digital neurovascular island flap
      harvested from the dorsolateral side of the middle and proximal phalanges of the
      ring finger, to reconstruct the complete degloved little finger. This method
      provides a one-stage operation for coverage of the degloved little finger and
      also results in good sensation and an acceptable appearance.

PMID- 8579276
TI  - Entrapment of the palmar cutaneous branch of the median nerve by a normal
      palmaris longus tendon.
AB  - An anomalous course of the palmar cutaneous branch of the median nerve was noted
      in a patient with symptoms of compression of the median nerve and its palmar
      cutaneous branch at the wrist level. The palmar cutaneous branch of the nerve
      pierced the tendon of a normal palmaris longus muscle near its insertion.
      Decompression of the median nerve and its palmar cutaneous branch was performed,
      with complete relief of symptoms.

PMID- 8579277
TI  - "Metastatic breast carcinoma" that is neither metastatic nor breast.
AB  - Histologically, primary sweat gland neoplasms can mimic metastatic breast
      adenocarcinoma. The clinical history of a chronic, solitary nodule helps in
      distinguishing these two tumors. Understanding the differential diagnosis is
      essential in managing nodular skin tumors.

PMID- 8579278
TI  - Cutaneous pseudolymphoma: an unusual presentation of a deep subcutaneous thigh
      mass.
AB  - Cutaneous pseudolymphoma is considered to be a benign (reactive) cutaneous
      lymphoid infiltrate; the term designates reactive diseases of the skin that
      histologically mimic cutaneous lymphoma. We report a case in which a 63-year-old
      female presented with a 5-month history of a progressive skin eruption and an
      enlarging subcutaneous mass following a presumed insect bite. Excisional biopsy
      showed this to be a pseudolymphoma extending from the dermis into the
      subcutaneous tissue. A number of pathological features that distinguish
      pseudolymphoma from cutaneous lymphoma, including histology, immunophenotype, and
      immunogenotype, are reviewed. The case herein challenges previous beliefs that
      pseudolymphoma is confined to cutaneous involvement and indicates that the
      process can involve deeper tissues. The final criterion for distinguishing benign
      from reactive processes is biological behavior. Since the depth of invasion in
      cutaneous pseudolymphoma has not previously been appreciated, the patient will
      need to be carefully examined periodically until the biological behavior of the
      process has been determined.

PMID- 8579279
TI  - Basal cell carcinoma in black patients: the need to include it in the
      differential diagnosis.
AB  - We present a retrospective study of 276 basal cell carcinomas which we have
      identified 5 (1.8%) black patients. This finding agrees with the current
      literature, which states that basal cell carcinoma in the black population is
      relatively infrequent. Although basal cell carcinoma in black patients is
      uncommon, it should be included in the differential diagnosis of any suspicious
      lesion in this population to avoid the morbidity that is associated with a delay
      in diagnosis. In this study we also present the possible association of basal
      cell carcinoma occurring concomitantly with a second primary malignancy in this
      population. In black patients basal cell carcinoma is found more frequently in
      regions of the body that are protected from ultraviolet radiation when compared
      to white patients. This leads to the speculation that a different pathogenesis of
      basal cell carcinoma exists for black patients.

PMID- 8579281
TI  - The promise of Aladdin.

PMID- 8579280
TI  - Cytokines: a primer for plastic surgeons.
AB  - Cytokines are peptide mediators of inflammation that are being extensively
      studied in several aspects of disease. I provide an introduction to the general
      features of cytokine biology. Cytokines may be considered as either
      proinflammatory or anti-inflammatory compounds, and they also have potent
      hematopoietic effects. Basic information about the biological properties of the
      cytokines and their receptors and mechanisms of postreceptor signal transduction
      is presented. Lymphocytes have been subclassified into specific cell types, and
      the Th1 and Th2 classifications are discussed. Cytokines are administered
      exogenously to augment aspects of the immune response; this approach has been
      particularily well established for the hematopoietic growth factors. In other
      diseases, inhibition of cytokines has been attempted by several approaches,
      including monoclonal antibodies, soluble receptors, and receptor antagonists.
      Finally, the general methods of measuring cytokines and the advantages/pitfalls
      associated with these methods are reviewed.

PMID- 8579282
TI  - Testing for haemochromatosis in the diabetic clinic.
AB  - Random serum transferrin saturation (TS) was measured in 1194 patients attending
      a diabetic clinic. Twenty-one patients had TS > 55% and in three of these
      patients repeat random TS was < 55%. Seventeen patients were recalled for fasting
      serum TS and ferritin measurement. Ten patients had fasting TS > 55%. The
      diagnosis of haemochromatosis was confirmed by liver biopsy in a total of six
      patients, three of whom were previously unsuspected. Haemochromatosis was the
      possible diagnosis in a further four patients. Family studies using HLA typing
      confirmed haemochromatosis in four family members, three of whom were
      asymptomatic. We conclude that measurement of TS is a simple and effective method
      of finding cases of haemochromatosis in the diabetic clinic.

PMID- 8579283
TI  - Assessment of iron status in association with excess alcohol consumption.
AB  - Biochemical evidence of iron overload (transferrin saturation greater than 60%
      and/or serum ferritin concentration greater than 1000 micrograms/L) was observed
      in 16% of patients admitted to an alcohol withdrawal unit. No subjects in an age
      and sex matched control group showed such biochemical changes. Whilst changes in
      serum ferritin concentration closely correlated with aspartate aminotransferase
      activity and could be explained by alcohol induced liver damage, the increased
      transferrin saturation was not similarly explained. In nine patients withdrawal
      of alcohol resulted in a decrease in transferrin saturation and serum ferritin,
      the former due to a reduction in serum iron concentration. In patients with high
      alcohol intake biochemical measures of iron status may be misleading and a
      decrease in both transferrin saturation and serum ferritin concentration after
      withdrawal of alcohol may help to rule out the possible diagnosis of hereditary
      haemochromatosis.

PMID- 8579284
TI  - Influence of race, age and sex on the lymphocyte subsets in peripheral blood of
      healthy Malaysian adults.
AB  - The lymphocyte subsets in the peripheral blood of healthy Malaysian adults (212
      subjects, age 18-71 years) were analysed using a flow cytometer FACScan in an
      effort to establish a reference range for the lymphocyte subsets. The lymphocyte
      subsets studied were T cells (CD3), B cells (CD19), natural killer (NK) cells
      (CD3- CD16+/CD56+), helper/inducer cells (CD4), cytotoxic/suppressor cells (CD8)
      and the helper/suppressor ratio (CD4/CD8). The distributions of T cells, CD4
      cells and CD8 cells were symmetric about their means while B cells, NK cells and
      CD4/CD8 ratio followed a skewed distribution. Differences in race were observed
      for T cells, NK cells, CD4 cells and CD4/CD8 ratio where the Indians were
      significantly different from the Malays and the Chinese (higher T cells, CD4
      cells and CD4/CD8 ratio and lower NK cells). The B cells were significantly lower
      in the Chinese than the Malays and the Indians. Age differences were seen only in
      the Chinese where increased CD4 cells and CD4/CD8 ratio, and decreased CD8 cells
      were observed. A sex difference was observed only in the Chinese where the
      CD4/CD8 ratio was significantly higher in females than males.

PMID- 8579285
TI  - External quality assessment of techniques for assay of serum ethanol.
AB  - Ethanol was assayed by an average of 200 participants in the UK National External
      Quality Assessment Scheme, in 26 samples of human serum containing 0.1%
      fluoride/oxalate and added ethanol from 0.2 to 4.5 g/L. Outliers greater than
      three standard deviations from the consensus mean for any sample were excluded.
      Data remaining were grouped by technique and the technique mean and standard
      deviation calculated. Inter-laboratory variation of 13 technique groups was
      assessed by the coefficient of variation of measurements and bias from the per
      cent difference of the technique mean from the target value. Gas chromatography
      (GC) with packed columns and Sigma alcohol dehydrogenase assay protocols that
      include a sample deproteinization step, showed better between-laboratory
      agreement but greater bias. The least variable techniques were headspace analysis
      with GC-packed columns, Kodak Ektachem, bioMerieux and DuPont aca assays. A
      significant negative bias was produced by Kodak Ektachem and a positive bias by
      the Lion alcometer which was the most variable technique.

PMID- 8579286
TI  - Relationship between a mild alpha 1 proteinase inhibitor deficiency and
      respiratory symptoms in a family.
AB  - A 34-year-old man with pulmonary emphysema was found to have a mild alpha 1
      proteinase inhibitor (alpha 1 PI) deficiency. alpha 1 PI status was investigated
      in this patient and in 35 members of his family. The alpha 1 PI investigations
      included alpha 1 PI concentration and phenotype and serum inhibitory capacity for
      trypsin and pancreatic elastase. Fifteen members of the family had alpha 1 PI
      concentration and inhibitory capacities below the lower normal limit. Five of
      these members were characterized by the heterozygous MP phenotype and the 10
      others by an apparently homozygous M phenotype, in which the M allele may be
      associated with another unidentified deficiency allele. Two members of the family
      had alpha 1 PI concentration and elastase inhibitory capacity below the lower
      normal limits and trypsin inhibitory capacity within the normal range. They were
      both characterized by the MP phenotype. Six of these 17 members (three of PI type
      M and three of PI type MP) showed chronic pulmonary symptoms, whereas among the
      19 alpha 1 PI non deficient members, no member had a history of significant
      pulmonary symptoms.

PMID- 8579287
TI  - Determination of total and herpes simplex virus specific monomeric and dimeric
      IgA in serum and cerebrospinal fluid by ultracentrifugation.
AB  - An improved method is described for differentiating between monomeric and dimeric
      total and herpes simplex virus (HSV) specific IgA by ultracentrifugation in
      sucrose gradient, using recovery and quantitative analysis of the fractions
      obtained. Calculation of monomeric and dimeric IgA was based on IgG as an
      internal standard. Intrathecally produced monomeric and dimeric IgA were judged
      by calculating IgA indices for each form. A new type of formula indicating
      relative over-production of dimeric compared with monomeric IgG (IgA dimeric
      monomeric index) is suggested. The method was applied to serum and cerebrospinal
      fluid (CSF) from three patients with HSV encephalitis. The index for monomeric as
      well as dimeric IgA was high during the acute phase of the disease, indicating
      intrathecal synthesis of both molecular forms. One year after onset, there was no
      detectable HSV-specific IgA in CSF: both molecular forms, however, remained in
      serum. The amount of dimeric compared with monomeric IgA was high during the
      acute phase, and subsequently decreased after successful treatment. A new finding
      was the detection of HSV-specific IgA heavier than dimeric IgA in serum one year
      after onset of the disease. These components may be tetrameric IgA, or immune
      complexes containing IgA.

PMID- 8579288
TI  - Urinary heparan sulphate proteoglycan excretion is abnormal in insulin dependent
      diabetes.
AB  - Urinary excretion of heparan sulphate proteoglycan (HSPG), the main anionic
      component of the glomerular basement membrane (GBM), was estimated in 30
      adolescents and young adults with insulin dependent diabetes (IDDM), 10 with
      microalbuminuria and 20 sex matched, diabetic controls of similar age without
      evidence of microalbuminuria. A further 10 non-diabetic control subjects were
      also examined. Both groups of patients with diabetes had significantly elevated
      excretion of HSPG when compared to normal individuals. There was no difference in
      HSPG excretion between diabetic subjects with and without microalbuminuria.

PMID- 8579289
TI  - A new enzymatic method for the determination of inulin.
AB  - A new enzymatic method for the determination of inulin in plasma and urine, using
      inulase (EC 3.2.1.7), fructokinase (EC 2.7.1.4), phosphoglucoisomerase (EC
      5.3.1.9) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49) is described. The
      assay is based on the hydrolysis of inulin or Inutest (INutest which is the
      injectable form of inulin), by inulase and the determination of fructose
      released. The assay was linear up to 2 g/L of Inutest. The within-batch and
      between batch coefficients of variation were 2.3% and 2.2%, respectively.
      Recovery of added Inutest from plasma and urine was 98-102%. There was no
      interference from glucose (27.7 mmol/L), fructose (1.7 mmol/L) or mannose (1.7
      mmol/L). When inulin clearance (using this method) and thiosulphate clearance
      were compared in 37 patients the inulin clearance was 9.3 mL/min (12%) lower than
      the thiosulphate clearance. We conclude that this enzymatic method is a simple
      and specific method.

PMID- 8579290
TI  - Serum binding of steroid tracers and its possible effects on direct steroid
      immunoassay.
AB  - We studied the serum protein binding of 3H-labelled progesterone, oestradiol and
      testosterone, and five 125I-labelled analogues of these steroids. All tracers
      investigated appeared to be bound by proteins in every serum sample tested. The
      addition of blocking agents caused a substantial reduction in serum protein
      binding of 3H-labelled steroids, but had relatively little effect on the binding
      of analogue steroid tracers. Use of analogue steroid tracers in conventional
      direct immunoassays for oestradiol and progesterone produced anomalous results
      for some patient samples when compared to extraction radioimmunoassays, but
      assays where tracer binding to serum constituents was prevented by adoption of
      two-step procedures appeared to avoid anomalous results. The results suggest that
      serum protein binding of steroid analogue tracers may be a source of interference
      in some direct steroid immunoassays.

PMID- 8579291
TI  - Evaluation of an enzyme-immunometric assay for serum alpha-glutathione S
      transferase.
AB  - A commercially available enzyme-immunometric assay for serum alpha-glutathione S
      transferase (GST) was evaluated. Endogenous serum alpha-GST diluted linearly
      within the calibration range. However, we recommend that the sample and second
      antibody reagent are always added sequentially in the assay to avoid hook effect.
      Between-assay variability was below 7% across the calibration range and the upper
      limit of the reference range in adults (n = 219) was 11.4 micrograms/L. Within
      individual variability in serum alpha-GST concentrations measured over a 4-6 week
      period in 4 healthy adults was small. Serum alpha-GST concentrations did not
      change significantly 6 h after a therapeutic dose of paracetamol. Studies in two
      patients after liver transplantation showed that serum alpha-GST is a better
      discriminant of acute changes in liver function than conventional tests. Serum
      alpha-GST concentrations were unaffected by gross muscle damage, extrahepatic
      inflammation, or haemolysis and thus appear to be more liver specific than
      transaminase activities. The effect of renal impairment on serum alpha-GST
      concentrations requires further investigation.

PMID- 8579292
TI  - Routine therapeutic monitoring of lamotrigine in epileptic patients using a
      simple and rapid high performance liquid chromatographic technique.
AB  - We have developed a simple and rapid high performance liquid chromatographic
      technique to determine lamotrigine concentrations in epileptic patients and
      validated it using external quality control material. The method has been used to
      monitor the lamotrigine concentration in 70 specimens from 61 patients. Only 50%
      of the specimens had concentrations within the proposed target range of 1 mg/L to
      4 mg/L, and there was no relationship between lamotrigine concentration and age,
      sex, other anti-epileptic treatments, or dose, although this could in part be
      explained by concomitant anti-epileptic therapy. We suggest that lamotrigine
      should be monitored therapeutically in order to assess its efficacy and audit its
      use as an anti-epileptic treatment, especially with the introduction of this
      relatively new drug as monotherapy.

PMID- 8579293
TI  - Twelve months' experience of a quality assessment scheme for urine tests using
      reagent strips.

PMID- 8579294
TI  - 25(OH)-vitamin D assay in plasma: experience in using a commercial kit assay for
      survey work.

PMID- 8579295
TI  - Hyporeninaemic hypoaldosteronism and systemic amyloidosis.

PMID- 8579296
TI  - Amino acid data processing.

PMID- 8579297
TI  - Phaeochromocytoma diagnosis.

PMID- 8579298
TI  - [1984-1994: Ten years of skin flaps. Foreword].

PMID- 8579299
TI  - [History and prehistory of skin flaps].

PMID- 8579300
TI  - [1984-1994: ten years of skin flaps. Improvements and conceptual developments.
      Development of vascular concepts, classification and clinical concepts].
AB  - After a brief review of definitions and semantics, the author recalls the state
      of the art before 1984 concerning arterial and venous cutaneous blood supply.
      Studies and concepts published since 1984 include those of Nakajima, who
      distinguished six types of cutaneous arteries, Gumener, who emphasized the
      vascular entity represented by the subcutaneous connective tissue, and Taylor.
      This author, after many studies on the whole body, defined forty arterial and
      venous cutaneous territories, border-arteries and veins oscillating at the
      borders of these territories, as well as a number of neurovascular entities
      (neurocutaneous arteries and veins). In terms of haemodynamics, the concepts of
      anatomical, haemodynamic and potential arterial cutaneous territories, the
      concepts of arteriosome and venotome and the concept of low venous pressure zones
      are analysed. These anatomical and concepts haemodynamic are the basis for the
      feasibility and reliability of the various cutaneous, musculocutaneous and
      fasciocutaneous flaps. A number of classifications for these various flaps have
      been proposed since 1984: a theoretical classification (Kunert's),
      classifications according to vascular systematization, including Nakajima's
      classification, and many others. The author proposes a practical classification
      which should allow a better understanding and better national and international
      exchange. In parallel, the design and indications of various types of flaps have
      also advanced since 1984. Skin flaps without a systematized blood supply do not
      correspond to random flaps. Musculocutaneous flaps have advanced in three
      directions: partial muscular harvesting when the objective of the flap is
      essentially cover, an increase of the skin flap surface area; substitution, in
      certain anatomical regions, of the concept of fasciocutaneous flap for that of
      musculocutaneous flap, particularly in thoracolumbar and anterior thoracic
      regions. The author notes the progress in fasciocutaneous flaps: distal pedicle
      leg flaps, development of decreased cutaneous morbidity resulting in
      fasciosubcutaneous flaps and proximal or distal fascial (or fascio-adipose)
      pedicle fasciocutaneous island flaps, progress of normal flow or reverse flow
      island septocutaneous flaps on the main vessels of the limbs towards to similar
      types of island flaps on secondary vessels, especially in peri-articular sites.
      The other clinical concepts analysed include grafted fascial flaps, grafted
      adipose and fascioadipose flaps, neurocutaneous flaps, "tailormade" flaps and
      chimeric flaps. This progress in vascular and clinical concepts of skin cover
      flaps over the last ten years is illustrated by many examples of skin cover,
      particularly involving the posterior aspect of the heel.

PMID- 8579301
TI  - [1984-1994: Ten years of skin flaps. Development of transfer techniques. New
      methods of autoplasty described during this period].
AB  - Ten years of flaps represent a little and a lot. It is little compared to the
      2600 years since the first flap in plastic surgery: the Susruta Indian flap, but
      it is a lot in view of the phenomenal acceleration of this speciality since the
      Second World War. In 1994 alone, more than two hundred references are listed
      under the heading "new flaps". As it is impossible to be exhaustive, the author
      has chosen to focus on two main aspects: a theoretical review of new transfer
      techniques, dealing successively with: the principles of reverse flow flaps,
      venous flaps, neurocutaneous flaps, so-called "extracorporeal" transfers, reverse
      flow YV technique; and practical aspects based on a review of eighteen
      autoplasties or donor sites selected for their surgical value, their
      reproductibility and their innovative nature. The author's objective is not to
      present a technical treatise, but rather to make the reader aware of several key
      points or even, in some cases, the very existence of these autoplasties. This
      paper is designed to be didactic, with extensive references, in order to act as a
      practical guide. It also demonstrates, as if there were any need, to what extent
      plastic surgery is able to create new solutions and the essential value of
      continuing research.

PMID- 8579302
TI  - [1984-1994: Ten years of skin flaps. Recent advances in experimental surgery].
AB  - The author has selected and updated four subjects in Plastic Surgery research.
      All flap monitoring procedures are detailed. They are still insufficient, as none
      of them can be used in all clinical situations. Free radicals have been
      implicated in the extension of necrosis after reperfusion of an ischaemic flap.
      Many substances have been tested for their scavenger action, particularly
      superoxide dismutase. Continuous intraarterial infusion of fibrinolytics is the
      treatment of the "no reflow phenomenon". A protocol with urokinasis, lidocaine
      and enoxaparine for ten days is used in our department with a 75% success rate.
      Finally, many interesting advances have been made to improve the biotolerance of
      allogeneic transfers. Cryopreservation of transplanted tissues at -196 degrees C
      for three weeks seems to be an interesting solution to avoid the rejection
      phenomenon.

PMID- 8579304
TI  - Sexual function and dysfunction.

PMID- 8579303
TI  - [1984-1994: Ten years of skin flaps. Prefabricated flaps].
AB  - The term prefabrication of flaps corresponds to completely different technical
      modalities, often complementary and associated, which share the common feature of
      extending the indications and potential of pedicle or free flaps. Current methods
      of prefabrication of flaps can be considered to be based on one or several basic
      principles of reconstructive surgery. The authors discuss and analyse various
      modalities: a free flap can be made autonomous or can be expanded prior to
      transfer. A transfer can be initially prefabricated at its donor site by
      performing several operative steps in situ. A free transfer can be performed on
      the main vascular axis of a flap which is subsequently transferred, for example:
      free scalp transfer to reconstruct an eyebrow on a donor site reconstructing half
      of the face, but the first in situ operative phase usually consists of performing
      cutaneous, bone, cartilaginous or even alloplastic material transplants. The
      transfer is only performed after a sufficiently satisfactory complex anatomical,
      functional or esthetic unit has been achieved, in order to avoid difficult or
      dangerous remodeling operations after transfer. The most revolutionary appearance
      in the area of prefabrications is certainly induction of a pedicle or free
      neoflap in a so-called random territory. The addition of an arteriovenous pedicle
      associated with fascia underneath a muscle, underneath a skin cover, in contact
      with an osteoperiosteal segment allows a perfectly transferable neovascularized
      unit to be obtained after several weeks. All of the procedures described:
      autonomization before transfer, expansion before transfer, in situ prefabrication
      of a complex unit by addition of several tissue units (autologous or alloplastic)
      in one or several stages and finally vascular induction of a muscular, cutaneous
      or bone unit, etc. by transfer of a vascular axis in contact with this anatomical
      structure and combinations of these various modalities obviously open up a new
      approach which will considerably extend the already remarkable possibilities
      offered by free tissue transfers.

PMID- 8579305
TI  - Sexuality of women after mastectomy.
AB  - Changes in sexual functioning, attitudes and sexual behaviour in local women
      after mastectomy and conservative breast surgery for breast cancer were assessed
      in this study. Given the social bearing, only married women agreed to be entered
      into the study. The complexities of variables other than breast loss,
      contributing to sexual difficulties were recognized and assessed. Through
      questionnaires designed for local women, a significant proportion of mastectomy
      women were found to have disturbances in at least one area in their sexual
      functioning after surgery. A significant number experienced changes in their
      sexual habits as well.

PMID- 8579306
TI  - Follow-up study of female transsexuals.
AB  - The aim of this study was to examine the social and sexual adjustments of
      Singapore female transsexuals following sex reassignment surgery. All female
      transsexuals who were operated on since 1989 were interviewed. There were a total
      of 17 transsexuals with a mean age of 29 years (range, 20 to 41 years) at the
      time of inception. Before surgery, all were single. After surgery, 6 out of 11
      subjects had married abroad. Before surgery, some had problems with identity
      cards, passports, travelling and work which were resolved with surgery. They were
      better accepted and had better sexual adjustment after surgery. All were
      satisfied with the change in sex, but only 65% were satisfied with the surgery.
      Only 59% said they were willing to undergo the operation again. After a test case
      in court, they were unable to marry in Singapore. Their primary motive to undergo
      sex reassignment surgery was to become a member of the opposite sex, so that they
      could be recognised socially and legally.

PMID- 8579307
TI  - Treating premature ejaculation in the multi-modal therapeutic framework: a single
      case study.
AB  - Generally, premature ejaculation is caused by organic, psychological,
      interpersonal factors and lay beliefs. It is defined as a lack of adequate
      voluntary ejaculatory control with the result that a patient climaxes
      involuntarily. An ejaculatory control may be said to be established when the
      patient can tolerate high levels of excitement which characterise the plateau
      stage of the sexual response cycle without ejaculating reflexly. The most
      effective treatment for premature ejaculation so far is the stop-start exercises
      that aim to help patients tolerate a prolonged period of intense pleasurable
      arousal and to enjoy sexual sensation before ejaculation. However, the stop-start
      exercises would be more effective if they are employed in a multi-modal
      therapeutic framework. This is because cases of premature ejaculation differ in
      terms of the aetiology, pathological patterns, and the patients' personal
      characteristics and background. A case is presented to illustrate how the
      conventional stop-start exercises are prescribed in this multi-modal framework.

PMID- 8579308
TI  - Sexuality of women with carcinoma of the cervix.
AB  - Interviews regarding sexual function were conducted with patients suffering from
      cervical cancer and who were previously sexually active. Eighty-Seven patients
      who were treated surgically were compared with 40 patients who had radiotherapy.
      Both groups had reduced sexual activity and decreased sexual enjoyment although
      the post-radiotherapy group fared worse. Reasons for not having sexual relations
      were explored and most cited decreased libido and poor physical condition rather
      than fear of cancer transmission through sexual activity.

PMID- 8579309
TI  - How sexually permissive are Singaporeans?
AB  - This paper presents data on two surveys done in 1989 and 1992 that indicated the
      attitudes of Singaporeans to sexuality. Both surveys revealed that Singaporeans
      have sexually conservative attitudes and those who have a lower education, are
      single, above the age of 40, are Malays/Muslims hold more conservative views.

PMID- 8579310
TI  - Sexual behaviour of male inmates of a detention facility in Singapore: risks of
      intraprison human immunodeficiency virus transmission.
AB  - Sexual urges and needs do not cease merely upon the incarceration of an
      individual. They continue to exist in varying degrees in different individuals.
      This study looks into the sexual behaviour of all the male inmates of a detention
      facility in Singapore, both before and during their incarceration. In the advent
      of acquired immune deficiency syndrome (AIDS), high risk behaviours are
      investigated with the view to applying the results towards the formulation of
      policies on prevention of intraprison transmission of human immunodeficiency
      virus (HIV). Taking masturbation as an expression of the degree of sexual needs,
      the three high risk groups for HIV infection--the promiscuous heterosexuals, the
      homosexuals/bisexuals and the intravenous drug users--had higher in-detention
      masturbation rates than the others. In addition, those incarcerated for 180 to
      360 days up to the day of the study had higher masturbation rates than those
      incarcerated for less than 180 days and longer than 360 days. In-detention
      homosexual behaviour was also demonstrated in this study. Recommendations include
      health education programmes on AIDS and risk reduction and removal of the
      prohibition on masturbation. Mandatory HIV testing and segregation of high risk
      or HIV-positive inmates are not recommended.

PMID- 8579311
TI  - Incest and other intrafamilial sexual abuse.
AB  - This study describes eight female adolescents who were sexually abused in
      childhood. Four were victims of incest. The mean age of onset of sexual abuse was
      9.8 years and except for one, all had multiple incidents. All were from the lower
      socioeconomic class. The majority had disorganised families. The reactions of the
      majority of the victims were fear, intense anger and self mutilation. All were
      separated from their families on disclosure of the abuse. A significant clinical
      sequela was that of suicidal tendency in all of them, six of whom attempted
      suicide repeatedly. Promiscuous behaviour at adolescence occurred in one victim
      of father-child incest. Lesbianism resulted in one other. None suffered from any
      formal psychiatric disorder.

PMID- 8579312
TI  - Sex education and sexual behaviour of adolescents in Japan.
AB  - In Japan sex education has been introduced into the general curriculum of primary
      schools since 1992. But due to the lack of cooperation between schools and health
      organisations, it cannot always be said that an effective and proper sex
      education has been given to students. According to the nationwide survey of the
      Japan Association on Sex Education on the sexual behaviour of students, the rate
      of students having had sexual experiences has risen for both boys and girls. As a
      result of the remarkable increase of teenage induced abortions since 1975, the
      Japan Family Planning Association started a programme for adolescent health
      issues in 1980, and the Ministry of Health and Welfare set up a project in 1981,
      which included counseling for adolescents over telephone or in person. In 1991
      another project, called the "Infant Association Learning Experience" was
      initiated as well as peer education by trained nurse students with collaboration
      between educational and health organisations in order to promote sex education;
      this had the close cooperation of families, schools and health organisations in
      the community.

PMID- 8579313
TI  - A randomised single institution study comparing laser prostatectomy and
      transurethral resection of the prostate.
AB  - We concluded a prospective randomised study comparing conventional electrocautery
      transurethral resection of the prostate (TURP) to laser prostatectomy using a
      right-angled Nd:YAG beam reflector. Seventy-one patients were evaluable, 34 laser
      and 37 TURP. Fifty patients have completed 6 months of follow-up. Using standard
      post prostatectomy outcome parameters of maximum flow rate and post void residual
      urine, laser prostatectomy shows equivalence at 6 months, with mean maximum flow
      rates of 8.76 ml/sec preoperatively improving to 15.47 ml/sec at 6 months, whilst
      for TURP patients, flow rates improved from a mean of 9.48 ml/sec preoperatively
      to 19.1 ml/sec at 6 months. Symptom scores remain higher for the laser patients
      at this time with a mean score of 9.27 compared to 4.43 for TURP patients.
      However, morbidity in the laser group is less, particularly given the absence of
      postoperative bleeding and the necessity for blood transfusion.

PMID- 8579314
TI  - A prospective trial with vacuum-assisted erection devices.
AB  - The effectiveness of vacuum-assisted erection devices was evaluated in a
      prospective trial involving 18 men with erectile dysfunction. The patients were
      reviewed at 1, 3 and 6 monthly intervals by the same interviewer using a standard
      questionnaire. Sixteen patients (88.9%) were able to attain satisfactory
      erections. The overall satisfaction rate was 83.3%. Sixteen patients (88.9%)
      found the device easy to use. Thirteen patients (72.2%) were able to master using
      the device in less than one week, and 11 patients (61.1%) were able to get it
      working at the first attempt.

PMID- 8579315
TI  - Corporeal plication for correction of penile curvature.
AB  - A retrospective analysis was done on 15 men who underwent corrective surgery for
      penile curvature between December 1989 to March 1993. The period of follow-up
      ranged from 3 months to 3 years, with a mean of 16 months. All patients underwent
      corporeal plication, with sutures placed on the convex side of the penile
      curvature to straighten the penis. Three patients (20%) developed recurrence of
      their penile curvatures between 3 months to 1 year after their surgery. All 3
      patients underwent a repeat operation. Thirteen patients (86.6%) were satisfied
      with the operation, and had a straight erect penis which did not cause pain or
      discomfort during sexual intercourse. One patient (6.7%) was particularly upset
      with a shortened penis. The last patient (6.7%) developed venous leak impotence,
      and subsequently underwent ligation and stripping of the deep dorsal vein of his
      penis.

PMID- 8579316
TI  - Penile implant surgery--local experience with the semi-rigid, single component
      inflatable and the multi-component inflatable penile prostheses.
AB  - A retrospective analysis was performed on 26 men who underwent penile implant
      surgery using semi-rigid, single component inflatable, and multi-component
      inflatable penile prostheses over a five-year period. No intraoperative
      complications were encountered in our series. Major complications following
      discharge from the hospital were encountered in 6 patients (23.1%). After
      revision surgery, 4 patients (15.4%) eventually required removal of their penile
      implants. Good sexual satisfaction was noted in 18 patients (69.2%), while
      another 2 patients (7.7%) reported fair sexual satisfaction. Six patients (23.1%)
      expressed dissatisfaction with the procedure.

PMID- 8579317
TI  - Venous ligation for cavernous leak impotence--a report on 30 cases.
AB  - We report our experience with the surgical treatment of 30 patients with venous
      leak impotence seen at the Division of Urology, Toa Payoh Hospital, over a period
      from April 1991 to August 1993. The patients were assessed by history, clinical
      examination, hormonal evaluation and intracavernosal injection of papaverine.
      Confirmation of venous leak impotence was obtained by pharmaco-cavernosography in
      all patients; dynamic cavernosometry was performed in the later part of the
      series. Surgical treatment consisted of ligation and stripping of the deep dorsal
      vein, ligation of all its emissary and circumflex tributaries for all patients,
      with crural plication and suspensory ligament re-approximation in selected
      patients. Peroperative intracavernosal injection of papaverine was used to
      identify veins and to assess the adequacy of the extent of venous ligation. The
      mean age of the patients was 40 years. The average operative time was 2 hours.
      The usual period of hospitalisation was 3 days. Patients were followed up for an
      average period of 15.6 months. Success was defined as having adequate erections
      for normal coitus; the success rates at 1, 3, 6, 9 and 12 months were 76.2%,
      61.9%, 52.4%, 42.9% and 38.1%, respectively.

PMID- 8579318
TI  - An overview of acute scrotal pain.
AB  - Acute scrotal pain requires immediate medical attention to determine the
      underlying cause and to treat accordingly. The diagnosis may not be
      straightforward and in some patients, immediate surgery may be necessary in order
      to treat torsion of the testes early to achieve good results. The aim of this
      retrospective study is to evaluate the underlying causes and the outcome of acute
      scrotal pain. It includes a total of 116 patients over a period of 18 months who
      were admitted to the general urology ward. Seventy-six percent of the patients
      complained of pain only, 13% complained of pain with fever, 7% complained of
      urinary symptoms and 4% a combination of the three. After evaluation, 44 patients
      were diagnosed to have torsion of the testes and all of these patients were below
      20 years old. Thirty-eight of the patients complained of pain only and 2 had pain
      with fever. Two patients were thought to have torsion and exploration was
      performed. They were found to have infection. The rest had orchidopexy done and
      only 2 had orchidectomy due to infarction. Fifty-two patients had acute epididymo
      orchitis, 50 of these were above 20 years old and half (n = 25) of this group of
      patients admitted to having had exposure to sexually transmitted diseases, 11
      patients had a history of instrumentation and 14 had no known causes. From this
      study, age appeared to be the main differentiating point between torsion and
      epididymo-orchitis. for equivocal cases, new technology such as the Doppler
      ultrasound and testicular scan may be useful in future to improve the diagnosis
      of this urogenital emergency.

PMID- 8579319
TI  - The neurophysiology of sexual desire, with particular reference to paedophilia.
AB  - Bancroft has proposed a central arousability system as an androgen-sensitive
      neurophysiological substrate of sexual desire. The present paper describes the
      author's explorations of a brain-wave measure, the contingent negative variation
      (CNV), as a putative index of sexual desire under conditions of sexually-relevant
      stimulation in paedophilic child sex offenders and in non-offender control men.
      As a group, the former showed undifferentiated CNV responses to adult and child
      stimuli, unlike non-paedophilic child sex offenders and controls, who showed
      larger CNVs to adult than to child stimuli. These results suggest that CNV may be
      usefully developed as an adjunct to penile plethysmographic (PPG) assessment of
      deviant sexual interests in offenders. Some possible directions for future
      research are indicated.

PMID- 8579320
TI  - Sexual dysfunction in China.
AB  - In recent years, many sexual dysfunction cases cropped up in various parts of
      China. The number of hospital with sexual dysfunction clinics has also increased.
      They are concentrated more in the big or coastal cities. In these clinics,
      compared with those of the west, there is a greater proportion of retarded
      ejaculation cases and a lower proportion of female patients. Deficient sexual
      knowledge is the commonest cause of sexual dysfunction especially with respect to
      the sexual problems of the aged. The treatment approaches used by these clinics
      combine psychotherapy, behavioural therapy, medication and the application of
      physical aids, and are in line with modern international trends. However, these
      clinics are only in their infancy and still face many obstacles. The government
      is still quite stringent on the control of drugs for treatment of sexual
      dysfunctions and also sees many sex aids as obscene. However, in view of the
      rapid development, the Chinese readiness to accept new ideas, the diligence of
      the Chinese medical professionals and the establishment of the Chinese Sexology
      Association in 1994, it is hoped that China will soon become one of the more
      advanced countries in Asia for the treatment of sexual dysfunctions.

PMID- 8579321
TI  - An overview of sexual counselling.
AB  - The outcome of sexual counselling in the treatment of sexual dysfunction is
      reviewed. The results of Masters and Johnson's sex therapy, behaviour therapy and
      psychodynamic psychotherapy are discussed. Most studies suggest that two-thirds
      of patients respond to sex therapy. Advances in sex therapy of the future will
      require the formation of integrated, multidisciplinary, sexual dysfunction
      clinics, including marital, psychiatric, medical, urological and gynaecologic
      evaluations. Sex therapy combined with pharmacological injections and vacuum
      devices may be necessary.

PMID- 8579322
TI  - Adolescent sexuality and its problems.
AB  - Adolescent sexual activity is increasing globally. Abstinence and a delay in the
      start of sexual intercourse may be the most effective methods in preventing the
      consequences of teenage sexual activity. However, these goals are seldom met.
      With the change in social norms, peer pressure and media influences; teenagers
      are engaging in premarital sex earlier. Family life education in countries like
      Sweden and Finland reduces teenage pregnancy and abortion. It is unrealistic to
      expect sexually active adolescents to stop their sexual activity. An effective
      contraceptive method will provide an alternative to prevent teenage pregnancy.
      Issues on compliance of contraceptive use, especially at the very outset of
      sexual activity should be addressed. Most of the problems associated with teenage
      pregnancy are now thought to be related to the social circumstances of the
      mother, the poor nutritional status before pregnancy and poor attendance at
      antenatal clinics. Risk-taking behaviour in this age group will also make them
      more prone to contracting sexually transmitted diseases. High risk groups should
      be screened and treated early. Contraceptive methods with protection against
      sexually transmitted diseases should be advised.

PMID- 8579323
TI  - Clinical evaluation of impotence.
AB  - With better understanding of the pathophysiology of erectile dysfunction, various
      causes of impotence can be identified accurately with the help of different
      investigation modalities. However, it is controversial as to what extent
      investigations are considered as adequate because most of the time they do not
      influence patient management. The clinical evaluation of erectile dysfunction
      should include a thorough sexual and medical history and physical examination.
      Further special investigations such as nocturnal penile tumescence studies,
      duplex ultrasonography, dynamic infusion cavernosometry and cavernosography, and
      arteriography should only be ordered logically after careful consideration of
      whether they will affect patient outcome. Therefore in this review, we aim to
      evaluate critically these different special investigations with regards to their
      indications and pitfalls so that a logical approach to the evaluation of
      impotence can be obtained.

PMID- 8579324
TI  - Penile implant.
AB  - This paper reviews the various types of penile prostheses currently available in
      clinical practice. The advantages and disadvantages of each type of prosthesis
      are discussed. Practical factors to be considered in choosing the type of
      prosthesis offered to a patient are emphasised. The paper provides an outline of
      the important steps in the implantation surgery and also emphasises the need for
      patient and partner to have realistic expectations of the surgical result. While
      recognising the multiple forms of management of erectile impotence now available,
      the paper emphasises the high level of patient satisfaction which can be achieved
      using a penile prosthesis as the form of management of erectile impotence.

PMID- 8579325
TI  - Penile revascularization: an overview.
AB  - Penile revascularization offers the possibility to restoring natural erections in
      selected cases of vasculogenic impotence. Men who have an isolated block in the
      internal pudendal artery may be cured by anastomosis of the inferior epigastric
      artery to the dorsal penile artery. In men with congenital arterial dysplasia or
      cavernosal arterial disease, the corpora can be revascularized by the
      arterialization of the deep dorsal vein. In the Virag-type procedures, the
      epigastric artery is anastomosed to the deep dorsal vein at the base of the
      penis; blood flows retrograde through the veins and enters the corpora through
      the connecting posterior emissary veins. A new procedure that permits antegrade
      arterialization of the dorsal vein has been developed (Parulkar-Shah ADVA
      procedure). In this, the distal (glanular) half of the dorsal vein is completely
      mobilised, divided near the glans and then flipped back to lie upon the symphysis
      pubis where it is anastomosed end-to-end to the inferior epigastric artery. This
      procedure works on the same principle as the Virag procedure but has the
      advantage that the flow of blood is in the direction of the venous valves; hence
      the valves do not have to be ruptured. Venogenic impotence can be treated by
      dorsal vein arterialization in combination with venous ligation.

PMID- 8579326
TI  - Vaginismus and outcome of treatment.
AB  - Vaginismus is a condition of involuntary spasm of the muscles surrounding the
      outer third of the vagina that is brought about by real, imagined or anticipated
      attempts at vaginal penetration and often leads to non-consummation of marriage.
      It is a classic psychosomatic disorder where phobia of vaginal penetration often
      stems from sexual ignorance, previous traumatic experiences or religious
      orthodoxy. Management of vaginismus aims at helping the woman to regain voluntary
      control of her pelvic floor muscles. The treatment utilises a behavioural method
      aimed at teaching relaxation of pelvic floor muscles together with a systematic
      desensitization of the fear of vaginal penetration. There are two approaches to
      vaginal desensitization. The first is gradual desensitization using vaginal self
      dilatation, and the second method utilises rapid desensitization brought about by
      vaginal mould insertion. Of these, the rapid method is preferred at our
      institution. Surgical correction is almost never required and may be detrimental
      to achieving success. Management of these conditions requires a warm, empathetic
      attitude and demands great patience and understanding on the part of the
      physician. Between 1985 and 1991, 19 patients with vaginismus were treated at the
      National University Hospital, with a rapid desensitization programme using
      vaginal moulds. All 19 women could achieve satisfactory vaginal intercourse
      within 2 to 6 weeks of commencement of therapy.

PMID- 8579327
TI  - Present controversies in the genetics of male homosexuality.
AB  - Homosexuality refers to exclusive or predominant sexual attractions for persons
      of the same sex with or without physical relationship. In 1993, researchers in
      America identified the region of the X chromosome related to sexual orientation
      in homosexual men. However, molecular research of homosexuality does present
      particular problems because of the intense stigmatization some societies accord
      to these individuals. This paper presents the evidence of a genetic contribution,
      evaluates the complexity of sexual behaviour, and discusses the implications and
      challenges ahead if indeed a "gay gene" exists. It is apparent that scientific
      discoveries do not resolve moral dilemmas. The author believes that it is through
      debates and discussions that some ethical code can be, and should be formulated
      to prevent possible abuses.

PMID- 8579328
TI  - Overview of current operations for impotence.
AB  - Surgery is capable of correcting many causes of impotence but it is important for
      the surgeon to have a thorough understanding of the mechanisms of erection, to
      understand the limitations of current diagnostic techniques and be aware of the
      psychological needs of his patients. It is then possible to make the correct
      choice of operation to enable a man to have intercourse by correcting anatomical
      abnormalities, by restoring defective blood supply or by overcoming defects in
      the veno-occlusive mechanism. When these techniques are inappropriate, or fail,
      then the ability to have intercourse may be restored by the implantation of a
      penile prosthesis.

PMID- 8579329
TI  - Papaverine and prostaglandin E1 gel applications for impotence.
AB  - The transdermal permeability of papaverine and prostaglandin E1 (PGE1) could be
      determined in vitro. A chemical scheme of passive delivery or with enhancer, as
      well as a physical iontophoretic transdermal delivery system were designed in the
      laboratory. Clinically, up to 20% papaverine base gel and 500 micrograms PGE1
      were applied onto the genital area without any side effect. Only vascular
      response could be detected by ultrasound. However, immediate erection could not
      be obtained at the present dosage. Further research on the combination of skin
      absorption enhancers, the different chemical derivatives of PGE1 or a different
      administration route is warranted.

PMID- 8579330
TI  - A personal approach to the management of the complications of penile implant
      surgery.
AB  - Over the last 16 years more than 3000 procedures involving multi-component
      inflatable penile prostheses have been performed. A variety of types of
      complications have been encountered, including mechanical problems with the
      prostheses, intraoperative complications, postoperative complications, problems
      with infection and patient dissatisfaction. During the course of this experience
      we have made some observations and developed techniques to minimize and treat the
      complications seen with both routine and difficult inflatable penile prosthesis
      implantation surgery.

PMID- 8579331
TI  - Report and abstracts of the 4th International Workshop on Chromosome 9.
      Williamsburg, Virginia, USA, April 23-25, 1995.
AB  - The Fourth International Workshop on Chromosome 9 was a highly successful
      endeavor in terms of the growth of the map, both genetic and physical, the amount
      of data entered into GDB, and the continued comradeship in the sharing of data
      and resources that was exemplified. SIGMA remained a stable and valuable part of
      the chromosome 9 mapping effort. A new subsection outlining the morbid anatomy of
      chromosome 9 was included. Finally, specific goals were set for the community to
      aim for over the upcoming months. These included extending the information about
      the ease of use of genetic markers, and coordinating across numerous groups the
      meiotic breakpoint mapping of many microsatellite markers. Workshop files are
      available by anonymous ftp from ftp.gene.ucl.ac.uk (128.40.82.1) in the
      subdirectory/pub/c9workshop/1995, or by using a World Wide Web browser (such as
      Mosaic or Netscape) via the Chromosome 9 Home Page (at the URL
      http:@www.gene.ucl.ac.uk/chr9home.html).

PMID- 8579332
TI  - An integrated map of chromosome 9.
AB  - An integrated map of 211 loci on chromosome 9 is presented for which 198 loci
      have genetic locations. The results of the analysis indicate very strong
      interference for the chromosome and positional variations in recombination rates,
      most extreme in the male map where there is an excess of recombination near the p
      telomere and a marked suppression of recombination in a large region that
      includes the centromere.

PMID- 8579333
TI  - Exclusion from proximal 11q of a common gene with megaphenic effect on atopy.
AB  - We have typed three markers on proximal 11q in 131 random families with three or
      more children studied for atopy. A summary map that includes the FCER1B candidate
      was constructed. Using a 2-locus disease model, we performed combined segregation
      and linkage analysis of three models, none of which suggested linkage. Nine
      marker loci on other chromosomes were also negative. In the regions swept by
      these 12 markers we cannot rule out a rare gene, perhaps of large effect, nor a
      common gene of small effect. However, a common gene of large effect is excluded.
      These results and alternative strategies are discussed in the perspective of
      inconsistent evidence for a major atopy gene.

PMID- 8579334
TI  - Integrated genetic map of human chromosome 2.
AB  - A framework genetic map of human chromosome 2 is described, integrating data from
      the Centre d'Etude du Polymorphisme Humain (CEPH) version 6 database, the CEPH
      chromosome 2 consortium database, the National Institute of Health (NIH)/CEPH
      Collaborative Mapping group and other laboratories. A comprehensive map is also
      presented, showing regional locations of a large number of additional loci. The
      framework map is used to identify an informative set of meiotic breakpoints
      within the CEPH families, and the utility of this information for mapping new
      markers is discussed. The degree of typing error within the data set is
      estimated, as are the sex-specific interference parameters. A location database
      for these genetic and additional cytogenetic data is constructed using algorithms
      which map genetic distances on to a physical scale, and the potential for this
      approach to aid the integration of genetic and physical data is examined.

PMID- 8579335
TI  - An extension of the Maximum Lod Score method to X-linked loci.
AB  - The Maximum Lod Score method for affected relative-pair analysis, introduced by
      Risch, is a powerful method for detecting linkage between an autosomal marker
      locus and disease. In order to use the method to detect linkage to markers on the
      X-chromosome, some modification is necessary. Here we extend the method to be
      applicable to X-chromosomal data, and derive genetic restrictions on the
      haplotype-sharing probabilities analogous to the 'possible triangle' restrictions
      described by Holmans for the autosomal case. Size criteria are derived using
      asymptotic theory and simulation, and the power is calculated for a number of
      possible underlying models. The method is applied to data from 284 type 1
      diabetic families and evidence is found for the presence of one or more
      diabetogenic loci on the X-chromosome.

PMID- 8579336
TI  - Review of studies of polymorphic blood systems in the Aymara indigenous
      population from Bolivia, Peru, and Chile.
AB  - A review was made of all studies available from the literature referring to
      polymorphic blood systems of South American Aymara Indians. 33 original papers
      published up to 1990 covering a period of 45 years were summarized. Aymara
      samples were considered from a total of 55 localities in Bolivia, Peru, and
      Chile. Gene frequencies were tabulated for 21 polymorphic genetic systems
      comprising blood groups (AB0, MNSs, P, Rh, Lu, K, Le, Fy, Jk, Di), erythrocyte
      enzyme groups (AcP, 6PGD, PGM1, AK, ADA, EsD), and plasma protein groups (Hp, Tf,
      Gc, Gm, Km). Weighted average and range over all Aymara samples were computed for
      each blood system and compared with corresponding mean value and range in South
      Amerindians in general. Gene frequency distribution in the Aymara population
      shows ranges of different orders of magnitude in the 21 blood systems, some of
      them varying widely. Nevertheless the average gene frequencies for the Aymara are
      well within the range of values reported for South American Indian populations.
      The assessment of blood systems in the Aymara revealed that information
      concerning the Lutheran and HLA systems is scarce or nil up to now. Further
      studies are needed, especially from Peru on erythrocyte enzyme systems, in order
      to obtain a more complete picture on the variation of blood system polymorphisms
      in the Aymara population.

PMID- 8579337
TI  - Plasma protein polymorphisms (HP; TF and GC subtypes) in Friuli Venezia Giulia
      (northeast Italy).
AB  - Plasma protein genetic polymorphisms (HP; TF and GC subtypes) were studied in two
      different areas (Friuli Venezia Giulia and Istria). The results are discussed and
      compared with those reported by literature on other Italian and ex-Yugoslav
      population samples.

PMID- 8579338
TI  - Red cell 6-phosphogluconate dehydrogenase polymorphism in the Gadaba of Andhra
      Pradesh (India). Report of new variant phenotypes.
AB  - Blood samples from 1000 unrelated, adult individuals of the Gadaba tribal
      population were screened for 6-phosphogluconate dehydrogenase. We report the
      occurrence of a new fast moving variant, which is caused by the allele PGD*
      Gadaba. This allele is reported for the first time among the tribal populations
      of Andhra Pradesh. Its frequency comes to 0.0115, and it was observed in
      heterozygous (2.10%) and homozygous (0.10%) conditions.

PMID- 8579339
TI  - Red cell enzyme deficiencies in the tribal population groups of the Bastar
      District, Madhya Pradesh, India.
AB  - A total of 958 blood samples from Muria, Maria, Bhattra and Halba from the Bastar
      District in Madhya Pradesh (India) was collected and analyzed for glucose-6
      phosphate dehydrogenase deficiency, pyruvate kinase, hexokinase, and adenylate
      kinase red cell enzyme deficiency using flourescent technique. The implications
      of findings of the presence of rare enzyme deficiencies are discussed.

PMID- 8579340
TI  - Electrophoretic analysis of human hair keratins.
AB  - Non S-carboxymethylated human keratins, extracted from the hair of individuals
      from 3 Italian families, were characterized by one-dimensional sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing
      (IEF), after the separation of hair fibrous proteins (HFP) and hair matrix
      proteins (HMP) by gel filtration chromatography. By SDS-PAGE, HFP were separated
      into 3 polypeptide bands with apparent molecular weight (MW) 52 KDa, 44KDa and 40
      KDa; by IEF they were separated into several polypeptide bands with apparent
      isoelectric point (pI) in the pH range 7.4-4.0. By IEF, HMP were separated into
      several polypeptide bands with apparent pI in the pH range 7.4-5.4. It was not
      possible to characterize HMP by SDS-PAGE since their concentration, obtained
      after gel filtration chromatography, was very low. However, total extracted hair
      keratins were separated by SDS-PAGE into the polypeptides of HFP and into two
      bands with apparent MW 16 KDa, and 12 KDa. It was not possible to point out any
      interindividual variability in the electrophoretic patterns, except for one
      woman, for whom cosmetic treatment of hair could not be excluded. Finally,
      electrophoretic patterns for subjects of the same family are more similar than
      for unrelated subjects. Electrophoretic analysis of fractionated hair keratins
      could be useful for a better characterization of these polypeptides in genetic
      studies.

PMID- 8579341
TI  - [Dynamics of the growth intensity of Jena school children since 1880].
AB  - The intensity of growth of Jena school children at the age of 7 to 14 years has
      been investigated between 1880 and 1985. In the regarded 105 years the intensity
      of growth showed little changes with the tendency of a gradual increase. The
      analysis differentiated for age reveals partially different results compared for
      the whole interval between 7 and 14 years. These differences result from a
      shifting of phases of intensified growth into ontogenetically earlier age stages,
      which can be traced back to the secular trend. The increase of the growth
      intensity caused by the secular trend is significantly smaller in the school age
      than in the preschool age.

PMID- 8579342
TI  - Five anthroposcopic traits of the ear in a Malaysian population.
AB  - Five anthroposcopic traits concerning the ear, namely ear lobe attachment,
      position of ears, shape of the helix, presence of Darwin's tubercle and hairy
      ears have been studied in a Malay population from Malaysia. The results of the
      present study are compared with similar reports in other ethnic groups.

PMID- 8579343
TI  - Preparation of Tyr-C-peptide from genetically altered human insulin precursor.
AB  - C-peptide radioimmunoassay (C-peptide RIA) is widely used in determination of
      pancreatic B-cell secretion activity. 125I labeled Tyr-C-peptide is indispensable
      in C-peptide RIA kit. Herein we discuss a way of obtaining recombinant Tyr-C
      peptide. Arg32Tyr human pro-insulin mutant (R32Y-proinsulin) gene was constructed
      by site-directed mutagenesis and overexpressed in Escherichia coli. Purified R32Y
      proinsulin was converted to insulin and Tyr-C-peptide by trypsin and
      carboxypeptidase B codigestion. Tyr-C-peptide was isolated through reverse-phase
      HPLC (RP-HPLC) and identified by C-peptide RIA and amino acid analysis.

PMID- 8579344
TI  - Superactivity of peroxidase solubilized in reversed micellar systems.
AB  - Vaccinium mirtyllus peroxidase solubilized in reversed micelles was used for the
      oxidation of guaiacol. Some relevant parameters for the enzymatic activity, such
      as pH, w(o) (molar ratio water/surfactant), surfactant type and concentration,
      and cosurfactant concentration, were investigated. The peroxidase showed higher
      activities in reversed micelles than in aqueous solution. The stability of the
      peroxidase in reversed micelles was also studied, namely, the effect of w(o) and
      temperature on enzyme deactivation. The peroxidase displayed higher stabilities
      in CTAB/hexanol in isooctane reversed micelles, with half-life times higher than
      500 h.

PMID- 8579345
TI  - Purification of a glucose/mannose specific lectin, isoform 1, from seeds of
      Cratylia mollis Mart. (Camaratu bean).
AB  - A quantitatively main molecular form of Cratylia mollis lectin, isoform 1 (iso 1)
      was purified by affinity chromatography on Sephadex G-75, followed by ion
      exchange chromatography on CM-cellulose. Another lectin form was identified in
      the latter step. Iso 1 is specific for glucose/mannose, with a main subunit of 31
      kDa mol wt; the native protein is basic (pI 8.5-8.6) and the constituent
      polypeptides had a pI range of 5.15-7.75. An antibody to the protein was raised
      in a rabbit, and the conjugate was active in an immunosorbent assay.

PMID- 8579346
TI  - Where has all the caring gone?

PMID- 8579347
TI  - Perspectives of participative management in nursing.
AB  - Nursing administration takes on a bureaucratic orientation in Brazil. In this
      article, the authors report a strategy of participative management as a useful
      resource for transforming bureaucratic organizations. Principles of participative
      management, in the context of a social model of management, are presented and
      applied to nursing.

PMID- 8579348
TI  - Psychophysiological responses after sudden cardiac arrest during hospitalization.
AB  - A sample of 21 sudden cardiac arrest (SCA) survivors were interviewed every 48
      hours during hospitalization to determine emotional, cognitive, and physiological
      parameters of recovery. On the average, SCA survivors were not excessively
      anxious, depressed, angry, or confused during hospitalization, but they did
      report high levels of denial and uncertainty. The two most predominant cognitive
      impairments at the time of hospital discharge were loss of short-term memory and
      construction ability. Both the number of cardiac arrhythmias and the types of
      interventions used to manage them decreased as hospital discharge approached.

PMID- 8579349
TI  - Effects of intraoperative progress reports on anxiety levels of surgical
      patients' family members.
AB  - A three-group quasi-experimental posttest-only design was used to examine the
      effectiveness of intraoperative progress reports by comparing family members'
      state-anxiety score, mean arterial pressure level (MAP), and heart rate during
      elective surgical procedures. Control-group family members (n = 50) received
      usual care. Family members in the experimental group (n = 50) received a 5- to 10
      minute progress report protocol about halfway through a surgical procedure. An
      additional group of family members (n = 50) received an attention protocol.
      Family members in the experimental group reported lower state-anxiety scores (p <
      .001) and had significantly lower MAP levels (p < .001) and heart rates (p < .01)
      compared with the control and attention groups. Progress reports appear to be a
      beneficial independent nursing intervention for reducing anxiety in family
      members during the intraoperative waiting period.

PMID- 8579350
TI  - Nurses' acceptance of behavioral treatments and pharmacotherapy for behavioral
      disturbances in older adults.
AB  - Behavioral disturbances are common in elderly individuals, particularly in those
      suffering from dementia. Nurses are called on to manage these problem behaviors
      both in the nursing home and through home health care. There has been growing
      interest in nonpharmacological interventions for these problems, most notably
      behavioral therapies. However, until recently, no information was available
      regarding the acceptance by health care professionals on the use of these
      treatments with elderly individuals. The purpose of this study was to assess
      geriatric nurses' acceptance of two behavioral treatments (differential
      reinforcement of incompatible behavior and time-out from positive reinforcement)
      and the most commonly used treatment at this time, pharmacotherapy. Nurses were
      asked to read a clinical case vignette and three treatment descriptions, rating
      the treatments with Kazdin's Treatment Evaluation Inventory. Results show that
      both behavioral treatments, including a mildly aversive treatment (time-out) were
      rated more positively than pharmacotherapy. Nurses modified their ratings in
      response to described differences in the patient's cognitive functioning and
      place of residence. Most interesting, acceptability ratings were influenced by
      characteristics of nurse raters, including the nurses' educational background and
      the amount of contact with geriatric patients.

PMID- 8579351
TI  - The response of women to gender stereotyping during a health interview.
AB  - Gender-stereotypical responses and critical health information were examined in
      this posttest-only experiment. Thirty-eight university women students and staff
      were randomly assigned to a gender-stereotyped or a nonstereotyped health
      interview. Gender-biased cues were embedded in three of the five questions in the
      gender-stereotyped interview. Women in the gender-stereotyped interview responded
      with significantly more gender-stereotypical responses. However, no subjects felt
      affected by the gender-biased cues. Findings suggest that women affirm gender
      biased questions asked in health interviews.

PMID- 8579352
TI  - Health concerns and prevalence of abuse and sexual activity in adolescents at a
      runaway shelter.

PMID- 8579353
TI  - Screening for child abuse: problems and possibilities.

PMID- 8579354
TI  - Is it research?
AB  - Although the two important processes have many shared methods, they also have
      distinct features that need to be made explicit, especially when sharing findings
      in a public arena. Let nurses take the lead in forthright reporting of findings,
      by clearly identifying their origins and making recommendations for future
      investigations--both in research and organizational improvement projects.

PMID- 8579355
TI  - Cloning and characterization of cDNA encoding the rabbit tRNA-guanine
      transglycosylase 60-kilodalton subunit.
AB  - Eukaryotes synthesize queuosine (nucleoside Q) by the irreversible base-for-base
      exchange of queuine (Q base) for guanine at tRNA position 34, a reaction
      catalyzed by tRNA-guanine transglycosylase (TGT). The physiological role of Q
      remains unknown but the tRNA of tumor cells often is undermodified with respect
      to Q. Toward an understanding of the function of Q in normal and neoplastic cells
      we have isolated and characterized the cDNA for rabbit TGT. Rabbit erythrocyte
      TGT was reported previously to be a dimer of 60- and 43-kDa subunits (N. K. Howes
      and W. R. Farkas, 1978, J. Biol. Chem. 253, 9082-9078). Here we present the cDNA
      sequence for the apparent 60-kDa subunit; it contains an open reading frame
      encoding a 493-residue protein. The rabbit TGT 60-kDa subunit shares significant
      sequence similarity with the deubiquitinating enzyme family (F. R. Papa and M.
      Hochstrasser, 1993, nature 366, 313-319), especially with sequence elements that
      include conserved Cys and His residues.

PMID- 8579356
TI  - Differential effects of N- and C-terminal deletions on the two activities of
      rubisco activase.
AB  - Spinach (Spinacea oleracea) leaf ribulose-1,5-bisphosphate carboxylase/oxygenase
      (rubisco) activase was subjected to limited proteolysis with trypsin and directed
      deletions were made by modifying the spinach rubisco activase cDNA and expressing
      the 41-kDa isoform in Escherichia coli. Protein exposed to trypsin displayed a
      more rapid loss of the ability to promote the activation of decarbamylated
      rubisco than ATP hydrolysis (e.g., 10 and 50% activity remaining, respectively,
      after 1 h). A series of N-terminal deletions exhibited near abolition of rubisco
      activation after the 12th residue, a conserved tryptophan, was deleted.
      Conversely, a deletion of 19 residues at the C-terminus increased rubisco
      activation with little effect on ATP hydrolysis, resulting in an increased
      efficiency of activation. The C-terminal deletion mutant was further modified by
      a site-directed mutation in the ATP binding region (Q109E) which was previously
      observed to increase the efficiency of activation (J. B. Shen and W. L. Ogren,
      1991, Plant Physiol. 99, 1201-1207). The efficiency of activation with this
      double mutant was greater than that for either of the original mutants. The
      results indicate that a conserved tryptophan in the N-terminal portion of rubisco
      activase is critical for promotion of the activation of rubisco, consistent with
      a possible role in interaction with rubisco. The C-terminus appears to have a
      regulatory effect on both rubisco activation and ATP hydrolysis.

PMID- 8579357
TI  - Long-chain acyl-CoA hydrolase from rat brain cytosol: purification,
      characterization, and immunohistochemical localization.
AB  - Long-chain acyl-CoA hydrolase (EC 3.1.2.2), which is found primarily in the brain
      in rats, catalyzes the hydrolysis of fatty acyl-CoA thioesters. We purified this
      enzyme, referred to as ACH, from the rat brain cytosol. The molecular masses of
      the native enzyme and the subunit were estimated to be 104 and 36 kDa,
      respectively. The enzyme showed high activity with long-chain acyl-CoAs, e.g.,
      with maximal velocity of 262 mumol/min/mg and Km of 5.7 microM for palmitoyl-CoA,
      but acyl-CoAs with carbon chain lengths of C8-18 were also good substrates. The
      enzyme was refractory to the inhibitory effect of diisopropyl fluorophosphate and
      phenylmethylsulfonyl fluoride, but sensitive to p-chloromercuribenzoate. In the
      rat brain cytosol, about 90% of palmitoyl-CoA hydrolase activity was titrated by
      anti-ACH antibody, which accounted for over 70% of the enzyme activity found in
      the brain tissue. Immunoblots of the cytosol prepared from rat brain regional
      blocks indicated the broad distribution of ACH over the brain, with a relatively
      high level in the pons and medulla. Immunohistochemically, ACH was localized to
      neurons. In addition to various nuclei, some neuronal cells, such as mitral cells
      in the olfactory bulb, pyramidal cells in the cerebral cortex, and Purkinje cells
      in the cerebellum, were also immunostained with anti-ACH antibody. Brain cytosols
      prepared from ten mammalian species including human contained a single
      polypeptide reactive to anti-ACH antibody with molecular masses of 34-36 kDa,
      together with high activities of palmitoyl-CoA hydrolase. These findings suggest
      the physiological significance of ACH in the brain, although its precise role
      remains to be determined.

PMID- 8579358
TI  - A detergent-sensitive 113-kDa conformer/complex of CD36 exists on the platelet
      surface.
AB  - The membrane protein CD36 has been implicated in platelet and monocyte signal
      transduction events and is known to be tightly associated with cytosolic protein
      tyrosine kinases. CD36 contains an extremely small cytoplasmic domain(s) and the
      mechanism by which CD36 interacts with cytosolic kinases is unknown. In the
      present study, CD36 (M(r) 88,000) has been detected on the surface of platelets
      as a conformational isoform or complex of apparent M(r) 113,000. In intact
      platelets crosslinked with bis(sulfosuccinimidyl)suberate, approximately 50% of
      cell surface CD36 existed as the 113-kDa form. When detergent extracts of
      platelets were crosslinked, the amount of CD36 in the 113-kDa form was found to
      be dependent on the detergent used. The 113-kDa form of CD36 was 10-fold more
      prevalent in Triton X-100 extracts than in extracts made with the zwitterionic
      detergent 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate (CHAPS).
      Addition of Triton X-100 to CHAPS platelet extracts resulted in recovery of the
      113-kDa form of CD36. These studies suggest that CD36 exists on the surface of
      platelets as a heterodimeric complex of CD36 and another protein(s) or exists in
      two different conformational states which, when covalently crosslinked, exhibit
      an apparent M(r) of 113,000. Further characterization of the 113-kDa form of CD36
      may help define CD36-kinase interactions.

PMID- 8579359
TI  - Stabilization of the tetrameric structure of human and bovine hemoglobins by
      pseudocrosslinking with muconic acid.
AB  - In previous studies mono-3,5-dibromosalicyl-fumarate was used to introduce an
      intramolecular crosslink (pseudo-crosslink) in the beta cleft between hemoglobin
      beta subunits. Sedimentation velocity analysis indicated that the product had a
      mean molecular weight indicating a tetramer with low dissociability. The product
      had a P50 higher than that of native hemoglobin and a plasma retention time in
      the rat of about 3 h, i.e., four times longer than untreated hemoglobin. However,
      the product contained a fraction which was rapidly eliminated in the urine and
      which had a short plasma half-time of about 20 min, indicating the presence of a
      dissociable fraction. We have attempted to further enhance the tetrameric
      stability of hemoglobin and prevent urine elimination by positioning a longer
      chain carboxylic acid than fumaric acid into the beta cleft. We reason that a
      longer molecule would allow for greater stabilizing interactions across the beta
      cleft. In the present study human and bovine hemoglobins were reacted with mono-3
      5-dibromosalicyl muconate. Muconic acid is two carbons longer than fumaric acid.
      The products were acylated at the beta 82 (human) and beta 81 (bovine) lysines of
      the beta-cleft and had a low degree of dissociability. For reasons not presently
      understood, urine excretion was high and plasma half-time was not increased above
      that of untreated hemoglobin. In conclusion, it appears that only covalently
      crosslinked hemoglobins which are completely nondissociable tetramers escape
      filtration; tetramers with any degree of dissociability into dimers are
      filterable.

PMID- 8579360
TI  - Mutations at histidine 211 of the yeast F1-ATPase beta-subunit affect the
      stability and assembly of the ATPase and the structure of the active site.
AB  - The role of H211 of the yeast F1-ATPase beta-subunit was investigated by site
      specific mutagenesis and characterization of the resulting enzymes. Five amino
      acids (N, D, I, K, and A) were substituted for H211 of the ATP2 gene. The mutated
      genes were expressed in an atp2::LEU2 host, and only yeast expressing H211N
      respired aerobically. The respiratory phenotypes of the other four mutants were
      suppressed by a second site mutation (L203F). The ATPases from the single mutant
      strains were unstable when removed from the mitochondrial inner membrane,
      preventing purification. Submitochondrial particles were prepared from each
      strain and the activities were stable under a variety of conditions, allowing
      determination of Vmax and Km for ATP hydrolysis. Mutations of H211 caused
      increases in Km of 3.7- to 7.4-fold, while L203F had little effect. The
      suppressive effect of the L203F mutation was also expressed in the Km values of
      the double mutant strains. The ATPases from the H211 mutants had diminished
      sensitivity to oligomycin, and their pH optima were 1.5-2.0 units less than the
      wild-type optimum. Values of pKa for the groups involved in catalysis were
      estimated for the wild-type enzyme and three H211 mutants (N, D, and K). Each
      mutant enzyme showed a substantial decrease in the pKa of the group(s) which
      serves as a base in acid-base catalysis. The results of this study demonstrate
      that H211 is important in maintaining the structure of the wild-type enzyme
      complex and also contributes to the structure of the active site. L203 is also
      required for the stability of the enzyme complex and may have a structural or
      functional interaction with H211. Neither H211 nor L203 is required for catalysis
      by F1.

PMID- 8579361
TI  - Transcriptional inhibition of cytochrome P4502E1 by a synthetic compound, YH439.
AB  - The molecular mechanism of cytochrome P4502E1 (CYP2E1) inhibition by a synthetic
      compound, YH439, was studied. In rats treated with YH439, N-nitrosodimethylamine
      demethylase activity and the amount of immunoreactive CYP2E1 were rapidly
      decreased in time- and dose-dependent manners. Within 2 h after a single dose of
      YH439 (150 mg/kg), the CYP2E1-catalyzed activity in uninduced rats was decreased
      by about 30% and by 43% at 24 h after YH439 injection. YH439 treatment also
      reduced the elevation of CYP2E1 enzyme activity in starved (induced) animals by
      34%. More profound inhibition of CYP2E1 protein levels was observed by immunoblot
      analysis. The level of CYP2E1 catalytic activity and immunoreactive protein
      remained suppressed for at least 48 h and returned to normal level at 72 h after
      YH439 treatment. The levels of immunoreactive CYP2B1/2 protein and catalytic
      activity were moderately increased while little change was observed in the levels
      of NADPH-dependent P450 oxidoreductase activity and its protein after treatment
      with YH439. Unlike competitive inhibitors of CYP2E1, YH439 rapidly (within 2 h)
      decreased the level of CYP2E1 mRNA, while malotilate, a structural analog of
      YH439, slightly suppressed its level. Nuclear run-on transcription analyses at 2,
      4, and 8 h post-YH439 administration revealed that the inhibition of CYP2E1 by
      YH439 is at the level of transcription, indicating that YH439 is a new class of
      CYP2E1 inhibitor. Our data demonstrate that YH439 is a powerful inhibitor of
      CYP2E1 expression and is thus potentially useful as a pharmacological tool to
      study CYP2E1 function as well as a potential therapeutic agent.

PMID- 8579362
TI  - Identification of an arginine residue in the dual coenzyme-specific glucose-6
      phosphate dehydrogenase from Leuconostoc mesenteroides that plays a key role in
      binding NADP+ but not NAD+.
AB  - Glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides can utilize
      either NADP or NAD as coenzyme. The enzyme's three-dimensional structure has been
      solved (Rowland et al., 1994, Structure 2, 1073-1087) and shown to contain a
      conventional nucleotide binding domain. NADP+ was modeled into the structure by
      superimposing the beta alpha beta domain and that of coenzyme-bound 6
      phosphogluconate dehydrogenase (Adams et al., 1994, Structure 2, 651-658),
      enabling us to identify Arg-46 as a potentially important residue for NADP+
      binding. Using site-directed mutagenesis, we constructed mutant enzymes in which
      Arg-46 was replaced by glutamine (R46Q) and alanine (R46A) and examined their
      kinetic properties. The principal effects in these mutant enzymes were that the
      Km and Ki values for NADP+ increased by 2 to 3 orders of magnitude over those of
      the wild-type enzyme. No other kinetic constant was altered more than 6.5-fold.
      Changing this single amino acid leads to mutant glucose-6-phosphate
      dehydrogenases with coenzyme specificities that favor NAD+, whereas the wild-type
      enzyme prefers NADP+ as coenzyme. These results confirm that Arg-46 plays a key
      role in NADP+ binding by contributing a positively charged planar residue that
      interacts primarily with the 2'-adenosine phosphate. The Arg residue
      corresponding to Arg-46 in L. mesenteroides glucose-6-phosphate dehydrogenase is
      conserved in all glucose-6-phosphate dehydrogenases and, presumably, plays the
      same role in all these enzymes.

PMID- 8579363
TI  - Pentamidine is an uncoupler of oxidative phosphorylation in rat liver
      mitochondria.
AB  - Pentamidine is a cationic drug that is used for the treatment of African
      trypanosomiasis, leishmaniasis, and Pneumocystis carinii pneumonia. When
      incubated with pharmacological concentrations of pentamidine, some of the
      etiologic agents of those diseases reach internal concentrations close to 1.0 mM.
      In this work pentamidine is shown to exhibit characteristics of a cationic
      uncoupler of oxidative phosphorylation in isolated rat liver mitochondria: it
      released respiratory control, enhanced the latent ATPase activity, and released
      the inhibition of State 3 respiration by oligomycin. Maximal stimulation of
      respiration and ATPase activity was observed at a concentration of pentamidine of
      200-300 microM. Higher concentrations had an inhibitory effect on mitochondrial
      respiration. As it happens with other cationic uncouplers, the uncoupling effect
      of pentamidine required inorganic phosphate. Pentamidine-induced uncoupling of
      oxidative phosphorylation was accompanied by an efflux of Ca2+ from the
      mitochondria and partial collapse of the mitochondrial membrane potential.

PMID- 8579364
TI  - Participation of nitric oxide and iron in the oxidation of DNA in asbestos
      treated human lung epithelial cells.
AB  - Treatment of human lung epithelial (A549) cells with crocidolite resulted in the
      formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the DNA, synthesis of mRNA
      for the inducible form of nitric oxide synthase (NOS), and increased
      intracellular nitrite (NO2-), a stable oxidation product of NO. Iron, associated
      with crocidolite, was involved in both NO2- and 8-OHdG formation. Addition of the
      NOS inhibitor, aminoguanidine (AG), reduced intracellular NO2- and prevented
      formation of 8-OHdG in crocidolite-treated cells, suggesting that NO was required
      in 8-OHdG formation. Addition of an NO-generating compound, diethyltriamine/NO,
      with AG and crocidolite resulted in recovery of 8-OHdG, further supporting a role
      for NO in oxidation of deoxyguanosine.

PMID- 8579365
TI  - 13C NMR analysis of the use of alternative donors to the tetrahydrofolate
      dependent one-carbon pools in Saccharomyces cerevisiae.
AB  - Serine is generally accepted as the major one-carbon donor in folate-mediated one
      carbon metabolism in most cells. Previous work from our laboratory with the yeast
      Saccharomyces cerevisiae has demonstrated that glycine and formate can also
      provide one-carbon units. Under normal growth conditions, it is likely that cells
      utilize serine, glycine, formate, and perhaps other one-carbon donors
      simultaneously, but to differing degrees. In the present work, we have used 13C
      NMR to monitor how yeast cells distribute alternative, competing one-carbon
      sources into various pools. Cells were grown with [2-13C]glycine and unlabeled
      formate or folinic acid (leucovorin, 5-formyl-tetrahydrofolate) as competing one
      carbon sources. The relative contribution of each one-carbon donor to the three
      oxidation states of the tetrahydrofolate-bound one-carbon pool [5-methyl
      tetrahydrofolate (CH3-THF), 5,10-methylene-THF (CH2-THF), and 10-formyl-THF (10
      CHO-THF)] was determined by analysis of two metabolic end products of one-carbon
      metabolism, choline and adenine. Glycine-derived 13C-labeled one-carbon units are
      incorporated into these two metabolites; dilution of the 13C indicates
      competition by the unlabeled one-carbon source. The results reveal that the
      contribution from formate, folinic acid, and glycine is different for each of the
      one-carbon pools. Formate competed most dramatically at the 10-CHO-THF pool, with
      decreasing competition into the CH2-THF and CH3-THF pools. In a mutant strain
      lacking cytosolic CH2-THF dehydrogenase activity, a distinct shift toward the use
      of glycine instead of formate as the source of one-carbon units for the more
      reduced pools (CH2-THF and CH3-THF) was observed, while 10-CHO-THF pools were not
      affected. In contrast, the formyl group of folinic acid competed almost
      exclusively at the 10-CHO-THF level, with barely detectable dilution of the CH2
      THF and CH3-THF pools in wild-type cells. The mutant strain exhibited essentially
      identical results, confirming that 5-formyl-THF enters the active one-carbon pool
      at the level of 10-CHO-THF, presumably via 5,10-methenyl-THF. Furthermore,
      donation of one-carbon units by folinic acid was observed only when cells were
      depleted of THF by treatment with the dihydrofolate reductase inhibitor
      methotrexate. These results reveal that the state of equilibrium between one
      carbon pools in a growing cell depends on the source of the one-carbon units.
      This work illustrates the power of 13C NMR for examining the in vivo utilization
      of alternative one-carbon donors under a variety of conditions.

PMID- 8579366
TI  - Modulation of the rat alveolar macrophage respiratory burst by hydroperoxides is
      calcium dependent.
AB  - Sublethal concentrations of hydroperoxides (H2O2 or tert-butylhydroperoxide)
      produce a dual effect upon the respiratory burst of rat alveolar macrophages in
      which low concentrations (< 50 microM) enhance and higher concentrations (> 50
      microM) produce inhibition (J. K. Murphy, et al., Free Radical. Biol. Med. 18, 37
      45, 1995). These effects correlate with transient versus sustained elevation of
      [Ca2+]i caused by exposure to hydroperoxides prior to stimulation of the
      respiratory burst. In the present study changes in [Ca2+]i caused by exposure to
      sublethal levels of hydroperoxide were buffered by incubating macrophages with
      the acetoxy-methyl ester of BAPTA, an intracellular Ca2+ chelator. The
      enhancement of the phorbol ester-stimulated respiratory burst by tBOOH was
      abolished by BAPTA, while the inhibition was attenuated. Thus, the modulation by
      tBOOH appears to be largely dependent upon the changes in [Ca2+]i. Receptor
      mediated stimulation of the respiratory burst (ADP stimulation) involves release
      of Ca2+ from the inositol-1,4,5-triphosphate (IP3)-sensitive pool in the
      endoplasmic reticulum. Comparisons were made of the effects of thapsigargin (TG),
      an endoplasmic reticulum Ca-ATPase inhibitor, with tBOOH on release of
      intracellular Ca2+ and the respiratory burst. Treatment with TG did not affect
      changes in [Ca2+]i caused by tBOOH or vice versa. Although TG decreased the ADP
      stimulated respiratory burst, it had no effect upon tBOOH modulation. Thus, the
      effect of tBOOH upon the respiratory burst is dependent upon the release of Ca2+
      and the release of Ca2+ occurs from a non-IP3-dependent pool. This aberrant
      mimicry of normal signal transduction underlies oxidative modulation of the
      respiratory burst.

PMID- 8579367
TI  - Possible relationship between conditions associated with chronic hypoxia and
      brain mitochondrial DNA deletions.
AB  - The brain relies heavily on aerobic metabolism which requires functional
      mitochondria. Mitochondria are subcellular organelles with their own genome which
      codes for 13 essential protein subunits. By employing PCR assays to examine brain
      tissue from 43 age-comparable individuals (between ages 34 and 73), we found a
      correlation between mitochondrial DNA deletion mutations, mtDNA4977 deletions,
      and conditions associated with chronic hypoxia. In prior studies, utilizing only
      6 to 12 clinical samples, mtDNA4977 deletions were reported to increase in
      specific regions of the brain with aging. However, we found 12-fold and 5-fold
      higher levels of mtDNA4977 deletions in the putamen and the superior frontal
      gyrus of the cortex, respectively, from individuals who had conditions associated
      with chronic hypoxia when compared with individuals without evidence of such
      conditions. These findings suggest that chronic hypoxia should be more closely
      examined in the pathophysiology of central nervous system diseases.

PMID- 8579368
TI  - cDNA cloning and sequence analysis of a lysine-49 phospholipase A2 myotoxin from
      Agkistrodon contortrix laticinctus snake venom.
AB  - A cDNA clone (ACLPREMT1) for a K49 phospholipase A2 (PLA2) myotoxin from
      Agkistrodon contortrix laticinctus snake venom was isolated from a venom gland
      library and sequenced. The ACLPREMT1 cDNA is 734 bp in length and has an open
      reading frame of 414 bp. It codes for a K49 phospholipase A2 with 121 amino acid
      residues. The sequence of the first 20 amino acid residues of the predicted
      mature protein matches exactly with the N-terminal sequence of the purified
      myotoxin. Comparison of the ACLPREMT1 cDNA sequence with PLA2 cDNAs from
      Viperidae snakes shows that it has a similar organization: highly conserved 5'
      and 3' untranslated regions, a sequence encoding a 16-amino acid signal peptide,
      and the mature protein coding region. Comparison of the predicted sequence of ACL
      myotoxin and other K49 and D49 PLA2 myotoxins shows that, despite the homology
      (85-97%) at the nucleotide level, K49 PLA2 myotoxins are distinct from the D49
      PLA2s and form a highly conserved protein family. In addition to the substitution
      of D49K, K49 myotoxins have several invariant residues not found in the D49
      group, including K7, K78, K80, K115, and K116. There are also some conserved
      residues (E12, T13, K16, and N17) in all myotoxic proteins, including some
      neurotoxic and myotoxic PLA2s. Molecular modeling of ACL myotoxin shows that
      these residues are close together on the surface of one side of the molecule
      which suggests a potential site for binding to membranes and/or induction of
      toxicity.

PMID- 8579369
TI  - Calcium waves in fluid flow stimulated osteoblasts are G protein mediated.
AB  - Calcium (Ca2+) entry upon cell perturbation has been examined in transformed
      human osteoblast cells (U-2/OS). The cells were deformed by fluid flow from a
      patch pipette held in proximity to the cell by applying a positive pressure (+50
      mm Hg) for the passage of saline over the membrane. Intracellular calcium [Ca2+]i
      was examined following loading with 5 microM Fura-2 AM. The changes in ratio were
      determined at 330-ms intervals. Waves of [Ca2+]i were seen spreading along the
      length of the individual cell following stimulation (n = 30). The initial change
      in Ca2+ at the site of stimulation occurred within 660 ms after applying the
      stimulus. Following 1.3 (+/- 0.33) s of raised [Ca2+]i, the values returned to
      those of predeformation. The Ca2+ response following fluid flow stimulation was
      blocked by 300 microM Cd2+, a specific blocker of Ca2+ channels, demonstrating an
      extracellular source of Ca2+. Preincubation with cholera toxin (250 ng/ml for 6
      h) prolonged the elevation of Ca2+ induced by fluid flow stimulation (n = 20). In
      contrast, pertussis toxin (250 ng/ml for 6 h) completely eliminated the Ca2+
      response to fluid flow stimulation (n = 20). Cells maintained in solutions free
      of Ca2+ demonstrated no change in [Ca2+]i. Tetraethylammonium (6 mM) had no
      effect on the response (n = 10). In addition pretreatment with ryanodine (2 and
      10 microM; each group n = 10) in media showed a reduced wave of Ca2+ in response
      to mechanical deformation. The response to a phospholipase C inhibitor also
      eliminated the response to the mechanical deformation (n = 10). In addition cells
      that demonstrated changes in Ca(2+)-containing media lost the ability to respond
      when EGTA was added to the media. Following this, 2 microM ryanodine was added to
      the cells, demonstrating a response too small to replicate the fluid flow
      stimulated wave, but supporting the view that the cells were vital following
      preincubation.

PMID- 8579370
TI  - Low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor
      on murine peritoneal macrophages mediates the binding and catabolism of low
      density lipoprotein.
AB  - Low-density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin
      receptor is a member of the low-density lipoprotein receptor family. It is known
      to bind a wide variety of unrelated ligands including alpha 2-macroglobulin
      proteinase complexes, tissue plasminogen activator, apolipoprotein E-enriched
      very low density lipoprotein, lipoprotein lipase, and Pseudomonas exotoxin A.
      Receptor-associated protein (RAP), a protein which copurifies with LRP, can
      inhibit the binding and internalization of all known ligands to LRP. Recent
      studies have shown that some ligands can bind to more than one receptor in this
      family. However, the ability of low-density lipoprotein (LDL) to bind to LRP in
      addition to the LDL receptor has not been demonstrated consistently. In this
      study we demonstrate that LDL binds with high affinity to macrophage cell surface
      receptors at 4 degrees C (Kd = 1.8 nM) and competes for the binding of a receptor
      recognized form of alpha 2-macroglobulin (alpha 2M*) (Ki = 3 nM). alpha 2M* and
      RAP can inhibit the binding of LDL to macrophages completely (96 and 100%
      inhibition, respectively), after cell surface heparin has been removed by
      treatment with heparinase. Using a solid-phase assay, we show that LDL binds
      specifically, saturably, and with high affinity to purified LRP (Kd = 5 nM). LDL
      can also completely inhibit the binding of alpha 2M* to purified LRP. These
      results indicate that LDL binds directly to LRP. The ability of LDL to cross
      compete with alpha 2M* for binding to LRP suggests that LDL binds to a similar or
      overlapping site as alpha 2M*. In addition, the ability of alpha 2M* to inhibit
      most of the receptor-mediated binding of LDL to macrophages suggests that LDL
      receptors on murine peritoneal macrophages are predominantly LRP.

PMID- 8579371
TI  - Escherichia coli biotin synthase: an investigation into the factors required for
      its activity and its sulfur donor.
AB  - Biotin synthase catalyzes the chemically difficult final step in the biotin
      biosynthetic pathway and is encoded by the bioB gene in Escherichia coli. In the
      present work, we extend our characterization of this enzymatic reaction and the
      extensive set of factors required by it. A defined mixture of components that
      supports the biotin synthase reaction has been found. The mixture contains biotin
      synthase, flavodoxin, flavodoxin reductase, NADPH, Ado-Met, Fe, fructose-1,6
      bisphosphate, cysteine, and dithiothreitol. Even though this defined mixture
      supports the biotin synthase reaction, and in that regard is an important step
      forward in the study of this enzyme, it is unlikely that it contains all the
      physiologically significant factors involved in the biotin synthase reaction
      since it supports as an upper limit the synthesis of only 2 mol of biotin per
      mole of biotin synthase monomer. Progress in our efforts to identify additional
      physiologically significant factors is also reported. First, we describe evidence
      that the fructose 1,6-bisphosphate in the defined reaction mixture is
      substituting for an unknown factor of considerably higher potency present in
      crude extracts. Second, we have found that a labile low-molecular-weight product
      of the 7,8-diaminopelargonic acid aminotransferase reaction stimulates the rate
      of biotin formation in the defined biotin synthase reaction mixture and can
      increase the final amount of biotin formed by threefold. This product seems to be
      derived from Ado-Met, which 7,8-diaminopelargonic acid aminotransferase uses as
      its amino donor. However, 5'-deoxy-5'-methylthioadenosine, the postulated
      breakdown product from the action of 7,8-diaminopelargonic acid aminotransferase
      on Ado-Met, cannot be the active material since it has no stimulatory effect when
      added to the biotin synthase reaction mixture. Third, with a defined reaction
      mixture in hand, [35S]cysteine and [35S]Ado-Met, two potential sulfur donors
      present in the defined reaction mixture, were tested separately as sulfur donors.
      No 35S was incorporated into newly formed biotin when either [35S]cysteine or
      [35S]Ado-Met was added to the defined biotin synthase reaction mixture.

PMID- 8579372
TI  - Synergistic interactions between vitamin A and vitamin E against lipid
      peroxidation in phosphatidylcholine liposomes.
AB  - Interactions between alpha-tocopherol and all-trans retinol in suppressing lipid
      peroxidation were studied in a unilamellar liposomal system of
      phosphatidylcholine from either egg or soybean, in which peroxidation was
      initiated by the water-soluble azo initiator 2,2-azobis(2-amidino
      propane)hydrochloride and peroxidation was measured as production of conjugated
      diene hydroperoxides. While all-trans retinol alone was poorly effective, the
      combination of all-trans retinol with alpha-tocopherol caused an inhibition
      period far beyond the sum of the inhibition periods observed with individual
      antioxidants, providing evidence of synergistic interactions. Furthermore, the
      inhibition rate calculated in the presence of both all-trans retinol and alpha
      tocopherol, Rinh(E+A), was lower than Rinh(E) observed with alpha-tocopherol
      alone, suggesting that the extension of the inhibition time cannot be ascribed
      only to the antioxidant activity of alpha-tocopherol. The extent of synergism was
      linear with a molar ratio all-trans retinol/alpha-tocopherol ranging from 0.1 to
      1.0, whereas a drop was observed at a ratio of 2.0. Synergistic antioxidant
      interactions between all-trans retinol and alpha-tocopherol were also evident
      when peroxidation was evaluated as production of malondialdehyde. A time course
      study, in which peroxidation of liposomes and depletion of antioxidants were
      concomitantly monitored, while showing that most of alpha-tocopherol was consumed
      to bring about the inhibition period, indicated that autooxidative reactions
      substantially contributed to the rapid depletion of all-trans retinol, when the
      antioxidants were allowed to act separately. On the other hand, when alpha
      tocopherol and all-trans retinol were combined, the consumption of both
      antioxidants was significantly delayed, indicating reciprocal protection.
      Regeneration mechanisms cannot be accounted for by our results. The observed
      synergism between all-trans retinol and alpha-tocopherol does not appear as the
      result of specific structural interactions in the lipid bilayer. Combination of
      all-trans retinol with butylated hydroxytoluene, which reduced markedly all-trans
      retinol oxidation, resulted in a synergistic antioxidant activity greater than
      that observed with comparable amounts of alpha-tocopherol. In light of the known
      antioxidant mechanism of retinoids, the data suggest that by limiting
      autooxidation of all-trans retinol, alpha-tocopherol strongly promotes its
      antioxidant effectiveness. The concerted radical scavenging action in turn
      results in a synergistic protection of the lipid system against peroxidative
      stress and, ultimately, slows down the alpha-tocopherol consumption.

PMID- 8579373
TI  - Characterization of Rab5:Q79L-stimulated endosome fusion.
AB  - Fusion of intracellular membrane-bound compartments is a common step in the
      transport of macromolecules along the endocytic and secretory pathways. Previous
      work has shown that GTP gamma S stimulates endosome fusion in the presence of low
      concentrations of cytosol. In this study, we have characterized the effect of
      rab5:Q79L, a mutant with reduced GTPase activity, on endosome fusion in a cell
      free assay. rab5:Q79L stimulates in vitro endosome fusion. The stimulatory
      effects required ATP, were blocked by N-ethylmaleimide (NEM) and anti-NEM
      sensitive fusion (NSF) protein antibody, but could proceed in the absence of
      cytosol. Stimulation of fusion with rab5:Q79L led to rapid inactivation of the
      vesicles when tested in a second incubation for fusogenic activity. By electron
      microscopy, endosomes connected by tubular structures were frequently observed in
      the presence of rab5:Q79L. Rab5:Q79L promoted fusion only among early endosomes;
      when the ligands were chased into more mature endocytic compartments, fusion was
      not observed. Phospholipase A2 inhibitors blocked rab5:Q79L-stimulated fusion.
      The results indicate that rab5:Q79L promotes fusion by activating factors already
      present in the membranes and that NSF and phospholipase A2 activities are
      required downstream of rab5.

PMID- 8579374
TI  - A synthetic peptidic substrate of minimal size and semioptimal sequence for the
      protein tyrosine kinase pp60c-src.
AB  - We used a novel approach to determine the minimal size and semioptimal sequence
      of a peptide to serve as an inhibitor and/or substrate for the protein tyrosine
      kinase pp60c-src. The preferred amino acids surrounding tyrosine were determined
      by a systematic study in which we increased the length of a series of linear
      peptides starting from the tripeptide EYG. Using an iterative cycle, the size of
      the peptide was increased one residue at a time, first at the amino terminus and
      then at the carboxy terminus. A series of six analogs were synthesized at each
      position and assayed as inhibitors and substrates. The amino acids G, A, L, F, E,
      and K were used to semioptimize each position. The tripeptide EYG was not a
      substrate nor an efficient inhibitor. With increasing size of the peptide, the Ki
      decreased from 10.0 to 0.10 mM. The smallest peptide to serve as a substrate was
      a hexapeptide. The best overall peptide obtained from this method, EFEYAFF, had a
      Ki value of 0.13 mM with Km and Vmax values of 0.21 mM and 680 nmol/min/mg,
      respectively. Our best peptide was found to have higher substrate specificity
      than all other commerically available peptidic substrates for pp60c-src.

PMID- 8579375
TI  - Calcium activation of mitochondrial glycerol phosphate dehydrogenase restudied.
AB  - cDNAs which encode the rat testis and pancreatic islet mitochondrial glycerol
      phosphate dehydrogenase (mGPD) (EC 1.1.99.5), the key enzyme of the glycerol
      phosphate shuttle, were recently cloned and sequenced and found to contain
      calmodulin-like calcium-binding sequences, thus explaining the widely observed
      calcium activation of the enzyme from many tissues of higher eukaryotes. mGPD
      activity and protein, as judged from Western analysis, appear to be most abundant
      in testis and pancreatic islets in the rat. mGPD is known to be located within
      the inner mitochondrial membrane. At a physiologic concentration of glycerol
      phosphate (75 microM), half maximal activity of Triton X-100-solubilized testis
      mGPD was seen in the presence of 0.1-0.25 microM free calcium. Calcium (10(-6)
      10(-5) M) lowered the Km of mGPD from 2.5 mM glycerol phosphate (islet mGPD) and
      3.2 mM glycerol phosphate (testis mGPD) to 0.4 mM glycerol phosphate. Calcium
      activation of mGPD from both testis and islets was not prevented by calmodulin
      inhibitors, which is consistent with mGPD possessing regions that can mediate its
      own activation by calcium. 45Calcium overlay experiments, in which proteins were
      separated by SDS-polyacrylamide gel electrophoresis, blotted onto nitrocellulose
      membranes, and probed with 45Ca, showed that mGPD is a major calcium-binding
      protein in testis mitochondrial membranes. A hydropathy plot suggested that the
      mature mGPD protein has three transmembrane helices. The first membrane-spanning
      region coincides with the FAD site and thus this site is placed within the
      membrane. The hydropathy analysis indicated that the calcium-binding region and
      the putative glycerol phosphate-binding site lie outside the membrane exposed to
      the cytosolic environment. This is consistent with earlier biochemical evidence
      which indicated that these sites are situated outside the membrane (M.
      Klingenberg, Eur. J. Biochem. 13, 247-252, 1970). This suggests that cytosolic
      calcium can regulate mGPD activity. Since simultaneous oscillations in electrical
      activity, cytosolic calcium, glycolysis, and insulin release occur in the
      pancreatic beta cell, mGPD activity might also fluctuate and allow the glycerol
      phosphate shuttle to participate in glycolytic oscillations.

PMID- 8579376
TI  - Functional expression of recombinant spiny dogfish shark (Squalus acanthias)
      cytochrome P450c17 (17 alpha-hydroxylase/C17,20-lyase) in yeast (Pichia
      pastoris).
AB  - The cDNA encoding the spiny dogfish shark (Squalus acanthias) testicular form of
      cytochrome P450c17 (CYP17) was used to direct the heterologous expression of a
      functional enzyme in yeast (Pichia pastoris). This protein possesses two
      enzymatic activities: 17 alpha-hydroxylase and C17,20-lyase reactions. Cytochrome
      P450c17 is a key steroidogenic enzyme for the production of sex steroids in
      gonadal tissue and for cortisol production in adrenal tissue. This study
      describes the culture conditions and the enzymatic activity of recombinant shark
      cytochrome P450c17. The shark enzyme was compatible with the endogenous yeast
      NADPH-cytochrome P450 reductase and was bioactive within the living yeast cell.
      Progesterone (at 15 microM) was metabolized (51 pmol/min/10(9) cells) faster than
      pregnenolone (36 pmol/min/10(9) cells). Both progesterone and pregnenolone were
      completely metabolized to their respective androgens (androstenedione and
      dehydroepiandrosterone). Although 11 beta-hydroxy-progesterone was readily 17
      alpha-hydroxylated by the shark P450, the lyase reaction was not evident.
      Alterations to the 2-carbon sidechain of progesterone (21-hydroxylation or 20
      beta-reduction) prevented metabolism. High-density cultures (> 1.5 x 10(9)
      cells/ml) yielded the greatest quantity of recombinant protein but cultures of
      lower density produced more recombinant protein per cell. This is the first
      report of heterologous expression in yeast of a steroidogenic cytochrome P450
      from a lower vertebrate.

PMID- 8579377
TI  - Mutagenesis study of Asp-290 in cytochrome P450 2B11 using a fusion protein with
      rat NADPH-cytochrome P450 reductase.
AB  - Asp-290 of the phenobarbital-inducible dog liver cytochrome P450 (P450) 2B11 was
      mutated to nine other amino acid residues by site-directed mutagenesis, and the
      functional significance of the unique negative charge in P450 2B11 at that
      position was studied. To facilitate the analysis of mutated P450 2B11 enzymes
      heterologously expressed in Escherichia coli, an enzymatically active fusion
      enzyme was genetically engineered between the cDNAs for P450 2B11 and rat liver
      NADPH-cytochrome P450 reductase using a Ser-Thr linker as previously described
      (Fisher et al., 1992, Proc. Natl. Acad. Sci. USA 89, 10817-10821). Sonicated
      whole-cell lysates of E. coli cells expressing the wild-type fusion protein were
      able to catalyze the 16-hydroxylation of androstenedione (AD) in the absence of
      added reductase, and exhibited activities and androstenedione metabolite profiles
      very similar to those of purified and reconstituted enzyme preparations. The
      substitution of Ala, Glu, Gly, Met, Asn, Arg, Ser, Thr, or Val for Asp-290 of
      P450 2B11 resulted in decreased AD hydroxylase activities as assessed using
      solubilized membranes. Replacement of Asp-290 with Glu yielded the highest
      activity (55% of wild type), while substituting the positively charged amino acid
      Arg created an enzyme with the lowest activity (< 1% of wild-type activity).
      Regioselectivity of AD hydroxylation was not affected although the
      stereoselectivity of hydroxylation at the 16 carbon position was altered in some
      cases. The use of the fused enzyme to study the effects of site-directed
      mutagenesis has resulted in the demonstration of the importance of size and
      charge at position 290 for enzymatic activity of P450 2B11.

PMID- 8579378
TI  - Denaturation and urea gradient gel electrophoresis of arginine kinase: evidence
      for a collapsed-state conformation.
AB  - The unfolding transition of monomeric arginine kinase from shrimp was examined in
      a multiparameter equilibrium approach. Parameters investigated included catalytic
      activity, circular dichroism, intrinsic fluorescence characteristics including
      acrylamide quenching, and steady-state anisotropy of arginine kinase derivatized
      at the reactive cysteine with fluorescent dye 5-[[[(iodoacetyl)amine]ethyl]amino]
      naphthalene-1-sulfonic acid. The time course of electrophoretic patterns in urea
      gradient gels was also determined. Midpoints of the transitions varied
      considerably depending upon the parameter, indicating the presence of populated
      intermediates. Significant unfolding began after 2 M urea with most secondary and
      tertiary structure eliminated in 5 M urea. In dilute denaturant, arginine kinase
      exhibited a small increase in specific activity and physical properties
      characteristic of a protein with collapsed structure, including an increase in
      alpha-helical content, a decrease in intrinsic fluorescence (without a shift in
      the emission maximum), an increase in anisotropy, and a decrease in fractional
      accessibility by tryptophan to acrylamide quenching. The electrophoretic pattern
      of arginine kinase in urea gradient gels is consistent with the presence of a
      compact conformation in dilute denaturant. The results indicate the existence of
      a contracted overall conformation in dilute urea. The persistence of catalytic
      activity suggests this structure may be a functional molecular isoform, but the
      obvious differences in structure between the native state and the conformation of
      arginine kinase in 0.5 M urea raise the question of whether such isoforms may
      also be a type of folding intermediate.

PMID- 8579379
TI  - Liver microsomal levels of cytochrome P450IA1 as biomarker for exposure and
      bioavailability of soil-bound polycyclic aromatic hydrocarbons.
AB  - The bioavailability of soil-bound polycyclic aromatic hydrocarbons (PAHs) for
      mammalian species was studied with rats fed with a diet containing contaminated
      soil preparations. The extent of cytochrome P450IA1 (CYP1A1) induction in the
      liver correlated with the amount of 5- and 6-ring PAHs in the soil samples but
      not with the total PAH content. Other cytochromes P450 were much less affected by
      the soil-contaminants. The highest induction of CYP1A1 was obtained with a sample
      containing 274 mg 5- and 6-ring PAH/kg soil, resulting in a nearly 360-fold
      increase in the ethoxyresorufin deethylase (EROD) activity. In a semilogarithmic
      plot, a linear correlation was found between the 5- and 6-ring PAH concentration
      in the soil and the microsomal CYP1A1 content. As a model for the action of
      intestinal fluids, soil samples were extracted by bile acid solution. In these
      experiments, the selectivity in the solubilization of individual PAHs parallels
      that of toluene extraction, although the yield is lower than the latter and
      varies with the soil sample. The bioavailability of PAHs for microorganisms, but
      not for mammals, was shown to be considerably reduced in the presence of high
      total organic carbon (TOC) values of the soil samples. This may have implications
      for decontamination strategies, diminishing the effectiveness of biological
      decontamination in cases with high TOC values. The data suggest that CYP1A1
      induction in rats is a parameter that may be useful in risk assessments of
      contaminated soils for mammalian species.

PMID- 8579380
TI  - Habitual and genetic factors that affect urinary background levels of biomarkers
      for organic solvent exposure.
AB  - Urinary hippuric acid, phenol, and o-cresol, which are biomarkers for toluene,
      benzene, and phenol exposures, are usually present in a significant amount in
      urine collected from subjects who have not been occupationally exposed to the
      organic solvents. With the improvement of working environments, the urinary
      concentrations of the biomarkers have become lower and closer to the levels of
      urine from unexposed subjects. It is very useful to clarify the background levels
      of these biomarkers and the factors which effect the background levels of the
      biomarkers in order to make effective use of biological monitoring under low
      level exposure. In the present study, the effects of life habits and the genetic
      polymorphisms of the metabolizing enzymes on the background levels of urinary
      hippuric acid, phenol and o- and p-cresol were clarified, using 351 males (means
      age: 38.6, range: 19-71) who were not occupationally exposed to hazardous
      chemical materials. Their life habits, smoking, alcohol consumption, and dietary
      habits were examined by means of a questionnaire. The genotypes of five
      metabolizing enzymes, that is, low Km aldehyde dehydrogenase (ALDH2), polymorphic
      N-acetyl transferase (NAT2), cytochrome P-4501A1 (CYP1A1), cytochrome P-4502E1
      (CYP2E1), and glutathione-S-transferase mu (GSTM1) were determined form
      peripheral blood samples. The urinary hippuric acid and creatinine were analyzed
      by HPLC and urinary phenol, o-, p- and m-cresol were determined by GC/MS.
      Recoveries and the coefficients of variance of phenol, o-cresol, and p-cresol
      ranged from 92.7 to 107.8% and 1.3% to 6.7%, respectively. Linear relationships
      between the concentrations of phenol, o- and p-cresol, and their peak area ratios
      were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579381
TI  - Background exposure of general population to cadmium and lead in Tainan city,
      Taiwan.
AB  - Venous blood samples, 24-h total food duplicate samples, and rice samples were
      collected from 52 adult non-smoking women in the city of Tainan, southern Taiwan,
      in 1994, and analyzed for cadmium (Cd) and lead (Pb) by wet-digestion followed by
      graphite furnace atomic absorption spectrophotometry. Daily dietary intake was 10
      micrograms for Cd and 22 micrograms for Pb as geometric means, of which Cd and Pb
      in rice accounted for 34% and 1.4% of daily Cd and Pb intakes, respectively. The
      counterpart values for blood were 1.11 ng/ml and 44.5 ng/ml for Cd and Pb,
      respectively. International comparison with recently published data suggests that
      the exposure to Cd in Tainan should be among the lowest in the world.

PMID- 8579382
TI  - Handwipe sampling and analysis procedure for the measurement of dermal contact
      with pesticides.
AB  - A handwipe sampling and analysis procedure was developed for the measurement of
      dermal contact to pesticides. This procedure utilizes cellulose dressing sponges
      wetted with 2-propanol. A two-step wiping procedure is described that ensures
      that the entire hand is sampled. Removal efficiency experiments show that dry
      residues of the pesticides chlorpyrifos and pyrethrin I are quantitatively
      removed from hands immediately following contact. Results suggest that the
      procedure may remove pesticide residues that are deeply embedded in the skin and
      not removed by soap-and-water washing. Extraction efficiency studies for 29 other
      pesticides show that the proposed extraction method may be applicable for a wide
      range of pesticides including phenoxy-acid herbicides. Field testing of the
      procedure indicates that it is easily implemented by sampling personnel and
      readily accepted by children.

PMID- 8579383
TI  - The role of DDE and polychlorinated biphenyl levels in preterm birth.
AB  - Maternal serum levels of DDE and polychlorinated biphenyls (PCB) and their
      congeners were compared for 20 women who had a spontaneous preterm delivery and
      20 matched women who had delivered at term at Mount Sinai Medical Center in New
      York between October 1990 and August 1993. Since no substantial case-control
      differences were evident, these findings do not indicate that increased DDE or
      PCB levels are associated with spontaneous preterm birth.

PMID- 8579384
TI  - Analytical characterization of peptide contaminants of L-tryptophan.
AB  - Reversed-phase liquid chromatographic fractions of extracts of 2 preparations of
      eosinophilia-myalgia syndrome (EMS)-associated L-tryptophan were analyzed by
      proton nuclear magnetic resonance spectrometry, mass spectrometry, microbial
      growth inhibition, and amino acid residue analyses. Fraction components
      demonstrated properties of an antibiotic peptide resembling bacitracin. Many
      peptide antibiotics like bacitracin are secondary metabolites of Bacillus
      species, genus of the tryptophan producer organism for the implicated
      manufacturer. In order to determine whether a correlation exists between
      individual EMS cases and the concentration of peptides or bacitracin consumed,
      reliable methods must be developed for quantification of the total of isoforms.

PMID- 8579385
TI  - Organochlorine residues in tissues of striped dolphins affected by the 1990
      Mediterranean epizootic: relationships with the fatty acid composition.
AB  - A simple and rapid method was developed for the simultaneous determination of
      fatty acids, organochlorine pesticides, and polychlorinated biphenyl (PCB)
      congeners in the same sample in order to explore possible connections between
      levels of contaminants and fatty acid composition. The method was applied to
      samples of melon, cerebrum, cerebellum, lung, liver, kidneys, and skeletal muscle
      obtained from 5 male and 5 female striped dolphins (Stenella coeruleoalba) found
      stranded in 1990 in the northeastern Spanish coasts during the morbillivirus
      epizootic that affected this cetacean in the Mediterranean Sea. The results
      indicate that PCBs were dominant in all tissues, with the highest geometric mean
      concentration being found in melon (903 micrograms g-1 wet wt); sigma DDTs were
      also found at high concentrations (111 micrograms g-1 wet wt, in melon).
      Statistical analysis indicate that organochlorine concentration was correlated
      with the fatty acid composition of tissues, although some of these variations can
      be interpreted as a consequence of a shift in the diet produced in the striped
      dolphin population. However, other changes such as the negative correlation with
      arachidonic acid may suggest that the eicosanoid production could have been
      affected by the extremely high concentrations of PCBs and sigma DDTs.

PMID- 8579386
TI  - Toxicity of seleno-L-methionine, seleno-DL-methionine, high selenium wheat, and
      selenized yeast to mallard ducklings.
AB  - The toxicity of four chemical forms of selenium (seleno-L-methionine, seleno-DL
      methionine, selenized yeast, and high selenium wheat) was compared in day-old
      mallard ducklings (Anas platyrhynchos). In the first experiment, in which the
      basal diet was 75% wheat, survival after 2 weeks was lower for ducklings fed 30
      micrograms/g selenium as seleno-L-methionine (36%) than for ducklings fed 30
      micrograms/g selenium as seleno-DL-methionine (100%) or 30 micrograms/g selenium
      from high selenium yeast (88%). The concentration of selenium at 2 weeks in the
      livers of survivors was similar for ducklings fed 15 micrograms/g selenium as
      seleno-DL-methionine (12 micrograms/g, wet weight), seleno-L-methionine (11
      micrograms/g), and high selenium wheat (11 micrograms/g), but was lower when the
      selenium came from selenized yeast (6.2 micrograms/g). When fed 30 micrograms/g
      selenium from the various sources, the selenium concentrations in liver were 20
      micrograms/g for seleno-DL-methionine, 19 micrograms/g for seleno-L-methionine,
      and 9.9 micrograms/g for selenized yeast. In a second experiment, in which the
      basal diet was a commercial duck feed, survival after 2 weeks was 100% in
      ducklings fed 30 micrograms/g selenium as seleno-DL-methionine, seleno-L
      methionine, or selenized yeast. Selenium concentrations in liver were similar for
      ducklings fed the 30-micrograms/g selenium diets as the DL or L forms of
      selenomethionine (27 and 25 micrograms/g), but lower for ducklings fed selenized
      yeast (13 micrograms/g).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579387
TI  - [2 lives--claims and reality: an expanded edition of the opening address at the
      23 August 1994 Congress].

PMID- 8579388
TI  - [Contra endoscopic ovarian surgery].

PMID- 8579389
TI  - [Environmental pollutants in ovarian cysts].

PMID- 8579390
TI  - [Consequences of the public health structure law for naturopathic methods in
      gynecology].

PMID- 8579391
TI  - [Sense and success of psychosomatic preparation for labor].

PMID- 8579392
TI  - [Drugs for labor pain].

PMID- 8579393
TI  - [Development and clinical concept of "natural childbirth" exemplified by the
      Bensberg Gynecology Clinic of the Vinzenz-Pallotti Hospital].

PMID- 8579394
TI  - [Ambulatory endoscopic surgery--ovary and leiomyoma].

PMID- 8579395
TI  - [[Initial results of "preventive self-care by pregnant patients" for prevention
      of premature labor].

PMID- 8579396
TI  - [Prenatal diagnosis--current aspects].

PMID- 8579397
TI  - [Contribution to the discussion of quality assurance measures in ambulatory
      surgery].

PMID- 8579398
TI  - [Maternal cesarean section mortality--a critical evaluation].

PMID- 8579399
TI  - [Hysteroscopic surgery].

PMID- 8579400
TI  - [Environment and hospital].

PMID- 8579401
TI  - [Environment and oncology].

PMID- 8579403
TI  - [Environment and industry].

PMID- 8579402
TI  - [Environment and reproduction].

PMID- 8579404
TI  - [Quality of life--attempt at a definition of the concept].

PMID- 8579405
TI  - [Surgical oncology and quality of life].

PMID- 8579406
TI  - [Psycho-oncology in gynecology].

PMID- 8579407
TI  - [Oncologic after-care and rehabilitation--physician-patient interaction in
      gynecologic oncology].

PMID- 8579408
TI  - [The cancer patient between academic medicine and alternative medicine-
      therapeutic concepts].

PMID- 8579409
TI  - [Endoscopic surgery and malpractice].

PMID- 8579410
TI  - [Statistics and quality assurance in endoscopic fallopian tube surgery].

PMID- 8579411
TI  - [Pro and contra: pelviscopy and microsurgery of the fallopian tube].

PMID- 8579413
TI  - [Pro: a critical contribution to better understanding of possible functional
      disorders of the genital, bladder and pelvic floor system].

PMID- 8579412
TI  - [Current aspects of diagnosis and therapy of tubal sterility].

PMID- 8579414
TI  - [Endoscopic surgery and quality--graduate education and educators].

PMID- 8579415
TI  - [Contra cervix extirpation].

PMID- 8579416
TI  - [Decision paths and foundation of the Karlsruhe verdict].

PMID- 8579417
TI  - [Reform of section 218 StGB reform--analysis of parliamentary decision].

PMID- 8579418
TI  - [Counseling as procedural model for illegal, but not punishable abortion].

PMID- 8579419
TI  - [Twins and multiple pregnancy].

PMID- 8579420
TI  - [General aspects of endoscopic surgery--endoscopic hysterectomy].

PMID- 8579421
TI  - [Parameters for risk assessment and risk prevention in pregnancy].

PMID- 8579422
TI  - [Dialogue between oncology and molecular biology].

PMID- 8579423
TI  - [Endocrinology and immunology in reproduction medicine].

PMID- 8579424
TI  - [The value of colposcopy in assessment of intraepithelial neoplasia of the lower
      genital tract].

PMID- 8579425
TI  - [Minimally invasive surgery and quality. Meeting report].

PMID- 8579426
TI  - [Premature labor and its limits. Introduction].

PMID- 8579427
TI  - [Prevention of infection and therapy of premature labor].

PMID- 8579428
TI  - [Therapy of threatened premature labor].

PMID- 8579429
TI  - [Characteristics of delivery of the small premature infant].

PMID- 8579430
TI  - [Fetal death and complications in premature infants today].

PMID- 8579432
TI  - [Prenatal diagnosis as ethical problem field].

PMID- 8579431
TI  - [Long-term prognosis of very small premature infants].

PMID- 8579433
TI  - [Abortion as experienced by the physician in charge--attitudes in the conflict
      area of abortion].

PMID- 8579434
TI  - [Pro home delivery].

PMID- 8579435
TI  - [Contra home delivery].

PMID- 8579436
TI  - [Natural family planning].

PMID- 8579437
TI  - [Intrauterine devices].

PMID- 8579438
TI  - [Oral contraception--benefits and risks].

PMID- 8579439
TI  - [Depot gestagens].

PMID- 8579440
TI  - [Future prospects in contraception].

PMID- 8579441
TI  - [Immunology and oncology].

PMID- 8579442
TI  - [Anesthesiology and intensive care medicine in geriatric gynecologic surgery].

PMID- 8579443
TI  - [Women see--women physicians--see women].

PMID- 8579444
TI  - [Psychosocial stresses of gynecologists and their effects].

PMID- 8579445
TI  - [Gynecologist--an occupation incompatible with family life?].

PMID- 8579446
TI  - [The hospital--requirements and reality].

PMID- 8579447
TI  - [Women's health--a global challenge].

PMID- 8579448
TI  - [Psycho-oncology].

PMID- 8579449
TI  - [Assisted reproduction--new developments].

PMID- 8579450
TI  - [Natural family planning in the physician's office--cooperation with specialized
      counselors].

PMID- 8579451
TI  - [Electronic data processing in the physician's practice].

PMID- 8579452
TI  - [Educational goals in surgical gynecology in Europe].

PMID- 8579453
TI  - [Geriatric surgery in gynecology].

PMID- 8579454
TI  - [The status of German gynecology in Europe].

PMID- 8579455
TI  - [Characteristics of career and life planning by women physicians].

PMID- 8579456
TI  - [Psychological and social career blocks in the career path of the woman
      physician].

PMID- 8579457
TI  - [Women physicians and academic careers].

PMID- 8579458
TI  - [Woman physician in general practice].

PMID- 8579459
TI  - [Medical education of women in Germany--progress in our century].

PMID- 8579460
TI  - [Cooperation, community practice and practice community].

PMID- 8579461
TI  - Allocation of intensive care resources.

PMID- 8579462
TI  - [Rationalization instead of rationing: can GKV have solidarity and efficiency at
      the same time?].

PMID- 8579463
TI  - [Marketing and teamwork in gynecologic practice].

PMID- 8579464
TI  - [The DGGG project "Quality assurance in surgical gynecology].

PMID- 8579465
TI  - [Quality assurance in surgical gynecology--10 years experiences].

PMID- 8579466
TI  - [Gynecology in national socialism--or "the late apology"].

PMID- 8579467
TI  - [The current and future age structure of women in our society].

PMID- 8579468
TI  - [Gonadotropins and infertility--a historical overview].

PMID- 8579469
TI  - [Pro endoscopic ovarian surgery].

PMID- 8579470
TI  - Chemotaction of mouse spermatozoa induced by certain hormones.
AB  - Chemotaxis assays of mouse spermatozoa were performed in vitro. Amounts of
      calcitonin (5.0 IU/ml, 10.0 IU/mL) and acetylcholine (1.0 mg/ml) in Biggers
      Whitter-Whittingham medium filled out wells of experimental plate were increased
      directly by migration of mouse spermatozoa to the medium containing these
      hormones. This effect was interpreted as chemotaxis of spermatozoa. Low
      concentrations of hormones were not attractants and high concentrations of
      acetylcholine (5.0 mg/mL) decreased spermatozoa migration. Glucagon and
      vasopressin results in a decrease in concentration of migrated spermatozoa. In
      low concentrations of these hormones differences in sperm migration were not
      observed. Presence of histamine and thyroxine in BWW medium did not affect the
      migration behavior of mouse spermatozoa in vitro.

PMID- 8579471
TI  - Sperm select penetration test reveals differences in sperm quality in strains
      with different Y chromosome genotype in mice.
AB  - Mouse sperm penetration into a hyaluronic acid polymer (Sperm Select),
      hypoosmotic swelling in distilled water (water test), and eosin-Y staining were
      studied in sperm samples from males belonging to five inbred strains of mice
      (CBA, KE, KE-YCBA, B10.BR, and B10.BR-Ydel), which differ in the proportion of
      abnormal sperm heads and in efficiency of fertilization. Correlation
      coefficients, calculated from mean values for each strain, showed that Sperm
      Select penetration (to the depth of 1-2 cm) was significantly correlated with
      both sperm motility and fertilization efficiency, while correlation with the
      proportion of normal spermatozoa did not reach the level of significance. The
      indices of the water test and erosin Y staining were correlated with each other
      but not with Sperm Select penetration. In comparison with the B10.BR strain, its
      mutant strain B10.BR-Ydel, with a large deletion in the long arm of the Y
      chromosome and characterized by highly elevated proportion of abnormal sperm and
      low fertilization efficiency, showed lower values of the indices of all tests,
      suggesting that the partial deletion of the Y chromosome has affected various
      aspects of sperm morphology and function. On the other hand, for two consomic
      strains (KE and KE-YCBA with the Y chromosome introduced from the CBA strain),
      the difference in sperm morphology and fertilization rate was correlated with
      Sperm Select penetration but not with hypoosmotic swelling or eosin-Y staining;
      this suggests that only some aspects of sperm physiology are due to genetic
      differences between YKE and YCBA chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579472
TI  - Effect of castration on metalloprotease activities in the lateral, dorsal, and
      anterior lobes of the rat prostate.
AB  - Several proteolytic enzymes are involved in mediating the regression of the
      prostate gland following castration. A previous study showed that plasminogen
      activator activities are elevated only in the ventral lobe by castration in the
      rat. Since matrix metalloproteases represent a different class of protease that
      degrade extracellular matrix, this study examined their activities in the
      lateral, dorsal, and anterior lobes of the rat in response to androgen
      deprivation. The results indicate that, in contrast to plasminogen activators,
      metalloprotease activities are increased in the lateral, dorsal, and anterior
      lobes following orchiectomy. This suggests that differences in regulation of
      certain proteases by androgens may occur in individual prostatic lobes.

PMID- 8579473
TI  - Aromatization of [4-14C]testosterone to [14C]estradiol-17 beta by testicular
      tissue from male-to-female transsexuals on estrogen therapy.
AB  - Abnormality in testicular biosynthesis of sex hormones may accompany or cause
      transsexualism. With a view to determine whether the cells of male transsexual
      testicular tissue possess aromatic cytochrome P-450 activity, homogenates of the
      tissue from 4 phenotypic male-to-female transsexuals (2 Chinese and 2 Malays,
      aged 23-34 years) with XY karyotype who had been on estrogen therapy for 9-17
      years until orchidectomy were incubated with [4-14C]testosterone as substrate.
      Using reverse-isotope dilution analysis, identity was established for
      [14C]estradiol-17 beta. No such metabolite was found in parallel incubations of
      heat-denatured enzymes. The extent of enzyme-catalyzed conversion was 9.3 x 10(
      3) to 3.4 x 10(-2)%. The specific biosynthetic aromatase cytochrome P-450
      activity contained in the tissue system can synthesize [14C]estradiol-17 beta
      from [4-14C]testosterone. Elevated aromatic expression in situ may have important
      effects on target tissues.

PMID- 8579474
TI  - Intrauterine insemination for cervical and male factor without superovulation.
AB  - Intrauterine insemination (IUI) has been used for the treatment of various causes
      of infertility, including unexplained infertility, male factor, and cervical
      factor. Some centers frequently use superovulation combined with IUI. The study
      presented herein attempted to evaluate the efficacy of IUI without superovulation
      in cases where all causes of infertility other than cervical or male factors have
      been eliminated. However, in the case of poor or absent cervical mucus, the use
      of controlled ovarian hyperstimulation (COH) may obscure the actual importance of
      the IUI, since it is possible that the poor cervical mucus is related to poor
      timing, inadequate follicular maturation, or low estradiol levels, which if
      corrected will obviate the need for IUI. In this study IUI was targeted for 36-40
      h following the sera luteinizing hormone surge. A total of 108 patients were
      enrolled in this study: 47 with male factor, 61 with cervical factor. Patients
      were followed for a maximum of three cycles unless a pregnancy occurred within 3
      months of treatment. Comparison of pregnancy rates (PRs) were based on diagnosis.
      The cumulative PRs per cycle for each of the three cycles studied were as
      follows: cervical factor--19.7, 36.8, and 36.8%; male factor--12.8, 29.3, and
      38.3%. Thus, PRs were comparable for both groups after three treatment cycles.
      These data demonstrate that IUI is an effective therapy for cervical and/or male
      factor, even without superovulation.

PMID- 8579475
TI  - Effect of varicocele on fertility potential: comparison between impregnating and
      nonimpregnating groups.
AB  - Sixty patients with varicocele, complaining of infertility, underwent a
      corrective operation. Eighteen (30%) of the 60 patients impregnated their mates
      (impregnating group). Sperm concentration significantly increased after the
      operation in the impregnating group (p < .05), but not in the patients who failed
      to impregnate their mates (nonimpregnating group). Sperm motility was not altered
      after the operation in these two groups. Sperm velocity significantly increased
      postoperatively in the impregnating group (p < .05), while linearity was not
      altered in either group. Sperm swelling significantly increased postoperatively
      in the impregnating group (p < .05), but not in the nonimpregnating group.
      Preoperative sperm parameters were not different between the two groups.
      Varicocele may disturb sperm function including sperm motion besides
      spermatogenesis and may impair the fertility potential. However, a prospective
      large-scale controlled study is required to obtain a definitive conclusion.

PMID- 8579476
TI  - Treatment with thymosin alpha-1 increases fertilizing capacity of sperm of
      infertile men: a multicenter trial.
AB  - Thymosin alpha-1 (T alpha 1) significantly enhances the fertilizability of sperm
      from fertile men by increasing capacitation and/or acrosome reaction. The present
      study was conducted to investigate the effect of T alpha 1 on fertilizing
      capacity of sperm of infertile men using the sperm penetration assay (SPA) in a
      multicenter clinical trial. T alpha 1 significantly (p = .0006 to < .0001)
      increased (31 to 45%) fertilizing capacity of sperm of 76% (50/68) of infertile
      men as defined by the sperm penetration index in SPA. The enhancing effect of T
      alpha 1 and the degree of enhancement depended on the T alpha 1 concentration in
      the seminal plasma, since these parameters showed a significant intercorrelation
      (r = .65 to .74, p = .039 to .01). It would appear that T alpha 1 may have
      clinical application in the diagnosis and treatment of male infertility
      especially mediated through defective sperm function.

PMID- 8579477
TI  - Alpha-1,4-glucosidase activity and the presence of germinal epithelium cells in
      the semen for differential diagnosis of obstructive and nonobstructive
      azoospermia.
AB  - Among azoospermics, the activity of seminal alpha-glucosidase (alpha G) is low in
      obstruction (OBS) cases, but there is no agreement regarding its value in others.
      With the hypothesis that a more marked decrease in alpha G activity occurs in OBS
      than in spermatogenesis arrest (SA), the enzyme was measured in the following
      groups: (1) vasectomized males (n = 15), (2) azoospermics with OBS (n = 7), (3)
      azoospermics with SA (n = 11), and (4) fertile males (n = 15). Patients within
      groups 2 and 3 had a testicular volume > or = 15 mL, no clinical evidence of
      abnormal epididymis, normal serum gonadotropins, and histological diagnosis.
      alpha G activities (mU/g protein, means +/- SD) by group were (1) 131 +/- 60, (2)
      312 +/- 186, (3) 728 +/- 303, and (4) 1176 +/- 374. All between-group differences
      were significant (t test, p < .01), except for groups 1 vs. 2 comparison (.05 > p
      > .01). These results support the notion that SA is associated with a decrease in
      alpha G that is less marked that seen in OBS. The search for germinal epithelium
      cells in semen also allows discrimination between these two azoospermic groups.

PMID- 8579478
TI  - Relationship between intracellular calcium, energy metabolism, and motility of
      ram sperm.
AB  - Collective sperm motility is characterized in terms of periodic aggregation or
      cooperation among cells, which are seen under a microscope as a continuous wave
      motion. In this study, sperm motility that was made dependent on mitochondrial
      activity (glycolysis inhibited) was significantly inhibited by mM exogenous
      calcium while glycolytic-dependent (mitochondrial respiration inhibited) motility
      was not inhibited under these conditions. At intracellular Ca2+ above 400 nM,
      sperm motility was inhibited independently of the source of ATP. At [Ca2+]i of
      approximately 110 nM, mitochondrial- or glycomitochondrial-dependent motility
      showed 75 or 0% inhibition, respectively, indicating higher sensitivity of
      mitochondrial-dependent motility to [Ca2+]i in comparison to glycolytic-dependent
      motility. Under the latter conditions, intracellular level of ATP was reduced by
      16% only, indicating that the 75% inhibition of mitochondrial-dependent motility
      was not due to reduction in ATP. The inhibition of mitochondrial-dependent
      motility by mM extracellular Ca2+ can be prevented by incubating the cells at pH
      6.5 instead of 7.6. At pH 7.6, calcium probably interacts with negative sites on
      the cell surface and interferes in cell-to-cell interactions, which are important
      to achieve collective motility. At more acidic pH (6.5) these negative sites are
      probably protonated; thus Ca2+ cannot interact with them and no inhibition of
      motility could be seen. Glycolytic-dependent motility was not inhibited by
      extracellular Ca2+, since the pH of the medium becomes acidic under these
      conditions. Like Ca2+, mersalyl, which interacts with Ca2+ binding sites on the
      cell surface, showed significant inhibition of mitochondrial-dependent motility
      without any effect on glycolytic-dependent motility. Collective motility was
      directly correlated with fertility. These data are significant for establishing
      better conditions for spermatozoa treatment when artificial insemination or in
      vitro fertilization is concerned.

PMID- 8579480
TI  - [Progress of allergology and cell reaction--recognition of adult onset
      intractable asthma].

PMID- 8579479
TI  - Histopathology of the seminiferous tubules in mice injected with syngeneic
      testicular germ cells alone.
AB  - Previously, a model of murine experimental autoimmune orchitis was produced by
      active immunization with viable syngeneic testicular germ cells without resorting
      to any adjuvants. The histological mode of the spermatogenic disturbance of this
      autoimmunity was investigated in A/J mice. A significant spermatogenic
      disturbance was consistently induced after the appearance of inflammatory cell
      responses around the tubuli recti. It first appeared seminiferous epithelium
      adjacent to the tubuli recti, then spread to the peripheral epithelium. The
      histopathology of the seminiferous tubules in the early phase ranged from partial
      degeneration and depletion of all kinds of germ cells to complete loss of germ
      cells other than some remaining spermatogonia, while both Sertoli cells and the
      basal lamina of the tubules appeared intact. In the late phase, depletion of
      Sertoli cells, disorganization of the seminiferous tubular wall or filling with
      many round-shaped degenerating germ cells, appearance of malformed spermatids
      with signet ring nuclei, depletion of immature germ cells with remaining
      elongated spermatids, or complete loss of the seminiferous epithelium were
      observed in addition to the early histopathological features.

PMID- 8579481
TI  - [Chronological analysis of eosinophil infiltration in mite-allergen induced
      dermatitis in atopic patients].
AB  - To elucidate the active process of eosinophil infiltration in atopic dermatitis
      (AD), we performed patch testing using crude mite allergens on normal-appearing
      skin in adult AD patients with high levels of mite-specific IgE antibodies and
      analyzed positive reaction sites chronologically by histological and
      immunohistological methods. Positive reactions were observed in 6 out of 9 AD
      patients (66.7%), whereas none of 7 non-AD control subjects showed positive
      reactions. Skin biopsies were obtained from positive reaction sites at 2,6,12,24
      and 48 hours after allergen challenge. Eosinophils were seen within postcapillary
      venules at 2 hours, followed by increased perivascular eosinophil infiltration at
      6 hours which peaked at 24 and 48 hours. Epidermal eosinophilic spongiosis was
      also observed at 48 hours. The majority of infiltrating eosinophils showed
      positive reactions for BMK-13 and 15-59% of them were EG2 positive activated
      eosinophils. BMK-13, EG2 and anti-EP positive reactions were scattered throughout
      connective tissue and their areas were time-dependently increased. These findings
      suggest that eosinophil transmigration and activation play an important role in
      initiating early AD lesions induced by transepidermal mite allergen permeation.

PMID- 8579482
TI  - [Study of cockroach allergy in asthmatic children. The positive rates and
      antigenicity of cockroach allergen].
AB  - The specific IgE antibodies to 4 species of cockroach were measured in sera from
      51 asthmatic children 6 to 16 years old by RAST and CAP system. Positive rates of
      RAST to Periplaneta fuliginosa, Blattela germanica, Periplaneta americana and
      Periplaneta japonica were 17.6%, 29.4%, 19.6% and 15.7%, respectively and those
      of CAP system to Periplaneta fuliginosa and Blattela germanica were 15.7%,
      respectively. Among those with positive RAST to 4 species of cockroach there were
      significant correlations. Significant correlations were observed also between the
      RAST titer for the whole bodies and feces of Periplaneta fuliginosa and Blattela
      germanica and immunoblotting analysis of sera obtained from two cockroach
      positive patients revealed common sensitive fraction between whole body and
      feces. Immediate bronchial response was detected by bronchial provocation test.
      RAST inhibition study indicated no cross-reacting allergenicity between cockroach
      and mite. Collectively, cockroach is one of important inhalent allergens in
      asthmatic children.

PMID- 8579483
TI  - [Generation of tumor necrosis factor alpha by human nasal epithelial cells and
      inhibition by fluticasone propionate].
AB  - Accumulation of mast cells and eosinophils in the nasal epithelial layer occurs
      in nasal allergic reaction, However, the mechanism of accumulation of these cells
      has not yet been well clarified. We hypothesized that cytokines generated from
      the nasal epithelial cells contributed to the accumulation of these cells in the
      nasal epithelial layer. Recently tumor necrosis factor (TNF) was shown to promote
      polymorphonuclear neutrophils and eosinophils migration. And also TNF increased
      eosinophil binding to vascular endothelial cells. In this in vitro study we
      examined whether or not nasal epithelial cells can produce TNF-alpha and also
      whether or not glucocorticosteroid fluticasone propionate (FP) can modulate TNF
      alpha production from nasal epithelial cells. Nasal epithelial cells
      constitutively produce TNF-alpha in accordance with the nasal epithelial cells'
      number and this was substantially increased in the state of nasal epithelial
      cell's proliferating. FP significantly reduced the level of TNF-alpha in the
      supernatant of cultured nasal epithelial cells for a period of 6 days. In
      addition, preincubation of nasal epithelial cells with FP for 6 days caused
      significant reduction of TNF-alpha level in the supernatant of cultured nasal
      epithelial cells during a further period of 6 days without FP. These data support
      the concept that structural cells play an active role in the control of allergic
      and related inflammatory processes.

PMID- 8579484
TI  - [Suppressed increase of C3 receptors on polymorphonuclear leukocytes by
      stimulation with C5a in diabetes mellitus].
AB  - This study was undertaken to clarify the susceptibility to infection of patients
      with diabetes mellitus. The complement system is activated through the classical
      and/or the alternative pathways to produce many kinds of anaphylatoxins in the
      inflammatory process. One of the anaphylatoxins, C5a, possesses both the strong
      biological activity of a chemotactic factor and the increasing effect of CR1 and
      CR3 expression on polymorphonuclear leukocytes (PMNs). It is well known that the
      complement receptors, CR1 and CR3, on PMNs play important roles in the
      phagocytosis. We studied the changes of the expression of these receptors on PMNs
      in non-insulin dependent diabetes mellitus after the stimulation with recombinant
      human C5a. PMNs from 11 patients with non-insulin dependent diabetes mellitus and
      11 normal controls were tested. There was no significant difference of CR1 and
      CR3 expression on PMNs after the addition of 10 ng/ml C5a between patients with
      diabetes mellitus and normal controls. However, by the stimulation with 50 ng/ml
      C5a, the increase of the CR3 expression on PMNs of patients with diabetes
      mellitus was significantly smaller than normal controls (p < 0.02). The increase
      of the expression of CR1 on PMNs was not significantly different the two groups.
      It is suggested that the small increase of the CR3 expression on PMNs by the
      stimulation with C5a is one of the factors of the susceptibility to infection in
      patients with diabetes mellitus.

PMID- 8579485
TI  - [The effect of KW-4679, an antiallergic drug, on experimental allergic rhinitis].
AB  - Effect of KW-4679, an antiallergic agent, on the experimental allergic rhinitis
      was studied in guinea pigs. 1) KW-4679 inhibited the sneeze response and the
      nasal rubbing induced after the intranasal administration of antigen in
      sensitized guinea pigs. The inhibitions were dose-related and significant at 0.03
      mg/kg p.o. for sneeze response and 1 mg/kg p.o. for nasal rubbing, respectively.
      2) The nasal vascular permeability was increased after the intranasal
      administration of antigen in sensitized guinea pigs. KW-4679 significantly
      reduced the increase of the nasal vascular permeability at 1 mg/kg p.o. or
      higher. From these results, KW-4679 may have inhibitory effects on sneeze, nasal
      irritation and rhinorrhea in clinical use.

PMID- 8579486
TI  - [Effects of mao-bushi-saishin-to (MBST) on experimental allergic models in rats].
AB  - Effects of oral administration of MBST on 48 hr homologous passive cutaneous
      anaphylaxis (PCA) and allergic rhinitis in rats were examined. Administration of
      MBST (1,000 mg/kg/day) for 5 consecutive days with the final dosing at 1 day
      before antigen challenge did not effect on PCA. However, the reaction was
      significantly inhibited when the drug (1,000 mg/kg) was singly given 1 hr before
      antigen challenge. The drug (1,000 mg/kg, 1 hr prior to antigen challenge) tended
      to reduce the dye leakage into nasal cavities by antigen, while it did not affect
      on the anaphylactic histamine release into the cavities. The component of the
      chinese plants in the formula inhibiting the dye leakage was found to be Mao.
      However, l-ephedrine and d-pseudoephedrine, which are contained in Mao in a large
      amount, did not contribute to the inhibiting effect on dye leakage. These results
      suggest that MBST may be therapeutically effective for atopic disease including
      rhinitis, through the mechanism other than the inhibition of histamine release.

PMID- 8579487
TI  - [A case of eosinophilic pneumonia mimicking hypereosinophilic syndrome, which
      improved spontaneously].

PMID- 8579489
TI  - [Immunoblastic lymphadenitis: pathohistologic picture and differential diagnosis
      from malignant lymphoma].
AB  - Immunoblastic lymphadenitis is a T-cell immune hyper-response to antigenic
      stimulation. Patho-histologically, polymorphic hyperplasia of the lymph node pulp
      with a widening of the paracortical zone and the disturbance of the node
      structure is found. The cells of the paracortical proliferate are represented by
      small lymphocytes, stimulated lymphoid cells of varying size with numerous
      immunoblasts, plasma cells at various stages of maturation including
      lymphoplasmocytoid ones. When the structure of the lymph node is disturbed
      immunohistochemical examination is necessary to reject malignant lymphoma.

PMID- 8579488
TI  - [Malignant neoplasms of the peripheral nerve sheaths with cellular
      immunophenotype of perineural cells (perineural sarcoma?)].
AB  - 2 cases of soft tissue malignant tumors formally related to the group of spindle
      cell sarcoma are described. The majority of cells expressed an epithelial
      membranous antigen and vimentin but were S-100 protein unreactive, i.e. had a
      phenotype characteristic of perineural cells. Monoclonal antibodies to 5 types of
      filaments protein of intermediate type, neurone specific enolase and collagen
      type I, II, III, IV, V were also used as well as electron microscopic
      investigation. Problems of differential diagnosis from schwannomas,
      fibrosarcomas, monophasic spindle cell "synovial sarcoma" and validity of
      integrating these tumors into an independent variety of malignant peripheral
      nerve sheath tumors are discussed.

PMID- 8579491
TI  - [Remembrance of Nicolai Aleksandrovich Kraevskii (on his 90th birthday)].

PMID- 8579490
TI  - [Prostaglandins of series E in morphologic variants of osteogenic sarcoma and
      evaluation of the degree of therapeutic pathomorphism of the tumor].
AB  - The content of prostaglandins E (PGE) is studied in osteogenic sarcomas from 191
      patients. The level of PGE after a neo-adjuvant therapy of osteogenic sarcoma
      depends upon the individual susceptibility to the drug. Inverse correlation is
      found between the PGE content in the tumor and the degree of therapeutic
      pathomorphosis when adriamycin and methotrexate are used before the operation.
      Single transfusion of the allogenic bone-marrow suspension results in a
      considerable decrease of the PGE level in the osteogenic sarcoma. Possible
      mechanisms of action of different therapeutical methods on the PGE level as well
      as use of the drugs influencing arachidonic acid metabolism in the tumor are
      discussed.

PMID- 8579492
TI  - [Feasibility of cytologic diagnosis of bone tumors].
AB  - Main advantages of the cytological method are demonstrated: possibilities of
      obtaining material from areas which are hardly accessible for open biopsy,
      investigation of bone tumor before or during the operation, etc. Detailed
      biological characteristics of tumor cells by means of DNA-flow cytometry,
      roentgenological and clinical data help to establish correctly a morphological
      variant of bone tumor and thus to choose an adequate therapeutical method.

PMID- 8579493
TI  - [Stimulation of differentiation of LIM 1215 large intestinal tumor cells during
      expression of the p53 exogenous antioncogene or the activated ras oncogene].
AB  - The ability of exogenous p53 tumor-suppressor and activated N-PAS oncogene to
      influence differentiation state of human colon carcinoma LIM 1215 cells and their
      derivatives with acquired resistance to actinomycin D or methotrexate was
      analysed Introduction of retroviral construct expressing human wild-type (wt) p53
      into LIM 1215 cells induced electron microscopic manifestations of enterocytic
      differentiation, i.e. caused an increase in the numbers of cells with microvilli,
      desmosomes and glandular-like lumens. Mutations at codons 248 or 273, the most
      frequent p53 changes in primary colorectal cancer, partially abrogated the
      ability of p53 to stimulate differentiation of LIM 1215 cells. Human M-PASasp12
      showed stronger stimulation of cell differentiation as compared to p53wt.
      Especially high proportion (> 80%) of cells possessing pronounced manifestations
      of columnar enterocytic differentiation was observed after introduction of PAS
      expressing construct into methotrexate-resistant LIM 1215 cell subline that
      originally demonstrated higher maturation than parental cell line. In cell
      subline with two introduced genes, activated PAS and mutant p53His273, the number
      of differentiated cells was similar to that observed in cell culture containing
      only PAS-construct. However, these two sublines differed in the quantity of
      desmosomes as well as in carcino-embryonic antigen (CEA) expression. Comparison
      of expression of different electron microscopic features of cell differentiation
      and CEA expression in cell sublines selected for methotrexate-resistance and/or
      expressing exogenous constructs allows to suppose that p53 tumor-suppressor, PAS
      oncogene and dhfr gene amplification may lead to somewhat distinct
      differentiation states.

PMID- 8579494
TI  - [Oncogene neu in spontaneous and induced rat schwannomas: a study using
      polymerase chain reaction].
AB  - Ethylnitrosourea (ENU) given transplacentally to rats induces schwannomas of the
      cranial, spinal and peripheral nerves with a high frequency of mutation in the
      neu proto-oncogene. To establish the requirement for such mutation in
      tumorigenesis of Schwann cells, spontaneous schwannomas from BD-VI strain rats
      were evaluated for transforming mutations in the transmembrane domain of the
      encoded protein for the neu proto-oncogene. Whereas all five schwannomas induced
      by ENU showed T/A transversions in codon 2012 of neu oncogene upon analysis by
      selective oligonucleotide hybridization and dideoxy sequencing of polymerize
      chain reaction amplified products from paraffin sections, only one of nine
      spontaneous schwannomas from untreated rats exhibited the same mutation.
      Examination of tumours for mutation in codon 12 of Ki-ras proto-oncogene revealed
      normal alleles. Our conclusions based on these data are that the high frequency
      of mutations in neu in ENU-induced tumours appears to be attributable to the
      carcinogen or to the period of development at which exposure occurred, and that
      transforming mutations of the transmembrane domain of neu, are not required for
      tumorigenesis of the Schwann cell.

PMID- 8579495
TI  - [Morphologic diagnosis of insulinoma].
AB  - Insulinoma diagnosis may be sometimes very difficult. Insulinomas and extra-tumor
      pancreatic tissue from 31 patients underwent combined macro- and microscopical
      investigation in order to find morphological changes important for the diagnosis.
      The silver impregnation of pancreatic islands according to Grimelius appeared to
      be most informative. Negative reaction in Langerhans islands shows the presence
      of insulinoma; positive Grimelius reaction makes the diagnosis of insulinoma
      doubtful.

PMID- 8579496
TI  - [Adenocarcinoma of the cervix uteri (immunohistochemistry, ultrastructure,
      differential diagnosis from adenocarcinoma of the adjacent organs].
AB  - Uterine endocervix adenocarcinoma (UEA) is shown to have a structure typical for
      glandular carcinomas. It differs from endometrial carcinoma by cytokeratin (CK) N
      17 expression, that of carcinoembryonic antigen and negative reaction to
      vimentin. CK N 17 found in UEA is not observed in colon and ovarian
      adenocarcinoma. The latter gives a positive response to vimentin. These results
      allow differential diagnosis of endocervix adenocarcinoma and those of colon and
      ovary.

PMID- 8579497
TI  - [Papillary epithelial tumors of the pancreas].
AB  - 4 cases of papillary epithelial tumors (PET) of the pancreas which were initially
      diagnosed erroneously are described in females aged 12, 14, 14 and 41 years. PET
      are circumscribed tumors up to 10 cm in diameter containing numerous cysts. Cyto-
      and histologically they are papillary-solid tumors with hyalinosis, myxomatosis,
      hemorrhage and necrosis. Zymogen type granules, ring-membranous inclusions were
      found electron microscopically. Some cells have a structure of oncocytes.
      Differential diagnostic features of PET are specified.

PMID- 8579498
TI  - [Apudoma of the prostate].
AB  - Prostatic apudomas are represented by well-, moderately- and poorly
      differentiated variants. Histologic differentiation determines various functional
      properties of tumor cells. Tumor cells of well-differentiated apudomas produce
      serotonin, less frequently calcitonin, poorly differentiated ones produce only
      ACTH. Apud cells of moderately differentiated tumors, besides their main function
      to synthesize biogenic amines and hormones (serotonin, ACTH) possess
      immunoreactivity to epithelial membrane antigen, carcinoembryonal antigen and
      prostatic specific antigen.

PMID- 8579499
TI  - [Essay on the history of the Pathology service in the Soviet Army].

PMID- 8579500
TI  - [Bronchiolo-alveolar carcinoma of the lung].
AB  - 283 cases of bronchiolo-alveolar lung carcinoma (BALC) are studied and clinico
      roentgenologic forms are compared with morphological variants. Structural
      features of BALC with and without mucus production as well as those of the
      undifferentiated variants are described.

PMID- 8579501
TI  - [Pathomorphology of kidney lesions induced by non-steroidal anti-inflammatory
      drugs].
AB  - Pathomorphological findings on nephrobiopsies from two groups of patients with
      NSAID-induced kidney lesions are provided. In the first group (9 patients) the
      disease developed in patients of different age after short-term use of NSAID and
      was clinically manifested by acute renal failure with extrarenal allergic
      symptoms (skin, rash, eosinophilia). Morphological features were acute tubulo
      interstitial nephritis without glomerular lesions. In the second group (23
      patients) the disease developed after longterm use of NSAID in older patients
      with a compromised renal blood circulation presenting clinically with nephrotic
      syndrome, and morphologically by acute tubulo-interstitial nephritis with minimal
      change (lipoid nephrosis).

PMID- 8579502
TI  - [Analysis of stomach cancer according to data of the autopsy room at the I.M.
      Sechenov Moscow Medical Academy from 1941-1994].
AB  - Analysis of the above material showed the association of the unfavorable clinico
      morphological indices and poor prognosis with the periods of a socioeconomic
      instability, and the participation of a pathological hormonal background in the
      development of some variants of undifferentiated carcinoma of the stomach.

PMID- 8579504
TI  - [A case of osteosarcoma in a white polar bear].
AB  - A male polar bear was caught at the Franz Josef Land at the age of 1 year and
      then lived in Moscow ZOO for 6 years. Thickening of the distal part of the right
      hind limb was noted in 1993. Destructive changes in the region of epymetaphysis
      were observed roentgenologically suggesting osteolytic osteosarcoma. The bear was
      euthanized and, at autopsy, the tumor had 15 cm in diameter and the distal parts
      of fibula and tibia were completely destroyed. Numerous cavities containing blood
      and necrotic areas were observed in the central parts of the tumor. The tumor was
      firm with hemorrhages in the peripheral parts. Multiple confluent metastases were
      found in all lobes of both lungs with no metastases in other organs. No
      radioactivity was found in the tumor tissue and bone at radiochemical analysis.

PMID- 8579503
TI  - [A rare breast tumor of pluripotential cells].
AB  - A rare relapsing mammary tumor is described. The tumor consisted of a major
      mesenchymal component and a minor tubular one, there were many mitoses.
      Myofibrils, intercellular desmosomal contacts, basal membranes and secretory
      granules were found electron-microscopically. Coexpression of all intermediate
      filament (IF) proteins was found: total keratin, keratins of the liminal and
      myoepithelial types; IF specific for mesenchymal cells - vimentin, that for glial
      cells - glial acidic fibrillar protein and nerve cells - neurofilaments. Thus, as
      distinct from adenomyoepithelioma, the tumor is composed of pluripotential
      elements which are the exception from the rule of the IF proteins tissue
      specificity. The term "pluricelluloma" is suggested for this tumor.

PMID- 8579505
TI  - [An expert system for biopsy diagnosis of lymph node pathology using a personal
      computer].
AB  - The program has been developed for biopsy diagnosis in lymph node disease
      including tumors. The expert knowledge is based on the information about more
      than 200 morphological symptoms of 37 nosological unities: reactive lymphoid
      hyperplasia, metastatic tumors, granulomatous disease and others. The decision
      three consists of three sections: diffuse nontumor processes, inflammatory focal
      processes and tumor diffuse and focal processes. The system can provide a "second
      opinion" for pathologists in their professional activity and may useful as a
      teaching tool for medical students.

PMID- 8579506
TI  - [Computed ergometric test. Critical analysis].

PMID- 8579508
TI  - [Evaluation of chronic morphological changes in the latissimus dorsi, after
      cardiomyoplasty, with magnetic resonance].
AB  - PURPOSE: Long term clinical and hemodynamic benefits of dynamic cardiomyoplasty
      (DC) have been reported. However, no information is available about long-term
      morphological changes in the wrapped latissimus dorsi (LD) muscle in humans.
      METHODS: The latissimus dorsi muscle flap was evaluated by magnetic resonance
      imaging (MRI) in 5 patients submitted to DC for treatment of severe dilated
      cardiomyopathy. All patients were studied from 24 to 52 months after the surgical
      procedure at the time of the cardiomyostimulator replacement. In the interim, LD
      was stimulated with burst of 6 pulses (burst duration 185 msec, burst freq 30Hz)
      synchronized to every cardiac contraction with a maximum of 100 LD
      contractions/min. Images were acquired on a GE Sigma 1.5 T system (TE = 25ms, TR
      = R- Rx2, slice thickness 8mm). RESULTS: The thickness of was 7.6 +/- 0.8mm. In
      addition, the signal intensity of the LD was compared with that of thoracic
      skeletal muscle and was found to be increased (2.19 +/- 0.42). The signal
      intensity was similar to that of subcutaneous fat in those images. CONCLUSION:
      Morphologic changes in the wrapped LD muscle consistent with fatty degeneration
      occur after DC and can be detected by MRI. Further studies will be necessary to
      demonstrate the clinical significance of such LD muscle flap changes.

PMID- 8579507
TI  - [Coronary angioplasty in patients with restenosis. Characterization of clinical
      and angiographic profiles, hospital clinical course, and implications for the
      selection of patients].
AB  - PURPOSE: To define the clinical and angiographic profile of patients undergoing
      to a 2nd or a 3rd coronary angioplaty (PTCA) for the treatment of restenosis, and
      assess the safety and efficacy of redilatation. METHODS: Patients submitted to
      PTCA for a 1st (1stRE) or a 2nd (2ndRE) restenosis, from Jan/1980 through
      Dec/1993, were retrospectively identified, and compared to those undergoing to
      PTCA for de novo lesions (DN). RESULTS: A total of 5,736 underwent to dilatation
      of primary lesions, 610 of a 1stRE, and 64 of a 2ndRE. Patients with restenotic
      lesions had a higher prevalence of diabetes, smoking, history of prior infarction
      (1stRE e 2ndRE) and hyperlipidemia (2ndRE) as compared with primary lesions (p <
      0.05). Besides patients with a 2ndRE had a higher incidence of left ventricular
      dysfunction, as compared to those with DN or a 1stRE (31.3% with EF < 45% in
      group 2ndRE, vs 19.8% and 23.1% in groups 1stRE and DN, respectively, p < 0.05).
      Primary success, infarct rate and mortality were similar in all groups, but
      emergency bypass surgery was significantly higher in the DN (2.1% vs 0.8% in
      1stRE and 0% in 2ndRE, p < 0.05). CONCLUSION: Restenosis can be effectively
      treated by redilatation. Patients with clinical and angiographic features
      predisposing to further recurrence can be better treated with other interventions
      (i.e., coronary stents, bypass surgery).

PMID- 8579509
TI  - [Preferential projections for mapping and ablation of tachycardia of the right
      ventricle outflow. Anatomoradiological study].
AB  - PURPOSE: To select ideal radiologic projections for mapping and ablation of
      tachycardias of right ventricular outflow tract (RVOT). METHODS: Ten hearts from
      human corpses were studied utilizing radiopaque material to identify the
      pulmonary valve and three distinct sites on this valve: septal anterior (A),
      septal posterior (P) and free-wall (L). Next, the hearts were filmed in the
      frontal plane and in oblique projections with 15 degrees increments to the right
      and to the left. The projections in which the sites were lateralized on the
      valve, eased radiologic interpretation and were considered ideal for mapping and
      ablation. Depending on the proximity of the sites to the lateral extremes of the
      pulmonary valve, the projections were considered ideal ( ), intermediary (++) and
      inadequate (+). RESULTS: Projections [table: see text] CONCLUSION: The A site of
      RVOT was best indicated in the 60 and 45 degrees left anterior oblique
      projections; the 0 degree postero anterior projection was best for mapping the P
      site; the L region was best explored in the 60 degrees right anterior oblique
      projection.

PMID- 8579510
TI  - [Effect of dopamine in dopaminergic doses on pulmonary circulation of dogs in
      normoxia and hypoxia].
AB  - PURPOSE: To study if dopamine in dopaminergic doses (1.5 and 4.0
      micrograms/kg/min) had some effect on the pulmonary vasoconstriction mechanism,
      and if in those doses the drug had some action on systemic and pulmonary
      hemodynamic variables, as well as in the pulmonary gas exchange. METHODS:
      Seventeen normal mongrel dogs, anesthetized and paralized under mechanical
      ventilation were submitted to two different gas mixtures: room air (F1O2 = 0.2093
      -10 dogs) and hypoxic mixture (F1O2 = 0.125 -7 dogs). Dopamine was infused in
      both groups during 15 min in the two doses 1.5 and 4.0 micrograms/km/min,
      separated by a period of 30 min. RESULTS: Pulmonary hemodynamics and gas exchange
      variables after infusion of dopamine at 1.5 and 4.0 micrograms/km/min in dogs in
      normoxia and hypoxia. [table: see text] CONCLUSION: Dopamine in the used doses
      had no action on the pulmonary circulation and on the hypoxic pulmonary
      vasoconstriction mechanism; pulmonary gas exchange was not affected by dopamine
      in both doses during normoxia and hypoxia; in the experimental model there was no
      evidence of dopaminergic receptors in the pulmonary vessels.

PMID- 8579511
TI  - [Pregnancy after heart transplantation].
AB  - A 25-year old female patient, with peripartum cardiomyopathy was submitted to
      heart transplantation and became pregnant two years after. Pregnancy was
      uneventful and a baby-girl was born completely healthy. Six years after
      pregnancy, the mother remains well with preserved ventricular function and the
      girl has had a normal development. Although considered a high-risk situation and
      not indicated, pregnancy after heart transplantation is possible, without any
      apparent deterioration of the transplanted graft and with healthy babies being
      delivered.

PMID- 8579512
TI  - [Modified Fontan's operation].
AB  - Nine-year-old female patient presented with cianosis since she was born, fatique
      and dyspnea when sucking. The diagnosis was univentricular heart with left
      ventricular morphology, transposition of the great arteries, moderate pulmonary
      valve stenosis and atrial septal defect. Submitted to surgical correction with
      superior vena cava-right pulmonary artery anastomosis, inferior vena cava
      anastomosis using lateral tunnel, with cardiopulmonary bypass. After surgical
      correction, the clinical and laboratorial (echocardiogram and cardiac
      catheterization) evaluation showed Fontan operation with good surgical results.
      Total cavopulmonary connection was proposed as a modification of the Fontan
      procedure that might have greater benefits than previous proposed techniques. The
      results demonstrate that this modification provides excellent early definitive
      treatment, increasing hemodynamic profile, with low morbidity and mortality, for
      a variety of complex congenital heart lesions.

PMID- 8579513
TI  - [Cardiovascular disease and hormone replacement therapy].

PMID- 8579514
TI  - [Value of the use of milrinone in the treatment of acute crisis in patients with
      congestive heart failure].
AB  - PURPOSE: To assess the hemodynamic effects of milrinone in a 48h intravenous
      infusion in patients with severe congestive heart failure (CHF) (NYHA class III
      or IV). METHODS: Forty patients with CHF were sequentially evaluated. Right heart
      catheterization was performed in order to measure, before and after
      administration of milrinone, several hemodynamic parameters (cardiac index,
      pulmonary wedge pressure, systemic and pulmonary vascular resistance). RESULTS:
      There was a significant improvement in hemodynamic parameters (cardiac index,
      cardiac output), and a decrease in systemic vascular resistance and pulmonary
      vascular resistance. Serious side effects were not observed in these patients.
      CONCLUSION: These findings indicate that milrinone is effective in the treatment
      of deteriorating phases of CHF and suggest that milrinone should be used in these
      select patients.

PMID- 8579515
TI  - [Clinical and angiographic profile and selection of patients for coronary
      angioplasty of restenosis].

PMID- 8579516
TI  - [Dyslipidemias and endothelial changes].

PMID- 8579518
TI  - [The importance of the dyslipidemia-arterial hypertension link in coronary
      atherosclerosis].

PMID- 8579517
TI  - [Dyslipidemia and blood coagulation].

PMID- 8579519
TI  - [Dyslipidemia in women. Physiopathological and therapeutic aspects].

PMID- 8579520
TI  - [Lipoproteins, antioxidants, and coronary cardiopathy].

PMID- 8579521
TI  - [The value of the treatment of dyslipidemias in the prognosis of patients with
      coronary artery disease].

PMID- 8579522
TI  - [Cholesterolemia reduction and mortality. Critical analysis].

PMID- 8579523
TI  - Hemodialyzer performance: a review of the trends over the past two decades.
AB  - Using data generated in the course of an evaluation program for hemodialyzers and
      associated devices, which was supported by the Medical Devices Agency of the
      Department of Health, we have compared the performance characteristics of 23
      hemodialyzers evaluated 20 years ago with those of 18 hemodialyzers evaluated
      during 1993-1994. Surface areas of the two groups ranged from 0.6-2.5 m2 (mean
      1.13 m2) and 0.6-1.8 m2 (mean 1.18 m2), respectively. The device performance has
      been compared both in vivo (small molecular clearance) and in vitro (middle
      molecular clearance and ultrafiltration coefficient) at blood and dialysate flows
      of 200 and 500 ml/min, respectively. Our comparison shows that over the past 2
      decades there has been a marked improvement in functional performance. For
      clearance of small molecules, current dialyzers using cellulose-based membranes
      offer a 47% improvement for urea clearance, within the surface area range < 1.2
      m2, while for dialyzers whose surface area is > 1.2 m2 the improvement is less
      marked (12%). The improvements noted in the clearance of creatinine were similar.
      Associated with the improved clearance of small molecules was an improved middle
      molecular clearance (74% for surface areas < 1.2 m2 and 63% for surface areas >
      1.2 m2) and an increased ultrafiltration coefficient, higher by 154 and 133%,
      respectively, for the two surface area groups. Due to the smaller number of
      devices in the modified cellulose and synthetic membrane categories, it has not
      been possible to make such a detailed comparison. However, the experimental data
      demonstrate that devices currently produced incorporating modified cellulose and
      synthetic membranes overlap in performance and that in those devices that were in
      clinical use 20 years ago using synthetic membranes, current equivalents have
      also improved. These improvements are reflected in the concomitant reduction of
      treatment times from 30 h/week in 1970 to 12 h or less currently.

PMID- 8579524
TI  - Middle molecules: toxicity and removal by hemodialysis and related strategies.
AB  - Renal failure results in the retention of metabolites which may arbitrarily be
      grouped according to their molecular weight: low (< 300 daltons molecular
      weight), middle (300-15,000 daltons), and high (> 15,000 daltons). Opinion in
      respect to the relative importance of these groups varies. Initially it was
      thought that small molecules were important. In the mid-1970s, investigators
      identified the possible pathophysiological role of middle molecules. However,
      since positive identification of such molecules was difficult, opinion has
      shifted back in favor of small molecules, and little attention, with the
      exception of beta 2 microglobulin, has been paid to middle molecules and their
      removal by hemodialysis and related therapies. In this review current knowledge
      regarding middle molecules identified as uremic toxins and their removal by
      hemodialysis and associated therapies are discussed.

PMID- 8579525
TI  - Hemodialyzer performance: biological indices.
AB  - In the last decade there has been a rapid increase in the number of biological
      indices that could potentially be used as measures of hemodialyzer or membrane
      biocompatibility. Consequently, it has become more challenging for all of those
      involved in renal replacement therapy to evaluate the relative merits of one
      membrane versus another when faced with their ever increasing variety of
      parameters. This review attempts to summarize the current array of biological
      parameters described in the literature as indices of biocompatibility and provide
      a critique of their utility. Emphasis is placed on measures of activation of the
      plasma cascade systems, complement, coagulation, and kinin as primary indices of
      biocompatibility. Additional information on neutrophil, monocyte, platelet,
      lymphocyte and natural killer (NK) cell effects may provide further insight into
      blood-membrane mediated interactions although many of these may parallel plasma
      cascade systems activation. The importance of good statistical design and
      analysis is emphasized to ensure meaningful interpretation of any study.

PMID- 8579526
TI  - Application of a standard method to characterize clearance blood flow
      relationships in hemodialysis.
AB  - The effectiveness of solute removal of a hemodialyzer may be judged by the
      ability of the device to remove solutes over the clinical range of blood flow
      rates. The expression of solute removal characteristics of hemodialyzers at
      standard or specific blood flow rates is important for clinical use and
      comparison. The solute removal at a specific blood flow rate is derived
      mathematically, usually by the fitting of a curve to the blood flow solute
      removal characteristics established experimentally over a range of blood flow
      rates. The commonly used methods of obtaining such a relationship are discussed
      and a new method of curve fitting is described. This method is derived from the
      mathematical theory defining the overall dialyzer mass transport relationship
      which governs the clearance blood flow relationship in any dialyzer. The derived
      relationship between the blood flow rate and the clearance has been validated
      using data generated for a commercially produced hemodialyzer.

PMID- 8579527
TI  - Ultrafiltration and backfiltration during hemodialysis.
AB  - Ultrafiltration is the pressure-driven process by which hemodialysis removes
      excess fluid from renal failure patients. Despite substantial improvements in
      hemodialysis technology, three significant problems related to ultrafiltration
      remain: ultrafiltration volume control, ultrafiltration rate control, and
      backfiltration. Ultrafiltration volume control is complicated by the effects of
      plasma protein adsorption, hematocrit, and coagulation parameters on membrane
      performance. Furthermore, previously developed equations relating the
      ultrafiltration rate and the transmembrane pressure are not applicable to high
      flux dialyzers, high blood flow rates, and erythropoietin therapy. Regulation of
      the ultrafiltration rate to avoid hypotension, cramps and other intradialytic
      complications is complicated by inaccurate estimates of dry weight and patient-to
      patient differences in vascular refilling rates. Continuous monitoring of
      circulating blood volume during hemodialysis may enable a better understanding of
      the role of blood volume in triggering intradialytic symptoms and allow
      determination of optimal ultrafiltration rate profiles for hemodialysis.
      Backfiltration can occur as a direct result of ultrafiltration control and
      results in transport of bacterial products from dialysate to blood. By examining
      these problems from an engineering perspective, the authors hope to clarify what
      can and cannot be prevented by understanding and manipulating the fluid dynamics
      of ultrafiltration.

PMID- 8579528
TI  - Convective mass transfer in hemodialysis.
AB  - Convective mass transfer in hemodialysis is associated with ultrafiltration (UF).
      In the absence of diffusion as in hemofiltration, the convective clearance is
      equal to S.QF where S is the apparent solute sieving coefficient and QF the UF
      flow rate, but the convective contribution significantly decreases when diffusion
      is present. A rigorous calculation of the combined diffusion-convection mass
      transfer for partially rejected solutes is very complex. In this paper we review
      various models of mass fluxes found in the literature. Since all these models
      express the mass flux through the membrane as a linear function of blood and
      dialysate concentrations with different coefficients, we present a general
      expression for the hemodiafiltration clearance combining diffusion and convection
      which can be adapted to each model of mass flux. A surprising result is that the
      convective contribution to the clearance is, in the limit of dominant
      ultrafiltration, independent of the solute sieving coefficient, in contrast to
      the model of Villaroel et al. This is due to the effect of increased solute
      concentration at the membrane which compensates exactly for the effect of the
      sieving coefficient. This effect is overlooked in the Villaroel et al. model
      which assumes well mixed blood and dialysate compartments. Comparison with in
      vitro clearance measurements for urea, creatinin, vitamin B12, and myoglobin
      (16,000 daltons) supports this observation even when diffusion dominates as in
      the case of clinical conditions for hemodiafiltration. An empirical correlation
      for the overall clearance valid for all solutes and blood flows between 200 and
      500 ml/min is found to be K = KD + 0.43 QF + 8.3 x 10(-3) Q2F when clearances and
      QF are in ml/min.

PMID- 8579529
TI  - Influence of the dialyzer membrane material on sodium transport in hemodialysis.
AB  - Traditionally Gibbs-Donnan coefficients based on the mean charge of plasma
      proteins are used as the only correction factor in equations describing sodium
      transport across the dialyzer membrane. This ignores the possible impact of the
      membrane material. Correction coefficients (CC) of the whole dialyzer were
      measured during in vivo dialysis as a quotient of dialysate to plasma sodium in
      an equilibrated state for different membrane materials used in commercially
      available dialyzers. Their mean value and correlation with total plasma protein
      content (TPP) were evaluated. CC for the six materials evaluated differed both in
      the intercept and slope of the regression line CC versus TPP: Cuprophan 1: CC =
      1.0253 - 0.00017 x TPP; Hemophan 1: CC = 1.119 - 0.00175 x TPP; Hemophan 2: CC =
      1.095 - 0.00111 x TPP; PMMA: CC = 1.0353 - 0.00044 x TPP; SCE:CC = 1.114 -
      0.00145 x TPP; and Cuprophan 1:CC = 1.0562 - 0.00065 x TPP. The observed
      differences are attributed to the different charge densities of the membrane
      materials and suggest that for a precise description of sodium transport, the
      role of the membrane material needs to be considered.

PMID- 8579530
TI  - The influence of the dialysate flow rate on hollow fiber hemodialyzer
      performance.
AB  - The clearance characteristics of two sizes of hemodialyzers (0.9 m2 and 1.5 m2)
      from the same range of products have been studied over the dialysate flow range
      of 500-3,000 ml/min to establish the device's overall mass transfer resistance
      characteristics. The results obtained demonstrate a difference in the overall
      mass transfer resistance which is most marked at the commonly used dialysate flow
      rate of 500 ml/min. This difference suggests that the increase in size results in
      the introduction of flow imperfections which reduces the benefit that might be
      gained by the use of a larger surface area. Results established indicate a
      reduction in the overall mass transfer resistance with an increasing dialysate
      flow rate. This reduction is attributed to the presence of turbulence in the
      dialysate pathway at higher flow rates. The presence of such turbulence was
      confirmed by visual inspection of the dialyzer after the completion of the study
      when it was noted that the original well-ordered configuration present in a new
      dialyzer had been substantially disturbed. Correlation of the dialysate flow rate
      with overall mass transfer resistance by the use of a Wilson plots indicates a
      nonlinear relationship. This nonlinearity is attributed to a nonfully developed
      turbulent flow profile in the dialysate pathway.

PMID- 8579531
TI  - Long-term follow-up of 6-8 mm brachioaxillary polytetrafluorethylene grafts for
      hemodialysis.
AB  - Eight millimeter expanded polytetrafluoroethylene (e-PTFE) grafts, tapered to 6
      mm at the arterial site, are used by our group in the upper arm in order to avoid
      midgraft stenosis observed with other graft sizes. Long-term results (1-12 years)
      on 157 6-8 mm brachioaxillary e-PTFE grafts (Gore-Tex) are analyzed. Early
      failure was found in 4 grafts (2.5%). The rate of late complications was 0.37
      episodes per graft-year. Steal syndrome, found in 4 cases (2.5%), was
      successfully treated in 3 cases by graft banding. Neither midgraft nor arterial
      anastomotic stenosis was observed in the 63 grafts requiring surgical
      thrombectomy or fistulography. The primary patency rates were 73%, 53%, and 41%
      at 1, 3, and 5 years, respectively. The secondary patency rates were 91%, 80%,
      and 72% at 1, 3, and 5 years, respectively. Comparison between both curves by the
      log rank test was significant (p < 0.001) expressing the efficiency of rescue
      surgery. We conclude that a 6-8 mm graft can be successfully used for dialysis in
      the brachioaxillary position.

PMID- 8579532
TI  - Growth regulation of endothelial cells by tissue fragments: analysis on mechanism
      of rapid endothelialization of tissue-seeded vascular prosthesis in a three
      dimensional culture system.
AB  - Rapid endothelialization of the inner surface was reported in an autologous
      tissue-seeded vascular prosthesis. We applied a three-dimensional in vitro
      culture system to elucidate the precise mechanism of rapid endothelial coverage
      of a tissue-seeded vascular prosthesis. Human venous, omental, adipose and
      striated muscle tissue fragments were harvested from surgical specimens. They
      were embedded in collagen gel, and 2.0 x 10(5) bovine aortic endothelial cells
      (BAECs) were seeded on the gel. The number of BAECs was counted on Days 2 and 7.
      Growth rate of BAECs was facilitated on the collagen gel with omental and
      striated muscle tissue fragments (p < 0.05). Factor VIII-negative spindle cells
      migrated around tissue fragments, especially around the omental and striated
      muscle tissue fragments. Rapid endothelialization of a tissue-seeded vascular
      prosthesis may result from facilitation of EC proliferation by viable tissue
      fragments and migrated cells. These results confirm tissue fragments regulate EC
      growth, and are useful as bioengineering tools.

PMID- 8579533
TI  - Polyvinylidene fluoride monofilament sutures: can they be used safely for long
      term anastomoses in the thoracic aorta?
AB  - Polyvinylidene fluoride (PVDF) represents an attractive alternative to
      polypropylene as a monofilament vascular suture because of its satisfactory
      physicochemical properties, it ease of handling, and its good biocompatibility.
      However, the polymer's ability to remain mechanically and chemically stable when
      exposed to a mild hydrolytic environment over the long term has yet to be
      demonstrated. One in vitro study involved the comparison of the long-term
      relative resistance of PVDF and polypropylene sutures to hydrolysis for a period
      of 9 years. The PVDF suture showed major molecular rearrangements from the
      original ratio of three crystalline structures to the single beta crystalline
      phase. The observation of some surface oxidation and water inhibition did not
      significantly modify the tensile strength of the PVDF suture, which retained
      92.5% of its original value. In contrast, the polypropylene sample did not
      undergo any recrystallization but was associated with more oxidation byproducts
      and more water molecules near the surface, which contributed to a 46.6% loss in
      initial tensile strength. An in vivo study confirmed that PVDF sutures are
      biocompatible and are able to maintain satisfactory biostability when used to
      anastomose thoracic aortic allografts for a period of 6 months in the dog. The
      cellular reaction of fresh allografts as well as the control autografts to PVDF
      sutures was minimal. In other allografts that had been preserved in a
      supplemented medium for 1 week prior to implantation, the PVDF sutures healed
      satisfactorily with the formation of neocollagen and few macrophages surrounding
      the monofilament. No evidence of instability at the allograft-host artery
      junction was observed, confirming that the PVDF sutures were able to ensure a
      secure anastomosis in the thoracic aorta. PVDF sutures have demonstrated superior
      long-term biostability in vitro and minimal tissue response in vivo. These are
      two essential requirements when evaluating the use of a suture for vascular
      surgery in general and thoracic aortic surgery in particular.

PMID- 8579534
TI  - Sharing care between allied health professionals and general practitioners.

PMID- 8579535
TI  - Chronic illness in the adolescent.
AB  - A review of the broad range of problems facing the adolescent with chronic
      illness is undertaken. The issues are illustrated by the case of a young man with
      the McCune-Albright syndrome. This rare disorder has impacted enormously on the
      patient, his family and his doctors.

PMID- 8579536
TI  - Engaging the adolescent patient.
AB  - With their knowledge of local community, families and schools, general
      practitioners are the ideal providers of primary health care to young people;
      however, doctors sometimes find it difficult to communicate with adolescents.
      Adolescents are often anxious and reluctant to visit a doctor. This article
      outlines possible approaches to the adolescent in the medical consultation that
      may help start the therapeutic relationship in a positive manner.

PMID- 8579537
TI  - Primary care assessment of a patient with an eating disorder.
AB  - Eating disorders have become commoner in young Australian women over the past two
      decades, making their presentation in general practice more likely. Eating
      disorders vary considerably in severity from brief single episodes to severe
      disorders with prominent weight loss or maladaptive behaviours. Assessment should
      therefore focus on estimating the severity of the disorder to indicate the most
      appropriate treatment approaches.

PMID- 8579538
TI  - Compliance issues in adolescence: practical strategies.
AB  - Understanding the process of adolescent development is crucial to engendering
      good compliance. Successful outcomes can be achieved by approaching adolescents
      with respect and negotiating with them shared treatment goals. A few simple
      interventions can help make the issue of compliance in adolescents less
      problematic.

PMID- 8579539
TI  - Adolescent suicide attempts: a general practice perspective.
AB  - General practitioners have a vital role in recognising, assessing and managing
      the suicidal adolescent. The GP's knowledge of the local community and services
      allows them to intervene effectively to prevent future suicidal behaviour. This
      may also involve the care and follow-up of survivors of youth suicide.

PMID- 8579540
TI  - Healthy masculinity starts in boyhood.
AB  - Addressing the crisis in men's health is more subtle than lecturing on lifestyle,
      diet or safety. Men's risk-taking behaviour is driven by deep unhappiness with
      life. Many of the mental health problems of men may be due to the estrangement
      between fathers and sons since the industrial revolution and the lack of self
      worth this has created. Practical steps such as men's group are being fostered by
      GPs and others around Australia.

PMID- 8579541
TI  - Slipped upper femoral epiphysis. A diagnosis to consider.
AB  - It is important to diagnose this condition as early as possible to enable prompt,
      operative treatment and prevent further slippage. The initial presentation may
      seem benign and a high index of suspicion is needed. This article reviews the
      epidemiology, clinical presentation, diagnosis, complications and subsequent
      management of this condition.

PMID- 8579542
TI  - Injury and general practice in Australia.
AB  - OBJECTIVE: To describe the extent to which general practices are involved in the
      initial management of injury in Australia. METHODS: Data were derived from a
      secondary analysis of the 1989-1990 National Health Survey (NHS); a population
      based multi-stage and list sample survey of the Australian population. The study
      variables used in this analysis included age, sex, country of birth, employment
      status, place of most recent accident, number of reduced activity days subsequent
      to injury and where presenting for treatment of the injury. RESULTS: The ratio of
      general practice to hospital emergency department attendance for treatment of
      injury was 1.5:1 (95% confidence limits = 1-2:1). The two groups of patients
      differed by age, employment status, place of most recent accident but not by sex
      or country of birth. CONCLUSION: Results from hospital studies should not be
      extrapolated to produce community estimates of injury incidence in Australia.
      General practice should be specifically included in future injury research and
      control projects.

PMID- 8579543
TI  - Management of low HDL cholesterol.
AB  - A low concentration of high density lipoprotein (HDL) cholesterol is a powerful
      predictor of premature coronary heart disease (CHD). This paper presents an
      overview of the function of HDLs and their relationship with CHD. It summarises
      conditions in which HDL cholesterol levels are low and discusses the evidence
      that increasing HDL cholesterol levels may be beneficial. It outlines measures
      which raise the level of HDL cholesterol and concludes with some practical
      suggestions for the management of low HDL states.

PMID- 8579544
TI  - Common skin, hair and nail problems during the first six months.

PMID- 8579545
TI  - Roger Peter Strasser. Pioneer professor of rural practice.

PMID- 8579546
TI  - Acute otitis media.

PMID- 8579547
TI  - Practice tip. Suprapubic aspiration of urine.

PMID- 8579549
TI  - Musculoskeletal medicine tip. Tietze's syndrome.

PMID- 8579548
TI  - An infection from a penetrating plant wound.

PMID- 8579550
TI  - Management of severe trauma. Part 1: Airway and breathing.

PMID- 8579551
TI  - Death in the desert.

PMID- 8579552
TI  - Death in the desert.

PMID- 8579553
TI  - Is rural practice a distinct discipline?

PMID- 8579554
TI  - Abuse of temazepam capsules.

PMID- 8579555
TI  - GP autopsies.

PMID- 8579556
TI  - Training program mismatch.

PMID- 8579557
TI  - Cranial cruciate ligament rupture in the dog--a retrospective study comparing
      surgical techniques.
AB  - Three surgical techniques, grouped as intra-articular techniques, extracapsular
      techniques and fibular head transposition, were used for repair of the cranial
      cruciate ligament (CCL)-deficient stifle in 113 dogs over a 4 year 4 month
      period. The clinical outcome of the techniques were compared using information
      provided by the owners and physical examination. Regardless of surgical
      technique, 85.7 to 91.0% of dogs showed clinical improvement after surgery.
      However, less than 50% of dogs became clinically sound on the operated leg and
      9.0 to 14.3% of dogs remained persistently lame on the operated leg. No
      statistical association was found between result after surgery and age, body
      weight, sex, duration of injury before surgery, association with injury, tibial
      plateau angle, degree of radiographic osteoarthritis before surgery or the
      presence of concurrent medial meniscal injury. On physical examination, extra
      capsular techniques appeared superior to the fibular head transposition in terms
      of joint stability and limb function. Concurrent medial meniscal injury
      necessitating meniscectomy existed in 48.0% of cases. Twenty-two percent of dogs
      ruptured their contralateral CCL at an average of 14 months after the first.

PMID- 8579558
TI  - The persistence of foot-and-mouth disease virus on wool.
AB  - Five Suffolk sheep, held in a high-security isolation room, were exposed for 2
      hours to the aerosol of 3 mature pigs that had been infected with foot-and-mouth
      disease virus (FMDV), strain O1-BFS. The fleeces of 3 of the sheep were
      contaminated with FMDV at 2 days post exposure (dpe), while at 5 dpe the fleeces
      of all 5 sheep were more extensively, and more heavily, contaminated. The
      persistence of FMDV on contaminated wool was examined in vitro using multiple 0.5
      g samples of Merino wool that were each contaminated with one of 3 strains of
      FMDV in tissue-cultured medium: O1-BFS, O-Morocco (O-MOR 9/91) or an Asia 1
      strain (TAI 1/90). Wool samples were held at either 4 degrees C, 18 degrees C or
      37 degrees C, and decay curves were established for each virus at each
      temperature. These curves predicted that O1-BFS, O-MOR 9/91 and TAI 1/90 would
      fall below detectable levels at 72, 70 and 48 days post contamination (pc),
      respectively, for wool stored at 4 degrees C; at 11, 12 and 12 days pc,
      respectively, for wool stored at 18 degrees C; and at 57, 68 and 33 hours pc,
      respectively, for wool stored at 37 degrees C. For wool contaminated with O1-BFS
      infected sheep faeces, urine or blood, or with O1-BFS-infected cattle saliva,
      decay curves predicted virus to persist for 5 to 11 days pc at 18 degrees
      C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579559
TI  - Direct effects of induced parturition on subsequent reproductive performance of
      dairy cows from commercial herds in south-western Victoria.
AB  - Reproductive performance was compared between cows whose previous parturition was
      induced and non-induced cows with similar calving dates, in 49 winter-calving,
      pasture-fed, commercial dairy herds in south-western Victoria. Parturition was
      induced in winter when most cows were between 27 and 35 weeks of pregnancy.
      Reproductive performance was assessed during the next mating period after
      induction which was mainly in spring of the same year. Percentages of cows in
      induced and untreated groups that were not pregnant after the mating period (9.0%
      and 7.2%, respectively) did not differ significantly. Induction tended to
      increase the percentage of cows of unknown pregnancy status. Mean percentages for
      induced and untreated groups were 11.5% and 7.9%, respectively. Induced and
      untreated groups calved at similar intervals after the planned start of calving
      in the following year, and the percentages of groups that required induction in
      that year did not differ significantly. The direct effects of induced parturition
      on reproduction were therefore concluded to be minimal. In seasonal calving
      herds, improvements in reproductive performance could be expected among cows
      whose calving dates were altered substantially by induction, due to increased
      intervals from calving to mating start date.

PMID- 8579560
TI  - Studies on failure of T strain live Babesia bovis vaccine.
AB  - Field investigations of the protection afforded by the Australian live Babesia
      bovis vaccine used in the early 1990s (T strain) revealed inadequate vaccine
      induced protection in certain herds. Vaccination/challenge trials using 207
      experimental cattle were conducted to evaluate the protection afforded by T
      strain B bovis against field isolates from these herds. The trials investigated
      whether isolates that could 'break-through' T strain immunity were present in the
      field, the ability or inability of specific cattle to develop protective immunity
      after vaccination with T strain and the effect of attenuation and maintenance
      procedures on the immunogenicity of T strain. The results showed that B bovis
      parasites present early in the process of attenuation of T strain were more
      protective than those remaining late in the process. They also showed that cattle
      from properties experiencing vaccine failures were less protected by T strain
      vaccination than Bos taurus cattle randomly selected from the general population
      if vaccinated with highly attenuated T strain. A hypothesis is offered to explain
      these findings.

PMID- 8579561
TI  - Maintenance of acquired immunity to Trichostrongylus colubriformis in Merino
      sheep that are losing weight.
AB  - The effect of loss of weight on maintenance of acquired immunity to
      Trichostrongylus colubriformis in Merino sheep was assessed in 2 experiments.
      Adult Merino sheep with previously acquired immunity to T colubriformis were
      housed in individual pens. Sheep were infected 3 times weekly with 2000 T
      colubriformis larvae. A diet based on chopped oaten and lucerne hay (experiment
      1) or a pelleted diet based on lucerne hay and grain products (experiment 2), was
      offered in amounts to sustain a moderate gain in body weight, or was reduced step
      wise to cause a loss in body weight. Worm egg counts were determined weekly. The
      reduction in feed on offer resulted in a mean weight loss of 4.0 kg over 9 weeks
      (experiment 1) or 4.8 kg over 7 weeks (experiment 2). Based on worm egg counts,
      there was no indication of a change in immunity to T colubriformis in either of
      the experiments. These results suggest that acquired immunity to T colubriformis
      in adult sheep that are exposed to infection is maintained during periods of
      moderate loss of weight associated with inadequate nutrition.

PMID- 8579562
TI  - Phenylbutazone in racing greyhounds: plasma and urinary residues 24 and 48 hours
      after a single intravenous administration.
AB  - The concentrations of phenylbutazone (PBZ), oxyphenbutazone (OPBZ) and
      gammahydroxyphenylbutazone (OHPBZ) in plasma and urine from 50 Greyhounds 24 and
      48 h after the intravenous administration of a single dose of PBZ (30 mg/kg) were
      measured. The 24 h plasma concentrations of OPBZ and OHPBZ, the 48 h plasma
      concentration of OHPBZ and the 24 h urinary concentration of PBZ were normally
      distributed, while log transformations were required before the 24 h plasma
      concentration of PBZ and the 24 and 48 h urinary concentrations of OPBZ and OHPBZ
      became normally distributed. The 95%, 99%, 99.9% and 99.99% upper predicted
      confidence intervals for both 24 h and 48 h plasma and urinary concentrations
      demonstrated wide potential variation in the concentration of the analytes should
      PBZ be administered to Greyhounds. The 24 h plasma and urinary concentrations of
      PBZ were weakly correlated, but no similar relationship existed for OPBZ or
      OHPBZ. The urinary concentrations of each analyte were not affected by the
      trainer or sex of the Greyhound or the urinary pH. We conclude that it would be
      impossible to predict the timing of the PBZ administration or the plasma
      concentration of PBZ from the measurement of the concentration of PBZ in a single
      sample of urine.

PMID- 8579563
TI  - Evidence of molecular heterogeneity for generalised glycogenosis between and
      within breeds of cattle.
AB  - Northern analyses revealed normal levels of acidic alpha-glucosidase mRNA in
      cultured fibroblasts from a Shorthorn calf affected with glycogenosis but a gross
      deficiency in an affected Brahman calf. Analyses of acidic alpha-glucosidase
      activity, relative to that of other lysosomal enzymes, in blood mononuclear cells
      revealed greater variation within and between Brahman herds than Shorthorn herds.
      A Msp1 restriction fragment length polymorphism associated with glycogenosis in
      Brahmans was not found in Shorthorns. These results are considered in relation to
      molecular heterogeneity for AAG deficiency in cattle and its implications for
      disease control programs.

PMID- 8579564
TI  - Long-term survival of four dogs with disseminated Aspergillus terreus infection
      treated with itraconazole.
AB  - Four dogs with disseminated aspergillosis caused by Aspergillus terreus were
      treated with oral itraconazole for 190 to 1095 days. Infection was eliminated in
      1 dog. Two dogs were treated for 1000 and 1095 days but were eventually
      euthanased 572 and 485 days after treatment was stopped. At necropsy both dogs
      had widespread aspergillosis. The fourth dog was euthanased for other reasons
      after 190 days of treatment when it was showing a good clinical response although
      there was radiographic evidence that the disease was progressing.

PMID- 8579565
TI  - Hyperkalaemic periodic paralysis in Australian quarter horses.
AB  - Three Quarter Horse stallions and 5 of their 11 tested progeny were diagnosed as
      affected with the inherited autosomal dominant defect hyperkalaemic periodic
      paralysis in Victoria in 1992. The diagnoses were based on the appearance of
      clinical signs and associated increased plasma potassium concentrations in
      response to oral potassium loading. All affected horses were descendants of the
      American Quarter Horse Impressive. Indirect evidence indicates that at least 3
      other affected Quarter Horse stallions have stood or are standing at stud in
      Australia. The clinical details of the affected horses are described and the size
      of the affected population in Australia is discussed.

PMID- 8579566
TI  - Klossiella equi infection in horses; sporocyst stage identified in urine.

PMID- 8579567
TI  - Tissue expression of endothelin-1 mRNA in endotoxaemia.
AB  - Circulating endothelin-1 concentrations are elevated in animal models of sepsis.
      The major actions of endothelin-1 appear to be as a local autocrine and paracrine
      factor, rather than as a circulating hormone, and plasma concentrations may not
      reflect local tissue concentrations. We therefore measured tissue expression of
      mRNA encoding pre-pro-endothelin-1 by RNase protection assays, as an indicator of
      local production of ET-1 in an in vivo rat model of endotoxaemia. The effects of
      dexamethasone pre-treatment were also examined. There was a tissue-specific
      increase in pre-pro-endothelin-1 mRNA in endotoxaemia, apparent at 6h after
      endotoxin challenge in heart and lung. No significant changes in expression were
      seen in kidney or skeletal muscle. Dexamethasone pre-treatment significantly
      attenuated the rise in pre-pro-endothelin-1 mRNA in heart at 6h. Therefore, we
      have demonstrated tissue-specific differences in the effect of endotoxin upon pre
      pro-endothelin-1 mRNA expression and in sensitivity to dexamethasone. This could
      account for some of the inter-tissue differences seen in local vascular response
      to endotoxin.

PMID- 8579568
TI  - Characterization of zeta-crystallin inhibition by juglone.
AB  - Guinea pig lens zeta-crystallin showed hyperbolic saturation curves with 9,10
      phenanthrenequinone (PAQ). 5-hydroxy-1,4-naphthoquinone (juglone) and NADPH.
      Whereas camel lens zeta-crystallin showed hyperbolic saturation curves only with
      PAQ and NADPH, but slightly segmoidal with juglone. For both enzymes PAQ was the
      preferred substrate. The catalytic center activity (Kcat) values indicated that
      camel zeta-crystallin catalyzed the reduction of PAQ more efficiently than the
      guinea pig lens zeta-crystallin, although the Km values of the two enzymes for
      this quinone were very similar. The guinea pig lens zeta-crystallin catalyzed the
      reduction of Juglone far more efficiently than that of the camel lens zeta
      crystallin. Juglone did not serve as an efficient substrate for both zeta
      crystallins compared to PAQ and appeared to act as a potent competitive
      inhibitor, with Kl values of 75 nM and 20 microM for guinea pig lens zeta
      crystallin and camel lens zeta-crystallin, respectively. Thus, the camel lens
      zeta-crystallin was less active toward juglone as a substrate as well as less
      sensitive to its inhibitory action, when compared with guinea pig lens zeta
      crystallin. The inhibition mechanism of guinea pig and camel lens zeta-crystallin
      by juglone is discussed.

PMID- 8579569
TI  - Human superoxide dismutase cDNA transfection and its in vitro effect on cold
      preservation.
AB  - In order to elucidate the role of superoxide dismutase (SOD on ischemia
      reperfusion injury, bovine and porcine aortic endothelial cells were transfected
      with retroviral vector LSODRNL containing human Cu,Zn-SOD cDNA and their SOD
      activities were evaluated by measuring superoxide scavenging capability.
      Successful augmentation of Cu,Zn-SOD up to 2.7-fold in bovine and 1.9-fold in
      porcine cells was obtained. After 24 h cold preservation followed by 4 h
      rewarming, cell viability compared with that of pre-preservation was
      significantly increased in both types of cells (P < 0.01). Moreover, after
      exposure to superoxide, viability of the porcine cells with high SOD activity was
      significantly improved compared to control cells. We consider that transfection
      of human Cu,Zn-SOD cDNA to arterial endothelial cells is useful for preventing
      from cold preservation-rewarming or ischemia-reperfusion injury.

PMID- 8579570
TI  - Role of apoptosis in growth and differentiation of proximal tubule cells in
      primary cultures.
AB  - In this study, we assessed the profile of cell proliferation, Na,K-ATPase
      activity and apoptosis in primary cultures of proximal tubule cells. Freshly
      isolated proximal tubules exhibited apoptosis very early in culture: floated
      cells within 6 hr; attached tubule cells within 20 hr. The onset of apoptosis in
      either attached or floated proximal tubules was accompanied by a decline of Na,K
      ATPase activity, indicating a close relationship between apoptosis and
      dedifferentiation. The ratio of apoptosis was highest at the lag phase and lowest
      at the rapid growth phase, reflecting an inverse relationship between mitogenesis
      and apoptosis. Our data indicate that apoptosis is involved in the growth and
      early downregulation of Na,K-ATPase activity in primary cultures of proximal
      tubule cells.

PMID- 8579571
TI  - Atrial natriuretic factor (ANF) prohormone accumulates in the IgG fraction of
      anti-ANF hybridoma-bearing mice.
AB  - We demonstrate immunoreactive mouse atrial natriuretic factor (ANF) in the IgG
      fraction prepared from ascites or serum of mice bearing an anti-rat ANFArg101
      Tyr126 hybridoma. The HPLC profile of the ANF demonstrates that the IgG fraction
      contains both mature ANFSer99-Tyr126 and the prohormone ANFAsn1-Tyr126. The
      presence of circulating prohormone in the hybridoma-bearing mice is not secondary
      to changes in fluid volume due to ascites formation. The anti-ANF antibody
      appears to protect the ANFAsnl-Tyr126 from both maturation and rapid receptor
      mediated clearance. Our results suggest, therefore, that the ANFAsn1-Tyr126 can
      be secreted into a compartment that is accessible to antibody and that maturation
      of the ANF prohormone may be an extracellular event.

PMID- 8579572
TI  - The guanylyl cyclase core of an atrial natriuretic peptide receptor: enzymatic
      properties and basis for cooperativity.
AB  - The enzymatic properties of a cloned atrial natriuretic peptide receptor are
      described. The renatured catalytic core had maximal activity with Mn2+, and all
      nucleoside triphosphates inhibited the enzyme competitively. The catalytic
      specificity of the enzyme was tested directly. The cyclase reaction was specific
      for guanine, producing cGMP and cyclic deoxyGMP. Surprisingly, deoxyguanylyl
      cyclase kinetics were classical, unlike the positive cooperativity seen for
      guanylyl cyclase activity, suggesting that the 2' hydroxyl group of GTP is
      necessary for the allosteric mechanism.

PMID- 8579573
TI  - Detection of different quasispecies of hepatitis C virus core region in cancerous
      and noncancerous lesions.
AB  - The quasispecies of hepatitis C virus (HCV) core region in non-cancerous and
      cancerous hepatocellular carcinoma (HCC) lesions, respectively, of 7 patients
      with hepatocellular carcinoma were studied. Multiple fluorescence based
      polymerase chain reaction (PCR)-single strand conformation polymorphism exhibited
      a different set and a larger number of quasispecies in cancerous portions than
      those in non-cancerous portions. DNA sequencing of PCR-amplified core region
      substantiated an accumulation of nucleotide substitutions, and a greater number
      of quasispecies in cancerous portions than those in non-cancerous portions. The
      deduced amino acid sequences disclosed that at the peptide position 45, Ser is
      dominant in non-cancerous lesions, and Gly in cancerous lesions, respectively.
      Thus, HCV in hepatocellular carcinoma includes a large number of specific
      quasispecies presumably due to their vigorous proliferation. A different set of
      quasispecies with the amino acid change is presumed to be related to the
      hepatocarcinogenesis.

PMID- 8579574
TI  - A stable phage-display system using a phagemid vector: phage display of hen egg
      white lysozyme (HEL), Escherichia coli alkaline, phosphatase, and anti-HEL
      monoclonal antibody, HyHEL10.
AB  - A stable expression system for displaying the pIII fusion protein on the surface
      of a filamentous phage was constructed. A phagemid pIII display vector, pLUCK,
      was constructed by inserting the gene encoding the pIII fusion protein in the
      opposite direction to that of the lac promoter of pTZ18U. Using this phage
      display system, two enzymes, hen egg-white lysozyme (HEL) and E. coli alkaline
      phosphatase, and the single-chain Fv fragment of anti-HEL monoclonal antibody
      HyHEL10, could be stably and functionally displayed. Northern and primer
      extension analyses showed that a small amount of the sense mRNA encoding pIII
      fused HEL was transcribed from the minor phage promoter located in the region
      encoding the C-terminus of pIII. Repressed expression of the pIII fusion protein
      can lead to the display of a wide range of proteins on filamentous phages without
      the need for strict expression conditions.

PMID- 8579575
TI  - Sonic hedgehog is expressed in epithelial cells during development of whisker,
      hair, and tooth.
AB  - Sonic hedgehog (Shh) is a vertebrate gene homologous to a Drosophila segment
      polarity gene, hedgehog, and functions as a secreted signaling molecule in limb
      pattern formation, differentiation of motor neurons, and sclerotome induction. We
      found that Shh is also expressed in epithelia of the developing whisker, hair,
      tooth, rugae, and thyroid primordium of mouse embryos. In whisker and hair
      development, Shh is expressed in epithelial cells before condensation of the
      underlying mesenchymal cells and then in the placode. The expression of Shh
      continues in the hair bulb surrounding the dermal papilla. Shh is also expressed
      in epithelial cells of the tooth bud, then localized to the enamel knot. The Shh
      expression continues in developing ameloblasts. These results suggest that SHH is
      an essential epithelial signaling molecule in epithelio-mesenchymal interactions
      for the terminal differentiation.

PMID- 8579577
TI  - Nitric oxide stimulates the activity of a 72-kDa neutral matrix metalloproteinase
      in cultured rat mesangial cells.
AB  - We recently demonstrated that stimulation of inducible nitric oxide synthase
      (iNOS) activity reduced the accumulation of collagen and fibronectin in cultured
      rat mesangial cells. Therefore, we examined whether nitric oxide (NO) influenced
      the activity of a 72 kDa neutral matrix metalloproteinase by these cells in
      vitro. Enzyme activity was assessed in a biotin-avidin ELISA and by zymography.
      Exposure of mesangial cells to the cytokines, interferon (IFN)-gamma and
      lipopolysaccharide (LPS), increased gelatinolytic activity by 325 +/- 60% (P <
      0.025). Co-incubation with 20 mM L-arginine caused a further increase in matrix
      metalloproteinase levels. Addition of L-NAME, an inhibitor of iNOS, reversed the
      IFN-gamma/LPS-induced rise in gelatinolytic activity. Incubation with the
      exogenous NO donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), resulted in a
      dose dependent increase in metalloproteinase activity (P < 0.01). The NO-induced
      changes in metalloproteinase activity were also demonstrable by zymography. These
      data indicate that NO modulates the activity of a 72 kDa neutral matrix
      metalloproteinase and suggest that altered NO production may contribute to the
      development of glomerulosclerosis and tubulointerstitial fibrosis in chronic
      renal disease states.

PMID- 8579576
TI  - Specific expression in brain and liver driven by the hemopexin promoter in
      transgenic mice.
AB  - Transgenic mice harboring the human hemopexin promoter sequences linked to the
      lacZ reporter gene were generated and analyzed for temporal and spatial
      distribution of beta-galactosidase. Upstream sequences spanning from -1800, -700
      and -500 bp to the transcription start point direct regulated beta-galactosidase
      expression specifically to the liver and to the brain of transgenic mice. These
      results suggest that the 500 bp DNA fragment flanking the 5'end of the human
      hemopexin gene contains the cis-acting elements required for tissue and
      developmental stage-specific expression in vivo and provide evidence for a new
      extrahepatic site of expression of the hemopexin gene.

PMID- 8579578
TI  - Cross-linking of the ninth consensus repeat domain of P-selectin (GMP-140, CD62P)
      with a monoclonal antibody enhanced leukocyte adhesive activity.
AB  - P-selectin (GMP-140, CD62P) is a member of the selectin family of cell adhesion
      molecules expressed on the cell surface of platelets and endothelial cells, which
      mediates leukocyte adhesion via carbohydrate ligands. We now report that a
      monoclonal antibody (mAb), recognizing the ninth consensus repeat domain of the
      human P-selectin molecule, enhanced the adhesion activity of neutrophils to
      platelets, whereas the monovalent Fab fragment of the mAb did not exert this
      effect. The enhancement by the mAb was thought to result from cross-linking of
      the P-selectin molecules. The results indicated that cross-linking adjacent to
      the transmembrane domain of P-selectin enhanced the cell adhesion activity.

PMID- 8579579
TI  - Cloning, chromosomal localization, and tissue expression of autotaxin from human
      teratocarcinoma cells.
AB  - Autotaxin, a potent human tumor cell motility-stimulating exophosphodiesterase,
      was isolated and cloned from the human teratocarcinoma cell line NTera2D1. The
      deduced amino acid sequence for the teratocarcinoma autotaxin has 94% identity to
      the melanoma-derived protein, 90% identity to rat brain phosphodiesterase
      I/nucleotide pyrophosphatase (PD-I alpha), and 44% identity to the plasma cell
      membrane marker PC-I. Utilizing polymerase chain reaction screening of the CEPH
      YAC library, we localized the autotaxin gene to human chromosome 8q23-24.
      Northern blot analysis of relative mRNA from multiple human tissues revealed that
      autotaxin mRNA steady state expression is most abundant in brain, placenta,
      ovary, and small intestine.

PMID- 8579580
TI  - Separation of H7-resistant protein kinase C isoforms from gonadotroph-derived
      alpha T3-1 cells.
AB  - Certain physiological events in anterior pituitary tissue are regulated by
      protein kinase C that is relatively resistant to the inhibitor, H7. In the
      present studies we have shown that two H7-resistant protein kinase C activities
      may be isolated from (pituitary) gonadotroph-derived alpha T3-1 cells using
      hydroxyapatite chromatography. These activities have the characteristics of PKC
      zeta and an apparently novel PKC isoform. The availability of clonal alpha T3-1
      cells will facilitate investigations of the pituitary events.

PMID- 8579581
TI  - Molecular cloning of a novel cytoplasmic protein tyrosine phosphatase PTP
      epsilon.
AB  - We have isolated a cDNA of a novel cytoplasmic variant of the protein tyrosine
      phosphatase epsilon (PTP epsilon) from rat spleen cDNA library. Its deduced amino
      acid sequence of 642 residues was 94.6% identical to C-terminal 642 residues of
      human PTP epsilon (HPTP epsilon). However, N-terminal 12 amino acid residues of
      the rat PTP epsilon had no homology to HPTP epsilon. The unique N-terminal
      sequence of the rat PTP epsilon was shorter and much more hydrophilic than the
      transmembrane domain of HPTP epsilon. These results strongly suggest that the rat
      PTP epsilon, designated here as PTP epsilon C, is a novel cytoplasmic PTP with
      two tandem catalytic domains. We also isolated by RT-PCR a rat transmembrane PTP
      epsilon cDNA, designated as PTP epsilon M, which has the extracellular and
      transmembrane domains in addition to the common sequence to the PTP epsilon C.
      These results suggested that the PTP epsilon C and PTP epsilon M are generated
      from a single gene and may be involved in multiple functions in signal
      transduction.

PMID- 8579582
TI  - In vivo role of the Sp1 site neighboring sterol-responsive element-1 in
      controlling low-density lipoprotein receptor gene expression.
AB  - The in vivo role of the crucial Sp1 site neighboring sterol-responsive element-1
      (SRE-1) in controlling LDL receptor gene expression in the presence or absence of
      sterols was examined. For this purpose the Xenopus laevis system was utilized as
      there are two different genes for LDL receptors in frogs which differ in their
      promoter region in the Sp1-binding sequence of repeat 3 present immediately
      adjacent to SRE-1. DNase I footprinting of promoters of both receptors showed
      differences in the affinity of this Sp1 site to purified transcription factor
      Sp1. Transcript levels of both LDL receptors were measured in livers of frogs on
      normal and cholesterol-enriched diets. Basal levels and extent of repression of
      LDL receptor gene on sterol administration were found to be dependent on the
      nature of the Sp1 site of repeat 3 under in vivo conditions. We conclude that
      this Sp1 site acts as a constitutive positive transcriptional element that forms
      a part of the active transcription complex irrespective of cellular sterol
      levels.

PMID- 8579583
TI  - The uncoupling of Shc activation from distal intracellular signalling in a cell
      line which expresses a truncated human epidermal growth factor receptor.
AB  - We have examined epidermal growth factor (EGF) signalling in a CHO cell line
      (CHO11) which expresses a human EGF receptor truncated at amino acid 990.
      Previous studies showed that EGF treatment of these cells failed to increase
      prostaglandin production or phospholipase A2 activity. In the current study EGF
      increased the tyrosine phosphorylation of the intracellular signalling protein
      Shc in CHO11 cells but did not activate either of the downstream signalling
      enzymes raf or mitogen activated protein kinase (MAPK). The uncoupling of Shc
      activation from distal signalling in CHO11 cells contrasts with other cells which
      express similar mutant EGF receptors. The failure of She to activate distal
      signalling may reflect qualitative differences in the way that this protein is
      activated or could result from the activation of an inhibitory signalling
      pathway.

PMID- 8579584
TI  - Activation of large conductance Ca(2+)-activated K+ channels in N1E-115
      neuroblastoma cells by platelet-activating factor.
AB  - Using patch-clamp single channel recording techniques, we reported a Platelet
      Activating Factor "PAF"-induced activation of large conductance Ca(2+)-activated
      K+ "BK(Ca)" channels in N1E-115 cells. This activation was only observed in cell
      attached configuration and was blocked by the PAF antagonist BN50739 or removal
      of calcium from the bath. Nanomolar concentration of PAF produced a transient
      hyperpolarization observed in whole-cell current clamp configuration which was
      blocked by the bath application of BN50739 or iberiotoxin. Our results suggest
      that the PAF-induced hyperpolarization is mediated by an activation of BK(Ca)
      channels coupled to specific PAF receptors. This coupling is not direct and
      results from the PAF-induced elevation in cytosolic free Ca2+ concentrations that
      we have previously described in N1E-115 cells (Cell Calcium 1995, 17, 442-452).

PMID- 8579585
TI  - Physiological role of nitric oxide as an enhancer of oxygen transfer from
      erythrocytes to tissues.
AB  - The present study revealed the physiological role of NO as an enhancer of oxygen
      release from erythrocytes to peripheral tissue by breaking or stretching the heme
      iron-proximal histidine bond in the alpha subunit of hemoglobin (Hb), while
      maintaining oxygen binding capacity by restoring the bond in the lungs. Oxygen
      affinity was significantly decreased in blood containing NO-bound Hb alpha. The
      results may partly explain nitrosothiols in blood as an NO reservoir for an
      emergency and why cytokines induce NO synthase in the vascular system during such
      events as inflammation.

PMID- 8579586
TI  - Cytosine arabinoside differentially alters survival and neurite outgrowth of
      neuronal PC12 cells.
AB  - Cytosine arabinoside, a potent antimitotic agent, is used clinically as an
      anticancer drug with the side effect of severe neurotoxicity. Earlier reports
      suggested that this agent blocks the signaling pathway of nerve growth factor in
      sympathetic neurons, which results in neuronal death. The present study
      demonstrated that neuronal PC12 cells deprived of nerve growth factor showed a
      decrease of neurite outgrowth, which was not seen in cytosine arabinoside-treated
      neuronal PC12 cells, suggesting that this agent may not interfere with the part
      of the NGF signaling pathway that leads to neurite outgrowth. On the other hand,
      treatment of neuronal PC12 cells with cytosine arabinoside led to a dose- and
      time-dependent decrease of viability. These results suggest that there is a
      distinction between the neurite outgrowth and the survival promoting activities
      of nerve growth factor.

PMID- 8579587
TI  - Downregulation of the human heme oxygenase gene by glucocorticoids and
      identification of 56b regulatory elements.
AB  - Several human heme oxygenase-1 promoter-driven chloramphenicol acetyltransferase
      constructs were examined in order to analyze promoter activity of the heme
      oxygenase-1 gene in microvessel endothelial cells. Heme oxygenase promoter
      activity was up-regulated by interleukin-6. This induction was shown to be down
      regulated by glucocorticoids. Chloramphenicol acetyltransferase assays revealed
      that the promoter region (56 base pair) between -180 and -120 was responsible for
      up-regulation by growth factors, as well as for glucocorticoid-directed down
      regulation. The same DNA fragments was shown to bind nuclear factor(s) from
      endothelial cells treated with dexamethasone. Formation of DNA protein complexes
      peaked after a 6-hour treatment. The DNA fragment was found to contain a sequence
      recognized by the STAT 3/acute phase response factor.

PMID- 8579588
TI  - Correction of the galactocerebrosidase deficiency in globoid cell leukodystrophy
      cultured cells by SL3-3 retroviral-mediated gene transfer.
AB  - Globoid cell leukodystrophy (GCL) or Krabbe disease is an autosomal recessive
      inherited disease caused by the deficiency of galactocerebrosidase, the lysosomal
      enzyme responsible for the degradation of galactocerebroside, a major component
      of myelin. An animal model homologue of GCL is the twitcher mouse. In the present
      work, using novel recombinant retroviruses harboring the SL3-3 LTR, we have been
      able to stably correct the galactocerebrosidase deficiency in twitcher mouse TM-2
      cells and in primary human fibroblasts from a patient with globoid cell
      leukodystrophy. These results show the possibility of retroviral-mediated gene
      therapy for the treatment of GCL.

PMID- 8579589
TI  - 4-Hydroxynonenal triggers Ca2+ influx in isolated rat hepatocytes.
AB  - Addition of micromolar concentrations of 4-hydroxynonenal (4-HNE), a reactive end
      product of lipid peroxidation, to isolated rat hepatocytes was found to cause an
      early and transient increase in cytosolic Ca2+ concentration followed by a more
      pronounced and progressive elevation. Such a late effect of 4-HNE was prevented
      by chelation of extracellular Ca2+ with EGTA or by the addition of GdCl3, which
      is known to block the activity of store operated Ca2+ channels in the hepatocyte
      plasma membrane. Moreover, the preincubation of isolated hepatocytes with the
      phospholipase C inhibitor U73122 resulted in a complete inhibition of both the
      early increase of cytosolic Ca2+ and the subsequent Ca2+ inflow. When 4-HNE was
      added to the hepatocytes 5 min after the emptying of intracellular Ca2+ pools by
      thapsigargin, the aldehyde caused a further increase in the accumulation of Ca2+
      which was prevented in the presence of GdCl3. Taken together these results
      indicate that in hepatocytes 4-HNE causes Ca2+ inflow across GdCl3-sensitive Ca2+
      channels. The mechanism responsible for such an effect is triggered by the
      emptying of intracellular Ca2+ pools likely resulting from 4-HNE mediated
      stimulation of phospholypase C, but 4-HNE also appears to interfere with the
      channel protein(s) or with the mechanism(s) regulating capacitative Ca2+ inflow.

PMID- 8579590
TI  - Induction of the adipose differentiation-related protein in liver of etomoxir
      treated rats.
AB  - The effects of etomoxir, an irreversible carnitine palmitoyltransferase I
      inhibitor, on the liver protein pattern and on liver morphology were examined by
      two-dimensional gel electrophoresis in female Sprague-Dawley rats treated with
      125 mg/kg/day etomoxir for 28 days. In livers of treated animals a protein spot
      was found which was not present in controls. The spot was identified by internal
      amino acid sequence analysis as the adipose differentiation-related protein
      (ADRP). The expression of ADRP in liver is a novel finding as the protein has
      been described previously as adipocyte-specific. Additionally we found
      histopathologic evidence of lipid accumulation in the livers of etomoxir rats.
      The data show that for each treated rat there was a good correlation between ADRP
      levels and degree of lipid droplet formation. This observation may suggest a
      potential relationship between drug-induced expression of ADRP in liver and lipid
      accumulation.

PMID- 8579591
TI  - Cloning and chromosomal localization of the human P2Y1 purinoceptor.
AB  - We have isolated two types of human P2Y1 cDNA clones from the human erythro
      leukemia cell cDNA library. The sequence of both clones codes for the same 373
      amino acid polypeptide and these clones differ only in the length of the 3'
      untranslated region. The long form of the cDNA has 1165 nt 3' untranslated region
      while the 3' untranslated region in the short form is only 258 nt. Both forms
      are, however, polyadenylated. A multiple human tissue northern blot indicated two
      transcripts of approximately 4.4 kb and 7.0 kb. The 4.4 kb mRNA is present in all
      the eight tissues, while the approximately 7.0 kb transcript is expressed only in
      placenta, skeletal muscle, and pancreas. Using oligonucleotide primers specific
      for the human P2Y1 purinergic receptor to amplify a region from genomic DNA from
      a panel of mouse/human somatic cell hybrid cell lines, we have localized the P2Y1
      gene to human chromosome 3.

PMID- 8579592
TI  - Expression and regulation by insulin of GLUT 3 in UMR 106-01, a clonal rat
      osteosarcoma cell line.
AB  - Expression of the glucose transporter GLUT 3 is mainly restricted to neuronal
      tissues, with lower levels in testis and placenta. In addition, GLUT 3 has
      recently been reported in neonatal rat calvaria by in situ hybridisation. We
      report the co-expression of GLUT 1 and GLUT 3 mRNA and protein in UMR 106-01, a
      clonal osteosarcoma cell line. By semi-quantitative analysis we show that GLUT 3
      protein is expressed at levels comparable to GLUT 1. Insulin stimulates glucose
      uptake in UMR 106-01 cells. GLUT 3 mRNA and protein are increased by chronic (16
      h) treatment with insulin, and the increase in GLUT 3 mRNA is not inhibited by
      cycloheximide. Regulation of GLUT 3 mRNA by insulin has not been previously
      shown. UMR 106-01 represents a useful model for investigating regulation of GLUT
      3 expression.

PMID- 8579593
TI  - Transfecting well-differentiated prostatic cancer cell line LNCaP.
AB  - The transfection of well-differentiated sensitive cells requires careful
      optimization of the conditions used. In addition to the transfection method
      chosen, the amount of cells plated, and thus the density of the cells, as well as
      the influence of the serum concentration play a critical role in the case of
      LNCaP cells. We also found out that the only appropriate control plasmid for the
      transfection efficiency was pCMV beta-gal driven by the cytomegalovirus promoter.

PMID- 8579594
TI  - In vitro reconstitution of apolipoprotein B RNA editing activity from recombinant
      APOBEC-1 and McArdle cell extracts.
AB  - Apolipoprotein B (apoB) RNA editing activity involves a site-specific cytidine to
      uridine transition catalyzed by a cytidine deaminase, APOBEC-1, in the context of
      a multi-protein-containing editosome. In the absence of yet to be characterized
      "auxiliary" proteins, APOBEC-1 lacks RNA editing capacity. Recombinant APOBEC-1
      has been engineered to bind nickel resin and used in affinity chromatography of
      the auxiliary proteins from McArdle rat hepatoma cell extracts. We demonstrate
      activation of APOBEC-1 RNA editing activity under these conditions through the
      association of a subset of extract proteins having approximate molecular masses
      of 145, 87, 75, 66, 61, and 50 kDa and a heterogeneous grouping of 45- to 35-kDa
      proteins. These data suggest that the components of the editosome can be
      partially purified from extracts through APOBEC-1 affinity chromatography.

PMID- 8579595
TI  - High-level expression of human inducible nitric oxide synthase in Chinese hamster
      ovary cells and characterization of the purified enzyme.
AB  - Chinese hamster ovary cells were transfected with the human inducible nitric
      oxide synthase (iNOS) cDNA under the control of the hCMV promoter. The NOS
      inhibitor, S-ethyl isothiourea, was utilized to minimize toxicity from NO
      production. Selected colonies were grown in the absence of S-ethyl isothiourea,
      after which nitrite levels in the medium were measured. NOS activities in cell
      lysates were determined, and 9 colonies had iNOS activities of over 1 nmol of
      citrulline formed/min/mg protein. iNOS expression was further increased by gene
      amplification and the use of sodium butyrate, resulting in two cell lines with
      stable activity of greater than 3 nmol/min/mg. The iNOS purified from these cells
      had a specific activity of over 500 nmol/min/mg, and its properties were similar
      to native iNOS purified from cytokine-induced DLD-1 cells. This is the most
      efficient expression system reported to date for iNOS.

PMID- 8579596
TI  - Tyrosine kinase inhibitors, genistein and herbimycin A, do not block interleukin
      1 beta-induced activation of NF-kappa B in rat mesangial cells.
AB  - We have previously demonstrated that interleukin-1 beta (IL-1 beta) rapidly
      induces tyrosine phosphorylation of several proteins in the renal mesangial cell.
      Two mechanistically distinct tyrosine kinase inhibitors, genistein and herbimycin
      A, block the induction of cyclooxygenase-2 (COX-2) and inducible nitric oxide
      synthase (iNOS) by IL-1 beta in rat mesangial cells. Since both COX-2 and iNOS
      promoters have a kappa B binding motif, we have evaluated the effects of tyrosine
      kinase inhibitors on IL-1 beta-induced nuclear factor-kappa B (NF-kappa B)
      activation by electromobility shift assays. IL-1 beta rapidly induced the
      translocation of NF-kappa B in rat mesangial cells. However, the tyrosine kinase
      inhibitors, genistein and herbimycin A, failed to block the translocation of NF
      kappa B at concentrations which abolish COX-2 and iNOS mRNA expression. These
      data suggest that an upstream tyrosine kinase pathway may not be required for IL
      1 beta-induced NF-kappa B activation and that the tyrosine kinase pathway may
      converge with the NF-kappa B pathway down-stream of NF-kappa B activation in rat
      mesangial cells.

PMID- 8579597
TI  - Molecular cloning and characterization of a putative novel human osteoclast
      specific 116-kDa vacuolar proton pump subunit.
AB  - A cDNA encoding a possible novel human 116-kDa polypeptide subunit of the
      osteoclastic proton pump (OC-116KDa) has been identified by differential
      screening of a human osteoclastoma cDNA library. The predicted sequence of OC
      116kDa consists of 822 amino acids and is 46.9% and 47.2% identical at the amino
      acid level to the 116-KDa polypeptide of the vacuolar proton pump of rat and
      bovine brain respectively. OC-116KDa mRNA was found at high levels in
      osteoclastomas by Northern analysis but was not detected in tumor stromal cells
      or in other tissues including kidney, liver, skeletal muscle and brain. OC-116KDa
      mRNA was localized to multinucleated giant cells within the osteoclastoma tumor
      by in situ hybridization.

PMID- 8579598
TI  - The ubiquitously expressed pICln protein forms homomeric complexes in vitro.
AB  - Endothelial cells contain a cell-volume sensitive chloride conductance with
      biophysical properties similar to those of a ubiquitously expressed chloride
      current that is activated by cell swelling. The latter current has been
      associated with the ICln protein (pICln) which may be the chloride channel itself
      or, alternatively, a channel regulator. We were therefore interested in whether
      pICln is involved in the endothelial volume-sensitive chloride current. As a
      first step, we have cloned human pICln and studied its expression at the protein
      level. Using a polyclonal antiserum raised against human pICln we found a
      widespread expression of pICln, both in endothelial cells and in other cell
      lines. A characteristic feature of pICln is its anomalous migration during
      denaturing polyacrylamide gel electrophoresis. We also demonstrate that
      bacterially expressed pICln forms homomeric complexes in vitro.

PMID- 8579599
TI  - The effect of juglone on the membrane potential and whole-cell K+ currents of
      human lymphocytes.
AB  - Using flow cytometric membrane potential measurements with the oxonol dye, we
      determined that 5.7-57 microM juglone depolarizes human lymphocytes in a dose
      dependent manner. The depolarizing effect of juglone was verified by patch-clamp.
      Juglone decreased whole-cell n-type K+ currents in human peripheral blood
      lymphocytes and accelerated inactivation; however, it did not influence the
      kinetics of activation of the K+ conductance. The percentage increase in K+
      channel inactivation rate and the degree of drug induced block was independent of
      membrane potential, K+ channel block by juglone fully developed within 4 minutes
      and was not removable by washing with drug free extracellular solution. Blocking
      of n-type K+ channels by juglone is in concert with its depolarizing effect on
      human lymphocytes.

PMID- 8579600
TI  - Identification of porin as a binding site for MAP2.
AB  - Porin or VDAC, the pore forming protein in the outer mitochondrial membrane, was
      identified as a binding site for microtubule-associated protein 2 (MAP2). By
      affinity chromatography using covalently bound MAP2, two proteins were
      selectively purified with molecular weights 63 and 70 KD. The 63 KD protein was
      identified to be the dimer of porin using affinity purified porin antibodies.

PMID- 8579601
TI  - Increase of empty pool-activated Ca2+ influx using an intracellular Ca2+
      chelating agent.
AB  - We demonstrate here that stimulated 45Ca2+ influx in A7r5 vascular smooth muscle
      cells induced either by receptor activation with [Arg]8 vasopressin or by the SR
      Ca(2+)-ATPase inhibitor thapsigargin was increased more than threefold if cells
      were preloaded with the intracellular calcium chelator BAPTA (1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). The increased influx is probably
      due to an attenuation of negative feedback of Ca2+ on its own entry accompanied
      by increased Ca2+ storage capacity of BAPTA-loaded cells leading to diminished
      cellular Ca2+ release. We propose that BAPTA preloading could be a useful
      approach to investigate receptor-induced Ca2+ influx.

PMID- 8579602
TI  - Lysine 173 residue within the first exoloop of rat secretin receptor is involved
      in carboxylate moiety recognition of Asp 3 in secretin.
AB  - The contribution of the extracellular loops of the secretin receptor to the
      recognition of secretin was investigated by transfection in CHO cells of chimeric
      receptors, in which the three loops of the secretin recombinant receptor were
      replaced by the corresponding sequences of the glucagon receptor. The role of the
      third loop could not be evaluated as the transfected cells did not respond to
      secretin. Replacement of extracellular loop 2 reduced markedly the capability of
      secretin to occupy the receptor but did not alter the capacity of the receptor to
      discriminate between peptide analogues modified in position 3. Replacement of the
      first extracellular loop not only reduced the potency of secretin but also
      decreased the capacity of the receptor to discriminate between ligands having in
      position 3 an aspartate (as in secretin), an asparagine, or a glutamic acid. This
      change in receptor properties was reproduced by a single mutation of lysine 173
      of the receptor into isoleucine. Thus, the basic amino acid in position 173 is
      likely to interact with aspartate 3 of secretin. As an aspartate is also present
      in position 3 of VIP and PACAP, two peptides related to secretin, and a lysine
      residue is conserved in the first extracellular loop of the VIP and PACAP
      receptors, this interaction may be a key element of peptide recognition by this
      receptor family.

PMID- 8579603
TI  - Involvement of vicinal dithiols in differential regulation of fMLP and phorbol
      ester-activated phospholipase D in stimulated human neutrophils.
AB  - In the human neutrophil, the fMLP-activated phospholipase D (PLD) was entirely
      calcium and tyrosine kinase dependent, but protein kinase C independent. An
      opposite regulation was observed with phorbol ester PMA, since the phospholipase
      D activity was mostly calcium insensitive, tyrosine kinase independent, but
      protein kinase C dependent. The arsenical compound, phenylarsine oxide (PAO),
      which reacts with vicinal sulhydryl groups, activated twofold at one minute the
      PMA stimulated-PLD activity, whereas it inhibited half of the fMLP-activated PLD
      after a time lag of 30 sec. Our data indicate that PAO acted on a mechanism
      regulating the balance between fMLP-activated and PMA-activated phospholipase D
      activity. Noteworthy, PAO similarly inhibited fMLP and PMA-induced O2(-)
      production.

PMID- 8579604
TI  - Studies of the calmodulin-binding site of twitchin with synthetic peptides using
      fluorescence and CD spectroscopy.
AB  - The calcium-dependent interaction of two synthetic peptides derived from the
      putative calmodulin-binding site in the protein kinase autoinhibitory region of
      twitchin was studied by fluorescence and CD spectroscopy. The peptides interacted
      with dansylcalmodulin in the presence of Ca2+ as shown by a change in the
      fluorescence emission spectra. Fluorescence titration of dansylcalmodulin with
      the peptides was used to quantify this interaction. The peptides appeared to
      assume a helical conformation in a non-polar environment as seen by CD
      spectroscopy. The ellipticity of Ca2+ calmodulin was enhanced in the presence of
      peptides compared with that of Ca2+ calmodulin and peptides alone, indicating
      that the peptides had formed a complex with calmodulin. These results support the
      assignment of the twitchin calmodulin-binding site.

PMID- 8579605
TI  - Sequences in the myosin II tail required for self-association.
AB  - The assembly of myosin II molecules into a filament requires the electrostatic
      interaction of a domain localized toward the carboxyl-terminus of the myosin II
      tail. However, the precise sequences involved in this interaction are not known.
      Here we show that the smallest Dictyostelium myosin II fragment that is necessary
      and sufficient for self-association is a fragment of 294 amino acids that
      contains four clusters of positively charged and negatively charged residues.
      Fragments of the same length but which lack one of these positively or negatively
      charged clusters are incapable of self-assembly. We postulate that this assembly
      domain is also found in myosin II from other species. Such charged clusters are
      found in a similar location in rabbit myosin II and are also essential for
      filament formation.

PMID- 8579606
TI  - Calcitonin prevents CCl4-induced hydroperoxide generation and cytotoxicity
      possibly through C1b receptor in rat hepatocytes.
AB  - The effects of calcitonin (CT) on oxyradical generation and cellular damage
      induced by carbon tetrachloride (CCl4) were investigated in rat hepatocytes.
      Addition of CCl4 to the cells concentration dependently increased intracellular
      production of hydroperoxides and release of aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT). The hepatocytes expressed mRNA for a CT receptor,
      C1b. Coaddition of CT to the cells concentration dependently suppressed the CCl4
      induced increase in hydroperoxide production and also decreased the release of
      AST and ALT. The suppressive effect of CT on hydroperoxide production was
      reversed by further addition of H7 or by pretreatment with phorbol 12-myristate
      13-acetate for 24 h. These results suggest that CT prevents CCl4-induced
      oxyradical production and cellular damage through activation of protein kinase C
      in hepatocytes.

PMID- 8579607
TI  - Sphingosine transfer in cell-to-cell interaction.
AB  - We have investigated possible intercellular transfer of Sph between heterogeneous
      and homogeneous cells, utilizing different abilities on conversion of Sph into
      GlcCer. Murine IL-2-dependent T lymphocyte CTLL cells metabolize exogenously
      added Sph to GlcCer through Cer within 30 min, whereas fibroblast BALB/C A31
      cells required more than 2 h. Thus, CTLL cells exhibiting the active conversion
      were used as recipient cells, whereas A31 cells where the conversion was slow and
      fumonisin B1 (inhibition of Cer biosynthesis)-treated CTLL cells being donor
      cells. To test intercellular transfer of Sph, donor cells incorporated
      radioactive Sph were coincubated with CTLL cells and GlcCer was examined. The
      present experiments described the possible transfer of Sph between heterogeneous
      (from A31 cells to CTLL cells) and homogeneous cells (from fumonisin B1-treated
      CTLL cells to CTLL cells).

PMID- 8579608
TI  - Tissue distribution of opioid receptor gene expression in the rat.
AB  - The endogenous opioid peptides have multiple physiological actions at both a
      central and peripheral level which are mediated by 3 main classes of opioid
      receptors, mu, delta and kappa. The rat mu, delta and kappa opioid receptors have
      recently been cloned and their distribution of expression in the central nervous
      system has been mapped. In these studies we have used the reverse transcriptase
      polymerase chain reaction and Southern blotting to determine the distribution of
      expression of the mu, delta and kappa opioid receptors in the peripheral tissues
      of the rat. All 3 opioid receptors were found to be widely expressed in several
      peripheral tissues including the small intestine, large intestine, adrenal,
      kidney, lung, spleen, testis, ovary and uterus. In the stomach, delta and kappa
      but not mu opioid receptor transcripts were detected. Predominantly delta
      transcripts were detected in the heart, with no mu and only a weak signal for the
      kappa receptor. In the liver mu and delta but not kappa transcripts were present.
      Opioid receptor expression was not detected in endothelium or synovium. There is
      therefore a broad, but tissue specific distribution of opioid receptor expression
      in the periphery of the rat, suggesting that the endogenous opioid peptides play
      an endocrine, paracrine, or autocrine role in the regulation of physiology at a
      peripheral as well as central level.

PMID- 8579609
TI  - Functional characterization of a 1,25-dihydroxyvitamin D3 receptor binding site
      found in the rat atrial natriuretic factor promoter.
AB  - The classical action of the hormone 1,25-dihydroxyvitamin D3 (VD) is the
      regulation of calcium metabolism. In contrast, the peptide hormone atrial
      natriuretic factor (ANF) is one of the few known nonclassical VD responding
      genes. We screened the promoter of the rat ANF gene and identified a typical VD
      receptor (VDR) binding site formed by a direct repeat of two hexameric core
      binding motifs spaced by three nucleotides, between positions -907 and -891. Like
      most of the DR3-type VD response elements this sequence is bound with high
      affinity (Kd = 0.53 nM) by a heterodimer formed by VDR and retinoid X receptor.
      In a heterologous promoter context one copy of this sequence mediated an about
      fourfold gene activation by VD and a half-maximal activation (EC50) value of 0.48
      nM VD. This characterizes the identified sequence as one of the most potent VD
      response elements.

PMID- 8579610
TI  - A novel function for nucleoside diphosphate kinase in Drosophila.
AB  - Nucleoside diphosphate (NDP) kinase is an enzyme that transfers the gamma
      phosphate of nucleoside triphosphates to nucleoside diphosphates. Besides this
      well-defined role, recent evidence suggests that NDP kinase may be implicated in
      a wide variety of essential cellular processes. In this paper, we showed that the
      NDP kinase of Drosophila exhibited protein kinase activity as well as
      autophosphorylation. Ovalbumin was phosphorylated with guanosine 5'-(3-O
      thio)triphosphate (GTP gamma S) or ATP. Protein kinase activity was not detected
      in NDP kinase mutant, abnormal wing discs (awd). These results suggest that this
      activity could be one of the functions of NDP kinase essential for normal fly
      development, since awd gene is lethal.

PMID- 8579611
TI  - Calcium ionophore induced proteolysis and cataract: inhibition by cell permeable
      calpain antagonists.
AB  - Two dipeptide aldehyde cell permeable calpain inhibitors, cBz-Val-Phe and
      calpeptin, have been assessed for their ability to prevent cytoskeletal
      proteolysis and loss of transparency in whole rat lenses. Calcium overload,
      induced by ionomycin in artificial aqueous humor with 1mM calcium, resulted in
      lens opacification and degradation of cytoskeletal proteins including spectrin,
      filensin, and vimentin. No such changes resulted from incubation in ionomycin in
      the absence of calcium. In calcium overload lenses both inhibitors gave some
      protection against cytoskeletal protein degradation and loss of transparency.
      These experiments indicate that calpain has a role in cortical opacification in
      high calcium lenses and that cell penetrating calpain inhibitors do indeed enter
      lens cells and reduce both proteolysis and opacification.

PMID- 8579612
TI  - Synthesis and purification of soluble ligand binding domain of the human vitamin
      D3 receptor.
AB  - We expressed and purified milligram quantities of the ligand binding domain of
      the human 1,25-dihydroxyvitamin D3 receptor using a glutathione-S-transferase
      (GST) fusion protein expression system. Amino acids 105-427 were expressed in E.
      coli as a GST fusion protein at a reduced (20 degrees C) temperature and purified
      on glutathione sepharose. The fusion protein adsorbed to glutathione sepharose
      was cleaved with thrombin to yield soluble 105-427 human 1,25-dihydroxyvitamin D3
      receptor. The 105-427 human 1,25-dihydroxyvitamin D3 receptor was further
      purified by Mono Q ion exchange chromatography and was characterized as a single
      band on SDS-polyacrylamide gel electrophoresis. The 105-427 human 1,25
      dihydroxyvitamin D3 receptor bound 1,25-dihydroxyvitamin D3 with high affinity
      (Kd approximately 10(-9)M) and with a binding capacity of 47 pmoles/nmole
      protein. Large scale expression of 105-427 human 1,25-dihydroxyvitamin D3
      receptor will provide human 1,25-dihydroxyvitamin D3 receptor ligand binding
      domain suitable for structural studies.

PMID- 8579613
TI  - Biodegradation of polychlorinated biphenyls by rhizobia: a novel finding.
AB  - Metabolism of simple aromatic compounds in rhizobial strains has been a subject
      of study for a few decades, due either to the significance of nutritional
      diversity in the inoculum survival during agricultural applications or to the
      importance of plant phenolics in the microbe-plant cross-talk and signal
      transduction. Here, we report the capability of rhizobial strains to catabolize
      polychlorinated biphenyls (PCBs). In order to identify the genes in these strains
      that mediate the catabolism of PCBs we used the bphABC genes from Comamonas
      testosteroni strain B-356. Our results showed that genomic DNAs from all four
      rhizobial strains studied hybridized strongly with the Comamonas-derived probe,
      indicating the presence of a similar genetic system. This is a novel and
      interesting finding indicating for the first time, perhaps, of a role of rhizobia
      in recycling of aromatic compounds in nature and, certainly, opening a new avenue
      to be explored in the field of bioremediation.

PMID- 8579614
TI  - Purification and cloning of a soluble ATP-diphosphohydrolase (apyrase) from
      potato tubers (Solanum tuberosum).
AB  - A soluble ATP-diphosphohydrolase (apyrase, EC 3.6.1.5) has been purified from
      potato tubers. Solanum tuberosum, to a specific activity of 10,000 mumol
      P(i)/mg/min. The cDNA corresponding to the potato apyrase has been isolated and
      termed RROP1. The deduced amino acid sequence contains a putative signal
      sequence, two hydrophobic regions at the carboxy terminus, two potential Asn
      linked glycosylation sites, and four regions in the amino-terminal half that we
      term ACR (apyrase conserved regions) 1-4 that are highly conserved in known
      apyrases and related enzymes; garden pea nucleoside triphosphatase, Toxoplasma
      gondii nucleoside triphosphate hydrolases, and Saccharomyces cerevisiae golgi
      guanosine diphosphatase. A yeast 71.9-kDa hypothetical protein on chromosome V, a
      Caenorhabditis elegans hypothetical 61.3-kDa protein on chromosome III, and human
      CD39, a lymphoid cell activation antigen, also share the conserved ACR regions,
      but their ability to hydrolyze nucleotides has not been assessed.

PMID- 8579615
TI  - Cloning and expression in Xenopus oocytes of a mouse homologue of the human
      acylcoenzyme A: cholesterol acyltransferase and its potential role in metabolism
      of oxidized LDL.
AB  - We used a Xenopus oocyte expression system to screen a mouse macrophage cDNA
      library for receptors for oxidized LDL (OxLDL). Injection of unfractionated mouse
      macrophage mRNA induced OxLDL binding activity on oocytes. An excess of
      acetylated LDL (AcLDL) inhibited the binding of OxLDL by only 30%, indicating the
      expression of OxLDL receptors distinct from the scavenger receptor (SRA). The
      library was screened and analyzed by competition binding using [125I]OxLDL and
      AcLDL, to avoid cloning of SRA. One of the purified clones encoded a peptide with
      85% identity with human acyl-coenzyme A:cholesterol acyltransferase (ACAT).
      Injection of ACAT mRNA into oocytes induced specific binding of OxLDL. ACAT is
      expressed in mouse macrophages as a approximately 3.6 kB transcript and the
      expression is upregulated in human THP-1 cells treated with PMA.

PMID- 8579616
TI  - Anti-sense oligodeoxynucleoside phosphorothioates nonspecifically inhibit
      invasion of red blood cells by malaria parasites.
AB  - Anti-sense and sense oligodeoxynucleoside phosphorothioates, based on analysis of
      the secondary structure of Plasmodium falciparumdihydrofolate reductase
      thymidylate synthase mRNA, were synthesized. Their effects on P. falciparum
      growth in vitro were examined by microscopy and [3H] hypoxanthine incorporation.
      Both anti-sense and sense oligodeoxynucleoside phosphorothioates inhibit invasion
      of red blood cells by merozoites and this is interpreted as being caused by their
      polyanionic nature. Specific anti-sense effects of the oligonucleoside
      phosphorothioates could not however be demonstrated.

PMID- 8579617
TI  - G-protein and tyrosine kinase receptor cross-talk in rat aortic smooth muscle
      cells: thrombin- and angiotensin II-induced tyrosine phosphorylation of insulin
      receptor substrate-1 and insulin-like growth factor 1 receptor.
AB  - Insulin-like growth factor I is an autocrine/paracrine factor for vascular smooth
      muscle cells and is required for angiotensin II- and thrombin-induced
      mitogenesis. The insulin-like growth factor I-triggered signaling pathway
      involves autophosphorylation of the beta-subunit of its tyrosine kinase receptor
      and phosphorylation of insulin receptor substrate-1, the latter providing binding
      sites for proteins with src homology-2 domains. In rat aortic smooth muscle cells
      we observed that both angiotensin II and thrombin induced rapid tyrosine
      phosphorylation of insulin receptor substrate-1. Our results also demonstrated
      that these mitogens rapidly stimulated phosphorylation of the insulin-like growth
      factor 1 receptor beta-chain. These data demonstrate a novel interaction between
      the G-protein coupled angiotensin II and thrombin receptors and the tyrosine
      kinase insulin-like growth factor I receptor.

PMID- 8579618
TI  - Platelet microparticles: a carrier of platelet-activating factor?
AB  - Platelet-activating factor (PAF) has been considered to be released in a soluble
      form from activated platelets. Also a considerable number of microparticles were
      released from stimulated platelets. To evaluate the possibility that
      microparticles contain PAF, the amount of PAF in whole activated platelets,
      microparticles and the suspending medium was determined by means of bioassay. The
      total amount of PAF released from 3 x 10(8) platelets activated with thrombin
      (0.5 U/ml) plus collagen (10 micrograms/ml) for 10 minutes was 4.6 +/- 1.5 x 10(
      12) mol (n = 8, mean +/- S.D.). Eighty-seven percent of the PAF released from
      platelets was associated with microparticles. PAF released in microparticles is
      susceptible to plasma acetylhydrolase and may be localized on the outer surface
      of microparticles. This is the first report implicating the role of
      microparticles as a novel carrier of mediators formed in the cells.

PMID- 8579619
TI  - Release of superoxide radicals by mouse macrophages stimulated by oxidative
      modification of glycated low density lipoproteins.
AB  - Diabetic patients have high levels of glycated LDL. Although glycated LDLs are
      implicated in the development of atherosclerosis in such patients, convincing
      data are lacking. We observed release of superoxide radicals (O2-) from mouse
      resident peritoneal macrophages stimulated by an oxidized/glycated LDL by using a
      highly sensitive and specific chemiluminescence method. Oxidized/glycated LDL was
      achieved by an addition of low concentration of Fe3+ to glycated LDL. Macrophages
      took up an appreciable amount of the glycated LDL oxidized by iron, leading to
      the development of foam cells, while they did not take up untreated glycated LDL
      or the native LDL. These observations clearly indicate that the oxidized/glycated
      LDL reacts well with macrophages. Since an oxidation of glycated LDL may occur in
      vivo, the oxidized/glycated LDL might play an important role in atherogenesis.

PMID- 8579620
TI  - Does the presence of the 3500 mutant apolipoprotein B-100 in low density
      lipoprotein particles affect their atherogenicity?
AB  - Apolipoprotein B-100 (apo B-100) is the protein component of low density
      lipoprotein (LDL) responsible for its binding and clearance by LDL receptors (LDL
      R). In familial defective apo B-100 (FDB), a mutation in apo B-100 at residue
      3500 markedly reduces its affinity for LDL-R, often causing accumulation of
      defective LDL particles, and an increased proneness to coronary artery disease
      (CAD). In FDB heterozygotes, about 70% of the LDL particles are mutant, which may
      alter their atherogenicity relative to LDL containing normal apo B. Therefore, we
      compared CAD in heterozygous FDB with CAD in heterozygous familial
      hypercholesterolemia (FH), since raised LDL is usually present from birth in both
      conditions, and in FH the LDL particles that accumulate have normal apo B, as the
      inherited defect involves the LDL-R. The clinical presentation of coronary
      atherosclerosis and its angiographic appearance were examined in FDB and FH
      patients matched for conventional cardiac risk factors (hypertension, smoking,
      sex) and serum lipid levels. There was no significant difference between the FDB
      and FH patients (n=11 pairs) in the type of cardiac symptoms or their ages of
      onset (50 +/- 9 vs. 45 +/- 11 years). Coronary angiographic appearance was also
      similar in both groups (n=9 pairs). These observations suggest that LDL particles
      with the 3500 mutation in apo B have the same atherogenicity as LDL particles
      with normal apo B.

PMID- 8579621
TI  - Abnormal cholesterol distribution among lipoprotein fractions in normolipidemic
      patients with mild NIDDM.
AB  - This study was carried out to identify and define lipoprotein abnormalities in
      patients with noninsulin-dependent diabetes mellitus (NIDDM) who do not have
      clinical elevations of cholesterol or triglycerides. Thirty-four male patients
      with mild NIDDM and normolipidemia (plasma cholesterol < or = 240 mg/dl and
      triglycerides < or = 250 mg/dl) were compared with 35 healthy male normolipidemic
      subjects. The two groups had similar age and body mass index. Measurements in the
      two groups included concentrations and chemical composition of lipoproteins and
      sizing of low-density lipoprotein (LDL) particles. The patients with NIDDM,
      compared to control subjects, had two distinct lipoprotein abnormalities: first a
      significantly reduced level of high-density lipoprotein (HDL) cholesterol (mean
      +/- S.D., 35 +/- 8 mg/dl vs. 41 +/-10 mg/dl, respectively; P = 0.006), and
      second, a high cholesterol-to-apolipoprotein (apo) B ratio both in a very low
      density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) fraction
      (mean +/- S.D.; 3.2 +/- 0.8 vs. 2.8 +/- 0.9, respectively; P = 0.02) and in LDL
      fraction (mean +/- S.D.; 1.61 +/- 0.11 vs. 1.52 +/- 0.13, respectively; P =
      0.003). Increased cholesterol content in LDL was mainly due to free cholesterol.
      No differences were detected between the two groups in the frequency of LDL
      pattern A (major LDL peak > 255 A) and pattern B (major LDL peak < or = 255 A).
      However, a higher frequency of LDL pattern B was found in NIDDM patients with low
      plasma total triglyceride concentrations ( < 150 mg/dl) compared to the to the
      control subjects (45% vs. 7%, P = 0.02). Thus in normolipidemic patients with
      mild NIDDM, the major lipoprotein abnormalities were a low level of HDL
      cholesterol and compositional changes in LDL and VLDL + IDL fractions.
      Compositional abnormalities included enrichment of apo B-containing lipoproteins
      with cholesterol. These lipoprotein abnormalities could have atherogenic
      potential in patients with mild NIDDM and normolipidemia.

PMID- 8579622
TI  - Multiple coronary heart disease risk factors are associated with menopause and
      influenced by substitutive hormonal therapy in a cohort of French women.
AB  - The relationship between menopause and cardiovascular risk factors of progestin
      alone or in combination with estrogen were analysed in a sample of French women.
      Three thousand four hundred and forty consecutive women, between 45 and 65 years
      of age, who received a systematic check-up between January 1991 and April 1993
      were enrolled in this study. All biological measurements were performed at a
      central laboratory. Women were classified as premenopausal (n = 1233),
      postmenopausal (n = 1774) if they had not menstruated in the 12 months before
      examination, and perimenopausal (n = 433) if they met at least two of the
      following criteria: elevated levels of serum follicle-stimulating hormone (FSH),
      irregular menses, amenorrhea for less than 12 months, hot flushes. The effect of
      menopause on cardiovascular risk factors was determined in 2167 women between 45
      and 65 years of age (premenopausal n = 790, postmenopausal n = 1377), none of
      whom were presently treated with hormonal replacement therapy (HRT). In addition,
      the effect of progestin was assessed in a group or 397 perimenopausal women, and
      the effect of combined estrogen and progestin replacement therapy in another
      group of 1746 postmenopausal women. Menopause was associated with higher levels
      of serum cholesterol (6.4 vs. 5.9 mmol/l), triglycerides (1.2 vs. 1.0 mmol/l),
      apolipoprotein (apo) B (1.3 vs. 1.1 g/l), apo A-I (1.9 vs. 1.8 g/l), as well as
      with elevated diastolic blood pressure (79.7 vs. 77.0 mmHg). Multivariate
      analysis indicated that these effects were independent of age, body mass index
      (BMI), glycemia, smoking, alcohol intake, exercise and parity. Perimenopausal
      women treated with progestin alone (n = 95) were compared to perimenopausal women
      not using HRT (n = 302). There were no statistically significant differences in
      the levels of cholesterol, triglycerides, apo B, apo A-I, glycemia and blood
      pressure between the two groups. Postmenopausal women using a combination of
      estrogen and progestin (n = 369) had significantly lower levels of serum
      cholesterol (6.1 vs 6.4 mmol/l), triglycerides (1.0 vs. 1.2 mmol/l), apo B (1.2
      vs. 1.3 g/l), systolic (131.9 vs. 137.9 mmHg) and diastolic (76.9 vs. 79.7 mmHg)
      blood pressure than postmenopausal women without hormonal therapy (n = 1377),
      taking into account confounding variables. In contrast, serum apo A-I levels were
      not altered by the combined hormonal therapy. We conclude that menopause is
      associated with the aggravation of multiple cardiovascular risk factors. These
      deleterious factors are affected by a treatment of combining estrogen and
      progestin.

PMID- 8579623
TI  - Non-enzymatic glycation of lipoprotein(a) in vitro and in vivo.
AB  - Nonenzymatic glycation of lipoprotein may contribute to the premature
      atherogenesis of patients with diabetes mellitus by diverting lipoprotein
      catabolism from non-atherogenic to atherogenic pathways. It has been demonstrated
      that the proportion of apolipoprotein B-100 (apo B-100) in glycated form is
      significantly higher in diabetic patients than in non-diabetic controls, and
      equally that plasma lipoprotein(a) Lp(a) levels may be increased in diabetic
      patients. Consequently, we have evaluated the glycation of Lp(a) in vitro and in
      vivo, by use of a combination of m-aminophenylboronate affinity chromatography
      and enzyme-linked immunosorbent assay (ELISA) for apo B-100 and Lp(a). In vitro
      studies were performed on normolipodemic plasma samples containing elevated
      concentrations of Lp(a). These studies establish that Lp(a) can be glycated in
      vitro in the presence of high concentrations of glucose, although to a lesser
      extent than low density lipoprotein (LDL) (15.8% +/- 4.4% and 30.2% +/- 5.4% (P =
      0.0001) after a 48 h incubation at 37 degrees C, respectively). We have also
      shown that apo B-100 was more glycated than apo(a) in the Lp(a) particle. In vivo
      studies have shown that the percentage of glycated Lp(a) in diabetic patients was
      significantly higher than in the control population (2.8% +/- 1.07% versus 2.0%
      +/- 0.43%, P = 0.017). The level of glycated Lp(a) is also positively correlated
      with that of HbA1c in diabetic patients (r=0.6, P=0.002). Since our results show
      that Lp(a) is less susceptible to glycation than LDL, we speculate that glycation
      of LDL may be more relevant to the cardiovascular risk associated with this
      particle than with Lp(a).

PMID- 8579624
TI  - TMP-153, a novel ACAT inhibitor, lowers plasma cholesterol through its hepatic
      action in golden hamsters.
AB  - The mechanism of the hypocholesterolemic action of N-[4-(2-chlorophenyl)-6,7
      dimethyl-3-quinolyl]-N'-(2, 4-difluorophenyl) urea (TMP-153), a potent acyl
      CoA:cholesterol acyltransferase (ACAT) inhibitor, was studies in Golden hamsters.
      TMP-153 (0.5-1.5 mg/kg) dose-dependently reduced plasma total- and low density
      lipoprotein (LDL)-cholesterol without affecting high density lipoprotein (HDL)
      cholesterol. TMP-153 markedly reduced the cholesterol influx into the plasma upon
      intravenous injection of Triton WR-1339. The compound also decreased cholesterol
      absorption calculated from dietary intake, biliary secretion and the absorption
      co-efficient. Hepatic cholesterol secretion was calculated by substracting the
      cholesterol absorption from the cholesterol influx. In hamsters, the liver
      accounted for 92% of the cholesterol influx with the remaining 8% coming from the
      intestine, and both were markedly decreased by TMP-153. Thus, it is likely that
      TMP-153 lowers plasma cholesterol through its hepatic action. In the liver, the
      compound significantly reduced the unesterified cholesterol content in addition
      to markedly reducing the content of esterified cholesterol. In accordance with
      this reduction, the half-life time of [125I]-LDL was significantly shortened by
      the compound, suggesting an increase in LDL receptors. However, the hepatic
      cholesterogenesis from [14C]acetate was decreased by TMP-153 treatment. This
      effect seems to be secondary, since the compound did not inhibit
      cholesterogenesis from [14C]acetate in HepG2 cells. From the data described
      above, the contribution of hepatic secretion and intestinal absorption of
      cholesterol to the plasma cholesterol level in Golden hamsters are discussed.

PMID- 8579625
TI  - Do elevated levels of abdominal visceral adipose tissue contribute to age-related
      differences in plasma lipoprotein concentrations in men?
AB  - Age-related differences in body fat and more specifically in the accumulation of
      abdominal visceral adipose tissue were examined as a potential covariate for the
      alteration in the plasma lipoprotein profile found with aging. For that purpose,
      results from 79 young adults (aged 24.5 +/- 4.0 years) were compared to 61 middle
      aged men (54.7 +/- 6.4 years). Younger men had significantly lower body fat mass
      and abdominal visceral adipose tissue area measured by computed tomography than
      middle-aged men (P < 0.0001). Plasma cholesterol, triglyceride, apolipoprotein
      (apo) B, low density lipoprotein (LDL)-cholesterol and LDL apo B levels, as well
      as the ratio of plasma cholesterol to high density lipoprotein (HDL)-cholesterol
      were all significantly lower in younger men as compared to middle-aged men (P <
      0.0001). The comparison of younger men to middle-aged men with comparable levels
      of abdominal visceral fat and total body fat eliminated the age-related
      differences in plasma triglyceride and in the ratio of plasma cholesterol to HDL
      cholesterol, whereas the difference in plasma apolipoprotein B levels, although
      still significant, was largely reduced. Age-related differences in plasma
      cholesterol and in LDL-cholesterol levels were still observed after this matching
      procedure and the differences between age-groups were essentially of similar
      magnitude than before pairing. In summary, these results suggest that the
      deterioration of plasma lipoprotein profile observed in middle-aged men as
      compared to young adult men is partly mediated by concomitant increases in total
      body fat and abdominal visceral adipose tissue. However, other factors related to
      the aging process appear to be involved, particularly for the age-related
      increase in plasma LDL-cholesterol.

PMID- 8579626
TI  - Variability in cholesterol content in serum and aortic tissue in apolipoprotein E
      deficient mice is comparable in inbred (129/Sv) and outbred (mixed 129/Sv and
      C57BL/6) mice.

PMID- 8579627
TI  - Evidence of lipid oxidation in pulmonary artery atherosclerosis.

PMID- 8579628
TI  - Apo B signal peptide insertion/deletion polymorphism is involved in postprandial
      lipoparticles' responses.
AB  - The changes in postprandial concentrations of five lipoparticles (LpC-III, LpC
      III:B, LpC-IIInoB, LpA-I and LpA-I:A-II) were studied on 144 apparently healthy
      (71 male and 73 female) subjects during the 4 h following the ingestion of a
      1.260 kJ milkshake. The influence of apo B signal peptide polymorphisms, apo E
      polymorphism, and other factors including age, gender, BMI, tobacco and alcohol
      consumption on the postprandial responses of lipoparticles was investigated. Apo
      A-I-containing lipoparticles were not influenced during the 4 h following the
      test meal except for LpA-I:A-II, which decreased in women. LpA-I:A-II is the only
      particle that showed a gender-dependent change in postprandial concentration. Apo
      CIII-containing lipoparticles showed significant postprandial variations.
      Particles containing both apo B and apo C-III (total LpC-III and LpC-III:B),
      mainly present in VLDL fraction, had significantly different postprandial
      responses among the genotypes of the apo B signal peptide polymorphism.
      Homozygotes for Del allele showed a decrease of LpC-III:B concentrations over the
      4 h, whereas Ins/Ins homozygotes and Ins/Del heterozygotes had a peak in
      concentration at 2 h. The apo B signal peptide polymorphism explained 2.3% of the
      variance of LpCIII:B, whereas apo E polymorphism did not influence the
      postprandial concentrations of any lipoparticles.

PMID- 8579629
TI  - Relationships between insulin metabolism, serum lipid profile, body fat
      distribution and blood pressure in healthy men.
AB  - Insulin resistance and hyperinsulinaemia may be important in a cluster of
      coronary heart disease-related metabolic disturbances known as the insulin
      resistance syndrome. Whether the relationships between insulin and other features
      of the syndrome are independent of the amount and distribution of body fat is
      uncertain. We have investigated these relationships in 103 healthy males, using
      dual-energy X-ray absorptiometry to measure body fat directly. Volunteers
      underwent an intravenous glucose tolerance test (IVGTT), from which insulin
      sensitivity, secretion and elimination were determined by mathematical modelling
      analysis. Independently of adiposity and body fat distribution, serum
      triglyceride concentration was correlated with fasting C-peptide concentration
      and second-phase intravenous glucose tolerance test insulin concentration (r =
      0.42, P < 0.001; r = 0.28, P < 0.05). High density lipoprotein subfraction 2
      (HDL2) cholesterol was correlated with fasting C-peptide, first-phase IVGTT
      insulin concentration, and the hepatic insulin throughout index (r = -0.15 -0.20,
      -0. 20 respectively, all P < 0.05). The association of HDL2 cholesterol with the
      hepatic throughput index was additionally independent of serum triglyceride
      concentration (r = -0.18, P < 0.05). Our results suggest that relative
      hyperinsulinaemia leads to elevated triglyceride concentration, independently of
      body fat mass and distribution. Furthermore, the independent association of HDL2
      cholesterol with hepatic insulin throughput confirms that hepatic insulin
      processing may may directly influence lipoprotein metabolism.

PMID- 8579630
TI  - Lipid peroxidation of circulating low density lipoproteins with age, smoking and
      in peripheral vascular disease.
AB  - In this study, lipid peroxides in plasma and the low density lipoprotein (LDL)
      fraction and plasma concentrations of vitamin E, lipids and lipoproteins were
      measured in 22 smokers (mean age 35 years), 26 non-smoking patients with
      peripheral vascular disease (PVD), mean age 66 years), and 23 younger (ages < or
      = 55 years) and 26 older (ages > 55 years) healthy subjects. Plasma lipid
      peroxide concentrations in the PVD patients (105.9 +/- 20.6 vs. 91.8 +/- 15.8 ng
      malondialdehyde (MDA)/ml plasma, mean +/- S.D.) and the smokers (94.1 +/- vs.
      74.0 +/- 13.9 ng MDA/ml plasma) were significantly elevated compared with levels
      in the appropriate control subjects and levels were significantly higher in older
      compared with younger control subjects. Plasma LDL lipid peroxides were also
      significantly raised in patients with PVD and smokers compared with control
      values (PVD): 37.1 +/- 7.7 vs. 26.3 +/- 4.1 ng MDA/ml plasma; smokers: 30.4 +/-
      6.9 vs 24.9 +/- 7.5 ng MDA/ml plasma). The ratio of LDL lipid peroxides: LDL
      cholesterol was significantly higher in the smokers, and plasma cholesterol and
      LDL-cholesterol were significantly higher in patients with PVD compared with
      other groups of subjects. The ratio of vitamin E: total lipid was not
      significantly different between the study groups. These data show that lipid
      peroxide levels in the plasma LDL fraction are elevated along with raised
      circulating levels in patients with PVD and smokers but that LDL lipid peroxide
      concentrations were independent of age in the healthy subjects. Elevated LDL
      lipid peroxide concentrations may may be mainly due to abnormally high LDL levels
      in PVD patients, whereas in smokers, the concentration of lipid peroxides in the
      LDL particles is raised and might render the lipoprotein more atherogenic.

PMID- 8579631
TI  - Inhibitory effect of a single local probucol administration on neointimal
      formation in balloon-injured rat carotid artery.
AB  - The aim of this study was to determine whether a single local probucol
      administration could suppress neointimal formation in balloon-injured rat carotid
      artery. Rats were divided into four groups; (i) rats receiving no probucol
      (control group); (ii) rats receiving topical application of 50 mg probucol at the
      time of ballooning (p-top group); (iii) rats fed chow containing 1% probucol (p
      fed group; (iv) rats receiving both topical application of 50 mg probucol and
      chow containing 1% probucol (p-top/fed group). Although serum total cholesterol
      levels did not significantly differ between the control and the p-top groups at
      two weeks after balloon injury, the p-top group had a smaller intimal/medial
      ratio or intimal area than the control group (0.97 +/- 0.11 vs. 0.53 +/- 0.08 or
      0.15 +/- 0.02 mm2 vs. 0.08 +/- 0.02 mm2 respectively, P < 0.01). Neointimal
      formation was suppressed to a similar extent in the p-fed group, in which serum
      total cholesterol level was approximately 40% lower than that in the control
      group. Thus, a single local delivery of probucol can suppress neointimal
      formation in balloon-injured rat carotid artery without altering serum lipid
      level.

PMID- 8579633
TI  - Toxicity of oxysterols to human monocyte-macrophages.
AB  - We have investigated the toxicity of the cholesterol oxidation products
      (oxysterols), 7 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol, 7
      ketocholesterol, 25-hydroxycholesterol and 26-hydroxycholesterol to human
      monocyte-macrophages in vitro. The 7-position derivatives are present in low
      density lipoprotein (LDL) oxidised with copper (II) sulphate and macrophages, and
      in extracts of human atherosclerotic lesions, which also contain 26
      hydroxycholesterol. We have also assessed 25-hydroxycholesterol for toxicity
      because it has often been used in studies of 3-hydroxy-3-methyl-glutaryl-CoA (HMG
      CoA) reductase inhibition and LDL receptor down-regulation. Measurement of
      radioactivity release from monocyte-macrophages preloaded with tritiated adenine,
      as a means of assessing cytotoxicity that all the oxysterols showed time- and
      concentration-dependent toxicity. The cytotoxic potency of 26-hydroxycholesterol
      was the greatest. The 7-position derivatives also produced marked cell damage,
      though at higher concentrations than for 26-hydroxycholesterol. Of the oxysterols
      assessed, the toxicity of 25-hydroxycholesterol was the least. The cytotoxicity
      of 7 beta-hydroxycholesterol and 26-hydroxycholesterol was also shown using the 3
      [4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) dye reduction
      assay which confirmed that 26-hydroxycholesterol was more toxic than 7 beta
      hydroxycholesterol. Incubation of monocyte-macrophages with cholesterol added to
      the different oxysterols gave varying results. Cholesterol, which was not itself
      toxic, inhibited the toxicity of 25-hydroxycholesterol and 26-hydroxycholesterol,
      but the toxicity of the 7-position derivatives was not affected. The possible
      relevance of these molecules to the death of macrophages seen in atherosclerosis
      is discussed.

PMID- 8579632
TI  - Insulin-like growth factor binding protein-1 inhibits arterial smooth muscle cell
      proliferation in vitro but does not reduce the neointimal response to balloon
      catheter injury.
AB  - The biological effects of the insulin-like growth factors (IGFs) are modulated by
      circulating binding proteins (BPs), including IGFBP-1. We have investigated the
      effects of recombinant IGFBP-1 on smooth muscle cell (SMC) proliferation in vitro
      using cultured rat aortic SMCs and in vivo using the ballooned rat carotid artery
      model. IGFBP-1 inhibited IGF-1 induced and spontaneous SMC proliferation dose
      dependently. In vivo, the effective half-life of IGFBP-1 was approximately 5 h
      when administered by intraperitoneal injection. High peri-operative plasma levels
      of IGFBP-1 (mean 1780 ng/ml) were attained by giving and intravenous dose
      immediately prior to balloon injury in 9 rats. Animals injected with human serum
      albumin or saline were used as controls. In vivo cell proliferation was assessed
      by BrdU pulse labeling each animal prior to the termination of the experiment, 6
      days after balloon injury. Absolute intimal thickness, intima-media ratio and
      cell proliferation indices were measured for each animal. Although IGFBP-1
      inhibited SMC proliferation in vitro, high plasma concentrations of IGFBP-1 did
      not reduce neointimal size or cell proliferation. IGFBP-1 administration was,
      however, associated with a significantly greater loss of body weight (P < 0.05),
      indicating that the peptide had a profound metabolic effect. Our data suggest
      that IGF-1 does not have a major role in inducing SMC proliferation in the early
      phases following angioplasty.

PMID- 8579634
TI  - Expression of growth factor receptors in arterial smooth muscle cells. Dependency
      on cell phenotype and serum factors.
AB  - The effects of modulation of rabbit aortic smooth muscle cells (SMCs) from the
      'contractile' phenotype on surface membrane receptors binding epidermal growth
      factor (EGF), basic fibroblast growth factor (bFGF) and platelet-derived growth
      factor-BB (PDGF-BB), as well as their responsiveness to these growth factors was
      investigated in cell culture. Cells predominantly of the 'contractile' phenotype
      expressed low numbers of high affinity EGF and bFGF receptors (EGFr: 1.09 +/-
      0.18 fmol/10(6) cells; bFGFr: 0.32 +/- 0.07 fmol/10(6) cells). Upon modulation
      from the 'contractile' phenotype, the expression of these cell surface receptors
      increased greatly: 8- and 11-fold with respect to EGF and bFGF receptors. Cell
      surface receptors binding [125I]-PDGF-BB were largely unaltered. The elevated
      bFGF receptor number appeared dependent on SMC modulation from the 'contractile'
      phenotype and serum; the latter factor did not influence EGF receptor numbers. In
      both instances the increase in receptor numbers was independent of the
      proliferation status of the cells. Cells expressing high levels of the growth
      factor receptors also rapidly entered the cell cycle, proliferated, and exhibited
      growth factor-specific changes in shape in the presence of these growth factors.
      Because the effects on growth factor receptor numbers were observed in confluent
      cells, such alterations, are likely to play a significant role in vessel
      remodelling following balloon catheter angioplasty, in atherosclerotic vessels
      and the vascular hypertrophy associated with hypertension.

PMID- 8579635
TI  - Ultrastructural studies on macromolecular permeability in relation to endothelial
      cell turnover.
AB  - Our previous light microscopic studies demonstrated the correlation of focal
      arterial uptake of macromolecules with the mitosis or death of endothelial cells
      (ECs). To investigate horseradish peroxidase (HRP) permeability associated with
      the clefts surrounding these ECs at the ultrastructural level, experiments were
      performed on rat thoracic aortae by using transmission electron microscopy. In en
      face preparations of aortic specimens, light microscopy was used first to detect
      mitotic ECs by hematoxylin staining prior to electron microscopy. Dying (or dead)
      ECs containing cytoplasmic immunoglobulin G (IgG) were identified by an indirect
      immunogold technique, HRP was found to permeate from the vessel lumen through the
      widened junctions around the mitotic and dying cells, as well as some non-widened
      junctions and the plasma membrane of dying cells. The transiently open junctions
      during cell turnover lead to an increased transendothelial permeability to
      macromolecules. In addition to its enhanced passage through the leaky junctions
      around EC turnover and through the damaged membrane of dying cells. HRP can also
      traverse many normal intercellular clefts into the subendothelial space of the
      aorta. These observations show that normal intercellular junctions can provide a
      significant pathway for the transport of macromolecules with the size of HRP, and
      that HRP transport is enhanced in transiently open junctions surrounding ECs
      undergoing turnover. The widened junctions around the mitotic and dying cells
      provide the pathway for macromolecules larger than HRP, e.g., the low density
      lipoproteins (LDLs).

PMID- 8579636
TI  - Calcified deposit formation in intimal thickenings of the human aorta.
AB  - The formation of calcified deposits in intimal thickenings of human aorta was
      studied by electron microscopy. Microzones of calcification were detected in
      about 20% of fatty streaks and were located predominantly in the deep
      musculoelastic layer of the intima. Calcified deposits formed only on previously
      existing structures including extracellular vesicles and unesterified
      cholesterol. Calcified deposits in the musculoelastic layer of the intima
      localised inside altered elastin fibres, but initiating the calcification of of
      elastin required the prior accumulation of cholesterol esters inside elastin
      fibres. Co-localization of calcified deposits and elastin fibres was followed by
      destruction of elastin. The present study suggests that at an early stage of
      development is atherosclerotic lesions, calcified deposits are formed by a
      physicochemical process which is not strongly controlled by the intimal cells.
      The recognition of calcified deposits in intimal thickenings support the
      hypothesis that a subset of fatty streaks might progress to fibrous plaques in
      human atherosclerosis.

PMID- 8579637
TI  - Protein catabolic rate determination from a single measurement of dialyzed urea.
AB  - Protein catabolic rate (PCR, in g protein/kg/day) for anuric patients can be
      accurately determined without blood sampling by equating urea generation over 7
      days to the urea dialyzed in the three dialyses of this period as measured by
      partial dialysate collection (PDC) or with a urea monitor. The feasibility of
      determining the week's dialyzed urea from measurement of urea dialyzed in a
      single session, obviating the need to monitor three consecutive dialyses, was
      examined in a steady-state simulation of 540 anuric patients spanning the full
      range of dialysis parameters. It was found that the first, midweek, and last
      dialyses account for nearly constant fractions (37.9, 32.1, and 30.0%,
      respectively) of the week's urea removal, leading to equations of the form: PCR =
      CU/BW + 0.17 where U is the grams of urea dialyzed in the first, midweek, or
      final dialysis of the week, C = 2.45, 2.89, or 3.10, respectively, and BW is the
      patient's dry weight in kilograms. These equations were tested on 1312 weeks of
      PDC data gathered in 42 dialysis patients. Using the midweek U resulted in a mean
      absolute error in PCR < 0.05 g/kg/day when compared to PCR determined using all
      three of the week's U values.

PMID- 8579638
TI  - Inhibition of tumor necrosis factor production and ICAM-1 expression by
      pentoxifylline: beneficial effects in sepsis syndrome.
AB  - Tumor necrosis factor (TNF) has a pivotal role in the pathogenesis of sepsis and
      septic shock. Suppression of its biosynthesis might therefore be one of the
      strategies in the treatment of sepsis. When peripheral white blood cells were
      stimulated with either E. coli lipopolysaccharide (LPS) or Staphylococcus aureus,
      pentoxifiline (PTX) inhibited TNF production. In contrast, only a moderate
      inhibitory effect was observed on the induction of interleukin 6 (IL-6). PTX
      inhibited not only the TNF production of monocytes, but also the TNF secretion of
      both granulocytes and unseparated whole blood. The in vitro TNF and IL-6
      producing capacities were higher in septic patients (n = 31) than in healthy
      blood donors (n = 15). Administration of PTX (400 mg/day) to 20 of the septic
      patients resulted in TNF production similar to that found in healthy controls. It
      also subsequently led to an improvement of the clinical status classified by the
      APACHE II score. The soluble intercellular adhesion molecule-1 (sICAM-1) level
      was significantly higher in the sera of septic patients before PTX treatment (800
      1200 ng/ml) than in normal individuals (50-150 ng/ml), but it decreased following
      PTX therapy. Cytofluorometric analysis revealed that the expression of ICAM-1 on
      stimulated mononuclear cells was inhibited by PTX. It is presumed that the
      suppressive effect of pentoxifylline on TNF production may be of clinical
      importance, improving the therapeutic strategies in septic syndrome.

PMID- 8579639
TI  - Effect of ursodeoxycholic acid on biochemical parameters, hepatocyte
      proliferation and liver histology in galactosamine hepatitis in the rat.
AB  - The effect of oral administration of ursodeoxycholic acid (UDCA) on biochemical
      parameters, liver histology and liver cell proliferation was investigated in rats
      with galactosamine hepatitis. Treatment with UDCA led to a decrease of
      aminotransferases, but did not show any significant changes in liver histology or
      liver cell proliferation. The improvement of liver enzymes without change of
      histology in this animal model of hepatitis following treatment with UDCA is in
      agreement with results obtained from clinical trials with UDCA in patients with
      chronic viral hepatitis.

PMID- 8579640
TI  - Somatostatin reduces the levels of tumor necrosis factor alpha in a rat model of
      endotoxemia induced by lipopolysaccharide.
AB  - The role of tumor necrosis factor alpha (TNF) in the toxic and lethal effects of
      the endotoxemia associated with septic shock is well known. This study was
      designed to establish whether natural somatostatin (SS-14) is capable of
      modifying the production of TNF in a model of septic shock induced in the rat by
      bacterial lipopolysaccharide (LPS), and its theoretical relationship to
      prostaglandin E2 (PGE2). An experimental study was carried out in 80 Wistar rats
      subjected to intravenous LPS injection. Perfusion of SS-14 at 2 micrograms/h or
      continuous isotonic saline (IS) at 0.1 ml/h started 30 min prior to LPS injection
      and continued until 90 min after. All the animals were primed 15 days earlier
      with on intraperitoneal dose of BCG (2.2 x 10(7) CFU). ELISA assays were used to
      measure TNF levels after 90 min of perfusion and those of PGE2 at 30 and 90 min.
      The effects of two different doses of LPS (0.5 mg/kg of body weight and 5 mg/kg
      bw) were compared. SS-14 administration was associated with a decrease in TNF
      levels (1130.0 +/- 272.4 vs 4720.0 +/- 1278.1 pg/ml, P = 0.013), and an increase
      in serum PGE2 basally (255.7 +/- 94.2 vs 62.0 +/- 10.6 pg/ml, P = 0.04) and after
      90 min of perfusion (1872.7 +/- 1250.6 vs 1009.7 +/- 612.0 pg/ml, P = NS), there
      being a statistically significant correlation between the basal PGE2 levels and
      these TNF after 90 min when compared using a regression model (r = -0.88, P =
      0.04 for the 0.5 mg/kg dose; r = -0.47, P = 0.07 for 5 mg/kg). At 90 min, the
      level of TNF also depended on the PGE2 values (r = 0.84, P = 0.07 for 0.5 mg/kg;
      r = 0.55, P = 0.03 for 5 mg/kg). Multiple regression permitted TNF levels to be
      estimated on the basis of basal and 90 min PGE2 levels (P = 0.03). Pretreatment
      with SS-14 led to a significant reduction of TNF and an increase of PGE2, there
      being an apparent correlation between the two.

PMID- 8579641
TI  - [Ca2+]i in human heart failure: a review and discussion of current areas of
      controversy.
AB  - Multiple abnormalities have been reported in the setting of human heart failure.
      It is unclear whether detected changes reflect adaptive alterations in myocardium
      subjected to increased and sustained hemodynamic overload or are pathogenic to
      the disease process. As a result of the observation that the primary defect in
      heart failure is decreased pump function, investigators have concentrated their
      efforts on determining systolic [Ca2+]i as a logical corollary and a causative
      mechanism for contractile dysfunction. A simple cause and effect relationship has
      therefore been proposed with regard to contractile dysfunction and [Ca2+]i. Yet
      some investigators have found no difference in peak systolic [Ca2+]i between
      failing and non-failing human myocardium, whereas others have found peak [Ca2+]i
      to be significantly reduced in failing hearts. Resting calcium concentrations
      have been reported either to be elevated in failing human myocardium or not
      different from non-failing human myocardium. Investigators should now appreciate
      that the force-calcium relationship is not a simple relationship. One must take
      into account the prolonged time course and slowed mobilization of [Ca2+]i as
      opposed to simply peak [Ca2+]i. When put in perspective of mechanisms and
      determinants of the Ca(2+)-force relationship, we begin to realize that failing
      human myocardium has the "potential" to generate normal levels of force. Only
      when stressed by [Ca2+]i overload and/or frequency perturbation does myocardium
      from patients with end-stage heart disease demonstrate contractile failure.
      Although [Ca2+]i availability and mobilization are likely to play a role in the
      systolic as well as diastolic dysfunction reported in human heart failure, it is
      likely that other mechanisms are involved as well (e.g., myocardial energetics).
      Myocardial energetics is directly related to [Ca2+]i and mobilization in failing
      human myocardium, because metabolites, e.g., ADP, inhibit pumps, such as
      sarcoplasmic reticulum Ca2+ ATPase activity. We therefore conclude that there is
      a role for intracellular calcium mobilization and myocardial energetics for
      systolic and diastolic dysfunction seen in human heart failure.

PMID- 8579642
TI  - Does tranexamic acid decrease bleeding in patients undergoing cardiopulmonary
      bypass?
AB  - We reviewed the records of 66 patients who underwent cardiopulmonary bypass; half
      of these patients received the plasmin inhibitor, tranexamic acid. The
      demographics were not different between the group who received tranexamic acid
      and the group who did not (control group). There was no difference in the heparin
      or protamine requirements between the two groups. There was a significantly
      greater amount of 12-hr chest tube bleeding in the control group (495 +/- 484 vs.
      863 +/- 655 in the control and tranexamic acid groups, respectively; p < .02).
      There was no difference between the groups in either the post-operative
      hematocrit, platelet count or the number of patients requiring transfusion.
      Although tranexamic acid decreased the amount of chest tube output, there was no
      demonstrable patient benefit derived from its use.

PMID- 8579644
TI  - Polyhydramnios-oligohydramnios in a twin pregnancy complicated by fetal
      glomerulocystic kidney disease.
AB  - Polyhydramnios and oligohydramnios in twin gestation is most often caused by twin
      twin transfusion syndrome. Presented is a monozygotic twin pair with
      polyhydramnios and oligohydramnios, in which both twins had glomerulocystic
      kidney disease of differing severity. The more severely affected donor twin died
      of renal failure in the neonatal period. The surviving twin is well following
      unilateral nephrectomy. This case illustrates the varied spectrum of pathology in
      glomerulocystic kidney disease.

PMID- 8579645
TI  - Autologous blood donation with placenta previa: is it feasible?
AB  - Autologous blood donation has been recommended for patients with placenta previa.
      We hypothesized that premature delivery, preexisting anemia, and bleeding would
      limit its utilization. We reviewed the charts of all patients admitted with
      placenta previa between July 1, 1989, and April 30, 1992. To be eligible for
      autologous donation we assumed that the patient would need to be asymptomatic
      with a hematocrit 34% or higher at 32 weeks' gestation. Eighty-eight patients
      were admitted with placenta previa, 12 (14%) of whom were eligible for autologous
      donation. Two eligible patients required transfusion at delivery and four
      delivered prior to 34 weeks. Few patients with placenta previa are eligible for
      autologous donation and although two would have used their autologous units,
      twice as many may have been compromised by recent autologous donation. We
      conclude that autologous donation is not feasible in a majority of patients with
      placenta previa and is of limited usefulness in its management.

PMID- 8579643
TI  - Analysis of Egr-1 protein induction in murine peritoneal macrophages treated with
      granulocyte-macrophage colony-stimulating factor.
AB  - Transcription of early growth response gene-1 (Egr-1) is required for macrophage
      differentiation. Since granulocyte-macrophage colony-stimulating factor (GM-CSF)
      induces macrophage proliferation as well as the transcription of Egr-1 mRNA, we
      characterized the induction of Egr-1 protein in murine peritoneal macrophages
      following treatment with GM-CSF. As determined by Western blot analysis, the
      concentration of GM-CSF required to induce detectable Egr-1 protein in
      macrophages was 50 units/ml, and the inducible Egr-1 protein species was 80 kDa.
      Following stimulation of macrophages with GM-CSF, Egr-1 protein was detected
      within 25 min and reached maximum level at 70 min. The concentration of GM-CSF
      that was required to induce Egr-1 protein in macrophages was similar to that
      required to induce macrophage proliferation. A similar concentration has been
      detected previously in mouse serum exposed to bacterial endotoxin in vivo,
      suggesting that the 80 kDa Egr-1 protein may be induced in macrophages under the
      physiologic circumstances of pathogen invasion. Thus, our data support further
      study on the role of Egr-1 protein in mediating GM-CSF induction of macrophage
      proliferation.

PMID- 8579646
TI  - Comprehensive ultrasound examination in a private perinatal practice.
AB  - A retrospective review of the types of patients seen and the accuracy of the
      diagnosis made was undertaken for patients referred for comprehensive ultrasound
      examination in a large private perinatal practice. A review of the perinatal
      ultrasound database, neonatal intensive care database, and hospital charts was
      done in 1338 patients referred to the perinatal ultrasound laboratory for
      comprehensive ultrasound examination during a 2-year period. Accuracy of the
      ultrasound diagnosis and relationships between structural anomalies seen on
      ultrasound examination and perinatal outcome was undertaken. Positive and
      negative predictive values for the ultrasonic diagnosis were 82% and 98%,
      respectively. There were 19 (1.4%) false-positive diagnoses and 38 (2.8%) false
      negative diagnoses. There was a high correlation between structural anomalies and
      chromosomal anomalies, with 15 of the 87 infants (17.2%) with structural
      anomalies also having chromosomal anomalies. The accuracy of ultrasonic diagnosis
      for comprehensive examinations in a large private perinatal practice compared
      favorably with previous reports in the literature. The information presented in
      this study should be helpful to obstetric centers with similar patient
      populations.

PMID- 8579647
TI  - An index for early assessment of neonatal survival in low birthweight infants.
AB  - Since its development in the 1950s, the Apgar index has come into widespread use
      as a tool to evaluate neonatal condition, with predictive implications for
      mortality and morbidity. However, Apgar scores were validated in predominantly
      term infants and have questionable prognostic value for low birthweight infants.
      The purpose of this study was to develop a survival index applicable to premature
      infants. Thirty-six perinatal variables were evaluated initially, based on data
      from 441 neonates weighing 500 to 1800 g. A multifactorial index of nine
      variables was derived, each independently related to mortality. Sensitivity of
      the index was 95%, specificity was 68%, positive predictive value was 90%, and
      negative predictive value was 81%. This index provides the most accurate tool yet
      reported in the literature for predicting concurrent survival of premature
      infants. The tool is recommended for use as an index of neonatal condition for
      low birthweight infants. Its additional use, as a predictor of the likelihood of
      survival would require time and place specific validation.

PMID- 8579648
TI  - Small for gestational age fetus and neonatal outcome: reevaluation of the
      relationship.
AB  - A retrospective review of 1316 neonates who had been evaluated in the Perinatal
      Laboratory of my institution during the years 1990 and 1991 was undertaken to
      study the relationship between birthweight for gestational age, maternal high
      risk factors, and neonatal ponderal index with neonatal outcome. Patients were
      stratified as to gestational age at delivery and the presence of significant
      congenital abnormalities. Univariant analysis (chi square or t test, where
      appropriate) was done comparing neonatal outcome for neonates that were or were
      not small for gestational age (SGA), whose mother did or did not have high-risk
      factors, and for infants with normal or abnormal ponderal indices. Multivariant
      analysis was also done using logistic regression analysis. In infants without
      congenital anomalies delivering at term only the presence of maternal risk
      factors had prognostic significance, whereas both maternal risk factors and
      defining infants as SGA had prognostic value in infants delivering preterm,
      especially less than 34 weeks' gestation. Ponderal index had no significant
      prognostic value at any gestational age. The data supports the concept that
      intrauterine growth retardation as defined as an SGA, low birthweight for
      gestational age infant, may be an inaccurate classification for infants
      delivering at term, but does have prognostic significance in preterm infants,
      especially those less than 34 weeks' gestational age.

PMID- 8579649
TI  - Further complications in the stuck twin syndrome: decubiti ulcerations and
      iatrogenic exsanguination.

PMID- 8579650
TI  - Mode of delivery following external cephalic version and induction of labor at
      term.
AB  - External cephalic version should be followed by fetal and maternal surveillance
      until delivery. To shorten this period of surveillance, a protocol of version at
      term, followed by immediate induction of labor, was adopted. The aim of the
      present study was to evaluate the effect of this protocol on the subsequent mode
      of delivery. Two hundred and ninety-one singleton breech pregnancies were
      included in this study. Of these, 74 cases underwent version, 75% of which were
      successful. Success of version compared to failed version was associated with
      statistically significant (p < 0.001) lower rate of cesarean sections (9% and
      67%, respectively). The overall rate of abdominal deliveries in the version group
      (74 cases) was statistically significantly lower compared with two other groups:
      one composed of breech pregnancies that did not undergo versions, but would have
      been qualified for it, had they been referred on time (121 cases), and the other
      (96 cases) that did not have versions done because of contraindications to its
      performance (cesarean rates, 23%, 54%, and 79%, respectively; p < 0.001). It may
      be concluded that a policy of external cephalic version at term is effective in
      lowering the incidence of cesarean deliveries, and the added intervention of
      induction of labor does not negate this effect.

PMID- 8579651
TI  - Maternal prepregnant weight and weight gain: relationship to placental
      microstructure and morphometric oxygen diffusion capacity.
AB  - This study examines the effects of maternal prepregnant weight and gestational
      weight gain on the size, microstructure, and function of the human placenta.
      Standard gross, histologic, and histomorphometric techniques were used to examine
      placentas obtained from the deliveries of 77 poor, black 12- to 30-year-old
      subjects in relation to maternal prepregnant weight and the rate of maternal
      weight gain during gestation. The weight, volume, and fetal capillary surface
      area of the placenta increased significantly in relation to both maternal
      prepregnant weight and the rate of maternal weight gain during gestation.
      Prepregnant weight was a more important determinant of placental size and fetal
      capillary surface area than was the rate of maternal weight gain. The rate of
      maternal weight gain was a more important determinant of the density of fetal
      capillary tissues within the placenta and of placental resistance to oxygen
      diffusion than was prepregnant weight. Both maternal prepregnant weight and the
      rate of maternal weight gain during gestation relate positively to the size of
      the placenta, but they have different, potentially complementary effects on
      placental microstructure and function.

PMID- 8579652
TI  - Immunologic evaluation of a neonate born to an immunosuppressed kidney transplant
      recipient.
AB  - There are only a few reports about immunologic evaluation of neonates who have
      been exposed to immunosuppressive drugs during fetal life. We followed up
      immunoglobulins, T, B and natural killer (NK) cell levels in an infant of a
      kidney transplant recipient who has been exposed to cyclosporine, azathioprine,
      and prednisolone during his fetal life. B-cell percentage, absolute counts, and
      immunoglobulin levels were normal at birth, but IgG value was lower than our
      normal controls at 3 months and low normal at 6 months of age. Serum IgM levels
      were normal in all determinations, but IgA levels were lower than the control
      values during the follow-up period. B cell percentage and absolute counts were
      higher than the control values at 3 and 6 months. T-cell subpopulations were
      normal except for CD4+/CD8+ ratios that stayed high normal due to increased CD4+
      cells. CD16+ (NK cells) absolute counts and percentages were below normal at
      birth and at 3 months. Clinically, increased susceptibility to infection was not
      observed during the follow-up period. More immunologic studies are needed on
      possible effects of in utero exposure to cyclosporine, azathioprine, and
      prednisolone.

PMID- 8579653
TI  - Prenatal sonographic diagnosis of Treacher Collins syndrome: a case and review of
      the literature.
AB  - We report the prenatal ultrasonographic diagnosis of a fetus with mandibulofacial
      dysostosis (Treacher Collins syndrome). Sonographic findings included:
      polyhydramnios, microcephaly, abnormal fetal facial features (slanting forehead,
      microphthalmos, micrognathia), and abnormal fetal swallowing. A review of the
      current literature pertaining to prenatal diagnosis of this condition is
      presented.

PMID- 8579654
TI  - Tracheal TDx fetal lung maturity test for assessing lung maturity in newborns
      with respiratory distress.
AB  - We evaluated a modified TDx-fetal lung maturity (FLM) test for estimating
      surfactant in small volume tracheal aspirates in 140 infants requiring mechanical
      ventilation. Respiratory distress syndrome was present in 75 infants, and 68 had
      TDx FLM less than 60 mg/dL (sensitivity, 90.6%). Respiratory distress was absent
      in 65 infants, 56 had TDx FLM more than 60 mg/dL (specificity, 86.1%). The
      modified TDx-FLM assay is highly automated, has a fast turn-around time (less
      than 30 minutes), has high reproducibility, and is less expensive than other
      available methods. This method has potential routine application in the diagnosis
      of surfactant deficiency, and the assessment of surfactant replacement and
      mechanical ventilation therapies.

PMID- 8579655
TI  - Congenital genitourinary tract abnormalities following cocaine exposure in utero.
AB  - The purpose of this study was to review the clinical and ultrasound experience of
      renal tract abnormalities associated with cocaine exposure in utero. We undertook
      a 3-year chart review of all infants admitted to British Columbia's Children's
      Hospital neonatal intensive care unit and Sunny Hill Health Centre for Children
      in order to identify patients with the diagnostic code for maternal drug or
      substance use. There were 136 neonates with a positive history or urine drug
      screen. Renal ultrasound scans had been performed on 79 patients. Ultrasound
      abnormalities were found in 11 patients (14%) and included horseshoe kidney (2),
      unilateral abnormal small kidney (1), duplex kidney (1), and renal tract dilation
      (8). Clinical findings were glandular (2) and juxtaglandular (1) hypospadias with
      chordee. The patients with hypospadias did not have other abnormalities or
      abnormal renal ultrasound scans. In our population of infants exposed to cocaine
      in utero we detected an increased incidence of hypospadias and an increased
      incidence of renal tract abnormalities. We conclude that cocaine exposure in
      utero may well be a risk factor for renal tract anomalies. However, a larger,
      longer-term prospective study is necessary before definitive recommendations can
      be given for routine screening by ultrasound of all infants exposed to cocaine in
      utero.

PMID- 8579656
TI  - Maternal, placental, and neonatal associations with early germinal
      matrix/intraventricular hemorrhage in infants born before 32 weeks' gestation.
AB  - This study tests the hypothesis that histologic placental lesions were
      significantly related to incidence of early or late germinal
      matrix/intraventricular hemorrhage (GM/IVH) in infants of less than 32 weeks'
      gestation independent of maternal or neonatal factors. Maternal and neonatal
      charts of 406 singleton liveborn nonanomalous infants born at less than 32 weeks'
      gestation were studied retrospectively for principal indication for delivery,
      delivery mode, timing of antenatal steroid treatment, diagnosis of labor and
      augmentation, tocolysis, fetal presentation, and umbilical arterial and venous
      blood gas values. Extracted from neonatal charts were gestational age, growth
      measurements, initial hematocrit and white blood cell count, administration of
      surfactant, and in the first 3 days of life, the use of pressor agents and volume
      expansion, lowest blood pressure, and data pertinent to respiratory function.
      Placental histologic examination was reviewed for various lesions, including
      histologic acute inflammation (graded on a scale of 0 to 4). GM/IVH (grades 1 to
      4) diagnosed ultrasonographically less than 72 hours after birth was "early."
      GM/IVH diagnosed after 72 hours of life was defined as "late." Of the 406
      patients, 44 (10.8%) had early GM/IVH; 21 (4.9%) had late GM/IVH. Stepwise
      logistic regression selected five factors independently related to increased
      early GM/IVH risk: Histologic acute inflammation (p < 0.002); gestational age in
      days (p = 0.053); antenatal steroid treatment less than 48 hours before birth (p
      < 0.035); volume expansion in the neonate (p < 0.30), and magnesium sulfate
      tocolysis (p < 0.025). Stepwise regression analysis considering the grade of
      GM/IVH changed the order of variables, with gestational age and use of pressor
      therapy being more strongly related to higher grade of GM/IVH than amnion
      inflammation. Delivery mode, presentation, principal indication for delivery,
      presence/augmentation of labor, mean biophysical profile scores, mean umbilical
      arterial and venous blood gas values, and surfactant therapy were not related to
      early GM/IVH in univariate or multivariate analyses. Neonatal factors associated
      (p < 0.05) with amnion inflammation were volume expansion at delivery and in the
      first 3 days of life, low mean systolic pressure, low mean oxygen pressure, low
      initial hematocrit and cord pH, and increased initial WBC and toxic granulations
      of neutrophils. Only gestational age, and no maternal or placental factors, was
      significantly related to late GM/IVH. Infants who have placentas with acute
      amnion inflammation and receive volume expansion, born to mothers who receive
      less than 48 hour's exposure to antenatal steroids and are selected to receive
      magnesium sulfate tocolysis, have increased incidence of early but not late
      GM/IVH. Amnion inflammation is significantly related to early GM/IVH and with
      early neonatal abnormalities in oxygenation, perfusion, and effective blood
      volume. Intra-amniotic infection leads to advanced preterm labor, which is
      unresponsive to tocolysis because of the inflammation. Intra-amniotic
      inflammation may sensitize the fetus to postpartum stresses or initiate early
      GM/IVH in utero via cytokine effects on cardiovascular instability.

PMID- 8579657
TI  - A random single Doppler study of the umbilical artery in the evaluation of
      pregnancies complicated by diabetes.
AB  - To evaluate a random single Doppler study of the systolic to diastolic ratio of
      the umbilical artery as a predictor of perinatal outcome in diabetic pregnancies,
      a prospective double-blind study was performed in 92 diabetic pregnant women
      between 28 and 40 weeks of gestation. Main outcome measures were perinatal
      outcome: group A, normal outcome; group B, poor outcome. The sensitivity and
      specificity of the Doppler studies as a predictor of poor perinatal outcome were
      39% and 92%, respectively. The positive and negative predictive values were 54%
      and 86%, respectively. Our results suggest that the systolic to diastolic ratio
      of the umbilical artery offers no advantage over other well-established tests in
      the management of diabetic pregnancies.

PMID- 8579658
TI  - Spontaneous uterine rupture and hemoperitoneum in the first trimester.
AB  - Uterine rupture, a potentially catastrophic complication during pregnancy, has
      been reported to occur spontaneously in the second and third trimesters. We
      describe a case of spontaneous uterine rupture at 8 weeks' gestation in a 29-year
      old woman, who has a history of systemic lupus erythematosus. The diagnosis was
      established with the aid of ultrasound imaging. She underwent local excision of
      the perforated area of the uterus. Histologic examination revealed exuberant
      intermediate trophoblast. On follow-up, human chorionic gonadotropin (hCG) titers
      returned to normal over a 15-week period. We conclude that spontaneous uterine
      rupture can occur in the first trimester, and early utilization of ultrasound
      could help in the management of this serious condition.

PMID- 8579659
TI  - Transition from housestaff to nonphysicians as neonatal intensive care providers:
      cost, impact on revenue, and quality of care.
AB  - Nonphysician providers (NPP) increasingly fill roles traditionally performed by
      housestaff. Downsizing of a pediatric residency program prompted phased
      replacement of housestaff in a 26-bed neonatal intensive care unit (NICU).
      Subsidized education for neonatal nurse-practitioners, recruitment of physician
      assistants, and NPP leadership took place over 18 months, at which time all
      housestaff functions were assumed by NPP. Cost to establish the program, impact
      on hospital revenue under New York's prospective reimbursement system, and
      quality of care were evaluated. The net startup cost for the NPP program was
      $441,000 ($722,000 for education, salaries, staff replacement, and recruitment,
      partially offset by a New York State workforce demonstration project grant).
      Ongoing costs of the program are $1.2 million/yr (including salaries, off-hours
      medical backup, recruitment, administrative overhead, and loss of indirect and
      direct medical education reimbursement, partially offset by recaptured housestaff
      salaries and ancillary expense reductions). Access to care was maintained.
      Quality of care was assessed during the last 6 months of housestaff and the first
      6 months of full NPP staffing, revealing similar weight-specific survival, and
      improvement in documentation and compliance with immunization and blood
      utilization guidelines during the NPP period. NPP are expensive in comparison to
      housestaff. Revenue is minimally adversely affected, but access to NICU services
      and quality of care was preserved and in some cases enhanced with NPP. In the
      context of graduate medical education reform, staffing problems such as ours will
      be encountered increasingly in inpatient subspecialty settings.

PMID- 8579660
TI  - A rapid and safe method to detect fetal parvovirus B19 infection in amniotic
      fluid by polymerase chain reaction: report of a case.
AB  - Molecular amplification of parvovirus B19 DNA in an amniotic fluid sample was
      used to confirm the etiologic agent of a case with fetal hydrops. The polymerase
      chain reaction (PCR) method used is easy and fast to perform. We have a 2-year
      experience on its use in clinical parvovirus B19 diagnosis. The results are
      available within 1 day of sampling. In addition to strict laboratory standards,
      the use of two different sets of PCR primers and probes confirms positive
      findings. Positive parvovirus PCR on amniotic fluid confirms fetal parvovirus
      infection in cases of fetal nonimmune hydrops. Intrauterine transfusions may be
      necessary in cases with severe fetal anemia.

PMID- 8579661
TI  - Labor induction in patients with previous cesarean section.
AB  - To determine the efficacy and safety of labor induction in patients previously
      delivered by at least one low transverse cesarean section, a retrospective review
      was done at a single tertiary perinatal center, the University of Florida Health
      Science Center, Jacksonville. All patients with a previous cesarean section who
      required labor induction from 1988 until the end of 1992 were identified.
      Duration and outcome of labor induction, including mode of delivery, maternal and
      perinatal morbidity, and birth trauma, were evaluated. Of 160 patients with a
      previous cesarean, 50 (31.3%) had a repeat operation compared to 18 (11.2%) in
      the no previous cesarean group (p = 0.001, odds ratio = 3.59; 95% confidence
      interval, 1.98, 6.49). Women in the cesarean group had a higher incidence of
      operative vaginal deliveries, prolonged duration of the first and second stages
      of labor, rate and maximum dose of oxytocin infusion. One patient in the previous
      cesarean group experienced uterine rupture. There was no difference in the rate
      of infants with low 5-minute Apgar scores or with cord pH values less than 7.20.
      Labor induction in women with previous low transverse cesarean sections results
      in an acceptable rate of vaginal delivery and appears safe for both mother and
      fetus.

PMID- 8579662
TI  - In utero treatment of fetal goitrous hypothyroidism caused by maternal Graves'
      disease.
AB  - We present two cases of maternal Graves' disease complicated by fetal goitrous
      hypothyroidism. Both patients had elevated maternal thyroid-stimulating
      immunoglobulin and thyrotropic-binding inhibitory immunoglobulin antibody titers.
      Diagnosis of fetal hypothyroidism was made by cordocentesis, and serial
      injections of thyroxine into the amniotic fluid resulted in return to normal of
      fetal thyroid size and function at birth. Significance of in utero management of
      fetal hypothyroidism is discussed.

PMID- 8579663
TI  - Clinical significance of neurofibromatosis in pregnancy.
AB  - Neurofibromatosis (NF) is a common genetic disease that affects multiple organ
      systems. We studied eight women with NF and the outcome of their 14 pregnancies.
      One patient and her fetus died of a massive intracranial hemorrhage as a result
      of ruptured glioblastoma of the basal ganglia. The incidence of live birth and
      preterm labor were 50% and 28.6%, respectively. One of 14 pregnancies (7.1%)
      resulted in spontaneous abortion. There was also one growth-retarded fetus in
      this series (7.1%). Perinatal implications of this disease and management
      guidelines are discussed.

PMID- 8579664
TI  - Factors adversely affecting pregnancy outcome in the military.
AB  - This prospective study was undertaken to identify the significant risk factors
      associated with adverse pregnancy outcome in active-duty women. The deliveries of
      300 consecutive pregnancies of active-duty women were assessed for maternal-fetal
      outcome. The risk factors evaluated were: marital status, parity, race, smoking
      and alcohol consumption while pregnant, maternal weight gain during pregnancy,
      maternal height, and educational level. Two-thirds of these women were junior
      enlisted personnel (rank E-4 or below) and worked under demanding job conditions
      over which they had little control. Increased age as a risk factor was associated
      with a significant increase in pregnancy-associated complications of cesarean
      birth, operative vaginal delivery, pregnancy-induced hypertension, preterm labor,
      maternal transport for fetal indications, intrauterine growth restriction,
      intrauterine fetal death, postpartum hemorrhage, placenta previa, and 5-minute
      Apgar scores < 7 (p = 0.039). In gravidas more than 65 inches in height with a
      weight gain more than 42 pounds, there was a significant increase in the
      complications of pregnancy (p = 0.022). Interactions of these risk factors
      yielded a significant age (p = 0.025), maternal height (p = 0.007), and height
      times weight gain interaction (p = 0.006) association with pregnancy
      complications. The risk factors of advancing maternal age and tall stature with a
      maternal weight gain of more than 42 pounds are associated with increased
      pregnancy complications of active-duty women.

PMID- 8579665
TI  - Lipid levels of expeditioners in Antarctica: response to a reduced-fat, oleic
      acid and carbohydrate-enriched diet.
AB  - The study examined the effects of a reduced-fat, oleic acid and carbohydrate
      enriched diet on serum lipid profiles and body weight in the setting of an
      isolated Australian Antarctic station. A 12-week dietary intervention period was
      provided for 30 healthy, free-living expeditioners against a background diet
      typical of the Australian population. The diet tested a "modified U.S. Dietary
      Goals" regimen which increased oleic acid preferentially (29% energy from fat and
      46% from carbohydrate, polyunsaturated: monounsaturated: saturated fatty acid
      ratio [P:M:S] of 0.6:1.3:1.0, 30 g fibre/day, less than 300 mg cholesterol/day).
      During the intervention period, mean serum HDL-cholesterol (HDL-C) levels
      remained relatively stable while mean serum total cholesterol (TC) fell
      significantly (a fall of 0.95 mmol/l, p < 0.05). The mean serum triglyceride (TG)
      level rose initially (1.44 to 1.64 mmol/l, p < 0.05) but the level returned to
      baseline (1.41 mmol/l) by the end of the intervention period. The change in TG
      level was associated with increased dietary carbohydrate but not with changes in
      body weight, alcohol intake or season. The study demonstrates that a reduced-fat,
      oleic acid and carbohydrate-enriched diet can result in significant improvements
      in serum lipid profiles. The diet was acceptable to the subjects and was easily
      provided in Antarctica with unobtrusive changes to the typical Australian diet.

PMID- 8579666
TI  - Health and development in the Hudson Bay/James Bay region.
AB  - This paper reviews the literature on the health status of native people in the
      Hudson Bay/James Bay region of Canada, and explores the role of development in
      explaining discrepancies between observed and expected demographic and health
      trends. Relevant scientific literature was identified using computerised searches
      of bibliographic databases, as well as manual searches of selected journals and
      contact with experts. Although there was evidence that native people in Hudson
      Bay/James Bay have experienced significant improvements in health status, overall
      health status remains much worse than that of other Canadians. In many native
      communities, the prevalence and incidence of formerly infrequent chronic diseases
      have now surpassed those observed in non-native populations, and injuries,
      poisonings and violence are at epidemic levels. While these trends may be
      attributable to a variety of factors, environmental contamination and
      accompanying social, economic and cultural changes appear to play an important
      role.

PMID- 8579667
TI  - Residents' assessment of a community-based alcohol initiative in the Canadian
      Arctic.
AB  - This paper evaluated a community-based initiative to control alcohol abuse in the
      Canadian Arctic by identifying, from an Inuit perspective, what components have
      been successful in the reduction of alcohol abuse and what components require
      improvement. Data were collected through interviews with community leaders,
      supplemented by a broadly-based survey. The most successful strategy in the
      reduction of alcohol abuse was the imposition of restrictions on the availability
      of alcohol. Counselling services did to some extent heighten community awareness
      about the deleterious effects of alcohol misuse, but have had marginal impact on
      the reduction of abuse. Residents and community leaders involved in running the
      alcohol program believe that a combination of the establishment of self-help
      groups, further counsellor training, increased community support, and improved
      outreach strategies would provide a greater impetus for change leading to the
      reduction of alcohol abuse within the community.

PMID- 8579668
TI  - Thermoregulatory activity of motor units during human development.
AB  - The presented investigation was designed to elucidate whether age impacts the
      basic neurophysiological characteristics of motor unit (MU) thermoregulatory
      activity in human subjects. Human newborns and infants (aged from 7 days to 3
      years, n = 81) were exposed to ambient temperatures of 26-27 degrees C for 5-7
      minutes. The adults and elderly (18-76 years old, n = 90) were exposed to 10
      degrees C for 30-60 minutes. MU action potentials were followed by surface
      electromyography in the brachial triceps muscles, bilaterally. The firing rate of
      MUs (n = 245) during thermoregulatory muscle tonus was 7-35 Hz. Thirty six per
      cent of MUs (periodical MUs) of the newborns were firing by short trains of high
      frequency (20-35 Hz) discharges, with uniform interspike intervals. The other
      part of MUs in the newborns was stationary firing at frequencies from 12 to 20 Hz
      (stable MUs). No periodical MUs were found in infants and adults and elderly
      humans. MU firing rate at 18-60 years of age was 8-9 Hz, and was statistically
      significantly lower than in the ages over 60 years (9-11 Hz). These data allowed
      us to compute a parabolic dependence of MU firing rate on the age during
      thermoregulatory tonus: Fmu = 12.60-0.22A + 0.03A2 (r = 0.91; Fmu-MU mean firing
      rate, Hz; A-age, years).

PMID- 8579669
TI  - [27 years experiences with transtympanic aminoglycoside treatment of Meniere's
      disease].
AB  - BACKGROUND: Severe unilateral Meniere's disease is successfully treated
      intratympanically with ototoxic antibiotics. Gentamicin sulfate (Refobacin) gives
      the best results. The only disadvantage is that gentamicin may damage hearing in
      the treated side. Therapy is easier in patients with marked hearing loss prior to
      treatment. PATIENTS AND METHOD: Since 1976 we treated 61 patients by injecting 8
      12 mg Refobacin (0.2-0.3 ml) into the external auditory meatus between two and
      five times per day. By creating slight pressure (Politzer bag) the liquid is
      transported into the middle ear via a ventilating tube. From here it penetrates
      through the windows. The slightest indication of inner ear reaction was grounds
      for immediately terminating treatment. RESULTS: In 54 of our 61 patients (follow
      up 2-17 years) we were completely successful. Three further patients continued
      having very rare and weak spells, yet we regard them as being practically healed.
      We did not succeed in four of our cases. Twenty-nine patients suffered hearing
      loss. Hearing was mostly poor prior to therapy. CONCLUSIONS: Transtympanic
      gentamicin therapy provides very good results in severe cases of unilateral
      Meniere's disease. Spells of vertigo and vomiting are controlled. We propose
      individual dosage depending on hearing threshold and intensity of symptoms.

PMID- 8579670
TI  - [Reduced nutritional status enhances ototoxicity].
AB  - BACKGROUND: This study investigates whether the nutritional state of guinea pigs
      is a risk factor for the ototoxic side effects of cisplatin, gentamicin, and
      gentamicin in combination with ethacrynic acid. METHODS: A normal nutritional
      state was maintained with a standard 18.5% protein diet while nutritional
      deficiency was produced by feeding a 7% protein diet. Hearing loss was measured
      by auditory evoked brainstem responses. RESULTS: Guinea pigs on the low protein
      diet had a significantly higher drug-induced hearing loss. Cisplatin-induced
      hearing loss was 32 dB in undernourished animals but 10 dB in normal animals (18
      kHz). The difference for gentamicin was 74 dB versus 42 dB (18 kHz). Gentamicin
      in combination with 20 mg ethacrynic acid/kg body weight produced a hearing loss
      of 95 dB in animals on a low protein diet and 12 dB in animals on a full protein
      diet. The enhanced ototoxicity was not based on differences in drug
      pharmacokinetics since serum levels of platinum and gentamicin did not differ
      between the groups. CONCLUSIONS: These results demonstrate that the severity of
      ototoxic side effects is influenced by nutritional factors. They also imply that
      animals on a restricted diet may be a more appropriate model for severely
      compromised patients undergoing pharmacotherapy.

PMID- 8579671
TI  - [Diagnostic intra-meatal acoustic neurinoma--the role of acoustically evoked
      brain stem potentials and other otoneurologic studies].
AB  - BACKGROUND: Today intracanalicular acoustic neuromas are diagnosed very early by
      magnetic resonance imaging (MRI). The purpose of this study was to test the
      capability of brainstem evoked response audiometry (BERA) for detecting these
      small tumors. PATIENTS: Seventeen of 91 consecutive cases with acoustic neuromas
      treated at our department suffered from purely intracanalicular tumors. For these
      17 patients we reviewed their medical history, clinical otoneurologic
      examination, audiometry, auditory evoked brainstem audiometry,
      electronystagmography, and MRI studies. RESULTS: In 13 of 17 patients (76.5%)
      auditory evoked brainstem audiometry was indicative of a suspected retrocochlear
      lesion, whereas in 4 cases BERA did not indicate such a lesion. CONCLUSIONS: The
      symptoms of these patients are described in detail. The role of auditory evoked
      brainstem audiometry and other otoneurologic test methods for detection of
      intracanalicular acoustic neuromas will be discussed.

PMID- 8579672
TI  - [Effect of the phytogenic secretolytic drug Gelomyrtol forte on mucociliary
      clearance of the maxillary sinus].
AB  - BACKGROUND: To date, there has not been sufficient experimental evidence to
      demonstrate the pharmacological effect of secretolytic and mucolytic drugs.
      METHODS: Scintigraphic studies to detect the mucociliary clearance in the
      maxillary sinus before and after application of the secretolytic drug Gelomyrtol
      forte were performed on four healthy persons and one patient after sinus surgery.
      The most important parameter was the mucociliary transport velocity of the
      "region of interest-maxillary sinus" and the increase of radioactivity
      accumulated in a tampon placed in the middle meatus of the nose. Measurements
      were done with a gamma-camera, 99 m Technetium-sulphurcolloid was used as the
      radiopharmacentical. A dose of 1 MBq in 0.2 ml NaCl-solution was injected into
      the maxillary sinus. RESULTS: The results show a clear increase of mucociliary
      transport velocity in the maxillary sinus after intake of secretolytics in
      connection with an increase of radioactivity in the tampon. DISCUSSION: The
      results can be explained by the secretolytic and secretomotoric effects of the
      investigated drug. CONCLUSION: The study reveals that ethereal oils have
      secretolytic effects and also have a pharmacological effect on the mucociliary
      apparatus.

PMID- 8579673
TI  - [Surgical therapy of oropharyngeal carcinoma within the scope of
      interdisciplinary tumor surgery].
AB  - BACKGROUND: The results of the surgical therapy of patients with extensive
      squamous cell carcinoma of the oropharynx and their lymph node metastasis,
      postoperative follow-up, and rehabilitation depend on the collaboration between
      ear, nose, and throat surgeons and maxillofacial surgeons. Modern reconstruction
      techniques permit single-session surgical treatment with a reduced period of
      hospitalization. The most important therapeutic aim is to improve patient well
      being. PATIENTS: Over a period of two years, 45 patients underwent the same
      surgical procedure. These patients were all in stages III or IV of their disease.
      RESULTS: This procedure consists of a temporary lateral osteotomy of the mandible
      with or without resection of the mandible, to provide broad exposure of the tumor
      of the oropharynx. Apart from the broad exposure, the advantage of this surgical
      method lies in simple reconstruction using a pedicled and microanastomosed flap.
      Internal fixation with six and four-hole titanium plates is a reliable method for
      restoring the stability of the mandible. In six patients, complications occurred
      in connection with the plate fixation. In four patients, we observed
      osteomyelitis of the fragment fissure or sequestration. Plate fracture and
      pseudarthrosis occurred in one patient each. CONCLUSIONS: In our clinical
      experience, the microvascular anastomosed radial flap proved to be the ideal free
      soft tissue transplant. One of its primary advantages is its plasticity and hence
      good post-therapeutic functional results. The jejunal flap has become less
      significant them the radial flap; the advantage of mucous membrane transfer is
      lost after radiation and a corresponding postoperative interval. In patients with
      large, voluminous defects, the use of myocutaneous flaps, especially from the
      latissimus dorsi, is still justified.

PMID- 8579674
TI  - [Determination of genetic susceptibility for development of squamous epithelial
      carcinomas of the had and neck with bleomycin-induced chromosome instability].
AB  - BACKGROUND: Cigarette smoking is a well established risk factor for head and neck
      squamous cell carcinoma. However, data on smoking history are not sufficient to
      predict which patients are at high risk for the development of multiple primary
      tumors. It is hypothesized that both exposure to carcinogens and individual
      susceptibility determine cancer risk. The aim of this study was to investigate
      whether a possible individual susceptibility for head and neck squamous cell
      carcinoma was related to the outcome of the mutagen sensitivity assay, which was
      adopted from Hsu and colleagues. METHODS: Cultured peripheral blood lymphocytes
      were treated for five hours with 30 mIU/ml of bleomycin, and sensitivity was
      estimated by the mean number of chromatid breaks per cell scored in 100
      metaphases of duplicate cultures. RESULTS: It was shown that using this standard
      mutagen sensitivity assay, a person's sensitivity can be reproducibly measured.
      Age had a significant but small contribution, whereas gender and tobacco and
      alcohol use had no influence on the outcome of the assay. Therefore, we consider
      this sensitivity for the DNA damaging effect of bleomycin constitutional. A
      retrospective study showed that the breaks per cell in head and neck squamous
      cell carcinoma patients (0.96 +/- 0.31; n = 52) were significantly higher (p <
      0.001) than in control persons (0.77 +/- 0.19; n = 50). In addition, head and
      neck cancer patients who had already developed multiple primary tumors had a
      break per cell level (1.20 +/- 0.47; n = 20) which was even significantly higher
      (p < 0.025) than in patients with one primary tumor. CONCLUSION: We hypothesize
      that mutagen sensitivity reflects an individual's sensitivity vor DNA damaging
      agents. The extremely high sensitivity in patients with multiple primary tumors
      suggests that mutagen sensitivity is a phenotype reflecting a person's
      susceptibility to head and neck cancer. We postulate that mutagen sensitivity in
      combination with smoking history can be used to identify those patients at
      highest risk for the development of multiple primary tumors.

PMID- 8579675
TI  - [Animal experiment studies of laser effects on lymphatic vessels. A contribution
      to the discussion of laser surgery segmental resection of carcinomas].
AB  - BACKGROUND: The potential effect of laser surgery on the process of lymphogenic
      metastases is subject to controversy. In this context it would be of interest to
      identify a morphological basis for an increased intraoperative entry of tumor
      cells into the lymphatic system during resection of advanced carcinomas in two or
      more pieces via laser surgery. METHODS: The tissue effect of laser incisions (CO2
      laser: 3030 W/cm2; Nd:YAG-laser: 3180 W/cm2) on the lymphatics of the buccal
      mucosa in 60 Wistar rats was studied by light microscopy, histochemistry, and
      lymphography during surgery and subsequent wound healing. These incisions were
      compared to conventional scalpel incisions. RESULTS: No lymphatic vessels were
      detected in the zone of carbonization, they were mostly dilated whereas in the
      zone of edema. In the zone of necrosis, the lymphatic were occluded by
      coagulation. The mid and long-term effect of the laser light on the regeneration
      of lymphatics was mainly correlated to wound healing which--when compared to
      conventional surgery--is delayed after laser surgery. Following scalpel incision,
      the first lymphatics enter the wound region after 4 days, a opposed to 10 days
      following laser surgery. Intact continuity of the lymphatic vasculature was
      detectable 15 days after scalpel incision and 42 days after laser incision. The
      regeneration of lymphatics was slightly more delayed after CO2 laser incision
      than after Nd:YAG laser incision. CONCLUSION: The results of this study do not
      indicate that the laser resection of carcinomas facilitates an intraoperative
      entry of tumor cells into the lymphatic vasculature. These experimental results
      verify clinical reports which do not observe an increased frequency of
      postoperative metastases after laser resection of carcinomas in two or more
      pieces.

PMID- 8579676
TI  - [Examination technique of ultrasound follow-up of pharyngeal closure after
      laryngectomy].
AB  - BACKGROUND: The pharyngocutaneous fistula presents the most common complication
      after laryngectomy. Despite applying methods of pharyngeal closure, local factors
      such as irradiation may cause healing disturbances and the development of
      pharyngeal fistula. Before the nasogastric feeding tube is removed, an additional
      radiologic control with water-soluble contrast medium is recommended in
      literature in case of normal clinical healing. METHODS: The radiologic method was
      compared with a newly developed sonographic examination technique. Using the so
      called "aerophagia maneuver" in sonography, an arising of peripharyngeal air
      before the "aerophagia maneuver" or a peripharyngeal mass lesion was an uncertain
      criterion for a pharyngeal fistula. Peripharyngeal air may be seen also due to
      infection with anaerobic bacteria, and peripharyngeal mass lesion may be caused
      by seroma or hematoma. In sonography, tissular air is seen typically, in a
      hyperechoic reflex with distal repetitions. RESULTS: Radiologic examination of
      the pharynx in 18 laryngectomy patients revealed fistulas in three cases.
      CONCLUSIONS: Our experiences have shown so far that sonographic examination in
      combination with the so-called "aerophagia maneuver" prove to be reliable or
      ascertaining pharyngeal closure after laryngectomy.

PMID- 8579677
TI  - [Allogeneic transplantation and HIV infection: studies of HIV-infected tissue].
AB  - BACKGROUND: Because of the limited availability of autologous tissue, stored
      allograft is commonly used. Before grafting, bank tissue is subjected to chemical
      preservation procedures. This procedure is important to diminish antigenicity and
      to inactivate possible inherent viruses. The aim of this study was to determine
      the influence of different chemical preservation procedures like Cialit,
      Merthiolate, and formaldehyde on the presence of HIV DNA. METHODS: HIV-infected
      tissues were obtained from eight HIV-positive patients and examined using the
      polymerase chain reaction (PCR). RESULTS: After chemical treatment, we could
      observe the presence of HIV DNA in all examined tissues. CONCLUSIONS: The
      findings indicate the importance of the mandatory serological screening and
      selection in donor patients.

PMID- 8579678
TI  - [Lymphoepithelial carcinoma of the nasolacrimal duct--a case report].
AB  - PATIENT: A 59-year-old patient with an extremely rare lymphoepithelioma of the
      nasolacrimal duct was treated with radiation therapy and chemotherapy. RESULTS: A
      complete remission was achieved. Serious side effects and late effects have,
      until now, not been observed. The patient has been free of tumor for two and a
      half years. CONCLUSIONS: With this case report, the authors wish to draw the
      attention of otorhinolaryngologists to this unusual tumorsite. They emphasize
      that good results can be achieved with a combination of radiation therapy and
      chemotherapy, if surgery is not possible.

PMID- 8579679
TI  - [Delayed stenosis after esophageal reconstruction with colon interposition 35
      years ago].
AB  - BACKGROUND: The long-term complication of an anastomotic stenosis with a
      poststenotic diverticulum in the case of lye chemical burn of the esophagus at
      the age of 2 prompted us to present this very rare case, in which 35 years ago
      the defect was bridged with a section of colon. PATIENTS: In case in point,
      secondary surgical correction was performed six years after the accident. Thirty
      five years later, our patient developed a stenosis of the proximal esophagus
      which made surgical intervention necessary. RESULTS: In this paper, we describe
      the problems caused by chemical burns in this case (lye), the surgical treatment,
      and possible complications. CONCLUSIONS: Reliable procedures include
      reconstruction with a jejunal transplant, pectoralis major flap, microvascular
      myocutaneous flap, and retrosternal plastic surgery of the colon. A report on
      diagnostic procedure and operative care is presented.

PMID- 8579680
TI  - Structure and characterization of isopyoverdin from Pseudomonas putida BTP1 and
      its relation to the biogenetic pathway leading to pyoverdins.
AB  - Pyoverdin type siderophores produced by six fluorescent Pseudomonas strains
      isolated from different rhizospheres were purified and characterized. The
      purified ferri-pyoverdins were tested for their ability to promote the growth of
      other strains grown under iron deficiency conditions. Only the one obtained from
      Pseudomonas putida BTP1 did not act as a growth promoter. The structure of the
      BTP1 siderophore was elucidated by spectroscopic methods and degradation studies.
      It turned out that it contains a chromophore which differs from the one typical
      for pyoverdins insofar as it carries the carboxyl group in 3- rather than in 1
      position ((3S)-5-amino-1,2-dihydro-8,9-dihydroxy-3H-pyrimido[1,2a]quinoline-3-
      carboxylic acid). The amino group of the chromophore is substituted with the 5
      carboxyl group of L-glutamic acid and its carboxyl group with the N-terminus of
      the peptide L-Asp-L-Ala-L-Asp-D-N5-Ac-N5-OH-Orn-L-Ser-L-c-N5-OH-Orn. This
      isopyoverdin fits into the biogenetic scheme which postulates ferribactins as the
      precursors of pyoverdins.

PMID- 8579681
TI  - Genes leave their characteristic marks on the melting profile of plasmid DNAs.
AB  - High resolution melting profiles of four linearised plasmids (pUC9, pGV403, pHP2,
      and pBR322) were recorded by means of UV absorbance vs. temperature scanning. The
      set of transitions obtained for each plasmid are compared to each other and to
      the transitions obtained for their excised particular antibiotica resistance
      gene. It can be shown that each gene leaves a characteristic mark on the melting
      profile of its parental plasmid.

PMID- 8579682
TI  - Fusiogenic activity of natural amphiphiles, 5-n-alkylresorcinols in a yeast
      protoplast system.
AB  - Two homologues of cereal grain resorcinolic lipids, 5-n-heptadecylresorcinol and
      5-n-heptadecenylresorcinol studied in the system employing yeast cell protoplasts
      showed marked fusiogenic activity. The frequency of hybrid formation induced by
      studied amphiphiles was significantly higher than that obtained with the use of
      40% (w/v) polyethylene glycol 4000. The resorcinolic lipids as fusion-inducing
      agents did not affect regeneration of the cellular wall. The fusiogenic activity
      of resorcinolic lipids lost when calcium ions were absent in the medium.
      Fusiogenic activity of studied amphiphiles is related to their ability to induce
      non-bilayer structures within the cellular membranes.

PMID- 8579683
TI  - Cooperative binding of the organophosphate paraoxon to the (Na+ + K+)-ATPase.
AB  - Paraoxon, the main active metabolite of the organophosphorus insecticide
      parathion, exerted a dose-dependent inhibitory effect on the activity of pig
      kidney (Na+ + K+)-ATPase contained in microsomal fraction and purified from it.
      Substrate kinetics studies revealed the existence of two active sites with high
      and low affinity to ATP. The Dixon analysis of the mode of the inhibition
      indicated its noncompetitive character. The purified enzyme was more affected
      than enzyme contained in the microsomal fraction. The inhibition constant Ki
      ranged from 73 to 245 microM depending on the type of preparation. The Hill
      coefficient (n) fulfilled the relationship 1 < n < 3. These properties of the
      interaction suggest the cooperative binding of paraoxon to the enzyme. An
      indirect mechanism of the interaction was proposed: paraoxon could inhibit the
      activity of the (Na+ + K+)-ATPase by excluding the enzyme protein from its normal
      lipid milieu.

PMID- 8579684
TI  - Different expression of esterase variants in rat hepatic and hepatoma-derived
      cell lines detected by electrophoresis.
AB  - Esterases in nine rat hepatic and hepatoma-derived cell lines and normal rat
      liver homogenate were detected by polyacrylamide gel electrophoresis coupled with
      active staining with alpha-naphthyl acetate or butyrate as a substrate. The
      esterase band patterns of the non-cancerous and oncogene-transformed cell lines
      were alike, but different from those of hepatoma cell lines and normal rat liver
      homogenate. The former groups of cells might have completely lost the
      characteristics of rat liver parenchymal cells, or else they might have their
      origin at cells other than liver parenchyma. The esterase patterns of the
      hepatoma cell lines (e.g., McA-RH7777) and the normal rat liver highly resembled
      with each other, exemplifying the slight biochemical deviation of cancer from
      normal cells. However, two-dimensional electrophoretogram for the McA-RH7777 cell
      line showed a prominent esterase spot (pI 6.0-M(r) 110 kDa) that was lacking in
      the normal liver. This result indicates that there is invariably some change in
      esterase expression between the cancer cells and the normal liver cells.

PMID- 8579685
TI  - Bioactive alkaloids from the tropical marine sponge Axinella carteri.
AB  - Analysis of the tropical marine sponge Axinella carteri afforded six unusual
      alkaloids, including the new brominated guanidine derivative 3-bromo
      hymenialdisine. The structure elucidation of the new alkaloid is described. The
      alkaloid patterns of sponges collected in Indonesia or in the Philippines were
      shown to be qualitatively identical suggesting de novo synthesis by the sponge or
      by endosymbiontic microorganisms rather than uptake by filter feeding. All
      alkaloids were screened for insecticidal activity as well as for cytotoxicity.
      The guanidine alkaloids hymenialdisine and debromohymenialdisine exhibited
      insecticidal activity towards neonate larvae of the polyphagous pest insect
      Spodoptera littoralis (LD50s of 88 and 125 ppm, respectively), when incorporated
      into artificial diet and offered to the larvae in a chronic feeding bioassay. The
      remaining alkaloids, including the new compound were inactive in this bioassay.
      Cytotoxicity was studied in vitro using L5178y mouse lymphoma cells.
      Debromohymenialdisine was again the most active compound (ED50 1.8 micrograms/ml)
      followed by hymenialdisine and 3-bromohymenialdisine, which were essentially
      equitoxic and exhibited ED50s of 3.9 micrograms/ml in both cases. The remaining
      alkaloids were inactive against this cell line.

PMID- 8579686
TI  - Xanthine oxidase and xanthine dehydrogenase from an estivating land snail.
AB  - During arousal from estivation in land snails, Otala lactea, active metabolic
      functions are restored within minutes and oxygen consumption increases
      dramatically. During the transition from the hypoxic conditions of estivation to
      normoxia it is possible that xanthine oxidase (XO) in hepatopancreas contributes
      to the observed lipid peroxidation. Using a fluorometric assay that is based on
      the oxidation of pterin, the activities and some properties of XO and XO+XDH (sum
      of XO and xanthine dehydrogenase activities) were measured in hepatopancreas
      extracts. Km values for pterin for XO and XO+XDH were 9 and 6 microM,
      respectively, and the Km of XDH for methylene blue was 5 microM. Both XO+XDH and
      XO activities were inhibited by allopurinol (I50 = 2 microM), pre-incubation at
      40 degrees C, and by 5 min H2O2 pre-exposure. Inclusion of azide in the reaction
      promoted a rise of approximately 70-fold in the inactivation power of H2O2 due to
      inhibition of high endogenous catalase activity. The I50 for H2O2 of XO+XDH and
      XO activities in the presence of azide was 0.04 and 0.11 mM, respectively. Unlike
      the situation for mammalian XO, a previous reduction of O. lactea XO (by pterin)
      was not necessary to make the enzyme susceptible to H2O2 effects. Interestingly,
      methylene blue partially prevented both heat- and H2O2-induced inactivation of
      XO+XDH activity. These data indicate that the formation of an enzyme-methylene
      blue complex induces protection against heat and oxidative damage at the FAD
      active site. Both XO and XO+XDH activites were significantly higher in snails
      after 35 days of estivation compared with active snails 24 h after arousal from
      dormancy. The ratio of XO/(XO+XDH) activities was also slightly increased in
      estivating O. lactea (from 0.07 to 0.09; P < 0.025). XO activity was 0.03
      nmol.min-1.mg protein-1 in estivating snails. Compared with hepatopancreas
      catalase, XO activity is probably too low to contribute significantly to the net
      generation of oxyradicals, and hence to peroxidative damage. Rather, the low
      potential of XO to induce oxidative stress may constitute an adaptive advantage
      for O. lactea during arousal periods.

PMID- 8579687
TI  - Homocysteine-induced oxidative damage: mechanisms and possible roles in
      neurodegenerative and atherogenic processes.
AB  - Increased blood plasma concentrations of the sulphur amino acid homocysteine
      ("homocysteinemia") have been brought into context with neurodegenerative and
      arteriosclerotic symptoms and diseases. We recently reported on biochemical model
      reactions on the prooxidative activity of homocysteine including the
      desactivation of Na+/K(+)-ATPases and hemolysis of erythrocytes (Preibisch et
      al., 1993). In this communication we extend our model reactions including the
      oxidation of methionine, metabolization of pyridoxalphosphate and
      dihydroxyphenylalanine, desactivations of transaminases and peroxidation of low
      density lipoprotein.

PMID- 8579688
TI  - A receptor interaction model for phenylcarbamate local anesthetics.
AB  - We report here a molecular modeling study of selected conformationally
      constrained phenylcarbamate local anesthetics in relation to the available
      pharmacological data that enabled us to develop a receptor-interaction model for
      this class of drugs. The validity of the model was confirmed on other semirigid
      analogues prepared for this study. The results suggest that the phenyl ring is
      most likely involved in a stacking interaction with a complementary receptor site
      and the tertiary ammonium group is capable of both hydrogen bonding and
      lipophilic interactions.

PMID- 8579690
TI  - Effect of platinum(II) complexes of benzoic and 3-methoxybenzoic acid hydrazides
      on Saccharomyces cerevisiae.
AB  - The inhibitory effect of benzoic acid hydrazide (bah) and 3-methoxybenzoic acid
      hydrazide (mbah) on Saccharomyces cerevisiae strains has been compared to that of
      their platinum(II) complexes: cis-[Pt(mbah)2X2], cis-[Pt(NH3)(mbah)Cl2].0.5 H2O,
      cis-[Pt(mbah)2X2] and cis[Pt(NH3)(mbah)Cl2] (mean = Cl, Br = I), and cis
      [Pt(NH3)2Cl2]. The minimal inhibitory concentrations for bah and mbah were 5000
      20,000 microM whereas for their Pt(II) complexes they were much less (25-800
      microM) and did not exceed these of cisplatin (100-800 microM). The activity of
      the Pt(II) complexes of bah and mbah varied in wide ranges for the different
      yeast strains tested. Osmotically unstable mutants were found to be more
      susceptible. The most active complexes were [Pt(NH3)(bah)Cl2].0.5 H2O and
      [Pt(NH3)(mbah)Cl2].

PMID- 8579689
TI  - Action of hypochlorous acid on polymeric components of cartilage. Use of 13C NMR
      spectroscopy.
AB  - It is a well known fact that neutrophil-derived hypochlorous acid plays an
      important role in cartilage destruction during rheumatoid arthritis. It has been
      shown by 1H NMR spectroscopy in a previous paper (Schiller et al. (1994), Biol.
      Chem. Hoppe-Seyler 375, 167-172) that sodium hypochlorite affects primarily the N
      acetyl side chains of polymeric carbohydrates of cartilage like
      chondroitinsulphate and hyaluronic acid. An instable intermediate, likely to be a
      chloramine, is involved in these processes. The present paper deals with the
      application of carbon NMR spectroscopy for the study of these degradation
      processes, because carbon NMR gives the opportunity to detect changes on the
      single sugar ring carbons. Although it was not possible to prove the involvement
      of an intermediate, because of its fast hydrolysis, we were able to show that the
      reaction between sodium hypochlorite and N-acetylglucosamine affects mainly the
      side chain, accompanied by the formation of acetate. The application of a large
      excess of sodium hypochlorite leads to a breakdown of the carbohydrate ring under
      the formation of formiate.

PMID- 8579691
TI  - Specificities of rabbit antisera to multiple antigen (MAP) peptides.
AB  - Two multiple antigen peptides consisting of 6 and 7 aminoa cid residues,
      respectively, plus a 12-residue fragment, used as a control, all linked to a
      polylysine core, were used as immunogens in rabbits in order to obtain an immune
      response. Rabbit antisera against such polymers were then tested in ELISA against
      a panel of antigens in order to analyze the specificities of the resulting
      antibodies. The responses were different for all three immunogens, being
      partially or totally directed, for two of the three compounds, including the 12
      residue control MAP peptide, against the polylysyl core, which is considered as
      non immunogenic. The third MAP polymer was practically unable to elicit an immune
      response.

PMID- 8579692
TI  - Self-organized criticality and dynamic instability of microtubule growth.
AB  - We have shown that the distribution of lengths of site nucleated microtubules
      obey an algebraic power law relationship D(s) = A s(-tau), where D(s) is relative
      number of microtubules with length s, A and tau are constants. This relationship
      indicates the possibility of a self-organized criticality in the dynamic
      instability of microtubule growth.

PMID- 8579693
TI  - A standardized instrument to assess hazards for falls in the home of older
      persons.
AB  - Hazards in the home are implicated in up to half of all falls among older
      persons. Yet, the instruments used to identify these hazards usually have been
      unstandardized, have lacked specific definitions of hazards, and have not been
      evaluated. Therefore, in 1988, as part of the Study to Assess Falls among the
      Elderly, in Miami Beach, Florida, the authors evaluated the reliability of a
      standardized instrument used for assessing the training of evaluators and
      assessing home environments. Based on up to 176 observations for each potential
      hazard, the interviewers' assessment of hazards such as throw rugs, tripping
      hazards, light switch hazards, and hazardous bath surfaces had good overall
      reliability (kappa = 0.65-0.92). Their assessment of grab-bars and hazardous
      furniture was unreliable (kappa = 0.18-0.35). Variations in the reliability
      reflect the difficulty in creating definitions that are simple to be understood
      and used, yet detailed enough to produce sensitive and specific survey items.
      Investigators studying falls among older persons should use standardized
      definitions to train evaluators and assess environmental hazards.

PMID- 8579694
TI  - Daytime running lights as a vehicle collision countermeasure: the Swedish
      evidence reconsidered.
AB  - In Sweden the use of daytime running lights (DRL) was made mandatory on 1 October
      1977 for all motor vehicles at once, during all seasons and for all areas.
      According to a study conducted by Andersson and Nilsson (1981) [Andersson and
      Nilsson. VTI Swedish Road and Transport Research Institute, Report No. 208A;
      1981] the introduction of DRL resulted in a reduction of 11% of multiple
      accidents during daytime. In many discussions on the effectiveness of DRL, these
      findings have been considered as the strongest evidence that the use of DRL is an
      effective vehicle collision countermeasure. The present study reexamines this
      evidence and shows that the reported 11% effect of DRL in the Swedish study is
      spurious. The effect is mainly the result of the application of a model that
      shows selective effects of DRL through modelling of unexplained changes in the
      number of single accidents. It is concluded that the Swedish data fail to show a
      clear effect of DRL.

PMID- 8579695
TI  - The hit-and-run in fatal pedestrian accidents: victims, circumstances and
      drivers.
AB  - Hit-and-run pedestrian fatalities are classified as to victim characteristics,
      accident circumstances and driver characteristics. Over 18,000 pedestrian
      fatalities are reported in the Fatal Accident Recording System for 1989-1991.
      Twenty percent of the drivers involved left the accident scene. Children and
      senior citizens are the least likely to be left. Drivers more commonly run in
      urban areas, outside the South, on weekends and at night. Comparing motorists who
      left the scene but were later identified with the drivers who remained, drivers
      aged 66 and older are half as likely as younger drivers to leave the accident
      scene and male drivers are 60% more likely than female drivers to run. Drivers
      with previous driving while intoxicated arrests are twice as likely to run as
      those with no such arrests. Forty-nine percent of hit-and-run motorists involved
      in pedestrian fatalities are ultimately identified by the police. Other factors
      constant, drivers are more likely to be identified if the victim was female or a
      child. Drivers are identified 2.5 times as often when the incident occurred in
      daylight. Drivers appear to run more often when they are at fault and will be
      severely punished (e.g. when they are intoxicated) and when it is likely that
      they can escape detection (e.g. at night).

PMID- 8579696
TI  - Alcohol and non-fatal injury in the U.S. general population: a risk function
      analysis.
AB  - This paper reports a risk function analysis of average daily volume of alcohol
      consumed and the frequency of consuming 5 or more drinks during a single day with
      reporting an injury in a probability sample of the U.S. adult household
      population living in the 48 contiguous states. The data are from the 1990
      National Alcohol Survey on a weighted sample of 1150 respondents, 748 of whom
      were current drinkers. Risk of injury was found to increase with an average daily
      volume of 1 drink for both males and females and for those 30 and younger and
      those over 30, and to increase with a frequency of consuming 5 or more drinks on
      one day more often than twice a year. These data suggest that risk for injury may
      be increased at relatively low levels of consumption and, if so, that preventive
      efforts aimed at more moderate drinkers may have a greater impact on the
      reduction of alcohol-related accidents than efforts focused on heavier drinkers
      who are fewer in number.

PMID- 8579697
TI  - Spatial analysis of Honolulu motor vehicle crashes: I. Spatial patterns.
AB  - This study describes spatial patterns in Honolulu motor vehicle accidents for
      1990. A method for geo-coding accident locations is utilized with approximately
      98% of the crash locations being identified. Spatial software tools are developed
      for describing the degree of spatial concentration. The spatial patterns of
      different types of accidents and accidents for every hour of the day, weekdays
      and weekends separately, are analyzed. Accidents spatially fluctuate dynamically,
      as a response to changing traffic patterns and volume. Generally, most accidents
      are closer to employment centers than to residential areas. In the suburban and
      rural areas, however, accidents are more likely to involve fatalities or serious
      injuries and be related to night-time driving and alcohol. It is shown that these
      conditions spatially correlate with single-vehicle crashes and crashes with
      opposite direction vehicles. The spatial patterns point to the limits of
      "blackspot" analysis.

PMID- 8579699
TI  - A filter model to describe bias in official statistics on alcohol-related
      injuries.
AB  - The paper describes a filter model that can be used to explore the possible
      biases that occur in reporting of alcohol-related injuries. These biases occur
      because of loss of data at various stages of injury reporting systems. The filter
      model consists of four levels or incidences, with a filter between each level.
      Level 1 is the total incidence of alcohol-related injuries. Level 2 is the
      incidence of reported alcohol-related injuries. Level 3 is the incidence of
      reported alcohol-related injuries where the contribution of alcohol has been
      correctly identified. Level 4 consists of official statistics on alcohol-related
      injuries. Between each of these levels is a filtering mechanism that allows some
      but not all data to pass through to the next level. The paper describes the
      nature of data at each level and the mechanisms operating at each filter to
      result in progressive loss of data. Estimates are provided regarding the extent
      of loss of data at each filter. Suggestions are provided for improving the
      quality of official statistics on alcohol-related injuries.

PMID- 8579698
TI  - Spatial analysis of Honolulu motor vehicle crashes: II. Zonal generators.
AB  - The spatial relationship between activities which generate trips and motor
      vehicle accidents is examined and applied to the City and County of Honolulu for
      1990. A method is described for examining spatial variations in motor vehicle
      accidents, aggregated into small geographical areas. A spatial lag model is
      developed which examines the zonal relationship of motor vehicle accidents to
      population, employment and road characteristics. The resulting model is tested
      for each hour of the day, weekdays and weekends separately. The predictors of
      accidents fluctuate according to different trip generating activities and change
      considerably over the day. The method can generate expected accidents, allowing
      for an identification of areas which have higher than expected levels. It is
      argued that this method focuses attention on characteristics of neighborhoods and
      areas, and not just on the road system.

PMID- 8579700
TI  - Risk factors for injury: similarities and differences for traffic crashes and
      other causes.
AB  - Actions to prevent injury may address either individual behaviour or population
      practice. Factors associated with injuries in a variety of circumstances may be
      best suited to prevention at the level of population whereas more specific causes
      would not be. Data from the Ontario Health Survey were used to assess the
      similarities and differences between risk factors and injury in traffic crashes,
      at work and in other circumstances. Respondents reporting injury were compared
      with age- and sex-matched controls reporting no injury for reported alcohol
      ingestion, binge drinking and drinking and driving. In addition, data on the use
      of licit and illicit drugs, occupation and other demographic factors were
      compared. Variables showing consistent associations with injury included drug
      use, some measures of alcohol ingestion and reports of co-existing chronic
      disease. Many variables showed a variable pattern, including occupation,
      education and income. In many instances, these differences reflected differences
      in exposure to risk. Efforts at prevention related to alcohol or medication could
      be broadly based, whereas for other factors, more targeted prevention efforts
      would be appropriate.

PMID- 8579701
TI  - The effects of a mobile telephone task on driver behaviour in a car following
      situation.
AB  - The effects of a mobile telephone task on young and elderly drivers' choice
      reaction time, headway, lateral position, and workload were studied when the
      subjects were driving in a car-following situation, in the VTI driving simulator.
      It was found that a mobile telephone task had a negative effect upon the drivers'
      choice reaction time, and that the effect was more pronounced for the elderly
      drivers. Furthermore, the subjects did not compensate for their increased
      reaction time by increasing their headway during the phone task. The subjects'
      mental workload, as measured by the NASA-TLX, increased as a function of the
      mobile telephone task. No effect on the subjects' lateral position could be
      detected. Taken together, these results indicate that the accident risk can
      increase when a driver is using the mobile telephone in a car following
      situation. The reasons for the increased risk, and possible ways to eliminate it,
      are also discussed.

PMID- 8579702
TI  - Crash pulse recorder--validation in full scale crash tests.
AB  - Estimation of the accident severity is a fundamental requirement in accident
      reconstruction and analysis. Accident severity can be measured in many different
      ways, but in frontal collisions change of velocity, energy equivalent speed or
      equivalent barrier speed are frequently used parameters. These parameters are
      most often estimated from vehicle deformation. It is known, however, that the
      quality of these estimates is limited if compared with these obtained in
      laboratory test conditions. To be able to achieve almost the same measurements
      and measurement accuracy in real-life accidents as in the laboratory, where the
      acceleration time history is measured, an on-board measurement technique is
      required. This presentation gives results of tests of a low cost device for
      measuring the crash pulse for a car involved in an accident, concerning
      systematic and random error. The device, called the Crash Pulse Recorder (CPR),
      has been tested previously in several sled tests. The CPR is based on measurement
      of the movement of the mass in a spring mass system in a collision. A brief
      description of its construction is also included. The CPR is an integral part of
      a large accident data collection system including interior and exterior
      deformation measurements and evaluation of injury outcome. This report presents
      the results of several full-scale crash tests, undertaken to evaluate the
      accuracy and precision of the CPR in cars in different impact modes. The tests
      comprised both offset and angled collisions. Most of the tests were car to car
      collisions, but barrier tests were also performed. The random error of the CPR
      was found to be 2.2 km/hr for the delta V measurements and 0.6 g for mean
      acceleration.

PMID- 8579703
TI  - Pedestrian exposure to risk of road accident in New Zealand.
AB  - This study uses data from a recent survey of New Zealanders' travel behaviour to
      estimate the pedestrian risk of road accident injury. The estimated risks of
      accident disaggregated by sex and age were examined by combining road accident
      data with survey data using the exposure measures "time spent walking" and
      "number of roads crossed". The two resulting measures of risk were compared both
      with one another and with the most common mode of presenting of pedestrian
      accident statistics, accidents per capita. The overrepresentation of the elderly
      in pedestrian accident statistics was examined in light of their greater
      susceptibility to injury from a given accident. An attempt was made to adjust for
      this susceptibility using estimated numbers of "severe impacts" based on the risk
      of road accident fatality per road crossed. The relative importance of walking as
      a mode of transport was examined using the travel survey data. Finally, the risks
      of road accident when crossing at a zebra (unsignalized) crossing were compared
      with the risks of crossing elsewhere.

PMID- 8579704
TI  - [The City and Health--an analysis of recent (socio-) historical literature].
AB  - "The City and Health" - this title joints two all-encompassing words. The city is
      the birthplace of modern civilization. Today, we are confronted with huge urban
      agglomarations--beyond our grasp and nearly out of control. Are we dealing with
      transitory phenomena, such as the filthy and inhuman cities of the early
      industrial era seem from the historical point of view? This is our hope. Here
      inevitably, we strike upon the term "Health". For in the endeavor to create in a
      city first permanent and then "proper" conditions and finally to achieve proper
      behaviour, health became a central term. Today, to be healthy is our most
      heartfelt desire. Still, we do nor know what health is. The theme "City and
      Health" is therefore significant, historically as well as at present. So a brief
      historical survey will illustrate a few elements characteristic of the
      interrelationship of health and the city from the civilizational point of view (
      = 1.). To determine the historical point of our inquiry, we will then outline the
      recent discussion on urban history ( = 2.). Upon this ground, we shall discuss
      cities as a special expression of community, the sciences of health as a special
      type of medicine, and the modern industrial living conditions with regard to the
      recent socio-historical and medico-historical literature published since 1980 ( =
      3.).

PMID- 8579705
TI  - [Infectious diseases from the hygienic viewpoint with special reference to
      environmental infections--a retrospective and prospective view].
AB  - Infectious diseases showed a considerable change in their epidemiologic
      significance during this century. Twenty years ago it seemed that infectious
      diseases would be definity under control. As a result there was a neglect of the
      efforts for prevention, recognition and controlling of infectious diseases,
      especially in the administration. Today we have to state that old and new
      infectious diseases have regained a new and partly dramatic epidemiologic
      importance, influenced by several factors like overpopulation, wars, hunger,
      migration in the underdeveloped countries and the increase of the old and the
      immunosuppressed people of the population in the developed countries. A review is
      given of the increasing significance of old and new infectious diseases in the
      last 2 decades. Transmissible diseases from the environment have a special
      importance because many people are affected hereby. Hygienic aspects of drinking
      and swimming water, air- and ground caused infectious diseases are treated. The
      political support is requested. The institutions have had an important role in
      the prevention and control of infectious diseases in the past like the public
      health departments, hygiene and medical microbiologic urgently need the support
      and promotion of the government.

PMID- 8579706
TI  - [Toxic compounds in our environment--challenge or cost of prosperity].
AB  - The goal of this contribution was the description of the possibilities as well as
      the limitations to which a toxicologist is confronted when evaluating potential
      toxic compounds to which human beings can be exposed during their lifetime. The
      number of substances is overwhelming. The available methods for the evaluation
      are not satisfactory for everybody. Nevertheless, the results are not as bad as
      sometimes is asserted: in the industrial societies, the expected life span of men
      increases. The evaluation of the effects is unsatisfactory especially for the
      carcinogenic and allergic potential of foreign compounds. This is the consequence
      of our limited knowledge about the biological processes underlaying these
      effects, or, in other words, research must be intensified in this field. Finally,
      the experiences of the public as well as of the media with risks and their
      evaluation are not satisfactorily developed. The intellectual development of the
      public is rather slow compared to that in business life and economics. This means
      that everybody oughts to acquire knowledge in order to be able to make
      appropriate decisions in a world increasingly complicated. Otherwise, our society
      ends up with a convenient home for the aged combined with a cemetery. And this,
      by the way, is less than a recreation center (Freizeitpark).

PMID- 8579707
TI  - [Strategies for evaluating carcinogenic substances].
AB  - Cancer from exposure to chemicals is known for more than two centuries. Today,
      approximately 40 compounds have been identified as unequivocally carcinogenic in
      humans, more than 300 have been shown to be carcinogenic in animal
      experimentation. Accordingly, an old system subdivides carcinogens as human
      carcinogens (A1), animal carcinogens (A2, and compounds being suspective of
      exerting carcinogenic activity. There exist no threshoulds of effect for
      notorious carcinogens. In order to improve the protection of those exposed to
      carcinogens in the working area, a special type of tolerance values has been
      introduced (technical guidance values, TRK). Contrary to MAK-values, these TRKs
      take into account a certain residual cancer risk which in most cases can not be
      quantified. The amount of acceptable residual risks is a matter of political
      consensus which has to be organized between the societal groups involved. For the
      purpose of quantitative comparisons, "unit risks" have been introduced; the
      problematics of this category is discussed to some extend.

PMID- 8579708
TI  - [Epidemiological risk assessment for chemical substances].
AB  - Epidemiological risk assessment for chemicals is usually based on analytical
      studies like case-control or cohort studies. Both study types have a number of
      specific advantages and disadvantages which are outlined. The evaluation of a
      substance is done on the basis of the results of these studies either
      qualitatively or quantitatively. For quantitative risk assessment reliable data
      are needed for the dose of the substance to which the individuals in the study
      were exposed. For a number of chemical sufficient data are available. Among these
      are experimental pollutants like arsenic, benzene or radon. As an example the
      possibilities of risk assessment for dioxin are outlined. The knowledge on the
      carcinogenicity of dioxin has significantly improved during the last years. Some
      research groups currently use data of a number of cohort studies to perform a
      quantitative risk assessment.

PMID- 8579709
TI  - [Allergic diseases in the indoor environment].
AB  - Allergic diseases have severely increased worldwide through the last 30 years.
      More than 50% of all allergic diseases are caused by allergens out of the indoor
      environment. The most important allergen-carriers are cats, mites and molds.
      Since the first energy-crisis in 1970 private houses and offices had to be saved
      from energy losts, which decreased the rate of air changing and increased the
      relative humidity in the indoor environment. The hygienic situation of air
      conditioning systems is often insufficient controlled and leads to
      microbiological contamination. In Germany the number of cats, kept in private
      homes has increased significantly. These are important facts which led to an
      increase of indoor air allergies. The greatest number of mites and mold allergens
      are to be found in mattresses and textile furnitures. For most of the allergens
      in indoor air the correlation between the sensitizing allergen concentration and
      onset of illness is unknown. Diagnostic and therapy of allergies in the indoor
      environment must be supported by prevention and eliminating the main sources of
      allergen exposure.

PMID- 8579710
TI  - [Experiences with an ambulance for environmental medicine at the Hygiene
      Institute of the Heidelberg Universy Hospital].
AB  - Outpatient department and advice centres for environmental medicine were
      established in the late eighties in Germany. Most of these institutions focus on
      patient-care, whereas scientific questions have only been dealt with randomely.
      Thus the evaluation of applied methods and procedures is not satisfactory at
      present. Patients suffering from "environmental-medical" disorders usually
      complain about chronic or recurring illnesses. Up to now the complex etiology has
      not been understood. Generally environment agents in a literal sense do not seem
      to be of great importance. It is merely impossible to verify the extent to which
      such exposures influences a multifactorial etiology. Acute health disorders or a
      disorder that can definitely be related to a specific cause occur very rarely in
      our field. Thus a serious methodological dilemma results for the clinical aspect
      of environmental medicine. Nevertheless an increasing number of patients
      associate their complaints to environmental influences such as harmful substances
      and physical environmental influences, e.g. electromagnetic fields. Mass media
      and some physicians support is idea. Scientifically unsound methods of treatment
      are often applied to "Environmental practices", "Environmental clinics", "Mobile
      Environmental Outstations", The results of diagnostic examinations are
      interpreted in a dubious fashion and questionable therapeutic advice is given. An
      extension of the environmental medical field is not only taking place in the
      private (commercial) sector; but public institutions, especially public health
      centres, are participating in the unreflected extension of the outpatient section
      for environmental medicine. As a consequence we decided to establish a research
      oriented "Environmental Outpatient Department" as part of the Hygiene Institute
      of the Heidelberg University in 1993. The aim was an evaluation of the concept of
      outpatient stations and if required its further development. The main aspects of
      the Heidelberg outpatient station-concept will be shown as well as the first case
      related research results which have reinforced our critical attitude towards
      clinical environmental medicine. In less than a tenth of the presented cases
      environmental agents could be proved partly responsible for the mentioned
      complaints. In a third of all cases a connection between the suspected
      environmentally harmful substances or others and the apparent health disorders
      could neither be proved nor totally denied. There was, however, little evidence
      for a causal connection. In two-thirds of the cases physical-chemical
      environmental pollution could not be proved responsible for the complaints. More
      than half of the patients suffered from more or less obvious psychosomatic
      problems.

PMID- 8579711
TI  - [Risk assessment of microorganisms relevant to food hygiene].
AB  - In the public's view, chemical residues still dominate in the ranking of
      foodborne hazards. This perception is changing slowly as a result of public
      discussions on the dangers to human beings from various microorganisms in
      foodstuff. Statistics on foodborne infections and intoxications comprising acute
      diseases have shown that chemical substances (including fungal toxins) play a
      less significant role than bacteria. A sentinel and a populations study from
      Holland provides information on the incidence of cases of acute gastroenteritis
      caused by microorganisms in foods. The results of this study show that 100 to 150
      cases are to be expected annually per 1000 inhabitants. An economic cost of about
      $1000 per case of disease is calculated in Canada and the USA. On the basis of
      these figures and the Dutch study, the estimated annual economic impact is more
      than 10 billion DM for the Federal Republic of Germany. The difficulties in
      quantification of microbiological hazards from foodstuffs on the base of dose
      response relation and exposure assessment such as are usual in the risk
      assessment of chemical hazards are discussed. A safety concept of the food
      industry (the HACCP concept) is then described. This comprises hazard
      identification. risk assessment as well as risk management. This concept is also
      applicable in other food areas such as communal catering. In the meantime, it has
      also been taken into consideration in European food legislation.

PMID- 8579712
TI  - [Epidemiology of microbial resistance to biocides].
AB  - In order to estimate the distribution of bacteria and fungi with an elevated
      level of resistance to antimicrobial substances, we have analyzed water samples
      and surveyed institutions presumably concerned with analyses of microbial
      resistance (university institutes for hygiene, health authorities) by means of
      questionnaire. A total of 41 water samples was drawn from various aquatic
      biotopes in the region of Heidelberg. The samples originated from the effluents
      of a community sewage treatment plant, from the Neckar river, from drinking water
      supplies and from public swimming pools. The following substance groups were
      included in a search for bacteria with an elevated resistance to antiseptics and
      disinfectants: Aldehydes, biguanides, quaternary ammonium compounds (QAC),
      phenols and halogen. Upon determination of the maximal tolerated concentrations
      to these antimicrobial agents, samples of treated wastewater effluents showed a
      considerably higher prevalence of bacteria resistant to formaldehyde,
      chlorhexidine and QAC. The highest levels of resistance were found in Pseudomonas
      aeruginosa, Pseudomonas putida, Pseudomonas fluorescens and Enterobacter species.
      The maximal tolerated level of 0.06 percent formaldehyde by weight was
      considerably higher than the levels tolerated by the corresponding ATCC reference
      strains. The highest levels of resistance to a biguanid/QAC preparation were seen
      in isolates of Alcaligenes species and Providencia species, with a maximal
      tolerated level of 0.5 volume percent. In addition, several isolates of E. coli
      and Klebsiella species were observed which showed a considerably higher level of
      resistance to the biguanide preparation as compared to the corresponding ATCC
      reference strains. A questionnaire was mailed to a series of institutions and
      companies presumably concerned with problems of microbial resistance. Responses
      were in accordance with our own observations, both with regard to the spectrum of
      bacteria observed and to the antimicrobial substances concerned.

PMID- 8579713
TI  - [Epidemiology and reasons for microbial resistance to biocides].
AB  - In the last years the significance of microbial resistance to biocides like toxic
      heavy metal ions, aldehydes, phenoles, and cationic surface active agents has
      increased. However the genetical and functional mechanisms of the resistance to
      most of these compounds are still unknown. Till now it was possible to
      demonstrate a plasmid resistance in only some bacterial strains which were
      resistant to heavy metal ions, hexachlorophene, formaldehyde,
      benzalkoniumchloride, and chlorhexidine. In mercuric resistant Staphylococcus
      aureus and formaldehyde resistant E. coli strains the resistance genes are now
      well characterized. These strains are able to produce enzymes which degradade the
      disinfectant. The resistance to cationic surface active agents seems to depend on
      a modification of the bacterial cell wall. This is concluded from former
      investigations with benzalkoniumchloride resistant Pseudomonas strains, where it
      was possible to demonstrate different lipid contents in the cell wall from
      resistant and sensitive strains.

PMID- 8579714
TI  - [Hygienic aspects with regard to nursing of home care patients with AIDS, chronic
      diseases and mental handicaps].
AB  - A human handicap is defined as a broad, hard and long lasting restriction of the
      mental development and the social integration. Groups of handicapped persons can
      be divided into mentally, psychologically, physically, sensory (blind, deaf)
      handicapped as well as into multiple disabled and chronically sick persons and
      those in need of care (old). New groups with demands for aid are among others
      people suffering from AIDS, psychologically sick (old) and people getting old as
      well as mentally, physically und multiple handicapped persons, people suffering
      from cancer, severely ill and dying people. For all handicapped people should be
      demanded the possibility of living almost normal lives. For all persons directly
      concerned as well as their families such a normal life should include: the right
      of self-determination and autonomy, the demand for complex styles of living and
      nearby care/support, the providing of respective infrastructures such as barrier
      free living and access to public institutions, access to public transport and
      homes fitting for handicapped persons, the demand for out-patient treatment by a
      complex range of various possibilities of support and finally, the providing of
      alternative forms of living in contrast to the traditional way of life of
      handicapped people like families or homes. Three important living areas can be
      derived from these ideas, namely: living conditions, education/professional and
      working field, social life/social environment. These important living areas
      require preventive measures, mainly advice and information centres, places to go
      early recognition and early promotion of handicapped people and those in risk of
      a handicap (especially children) as well as medical, professional and social
      rehabilitation or integration. Concerning the spectrum of support, aid and care
      in the homely area up to now already exists a variety of offers by out-patient
      services (information services, social units, mobile support services/organized
      neighbourhood assistance, individual care of severely sick persons, food
      services, laundry services, social psychiatric services for chronic mentally sick
      persons, cancer advice/care, hospital aid, care of persons suffering from AIDS,
      family relieving services for family members of mentally disabled persons,
      supervised living) partial treatment of indoor-patients such as daily care units,
      daily nursing or daily clinics others like nursing families, living communities,
      short-time care/accommodation, homes for sick people. Moving forces of these
      offers are mainly charitable organizations such as organisation of social welfare
      and churches. Besides, aid for handicapped people is also realized by state and
      local community authorities (Social Welfare and Public Health Department) and
      private initiatives. In spite of these offers there exist numerous problems und
      gaps. With regard to the problems one should mention predominantly the financing
      of measures, specific problems concerning the home care of persons (among others,
      asking for help too late, less preventive orientation of the services, low
      orientation of the services with regard to the needs of the handicapped persons
      and their families, few coordination or cooperation among the services, nursing
      crisis, few persons engaged in community services) as well as problems in the
      field of living and living environment (non existence of handicapped-fit or
      specially furnished homes, lacking infrastructure, public transport not
      sufficiently equipped for handicapped people, practices of physicians, pharmacies
      or shops not accessible for handicapped persons). Gaps in the offers are among
      others the long-time care, crisis intervention/emergencies particularly for
      singles as well as the nursing possibilities of partial treatment.

PMID- 8579715
TI  - [Irrationality and risk--a problem analysis].
AB  - The way one experiences risks and one's risk behaviour is not centrally the
      result of rational considerations and decisions. Contradictions and
      incompatibilities can be proved empirically: (1) General paranoiac hysterical
      fear of risks, (2) complete repression of health risks, (3) unsureness and
      inability in dealing with risks, (4) prejudice against risks, (5) admiring risk
      behaviour, (6) seeking dangerous ways to test one's own limits, (7) readiness for
      aggression by not subjectively being able to control the risk, (8) naively
      assessing a risk positively thus intensifying pleasurable sensation, (9)
      increased preparedness to take risks in groups, (10) increased preparedness to
      take risk in anonymity, (11) accepting risks as a creative challenge for
      achievement motivation, (12) loss of innovation when avoiding risks. The
      awareness and assessment of risk factors is dependent on (1) personality factors
      (achievement-motivated persons experience risk as a creative challenge; risk
      behaviour being a variation in stimulus and exploration of one's environment),
      (2) the social back-ground (booster function), (3) the culture-related assessment
      of being able to control risks and (4) age (youthful risk behaviour being a way
      of coping with developmental exercises, e.g. purposely breaking parent's rules,
      provocatively demonstrating adult behaviour, a means to solve frustrating
      performance failures, advantages through social acceptance). The way one copes
      with risk factors is based on subjective estimation of risk; this assessment is
      made anew for each area of behaviour according to the specific situation. Making
      a decision and acting upon it is the result of simultaneously assessing the
      possible psychological benefit-cost factors of taking risks. The extent, to which
      the threat of risk factors is felt, depends on the importance one attaches to
      certain needs and benefits of quality of life and, in addition to this, what the
      subjective probabilities are that one is likely to be befallen by a particular
      risk; here it is possible that the subjective likelihoods of the risk occurring
      are maximized and minimized (e.g. hygiene, immunizations risks). The subjective
      risk hierarchies--they are often contrary to scientific knowledge--are additional
      evaluation factors.

PMID- 8579716
TI  - [Psychology of nursing personnel in home care nursing].
AB  - In a random survey questions were put to 100 employees of home care centers (51
      qualified nursing staff, 28 assistants and/or trainees, 21 young people doing
      community service as an alternative to military service). MAIN RESULTS: (1) The
      job motivation is primarily of a private nature: social commitment, achievement
      motivation, being responsible for solving diverse human problems are at the
      centre of job orientation. (2) Huge disappointments (neglect of patients, stress,
      arrangement of working hours, bureaucracy, lack of self-responsibility) are in
      62% of the cases the reasons for changing from a clinic to the home care centre.
      (3) The psychological results of home care nursing are only positive in 62% of
      the cases; 26% have thought of giving notice, 37% would not choose their job
      again. (4) The training qualification for home care nursing is only adequate for
      60% of those questioned; deficiencies are experienced with regard to consulting
      competence, gerontopsychiatry, specific knowledge about illnesses, legal
      questions. Essential further training is neglected. Also initial instruction in
      the home care service is to a great extent unsatisfactory. (5) For economic
      reasons it is frequently necessary to limit daily care to basic nursing; the
      patients' communicative needs have to ignored. One's occupational self-importance
      dwindles away; the job increasingly becomes an everyday stress factor. (6) The
      high risk of infection in the case of home-care patients is considered to be
      above-average (bedsores, infection risks with regard to changing
      bandages/catheters, anuspraeter aids, incontinence, fungal diseases, food risks:
      not keeping to diets, food not suitable for the elderly, lack of appropriate
      storage for leftovers. (7) Nursing staff, as well as patients, regard soap,
      cleansing lotion, shampoo, tooth brushes and toothpaste as the main items for
      personal hygiene, for the prevention and treatment of bedsores. Beyond that,
      compared with nursing staff, patients have a greater need for personal hygiene
      products (deodorants, mouthwash, perfume, etc.): personal hygiene providing
      mental stimulation. (8) Doctors are not integrated sufficiently into the social
      network of nursing home-care patients. The required quality of cooperation with
      the nursing staff only exists in part. (9) Contact to the overworked relatives is
      generally positive. Cooperation can be optimized by imparting basic nursing
      knowledge, by getting the relatives to participate in one's own work, by
      enlisting the home-care centre early on and through psychological support by
      third parties (e.g. discussion courses).

PMID- 8579717
TI  - [Toxicology and environment as regards their positions in society. Recognizing
      health risks to humans].
AB  - The nature of hazard identification and risk assessment for human health of
      chemicals in the environment are examined. Sources of uncertainty in the
      experimental approach to defining toxic hazards and risks are described and so
      are factors that limit the quality of many epidemiological studies of population
      toxicity. It is important for the toxicologist to consider all forms of risk both
      as probabilities and in terms of the nature and severity of the harm done to
      those affected. Toxicology, especially in its application to man and
      environmental hazards, may be influenced by societal and other politico-economic
      factors. Toxicologists must take care, therefore, to be recognised as true
      professionals, by recognising their obligations both to the proximate user of
      their results ad their wider responsibilities to society.

PMID- 8579718
TI  - [Family situation of home care givers].
AB  - 80 family care givers were interviewed. Half of them were daughters or daughters
      in-law of the patients, half were parents and partners. 30 of them were supported
      in care giving by professionals. Half of the patients were younger, half were
      older than 70 years. Results of the study can be summarized as follows. The days
      of family care givers are packed with care giving activities, there is little
      spare time. Daily hassles keep increasing without hope that the situation will
      improve. Often, a radical change in life style becomes necessary when, all of a
      sudden, care giving is needed. Families are met unprepared, and thus, there is a
      deficit in competencies, resulting in insecurity, embarrassing situations, and
      overwork. Although they know that hygiene is crucial for the elderly and sick,
      and they know about the importance of care of the body for the patients' well
      being, hygiene deficits are found which are due to care givers' overwork. Most of
      the time, meals are freshly prepared by care givers. Anyway, keeping and
      reheating meals and not being watchful enough as far as mold is concerned results
      in health risks for the elderly and sick. Care givers supported by professionals
      rate their aid positively. Problems are generally due to time mismanagement.
      Nursing homes are rejected and morally condemned by care givers and patients
      unanimously. Only a few care givers feel so overworked that they would prefer
      nursing home care.

PMID- 8579719
TI  - [Realization and financing of different models of home care].
AB  - In the long term perspectives for home care are characterized by four challenges:
      First, home care services can be rationalized only below average. If
      professionals in the home care services shall take part nevertheless in the
      general development of wages in the economy, it is necessary that a rising part
      of domestic income will be spent for these services. Second, in the families
      tensions between the desire for self-realization of the middle generations and
      expectations of home care patients that the next generation shall take over
      caring responsibilities, will increase, which will lead to a rising demand for
      professional home care services. Third, the rising proportion of single
      households will also lead to a rising demand for professional services, because
      people living alone need more services than people living within families.
      Fourth, the future demographic development will not only lead to a rising number
      of people in need of home care but also to declining number of younger people.
      This will cause not only problems for financing of welfare state programs for
      people in need of home care but will also lead to a scarcity of nursing
      professionals. Against this background the new "Social Long Term Care Insurance,"
      which will come into effect in Germany by 1995 has to be examined for its
      economic justifiability, for its distributional justice and for the effectiveness
      of its benefits. The new insurance program can strengthen home care; however in
      terms of economic justifiability and distributional justice it is not without
      risks.

PMID- 8579720
TI  - Autoantibodies to glutamic acid decarboxylase in patients with autoimmune thyroid
      disease: relation to competitive insulin autoantibodies.
AB  - We evaluated the presence of autoantibodies to glutamic acid decarboxylase (GAD),
      competitive insulin autoantibodies (IAA) and islet cell antibodies (ICA) in sera
      from 288 non-diabetic patients with autoimmune thyroid disease (AITD), including
      212 patients with Graves' disease and 76 with Hashimoto's thyroiditis, and in 235
      age- and sex-matched healthy control subjects. GAD antibodies and IAA were
      assayed using radioimmunoassay with 125I-labelled purified pig brain GAD and
      human insulin, respectively. Titers of greater than 4.7 units for GAD antibodies
      and 50 nU/ml for IAA, respectively, the mean + 3SD of 235 age- and sex-matched
      healthy individuals, were defined as positive. The mean titers of GAD antibodies
      in patients with Graves' disease and in patients with Hashimoto's thyroiditis
      were 3.6 +/- 4.6 (mean +/- SD, range 0.6-52.0) units and 3.2 +/- 1.4 (range 0.6
      10.0) units, respectively. Titer of GAD antibodies in patients with AITD was
      significantly higher than in healthy controls (P < 0.0005). Thirteen of 212
      (6.1%) patients with Graves' disease and 6 of 76 (7.9%) patients with Hashimoto's
      thyroiditis had positive GAD antibody titers, whereas titers in healthy control
      sera were < 4.7 units in all but two individuals (P < 0.005). In competition
      analysis with purified unlabelled GAD, binding tracer was inhibited in all of 13
      GAD antibody-positive Graves' sera and 5 of 6 GAD antibody-positive sera from
      patients with Hashimoto's thyroiditis. Eight of 212 (3.8%) patients with Graves'
      disease and 3 of 76 (3.9%) patients with Hashimoto's thyroiditis, but none of
      healthy controls had IAA levels exceeding the range for normal controls (P <
      0.005). Positive IAA levels ranged between 50 and 2383 nU/ml. Strikingly, all of
      19 GAD antibody-positive sera were negative for IAA. ICA were not detected in any
      of the patients or healthy controls. These data demonstrate that GAD antibodies
      in sera of AITD patients are of low titer but significantly elevated compared to
      healthy controls, and are independent of the appearance of IAA. They also
      indicate that, in patients with AITD, an autoimmune response to GAD may occur
      with no relationship to production of IAA.

PMID- 8579721
TI  - HLA-associated heterogeneity of the humoral response to islet antigens in insulin
      dependent diabetes.
AB  - Insulin-dependent diabetes mellitus (IDDM) is associated with susceptibility HLA
      class II alleles. Islet cell antibodies (ICA), detected by indirect
      immunofluorescence on pancreas sections, represent the best marker of the
      disease. Autoantibodies to glutamic acid decarboxylase (GADA), one major islet
      antigen, do not totally account for ICA reactivity, suggesting heterogeneity of
      the anti-islet humoral response. In 97 patients with IDDM we have correlated ICA
      heterogeneity with clinical markers and DR and DQ alleles. ICA were found in 81%
      of the patients, and in 33% the serum blocked the binding to islet cells of
      reference sera with a granular fluorescence pattern. GADA were found in 62% of
      cases. Patients with high GADA titers and blocking sera were older at onset and
      less often had a family history of IDDM, suggesting that these antibodies might
      be a marker of slow progression to IDDM. ICAs were not associated with particular
      HLA DR or DQ alleles. Conversely, GADA were less frequent than ICA in DR4
      subjects but not in the other groups. Moreover, among DR4 non-DR3 patients, GADA
      were found almost exclusively in DRB1*0401 patients but not in other DR4
      subtypes. There was an association of GADA with DQ alleles but it was secondary
      to linkage disequilibrium between DR and DQ loci. In conclusion, the
      heterogeneity of the humoral response in IDDM is controlled by HLA class II genes
      and correlates with clinical heterogeneity.

PMID- 8579722
TI  - Purification of recombinant human Hsp60: use of a GroEL-free preparation to
      assess autoimmunity in rheumatoid arthritis.
AB  - A 65 kDa mycobacterial heat shock protein has been implicated in the development
      or perpetuation of the inflammatory diseases rheumatoid arthritis (RA) and
      insulin dependent diabetes mellitus (IDDM). An homology of the mycobacterial
      hsp65 with human hsp60 (HuHsp60) has been thought to constitute a cross reactive
      autoimmunizing pathogenetic potential. Study of this cross reactivity with
      recombinant reagents has been complicated by the fact that recombinant HuHsp60
      might be contaminated by the E. coli homologue of HuHsp60, groEL. GroEL and
      HuHsp60 are very similar in isoelectric point and molecular weight and therefore
      difficult to separate by classical physicochemical means. Therefore, the HuHsp60
      gene was subcloned into the vector, pRSET-B, which resulted in recombinant
      HuHsp60 protein fused to a 4.5 kDa peptide containing a polyhistidine hexamer.
      Metal ion affinity for the polyhistidine allowed the rapid and efficient
      chromatographic separation of the HuHsp60 from groEI. Rabbit antisera were
      developed to linear peptide epitopes unique to either HuHsp60 or groEL and
      utilized to discriminate between these proteins during their separation. With the
      newly prepared HuHsp60 we show that the amount of anti-HuHsp60 autoantibody in
      both RA and normal sera was too great to be accounted for by cross reacting anti
      MbHsp65.

PMID- 8579723
TI  - Significantly increased maternal and fetal IgG autoantibody levels to 52 kD Ro
      (SS-A) and La(SS-B) in complete congenital heart block.
AB  - Antibodies to Ro(SS-A) are an important laboratory parameter of congenital heart
      block (CHB), but the maternal presence of anti-Ro(SS-A) antibodies does not
      always lead to this fetal acquired autoimmune disease. The current study
      investigated quantitative and qualitative differences of anti-52, -60 kD Ro(SS
      A), 0La(SS-B) and -U1RNP(-C, -A, -68 kD) autoantibodies (either IgG or IgM) in
      sera derived from 16 infants with CHB and their mothers compared to eight healthy
      anti-Ro(SS-A) positive infants (controls) born to SLE mothers. No serum sample
      contained IgM auto-antibodies of the specificities investigated. Anti-60, 52 kD
      Ro(SS-A) and La(SS-B) IgG antibodies coincided in 9/16 CHB cases, exclusively (P
      < 0.05). Associated anti-52 kD Ro(SS-A) and -La(SS-B) IgG antibodies were
      detected in 14/16 CHB and in 3/8 control cases (P < 0.05). Anti-U1RNP 68 kD
      antibodies occurred in 1/16 CHB infants and in 4/8 controls. In general, newborn
      and maternal antibody patterns and reactivities were similar in all cases
      investigated. The fetal CHB sera contained significantly higher IgG levels of
      anti-52 kD Ro(SS-A) (P < 0.005) and -La(S-B) (P < 0.015) compared to control
      samples. Sera from mothers with CHB children had significantly higher levels of
      anti-52 kD Ro(SS-A) (P < 0.015) and -La(SS-B) (P < 0.015) IgG antibodies than
      those of the control group. Thus, the coincidence of anti-52 kD, -60 kD Ro(SS-A)
      and -La(SS-B) IgG antibodies as well as significantly increased levels of
      antibodies to 52 kD Ro(SS-A) and La(SS-B) are associated with evidence of
      complete congenital heart block. The data suggest that the known associated
      humoral autoimmune findings are exclusively of maternal origin.

PMID- 8579724
TI  - TSH receptor sequences recognized by CD4+ T cells in Graves' disease patients and
      healthy controls.
AB  - Twenty-nine overlapping synthetic peptides, twenty residues long, representing
      the entire extracellular sequence of the human thyroid stimulating hormone
      receptor (hTSHr), were used to test the epitope repertoire of CD4+ T lymphocytes
      from patients with Graves' disease and from healthy subjects. The peptides were
      used to propagate and test short term CD4+ T cell lines specific for hTSHr
      epitopes, and to directly test CD8+ depleted, CD4+ enriched peripheral blood
      lymphocytes. Analysis of the response of short-term CD4+ T cells lines and CD8+
      depleted peripheral blood lymphocytes to the individual peptides revealed that 14
      of the 15 patients and nine of the ten controls responded to at least one hTSHr
      peptide. There was no common response pattern, nor any region of the hTSHr
      sequence that was predominantly recognized. Several peptides were recognized by
      both patients and controls. These results support the notion that immunological
      tolerance to hTSHr is due to peripheral tolerance of potentially autoreactive
      CD4+ T cells, not their clonal deletion. The presence of self-reactive, hTSHr
      specific CD4+ T cells in healthy individuals implies that these cells are not
      permanently anergized, since they can be activated in vitro.

PMID- 8579725
TI  - Cytoplasmic accumulation of the 52 kDa Ro/SS-A nuclear autoantigen in transfected
      cell lines.
AB  - The 60 kDa Ro/SS-A (Ro60) autoantigen is thought to reside predominantly in the
      nucleus; however, the intracellular localization of 52 kDa Ro/SS-A (Ro52) in
      normal cells is controversial, probably due to its low abundance. Therefore, we
      studied the intracellular expression and localization of the human Ro52 following
      transfection of a human Ro52 cDNA into cultured cell lines. Immunofluorescence
      staining of human (HEp-2) and mouse (LTA-5) cell transfectants with affinity
      purified anti-Ro52 antibodies revealed that Ro52 antigen was most abundant in the
      cytoplasm and present to a lesser extent in the nucleus. This relative
      localization was supported by a preponderance of the Ro52 antigen in the
      cytoplasmic rather than nuclear fraction of enucleated cell lines detected by
      immunoblotting. In contrast to the Ro52 autoantigen, Ro60 and La autoantigens
      were mainly expressed in the nucleus of transfected cells under similar
      circumstances, indicating distinct localization of the intracellular pools of
      these autoantigens. The findings indicate that the Ro52 autoantigen lacks
      intrinsic signals required for nuclear localization and suggest that a
      significant pool of this autoantigen resides in the cytoplasm. Ro52 may therefore
      rely upon an association with other molecules for any specific nuclear transport.

PMID- 8579726
TI  - Anti-oxidized LDL antibodies and antiphospholipid antibodies in healthy subjects:
      relationship with lipoprotein- and oxidation-related analytes.
AB  - IgG autoantibodies against malondialdehyde-modified LDL (alpha oxLDL),
      antiphospholipid antibodies (APA) and oxidation- and lipoprotein-related analytes
      were assayed in sera from healthy subjects (51 males, 115 females, aged 22-63
      years). alpha OxLDL levels were associated (P < 0.03) with IgG alpha cardiolipin
      (r = 0.18), IgM alpha cardiolipin (r = 0.17) and IgM alpha phosphatidyl-serine (r
      = 0.16) but not with age, cholesterol, triglyceride, apolipoproteins B and AI,
      lipoprotein(a), lipid peroxides, ceruloplasmin, copper, ferritin, transferrin or
      iron. APA levels were inversely associated with levels of both oxidation- and
      lipoprotein-related analytes. Ferritin (3.5%) and alpha oxLDL (1.4%) contributed
      independently to variation in IgG alpha cardiolipin levels, and apo B (2%) to
      variation in IgM alpha cardiolipin levels. These associations are small,
      indicating that there are no major biological associations between the measured
      variables. The lack of association between alpha oxLDL and lipoprotein- or
      oxidation-related analytes suggests that the relevant antigen is not in serum.

PMID- 8579727
TI  - 2-Buten-4-olide (2-B4O) inhibits experimental allergic encephalomyelitis (EAE) in
      Lewis rats.
AB  - Starvation is well known to induce immune suppression. Moreover, the
      concentration of 2-B4O, an endogenous sugar acid, is elevated in the circulation
      during starvation. To determine if these events are related, the influence of 2
      B4O on experimental allergic encephalomyelitis (EAE) in Lewis rats, a model of
      human multiple sclerosis (MS), was studied. EAE, characterized by paralysis of
      hind legs, was induced by immunization with residues 68 to 84 (MB 68-84) of the
      guinea pig myelin basic protein (MBP) in complete adjuvant H37Ra. Interestingly,
      the daily administration of 2-B4O intraperitoneally from the day of MB 68-84
      immunization (day 0) to day 20 dramatically suppressed the clinical severity of
      EAE. The daily administration of 2-B4O intraperitoneally from day 0 to day 7 also
      markedly reduced the clinical symptoms of EAE. In fact, passively induced EAE,
      using Con A activated spleen cells from rats immunized with MB 68-84 in H37Ra,
      was also inhibited by daily administration of 2-B4O. Histological examination
      confirmed clinical findings and revealed that mononuclear cell infiltration into
      the central nervous system was significantly inhibited by 2-B4O. To clarify the
      mechanism(s) responsible for suppression of EAE, the effects of 2-B4O on the
      immune responses to MB 68-84 were examined. When rats were treated daily with 2
      B4O for 15 days after immunization with MB 68-84 in H37Ra, the delayed-type
      hypersensitivity (DTH) response to MB 68-84 was significantly reduced in 2-B4O
      treated rats as compared with saline treated rats. The proliferative response to
      MB 68-84 of spleen cells from 2-B4O treated rats was also significantly lower
      than that of saline treated rats. Our data demonstrate that 2-B4O has the
      potential to suppress autoimmune responses in both inductive and effector phases.
      2-B4O may have significant potential to treat autoimmune diseases.

PMID- 8579728
TI  - Differential effects of polysulfated polysaccharide on experimental
      encephalomyelitis, proliferation of autoimmune T cells, and inhibition of
      heparanase activity.
AB  - The extravasation of activated T lymphocytes through blood vessel walls and their
      migration to inflammatory loci are associated with secretion of extracellular
      matrix (ECM)-degrading enzymes, such as heparanase, which degrades heparan
      sulfate (HS) moieties of the ECM. The HS-degrading activity of heparanase was
      found to be inhibited by HS and heparin. Since induction of experimental
      autoimmune encephalomyelitis (EAE) requires extravasation and migration of
      autoimmune T cells, degradation of ECM by heparanase is expected to be involved
      in induction of the disease. Herein, we examined whether laminarin sulfate, a
      polysulfated polysaccharide (PSS) isolated from the cell walls of seaweeds and
      subjected to chemical sulfation, could inhibit ECM degradation by mammalian
      heparanase, and could prevent EAE. PSS was a more potent inhibitor of heparanase
      mediated degradation of ECM than heparin. In-vivo, PSS, injected once a week,
      inhibited the severity of actively-induced EAE in rats. However, inhibition of
      EAE was not due to an overall suppression of autoimmune T cells, since PSS
      enhanced the proliferation of myelin basic protein (MBP)-specific,
      encephalitogenic T cells. PSS-activated autoimmune T cells, but not MBP-activated
      cells, failed to induce EAE in recipient rats. Moreover, rats injected with PSS
      activated T cells were resistant to induction of EAE by anti-MBP CD4+ T cells.
      Thus, PSS may have potential clinical applications in the treatment of autoimmune
      diseases.

PMID- 8579729
TI  - Induction of type II collagen arthritis in the DA rat using silicone gels and
      oils as adjuvant.
AB  - The relative safety (or otherwise) of silicone gel filled breast implants remains
      a controversial issue. The Dark Agouti (DA) rat has been shown recently to have a
      high susceptibility for developing arthritis. This study determined the
      arthritogenic potential of silicone gel, silicone oil, and the low molecular
      weight octamethylcyclotetrasiloxane (D4), by either mixing it with bovine
      collagen II (BII) or by injecting silicone gel alone in DA rats. Three separate
      experiments were performed using 110 female DA rats with 10 rats per treatment
      group. The incidence of collagen induced arthritis was as follows: Experiment I
      (6 micrograms BII)- PBS = 0/10, silicone gel = 4/10, and IFA = 8/9; Experiment II
      (125 micrograms BII)- PBS = 0/10, silicone gel = 7/10, IFA = 10/10, 1,000 cs
      silicone oil = 3/10, D4 = 0/10, and 1% D4 in 1,000 cs silicone oil = 1/10;
      Experiment III (adjuvant alone)-IFA = 8/10, silicone gel = 0/10. Anti-BII
      antibodies were formed in most of the rats treated with either silicone gel or
      IFA mixed with BII and these groups of rats showed a positive DTH reaction. The
      PBS treated rats were negative for both anti-BII antibodies and DTH reaction.
      Silicone gel taken from a commercial breast implant thus is capable of mediating
      collagen induced arthritis in the DA rat. However, silicone gel alone does not
      appear to be arthritogenic.

PMID- 8579730
TI  - Genomic analysis of collagen and endogenous virus loci in the UCD-200 and 206
      lines of chickens, animal models for scleroderma.
AB  - University of California at Davis (UCD) lines 200 and 206 chickens develop a
      hereditary systemic scleroderma-like connective tissue disease characterized by
      severe lymphocytic infiltration and excessive accumulation of collagen in skin
      and internal organs. The immune system seems to play an important role in the
      development and/or perpetuation of this condition. The main goal of our work with
      this strain is the investigation of interactions between endothelial cells,
      lymphocytes, macrophages and fibroblasts leading to the proliferation of the
      latter and to excessive collagen synthesis and/or deposition. One aim of the
      present study was to clarify whether UCD-200 and 206 chickens have a defect of
      collagen genes at the genomic level by means of restriction fragment length
      polymorphism (RFLP) analysis using non-radioactively labelled cDNA probes
      specific for chicken alpha 1(I), alpha 2(I), alpha 1(II), alpha 1(III), alpha
      1(VI), alpha 2(VI), and alpha 3(VI) (pro) collagens. As in the human disease, no
      gross alteration at the genomic level of collagen genes has been found, thus
      providing the UCD-200/206 model to be appropriate for studying the altered
      collagen metabolism in systemic sclerosis (SSc). In addition to the RFLP analysis
      of procollagen genes, we investigated the endogenous avian leukosis virus loci
      (ev) of UCD-200 and 206 chickens by means of Southern blot analysis of Sac I and
      BamH I digested DNA samples using pRAV-2, a Rous sarcoma virus specific probe,
      for hybridization. Most UCD-200 and 206 chickens harbour evs 1, 3 and 10 similar
      to the healthy control UCD-058, but they also contain a novel ev characterized by
      a 4.2 kb Sac I fragment and a 6.1 kb BamH I fragment, which we would like to
      designate ev 23. So far, the role of ev 23 in the development of avian
      scleroderma is unclear; for further analysis classical crossbreeding experiments
      are necessary and are underway.

PMID- 8579731
TI  - Delayed graft function does not influence long-term outcome in cadaver kidney
      transplants without mismatch for HLA-DRB1.
AB  - The currently study focused on the influence of delayed graft function on the
      long-term graft success rate in cadaver kidneys without any mismatches for HLA
      DRB1. Donor-recipient HLA-DRB1 was determined by the significant two-locus
      linkages of HLA-B and -DRB1. The overall 5-year graft success rate was 88% in an
      HLA-DRB1-compatible group, significantly higher than the 69% in an HLA-DRB1
      mismatch group (P < 0.05) and the 66% in an HLA-DR mismatch (P < 0.01). Delayed
      graft function was observed in 182 of 223 transplants. This high incidence of 82%
      is due to the fact that, in Japan, kidney procurement may only occur after
      cardiac arrest. The incidence did not differ in each group. The 5-year success
      rate for grafts with delayed function was 87% in the HLA-DRB1-compatible group,
      again significantly superior to the 68% in the HLA-DRB1 mismatch group and the
      63% in the HLA-DR mismatch cases (P < 0.05). There was, thus, no difference in
      graft success rate for each group, with or without delayed graft function.
      Consequently, we feel that delayed graft function has no impact on the long-term
      outcome in transplants without mismatches for HLA-DRB1.

PMID- 8579733
TI  - Assessment of hepatic viability during cold ischemic preservation.
AB  - A reliable and easy method for assessing the viability of a cold ischemia
      preserved donor liver prior to transplantation into the recepient is needed.
      Based on an earlier study, we hypothesized that liver free fatty acid (FFA)
      leakage into the preservation fluid may be a useful, atraumatic indicator of
      irreversible ischemic injury. The aim of the present study was to determine the
      time course and magnitude of liver FFA release into the preservation solution and
      its correlation with the duration of cold ischemic preservation compatible with
      survival after transplantation. Rat livers (n = 48) were flushed and preserved
      with University of Wisconsin (UW) solution at 4 degrees C for 0, 12, 24, and 48
      h. Thereafter, half of the livers were analyzed for preservation fluid FFA (gas
      liquid chromatography) and protein. The other half were perfused with Krebs
      Henseleit (KH) solution at 37 degrees C for 1 h. Bile secretion and liver enzyme
      release (SGOT, SGPT, and LDH) were measured in addition to perfusate FFA and
      protein. Total FFA in the preservation fluid was 24 micrograms/g wet tissue after
      12 h; it increased sharply 2.6-fold after 24 h and 3.7-fold after 48 h of
      preservation. Bile production was normal after 12 h of preservation but fell by
      20% and 54% after 24 h and 48 h, respectively. LDH release rose from a value of
      20 U/l at 0 time to 120 U/l and 260 U/l after 24 h and 48 h of preservation.
      These results suggest that liver viability declines sharply between 12 and 24 h
      of cold ischemic preservation, which corresponds with a sharp decrease in the 1
      week survival from 100% to 33% after 12 h and 24 h, respectively, of cold
      ischemic preservation. We conclude that measuring FFA and LDH in the preservation
      solution of donor livers may be a useful means of assessing the quality of the
      cold-preserved liver before insertion into the recipient. We also speculate that
      a "threshold" FFA level in the UW preservation fluid indicating irreversible
      damage may be in the order of 35 micrograms total FFA/g liver. Studies on the
      clinical applicability of our findings are currently under way.

PMID- 8579732
TI  - In vitro evaluation of donor liver preservation fluids on human hepatocyte
      function.
AB  - Successful liver transplantation depends on adequate preservation of cellular
      function. We therefore tested the effects of two currently used liver
      preservation fluids, Euro-Collins (EC) solution and University of Wisconsin (UW)
      solution, on the viability and some functional activities of hepatocytes isolated
      from human livers. Cells in primary culture were maintained under hypoxic (95%
      N2/5% CO2) and hypothermic (4 degrees C) conditions for 24 h, either in EC or UW
      solution. This treatment did not result in significant hepatocyte damage, as
      judged by phase contrast microscopy, intracellular LDH release, and the MTT
      mitochondrial test. However, neutral red uptake indicated that lysosomal
      functions were slightly affected (35% decrease) when compared to control
      conditions. At the end of the hypoxia/hypothermia period, hepatocyte monolayers
      were incubated at 37 degrees C under normoxic conditions for 24 h, in order to
      simulate the reperfusion of a transplanted liver. Three drugs--midazolam,
      diazepam, zidovudine--were used as diagnostic substrates to check the metabolic
      abilities of human hepatocytes replaced in normal conditions. Both phase I
      (hydroxylation, demethylation) and phase II (glucuronidation) metabolic reactions
      were affected by the hypoxia/hypothermia shock. Indeed, a 30%-50% decrease in
      these activities was observed as compared to values obtained in control
      hepatocytes. No difference could, however, be found at the cellular level
      regarding the solution used for cold storage. These results suggest that the
      superiority of UW over EC solution, already reported in clinical practice after
      transplantation of preserved human livers, was not due to a better preservation
      of the hepatocytes.

PMID- 8579734
TI  - Hypothermic perfusion preservation of liver: the role of phosphate in stimulating
      ATP synthesis studied by 31P NMR.
AB  - Hypothermic perfusion of rat livers was investigated by 31phosphorus nuclear
      magnetic resonance (31P NMR) spectroscopy using a temperature-controlled module
      that allowed data acquisition at various time points during a 48-h period. The
      livers were perfused with an oxygenated lactobionate/raffinose-based solution
      containing adenosine and inorganic phosphate, and changes in tissue oedema were
      monitored by direct on-line measurements of liver weight changes. Liver tissue
      ATP concentrations, determined by fluorimetric assay, were low immediately after
      organ removal, probably reflecting metabolic stress during the removal period,
      and these increased slightly during the next 3 h. This was reflected by changes
      in the 31P NMR spectra. However, by 24 h ATP levels had increased significantly,
      and these were maintained for up to 48 h, suggesting a shift in the balance
      between energy production and consumption. When inorganic phosphate was replaced
      by another anion (citrate), ATP was maintained at a constant lower level during
      perfusion for 48 h. Tissue weight changes were similar in both groups, suggesting
      that volume control was not affected by the different ATP contents of the livers.
      By combining the temperature-controlled module with a separate perfusion circuit,
      NMR spectroscopy can provide a sensitive method for following energy metabolism
      in the same organ over long periods during hypothermic perfusion.

PMID- 8579735
TI  - Early intragraft inflammatory events of liver allografts leading to chronic
      rejection.
AB  - In this retrospective study, we have investigated the early intragraft
      inflammatory events of 12 liver allografts leading to chronic rejection. The
      cytological findings and clinical follow-up were analyzed in detail. Nine
      patients underwent at least one typical lymphoid activation of acute rejection,
      and three of them were treated more than once. Diagnosis of rejection was based
      on biopsy histology, cytology and liver dysfunction. In addition to the acute
      rejections, cytological analysis demonstrated in 11 of 12 grafts an unidentified
      lymphoid episode that differed from that of rejection. These lymphoid responses
      were associated with viral infections; cytomegalovirus (CMV) infection in 10 of
      12 patients, hepatitis C virus (HCV) infection in 2 of 12 patients, 1 combined
      with CMV, and hepatitis B virus (HBV) infection in 1 patient. Graft dysfunction
      was still seen at the end of the follow-up. Thus, intragraft inflammation caused
      either by acute rejection or by viral infections may be involved in the induction
      of chronic rejection.

PMID- 8579736
TI  - Leukocyte CD18 receptors may be a better target than ICAM-1 ligands for reducing
      histologic evidence of cellular and vascular rejection in the rabbit.
AB  - Building evidence suggests that blocking the ICAM-1/CD18 interaction may affect
      the course of graft rejection. Treatment with monoclonal antibody (mAb) to CD18
      was compared to antibody to ICAM-1 in a rabbit heterotopic heart transplant model
      to determine whether blocking the leukocyte receptor for ICAM-1, CD18, was more
      effective than antibody targeting of the ligand for ICAM-1. Following
      transplantation, 28 recipient rabbits were randomized to receive either placebo,
      mAb to CD18, or mAb to ICAM-1 for 7 days until sacrifice. The cellular rejection
      grade and percentage of arteries with vascular rejection were significantly lower
      in animals treated with anti-CD18 than with anti-ICAM-1. As assessed by
      histology, antibody treatment was more effective in reducing both cellular and
      vascular rejection when directed at the leukocyte receptor CD18 than the ICAM-1
      ligand. These findings suggest that other ICAM ligands may play an active role in
      the immune response and that CD18 may be important for migration of lymphocytes
      through myocardium.

PMID- 8579737
TI  - Soluble tumor necrosis factor-receptors are not a useful marker of acute
      allograft rejection: a study in patients with renal or cardiac allografts.
AB  - In this study, we investigated soluble tumor necrosis factor receptor (sTNF-R)
      levels in plasma of patients with either a kidney or cardiac allograft when
      clinical suspicion of acute rejection was raised. In plasma of patients with
      acute renal graft rejection, the sTNF-R levels were strongly enhanced (20-150
      ng/ml) as compared to plasma of patients with stable renal function. Following
      successful treatment of the rejection, a gradual decline in sTNF-R levels
      occurred with improving renal function, and an inverse correlation between
      creatinine clearance and sTNF-R was found. To determine whether the increase was
      caused by an accumulation of constitutively released sTNF-R and lack of clearance
      by the kidney, or whether the immunological process of the rejection caused the
      enhancement, we measured sTNF-R in patients suffering from acute cardiac graft
      rejection but with predominantly stable kidney function. Rejection of a cardiac
      graft did not lead to a significant enhancement of sTNF-R levels. However,
      treatment with ATG or OKT3 did cause enhanced sTNF-R levels, followed by a
      decline that reached starting values after 7 days. These results provide evidence
      that the immune reaction that occurs during rejection of a graft does not per se
      induce discernible changes in sTNF-R levels, whereas that induced by ATG or OKT3
      does. Thus, sTNF-R levels are not reliable marker in transplant recipient
      monitoring.

PMID- 8579738
TI  - Comparison of solutions for preservation of the rabbit liver as tested by
      isolated perfusion.
AB  - The University of Wisconsin (UW) solution consists of a relatively complex
      mixture of agents. In this study we compared simpler preservation solutions,
      namely, histidine-tryptophan-ketoglutarate (HTK) and phosphate-buffered sucrose
      (PBS) with different compositions of UW solution in the isolated perfused rabbit
      liver model. Livers were stored cold for 24 and 48 h. After 24 h of preservation,
      the amount of bile produced in UW-preserved livers was significantly greater (P <
      0.05) than that in HTK-preserved livers. Also, there was less LDH released into
      the perfusate in UW-preserved livers. There was more edema and lower K
      +/Na+rations in HTK-preserved livers than in UW-preserved livers (all data P <
      0.05). After 48 h of preservation, the differences between livers preserved in UW
      or HTK solution were less noticeable than at 24 h and bile production was
      similar. LDH and AST release were greater in HTK-preserved livers than in UW
      livers, but these differences were not statistically significant. Preservation in
      PBS for 48 h was worse than in either UW or HTK solution. Substitution of
      polyethylene glycol (PEG) for hydroxyethyl starch (HES) in 48-h UW-preserved
      livers was not effective. We conclude that solutions simpler in composition than
      UW solution may be effective in kidney transplantation but do not appear suitable
      for successful liver preservation.

PMID- 8579739
TI  - The use of pronase-digested human leukocytes to improve specificity of the flow
      cytometric crossmatch.
AB  - Two-color fluorescence cytometry (FCXM) has recently been introduced to improve
      the detection of anti-HLA antibodies that react to donor cells, especially in
      recipients receiving kidney allografts. Although this assay system is highly
      sensitive, it lacks specificity. Between 70% and 90% of potential kidney
      recipients with a positive FCXM would have been denied transplant if such an
      assay had been used alone to detect antidonor antibodies. Lack of specificity is
      principally due to normal or irrelevant IgG in aggregates or immune complexes
      binding to Fc gamma R receptors on lymphocytes including B cells and a
      significant subset of T cells. To circumvent this problem, we digested Fc gamma R
      receptors on lymphocytes with pronase. We present data demonstrating that pronase
      digestion of lymphocytes does not alter HLA antigenicity. In addition, pronased
      lymphocytes allow one to use either single- or two-color FCXM. With single-color
      FCXM, one can quantitate antibody reactivity to lymphocytes via a cursor (on the
      fluorescence histogram) that separates lymphocytes that do not bind to
      antibodies. We present data demonstrating that this modification renders FCXM
      highly sensitive and specific. In addition, one can discriminate between IgG and
      IgM antibodies that react to lymphocytes.

PMID- 8579740
TI  - Effect of cyclosporin on lung diffusing capacity in renal transplant patients.
AB  - A prospective lung function study pre- and postrenal transplantation was
      performed on 21 patients in order to evaluate whether cyclosporin decreased the
      lung diffusing capacity due to lung toxicity. Initial inclusion criteria were
      absence of respiratory symptoms and normal findings in both chest X-ray and
      pulmonary function tests. Participants had to be nonsmokers. We determined
      spirometry including lung volumes, arterial blood gases, carbon monoxide
      diffusing capacity by the single breath method (DLCOSB), and rate of CO uptake
      per unit of lung volume (KCO) before and 3, 6, and 12 months after
      transplantation. Immunosuppression consisted of prednisone and cyclosporin,
      maintaining total blood levels between 100 and 250 ng/ml. Spirometric and blood
      gases data remained within reference levels during the follow-up. Hemoglobin (Hb)
      pretransplant concentrations remained low, returning to their normal levels post
      transplantation. Pretransplant DLCOSB levels were slightly decreased but fell
      within the therapeutic range after correction for Hb concentration, unlike the
      mean KCO levels which remained slightly diminished despite their correction. In
      post-transplant controls, the values obtained for both DLCOSB and KCO were
      significantly higher at the different post-transplant intervals (P < 0.005) than
      pretransplantation but only when compared without Hb correction. No significant
      differences for DLCOSB were found when corrected values were compared, and an
      improvement in the KCO appeared to be significant at 12 months
      posttransplantation. Based on these findings, we feel that when serum levels are
      within the therapeutic range, cyclosporin fails to alter the respiratory function
      or the pulmonary diffusing capacity of the lung.

PMID- 8579741
TI  - Orthotopic liver transplantation in hemophilia B: a case report.
AB  - Liver transplantation is a treatment modality that is being used with increasing
      frequency in cases of liver-based metabolic defects. This is a case report of a
      patient with hemophilia B who was treated since childhood with factor IX
      replacement for recurrent hemarthroses. Subsequent hepatitis B (HBV) and C (HCV)
      infection had resulted in the development of chronic active hepatitis, ultimately
      leading to cirrhosis. Orthotopic liver transplantation performed for endstage
      liver disease resulted in a rise in factor IX levels from 2% to 83% of normal
      values within 24 h postoperatively, and levels remained above 90% of normal
      values after postoperative day 3 without factor IX replacement. To our knowledge,
      only two cases of hemophilia B treated by orthotopic liver transplantation have
      been reported. This procedure has, however, only been implemented in cases of
      terminal liver insufficiency in hemophiliacs.

PMID- 8579742
TI  - Post-transplant lymphoma in a liver allograft.
AB  - We describe the development of a lymphoma in a liver allograft shortly after
      orthotopic liver transplantation. Aspiration and core biopsies of the nodule were
      persistently negative so that a diagnosis could not be made until the patient
      underwent retransplantation, when examination of the liver resection specimen
      revealed a B-cell lymphoma. Using a rapid technique based on the polymerase chain
      reaction, we were able to demonstrate that the tumor was of donor origin.

PMID- 8579743
TI  - Life-threatening gastrointestinal bleeding after liver transplantation due to
      hepatic artery pseudoaneurysm perforating into the common bile duct. A case
      report.
AB  - A 54-year-old male presented with acute rejection and life-threatening
      gastrointestinal bleeding 2 months following orthotopic liver transplantation.
      Since no bleeding was identified in the entire gastrointestinal (GI) tract,
      hematobilia was first suspected and an arteriocholedochal fistula
      angiographically confirmed. Two days after resection of a pseudoaneurysm of the
      hepatic artery (HA) with primary repair and closure of the bile duct fistula,
      hepatic artery thrombosis (HAT) occurred. Various attempts to revascularize the
      HA eventually failed. Two weeks later, a CT scan showed necrotic areas within the
      two left lateral segments. At relaparotomy, major parts of the bile duct were
      found to be necrotic, and the biliary anastomosis was therefore abandoned and
      necrotic tissue removed. HAT was otherwise well tolerated by the graft and, at a
      further relaparotomy some weeks later, a hepaticojejunostomy was performed. Two
      years after transplantation the patient is well with a normally functioning
      graft.

PMID- 8579745
TI  - Diagnostic criteria and immunopathogenesis of Sjogren's syndrome: implications
      for therapy.

PMID- 8579744
TI  - Transcription factors that control development of the thymic microenvironment.

PMID- 8579746
TI  - Chemokines: new ligands, receptors and activities.

PMID- 8579747
TI  - The credentials of a T-cell epitope.

PMID- 8579748
TI  - BSAP: a key regulator of B-cell development and differentiation.
AB  - B-cell-specific activator protein (BSAP) is a recently identified member of the
      Pax-gene family of transcription factors; in the lymphoid system, BSAP is
      produced only in B cells. Here, Markus Neurath, Eckhard Stuber and Warren Strober
      describe the molecular structure of BSAP and focus on the ability of this protein
      to regulate the expression of B-cell-specific genes. They propose that BSAP is a
      key protein of B cells and that it not only influence B-cell development but also
      influences the balance between B-cell proliferation and immunoglobulin secretion
      at later stages of B-cell differentiation.

PMID- 8579749
TI  - Fas and FasL in the homeostatic regulation of immune responses.
AB  - Studies of the biological effects of Fas signaling, using transformed cell lines
      as targets, indicate that ligation of the Fas receptor induces an apoptotic death
      signal. Chronically activated normal human T cells are also susceptible to Fas
      mediated apoptosis. However, interactions between Fas and Fas ligand can also
      yield a costimulatory signal. Here, David Lynch, Fred Ramsdell and Mark Alderson
      present a model for the role of As and FasL in the homeostatic regulation of
      normal immune responses. They discuss how dysregulation of the Fas apoptotic
      pathway may contribute to certain disease states, including autoimmune disease
      and human immunodeficiency virus (HIV)-induced depletion of CD4+ T cells.

PMID- 8579750
TI  - Nitric oxide production by human monocytes: evidence for a role of CD23.
AB  - Nitric oxide (NO) appears to be an important and pleiotropic bioregulator of
      immune responses. The existence of the NO synthase (NOS) pathway in human
      monocytes/macrophages remains a subject of controversy, despite an increasing
      number of reports suggesting that human monocytes produce NO in vitro in response
      to various stimuli. Here, Bernard Dugas and colleagues consider the arguments
      supporting these conclusions, with particular emphasis on the results obtained by
      ligation of the low-affinity IgE receptor (Fcepsilon RIIb/CD23b).

PMID- 8579751
TI  - Molecular recognition of antigen involves lattice formation between CD4, MHC
      class II and TCR molecules.
AB  - Recent evidence indicates that CD4 stably binds to major histocompatibility
      complex (MHC) class II only after assuming an oligomeric state: the membrane
      distal CD4 D1-D2 module interacts directly with MHC class II, whereas the
      membrane-proximal CD4 D3-D4 module mediates oligomerization. This results in the
      formation of aggregates critical for T-cell activation. The T-cell receptor (TCR)
      regulates specific crosslinking and is itself dependent on lattice formation to
      trigger physiological T-cell responses. Here, Toshiko Sakihama, Alex Smolyar and
      Ellis Reinherz discuss the molecular nature of CD4-MHC class II clustering and
      how, despite each of the component interactions being of low affinity, the
      molecular matrix renders T-cell recognition extremely specific and sensitive.

PMID- 8579752
TI  - Analysis of TCR usage in human tumors: a new tool for assessing tumor-specific
      immune responses.
AB  - Tumor-infiltrating lymphocytes (TILs), through displaying a T-cell receptor (TCR)
      repertoire as heterogeneous as that of normal peripheral blood T cells, show
      overexpression of TCR variable-gene segments that include clonally expanded TCR
      sequences. Here, Marialuisa Sensi and Giorgio Parmiani analyze the available
      information on TCR usage by T cells present in the infiltrate of histologically
      different tumors and suggest that the analysis of TCR sequences represents a
      powerful new tool to assess the in vivo immune response to growing tumors.
      Ultimately, this strategy may lead to the identification and manipulation of T
      cell populations endowed with antitumor reactivity.

PMID- 8579753
TI  - Immunosuppressive retroviral peptides: cAMP and cytokine patterns.
AB  - The mechanism(s) by which retroviral proteins exert immunosuppressive influences
      has remained enigmatic. Here, Soichi Haraguchi, Robert Good and Noorbibi Day
      propose that induction of intracellular cAMP by a synthetic, immunosuppressive,
      retroviral envelope peptide causes a shift in the cytokine balance, leading to
      suppression of cell-mediated immunity by upregulation of interleukin 10 (IL-10)
      and downregulation of IL-2, IL-12 and tumor necrosis factor alpha production.
      This may be a crucial step towards generation of immune dysfunction.

PMID- 8579754
TI  - TCR usage in CTLs recognizing melanoma/melanocyte antigens.

PMID- 8579755
TI  - Th1 and Th2: swinging to a hormonal rhythm.

PMID- 8579756
TI  - Human leukocyte antigen DQ alpha sharing is not increased in couples with
      recurrent miscarriage.
AB  - PROBLEM: The results regarding human leukocyte antigen (HLA) DQ alpha allele
      sharing in recurrent miscarriage couples are conflicting. The purpose of this
      study was to determine the frequency of HLA DQ alpha allele sharing in our
      unexplained recurrent spontaneous abortion (RSA) patients using modern DNA
      analytical techniques. METHODS: DNA was extracted from whole blood samples of 1)
      51 couples with at least three miscarriages, and 2) 43 fertile couples (with at
      least seven children and no known history of recurrent miscarriage). The
      polymerase chain reaction (PCR) was used to amplify the second exon of the HLA DQ
      alpha locus on chromosome 6. Genotypes were identified by allele specific
      hybridization with 12 sequence-specific oligonucleotide probes. RESULTS: 47% of
      recurrent miscarriage couples and 35% of fertile couples shared no alleles. 47%
      of recurrent miscarriage couples compared to 58% of fertile couples shared one
      allele, and 6% of recurrent miscarriage couples and 7% of fertile couples shared
      two alleles. CONCLUSIONS: Reproductive partners with unexplained recurrent
      pregnancy loss have no increased frequency of HLA DQ alpha allele sharing. It is
      unlikely that HLA DQ alpha genotyping will be helpful in the management of
      patients with RSA.

PMID- 8579757
TI  - Immunohistochemical localization of endothelin-1 in placenta and fetal membranes
      in term and preterm human pregnancy.
AB  - PROBLEM: The aim of the study was to determine the ET-1 localization on human
      placenta and fetal membranes and to compare its distribution between term and
      preterm pregnancies in laboring and non-laboring tissues. METHODS: Tissues
      obtained from nine term elective cesarean section, eight spontaneous vaginal term
      delivery, and 13 preterm delivery from both cesarean section (N = 6) and vaginal
      delivery (N = 7) were studied by immunohistochemistry. RESULTS: Immunoreactive ET
      1 (IR-ET-1) was detected in villous and nonvillous trophoblast in all groups,
      although laboring tissues showed strong staining in the syncytiotrophoblast of
      the villi. ET-1 immunostaining of endothelial cells was observed in all placental
      villous vessels with a considerable variability within groups. In the fetal
      membranes, intensive immunopositive staining was observed in the chorionic
      trophoblast following vaginal deliveries in term and preterm tissues.
      CONCLUSIONS: This is the first study to report the localization of IR-ET-1 in
      human fetal membranes and placenta, and suggests that amnion and trophoblast
      represents a source of ET-1 production or, alternatively, a site for ET-1
      binding.

PMID- 8579758
TI  - Reciprocal alteration in circulating TJ6+ CD19+ and TJ6+ CD56+ leukocytes in
      early pregnancy predicts success or miscarriage.
AB  - PROBLEM: TJ6 is a cytokine whose membrane form is regularly expressed on the B
      lymphocytes of women during pregnancy. In a previous study we have shown that
      pregnancies that end in a spontaneous abortion are characterized by an increase
      in natural killer (NK) cells and that NK cells in these pregnancies also
      expressed TJ6, whereas NK cells from pregnancies that terminate normally neither
      increase in number nor do they express significant amounts of the cytokine.
      METHODS: To evaluate the ability of TJ6 to predict pregnancy outcome, 61 blood
      samples from pregnant women were studied. Blood samples were drawn between 5 and
      12 weeks of gestation and analyzed for lymphocyte expression of TJ6 using Cytoron
      Absolute flow cytometry and two-color fluorescence. The percentage of CD19+ (B)
      cells and CD56+ (NK) cells that expressed TJ6 was calculated, and this percentage
      was correlated with subsequent pregnancy outcome classified as successful (viable
      birth) or unsuccessful (abortion, stillbirth). TJ6 CD19 and TJ6 CD56 was
      determined in 32 blood samples from women with successful pregnancy outcomes and
      29 samples from women with unsuccessful pregnancy outcome. RESULTS: The mean TJ6
      CD19 expression for successful pregnancies was 10.6% and for unsuccessful
      pregnancies was 5.1% (P < 0.03). The mean TJ6 CD56+ percentage of circulating
      cells that express TJ6 expression for successful pregnancies was 3.3% and for
      unsuccessful pregnancies was 10.4% (P = 0.02). All unsuccessful pregnancies had
      less than 90% of circulating CD19 cells express TJ6 and/or greater than 50% of
      circulating CD56 cells express TJ6. Use of the expression of TJ6 on CD19 and CD56
      cells during the first trimester predicts viable pregnancy with a sensitivity of
      100%, specificity of 100%, positive predictive value of 100%, and negative
      predictive value of 100%. CONCLUSIONS: The work now being reported validates the
      hypothesis that expression of TJ6 on NK cells obtained from pregnant women
      predicts the outcome of pregnancy. In addition we show that this prognosticator
      can be reliably demonstrated early in the first trimester.

PMID- 8579759
TI  - Effect of leukemia inhibitory factor on human cytotrophoblast differentiation
      along the invasive pathway.
AB  - PROBLEM: Leukemia inhibitory factor (LIF) is a pleiotropic secreted cytokine that
      was shown to be essential for blastocyst implantation in mice. Since it is well
      documented that LIF is produced by the human endometrium, we wondered if this
      cytokine was capable of modulating the invasive behaviour of human
      cytotrophoblastic cells (CTB). METHODS: CTB were isolated and purified from first
      trimester abortions, separated or not into cells bearing a laminin or a
      fibronectin receptor (alpha 6 beta 4 or alpha 5 beta 1 respectively) using
      specific monoclonal antibodies and magnetic particles. RESULTS: We observed that
      rhLIF inhibited the secretion of gelatinases and of hCG by CTB but remained
      without effects on the secretion of fetal fibronectin (fFN). These effects were
      exerted on different CTB subsets: although rhLIF inhibited the secretion of
      gelatinases by alpha 6 positive cells, it stimulated the fFN secretion by alpha 5
      positive cells. The inhibitory effect of rhLIF on the secretion of hCG was mainly
      due to its effect on the hCG secretion of alpha 5 positive CTB. CONCLUSIONS:
      Taken together these results suggest that in vitro LIF inhibits the
      differentiation of CTB towards an invasive phenotype by inhibiting the secretion
      of metalloproteinases, by increasing the deposition of fFN into the extracellular
      matrix and by inhibiting the differentiation of CTB into syncytium.

PMID- 8579760
TI  - Regulation of human decidual cell macrophage inflammatory protein-1 alpha (MIP-1
      alpha) production by inflammatory cytokines.
AB  - PROBLEM: Inflammation of human gestational tissues is a key pathophysiologic
      event in the genesis of infection-associated preterm labor. Human gestational
      tissues produce several inflammatory cytokines after stimulation with bacterial
      products. These include interleukin-1 beta (IL-1 beta), tumor necrosis factor
      alpha (TNF alpha), and IL-6. Another class of cytokines includes chemokines of
      the "C-C" subclassification such as macrophage inflammatory protein-1 alpha (MIP
      1 alpha). The purpose of this study was to determine whether cultured human
      decidual cells produce MIP-1 alpha in response to other inflammatory cytokines.
      METHODS: Various concentrations of IL-1 beta, TNF alpha, IL-6, and IL-4 were
      incubated with confluent monolayer cultures of decidual cells isolated from
      normal term placentae for 16 h at 37 degrees C, and MIP-1 alpha concentrations in
      culture supernatants were measured by ELISA. RESULTS: We found that incubation of
      decidual cells with IL-1 beta, TNF alpha, and IL-4 resulted in significant
      concentration-dependent increases in MIP-1 alpha production. IL-6 had no effect
      on MIP-1 alpha production. CONCLUSIONS: Our data are the first to show that human
      decidual cells in culture produce MIP-1 alpha in response to other inflammatory
      cytokines. We suggest that decidual cell production of MIP-1 alpha is an
      important early event in the pathophysiology of infection-associated preterm
      labor.

PMID- 8579761
TI  - Decreased expression of endometrial decay accelerating factor (DAF), a complement
      regulatory protein, in patients with luteal phase defect.
AB  - PROBLEM: We investigated the level of decay accelerating factor (DAF) in the
      endometrium of luteal phase defect (LPD) patients, before and after treatment
      with progesterone. METHODS: Endometrial samples from fourteen normal-cycling
      controls and six samples from infertility patients with LPD before and four
      samples after progesterone treatment were stained by anti-DAF IgG using
      immunohistochemistry. RESULTS: Mean DAF OD in LPD patients was 15% compared to
      60% in the control group. The mean DAF OD was 88% after treatment with
      progesterone. CONCLUSION: Results support interpretation that progesterone
      upregulates DAF while decreased progesterone may be associated with reduced
      expression of the DAF in LPD patients.

PMID- 8579762
TI  - Normal uterine cervix: characterization of isolated lymphocyte phenotypes and
      immunoglobulin secretion.
AB  - PROBLEM: Isolation of viable cervical lymphocyte populations and characterization
      of their function in healthy tissue is necessary to understand immunity in the
      genital tract. METHODS: Normal, cervical tissue was digested using a multi
      enzymatic digestion procedure. Lymphocytes were characterized using FACS analysis
      and ELISPOT analysis for immunoglobulin secreting cells. RESULTS: Following the
      digestion procedure, 0.16 x 10(6) +/- 0.8 cells/g of tissue with a viability of
      90-98% were isolated from normal cervical tissue. FACS analysis determined that B
      lymphocytes were the predominant cell type in normal cervical tissue representing
      a significantly higher percentage than that found in peripheral blood (P =
      0.015). T lymphocytes and NK cells represented a significantly lower percentage
      than that found in peripheral blood (P = 0.0001 and 0.026, respectively). The
      largest percentage of immunoglobulin secreting cells isolated were secreting IgG
      followed by IgA. A limited number of IgM secreting cells were detected. IgA2
      secreting cells represented 34.46 +/- 4.6% of the total number of IgA plasma
      cells. CONCLUSION: These studies represent the first analysis of viable
      mononuclear cells isolated from normal cervical tissue. The results form a
      baseline from which it will now be possible to compare changes that occur at the
      cervical squamocolumnar junction in response to infection or neoplasia.

PMID- 8579763
TI  - Effect of RU-486 and related compounds on the proliferation of cultured
      macrophages.
AB  - PROBLEM: Macrophages are implicated in the pathophysiology of endometriosis and
      are influenced by anti-inflammatory steroids as well as anti-oxidants. METHODS:
      We tested the effect of RU-486, an antiprogesterone, antiglucocorticoid and an
      antioxidant, on the proliferation of RAW macrophages. RESULTS: The incorporation
      of 3H-thymidine was significantly inhibited by both progesterone and RU-486.
      Progesterone and RU-486, in combination, synergistically inhibited macrophage
      growth. In contrast, dexamethasone-stimulated growth was antagonized by RU-486 in
      a dose dependent manner. ZK 112,993 which is structurally related to RU-486 but
      lacks antioxidant properties, also inhibited thymidine incorporation. The
      synergistic effect of RU-486 and ZK 112,993 with progesterone implicate a
      mechanism of action separate from receptor bound antagonists. A cell permeable
      antioxidant, pyrrolidine dithiocarbamate was very effective in inhibiting the
      incorporation of 3H-thymidine into cells. CONCLUSIONS: These results suggest
      novel therapeutic modalities in the management of endometriosis via
      antiglucocorticoid as well as antioxidant mechanisms.

PMID- 8579764
TI  - Hematopoietic stem cell antigen-1 (Sca-1) expression in different lymphoid
      tissues of female mice treated with GnRH agonist.
AB  - PROBLEM: Our earlier studies have demonstrated a general suppression of leukocyte
      maturation upon GnRH agonist treatment in mice and suggested a potential effect
      at an early stem cell stage of leukocyte development. METHOD: Three-week old
      Balb/c and C57BL/6 female mice received 50 micrograms injections of Lupron depot
      or placebo. Sequential changes in Sca-1+ cells in the bone marrow, thymus, blood
      and spleen were studied by flow cytometry. RESULTS: In bone marrow, the absolute
      numbers of Sca-1+ cells were significantly decreased at 2 weeks in C57BL/6 mice
      whereas a decreasing trend was noted in Balb/c mice following agonist
      administration. Concomitantly, thymocytes expressing Sca-1+ cells were
      significantly increased at 2 weeks in C57BL/6 mice, but were significantly
      decreased in Balb/c mice. Significant decreases in Sca-1+ cells were also
      observed in spleen and blood in Balb/c mice whereas no significant differences
      were observed in C57BL/6 mice. CONCLUSIONS: These data suggest GnRH agonists
      affect hematopoietic stem cell development in mice. The effects observed vary
      with different genetic backgrounds. In Balb/c mice these effects are more
      pronounced, and appear to result in the inhibition of stem cell maturation. In
      contrast, GnRH agonist enhances stem cell maturation in C57BL/6 mice.

PMID- 8579765
TI  - Restoration of ACTH/cortisol and LH responses to naloxone by chronic dopaminergic
      treatment in Parkinson's disease.
AB  - Naloxone is unable to stimulate ACTH/cortisol secretion in patients with de novo
      Parkinson's disease, suggesting a reduced endogenous opioid control of the
      hypothalamic-pituitary-adrenal axis in parkinsonian patients. In the present
      study we examined whether Parkinson's disease also impairs the secretion of LH,
      which is under the inhibitory control of different opioid peptides than
      ACTH/cortisol. In addition, we examined whether a chronic dopaminergic therapy
      for at least one year with levodopa (450 mg/day) plus benserazide (112.5 mg/day)
      in 3 divided oral doses/day of Madopar modifies the ACTH/cortisol and/or the LH
      response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 hours). Ten
      parkinsonian patients (aged 52-62 years) and 8 normal controls (50-60 years) were
      tested with naloxone and in a different occasion with normal saline. The
      parkinsonian patients were tested both before and after dopaminergic treatment.
      Tests started at 09.00 h and lasted 2.5 hours. Basal ACTH/cortisol and LH levels
      were similar in all groups. During saline tests, ACTH/cortisol levels showed a
      slight physiological decline in all groups, whereas LH levels remained constant.
      Naloxone administration significantly increased the plasma levels of
      ACTH/cortisol and LH in the normal controls, but not in the parkinsonian patients
      before the dopaminergic treatment. In contrast, dopaminergic therapy restored
      significant ACTH/cortisol and LH responses to naloxone in parkinsonian patients.
      In fact, after levodopa plus benserazide, naloxone-induced ACTH, cortisol and LH
      increments in parkinsonian patients were significantly higher than before therapy
      and were indistinguishable from those observed in the normal controls. These data
      suggest that in men Parkinson's-related dopaminergic alterations may underlie the
      defective endogenous opioid control of ACTH/cortisol and LH secretion.

PMID- 8579766
TI  - L-Dopa improves colour vision in Parkinson's disease.
AB  - In recent studies disorders of colour vision in Parkinsonian patients have been
      demonstrated. Up to now, the influence of dopaminergic treatment on those
      phenomena remains unclear. We therefore performed a colour vision test
      (Farnsworth-Munsell 100 Hue Test) in 19 patients with Parkinson's disease before
      and after the oral application of the morning dose of L-Dopa. The colour
      discrimination was significantly improved after the ingestion of L-Dopa. There
      was no different effect of L-Dopa on the blue-yellow or red-green axis of colour
      vision. The morphological structures responsible for these colour vision
      disturbances are unknown, but it can be concluded that the dopamine deficiency in
      Parkinson's disease is not restricted to the basal ganglia but may involve the
      visual system as well.

PMID- 8579767
TI  - A new metabolic pathway of L-threo-3,4-dihydroxyphenylserine, a precursor amino
      acid of norepinephrine, in the brain. Studies by in vivo microdialysis.
AB  - The metabolism and the effects of L-threo-3,4-dihydroxyphenylserine (L-threo
      DOPS) were studied in the rat brain striatum by in vivo microdialysis. In the
      brain L-threo-DOPS was metabolized by 3 different enzymes; aromatic L-amino acid
      decarboxylase, catechol-O-methyltransferase, and DOPS-aldolase. DOPS-aldolase was
      the main enzyme which metabolizes L-threo-DOPS. The amounts of the metabolites by
      L-amino acid decarboxylase (norepinephrine and its metabolites) were 0.4% of the
      total amounts of metabolites detected in the dialysate, while those by catechol-O
      methyltransferase, 2.1%, and by DOPS-aldolase, 97.5%, after 100 min perfusion of
      L-threo-DOPS. L-threo-DOPS was found to increase extracellular levels of dopamine
      and serotonin, and to inhibit monoamine catabolism in the brain. Inhibition of
      DOPS-aldolase should improve its effectiveness as the supplement therapy of
      norepinephrine.

PMID- 8579768
TI  - Effects of trihexyphenidyl and L-dopa on brain muscarinic cholinergic receptor
      binding measured by positron emission tomography.
AB  - The effects of pharmacological intervention on brain muscarinic cholinergic
      receptor (mAChR) binding were assessed in seven patients with Parkinson's disease
      by positron emission tomography and carbon-11 labelled N-methyl-4-piperidyl
      benzilate ([11C]NMPB). [11C]NMPB was injected twice, approximately 2 hours apart,
      in each patient, to assess the effect of single doses of 4 mg of trihexyphenidyl
      (n = 5) or 400 mg of L-dopa with 57 mg of benserazide (n = 2) on the binding
      parameter of mAChRs (K3). There was a mean 28% inhibition of K3 values in the
      brain in the presence of trihexyphenidyl, which was assumed to reflect mAChR
      occupancy. No significant change in K3 was observed in the presence of L-dopa.
      This study demonstrates the feasibility of measuring mAChR occupancy by an
      anticholinergic medication with PET.

PMID- 8579769
TI  - Reference memory is affected by transient bilateral clamping of the carotid
      arteries in rats (BCCA).
AB  - Rats were subjected to 60 min of bilateral clamping of the carotid arteries
      (BCCA) in pentobarbital anaesthesia and tested in a hole board with 8 of the 25
      holes baited with food pellets hidden in a serial order. All rats learned to
      recognize the pattern as a reference during an acquisition period at 2-14 days
      post surgery, i.e. reference memory. During the recall tests 29-37, 165-175 and
      240-250 days later BCCA animals showed a decrease in memory revealing a
      significant increase in reference memory errors. The number of working memory
      errors, i.e. reexamination of inspected previously baited holes, did not differ
      from those of sham operated controls. The number of pellets eaten in serial order
      from hole 1 to hole 8 was significantly decreased in BCCA animals compared with
      controls, while the number of holes inspected by the animals in the two groups
      were the same. Thus the observed behaviour changes appear not to be caused by
      motor or motivation deficiencies.

PMID- 8579770
TI  - A comparison of multiplex and simplex families with Alzheimer's disease/senile
      dementia of Alzheimer type within a well defined population.
AB  - A study was made on 150 clinically demented patients presenting at autopsy at
      Umea University Hospital in Sweden. In 90 of the cases dementia was considered to
      be primary in nature and of these forty six per cent (41 cases), fulfilled both
      the clinical and histopathological criteria for the diagnosis of Alzheimer's
      disease/Senile dementia of Alzheimer type (AD/SDAT). The families of these 41
      AD/SDAT cases were then studied, and a family history obtained through interviews
      with multiple family informants and from civil and medical records. Additional
      diseased family members suffering from progressive dementia (multiplex families)
      were observed in 12 probands out of 41 (29%). Multiplex families exhibited
      similar clinical and histopathological characteristics as simplex families
      containing a single affected individual. The secondary cases in the multiplex
      families exhibited similar demographic and clinical characteristics as the
      probands. 39% of the multiplex and 14% of the simplex cases had an early age of
      onset of the disease, that was under 65 years. The overall prevalence of
      progressive dementia disorders in the 41 families was 5.9%. The prevalence of a
      progressive dementia disorder was 11% in the multiplex families (14% for the
      early onset cases) and 3.5% in the simplex families (2% for the early onset
      cases). The prevalence of progressive dementia disorder for family members who
      had passed the mean age of the onset of the disease for their family, was 45% for
      multiplex and 18% for simplex families. Furthermore the incidence rate for
      dementia was significantly higher (p < 0.005) in multiplex families (5.5 per
      1,000 person years) when compared to simplex families (2.5 per 1,000 person
      years). No differences could be seen in parental age at birth of the diseased
      when comparing the two sets of families. However in multiplex families the
      duration of the disease was significantly (p < 0.025) shorter, in subjects with
      parental age at birth over 35 years compared to those with a parental age under
      35 years. The multiplex families contained significantly (p < 0.025) larger
      sibships; and showed a significantly lower age of onset for the disease (p <
      0.001), and a significantly longer duration of disease (p < 0.05) compared to the
      simplex families. A significant intra familial correlation of age at disease
      onset was observed in both sets of the families.

PMID- 8579771
TI  - kappa-1 Opioid receptors of the temporal cortex are preserved in Alzheimer's
      disease.
AB  - The binding of [3H]-U-69593 and [3H]-CI-977 to kappa-1 opioid receptors has been
      examined in the temporal cortex of postmortem brains from patients with
      Alzheimer's disease and age-matched controls using quantitative autoradiography.
      There was no significant difference between Alzheimer and control subjects in the
      level of [3H]-U-69593 and [3H]-CI-977 binding, but ChAT activity was markedly
      reduced (by 73% compared to controls). These results are not consistent with a
      presynaptic localisation of kappa-1 receptors on cholinergic terminals in human
      temporal cortex.

PMID- 8579772
TI  - Fetal mild hydronephrosis and chromosomal defects: relation to maternal age and
      gestation.
AB  - The presence of multiple ultrasonographic abnormalities is associated with a
      significantly increased risk of chromosomal defects, while for isolated
      abnormalities, the association is less clear. In a study of 1,177 fetuses with
      mild hydronephrosis at 16-26 weeks of gestation, the fetal karyotype was abnormal
      in 86 (7.3%) of the cases and the most common chromosomal defects were trisomies
      21, 18 and 13. The frequency of chromosomal defects increased with the number of
      additional abnormalities and for each chromosomal defect there was a
      characteristic pattern of associated abnormalities. However, in the 805 fetuses
      with apparently isolated hydronephrosis there were 5 (0.62%) with trisomy 21. On
      the basis of the maternal age and gestational age distribution of the population
      the expected frequency of trisomy 21 was 0.40%, which was not significantly
      different from the observed (0.62%). To demonstrate that such a difference is
      significant, it would be necessary to investigate at least 1 million pregnancies.
      In the meantime, parents could be counselled that the presence of mild
      hydronephrosis does not increase significantly the risk that the fetus has
      trisomy 21. Alternatively, the risk is 1.6 times higher than the maternal age and
      gestational age-related risk.

PMID- 8579773
TI  - Maternal age and gestational age-specific risk for chromosomal defects.
AB  - This study provides estimates of risks for a wide range of chromosomal defects
      taking into account maternal age as well as the gestation at assessment. The
      estimates make it possible to counsel patients presenting at different stages of
      pregnancy. At the same time, they offer the possibility of evaluating the
      efficacy of biochemical and ultrasonographic markers in identifying fetuses with
      chromosomal defects.

PMID- 8579774
TI  - Maternal age-dependent and sex-related changes of gestational serum alpha
      fetoprotein.
AB  - Maternal serum alpha-fetoprotein (MSAFP) concentration values were measured in
      relation to maternal age and fetal sex in the 16th to 20th gestational weeks in
      samples taken from 9,556 pregnancies with the outcome of live, mature and healthy
      infants. Our results show positive significance between MSAFP concentration and
      maternal age (p < 0.001); we also found significantly higher AFP values in male
      fetuses than in female fetuses (p < 0.001). This specificity is by all
      probability due to the change in the physiologic AFP concentration of the
      pregnant woman. Considering maternal age and the new percentile AFP values, cut
      off concentration values can be corrected, thus the quality of routine AFP
      screening can be improved. At the same time, with the application of the above
      parameters, a more effective selection of pregnancies at high risk for Down
      syndrome can be achieved.

PMID- 8579775
TI  - Management of platelet and RhD maternal immunizations by PCR phenotypings after
      early amniocentesis.
AB  - This study evaluates the possibilities of prenatal diagnosis of maternofetal
      platelet and anti-RhD incompatibilities by using molecular typing on amniocytes.
      Twenty-four amniocenteses were performed between 15 and 35 weeks of gestation
      (WG), 19 times for study of the fetal karyotype and 5 times because of anti-D
      immunization. HPA-1, HPA-3 and HPA-5 platelet phenotypes using PCR-RFLP and RhD
      phenotypes using amplification-refractory mutation system PCR were assessed in
      amniotic fluid and compared with those of fetal (15 times) or newborn (9 times)
      blood and with parental phenotypes (46 blood samples). The four phenotypes were
      always determined in amniocytes, and no discrepancies with fetal blood or
      parental phenotypes were noted. The reliability and low iatrogenicity of this
      method makes it suitable for amniocentesis from 15 WG onward in any woman whose
      spouse is likely to be heterozygous. These allow radical change with a clear
      beneficial effect in obstetrical care of immunized women.

PMID- 8579776
TI  - Cardiac defects in 1st-trimester fetuses with trisomy 18.
AB  - In trisomy 18, echocardiographic studies of affected neonates and pathological
      studies of stillbirths and infants have demonstrated a high incidence of cardiac
      defects. Fetal trisomy 18 can now be detected at 11-14 weeks of gestation,
      providing the opportunity to examine the incidence of cardiac defects at this
      gestational age. In 19 fetuses with trisomy 18 pathological examination of heart
      and great vessels was carried out after termination of pregnancy at 11-14 weeks
      of gestation. The abnormal karyotype was diagnosed by chorion villus sampling in
      pregnancies with increased fetal nuchal translucency thickness. All 19 fetuses
      had cardiac defects, and the commonest were ventricular septal defects in 16
      (84%) and valvular abnormalities in 16 (84%). In 14 of the 16 cases with valvular
      abnormalities more than one valve was affected. The great vessels were available
      for examination in 18 of the 19 cases, and in 10 there was a hypoplastic aortic
      isthmus or pulmonary trunk. In 6 (32%) cases there was persistence of the left
      superior vena cava. In 1st-trimester fetuses with trisomy 18, the frequency of
      perimembranous ventricular septal defects and valvular abnormalities is similar
      to that in affected neonates. Haemodynamic changes due to the valvular
      abnormalities, especially imperforate valves, and hypoplasia of the great vessels
      may be the underlying mechanisms for the increased nuchal translucency of
      trisomic fetuses. Persistence of the left superior vena cava may result from
      venous congestion of head and neck.

PMID- 8579777
TI  - Prenatal diagnosis of a (X;X) translocation by fluorescence in situ hybridization
      and laser scanning image cytometry.
AB  - A de novo structural abnormality of one X chromosome was prenatally detected in a
      female fetus. This chromosomal abnormality has been analyzed by conventional
      cytogenetic methods, fluorescence in situ hybridization, and laser scanning image
      cytometry. The association of these techniques has demonstrated that this anomaly
      corresponds to a (X;X) translocation. Analysis of hybridization signals by laser
      scanning image cytometry allowed to localize that the breakpoints were at the X
      centromeric region and Xp11.3, respectively. These results show the usefulness of
      image analysis and fluorescence in situ hybridization for a rapid
      characterization of de novo structural chromosome anomalies in prenatal
      diagnosis.

PMID- 8579778
TI  - Congenital diaphragmatic hernia: prognosis and prenatal detection.
AB  - Fifty consecutive cases of isolated congenital diaphragmatic hernia were reviewed
      for prenatal ultrasound and neonatal physical findings. These were compared to
      survival and the need for extracorporeal membrane oxygenation (ECMO). No prenatal
      findings predicted survival or the need for ECMO. In left-sided hernias, the
      presence of the liver in the chest predicted (p = 0.02) the requirement for ECMO.
      In a cohort of 13 prenatally diagnosed inborn cases, the ultrasound triad of
      polyhydramnios, mediastinal shift and intrathoracic stomach predicted the
      presence of liver in the chest (p < 0.03).

PMID- 8579779
TI  - Antenatal diagnosis and surgical management of congenital cystic adenomatoid
      malformation of the lung.
AB  - We experienced 12 cases of congenital cystic adenomatoid malformation of the lung
      (CCAM) including 6 cases diagnosed antenatally. They were classified into three
      groups according to the clinical manifestations. Group A was associated with
      hydrops fetalis (n = 3), group B presented with respiratory distress symptoms
      after birth (n = 6), and group C showed no respiratory symptoms (n = 3). All
      cases of group A were lost because of hydrops and respiratory failure due to
      pulmonary hypoplasia. Because a compression of the mass is thought to be a cause
      of hydrops, this group is considered to be a good indication for fetal treatment.
      All cases of group B showed progressive respiratory symptoms a few days after
      birth which were successfully treated surgically. In 2 of 3 cases of group C, the
      lesions decreased in size both antenatally and postnatally. We conclude that
      serial sonographic evaluations for fetal CCAM are important. If the fetus
      develops hydrops, fetal surgery is to be considered. If not, however, fetal
      surgery should not be done, because some lesions can shrink in size, or even
      disappear, while others can be treated successfully after birth by lobectomy or
      even segmentectomy.

PMID- 8579780
TI  - Transabdominal amnioinfusion in preterm pregnancies complicated by fetal growth
      restriction, oligohydramnios and umbilical cord compression.
AB  - Fetal growth restriction with oligohydramnios occurring in the preterm gestation
      is associated with significant fetal morbidity and mortality. We investigated the
      possibility that transabdominal amnioinfusion might relieve acute cord
      compression and allow prolongation of gestation long enough to administer
      corticosteroids. Four patients with fetal growth restriction, oligohydramnios and
      evidence of significant cord compression with otherwise reassuring fetal heart
      rate testing underwent transabdominal amnioinfusion. Pregnancy was prolonged 22,
      38, 10 and 9 days, and cord compression was relieved in all cases. One patient
      showed findings consistent with reversal of chronic hypoxemia with stabilization
      of amniotic fluid index measurements in the normal range and normalization of
      fetal growth. Transabdominal amnioinfusion may be useful as an adjunctive
      technique to prolong pregnancy in preterm gestations with fetal growth
      restriction, oligohydramnios and evidence of umbilical cord compression.

PMID- 8579781
TI  - Conformational preferences of the calliFMRFamides and their free-acid analogues.
AB  - A molecular dynamics study was undertaken to determine the conformational basis
      for the differing activities of the insect neuropeptide hormones calliFMRFamide 3
      (SPSQDFMRF-NH2). calliFMRFamide 5 (APGQDFMRF-NH2) and their corresponding free
      acid analogues (SPSQDFM-RF-OH and APGQDFMRF-OH) in two insect bioassays. A
      simulated annealing protocol was used to determine the range of conformers
      available to the linear peptides. Analysis of the conformers obtained indicated
      that all the peptides exhibited distinct secondary structure preferences. These,
      when correlated with their biological activities, enabled the formulation of
      putative conformation-activity relationships for the peptides.

PMID- 8579782
TI  - Calculations of the phi-psi conformational contour maps for N-acetyl alanine N'
      methyl amide and of the characteristic ratios of poly-L-alanine using various
      molecular mechanics forcefields.
AB  - We generated phi- psi conformational energy contour maps for the N-acetyl alanine
      N'-methyl amide using the molecular mechanics forcefields AMBER, AMBER3, BIO85,
      CFF91, CVFF, MM2, MM3, MM+, AND SYBYL. With MM2, MM3, and MM+ we used a
      dielectric constant of epsilon = 1.5, the default effective value for these
      forcefields. With the other forcefields we used epsilon = 1 and 4, except with
      SYBYL, which, in Spartan 3.1, has no electrostatic term. All forcefields yielded
      the C7eq conformation as a low-energy minimum or the global minimum. Most of the
      forcefields also yielded a minimum-energy conformation in the C5, alpha R, and
      alpha L regions of the phi-psi contour map. Fewer of the forcefields yielded a
      minimum in the C7ax region; however, adiabatic relaxation frequently lowered the
      relative energy of this region. Based on the appearance of the phi-psi maps, the
      following pairs of forcefields were broadly similar (but not identical) to each
      other but dissimilar to the other pairs: AMBER3 and AMBER, BIO85 and CHARMM, MM+
      and MM2, SYBYL and ECEPP, and CFF91 and MM3. We used the data from the phi-psi
      contour maps to compute the characteristic ratio of poly-L-alanine. Most of the
      computed values deviated significantly from the experimental value. Only the
      computed characteristic ratio of CFF91 without adiabatic relaxation at epsilon =
      4 and MM3 without adiabatic relaxation at epsilon = 1.5 agreed with the
      experimental value.

PMID- 8579783
TI  - Selective absorption of radio frequency energy due to collective motion of
      charged domains: case of lysozyme crystal.
AB  - A new aspect of the internal protein motion is pointed-- the electrostatic
      charges of the titratable groups fixed on the protein structure are combined with
      the hinge binding motion of lysozyme domain. Then the lysozyme molecule is
      examined as a system having charges that oscillate with the parameters of the
      mechanical motion. So, from such point of view, the lysozyme molecule becomes
      infrared and radiofrequency active. This model is applied for the case of a
      triclinic lysozyme crystal and the direction of the external electromagnetic flux
      in respect to the main crystal axes is found that corresponds to the best
      conditions for maximal absorption. For the purpose of the experimental
      measurement of the space dependence of the absorption, the direction of the
      incident wave and its polarization are calculated in respect to the main crystal
      planes in case of maximal efficiency of the absorption.

PMID- 8579784
TI  - Conformational analysis of the beta-amyloid peptide fragment, beta(12-28).
AB  - NMR and CD spectroscopy have been used to examine the conformation of the
      peptide, beta(12-28), (VHHQKLVFFAEDVGSNK) in aqueous and 60% TFE / 40% H2O
      solution at pH 2.4. In 60% TFE solution, the peptide is helical as confirmed by
      the CD spectrum and by the pattern of the NOE cross peaks detected in the NOESY
      spectrum of the peptide. In aqueous solution, the peptide adopts a more extended
      and flexible conformation. Broadening of resonances at low temperature,
      temperature-dependent changes in the chemical shifts of several of the CH alpha
      resonances and the observation of a number of NOE contacts between the
      hydrophobic side-chain protons of the peptide are indicative of aggregation in
      aqueous solution. The behavior of beta(12-28) in 60% TFE and in aqueous solution
      are consistent with the overall conformation and aggregation behavior reported
      for the larger peptide fragment, beta(1-28) and the parent beta-amyloid peptide.

PMID- 8579785
TI  - Structure of a tumor associated antigen containing a tandemly repeated
      immunodominant epitope.
AB  - Human mucins are T or S glycosylated tandem repeat proteins. In breast cancer,
      mucins become under or unglycosylated. Two-dimensional nuclear magnetic resonance
      experiments are performed on chemically synthesized mucin tandem repeat
      polypeptides, (PDTRPAPGST-APPAHGVTSA)n the unglycosylated form for n=1,3 where
      (APDTR) constitutes the antigenic sites for the antibodies isolated form the
      tumors in the breast cancer patients. These studies demonstrate how the tandem
      repeats assemble in space giving rise to the overall tertiary structure, and the
      local structure and presentation of the antigenic site(APDTR) at the junction of
      two neighboring repeats. The NMR data reveal repeating knob-like structures
      connected by extended spacers. The knobs protrude away from the long-axis of Muc
      1 and the predominant antigenic site (APDTR) forms the accessible tip of the
      knob. Multiple tandem repeats enhance the rigidity and presentation of the knob
      like structures.

PMID- 8579786
TI  - Imino proton exchange provides an 1H-NMR footprint of protein-DNA interactions:
      general strategy and application to the SRY HMG box.
AB  - A novel 1H nuclear magnetic resonance (NMR) strategy for "footprinting" specific
      protein-DNA target sites is demonstrated. Relative rates of site-specifc imino
      proton exchange in the free and bound DNA duplex are determined by use of laminar
      shifted shaped pulses in NOESY spectra. 2D exchange crosspeaks between imino
      (omega2 dimension) (omega1 dimension) resonances in principle provide site
      specific probes of protein binding. Chemical exchange is distinguished from
      nuclear Overhauser enhancements(NOEs) to bound water by use of ROESY
      spectroscopy. This strategy is illustrated in 1H-NMR studies of the SRY high
      mobility group (HMG) box, the Y-chromosome-encoded "master switch" for testis
      determination in man. In a specific complex between the protein and a 15-basepair
      DNA site, imino-proton exchange was observed to be damped selectively within the
      six basepair subsite 5'-ATTGTT, previously identified by random binding-site
      selection as an optimal SRY target sequence. The extent of damping correlates
      with sites of protein-DNA contacts in the minor groove but not with the magnitude
      of 1H-NMR complexation shifts. SRY binding has recently been shown to introduce
      significant distortions in DNA structure. The DNA is sharply bent and underwound;
      the minor groove is widened and major groove compressed. Our results demonstrate
      that despite such distortions base pairing is stably maintained. Protein binding
      in the DNA minor groove shields DNA imino protons from exchange with solvent.

PMID- 8579787
TI  - High resolution 2D-NMR studies indicating complete assignments and conformational
      characteristics of the NF-kappa B binding enhancer element of HIV-LTR.
AB  - The asymmetrical DNA duplex [5'd(AAGGGACTTTCC)].[5'-d(GGAAAGTCCCTT)] has been
      studied by one- and two-dimensional NMR techniques. The sequence is comprised of
      the actual 10 base-pair long binding site for the transcription factor NF-kappa B
      in the enhancer sequence of the long term repeat (LTR) region of HIV and SIV
      types of retroviruses associated with the AIDS syndrome. Two additional A.T base
      pairs are also included on one end for an added interest in the 12-bp duplex
      sequence with a pseudo dyad-symmetric disposition of the oligopurine and
      oligopyrimidine segments, as it appears in the HIV-1 genome. Phase-sensitive two
      dimensional spectra (NOESY, ROESY, COSY and TOCSY) were obtained at three
      different temperatures (5, 15 and 25 degrees C) for a complete assignment of the
      non-exchangeable protons by tracing through sequence specific intra- and
      internucleotide connectivities. 2D-NOESY spectra were also acquired in aqueous
      (90% H2O-D2O) solutions, with two different methods of water signal suppression,
      to assign the exchangeable protons from specific NOE correlations. Adenine H2
      protons were assigned by the use of NOE correlations and from T1 relaxation time
      measurements. The general spectral features and semi-quantitative interproton
      distance estimates indicate a B-DNA type conformation. However, some distinctly
      unusual features associated with the nucleotides at and immediately adjacent to
      both the 5'-and 3'-ends of AAA/TTT and GGG/CCC segments were noted. The complete
      assignments, and the observed characteristics, will be of significant value in
      studying the complexes of this transcriptionally active DNA domain with the
      protein and other rationally designed DNA binding agents.

PMID- 8579788
TI  - A thermodynamic and mutational analysis of an RNA purine loop as a protein
      binding site.
AB  - The thermal stability and protein binding of a 36 nucleotide RNA hairpin
      containing an internal loop were studied under various solution conditions. Yeast
      ribosomal protein L32 binds to its transcript and small RNAs which reproduce the
      L32 transcript's secondary structure have been examined. Replacement of the
      internal loop with canonical base pairs did not affect the salt dependence of the
      melting temperature suggesting that both molecules adopt a linear shape. Several
      electrostatic contacts are formed on binding to a ribosomal fusion protein, but
      Mg+2 is not required for binding. The RNA protein complex is stable up to 50
      degrees C. Two internal loop deletion mutants have similar thermodynamic
      stabilities and chemical and enzymatic reactivities, but fail to bind the fusion
      protein. However, several of the internal loop bases of the deletion mutants are
      moderately reactive to chemical agents whereas the wild type loop sequence
      displayed a mixed pattern of protection and hyperreactivity.

PMID- 8579789
TI  - What is the basis of sequence-directed curvature in DNAs containing A tracts?
AB  - A variety of solution and gel experiments show that DNAs containing tracts of 4-8
      A's repeated in phase with the helix repeat are curved. Several independent
      analyses of these experiments argue that curvature resides in the A tracts
      themselves. In x-ray crystallographic studies of several DNAs containing A
      tracts, however, the A tracts are uncurved, leading to models in which curvature
      resides in the non-A tracts. This "curved general sequence model" has several
      problems, in our view. We review those, and we describe recent experiments that
      show that the dehydrating agents commonly used in x-ray crystallography markedly
      reduce curvature in gels and in solution, calling into question the ability of
      crystallography to determine the structural basis of DNA curvature. Finally, we
      discuss the critical role of hydration in curved DNAs and suggest new experiments
      that we hope could finally determine exactly which sequences are responsible for
      curvature.

PMID- 8579790
TI  - Trinucleotide models for DNA bending propensity: comparison of models based on
      DNaseI digestion and nucleosome packaging data.
AB  - DNaseI digestion studies (Brukner et al, EMBO J 14, 1812-1818 1995) and
      nucleosomebinding data (Satchwell et al, J. Mol. Biol. 191, 639-659 1986,
      Goodsell and Dickerson, Nucleic trinucleotides. A detailed comparison of the two
      models suggests that while both of them represent improvements with respect to
      dinucleotide based descriptions, the individual trinucleotide parameters are not
      highly correlated (linear correlation coefficient is 0.53), and a number of
      motifs such as TA-elements and CCA/TGG motifs are more realistically described in
      the DNaseI-based model. This may be due to the fact that the DNaseI-based model
      does not rely on a static geometry but rather captures a dynamic ability of ds
      DNA to bend towards the major grove. Future refinement of both models of both
      models on larger experimental data sets is expected to further improve the
      prediction of macroscopic DNA-curvature.

PMID- 8579791
TI  - The effect of monovalent cations on the self-association of cytidylyl-(3-5')
      guanosine and guanylyl-(3'5')-cytidine in aqueous solution.
AB  - The hydrogen-bonding, base stacking, and formation of extended aggregates has
      been investigated for salts of guanylyl-3'-5')-cytidine, GpC, and cytidylyl-(3'
      5')- guanosine, CpG, in which the cation was Na+, K+, or tetramethylammonium
      (TMA+). Variable temperature studies were done at 2-70 degrees C on aqueous
      solutions at pD4 and 8 using 1H NMR and FTIR. At low temperatures it has been
      found that at pD 8 both GpC and CpG form Watson-Crick dimers which stack upon
      each other to form larger species. A slight cation effect is observed below 35
      degrees C which has the order: TMA+ > Na+ > K+. This order suggests that the
      cations are interacting with the phosphate and interactions with the bases are
      unlikely. The 1H NMR spectrum for TMACpG at pD 4 has been assigned and exhibits
      chemical shift differences from those at pD 8 which are consistent with
      protonation of the N3 of the cytidine residue. Based on NMR line broadening, CpG
      at pD 4 has a greater degree of self-association at low temperature than it or
      GpC have at pD 8. A different type of hydrogen bonding and self-association occur
      in CpG at pD 4 compared to pD 8, but the structures are uncertain. Due to hemi
      protonation of the cytidine N3, parallel G-G/C-C+ base paired dimers or G-tetrads
      may be forming.

PMID- 8579792
TI  - Ethidium bromide binding to unstructured and structured 2' GMP.
AB  - For disordered 2' GMP and 5' GMP the ethidium cation (Etd) was found to form 1:1
      and 2:1 Eth:nucleotide complex. For alkali metal solution self-structured 2'GMP
      and 5'GMP Etd was found to form 1:1 and 2:1 Etd: order nucleotide complex. The
      best computer fit was obtained for a structured nucleotide stoichiometry of
      Na4(2'GMP)8. Binding constants for the Etd:disordered 2'GMP complexes were
      determined to be (1.6 +/- 0.1) x 10(4)M(-1) and 6.3 +/- 0.5 M(-1) at O degrees C
      and (1.1 +/- 0.2) x 10(4) M(-1) and 18 +/- 11M(-1) for 5'GMP at 5 degrees C for
      the 1:1 and 1:2 complex, respectively. For the 1:1 and 1:2 2'GMP:Etd species the
      enthalpies were determined to be -19.8 +/- 1.0 kcal/mole and 0.1 +/- 0.3
      kcal/mole, respectively, and the entropies were -53.3 +/- 6.6 eu and 3.9 +/- 1.6
      eu, respectively. Binding constants for the Etd: structured 2'GMP complex,
      assuming a complex with stoichoimetry (Na+)4 (2'GMP)8 for the structured unit,
      were determined to be (1.9 +/- 0.1) x 10(4)M(-1) and 5.8 +/- 0.6) x 10(2)M(-1),
      respectively at 0 degrees C.

PMID- 8579793
TI  - Use of electric linear dichroism and competition experiments with intercalating
      drugs to investigate the mode of binding of Hoechst 33258, berenil and DAPI to GC
      sequences.
AB  - The drugs Hoechst 33258, berenil and DAPI bind preferentially to the minor groove
      of AT sequences in DNA. Despite a strong selectivity for AT sites, they can
      interact with GC sequences by a mechanism which remains so far controversial. The
      2-amino group of guanosine represents a steric hindrance to the entry of the
      drugs in the minor groove of GC sequences. Intercalation and major groove binding
      to GC sites of GC-rich DNA and polynucleotides have been proposed for these
      drugs. To investigate further the mode of binding of Hoechst 33258, berenil and
      DAPI to GC sequences, we studied by electric linear dichroism the mutual
      interference in the DNA binding reaction between these compounds and a classical
      intercalator, proflavine, or a DNA-threading intercalating drug, the amsacrine-4
      carboxamide derivative SN16713. The results of the competition experiments show
      that the two acridine intercalators markedly affect the binding of Hoechst 33258,
      berenil and DAPI to GC polynucleotides but not to DNA containing AT/GC mixed
      sequences such as calf thymus DNA. Proflavine and SN16713 exert dissimilar
      effects on the binding of Hoechst 33258, berenil and DAPI to GC sites. The
      structural changes in DNA induced upon intercalation of the acridine drugs into
      GC sites are not identically perceived by the test compounds. The electric linear
      dichroism data support the hypothesis that Hoechst 33258, berenil and DAPI
      interact with GC sites via a non-classical intercalation process.

PMID- 8579794
TI  - Competition between netropsin and restriction nuclease EcoRI for DNA binding.
AB  - We find that netropsin and netropsin analogue protect DNA from EcorI restriction
      nuclease cleavage by inhibiting the binding of EcoRI to its recognition site. The
      drug -- EcoRI competitive binding constants measured by a electrophoretic gel
      mobility shift assay are in excellent agreement with the nuclease protection
      results for the netropsin analogue and in reasonable agreement for netropsin
      itself. Crystal structures of complexes show that netropsin and EcoRI recognize
      different regions of the DNA helix and would not be expected to compete for
      binding to the restriction nuclease site. The large distortions in DNA structure
      caused by EcoRI binding are most likely responsible for an indirect structural
      competition with netropsin binding. The structural change in the netropsin
      binding region induced by EcoRI binding to its region essentially prevents drug
      association. Given the reciprocal nature of competition, binding of netropsin to
      a minimally perturbed structure then also makes the association of EcoRI
      energetically more costly. Since many sequence specific DNA binding proteins
      significantly bend or distort the DNA helix, drugs that compete indirectly can be
      as effective as drugs that act through a direct steric inhibition.

PMID- 8579795
TI  - DNA-drug interaction. The effects of vitamin C on the solution structure of Calf
      thymus DNA studied by FTIR and laser Raman difference spectroscopy.
AB  - The interaction of calf-thymus DNA with L-ascorbic acid was investigated in
      aqueous solution at pH=7.6 with drug/DNA(P)(P=phosphate) molar ratios (r) of
      1/40, 1/20, 1/10, 1/5, 1/2, 1 and 2. Fourier Transform infrared (FTIR) and laser
      Raman difference spectroscopic techniques were used to establish correlations
      between spectral modifications and drug binding mode, sequence specificity, DNA
      melting and conformational changes, as well as structural variations of drug-DNA
      complexes in aqueous solution. Infrared and Raman spectroscopic results showed
      that at low drug concentration (r = 1/40), a B to A-type conformational
      conversion occurs with minor drug-DNA interaction through A-T bases. At r=1/20,
      drug-PO2 binding was also observed with reduced intensity of DNA inplane
      vibrational frequencies, due to the increased base-stacking interaction and
      duplex stability. At r> 1/20, major perturbations of DNA bases were observed for
      both A-T and G-C base pairs in the major and minor grooves of the duplex.
      Evidence for this comes form the shift of the infrared and Raman vibrations of
      the A-T and G-C bases on drug interaction. At r>1/5, a minor helix
      destabilization occurred with participation of several DNA donor sites in drug
      complexation. The ascorbate anion interaction occurred mainly through H-bonding
      of the acid OH and C-O groups with DNA phosphate, bases and doxyribose donor
      atoms.

PMID- 8579796
TI  - The interaction of copper tetrakis(4-N-methylpyridyl) porphine with
      polynucleotides studied by ultraviolet resonance Raman spectroscopy.
AB  - Resonance Raman spectra are reported for poly[dA.dT]2, poly[dA].poly[dT],
      poly[dG.dC]2, poly[dG].poly[dC], poly[dA.dC].poly[dG.dT] and Calf Thymus DNA in
      interaction with the porphyrin Cu(TMpy-P4). The spectra were obtained under
      conditions of low salinity and a ratio of porphyrin molecules to nucleotide base
      pairs of r = 0.05, with an excitation wavelength of 257 nm. The differences
      between the spectra in interaction with Cu(TMpy-P4) and those of the unmodified
      nucleic acids are interpreted in terms of the structural changes imposed by the
      porphyrin. Two different binding modes have been reported in previous studies, a
      5'CG-3' specific intercalative mode and an A-T specific outside binding mode. Our
      results suggest that this latter mode may show a preference for A-A or T-T sites.
      Furthermore a transition in structure, while remaining within the B-form family
      of structures, is indicated for both poly[dA].poly[dT] and poly[dG.dC]2 upon
      addition of Cu(TMpy-P4).

PMID- 8579797
TI  - The chemical structure of U99194A.

PMID- 8579798
TI  - Detection of psychoactive drugs using 19F MR spectroscopy.
AB  - In vivo 19F resonance spectroscopy measurements of trifluorinated neuroleptics
      (fluphenazine and trifluoperazine) and later trifluorinated antidepressants
      (fluoxetine and fluvoxamine) began with animal experiments in 1983. Using rats
      which have been treated with high oral doses of fluphenazine over a period of
      three weeks in the beginning of these experiments the measurement time was very
      long (up to 10 h). The application of better techniques using surface coils led
      to marked improvement of the signal noise ratio and measurement times in animal
      experiments could be reduced to minutes. These results encouraged us and other
      groups to perform experiments in humans to detect and try to estimate brain
      levels of trifluorinated neuroleptics and antidepressants. The present data of
      several research groups demonstrate that 19F MR spectroscopy has the potential of
      becoming a valuable tool for monitoring drug levels at the site of action. The
      extension of the animal studies to humans might facilitate a better treatment of
      schizophrenic and depressive patients.

PMID- 8579799
TI  - Some considerations on estimating event-related brain signals.
AB  - Understanding the timing of mental acts is one of the prominent questions in
      information processing research. The analysis of event related potentials (ERP)
      with their high temporal resolution might make access to cognition related brain
      activity possible. We consider three major problems which make the application of
      ERPs questionable and then propose some solutions to these problems. The primary
      problem concerns the separation of the ERPs from the background EEG which is not
      related to the stimulus. The most common method used is averaging. We argue that
      this is not the most appropriate method and suggest an alternative for estimating
      the signal in single-trial recordings. Artifacts present a second problem. We
      will first review established methods of dealing with eye-movement artifacts and
      then propose an alternative. We will also report on current work on the
      parametrisation of single-trial signal estimates, which constitute the third
      problem considered.

PMID- 8579800
TI  - Methodological problems and clinical relevance of structural neuroimaging in
      dementia research.
AB  - Structural neuroimaging and dementia are conceptually different being only
      loosely correlated. Computed tomography or magnetic resonance imaging can never
      "prove" a clinical syndrome such as dementia, but yield clues as to its cause and
      the site and extent of pathological changes. Conversely, the type and degree of
      intellectual deterioration can hardly predict neuroradiological findings. The
      value of structural neuroimaging lies in detecting or excluding possible causes
      of dementia and quantifying linear or volumetric parameters of tissue and fluid
      volume. If based on a presumed or established etiology, however, specific
      neuropsychological and dementia syndromes may correspond to focal pathological
      changes seen in well-defined cerebral areas as recent investigations have shown
      with hippocampal atrophy in Alzheimer's dementia.

PMID- 8579801
TI  - Neuroimaging in alcoholism: CT and MRI results and clinical correlates.
AB  - For more than a century we have known the deleterious effects of alcohol on the
      brain regions surrounding the third ventricle and on the cerebellum. But it was
      only recently that we gained clearer evidence that the cortex is affected as
      well. Our imaging studies show that brain shrinkage is at least partially
      reversible once abstinence is maintained. They confirm results obtained in
      different laboratories from all over the world. Although our data contradict the
      rehydration hypothesis and thus lend credence to the idea of regeneration and
      neuroplasticity, the nature of reversibility is still a matter of debate.

PMID- 8579802
TI  - Frequency domain source localization shows state-dependent diazepam effects in 47
      channel EEG.
AB  - The topic of this study was to evaluate state-dependent effects of diazepam on
      the frequency characteristics of 47-channel spontaneous EEG maps. A novel method,
      the FFT-Dipole-Approximation (Lehmann and Michel, 1990), was used to study
      effects on the strength and the topography of the maps in the different frequency
      bands. Map topography was characterized by the 3-dimensional location of the
      equivalent dipole source and map strength was defined as the spatial standard
      deviation (the Global Field Power) of the maps of each frequency point. The
      Global Field Power can be considered as a measure of the amount of energy
      produced by the system, while the source location gives an estimate of the center
      of gravity of all sources in the brain that were active at a certain frequency.
      State-dependency was studied by evaluating the drug effects before and after a
      continuous performance task of 25 min duration. Clear interactions between drug
      (diazepam vs. placebo) and time after drug intake (before and after the task)
      were found, especially in the inferior-superior location of the dipole sources.
      It supports the hypothesis that diazepam, like other drugs, has different effects
      on brain functions depending on the momentary functional state of the brain. In
      addition to the drug effects, clearly different source locations and Global Field
      Power were found for the different frequency bands, replicating earlier reports
      (Michel et al., 1992).

PMID- 8579803
TI  - D2-receptor imaging with [123I]IBZM and single photon emission tomography in
      psychiatry: a survey of current status.
AB  - D2-dopamine receptors can be visualized in the human brain in vivo by Single
      Photon Emission Tomography (SPECT) and the radiolabeled benzamide [123I]IBZM. The
      present paper reviews the current status of this type of functional brain imaging
      with respect to basic methodological aspects, data analysis and quantification.
      The results from published clinical studies in different psychiatric patient
      populations and normal controls with [123I]IBZM are reviewed. [123I]IBZM-SPECT is
      a powerful tool for the investigation of D2-dopamine receptor status in
      psychiatric disorders, different types of drug treatment as well as therapeutic
      and side effects of pharmacologic agents. However, there still is a need for
      standardized imaging times and image-processing procedures. Advantages and
      disadvantages of SPECT with special regard to Positron Emission Tomography (PET)
      are also discussed.

PMID- 8579804
TI  - Single photon emission tomography (SPET) imaging of dopamine D2 receptors in the
      course of dopamine replacement therapy in patients with nocturnal myoclonus
      syndrome (NMS).
AB  - Single photon emission tomography (SPET) permits the in vivo measurements of
      regional cerebral radioactivity in the human brain following the administration
      of compounds labeled with photon-emitting isotopes. According to our SPET
      findings of a reduced binding of [123I]labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1
      ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) (a highly selective CNS D2 dopamine
      receptor ligand) to D2 dopamine receptors in striatal structures in untreated
      patients with nocturnal myoclonus syndrome (NMS) it seemed to be of interest to
      investigate whether there are changes in D2 receptor binding under dopamine
      replacement therapy or not. We studied the uptake and distribution of [123I]IBZM
      before and in the course of dopamine replacement therapy in four patients with
      severe insomnia caused by a nocturnal myoclonus syndrome (NMS). We found an
      increase of the IBZM binding to D2 receptors in the course of treatment, which
      was associated with an improvement of sleep quality. Reasons for this are
      discussed. The [123I]IBZM SPET technique in conclusion offers an intersting tool
      for in vivo investigations of functional changes in the dopaminergic
      neurotransmitter system in longitudinal studies.

PMID- 8579805
TI  - 99mTc-HMPAO-SPECT in the diagnosis of senile dementia of Alzheimer's type--a
      study under clinical routine conditions.
AB  - This study was designed to evaluate, whether investigations of cerebral blood
      flow can be a helpful diagnostic tool in the differential diagnosis between
      (senile) dementia of Alzheimer's type [(S)DAT] and geriatric depression with
      cognitive impairment. Under clinical routine conditions we performed Single
      Photon Emission Computed Tomography (SPECT) using 99mTc-Hexamethylpropyleneamine
      Oxime (HMPAO) in 23 patients with (S)DAT (14f, 9m; mean age 68.9 y), 17 patients
      with geriatric depression (9 f, 8 m; mean age 66.4 y) and 12 age-matched controls
      (9 f, 3 m; mean age 69.2 y). Semiquantitative analysis (corticocerebellar ratios)
      of eight different regions of interest (ROI) revealed a significantly (p < 0.05)
      reduced perfusion in the (S)DAT patients compared to the control group. The
      depression group exhibited perfusion values between the (S)DAT and control group.
      The difference between the depression and (S)DAT group was most prominent in the
      left parieto-occipital ROI (p = 0.008). We discuss the data with extensive regard
      to the literature and conclude that 99mTc-HMPAO SPECT is a valuable additional
      tool in the differential diagnosis of depression and dementia in the elderly.

PMID- 8579806
TI  - Larger topographical variance and decreased duration of brain electric
      microstates in depression.
AB  - The topographical configuration of the spontaneous brain electric fields is
      considered to contain relevant information about the pattern of the generating
      cortical electrochemical activation and the associated cognitive processes. Space
      oriented segmentation allows to break down the stream of the spontaneous EEG into
      brain electric microstates with stable configuration of the fields. It has been
      shown that the mean duration of the microstates was consistent with the duration
      of elementary steps of cognitive processes, and that different topographies of
      the microstates are associated with different cognitive modalities. Space
      oriented segmentation was applied to the resting EEG of 22 depressive patients
      and of 22 controls. The topographical variance was larger, and the most prominent
      brain electrical microstates of the EEG epochs were significantly shorter in the
      depressive group than in controls. No differences were found for the shortest
      microstates. This result cannot be explained by group differences in the
      frequency domain of the EEG. No topographical differences were found between the
      microstates of depressives and those of controls. Based on previous results in
      healthy volunteers during spontaneous cognition and in schizophrenic patients,
      the findings indicate that formal aspects rather than the modalities of the
      stream of cognition are altered in depression. Automatic and schematic
      processing, and attentional deficits as described in depressive patients might
      account for the finding of less sustained brain electrical microstates.

PMID- 8579807
TI  - Correlation between cognitive brain function and electrical brain activity in
      dementia of Alzheimer type.
AB  - Psychometric tests which assess cognitive brain function in dementia disorders
      are partly prone to artifacts, e.g., the experience of the investigator and the
      cooperation of the patient influences the results. An objective way to assess the
      degree of cognitive disturbance could be to measure neuronal activity represented
      by the electrical brain activity. The aim of the present study was to investigate
      how well cognitive function in dementia assessed by psychometric tests correlates
      with electrical brain activity (EEG). Multichannel EEG data was reduced into 3-D
      intracerebral equivalent dipole EEG generators allowing a more convenient
      statistical data management and valid physiological data interpretation. 35
      patients suffering from dementia of Alzheimer type were investigated. An increase
      of dipole strength in the slow frequency bands, a more anterior equivalent dipole
      of alpha- and beta-activity, and a slowing of the EEG with increasing cognitive
      deterioration could be demonstrated. The results support the hypothesis that the
      amount of disturbance of cognitive function in dementia can be assessed by
      measuring the electrical activity of the brain.

PMID- 8579808
TI  - Reduced frontal and occipital lobe asymmetry on the CT-scans of schizophrenic
      patients. Its specificity and clinical significance.
AB  - Frontal and occipital lobe width were determined in the computed tomographic (=
      CT) scans of 135 schizophrenic patients, 158 neuropsychiatrically healthy and 102
      psychiatric control subjects, including patients with affective psychosis,
      neurosis and schizoaffective psychosis. Most healthy right handed subjects
      demonstrate a relative enlargement of the right frontal as well as left occipital
      lobe compared to the opposite hemisphere. These normal frontal and occipital lobe
      asymmetries were selectively reduced in schizophrenics (f.: 5%, p < .0005; o.:
      3%, p < .05), irrespective of the psychopathological subgroup. Schizophrenic
      neuroleptic non-responders revealed a significant reduction of frontal lobe
      asymmetry (3%, p < .05), while no correlation between BPRS-subscores and
      disturbed cerebral laterality could be detected. In sum the present study
      demonstrates disturbed cerebral lateralisation in schizophrenic patients
      supporting the hypothesis of interrupted early brain development in
      schizophrenia.

PMID- 8579809
TI  - Some methodological issues in neuroradiological research in psychiatry.
AB  - An outline is given of some of the methodological issues discussed in
      neuroradiological research on psychiatric illness. Strengths and shortcomings of
      magnetic resonance imaging (MRI) in depicting and quantifying brain structures
      are described. Temporal lobe anatomy and pathology are easily accessible to MRI,
      whereas limits on anatomical delineation hamper approaches to frontal lobe study.
      White matter hyperintense lesions are sensitively depicted by MRI, but
      specificity is limited. Distinction of vascular and primary degenerative dementia
      is considerably improved by CT and MRI analysis. Computed tomography (CT) and MRI
      have enhanced the understanding of treatable organic psychiatric disorders, e.g.,
      normal pressure hydrocephalus. Subcortical and white matter pathology has been
      replicated in CT and MRI studies of late-onset psychiatric disorders, clinical
      overlap with cerebrovascular disease or neurodegeneration may be of import.
      Transcranial sonography findings of brainstem structural change specific to
      unipolar depression may contribute to the understanding of affective psychoses.
      Magnetic resonance spectroscopy and functional MRI are likely to stimulate
      psychiatric research in the future.

PMID- 8579810
TI  - Disturbances of cerebrospinal fluid (CSF) circulation--neuropsychiatric symptoms
      and neuroradiological contribution.
AB  - The present study aimed at relating dementia, pseudo-neurasthenic and affective
      organic brain syndromes to underlying type of CSF flow disorder and to subsequent
      alteration of anatomy. T2*-weighted magnetic resonance imaging (MRI) in the
      midsagittal plane permitted an analysis of aqueductal CSF flow phenomena and
      hydrocephalus-induced elevation, thinning and dorsal impingement of the corpus
      callosum. Furthermore, the width of the third ventricle was measured on the
      transverse scout images. 72 patients with communicating hydrocephalus (increased
      aqueductal CSF pulsations) and 26 patients with aqueductal stenosis (absence of
      aqueductal flow phenomena) were compared with 22 controls. Dementia and affective
      disorders were distributed equally among both CSF flow subgroups whereas pseudo
      neurasthenic syndromes were observed more frequently in non-communicating
      hydrocephalus (p < 0.03). Alzheimer-type and multiinfarct dementia syndromes were
      found more frequently in communicating hydrocephalus whereas non-classifiable
      dementia showed some predilection for non-communicating hydrocephalus. Callosal
      height, area and third ventricular width did not predict affective or
      pseudoneurasthenic disorder whereas third ventricular width (p < 0.01) and
      callosal area (p < 0.05) discriminated between demented and non-demented
      patients. Dorsal impingement of the corpus callosum by the falx was a non
      specific finding.

PMID- 8579811
TI  - EEG reactivity and EEG activity in never-treated acute schizophrenics, measured
      with spectral parameters and dimensional complexity.
AB  - Our approaches to the use of EEG studies for the understanding of the
      pathogenesis of schizophrenic symptoms are presented. The basic assumptions of a
      heuristic and multifactorial model of the psychobiological brain mechanisms
      underlying the organization of normal behavior is described and used in order to
      formulate and test hypotheses about the pathogenesis of schizophrenic behavior
      using EEG measures. Results from our studies on EEG activity and EEG reactivity
      (= EEG components of a memory-driven, adaptive, non-unitary orienting response)
      as analyzed with spectral parameters and "chaotic" dimensionality (correlation
      dimension) are summarized. Both analysis procedures showed a deviant brain
      functional organization in never-treated first-episode schizophrenia which,
      within the framework of the model, suggests as common denominator for the
      pathogenesis of the symptoms a deviation of working memory, the nature of which
      is functional and not structural.

PMID- 8579812
TI  - [Determining the duration of suspended license for alcohol intoxicated drivers].
AB  - Public safety on the road and the need of each individual to participate in road
      traffic call for drink drivers to be dealt with legally. They should be dealt
      with in a preventive, successful and individual manner. The insuperable
      difficulties encountered by a criminal judge when having to determine the type,
      extent and duration of the offence as well as determining the motivation for
      improvement, would justify the judge not having to determine the period of
      suspension as well. This could be achieved by introducing a minimum period of
      suspension for all offenders. For those interested in reacquiring their driving
      licence, directives should be imposed so that appropriate and individual steps
      can be taken right at the beginning of their suspension, in order that their
      suitability for road traffic can be restored. In that case Sunder's question
      asked at the beginning could be answered as follows: "The authority to withdraw
      driving licences should not be withdrawn from the judge."

PMID- 8579813
TI  - [Revoked driving right--a blunt weapon?].
AB  - I would like to complete and correct the article by Zabel in Blutalkohol XXXII
      (1995), 254 ff. by adding that the driving ban after speeding offences does not
      lead to a reduced risk of relapse. Furthermore, the standard federal list of
      offences punishable by fines is also valid in the Free State of Bavaria, and the
      principle of in dubio pro securitate is unknown in the German criminal law.

PMID- 8579814
TI  - [Ethanol-independent methanol elimination in chronic alcoholics].
AB  - 72% of a collective of chronic alcoholics (DSM-III-R, ICD 9), who were admitted
      under the influence of alcohol in order to undergo alcohol withdrawal, showed a
      serum methanol concentration (SMC) above 10 mg/l. This level is usually
      considered to be the one for the detection of regular alcohol consumption. The
      SMC values were considerably higher in cases where alcoholic beverages with a
      higher methanol content were consumed rather than the ones lower in methanol. In
      the majority of patients a decrease of the methanol concentration could only be
      detected once an individually varying limit concentration of ethanol (0-0.62
      g/kg) was reached. There were, however, a few exceptions where the elimination of
      methanol independent from the ethanol concentration could be seen. Contrasting
      the general collective, these 'ethanol independent' methanol eliminators showed a
      much higher serum level of ethanol and methanol at the time of admission. As a
      sign of addiction, all patients showed increased beta 60 values for ethanol and
      preferred high proof beverages, which at the same time have high methanol
      contents.

PMID- 8579815
TI  - [Congener analysis in a drinking trial with unusually high alcohol content].
AB  - The aforementioned case proves very convincingly that a very high dose of alcohol
      consumed within a short time span can be absorbed completely within 2 hours.
      Numerical models based on low to moderate alcohol consumption were lower than
      expected in cases of severe alcohol intake. The claim of alcohol consumption
      after an event can best be verified by means of a drinking experiment under
      intensive medical supervision.

PMID- 8579816
TI  - [Drinking trials for back calculation in long elapsed time intervals].
AB  - By evaluating 100 drinking experiments the formula put forward by Zink and
      Reinhardt for calculating the BAC at the time of the incident (maximum BAC = BAC
      at the time of blood sampling + 0.2/1000 per hour + 0.2/1000 added value for the
      first hour) was tested for its validity in cases when long time spans have to be
      taken into consideration. This evaluation showed that in cases of high BACs the
      elimination rate of ethanol during 8 or 9 was even higher than expected when the
      formula was applied. Even when increasing the additional value for the first hour
      to 0.3/1000, the calculated maximum BAC did not match the actual BAC measured in
      all cases.

PMID- 8579817
TI  - HPCE separation of protected amino acids and peptides.

PMID- 8579818
TI  - Heat shock proteins: applications in health and disease.
AB  - Heat shock proteins (hsps) assist the assembly, folding and translocation of
      other proteins, and apparently have a role in protecting cells against injuries
      and other types of stress. In addition, hsps are frequently recognized by the
      immune system as predominant antigens during infections and during the
      progression of certain autoimmune diseases and, thus, might provide a novel route
      for the development of immunotherapeutics. This review focuses on applications
      for hsps in health and disease, and discusses the pros and cons of considering
      them as targets for the development of therapeutics/pharmaceuticals.

PMID- 8579819
TI  - Alteration of complement activity: a strategy for xenotransplantation.

PMID- 8579820
TI  - Isolating and characterizing deep-sea marine microorganisms.
AB  - We have isolated several microorganisms that are adapted to living in the
      extremes of the deep-sea environment. They include barophilic bacteria, which are
      able to grow at high hydrostatic pressure, but that are unable to grow at
      atmospheric pressure, and organic-solvent-tolerant bacteria, which are able to
      grow in the presence of toxic organic solvents such as toluene or benzene. In
      this review, we describe how to isolate such extremophiles, and we outline the
      characteristics of several strains that have been recovered from the deep-sea
      environment.

PMID- 8579821
TI  - Combinatorial chemistry in the discovery and development of drugs.

PMID- 8579822
TI  - Conversion of oleic acid to 10-hydroxystearic acid by two species of ruminal
      bacteria.
AB  - Bacteria able to convert oleic acid to 10-hydroxystearic acid were isolated from
      the ovine rumen. The solid hydroxy fatty acid produced from bacterial
      fermentations containing oleic acid was recovered by filtration, extraction into
      ether and crystallisation. The identity of the product was confirmed by HPLC and
      gas chromatography/mass spectrometry. One 10-hydroxystearic-acid-producing
      bacterial group was represented by two strains of an anaerobic gram-negative
      curved rod with tufts of flagella on the concave surface of the cell. The
      morphology and other characteristics enabled the strains to be tentatively
      identified as Selenomonas ruminantium. Another bacterium capable of the same
      transformation, represented by two strains of a facultatively anaerobic gram
      positive chain-forming coccus, was identified as Enterococcus faecalis. Since
      unsaturated fatty acids entering the rumen are normally hydrogenated, hydration
      of oleic acid represents an alternative fate of unknown significance in vivo.

PMID- 8579823
TI  - A study of the substrate specificity of aminopeptidase N from Lactococcus lactis
      subsp. cremoris Wg2.
AB  - A systematic study was made of the ability of aminopeptidase N from Lactococcus
      lactis subsp. cremoris Wg2 to hydrolyse different peptide substrates. The enzyme
      showed a marked preference for substrates containing arginine as the N-terminal
      residue but, to a lesser extent, was also capable of cleaving other residues such
      as lysine and leucine. There was a tendency for the activity to increase with the
      hydrophobicity index of the C-terminal residue of dipeptide substrates. It was
      also observed that the enzyme tended to have higher affinities but lower Vmax
      values for tripeptides with hydrophobic C-terminal residues. The values
      determined for Km and Vmax increased with chain length for oligopeptides of the
      general formula Lys-Phe-(Gly)n, the optimum, as determined from Vmax/Km, being
      when n = 4. Typical Km values for the most effective substrates were in the range
      0.2-0.6 mM.

PMID- 8579825
TI  - Hyperproduction of a recombinant fusion protein of Staphylococcus aureus V8
      protease in Escherichia coli and its processing by OmpT protease to release an
      active V8 protease derivative.
AB  - The expression of a recombinant fusion protein including Staphylococcus aureus V8
      protease was studied by using Escherichia coli as the host strain. When the
      mature V8 protease was expressed as a fusion protein with a truncated E. coli
      beta-galactosidase (beta-gal97S4D), we could not obtain a sufficient amount of
      the enzyme because of the toxicity resulting from the expressed protease
      activity. Synthesis of V8 protease was increased by constructing a sandwich-type
      fusion protein consisting of beta-gal97S4D, a V8 protease derivative with the 56
      C-terminal amino acids deleted (V8 delta 56) and a truncated aminoglycoside-3'
      phosphotransferase. This fusion protein was successfully produced as inactive
      inclusion bodies. To release the V8 delta 56 protease from the fusion protein, we
      developed a novel processing method using an endogeneous E. coli OmpT protease,
      which can recognize the dibasic amino acid residues located in the linker
      peptides of the fusion protein. After solubilizing the inclusion bodies with
      urea, the V8 delta 56 protein was automatically released from the fusion protein
      by the OmpT protease, which was coprecipitated with the inclusion bodies. The V8
      delta 56 protease thus obtained showed the same enzymatic activity as that of the
      native V8 protease. We demonstrate in this study that the N-terminal prepro
      sequence and the C-terminal repeated sequence of this enzyme are not necessary
      for its enzymatic activity and protein folding.

PMID- 8579824
TI  - Purification and characterization of an arabinofuranosidase from Bacillus
      polymyxa expressed in Bacillus subtilis.
AB  - Two polypeptides showing alpha-L-arabinofuranosidase activity have been purified
      to homogeneity from culture supernatants of a Bacillus subtilis clone harbouring
      the xynD gene [Gosalbes et al. (1991) J Bacteriol 173: 7705-7710] from Bacillus
      polymyxa. Both polypeptides, with determined molecular masses of 64 kDa and 53
      kDa, share the same sequence at their N termini, which also coincides with the
      sequence deduced for the mature protein from the previously determined sequence
      of nucleotides (Gosalbes et al. 1991). The two polypeptides have been
      biochemically characterized. Arabinose is the unique product released from
      arabinose-containing xylans which are substrates for both enzyme forms. Other
      natural arabinose-containing polysaccharides, such as arabinogalactans, are not
      attacked by them but some artificial arabinose derivatives are good substrates
      for both polypeptides. Their arabinose-releasing activity on arabinoxylans
      facilitates the hydrolysis of the xylan backbone by some endoxylanases from
      Bacillus polymyxa.

PMID- 8579826
TI  - Effects of growth environment on recombinant plasmid stability in Saccharomyces
      cerevisiae grown in continuous culture.
AB  - A recombinant strain of Saccharomyces cerevisiae, containing a 2-microns-fragment
      based plasmid (pYE alpha a4) was grown under non-selective conditions in
      continuous culture. The decrease in the population carrying the plasmid-encoded
      auxotrophic marker, LEU2, was examined under different physiological conditions.
      The difference in growth rate (delta mu) between plasmid-free and plasmid
      containing cells and the rate of plasmid segregation (R) were determined using a
      non-linear regression technique. Loss rates were greater in defined glucose
      limited cultures than in complex glucose-limited cultures. Plasmid loss was delta
      mu-dominated in cultures grown on defined media whereas delta mu and R were co
      dominant in cultures grown on complex medium. Loss rates increased with
      increasing dilution rate in complex glucose-limited cultures. The reverse was
      found in defined glucose-limited cultures. Plasmid retention and loss kinetic
      determined from defined magnesium-limited cultures were not significantly
      different from those observed in defined glucose-limited cultures. Although
      plasmid retention in defined phosphate-limited culture was not significantly
      different from that in defined glucose-limited culture, reduced R and increased
      delta mu indicated an alternative physiological effect of phosphate limitation on
      plasmid stability.

PMID- 8579827
TI  - Characteristics of Tn5307 exchange and intergeneric transfer of genes associated
      with nisin production.
AB  - Transfer of the Lactococcus lactis 11454 nisin-sucrose conjugative transposon,
      Tn5307, was investigated to develop a methodology for conjugation of this element
      to other lactic acid bacteria. Tn5307 exchange was sensitive to temperature and
      pH but was not affected by protease or amylase treatments to donor cells.
      Moreover, conjugation studies demonstrated that the direct-plate method could be
      employed to rapidly identify LM2301 transconjugants able to transfer Tn5307 at
      least ten times more efficiently than 11454. Intergeneric transfer of nisin and
      sucrose genes between L. lactis and a dairy Enterococcus sp. was also
      investigated. Erythromycin-resistant Enterococcus sp. recipients were developed
      by electro-transformation with pGK13 or by conjugal introduction of the broad
      host-range plasmid pAM beta 1. Matings between L. lactis 11454 and an
      Enterococcus sp. recipient that contained pAM beta 1 yielded sucrose-positive,
      nisin-immune transconjugants at a frequency of 2.3 x 10(-9) transconjugants per
      donor cfu. Agar-overlay assays for nisin production revealed that enterococcal
      transconjugants did not produce the bacteriocin, but DNA.DNA hybridization with a
      nisA-specific probe demonstrated that these bacteria had acquired the nisin
      structural gene.

PMID- 8579828
TI  - Efficient expression and secretion of Aspergillus niger RH5344 polygalacturonase
      in Saccharomyces cerevisiae.
AB  - An Aspergillus niger endopolygalacturonase (EC 3.2.1.15) cDNA was expressed in
      the yeast Saccharomyces cerevisiae. Secretion of the protein into the growth
      medium was efficiently directed by the fungal leader sequence, and processing
      occurred at the same site as in Aspergillus. The expression level was
      significantly enhanced by using a "short" version of the yeast ADHI promoter. An
      additional increase in the yield of heterologous protein was due to a higher
      plasmid stability and a rise in plasmid copy number. This was achieved by
      deleting most of the bacterial sequences from the expression vector. The yeast
      derived enzyme showed the same enzymatic and biochemical properties as the fungal
      polygalacturonase, such as substrate specificity, pH and temperature optima and
      pI value. The yeast-derived enzyme, however, showed a higher degree of
      glycosylation and exhibited a more pronounced temperature stability than the
      fungal enzyme.

PMID- 8579829
TI  - Heterologous protein secretion by Aspergillus niger growing in submerged culture
      as dispersed or aggregated mycelia.
AB  - The secreted production of a heterologous enzyme, hen egg-white lysozyme, by
      Aspergillus niger was studied in shake flasks containing media of different
      initial viscosities. Raising the viscosity of the medium by addition of
      polyvinylpyrrolidone (PVP) brought about a transition in the form of growth from
      aggregated mycelia (pellets) to dispersed mycelia. The specific yield of lysozyme
      in cultures containing an initial concentration of 5% (w/v) starch was 8 mg
      lysozyme/g dry weight. Addition of 2% (w/v) PVP to the medium resulted in a
      specific yield of 14 mg lysozyme/g dry weight.

PMID- 8579830
TI  - The cellulase system of the anaerobic rumen fungus Neocallimastix frontalis:
      studies on the properties of fractions rich in endo-(1-->4)-beta-D-glucanase
      activity.
AB  - Seven fractions rich in endoglucanase activity were separated from the
      extracellular cellulase system of the anaerobic rumen fungus Neocallimastix
      frontalis. The fractions (ES1, ES3, ES2U1, ES2U2, ES2U4, ES2U3C1 and ES2U3C2)
      were separated from each other and from a fraction that could solubilize
      crystalline cellulose (the so-called crystalline-cellulose-solubilizing
      component, CCSC) by the sequential use of differential adsorption on the
      microcrystalline cellulose Avicel, gel filtration and affinity chromatography on
      concanavalin-A-Sepharose. The molecular masses of the endoglucanase fractions,
      when determined by gel filtration, were 64, 30, 61, 113, 17, 38 and 93 kDa
      respectively. Each enzyme degraded carboxymethylcellulose and was rich in
      activity to cellulose swollen in phosphoric acid to break the hydrogen bonding:
      cellobiose, cellotriose and cellotetraose were released in differing proportions.
      Each fraction showed a characteristic gradient when the capacity of each enzyme
      to increase the fluidity of a solution of carboxymethylcellulose was plotted
      against the increase in reducing power of the solution. Although neither
      endoglucanase fraction, acting in isolation, could degrade crystalline cellulose,
      three of the fractions (ES1, ES3 and ES2U1) could act synergistically with the
      CCSC fraction in this regard. Remarkably, the same three fractions also acted in
      synergism with the cellobiohydrolases (CBH I and CBH II) of the aerobic fungus
      Penicillium pinophilum in degrading crystalline cellulose, but only when both
      cellobiohydrolase enzymes were present in the solution along with any one of the
      three endoglucanases. These observations support the conclusion that the
      mechanism of action of the cellulase system of N. frontalis in degrading
      crystalline cellulose may be similar to that operating in the aerobic fungi.

PMID- 8579831
TI  - Effects of enhanced lysine epsilon-aminotransferase activity on cephamycin
      biosynthesis in Streptomyces clavuligerus.
AB  - A recombinant strain of S. clavuligerus (LHM100) that contains an additional copy
      of the gene (lat) encoding lysine epsilon-aminotransferase (LAT) was analyzed and
      compared to the wild-type for intracellular concentrations of primary metabolites
      involved in cephamycin C biosynthesis. This strain had been shown previously to
      produce higher levels of the antibiotic because of increased levels of LAT, a
      rate-limiting enzyme involved in the production of alpha-aminoadipic acid. The
      results showed that the overall growth kinetics of the two strains were
      comparable, including the intracellular concentrations of cysteine, valine and
      lysine. In contrast, 60% higher antibiotic production was observed in LHM100,
      which reflected a significant temporal variation in specific metabolite
      production rate. The time profile of LAT activity was consistently higher in
      LHM100; however, alpha-aminoadipic acid levels showed unexpected variation during
      the growth cycle. These results support the proposal that rate-limiting enzymes
      in cephamycin C biosynthesis are temporally controlled, and indicate that
      optimization of metabolite production will require differential overexpression of
      several biosynthetic genes.

PMID- 8579832
TI  - Epinigericin toxicity towards Tetrahymena pyriformis GL; changes in cell volume
      and intracellular pH.
AB  - A study of the toxicity of epinigericin, an antibiotic ionophor, towards the
      ciliate Tetrahymena pyriformis showed that this molecule stopped cell division,
      increased cell volume and led to a more basic intracellular pH. The action of
      epinigericin was probably linked to its function as an ionophor. The ionic
      selectivity of this molecule is still not known. The raising of the intracellular
      pH of ciliates by this antibiotic may be linked to its toxic action and its
      iontransport mechanism in Tetrahymena.

PMID- 8579833
TI  - Soil management enhancing hydrocarbon biodegradation in the polluted Kuwaiti
      desert.
AB  - Oil-polluted Kuwaiti desert samples, exposed to the open air, were subjected to
      specific types of management, once every 2 weeks, throughout a year; control
      samples were not treated. The total amounts of extractable alkanes from the
      control samples remained fairly constant during the dry hot months, but decreased
      during the rainy months reaching, after 1 year, slightly more than one-half of
      the amount at zero time. This result demonstrates the self-cleaning of the
      Kuwaiti desert and the essential role of moisture in this process. Out of the
      eight types of management studied, the repeated fertilization of the polluted
      sample with 3% KNO3 solution was most efficient, reducing the extractable alkanes
      after 1 year to about one-third of zero reading. Repeated fertilization with
      treated sewage effluent was inhibitory to alkane biodegradation, probably because
      of increasing soil acidity. The latter inhibitory effect was annulled by liming.
      Repeated irrigation with 3% NaCl solution was inhibitory, but 1% NaCl solution
      slightly promoted alkane biodegradation. The various samples contained 10(10)
      10(11) oil-utilizing bacteria/g soil, predominantly Bacillus, Pseudomonas,
      Rhodococcus and Streptomyces. Oil-utilizing fungi were much less frequent and
      were predominantly Aspergillus and Penicillium species. The microbial numbers
      varied not only according to the type of soil management but also to the season.

PMID- 8579834
TI  - Intracellular flux analysis applied to the effect of dissolved oxygen on
      hybridomas.
AB  - Quantitative estimates of intracellular fluxes and measurements of intracellular
      concentrations were used to evaluate the effect of dissolved oxygen (DO)
      concentration on CRL 1606 hybridoma cells in batch culture. The estimates of
      intracellular fluxes were generated by combining material balances with
      measurements of extracellular metabolite rates of change. Experiments were
      performed at DO levels of 60% and 1% air saturation, as well as under oxygen
      limited conditions. Cell extracts were analyzed to evaluate the effect of DO on
      the intracellular concentrations of the glutamate dehydrogenase reactants, as
      well as the redox state of the pyridine nucleotides in the cytosol and
      mitochondria. The relationship between cell density and pyridine nucleotide redox
      state was also investigated. Dissolved oxygen concentration had a significant
      effect on nitrogen metabolism and the flux through glutamate dehydrogenase was
      found to reverse at low DO, favoring glutamate formation. The NAD in the cytosol
      and mitochondria was more reduced under low DO conditions while the cytosolic NAD
      was more oxidized at low DO. Cytosolic NAD was reduced at higher cell densities
      while the redox states of cytosolic NADP and mitochondrial NAD did not exhibit
      significant variation with cell density. These results point to the fundamental
      role of the intracellular oxidation/reduction state in cell physiology and the
      possibility of controlling physiological processes through modulation of the
      dissolved oxygen level or the oxidation/reduction potential of the culture.

PMID- 8579835
TI  - Degradation of stachyose, raffinose, melibiose and sucrose by different tempe
      producing Rhizopus fungi.
AB  - Forty-six strains of tempe-forming Rhizopus species were screened for their
      ability to grow on raffinose as the sole carbon source. Six of the strains showed
      good growth and sporulation. These isolates were one Rhizopus oligosporus, one
      Rhizopus microsporus var. chinensis, three Rhizopus oryzae and one Rhizopus
      stolonifer. These six moulds and R. oligosporus strain NRRL 2710 were
      investigated for their metabolism of the raffinose family of alpha-galactoside
      carbohydrates. Degradation experiments were performed in submerged culture in a
      medium containing soybean alpha-protein, sodium phytate and either stachyose,
      raffinose or melibiose. R. oryzae and R. stolonifer completely consumed the
      tested carbohydrates as carbon source. R. microsporus var. chinensis failed to
      hydrolyse the alpha-galactosidic bonds of raffinose, stachyose or melibiose,
      whereas it was able to use sucrose and the fructose moiety of raffinose or
      stachyose for growth. R. oligosporus NRRL 2710 was unable to hydrolyse any of the
      tested carbohydrates. The results of the oligosaccharide degradation experiments
      could be verified during tempe production from soybeans with the selected fungal
      species.

PMID- 8579836
TI  - Improved yields of the extracellular domain of the epidermal growth factor
      receptor produced using the baculovirus expression system by medium replacement
      following infection.
AB  - The extracellular domain of the epidermal growth factor receptor (EGFR) was
      expressed using the baculovirus expression vector system. The maximum level of
      the EGFR extracellular domain secreted into the medium in Sf-9 (Spodoptera
      frugiperda or fall army-worm) cell batch culture was approximately 2.5 micrograms
      ml-1. In order to increase this yield, a process was developed that included the
      following sequence of steps: batch growth to maximum cell density, infection of
      the cells with recombinant virus, and replacement of spent medium. By using this
      process, the specific yield of recombinant protein, which in batch culture drops
      when infection is carried out at densities greater than 3 x 10(6) cells ml-1, can
      be maintained at a maximum in cultures infected at densities of 10(7) cells ml-1
      or greater. The process, when applied to 3-1 and 11-1 bioreactor cultures,
      allowed a maximum volumetric yield of triple the maximum value attainable in
      batch culture. Spent-medium analysis indicates that medium replacement provides
      certain nutrients that could otherwise be limiting for recombinant protein
      production.

PMID- 8579838
TI  - Identification of new enzyme activities of several strains of Thermus species.
AB  - New thermostable enzyme activities of seven Thermus strains were compared using
      the API ZYM system. All the strains exhibited high levels of alpha- and beta
      glycosidases, esterase (C4) and esterase-lipase (C8) activities intracellularly.
      Only T. thermophilus HB8 (ATCC 27634) showed alpha-glucosidase and esterase
      activities in the supernatant. According to the intensity of beta-galactosidase
      activity, Thermus strains were divided in three groups. Group 0, which showed a
      weak beta-galactosidase activity, included Thermus spp. ATCC 31674 (T351) and
      27978 (X-1) as well as T. thermophilus ATCC 27634 (HB8). Group I which consisted
      of T. aquaticus ATCC 25104 (YT-1), ATCC 25105 (Y-VII-51B) and Thermus sp. ATCC
      27737 (T2), had a specific activity of approximately 40.0 U mg-1 and galactose as
      inducer. T. aquaticus ATCC 31558 (group 2) was particularly effective for beta
      galactosidase production (2840 U) with a specific activity of 98 U mg-1. For each
      strain, galactose (0.5%) was a better inducer of beta-galactosidase production
      than lactose (1%). The detection of beta-galactosidase activity was dependent on
      the derivative chromogenic substrates used (naphthyl or nitrophenol coupled to
      sugar). Oligosaccharides were synthesized from cellobiose, lactulose, maltose or
      lactose as substrates at high temperature in some strains of Thermus.

PMID- 8579837
TI  - CMP-N-acetyl neuraminic-acid synthetase from Escherichia coli: fermentative
      production and application for the preparative synthesis of CMP-neuraminic acid.
AB  - In an optimized sorbitol/yeast extract/mineral salt medium up to 12 U/l CMP-N
      acetyl-neuraminic-acid (Neu5Ac) synthetase was produced by Escherichia coli K-235
      in shake-flask culture. A colony mutant of this strain, E. coli K-235/CS1, was
      isolated with improved enzyme formation: in shake flasks with a yield of up to
      20.8 U/l and 54 mU/mg protein in the cell extract. With this strain 26500 U CMP
      Neu5Ac synthetase was produced with a high specific activity (0.128 U/mg) by fed
      batch fermentation on 230-l scale. On a 10-1 scale the enzyme yield was 191 U/l
      culture medium. The enzyme was partially purified by precipitation with
      polyethyleneglycol resulting in a three- to fourfold enrichment and a recovery
      rate of more than 80%; most of the CTP hydrolysing enzymes were removed. The
      native synthetase was deactivated completely by incubation at 45 degrees C for 10
      min, but could be stabilized remarkably by glycerol and different salts. The
      enzyme was used for the preparative synthesis of CMP-Neu5Ac with a conversion
      yield of 87% based on CTP.

PMID- 8579839
TI  - Rabbit whey acidic protein gene upstream region controls high-level expression of
      bovine growth hormone in the mammary gland of transgenic mice.
AB  - Transgenic mice were produced which secreted high levels of bGH into milk. The
      6.3-kb upstream region of the rabbit whey acidic protein (rWAP) gene was linked
      to the structural part of the bovine growth hormone (bGH) gene, and the chimeric
      gene was radioimmunoassay into mouse oocytes. bGH was detected by
      radioimmunoassay in the milk of all resulting transgenic mice. bGH concentrations
      in milk varied from line to line, from 1.0-16 mg/ml. This expression was not
      correlated to the number of transgene copies. In all lines studied, the mammary
      gland was the major organ expressing bGH mRNA during lactation. bGH mRNA
      concentrations were barely detectable in the mammary gland of cyclic females;
      they increased during pregnancy. These results show that the upstream region of
      the rWAP gene harbors powerful regulatory elements which target high levels of
      bGH transgene expression to the mammary gland of lactating transgenic mice.

PMID- 8579840
TI  - Messenger RNA encoding an estrogen-dependent oviduct secretory protein in the
      sheep is localized in the apical tips and basal compartments of fimbria and
      ampulla epithelial cells implying translation at unique cytoplasmic foci.
AB  - Data from our laboratory have shown that an estrogen (E2)-dependent M(r) 90,000
      92,000 protein and its mRNA are synthesized and expressed in abundant amounts at
      estrus from the fimbria and ampulla, not isthmus, oviduct of the sheep.
      Immunocytochemical studies have shown that the M(r) 90,000-92,000 protein is
      contained in apical secretory granules of oviduct epithelial cells. The objective
      of this study was to determine whether the mRNA for the E2-dependent oviduct
      protein was localized and compartmentalized in similar manner. Fimbria, ampulla,
      and isthmus oviducts obtained from estrous ewes were flash frozen in liquid
      nitrogen, cryosectioned, fixed in 4% paraformaldehyde, hybridized with
      digoxigenin (DIG)-labeled oviduct-specific riboprobes, incubated in anti-DIG
      antibodies conjugated with alkaline phosphatase, and developed in color
      substrate. Oviduct protein-specific transcripts were localized to basal
      perinuclear compartments and, surprisingly, at sites distant from the nucleus in
      the apical cytoplasm of epithelial cells in the fimbria and ampulla. No specific
      reaction product was observed in the underlying mucosa or smooth muscle layers.
      Oviduct protein mRNA was contained predominantly in the apical cytoplasm of
      epithelial cells at the free margins of mucosal folds and in the basal regions of
      cells located at the crypts of longitudinal folds. No reaction product was
      present when sections of the fimbria and ampulla oviduct of estrous ewes were
      incubated in sense riboprobe to the oviduct protein. In addition, when sections
      of the isthmus oviduct obtained from estrous ewes or fimbira and ampulla oviducts
      from long-term ovariectomized ewes were hybridized with antisense riboprobes no
      specific reaction product was detected. Electron microscopy of oviduct protein
      mRNA containing areas revealed the presence of secretory granules, rough
      endoplasmic reticulum (RER) and Golgi in the apical cytoplasm, and RER in the
      basal regions of epithelial cells. These data show that the mRNA encoding an E2
      dependent oviduct-specific protein is distributed in epithelial cells at
      perinuclear foci and at sites distant from the nucleus, which are also the sites
      of protein localization and protein synthesizing organelles, implying translation
      at unique cytoplasmic foci.

PMID- 8579842
TI  - Gene transfer and expression in mouse preimplantation embryos by recombinant
      adenovirus vector.
AB  - Replication-defective recombinant adenovirus, Adex4SRLacZL, was used as a vector
      for transferring exogenous genes in mouse zona pellucida-free eggs at the
      pronuclear stage. The vector contained the E. coli LacZ reporter gene under the
      control of the SR alpha promoter (SV40 early promoter-fused HTLV-I LTR), and the
      expression of the reporter gene was examined during preimplantation development
      in culture. Histochemical staining of the embryos for beta-galactosidase activity
      showed that the exogenous LacZ gene as expressed in 98% of the embryos at the
      morula-blastocyst stages. As in the microinjection method, the exogenous genes
      could be pursued from the 2-cell stage. Neither apparent morphological changes
      nor cytotoxic effects were observed. Both the percentages of embryos expressing
      reporter genes and the rate of development to the blastocyst stage were higher in
      the adenovirus vector-treated embryos than in the microinjected ones. These
      results suggest that the adenovirus vector system is a useful tool in
      investigating the genetic control of early mammalian development.

PMID- 8579843
TI  - Initiation of transcription and nucleologenesis in equine embryos.
AB  - The time of activation of the embryonic genome (maternal-embryonic transition) in
      equine embryos was investigated by assessing incorporation of 3H-uridine and
      nucleolar development. In Experiment 1, embryos were recovered from the oviduct
      (n = 15) and the uterus (n = 3). Recovered embryos were assessed for morphologic
      development and quality score. Recovered embryos with less than 8 cells (two
      cells, n = 4; four cells, n = 5; five cells, n = 2) were incubated with 3H
      uridine (560 microCi/ml) for 10 hr, while eight-cell embryos (n = 2), morulae (n
      = 2), and blastocysts (n = 3) were incubated with 280 microCi/ml for 0.5-1 hr. At
      the end of incubation, embryos were washed twice in PBS with 10% FBS and
      incubated for 30 min with 2.5 mg/ml of unlabelled uridine. Embryos were spread
      onto glass slides, dipped into emulsion, and exposed for 8 d, then developed and
      counterstained with Giemsa and propidium iodide. Embryos at the blastocyst,
      morula, eight-cell, and five-cell stages incorporated 3H-uridine into their cell
      nuclei as detected by autoradiography. In a second experiment, nucleologenesis in
      equine embryos was examined by transmission electron microscopy. Nucleoli or
      nucleolar precursors were found in 12 of 23 embryos examined. Most embryos in the
      four- to six-cell stage (n = 7) had nucleolar precursor bodies (npb) consisting
      of homogeneous fibrillar structures. Two five- to six-cell embryos also possessed
      reticulated nucleoli with both fibrillar and granular components as did all eight
      cell embryos (n = 3). Nucleoli in one morula and one blastocyst were reticulated
      with prominent granular components, fibrillar components, and apparent fibrillar
      centers. These results indicate that incorporation of 3H-uridine and the
      formation of functional nucleoli with typical fibrillar and granular components
      occurs between the four- to eight-cell stage in equine embryos.

PMID- 8579841
TI  - 5-Aza deoxyCytidine-induced inhibition of differentiation of spermatogonia into
      spermatocytes in the mouse.
AB  - In order to explore the significance of DNA methylation in proliferation and
      differentiation of germ cells in testis, 5-aza,2'-deoxyCytidine (5-azaCdR), a
      hypomethylating agent, was administered in vivo to neonatal mice having only
      spermatogonial (premeiotic) cells. End-labeling of the MspI, HpaII, and HhaI
      digested DNA revealed considerable loss of methylation following the treatment.
      Cellular and histological preparations of the testis showed complete inhibition
      of differentiation into spermatocytic stage. Analysis of protein synthesis in the
      treated and control testis by growing the cells in 35S-Methionine medium and
      resolving the lysate by SDS-PAGE revealed that the programme of expression of at
      least 5 polypeptides (35.0, 31.5, 27.0, 22.5, and 18.0 KD) was altered as a
      result of 5-azaCdR incorporation. It appears that DNA methylation plays a
      critical role in the differentiation of gonia into primary spermatocytes.

PMID- 8579844
TI  - Kit ligand mediates survival of type A spermatogonia and dividing spermatocytes
      in postnatal mouse testes.
AB  - In the mouse testis, spontaneous death of spermatogonia has a large impact on the
      output of differentiating spermatids. The tyrosine kinase receptor c-kit is
      expressed in type A, intermediate, and B spermatogonia, and kit-ligand (KL) is
      expressed in Sertoli cells. Previous work indicated a depletion of type A
      spermatogonia after in vivo exposure to an antibody that blocks c-kit function.
      The present work was undertaken to determine whether blocking c-kit function
      results in apoptosis of spermatogonia or in an inability of spermatogonia to
      proliferate. Testes sections were stained by a method that detects apoptotic
      cells in situ. In testes of 8-day postnatal (P8) males, type A spermatogonia are
      the predominant germ cell type present. Stained sections from P8 males injected
      with the c-kit antagonistic antibody ACK2 showed a fivefold higher rate of cell
      death than uninjected controls. At least a twofold increase was observed in P12
      and P30 injected males and in P30 SId/+ males as compared to uninjected controls.
      Determination of the stage of germ cell development that was affected in P30
      males indicated that the frequency of gonial cell death was increased fourfold,
      but the frequency of death in spermatocytes around the time of the meiotic
      division was increased 15-fold. It is concluded that KL acts to prevent apoptosis
      in the testis in vivo, that the membrane bound form of KL may be more effective,
      and that survival of late meiotic and dividing spermatocytes is regulated by KL
      through an indirect mechanism probably mediated by Sertoli cells. Thus, KL is an
      important regulator of spermatid output.

PMID- 8579845
TI  - Mechanism of action of epidermal growth factor-induced porcine oocyte maturation.
AB  - EGF has been reported to promote oocyte maturation in several species, although
      the mechanism of action is not yet known. The present study is designed to
      determine the pathway used by EGF to enhance porcine oocyte maturation. Oocytes
      were aspirated from 2-5 mm follicles and cultured with various treatments in
      Medium-199 at 37 degrees C, 100% relative humidity, and 5% CO2 for 48 hr for the
      maturation study and 3 hr for intracellular cAMP measurement. Although treatment
      with 100 IU/ml hCG stimulated both intracellular cAMP formation and oocyte
      maturation, 10 ng/ml EGF stimulated oocyte maturation only. Dibutyryl cAMP
      (dbcAMP) inhibited oocyte maturation at 10(-5), 10(-4), and 10(-3) M
      concentration s in the control medium. However, in the presence of 10 ng/ml EGF,
      dbcAMP inhibited oocyte maturation only at a concentration of 10(-3) M.
      Increasing concentrations of EGF (i.e., 25 and 50 ng/ml) were ineffective in
      overcoming the inhibitory effect of dbcAMP at 10(-3) M. In contrast, EGF reversed
      the decreased maturation rate caused by transforming growth factor-beta. Phorbol
      myristate acetate (PMA), a tumor-promoting phorbol ester, enhanced the
      spontaneous maturation rate; 4 alpha-phorbol dideconoate, an inactive phorbol
      ester, did not show this effect. PMA- and EGF-stimulated porcine oocyte
      maturation is reversed by calphostin-C, a PKC inhibitor. In conclusion, EGF's
      promotional activity on porcine oocyte maturation is independent of the cAMP
      pathway and probably mediated by the PKC pathway.

PMID- 8579846
TI  - Capacitation in vitro of bovine spermatozoa by oviduct epithelial cell monolayer
      conditioned medium.
AB  - The effect of the active capacitating factor secreted from oviduct epithelial
      cell monolayers (OECM) in different environments on in vitro fertilization was
      evaluated. Capacitation was determined as the ability of sperm to fertilize
      bovine oocytes in vitro. When the mTALP was supplemented with glucose during
      conditioning, the sperm penetration rate was significantly reduced (P < 0.05)
      compared to the control (7% +/- 1 vs. 30% +/- 4). The percentages of sperm
      penetrated oocytes were higher following insemination in the OECM-conditioned
      medium derived from the early stage (48% +/- 7) of the estrous cycle than in the
      OECM-conditioned medium derived from either mid (35% +/- 2) or late stages (28%
      +/- 3) of the estrous cycle. When the medium was supplemented with 0.1 or 0.5
      microgram/ml estradiol-17 beta during medium conditioning, sperm penetration
      rates increased (P < 0.05) compared to the control group (55% +/- 4 vs. 40% +/- 3
      and 54% +/- 2 vs. 41% +/- 3, respectively). In addition, the percentages of
      penetrated oocytes significantly decreased (P < 0.05) following insemination when
      the OECM-conditioned medium was added to 0.01%, 0.05%, and 0.1% ethanol compared
      to the control (25% +/- 4, 19% +/- 2, 18% +/- 3, and 45% +/- 3, respectively).
      Sperm penetration rates significantly (P < 0.01) decreased when the OECM
      conditioned medium was heated to 100 degrees C for 5 min (10% +/- 1 vs. 40% +/-
      3). These results suggest that the active capacitating factor was secreted by the
      OECM and that this capacitating factor in the OECM-conditioned medium was
      inhibited by the presence of glucose. This factor was found to be heat-sensitive
      and its action was affected by ethanol. The OECM derived from the three phases of
      the estrous cycle as well as the presence of estradiol-17 beta influenced the
      capacity of the OECM to secrete this capacitating factor in vitro.

PMID- 8579847
TI  - Intracellular calcium reaches different levels of elevation in hyperactivated and
      acrosome-reacted hamster sperm.
AB  - Calcium plays a role in sperm motility hyperactivation and the acrosome reaction,
      but the relationship between cytoplasmic calcium (Ca2+in) levels in the two
      states was heretofore unknown. The Ca2+ indicator indo-1 was used to detect
      Ca2+in in moving hamster sperm in two sets of experiments. In the first
      experiment, activated, hyperactivated, and zona pellucida-induced acrosome
      reacted/hyperactivated sperm were analyzed at the time of peak of activity for
      each state. In the second experiment, sperm in all states were analyzed at one
      time point. In both sets, mean Ca2+in in the acrosomal region, postacrosomal
      region, and flagellar midpiece was greater in hyperactivated sperm than in
      activated sperm, and in acrosome-reacted/hyperactivated sperm than in
      unreacted/hyperactivated sperm (P < 0.001). Ca2+in had increased to a greater
      extent in the midpiece than in the head in hyperactivated sperm, while the
      reverse was true for acrosome-reacted sperm. Oscillations at the frequency of the
      flagellar beat cycle were detected chiefly in the proximal flagellar midpiece of
      acrosome-reacted sperm, as they had been previously reported to occur in
      activated and hyperactivated sperm. Thus, Ca2+in may be maintained at two
      different elevated levels in sperm, and continues to oscillate after the acrosome
      reaction.

PMID- 8579848
TI  - Differential incorporation of fatty acids into and peroxidative loss of fatty
      acids from phospholipids of human spermatozoa.
AB  - Intact human sperm incorporated radiolabelled fatty acids into membrane
      phospholipids when incubated in medium containing bovine serum albumin as a fatty
      acid carrier. The polyunsaturated fatty acids were preferentially incorporated
      into the plasmalogen fraction of phospholipid. Uptake was linear with time over 2
      hr; at this time sufficient label was available to determine the loss of fatty
      acids under conditions of spontaneous lipid peroxidation. Loss of the various
      phospholipid types, the loss of the various fatty acids from these phospholipids,
      and the overall loss of fatty acids were all first order. The loss of saturated
      fatty acids was slow with first order rate constant k1 = 0.003 hr-1; for the
      polyunsaturated fatty acids, arachidonic and docosahexaenoic acids, k1 = 0.145
      and 0.162 hr-1, respectively. The rate of loss of fatty acids from the various
      phospholipid types was dependent on the type, with loss from
      phosphatidylethanolamine being the most rapid. Among the phospholipid types,
      phosphatidylethanolamine was lost at the greatest rate. Analysis of fatty acid
      loss through oxidation products was determined for radiolabelled arachidonic
      acid. Under conditions of spontaneous lipid peroxidation at 37 degrees C under
      air in the absence of albumin, free arachidonic acid was found in the medium,
      along with minor amounts of hydroxylated derivative. All the hydroperoxy fatty
      acid remained in the cells. In the presence of albumin, all the hydroperoxy fatty
      acid was found in the supernatant bound to albumin; none could be detected in the
      cells. Albumin is known as a very potent inhibitor of lipid peroxidation in
      sperm; its action may be explained, based on these results, as binding the
      damaging hydroperoxy fatty acids. These results also indicate that a
      phospholipase A2 may act in peroxidative defense by excising a hydroperoxy acyl
      group from phospholipid and providing the hydroperoxy fatty acid product as
      substrate to glutathione peroxidase. This formulation targets hydroperoxy fatty
      acid as a key intermediate in peroxidative degradation.

PMID- 8579849
TI  - LL95 monoclonal antibody mimics functional effects of ZP3 on mouse sperm:
      evidence that the antigen recognized is not hexokinase.
AB  - In the mouse, a 95 kD sperm protein has been identified as a putative receptor
      for the zona pellucida glycoprotein ZP3. The 95 kD sperm protein is a tyrosine
      kinase substrate, with phosphorylation on tyrosine stimulated upon zona pellucida
      binding. The latter finding is observed not only in live cells but also in
      isolated sperm membranes and in an electroeluted 95 kD protein. Stimulation of 95
      kD protein tyrosine phosphorylation by zona pellucida is completely abolished by
      tyrosine kinase inhibitors, which effectively inhibit the sperm acrosome
      reaction. Since receptor oligomerization by ZP3 is essential for acrosome
      reaction triggering, we hypothesized that application of an external crosslinking
      agent will lead to the acrosome reaction, even in the absence of natural ligand
      ZP3. Here, we report the generation of a mouse monoclonal antibody (mAb) raised
      against the 95 kD protein. This antibody, termed LL95, mimics the bioactivities
      of ZP3 in inhibiting sperm-zona binding and inducing the acrosome reaction. The
      latter depends on receptor oligomerization. Immunolocalization revealed that the
      LL95 antigen is restricted to the head surface in the acrosomal region of live
      sperm. Thus, LL95 fulfills several criteria predicted for an antibody that
      recognizes a sperm receptor for the zona pellucida. Recently, it was reported
      that the amino acid sequence of the 95 kD protein we described corresponds to a
      mouse hepatoma hexokinase (Kalab et al., 1994: J Biol Chem 269:3810-3817).
      Although both hexokinase and LL95 antigen migrate at 95 kD in nonreducing gels,
      we show here that LL95 does not recognize hexokinase. Identification of different
      proteins is clear where hexokinase is a 116 kD protein and LL95 recognizes sperm
      proteins of 110 and 130 kD. Moreover, mAb anti-phosphotyrosine immunoprecipitates
      LL95 antigen under conditions where hexokinase is absent. Use of anti-hexokinase
      antibodies in gamete interaction assays failed to demonstrate any effect on
      either sperm-zona binding or acrosome reaction triggering. Finally,
      antihexokinase antibodies bind to a sperm tail antigen, thus direct involvement
      of hexokinase in gamete interaction seems improbable.

PMID- 8579850
TI  - Distribution of RNase MRP RNA during Xenopus laevis oogenesis.
AB  - RNase MRP is a ribonucleoprotein endoribonuclease found predominantly in
      nucleoli, but which has been associated with mitochondria and mitochondrial RNA
      processing. In order to analyze the intracellular localization of specific RNA
      components of ribonucleoproteins of this type, a whole-mount method for in situ
      hybridization in Xenopus laevis oocytes was employed. Results with specific
      probes (for both mitochondrial and nonmitochondrial RNAs) indicate that this
      procedure is generally effective for the detection of a variety of nucleic acids
      that reside in different cellular compartments. Probes used to detect the
      endogenous RNA component of RNase MRP (MRP RNA) during X. laevis oogenesis
      revealed a continuous nuclear signal as well as a possible dual localization of
      MRP RNA in nucleoli and mitochondria at developmental stages temporally
      consistent with both ribosomal and mitochondrial biogenesis. Genomic DNA encoding
      MRP RNA was injected into the nuclei of stage VI oocytes and correctly
      transcribed. The in vivo-transcribed RNA was properly assembled with at least
      some of its cognate proteins as demonstrated by immunoprecipitation with specific
      autoantiserum. In addition, detectable levels of the RNA were exported to the
      cytoplasm. This whole-mount procedure has permitted us to identify MRP RNA in
      situ at different developmental time points as well as during transcription of
      the injected gene, and suggests differential localization of MRP RNA during
      oogenesis consistent with its proposed function in both mitochondria and
      nucleoli.

PMID- 8579851
TI  - [Classification and pathogenesis of cerebral cortical malformations].
AB  - Cerebral cortical malformation is now diagnosed by neuroimagings, and important
      as a cause of developmental disorder or epilepsy. The classification of cortical
      malformations was tried from developmental aspect, and agyria in Miller-Dieker
      syndrome and polymicrogyria in Fukuyama-type congenital muscular dystrophy were
      compared on their pathogeneses. Unilateral hemimegalencephaly and focal cortical
      dysplasia were reviewed on literatures.

PMID- 8579852
TI  - [International training of child neurology].

PMID- 8579853
TI  - [Changes of neopterin in cerebrospinal fluid and serum in children with
      meningitis].
AB  - Neopterin is synthesized mainly by monocytes/macrophages and is considered to be
      a marker for activation of the cellular immune system. In patients with bacterial
      or aseptic meningitis, elevated neopterin levels in cerebrospinal fluid (CSF)
      have been demonstrated. We studied the time courses of CSF and serum neopterin in
      children with meningitis. The CSF neopterin levels on admission were
      significantly higher in patients with bacterial meningitis (82.4 +/- 37.0 nmol/L)
      than in those with aseptic meningitis (32.3 +/- 22.1 nmol/L) or in those with non
      pleocytotic CSF (6.9 +/- 4.4 nmol/L). The CSF neopterin levels in the patients
      with bacterial meningitis were remarkably increased (234.5 +/- 100.2 nmol/L) one
      day after admission, but the serum neopterin levels were not increased. There was
      no correlation between CSF neopterin levels and CSF cell count or CSF protein,
      nor between serum neopterin levels and serum C-reactive protein or peripheral
      leukocyte count. But the CSF neopterin levels one day after admission were
      related to the period of positive serum C-reactive protein. CSF neopterin levels
      in patients with bacterial meningitis were increased one day after admission. The
      levels in two patients with high levels of CSF IFN-gamma and TNF-alpha were
      remarkably increased. All patients with bacterial meningitis had received
      treatment with antibiotics and dexamethasone. It has been reported that TNF-alpha
      enhances the effect of IFN-gamma for neopterin release by macrophages in vitro
      and that dexamethasone has the same effect on IFN-gamma as TNF-alpha. The present
      study suggests that elevation of CSF neopterin in bacterial meningitis results
      from monocytes/macrophages costimulated with IFN-gamma, TNF-alpha and
      dexamethasone used in treatment.

PMID- 8579854
TI  - [Child neurology: present and future].

PMID- 8579855
TI  - [Comprehensive neuropsychological analysis of epileptic children with WISC-R,
      including profile analysis of subtests].
AB  - To evaluate intellectual functions of epileptic children, the Wechsler
      Intelligence Scale for Children-Revised (WISC-R) was performed on 69 children
      with epilepsy, and the test results were compared with their clinical symptoms
      and electroencephalographical findings. Both verbal IQ (VIQ) and performance IQ
      (PIQ) were significantly lower in the symptomatic group than in the idiopathic or
      cryptogenic groups, and also significantly lower in patients receiving
      polytherapy than monotherapy. PIQ was significantly low in patients treated with
      carbamazepine (CBZ), in those with poor control of seizures, in clumsy children,
      and cases with poor performance on visuo-motor tests. In the last two categories
      of patients there was an increased difference between VIQ and PIQ (discrepancy),
      and profile analysis revealed an impairment in non-verbal cognition and visual
      organization. On EEG records the patients with frontopolar (Fp) or frontal (F)
      focus had a significantly lower PIQ and an increased discrepancy. Migration of
      the epileptic focus during the periodic monitoring of EEG was also an important
      factor for an increased discrepancy. Furthermore, profile analysis suggested the
      impairment of the functions of the cerebral cortex associated with epileptic
      foci. These results indicate that either motor disability, such as clumsiness and
      minor motor disturbance, or epileptic focus on EEG are important factors
      affecting the assessment of neuropsychological aspects in epileptic children.

PMID- 8579856
TI  - [Hyperintense brain lesions on T1-weighted MRI after parenteral nutrition].
AB  - We experienced five children having T1-shortening lesions in basal ganglia or
      thalami on magnetic resonance imaging (MRI), which were supposed to be caused by
      manganese (Mn) overdoses. Instead of the presence of above mentioned lesions, no
      neurological manifestations corresponding to them had developed in all patients.
      This observation suggests that a MRI is useful for detecting the side effects
      caused by overdoses of Mn in patients having parenteral nutrition.

PMID- 8579857
TI  - [Oligohidrosis caused by zonisamide].
AB  - We studied 70 patients who took zonisamide (ZNS) in August 1994, to clarify the
      relation between ZNS and oligohidrosis. Twelve of the 70 patients were revealed
      to have oligohidrosis by the interview with patients' mothers. Six of these 12
      patients were evaluated by heat loading test, which showed a decreased sweat
      response in all patients. Five of the 12 oligohidrotic patients were evaluated by
      acetylcholine (Ach) loading test and all of them showed a decreased sweat
      response. On two patients poor sweat responses to heat loading and Ach loading
      recovered after discontinuation of ZNS. These results suggest that ZNS causes
      dysfunction of sweat glands.

PMID- 8579858
TI  - [Perinatal brain injury in infants with depressed EEG activities immediately
      after birth].
AB  - We investigated the developmental outcome and features of brain imaging in 33
      infants with moderate or severe depression of background EEG activities
      immediately after birth. Lesions due to perinatal injury were observed in 25
      infants on neonatal ultrasonography and/or childhood MRI. These findings strongly
      correlated with their gestational age. Periventricular leukomalacia and
      posthermorrhagic porencephaly were observed in preterm infants. On the other
      hand, perinatal injury of mature brain type, such as multicystic
      encephalomalacia, parasagittal infarct, bilateral basal ganglia/thalamic lesion,
      and subcortical leukomalacia, were observed in full-term infants. Periventricular
      leukomalacia rather correlated with moderate depression of EEG activities than
      severe depression like observed in full-term neonates who have brain lesions due
      to perinatal asphyxia.

PMID- 8579859
TI  - [Clinical and electroencephalographic studies in children with
      hemimegalencephaly].
AB  - Clinical and electroencephalographic (EEG) studies were performed in two children
      with hemimegalencephaly. The ages of seizure onset were 44 hours after birth in
      one infant and 33 days of postnatal life in the other patient. In both children,
      infantile spasms (IS) associated with hemihypsarrhythmia, developed at 1.5 months
      and 4 months, respectively. The subsequent clinical courses in these children
      were notable for frequent, intractable seizures. The seizures consisted of either
      generalized or partial seizures which originated from not only the hemimegalic
      hemisphere but also the contralateral one. Later, the clinical and EEG findings
      in one child indicated the development of Lennox-Gastaut syndrome (LGS). These
      findings suggested that the lesions of epileptogenesis in patients with
      hemimegalencephaly involved not only the pathological hemisphere, but also the
      contralateral hemisphere and subcortical structures. A detailed
      neurophysiological investigation in hemimegalencephaly could help the elucidation
      of the pathophysiology of intractable epilepsies, such as IS or LGS.

PMID- 8579862
TI  - [A case of Reye syndrome with hyperfibrinotic disseminated intravascular
      coagulation and central pontine and extrapontine myelinolysis--a hypothesis of
      pathogenetic mechanism in both complications].

PMID- 8579860
TI  - [Incidence patterns of cerebral palsy in Shiga, Japan, 1977-1986--an
      epidemiological study].
AB  - An epidemiological study of cerebral palsy (CP) in Shiga Prefecture, was
      performed by reviewing medical records of the Medical Center for Children in
      Shiga (MCCS) and related hospitals. The total number of CP patients identified at
      6 years old was 202 (117 boys and 85 girls) who were born during the ten years
      period between 1977-1986. The average prevalence of CP in Shiga Prefecture was
      calculated as 1.09 per 1,000 school children aged 6 years. The prevalence of CP
      was 9 fold among low birth weight infants (1,500-2,499 g) and 41 fold among very
      low birth weight infants (< 1,500 g), compared with that of mature infants (> or
      = 2,500 g). One hundred and thirty nine cases (69%) were term infants, and 63
      cases (31%) were preterm. Etiology of 139 term cases was considered to be
      prenatal in 50 cases (35%), perinatal in 37 cases (26%), postnatal in 3 cases
      (2%) and untraceable in 49 cases (35%), whereas prenatal in 12 cases (19%),
      perinatal in 7 cases (11%), and untraceable in 44 cases (70%) of 63 preterm
      cases. The prevalence rate of CP was fairly constant throughout the whole period
      of 1977-1986, but the term cases with perinatal etiologies significantly
      decreased in the period of 1982-1986, compared with those in the preceding period
      of 1977-1981. Children born weighting less than 1,500 g significantly increased
      in the later period. The improvement of perinatal care seems to play a major role
      on these changes. Sixty percent of term cases and 20% of preterm cases were
      considered to be due to prenatal factors which could not be prevented by the
      improvement of perinatal care.

PMID- 8579861
TI  - [A case of congenital brain tumor diagnosed during follow-up of neonatal
      intracranial hemorrhage].
AB  - We describe a three-year-old girl whose growing congenital brain tumor may have
      been responsible for her perinatal intracranial hemorrhage. The patient, born
      after an uneventful pregnancy and delivery, had an intracranial hemorrhage in the
      right frontal area, including the basal ganglia, as a newborn. Her only symptoms
      at that time were vomiting and fever. She improved both, clinically and
      neuroradiologically during the following weeks, and except for mild left
      hemiparesis, the patient developed with no other apparent neurological deficits.
      However, a follow-up brain CT scan at 3 years of age, disclosed a heterogeneous
      tumor with a 5 cm diameter in the same right frontal area as the neonatal
      hemorrhage. The tumor was surgically removed, and diagnosed as a benign mixed
      tumor composed of differentiated astrocytoma and meningioma elements. It is
      conceivable that the brain tumor may have been growing rather slowly since an
      early fetal stage. This case indicates the need of being aware that neonatal
      intracranial hemorrhages may be caused by bleeding of congenital brain tumors.

PMID- 8579863
TI  - [Treatment of H2-blocker-resistant reflux esophagitis in severely handicapped
      children with omeprazole].

PMID- 8579864
TI  - [Electron microscopic observation of wound healing process of the laryngeal
      mucosa in guinea pigs].
AB  - The ultrastructural changes of wound healing process following abrading of the
      laryngeal mucosa with a smooth file in 16 guinea pigs were observed by scanning
      and transmission electron microscopies. The results showed that: 1. the repair of
      the laryngeal mucosa epithelial defect was initiated from mobilization and
      migration of residual basal cells in the surrounding tissue onto the denuded
      epithelial surface; 2. the regenerated epithelium of migration covered small part
      of the denuded epithelial surface 24 hours after sustaining the injury; 3. five
      days later, all denuded epithelial surface was covered by the regenerated
      epithelium; 4. differentiation of the regenerated epithelium began 10 days after
      abrasion, and was completed 21 days after abrasion; 5. tonofilaments of
      distributed the minority, permeation, and concentration were seen in those cells
      of the regenerated epithelium respectively on the 1st, 5th and 10th days after
      abrasion. Particularness of differentiation of the regenerated epithelium was
      discussed.

PMID- 8579865
TI  - [Uvulopalatopharyngoplasty: safety managements and causes of failure].
AB  - Uvulopalatopharyngoplasty operations on 250 patients were reported. The safety
      managements and failing causes of UPPP were discussed. Safety managements
      included 5 aspects: 1. using-local anesthesia rather than general anesthesia; 2.
      intraoperative monitor ECG, blood pressure and oxygen saturation; 3. tracheotomy
      should be performed in the severe cases before UPPP; 4. preoperative physician
      consultation if patients complicated with cardiopulmonary problems; 5. separated
      nasal and UPPP operations into two stages. Failing causes included 4 aspects: 1.
      improper indication; 2. polyplace obstruction, specially hypopharyngeal
      obstruction; 3. postoperative local hemorrhage and infection; 4. the experience
      and the skill of the surgeon.

PMID- 8579866
TI  - [Indications of tracheotomy before uvulopalatopharyngoplasty in patients with
      severe obstructive sleep apnea syndrome].
AB  - 9 cases with tracheotomy before uvulopalatopharyngoplasty (UPPP) were analysed.
      all of them suffered from severe obstructive sleep apnea syndrome (OSAS). The
      indications of tracheotomy included, (1) the nocturnal lowest oxygen saturation
      was lower than 50%; (2) apnea hyponea index (AHI) higher than 50; (3) significant
      cardiopulmonary problems; (4) severe hypoxia symptoms; (5) obesity, brachyneck
      and glossohypertrophia.

PMID- 8579867
TI  - [Surgical treatment of the bilateral abductor paralysis].
AB  - 27 patients with bilateral vocal cord paralysis were treated in the First
      Clinical Medical College of Beijing Medical University, and all of them were
      followed up at least one year after treatment. According to the length of the
      vocal cord and the degree of the anterior angle of the thyroid cartilage, one of
      the three different surgical procedures would be selected to alleviate the
      symptoms of bilateral abductor paralysis. The width of glottic chink after
      treatment is the paramount index. The average estimated size of the posterior
      glottic chink or point of maximum width of glottic chink should be equal to or
      bigger than 4mm after surgical treatment. The open approach to arytenoidectomy
      Woodman's Technique was performed in 15 patients, and among them the tracheal
      cannulas were removed in 11 cases, and 8 cases had a glottic chink bigger than
      4mm width. In 9 cases with short length vocal cord and narrow anterior angle of
      the thyroid cartilage, a modified hemilaryngectomy was used by thyrotomical
      approach, and a successful result was obtained with good to excellent exercise
      tolerance for social activity. Unfortunately, in the remaining 3 patients, the
      nerve-muscle pedicle technique reinnervation of bilateral vocal cord paralysis
      was applied, and no patient demonstrated visible inspiratory vocal cord
      abduction. Although this type of operation might totally reconstruct respiratory
      function without phonation impairment, the clinical result was not certain.

PMID- 8579868
TI  - [Laryngeal paralysis and laryngospasm].
AB  - The intrinsic laryngeal muscle potential was recorded with electromyography.
      Vocal cord movements were observed by a video stroboscope. Laryngeal paralysis is
      divided into mild, moderate, and severe degrees based on the potentials of
      intrinsic laryngeal muscles and on the status of vocal cord movements. In the
      past 11 years (from 1983 to 1993) 1211 cases were diagnosed as having mild,
      moderate, and severe laryngeal paralysis. Among them, there were 11 cases with
      laryngospasm including 3 mild, 2 moderate, and 6 severe cases. The findings
      obtained from careful observation on these 11 cases of laryngospasm demonstrated
      that there were certain relationships between laryngeal paralysis and
      laryngospasm. During the course of exacerbation or restoration of paralysis, the
      laryngospasm may occur.

PMID- 8579869
TI  - [Effect of focal cochlear vascular lesion on endocochlear potential in guinea
      pigs].
AB  - The alterations in endocochlear potential(EP) in response to the total cochlear
      ischemia induced by varied experimental manipulations have been studied. However,
      whether damage to the focal microvessel in the lateral wall of the cochlea can
      affect the EP value is still unknown. In current investigations, we adapted a
      photochemical method to produce focal microvessel injury in the lateral wall of
      the guinea pig cochlea and examine effects of these insults on EP in the same
      region. It was found that the small focal microvessel lesion (approximately 0.2mm
      x 0.3mm) did not induce significant changes in EP value. Furthermore, the
      relative large microvessel lesion (approximately 0.2mm x 0.3mm) did not induce
      significant changes in EP value. Furthermore, the relative large microvessel
      lesion (approximately 0.2mm x 0.8mm) produced only a slight decrease in the EP
      value with experimental procedures and these changes were not significantly
      different as compared with those in the control group subjects. The results from
      this study suggest that after focal microvessels in the lateral wall of the
      cochlea are injured, some compensation mechanisms may play a role in maintaining
      the cochlear function.

PMID- 8579870
TI  - [Ultracytochemical localization on Na(+)-K(+)-ATPase activity in the guinea pig
      endolymphatic sac].
AB  - It is well-known that Na(+)-K(+)-ATPase plays an important role in active
      transportion of sodium (Na) and potassium (K) ions across the epithelium. This
      paper reports the ultrastructural localization of the K(+)-NPPase reflecting
      Na(+)-K(+)-ATPase activity in the guinea pig endolymphatic sac (ES) with the lead
      citrate one step method. The ultrathin sections viewed in the transmission
      electron microscope revealed that the reaction product was restricted to the
      cytoplasmatic side of the basolaterl plasma membranes of the ES epithelial cells.
      And the reactivity could be traced all the way up to the level of tight junctions
      close to the luminal aspect of the cells. On the other hand, the luminal plasma
      membrane of the epithelial cells showed no enzyme activity. Our findings suggest
      that the rich Na(+)-K(+)-ATPase enzyme activity is preferentially localized on
      the basolateral plasma of membrane of the ES epithelial cells. Possible
      physiological mechanism of Na(+)-K(+)-ATPase in the Na(+)-K+ ion transport of ES
      epithelial cells is discussed.

PMID- 8579871
TI  - [Simultaneous staining with fluorescein diacetate-propidium iodide to determine
      isolated cochlear outer hair cell viability of guinea pig].
AB  - A simultaneous double-staining procedure using fluorescein diacetate (FDA) and
      propidium iodide (PI) is discribed for use in the determination of isolated
      cochlear outer hair cell viability. With exciter light, viable cells fluoresce
      bright green, while nonviable cells are bright red. In cell culture and
      cytotoxicity studies, double-staining with FDA-PI is a accurate method to
      discriminate between live and nonviable cells.

PMID- 8579872
TI  - [Laboratory diagnosis of autoimmune sensorineural hearing loss with modified
      western blotting method].
AB  - Anti-membranous labyrinth proteins antibody were tested in suspectable autoimmune
      sensorineural hearing loss (ASNHL) with a modified western blotting method. 5
      strongly positive bands (including 68,000) existed in at most 18 of 25 cases
      (72%). This method was found to be more sensitive than the routine one (40%).
      Anti-membranous proteins of Klebsiella pneumoniae antibodies were also found in 7
      of 9 tested patients.

PMID- 8579873
TI  - [Clinical analysis of 102 patients with congenital inner ear malformation].
AB  - Hearing loss and CT findings of 200 ears from 102 cases with congenital
      malformation of inner ear were included in our study. Hearing loss was typically
      bilateral severe, or total deafness. 75 percent of them were found deaf within
      one-year-old. In addition, 47 patients' (46%) mothers were noted to have caught a
      cold in first trimester of pregnancy. Temporal bone abnormalties were described
      as five types: 1. Michel malformation, 2. Mondini malformation, 3. enlargement of
      the vestibular aqueducts, 4. developmental deformity of cochlear aqueduct, 5.
      developmental deformity of internal acoustic meatus. Most cases showed
      malformations of vestibule or vestibular aqueducts.

PMID- 8579874
TI  - [Histopathologic observation and 3DCT reconstruction of the nasal cavity and
      paranasal sinuses in children with cleft palates].
AB  - The morphologic characteristics of nasal cavity and paranasal sinuses in children
      with cleft palate were studied by means of histopathology, CT scan, computer
      aided image analysis and three-dimensional CT (3DCT) reconstruction. Our results
      suggested (1) incompetent velopharynx is the main reason for high incidence of
      sinusitis in children with cleft palate; (2) computer-aided image analysis,
      together with 3DCT reconstruction, may calculate and demonstrate the volume and
      shape of the paranasal sinuses. We believe this method may be useful in the
      future to study the development of the paranasal sinuses in children. 3DCT
      reconstruction provides a better understanding of the size and invasion of the
      lesion located in nasal cavity and paranasal sinuses. This method may be used as
      an aid to teaching and surgical planning.

PMID- 8579875
TI  - [Clinical observation and therapeutic mechanism of blocking agent of substance P
      nerves in the treatment of perennial allergic rhinitis].
AB  - This paper reported the clinical effects and therapeutic mechanism of blocking
      agent of substance P(SP) nerves on prerennial allergic rhinitis. We applied
      capsaicin (CAP) in the treatment of 50 cases of perennial allergic rhinitis once
      a week and 4 times as a therapeutic course. By using highly specific and highly
      sensitive SP radioimmunoassay, the SP contents in nasal secretions were
      determined before and after CAP therapy. The results showed that clinical
      symptoms of allergic rhinitis were obviously relieved and SP content in the nasal
      secretions was remarkably reduced from 29.444 +/- 14.280pmol/L before CAP therapy
      to 16.848 +/- 10.622 pmol/L after therapy (P < 0.001). Of the 50 cases, 35 cases
      (70.0%) showed the best effects, 12 cases (24.0%) better effects and 3 cases
      (6.0%) no effects. The total effective rate was 94.0%. The study indicated that
      therapeutic mechanism of CAP on perennial allergic rhinitis is related to the
      reducing of SP and the blocking of axonal reflex of the SP nerves.

PMID- 8579876
TI  - [Use of A-mode ultrasound in the diagnosis of maxillary sinus diseases].
AB  - This paper reported our recent attempt to utilize the nasal ultrasonography (ECHO
      TE-11) in the diagnosis of maxillary sinus diseases. We performed nasal
      ultrasonography on 160 individuals (69 with normal maxillary sinus; 91 with
      chronic maxillary sinus diseases). In the normal maxillary sinus group, the
      proportion of diagnostic accuracy was 89.9% (62/69) and in the maxillary
      sinusitis group, the proportion was 91.9% (80/87). 4 cases, including
      postoperative maxillary cyst, benign tumor and malignant tumor of the maxillary
      sinus, could be accurately diagnosed by this technique. The precautions were also
      discussed.

PMID- 8579877
TI  - [Aspergilus nasal sinusitis endoscopic surgery].
AB  - Five cases of non-invasive fungal sinusitis were reported. Among them were 2
      cases of maxillary, 2 of maxillo-ethmoid and sphenoid sinus. All the patients
      were operated under endoscopic intranasal approach. The pathological diagnosis of
      all 5 cases was aspergills infection. The pathogenesis were conditional such as
      unclean working situation, deviation of nasal septum, polyposis and infection.
      The disease was easily confused with common infectious disease. The pathogenic
      factor, diagnosis and treatment were discussed.

PMID- 8579878
TI  - [Adjuvant chemotherapy in advanced squamous cell carcinoma of the head and neck].
AB  - A prospective randomized study in a total of 36 patients with previously
      untreated advanced squamous cell carcinomas of the head and neck was performed.
      20 patients were in group of 120-hour continuous infusion 5-Fu and bolus
      cisplatin (continuous group). Over-all response rates of continuous group were
      90% (complete response 20%, partial response 70%) and of conventional group were
      43.8% (6.3%, 37.5%). The differences in the over-all response rates of two groups
      were statistically significant at P = 0.0039. There was no difference between the
      two chemotherapy toxicity (P > 0.05), and the toxicity was clinically acceptable.
      The authors concluded that two or three course of 120-hour 5-Fu continuous
      infusion and bolus cisplatin is highly effective and safe adjuvant treatment in
      patients with advanced carcinoma of the head and neck.

PMID- 8579879
TI  - Cell proliferation in lung fibrosis-associated hyperplastic lesions.
AB  - 1. Cell proliferative activity of atypical bronchioalveolar epithelia in lung
      fibrosis cases treated with bleomycin (BLM) or radiation was investigated by
      studying the histochemistry of the argyrophil nucleolar organiser regions
      (AgNORs) and proliferating cell nuclear antigen (PCNA). 2. Five and 14 autopsy
      cases of individuals who died of pulmonary fibrosis, caused by BLM treatment and
      irradiation respectively, were compared with (i) six control subjects who proved
      to have no apparent fibrosis of the lung at autopsy and (ii) four lung squamous
      cell carcinoma cases. 3. Histopathologically, both the BLM-treated and irradiated
      cases showed extensive collapse of the lung caused by severe fibrosis, although
      proliferative epithelial lesions such as atypical bronchioloalveolar hyperplasia
      and squamous metaplasia were more prominent in the former. 4. The mean AgNOR
      numbers in both atypical hyperplasias and metaplasias, of either BLM or
      irradiation cases, were significantly higher than in control bronchioalveolar
      epithelial areas, whereas they were lower than in the lung cancers. Data for PCNA
      labelling indices were in time with those for AgNORs. 5. The results indicate
      that atypical hyperplastic lesions in the bronchioloalveoli arising during the
      fibrosing process as induced by BLM, and by irradiation, are highly
      proliferative.

PMID- 8579880
TI  - HFA-134a (1,1,1,2-tetrafluoroethane); lack of oncogenicity in rodents after
      inhalation.
AB  - 1. Groups of 60 male and 60 female B6C3F1 mice or HanIbm Wistar rats were exposed
      to HFA-134a using snout-only inhalation exposure techniques for periods of one
      hour daily for at least 104 weeks. HFA-134a was delivered directly from cylinders
      at vapour concentrations of 2500, 15,000 and 75,000ppm for mice and from metered
      dose inhalers at vapour concentrations of 2500, 10,000 and 50,000ppm for rats. 2.
      Intended dosages were achieved. 3. Evidence of absorption was found at each dose
      level and was dose related. 4. Neither species suffered treatment related effects
      on survival, clinical signs, body weights, haematology nor on the type,
      incidence, site or severity of gross lesions. 5. There was no effect of treatment
      on the type, incidence, site or severity of neoplasms in mice or rats. 6. There
      were no non-neoplastic findings related to treatment in mice. 7. HFA-134a was
      considered not to be oncogenic and to provide a safe alternative to
      chlorofluorocarbons for use in pharmaceutical metered-dose inhalers.

PMID- 8579881
TI  - An overview of the toxicology of HFA-134a (1,1,1,2-tetrafluoroethane).
AB  - 1. This paper reviews the results of preclinical toxicology studies on HFA-134a
      carried out by Glaxo Research and Development Ltd. 2. A comprehensive range of
      studies was conducted in animal models suitable for the type of investigation. 3.
      The inhalation route of administration was used in all in vivo studies (with the
      exception of local tolerance and sensitisation studies) as patients will be
      exposed only to vapour during actuation of metered-dose inhalers. Cell cultures
      used for in vitro studies were also exposed to the vapour. 4. There was no
      mortality of rodents or dogs at extremely high vapour concentrations (81%v/v) 5.
      HFA-134a was considered not to be toxic or oncogenic and to provide a safe
      alternative to chlorofluorocarbons for use in pharmaceutical metered-dose
      inhalers.

PMID- 8579883
TI  - Neurotoxicity following the ingestion of a Chinese medicinal plant, Alocasia
      macrorrhiza.
AB  - 1. A case of poisoning due to the raw root tuber of a Chinese medicinal plant,
      Alocasia macrorrhiza is presented. 2. The patient developed neurological (severe
      pain and numbness in the perioral area and throat) and gastrointestinal (nausea,
      vomiting, abdominal pain) symptoms immediately after eating the root tuber. 3. A
      macrorrhiza has properties and morphology very similar to another medical plant.
      A. odora. The root tuber of the latter is known to contain a neurotoxin
      sapotoxin.

PMID- 8579882
TI  - Life-time exposure to dichlorvos affects behaviour of mature rats.
AB  - Wistar rats were exposed to dichlorvos [CAS number 62737]. Doses were 1/25; 1/50;
      and 1/100 LD50, that is 3.88; 1.94; 1.46; and 0.97 mg kg-1 DDVP, respectively,
      throughout gestation (GD1-birth) and during suckling via oral dosing to the dams,
      and then via the same doses by gavage for the rest of their lives. The offspring
      were tested in an open field (OF), a multiple T-maze, and in a 'novelty-induced
      grooming' test to assess behavioural competence as adults. Dose-related increases
      in running time and incorrect choices in the maze were observed during the first
      2 weeks of a 3-week study at 9-11 weeks of age. Horizontal activity was
      increased, vertical activity decreased, and defecation decreased in the OF at 9
      12 weeks of age; these changes were again dose-related. Sleep was also affected
      at 12 weeks of age. AChE activity in the brain and in blood at sacrifice was
      roughly 40% to 65% of control, again reflecting the doses administered. The
      significantly changed behavioural profile of DDVP treated rats may serve as a
      useful biomarker to judge functional damage of CNS properties.

PMID- 8579884
TI  - Skin irritation testing in man for hazard assessment--evaluation of four patch
      systems.
AB  - 1. The limitations of the Draize rabbit skin irritation test for hazard
      evaluation for man are widely documented. Nevertheless it remains the prescribed
      method for determining acute skin irritations hazard. 2. While the use of human
      testing for risk assessment of irritants is well established, the use of
      predictive testing in man for hazard identification has not been explored widely,
      and this is the object of the research programme. 3. The experiment described in
      this report evaluates the sensitivity of four patch testing systems (Finn
      chamber, Hill Top patch, Van der Bend chamber, and Webril patch) using a total of
      six irritant substances. 4. Following preliminary range-finding experiments, test
      materials were applied to the upper outer arm for up to 4 h. Assessments were
      performed immediately after patch removal and at 1, 24, 48, and 72 h. 5. Webril
      and Hill Top patches generated the greatest levels of response, although
      responses with Finn and Van der Bend were observed. Hill Top patches are
      recommended for future development work. 6. The use of very small preliminary
      panels to predict the effects in larger panels using different volunteers was
      only of limited value as each volunteer was found to have different irritant
      thresholds.

PMID- 8579885
TI  - Chemical respiratory allergy. Toxicological and occupational health issues.

PMID- 8579886
TI  - Exploring the roots of the biliary tree.

PMID- 8579887
TI  - Superoxide meets the challenge.

PMID- 8579888
TI  - Strategy for nuclear proliferation.

PMID- 8579889
TI  - Proceedings of the XII International Conference on Calcium Regulating Hormones.
      Melbourne, Australia, February 14-19, 1995.

PMID- 8579890
TI  - Bone and cancer: pathophysiology and treatment of metastases.
AB  - The variability of different primary tumors in the susceptibility to metastatic
      bone disease is poorly understood. Factors that determine the viability of
      metastatic cells are also poorly understood, but may depend in part upon gene
      expression of PTHrP and the vitamin D receptor. In contrast, much more is known
      of the manner in which metastatic disease affects bone remodeling to induce
      osteolytic bone disease. Mechanisms include a generalized increase in activation
      frequency at sites close to metastatic tissue, an imbalance between the amount of
      bone formed and that resorbed within resorption cavities, and uncoupling of bone
      formation from bone resorption. The greatest morbidity from metastatic bone
      disease arises from osteolytic disease and gives rise to hypercalcemia, bone
      pain, and fractures. Because osteolysis is primarily mediated by the activation
      of osteoclasts, there has been a great deal of interest in the use of agents
      which primarily affect bone metabolism to alter the natural history of metastatic
      bone disease. Nonsteroidal antiinflammatory agents and cytotoxic agents are
      capable of inducing responses in bone, but are limited by their toxicity when
      effective doses are utilized. The use of calcitonin in the long-term suppression
      of osteolysis has also been disappointing. The bisphosphonates are, however,
      capable of inducing sustained decreases in osteoclast activity and numbers in
      patients with osteolytic bone disease. There are now several studies which have
      examined the effects of the bisphosphonates on skeletal morbidity in breast
      cancer. Both clodronate and pamidronate decrease the incidence of hypercalcemia,
      bone pain, and pathological fractures, but do not significantly alter
      mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579892
TI  - Putting the bits and pieces of the RET proto-oncogene puzzle together.
AB  - The RET proto-oncogene has been implicated in the causation of papillary thyroid
      carcinoma, multiple endocrine neoplasia types 2A (MEN 2A) and 2B (MEN 2B), and
      Hirschsprung's disease. The mutations in these syndromes can be categorized into
      activating or inactivating mutations. Activating mutations of a cysteine-rich
      extracellular region cause enhanced dimerization of the RET tyrosine kinase
      receptor and autophosphorylation, and are causative for MEN 2A and familial
      medullary thyroid carcinoma (FMTC). An activating mutation of the tyrosine kinase
      domain causes increased autophosphorylation but does not affect the state of
      dimerization. A variety of inactivating mutations of the RET proto-oncogene,
      which result in defective protein formation, are causative for Hirschsprung's
      disease.

PMID- 8579891
TI  - Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications.
AB  - Vitamin D is absolutely essential for the maintenance of a healthy skeleton.
      Without vitamin D, children develop rickets and adults exacerbate their
      osteoporosis and develop osteomalacia. Casual exposure to sunlight is the major
      source of vitamin D for most people. During exposure to sunlight, ultraviolet B
      photons photolyze cutaneous stores of 7-dehydrocholesterol to previtamin D3.
      Previtamin D3 undergoes a thermal isomerization to form vitamin D3. Increased
      skin pigmentation, changes in latitude, time of day, sunscreen use, and aging can
      have a marked influence on the cutaneous production of vitamin D3. Once vitamin
      D3 is formed in the skin or ingested in the diet, it must be hydroxylated in the
      liver and kidney to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is now recognized
      that a wide variety of tissues and cells, both related to calcium metabolism and
      unrelated to calcium metabolism, are target sites for 1,25(OH)2D3. 1,25(OH)2D3
      stimulates intestinal calcium absorption and mobilizes stem cells to mobilize
      calcium stores from bone. Noncalcemic tissues that possess receptors for
      1,25(OH)2D3 respond to the hormone in a variety of ways. Of great interest is
      that 1,25(OH)2D3 is a potent antiproliferative and prodifferentiation mediator.
      As a result, 1,25(OH)2D3 and its analogs have wide clinical application in such
      diverse clinical disorders as rheumatoid and psoriatic arthritis; diabetes
      mellitus type I; hypertension; cardiac arrhythmias; seizure disorders; cancers of
      the breast, prostate, and colon; some leukemias and myeloproliferative disorders;
      chemotherapy-induced hair loss; and skin rejuvenation as well as skin diseases
      like psoriasis and ichthyosis.

PMID- 8579893
TI  - Pathogenesis of osteoporosis.
AB  - Fractures, the clinical outcome associated with osteoporosis, have a complex
      pathogenesis involving, in most cases, both trauma to the bone and increased
      skeletal fragility. Recent evidence also suggests that the geometry of the bone
      is important in determining fracture risk, and geometric properties are in part
      genetically determined. Skeletal fragility is largely determined by bone mass and
      the microstructure of bone. Loss of trabeculae and their connections has been
      well documented and undoubtedly contributes to risk of some fractures.
      Microdamage has also been shown to occur within the skeleton and could contribute
      to fragility. Peak bone mass is a major factor in determination of subsequent
      fracture risk and it has both genetic and environmental determinants. Twin
      studies have suggested a major genetic contribution and that a few genes may be
      responsible, but these genes have not been clearly identified. Nutrition,
      especially calcium intake, and exercise also contribute to the determination of
      peak bone mass and are especially important during the major period of bone
      acquisition up to the age of 18. Bone loss among women begins in the
      perimenopausal period, although loss from the hip begins earlier. The loss is
      associated with both estrogen and androgen concentrations. Later in life other
      factors such as the development of secondary hyperparathyroidism may contribute
      to the continued loss of bone. Males lose bone at about half the rate of females,
      but the underlying contributing factors are not well documented. The pathogenesis
      of osteoporotic fractures is complex, but this allows for the development of
      multiple interventions, which may reduce the frequency of such fractures.

PMID- 8579894
TI  - Present and future of osteoporosis therapy.
AB  - In the 50-year "modern" history of osteoporosis, there have been about 17
      antifracture studies with sufficient attention to design to allow inference
      regarding efficacy. Antivertebral fracture efficacy has been reported with
      etidronate, estrogen patch, calcitonin, and 1,25-dihydroxyvitamin D. Two studies
      using fluoride were positive, and two were negative. Hip fractures have been
      neglected. One study showed efficacy of hip protectors, one showed efficacy of
      vitamin D and calcium in nursing home dwellers. The source of most hip fractures
      is the community. One community based antihip fracture efficacy study using
      annual injections of vitamin D was positive. There have been no antivertebral or
      antihip fracture studies in men, or in corticosteroid-related osteoporosis in men
      or women. Lack of independently repeated demonstration of efficacy, small
      fracture numbers, and data pooling in some of these (the best) studies leave
      great uncertainty. Estrogen and bisphosphonates appear to be the best options at
      this time. New data suggest that calcium supplementation is likely to reduce the
      rate of bone loss and perhaps reduce fracture rates. The challenge is to maintain
      and restore the constituents of bone mineral density (BMD), that is: to promote
      periosteal and endosteal bone formation; reduce endosteal bone resorption and
      cortical porosity; and increase trabecular thickness, number, and connectivity.
      There are many opportunities, for instance, intermittent parathyroid hormone
      (PTH) increases bone strength and, with estrogen, may increase connectivity. The
      anabolic effects of PTH may be partly mediated by IGF-1. IGF-1 increases
      periosteal, endosteal, and trabecular bone formation, cortical and trabecular
      width, and trabecular and endocortical connectivity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8579896
TI  - Functional properties of the PTH/PTHrP receptor.
AB  - The PTH/PTHrP receptor belongs to a novel family of G-protein-coupled receptors
      which also includes an insect receptor for a diuretic hormone and the protein
      encoded by a genomic DNA clone from Caenorhabditis elegans. Despite significant
      structural conservation, rat, opossum, and human PTH/PTHrP receptor homologs
      display distinct functional characteristics when tested with either [Arg2,
      Tyr34]hPTH(1-34)amide or [Nle8.18, Tyr34]bPTH(7-34)-amide. These PTH analogs, and
      chimeras between rat/opossum and between rat/human PTH/PTHrP receptors, led to
      the identification of receptor residues that appear to be involved in
      ligand/receptor interaction and receptor activation, respectively. The search for
      mutations in the PTH/PTHrP receptor gene in genomic DNA of patients with
      pseudohypoparathyroidism type Ib (PHP-Ib) revealed several silent polymorphisms
      and a missense mutation in the receptor's tail region which did not affect
      receptor function. Mutations in the PTH/PTHrP receptor are therefore rarely, if
      at all, responsible for PHP-Ib. A mutation in the PTH/PTHrP receptor is, however,
      the most likely cause of Jansen-type metaphyseal chondrodysplasia, a rare form of
      short-limbed dwarfism which is associated with severe hypercalcemia despite
      normal or low levels of circulating PTH and PTHrP. A missense mutation was
      identified which causes constitutive, ligand-independent receptor activation, and
      thus explains the laboratory and the growth-plate abnormalities in affected
      individuals.

PMID- 8579895
TI  - New understanding of the molecular mechanism of receptor-mediated genomic actions
      of the vitamin D hormone.
AB  - The nuclear vitamin D receptor (VDR) binds the 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3]hormone with high affinity and elicits its actions to regulate gene
      expression in target cells by binding to vitamin D-responsive elements (VDREs).
      VDREs in positively controlled genes such as osteocalcin, osteopontin, beta 3
      integrin, and vitamin D-24-OHase are direct hexanucleotide repeats with a spacer
      of three nucleotides. The VDR associates with these VDREs with the greatest
      affinity as a heterodimer with one of the family of retinoid X receptors (RXRs).
      VDR consists of an N-terminal zinc finger domain that determines DNA binding, a
      "hinge" segment and a C-terminal hormone binding domain which also contains two
      conserved regions that engage in heterodimerization with an RXR on the VDRE. The
      role of the 1,25(OH)2D3 ligand in transcriptional activation by the VDR-RXR
      heterodimer is to alter the conformation of the hormone-binding domain of VDR to
      facilitate strong dimerization with RXR, which results in ligand-enhanced
      association with the VDRE. Thus RXR is recruited into a heterocomplex by liganded
      VDR. The natural ligand for the RXR coreceptor, 9-cis retinoic acid, suppresses
      both VDR-RXR binding to the VDRE and 1,25(OH)2D3-stimulated transcription,
      indicating that 9-cis retinoic acid diverts RXR away from being the silent
      partner of VDR to instead form RXR homodimers. Recent data reveal that after
      binding RXR, a subsequent target for VDR in the vitamin D signal transduction
      cascade is basal transcription factor IIB (TFIIB).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8579897
TI  - Mutations in collagen genes resulting in metaphyseal and epiphyseal dysplasias.
AB  - Genetic mapping and positional cloning of genes, in which mutations lead to
      osteochondrodysplasias in humans and mice, combined with studies of transgenic
      mice with mutations in cloned genes, is providing novel and exciting insights
      into the molecular mechanisms of cartilage and bone development and growth as
      well as the basis for a variety of osteochondrodysplasias. Studies of mice with
      targeted disruption of c-src and c-fos have shown that these two genes have
      essential roles in the function and differentiation of osteoclasts. Combined
      mouse and human studies demonstrate that a unique extracellular matrix molecule
      (collagen X) in the mineralizing hypertrophic zone of growth plates is essential
      for normal growth plate function. Mutations in this molecule cause metaphyseal
      chondrodysplasia type Schmid (MCDS) in humans. Identification of the gene causing
      autosomal recessive chondrodysplasia in mice demonstrates that the quantitatively
      minor fibrillar collagen XI is essential for the cohesive properties of cartilage
      and the normal differentiation and spatial organization of chondrocytes in growth
      plates. Finally, mutations in all three collagen components of cartilage fibrils,
      collagens II, IX, and XI, have been found to cause a spectrum of clinical
      disorders, ranging from severe, perinatal lethal, osteochondrodysplasias to
      extremely mild conditions presenting themselves as a genetic predisposition to
      osteoarthritis.

PMID- 8579898
TI  - Interactions of connective tissue cells with the extracellular matrix.
AB  - Interactions between cells and extracellular matrix components have been shown to
      be crucial for the regulation of tissue differentiation and function in a range
      of organisms. Recent work has defined several families of receptors by their
      domain structure, and the peptide sequence motifs in the ligands which they
      recognize have been elucidated. Thus, the integrin fibronectin receptor has been
      shown to recognize "RGD" and other sequences within matrix and plasma proteins.
      Disruption of these integrin-ligand interactions by gene inactivation via
      homologous recombination of receptor or ligand, and by use of RGD inhibitors or
      antibodies, modifies embryonic development and cellular function. Recent evidence
      from several receptor systems has also demonstrated that they can partake in
      signal transduction, in addition to adhesive events, leading to the definition of
      further functional activities. The range of receptors and their ligands involved
      in matrix interactions and data on their role in a variety of cellular systems
      are summarized. The therapeutic implications of a fundamental approach to
      cellular adhesion processes will be highlighted by considering the role of the
      alpha v beta 3 integrin receptor in osteoclastic bone resorption.

PMID- 8579899
TI  - Osteoclast function in Paget's disease and multiple myeloma.
AB  - Paget's disease of bone and multiple myeloma are characterized by increased
      numbers of osteoclasts and markedly increased bone resorption at the sites of the
      disease. In Paget's disease the osteoclasts are abnormal morphologically and
      contain viral-like nuclear inclusions, but in multiple myeloma the osteoclasts
      are normal. The bone lesions in both Paget's disease and multiple myeloma appear
      to be due to local stimulation of osteoclast formation and bone resorption. In
      situ hybridization techniques, bone marrow cultures, and cytokine assays have
      been used to examine osteoclast function in Paget's disease and multiple myeloma.
      Interleukin-6 (IL-6) has been implicated as a potential mediator for the
      increased osteoclast activity in both diseases. In Paget's disease, IL-6 is
      produced by the osteoclasts, the osteoclasts express IL-6 receptors and IL-6
      mRNA, and increased levels of IL-6 are present in the marrow plasma and serum of
      these patients. Similarly, increased levels of IL-6 have been detected in sera
      from some patients with multiple myeloma. Multiple myeloma cells do not produce
      IL-6 in vivo but marrow stromal cells or the osteoclasts may be the source of IL
      6 in multiple myeloma. IL-6 is a growth factor for multiple myeloma cells, and
      treating patients with anti-IL-6 decreases the tumor burden in some patients.
      Thus, IL-6 may be an autocrine/paracrine factor in both Paget's disease and in
      multiple myeloma. Multiple myeloma cells also produce osteoclast activating
      factors (OAFs) that can stimulate osteoclast formation and activity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8579900
TI  - Role of cytokines in bone resorption.
AB  - It has been established during the past few years that interleukin(s)-1, -6, -11
      (IL-1, IL-6, IL-11), and tumor necrosis factor (TNF) can stimulate osteoclast
      development and thereby the process of bone resorption. Moreover, upregulation of
      the production and/or action of IL-6 has been implicated in the pathogenesis of
      disease states characterized by excessive osteoclastic bone resorption, including
      the osteopenias associated with loss of either ovarian or testicular function.
      This article highlights this evidence and attempts to clarify the role of
      cytokines in the bone loss associated with gonadal deficiency. Specifically, it
      reviews data demonstrating that the protective effects of estrogens and androgens
      on the skeleton are mediated through their ability to inhibit IL-6 production.
      Both of these steroids exert their effects by inhibiting the transcriptional
      activity of the IL-6 gene promoter via mechanisms involving their respective
      specific receptors. Upon loss of gonadal function in either sex, there occurs an
      upregulation of osteoclast formation which is mediated by IL-6. Consistent with
      this, IL-6-deficient mice do not exhibit an increase in the formation of
      osteoclasts after ovariectomy or orchidectomy, and are protected from the bone
      loss caused by the loss of gonadal function in either sex. Even though these
      observations establish that IL-6 is an essential pathogenetic factor in the bone
      loss caused by gonadal deficiency, it remains unclear whether IL-6 is the sole
      pathogenetic factor or whether IL-1, TNF, and IL-11 may also be involved.
      However, in contrast to IL-6, these cytokines do not seem to be directly
      regulated by sex steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579901
TI  - Cloning and functional characterization of extracellular Ca(2+)-sensing receptors
      from parathyroid and kidney.
AB  - Parathyroid cells recognize and respond to (i.e., "sense") minute perturbations
      in the extracellular ionized calcium concentration (Ca2+o), but the mechanisms
      underlying this process have remained obscure. Recently, we employed expression
      cloning in Xenopus laevis oocytes to isolate a cDNA coding for a Ca2+o-sensing
      receptor from bovine parathyroid. Like the native receptor, the cloned Ca2+o
      sensing receptor stimulates phospholipase C (PLC) in a G-protein-dependent manner
      with a nearly identical pharmacological profile. Its deduced amino acid sequence
      confirms that it is a member of the superfamily of G-protein-coupled receptors
      (GPR). Transcripts for the receptor are expressed in parathyroid and other
      tissues that sense Ca2+o (viz., kidney and thyroidal C-cells) as well as those
      that have no known role in extracellular Ca2+ homeostasis, such as the brain. The
      availability of the cDNA clone for the Ca2+o-sensing receptor made it possible to
      test the hypothesis that mutations in the gene encoding the human homolog of the
      receptor cause inherited disorders of mineral ion metabolism. Familial
      hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT)
      are, in fact, caused by mutations that reduce the activity of the receptor when
      they are present in the heterozygous and homozygous states, respectively. In
      contrast, we have subsequently discovered a family in which a form of autosomal
      dominant hypocalcemia results from an activating mutation in the receptor gene.
      The Ca2+-sensing receptor, therefore, permits Ca2+o to play a "hormonelike" role
      as an extracellular first messenger in addition to its well described role as an
      important intracellular second messenger.

PMID- 8579902
TI  - The effects of cytokines and growth factors on osteoblastic cells.
AB  - In this short review, some regulatory mechanisms that are involved in the control
      of normal bone formation are proposed, based on several in vivo and in vitro
      models our group has utilized recently to study osteoblast differentiation and
      mineralized bone matrix formation. Of course, these proposals must be assessed in
      the light of the limitations of the models, which probably represent a
      simplification of the complex and different ways in which normal mammalian bone
      is formed at different sites. Nevertheless, it is likely that the same general
      types of control mechanisms are active in each of the different types of bone
      formation. In adult humans, bone formation predominantly occurs by remodeling,
      the process by which bone which has recently been resorbed by osteoclasts is
      replaced by teams of osteoblasts. Other types of bone formation such as
      endochondral bone formation and appositional bone formation are also important,
      particularly during growth and adolescence. The end results of each of these
      processes are the same, namely a complex mineralized proteinaceous bone matrix.
      These processes are modulated by systemic hormonal influences, which are
      particularly important with respect to pituitary hormones and sex steroids during
      growth and adolescence, and by local cellular microenvironmental differences. The
      former will not be discussed here. Rather, we will concentrate on the local
      events and factors which are likely involved in the bone formation process
      occurring during normal bone remodeling.

PMID- 8579903
TI  - Osteoblast and chondroblast differentiation.
AB  - Recognition of discrete commitment and differentiation stages requires
      characterization of changes in proliferative capacity together with the temporal
      acquisition or loss of expression of molecular and morphological traits. Both
      cell lines and primary cultures have been useful for analysis of transitional
      steps in the chondroblast (CB) and osteoblast (OB) lineages. One striking feature
      is that OBs and CBs share expression of some molecules, including newer markers
      such as epsilon BP (galectin-3), while also having unique markers. The fact that
      hypertrophic chondrocytes appear able to downregulate cartilage markers and
      upregulate OB markers also points to an interesting lineage relationship that
      needs to be explored further. Recently, we have focused on the osteoprogenitors
      that divide and differentiate into mature OBs forming bone nodules in fetal rat
      calvaria cell cultures. We use cellular, immunocytochemical, and molecular
      approaches, including PCR on small numbers of cells, to discriminate stages.
      Nodule formation is characterized by loss of proliferative capacity and
      sequential increased marker expression, that is, alkaline phosphatase (AP),
      followed by bone sialoprotein (BSP), and osteocalcin. Upregulation of collagen
      type I and biphasic expression of osteopontin, with two peaks corresponding to
      proliferation and differentiation stages, also occurs. A variety of other
      molecules are also upregulated in the mature OB, including epsilon BP and CD44s.
      By replica plating and PCR, we have begun to study the expression of the
      messenger RNAs (mRNAs) for potential regulatory molecules (e.g., PTHrP) and their
      receptors (e.g., PTHR, FGFR-1, and PDGFR alpha) and have found all to be
      modulated during the progression from committed osteoprogenitor to mature
      OB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579904
TI  - Modulation of osteoclast differentiation by local factors.
AB  - Bone-resorbing osteoclasts are of hemopoietic cell origin, probably of the CFU-M
      derived monocyte-macrophage family. Bone marrow-derived osteoblastic stromal
      cells play an important role in modulating the differentiation of osteoclast
      progenitors in two different ways: one is the production of soluble factors, and
      the other is cell-to-cell recognition between osteoclast progenitors and
      osteoblastic stromal cells. M-CSF is probably the most important soluble factor,
      which appears to be necessary for not only proliferation of osteoclast
      progenitors, but also differentiation into mature osteoclasts and their survival.
      A number of local factors as well as systemic hormones induce osteoclast
      differentiation. They are classified into three categories in terms of the signal
      transduction: vitamin D receptor-mediated signals [1 alpha,25(OH)2D3]; protein
      kinase A-mediated signals (PTH, PTHrP, PGE2, and IL-1); and gp130-mediated
      signals (IL-6, IL-11, oncostatin M, and leukemia inhibitory factor). All of these
      osteoclast-inducing factors appear to act on osteoblastic cells to commonly
      induce osteoclast differentiation factor (ODF), which recognizes osteoclast
      progenitors and prepares them to differentiate into mature osteoclasts. This line
      of approach will undoubtedly produce new ways to treat several metabolic bone
      diseases caused by abnormal osteoclast recruitment such as osteoporosis,
      osteopetrosis, Paget's disease, rheumatoid arthritis, and periodontal disease.

PMID- 8579906
TI  - Proceedings of the International Conference on Animal Models in the Prevention
      and Treatment of Osteopenia. Cairns, Australia, February 11-13, 1995.

PMID- 8579905
TI  - The insulin-like growth factor system and the coupling of formation to
      resorption.
AB  - In the adult skeleton, bone formation is regulated by an event referred to as the
      coupling of formation to resorption (i.e., formation is linked to resorption),
      which is thought to be mediated in part by locally produced growth factors.
      Although human bone cells produce and human bones contain a variety of growth
      factors, there is sufficient evidence to document an important role for the
      insulin-like growth factor (IGF) system in mediating this coupling process in
      bone. Studies on the basic aspects of the IGF system in bone reveal that it is
      complex and involves a number of components which include the IGF-binding
      proteins (IGFBPs; mainly IGFBP-3, -4, and -5), specific extracellular IGFBP
      proteases, and receptors (types 1 and 2). Based on recent experimental evidence
      from a number of laboratories, we propose the following models of IGF action on
      the regulation of the coupled increase in bone formation in response to bone
      resorption: (1) IGF release from bone during bone resorption promotes osteoblasts
      to initiate cavity refilling; (2) IGF production by osteoclasts creates a
      population of osteoblasts in proportion to the volume of bone tissue resorbed;
      and (3) IGF production by stromal cells and osteoblasts predominantly regulates
      the extent of cavity refill. The amount of growth factor production by
      osteoblasts and contemporary cells of osteoblast lineage can be further
      controlled by both systemic and local factors which together determine the
      eventual level of fill-in of the resorption cavity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8579907
TI  - Available animal models of osteopenia--small and large.
AB  - Animal models of osteopenia are reviewed. Endocrine excess or deficiency
      conditions include ovariectomy, orchidectomy, glucocorticoid excess and other
      endocrine states. Seasonal and reproductive cycles are usually transient and
      include pregnancy and lactation, egg-laying, antler formation and hibernation.
      Dietary conditions include calcium deficiencies, phosphate excess and vitamin C
      and D deficiencies. Mechanical usage effects include skeletal underloading
      models. Aging is also associated with osteopenia in many species.

PMID- 8579908
TI  - FDA Guidelines and animal models for osteoporosis.
AB  - The recent FDA Guidelines For Preclinical and Clinical Evaluation of Agents Used
      in the Treatment or Prevention of Postmenopausal Osteoporosis (1994) delineate
      specific preclinical animal models to demonstrate the efficacy and safety of new,
      potential agents for osteoporosis therapy. The Guidelines recommend that agents
      be evaluated in two animal species, including the ovariectomized (OVX) rat and in
      a second non-rodent model. We have performed a series of studies to determine
      whether the recommended OVX rat models, endpoints, and study design adequately
      address the efficacy and safety of therapeutic agents for the treatment or
      prevention of osteoporosis. Our study results indicate that the rat OVX model
      mimics postmenopausal cancellous bone loss when examined over relatively short
      periods of time. These data illustrate that cancellous bone turnover increases
      following OVX and this increased bone turnover produces bone loss. Estrogen
      completely blocks the activation of bone turnover and bone loss. Thus, our data
      suggest that the rat OVX model in the proximal tibia, distal femur, and lumbar
      vertebrae mimics conditions in the postmenopausal woman and is suitable for the
      evaluation of potential therapeutic agents for the prevention of osteoporosis.
      However, when the duration of the studies extends to 12 months as suggested by
      the Guidelines, the indices of cancellous bone turnover return to the value of
      sham controls, although the trabecular bone volume remains lower than that of
      sham controls in OVX rats. Therefore, it is difficult to determine the effects of
      potential therapeutic agents on the bone turnover in estrogen deficient
      conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579909
TI  - Evolution of the pathogenesis of postmenopausal bone loss.
AB  - At a time when the investigation of bone diseases appears to be on the threshold
      of a new era, it is appropriate to pause and contemplate past and present
      thinking on the etiology of postmenopausal osteoporosis. This brief review traces
      the evolution of ideas on the nature of the pathogenesis of this disease from
      Albright's hypoosteoblastic hypothesis through other hypotheses that include
      disturbance in osteoclasia, negative calcium balance, disturbance of calcium
      homeostatic control mechanisms, increased skeletal sensitivity to parathyroid
      hormone, deficiency of calcitriol and calcitonin, altered activities of growth
      factors and cytokines, alterations in the local regulation of osteoclastogenesis,
      and changes in mechanical usage set points.

PMID- 8579910
TI  - Assessing bone quantity by pQCT.
AB  - We have tested the ability of the XCT960A to detect bone loss in OVX-rats, as
      well as bone gain in the proximal tibial metaphysis of healthy rats treated with
      hPTH(1-34). The results demonstrated that high precision can be achieved, with
      CV's for most measurement parameters in the range of 1.6 to 5.9% being obtained
      in vivo with repositioning of animals. Significant changes in bone parameters in
      the tibia were observed already at 2 weeks following OVX or PTH-therapy, while
      whole bone mass measured in the tibia by DEXA ex vivo did not change
      significantly for up to 24 weeks. For the proximal rat tibia at location 5mm
      distal to the knee joint was identified as an optimal site. At this location,
      cortices are fairly parallel thus reducing the partial volume effect, the area is
      relatively rich in cancellous bone increasing the magnitude of bone gain or loss,
      and the site (2mm below the growth plate) is relevant for comparisons with
      histomorphometric measurements. The results demonstrate that pQCT can be adapted
      for use in small animals such as rats, and that it is a sensitive, reproducible,
      non-invasive method available to monitor changes in bone mass, bone density, and
      geometric properties. Future studies should help to establish whether the moment
      of inertia, moment of resistance and the newly added bone strength index provided
      by the machine are predictive in any way for bone strength as obtained from
      biomechanical testing procedures. Peripheral QCT in small animals is an important
      addition for drug evaluation because it is more sensitive than DEXA and allows
      for shorter duration of experiments. This non-invasive method can reliably
      measure changes in cancellous and cortical bone mass over time following
      ovariectomy or administration of the bone anabolic hormone hPTH(1-34). pQCT
      should be viewed as a complimentary technique to static and dynamic
      histomorphometry, which does not replace either of these methods. Its value in
      the field of basic research should be evaluated.

PMID- 8579911
TI  - Comparative x-ray densitometry of bones from ovariectomized rats.
AB  - Comparative analysis of dual energy x-ray absorptiometry (DXA) and quantitative
      computed tomography (QCT) with phantoms and rat bones showed that both are
      necessary to adequately quantitate ovariectomy induced bone changes, in vivo.
      Precision and accuracy analysis of a Hologic QDR 1000/W and a Stratec 960 QCT
      showed that the latter is a highly precise, modestly accurate device that is more
      suited to the analysis of small bones. Specifically, smaller error was achieved
      by threshold optimization for the QCT in the analysis of phantoms 1.04-9.6 mm in
      diameter, with precision comparable to or better than DXA. Additionally, the QCT
      measured significant differences between groups in proximal tibiae when DXA could
      not; and measured a larger difference between sham and ovariectomized controls
      which was suitable for analysis of the dose dependent effects of a
      pharmacological test compound, raloxifene. This may reflect the ability of the
      QCT to measure volumetric mineral density (VMD, mg/cc), compared to two
      dimensional analyses by DXA. However, QCT was not able to analyze vertebrae in
      vivo, a site of considerable clinical interest. Therefore, DXA is useful to
      analyze the axial skeleton in vivo, while the appendicular skeleton is better
      analyzed in vivo by QCT. By both techniques, a similar dose response was observed
      for raloxifene, with ED50 = 0.3 mg/kg for both axial and appendicular skeleton.
      Comparative analysis of rat L1-4 by the Hologic QDR 1000/W and Lunar DPXL showed
      12-14% higher BMD and BMC values for the Hologic, which is the opposite
      relationship between these instruments to that observed clinically for this site.

PMID- 8579912
TI  - The effect of ovariectomy on bone metabolism in rats.
AB  - It is well known that the ovariectomized rat is a good model for osteoporosis.
      Recently, it has been possible to measure the bone mineral density (BMD) of small
      animals accurately using dual energy X-ray absorptiometry (DXA). Therefore, in
      this study the change in the BMD in the different bone structures was examined in
      in vivo using aged and growing rats. The BMD of the lumbar spine and the tibial
      proximal metaphysis, which are mainly trabecular bone, in ovariectomized aged and
      growing rats with ovariectomized was significantly lower than those of the
      control (sham) group. However, the BMD of the tibial diaphysis, which is mainly
      cortical bone, showed no change nor had a tendency to decrease in the early
      stages of the experiment. These results suggest that it is important to take into
      account the age and the bone site in order to evaluate the experiment, which uses
      the rat model with ovariectomized osteoporosis.

PMID- 8579913
TI  - The effect of oophorectomy on calcium homeostasis.
AB  - Postmenopausal bone loss is associated with a rise in the fasting urine calcium
      excretion which has been proposed to be a possible cause of increased bone
      resorption. The oophorectomized rat is widely used as a model of postmenopausal
      bone loss, but preliminary data suggest that urine calcium excretion is not
      increased following oophorectomy in this animal model. However the present
      detailed experimental protocol demonstrated that oophorectomy in adult rats
      increased the obligatory urine calcium excretion compared with ovary-intact rats
      (P < 0.001). Importantly urine hydroxyproline excretion was positively correlated
      with urine calcium only in the oophorectomized rats (P = 0.003). This urine
      calcium was positively correlated with urine phosphate excretion when dietary
      sodium was low (P < 0.001) and with urine sodium excretion when dietary sodium
      was elevated (P = 0.003). Calcium balance studies indicated a greater fall in
      calcium accretion in growing, oophorectomized rats (6 to 15 weeks of age)
      compared with ovary-intact animals and intestinal calcium secretion was the major
      component of the calcium balance to be affected. Losses of calcium in the urine
      were relatively minor in these growing rats.

PMID- 8579914
TI  - Droloxifene inhibits cortical bone turnover associated with estrogen deficiency
      in rats.
AB  - Droloxifene (DRO), an estrogen antagonist/agonist, has been shown to possess
      estrogen-like effects in inhibiting bone turnover leading to cancellous bone loss
      in ovariectomized (OVX) rats. The purpose of this study was to determine the
      effects of DRO on cortical bone turnover in OVX rats. Sprague-Dawley female rats
      at 5 months of age were sham-operated (sham, n = 8) and orally treated with
      vehicle, or OVX (n = 56) and orally treated with either vehicle, DRO at 0.1, 1,
      5, or 10 mg/kg/day, or 17 alpha-ethynyl estradiol (EE) at 3 or 30
      micrograms/kg/day for 4 weeks. Static and dynamic cortical bone histomorphometry
      was performed on double fluorescent labeled, undecalcified cross sections of
      tibial diaphyses (proximal to the tibiofibular junction). There were no
      significant differences in tibial diaphyseal cross sectional area, marrow cavity
      area, and cortical bone area between groups after 4 weeks of administration.
      Periosteal mineralizing surface, mineral apposition rate, and bone formation rate
      surface referent and endocortical eroded surface increased significantly, while
      endocortical mineral apposition rate and bone formation rate-surface referent
      increased nonsignificantly in OVX controls compared to sham controls. Treatment
      with DRO at doses of 0.1 to 10 mg/kg/day dose-dependently attenuated the OVX
      induced higher bone formation indices in both the periosteal and endocortical
      surfaces and higher bone resorption index in the endocortical surface. At the
      highest dose (10 mg/kg/day), DRO completely inhibited the increases in bone
      formation and resorption indices in OVX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579915
TI  - Tissue-selective actions of estrogen analogs.
AB  - The biological actions of estrogen analogs have frequently confounded prevailing
      views regarding the mechanism of estrogen action. Agents originally intended as
      antifertility drugs are now used clinically to promote ovulation. The early work
      with antiestrogens as antifertility agents lead to the realization that
      triphenylethylene antiestrogens suppressed the growth of breast tumors. The
      subsequent ubiquitous clinical use of tamoxifen for adjuvant breast cancer
      therapy is a direct result of this research. Basic studies using tamoxifen and
      related antiestrogens revealed the previously unsuspected tissue selective
      actions of these compounds. This peculiar property is being taken advantage of to
      gain new insight into the molecular mechanisms of estrogen action. This property
      also forms the basis for an exciting new approach to hormone replacement therapy
      to prevent postmenopausal osteoporosis and cardiovascular disease. The laboratory
      rat played an integral and essential part in each of these developments. The
      success of the ovariectomized rat model in predicting the tissue selective
      effects of tamoxifen in women greatly increases confidence that this animal model
      will be useful in development of a new generation of estrogen analogs designed
      specifically for postmenopausal hormone replacement.

PMID- 8579916
TI  - The ferret as a small animal model with BMU-based remodeling for skeletal
      research.
AB  - The need exists for a small animal model with bone metabolic unit (BMU)-based
      remodeling to mimic the bone loss found in postmenopausal women. The purpose of
      this investigation was to evaluate the ferret as a potential model for skeletal
      research. Specifically, we determined whether the ferret: 1) exhibits evidence of
      BMU-remodeling, 2) has a skeletal response to parathyroid hormone (PTH) similar
      to other remodeling species, and 3) loses bone in response to reduced estrogen
      levels. METHODS: Using three sets of experiments, we determined the response of
      female ferrets to ovariectomy/light cycle manipulation or to administration of
      PTH. Scanning electron microscopy, light microscopy, determination of estrogen
      levels and/or single-photon absorptiometry (SPA) were used for evaluation.
      RESULTS: The ferret was found to exhibit BMU-based remodeling, and may therefore
      provide a small animal remodeling species for skeletal research. Ferrets reach
      skeletal maturity between four and seven months of age as evidenced by closure of
      the growth plate and maturation of trabecluae from thin rods to thick rods and
      plates. PTH treatment resulted in a marked increase in bone mass accompanied by
      the PTH-induced tunneling phenomenon known to occur in dogs and humans but not
      rats. The response to PTH supports the use of the ferret in studies of bone
      anabolic agents. Bone mass in the proximal tibia was significantly reduced when
      estrogen depletion was induced by either bilateral ovariectomy or short
      light/dark cycles (8 hour light, 16 hour dark). Maintenance of intact ferrets
      under short-light conditions mimiced ovariectomy in terms of serum estrogen
      levels, uterine weights, and tibial BMD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579917
TI  - Skeletal adaptations to mechanical usage: results from tibial loading studies in
      rats.
AB  - Wolff's law defines a static relationship between stress trajectories and
      trabecular architecture. More recent theories have attempted to describe the
      dynamic relationship between the form of bone and its mechanical environment.
      Frost's mechanostat theory is unique among these in its distinction between
      modeling and remodeling processes, lamellar and woven bone formation, mechanical
      usage windows for activation and its application to disorders of bone and mineral
      metabolism. Our studies suggest that lamellar and woven bone formation are very
      different not only in histological appearance, but in the temporal
      characteristics of their formation. Thus, it is important to distinguish these
      two histological types when interpreting studies of adaptive bone formation.
      Studies using the in vivo 4-point bending model in rat tibiae show that static
      loads do not play a role in mechanotransduction and that bone formation is
      threshold-driven and dependent on strain rate, amplitude and duration of loading.
      They have also provided strong indirect evidence that mechanical strains cause
      interstitial fluid flow that, in turn, activates the bone cell response. Based on
      these observations, we hypothesize that strain rate determines the vigor of
      osteoblastic activity and the regularity of loading bouts determines osteoblast
      recruitment in a "quantum" fashion.

PMID- 8579918
TI  - Adaptation of non-growing former epiphysis and metaphyseal trabecular bones to
      aging and immobilization in rat.
AB  - No data exit for distal tibia (DT), a bone site with growth plate closure at 3
      months of age and with very low trabecular bone turnover rate. The purpose of
      this study was to characterize the response of DT to aging and immobilization
      (IM) in 6 to 16.5 month-old female rats. One hundred and forty six 6 month-old
      Sprague-Dawley rats were divided into aging controls and right hindlimb
      immobilization (RHLI) groups. The right hindlimb was immobilized against the
      abdomen with elastic bandages. Rats were sacrificed serially from 6 to 16.5
      months old at intervals of 2 to 8 weeks. The histomorphometric study was
      performed on areas of former epiphyseal and metaphyseal trabecular bone of DT. No
      changes on bone mass or architecture were found in aging controls throughout the
      study. There was a decrease in bone mass of the former epiphysis after 3.5 months
      of IM due to resorption exceeding formation. Then it reverted to the aging
      control level at 4 months post IM. At the former metaphyseal site, significant
      bone loss (-19%) was observed as early as two weeks after IM. The peak bone loss
      (-54%) was reached at 1.5 months after IM and plateaued thereafter. The bone loss
      was mainly due to the reduction of trabecular thickness although trabecular
      number decreased significantly after 3.5 months IM. These results suggest that
      both former epiphysis and metaphyseal trabecular bones in DT can quickly adapt by
      losing bone to immobilization.

PMID- 8579919
TI  - Remobilization partially restored the bone mass in a non-growing cancellous bone
      site following long term immobilization.
AB  - There is no report in the rat of the effects of remobilization (RM) in an adult
      bone site. The aim of this study was to determine whether complete recovery from
      IM-induced bone loss will occur in a non-growing bone site, the distal tibia.
      Seventy-five 6-month-old virgin Sprague-Dawley female rats were used in this
      study. Their hindlimbs were immobilized against the abdomen with bandages for 18
      weeks, then remobilized for 2, 10 or 20 weeks. Distal tibial sections were
      analyzed in the former epiphysis, 0.3 mm proximal from the calcified cartilage,
      and in trabecular bone of the former metaphysis between 0.3 mm and 1.92 mm
      proximal to the former epiphysis. A significant bone loss occurred in both former
      epiphyseal and metaphyseal trabeculae at 18 weeks after IM. The lost bone was
      partially recovered at 10 weeks of RM, but the bone mass was still lower than in
      aging controls by the end of the study. The partial recovery was characterized by
      decreasing former epiphyseal bone porosity and thickening of former metaphyseal
      trabeculae with no effect on trabecular number. We concluded that both distal
      tibia regions only partially recovered, during 20 weeks of RM from the long time
      IM.

PMID- 8579920
TI  - Parathyroid hormone therapy accelerates recovery from immobilization-induced
      osteopenia.
AB  - Previous reports have shown that bone mass and architecture will partially
      recover by remobilization (RM) in immobilization (IM)-induced osteopenia. The aim
      of this study was to test whether PTH can accelerate the recovery during RM from
      the IM-induced osteopenia. Six-month-old Sprague-Dawley female rats were divided
      into aging and IM groups. The right hindlimb of rats was immobilized against the
      abdomen by elastic bandages for 18 weeks, then groups of rats were further IM or
      RM for 2, 10 and 20 weeks and given 30 or 80 micrograms hPTH (1-38)/kg/d s.c.
      Secondary spongiosa of proximal tibial metaphyses (PTM) were studied.
      Immobilization reduced the trabecular area, number and thickness at the first 18
      weeks post IM, then plateaued. Ten weeks of RM restored 40% trabecular bone from
      IM controls due to thickening of the trabeculae. However, the trabecular area was
      still -14% and -13% lower than that of aging controls at 10 and 20 weeks. Two
      weeks of 30 micrograms PTH/kg/d in IM rats restored the bone to aging control
      levels, two weeks of 30 micrograms PTH/kg/d in RM rats and of 80 micrograms
      PTH/kg/d in both RM and IM rats added extra bone. Extending the treatment to 10
      and 20 weeks, the same amount of total bone was added to both IM and RM rats.
      These findings indicate PTH is a powerful agent that can accelerate the recovery
      and add extra bone to osteopenic cancellous bone in both IM and RM rats.

PMID- 8579921
TI  - The effect of pamidronate in a new model of immobilization in the dog.
AB  - Bone loss resulting from immobilization or disuse has been shown in humans
      following paralysis or bedrest. We have developed a new model of immobilization
      in the dog which is reversible and we have studied the effect of pamidronate
      (APD) in this model. Twelve mature beagle dogs were fitted with specially
      designed mesh jackets. These jackets were used to bind the left forelimb against
      the body of the dog, thereby preventing weight bearing on that limb. The
      experimental group (n = 6) was treated with an I.V. dose of 0.45 mumol/kg/day APD
      (pamidronate) for 7 days followed by 3 weeks without treatment. This cycle was
      repeated 3 times for a total of 12 weeks. The control group (n = 6) followed the
      same pattern, but received only saline injections. At the end of the experiment,
      the dogs were sacrificed and the humeri and radii cleaned of soft tissues.
      Mineralization profiles, which determine the distribution of mineralization
      densities of the cortical and trabecular bone were obtained and the main
      fractions were analyzed chemically. Static histomorphometric parameters were
      determined on 5 microns undecalcified sections from the distal humerus and on 50
      microns section of the humeral shaft. Three point bending and torsional testing
      were performed on the radius. Immobilization induces hypomineralization in
      cortical and cancellous bone but is prevented by APD treatment in cancellous.
      Immobilization in this model induces osteopenia and increases turnover in
      cancellous bone. These effects are counteracted by APD. Finally, cortical bone
      density and stiffness are reduced by immobilization but this is prevented by APD
      treatment. This experiment shows that the mature dog model is useful to study the
      immobilization-induced increase of bone turnover and concomitant decrease in bone
      density, stiffness and mineralization. It also shows that these effects of
      immobilization can be prevented by treatment with the bisphosphonate pamidronate.

PMID- 8579922
TI  - Tomographic (pQCT) and biomechanical effects of hPTH(1-38) on chronically
      immobilized or overloaded rat femurs.
AB  - Six-month old rats chronically submitted to right hindlimb immobilization (IM)
      with mechanical overload (OL) of the left leg were treated 1 month later with 200
      micrograms/kg/d of hPTH(1-38) for 15 or 75 days. Peripheral quantitative computed
      tomography (pQCT) scans and bending tests showed that hPTH increased cortical
      mass and volumetric BMD (vCtBMD) in both legs. However, elastic modulus of
      cortical bone and diaphyseal load-bearing capacity were improved only in OL
      bones. Improvement of diaphyseal strength was attributable to that of cortical
      bone quality, yet a stronger mechanostatic response of cortical modeling to bone
      material quality was also observed in treated OL bones. Data support hPTH(1-38)
      use for improving cortical bone mass and strength and point out a physical
      activity interaction with therapeutic results.

PMID- 8579923
TI  - An in-vivo model for the rapid assessment of skeletal effects of anabolic agents.
AB  - We recently developed an in vivo model which can be used to rapidly assess the
      local skeletal effects of anabolic agents. In this model, 160 g Sprague-Dawley
      (SD) rats were used. A stainless steel cannula was inserted into the marrow
      cavity of the proximal tibia through the anterior-medial cortex 6 mm distal to
      the knee joint. The outer opening of the cannula was covered by skin. Agents with
      known anabolic skeletal effects or vehicle were injected daily for 10 days into
      the marrow region by a small needle passing through the cannula. Rats were also
      injected subcutaneously with a fluorescent bone marker to label the newly formed
      bone. Injection sites were fixed, embedded, and sectioned for histomorphometric
      analysis of trabecular bone. PTH and PGE2 stimulated a large amount of new
      trabecular bone formation in regions proximal and distal to the injection site as
      measured by histomorphometry. Control groups showed minimal bone formation,
      limited to formation of a thin layer of bony shell immediately surrounding the
      cannula. The profound anabolic skeletal effects of PTH and PGE2 seen in this
      Local Injection Model are similar to those seen in systemic injection (i.e.
      subcutaneous injection in intact or castrated male and female rats) previously
      reported. This Local Injection Model combines numerous advantages of in vivo
      models (systemic injection) and in vitro models when assessing agents with
      anabolic skeletal activities. Compared to conventional in vivo systemic injection
      models, this model enables detection of anabolic skeletal effects using very
      small quantities (in microgram) of test agents in a short treatment period (< 10
      days).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579924
TI  - An in vivo model for the rapid assessment of the local effects of parathyroid
      hormone on bone histomorphometry.
AB  - The process of bone remodelling is likely to be controlled to a large extent by
      factors acting locally in a paracrine or autocrine manner, along with some
      systemic control. In our laboratory we routinely use an in vivo model in which
      the local effects of factors on bone histomorphometry can be determined. The
      factor under investigation is injected just above the periosteum of the right
      hemicalvaria in the adult male mouse. These subcutaneous injections are given
      daily over a 1-week period and the animals sacrificed at intervals after the last
      injection. With appropriate staining techniques it is possible to determine the
      effects of a particular agent on osteoblast and osteoclast numbers; the area of
      total bone, mineralized bone, osteoid and periosteum; osteoblast, osteoclast and
      eroded surfaces, and thus to infer the rate of bone formation and bone resorption
      in the right hemicalvaria compared to the uninjected left hemicalvaria and to
      vehicle-injected control animals. All these parameters are measured using a bone
      dedicated image analyzer. Utilizing this in vivo model, we and others have
      studied a number of bone-active factors. We report the effects of parathyroid
      hormone, as well as reviewing results of our studies of leukemia inhibitory
      factor, amylin, calcitonin and calcitonin gene-related peptide in the model. The
      results obtained are similar to those found in most other animal models and in
      man. In conclusion, we describe an in vivo model whereby bone-active factors,
      injected locally, can be rapidly assessed.

PMID- 8579925
TI  - Early effects of prostaglandin E2 on bone formation and resorption in different
      bone sites of rats.
AB  - The aim of this study was to determine early effects of prostaglandin E2 (PGE2)
      on bone mass, formation and resorption in a growing cancellous bone site (the
      proximal tibial metaphysis, PTM), non-growing cancellous bone site (the distal
      tibial metaphysis, DTM), and cortical bone site (the tibial shaft, TX) with
      histomorphometric analysis. Six mg PGE2/kg/d was given s.c. to 6-month-old
      Sprague-Dawley female rats for 5, 10 or 16 days. Double fluorescent labels were
      given to 0, 10- and 16-day PGE2 treatment and 16-day control groups. Significant
      increase in bone mass was found after 16 days treatment in cancellous bone sites
      but not in the cortical bone site. Stimulated bone formation, indicated by the
      increase in osteoid perimeter, was observed as early as 5 days post-treatment in
      all 3 bone sites. Bone formation indices were increased after 10 days of
      treatment, however, there was no difference in selected bone formation indices
      between 10 and 16 days PGE2 treatments at all 3 bone sites. Significant increase
      in eroded surface and eroded surface covered with osteoid was observed in
      cancellous bone sites after 5 days, but decreased after 10 days of treatment.
      Although the eroded surface was not elevated in TX at the 5th day, the eroded
      surface covered with osteoid was increased on endocortical surface which
      indicated that PGE2 stimulated bone resorption on this surface prior to day 5. We
      concluded that PGE2 stimulated the bone formation and resorption as early as 5
      days post-treatment. The levels of stimulated bone formation was TX > DTM >
      PTM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579926
TI  - Risedronate pretreatment does not hamper the anabolic effects of prostaglandin E2
      in ovx rats.
AB  - Pretreatment of an anti-resorptive agent on the anabolic effects of prostaglandin
      E2 (PGE2) was studied on the proximal tibia and tibial shaft of ovariectomy (ovx)
      rats. Two days after ovx, rats were treated with either risedronate (Ris, 5
      micrograms/kg twice weekly) or vehicle (V) for 60 days and then switched to 3 or
      6 mg/kg/d PGE2 for 21 or 90 days. Bone area of both proximal tibial metaphysis
      (PTM) and tibial shaft (TX) were measured. Pretreatment with Ris increased the
      bone mass in PTM but not in TX of ovx rats. In the PTM, PGE2 produced the same
      percentage of new bone mass in both V- and Ris-pretreated ovx rats. The amount of
      new bone was almost the same after 3 weeks and 12 weeks of PGE2 treatment. There
      was no difference in the anabolic effects of 3 and 6 mg PGE2/kg/d in V-pretreated
      rats; however, the effects in Ris-pretreated groups were greater with 6 mg
      PGE2/kg/d than with 3 mg PGE2/kg/d. In TX, only the 6mg PGE2/kg/d administration
      added new bone on endocortical surfaces of both V- or Ris-pretreatment rats which
      leads to thickening the minimal cortical width, decreasing the marrow cavity and
      increasing total bone area. Both doses of PGE2 created new trabecular bone in the
      marrow cavity of tibial shaft in both vehicle- and Ris-pretreated ovx rats. These
      results suggest that Ris-pretreatment did not hamper the anabolic effects of PGE2
      on either PTM or TX in ovx rats.

PMID- 8579927
TI  - Co-treatment of PGE2 and risedronate is better than PGE2 alone in the long-term
      treatment of ovariectomized-induced osteopenic rats.
AB  - We studied the effects of prostaglandin (PGE2) and risedronate (Ris) alone or in
      combination in 3.5-month-old intact and ovx-induced osteopenic rat skeletons to
      determine whether PGE2 plus Ris was more anabolic than PGE2 alone. Six mg
      PGE2/kg/d and 5 micrograms Ris/kg/2x/wk alone or in combination were given to
      sham-ovx and ovx rats for 30 or 90 days beginning 60 days post operation.
      Secondary spongiosa of proximal tibial metaphyses (PTM) was studied. Ovariectomy
      (ovx) induced dramatic bone loss. Ris increased bone mass in sham-ovx rats and
      prevented further bone loss in ovx rats. PGE2 treatment for 30 days added extra
      bone in sham-ovx rats and no further increase after 90 days treatment. Thirty
      days of PGE2 alone treatment restored the bone mass in ovx rats to the level of
      sham-ovx rats, but the restored bone was partially lost by 90 days of treatment.
      Co-treatment for 30 days produced the same amount of bone mass in both sham-ovx
      and ovx rats as PGE2 alone did. However, unlike the PGE2 alone treated, co
      treatment animals continued to form more bone for 90 days. The difference in
      tissue-level histomorphometry between co-treatment and PGE2 alone was that the
      former depressed the bone resorption and turnover. These findings indicated that
      the long-term administration of PGE2 alone cannot maintain or continue to add
      bone mass in ovx rats but that co-treatment of a PGE2 with an anti-resorptive or
      activation agent can resist the influence of the mechanostat induced bone loss as
      well as continue to add bone.

PMID- 8579928
TI  - A histomorphometric study on effects of single and concurrent intermittent
      administration of human PTH (1-34) and bisphosphonate cimadronate on tibial
      metaphysis in ovariectomized rats.
AB  - This study compared the single administration of hPTH(1-34), bisphosphonate
      cimadronate (YM-175), and concurrent therapy of these two for restoration of lost
      bone mass in ovariectomized (OVX) rats. Animals were untreated for 4 weeks after
      surgery, and then injected s.c. with vehicle (OVX+V), hPTH(1-34) (30
      micrograms/kg) (OVX+P), YM-175 (5 micrograms/kg) (OVX+Y), or a combination of
      these two (OVX+P+Y), 3 days a week, for 8 weeks, and sacrificed. Their proximal
      tibia were processed undecalcified for quantitative bone histomorphometry.
      Although OVX+Y showed a reduction of bone turnover compared to OVX+V, it failed
      to restore lost bone mass in OVX rats. In contrast, OVX+P exhibited a stimulation
      of bone formation and restored cancellous osteopenia due to OVX. OVX+P+Y also
      resulted a recovery of osteopenia, however, stimulation of bone formation by PTH
      was suppressed by YM-175.

PMID- 8579929
TI  - Discrepancy of response of hPTH administration and its withdrawal between
      trabecular and cortical bone sites in OVX rats.
AB  - We demonstrated the differences of response between trabecular and cortical bone
      sites in the rat induced by OVX and hPTH(1-34) administration [subcutaneous
      injection, 30 micrograms/kg, 3 times/week, for 12 weeks] and its withdrawal [for
      8 weeks]. We observed that hPTH(1-34) administration in OVX rats partially
      prevented OVX-induced cancellous bone loss in the proximal tiabial metaphysis and
      added cortical bone in the tibial shaft. After cessation of hPTH treatment, bone
      loss was observed both in trabecular and cortical bone; however, it was more
      dramatic on endocortical surfaces.

PMID- 8579930
TI  - Intermittent treatment of prostaglandin E2 with risedronate is more anabolic than
      prostaglandin E2 alone in the proximal tibial metaphysis of ovariectomized rats.
AB  - This study is designed to test how intermittent application of prostaglandin E2
      (PGE2) and risedronate (Ris) alone or in combination acts on the cancellous bone
      mass in estrogen-deficient rats. Sprague-Dawley rats were ovariectomized (ovx) or
      sham-ovx'd at 6 months of age. PGE2 (6mg/kg/d), Ris (5 micrograms/kg/twice a
      week) or PGE2 plus Ris were given for 60 days to ovx rats immediately after
      operation and followed by 60 days without treatment. The drugs were then
      reapplied for another 60 days. Static histomorphometry was performed on the
      secondary spongiosa of proximal tibial metaphysis (PTM). Sixty days of ovx lost
      trabecular bone and number, Ris prevented ovx-induced bone loss. PGE2 added 48%
      extra cancellous bone, but the new bone was completely lost after 60 days of
      withdrawal. Another 60 days of PGE2 treatment only partially restored the
      trabecular bone, the bone mass was still -42% lower than that of sham-ovx
      controls. Co-treatment of PGE2 with Ris added the same amount of bone as PGE2
      alone after the first 60 days treatment period, but differed from PGE2 alone in
      that the new bone lost less during the 60 days withdrawal period. Re-application
      of co-treatment for another 60 days added more extra bone. We concluded that
      intermittent co-treatment with anabolic and anti-resorptive agents is more
      effective than anabolic agent alone in long-term therapy of cancellous bone in
      estrogen-deficient rats.

PMID- 8579932
TI  - Animal models of cortical porosity.
AB  - Increased cortical porosity (Ct.Po) has been observed as a consequence of aging,
      disease (hyperparathyroidism, osteoporosis), and pharmacologic intervention
      (thyroid hormone, fluoride, parathyroid hormone, prostaglandins). Whether this is
      permanent or transient in humans has not been established nor has the impact of
      Ct.Po on bone strength or fracture incidence been determined. There is a need to
      understand the causes and consequences of increased Ct.Po and how it relates to
      disease states and osteoporosis therapies. The mechanism of increased Ct.Po is
      thought to be an increased activation of Haversian remodeling systems accompanied
      by increased Haversian canal diameter. Increased activation at the endocortical
      surface and subsequent trabecularization may also contribute to loss of cortical
      bone. Ct.Po has been observed in several animal models which can be used to
      further study the phenomenon. Ct.Po is seen in normal dogs and is increased by
      treatment with PTH and prostaglandins. In the dog it has also been shown that
      increased Ct.Po is reversible after anabolic therapy is discontinued.
      Furthermore, in dogs an antiresorptive agent (risedronate) will block PTH-induced
      increases in Ct.Po (control 1.6% +/- 0.7; PTH 3.0% +/- 1.1, PTH plus risedronate
      1.8% +/- 1.2) without interfering with anabolic effects. In rats, increased Ct.Po
      occurs following treatment with anabolic agents such as PTH, prostaglandin, and
      insulin-like growth factor 1 (IGF-1). For instance, with IGF-1, Ct.Po increased
      from 0.4% +/- 0.4 to 5.4% +/- 1.8. Other species in which Ct.Po is observed
      include primates and ferrets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579931
TI  - Intermittent treatments of prostaglandin E2 plus risedronate and prostaglandin E2
      alone are equally anabolic on tibial shaft of ovariectomized rats.
AB  - Effects of intermittent administration of prostaglandin E2 (PGE2), risedronate
      (Ris) and their combination on bone mass were studied on the cortical bone of
      tibial shafts of ovariectomized (ovx) rats. Six month old ovx rats were treated
      immediately after operation with subcutaneous injections of 6 mg PGE2/kg/d, 5
      micrograms Ris/kg/2x/wk or their combination for 60 days each of an on/off/on
      cycle. PGE2 alone and in combination with Ris added the same amount of new bone
      in the first 60 days on period. During the 60 days off period, newly added
      endocortical and marrow trabecular bone disappeared in PGE2 alone treatment
      groups. In co-treatment group, the marrow trabeculae were only partly lost. There
      was no difference in total bone area between co-treatment and PGE2 alone groups
      after another 60 days on treatment. Our findings indicate that co-treatment was
      better in the maintenance of newly added endocortical and marrow trabecular bone
      during the off period; however, it formed less bone than PGE2 alone during the
      second treatment period, and ended up with the same amount of bone with both
      treatments.

PMID- 8579933
TI  - Maintenance therapy for added bone mass or how to keep the profit after
      withdrawal of therapy of osteopenia.
AB  - Since continuous therapy for osteoporosis can be expensive and may have
      detrimental effects, there is a need to develop a strategy to maintain bone mass
      after withdrawal of treatment. The bone maintained by estrogen and calcitonin
      therapies and exercise, but the added bone induced by anabolic agents disappears
      upon cessation of treatment. To avoid this pitfall, the concepts of activation,
      restore and maintain (ARM) or loss, restore and maintain (LRM), the on/off
      administration of combined anabolic agent with an antiresorptive or
      antiactivation agent, and cyclical treatment of the two regimes have been
      employed successfully in "keeping the profit" (maintaining bone) in preclinical
      studies. The data for the disappearance of bone upon cessation of certain
      osteopenic treatments, its mechanism of loss and the development of maintenance
      concept and subsequent preclinical studies indicate that there was no need for
      costly continuous therapy in the treatment strategy for osteoporosis.

PMID- 8579934
TI  - Effects of on/off anabolic hPTH and remodeling inhibitors on metaphyseal bone of
      immobilized rat femurs. Tomographical (pQCT) description and correlation with
      histomorphometric changes in tibial cancellous bone.
AB  - An anabolic effect of hPTH(1-38) (s.c. doses of 200 micrograms/kg/d during 75
      days) on trabecular and cortical bone mass is tomographically described in the
      metaphyseal region of immobilized rat femurs using pQCT technology, in agreement
      with previous histomorphometrical studies of the proximal tibial metaphyses.
      Correlations between pQCT and histomorphometrical data showed that this effect
      derived from a stimulation of endosteal and trabecular bone modeling that induced
      a transference from trabecular to cortical bone mass. Loss of effects after
      withdrawal, resulting from a stimulation of bone remodeling, could be total or
      partially prevented by subsequent s.c. injections of risedronate (5
      micrograms/kg/2/wk), 17-B-estradiol (10 micrograms/kg/d) or calcitonin (10
      micrograms/kg/d) given during 60 days, in this order of effectiveness. The
      preventive potency was proportionally related to the reduction induced in
      histomorphometric indices of bone resorption.

PMID- 8579935
TI  - Estrogen dose required to maintain parathyroid hormone mediated bone gain in
      osteopenic ovariectomized rats is probably higher than in preventive treatment
      with estrogen.
AB  - Successful prevention of bone loss in ovariectomized rats with 17 beta-estradiol
      (E2) at 10 micrograms/kg/d has been reported. Here we show that E2 dose twice
      that much is not enough to maintain PTH(1-34) mediated bone gain. Three-month-old
      female Wistar rats were ovariectomized and fed with regular rodent chow and water
      ad libitum. Three months later they were divided into 9 groups (5-8 per group)
      and treated cyclically with PTH(1-34) (20 micrograms/kg/d sc, 5d/w for 3w) and E2
      (20 micrograms/kg/d sc, 5d/w for 4w). There were also a baseline group and five
      vehicle control groups. Cancellous bone volume (Cn.BV/TV) of distal femoral
      metaphyses was measured by computer-aided histomorphometry on trichrome stained
      thin sections, and 24-hour fasted urine was analyzed for pyridinoline/creatinine
      (PYR/CREA) by immunoassay. Histomorphometric results showed that PTH(1-34)
      progressively increased Cn.BV/TV but E2 failed to maintain them. Urinary PYR/CREA
      results showed that E2-treated groups had lower values. We conclude that E2 dose
      > 20 micrograms/kg/d is required to maintain the PTH mediated bone gain.

PMID- 8579936
TI  - Risedronate plus prostaglandin E2 is superior to prostaglandin E2 alone in
      maintaining the added bone after withdrawal in a non-growing bone site in
      ovariectomized rats.
AB  - Effects of risedronate and prostaglandin E2 (PGE2) alone or in combination on the
      distal tibia, a non-growing bone site with closed epiphysis at 3 months of age,
      were studied in ovariectomized (ovx) rats. Six-month-old Sprague-Dawley female
      rats were either ovx or sham-ovx. Rats were treated immediately after operation
      either with risedronate (5 micrograms/kg/2x/wk), PGE2 (6 mg/kg/d), or
      risedronate+PGE2 for 60 days (on-groups) and followed by 60 days without
      treatment (off-groups). Trabecular area, width and numbers were determined in
      metaphyseal cancellous bone of the distal tibia. No significant bone loss or
      structural changes were observed in the distal tibial metaphysis after 120 days
      of ovx. Risedronate alone did not produce any effect on bone mass during the
      treatment and the withdrawal periods. PGE2 alone increased the trabecular bone
      mass associated with thickened trabeculae and increased trabecular numbers.
      However, some of the newly formed bone was lost at the end of 60 days withdrawal.
      Combination of risedronate and PGE2 treatment added the same amount of bone mass
      as PGE2 alone, and the added new bone was maintained during the 60 days
      withdrawal. These results indicate that treatment with risedronate and PGE2 can
      preserve the anabolic effect of PGE2 on bone mass for at least 60 days after
      treatment.

PMID- 8579937
TI  - Assessing bone quality--animal models in preclinical osteoporosis research.
AB  - As new agents are developed for osteoporosis prevention and intervention, the
      need for reliable animal models becomes more pressing. At the same time, the
      necessity of not focusing on bone mass as the sole efficacy parameter has become
      apparent. Before accepting any agent for clinical osteoporosis trials, FDA now
      requires that it has proven its efficacy in a small animal model and also in a
      larger animal model with known intracortical bone remodeling. This efficacy
      should be proven both concerning bone mass and bone biomechanical competence. In
      this paper, methods for testing bone quality in small and large animal models are
      presented, and the necessity of testing several skeletal sites: vertebrae, long
      bones, and femoral necks is discussed.

PMID- 8579938
TI  - Perspectives of pQCT technology associated to biomechanical studies in skeletal
      research employing rat models.
AB  - Assessment of bone material quality and architectural indicators by means of
      peripheral quantitative computed tomography (pQCT) offers a wide perspective for
      skeletal research employing noninvasive procedures. Some mechanically-validated
      examples of these pQCT applications in animal models are described. They concern
      (a) the analysis of bone mechanostatical interrelationships as shown by
      experimental "distribution/quality" curves, and (b) the noninvasive determination
      of bone strength. An attractive attempt to extrapolate the latter to human bone
      studies is also discussed.

PMID- 8579940
TI  - Intravenous olpadronate restores ovariectomy-affected bone strength. A
      mechanical, densitometric and tomographic (pQCT) study.
AB  - Female Wistar rats aged 3 months were ovariectomized (OX, n = 27). Three months
      later they were given i.v. doses of 150 (6), 300 (7), or 600 (6) ug/kg 2/wk of
      olpadronate during 12 weeks or left as OX controls (OXc). Bending fracture load
      of femur diaphyses, reduced in OXc, was recovered by olpadronate. This effect was
      paralleled by changes in material quality indicators as DEXA-BMD, tomographic
      (volumetric) BMD, elastic modulus, and maximum elastic stress of cortical bone.
      No changes were induced by any of the treatments on cross-sectional area or
      moment of inertia. Diaphyseal stiffness, not reduced by OX, was enhanced to
      overnormal values by olpadronate at any dose. None of the treatments affected the
      normal mechanostatic interrelationships between cross-sectional architecture and
      bone material quality indicators. The positive effects described point out
      important differences in bisphosphonate action on bone biomechanics according to
      the experimental conditions assayed.

PMID- 8579939
TI  - Reduced concentrations of collagen cross-links are associated with reduced
      strength of bone.
AB  - The known cross-links of bone collagen are derived from lysine and hydroxylysine.
      The first step in the enzymatic cross-linking process is a deamination by lysyl
      oxidase producing an aldehyde which then may condense with a lysyl or
      hydroxylysyl residue of a neighbouring collagen molecule. Some of the resulting
      divalent aldimine and oxo-imine cross-links may later on be incorporated in
      trivalent hydroxylysyl-pyridinoline and lysyl-pyridinoline cross-links. In bone
      collagen prepared from the cancellous bone of vertebral bodies of osteoporotic
      individuals we found a reduced stability towards acetic acid and pepsin, and a
      substantial reduction in the concentration of the divalent collagen cross-links
      compared with sex- and age-matched controls. To what extent do the collagen cross
      links influence the mechanical properties of bone? beta-amino-propionitrile
      (BAPN) irreversibly inhibits the enzyme lysyl oxidase and therefore, the
      formation of cross-links between the collagen molecules. In the present study
      female rats, 70 days old, injected subcutaneously two times daily with BAPN (333
      mg/kg/day) for 1 month and saline injected control rats were studied. The
      concentration of the hydroxypyridinium cross-links of femoral mid-diaphyseal
      cortical bone was determined by HPLC with fluorescence detection and the
      mechanical properties of the rat femoral diaphyses were analyzed by a materials
      testing machine. The BAPN injections resulted in a 45% reduction in the
      concentration of the hydroxypyridinium cross-links and a 31% decrease in the
      stability of the bone collagen towards acetic acid and pepsin compared with the
      control rats. No changes were found in ash or collagen concentrations of the
      cortical bone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579941
TI  - Dual-energy X-ray absorptiometry in sheep: experiences with in vivo and ex vivo
      studies.
AB  - As different large animal models of osteopenia and osteoporosis are explored, the
      use of DXA to rapidly, non-invasively and accurately estimate BMD will become
      widespread. We used DXA in live sheep and cadaveric material and the areas of
      trabecular bone that are most accessible on a simple, repeatable basis in the
      sheep were the lumbar vertebrae (L4-L6/L5-L7), the CAL and the DR. We performed
      dual-energy X-ray absorptiometry (DXA) using an Hologic QDR 1000-W bone
      densitometer to measure bone mineral density (BMD) at various regions of interest
      in anesthetized sheep and cadaveric specimens of sheep. In vivo measurements of
      L4-L6/L5-L7, the calcaneus (CAL) and distal radius (DR) in 48 intact 3 to 5-year
      old ewes (same breed) were performed. Correlations between the different bones
      were investigated. In an in vivo precision study, BMD of L3-L6/L7, CAL and DR was
      determined with one animal repositioned between 10 scans of each bone. In another
      study, ex-vivo BMD measurements of the proximal and distal femur, proximal tibia,
      and proximal humerus were performed on isolated bones of 45 ewes of similar age.
      Excised vertebrae were scanned on the Hologic QDR 1000-W and on a Lunar DPX (at
      another site) and the data were compared. Correlations of BMD between individual
      vertebrae in anesthetized sheep were excellent (r = 0.944- 0.843; P < 0.0001).
      Correlation between BMD of individual vertebrae and CAL was good (r = 0.677
      0.630), while correlation between BMD of individual vertebrae and DR was also
      good (r = 0.551-0.507; P < .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579942
TI  - Skeletal changes in the ovariectomised ewe and subsequent response to treatment
      with 17 beta oestradiol.
AB  - The ewe has been suggested as a suitable large animal model for assessment of
      therapeutic agents for the treatment of osteoporosis. In this study we asses the
      response of ewe bone mineral parameters, using dual energy x ray absorptiometry
      (DXA), after ovariectomy. Regular DXA analysis was performed over a period of 75
      weeks followed by a period of dosing with 17 beta oestradiol. Total body bone
      mineral density (BMD) was reduced in ovariectomised animals 15 weeks post
      operatively. BMD remained lower than control animals for the entire pre dose
      period. Subsequently, dosing with 17 beta oestradiol prevented further loss of
      bone over a period of 38 weeks. Several complicating factors were noted during
      the study including seasonal BMD variation, a correlation between fat/lean ratio
      and total body BMD together with a reversible reduction in bone mineral content
      as a result of lactation. Also changes in BMD were associated with age at
      ovariectomy.

PMID- 8579943
TI  - Changes in bone mineral density and bone-specific alkaline phosphatase in
      ovariectomized ewes.
AB  - An animal model of human osteoporosis which adequately meets many of the criteria
      needed to test new therapeutic agents is currently unavailable. The old ewe may
      serve this purpose, as changes in bone remodeling occur within 3 months, and a
      difference in bone mass has been indicated 6 months after ovariectomy. In the
      current study, we have measured longitudinal changes in bone mass and bone
      specific alkaline phosphatase (BSAP) for six months in 7-9 year old
      ovariectomized (OVX) ewes. Thirty ewes were divided into three groups: sham
      treated (n = 9), OVX (n = 12) and OVX with estrogen implants (OVXE, n = 9). Bone
      mineral density (BMD) was determined at 0, 3 and 6 months in the vertebrae (L4
      L6/L5-L7), calcaneus (CAL) and distal radius (DR) using dual-energy X-ray
      absorptiometry (DEXA). Bone-Specific Alkaline Phosphatase (Tandem-R Ostase;
      Hybritech) was determined at monthly intervals. Body weight did not significantly
      change in any group during treatment compared to sham, although a trend of
      increasing body weight at 3 and 6 months was apparent in both OVX groups.
      Luteinizing hormone increased in all OVX ewes as a function of time as expected,
      demonstrating successful ovariectomies. Uterine weight was significantly
      increased (p < 0.01) in the OVXE animals compared to Sham and OVX groups. BMD did
      not change significantly during the 6-month treatment period in the CAL or DR.
      BMD in the vertebrae (L4-L6/L5-L7) was significantly lower in the OVX group
      compared to sham (p < 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579944
TI  - Development of osteopenia in ovariectomized cynomolgus monkeys (Macaca
      fascicularis).
AB  - Spinal osteopenia that is due in part to failure to gain bone has previously been
      reported in ovariectomized nonhuman primates. In these studies, development of
      osteopenia over one year was followed by dual-energy x-ray absorptiometry in both
      domestically-reared and feral ovariectomized (OVX) and sham-ovariectomized (SHAM)
      cynomolgus monkeys. To promote development of absolute osteopenia, the
      domestically-reared animals were all older than nine years and were fed a diet
      containing 0.14% calcium for most of the experimental period. Both SHAM and OVX
      feral animals fed 0.6% calcium gained bone mass, with significantly lower rates
      of gain in SHAM monkeys. OVX domestically-reared monkeys lost bone during one
      year, while SHAM domestically-reared animals showed no significant change from
      baseline. Thus, relative osteopenia developed in both experiments, but only the
      domestically-reared animals developed absolute osteopenia. Nonhuman primates are
      the only animal model shown to develop absolute osteopenia after ovariectomy.
      These data suggest that absolute osteopenia develops after ovariectomy in monkeys
      with stable pre-ovariectomy bone mass which are fed a level of calcium comparable
      to that consumed by American women.

PMID- 8579945
TI  - Comparison between bone density and bone strength in glucocorticoid-treated aged
      ewes.
AB  - In order to assess if bone densitometry could be used as an indicator to evaluate
      bone fragility in short term studies performed on glucocorticoid-treated ewes,
      correlations between DXA measurements and biomechanical parameters obtained on
      the same bones were established in 27 aged ewes including sixteen animals treated
      with methylprednisolone 15 mg/day for 4 months and eleven untreated animals. DXA
      measurements were performed ex-vivo on HOLOGIC QDR-1000+ device. Biomechanical
      testings included a three-point bending test on the femur and a compression test
      on cylinders of cancellous bone excised from two lumbar vertebrae selected
      between L6 and L4. At the femoral site, bone mineral density was correlated with
      the bending stiffness (r = 0.65) and the ultimate bending strength (r = 0.64)
      whereas, at the vertebral site, biomechanical parameters failed to correlate with
      bone mineral density assessed by DXA. This apparent lack of correlation between
      vertebral bone mass and trabecular bone strength is mainly linked to anatomical
      characteristics of the ewe: in this species, the vertebral posterior arches,
      which consist mainly of cortical bone, are very large compared to the vertebral
      body and strongly influence the bone mineral density evaluated on the intact
      vertebra. This is not the case with other large animals, for instance non-human
      primates. In conclusion, DXA can give a good evaluation of bone strength for ewe
      femurs, but results must be interpreted carefully at the vertebral site due to
      the anatomical characteristics of this animal species.

PMID- 8579946
TI  - Effect of treatment for 3 months with human parathyroid hormone 1-34 peptide in
      ovariectomized cynomolgus monkeys (Macaca fascicularis).
AB  - Clinical data suggest that PTH may increase cancellous bone mass at the expense
      of cortical bone in human beings. In this study, the effects of PTH on whole
      body, axial and appendicular bone mass were studied in an animal model with
      Haversian cortical bone remodelling. Ovariectomized, young adult, female
      cynomolgus monkeys were assigned to Placebo (n = 9) or PTH groups (n = 10). The
      PTH group received 10 micrograms/kg synthetic human PTH(1-34) peptide by SC
      injection, 3 days/week for 3 months and the Placebo group received vehicle.
      Spinal and whole body bone mass were measured by DXA, and proximal tibia, distal
      radius and mid-radius bone mass were measured by quantitative computed tomography
      (QCT) at baseline and 3 months. Small, transient increases in serum calcium were
      observed 4 hours after injection with PTH. Compared to placebo-treated animals,
      PTH-treated monkeys had no change in whole body bone mass, but a 5% increase in
      spinal bone mineral density. Cortical bone mass measured by QCT at appendicular
      sites was not affected by PTH treatment, but there were significant increases in
      cancellous bone mass in the proximal tibia, and a similar trend in distal radius.
      PTH stimulated dramatic bone gain in the lumbar spine and at appendicular
      trabecular bone sites during three months' treatment. There was no evidence of
      cortical bone loss during the same period.

PMID- 8579947
TI  - Dose-response effects of estradiol implants on bone mineral density in
      ovariectomized ewes.
AB  - In a longitudinal in vivo study, we studied the effect of two different doses of
      17 beta-estradiol (E2) administered in the form of a subcutaneous implant, on
      bone mineral density (BMD) of the lumbar vertebrae (L4, L5, L4-L6/L5-L7), the
      calcaneus (CAL) and the distal radius (DR) in ovariectomized (OVX) ewes. The BMD
      of various regions of the femur, tibia and humerus were studied at autopsy.
      Skeletally mature ewes (n = 45) were divided into four groups: sham operated (n =
      12), OVX (n = 15), OVX plus one E2 implant (OVXE, n = 12) and OVX plus two E2
      implants (OVX2E, n = 6). BMD of L4, L5, L4-L6/L5-L7, CAL and DR was determined at
      0, 6 and 12 months using dual-energy X-ray absorptiometry. In-vivo precision of
      BMD for the last three lumbar vertebrae ranged from 1.4-4.3%, and 1.5% and 3.5%
      for CAL and DR respectively. In the in vivo study, there were no significant
      changes in the mean BMD in the sham group at any time point (each group served as
      its own control). In the OVX group, mean BMD was significantly lower at L5 and DR
      at 6 months and significantly lower at L4 at 12 months. In the OVXE group, the
      mean BMD was significantly higher at L5, CAL and DR at 12 months. In the OVX2E
      group, BMD was significantly higher at CAL but significantly lower at L4 at 12
      months. None of the treatments produced significant changes of mean BMD of L4
      L6/L5-L7 at any time point.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8579948
TI  - Postparturient hypocalcemia of dairy cows: a model for the study of the
      interdependence of Ca, Pi, and Mg homeostasis.
AB  - Disorders of calcium, phosphorus and magnesium homeostasis in ruminants provide
      natural models for the study of the physiology and pathophysiology of these
      minerals. The knowledge that can be acquired with a better understanding of the
      pathogenesis of these diseases could give useful clues in the puzzle of human
      osteoporosis. In the present study, the case of parturient paresis of dairy cows
      is reexamined with a newly developed technique for the measurements of serum
      ionized magnesium concentrations (Mg2+). The concentrations of total magnesium
      (Mgtot), ionized calcium (Ca2+), total calcium (Catot), and inorganic phosphate
      (Pi) were also determined in the sera of seventeen 3- to 16-year-old Brown Swiss
      and crossed Simmental/Red Holstein cows during the periparturient period. In each
      animal, a transient increase of Mg2+ and Mgtot serum concentrations was observed
      in association with the transient decrease after parturition of Ca2+, Catot and
      Pi serum concentrations. On average, throughout the study, serum Mg2+
      concentrations were 68.5% of those of Mgtot whereas serum Ca2+ concentrations
      were 52% of those of Catot. The possible mechanisms involved in the transient
      increase of Mg2+ and Mgtot serum concentrations are discussed and the relevance
      of this data for osteoporosis is outlined.

PMID- 8579949
TI  - Postablation bone marrow regeneration: an in vivo model to study differential
      regulation of bone formation and resorption.
AB  - The postablation bone marrow regeneration model is an in vivo paradigm of
      synchronous bone formation and resorption restricted to a defined reference
      anatomical location. The blood clot that fills the medullary cavity immediately
      after marrow removal is organized by replacement with primary cancellous bone. At
      the peak of the osteogenic phase almost the entire medullary cavity is filled
      with the trabecular mesh. The primary bone trabeculae are then subjected to
      osteoclastic resorption and replacement by intact marrow. Since in animals of
      defined strain, sex and age the timing and extent of formation and resorption are
      highly reproducible, the postablation model in combination with simple vital
      methods and/or bone histomorphometry as well as molecular and biochemical
      approaches applied at specified time periods provides an efficient in vivo tool
      to assess the efficacy of antiresorptive agents as well as their possible adverse
      effects on bone formation. When applied to transgenic animals this model may
      become useful to determine the role of individual genes in matrix formation,
      mineralization and resorption.

PMID- 8579950
TI  - Transforming growth factor beta 1 stimulates bone formation and resorption in an
      in-vivo model in rabbits.
AB  - The influence of TGF beta 1 on bone was studied in a titanium device implanted
      into the tibia of rabbits. TGF beta 1 was infused via an Alzet osmotic pump
      calibrated to deliver at a rated of 200ng daily for 2 weeks before replacement. A
      hollow channel is incorporated into the device into which tissue can grow, and
      the histological sequence of events was observed over 6 weeks. In control
      samples, the rod-shaped piece of tissue at 2W consisted of spindle-shaped cells
      in the center, flanked at both ends by islands of trabecular bone lined by
      cuboidal osteoblasts and osteoclasts. By 4W, ingrowth of bone reached the center
      if the specimen, by which time, the bone surfaces were apposed by a single layer
      of flattened osteoblasts. However, osteoclastic resorption continued unabated so
      that by 6W, only a thin layer of cortical bone remained, enclosing a marrow
      cavity with hemopoietic elements. Significant differences were observed in
      samples continuously infused with TGF beta 1. At 2W, trabecular bone had reached
      further towards the center of the specimen and the granulation tissue was made up
      of cells that were more plump and cuboidal compared to the spindle cells of
      control sample. At 3W, there was increased bone volume and osteoid seams were
      thicker, covering a greater extent of the trabeculae surfaces. At 4W, the bony
      trabeculae were up to 3 times thicker than control trabeculae. There was very
      active bone resorption with many multinucleate osteoclasts and multilayered
      aggregates of cuboidal osteoblasts lining bony surfaces. Yet at 6W, the
      morphological appearance was similar to control samples.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8579951
TI  - The food-induced stimulation of bone resorption in the rat, assessed by the
      urinary [3H]-tetracycline excretion, is mediated by parathyroid hormone.
AB  - Using the urinary excretion of [3H]-tetracycline from prelabeled rats to monitor
      bone resorption, we have previously shown that food intake is associated with a
      rapid and large increase in bone resorption. This increase is blunted when the
      daily intake is fractionated into 4 portions instead of being given at once. Food
      fractionation also leads to a large increase in bone mass. In order to establish
      whether the thyroparathyroid gland is involved in this effect,
      thyroparathyroidectomized (TPTX) rats were studied. The food-induced increase in
      bone resorption was absent in TPTX rats. Therefore, the pattern of parathyroid
      hormone (PTH) was investigated during the development of the food-induced bone
      resorption, and under food fractionation. Rats were trained to eat their daily
      high Ca food in less than two hours. Thereafter they were given food portions of
      5 or 20 grams, respectively. PTH in serum was measured at 0, 1, 2, 3, and 4 hours
      after food intake. In rats given the large food portions, a conspicuous increase
      of PTH was found. In contrast, serum PTH of rats fed the small food portion did
      only change to an insignificant extent. This study in rats shows that the
      ingestion of a large meal induces a transient increase of PTH. The present
      results can therefore explain the formerly observed acute increase in bone
      resorption following food intake and its blunting by food fractionation. It is
      not known, whether such a mechanism occurs also in humans. If so, these results
      would provide the rational basis to decrease bone resorption by food
      fractionation.

PMID- 8579952
TI  - Measurement of bone resorption by strontium excretion in prelabelled rats.
AB  - The body handles strontium (Sr) in a similar way to calcium (Ca) in that Sr is
      absorbed by the gut, concentrated in bone and excreted in urine and feces. In
      this study, rats were labelled with Sr during growth and later subjected to
      various treatments affecting bone resorption and Sr excretion was measured during
      and after treatment. Six weeks old Wistar rats were repeatedly s.c. injected with
      SrCl2. After a period of 2 weeks after the last Sr injection the rats were
      subjected to various treatments. Sr clearance was then measured weekly for 2
      weeks. In the first experiment, the Sr labelled rats were sham-operated (sham) or
      ovariectomized (ovx) and urine collected afterwards. Sham rats were either
      treated with 4 daily s.c. clodronat injections at the beginning of the urine
      sampling, fed a low Ca diet (0.08% Ca) during the second sampling week or
      injected with saline. Urinary Sr excretion was decreased in the clodronate group
      during the first sampling week and increased in the Ca depleted group during
      feeding the low Ca diet. Sr excretion by ovx rats was similar to the sham
      control. In the second experiment, the effect of high-dose treatment with 24,25
      dihydroxyvitamin D3 (24,25(OH)2D3) or clodronate on bone resorption induced by Ca
      depletion was assessed by Sr output in urine and feces. Sr labelled rats were fed
      a low Ca diet and daily injected with 24,25(OH)2D3 or clodronate for 14
      consecutive days. Clodronate significantly decreased Sr output during both
      sampling weeks. Treatment with 24,25(OH)2D3 resulted in an increased Sr output
      indicating an increase in bone resorption.

PMID- 8579953
TI  - Canine bone marrow cell cultures infected with canine distemper virus: an in
      vitro model of Paget's disease.
AB  - We have previously shown that the canine paramyxovirus, canine distemper virus
      (CDV), is a possible aetiologic agent in Paget's disease of bone and in the
      canine bone disorder, metaphyseal osteopathy. More recently, we have examined the
      effects of CDV on the formation of multinucleated, tartrate resistant acid
      phosphatase positive, calcitonin receptor positive, osteoclast-like cells in
      cultures of canine bone marrow mononuclear cells, and shown that both in vitro
      and in vivo infection with CDV produced a dose dependent increase in the number
      and size of osteoclast-like cells. We have now extended these results to show
      that CDV infection induces interleukin-6 and c-Fos mRNA in these cells, similar
      to our recent findings in pagetic bone cells. These results further support the
      hypothesis that CDV might be involved in the aetiopathogenesis of Paget's disease
      and metaphyseal osteopathy and suggest that canine marrow culture systems will
      prove useful as an in vitro model to examine the disease processes in more
      detail.

PMID- 8579954
TI  - The heterogeneity of the osteopetroses reflects the diversity of cellular
      influences during skeletal development.
AB  - Experimental studies of the mammalian osteopetroses, characterized by generalized
      skeletal sclerosis, have illuminated a variety of mechanisms by which bone
      resorption can be reduced. We review recent data implicating a diverse group of
      growth factors, proto-oncogenes, and immune regulators that can influence
      skeletal development and account for the heterogeneity of the osteopetroses.
      Furthermore, similar studies are likely to continue to provide for improved
      clinical management of both osteopetrotic children and the localized and
      generalized osteopenias.

PMID- 8579955
TI  - Short treatment of osteoclasts in bone marrow culture with calcitonin causes
      prolonged suppression of calcitonin receptor mRNA.
AB  - Cells exhibiting osteoclast characteristics of calcitonin receptors (CTRs) and
      tartrate-resistant acid phosphatase (TRAP) histochemistry are formed in murine
      bone marrow cultures treated with 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3].
      We have previously demonstrated that CTR mRNA is highly expressed in these
      cultures. The aim of this study was to investigate homologous regulation of the
      CTR, and regulation of TRAP expression in osteoclast-like cells after brief
      treatment with salmon CT (sCT). Murine bone marrow cells were cultured in 9 cm
      dishes in the presence of 10 nmol/L 1,25-(OH)2D3. On day 6 of culture, when
      multinucleated cells were abundant, the cells were treated with 1 nmol/L sCT for
      1 h. Both control and treated cells were then harvested at intervals up to 72 h
      posttreatment, and both CTR and TRAP mRNA levels assessed by reverse
      transcription PCR (RT-PCR). In parallel cultures, cells with CTR expression
      detectable by autoradiography, and TRAP positivity by histochemistry, were
      counted. The effects of brief sCT treatment could be seen 6 h after treatment
      when the CTR RT-PCR product was markedly reduced. Total recovery of CTR mRNA
      levels had not occurred even after 72 h. Calcitonin treatment had little effect
      on TRAP mRNA levels. There was no difference in the numbers of multinucleated
      TRAP(+) osteoclast-like cells between treated and control cells. These results
      indicate that brief sCT treatment, while not influencing multinucleated
      osteoclast-like cell number, causes specific, acute reduction of CTR mRNA in bone
      marrow culture-derived osteoclasts. The prolonged decrease in CTR mRNA levels
      suggests that recovery may require new osteoclast formation, and indicates that
      regulation of the CTR in cells of the osteoclast lineage is different from that
      in nonosteoclastic cells and tissues.

PMID- 8579956
TI  - Histomorphometric and biochemical characterization of bone following acute severe
      burns in children.
AB  - Severe burns in adults is associated with an uncoupling of normal remodeling, low
      bone formation without reduced resorption. The risk of osteopenia that may occur
      under such circumstances is heightened by our detection in a cross-sectional
      study of low bone mass in severely burned children. We report here the acute
      histomorphometric and biochemical response of bone to severe burn injury, as well
      as bone mass in severely burned children. We enrolled 24 patients ages 5.8 to
      17.5 years following burns of 63 +/- 16% (SD) body surface area. Serum and urine
      were collected weekly until iliac crest bone biopsy was obtained 26 +/- 10 days
      postburn. Seventeen of 18 patients, including 5 patients receiving growth hormone
      treatment to accelerate wound healing, failed to take up doxycycline in
      trabecular bone, and had no detectable osteoblasts at the osteoid seam, while
      eroded surface was normal and osteoblasts were documented by staining. Thus, bone
      formation was virtually absent. There was an eightfold elevation in urinary free
      cortisol excretion and high serum levels of acute phase reactants and interleukin
      1 beta and -6. Biochemical markers of bone formation, osteocalcin, and type I
      procollagen propeptide were low, as were resorptive markers urinary pyridinoline
      and deoxypyridinoline. However, there was no correlation with resorptive surface.
      Mean age-related z-score for bone mass was -1.06 +/- 1.05, 40 days postburn.
      Immobilization and endogenous corticosteroid production may be the main factors
      responsible for acutely reduced bone formation while inflammatory cytokines may
      mediate resorption.

PMID- 8579957
TI  - Intermittent compression stimulates cartilage mineralization.
AB  - The effects of intermittent hydrostatic compressive force (ICF; 13 kPa applied at
      0.3 Hz frequency), as a substitute for moderate loading in vivo, on ossifying
      bone organ cultures, were evaluated by means of (histo)-morphometry. In earlier
      studies, biochemical tests have shown an increased 45Ca intake and an increased
      alkaline phosphatase activity in bone organ cultures that received ICF,
      suggesting that ICF promoted matrix mineralization. The purpose of this study was
      to examine whether an effect of ICF on mineralization can be described by means
      of histomorphometrical analysis. Fetal mouse metatarsal bone rudiments were
      cultured for 5 days in serum-free medium, with (experimental) or without
      (control) ICF. Linear measurements taken during culture demonstrated that the
      dark zone in the center of the rudiment, representing mineralized hypertrophic
      cartilage, became significantly longer in the group that received ICF when
      compared with the control group. This finding was in conformation with the former
      studies. Histological sections of the rudiments, stained with Goldner's trichrome
      method were used to study changes at the cellular level and to describe the
      position and relative amount of mineralizing cartilage matrix (defined as Goldner
      positive matrix [GPM]). Histomorphometry demonstrated that ICF treatment
      significantly increased the length of the hypertrophic cartilaginous zone and
      enhanced the amount of GPM between the mineralizing hypertrophic chondrocytes.
      However, the total length of the zone containing GPM was not increased, nor was
      the future bone collar, consisting of a thin osteoid seam, lengthened by ICF.
      These data indicate that the cellular processes involved in chrondrocyte
      hypertrophy were accelerated by ICF, as well as the extracellular processes
      leading to matrix mineralization. The study supports the earlier conclusion that
      embryonic bone rudiments are sensitive to mechanical stimulation and that
      moderate loading promotes their ossification in vitro.

PMID- 8579958
TI  - Regulation of plasma osteocalcin by corticosterone and norepinephrine during
      restraint stress.
AB  - Osteocalcin (OC), an extracellular calcium-binding protein of bone origin, is
      synthesized by osteoblasts and binds with high specificity to bone mineral
      crystals. A small, but relatively consistent portion of newly synthesized OC
      which is released to circulation has been well correlated with histological
      indices of osteoblastic activity. Synthesis of OC is regulated by numerous
      hormones including glucocorticoids. We previously reported that mild mental
      stressors such as cage change or cold exposure decreased rat plasma OC by up to
      40% within 1 h. A similar response was induced in a time- and dose-related manner
      by injection of physiological levels of corticosterone (CS), the active
      glucocorticoid in rats. Prone immobilization by foot restraint of conscious rats
      for up to 2 h (IMMO) is a well-characterized model of classic "fight-or-flight"
      response. This model induces an immediate and prolonged elevation of CS, as well
      as the catecholamines epinephrine (E) and norepinephrine (NE). In marked contrast
      to milder stressors, immobilization induced an immediate increase of plasma OC,
      greater than 50% within 5-20 min, which returned toward normal after 2 h of
      restraint. Selective ablation of the hormones by adrenal medulectomy,
      adrenalectomy, or blockade of sympathetic ganglia did not abolish the initial
      rapid rise of plasma OC. Even before IMMO, plasma OC was increased by about 50%
      in the absence of sympathetic neural function or adrenal CS production. The
      presence of both CS and NE, but not E, was required to return plasma OC
      concentrations to basal levels. This strongly suggests interaction of CS and NE
      to regulate plasma OC and its release from bone. As expected, prior cold exposure
      lowered plasma OC, but did not abolish a subsequent increase in response to IMMO,
      nor did IMMO repeated daily for 7 days. The stimulus for the initial rapid
      elevation of OC is unknown, but likely to be of importance in the role OC plays
      in response to stress. Further investigation of the OC under mental stress should
      help to understand the function of this abundant and highly conserved bone
      protein.

PMID- 8579959
TI  - Effects of zinc and divalent cation chelators on ATP hydrolysis and Ca deposition
      by rachitic rat matrix vesicles.
AB  - Elsewhere it has been shown that zinc is highly concentrated in the hypertrophic
      zone of epiphyseal cartilage. It has also been shown that zinc deficiency can
      result in abnormal bone development, suggesting a direct or indirect role for
      zinc in calcification. Because matrix vesicles have been implicated in the
      initiation of calcification, we tested the effect of zinc and its chelators, such
      as EGTA and phenanthroline, on ATP-dependent Ca uptake by rat matrix vesicles.
      EGTA pretreatment of matrix vesicles inhibited ATP-dependent Ca uptake by 50%. To
      see if zinc depletion by EGTA pretreatment is responsible for decreased levels of
      ATP-dependent Ca uptake, ZnCl2 concentrations, ranging from 5 to 100 mumol/L,
      were tested for their ability to restore Ca deposition. Zinc exerted a striking
      enhancing effect on ATP-dependent Ca uptake of both untreated and EGTA-pretreated
      matrix vesicles in a dose-dependent manner. A 50% activation occurs at about 16
      mumol/L Zn2+. At 63 mumol/L Zn2+, there was a fourfold increase in Ca-depositing
      activity. Addition of an excess amount of phenanthroline relative to Zn2+
      concentration to the reaction mixture failed to abolish activation of Ca uptake
      by Zn2+, indicating that the putative chelator-Zn2+ complex formation did not
      prevent activation. The observed partial inhibition of ATPase and the activation
      of ATP-dependent Ca uptake of Zn2+ suggest that, in addition to ATPase, some
      other Ca and/or Pi uptake activators responsive to Zn2+ treatment are present in
      mammalian matrix vesicles.

PMID- 8579960
TI  - In vivo, human parathyroid hormone fragment (hPTH 1-34) transiently stimulates
      immediate early response gene expression, but not proliferation, in trabecular
      bone cells of young rats.
AB  - Intermittent PTH increases trabecular bone mass in vivo by stimulating osteoblast
      differentiation to increase bone formation. The molecular events that mediate the
      anabolic effect of PTH on osteoblasts have not been characterized. We
      investigated if PTH regulated mRNA expression of proto-oncogenes, c-fos, c-jun,
      and c-myc, early response genes that have been shown to be involved in the
      regulation of both cell proliferation and differentiation. As PTH also regulates
      the early expression of the cytokine, interleukin-6 (IL-6), in bone cells in
      vitro, we also investigated if this occurred in vivo, in concert with the other
      early response genes. Northern blot hybridization was used to analyze mRNA
      expression in the metaphysis of the distal femur of young rats. To determine the
      proliferative state in these femurs, mRNA expression of the cell proliferation
      marker histone, H4, was assessed. Subcutaneous administration of a single
      injection of human PTH (1-34) at 8 micrograms/100 g, a dose known to increase
      bone forming surfaces, induced rapid and transient expression of c-fos, c-jun, c
      myc, and IL-6 mRNA. A second novel transcript for IL-6 was detected, but its
      significance remains unknown. Induction of all these messages was evident by 1 h;
      the levels of mRNA returned to baseline after 3-6 h. Concurrently, PTH had a
      small inhibitory effect on the expression of histone H4 mRNA. We conclude that,
      in vivo, PTH upregulates cell differentiation in trabecular bone by transient
      stimulation of the early response genes and IL-6, while downregulating cell
      proliferation.

PMID- 8579961
TI  - Bone changes in mucopolysaccharidosis VI in cats and the effects of bone marrow
      transplantation: mechanical testing of long bones.
AB  - Mucopolysaccharidosis VI (MPS VI) is a genetic lysosomal storage disease in which
      a defect in aryl sulfatase B leads to accumulation of the glycosaminoglycan
      dermatan sulfate and abnormalities in the development of cartilage and bone. A
      feline model of this disease was used to evaluate the efficacy of bone marrow
      transplant (BMT) therapy. Long bones from MPS VI cats (N = 6) and MPS VI + BMT
      cats (N = 7) were compared with control cats (N = 11) and control + BMT cats (N =
      5) in mechanical tests. Dissected femurs and tibias were subjected to three-point
      bending and a subgroup of tibias were tested with the mechanical response tissue
      analyzer (MRTA) in which vibration is used to measure tissue impedance. Cats with
      MPS VI had markedly decreased stiffness and strength in both bone (p < 0.01).
      There was no significant difference in the MPS VI + BMT group. In the tibias,
      there was also decreased stiffness and strength in the control + BMT group as
      compared to controls (p < 0.05). However, when cross-sectional area was used to
      normalize for bone size there was good correlation with strength in both femurs
      (r = 0.907, p < 0.01) and tibias (r = 0.915, p < 0.1), and there were no
      significant differences between groups in the modulus of elasticity. In the
      tibias, in which stiffness was measured by MRTA, there was significant
      correlation with three-point bending stiffness. These results indicate that, in
      cats with MPS VI, the decreases in stiffness and strength of long bones can be
      largely accounted for by the decrease in bone size (osteopenia) that is present.

PMID- 8579963
TI  - Myositis and myopathies.

PMID- 8579964
TI  - Raynaud's phenomenon, scleroderma, overlap syndromes, and other fibrosing
      syndromes.

PMID- 8579962
TI  - Effects of droloxifene on prevention of cancellous bone loss and bone turnover in
      the axial skeleton of aged, ovariectomized rats.
AB  - The purpose of this study was to determine the efficacy of droloxifene (DRO), an
      estrogen antagonist/agonist, in preventing ovariectomy (OVX)-induced lumbar
      vertebral cancellous bone loss and bone turnover in aged female rats. Fifty-three
      Sprague-Dawley female rats were OVX or sham-operated at 19 months of age, and
      divided into 6 groups: (I) sham-operated controls; (II) OVX vehicle controls;
      (III) OVX rats treated with E2 at 30 micrograms/kg/day; (IV)-(VI) OVX rats
      treated with DRO at either 2.5, 5, or 10 mg/kg p.o. daily. The treatment period
      was 8 weeks. Static and dynamic cancellous bone histomorphometric parameters were
      determined on 4 and 10 microns thick, undecalcified, double-fluorescent labeled
      sections of the fourth lumbar vertebral body. Changes in body weight, uterine
      weight, and total serum cholesterol were also determined. OVX for 8 weeks in 19
      month-old female rats resulted in reduced trabecular bone volume (-18%) and
      trabecular width (-10%) and increased labeling perimeter (+52%), bone formation
      rate/bone surface referent (+60%), bone formation rate/bone volume referent
      (+77%), osteoclast number (+41%), and osteoclast perimeter (+41%). E2 treatment
      at 30 micrograms/kg/day for 8 weeks prevented OVX-induced cancellous bone loss
      and decreased bone resorption, bone formation, and bone turnover to the values of
      sham controls. DRO at 2.5-10 mg/kg/day completely prevented bone loss and bone
      turnover associated with estrogen deficiency. Osteoclast number and perimeter
      were significantly decreased in DRO-treated-OVX rats compared to both sham and
      OVX controls. Trabecular bone volume, trabecular width, labeling perimeter, bone
      formation rate/bone surface referent, and bone formation rate/bone volume
      referent showed no differences in DRO-treated OVX rats compared to those of E2
      treated OVX rats and sham controls. These histomorphometric results indicated
      that DRO is an estrogen agonist on cancellous bone of lumbar vertebral bodies of
      aged, OVX rats. Further, E2 treatment prevented the OVX-induced increase in body
      weight gain and nonsignificantly reduced total serum cholesterol compared to OVX
      controls. Body weight gain and total serum cholesterol did not differ between OVX
      rats treated with E2 and sham controls. In OVX rats treated with DRO, body weight
      decreased significantly in a dose-response manner, and total serum cholesterol
      was significantly reduced by 65% to 70% compared to both sham and OVX controls.
      In addition, treatment with E2 increased uterine weight to the value of sham
      controls in OVX rats. However, DRO had no effect on uterine weight at either 2.5
      or 10 mg/kg/day, while it only slightly but significantly increased uterine
      weight over OVX controls at 5 mg/kg/day. We conclude that DRO was efficacious in
      the prevention of lumbar vertebral cancellous bone loss and in the decline of
      total serum cholesterol but had no effect on uterine weight in the aged, OVX
      female rats. Our data suggest that DRO is a potentially useful agent for the
      prevention of vertebral bone loss leading to spinal fractures in postmenopausal
      women.

PMID- 8579965
TI  - Muscle biopsy.
AB  - Muscle biopsy remains a critical component in the evaluation of myopathies.
      Recent literature demonstrates that percutaneous biopsy instruments can
      effectively procure muscle tissue for analysis in clinical and research settings.
      We review issues of muscle biopsy technique and specimen processing in the
      context of available clinical methods for tissue analysis. A survey of recent
      literature illustrates contributions made by the histologic, histochemical, and
      ultrastructural aspects of muscle analysis to our understanding of the
      pathophysiologic mechanisms and clinical manifestations of selected inflammatory,
      mitochondrial, and infectious myopathies.

PMID- 8579966
TI  - Enzyme and muscle diseases.
AB  - Two distinct areas of development contribute to the importance of enzymology in
      skeletal muscle disease: the measurement of enzymes in serum as a diagnostic aid
      and the investigation of enzyme deficiencies as the cause of metabolic myopathy.
      Currently, serum enzyme measurement, particularly creatine kinase, is used to aid
      in the detection of suspected myopathy, to differentiate myopathy from neurogenic
      disease, to identify dystrophies at a preclinical stage, to detect female
      carriers of dystrophies, and to assess response to therapy. Metabolic myopathies
      are disorders of muscle energy production that result in skeletal muscle
      dysfunction. The biochemical basis of such disorders is often a specific single
      enzyme defect. The tremendous advances in the molecular genetics of such
      disorders has added remarkably to our understanding of the primary defects
      involved and possible heterogeneity displayed at the molecular level.

PMID- 8579967
TI  - Dystrophinopathies and related disorders.
AB  - Muscular dystrophies primarily affect skeletal muscle and are characterized by
      progressive muscle wasting and weakness. Although these diseases have been
      clinically recognized for some time, genetic defects in a number of muscular
      dystrophies only recently have been identified. One of the most important
      advances in understanding the molecular genetics of neuromuscular diseases has
      been the cloning of the gene encoding dystrophin, the protein that is absent in
      the muscle of patients with Duchenne and Becker muscular dystrophy. Several
      dystrophin-associated proteins have been identified. Components of the dystrophin
      glycoprotein complex are being characterized, and evidence indicates that
      proteins of this complex may be responsible for other forms of muscular
      dystrophy.

PMID- 8579968
TI  - New advances in the understanding of sporadic inclusion-body myositis and
      hereditary inclusion-body myopathies.
AB  - This review emphasizes new advances in seeking the pathogenic mechanisms of
      sporadic inclusion-body myositis and hereditary inclusion-body myopathy
      syndromes. Clinical and pathologic similarities and differences between sporadic
      and hereditary forms are described. Hypotheses are presented regarding the
      possible causes and consequences of abnormally accumulated intramyofiber beta
      amyloid precursor protein (beta APP) (including beta-amyloid protein and C- and N
      terminal epitopes), hyperphosphorylated tau, alpha 1-antichymotrypsin,
      apolipoprotein E, prion protein, ubiquitin, nicotinic acetylcholine receptor and
      its 43-kD associated protein, fibroblast growth factor, and transforming growth
      factor-beta. Also increased are beta APP mRNA and prion protein mRNA. Striking
      similarities between the pathology of muscle specimens from sporadic inclusion
      body myositis and samples from the brains of patients with Alzheimer's disease in
      regard to Congo red positivity and accumulations of several proteins are
      discussed. Because most of the proteins that pathologically accumulate throughout
      the abnormal muscle fibers also accumulate focally at normal human neuromuscular
      junctions, the possible "junctionalization" of nonjunctional nuclei as a
      pathogenic mechanism in the muscle fiber is discussed.

PMID- 8579969
TI  - Myopathy and HIV infection.
AB  - Skeletal muscle involvement may occur at all stages of HIV infection. The most
      simple classification of muscular disorders in HIV-infected patients is 1) HIV
      associated myopathies, 2) zidovudine myopathy, 3) HIV wasting syndrome, and 4)
      opportunistic infections and tumoral infiltrations of muscle. Immunohistology for
      major histocompatibility complex class I antigen and histochemical reaction for
      cytochrome c oxidase are helpful in correctly classifying a myopathy as HIV
      polymyositis or zidovudine myopathy. Studies of cytokine expression in HIV
      infected patients and of supplementation with compounds such as carnitine or
      micronutrients such as selenium might yield new insights into the pathogenesis
      and treatment of the various AIDS-associated muscular disorders.

PMID- 8579970
TI  - T cell-mediated immune mechanisms in myositis.
AB  - Advances in molecular biologic techniques and the availability of novel
      immunologic reagents have allowed new approaches to understanding the
      pathogenesis of human autoimmune diseases, including the idiopathic inflammatory
      myopathies. Indirect evidence that autoreactive T cells mediate muscle
      inflammation in the human myositis syndromes has been strengthened by recent
      studies describing restricted T cell receptor gene expression in certain clinical
      and/or serologic groups of myositis patients. These findings are supported by
      other investigations documenting abnormal patterns of cytokine, adhesion
      molecule, and major histocompatibility complex antigen expression within
      inflammatory lesions. The major challenge of future studies is to identify the
      specific antigen(s) responsible for initiating and perpetuating these harmful
      immune responses.

PMID- 8579971
TI  - Treatment of inflammatory myopathy with intravenous gamma globulin.
AB  - Intravenous immunoglobulin (IVIg) is a new modality used to help treat conditions
      associated with immune dysregulation. The inflammatory myopathies are a group of
      complex diseases including dermatomyositis, polymyositis, and inclusion-body
      myositis. Overall evaluation of IVIg in myopathy has been hampered by difficulty
      in accurately diagnosing and assessing disease activity. The lack of large, well
      controlled, double-blind trials has precluded clear evaluation of the
      effectiveness of IVIg in these diseases. However, from the data presented in
      published reports, it appears that IVIg may be useful in the treatment of
      inflammatory myopathies, particularly dermatomyositis.

PMID- 8579972
TI  - Measuring disease activity and severity in scleroderma.
AB  - Now that guidelines for conducting trials of disease-modifying treatments in
      systemic sclerosis (SSc) have been published and guidelines for evaluating SSc
      organ-specific treatments are in preparation, our attention should focus on how
      to measure disease activity and severity in SSc. Several proposals for measuring
      disease severity have been forwarded and are discussed. In this editorial, what
      we know of SSc natural history and pathophysiology is reviewed, and several
      candidate variables that may reflect disease activity are proposed for evaluation
      in longitudinal studies and/or drug trials.

PMID- 8579973
TI  - Molecular genetics of systemic sclerosis.
AB  - The results of most recent studies suggest that systemic sclerosis (SSc) is a
      composite disease of major histocompatibility complex (MHC)-associated
      autoantibody responses, which have specific clinical correlates. Both the
      anticentromere and anti-topoisomerase I (anti-topo I) antibody responses have
      been linked to HLA-DQB1 alleles, although recent data suggest that certain HLA
      DRB1 alleles are important for the anti-topo I response and that HLA-DPB1 alleles
      also may have a role. Antibodies to the nucleolar specificity PM-Scl have
      consistently been linked to the HLA-DRB1*0301, DQA1*0501, and DQB1*0201
      haplotypes. Antibodies against fibrillarin, another nucleolar specificity, have
      been linked to certain HLA-DQB1*06 alleles. With the establishment of animal
      models of SSc, recent attention has been drawn to other genes that may be
      involved in the pathogenesis of this disease. To date, however, none have been
      found in humans, although comprehensive studies of this type are lacking. One
      particularly attractive area for study is the fibrillin loci on chromosome 15,
      syntenic to the region on mouse chromosome 2 to which the tsk gene has been
      mapped. Other locations include the interleukin-1 alpha and interleukin-beta
      genes (or their promoters) or oncogenes. These areas should provide potentially
      fruitful areas of investigation in the near future.

PMID- 8579974
TI  - Raynaud's phenomenon and the vascular disease in scleroderma.
AB  - Raynaud's phenomenon (RP) is the most common feature of vascular disease in
      scleroderma. The diagnostic methods and mechanisms involved in the development of
      RP continue to be defined, and deficiency in the endothelial-dependent
      vasodilatory mechanism is suggested. Neuronal involvement in the pathogenesis of
      vasospasm is illustrated by a defective neuromediated vasodilatory mechanism in
      both spontaneous RP and vibration white-finger syndrome. The exact neuronal
      related mechanism(s) is not known, but the development of scleroderma-like dermal
      changes following spinal cord injury suggests an important role for neuronal
      participation in the development of scleroderma. Mechanisms involved in
      endothelial injury are still not known, but the complement system may be
      involved, as suggested by the finding of decreased endothelial expression of the
      complement protective molecular system in scleroderma. Occurrence of vasculitis
      in the digital arteries in patients with digital ischemic lesions suggests that
      immune-mediated vascular injury occurs in the disease. The role of
      antiendothelial antibodies is questioned in view of the lack of endothelial
      specificity for the antibodies, but the association of anticentromere antibodies
      with vascular occlusion was confirmed. Therapeutic interventions stressing an
      individualized approach are recommended. Spinal cord stimulation and continued
      iloprost infusion are some of the newer proposed therapies for patients with
      difficult vascular complications.

PMID- 8579975
TI  - Connective tissue metabolism including cytokines in scleroderma.
AB  - Review of the currently published literature on systemic sclerosis emphasizes the
      role of adhesion molecules, growth factors, immune reactions, and aberrant
      fibroblast biology and metabolism in effecting vascular and connective tissue
      alterations in this disease and its variants.

PMID- 8579976
TI  - Immunologic aspects of scleroderma.
AB  - Activation of both cellular and humoral immunity are early events in systemic
      sclerosis (SSc) that appear to contribute to disease pathogenesis. Recent reports
      suggest that CD4+ and CD8+ T cells and a subset of gamma delta T cells each may
      play a role in the disease. Interest in potential profibrotic effects of
      transforming growth factor-beta in SSc continues. Expression of a variety of
      adhesion molecules is increased on fibroblasts and endothelial cells in SSc
      patients, as are circulating levels of the same molecules. Different autoantibody
      specificities are generated in B cells from tight-skin mice by use of identical
      VH genes, with similar V kappa genes but different J kappa segments. Centromeric
      proteins, topoisomerase I, RNA polymerases I, II, and III, fibrillarin, and
      upstream binding factor may become autoantibody targets in SSc because they are
      presented to the immune system as part of larger multiunit complexes. Homology
      between target autoantigens and infectious agents suggests that molecular mimicry
      initiates some autoantibody responses in SSc patients. Genetic factors influence
      the pattern of autoantibodies produced in different populations. Exogenous agents
      can induce autoantibodies in humans and mice that are similar to those seen in
      spontaneous SSc.

PMID- 8579977
TI  - Clinical aspects of systemic and localized scleroderma.
AB  - After the skin, the gastrointestinal tract is the most frequently affected organ
      in systemic sclerosis. Gastrointestinal symptoms already may be present early in
      the course of the disease and do not necessarily correlate with objective
      findings. Esophageal dysmotility is not specific for systemic sclerosis but
      occurs in other connective tissue diseases as well. Peripheral macrovascular
      disease was shown to be increased in patients with limited cutaneous sclerosis;
      signs of autonomic dysfunction were found in patients with the CREST (calcinosis,
      Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia)
      variant. Pulmonary involvement was shown to be moderately or severely decreased
      in 40% of a large cohort of scleroderma patients. In one study, no support was
      found for the association between pulmonary involvement and gastroesophageal
      reflux. Peripheral nerve involvement is often subclinical and might be associated
      with anti-U1-RNP and anti-topoisomerase I antibodies. Internal organs are
      seldomly affected in localized scleroderma. When occurring in childhood and
      involving an extremity, localized scleroderma can cause growth failure, resulting
      in long-term functional disability.

PMID- 8579978
TI  - Treatment of scleroderma.
AB  - Although no new agents were studied in the treatment of scleroderma this year,
      major steps were taken to improve our investigative approach to this disease. The
      American College of Rheumatology Committee on Design and Outcomes in Clinical
      Trials in Systemic Sclerosis (Scleroderma) published guidelines for clinical
      trials in scleroderma. These guidelines suggest that great care should be taken
      in the design of therapeutic trials in scleroderma so that the clinical impact of
      new treatments can be properly understood. Excellent reviews were published this
      year on how to manage scleroderma and its complications, particularly in the area
      of gastrointestinal involvement. The need to better understand the treatment of
      lung disease in scleroderma was emphasized in several reports. Provocative new
      insight into the pathogenesis of scleroderma has suggested several potential
      targets for novel approaches to treatment. The challenge for scleroderma clinical
      researchers in the future is to prioritize treatment options and organize large
      collaborative studies that are prospective, controlled, and well designed.

PMID- 8579979
TI  - Eosinophilia-myalgia syndrome, toxic-oil syndrome, and diffuse fasciitis with
      eosinophilia.
AB  - The similarity of eosinophilia-myalgia syndrome (EMS) and toxic-oil syndrome
      (TOS) to systemic sclerosis and diffuse fasciitis with eosinophilia (DFE)
      highlights the potential for environmental agents to induce autoimmune disease.
      Further, a candidate etiologic agent for EMS, 3-(phenylamino)alanine, is
      chemically similar to the aniline derivative identified in samples of oil
      implicated in TOS, 3-(N-phenylamino)-1,2-propanediol, suggesting pathogenic
      overlap. The late-stage manifestations of EMS and TOS are muscle cramping,
      arthralgia, severe fatigue, and cognitive impairment. This review focuses on the
      divergent and parallel findings in EMS, TOS, and DFE. The formation of the
      Environmentally Associated Connective Tissue Disease Study Group within the
      American College of Rheumatology will provide a forum for the development of
      registries to study suspected toxin-induced disorders.

PMID- 8579980
TI  - Overlapping syndromes, undifferentiated connective tissue disease, and other
      fibrosing conditions.
AB  - Connective tissue diseases (CTDs) frequently present with one or only a few
      symptoms, which does not allow prompt diagnosis. Raynaud's phenomenon is one of
      those symptoms. However, only a minority of patients who present with Raynaud's
      phenomenon develop a CTD. Prognostic factors for the future development of CTD in
      such patients are older age at presentation, more severe Raynaud's phenomenon,
      the presence of antinuclear antibodies, and abnormal patterns on nailfold
      capillary microscopy. Some patients have overlapping symptoms of various CTDs.
      Mixed connective tissue disease (MCTD) is the prototype of such an overlapping
      syndrome. However, during follow-up, most patients with MCTD develop a specific
      CTD, either scleroderma, systemic lupus erythematosus, rheumatoid arthritis, or
      combinations of those illnesses. Primary pulmonary hypertension is one of the
      leading causes of death in MCTD. Its treatment is insufficient, although
      continuous prostacyclin infusion may provide some relief. New therapies such as
      nitric oxide and combined heart-lung transplantation in an early stage should be
      explored. The autoimmune response to small nuclear ribonucleoproteins, which is
      highly characteristic for MCTD, interestingly shows cross-reactivity with
      retroviral antigens, and the cooccurrence of human T cell lymphotropic virus type
      I and HIV infection with MCTD has been reported. This suggests that those
      viruses, possibly by molecular mimicry, play a role in the induction of the
      disease. Fibrotic conditions related to silicone exposure still evoke much
      interest. However, most recent data do not substantiate a role for silicone gel
      breast implants in the development of autoimmune CTDs.

PMID- 8579981
TI  - Polysaccharide production by Pediococcus pentosaceus from wine.
AB  - Two polymer-forming strains of Pediococcus pentosaceus from Argentinian wines
      were grown under different conditions. Polysaccharides were produced
      independently of carbon source at the early logarithmic phase of growth. With the
      presence of ethanol and SO2, the specific polymers production was greater. The
      polysaccharides comprised of glucose, fructose and galactose, with predominant
      linkages of alpha-1,4- and alpha-1,6-glucosidic with a ratio 1:1. They contained
      approximately 5500 hexose molecules.

PMID- 8579982
TI  - The application of the WLF equation to predict lag time as a function of
      temperature for three psychrotrophic bacteria.
AB  - Many mathematical models for microbial growth rates or lag times have been
      proposed. Most of these models either predict well, but are empirical and offer
      no insight into mechanism or they reflect mechanism but are too complex or do not
      fit the data adequately. The Williams-Landel-Ferry (WLF) equation (used by
      polymer chemists) is empirical, but shows some relation to first principles, and
      hence may offer some insight into mechanism. This model also has only three
      parameters and therefore a fairly simple form. The WLF equation was fit to lag
      times derived from three datasets previously developed in our laboratory. The
      fits obtained with the WLF equation were as good as the best fits obtained with
      other models (e.g Arrhenius, Davey, response surface and square root). The WLF
      model was able to account for 98 to 99% of the variance in the three datasets,
      indicating a very good fit overall. The parameter estimates of the WLF model were
      not as highly correlated as those of some of the other models. Many of the
      models, including the WLF equation did not predict well at very long lag times.
      Weighted least squares non-linear regression improved the fit for these long lag
      times.

PMID- 8579983
TI  - Combined effect of gamma radiation and heating on the destruction of Listeria
      monocytogenes and Salmonella typhimurium in cook-chill roast beef and gravy.
AB  - The effect of heating alone (60, 65 or 70 degrees C), heating after irradiation
      (0.8 kGy) and heating after irradiation and storage for 14 days at 2-3 degrees C
      on the destruction of Listeria monocytogenes and Salmonella typhimurium in
      artifically inoculated minced cook-chill roast beef and gravy was investigated.
      Inoculated minced roast beef samples (5 g) were heated in Stomacher bags
      completely immersed in a water bath at each of the test temperatures. Survivors
      were enumerated and D and z values were determined for each of the pathogens.
      Observed thermal D values for two strains of L. monocytogenes at 60, 65 and 70
      degrees C in the absence of pre-irradiation were 90.0-97.5 s, 34.0-53.0 s and
      22.4-28.0 s, respectively, whereas thermal D values after pre-irradiation were
      44.0-46.4 s, 15.3-16.8 s and 5.5-7.8 s at 60, 65 and 70 degrees C, respectively.
      This reduction in D values provides evidence for radiation-induced heat
      sensitisation in L. monocytogenes. There was some evidence of heat-sensitisation
      of S. typhimurium at 60 degrees C, but not at either 65 or 70 degrees C. The z
      value also decreased as a consequence of pre-irradiation to a dose of 0.8 kGy
      (11.0-12.7 degrees C). The radiation-induced heat-sensitivity in L. monocytogenes
      was found to persist for up to 2 weeks storage at 2-3 degrees C prior to heating.
      As cook-chill products are intended to be reheated prior to consumption the
      results of the present study suggest that any L. monocytogenes present in a cook
      chill product would be more easily killed during reheating if it were to be
      treated with a low dose of gamma radiation during manufacture.

PMID- 8579984
TI  - Development of a flow injection analysis (FIA) immunosensor for the detection of
      Escherichia coli.
AB  - A flow injection immunoanalysis (FIA) system has been developed for the detection
      of Escherichia coli in artificially contaminated food samples. Anti-E. coli
      antibodies were covalently immobilized onto porous aminopropyl glass beads via
      glutaraldehyde activation to form an immunoreactor. After adsorption of the cells
      onto anti-E. coli antibody bound glass beads, 4-methylumbelliferyl-beta-D
      glucuronide was injected into the system which was then hydrolyzed by the
      adsorbed E. coli cells containing beta-D-glucuronidase, an enzyme which is very
      specific to E. coli and to a few other strains of Shigella. Fluorescent 4
      methylumbelliferone released from the enzymatic reaction was then detected by a
      fluorometer. Owing to the specificity of the antibody towards E. coli, the FIA
      system was very selective for detection of E. coli whereas Shigella boydii,
      another GUD-positive bacterium, did not give any response. The FIA system was
      successfully used for detecting as low as 5 x 10(7) CFU/ml E. coli in less than
      30 min and was reusable for at least 300 repeated assays. The immunoreactor
      yielded reproducible results during 3 months of experimentation if stored
      overnight at 4 degrees C in carrier buffer containing 0.05 to 0.25% Tween 20.

PMID- 8579985
TI  - Accuracy of microbial growth predictions with square root and polynomial models.
AB  - The results of growth predictions using square root and polynomial models
      published in 14 papers were studied. Errors on quantities of practical interest
      such as lag time, generation time or the time required to reach a given increase
      in number of cells, are analyzed. The distribution of these errors was examined
      with the perspective of the practical use of predictive models in food industry.
      Highly unsafe predictions and significant average errors were observed in some
      cases. A good knowledge of predictive models accuracy seems essential for their
      efficient and safe use, for example to predict the shelf life of a product. Yet,
      authors generally gave no pragmatic information on such things as the average
      relative error or the range of errors on predicted variables. Problems of
      robustness of models when tested in different conditions were noticed, which
      corroborates the necessity of a systematic validation of models on new data.

PMID- 8579986
TI  - Improvement of Salmonella detection on motility enrichment media by ferrioxamine
      E-supplementation of pre-enrichment culture.
AB  - Supplementation of buffered peptone water with ferrioxamine E in concentrations
      ranging from 0.001 to 1.0 microgram/ml significantly increased the motility of
      Salmonella on MSRV and DIASSALM semi-solid enrichment media. Zone diameters of
      swarming S. enteritidis and S. typhimurium increased more than twofold following
      use of pre-enrichment cultures supplemented with 0.01 microgram ferrioxamine
      E/ml. The activity of ferrioxamine E is similar at 37 degrees C and 42 degrees C.
      Pre-enrichment of Salmonella in a variety of foods in supplemented buffered
      peptone water, with shaking at 37 degrees C for 6 h and motility enrichment at 42
      degrees C for 16 h, enabled motile Salmonella to be detected in 1 day.

PMID- 8579987
TI  - Genomic subtraction in combination with PCR for enrichment of Listeria
      monocytogenes-specific sequences.
AB  - Genomic DNA from Listeria innocua and Listeria ivanovii was used in subtractive
      hybridization with DNA from Listeria monocytogenes involving two amplification
      strategies. Subtraction was accomplished by labelling the subtracting DNA with
      biotin and removal after liquid hybridization with tester DNA (L. monocytogenes)
      by reaction with streptavidin and phenol extraction. In one strategy, L.
      monocytogenes DNA was poly(A)-tailed with terminal transferase and amplified
      asymmetrically after subtraction. In another procedure, adapters ligated to the
      target DNA allowed symmetrical amplification after subtraction using an adapter
      specific primer; in both amplifications, the amplified products were labelled
      with biotin-modified dUTP. Southern hybridization of the amplified/subtracted
      probes with tester- and subtractor-related strains demonstrated numerous L.
      monocytogenes-specific sequences. The genome-subtracted mixed probe identified 7
      RFLP patterns among 13 strains of L. monocytogenes representing 11 L.
      monocytogenes serovars. Southern blot analysis demonstrated that the subtracted
      probe cross-hybridized to two bands among L. welshimeri strains but had little or
      no hybridization with five other species of Listeria including L. innocua, L.
      ivanovii, L. seeligeri, L. grayi, and L. murrayi. These data demonstrate that
      genomic subtraction via subtractive hybridization is a powerful method to enrich
      for specie-specific sequences in L. monocytogenes; the enriched sequences in the
      subtracted probe may be useful for typing L. monocytogenes strains by specific
      RFLP patterns or for cloning L. monocytogenes-specific sequences.

PMID- 8579988
TI  - Characteristics of some psychrotrophic Bacillus cereus isolates.
AB  - Twelve strains of Bacillus cereus isolated from different food products and
      foodborne disease outbreaks, and able to grow at temperatures < 7 degrees C, were
      characterised. Generation times at 7 degrees C varied from 9.4 h up to 75 h. Lag
      phase of the vegetative cells at 7 degrees C was strongly influenced by the
      previous temperature history of the cells. Preincubation at 37 degrees C
      increased the duration of the lag phase drastically. The heat resistance at 90
      degrees C (D90 degrees C-values in min) for spores produced at 30 degrees C
      varied from 2.2 to 9.2 min for 11 strains. One strain, however, showed a D90
      degrees C-value of > 100 min. Germination of spores in milk was delayed compared
      to those grown in brain heart infusion broth (BHI). All strains showed production
      of the diarrheal type enterotoxin in BHI. Addition of 50 IU of nisin to skim milk
      resulted in a decrease of numbers for 9 of the 12 strains tested. At a nisin
      concentration of 250 IU, a decrease in bacterial numbers was observed for all
      strains tested.

PMID- 8579989
TI  - Modified methods for the enumeration of spores of mesophilic Clostridium species
      in dried foods.
AB  - Clostridia constitute markers of limited though definite importance for the
      microbiological integrity of particular foods processed for safety, provided
      their application and the results obtained are meticulously considered and guided
      by proper ecological awareness. Their selective diagnostic enumeration in food
      specimens relies on their ability to reduce sulphite in agar media, visualised by
      the presence of ferrous cations leading to the production of black colonies. The
      composition of the medium used substantially affects the productivity of the
      procedure. We established that (1) the sulphite activity and the ferrous ion
      should be rigorously standardised; (2) tryptose is one of the appropriate
      nitrogen sources for a limited number of clostridia; (3) the basal medium should
      be free of added acetate and lactate. Black colonies obtained in the newly
      elaborated medium, termed Differential clostridial agar (DCA) should be further
      examined for morphology and metronidazole sensitivity, since some bacilli might
      mimic clostridia under the conditions of the procedure. An elegant variant of the
      technique relies on using a bottom-layer of mannitol/egg
      yolk/polymyxin/bromocresol purple agar, inoculated with macerates of food in
      buffered cysteine hydrochloride peptone saline, immediately liberally overlayered
      with freshly prepared DCA. Plates are incubated and read in tightly closed bags
      of plastic with a low oxygen permeability coefficient, which eliminates the need
      for using anaerobic jars. Colony identification is relying on assessment of
      sulphite reduction, egg yolk dissimilation, the mode of attack on mannitol and
      when required to be supported by classical other physiological traits. The
      mandatory precautions to be observed in this procedure call for extreme caution
      when introducing reference ranges ("standards") for clostridial spores in foods,
      particularly in the international commerce.

PMID- 8579990
TI  - Characterization of monascidin A from Monascus as citrinin.
AB  - Following our investigations on red pigments and monascidin co-production by
      Monascus species, the antibiotic called monascidin A was characterized as
      citrinin. Evidence was given by qualitative methods, mass spectra and NMR.
      Citrinin, a nephrotoxic agent was produced both by Monascus purpureus and
      Monascus ruber, either in submerged culture of concentrations of 270 and 340
      mg/l, respectively, or in solid state culture of concentration of 100 and 300
      mg/kg dried matter, respectively. Since citrinin is a toxic product, it is
      essential that the production of red pigments as food additives from Monascus
      spp. avoid the occurrence of citrinin.

PMID- 8579991
TI  - Application of a mathematical model to describe the behaviour of the
      Lactobacillus spp. during the ripening of a Spanish dry fermented sausage
      (Chorizo).
AB  - The evolution of Lactobacillus spp. during the curing process of dry fermented
      sausage (Chorizo), has been studied under natural climatic conditions and in a
      controlled drying chamber, with regulated temperature and relative humidity. In
      order to fully understand the development of the microorganisms in each of these
      two cases, it applied a mathematical model based on a modified Gompertz equation.
      The proposed mathematical function is easy to use and statistically appropriate.
      Furthermore, it allows the distinction to be made between the four phases which
      characterise the behaviour of these microorganisms during the curing of the
      sausage (a) latency from an initial threshold level; (b) exponential growth; (c)
      stationary state; (d) depletion to a residual level. The mathematical analysis of
      this function has highlighted certain differences in the behaviour of the
      microbial flora depending on the technological conditions to which the drying of
      the sausages is subjected. Under the climatically controlled conditions of the
      drying process, a better development of the lactobacillus spp. is observed, but
      conversely the final stage of the exponential growth is brought forward, the
      length of the stationary phase is shortened and is reached before the end of the
      drying period, at which point the marginal decline of the microorganisms becomes
      ever more reduced.

PMID- 8579992
TI  - Kinetics of interactions of lactic acid, pH and atmosphere on the growth and
      survival of Yersinia enterocolitica IP 383 O:9 at 4 degrees C.
AB  - The influence of different lactic acid concentrations (0.1, 0.3, 0.5, 0.7, 0.9,
      1.1% v/v), within pH range of 3.9 to 5.8 on the aerobic and anaerobic growth and
      survival kinetics of the virulent strain of Y. enterocolitica IP 383 O:9, was
      determined in Tryptone Soy Broth at 4 degrees C. Growth and survival data were
      analyzed and fitted by a modification of the Whiting and Cygnarowicz-Provost
      model, using the Minpack software library. Initial generation times, initial
      specific growth rates, lag times and death rates were subsequently calculated
      from the model parameters. The stability of the virulence plasmid in growing and
      surviving cells was examined using crystal violet binding, low-calcium response
      and congo red uptake. The results demonstrate the dependancy of the growth and
      survival kinetics on the interaction between the three variables. The effect of
      lactic acid on Y. enterocolitica is greater under anaerobic than aerobic
      conditions. Nevertheless, the organism was found to be more tolerant of low pH
      conditions under anaerobic atmosphere than under an aerobic atmosphere in the
      absence of lactic acid. The interaction between the variables did not lead to
      loss of the virulence plasmid in growing or non-growing cells.

PMID- 8579993
TI  - Typing of Listeria monocytogenes by random amplified polymorphic DNA (RAPD)
      analysis.
AB  - The aim of the study was to determine the effectiveness of random amplified
      polymorphic DNA analysis in typing Listeria monocytogenes from human infections.
      Twenty-five L. monocytogenes serogroup 1/2 and 70 serogroup 4 including 14
      serovar 4b(x) were typed by RAPD-PCR analysis. Six primers were used to type each
      L. monocytogenes isolate and the DNA amplification performed with supertaq DNA
      polymerase in a Hybaid Thermal Reactor. Each bacterial strain was analysed
      separately with all primers and the profiles were judged by eye and designated to
      a group by comparison to other strains. Bands were classified as major or minor.
      Based on analysis of major band patterns, the 25 serogroup 1/2 isolates gave rise
      to 12 different groups. The groups only contained serovar 1/2a or 1/2b with a
      single exception. Using minor bands all isolates could be distinguished. All the
      serogroup 4 isolates gave the same major band patterns. The 14 serovar 4b(x)
      isolates which were epidemiologically related gave identical profiles with the
      exception of one isolate. Of the remaining strains, 41 produced individual
      patterns on minor band analysis. RAPD analysis with multiple primers is low cost,
      discriminatory and is most ideally suited to testing small (< 50) numbers of
      strains. We have shown that serogroup 1/2 L. monocytogenes strains are a more
      diverse group than serovar 4b strains and RAPD-PCR will provide a technique of
      considerable value in typing L. monocytogenes in the future.

PMID- 8579994
TI  - Rapid enzymatic method for biotyping and control of lactic acid bacteria used in
      the production of yogurt and some cheeses.
AB  - Determination of enzymatic patterns of 30 strains of Streptococcus thermophilus
      and 18 strains of Lactobacillus delbrueckii subsp. bulgaricus with a rapid APIZYM
      method was carried out. Alkaline and acid phosphatase, naphthol-AS-BI
      phosphohydrolase, 10 esterases, 20 glycosidases, 61 peptidases and 2 proteases
      (trypsin and chymotrypsin) were included. The strains investigated were isolated
      from yogurt and from different starters used for different Italian cheeses. For
      S. thermophilus, all strains were positive for 3 glycosidases, 4 monopeptidases,
      9 dipeptidases, 1 tripeptidase and all were negative for 2 esterases; 9
      glycosidases; 8 peptidases and trypsin. For L. delbrueckii subsp. bulgaricus it
      was observed that all strains were positive for 2 esterases; 2 glycosidases; 11
      monopeptidases, 9 dipeptidases, 2 tripeptidases and 1 tetrapeptidase and all were
      negative for alkaline-phosphatase; 3 esterases, 7 glycosidases, 5 monopeptidases,
      2 dipeptidases. The defined enzymatic pattern of starter cultures can be used for
      predicting their suitability for dairy fermentations and for monitoring their
      stability as well as for typing.

PMID- 8579995
TI  - On the safety of lactic acid bacteria from food.

PMID- 8579996
TI  - Functional MRI: are we all moving towards artifactual conclusions? Or fMRI fact
      or fancy?

PMID- 8579997
TI  - Determination of proton metabolite concentrations and relaxation parameters in
      normal human brain and intracranial tumours.
AB  - Quantitative proton spectroscopic studies were performed on 39 volunteers and 16
      patients with intracranial tumours. Estimates of T2 were obtained in white
      matter, grey matter, cerebellum, astrocytomas and meningiomas; T1 was determined
      in white matter only. White matter values of T2 for trimethylamines, creatine and
      N-acetyl aspartate (NAA) were 309 +/- 84, 195 +/- 41 and 369 +/- 124 ms,
      respectively (mean +/- SD, n = 20). Metabolite concentrations in white matter
      were 2.0 +/- 0.4 mumol/g wet weight for trimethylamines, 7.3 +/- 1.1 for creatine
      and 11.4 +/- 1.4 for NAA. The mean concentrations of creatine and NAA in grey
      matter and all of three metabolites in cerebellum were greater than those in
      white matter. Tumour spectra were characterized by increased trimethylamines,
      reduced creatine and NAA and occasionally the presence of lactate. Meningiomas
      were further characterized by the presence of alanine. The mean T2 and
      concentration of trimethylamines in tumours was significantly greater than in
      normal brain. Creatine and NAA concentrations were decreased in all tumours. The
      longer T2 of trimethylamines and presence of alanine in meningiomas indicate that
      important differences exist in membrane and glucose metabolism within these
      tumours when compared to either astrocytomas or normal brain tissue.

PMID- 8579998
TI  - Application of homonuclear decoupling to measures of diffusion in biological 31P
      spin echo spectra.
AB  - Pulsed field gradient (PFG) spin echo 31P NMR can be used to measure diffusion
      coefficients of phosphorus-containing metabolites in vivo. In biological spin
      echo spectra, the ATP resonances are phase modulated by J-coupling between the
      three phosphorus atoms. This phase modulation may severely decrease the apparent
      signal intensity of the ATP peaks. In this paper, we describe the use of
      homonuclear decoupling during spin evolution to suppress the effects of J
      coupling in biological spin echo spectra. Phosphorous spectra of ATP and creatine
      phosphate (PCr) in solution and goldfish (Carassius auratus) skeletal muscle
      demonstrate the effectiveness of homonuclear decoupling in improving the
      effective signal-to-noise ratio of ATP. In addition, diffusion coefficients of
      ATP and PCr determined in goldfish skeletal muscle show that PFG homonuclear
      decoupled spin echo (HDSE) NMR provides accurate measures of diffusion
      coefficients.

PMID- 8579999
TI  - Image directed proton spectroscopy of gerbil brain at 7 tesla.
AB  - Image directed localized 1H NMR spectra were obtained at 7 T (300 MHz) from cubic
      volumes of less than 40 microL in the gerbil brain. Signals from cerebral
      metabolites commonly detected in other rodent species were easily assigned, and
      high resolution spectroscopy (360 MHz) of aqueous brain extracts assisted the
      tentative identification of partially overlapping resonances from lower
      concentration compounds like alanine, lysine, gamma-aminobutyrate, valine,
      leucine and isoleucine. Weak coupling at 7 T was manifest in the resolution of
      signals from the gamma-CH2 groups of glutamine and glutamate. Down-field of
      water, signals assigned to purine nucleotides were conspicuous in the extract
      spectra, but localized spectra acquired routinely in vivo, using selective
      excitation and gradient crushing (SUBMERGE) for water suppression, exhibited
      little or no signal from purines. When localized in vivo spectra were acquired
      without water suppression, however, or using a low power binomial excitation
      sequence rather than SUBMERGE, a broad signal appeared at the resonant frequency
      of purine aromatic protons. NMR experiments on the nucleotide adenosine 5'
      monophosphate (AMP) in 90% glycerol/10% D2O solution demonstrated that pre
      irradiation of the water signal even for less than 100 ms attenuated the
      nucleotide signal appreciably. This implies that the soft pulses required for
      selective excitation of water in sequences such as SUBMERGE induce spin-diffusion
      which eliminates or diminishes the signal from nucleotides in vivo.

PMID- 8580000
TI  - Chemotherapy-associated changes in 31P MRS spectra of sera from patients with
      multiple myeloma.
AB  - 31P NMR spectra were obtained from sera of 22 healthy volunteers and 20 patients
      with multiple myeloma at the time of diagnosis and repeated up to five times
      during therapy. All spectra consisted of a Pi peak (used as a reference peak) and
      two peaks from phospholipids (PL): one peak due to phosphatidylethanolamine and
      sphingomyelin (PE + SM) and a second peak due to phosphatidylcholine (PC). Prior
      to therapy, peak intensities of the phospholipids were low relative to Pi. During
      therapy leading to remission, the resonance from PL progressively increased to
      approximate the spectral pattern seen in normal sera. By contrast, in non
      responders an opposite trend was noted: the intensities of the phospholipid peaks
      became progressively reduced or remained unchanged. Long-term follow-up studies
      showed a good correlation between this 31P MRS evaluation of sera and the
      response of the disease to the therapy. In addition to the correlation with tumor
      response, our studies also show significant correlations between area,
      intensities of peaks of PE + SM, PC, and the concentrations of high-density
      lipoprotein (HDL) (correlation coefficients 0.46, 0.43, 0.59, respectively; p <
      0.001). We found that the concentration of HDL in serum of patients with multiple
      myeloma was significantly reduced. In individuals responding to therapy HDL
      levels increased to the point where there were no statistically significant
      differences between them and healthy volunteers. In patients not responding to
      therapy, HDL concentration did not increase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8580001
TI  - Inhibition of aldose reductase: 13C NMR studies in isolated peripheral nerve.
AB  - We report 13C NMR measurements of the flux through aldose reductase in isolated
      rat sciatic nerve, and its inhibition by an aldose reductase inhibitor of the
      sulphonylnitromethane class. [1-13C] galactose was used as substrate, and the
      rate of production of [1-13C] dulcitol was measured. Quantitation required the
      use both of internal extracellular, and external, standards. The mean net forward
      flux (+/- SD) was 20 +/- 11 nmol/(mL nerve water)/min (n = 10). In the presence
      of the inhibitor, flux was reduced significantly (p < 0.001) to 13% of control.
      Since dulcitol is symmetrical, an estimate of the backward flux, to [6-13C]
      galactose, is also possible; under our conditions, this was negligible.

PMID- 8580002
TI  - fMRI: does correlation imply activation?

PMID- 8580003
TI  - Clinical quiz. Haemorrhagic fever with renal syndrome (HFRS, Korean haemorrhagic
      fever).

PMID- 8580004
TI  - Growth, development and nutritional status in Japanese children under 2 years on
      continuous ambulatory peritoneal dialysis.
AB  - We examined the growth, development and nutritional status over a period of 10
      years of 15 young children (< 2 years old) on continuous ambulatory peritoneal
      dialysis (CAPD). There were 6 males and 9 females with a mean age of 12.5 months,
      mean weight of 6.3 kg, mean height of 66.2 cm at the start of CAPD and a mean
      duration of therapy of 2.6 years. Height, weight, head circumference, development
      quotient (DQ), blood chemistry and dietary intake were assessed over a period of
      10 years. The patients' mean height standard deviation score (SDS) did not change
      significantly (from -2.51 to -2.74) during CAPD therapy. The mean growth velocity
      index (GVI) during CAPD was 76.5% and correlated positively with energy intake
      but not with protein intake. The mean DQ was low (67.0%) at the start of CAPD and
      69.3% at the end of CAPD. DQ did not correlate with energy intake, GVI, head
      circumference SDS or with the weight/height ratio; however, 2 patients with low
      DQ (< 60%) had a low energy intakes. Although most patients had a low DQ, the IQ
      at 5-6 years of age was normal in all patients except 1 without cerebral disease.
      Our study showed minimal growth (delta SDS) and mental developmental (IQ) delays
      during CAPD therapy, but an adequate nutritional intake must be assured to obtain
      the above results.

PMID- 8580005
TI  - When should essential hypertension in childhood be treated and how?

PMID- 8580007
TI  - When should essential hypertension in childhood be treated and how?

PMID- 8580006
TI  - Etiology of chronic renal failure in Turkish children.
AB  - The etiology of chronic renal failure (CRF) was studied in 459 Turkish children
      (205 girls, 254 boys) for the period January 1979-December 1993. Their mean age
      at onset of CRF was 9.5 +/- 4.2 years (range 1-16 years); CRF was defined as a
      glomerular filtration rate (GFR) below 50 ml/min per 1.73 m2 for at least 6
      months. When a GFR determination was not available, the serum creatinine
      concentration was used: greater than 1 mg/dl for children aged 1-3 years, greater
      than 1.5 mg/dl for those 3-10 years and greater than 2 mg/dl for those 10-16
      years. Primary renal disorders were as follows: reflux nephropathy 32.4%
      glomerular diseases 22.2%, hereditary renal disorders 11.4%, amyloidosis 10.6%,
      urinary stones 8% and other renal disorders 15.4%. Twenty-three cases of reflux
      nephropathy (15.4%) were associated with neural tube defects (NTD) and 20 (13.4%)
      were caused by infravesical obstruction. CRF caused vesicoureteral reflux
      associated with NTD and amyloidosis are more frequent in our series compared with
      west European and Nordic countries.

PMID- 8580008
TI  - School adjustment of children with end-stage renal disease.
AB  - We examined adjustment to school of children with end-stage renal disease (ESRD)
      and the psychological condition of their mothers; 30 children on continuous
      ambulatory peritoneal dialysis (CAPD), 35 children with a transplant and 33
      healthy children were studied. A factorial ANOVA statistic found that the mean
      scores for non-academic problems (psychological factors) differed significantly
      across the three groups, being highest in CAPD children and lowest in healthy
      children. No significant differences between CAPD and transplant children were
      found for school maladjustment with academic problems, although the prevalence
      differed significantly across the groups, being highest in transplant children
      and lowest in healthy children. The mothers of children with ESRD were prone to
      feel various anxieties and dependency.

PMID- 8580009
TI  - Low-dose subcutaneous recombinant erythropoietin in children with chronic renal
      failure. Australian and New Zealand Paediatric Nephrology Association.
AB  - In a multicentre trial, low-dose subcutaneous recombinant human erythropoietin (r
      Hu EPO) was evaluated in 22 children aged 4 months to 16 years with anaemia of
      chronic renal failure over a 12-month period. A starting dosage of 50 U/kg twice
      weekly was given until a target haemoglobin of 9-11 g/dl was achieved. The dosage
      was increased by 50 U/kg per week, each 4 weeks, if the haemoglobin did not
      increase by 1 g/dl per month. When the target haemoglobin was achieved, the same
      weekly dosage was given as a single injection. After 10 weeks, the mean
      haemoglobin increased from 6.7 +/- 0.7 to 9.6 +/- 1.9 g/dl (P < 0.001) and the
      haematocrit from 19.8% +/- 2.4% to 29.3% +/- 6.3% (P < 0.001). By 4 months the
      target haemoglobin was achieved in 19 patients on 50 U/kg twice weekly and 1
      patient on 75 U/kg twice weekly. Two children with severe renal osteodystrophy
      failed to respond to 95 U/kg and 150 U/kg twice weekly. The maintenance weekly
      dose of r-Hu EPO in 9 children over 4-12 months ranged between 45 and 125 U/kg.
      The Wechsler intelligence score increased in 11 children from 92 +/- 16 to 97 +/-
      17 over the 12-month period (P = 0.007). No adverse effects were recorded. A
      starting dose of r-Hu EPO of 50 U/kg subcutaneously twice weekly is recommended
      as effective and safe for the majority of children with anaemia of chronic renal
      failure.

PMID- 8580010
TI  - Longitudinal changes in peritoneal equilibration test with or without peritonitis
      in children.
AB  - This study was conducted to evaluate longitudinal changes in the peritoneal
      equilibration test (PET) in children treated with continuous peritoneal dialysis
      (CPD). The effects of prolonged CPD and episodes of peritonitis on the PET were
      examined. PET was repeated up to five times in 12 paediatric patients who were
      subdivided into groups with and without peritonitis. In the peritonitis group (n
      = 6), the dialysate/plasma (D/P) creatinine ratio at a 4-h dwell time decreased
      progressively with time on CPD in five of six patients. In a comparison of the
      initial and final PETs performed at a mean interval of 22.8 +/- 11.6 months, the
      D/P creatinine ratio in the final PET was significantly lower than in the initial
      PET (P < 0.01). In contrast, in the non-peritonitis group (n = 6), the D/P
      creatinine ratio in the final PET was unchanged for 28.2 +/- 12.3 months from the
      initial PET. The D/Do glucose ratio at a 4-h dwell time was unchanged over time
      in each group. Thus, repeated PET measurements revealed that membrane
      permeability for creatinine was not affected by prolonged CPD itself, but
      decreased with time after episodes of peritonitis. Although the protocol for PET
      is not standardised in children, PET was useful for determining the sequential
      changes in peritoneal function in such patients on CPD.

PMID- 8580011
TI  - Immune response to influenza vaccination in children with renal disease.
AB  - Although immunization with influenza vaccine is recommended for children with
      chronic renal disease and after organ transplantation, the antibody response in
      these children has not been well described. We studied the response to the 1993
      1994 trivalent influenza vaccine in children, aged 1-21 years, with chronic renal
      failure (n = 15), end-stage renal disease requiring dialysis (n = 10), and post
      renal transplantation (n = 17). Each group's antibody response was compared with
      that of a control group (n = 7). No significant differences were found in
      seroconversion rates, percentage of patients achieving protective
      hemagglutination-inhibition titers post vaccination or change in geometric mean
      titers from pre to post vaccination between study groups and controls. These
      results suggest that pediatric patients with renal disease will respond and
      therefore will benefit from currently recommended influenza immunization.

PMID- 8580012
TI  - Prevention of tumor lysis syndrome using continuous veno-venous hemofiltration.
AB  - Tumor lysis syndrome (TLS) and renal failure remain significant causes of
      morbidity and mortality in children with newly diagnosed Burkitt's lymphoma and
      high white blood cell count acute lymphocytic leukemia (ALL) despite conventional
      management with aggressive hydration, alkalinization, allopurinol, and the slow
      introduction of chemotherapy. A subgroup of patients at very high risk for TLS
      and renal failure can be identified based on the level of serum lactate
      dehydrogenase (LDH) and urine output. We evaluated the prospective use of
      continuous veno-venous hemofiltration (CVVH), in addition to conventional
      management to prevent renal failure from tumor lysis, in three children with
      advanced abdominal Burkitt's lymphoma and in two children with high white blood
      cell count T-cell ALL who were at very high risk based on LDH and urine output.
      In this cohort of very high-risk patients, the LDH ratio (value at
      diagnosis/upper limit of normal) ranged from 0.88 to 10.3 and urine output from
      0.13 to 4.7 ml/kg per hour. CVVH was begun at a mean time of 10.5 h before
      chemotherapy was initiated. Full-dose induction chemotherapy was begun within 24
      h of diagnosis. After beginning CVVH, the uric acid levels decreased 46% prior to
      beginning chemotherapy and decreased to a mean of 4.2 mg/dl 24 h after
      chemotherapy was initiated. Four of the five patients had either no change or a
      drop in the serum creatinine. In patient one, blood urea nitrogen peaked at 58
      mg/dl, and the creatinine at 4.7 mg/dl 6 days after beginning chemotherapy with a
      subsequent return to normal. Asymptomatic hypokalemia developed in all patients.
      After beginning chemotherapy, CVVH was continued for a mean of 85 h (range 70-91
      h). No patient had complications secondary to CVVH. In summary, CVVH prevented
      renal failure secondary to TLS in 80% of these very high-risk patients. In the
      fifth patient, CVVH allowed full-dose chemotherapy to continue. The prospective
      use of CVVH could potentially decrease the morbidity and mortality associated
      with induction chemotherapy in very high-risk patients with a large tumor burden.

PMID- 8580013
TI  - Soluble circulating cell adhesion molecules in haemolytic uraemic syndrome.
AB  - Plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), E
      selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) were
      measured by enzyme-linked immunosorbent assay in four groups of children. Group 1
      consisted of 20 patients with acute diarrhoea-associated haemolytic uraemic
      syndrome (D+HUS), the aetiology of HUS being verocytotoxin-producing Escherichia
      coli infection in each case. Controls consisted of 11 patients who had previously
      had D+HUS (group 2), 12 with chronic renal failure (group 3) and 8 healthy
      controls (group 4). When compared with healthy controls, the acute D+HUS group
      had higher sVCAM-1 (median 1,875 ng/ml, range 1,200-6,450 ng/ml vs. 1,200 ng/ml,
      range 975-2,125 ng/ml), von Willebrand factor antigen, (1.9 U/ml, range 0.85-5.1
      U/ml vs. 0.55 U/ml, range 0.3-1.57 U/ml), white cell count (WBC, 14.5 x 10(9)/l,
      range 7.8-43.1 10(9)/l vs. 8.9 10(9)/l, range 5.7-10.8 10(9)/l) and neutrophil
      count (PMN, 10.1 x 10(9)/l, range 4.3-26.5 10(9)/l vs. 4.3 10(9)/l, range 3.7-6.6
      10(9)/l), all P < 0.005, and sICAM-1 was reduced (230 ng/ml, range 130-340 ng/ml
      vs. 400 ng/ml, range 260-690 ng/ml), P < 0.05. Within the acute D+HUS group there
      was a significant correlation between sICAM-1 and PMN (r = 0.56, P < 0.01). There
      was no correlation between any adhesion molecule and plasma creatinine or von
      Willebrand factor. Comparing the acute HUS group with children with chronic renal
      failure, WBC (P < 0.001), PMN (P < 0.01) and sVCAM-1 (P < 0.01) were
      significantly elevated, but there was no difference between the von Willebrand
      factor (P = 0.08) or the sICAM-1 (P > 0.1). sVCAM-1 is elevated and sICAM-1
      decreased in acute D+HUS. This pattern of altered adhesion molecule concentration
      is unlike that in adults with vasculitis and suggests that different endothelial
      regulatory factors are at play.

PMID- 8580015
TI  - The possible role of granulocyte elastase in renal damage from acute
      pyelonephritis.
AB  - During acute inflammatory processes, extracellular release of granulocyte
      elastase can contribute to subsequent tissue damage. To test our hypothesis that
      extracellular elastase release during acute pyelonephritis may contribute to
      subsequent renal parenchymal damage, we compared the intracellular and
      extracellular activities of the lysozyme elastase of human polymorphonuclear
      cells (PMN) when incubated in vitro with bacterial strains causing renal
      infection that led to either renal damage or no damage. Urine bacterial cultures
      were obtained from patients with acute pyelonephritis (flank pain, costovertebral
      angle tenderness, fever > 38 degrees C, bacteriuria, pyuria, and leukocytosis).
      Renal damage was demonstrated by cortical scarring on followup intravenous
      pyelography and/or diminished function on 131iodine hippuran renal scan. Mean
      extracellular elastase activity (mu units/PMN) was 0.15 for unstimulated PMN,
      0.07 for PMN stimulated by bacteria not associated with renal damage, and 1.20
      for the PMN stimulated by strains associated with renal damage. Mean
      intracellular elastase activity (mu units/PMN) was 3.73 for unstimulated PMN,
      3.48 for PMN stimulated by bacteria not associated with renal damage, and 3.31
      for the PMN stimulated by strains associated with renal damage. Extracellular
      granulocyte elastase activity was thus significantly higher (P = 0.0001) in PMN
      stimulated by bacterial strains associated with renal damage. Extracellular
      release of elastase may contribute to the pathogenesis of renal damage in
      pyelonephritis.

PMID- 8580014
TI  - Renal function following unilateral nephrectomy for neuroblastoma and Wilms'
      tumour.
AB  - To estimate the side effects of chemotherapy and the influence of age at the time
      of nephrectomy on renal function, we investigated renal function in 34
      uninephrectomised children with neuroblastoma (NB) or Wilms' tumour (WT). The
      results were compared with 6 controls who underwent nephrectomy for non-malignant
      disease. Study of renal function was primarily based on the clearance of inulin
      and para-aminohippuric acid (Cin and CPAH, ml/min per 1.73 m2). No significant
      differences in Cin/CPAH (mean +/- SD) were found between the NB group (90 +/-
      24/421 +/- 95), WT group (85 +/- 17/386 +/- 104) and the controls (93 +/- 13/430
      +/- 61). Children with NB and WT were divided into two subgroups according to the
      theoretical nephrotoxic risk. There was no significant difference in renal
      function between NB or between WT subgroups. Cumulative cisplatin doses in
      children with NB did not affect renal function significantly. The age at time of
      unilateral nephrectomy (< or = 2 years vs. > 2 years) was not associated with a
      higher risk of renal damage in WT children, whereas in NB children the filtration
      fraction (Cin:CPAH) was higher in younger children (mean +/- SD: 0.243 +/- 0.023
      vs. 0.191 +/- 0.041). In conclusion, uninephrectomised children with NB are
      supposed to have a higher risk of drug-induced renal impairment compared with
      those with WT. Our data do not confirm this hypothesis, since renal function was
      comparable to controls in both groups, except in younger patients with NB who
      show a high filtration fraction. Since the survival of children with NB has
      improved, a longer follow-up of their renal function in needed.

PMID- 8580016
TI  - Effect of lipoid nephrosis cytokine on glomerular sulfated compounds and
      albuminuria.
AB  - Supernatants from peripheral blood mononuclear cells cultures of 30 idiopathic,
      minimal lesion, nephrotic syndrome (IMLNS) patients in relapse and the same
      patients in remission were fractionated by gel filtration chromatography.
      Fractions eluting with carbonic anhydrase (29 kilodaltons) were infused for 5
      days at the rate of 10 microliters/h into the left renal artery of Wistar rats
      using an Alzet osmotic pump. On the last day of infusion, rats were injected with
      35sulfate (1.0 mCi/200 g) intraperitoneally and killed after 8 h. Glomeruli were
      isolated and glomerular basement membrane (GBM) obtained. There was a significant
      increase in 35sulfate uptake by GBM of the infused kidney (302 +/- 92 cpm/mg dry
      glomerular weight, mean +/- SEM) compared with the uptake seen in the
      contralateral kidney (157 +/- 36, P < 0.01) when the fraction from IMLNS patients
      in relapse was infused. No significant differences in 35sulfate incorporation
      were seen between infused kidney (166 +/- 41) and contralateral kidney (172 +/-
      64) when the same fraction from patients in remission was administered. A
      significant increase in albuminuria was seen on the last day of infusion (14.2 +/
      1.0 mg/24 h, mean +/- SEM) when supernatant factor from IMLNS patients in
      relapse was used. No significant differences in urinary albumin excretion prior
      to and after infusion were seen when the same fraction from IMLNS patients in
      remission was administered. The in vivo infusion of supernatant factor from IMLNS
      patients in relapse increased the 35sulfate uptake by GBM and augmented
      albuminuria, suggesting that the factor may have pathogenic significance in the
      proteinuria of IMLNS.

PMID- 8580017
TI  - The Ivemark syndrome: prenatal diagnosis of an uncommon cystic renal lesion with
      heterogeneous associations.
AB  - Renal dysplasia has been reported in association with a number of anatomical
      abnormalities, including pancreatic dysgenesis and hepatic anomalies. The
      combination of renal, hepatic, and pancreatic dysplasia (RHPD), also known as
      Ivemark syndrome, is rare and uniformly fatal. We report here the gross and
      histological findings in 4 cases of combined RHPD, 2 of which were detected by
      prenatal ultrasonography. Evaluation of these 4 and the other 20 reported cases
      shows that combined RHPD has considerable variability in the histological
      findings and in organ involvement. In addition, nearly half were associated with
      anomalies in other organ systems, and 11 of the 24 were familial. In this study,
      ultrasonographic and histological abnormalities were seen as early as 18.5 weeks
      gestation in 1 case.

PMID- 8580018
TI  - Resolution of hepatitis B virus-related membranoproliferative glomerulonephritis
      after orthotopic liver transplantation.
AB  - The most well-described renal disease associated with hepatitis B virus (HBV)
      infection is membranous glomerulonephritis; membranoproliferative
      glomerulonephritis is described much less frequently. The course of HBV
      associated renal disease after liver transplantation has not been described to
      date. We present a 15-year-old girl with HBV-associated membranoproliferative
      glomerulonephritis and end-stage liver disease, in whom, after cadaver liver
      transplantation, clinical and histological resolution of renal disease was
      observed. Resolution was associated with diminution of circulating HBV surface
      antigen levels.

PMID- 8580020
TI  - Calcitriol oral pulse therapy in children with renal osteodystrophy.
AB  - A 6-month protocol of oral pulse calcitriol was used in nine uraemic children (2
      14 years old) on dialysis who presented with renal osteodystrophy. Calcitriol was
      administered twice a week, 4 micrograms per dose for patients over 30 kg and 3
      micrograms for patients less than 30 kg. Plasma levels of parathyroid hormone,
      calcium, phosphorus and alkaline phosphatase were carefully controlled during the
      study. Parathyroid hormone levels decreased by 68% and 56% by the 2nd and 6th
      months of treatment in seven patients, while they remained unchanged in two
      patients with focal segmental glomerulosclerosis and massive proteinuria. Eight
      hypercalcaemic episodes from 77 determinations were observed, all of them
      recovered after 1 week of vitamin D withdrawal. We conclude that oral calcitriol
      pulse therapy is a good alternative for renal osteodystrophy in uraemic children.
      Careful monitoring of plasma parathyroid hormone and calcium is needed during
      follow-up when using this approach in paediatric patients.

PMID- 8580019
TI  - von Willebrand factor and factor XIII in children with Henoch-Schonlein purpura.
AB  - levels of von Willebrand factor antigen (vWf:Ag) and factor XIII activity (F
      XIII) were studied in relation to the severity of clinical symptoms (scored from
      0 to 3) and to immunological parameters [IgA, C3, C4, and circulating immune
      complexes (CIC)] in 16 children (7 males, 9 females, aged 3-11 years) with Henoch
      Schonlein purpura (HSP) at presentation. vWf:Ag was increased in 7 patients, F
      XIII activity was decreased in 6. In all children we found high levels of IgA,
      while C3 and C4 levels were normal; CIC were elevated in 11. vWf:Ag correlated
      with clinical score and with IgA and CIC, probably as a result of immune-mediated
      endothelial cell damage. The haemostatic alterations observed in HSP are
      important for understanding the pathophysiology of the disease.

PMID- 8580021
TI  - Effect of rifampin on Staphylococcus aureus colonization in children on chronic
      peritoneal dialysis.
AB  - The efficacy of rifampin in eliminating Staphylococcus aureus colonization was
      evaluated in a pediatric peritoneal dialysis population. Six children with
      documented nasal colonization were treated for 7 days with rifampin and
      cloxacillin. Although antimicrobial therapy eliminated nasal carriage in all
      patients, recolonization occurred in 66%. Exit site colonization proved difficult
      to eradicate with negative cultures documented in only 3 of 5 children after
      rifampin/cloxacillin therapy. Although S. aureus carriage is a risk factor for S.
      aureus infections, efforts to eradicate carriage with rifampin are hindered by
      rapid recolonization.

PMID- 8580023
TI  - Acquired glomerulocystic kidney disease following haemolytic-uraemic syndrome.
AB  - Glomerulocystic kidney disease is a rare condition, usually seen in infants and
      young children, characterised by cystic dilatation of the glomeruli. It may be
      sporadic or represent the congenital expression of dominant polycystic kidney
      disease. Glomerular cysts may also be seen in association with various syndromes
      and as a component of dysplastic kidneys. Only two cases of acquired
      glomerulocystic kidneys have been described, both in adults. The cystic change
      followed haemolytic-uraemic syndrome in one patient and systemic sclerosis in the
      other. These two conditions are closely related and may be indistinguishable
      pathologically. We report a case of acquired glomerulocystic kidney in a child
      which followed the haemolytic-uraemic syndrome. The factors leading to
      glomerulocystic kidney following haemolytic-uraemic syndrome are unknown and need
      further evaluation.

PMID- 8580022
TI  - P1 blood group antigen expression and epidemic hemolytic uremic syndrome.
AB  - P1 blood group positivity has been postulated as a host factor which may provide
      protection against the development of post-enteropathic hemolytic uremic syndrome
      (HUS). In this study, blood group status in 20 Inuit survivors of Escherichia
      coli O157:H7-associated HUS was compared with age- and sex-matched controls from
      the same community who had experienced uncomplicated diarrheal illness due to the
      same pathogen. Of 20 HUS survivors, 6 were P1 antigen positive compared with 8 of
      the 20 controls (P = 0.7). We conclude that P1 antigen positivity was not
      protective against HUS in this population. Further studies of this condition to
      clarify the role of host factors in verotoxin-induced endothelial damage are
      indicated.

PMID- 8580024
TI  - Absorption of a new oral formulation of cyclosporin A in a child on parenteral
      nutrition.
AB  - A 2-year-old child underwent renal transplantation in the presence of a post
      viral enteropathy rendering him dependent on total parenteral nutrition. As part
      of his immunosuppression, he was given a new oral formulation of cyclosporin A
      (Neoral), which he was able to absorb satisfactorily, using conventional doses,
      during the 6 weeks he was dependent on intravenous nutrition and in the face of
      intermittent severe diarrhoea. An unusual pharmacokinetic profile was observed.

PMID- 8580025
TI  - Frequently relapsing minimal change nephrotic syndrome with natural killer cell
      deficiency prior to the overt relapse of Hodgkin's disease.
AB  - A 15-year-old boy developed minimal change nephrotic syndrome (MCNS) during
      remission of Hodgkin's disease. Natural killer (NK) cell activity was practically
      absent at the onset of MCNS, with a value of 3% compared with the normal value of
      44.1% +/- 7.8% (mean +/- SD). Treatment with prednisolone resulted in transient
      remission of MCNS and partial improvement of NK cell activity. Extensive
      investigations for Hodgkin's disease were performed at 1- to 3-month intervals; a
      relapse finally became apparent 25 months after the diagnosis of MCNS. Successful
      treatment of Hodgkin's disease resulted in complete disappearance of proteinuria
      and normalisation of NK cell activity. Frequently relapsing MCNS with NK cells
      deficiency during remission of Hodgkin's disease appears to imply its subclinical
      relapse.

PMID- 8580026
TI  - Non-ketotic hyperosmolar coma complicating steroid treatment in childhood
      nephrosis.
AB  - Two nephrotic children treated with prednisone developed steroid-induced diabetes
      and non-ketotic hyperosmolar coma (NKHC). Both patients presented with
      convulsions, coma and shock. The glucose concentration of the cerebrospinal fluid
      was 425 mg/dl and 622 mg/dl, respectively. Both patients had no diabetic family
      history, but had been treated with prednisone for 4 and 8 months, receiving total
      doses of 6.6 and 10.8 g, respectively. Despite conventional therapy, both
      patients deteriorated rapidly and died several hours later. Steroid-induced
      diabetes associated with NKHC is a rare but serious complication of steroid
      therapy.

PMID- 8580027
TI  - Percutaneous transluminal renal angioplasty in neurofibromatosis.
AB  - A 9-year-old boy with hypertension was found to have neurofibromatosis associated
      with stenosis of the right renal artery. Percutaneous transluminal angioplasty
      (PTA) was performed. Immediately post angioplasty angiography showed that the
      stenosis persisted, but over the next few days his blood pressure rapidly
      decreased and remained well controlled even when treatment was discontinued. The
      captopril stimulation test, performed after PTA, confirmed the return of plasma
      renin activity to normal values. A digital subtraction aortogram, performed 2.5
      years after PTA, was unchanged. His blood pressure remained persistently normal,
      without anti-hypertensive agents. Based on these results, PTA is suggested as the
      first step in correcting renal artery stenosis due to neurofibromatosis. A
      complete anatomical resolution of the stenosis is probably not required since
      slight improvements in the renal artery lumen may be accompanied by important
      functional improvement.

PMID- 8580028
TI  - Megacystis-microcolon-intestinal hypoperistalsis syndrome.
AB  - The megacystis-microcolon-intestinal hypoperistalsis syndrome is a congenital
      disorder characterized by urinary bladder distension and hypoperistalsis
      throughout the entire gastrointestinal tract. We present a new case with the
      typical clinical, radiological, and pathological findings of the syndrome. The
      diagnosis should be suspected in a patient who present clinically with intestinal
      obstruction and urinary retention, and confirmed with imaging studies, including
      abdominal plain films, urinary tract ultrasonography, and contrast studies of the
      colon and the bladder. The prognosis is generally very poor. Our patient died
      secondary to sepsis on day 5 of life.

PMID- 8580029
TI  - Strategies to support families of children with end-stage renal failure.
AB  - The burden of care for families looking after children with end-stage renal
      failure can be considerable, especially when it involves home peritoneal dialysis
      and supplementary feeding. Good communication with the family and between team
      members delivering the multidisciplinary care is essential. Stress may be partly
      reduced by meeting the information needs and supplementing the spoken word with
      booklets, videos, tape-recorded interviews and play preparation for children.
      Families greatly appreciate a continuum of care between the hospital and
      community which is enhanced by team members visiting the home, nursery/school and
      primary care physician to impart and update knowledge. Respite care is essential
      for home dialysis patients. It can be enhanced by an evening baby-sitting service
      and the involvement of a home care renal nurse, as well as a holiday support
      strategy. Participation of the families in a regular parents support group
      provides not only an opportunity to integrate families into the unit, but also
      allows direct feedback on issues affecting the quality of care.

PMID- 8580031
TI  - The current status of screening for vesicoureteral reflux.
AB  - Reflux nephropathy is responsible for a significant percentage of end-stage renal
      disease in late childhood as well as being the most common cause of severe
      hypertension in childhood and adolescence. To prevent reflux nephropathy, it is
      imperative to discover reflux at the youngest age possible and preferably before
      any urinary tract infections have occurred. Since screening of the general
      population for reflux is not feasible, we have focused our efforts on the
      siblings of known refluxers and, more recently, the offspring of known refluxers.
      We have found high rates of reflux in both groups and have shown in the sibling
      population that early discovery of sibling reflux has significantly lowered the
      rate of renal damage compared with the index patients. It is imperative to screen
      these two risk populations at the youngest age possible, but we have recently
      made modifications in our recommendations for the older sibling and offspring.
      The results of these two screening studies are given as well as our current
      recommendations for screening for reflux in these risk groups.

PMID- 8580030
TI  - Developmental renal hemodynamics.
AB  - Renal blood flow, which is lower in the immature than in the mature animal,
      achieves adult values in human subjects by 1-2 years of age. The age-related
      increase in renal blood flow cannot be completely explained by increases in
      kidney size, since nephrogenesis is complete by 36 weeks' gestation in humans.
      Thus, other factors, especially changes in renal hemodynamics, are likely to be
      responsible for the increase in renal blood flow. The increase in renal blood
      flow appears to be directly related to the decrease in renal vascular resistance
      during the postnatal period. Decreases in the effect of renal vasoconstrictors,
      increases in the effect of renal vasodilators, or a combination of the two, may
      be responsible. Many mediators of vasoconstriction have been studied, including
      adenosine, catecholamines, endothelin, endogenous digitalis-like peptide, and the
      renin-angiotensin system. Mediators of vasodilation include endothelium-derived
      relaxing factor (e.g., nitric oxide), prostaglandins, atrial natriuretic peptide,
      dopamine, and kinins. However, the decrease in renal vascular resistance with age
      is most likely related to decreases in activity of the renin-angiotensin system
      and responsiveness to catecholamines; these effects are modulated by nitric
      oxide. Other mediators may also be important in determining the age-related
      decrease in renal vascular resistance, but their exact roles remain to be
      defined.

PMID- 8580032
TI  - Report of the American Academy of Pediatrics Section of Urology meeting.

PMID- 8580035
TI  - Clinical quiz. Hyperammonemic coma secondary to pyelonephritis.

PMID- 8580034
TI  - Is blood pressure in later life affected by events in infancy?
AB  - This article reviews experimental and clinical evidence of whether primary
      hypertension (HTN) later in life is influenced by events early in life. The
      experimental evidence is drawn from studies in inbred strains of HTN-prone rats;
      the clinical evidence is drawn from studies in children and adults of the
      influence of genetics, nutrition, and stress on adult blood pressure (BP). Adult
      BP in HTN-prone rats is significantly influenced in the preweaning period by salt
      intake and genetic factors regulating extra-cellular fluid volume, and by
      maternal-infant interactions. BPs of children track with BPs of their parents.
      Children of parents with primary HTN are insulin resistant and have lower average
      cation flux values across cell membranes as do their parents; children and their
      parents with secondary HTN do not. Children with low birth weight have a higher
      prevalence of HTN as adults than better-nourished peers. Salt intake in children
      affects BP response to stress. Average salt consumption among different cultures
      correlates with the prevalence of HTN in those cultures. Varying salt intake of
      infants and children has little influence on BP later in childhood. The evidence
      suggests simple measures that might lower the risk for HTN in HTN-prone children
      in general. However, at present we lack reliable means for identifying children
      at risk for HTN specific means to lower that risk.

PMID- 8580036
TI  - Clinical quiz. Quiescent lupus nephritis with superimposed HUS.

PMID- 8580037
TI  - Does any microscopic haematuria require urinary calcium determination?

PMID- 8580033
TI  - Host defences in continuous ambulatory peritoneal dialysis and the genesis of
      peritonitis.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) has come to be extensively used
      for the treatment of end-stage renal failure in children, and especially infants,
      such that now more than half of children on dialysis worldwide receive treatment
      by this means. Peritonitis, however, is commoner in children than in adults
      receiving treatment, and is a major source of morbidity and treatment failure in
      children started on CAPD. Only recently has the immunology of the normal
      peritoneum been studied extensively, with the need to assess the impact of the
      installation of large volumes of fluid into the peritoneal sac during dialysis.
      The main phagocytic defences of the peritoneum depend upon a unique set of
      macrophages which are present free in the peritoneal fluid but also in the
      submesothelium and in perivascular collections together with B lymphocytes in the
      submesothelial area. Both the number of macrophages per unit volume and the
      concentration of opsonic proteins, such as IgG, complement and fibronectin, are
      reduced to between only 1% and 5% when dialysis fluid is continuously present in
      the peritoneal sac. In addition, the fluids used for CAPD are toxic to both
      macrophages and to mesothelial cells. Thus minor degrees of contamination
      frequently lead to peritonitis and in addition the majority of patients have
      catheters inserted in their peritoneum which become colonised with organisms
      capable of producing exopolysaccharide (slime), which promotes adhesion of the
      organism to the plastic and protects them against phagocytic attack and the
      penetration of antibiotics. Thus the peritoneum is in a state of continual
      inflammation, as well as being a markedly more vulnerable site than the normal
      peritoneum to the entry of organisms. Whether clinical peritonitis appears in
      this state of chronic contamination probably depends on perturbation in the
      balance between host defences and the organism. Whilst Staphylococcus epidermidis
      is the commonest cause of peritonitis, Staphylococcus aureus and Gram-negative
      organisms are much more serious and more frequently lead either to temporary
      catheter removal or discontinuation of dialysis altogether. This review describes
      the peritoneal defences in relation to the genesis of peritonitis.

PMID- 8580038
TI  - Pseudotumour cerebri in an Italian girl with a kidney transplant.

PMID- 8580039
TI  - Hypercalcemia, hypercalciuria, medullar nephrocalcinosis, and renal insufficiency
      in a toddler with Down syndrome.

PMID- 8580040
TI  - IgA nephropathy--Henoch-Schonlein purpura--common pathogenesis.

PMID- 8580041
TI  - Three cases of Henoch-Schonlein purpura preceded by IgA nephropathy.

PMID- 8580042
TI  - Renal failure in the neonate associated with in utero exposure to non-steroidal
      anti-inflammatory agents.

PMID- 8580043
TI  - What are the indications for renal biopsy in acute nephritic syndrome?

PMID- 8580044
TI  - Multidimensional assessment and causal modelling in teacher stress research: a
      commentary.

PMID- 8580045
TI  - Teacher stress research: problems and progress.
AB  - There is a reasonably large body of published research evidence available which
      indicates that teaching is a 'highly' or 'extremely highly' stressful occupation
      for up to one-third of its professionals. Generalisations such as this one,
      however, are wrought with problems. These problems, for instance, range from
      confusion about the definition of stress through to how it is to be measured.
      They include methodological problems inherent in some of the research used to
      examine the area of teacher stress and as well include, for example, confusion
      about the effect of mediating variables in the production of stress and strain.
      This paper examines some of the more important pervasive research problems in
      current research on teacher stress and makes some suggestions for research
      progress.

PMID- 8580046
TI  - Individual differences in story comprehension and recall of poor readers.
AB  - This study sought to identify poor readers and characterise weaknesses in their
      knowledge and use of story structure in comprehension and recall. Eighty year 3
      children, 20 good readers and 60 poor readers, were selected from an initial pool
      of children based on factor analysis of scores from three measures of reading
      ability. The poor readers were then divided into relatively homogeneous
      subgroups, using eight additional measures of language-reading comprehension,
      according to a numerical classification procedure. This procedure helped identify
      specific weaknesses in their language-reading comprehension. All children
      listened to three stores and retold the stories under free and probe recall
      conditions. Story recalls were analysed using the STein and Glenn story grammar.
      Comparison of recalls between the good readers and each of the subgroups of poor
      readers showed that poor readers in two subgroups evidenced reduced sensitivity
      to story structure. The children in these subgroups recalled less of the stories
      overall, recalled less information from story grammar categories to varying
      extents, and showed patterns of category recall that differed from those of
      normal readers. Children in one of the subgroups also displayed poor perception
      of causal relations across story episode boundaries. These results provide
      evidence of marked heterogeneity in poor readers' story comprehension and recall.
      Certain subgroups of poor readers may have qualitatively different problems
      processing stories, relative to other poor readers, which may require a more
      concerted approach to instruction in story structure.

PMID- 8580047
TI  - Personal computers and process writing: a written language intervention for deaf
      children.
AB  - This study was concerned with the effectiveness of word processing as a written
      language intervention for primary-age deaf children. Subjects were 14 children in
      two primary school deaf-unit classes matched in terms of age, gender, and degree
      of hearing loss. A quasi-experimental design incorporating multiple-group
      baselines with pre- and post-tests enable all subjects to receive the
      intervention while maintaining experimental control. Samples of children's
      written language were collected at the end of each phase in the study.
      Experienced teachers of deaf children rated five dimensions of the quality of the
      written language samples, while a speech and language therapist judged other
      linguistic qualities of the writing. Significant improvements in quality ratings
      over the course of the study indicated that the word processing intervention had
      led to improvements in the children's written language skills. These results
      confirm the effectiveness of word processing as an adjunct to the process writing
      approach to written language instruction for deaf children.

PMID- 8580048
TI  - Motivational styles in English and mathematics among children identified as
      having special educational needs.
AB  - This study is concerned with the identification, development and prevalence of
      three different motivational styles: learned helplessness, self-worth motivation
      and mastery orientation in two National Curriculum core subjects: English and
      mathematics. These three motivational styles are concerned with the ways in which
      children respond in the face of difficult and challenging educational tasks.
      Using Craske's (1988) procedures, a total of 437 children in their first year of
      secondary school (aged 11-12) were categorised into one of the three motivational
      styles. Children with special educational needs were identified using a battery
      of cognitive ability tests (Thorndike, Hagen & France, 1986). This study compares
      the prevalence of each motivational style in English and mathematics in children
      of different abilities and presents empirical support for the view that learned
      helplessness and self-worth motivation are more prevalent among children
      identified as having special educational needs. Further analyses indicate that:
      overall, learned helplessness and self-worth motivation are more prevalent in
      English than mathematics; learned helplessness is more prevalent among girls and
      self-worth motivation among boys in mathematics. Implications for teachers in
      developing teaching strategies which foster mastery orientation in their children
      are discussed.

PMID- 8580049
TI  - Perceptions and experiences of bullying in younger pupils.
AB  - A pictorial questionnaire was devised to explore definitions and experiences of
      bullying with Year 2 pupils (6-7 years). The questionnaire was given individually
      to 60 pupils from two schools, balanced by sex. Various indicators suggested that
      the children responded reasonably consistently to the questions; they had an
      understanding of what bullying meant, irrespective of questionnaire format, which
      included indirect as well as direct forms; and they had some understanding of the
      time frame of reference. The reports of being bullied were quite frequent,
      consistent with an extrapolation from the age trend reported by Whitney & Smith
      (1993), to younger pupils. However, despite evidence for general consistency in
      responses, many children extended their definition of bullying to include
      fighting behaviour and aggressive behaviour, which was not necessarily repeated,
      or qualified in other ways. The implications of this for possible age changes in
      definitions of bullying, and hence for interpretations of the apparent decline in
      experiences of bullying with age, are considered.

PMID- 8580050
TI  - Radiotherapy: effective treatment at low cost!

PMID- 8580051
TI  - Sarcoidosis and cancer.

PMID- 8580052
TI  - The molecular genetic basis of childhood neoplasia.

PMID- 8580053
TI  - Radiation therapy: are we getting value for money?
AB  - The aim of this study was to examine the long term cost effectiveness of
      radiotherapy (RT) in the treatment of cancer at the Department of Radiation
      Oncology, Westmead Hospital, from its inception in 1980 to December 1993. A
      Kaplan-Meier survival curve was constructed for all patients treated by RT during
      the study period. The area under this curve represented the average survival. The
      total number of life years was calculated by multiplying the number of patients
      by the average survival. Costing for one RT treatment field had previously been
      derived. The cost included capital costs, building costs and overheads as well as
      labour, goods and services, and operating costs. The cost per field was
      multiplied by the total number of fields given each year and the yearly total
      summed to give the total cost. The total cost was divided by the number of life
      years to give a cost per life year. An overall percentage survival gain was
      estimated from departmental results and the literature. Cost per life year gained
      (LYG) was derived by dividing the cost per life year by the percentage survival
      gain. Sensitivity analysis was performed with best- and worst-case survival
      scenarios, and high and low cost per field estimates. A total of 9868 patients
      were treated by radiotherapy between January 1980 and December 1993. Median
      follow-up was 4.2 years. Median survival was 2 years. The 5- and 10-year survival
      rates were 35% and 22%, respectively. The area under the survival curve (the
      average survival) was 4.75 years. The total number of life years of survival was
      thus 4.75 x 9868 = 46,873. In 1993, the cost per field was $71.52 (Australian
      dollars). The total number of fields treated in the study period was 758,097.
      Hence, the total cost in 1993 dollars was $54,219,097. The survival gain
      (excluding skin cancer) with RT was 16.1% and the cost/LYG was $7186. Sensitivity
      analysis of best and worst case scenarios gave costs/LYG of $3920 and $15,632
      respectively. Efficient resource allocation can be aided by examining the
      relative cost-effectiveness of different prevention and treatment strategies. RT
      is shown to have a lower cost/LYG than other accepted treatments in current
      practice. Other major treatment modalities should be subjected to the same
      scrutiny of cost effectiveness as has been applied to RT.

PMID- 8580055
TI  - Cyclosporin plus doxorubicin, vincristine and etoposide in the treatment of
      refractory non-Hodgkin's lymphoma: a phase II study.
AB  - In an attempt to circumvent clinical multidrug resistance, we conducted a Phase
      II trial of cyclosporin plus combination chemotherapy in patients with relapsed
      or refractory non-Hodgkin's lymphoma. Thirteen patients, all of whom had been
      previously treated with a doxorubicin-containing regimen, received doxorubicin 50
      mg/m2 intravenous continuous infusion (IVCI) over 96 h (days 1-4), vincristine 2
      mg i.v. (day 1), and etoposide 75 mg/m2 i.v. daily for 4 days (days 1-4). Four
      days prior to chemotherapy, patients received a loading dose of cyclosporin (0.88
      mg/kg i.v. over 2 h), followed by a maintenance dose (1.8 mg/kg per day IVCI for
      9 days). Cyclosporin dose escalation was permitted, conventionally defined
      therapeutic levels of cyclosporin were achieved; this drug was well tolerated at
      these doses. The study was closed due to a poor response rate; only one patient
      achieved a complete remission of 33 weeks' duration. Grade 3 and 4 toxicities
      included gastrointestinal haemorrhage (one patient), sensory neuropathy (two
      patients), stomatitis (two patients), and transaminase elevation (one patient).
      Asymptomatic grade 1-2 toxicities (elevated creatinine and transaminase levels)
      occurred in 33% of patients. There were no treatment associated deaths. Prolonged
      neutropenia and thrombocytopenia were the primary haematological toxicities.
      Although the addition of cyclosporin at this dose and schedule did not improve
      response rates in this patient group, future trials using higher doses of
      cyclosporin with combination chemotherapy may warrant further investigation.

PMID- 8580054
TI  - Increasing and planned dose intensity of doxorubicin, cyclophosphamide and
      etoposide (ACE) by adding recombinant human methionyl granulocyte colony
      stimulating factor (G-CSF; filgrastim) in the treatment of small cell lung cancer
      (SCLC). Medical Research Council Lung Cancer Working Party.
AB  - The aim of this Phase II study was to test the feasibility of intensifying
      standard chemotherapy in the treatment of small cell lung cancer (SCLC) by
      reducing the interval between cycles from 3 to 2 weeks by adding recombinant
      human methionyl granulocyte colony-stimulating factor (G-CSF; filgrastim) to
      shorten the duration of neutropenia following each cycle. Thirty-two patients
      with SCLC were prescribed six cycles of 2-weekly doxorubicin 50 mg/m2 and
      cyclophosphamide 1 g/m2 on day 1, and etoposide 120 mg/m2 i.v. on days 1, 2 and 3
      (ACE), plus filgrastim in a fixed dose of 300 micrograms s.c. on days 4-14 of
      each cycle. Three patients died during the treatment period and a further nine
      had chemotherapy terminated before the sixth cycle, all nine because of toxicity.
      All 32 patients have been followed up for at least 21 months; 14 (44%) were alive
      at 12 months and the median survival period was 356 days. Of the 127 intervals
      between cycles of chemotherapy, 74 (58%) were of the prescribed 14 days, 18 (14%)
      of 15-20 days, 25 (20%) of 21 days, and 10 (8%) were longer. The results were
      best during the first four cycles, during which 71% of the 83 intervals were of
      14 days and a further 10% were less than 21 days. The main reason for delay was
      haematological toxicity in 37 of the 53 instances. Symptoms of myelosuppression
      occurred in 23 patients, but at 14 days after a cycle of chemotherapy, all 127
      available neutrophil granulocyte counts were normal. Twenty-one patients received
      blood transfusion and five platelet transfusion. The only adverse effects
      attributed to filgastrim were episodes of rash, throat swelling, anorexia and
      shivering, affecting one patient. We conclude that the policy of adding
      filgrastim allows the dose intensity of ACE chemotherapy to be increased by
      reducing the intervals between cycles. The findings reinforce those of a parallel
      study involving lenograstim.

PMID- 8580056
TI  - An audit of the use of agreed treatment protocols at a major centre for cancer
      treatment.
AB  - The treatment that a patient with cancer receives may vary considerably,
      depending on where and by whom the treatment is given. Agreement on treatment
      protocols for patients undergoing cancer treatment is clearly a desirable aim.
      Within departments this will result in greater uniformity of treatment, lead to
      greater safety, facilitate the evaluation of treatment strategies, and improve
      cost effectiveness. We have examined prospectively the extent to which treatment
      protocols are being adhered to within a major cancer treatment centre. One
      hundred newly registered cancer patients were studied. The results are
      encouraging, with complete adherence to protocol for 84. Of the 16 occurrences of
      deviation from a protocol this was unavoidable for three and of minor importance
      for five, being relatively small changes in radiotherapy dose reflecting
      particular clinical situations. Thus, eight deviations represented serious
      departures from the protocols by the responsible clinicians. This study has shown
      that in a major cancer treatment centre the development of agreed treatment
      protocols is both feasible and practical.

PMID- 8580057
TI  - Clinical applications of composite and realtime megavoltage imaging.
AB  - The versatility of electronic portal imaging devices (EPIDs) is best demonstrated
      by their ability to perform novel megavoltage imaging protocols, which are still
      pertinent to good radiotherapy practice. This paper examines two such techniques:
      composite and realtime imaging. Our EPID can be programmed to acquire and
      manipulate images very easily, allowing images from segmented treatment protocols
      to be mixed and displayed, giving a composite image of the effective treatment
      result. Its use for verifying the efficacy of spinal shielding using a segmented,
      offset collimator technique is described. By acquiring images very quickly,
      realtime imaging sequences can be obtained and used to analyse anatomical
      movement within a single treatment field. The technique is employed here to
      investigate movement in radical lung, breast, abdomen, pelvis and thyroid
      treatments. Our results show that the protocol is vital for treatment sites
      involving the lungs; changes up to 5 mm have been observed in the maximum lung
      depth for breast treatments, and displacements up to 16 mm for radical lung
      treatments. It is also useful in other anatomical sites for ensuring that no
      movement occurs.

PMID- 8580058
TI  - Prevention of tumour seeding following thoracoscopy in mesothelioma by
      prophylactic radiotherapy.
AB  - To determine the usefulness of prophylactic radiotherapy following thoracoscopy
      or pleural aspiration in patients with mesothelioma we reviewed the case notes of
      patients treated at St Mary's Hospital between 1990 and 1994. Twenty patients
      have received treatment to 38 sites and tumour seeding was prevented in all
      patients available for follow-up. Four patients acted as their own controls by
      developing nodules at untreated sites. Prophylactic radiotherapy is highly
      effective in preventing tumour seeding in mesothelioma.

PMID- 8580059
TI  - VACOP-B chemotherapy for high grade non-Hodgkin's lymphoma in pregnancy.
AB  - A patient presenting with high grade non-Hodgkin's lymphoma in the second
      trimester of pregnancy was treated with combination chemotherapy, with successful
      outcome for both mother and foetus.

PMID- 8580060
TI  - Bone marrow infiltration by a parietal lobe grade III oligodendroglioma.
AB  - We report a patient with oligodendroglioma metastases 1 year after tumour
      debulking and postoperative radiotherapy to the parietal lobe primary. This
      treatment controlled the patient's tumour locally. Distant recurrence was
      manifest by back pain, weight loss and malaise. The serum alkaline phosphatase
      was raised and a bone scan showed generalized increased uptake. Bone marrow
      trephine revealed infiltration by oligodendroglioma. Bone marrow infiltration by
      gliomas is very rare. If the trephine had not been performed it might have been
      assumed that he had a disseminated second primary tumour.

PMID- 8580061
TI  - Oxyphil cell carcinoma of the parathyroid: a rare cause of hyperparathyroidism.
AB  - Oxyphil carcinoma of the parathyroid is an extremely rare tumour, only two
      previous patients having been reported. We report a 55-year-old woman with this
      condition, who presented with a picture of hyperparathyroidism, including
      hypercalcaemia, hypercalciuria, hypophosphataemia, increased alkaline
      phosphatase, and bony lesions. Biopsy of a bone lesion was consistent with brown
      tumour. Fine needle aspiration cytology and subsequent operative histology of the
      parathyroid lesion showed an oxyphil cell tumour with malignant characteristics.
      Following excision, the patient made a good recovery, complicated only by
      postoperative hypocalcaemia.

PMID- 8580062
TI  - Radiation reaction recall following simvastatin therapy: a new observation.
AB  - A 60-year-old woman was treated postoperatively for carcinoma of the gall bladder
      with a split course of radiotherapy. The tumour dose (TD) was 61.2 Gy in 34
      fractions delivered by an anterior and two lateral wedge fields with 60Co; the
      Dmax was 70% of TD for the anterior field and 150% of the TD at the thin edge of
      the wedges. She also underwent 5-FU and leucovorin chemotherapy. No skin reaction
      was seen during radiotherapy or in 1 year of follow-up. A year after radiotherapy
      she was treated for hypercholesterolaemia by simvastatin. Within 2-3 days a
      severe skin and subcutaneous reaction developed in the lateral radiation fields
      but not in the anterior field. To our knowledge, recall of skin radiation
      reaction after simvastatin therapy has not been previously reported.

PMID- 8580063
TI  - The radiological appearances of small cell (oat cell) carcinoma of the
      oesophagus.
AB  - We present three patients with primary small cell (oat cell) carcinoma of the
      oesophagus from a clinical and radiological point of view and review the
      radiological appearances of previously reported cases. The features of this rate
      neoplasm are variable, but extensive circumferential oesophageal wall thickening
      associated with luminal widening should raise the possibility of this diagnosis.

PMID- 8580064
TI  - Extramedullary plasmacytoma of maxillary sinus with later involvement of the gall
      bladder and subcutaneous tissues.
AB  - We recently encountered a patient with extramedullary plasmacytoma (EMP)
      originating in the maxillary air sinus, who developed subcutaneous tissue and
      gall bladder involvement 2 years after initial local radiotherapy. Treatment with
      melphalan, prednisone and interferon led to a rapid and sustained regression of
      the gall bladder tumour. Complete remission was obtained by subsequent regional
      radiotherapy to the subcutaneous tumours in the extremities. Progression of
      plasmacytoma to the hepatobiliary system and subcutaneous tissues is quite rare
      and the effects of chemo- and radiotherapy on these lesions have not been fully
      elucidated. This study demonstrated that EMP can be well controlled and complete
      remission obtained by various therapeutic strategies, even though this tumour
      develops widespread dissemination.

PMID- 8580065
TI  - A rare site and appearance for lymphomatous recurrence.
AB  - A patient with a recurrence of large cell lymphoma is reported. There was psoas
      muscle involvement, which showed ring enhancement post-intravenous contrast on CT
      scan. Ring enhancement in skeletal muscle infiltration by lymphoma has not been
      described previously.

PMID- 8580066
TI  - Staging of Burkitt's lymphoma and response to treatment monitored by PET
      scanning.
AB  - Positron emission tomography (PET) is an imaging technique using biological
      tracers (18-fluorine fluorodeoxyglucose (FDG)), whose uptake into tumour cells is
      increased. Previous studies carried out in patients with lymphoma have shown that
      PET is an accurate method of staging disease and that a high pre-treatment FDG
      uptake that is abolished by the end of chemotherapy is associated with a good
      clinical response. This case report demonstrates that clinical PET scanning can
      be especially useful in staging patients with lymphoma in whom there is extensive
      extranodal and marrow involvement, and that PET can follow changes in tumour
      viability over a very short time span.

PMID- 8580067
TI  - Primary non-Hodgkin's lymphoma of the thyroid with bone marrow infiltration at
      presentation.

PMID- 8580068
TI  - Tyrosine-phosphorylated forms of Ig beta, CD22, TCR zeta and HOSS are major
      ligands for tandem SH2 domains of Syk.
AB  - The protein tyrosine kinase Syk plays an important role in signal transduction
      from the B cell antigen receptor and possibly also from the TCR. We have examined
      the binding specificity of Syk-derived SH2 domains in vitro and found that the
      tandem SH2 domains have two major ligands in activated Ramos B cells as well as
      in activated Jurkat T cells. The SH2-binding proteins in Ramos B cells were
      identified as the tyrosine-phosphorylated forms of the Ig alpha beta heterodimer
      and of CD22. Binding to the Ig alpha beta heterodimer seems to occur
      predominantly via Ig beta, indicating that the two receptor components might
      couple to distinct signaling pathways. In Jurkat T cells one of the SH2-binding
      proteins represents the tyrosine-phosphorylated TCR zeta chain. The identity of
      the second SH2 ligand, called HOSS, is not known. HOSS is discussed as a putative
      member of the receptor family characterized by the immunoreceptor tyrosine-based
      activation motif.

PMID- 8580069
TI  - Pleiotropic effects of Bcl-2 on transcription factors in T cells: potential role
      of NF-kappa B p50-p50 for the anti-apoptotic function of Bcl-2.
AB  - Bcl-2 functions to repress apoptosis by regulation of genes which encode proteins
      required for programmed cell death and by interference with peroxidative damage.
      We investigated the interrelationship between expression of bcl-2 and regulation
      of transcription factor DNA binding activities in the 2B4 T cell hybridoma and IL
      2-dependent CTLL T cell line. Over-expression of bcl-2 in 2B4 resulted in
      enhanced basal levels of activator protein (AP)-1, octamer binding factor (Oct)
      1, lymphoid enhancer binding factor (LEF)-1, RelA-p50 and NF-kappa B p50-p50 DNA
      binding activities. After apoptotic signaling, down-regulation of AP-1, NF-AT and
      Oct-1 binding activities was observed in control 2B4 and CTLL, whereas
      suboptimal, but higher, levels of these transcription factors were found in bcl-2
      transfected cells, potentially promoting cell survival. Furthermore, after
      apoptotic signaling, expression of bcl-2 led to differential changes of NF-kappa
      B levels, resulting in a decrease in RelA-p50 and an increase in NF-kappa B p50
      p50, altering the ratio of these DNA binding activities such that now p50-p50
      markedly predominated in both 2B4-Bcl-2 and CTLL-Bcl-2. Apoptotic signaling in
      the presence or absence of Bcl-2 resulted in induction of the RelB-p50
      heterodimer in 2B4. The changes in NF-kappa B/Rel levels raise the possibility
      that this family of transcription factors may play an important role in the
      regulation of apoptosis.

PMID- 8580070
TI  - Characterization of an alternative superantigen binding site expressed on a renal
      fibroblast cell line.
AB  - It is well established that the bacterial superantigens bind to both TCR beta
      chain and, with moderate affinity, to MHC class II molecules. Class II-bearing
      cells bind the superantigen and present the superantigen to T cells expressing
      certain TCR beta-chain variable region alleles. We have observed that the
      superantigen staphylococcal enterotoxin (SE) B binds to COS-1, an African green
      monkey kidney fibroblast-like cell line. This cell line fails to express class II
      and the binding of SEB is saturable. Scatchard analysis of radiolabeled ligand
      binding data reveals a binding affinity for COS of 51 nM, while binding to DR1
      transfected L cells is measured at 150 nM. Further analysis shows that SEB bound
      to COS cells, unlike SEB bound to DR1-bearing L cells, is not recognized by T
      cells in the presence or absence of accessory cytokines or anti-CD28. Studies
      carried out with chemical cross-linking agents show that radiolabeled SEB
      associates with a membrane protein of approximately 85 kDa. These studies suggest
      that the alternative superantigen binding molecule (p85) binds SEB with an
      affinity roughly equivalent to SEB binding by class II molecules, but at a site
      which does not permit recognition by the TCR.

PMID- 8580071
TI  - IL-4 producing CD4+ TCR alpha beta int liver lymphocytes: influence of thymus,
      beta 2-microglobulin and NK1.1 expression.
AB  - The present report describes developmental, phenotypic and functional features of
      unconventional CD4+ TCR alpha beta lymphocytes. In C57BL/6 mice, the majority of
      liver lymphocytes expressing intermediate intensity of TCR alpha beta (TCR alpha
      beta int) are CD4+ NK1.1+ and express a highly restricted TCR V beta repertoire,
      dominated by V beta 8 with some contribution by V beta 7 and V beta 2. Although
      these cells express the CD4 co-receptor, they are present in H2-1 A beta (A beta)
      /- gene disruption mutants but are markedly reduced in beta 2-microglobulin (beta
      2m)-/- mutant mice and hence are beta 2m dependent. Thymocytes expressing the
      CD4+ NK1.1+ TCR alpha beta phenotype are also beta 2m contingent, suggesting that
      these two T lymphocyte populations are related. The CD4+ NK1.1+ TCR alpha beta
      lymphocytes in liver and thymus share several markers such as LFA-1+, CD44+,
      CD5+, LECAM-1- and IL-2R alpha-. The CD4+ NK1.1+ TCR alpha beta int liver
      lymphocytes were not detected in athymic nu/nu mice. We conclude that beta 2m
      expression is crucial for development of the CD4+ NK1.1+ TCR alpha beta int liver
      lymphocytes and that thymus plays a major role. CD4+ TCR alpha beta int liver
      lymphocytes were also identified in NK1.1- mouse strains, there lacking the NK1.1
      marker. We assume that the NK1.1 molecule is a characteristic marker of the CD4+
      TCR alpha beta int liver lymphocytes in NK1.1+ mouse strains, although its
      expression is not obligatory for their development. The liver lymphocytes from
      beta 2m+/-, but not from beta 2m-/-, mice are potent IL-4 producers in response
      to CD3 or TCR alpha beta engagement and the IL-4 production by liver lymphocytes
      was markedly reduced by treatment with anti-NK1.1 mAb. We conclude that the CD4+
      NK1.1+ TCR alpha beta int liver lymphocytes are capable of producing IL-4 in
      response to TCR stimulation.

PMID- 8580072
TI  - Presentation of peptides by cultured monocytes or activated T cells allows
      specific priming of human cytotoxic T lymphocytes in vitro.
AB  - The conditions favouring effective specific cytotoxic T lymphocyte (CTL) priming
      have been exploited to set up a simple and reproducible method to induce a
      primary CTL response in vitro. We report that cultured monocytes, as well as
      activated T cells, pulsed with exogenous HLA-A2 binding immunogenic peptides, can
      induce primary peptide-specific CTL responses in vitro in a Th-independent
      manner. Primary viral peptide-induced CTL were HLA-A2 restricted, and recognized
      both peptide-pulsed target cells and targets infected with recombinant vaccinia
      virus expressing viral endogenous antigens. In addition, both cultured monocytes
      and activated T cells primed peptide-specific CD8+ T cells depleted from the
      CD45RO+ memory cell fraction. The efficiency of CTL priming by monocytes was
      dependent upon the strong up-regulation of class I, adhesion and co-stimulatory
      molecules occurring spontaneously upon in vitro culture. The inability of
      unseparated peripheral blood mononuclear cells to mount a peptide-specific CTL
      response could be reverted by direct co-stimulation of responding CD8+ T cells by
      soluble B7.1 or a stimulatory anti-CD28 antibody, that allowed a specific
      response to take place. Although co-stimulation via the B7-CD28 interaction
      appeared sufficient to trigger CTL responses, it was not essential for CTL
      priming, since neither anti-B7.1 mAb nor soluble CTLA-4 inhibited induction of
      primary CTL response. This new method for induction of specific CD8+ T cell
      response in vitro may be exploited in adoptive immunotherapy in cancer or in HIV
      infected patients.

PMID- 8580073
TI  - Human glycoprotein HGP92 induces cytokine synthesis in mouse mononuclear
      phagocytes.
AB  - HGP92 has been shown to enhance in vitro and in vivo the bactericidal and
      tumoricidal activity of mouse macrophages. In this study we investigated the
      effect of HGP92 on the accumulation of cytokine mRNA in mouse inflammatory,
      peritoneal macrophages and the monocytic cell line J774. HGP92 significantly
      enhanced the level of cytokine mRNA for IL-1 alpha, IL-1 beta, IL-6, IL-10, IL
      12, TNF-alpha and GM-CSF during the first 24 h of the incubation. This effect
      triggered by HGP92 was comparable to that obtained with lipopolysaccharide (LPS),
      which is a strong cytokine inducer. This accumulation of cytokine mRNA in
      macrophages was correlated with secretion of IL-6 and TNF-alpha in cell
      supernatant. The release of IL-6 was HGP92 concentration dependent over a range
      of 0.3-10 micrograms/ml with a maximum production obtained after a 24 h
      incubation of inflammatory macrophages with HGP92. This effect was shown not to
      be due to contamination of HGP92 by LPS since inflammatory macrophages from
      C57BL/6 mice were responsive to HGP92 pretreated with polymyxin B sulfate and
      unresponsive to heated HGP92. Stimulating activity of HGP92 was confirmed using
      macrophages from C3H/HeJ mice. These results suggest that HGP92 might modulate
      the immune responses by increasing cytokine production by macrophages.

PMID- 8580074
TI  - Resident CD4+ alpha beta T cells of the murine female genital tract: a
      phenotypically distinct T cell lineage that rapidly proliferates in response to
      systemic T cell activation stimuli.
AB  - A population of CD4+ cells has been identified in the murine female genital tract
      (FGT). Phenotypic studies of FGT CD4+ cells demonstrate that they express CD3 and
      that the majority of these cells are alpha beta TCR+Thy-1+. Most of the Thy
      1+CD4+alpha beta TCR+ cells resemble memory T cells based on their expression of
      CD44, L-selectin and CD45RB antigens. The vast majority of Thy-1+CD4+alpha beta
      TCR+ FGT cells are CD5+ and all of them are B220-. Systemic stimuli including
      infection with Trypanosoma brucei brucei, injection with anti-CD3 epsilon, or
      bacterial superantigens staphylococcal enterotoxin A or B cause a rapid
      accumulation of CD4+ cells in the FGT exceeding that observed for CD4+ cells in
      spleen and lymph nodes (LN). Expansion of the FGT CD4+ cells, which are
      phenotypically distinct from the splenic and LN CD4+ T cells, is due to local
      proliferation rather than an influx of cells from the circulation. The CD4+
      population in the FGT of adult nu/nu mice is dramatically reduced, indicating its
      thymic dependency. In lpr/lpr mice, FGT CD4 cells do not display changes
      characteristic of splenic or LN CD4 cells in the same animals. These findings
      demonstrate that the CD4+ cells of the murine FGT are thymic dependent, but that
      they constitute a T cell lineage that phenotypically and, probably functionally,
      is distinct from other peripheral CD4+ T cell populations.

PMID- 8580075
TI  - Analysis of proteolipid protein (PLP)-specific T cells in multiple sclerosis:
      identification of PLP 95-116 as an HLA-DR2,w15-associated determinant.
AB  - Multiple sclerosis (MS) is a putative autoimmune disease that is linked with HLA
      DR2,w15. Proteolipid protein (PLP) is a candidate autoantigen in MS, but the
      disease-associated epitopes have not been determined. Using overlapping and non
      overlapping PLP peptides, we have studied the T cell response to the major
      hydrophilic domain PLP 85-159 in the peripheral blood of MS and healthy subjects
      (HS). Short-term T cell lines (TCL) were selected against each peptide using
      microwell plates and the frequency of peptide-specific TCL was estimated. PLP 95
      116-specific TCL were most efficiently generated and the frequency was
      significantly higher in MS compared with HS (P < 0.05). When compared between
      DR2,w15+ and DR2,w15- MS, TCL frequency to PLP 95-116 was significantly higher in
      DR2,w15+ MS (P < 0.005) and TCL reactive to the overlapping peptide 105-124 were
      also increased in DR2,w15+ MS (P < 0.025). Using DR gene-transfected L cells, we
      could show that the DRB1*1501 product of the DR2 haplotype presents PLP 95-116 to
      TCL selected against the peptide. These results imply that PLP 95-116 represents
      a major epitope for the DR2,w15+ MS.

PMID- 8580076
TI  - CD44 plays a co-stimulatory role in murine T cell activation: ligation of CD44
      selectively co-stimulates IL-2 production, but not proliferation in TCR
      stimulated murine Th1 cells.
AB  - The murine CD44 receptor family is thought to be involved in a variety of
      lymphocyte functions, including lymphopoesis, lymphocyte homing and cell
      migration. Herein, we show that murine CD44 also plays a role as a co-stimulatory
      molecule for the activation of CD4+ T cells. Ligation of CD44 by mAb enhanced IL
      2 production of long-term cultured, anti-CD3-stimulated Th1 cell lines. Moreover,
      anti-CD44 mAb synergized with anti-CD28 mAb in exerting this effect. A synergism
      of anti-CD28 and anti-CD44 mAb to co-stimulate IL-2 production was also observed
      in anti-CD3-triggered, freshly isolated splenic CD4+ T cells. Blocking
      experiments with cyclosporin A indicated that the intracellular pathways used by
      the CD28 and CD44 molecules appear to be different. In contrast to the effects on
      the IL-2 production of Th1 cells, neither anti-CD44 mAb alone nor the combination
      of anti-CD44 with anti-CD28 were able to induce proliferation of anti-CD3
      triggered Th1 cells. In accordance, triggering of CD44 and/or CD28 by mAb was not
      sufficient to reverse the previously described 'proliferative block'. This term
      describes the unresponsiveness of Th1 cells against IL-2, which occurs when Th1
      cells are triggered by anti-CD3 in the absence of co-signals. These data lead us
      to propose a model of Th1 cell activation which includes two functionally
      different types of co-signals: one for IL-2 production and a separate one for
      proliferation.

PMID- 8580077
TI  - A radiosensitive APC activity dissociates IL-2 secretion and activation-induced
      cell death by autoreactive T cell hybridomas.
AB  - T cell hybridomas were generated from a LEW rat T cell line specific for the
      uveitogenic peptide bov-B1 of bovine retinal S-antigen. Using these autoreactive
      hybridomas, IL-2 production and activation-induced cell death (AICD) were
      dissociated as outcomes of activation. The self-reactive hybridomas secrete IL-2
      and undergo AICD in response to antigen presented by non-irradiated syngeneic
      splenocytes, whereas antigen presentation by irradiated splenocytes induced only
      AICD. IL-2 production by a non-self reactive hybridoma was unaffected by
      irradiation of the APC. Pretreatment of the APC with phorbol ester or
      lipopolysaccharide and IL-4 protected their ability to induce IL-2 secretion
      after gamma-irradiation. Although the co-stimulation-blocking reagent CTLA-4-Ig
      mimicked the effect of gamma-irradiation by preventing IL-2 secretion but not
      AICD, B7 expression on the APC was not radiosensitive, nor did co-stimulation,
      provided 'in trans' with a B7-expressing third-party cell, reconstitute antigen
      specific hybridoma IL-2 secretion in response to irradiated APC. In summary, the
      data show that IL-2 secretion and AICD of a self-reactive T cell hybridoma can be
      dissociated as consequences of TCR occupancy in the presence of a functional co
      stimulatory signal. It is proposed that the signals producing these events are
      transduced through the TCR-CD3 complex alone and reflect the differential
      outcomes of high- and low-affinity interactions.

PMID- 8580078
TI  - In situ dormancy of B lymphocytes programmed for an IgE antibody response and
      their sudden release from unresponsiveness under in vitro conditions.
AB  - Priming of CBA/J mice with different doses of antigen has a profound effect on
      the ratio of IgE versus IgG antibodies appearing upon immunization. Repeated
      injections of minute doses induce IgG and high titers of IgE antibodies. Large
      doses elicit a high IgG but a very low IgE antibody titer. In order to study the
      modalities for activation and inactivation of IgE-producing B cells, an in vitro
      culture system was established in which spleen cells from animals primed with
      keyhole limpet hemocyanin were re-stimulated with antigen. In contrast to the
      expectation from the in vivo situation, spleen cells from animals immunized with
      large doses of antigen and virtually lacking IgE antibodies produce high amounts
      of IgE antibodies upon re-stimulation in vitro. The titers in spleen cell
      cultures from mice primed with minute doses remain proportional to the response
      measured as serum antibodies. In accordance with the induction of high amounts of
      IgE antibodies in spleen cell cultures from mice primed with large doses, the
      frequency of IgE antibody-secreting cells was raised drastically, approximately
      1000-fold. The in vitro response is a true anamnestic response. The sudden
      appearance in high frequency of IgE antibody-forming cells among spleen cells
      isolated from primed mice which have high IgG but virtually no IgE antibody
      titers is as yet unexplained and the origin of the B epsilon memory cells has not
      yet been traced. The answer might be crucial for our understanding of the down
      regulation of the IgE immune responses.

PMID- 8580079
TI  - CD40 cross-linking inhibits specific antibody production by human B cells.
AB  - Ligation of CD40 on B cells is a co-stimulatory signal for proliferation,
      antibody secretion, heavy chain switching and rescue from apoptosis after somatic
      mutation in the germinal centre. The importance of these manifold responses to
      CD40 activation for humoral immunity is exemplified by the inability of boys with
      X-linked hyper IgM syndrome to make IgG, IgE or IgA due to a mutation in in the
      gene coding for CD40 ligand (CD40L). In the present study, we have investigated
      the effect of CD40 ligation on specific antibody production by human B cells to
      influenza virus. The antibody response was T cell dependent and specific for the
      strain of influenza virus used as antigen. Addition of either CD40 mAb or
      recombinant trimeric CD40L profoundly inhibited specific antibody production.
      Antibody production by unseparated tonsillar mononuclear cells and by T-depleted
      B cells stimulated with antigen in the presence of T cell replacing factor were
      equally inhibited with CD40 antibody showing that the effect was due to ligation
      of CD40 on B cells rather than blocking of T cell help. The specific antibody
      detected in these experiments was mostly IgG with little or no IgM and was
      obtained from surface IgM B cells consistent with activation of a secondary
      (memory) response. Co-stimulation of tonsillar B cells with CD40 antibody and
      anti-IgG induced proliferation of IgG+ B cells. These results suggest that CD40
      ligation can inhibit specific antibody responses and stimulate proliferation in
      the same IgG+ (memory) B cell subpopulation. Addition of CD40 antibody during the
      first 24-48 h of the response was required for inhibition, suggesting that the
      effect was on early B cell activation and/or proliferation required for antibody
      production. There was no correlation, however, between the ability of CD40 mAb to
      stimulate proliferation and inhibit antibody production. We suggest that early
      activation of CD40 in the specific antibody response inhibits the formation of
      plasma cells and promotes instead the generation of memory cells.

PMID- 8580080
TI  - Immunoblot analysis of cellular expression of Bcl-2 family proteins, Bcl-2, Bax,
      Bcl-X and Mcl-1, in human peripheral blood and lymphoid tissues.
AB  - The ability of Bcl-2 to inhibit apoptotic cell death is well established. Several
      homologues of the bcl-2 gene, such as bax, bcl-x or mcl-1, have recently been
      identified. Like Bcl-2, both Bcl-XL and Mcl-1 appear to function as repressors of
      apoptotic cell death, whereas Bax facilitates it, indicating possible
      interactions among them in the control of cellular survival. To investigate the
      in vivo role of expression of bcl-2 gene family products, immunoblot analysis
      using corresponding specific antisera was performed for peripheral blood cells
      and some lymphoid tissues in humans. We demonstrated that all Bcl-2 family
      proteins were expressed at various levels in hematolymphoid cell subpopulations
      isolated from peripheral blood, tonsil, spleen and thymus. Lymphoid expression of
      Bcl-2 family proteins tended to increase following activation, but declined with
      time in culture. Loss of Bcl-2 in cultured lymphoid cells was especially marked.
      Sole expression of Bax, but not other members of the Bcl-2 family, was observed
      on neutrophils, seemingly reflecting their shortest life-span among blood
      leukocytes. The results support the notion that a balance of expression of Bcl-2
      family proteins may regulate the life and death of hematolymphoid cells at
      different stages of cell differentiation and activation.

PMID- 8580081
TI  - A T cell lymphoma can provide potent co-stimulatory effects to T cells that are
      not mediated by B7-1, B7-2, CD40, HSA or CD70.
AB  - Dominant second signals for T cell activation can be generated through
      interactions between CD28 and CTLA-4 on T cells with their co-stimulatory ligands
      B7-1 and B7-2 on APC. Nevertheless, some B7-negative cell lines appear capable of
      providing second signals to T cells, illustrating that B7-independent co
      stimulatory pathways may exist. One such cell line, the peptide-transporter
      defective T lymphoma RMA-S, was investigated in the present study, to determine
      the origin of the co-stimulatory effects it provides. RMA-S can support clonal
      expansion of purified CD4 or CD8 T cells from unprimed mice activated with
      concanavalin A (ConA) or immobilized anti-CD3. Nevertheless, RMA-S does not
      express B7-1 or B7-2, nor does it express other known co-stimulatory molecules,
      i.e. CD40, gp39, CD70 and HSA. Also, co-stimulation provided by RMA-S could not
      be blocked by antibodies or fusion proteins specific for these co-stimulatory
      molecules, excluding their participation. However, RMA-S' co-stimulatory activity
      is dependent on adhesive interactions. RMA-S is incapable of IL-2 production in
      the presence of ConA or anti-CD3, but T cells co-stimulated by RMA-S produce IL-2
      and IFN-gamma upon anti-CD3- or ConA-induced activation. Furthermore, co
      stimulation of antigen-specific T cell proliferation of both class I- and class
      II-restricted T cell clones can be provided by RMA-S, and RMA-S can preclude
      induction of anergy by 1-ethyl-3-(3-dimethyl amino propyl)carboiimide-fixed APC
      in a class II-restricted T cell clone. The results suggest that potent co
      stimulatory pathways can be induced by cellular interactions between a T
      lymphoma, RMA-S and T cells, not involving gp39, CD40, CD70, HSA, B7-1 (CD80) or
      B7-2 (CD86). Characterization of the molecules involved is in progress.

PMID- 8580082
TI  - Ligand binding kinetics of IL-2 and IL-15 to heteromers formed by extracellular
      domains of the three IL-2 receptor subunits.
AB  - Studies on the binding of IL-2 to its receptor (IL-2R) have generally been
      limited to receptors expressed on cell surfaces. This has hampered detailed
      kinetic and mechanistic studies at the molecular level. We have prepared the
      soluble extracellular domains of all three receptor subunits (called alpha, beta
      and gamma) by recombinant techniques and have used these to perform detailed
      kinetic studies of their binding properties using the technique of surface
      plasmon resonance. We describe a novel approach whereby the receptors are
      assembled on an antibody surface, being held by an epitope engineered into the C
      terminus of each of these domains. Thus the receptors are oriented naturally
      leading to homogeneous ligand binding kinetics. We have characterized the
      interactions of the heteromeric complexes of these subunits with mouse and human
      IL-2 and their analogs, as well as the recently discovered cytokine, IL-15. We
      have also studied the extracellular domains of the mouse receptor subunits for
      the first time and have used these as well as mouse-human hybrid receptors to
      probe the mechanism of assembly of these complexes. We show that no additional
      proteins are required to reproduce the properties of these complexes in vitro. In
      addition, kinetic studies with site-specific analogs of IL-2 and the mouse-human
      receptor hybrids clearly indicate that the extracellular domains of alpha and
      beta can together readily bind ligand with kinetic properties distinct from those
      of the constituent subunits. In contrast, a complex containing ligand and the
      extracellular domains of beta and gamma was comparatively difficult to assemble
      and required prolonged exposure to IL-2. Our method enabled us to calculate the
      stoichiometry of these complexes and to determine that anchoring these subunits
      is necessary to efficiently drive complex formation. The kinetic and equilibrium
      differences between the mouse and human receptor complexes, and between IL-2 and
      IL-15 binding to these receptors clarify the roles of the alpha and gamma
      subunits in the differential response of cells to different cytokines that may be
      present simultaneously in the environment.

PMID- 8580083
TI  - The protein tyrosine kinase Fyn activates transcription from the HIV promoter via
      activation of NF kappa B-like DNA-binding proteins.
AB  - Protein tyrosine kinase p59fyn (Fyn) associates with the TCR-CD3 complex, which
      suggests that Fyn plays a significant role in the signal transduction involving
      TCR complex. In addition to cellular genes, viral promoters such as the HIV long
      terminal repeat (LTR) are also activated upon T cell activation. To elucidate the
      functional significance of Fyn in the expression of viral promoters, we
      transfected a Fyn-expression vector together with a reporter plasmid containing
      the chloramphenicol acetyltransferase gene driven by HIV LTR into a human T cell
      line, Jurkat. In this assay, Fyn stimulated the promoter in HIV LTR when the
      transfected cells were treated with both concanavalin A and PMA as an antigen
      mimic stimulation. This activation required the intact SH2 domain of Fyn.
      Mutational analysis of HIV LTR showed that the NF kappa B binding sites were
      responsible for this effect. Electrophoretic mobility shift assays and UV cross
      linking experiments showed that activation of T cells by anti-CD3 antibody
      induced four kappa B-binding proteins (50, 60, 65 and 100 kDa) in Fyn
      overexpressing cells more efficiently than in the parental cells. Our results
      suggested that Fyn was able to regulate expression of a subset of genes via kappa
      B-binding proteins upon T cell activation.

PMID- 8580084
TI  - Migration pathways of CD4 T cell subsets in vivo: the CD45RC- subset enters the
      thymus via alpha 4 integrin-VCAM-1 interaction.
AB  - The present investigation examines the localization and migration of purified T
      cell subsets in comparison with B cells, CD8 T cells and CD4+ CD8- single
      positive thymocytes. CD4 T cell subsets in the rat are defined by mAb MRC OX22
      (anti-CD45RC), which distinguishes resting CD4 T cells (CD45RC+) from those
      (CD45RC-) which have encountered antigen in the recent past--subpopulations often
      referred to as 'naive' and 'memory'. Purified, 51Cr-labelled CD45RC+ CD4 T cells
      broadly reflected the migration pattern of CD8 T cells and B cells. Early
      localization to the spleen was followed by a redistribution to mesenteric lymph
      nodes (MLN) and cervical lymph nodes (CLN), B cells migrating at a slightly
      slower tempo. There was almost no localization of these subpopulations to the
      small or large intestine [Peyer's patches (PP) excluded]. In contrast, CD45RC-
      CD4 T cells (indistinguishable in size from the CD45RC+ subset) localized in
      large numbers to the intestine; they were present here at the earliest time point
      (0.5 h), persisted for at least 48 h but did not accumulate, indicating a rapid
      exit. Numerically, localization of CD45RC- CD4 T cells in the MLN could be
      accounted for entirely by afferent drainage from the intestine. Unexpectedly,
      CD45RC- CD4 T cells (but not other subsets) localized and accumulated in the
      thymus. In vivo treatment with mAb HP2/1 against the integrin alpha 4 subunit
      inhibited almost entirely CD45RC- CD4 T cell migration into the PP (98.1%),
      intestine (87.1%), MLN (89.1%) and thymus (93.5%); migration into the CLN was
      only reduced by half. To distinguish between recognition of MAdCAM-1 and VCAM-1
      by alpha 4-containing integrins, recipients were treated with mAb 5F10 against
      rat VCAM-1. Except for the thymus and a small reduction in CLN, localization of
      CD45RC- CD4 T cells was unaffected; entry to the thymus was almost completely
      blocked (92.3%) by anti-VCAM-1. The results indicated (i) that CD45RC- CD4 T
      cells alone showed enhanced localization to the gut and PP, probably via alpha 4
      beta 7-MAdCAM-1 interaction; (ii) that many CD45RC- cells entered non-mucosal LN
      independently of alpha 4 integrin or VCAM-1; and (iii) that entry of mature
      recirculating CD45RC- CD4 T cells into the thymus across thymic endothelium was
      apparently regulated by alpha 4 integrin-VCAM-1 interaction.

PMID- 8580085
TI  - APO-1 (CD95)-dependent and -independent antigen receptor-induced apoptosis in
      human T and B cell lines.
AB  - Certain B and T cell lines respond to activation signals, e.g. through the
      antigen receptor, by undergoing apoptotic cell death. In T cells it has been
      recently shown that TCR-mediated apoptosis involves APO-1/Fas(CD95) receptor
      ligand interaction. To investigate whether the TCR-CD3 complex can trigger
      alternative apoptosis pathways we generated subclones of the T cell line Jurkat
      which were completely resistant towards APO-1-mediated apoptosis. These JurkatR
      cells differed phenotypically from sensitive parental JurkatS cells only by the
      lack of APO-1 protein expression. Although JurkatR cells responded normally to
      anti-CD3 stimulation by expression of APO-1 ligand they failed to undergo anti
      CD3-induced apoptosis. Thus, in Jurkat cells APO-1-mediated apoptosis was the
      main, and might be the only, mechanism for anti-CD3-induced cell death. However,
      BL-60 B cells, highly sensitive to anti-IgM-induced apoptosis, did not use the
      APO-1 receptor-ligand system because they failed to express APO-1 ligand mRNA.
      Taken together, our results suggest that malignant T and B cell lines may use APO
      1 receptor-ligand-dependent and -independent antigen receptor-induced apoptosis
      pathways respectively. Similarly, differential pathways may be used by T and B
      cell subsets.

PMID- 8580086
TI  - Effect of IL-7 treatment on Leishmania major-infected BALB.Xid mice: enhanced
      lymphopoiesis with sustained lack of B1 cells and clinical aggravation of
      disease.
AB  - The Xid immunodeficiency was characterized by a total lack of B1 cells and
      reduced numbers and functions of B2 cells. In BALB.Xid mice, this defect results
      in an reduced susceptibility against infections with parasites such as
      Trypanosoma cruzi and Leishmania major. Since IL-7 acts on the B cell compartment
      by stimulation of pre-B cell proliferation, we analyzed the effect of recombinant
      IL-7 on L. major infection in BALB.Xid mice. After application of a single dose
      of IL-7 simultaneously with the infection, the clinical course in BALB.Xid mice
      was markedly aggravated, resembling that of normal BALB/c mice. IL-7-induced
      disease promotion was accompanied by an up to 100-fold higher parasite load in
      several tissues of these mice. When cytokine production of purified, L. major
      specific CD4+ T cells from lesion-draining lymph nodes was examined, the IFN
      gamma production seen in untreated BALB.Xid mice was suppressed in IL-7-treated
      animals. One of the major effects of IL-7 treatment in the lymphoid organs of
      BALB.Xid mice was the increase of the total number of B220, sIgM and MHC II
      positive cells. These cells belonged to the B2 subset, since cells expressing
      surface molecules characteristic for B1 cells (Mac-1 and Ly-1) remained absent in
      spleens, lymph nodes and the peritoneum. In conclusion, selective up-regulation
      of B2 cells by IL-7 in the absence of B1 cells is associated with disease
      aggravation in L. major-infected BALB.Xid mice.

PMID- 8580088
TI  - Purification of exo- and endoinulinase from crude inulinase extract for the
      analysis of fructans.
AB  - This paper describes a technique for rapid and easy separation of a crude
      inulinase extract into exo- and endoinulinase from a commercially available
      inulinase stock (Novozym 230 from Novo Nordisk A/S) by means of non-denaturating
      polyacrylamide gel electrophoresis. The purified enzymes were tested with inulin.
      Characterization of the reaction products was done by high-performance thin-layer
      chromatography, size exclusion chromatography and semi-preparative reverse-phase
      high-performance liquid chromatography.

PMID- 8580087
TI  - Acyclic oligonucleotide analogues.
AB  - Acyclic analogues of oligothymidylate and oligoadenylate and their alternating
      copolymers were synthesized to study their thermal melting, their stability
      against snake venom phosphodiesterase and their primer/template properties using
      the Klenow fragment of the Escherichia coli DNA polymerase I enzyme. Acyclic
      dodecaadenylate (GlyA)12 hybridized to dodecathymidylate p(dT)12, and the complex
      presented a sharp melting with a Tm at 24 degrees C. This association was
      confirmed by circular dichroism curves which were similar to those of the natural
      oligonucleotide duplexes in A-conformation. (GlyA)12 proved very stable against
      snake venom phosphodiesterase hydrolysis. The reaction rate was more than 10,000
      times slower than that of p(dT)12. (GlyA)12 served as a primer for the Klenow DNA
      polymerase. When (GlyA)12 was complexed with the poly(dT) template, the enzyme
      polymerized dATP but the reaction was much slower than with the (GlyT)12 primer.
      Molecular modelling of atactic (GlyA)12.(dT)12 of the A-conformation indicates
      that this conformation is energetically possible.

PMID- 8580089
TI  - The liquid amide transfer model and the unfolding thermodynamics of small
      globular proteins.
AB  - In this paper, the solid cyclic dipeptide model developed by Murphy and Gill is
      analysed in order to point out that, apart from general thermodynamic features
      shown by well-characterized small globular proteins, only the polar and apolar
      contributions to the net denaturation heat capacity change are necessary to
      calculate the so-called protein stability curve, delta dGzero versus temperature.
      We propose that these specific heat capacity contributions can be determined in a
      reliable manner by a group additivity analysis of the transfer process of liquid
      amides from pure liquid phase into water. This suggests that the unfolding
      process, thought of as the transfer of amino acid residues from the protein
      'core' to contact with water molecules, can be modelled based on the transfer
      process of organic amides. The reliability of the model is tested in comparison
      with literature data.

PMID- 8580090
TI  - Effects of manganese (II) on Bacillus licheniformis ATCC 9945A physiology and
      gamma-poly(glutamic acid) formation.
AB  - Bacillus licheniformis ATCC 9945A was cultivated in shake flasks using citrate
      (12 gl-1), glutamate (20 gl-1) and glycerol (80 gl-1) as carbon sources for cell
      growth and gamma-poly(glutamic acid) (gamma-PGA) production. The effect of the
      MnSO4 concentration in the medium over a range from 0.0 to 615 microns was
      studied. The number of viable cells increased for all concentrations of MnSO4
      from approximately 10(5) to 10(9) colony-forming units (cfu) ml-1 by the early
      stationary phase (24 h). However, after 50 h, the cell viability decreased
      rapidly for relatively lower MnSO4 concentrations (0.615 and 0 microns). The
      utilization of carbon sources by B. licheniformis was greater for cultures
      containing 33.8 and 615 microns MnSO4 relative to cultures with no added MnSO4.
      For example, cultures with 615 microns MnSO4 utilized 37, 54 and 93% and cultures
      with no added MnSO4 utilized 19, 10 and 17% of glutamate, glycerol and citrate,
      respectively. The gamma-PGA volumetric yield increased from approximately 5 to 17
      gl-1 for corresponding increases in MnSO4 concentration from 0 to 33.8 microns
      and then decreased at higher MnSO4 concentrations. The stereochemical content of
      gamma-PGA was found to vary inversely with MnSO4 concentration, and ranged from
      59 to 10% L-glutamate units for MnSO4 concentrations of 0 and 615 microns,
      respectively. For all of the MnSO4 concentrations investigated, the gamma-PGA
      molecular weights decreased rapidly as the gamma-PGA volumetric yield
      simultaneously increased for cultivation times from 24 to approximately 50 h. Mw
      and Mn values after approximately 50 h cultivation times, determined by gel
      permeation chromatography (GPC), were 1.3 to 1.6 and 0.5 to 0.8 million g mol-1,
      respectively. A complex gamma-PGA molecular weight distribution that appeared
      bimodal by GPC analysis due to the presence of a low-molecular-weight product
      fraction was observed in cultures containing 33.8 and 61.5 microns MnSO4 at
      extended cultivation times. A high-molecular-weight fraction and the
      unfractionated gamma-PGA sample from the 33.8 microns MnSO4 culture contained 13
      +/- 4 and 30 +/- 1% L-repeat units, respectively. A relationship between the
      product molecular weight and its stereochemical composition was thus established.

PMID- 8580091
TI  - Amino acid grafting of beta-lactoglobulin mediated by phosphorus oxychloride.
AB  - beta-Lactoglobulin was phosphorylated with 80 mol of POCl3/mol protein in the
      presence of triethylamine and amino acids or their esters added at a total molar
      excess of 6 mol base/mol POCl3. The extent of phosphorylation was reduced when
      the amino acids replaced triethylamine as the base. Arginine and lysine were
      grafted to protein molecules in amounts proportional to the beta-lactoglobulin
      phosphorylation, while histidine grafting was very weak. The electrophoretic
      patterns of the modified proteins showed increased negative charges, reduced
      isoionic points and slight dimerization. The emulsifying properties of the
      modified proteins were improved.

PMID- 8580092
TI  - Conformation and interactions of all-D-, retro-all-D- and retro-bombolitin III
      analogues in aqueous solution and in the presence of detergent micelles.
AB  - Bombolitins are five structurally related heptadecapeptides which lyse
      erythrocytes and liposomes and enhance the activity of phospholipase A2. The
      conformational properties of the all-D-, retro-all-D, and retro-L-analogues of
      bombolitin III were investigated by circular dichroism (CD) and two-dimensional
      1H-nuclear magnetic resonance (NMR) techniques. In water, all three sequences are
      in a random conformation and aggregate to various extents depending on pH and
      concentration. The two enantiomeric retro-sequences exhibit a higher propensity
      to form beta-aggregates, while the D-analogue of the native sequence tends to
      form aggregates of alpha-helices. In the presence of an excess of sodium dodecyl
      sulfate (SDS), the peptides fold into an amphiphilic alpha-helical conformation
      (left-handed in the case of the all-D sequences). NMR studies on the L-retro
      analogue indicate that the helical segment is localized in the central part of
      the sequence. Combined CD and surface tension measurements indicate that the
      critical micellar concentration of SDS is raised in the presence of peptide and
      that helical folding occurs before micelle formation. These results are
      interpreted in terms of formation of peptide-detergent complexes. It is estimated
      that the helical structure forms when 40-50 molecules of detergent are bound to
      each peptide molecule. These data and our previous results in vitro biological
      tests confirm that the ability to form amphiphilic helices is the major
      determinant of biological activity of bombolitins.

PMID- 8580093
TI  - Hagfish biopolymer: a type I/type II homologue of epidermal keratin intermediate
      filaments.
AB  - In contrast to most intermediate filaments (IF) which function intracellularly or
      constitute epidermal appendages, the single massive (approximately 60 cm length,
      approximately 3 microns width) IF-rich 'thread' biopolymer synthesized by the
      specialized hagfish gland thread cell is released extracellularly via holocrine
      secretion to interact with mucins and seawater, thereby modifying the
      viscoelastic properties of the copious mucous exudate. Recently, using the
      Pacific hagfish (Eptatretus stouti, class Agnatha), a jawless scaleless marine
      vertebrate of ancient lineage, we determined that the deduced amino acid sequence
      of one thread IF chain (alpha, 66.6 kDa, native pI 7.5) contained an atypical,
      threonine-rich central rod domain of low identity (< 30%) with other vertebrate
      IF types, but that the N- and C-terminal domains exhibited several keratin-like
      features. From these and other unexpected characteristics, it was concluded that
      hagfish alpha is best categorized as a type II homologue of an epidermal keratin.
      We now report the deduced sequence of a second thread IF subunit (gamma, 62.7
      kDa, native pI 5.3) which is co-expressed and co-assembles in vitro with alpha in
      a 1:1 ratio. As was found for alpha, the N- and C-terminal domains of gamma have
      keratin-like parameters, but the central rod has low identity to IFs of types I-V
      (< 31%), a cephalochordate IF (< 29%) and invertebrate IFs (< 20%) and no
      particular homology to type I or type II keratins. Central rod identity between
      gamma and alpha is also low (approximately 23%), as is typical of comparisons
      between different rod types but atypical of similar rod types (> 50%). The
      central rods of both gamma and alpha lack the 42-residue insert of helix 1B
      present in lamins and invertebrate IFs, have unusually high threonine contents
      (gamma, 10%; alpha, 13%) compared to other IF types (2-5%), contain a number of
      unexpected residues in consensus conserved sites, and employ a L12 segment of 21
      residues rather than the 16 or 17 residues found in keratins. Theoretical
      analyses indicate that the hagfish molecules exist as coiled coil heterodimers
      (alpha/gamma) in which the chains are parallel, in axial register, and stabilized
      by significant numbers of ionic interactions. Fast Fourier-transform analyses
      revealed that the linear distribution period of approximately 9.55 for basic and
      acidic residues in other IF chains is not completely maintained, partly due to
      the high threonine content. The threonine residues occupy mainly outer sites b,
      c, f in the heptad substructure, possibly abetting parallel alignment of
      thousands of IFs within the thread, interactions with mucins at the thread
      periphery, and hierarchical IF chain assembly. It is suggested that the gamma and
      alpha chains from this most primitive extant vertebrate are type I and type II
      homologues of epidermal keratin chains, possibly related to early specialized
      keratins.

PMID- 8580094
TI  - In vitro antiviral activities of sulfated polysaccharides from a marine microalga
      (Cochlodinium polykrikoides) against human immunodeficiency virus and other
      enveloped viruses.
AB  - A marine microalga, Cochlodinium polykrikoides, produces extracellular sulfated
      polysaccharides. Isolation and purification of the polysaccharides were
      accomplished by precipitation with ethanol and Cetavlon, followed by DEAE
      cellulose column chromatography (polysaccharides A1 and A2). These
      polysaccharides, which were homogeneous when analysed by both ultracentrifugal
      and electrophoretic methods, were composed of mannose, galactose, glucose and
      uronic acid, together with sulfate groups (S = 7-8% w/w). Both A1 and A2
      inhibited the cytopathic effect of influenza virus types A and B in MDCK cells,
      that of respiratory syncytial virus types A and B in HEp-2 cells, that of human
      immunodeficiency virus type 1 in MT-4 cells; and, except A1 for herpes simplex
      virus type 1 and A2 for parainfluenza virus type 2 in HMV-2 cells, the
      cochlodinium polysaccharides showed no antiviral activity against parainfluenza
      virus types 2 and 3, measles virus, mumps virus or herpes simplex virus type 1 in
      HMV-2 cells. No cytotoxicity for host cells was observed with these
      polysaccharides at a concentration of 100 micrograms ml-1. Inhibitory effects on
      various viruses were achieved at concentrations that were not markedly inhibitory
      to the blood coagulation process.

PMID- 8580095
TI  - A report on the hazards encountered when taking neonatal cleft palate impressions
      (1983-1992).
AB  - A questionnaire was sent to 193 United Kingdom Hospital Consultant Orthodontists,
      in order to survey their individual involvement and clinical protocols for
      neonatal cleft palate impressions. Information regarding any untoward events that
      might have been experienced with this procedure during the period 1983-1992 was
      sought. Sixteen episodes where withdrawal of an impression had been extremely
      difficult and five respiratory obstructions due to an impression fragment were
      reported. Eighty-nine cyanotic events were reported, of which four resulted in
      asphyxiation, although none progressed to a fatality. Factors such as the level
      of consultants' experience or the choice of impression material used did not
      appear to be contributory.

PMID- 8580096
TI  - Crystal bonding--an adhesive system with a future?
AB  - The primary objective of this investigation was to evaluate the crystal bonding
      technique and to: (1) study the effect on crystal size, coverage, and morphology
      of altering the concentration of lithium sulphate in a crystal growth solution;
      (2) investigate the potential for reattachment of brackets, following the use of
      the crystal growth technique; (3) assess the deterioration of the crystal growth
      conditioning solution with time; (4) investigate the influence of polyacrylic
      acid enamel pretreatment on the bond strength subsequently achieved with the
      crystal growth technique; and (5) confirm that the use of crystal growth
      solutions to attach orthodontic brackets, results in minimal enamel surface
      change on debond when compared to the acid etch technique. The results of the
      study suggest that altering the lithium sulphate concentration of the crystal
      growth solution results in little alteration in the size, morphology, and
      coverage of crystal produced. The crystal growth technique allows reattachment of
      orthodontic brackets with no obvious deterioration in bond strength and the
      crystal growth solution shows little deterioration in performance after storage
      for 2 years. However, the hope that the use of the crystal growth technique might
      be a routine and valid alternative to the acid etch technique could not be
      confirmed.

PMID- 8580097
TI  - An ex vivo study of self-, light-, and dual-cured composites for orthodontic
      bonding.
AB  - It was postulated that using a dual-cured composite to bond orthodontic brackets
      could result in bond strengths comparable with those of chemically-activated
      materials and higher than those for light-activated materials. The shear bond
      strength of four composite resins used to attach mesh-backed orthodontic brackets
      was measured at 24 hours and following mechanical insult in the ball-mill.
      Analysis of variance and an SNK range test showed that at 24 hours Dual-cured
      Porcelite gave a significantly higher mean bond strength than the other materials
      (P < 0.05). However, following ball-milling the mean bond strength for Right-on
      was apparently significantly higher than that of the other materials. (P < 0.05).
      In this study, the mode of bond failure is also analysed and the use of Weibull
      analysis in bond strength testing is described.

PMID- 8580098
TI  - Ex vivo shear bond strength of fibreglass reinforced aesthetic brackets.
AB  - Fibreglass reinforced brackets (FGBs) and ceramic brackets were bonded to the
      enamel of extracted premolars to evaluate their shear bond strength and fracture
      mode. One-hundred extracted premolars were divided into five groups, and
      combinations of two-paste and no-mix composite, and plastic bracket conditioner
      were used in the test groups. Bond strength testing was carried out 24 hours
      after direct bonding. The shear strength of ceramic brackets with a two-paste
      composite was significantly higher than FGBs bonded with either two-mix or no-mix
      composite ( P < 0.05). Ceramic brackets bonded with two-mix and no-mix composite
      demonstrated a 30 and a 10 percent enamel fracture rate, respectively. There were
      no enamel or bracket fractures in any of the FGB groups.

PMID- 8580099
TI  - Adult orthodontics--a review.
AB  - The increased demand for orthodontic treatment by adults suggests a review of the
      literature might be timely. In this review we explore whether the increased in
      demand is real and matched by need. We also examine the reasons for treatment
      being sought and special considerations which are important during orthodontic
      treatment. Finally, we compare the orthodontic experience of adults and
      adolescents. We conclude that adults seeking treatment can be excellent patients
      with high motivation and co-operation. The limitations of orthodontic treatment
      must be explained at the beginning of treatment since adult expectations of
      orthodontics can be very high.

PMID- 8580100
TI  - Developmental changes in alignment of the lower labial segment.
AB  - The purpose of this study was to examine changes in lower incisor alignment at
      various developmental stages, from the time of eruption to the established
      permanent dentition and to try to predict the degree of crowding in the permanent
      dentition from that observed at earlier developmental stages. Forty-eight
      subjects (20 male, 28 female) with intact mandibular arches were selected from
      the Belfast growth study records. The lower incisor space condition was measured
      at each of four developmental stages: (1) initial eruption of the lower permanent
      incisors; (2) initial eruption of the permanent canines; (3) initial eruption of
      the second molars; (4) 3 years after eruption of the second molars. Differences
      in lower incisor space condition between each developmental stage were
      investigated and correlation analyses between the space conditions at each stage
      were carried out. On average, crowding of the lower incisors decreased to a
      statistically significant degree (- 0.9 mm) between stages 1 and 2, and increased
      between stages 3 and 4 (0.4 mm). Significant correlation coefficients between
      space condition at each developmental stage were found, but were considered
      unreliable as predictors of lower incisor crowding in the mature dentition.

PMID- 8580102
TI  - Pitfalls in orthodontic health service research.
AB  - With the increasing interest in the field of orthodontic health service and
      related research, this paper reviews some of the factors that should be
      considered when planning such research.

PMID- 8580101
TI  - A comparison of consecutive orthodontic referrals seen by a consultant unit and
      specialist orthodontic practitioners.
AB  - It has been suggested that the consultant orthodontic service and specialist
      practitioner service should have different roles, with the former concentrating
      its treatment input on the management of severe malocclusions. In an attempt to
      determine whether referring dental practitioners appeared to be aware of these
      differences, 100 consecutive orthodontic referrals seen at a consultant
      orthodontist's clinic were compared and contrasted with the same number seen at
      each of four specialist orthodontic practices located in the same city, and
      within 4 miles of the consultant unit. Comparisons were made both on the basis of
      clinical information obtained from study models and from analysis of referral
      letters. The consultant sample contained a greater proportion of requests for
      treatment plans, but there were few differences in terms of the range and
      severity of the actual malocclusions referred to each of these specialist
      services. The implications of these findings are discussed in relation to
      possible future developments of orthodontic services in the U.K.

PMID- 8580103
TI  - A combined obturator and expansion appliance for use in patients with patent oral
      nasal fistula.
AB  - A combined obturator and expansion appliance design is described for use in
      patients with patent oronasal fistulae. This is helpful in cleft palate cases,
      where small fistulae may increase in size during orthodontic expansion of the
      upper arch, resulting in increased hypernasality of speech and nasal escape.

PMID- 8580104
TI  - Functional appliance therapy in conjunction with growth hormone treatment. A case
      report.

PMID- 8580105
TI  - 'Keeping the saucers spinning'.

PMID- 8580106
TI  - What next?

PMID- 8580107
TI  - Superelastic nickel titanium coil springs.

PMID- 8580108
TI  - Retirement from orthodontic practice.
AB  - Retirement from orthodontic practice is discussed from the financial, practice,
      home, and personal aspects. The paper is a guide to planning for retirement and
      includes a list of the various agencies that should be contacted at the
      appropriate time. The recent changes made to the National Health Service Pension
      Scheme are outlined together with the various methods for disposal of the
      practice.

PMID- 8580109
TI  - Orthodontic facebow injuries.

PMID- 8580110
TI  - Orthodontic facebow injuries.

PMID- 8580111
TI  - Orthodontics in Germany. Recent changes to the remunerative system.

PMID- 8580112
TI  - BJO directory of orthodontic organisations.

PMID- 8580113
TI  - Repeat neurobehavioral study of borderline personality disorder.
AB  - Previous research has tentatively identified a large subgroup of patients with
      borderline personality disorder (BPD) with histories of developmental or acquired
      brain insults. Similarly, these studies have demonstrated a possible biological
      correlation between the severity of BPD and the number of previous brain insults.
      The possibility of frontal system cognitive dysfunction in BPD has been raised.
      This single-blind, case-control study of BPD showed that 13 of 24 subjects with
      BPD had suffered a brain insult. Correlations between neurodevelopmental/acquired
      brain injury score and the diagnostic interview for borderline (DIB) score (r =
      0.47), and between frontal system cognitive functioning and DIB score (r = -0.37)
      were seen. Neurocognitive testing and comparison with a cohort of subjects with
      traumatic brain injury (TBI) showed a pattern of similar cognitive functioning
      between the 2 groups, with the only differences on individual tests being in the
      direction of worse functioning in the group with BPD on 2 tasks. These results
      support the hypotheses described above. The main limitation reflects the low
      numbers of subjects.

PMID- 8580114
TI  - Ocular motor responses to unpredictable and predictable smooth pursuit stimuli
      among patients with obsessive-compulsive disorder.
AB  - This study was conducted to evaluate the smooth pursuit system functioning of
      patients with obsessive-compulsive disorder (OCD). For Study 1, 12 subjects with
      OCD and 12 nonpsychiatric subjects were administered 9-deg-per-sec ramp stimuli
      to elicit smooth pursuit eye movements. Consistent with a previous report,
      patients with OCD did not significantly differ from nonpsychiatric subjects on
      pursuit gain, or frequency of corrective and intrusive saccades. Patients with
      OCD, however, had smaller catch-up saccades during smooth pursuit than
      nonpsychiatric subjects. For Study 2, 12 subjects with OCD and 12 nonpsychiatric
      subjects were administered 2 different triangle wave stimuli with target
      velocities of 12 (0.2 Hz) deg per sec and 24 (0.4 Hz) deg per sec. Subjects with
      OCD and nonpsychiatric subjects did not significantly differ on any variable in
      the slow target velocity condition. When following 24-deg-per-sec targets,
      however, patients with OCD had significantly lower pursuit gain than the
      nonpsychiatric subjects. Results from Study 1 and 2 are consistent with the
      hypothesis that patients with OCD have a modest smooth pursuit deficit that is
      elicited only while following faster velocity targets.

PMID- 8580115
TI  - A neurochemical basis for the antipsychotic activity of loxapine: interactions
      with dopamine D1, D2, D4 and serotonin 5-HT2 receptor subtypes.
AB  - Loxapine is a typical neuroleptic that shows great structural and functional
      homology to the atypical antipsychotic clozapine. Chronic loxapine treatment is
      usually associated with extrapyramidal symptoms (EPS), whereas clozapine
      treatment is not. Conversely, loxapine does not produce the agranulocytosis that
      often results from protracted clozapine treatment. Earlier studies of loxapine
      have usually implicated D2 receptor blockade as the cause of the tardive
      dyskinesia that occurs with chronic treatment. More recently, loxapine's ability
      to potentiate serotonergic neurotransmission has also been implicated. In this
      study, the pharmacological affinities of loxapine for the dopamine D1, D2, D4, as
      well as serotonin-2 (5-HT2) and NMDA receptor subtypes, were investigated through
      direct radioreceptor assays. The findings indicate that loxapine displays an
      extremely strong binding affinity for dopamine D4 and serotonin 5-HT2 receptors,
      which suggests that both serotonergic and dopaminergic mechanisms contribute to
      the antipsychotic drug action and EPS associated with loxapine in the treatment
      of schizophrenia.

PMID- 8580117
TI  - Tc-99m HMPAO brain SPECT scanning in Munchausen syndrome.
AB  - Regional cerebral blood flow was studied in a patient with Munchausen syndrome
      using high resolution Tc-99m HMPAO SPECT. The scan demonstrated marked
      hyperperfusion of the right hemithalamus. The cranial CT scan was normal. The
      abnormal right hemithalamic blood flow is discussed in relation to the
      hypothesized neuropathy of this disorder.

PMID- 8580118
TI  - Repetitive behavior and repetition avoidance: the role of the right hemisphere.
AB  - Based on clinical observations of patients suffering from brain damage, a recent
      model assumes a right hemisphere dominance for the suppression of repetitive
      behavior. This study set out to test whether or not the well-known effect of
      repetition avoidance in sequential response production is likewise mediated by
      the right hemisphere. It was found that, in 40 healthy subjects, avoidance of
      repetitions in a random number-generation task correlated positively with a
      relative superiority for design as compared to letter fluency. Since design
      fluency is predominantly mediated by the right frontal lobe and letter fluency by
      the left, this finding supports the notion of a right hemisphere dominance for
      the avoidance of repetitive responses. This study illustrates the usefulness of a
      neurobehavioral approach to repetition behavior in the randomization of response.
      In particular, it demonstrates that the phenomenon of repetition avoidance may be
      better accounted for in terms of a control mechanism preventing perservation than
      by referring to human subjects' "generally biased concept of randomness."

PMID- 8580119
TI  - Apparent absence of famotidine-antipsychotic drug interactions in patients with
      chronic schizophrenia.

PMID- 8580116
TI  - Eating disorder and obsessive-compulsive disorder: neurochemical and
      phenomenological commonalities.
AB  - This paper explores a possible connection between neurochemistry and cognitions
      in eating disorders (ED). Cognitions play an important role in ED. However, a
      possible neurochemical origin of these cognitions has not been explored.
      Obsessive-compulsive disorder (OCD) is known as a disorder of thinking. Extensive
      neurochemical research conducted on this disorder indicates a connection between
      serotonin (5-HT) dysregulation and cognitions in OCD. This study used research
      done on OCD as a template to interpret the available research findings in ED and
      their possible meaning in terms of neurochemical origin of cognitions in ED. This
      paper suggests that the neurochemical and behavioral expression of both ED and
      OCD occur on a continuum. At one end of the continuum, ED and OCD are expressed
      through constrained behaviors of an avoidant quality. This pole is also
      characterized by high levels of serotonin markers. At the other end, both
      disorders are characterized by disinhibited approach behavior. This end of the
      continuum is characterized by low levels of 5-HT markers. It is suggested that
      these levels of 5-HT generate cognitions that may in turn promote specific
      behaviors.

PMID- 8580120
TI  - New perspectives on the eating disorders.

PMID- 8580121
TI  - Bulimia and anorexia nervosa in winter depression: lifetime rates in a clinical
      sample.
AB  - Symptoms of an eating disorder (hyperphagia, carbohydrate craving, and weight
      gain) are characteristic of wintertime depression. Recent findings suggest that
      the severity of bulimia nervosa peaks during fall and winter months, and that
      persons with this disorder respond to treatment with bright artificial light.
      However, the rates of eating disorders among patients presenting for the
      treatment of winter depression are unknown. This study was undertaken to
      determine these rates among 47 patients meeting the DSM-III-R criteria for major
      depression with a seasonal pattern. All were evaluated using standard clinical
      interviews and the Structured Clinical Interview for DSM-III-R. Twelve (25.5%)
      patients met the DSM-III-R criteria for an eating disorder. Eleven patients had
      onset of mood disorder during childhood or adolescence. The eating disorder
      followed the onset of the mood disorder. Clinicians should inquire about current
      and past symptoms of eating disorders when evaluating patients with winter
      depression.

PMID- 8580122
TI  - Protecting adolescents from hepatitis B infection.

PMID- 8580123
TI  - Critical issues surrounding hepatitis B vaccination for adolescents: a
      roundtable.

PMID- 8580124
TI  - Hepatitis B immunization in adolescents.
AB  - This article reviews the epidemiology of hepatitis B in the United States,
      previous vaccination strategy, and reasons for its failure and issues leading to
      the recommendation to vaccinate all adolescents. A review of specific hepatitis B
      virus risk behaviors of adolescents and barriers to vaccinating adolescents is
      covered. Strategies that favor successful completion of the immunization series
      are also examined. Hepatitis B infection is an important public health concern
      for adolescents. The previous vaccine strategy to immunize only individuals
      though to be at high risk was unsuccessful, especially because providers of care
      could not identify these individuals. Furthermore, many individuals thought not
      to be at high risk for infection were exposed through contacts which could not be
      identified. Challenges to immunization of adolescents include logistical issues,
      patient education, cost of the vaccine, and patient compliance. Several of these
      issues can be addressed by a school-based hepatitis B immunization program. The
      body of evidence and national policy is rapidly changing to support the
      recommendation that all adolescents receive the hepatitis B immunization series.
      The series would be most effective if administered during the middle-school
      years. A universal adolescent hepatitis B vaccination program would result in the
      most immediate health benefits and acceleration toward the eradication of
      hepatitis B in the United States.

PMID- 8580125
TI  - A hepatitis B vaccination program targeting adolescents.
AB  - PURPOSE: To determine the effectiveness of using a middle school for hepatitis B
      vaccination of adolescents. METHODS: An immunization program was designed to
      educate parents and students about hepatitis B virus (HBV) infection and
      hepatitis B vaccination using science class presentations and mailings. Students
      were given at each visit and on vaccination series completion. Costs were
      calculated and divided by the number of students completing the series to obtain
      per student cost. RESULTS: Of the 654 students, 519 (79%) received at least one
      dose of hepatitis B vaccine, 497 (76%) two doses, and 425 (65%) three doses.
      Student participation did not vary by grade level, gender, or income. Per student
      vaccination cost was $77.23 for those receiving three doses of hepatitis B
      vaccine and $66.04 when those receiving at least two doses were included. Of 103
      students with postvaccination serologic testing, three had evidence of previous
      hepatitis B virus infection, four had no evidence of vaccine induced immunity,
      and 96 (96% of susceptible students) developed protective levels of antibodies
      against hepatitis B surface antigen. The geometric mean antibody titer among
      persons responding to vaccination was 661 mIU. CONCLUSION: Hepatitis B
      vaccination of adolescents can be successfully integrated into a middle school
      setting.

PMID- 8580126
TI  - Hepatitis B vaccine acceptance among adolescents and their parents.
AB  - PURPOSE: To employ theoretic health decision models to determine strategies that
      may facilitate acceptance of hepatitis vaccination programs among adolescents and
      their parents/guardians. METHODS: The research was conducted in a hospital-based
      adolescent clinic between January and September 1994. Eighty adolescents and 65
      parents participated in a survey that was administered to new patients. Two
      groups (those who accepted the vaccine and those who rejected it) were compared
      for each variable and potential predictor. RESULTS: The majority of adolescents
      and parents indicated that their clinic care provider was the initial contact to
      initiate discussion about the vaccine. Significant predictors for parents'
      acceptance of the vaccination were their perceptions of the vaccine's importance
      to the care provider and concern about the general risk of the disease.
      Predictors for adolescents' acceptance of the vaccine was their perception that
      their parents felt it was important and the extent to which they believed it was
      for "everyone" to be vaccinated. CONCLUSIONS: Providers should be aware that
      adolescents are influenced by their parent's opinions and that the care
      provider's endorsement of the vaccine may be a key factor in parental acceptance
      of the vaccine. Results of this study have potential implications for public
      health approaches to facilitate vaccine acceptance.

PMID- 8580127
TI  - Position statement on hepatitis B immunization. Society for Adolescent Medicine.

PMID- 8580128
TI  - [Quality criteria in diagnostic radiology, goals and reality].
AB  - Quality criteria describe the medical standards (guidelines) with respect to the
      different aspects of radiological diagnosis. The indication does not seem to be
      justified in 20-50% of studies. Indication lists should be developed. Image
      quality has generally improved--with the exclusion of barium studies of the
      gastrointestinal tract. In 60% of patient studies, radiation exposure has been
      lowered to 25% due to the use of low-dose film-screen systems (speed class 400),
      higher exposure voltages, and improved constancy of the technical equipment. Over
      the last years diagnostically valuable computed tomography studies have been
      performed with considerably higher organs and effective doses. Technical
      restrictions in this field are necessary without compromising the diagnostic
      information. The benefit-risk ratio underscores the fact that the diagnostic and
      therapeutic benefit for the patient exceeds the nominal stochastic radiation risk
      by several orders of magnitude.

PMID- 8580129
TI  - [Quality assurance in neuroradiology].
AB  - Due to growing economic pressure, quality management in medicine has to be
      performed under the aspect of rationing and rationalization simultaneously. High
      quality and cost effectiveness in medicine, however, can only be achieved by
      institutions with an adequate quality of structure, procedure and outcome. While
      the technical criteria of the quality of structure can easily be measured, the
      assessment of the quality of the performance and the outcome are much more
      difficult so establish. Therefore standards of quality for the various diagnostic
      and interventional subspecialties of Neuroradiology have to be designed. The same
      is true for the evaluation of the quality assurance. The quality of
      neuroradiology has reached a comparatively high level simply because of the
      specialization compared to general radiology. This advantage should be utilized
      more often when major diagnostic departments are to be installed, particularly
      under the aspect of cost effectiveness plus high quality medicine.

PMID- 8580130
TI  - [Technique and economics of first worldwide roentgen conference via public phone
      lines with the Medical Desktop-Conference and Integrated Services Digital
      Network].
AB  - The introduction of the world's first Medical Desktop-Conference via public phone
      lines (ISDN-S2M) in spring 1994 for the weekly discussion of radiological
      findings with 25 orthopedic surgeons has proved the effectiveness of this system
      developed by the project BERMED. The use of standard hard- and software as well
      as ISDN are the most important factors to keep the system costs low. Technical
      advantages can be seen in the immediate, loss-free transmission of image and
      other patient-related data and in the integration of digital archives. Medical
      advantages are the 24-hour-availability of the radiologist and quality-control of
      the radiologists work. Practitioners and external hospitals can be tied closely
      to radiological service centers by using ISDNetwork.

PMID- 8580131
TI  - [Diagnostic results of abdominal computerized tomography in HIV-infected
      patients].
AB  - The exact frequency of pathologic findings in abdominal computed tomograms of HIV
      infected patients is not yet known. To analyse such findings, CT scans of 339 HIV
      infected patients were reviewed. While over four fifths of patients displayed
      abnormal findings; hepatosplenomegaly, lymphadenopathy, pathologically enlarged
      lymph nodes, and bowel wall thickening were the most common signs of disease.
      Only for enlarged lymph nodes could a dependency on clinical stage of the
      infection be demonstrated. As a conclusion, abdominal computed tomography reveals
      pathologic findings in the vast majority of HIV-infected patients, almost
      independent of clinical stage. Specifically, CT provides well documented lymph
      node staging. There are practically no age-or sex-dependent disease patterns in
      abdominal CT scans.

PMID- 8580132
TI  - [Vena cava invasion in adrenal gland tumors: findings in nuclear magnetic
      resonance tomography].
AB  - In rare cases, large adrenal masses with a suspicion of malignancy exhibit tumor
      extension into the adrenal vein and inferior vena cava. When planning surgery,
      the relationship of the extension to the inferior vena cava is of decisive
      importance. We describe in two cases on the detection of a tumor thrombus in the
      inferior vena cava arising from a malignant adrenal mass by means of MR
      angiography (TOF, coronary 2D GRE images [FLASH], 3 slices acquired during 15
      second apnea). The angiograms correlated well with the results of DSA
      venacavography and with the intraoperative findings. Thus, MRA has been
      demonstrated to be suitable for the certain proof of a venous tumor thrombus not
      only in cases of renal cell carcinomas but also in cases of malignant adrenal
      masses. The method should be applied whenever there is evidence of a venous
      involvement in the adrenal MR images.

PMID- 8580133
TI  - [Incomplete Boerhaave syndrome of the cervical esophagus].
AB  - It is known that an acute postemetic injury may evoke a spontaneous rupture of
      the oesophagus. This spontaneous rupture may produce an intramural hematoma or a
      laceration of the oesophagus wall. The intramural hematoma is restricted to the
      esophageal wall and may produce a fistula into the lumen of the oesophagus (with
      creation of a double lumen) or into the mediastinum (haematoma of the
      mediastinum). On the other hand the rupture may extend from the mucosa (lesion of
      Mallory-Weiss) into the complete wall of the oesophagus (Boerhaave's Syndrome).
      There are reports on a lesion of the exterior muscular layer of the third distal
      half of the oesophagus, which had evoked an acute haemorrhage into the
      mediastinum and has been defined as a variant of Boerhaave's syndrome. We now
      describe a similar case which is confined to the cervical oesophagus and has been
      treated without surgical intervention.

PMID- 8580134
TI  - [Space-occupying lesions of the lacrimal gland in CT and MRI exemplified by 4
      cases].
AB  - In an extended case report, we discuss four cases with masses in the lacrimal
      fossa representing the most important entities in this region (lymphoma,
      pleomorphadenoma, inflammatory pseudotumor, and malignant epithelial tumor). The
      different indications for CT and MRI are explained. For the differential
      diagnosis of lacrimal gland lesions, the following imaging parameters are
      important: the shape of the lacrimal gland, the inner structure, the degree of
      contrast enhancement, and the surrounding bony structures. In the evaluation of
      the expansion of lacrimal gland lesions, CT in thin slices with multiplanar
      reconstructions is equal to MRI. However, the contrast-enhancement of lacrimal
      glands is better evaluated with MRI than with CT. The bony structures are better
      visualized on CT than on MRI.

PMID- 8580135
TI  - [Clinical aspects and diagnosis of jejunal diverticulosis].
AB  - Jejunal diverticulosis consists of multiple acquired jejunal herniations of the
      mucosa and submucosa with an incidence of 1.3 to 2.3%. Clinical symptoms are
      rare. Numerous and large diverticulae, however, can cause severe abdominal
      complaints. Etiologically factors always consist of a motility disorder with
      bacterial overgrowth and rise of intraluminal pressure. An enteroclysis helps to
      determine the diagnosis. Plain x-rays and a CT of the abdomen are other helpful
      radiological tools.

PMID- 8580136
TI  - [Manifestation of pneumothorax 7 days after port implantation. Report of a single
      case].
AB  - The subcutaneous implanted venous port device offers a safe central venous access
      and allows for ambulatory treatment. This case report describes a late
      manifestation of a pneumothorax after venous port implantation which, in fact, is
      a rare but significant complications. The lack of a correlation of the signs and
      symptoms with the interventional procedure may lead to inadequate or delayed
      treatment. The immediate postprocedural X-ray can be false negative when air
      leaks into the pleural cavity very slowly. Therefore both patients and referring
      physicians should be informed about the possibility of the late manifestation of
      a pneumothorax.

PMID- 8580137
TI  - [Atypical focal fatty liver].
AB  - Focal fatty liver disease can cause difficulties in the differential diagnosis by
      ultrasound, CT, and MRI. This case report describes the atypical findings of
      focal spared areas of fatty liver disease in association with inflammatory
      changes, which were thought to be malignant focal liver lesions.

PMID- 8580138
TI  - [Radiologic image of massive diverticulosis of the small intestine].
AB  - Diverticulosis of the small bowel is rare compared with diverticular disease of
      the colon. Diverticulosis of the duodenum is more common than the involvement of
      the whole small bowel including the ileum which is a very rare condition. In a
      patient presenting with gastrointestinal bleeding extensive diverticulosis of the
      whole small bowel was identified; the etiology is discussed.

PMID- 8580139
TI  - [Safety aspects in MR imaging].
AB  - With the growing number of Magnetic Resonance Systems in operation in clinical
      practice, safety aspects gain increasing importance. Therefore, it is necessary
      to evaluate possible risks and effects on human health. After an introduction to
      the basic principles and techniques involved, the various effects on biological
      systems and especially the human organism caused by the static magnetic field,
      the alternating magnetic fields and the high frequency fields required are
      described on the basis of current literature and partially also on our own
      experience. Basic information for the safe operation of diagnostic Magnetic
      Resonance Systems is presented. Limits for exposure to magnetic fields and time
      dependent changes of electromagnetic fields for patients and employees as
      suggested by health authorities are given.

PMID- 8580140
TI  - [Reducing radiation exposure in angiography].
AB  - Interventional procedures in angiography result in an increased radiation
      exposure for the physician, medical personnel, and the patient longer
      fluoroscopic times and of images as compared with pure diagnostic examinations.
      Damages like epilation and erythema are potential effects. Measures are proposed
      in this paper to reduce the radiation exposure. There are technical means and
      possibilities in the application technique. Quality checks and remote diagnosis
      support these measures in addition by assuring a continuous image quality.

PMID- 8580141
TI  - [High intensification film-screen systems in thoracic diagnosis. A clinical
      comparative study].
AB  - OBJECTIVE: The quality of chest images was evaluated for a conventional screen
      film system, a new asymmetric screen-film system, and a new uv screen-film
      system. MATERIALS AND METHODS: 138 chest radiographs (69 p.a., 69 lateral)
      obtained with three different high intensification screen-film combinations were
      compared. Film density and film contrast were measured. Three readers graded the
      image quality according to 16 criteria. RESULTS: The asymmetric film-screen
      combination Insight HC showed the lowest film contrast, the best exposure range,
      and a elevated film density in the mediastinal area. The asymmetric screen-film
      system was ranked by all three observers as being substantially better in image
      quality. CONCLUSION: Compared to conventional screen-film systems, the new screen
      film systems can improve the image quality of chest radiographs. Therefore, the
      new high intensification screen-film combinations can be used as a low cost
      alternative to the Amber technique and digital radiography.

PMID- 8580142
TI  - [An improved method for determining the mean parenchyma dose in mammography].
AB  - In mammography, it is currently assumed that the mean dose to glandular tissue DG
      is relevant to characterize the risk of carcinogenesis. The mean glandular dose
      DG results from the measured air kerma Ka at the location of the entrance surface
      of the breast multiplied by the conversion factors g, which usually are
      calculated with the help of Monte-Carlo-Simulations and which are mostly given
      for a standard composition of tissue (50% glandular/50% adipose tissue). By means
      of the signals of the double-detector of the automatic-exposure-control of the
      mammographic device, it is possible to obtain information about the mean
      composition of the breast-tissue. The knowledge of this composition enables a
      better calculation of the mean glandular dose DG by using conversion factors that
      are adapted to the tissue. This method was applied to a total of 1020 women. The
      comparison with the evaluation by using the conventional method shows, on
      average, deviations in the mean glandular dose of 9%, in specific cases the
      differences can be as much as 35%.

PMID- 8580143
TI  - [Evaluation of cassettes for uniformity and reliability of the enhancement
      factor].

PMID- 8580144
TI  - Second-order derivative spectrophotometric assay for imipramine hydrochloride and
      diazepam in pure admixtures and in dosage forms.
AB  - The determination of imipramine HCl and diazepam in tablets by derivative
      spectrophotometry is described. The drugs in combined preparations have been
      quantified using the second-order derivative spectra of their solutions in 0.1 M
      HCl. The method has been applied to pure drug mixtures as well as commercial
      preparations and was found to be precise and reproducible. Compliance of Beer's
      Law was observed in the concentration range of 10-70 micrograms ml-1 for
      imipramine HCl and 2-8 micrograms ml-1 for diazepam. Lower limits of detection at
      the 95% confidence level were 1.96 micrograms ml-1 for imipramine HCl and 0.21
      microgram ml-1 for diazepam.

PMID- 8580145
TI  - An investigation of the use of nile red as a long-wavelength fluorescent probe
      for the study of alpha 1-acid glycoprotein-drug interactions.
AB  - Spectrofluorimetry in the long-wavelength region of the electromagnetic spectrum
      (600-1000 nm) is a fairly recent development in photoluminescence spectroscopy,
      which has numerous advantages over measurements in the more conventional
      ultraviolet and visible spectral region. 9-Diethylamino-5H-benzophenoxazine-5-one
      (Nile Red) is an unchanged, hydrophobic molecule, and long-wavelength
      fluorescence of which is strongly influenced by the polarity of its environment.
      When Nile Red was added to solutions of alpha 1-acid glycoprotein (Orosomucoid.
      OMD), it showed an enhancement in fluorescence intensity and a shift to blue in
      emission wavelength, suggesting it was binding hydrophobically to a non-polar
      site on the protein. The association constant (12,261,000 +/- 900,000 M-1) and
      number of binding sites (0.746 +/- 0.044) were calculated for the probe. Upon
      addition of both acidic and basic drugs, the Nile Red fluorescence reverted to
      its unbound form, indicating that OMD probably has one high-affinity, wide and
      flexible binding area for such drugs. Possible enantiomeric selectivity was shown
      with ephedrine, and the association constant determined for a racemic mixture of
      propranolol was found to be comparable to other values obtained with alternative,
      more conventional techniques.

PMID- 8580146
TI  - Micellar-enhanced synchronous-derivative fluorescence determination of
      derivatized folic acid in pharmaceutical preparations.
AB  - A sensitive and inexpensive micellar-enhanced synchronous-derivative
      spectrofluorimetric method is described for the determination of folic acid in
      pharmaceutical preparations. The method is based upon derivatization of the
      vitamin with fluorescamine in acid solution and enhancement of the fluorescence
      with a surfactant. Linear fluorimetric analytical curves were obtained for folic
      acid concentrations of 0.05-6 micrograms ml-1 (detection limit 0.012 micrograms
      ml-1); the RSD for 1 micrograms ml-1 of folic acid was 2.82%. The method has been
      applied to the determination of folic acid synthetic mixtures and pharmaceutical
      preparations.

PMID- 8580147
TI  - A radiometric TLC assay of liver microsomal dextromethorphan O-demethylation.
AB  - A simple and sensitive assay for in vitro analysis of dextromethorphan O
      demethylation, a marker for P450 2D deficiency in both humans (2D6) and rats
      (2D1), has been devised. Commercially available [N-methyl-3H]-dextromethorphan
      was used to develop a radiometric TLC assay for dextromethorphan O-demethylation.
      Hexane-triethylamine efficiently extracted dextromethorphan and metabolites from
      rat liver microsomes, and a solvent system of cyclohexane-toluene-diethylamine
      (65:15:20, v/v/v) provided sufficient separation (approximately 2 cm) between the
      two radioactive bands, dextromethorphan and dextrorphan, and no interference from
      the unlabeled N-demethylation products, 3-methoxymorphinan and 3
      hydroxymorphinan. The recovery of dextrorphan from TLC plates increases with
      microsomal protein and incubation time. An eight-fold decrease in activity was
      noted in female Dark Agouti relative to the male Sprague-Dawley rats, respective
      models for poor and extensive P450 2D metabolizers. The assay, even with an
      approximately 100-fold dilution of radiolabeled substrate, had an approximate
      limit of detection of 100 pmol. Within- and between-run imprecision was 12.4% and
      7.2%, respectively. The radiometric TLC assay for dextromethorphan O
      demethylation was sensitive and easy, and used readily available equipment.

PMID- 8580148
TI  - Assay of paracetamol and its metabolites in urine, plasma and saliva of children
      with chronic liver disease.
AB  - A high-performance liquid chromatographic (HPLC) assay of paracetamol and its
      metabolites is described. The method for quantifying the metabolism of
      paracetamol in children with chronic liver disease and the good correlation
      between plasma and salivary concentrations of paracetamol is demonstrated.
      Despite an increasing bias between the two methods with increasing concentration
      of paracetamol, it is concluded that salivary assay is satisfactory for
      characterising paracetamol pharmacokinetics in the group of patients studied.

PMID- 8580149
TI  - Disposition of human drug preparations in the horse. IV. Orally administered
      fenoprofen.
AB  - Plasma and urinary concentrations of the non-steroidal anti-inflammatory drug
      fenoprofen were determined by a high-performance liquid chromatographic procedure
      following oral administration of a dose of 3 g to fed and fasted horses. In
      plasma, fenoprofen was present in detectable concentrations for 6-12 h. Free
      access to hay significantly reduced the peak plasma concentration and
      bioavailability of fenoprofen, and large interindividual differences in
      absorption and elimination pattern occurred. In fasted horses, fenoprofen was
      rapidly absorbed with a mean half-life of 0.10 h. Maximum concentrations were
      found 0.63 +/- 0.21 h after dosing. The elimination half-life was 0.9 h. As early
      as 1 h after dosage, fenoprofen could be detected in hydrolysed and unhydrolysed
      urine, and remained detectable up to 48 h. The maximum excretion rate and peak
      concentration occurred 2 h after administration, irrespective of the feeding
      schedule. In fed horses, a second maximum occurred after 9 h. The percentage of
      the dose excreted as unchanged fenoprofen in 12 h was 13.0 +/- 6.8%. A recovery
      of 21.9 +/- 7.4% and 42.2 +/- 7.0% of the dose was obtained after enzymatic and
      alkaline hydrolysis, respectively. At least three hydroxylated metabolites were
      detected in hydrolysed urine.

PMID- 8580150
TI  - Rapid profiling of carbohydrate glycoforms in monoclonal antibodies using
      MALDI/TOF mass spectrometry.

PMID- 8580151
TI  - The determination of alendronate sodium in tablets by inductively coupled plasma
      (ICP).

PMID- 8580152
TI  - Determination of netilmicin in plasma by HPLC.

PMID- 8580153
TI  - The development and cross-validation of methods based on radioimmunoassay and
      LC/MS-MS for the quantification of the class III antiarrhythmic agent, MK-0499,
      in human plasma and urine.
AB  - An analytical method based on radioimmunoassay (RIA) has been developed for the
      determination of the antiarrhythmic agent, MK-0499, in plasma and urine. Owing to
      the potency of the drug, the specificity of this assay in human plasma could not
      be adequately determined using conventional RIA procedures. A highly specific
      procedure, based on LC/MS-MS, was developed to cross-validate the RIA. The lower
      quantifiable limits of the RIA and LC/MS-MS-based methods were 0.05 and 0.013 ng
      ml-1, respectively. Cross-validation data, compared using paired student's t-test
      regression analysis, showed excellent correlation between methods. The mass
      spectrometric assay was also used to simultaneously measure plasma concentrations
      of unlabeled and 14C-labeled MK-0499 following administration of the drug at high
      specific activity to volunteers.

PMID- 8580154
TI  - Validated capillary electrophoresis method for the assay of a range of basic
      drugs.
AB  - A capillary electrophoresis method has been developed and validated for the
      analysis of a wide range of basic drugs. Acceptable precision was obtained by
      employing an internal standard. Optimal sensitivity was obtained using low UV
      wavelengths. An experimentally designed study showed the method to be robust. The
      method has advantages over HPLC in terms of simplicity, speed and cost. The
      method is now in routine use for identity confirmation and assay of both drug
      substance and formulations.

PMID- 8580155
TI  - Daily validation procedure of chromatographic assay using gaussoexponential
      modelling.
AB  - High performance liquid chromatography is one of the most successful analytical
      methods used for the quantitative determination of drugs in biological samples.
      However, this method is marked by a lack of performance reproducibility:
      chromatographic peaks become wider and even asymmetrical as the column ages.
      These progressive changes in the chromatographic parameters have to be taken into
      account when evaluating the validation criteria for the method. These criteria
      change with the ageing process of the column leading to the need for new
      estimations to assure the quality of the results. Procedures are proposed for the
      daily determination of some validation criteria using the exponentially modified
      Gaussian (EMG) model of the chromatographic peak. This modelling has been studied
      on simulated chromatographic peaks in order to obtain the relationships between
      chromatographic measurements and EMG parameters.

PMID- 8580156
TI  - Assignment of the 750 MHz 1H NMR resonances from a mixture of transacylated ester
      glucuronic acid conjugates with the aid of oversampling and digital filtering
      during acquisition.
AB  - Many drugs containing carboxylic acid functional groups are metabolised in vivo
      to ester glucuronides (1-O-acyl-beta-D-glucopyranuronates) and, of these, a
      number show a propensity to undergo internal isomerisation via a transacylation
      process, causing the carboxylic acid moiety to migrate successively to the 2-, 3-
      and 4-positions of the glucuronic acid. These products may be responsible,
      through reactions with plasma proteins, for some of the allergenic side effects
      in a number of non-steroidal anti-inflammatory drugs. It is important to
      understand those properties of the drug molecules which facilitate this reaction,
      and to this end we have studied the transacylation product formation and reaction
      kinetics in a series of aryl carboxylic acid glucuronides using NMR spectroscopy.
      However, the resulting 1H NMR spectra are very complex with much resonance
      overlap, and recourse to spectral simplification processes is necessary. Here,
      improvement in spectral resolution by oversampling and digital filtering to
      restrict the detection range of the spectrometer, thus yielding improved digital
      resolution, is demonstrated. The approach has been applied to the assignment of a
      mixture of transacylated ester glucuronides of 2-trifluoromethylbenzoic acid
      through the use of a two-dimensional 1H-1H TOCSY experiment.

PMID- 8580157
TI  - Trace quantitation of the novel cholinesterase inhibitor in human plasma by
      capillary gas chromatography/ion trap mass spectrometry.
AB  - This paper demonstrates the utility of an ion trap mass spectrometer as a
      detector for trace quantitative determinations of pharmaceuticals in human plasma
      by capillary gas chromatography/mass spectrometry. A novel acetylcholinesterase
      inhibitor (CI-1002) was selected as an illustrative example for the technique.
      When coupled with a selective solid-phase extraction, this approach was capable
      of quantifying as little as 34 pg (0.50 ng ml-1, RSD = 12.7%) of compound on the
      column, and the inter-run precision was typically 3-4% RSD over a 0.5-25 ng ml-1
      linear range. The advantages and requirements of the technique, in addition to
      the prospects for improvements in the detection limit, are discussed.

PMID- 8580158
TI  - Degradation profile and identification of the major degradation products of
      dobupride under several conditions by GC/MS and HPLC-particle beam/MS.
AB  - The effect of pH, light, temperature and oxygen on the stability of dobupride
      (1), a novel gastroprokinetic drug, has been studied, storing the sample in the
      solid state and as a solution in methanol-water. The main forced degradation
      products have been identified by means of techniques such as GC/MS and HPLC
      particle beam/MS, and two major degradation pathways have been characterized. One
      degradation route involves the loss of chlorine, yielding 4-amino-2-butoxy-N-[1
      (1,3-dioxolan-2-ylmethyl)piperid -4-yl]benzamide (4) as the major degradation
      product. The second pathway results from cleavage of the piperidine-amide bond,
      producing 4-amino-2-butoxy-5-chlorobenzamide (2) as the major degradation
      product. Under the studied conditions, except when exposed to direct light in
      solution, dobupride has been shown to be very stable: after 5 months storage, the
      benzamide 2 (second pathway) was the only product identified (less than 0.5%).
      However, when dobupride in solution is exposed to natural or artificial sunlight,
      degradation is very fast, and after 7 days only 5% of the unchanged product
      remains. Under these circumstances, the main degradation route is the first one,
      with compound 4 being the most abundant degradation product, and compound 2 only
      being detectable in small amounts.

PMID- 8580159
TI  - Measurement of brimonidine concentrations in human plasma by a highly sensitive
      gas chromatography/mass spectrometric assay.
AB  - Brimonidine is an alpha 2-adrenergic agonist that is efficacious in lowering
      intraocular pressure in humans. A highly sensitive and selective gas
      chromatography/mass spectrometry (GC/MS) assay is described for quantitation of
      brimonidine in human plasma following ocular installation. Brimonidine in 1 ml of
      plasma was extracted together with tetradeuterated brimonidine (internal
      standard) and clonidine (carrier) by solvent extraction. After solvent
      evaporation, 3,5-bis(trifluoromethyl)benzoyl derivatives were formed and injected
      onto a GC/MS apparatus under negative chemical ionization conditions. The ions
      monitored for derivatized brimonidine and tetradeuterated brimonidine were m/z
      691 [M-HBr] and m/z 694 [M-DBr], respectively. Calibration curves were linear
      from 2 to 1000 pg ml-1 (r2 = 0.981-0.996). The method was specific for
      brimonidine relative to endogenous compounds in plasma. The inter-day relative
      standard deviation for analysis of quality controls was 12% or less, and the
      inter-day assay accuracy ranged from 97 to 104% of nominals. The GC/MS assay
      showed adequate sensitivity for analysis of human samples from volunteers
      ocularly dosed with 0.5% brimonidine tartrate solution. Overall, the GC/MS assay
      showed excellent precision and accuracy, and a minimum quantifiable concentration
      of 2 pg ml-1.

PMID- 8580160
TI  - Rotavirus shedding in feces of gnotobiotic calves orally inoculated with a
      commercial rotavirus-coronavirus vaccine.
AB  - The purpose of this study was to monitor by negative stain electron microscopy
      the shedding of rotavirus in the feces of gnotobiotic calves orally inoculated
      with a commercial modified live bovine rotavirus-bovine coronavirus vaccine.
      Negative stain electron microscopic examination detected vaccine rotavirus in
      only 1 of 41 daily fecal specimens collected from 3 gnotobiotic calves during the
      2 weeks following oral inoculation with a US Department of Agriculture-licensed
      modified live bovine rotavirus-bovine coronavirus vaccine. In contrast, rotavirus
      was demonstrable by the same negative stain electron microscopic examination
      procedure in 17 of 19 fecal specimens collected from diarrheic gnotobiotic or
      colostrum-deprived calves during the first 8 days after inoculation with virulent
      bovine rotavirus field strains. Rotavirus was also detected by this procedure in
      4 enzyme-linked immunosorbent assay positive fecal specimens collected from
      naturally-infected diarrheic dairy calves. These results suggest that fecal
      shedding of vaccine rotavirus demonstrable by electron microscopic examination is
      uncommon following oral inoculation of calves with the bovine rotavirus-bovine
      coronavirus vaccine.

PMID- 8580161
TI  - Comparison of detection methods for bovine viral diarrhea virus in bovine
      abortions and neonatal death.
AB  - The objective of this study was to examine a monoclonal antibody-based
      immunohistochemical staining method for its efficacy in diagnosis of bovine virus
      diarrhea virus (BVDV)-induced abortion and neonatal calf death. This method was
      compared to viral isolation and immunofluorescence staining of frozen tissue
      sections. Tissues from 105 cases, 53 fetuses and 52 neonates, were tested by the
      3 methods. There were significant numbers of both false negatives and false
      positives with the immunofluorescence method and significant numbers of false
      negatives with the viral isolation method. Of the methods tested,
      immunohistochemical staining using monoclonal antibody 15C5 performed best,
      differentiating 97% of positive and negative cases. These results indicated that
      immunohistochemical staining can be applied to improve the accuracy of BVDV
      diagnosis in cases of abortion and perinatal death.

PMID- 8580162
TI  - Genome analysis of North American small ruminant lentiviruses by polymerase chain
      reaction and restriction enzyme analysis.
AB  - The polymerase chain reaction (PCR) was used to amplify portions of the gag and
      env structural genes of 8 ovine and 1 caprine lentivirus isolates of North
      American origin. Three sets of primers were used to amplify p16, p25, and N'-gp40
      gene fragments, and 1 set, annealing highly conserved portions of long terminal
      repeat (LTR) among small ruminant lentiviruses, was used as a positive control.
      Variable PCR amplification efficiency was observed. Different stringency
      conditions of hybridization with specific DNA probes were used to maximize
      detection of the PCR product. The p25 primers detected all strains, the gp40
      primers detected 1 ovine and the caprine strain, and the p16 primers detected
      only 1 ovine isolate. All strains were detected by LTR primers. Restriction
      endonuclease analysis of 5 amplified p25 and 2 N'-gp40 gene fragments revealed
      extensive heterogeneity among these North American small ruminant lentiviruses.

PMID- 8580163
TI  - Development and application of an immunohistochemical staining technique to
      detect avian polyomaviral antigen in tissue sections.
AB  - An immunohistochemical staining technique was developed to detect polyomaviral
      antigens of budgerigar fledgling disease in formalin-fixed tissue sections. This
      technique used an indirect avidin-biotin, alkaline phosphatase labeling system
      with a mixture of monoclonal antibodies developed against the virus major capsid
      protein. The staining technique was applied retrospectively to 24 avian
      accessions which were originally diagnosed as budgerigar fledgling disease or
      avian polyomavirus infection based on microscopic findings including typical
      intranuclear inclusions. Immunohistochemical staining resulted in positive
      reactions in some tissues from 17 of 24 cases. The tissues most frequently
      containing typical intranuclear inclusions or positive immunohistochemical
      staining were the spleen, liver, and kidney. Neither of the 2 nonpsittacine cases
      was positive immunohistochemically. This technique may be used wither as a rapid
      test on routinely processed diagnostic samples to confirm the presence of avian
      polyomavirus or for pathogenesis research studies.

PMID- 8580164
TI  - Gastrointestinal and skin lesions in piglets naturally infected with pseudorabies
      virus.
AB  - Pseudorabies virus (PRV) infection was diagnosed in 4 piglets from a litter by
      immunohistopathologic examination and virus isolation. Three piglets had moderate
      to severe neuronal degeneration, and PRV antigen was detected in Auerbach's
      myenteric plexus and Meissner's submucosal plexus of the gastrointestinal tract.
      One piglet had 2 types of skin lesions. One lesion appeared on the hip and ear
      and was characterized by ballooning degeneration, necrosis of epithelial cells,
      and intranuclear inclusion bodies. The other was found on the ear and hematoma
      like lesion was composed of fibrinoid exudation and degenerative connective
      tissue. PRV antigen was clearly demonstrated in both skin lesions. These results
      suggested that degeneration of myenteric plexuses might be another characteristic
      of lesions in PRV-infected pigs and that the virus spreads by interaction between
      the skin and myenteric plexuses to the central nervous system.

PMID- 8580165
TI  - Persistence of porcine reproductive and respiratory syndrome virus in serum and
      semen of adult boars.
AB  - Four seronegative adult boars were intranasally inoculated with porcine
      reproductive and respiratory syndrome virus (PRRSV) isolate VR-2332. Serum and
      semen were collected 2-3 times weekly for over 100 days postinoculation (DPI).
      Serum samples were assayed for PRRSV by virus isolation (VI) and a polymerase
      chain reaction (PCR) and screened for antibodies to PRRSV using the indirect
      fluorescent antibody (IFA) and virus neutralization (VN) tests. Semen was assayed
      for PRRSV RNA by PCR. Virus and viral RNA was detected in the serum of all boars
      within 1 DPI by Vi and/or PCR. However, VI results indicated that viremia was
      transient and occurred from 1 to 9 DPI. Viral RNA was detected in serum from 1 to
      31 DPI. In the acute stage of the infection, PRRSV RNA was detected in serum by
      PCR prior to the presence of viral RNA in semen. The PRRSV RNA was detected in
      semen as early as 3 DPI and persisted for 25 DPI in 2 of the boars and 56 and 92
      DPI in the remaining 2 boars. Detection of PRRSV RNA in semen occurred 2-8 and 28
      35 days prior to the detection of antibodies by IFA and VN, respectively. PRRSV
      was isolated from the bulbourethral gland of the boar that shed viral RNA in
      semen for 92 DPI. These results suggest that PRRSV RNA can be detected by PCR in
      boar serum and semen, and may persist for variable periods of time. Viremia and
      the serologic status of the boar are not adequate indicators of when PRRSV or
      PRRSV RNA is being shed in the semen. Preliminary findings also indicated that
      neither shipping stress nor reinoculation with homologous PRRSV resulted in
      viremia or viral RNA shedding in semen.

PMID- 8580166
TI  - Detection of Anaplasma marginale DNA in bovine erythrocytes by slot-blot and in
      situ hybridization with a PCR-mediated digoxigenin-labeled DNA probe.
AB  - A 409-base pair (bp) DNA fragment derived from the msp-1 beta gene of Anaplasma
      marginale was amplified and simultaneously labeled with digoxigenin-11-dUTP by a
      polymerase chain reaction (PCR) assay. The resulting digoxigenin-labeled 409-bp
      PCR product was used as a probe for slot-blot and in situ hybridization to detect
      A. marginale DNA from experimentally infected bovine erythrocytes. The hybrid
      formation was detected with alkaline phosphatase-conjugated anti-digoxigenin
      antibody and substrates 5-bromo-4-chloro-3-indolyl phosphate and nitroblue
      tetrazolium salt. In slot-blot hybridizations, the probe detected A. marginale
      DNA from approximately 1,000-10,000 infected erythrocytes in 1.25 ml of whole
      blood, which is equivalent to a parasitemia level of 0.00001%. The probe proved
      to be a A. marginale-specific when tested with 17 species of microorganisms. The
      applicability of the probe for diagnosis was tested by screening A. marginale
      infections in 2 experimentally infected splenectomized cattle before
      microscopically detectable parasitemias and after acute infection. After
      inoculation of infected blood, A. marginale infections were detected with the
      probe 14 days prior to detection in stained smears. Microscopically inapparent
      parasitemias were also detected with the probe for 2 months after acute disease.
      When the probe was used for in situ hybridization on methanol-fixed blood smears,
      probe reaction could be visualized with light microscopy on A. marginale
      inclusions within infected erythrocytes. The probe reaction was not observed on
      leukocytes and uninfected erythrocytes from infected blood smears, on
      erythrocytes from uninfected blood samples, or on samples infected with A. ovis,
      Babesia bovis, or B. bigemina. This PCR-mediated nonradioactive probe appears to
      be a sensitive diagnostic test for A. marginale.

PMID- 8580167
TI  - Evaluation of an indirect ELISA for the diagnosis of bovine brucellosis.
AB  - Control and eradication of bovine brucellosis is usually based on the serological
      detection of antibodies. In Argentina, the rose bengal test (RB) and the buffered
      plate antigen test (BPA) are the 2 screening tests officially recognized, whereas
      the 2-mercaptoethanol test (2ME) and the tube agglutination test (SAT) are the
      confirmatory assays currently in use. In order to improve the serological
      diagnosis of bovine brucellosis in Patagonia, Argentina, an indirect enzyme
      linked immunosorbent assay (I-ELISA) kit distributed by the International Atomic
      Energy Agency was evaluated. Sera from negative nonvaccinated, negative but
      vaccinated, and positive animals were tested by all the above techniques. The
      specificity of the I-ELISA (98.9% and 97.2%) was similar to that of the BPA, RB,
      2ME and complement fixation (CF) tests when used to test sera from negative
      nonvaccinated and negative but vaccinated animals, respectively. The sensitivity
      of the I-ELISA (98.7%) was higher than the BPA test (96.1%) and the CF test
      (95.2%). The I-ELISA kit evaluated in this study was thought to be a valuable
      tool for the diagnosis of bovine brucellosis in the Patagonia region where little
      epidemiological information is available about this disease, and where large
      numbers of sera should be tested to obtain such information.

PMID- 8580168
TI  - Experimental reproduction of Haemophilus parasuis infection in swine: clinical,
      bacteriological, and morphologic findings.
AB  - Haemophilus parasuis is a common cause of polyserositis and polyarthritis in
      swine. Little is known about the mucosal and systemic sites of replication and
      lesions which follow an aerosol exposure to H. parasuis. In this experiment 5
      week-old cesarean-derived, colostrum-deprived (CDCD) pigs were inoculated
      intranasally with an inoculum containing 2 x 10(9) colony-forming units of H.
      parasuis. Two principals and one control pig were necropsied at 12, 36, 84, and
      108 hours postinoculation (PI) and samples obtained for bacteriologic culture and
      microscopic examination. Inoculated pigs developed clinical signs of inappetence,
      reluctance to move, lameness, and a serous nasal discharge. Macroscopic findings
      included a fibrinous polyserositis and polyarthritis 36 hours PI which became
      progressively more severe at 84 and 108 hours PI. No lung lesions were grossly
      visible. Microscopic lesions included a mild purulent rhinitis at each post
      inoculation interval and fibrinous to fibrinopurulent synovitis and serositis at
      36, 84, and 108 hours PI. A focal suppurative bronchopneumonia was observed in
      one pig examined at 36 hours PI. The nasal cavity and trachea were the only
      mucosal sites from which H. parasuis was reisolated. Haemophilus parasuis was
      isolated from the blood and systemic sites at 36, 84, and 108 hours PI. Findings
      presented indicated that intranasal inoculation of 5-week-old CDCD pigs with H.
      parasuis results in clinical signs and lesions of polyserositis and polyarthritis
      typical of field cases and is a useful model for the study of H. parasuis
      pathogenesis. The results also suggest that H. parasuis initially colonizes the
      nasal mucosa.

PMID- 8580169
TI  - Enzyme-linked immunosorbent assay for Salmonella serology using
      lipopolysaccharide antigen.
AB  - Enzyme-linked immunosorbent assay (ELISA) using Salmonella lipopolysaccharide
      (LPS) to measure specific IgG titers in cattle has proven useful. Serology can be
      used to assess vaccine responses and infection rates, to detect carriers, and to
      aid in epidemiologic studies. The objective of this study was to assess cross
      reactions using sera from cattle vaccinated with different Salmonella serogroups.
      ELISA plates using lipopolysaccharide from serogroup B, C1, C3, D1 or E1 as the
      plate antigens were tested. LPS was extracted from Salmonella typhimurium
      (Serogroup B; somatic antigens 01, 4, 12), S. montevideo (C1; 06, 7), S. kentucky
      (C3; 08, 20), S. dublin (D1; 01, 9, 12) and S. anatum (E1; 03, 10) using the
      Westphal method. Fifteen cows were found to be seronegative for all 5 of these
      serogroup antigens. Each cow was then vaccinated 3 times at 2-week intervals with
      a killed Salmonella bacterin. The 15 different serotypes used for vaccination
      were chosen to represent a wide array of Salmonella serogroups with a wide array
      of somatic "O" antigens expressed, including somatic antigens 1, 2, 3, 4, 6, 7,
      8, 9, 10, 11, 12, 13, 14, 18, 19, 20, 22, 23, 25, and 27. With each antigen
      tested, the highest ELISA titers were seen with sera from cattle vaccinated with
      homologous O antigens, indicating that reactions were highly O antigen-specific.
      Some cross reactions between subgroups sharing one O factor antigen were found;
      these titers were lower than those found with homologous serogroups sharing 2 or
      more antigens. Only serum from the cow vaccinated from S. anatum (group E;
      antigens 03, 10) cross-reacted at a low titer with group C1 (O somatic antigens
      6, 7) and D1 (O somatic antigens 1, 9, 12) plate antigens, with which no somatic
      antigens were shared. We conclude from these results that Salmonella serology
      using LPS antigens is highly O antigen-specific and predictable.

PMID- 8580170
TI  - Evaluation of a commercial enzyme-linked immunosorbent assay for the diagnosis of
      paratuberculosis in dairy cattle.
AB  - The performance of a commercially available ELISA for detection of antibodies to
      Mycobacterium paratuberculosis was evaluated using sera from 1,146 cows. Samples
      were from uninfected cattle, infected subclinical cattle shedding low numbers of
      organism in feces, subclinical heavy shedders, clinical cases, and randomly
      selected cattle in a slaughterhouse survey for paratuberculosis. The overall
      sensitivity of the test, using the manufacturer's recommended cutoff was 45% +/-
      4.8%, and the specificity was 99% +/- 0.9%. The ELISA result was significantly
      correlated with the number of colonies of M. paratuberculosis detected by fecal
      culturing. The sensitivity of the test was highest for clinical cases of
      paratuberculosis (87% +/- 8.4%), and lowest for subclinical, light-shedding
      cattle (15% +/- 6.6%). Changing the cutoff point did not improve performance of
      the test. Evaluating ELISA results with a kinetic-based method reduced plate-to
      plate variation in results but did not improve performance of the test based on
      receiver-operating characteristic curve analysis.

PMID- 8580171
TI  - Comparison of diagnostic tests for bacterial kidney disease in juvenile steelhead
      trout (Oncorhynchus mykiss).
AB  - In order to accurately diagnose bacterial kidney disease caused by Renibacterium
      salmoninarum in steelhead trout, kidney tissue from experimentally infected fish
      was evaluated using a commercially available enzyme-linked immunosorbent assay
      (ELISA) test kit, fluorescent antibody (FA) testing, bacteriologic culture, and
      histopathology. Seventy-five steelhead trout were randomly assigned to 1 of 4
      groups and intraperitoneally inoculated with 0.15 ml saline (n = 20), 1 x 10(10)
      organisms/ml (n = 18), 1 x 10(8) organisms/ml (n = 18), or 1 x 10(6) organisms/ml
      (n = 19) of R. salmoninarum. ELISA, FA and bacteriologic culture were positive
      for R. salmoninarum from the kidney tissue of the 2 groups infected with the
      highest doses. Although the ELISA and FA tests were accurate when compared to the
      bacteriologic culture from the 2 groups infected with higher doses of the
      organism, they were less sensitive at the lowest level of inoculum.
      Histopathology was not specific for this disease; however, all infected fish had
      a marked proliferative histiocytic interstitial nephritis, characterized by
      marked expansion of the renal hematopoietic tissue by histiocytes without tissue
      necrosis. Other microscopic findings included splenitis and myositis (at the
      injection site) of some fish.

PMID- 8580172
TI  - Examination of gills from salmonids with bacterial gill disease using monoclonal
      antibody probes for Flavobacterium branchiophilum and Cytophaga columnaris.
AB  - Bacterial diseases of the gills of commercially reared salmonids in freshwater
      are common problems. They accounted for 18% of all diagnostic submissions to the
      Atlantic Veterinary College from commercial fish hatcheries. Definitive diagnosis
      is difficult because of the growth characteristics of the putative bacteria in
      culture. Research into the pathogenesis of these diseases has also been similarly
      limited. Monoclonal antibodies (MAbs) were developed to 2 globally significant
      gill bacterial pathogens, Flavobacterium branchiophilum, the causative agent of
      bacterial gill disease, and Cytophaga columnaris, the causative agent of
      columnaris disease of salmonids. These MAbs were then used as the basis for an
      indirect fluorescent antibody test to assess archived cases of gill disease in
      our study region. Of the cases tentatively diagnosed based on histopathology as
      bacterial gill disease, 76.2% tested positively with the MAbs to F.
      branchiophilum. Also present within 18.7% of these cases were bacteria which
      reacted positively to the MAbs for C. columnaris. We conclude that the MAbs
      produced are valuable diagnostic and research probes for common bacterial disease
      of the gills of salmon and trout in Atlantic Canada. This study also adds further
      proof that F. branchiophilum acting alone can be sufficient cause for bacterial
      gill disease.

PMID- 8580173
TI  - Evaluation of a commercial automated system and software for the identification
      of veterinary bacterial isolates.
AB  - A commercial gram-negative bacterial autoidentification plate was originally
      developed using bacterial isolates of human origin. Three veterinary diagnostic
      laboratories conducted a 2-phase trial to enhance the database for veterinary
      use. The first phase consisted of testing the plate with 447 bacterial isolates
      of veterinary origin and incorporating that data into the existing database.
      Emphasis was placed on the Actinobacillus, Bordetella, Pasteurella and
      Enterobacteriaceae groups, since the Pseudomonas taxon was quite complete. The
      second phase of the trial consisted of evaluating the enhanced database using 270
      clinical veterinary isolates normally encountered in veterinary laboratories. For
      the Actinobacillus, Bordetella, Pasteurella and Enterobacteriaceae groups, 72% of
      the bacterial isolates were identified correctly to genus and 85% to species
      after 18 hours incubation. All identifications in phase 1 and phase 2 were
      confirmed using conventional methods.

PMID- 8580174
TI  - Role of sodium azide in reducing nonspecific color development in enzyme
      immunoassays.
AB  - Improved enzyme immunoassay (EIA) procedures achieved by incorporating sodium
      azide during predilution of serum samples in a solid-phase EIA for the detection
      of anti-Toxoplasma antibody in swine using a peroxidase conjugate and in all
      washes of a bovine brucellosis rapid card test EIA using alkaline phosphatase
      conjugate are reported. Without this modification, substantial background
      interference was encountered that showed direct correlation with the degree of
      hemolysis of the serum samples. Anti-Toxoplasma gondii antibody-negative samples,
      separated by subjective groupings based on degree of hemolysis, into "clear",
      "slight", and "gross/total" samples, had a mean +/- standard deviation of 0.150
      +/- 0.072, 0.187 +/- 0.105, and 0.232 +/- 0.108, respectively. The incorporation
      of sodium azide during the initial step of serum dilution dramatically eliminated
      the background, giving a mean +/- standard deviation of 0.079 +/- 0.029, 0.076 +/
      0.022, and 0.081 +/- 0.029, respectively. The level of endogenous peroxidase
      activity, a possible factor for this nonspecific interference, was considerably
      elevated in some of the swine sera. The clear, slight, and gross/total categories
      had relative levels of 1%, 2%, and 51% peroxidase activity compared to the
      conjugate peroxidase activity of 100%. Whereas sodium azide could be used only in
      sample predilution in the swine toxoplasmosis peroxidase-conjugate test, in the
      bovine brucellosis alkaline phosphatase-conjugate card test it could be used in
      all wash cycles. Many brucellosis card test results were visually uninterpretable
      because of significant background color when the manufacturer's wash reagent was
      used. The substitution of a wash reagent containing sodium azide eliminated
      background color, giving a visually unambiguous test.

PMID- 8580175
TI  - Comparison of two commercially available single radial immunodiffusion kits for
      quantitation of llama immunoglobulin G.
AB  - Immunoglobin G (IgG) quantitation was performed by a commercially available
      single radial immunodiffusion kit on 528 plasma samples obtained from llamas.
      Fifty samples encompassing the range of values obtained were selected for further
      evaluation. The IgG concentration of these samples was measured by a second
      commercially available single radial immunodiffusion kit and a sodium sulfite
      precipitation kit. gamma-Globulins also were measured. IgG values predicted by
      the single radial immunodiffusion kits were not in agreement. Failure to
      appreciate this lack of agreement could result in misinterpretation of a llama's
      IgG level derived from one kit when clinical guidelines established using the
      other kit are followed.

PMID- 8580176
TI  - Serohematologic alterations in broiler chicks on feed amended with Fusarium
      proliferatum culture material on fumonisin B1 and moniliformin.
AB  - Two hundred twenty-eight male broiler chicks (Columbia x New Hampshire) were
      given feed amended with autoclaved culture material of Fusarium proliferatum
      containing fumonisin B1 (FB1) at 61, 193, and 546 ppm, fumonisin B2 (FB2) at 14,
      38, and 98 ppm, and moniliformin at 66, 193, and 367 ppm in 3 separate feeding
      trials (amounts of toxin in each trial, respectively). Birds were started on
      amended rations at days 1, 7, and 21 and continuing for 14 days. Of serum
      chemistry parameters, only glucose was significantly decreased. Significant
      increases were noted in serum cholesterol, sodium, alkaline phosphatase,
      aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and
      gamma-glutamyl transferase. Of the hematologic parameters, significant decreases
      were noted in red blood cell counts, hemoglobin, packed cell volume, and white
      blood cell counts. Immunologic changes included impaired anti-Newcastle disease
      antibody hemagglutination inhibition titers associated with relative decreases in
      total serum globulins and increases in albumin/globulin ratios. The changes were
      noted in all treatment groups when compared to controls.

PMID- 8580177
TI  - Comparison of four methods for forage nitrate analysis.
AB  - Twenty forage samples were collected and selected for variation in nitrate
      content. Each forage samples was analyzed 4 times by 4 different methods:
      diphenylamine spot plate, spectrophotometric, nitrate-selective electrode, and
      high-performance liquid chromatographic. Five feed extracts were spiked with 2
      different amounts of nitrate and analyzed by each method. The spectrophotometric
      and nitrate-selective electrode had similar percent recoveries, which were close
      to 100%. The nitrate-selective electrode method had the least variation of the 4
      methods. The diphenylamine spot plate method had the poorest average recovery,
      greatest variation, and was the least accurate. The average coefficients of
      variation for all samples within a method were 15%, 12%, 6.4%, and 16 for the
      diphenylamine spot plate, spectrophotometric, nitrate-selective electrode, and
      high-performance liquid chromatographic methods, respectively. The variation in
      the nitrate-selective electrode method was lower (P < 0.05) than the other
      methods. The results from this study suggest that the nitrate-selective electrode
      method is more accurate and precise than the other methods of analysis tested.

PMID- 8580178
TI  - Lead poisoning and toxicokinetics in a heifer and fetus treated with CaNa2 EDTA
      and thiamine.
AB  - Lead (Pb) poisoning of a pregnant heifer was diagnosed based upon clinical signs
      (head pressing, blindness, muscle twitching) and a blood lead concentration of
      1.73 ppm. Blood and urinary Pb half-lives with CaNa2 EDTA/thiamine therapy were
      determined to be 2.08 and 1.38 days, respectively. Many cations (Ca, Fe, Zn, Na,
      Cu), including Pb, were excreted at higher concentrations in urine during
      therapy. Blood (0.425 ppm) and liver (4.85 ppm) Pb concentrations in the fetus
      were 71.7% and 84.3% of the same tissue Pb concentrations of the dam, indicating
      a significant transfer of Pb in utero. Severe polioencephalomalacia was described
      in the adult, and hepatic lysosomes with metallic electron densities were present
      in the fetus.

PMID- 8580179
TI  - Plaque variations in clinical isolates of bovine coronavirus.

PMID- 8580180
TI  - Comparison of immunogold silver staining (IGSS) with two immunoperoxidase
      staining systems for the detection of porcine reproductive and respiratory
      syndrome virus (PRRSV) antigens in formalin-fixed tissues.

PMID- 8580181
TI  - Evaluation of an indirect fluorescent IgM antibody test for the detection of pigs
      with recent infection of porcine reproductive and respiratory syndrome virus.

PMID- 8580182
TI  - Detection of serotype G6 rotavirus in bovine field samples using a nonradioactive
      PCR-derived cDNA probe.

PMID- 8580183
TI  - Papillomavirus infection in raccoons (Procyon lotor).

PMID- 8580184
TI  - Gross and histologic lesions of adenovirus group I in guinea fowl.

PMID- 8580185
TI  - Osteopetrosis, anemia, thrombocytopenia, and marrow necrosis in beef calves
      naturally infected with bovine virus diarrhea virus.

PMID- 8580186
TI  - Comparison of three commercial radial immunodiffusion kits for the measurement of
      canine serum immunoglobulins.

PMID- 8580187
TI  - Abortion in a mare associated with Corynebacterium pseudotuberculosis infection.

PMID- 8580188
TI  - Subcutaneous mycetoma-like granuloma in a horse caused by Aspergillus versicolor.

PMID- 8580189
TI  - Pulmonary histoplasmosis in a llama.

PMID- 8580190
TI  - Recognition of leukochimerism during genotyping for bovine leukocyte adhesion
      deficiency (BLAD) by polymerase-chain-reaction-amplified DNA extracted from
      blood.

PMID- 8580191
TI  - Ovarian remnant syndrome in dogs and cats: 46 cases (1988-1992).

PMID- 8580192
TI  - Cholangioma in a goat.

PMID- 8580194
TI  - Equine colonic lipomatosis.

PMID- 8580193
TI  - Intestinal fibrosis and vascular remodeling in ten horses and two ponies.

PMID- 8580195
TI  - Lead concentrations in frozen and formalin-fixed tissues from raccoons (Procyon
      lotor) administered oral lead acetate.

PMID- 8580196
TI  - Water deprivation--sodium ion toxicosis in cattle.

PMID- 8580197
TI  - A hypochlorite-fast metachromatic quick stain for human megakaryocytes.
AB  - Megakaryocytes in aspirates of normal and abnormal human bone marrow displayed
      rose-pink metachromasia when stained with a violet polymethine dye. The color of
      the megakaryocytes persisted when the stained sample was exposed to a dilute
      solution of sodium hypochlorite. Under the same conditions, other hematopoietic
      cells became colorless. This stain may be useful for demonstrating megakaryocyte
      from both healthy and diseased bone marrow specimens.

PMID- 8580199
TI  - A color image analysis method for assessment of germination based on differential
      fluorescence staining of bacterial spores and vegetative cells using acridine
      orange.
AB  - Color fluorescence image analysis of acridine orange (AO) stained germinating
      Bacillus subtilis var. niger bacteria revealed a cell population initially
      dominated by small green spores followed by the emergence of at least three
      additional discernible subpopulations in response to stimulation with D-glucose.
      These subpopulations were small, round or oblong red cells; intermediate to large
      metachromatic cells; and large red rods. Large green rods were rarely observed.
      An increase in red emissions (i.e., putative RNA synthesis) was sometimes seen as
      early as 90 min after exposure to D-glucose and uptake of AO at room temperature.
      This may represent either metabolic recovery from quiescence or RNA synthesis
      associated with germination. In the absence of D-glucose, or using autoclaved
      bacteria in the presence of glucose, no relative increase in the red signal was
      observed despite hours of observation. Digital image analysis was used for
      relative measurement of red, green and blue signals and to correlate the size of
      various subpopulations with their fluorescence color emissions over time. Image
      analysis demonstrated a trend toward increasing size and red emission in the
      presence of glucose. The average red emission was found to be a good
      discriminator of the various subpopulations, while the average green emission was
      approximately equal among the subpopulations making it a poor discriminator.
      These data suggest that AO staining might be used for rapid computer-assisted
      discrimination of spores vs. vegetative cells.

PMID- 8580198
TI  - Bromodeoxyuridine and iododeoxyuridine double immunostaining for epoxy resin
      sections.
AB  - To establish bromodeoxyuridine (BrdUrd)/iododeoxyuridine (IdUrd) double
      immunostaining for thick sections of epoxy resin-embedded tissues, young hamsters
      received intra-peritoneal injections of IdUrd and BrdUrd 3 hr and 1 hr before
      sacrifice, respectively. The intestines were fixed with phosphate-buffered 4%
      paraformaldehyde and embedded in an Epon-Araldite mixture. The epoxy resin was
      removed completely by a sodium methoxide/benzene/methanol solution. This epoxy
      resin removal method was effective for BrdUrd/IdUrd immunostaining using a mono
      specific antibody for BrdUrd (Br-3) and a bi-specific antibody for BrdUrd (Br-3)
      and a bi-specific antibody for BrdUrd and IdUrd (IU-4), followed by the ABC
      complex method. Epoxy sections stained with these antibodies showed clear
      localization of nuclei incorporating the two thymidine analogues with precise
      morphology of labeled cells. Furthermore, ultrastructural observation of thin
      sections adjacent to thick sections immunostained for BrdUrd/IdUrd confirmed the
      cell type and ultrastructural features of cells labeled with these thymidine
      analogues.

PMID- 8580200
TI  - Fluoresein diacetate uptake to determine the viability of human fetal cerebral
      cortical cells.
AB  - We investigated the accuracy of fluorescein diacetate uptake as an indicator of
      the viability of human fetal cerebral cortical cells. Cortical cells from 16-26
      week-old normal fetuses were studied. The cortices were dissociated mechanically
      with normal saline to make a suspension. Fluorescein diacetate uptake and trypan
      blue exclusion were compared as methods for examining cell viability. Our results
      show that fluorescein diacetate uptake is a simple and sensitive method for
      examining human fetal cortical cell viability.

PMID- 8580201
TI  - Glycol methacrylate embedding of alginate-polylysine microencapsulated pancreatic
      islets.
AB  - A method for processing and embedding alginate-polylysine microencapsulated
      pancreatic tissue in glycol methacrylate resin (GMA) is described. Fixation in 4%
      phosphate buffered formaldehyde, processing in ascending concentrations of glycol
      methacrylate monomer and embedding in Technovit 7100 results in well preserved
      morphological details of hydrogels, hydrogel-cell interfaces, and encapsulated
      pancreatic tissue. Routine staining with Loeffler's methylene blue, hematoxylin
      and eosin, and Romanovsky-Giemsa gave excellent images of the GMA embedded
      alginate polylysine membrane and tissues allowing cells on the outside of the
      capsule to be analyzed effectively as part of the foreign body reaction against
      the capsule membrane.

PMID- 8580202
TI  - Osmium tetroxide-potassium ferrocyanide intensification of a diaminobenzidine
      product obtained by photoconversion of a fluorescent label: a study of human
      neutrophil granules.
AB  - A diaminobenzidine posttreatment employing osmium tetroxide and potassium
      ferrocyanide was successfully used to intensify the diaminobenzidine stain formed
      by photoconversion of immunofluorescent labelling. Lactoferrin labelled granules
      became visible following the photoconversion process. Adequate diaminobenzidine
      staining was obtained after irradiating the cytospin preparations with
      ultraviolet light for 30-40 min. The diaminobenzidine stain had advantages over
      the fluorescent stain owing to its greater stability, greater density, and
      ability to be intensified. The enhancement procedure intensified both the color
      and density of the diaminobenzidine product. Consequently, shorter irradiation
      times could be used. Osmium tetroxide solutions of 3-4% increased the intensity
      with minimal background staining. Ultrastructural immunogold cytochemistry on
      ultrathin sections confirmed the existence of the lactoferrin labelled structures
      observed by light microscopy of cytospin preparations indicating that these were
      secondary granules. The photomicroscopy procedures used in this study were simple
      to perform and could be applied to studies of other cellular antigens prior to
      using immunoultramicroscopy.

PMID- 8580203
TI  - Immunohistochemical detection of epidermal growth factor in glycol methacrylate
      embedded tissue.
AB  - This study addresses a variety of immunohistochemical conditions for detecting
      EGF in 3.5% paraformaldehyde fixed, glycol methacrylate embedded tissue including
      antigen unmasking with trypsin, dilution of primary antibody, and incubation time
      with primary antibody. Color development was achieved with a biotinylated
      secondary antibody linked to an avidin biotinylated peroxidase complex.
      Trypsinization and a 12 hr incubation with the primary antibody was essential to
      detect EGF in this system. Adequate staining could be achieved with a 1:100
      dilution of the primary antibody.

PMID- 8580204
TI  - Improvements for observing Anthurium (Araceae) floral structures by light
      microscopy.
AB  - Three major obstacles must be overcome in the anatomical study of Anthurium
      floral structure and embryo development including presence of mucilage, hardened
      carpel walls, and hardened seed coat in the developing fruit and seed. Fixation
      in 6% glutaraldehyde and 1% cetylpyridinium chloride in 0.05 M sodium cacodylate,
      pH 6.8, effectively fixed or removed mucilage from the locules of Anthurium
      andraeanum Hort. in spadices. This treatment enhanced infiltration of the
      embedding medium through the hardened carpel wall into the locule space and
      decreased the quantity and size of holes in the embedding block during
      sectioning. Specimens 16 weeks after pollination could be fixed, infiltrated, and
      observed without physical removal of the seed coat. Embryos may be excised from
      the seed at later stages without compromising embryo structure.

PMID- 8580205
TI  - Epipolarization microscopic immunogold assay: a combination of immunogold silver
      staining, enzyme-linked-immunosorbent assay and epipolarization microscopy.
AB  - We describe a new immunoassay which combines an immunosorbent assay, immunogold
      silver staining and epipolarization microscopy. Our new assay procedure features
      multiple samples on a single microscope slide, and high sensitivity of
      epipolarization microscope for detection of silver-enhanced colloidal gold as a
      final immunoassay product. We call the new immunoassay "on slide immunogold
      assay" (OSIGA). This new method uses biotinylated antibody and streptavidin-gold
      reaction with silver enhancement technique. With OSIGA it is possible to
      investigate 30 samples on a single microscopic slide. Our preliminary studies
      used 10-20 microliter samples and detected nanogram quantities of a standardized
      protein solution. Unlike enzyme linked immunosorbent assay (ELISA), which has a
      limited time for reading the final color products, the OSIGA specimens can be
      dried or resin mounted for longer storage and future reference.

PMID- 8580206
TI  - DAPI: a DNA-specific fluorescent probe.
AB  - DAPI (4',6-diamidino-2-phenylindole) is a DNA-specific probe which forms a
      fluorescent complex by attaching in the minor grove of A-T rich sequences of DNA.
      It also forms nonfluorescent intercalative complexes with double-stranded nucleic
      acids. The physicochemical properties of the dye and its complexes with nucleic
      acids and history of the development of this dye as a biological stain are
      described. The application of DAPI as a DNA-specific probe for flow cytometry,
      chromosome staining, DNA visualization and quantitation in histochemistry and
      biochemistry is reviewed. The mechanisms of DAPI-nucleic acid complex formation
      including minor groove binding, intercalation and condensation are discussed.

PMID- 8580208
TI  - Detecting enzymatic activity in cells using fluorogenic substrates.
AB  - Fluorogenic substrates can detect enzymatic activity associated with cells. It is
      difficult, however, to detect activity within a single cell or in an organelle
      since hydrolytic substrates yield products that rapidly leak from the cell.
      Several new solutions are presented including trapping the fluorescent product in
      membranes, in cell organelles, or as a glutathione conjugate. Novel substrates
      also are described that directly yield highly fluorescent precipitates at the
      site of enzymatic activity. These can be used for detecting endogenous activity
      in cells or for enzyme-amplified histochemical detection. Some of these
      substrates can be used in live cells.

PMID- 8580207
TI  - Application of biotin, digoxigenin or fluorescein conjugated deoxynucleotides to
      label DNA strand breaks for analysis of cell proliferation and apoptosis using
      flow cytometry.
AB  - A flow cytometric method has recently been developed using biotinylated dUTP (b
      dUTP) in a reaction catalyzed by terminal deoxynucleotidyl transferase (TdT) to
      identify the endonuclease-induced DNA strand breaks occurring during apoptosis.
      Counterstaining of DNA makes it possible to relate apoptosis to cell cycle
      position or DNA index. In the present study, we compared this method with one
      using digoxigenin-conjugated dUTP (d-dUTP) to label apoptotic cells. The
      discrimination of apoptotic from nonapoptotic cells was similar when
      incorporation of d-dUTP was compared with b-dUTP. Both techniques resulted in a
      20-30 fold increase in staining of apoptotic over nonapoptotic cells although
      somewhat less background fluorescence was observed with the d-dUTP. Direct
      labeling with fluoresceinated dUTP (f-dUTP) was less sensitive in detecting DNA
      strand breaks, but had the advantage of simplicity. The principle of labeling DNA
      strand breaks using TdT was also employed to identify DNA replicating cells. To
      this end, the cells were incubated in the presence of BrdUrd, then exposed to UV
      light to selectively photolyse DNA containing the incorporated BrdUrd. DNA strand
      breaks resulting from the photolysis were then labeled with b-dUTP or d-dUTP.
      This approach is an alternative to immunocytochemical detection of BrdUrd
      incorporation, but unlike the latter does not require prior DNA denaturation,
      thus can be applied when the denaturation step must be avoided. The method was
      sensitive enough to recognize DNA synthesizing cells that were incubated with
      BrdUrd for only 5 min, the equivalent of replication of less than 1% of the
      cell's genome. The discrimination between apoptotic vs. BrdUrd incorporating
      cells is based on different extractability of DNA following cell fixation. This
      method can be applied to analyze both cell proliferation (DNA replication) and
      death (by apoptosis) in a single measurement.

PMID- 8580209
TI  - An improved immunolabeling method for microtubular cytoskeleton in poplar
      (Populus nigra L.) free nuclear endosperm.
AB  - We investigated immunocytochemical staining of microtubular cytoskeleton of free
      nuclear endosperm, a tissue which is particularly difficult to fix. This tissue
      requires fixation for 45 hr to preserve the integrity of the microtubular network
      after paraformaldehyde based fixation. Low glutaraldehyde concentration in the
      fixative and the ethanol dehydration retains beta-tubulin antigenicity and the
      former improves preservation of tissue structure. An ethanol-free embedding
      method is recommended for immunocytochemical studies of ethanol sensitive target
      proteins.

PMID- 8580210
TI  - A vanadate hematoxylin stain for basic proteins.
AB  - Ammonium vanadate can act as both an oxidant and a mordant for hematoxylin.
      Lithium carbonate can remove vanadate hematoxylin from other structures so that
      only the most basic proteins are stained. Brief diazotization of the tissue
      sections restricts staining to the histone proteins of the nucleus.

PMID- 8580211
TI  - Novel fixation of plant tissue, staining through paraffin with alcian blue and
      hematoxylin, and improved slide preparation.
AB  - Onion (Allium cepa) root tips were fixed in a proprietary solution without
      aldehyde, toxic metals or acetic acid. Fixed specimens were embedded in paraffin,
      sectioned on a rotary microtome and mounted on detergent-washed slides without
      adhesive. Slides with ribbon segments affixed were immersed in 0.2% aqueous
      alcian blue 8GX in screw-capped Coplin jars in a water bath at 50 C for 1 hr.
      Excess alcian blue was rinsed off under cold running tap water and the slides
      were immersed in quick-mixed hematoxylin at room temperature for 15 min. Stained
      slides were deparaffinized, rinsed with isopropanol, air dried, and coverslips
      were affixed with resin. Thus, the traditional paraffin microtechnique has been
      modified at all steps from fixation to finishing slides with coverslips.

PMID- 8580212
TI  - Azure B-eosin APAAP staining: a method for simultaneous hematological and
      immunological cell analysis.
AB  - Azure B-eosin APAAP staining allows simultaneous analysis of peripheral blood and
      bone marrow cells for hematological characteristics and immunological cell marker
      profiles. A defined sequence of staining procedures maintains characteristic
      components of the Romanowsky-Giemsa stain whereas cell antigens can be detected
      immunologically using the alkaline phosphatase-anti-alkaline phosphatase (APAAP)
      detection system. Antigens are visualized by the staining product of the
      substrate-naphthol AS GR phosphate and variamine blue salt. The usefulness of the
      azure B-eosin APAAP method was demonstrated on blood and bone marrow smears of
      patients with various hematological disorders.

PMID- 8580213
TI  - Identification of normal and abnormal human megakaryocytes based on acid fast
      metachromasia after staining with basic black MSP.
AB  - Megakaryocytes from normal persons and from patients with immune thrombocytopenic
      purpura, myelodysplastic disorders, hypersplenism, and essential thrombocythemia
      displayed vivid magenta metachromatic staining of the cytoplasm when stained with
      basic black MSP followed by brief exposure to dilute hydrochloric acid. Under the
      same conditions, other hematopoietic cells were completely decolorized. Acid fast
      metachromasia of megakaryocytes facilitates their identification, particularly in
      cases of small and atypical megakaryocytes found in disease states.

PMID- 8580214
TI  - Influence of postnatally administered glucocorticoids on rat lung growth.
AB  - Postnatal formation of alveoli can be largely prevented by glucocorticoid
      treatment, which accelerates alveolar wall thinning and inhibits outgrowth of new
      interalveolar septa. Since a double capillary network is a prerequisite for
      interalveolar wall formation, we hypothesized that glucocorticoid treatment
      inhibited alveolar formation, indirectly, by inducing precocious microvascular
      maturation. Between 4 and 60 days we followed up qualitatively and quantitatively
      the effects of 2 weeks (days 2-15) of daily Decadron (Dexamethasone phosphate)
      injections on the lung structure. Glucocorticoid induced only small changes in
      body weight or lung volume. However, during the first 2 weeks, it accelerated
      alveolar wall thinning and microvascular maturation and partly suppressed the
      outgrowth of new interalveolar septa. In Decadron-treated rats, the interstitial
      tissue mass was significantly reduced during the first 2 weeks, and a larger
      alveolar surface area was endowed with a capillary monolayer on days 10 and 13.
      One week after drug withdrawal, the trend towards precocious maturation of the
      lung was reversed. Lipofibroblasts reappeared, and inter-airspace septa regressed
      towards a more immature state. We found indications of a second burst of
      alveolization by resumption of secondary septa formation. The late sequelae of
      Decadron treatment (day 60) were manifested as an 'emphysematous' condition of
      the lungs, with larger and fewer airspaces, the delayed alveolization being
      insufficient to compensate for the initial deficit.

PMID- 8580215
TI  - Pulmonary effects after surfactant treatment in premature infants with severe
      respiratory distress syndrome.
AB  - To understand the mechanisms behind the improved oxygenation after intratracheal
      surfactant instillation, the immediate effects of lung volume and pulmonary
      mechanics were analyzed. All infants studied were enrolled in multicenter trials
      in which surfactant therapy was instituted according to a rescue protocol.
      Infants received either synthetic surfactant (Exosurf) or modified porcine
      surfactant (Curosurf). Measurements of lung volume and pulmonary mechanics were
      successfully performed in 12 patients with a birth weight of 1.3 +/- (SD) 1.4
      weeks. Functional residual capacity (FRC) and pulmonary mechanics were measured
      during mechanical ventilation. The FRC increased significantly by 70% (median),
      from 7.10 +/- (SD) 2.8 ml/kg to 11.5 +/- 3.3 ml/kg after surfactant instillation.
      However, a concomitant decrease in specific compliance was also seen. These
      findings could suggest that this immediate increase in FRC is initially
      nonuniform. However, since no significant correlation between changes in FRC and
      improvement in arterial-to-alveolar oxygen tension ratio is seen, other effects
      of surfactant must also be considered. These could include local and/or systemic
      changes in hemodynamics, such as decreased shunting as well as various effects on
      gas diffusion.

PMID- 8580216
TI  - Bone mineral status in preterm-born children: assessment by dual-energy X-ray
      absorptiometry.
AB  - To elucidate the long-term consequences of osteopenia of prematurity, lumbar
      spinal bone mass was measured in 21 preterm-born children aged 3-4 years by dual
      energy X-ray absorptiometry. Their mineral intake remained low during early life,
      and all 11 infants previously studied were osteopenic at term postconception. At
      the age of 3-4 years, however, all 21 children were found to have normal bone
      mineral content and density with slightly elevated serum osteocalcin levels. Our
      results show that in preterm-born children spontaneous resolution of lumbar
      spinal osteopenia occurs during early childhood.

PMID- 8580217
TI  - CD26 and CD31 surface antigen expression on human colostral T cells.
AB  - The expression levels of CD26 and CD31 surface antigens, two adhesion/activation
      molecules with helper and suppressor activities, respectively, were found to be
      significantly higher on human colostral T cells (CD3+) than in autologous
      peripheral blood samples. These findings provide further phenotypical evidence
      that immune system T lymphocytes are compartmentalized in the mammary gland late
      in pregnancy and during lactation. The question of whether these overexpanded T
      lymphocyte populations in breast milk modulate in situ, either by enhancing or
      suppressing, the cellular and/or humoral immune response of the suckling infant
      remains to be answered. Additional studies are, therefore, needed to explore this
      intriguing field concerning the immunology of the colostrum.

PMID- 8580218
TI  - Impaired neutrophil phagocytosis in preterm neonates: lack of correlation with
      expression of immunoglobulin or complement receptors.
AB  - Preterm neonates are vulnerable to infection as a result of a compromised immune
      system. The function of neutrophils from 'well', 'stressed', and 'maturing'
      preterm neonates was compared with term neonate and adult neutrophils using a
      whole-blood phagocytosis assay. Cell surface expression of complement receptors
      and immunoglobulin G receptors was measured on neutrophils in whole blood from
      the same samples. Fewer actively phagocytosing neutrophils were found in all
      preterm neonate samples, especially in maturing neonates. Phagocytic rates were
      slower, and the number of Escherichia coli ingested was smaller in preterm
      neonate than in term neonate neutrophils. Expression of immunoglobulin G
      receptors and complement receptor 3 on neutrophils was not directly related to
      phagocytic activity.

PMID- 8580219
TI  - Effect of state of alertness on the heart rate response to ocular compression in
      human infants.
AB  - Because the state of alertness exerts a profound influence on autonomic cardiac
      control, we hypothesized, that the heart rate response to a vagal stimulus, i.e.,
      ocular compression, may differ during different states of alertness. We studied 8
      healthy infants with a postconceptional age of 35-41 weeks (mean +/- SD 37.9 +/-
      2.1 weeks). They underwent a standardized ocular compression test during
      polygraphically controlled wakefulness, rapid eye movement (REM) sleep, and non
      REM (NREM) sleep. The R-R intervals were measured (1) during the 60 s preceding
      the ocular compression test, to determine the mean control R-R interval, and (2)
      during compression. Percent R-R interval was defined as the longest R-R interval
      in milliseconds during the test divided by the mean control R-R interval and
      multiplied by 100. The longest R-R interval during the test was significantly
      greater in REM sleep than in wakefulness (p < 0.05) and in NREM sleep (p <
      0.01):939 +/- 360, 623 +/- 355, and 538 +/- 60 ms, respectively. The percent R-R
      interval was significantly greater in REM sleep than in NREM sleep (p < 0.01):236
      +/- 91 and 129 +/- 16, respectively. The time from the longest R-R interval to
      return to mean control R-R interval, i.e., vagal escape, was significantly
      shorter in REM sleep than in NREM sleep and in wakefulness (p < 0.01): 843 +/-
      168, 2,131 +/- 712, and 2,078 +/- 913 ms, respectively. This study indicates that
      the state of alertness should be defined when performing tests on autonomic
      reflexes in infants.

PMID- 8580220
TI  - Paediatric clinical pharmacology in the former Soviet Union: Ukraine.
AB  - Among the many challenges facing the newly created states formed in Eastern
      Europe and Central Asia after the collapse of the Soviet Union is the development
      of medical education and health care independent of many of their former ties to
      Moscow, Ukraine, the largest of these states following the Russian Republic, is
      facing many of these challenges. Paediatric clinical pharmacology is markedly
      underdeveloped in the Ukraine. There is little clinical pharmacology content in
      undergraduate medical education and essentially none in postgraduate training.
      Underdevelopment of paediatric clinical pharmacology also increases difficulties
      faced because of lack of a domestic pharmaceutical industry. This situation
      compounds the difficulty of how physicians in Ukraine can best learn to choose
      and apply rational individualized therapy.

PMID- 8580221
TI  - Glucose and insulin tolerance tests in the rat on different days of gestation.
AB  - To study insulin/glucose relationship during gestation, rats were studied on days
      6, 12, 15, 18, 20 or 21 of pregnancy and the results were compared to values in
      sex-matched virgin control rats. Blood glucose levels were decreased on days 20
      and 21 of gestation whereas plasma insulin levels appeared decreased on days 6
      and 12, unchanged on day 15 and enhanced on days 18, 20 and 21 of gestation.
      Total pancreas insulin content was already augmented on day 6 of gestation and
      continued to increase with gestational time. With the exception of an increase in
      the 6-day-pregnant rats 22.5 min after an oral glucose load, blood glucose levels
      did not differ between 6- or 12-day-pregnant rats and virgin controls although
      plasma insulin levels reached higher values on these days. However, in the 15-day
      pregnant rats, glucose tolerance after the glucose load was enhanced while plasma
      insulin levels did not differ from those in virgin rats during the first 30 min.
      In the 18-day-pregnant rat blood glucose was more increased but plasma insulin
      did not differ after the glucose load when compared to virgin rats, whereas 20-
      or 21-day-pregnant rats showed a glucose tolerance similar to that of virgin rats
      but their insulin levels shortly after the glucose load were higher. The
      hypoglycemic response to a high intravenous dose of insulin was decreased in 12-,
      18-, 20- and 21-day-pregnant rats. Therefore, whereas in both the 6- and 12-day
      pregnant rats there is an enhanced beta-cell response to the glucose
      insulinotropic effect and insulin responsiveness is reduced in 12-day-pregnant
      rats, the 15-day pregnant rat is in a transitory stage where both insulin
      sensitivity and the beta-cell response return to nonpregnant values. However,
      from 18 days of gestation on, there is an intense insulin-resistant condition
      which is only partially compensated by an enormous accumulation of insulin in the
      pancreas followed by a faster and larger insulin release after a glucose load.

PMID- 8580222
TI  - Molecular forms of atrial natriuretic peptide in atria and plasma from fetal and
      adult female rats.
AB  - Molecular forms of atrial natriuretic peptide (ANP) were determined by
      chromatography on Sephadex G50 fine coupled with a radioimmunoassay for rANP(1
      28) in left and right atrial extracts and acidified plasmas from 17-, 19- and 21
      day-old fetuses and adult female rats. Chromatographic analyses revealed two
      immunoreactive peaks of rANP with an apparent molecular weight of about 25 and 12
      kD, respectively, in all atrial extracts from fetal and adult rats. Only one
      immunoreactive peak of rANP with an apparent molecular weight of about 3 kD was
      detected in all fetal plasmas. The 25- and 12-kD ANP molecular forms isolated
      from fetal atrial tissue and incubated with thrombin for 30 min at 37 degrees C
      were converted to ANP material with a molecular weight of about 3 kD. These
      results suggest that the two high molecular weight forms stored in fetal atrial
      tissue should be precursors of circulating rANP molecules, and the rat fetus
      should possess the same posttranslational processing of the precursor molecule as
      the adult rat as early as day 17 of gestation.

PMID- 8580223
TI  - Withdrawal-emergent dyskinesia in patients with schizophrenia during
      antipsychotic discontinuation.
AB  - We examined whether patients exhibiting withdrawal-emergent dyskinesia (WE-D)
      represent a group vulnerable to subsequent development of tardive dyskinesia
      (TD). WE-D was defined as moderate abnormal movements during antipsychotic
      withdrawal in persons without persistent TD. We assessed patients with
      schizophrenia-spectrum illness participating in withdrawal from antipsychotic
      medication. Patients with WE-D were compared to those without dyskinesia and to
      those with persistent TD. Clinical measures included duration of illness and
      antipsychotic exposure, negative symptoms, and neurologic soft signs. We
      hypothesized that WE-D patients would not differ from persistent-TD patients
      across the above variables, but would differ from non-TD patients. Patients
      without TD significantly differed from persistent TD in duration of illness,
      medication exposure and neurologic soft signs. WE-D did not differ from TD across
      these measures. No-TD patients also showed less duration of medication exposure
      and neurologic soft signs than those with WE-D.

PMID- 8580224
TI  - Growth hormone secretion timing in depression: clinical outcome comparisons.
AB  - Growth hormone (GH) secretion in the 100 minutes preceding sleep onset (preSO),
      as well as in the first half of the night (1st HN), was examined for a group of
      13 healthy women and 43 women with recurrent depression who participated in a 3
      year maintenance therapy study. GH studies were obtained at several points during
      treatment and every 3 months during maintenance, during which patients were
      randomly assigned to active drug or drug-free maintenance treatment cells for 3
      years, or until recurrence of depression. Depressed patients were divided into
      subgroups according to their maintenance treatment assignment (active drug or
      drug free) and treatment outcome (completing in remission or having a
      recurrence). Imipramine caused an increase in the GH ratio in all subgroups.
      Protocol completers had a significantly larger imipramine-induced increase in the
      GH ratio than did recurrers. The difference in time of GH secretion relative to
      sleep onset was found to correlate with treatment outcome and was independent of
      medication status during maintenance.

PMID- 8580225
TI  - Tyramine conjugation deficit in migraine, tension-type headache, and depression.
AB  - This study was designed to investigate tyramine sulfate conjugation in patients
      with migraine or tension-type headache, as defined by the newly introduced
      International Headache Society (IHS) criteria and to examine whether this
      relationship is mediated by major depression. A total of 62 subjects completed
      the study: 38 with migraine (22 with aura and 16 without aura), 12 with tension
      type headache, and 12 controls. Patients with migraine had significantly lower
      urinary tyramine sulfate excretion following oral tyramine challenge than normal
      control. Tension-type headache was also associated with low tyramine conjugation,
      but only when comorbid with depression. Although mean tyramine sulfate output was
      lower among subjects with major depression within each of the subtypes of
      headache, no significant main effect emerged for depression or major subtype
      thereof. The lower tyramine sulfate excretion values among patients with both
      migraine and depression compared to those of migraine alone or depression alone
      in our data and those of others suggests that comorbid migraine with depression
      may represent a more severe form of migraine than migraine alone. The findings
      underscore the importance of comorbidity in clinical and epidemiological studies
      of migraine.

PMID- 8580226
TI  - Cerebrospinal fluid gamma-aminobutyric acid in patients with panic disorder.
AB  - Cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) levels were measured in
      11 patients with panic disorder (PD) prior to and following 7 months of treatment
      with alprazolam or imipramine and in six neurological control patients. Although
      a clear treatment response was observed in patients with PD, neither alprazolam
      nor imipramine significantly changed CSF GABA during the treatment period. A
      negative correlation was demonstrated between baseline CSF GABA and posttreatment
      overt psychopathology. Low pretreatment level of CSF GABA correlated
      significantly with poor therapeutic outcome, judged by the amount of anxiety and
      depression as well as by the frequency of panic attacks at the end of follow-up.

PMID- 8580227
TI  - Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in
      healthy volunteers.
AB  - A randomized, placebo-controlled, double-blind, three-way crossover design was
      used to evaluate the effectiveness of single oral 100 mg doses of CI-988, a
      cholecystokinin B (CCKB) antagonist, in attenuating panic symptoms induced by
      intravenous injection of cholecystokinin-tetrapeptide (CCK-4). Thirty healthy men
      received the following treatments on three separate occasions: placebo
      capsules/placebo, placebo capsules/CCK-4, or CI-988 capsules/CCK-4. There was no
      marked difference in the number, time to onset, or duration of panic symptoms
      between CI-988/CCK-4 and placebo/CCK-4. There was, however, a 14% difference in
      sum intensity scores between these treatments that was statistically significant
      (p = 0.039). The symptoms most affected by CI-988 were cold chills/hot flushes,
      chest pain/discomfort, and anxiety/fear/apprehension. Panic attack frequency also
      decreased following CI-988 treatment (8/30 vs. 16/30; p = 0.035). This decrease,
      amid otherwise modest effects, could be explained by a preferential effect of CI
      988 on the subjective experience of anxiety/fear/apprehension. Possible reasons
      for the relatively modest effects of CI-988 on CCK-4-induced panic symptoms are
      discussed.

PMID- 8580228
TI  - Influence of phototherapy treatment duration for seasonal affective disorder:
      outcome at one vs. two weeks.
AB  - Most previous phototherapy research has been conducted on trials of 1 week
      duration. This study compares response to phototherapy at weeks 1 and 2. All
      subjects (n = 26) were between 18 and 65 years and met Diagnostic and Statistical
      Manual of Mental Disorders, 3rd ed, revised, (DSM III-R) criteria for major
      depression, recurrent, seasonal pattern and had a Hamilton Depression Rating
      Scale score (HAM-D) > or = 20. A rater blinded to treatment schedule and study
      hypothesis repeated the HAM-D-31 1 and 2 weeks after baseline to assess treatment
      response to bright light. Response rates at week 1 defined by 50% reduction in
      HAM-D-31 and HAM-D-31 score < 8 were 62% and 27%, respectively. At week 2,
      however, 65% had a 50% reduction in HAM-D-31 and 62% had a HAM-D-31 < score 8
      (chi-square = 6, p = 0.01). Four patients (15%) who were nonresponders at week 1
      responded after 2 weeks. The results show a statistically different outcome after
      2 weeks of treatment and suggest the necessity of longer trials of phototherapy.

PMID- 8580229
TI  - Effects of intravenous cocaine on plasma cortisol and prolactin in human cocaine
      abusers.
AB  - The aim of the present work was to examine the cortisol and prolactin responses
      to acute cocaine administration in human cocaine users. Each subject served as
      his own control during intravenous saline placebo and cocaine (40 mg) infusion
      sessions. Cocaine significantly elevated plasma cortisol but did not affect
      prolactin. The rise in cortisol coincided with an increase in heart rate and
      blood pressure after cocaine. In agreement with studies in animals, our data
      suggest that cocaine activates the hypothalamic-pituitary-adrenal axis in humans.
      However, based on the well-known importance of dopamine as a prolactin-inhibiting
      factor, the failure of cocaine to suppress prolactin in the present study raises
      questions concerning the role of dopamine in the mechanism of acute cocaine
      action in humans.

PMID- 8580230
TI  - Monoamine oxidase A and B activities in heavy smokers.
AB  - There is a strong association between depression and smoking. Because monoamine
      oxidase (MAO) inhibition leads to antidepressant effect and in vitro studies have
      shown that cigarette smoke inhibits MAO activity, it is conceivable that smoking
      may have an antidepressant effect, if smokers have reduced MAO activity.
      Therefore, we assessed platelet MAO-B activity and plasma concentration of
      catecholamine metabolites reflecting MAO-A activity in heavy dependent smokers
      and nonsmokers matched for sociodemographic characteristics. Platelet MAO-B
      activity, plasma 3,4-dihydroxyphenylglycol, plasma 3,4-dihydroxyphenylacetic
      acid, and plasma 3,4-dihydroxyphenylalanine concentrations were significantly
      lower in smokers than in nonsmokers, whereas plasma norepinephrine did not
      differ. Significantly more smokers reported previous history of depression, manic
      episode, panic attack, agoraphobia, and simple phobia. Smokers had higher scores
      (p < 0.001) on the Montgomery-Asberg Depression Rating Scale (MADRS) and the
      Hamilton Anxiety Scales. It is concluded that the activities of both forms of the
      MAO are reduced in heavy dependent smokers.

PMID- 8580231
TI  - Clozapine does not elevate serum prolactin levels in healthy men.

PMID- 8580232
TI  - Yohimbine augmentation of fluvoxamine in refractory depression: a single-blind
      study.

PMID- 8580233
TI  - Depression and heart rate variability.

PMID- 8580234
TI  - Immune differences in children with and without depression.

PMID- 8580235
TI  - Is platelet imipramine binding reduced in depression? A meta-analysis by Ellis
      and Salmond.

PMID- 8580236
TI  - Serum iron in catatonia.

PMID- 8580237
TI  - [Contamination by inhalational anesthetics on the intensive care unit--sequelae
      of an unnecessary sedation regimen?].

PMID- 8580238
TI  - [Percutaneous dilatative tracheotomy--an alternative or improved technique for
      the intensive care patient].

PMID- 8580239
TI  - [Intravenous anesthesia--current aspects].
AB  - Intravenous anaesthesia as a defined technique has become popular in recent
      years, since new developed drugs and more sophisticated application systems were
      introduced into clinical practice. However, only a minority of anaesthesiologists
      really practise this new technique. The scientific basis of continuous
      intravenous anaesthesia has not been spread widely in the anaesthetic community
      yet. The following review therefore focusses on recent findings and developments
      in the field of pharmacology, pharmacokinetics, pharmacodynamics and modern
      application systems of intravenous anaesthetic drugs. The new opioid remifentanil
      is described, new aspects in the interpretation of pharmacokinetic data are
      presented and the concept of context-sensitive halftimes as a parameter to
      estimate the decrease in clinical effect of intravenous anaesthetics is
      introduced. Drug effect in clinical anaesthesia is a result of equilibration of
      the drug with the effect site (Biophase). By means of defining the effect site
      equilibration time (t1/2ke0 and the drugs concentration at which this effect is
      achieved (Cp50) the pharmacodynamic properties of each intravenous anaesthetic
      can be characterised. Computerised pharmacokinetic data can be used to generate
      stable drug concentrations (target plasma concentration) when connected to an
      infusion pump. These target controlled systems are able to reach a predefined
      level rapidly and to maintain it. Thus pharmacodynamic interactions of
      intravenous drugs can be evaluated. The newly found properties of propofol, such
      as antiemetic, anticonvulsive and antioxidant, and its present clinical use are
      described. Finally, modern continuous intravenous anaesthetica techniques have
      been feasible only by the development of efficient application systems. The text
      gives an overview of the properties of modern syringe pumps and future
      developments of "smart" pumps.

PMID- 8580240
TI  - [Peculiarities of endotracheal intubation in the child].

PMID- 8580241
TI  - [Exposure of intensive care personnel to isoflurane in long-term sedation].
AB  - OBJECTIVE: Isoflurane is a suitable agent to produce sedation in the intensive
      care unit (ICU). However, data concerning occupational exposure to isoflurane
      during long-term sedation are not yet available. The purpose of this study was to
      evaluate occupational exposure to isoflurane in the ICU. DESIGN: Trace
      concentrations of isoflurane were measured directly by means of photoacustic
      infrared spectrometry during isoflurane sedation in ten cases over a period of 24
      hours. Values were obtained at four personnel-related and two leakage-related
      locations in an ICU chamber. RESULTS: All measured values were low, the majority
      under 3 ppm isoflurane at the personnel-related points. Peak concentrations up to
      40 ppm were recorded for several minutes during nursing interventions. At
      measurement point "nearby patient's mouth" values up to 5 ppm were recorded, at
      location "anaesthesia machine" values ranged from 2 to 69 ppm isoflurane.
      CONCLUSION: We conclude that an effective high flow scavenging system, a low
      leakage anaesthesia machine and an airconditioning equipment without
      recirculation could keep occupational exposure low. The majority of the measured
      values was below the NIOSH recommendation (2 ppm). All values was lower than a
      national state recommendation (10 ppm). Under other circumstances (e.g. without
      scavenging system) air pollution will be higher and therefore measurements at the
      working place are needed.

PMID- 8580242
TI  - [Anesthesiologic management in cardiomyoplasty].
AB  - Dynamic cardiomyoplasty is a therapeutic possibility in irreversible cardiac
      insufficiency. With this operation, the latissimus dorsi muscle is mobilised and
      drawn into the thorax where it is placed around the heart. Lateral and supine
      positioning as well as thoracotomy and direct manipulation of the heart are
      associated with particular risks during surgery. Eight patients with the
      diagnosis of cardiomyopathy underwent cardiomyoplasty. The patients were
      classified as NYHA III-IV. Continuous dobutamine infusions were routinely started
      after induction of anaesthesia. All patients were intubated with single-lumen
      tubes. After sternotomy, lidocaine was administered. Monitoring included Swan
      Ganz catheterisation and invasive blood pressure measurement. With early use of
      inotropic and vasodilatator agents the cardiac index and peripheral vascular
      resistance were adequately maintained. Double-lumen intubation seems to be
      unnecessary during cardiomyoplasty and only increases patient risk. Prophylactic
      lidocaine infusions are effective in preventing ventricular tachycardia and
      fibrillation. We conclude that adequate intraoperative management can improve the
      haemodynamic status of these patients so that cardiomyoplasty may be performed
      without significant morbidity.

PMID- 8580243
TI  - [Indications and technique of percutaneous dilatation tracheotomy for intensive
      care patients].
AB  - OBJECTIVE: Since the different techniques of percutaneous dilatational
      tracheotomy were introduced they have attracted particular attention in the
      intensive care setting. We present here a modification of the technique first
      described by Ciaglia in 1985. Objective of this study was to evaluate the
      frequency of complications of this modification in comparison with published
      data. METHODS: 151 dilatational tracheotomies were performed on 141 patients of
      an anaesthesiologic intensive care unit. Ciaglia originally presented an approach
      between the cricoid cartilage and the first tracheal cartilage. We found it
      preferable to insert the cannula between the 2nd and 3rd tracheal cartilage after
      blunt dissection of the pretracheal tissues. The Dilators of Cook Critical Care
      Ltd. were used in this study. RESULTS: With 151 tracheotomies only 11
      complications were noted: pneumothorax (1), bleeding (2), mucosal lesion of the
      trachea (2), others (6). None of these complications was considered to be
      serious. There was no tracheotomy-related death. Tracheotomy was performed within
      11.5 min (range 5 to 23 min). The duration of artificial ventilation following
      tracheotomy was 21.1 days (range 1 to 142 days). CONCLUSION: The presented
      modification of dilatational tracheotomy is a safe and effective technique which
      can be performed on the intensive care unit. Compared with conventional
      tracheotomy the new method is quickly done and will be an integral part of
      intensive care treatment.

PMID- 8580244
TI  - [Improved technique of dilatation tracheostomy and initial results].
AB  - Percutaneous dilatational tracheostomy is a simple bedside procedure and can be
      performed with a minimum of time and staff. Tears in the posterior wall of the
      trachea and paratracheal displacement of the tube are possible complications.
      These complications can be avoided by performing the procedure under
      bronchoscopic control. We report on 14 dilatational tracheostomies using this new
      technique. As a severe complication we noted bleeding from a vein with lethal
      blood aspiration in one case. Bleeding during dilatational tracheostomy procedure
      requires changing of technique and dissection of the anterior wall of the
      trachea.

PMID- 8580245
TI  - [Critical comments from the ENT physician viewpoint on Ciaglia percutaneous
      dilatative tracheostomy].

PMID- 8580246
TI  - [Intubation versus tracheotomy in long-term ventilation].

PMID- 8580247
TI  - [Prevention of stress ulcer in intensive care patients--contra].

PMID- 8580248
TI  - [Prevention of stress ulcer in intensive care patients--pro].

PMID- 8580249
TI  - [A 100-year-old transatlantic contribution to anesthesiologic quality control].
AB  - Aspects of quality assurance or control in anaesthesia were already discussed at
      the end of the last century. The reports "Zur Narkotisirungs-Statistik" given by
      the Berlin surgeon Gurlt between 1891 and 1895 are published examples. Answers in
      questionnaires and additional comments--mainly from German surgical hospital
      departments--were the main sources of these reports. However, every year some
      answers also came from foreign countries. In his fifth report Gurlt published in
      1895 the full text of a contribution given by Prince from Chicago, Illinois, USA.
      That report--given here once again in the original form--allows an insight into
      the practice of anaesthesia in North America in those days. Many of these
      statements and recommendations are still relevant; they are now essentials of the
      so-called "quality assurance" or "quality control".

PMID- 8580250
TI  - [Complications caused by patient positioning in unidentified "thoracic outlet
      syndrome"].
AB  - Following a 3-hour surgery of his left leg, a 22 year old male patient suffered
      paralysis and burning pain in his left forearm with numbness of his 3rd, 4th and
      5th finger. During the following days the symptoms diminished spontaneously. The
      explanation is an ischaemia due to the positioning during the operation in
      presence of an unknown thoracic outlet syndrome. Diagnostic procedure and
      prophylaxis of the disease are discussed.

PMID- 8580251
TI  - [Quality assurance in autologous blood donation. Introduction of a universal
      German language Site Master File].

PMID- 8580252
TI  - Cytocompatibility of calf pericardium treated by glutaraldehyde and by the acyl
      azide methods in an organotypic culture model.
AB  - Glutaraldehyde (GTA) is used to cross-link collagen-based biomaterials, but these
      materials are often cytotoxic. In order to overcome this problem, we have
      proposed the use of the acyl azide methods with either hydrazine or
      diphenylphosphoryl azide (DPPA) as reagents. In this paper we determine the
      cytocompatibility of acyl azide- and GTA-treated pericardium in vitro, by an
      organotypic chick aorta culture technique developed for the evaluation of the
      propensity of vascular cells (both endothelial and smooth muscle cells) to
      migrate and grow on the surface of biomaterials. We first examined pericardium
      stabilization as a function of GTA concentration and time, so that we could
      minimize residual GTA molecules in the material. Treatment for 72 h with 0.05%
      GTA was optimal for thermal stabilization of the pericardium with a denaturation
      temperature (Td) of 86.8 degrees C, providing similar results to treatment with
      0.6% GTA for 4 h (Td = 85.1 degrees C). Pericardium treated in this way was,
      however, poorly cytocompatible with little vascular cell migration and growth
      when compared with tissues treated by the acyl azide methods. The best results
      were obtained with 0.5% DPPA; treated tissues showed a high level of cross
      linking (Td = 82.4 degrees C) and three-fold increases in cell growth and
      migration over those in a non-toxic control.

PMID- 8580253
TI  - Application of enzyme immunoassays for testing haemocompatibility of biomedical
      polymers.
AB  - In this study enzyme immunoassays are presented for the assessment of platelet
      adhesion/activation and fibrinogen adsorption/conformation. The estimation of
      platelet adhesion and activation was performed with two enzyme immunoassays
      (EIAs) using monoclonal antibodies directed against CD42b (GP lb) and CD 62 (GMP
      140 or P-Selectin). The applicability of EIA was first demonstrated in microtitre
      plates coated with fibrinogen. The thrombogenic substrate showed that platelet
      adhesion and activation reached a plateau level within 30 min. The use of EIA for
      testing biomaterials was demonstrated with polymeric reference materials where a
      differentiation of materials with respect to adhesion and activation was
      achieved. To validate the EIA scanning electron microscopy was applied and
      confirmed the different extent of adhesion and activation of platelets on
      reference materials. In addition, polyurethaneureas, based on 4,4'
      diphenylmethane diisocyanate and polytetramethylene glycols, with different hard
      segment content and composition were investigated. It was found that both
      adhesion and activation were not simply dependent on the hard segment content but
      also on the hard segment composition. To get more insight into the mechanism of
      this process, two EIAs for the binding of fibrinogen using polyclonal and
      monoclonal antibodies were developed. There it was shown that the adhesion and
      activation of platelets on polyurethaneureas was not simply dependent on the
      total amount of adsorbed fibrinogen but rather on its conformation, indicated by
      the binding of the monoclonal antibody directed vs the gamma-chain of fibrinogen.

PMID- 8580254
TI  - Surface characterization and ex vivo blood compatibility study of plasma-modified
      small diameter tubing: effect of sulphur dioxide and hexamethyldisiloxane
      plasmas.
AB  - The development of a small diameter artificial vascular graft or prosthesis is
      limited by rapid thrombus formation and subsequent embolization upon blood
      contact. Plasma surface modification was employed to modify the inner surface of
      small diameter low density polyethylene (LDPE) tubing without varying the outer
      surface chemistry and physical properties of the tubing. A sulphur dioxide (SO2)
      plasma was used to form sulphonate functionality on the surface. In addition, a
      hexamethyldisiloxane (HMDSO) plasma and different gas flow ratios of SO2-HMDSO
      gas mixture plasmas were used to form ultrathin polysiloxane-like coatings inside
      the LDPE tubing. X-ray photoelectron spectroscopy (XPS) indicated that the inner
      surface of the tubing can be modified uniformly with this treatment. In addition,
      XPS results showed that the percentage of sulphur atoms bound to two or three
      oxygen atoms (sulphone or sulphonate) increased with the SO2-HMDSO mass flow rate
      ratio. The blood compatibility of the plasma-modified model materials was
      evaluated using an ex vivo canine arteriovenous shunt model. Similar
      thrombogenicity was observed comparing the untreated control and the surfaces
      modified by HMDSO plasma and SO2-HMDSO gas mixture plasmas, despite the
      differences in surface chemistry. The SO2 plasma-modified surface, which is the
      most hydrophilic as measured by the captive bubble contact angle measurement
      technique, was more thrombogenic than the untreated control. This may be
      attributed to the combined effect of the surface chemistry and surface
      hydrophilicity.

PMID- 8580255
TI  - Effect of antidenaturant drugs on lysozyme deposit formation on soft contact
      lenses by liquid chromatography--electrochemical detection.
AB  - The effect of some antidenaturant drugs on the formation of lysozyme deposits on
      soft contact lenses was investigated by in vitro experiments. Results were
      obtained which encourage the use of this strategy to reduce lens spoilage. At the
      same time emphasis is given to the possibility that some functionalities (i.e.
      lysine groups) present in drug molecules could promote protein adsorption. In
      order to evaluate at a quantitative level the effectiveness of the drugs used to
      minimize the formation of deposits on soft contact lenses, a selective method for
      the determination of adsorbed lysozyme was developed. It is based on the
      hydrolysis of the 'lens/adsorbed lysozyme' system, followed by high performance
      liquid chromatography coupled to electrochemical detection of the released
      tryptophan residues. The lysozyme calibration curve was linear up to 5 mg ml-1
      and the detection limit was 5 ng injected.

PMID- 8580256
TI  - Morphological changes in cultured human periodontal ligament cells exposed to
      dental materials.
AB  - The cytotoxicity of a range of dental restorative cements was assessed by
      continuous observation of cultures with inverted microscopy and by light
      microscopic study of fixed preparations, using an in vitro model with cultured
      test cells derived from human periodontal ligament. The sequential morphological
      changes observed over a seven day period showed different degrees of cell loss
      and patterns of injury in response to different restorative materials, reflecting
      primarily either nuclear or cytoplasmic damage. Attempts at recovery were
      frequently identified as the culture period was extended and were characterized
      by recolonization of denuded areas of the culture well. It was concluded that
      differing dental cements damage cells through a variety of mechanisms and that
      the test cells exhibit differing degrees of susceptibility to injury. Assays
      based on short-term cultures may overestimate cytotoxicity by not allowing for
      cell recovery from reversible injury or repopulation of monolayers by
      proliferation of resistant cells.

PMID- 8580257
TI  - Cutting directions of bone with biomaterials in situ does influence the outcome
      of histomorphometrical quantifications.
AB  - Ten commercially pure titanium implants were inserted in the tibia of ten mature
      New Zealand white rabbits for a healing period of 3 months. Cut and ground
      sections were performed on transversely and longitudinally cut tibia bone with
      implants in situ. Each implant with surrounding bone was processed by (a)
      dividing it into two parts by cutting transversely through the tibia and then (b)
      cutting one of the implant halves longitudinally through the tibia. In both cases
      10 microns sections were made. Computerized histomorphometrical calculations of
      the bone-to-metal contact and the bone area in the threads were performed and
      comparisons of the differently cut sections were made for the same implant.
      Larger amounts of bone-to-metal contact and bone area in the threads were
      observed in the longitudinally cut samples in comparison to transversely cut
      ones. A strong statistically significant difference was obtained when comparing
      the transversely with the longitudinally cut samples with respect to bony
      contacts in the cortical region, demonstrating 25% more bone-to-metal contact
      lengths in the longitudinal cutting direction of the tibia. Quantitative
      histomorphometrical comparisons should, therefore, be performed on samples that
      are cut in the same direction.

PMID- 8580258
TI  - Grafting of ethylene glycol-butadiene block copolymers onto dimethyl
      dichlorosilane-coated glass by gamma-irradiation.
AB  - Amphipathic ethylene glycol-butadiene block copolymers (PEG-PB) with different
      chain lengths of poly(ethylene glycol) (PEG) were synthesized by reacting
      poly(ethylene glycol methyl ether) (m-PEG, mol. wt = 350, 550, 750, 2000 and
      5000) with telechelic polybutadiene (PB). The PEG-PB copolymers formed were
      covalently grafted to dimethyldichlorosilane-coated glass (DDS-glass) by gamma
      irradiation. The PEG-grafted surface was characterized by measuring advancing and
      receding contact angles, fibrinogen adsorption, the number of adherent platelets
      and the area of spread platelets. The grafting efficiency was measured indirectly
      from the ability of the surface to prevent platelet adhesion. The total dose of
      gamma-irradiation necessary for grafting of PEG-PB onto DDS-glass in aqueous
      solutions was less than 0.24 Mrad at atmospheric pressure and ambient
      temperature. For successful grafting, the surface-adsorbed copolymers should be
      gamma-irradiated in the presence of water. gamma-Irradiation in the dried state
      did not result in copolymer grafting. The adsorption of copolymers for 30 min
      before exposure to gamma-irradiation was enough for effective grafting. The
      grafting was equally effective whether or not DDS-glass was exposed to the air
      copolymer solution interface when the DDS-glass was introduced into the copolymer
      solution. The copolymers were able to prevent platelet adhesion only when they
      were adsorbed onto DDS-glass at certain bulk concentrations. Too low or too high
      copolymer concentrations in the adsorption solution resulted in a surface where
      platelets could adhere and activate. The range of copolymer concentration which
      prevented platelet adhesion was larger as the PEG chain length of the grafted
      copolymers became longer. Our data indicate that platelet-resistant surfaces can
      be made by grafting PEG-PB onto chemically inert surfaces by a simple gamma
      irradiation process.

PMID- 8580259
TI  - Platelet and coagulation factor variations induced in vitro by polyethylene
      terephthalate (Dacron) coated with pyrolytic carbon.
AB  - The haemocompatibility of polyethylene terephthalate (Dacron) coated with
      pyrolytic carbon was examined in vitro, evaluating its capability of inducing
      adhesion and platelet activation, and of modifying the intrinsic coagulation
      pathway. Platelet adhesion was evaluated by counting platelets before and after
      in vitro contact of human plasma with the material under examination. Platelet
      activation was evaluated by determining platelet factor 4 (PF4) and thromboxane
      B2. Intrinsic coagulation pathway alterations were studied by determining
      activated partial thromboplastin time (APTT) and the activity of single factors.
      The results obtained show that pyrolytic carbon-coated Dacron induces platelet
      adhesion, reduction in platelet volume and lower increase in thromboxane
      production than that obtained after contact with uncoated Dacron. Pyrolytic
      carbon-coated Dacron does not induce PF4 release, contrary to uncoated Dacron
      induces a significant release. Moreover, pyrolytic carbon-coated Dacron, induces
      a significant extension of APTT by reducing the activity of intrinsic pathway
      factors, particularly factor XI.

PMID- 8580260
TI  - Effect of temperature on electrochemical deposition of calcium phosphate coatings
      in a simulated body fluid.
AB  - Calcium phosphate coatings were deposited on titanium plate by an electrochemical
      method in simulated body fluid at 5-62 degrees C. X-ray diffractometry and FTIR
      studies demonstrated that the deposits at 5, 22 and 37 degrees C were amorphous
      and those at 52 and 62 degrees C contained Mg(OH)2, CaCO3 and carbonate apatite
      of low crystallinity. The calcium, magnesium and phosphorus contents of deposit
      increased in direct proportion to the square root of loading time of cathodic
      potential. Induction periods, which might be thought to be the time required to
      decrease the pH of the electrolyte around the cathode by the formation of H2 gas
      and to start deposition of calcium phosphate, were observed on all the regression
      lines. It is concluded that in the electrochemical synthesis of calcium phosphate
      in this temperature range the diffusion process is a rate-determining step.

PMID- 8580261
TI  - Degradation-resistant character of synthetic hydroxyapatite blocks filled in bone
      defects.
AB  - The long-term changes of both the implanted hydroxyapatite (HA) blocks and the
      bone around them were observed radiologically to investigate the clinical
      usefulness of HA. HA blocks were used as a space filler in surgically created
      bone defects of seven cases due to curettage of bone tumours or removal for bone
      grafts, and they were followed up for 78 to 109 months. Bone formation around HA
      blocks peaked within 1 year after implantation, and then it faded gradually.
      However, shapes of HA blocks were rarely changed in all the cases. A clear zone
      around HA blocks was never observed . HA blocks were biocompatible and
      demonstrated a character resistant to degradation.

PMID- 8580262
TI  - In vitro biocompatibility testing of polymers for orthopaedic implants using
      cultured fibroblasts and osteoblasts.
AB  - The biocompatibility of two polymers for potential use as orthopaedic implant
      materials in an isoelastic hip prosthesis was investigated. The interactions of
      polyetheretherketone (PEEK) and epoxy resin polymers (with and without carbon
      fibre reinforcement) with both fibroblasts and osteoblasts were tested using cell
      protein, intracellular reduced glutathione (GSH), leakage of lactate
      dehydrogenase and the MTT assay as indices of cellular cytotoxicity. The epoxy
      resin polymer was slightly cytotoxic to and inhibited the growth rate of
      fibroblasts (as assessed by total cell protein), and depleted GSH in both cell
      types. In contrast, the PEEK material did not display overt signs of cytotoxicity
      and, in fact, increased osteoblast cell protein content. This suggests that, of
      these two materials, PEEK would be the one of choice for development of an
      isoelastic implant and, in view of its stimulatory effect on osteoblast protein
      content, it may encourage ingrowth of bone around the prosthesis and thus
      minimize joint loosening.

PMID- 8580263
TI  - Activation of the complement system by polysaccharidic surfaces bearing
      carboxymethyl, carboxymethylbenzylamide and carboxymethylbenzylamide sulphonate
      groups.
AB  - Substituted Sephadex derivatives bearing carboxymethyl (CM), CM-benzylamide
      (CMB), CM-propylamide (CMP) and CMB-sulphonate (CMBS) groups are used as models
      of polysaccharidic surfaces to measure the effects of substituting OH groups on
      the complement activating capacity (CAC) of the modified surfaces in normal human
      serum. CM substitution decreases and can suppress the CAC of Sephadex. Low CMB
      substitution also decreases the CAC, whereas high CMB or CMP substitutions
      increase it again after a minimum. In addition to C3 cleavage occurring at high
      substitution with CMB or CMP groups, the presence of CMB induces consumption of a
      protein, limiting CH50 measurements. The CAC variations could be due to
      rearrangements of the polymer surfaces at the aqueous interface with proteins.
      Highly substituted CMB-bearing surfaces could activate complement-like
      polystyrene surfaces. The presence of CMBS groups does not reduce the CAC of the
      surface. Such polymer surfaces, which are heparin-like concerning coagulation,
      are not heparin-like concerning complement inhibition.

PMID- 8580264
TI  - Review article: drug development in gastroenterology--the changing view of
      industry.
AB  - Rationalization within the pharmaceutical industry to combat escalating costs has
      included the close examination of research portfolios. Gastroenterology has been
      one of the casualties of this exercise and few companies currently retain a
      specific gastrointestinal research programme. Acid-peptic disease has been the
      victim of its own success, since the availability of a range of extremely
      effective drugs largely satisfies current medical needs. A safe, convenient and
      effective monotherapy able to eradicate Helicobacter pylori would be a
      commercially viable alternative to antisecretory drugs, leading to further
      expansion of the anti-ulcer market. The irritable bowel syndrome is probably too
      diverse a target for logical research: inflammatory bowel disease is probably too
      small a market to be attractive. Potentially effective drugs to treat these and
      other gastrointestinal diseases could emerge from broader research programmes,
      provided that companies retain the expertise and desire to develop such agents
      for gastrointestinal indications. Cancer of the gastrointestinal tract and
      associated organs undoubtedly represents a commercially attractive target, but
      new anti-tumour drugs are more likely to arise from generic research rather than
      programmes specifically directed at tumours of the gastrointestinal tract. The
      changing view of the pharmaceutical industry towards the development of
      gastrointestinal drugs is likely to have a negative impact on both fundamental
      and clinical research in gastroenterology.

PMID- 8580265
TI  - Review article: the risks of malignancy from either immunosuppression or
      diagnostic radiation in inflammatory bowel disease.
AB  - Inflammatory bowel disease is associated with an increased risk of
      gastrointestinal malignancy. There has been concern that either diagnostic
      medical radiation and long-term drug therapy--particularly immunosuppression-
      might contribute to this increased cancer risk. For the major drug groups (5
      aminosalicylates, steroids and immunosuppressants) data are scant but broadly
      reassuring. Only azathioprine (including 6-mercaptopurine) has been investigated
      at all carefully. Short- to medium-term therapy probably poses a very slightly
      increased risk of malignancy which is easily accepted given the current
      limitation of this agent to second-line use. Continuous therapy for more than two
      years is much less well documented, and caution should be maintained. A
      hypothetical model based on data from occupational radiation exposure has been
      constructed; this permits reasonable confidence that the medical use of ionising
      radiation contributes a negligibly increased risk of malignancy overall, and is
      particularly unlikely to add significantly to the incidence of gastrointestinal
      malignancy.

PMID- 8580266
TI  - Review article: artificial nutritional support for improved patient care.
AB  - Malnutrition is common and undiagnosed in the majority of affected hospital
      patients; it is associated with impaired organ function, morbidity, and increased
      length of hospital stay. Artificial nutritional support in malnourished patients
      leads to improvement in nutritional status and clinical outcome. Nutritional
      support is required in malnourished patients, patients who are unable to take
      normal diet and patients with intestinal failure. Gastroenterologists are
      required to supervise patients with intestinal failure, to insert endoscopic
      feeding devices, and increasingly to participate in, or lead, nutritional support
      teams. Major developments in nutrient delivery have included percutaneous
      endoscopic feeding devices, the recognition that enteral feeding is possible in
      patients with gastric stasis, and that nutrient needs can be met by peripheral
      parenteral nutrition. There is much interest in the use of new substrates, or
      substrates delivered in pharmacological doses such as glutamine and arginine, to
      manipulate the response to disease. Many hospitals lack an organized approach to
      artificial nutritional support. Patients continue to suffer from a lack of
      treatment or the consequences of inappropriate or inadequate treatment. This
      article reviews the current status of artificial nutritional support and provides
      guidelines for patient management.

PMID- 8580267
TI  - Helicobacter pylori eradication in a clinical setting: success rates and the
      effect on the quality of life in peptic ulcer.
AB  - BACKGROUND: Helicobacter pylori eradication for peptic ulcer has been widely
      taken up. Evidence for the efficacy of different regimens is often derived from
      small series in clinical trials but there is little reporting of everyday
      practice with unselected patients. Freedom from ulcer relapse has been
      demonstrated, but not whether this equates with clinical success. METHODS: We
      report on a series of 706 patients with H. pylori infection who, between January
      1991 and April 1995, received eradication therapy followed by assessment of H.
      pylori status. Two-hundred and seven of these patients were followed-up by postal
      questionnaire, validated by parallel questionnaires to their general
      practitioners, covering clinical outcome measures. RESULTS: The overall
      eradication rate was 81.7%, and a 1-week course of omeprazole plus two
      antibiotics was significantly better than a 2-week course of standard triple
      therapy (85.0% vs. 78.0%, P < 0.05). Amongst 21 first-time failures, a 7-day
      course of a clarithromycin-containing triple therapy succeeded in 18. The
      questionnaire replies indicate that, following successful H. pylori eradication,
      ulcer patients are less likely to consult with ulcer symptoms (P < 0.0005), take
      medication (P < 0.0005), require further prescription (P < 0.0005), or lose work
      time because of their ulcer (P < 0.005). They are more likely to have a
      subjective sense of ulcer cure (P < 0.0005). CONCLUSIONS: In addition to clear
      cost savings, social benefits are now demonstrated when H. pylori is eradicated.
      A well-tolerated 1 week regimen is genuinely effective in everyday practice.

PMID- 8580268
TI  - The effects of aminosalicylic acid derivatives on nitric oxide in a cell-free
      system.
AB  - AIMS AND METHODS: To determine the effect of aminosalicylic acid derivatives on
      the concentration of nitric oxide produced in a cell-free system, by the use of a
      sensitive and specific polarographic meter. RESULTS: The aminosalicylic acid
      derivatives 3-ASA (IC50 100 microM), 4-ASA (IC50 350 microM) and 5-ASA (IC50 5
      microM) all decreased the nitric oxide signal. These drugs had a similar
      inhibitory effect on the formation in vitro of nitrite from sodium nitroprusside
      (IC50: 200 microM, 500 microM and 100 microM, respectively). Sulphasalazine (31.1
      +/- 5% decrease in signal at 1 mM) was less effective than 5-ASA, but
      sulphapyridine, N-acetyl 5-ASA, indomethacin and hydrocortisone produced no
      decrease in nitric oxide signal at all. CONCLUSIONS: Nitric oxide binding may be
      part of the mechanism by which ASA derivatives exert their therapeutic effect,
      and this work suggests that it may be an important factor in the pathogenesis of
      ulcerative colitis.

PMID- 8580269
TI  - GR122311X (ranitidine bismuth citrate), a new drug for the treatment of duodenal
      ulcer.
AB  - BACKGROUND: Ranitidine bismuth citrate (GR122311X) is a new drug which offers
      potential benefits in healing duodenal ulcers and prevention of relapse. METHODS:
      This randomized, multi-centre double-blind study of 1620 patients compared the
      effect of 4 weeks of treatment with GR122311X 200 mg b.d. (n = 401), 400 mg b.d.
      (n = 404) or 800 mg b.d. (n = 404) or ranitidine hydrochloride 150 mg b.d. (n =
      411) on the rates of duodenal ulcer healing and of overall success (ulcers healed
      and remaining ulcer free in the 24-week follow-up phase). RESULTS: All four
      treatments were equally effective at ulcer healing (79%, 85%, 84% and 81% of
      patients, respectively). GR122311X 400 mg b.d. (38%) and 800 mg b.d. (37%) were
      significantly more effective than ranitidine hydrochloride 150 mg b.d. (32%) with
      respect to overall success (P = 0.050 and P = 0.030, respectively) but there was
      no difference with GR122311X 200 mg b.d. (31%). GR122311X caused effective, dose
      related suppression of H. pylori (47%, 61% and 74%); H. pylori eradication rates
      were 18%, 21% and 22%. GR122311X was safe and well tolerated, with an adverse
      event profile similar to that of ranitidine hydrochloride 150 mg b.d. Median week
      4 trough plasma bismuth levels were 1.3 ng/mL, 2.3 ng/mL and 3.3 ng/mL with
      GR122311X 200 mg b.d., 400 mg b.d. and 800 mg b.d. respectively. No individual
      plasma bismuth concentrations were of clinical concern. CONCLUSIONS: GR122311X is
      a safe and effective ulcer healing drug, and provides a platform on which anti-H.
      pylori therapy can be based.

PMID- 8580270
TI  - Effect of omeprazole and feeding on plasma gastrin in patients with achlorhydria.
AB  - BACKGROUND: The mechanism of hypergastrinaemia during omeprazole therapy is
      unclear, but is generally assumed to be entirely a consequence of acid
      suppression. However, direct stimulation of G cells by omeprazole could also be a
      factor. In order to further investigate the mechanism of omeprazole-induced
      hypergastrinaemia, we have studied the effects of the drug on plasma gastrin in
      patients with achlorhydria, in whom altered acid secretion cannot play a role.
      METHODS: We estimated fasting and peptone meal stimulated plasma gastrin in nine
      patients (seven female) with pernicious anaemia and achlorhydria, before and on
      the final day of 4 weeks' dosing with omeprazole 40 mg daily. RESULTS: Despite
      the high fasting gastrin concentrations, the peptone meal produced a further
      elevation in plasma gastrin concentrations, median gastrin concentrations rising
      from 1500 ng/L (range 225-10,875 ng/L) to 3750 ng/L (range 585-15,600 ng/L) post
      prandially (P = 0.004). The median post-prandial rise in plasma gastrin at this
      initial visit was 44% (3-260%), and the median time interval until plasma gastrin
      concentrations returned to fasting levels was 120 min (range 10- > 150 min).
      There was a significant negative correlation between fasting plasma gastrin
      concentrations and the percentage increase in plasma gastrin levels in response
      to meal stimulation (Spearman correlation coefficient -0.79, P = 0.01). Fasting
      plasma gastrin concentrations were similar pre-omeprazole (median 1950 ng/L,
      range 240-16,500 ng/L) and post-omeprazole (median 1500 ng/L, range 315-7650
      ng/L). Likewise, peak plasma gastrin concentrations were also similar pre
      omeprazole (median 2700 ng/L, range 585-16,500 ng/L) and post omeprazole (median
      3420 ng/L, range 720-11,250 ng/L). CONCLUSIONS: (i) The hyperplastic G cell mass
      in patients with pernicious anaemia can be further stimulated by a peptone meal,
      which causes a prolonged rise in plasma gastrin concentrations. (ii) There is a
      negative correlation between fasting plasma gastrin concentrations and the
      percentage increase in plasma gastrin levels in response to meal stimulation.
      (iii) Omeprazole has no effect on plasma gastrin in achlorhydric patients, which
      is consistent with its hypergastrinaemic effect being entirely secondary to acid
      inhibition.

PMID- 8580271
TI  - Addition of metronidazole to omeprazole/amoxycillin dual therapy increases the
      rate of Helicobacter pylori eradication: a double-blind, randomized trial.
AB  - AIMS: To compare the efficacy, safety and tolerability of an
      omeprazole/amoxycillin (OA) dual therapy Helicobacter pylori eradication regimen
      with an omeprazole/amoxycillin/metronidazole (OAM) triple therapy regimen.
      METHODS: In this double-blind trial, conducted in 19 hospitals, 119 patients with
      symptomatic duodenal ulcer disease were randomized to receive either 14 days
      treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and placebo
      followed by a further 14 days' treatment with omeprazole 20 mg daily (n = 59) or
      14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s., and
      metronidazole 400 mg t.d.s., followed by a further 14 days' treatment with
      omeprazole 20 mg daily (n = 60). H. pylori status was assessed by 13C-urea breath
      test at entry and at 4 weeks post-treatment. RESULTS: H. pylori infection was
      eradicated in 46% of the OA treated patients and in 92% of the OAM treated
      patients, a mean difference of 46% (P < 0.0001, 95% CI for the difference: +30 to
      +62). In only one patient was the duodenal ulcer not endoscopically healed after
      4 weeks of treatment (OA 100%; OAM 98% healed). There were no significant
      differences in speed of symptom relief or improvement in symptoms between the two
      groups. Both regimens were well tolerated, with 96% of patients completing the
      course, and only one patient withdrawing due to an adverse event. The only side
      effect with a significantly higher incidence in the OAM group was diarrhoea,
      which occurred in 36% of patients compared to 16% of patients in the OA group (P
      < 0.05). CONCLUSIONS: A regimen consisting of omeprazole 40 mg daily, amoxycillin
      500 mg t.d.s. and metronidazole 400 mg t.d.s. for 14 days gives an appreciably
      higher H. pylori eradication rate than omeprazole and amoxycillin alone, with
      acceptable tolerability.

PMID- 8580272
TI  - A comparison of three doses of lansoprazole (15, 30 and 60 mg) and placebo in the
      treatment of duodenal ulcer. The Lansoprazole Study Group.
AB  - BACKGROUND: Lansoprazole is a new proton pump inhibitor for the treatment of
      peptic ulcer disease. METHODS: A double-blind, multicentre study was undertaken
      in 296 patients with endoscopically proven duodenal ulcer to compare the efficacy
      and safety of lansoprazole 15, 30 or 60 mg with placebo. Ulcer healing was
      documented by endoscopy at 2 and 4 weeks; patients whose ulcers healed after 4
      weeks were followed for up to 6 months post-treatment. RESULTS: Four-week healing
      rates of 89.4%, 91.7% and 89.9% were obtained with lansoprazole 15, 30 and 60 mg,
      respectively, compared with 46.1% on placebo (P < 0.001). All three doses of
      lansoprazole produced rapid symptom relief, although patients taking 60 mg
      lansoprazole required fewer antacids than did those taking 15 mg. At 6 months,
      the percentages of patients healed were 45.3%, 40.0% and 38.4% in the
      lansoprazole 15, 30 and 60 mg dosage groups, respectively, and 25.3% for the
      placebo group. No significant adverse events were documented during the period of
      this trial. CONCLUSION: Lansoprazole is an effective and safe treatment for
      duodenal ulcer and the 15 mg dose is as effective as 30 or 60 mg.

PMID- 8580273
TI  - Erythromycin shortens orocaecal transit time in diabetic male subjects: a double
      blind placebo-controlled study.
AB  - BACKGROUND: The effects of erythromycin on small bowel motility are
      controversial. Orocaecal transit time (OCTT) is considered to be a valid measure
      of small bowel motility. METHODS: We studied the effect of erythromycin on OCTT
      in diabetic male subjects in a double-blind placebo-controlled crossover fashion.
      After an overnight fast, subjects received erythromycin 500 mg, 250 mg or
      placebo, on 3 different days. A standard solid meal containing 20 g lactulose was
      administered 30 min after the erythromycin ingestion. Exhaled breath was
      collected and hydrogen concentration was assessed over 5 h. Breath hydrogen
      concentrations for each session were analysed over time by a generalized logistic
      function generating a sigmoidal curve. Front transit time was recorded as the
      time point when a sustained rise in breath hydrogen concentration of at least 5
      p.p.m. was first observed. RESULTS: The mean +/- S.E.M. time taken for the front
      of the meal to reach the caecum was 92.5 +/- 9.5, 86.1 +/- 16.5 and 62.3 +/- 12.1
      min for placebo, erythromycin 250 mg and erythromycin 500 mg, respectively. The
      OCTT was significantly decreased with erythromycin 500 mg compared to placebo (P
      < 0.05). CONCLUSION: Oral administration of 500 mg erythromycin has prokinetic
      effect on orocaecal transit in male patients with diabetes mellitus.

PMID- 8580274
TI  - Treatment of hepatitis B surface antigen carriers in the early stage of the
      infection using recombinant alpha-interferon with steroid priming.
AB  - BACKGROUND: Alpha-interferon has been found to inhibit hepatitis B virus (HBV)
      replication in Chinese patients with chronic HBV infection although a sustained
      effect was rarely achieved in those with normal pretreatment serum alanine amino
      transferase (ALT) levels. Prednisolone priming has been found to be beneficial
      over treatment with interferon alone in these subjects. We studied the effect of
      steroid pre-treatment followed by recombinant interferon alpha-2a in the
      treatment of asymptomatic HBV carriers with positive hepatitis Be antigen
      (HBeAg), hepatitis B viral DNA (HBV-DNA) and minimal changes in liver histology.
      METHODS: The treatment regimen included a 6-week prednisolone priming, a 2 week
      rest followed by 14 weeks of three times weekly 9 mega units of interferon alpha
      2a injection and 52 weeks of follow-up. There were seven patients in the
      treatment group and seven controls. RESULTS: The mean age, pre-treatment ALT
      (normal in all except for one in each of the treatment and control groups), HBV
      DNA levels and histological scores were similar in the two groups. Serum HBV-DNA
      levels fell in six patients during treatment and became undetectable in two of
      them by the end. During follow-up, serum HBV-DNA returned to pre-treatment levels
      in all patients. None of the treated patients had HBeAg sero-conversion and none
      of the controls had spontaneous clearance of HBV-DNA or sero-conversion of HBeAg.
      No improvement of liver histology was observed in any of the treated patients.
      There were only mild flu-like side-effects noted and interferon alpha-2a was well
      tolerated at the doses given among treated patients. CONCLUSION: Prednisolone
      priming followed by interferon alpha-2a treatment has no beneficial effect on HBV
      carriers in the early stages of chronic hepatitis B infection.

PMID- 8580275
TI  - Lipocortin-1 autoantibody concentration in children with inflammatory bowel
      disease.
AB  - BACKGROUND: Corticosteroids are widely used to treat children with inflammatory
      bowel disease although the response is variable, side-effects are common, and
      many patients develop a partial or complete steroid resistance. The mechanism
      underlying these phenomena are unclear. Corticosteroids mediate some of their
      actions through lipocortin-1, and the induction of autoantibodies to lipocortin
      has been proposed as a possible mechanism by which steroid efficacy is suboptimal
      in vivo. PATIENTS AND METHODS: We have measured serum lipocortin-1 antibody
      concentration by ELISA in 38 children with Crohn's disease, 12 with ulcerative
      colitis and in 15 controls. RESULTS: IgG and IgA anti-lipocortin-1 antibody
      levels were higher in the Crohn's group than in the ulcerative colitis or control
      groups. Elevated concentrations did not relate to disease activity, history of
      steroid therapy or steroid-responsiveness. Lipocortin IgM antibody status was
      similar in all three groups. CONCLUSION: It is therefore unlikely that serum
      antibodies to lipocortin-1 have a role in the development of steroid-resistance
      in children with inflammatory bowel disease.

PMID- 8580276
TI  - The effect of treatment on lymphokine-secreting cells in the intestinal mucosa of
      children with Crohn's disease.
AB  - BACKGROUND: Recent studies have shown both interleukin 2 (IL-2) and interferon
      gamma (IFN) to be elevated in patients with active Crohn's disease compared to
      ulcerative colitis or non-inflammatory bowel disease controls. However the effect
      of treatment on these lymphokines has not been studied. PATIENTS AND METHODS:
      Using a reverse haemolytic plaque assay the percentage of lymphokine-secreting
      cells was determined in the intestinal mucosa of children with Crohn's disease
      before and after 8 weeks of treatment with either enteral nutrition, cyclosporin
      or steroids. RESULTS: Before treatment, a high percentage of cells isolated from
      mucosal biopsies secreted IL-2 or interferon-gamma. Eight weeks' treatment with
      the immunosuppressive agents cyclosporin, or with corticosteroids, produced a
      significant reduction in the percentage of IL-2 secreting cells, although only
      for the former was there also a reduction in interferon-gamma secreting cells.
      Enteral nutrition however, produced a reduction in lymphokine-secreting cells
      equivalent to cyclosporin and produced the best histological and clinical
      improvement. CONCLUSION: Enteral nutrition and cyclosporin can down-regulate
      lymphokine secretion in the gut in Crohn's disease.

PMID- 8580277
TI  - Prospective study of fluconazole suspension for the treatment of oesophageal
      candidiasis in patients with AIDS.
AB  - BACKGROUND: Oesophageal candidiasis is the most common cause of oesophageal
      symptoms in patients with AIDS. Antifungal therapy, given as a suspension, may be
      better tolerated than capsules or tablets in children or patients with
      oesophageal symptoms. We performed a prospective study of the safety and efficacy
      of fluconazole suspension. METHODS: Patients with HIV infection; odynophagia,
      dysphagia, or retrosternal pain; endoscopic evidence of white plaques or exudate
      in the oesophagus; and microscopic confirmation of fungal infection on biopsy or
      brushing specimens were eligible. Patients received fluconazole oral suspension
      (200 mg loading dose followed by 100 mg q.d.s.). Therapy was continued for 2
      weeks after symptom resolution. Repeat endoscopy was performed after completion
      of therapy. RESULTS: Forty-two patients enrolled in the study: 40 were male, mean
      (+/- s.e.) age was 37 +/- 2 years and mean CD4 cell count was 67 +/- 14/mm3. One
      patient was not evaluable because he received amphotericin during the first week
      of therapy. Symptoms resolved in all 41 evaluable patients; 17 (41%) had
      resolution by 1 week, 37 (90%) by 2 weeks, and 40 (98%) by 3 weeks. Endoscopic
      resolution occurred in 35 (95%) of 37 patients who underwent repeat endoscopy.
      Adverse events (skin rash in 1, nausea/vomiting in 2, elevated liver tests in 2)
      led to early termination of therapy in 5 patients, all of whom had clinical and
      endoscopic cure. CONCLUSIONS: Symptoms resolved in 100% of patients with AIDS and
      oesophageal candidiasis receiving an oral suspension of fluconazole, and 90% of
      patients had symptom resolution within 2 weeks. Determining whether the more
      rapid clinical cure in this study, compared with a previous trial which employed
      capsules, is related to an additional topical antifungal effect of the
      suspension, will require further study.

PMID- 8580278
TI  - Comparison of budesonide and 5-aminosalicylic acid enemas in active distal
      ulcerative colitis.
AB  - BACKGROUND: Budesonide is a new corticosteroid with high topical anti
      inflammatory activity but little systemic effect. The aim of the present study
      was to compare the efficacy and safety of budesonide enema (2 mg/100 mL) and 5
      ASA enema (mesalazine 1 g/100 mL) given for 4 weeks in the treatment of active
      distal ulcerative colitis and proctitis. METHODS: Ninety-seven patients were
      studied in a multicentre single-blind randomized group-comparative trial. The
      primary efficacy variables were endoscopy and histopathology scores obtained at
      0, 2 and 4 weeks. Clinical symptoms were the secondary efficacy variables.
      Haematology, chemistry and adverse events were the safety variables. RESULTS:
      Budesonide and 5-ASA enemas both resulted in a significant improvement in
      endoscopy and histopathology scores but no difference could be demonstrated
      between the two treatment groups. There was also a significant improvement of
      symptoms (number of bowel movements per day, quality of stools, presence of blood
      and mucus, and state of well-being) within both groups but no difference between
      the two treatment groups. The clinical remission rate at 4 weeks was, however,
      38% for patients treated with budesonide enema but 60% for those treated with 5
      ASA enema (P = 0.03). No adverse events attributed to the study drugs were
      recorded in either of the groups. CONCLUSIONS: Budesonide enema 2 mg/100 mL
      appears to be as efficient and well-tolerated as 5-ASA enema in the treatment of
      active distal ulcerative colitis and proctitis.

PMID- 8580279
TI  - The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility.
AB  - AIM: To evaluate the effects of various doses of lintopride, a new 5HT-4
      antagonist with moderate 5HT-3 antagonist properties, on oesophageal body and
      lower oesophageal sphincter (LOS) motility in humans. METHODS: Eight healthy male
      volunteers, mean age 22 (19-28) years, without any history of digestive disease
      or chest pain, were randomized to three doses of lintopride (0.1, 0.3 and 0.5
      mg/kg i.v.) and a placebo at 1-week intervals in a double-blind, crossover study.
      Oesophageal motility was recorded continuously for 4 h after each dose, using
      perfused catheters inserted at the level of the LOS and in the body of the
      oesophagus, at 5, 10 and 15 cm from the LOS. Peristalsis was studied during 10
      wet swallows, at 30-min intervals (T0-T240 min). RESULTS: The LOS basal pressure
      (23.3 +/- 2.0 cmH2O; mean +/- s.d.) remained stable after dosing with placebo to
      T240. After lintopride, LOS basal pressure increased significantly vs. placebo
      (AUC comparison: 0.1 mg/kg, P = 0.036; 0.3 mg/kg, P = 0.027; 0.5 mg/kg, P =
      0.052). In contrast, the duration and extent of LOS relaxation after swallowing
      was not affected by any of the three doses of lintopride. The amplitude of
      peristaltic waves in the oesophagus increased significantly at T30 after
      lintopride 0.3 mg/kg (34.5 cmH2O, P = 0.020) and 0.5 mg/kg (32.5 cmH2O, P =
      0.027), at T60 after 0.3 mg/kg (48.8 cmH2O, P = 0.0009) and 0.5 mg/kg (29.1
      cmH2O, P = 0.029) and at T90 after 0.3 mg/kg (34.5 cmH2O, P = 0.0018).
      CONCLUSIONS: Lintopride significantly increased the LOS basal tone without
      affecting LOS physiological relaxation after swallowing. Peristaltic waves were
      also enhanced by lintopride.

PMID- 8580280
TI  - Patterns of 24-hour oesophageal acid exposure after acute withdrawal of acid
      suppression.
AB  - AIM: To measure 24-h ambulatory oesophageal pH data in patients with gastro
      oesophageal reflux disease prior to, during and after acute treatment with
      comparable doses of omeprazole and ranitidine. METHODS: The subjects were 20
      adults with at least 8% acid contact time. Ten subjects were treated for 1 week
      with omeprazole 20 mg q.d.s. and 10 subjects with ranitidine 300 mg t.d.s. All
      subjects were examined at the end of 1 week of therapy and subsequent to
      cessation of treatment (1 day for ranitidine and 3 days for omeprazole). RESULTS:
      Both drugs produced a statistically significant (P < 0.05) decrease in acid
      contact time with acute treatment. Omeprazole produced a significantly greater
      decrease in acid contact time when compared to ranitidine. Subsequent to
      treatment cessation, the total acid contact time for omeprazole remained
      significantly less than the baseline level, while ranitidine returned to levels
      which were not significantly different from the baseline. CONCLUSION: These data
      provide no evidence for a 'reflux rebound' subsequent to the cessation of acute
      acid secretory suppression.

PMID- 8580281
TI  - Do non-steroidal anti-inflammatory drugs have an effect on gastric cell turnover?
AB  - AIM: To study the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on
      gastric cell turnover using an in vitro immunohistochemical method of
      bromodeoxyuridine (BrDU) uptake. METHODS: Thirty patients undergoing routine
      upper gastrointestinal endoscopy were studied. Sixteen had taken NSAIDs daily for
      more than 3 months and there were 14 age-matched controls. Endoscopic gastric
      antral biopsies were obtained and stained immediately using the BrDU technique.
      Cell proliferation was expressed as a labelling index percentage (LI%) defined as
      the number of BrDU-labelled nuclei in 10 gastric glands, expressed as a
      percentage of the total cells in the gastric gland. RESULTS: Gastric infection
      with Helicobacter pylori was excluded in all patients. Of the 16 patients on
      NSAIDs, four had gastritis, four had erosions or ulceration and eight had a
      normal examination. Endoscopy was normal in all patients in the control group.
      The LI% (mean +/- S.E.M.) in the entire NSAID group was 4.09 +/- 0.29 and in the
      control group 3.57 +/- 0.29. No significant difference was observed. In the NSAID
      patients with gastritis and erosions or ulceration, the LI% was 4.99 +/- 0.61 and
      3.07 +/- 0.32, respectively. There was no significant difference in LI% between
      the endoscopic subgroups of patients on NSAIDs or between patients on NSAIDs who
      had normal endoscopy and the control patients. CONCLUSION: These results provide
      evidence that refutes the hypothesis that the prevalence of NSAID gastropathy is
      due to an effect on gastric cell turnover.

PMID- 8580282
TI  - Use of somatostatin and its long-acting analogue, octreotide, in the treatment of
      pancreatic diseases.

PMID- 8580283
TI  - [Periodogram analysis for signal and noise evaluation in roentgen video signals].
AB  - Movements of the heart, the large vessels and the gastrointestinal tract can be
      evaluated for diagnostic purposes using fluoroscopic video systems. A new means
      of quantitatively evaluating the signal and noise components of the video signal
      is described. The signal and noise power components are determined from the
      periodogram after prior Fourier analysis. Variance is reduced by averaging and
      keeping the measuring conditions constant. For measurements of signal transfer
      properties, a radiological phantom capable of producing sinusoidal movements of
      the edge of the object was developed. An analysis of the performance of the
      theoretically derived evaluation parameters was carried out at a fluoroscopic
      unit under clinical conditions. Periodogram analysis makes possible objective
      image quality evaluation in clinical motion studies and in the technical quality
      assurance of fluoroscopic video systems. The use of a compact PC-based video
      measuring system renders application both practical and easy.

PMID- 8580284
TI  - [Phase portraits of transfer systems--detection of nonlinear transmission
      properties between respiratory movements and heart rate fluctuations].
AB  - A new approach to the analysis of non-linear systems is proposed. It enables the
      reconstruction of the system state movement in a multi-dimensional phase space.
      The resulting phase portraits of the system behaviour were characterised
      quantitatively by estimating the correlation dimensions and prediction errors.
      This new approach was validated using simulated typical transfer systems. The
      measured respiratory movements and heart rate fluctuations of rabbits were
      employed for the first time to investigate the non-linear transfer properties
      between respiratory activity and heart rate in the system phase portraits.
      Significant non-linear transfer characteristics between respiratory movements and
      heart rate fluctuations were found--also during the awake phase--which have so
      far not been quantified.

PMID- 8580285
TI  - [Adaptive algorithm for automatic measurement of retinal vascular diameter].
AB  - A new adaptive computer-aided method for the measurement of blood vessel
      diameters has been developed. Within areas of interest in the image, the
      algorithm detects, line-wise, the edges of the vessels, which are then used for
      image-wise approximation and noise filtration. A high level of adaptivity with
      respect to numerous measuring parameters ensures its use in a wide range of
      applications. Thus, it has been shown to significantly improve clinically
      relevant reproducibility in the area of follow-up observations. The standard
      deviation for vessel diameter was (2.2 +/- 0.7)% in the case of arteries and (1.8
      +/- 0.5)% in the case of veins. Testing the algorithm in images of poor quality
      revealed its high level of reliability and sensitivity.

PMID- 8580286
TI  - Event-related coherence during finger movement: a pilot study.
AB  - Dynamic functional coupling between contralateral sensorimotor and supplementary
      motor areas during unilateral finger movements is studied using event-related
      coherence analysis. It is demonstrated in 3 subjects that the intrinsic rhythm of
      the sensorimotor area (mu rhythm) is phase coupled to intrinsic rhythmic activity
      of the supplementary motor area during rest. With preparation and execution of
      discrete, unilateral finger movements, these intrinsic rhythms are desynchronized
      due to activation of each of the local cortical networks, and the degree of
      synchrony or phase consistency between these rhythms decreases.

PMID- 8580287
TI  - [Signal smoothing and differentiation with a single operator].
AB  - For the filtering and subsequent processing of of very noisy force curves
      obtained in studies of isolated heart muscles, an operator derived from the rules
      used in the construction of Bezier curves has been tested. The advantage of using
      the latter is that despite major changes in one sample as compared with another,
      the resulting curve changes only slightly. The derived operator permits either
      smoothing only or can be extended for both smoothing and differentiation
      simultaneously. With the filtering operation "smoothing and differentiation",
      even very noisy signals can be successfully processed. The operator is
      insensitive to signal interference and has advantages in terms of speed and
      complexity.

PMID- 8580288
TI  - [Increasing the safety of ceramic femoral heads for hip prostheses].
AB  - Since 1974 Biolox ceramic femoral ball heads have been used successfully for
      artificial modular hip joints. The revision rate due to ball head fracture is
      lower than 0.02%. This is an extremely low value. In this article it is shown how
      the safety of a ceramic ball head can be improved using the procedures of HIPing,
      engraving by laser technique, and 100% proof testing. By applying these means the
      materials properties density, grain size, grain size distribution, and the
      strength of the ball head, i.e. the fracture load can be improved significantly.

PMID- 8580289
TI  - [15 years experience with the Ti-6Al-7Nb alloy for joint prostheses].
AB  - The Ti-6Al-7Nb alpha-beta alloy, Protasul-100 was developed between 1978 and
      1982, and proved to be highly biocompatible. In 1985 the TiAlNb material was
      approved for clinical use. Over the last ten years, more than 200 tons of semi
      finished bar material has been processed, mainly for the production of cementless
      femoral stem systems and elastically deformable cup shells. For uncemented
      femoral components of knee prostheses made of TiAlNb, a special oxygen diffusion
      hardening process was developed that enables a surface hardness of up to 1200 HV
      and 600 HV at a depth of 20 microns, as compared with 350 HV in the case of the
      TiAlNb base material. This ODH-treated, polished surface is extremely scratch and
      wear resistant, and forms a good articulating surface with UHMW polyethylene.
      This surface-hardened TiAlNb, Tribosul, has been in clinical use in femoral knee
      components since 1990, and a multicentric clinical study involving femoral heads
      for hip prostheses has been ongoing since 1992. These different applications in
      hip and knee joint prostheses may suffice to demonstrate that the custom-made Ti
      6Al-7Nb alpha-beta alloy is a real alternative to the well-known Ti-6Al-4V alloy,
      which has been used for decades as an implant material. Both national and
      international standards are available, and the alloy was already approved by the
      FDA in 1987.

PMID- 8580290
TI  - [Materials for hip endoprostheses--alternatives to standard materials].
AB  - A review of current clinically applied biomaterials for the femoral heads and
      acetabular cups of total hip prostheses (UHMWPE, CoCrMo alloys, alumina and
      zirkonium) in terms of their resistance to wear is presented. Further
      developments in metallic and ceramic materials over the last few years have now
      left UHMWPE as the weakest link in the prosthesis material chain. Alternative
      materials aimed at improving the tribological properties of the femoral
      head/acetabular head system are presented. New surface hardening and coating
      techniques for titanium alloys, polymer coatings, optimized UHMWPE, as well as
      various carbon-fibre-reinforced synthetic materials are described. The
      advantages, disadvantages and prospects of these materials are compared with
      those of standard materials and documented in experimental and clinical studies.

PMID- 8580291
TI  - [Integrated gait analysis: a complex expert system approach to detailed data
      evaluation].
AB  - Integrated Gait Analysis is still not accepted as an important tool in a routine
      clinical environment because of its lack of assessment procedures closely based
      on the raw data measurements. Furthermore, an adequate treatment of the complex
      process of human movement is missing. This contribution is intended to
      successively describe the scheme of a dedicated approach for gait analysis data
      assessment. Therein, different technologies already discussed in the literature
      have been used. Some examples are given for the purpose of illustration. To
      provide in advance sufficiently different and well-known measurement conditions,
      extreme manipulations in the alignment of below-knee prostheses have been carried
      out. It is shown that some specific data formats consisting of subgroups of gait
      patterns have turned out to be important for further partial processing and for
      interfacing the different subsystems. However, due to data characteristics of the
      raw data and the lack of a well-founded a priori knowledge, some principal
      questions have to be left open. Therefore, on the basis of the different results
      presented below and their discussion, a more detailed model of the process is
      proposed for further research following this concept.

PMID- 8580292
TI  - [Evaluating an interactive, multi-media learning system for the study of primary
      open angle glaucoma].
AB  - Using the interactive multimedia learning system for studying open-angle glaucoma
      [3] a prospective, randomized, case-controlled study was carried out to determine
      the value of this new form of learning in terms of acceptance and the imparting
      of knowledge. This article describes details of the study and presents their
      results. Results were established on the basis of targeted questions asked prior
      to and after the learning phase, followed by an analysis of frequencies and
      significance testing by the Chi squared method. It was shown that the imparting
      of knowledge is significantly improved when this learning system is employed. In
      addition, after its first use, acceptance of this new medium rose dramatically.

PMID- 8580293
TI  - Olive oil and breast cancer.

PMID- 8580294
TI  - Mass screening for cervical cancer in Norway: evaluation of the pilot project.
AB  - The Norwegian Department of Health and Social Affairs initiated a national
      screening program for cervical cancer in 1990, with all women aged 25 to 70 years
      to be offered cervical screening every three years. During the first three years
      of the program (November 1991-October 1994), all spontaneous cervical cytology in
      Norway was recorded at the Norwegian Cancer Registry. In addition, women in the
      counties of Vestfold and Sor-Trondelag were invited individually to be screened.
      The aim of the present study was principally to evaluate the organization aspects
      of a nationwide, population-based screening program for cervical cancer in
      Norway. Special attention was paid to the coverage, the attendance rate, and the
      cytologic findings in the two-county study area. A total of 1,581,379 Pap smears
      were recorded from November 1991 to October 1994. Most smears were taken from
      women under age 30 years (31.7 percent). About 25 percent of the women aged 25 to
      29 years had more than one normal smear. In the study area, a coverage of about
      71 percent in the age group 25 to 69 years was achieved. The pilot project also
      has shown that it is possible to recruit elderly women into screening. However,
      no difference was noted between the study and the reference area with regard to
      findings per smear of precursor lesions (CIN 3, modified SNOMED coding system).
      The experiences from three years of recording and the implementation of the pilot
      project have provided useful guidelines for the national screening which began in
      January 1995.

PMID- 8580295
TI  - Oral contraceptive use and risk of breast cancer in older women (New Zealand).
AB  - The effect of oral contraceptive (OC) use at older ages on the risk of breast
      cancer was examined in a national population-based case-control study conducted
      in New Zealand. A total of 891 women aged 25 to 54 years with a first diagnosis
      of breast cancer, and 1,864 control subjects, randomly selected from the
      electoral rolls, were interviewed. The relative risk (RR) of breast cancer for
      women aged 45 to 54 years at diagnosis who had ever used OCs was 1.0 (95 percent
      confidence interval [CI] = 0.77-1.3). There was no significant increase in risk
      of breast cancer among recent users of OCs of any age. Analyses according to age
      at first and last use among women aged 40 years and older at diagnosis showed no
      group with an elevated risk of breast cancer. Women who had used OCs for 10 years
      or longer after age 40 had an apparent increase in risk (RR = 2.7, CI = 0.97
      7.5), but the trend in risk with duration of use was not significant. These
      findings suggest that OC use in older women does not affect their risk of breast
      cancer appreciably, but it is not possible to rule out a modest increase in risk
      with such use.

PMID- 8580296
TI  - Prostate cancer: trends in mortality and stage-specific incidence rates by
      racial/ethnic group in Los Angeles County, California (United States).
AB  - Between 1976 and 1988 in the United States, the secular trends to age-adjusted
      incidence rates of prostate cancer were significantly different by racial/ethnic
      group (P < 0.001), and increased significantly only among non-Hispanic Whites at
      a rate of 2.7 percent (95 percent confidence interval [CI] = 2.3-3.1%) annually.
      While incidence rates of regional disease increased significantly (7.7 percent to
      11.3 percent annually) among all racial/ethnic groups during this period,
      localized disease increased significantly only among non-Hispanic Whites, by 1.8
      percent (CI = 1.4-2.3%) annually. Prostate cancer mortality in Los Angeles County
      (California) remained constant among Hispanics, non-Hispanic Whites, and Asians,
      but increases 1.6 percent (CI = 0-3.2%) annually among Blacks. While the increase
      in localized disease rates of non-Hispanic Whites may be due to increased
      detection of asymptomatic disease, this apparently has not occurred among other
      racial/ethnic groups in Los Angeles County. The secular increase in regional
      disease rates among all racial/ethnic groups without a concurrent increase in
      mortality (except Blacks), suggests increased accuracy of staging rather than a
      true increase in incidence may account for these trends. Adjusted for
      socioeconomic status, year and age at diagnosis, Black and Hispanic men were at
      significantly higher risk of being diagnosed with non-localized disease (odds
      ratio = 1.39 and 1.24, respectively) than were non-Hispanic Whites.

PMID- 8580297
TI  - Reproducibility of recall of adolescent diet: Nurses' Health Study (United
      States).
AB  - Although diet and alcohol consumption at a younger age have been hypothesized to
      play an etiologic role in adult malignancy, few studies have addressed these
      relations and few data exist on the ability to measure recalled diet during
      adolescence. We undertook a study to determine whether the recall of diet during
      high school 22 to 47 years later was reproducible within a prospective cohort of
      women. In 1986, participants in the Nurses' Health Study (United States), aged 40
      to 65 years, reported their diet during high school using a 24-item food
      frequency questionnaire (FFQ). On the 1988 questionnaire, the participants
      recorded their alcohol consumption between the ages of 18 and 22. In 1994, a
      random sample of 275 women were asked to record again their high school diet and
      alcohol consumption. The average of Spearman correlations between the two recalls
      of high school diet was r = 0.57 (range = 0.38 to 0.74). For alcohol intake, the
      correlation for the time period queried was 0.66. The correlation between the two
      recalls of high school diet was higher than the correlation between the first
      recall and current diet in 1986 (average r = 0.25). There was no effect of age on
      reproducibility of recall. These data suggest that recall of diet from the very
      distant past, during a distinct time period such as high school, is reasonably
      reproducible. Although further studies of validity are needed, such information
      may be sufficiently precise to assess the influence of remote diet in
      epidemiologic studies.

PMID- 8580298
TI  - A population-based case-control study of the relationship between cigarette
      smoking and nasopharyngeal cancer (United States).
AB  - This case-control investigation, based on the Selected Cancers Study, assesses
      the association between cigarette smoking and nasopharyngeal cancer, a relatively
      rare neoplasm in the United States. Men who were diagnosed pathologically with
      nasopharyngeal cancer during 1984-88 were included as cases in the analysis if
      they were 15 to 39 years old in 1968, and lived in the areas covered by eight
      cancer registries in the US (n = 113). Control men were selected by random-digit
      telephone dialing (n = 1,910). Using logistic regression analysis with adjustment
      for potential confounding factors, it was found that relative to nonsmokers, the
      risks of nasopharyngeal cancer were 2.3 (95 percent confidence interval [CI] =
      1.3-4.0) and 1.4 (CI = 0.8-2.6) for former and current smokers, respectively.
      Using pack-years as a measure, adjusted odds ratio (OR) estimates were 1.3, 1.8,
      2.5, and 3.9 for smoking for less than 15, 15-29, 30-44, and 45 or more pack
      years, respectively. When squamous cell carcinoma was used as an outcome, the
      smoking/nasopharyngeal-cancer association became stronger. The analysis did not
      show interactions between smoking and alcohol consumption, or prior nasal
      diseases. The results of this study suggest that cigarette smoking may be related
      to the occurrence of nasopharyngeal cancer (especially squamous cell carcinoma)
      among US men.

PMID- 8580299
TI  - Reproductive risk factors for colorectal adenomatous polyps (New York City, NY,
      United States).
AB  - Events of reproductive life, such as parity and age at menarche, have been found
      in some but not all studies to be associated with risk for colorectal cancer in
      females. Because adenomatous polyps (adenomas) are precursors of colorectal
      cancer, we investigated whether reproductive variables were associated with
      colorectal adenomas. We conducted a case-control study among patients examined in
      three colonoscopy practices in New York City (NY, United States) from 1986 to
      1988. Adenoma cases (n = 128) were defined as women who had an adenoma detected
      at the index colonoscopy with no history of inflammatory bowel disease, adenomas,
      or cancer. Controls (n = 283) were women with a normal index colonoscopy and no
      history of inflammatory bowel disease, adenomas, or cancer. The adjusted odds
      ratio (OR) for the association of early menarche (age less than 13 years) with
      adenomas was 0.6 (95 percent confidence interval = 0.4-0.9). Parity, history of
      spontaneous or induced abortion, infertility, type of menopause, age at
      menopause, use of oral contraceptives, and use of menopausal hormone replacement
      therapy were not associated statistically significantly with adenoma risk,
      although some possible trends were observed. Our findings do not implicate
      reproductive events, nulliparity, or overexposure to estrogens or to menstrual
      cycles as mechanisms of increased risk for colorectal neoplasia.

PMID- 8580301
TI  - Cancer in Mediterranean migrants--based on studies in France and Australia.
AB  - Whether non-European Mediterranean populations also benefit from the protective
      effect on health of the so-called Mediterranean diet is not know yet, as national
      mortality statistics are available in neither North Africa nor the Near East.
      This article investigates the cancer profile of Maghrebian and Near Eastern
      migrants, by gathering and discussing data from recent studies on cancer
      mortality in Mediterranean migrants of various origins in France and Australia.
      In France, the migrants originating from Morocco, and in Australia, the migrants
      originating from the Near East, have a lower mortality from all cancers than
      their host countries and than Italian migrants. Concerning specific sites,
      Moroccan and Near Eastern migrants have a cancer profile which is quite similar
      to that of the Italian migrants, with relatively low risks compared with the
      local-born for certain cancers typical of affluent societies (colon and rectum,
      breast, ovary, and prostate). In addition, the non-European Mediterranean
      migrants are protected even more than the Italians in the same host country from
      esophagus cancer, and Moroccans in France have a much lower risk than the local
      born for lung cancer. Lastly, they tend to have a relatively high risk for some
      cancers which are likely to have a viral etiology: e.g., nasopharynx (Italians
      and Near Easterners), liver (Near Eastern males), and possibly cervix
      (Moroccans).

PMID- 8580300
TI  - Effect of twinship on incidence of cancer of the testis, breast, and other sites
      (Sweden).
AB  - It has been suggested that cancers of the testis and breast are associated with
      exposure to estrogens and other hormones in utero. Twin pregnancies have higher
      levels of pregnancy-associated hormones than singleton pregnancies, and these
      levels may be higher in dizygotic than in monozygotic twin pregnancies. Through a
      large population-based study of twins, we assessed the hypothesis that levels of
      pregnancy-associated hormones have etiologic importance for cancers of the
      testis, breast, and other sites. The incidence of all cancers among 46,767
      members of the Swedish Twin Registry was compared with the incidence among the
      Swedish general population. We found testicular cancer excess among dizygotic
      twins (observed/expected[O/E ratio = 2.3, CI = 1.1-4.2) compared with older men
      (O/E ratio = 1.2, CI = 0.5-2.4). In addition, a substantially elevated incidence
      of breast cancer was observed in dizygotic twin women aged 20 to 29 years (O/E =
      6.7, CI = 2.9-13.1). None of the other age or zygosity groups showed notable
      elevations in incidence of testicular, breast, or other cancers. We conclude that
      dizygotic twinship may be associated with cancer of the breast and testis among
      young adults. These findings support the concept that pregnancy hormones are
      associated with risk of testicular and breast cancer, although non-hormonal
      aspects of twin pregnancy that vary with respect to zygosity cannot be excluded
      as explanatory factors.

PMID- 8580302
TI  - Green-tea consumption and risk of stomach cancer: a population-based case-control
      study in Shanghai, China.
AB  - The effect of drinking Chinese green tea on the risk of stomach cancer was
      evaluated in a population-based case-control study conducted in Shanghai, China,
      from October 1991 to December 1993. Eligible cases were incident cases of primary
      stomach cancer diagnosed during the study period among residents of Hongkou
      district and Nanhui county aged under 80 years. Controls were selected from the
      same street or commune where the case resided and were matched to the cases on
      age (within three years) and gender. A total of 711 cases and 711 matched
      controls, more than 90 percent of the eligible subjects, completed the interview.
      Information was obtained on the types of tea used, age when habitual tea drinking
      started, frequency of new batches of tea leaves used per day, number of cups
      brewed from each batch, total duration of drinking for each batch, strength and
      temperature of the tea consumed. Statistical analysis was based on modelling
      through conditional logistic regression. After adjusting for age, gender, place
      of residence, education, birthplace, alcohol consumption, and cigarette smoking,
      the odds ratio (OR) comparing drinkers of green tea with nondrinkers was 0.71 (95
      percent confidence interval = 0.54-0.93). The adjusted OR decreased with
      increasing number of new batches of the green tea consumed each day (P value
      trend = 0.006). With the largest series of stomach cancer cases to date, this
      study found green-tea consumption associated with lower risk of stomach cancer.
      Among drinkers of green tea, the risk of stomach cancer did not depend on the age
      when habitual green-tea drinking started. Green tea may disrupt gastric
      carcinogenesis at both the intermediate and the late stages.

PMID- 8580303
TI  - Cancer mortality among sub-Saharan African migrants in France.
AB  - Not only are there few data on sub-Saharan migrant populations, but relatively
      little information is available on cancer patterns in Africa. This report
      presents cancer mortality patterns among the 290,000 sub-Saharan African migrants
      in France. Risks of mortality from different cancers in migrants born in West,
      Central, East, and 'Other' parts of Africa have been compared with that observed
      in the local-born population, using mortality data from the period 1979-85 and
      population data from the 1982 French census. Relative risks were adjusted for
      important confounding factors such as social class and area of residence.
      Compared with natives, overall mortality from cancer is lower in sub-Saharan
      African migrants. Higher cancer mortality risks, however, are observed among
      males for several sites: liver in Central and West Africans; bladder in West
      Africans; and non-Hodgkin's lymphoma in Other African migrants. For females,
      risks were elevated for nasopharyngeal cancers in Other African and liver in West
      African migrants. The results are, for the most part, consistent with the few
      available data on cancer patterns in Africa, and with the patterns observed in
      African migrants to England and Wales (UK).

PMID- 8580304
TI  - Olive oil, other dietary fats, and the risk of breast cancer (Italy).
AB  - Data from a multicenter case-control study on breast cancer conducted in Italy
      have been used to analyze the relationship of olive oil and other dietary fats to
      breast cancer risk. Cases were 2,564 women hospitalized with histologically
      confirmed, incident breast cancer. Controls were 2,588 women admitted to the same
      network of hospitals for acute, non-neoplastic, non-hormone related, non
      digestive tract disorders. Cases and controls were interviewed between 1991 and
      1994 using a validated food-frequency questionnaire. The data were modelled
      through multiple logistic regression controlling for demographic and reproductive
      breast-cancer risk factors, energy intake and, mutually, for types of dietary
      fat. For olive oil, compared with the lowest quintile, the odds ratios (OR) were
      1.05, 0.99, 0.93, and 0.87 for increasing quintiles of intake; in a model
      postulating linear logit increase, the OR per unit (30 g) was 0.89 (95 percent
      confidence interval [CI] = 0.81-0.99, P = 0.03). Among other oils or fats
      considered, the OR for the highest level of intake was 0.72 (CI = 0.6-0.9) for a
      group of specific seed oils (including safflower, maize, peanut, and soya)
      compared with nonusers. The ORs for the highest cf lowest level of intake were
      0.80 for mixed or unspecified seed oils, 0.95 for butter, and 0.96 for margarine.
      The study, based on a large dataset from various Italian regions, shows an
      inverse relationship of breast cancer risk with intake of olive oil and other
      vegetable oils, but not with butter or margarine.

PMID- 8580307
TI  - Trans-membrane peptide and protein structures in fluid membranes via NMR.

PMID- 8580305
TI  - Organochlorine compounds and estrogen-related cancers in women.
AB  - The organochlorines, a diverse group of some 15,000 compounds, have been
      implicated increasingly as being harmful to humans. Some congeners of DDT and PCB
      elicit very weak estrogenic responses in animals, while the dioxin TCDD and
      related compounds have antiestrogenic properties. This review summarizes the
      evidence regarding whether certain organochlorine compounds, usually as
      persistent food-chain contaminants, increase the risk of breast and endometrial
      cancers through their estrogenic potential. In humans, neither ecologic data nor
      occupational studies provide clear support for an association between
      organochlorine exposure and the occurrence of these cancers. In our summary
      analysis of occupational exposure, the rate ratio of breast cancer for exposed cf
      unexposed women was 0.84 (95 percent confidence interval [CI] = 0.50-1.33) for
      PCBs and 1.08 (CI = 0.68-1.58) for TCDD. Similarly, effect estimates close to
      unity were found in summary analysis of breast cancer case-control studies
      regarding levels of DDE and PCB in adipose tissue or serum. In two recent nested
      case-control studies using stored specimens, the odds ratio per standard
      deviation increase in serum p,p'-DDE was 1.27 (CI = 0.95-1.69). Although
      estrogenic effects of certain organochlorine compounds should be easier to detect
      on the endometrium, we know of no analytic epidemiologic studies of endometrial
      cancer published to data. We conclude that available data do not indicate that
      organochlorines will affect the risk of these two cancers in any but the most
      unusual situation.

PMID- 8580306
TI  - Phytoestrogens, body composition, and breast cancer.
AB  - To the extent that diet is involved in the etiology of breast cancer, its effect
      may be mediated, in part, through hormonal mechanisms. It has been suggested that
      the consumption of phytoestrogens is related inversely to breast cancer risk.
      Phytoestrogens are weak estrogens of plant derivation that may have
      antiestrogenic effects through competitively binding to estrogen receptors, thus
      diminishing the binding of stronger endogenous estrogens. This paper advances the
      hypothesis that, through this mechanism, dietary phytoestrogens may attenuate the
      adverse consequences of obesity on the development of postmenopausal breast
      cancer. Such an association might partly explain the low breast cancer rates
      observed among postmenopausal Hispanic women despite their greater adiposity, an
      important breast cancer risk factor. This hypothesis would lead us to expect that
      obesity increases the risk of postmenopausal breast cancer in women consuming
      small quantities of phytoestrogens but does not increase risk in women consuming
      larger quantities. If the hypothesis is confirmed, such as association could have
      important implications for reducing breast cancer risk through diet, using
      naturally occurring substances, particularly in women for whom postmenopausal
      obesity is an important health concern.

PMID- 8580308
TI  - A novel theoretical approach to the analysis of dendritic transients.
AB  - A novel theoretical framework for analyzing dendritic transients is introduced.
      This approach, called the method of moments, is an extension of Rall's cable
      theory for dendrites. It provides analytic investigation of voltage attenuation,
      signal delay, and synchronization problems in passive dendritic trees. In this
      method, the various moments of a transient signal are used to characterize the
      properties of the transient. The strength of the signal is measured by the time
      integral of the signal, its characteristic time is determined by its centroid
      ("center of gravity"), and the width of the signal is determined by a measure
      similar to the standard deviation in probability theory. Using these signal
      properties, the method of moments provides theorems, expressions, and efficient
      algorithms for analyzing the voltage response in arbitrary passive trees. The
      method yields new insights into spatiotemporal integration, coincidence detection
      mechanisms, and the properties of local interactions between synaptic inputs in
      dendritic trees. The method can also be used for matching dendritic neuron models
      to experimental data and for the analysis of synaptic inputs recorded
      experimentally.

PMID- 8580309
TI  - A mu-conotoxin-insensitive Na+ channel mutant: possible localization of a binding
      site at the outer vestibule.
AB  - We describe a mutation in the outer vestibule region of the adult rat skeletal
      muscle voltage-gated Na+ channel (microliter) that dramatically alters binding of
      mu-conotoxin GIIIA (mu-CTX). Mutating the glutamate at position 758 to glutamine
      (E758Q) decreased mu-CTX binding affinity by 48-fold. Because the mutant channel
      showed both low tetrodotoxin (TTX) and mu-CTX affinities, these results suggested
      that mu-CTX bound to the outer vestibule and implied that the TTX- and mu-CTX
      binding sites partially overlapped in this region. The mutation decreased the
      association rate of the toxin with little effect on the dissociation rate,
      suggesting that Glu-758 could be involved in electrostatic guidance of mu-CTX to
      its binding site. We propose a mechanism for mu-CTX block of the Na+ channel
      based on the analogy with saxitoxin (STX) and TTX, on the requirement of mu-CTX
      to have an arginine in position 13 to occlude the channel, and on this
      experimental result suggesting that mu-CTX binds in the outer vestibule. In this
      model, the guanidinium group of Arg-13 of the toxin interacts with two carboxyls
      known to be important for selectivity (Asp-400 and Glu-755), with the association
      rate of the toxin increased by interaction with Glu-758 of the channel.

PMID- 8580310
TI  - A new method to study shape recovery of red blood cells using multiple optical
      trapping.
AB  - In this new method for studying the shape recovery of deformed red blood cells,
      three optical traps ("optical tweezers") induce a parachute-shaped red cell
      deformation, which is comparable to the deformation in small capillaries. The
      shape recovery is recorded, and a relaxation time is obtained for each individual
      red blood cell. The sensitivity of this technique for the detection of
      differences in relaxation times is demonstrated on subpopulations of density
      separated red blood cells: "young" cells have shorter (162 ms) and "old" cells
      have longer (353 ms) relaxation times compared with the total population (271
      ms). The relaxation time is remarkably shorter (114 ms) when the plasma
      surrounding the cells is replaced by a phosphate-buffered saline solution. The
      main advantages of this technique are the relatively short measuring and
      preparation time and the physiological type of deformation and shape recovery in
      which all relevant cell properties play a role. Therefore, especially when
      automated further, the technique may be a powerful tool for the study of
      (sub)populations of pathological red blood cells.

PMID- 8580311
TI  - Interpreting photoactivated fluorescence microscopy measurements of steady-state
      actin dynamics.
AB  - A continuum model describing the steady-state actin dynamics of the cytoskeleton
      of living cells has been developed to aid in the interpretation of photoactivated
      fluorescence experiments. In a simplified cell geometry, the model assumes
      uniform concentrations of cytosolic and cytoskeletal actin throughout the cell
      and no net growth of either pool. The spatiotemporal evolution of the fluorescent
      actin population is described by a system of two coupled linear partial
      differential equations. An analytical solution is found using a Fourier-Laplace
      transform and important limiting cases relevant to the design of experiments are
      discussed. The results demonstrate that, despite being a complex function of the
      parameters, the fluorescence decay in photoactivated fluorescence experiments has
      a biphasic behavior featuring a short-term decay controlled by monomer diffusion
      and a long-term decay governed by the monomer exchange rate between the
      polymerized and unpolymerized actin pools. This biphasic behavior suggests a
      convenient mechanism for extracting the parameters governing the fluorescence
      decay from data records. These parameters include the actin monomer diffusion
      coefficient, filament turnover rate, and ratio of polymerized to unpolymerized
      actin.

PMID- 8580313
TI  - Chemical oscillations arise solely from kinetic nonlinearity and hence can occur
      near equilibrium.
AB  - A minimal kinetic scheme for a system displaying sustained chemical oscillations
      is presented. The system is isothermal, and all steps in the scheme are
      kinetically reversible. The oscillations are analyzed and the crucial points
      elucidated. Both positive and negative feedback, if properly introduced, support
      oscillations, provided the state responsible for feedback is optimally buffered.
      It is shown that the requisite nonlinearity is introduced at the kinetic level
      because of feedback regulation and not, as is usually assumed, by large
      affinities that introduce nonlinearity at the thermodynamic level. Hence,
      sustained oscillations may occur near equilibrium.

PMID- 8580312
TI  - Local positive feedback by calcium in the propagation of intracellular calcium
      waves.
AB  - In many types of eukaryotic cells, the activation of surface receptors leads to
      the production of inositol 1,4,5-trisphosphate and calcium release from
      intracellular stores. Calcium release can occur in complex spatial patterns,
      including waves of release that traverse the cytoplasm. Fluorescence video
      microscopy was used to view calcium waves in single mouse neuroblastoma cells.
      The propagation of calcium waves was slowed by buffers that bind calcium quickly,
      such as BAPTA, but not by a buffer with slower on-rate, EGTA. This shows that a
      key feedback event in wave propagation is rapid diffusion of calcium occurring
      locally on a scale of < 1 micron. The length-speed product of wavefronts was used
      to determine that calcium acting in feedback diffuses at nearly the rate expected
      for free diffusion in aqueous solution. In cytoplasm, which contains immobile
      Ca2+ buffers, this rate of diffusion occurs only in the first 0.2 ms after
      release, within 0.4 micron of a Ca2+ release channel mouth. Calcium diffusion
      from an open channel to neighboring release sites is, therefore, a rate
      determining regenerative step in calcium wave propagation. The theoretical
      limitations of the wave front analysis are discussed.

PMID- 8580314
TI  - A model for nucleotide sequences.
AB  - We propose a model for generating "artificial" nucleotide sequences and, by the
      method of mapping those sequences onto a "DNA-walk," we analyze the presence of
      correlation between nucleotides. Artificial sequences are constructed
      considering, basically, interactions between first neighbors and between more
      distant units. We show that long-range correlations may be favored by the
      occurrence of intrastrand interactions, which give a nonlinear characteristic to
      the sequence.

PMID- 8580315
TI  - Ligand-receptor interaction rates in the presence of convective mass transport.
AB  - The rate of binding of a ligand to receptors on the cell surface can be diffusion
      limited. We analyze the kinetics of binding, diffusion-limited in a stationary
      liquid, in the presence of convective mass transport. We derive a formula that
      expresses the reaction kinetics in terms of the mass transfer coefficient. A
      moderately transport-limited kinetics is not readily recognizable from the shape
      of the binding curve and may lead to erroneous estimates of the rate
      coefficients. We apply our results to practically important cases: a cell
      suspension in a stirred volume of liquid and a confluent cell colony under a
      laminar stream. Using typical numbers characterizing the ligand-receptor
      interactions, we show that stirring and perfusion can be important factors
      determining the reaction rates. With the confluent colony, the early reaction
      kinetics requires a different treatment, and we provide it for the case of low
      receptor occupancy. We show that, even with a fast perfusion, a cell monolayer
      can transiently generate a zone of depletion of the ligand, and that would affect
      the early stages of the reaction. Our results are expressed in a simple
      analytical form and can be used for the design and interpretation of experimental
      data.

PMID- 8580316
TI  - Conformation and hydrogen ion titration of proteins: a continuum electrostatic
      model with conformational flexibility.
AB  - A new method for including local conformational flexibility in calculations of
      the hydrogen ion titration of proteins using macroscopic electrostatic models is
      presented. Intrinsic pKa values and electrostatic interactions between titrating
      sites are calculated from an ensemble of conformers in which the positions of
      titrating side chains are systematically varied. The method is applied to the
      Asp, Glu, and Tyr residues of hen lysozyme. The effects of different minimization
      and/or sampling protocols for both single-conformer and multi-conformer
      calculations are studied. For single-conformer calculations it is found that the
      results are sensitive to the choice of all-hydrogen versus polar-hydrogen-only
      atomic models and to the minimization protocol chosen. The best overall agreement
      of single-conformer calculations with experiment is obtained with an all-hydrogen
      model and either a two-step minimization process or minimization using a high
      dielectric constant. Multi-conformational calculations give significantly
      improved agreement with experiment, slightly smaller shifts between model
      compound pKa values and calculated intrinsic pKa values, and reduced sensitivity
      of the intrinsic pKa calculations to the initial details of the structure
      compared to single-conformer calculations. The extent of these improvements
      depends on the type of minimization used during the generation of conformers,
      with more extensive minimization giving greater improvements. The ordering of the
      titrations of the active-site residues, Glu-35 and Asp-52, is particularly
      sensitive to the minimization and sampling protocols used. The balance of strong
      site-site interactions in the active site suggests a need for including site-site
      conformational correlations.

PMID- 8580318
TI  - Predictability of EEG interictal spikes.
AB  - To determine whether EEG spikes are predictable, time series of EEG spike
      intervals were generated from subdural and depth electrode recordings from four
      patients. The intervals between EEG spikes were hand edited to ensure high
      accuracy and eliminate false positive and negative spikes. Spike rates (per
      minute) were generated from longer time series, but for these data hand editing
      was usually not feasible. Linear and nonlinear models were fit to both types of
      data. One patient had no linear or nonlinear predictability, two had
      predictability that could be well accounted for with a linear stochastic model,
      and one had a degree of nonlinear predictability for both interval and rate data
      that no linear model could adequately account for.

PMID- 8580317
TI  - Modeling the effect of glutamate diffusion and uptake on NMDA and non-NMDA
      receptor saturation.
AB  - One- and two-dimensional models of glutamate diffusion, uptake, and binding in
      the synaptic cleft were developed to determine if the release of single vesicles
      of glutamate would saturate NMDA and non-NMDA receptors. Ranges of parameter
      values were used in the simulations to determine the conditions when saturation
      could occur. Single vesicles of glutamate did not saturate NMDA receptors unless
      diffusion was very slow and the number of glutamate molecules in a vesicle was
      large. However, the release of eight vesicles at 400 Hz caused NMDA receptor
      saturation for all parameter values tested. Glutamate uptake was found to reduce
      NMDA receptor saturation, but the effect was smaller than that of changes in the
      diffusion coefficient or in the number of glutamate molecules in a vesicle. Non
      NMDA receptors were not saturated unless diffusion was very slow and the number
      of glutamate molecules in a vesicle was large. The release of eight vesicles at
      400 Hz caused significant non-NMDA receptor desensitization. The results suggest
      that NMDA and non-NMDA receptors are not saturated by single vesicles of
      glutamate under usual conditions, and that tetanic input, of the type typically
      used to induce long-term potentiation, will increase calcium influx by increasing
      receptor binding as well as by reducing voltage-dependent block of NMDA
      receptors.

PMID- 8580319
TI  - The mechanism of ion conduction by valinomycin: analysis of charge pulse
      responses.
AB  - Even though valinomycin has been employed and studied extensively for over 30
      years, the attempts to explain its mechanism have not been entirely successful.
      The basic carrier model uses four rate constants that describe association of an
      ion and carrier, transfer of the complex across the membrane, dissociation of the
      complex, and transfer of the free carrier back across the membrane. If the basic
      model is correct all of these constants are independent of ion concentration. In
      previous work with rubidium the rate constants for transfer of free carrier,
      transfer of complexes, and dissociation were independent of the concentration,
      but the rate constant for association varied markedly. No satisfactory
      explanation for these observations was proposed. In this study current
      relaxations after charge pulses have been analyzed using digital data
      acquisition, a Bayesian algorithm, and inspection of linear plots of residuals.
      In agreement with previous results the relaxations for sufficiently high rubidium
      or potassium concentrations contain three exponential components, but the rate
      constants for association and dissociation decrease to similar extents as ion
      concentration increases. A simple extension of the carrier model to allow a more
      realistic description of association and dissociation is in good agreement with
      the rate constants fitted in the present study but not those for low ion
      concentrations found in previous work. At high ion concentrations the rate
      limiting step in association appears to be a change in the conformation of the
      free carrier preceding the bimolecular association reaction. Transfer of neutral,
      free valinomycin between the surfaces is slower than the transfer of the charged
      ion-valinomycin complexes. Transfer of the complex may be hastened by deformation
      of the membrane, or transfer of the free carrier may be slowed by a need for
      conformation changes.

PMID- 8580320
TI  - Asymmetric modulation and blockade of the delayed rectifier in squid giant axons
      by divalent cations.
AB  - The effects of intracellular magnesium ions and extracellular calcium and
      magnesium ions on the delayed rectifier potassium ion channel, IK, were
      investigated from intracellularly perfused squid giant axons. Cao+2 and Mgo+2
      both blocked IK in a voltage-independent manner with a KD of approximately 100
      and 500 mM, respectively. This effect was obscured at potentials in the vicinity
      of the resting potential (approximately -60 mV) by a rightward shift of the
      steady-state IK inactivation curve along the voltage axis. The addition of either
      calcium or magnesium ions to the extracellular solution also produced the well
      known shift of the IK activation curve along the voltage axis. Cao+2 was
      approximately twice as effective in this regard as Mgo+2. The IK activation
      kinetics were slowed by Cao+2, but deactivation kinetics were not altered, as
      shown previously. Similar results were obtained with Mgo+2. The addition of
      magnesium ions to the intracellular perfusate shifted the activation curve along
      the voltage axis in the negative direction (without producing block) by
      approximately the same among as the Mgo+2 shift of this curve in the positive
      direction. Moreover, Mgi+2 substantially slowed the deactivation kinetics,
      whereas the effects of Mgi+2 on activation kinetics at strongly depolarized
      potentials were relatively minor. At modest depolarizations, Mgi+2 significantly
      reduced the delay before IK activation. These results are essentially the mirror
      image of the effects on gating of extracellular divalent cations.

PMID- 8580321
TI  - Description of modal gating of the cardiac calcium release channel in planar
      lipid membranes.
AB  - Single channel activity of the cardiac ryanodine-sensitive calcium-release
      channel in planar lipid membranes was studied in order to elucidate the calcium
      dependent mechanism of its steady-state behavior. The single channel kinetics,
      observed with Cs+ as the charge carrier at different activating (cis) Ca2+
      concentrations in the absence of ATP and Mg2+, were similar to earlier reports
      and were extended by analysis of channel modal behavior. The channel displayed
      three episodic levels of open probability defining three gating modes: H (high
      activity), L (low activity), and I (no activity). The large difference in open
      probabilities between the two active modes resulted from different bursting
      patterns and different proportions of two distinct channel open states. I-mode
      was without openings and can be regarded as the inactivated mode of the channel;
      L-mode was composed of short and sparse openings; and H-mode openings were longer
      and grouped into bursts. Modal gating may explain calcium-release channel
      adaptation (as transient prevalence of H-mode after Ca2+ binding) and the
      inhibitory effects of drugs (as stabilization of mode I), and it provides a basis
      for understanding the regulation of calcium release.

PMID- 8580322
TI  - Biochemical status of renal epithelial Na+ channels determines apparent channel
      conductance, ion selectivity, and amiloride sensitivity.
AB  - Purified bovine renal papillary Na+ channels, when reconstituted into planar
      lipid bilayers, reside in three conductance states: a 40-pS main state, and two
      subconductive states (12-13 pS and 24-26 pS). The activity of these channels is
      regulated by phosphorylation and by G-proteins. Protein kinase A (PKA)-induced
      phosphorylation increased channel activity by increasing the open state time
      constants from 160 +/- 30 (main conductance), and 15 +/- 5 ms (both lower
      conductances), respectively, to 365 +/- 30 ms for all of them. PKA
      phosphorylation also altered the closed time of the channel from 250 +/- 30 ms to
      200 +/- 35 ms, thus shifting the channel into a lower-conductance, long open time
      mode. PKA phosphorylation increased the PNa:PK of the channel from 7:1 to 20:1,
      and shifted the amiloride inhibition curve to the right (apparent K(i)amil from
      0.7 to 20 microM). Pertussis toxin-induced ADP-ribosylation of either
      phosphorylated of either phosphorylated or nonphosphorylated channels decreased
      the PNa:PK to 2:1 and 4:1, respectively, and altered K(i)amil to 8 and 2 microM
      for phosphorylated and nonphosphorylated channels, respectively. GTP-gamma-S
      treatment of either phosphorylated or nonphosphorylated channels resulted in an
      increase of PNa:PK to 30:1 and 10:1, respectively, and produced a leftward shift
      in the amiloride dose-response curve, altering K(i)amil to 0.5 and 0.1 microM,
      respectively. These results suggest that amiloride-sensitive renal Na+ channel
      biophysical characteristics are not static, but depend upon the biochemical state
      of the channel protein and/or its associated G-protein.

PMID- 8580324
TI  - Fluorine-19 NMR studies of glucosyl fluoride transport in human erythrocytes.
AB  - Fluorine-19 magnetization transfer studies have been used to measure the
      transport rate of glucopyranosyl fluorides under equilibrium exchange conditions.
      Although rate constants and permeabilities could be determined for beta-D
      glucopyranosyl fluoride, the exchange rate for alpha-D-glucopyranosyl fluoride
      was found to be too slow for determination using this method. The time-dependent
      decomposition of the beta-glucopyranosyl fluoride also limits the accuracy of the
      numerical results for this species; however, it is clear that the permeabilities
      of the alpha and beta forms differ significantly, i.e., P beta > P alpha. This
      observation is in contrast to recent observations for n-fluoro-n-deoxyglucose,
      for which P alpha > P beta for n = 2, 3, 4, or 6. The difference can be explained
      in terms of a simple alternating conformation model in which one of the
      conformations (with an external sugar-binding site) exhibits a preference for the
      beta form of the molecule, while the second conformation (with an internal sugar
      binding site) exhibits a preference for the alpha form. Fluorine/hydroxyl
      substitutions unmask these preferences by selectively reducing the binding to one
      of the conformations, depending on the specific site of fluorination.

PMID- 8580323
TI  - Glutamate substitution in repeat IV alters divalent and monovalent cation
      permeation in the heart Ca2+ channel.
AB  - In voltage-gated ion channels, residues responsible for ion selectivity were
      identified in the pore-lining SS1-SS2 segments. Negatively charged glutamate
      residues (E393, E736, E1145, and E1446) found in each of the four repeats of the
      alpha 1C subunit were identified as the major determinant of selectivity in Ca2+
      channels. Neutralization of glutamate residues by glutamine in repeat I (E393Q),
      repeat III (E1145Q), and repeat IV (E1446Q) decreased the channel affinity for
      calcium ions 10-fold from the wild-type channel. In contrast, neutralization of
      glutamate residues in repeat II failed to significantly alter Ca2+ affinity.
      Likewise, mutation of neighboring residues in E1149K and D1450N did not affect
      the channel affinity, further supporting the unique role of glutamate residues
      E1145 in repeat III and E1446 in repeat IV in determining Ca2+ selectivity.
      Conservative mutations E1145D and E1446D preserved high-affinity Ca2+ binding,
      which suggests that the interaction between Ca2+ and the pore ligand sites is
      predominantly electrostatic and involves charge neutralization. Mutational
      analysis of E1446 showed additionally that polar residues could achieve higher
      Ca2+ affinity than small hydrophobic residues could. The role of high-affinity
      calcium binding sites in channel permeation was investigated at the single
      channel level. Neutralization of glutamate residue in repeats I, II, and III did
      not affect single-channel properties measured with 115 mM BaCl2. However,
      mutation of the high-affinity binding site E1446 was found to significantly
      affect the single-channel conductance for Ba2+ and Li+, providing strong evidence
      that E1446 is located in the narrow region of the channel outer mouth. Side-chain
      substitutions at 1446 in repeat IV were used to probe the nature of divalent
      cation-ligand interaction and monovalent cation-ligand interaction in the calcium
      channel pore. Monovalent permeation was found to be inversely proportional to the
      volume of the side chain at position 1446, with small neutral residues such as
      alanine and glycine producing higher Li+ currents than the wild-type channel.
      This suggests that steric hindrance is a major determinant for monovalent cation
      conductance. Divalent permeation was more complex. Ba2+ single-channel
      conductance decreased when small neutral residues such as glycine were replaced
      by bulkier ones such as glutamine. However, negatively charged amino acids
      produced single-channel conductance higher than predicted from the size of their
      side chain. Hence, negatively charged residues at position 1446 in repeat IV are
      required for divalent cation permeation.

PMID- 8580325
TI  - Viral and cellular small integral membrane proteins can modify ion channels
      endogenous to Xenopus oocytes.
AB  - A slowly activated, inward current could be evoked from Xenopus oocytes in
      response to application of a strong (approximately -190 mV) hyperpolarizing
      pulse. However, a much lesser hyperpolarization (approximately -130 mV) was able
      to evoke a similar current from oocytes that expressed the cellular proteins IsK
      and phospholemman, the synthetic protein SYN-C, and the NB protein of influenza B
      virus. All of these currents were carried principally by Cl-, and they had
      similar blocker profiles. The time course (the function of time that described
      the current increase during a hyperpolarizing voltage-clamp pulse, i.e.,
      activation kinetics) varied from one batch of oocytes to another, but did not
      vary within each batch with the type of protein expressed. This slowly activated,
      inward current evoked by hyperpolarization to approximately -130 mV required the
      expression of a characteristic, minimum level of each of the proteins IsK, SYN-C,
      and NB. However, not every integral membrane protein expressed in oocytes allowed
      substantial inward currents to be generated at -130 mV. Oocytes that expressed
      large amounts of the M2 protein of influenza A virus, which is known to possess
      an intrinsic cation channel activity, did not display a Cl- current when
      hyperpolarized to -130 mV. These results suggest that expression of any of the
      four proteins-IsK, phospholemman, SYN-C, or NB- acts as an activator of an
      endogenous Cl- conductance.

PMID- 8580326
TI  - A quantitative description of the E-4031-sensitive repolarization current in
      rabbit ventricular myocytes.
AB  - We have measured the E-4031-sensitive repolarization current (IKr) in single
      ventricular myocytes isolated from rabbit hearts. The primary goal of this
      analysis was a description of the IKr kinetic and ion transfer properties.
      Surprisingly, the maximum time constant of this component was 0.8 s at 33-34
      degrees C, which is significantly greater than the value of 0.18 s previously
      reported under similar conditions in the original measurements of IKr from guinea
      pig ventricular myocytes. The primary, novel feature of our analysis concerns the
      relationship of the bell-shaped curve that describes the voltage dependence of
      the kinetics and the sigmoidal curve that describes the activation of IKr. The
      midpoint of the latter occurred at approximately +10 mV on the voltage axis, as
      compared to -30 mV for the point on the voltage axis at which the maximum time
      constant occurred. Moreover, the voltage dependence of the kinetics was much
      broader than the steepness of the activation curve would predict. Taken together,
      these results comprise a gating current paradox that is not resolved by the
      incorporation of a fast inactivated state in the analysis. The fully activated
      current-voltage relation for IKr exhibited strong inward-going rectification, so
      much so that the current was essentially nil at +30 mV, even though the channel
      opens rapidly in this voltage range. This result is consistent with the lack of
      effect of E-4031 on the early part of the plateau phase of the action potential.
      Surprisingly, the reversal potential Of /Kr was ~15 mV positive to the potassium
      ion equilibrium potential,which indicates that this channel carries inward
      current during the latter part of the repolarization phase of the action
      potential.

PMID- 8580327
TI  - Trypsin and forskolin decrease the sensitivity of L-type calcium current to
      inhibition by cytoplasmic free calcium in guinea pig heart muscle cells.
AB  - A key feature of trypsin action on ionic membrane currents including L-type Ca2+
      current (ICa) is the removal of inactivation upon intracellular application. Here
      we report that trypsin also occludes the resting cytoplasmic free Ca2+ ([Ca2+]i)
      induced inhibition of peak ICa in isolated guinea pig ventricular cardiomyocytes,
      using the whole-cell patch clamp in combination with the Fura-2 ratio
      fluorescence technique. The effectiveness of trypsin to guard ICa against [Ca2+]i
      induced inhibition was compared with that of forskolin, as cAMP-dependent
      phosphorylation had been suggested to confer protection against [Ca2+]i-induced
      inactivation. Intracellular dialysis of trypsin (1 mg/ml) augmented ICa by 7.2
      fold, significantly larger than the threefold increase induced by forskolin (3
      microM). Forskolin application after trypsin dialysis did not further enhance
      ICa. An increase in [Ca2+]i from resting levels (varied by 0.2, 10, and 40 mM
      EGTA dialysis) to submicromolar concentrations after replacement of external Na+
      (Na(o)+) with tetraethylammonium (TEA+) resulted in monotonic inhibition of
      control ICa, elicited from a holding potential of -40 mV at 22 degrees C. AFter
      trypsin dialysis, however, ICa became less sensitive to submicromolar [Ca2+]i;
      the [Ca2+]i of half-maximal inhibition (K0.5, normally around 60 nM) increased by
      approximately 20-fold. Forskolin also increased the K0.5 by approximately
      threefold. These and accompanying kinetic data on ICa decay are compatible with a
      model in which it is assumed that Ca2+ channels can exist in two modes (a high
      open probability "willing" and a low open probability "reluctant" mode) that are
      in equilibrium with one another. An increase in [Ca2+]i places a larger fraction
      of channels in the reluctant mode. This interconversion is hindered by cAMP
      dependent phosphorylation and becomes nearly impossible after tryptic digestion.

PMID- 8580328
TI  - Trypsin increases availability and open probability of cardiac L-type Ca2+
      channels without affecting inactivation induced by Ca2+.
AB  - The patch-clamp technique was employed to investigate the response of single L
      type Ca2+ channels to the protease trypsin applied to the intracellular face of
      excised membrane patches from guinea pig ventricular myocytes. Calpastatin and
      ATP were used to prevent run-down of Ca2+ channel activity monitored with 96 mM
      Ba2+ as charge carrier in the presence of 2.5 microM (-)-BAYK 8644. Upon
      application of trypsin (100 micrograms/ml) channel activity was enhanced fourfold
      and remained elevated upon removal of trypsin, as expected of a proteolytic,
      irreversible modification. The trypsin effect was not mediated by a proteolytic
      activation of protein kinases, as evidenced by the insensitivity of this effect
      to protein kinase inhibitors. Trypsin-modified Ca2+ channels exhibited the usual
      run-down phanomenon upon removal of calpastatin and ATP. In ensemble average
      currents trypsin-induced changes of channel function are apparent as a threefold
      increase in peak current and a reduction in current inactivation. At the single
      channel level these effects were based on about a twofold increase in both Ca2+
      channels' availability and open probability. Neither the actual number of
      channels in the patch nor their unitary conductance as well as reversal potential
      was changed by trypsin. The Ca(2+)-induced inactivation was not impaired, as
      judged by a comparable sensitivity of trypsin-modified Ca2+ channels to
      intracellular Ca2+. Similarly, trypsin treatment did not affect the sensitivity
      of Ca2+ channels to phenylalkylmine inhibition. The observed alterations in
      channel function are discussed in terms of possible structural correlates.

PMID- 8580329
TI  - Interaction of picrotoxin with GABAA receptor channel-lining residues probed in
      cysteine mutants.
AB  - We used the substituted-cysteine-accessibility method to identify the channel
      lining residues in a region (257-261) near the putative cytoplasmic end of the M2
      membrane-spanning segment of the rat gamma-aminobutyric acid type A (GABAA)
      receptor alpha 1 subunit. The residues alpha 1Val257 and alpha 1Thr261 were
      accessible to charged, sulfhydryl-specific reagents applied extracellularly in
      both the open and closed states. The accessibility of alpha 1V257C and alpha
      1T261C in the closed state implies that the gate must be at least as close to the
      cytoplasmic end of the channel as alpha 1Val257. Also, the positively charged
      reagent methanethiosulfonate ethylammonium penetrated from the extracellular end
      of the channel to alpha 1T261C, with which it reacted, indicating that the anion
      selectivity filter is closer to the cytoplasmic end of the channel than this
      residue is. Co-application of picrotoxin prevented the sulfhydryl reagents from
      reacting with alpha 1V257C but did not prevent reaction with the more
      extracellular residue alpha 1T261C. Picrotoxin protection of alpha 1V257C may be
      due to steric block by picrotoxin bound in the channel at the level of alpha
      1Val257; however, if this protection is allosteric, it is not due to the
      induction of the resting closed state in which alpha 1V257C was accessible to
      sulfhydryl reagent.

PMID- 8580330
TI  - Concentration-jump analysis of voltage-dependent conductances activated by
      glutamate and kainate in neurons of the avian cochlear nucleus.
AB  - We have examined the mechanisms underlying the voltage sensitivity of alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionate receptors in voltage-clamped outside-out
      patches and whole cells taken from the nucleus magnocellularis of the chick.
      Responses to either glutamate or kainate had outwardly rectifying current-voltage
      relations. The rate and extent of desensitization during prolonged exposure to
      agonist, and the rate of deactivation after brief exposure to agonist, decreased
      at positive potentials, suggesting that a kinetic transition was sensitive to
      membrane potential. Voltage dependence of the peak conductance and of the
      deactivation kinetics persisted when desensitization was reduced with aniracetam
      or blocked with cyclothiazide. Furthermore, the rate of recovery from
      desensitization to glutamate was not voltage dependent. Upon reduction of
      extracellular divalent cation concentration, kainate-evoked currents increased
      but preserved rectifying current-voltage relations. Rectification was strongest
      at lower kainate concentrations. Surprisingly, nonstationary variance analysis of
      desensitizing responses to glutamate or of the current deactivation after kainate
      removal revealed an increase in the mean single-channel conductance with more
      positive membrane potentials. These data indicate that the rectification of the
      peak response to a high agonist concentration reflects an increase in channel
      conductance, whereas rectification of steady-state current is dominated by
      voltage-sensitive channel kinetics.

PMID- 8580331
TI  - In vitro study of phase resetting and phase locking in a time-comparison circuit
      in the electric fish, Eigenmannia.
AB  - The electric fish Eigenmannia generates on oscillating weak electric field. The
      amplitude and timing information of this electric field is perceived by
      electroreceptors distributed on its skin. The pathway of timing information,
      consisting of spherical cells and giant cells, was studied in an in vitro
      preparation. The giant cells were identified to be endogenous oscillators and
      thus have the functional advantage of phase locking more easily to a periodic
      stimulus with a frequency in the range of the intrinsic frequency. Their
      spontaneous rhythmic activity was perturbed by delivering excitatory single
      pulses or periodic pulses via their synaptic inputs. The regular and irregular
      dynamics produced by periodic stimulation were discussed in the context of a
      mathematical analysis of the response to single pulses. Ambiguous representations
      of the timing of the stimulus pulse were observed and could be related to this
      analysis. Some spontaneously firing cells could be silenced with periodic
      excitatory stimulation in a narrow frequency and amplitude range. Some
      irregularly firing cells continued to fire periodically for several seconds after
      phase locking to a periodic stimulus. This study is the first description of an
      endogenous oscillator in a system devoted to the precise timing of sensory
      events.

PMID- 8580332
TI  - Small angle x-ray scattering studies of magnetically oriented lipid bilayers.
AB  - Magnetically oriented lipid/detergent bilayers are potentially useful for studies
      of membrane-associated molecules and complexes using x-ray scattering and nuclear
      magnetic resonance (NMR). To establish whether the system is a reasonable model
      of a phospholipid bilayer, we have studied the system using x-ray solution
      scattering to determine the bilayer thickness, interparticle spacing, and
      orientational parameters for magnetically oriented lipid bilayers. The
      magnetically orientable samples contain the phospholipid L-alpha
      dilauroylphosphatidylcholine (DLPC) and the bile salt analog 3-[(3
      cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate (CHAPSO) in a 3:1
      molar ratio in 70% water (w/v) and are similar to magnetically orientable samples
      used as NMR media for structural studies of membrane-associated molecules. A
      bilayer thickness of 30 A was determined for the DLPC/CHAPSO particles, which is
      the same as the bilayer thickness of pure DLPC vesicles, suggesting that the
      CHAPSO is not greatly perturbing the lipid bilayer. These data, as well as NMR
      data on molecules incorporated in the oriented lipid particles, are consistent
      with the sample consisting of reasonably homogeneous and well dispersed lipid
      particles. Finally, the orientational energy of the sample suggests that the size
      of the cooperatively orienting unit in the samples is 2 x 10(7) phospholipid
      molecules.

PMID- 8580333
TI  - Effects of pH and cholesterol on DMPA membranes: a solid state 2H- and 31P-NMR
      study.
AB  - The effect of pH and cholesterol on the dimyristoylphosphatidic acid (DMPA) model
      membrane system has been investigated by solid state 2H- and 31P-NMR. It has been
      shown that each of the three protonation states of the DMPA molecule corresponds
      to a 31P-NMR powder pattern with characteristic delta sigma values; this implies
      additionally that the proton exchange on the membrane surface is slow on the NMR
      time scale (millisecond range). Under these conditions, the 2H-labeled lipid
      chains sense only one magnetic environment, indicating that the three spectra
      detected by 31P-NMR are related to charge-dependent local dynamics or
      orientations of the phosphate headgroup or both. Chain ordering in the fluid
      phase is also found to depend weakly on the charge at the interface. In addition,
      it has also been found that the first pK of the DMPA membrane is modified by
      changes in the lipid lateral packing (gel or fluid phases or in the presence of
      cholesterol) in contrast to the second pK. The incorporation of 30 mol%
      cholesterol affects the phosphatidic acid bilayer in a way similar to what has
      been reported for phosphatidylcholine/cholesterol membranes, but to an extent
      comparable to 10-20 mol % sterol in phosphatidylcholines. However, the
      orientation and molecular order parameter of cholesterol in DMPA are similar to
      those found in dimyristoylphosphatidylcholine.

PMID- 8580334
TI  - X-ray diffraction and calorimetric study of N-lignoceryl sphingomyelin membranes.
AB  - Differential scanning calorimetry and x-ray diffraction have been used to
      investigate hydrated multibilayers of N-lignoceryl sphingomyelin (C24:0-SM) in
      the hydration range 0-75 wt % H2O. Anhydrous C24:0-SM exhibits a single
      endothermic transition at 81.3 degrees C (delta H = 3.6 kcal/mol). At low
      hydration (12.1 wt % H2O), three different endothermic transitions are observed:
      low-temperature transition (T1) at 39.4 degrees C (transition enthalpy (delta H1)
      = 2.8 kcal/mol), intermediate-temperature transition (T2) at 45.5 degrees C, and
      high-temperature transition (T3) at 51.3 degrees C (combined transition enthalpy
      (delta H2 + 3) = 5.03 kcal/mol). On increasing hydration, all three transition
      temperatures of C24:0-SM decrease slightly to reach limiting values of 36.7
      degrees C (T1), 44.4 degrees C (T2), and 48.4 degrees C (T3) at approximately 20
      wt % H2O. At 22 degrees C (below T1), x-ray diffraction of C24:0-SM at different
      hydration levels shows two wide-angle reflections, a sharp one at 1/4.2 A-1 and a
      more diffuse one at 1/4.0 A-1 together with lamellar reflections corresponding to
      bilayer periodicities increasing from d = 65.4 A to a limiting value of 71.1 A.
      Electron density profiles show a constant bilayer thickness dp-p approximately 50
      A. In contrast, at 40 degrees C (between T1 and T2) a single sharp wide-angle
      reflection at approximately 1/4.2 A-1 is observed. The lamellar reflections
      correspond to a larger bilayer periodicity (increasing from d = 69.3-80.2 A) and
      there is some increase in dp-p (52-56 A) with hydration. These structural
      parameters,together with calculated lipid thickness and molecular area
      considerations, suggest that the low temperature endotherm(T1) of hydrated C24:0
      SM corresponds to a transition from a tilted, gel state (Gel I) with partially
      interdigitated chains to an untilted, or less tilted, gel state (Gel 11). At 600C
      (above T3), the usual liquid-crystalline La bilayer structure (d = 59.5-66.3A; dp
      p -46 A) is present at all hydrations. Comparison with the behavior of C18:0-SM
      indicates that the in equivalence of length of the sphingosine (C18) and
      lignoceryl (C24) chains results in a more complex gel phase polymorphism for the
      sphingosine (C18) and lignoceryl (C24) chains results in a more complex gel phase
      polymorphism for C24:0-SM.

PMID- 8580336
TI  - High-speed magic angle spinning solid-state 1H nuclear magnetic resonance study
      of the conformation of gramicidin A in lipid bilayers.
AB  - One- and two-dimensional solid-state 1H nuclear magnetic resonance spectra of
      gramicidin A incorporated in a dimyristoylphosphatidylcholine membrane have been
      obtained with use of high-speed magic angle spinning. By rotating the sample at
      13 kHz, it is possible to observe signals in the 1H spectra between 6.0 and 9.0
      ppm attributable to the aromatic protons of the tryptophan residues and the
      formyl group proton of gramicidin A. Two-dimensional solid-state COSY spectra
      provided information for the peak assignments. Moreover, changes in the 1H
      spectra have been observed as a function of the co-solubilization solvent
      initially used to prepare the samples and therefore as a function of the
      conformation adopted by gramicidin A. Three organic solvents have been used:
      trifluoroethanol, a mixture of methanol/chloroform (1:1 v/v), and ethanol. The
      conformational interconversion of gramicidin A from the double helix conformation
      to the channel structure for the sample prepared from ethanol was confirmed by
      following the time evolution of the proton spectra.

PMID- 8580335
TI  - High resolution 1H nuclear magnetic resonance of a transmembrane peptide.
AB  - Although the strong 1H-1H dipolar interaction is known to result in severe
      homogeneous broadening of the 1H nuclear magnetic resonance (NMR) spectra of
      ordered systems, in the fluid phase of biological and model membranes the rapid,
      axially symmetric reorientation of the molecules about the local bilayer normal
      projects the dipolar interaction onto the motional symmetry axis. Because the
      linewidth then scales as (3 cos2 theta-1)/2, where theta is the angle between the
      local bilayer normal and the magnetic field, the dipolar broadening has been
      reduced to an "inhomogeneous" broadening by the rapid axial reorientation. It is
      then possible to obtain high resolution 1H-NMR spectra of membrane components by
      using magic angle spinning (MAS). Although the rapid axial reorientation
      effectively eliminates the homogeneous dipolar broadening, including that due to
      n = 0 rotational resonances, the linewidths observed in both lipids and peptides
      are dominated by low frequency motions. For small peptides the most likely slow
      motions are either a "wobble" or reorientation of the molecular diffusion axis
      relative to the local bilayer normal, or the reorientation of the local bilayer
      normal itself through surface undulations or lateral diffusion over the curved
      surface. These motions render the peptide 1H-NMR lines too broad to be observed
      at low spinning speeds. However, the linewidths due to these slow motions are
      very sensitive to spinning rate, so that at higher speeds the lines become
      readily visible. The synthetic amphiphilic peptide K2GL20K2A-amide (peptide-20)
      has been incorporated into bilayers of 1,2-di-d 27-myristoyl-sn-glycero-3
      phosphocholine (DMPC-d54) and studied by high speed 1H-MAS-NMR. The linewidths
      observed for this transbilayer peptide, although too broad to be observable at
      spinning rates below -5 kHz, are reduced to 68 Hz at a spinning speed of 14 kHz
      (at 500C). Further improvements in spinning speed and modifications in sample
      composition designed to reduce the effectiveness of the slow motions responsible
      for the linewidth should result in significant further reduction in peptide
      linewidths. With this technique, there is now the potential for the use of 1H-MAS
      NMR for the study of conformation, folding, and dynamics of small membrane
      peptides and protein fragments.

PMID- 8580337
TI  - Study of phospholipid structure by 1H, 13C, and 31P dipolar couplings from two
      dimensional NMR.
AB  - Various motionally averaged 31P-1H, 13C-1H, 1H-1H, and 31P-13C dipolar couplings
      were measured for natural-abundance and unoriented phosphocholine in the L alpha
      phase. The couplings were obtained and assigned by a variety of advanced and
      partly novel two-dimensional solid-state NMR experiments. Whereas 31P-1H and 31P
      13C dipolar couplings provide long-range structural constraints, geminal 1H-1H
      couplings and the signs of 13C-1H couplings are important new elements in a
      segmental order-tensor analysis of the lipid headgroup and glycerol backbone. The
      implications of these measured dipolar couplings for the conformational exchange
      of the lipid headgroup and the bending of the headgroup from the glycerol
      backbone are discussed. These dipolar couplings are also analyzed
      semiquantitatively in terms of the segmental order tensor.

PMID- 8580338
TI  - Polymorphism, mesomorphism, and metastability of monoelaidin in excess water.
AB  - The polymorphic and metastable phase behavior of monoelaidin dry and in excess
      water was studied by using high-sensitivity differential scanning calorimetry and
      time-resolved x-ray diffraction in the temperature range of 4 degrees C to 60
      degrees C. To overcome problems associated with a pronounced thermal history
      dependent phase behavior, simultaneous calorimetry and time-resolved x-ray
      diffraction measurements were performed on individual samples. Monoelaidin/water
      samples were prepared at room temperature and stored at 4 degrees C for up to 1
      week before measurement. The initial heating scan from 4 degrees C to 60 degrees
      C showed complex phase behavior with the sample in the lamellar crystalline (Lc0)
      and cubic (Im3m, Q229) phases at low and high temperatures, respectively. The Lc0
      phase transforms to the lamellar liquid crystalline (L alpha) phase at 38 degrees
      C. At 45 degrees C, multiple unresolved lines appeared that coexisted with those
      from the L alpha phase in the low-angle region of the diffraction pattern that
      have been assigned previously to the so-called X phase (Caffrey, 1987, 1989).
      With further heating the X phase converts to the Im3m cubic phase. Regardless of
      previous thermal history, cooling calorimetric scans revealed a single exotherm
      at 22 degrees C, which was assigned to an L alpha+cubic (Im3m, Q229)-to-lamellar
      gel (L beta) phase transition. The response of the sample to a cooling followed
      by a reheating or isothermal protocol depended on the length of time the sample
      was incubated at 4 degrees C. A model is proposed that reconciles the complex
      polymorphic, mesomorphic, and metastability interrelationships observed with this
      lipid/water system. Dry monoelaidin exists in the lamellar crystalline (beta)
      phase in the 4 degrees C to 45 degrees C range. The beta phase transforms to a
      second lamellar crystalline polymorph identified as beta* at 45 degrees C that
      subsequently melts at 57 degrees C. The beta phase observed with dry monoelaidin
      is identical to the LcO phase formed by monoelaidin that was dispersed in excess
      water and that had not been previously heated.

PMID- 8580339
TI  - Leakage of membrane vesicle contents: determination of mechanism using
      fluorescence requenching.
AB  - Agents such as antimicrobial peptides and toxins can permeabilize membrane
      vesicles to cause leakage of entrapped contents in either a graded or an all-or
      none fashion. Determination of which mode of leakage is induced is an important
      step in understanding the molecular mechanism of membrane permeabilization.
      Wimley et al. (1994, Protein Sci. 3:1362-1378) have developed a fluorescence
      method for distinguishing the two modes that makes use of the dye/quencher pair 8
      aminonapthalene-1,3,6 trisulfonic acid (ANTS)/p-xylene-bis-pyridinium bromide
      (DPX) without the usual need for the physical separation of vesicles from
      released contents. Their "requenching" method establishes the mode of release
      through the fluorescence changes that occur when DPX is added externally to a
      solution of vesicles that have released some fraction of their contents. However,
      the requenching method as originally stated ignored the possibility of
      preferential release of dye or quencher. Here we extend the theory of the method
      to take into account preferential release and the effects of graded leakage. The
      ratio of the rates of release of the cationic quencher DPX and anionic dye 8
      aminonapthalene-1,3,6 trisulfonic acid can be estimated by means of the theory.
      For graded leakage, we show that the release of the markers does not coincide
      with the fluorescence changes observed in the standard leakage assay. This is
      true for self-quenching dyes as well and means that 1) the amount of released
      material will be overestimated and 2) the kinetics will be nonexponential and
      have artificially high apparent rates. We show how the extended requenching
      analysis allows the results of leakage experiments to be corrected for artifacts
      that result from graded and preferential leakage. Experimental evidence is
      presented for the existence of peptide-induced preferential graded leakage of DPX
      from both neutral and anionic vesicles.

PMID- 8580340
TI  - Electric field-induced concentration gradients in planar supported bilayers.
AB  - A simple method of generating electric field-induced concentration gradients in
      planar supported bilayers has been developed. Gradients of charged, fluorescently
      labeled probes were visualized by epifluorescence microscopy and could be
      observed at field strengths as low as 1 V/cm. Steady-state concentration
      gradients can be described by a simple competition between random diffusion and
      electric field-induced drift. A model based on this principle has been used to
      determine the diffusion coefficient of the fluorescent probes. This technique
      achieves a degree of electrical manipulation of supported bilayers that offers a
      variety of possibilities for the development of new molecular architectures and
      the study of biological membranes.

PMID- 8580341
TI  - Bilayer nanotubes and helical ribbons formed by hydrated galactosylceramides:
      acyl chain and headgroup effects.
AB  - The molecular basis of bilayer tubule formation in hydrated galactosylceramide
      (GalCer) dispersions has been investigated by synthesizing different chain-pure
      GalCers and examining their aqueous mesomorphic phase structure by freeze
      fracture and negative-stain electron microscopy. Thermotropic characterization of
      the GalCer species by differential scanning calorimetry provided supplementary
      information that verified the phase state under which morphological observations
      were carried out. Under aqueous conditions and at room temperature, N-24:1 delta
      15(cis) GalSph, the predominant monounsaturated, nonhydroxy acyl species of
      bovine brain GalCer (NFA-GalCer), formed cylindrical mesomorphic self-assemblies
      consisting almost exclusively of "nanotubes," i.e., lipid bilayer tubules of
      relatively uniform length and diameter (length, 250-400 nm; diameter, 25-30 nm).
      In contrast, N-24:0 GalSph, the major saturated, nonhydroxy acyl species of
      bovine brain GalCer, displayed no tendency to form these relatively small
      "nanotubes." Rather, N-24:0 GalSph formed larger, variable-length ribbon-like
      structures (length, 5,000-10,000 nm) that often appeared to undulate and,
      occasionally, appeared to be helically twisted. Interestingly, bovine brain
      GalCer, which contains high levels of the N-24:1 delta 15(cis) and N-24:0 species
      as well as 2-hydroxy acyl chains, formed multilamellar liposomes of variable size
      and showed little tendency to form cylindrical structures. This result suggested
      that changes to the polar interface/headgroup region imparted by the 2-hydroxy
      acyl species strongly influenced bilayer tubule and cylinder formation in GalCer.
      To define this influence more clearly, other sphingoid-based and glycerol-based
      lipids were investigated. Morphological characterization of N-24:1 delta 15(cis)
      sphingosylphosphorylcholine (24:1 SM) revealed no evidence of bilayer cylinder or
      tubule formation. Similar results were obtained with aqueous dispersions of 1
      palmitoyl-2-nervonoyl phosphatidylcholine (16:0, 24:1 PC). Hence, the bulkier,
      more hydrated, zwitterionic phosphocholine headgroup inhibited the formation of
      bilayer nanotubes and cylinders under physiological saline conditions.

PMID- 8580342
TI  - IR spectroscopic determination of gel state miscibility in long-chain
      phosphatidylcholine mixtures.
AB  - We report on the gel-state microaggregation in binary mixtures of
      diacylphosphatidylcholines over temperatures ranging from -19 degrees C to near
      the gel-to-liquid crystal transition. Microaggregates with lateral dimensions in
      the range 1-100 chains were detected and measured with an isotope infrared method
      that relates the splitting or the shape of the methylene scissors band to
      aggregate size. Measurements were made on fully hydrated dispersions of
      diC18DPC/diC20HPC, diC18DPC/diC22HPC, and diC18DPC/diC24HPC at molar ratios of
      4:1. Low levels of aggregation were determined with reference to the spectrum of
      the random mixture diC18DPC/diC18HPC. For diC18DPC/diC20HPC at -19 degrees C,
      which previous calorimetric measurements have indicated is a nearly ideal, we
      found about 4% of the minority component chains to be involved in aggregates. For
      diC18DPC/diC22HPC, the value increased to about 11%. DiC18DPC/diC24HPC was found
      to be highly fractionated, in agreement with the earlier studies. The unit
      subcell, which defines the type of acyl-chain packing, was determined for the
      components of the mixtures. The temperature behavior of the phases and the
      temperatures at which the minority component domains undergo dissolution were
      determined.

PMID- 8580343
TI  - Stopped-flow fluorometric study of the interaction of melittin with phospholipid
      bilayers: importance of the physical state of the bilayer and the acyl chain
      length.
AB  - Stopped-flow fluorometry has been employed to study the effects of melittin, the
      major protein component of bee venom, on dimyristoylphosphatidylcholine (DMPC)
      and dipalmitoylphosphatidylcholine (DPPC) small unilamellar vesicles (SUVs) on
      the millisecond time scale, before melittin-induced vesicle fusion takes place.
      Use is made of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH),
      which is an oriented fluorescent probe that anchors itself to the bilayer-water
      interface and is aligned parallel to the normal to the bilayer surface; its
      fluorescence anisotropy reports on the "fluidity" of the bilayer. For DMPC
      bilayers, melittin is found to decrease their fluidity only at their melting
      transition temperature. This perturbation appears to be exerted almost
      instantaneously on the millisecond time scale of the measurements, as deduced
      from the fact that its rate is comparable to that obtained by following the
      change in the fluorescence of the single tryptophan residue of melittin upon
      inserting itself into the bilayer. The perturbation is felt in the bilayer over a
      distance of at least 50 A, with measurements of transfer of electronic energy
      indicating that the protein is not sequestered in the neighborhood of TMA-DPH.
      The length of the acyl chains is found to be an important physical parameter in
      the melittin-membrane interaction: unlike the case of DMPC SUVs, melittin does
      not alter the fluidity of DPPC SUVs and has a considerably greater affinity for
      them. These results are discussed in terms of the concept of elastic distortion
      of the lipids, which results from a mismatch between the protein and the acyl
      chains that are attempting to accommodate it. Melittin is also found to cause a
      small (approximately 10%) enhancement in the total fluorescence intensity of TMA
      DPH, which is interpreted as indicating a reduction in the degree of hydration of
      the bilayer.

PMID- 8580344
TI  - Single cytoplasmic dynein molecule movements: characterization and comparison
      with kinesin.
AB  - Cytoplasmic dynein is a major microtubule motor for minus-end directed movements
      including retrograde axonal transport. To better understand the mechanism by
      which cytoplasmic dynein converts ATP energy into motility, we have analyzed the
      nanometer-level displacements of latex beads coated with low numbers of
      cytoplasmic dynein molecules. Cytoplasmic dynein-coated beads exhibited greater
      lateral movements among microtubule protofilaments (ave. 5.1 times/microns of
      displacement) compared with kinesin (ave. 0.9 times/micron). In addition, dynein
      moved rearward up to 100 nm over several hundred milliseconds, often in
      correlation with off-axis movements from one protofilament to another. We suggest
      that single molecules of cytoplasmic dynein move the beads because 1) there is a
      linear dependence of bead motility on dynein/bead ratio, 2) the binding of beads
      to microtubules studied by laser tweezers is best fit by a first-order Poisson,
      and 3) the run length histogram of dynein beads follows a first-order decay. At
      the cellular level, the greater disorder of cytoplasmic dynein movements may
      facilitate transport by decreasing the duration of collisions between kinesin and
      cytoplasmic dynein-powered vesicles.

PMID- 8580345
TI  - Conformational changes in subdomain 2 of G-actin: fluorescence probing by dansyl
      ethylenediamine attached to Gln-41.
AB  - Gln-41 on G-actin was specifically labeled with a fluorescent probe, dansyl
      ethylenediamine (DED), via transglutaminase reaction to explore the
      conformational changes in subdomain 2 of actin. Replacement of Ca2+ with Mg2+ and
      ATP with ADP on G-actin produced large changes in the emission properties of DED.
      These substitutions resulted in blue shifts in the wavelength of maximum emission
      and increases in DED fluorescence. Excitation of labeled actin at 295 nm revealed
      energy transfer from tryptophans to DED. Structure considerations and Cu2+
      quenching experiments suggested that Trp-79 and/or Trp-86 serves as energy donors
      to DED. Energy transfer from these residues to DED on Gln-41 increased with the
      replacement of Ca2+ with Mg2+ and ATP with ADP. Polymerization of Mg-G-actin with
      MgCl2 resulted in much smaller changes in DED fluorescence than divalent cation
      substitution. This suggests that the conformation of loop 38-52 on actin is
      primed for the polymerization reaction by the substitution of Ca2+ with Mg2+ on G
      actin.

PMID- 8580346
TI  - Conformational transitions of alternating purine-pyrimidine DNAs in perchlorate
      ethanol solutions.
AB  - Conformational transitions of poly(dA-dC).poly(dG-dT), poly(dA-dT).poly(dA-dT),
      and other alternating purine-pyrimidine DNAs were studied in aqueous ethanol
      solutions containing molar concentrations of sodium perchlorate, which is a novel
      solvent stabilizing non-B duplexes of DNA. Using CD and UV absorption
      spectroscopies, we show that this solvent unstacks bases and unwinds the B-forms
      of the DNAs to transform them into the A-form or Z-form. In the absence of
      divalent cations poly(dA-dC).poly(dG-dT) can adopt both of these conformations.
      Its transition into the Z-form is induced at higher salt and lower ethanol
      concentrations, and at higher temperatures than the transition into the A-form.
      Submillimolar concentrations of NiCl2 induce a highly cooperative and slow A-Z
      transition or Z-Z' transition, which is fast and displays low cooperativity.
      Poly(dA-dT).poly(dA-dT) easily isomerizes into the A-form in perchlorate-ethanol
      solutions, whereas high perchlorate concentrations denature the polynucleotide,
      which then cannot adopt the Z-form. At low temperatures, however, NiCl2 also
      cooperatively induces the Z'-form in poly(dA-dT).poly(dA-dT). Poly(dI-dC).poly(dI
      dC) is known to adopt an unusual B-form in low-salt aqueous solution, which is
      transformed into a standard B-form by the combination of perchlorate and ethanol.
      NiCl2 then transforms poly(dI-dC).poly(dI-dC) into the Z'-form, which is also
      adopted by poly(dI-br5dC).poly(dI-br5dC).

PMID- 8580347
TI  - Excited state dynamics in photosystem I: effects of detergent and excitation
      wavelength.
AB  - Femtosecond transient absorption spectroscopy has been used to investigate the
      energy transfer and trapping processes in both intact membranes and purified
      detergent-isolated particles from a photosystem II deletion mutant of the
      cyanobacterium Synechocystis sp. PCC 6803, which contains only the photosystem I
      reaction center. Processes with similar lifetimes and spectra are observed in
      both the membrane fragments and the detergent-isolated particles, suggesting
      little disruption of the core antenna resulting from the detergent treatment. For
      the detergent-isolated particles, three different excitation wavelengths were
      used to excite different distributions of pigments in the spectrally
      heterogeneous core antenna. Only two lifetimes of 2.7-4.3 ps and 24-28 ps, and a
      nondecaying component are required to describe all the data. The 24-28 ps
      component is associated with trapping. The trapping process gives rise to a
      nondecaying spectrum that is due to oxidation of the primary electron donor. The
      lifetimes and spectra associated with trapping and radical pair formation are
      independent of excitation wavelength, suggesting that trapping proceeds from an
      equilibrated excited state. The 2.7-4.3 ps component characterizes the evolution
      from the initially excited distribution of pigments to the equilibrated excited
      state distribution. The spectrum associated with the 2.7-4.3 ps component is
      therefore strongly excitation wavelength dependent. Comparison of the difference
      spectra associated with the spectrally equilibrated state and the radical pair
      state suggests that the pigments in the photosystem I core antenna display some
      degree of excitonic coupling.

PMID- 8580348
TI  - The Ca2+ binding to deionized monomerized and to retinal removed
      bacteriorhodopsin.
AB  - In our continuing effort to characterize the metal cation binding in
      bacteriorhodopsin (bR) using Ca(2+)-specific electrodes, potentiometric titration
      was carried out on deionized solubilized bR (containing monomeric units) and
      deionized bacterioopsin (bR with its retinal removed). Scatchard plots were
      analyzed. The monomer was found to have plots similar to those of the trimer,
      suggesting that the binding sites in bR are localized within the protein monomer
      unit and not between the molecules within the trimer structure. This also
      supports the previous assumption that the curvature in the Scatchard plot of
      regenerated bR is not due to cooperativity of metal cation within the trimer, but
      rather due to multiple sites. Recent studies further support the finding that the
      curved Scatchard plot is not due to the cooperativity between the metal ions in
      the two high affinity sites, wherever they are. The results of the analysis of
      the Scatchard plot for deionized bacterioopsin have shown a change in the binding
      characteristics of the high affinity but not the low affinity sites from that
      observed in bR. This result supports previous conclusions that metal cations in
      the high affinity sites are not far from the retinal cavity.

PMID- 8580349
TI  - Charge displacement in bacteriorhodopsin during the forward and reverse bR-K
      phototransition.
AB  - Dried oriented purple membrane samples of Halobacterium salinarium were excited
      by 150 fs laser pulses of 620 nm with a 7 kHz repetition rate. An unusual complex
      picosecond electric response signal consisting of a positive and a negative peak
      was detected by a sampling oscilloscope. The ratio of the two peaks was changed
      by 1) reducing the repetition rate, 2) varying the intensity of the excitation
      beam, and 3) applying background illumination by light of 647 nm or 511 nm. All
      of these features can be explained by the simultaneous excitation of the
      bacteriorhodopsin ground form and the K intermediate. The latter was populated by
      the (quasi)continuous excitation attributable to its prolonged lifetime in a
      dehydrated state. Least-square analysis resulted in a 5 ps upper and 2.5 ps lower
      limit for the time constant of the charge displacement process, corresponding to
      the forward reaction. That is in good agreement with the formation time of K. The
      charge separation driven by the reverse phototransition was faster, having a time
      constant of a 3.5 ps upper limit. The difference in the rates indicates the
      existence of different routes for the forward and the reverse photoreactions.

PMID- 8580350
TI  - Photovoltage kinetics of the acid-blue and acid-purple forms of
      bacteriorhodopsin: evidence for no net charge transfer.
AB  - Time-resolved photovoltage measurements were performed with the acid-blue
      (bR605A) and acid-purple (bR565A) forms of bacteriorhodopsin (bR) in the time
      range from 25 ns to 100 s. The bR605A and bR565A pigments were formed by
      titration with H2SO4 in the absence and presence of 150 mM KCI, respectively.
      Qualitatively the kinetics of the charge displacement in these two states are
      similar and consist of two fast phases in one direction (100 ns bandwidth limited
      and approximately 1 microsecond) followed by a decay in the opposite direction
      via one component for bR605A (4.4 +/- 0.6 ms) or two components for bR565A (33 +/
      8 microseconds and 3.6 +/- 0.5 ms). The transient photovoltage signal returns
      exactly to the initial value after several milliseconds, well before the passive
      discharge of the electrical measuring system at 2 s. We conclude that no net
      charge transfer occurs in either bR605A or bR565A. The direction of the fast
      components is opposite that of net proton translocation in bR at pH 7. So, if the
      charge that moves back and forth is due to a proton, it moves first in the
      direction of the cytoplasmic side of the membrane (< 1 microsecond) and returns
      to its initial position via the 4.4 ms (bR605A) or the 33 microseconds and 3.6 ms
      (bR565A) decay components. The amplitude of the charge motion in both low pH
      forms is too large to be due to isomerization alone and is comparable to one of
      the major components in bR at pH 7.2

PMID- 8580351
TI  - Intramolecular charge transfer in the bacteriorhodopsin mutants Asp85-->Asn and
      Asp212-->Asn: effects of pH and anions.
AB  - The photovoltage kinetics of the bacteriorhodopsin mutants Asp212-->Asn and Asp85
      ->Asn after excitation at 580 nm have been investigated in the pH range from 0 to
      11. With the mutant Asp85-->Asn (D85N) at pH 7 no net charge translocation is
      observed and the signal is the same, both in the presence of Cl- (150 mM) and in
      its absence (75 mM SO4(2-)). Under both conditions the color of the pigment is
      blue (lambda max = 615 nm). The time course of the photovoltage kinetics is
      similar to that of the acid-blue form of wild-type, except that an additional
      transient charge motion occurs with time constants of 60 microseconds and 1.3 ms,
      indicating the transient deprotonation and reprotonation of an unknown group to
      and from the extracellular side of the membrane. It is suggested that this is the
      group XH, which is responsible for proton release in wild-type. At pH 1, the
      photovoltage signal of D85N changes upon the addition of Cl- from that
      characteristic for the acid-blue state of wild-type to that characteristic for
      the acid-purple state. Therefore, the protonation of the group at position at 85
      is necessary, but not sufficient for the chloride-binding. At pH 11, well above
      the pKa of the Schiff base, there is a mixture of "M-like" and "N-like" states.
      Net proton transport in the same direction as in wild-type is restored in D85N
      from this N-like state. With the mutant Asp212-->Asn (D212N), time-resolved
      photovoltage measurements show that in the absence of halide ions the signal is
      similar to that of the acid-blue form of wild-type and that no net charge
      translocation occurs in the entire pH range from 0 to 11. Upon addition of Cl- in
      the pH range from 3.8 to 7.2 the color of the pigment returns to purple and the
      photovoltage experiments indicate that net proton pumping is restored. However,
      this Cl(-)-induced activation of net charge-transport in D212N is only partial.
      Outside this pH range, no net charge transport is observed even in the presence
      of chloride, and the photovoltage shows the same chloride-dependent features as
      those accompanying the acid-blue to acid-purple transition of the wild-type.

PMID- 8580352
TI  - The protein conformation and a zinc-binding domain of an autoantigen from mouse
      seminal vesicle.
AB  - The protein conformation of a mouse seminal vesicle autoantigen was studied by
      circular dichroism spectroscopy. At pH 7.4, the spectrum in the UV region appears
      as one negative band at 217 nm and one positive band at 200 nm. This together
      with the predicted secondary structures indicates no helices but a mixture of
      beta form, beta turn, and unordered form in the protein molecule. The
      conformation is stable even at pH 10.5 or 3.0. The spectrum in the near-UV region
      consists of fine structures that are disturbed in acidic or alkaline solution.
      The environments around Trp2 and Trp82 of this protein were studied by intrinsic
      fluorescence and solute quenching. They give an emission peak at 345 nm, and
      about 87% of them are accessible to quenching by acrylamide. Correlating the
      quenching effect of CsCl and Kl on the protein fluorescence to the charged groups
      along the polypeptide chain suggests the difference in the "local charge" around
      the two tryptophan residues. The presence of ZnCl2 in the protein solution
      effects no change in the circular dichroism but perturbs the fluorescence due to
      Trp82. Analysis of the fluorescence data suggests a Zn(2+)-binding site on the
      protein, which cannot coordinate with both Ca2+ and Mg2+. The association
      constant for the complex formation is 1.35 x 10(5) +/- 0.04 x 10(5) M-1 at pH
      7.4.

PMID- 8580353
TI  - Kinetic analysis of dynamic 13C NMR spectra: metabolic flux, regulation, and
      compartmentation in hearts.
AB  - Control of oxidative metabolism was studied using 13C NMR spectroscopy to detect
      rate-limiting steps in 13C labeling of glutamate. 13C NMR spectra were acquired
      every 1 or 2 min from isolated rabbit hearts perfused with either 2.5 mM [2
      13C]acetate or 2.5 mM [2-13C]butyrate with or without KCl arrest. Tricarboxylic
      acid cycle flux (VTCA) and the exchange rate between alpha-ketoglutarate and
      glutamate (F1) were determined by least-square fitting of a kinetic model to NMR
      data. Rates were compared to measured kinetics of the cardiac glutamate
      oxaloacetate transaminase (GOT). Despite similar oxygen use, hearts oxidizing
      butyrate instead of acetate showed delayed incorporation of 13C label into
      glutamate and lower VTCA, because of the influence of beta-oxidation: butyrate =
      7.1 +/- 0.2 mumol/min/g dry wt; acetate = 10.1 +/- 0.2; butyrate + KCl = 1.8 +/-
      0.1; acetate + KCl = 3.1 +/- 0.1 (mean +/- SD). F1 ranged from a low of 4.4 +/-
      1.0 mumol/min/g (butyrate + KCl) to 9.3 +/- 0.6 (acetate), at least 20-fold
      slower than GOT flux, and proved to be rate limiting for isotope turnover in the
      glutamate pool. Therefore, dynamic 13C NMR observations were sensitive not only
      to TCA cycle flux but also to the interconversion between TCA cycle intermediates
      and glutamate.

PMID- 8580355
TI  - New fluorescent calcium indicators designed for cytosolic retention or measuring
      calcium near membranes.
AB  - A new family of fluorescent calcium indicators has been developed based on a new
      analog of BAPTA called FF6. This new BAPTA analog serves as a versatile synthetic
      intermediate for developing Ca2+ indicators targeted to specific intracellular
      environments. Two of these new Ca2+ indicators, fura-PE3 and fura-FFP18, are
      described in this report. Fura-PE3 is a zwitterionic indicator that resists the
      rapid leakage and compartmentalization seen with fura-2 and other polycarboxylate
      calcium indicators. In contrast to results obtained with fura-2, cells loaded
      with PE3 remain brightly loaded and responsive to changes in concentration of
      cytosolic free calcium for hours. Fura-FFP18 is an amphipathic indicator that to
      binds to liposomes and to cell membranes. Studies to be detailed later indicate
      that FFP18 functions as a near-membrane Ca2+ indicator and that calcium levels
      near the plasma membrane rise faster and higher than in the cytosol.

PMID- 8580354
TI  - Functional significance of a protein conformation change at the cytoplasmic end
      of helix F during the bacteriorhodopsin photocycle.
AB  - The second half of the photocycle of the light-driven proton pump
      bacteriorhodopsin includes proton transfers between D96 and the retinal Schiff
      base (the M to N reaction) and between the cytoplasmic surface and D96 (decay of
      the N intermediate). The inhibitory effects of decreased water activity and
      increased hydrostatic pressure have suggested that a conformational change
      resulting in greater hydration of the cytoplasmic region is required for proton
      transfer from D96 to the Schiff base, and have raised the possibility that the
      reversal of this process might be required for the subsequent reprotonation of
      D96 from the cytoplasmic surface. Tilt of the cytoplasmic end of helix F has been
      suggested by electron diffraction of the M intermediate. Introduction of bulky
      groups, such as various maleimide labels, to engineered cysteines at the
      cytoplasmic ends of helices A, B, C, E, and G produce only minor perturbation of
      the decays of M and N, but major changes in these reactions when the label is
      linked to helix F. In these samples the reprotonation of the Schiff base is
      accelerated and the reprotonation of D96 is strongly retarded. Cross-linking with
      benzophenone introduced at this location, but not at the others, causes the
      opposite change: the reprotonation of the Schiff base is greatly slowed while the
      reprotonation of D96 is accelerated. We conclude that, consistent with the
      structure from diffraction, the proton transfers in the second half of the
      photocycle are facilitated by motion of the cytoplasmic end of helix F, first
      away from the center of the protein and then back.

PMID- 8580356
TI  - The relationship between ligand-binding thermodynamics and protein-ligand
      interaction forces measured by atomic force microscopy.
AB  - The interaction forces between biotin and a set of streptavidin site-directed
      mutants with altered biotin-binding equilibrium and activation thermodynamics
      have been measured by atomic force microscopy. The AFM technique readily
      discriminates differences in interaction force between the site-directed (Trp to
      Phe or Ala) mutants. The interaction force is poorly correlated with both the
      equilibrium free energy of biotin binding and the activation free energy barrier
      to dissociation of the biotin-streptavidin complex. The interaction force is
      generally well correlated with the equilibrium biotin-binding enthalpy as well as
      the enthalpic activation barrier, but in the one mutant where these two
      parameters are altered in opposite directions, the interaction force is clearly
      correlated with the activation enthalpy of dissociation. These results suggest
      that the AFM force measurements directly probe the enthalpic activation barrier
      to ligand dissociation.

PMID- 8580357
TI  - Selectin- and integrin-mediated T-lymphocyte rolling and arrest on TNF-alpha
      activated endothelium: augmentation by erythrocytes.
AB  - The adhesive and hemodynamic forces that lead to lymphocyte rolling and arrest on
      activated endothelium and the biophysical role of various adhesion molecules and
      blood elements in this process are poorly understood. By quantifying their
      behaviour both in vivo and in vitro, we show here that erythrocytes facilitate
      selectin- and integrin-mediated rolling and binding of T-lymphocytes on tumor
      necrosis factor alpha-activated endothelium. The relative contribution of
      selectins and integrins to this process can be distinguished by using a simple
      mathematical expression of lymphocyte capture within the range of physiological
      shear stress. The need for selectin participation in lymphocyte capture increases
      with shear stress (> 1 dyn/cm2), and both beta 1 and beta 2 integrins act in
      synergy to produce adhesive drag on captured cells. These findings are
      potentially useful in developing strategies for intervening with T-cells in a
      variety of normal and pathological responses as well as for the delivery of
      genetically modified T-cells to their targets in vivo.

PMID- 8580359
TI  - Simultaneous measurement of bacterial flagellar rotation rate and swimming speed.
AB  - Swimming speeds and flagellar rotation rates of individual free-swimming Vibrio
      alginolyticus cells were measured simultaneously by laser dark-field microscopy
      at 25, 30, and 35 degrees C. A roughly linear relation between swimming speed and
      flagellar rotation rate was observed. The ratio of swimming speed to flagellar
      rotation rate was 0.113 microns, which indicated that a cell progressed by 7% of
      pitch of flagellar helix during one flagellar rotation. At each temperature,
      however, swimming speed had a tendency to saturate at high flagellar rotation
      rate. That is, the cell with a faster-rotating flagellum did not always swim
      faster. To analyze the bacterial motion, we proposed a model in which the torque
      characteristics of the flagellar motor were considered. The model could be
      analytically solved, and it qualitatively explained the experimental results. The
      discrepancy between the experimental and the calculated ratios of swimming speed
      to flagellar rotation rate was about 20%. The apparent saturation in swimming
      speed was considered to be caused by shorter flagella that rotated faster but
      produced less propelling force.

PMID- 8580358
TI  - On the roles of Ca2+ diffusion, Ca2+ buffers, and the endoplasmic reticulum in
      IP3-induced Ca2+ waves.
AB  - We have investigated the effects of Ca2+ diffusion, mobile and stationary Ca2+
      buffers in the cytosol, and Ca2+ handling by the endoplasmic reticulum on
      inositol 1,4,5-trisphosphate-induced Ca2+ wave propagation. Rapid equilibration
      of free and bound Ca2+ is used to describe Ca2+ sequestration by buffers in both
      the cytosol and endoplasmic reticulum (ER) lumen. Cytosolic Ca2+ regulation is
      based on a kinetic model of the inositol 1,4,5-trisphosphate (IP3) receptor of De
      Young and Keizer that includes activation and inhibition of the IP3 receptor Ca2+
      channel in the ER membrane and SERCA Ca2+ pumps in the ER. Diffusion of Ca2+ in
      the cytosol and the ER and the breakdown and diffusion of IP3 are also included
      in our calculations. Although Ca2+ diffusion is severely limited because of
      buffering, when conditions are chosen just below the threshold for Ca2+
      oscillations, a pulse of IP3 or Ca2+ results in a solitary trigger wave that
      requires diffusion of Ca2+ for its propagation. In the oscillatory regime
      repetitive wave trains are observed, but for this type of wave neither the wave
      shape nor the speed is strongly dependent on the diffusion of Ca2+. Local phase
      differences lead to waves that are predominately kinematic in nature, so that the
      wave speed (c) is related to the wavelength (lambda) and the period of the
      oscillations (tau) approximately by the formula c = lambda/tau. The period is
      determined by features that control the oscillations, including [IP3] and pump
      activity, which are related to recent experiments. Both solitary waves and wave
      trains are accompanied by a Ca2+ depletion wave in the ER lumen, similar to that
      observed in cortical preparations from sea urchin eggs. We explore the effect of
      endogenous and exogenous Ca2+ buffers on wave speed and wave shape, which can be
      explained in terms of three distinct effects of buffering, and show that
      exogenous buffers or Ca2+ dyes can have considerable influence on the amplitude
      and width of the waves.

PMID- 8580361
TI  - Teaching computer interfacing with virtual instruments in an object-oriented
      language.
AB  - LabVIEW is a graphic object-oriented computer language developed to facilitate
      hardware/software communication. LabVIEW is a complete computer language that can
      be used like Basic, FORTRAN, or C. In LabVIEW one creates virtual instruments
      that aesthetically look like real instruments but are controlled by sophisticated
      computer programs. There are several levels of data acquisition VIs that make it
      easy to control data flow, and many signal processing and analysis algorithms
      come with the software as premade VIs. In the classroom, the similarity between
      virtual and real instruments helps students understand how information is passed
      between the computer and attached instruments. The software may be used in the
      absence of hardware so that students can work at home as well as in the
      classroom. This article demonstrates how LabVIEW can be used to control data flow
      between computers and instruments, points out important features for signal
      processing and analysis, and shows how virtual instruments may be used in place
      of physical instrumentation. Applications of LabVIEW to the teaching laboratory
      are also discussed, and a plausible course outline is given.

PMID- 8580360
TI  - Diffusion coefficient of the cyclic GMP analog 8-(fluoresceinyl)thioguanosine
      3',5' cyclic monophosphate in the salamander rod outer segment.
AB  - Cyclic GMP (cGMP) is the intracellular messenger mediating phototransduction in
      retinal rods, with its longitudinal diffusion in the rod outer segment (ROS)
      likely to be a factor in determining light sensitivity. From the kinetics of cGMP
      activated currents in the truncated ROS of the salamander (Ambystoma tigrinum),
      the cGMP diffusion coefficient was previously estimated to be approximately 60 x
      10(-8) cm2 s-1. On the other hand, fluorescence measurements in intact salamander
      ROS using 8-(fluoresceinyl)thioguanosine 3',5'-cyclic monophosphate (Fl-cGMP) led
      to a diffusion coefficient for this compound of 1 x 10(-8) cm2 s-1; after
      corrections for differences in size and in binding to cellular components between
      cGMP and Fl-cGMP, this gave an upper limit of 11 x 10(-8) cm2 s-1 for the cGMP
      diffusion coefficient. To properly compare the two sets of measurements, we have
      examined the diffusion of Fl-cGMP in the truncated ROS. From the kinetics of Fl
      cGMP-activated currents, we have obtained a diffusion coefficient of 3 x 10(-8)
      cm2 s-1 for this analog; the cGMP diffusion coefficient measured from the same
      truncated ROSs was approximately 80 x 10(-8) cm2 s-1. Thus, a factor of 27
      appears appropriate for correcting differences in size and intracellular binding
      between cGMP and Fl-cGMP. Application of this correction factor to the Fl-cGMP
      diffusion coefficient measurements by Olson and Pugh (1993) gives a cGMP
      diffusion coefficient of approximately 30 x 10(-8) cm2 s-1, in reasonable
      agreement with the value measured from the truncated ROS.

PMID- 8580362
TI  - Chemokine and chemokine receptor mRNA expression in human platelets.
AB  - In order to study the role of platelets in inflammation we constructed a cDNA
      library from human platelet mRNA. By polymerase chain reaction (PCR) analysis of
      the library we have shown that platelets express mRNAs for the following
      chemokines: connective tissue activating peptide-III (CTAP-III), epithelial
      derived neutrophil activating factor-78 (ENA-78), RANTES and monocyte chemotactic
      protein-3 (MCP-3). Platelets also express mRNAs for interleukin 8 receptor A (IL
      8RA) and a novel chemokine receptor K5.5. These results suggest that chemokines
      may not only play an important role in platelet activation but can also influence
      the nature of the leukocyte infiltrate to sites of inflammation and infection, by
      the production of multiple chemokines with overlapping specificities.

PMID- 8580363
TI  - Genomic organization of the type I and type II IL-1 receptors.
AB  - Genomic clones spanning the human type I and type II interleukin-1 receptor loci
      have been isolated. Approximately 75 kb of genomic DNA is required to encode the
      type I receptor, and approximately 38 kb to encode the type II receptor. In each
      case, the receptor coding region is contained in only about 20 kb of DNA, with
      most of the rest of each locus representing the distance between the two (type II
      receptor) or three (type I receptor) presumptive promoters which drive
      transcription. The virtually identical location of introns within the ligand
      binding portion of the coding regions reinforces the presumption that the two
      receptors derive from a common ancestor. Yeast artificial chromosomes (YACs) have
      been isolated which contain the two IL-1 receptors. One of the YACs also contains
      the T1/ST2 IL-1 receptor-related gene. The relative map position of these three
      genes has been determined.

PMID- 8580364
TI  - The LIF response element of the alpha 2 macroglobulin gene confers LIF-induced
      transcriptional activation in embryonal stem cells.
AB  - Leukaemia Inhibitory Factor (LIF), an interleukin 6 (IL-6)-type cytokine, is an
      essential growth factor for murine embryonal stem cells. The LIF-receptor was
      known in these cells, but the cell-internal part of the signal cascade and the
      transcription factors through which LIF controls its growth-promoting target
      genes in embryonal stem cells, had not been identified. This study shows that the
      type II IL-6-response element of the rat alpha 2 macroglobulin (alpha 2M) gene,
      which mediates IL-6- and LIF-responses in hepatic cells, also functioned as a LIF
      response element (LIF-RE) in ES1 embryonal stem cells and P19 embryonal carcinoma
      cells. It conferred transcriptional activation by LIF of transfected reporter
      constructs in these cells. A characteristic DNA-binding activity interacting with
      this LIF-RE was induced by treatment of these cells with LIF. The complex between
      this activity and the LIF-RE had identical electrophoretic mobility, sequence
      specificity and kinetics of induction as the complex with the corresponding LIF
      response factor (LIF-RF) from hepatic cells. The transcription factor STAT3 was
      part of this complex, as shown by its reactivity with anti-STAT3 antibodies.
      Withdrawal of LIF from ES1 cells caused the induction of differentiation and the
      disappearance of this DNA-binding activity. Simultaneously, the surface density
      of high-affinity LIF receptors was reduced approximately 10-fold.

PMID- 8580365
TI  - Cytokines oncostatin M and interleukin 1 regulate the expression of the IL-6
      receptor (gp80, gp130).
AB  - The steady-state mRNA levels of the interleukin 6 receptor (IL-6R, gp80) and its
      signal transducing molecule, gp130, were examined in the rat hepatoma cell line,
      H-35, stimulated by cytokines IL-6, IL-1, oncostatin M (OSM) and/or Dexamethasone
      (Dex). In contrast to our previous findings in vivo [Geisterfer et al., 1993,
      Cytokine, 5:1] in vitro Dex seemed to be the major stimulator of IL-6R mRNA
      expression, whereas IL-6 seemed to have little effect on the expression of its
      own receptor mRNA levels. However, the presence of other cytokines influenced the
      Dex mediated stimulation of IL-6R expression. OSM stimulated IL-6R mRNA levels.
      At 6 h, cells stimulated with OSM showed a 2.1-fold increase in IL-6R mRNA
      expression. This stimulation was additive with the Dex-mediated stimulation of IL
      6R mRNA levels. In contrast, IL-1 inhibited the Dex-mediated stimulation of IL-6R
      mRNA. At the same time, IL-1 stimulated the presence of a second smaller mRNA
      transcript. This mRNA species contained the extracellular domain but lacked both
      the transmembrane and cytoplasmic domains of the IL-6R, suggesting alternate
      splicing, possibly coding for a soluble form of gp80. Unlike the gp80 IL-6R
      molecule, the expression of the gp130 molecule normally expressed as two species
      of mRNA was not regulated to any major extent in vitro. IL-1 and OSM stimulated
      both mRNA bands (7.5 and 9.0 kb) approximately 2-fold, whereas IL-6 stimulated
      mainly the upper 9.0 kb mRNA band.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8580366
TI  - Interleukin 1 binding to its type I, but not type II receptor, modulates the in
      vivo acute phase response.
AB  - Neutralizing monoclonal antibodies against the murine interleukin 1 (IL-1) type I
      (mAb 35F5) and type II receptor (mAb 4E2) were used to passively immunize mice
      prior to exogenous murine IL-1 alpha administration or a sterile-turpentine
      induced abscess. When mice were passively immunized with 35F5, the anorexia,
      weight loss and increased plasma acute phase protein levels in response to
      exogenous IL-1 alpha administration or a turpentine abscess were significantly
      attenuated. In contrast, passive immunization with 4E2 had only variable effects
      on food intake, body weight and the hepatic acute phase response in mice
      administered IL-1 alpha. In mice following a turpentine abscess, type II receptor
      blockade (4E2) either had no effect, or in some cases, actually increased the
      plasma IL-6 and acute phase protein responses. We conclude that in response to a
      turpentine abscess, the anorexia, weight loss and the induction of several
      hepatic acute phase reactants result in part from IL-1 binding to its type I
      receptor. Binding of IL-1 to the type II IL-1 receptor does not appear to be
      involved in the induction of these host nonspecific responses to inflammation.

PMID- 8580367
TI  - Augmentation of TNF cytotoxicity by protein kinase C inhibitors: role of
      arachidonic acid and manganese superoxide dismutase.
AB  - The protein kinase C (PKC) inhibitors bisindolylmaleimide, calphostin C, H-7 and
      staurosporine were examined for their effect on tumour necrosis factor (TNF)
      cytotoxic activity. PKC inhibitors potentiated the cytotoxic activity of TNF in
      TNF-sensitive cell lines (CL8-1 melanoma and WEHI-164 fibrosarcoma), but had no
      effect on TNF cytolytic activity in TNF-resistant cells (BL6-8 melanoma and MCA
      102 fibrosarcoma). The mechanism(s) of PKC inhibitor-mediated potentiation of the
      cytotoxic activity of TNF was investigated by analysing the effect of PKC
      inhibitors on TNF-induced arachidonic acid release in TNF-sensitive and 
      resistant cells. TNF induced the release of arachidonic acid in TNF-sensitive
      cells but had no effect in TNF-resistant cells. The combination of PKC inhibitor
      and TNF potentiated the release of arachidonic acid from TNF-sensitive cells, but
      failed to induce arachidonic acid release in TNF-resistant cells. Kinetic
      analysis of TNF-induced arachidonic acid release in CL8-1 melanoma cells revealed
      that it was an early event which preceded TNF tumour lytic activity. TNF was
      further shown to induce manganese superoxide dismutase (MnSOD) production in TNF
      sensitive cells but failed to induce MnSOD activity in TNF-resistant BL6-8 and
      MCA 102 cells. MnSOD acts as a scaveneger of toxic superoxide radicals and its
      induction by TNF paralleled arachidonic acid release. Although the PKC-selective
      inhibitor bisindolylmaleimide potentiated TNF-induced release of arachidonic
      acid, it blocked TNF-mediated induction of MnSOD in CL8-1 melanoma and WEHI-164
      fibrosarcoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8580368
TI  - Angiotensin-converting-enzyme inhibitors suppress synthesis of tumour necrosis
      factor and interleukin 1 by human peripheral blood mononuclear cells.
AB  - Administration of angiotensin-converting-enzyme (ACE) inhibitors reduce vascular
      proliferation following endothelial injury as well as progression of renal
      disease in various animal models. These effects might be due to interference with
      cytokines such as interleukin 1 (IL-1) or tumour necrosis factor alpha (TNF)
      since they have been implicated in regulating the effects of vascular cell growth
      factors such as fibroblast- and platelet-derived growth factors. We investigated
      the in vitro synthesis of IL-1 and TNF from human peripheral blood mononuclear
      cells (PBMC) in the presence of various ACE-inhibitors. Captopril dose
      dependently suppressed the IL-1 beta-induced synthesis of TNF by 74% (P < 0.01)
      and the IL-1 beta-induced synthesis of IL-1 alpha by 60% (P < 0.01). Cytokine
      synthesis induced by lipopolysaccharide was less affected. At concentrations
      suppressing TNF and IL-1, captopril did not reduce the synthesis of complement C3
      in the same cells. Enalapril and cilazapril also suppressed cytokine-induced
      cytokine synthesis. Ramipril, lisinopril, perindopril and spirapril had no
      significant effect on TNF synthesis suggesting that the effect was not related
      specifically to the inhibition of ACE. Accumulation of mRNA for IL-1 and TNF were
      not affected by captopril, suggesting a posttranscriptional effect. We conclude
      that certain ACE-inhibitors suppress IL-1 and TNF synthesis at a
      posttranscriptional level and might therefore influence cytokine-mediated cell
      growth.

PMID- 8580369
TI  - Relative cytokine-stimulating activities of surface components of the oral
      periodontopathogenic bacterium Actinobacillus actinomycetemcomitans.
AB  - The purpose of this study was to determine whether bacterial surface components
      other than lipopolysaccharide (LPS) could stimulate pro-inflammatory cytokine
      synthesis by mesenchymal and myelomonocytic cells in vitro. LPS, lipid A
      associated proteins (LAP) and saline-extractable surface-associated material
      (SAM) were isolated from the periodontopathogenic bacterium Actinobacillus
      actinomycetemcomitans and added to cultures of human gingival fibroblasts (HGFs),
      human PBMCs and the human myelomonocytic MonoMac-6 cell line. Pro-inflammatory
      cytokine release into culture supernatants was determined by two-site ELISAs.
      Contrary to expectation, the highly purified LPS extracted from this bacterium
      was significantly less potent than the other surface extracts in stimulating
      release of IL-1 beta, IL-6 and TNF-alpha by all three cell types. The SAM was the
      most potent cytokine-stimulating agent showing equivalent activity to highly
      purified E. coli LPS in stimulating IL-6 release by PBMCs. LAP also had cytokine
      stimulating activity although it was generally significantly less potent than the
      SAM. Thus in the case of this organism, which is involved in the pathology of
      chronic inflammatory diseases the LPS does not appear to be the major cytokine
      stimulating component.

PMID- 8580371
TI  - The effects of dietary lipid manipulation on the production of murine T cell
      derived cytokines.
AB  - Lymphocytes play an important part in the development and progression of a number
      of autoimmune and inflammatory disorders, which are characterized by the presence
      of activated T cells and cytokines at the site of tissue injury and in the
      circulation. There has been considerable interest in using dietary
      polyunsaturated fatty acids (PUFA), particularly the n-3 PUFA found in fish oils,
      in the therapy of these conditions; such therapies aim, primarily, to suppress T
      lymphocyte activity. While several studies have investigated the effects of fatty
      acids on the production of monocyte- and macrophage-derived cytokines, few have
      investigated their effects on the production of T cell-derived cytokines. Each of
      these studies have been restricted to IL-2 and have produced results which are
      not entirely clear. Moreover, there have been no studies to investigate the
      effects of dietary lipids other than fish oils on IL-2 production or the effects
      of dietary lipids on lymphokines other than IL-2. To investigate the effects of
      dietary lipid manipulation on the production of IL-2, IL-4, IL-10 and IFN-gamma
      by lymphocytes, mice were fed for 8 weeks on a low fat (LF) diet or one of 4 high
      fat diets, which contained 20% (by weight) hydrogenated coconut oil (HCO), olive
      oil (OO), safflower oil (SO) or menhaden oil (MO). Culture medium of lymphocytes
      from mice fed the OO or SO diets contained significantly more IL-2 than that of
      lymphocytes from mice fed the LF or HCO diets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8580370
TI  - IL-6 secretion by human peritoneal mesothelial and ovarian cancer cells.
AB  - Malignant ascites of epithelial ovarian cancer patients contains high levels of
      interleukin 6 (IL-6). The present study was conducted to compare the secretion of
      IL-6 by seven different human ovarian cancer cell lines (OVCA) and cultured human
      peritoneal mesothelial cells (HPMC) and to examine the regulation of its
      production by other cytokines. IL-6 was detected in supernatant medium of all
      mesothelial cell cultures (8/8) and 6/7 ovarian cancer cell lines. Levels of IL-6
      secreted by HPMC (median 27,100 pg/1 x 10(5) cells; range 3870-168,200) were 590
      fold higher (P < 0.01) than those secreted by OVCA (median 46 pg/1 x 10(5) cells;
      range 0-16,450). Treatment with TNF-alpha or IL-1 beta (both 10 ng/ml) for both
      types of cells and both cytokines resulted in a significant (P < 0.05) elevation
      of IL-6 production. In OVCA IL-6 secretion was increased 7- and 39-fold and in
      HPMC 6- and 8-fold, respectively. Under TNF-alpha treatment IL-6-levels secreted
      by HPMC were 149-fold higher (P < 0.01) than those generated by OVCA. Similarly,
      IL-1 beta-induced IL-6 levels were 102-fold higher in HPMC (median 288,800 pg/1 x
      10(5) cells; range 93,125-552,800) than in OVCA. IFN-gamma (10 ng/ml) increased
      IL-6 generation in OVCA (6-fold) but not HPMC. The proliferation of both cell
      types however, was significantly (P < 0.05) inhibited by IFN-gamma. Our results
      suggest that peritoneal mesothelial cells may be a prominent source of IL-6 in
      ovarian cancer-related ascites.

PMID- 8580372
TI  - Cholesterol feeding modulates spatial expression of TGF-beta 1 and beta 2 in
      aortas of Watanabe rabbits.
AB  - Several cytokines have been identified as markers of early atherosclerotic
      disease during vascular injury and remodelling. Of particular importance,
      transforming growth factor-beta (TGF-beta 1) has been found to be crucial in
      promoting connective tissue deposition resulting in both intimal and medial
      hyperplasia. However, the expression of TGF-beta 1 and beta 2 during cholesterol
      feeding in the Watanabe rabbit, an established model of hypercholesterolemia, has
      not been evaluated. Accordingly, we examined the expression of TGF-beta 1 and
      beta 2 signal from aortic segments of 10 heterozygous Watanabe rabbits with the
      use of reverse transcription-polymerase chain reaction (RT-PCR) amplification
      during normal non-supplemental diet and during 0.5% supplemental cholesterol
      feeding for a period of two months. TGF-beta transcripts from the aortic tissue
      were quantified at the end of the feeding interval. For Watanabe rabbits fed
      regular chow, the expression of both TGF-beta 1 and beta 2 is reduced in the
      aortic arch as compared with the descending aorta. In contrast, Watanabe rabbits
      fed high cholesterol diets manifested a differential expression of TGF-beta
      isoforms depending on the spatial location within the aorta. In the aortic arch,
      increased transcript signals for both TGF-beta 1 and beta 2 were noted as
      compared with rabbits on normal chow. The lesions found in the aortic arch are
      typified by abundant foam cells and proliferating smooth muscle cells. Analysis
      of the TGF-beta 1 and 2 profile on these same cell elements in vitro results in a
      similar expression of increased mRNA isoforms for TGF-beta 1 and 2.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8580373
TI  - LPS-induced release of EGF, GM-CSF, GRO alpha, LIF, MIP-1 alpha and PDGF-AB in
      PBMC from persons with high or low levels of HDL lipoprotein.
AB  - We have examined basal and lipopolysaccharide (LPS)-induced release of epidermal
      growth factor (EGF), granulocyte-macrophage colony-stimulating factor (GM-CSF),
      growth-regulated peptide alpha (GRO alpha), leukaemia inhibitory factor (LIF),
      macrophage inflammatory protein-1a (MIP-1 alpha) and platelet-derived growth
      factor-AB (PDGF-AB) in peripheral blood mononuclear cells (PBMC) from 20 persons
      with either high (n = 10) or low (n = 10) levels of high-density lipoprotein
      (HDL). PBMC were incubated with 100 ng LPS/ml for up to 160 h, and showed a
      significantly higher release of the chemokines GRO alpha (P = 0.04) and MIP-1
      alpha (P < 0.01) in persons with high HDL, whereas levels of GM-CSF were similar.
      Levels of EGF, LIF and PDGF-AB were always low, and remained unaltered during 160
      h of incubation. These findings indicate that PBMC from persons with high or low
      levels of HDL have different functional properties, of importance in cell
      recruitment and activation.

PMID- 8580374
TI  - Proinflammatory cytokine expression in cervicovaginal secretions of normal and
      HIV-infected women.
AB  - Proinflammatory cytokines may stimulate replication and spread of HIV. To
      evaluate to what extent the female genital tract represents a source of these
      cytokines, we determined TNF-alpha, IL-1 beta and IL-6 concentrations in paired
      serum and cervicovaginal washings from 45 HIV-negative and 50 HIV-positive women,
      and then we looked for the relevant mRNAs in cervicovaginal secretions by RT-PCR.
      Cytokines were detected by ELISA in cervicovaginal fluid from most healthy women.
      Cervicovaginal washing levels of TNF-alpha were increased above the control value
      +2 SD in 11/50 HIV-positive women, those of IL-1 beta in 13/50, and those of IL-6
      in 14/50. The prevalences of TNF-alpha, IL-1 beta and IL-6 increase and their
      levels in cervicovaginal washings were significantly higher in the 20 patients at
      stage IV than in the 30 patients at earlier stages of the disease. In HIV
      infected patients, serum and cervicovaginal washing levels correlated positively
      for TNF-alpha and IL-6, but not for IL-1 beta. Nine of 15 cytokine mRNAs
      determinations were positive in HIV-infected women versus 1 of 15 in controls (P
      < 0.01). These findings could be relevant to bidirectional heterosexual
      transmission of HIV.

PMID- 8580375
TI  - Expression of monocyte chemoattractant protein-1 in vascular tissue.
AB  - We investigated monocyte chemoattractant protein-1 (MCP-1) mRNA expression in rat
      vascular smooth muscle cells (VSMC) and in human atherosclerotic arteries to test
      the involvement of MCP-1 in the pathogenesis of atherosclerosis. In Northern blot
      analysis, MCP-1 mRNA expression was not observed in unstimulated cultured rat
      vascular smooth muscle cells (VSMC), but its expression was clearly observed by
      exposure to tumour necrosis factor-alpha (100 U/ml) for 2-6 h. Mitogen-activated
      protein kinase activity in VSMC incubated in serum-free culture medium was
      increased by exposure to 0.5% fetal bovine serum, while the effect was
      significantly suppressed in the presence of MCP-1 (100 ng/ml). We then evaluated
      MCP-1 mRNA expression in atherosclerotic arteries obtained from 12 patients
      undergoing bypass revascularization through reverse transcription-polymerase
      chain reaction analysis and observed MCP-1 mRNA expression in all atherosclerotic
      arteries studied. These results support the premise that MCP-1 is secreted by
      VSMC in atherosclerotic plaques as well as by endothelial cells and macrophages
      and contributes to the pathogenesis of atherosclerosis.

PMID- 8580376
TI  - Little expression of cytokine mRNA by fresh tumour-infiltrating mononuclear
      leukocytes from glioma and lung adenocarcinoma.
AB  - We investigated whether cytokine genes were activated in human tumour
      infiltrating mononuclear leukocytes (TIML) obtained from six lung adenocarcinomas
      and seven glioblastomas. TIML were extracted by mechanical disruption and
      isolated by double density gradient of Ficoll. We performed mRNA reverse
      transcription-polymerase chain reaction (RT-PCR) on these fresh (noncultured)
      TIML and autologous peripheral blood mononuclear leukocytes (PBML) using primers
      for the cytokines IL-1 beta, IL-6, IL-2, IL-4, GM-CSF, IFN-gamma and TNF-beta. In
      addition, we compared patients' TIML and PBML populations with healthy normal and
      alpha-CD3 activated PBML as an optimally activated reference population. Gel
      bands of RT-PCR products were quantitated in relative units (RU) as a function of
      their size and intensity by computerized image-analysis. Lung and brain patients'
      TIML showed IL-1 beta and IL-6 cytokine mRNA expressed in the average of 2-log RU
      but not significantly different from autologous and normal healthy PBML. IL-2,
      IFN-gamma and TNF-beta also did not appear expressed in the TIML at higher levels
      than in autologous or healthy normal PBML. However in two thirds of patients,
      lung TIML could be distinguished from autologous PBML by specific expression of
      GM-CSF and from healthy normal PBML by expression of IL-4. Similarly, most brain
      TIML expressed mRNA significantly above healthy normal PBML for GM-CSF and IL-4.
      In comparison with alpha-CD3 activated healthy PBML, our results suggest that
      lung and brain TIML had detectable cytokine mRNA, but they seemed poorly
      activated in total number of genes and amount of cytokine mRNA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8580377
TI  - The evolution of haematopoietic cytokine/receptor complexes.
AB  - The evolutionary expansion of the haematopoietic cytokines and their receptors is
      characterized by the duplication of both cytokines and receptors. A systematic
      analysis of primary sequence homology indicates that receptors for gp130
      associated cytokines group into signal transducing and non-signal transducing
      receptors. This observation is consistent with the evolution of the interleukins
      6, 11 and 12, granulocyte colony stimulating factor (G-CSF), leukemia inhibitory
      factor (LIF), oncostatin M, and the ciliary neurotrophic factor complexes from a
      common ancestral complex which included a homodimer of gp130-like signalling
      receptors and an interleukin 6 receptor-like non-signalling receptor. Alterations
      in the components of the complex are proposed to have arisen by receptor
      duplication and divergence to allow signal transduction via a LIF receptor/gp130
      heterodimer, and loss of the non-signalling receptor component in the G-CSF and
      the LIF lineage. The short-chain haematopoietins and their receptors do not group
      clearly, although interleukins 4 and 13 grouped together, as did 2 and 10.
      Internal duplication of the ligand-binding domain appears to have occurred
      independently in three separate lineages. These observations have implications
      for the classification of cytokines and receptors, and for the modelling by
      homology of their structures and interactions.

PMID- 8580378
TI  - Activation of JAK3, but not JAK1, is critical for IL-2-induced proliferation and
      STAT5 recruitment by a COOH-terminal region of the IL-2 receptor beta-chain.
AB  - A number of cytokines and growth factors use the JAK-STAT pathway to signal from
      the cell membrane to the nucleus. While homodimerizing cytokine receptors may
      transmit signal via a single form of JAK (i.e. growth hormone receptors), several
      multicomponent cytokine receptors have been shown to require simultaneous
      activation of pairs of different JAK kinases (i.e. interferon receptors). Recent
      evidence for a preferential coupling of JAK3 to interleukin-2 receptor-gamma (IL
      2R gamma) and JAK1 to IL-2R beta supports the concept of heterotrans-activation
      of JAK1 and JAK3 caused by IL-2-induced heterodimerization of their receptor
      partners. The present study verified the ability of IL-2 to cause tyrosine
      phosphorylation and activation of JAK1 and JAK3, but demonstrated that IL-2
      stimulated JAK3 to a significantly larger extent than JAK1 in human T lymphocytes
      and the YT cell line. This conclusion was based upon several independent
      criteria, including more vigorous tyrosine phosphorylation of JAK3, more marked
      enzymatic activation of JAK3 as well as higher abundance of JAK3 in activated IL
      2 receptor complexes. Furthermore, when human IL-2R beta was stably expressed in
      murine BA/F3 cells, robust IL-2-induced proliferation and JAK3 activation
      occurred without detectable involvement of either JAK1, JAK2 or TYK2. We
      therefore propose that IL-2 receptor signal transduction does not depend on
      equimolar heterodimerization of JAK1 and JAK3 following IL-2-induced
      heterodimerization of IL-2R beta and IL-2R gamma. Nonetheless, a membrane
      proximal region of human IL-2R beta (Asn240-Leu335) was critical for JAK3
      activation, and the amount of JAK3 present in activated IL-2 receptor complexes
      increased with time, suggesting that stabilization of JAK3 binding to the
      receptor complex relies on both IL-2R beta and IL-2R gamma. Moreover, STAT5 was
      found to be the predominant STAT transcription factor used by IL-2 in human T
      cells, and specifically required a COOH-terminal region of IL-2R beta (Ser386
      Val525), while STAT5 recruitment was not correlated to activation of IL-2R gamma
      or JAK3.

PMID- 8580379
TI  - Dimerization of chimeric erythropoietin/75 kDa tumour necrosis factor (TNF)
      receptors transduces TNF signals: necessity for the 75 kDa-TNF receptor
      transmembrane domain.
AB  - We developed a transfection-based assay for evaluating human (h) Tumour Necrosis
      Factor receptor (TNF-R) activities in a rat/mouse T-cell hybridoma, viz. PC60.
      Here we report on the role of TNF-R75 cross-linking in induction of GM-CSF
      secretion and apoptosis. The effect of TNF-R75 dimerization, in contrast to
      trimerization, was analysed by replacing the extracellular domain of this
      receptor with the equivalent domain of the murine erythropoietin receptor (EPO
      R), which dimerizes upon ligand interaction. To determine the role of the
      transmembrane region in signal transduction, chimeric EPO-R/TNF-R75 were
      constructed in which the respective transmembrane domains were interchanged. The
      hybrid receptors were introduced into PC60hTNFR55 cells, which already expressed
      functional, transfected hTNF-R55. By this approach we demonstrated that dimerized
      chimeric EPO-R/TNF-R75 receptors act synergistically with hTNF-R55-induced
      cytokine production and apoptosis as does trimerized wild-type hTNF-R75. Dimeric
      triggering of these hybrid receptors with EPO alone was less efficient than
      trimerization of hTNF-R75. Furthermore, EPO-R/TNFR75 only responded to EPO when
      the matching transmembrane region of TNF-R75 was present. Our results also prove
      that the hTNF-R75 extracellular part per se is not required for signalling.
      Finally, our data indicate that the expression of chimeric EPO-R/TNF-R75 in
      PC60hTNF-R55 cells, regardless of the presence of the TNF-R75 transmembrane
      region, facilitates TNF-R55-dependent signal transduction leading to apoptosis.
      This means that introduction of the intracellular domain of hTNF-R75, even
      without triggering, is sufficient to promote hTNF-R55-dependent activities in
      PC60 cells.

PMID- 8580380
TI  - Role of prostaglandins E1, E2 and F2 alpha in the brain in interleukin 1 beta
      induced adrenocorticotropin secretion in the rat.
AB  - It is well known that interleukin (IL)-1 is a potent activator of the hypothalamo
      pituitary-adrenal axis in the rat. Many studies have reported that prostaglandins
      (PGs), especially PGE2, in the brain may mediate the IL-1 stimulation of
      corticotropin-releasing hormone release, which then leads to adrenocorticotropin
      (ACTH) secretion. However, a general consensus has yet to emerge regarding
      whether PGE2 is the only or the most important PG in the brain mediating IL-1
      induced ACTH secretion in the rat. To address this question, we examined the
      effect of intracerebroventricular (icv) administration of antisera against PGE1,
      PGE2 or PGF2 alpha, or normal rabbit serum on the ACTH response induced by an icv
      injection of IL-1 beta in the rat. Each antibody or normal rabbit serum (as the
      control) was given icv 15 min before an icv administration of human recombinant
      IL-1 beta (50 ng). IL-1 beta produced a significant rise in plasma ACTH levels,
      and this response was significantly suppressed by either of the three PG
      antibodies. Interestingly, the inhibitory effect of anti-PGE2 antibody seemed to
      be somewhat weaker than those of the other two antibodies. We conclude that not
      only PGE2 but also PGE1 and PGF2 alpha in the brain may mediate the IL-1 beta
      stimulation of ACTH secretion in the rat.

PMID- 8580381
TI  - The influence of E. coli implantation in axenic mice on cytokine production by
      peritoneal and bone marrow-derived macrophages.
AB  - To assess the involvement of bacterial microflora in the development of host
      defenses, we compared in vitro LPS-induced cytokine production by macrophages in
      germ-free and E. coli monoxenic mice. E. coli implantation significantly
      increased IL-1 and IL-6 and, to a lesser extent, TNF activities of peritoneal and
      bone marrow-derived macrophages. These results suggest that exposure to
      microflora primes macrophages for an enhanced cytokine production, which may
      contribute to the activation of the antiinfectious defense. The priming was not
      restricted to peritoneal macrophages but was associated with a more general
      effect of the flora since the enhanced response of bone marrow-derived
      macrophages indicates an effect on macrophage precursors. Furthermore, a higher
      ability of peritoneal macrophages to produce IL-1 in axenic and monoxenic mice
      was observed as compared to bone marrow-derived macrophages. In contrast, bone
      marrow-derived macrophages demonstrated a higher ability to produce IL-6 and TNF
      but only 3 weeks after bacterial administration.

PMID- 8580382
TI  - Involvement of interleukin 1 and tumour necrosis factor alpha as endogenous
      growth factors in human osteoblastic cells.
AB  - Normal human osteoblastic (OB) cells produce several haematopoietic factors,
      including IL-1, IL-6, PGE2 and TNF-alpha. However, it is unknown whether these
      factors play a role as autocrine mitogenic factors. We show here that some of
      these cytokines released by OB cells are endogenous growth factors for OB cells.
      Conditioned medium (CM) obtained from quiescent OB cells, dose-dependently
      stimulated OB cell proliferation, suggesting the production of autocrine growth
      factors by OB cells. Treatment with exogenous rhIL-1 and rhTNF-alpha increased OB
      cell growth. We found that neutralizing antibodies against IL-1 and TNF-alpha at
      concentrations that specifically inhibited the mitogenic activity of these
      cytokines, suppressed part of the mitogenic effect of CM on quiescent OB cells
      cultured at low or high density. In contrast, treatment of OB cells with
      indomethacin at a dose (10(-6) M) that inhibits endogenous prostaglandin
      production, increased OB cell proliferation in the presence or absence of CM,
      indicating that the mitogenic effect of CM on OB cells was not due to PGE2. In
      addition, exogenous recombinant human (rh)IL-6, or a specific neutralizing anti
      IL-6 antibody, did not affect the OB cell proliferation. The results indicate
      that, in contrast to PGE2 and IL-6, IL-1 and TNF-alpha released by OB cells act
      as endogenous mitogenic factors for human osteoblasts.

PMID- 8580383
TI  - Characterization of polymorphisms of an interleukin 1 receptor type 1 gene
      (IL1RI) promotor region (P2) and their relation to insulin-dependent diabetes
      mellitus (IDDM). The Danish Study Group of Diabetes in Childhood.
AB  - We have identified two PstI polymorphisms of the interleukin 1 receptor type I
      gene (IL1RI). One of these (RFLP-A) showed significant association to IDDM (P =
      0.027), whereas no difference between patients and control subjects was found for
      RFLP-B (p = 0.42). RFLP-A was physically mapped to the 5'UTR of the gene. We
      sequenced and analysed a 411 bp region of a putative promotor region (P2) around
      RFLP-A. RFLP-A was due to a C to T transition in exon 1B of the IL1RI gene. This
      single-base mutation did not affect any known transcription factor recognition
      sequence or the predicted secondary mRNA structure. In addition, we found two
      other single-base substitutions in more than one individual. Neither of these
      showed specific disease association or absolute linkage with the RFLP-A.

PMID- 8580385
TI  - In vivo and in vitro cytokine profiles and mononuclear cell subsets in Sicilian
      patients with active visceral leishmaniasis.
AB  - Sera from Sicilian patients with confirmed visceral leishmaniasis (Leishmania
      donovani infantum) were analysed at the moment of the diagnosis, during the
      course of the disease and after clinical recovery, for the concentration of IL
      10, IFN-gamma, IL-4 and IL-2. The results show high concentrations of IL-10 and
      IFN-gamma in the sera at the beginning of infection that return to the normal
      range following successful chemotherapy. By contrast, PBMC stimulated in vitro
      with Ag and mitogen produced low levels of IL-10 and IFN-gamma when collected at
      the time of the diagnosis and normal levels when assayed after recovery. IL-2 was
      undetected in the sera and was significantly reduced in the supernatants of
      actively infected patients, returning to the normal level after recovery. IL-4
      was absent in the sera and in high concentrations in the supernatants in all the
      phases of the disease. The levels of CD4+ and CD8+ T cells were within the normal
      range, but acute VL patients had markedly reduced levels of memory T cells
      (CD3+/CD45RO+) compared with healthy controls. These cells returned to the normal
      levels following successful chemotherapy. T cells are strongly activated in acute
      VL patients as indicated by the elevated number of CD3+ HLA-DR+ and by the
      increase in HLA-DR antigen on these cells. There was a significant reduction in
      the cell membrane DR antigen of the monocytes (CD 14+) during the acute phase of
      the disease, but it returned to the normal range after clinical recovery. These
      findings therefore suggest that in Sicilian patients with active VL the cytokine
      profile is not clearly characterized by Th2 phenotype as in mice, and both Th1
      like and Th2-like cells appear to proliferate and to be activated. Furthermore,
      IL-10, rather than IL-4, could play an important part in the inhibition of IFN
      gamma-induced macrophage activation and could reflect the levels of HLA-DR
      antigen expressed by the monocytes.

PMID- 8580384
TI  - Induction of circulating interleukin 10 by interleukin 1 and interleukin 2, but
      not interleukin 6 immunotherapy.
AB  - The objective of this study was to investigate the in vivo production of
      interleukin 10 (IL-10) in cancer patients undergoing immunotherapy with IL-1
      alpha, IL-2 or IL-6 and to study the effect of the same cytokines on the in vitro
      synthesis of IL-10 by human monocytes and macrophages. In the IL-1 alpha clinical
      trial, patients received 0.03 g/kg of IL-1 alpha as a 30 minute infusion daily
      for 5 consecutive days. In these patients, plasma IL-10 levels rose rapidly and
      peaked within 1 h (121 +/- 16 pg/mL; n = 4) after the first IL-1 alpha infusion.
      Thereafter, the levels rapidly declined to baseline within 8 h. The peak plasma
      IL-10 levels measured on days 3 and 5 of therapy were somewhat less pronounced
      than those on day 1. IL-2 immunotherapy was also associated with the induction of
      circulating IL-10. These patients were treated with high-dose (6 x 10(5) IU/kg)
      IL-2 every 8 h for 5 consecutive days. IL-10 was detectable in these patients
      within 2-4 h after the first IL-2 infusion (105 +/- 12 pg/mL). In contrast to the
      transient bursts of IL-10 detected in patients treated with IL-1 alpha, IL-10
      levels progressively increased throughout the treatment course in the IL-2
      treated patients reaching peak levels on day 5 (240 +/- 22 pg/mL; n = 10). IL-6
      immunotherapy with a 5-day continuous infusion was not associated with detectable
      levels of circulating IL-10. Peripheral blood mononuclear cells and in vitro
      derived macrophages synthesized similar amounts of IL-10 after stimulation with
      IL-1 alpha or IL-2, but were unresponsive to IL-6. These results suggest that the
      proinflammatory cytokines IL-1 alpha and IL-2 induce the anti-inflammatory
      cytokine IL-10 in vitro and in vivo, whereas Il-6 is not able to stimulate IL-10
      synthesis.

PMID- 8580386
TI  - Interleukin 8-related neutrophil elastase and the severity of the adult
      respiratory distress syndrome.
AB  - The interaction between activated neutrophils and pulmonary endothelium is
      thought to contribute to the pathogenesis of the adult respiratory distress
      syndrome (ARDS), but its relation to ARDS severity, which may support a
      pathogenetic role, is unclear. Therefore, circulating inflammatory mediators,
      including the neutrophil chemoattractant and activator interleukin 8 (IL-8), the
      acute phase cytokine IL-6, and the neutrophil product elastase complexed to alpha
      1-antitrypsin (alpha 1-AT), were measured prospectively, together with gas
      exchange, ventilatory and radiographic variables, in 13 mechanically ventilated
      patients with ARDS, mostly owing to sepsis, at admission into the intensive care
      unit. Measurements were repeated in the eight improving patients at the time that
      positive end-expiratory pressure could be reduced to 0 cm H2O. From the gas
      exchange, ventilatory and radiographic abnormalities, a lung injury score (LIS)
      was calculated. For pooled data, the LIS and the arterial PO2/inspiratory O2
      fraction, the oxygenation ratio, correlated with plasma levels of IL-8 (rs =
      0.60, P < 0.01 and rs = -0.65, P < 0.005, respectively), with levels of IL-6 (rs
      = 0.60, P < 0.01, and rs = -0.68, P < 0.005, respectively), and the oxygenation
      ratio related to elastase-alpha 1-AT (rs = -0.70, P < 0.005). Levels of IL-8 and
      IL-6 interrelated (rs = 0.61, P < 0.01) and related to the elastase complexes (rs
      = 0.45, P < 0.05). Hence, our data support a role of cytokine-induced activation
      of neutrophils in the clinical severity of ARDS.

PMID- 8580388
TI  - Acute effects of fluoxetine versus placebo on functional health and well-being in
      late-life depression.
AB  - In a randomized 6-week trial comparing fluoxetine with placebo, the Medical
      Outcomes Study 36-Item Short-Form Health Status Survey (SF-36) scales were used
      to measure the effects of treatment on functional health and well-being among
      elderly (age > or = 60 years) outpatients with major depression. In the
      fluoxetine and placebo groups, 261 and 271 patients, respectively, completed the
      SF-36 before treatment and at Weeks 3 and 6. Compared with national norms for
      individuals over age 60, study patients before treatment exhibited baseline
      decrements on the following SF-36 scales: mental health, role limitations due to
      emotional problems, social functioning, vitality, role limitations due to
      physical problems, and bodily pain. Analyses of SF-36 changed scores from
      baseline to Week 6 revealed that the fluoxetine group improved more than the
      placebo group across all scales. Differences in changes of scores between groups
      were significant (p < .05), favoring the fluoxetine group for the scales of
      mental health, role limitations due to emotional problems, physical functioning,
      and bodily pain. Improvements observed in the fluoxetine group were both
      clinically and socially significant.

PMID- 8580387
TI  - Late-life delusional depression: acute and long-term treatment.
AB  - Treatment studies of delusional major depression demonstrate a poor response to
      standard antidepressant medications. Longitudinal studies demonstrate high
      relapse rates, even in patients receiving postdischarge antidepressants. The poor
      medical and psychiatric outcomes for late-life delusional depression and the
      increased risk for adverse medication reactions in this population underscore the
      importance of developing effective postrecovery treatments. Studies of mixed-age
      adults demonstrate the effectiveness of acute treatment with either
      electroconvulsive therapy or combination pharmacotherapy with high doses of
      neuroleptics and antidepressants. In considering these results in relation to the
      treatment of late-life delusional depression, attention must be given to the
      particular vulnerabilities to medication side effects of elderly patients. The
      potential effectiveness of continuation treatment with combined antidepressant
      neuroleptic therapy is discussed. Clinical and methodologic issues related to
      studying the effectiveness of combination treatment in elderly patients are
      emphasized.

PMID- 8580389
TI  - Research directions for treatment of depression.

PMID- 8580390
TI  - Maintenance therapies for late-life recurrent major depression: research and
      review circa 1995.
AB  - Major depression in the elderly is often a relapsing, chronic illness with high
      risk for chronic invalidism, poor treatment compliance, and suicide. In most
      cases, maintenance treatment to prevent recurrence and to enhance the quality of
      life is thought to be indicated. We review recent data from our ongoing studies
      that support both the efficacy and the safety of pharmacotherapeutic and
      psychotherapeutic maintenance treatments. However, the challenges of conducting
      maintenance therapy research (particularly with a placebo control) with the
      elderly are many, involving such areas as recruitment, retention, compliance,
      choice of outcome measures, and informed consent. We discuss each of these
      challenges and our responses to them. Finally, we suggest that maintenance
      therapy trials should be extended in several directions: (a) long-term treatment
      of bipolar and delusional subtypes in the elderly, as well as depression
      associated with progressive neurodegenerative disorders such as Alzheimer's
      dementia; (b) assessment of the benefits and risks of long-term therapy with
      other than tricyclic and monoamine oxidase inhibitor antidepressant agents, such
      as selective serotonin reuptake inhibitors; and (c) development of models of long
      term course, including the interaction of treatments with medical and
      psychosocial variables that can have a profound impact on illness onset and
      offset. These issues are illustrated with a discussion of a new protocol designed
      to test the acute and maintenance efficacy of antidepressant therapy for
      depressed patients with Alzheimer's disease.

PMID- 8580391
TI  - Clinical response predictors in a double-blind, placebo-controlled trial of
      fluoxetine for geriatric major depression. Fluoxetine Collaborative Study Group.
AB  - BACKGROUND: We attempted to determine baseline characteristics predicting
      response in a 6-week, double-blind, geriatric depression trial, which showed a
      significantly higher remission rate for fluoxetine (20 mg daily) than for placebo
      (31.6% vs. 18.6%, p < .001). METHODS: Outpatients (N = 671) were 60 years or
      older (mean +/- SD = 67.7 +/- 5.7), met Diagnostic and Statistical Manual of
      Mental Disorders (3rd ed., rev., American Psychiatric Association, 1987) criteria
      for unipolar major depression, had baseline scores on the 17-item Hamilton
      Depression Rating Scale (HAMD17) of 16 or more, and were randomized after a 1
      week placebo lead-in. Potential baseline predictors of percentage change in last
      visit-carried-forward HAMD21 total scores were entered into a stepwise regression
      model. The sample was randomly divided into two groups (development and
      validation data sets) so that potential predictors could be confirmed in a second
      analysis. RESULTS: Of the 266 variables considered for their prognostic ability,
      13 were found to be significant predictors using the development data set,
      including (a) presence of somatic complaints, absence of agitation, and presence
      of previous accidental injury for fluoxetine response; and (b) reported feelings
      of emptiness, absence of somatic complaints, and absence of early insomnia for
      placebo response. The second analysis using the validation data set failed to
      confirm statistical significance of predictors identified in the development data
      set. CONCLUSIONS: Although potentially useful baseline characteristics were
      initially identified as response predictors, conservative statistical methods
      failed to confirm any significant predictors of differential responses between
      fluoxetine and placebo in this double-blind, placebo-controlled trial. These
      results suggest that response predictor analyses require confirmation before
      conclusions can be generalized.

PMID- 8580392
TI  - Antidepressants in geriatric depression: what difference have they made?
AB  - This article reviews the evidence that antidepressants have improved the
      prognosis of geriatric depression. It examines studies carried out in the acute,
      continuation, and maintenance stages of treatment. Naturalistic studies carried
      out after the introduction of electroconvulsive therapy indicate that about one
      quarter of patients with major depression in later life remain symptom-free,
      approximately one third experience at least one relapse but with further
      recovery, and the remainder have residual symptoms. In about 10% of all cases,
      depressive symptoms remain severe and intractable. These proportions appear to
      have altered little since tricyclic antidepressants became available, although
      recent research into drug prophylaxis suggests that better outcomes may be
      possible. The article reviews some of the methodological problems that research
      workers must address. The role of newer antidepressants in prognosis is also
      discussed.

PMID- 8580393
TI  - Long-term prognosis of major depression in old age: a comparison with prognosis
      of dysthymic disorder.
AB  - The 5-year prognosis of 42 elderly patients with major depression (mean age 73.2
      +/- 6.3 years for men and 73.0 +/- 7.3 years for women) is described.
      Furthermore, the clinical outcome of elderly patients with major depression is
      compared to that of 199 elderly patients with dysthymic disorder (mean age 69.9
      +/- 7.2 years for men and 71.3 +/- 7.7 years for women) described in a previous
      article. Twelve percent of patients with major depression recovered, 26% still
      had depression after 5 years, 12% had possible dementia, 45% had died, and 5%
      could not be contacted. The outcome did not significantly differ between the
      sexes or the two age groups (65-74 and 75+). A poor clinical outcome of patients
      with major depression was related to a greater number of diagnosed diseases,
      strong feelings of restlessness, and higher sexual interest at the beginning of
      the follow-up. A poor prognosis was also found for the patients whose functional
      abilities and hobby activities declined during the follow-up. A poor prognosis
      tended to be related to absence of hypertension, frequent trembling of hands, low
      activity in listening to music, and high activity in watching TV at the onset,
      and to absence of malignant disease and occurrence of a high number of negative
      and positive life events during the follow-up period. Thirty-six percent of
      dysthymic patients recovered, 26% still had depression after 5 years, 9% had
      possible dementia, 25% had died and 4% could not be contacted. The outcome of
      dysthymic patients did not significantly differ between the sexes or the two age
      groups (65-74 and 75+). The clinical outcome of dysthymic patients tended to be
      more favorable than that of patients with major depression. The factors related
      to a poor outcome differed between patients with major depression and dysthymic
      patients.

PMID- 8580395
TI  - Treatment-resistant depression in the elderly.
AB  - Apparent treatment-resistant depression (TRD) is frequently encountered by and
      poses particular challenges for the old-age psychiatrist. The prevalence of true
      nonresponse to treatment is not known with accuracy but reports put it at 18% to
      40% for the elderly. This article reviews the concept of TRD in the elderly,
      discussing the factors involved in apparent resistance and the treatment of this
      group. We suggest that absolute TRD may be a rarer entity than the estimated 18%
      to 40% if depressed patients are treated carefully and vigorously.

PMID- 8580394
TI  - Efficacy of acute treatment for geriatric depression.
AB  - The antidepressant literature for depression in late life tends to be interpreted
      as saying that certain antidepressant medications--e.g, nortriptyline, doxepin,
      fluoxetine--have fewer and milder side effects than others, whereas overall
      efficacy is equivalent (Plotkin et al., 1987; Rush, 1993; Salzman et al., 1995;
      Schneider, 1994). Further examination of this literature, however, suggests that
      both efficacy and side effect rates for any particular medication vary among
      trials, and often depend on the medications being compared, the use of placebo,
      the dose, and the design of the trial. In this report we review selected clinical
      trials, and summarize and discuss a previously published meta-analysis. Treatment
      recommendations from the 1991 NIH Consensus Development Conference on the
      Diagnosis and Treatment of Depression in Late Life and from the Agency for Health
      Care Policy Research are discussed. Directions for future research are suggested.
      Both antidepressant medications and brief structured psychotherapies have
      efficacy in the acute treatment of elderly depressed outpatients with major
      unipolar, nondelusional depression. Effective treatment for depression involves
      consideration of the type and severity of illness, adequate prescribing, patient
      education, and regular patient monitoring for compliance, symptom change, side
      effects, and intercurrent medical disorders, which may complicate antidepressant
      therapy.

PMID- 8580396
TI  - The difficult elderly patient: curable hostile depression or personality
      disorder?
AB  - The aim of this article is to suggest that hostile behavior in elderly patients
      is often caused by a reversible mood disorder rather than by a personality
      disorder or dementia, even if these two last diagnoses are already well
      established. Sedatives, often prescribed for hostile behavior, can induce
      confusion, falls, and bedridden states, and can actually increase the rate of
      mortality. The mood disorder can be a hostile agitated depression or a mixed
      affective state. The hypothesis of a mood disorder calls for an antidepressant
      trial, possibly combined with a mood stabilizer.

PMID- 8580397
TI  - The effect of three H2 receptor antagonists on the disposition of cyclosporin A
      in the in situ perfused rat liver model.
AB  - The in situ perfused rat liver model was used to investigate the effect of three
      H2 receptor antagonists on the disposition of cyclosporin A (CyA) and the major
      human metabolite, AM1. Perfusion experiments, using standard techniques, were
      carried out on four groups (one control and three H2-receptor antagonist-treated
      groups) of male Sprague-Dawley rats (300-350 g). All animals received CyA, 2.5
      mg; the three treated groups received cimetidine (8 mg), ranitidine (3 mg), or
      famotidine (0.4 mg). Perfusate and bile samples were collected and assayed for
      CyA, AM1, and the H2 receptor antagonists by HPLC. Results indicated that CyA
      perfusate concentrations in the controls and cimetidine and ranitidine-treated
      groups were not significantly different, although levels in the famotidine group
      were significantly higher at all times (p < 0.05), except 30 min, compared to the
      controls. However, examination of the AM1 perfusate and bile data and the
      apparent metabolic clearance data indicated that CyA metabolism was still
      occurring, despite the presence of the H2 receptor antagonist. It is suggested
      that the absence of a interaction may be attributed to a lack of specificity of
      the H2 receptor antagonists for CYP3A, the isoenzyme responsible for CyA
      metabolism.

PMID- 8580398
TI  - Interspecies pharmacokinetic scaling of BSH in mice, rats, rabbits, and humans.
AB  - Sodium mercaptoundecahydrododecaborate or BSH is an important compound for boron
      neutron capture therapy (BNCT). The total clearance and steady state volume of
      distribution of BSH in humans and in laboratory animals were analyzed as a
      function of species body weight using the allometric equation for interspecies
      scaling. Significant linear relationships were obtained between log CLt (Lh-1)
      and log W (kg) (r = 0.972; p = 0.028) as well as log VSS (L) and log W (kg) (r =
      0.999; p = 0.0005). The corresponding allometric equations were CLt = 0.127 W0.68
      and VSS = 1.557 W0.87, respectively. BSH clearance in various species was shown
      to be a constant fraction (0.26) of creatinine clearance, the relationship being
      independent of body weight. Thus BSH clearance in various species occurred at
      similar pace when measured by a physiological parameter (creatinine clearance)
      rather than chronological time. Interspecies scale-up of plasma concentration
      time data for the four species using a complex Dedrick plot resulted in similar
      profiles. Our results indicate that the BSH data obtained in laboratory animals
      could be utilized to generate preliminary estimates of the pharmacokinetic
      parameters in humans. These parameters can serve as guidelines for better
      planning of clinical studies.

PMID- 8580399
TI  - Antibronchospasmic, tachycardiac, and hypokalaemic effects of L-isoproterenol in
      guinea-pigs.
AB  - The relationship between antibronchospasmic, tachycardiac, or hypokalaemic
      effects and plasma concentration of L-isoproterenol (ISP) hydrochloride was
      investigated in guinea-pigs in vivo. ISP was infused at the rate of 10, 30, 50,
      100, and 300 ng kg-1 min-1. The antibronchospasmic effect was expressed as the
      attenuation of methacholine-induced bronchospasm. The EC50 values of ISP for
      antibronchospasmic and tachycardiac effects were 5.12 nM and 3.95 nM,
      respectively. Although they were comparable to the values reported in vitro (7.23
      0.358 nM, 1.77 nM), the concentration response relationship of ISP for
      antibronchospasmic effect was quite steep with a slope factor of more than six.
      Moreover, a decrease in plasma potassium level was not clearly detected. The
      experimental procedure in our present study was useful for evaluating
      antibronchospasmic and tachycardiac effects of beta-agonists.

PMID- 8580400
TI  - Enantioselective pharmacokinetics in animals of pazinaclone, a new isoindoline
      anxiolytic, and its active metabolite.
AB  - The enantioselective pharmacokinetics of a new anxiolytic, pazinaclone (DN-2327),
      and its active metabolite, M-II, were studied in animals. In rats and dogs given
      racemic pazinaclone intravenously, the total clearance and volume of distribution
      of (S)-pazinaclone were lower than those of (R)-pazinaclone, whereas the opposite
      results were obtained in monkeys. The differences in disposition were consistent
      with enantioselective protein binding, where the unbound fraction was greater for
      (R)-pazinaclone than that for the (S)-enantiomer in rats and dogs; the reverse
      was noted in monkeys. Lower clearance and distribution for (S)-pazinaclone in
      rats and dogs, and for the (R)-enantiomer in monkeys, resulted in comparable
      plasma profiles for the pazinaclone enantiomers and thereby those of the
      corresponding enantiomers of M-II. The unbound clearance (CLu) of (S)-pazinaclone
      was, however, greater than that of the antipode in rats and dogs and the CLu of
      each enantiomer was similar in monkeys. Thus, enantioselectivity in the kinetics
      of (S)- and (R)-pazinaclone appears to reside largely in plasma binding
      differences and is unrelated to variations in intrinsic clearance. The first-pass
      metabolism of (S)- and (R)-pazinaclone on oral administration of the racemate was
      enantioselective, with respective bioavailabilities of 1.7 and 0.8% in rats, 10.4
      and 1.9% in dogs, and 0 and 11.4% in monkeys. Therefore, the enantioselectivity
      was more pronounced after oral dosing.

PMID- 8580401
TI  - Factors influencing the protein binding of YH-439 using an equilibrium dialysis
      technique. A new hepatoprotective agent.
AB  - Various factors influencing the plasma protein binding of YH-439 to 4% human
      serum albumin (HSA) were evaluated using the equilibrium dialysis method at the
      initial YH-439 concentration of 2 micrograms mL-1. It took approximately 12 h of
      incubation to reach an equilibrium between 4% HSA and isotonic phosphate buffer
      of pH 7.4 containing 3% of dextran ('the buffer') using a Spectra/Por 2 membrane
      (molecular weight cut-off, 12,000-14,000) in a water bath shaker kept at 37
      degrees C and at a rate of 50 oscillations min-1. YH-439 was fairly stable both
      in 4% HSA and in the 'buffer' for up to 24 h incubation. The binding of YH-439 to
      4% HSA was constant (97.4 +/- 0.55%) at YH-439 concentrations ranging from 0.5 to
      10 micrograms mL-1. However, the extent of binding was dependent on HSA
      concentrations: the values were 90.7, 94.7, 96.7, 97.0, 97.0, 97.1, and 97.5% at
      HSA concentrations of 0.5, 1, 2, 3, 4, 5, and 6%, respectively. The plasma
      protein binding decreased with increasing incubation temperature: the binding
      values were 98.2, 97.6, 97.2, and 96.8% when incubated at 10, 21, 26, and 37
      degrees C, respectively. The binding of YH-439 was also influenced by the
      chloride concentration in the buffer: the binding values were 94.5, 97.0, and
      96.8% for the chloride concentrations of 0, 0.249, and 0.546%, respectively. The
      binding of YH-439 was also dependent on the buffer pH: the percentages of free
      fraction were 6.0, 4.1, 3.8, 2.8, 2.7 and 2.8% for the buffer pHs of 5.0, 6.0,
      6.5, 7.0, 7.4, and 8.0, respectively. The free fraction of YH-439 was slightly
      increased by the addition of heparin (up to 40 U mL-1), sodium azide (NaN3, up to
      0.5%), and its metabolites. The protein binding of YH-439 was influenced neither
      by AAG, acetylsalicylic acid, or sulphisoxazole, nor by the addition of citrate
      or EDTA. The free fractions of YH-439 in rabbit (4.2%) and dog (4.7%) plasma
      seemed to be higher than in rats (2.9%) and humans (3.1%).

PMID- 8580402
TI  - The ratio of first to zeroth moments of the plasma profile of an oral drug
      undergoing first-pass and linear reversible metabolism.
AB  - Based on the convolution integral, equations have been derived for the ratio of
      the first to the zeroth moments of the plasma concentration-time curve (AUMC/AUC)
      parameters for a drug (p) undergoing first-pass and reversible metabolism and its
      reversible metabolite (m). According to these equations, the AUMC/AUC of a drug
      administered orally and of its reversible metabolite can be related to the mean
      absorption times, the ratios of the fraction of the dose entering the systemic
      circulation to the bioavailability, the first-time fractional conversion of each
      compound, and the AUMC/AUC ratios after intravenous administration of each
      compound. The proposed approach allows a more generalized derivation method for
      AUMC/AUC of a drug administered orally and undergoing first-pass and reversible
      metabolism. It is also applicable to any other extravascular route.

PMID- 8580403
TI  - Bile acid-induced depolarization of mitochondrial membrane potential preceding
      cell injury in cultured gastric mucosal cells.
AB  - Changes in energy metabolism elicited by sodium taurocholate and their relation
      to cell viability were determined in gastric mucosal cells. Cultured mucosal
      cells were labelled with rhodamine-123, a mitochondrial energization-sensitive
      fluorescence probe, or by propidium iodide, a fluorochrome which labels the
      nuclei of non-viable cells. The cells were observed under a fluorescence
      microscope with a laser scanning confocal imaging system. After the addition of
      sodium taurocholate at concentrations > 5 mol/L, mucosal cells showed a rapid and
      significant decrease in rhodamine-123 fluorescence. A decrease to 40% of the
      pretreated values at 30 min was seen with a concentration of sodium taurocholate
      of 7.5mmol/L. A marked increase in the percentage of propidium iodide-positive
      cells was noted when the concentration of sodium taurocholate exceeded 5mmol/L.
      However, the extent of the decrease in rhodamine-123 fluorescence was always
      greater than the increase in the percentage of propidium iodide-positive cells,
      suggesting that most of these gastric mucosal cells remained viable. It is
      therefore suggested that the decrease in rhodamine-123 fluorescence is largely
      due to the disturbed oxidative phosphorylation of mitochondria. Pretreatment of
      gastric mucosal cells with low concentrations of ethanol resulted in a
      significant cytoprotective effect against sodium taurocholate injury with
      significant prevention of a decrease in rhodamine-123 fluorescence. It is
      concluded that sodium taurocholate induces a depolarization of the mitochondrial
      membrane potential preceding cell injury and that the cytoprotective effect of
      ethanol relates to its attenuation of the uncoupling effect.

PMID- 8580404
TI  - Basic fibroblast growth factor accelerates gastric mucosal restoration in vitro
      by promoting mesenchymal cell migration and proliferation.
AB  - It has been generally accepted that basic fibroblast growth factor is a potent
      stimulator of duodenal ulcer healing. However, the detailed mechanism and mode of
      action of growth factor on gastric ulcer healing is still controversial.
      Therefore, in the present study, the effects of basic fibroblast growth factor on
      gastric mucosal repair were studied using an in vitro cultured cell system.
      Artificial wounds were made in confluent monolayer rabbit gastric fibroblast and
      epithelial cell sheets by mechanical denudation. Changes in the size of the cell
      free area were analysed quantitatively. Cell proliferation was assessed by BrdU
      staining. For both cell types, mucosal restoration involved cell migration and
      proliferation. Although the speed of restoration of epithelial cells was not
      affected by the addition of basic fibroblast growth factor, it was much faster
      for epithelial cells than for fibroblasts. Basic fibroblast growth factor
      accelerated wound repair of fibroblasts but not epithelial cells. Basic
      fibroblast growth factor accelerated wound repair by stimulating both cell
      migration and proliferation. Therefore, the effects of basic fibroblast growth
      factor in peptic ulcer diseases may be mainly due to the stimulation of
      mesenchymal cells.

PMID- 8580405
TI  - Dyspepsia and Helicobacter pylori in Japanese employees with and without ulcer
      history.
AB  - In a Dutch working population, the apparent association between dyspeptic
      symptoms and Helicobacter pylori infection was found to be entirely due to
      subjects with an ulcer history. In general populations with a much higher
      prevalence of H. pylori infection and peptic ulcer disease, such as in Japan, the
      relationship between dyspepsia and H. pylori has yet to be clarified. A
      questionnaire on ulcer history and dyspeptic symptoms during the preceding 3
      month period was obtained from apparently healthy Japanese employees who
      underwent a periodic medical examination. In addition, serum samples were
      analysed for anti-H. pylori IgG antibodies. A total of 196 men and 35 women, aged
      23-71 years, participated in the study. Seven women (20%) and 49 men (25%) had a
      diagnosis of peptic ulcer disease. Among 41 subjects with verified duodenal (26)
      and/or gastric (17) ulcer, 95% were H. pylori positive while 32% had had frequent
      dyspeptic symptoms in the 3 months prior to the study (29% of the 35 men and 50%
      of the 6 women). Among the 147 men and 28 women without an ulcer history, the 3
      month period prevalence of frequent dyspepsia was 14 and 32%, respectively. The
      rate of H. pylori positivity was 80% in non-ulcer dyspeptics and 68% in all other
      non-ulcer subjects (95% confidence intervals: 61-92 and 61-76%, respectively).
      Significant differences in symptoms between H. pylori positive and negative
      subjects could not be detected, neither in the whole population nor in the non
      ulcer group. In conclusion, in this Japanese working population, no association
      was found between dyspeptic symptoms and H. pylori infection, irrespective of the
      inclusion of subjects with a peptic ulcer history.

PMID- 8580406
TI  - The importance of the pylorus as a regulator of solid and liquid emptying from
      the stomach.
AB  - The role of the pylorus in the control of gastric emptying of liquids and
      digestible solids was investigated in the present study by pylorus excision in
      six pigs. The pylorus was left intact in another six pigs. Antro-pyloro-duodenal
      motility was recorded by a sleeve sensor and side holes. Liquid emptying was
      significantly more rapid in pylorus excised than in pylorus intact animals,
      during intraduodenal infusion of isosmolar dextrose (712 mL vs 107 mL), fatty
      acid (402 mL vs 46 mL), amino acids (752 mL vs 112 mL), 25% dextrose (392 mL vs
      51 mL) and 3 normal saline (705 mL vs 157 mL). In pylorus excised animals, in
      contrast to pylorus intact animals, the manometric pattern of isolated pyloric
      pressure waves at the distal stomach was rarely seen (P < 0.05). In a second
      series of experiments, pylorus excised animals emptied significantly more (P <
      0.04) meat over 120 min (181 g) than pylorus intact animals (80 g), but the
      proportion of particle sizes emptied was unaltered. In the pig, localized pyloric
      contractions are important for retardation of gastric emptying when nutrient or
      hyperosmolar solutions enter the duodenum. By contrast, the pylorus is
      unimportant in determining the size of solid particles emptied from the stomach.

PMID- 8580407
TI  - Aflatoxin and p53 abnormality in duck hepatocellular carcinoma.
AB  - Recent studies have revealed that a point mutation at codon 249 in the p53 gene
      predominates in hepatocellular carcinoma (HCC) cases from Southern Africa and
      China, where infection with hepatitis B virus (HBV) and contamination of
      aflatoxin B1 in food are risk factors for HCC. This unique mutation from G to T
      at the third base in codon 249 observed in human HCC cases is suggested to be
      linked to aflatoxin exposure. Six ducks with HCC, five of which were fed a diet
      containing aflatoxin B1 for 1-2 years, were analysed for the presence of point
      mutations at this codon of the p53 gene by polymerase chain reaction and direct
      nucleotide sequencing. None of the six ducks with HCC showed the change at this
      codon regardless of duck hepatitis B virus infection. This suggests that
      aflatoxin B1 itself might not be involved in the unique mutation at codon 249 in
      hepatocarcinogenesis, or that other factors coincident with aflatoxin may be
      responsible for this unique mutation.

PMID- 8580408
TI  - CD34 expression in endothelial cells of small hepatocellular carcinoma: its
      correlation with tumour progression and angiographic findings.
AB  - The angiogenic process plays an important role in tumour growth and metastasis
      during hepatocarcinogenesis, but it is still uncertain when the process begins
      during tumour formation. Forty-two small hepatocellular carcinomas (HCC) that
      measured either less than or equal to 2 cm in diameter were studied by comparing
      the histologic findings with the angiographic findings, and with
      immunohistochemical expression of endothelial marker QB-end/10 (QB), a new
      monoclonal antibody raised against CD34, in the sinusoidal wall. Twenty (91%) of
      22 moderately or poorly differentiated HCC revealed a positive reaction for QB,
      while only eight (40%) of 20 well differentiated HCC demonstrated a positive
      reaction (P < 0.01). In the tumours showing a 'nodule in nodule' appearance, the
      less differentiated areas were more reactive for QB. Twenty-three (82%) of 28 QB
      positive tumours were hypervascular, while only three of 14 (21%) QB negative
      tumours were hypervascular (P < 0.01) by angiography. All six of the poorly
      differentiated and 13 (81%) of the 16 moderately differentiated tumours were
      hypervascular, while only seven (35%) of 20 well differentiated HCC were
      hypervascular (P < 0.01). These results indicate that as the tumour becomes less
      differentiated, the QB positive areas become wider and angiography demonstrates
      hypervascularity. We therefore speculate that the HCC sinusoids acquire the
      characteristics of capillary and precapillary blood vessels during de
      differentiation from well to moderate, and thus the tumour begins to reveal
      hypervascularity on angiography. The above process may be correlated with the
      stepwise progression of HCC.

PMID- 8580409
TI  - Rat peripheral mononuclear cell thymidine kinase activity increases during liver
      regenerative processes after partial hepatectomy.
AB  - Deoxythymidine kinase (TK; EC 2.7.1.21) activity in the liver has been used as a
      marker of liver regeneration after partial hepatectomy. In this study we examined
      TK activity of various organs, plasma and peripheral blood mononuclear cells
      (PMNC) in 70% partially hepatectomized rats. TK activity of lymph nodes, small
      intestine, heart, lung, kidney and thymus did not increase significantly during
      the course of the study, except for spleen at 72 h. On the other hand, PMNC-TK
      and liver cystosolic TK activity increased in a parallel fashion at all times
      after partial hepatectomy; they began to increase 12 h after surgery and peaked
      48 h post-surgery. Fractionation of PMNC into T cells and B cells revealed that
      both populations increased and peaked 48 h post-surgery. Plasma TK peaked 12-24 h
      after surgery, then declined at 36, 48 and 72 h after partial hepatectomy. This
      change paralleled plasma levels of aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT). PMNC-TK activity correlated significantly with liver
      cystosolic TK activity 24 h (r = 0.743; P < 0.05) and 48 h (r = 0.708; P < 0.05)
      after partial hepatectomy. However, it did not correlate with plasma levels of
      TK, AST and ALT. The results indicate that in the early stage of liver
      regeneration PMNC-TK may provide a marker of liver regenerative processes.

PMID- 8580411
TI  - The importance of the pylorus in gastric emptying.

PMID- 8580410
TI  - Ultrasound-guided fine needle aspiration biopsy of portal vein thrombosis in
      liver cirrhosis: results in 15 patients.
AB  - Between 1988 and 1992 ultrasound-guided fine needle aspiration biopsies of
      thromboses in the main branches of the portal vein were carried out in 15
      patients with liver cirrhosis. The aims of the study were to evaluate the
      usefulness, feasibility and diagnostic accuracy of this procedure in cirrhotics
      with known or suspected hepatocellular carcinoma. The procedure was carried out
      only in patients with a platelet count > or = 40,000/microL and prothrombin
      activity > or = 40%. A single pass, with a 22 gauge spinal needle, was performed
      in the portal vein lumen. Diagnosis of the aetiology of the portal vein
      thrombosis was obtained in all 15 cases. In 12 cases, a cytological diagnosis of
      hepatocellular carcinoma was made. In one case, the neoplastic cells aspirated
      were compatible with adenocarcinoma, and a subsequent colonoscopy confirmed the
      presence of colonic cancer. The material aspirated was compatible with chemically
      induced thrombosis in one patient who had undergone several percutaneous ethanol
      injection sessions for treatment of hepatocellular carcinoma, and in the last
      case only blood was aspirated, thus ruling out the coexistence of hepatic cancer.
      We conclude that fine needle aspiration biopsy of portal vein thrombosis is a
      feasible, low risk procedure that facilitates the diagnosis of hepatocellular
      carcinoma when fine needle biopsy of focal liver lesions fails. Fine needle
      aspiration biopsy of portal vein thrombosis is also useful in excluding
      neoplastic aetiology of portal vein thrombosis.

PMID- 8580412
TI  - The long-term efficacy of interferon alfa in chronic hepatitis C patients: a
      critical review.
AB  - With current therapeutic regimens, sustained responses occur in no more than 25%
      of patients with chronic hepatitis C who are treated with interferon. Relapses
      occur usually within 6 months from therapy suspension, but clinical and virologic
      recurrencies can be observed as late as after 3 years of follow up. The rate of
      long-term responses seems to depend on the dosage and the period of
      administration of interferon, but the best therapeutic protocol remains unknown.
      As a direct marker of permanent recovery is not available, indirect signs of
      disease resolution are: (i) continuously normal alanine aminotransferase levels;
      (ii) clearance of HCV-RNA; (iii) disappearance of anti-C100/NS4; and (iv)
      significant histological improvements assessed at least 2 years after therapy
      withdrawal. Known baseline predictive features of long-term response are the
      absence of cirrhosis, low viraemic levels and infection with HCV of type III or
      IV genotype (Okamoto's classification). According to recent reports, the lower
      the heterogeneity of the hypervariable region of the envelope 2 gene of HCV, the
      higher the chance of a sustained remission. There is not yet any consensus on the
      efficacy of a second therapeutic course of interferon in inducing a permanent
      response, and controlled trials are needed to clarify this issue.

PMID- 8580413
TI  - Primary prevention of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the major cancers in China. Accordingly,
      the mortality rates in 1990 (per 100,000) were 20.10 in certain cities and 24.32
      in certain counties. More than 90% of HCC cases and 70% of controls were infected
      with the hepatitis B virus (HBV) (Odds Ratio (OR) = 10-50). In the same group of
      patients, 8-27% of those with HCC and 0-11% of the healthy controls were also
      infected with hepatitis C (HCV) (OR = 2.11-17.29). There appears to be some
      correlation between HBV markers and the OR. The government requires that 85% of
      infants be immunized with HBV vaccine. In 1992, there were 3 million infants
      inoculated with HB vaccines. Aflatoxins have been found as contaminants in food,
      particularly in corn, peanut oil, soya sauce and fermented soya beans. The intake
      of aflatoxin B1 (AFB1) by people of ten different villages correlated with HCC
      mortality rates (r = 0.55; P < 0.05). The concentration of AFB1-albumin adducts
      is an indicator of individual exposure to aflatoxins. These adducts are higher in
      hyperendemic HCC areas and cases. Most people have now changed their staple food
      and eat rice instead of corn. Six large epidemiological studies have confirmed
      that people who drink pond-ditch water experience higher HCC mortality rates than
      people who drink deep-well water. Recent research has found that the blue-green
      algal toxin microcystin (MCYST) was a contaminant of pond-ditch water. MCYST is a
      strong promoter of HCC and will induce severe intrahepatic haemorrhages and liver
      necrosis. More than 80% of people in Qidong County have already changed their
      sources of water from pond-ditches to deep wells. Therefore, a combined strategy
      of the prevention of hepatitis, control of crops and control of drinking water is
      advocated for the primary prevention of HCC in China.

PMID- 8580414
TI  - Secondary prevention of hepatocellular carcinoma.
AB  - Two decades have gone by since the earlier trials of alpha-fetoprotein (AFP)
      screening for hepatocellular carcinoma (HCC) were conducted in Africa and China.
      It is accepted that early detection, diagnosis and treatment of HCC remains an
      important target to be achieved before a breakthrough appears on the primary
      prevention of HCC. In the present study, screening investigations were performed
      in a high risk population of HCC, defined as persons who had hepatitis, blood
      transfusions, a family history of HCC, and were hepatitis B virus carriers.
      Ultrasonography combined with AFP serosurvey was accepted as an effective
      screening procedure to detect small HCC. Early diagnosis of HCC was not difficult
      if tumour markers and medical imaging were combined. Early resection has been
      proven to prolong survival of patients with small HCC. Repeated intralesional
      ethanol injection is an alternative treatment to surgery, while transcatheter
      arterial embolization is a less effective alternative. Re-resection of
      subclinical recurrence after curative resection has proven of merit in prolonging
      survival even further. Resection of small HCC remains an important approach in
      getting long-term HCC survival and to improving 5-year survival rates. It is more
      effective than treatment of large HCC. Studies on the secondary prevention of HCC
      have stimulated research into tumour markers, the natural history and cellular
      origin of HCC and oncogenes. However, the issue of 'cost-effectiveness' remains
      to be evaluated.

PMID- 8580415
TI  - Acute pancreatitis associated with brucellosis.
AB  - Acute pancreatitis developed in a patient with acute brucellosis due to Brucella
      melitensis. To the best of our knowledge this is only the second reported case of
      acute pancreatitis associated with Brucella infection.

PMID- 8580416
TI  - Cystic lymphangioma of the gall-bladder: a case report.
AB  - Intra-abdominal cystic lymphangiomas are rare lesions that can be difficult to
      diagnose. We present a report of a patient with a giant multilocular cystic
      lesion in the abdomen. Ultrasonography and computed tomography scans of the
      abdomen revealed that the cyst had originated in the gall-bladder fossa. There
      was some calcification and thickening of the cyst wall. Endoscopic retrograde
      cholangiopancreatography demonstrated a medially deviated common bile duct, an
      elongated cystic duct and an inferior compressed gallbladder. There was no
      apparent communication between the cyst and the biliary tract; however, an
      abdominal angiogram revealed that the lesion was supplied by a branch of the
      cystic artery. Histological findings obtained intra-operatively were consistent
      with a cystic lymphangioma. Its characteristic histology was observed in the
      subserous layer of the gall-bladder. This case is a rare instance of a cystic
      lymphangioma originating in the gall-bladder.

PMID- 8580417
TI  - Assessing working memory for objects in rats: no one said it was easy.

PMID- 8580418
TI  - The object delayed non-matching to sample task in rats does not depend on working
      memory.
AB  - Four rats were trained on an object delayed non-matching to sample task to
      measure working memory (WM). On separate trials a sample object was presented to
      the rat, which was presented again along with another object after a 3 s delay
      rats were rewarded with food if they chose the novel object. In this procedure
      the choice objects are positioned in a fixed order (the novel object was
      positioned at first, followed by the sample object). When the order of placement
      of the choice objects was reversed performance dropped from 87% to 28% correct,
      showing that the rats always chose the object that was first positioned into the
      choice area. When the order of positioning of the choice objects was randomized
      during training, rats were not able to learn the task. It is suggested that
      performance is based on a discrimination between choice objects instead of WM.

PMID- 8580419
TI  - Human muscle fatigue investigated by transcranial magnetic stimulation.
AB  - Corticospinal motor output was studied during a 1.5 min maximum isometric
      voluntary contraction of the first dorsal interosseous muscle in five healthy
      subjects. Compound muscle action potentials (CMAPs) evoked by suprathreshold
      magnetic cortical stimuli and by supramaximal ulnar nerve stimuli were compared.
      On average, force fell to 25% of its initial value, CMAPs from nerve stimuli
      declined to 58% of initial, but CMAPs from cortical stimuli showed no significant
      change in amplitude after the first 5 s. It is concluded that there is no marked
      net change in corticospinal output during fatigue. It is postulated that cortical
      stimuli engage a subgroup of low threshold, fatigue-resistant motor units which
      remain active throughout the contraction.

PMID- 8580420
TI  - How is direction selectivity organized in the extrastriate visual area PMLS of
      the cat?
AB  - Although most neurones in the PMLS of the cat are selective for direction of
      motion, whether the preferred directions are organized into cortical columns, as
      they are in the MT area of the monkey, is not certain. We have quantitatively
      investigated the organization of direction selectivity of PMLS neurones. The
      results showed that adjacent neurones have similar direction selectivity. The
      preferred direction of neurones sampled successively in a tangential penetration
      changed continually, occasionally with an approximately 180 degrees reversal, and
      neurones with bidirectional selectivity tended to be located in the reversal
      region. It is spectulated that direction selectivity in the PMLS is organized on
      the basis of preferred axis of motion in such a way that one column with
      bidirectional preference lies between two columns with opposite unidirectional
      preferences, a unidirectional column is always adjacent to a bidirectional column
      and these adjacent columns share a common preferred axis-of-motion.

PMID- 8580421
TI  - Ia boutons to CCN neurones and motoneurones are enriched with glutamate-like
      immunoreactivity.
AB  - The monosynaptic connection between muscle spindle Ia afferents and motoneurones
      is one of the most extensively studied reflex pathways in the central nervous
      system. Physiological evidence has pointed to glutamate as the fast transmitter
      in this synaptic connection. In this study of the spinal cord segment C2, we used
      dual labelling with cholera toxin subunit B-horseradish peroxidase (B-HRP) and
      postembedding immunohistochemistry to show that group Ia primary afferent boutons
      synapsing on retrogradely labelled central cervical nucleus (CCN) neurones and
      motoneurones are enriched in glutamate-like immunoreactivity (LI). All double
      labelled Ia terminals studied could be classified as S-type (CCN neurones and
      motoneurones) or M-type (motoneurones) boutons.

PMID- 8580422
TI  - Characterization of the antiallodynic efficacy of morphine in a model of
      neuropathic pain in rats.
AB  - Neuropathic pains have often been classified as opioid resistant. Here, the
      ability of systemic (i.p.), intracerebroventricular (i.c.v.) and intrathecal
      (i.th.) morphine to inhibit mechanical allodynia were studied in a nerve ligation
      (L5, L6 nerve roots) model of neuropathic pain in rats. Morphine administered
      i.p. or i.c.v. produced dose-dependent antiallodynia which was readily
      antagonized by naloxone (5 mg kg-1, i.p. at -10 min). In contrast, i.th. morphine
      at doses up to 100 micrograms was without effect. These data suggest that the
      failure of i.th. morphine to produce antiallodynic effects may be due, in part,
      to the lack of available functional spinal opioid mu-receptors which may occur
      following nerve injury. In contrast, the antiallodynic actions of i.p. or i.c.v.
      morphine appear to depend on supraspinal activation of opioid (mu?) receptors and
      subsequent activation of descending modulatory systems. The inconsistent data
      seen clinically with morphine in neuropathic pains may be related to the lack of
      supraspinal/spinal synergy that is normally associated with morphine efficacy in
      conditions of acute pain.

PMID- 8580423
TI  - Two actin binding proteins, actin depolymerizing factor and cofilin, are
      associated with Hirano bodies.
AB  - Hirano bodies are intracellular, paracrystalline, rod-like structures which
      contain actin, tropomyosin, vinculin, alpha-actinin, amyloid beta-protein
      precursor and several microtubule associated proteins (MAPs). These bodies are
      observed more frequently in the elderly and in a number of neurodegenerative
      diseases including Alzheimer's disease. Many of the proteins known to be
      associated with Hirano bodies are actin binding proteins. We present
      immunohistological evidence that actin depolymerizing factor (ADF) and cofilin,
      two closely related proteins that bind and sever actin filaments, are also
      components of Hirano bodies. However, we could detect no difference in the levels
      of expression of either ADF or cofilin in the hippocampal tissue from normal
      individuals and Alzheimer's disease patients.

PMID- 8580424
TI  - Induction of c-fos mRNA in the arcuate nucleus of normal and mutant growth
      hormone-deficient mice by a synthetic non-peptidyl growth hormone secretagogue.
AB  - We have studied by in situ hybridization histochemistry the mRNA expression of
      the c-fos immediate early gene in the brains of wild type and dwarf(dw/dw) and
      little(lit/lit) mutant mice after systemic injections of the synthetic GH
      secretagogues GHRP-6 and L-163,191. Both GH secretagogues induced a marked c-fos
      mRNA expression in the arcuate-ventromedial hypothalamus (ARC-VMH) of both
      control and mutant mice indicating a possible action on growth hormone releasing
      hormone (GHRH) neurones in the ARC-VMH. Both dw/dw and lit/lit mice showed a 5
      fold elevation in GHRH mRNA expression in the ARC-VMH compared with control
      animals under basal conditions. Since lit/lit mice have a reduced ability to
      secrete GH and lack a functional GHRH receptor while dw/dw mice lack both GH and
      presumably GHRH receptors, the GH-secretagogue-induced c-fos mRNA in the brain of
      these mutants are unlikely to be mediated by an indirect action of GH or a
      interaction of the synthetic GH-secretagogue with the GHRH receptor.

PMID- 8580425
TI  - PDGF-alpha receptor is expressed by mature neurones of the central nervous
      system.
AB  - The platelet-derived growth factors (PDGF) are constitutively expressed by
      neurones in the central nervous system (CNS). The synthesis of the PDGF-alpha
      receptor (PDGF-alpha R) is commonly attributed to oligodendrocyte precursors
      during late embryonic and early postnatal development, suggesting communication
      between neurones and glia which orchestrates amplification and final targeting of
      the myelinating cells. However PDGF A production persists when central
      myelination is achieved, which suggests that PDGF-alpha R are present in the
      adult CNS. In this study, we demonstrate the production of PDGF-alpha R
      transcripts and protein by various neuronal populations of the adult CNS. We
      propose a developmental shift, where glial cells and neurones are consecutive
      targets of PDGF A and neuromodulatory effects of PDGF, exerted on mature neurones
      via the expression of the PDGF-alpha R.

PMID- 8580426
TI  - Expression of mRNAs for neurotrophins and their receptors in the rat choroid
      plexus and dura mater.
AB  - The presence of the neurotrophin, nerve growth factor, brain derived neurotrophic
      factor, neurotrophin-3 and neurotrophin-4 (NGF, BDNF, NT-3 and NT-4) and their
      receptors of the tyrosine kinase family (trkA, trkB and trkC) have been
      investigated in the choroid plexus and dura mater of the adult rat by
      ribonuclease protection assay. The choroid plexus contained high levels of mRNAs
      for NGF and NT-4, and low levels of NT-3 and BDNF mRNA; and high levels of trkB
      mRNA, and undetectable levels of trkA and trkC mRNA. In the dura mater there were
      high levels of NT-3 and NGF, and low levels of BDNF and NT-4 mRNAs; and high
      levels of trkC mRNA, and relatively high amount of trkB mRNA, while levels of
      trkA mRNA was undetectable. The present analysis revealed a different
      distribution of neurotrophins and their related receptors in the choroid plexus
      and dura mater.

PMID- 8580427
TI  - Paramyotonia congenita without paralysis on exposure to cold: a novel mutation in
      the SCN4A gene (Val1293Ile).
AB  - The autosomal dominantly inherited phenotype of paramyotonia congenita (PC)
      without paralysis on exposure to cold MIM 168350) was originally described by De
      Jong in 1955. This phenotype is clearly different from classical paramyotonia
      congenita Eulenburg, which has been shown to be a sodium channelopathy resulting
      from mutations in the gene for the alpha-subunit of the human skeletal muscle
      sodium channel gene (SCN4A). From the clinical picture it has always been assumed
      that PC without paralysis to cold and PC Eulenburg are allelic disorders. In this
      study we present three German families with PC without cold paralysis, provide
      evidence that the disorder is linked to the SCN4A gene and report a novel SCN4A
      mutation (Val1293Ile) segregating in these families.

PMID- 8580428
TI  - S-100 beta immunoreactivity in neurones of the rat peripheral sensory ganglia.
AB  - S-100 beta, which is capable of exerting neurotrophic effects on cultured
      neurones and promoting the survival of motor neurones in vivo, has recently been
      found in distinct neurones of the rat hindbrain. Here we report that S-100 beta,
      as well as being present in satellite and Schwann cells, is also present in
      neurones of sensory ganglia (dorsal root ganglion, trigeminal, petrosal, jugular
      and nodose ganglia) but absent from neurones of the superior cervical ganglion.
      In the sensory ganglia, many neurones were immunoreactive, while the staining
      intensity varied among the neurones. Neuronal S-100 beta appeared in developing
      rats as early as postnatal day 1. No immunoreactive neurones were observed in the
      superior cervical ganglion during development. The results are suggestive of
      selective neurotrophic effects of S-100 beta.

PMID- 8580429
TI  - GM1 ganglioside inhibits ischemic release of amino acid neurotransmitters from
      rat cortex.
AB  - The effects of a 20 min period of four-vessel occlusion cerebral ischemia
      followed by reperfusion on glutamate, aspartate, GABA and glycine efflux from the
      rat cerebral cortex were studied using a cortical cup technique. Cerebral
      ischemia increased amino acid concentrations in the cortical superfusates. When
      the cerebral cortices were exposed to topically applied GM1 ganglioside (50
      microM) for 40 min prior to ischemia, the evoked efflux of all four amino acids
      was significantly inhibited. GM1 (1 microM) failed to inhibit amino acid release.
      The results support the concept that gangliosides have a cerebroprotective
      action.

PMID- 8580430
TI  - Ontogeny of two different benzodiazepine binding sites in the chick optic lobe.
AB  - The developmental time-course of type I and type II benzodiazepine receptors in
      the chick optic lobe was determined using a triazolopyridazine, CL 218872. At
      embryonic day 13 most of the binding sites corresponded to type II (98.23%),
      while type I represented only a minor proportion (1.77%). During development
      there was an increase in type I binding sites which reached 62.88% in adulthood,
      while type II binding sites decreased to 37.12%. These results demonstrate a
      differential ontogeny of two benzodiazepine receptor subtypes. Changes in the
      benzodiazepine binding population may account for the variability in the GABA
      benzodiazepine receptor interaction during chick optic lobe development.

PMID- 8580431
TI  - Assessment of striatal graft viability in the rat in vivo using a small diameter
      PET scanner.
AB  - A small diameter positron emission tomography (PET) scanner has been used to
      monitor [11C]raclopride (D2 receptor) binding in vivo in either intact striatum,
      denervated striatum following an excitotoxic lesion with ibotenic acid, or
      lesioned and grafted striatum following implantation of cortical or striatal
      tissue grafts in rats. Binding of [11C]raclopride was localized in the intact
      striatum within 20 min of injection of the radioligand, and was much reduced
      within the lesioned striatum. Cortical grafts exhibited a similar low level of
      binding to the lesioned striatum, whereas striatal grafts showed specific binding
      at an intermediate level. The [11C]raclopride binding signal in vivo correlated
      well with the extent of surviving or grafted striatal tissue observed post morten
      by Nissl staining and acetylcholinesterase histochemistry. Thus, the distribution
      of dopamine receptors as seen in the PET scanner are consistent with post mortem
      anatomical observations of striatal, lesion and graft sizes, and suggest that PET
      can provide a useful tool for monitoring the viability of implanted striatal
      graft tissues in vivo.

PMID- 8580432
TI  - Peripheral nerve repair: role of agarose matrix density on functional recovery.
AB  - This study presents quantitative data on the functional reinnervation of sweat
      glands, muscle and skin in the mouse paw after resection of the sciatic nerve and
      repair by entubulation with silicone tubes prefilled with agarose gels of
      different concentrations. The rate and the degree of functional recovery of
      animals with chambers filled with 0.5% agarose gels were slightly higher than
      with 1% agarose, and significantly higher than with 2% agarose. All these three
      groups recovered significantly better than a fourth group with an unrepaired
      resection. We conclude that peripheral nerves can regenerate through agarose gels
      in vvio and reinnervate distal target organs, but the concentration and the
      density of the exogenous intratubular matrix are important factors in determining
      the success of nerve regeneration and reinnervation.

PMID- 8580433
TI  - Methionine sulfoximine increases acetylcholine level in the rat brain: no
      relation with epileptogenesis.
AB  - Methionine sulfoximine induces epileptiform convulsions in rats. A possible
      involvement of acetylcholine in the onset of convulsions was investigated. A
      subconvulsive dose of methionine sulfoximine increased the brain acetylcholine
      concentration. After administration of a convulsive dose, atropine neither
      prevented the onset of the seizures nor prevented the increase in acetylcholine
      concentration. Physostigmine enhanced the increase in acetylcholine level but did
      not modify the time course nor the intensity of the convulsions. L-DOPA
      suppressed the seizures without inhibiting the increase in acetylcholine level.
      The choline content decreased after the convulsant dose. The increase in
      acetylcholine content is therefore not the unique cause of the seizures, which
      could result from the reduction of striatal inhibition due to a decrease in
      dopamine level induced by methionine sulfoximine.

PMID- 8580434
TI  - Facilitation of N-methyl-D-aspartate-evoked acetylcholine release by hydroxyl
      radical scavengers.
AB  - Effects of hydroxyl radical scavengers such as dimethylthiourea (DMTU), uric acid
      and mannitol on acetylcholine (ACh) release evoked by N-methyl-D-aspartate (NMDA)
      were examined in cerebral cortical neurones. NMDA increased dose-dependently ACh
      release. This increase in the release was significantly suppressed by MK-801, N
      omega-nitro-L-arginine and haemoglobin, indicating that NMDA evokes ACh release
      via the formation of NO subsequent to NMDA receptor activation. DMTU dose
      dependently enhanced the NMDA-induced ACh release. Uric acid (100 microM) and
      mannitol (1 mM) facilitated significantly the NMDA-induced ACh release, although
      these scavengers themselves showed no effects on ACh release in the absence of
      NMDA. These results indicate that the removal of hydroxyl radical facilitates the
      NO-induced ACh release.

PMID- 8580435
TI  - Hyaluronectin binds to laminin and blocks laminin-dependent process formation by
      astrocytes.
AB  - The interaction of hyaluronectin (HN), a hyaluronic acid-binding extracellular
      matrix (ECM) glycoprotein with two other ECM-associated molecules, laminin and
      fibronectin, was studied by ligand blot and solid phase ligand binding assays.
      Ligand blot analysis with biotin-labeled HN revealed a strong binding of HN to
      immobilized laminin and a weaker binding to fibronectin. Ligand binding studies
      indicated a concentration dependent, Ca(2+)-independent binding of HN to laminin.
      Binding of HN to laminin but not to fibronectin was resistant to increased salt
      concentrations indicating a non-electrostatic, protein-protein interaction of HN
      with laminin. The functional relevance of HN-laminin interaction was demonstrated
      by an inhibition of laminin-supported astroglial process formation by HN.

PMID- 8580436
TI  - Characterization of an Na(+)-dependent glutamate/aspartate transporter from
      cultured Bergmann glia.
AB  - The properties of a transport system specific for L-glutamate and L-aspartate
      activity expressed in Bergmann glia cells from chick cerebellum were examined.
      The uptake of D-[3H]aspartate was inhibited by the endogenous substrates L
      aspartate (Ki = 62 microM) and L-glutamate (Ki = 60 microM). Of the identified
      uptake inhibitors, L-aspartate-beta-hydroxamate (Ki = 900 microM), L-alpha
      aminoadipate (Ki = 2000 microM), 4,4'diisothiocyanatos-tilbene-2,2'-disulphonic
      acid (DIDS) (Ki = 1000 microM) and 4-acetamido-4'-isothiocyanatostilbene-2,2'
      disulphonic acid (SITS) (Ki = 100 microM) inhibited D-[3H]aspartate uptake.
      Northern blot analysis, revealed the expression of a chick homologue of a the rat
      brain L-glutamate/L-aspartate transporter (GLAST). These data suggest that GLAST
      may be involved in the regulation of the parallel fibre-Purkinje cell synapse
      ensheathed by Bergmann glia.

PMID- 8580437
TI  - Spermine mediates inward rectification of Ca(2+)-permeable AMPA receptor
      channels.
AB  - AMPA-gated glutamate receptors with an inwardly rectifying current-voltage (I-V)
      relationship and substantial Ca2+ permeability are expressed in a population of
      cultured rat hippocampal neurones (type II neurones). The inward rectification of
      these AMPA receptors was gradually lost in cell-free membrane patches. The I-V
      relationship of the AMPA receptors displayed a slight outward rectification in
      most patches 10 min after excision. This loss of inward rectification was not
      accompanied by a change in the Ca2+ permeability. The inward rectification was
      maintained by applying physiological concentrations of spermine to the
      cytoplasmic side of patch membranes. These results indicate that some cytoplasmic
      factor mediates inward rectification in the Ca(2+)-permeable AMPA receptors, and
      that a candidate for this substance is spermine.

PMID- 8580438
TI  - The effects of bilateral striatal lesions on the acquisition of an operant test
      of short term memory.
AB  - It has been previously shown that lesions of the dorsal striatum can disrupt
      performance on a variety of cognitive tasks related to frontal cortex function.
      In order to extend these studies, we have investigated the effects of bilateral
      striatal lesions on the acquisition of an operant test of short term memory in
      the delayed non-matching to position paradigm. The animals received either
      ibotenic acid or saline control injections into the dorsal striatum prior to
      training on the non-matching task. Striatal lesions retarded acquisition of the
      task, although with further training the lesioned rats achieved a similar level
      of asymptotic performance to the control animals. The lesioned rats also
      exhibited marked nocturnal locomotor hyperactivity when tested under conditions
      of food deprivation, but not when tested satiated. The results indicate that
      bilateral striatal lesions induce mild deficits in the acquisition of the
      discrimination rules involved in performance of the delayed non-matching to
      position task. The present study does not support a role for the neostriatum in
      the specific mediation of short term memory in a operant DNMTP test.

PMID- 8580439
TI  - Region-specific effects of ovarian hormones on estrogen receptor
      immunoreactivity.
AB  - The cell groups in which nuclear estrogen receptor (ER) expressing neurons are
      found have unique, often coordinated, functions. Regulation of ER content may be
      one mechanism through which feedback responses can be adjusted to match the
      function of a specific brain region and physiological circumstance. In these
      immunocytochemical experiments, estrogen decreased staining intensity for ER in
      the ventrolateral hypothalamus and bed nucleus of the stria terminalis, but not
      in the periventricular preoptic area. ER staining intensity was further decreased
      by progesterone, following estrogen, but not in all brain regions. These results
      suggest that ER is regulated by estrogen in a region-specific manner.
      Furthermore, inhibition of responses to estrogen by progesterone may involve
      progesterone-induced down-regulation of ERs.

PMID- 8580440
TI  - Spectral responses in the gamma-band: physiological signs of higher cognitive
      processes?
AB  - It has recently been proposed that brain responses in the gamma-range (> 20 Hz)
      include information about specific cognitive processes in the human brain.
      Empirical data substantiating this assumption come from EEG and MEG recordings
      during visual and language processing. For example, 30 Hz activity has been found
      to be stronger during processing of words than during processing of meaningless
      but pronounceable pseudo-words. However, it has been reported that power changes
      in the gamma-band are sometimes artefacts of changes taking place in other
      frequencies, such as the alpha-band. In this study, we investigated power changes
      in frequency bands outside the gamma-range and found no evidence that such
      changes are related to the dynamics in gamma-power distinguishing between words
      and pseudowords. These results are consistent with the view that gamma-band
      responses are an indicator of lexical processing and other cognitive processes
      related to binding of stimulus features into a whole (Gestalt), as proposed by
      Singer.

PMID- 8580441
TI  - Different functions of rat's pedunculopontine tegmental nucleus are reflected in
      cortical EEG.
AB  - Previous investigations suggest a crucial role of the pedunculopontine tegmental
      nucleus (PPTg) in elicitation of cortical EEG alterations during paradoxical
      sleep. In order to reveal a participation of this nucleus in the regulation of
      the cortical EEG also during waking states and slow wave sleep unilateral
      ibotenic acid lesions of this nucleus were made in 12 Long-Evans rats. The lesion
      induced alterations of the frontal and occipital EEG were determined by FFT
      spectral power analysis. The lesion caused ipsilaterally a suppression of the
      hippocampal theta rhythm recorded on the occipital cortex during exploratory
      sniffing. During head washing the frontal delta waves were found to be elevated
      ipsilaterally. Suppressions of the slow sleep waves were found in the
      contralateral occipital as well as in the frontal EEG. The results indicate
      involvements of the PPTg in the regulation of the hippocampal and of the motor
      activity in waking states as well as in the regulation of the sleep delta waves.

PMID- 8580442
TI  - Phorbol ester alters rat hippocampal neuronal response to hypoxia.
AB  - The effect of the protein kinase C (PKC) activator, 4 beta-phorbol-12, 13
      dibutyrate (beta-PDBu) on electrophysiological properties of rat hippocampal CA1
      neurons exposed to moderate hypoxia was examined. Hypoxic beta-PDBu-pretreated
      neurons differed from untreated neurons by exhibiting an adenosine-independent
      loss of synaptic transmission, an apparent large increase in injected threshold
      current necessary to elicit an action potential, an increase rather than a
      decrease in membrane resistance, and an increase rather than a decrease in
      hyperpolarizing holding current. Additional experiments with an adenosine A1
      antagonist suggest that beta-PDBu alters neuronal responses to hypoxia through
      some mechanism other than the documented ability of beta-PDBu to uncouple the A1
      receptor.

PMID- 8580443
TI  - Co-localization of NOS and NMDA receptor in esophageal premotor neurons of the
      rat.
AB  - Nitric oxide (NO) production following NMDA receptor stimulation plays a role in
      signaling between neurons. Using trans-synaptic tracing with pseudorabies virus
      (PRV), immunocytochemistry and histochemistry, we have demonstrated the
      expression of NMDAR1 and nitric oxide synthase (NOS) within brain stem neurons
      controlling esophageal peristalsis. PRV-immunoreactive second order esophageal
      premotor neurons of the central subnucleus of the nucleus of the solitary
      (NTScen) expressed NMDAR1 and NOS. First order motoneurons of the compact
      formation of the nucleus ambiguus (NAc) expressed NMDAR1, but did not contain
      NOS. NTScen neurons may synthesize and release NO in response to NMDA activation,
      suggesting a role for NO in the coordination of esophageal motility.

PMID- 8580444
TI  - Localization of vinculin and talin at perineurial cells of human sural nerve.
AB  - Immunolocalization of spectrin, vinculin, talin, desmin and titin was
      investigated in human sural nerve. No binding for spectrin and titin was seen in
      any structure of the nerve. Antibody against desmin immunostained sporadic
      epineurial vessels only. Endoneurial and epineurial vessels were intensely
      positive for vinculin and talin. We found expression of vinculin and talin at the
      perineurial cells, using immunocytochemistry and gold immunoelectron microscopy.
      Since vinculin and talin are known to be involved in cell-cell and cell
      extracellular matrix transmembrane connections, we propose that they, possibly
      together with other cytoskeletal proteins, may be implicated in the permeability
      barrier property of the perineurium. In pathological conditions, perineurium
      plays an as yet unknown role. Future studies are needed to investigate expression
      of vinculin and talin in neuropathies.

PMID- 8580445
TI  - Cholecystokinin enhances the acoustic startle response in rats.
AB  - The present study examined the effects of the neuropeptide cholecystokinin (CCK)
      on neurones of the caudal pontine reticular nucleus (PnC), which mediates the
      acoustic startle response (ASR) in rats. Electrophysiological experiments
      revealed an excitatory effect of CCK on acoustically responsive neurones in the
      PnC. On the behavioural level, CCK also enhanced the ASR. Since the PnC is not
      only an obligatory relay station of the brain circuit mediating the ASR, but also
      receives modulatory input from brain areas involved in the expression of fear and
      anxiety, the enhancement of the ASR by CCK could be interpreted as an anxiogenic
      like effect of this peptide.

PMID- 8580446
TI  - Non-reciprocal control of rhythmic activity in respiratory-modulated XII
      motoneurons.
AB  - To elucidate the nature of phasic respiratory inputs to hypoglossal (XII)
      motoneurons, we assessed the phasic changes in membrane resistance (RN) in
      inspiratory- and expiratory-modulated motoneurons. In expiratory motoneurons, RN
      was consistently lower in inspiration than in expiration and intracellular
      injection of negative current reversed the phasic hyperpolarizing membrane
      potential wave in inspiration. In inspiratory motoneurons, RN changed less but
      also was minimal in inspiration. In these neurons, injection of a negative
      current sufficient to reverse a lingual nerve-evoked IPSP did not reverse the
      phasic expiratory hyperpolarization. Thus, respiratory-related inhibitory inputs
      are non-reciprocal in inspiratory and expiratory XII motoneurons, with
      inspiratory motoneurons probably lacking a somatic, amino acid-mediated
      inhibitory input in expiration.

PMID- 8580447
TI  - Micrographia in Parkinson's disease.
AB  - A computational neural model of movement production in normal and Parkinson's
      disease (PD) is used to provide a neural account for the source of micrographia
      in PD handwriting. It is hypothesized that smaller than normal pallido-thalamic
      signals, due to dopamine depletion, are responsible for the observed overall
      smallness, slowness and variability in PD handwriting. Experimental data from PD
      patients that show micrographia support this hypothesis and imply the functional
      segregation of basal ganglia neural populations.

PMID- 8580448
TI  - Evidence for local synthesis of melatonin in golden hamster retina.
AB  - Daily variations in melatonin content of retinas of pinealectomized and sham
      operated golden hamsters were studied. Melatonin content showed significant daily
      variations with maximal values at night (i.e. early in the night in
      pinealectomized hamsters and late at night in sham-operated animals). Moreover,
      mean retinal melatonin levels augmented significantly after pinealectomy. In
      vitro the augmented melatonin levels found in retinas incubated in darkness for 8
      h was suppressed by exposure to light, indicating the ability of hamster retina
      to regulate melatonin synthesis in isolated conditions. Taken together, the in
      vivo and in vitro results support daily variations of melatonin content of
      exclusive retinal origin.

PMID- 8580449
TI  - [Pilot program of immunization against viral hepatitis B, integrated in the
      extended immunization program in Abancay (peru)].
AB  - INTRODUCTION: Abancay is located at 2,395 m.a.s.l. in the Peruvian Andean Region.
      It is a hyperendemic area for Hepatitis B virus (HBV) and hepatitis delta virus
      (HDV) infection, where 7% of the deaths are caused by acute and chronic hepatitis
      infections. In 1991, a pilot immunization program against HBV infection was
      started to control the incidence of VHB-VHD, and as a strategy to improve the EPI
      coverage in general. METHODS: Vaccination population was programmed to include
      1,301 children under 1 year old and 3,488 children between 1-4 years old. A total
      of 3 doses of DNA recombinant vaccine against HBV per child were administered.
      The vaccination schedule fit within the EPI immunization schedule. For children
      under one year old, the program includes: Newborn: BCG, Polio 1, HBV1; 2-month
      old: Polio 2, DPT1, HBV2; 3-month old: DPT2, Polio 3; 4-month old: polio 4, HBV 3
      and; 9 month old: Measles. For children aged between 1 and 4 years old, the
      program includes: HBV1, HBV2 one month after HBV1, and HBV six months after HBV1.
      RESULTS: One year after the immunization program started, 1,262 (97.0%) children
      under one year old and 2,529 (72.5%) between 1-4 years old were immunized. No
      relevant adverse effects have been reported. There were 8 deaths due to acute
      respiratory infection and acute diarrhea diseases, which are the main causes of
      death in this area. One of the objectives achieved was an improvement in the EPI
      vaccination coverage for children younger than 1 year old, with a DPT coverage of
      97.0% in 1991 compared to 63.0% in 1988, 26.9% in 1989, and 61.9% in 1990.
      CONCLUSION: The inclusion of HVB vaccination in the EPI for a HBV and HDV endemic
      area improves the total EPI coverage and it is safe an effective.

PMID- 8580450
TI  - [Adenoma of the colon and rectum].
AB  - 318 adenomatous polyps were removed by colonoscopic polypectomy, from two hundred
      patients, between 25 to 88 years old; 60.50% men, and 39.50% women. 86.50% of
      patients were older than 50 years old. In 64.50% of patients the adenomatous
      polyp was single, and 35.50% had "multiple adenoma"; the lesions distribution was
      72.64% in the rectum-sigmoid colon. The grade of dysplasia was severe in adenomas
      over 20mm, and in those of villous type. The malignant percentage was: 1.61% in
      the adenomatous polyp under 10mm in diameter, 8.49% in those of 10mm to 19mm, and
      30.68% in the adenomas of 20mm or more. The adenocarcinomatous focus increased
      from 1.69% in the adenomas under 10mm to 58.33% in those of 40mm or more in
      diameter. The relationship between type of adenomatous polyp and his
      adenocarcinoma incidence was 7.66% in tubular type, 22.22% in tubular-villous,
      and 26.32% in villous type. The carcinoma incidence in all of the adenomas of
      this series was 11.95%.

PMID- 8580451
TI  - [Risk factors for persistent diarrhea].
AB  - The current concepts in persistent diarrhoea (PD) are reviewed. 102 patients with
      acute diarrhoea and 85 with PD are studied. All were less than one year old.
      Information about age, nutritional status, time of breast feeding, previous
      episodes of acute and persistent diarrhoea and the previous use of drugs is
      registered. Microbiological and parasitologics studies were done to identify
      enteric pathogens. To prove the association of PD and the exposure to different
      risk factors the statistic method of Chi square (chi 2) was used and the odds
      ratio (OR) estimated. In order of importance and according to the OR the risk
      factors identified were: previous episodes of PD, malnutrition, less than one
      month with breast feeding, the use of metronidazol and antibiotics, multiple
      infections, previous episodes of acute diarrhoea and the identification of
      enteric pathogens. The most frequent pathogen was Salmonella followed by entero
      pathogenic Escherichia coli.

PMID- 8580452
TI  - [Histologic types of gastric cancer according to the Lauren classification at the
      Cayetano Heredia National Hospital].
AB  - The histological samples of stomach with gastric cancer diagnosis were evaluated
      and classified according to Lauren's criteria. The samples were obtained of 148
      patients attended at the Hospital Nacional Cayetano Heredia, Lima, Peru, between
      January 1988 and December 1995. According to this classification 99 patients
      (67%) were from the intestinal type and 40 (27%) from the diffuse type. A group
      of nine patients (6%) was considered as mixed and unclassified. The diffuse type
      was more frequent in females and the intestinal type for males. We demonstrated
      with statistical validity that the diffuse type is more frequent in the youngest
      and the intestinal type in the oldest. In this study there was no significative
      statistical difference for the localization according the histologic type.
      However in the three groups the simultaneous involvement of two gastric regions
      is very frequent, mainly in pyloric antrum and body of the stomach.

PMID- 8580453
TI  - [Clinical characteristics of Meckel's diverticulum in a population of children].
AB  - A descriptive and retrospective study was realized during a period of eleven
      years from January 1983 to December 1993. There were found 101 cases, of which
      75.25% were Meckel's diverticulum complicated. The incidence found was of 1.2%.
      The 89.5% of the complicated cases were less than 10 years old, and the 47.4%
      were less than 2 years old. The most frequent symptoms were: abdominal pain
      (68.4%), vomiting (68.4%), fever (47.3%), and abdominal distention (39.4%). The
      congenital anomalies presented in 17.8%, were: intestinal malrotation, congenital
      bands, hernia inguinal and omphalocele. The most common complications were:
      intestinal obstruction (47.4%), diverticulitis (19.7%), lower digestive
      hemorrhage (15.8%), and intestinal perforation (14.5%) of the cases. The
      heterotopic tissue was present in 20.7% cases. In our Institute, the age's group
      less than 2 years old, presented more complicated cases (p < 0.01). The
      intestinal obstruction was the most common picture (p < 0.001). The lower
      gastrointestinal hemorrhage was the second complication in patients less than 2
      years old (p < 0.05). We found a strong association with other congenital
      anomalies.

PMID- 8580454
TI  - [Early gastric cancer].
AB  - Younger than 40 years old reached a 27.5% and the group of older than 40 years
      old reached a 72.5%. The predominant sex was the female that reached a 65%.
      Ulcerated and depressed lesions reached to 70%. The clinical symtomatology
      referred was ulcerous syndrome in 42.5% and non-characteristic epigastralgy in
      35% with symptoms which last less than 6 months or between 6 and 12 months or
      between 1 and 2 years near 30% in each one of the groups. In 25% of the patients,
      radiological and/or endoscopic diagnosis of peptic ulcer was found that have
      obtained alleviation with antitulcerous treatment.

PMID- 8580455
TI  - [Resectable stomach cancer: analysis of 134 consecutive cases].
AB  - An analysis was made on 134 patients with gastric cancer underwent conventional
      gastrectomy consecutively at Belen Hospital, Trujillo, Peru from 1966 to 1990.
      The main objective was to determine the influence on prognosis of independent
      treatment variables and treatment-dependent variables. Gastric cancer patients
      (78M:56F) had a median age of 58 years (range, 23 to 82 years). The resectability
      rate was 48%. The operative mortality rate was of 14.2%. The 5-year actuarial
      survival rate of this series was 16% (33% for curative gastrectomy and 1% for
      palliative gastrectomy, p < 0.001). Using univariate analysis, the evolution of
      gastric cancer was related to palpable mass, macroscopic appearance, tumor size,
      depth of invasion, tumor stage, lymph node involvement, distant metastases,
      number of lymph node metastases and operative curability, parameters that
      affected the rate of survival. However the most important prognostic factor was
      curability, and almost all patients who survived more than five years were among
      those submitted to curative gastric resection. The clinical course was not
      related to age, gender, length of history, location of tumor, histologic type and
      operative procedure. We concluded that the feasibility of a curative resection
      would be increased and the prognosis probably improved if the carcinoma could be
      detected at an early stage.

PMID- 8580456
TI  - [Peptic ulcer: late complications of the surgical treatment].
AB  - The incidence of surgical treatment of peptic ulcer decreased in the last two
      decades. The majority of procedures for surgical management of peptic disease
      impairs the ability of the stomach to receive and to store food. The intake of
      high protein-caloric content diets can improve some nutritional deficits
      expressed by loss of body weight and anemia. The mechanism responsible for
      diarrhea is unknown, but truncal vagotomy has the highest incidence. It is
      usually episodic, lessens over the first year after operation and rarely remains
      a severe problem. The decreasing levels of colecistokinin response after meal in
      gastrectomy and the division of hepatic branch of anterior vagus can cause
      gallbladder sludge and stone formation. Alkaline reflux explains gastritis and
      esophagitis after partial gastric resection. Surgical duodenal diversion, like a
      Roux-en-Y limb, have been successful in its control. The mechanism that leads to
      the dumping syndrome are loss of gastric reservoir function and rapid emptying of
      hyperosmolar meals into small intestine. Somatostatin analogues improve the
      symptoms caused by abnormal release of neurohormonal agents responsible of the
      behaviour of the gastrointestinal tract after meals. Cancer of gastric remanent
      may be due to increased bacterial overgrowth and nitrosation formation. The
      endoscopic follow-up is essential for early diagnosis of the stump cancer. In
      spite of all complications, the surgeon cannot have hesitations by carrying out
      radical approach meanly during catastrophic emergencies of peptic disease i.e. in
      elderly aged patients. Nowadays, the control of chronic sequelas is easy with
      conservative therapeutic.

PMID- 8580457
TI  - [Ulcerative colitis: medical treatment].
AB  - Ulcerative colitis is a chronic inflammatory disease of unknown etiology,
      affecting the mucosa of the rectum and a variable length of colon. There is no
      medical cure for this disease, however medical therapy offers comfort to the
      majority of patients and improves their lives. Medical therapy including newer
      drugs is here reviewed.

PMID- 8580458
TI  - [Strongyloides stercoralis hyperinfection syndrome in a patient with human
      immunodeficiency virus (HIV) infection: report of a case and review of the
      literature].
AB  - A case of a twenty-one year old woman with Strongyloides stercoralis
      hyperinfection associated with human immunodeficiency virus infection that
      represents the fifteen case reported in the literature is here presented.
      Hypothesis for which this association is infrequent and several therapeutic
      alternatives are reviewed.

PMID- 8580459
TI  - [Gastric cancer in children: report of a case].
AB  - Gastric cancer is rare in children. The case of a 5-year-old girl advanced well
      differentiated tubular adenocarcinoma of the gastric cardia and abdominal
      carcinomatosis is described. This child is the youngest patient with cancer of
      the stomach reported in our population.

PMID- 8580460
TI  - [Hepatic veno-occlusive disease associated with ingestion of Senecio
      tephrosioides].
AB  - A case of hepatic veno-occlusive disease (HVOD) in a 38 year-old woman is
      reported. She had occasionally consumed "Huamanrripa" (Senecio tephrosioides) as
      a cough remedy for many years. She was hospitalized because she had presented
      abdominal pain, jaundice and anasarca during 10 weeks. The histological studies
      of hepatic biopsy showed pronounced congestion to centrilobulillar predominance,
      focus of necrosis and a reversed lobulation pattern in some areas. In the next 13
      months she was hospitalized four times due to complications of portal
      hypertension. This is the first reported case of HVOD associated with S
      tephrosioides ingestion. It is very probable that this plant used in peruvian
      traditional medicine contains pyrrolizidine alkaloids, hepatic and nephrotoxic
      substances that are present in other species of Senecio genus. Due to present
      popularity of alternative medicine, an increment in HVOD incidence is expected.

PMID- 8580462
TI  - Development of TCR gamma delta iIELs.
AB  - Interest has focused recently on the development and function of T and B
      lymphocytes in the mucosal surface, particularly on a population of intestinal
      intraepithelial lymphocytes (iIELs) that develop by thymic and extrathymic
      pathways in the mucosa (for review see ref 1). Our approach to studying TCR gamma
      delta iIEL development has been to utilize G8 transgenic (Tg) mice expressing an
      antigen-specific, developmentally-regulated, gamma delta TCR. These mice have
      provided a useful tool to dissect T-cell development of intestinal TCR gamma
      delta cells. In this review, we summarize our findings of studies using this
      model system to dissect the complex events that regulate TCR gamma delta iIEL
      development and functional activity. The data suggest a maturational scheme for
      TCR gamma delta iIELs wherein the majority of TCR gamma delta iIELs migrate to
      the gut in an immature state where they develop in response to TCR ligation. As
      TCR gamma delta iIELs develop, surface and functional phenotypes change in a
      discernable pattern. These findings provide an important first step in analysing
      TCR gamma delta development, maturation and differentiation in normal animals.

PMID- 8580461
TI  - T-lymphopoietic capacity of the mouse intestinal epithelium.
AB  - Small intestine intraepithelial lymphocytes (i-IELs) comprise a heterogeneous
      population of T cells that are part of the gut-associated lymphoid tissues.
      Recent studies indicate that murine i-IELs are greatly enriched for extrathymic T
      cells. Yet there is disagreement as to which i-IELS are extrathymic and which are
      not, and many aspects of intestinal T-cell development remain controversial. In
      this article, the developmental lineages of murine i-IELs are examined, and the
      thymopoietic potential of the intestine epithelium is discussed. A mechanism is
      described whereby all intestinal T cells develop extrathymically, and a concept
      of intestinal T cells is presented which suggests that lineages of i-IELs need to
      be viewed according to developmental factors exclusive of thymus dependency.

PMID- 8580463
TI  - The TCR-beta chain repertoire of gut-derived T lymphocytes.
AB  - The gastrointestinal tract represents a natural barrier to environmental
      pathogens. The gut-associated lymphoid tissue (GALT) provides protection and
      interacts with the external environment, e.g. bacteria and food antigens. Large
      numbers of leukocytes are present as aggregates in the lymphoid follicles and as
      single cells in the lamina propria and epithelium. Intraepithelial T lymphocytes
      are localized within the tight junctions between epithelial cells. In
      conventional adult mice, they mainly express CD8, with half of the cells
      expressing the common CD8 molecule, the CD8 alpha beta heterodimer and the other
      half expressing a homodimer CD8 alpha alpha. The CD8 alpha beta IEL bear a TcR
      alpha beta while CD8 alpha alpha bear either a TcR gamma delta or a TcR alpha
      beta. Studies of repertoire with human IEL cell lines and with total human IEL
      population showed that both the alpha-chain and the beta-chain repertories are
      oligoclonal. Our own results of the analysis of repertoire diversity in
      genetically identical mice raised the same environment have shown that both CD8
      alpha alpha and CD8 alpha beta TcR alpha beta IEL populations express a distinct
      oligoclonal repertoire that differs from one individual to the next. Compared to
      the lymph node lymphocytes, both IEL populations are composed of a very limited
      number of clones that undergo clonal expansion. Furthermore, the study of
      repertoire throughout the length of the small intestine has revealed that some of
      the clones are present all along the epithelium suggesting that the CD8 alpha
      alpha IEL and CD8 alpha beta IEL are capable of recirculating or migrating in the
      intestine. We propose that the repertoire of TcR alpha beta IEL is derived from a
      restricted number of T cells that either develop in situ or that arrive through
      circulation and can then undergo clonal expansion.

PMID- 8580464
TI  - T-cell development and selection in the intestinal epithelium.
AB  - Though it is now well established that T lymphocytes develop in the murine
      intestinal epithelium, many features of T lymphopoiesis occurring at this site
      remain controversial and poorly understood. One of the most contentious issues is
      whether all TcR alpha beta+ iIEL subsets, characterized by the differential
      expression of CD4, CD8 alpha and CD8 alpha, develop in situ, as suggested by the
      analysis of athymic radiation chimeras and parabionts. Athymic radiation chimeras
      have also been used to study positive and negative selection events imposed on
      developing iIEL expressing an MHC class I restricted transgenic TcR alpha beta.
      Results reveal that while distinct mechanisms may regulate these processes in the
      gut, the functional repertoire generated at this site is identical to that
      resulting from intra-thymic T-cell development. Strikingly, this is not the case
      for the development and selection of iIEL expressing an MHC class II restricted
      TcR alpha beta. Features peculiar to MHC class II molecules expressed by
      enterocytes are discussed in this context. In addition, two model systems are
      presented towards understanding the basis for the observed oligoclonal repertoire
      of TcR alpha beta+ iIEL. Specifically, the role of luminal antigen is addressed
      by comparing the repertoire of iIEL developing in the orthotopic gut with that of
      iIEL developing in an ectopic sterile intestine in the same athymic animal. The
      role of TcR alpha beta-mediated signals in support of the putative oligoclonal
      expansion of iIEL, is addressed using mice lacking the protein tyrosine kinase,
      Lck.

PMID- 8580465
TI  - The beta 7 integrins in mucosal homing and retention.
AB  - Lymphocytes recirculate extensively throughout the body and then localize in
      tissues and lymphoid organs. This is accomplished by an array of adhesion
      molecules on lymphocytes and counter-receptors on the vascular endothelium,
      extracellular matrix and the epithelium. Recent studies have identified several
      of the specific molecular interactions that mediate lymphocyte trafficking.
      Lymphocytes expressing alpha 4 beta 7 home to the intestine through recognition
      of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on Peyer's
      patch high endothelial venules. T cells in nearly all mucosal epithelial sites
      express the alpha E beta 7 integrin which has been shown to mediate lymphocyte
      binding to epithelial cell E-cadherin. Thus, members of the B7 subfamily of
      integrins, alpha E beta 7 and alpha 4 beta 7, and their counter-receptors, are
      believed to play key roles in directing lymphocyte traffic to and retention in
      mucosal organs.

PMID- 8580466
TI  - At risk, infected, and invisible: older gay men and HIV/AIDS.
AB  - Older gay men over the age of 50 have been and continue to be an invisible part
      of the HIV/AIDS epidemic. The reasons for this phenomenon are many, but among
      them are societal beliefs, myths, and stereotypes emanating from ageism and
      homophobia. In addition, HIV/AIDS is sometimes misdiagnosed in older adults
      because many of its symptoms mimic other illness that affect older people. Among
      the HIV risk factors of older gay men are internalized homophobia, denial of
      risk, alcohol and other substance use, and anonymous sexual encounters. The
      challenge for nurses and other providers is to reach, educate, and assist older
      gay men effectively in changing and maintaining safe behaviors when they are
      engaging in sexual and drug-using behaviors that can transmit HIV.

PMID- 8580467
TI  - Healthcare needs of HIV-infected persons in hospital, outpatient, home, and long
      term care settings.
AB  - In this descriptive study, healthcare needs reported by 386 HIV-infected persons
      from all risk categories and their primary nurses from four care settings
      (hospital, outpatient, long-term care, and home) are identified. Healthcare needs
      were classified into four domains of nursing practice using a conceptual
      framework from community health nursing--physiologic, psychosocial, health
      behaviors, environmental--and were assessed using the Healthcare Needs Scale for
      Patients with HIV/AIDS. Nurses' perceptions of major healthcare needs across all
      settings centered around decreased physical endurance, limited physical mobility,
      and sensory deficits. Patients' needs focused on financial issues. The results
      reflect the multidimensional nature of this infection and provide direction for
      clinical practice.

PMID- 8580468
TI  - AIDS nursing care and standardized nursing language: an application of the
      nursing intervention classification.
AB  - Standardized nursing language is recommended increasingly as a method to describe
      the work of nursing, adapt to computerized documentation, and establish a place
      for nursing in national data bases. Nursing diagnosis has become a standard label
      for assessment data. The Iowa Interventions Project Research Team proposes that
      Nursing Interventions Classification (NIC) be adopted to label nursing
      interventions. The author applies NIC to HIV/AIDS nursing care guidelines from
      the literature and concludes that NIC can be an important tool as HIV/AIDS nurses
      develop and describe their knowledge base.

PMID- 8580469
TI  - Health-illness beliefs and practices of Haitians with HIV disease living in
      Boston.
AB  - The authors of this qualitative study explored the health-illness beliefs and
      practices of Haitians with HIV disease. The authors obtained a purposive sample
      of five Haitian men and four Haitian women with symptomatic HIV disease or AIDS
      living in Boston. Five themes were identified through content analysis of
      interviews and medical record review: (a) incorporation of traditional health
      illness beliefs into beliefs about HIV disease; (b) A perceived need to hide HIV
      disease to avoid rejection, humiliation, and isolation; (c) use of spirituality
      to help cope with HIV disease; (d) history of limited contact with doctors prior
      to diagnosis of HIV disease; and (e) use of traditional healing practices for HIV
      disease. The findings have implications for improving cross-cultural
      communication between Haitians with HIV disease and their healthcare providers.

PMID- 8580470
TI  - Perceived barriers to getting published: results of the JANAC survey.
AB  - In order to identify strategies to promote the publication of ANAC members'
      knowledge and expertise, the authors conducted a survey of JANAC readers. Twenty
      four respondents, almost all clinicians, identified 25 areas of interest they
      want to develop for publication. Barriers to getting published fell into four
      categories: lack of time, writing skills, self-confidence, and motivation or
      ideas. Suggestions for facilitating scholarship focused mainly on collaboration
      with writing experts and learning through educational workshops. The results of
      this study can serve as a guide in the development of services to readers
      interested in their own development as scholars.

PMID- 8580471
TI  - Charles Turner Thackrah: a pioneer in the field of occupational health.

PMID- 8580472
TI  - Implementation of a quality system for the examination of occupational diseases.
AB  - A quality system in accordance with the principles of the ISO 9004-2 standard has
      been implemented at a department examining patients with occupational diseases.
      The quality system is the organizational structure needed to implement total
      quality management (TQM). The purpose of the system is to ensure that everyone is
      aware of the common quality objectives and knows how to achieve them. The quality
      system involves participation, training and guidelines and is based on customers'
      satisfaction and fluency of the activities. When the duration of the completed
      examinations was used as a measure of the fluency, this study demonstrated that
      TQM is feasible in health care. The fluency increased spontaneously due to
      increased awareness of rapidity as one of the quality characteristics and better
      understanding of the entire work process. This practical approach seems to be a
      good way to build up the basic quality and to motivate the personnel.

PMID- 8580473
TI  - A systematic approach to health surveillance in the workplace.
AB  - This paper reviews the range of health surveillance activities which can be
      utilized in the workplace by occupational health professionals for assessing
      fitness for work and contributing to the prevention of occupational illness and
      promotion of good health. The systematic approach described categorizes health
      surveillance procedures into occupational or non-occupational, risk-based or
      unfocused, and as primary, secondary or tertiary preventive measures. All
      categories of health surveillance are currently being practised to some extent,
      but the type of surveillance may not match the needs of the workplace in some
      situation. In order to aid health professionals in deciding which procedures
      should be implemented, recommendations based on an assessment of health risks are
      made. The key proposal is to establish a minimum level of periodic health
      surveillance for all workers based on a targeted lifestyle health risk assessment
      and a structured health questionnaire. Additional procedures can then be added
      sequentially as appropriate to manage any health risks in the workplace. The role
      of the unfocused periodic general medical examination is discussed in the context
      of the systematic approach and allows occupational professionals to critically
      appraise its usefulness.

PMID- 8580474
TI  - A study of migraine and its effects in a working population.
AB  - The objective of this study was to determine the prevalence of migraine and its
      impact in a working population. A random sample of 476 employees in a chemical
      industry research and commercial centre took part in this cross-sectional
      questionnaire-based study. The questionnaire assessed the past-year prevalence of
      migraine, frequency and duration of episodes, effect on work and sickness
      absence, use and efficacy of medication and possible 'trigger factors'. Migraine
      prevalence was 23.2% in women and 11.6% in men. Migraineurs reported
      significantly more headache-related sickness absence, but did not have
      significantly more recorded sickness absence overall than did non-migraineurs. Of
      the migraineurs, 42% had never sought medical advice regarding headaches and most
      used non-prescription medication. Migraine is common in the study population,
      resulting in sickness absence and work disruption, although migraineurs have
      little if any more sickness absence than others. Migraineurs' use of medication
      is sub-optimal, and occupational health departments could assist them with
      education and advice.

PMID- 8580475
TI  - A descriptive study of health problems on car mechanics' hands.
AB  - The purpose of the present study was to investigate occupational health problems
      relating to the hands of car mechanics. A descriptive study was performed among
      all car mechanics in 22 car repair shops using a self-administered questionnaire.
      In total, 172 car mechanics returned the questionnaire (92%). Fourteen per cent
      reported occurrence of white fingers, 24% reported occurrence of paresthesias in
      hands or arms, 41% reported that dry skin on their hands was often a problem, 46%
      reported occurrence of hand eczema, and 28% had experienced more than 20 cuts on
      the hands in the past year. A significant relationship was found between the
      occurrence of hand eczema and employment for less than 14 years as a car
      mechanic. This was also found for occurrence of white fingers and cuts on the
      hands. Further surveillance of the working environment among car mechanics seems
      to be required.

PMID- 8580476
TI  - The use of anti-depressants and benzodiazepines in the perpetrators and victims
      of accidents.
AB  - The objective of this study was to determine whether there is a greater incidence
      of psychotropic drugs in the blood of those 'responsible' for an accident
      compared with those not 'responsible' for an accident. Blood samples were taken
      from people involved in accidents presenting at the accident and emergency
      departments of two teaching hospitals over a five-month period and analysed for
      the presence of alcohol, tricyclic anti-depressants (TCAs) and benzodiazepines
      (BZs). Details of the accident were used to produce a test group (accidents where
      a drug may have contributed) and a control group (accidents where the presence of
      a drug could not have been a factor). In total, 229 samples were collected. The
      only criterion for inclusion in the study was that the accident was of sufficient
      severity to merit the routine taking of a blood sample, in which case an
      additional amount was taken for the purposes of this investigation. In all, 63
      samples (27.5%) were positive for at least one of alcohol, TCA or BZ. Of the
      accidents represented by these samples, 48 could have been caused by the presence
      of the drug (responsible group) and 15 could not (not responsible group). There
      was a significantly greater representation of TCAs and BZs in the blood taken
      from the responsible group compared with the not responsible group (P < 0.0045).

PMID- 8580477
TI  - The special study module: a novel approach to undergraduate teaching in
      occupational medicine.
AB  - Difficulties in teaching occupational medicine to undergraduates stem from the
      reduced availability of teaching time and the perception of the specialty. Recent
      changes in the General Medical Council curricular framework have permitted the
      development of a special study module (options course) in occupational medicine,
      in which a small number of motivated undergraduates elected to participate and
      which was adequately resourced. This course laid particular emphasis on changing
      students' attitudes towards the specialty, self-learning techniques, problem
      solving and other skills such as workplace assessment. The objectives, content
      and teaching methods of the course are described, as is a preliminary evaluation.
      It is suggested that other medical schools should adopt and refine this approach
      in order to improve the quality of undergraduate training in at least a
      proportion of the output of medical schools.

PMID- 8580478
TI  - Multiple pathology related to occupation in an elderly obese seasonal migrant
      worker.

PMID- 8580479
TI  - Regulation of anti-SRBC antibody production by opioids and their mechanisms.
AB  - This study focused on the influences of opioids on the generation of antibody
      against sheep erythrocyte in vitro. It was found that morphine, a-CAO, DADLE,
      MENK were able to inhibit the capacity of murine spleen cells to generate
      antibody and leukotriene C4 and conversely, dynorphin was able to stimulate the
      capacity of murine spleen cells to generate antibody and leukotriene C4.
      Morphine, a-CAO, MENK, DADLE, dynorphin decreased intracellular cAMP level,
      increased [Ca2+]i and calmodulin activity. The effects were completely blocked by
      naloxone, the specific opioid antagonist. Our results showed that opioids
      regulate the production of antibody in murine spleen cells, and alter
      intracellular cAMP, [Ca2+]i calmodulin activity, and leukotriene C4 production by
      way of binding to different receptor types.

PMID- 8580480
TI  - Restriction fragment length polymorphism (RFLP) analysis of genomic DNA of 5
      strains of Trichinella spiralis in China.
AB  - Five restriction endonucleases were used to digest genomic DNA from 5 isolates of
      Trichinella spiralis obtained from Changchun, Tianjin, Xian, Henan and Yunnan.
      All the isolates were secured from pigs except the Changchun strain which came
      from dog. The DNA fragments digested by endonuclease were separated by agarose
      gel electrophoresis. The Changchun isolate had a EcoRI band at 1.12kb and a DraI
      band at 1.97kb which were unique to this isolate. A cloned specific repetitive
      DNA sequence (1.12kb) from the Changchun strain was selected to prepare a probe
      for the Southern blotting of EcoRI restriction DNA fragments for the 5 isolates.
      The 1.12kb hybridizing band did not appear except in the Changchun isolate. These
      results seem to indicate that there are differences between the isolates obtained
      from hosts in different geographical regions.

PMID- 8580481
TI  - Cloning and expression of the gene coding for IL-2(60)-PE40, a molecular targeted
      protein.
AB  - It has recently been shown that chimeric toxin composed of IL2 fused tp PE40, a
      mutant form of Pseudomonas Exotoxin A devoid of its native cell recognition and
      binding domain was cytotoxic to IL2 receptor bearing cells. We here amplified the
      gene IL-2 (60), which codes for the N-terminal 1-60 amino acids of human IL-2 by
      PCR. After that, we fused it to PE40 and the new chimeric protein IL-2(60)-PE40
      was expressed in E. coli. SDS-PAGE revealed that IL-2(60)-PE40 chimeric protein
      accounts for more than 18% of total cell proteins. As the region IL-2 binds with
      its receptor was defined in the N-terminal residues 8-54 of IL-2, such fusion
      proteins will have the same activity with IL-2-PE40. Following primary
      purification, IL-2(60)-PE40 was shown to be very toxic to IL-2 receptor-positive
      cells but non measurable effect on the cells lacking IL-2 receptors. Such a
      structure has not been reported by now. The fusion protein is useful for
      suppressing the immune response in cases of rejection of allografts and organ
      transplants and as therapeutic agents for the treatment of IL-2 receptor related
      diseases such as autoimmune disease, ATL (adult T-cell leukemia), et al.

PMID- 8580482
TI  - Vasoactive intestinal polypeptide prevents injury of pulmonary vascular
      permeability due to xanthine with xanthine oxidase.
AB  - Hyperpermeability is a crux of pathogenesis of sudden lung edema in many
      pulmonary disorders, especially in acute lung injury and adult respiratory
      distress syndrome (ARDS). Using our modified method for assessment of pulmonary
      vascular permeability, we observed the effects of xanthine with xanthine oxidase
      (X-XO) perfused in rat pulmonary artery and the protection of vasoactive
      intestinal polypeptide (VIP) against the injury of pulmonary vascular
      permeability. After addition of xanthine oxidase in the perfusate reservoir
      containing xanthine, 125I-albumin leak index (125IALI) was remarkably increased
      while peak airway pressure (Paw) was not significantly increased, and perfusion
      pressure of pulmonary artery (Ppa) and lung wet/dry weight ratio (W/D) were only
      slightly increased. Xanthine plus xanthine oxidase also increased thromboxane B2
      (TX B2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in the perfusate.
      Treatment with VIP obviously reduced or totally prevented all signs of injury.
      Simultaneously, VIP also diminished or abolished the associated generation of
      arachidonate products. The results indicated that VIP has potent protective
      activity against injury of pulmonary vascular permeability and may be a
      physiological modulator of inflammatory damage to vascular endothelium associated
      with toxic oxygen metabolites.

PMID- 8580483
TI  - The inhibitory effect of astragalus membranaceus on coxsackie B-3 virus RNA
      replication.
AB  - Using mice infected with coxsackie B-3 virus (CVB3) as a viral myocarditis model,
      we observed the inhibitory effect of Astragalus membranaceus (AM) on CVB3-RNA
      replication in myocardial tissue of mice by RNA-RNA in situ hybridization with
      negative-strand RNA probes labelled with 35S and quantitative imaging analysis of
      positive signals. The mechanism of its effect on CVB3-RNA replication has been
      investigated by detection of beta-interferon (beta-IFN) as well. Results showed
      that the copy numbers of CVB3-RNA as well as the histologic scores (necrosis) in
      myocardial tissues of infected-AM treated mice were significantly lower than
      those in infected and normal saline treated mice, suggesting that AM could
      inhibit the replication of CVB3-RNA, but its effect on CVB3-RNA replication had
      no correlation with induction of beta-IFN.

PMID- 8580484
TI  - In patients with hypertensive left ventricular hypertrophy and coronary heart
      disease, coronary flow reserve is similarly impaired.
AB  - Coronary blood flow reserve (CFR) was assessed by transesophageal Doppler
      echocardiography in normal subjects (group A, n = 20), hypertensive non-left
      ventricular hypertrophy (non-LVH) patients (group B, n = 22), hypertensive
      patients with LVH (group C, n = 32) and coronary heart disease patients (group D,
      n = 33) with the volume sample placed at the bifurcation of the left main and
      left descending coronary artery. Coronary blood flow velocity (CBFV) was
      evaluated at rest, 2 minutes after dipyridamole (0.56 mg/kg, i.v.), and 2 minutes
      after aminophylline i.v. The ratio of dipyridamole to rest maximal diastolic
      velocity (D/R PDV) was considered the index of coronary blood flow reserve. It
      was found that D/R PDV was significantly less in groups C and D compared with
      that in groups A and B(D/R PDV, 1.84 +/- 0.57, 1.57 +/- 0.41 versus 2.59 +/- 0.70
      and 2.22 +/- 0.58, respectively), with no difference in D/R PDV between groups C
      and D. Twenty-four out of 32 patients in group C with D/R PDV were less than 2.0
      compared to 29 out of 33 patients in group D (P > 0.05). Significant negative
      correlation was found between D/R PDV, D/R PSV and interseptal thickness, left
      ventricular mass index in hypertensive patients. These data show that impaired
      CFR in hypertensive patients with LVH is comparable to that in patients with
      coronary heart disease.

PMID- 8580485
TI  - Clinical significance of complete left bundle branch block in dilated
      cardiomyopathy.
AB  - Clinical, electrocardiographic and echocardiographic findings in 64 patients with
      dilated cardiomyopathy were restrospectively studied. Compared with 51 patients
      without complete left bundle branch block (CLBBB), 13 patients with CLBBB had
      higher New York Heart Association (NYHA) functional class (P < 0.05), increased
      left ventricular end-diastolic and end-systolic diameters (P < 0.002) and
      myocardial mass (P < 0.02), severe mitral regurgitation (P < 0.01) and higher
      mortality rate (P < 0.04). Multivariate stepwise regression analysis revealed
      that the presence of CLBBB was an independent prognostic factor for patients with
      dilated cardiomyopathy.

PMID- 8580486
TI  - Changes of plasma endothelin and atrial natriuretic peptide during the onset and
      after termination of paroxysmal supraventricular tachycardia.
AB  - Radioimmunoassays were used to measure the concentration changes of plasma
      endothelin (ET) and atrial natriuretic peptide (ANP) during the onset and after
      termination of paroxysmal supraventricular tachycardia (SVT). 30 cases were
      reviewed and comparisons with 42 normal subjects were made. There are very
      significant differences (P < 0.0001) in the concentration changes of both plasma
      ET and ANP during the onset and 30 minutes after the termination of SVT. During
      the onset period of SVT, the plasma ET and ANP were markedly elevated and 30
      minutes after its termination they were lowered significantly, but their
      concentrations were still 2-fold higher than those of the control group. As the
      biological effects of ANP and ET are antagonistic to each other, their parallel
      elevation and lowering of plasma concentrations during and after the termination
      of SVT reveal that these 2 hormones participate in the pathophysiological process
      of SVT. This phenomenon is possibly one of the homeostatic regulatory functions
      in the organism.

PMID- 8580487
TI  - Study on nude mice inoculated with Mycobacterium leprae by multiple routes.
AB  - Immune-deficient nude mice were inoculated with nude mouse derived Mycobacterium
      leprae by multiple routes (intravenously, subcutaneously at the foot pads and
      ears). The results showed that these inoculated animals were capable of producing
      a great number of Mycobacterium leprae to a level 10 per gram of tissue and were
      detected histopathologically to have heavy lepromatous lesions. The dissemination
      of the infection was found particularly in sites with lower body temperature. The
      organisms have a partiality to striated muscles and peripheral nerves. The
      authors suggest that experimental leprosy in nude mice is a very useful tool for
      leprosy research, especially in countries without armadillos. Compared with the
      single-route inoculation reported previously, multiple-route inoculation is more
      available.

PMID- 8580488
TI  - Preoperative segmental localization of focal hepatic lesion on MRI.
AB  - In order to evaluate the accuracy of preoperative segmental localization of
      hepatic mass lesions, 68 cases were prospectively studied and evaluated by the
      correlation of magnetic resonance imaging (MRI) and surgical findings. Right,
      middle and left hepatic veins were seen in 100%, 97% and 94% of the subjects
      respectively on MRI. The right and left portal veins were seen in 100% and 95.6%
      respectively. The accuracy in determining the segmental location of hepatic
      lesions was 89.7%. The accuracy could be increased to 91.3% if the lesion was
      located at single segment whereas it was only 86.4% when the lesion extended
      across several segments. It is possible to say that MRI is an important modality
      in the preoperative segmental localization of masses.

PMID- 8580489
TI  - Changes of nitric oxide and protective effects of nitric oxide inhibitors in
      newborn rats with sepsis.
AB  - In a newborn rat model of sepsis, the changes of nitric oxide and the protective
      effects of methylene blue or/and dexamethason were investigated. The results
      revealed that plasma nitric oxide levels were elevated at 6 h and peaked at 12 h
      after bacterial challenge. The treatment with methylene or/and dexamethasone was
      found to blunt hypoglycemia and hyperlacticemia, to reduce the occurrence rate of
      loss of response to pain, and to prolong the survival time. Moreover, therapy by
      dexamethasone was shown to decrease the 24 h mortality. The results suggested
      that nitric oxide play an important role during the course of fatal P. aeruginosa
      sepsis, but it is clear that the clinical value of nitric oxide and its
      inhibitors need to be further studied.

PMID- 8580490
TI  - Establishment of a human T-lymphoma cell line (H-TL90) and analysis of its
      biological characteristics.
AB  - We established a human T-lymphoma cell line from the cancerous ascites of a male
      patient with prostate cancer which was named H-TL90. This cell line was
      characterized by its histological features, and by chromosomal and immunological
      analysis. Immunophenotypic analysis revealed that the cells expressed surface
      antigen CD-3CD-4CD+7CD-8. Biological analysis revealed that the cell can promote
      lymphocyte proliferation. This suggested that the cell line has an autosecretion
      function. Cytogenetic analysis revealed that H-TL90 was a hyperdiploid with 47
      chromosomes and had characteristic translocation between chromosome 3 and 11, and
      the deletion of the long arm of chromosome 6. These results demonstrated the H
      TL90 cell line can be a useful model for the study of human T-lymphoma.

PMID- 8580491
TI  - A comparison of the effects of the propofol versus midazolam during total
      intravenous anesthesia for gynecological surgery procedures.
AB  - The effects of propofol and midazolam as an intravenous anesthetic were compared
      in 40 ASA I-II patients undergoing gynecological surgery during total intravenous
      anesthesia (TIVA). They were divided into propofol group (P n = 20) and midazolam
      group (M n = 20) randomly. The anesthesia was designed for each group
      respectively. Here, we discuss the experimental method and the results, which
      indicate that propofol is not only an effective anesthetic but also has more
      rapid and head-clear recovery properties than midazolam.

PMID- 8580492
TI  - Treatment of 23 patients with advanced gastric cancer by intravenously transfer
      of autologous tumor-infiltrating lymphocytes combined with rIL-2.
AB  - Tumor-infiltrating lymphocytes (TIL) isolated from metastatic lymph nodes in
      patients with nonoperable advanced gastric cancer were induced to become LAK-like
      cytotoxic activity of TIL after in vitro culture with rIL-2. Twenty-three
      patients with advanced gastric cancer were treated by intravenously transfer of
      autologous TIL combined with rIL-2. The tumor focus disappeared (complete
      remission, CR) in 3 patients (13.0%) and significantly decreased (partial
      remission, PR) in 5 patients (21.7%). Fifteen patients did not respond to the
      treatment. The amount of soluable IL-2 receptor in serum was significantly
      decreased after treatment, the cytotoxicity of NK cells and OT test were
      significantly increased. No significant difference in CD4/CD8 was found between
      before and after treatment. No serious side effect was observed in the treatment.

PMID- 8580493
TI  - Abdominal scar endometriosis: report of 28 cases.
AB  - Twenty-eight cases of abdominal scar endometriosis from January, 1980 to
      December, 1993 are reported. Of these patients, twenty-four underwent term
      cesarean section, and four underwent a midtrimester abortion by abdominal
      hysterotomy. The majority of patients manifested symptoms 1 year after the
      operation. The most common was a painful mass of scar tissue that became swollen
      and tender during menstruation. The pathogenesis, diagnosis and treatment are
      discussed. In correlation with the pathological findings, the effects of drug
      therapy are evaluated. It was found that surgical excision is the best method of
      treatment.

PMID- 8580494
TI  - Immune response in insects: the role of phenoloxidase in defense reactions in
      relation to melanization and sclerotization.
AB  - It is well known that activated prophenoloxidase (proPO) plays an important role
      in cuticular melanization and sclerotization. In addition, studies dealing with
      immune response of insects suggest that phenoloxidase (PO) is also critical in
      the defense reactions of insects against invaders. proPO is activated by
      elicitors derived from microbial cell wall components such as peptidoglycan, beta
      1,3-glucan, and lipopolysaccharide (LPS). According to our recent studies we
      proposed a model clarifying the role of PO in both cellular and humoral immune
      responses. LPS triggers Ceratitis capitata hemocytes via induced protein tyrosine
      phosphorylation to release biologically active molecules, including p47 and proPO
      activators. Furthermore, hemocytes in response to LPS facilitate clearance of LPS
      from the hemocoel of medfly. The effector molecules involved in the LPS clearance
      are hemocyte surface-associated p47 (mp47), soluble p47 (sp47), activated proPO,
      and tyrosine. A similar LPS clearance system in the integument of medfly in vitro
      was also demonstrated. According to our data, the proposed mechanism for LPS
      clearance from hemocoel and from integument is the crosslinking of LPS to p47 or
      certain integumental proteins via the intermediacy of reactive tyrosine
      derivatives generated by PO activity, as is the case for cuticular protein-chitin
      crosslinks during sclerotization. We also demonstrated that metabolites of the
      eumelanin biosynthesis and not melanin itself or N-acetyldopamine (NADA), the key
      precursor of sclerotizing agent, were necessary for the immune responses by
      hemocytes and integument.

PMID- 8580495
TI  - Isolation and identification of a cAMP generating peptide from the flesh fly,
      Neobellieria bullata (Diptera: Sarcophagidae).
AB  - The Manduca sexta Malpighian tubule assay system, developed to monitor adenylate
      cyclase activity, was used in combination with HPLC to isolate a novel cAMP
      generating peptide from 350,000 whole flesh flies, Neobellieria bullata. Mass
      spectrometry revealed a molecular mass of 5,047 daltons, and Edman degradation
      the following sequence: AGAEAEKLSGLSKYFNGTTMAGRANVAKATYAVIGLIIAYNVMKPKKK. This 48
      mer peptide, called Neb-cGP, does not belong to the corticotropin releasing
      factor family of insect diuretic peptides. Electrophoresis and subsequent
      immunoblotting of peptides immunoprecipitated from a homogenate of entire flies
      showed that one fly contained approximately 0.003 to 0.03 micrograms Neb-cGP and
      that 10 micrograms represents the lowest immunostainable amount on a Western
      blot.

PMID- 8580496
TI  - Isolation and characterization of Locusta migratoria accessory gland myotropin I
      (Lom-Ag-MT-I) from the brain of the Colorado potato beetle, Leptinotarsa
      decemlineata.
AB  - A novel myotropic Colorado potato beetle peptide, active in the Locusta oviduct
      motility assay, was isolated from a methanolic extract of 9,000 brain complexes
      of adult Leptinotarsa decemlineata by means of HPLC. Its sequence is Gly-Phe-Lys
      Asn-Val-Ala-Leu-Ser-Thr-Ala-Arg-Gly-Phe-NH2. This peptide is identical to Lom-AG
      MT-I, a myotropin previously isolated from the male accessory glands of Locusta
      migratoria, using the L. migratoria oviduct motility bioassay as a monitoring
      system. It strongly stimulated the frequency, amplitude, and tonus of the
      myogenic oviduct contractions, even at low concentrations.

PMID- 8580498
TI  - Evaluating benefit from amplification.

PMID- 8580497
TI  - Catecholamine metabolism and in vitro induction of premature cuticle melanization
      in wild type and pigmentation mutants of Drosophila melanogaster.
AB  - The major pathway leading to adult cuticle melanization in Drosophila
      melanogaster has been investigated by a combination of biochemical and genetic
      approaches. By comparing catecholamine pools in newly emerged flies and in frass
      (excreta) collected 1 to 4 days after eclosion from wild type with those obtained
      from several pigmentation mutants, the major flow of catecholamines through the
      pathway to an unidentified final catabolite was determined. We also demonstrate
      that incubation with dopamine in vitro induces premature melanization in wild
      type unpigmented pharate adults several hours before the developmentally
      programmed onset of melanization, supporting the hypothesis that the availability
      of catecholamines may be the limiting factor determining the onset of
      melanization and that the major enzymatic activities that act downstream of dopa
      decarboxylase in the pathway are deposited into the cuticle before pigmentation
      begins. In vitro melanization studies with various pigmentation mutants that are
      associated with critical enzymatic steps in Drosophila catecholamine metabolism
      are consistent with their proposed function and suggest a central role of N-beta
      alanyldopamine in adult cuticle pigmentation.

PMID- 8580499
TI  - Binaural phase effects in the auditory brainstem response.
AB  - This study investigated the possibility of a correlate of the masking level
      difference (MLD) in the auditory brainstem response (ABR), given that behavioral
      data indicate the brainstem origination of the MLD. Previous studies have
      reported MLD characteristics in the late auditory evoked potentials. In the
      present study, stimuli were presented in S(o)N(o) and S pi N(o) to female adults
      with normal hearing. In experiment 1, a binaural phasic difference potential
      (BPD) was derived by subtracting the suprathreshold ABRs to S(o)N(o) from S pi
      N(o) for tone pips of 500 to 4000 Hz. The magnitude of the BPD was inversely
      related to frequency. In experiment 2, thresholds to 500-Hz tone pips in S(o)N(o)
      and S pi N(o) were equal. In a case study of a subject with no behavioral MLD,
      the 500-Hz BPD was abnormal on one side, suggesting unilateral interruption of
      phase synchrony in the brain stem. Thus, the results of this study, in
      conjunction with previous studies on late potential correlates of the MLD,
      suggest that the ability to maintain phase information through the brain stem is
      necessary but not sufficient to generate the MLD.

PMID- 8580500
TI  - Effects of pre-existing hearing loss and gender on proposed ANSI S12.13 outcomes
      for characterizing hearing conservation program effectiveness: preliminary
      investigation.
AB  - Draft American National Standard "Evaluating the Effectiveness of Hearing
      Conservation Programs" identifies potentially important links between audiometric
      threshold variability outcomes and occupational hearing conservation program
      (HCP) practices. Unacceptable threshold variability in annual audiograms may
      identify poor testing practices and temporary threshold shifts. This preliminary
      investigation reveals pre-existing hearing loss to be a potentially important
      confounding viable to interpreting ANSI S12.13 outcomes. Poor hearing groups in
      this study consistently yielded greater threshold variability (i.e., "poorer" HCP
      performance) than better hearing groups. Gender may also be a confounding
      variable, however, to a far lesser degree. HCP managers should exercise caution
      when interpreting relative ANSI S12.13 outcomes among HCPs differing in baseline
      hearing sensitivity. Potential causes for these findings are discussed, and
      implications for future research are identified.

PMID- 8580501
TI  - Speech recognition in noise by hearing-impaired and noise-masked normal-hearing
      listeners.
AB  - A prevailing complaint among individuals with sensorineural hearing loss (SNHL)
      is difficulty understanding speech, particularly under adverse listening
      conditions. The present investigation compared the speech-recognition abilities
      of listeners with mild to moderate degrees of SNHL to normal-hearing individuals
      with simulated hearing impairments, accomplished using spectrally shaped masking
      noise. Speech-perception ability was assessed using the predictability-high
      sentences from the Speech Perception in Noise test. Results revealed significant
      differences between groups in sentential-recognition ability, with the hearing
      impaired subjects performing poorer than the masked-normal listeners. These
      findings suggest the presence of a secondary distortion degrading sentential
      recognition ability in the hearing impaired, implications of these data will be
      discussed concerning the mechanism(s) responsible for speech perception in the
      hearing impaired.

PMID- 8580502
TI  - Target-matched insertion gain derived from three different hearing aid selection
      procedures.
AB  - Three hearing aid selection procedures were compared to determine if any one was
      superior in producing prescribed real-ear insertion gain. For each of three
      subject groups, 12 in-the-ear style hearing aids with Class D circuitry and
      similar dispenser controls were ordered from one of three manufacturers. Subject
      groups were classified based on the type of information included on the hearing
      aid order form: (1) the subject's audiogram, (2) a three-part matrix specifying
      the desired maximum output, full-on gain, and frequency response slope of the
      hearing aid, or (3) the desired 2-cc coupler full-in grain of the hearing aid,
      based on real-ear coupler difference (RECD) measurements. Following
      electroacoustic adjustments aimed at approximating a commonly used target
      insertion gain formula, results revealed no significant differences among any of
      the three selection procedures with respect to obtaining acceptable insertion
      gain values.

PMID- 8580503
TI  - Understanding of time-compressed speech by older adults: effect of discard
      interval.
AB  - Fifteen subjects, aged 60 to 74 years, participated in a study to assess the role
      of discard interval (DI) length in the understanding of time-compressed connected
      speech by older adults. The subjects' task was to report associations among the
      items mentioned in a passage. Results indicate that performance deteriorated
      gradually until a critical DI of 75 msec was reached, beyond which performance
      dropped sharply. Results should help in the better understanding of speech
      perception by older listeners and may be useful in development of a standardized
      test for evaluating speech understanding in older individuals whose auditory
      complaints are often not explained by their peripheral hearing loss.

PMID- 8580504
TI  - Recognition of speech in noise with hearing aids using dual microphones.
AB  - Fifty subjects with mild to moderately severe sensorineural hearing loss and
      prior experience with amplification were evaluated at two sites (25 subjects at
      each site). Speech recognition in noise scores were measured using the Hearing in
      Noise Test (HINT) for each subject while wearing binaural behind-the-ear hearing
      aids allowing switching between two fitting algorithms ("basic" and "party") and
      two microphone conditions (single microphone omnidirectional and dual-microphone
      directional). Results revealed an average improvement in signal-to-noise ration
      (SNR) of 7.4 to 8.5 dB at the two sites for the directional conditions in
      comparison to the omnidirectional conditions. No significant improvement in SNR
      was measured between the two fitting algorithms. In addition, the Profile of
      Hearing Aid Benefit (PHAB) (Site I) and the Abbreviated Profile of Hearing Aid
      Benefit (APHAB) (Site II) were administered. Results revealed that the benefit
      scores for background noise and reduced cues (Site I) and background noise and
      aversiveness of sounds (Site II) were significantly higher than those reported in
      the established norms. Finally, 76 percent of the subjects of Site I reported
      that the experimental hearing aids provided "significantly better" or "better"
      performance than their current hearing aids.

PMID- 8580505
TI  - Microvascularization of corpuscles of Stannius in teleost fishes.
AB  - Blood supply and microvascular patterns of Stannius corpuscles were studied by
      scanning electron microscopy of vascular corrosion casts in the teleost fishes
      Blennius pavo, Zosterisessor ophiocephalus, and Gasterosteus aculeatus.
      Microvascular casts demonstrated that Stannius corpuscles--depending on their
      location--have an arterial supply derived either directly from the dorsal aorta,
      from the trunk of the first ventral segmental artery of the tail, or from a renal
      artery. Supplying arteries form a capsular capillary bed and a parenchymal
      capillary bed; both are composed of fine, freely anastomosing vessels with a
      homogeneous isotropic distribution. Central venules arise deep in the corpuscles.
      In the capsule, they form a single vein which drains into a segmental vein or
      directly into the caudal vein. Stanniocalcin, the hormone of the Stannius
      corpuscle, enters the renal circulation and reaches its main target organs, the
      gills, via posterior cardinal veins--heart--ventral aorta. Occasionally, some
      capsular venules empty into the trunk kidney peritubular venules. Capillaries are
      fenestrated and are embraced by pericytes with long, slender processes. The
      perivascular space contains collagen fibrils. Nerve fibers are found close to
      endothelial cells and pericytes. Vascular patterns of Stannius corpuscles are
      compared with those of the rat parathyroid glands and are discussed in respect to
      physiological implications.

PMID- 8580506
TI  - Blood vascular bed and pericapillary space in rat parathyroid glands.
AB  - The blood vascular bed and pericapillary space of the rat parathyroid gland were
      studied by scanning electron microscopy of vascular casts, freeze-cracked tissue
      blocks, and NaOH-treated tissue specimens. The findings were supplemented by
      transmission light and electron microscopy of sectioned tissue samples. The rat
      parathyroid gland contained a rich network of freely anastomosing capillaries.
      These capillaries were surrounded by marked pericapillary spaces that were
      demarcated by basal lamina of both capillaries and parenchymal cells. The
      pericapillary spaces contained many collagen fibrils and frequently issued some
      projections running deep into the sheets of parathyroid cells. The latter
      projections may be useful to supply the parenchymal cells located far from the
      capillaries. The collagen fibrils may regulate the flow of tissue fluid in the
      pericapillary space and convey parathyroid hormone, which is released at the
      apicolateral domain, into the capillaries.

PMID- 8580507
TI  - Mammalian parathyroids: morphological and functional implications.
AB  - Fixation with aldehydes is achieved either by immersion or perfusion. The
      parenchyma of parathyroid glands fixed by immersion consists of dark cells
      containing a lot of membranes of these organelles which are concerned with
      hormone secretion, light cells which are poor in these organelles, intermediate
      forms between the two, and multinuclear syncytial cells. They have been
      attributed to represent different functional stages of secretory activity, the
      dark cell being in an active form, the light cell in a resting form. Studies of
      the parathyroids of mice, rats, rabbits, cats, dogs, pigs, cattle, sheep, goats,
      and horses employing various fixation protocols clearly demonstrate that light
      cell variants and multinuclear syncytial cells are formed during improper
      immersion fixation as a result of membrane disintegration. Parathyroids fixed by
      perfusion or by immersion in an appropriate fixation medium comprise only one
      cell type which correspond to the dark chief cell. Parathyroid cells are polar
      cells bearing some of the rough endoplasmic reticulum in the basal pole, the rest
      of it, the Golgi complex, and secretory granules in the apical pole. The
      secretory product is released by exocytosis at the apicolateral domain of the
      plasma membrane into the intercellular space. Secretory activity can be altered
      experimentally, leading to drastic changes in the amount of cell membrane related
      to hormone synthesis, intracellular transport, exocytic release, and secretion
      coupled membrane retrieval. The sensitive reaction of parathyroid cells to both
      the mode of fixation and to fixation media demands careful evaluation of the
      fixation protocol. This and the polarity of parathyroid cells have to be borne in
      mind for estimating secretory activity on the basis of morphological criteria.

PMID- 8580508
TI  - Quantitative and three-dimensional aspects of the rat parathyroid gland in normo
      , hypo-, and hypercalcemia.
AB  - The ultrastructure of the rat parathyroid has been under study for more than 35
      years, but controversies still exist, especially regarding structure-function
      relationships. The present review focuses on recent morphological parathyroid
      research on rats under normal conditions and in various states of disturbed
      calcium metabolism. To facilitate discussions on functional aspects, current
      biochemical data, particularly those dealing with the regulation of parathyroid
      hormone synthesis and release, are also considered. Our results from quantitative
      studies and from investigations employing serial sectioning form the basis for
      the discussions. A central issue is whether the parathyroid secretory cells
      undergo secretory cycles. Prompted by results obtained from improved fixation
      procedures and serial sectioning, we question the basis for the theory of
      secretory cycles. Since the rat parathyroid secretory cell is polar, a single
      section is not an appropriate sample for estimating functional activity and for
      comparing the structure and distribution of intracellular components of adjacent
      cells. The heterogeneity in ultrastructural appearance of intracellular vesicles
      calls for the use of specific markers in relating the structure of the vesicular
      compartment to intracellular processing of hormone. The importance of unbiased
      quantitative techniques is illustrated in discussions on cell number and size for
      estimating the response of the parathyroid gland to different functional states
      or disorders demanding changes in secretion of parathyroid hormone, e.g., hyper-
      and hypocalcemia.

PMID- 8580509
TI  - The biological significance of storage granules in rat parathyroid cells.
AB  - Both prosecretory and storage granules are concomitantly formed at the trans
      Golgi network including the innermost Golgi cisterna. Prosecretory granules
      develop into small secretory granules that release their contents by exocytosis
      finely regulated by a complex mechanism for maintaining calcium homeostasis. In
      the rat parathyroid cells, storage granules are large secretory granules storing
      parathyroid hormone for an emergency supply. The hormone is rapidly discharged by
      exocytosis when serum calcium concentration is decreased. The granules are
      constantly produced even under conditions of low serum calcium concentration in
      the regions of 8 mg/dl. The granule content is constantly hydrolyzed when not
      discharged, leading to a decreased core and finally to the formation of vacuolar
      bodies. The fate of the vacuolar bodies is unknown. Hypercalcemic conditions
      accelerate hydrolysis. The threshold value of calcium concentration required for
      the release of storage granule contents is between 8.0 and 7.5 mg/dl and that of
      calcium concentration for accelerating degradation of storage granules is about
      11.5 mg/dl. Sympathetic stimulation causes storage granules to be discharged
      regardless of hypercalcemia or hypocalcemia. Parasympathetic stimulation
      accelerates hydrolysis. The degradation of storage granules seems to be closely
      associated with an intracellular regulatory mechanism for parathyroid hormone
      secretion.

PMID- 8580510
TI  - Ultrastructure of human parathyroid cells in health and disease.
AB  - Parathyroid glands (n = 271) removed from 130 patients were examined by light and
      electron microscopy. A standardized method of tissue processing was employed and
      morphometry was performed. The aim of the paper is to provide a description of
      the human parathyroid chief cell ultrastructure in health and disease, with
      quantitative evaluation of structures involved in secretion of parathyroid
      hormone in a large case series, and to discuss their role in current diagnostic
      histopathology. The patients were euparathyroid (n = 10), or affected by primary
      (n = 97), secondary (n = 8), or tertiary (n = 15) hyperparathyroidism. In normal
      glands, solid parenchyma was composed of chief cells, large clear cells,
      transitional-oxyphil cells, and oxyphil cells. Chief cell hyperplasia, pseudo
      adenomatous hyperplasia, adenoma, water-clear cell hyperplasia, and carcinoma
      were the most usual forms of parathyroid disease responsible for primary
      hyperparathyroidism. In chief cell hyperplasia, all the parathyroid glands were
      enlarged and the chief cells were in an active state of hormone secretion, with a
      large Golgi complex, abundant rough endoplasmic reticulum (RER), small lipid
      droplets, and tortuous plasma membrane. In pseudo-adenomatous hyperplasia, one
      gland was enlarged and the others displayed a normal size; however, electron
      microscopic examination and morphometric analysis showed that all the glands had
      active cells. Adenomas displayed a pattern similar to those of pseudo-adenomatous
      hyperplasia, with one gland enlarged and the others of normal size. However,
      ultrastructural examination and morphometry showed that the normal-size glands
      were hypo-active. Water-clear cell hyperplasia showed cells filled with
      cytoplasmic vacuoles. In these cells, structures with intermediate features
      between secretory granules and vacuoles were visible. Nucleo-cytoplasmic atypias
      were frequently visible in parathyroid carcinoma cells. In secondary and tertiary
      hyperplasia, active chief cells were regularly mixed with oxyphil or transitional
      oxyphil cells. The tertiary hyperplasia was characterized by RER-associated
      structures that were not found in the normal or other pathological conditions.
      These results demonstrate that electron microscopy and morphometry represent
      useful tools in parathyroid histopathology.

PMID- 8580511
TI  - Morphology of parathyroids in man and animals. Introduction.

PMID- 8580512
TI  - Amphibian parathyroids: morphological and functional aspects.
AB  - Amphibians living partially or totally in a terrestrial environment are the first
      tetrapods to possess parathyroid glands. Purely aquatic amphibians and amphibian
      larvae lack these endocrine glands. The parathyroids develop at the time of
      metamorphosis. The parathyroid glands in caecilians consist of a single cell
      type, that of urodeles may be composed of basal (supporting) cells and suprabasal
      (chief) cells, and that of anurans of small and large chief cells. Parathyroid
      glands of caecilians and anurans lack connective tissue, blood vessels, and
      nerves. The parathyroid cells become activated in response to decreased blood
      calcium concentration and undergo changes indicating increased parathyroid
      hormone secretion. Increased blood calcium concentration suppresses secretory
      activity. Usually, parathyroidectomy elicits hypocalcemia in most amphibians.
      Such operations have no effect in lower urodeles. Parathyroid hormone
      administration provokes hypercalcemia in most amphibians. The parathyroids of
      caecilians have not been studied in detail. The urodeles and anurans exhibit
      seasonal changes in the parathyroid glands. These changes may be initiated by
      environmental stimuli such as light, temperature, or alterations in blood calcium
      levels caused by natural hibernation.

PMID- 8580513
TI  - Morphology and physiological significance of parathyroid glands in reptilia.
AB  - Adult reptiles possess one or two pairs of parathyroid glands that have been
      shown in many species to derive from the third and fourth pharyngeal pouches,
      respectively. Up to five pairs may develop during early embryonic life. Excess
      glands may involute during late embryogenesis. The location of the parathyroid
      glands differs in the various species. As a general rule, they lie just anterior
      to the heart, the anterior pair (parathyroid III) being associated with the
      carotid artery, the posterior pair (parathyroid IV) with the aortic arch. In
      snakes, however, the anterior pair (parathyroid III) is associated with the
      carotid artery near the angle of the jaw. As shown by light microscopy and, to a
      lesser extent, by electron microscopy, the parathyroid parenchyma comprises
      secretory cells which may form dark and light variants, occasional oxyphil cells,
      and stellate cells. They are arranged in cords separated by connective tissue
      containing a capillary network. Parathyroid secretory cells often form follicles
      which might be the result of degeneration. Degeneration may occur as a form of
      involution during winter in species undergoing seasonal changes. The product of
      parathyroid cells, the parathyroid hormone, is responsible for the maintenance of
      blood calcium concentration. The sites of action--bones, kidneys, intestine,
      endolymphatics, and dermal skeleton--are not well understood or not investigated.
      In some turtles, parathyroid hormone is not the (main) factor for the regulation
      of calcium homeostasis.

PMID- 8580514
TI  - [Serum and hypophyseal profiles of alpha-melanotropin and prolactin during the
      reproductive cycle of Leptodactylus ocellatus].
AB  - In this work, the seric and hypophysial concentrations of the hormones alpha
      melantopin and prolactin of male specimens of Leptodactylus ocellatus from the
      province of Cordoba are studied during a complete annual period. This amphibian
      presents a continuous reproductive cycle with a wave of greater spermatogenic
      activity in early summer months (December-January). The results corresponding to
      hormones show a very similar pattern: both present their maximal seric value in
      the December-January period, coincidently with the greatest spermatogenic wave.
      Maximal hypophysial values precede seric concentration maximum by two months.
      Although the influence of these hormones on amphibian spermatogenesis is not well
      understood, the observations here described would indicate that alpha
      melanotropin as well as prolactin could play a role in the spermatogenic process
      in Leptodactylus ocellatus.

PMID- 8580515
TI  - The beta 2 receptor plays a role in the hypotensive effect of L-dopa.
AB  - Levodopa is a dopamine precursor exerting its cardiovascular effects by
      conversion to dopamine and by other mechanisms not elucidated yet. Since beta
      receptors are involved in levodopa Central Nervous System actions, we tried to
      find out whether adrenergic receptors are involved in the hypotensive effect of
      levodopa at peripheral level. Experiments were performed on urethane anesthetized
      (1 ml/100 g i.p.) and heparinized (300 U.I./kg i.v.) rats. Heart rate and mean
      carotid blood pressure were registered through a polygraph. Pulmonary ventilation
      was facilitated by a tracheal cannula. Drugs were infused into the femoral vein
      through a polyethylene catheter. Two series of the following drugs were assayed:
      a) Dopamine (3.12 to 25.0 micrograms/100 g i.v.) and levodopa (12.5 to 100
      micrograms/100 g i.v.) as control groups. b) The aforementioned drugs and dosages
      were assayed 20 minutes after intravenous propranolol (50 micrograms/100 g),
      atenolol (100 micrograms/100 g) and ICI 118.55 (25 micrograms/100 g). Dopamine
      produced a dose-related hypotensive effect (p < 0.02) which was not modified by
      propranolol, atenolol or ICI 118.55. Levodopa produced a dose-related blood
      pressure fall which was not changed by atenolol pre-treatment. Contrariwise,
      propranolol and ICI 118.55 evoked a blood pressure raise with levodopa. Since
      propranolol and ICI 118.55 have in common the beta 2 receptor blockade, it is
      suggested that such receptor has a key role in the hypotensive response induced
      by levodopa.

PMID- 8580516
TI  - The abnormal development of male sex organs in the rat using a pure antiandrogen
      and a 5 alpha-reductase inhibitor during gestation.
AB  - The effects of a pure antiandrogen flutamide and the 5 alpha-reductase inhibitor
      finestaride on both prenatal differentiation of prostate and external genitalia
      were studied in the rat. In control male offspring the mean value of anogenital
      distance was 3.1 +/- 0.24 mm, and in control female was 1.2 +/- 0.10 mm. In
      control male newborn rats, histological sections at cranial portion of the
      urethra revealed prostate bud formation. Male offspring prenatally exposed to 6
      mg/Kg/day of flutamide had a significant decrease in anogenital distance, but no
      alteration in prostate bud formation. At higher dosages of flutamide, the
      external genitalia were virtually feminizated and the prostatic budding was
      completely inhibited. In male offspring treated 'in utero' with doses of
      finestaride of 2, 8 and 16 mg/Kg/day, the anogenital distance became
      progressively reduced, but complete abolition of prostate development never
      occurred. However, in male offspring given finestaride at a dose of 2 mg/Kg/day
      concomitantly with flutamide at a dose of 6 mg/Kg/day, prostate differentiation
      was completely abolished.

PMID- 8580517
TI  - Changes induced by zinc on thyroxine deiodination by rat liver in vivo and in
      vitro.
AB  - The effects of in vivo administration or in vitro addition of zinc on 5'
      deiodination of thyroxine (T4) and the concentration of nonprotein sulfhydryl
      groups (NPSH) in rat liver were studied in 200-240 g body weight male Wistar
      rats. Twelve rats were injected i.p. with zinc sulphate 2 mg/kg body weight 24 h
      before the experiments were started. Animals were killed by cervical dislocation
      and the liver was immediately removed and homogenized. Dithiothreitol (DTT) (0,
      2.5, 5 or 10 mM, final concentration) and 1 microCi 125I-T4 were added to
      homogenates. For the in vitro studies, animals were killed by cervical
      dislocation and the liver removed and added zinc or cadmium (2.5 or 5 mM) plus
      DTT and labelled T4. Homogenates were incubated for 90 min at 37 degrees C and
      thereafter chromatographed in Whatman 1 paper. Zinc-injected rats had a
      significant (P < 0.01) decrease in T4 deiodination and in the generation of
      iodine (P < 0.02) and T3 (P < 0.05). In the in vitro studies, both zinc and
      cadmium reduced (P < 0.02) the deiodination of T4, and the generation of iodine
      (P < 0.02) for zinc and P < 0.05 for cadmium) as well as the generation of T3 (p
      < 0.05). The NPSH in zinc-injected rats were within normal levels. Serum T4 and
      T3 in zinc-treated rats were normal, whereas in cadmium-treated rats were both
      significantly decreased (P < 0.01 for T4 and P < 0.02 for T3). The data indicate
      that zinc blocks the activity of liver 5'-deiodinase through a mechanism probably
      related to its binding to the sulfhydryl groups of the enzyme.

PMID- 8580518
TI  - [Relation between cell proliferation and beta adrenergic receptor expression in
      activated T lymphocytes].
AB  - beta adrenergic receptors (R) on murine lymphocytes stimulated with concanavalin
      A (Con A) and tumor lymphoid cell line (BW5147) were characterized by beta
      radioligand binding of 125Icyanopindolol (125I-CYP). The functionality was also
      assesses by hormone-dependent changes in cyclic 3', 5', adenosine monophosphate
      (cAMP) levels on intact cell. Both types of cells displayed a reduced number of
      beta adrenergic receptors by 125I-CYP specific binding. However BW5147 cell line
      were unable to respond to beta agonist stimulation meanwhile the response of
      lymphocytes stimulated with Con A was lower than normal lymphocytes. Despite this
      difference both kind of cells displayed an increase in cAMP production induced by
      Prostaglandin E1 (PGE1). It can be concluded that functional beta R are absent in
      BW5147 cell line. The possible implication of alternative transmission pathway
      and neuroendocrine control in tumor lymphoid cells is discussed.

PMID- 8580519
TI  - Erythrocyte uroporphyrinogen I synthase in rats treated with the hepatic
      carcinogen diethylnitrosamine.
AB  - Uroporphyrinogen I Synthase (URO-S) activity was measured in erythrocytes of
      female and male rats which had received diethylnitrosamine (DENA) as an inducer
      of hepatic tumors. Twenty-two weeks after the last dose of the carcinogen, the
      rats showed statistically significant increases in the URO-S activity.
      Differences in the body weight, erythrocyte porphyrin content or the hematocrit
      between treated and control rats were not found. Fifty percent of female rats and
      thirty percent of male rats treated with DENA were found to have hepatic tumors
      but there was no correlation between blood URO-S activity and tumoral development
      in spite of the increase in URO-S activity observed in DENA treated rats. This
      was observed both in male and female rats.

PMID- 8580520
TI  - [Ethanol mechanism(s) of action on LHRH secretion].

PMID- 8580521
TI  - Body weight loss during acute hypoxia: effects of increased convective oxygen
      transport or previous acclimation.
AB  - Body weight loss and growth retardation occur in rats exposed to simulated high
      altitude, which may be related to the hypoxemia-induced reduction in the
      convective oxygen transport (COT). The present study was thus performed to
      determine whether transfusion polycythemia, increased affinity of hemoglobin for
      oxygen, or previous acclimation to hypobaria (factors that increase COT) are able
      to counteract its effect on body weight during the early period of exposure,
      which appears to be a suitable parameter to test the effectiveness of
      acclimatization. Polycythemia was induced in weanling rats by two ip injections
      of 2.5 ml/100 g b.wt of packed homologous red cells. The rise in hemoglobin O2
      affinity was brought about in adult rats by giving them 0.5 g/dl sodium cyanate
      in the drinking water for 3 weeks. A lower body weight loss during the early
      period of exposure to hypobaria was seen in treated rats than in controls.
      However, body weight loss was still important, which would indicate that
      compensation was probably not complete. When growing rats were acclimated to
      simulated altitude, a sudden increase in body weight was observed when they were
      brought back to ground levels. When animals were taken to altitude again, they
      lost weight at a rate not significantly different to that found in non-acclimated
      ones. The results obtained indicate that treatments do not prevent the studied
      effect of hypoxia and suggest that hypophagia and the resultant initial body
      weight loss and secondary depression of body growth could be considered as
      protective mechanisms against the environmental challenge, although further
      investigation will be necessary to confirm the hypothesis.

PMID- 8580522
TI  - The effects of theophylline and caffeine on the isolated rat diaphragm.
AB  - It is a well known fact that theophylline enhances the force of diaphragmatic
      contraction and delays fatigue. The action of caffeine which is a methylxanthine
      analogue on skeletal muscle are complex. It was claimed in few studies that the
      caffeine was more effective on the diaphragmatic contractility than the
      theophylline. The aim of this study is to compare the effects of theophylline and
      caffeine on the tension generated by fresh and fatigued diaphragmatic muscle.
      Studies were performed in vitro on diaphragmatic muscle strips of rats activated
      by electrical stimuli applied via the phrenic nerve. Isometric twitch
      characteristics (twitch tension, contraction and 1/2 relaxation time) were
      measured. Force-frequency responses were generated using twitches and tetanic
      contractions produced by stimulating the phrenic nerve with 0.2 ms pulses at 10,
      20, 50 and 100 Hz for 1 s with 30 s intervals. Moderate fatigue was then induced
      by repeated submaximal contractions (25 Hz, 160 ms, at the rate of 1/s for 45
      contractions). In fresh muscle 1 mM theophylline and 1 mM caffeine increased
      diaphragmatic tension 40.98 +/- 8.50% and 82.30 +/- 12.21% of the initial value
      respectively. Theophylline did not alter contraction time but prolonged 1/2
      relaxation time, whereas caffeine had no effect on any one. Theophylline induced
      force production in all frequencies. Caffeine caused an increase in force only in
      < 20 Hz, but a decrease in 50 and 100 Hz. In brief submaximal fatigue, both 1 mM
      theophylline and 1 mM caffeine partly prevented fatigue (effect of caffeine was
      more potent). This study suggests that caffeine has a greater effect than
      theophylline on the muscle. Possible mechanism(s) of action of theophylline and
      caffeine on diaphragmatic contractility and fatigue were discussed. It may well
      be the fact that they might have different mechanisms of action on the isolated
      rat diaphragm.

PMID- 8580523
TI  - Extraction of plasminogen activator in the rat's submaxillary gland.
AB  - Plasminogen is activated into the fibrinolytic enzyme plasmin via: a tissue type
      activator and F-XII dependent and F-XII independent systems. The purpose of this
      study was extract and quantify the tissue-type plasminogen activator present in
      the salivary glands of rats. The extracted plasminogen activator-EPA- was
      obtained by homogenizing 1 vol of tissue with 1 vol of 2M KSCN solution. Solution
      with EPA was applied by triplicated in the standard plasminogen-rich and
      plasminogen-free fibrin plates. The degree of fibrinolytic activity was observed
      as areas of liquefaction and measured as the product (mm2) of the two
      perpendicular diameter of the lysed zones. The submaxillary's EPA produced a mean
      lytic area of 198 mm2 +/- 18 SEM only in the plasminogen-rich fibrin plate. This
      activity extrapolated into a standard dilution curve, represented the equivalent
      to a 50 mg/ml plasmin solution. No lysis was induced by EPA from parotid and
      sublingual glands. The antifibrinolytic drug E-ACA in a dose dependent inhibitory
      action, significantly reduced the lytic activity induced by submaxillary's EPA.
      The observation that EPA produced areas of liquefaction only in plasminogen-rich
      fibrin plate and that this activity was inhibited by E-ACA is clear indication
      that the zones of lysis was specific fibrinolysis -activation of plasminogen into
      plasmin- and not due to non-specific proteolysis.

PMID- 8580524
TI  - Effect of potassium permanganate, cobalt chloride and vitamin B complex on the
      haematological parameters of cadmium treated common carp, Cyprinus carpio.
AB  - Effect of potassium permanganate, cobalt chloride and vitamin B complex on the
      haematological parameters of common carp Cyprinus carpio were markedly influenced
      by a treatment of 2.5 mg/l Cd in the laboratory for 96 hours. Hb% and ESR values
      were increased but the RBC and PCV values were reduced. Treatment of KMnO4 (1
      mg/l) or CoCl2 (2 mg/l) induced a further reduction of RBC of the Cd treated
      fish. But parameters like PCV, MCV and MCH of Cd treated fish were not affected
      by the treatment of KMnO4 and CoCl2. Intramuscular injection of vitamin B complex
      did not produce any impact on ESR and MCV values of the Cd treated exposed fish
      but most of the other parameters of such fish were found comparable to control
      indicating that vitamin B complex could counteract Cd to reduce its ill effect.

PMID- 8580525
TI  - Enhancement of erythroid colony growth by triiodothyronine in cell cultures from
      bone marrow of normal and anemic rats with chronic renal failure.
AB  - In order to make a contribution in clarifying the role of thyroid hormones on
      modulation of erythropoiesis and to gain a further insight on the effects of
      these hormones in the anemia of chronic renal failure (CRF), we studied the
      action of triiodo-1-thyronine (LT3) and DT3, a dextrorotary non-calorigenic
      isomer of T3 on late (CFU-E) and early (BFU-E) committed erythroid precursor
      cells from bone marrow of normal and anemic uremic rats. Cultures were prepared
      using the methylcellulose technique containing a standard dose (182 mU/ml) of
      erythropoietin (Ep), LT3 and DT3 in doses of 0.5 and 1.5 micrograms/ml. Thyroid
      hormones were added to cultures in the absence of Ep. Our results demonstrated
      that LT3 and DT3 produced a direct and significant stimulation of CFU-E formation
      and a moderate increase of BFU-E. A dose-correlation was apparent in cultures
      containing thyroid hormones. DT3 was somewhat less active than LT3. As expected,
      Ep also produced a significant increase in erythroid colony formation, mainly CFU
      E. It is notheworthy that the effects of LT3, DT3 and Ep on erythroid colony
      growth were significantly higher in marrow cultures from anemic rats with CRF,
      indicating an increased proliferative cell kinetics of committed erythroid cells
      in response to these drugs.

PMID- 8580526
TI  - [Biochemical-histological study of the effects of lithium on various organs of
      vizcacha (Lagostomus maximus maximus)].
AB  - Considering that the vizcacha (Lagostomus maximus maximus) is a very Lithium
      sensitive rodent, we planned a biochemical-histological study injecting IP doses
      of 1 mEq/kg/day LiCl during one month to adult vizcachas, and they were divided
      into three lots: Lot I the optical microscopy revealed evident renal, gonadal,
      hyphophyseal and adrenal damages; the biochemical analysis showed that Li
      significantly decreased the female serum LH levels while testosterone and
      estradiol levels were not affected. The male Li serum values resulted to be
      significantly higher than those of female animals. The damage was greater in male
      specimens. Lott II: the tissue recovery from the damage observed in Lot I was the
      following: total in hyphophysis, partial in testis, the same in kidney and was
      enhanced in adrenal and ovary. The Li renal clearance was determined in Lot III
      verifying no changes in both sexs. According to our results, Li (1 mEq/kg/day
      during one month) produce modifications in different tissues probably the gonadal
      damage may be consequence of a direct Li effect and not for a hyphophysis
      alteration, since in male vizcacha the LH serum level was not changed. In regard
      to the selective effect in the suprarenal glomerulus structure, this Li effect is
      produced via hyphophysis. In conclusion, the selective effect of Li on adrenal
      and gonada organs of this rodent is a contribution in order to warm about the
      possible reproduction of such effects in human beings.

PMID- 8580527
TI  - Murine splenic proliferative response to human recombinant erythropoietin along
      hypoxia.
AB  - Hypoxia is the best physiological stress to disturb the erythropoietic steady
      state. The present study has been undertaken in the aim to analize the splenic
      erythropoietic proliferative response with different doses of recombinant human
      erythropoietin under hypoxic conditions along 18 days using the DNA synthesis
      assay. Normoxic splenic progenitors failed to show significative erythroid
      replication at 0 days. A clearly rh Epo response was noticed from 2 to 8 days of
      hypoxia. Splenic proliferation returned to basal pattern from 10 days to the end
      of the experience. The highest proliferative activity, 25 fold increase over
      control (p < 0.001), was found at 6 days from 62.5 to 250 mU/ml rh Epo. These
      results support suggestions that hypoxia induces a transiently erythroid splenic
      proliferative response changing its quantitative parameters in the Epo dose
      response relationship during the physiological adaptation.

PMID- 8580528
TI  - Function and significance of the renal DOPA/DA system.

PMID- 8580529
TI  - Effects of moderate chronic alcoholism treatment on fertilization.
AB  - The effect of 10% m/v ethanol treatment during 4 weeks on mice reproductive
      function was studied. Fertilization rates significantly decreased when oocytes
      came from alcoholic females. Oocytes viability were decreased since fragmented
      ova were increased. Also decreased number of oocytes per oviduct was found.
      Spontaneous activation was increased in alcoholic females. Motility and
      hyperactivation were not been altered by treatment. These results show that the
      female gamete seem to be more sensible to moderate chronic alcoholism than the
      male gamete.

PMID- 8580530
TI  - Indomethacin, esculetin and nordihydroguaiaretic acid modify arachidonate
      biosynthesis in rat adrenocortical cells.
AB  - We have studied the duration of the ACTH inhibition effect on the incorporation
      and transformation of [1-14 C] eicosatrienoic acid, in isolated adrenocortical
      cells of normal rats. The effect of esculetin, indomethacin and
      nordihydroguaiaretic acid alone, or in the presence of ACTH or diBucAMP on
      arachidonate biosynthesis was also investigated. ACTH and diBucAMP produced a
      significant inhibition in arachidonic acid biosynthesis. The inhibition produced
      by ACTH on delta 5 desaturating activity was considered to be a short-term
      effect. Nordihydroguaiaretic acid and esculetin provoked a depression in the
      uptake of 20:3 (n-6) acid and an inhibition in the formation of 20:4 (n-6) acid
      by adrenocortical cells. This effect was potentiated when the cells were
      currently treated with either ACTH or diBucAMP. Indomethacin produced no changes
      in the uptake of 20:3 (n-6) acid, while induced an increment on delta 5
      desaturation activity. This effect would indicate that, normally, the metabolites
      produced by the cyclooxygenase pathway would operate by depressing arachidonic
      acid biosynthesis. Considering the negative regulation of the delta 5 desaturase
      activity system produced by ACTH through cAMP, and the positive modulation
      inferred by the results obtained in this work, it is possible to assume that
      there are, at least, two mechanisms that take place on 20:4 (n-6) acid formation.
      These mechanisms seem to work independently from one another and they probably
      interact when effecting a bi-directional control.

PMID- 8580531
TI  - Opposite effects of interleukin-2 (IL-2) and interferon gamma (IFN gamma) on rat
      atria contractility.
AB  - We have recently shown that interleukin 2 (IL-2) can increase the contractile
      strength or rat atrial muscle through the activation of phospholipases and
      protein kinase C. The results of this study confirm that the reaction of IL-2
      with rat atria involves protein kinase C and not the Ca(++)-calmodulin dependent
      kinases. Phorbol 12-myristate 13-acetate (PMA), a tumor promoter that activates
      protein kinase C directly (bypassing the phosphoinositide turnover step), has
      effects that are similar to those of IL-2 on atrial contractility. Furthermore,
      preincubation of the tissue with PMA prevents the IL-2 effect, suggesting that
      the kinases activated by the tumor promoter and IL-2 share a common substrate.
      This effect of IL-2 on atrial contractility opposes the cholinomimetic inhibitory
      action of IFN gamma. Thus, preincubation of cardiac tissue with IL-2 or PMA
      eliminates the effects of IFN gamma and viceversa. Apparently, the inhibitory
      action of IL-2 on IFN gamma involves an impaired response or atria to cholinergic
      activation, as IL-2 shifts to the right the dose response curve of the tissue to
      the cholinergic muscarinic agonist carbachol. Protein kinase C is also necessary
      for the occurrence of the IL-2-IFN gamma interference. The results of this study
      suggest that, during an inflammatory reaction in the heart, the balance of the
      two lymphokines can determine changes in the response of the tissue to autonomous
      nervous system agonists or to the cytokines that mimic the effects of these
      neurotransmitters.

PMID- 8580532
TI  - Effect of mercuric chloride on the activities of some hepatic enzymes of
      regenerating rabbit liver following partial hepatectomy.
AB  - Mercuric chloride (HgCl2) administered at a dose of 1mg/kg body wt/day for 5 days
      decreased hepatic lactate dehydrogenase (LDH) activity (63%) and increased
      isocitrate dehydrogenase (ICDH) activity (127%). After withdrawal of HgCl2
      treatment for 10 days, the LDH and glutamate pyruvate transaminase (GPT)
      activities showed 56% and 40% decrease, respectively, while alkaline phosphatase
      (AkP) activity increased 4.12 fold. The ICDH activity got normalized. Glutamate
      oxaloacetate transaminase (GDT) was not affected at all. The hepatic LDH, ICDH
      and GPT activities decreased 58%, 72% and 82%, respectively, five days after
      partial hepatectomy (PH), while AkP activity increased 90%. At the end of 15 days
      after PH, the hepatic ICDH activity increased 4.27 fold, while GPT and GOT
      activities decreased 67% and 91%, respectively. The hepatic ICDH activity of PH
      rabbit increased 53%, after 5 days of HgCl2 treatment post-PH, while GPT and AkP
      activities decreased 89% and 97%, respectively, during this period. The ICDH
      activity increased 416%, 10 days after the last dose, while all other enzymes
      showed normal values. The total body growth rate and relative liver weight
      decreased under all experimental conditions.

PMID- 8580533
TI  - Secretion of gelatinases by human pancreatic cancer cell lines: lack of
      correlation with invasive ability.
AB  - Twelve immortalized human cell lines derived from primary or metastatic lesions
      from pancreatic carcinomas were studied with respect to their in vitro
      invasiveness and motility. Various levels of invasive capacity and chemotactic
      responses were found. Zymograms of cells conditioned media were carried out to
      determine the role of metalloproteinases in pancreatic cancer invasion. No
      correlations were found, however, between invasive capacity of pancreatic
      carcinoma cell lines and gelatinase secretion. Putative reasons for these
      findings are discussed.

PMID- 8580534
TI  - Torsional properties of healed canine diaphyseal defects grafted with a fibrillar
      collagen and hydroxyapatite/tricalcium phosphate composite.
AB  - The need for alternatives to autogenous bone grafts is widely recognized. This
      study compared the torsional strength of canine femora 1 year after grafting with
      one of three forms of a collagen/hydroxyapatite/tricalcium phosphate bone
      grafting material (COLLAGRAFTTM), autogenous bone, or no graft. The groups were
      compared to each other and to the unoperated contralateral femora. Results of
      torsional testing were evaluated for torsional strength, torsional displacement,
      total energy to fracture and White fracture mode. Data analysis showed lower
      torsional strength of the operated vs. unoperated femora with the exception of
      morsellized COLLAGRAFTTM material, which had higher strength. However, the only
      difference in the operated groups was that the morsellized COLLAGRAFTTM had
      greater strength than several groups including the autogenous bone group. There
      was no difference found in angular displacement between any of the groups.
      However, there was a difference in the energy to fracture in both strip forms of
      the COLLAGRAFTTM. The final conclusion is that in this model, grafting with
      COLLAGRAFTTM provided torsional properties at one year postoperatively at least
      equivalent to autogenous bone.

PMID- 8580535
TI  - Mixed mode fracture characterization of hydroxylapatite-titanium alloy interface.
AB  - Cantilever beam and four-point bend specimen geometries were used to
      experimentally determine the critical energy release rates for a plasma sprayed
      hydroxylapatite-titanium alloy (HA-Ti alloy) interface. A locus of energy release
      rates as a function of crack tip phase angle was determined where a 0 degree
      phase angle represented tensile opening (mode I) loading and a 90 degree phase
      angle represented in-plane shear (mode II) loading. Energy release rates were
      found to increase substantially with an increase in phase angle. An energy
      release rate of 0.108 N/mm was determined for a phase angle of 0 degrees (mode
      I). Energy release rates of 0.221, 0.686, and 1.212 N/mm were determined for
      phase angles of 66 degrees, 69 degrees, and 72 degrees, respectively. The
      experimental data was matched to a phenomenological model for which crack
      propagation depended on mode I loading alone indicating that crack propagation at
      the Ha-Ti alloy interface is dominated by the mode I loading component.
      Therefore, regions of HA coated implants that experience compressive or shear
      loading across the HA-Ti alloy interface may be much less likely to debond than
      regions that experience tensile loading.

PMID- 8580536
TI  - Load transfer through a hydroxyapatite-coated canine hip implant.
AB  - Strain transfer near hydroxyapatite (HA) coated canine hip implants was examined
      using simulated anatomical loading based on in vivo strain measurements. Strain
      changes near implants relative to intact control values were in excess of 100%
      for transverse and principal strains for zero time period (immediate postimplant)
      specimens. They were generally smaller (100% or less) for axial, transverse, and
      principal minimums in the same locations for 4 months postimplantation specimens.
      Cortical bone loss occurred in all implanted femora. The most extensive loss, up
      to 47%, occurred adjacent to the proximal section of the implant. Extensive
      trabecular bone formation, over 300% in some regions of each femur, was noted in
      all implanted femora. Backscattered electron imaging along the HA-coated sections
      of the implants showed extensive bone bonded to the coating. NOrmal light and UV
      light micrographs showed direct bone apposition to the implant surfaces and
      extensive bone formation in all test animals. Microscopy revealed no evidence of
      any soft tissue layer between the implant and bone. Bone was typically found in
      direct contact with the implant surface. Histomorphometry indicated that bone
      formation rates in the implanted femora were elevated, up to 850%, relative to
      controls. Fewer formation sites were noted on the posterior and lateral (in two
      cases zero sites). Mineral apposition rates (MAR) from two of the dogs were
      slightly elevated (from 110-113%) in the implanted femora relative to controls
      and depressed (to about 83% of controls) in a third.

PMID- 8580537
TI  - Mechanical properties of vacuum-mixed acrylic bone cement.
AB  - The thrust of the present work was the experimental determination of the uniaxial
      static compressive and fully reversed tension-compression fatigue properties of
      CMW 3 acrylic bone cement whose constituents were mixed in a proprietary chamber
      while simultaneously subjected to a vacuum. Selected indices of performance in
      this material are: mean static compressive strength, 81.4 MPa; mean compressive
      modulus of elasticity, 1.95 GPa; endurance limit, 8.1 MPa; and characteristic
      fatigue life (using a three-parameter Weibull fit to the fatigue test data
      obtained at a stress of +/- 10 MPa), 238,712 cycles. The difficulties in
      comparing results obtained using different cement formulations, preparation
      conditions, and test conditions are detailed. With this in mind, it is suggested
      that the present results are within the range of values reported by previous
      workers for other formulations mixed using a variety of methods. The clinical
      significance of the present results is discussed.

PMID- 8580538
TI  - Use of a compact sandwich specimen to evaluate fracture toughness and interfacial
      bonding of bone.
AB  - The objective of the present study was to develop a reliable and statistically
      valid test to measure the fracture toughness of small specimens of bone, and by
      extension, prosthetic materials, using a compact sandwich specimen. Samples of
      bone were sandwiched between holders of a different material and using this
      specimen configuration a new technique was developed to test the fracture
      toughness of the bone interlayer. The effects of different specimens sizes and
      holder materials were investigated empirically. Using finite element analysis a
      correction factor was determined to account for the finite thickness of the
      interlayer and the analytical solutions governing the test specimen were
      accordingly modified. Bulk compact tension specimens of bone were tested for
      comparison. Both wet and dry bone were evaluated and the fracture surface
      morphology characterized using scanning electron microscopy. The results indicate
      no statistically significant differences between the fracture toughness values
      obtained from the compact tension and sandwich specimens. The application of this
      technique to the testing of interfacial bonding between bone and biomaterials is
      discussed.

PMID- 8580539
TI  - Ciprofloxacin attachment to porous-coated titanium surfaces.
AB  - A simple and effective method for attaching ciprofloxacin HCl salt to the surface
      of porous-coated titanium based orthopedic materials was developed. The method
      utilizes the electrophoretic migration of both fine ciprofloxacin HCl particles
      and ciprofloxacin ions to deposit the antibiotic salt on a positively biased
      surface. The quantity of antibiotic deposited can be easily and effectively
      controlled by varying the time of deposition and applied voltage. In vitro tests
      have indicated that the antimicrobial activity of the treated surfaces is
      retained for a period of 5 days. The method allows a significant amount of
      antibiotic to be deposited and could theoretically be used to deliver antibiotics
      to the tissues surrounding prosthetic devices in order to prevent postoperative
      infections.

PMID- 8580540
TI  - Compressive stress relaxation behavior of irradiated ultra-high molecular weight
      polyethylene at 37 degrees C.
AB  - The preconditioned stress relaxation behavior of irradiated ultra-high molecular
      weight polyethylene (UHMWPE), a commonly used bearing surface in total joint
      replacements (TJR), was modelled in uniaxial compression at 37 degrees C. Twenty
      cylindrical specimens (10 mm dia. x 27 mm length) were machined from a
      compression molded plate of medical grade UHMWPE and gamma-irradiated to a
      minimum dose of 2.5 Mrad. At an initial strain rate 1000%/s, five specimens were
      each tested at constant strains of 1, 2, 5, and 10%. The modified superposition
      principle provided a good agreement of the nonlinear viscoelastic (stress
      relaxation) behavior of UHMWPE (standard error of 0.0753 MPa).

PMID- 8580541
TI  - Apatite coated on organic polymers by biomimetic process: improvement in its
      adhesion to substrate by NaOH treatment.
AB  - A dense, uniform and highly biologically active bone-like apatite layer can be
      formed in arbitrary thickness on any kind and shape of solid substrate surface by
      the following biomimetic method at ordinary temperature and pressure. First, a
      substrate is set in contact with particles of bioactive CaO SiO2 based glass
      soaked in a simulated body fluid (SBF) with inorganic ion concentrations nearly
      equal to those of human blood plasma. Second, the substrate is soaked in another
      solution with ion concentrations 1.5 times those of SBF (1.5 SBF). In the present
      study, organic polymer substrates treated with 5 M NaOH solution were subjected
      to the above mentioned biomimetic process. The induction periods for the apatite
      nucleation on polyethyleneterephthalate (PET), polymethylmethacrylate (PMMA),
      polyamide 6 (PA6), and polyethersulfone (PESF) substrates were reduced from 24 to
      12 h with the NaOH treatment. The adhesive strength of the formed apatite layer
      were increased from 3.5 to 8.6 MPa, from 1.1 to 3.4 MPa, and from 0.6 to 5.3 MPa
      with the NaOH treatment, for PET, PMMA, and PA 6, respectively. It was assumed
      that highly polar groups, such as carboxyl and sulfinyl ones formed by the
      hydrolysis of an ester group on PET and PMMA and of an amide group on PA 6, or of
      a sulfonyl group on PESF with the NaOH treatment, attached a large number of
      hydrated silica dissolved from the glass particles, to accelerate the apatite
      nucleation, and also to form a strong bond with the apatite. The apatite-organic
      polymer composites thus obtained are expected to be useful as bone-repairing as
      well as soft tissue-repairing materials.

PMID- 8580542
TI  - Effects of fixation technique on displacement incompatibilities at the bone
      implant interface in cementless total knee replacement in a canine model.
AB  - Bone-implant displacements can be caused by rigid body motion and by differences
      in material properties of the implant and bone. In the present study of the
      tibial component in total knee replacement, we tested a series of tibial
      component fixation designs to determine how certain design features influenced
      the magnitude of the tangential displacement between the component and supporting
      bone in a canine model. The transverse expansion of the proximal tibia under
      static axial loading was measured in the intact tibia and then in the same bone
      following implantation of tibial components with different interface
      characteristics: cementless flat smooth, cementless flat porous-coated,
      cementless flat porous-coated with screws, cementless pegged porous-coated,
      cementless pegged porous-coated with screws, cemented pegged, and cemented pegged
      with screws. In all cases, the magnitude of the transverse expansion increased
      with higher applied loads. When the statistical analysis was restricted to the
      cementless interfaces, the presence/absence of the porous coating, the
      presence/absence of pegs, and the use of screws had no significant influence on
      tibial expansion. However, in an analysis including the cemented and cementless
      pegged components, tibial expansion was reduced with the use of screws. The
      magnitude of the interface motion due to these displacement incompatibilities was
      approximately fivefold lower than the amount of interface motion related to rigid
      body motion found in a separate study with the canine model. The measured
      expansion was similar in the intact tibiae and the implanted tibiae, suggesting
      that the transverse constraint in the canine proximal tibia must be provided by
      the surrounding cortical ring rather than the subchondral bone.

PMID- 8580544
TI  - Improved sensitivity and decreased sample size in a cytotoxicity test for
      biomaterials: a modified colony microassay using a microplate and crystal violet
      staining.
AB  - Modified Eagle's minimum essential medium supplemented with 5% fetal calf serum
      was highly sensitive to cytotoxicity and formed large control colonies in the V79
      colony assay. A highly sensitive cytotoxicity test was developed using 96-well
      microtiter plates. Test chemicals or extracts of polyurethane materials
      containing the same chemicals were added 24 h after inoculation of cell
      suspensions. The cells were fixed and stained with crystal violet after
      additional culture for 6 days (V79 cells) or 10 days (Balb/3T3 cells). In terms
      of sensitivity and rapid quantitative measurement, this modified colony
      microassay, using a low cell density in 96-well microplates, was superior to
      various cytotoxicity tests such as colony, growth inhibition, cytolethality, and
      agar diffusion assays.

PMID- 8580543
TI  - Adsorption of collagenase to particulate titanium: a possible mechanism for
      collagenase localization in periprosthetic tissue.
AB  - Osteolysis is a central feature of aseptic loosening of orthopaedic joint
      prostheses. This destructive process is believed to result from phagocytosis of
      implant wear debris by periprosthetic and synovial macrophages and the subsequent
      release of proinflammatory mediators, including collagenase. Isolated murine
      macrophages were cultured in vitro with particulate titanium in order to explore
      the mechanism of macrophage activation by particulate wear debris. The results,
      in which the amount of secreted, soluble collagenase in culture supernatants was
      inversely proportional to titanium concentration, suggested that titanium
      strongly adsorbed secreted collagenase. This inference was confirmed by direct
      binding assays in which particulate titanium coated with adsorbed collagenase
      bound an alkaline phosphatase conjugated anti-collagenase antibody, but not a
      conjugated anti-IgG antibody. Adsorption of collagenase was not influenced by
      preincubation of titanium particles with albumin. The adsorbed collagenase
      remained enzymatically active as indicated by its ability to hydrolyze a
      synthetic peptide substrate. These results demonstrate that particulate titanium
      stimulates collagenase production by macrophages and then strongly adsorbs the
      secreted proinflammatory enzyme. The process of macrophage stimulation,
      collagenase secretion, and adsorption may represent an important mechanism for
      localization and concentration of collagenase in periprosthetic and synovial
      tissue, a mechanism that ultimately triggers bone resorption through osteoclast
      activation.

PMID- 8580545
TI  - A new saw technique improves preparation of bone sections for light and electron
      microscopy.
AB  - A newly developed saw technique was developed to produce sections circa 10
      microns or thicker from fresh bone or dentine and from plastic embedded
      undecalcified bone tissue with or without implant materials. The method comprises
      only one step because grinding or polishing to make the sections thinner is not
      necessary. The bone slices can be decalcified rapidly without using aggressive
      solvents and used for making ultrathin sections for electron microscopy. Sections
      of fresh dentine of 15 to 30 microns are transparent which makes it possible to
      study osteoclastic resorption in vitro. Sections, 10 microns thick, with an
      intact interface of bone and implant material can be observed for
      biocompatibility studies.

PMID- 8580546
TI  - Substantially equivalent to what?

PMID- 8580547
TI  - Biomaterials applicability: establishing suitable "materials' equivalency"
      protocols.

PMID- 8580548
TI  - Sarcoidosis: changing clinical manifestation in Japan.

PMID- 8580549
TI  - Myelodysplastic syndromes with monosomy 7 and granulocyte colony-stimulating
      factor.

PMID- 8580550
TI  - Systemic calciphylaxis.

PMID- 8580551
TI  - Amyotrophic lateral sclerosis.
AB  - The final cascade of amyotrophic lateral sclerosis (ALS) coincides with the onset
      of clinical neurological deficits and involves multifactorial interactive
      mechanisms. These terminal events include excitotoxicity, free radical
      accumulation and possibly immunological disturbances. They are probably predated
      by months or years by thus far unidentified triggers. Selective vulnerability of
      the corticomotneuronal system in ALS is likely due to degradation of several gene
      products essential to transmitter, receptor and nerve growth factor maintenance
      specific to this functional system. Therapeutic strategies involve
      neuroprotection, symptomatic and combination neuronal therapy targeted to the
      final cascade of ALS.

PMID- 8580552
TI  - Pulmonary sarcoidosis: pathogenesis and population differences.
AB  - Sarcoidosis is a systemic disease. Clinical manifestations and prognosis are
      heterogeneous in sarcoidosis patients from various populations. This suggests
      that genetic factors and/or environmental factors seem to play important roles in
      the pathogenesis. Sarcoidosis is characterized as a hyperimmune response to
      unknown agent(s) at the lesion sites. Regarding pulmonary lesions, macrophage-T
      lymphocyte alveolitis precedes epithelioid cell granuloma formation. In this
      review, reports presented in international meetings were introduced to compare
      population differences; we attempted to review the issues which relate to disease
      susceptibility in patients with sarcoidosis. In addition, we discussed the
      possible causative agents, whether T cell receptor expression reflects antigen
      driven immune responses, and what type of biological active materials may be
      critical in determining the disease activity and/or prognostic factors, with
      particular focus on the population differences.

PMID- 8580553
TI  - Herpes simplex virus type 2 infections presenting as brainstem encephalitis and
      recurrent myelitis.
AB  - We describe here 3 patients with central nervous system infection caused by
      herpes simplex virus type 2 (HSV-2); one patient with brainstem encephalitis and
      two with recurrent transverse thoracic myelitis. All three patients showed
      increased IgG antibodies to HSV in the cerebrospinal fluid (CSF). HSV-2 DNA was
      demonstrated in the CSF by polymerase chain reaction (PCR) amplification. Upon
      treatment with acyclovir, one patient with myelitis partially recovered and the
      others completely recovered. It is important to recognize the wide spectrum of
      clinical manifestations of HSV-2 infection in the central nervous system (CNS).

PMID- 8580554
TI  - Hereditary non-progressive torsion dystonia with intellectual disturbance.
AB  - Three siblings of a consanguineous parents with involuntary movements are
      reported. The mother had only a very slight neck tremor, without any other
      neurological abnormality, and the father had died. The 38-year-old son (Case 1)
      complained of involuntary movements at the age of 6. His involuntary movements
      were observed in the tongue, perioral region and upper and lower extremities:
      jerky movements with dystonic features. The 46-year-old elder brother (Case 2)
      experienced involuntary movements at the age of 18. Involuntary movements were
      observed in the upper extremities; he also had torticollis and tremulous
      movements in the neck, and jerky movements in the perioral region. They showed
      gait disturbance and dysarthria. The 35-year-old sister (Case 3) also experienced
      involuntary movements. When she was writing, her involuntary movements were
      obvious: dystonia and myoclonic jerks. Tremor in the neck was also seen. Their
      intelligence was below average. We concluded that this family had hereditary
      torsion dystonia, with myoclonus, and low intelligence. This condition may be
      associated with an autosomal recessive gene.

PMID- 8580555
TI  - Characterization of distribution of T lymphocyte subsets and activated T
      lymphocytes infiltrating into sarcoid lesions.
AB  - We studied the relationship between various T lymphocyte functions and granuloma
      formation in 5 lung tissue and 4 lymph node tissue samples from patients with
      sarcoidosis by immunohistological methods. In the lesion of sarcoidosis, T cells
      were positive for alpha beta TCR, but gamma delta TCR-positive T cells were
      rarely observed. The results of analysis of functional subsets showed that T
      cells in the internal area of granuloma were predominantly helper/inducer subset
      (CD4+CD45RA-). On the other hand, cytotoxic T cells (CD8+CD45RA-CD11b-) were
      present in abundance in the outer boundaries of granuloma. In addition,
      suppressor-inducer T cells (CD4+CD45RA+) were present in the surrounding areas.
      However, T cells of various subsets were present sporadically outside the
      granulomas. We also studied the distribution of T cells expressing activation
      related antigens. The results showed that T lymphocytes in the internal area of
      granulomas more frequently had these antigens than did T lymphocytes in the
      external area. These findings suggested that T cells infiltrating into the
      sarcoidosis lesion demonstrated a layer-like distribution based on functional
      subsets. These findings also confirm that activated T cells were more abundantly
      distributed in the internal area of sarcoid granuloma than in the external area.

PMID- 8580556
TI  - Comparison of the therapeutic efficacy of continuous and intermittent injection
      of isosorbide dinitrate: a randomized study on unstable angina.
AB  - Therapeutic efficacy of intermittent and continuous injection of isosorbide
      dinitrate (ISDN) was compared in 22 patients (mean age 64 +/- 10, 18 males and 4
      females) with unstable angina at rest. They were randomized into 2 groups that
      received either continuous (10 mg/h, group A) or intermittent (10 mg/10 min every
      2 hours, group B) injection of ISDN for 3 days (phase 1). Each injection protocol
      was switched (phase 2) and subsequently switched back to the initial protocol
      (phase 3) in a cross-over fashion. The serum concentrations of ISDN, 2-isosorbide
      mononitrate (2-ISMN) and 5-ISMN were measured serially during both intermittent
      and continuous injection protocols. In addition, the incidence and duration of
      angina and changes in systolic blood pressure were analyzed. There were 3
      treatment-failure cases during the intermittent injection period and 1 during the
      continuous injection period. Three of these treatment-failure cases developed
      small acute myocardial infarcts despite emergent coronary arteriography followed
      by intra-coronary thrombolysis and percutaneous balloon angioplasty. There was no
      difference in therapeutic efficacy between continuous and intermittent ISDN in
      terms of the incidence, duration of angina attacks and the number of patients
      whose angina was suppressed. After bolus injection of ISDN (10 mg/10 min), the
      serum concentration of ISDN increased rapidly and returned to the control level
      at 60 minutes after the injection. The serum 5-ISMN and 2-ISMN concentrations
      also increased immediately after injection and then decreased gradually reaching
      statistically insignificant level to the control values at 60 minutes after
      injection. With continuous injection, ISDN and its metabolites increased
      gradually and reached similar but slightly lower serum concentrations to the peak
      levels during intermittent injection. We conclude that the therapeutic efficacy
      of intermittent and continuous injection of ISDN is similar in patients with
      unstable angina.

PMID- 8580557
TI  - Leukemia developing after 131I treatment for thyroid cancer in a patient with
      Werner's syndrome: molecular and cytogenetic studies.
AB  - A 40-year-old female patient with Werner's syndrome (WS) suffering from thyroid
      cancer and myelodysplastic syndrome (MDS) is reported. She had been diagnosed as
      having WS complicated with thyroid cancer seven years previously. Total
      thyroidectomy and radioactive iodine (131I, 100 mCi/year) therapy for seven years
      had slowed the progression of thyroid cancer. She suffered a sudden onset of MDS
      at the age of 40 years. After six months she died from overt leukemia. We found
      an additional chromosome aberration of chromosome 10 in the progression of
      leukemia from MDS.

PMID- 8580558
TI  - Severe hypercalcemia and polyuria in a near-drowning victim.
AB  - A 73-year-old man was admitted because of near-drowning in a hot springs bath.
      Transient severe hypercalcemia and polyuria were seen during the first hospital
      day. It seemed that the hypercalcemia was due to acute intoxication from calcium
      contained in the water of the spring absorbed mainly through the alveoli. To our
      knowledge, this is the first case of acute hypercalcemia complicating a near
      drowning in a hot spring. Analysis of serum and urine electrolytes during the
      polyuric phase revealed saline diuresis, which was probably due to interference
      by the hypercalcemia of the reabsorption of sodium and free water.

PMID- 8580559
TI  - Ofloxacin-induced vasculitis.
AB  - We describe a patient with hypersensitivity vasculitis due to ofloxacin therapy;
      the vasculitis was associated with elevated transaminase and IgA levels.
      Cyclophosphamide and intravenous pulse prednisolone resulted in clinical
      improvement.

PMID- 8580560
TI  - Acute myelocytic leukemia relapse with intramedullary spinal cord tumor
      involvement during hematological remission.
AB  - A 64-year-old man who had been diagnosed as having acute myelocytic leukemia (M2
      in the FAB classification) developed central nervous system involvement of
      intramedullary spinal cord during hematological remission. Magnetic resonance
      imaging showed a low signal intensity mass on T1-weighted images and a high
      signal intensity mass on T2-weighted images. The mass was slightly enhanced by
      gadolinium-diethylenetriaminepentaacetic acid. His neurological symptoms were
      slightly improved by intrathecal and systemic chemotherapy combined with external
      irradiation, although the size of the mass did not change.

PMID- 8580561
TI  - Familial hypobetalipoproteinemia associated with hypothyroidism.
AB  - A 55-year-old Japanese woman with familial hypobetalipoproteinemia associated
      with hypothyroidism was admitted to the hospital because of orthopnea and
      congestive heart failure. Thyroid function testing revealed hypothyroidism, but
      she exhibited low levels of serum cholesterol (111 mg/dl) and apolipoprotein
      (apo) B (48.5 mg/dl). No abnormal bands were detected with gradient sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis of very low density
      lipoprotein, low density lipoprotein and high density lipoprotein followed by
      immunoblotting with anti apo B polyclonal antibody. In this case, apo B
      structural abnormality could not be identified.

PMID- 8580562
TI  - Acute gastric mucosal lesions associated with cytomegalovirus infection in a non
      immunocompromised host.
AB  - A 75-year-old woman with epigastric pain and tarry stool was admitted to our
      hospital, where upper gastrointestinal endoscopic study revealed multiple gastric
      ulcers. The endoscopic biopsy specimens obtained on the seventh hospital day
      disclosed a few typical intranuclear cytomegalovirus inclusions. Cytomegalovirus
      DNA was detected using polymerase chain reaction in a biopsy specimen. No
      immunologic abnormalities were demonstrated by any laboratory tests. While only a
      few cases of cytomegalovirus-associated gastric ulcer in non-immunocompromised
      hosts have been reported, this entity may be more frequently detected when
      careful histological examination is performed in the active stage rather than
      postponed until after healing of the ulcer.

PMID- 8580563
TI  - Neuroendocrine tumors of the liver and pancreas associated with elevated serum
      prostatic acid phosphatase.
AB  - A 58-year-old man was revealed to have multiple liver tumors with elevated
      prostatic acid phosphatase (PAP) during a medical examination. The tumors were of
      neuroendocrine nature, but no abnormal findings were obtained in other organs in
      which neuroendocrine tumors develop frequently. Repeated transarterial
      embolization was partially effective. However, the tumors became resistant to the
      therapy three years later, continued growing and ruptured. Autopsy disclosed
      neuroendocrine tumors in the pancreas, which were immunohistologically positive
      for PAP. Neuroendocrine tumors of the pancreas and liver producing PAP are rare;
      this case is reported with a review of literature.

PMID- 8580564
TI  - Evolution of severe aplastic anemia to myelodysplasia with monosomy 7 following
      granulocyte colony-stimulating factor, erythropoietin and high-dose
      methylprednisolone combination therapy.
AB  - A 19-year-old man was diagnosed as having severe aplastic anemia and received
      high-dose methylprednisolone treatment without hematological response. A second
      course of high-dose mPSL treatment together with granulocyte colony-stimulating
      factor (G-CSF) plus erythropoietin (EPO) was then started and resulted in
      trilineage blood cell response. Ten months after the combination therapy
      thrombocytopenia developed and cytogenetic analysis showed 45,XX,-7, indicating
      an evolution to myelodysplastic syndrome (MDS) associated with monosomy 7.G-CSF
      and EPO treatment together with immunosuppression may be an effective therapy in
      SAA patients, but such a therapy may increase the risk of evolution to MDS.

PMID- 8580565
TI  - Calcitonin-like polypeptides without apparent biological activity in a patient
      with recurrent medullary thyroid carcinoma.
AB  - A 51-year-old male with a recurrent medullary thyroid carcinoma (MTC) showed high
      serum levels of calcitonin (CT) and carcinoembryonic antigen (CEA) but with
      concomitant normocalcemia. The CT activities of the patient's serum in vivo
      (hypocalcemic activity in rats) and in vitro (cyclic AMP-increasing activity in
      cultured human mammary tumor, T47D) were much lower than those expected from the
      patient's CT level. High performance liquid chromatography (HPLC) with
      radioimmunoassay (RIA) detection gave a broad spectrum of molecular weights of CT
      like polypeptides in the 3 kDa to 200 kDa range with separation from CEA,
      suggesting that the mechanism for CT production in MTC is an obscure one.

PMID- 8580566
TI  - Acquired factor VIII-specific antibody disorder accompanied by a life-threatening
      retroperitoneal hematoma.
AB  - A male patient, aged 58, without any discernible underlying disease developed a
      massive hemorrhage in the retroperitoneal cavity and in the femoral muscle. The
      hemorrhagic tendency of the patient was found to be due to the acquired anti
      Factor VIII specific autoantibody in the blood. A concentrate of an activated
      prothrombin complex (FEIBA: Factor eight inhibitor bypassing activity) was
      administered and produced a remarkable effect in stemning the bleeding tendency
      of the patient. Immunosuppressive therapy was also effective for the control of
      the bleeding.

PMID- 8580567
TI  - Non-insulin-dependent diabetes mellitus complicated with idiopathic
      hypoparathyroidism.
AB  - We report a case of non-insulin-dependent diabetes mellitus (NIDDM) complicated
      with idiopathic hypoparathyroidism. A 74-year-old male was hospitalized because
      of diplopia. He was revealed to have NIDDM. The levels of serum Ca and intact-PTH
      were 6.3 mg/dl and < 5 pg/ml, respectively. Brain computed tomography revealed
      abnormal calcification in the cerebral basal ganglia and the cerebellum. After
      recovery from hypocalcemia, the endogenous insulin secretion was normalized. It
      is suggested that the pathogenesis of NIDDM in this patient may have been related
      to an insulin secretory defect as a result of hypocalcemia in addition to the
      hereditary risk.

PMID- 8580568
TI  - A dialysis patient with systemic calciphylaxis exhibiting rapidly progressive
      visceral ischemia and acral gangrene.
AB  - Systemic calciphylaxis is a rare, poorly understood syndrome of progressive
      peripheral ischemic necrosis and medial arterial calcification in patients with
      end-stage renal disease. We report a patient with this syndrome which developed
      following corticosteroid administration and who ultimately required amputation of
      the four extremities. Furthermore, cerebral, myocardial, splenic, and intestinal
      infarctions also developed in parallel with the increment of visceral arterial
      calcification. No evidence of noticeable hyperparathyroidism or elevation of
      serum calcium-phosphate product was observed. We speculated that, in addition to
      diabetes mellitus and chronic renal failure while undergoing dialysis therapy,
      the administration of corticosteroids might act synergistically to cause
      calciphylaxis.

PMID- 8580569
TI  - Central diabetes insipidus caused by pituitary metastasis of lung cancer.
AB  - Tumor metastasis to the hypophyseal system has rarely been reported with either
      clinical or radiographic evidence. A 52-year-old woman presented with polydipsia,
      polyuria, and loss of appetite. She was diagnosed as having diabetes insipidus
      caused by pituitary micrometatasis of lung adenocarcinoma. After she had been
      treated with radiation therapy to the pituitary gland, the gland size was reduced
      as confirmed by magnetic resonance imaging, and her urine volume decreased.
      However, meningitis carcinomatosa appeared later. This was a rare case of
      secondary diabetes insipidus due to pituitary metastasis of lung cancer.

PMID- 8580570
TI  - Cardiac involvement in a family with Becker muscular dystrophy.
AB  - We report a family with Becker muscular dystrophy (BMD) presenting with cardiac
      involvement. The proband was a 41-year-old Japanese man who was hospitalized with
      exertional dyspnea and muscle weakness. Cardiac examination showed findings
      consistent with dilated cardiomyopathy. Dystrophin immunohistochemical analysis
      showed a discontinuous patchy staining pattern in cardiac and skeletal muscles
      biopsied from the proband. His brothers had high creatine kinase (CK) activity
      and abnormal electrocardiogram. Dystrophin gene analysis revealed that the
      proband and his brothers had G-to-T transversion at the terminal nucleotide of
      exon13. We conclude that the mutated dystrophin gene may cause cardiac
      involvement as a symptom precedent to skeletal muscle involvement.

PMID- 8580571
TI  - Development of hypercalcemic crisis in a Graves' hyperthyroid patient associated
      with central diabetes insipidus.
AB  - A 26-year-old man with Graves' hyperthyroidism associated with central diabetes
      insipidus (DI), initially showed hypercalcemic crisis. Initially, very low serum
      levels of intact parathyroid hormone (PTH) and 1,25-dihydroxy vitamin D3 and a
      moderate rise of serum C-terminal PTH related protein (C-PTHrP) were observed
      which strongly suggested a humoral hypercalcemia of malignancy due to PTHrP.
      However, the serum C-PTHrP level later became normal. Mild hyperprolactinemia, no
      responses of growth hormone (GH) to insulin-induced hypoglycemia despite a normal
      growth hormone releasing hormone (GRH) test and mild thickening of the pituitary
      stalk on magnetic resonance imaging were observed. Thus, an autoimmune nature of
      his central DI is considered; it is noteworthy that the serum C-PTHrP level may
      be elevated by renal failure in patients with hypercalcemia due to causes other
      than PTHrP.

PMID- 8580572
TI  - Successful treatment of spasmodic torticollis with triazolam.

PMID- 8580573
TI  - Total parenteral nutrition and immune system activity: a review.
AB  - Malnutrition has been associated with immunosuppression, reduced host defenses,
      and increased incidence of infections and mortality. Improvement of nutritional
      status through various nutritional support regimens may restore immunocompetence
      and consequently reduce the rate and severity of infections in hospitalized
      patients. However, several investigators, exploring the effect of total
      parenteral nutrition (TPN) on the immune system, have suggested that TPN may
      adversely affect immune function. During the past 20 yr special interest was
      given to the possible immunosuppressive effect of parenteral fat emulsions and
      conflicting reports have been published. This review focuses on the consequences
      of TPN on immune response and investigates whether there might be a link between
      the nutrients, the immune system, and possibly the central nervous system, which
      also seems to affect immune response.

PMID- 8580574
TI  - Effects of moderate changes in protein intake on urinary albumin excretion in
      type I diabetic patients.
AB  - We investigated the short-term effects of moderate increments or decrements of
      protein intake on albumin excretion rates of type I diabetic patients. Ten
      normotensive patients with either normal albumin excretion rates (< 20
      micrograms/min, group I, n = 5) or persistent mu-albuminuria (20-200
      micrograms/min, group II, n = 5) were fed successively three test diets providing
      different protein intakes. Each patient was randomly allocated to 3-wk sequences
      of the following diets: low-protein diet (LPD; median 0.84, range 0.76-0.94 g.kg
      1.day-1), medium-protein diet (MPD; median 1.33, range 0.98-2.00 g.kg-1.day-1),
      and high-protein diet (HPD; median 2.05, range 1.54-2.61 g.kg-1.day-1). The three
      diets were isoenergetic and isoglucidic. In group I patients, no consistent
      change was found in mu-albuminuria. In group II patients, LPD resulted in a
      reduction in mu-albuminuria compared with MPD and HPD. Changes in albumin
      excretion rates were positively correlated to relative changes in protein intake.
      This suggests that moderately protein-restricted diets can reduce mu-albuminuria
      in diabetic patients suffering from incipient nephropathy, the degree of
      reduction depending on the degree of restriction. Because of poor patient
      compliance with protein intakes < 0.8 g.kg-1.day-1, we conclude that moderately
      rather than severely protein-restricted diets should be recommended for long-term
      prescriptions.

PMID- 8580575
TI  - Nutritional growth retardation is associated with defective lung growth in cystic
      fibrosis: a preventable determinant of progressive pulmonary dysfunction.
AB  - Evidence for a relationship between nutritional growth retardation in cystic
      fibrosis (CF) and progressive pulmonary dysfunction was evaluated by a
      prospective longitudinal study of changes in nutritional growth parameters, in
      relation to changes in pulmonary function data, in 61 moderately affected CF
      patients, aged 5-17 yr, during the equilibrated phase of lung growth. Age, sex,
      initial and serial weight and height Z scores, body cell mass (BCM) by total-body
      potassium (TBK) analysis, and changes in forced expiratory volume in 1 s (FEV1)
      and forced vital capacity (FVC), excluding data during pulmonary exacerbations,
      were analyzed by multiple regression analyses. The only significant predictor of
      change in FVC (best-fit model) was change in BCM, expressed as TBK (g/yr), TBK
      for age (percentage predicted), and TBK for height (percentage predicted) (p <
      0.01). Standard anthropometric variables were not predictive. No reliable
      predictive model emerged for changes in FEV1. Relative decline in TBK for age was
      strongly predictive of decline in FVC (percentage predicted) accounting for 23%
      of this change. Patients with normal growth of the BCM had significantly less
      decline in FVC than those with retarded growth of the BCM (a fall of 2.5 vs.
      6.8%/yr, p < 0.01). Impaired growth of the metabolically active BCM appears to be
      associated with progressive lung dysfunction in CF, possibly mediated by impaired
      lung growth. Achieving optimal nutrition and growth may minimize the progressive
      decline in pulmonary function commonly seen in this disease.

PMID- 8580576
TI  - Tentative diet for liver failure containing well-polished rice.
AB  - A liver-failure diet (low in protein) that contained rice polished to 50% to
      reduce the protein content of the diet was given to patients with uncompensated
      liver cirrhosis and compared with a standard liver-failure diet containing
      conventionally processed rice. The amount of boiled rice served in each meal
      could be increased by using well-polished rice and the use of supplementary
      sources of energy (powdered starch syrup, jelly, cookies, and candy sugar) was
      unnecessary. In the liver-failure diet containing well-polished rice, the
      methionine contents could be reduced and the Fischer ratio could be increased.
      The ingestion rate of the diet with well-polished rice was 80% and the diet was
      rated favorably in a questionnaire on palatability. Decreases in blood ammonia
      concentrations were observed in three patients given the liver-failure diet with
      well-polished rice for 2 wk by the crossover method.

PMID- 8580578
TI  - Effect of lipid emulsions for total parenteral nutrition on regeneration of the
      liver after partial hepatectomy in rats.
AB  - We studied the effects of lipid emulsions for total parenteral nutrition (TPN) on
      hepatic regeneration after partial hepatectomy in rats. Daily energy intake was
      maintained at 1172 kJ.kg-1.day-1 while the percentage of nonprotein energy
      sources was changed. Animals were divided into four groups: lipid-free, 10%
      lipid, 20%-lipid, and 40%-lipid. TPN was continued for up to 1 wk. The content of
      proteins, the ratio of proteins to triglycerides, and the yield of mitochondrial
      protein in the remnant liver 7 days after partial hepatectomy were larger in
      animals receiving TPN with lipids than in those receiving lipid-free TPN, whereas
      the amounts of triglycerides and cholesterol in the liver of the latter animals
      were larger. The degree of fatty infiltration of the hepatic lobule was most
      distinct in the lipid-free group. Furthermore, activities of glutamic oxaloacetic
      transaminase, glutamic pyruvic transaminase, and alkaline phosphatase in the
      serum tended to be higher in the lipid-free group. Phosphorylating ability of
      mitochondria in the regenerating liver 7 days after partial hepatectomy was not
      different among the four groups; however, the highest value for the respiratory
      control index was obtained in the 40%-lipid group. The application of a lipid
      emulsion to TPN is useful for hepatic regeneration after partial hepatectomy;
      however, the ideal concentration of lipids in TPN awaits further investigation.

PMID- 8580577
TI  - Randomized trial of tolerance and efficacy of a small-peptide enteral feeding
      formula versus a whole-protein formula.
AB  - Enteral feeding with formulas containing proteins as small peptides may be better
      tolerated and more efficacious than whole-protein diets, particularly in
      critically ill patients. We stratified patients beginning enteral feeding
      according to treatment with antibiotics or not and serum albumin level (< or = 25
      or > 25 g/L) and randomly assigned them to treatment with a small-peptide enteral
      diet or a whole-protein diet. All causes of diarrhea were ascertained (defined as
      > 200 g stool or > or = three liquid stools on 2 consecutive days). The study was
      considered complete when diarrhea occurred, or when substantial feeding had been
      administered without diarrhea for > or = 5 days. Most of the 41 subjects who
      completed the trial were critically ill. Eight subjects experienced diarrhea
      (20%), which was caused by tube feeding in six patients (four consuming the small
      peptide diet and two consuming the whole-protein diet) and by other factors in
      two (one on each regimen). Diarrhea was not associated with serum albumin,
      treatment with antibiotics, or critical illness. There were no differences
      between treatment groups regarding changes in serum prealbumin or fibronectin.
      During 5 days of feeding, a small-peptide diet and a whole-protein diet produce
      similar rates of diarrhea and similar changes in serum proteins.

PMID- 8580580
TI  - A case of overfeeding complicating the management of adult respiratory distress
      syndrome.

PMID- 8580579
TI  - Arginine-supplemented diets inhibit endotoxin-induced bacterial translocation in
      mice.
AB  - We studied the effects of supplemental dietary arginine (ARG) on endotoxin
      induced bacterial translocation. Mice were fed a 20%-casein diet (control) or a
      20%-casein diet supplemented with 2% or 4% ARG and then injected with
      lipopolysaccharide (1 mg/500 microliters). The incidence of bacterial
      translocation was noted by the recovery of viable organisms from the mesenteric
      lymph node (MLN) and spleen. The mortality rates of the mice were 40%, 10%, and
      20% in the control group and 2%- and 4%-ARG groups, respectively. Of the
      surviving mice, bacterial translocation occurred in 100% of the control group, in
      56% (MLN) and 56% (spleen) in the 2%-ARG group, and in 36% (MLN) and 25% (spleen)
      in the 4%-ARG group. Quantitative colony counts and median numbers of viable
      bacteria were lower (p < 0.05) in the 2%-ARG group and slightly lower in the 4%
      ARG group compared with the control group. MLN and spleen weights expressed as a
      percentage of body weight were heavier (p < 0.05) only in the 2%-ARG group. These
      results support the concept that bacteria may translocate from the gut to other
      organs and be a potential source of lethal infection after injury, and that
      supplementation with 2% or 4% ARG could improve outcome.

PMID- 8580581
TI  - Nutrition, lysosomal proteases, and protein breakdown.
AB  - We review the role played by the lysosomal proteases on cellular protein
      breakdown and their relation to nutrition research. Several recent works have
      shown that an important group of lysosomal proteases (cathepsins) are directly
      responsible for the maintenance of protein breakdown. The determination of their
      enzyme activity or measurement of mRNAs as an index of gene expression have
      provided new views about the mechanisms of protein-breakdown regulation. The
      introduction of molecular biology could provide new ways with which to manipulate
      the catabolic response of injured patients.

PMID- 8580582
TI  - Nutritional effect of continuous hemodiafiltration.
AB  - Continuous arterial-venous and veno-venous hemodiafiltration are reliable methods
      of renal replacement therapy and are particularly suited to critically ill
      patients in acute renal failure. Fluid and uremic toxin removal from continuous
      hemodiafiltration is sufficient to allow unrestricted nutrition support. However,
      the hemodiafilter cannot discriminate between uremic toxins and nutrients.
      Therefore, the potential exists for significant nutrient loss during continuous
      hemodiafiltration. Amino acid loss during continuous hemodiafiltration is
      approximately 10-15 g/day, although in individual cases > or = 30 g/day can be
      lost. Neither lipids nor intact proteins are lost to any appreciable degree
      during continuous hemodiafiltration. Small amounts of glucose are lost if
      dextrose-free dialysate is used for dialysis. If dextrose-containing dialysate is
      used, significant amounts of glucose can be absorbed (35-45% of the infused
      glucose). Fluid replacement with dextrose-containing electrolyte solutions can
      also lead to significant infusion of glucose. Vitamin and mineral losses during
      continuous hemodiafiltration are not known; neither are the vitamin requirements
      for patients receiving continuous hemodiafiltration. Effects of continuous
      hemodiafiltration on vitamin and mineral loss and status remain an important
      research question.

PMID- 8580583
TI  - Nutrition, immunology, neuroscience, and behavior.

PMID- 8580585
TI  - Understanding the pathological mechanisms underlying protein breakdown for new
      therapeutic strategies.

PMID- 8580584
TI  - Do peptide-based enteral formulas provide any benefit over intact protein diets?

PMID- 8580587
TI  - Hypothalamic regulation of energy balance and feeding behavior. 1974.

PMID- 8580586
TI  - Polyphenols in our diet: do they matter?

PMID- 8580588
TI  - [Partial financing of public health services by federal insurance--conceptional
      restriction or future model?].
AB  - The growing deficits of community budgets force the Public Health Service to
      streamline its duties and activities and to develop strategies which allow
      reimbursement by other resources. The possibilities for part financing of tasks
      of the Bremen Public Health Office by local statutory health insurance funds are
      considered and discussed.

PMID- 8580589
TI  - [Strained relations between federal health insurance and the public health
      service].
AB  - A close cooperation between all partners according to section 20 IV SGB V is
      basically welcome. However, in times of financial straits in public budgets,
      attempts have to be avoided to shift tasks and financial burdens to statutory
      health insurance (SHI). A series of examples shows that because of the different
      responsibilities-related to the insured persons on the one hand, and the general
      population on the other-tendencies to shift burdens to SHI are observed. However,
      such measures are neither adequate nor without problems (e.g. protection by
      vaccination). Public health service is requested to improve its epidemiological
      capacities and the qualification of its doctors. Furthermore, the service should
      be re-orient to a modern citizen-oriented service organization. Communities and
      provincial ("Land") governments have to provide the financial prerequisites.

PMID- 8580590
TI  - [Cooperation between the public health office and federal health insurance in the
      area of health promotion].
AB  - During the last few years several health projects were realised in cooperation
      with health insurance societies. One of the projects concerned the sports
      possibilities for people suffering from chronic diseases. Another one supplied
      information on symptoms of cardiac infarction. Cholesterol levels were analysed,
      height an body weight were determined and blood pressure was measured.
      Additionally, several data on anamnesis were stored anonymously as data files.
      One of the projects was performed with a normal part of the population in the
      office of a bank. During this arrangement many young people were also examined.
      Another event was a "doctor-patient-seminar" on the subject of cardiac
      infarction. We wanted to demonstrate a few interesting differences between the
      two groups that were examined. We found a circadian difference in the means of
      blood samples taken at 1-hour intervals, in respect of the cholesterol levels,
      the time difference being approximately two hours after the last ingestion. The
      cooperation with health insurance societies is a good possibility in view of the
      difficult situation of local or communal finances, to realise health education
      projects with financial support by health insurance societies. The statistical
      difference between the two examined populations for special risks shows that
      population groups with coronary insults in their anamnesis and hence treated "on
      target", yield statistically significantly better results in respect of
      cholesterol, systolic and diastolic blood pressure, than the group defined as a
      normal population.

PMID- 8580591
TI  - [Health reporting as a contribution to modernizing public health departments:
      evaluation of a public health project].
AB  - The aim of the project titled "Health Reporting and regional Health Policies" was
      to develop regional health reports. For this reason the project supported five
      local health departments (Bielefeld, Essen, Herne, Minden-Lubbecke and Munster)
      in North Rhine Westphalia and the state health department in Brandenburg in their
      attempt to implement reporting on a constant basis. Considering the lack of
      practical orientation and models, these responsibilities played an excess burden
      on the health departments, who were unable to cope. The main problems have been
      the complexity of the object "health/health system", the heterogeneity and
      insufficiency of existing data, and of course the poor resources of the
      departments in respect of know how, staff and equipment. For this reason, the
      model of development and strategy of implementation was pragmatic. The successful
      activities of regional health reporting in North Rhine Westphalia served as a
      basis, which was modified for the communal level. The following statement
      introduces the main elements of the concept and first results of the practical
      transformation.

PMID- 8580592
TI  - [Status of health policy and possible support to self-help groups].
AB  - Self-help groups strengthen an individual's sense of autonomy and self
      determination, and help to recover from diseases and other health-related
      problems. Participants mutually support each other within the group to promote a
      healthier approach to socio-psychological issues; they also conduct activities
      outside the group, especially counselling services for peers dealing with similar
      problems. In recent years, the number of groups throughout Germany rosen to
      approximately 60,000. The groups are mainly supported by self-help clearinghouses
      which have sprung up in many regions of western and eastern Germany over the last
      few years. This paper provides an overview of the development of self-help groups
      as well as the current state of support and funding in this area. Furthermore, it
      describes in detail the work performed by clearinghouses and the possibilities
      for cooperation with these new "liaison institutions".

PMID- 8580593
TI  - [Promoting self-help by a public health office--the example of the Unna
      district].
AB  - In the district of Unna support of self-help movement has been enjoying high
      priority for many years, giving a new orientation to the public health service
      towards a modern and more customer-friendly public service. Since January 1990 a
      self-help clearinghouse has been established by the section of health promotion
      supervised by the public health office. By now, three centres have been opened.
      The scheme of organisation, staffing and facilities, contents and working
      procedure, results and experiences are presented. It is quite obvious that
      support of the self-help movement should be one of the major tasks of public
      health service in the years to come.

PMID- 8580594
TI  - [The public health office and its partners: perspectives on cooperation between
      public health offices and self-help organizations].
AB  - Besides the three existing health sector entities in Germany: hospitals,
      established doctors and public health departments, a fourth area has developed,
      consisting of self-help organisations with their self-help groups. Today self
      help organisations have a very extensive knowledge about special diseases and
      handicaps. Combined with the psychological and social assistance which they
      afford, their knowledge helps the affected persons considerably. Nevertheless,
      this practical experience cannot replace the professionals' know-how. Within the
      local "Gemeinschaftsaufgabe Gesundheitsforderung" (common task of health
      promotion) the co-operation between laymen and professionals may be particularly
      supported by the Public Health Offices.

PMID- 8580595
TI  - [Cooperation in public health in the Bodensee district from the viewpoint of
      Vorarlberg].
AB  - Following a brief presentation of a few significant data and specifications in
      respect of the structure and organisation of the Austrian Public Health
      administration, general basic rules for across-the-border cooperation in the
      region of Lake Constance are outlined. The following subjects for such
      cooperation are listed: epidemiology and how to fight spring-summer
      meningoencephalitis, rabies, echinococcosis, AIDS/HIV. Other areas of cooperation
      are, for example. Health protection within the framework of prostitution, drugs
      and drug substitution, states of emergency (natural or other catastrophes),
      incidents or cases or topics concerning pharmaceuticals, pharmacology or
      pharmacies in general, and especially environmental protection and protection of
      natural resources in connection with the large drinking water reservoir Lake
      Constance. Future perspectives are roughly sketched in respect of possible closer
      cooperation and communication if occasion arises.

PMID- 8580596
TI  - [Sentinel public health offices--a new approach to determining public health
      relevant data by the public health service].
AB  - The discipline of environment-related health protection lacks continuously
      recorded data. Therefore, a three-year pilot project "Sentinel Public Health
      Offices" was initiated by the Ministry of Labour, Health and Social Welfare of
      Baden-Wurttemberg in 1992. Selected public health offices were instructed to
      conduct a series of three cross-sectional surveys of biological and effect
      monitoring among children attending the fourth grade of primary schools. The
      surveys were coordinated by the Provincial Public Health Office. During the pilot
      project the system of " Sentinel Public Health Offices" has proved successful not
      only in the continuous recording of data relevant to health. Its continuation as
      a permanent institution is contemplated.

PMID- 8580598
TI  - [Achieving uniformity of documentation in child and adolescent health care. Child
      and adolescent medicine electronic data processing scope convention as the basis
      of GBE, Dresden Public Health Service Congress, May 1995].
AB  - A uniform medical documentation system for school health care in the FRG does not
      seem to be realistic. On the contrary, a system based on singular modules could
      be adapted to the different local or regional requirements. This solution depends
      on two agreements, first of all the formal compatibility of the database, and
      secondly a compulsory basic panel to guarantee uniform youth health reporting.

PMID- 8580597
TI  - [Quality assurance in child and adolescent health care].
AB  - Quality assurance will be an important challenge not only in the private medical
      sector, but also in Public Health Services of Germany. In this contribution the
      basic principles of quality control are explained in a concise form: definition
      of quality, standard levels in quality assurance and control, evaluation and
      realisation. As far as possible some practical examples derived from the school
      and youth health services are explained. They can be modified to apply to other
      departments of Public Health Services.

PMID- 8580599
TI  - [Child development related health education--a responsibility of the public
      health service].
AB  - The Public Health Service is in a unique position with regard to the access to
      all socioeconomic groups including those who lack the alertness to make use of
      our health care system. This highlights it as a key factor in primary prevention.
      Interventions must focus on the individual situation of the addresses in order to
      motivate them to healthy behaviour. Health promotion for girls needs more
      attention, their knowledge and behaviour are decisive for the next generation.

PMID- 8580600
TI  - [Health promotion in Polish schools].
AB  - The health of the people is the basis of prosperity and development of the
      country. In 1986 the Ottawa Charta was resolved. Poland has already adopted the
      concept of the "health promoting# school in 1992. Promotion of health is a
      process whereby the population can achieve better control of their health status.
      The educational reform in Poland explored three avenues: health education,
      ecology, and social behaviour. The modern and manifold programmes of health
      promotion and ecology in schools are being realised, taking into consideration
      all the aspects of health care and protection of the environment, healthy style
      of living, responsibility for one's own health, knowledge of all disciplines of
      health. The author outlines the procedures and their course, describes the
      methods and assesses profits and results

PMID- 8580602
TI  - [Promoting breast feeding and the public health service].
AB  - This paper deals with the establishment of the National Breastfeeding Committee
      at the Robert-Koch-Institut and its activities. As the highest level scientific
      and advisory board for the German Federal Health Ministry the institute obtained
      permission from the state authorities to carry out a survey of the local health
      offices. A finding of this survey was that the different health offices
      apparently place different priorities on advising mothers in regard to
      breastfeeding. Some health offices offer medical counselling and others indicate
      that their counselling is carried out by non-medical personnel. In some cases the
      health offices reported a supply but no demand. We believe that the public health
      services should at least provide information on breastfeeding counselling in the
      community and on training opportunities for counsellors. The National
      Breastfeeding Commission will collect such information and provide it to the
      health offices and also give advice in the case of problems with regard to
      breastfeeding.

PMID- 8580601
TI  - [What physicians should currently observe in the area of dental health].
AB  - Several factors govern the development of human dental caries. The actual caries
      incidence in children depends greatly on fluoride consumption, reduction of
      fermentable sugar intake (in favour of the use of sugar substitutes), dental
      health habits and regular dental check-ups. A significant reduction of dental
      caries in children and young adults is achieved in many countries following these
      principles. However, there remains a group, about 25%, with a particularly high
      incidence of caries. Today, efforts are directed at detecting these risk
      subjects. Mutans streptococci and lactobacilli are the main causative bacteria of
      human dental caries. The initiation of dental caries is preceded by colonisation
      of the dentition by S. mutans, usually in early childhood. The early
      establishment of these bacteria in the mouth of human infants is dependent on
      intrafamilial--mainly maternal--transmission of saliva. The higher the level of
      S. mutans in the maternal saliva, the more likely is the colonisation of primary
      dentition by cariogenic bacteria. The earlier the colonisation, the higher the
      incidence of caries. Today we have new diagnostic aids: Simple microbiological
      tests to detect the individuals with high salivary levels of these cariogenic
      bacteria, so called SM-millionaires. The tests are also a good educational aid
      for motivating patients to individual prophylaxis. What could a paediatrician or
      gynaecologist do to help the dentist? He could inform the parents early enough to
      avoid saliva contacts. For example, the mother should not take the child's spoon
      or pacifier in her mouth. The dentist meets the children much later, at an age
      where they already have caries. The older methods, mentioned at the begin, are
      also still valuable.

PMID- 8580603
TI  - [Does income effect health? Analysis with data by the socioeconomic panel].
AB  - To determine the influence of income on health, the per capita weighted income is
      computed for every respondent of the German Socio-economic Panel. The effect of
      this income variable on health satisfaction and utilisation of medical services
      is examined via cross-sectional analysis, considering age and gender and taking
      the life circumstances under account (operationalized via professional activity
      level of qualification, partner and parenthood). Analysis of variance and
      regression show that health satisfaction grows with increasing income, while
      there is no evidence for similar effects of income on the utilisation of medical
      services.

PMID- 8580604
TI  - [Health economic aspects of dental medicine consultation and expert assessment by
      the health insurance medical service].
AB  - Within one year the Statutory Health Insurance Medical Service in Lower Saxony
      (Germany) gave expert opinion in 2,005 cases of treatment plans in dental
      medicine. The legal basis and structure of organisation are described as well as
      professional expertising criteria. Therapeutic schemes and estimations of
      treatment costs were used to ascertain the socioeconomic outcome of expert
      evaluation expressed the by exact equivalent in terms of money value. The single
      expert statement valued on average 2.230,-DM (approximately 1,500 US $) for an
      expertise recommending rejection of treatment cost coverage.

PMID- 8580605
TI  - [Academic recommendations on the need for treating carious deciduous molars and
      canine teeth in elementary school children--results of a survey of university
      dental clinics].
AB  - Supplying recommendations for dental treatment to primary school children with
      decayed deciduous molars and canines by the Public Health Service may cause
      conflicts. An inquiry by letter was performed to look for a consensus concerning
      the degree of necessity of the treatment of decayed deciduous teeth. The German
      dental clinics who answered the questions unanimously disapproved the "Retaining"
      of decayed deciduous molars and canines without treatment; most of them
      recommended a conservative therapy until shortly before they become
      physiologically defunct, or, alternatively, the removal of the decayed teeth.

PMID- 8580606
TI  - [Effects of 2 reimbursement models on house calls by general practitioners].
AB  - This study compares the effects of the salary payment in the former GDR with the
      fee for service remuneration in Germany for outpatient service. The investigation
      focused on home visits 3 by family doctors in Magdeburg in the first two quarters
      of the years 1985 and 1992. The retrospective study based on existing
      documentations. Main questions were the modification of frequency resp. nature
      and matter of home visits. The frequency of home visits increased by about 134%.
      Distributed by age-groups, the home visits at patients up to the age of 55 showed
      only a small increase. However, the increase with patients between 60 and 79
      years of age was 350%. In particular, diseases of the ICD Group VII (diseases of
      the vascular system) were affected by the increase. In contrast to this home
      visits of nurses were influenced to a lesser degree by the system changes. These
      are indications that the increase in the home visits is not due to an increased
      demand for them.

PMID- 8580607
TI  - [Arthroses of the finger joints and thumb saddle joint and occupationally related
      factors].
AB  - In a one-to-one matched case control study, 37 cases with rhizarthrosis (31
      female, 6 male) and 44 cases with osteoarthritis in the finger joints (35 female,
      9 male) were compared to their matches equal in sex and age regarding
      occupational strains. For calculating the odds ratios matching was maintained. In
      females the risk of rhizarthrosis was elevated for typists (OR 5.0, CI 1.27
      19.59) and for work involving dexterity (OR 2.0, CI 0.77-5.23). In both sexes an
      elevated odds ratio for osteoarthritis in the finger joints was found for
      repetitive work (OR 3.8, CI 1.52-9.49).

PMID- 8580608
TI  - [Statistical description of health complaints after pyrethroid exposure--a
      comparison of exposed groups].
AB  - In respect of 128 pyrethroid-exposed persons, data on subjective health
      impairment were collected by applying a self-administered questionnaire.
      Participants--83 female and 45 male--determined their health status using a scale
      for the strength of their complaints. Health complaints were measured by 70
      variables and were divided into 6 symptom groups. A low exposure and a high
      exposure group was defined by the number of pyrethroid applications (once versus
      several). We computed mean values for all 70 variables stratified according to
      gender and exposure group. Comparison shows that for nearly all variables highly
      exposed women reported stronger health complaints than low exposed women. This
      uniform trend is not seen in men. For a condensed presentation of differing
      health complaints between exposure groups, we defined standardised scores for
      each of the 6 symptom classes. Women with elevated exposure show increased scores
      for all 6 symptom groups, one difference being significant (p = 0.018) and two
      differences being of borderline significance (p = 0.061 and p = 0.073). For
      highly exposed men only two scores are elevated and none is significant. However,
      it is pointed out that the high-exposure group comprises only 9 men.

PMID- 8580609
TI  - [Reappearance of tuberculosis, risks and consequences!].
AB  - WHO estimates that worldwide cases of TB will amount to 8.8 million in 1995 and
      11.9 million in 2005. Compared with the estimated amount of TB cases of 7.5
      million in 1990 there is a rise by 16.3 percent for 1995 and by 57.6 per cent for
      2005. Treatment costs for TB are relatively low. If properly administered the
      treatment is effective in more than 95 percent of all cases. The mortality for TB
      estimated worldwide in 1992 and related to a population of 100,000 confirms that
      South East Asia and Subsaharian Africa show the highest mortality. The existing
      statistical data for Germany give an indication that the morbidity rate of newly
      acquired TB cases has increased only slightly. This increase is exclusively due
      to immigrants. The emergence of TB in Germany is not so serious that preventive
      measures on a large scale and at high cost are required. Doctors should be made
      aware of the problems of TB and should include this disease in their differential
      diagnosis. As is to be expected, the rate of new cases of TB is higher for
      members of disadvantaged groups and recipients of social welfare. The potential
      risk is growing wherever there may be unfavourable economic development. More
      attention will have to be given to those groups of people who carry a higher risk
      of infecting others. Between 5 and 10 per cent of HIV-infected patients in
      Germany also contract TB. WHO estimates that there will be about 88.2 million
      cases of TB worldwide during the ten years period from 1990 to 1999. About 8
      million of these cases could be attributable to HIV infection.

PMID- 8580610
TI  - [Recommendations for changing microbiological examination parameters in filling
      bottled water to comply with the mineral and drinking water regulation].
AB  - Microbiological Pollutions in Mineral, Spring and Table Waters have different
      potency according to health hazards or to noncompliance with good manufacturing
      practices. Therefore, the microbiological parameters of mineral water and table
      water directives should be reexamined for their suitability. Only Escherichia
      coli is an indicator of faecal pollution and therefore an indicator of health
      hazards. Enterobacteriaceae (coliform and noncoliform), Pseudomonas aeruginosa
      and elevated colony counts mainly suggest noncompliance with good manufacturing
      practices. Sulphite-reducing clostridia and faecal streptococci are worthless
      indicators at the moment because of inadequate analytical methods. In addition,
      investigations on Staphylococcus aureus are recommended at least for bottled
      waters which are declared to be suitable for the preparation of infant food. From
      this point of view, different procedures for penalty and marketing are also
      discussed.

PMID- 8580611
TI  - [Survival ability of Trichomonas vaginalis in mineral baths].
AB  - The role of mineral thermal baths and particularly of bath fittings such as
      benches and toilet seats in the spreading of Trichomonas vaginalis is
      controversial. In order to clarify the possibility of transmission by smear
      infection of this ubiquitous urogenital parasite the ability to survive was
      investigated in 11 mineral baths in Baden-Wurttemberg by contamination of water
      samples of varying mineral content. In addition, Trichomonas-contaminated water
      samples were placed in Petri-dishes on different benches in the bath area to
      determine the different milieu-factors influencing survival and thus the
      possibility of smear infections. The determination of viable cells was carried
      out by recultivation and semiquantitative extinction measurement. The survival
      time of Trichomonas vaginalis in the water samples of the 11 mineral baths varied
      considerably from 30 min up to more than 3 hours. The total mineral content
      played the most important role. When exposed in Petri dishes in addition the
      evaporation of the medium (mineral water) is of importance. Generally at high
      evaporation rates the cells will lose viability faster than in closed tubes. But
      also in open dishes in 4 mineral baths viable Trichomonads were still detectable
      after 3 hours. Generally the ability of Trichomonas vaginalis to survive in water
      of a total mineral content of 0.05-2.2% is increased to such an extent that
      infection is theoretically possible. Transmission in the mineral pool itself
      appears nevertheless highly unlikely due to the dilution effect of the enormous
      water volume. However transmission of infection via wet, contaminated benches and
      toilet seats cannot be generally ruled out.

PMID- 8580612
TI  - [Comparison of 2 federal regulation proposals for public health service].
AB  - The provincial governments of the German Laender Niedersachsen (Lower Saxony) and
      Sachsen-Anhalt (Saxony-Anhalt) both present a modern Act for Public Health
      Service to replace the 1934 standardisation act. Most important in my opinion is
      that local Public Health offices are competent to coordinate. The Sachsen-Anhalt
      bill requires them to hold regional health conferences, to integrate self-help
      groups in the health sphere or to locate gaps where health care is insufficient.
      The catalogue of Sachsen-Anhalt concerning Health Aids and Public Health Services
      is also wider than in Niedersachsen. Both Laender are proceeding in the right
      direction towards a modern health administration.

PMID- 8580613
TI  - The detection and management of dyslipidaemia in children and adolescents.
AB  - Previous algorithms regarding treatment of children with dyslipidaemia do not
      distinguish sufficiently between children at very high risk for cardiovascular
      disease and those with less exceptional risk. We propose that physicians assess
      risk, taking into consideration the nature of the genetic disorder, the severity
      of hypercholesterolaemia and the family history. Screening should be limited to
      children with suspected familial hypercholesterolaemia. Guidelines for
      individualized dietary and drug therapy are suggested.

PMID- 8580614
TI  - Development of human peripheral hearing revealed by brainstem auditory evoked
      potentials.
AB  - Development of human peripheral hearing from birth to 6 years was investigated by
      recording brainstem auditory evoked potentials (BAEPs). The threshold of BAEPs
      decreased rapidly during the first 3 months after birth (2.7 dB/week during the
      neonatal period, 2.6 dB/month at 1-3 months), after which further decrease
      occurred more slowly but continued through 1 year of age (0.26 dB/month at 3-12
      months). A few days after birth, the threshold was 18 dB higher compared to the
      adults, and progressively decreased to 10, 5 and 2 dB at 1, 3 and 12 months,
      respectively. The latencies of waves I and V decreased as a function of age at a
      rate of 0.01 and 0.05 ms/week during the neonatal period, 0.02 and 0.10 ms/month
      at 1-3 months and 0.014 and 0.076 ms/month at 3-12 months, respectively. Adult
      latency value was attained by 2 and 4 years for waves I and V, respectively.
      These findings suggest that although the ear is reported to be almost adult-like
      at birth, the immaturity in neural functional properties limits auditory
      sensitivity during early childhood. It appears that human peripheral hearing
      threshold decreases rapidly through the third postnatal month and thereafter
      continues to improve slowly through early childhood. It is postulated that the
      first 3 months after birth are likely to be a critical period in postnatal
      development of human peripheral hearing.

PMID- 8580615
TI  - The impact of lactation centres on breastfeeding patterns, morbidity and growth:
      a birth cohort study.
AB  - The influence of lactation centres on breastfeeding patterns, morbidity and
      nutritional status was assessed through a longitudinal study from birth up to the
      age of 6 months among 605 mothers and newborns in Guaruja, Sao Paulo, Brazil.
      Children recruited in the perinatal period who subsequently attended the
      lactation centres (54%) were exclusively breastfed significantly more at 4 months
      (43 versus 18%) and at 6 months of age (15 versus 6%), than non-attenders, even
      after adjusting for confounders. Also, attenders presented less diarrhoea in the
      last fortnight than non-attenders (10 versus 17%), and their weight for age was
      significantly better (mean z-scores of 0.26 and 0.02, respectively). Lactation
      centres are effective in promoting breastfeeding, and their use in areas with
      short breastfeeding duration should be considered. This is the first report of a
      significant impact of a breastfeeding promotion programme on children's morbidity
      and growth.

PMID- 8580616
TI  - Body growth in children with polycystic kidney disease. Arbeitsgemeinschaft fur
      Padiatrische Nephrologie.
AB  - We analysed the body growth of 121 prepubertal children with polycystic kidney
      disease participating in a longitudinal multicentre study. The patients were
      followed from an age of 1 to 9 years in girls and 1 to 10 years in boys over a
      mean period of 3.6 years. Children with end-stage renal disease were excluded.
      Fifty-four patients had the autosomal dominant form of the disease and 67 the
      autosomal recessive form. At last observation, 2% of patients with the dominant
      form and 28% of those with the recessive form had an estimated glomerular
      filtration rate of < 60 ml/(min 1.73 m2). At first observation, the mean height
      SD score (SDS) in patients with the dominant form was almost the same as in
      controls, whilst in those with the recessive form it was significantly decreased
      (girls -0.82 SDS, boys -0.68 SDS, p < 0.001). During the follow-up the height SDS
      decreased slightly in both groups (NS). In patients with autosomal recessive
      kidney disease the degree of growth retardation appeared to be related to renal
      function: at last observation the height of girls with an estimated glomerular
      filtration rate of < 60 ml/(min 1.73 m2) was more retarded than that of boys
      (mean -2.1 SDS versus -1.5 SDS, NS). The height SDS and renal function at last
      observation correlated in girls (r = 0.83, p < 0.001) but not in boys (r = 0.55)
      with the recessive form. No correlation was found between the height SDS and
      hypertension. The weight-for-height SDS at onset was significantly reduced in
      patients with the recessive form with decreased renal function. Our data suggest
      that the autosomal recessive, but not the dominant, form of polycystic kidney
      disease is associated with early growth retardation, which seems to be more
      severe in girls, probably due to the more rapid deterioration of renal function.

PMID- 8580617
TI  - Follow-up of antibodies to growth hormone in 210 growth hormone-deficient
      children treated with different commercial preparations.
AB  - The aim of the study was to evaluate the immunogenicity of different commercial
      recombinant-growth hormone preparations. The presence of antibodies to growth
      hormone was tested in 210 growth hormone-deficient children at 6-month intervals
      during treatment for 6-66 months. The patients were treated with three
      preparations (groups A, B and C of 70 cases each) having the authentic growth
      hormone sequence. Groups A and B received hormone synthesized by the recombinant
      DNA technique in E. coli, while the group C preparation was produced in a
      mammalian cell line. The preparations showed poor immunogenicity and antibodies
      were found as follows: 1.4% in patients of group A (1 case: binding capacity 0.2
      mg/l and Ka 3.5 10(7) l M-1), 2.8% in patients of group B (2 cases; case 1
      binding capacity 0.7 mg/l and Ka 1.5 10(7) l M-1; case 2 binding capacity 0.04
      mg/l and Ka of 1.8 10(8) and 6.5 10(6) l M-1), and 8.5% in group C (6 cases;
      binding capacity from 0.4 to less than 0.02 mg/l, Ka from 1.6 10(7) to 3.8 10(8)
      l M-1). Only two patients of group C presented the antibodies in two subsequent
      examinations; in the other patients the positivity was found once. In all
      patients positive samples were found at intervals of 6-24 months after the start
      of therapy. In all antibody-positive patients growth velocity presented no
      decrease at the time of antibody detection and was never different to that of
      negative patients. We conclude that the three commercial preparations examined
      showed poor immunogenicity without clinical relevance.

PMID- 8580618
TI  - High-dose methotrexate causes short-term suppression of growth in rabbits.
AB  - Bone growth in rabbits was measured using roentgen stereophotogrammetric analysis
      (RSA), a method for accurate measurement of the distance between metallic markers
      inserted into long bones. Injections of methotrexate (Mtx) were given to five
      rabbits and tibial growth was measured daily for 5 days. Im injections of Mtx 100
      mg/kg body weight, followed by folinic acid "rescue" 48 h later, had no influence
      on growth. Intraperitoneal injection of Mtx 1000 mg/kg body weight resulted in a
      clear reduction in daily growth during the study period. The rabbits were given
      folinic acid "rescue" 24, 36 and 48 h after Mtx injection and showed no symptoms
      or signs of Mtx toxicity. Serum levels of Mtx, 3 days after the high-dose
      injection, declined successively but were still measurable after 72 h. Using RSA,
      the short-term influence of cytostatic drugs can be evaluated in an experimental
      setting. The effect of Mtx on growth in rabbits was discernible only at very high
      doses. Suppression of growth was moderate, appeared soon after injection of Mtx
      and was of moderate duration.

PMID- 8580619
TI  - Fruit juice malabsorption: not only fructose.
AB  - Malabsorption of free fructose, when ingested in excess over glucose, is
      considered a significant factor in apple juice induced diarrhoea. Absorption of
      the carbohydrates in fruit juices was investigated by means of the hydrogen
      breath test in 15 healthy children aged 2.2-6.4 years, consuming 15 ml kg-1 of
      each juice with a maximum of 375 ml. Incomplete absorption was found following
      the ingestion of apple juice (5/5), grape juice (10/10) and bilberry juice
      (8/10), although the last two contain equivalent concentrations of fructose and
      glucose. When the same tests were repeated after yeast treatment of the juices,
      which leads to major reductions in fructose and glucose contents, malabsorption
      was found to persist. No symptoms were observed following any of the tests. Our
      results suggest a significant role for other carbohydrates than fructose,
      possibly those originating from the fruit skin, with respect to fruit juice
      induced breath hydrogen excretion.

PMID- 8580620
TI  - Electrophysiological assessment of brain function in severe malnutrition.
AB  - Brain function in 10 severely malnourished children and matched controls was
      assessed using spectral analysis of electroencephalographic responses to photic
      driving during slow-wave sleep. The percentage power in the classical EEG broad
      band domains was derived from temporo-occipital records. The malnourished group
      (5-23 months old; z-score height-for-age -3.2 +/- 0.3, weight-for-height -2.5 +/-
      0.3) were tested on admission and on discharge from hospital. No significant
      differences were found between admission and discharge. Significant differences
      were found between malnourished and control groups, in the alpha 1 band in the
      undriven EEG, and in the alpha/beta 1 power ratio while driving at 8 Hz. These
      electrophysiological abnormalities, persisting despite somatic rehabilitation,
      must be associated with the chronic rather than the acute aspects of
      malnutrition, and can index the deviation of brain function from normality.

PMID- 8580621
TI  - Latent coeliac disease in Italy. The SIGEP Working Group on Latent Coeliac
      Disease. Italian Society for Paediatric Gastroenterology and Hepatology.
AB  - The term latent coeliac disease applies to patients who have a normal jejunal
      biopsy while taking a normal diet and, at some other time, before or since, have
      had a flat jejunal biopsy recovering on a gluten-free diet. Nineteen such
      patients were identified after a multicentre search conducted under the auspices
      of the Italian Society for Paediatric Gastroenterology and Hepatology (SIGEP).
      Serological data and histological material suitable for morphometric analysis
      were available from 10 and 8 patients, respectively, while they were on a gluten
      containing diet. Neither gliadin antibodies nor increased density of
      intraepithelial lymphocytes are obligate markers of latent coeliac disease;
      endomysial antibodies are likely to be best predictors of evolution towards
      villous atrophy. Prospective studies are needed to allow a more precise
      definition of latent coeliac patient features.

PMID- 8580622
TI  - IgA bovine serum albumin antibodies are increased in newly diagnosed patients
      with insulin-dependent diabetes mellitus, but the increase is not an independent
      risk factor for diabetes.
AB  - We studied the significance of antibodies to bovine serum albumin (BSA) as a risk
      factor for insulin-dependent diabetes mellitus (IDDM) in a case-control setting.
      IgA and IgG antibodies to BSA and ovalbumin were measured from sera of 104
      patients with newly diagnosed IDDM and of 111 matched controls by enzyme-linked
      immunosorbent assay. Patients with diabetes had significantly higher levels of
      IgA antibodies to BSA (p = 0.003); IgG antibodies also tended to be higher (p =
      0.08). Levels of IgA antibodies to ovalbumin were similar in the patients and
      controls, but IgG antibodies were higher in controls (p = 0.02). When antibodies
      to BSA, beta-lactoglobulin, whole cow's milk and islet cell antibodies were
      studied as risk determinants of IDDM in a multivariate, logistic regression
      analysis, IgA antibodies to beta-lactoglobulin and to cow's milk were
      independently associated with the risk (p = 0.037 and 0.048, respectively), while
      antibodies to BSA were not a significant risk factor. The results question the
      role of BSA as a cross-reacting antigen with pancreatic beta-cell surface
      proteins in the aetiology of IDDM.

PMID- 8580623
TI  - Carriage of Haemophilus influenzae and Streptococcus pneumoniae in healthy
      Chinese and Vietnamese children in Hong Kong.
AB  - Nasopharyngeal carriage of Haemophilus influenzae and Streptococcus pneumoniae
      was studied in 621 healthy Chinese children and 300 healthy Vietnamese children
      aged from 2 months to 5 years in Hong Kong. The carriage rate of H. influenzae
      type b in Vietnamese children was 1.3% (CI 0.04-2.63); it was zero in Chinese.
      The carriage rate of non-typable H. influenzae was 5.8% (CI 1.4-7.6%) in Chinese
      and 65.4% (CI 58.9-69.8%) in Vietnamese. The carriage rates of S. pneumoniae were
      10.8% (CI 8.3-13.2%) and 55.7% (CI 50.1-61.3%) in Chinese and Vietnamese
      children, respectively. Univariate and multivariate logistic regression analyses
      were performed to search for factors associated with differences in carriage
      rates of both H. influenzae and S. pneumoniae between Chinese and Vetnamese
      children. Although older age, smaller living area and parental smoking were
      associated with higher carriage rates, these could not explain the remarkably low
      carriage rates of both bacteria in Chinese children.

PMID- 8580624
TI  - Gamma delta T lymphocytes in mumps meningitis patients.
AB  - Flowcytometric analysis on T-cell subpopulations in the blood and cerebrospinal
      fluid (CSF) of 10 children with mumps meningitis (MM) revealed that the
      proportion of lymphocytes which bore the gamma delta T-cell receptor for antigen
      was significantly higher in CSF than in autologous and heterologous blood
      samples. gamma delta T-cell values in CSF of MM patients were also significantly
      higher than those calculated in CSF specimens from nine children with non
      inflammatory neurological disorders. Whether and how the expanded CSF gamma delta
      T-lymphocyte subset, either CD8+ or double-negative (CD4-/CD8-), contributes to
      the eradication of mumps virus infection from the central nervous system
      represents a central focus of our ongoing research.

PMID- 8580625
TI  - Chronic active Epstein-Barr virus infection in children in Japan.
AB  - The patients with chronic active Epstein-Barr virus infection (CAEBV) in
      childhood in Japan are described. Among 39 registered cases, 20 patients were
      males and 19 were females. Unlike the X-linked lymphoproliferative syndrome,
      there was no hereditary background. The incidence of hypersensitivity to mosquito
      bites was high (31.3%) as a past history. Most patients exhibited hepatomegaly
      (92.3%), splenomegaly (87.2%) and fever (84.6%). The incidence of absent anti-EB
      virus nuclear antigen titres was unexpectedly low (17.1%). Lymphoreticular
      disorders and cardiovascular diseases were major complications. Twenty-four
      (61.5%) patients died 6 months to 8 years after the onset, mainly of hepatic
      failure (eight cases), cardiac failure (five cases), virus-associated
      haemophagocytic syndrome (three cases) and haematological malignancies (two
      cases). This study reveals the CAEBV in Japan has several clinical features and
      should be informative for the pathogenesis of EB virus.

PMID- 8580626
TI  - The role of fever on cerebrospinal fluid glucose concentration of children with
      and without convulsions.
AB  - In febrile convulsions glucose concentrations are known to increase both in the
      blood and cerebrospinal fluid (CSF). The reason behind this increase is, however,
      incompletely understood. We have studied the effects of convulsion and fever on
      the CSF and blood glucose concentrations in four different groups of children:
      febrile and non-febrile children, with and without convulsions. The concentration
      of glucose in the CSF was significantly higher in febrile children with (4.4 +/-
      0.1 mmol/l, mean +/- SEM n = 35, p < 0.01. ANOVA, Duncan's test) and without
      convulsions (3.9 +/- 0.2 mmol/l, n = 22, p < 0.05) than in non-febrile, non
      convulsive children (3.3 +/- 0.1 mmol/l, n = 21). In non-febrile convulsive
      children, the CSF glucose concentration was 3.7 +/- 0.2 mmol/l (n = 10). Both
      fever and seizures increased the CSF glucose levels (p < 0.0001) and p = 0.028,
      respectively, analysis of covariance). There was a linear correlation between the
      body temperature and concentration of glucose in the CSF (r = 0.454, p < 0.0001,
      n = 88, Pearson's correlation analysis). The changes in blood glucose
      concentrations between the groups paralleled those found in the CSF. Our results
      show that hyperglycaemia and an increase in the CSF glucose concentration in
      febrile convulsions is not explained just by a stress reaction, evoked by the
      seizure, as has been hypothesized earlier, but by the influence of increased body
      temperature as well.

PMID- 8580627
TI  - An assessment of sources of information in post-perinatal infant death reviews.
AB  - The objective of this study was to identify adverse social and medical factors
      contributory to post-perinatal deaths and at which stage of the case study each
      factor was found. The sources of information assessed were: (i) recorded data
      from case notes, laboratory and postmortem findings, and (ii) created information
      from (a) home interview and (b) case discussion held in the family doctor's
      office. The deaths were categorized into seven clinicopathological groups and
      adverse factors into general demographic and personal psychosocial. Among the 87
      sequential post-perinatal infant deaths, 325 adverse factors were identified; of
      these, 125 (38%) were judged to be actionable by the carers. Of 183 (56%) adverse
      factors found in the case notes, only 36 were actionable. Forty-five more adverse
      factors were found at home interview; 26 (58%) of these were actionable. At case
      discussion another 97 adverse factors were revealed; 63 (65%) were actionable,
      thus proving the most important source of actionable information.

PMID- 8580628
TI  - Influence of body temperature on thyrotropic hormone release and lipolysis in the
      newborn infant.
AB  - The present study investigated possible interactions between body temperature,
      lipolysis and thyrotropin (TSH), the only hormone with a documented lipolytic
      effect in vitro in newborn infants. Healthy infants were either nursed in the
      usual way (n = 18) or protected from a decrease in body temperature (n = 17)
      during the first postnatal hour. The infants' axillary temperatures were measured
      immediately after birth and after 10 and 60 min. Blood samples were collected
      from the umbilical vein and from the infants 10 and 60 min after birth for
      analysis of TSH, glycerol, free fatty acids, 3-OH-butyric acid and glucose. We
      found that the mean (+/- SD) infant axillary temperature was 37.6 +/- 0.4 degrees
      C immediately after birth. In the routinely nursed infants, body temperature
      decreased to 37.0 +/- 0.5 degrees C at 10 min (p = 0.01) and to 36.6 +/- 0.4
      degrees C at 60 min (p = 0.01); the cold-protected infants maintained their fetal
      temperature at 60 min of age. There was a four-fold increase in plasma TSH levels
      at 10 min, independent of the infant's body temperature, and the hormone level
      remained invariably high at 60 min. Plasma glycerol levels increased
      progressively at 10 min (p = 0.01) and 60 min (p = 0.01) in both infant groups,
      but were higher (p = 0.02) in the routinely nursed infants at 60 min. No
      significant relationship was found between TSH and glycerol levels. Infant body
      temperature did not affect the levels of free fatty acids, 3-OH-butyric acid or
      glucose. We conclude that the change in environmental temperature as a result of
      extrauterine adaptation causes thermal stimulation of the infant's body surface
      which leads to activation of the hypothalamic-pituitary TSH axis, resulting in
      maximal TSH release, and thus to induction of the lipolytic process. A decrease
      in body temperature may be an additive stimulus for further enhancement of
      lipolysis.

PMID- 8580629
TI  - Early [18F]FDG positron emission tomography in infants with hypoxic-ischaemic
      encephalopathy shows hypermetabolism during the postasphyctic period.
AB  - Six full-term infants suffering from perinatal asphyxia and with moderate or
      severe hypoxic-ischaemic encephalopathy were investigated by positron emission
      tomography (PET). Regional cerebral metabolic rates of glucose (rCMRgl) were
      determined using [2-18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET scans at a
      median age of 2.5 days (range 2-5 days). Localized increases in rCMRgl were
      visually observed in five infants. In a subgroup of three infants, absolute
      values of rCMRgl in different brain regions were calculated. In all cases the
      results of the PET studies were in good agreement with those of the
      neuroradiological, neurophysiological and clinical investigations. Information
      indicating pathophysiological events could be extracted earlier with PET than
      with conventional morphological imaging techniques. We conclude that [18F]FDG-PET
      scans performed in critically ill, asphyxiated infants very soon after birth
      provide valuable information for the prediction about neurological outcome.

PMID- 8580630
TI  - Early protein oxidation in the neonatal lung is related to development of chronic
      lung disease.
AB  - Free radical-mediated oxidation of proteins may impair their function and cause
      cellular damage. We studied pulmonary protein oxidation and its association with
      the development of chronic lung disease in 61 newborn infants (mean gestational
      age 31.1 +/- 4.0, range 24-41 weeks) requiring intensive care with oxygen
      therapy. Protein oxidation was quantified as protein carbonylation in tracheal
      aspirates recovered daily during the first week of life. Mean carbonyl
      concentration was 3.5 +/- 1.6 mumol/mg protein. Negative correlations existed
      between protein carbonylation during days 2-4 and gestational age (day 2: r = 
      0.37, p = 0.01; day 3: r = -0.48, p = 0.001; and day 4: r = -0.33, p = 0.03).
      Patients who developed bronchopulmonary dysplasia showed significantly higher
      protein carbonylation on days 1-6 (all p < 0.05). In multiple regression analysis
      explaining bronchopulmonary dysplasia, using gestational age, inspired oxygen on
      days 1-3 and protein carbonylation on day 3 as independent variables, only
      protein carbonylation remained significant. We conclude that immaturity is the
      most important factor explaining free radical-mediated pulmonary protein
      oxidation in newborn infants and that oxidation of proteins is related to the
      development of chronic lung disease.

PMID- 8580631
TI  - Circulatory effects of ventilator rate and end-expiratory pressure in unparalysed
      preterm infants.
AB  - Impairment of cerebrovascular autoregulation may be important in the pathogenesis
      of ischaemic brain injury in preterm infants. A previous study in ventilated
      preterm infants paralysed with pancuronium showed that changes in cerebral blood
      flow velocity (CBFV) were related to concomitant changes in arterial blood
      pressure. In a similar study in unparalysed infants, changes in CBFV in response
      to changes in ventilator rate or end-expiratory pressure were independent of
      associated changes in the arterial blood pressure. These results emphasize the
      importance of avoiding large swings in blood pressure in paralysed infants.
      Whether alternative paralysing agents have similar effects warrants further
      study.

PMID- 8580632
TI  - Variable oxygenation response to inhaled nitric oxide in severe persistent
      pulmonary hypertension of the newborn.
AB  - The causes of variable responsiveness to inhaled nitric oxide (NO) in Persistent
      Pulmonary Hypertension of the Newborn (PPHN) are unknown. The changes in the
      severity of respiratory failure after the onset of inhaled NO (maximal dose 20
      ppm) were studied in 13 consecutive neonates with severe PPHN. Response was
      defined as a sustained decrease of alveolar-arterial oxygen gradient (AaDO2) by >
      20%, or a decrease in oxygenation index (OI) by > 40%. Six neonates had a rapid
      response within 30 min, three had an intermediate response within 8 h, and three
      had a delayed response within 12 h after the onset of NO. Three infants with
      birth asphyxia responded rapidly to inhaled NO. One infant with sepsis did not
      respond, and two with suspected sepsis had a delayed response. The infants with
      Meconium Aspiration Syndrome and idiopathic PPHN had a variable response time.
      Twelve neonates required 4 to 14 days of mechanical ventilation and survived.
      Infants with PPHN may benefit from a trial of inhaled NO therapy that exceeds 30
      min. The variability of the response time to inhaled NO is likely to be
      multifactorial and dependent on the disease process associated with PPHN.

PMID- 8580633
TI  - Pneumocystis carinii pneumonia in preterm infants: report of two cases
      successfully diagnosed by non-bronchoscopic bronchoalveolar lavage.
AB  - We present two cases of Pneumocystis carinii pneumonia in apparently
      immunocompetent preterm infants presenting with unexplained respiratory distress
      associated with a predominantly interstitial process on the chest radiograph.
      Definite diagnosis was promptly established on the detection of cyst forms in the
      lung fluid obtained by non-bronchoscopic bronchoalveolar lavage, and a favourable
      outcome was achieved.

PMID- 8580634
TI  - Sodium supplementation optimizes weight gain in preterm infants.

PMID- 8580635
TI  - Severe Rh(D) immunization: anti-D quantitation and treatment possibilities during
      pregnancy and after birth.
AB  - An extremely aggressive Rh(D), (C) and Kell alloimmunization during pregnancy is
      reported. Exceptionally high concentrations of anti-D were observed in the
      mother, in the fetus and in the amniotic fluid, indicating an active transport
      across the placenta and a passive excretion into the amniotic fluid. Treatment
      during pregnancy included maternal plasmapheresis and high-dose intravenous
      immunoglobulin. Intravascular transfusions were given to the fetus. Postpartum
      the newborn was given immunoglobulin, one exchange transfusion and four top-up
      transfusions. In the newborn the elimination rate of anti-D could be followed.
      Not until almost 4 months postpartum did the anti-D concentration drop below the
      level of detection. This coincided with an elevated reticulocyte production and
      appearance of the child's true blood group in parallel with ceasing need for
      blood transfusions. Elimination rate and absolute anti-D values can be used as a
      prognostic tool to predict the need of blood transfusions. Immunoglobulin
      treatment can also be considered as an optional form of treatment in newborns
      affected by alloimmunization.

PMID- 8580636
TI  - Methaemoglobinaemia with high-dose nitric oxide administration.

PMID- 8580637
TI  - A prospective study of cow's milk allergy in Turkish infants.

PMID- 8580638
TI  - Imperforate anus, bilateral hydronephrosis, bilateral undescended testes and
      pituitary hypoplasia: a variant of Hall-Pallister syndrome or a new syndrome.
AB  - A patient with multiple congenital malformations, including imperforate anus,
      bilateral cryptorchidism and microphallus, is described. At 4 months of age the
      infant had generalized convulsions and hypoglycaemia. Bilateral hydronephrosis
      was diagnosed at 8 months of age. At 10 months he was diagnosed as having
      panhypopituitarism secondary to anterior pituitary hypoplasia, shown on CT and
      MRI scans. This clinical picture partially resembles that of Hall-Pallister
      syndrome. However, the absence of some typical features such as craniofacial and
      limb abnormalities and, above all, hypothalamic hamartoblastoma, would also
      suggest the possibility of a new, previously unreported, syndrome.

PMID- 8580639
TI  - Congenital erythropoietic porphyria associated with nephrotic syndrome and renal
      siderosis.
AB  - A 9-year-old boy with typical features of congenital erythropoietic porphyria who
      had received more than 50 blood transfusions developed the steroid-resistant
      nephrotic syndrome in the presence of normal glomerular function and glucosuria.
      Renal biopsy showed focal segmental glomerulosclerosis and widespread iron
      deposits. Magnetic resonance scanning revealed advanced siderosis of liver and
      kidneys. During a 4 year treatment by desferrioxamine the serum ferritin level
      was reduced, proteinuria dropped and serum proteins increased whilst glomerular
      filtration decreased slowly. It is suggested that the nephrotic syndrome may be a
      consequence of renal siderosis amenable to iron-chelating therapy.

PMID- 8580640
TI  - Clinical and immunohistochemical findings in a case of neonatal Marfan syndrome.
AB  - A newborn girl with extreme cardiomegaly discovered by fetal ultrasound after 34
      gestational weeks is presented. The girl was delivered through a Caesarean
      section. After birth, multiple skeletal stigmata and generalized cardiac
      involvement with abnormal valves and dilated great arteries suggested Marfan
      syndrome. The girl died at the age of 10 h. The postmortem examinations showed
      cardiovascular lesions typical of Marfan syndrome. Immunofluorescence studies
      from cultured fibroblasts of the patient showed decreased amounts of
      immunostained fibrous material, supporting the clinical diagnosis of a severe
      Marfan syndrome.

PMID- 8580641
TI  - Tongue necrosis due to vasculitis.
AB  - We describe a 7-year-old boy with necrosis of the tongue due to a generalized
      vasculitis, with symptoms and signs consistent with periarteritis nodosa and
      appearing after an infection with streptococci. Approximately one-third of the
      tongue had to be extirpated.

PMID- 8580642
TI  - Effects of organic compounds on the degradation of p-nitrophenol in lake and
      industrial wastewater by inoculated bacteria.
AB  - Many microorganisms fail to degrade pollutants when introduced in different
      natural environments. This is a problem in selecting inocula for bioremediation
      of polluted sites. Thus, a study was conducted to determine the success of four
      inoculants to degrade p-nitrophenol (PNP) in lake and industrial wastewater and
      the effects of organic compounds on the degradation of high and low
      concentrations of PNP in these environments. Corynebacterium strain Z4 when
      inoculated into the lake and wastewater samples containing 20 micrograms/ml of
      PNP degraded 90% of PNP in one day. Addition of 100 micrograms/ml of glucose as a
      second substrate did not enhance the degradation of PNP and the bacterium
      utilized the two substrates simultaneously. Glucose used at the same
      concentration (100 micrograms/ml), inhibited degradation of 20 micrograms of PNP
      in wastewater by Pseudomonas strain MS. However, glucose increased the extent of
      degradation of PNP by Pseudomonas strain GR. Phenol also enhanced the degradation
      of PNP in wastewater by Pseudomonas strain GR, but had no effect on the
      degradation of PNP by Corynebacterium strain Z4. Addition of 100 micrograms/ml of
      glucose as a second substrate into the lake water samples containing low
      concentration of PNP (26 ng/ml) enhanced the degradation of PNP and the growth of
      Corynebacterium strain Z4. In the presence of glucose, it grew from 2 x 10(4) to
      4 x 10(4) cells/ml in 3 days and degraded 70% of PNP as compared to samples
      without glucose in which the bacterium declined in cell number from 2 x 10(4) to
      8 x 10(3) cells/ml and degraded only 30% PNP. The results suggest that in
      inoculation to enhance biodegradation, depending on the inoculant, second organic
      substrate many play an important role in controlling the rate and extent of
      biodegradation of organic compounds.

PMID- 8580643
TI  - Effect of carbon:nitrogen ratio on kinetics of phenol biodegradation by
      Acinetobacter johnsonii in saturated sand.
AB  - In polluted soil or ground water, inorganic nutrients such as nitrogen may be
      limiting, so that Monod kinetics for carbon limitation may not describe microbial
      growth and contaminant biodegradation rates. To test this hypothesis we measured
      14CO2 evolved by a pure culture of Acinetobacter johnsonii degrading 120
      micrograms 14C-phenol per ml in saturated sand with molar carbon:nitrogen (CN)
      ratios ranging from 1.5 to 560. We fit kinetics models to the data using non
      linear least squares regression. Phenol disappearance and population growth were
      also measured at CN1.5 and CN560. After a 5- to 10-hour lag period, most of the
      14CO2 evolution curves at all CN ratios displayed a sigmoidal shape, suggesting
      that the microbial populations grew. As CN ratio increased, the initial rate of
      14CO2 evolution decreased. Cell growth and phenol consumption occurred at both
      CN1.5 and CN560, and showed the same trends as the 14CO2 data. A kinetics model
      assuming population growth limited by a single substrate best fit the 14CO2
      evolution data for CN1.5. At intermediate to high CN ratios, the data were best
      fit by a model originally formulated to describe no-growth metabolism of one
      substrate coupled with microbial growth on a second substrate. We suggest that
      this dual-substrate model describes linear growth on phenol while nitrogen is
      available and first-order metabolism of phenol without growth after nitrogen is
      depleted.

PMID- 8580644
TI  - Anaerobic dechlorination of trichloroethene, tetrachloroethene and 1,2
      dichloroethane by an acetogenic mixed culture in a fixed-bed reactor.
AB  - An anaerobic enrichment culture with glucose as the sole source of carbon and
      energy plus trichloroethene (TCE) as a potential electron acceptor was inoculated
      with material from a full size anaerobic charcoal reactor that biologically
      eliminated dichloromethane from contaminated groundwater (Stromeyer et al. 1991).
      In subcultures of this enrichment complete sequential transformation of 10 microM
      TCE via cis-dichloroethene and chloroethene to ethene was reproducibly observed.
      Maintenance of this activity on subcultivation required the presence of TCE in
      the medium. The enrichment culture was used to inoculate an anaerobic fixed-bed
      reactor containing sintered glass Raschig elements as support material. The
      reactor had a total volume of 1780 ml and was operated at 20 degrees C in an up
      flow mode with a flow rate of 50 ml/h. It was fed continuously with 2 mM glucose
      and 55 microM TCE. Glucose was converted to acetate as the major product and to a
      minor amount of methane; TCE was quantitatively dehalogenated to ethene. When, in
      addition to TCE, tetrachloroethene or 1,2-dichloroethane were added to the
      system, these compounds were also dehalogenated to ethene. In contrast, 1,1,1
      trichloroethane was not dehalogenated, but at 40 microM severely inhibited
      acetogenesis and methanogenesis. When the concentration of TCE in the feed was
      raised to 220 microM, chloroethene transiently accumulated, but after an
      adaptation period ethene was again the only volatile product detected in the
      effluent. The volumetric degradation rate at this stage amounted to 6.2
      mumol/l/h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8580645
TI  - A rationale for the appropriate amount of inoculum in ready biodegradability
      tests.
AB  - Several screening methods at the so-called ready biodegradability level are
      suitable to test poorly soluble substances. Typical for these tests is that
      mineralization is evaluated from monitoring oxygen uptake or carbon dioxide
      production. Unfortunately, they suffer from a rather low precision in the
      calculated percentage of mineralization caused by subtracting a too high inoculum
      control measurement from the response in the test system. Criteria for blank
      oxygen consumption, due to the metabolic activity of the inoculum, are proposed
      from which maximum amounts of activated sludge or secondary effluent per litre
      test medium can be derived to be used as an appropriate inoculum. Both for
      current and future standardized tests the precision of the method can be kept
      within acceptable margins. Inoculum material was sampled from 40 communal
      biological waste water treatment plants. From endogenous respiration rates it was
      derived that the concentration of secondary effluent in the Closed Bottle Test
      can be increased up to 50 mL/L but that in respirometry tests inoculated with
      activated sludge the appropriate concentration is 10 mg/L dry matter or below,
      depending of the design of the test system.

PMID- 8580646
TI  - Biodegradation of the nitroaromatic herbicide dinoseb (2-sec-butyl-4,6
      dinitrophenol) under reducing conditions.
AB  - The degradation pathway for dinoseb (2-sec-butyl-4,6-dinitrophenol) under
      reducing conditions was investigated. Cultures were inoculated with a dinoseb
      degrading anaerobic enrichment culture used in field studies. Biotransformation
      intermediates were extracted with ethyl acetate and analyzed by high pressure
      liquid chromatography, gas chromatography, and mass spectrometry. Dinoseb
      degradation involves reduction of the nitro groups to amino groups followed by
      replacement with hydroxyl groups. Depending on the pH and redox potential in the
      culture, these intermediates may exist as quinones or hydroquinones.

PMID- 8580647
TI  - Simultaneous NH3 oxidation and N2 production at reduced O2 tensions by sewage
      sludge subcultured with chemolithotrophic medium.
AB  - The ammonia oxidation rate by sewage sludge was determined as a function of the
      dissolved oxygen tension. Samples of sludge were taken from a domestic waste
      water treatment pilot plant in which sludge was completely retained by membrane
      filtration. The samples were subcultured chemolithotrophically in recycling
      reactors. The gas supplied was a mixture of pure argon and oxygen. The KO2 for
      ammonia oxidation was estimated to be 0.97 (+/- 0.16) kPa dissolved oxygen.
      Together with ammonia oxidation and oxygen consumption, dinitrogen gas was
      produced. So, aerobic denitrification occurred. At dissolved oxygen tensions of
      1.25 kPa and higher, the dinitrogen production rate (per N-mole) equalled 20% of
      the ammonia oxidation rate. This proportion was even 58% at 0.3 kPa dissolved
      oxygen. At 0.15 kPa dissolved oxygen, however, nitrification hardly proceeded,
      while dinitrogen production soon stopped. Most likely, a nitrifier concomitantly
      oxidized ammonia and reduced nitrite to dinitrogen.

PMID- 8580649
TI  - Papers presented at the IXth World Congress on In Vitro Fertilization and
      Alternate Assisted Reproduction. Vienna, Austria, April 3-7, 1995.

PMID- 8580648
TI  - Bioethics in medically assisted conception in the Muslim world.

PMID- 8580650
TI  - Sex ratio of babies is unchanged after transfer of fast- versus slow-cleaving
      embryos.
AB  - PURPOSE: A higher proportion of male offspring has been observed after
      transferring faster-developing embryos in a number of animal species. Therefore,
      we evaluated the correlation between the sex ratio of delivered babies and the
      cleavage stage of transferred embryos in a human IVF-ET program. METHODS: The sex
      of infants born (n = 104) after transfer of exclusively slower-cleaving < or = 3
      cell (n = 41) versus exclusively faster-cleaving > or = 4 cell (n = 63) embryos
      was compared. Furthermore, all boys and girls resulting from IVF-ET (n = 213)
      were compared with respect to: the average number of cells in the embryos that
      were transferred, the embryo with the greatest number of cells in the cohort
      transferred and the percentage of embryos that were faster cleaving. RESULTS:
      Thirty seven percent (15/41) of infants resulting from the transfer of
      exclusively slower-growing embryos were girls and 38% (24/36) of the infants from
      the faster-growing embryos were girls (NS). The analysis all 213 babies born
      after 145 embryo transfer procedures did not suggest any differences in embryo
      cleavage rates in embryo transfers leading to male versus female infants.
      CONCLUSIONS: A greater number of boys born was not observed after transfer of
      faster-cleaving embryos as has been described in other animal species. The race
      to be male may not occur until later cleavage divisions or may not occur in the
      human embryo.

PMID- 8580651
TI  - Factors associated with improving success rates with gamete intrafallopian
      transfer under thin-needle spinal anesthesia.
AB  - PURPOSE: In order to reduce the risk of major anesthetic complications associated
      with laparoscopic gamete intrafallopian transfer procedures, we have exclusively
      used thin-needle spinal anesthesia over the years 1991 - 1994. This paper will
      review complication rates in order to further establish the safety profile of
      GIFT under thin-needle anesthesia and report the changes in our GIFT protocol
      from 1991 to 1994 which have been associated with a statistical improvement in
      the implantation rate from 11% to 23% (P = 0.01) and an increase in delivery
      rates from 29% to 42% per transfer procedure. METHODS: Sixty-eight laparoscopic
      GIFT procedures were done in women with at least one patent oviduct and failure
      to respond to less invasive treatment. Clinical variables were analyzed to
      determine if similar patient populations had been treated over the study period.
      RESULTS: The improved delivery rates and implantation rates could not be
      explained by patient selection. No major perioperative complications occurred.
      Minor perioperative complications and difficulties included one patient requiring
      general anesthesia, one patient developing a spinal headache which could be
      managed conservatively at home, and one patient requiring a minilaparotomy to
      complete the GIFT procedure. The more serious complications occurred as a result
      of the superovulation and multiple oocyte transfer rather than the surgical or
      anesthetic technique. These included two patients with severe ovarian
      hyperstimulation requiring hospitalization, and five delivered triplet
      pregnancies. Factors associated with improving success rates included
      improvements in semen and equipment preparation as well as an increase in the
      number of sperm transferred from 200,000 to 500,000. CONCLUSIONS: GIFT can be
      performed with relative safety under thin needle spinal anesthesia with high
      implantation and delivery rates if care is made to optimize sperm and equipment
      preparation. GIFT under thin-needle spinal anesthesia may be an attractive
      alternative for treatment of longstanding nontubal infertility in couples willing
      to take the risk of ovarian hyperstimulation and multiple pregnancy.

PMID- 8580652
TI  - Families created through ovum donation: a preliminary investigation of
      obstetrical outcome and psychosocial adjustment.
AB  - PURPOSE: This study attempted to obtain preliminary follow-up information
      regarding obstetrical outcomes and the psychosocial well-being of families
      created through the ovum donation. There is presently very little known about
      this population with respect to obstetrical care, health status of offspring,
      family and marital relationships of recipient couples, or how couples feel about
      having chosen ovum donation as a family-building option. RESULTS: Fifty-nine
      couples were initially surveyed and, ultimately, extensive information was
      obtained for 30 husbands, 31 wives, and 51 offspring. There was a very high
      percentage of cesarean section deliveries (81.6%), and although a few children
      experienced health problems at birth, they are all now in good health and
      developmental milestones are within normal limits. Information was also obtained
      about breast-feeding experiences, choice of donor (known [sister] or anonymous),
      reasons for choosing ovum donation over other parenting options, and the impact
      of this choice on marital and family relationships. Demographic data were also
      obtained. CONCLUSIONS: For many infertile couples, the long struggle to become
      parents culminated in a successful birth, and the experience of pregnancy seemed
      to meet a need to be both biological and psychosocial parents. In general,
      subjects were extremely cooperative with the investigation and they indicated a
      desire to learn as much as possible about the psychosocial status of families
      created through ovum donation. As the assisted reproductive technologies move
      rapidly into the 21st century, it now seems imperative that health and mental
      health professionals gain more knowledge about the impact of third party
      reproduction and the psychosocial adjustment and well-being of families created
      by this medical technology.

PMID- 8580653
TI  - In vitro fertilization in women age 40 and older: the impact of assisted
      hatching.
AB  - PURPOSE: To assess the impact of assisted hatching on in vitro fertilization
      (IVF) outcome in women age 40 and older. METHODS: A retrospective analysis was
      performed to compare 28 cycles of IVF without assisted hatching to 38 cycles of
      IVF with assisted hatching. All patients in both groups were age 40 or older and
      the mean age was similar. RESULTS: The delivery rate per oocyte retrieval was
      significantly higher in the assisted hatching group (18/38; 48%) compared to the
      nonhatched controls (3/28; 11%, P = 0.0003). The implantation rate of hatched
      embryos (40/175; 22%) was clearly enhanced, compared to the nonhatched embryos
      (7/126; 6%, P < 0.001). The fertilization rate, number of oocytes and the number
      of embryos per patient were comparable in the two groups. CONCLUSIONS: Assisted
      hatching dramatically improves embryonic implantation and term pregnancy rates in
      women age 40 and older undergoing IVF.

PMID- 8580654
TI  - A seasonal effect on pregnancy rates in an in vitro fertilization program.

PMID- 8580655
TI  - Interferon gamma and interleukin 10 levels in preimplantation embryo culture
      media.
AB  - PURPOSE: The aim of our study is to elucidate whether human oocytes/embryos
      secrete IFN gamma and/or IL-10 and whether the fertilization process depends on
      the balance between these cytokines. METHODS: A total of 142 embryo culture media
      from 24 patients were collected and the cytokine levels were tested with ELISA.
      RESULTS: IFN gamma and IL-10 were detectable in 40.1% and 29.6% of culture media
      respectively. The difference of IFN gamma and IL-10 levels in media from
      fertilized oocytes between day 1 and day 2 are significant (0.46 vs. 1.47 and
      34.2 vs. 12.7, respectively). However there was no significant difference between
      the IFN gamma levels of the media from fertilized and nonfertilized oocytes 0.46
      vs. 0.85 at day 1 and 1.47 vs 1.49 at day 2, as well as IL-10 levels 34.2 vs.
      30.9 at day 1 and 12.7 vs. 9.58 at day 2 respectively. CONCLUSIONS: Human
      preimplantation embryos secrete the cytokines IFN gamma and IL-10. No effect of
      these cytokines on fertilization process could be shown.

PMID- 8580656
TI  - Risk factors for ectopic pregnancy after in vitro fertilization and embryo
      transfer.
AB  - PURPOSE: To find the incidence of ectopic pregnancy (EP) in patients who
      conceived in the IVF-ET program, and risk factors affecting the occurrence of EP.
      METHODS: We analyzed the effects of the indication for IVF, type of ovarian
      stimulation (hMG + hCG vs. GnRH + hMG + hCG), type of embryo transfer
      (transcervical intratubal, intrauterine in chest-knee position and intrauterine
      in lithotomy position) and number of embryos transferred on the occurrence of EP.
      EP was treated by laparotomy, prostaglandin E2 or laparoscopic surgery. RESULTS:
      In 7991 stimulated and 92 natural cycles treated in the Ljubljana IVF-ET program
      between May 1983 and June 1994 we achieved 1059 pregnancies, of which 44 were
      ectopic (incidence 4.1%), the main risk being tubal factor infertility. There
      were 38 (86.3%) tubal, 3 (6.8%) heterotopic, 1 (2.4%) ovarian, and 2 (4.5%)
      cornual EP. In two patients multiple tubal EP occurred (1 twin, 1 triplet). Forty
      two patients (95.4%) had tubal factor infertility, 1 (2.3%) unexplained, and 1
      (2.3%) patient had male factor. The incidence of EP in patients with tubal
      infertility was 5.4%, in patients with unexplained infertility 2.0% and in those
      with male factor 0.9%. There appeared to be no correlation between the two
      superovulatory methods. With transcervical intrauterine ET the incidence of EP
      was 0 of 5 clinical pregnancies (CP); with intrauterine in chest-knee position it
      was 26 (3.5%) of 738 CP; with intrauterine in lithotomy position it was 17 (5.4%)
      of 316 CP. The difference between the two types of intrauterine ET is not
      statistically significant. The incidence of EP did not correlate with the number
      of embryos transferred. The average initial values of beta hCG performed 17 days
      after ET were significantly lower in patients with EP than in those with normal
      singleton pregnancy (157 +/- 143 mIU/ml vs. 408 +/- 148 mIU/ml). CONCLUSIONS: EP
      can complicate the IVF procedure. The main risk factor is tubal infertility with
      or without previous tubal surgery. The low initial value of beta hCG has a strong
      predictive value in the diagnosis of EP.

PMID- 8580657
TI  - Antiovarian antibodies and their effect on the outcome of assisted reproduction.
AB  - PURPOSE: To compare the presence in levels of antiovarian antibodies (AOAb) in
      the pre- and postovulatory stage from serum of infertile patients undergoing
      intrauterine insemination (IUI) or in vitro fertilization (IVF) with outcome of
      the procedures. RESULTS: Serum from 36 women undergoing IUI, 36 women undergoing
      IVF and 25 fertile, healthy controls were assayed for the presence of AOAb by a
      commercially available ELISA kit. AOAb was positive in 59.7% of infertile women,
      while none of the fertile controls were positive for AOAb. The levels of these
      antibodies increased as the patient age and the number of treatment attempts
      increased. Though the presence of AOAb did not affect oocyte recovery rate, it
      resulted in decreased fertilization rate, cleavage rate, and pregnancy rate in
      infertile women. CONCLUSIONS: Our studies suggest that AOAb may be a cause of
      infertility and presence of these antibodies could have adverse effects on the
      outcome of assisted reproductive techniques.

PMID- 8580658
TI  - High rates of perforation are found in endovaginal ultrasound probe covers before
      and after oocyte retrieval for in vitro fertilization-embryo transfer.
AB  - OBJECTIVES: To study perforation rates of sterile transvaginal ultrasound probe
      covers before and after oocyte retrieval (OPU) in an IVF-ET program. METHODS:
      Transvaginal ultrasound probe sheaths from two different manufacturers were
      studied, Cook Innoray (Cook-Canada #TTUPS-100) and Swemed Lab (Frolunda Sweden
      #715). After controlled ovarian stimulation, OPU was done using the needle guide
      of a sterile sheathed 5-MHz transvaginal ultrasound transducer (ATL Bothell,
      Washington, USA). A newer designed Cook probe cover supplied by the manufacturer
      was also tested after the company was made aware of our initial perforation
      results. Following each OPU, probe covers were examined for perforations by
      filling them with water and checking for leaks. If perforations were found, the
      vaginal transducer was disinfected by soaking for 20 min in 2% gluteraldehyde
      (Formac). Twenty unused sterile probe covers from each manufacturer were also
      tested for perforations. RESULTS: After OPU we found 10/13 (75%) old Cook, and
      35/43 (81%) Swemed probe covers to be perforated (NS). Only 5/20 (25%) of the new
      design Cook probe covers were perforated post OPU (p = 0.000005). Analysis of
      unused probe covers revealed 13/20 (65%) Cook, and 5/20 (25%) Swemed probe covers
      to be perforated (P = 0.02). None of 10 new design unused Cook probe covers were
      perforated before use.

PMID- 8580659
TI  - Ureaplasma urealyticum and Mycoplasma hominis detected by the polymerase chain
      reaction in the cervices of women undergoing in vitro fertilization: prevalence
      and consequences.
AB  - PURPOSE: The prevalence of Ureaplasma urealyticum and Mycoplasma hominis in the
      endocervix at the time of oocyte collection in women undergoing in vitro
      fertilization (IVF) was examined using the polymerase chain reaction (PCR).
      METHODS: All women were treated with tetracycline following sample collection.
      RESULTS: U. urealyticum was identified in 56 (17.2%) of 326 women while M.
      hominis was present in only 5 (2.1%) of 235 women. U. urealyticum was detected at
      a higher frequency (P = 0.01) in those women whose IVF cycle failed prior to
      embryo transfer. This organism was present in 8 of 19 (42.1%) women with either
      no fertilization or no embryo transfer, 19 of 148 (12.8%) who had no evidence of
      pregnancy following embryo transfer, 6 of 30 (20.0%) who had only a transient
      (biochemical) pregnancy, 5 of 14 (35.7%) with a spontaneous abortion, and 18 of
      115 (15.6%) with a term birth. Of the eight women with U. urealyticum who had no
      embryos transferred, male factor was the cause of infertility in five cases, two
      women had tubal occlusions while in one woman the diagnosis was idiopathic.
      Therefore, poor sperm quality, and not a U. urealyticum infection, might explain
      the failure of most of these cases to proceed to the stage of embryo transfer.
      Analysis of all patients revealed no association between male factor infertility
      and U. urealyticum in the cervix. CONCLUSIONS: U. urealyticum, but not M.
      hominis, is present in the cervices of many culture-negative women. Its presence,
      however, does not influence IVF outcome subsequent to embryo transfer in women
      treated with tetracycline after oocyte retrieval.

PMID- 8580660
TI  - Pituitary down-regulation in IVF cycles: is it necessary to use strict criteria?
AB  - PURPOSE: In a retrospective study we have reviewed the data of 570 consecutive
      IVF cycles in which a GnRH agonist (GnRHa) was started in the early follicular
      phase (long protocol). Cycles were divided in groups according to estradiol
      levels before HMG administration: A, < 20 pg/ml; B, 20 to 50 pg/ml; C, 51 to 100
      pg/ml. Our objective was to determine if the degree of pituitary suppression had
      any effect on the ovarian response to stimulation by exogenous gonadotropins,
      and/or on the IVF outcome. RESULTS: There were no significant differences in
      cycle cancellation rates, no. of days of stimulation and ampoules of HMG, serum
      estradiol after HMG, no. of oocytes retrieved and fertilization rates between
      groups. Pregnancy rates (19.4%, 21% and 31.8%/cycle, and 24.1%, 27.5% and 37.8% /
      embryo transfer, respectively) and live-birth rates (16.2%, 16.1% and
      25.0%/cycle, 20.1%, 21.2% and 29.7%/embryo transfer, respectively) were also not
      significantly different. CONCLUSIONS: The degree of pituitary suppression had no
      effects on either the ovarian response to gonadotropins (including HMG
      requirements) or the overall IVF results.

PMID- 8580661
TI  - Morphology in intracytoplasmic sperm injection: preliminary results.
AB  - PURPOSE: Direct intracytoplasmic sperm injection (ICSI) is a successful treatment
      of severe male subfertility. Conventional in vitro fertilization shows poor
      pregnancy rates especially in cases of severe teratozoospermia. The objective was
      to determine if severe morphological defects of spermatozoa in
      oligoasthenoteratozoospermia (OAT) have any impact on the fertilization process
      in ICSI and if there are any specific morphological characteristics in
      nonfertilized oocytes after the ICSI procedure. METHODS: Ejaculates and
      nonfertilized oocytes were investigated by electron microscopy. CONCLUSIONS: The
      lack of intracytoplasmic sperm-oocyte interaction, not severe sperm defects,
      displays the most critical role in the fertilization process. Clinical data with
      fertilization rates of 66% and pregnancy rates of 23.3% confirm the fertilization
      capacity of severely

PMID- 8580662
TI  - Fertilization and pregnancies following intracytoplasmic injection of testicular
      spermatozoa.
AB  - PURPOSE: Intracytoplasmic injection (ICSI) with testicular sperm was performed in
      16 couples. All men had ductal obstruction and failed previous attempts of
      epididymal sperm microaspiration. METHODS: Testis tissue was obtained by
      excisional biopsies and incubated in HEPES buffered EBSS medium over 24 h at 37
      degrees C. Motile sperm (Grade 1 to 2) were recovered in 13 patients and
      fertilized a total of 62 oozytes. Four pregnancies were achieved. RESULTS: One
      healthy boy and two girls (twin pregnancy) were born. CONCLUSIONS: The ongoing
      pregnancies revealed no fetal abnormalities on ultrasound scanning.

PMID- 8580663
TI  - Ultrastructure of endometrial epithelial cells in a three-dimensional cell
      culture system for human implantation studies.
AB  - PURPOSE: A three-dimensional cell culture system imitating normal uterine
      endometrium has previously been established. To what degree do cultured
      epithelial cells retain their morphological characteristics as compared to in
      vivo material obtained simultaneously from the same tissue donor. RESULTS: We
      found a high degree of similarity between the in vivo and in vitro situations.
      The present culture system furthermore imitates the day-to-day morphology of the
      cycle. CONCLUSIONS: This indicates, that a correct timing of the biopsy tissue is
      important for future human implantation studies.

PMID- 8580664
TI  - Regulation of IGF binding proteins by FSH in human luteinizing granulosa cells.
AB  - OBJECTIVE: To evaluate the regulation of the secretion of insulin-like growth
      factor (IGF) binding proteins (IGFBPs) by FSH in human luteinizing granulosa
      cells. DESIGN AND RESULTS: Luteinizing granulosa cells were incubated with and
      without FSH. Levels of IGFBP-1 and -3 in the medium were measured by EIA and RIA,
      respectively and binding activities of these IGFBP were evaluated by Western
      ligand blot. FSH inhibited the secretion of IGFBP-1 dose dependently. FSH did not
      inhibit the secretion of immunoreactive IGFBP-3, but inhibited the binding
      activity of IGFBP-3. To assess the protease activity, 125I-IGFBP-3 was incubated
      with the cultured medium. 125I-IGFBP-3 degraded into small fragments when it was
      incubated with the cultured medium treated with FSH. CONCLUSIONS: FSH enhances
      the action of IGF-I in human granulosa cells by inhibiting the secretion of IGFBP
      1 and the binding activity of IGFBP-3 by stimulating the proteolysis of IGFBP-3.

PMID- 8580665
TI  - Influence of elevated pH levels on structural and functional characteristics of
      the human zona pellucida: functional morphological aspects.
AB  - PURPOSE: A total of 86 fresh and salt-stored immature human oocytes derived from
      postmortem ovarian tissue were used for this study. METHODS: Oocytes were
      randomly incubated either in synthetic human tubal fluid medium (untreated zonae)
      or in a chemically defined medium (treated zonae). RESULTS: Sperm binding
      experiments using hemizona assay conditions exhibited a 10-fold increased binding
      of sperm to treated compared to untreated oocytes (272.7 +/- 43 versus 24.3 +/-
      15 sperm bound, respectively; P < 0.0001). pH recordings during incubation showed
      elevated pH levels of 8.1 compared to pH 7.2 among treated and untreated zonae,
      respectively. Ultrastructural examination showed a spongy appearance of the
      surface of treated zonae, whereas untreated zonae appeared compact with smooth
      surface. CONCLUSIONS: The marked increase in sperm binding among treated zonae,
      together with the ultrastructural findings, suggest that the altered zona surface
      enhances sperm binding. The physiological maturational process of the zona
      pellucida might be manipulated in vitro, thus increasing sperm binding to the
      zona.

PMID- 8580666
TI  - Influence of follicular phase duration on human granulosa-luteal cell
      subpopulations in natural and stimulated IVF-ET cycles.
AB  - OBJECTIVES: To observe the granulosa-luteal cell subpopulations presented within
      follicular aspirates concerning duration of the follicular phase and the type of
      IVF protocol. DESIGN: Cells were obtained from dominant follicles of 40 women
      with natural IVF-ET cycles, in which preovulatory hCG was given when the follicle
      was mature, and from 40 follicles of 32 women with hMG and hCG stimulated IVF-ET
      cycles. Granulosa-luteal cell subpopulations were observed by computerized image
      analysis in which hCG was localized using immunoperoxidase staining. RESULTS: (1)
      The nonluteinized granulosa cells from natural developing follicles were larger
      than those from stimulated ones regardless of the follicular phase duration. (2)
      The size of each luteinized cell subpopulations was influenced neither by the two
      IVF protocols nor by the follicular phase duration. (3) The hCG stained cells
      from natural developing follicles were larger than the ones from stimulated
      follicles and their relative number in aspirates was higher. Cell areas and
      distribution were not influenced by the duration of follicular phase. (4) In
      stimulated conditions, hCG stained cells became larger if follicular phase was
      longer. CONCLUSIONS: Duration of the follicular phase influences the
      immunocytochemical hCG localization and the morphometric characteristics of
      granulosa-luteal cell subpopulations presented within natural developing
      follicles and stimulated ones.

PMID- 8580668
TI  - Successful delivery at age 61: report of a case as a result of oocyte donation.

PMID- 8580667
TI  - Bacterial contamination after transvaginal aspiration (TVA) of oocytes.

PMID- 8580669
TI  - Adrenaline and its receptors: one hundred years of research.
AB  - One hundred years ago, Oliver and Schafer reported that crude extracts from the
      adrenal medulla produced marked physiological effects. It was the birth of
      adrenaline for biomedical research. The purpose of this review is to commemorate
      the 100th Anniversary of this discovery by briefly presenting to the readers a
      historical account of the major discoveries and some current ideas on the actions
      and mechanisms of action of this hormone and neurotransmitter.

PMID- 8580670
TI  - Patterns of recurrence in squamous cell carcinoma of the anal canal.
AB  - The objective of the study was to identify the patterns of recurrence in patients
      with squamous cell carcinoma of the anal canal (SCCAC) vs. the size of the
      primary tumor and its further possible impact on its treatment outcome. We
      reviewed 78 patients treated between 1975 to 1991. They were classified according
      to to the AJC/UICC classification. From 1975 to 1985, 16 patients were treated
      with radical surgery (RS). From 1985 to 1991, 43 patients were treated with
      radiotherapy (RT) at doses of 45 Gy/4-5 weeks, to the pelvis and a boost of 15-30
      Gy to the perineum. Since 1989, in 19 selected patients, 5-FU and mitomycin-C
      have been added to the RT schedule (C-RT). There were 55 females and 23 males.
      The overall recurrence rate was 62%. In T1 tumors, no recurrences occurred. The
      local recurrence (LR) according to treatment approach and T were: radical
      surgery: T2, 50%; T3, 71%; T4, 100%. Radiation therapy: T2, 25%; T3, 41%; T4,
      66%. Chemoradiation therapy: T2, 12%; T3, 40%; T4, 50%. Regional recurrences were
      in RS: T2, 16%; T3, 28%; T4, 100%. RT: T2, 0%; T3, 16%; T4, 33%. C-RT: T2, 0%;
      T3, 20%; T4, 25%. Distant recurrences were in RS: T2 and T3, 0%; T4, 66%. In RT:
      T2, 0%; T3, 8%; T4, 33%. In C-RT: T2, 0%; T3, 8%; T4, 50%. In T1 patients, no
      recurrences were observed. In T2 tumors the recurrence pattern was local. In T3
      tumors it was locoregional and to the groin area. In T4 tumors it was
      locoregional and distant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8580671
TI  - Portal-systemic encephalopathy and gastrointestinal bleeding after
      cardioselective beta-blocker (metoprolol) administration to patients with portal
      hypertension.
AB  - The use of the non-selective beta-blocker propranolol has been widely recommended
      to prevent gastrointestinal bleeding in patients with portal hypertension. We
      conducted a prospective, randomized controlled trial of metoprolol, a selective
      beta-blocker for prevention of gastrointestinal bleeding from portal hypertension
      in 29 non-selected patients with liver disease and previous gastrointestinal
      bleeding. Fifteen patients received placebo treatment for 40 +/- 18 months and 14
      patients received metoprolol for 31 +/- 17 months. A sustained reduction in
      resting pulse was observed in those patients treated with metoprolol. There was
      no significant difference in acute re-bleeding episodes between the two groups.
      Of the 14 patients treated with metoprolol, three (21%) re-bled, all three
      requiring blood transfusion. Four (26.5%) of the 15 patients treated with the
      placebo re-bled, two cases with acute bleeding and the remaining two cases
      presented a positive stool guaiac test. All cases who bled during the metoprolol
      therapy required exclusion from the trial, and surgical procedures or
      sclerotherapy as well. After both metoprolol or placebo treatments, similar
      deterioration of standard liver function tests was observed. Further, at the end
      of the trial, 11 patients on metoprolol (78%) and four of the patients treated
      with the placebo (27%) required treatment for clinical portal-systemic
      encephalopathy (p < 0.01). The risk of poor sympathomimetic response after
      cardioselective beta 1-blocker during acute bleeding episodes and the appearance
      of hepatic encephalopathy deserve further investigation. The selective beta
      blocker metoprolol seems to be an inadequate choice to prevent gastrointestinal
      re-bleeding in patients with portal hypertension.

PMID- 8580672
TI  - Face immersion reflex for diagnosis of diabetic cardiovascular autonomic
      neuropathy.
AB  - To evaluate face immersion reflex (FIR) as a diagnostic test for diabetic
      autonomic neuropathy, we studied 15 patients with diabetic cardiovascular
      autonomic neuropathy--defined as the presence of at least two other abnormal
      autonomic tests-and 15 healthy subjects as a control group. All patients
      underwent six different autonomic tests including deep breathing R-R variation,
      Valsalva maneuver, heart rate and blood pressure response to standing,
      intravenous atropine injection and FIR. FIR test was considered positive for
      autonomic neuropathy if heart rate did not decrease at least 15% of the basal
      rate after 10 sec of immersion. FIR was positive in all the diabetic patients and
      negative in the 15 controls. Its sensitivity was higher than any other single
      autonomic test (p < 0.025). Considering two abnormal autonomic tests as a gold
      standard for diabetic cardiovascular autonomic neuropathy, sensitivity was 100%
      for FIR, 66% for deep breathing R-R variation and Valsalva maneuver, 53% for
      blood pressure (BP) response to standing and 20% for i.v. atropine injection. All
      the test were highly specific. We conclude FIR test should be considered among
      diagnostic tests for diabetic cardiovascular autonomic neuropathy.

PMID- 8580673
TI  - Myocardial infarction in a low income area of Mexico City. Prevalence and
      clinical characteristics.
AB  - We present the results of a population based survey (The Mexico City Diabetes
      Study) in which the prevalence of myocardial infarction (MI) was estimated in
      2282 subjects using Minnesota coded electrocardiograms (ECG). Participating
      individuals were men (941) and non-pregnant women (1341) between 35-64 years of
      age, residing in a low income area of Mexico City. Electrocardiograms were
      classified in three categories: definitive MI (pathological Q and QS patterns,
      all 1.1 codes) and prominent Q and QS patterns accompanied by negative T waves
      (all 1.2 codes accompanied by code 5.1 or 5.2 with the exception of 1.2.6. and
      1.2.8.). Possible MI included minor Q and QS patterns (all 1.3 codes and codes
      1.2.6. and 1.2.8.) and unlikely MI included all other codes. Two tracings were
      uncodeable (final n = 2280), ten ECGs were classified as "definitive", 39 met
      criteria for "possible". Due to the small number, both categories, definitive and
      possible were combined. The overall prevalence of MI was higher in men (3.2%)
      than women (1.4%). In men ECG evidence of a MI was associated with older age,
      higher systolic blood pressure, higher 2-h post-glucose challenge and higher
      fasting and post-glucose challenge insulinemia. No corresponding associations
      were observed in women although the number of events in women was small. The
      prevalence of MI in Mexico City appears to be lower than that observed in some
      Mexican-American populations in the southern U.S. where prevalence for men was
      estimated around 4% and for women 2.5% for the same age group.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8580674
TI  - Patients with TSH-secreting pituitary tumor possess different TSH molecular
      isoforms.
AB  - The objective of the study was to demonstrate if TSH secreted by a pituitary
      tumor correlates with particular molecular forms of TSH. Aliquots of sera from
      two hyperthyroid patients with TSH-secreting pituitary tumor were subjected to
      gel filtration chromatography to be assayed for TSH. The assay was repeated in
      one case after transsphenoidal adenomectomy. Sera from two additional patients
      with long-lasting primary hypothyroidism, and from two subjects with normal
      thyroid function were also chromatographed. Molecular weight (mol wt) of isoforms
      was calculated on a calibration curve obtained with molecular markers. The
      molecular variants were characterized on the basis of elution volume, mol wt, and
      partition coefficient. Chromatographic profile of the two cases with TSH
      secreting pituitary tumor exhibited mainly two peaks of TSH immunoreactivity. The
      major component of immunoreactivity eluted as a peak corresponding with the alpha
      subunit of the glycoprotein. This pattern was different from that obtained in
      sera from two women with hypothyroidism, which was heterogeneous and presented a
      predominance of molecular variants corresponding with mol wt of 22 and 29 kD, and
      no alpha-subunit was present. In cases of normal thyroid function the
      chromatographic profile showed that the major proportion of TSH eluted
      simultaneously with the labeled standard and 22 kD marker. These results
      demonstrate that TSH secreted by pituitary tumors is composed of various
      molecular forms and the alpha-subunit is the major component. This
      chromatographic profile is different from that observed in other cases with
      elevated concentrations of TSH as it occurs in primary hypothyroidism.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8580675
TI  - Univariate and multivariate analysis of risk factors for ovarian cancer: case
      control study, Mexico City.
AB  - Female residents of the southern part of Mexico City diagnosed with epithelial
      ovarian cancer between 1989 and 1992 (n = 172) were interviewed regarding
      reproductive events. The same information was obtained from the controls (n =
      441). There was an elevated risk for ovarian cancer associated with an increased
      number of abortions, relative risk = 3.66 (95% confidence interval = 1.02 -
      13.45) for women with four fetal losses. Ovarian cancer risk was shown to
      decrease as parity increased, reaching a relative risk of 0.23 (95% confidence
      interval = 0.09 - 0.55) in women with four or more live births in the
      postmenopausal group. This negative association seems less evident in overall
      cases. Logistic regression methods were used and abortions and high estimated
      number of ovulatory cycles were found to be associated with an increased risk of
      ovarian cancer. The inclusion of nonreproductive variables such as educational
      status, in the logistic model, showed that cases had a lower educational level
      than that of controls.

PMID- 8580677
TI  - Simultaneous growth and mass encystation of Entamoeba invadens under axenic
      conditions.
AB  - Encystation of Entamoeba invadens IP-1 strain trophozoites was induced in low
      glucose medium (LG). The numbers of trophozoites, cysts and nuclei per cyst were
      determined; excystation of detergent-resistant axenic cysts was induced in both
      BI-S-33 and LG media. It was found that after 48 and 72 h of incubation in LG,
      cyst production was higher than trophozoites inoculated, 90 and 65% of those
      cysts being morphologically viable, respectively, as differentiation proceeded
      cysts became tri- and tetranucleated.E. invadens cysts were able to excyst either
      in BI-S-33 or LG media. There were no differences in growth kinetics when amebic
      cultures from cysts excysted in BI-S-33 were compared with parent strain. On the
      contrary, lower yields of trophozoites were achieved with amebas excysted and
      further cultured in LG medium, but they were able to grow and simultaneously
      undergo mass encystation. This, as well as other evidence, suggests that E.
      invadens trophozoites are able to modulate their physiology according to the
      nutrients and other factors available in the medium, in order to accomplish,
      growth, encystation or simultaneous growth and mass encystation. Induction of
      life cycle of pathogenic amebas under axenic conditions can provide answers to
      inhibit encystment and/or excystment.

PMID- 8580676
TI  - A comparative study of the effects of some 5-HT1A receptor agonists on the blood
      pressure of pithed rats.
AB  - The intention of this study was to supply additional information about direct
      effects of the 5-HT1A receptor agonist indorenate on the arterial blood pressure.
      The effects of indorenate were compared with those of buspirone and ipsapirone
      (all selective 5-HT1A agonists) on the blood pressure of pithed rats. These
      compounds increased the blood pressure in a dose-dependent fashion. The effects
      of either ipsapirone or buspirone were clearly inhibited with 100 micrograms/kg
      of prazosin (selective alpha 1-adrenoceptor antagonist), whereas 1 mg/kg of this
      blocker elicited only a mild inhibition of the pressor effect of indorenate.
      Pindolol (100 micrograms/kg; a beta-adrenoceptor and 5-HT1 receptor blocker) was
      unable to modify the effects of all the 5-HT1A agonists tested. In addition, the
      5-HT2 receptor and weak alpha 1-adrenoceptor blocker ketanserin (10-100
      micrograms/kg) antagonized the pressor effect of indorenate. Nevertheless, only a
      mild inhibition was observed in the case of both ipsapirone and buspirone. On the
      other hand, the latter drugs diminished the blood pressure of pithed rats
      intravenously infused with norepinephrine, but indorenate was inactive. However,
      in rats infused with quipazine, all the 5-HT1A agonists failed to reduce blood
      pressure. These results indicate that buspirone and ipsapirone behaved as partial
      alpha 1-adrenoceptor agonists. Furthermore, the results show that indorenate
      elicited pressor effects are probably due to stimulation of 5-HT2 receptors.
      Thus, unlike ipsapirone and buspirone, indorenate did not show conclusively
      activity related with alpha 1-adrenoceptors.

PMID- 8580678
TI  - Molecular detection of Brucella spp.: rapid identification of B. abortus biovar I
      using PCR.
AB  - Brucellosis is an important zoonotic disease caused by several species of the
      genus Brucella. The most reliable diagnostic tests are based on microbiological
      analysis, bacterial growth, and biochemical reactions which are cumbersome and
      represent a risk of infection for technicians performing them. Recently, safe
      molecular genetic techniques have been incorporated in studies regarding taxonomy
      and evolution of Brucella. The polymerase chain reaction (PCR) was used here to
      analyze a duplicated gene (omp 2) encoding an outer membrane protein in members
      of the genus Brucella. The developed procedure detects each of the five species
      herein tested and their biovars: B. abortus, B. suis, B. melitensis, B. canis and
      B. ovis. It also permits the detection of an approximately 115 bp deletion in the
      omp 2a gene, consistently found in five different strains of B. abortus biovar 1:
      vaccine strain S19, rough mutant RB51, reference strains 544 and A99, and a
      strain isolated from naturally infected bovines.

PMID- 8580679
TI  - The opioid system and excitatory amino acids in the onset of puberty in female
      rats.
AB  - The control of sexual maturation by the hypothalamus is incompletely understood.
      The activation and/or removal of inhibition of gonadotropin-releasing hormone
      (GnRH) secretion at puberty involves several neurotransmitters. Excitatory amino
      acids (EAA), such as L-glutamic acid (L-GLU), may increase gonadotropin secretion
      acting on N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Endogenous opiates
      peptides (EOP) play an inhibitory role on gonadotropin secretion, and the opiate
      antagonist naloxone (NAL) increases serum LH levels. We tested the effect of
      drugs acting on the opiate and EAA systems. We treated prepubertal rats with
      intraperitoneal injections of NAL, NMDA antagonist dextromethorphan (DMT) and non
      NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX), alone and in
      combinations among them. The onset of puberty was assessed by the vaginal opening
      (VO). Female Wistar rats (25 days old), weaned at 21 days of age, were randomly
      assigned to one of seven groups (15 rats each). The groups were treated with 1)
      DMT (18 mg/kg b.w.), 2) DNQX (17 micrograms/kg), 3) NAL (0.5 mg/kg), 4) NAL plus
      DMT, 5) NAL plus DNQX, 6) DMT plus DNQX and 7) control vehicle: distilled water).
      The age at VO among groups was significant by survival time analysis (x2 = 15.18,
      p = 0.018). Analysis of covariance controlling for weight and length at 21 days
      showed that the groups treated with NAL alone (p = 0.003) or combined with DMT (p
      = 0.012) and DNQX (p = 0.005) had earlier age at VO. NMDA and non-NMDA antagonist
      used alone or combined were not different from the control group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8580680
TI  - Extraction and partial characterization of a low molecular weight collagenase
      from normal rat kidney.
AB  - A matrix metalloproteinase with selective affinity for collagen was identified
      and partially purified from normal rat kidney. A two-step purification procedure
      consisting of gel filtration and affinity chromatography on Sepharose 4B-collagen
      resulted in an increase in specific activity of more than 3,000 times. The
      partially purified collagenase cleaved type I collagen and also showed low
      gelatinolytic activity. The enzyme required Ca2+ and revealed a neutral pH
      optimum; it was not inhibited by thiol or serineprotease inhibitors. Its activity
      was fully blocked using recombinant tissue inhibitor of metalloproteinases-1.
      Using SDS-PAGE and zymography, the estimated Mr of the collagenase was 16.5 x
      10(3).

PMID- 8580681
TI  - Two Trichomonas vaginalis surface proteinases bind to host epithelial cells and
      are related to levels of cytoadherence and cytotoxicity.
AB  - Recent reports strongly suggest that cytoadherence and cytotoxicity by
      Trichomonas vaginalis require cysteine proteinase activity. Because of the large
      number of cysteine proteinases synthesized by T. vaginalis, a ligand assay was
      used to identify specific proteinases which may selectively target host cells.
      Two cysteine proteinases from trichomonal extracts with relative molecular masses
      (Mr) of 65,000 daltons (65-kDa) and 30-kDa were found to avidly bind to HeLa cell
      and vaginal epithelial cell surfaces. The two proteinases were distinguished by
      differential inhibition with leupeptin and N-alpha-p-tosyl-L-lysine chloromethyl
      ketone (TLCK). Leupeptin pretreatment of live organisms inhibited the 30-kDa
      proteinase, which concomitantly reduced or eliminated cytoadherence. The T.
      vaginalis isolates with low levels of cytoadherence also had diminished or no
      detectable 30-kDa proteinase activity. On the other hand, TLCK pretreatment
      inhibited both the 30-kDa and 65-kDa proteinases, which resulted in decreased
      levels of cytoadherence and totally abolished contact-dependent cytotoxicity.
      Furthermore, isolates capable of attachment but with little or no cytotoxicity
      toward HeLa cells had no detectable host cell-bound 65-kDa proteinase. Finally,
      antiserum generated to each proteinase reacted by indirect immunofluorescence
      with live organisms, suggesting a surface location for both proteinases. This
      strategy and use of the ligand assay may permit for the deliniation of the role
      of two specific T. vaginalis surface proteinases in the properties of
      cytoadherence and cytotoxicity.

PMID- 8580682
TI  - Use of molecular biological techniques in the diagnostic laboratory for detecting
      and differentiating fungi.
AB  - This review will address the value of nucleic acid amplification techniques used
      for the laboratory diagnosis of fungal infections. Although detection of all
      fungi will be considered, the emphasis will be placed on diagnosis of
      disseminated candidiasis. The diagnosis of most serious life threatening fungal
      infections in immunosuppressed patients remains a laboratory dilemma. The
      antemortem diagnosis of disseminated candidiasis, if made at all, is often made
      just prior to the death of the patient negating any hope of successful
      medical/surgical intervention. Molecular techniques such as those based on the
      polymerase chain reaction offer increased sensitivity since, in theory, these
      techniques require the presence of a single fungal cell. This manuscript will
      review 1) the current problems related to classical methods of diagnosing life
      threatening fungal infections; 2) considerations one must address relative to use
      of nucleic acid-based approaches such as polymerase chain reaction (PCR) for
      diagnosis of these fungal infections; and 3) status of use of these molecular
      approaches in the clinical mycology laboratory at the present time.

PMID- 8580683
TI  - Molecular genetics and the diagnostic mycology laboratory.
AB  - The laboratory diagnoses or confirmation of fungal diseases are extremely
      important considerations in the proper and efficient management of patients
      experiencing these infections. When an infectious process is suspected, suitable
      material must be collected and submitted to the pathologist for microscopic
      examination and to the diagnostic laboratory for culture. The practice of modern
      medicine dictates that the turn-around time be reduced to a minimum so that
      specific therapy can be rapidly instituted. Unfortunately, the classical
      procedures used in processing specimens for isolation and identification of fungi
      implicated in these diseases are technically time consuming and on occasion labor
      intensive. More importantly, fungi are slow growing and cultures are frequently
      held for 3 to 4 weeks before they are discarded as negative. With the exception
      of coccidioidomycosis, most attempts to develop serological tests for rapid
      diagnosis of fungal infections have been hampered by poor specificity caused by
      immunologic cross reactivity. To some extent, such problems can be circumvented
      by application of molecular biological techniques to these problems. For example,
      procedures have been developed that allow efficient screening of DNA expression
      libraries to identify useful recombinant antigens and production of selected
      antigens in quantity. This is potentially a practical approach using molecular
      biological techniques for development of sensitive, specific and practical
      reagents useful in the serological diagnosis of fungal infections. In addition,
      nucleic acid hybridization techniques based on the ability of complementary
      nucleic acid strands to specifically align and associate to form stable double
      stranded complexes have been put to use to develop confirmation tests for a
      variety of important fungal isolates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8580684
TI  - Biochemistry and molecular biology of the main diagnostic antigen of
      Paracoccidioides brasiliensis.
AB  - The 43,000 dalton glycoprotein of Paracoccidioides brasiliensis (gp 43) is the
      main exocellular antigen recognized by sera from patients with
      paracoccidioidomycosis in a variety of serological assays. Specific
      conformational peptide epitopes are recognized by the human antibodies as
      determined by antigen deglycosylation. Procedures for the purification of the
      gp43 using immunoaffinity chromatography have been described. The secretion of
      the gp43 as a function of the growth curve, its partial aggregation with a
      proteolytic enzyme, ability to bind laminin, as well as to form circulating
      immunocomplexes in vivo could play a role in pathogenesis. Crude antigenic
      preparations depleted of gp43 epitopes lost their ability to elicit positive skin
      tests. Accordingly, the purified gp43 molecule induced delayed hypersensitivity
      reactions in man and infected animals, caused a T-CD4-dependent proliferation of
      lymph node cells from mice immunized with it, and of peripheral blood lymphocytes
      from an individual sensitized to P. brasiliensis by prolonged contact with the
      fungus. To identify the immunodominant epitopes in both humoral and cellular
      reactions, the gp43 gene has been cloned, sequenced, and partly expressed. It
      bears peptide sequences homologous to those of beta-1,3-glucanases from Candida
      albicans and Saccharomyces cerevisiae but has no enzymatic activity itself. The
      molecular weight of the unglycosylated antigen is 42,227. A single N-linked
      oligosaccharide chain in the gp43 contains alpha-D-mannopyranosyl, beta-D
      galactofuranosyl and N-acetylglucosaminyl units with the predominant ratio of
      10:2:2, and characteristics of a high mannose type.

PMID- 8580685
TI  - In search of the natural habitat of Paracoccidioides brasiliensis.
AB  - Paracoccidioides brasiliensis (Pb) is the dimorphic fungus responsible for
      paracoccidioidomycosis (PCM), one of the most important systemic mycosis in Latin
      America where the disease is geographically restricted. The natural habitat of
      the causative agent remains undetermined. We are planning to use PCR-based
      technology in order to amplify specific DNA fragments. The high sensitivity of
      this technique may allow us to detect the natural habitat of Pb. In this study,
      we prepared a cDNA library from which we cloned a protein of approximately 27 kDa
      MW. When this recombinant antigenic protein was tested by the immunoblot
      technique, it was able to recognize antibodies in the sera of 91% of the PCM
      patients studied. No cross reactions were observed with sera from patients with
      other systemic mycoses. Presently we are sequencing and characterizing this
      clone, in order to design specific primers for amplification of Pb DNA.

PMID- 8580686
TI  - Molecular Phylogenetic classification of fungi.
AB  - Phylogenetic classification of fungi based on comparison of ribosomal RNA gene
      sequences is discussed with emphasis on (i) the place of fungi in all of life,
      (ii) the relationship of medically important fungi to other fungi including model
      organisms and, (iii) the integration of sexual and asexual fungi into one
      classification.

PMID- 8580687
TI  - Molecular and genetic control of chitin biosynthesis in fungi.
AB  - Chitin is the most important structural component of the cell walls of fungi. Its
      synthesis involves the transfer of N-acetylglucosaminyl residues from the
      universal donor UDPGlcNAC to the growing chain. This reaction is catalyzed by an
      ill-defined enzyme called chitin synthetase. By use of diverse techniques,
      including reverse genetics, it has been possible to isolate mutants affected in
      chitin biosynthesis in vitro and in vivo. These studies have permitted the
      identification of several genes that code for the catalytic components of the
      enzyme, and probably for ancillary reactions. In general, two types of genes have
      been identified in fungi. The so-called CHS genes, from which two families, and
      possibly three classes exist, code for chitin synthetases activated by proteases.
      All fungi thus far studied contain more than one CHS gene, which are normally
      dispensable. The second class are larger, essential genes coding for the
      catalytic polypeptide of chitin synthetases non-activated by proteolysis, and
      probably made of more than one polypeptide. These are labeled CSD2 or CAL1. It
      may be hoped that our knowledge of chitin synthetase will make them the most
      suitable targets for new strategies to control fungal infections.

PMID- 8580688
TI  - [Effects of Shenmai injection on immune function in stomach cancer patients after
      chemotherapy].
AB  - Sixty-three cases with stomach cancer were randomized and observed, the results
      showed that the count of T lymphocytes in chemotherapy combined with Shenmai
      injection (SMI) group increased, while in control group it decreased, the
      difference was significant (P < 0.05). The results also indicated that the count
      of OKT4 cells and the ratio of OKT4/OKT8 decreased after chemotherapy, but in SMI
      group both parameters increased in advence which were higher in the 4th week
      after chemotherapy than that before chemotherapy. However, the count of OKT1
      cells and the ratio of OKT4/OKT8 were still in low level. Serum interleukin-2
      receptor (sIL-2R) level also decreased (P < 0.05), while activities of natural
      killer cell (NK) and lymphokine activated killer cell (LAK) level increased (P <
      0.05) in SMI group. Although the sIL-2R level had no change, both NK and LAK
      level decreased in control group. In addition, the difference of IgA, IgM, IgG
      level were not significant between these two groups. This suggested that SMI
      might improve human immune function to facilitate the chemotherapy of patients
      with stomach cancer.

PMID- 8580689
TI  - [Effect of qigong on heart-qi deficiency and blood stasis type of hypertension
      and its mechanism].
AB  - Comparative study was performed on the Heart-Qi Deficiency and Blood Stasis type
      (HQDBS) of hypertensive patients treated with Qigong. The results showed that the
      clinical symptoms alleviated, cardiac morphology and function, hemorheology and
      erythrocyte deformity were improved. After one year of practicing Qigong, plasma
      histofibrinogen activation inhibitor (PAI) and VIII factor related antigen (VIII
      R: Ag) levels decreased, while plasma tissue fibrinolytic activator (t-PA) and
      anti-thrombogen III (AT-III) levels increased. Capillary blood velocity of
      nailfold microcirculation raised from 0.2940 +/- 0.0206 mm/s to 0.3045 +/- 0.0236
      mm/s, the diameter and length of afferent limb tended to increase. The above data
      indicated that Qigong could benefit HQDBS. This might be the mechanism by which
      HQDBS type of hypertension was treated.

PMID- 8580690
TI  - [Clinical study on early use of Chinese medicinal herbs and chemotherapy after
      operation of gastric cancer].
AB  - In order to study the efficacy of early chemotherapy after operation of gastric
      cancer, 84 cases of gastric cancer were divided randomly into two groups. The
      treated group received both Chinese medicinal herbs and chemotherapy on the first
      postoperational day and the control group were treated routinely in the same way
      two weeks later. The results showed that complications of incision and
      anastomoses of the treated group did not rise and all kinds of blood cells reduce
      in comparison with those of control group (P > 0.05). Meanwhile, nutritious
      condition of the treated group was improved significantly as compared with that
      of control group (P < 0.05) because of use of Chinese medicinal herbs and
      nutrition support. This study suggested that chemotherapy could be used early
      after operation of gastric cancer in combination with Chinese medicinal herbs.

PMID- 8580692
TI  - [Clinical and experimental study on inhibitory effect of sanhuang mixture on
      platelet aggregation].
AB  - Sanhuang mixture (Xinmai capsule) is composed of Astragalus membranaceus, Coptis
      chinensis and Scutellaria baicalensis. It could inhibit platelet aggregation
      (PAG) induced by ADP in rats or by ADP and ADR in vivo. Patients with high PAG
      took Xinmai capsule for 4 weeks, the effective rate was 88.7%, which was same as
      the efficacy of aspirin 50 mg/day. In Syndrome Differentiation of TCM, the
      effective rate was the highest (92.3%) in the Syndrome of Qi Deficiency-Blood
      Stasis, and the lowest (72.7%) in the Syndrome of Stasis Phlegm and combined
      together.

PMID- 8580691
TI  - [Treatment of leucopenia with pure Astragalus preparation--an analysis of 115
      leucopenic cases].
AB  - This article reports the effects of pure Astragalus preparation (PAP) in treating
      115 cases of leucopenia. These cases were randomized and divided into two groups.
      Group I (58 cases) was treated by more concentrated PAP (every 10 ml equalled to
      15 grams of Astragalus), Group II (57 cases) was treated by less concentrated PAP
      (every 10 ml equalled to 5 grams of Astragalus). The patients took the PAP twice
      a day, 10 ml each time. The course of treatment was 8 weeks for both groups. The
      results showed that effectiveness in Group I was 82.76%, while in Group II
      47.37%, with a total effective rate of 65.22%, they were statistically different
      (P < 0.01). According to the comparison of average WBC counts after treatment,
      Group I was significantly higher than that of Group II (P < 0.05). There was an
      obvious rise of the WBC counts in both groups after treatment (P < 0.001). The
      results were dose-dependent. The author holds that Astragalus is an effective
      drug in treating leucopenia, and increasing the dosage could enhance its
      effectiveness.

PMID- 8580693
TI  - [Clinical study of effect of zhengda zhenhua 851-R oral liquor on delayed aging
      process].
AB  - A study was conducted on the effects of Zhengda Zhenhua 851-R (ZZ-851-R) oral
      liquor on middle aged-old patients with Kidney and Spleen Deficiencies. It was
      found that ZZ-851-R was able to relieve the symptoms of aging, improve the memory
      and fluency of speech, the activity of superoxide dismutase (SOD) GSH and GSH
      peroxidase (GSH-Px) increased remarkably and serum lipid peroxide (LPO) level
      decreased significantly. Improvements of immunity, function of the pituitary
      gonad axis were also noticed in the study, with decreased E2/T ratio and improved
      ability of total antioxydation. In summary, the ZZ-851-R has the effect of
      antisenility, without obvious side-effect.

PMID- 8580694
TI  - [Comparative study of diagnostic standards of eye-signs in blood stasis syndrome
      and of blood stasis syndrome].
AB  - By virtue of a diagnostic study of 781 cases on the basis of six standards, it
      was shown that for the effectiveness in diagnostic positive rate, sensitivity,
      specificity, false positive rate, false negative rate and comprehensive scoring,
      the International Diagnostic Standards for Blood Stasis Syndrome (BSS) and
      Chinese Diagnostic Standards for BSS were the best ones, BSS Eye-Signs and
      Japanese BSS Diagnostic Standards were the second, trial program of International
      Stasis Diagnostic Standards and Zhongshan's BSS tenderness points came the third.
      Each standard has its unique advantage and therefore, we should take the other's
      advantage to offset one's weakness. The causes of their weakness have been
      discussed and the rational recommendation for their application has been
      proposed.

PMID- 8580695
TI  - [Effect of Jinshuibao capsule on the immunological function of 36 patients with
      advanced cancer].
AB  - Jinshuibao Capsule (JSBC), produced by Jiangxi Jinshuibao pharmaceutical Company
      Limited, possesses the similar active principles and pharmacological activity
      with those of Cordyceps sinensis. The effect of JSBC on the immunological
      function of 36 patients with advanced cancer showed that it could restore
      cellular immunological function, improve quality of life, but had no significant
      effect on humoral immunological function. The results suggested that JSBC could
      be used as adjuvant drug in advanced cancer.

PMID- 8580696
TI  - [Experimental study on anti-atherosclerotic effect of tongmai jiangzhi oral
      liquor].
AB  - 27 Japanese white male rabbits were divided into 3 groups for evaluation of
      Tongmai Jiangzhi Oral Liquor (TMJZ) in reducing the serum cholesterol, the level
      of plasma lipid peroxidation (LPO), the plasma TXB2 and suppressing of
      atherosclerotic plaque formation in atherogenesis. The results indicated that
      TMJZ not only decreased significantly the levels of serum cholesterol,
      triglyceride, LPO and TXB2, but also increased markedly blood glutathion
      peroxidase (GSH-Px) activity and regulated the balance of TXB2/6-keto-PGF1 alpha.
      The area of atherosclerotic plaque coverage in aorta and the thickness of plaque
      after oral TMJZ were much smaller than those of high cholesterol-fed rabbits. It
      is suggested that the effect of TMJZ on above-mentioned indexes might be
      important mechanism of its anti-atherosclerotic effect.

PMID- 8580697
TI  - [Effect of Astragalus membranaceus on Ca2+ influx and coxsackie virus B3 RNA
      replication in cultured neonatal rat heart cells].
AB  - The effect of Astragalus membranaceus (AM) on Ca2+ influx across the myocardial
      plasma membrane and coxsackie virus B3(CVB3)-RNA replication in cultured neonatal
      rat heart cells infected with CVB3 was investigated. It was found that the Ca2+
      influx could be inhibited significantly (P < 0.01) by AM after infection of heart
      cells for 48 h. In addition, when the cultured heart cells infected with CVB3 and
      treated with AM for 48 h, the Ca2+ influx of infected heart cells also could be
      inhibited by AM (P < 0.05) and the amounts of CVB3-RNA in myocytes were
      significantly decreased than that in infected control group (P < 0.001). These
      phenomena suggested that AM could exert the effects of decreasing the secondary
      Ca2+ damages, and improving the abnormal myocardial electric activity, and
      inhibiting replication of CVB3-RNA in myocardium. Thus, it is a rational choice
      to treat patients with AM in viral myocarditis.

PMID- 8580698
TI  - [Protective effects of Angelica sinensis injection on myocardial
      ischemia/reperfusion injury in rabbits].
AB  - The injection of aqueous extract of Angelica sinensis (AS), 50 mg/kg, 30 ml, were
      administered intravenously at a rate of 0.4 ml/min by an infusion pump 10 min
      before the left anterior descending coronary artery of rabbit was ligated, the
      LVP and +/- dp/dtmax of the rabbit heart injured by ischemia/reperfusion in vivo,
      were significantly higher than those in the control group (N.S. group, P < 0.05
      0.01), and the level of malon-dialdehyde (MDA) and the activity of creatine
      phosphokinase (CPK) in the blood plasma were lower than those in the control
      group remarkably (P < 0.05-0.01). These results showed that AS exerted obvious
      protective effects on myocardial dysfunction and myocardial injury induced by
      ischemia/reperfusion.

PMID- 8580699
TI  - [Progress on research of mechanism of Rheum palmatum in delaying the chronic
      renal failure].

PMID- 8580700
TI  - [Progress on research in preventing and treating the myocardial
      ischemia/reperfussion injury with Chinese herb medicine].

PMID- 8580701
TI  - Symposium on Miniaturisation in Liquid Chromatography versus Capillary
      Electrophoresis. Ghent, Belgium, 23 May 1995. Abstracts.

PMID- 8580702
TI  - Chiral separation of naphthalene-2,3-dialdehyde labelled peptides by cyclodextrin
      modified electrokinetic chromatography.
AB  - The chiral separation of several dipeptide enantiomers, derivatized by
      naphthalene-2,3-dialdehyde (NDA), was achieved by use of cyclodextrin-modified
      micellar electrokinetic chromatography (CD-MEKC). The dipeptides contained one or
      two chiral centers. In the case of several dipeptides containing two chiral
      centers, all four of the optical isomers could be separated and baseline resolved
      in less than 15 min with 20 mM gamma-CD and 50 mM sodium dodecyl sulphate (SDS)
      in the background electrolyte. The order of elution of these derivatized
      dipeptides was explained by considering important chemical equilibria in the SDS,
      CD and peptide system. Additionally, the influence of geometric location of the
      chiral center, the structure of the side-chain and the effect of CD concentration
      on the resolution are discussed.

PMID- 8580703
TI  - Rapid determination of O- and P-cresol isomers in urine from workers exposed to
      toluene by high-performance liquid chromatography using a graphitized carbon
      column.
AB  - A simple and rapid procedure is described that permits the simultaneous
      determination of o- and p-cresol in urine of workers of other individuals exposed
      to toluene. The urine samples are enzymatically hydrolysed and analysed by high
      performance liquid-chromatography with a detection limit of 0.2 mg/L, one fifth
      of the biological threshold limit value for o-cresol (1 mg/g), a specific marker
      of toluene exposure. A graphitized carbon column Hybercarb-S, that exhibits an
      excellent selectivity for aromatic positional isomers, was used with 1%
      phosphoric acid-acetonitrile (70:30, v/v) as mobile phase and a detection
      wavelength of 271 nm. The overall accuracy for o-cresol determination was 4.5% at
      5 mg/L and 8% at 0.5 mg/L. The cresol isomers were sufficiently resolved from
      endogenous materials to avoid the need for any extraction step, and the method
      appears suitable for monitoring workers accurately under the permissible level of
      exposure for occupational medicine purpose.

PMID- 8580704
TI  - Determination of unbound L-tryptophan in human plasma using high-performance
      liquid chromatography with fluorescence detection.
AB  - An assay for the measurement of unbound L-tryptophan concentrations in plasma was
      developed using reverse-phase HPLC with fluorescence detection. Unbound L
      tryptophan from plasma was obtained using the Amicon MPS-1 ultrafiltration
      device. L-tryptophan binding to the membrane in the ultrafiltration device was
      not significant. A linear relationship between the peak-area ratios (peak-area of
      L-tryptophan to internal standard) and concentrations of L-tryptophan was
      obtained in the range of 0.1 microgram/mL to 2.5 micrograms/mL. The intra-assay
      precision was less than 10% for each control (0.18 microgram/mL, 0.75
      microgram/mL and 2.0 micrograms/mL). The inter-assay precision was less than 15%
      for each control; the accuracy for each control; the accuracy for each control,
      expressed as percent difference from nominal (%DFN), was less than 12%. This
      method was used to determine unbound L-tryptophan concentrations in plasma from
      nine male subjects who participated in a clinical study.

PMID- 8580705
TI  - Biochemical and functional diversity of microtubule motors in the nervous system.
AB  - The fact that multiple microtubule-based motors exist in brain inevitably raises
      questions about their function. Transcripts for at least seven kinesin
      superfamily genes and even more dynein heavy chain genes have been detected in
      brain cDNA libraries. The challenge now is to match their gene products to
      specific functions in cells of the nervous system. Recent studies have attempted
      to establish a function for each microtubule motor by using recombinant protein
      and immunochemical approaches.

PMID- 8580706
TI  - The function of dynamin in endocytosis.
AB  - Temperature-sensitive shibire mutants of Drosophila melanogaster become rapidly
      paralyzed upon a shift to the restrictive temperature, which is due to a block in
      synaptic vesicle endocytosis. The shibire gene encodes the GTPase dynamin. Recent
      studies have shown that dynamin forms rings at the neck of invaginated clathrin
      coated pits, and have suggested that a conformational change in the ring, which
      correlates with GTP hydrolysis, plays an essential role in vesicle fission.

PMID- 8580707
TI  - Silencing is golden: negative regulation in the control of neuronal gene
      transcription.
AB  - Recent work has identified negative-acting DNA regulatory elements that function
      to prevent the expression of neuronal genes in non-neuronal cell types or in
      inappropriate neuronal subtypes. In some cases, the protein factors that interact
      with these silencer elements have been isolated and characterized. For example,
      the recently cloned silencer-binding factor NRSF/REST is a novel zinc-finger
      protein that interacts with silencer elements in a number of neuron-specific
      genes. These data suggest that negative regulation plays a major role in
      determining the diverse patterns of gene expression within the nervous system.

PMID- 8580708
TI  - The GAL4 system as a tool for unravelling the mysteries of the Drosophila nervous
      system.
AB  - The GAL4 system is a method for directed gene expression that allows genes to be
      expressed ectopically in numerous cell- or tissue-specific patterns. The
      technique is being exploited to study the Drosophila melanogaster nervous system
      at all stages of development, from the embryo to the adult. The GAL4 system is
      being used to target the expression of novel marker genes in living animals to
      label cells, or subcellular structures. Directed expression of toxin genes can be
      used as a method for targeted cell ablation to study the role of cell-cell
      interactions in development. Ectopic expression helps to elucidate the function
      of different genes in cell fate determination and differentiation, and is helping
      to define the regions of the brain involved in sexual behaviour.

PMID- 8580709
TI  - Early events in neurotrophin signalling via Trk and p75 receptors.
AB  - Biological responses to neurotrophins appear to be mediated by multiple
      signalling pathways. These emanate from, and are regulated by, the contributions
      of both Trk and p75 receptors. Early events in Trk signalling are becoming more
      clearly defined and point to cooperate interaction of both Ras-dependent and Ras
      independent pathways. Work over the past year has clarified the steps by which
      Trk receptor occupation leads to Ras activation and has highlighted the required
      roles of Ras and extracellular signal regulated kinases in certain neurotrophin
      responses, including neurite outgrowth. Pharmacologic and mutagenesis studies
      have additionally supported the importance of the phosphatidylinositol-3' kinase
      and SNT protein pathways in neurotrophin signalling. Although many findings point
      to clear involvement for p75 in neurotrophin signalling, the molecular mechanisms
      by which these occur are just beginning to be identified. Recent studies indicate
      that p75 dramatically influences Trk activity and ligand interactions, and may
      mediate signals through the ceramide second-messenger pathway.

PMID- 8580710
TI  - Myelin-associated glycoprotein: a role in myelination and in the inhibition of
      axonal regeneration?
AB  - Inhibitory molecules in CNS myelin affect axonal regeneration after injury. In
      the past year, myelin-associated glycoprotein (MAG), a well-characterized myelin
      protein, has been identified as an inhibitor of axonal regeneration. This
      finding, together with its established ability to promote outgrowth, defines MAG
      as a bifunctional molecule. MAG has also been included in a family of sialic acid
      binding proteins, providing a clue to the identity of the MAG receptor. MAG
      knockout mice reveal that MAG is not essential for the initiation of myelination;
      however, it plays an important role in maintaining a stable interaction between
      axons and myelin.

PMID- 8580711
TI  - The basement membrane at the neuromuscular junction: a synaptic mediatrix.
AB  - The basement membrane at the neuromuscular junction directs formation of pre- and
      postsynaptic elements at this synapse. Efforts to understand the molecular basis
      for development of the postsynaptic specialization have brought new insights into
      extracellular matrix proteins and their cell-surface receptors. Recent evidence
      for an agrin receptor and mice null for the s-laminin gene have reinforced the
      function of the basement membrane in both orthograde and retrograde signalling
      across the synapse.

PMID- 8580712
TI  - Neuregulins and their receptors.
AB  - The recent identification of an activator for the ErbB2/Neu receptor has
      uncovered a new family of polypeptide growth factors that undoubtedly play a
      major role in the regulation of neuronal growth and differentiation. These
      factors, called the neuregulins, are expressed in neural and mesenchymal tissues,
      and activate members of the epidermal growth factor family of receptor tyrosine
      kinases. The identification and characterization of the neuregulins and their
      receptors will facilitate the dissection of the biochemical pathways regulating
      nervous system development.

PMID- 8580713
TI  - Peripheral neuropathies and neurotrophic factors: animal models and clinical
      perspectives.
AB  - A large body of data exists showing that a wide variety of neurotrophic factors
      can promote the survival or growth of different neuronal populations in vitro.
      More recently, several studies have been published on the survival-promoting
      effects of particular factors in animal models of peripheral neuropathies. Thus,
      the effect of axotomy on neuropeptide expression in dorsal root ganglion cells is
      partially reversed by nerve growth factor treatment, and the effect on choline
      acetyltransferase expression in motoneurones is partially reversed by glial
      derived neurotrophic factor, neurotrophin-4/5 and brain-derived neurotrophic
      factor. Nerve growth factor also ameliorates some of the changes seen in sensory
      neurones in animal models of diabetic neuropathy and small fibre cytostatic drug
      neuropathy, whereas neurotrophin-3 has been found to reverse some changes in
      large sensory neurones associated with cisplatin neurotoxicity. The results of
      these studies provide grounds for optimism in the clinical uses of such factors,
      and, indeed, several clinical studies are now under way.

PMID- 8580714
TI  - Regeneration in the adult mammalian CNS: guided by development.
AB  - In the past year, the roles and mechanisms of molecules involved in cell survival
      (glial-derived neurotrophic growth factor), growth cone guidance (netrins and
      semaphorins), axonal outgrowth and sorting (neural cadherin, polysialylated
      neural cell adhesion molecules, and L1), and neuronal connectivity (cell adhesion
      molecules, dystroglycan, and agrin) have been described during development and,
      to a limited extent, in the mature CNS. Evidence is now emerging that some
      developmental events, such as the expression of polysialylated neural cell
      adhesion molecule and L1, are recapitulated during adult CNS regeneration. These
      results suggest new avenues to address more accurately the challenges of axonal
      regrowth in the adult mammalian CNS.

PMID- 8580716
TI  - Cytokines in Alzheimer's disease and multiple sclerosis.
AB  - Cytokines are well known as mediators of inflammation, and recent work has
      highlighted the role of these agents and inflammatory events in Alzheimer's
      disease and multiple sclerosis. The discovery of subclasses of T-helper cells has
      provided a critical framework to aid in understanding how the cytokine network
      regulates these diseases.

PMID- 8580715
TI  - Inflammation in the nervous system.
AB  - Earlier studies on inflammation in the CNS have largely focused on conditions
      with an immune component. Recent evidence has emerged, however, that the innate,
      acute inflammatory response in the CNS parenchyma is quite unlike that in other
      tissues. The meninges and ventricular compartments show more typical responses,
      as does the parenchyma of the brain in immature animals. It is becoming apparent
      that the cells of the mononuclear phagocyte lineage dominate inflammatory
      responses in the CNS parenchyma.

PMID- 8580717
TI  - HIV interactions with cells of the nervous system.
AB  - HIV can invade the CNS, where it replicates principally in macrophages. Yet,
      neurological disease is more often correlated with levels of neurotoxins or tumor
      necrosis factor alpha than with viral replication or specific viral determinants
      in brain. In experimental systems, HIV glycoprotein affects functions of
      uninfected microglia and astrocytes to eventually cause neuronal death. While the
      cellular basis of cognitive and neurological dysfunction are unravelled in the
      simian immunodeficiency virus model, the molecular mechanisms of HIV
      neurotoxicity are being studied in newly developed mouse models.

PMID- 8580718
TI  - Huntington's disease: CAG genetics expands neurobiology.
AB  - Huntington's disease, with its progressive uncontrolled movements and
      characteristic selective neuropathology, has represented a baffling enigma to
      geneticists and neurobiologists alike. Discovery of the HD gene and its defect
      has demystified the genetic aspects of the disorder, but has not yet explained
      its pathogenesis. Attempts to explore this issue suggest that the defect acts as
      a gain of function, conferring a new deleterious property on the huntingtin
      protein, and that the gene's normal function may be irrelevant to the disease
      process.

PMID- 8580719
TI  - Disruption of the cytoskeleton in Alzheimer's disease.
AB  - Paired helical filaments (PHFs) in Alzheimer's disease are formed from
      hyperphosphorylated brain tau known as PHF-tau. Many sites of phosphorylation
      that were thought to be present only in PHF-tau are now known to be normal
      phosphate acceptor sites in both fetal and rapidly processed adult brain tau. The
      rapid dephosphorylation of normal brain tau by protein phosphatases 2A and 2B
      provides an explanation for the apparent absence of phosphates at these sites in
      the normal adult brain tau obtained postmortem. Although the functional
      significance of each of these normal phosphate acceptor sites is unknown at this
      time, emerging evidence suggests that the binding of tau to microtubules is
      regulated by the simultaneous phosphorylation and dephosphorylation of tau at
      multiple sites.

PMID- 8580721
TI  - Neuronal and glial cell biology.

PMID- 8580720
TI  - CNS genetic disorders: loss of function, gain of function, or something else?

PMID- 8580722
TI  - Disease, transplantation and regeneration.

PMID- 8580723
TI  - Neuromuscular disorders: gene location.

PMID- 8580724
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 8580726
TI  - How does dystrophin deficiency lead to muscle degeneration?--evidence from the
      mdx mouse.
AB  - The mdx mouse has a defect in the same gene as boys with Duchenne muscular
      dystrophy, which results in the absence of the protein product, dystrophin. A
      large number of recent studies have used the mdx mouse model to examine the
      potential role of dystrophy in normal muscle and the mechanisms by which
      dystrophin-deficiency leads to myopathy. This review discusses critically the
      results of these studies and their relevance to understanding the mechanisms by
      which dystrophin-deficiency leads to muscle necrosis.

PMID- 8580725
TI  - A gene for autosomal recessive nemaline myopathy assigned to chromosome 2q by
      linkage analysis.
AB  - Clinical genetic evidence suggests the existence of an autosomal recessive form
      of congenital nemaline myopathy in addition to the autosomal dominant one(s). One
      mutation in an Australian kindred has been identified as causing an autosomal
      dominant form of the disease. This mutation in the alpha-tropomyosin gene TPM3
      has previously been excluded as causing autosomal recessive nemaline myopathy. We
      searched systematically for genetic linkage to autosomal recessive nemaline
      myopathy (NEM2) by studying microsatellite marker alleles in seven multiplex
      families from Finland, Denmark, Wales, England and The Netherlands. Significant
      evidence of linkage was found to markers of chromosome 2q, the highest multipoint
      lod score value being 5.34 for the marker D2S151. Recombinant genotypes in
      affected individuals demarcate the the region in which the NEM2 gene is likely to
      reside as a 13 cM region between the markers D2S150 and D2S142. These results
      confirm the existence of at least one distinctive form of autosomal recessive
      nemaline myopathy and provide a basis for the identification of its gene.

PMID- 8580727
TI  - Search for persistent infection with poliovirus or other enteroviruses in
      amyotrophic lateral sclerosis-motor neurone disease.
AB  - A longstanding hypothesis proposes that amyotrophic lateral sclerosis-motor
      neurone disease (ALS-MND) is a late consequence of subclinical poliovirus (PV)
      infection. In this study, RNA extracts of CNS tissue from 28 patients with ALS
      MND and 7 controls were assayed by nested polymerase chain reaction (PCR) using
      primers to the 5'-untranslated region (UTR) of the enterovirus (EV) genome which
      is highly conserved between EVs including PV, echovirus and coxsackie viruses.
      The integrity of RNA extracted from either archival paraffin-embedded or frozen
      CNS tissue was assessed by detection of constitutive Ableson tyrosine kinase
      (ABL) mRNA by PCR. Of 63 tissue samples assayed, 81% (51/63) were ABL-positive
      corresponding to 78% (22/28) of the ALS-MND cases and all controls. None of the
      27 ALS-MND cases (i.e. 21 ABL+ and 6 ABL-) in which paraffin-embedded tissue was
      used nor any of the age and sex matched controls were positive for specific PV/EV
      RNA. Moreover, CNS tissue from 14 different locations obtained from one patient <
      2 hrs after death and immediately frozen, showed no evidence of PV/EV at any site
      by PCR. Disease duration, degree of tissue autolysis and duration of tissue
      storage were all excluded as factors which may predispose to negative results.
      The sensitivity of the PV PCR was determined to be 40-400 copies (12.5 - 125 ag)
      of synthetic EV RNA transcripts in 1 microgram of cellular RNA and the assay was
      shown to detect all types of PV and and other EVs tested. Thus it seems unlikely
      that a persistent PV or related EV infection is implicated in ALS-MND unless
      there has been alteration in the 5'-UTR of the virus genome.

PMID- 8580728
TI  - Abnormal expression of heparin sulfate proteoglycan on basal lamina of muscle
      fibers in two Japanese patients with adhalin deficiency.
AB  - We recently reported the selective reduction of the B1 subunit of laminin in two
      Japanese patients with adhalin deficiency. We here investigated
      immunohistochemically the expression of other components of the extracellular
      matrix (ECM), including collagen type IV, heparan sulfate proteoglycan can
      (HSPG), chondroitin-4-sulfate proteoglycan, decorin, and fibronectin in adhalin
      deficiency, compared with other types of muscular dystrophy. We found a reduction
      of HSPG on the basal lamina surrounding each muscle fiber in adhalin deficiency
      compared with HSPG in other diseases. This finding may be characteristic evidence
      of the disturbance of the sarcolemma-ECM interaction and the sarcolemmal
      instability in adhalin deficiency. Recently, a direct role of HSPG in fibroblast
      growth factor (FGF) signal transduction was demonstrated. Further investigation
      is required to determine if the dysfunction of FGF is relevant to the
      pathogenesis of adhalin deficiency.

PMID- 8580729
TI  - Duplication of dystrophin gene and dissimilar clinical phenotype in the same
      family.
AB  - We report here three related patients with a duplication of exons 19-41 of the
      dystrophin gene, having dissimilar clinical phenotype and dystrophin
      immunohistochemistry. Two brothers aged six and three years had myalgia, proximal
      muscular weakness and hypertrophic calves, with 10- 20-fold increase of serum
      creatine kinase. Muscle biopsy showed dystrophic changes and reduced, patchy
      binding of dystrophin. The clinical and laboratory findings were consistent with
      a diagnosis of Becker muscular dystrophy with early onset. Their 14-year-old
      cousin had only mild hyperCKemia. His muscle biopsy was normal with only mild
      reduction of dystrophin immunostaining. At follow-up, he is still without
      symptoms and signs at age 19. All three patients had the same gene duplication
      and an increased dystrophin size of 507 kDa. Expression of the dystrophin
      associated glycoproteins adhalin, alpha-dystroglycan, and beta-dystroglycan were
      normal in the three patients. An intrafamilial variability in patients carrying a
      partial duplication of the dystrophin gene may be related to a quantitative
      difference in mRNA.

PMID- 8580730
TI  - The 8,344 mutation in mitochondrial DNA: a comparison between the proportion of
      mutant DNA and clinico-pathologic findings.
AB  - Ten patients, two men and eight women with mitochondrial encephalomyopathy, had
      an A-G mutation at nucleotide pair 8,344 in the mitochondrial DNA, the most
      common genetic defect in myoclonus epilepsy with ragged-red fibers (MERRF). Eight
      patients had the clinical and pathologic characteristics of MERRF including
      myoclonus, seizures, cerebellar ataxia and myopathy with ragged-red fibers. Two
      patients had atypical symptoms such as early onset of fatal cardiac failure and
      late onset of rapid mental deterioration, respectively. The striking feature in
      our patients with the 8,344 mutation cardiac involvement and two developed
      progressive heart failure. In the typical MERRF patients, the proportion of
      mutant mitochondrial DNA in their skeletal muscles, quantified by a single strand
      conformation polymorphism analysis, was above 85%. However, there was no
      significant correlation between clinical severity, histopathological findings and
      the proportion of mutant mtDNA in muscle biopsy samples, suggesting that non
      ragged-red fibers play an important role in the phenotype expression of the
      mutants.